HUMAN PHYSIOLOGY

MACMILLAN AND CO., LIMITED

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V-

V

- ' HUMAN" "".,f
PHYSIOLOGY

BY

PROFESSOR LUIGI LUCIANI

DIRECTOR OF THE PHYSIOLOGICAL INSTITUTE OF THE ROYAL UNIVERSITY OF ROMK

TRANSLATED BY

FRANCES A. WELBY

EDITED BY

DR M. CAMIS

INSTITUTE OF PHYSIOLOGY, UNIVERSITY OF PISA

WITH A PREFACE BY

J. N. LANGLEY, F.RS.

PROFESSOR OF PHYSIOLOGY IN THE UNIVERSITY OF CAMBRIDGE

IN FOUR VOLUMES
VOL. I.— CIRCULATION AND RESPIRATION

MACMILLAN AND CO., LIMITED

ST. MARTIN'S STREET, LONDON

1911

PREFACE

" GOOD wine needs no bush," but it will perhaps not be an in-
fringement of this maxim to introduce, in a few words, Professor
Luciani's excellent Text-Book of Physiology to the English-reading
public. The Italian Text-book is now in its third edition, the
final pages being in the Press. One or other of the earlier editions
has been translated into French, German, and Eussian, and it is
a matter for surprise that we have had to wait so long for an
English version.

In the making of physiological text -books, we are at the
parting of the ways. The physiologists of the past generation
were brought up to know with familiarity all that had been
recently done in physiological research, whether in vertebrates or
invertebrates, in animals or in plants. The facts were not so
numerous that they could not be stored in the memory without
cumbering the judgment, and Physiologists could in some sort
be first-hand authorities on all branches of the subject. That
condition has been gradually passing away, and it is hardly
possible for any one who is not of the old school to write an
advanced text-book covering the whole ground of Physiology.
Thus the text-book of single authorship is giving way to the
text-book of multiple authorship. The latter, whatever its merits,
has not the unity of view and the sense of proportion which
belong to the former — qualities very important in a book intended
for students.

Professor Luciani's book, whilst describing phenomena with
considerable detail, treats lucidly the broad principles to be
deduced from them. It stands midway between the text-book
which confines itself to summing up the results of physiological
investigation, and that which gives also a minute historical
account of the progress of investigation. It deals with the main

vi PHYSIOLOGY

outlines of the history of each branch of the subject, but does not
allow this to interfere with the even flow of narration.

It is natural that writers of Text-books should make frequent
reference to the work that has been done by their own country-
men. Italian work is less widely known than it deserves, and
one of the advantages of this book for English-speaking folk is
that Italian workers receive their meed of notice. It will, how-
ever, be a shock to many English readers to find that Professor
Luciani allots the discovery of the systemic circulation of the
blood to his countryman, Cesalpinus. That the circulation of the
blood was described and demonstrated by Harvey, no one doubts..
That there were a number of forerunners of Harvey who under-
stood this or that important fact connected with the circulation is
equally undoubted. In considering the place to be assigned to
each of those who helped to solve the problem, two separate
questions arise. First, How far are the facts and views original
and not obtained from unacknowledged sources ? and secondly,
What was the exact degree of understanding of the subject
possessed by each writer ? It may seem that the former question
only would be difficult to solve. In fact, the difficulty of the
latter is no less, or at any rate differences of opinion with regard
to it have not been less ardent ; and so we find that whilst most,
authorities regard Cesalpinus as having but imperfectly compre-
hended the systemic Circulation, and to have seen it " darkly
through Galenical glasses," some, as Professor Luciani, consider
that his comprehension was whole and without flaw.

Finally, it may be noted that the Editor, Dr. Camis, has
added at the end of each chapter a selected list of English-written
Monographs and Papers, and thus has put the student who
knows no other language than English in the way of obtaining
a fuller knowledge of any branch of Physiology in which he may
be interested.

J. N. LANGLEY.

CAMBRIDGE, Jaw. 1911.

TRANSLATOR'S NOTE

I BEG to offer my sincere thanks to Dr. Aders-Plimmer
for his kind help in the translation of the chemical
section of this volume : and to Mr. W. L. Symes for
assistance in many other technical difficulties.

FRANCES A. WELBY.

LONDON, October 1910.

vii

>•

CONTENTS

PACK

INTRODUCTION . 1

1. Threefold division of biological science. 2. Special objects of
physiology. 3. Materialism, nee-vitalism, Ostwald's energetic monism,
Mach's psychical monism, pragmatic pluralism. 4. Physiology of
the cell ; general and comparative physiology ; human physiology.
Bibliography.

CHAPTER I

LIVING MATTER : ITS CHEMICAL AND PHYSICAL BASIS . .11

1. The cell-theory. 2. Morphology of the cell. 3. Structure of
protoplasm. 4. Structure of nucleus. 5. Chemical elements of the
cell. 6. Protein basis of living matter. 7. Classification of proteins.
8. Chemical constitution of proteins. 9. Enzymes or ferments. 10.
Classification. 11. Other nitrogenous organic substances, fats, carbo-
hydrates or saccharides, inorganic substances. 12. Chemical structure
of living matter. Bibliography.

CHAPTER II

LIVING MATTER : ITS FUNDAMENTAL PROPERTIES . . 42

1. Vital metabolism, and phenomena of nutrition and repro-
duction. 2. Vital metabolism and phenomena of excitability and
sensibility. 3. Laws of stability and variability of living species.
Critical examination of Theory of Evolution ; Darwinism, and Neo-
Lamarckism. 4. Evolutionary theories of Nageli, Weismann, De Vries.
5. Distinctive characters of plants and animals : (a} Doctrine of
Linnaeus ; (b) doctrine of Cuvier ; (c) doctrine of J. R. Mayer, Dumas,
Liebig. 6. Different forms of plant and animal metabolism : (a) Nitri-
fying bacteria ; (&) green plants ; (c) a-chlorophyllous plants ; (d)
herbivorous and carnivorous plants. Bibliography.

ix

x PHYSIOLOGY

CHAPTER III

PAGE

LIVING MATTER : CONDITIONS BY WHICH IT is DETERMINED . 64

1. Nutrition the necessary external condition of vital metabolism.
Phenomena of inanition. 2. Importance of water. Latent life and
anabiosis. 3. Importance of oxygen. Aerobic and anaerobic life. 4.
External temperature indispensable to life. 5. Total pressure of air
and water, and partial pressure of oxygen and carbonic acid. 6. Ex-
ternal stimuli. 7. Chemical stimuli. Chemotaxis. 8. Mechanical
stimuli. Barotaxis. 9. Thermal stimuli : thermotaxis. 10. Photic
stimuli. Phototaxis and Heliotaxis. 11. Electrical stimuli. Galvano-
taxis. 12. The various biological zones of ocean life (Plankton}. 13.
Internal conditions and stimuli of metabolism. Theory of automatism.
14. Hypotheses to explain the intimate mechanism of living matter.
Bibliography.

CHAPTER IV

THE BLOOD: FORMED CONSTITUENTS . . . .91

1. Arrangement of human physiology, aild classification of functions.
2. Importance of the blood as centre of the vegetative system and agent
of general metabolism. 3. Historical development of haematology.
4. General physico-chemical characters of the blood. 5. Estimation
of total quantity. 6. Physical and morphological characters of erythro-
cytes, and estimation of their relative quantity. 7. Chemical compo-
sition. Properties of haemoglobin and its derivatives. 8. Character,
composition, and physiological properties of leucocytes. 9. Blood
platelets, and elementary granulation of the blood. Bibliography.

CHAPTER V

THE BLOOD : PLASMA . . . . . .123

1. Different methods for separation of blood plasma from corpuscles.
2. Histogenic substances or proteins of plasma : fibrinogen, serum
globulin, serum albumin, sero - mucoid. 3. Nitrogenous histolytic
products of plasma. 4. Fatty substances. Carbohydrates and their
derivatives. 5. Inorganic substances. Blood gases. 6. Theory of
Coagulation : (a) Conditions of blood coagulation ; (b) disintegration
of corpuscles as cause of coagulation ; (c) fibrinogen as fibrin generator ;
(d) analogies between blood coagulation and curdling of milk ; (e) im-
portance of time in coagulation ; (/) thrombin and nucleins as coagu-
lating substances ; (g) histone and cytoglobulin as anti-coagulating
substances. 7. Osmotic pressure, molecular concentration, electrical
conductivity and viscosity of blood and serum. 8. Functions of the
blood : (a) effects of bleeding ; (b) effects of transfusion of homo- and
heterogeneous blood ; (c) bactericidal and immunising properties of
blood and serum. Bibliography.

CONTENTS xi

CHAPTER VI

PACK

THE CIRCULATION OF THE BLOOD : DISCOVERY . . .157

1. Physiological necessity for the circulation of the blood. Schema
of cardio-vascular system. 2. Theory of Galen. 3. Discovery of the
lesser circulation. Question of the priority of Columbus, Servetus,
and Vesalius. 4. Discovery of the general circulation by Cesalpinus.
5. Completion of the work by Harvey. 6. Discovery of the lymph
circulation by Eustachius, Aselli, Pecquet, Rudbeck, Bartholin. 7.
Discovery of the capillary system, and direct observation of the circu-
lation by Malpighi. 8. Microscopic observations of the phenomena of
circulation. Spallanzani, Poiseuille, R. Wagner, etc. 9. Discovery of
diapedesis of blood -corpuscles and migration of leucocytes : Waller,
Addison, Recklinghausen, Cohnheim. Bibliography.

CHAPTER VII

MECHANICS OF THE HEART . . . . .180

1. Description of cardiac cycle or revolution. 2. Changes of external
form, of the internal cavity, of the position and volume of the heart in
the different phases of its activity. 3. Mechanism of semilunar valves.
4. Mechanism of auriculo-ventricular valves. 5. Theory of so-called
heart -sounds. 6. Variations of pressure within the auricles and
ventricles during the cardiac cycle. 7. The diastolic aspiration ;
various explanatory hypotheses. 8. Cardiac plethysmograms ; theory
of active diastole. 9. Cardiograms ; theory of heart-beats or impulses.
10. Other mechanical effects of cardiac activity. 11. Work done by
the heart. Bibliography.

CHAPTER VIII

THE BLOOD-STREAM : MOVEMENT IN THE VESSELS . . .232

1. Fundamental laws of hydrodynamics for passage of fluid through
rigid tubes. 2. Application of these laws to haemodynamics. 3. Me-
chanical effects of elasticity of vessel-walls and intermittence of flow of
blood from heart ; laws of wave motion. 4. Method of measuring and
automatically registering variations in blood pressure. 5. Principal
results obtained. 6. Methods of measuring velocity of circulation ;
experimental results. 7. Sphygmography and sphygmograms repre-
senting pulsatory oscillations in pressure. 8. Comparison of cardio-
grams and sphygmograms registered simultaneously, indicating duration
of the principal phases of cardiac cycle in man. 9. Comparison of several
sphygmograms registered simultaneously from arteries at different
distances from the heart, indicating rate of transmission of primary
and of dicrotic wave. 10. Tachymetr-y and tachygrams representing
pulsatory variations in current velocity. 11. Pletliysmography and

xii PHYSIOLOGY

PAfi K

plethysmogranis representing pulsatory oscillations in the volume of the
arteries. 12. Schema of mechanical conditions of the circulation in the
three great vascular systems ; determination of duration of the entire
circulation. Bibliography.

CHAPTER IX

PHYSIOLOGY OF CARDIAC MUSCLE AND NERVES .285

1. Intrinsic processes by which cardiac rhythm is determined and
regulated. 2. Extrinsic chemical conditions of cardiac activity. 3.
Effects of ligation and section on different parts of the heart. 4.
Automatic or reflex activity of heart. 5. Myogenic or neurogenic
origin of cardiac rhythm. 6. Evidence for these conflicting theories.

7. Special mode in which cardiac muscle reacts to external stimuli.

8. Regulation of cardiac rhythm by nervous system ; inhibitory or
diastolic nerves. 9. Accelerator or systolic nerves. 10. Theory of
anabolic action of diastolic nerves and katabolic action of systolic
nerves. 11. Afferent nerves of heart or other parts of the body, which
influence cardiac rhythm. 12. Nerve centres for cardiac . nerves ;
their tonic excitability, and theory of regulation of cardiac rhythm.
Bibliography.

CHAPTER X

PHYSIOLOGY OF VASCULAR MUSCLE AND NERVES . . .341

1. Discovery of vasomotor nerves. 2. Vascular tone and its
rhythmic and a-rhythmical variations, as depending essentially upon
the automatic and reflex excitability of the smooth muscle cells. 3.
Theory of vaso-constrictor nerves. 4. Theory of vaso-dilator nerves.
5. Vascular reflexes. 6. Bulbar vaso-constrictor centre. 7. Spinal
and cerebral centres for vaso-constrictor nerves. 8. Centres for vaso-
dilator nerves. Bibliography.

CHAPTER XI

CHEMISTRY AND PHYSICS OF EESPIRATORY EXCHANGES . . 369

1. Early notions of the importance of respiration (Aristotle, Galen,
Leonardo da Vinci, van Helmont, Boyle, Hook, Fracassati, Lower,
Mayow). 2. Modern doctrines (Black, Bergmann, Priestley, Lavoisier).
3. Theory of gas exchanges in the lungs and tissues (Lagrange and
Spallanzani, W. Edwards). 4. Extraction of gases from the blood
(Magnus, L. Meyer, Hoppe - Seyler, Ludwig, Pfliiger). 5. Varying
content of arterial, venous, and asphyxiated blood. 6. State of the
oxygen in the blood. 7. State of the carbonic acid in the blood. 8.
Tension of gases in venous and arterial blood and in inspired and ex-
pired air ; theory of pulmonary gas exchange by diffusion and by
secretory processes. 9. Theory of gas exchanges in the tissues. 10.
The respiratory quotient and its variations. Bibliography.

CONTENTS

Xlll

CHAPTER XII

MECHANICS OF RESPIRATION . . .

1. Historical. 2. Glandular structure of the lungs. 3. Conditions
of the lungs and other viscera within the thorax ; passive movements
due to variations in the negative thoracic pressure. 4. The thoracic
cavity ; changes of form and dimensions with inspiratory and expiratory
movements. 5. Muscular mechanism of inspiratory and expiratory
movements. 6. Normal and forced respiration. 7. Accessory or con-
comitant respiratory movements. 8. Ventilation or renewal of pul-
monary air (spirometry), and respiratory pressure in the air -passages
(pneumatometry). 9. Respiratory displacement of the lungs, and
acoustic phenomena of percussion and auscultation. 10. Respiratory
variations of iiitrathoracic and intra-abdominal pressure. 11. Respira-
tory variations of pressure in the vena cava. 12. Respiratory variations
of aortic pressure. 13. Effect of respiratory mechanics on the circula-
tion of the blood. 14. Special forms of respiratory movements.
Bibliography.

CHAPTER XIII

THE NERVOUS CONTROL OF RESPIRATORY RHYTHM

1. Motor nerves to respiratory muscles and smooth muscle cells of
bronchi. 2. Bulbar respiratory centres and their localisation. 3. Spinal
respiratory centres. 4. Cerebral respiratory centres. 5. Each of these
centres results from the association of an inspiratory and an expiratory
centre, which function rhythmically and alternately. 6. Automatic
regulation of normal respiratory rhythm, by afferent pulmonary fibres
of vagus. 7. Influence exerted on respiratory rhythm via the cerebral
tracts and sensory nerves in general. 8. Phenomena consequent on
the separation of the bulb from the brain and spinal cord. 9. Dyspnoea
and its different forms. 10. Eupnoea or normal quiet respiration.

11. Experimental apnoea from artificial respiration with the bellows.

12. Foetal apnoea, and the analogous forms of experimental apnoea
that can be produced in the adult. 13. Voluntary, as compared with
experimental apnoea. 14. Apnoea produced by continuous ventilation
in birds. 15. Periodic respiration, or Cheyne - Stokes phenomenon.
16. Physiological theory of respiratory rhythm. Bibliography.

PAGE

402

440

CHAPTER XIV

THE LYMPH, AND INTERCHANGES BETWEEN THE BLOOD AND THE

TISSUES ... . 505

1. Structure of lymphatic vascular system, lymph spaces, sinuses
and cavities. 2. Origin ; physical, morphological and chemical charac-
teristics ; qualitative and quantitative variations of lymph. 3. Lymph-
atic circulation, and the various mechanical factors by which it is

xiv PHYSIOLOGY

determined. 4. Formation of lymph from the blood capillaries, and
the so-called lymphagogues. 5. Secretory theory of Heidenhain, and
transudation theory of Cohnheim. 6. Formation and modification of
lymph by the tissues. 7. Lymphoid tissue, follicles and lymphatic
glands. 8. Bone marrow. 9. The thymus. 10. The spleen.
Bibliography.

INDEX OF SUBJECTS . .561

INDEX OF AUTHORS 573

INTRODUCTION

1. Threefold division of biological science. 2. Special objects of physiology.
3. Materialism, neo- vitalism, Ostvvald's energetic monism, Mach's psychical monism,
pragmatic pluralism. 4. Physiology of the cell ; general and comparative
physiology ; human physiology. Bibliography.

THE remarkable development of Physiology during the nine-
teenth century justifies us in regarding it as one of the most
modern . sciences ; yet its origin is very ancient, and may be
traced back to the first flashes of philosophic thought. Through-
out the classical world, however, with few exceptions, the term
Physiology (according to its etymological signification) connotes
the philosophic study of Nature in general, i.e. it includes the
phenomena, not merely of living nature, but of inanimate nature
as well.

During the Middle Ages, again, until the Eenaissance, the
Science of Life is confounded with Philosophy, with Natural
History, with Medicine in general, and in particular with Anatomy.

In the second half of the eighteenth century the immense
progress made in the vast field of Natural History (so-called)
involved a corresponding division of labour. Intimate relations
obtain between mineralogy, geology, and physical geography.
These are complementary and reciprocal subjects, which are all
included among the inorganic natural sciences. Most intimate,
too, are the links connecting botany and zoology : " Between
plants and animals," as was happily said by Buffon, " there are
more common properties than real differences." Between dead and
living nature, however, the gap is far wider, the differences more
essential, and the study of the one may be undertaken independent
of the other.

At the commencement of the last century two eminent natural-
ists, Lamarck in France, and Treviranus in Germany, created the
word Biology, and applied it in the first instance to designate
the complex of closely related sciences which covers the phenomena
observed in living beings in general, i.e. in plants, animals, and
man.

VOL. II B

2 PHYSIOLOGY

But if Biology is to include the complete study of life in all
its manifestations, it represents a field too vast to admit of
comprehension by any single mind in all its details. Hence the
necessity arises for a further division of labour.

I. If at any given moment of its existence we set out to
consider the mode of life and action of any living being, we can at
once distinguish the morphological characteristics, depending ©n
anatomical and histological structure, from the functional or
physiological features, which are dependent on its cytological,
physical, and chemical constitution. If in living beings we
consider the development, the perpetual becoming, in other words
the morphological and physiological changes they undergo from
beginning to end of their existence, we have the story of
Evolution, which enables us to a certain point, both for the indi-
vidual and the species, to follow the different phases of development
as these fulfil themselves according to the great laws of heredity
and variation.

The complete study of life, to which the term Biology has thus
been applied, is appropriately divided into three branches : —

(a) Morphology, which covers the forms of living beings, i.e.
the cellular elements from which the tissues are built' up, the
connections of the tissues whence,, the organs develop, the
structure of the organs and systems.

(ft) Physiology, which covers the functions or activities of
living beings, and the various cytological, physical, and chemical
factors from which these arise : in other words, the storage and
dispersal of the energies of which organisms are the seat, and the
phenomena or external manifestations by which they are revealed
to us.

(c) Biogenesis, i.e. the story of evolution, morphological as well
as functional, whether ontogenetic, for the individual, or phylo-
genetic, for the race.

The intimate connections of these three great branches of
biological science are obvious. Since organic form is the necessary
matrix of function, the study of Physiology perforce includes that
of Morphology, or Anatomy — as the latter is commonly but loosely
termed. These two branches are really offshoots of the same
trunk, inasmuch as they constituted in bygone times a single
science professed by a single teacher, when the (vastly pre-
dominating) study of the morphological signs of life was identified
in various ways with that of its physiological properties. But as
the study of form has methods of research and problems which are
separate and quite distinct from those relating to function,
anatomy has gradually detached itself from physiology, pursuing
its own independent development. The History of Evolution or
Biogenesis, again, which covers a vast field of researches in em-
bryology, comparative anatomy, and palaeontology, is evidently

INTRODUCTION

an offshoot from the common trunk of Morphology and
In so far as it studies the development of forms it is intimately
related to morphology ; inasmuch as it investigates the develop-
ment of functions it is united by the closest bonds with physiology.

This threefold development of biology rests on no profound
scientific postulate, but merely arises from the convenience of a
division of labour, whether in fulfilment of a didactic necessity or in
order more rapidly to approach the ideal of a comprehensive know-
ledge of living phenomena. We may reasonably anticipate that
in proportion as the task assigned to each department approaches its
completion, and the corresponding methods of investigation are
exhausted, the relations will become more intimate, and the
intercourse between the workers in the three several fields more
frequent, till finally the great Science of Life, completed by all the
achievements of morphology, physiology, psychology, and natural
science, is reconstituted in its initial unity, as was predicted by
Lazzaro Spallanzani and Johannes Miiller.

Of late years the special province of Physiology has become
so vast that a considerable area of it is now set apart under the
name of Chemical Physiology, and it may seem as though we
were still very far from the synthetic reconstitution of Biology
as a unitary and well-organised science — an ideal image of the
living organism. Owing, however, to the aforesaid division of
labour, or to the undeniable exhaustion of certain superannuated
methods in other directions, General or Comparative Physiology,
an important department which was too much neglected in the
past, has been developed and perfected ; this comprises the collec-
tive study of elementary organisms, in which Cytology and Proto-
Morphology present to morphologists and physiologists a common
field of research.

II. In the study of the living organism, the physiologist sets
himself three main tasks : to define, to localise, and to interpret the
phenomena of life. He aims at

(a) Definition of vital phenomena : by describing them exactly,
forming, if possible, a graphic image that shall be accurate, not
merely in its outlines, but also in its minutest details.

(&) Localisation of the different vital phenomena in the several
substrata : by determining the specific energies developed by the
various elements, tissues, organs, and systems of which the body is
composed.

(c) Explanation or interpretation of vital phenomena: by in-
quiry into their genesis and inner mechanism, investigation of
the external or internal conditions on which they depend, deter-
mination of the qualitative and quantitative changes they undergo
in the play of the said conditions.

These three tasks represent three different grades of physiological
science. The first is purely descriptive; the second, descriptive

4 PHYSIOLOGY

and experimental; the third, descriptive, experimental, and
speculative. For the first, direct or indirect observation, i.e. the
exact perception of vital phenomena, suffices — whether by the
normal use of the senses only or by the help of instruments
designed to reinforce them. For the second, observation is not
enough, experiment also is required, i.e. premeditated observation,
in which the external and internal conditions of the living
phenomena can be varied. In the third, besides observation and
experiment, an energetic criticism is imperative, i.e. the logical
elaboration by the physiologist of the collected analytical data, in
order to interpret and synthetise them. This, in the majority
of cases, resolves itself into the arrangement of vital facts in
order of co-existence and succession, or of co-ordination and sub-
ordination.

In the first grade of physiological science we have an accumu-
lation of loose facts, more or less unorganised, but adapted to call
up a picture of the various and manifold energies of which the
living organism is the seat. In the second, we arrive at an
ordering and systematisation of the said energies, which enables
us more or less clearly to conceive what Galen called the " usu&
partium," i.e. the topography of the vital functions. The third
aims at harmonising the same energies, an order, by our knowledge
of the influences exerted by each element or organ upon the
other elements or organs of which the body consists, to form an
idea as to how that individual unity is built up, which is revealed
to us subjectively as the ego, objectively as the complete harmony
of functions that characterises the state of perfect health.

The first and second' grades of physiological science have a
positive, immanent value, which time can only develop and per-
fect, while the third has seldom more than a hypothetical value,
which is for the most part temporary, and therefore varies with
time. It follows that facts, if well observed, and experimental
data well harvested, are and will for ever be true in the progress
of science, while the interpretation of facts, and their logical
order, may vary greatly, and even alter fundamentally, with the
advent of new data or new discoveries.

III. In the interpretation of vital phenomena, the physiologist
seeks to apply the known laws of physics and chemistry, starting
from the obvious position that organised bodies cannot lie beyond
-the scope of the laws of Nature. The interpretation of these laws
is entirely based on the atomistic hypothesis of matter, with its
corollary that the indivisible elements of which matter is com-
posed are in themselves indestructible and invariable in their
fundamental properties, having, i.e., the same specific weight, the
same valency or saturation capacity, the same affinity. The
energy of which the atoms are the seat may be potential or
kinetic. The former is transformed into the latter, and vice versa,.

INTKODUCTION 5

either without change of the atomic groups (physical phenomena),
or with changes in the same (chemical phenomena).

These great empirical laws of the Conservation of Matter
(Lavoisier, 1789) and the Conservation of Energy (J. E. Mayer,
1842; Helmholtz, 1847) dominate living as well as non-living
Nature. A living being objectively considered may be conceived
as a machine transforming the matter and energy it derives from
the external world. As a physico-chemical science of life,
physiology will have fulfilled its task when it is able to provide
an adequate mechanical representation of the inner processes which
underlie the vital somatic phenomena, that is, when it succeeds
in giving a satisfactory explanation of these phenomena, and in
describing the processes on which they depend as links in the
causal chain of the grand Procession of Nature.

The immense value of atomic and molecular mechanics,
considered as -the basis of vital phenomena (i.e. Physiological
Materialism in the modern and scientific sense), is best appreciated
in reviewing the vast and rapid progress made by physiology,
since it has applied the positive methods of physics and chemistry
to the study of life, and has abjured the vain abstract speculations
used and abused at the beginning of the last century by the
so-called " natural philosophers."

At the same time no sincere worker in the positive or scientific
direction can deny that the specifically vital somatic phenomena,
i.e. those by which living beings are differentiated from inorganic
bodies, are inexplicable by the known laws of chemistry and
physics, and that the psychical phenomena (of sensibility and
consciousness), which for each individual constitute the culminating
point of life, are altogether remote from any mechanical explana-
tion : they cannot in any way be regarded as necessary links
in the chain of cause and effect in the natural processes of Nature.

It is probable that not a few of the still unexplained physio-
logical phenomena will become intelligible in the further progress
of physics and chemistry ; but even so, such phenomena as are
specifically vital, and psychical phenomena, will remain refractory
to any mechanical explanation.

The dynamic finality proper to living beings (which is essenti-
ally distinct from the static finality of the cognate parts of a
machine created by human industry) ; the capacity for repro-
duction, reintegration, adaptation ; the innate tendency to evolve,
to progress, to become perfect, with relative independence of
environmental conditions, — these and other specific phenomena of
living beings must, to all who are emancipated from theoretical
dogmatism, appear irreducible to a simple play of physical and
chemical energies, irreconcilable with the iron necessity of
mechanical laws. This is the position assumed by Neo-vitalisin,
which starts from this affirmation and transcends the earlier

6 PHYSIOLOGY

Vitalism, inasmuch as it recognises the experimental method as the
exclusive means of scientific progress.

When, on the other hand, we consider psychical phenomena
(sensibility and consciousness), the impossibility of reducing these
to physical and chemical processes becomes even more apparent.

Ostwald (1902) has recently attempted to formulate a unitary
conception of the world by excluding the materialistic postulates
of natural science, i.e. by eliminating the chemical concept of the
atoms and substituting the physical concept of energy, psychical
processes being regarded as special manifestations of energy. This
Energetic Monism of Osfcwald is, however, illusory. It is a new
and degenerate presentation of the old Idealistic Monism of Hegel,
in which the word energy is substituted for the empty word " idea,"
although equally devoid of definite content. In what, then, does
the essential difference between the various forms of physical and
that of the supposed psychical energy consist ? In that the former
are perceptible solely by the mediation of the senses, the latter by
introspection alone — the first being objective, the second subjective
phenomena ? It is, however, precisely in this antithesis that the
vulgar dualistic doctrine of the corporeal as distinct from the
spiritual world arises. This theory, -which was adumbrated by
primitive man from his observations of death (as appears from
ethnological and prehistoric studies), became, in the course of
centuries, deeply embedded in the mind of the whole civilised
world, resisting like a granite block the most potent and repeated
attempts of scientific and philosophical critics to dislodge it. Du
Bois-lleymond says in this connection: "It is fundamentally
impossible to explain by any mechanical means why the note
of a Konig's tuning-fork gives me pleasure, while contact with
red-hot iron gives me pain " (1872).

A more profound (but in our opinion no less illusory)
attempt to arrive at a monistic conception is that put for-
ward by Mach in his well-known Analysis of the Sensations,
and the Relations of the Physical and Psychical (3rd ed., 1902).
According to Mach the dualism between body and soul exists in
appearance only, and results from a superficial observation of
reality. More profound reflection shows that the ultimate
elements of reality are nothing but sensations. The entire
corporeal world, organic or inorganic, is for us nothing but an
aggregate of sensations ; the whole of our thought is similarly
constituted of a more or less complex combination of sensations.
Hence there is no reason to postulate an essential difference, still
less an antagonism, between the physical fact and the psychical
fact ; the one like the other, in last resort, results from homo-
geneous elements. The disparities are in appearance only, and
depend upon the different construction of the aggregates, while
the elements of these are quantitatively identical.

INTRODUCTION 7

It is obvious that if this mode of philosophising (which recalls
the mystical phenomenalism of Berkeley with his " esse est
percipi") is to give us a monistic representation free from all
hypothesis, not only the chemical concept of atoms, but also the
physical concept of energy must be given up, the psychical concept
of sensations alone being retained as the ultimate homogeneous
and irreducible element of reality. To be strictly logical, we
must cancel the entire doctrine of physics and chemistry, as based
upon mere hypothesis, and throw ourselves into the arms of pure
psychology, which alone enjoys the privilege of having for its
content the aggregates of the homogeneous elements of reality !
But how can we understand the manifold qualitative differences in
these aggregates, if once we admit them to arise from qualitatively
identical elements ? How conceive of physical facts, and what in
common parlance is called the " external world," as a complex of
sensations, if we make an abstraction of the internal world, by
means of which alone these are to arise as such in consciousness ?
How can the physiologist imagine a sensation as divorced from
the law of causality and independent of the stimulus that excites
it ? Is it not absurd to admit an essential identity between the
esse and the nosse, the esse and the posse ? How are we to
reconcile Mach's view, according to which the psychical fact is
presented as something less real than — almost (as it were) a
shadow of — the physical fact, with his general doctrine, according
to which the physical and the psychical are said to be identical
in their nature ?

If we inquire from the followers of Mach what pragmatic
value can attach to Psychical Monism (or Phenomenalism, or
Empirical Criticism, as it is termed by others) they admit that
it is nil when we are concerned with scientific work in the
various fields of research. " Here all remains as before " (writes
Max Verworn, 1905), " methods, symbols, facts, relations are all
untouched. Scientific work pursues its course unchecked." This
is equivalent to an admission that both the atomistic and the
energetic hypotheses (which constitute Materialism), and the
hypothesis of vital or psychical force (which constitutes Neo-
vitalism), must continue to function as indispensable instruments,
as poles or presumptions necessary to future discoveries and to
the progress of science in general. In order to build up science
we are constrained to descend from the rarefied regions of abstrac-
tion, and to live in the world of concrete facts, grappling with
the vital processes in their varied and complex phenomenology,
whether mechanical or psychical ; in other words, Monism must
be completed by Pluralism, according to our immediate experi-
ence.

Each new physiological experiment, each new scientific
conquest, appears as a more or less important integration of the

8 PHYSIOLOGY

science of the living ; it always signifies a process that either
tends to apply the mechanical explanation to a supposed vital
phenomenon, or brings out the essentially vital character of a
supposed physico-chemical phenomenon.

The evolutionary process of physiological science has always
been in the past, and will always be in the future, a continuous
and fruitful struggle between the two opposite tendencies of
Materialism and Vitalism. It is a mistake to suppose that either
the one or the other will ever win the final victory. Both are
one-sided ; both reflect one face only of reality. Life, in its more
highly evolved forms, results from their interpenetration and
fusion. Seen from without, it is })ody : felt from within, it is
soul : this is the great mystery that Art for ever celebrates — ra
mystery Science, with every possible and conceivable progress
in physics and chemistry, with all the experimental methods that
it may or might employ, will never be in a position to solve.

IV. As the physico-chemical science of living beings, Physiology
includes the comparative study of the vital phenomena of plants,
animals, and man.

Some vital phenomena are common to all living beings,
without distinction of species, genera, classes, or kingdoms. These
are fundamental phenomena, that is, they are the simplest and
most elementary in life. Their material substratum -is the Cell, i.e.
the simplest morphological unit, which Briicke calls the elementary
organism, whether living its independent life, or living in
association with other cells to form cell aggregates or complex
organisms.

The physiology of the cell lies at the foundation of all
physiology, because the functions of the tissues, organs, and
systems can ultimately be reduced to the vital activity of the
various cells from which they evolve. Plant physiology, as well
as animal and human physiology, derive the fundamental data
relating to elementary functions from the physiology of the cell,
and employ it as a basis in their study of the complex and special
functions of the several tissues, organs, and systems.

The science of physiology calls for a different arrange-
ment and development, and may assume a different aspect and
even content, according as it is approached from a scientific,
a philosophical, or a medical and practical standpoint. From
the first two it assumes the form and content of general and
comparative physiology, which is the necessary complement of
general and comparative morphology; both are directed to the
high aim of illustrating, tabulating, and developing the grand
doctrine of Evolution or Descent, which from Darwin onwards has
been undergoing constant transformation and integration. From
the third it assumes the form and content of human physiology,
taking Man as the goal of its investigations; it harvests the

INTRODUCTION 9

experimental data directly obtained from the higher animals ; it
utilises the data derived from pathological observations, which not
seldom have a value comparable with that of experiments on
animals ; and it dwells with special insistence on such theories as
have received or may receive an application to hygiene or preven-
tive medicine, and to clinical or curative medicine.

Such essentially practical objects are dealt with in this Text-
book, which aims at bringing the latest advances in science
within reach of all who are working at medicine and at physical
and psychological science, — and seeks at the same time to equip
the younger students, as adequately as may be, with that knowledge
of Physiology which lies at the foundation of all scientific culture
and education.

BIBLIOGRAPHY

The following list comprises only such classical Treatises on Physiology as
will be of most use to students in following the historical development of any
given physiological question : —

CLAUDIUS GALENUS. De usu partium corporis humani. Lib. xvii.

A DE HALLER. Elementa physiologiae corporis humani, 1757-66. Auctarium,

1780.
JOH. MULLER. Handbuch d. Physiologic des Menschen. 4th ed. Coblenz, 1844.

(French translation with Littre's note. Paris, 1857.)
H. MILNE-EDWARDS. Lecons sur la physiologic et 1'anatomie comparee. Paris,

1857-86.

F. A. LONGET. Traite de physiologie. Leipzig, 1879-81.
L. HERMANN. Handbuch d. Physiologie. Leipzig, 1879-81.
E. A. SCHAFER. Text-book of Physiology. Edinburgh and London, 1898-1900.
W. NAGEL. Handbuch d. Physiologie des Menschen. Brunswick (in course of

publication).
H. BEAUNIS and V. ADUCCO. Elementi di fisiologia umana, comprendenti i

principii di fisiologia comparata e di fisiologia generale. Turin (in course of

publication).

CHAPTEE I

LIVING MATTER: ITS CHEMICAL AND PHYSICAL BASIS

CONTENTS.— 1. The cell-theory. 2. Morphology of the cell. 3. Structure of
protoplasm. 4. Structure of nucleus. 5. Chemical elements of the cell. 6. Protein
basis of living matter. 7. Classification of proteins. 8. Chemical constitution of
proteins. 9. Enzymes or ferments. 10. Classification. 11. Other nitrogenous
organic substances, fats, carbohydrates or saccharides, inorganic substances.
12. Chemical structure of living matter. Bibliography.

IN Nature no phenomena can be independent of a material sub-
stratum : all are the external manifestation of the energies im-
manent in matter. Every vital phenomenon that comes under the
observation of the physiologist is intimately connected with the
living organism, and is the expression of internal causes, i.e. of the
different forms of energy inherent within that organism.

Whoever, then, approaches the threshold of Physiology in order
to study the Manifestations of Life, will feel it essential to have
some knowledge of the material substratum out of which the
living phenomena have been evolved.

I. Both in plants and animals the material substratum of vital
phenomena, the physical basis of life, consists of a substance of
highly complicated structure and constitution, soft or gelatinous
in consistency, to which Hugo Mohl (1846) gave the name of
protoplasm. In living beings this does not appear as a simple
mass, without form or boundaries ; but it is divided into minute
particles, or separate entities, known as cells. Each cell comes
from a pre-existing cell, just as every living being comes from the
ovum, which is the primitive cell. The so-called Protista, which
are the most primitive form of life (and probably constitute the
common stock whence plants and animals have developed) are
throughout their whole life represented by a single cell, which
assumes various forms and dimensions. In the Metazoa, on the
contrary, the primitive cell, or ovum, gives rise to other similar
cells, and these to other cells in turn, which are gradually differ-
entiated, transformed, and adapted to the several physiological
offices which they serve.

11

12 PHYSIOLOGY CHAP.

In the Protista each cell is a distinct and independent physio-
logical individual ; in the Metazoa each cell or cell-derivative is
still a distinct individual, but it is no longer independent, since
the life of each is more or less bound up with the life of the others
with which it is associated. The individuality of the social aggre-
gate, or that of the organism as a whole, is but an individuality
of a higher order, i.e. it is the sum of the life of each elementary
organism. This is essentially the Cell Theory, formulated by
Schleiden (1838) and Schwann (1839), reinforced and developed
by Virchow (1855), and fully confirmed by later observers.

Yet among living physiologists there are not wanting some
who believe that we must recognise a more radical difference
between the independent unicellular organisms and the cells of
which complex organisms are built up. The latter, it is said, since
they are incapable of living apart from the body of which they
form a part, do not constitute a real individual, BO that the name
of elementary organisms given them by Briicke is inappropriate.
Since the several physiological functions essential to life are very
unequally divided among the various cells of which the complex
organism consists, they must each represent a physiologically
simpler unit, and are not therefore comparable with the cells that
constitute a true individual, and which are capable ' of living
independent of other cells (E. Schenk and J. Loeb).

There is a certain amount of truth in this observation, but the
conclusions deduced from it, i.e. the negation of the cell theory,
are somewhat far-fetched. In the first place it should be noted
that incapacity to live independent of other cells cannot be predi-
cated of all the cells of which multicellular organisms are composed ;
it rises gradually with the zoological scale (cf. Chap. III. 12). It
should further be observed that the life of every organism is
invariably conditioned by its special environment, so that it perishes
when transported into other media too unlike those in which it
normally exists. In unicellular organisms the environment is
represented by the sum of the nutritive materials and the stimuli
which reach them from the external world ; in the cells of which
multicellular organisms are built up the medium is represented
by the sum of the nutritive matters and the stimuli which reach
them, either from the external world or from the other cells with
which they live in association. Lastly, in the first as in the
'second kind of cell a different grade or trend of development may
be observed for each of their vital functions.

For the rest, the cell theory, which affirms a certain functional
autonomy of the morphological elements of which the organism as
a whole consists, is founded on a synthesis of experimental facts
that can be easily verified,

(a) The survival for a certain time of parts detached from a
living organism.

LIVING MATTEK

13

(&) The non-synchronous death of the several tissues or organs
of which the organism is composed.

(c) The localisation of the effects of toxins and pathogenic
causes.

(d) The possibility of transplanting and grafting tissues and
organs.

(e) The possibility of multiplying not only plants, but also
many of the lower multicellular animals, for instance the fresh-
water Hydra by merotomy, or division into segments.

II. The organisation of a perfect cell, capable of living and
reproducing itself, requires not merely a simple lump of proto-
plasm, as was originally maintained
by M. Schultze (1863) and subse-
quently by E. Haeckel (1870), but
the interior of the protoplasmic mass
must also contain a nucleus, a con-
stituent already described by previous
observers as an essential part of
elementary organisms. The later
work of Gruber (1888) on Ehizopoda
and of Biitschli (1890) on Bacteria,
has shown that these also consist of
two characteristically differentiated
parts, corresponding to the cell proto-
plasm or cytoplasm, and the nucleus
of the perfect cell. The membrane
which envelops the protoplasm cannot
be regarded as an essential part of
the cell, because while rarely absent
in plants, it is almost always lacking
in the animal cell. The centrosome
described by van Beneden and Boveri
(1887), and considered by them to
be the third element of the cell,
appears from the more recent work of Hertwig (1891) and
Brauer (1893) to be part of the nuclear substance, which is
generally extruded into the cytoplasm during the activity of the
nucleus, to incite germination and cell division. The morpho-
logical concept of the cell is accordingly very simple : it is funda-
mentally a lump of protoplasm which includes a more or less
distinct nucleus.

The importance of the nucleus to the life of the cytoplasm can
be demonstrated experimentally, as also the importance of the
cytoplasm to the life of the nucleus.

The first experiment consists in bisecting a unicellular animal,
e.g. an Amoeba (Fig. 1), in such a way that one half contains the
nucleus and the other is deprived of it : and then observing under

FIG. 1. — Amoeba protcus. (Hertwig.) M,
nucleus ; vc, contractile vacuole ; ?,
ingesta ; en, granular endoplasm or
granuloplasm ; ec, hyaline ectoplasm
or hyaloplasm.

14

PHYSIOLOGY

CHAP.

the microscope the behaviour and final modifications of the half
provided with, and that destitute of nucleus. When the operation
is effected with as little injury as possible, the edges of the cut
soon unite again, and each half of the amoeba contracts, assuming
a globular form. After a few seconds each of these two globules
begins to move, changing its shape and creeping along, as is the
normal habit of intact amoebae. Later on, however, a difference
between the two halves is perceptible, and while the new nucleated
amoeba continues to live and grow, and behaves as a normal
individual, the half without a nucleus slackens its movements,
takes no more food, retracts its pseudopodia, and, according to the
best results obtained by Hofer, dies in ten or twelve days. This

proves the vital importance
•• ' of the nucleus.

The second experiment,
designed to show the vital
importance of the cyto-
plasm, was carried out by
Verworn on a species of
Radiolaria ; Thalassicolla
(Fig. 2). In this animal it
is possible to shell out the
nucleus, separating it from
the ray-shaped mass of the
protoplasm, and to observe
the effects of isolation.
Even when the operation
succeeds without any per-

12. — Thalassicollti nudeata. (Verworn.) From CCptlble nuclear lesion, the

without, inwards: radiating corona of pseudo - «„«!«„« inpvitnhlv

podia; gelatinous layer; layer of vacuoles; pig. nuCJCUS mevitaDly

mented sheath to central capsule ; central capsule without showing any
with nucleus. • t 6 «7

oi regeneration.

A third experiment consists in bisecting a unicellular organism,
in such a way that each half contains a portion of the nucleus and
a portion of protoplasm. This succeeds readily in a trumpet-
shaped Infusorian called Stentor, in which both protoplasm and
nucleus are elongated (Fig. 3). When bisected each half
continues to live, and regenerates gradually into a perfect Stentor,
although of smaller dimensions. This fact cannot be adduced
against the theory which considers the cell as the lowest step in
the scale of living individuality, because each half of the divided
Stentor has the value of a cell containing the two essential
constituents, nucleus and cytoplasm. It merely shows that the
living matter in the said cellular constituents may vary quanti-
tatively to a considerable extent, without forfeiting the conditions
necessary to the constitution of a complete individual.

Just as a half-cell may live and regenerate into a complete

FIG

LIVING MATTEK

15

cell, so, on the other hand, a number of cells fusing their protoplasm
into a single mass may
compose a single multi-
nuclear cellular in-
dividual (Fig. 4). Multi-
nuclear cells are fairly
common, whether as a
living species or as the
complex elements of
higher organisms. They
represent transitional
forms between the
simple niononuclear cell
and a tissue, which is
an aggregate of similar
but individually dis-
tinct cells. In some of
the lower creatures,
known as Myxomycetes,
the multinuclear proto-
plasmic mass assumes
externally the aspect of

FIG. 3. —

Stentor Roesdii. (Verworn.) 1, Complete in-
dividual, trumpet -shaped, showing in the body -axis a
very elongated nucleus of lighter appearance. When
bisected at A, each segment regenerates into a smaller,
complete individual, the upper half being represented by
2, the lower by 3.

a network which may

cover an area of several

decimetres (plasmo-

dium). This reproduces

by spores, and from each spore there develops an amoeboid cell of

distinct outlines. Eventually
the outlines of the cells dis-
appear, and they resume the
form of a reticulated plasmo-
dium (Strasburger). This
fusion of many cells into a
simple multinuclear proto-
plasmic mass is termed a
syncytium (Fig. 5).

The external form of the
cell may vary greatly both
in organisms which consist of
a single morphological ele-
ment, and in multicellular
organisms. A primary dis-
tinction must be made be-

Fio. 4.— Kvdorina degans. (Verworn.) Complex fWPPT1 ppll- nf variahlp flnrl

individual (colony) resulting from fusion of a SWeen C VRriaDlC, ana

number of flagellated individuals into a common those of fixed form. The

globular mass of gelatinous substance. , . ,

former are termed amoeboid,
because they change their shape like the Amoebae (Fig. 1), which

16

PHYSIOLOGY

CHAP.

are little naked protoplasmic bodies with no enclosing membrane,
having often a distinct nucleus. These put out in all directions
projections of their body- substance, or pseudopodia, which are
continually changing in shape. The majority of cells, however,
possess a constant form, whether the protoplasm be enclosed in

Fio. 5. — Chondrioderma di/orme, — life phases. (Stras burger.) o, dry spore ; b, turgid spore ; c, d,
dehiscence of spore-membrane and escape of cell-contents ; e,f, g, transformation of primitive-
spore into pi ri ton n and flagellate zoospore ; h, zonspore passing into state of myxamoeba ;
i, i, young myxamoebae ; k, k, adult myxamoebae ; 7, adherent myxamoebae ready to fuse ; ?n,
young plasmodium ; n, portion of adult reticulated plasmodium.

a membrane or not. Many permanent forms repeat the temporary
shapes assumed by the amoeboid cells.

The size of the cells, again, varies greatly, though they are
almost always of microscopic dimensions. The smallest Bacteria
measure only a few thousandths of a millimetre, while the largest
Amoebae exceed a tenth of a millimetre. The cells of the higher
organisms, Man included, are rarely more than eight hundredths

LIVING MATTER

17

-.-jtfTZ.

~r

of a millimetre in their largest diameter. Muscle fibres, indeed,
both plain and striated, may measure more than a decimetre, and
the nerve processes of the ganglion cells more than a metre. Still
the amount of living matter contained within a cell is always,
comparatively speaking, very small. In a bird's egg, which is a
single colossal cell, the active, living protoplasm consists only of one
very delicate layer, the whole of the rest being inactive yolk, which
is destined to feed the germ during its embryonic development.

III. Both in animal and in plant cells, protoplasm has the
same common properties : it appears as a semi-fluid, almost
always colourless substance, with no apparent morphological
structure, although it contains a variable quantity of small
punctiform gran-
ules ; it is readily
permeable by water,
which swells it up
without dissolving

it ; impenetrable as ^mc •---'•^^^^^m^m^^m^^^-n
a rule to colouring
matters during life,
it stains readily after
death. When at
rest it has an alka-
line reaction, which
may become neutral
or even acid during
activity. The hya-
line, non-granulated

protoplasm Often FK;I o. —Epithelial cell from intestine of insect larva. (Carnoy.)

forms in the Cell a mc> ce^ membrane ; pc, cell protoplasm in form of net-

" j work with granulations; mil, nuclear membrane; pn,

more Or leSS dense nuclear protoplasm with a-chromatic, reticulated substance ;

externallayer,known

as ectoplasm or hyaloplasm, to distinguish it from the internal
granular portion that surrounds the nucleus, the so-called endo-
plasm or granuloplasm (Fig. 1).

Under the high power of the microscope, this apparently
homogeneous protoplasm shows a very complicated structure.
Remak (1844) and M. Schultze (1871) affirmed that there was a
fine fibrillar structure in the protoplasm of the ganglion cells of
the nervous system, a theory subsequently extended to epithelial,
glandular, and other cells. Fromman (1865) and Heitzmann
(1873) modified this statement, and assumed a finely reticulated
structure, in which the granules would be the nodal points of the
protoplasmic network. Carnoy (1883), while admitting the theory
of a reticulum, affirmed that the granulation represented not the
network but the fluid contained in its meshes, to which he gave
the name of enchylema (Fig. 6). Finally, Butschli (1892) showed

VOL. I C

18

PHYSIOLOGY

CHAP.

that the reticulum existed in appearance only, and was merely the
optical expression of the finest vesicles in close apposition. Pro-
toplasm thus consists of a foam-like ground-substance, constructed

FKJ- 7> Alveolar structure of protoplasm. (Biitschli.) a, Delicate foam of alveolar structure

obtained by prolonged whipping of olive oil and cane-sugar; b, alveolar structure of intra-
capsular protoplasm from ThalassicoUa nudeata, as in Fig. 2.

in the form of delicate polyhedric vesicles or alveoli, closely pressed
together. The protoplasmic granules lie in greater or less num-
bers at the corners of the foam-bubbles, never in the liquid of the
alveoli themselves (Fig. 7).

Even under the low power, apparently
homogeneous prptoplasm not infrequently
exhibits drops of fluid, or vacuoles, as they
are somewhat infelicitousjy termed. Such
accidental vacuoles must be distinguished
from the permanent ones, which are so
numerous and conspicuous in certain plant
cells as to give a spongy appearance to the
protoplasm (Fig. 8). Rhythmically pulsating
vacuoles may sometimes be observed ; these
empty themselves on contracting, and refill
with fluid on dilating. This is especially the
case in certain kinds of Amoebae, and is very
y I l\ frequent among the ciliated Infusoria. In

these cases the vacuoles function as a centre
of circulation for the protoplasmic fluid.

Besides the vacuoles, there are in vege-
table protoplasm granules of chlorophyll,
FIO. s. -ceii from staminai starch, and aleuron : in animal protoplasm,
hair of Trad esc an tia fat globules, accumulations of glycogen, and

virgimca. (Strasburger.) => . ' , . ... „ => J & . '

The nucleus is surrounded granules known as " vitellm. The chloro-
1 phyll corpuscles are of capital importance

to the plant cell, since the most characteristic
part of its vital processes depends on them ; viz. the reduction of
carbonic acid, and fixation of carbon. The granules of starch,
aleuron, fat, glycogen, and vitellin are nutritive materials, products'
of protoplasmic activity, stored up within the cell.

i LIVING MATTEE . 19

Lastly, it should be noted that the unicellular animals which
have no membranes, such as amoebae, leucocytes, infusoria, and
other cells, often contain food-stuffs or other solid bodies which
they have ingested, e.g. diatoms, small algae, bacteria, etc.
(Metschnikoff), which are gradually digested, and appear as solid
inclusions in the protoplasm (see Fig. 1).

IV. Many of the peculiarities which we have noted in the
constitution or structure of the cytoplasm are characteristic of the
nucleus also. This is usually a vesicular body, surrounded by a
membrane ; at other times it may assume various forms, and may
lose the enveloping membrane which divides it from the cytoplasm.

Under a high magnification Biitschli detected an alveolar
structure similar to that of the cytoplasm, which presents the
appearance of a reticulum. The vesicles contain the nuclear fluid ;
the substance which forms them is termed a-chromatic, since it
does not stain with carmine, haematoxylin, or other dyes. Another
substance, peculiar to the nucleus, which does stain with dyes, and
is termed chromatic, can also be distinguished. This appears in
the form of small granules or filaments, threads diffused at the
nodal points of the a-chromatic substance, or collected in a heap
or kind of central skein (see Fig. 6).

V. Chemical analysis of animal and vegetable organisms has
shown that the elements which enter most constantly and
abundantly into the composition of the cell are : —

Name. Symbol. Atomic Weight.

Carbon C 12 -00

Nitrogen N 14-04

Sulphur S 32-07

Hydrogen . . H TOO

Oxygen O 16-00

Phosphorus P 31-00

Chlorine Cl 35-46

Potassium K 39-14

Sodium Na 23'04

Magnesium Mg 24-00

Calcium Ca 40-00

Iron Fe 56 '00

In addition to these twelve principal elements, other elements
occur, but in relatively smaller quantities ; they are not present
in every cell, but only in certain special plants and animals.
These are : —

Name. Symbol. Atomic Weight.

Silicon Si 28-19

Fluorine . . . . . F 18-98

Bromine . . . . Br 79 76

Iodine I 126-55

Aluminium Al 27'00

Manganese ..... Mn 53-90

Lithium ..." Li 7'00

20 , PHYSIOLOGY CHAP.

Name. Symbol. Atomic Weight.

Copper Cu 63-17

Lead Pb 206-47

Zinc Zn 64-90

With the exception of silicon, which is widely distributed in
both kingdoms, fluorine, which in small but constant quantities
enters into the chemical composition of the enamel of the teeth,
and iodine, which has lately been found in one of the constituents
of the thyroid gland, it is probable that all these elements are
without physiological significance to the ceJl-body in which they
are found, and that they enter accidentally, like many other
extraneous elements, e.g. drugs, toxins, or such as are merely
indifferent bodies.

It is worth noting that the twelve principal elements that enter
constantly into the composition of cells have all a low atomic
weight. Nine of them, in fact, belong to the first three series of
Mendelejeff s Periodic System, and only three (potassium, calcium,
iron) belong to the fourth series of the system. Further, these
are all found either in the state of elements or as very simple
inorganic combinations, which are widely diffused in the air, in
water, and in the upper layers of the soil — the only habitat of flora
and fauna.

VI. The chemical compounds of which the cell is built up may
be divided into organic and inorganic. Organic substances are
distinguished as nitrogenous and non-nitrogenous ; the former
include the Proteins and their derivatives, the latter the Fats and
Carbohydrates.

Proteins are the most important organic substances, and are
indispensable in the constitution of living protoplasm. They are
essentially distinct from carbohydrates and fats in their element-
ary composition, for in addition to carbon, hydrogen, and oxygen
they contain nitrogen and sulphur. Their molecular structure,
and the exact number of atoms of the several elements which
enter into their constitution, are still unknown to us. There is,
however, no doubt that the molecular structure of these sub-
stances is highly complex ; more so, perhaps, than that of any
other chemical substance, since the ratio of the number of the
various atoms reaches a very considerable figure.

It should be noted that the five elements above mentioned are
found in the different proteins in much the same proportions,
as appears from the following table, which gives the limits
between which the percentages of the various elements of protein
oscillate : —

C 50 — 55 mean 52 per cent.
H 9-5- 7-3 „ 7 „
N15 -17-6 „ 16 „
O 19 -24 „ 23 „
S 0-3 - 2-4 2

i LIVING MATTEE 21

These figures, of course, throw no light on the grouping of the
respective elements; i.e. the chemical structure of the protein
molecule. They show, however, that the different proteins form
a well-defined class of chemical compounds, having a strict
relation among themselves, as is further apparent from the
physico-chemical properties common to the several members, as
follows : —

(a) Non-diffusibility through the pores of animal or vegetable
membranes and of artificial parchment ; they belong, therefore, to
the class of bodies which Graham termed colloids. They are
obtained in a crystalline form with difficulty, and only by special
methods. If the colloid is fluid it is termed sol; if solid, gel.
Liquid and solid gelatin are examples of these two states.
When water is the medium in which the colloid is dispersed the
terms hydrosol and hydrogel are used respectively. Besides the
proteins, many inorganic substances can exist in a colloidal form,
e.g. colloidal metals, silicic acid, etc. There has been much recent
discussion as to the state in which the colloids exist in a solvent
(which in the case of the proteins of the living body is exclusively
represented by water). According to the latest conclusions, we
are here concerned not with true solutions — having the well-known
properties of solutions, due to the mixing of the soluble crystalloids,
salts, urea, glucose, etc., with water — but rather with very fine
emulsions or suspensions, i.e. the particles of the colloid substance
can be seen in a separate state, suspended in the liquid, and do
not enter into those intimate relations with the solvent on which
depend the physico-chemical characters of true solutions (osmotic
pressures, homogeneity under high magnification, etc.). In fact,
these colloidal solutions scarcely lower the freezing-point of the
solvent, and under the ultra-microscope a^re seen to consist of
various-sized granules moving in the body of the fluid.

(6) All proteins have, further, very definite chemical properties,
by which they are sharply differentiated from all other known
chemical aggregates, crystalloids or colloids. Their aqueous
solutions are optically active, since they deflect the plane of
polarised light to the left. Heat, the addition of small quantities
of mineral acid, salts of the heavy metals, as also absolute alcohol,
solutions of tannin, phosphotungstic acid, picric acid, etc., pre-
cipitate and often coagulate them (albumins and globulins). In
this case the protein molecule undergoes profound changes, for
after removal of the precipitating agfent the initial state of col-
loid cannot be restored ; the protein is said to be de-natured.
Proteins are further precipitated by saturation of the solvent with
salts of the alkalies or alkaline earths (sodium chloride, magnesium
sulphate, ammonium sulphate). It is important in the chemistry
of the proteins to note that in the precipitation determined by
these salts the proteins are not de-natured, or at any rate become

22 PHYSIOLOGY CHAP.

so very much more slowly — for they re-dissolve on removal of the
salts by which they were precipitated.

All proteins give specific colour reactions. The best known
are the following : —

Millon's Reaction. — On adding a solution of mercuric and
mercurous nitrate and nitrite in nitric acid (Millon's reagent) and
heating, the white precipitate first formed turns red.

Xanthoproteic Reaction. — On heating with nitric acid the
solution of protein turns yellow, and then, on the addition of
ammonia, orange.

Molisch's Reaction. — On adding a few drops of a-naphthol
and running in concentrated sulphuric acid, under the solution, a
violet ring appears at the junction of the two fluids. If alcohol,
ether, or potash be now added it turns yellow. The substitution
of thymol for a-naphthol gives a fine rose carmine, which gradu-
ally becomes green.

Biuret Reaction. — A few drops of 2 per cent copper sulphate
added to a solution of protein made alkaline with caustic potash
or soda, produces a clear violet colour in the cold. Proteoses and
peptones, which are the primary decomposition products of the
more complex proteins formed by the action of proteolytic fer-
ments (infra], give a pure pink colour, r

Sulphur Reaction. — On warming with potash and a little lead
acetate, the white precipitate which first appears (lead hydroxide)
turns brown and then black, owing to the formation of lead
sulphide.

These colour tests for proteins are important, not merely as
showing the presence of protein, but because they prove the
existence in the complex molecule of certain definite chemical
compounds to which the several reactions are due. The sulphur
test, e.g., indicates the presence of cystine which contains this
element ; Millon's test, of the tyrosine group ; the xanthoproteic
test, of aromatic groups ; Molisch's reaction, of a carbohydrate :
and so on. In fact, these chemical aggregates respectively always
give these identical reactions, which are accordingly known as
" constitutional tests." The biuret reaction is the most general
test for proteins, since it is given by all the proteins and their
most immediate derivatives (the proteoses and peptones). It is
given by biuret and other compounds which contain CO.NH
groups. It is also given by some of the less complex derivatives
(polypeptides), but not by the ultimate products of their decomposi-
tion (amino -acids).

VII. Owing to our inadequate knowledge of the exact chemical
constitution of the different proteins their classification is still
based principally upon their physical or physico-chemical
properties, e.g. solubility in water or in certain salt solutions, the
temperature at which they coagulate, etc. The Chemical and

i LIVING MATTEE 23

Physiological Societies of Great Britain adopted the following
scheme of classification in 1907 1 : —

I. Protamines, e.g. salmine, sturine.
II. Histories, e.g. thymus histone.

III. Albumins, e.g. ovalbumin, serum albumin, various vegetable albumins.
IV. Globulins, e.g. serum globulin, fibrinogen and fibrin, myosinogen and

myosin. Vegetable globulins.
V. Glutelins, e.g. wheat glutelin)

VI. Gliadins, *./ wheat gliadin /Present only in cereals.
VII. Phosplioproteins,2 e.g. caseinogen, vitellin, ichthulin.
VIII. Scleroproteins,3 e.g. collagen and gelatin, keratin, elastin, fibroin,

spongin, amyloid, albumoid, pigments.

IX. Conjugated proteins. These are combinations of protein with other
compounds.

(a) Nucleoproteins.
(6) Chromoproteins, e.g. haemoglobin.
(c) Glucoproteins.

X. Derivatives of proteins. These are formed from members of the other
groups by the action of acids and alkalies, or enzymes.

(«) Metaproteinj^f^n.

(6) Proteoses : album ose, globulose, caseose, gelatose, etc.

(c) Peptones, e.g. fibrin peptone, caseo-peptone, etc.

(d) Polypeptides, e.g. glycyl-1-tyrosine, d-alanyl-glycine, 1-leucyl-

d-glutamic acid, d-alanyl-1-leucine, etc. The majority are
synthetical compounds. Several have now been isolated
from proteins.

Albumins are coagulable proteins, soluble in distilled water, in
dilute salt solutions, in acids and bases, and they are not precipi-
tated by saturating the solutions with neutral sodium chloride or
magnesium sulphate when the solution 'is neutral, but they are
precipitated by these salts when the solution is acid. They are
precipitated by saturating the solution with ammonium sulphate.

Globulins are coagulable proteins, insoluble in distilled water
and dilute acids, soluble on the other hand in solutions of neutral
salts and dilute bases. They are precipitated on saturation with
magnesium sulphate and to a certain extent with sodium chloride ;
with ammonium sulphate they are precipitated at a lower degree
of concentration ( = J saturation) than that required to precipitate
albumin.

The vegetable globulins differ in many respects from the animal
globulins ; they have a great tendency to crystallise, and 'have
been prepared in large quantities in a crystalline form (Osborne).

Fibrinogen and myosin will be discussed in the chapters on
Blood Plasma and Muscle.

Phosphoproteins are characterised by the fact that phosphorus
enters into their composition, so that formerly they were erroneously
classed with the nucleoproteins. They are distinct from these

1 Substituted by translator for 0. Cohnheim's (1904) scheme.

2 Formerly nucleoalbumins. " 3 Formerly albuminoids.

24 PHYSIOLOGY CHAP.

inasmuch as they contain no xanthine or purine bases, which are
characteristic of nucleoproteins. They differ from nucleoproteins
also in that the phosphorus is completely removed, as inorganic
phosphoric acid, by treatment with 1 per cent caustic soda at 37° C.
for 24 hours (Plimmer and Scott). The phosphoproteins have the
properties of acids; they turn blue litmus paper red, and arp
soluble in distilled water only in the form of their alkaline salts,
from which solutions they can be precipitated by the addition of
stronger acids. Solutions of their salts do not coagulate with
heat.

Histones, on the contrary, have the character of weak bases,
their solutions being precipitated by alkalies.

The protamines form a very definite group, differentiated in
not a few particulars from the rest of the proteins : they do not
contain sulphur, and are richer in nitrogen and poorer in carbon
than the other proteins. They are distinctly basic in character,
more so than the histones. They have been isolated from the
spermatozoa of many fishes (salmine, clupine, scombrine, sturine,
etc.).

We shall deal with the derivatives of the proteins, more
particularly with the proteoses and peptones, which result from the
action of the proteoly tic ferments on Ihe more complex proteins,
in the chapter on Digestion.

The conjugated proteins are combinations of a protein with
a chemical aggregate, which is not a protein, and which Hoppe-
Seyler termed a " prosthetic group." In the nucleoproteins dis-
covered by Miescher and Bloss (1871) in cell-nuclei, this prosthetic
group is represented by nucleic acid : nucleoprotein therefore
results from a combination of protein and nucleic acid. The
nucleic acids are organic acids which contain phosphorus and
nitrogen, but no sulphur, their chemical constitution being un-
known. Their decomposition products, on the contrary, are known
to us : these are phosphoric acid, purine bases (adenine, guanine,
hypoxanthine, and xanthine), pyrimidine bases (thymine, uracil,
cytosine), pentoses (laevulinic acid).

Of the various proteins which are able to unite with the nucleic
acids to form nucleoprotein, the protamines and histones are the
principal. These enter into the molecules of the nucleoproteins of
fishes' testicles. Nucleic acid is also combined with histone in
the leucocytes of the thymus and the nucleated red corpuscles.

Nucleoproteins have distinct acid properties : they are soluble
in water and in saline solutions, still more in alkaline fluids ;
they are precipitated on the addition of acids, but are redissolved
by excess of mineral acid.

Haemoglobin (to which we shall return in discussing Blood)
results from the combination of a histone (globin) and a complex
chemical aggregate containing iron (haematin).

i LIVING MATTER 25

Glucoproteins are conjugated proteins, consisting of a carbo-
hydrate radicle combined with protein. The nature and consti-
tution of this carbohydrate group is unknown. It appears to be
a polysaccharide, since it does not reduce : it contains an ammo
group (NH2), for when boiled with acids, it usually yields gluco-
samine.

The group of proteins known as the scleroproteins includes a
series of substances which have few physical properties in common
with the preceding groups, but share many other characters with
them. They never form part of the animal cell, but compose the
skeletal or supporting substance for the cells and organs of the
body: they belong to the histological group of the connective
tissues in the widest sense of that term. There are no sclero-
proteins in the tissue fluids of animals' blood, lymph, etc. The
concept scleroprotein is essentially morphological, and from a
chemical point of view includes most various bodies.

As proteins, the scleroproteins have many properties in common
with the other groups. By the action of acids or of proteolytic
ferments they are split into proteoses, peptones, and amino-acids ;
they form salts ; and they have the same percentage composition
and give the same colour reactions.

Of the various scleroproteins enumerated in the table, we may
say that collagen is the general substance of bone, cartilage, and
connective fibres ; on boiling, it takes up water and is transformed
into gelatin. Keratin, the ground substance of the cornea, is an
elaboration product of the epidermic cells of the cutis. Elastin, a
component of the fibres of elastic tissue and the ligamentum
nuchae, is a product of connective tissue cells. Fibroin, the
principal component of silk, is an elaboration product of the
spinning gland of the silkworm. Spongin is the organic support-
ing substance of the bath sponge. Conchiolin is the organic matrix
of the snail and other molluscs. Amyloid, lastly, is a substance
which is absent in the healthy organism, but accumulates in
enormous quantities under the influence of various pathological
degenerative processes.

Albumoid is the name which has been given to many different
substances found in various organisms, e.g. the membrana propria
of certain glands, the vitreous membrane, sarcolernma, the solid
constituents of the lens, scales of fishes, etc. These are also
scleroproteins.

Lastly, the group of pigments, or melanin s, includes all those
various pigments, brown, black, chestnut, etc., which determine
the characteristic hue of hair, fur, and choroid, and which are found
in the so-called melanotic tumours.

VIII. The analytical and experimental work on the chemical
structure and constitution of proteins, as recently carried out by
such distinguished physiological chemists as Kossel, Hofmeister,

26 PHYSIOLOGY CHAP.

and more particularly Fischer and his school, has led within the
last few years to important results. While these do not as yet
account fully for all the different chemical units which build
up the complex protein molecule, they represent a great advance
in this direction. A brief review of this work, which has
profoundly modified most of the theories previously held by
physiologists, is essential.

The analytical method is invariably employed in investigating
the chemical structure of highly complex bodies. The complex
substance must be decomposed and split up into its simpler
constituents, i.e. into the units of which it is built up. For
proteins, hydrolytic cleavage is the method of artificial decom-
position that gives the best results, i.e. decomposition with
absorption of molecules of water. This hydrolytic cleavage or
hydrolysis of proteins may take place by the prolonged action—

(a) Of mineral acids, by boiling the protein with concentrated
hydrochloric acid or 25 per cent sulphuric acid for twelve to fifteen
hours (method proposed by Fischer, and generally used in his
laboratory) ;

(6) Of alkalies ; and
(c) Of proteoly tic ferments.

The most important result of all the researches in to1 hydrolytic
cleavage up to the present time is that even the most unlike
proteins have, among themselves, a very similar constitution,
judging from the end products. These are invariably the same,
no matter what process of hydrolytic decomposition is employed.
It was formerly believed that one essential difference only existed
between hydrolysis by the proteoly tic ferments and that by acids
and alkalies': the disintegrating action of the ferments was
supposed to be more gradual, since before reaching the final
products of cleavage, which no longer yield the biuret reaction,
those intermediate cleavage products were obtained which are
known by the name of proteoses and peptones (of which we shall
treat fully in the physiology of Digestion). These products were
supposed not to appear in the cleavage effected by strong acids
and bases, but complex products with similar properties have now
been isolated and studied by Fischer and Abderhalden. Some of
the final products of cleavage are still unknown ; most of them,
however, have been isolated and identified. They are the organic
' compounds known as amino-acids, or organic acids, in the molecule
of which an amino-group (NH2) is substituted for one or more
atoms of hydrogen ; our knowledge of the various amino-acids that
arise from proteins by cleavage is mainly due to Fischer, who has
devised new methods for their isolation and recognition. The
number and variety of the amino-acids at present isolated is shown
in the following table of Abderhalden : —

i LIVING MATTER 27

I. Aliphatic or Fatty Series.

1. Mono-aniino-mono-carboxylic acids : glycine

alanine
valine
leucine
isoleucine.

2. Mono-amino-oxy-mono-carboxylic acids : serine.

3. Mono-amino-tliio-mono-carboxylic acids : cysteine and cystine.

4. Mono-amino-di-carboxylic acids : aspartic acid

glutamic acid.

5. Di-amino-moiio-carboxylic acids : lysine

arginine.

6. Di-amino-oxy-mono-carboxylic acids : di-arnino-tri-oxy-dodecanic acid.

II. Aromatic Series.

1. Mono-amino-mono-carboxylic acids : phenylalanine.

2. Mono-amino-oxy-mono-carboxylic acids : tyrosine.

III. Heterocyclic Compounds.

1. Mono-amino-mono-carboxylic acids: proliiie (a-pyrrolidine-carboxylic acid)

tryptophane (indole - a - ammo - pro-

pionic acid)
liistidine (imidazole - a - ammo - pro-

pionic acid).

2. Mono-amino-oxy-mono-carboxylic acids : oxy -proliiie (oxy-pyrrolidine-

carboxylic acid).

Some chemists further regard the carbohydrate (glucosamine)
group as a cleavage product of proteins : this group, however,
occupies a special position, inasmuch as it is absent in many
proteins, while in others its presence is doubtful, and, moreover,
those which contain large amounts of it 'are by many considered
to be compound proteins (gluco-proteins). We may suppose that
as all proteins contain units which exhibit great affinity to the
molecule of a carbohydrate, since they contain six carbon atoms,
there is a possible transition from this group to the carbohydrate
molecule. Lysine, e.g., which is an amino-acid invariably present
among the cleavage products of all proteins, has a formula very
like that of glucosamine and glucose, as will be seen from the
following table : —

CH2(OH) CH2(OH) CH2(NH2)

CH(OH) CH(OH) CH2

CH(OH) CH(OH) CH2

CH(OH) CH(OH) CH,

( ' 1

CH(OH) CH(NH2) CH(NH2)

CH : 0 COOH

CH: 0

Glucose Glucosamine Lysine

28 PHYSIOLOGY CHAP.

Keturning to the various amino- acids which represent the
products of the hydroly tic cleavage of proteins, we must note the
important fact that, with the exception of the protamines, all
proteins hitherto decomposed contain the] same units. One or
other of the amino-acids, e.g. glycine in egg albumin and serum
albumin, may be wanting, but these are rare exceptions.

What differentiates the several proteins among themselves is,
on the other hand, the varying quantitative relations of the differ-
ent amino-acids which compose the protein molecule. In some
proteins, certain special amino-acids, e.g. leucine and more particu-
larly glutamic acid, occur in enormous quantities, as in the
proteins of plant seeds. There are great differences, again, in the
relative proportions of the mono- and di-amino acids ; the latter
are found in large quantities in the protamines, while they are
almost absent in some of the scleroproteins.

The histones occupy an intermediate position between the pro-
tamines and the coagulable proteins (albumins and globulins).

From these facts it may be anticipated that we shall before long
be able to classify the various groups of proteins on the basis of
similar end products. Indeed, from the fact that the same units
enter into their constitution, although in different proportions for
the different substances, we can even" now to a certain extent
perceive how the several alimentary proteins may be converted
into the other definite proteins of the animal body.

It has been objected that the ultimate cleavage products of
the artificial hydrolysis of proteins are not really pre-formed as
so many units in the protein molecule : but the various data
recently acquired meet this objection. The following may be
briefly noted :—

(a) In whatever way the hydrolytic cleavage of any protein is
effected, whether by acids, by alkalies, or by proteolytic ferments,
the final products are approximately the same in quality and
quantity. Tryptophane is the sole exception, since it is largely
destroyed on hydrolysis by acids.

(b) Fischer has succeeded in artificially combining two or
more molecules of amino-acid, and has thus obtained synthetically
the chemical compounds which he terms polypeptides, which in a
number of properties have affinity with the natural proteins. The
type on which this synthesis has been successfully carried out is
represented by the simplest dipeptide, which is known as glycyl-
glycine, and which results from the coupling together of two
molecules of glycine (or glycocoll) according to the following
equation : —

NH2.CH2.COOH + HNH.CH2.COOH =

glycine glycine

NH2.CH2.CO.NH.CH2.COOH + H20. ;

glycyl-glycine

i LIVING MATTEE 29-

Here the basic group (NH2) of one molecule of glycine is
united with the acid group (COOH) of the second, with loss of a
molecule of water — a true polymerisation. It is clear that by the
same process another molecule of glycine may be united with this-
compound (dipeptide), thus making a tripeptide, and so on. If
we remember that all other amino-acids are capable like glycine
of similar combination between themselves and with the molecules
of other amino-acids, it is evidently possible to obtain a very
numerous series of different and more or less highly complex
compounds.

Fischer and his school have already succeeded in producing
synthetically some seventy similar compounds ; the most complex
is an octadecapeptide, which consists of eighteen molecules of
amino-acid united together in this manner.

It is important to note that many of these polypeptides,
particularly the more complex, give the biuret reaction, which, as-
we have said, is the most characteristic test of protein, and that
some of them are digested by pancreatic juice, which disintegrates-
them into the amino-acid components, as is the case with natural
proteins.

IX. Enzymes and ferments must further be included in the-
protein group, and belong in all probability to the nucleoproteins,
or, according to others, the scleroproteins. These, being elabora-
tion products of the living cell, represent, according to the latest
view (Hofmeister, 1901), the chemical instruments by means of
which all chemical changes of the different substances which
form the material substratum of living matter take place. These
chemical changes result in the disintegration of the complex
molecule into simpler compounds (cleavage by analytical ferments),,
either by rendering it suitable in form and quality for assimilation,
as in the case of the various digestive ferments of the alimentary
canal in animals, or by setting free the potential energy which is
manifested in the form of heat or movement. To this large class
of analytic ferments another class of ferments is opposed, whose
work consists not in the chemical cleavage of substances with
large molecules, but in synthetic processes, in which simple
molecules unite to form more complex molecules, as occurs in the
so-called anabolic phase of metabolism in living organisms. The
theoretical existence of these supposed synthetic ferments has so
far not received any decisive proof. We will therefore content
ourselves with a rapid survey of the class of analytic ferments, of
which much has been learnt by recent work.

The fermentative processes of decomposition were, until recently,,
divided into two great classes which were very distinct from one
another. In the one class were placed all the non-organised
ferments or enzymes, which were regarded as the elaboration pro-
ducts of the various secreting glands, capable of being isolated,,

30 PHYSIOLOGY CHAP.

and of acting as pure chemical agents, independent of the living
elements which produced them. The several digestive enzymes
of the gastro - intestinal tract in animals were considered as
examples of these non-organised ferments.

The second class comprised the so-called organised ferments, or
ferments proper, represented by micro-organisms (fungi, bacteria,
etc.), the action of which was then held to be in direct dependence*
upon the vitality of the latter, and to cease on their death or
disorganisation. Saccharomyces cerevisiae, which determines the
alcoholic fermentation of glucose (Pasteur), was regarded as the
prototype of such organised ferments.

Now, however, in consequence of Buchner's work (1899), this
distinction can no longer be maintained. Buchner has demon-
strated experimentally that it is possible to extract from the cells
of beer-yeast, when exposed to enormous pressure, a substance rich
in protein, which is free from Jiving elements, and is able to set
up the alcoholic fermentation of solutions of glucose. The
property by which yeast cells ferment glucose is therefore due,
not to a true vital process, but to the action of an enzyme or
zymase, produced by the cell. Specific enzymes of other micro-
organisms formerly held to be organised ferments (the bacilli of
lactic fermentation, of acetic fermentation, etc.) have .also been
isolated.

All enzymes are now regarded as organic substances (most
probably of the nature of proteins) which are elaboration products
of the living cells, from which they can be separated and extracted
by various methods without losing their activity. Generally
speaking they can be extracted from the cells and the tissues, on
treating these with water or glycerin. The latter solvent, in
particular, yields solutions that remain active for a considerable
time, and has been largely employed in practice to extract these
•enzymes.

It should be stated that the enzymes are frequently not found
pre-formed within the cells which produce them, but are as it were
in a potential state. The complete development of their specific
enzyme activity necessitates the further action of oxygen and
other chemical compounds known as kinases. The mother-
substances from which the enzymes are derived are called
zymogens or pro-enzymes. We shall discuss these at length in
'speaking of the digestive ferments, since there is in the intestine
a substance which activates the pancreatic enzymes (enter o-kinase).

No characteristic chemical reactions are common to all enzymes;
generally speaking, they are precipitated from their colloidal
solutions by alcohol, and are destroyed by high temperatures from
+ 80° to + 100° C. In order to recognise them, it is necessary
to observe the properties which characterise their mode of
action. In the first place enzymes, in consequence of their

i LIVING MATTEE 31

peculiar chemical action, do not form stable combinations with
the substances on which they act, or with the decomposition
products arising from their activity. An infinitesimal quantity of
enzyme is able to act upon a relatively enormous quantity of
fermentable substance. It has been found, e.g., that one part of
invertase is capable of splitting up 100,000 parts of saccharose,
and one part of chymosin or rennet of coagulating 400,000 parts
of caseinogen.

A second property of enzymes is the specific character of their
action, inasmuch as any one enzyme acts only upon a definite
substance, or upon a restricted group of allied substances. Enzyme
action is always in strict relation with the configuration and con-
stitution of the atomic grouping of the relative molecules, to
which the enzyme is as rigorously adapted as the key to the wards
of a lock — to repeat once more the picturesque expression of E.
Fischer. This specific action is, in fact, so conspicuous as to serve
as a method of distinguishing isomeric chemical compounds from
one another.

Enzyme action is further influenced by various external
conditions, e.g. the reaction of the liquid : some ferments are
active only in an acid medium, others — and far the greater number
— in a neutral or faintly alkaline medium.

Temperature has a marked influence on the course of enzyme
activity, which usually increases with the rise of temperature
to a certain point representing the optimum, after which a
further rise of temperature diminishes the enzyme action until
it disappears.

The accumulation of cleavage products has a marked inhibitory
influence on the development of enzyme activity ; the inhibition
ceases so soon as these products are removed.

How is it possible to explain the action of enzymes ?

Certain inorganic substances exhibit properties highly similar
to those of the analytical enzymes we have been considering, since
they are capable of producing cleavage processes which do not
essentially differ from processes of fermentation. These sub-
stances, which have been known for some time to chemists, are
the so-called catalysers, and determine the process of catalysis
(Ostwald). A classical example of catalytic action is that repre-
sented by the decomposition of hydrogen peroxide (H202) into
oxygen (0) and water (H2O) by platinum black. A trace of this
substance will decompose an enormous amount of hydrogen
peroxide without any loss of activity.

Bredig (1899) has recently enlarged the class of catalysers by
showing that all metals in a colloidal state, to which he gives the
name of inorganic ferments, belong to it. Moreover, he has
brought out so many interesting coincidences between the action
of these catalysers and that of enzymes as to render the hypothesis

32 PHYSIOLOGY CHAP.

highly probable that both classes of substances act in virtue of the
same principle.

To Ostwald is due the special distinction of having effectively
contributed to our knowledge of the mode of action of catalysers.
According to him, every catalytic process consists essentially of a
change of velocity in a chemical process, which occurs spontaneously.
" A catalyser is a body which, without appearing in the end product
of a chemical reaction, alters its velocity by accelerating or by
retarding it."

This theory is especially applicable to the example cited of
hydrogen peroxide and platinum black : we know, in fact, that
the hydrogen peroxide slowly decomposes by itself into water and
oxygen, to such an extent that after a few days there is no longer
any trace of the hydrogen peroxide in an open vessel containing
it. The platinum black merely accelerates the spontaneous
process of scission. The same thing must occur in the case of
enzymes and the substances which they split up.

This is not the place for discussion of the various theories
put forward to explain the action of catalysers and of fer-
ments : it need only be said that nowadays everything points to
the conclusion that this action is effected not directly, but by
the formation of intermediate products (which do no.t, however,
appear in the end products of cleavage), and that according to
Euler enzymes and catalysers act as collectors of ions.

X. In the present state of physiology the only possible basis
for a classification of the different enzymes is the changes which
they effect.

According to Hainmarsten, the enzymes which have more
especially been made the subject of experimental research may be
subdivided into two great classes, i.e. liydrolytic and oxidative.

The class of hydrolytic ferments, i.e. those which split up
complex chemical aggregates into simpler molecules by the
absorption of molecules of water, comprises all the several digestive
ferments, which, as we shall see, fulfil the office of disintegrating
complex proteins, polysaccharides and alimentary fats into simpler
compounds. The latter are better adapted for absorption by the
intestinal epithelium, where they are either finally split up, or
elaborated into new and more complex chemical compounds by the
metabolic activity of the tissues. They are :—

(a) PrQteolytic or proteoclastic enzymes, which split up
proteins, and of which we have already spoken. In the animal
body there are two (according to some authors, three) different
types of proteolytic ferments — pepsin, trypsin, and to these,
according to some modern workers (O. Cohnheim), erepsin must be
added. We shall deal fully with these enzymes in the chapter on
Digestion. Vegetable proteolytic ferments (e.g. papain) are also*
known.

i LIVING MATTEE 33

(6) Amy-olytic enzymes or amylases, which split the poly-
saccharides (starch, etc.) into di- or mono-saccharides. To these
belong the various diastases of the animal and plant kingdom
(ptyalin, aniylopsin). The so-called invertases which split di-
saccharides into mono-saccharides are in close relation with these ;
e.g. maltase which splits maltose into two molecules of glucose ;
invertase, which splits saccharose into one molecule of fructose and
one of glucose ; lactase, which splits lactose into one molecule of
glucose and one of galactose.

(c) Lipolytic enzymes or Upases, which split neutral fats into
their components, i.e. glycerin and fatty acids. To these belongs
the so-called steapsin of the pancreatic juice to which, according
to -the latest investigations, must be added another lipase, formed
by the gastric mucosa.

The class of hydrolytic ferments further includes a number of
other ferments recently discovered in the tissues and organs of
animals and plants, such as arginase, which splits arginine into
urea and ornithine ; adenase and guanase, which split up adenine-
and guanine respectively into ammonia and hypoxanthine or
xanthine ; urease, which splits urea into ammonia, water, carbonic
acid, etc.

A special position (which has been little noticed) is occupied
by the so-called coagulating enzymes, such as the rennin or
chyrnosin of the digestive tube, which forms casein from the
caseinogen of milk, and thrombin or thrombase, which determines
the clotting of blood by transforming fibrinogen into fibrin, as we
shall see in treating of blood plasma.

The class of oxidising ferments contains all those ferments
which determine the disintegration of complex substances by
oxidising them, by a process highly similar to that which occurs in
inorganic nature in the various forms of combustion, e.g. of carbon,
which burns, combining with the oxygen of the air.

These ferments, too, are analytic, i.e. they break down the
complex chemical compounds into simpler compounds, making
them richer in oxygen derived from the atmosphere or other
sources — and thereby liberating a certain quantity of potential
chemical energy. Great importance is ascribed to these oxidising
ferments, as they are the agents of the various processes of oxida-
tion, which occur, as we shall frequently find, within the living
organism : and it has been possible, by modern methods of research,
to isolate a large number of enzymes belonging to this class from
animal and vegetable tissues.

Direct oxidases (the name given to the oxidising ferments)
must be distinguished from the indirect, which are known as-
peroxidases. The former are capable of causing oxygen to
act directly; the latter can only oxidise in the presence of
peroxides (hydrogen peroxide). Oxidases give a blue reaction
VOL. i D

34 PHYSIOLOGY CHAP.

directly with tincture of guaiacum, peroxidases only in presence
of a peroxide.

Some consider as a third group of the oxidising ferments the
so-called catalases, which split up hydrogen peroxide into oxygen
and water, but never give a blue reaction with tincture of
guaiacum.

The alcoholic fermentation of glucose by means of beer yeast,
or the ferment known as zymase, which was first isolated by
Buchner from the cells of that micro-organism, is not a true and
proper oxidation in which free oxygen is absorbed by the sugar —
as may be deduced from the fact that such fermentation takes
place anaerobically, and according to the equation : —

C0H12O6 = 2C,H5OH + 200.,
Glucose Alcohol Carbonic
acid

It should rather be considered as an internal or intra-niolecular
oxidation, by which part of the molecule of glucose is oxidised,
and burns at the expense of the other part, till it finally splits up
into alcohol and carbonic acid. According to recent investigation,
we have here the co-operation of two separate and distinct
enzymes, one of which, lactolase, or lactacidase, converts sugar into
lactic acid, while the other, zymase, or alcoholase, splits the lactic
acid into alcohol and carbonic acid.

According to some authors (whose conclusions have, however,
been warmly disputed), a similar anaerobic fermentative process of
glycolysis takes place in animal tissues.

In conclusion we must mention another class of ferments, of
which we know at present even less than those already discussed
— the so-called reducing ferments, reductases or hydrogenases.

Another classification of enzymes is based upon the difference
of place in which they normally occur. Thus, to the ferments
known as extracellular or secretory, because normally found in the
liquids secreted by the various glands or cells, are opposed the
intracellular ferments or endo-enzymes, which are found within
the cell, and represent the chemical agents by which the cells are
able to split up or fabricate the several chemical components of
their substance. To this class of endo-enzymes belong Buchner's
zymase, many of the oxidases, and also a series of hydrolytic,
proteoclastic enzymes, which according to Vernon are of the type
of O. Cohnheim's erepsin.

To these intracellular proteolytic ferments are due the
phenomena of post-mortem autodigestion or autolysis, described
for the first time by Salkowski (1900), which occurs in the organs
or organic fluids, when isolated from the body, and kept free of
bacterial or extraneous enzymatic contamination. After a certain
lapse of time it can be shown that protein cleavage has taken

i LIVING MATTER 35

place in the tissues or fluids, accompanied by a similar cleavage of
fats and carbohydrates.

The phenomena of post-mortem autolysis have been the subject
of numerous recent researches, in the hope of throwing some light
upon intra vitam, intracellular, fermentative processes, which
we must assume to be of great importance in the metabolism of
the tissues and of the living cells. The results so far obtained
are not, however, decisive enough to serve as the basis of any
definite conclusion.

XL The proteins of living matter are always accompanied by
a large amount of simpler substances, nitrogenous or non-
nitrogenous, which represent products of decomposition or of
retrogressive changes in these substances, or in nutrient substances
from outside, which have been more or less elaborated by the
activity of the cell. The name deutoplasm has been given to
these substances as a whole, that of cytoplasm being reserved for
the living substance generically known as protoplasm.

The nitrogenous products of the retrogressive metamorphoses
of protein form a series of well-defined chemical substances, many
of which are eliminated with the urine in very varying amounts
in the higher animals. The largest in quantity and in nitrogen
content is urea, next come uric acid, hippuric acid, creatine and
creatinine. The purine bases form a distinct group already referred
to, xanthine, hypoxanthine or sarkine, adenine, guanine, and they
are the decomposition products of nuclein. These substances
cannot all be extracted from the tissues, owing to the minimal
quantity in which they are present. Another group of nitrogenous
and phosphorised substances, the lecithins, occur, according to
Hoppe-Seyler, in every plant and animal cell, and in particularly
large quantities in the elements of nerve, the blood corpuscles and
in yolk of egg. In its chemical characters (solubility in ether and
alcohol, insolubility in water) lecithin shows great similarity to
fats. It resembles nuclein inasmuch as it contains phosphorus,
and is capable of forming unstable combinations with albumin and
other substances. The yolk of egg contains a combination of
lecithin with vitellin. Protagon, extracted by Liebreich (1865) from
the brain, is the combination of a lecithin with cerebrin, a nitrogen-
ous substance free from phosphorus, similar to the glucosides.

The non-nitrogenous organic products which enter into the
chemical constitution of the cell are represented by the fats and
carbohydrates. These originate partly in the consumption of
proteins, partly from external food-stuffs, or their transformations
as effected by the cell-enzymes.

Chemically considered, the fats represent combinations of
glycerin (triatomic alcohol) with the acids of the fatty series
(stearic, palmitic, butyric, valerianic, caproic), as also with oleic
acid, which does not belong to the normal fatty series.

36 PHYSIOLOGY CHAP.

Cholesterin resembles the fats in certain of its characteristics,
though absolutely unlike them in its chemical constitution ; it is
regularly found in every animal and plant cell, particularly in the
brain and liver. Since it is a secretion from the skin of man and
other animals, it is found in the epidermal structures (hair, fur,
feathers, nails, etc.), for which it forms a kind of protective grease.
Cholesterin is a monatomic alcohol of unknown constitution, which
crystallises from alcoholic solution in laminae like mother-of-pearl.
Like glycerin, it forms with fatty acids compounds which corre-
spond to the fats.

From a chemical point of view the carbohydrates are aldehydic
or ketonic derivatives of polyhydric alcohols. They may be divided
into three groups: (a) monosaccharides, (V) di-saccharides, (c) poly-
saccharides.

(a) Among the monosaccharides are more particularly grape
sugar (glucose or dextrose) and fruit sugar (fructose or laevulose),
which are abundant in plant juices; the first also occurs in animal
tissues. They turn the plane of polarised light to the right or
left. They are readily oxidised ; they are fermented by yeast, and
converted into alcohol and carbonic acid : —

C6H1206=2C2H5QH + 2CO,,.

They have the property of readily abstracting oxygen from the
surrounding medium, and behave as reducing agents to oxidised
compounds. This property is utilised in detecting the presence of
sugars, and also in estimating them. The tests most used are
Trommer's and Bottger's. In the former the sugar solution,
rendered alkaline with caustic potash or soda, on adding a few drops
of dilute copper sulphate, and heating, reduces the copper oxide
to cuprous oxide, a suboxide which forms a reddish-yellow pre-
cipitate. In the second test a few drops of bismuth subnitrate
are added to the alkaline solution of sugar, which is turned black
by the reduction of the bismuth salt to the metallic state.

Besides these two tests, which, since they are based on the
reducing property of glucose, are not, strictly speaking, specific to
this compound, but are common to all the reducing substances,
three other specific tests are known for glucose, namely Moore's
test, the phenyl-hydrazine test, and that of alcoholic fermentation
(biological test).

In the first the solution of glucose is warmed, after diluting it
with about a quarter of its volume of caustic soda or potash. The
mixture first turns yellow, and then successively (according to the
content of sugar) orange, brown, dark brown, giving off the char-
acteristic odour of burnt sugar or caramel, which becomes more
intense on acidification.

The second test consists in warming the glucose solution with

i LIVING MATTER 37

acetate of phenyl-hydrazine ; characteristic yellow crystals (needles)
of phenyl-glucosazone are formed (E. Fischer).

The biological test is based on the fact that beer yeast is able
to provoke alcoholic fermentation in a solution of glucose.

We shall give the quantitative tests for glucose in dealing
with urine.

(6) Di-saccharides have the formula C12H22OU, which represents
the combination of two molecules of a monosaccharide with
elimination of a molecule of water. The most important are cane
sugar (saccharose) arid milk sugar (lactose). On warming with
dilute mineral acids, and under the action of certain bacteria, the
di-saccharides are inverted, i.e. transformed into monosaccharides.
Under the fermentative action of the Bacterium lacticum these last
are transformed into lactic acid (C6H1206 = 2C3H603). With
Bacillus butyricus lactic acid undergoes further decomposition,
giving rise to butyric acid, carbonic acid, and hydrogen :—

2C3H003 = C4H802 + 2C02 + 4H.

(c) Poly sacchar ides are also anhydrides of monosaccharides,
and result from the combination of several molecules ; they there-
fore have a high molecular weight, which differs in different
compounds of the group. Their general formula is wC6H1005.
They do not taste sweet, are generally amorphous, are partly
soluble, partly insoluble in water, and are convertible into
monosaccharides by various means. They include a series of
bodies widely distributed in both plant and animal cells. The
most important are starch, which in the form of stratified
corpuscles is found in the protoplasm of many plant cells ; glycogen
or animal starch, which occurs in almost all animal tissues, but
particularly in the amorphous granules of the hepatic cells, as also
in muscle fibre, embryonic tissue, and proliferating cells in general ;
animal and vegetable gums; cellulose, which is the principal
component of the cellular membranes of plants, and is also found
in the animal kingdom in the mantle of Tunicata and the
chitinous skeleton of insects.

Polysaccharides behave variously to solutions of iodine. The
starches turn blue, glycogen brown ; cellulose does not stain at all
with iodine, and only assumes a bluish tint on treatment with
sulphuric acid.

In addition to free carbohydrates, living protoplasm contains
other compounds such as mucin and chitin, as is shown in their
derivatives and decomposition products (dextrin, sugar, lactic acid,
butyric acid, etc.).

The inorganic substance of elementary organisms consists of
water, salts, and gases.

Water is indispensable to the activity of living matter, since

38 PHYSIOLOGY CHAP.

it dissolves the single particles, and renders them capable of being
transported. It is present partly in chemical combination, partly
as solvent for the various substances of the cell-contents. The
amount by weight of water in the tissues is on an average over
50 per cent. According to von Bezold, the total content of water
in the human body is about 59 per cent. Bone contains 22 per
cent water, liver 69 per cent, muscle 75 per cent, the kidneys 82
per cent.

The water holds in solution a number of salts, which are never
wanting in living substance. Chlorides largely predominate ; next
come the carbonates, sulphates, phosphates of the alkalies and
alkaline earths. Such are the chlorides of sodium, potassium, and
ammonium ; the carbonates, sulphates, and phosphates of sodium,
potassium, calcium, magnesium, and ammonium. A considerable
part of these salts is probably in chemical combination with the
organic substances.

The gases, oxygen, carbonic acid, and nitrogen, when not
chemically combined, are simply dissolved in the water ; very
occasionally they occur in the form of gaseous vesicles, as in
certain unicellular Ehizopods.

XII. After this bird's-eye review of the vast province of the
chemistry of elementary organisms, undertaken solely with the
object of classifying into groups and subgroups the several bodies
that compose the substratum of the phenomena of life, it must
again be emphasised that we are far from any adequate knowledge
of the chemical structure of living matter. It is impossible to
investigate this living matter without first killing it, i.e. destroying
its vitality. The chemical compounds, organic and inorganic,
which we have seen to exist in plants and animals, are only the
products of this destruction, i.e. they represent the chemical
aggregates, which can be recognised and isolated from the dead
body. They certainly exist in the cell ; but we are entirely
ignorant of the mode in which they are associated and combined
among themselves, so as to compose the living matter. Nor
should this surprise us, when we reflect that with the ordinary
methods of chemical analysis we have no means of ascertaining
the exact chemical nature of the individual salts contained, e.g. in
a mineral water. We can only determine the quality and quantity
of the acids and bases contained in it ; as to what these salts are,
and how they are mixed together, we know nothing. Any state-
ments in regard to this are mere guesswork.

The physiologist needs to be very circumspect and cautious in
applying the data thus derived from the chemistry of dead matter
to the phenomena of living substance, in which the chemical
relations of the several molecular aggregates are very different, and
the molecules themselves are highly complex and excessively
unstable.

i LIVING MATTER 39

Immense progress has been made of late years in the know-
ledge of the finer morphological structure of the cell, which
must help in determining the chemical differences between the
protoplasm and the nucleus, respectively. The first advances in
this direction are due to the methods of Micro-Chemistry.

Kossel's work (1891) has shown that in the nucleus, compounds
of protein with substances containing phosphorus largely pre-
dominate, while the cytoplasm consists principally of simple
proteins and their compounds with combinations which contain
no phosphorus. Miescher had previously demonstrated (1874)
that the nucleins which he discovered resist the digestive action of
gastric juice, and that on placing cells of various kinds in this
juice the cytoplasm of the cell dissolves, while the nuclei remain,
although of smaller size. Malfatti (1892) next showed that it is
the chromatic substance and the nucleolus of the nuclei which do not
digest, while the nuclear fluid and a-chromatic substance dissolve.
This proves the chromatic substance and the nucleolus of the nuclei
to consist essentially of nucleins or their combinations, while the
cell protoplasm consists of other proteins. Lastly, Lilienfeld and
Monti (1892) showed that ammonium molybdate is a micro-
chemical reagent for phosphorus -containing substances, in the
presence of which phospho-molybdic acid is formed, which stains
brown on the addition of pyrogallol. By means of this reagent
it has been ascertained that the compounds of phosphorus, in the
most dissimilar cells, are almost exclusively contained in the
nucleus.1

Carbohydrates and fats, on the other hand, are almost ex-
clusively localised in the cytoplasm and limiting cell membrane.

Nothing is known in regard to the localisation of the inorganic
compounds; except that, according to Yahlen, potassium compounds
are absent from the nuclei of cells.

BIBLIOGRAPHY

F. HOPPE-SEYLER. Pliysiologische Chenrie, I. Teil, Allg. Biol. Berlin, 1877.

0. HERTWIG. Die Zelle u. die Gewebe. Jena, 1893-1898. (English translation,
The Cell, Campbell, 1895.)

M. VERWORN. Allgeraeine Physiologic. 4th ed. Jena, 1906. (English transla-
tion, General Physiology, by F. S. Lee. Macmillan, 1899.)

R. NEUMEISTER. Lehrbuch d. physiologischen Cheniie. Jena, 2nd ed., 1892.

F. BOTTAZZI. Trattato di chimica fisiologica. Milan, 1898.

0. HAMMARSTEN. Lehrbuch d. physiologischen Cheniie. Wiesbaden, 6th ed.,
1907.

E. ABDERHALDEN. Lehrbuch d. physiologischen Chemie. Berlin and Vienna,
1906.

E. FISCHER. Untersuchungen iiber Aniino-sauren, Polypeptide, u. Proteine.
Berlin, 1896.

1 Scott has shown that it is only the inorganic phosphates which react with
this reagent. Organic phosphorus compounds do not react, especially those of the
nuclein type, which are not readily hydrolysed into phosphoric acid.— PLIMMER arid
SCOTT.

40 PHYSIOLOGY CHAP.

C. OPPENHEIMER. Die Fermente u. ihre Wirkungen. Leipzig, Vogel, 1903.

O. BIIEDIG. Die Elemeute d. chemischen Kinetik, mit besonderer Beriick-

sichtigung des Katalyse u. der Ferment- Wirkung. Ergebnisse d. Physiol., I.

Part I., 1901.

Recent English literature of the subject : —

F. G. HOPKINS and S. W. COLE. A Contribution to the Chemistry of Proteid^,

Part I. Journ. of Physiol., 1901-2, xxvii. 418.
P. A. LEVENE and L. B. MENDEL. Some Decomposition Products of the

Crystallized Vegetable Proteid edestin. Amer. Journ. of Physiol., 1902, vi.

48.
A. N. RICHARDS and W. J. GIES. Chemical Studies of Elastin, Mucoid, and other

Proteids in Elastic Tissue, with some Notes on Ligament Extractives.

Amer. Journ. of Physiol., 1902, vii. 93.
W. W. LESEM and W. J. GIES. Notes on the Protagon of the Brain. Amer.

Journ. of Physiol., 1903, viii. 183.
F. G. HOPKINS and S. W. COLE. A Contribution to the Chemistry of Proteids,

Part II. Journ. of Physiol., 1903, xxix. 451.
W. CRAMER. On Protagon, Cholin, and Neurin. Journ. of Physiol., 1904, xxxi.

30.
C. SEIFERT and \V. J. GIES. On the Distribution of Osseo-mucoid. Amer.

Journ. of Physiol., 1904, x. 146.
H. NEILSON. The Hydrolysis and Synthesis of Fats by Platinum Black. Amer.

Journ. of Physiol., 1904, x. 191.
H. G. WELLS. On the Relation of Autolysis to Proteid Metabolism. Amer.

Journ. of Physiol., 1904, xi. 351.
E. R. POSNEII. Do the Mucoids combine with other Proteids ? Amer. Journ. of

Physiol., 1904, xi. 404.
P. A. LEVENE. The Autolysis of Animal Organs. Amer. Journ. of Physiol.,

1904, xi. 437 and xii. 276.
T. B. OSBORNE and I. F. HARRIS. The Precipitation Limits with Ammonium

Sulphate of some Vegetable Proteins. Amer. Journ. of Physiol., 1905, xiii.

436.
T. B. OSBORNE and I. F. HARRIS. The Solubility of Globulin in Salt Solution.

Amer. Journ. of Physiol., 1905, xiv. 151.
H. C. HASLAM. The Separation of Proteids. Journ. of Physiol., 1905, xxxii.

267.
R. H. A. PLIMMKR. The Formation of Prussic Acid by the Oxidation of Albumins.

Journ. of Physiol., 1904, xxxi. 65 ; and 1905, xxxii. 51.
P. A. LEVENE. The Cleavage Products of Proteoses. Journ. of Biolog. Chem.,

1905-6, i. 45.

E. R. POSNER and W. J. GIES. Is Protagon a Mechanical Mixture of Substances,

or a definite Chemical Compound ? Journ. of Biolog. Chem., 1905-6, i. 59.
H. D. DAKIN. The Oxidation of Amido-acids with the Production of Substances

of Biological Importance. Journ. of Biolog. Chem., 1905-6, i. 171.
A. E. TAYLOR. On the Synthesis of Protein through the Action of Trypsin.

Journ. of Biolog. Chem., 1907, iii. 87.
T. B. ROBERTSON. Note on the Synthesis of Protein through the Action of

Trypsin. Journ. of Biolog. Chem., 1907, iii. 87.
C. H. NEILSON. Further Evidence on the Similarity between Catalysis and

Enzyme Action. Amer. Journ. of Physiol., 1905-6, xv. 148.
C. H. NEILSON. The Inversion of Starcli by Platinum Black. Amer. Journ.

of Physiol., 1905-6, xv. 412.
W. B. HARDY. Colloidal Solution. The Globulins. Journ. of Physiol., 1905-6,

xxxiii. 251.
R. H. A. PLIMMER and W. M. BAYLISS. The Separation of Phosphorus from

Caseinogen by the Action of Enzymes and Alkali. Journ. of Physiol., 1905-6,

xxxiii. 439.

F. G. HOPKINS and E. G. WILLCOCK. The Importance of Individual Amino-acids

in Metabolism. Journ. of Physiol., 1906-7, xxxv. 88.

W. M. BAYLISS. Researches on the Nature of Enzyme Action. Journ. of Physio .,
1907-8, xxxvi. 221.

j LIVING MATTEK 41

W. M. BAYLISS. The Nature of Enzyme Action. London, 1908.

P. HARTLEY. On the Nature of the Fat contained in the Liver, Kidney, and

Heart. Journ. of Physiol., 1907-8, xxxvi. 17.
O. ROSENHEIM and M. C. TEBB. The Non-existence of " Protagon " as a definite

Chemical Compound. Journ. of Physiol, 1907-8, xxxvi. 1.
H. D. DARIN. Comparative Studies of the Mode of Oxidation of Phenyl Derivatives

of Fatty Acids by the Animal Organism and by Hydrogen Peroxide. Journ.

of Biolog. Chem., 1908, iv. 419 ; and 1908-9, v. 173, 303.
R. H. A. PLIMMER and F. H. SCOTT. The Distribution of Phospho-proteins in

Tissues. Trans. Chem. Soc., 1908, xciii. 1699.
A. E. TAYLOR. On the Synthesis of Protamin through Ferment Action. Journ.

of Biolog. Chem., 1908-9, v. 381.
A. E. TAYLOR. On the Composition and Derivation of Protamin. Journ. of

Biolog. Chem., 1908-9, v. 389.
T. B. ROBERTSON. On the Synthesis of Paranuclein through the Agency of

.Pepsin, etc., etc. Journ. of Biolog. Chem., 1908-9, v. 493.
R. H. A. PLEMMER and F. H. SCOTT. The Transformations in the Phosphorus

Compounds in the Hen's Egg during Development. Journ. of Physiol., 1909,

xxxviii. 247.
T. B. OSBORNE, LEAVENWORTH and BRAUTLECHT. The Different Forms of

Nitrogen in Proteins. Amer. Journ. of Physiol., 1908-9, xxiii. 180.
R. H. A. PLIMMER and R. KAYA. The Distribution of Phospho-proteins in

Tissues, Part II. Journ. of Physiol., 1909-10, xxxix. 45.
E. V. McCoLLUM. Nuclein Synthesis in the Animal Body. Amer. Journ. of

Physiol., 1909-10, xxv. 120.

CHAPTEK II

LIVING MATTER: ITS FUNDAMENTAL PROPERTIES

CONTENTS. — Vital metabolism and phenomena of nutrition and reproduction.
2. Vital metabolism and phenomena of excitability and sensibility. 3. Laws of
stability and variability of living species. Critical examination of Theory of
Evolution ; Darwinism, and Neo-Lamarckism. 4. Evolutionary theories of Nageli,
Weismann, De Vries. 5. Distinctive characters of plants and animals : (a} Doc-
trine of Linnaeus ; (b) doctrine of Cuvier ; (c) doctrine of J. R. Mayer, Dumas,
Liebig. 6. Different forms of plant and animal metabolism : (a) Nitrifying
bacteria ; (6) green plants ; (c) a-chlorophyllous plants ; (d) herbivorous and
carnivorous plants. Bibliography.

THE fine morphological organisation and highly complex chemico-
physical structure of elementary organisms, while sufficiently
distinctive in character to differentiate non-living matter from
living bodies, are not adequate to distinguish the living body from
the dead, or from the products elaborated by the living. As a
matter of fact, our knowledge of cytological structure depends
mainly, and the data we possess in regard to the chemical composi-
tion of the cell depend entirely, upon observations made on the
dead organism.

Yet it is upon the cytological and physico-chemical structure
of the cell that the physiological activity and functions common
to all living beings are founded, and it is by these that they are
characteristically distinguished from non-living matter.

General Physiology has of late undergone a remarkable
development in the direction of philosophical interpretation. We
must here confine ourselves to summarising the most definitely
ascertained conclusions — passing over the many hypotheses by
which it is attempted to fill the unbridged gaps, and keeping
strictly to what may serve as the foundation of scientific culture,
and preparation to the study of human physiology.

I. Life is essentially characterised by instability and movement,
by the constant transformation of matter, with a corresponding
evolution and accumulation of energy, which is exhibited in uni-
cellular as in multicellular organisms, in plants as in animals.
The name Metabolism (/zcra/^oA.?/, change) has been given to these
physico-chemical changes of living protoplasm as a whole. It is

42

CHAP, ii LIVING MATTER 43

the result of two opposite processes, which are continually super-
posed and succeed each other : a synthetic, assimilative, and con-
structive process, known as anabolism, and an analytical, dissimila-
tive, and destructive process, known as katabolism.

In the anabolic process, the cell forms or elaborates organic
matter from the nutrient materials, by the aid of energies derived
from the environment or developed by oxidation of its own
substance ; it takes up this organic matter by intussusception,
transforms it into living protoplasm, or stores it as reserve
material.

In the katabolic process, the cell breaks up and uses the
reserve materials, disintegrates its own protoplasm, and returns
to the environment the products of decomposition, combustion,
and activity.

While the two opposite processes which constitute metabolism,
or the exchanges of matter and energy, are intimately connected,
they are differently distributed in the two principal phases of life,
the progressive and the retrogressive. During the first phase the
organism grows and develops, and is active in its functions;
during the second, it dwindles and degenerates, and its functions
are abated. The characteristic phenomena of nutrition, growth,
and development in the organism are the natural consequences of
metabolism, where the assirnilatory or anabolic processes prepon-
derate ; so, too, atrophy, senility, and death result from predomin-
ance of the dissimilatory or katabolic processes, when life is on the
wane.

Between the progressive and retrogressive phases of life,
between youth and age, there lies a long intermediate period,
during which the two opposite processes, anabolic and katabolic,
are practically in equilibrium. This is the phase of maturity,
characterised by the full and vigorous exercise of all the vital
functions, more particularly of the reproductive capacity.

It is only when growth and ontogenic development are com-
plete that the organism is able to reproduce itself. In other words,
only when the factors or hereditary tendencies accumulated within
the germ from which the organism has arisen, have become per-
fectly developed and active, is it capable of forming by itself or
by intercourse with an individual of the opposite sex, new germs,
i.e. new aggregates of hereditary elements adapted for reproduction
and conservation of the species.

Metabolism is the invariable physiological basis of these
marvellous phenomena : when the anabolic process predominates,
the hereditary tendencies contained in the germ develop and
become active; when the evolution of the individual is com-
plete, the metabolic process is turned to preparing the hereditary
material of new organisms.

II. Metabolism as the exchange of matter between organism

44 PHYSIOLOGY CHAP.

and environment is intimately connected with metabolism as
exchange of energy. Each living organism contains within itself
at any given moment of its life a sum of potential energy, drawn
from the sun's rays, and from the food-stuffs which it has ac-
cumulated or assimilated ; and this energy is always ready to
discharge itself, or explode by transformation into kinetic energy,
in consequence either of internal impulses or of external stimuli.
The most striking form assumed by the energy developed in a
living organism is the movement of masses, the power of surmount-
ing resistance, i.e. of doing mechanical work. When these move-
ments or changes of form or position in space depend upon internal
stimuli they appear to be spontaneous or automatic, and are the
most common and obvious objective sign that the organism that
accomplishes them is living. When they are provoked by external
stimuli they appear as reflex movements, i.e. as the effects of
internal reactions to external stimuli ; in that case there is a
striking disproportion between action and reaction, although this .
is not a distinctive sign of life, since the same may be observed in
many chemical combinations — the so-called explosives. What
does, however, differentiate the latter from living substances, is
that the chemical activity of explosives exhausts itself in the
explosion, while the organism becomes fatigued with work, and
recuperates in repose, i.e. at each reaction it only discharges part
of its energy, and during the functional pauses it recovers by the
-anabolic process the quantity of potential energy that has been
consumed.

This peculiar capacity for developing, spending, and reaccum-
ulating energy, which characterises living beings, has received
the name of Excitability, and is distinguished as reflex or auto-
matic, according as the reactions or excitations are provoked by
internal tendencies or impulses, or by external stimuli, or excita-
tions extrinsic to the organism.

That there must be a marked analogy between the internal
conditions of automatic, and those of reflex excitability, appears
from the fact that it is often very difficult to differentiate objec-
tively between automatic movements and reflexes; on the other
hand, many movements originally automatic become reflex by
a simple morphological evolution of the elementary organism
that produces them, while many originally reflex movements
become automatic by long exercise and habit.

These phenomena of excitability, which can be observed under
various forms in all living organisms, are intimately connected
with another group of phenomena, that can be directly observed
upon ourselves alone, since they are accessible only to immediate
internal observation or introspection. These last are the psychical
phenomena, which as a whole constitute the content of con-
sciousness.

ii LIVING MATTER 45-

The most rudimentary forms of consciousness, and as such the
most widely dispersed (common, it may be, to all living beings), are
represented by the phenomena of Sensibility, taken in the true
psychological and not in the metaphorical sense — which is invari-
ably intended by physicists in speaking, e.g. of the sensibility of
the balance, galvanometer, or thermopile.

Certain physiologists, including Claude Bernard, have con-
sidered sensibility to be the highest form, or evolutionary product,
of excitability, i.e. of the physiological property common to all,
even elementary, organisms of reacting to stimuli according to-
their nature. This, however, is either to disallow the psychical
import of the word sensibility, or to admit as a fact that which is
wholly inconceivable, i.e. the emergence of any psychical pheno-
menon— even in the form of vague internal sensations — from
simple molecular movements. According to our physiological
concepts, sensibility and excitability do but express the same thing
from two different standpoints. " Excitability is for us sensibility
expressed in a verbal symbol suggested by external observation ;
sensibility is the same excitability expressed in a verbal symbol
derived from introspection. If we denote by excitation and
sensation the effects corresponding, respectively, to excitability and
sensibility, then excitation is the objective or material aspect
of sensation ; sensation is the subjective or psychical aspect of
excitation " (Luciani, 1892).

This is merely a formal statement of the fundamental hypo-
thesis of psychophysics, viz. that psychical phenomena are the
correlatives of physiological phenomena, and express the aspects-
under which the latter surge up in consciousness, and form its
content. From the objective standpoint, psychical phenomena
also must be regarded as so many forms of excitation, determined
by the metabolism of the protoplasm, which is the common physio-
logical basis of all vital phenomena.

III. In fulfilling the functions of nutrition, reproduction,
excitability, and sensibility, all plant and animal organisms are
subject to two laws, which to a certain extent are antagonistic, the
Law of Heredity, and the Law of Variation. The first represents
the principle of Stability, the second the principle of Evolution.
Neither the one nor the other are to be understood in an absolute
sense, since they are mutually exclusive, but it is extremely
difficult to fix the precise limit between stability and variability,
as appears from the history of biological science.

Until some half-century ago the mind of most naturalists
was dominated by the law of stability, Fixity of Species being
a dogma, solemnly proclaimed by Linnaeus in his famous
aphorism " Species tot sunt quot diversas formas ab initio produxit
infinitum Ens" (Philosophia botanica, 1751).

A little more than a century later, in 1859, the publication of

46 PHYSIOLOGY CHAP.

Darwin's book On the Origin of Species by Means of Natural
Selection caused a radical change in the ideas of the naturalists,
and led to the almost unconditional triumph of the law of evolu-
tion, to the detriment of the law of stability. The evolutionists
fell into excesses, even denying the existence of biological species.
We have recently entered upon a period of acute criticism of old
And new theories of the Origin of Species, and at present the con-
viction is gaining ground that none of these theories has an
absolute demonstrative value, all having rather the significance of
hypotheses that are of great use to the biologist in orientating
himself in his positive researches.

The idea of evolution has till now been the only conception
imagined by the naturalists to account for the evident affinity
exhibited among themselves by the different plants and animals
which are grouped into species, genera, families, orders, classes.
In all these groups a certain conformity of morphological type is
apparent.

According to the Evolutionary Theory, this unity of type is
the expression of a unity of origin (monophyletic origin), from
which the various families, genera, and species, animal and veget-
able, have been derived by successive differentiations. Compara-
tive anatomy, embryology, palaeontolog'y, botanical and zoological
geography, offer numerous facts that accord perfectly with the
theory of evolution. With the progress of biological science,
however, other data have gradually emerged that are difficult to
reconcile with the concept of simple, continuous, monophyletic
evolution.

Many of the resemblances, analogies, and hornologies admitted
by comparative anatomists up to a few years ago are no longer
valid in face of a more profound and exact knowledge of the true
structure and function of certain organs that were previously
imperfectly known. For embryologists, the value of the so-called
" great biogenic law " that was held by certain naturalists to be
one of the fundamental proofs of evolution, has depreciated owing
to the many exceptions which it presents. Further, the analogy
between the development of the individual (ontogenesis) and the
development of the species (phylogenesis) is essentially different,
since the cell-ovum from which the individuals of the evolved
species originate differs entirely from the ovum of the Protista, and
must in itself (by a still incomprehensible mystery) contain the
whole of the determinants of the complex final development,
determinants that are obviously wanting in the ovum of Protista,
or are contained there in a far less degree.

Nor, again, have recent palaeontological data provided all the
arguments in favour of the theory of evolution that were claimed •
a few years ago. Nowadays we can no longer invoke insufficiency
of material to explain the great lacunae found in the development

ii LIVING MATTEE 47

of fossil plants or animals. Species, genera, families are seen to
disappear incontinently, and other species, other genera, other
families are substituted for them, with no evidence of that
continuity and regularity of development which is demanded by
the theory of evolution. Even when continuity of development
is observed for any given organ (e.g. the foot of Solidungula), it is
more apparent than real, since it has been arrived at by observing
a single organ apart from all the other organs which constitute
the species under consideration.

Finally, it should not be forgotten that the fundamental
basis for a complete and satisfactory theory of the evolution of
the entire organic world, in virtue merely of the elements and
forces of the inorganic world (as the pure evolutionists maintain
with Spencer), is still wanting, viz. the demonstration of the
spontaneous generation of life from inorganic matter and force.
The greater the progress made by science, the more do the
organisms believed to be simple appear complex, and the more
improbable is spontaneous generation.

Notwithstanding this and other serious difficulties, it must be
admitted that the hypothesis of evolution has proved in practice
to be a tool of remarkable utility. It has enabled us to gather
up under one concept an infinite variety of scattered facts which
would otherwise have escaped the researches and analysis of
modern science, and thanks to which our positive knowledge has
made extraordinary progress.

Even if all biologists agree in admitting the theory of Evolu-
tion, this harmony ceases when we attempt to determine its
mechanism, i.e. its real causes and factors.

The Darwinians and the so-called neo-Darwinians consider
natural selection to be the principal, if not the sole factor in
evolution, while the Lamarckians and the neo-Lamarckians almost
entirely deny the value of selection, and assert on the contrary
that transformation of species is the result of direct adaptation to
the variable conditions of environment.

Darwin and all his modern followers, while they defend the
principle of selection to the hilt, are forced to admit an innate
tendency to variation within the species, without being able to
indicate its causes. If the said variation is slow, continuous,
gradual and indefinite, as supposed by Darwin, this does not
explain how the appearance of a variation can turn to the advan-
tage of the species, and give opportunity for selection, in such
a way as to favour the individual or individuals in which the new
variation originates, in the struggle for existence, to the prejudice
of the other individuals deprived of the same minimal variation.

On the other hand, the concept of variability of species, both
in plants and animals, has made considerable progress. In the
time of Darwin a pure speculation, it is now a positive experi-

48 PHYSIOLOGY CHAP.

mental fact ; and the new biometric methods have led to the
discovery of facts and laws of capital importance which throw
fresh light on the problem of the origin of species, showing it to
be far more complex and difficult than had been supposed.

These laws demonstrate the necessity of carefully distinguishing
between variation and variation.

Some variations are merely quantitative and fluctuating, and
when studied by the statistical method are found to be subject to
the so-called Law of Quetelet. Such variations are in strict
relation with the nutritive conditions, or with the environmental
conditions in general, and when these change, the values of the
said variations change also, since they are not in themselves
hereditary ; but the individuals that exhibit them return to the
normal type whenever the conditions of the environment again
become normal. It is clear that such variations can have no
importance in determining a transmutation of species.

Other variations, on the contrary, are qualitative and non-
nuctuating, and are not subject to the Law of Quetelet. They are
fixed, independent of the condition of the environment, and should
in reality be termed not variations, but typical hereditary forms,
or again elementary species (or races). Each of the classical
Linnaean species comprises a greater T)r less number of such ele-
mentary species, which in the first instance were confused with
the fundamental typical species, and were erroneously held to
be simple variations of the same. The majority of our plants
and domestic animals are examples of these elementary species.
Selection, as practised artificially by man, or effected by Nature
in the struggle for existence, is of great importance in the sifting
of such elementary species as are more suited to the needs
of man, or better adapted to the environmental conditions. It
would, however, be a great mistake to think that these elementary
species were created and formed by means of selection. In reality
selection did nothing more than seal and set in evidence what
already existed in a mixed and confused state in the fundamental
species, and it created nothing new. Hence the majority of the
examples cited by Darwin from .plants and domestic animals are
of no value as evidence of the agency of selection in the formation
of new species. It is on this account that many speak to-day of
a crisis in Darwinism, when this means the theory of selection
in a restricted sense, and is not a synonym of evolution.

The falling-off in the supporters of Darwinism (in this limited
sense) has reinforced the adherents of Lamarckism, who attribute
the origin of species directly to the environment, to the action
of external causes, climate, soil, nutrition, etc. According to
Lamarck's original idea (1809), it is the want that creates the
organ, which then becomes gradually perfected by use, while with
disuse the organ atrophies and disappears. This idea presupposes

ii LIVING MATTER 49

a teleological principle, regulating the transmutation and adapt-
ability of the new organ, a principle in sharp contrast with the
canons of the materialistic doctrine, which seeks for the mechanical
causes of phenomena, and excludes all mystical, transcendental
interpretations. The neo-Larnarckians renounce the teleological
principle, on the strength of recently acquired data as to the
determining action of certain external agents, e.g. light, heat,
water, gravity, chemical substances, action of parasites, mechanical
action (photomorphosis, thermomorphosis, hydromorphosis, geornor-
phosis, chemomorphosis, biomorphosis, mechanomorphosis, etc.).
This field of research, as cultivated especially by the modern
botanist, is one of the most fruitful to the progress of biological
science.

At the same time it must be remembered that the external
agent, e.g. light or heat, which determines a modification in
the structure and conformation of an organ, is not the true cause
of such a modification, but is rather the external stimulus adapted
to develop a variation which already existed potentially in that
organ. The determining agent, therefore, creates nothing new, it
only stimulates the species to the expression of those properties
which it already possesses potentially. This conclusion, which is
inevitable in the present state of our knowledge, must obviously
limit to a great extent (some even say reduce to zero) the value of
the direct action of external agents in the formation and trans-
formation of species.

But further : in order that the influence of the environment in
the production of new characters in a species shall be efficacious
and enduring, it is necessary to presuppose that the newly acquired
characters are hereditary. Does any such heredity really exist ?

This is one of the problems most keenly discussed among
modern biologists. It is obvious that a decidedly negative reply
would cause the whole edifice of the Lamarckitrin and neo-
Lamarckian theory to crumble. But no one is yet in a position
to give a definite answer. The majority of the facts that were at
one time cited in proof of the heredity of acquired characters have
been triumphantly refuted by Weismann. Some few data relating
to the lower organisms (Bacteria and Saccharomyces) remain, in
which the heredity of newly acquired characters seems to be de-
monstrated ; but how far these data are of value in the solution
of the general problem with which modern biologists are so-
engrossed, is a matter for discussion.

For the present it must be confessed that with the exception of
these few cases among the inferior organisms, all the attempts
hitherto made to obtain new forms of plants and animals by the
effect of one or several external causes have given negative results.

IV. Starting from a profound criticism of Darwinism and
Lamarckism, Nageli (1881?) founded a new theory of evolution,,

VOL. I K

50 PHYSIOLOGY CHAP.

according to which the origin of species depends upon the intimate
constitution of the germinal matter (or idioplasm), inasmuch as
this possesses an inherent tendency to perfect itself and to progress,
developing by a slow and continuous evolution new and more
complex forms, which are independent to a certain degree either
of • the variations of the environment or of the struggle f9r
existence.

It is undeniable that all the branches of the zoological trunk
exhibit a progression from the lower forms to the higher, and
always in a sufficiently cognate form, although the animals may
be subjected to very different external conditions of existence and
development. We see, for instance, that the eye, which in. the
rudimentary species of animals is represented by a simple spot of
pigment, is provided in worms, in arthropods, in molluscs, in
vertebrates, with accessory apparatus, such as the lens, the vitreous
body, iris, choroid, etc. This tendency towards perfection, whether
of single organs and apparatus, or of the individual as a whole,
which is revealed everywhere in the organic world, must, according
to Niigeli (since it is comparatively independent of extrinsic vital
conditions), find its explanation in the very being of the living
substance.

Unlike Darwinism and Lamarckism, which accord a pre-
dominating importance to external causes in phylogenic evolution,
Nagelism assigns the maximal importance to internal causes.
Nageli's phylogenesis harmonises perfectly with his ontogenesis.
The internal causes of the transformation are perfectly analogous
to those by which the germ, or fertilised ovum, develops into the
perfect individual, and the mutilated individual is capable of
regenerating a missing member (e.g. a pollarded tree can recover
all its branches, a lizard can reproduce its lost tail, a decapitated
snail can reproduce its head). It is certainly within the intimate
physico-chemical structure of the idioplasm of the egg, or
mutilated individual, and not in the environment, that we must
seek the determining cause of the individual development or
reintegration. So likewise the determining causes of the
mutability of species, and of the slow formation of new and ever
more perfect species, must lie not in the environment, but in the
intimate structure of the idioplasm.

As in ontogenic evolution the environment, in addition to
nutritive matters, provides a sum of stimuli favourable to the
development of hereditary tendencies ; so in phylogenic evolution
the environment provides impulses favourable to the development
of creative tendencies, and in measure as these develop, moulds and
modifies them, adapting them to the circumstances.

It is not our task to follow Nageli in the development of his
theory. From the standpoint of general physiology, it suffices to
show that it harmonises perfectly with the principle we have

ii LIVING MATTEE 51

formulated in regard to the elementary vital activities, which are
all centred in metabolism. Both the reproductive capacity, by
which the hereditary tendencies are rapidly completed, and the
evolutionary capacity, by which the creative tendencies slowly
develop, are founded upon the metabolic processes of living
protoplasm.

The same difference that we have seen to exist between
automatic activity as depending essentially on internal impulses
and tendencies, and reflex activity as due to external stimuli,
exists between Nagelism and neo-Lamarckism.

Starting from the psycho-physical theorem that conscious
psychical phenomena are the introspective aspect of correlative
physiological excitations, it is not too bold to assume that
unconscious physiological phenomena likewise have a psychical
aspect which is not clearly revealed to introspection, although it
helps to build up the content of consciousness. With this premise,
it seems reasonable to admit with Hering that ontogenic pheno-
mena are the correlatives of an unconscious memory inherent in
the protoplasm ; just as phylogenic phenomena might be considered
the correlatives of an unconscious formative imagination.

Weisinann (in 1892) attempted a sort of reconciliation between
Darwinism, Lamarckism, and Nagelism by assuming that the
action of external causes might be fixed in the species, and become
hereditary, if the said action were exercised on the plasma of the
germinal cells. The modifications suffered by these would manifest
themselves in the embryo and the adult individual, and would be
transmitted to the descendants. In this way what Weisinann
calls germinal selection would become possible, in which the action
of external agents, combined with natural selection, would deter-
mine the origin of new species.

These, however, are merely ingenious abstract speculations,
which more or less successfully disguise our impotence to determine
in any precise and accurate manner the relation between the action
of external causes and the reaction of internal causes, manifested
in the development of a morphological process.

De Vries (1901) thought to escape from the many and
insuperable difficulties of the hypotheses we have been examining
by his Theory of Mutations, according to which new species
originate not in a continuous variation, but in discontinuous
variations, by sudden leaps which he termed mutations. In
certain moments of the life of the species, under special conditions,
some individuals may unexpectedly assume a series of new
characters, differing from those possessed by their progenitors, and
these characters might be hereditary.

Many well-known facts in the history of plants and domestic
animals seem to prove the sudden origin of new forms, as supposed

52 PHYSIOLOGY CHAP.

by the theory of De Vries. The majority of the new varieties
cultivated in the fields, orchards, and gardens, when not obtained
by hybridising, appear to have originated in such unexpected
mutations.

These facts were illustrated and described, even before De Vries,
by Korschinski, who gave the phenomena the name of heter agenesis.

De Vries in his famous experiments at the Botanical Garden of
Amsterdam saw several distinct species originate in a few years
from Oenothera Lamarckiana — Oenothera gigas, 0. albida, 0.
rubrinervis, 0. nanella, etc., species which are said to give rise
on direct fertilisation to products of a constant character. This
would be the first experimental instance on record of neo-genesis
in species belonging to the higher organisms. Not all biologists,
however, are inclined to accept the conclusion of De Vries. Many
(among them Bateson, and Cuboni in Italy) maintain that the
so-called new species have no constant characters of descent, and
that the new forms observed by the illustrious botanist of
Amsterdam represent merely special cases of polyhybridism, in
which the dominant and recessive elements of the progenital
forms separate out according to Mendel's Law. In favour of this
supposition we have the fact that some of the pollen grains of
Oenothera Lamarckiana are deformed and sterile, as always occurs
with hybrids.

If we admit that the mutations observed by De Vries are no
more than a return to the parent species, the fundamental basis
of his theory loses all evidential value. Further, it is undeniable
that many facts of systematic botany, and above all of palaeontol-
ogy, can be more readily interpreted on the generally accepted
theory of continuous variations. And lastly, it should be noted
that De Vries himself recognises that the all-essential point, i.e.
the internal causes of mutation, still remains an impenetrable
mystery to human investigation.

Whatever the future of the different theories relating to the
mechanism by which the various living forms have developed one
from another, whatever the nature of the internal causes deter-
mining the formation of new species, it must never be forgotten
that the Law of Descent, i.e. the general Theory of Evolution, which
by means of Darwinism dominated the minds of scientific men
for half a century, has been marvellously fecund, and has incited a
vast series of researches, leading to the acquisition of new truths,
which without that theory might never have been gathered up.
It therefore remains the corner-stone of biological research ; even
more than as a hypothesis we are constrained to admit it as a
necessary postulate, because its negation would logically include
the negation of a unitary biological science.

. From the foregoing observations on the vital activities common

ii LIVING MATTEE 53

to all living beings, we may formulate the following general
propositions : —

(a) All vital activity is founded on the metabolism of living
matter.

(&) As a material exchange, metabolism expresses itself in
anabolic and katabolic processes.

(c) As a dynamic exchange, metabolism manifests itself by the
accumulation and discharge of energy.

(d) The anabolic and katabolic processes express themselves
in the phenomena of nutrition (consumption and repair) and
reproduction (formation and evolution of germs).

(e) The accumulation and transformation of energy is exhibited
in the phenomena of rest and excitation (automatic or reflex in
character).

(/) All the processes of vital metabolism conform to the
conservative laws of heredity, and to the evolutionary laws of
variability.

(g) Vital metabolism is exhibited under a double aspect :
to external observation it manifests itself in somatic phenomena ;
to introspection it reveals itself in psychical phenomena, conscious
and unconscious.

V. On penetrating deeper into the study of common vital
activities, we must inquire whether, from the standpoint of general
physiology, it is possible to differentiate sharply between the two
great kingdoms of living nature — plants, and animals.

In comparing what are relatively the highest representatives
of the two kingdoms, nothing seems more, simple and natural than
the distinction between a plant and an animal. Many erroneous
opinions have, nevertheless, been promulgated in the attempt to
define their differential characters. Of these the principal are as
follows : —

According to Linnaeus, the lack of sensibility and capacity
for active movement in plants is sufficient to distinguish them
from animals. But the case of Mimosa puclica (Fig. 9), Dioneci
muscipula (Fig. 10), and other sensitive plants, whose leaves
move at the slightest contact with an insect, show that excitation
in the form of active movement, the external sign of sensibility,
is demonstrable in plants also. Claude Bernard (1878) showed
that anaesthetics (ether and chloroform) act in the same way on
animals and on sensitive plants.

Cuvier was of opinion that the existence in animals of a
distinct digestive apparatus with the accompanying digestive
function, of which no trace exists in plants, was a sufficient sign
of distinction between the former and the latter. To-day, however,
we know that an immense number of the lower animals have no
digestive tube, while on the other hand the so-called insectivorous
plants, described by Darwin, possess organs capable of subjecting

54

PHYSIOLOGY

CHAP.

animal substances to a real digestion. Papain, an enzyme which
has the same properties as pepsin, has been extracted from Carica

w"

!•'!<;. 0. — Mlinom pinlicn. During the day the leaves are extended, as^in A ; when stimulated
by .shaking or touching, they close up, drooping backwards, as la /.'. After chloroform
narcosis this reaction does not take place.

papaja. The juices of the leaves of Nepenthes, Drosera, and Dionea
(Figs. 11 and 12) digest meat to the great advantage of the plant.
We know further that plants, like animals, accumulate sugar,

starch, oil, and proteins
as reserve nutritive ma-
terials, and, for nutritive
purposes and to bring
them into circulation,
submit them to a regular
digestion by the action
of certain enzymes, such
as diastase, invertin,
emulsin, and the peptic
or hydrolytic ferments.

After Lavoisier (1777)
had demonstrated that
animals absorb oxygen
and exhale carbonic acidr
and the Dutch Ingen-
housz, and almost contemporaneously the Genevans Senebier and
Th. de Saussure (1800), had discovered that green plants reduce
the carbonic acid of the air by assimilating carbon and emitting
oxygen, a theory was involved which predicated a functional
antagonism between plants and animals. By storing up the

Fiu. 10. - - Leaf of Dimiett nm*ripul«. (Darwin.) The
upper surface of the leaf shows the bristles that react
on the slightest contact with an insect, provoking im-
mediate closure of the two halves of the leaf, ami
capture of the insect, which is then digested by the
secretion from the glands upon the surface of the leaf.

II

LIVING MATTER

55

energy of the sun's rays, as observed by J. R Mayer (1845), plants

reduce carbonic acid and form organic sub-

stances, which serve as fuel for the animals ^

that constantly devour the plants and disperse

the energy stored up in them. The plant is

accordingly an apparatus for reduction, the

animal an apparatus for oxidation.

This theory was more particularly devel-
oped in France by Dumas and Boussingault,

in Germany by Liebig. There is between

plants and animals a constant circulation of

matter and exchange of energy. The animal,

by means of the oxygen of the air, transforms

into heat, electricity, or motion the potential

energy contained in the food-stuffs obtained

directly (herbivores) or indirectly (carnivores)

from plants, and produces water, carbonic acid,

ammonia and salts. The plant draws these

ultimate products from the air and soil, and

by means of solar radiation builds them up

into carbohydrates, fats, and proteins. Animal

life as a
whole is
thus sub-
ordinated
to the pre-
existence
and co-ex-
istence of

plant life, the latter being wholly
independent of the former.

This doctrine of vital an-
tagonism between plants and
animals is no less false than the
teaching of Linnaeus and Cuvier,
as was readily demonstrated by
Pfliiger in 1875. It is a fallacy
to assume any radical difference
of function between plant and
animal protoplasm. In the last
chapter we saw that both kinds

Fi«.12.-.Leaf of Drosera rotundifolm (Darwin ) Qf protoplasm differentiate into
The leaf shows numerous pedunculated Jr

glands, each having at its extremity a drop Cells 01' elementary Organisms
of secretion which serves to catch and digest j j -,-1 ,- ii

the insect. endowed with an essentially

analogous structure and com-
position. In considering the vital characters common to all
living beings we recognised both in plant and in animal metabolism

Fj(i. 11. — Ascidiuni of leaf
of Nepenthes. At the-
bottom of the pitcher-
shaped receptacle is seen
the fluid F, secreted by the
glands, in which the ani-
malcules that fall in can
be digested. This figure
is somewhat reduced.

56 PHYSIOLOGY CHAP.

a double process, anabolic and katabolic : the first synthetic, re-
ducing, assimilatory ; the second analytic, oxidising, disintegrative.

The antagonism apparent at the extreme limits of function
between -the higher plants and animals becomes less and less in
proportion as we descend the scale of the two groups of living
beings. On comparing the simplest animal and plant organisms,
it is impossible to trace a sharp line of demarcation between the
two kingdoms. This fact demonstrates their common origin,
according to the Unitary Theory of Life, by which plants and
animals must be regarded as two divergent stems arising from
a common trunk represented by the simplest, or primitive, living
forms, to which Haeckel gave the name of Protista.

The fallacy of this supposed antagonism between the functions
of plants and animals lies in a confusion between the katabolic, re-
spiratory function, chemically represented by processes of oxidation,
which is common to all living beings, and the anabolic, chloro-
phyllic function which is peculiar to the green parts of plants.
Vegetable protoplasm, including that provided with chlorophyll,
breathes like animal protoplasm, i.e. it absorbs oxygen and gives
off carbonic acid, when removed from the action of the sun's rays.
Under the influence of these rays, it breathes in the reverse sense,
i.e. it absorbs carbonic acid and gives off oxygen", because the
reducing function of the chlorophyll, which is actively aroused by
the soLir radiation, exceeds in its activity the respiration proper,
and masks its effects.

It has long been known that the presence of oxygen is almost
always essential to plant as to animal life. As early as 1822, De
Saussure was aware that the most vigorous plants, such as the
Cactus, die quickly when brought into an atmosphere deprived of
oxygen. P. Bert found that wheat germinated less freely in
proportion as the oxygen tension of the air in which it was kept
was lowered.

So, too, when tension of carbon dioxide reaches an excessive
degree it is as harmful to plant as to animal life. It was, again,
De Saussure who demonstrated that plants brought into an
atmosphere of C02 perished. An atmosphere containing \ of
carbonic acid is sufficient to check the germination of most plants ;
accordingly, respiration as an oxidative process is a function as
indispensable to the life of plants as to animals.

The antagonism that is sometimes proposed between plants
and animals is therefore fallacious, and derives from the fact that
the former accumulate the energy elaborated from the sun's rays,
while the latter consume it, or transform it into special forms of
heat and motion.

It is in general true that plants cool the surrounding atmo-
sphere, while animals raise the temperature ; but this is due to the
fact that respiration is not usually very intense in plants, and

ii LIVING MATTEE 57

is associated with a considerable transpiration of water, by which
a large amount of heat is rendered latent, so that the plants
as a rule become cooler than their environment. But when tran-
spiration is checked, or when plants which are breathing actively
are observed, they are found to develop as much heat as animals.
For instance, on bringing together a mass of germinating peas, a
rise of temperature of some 2° C. above the surrounding atmosphere
can be detected ; a rise of 15° C. was measured in the large flowers
of the Victoria Regia.

Lastly, it should be noted that if all animals live directly, or
indirectly, on the elements provided by the vegetable kingdom, it
is not, on the other hand, true that all plants live on the inorganic
substances provided exclusively by the soil, air, and water. A
great number of plants, lacking in chlorophyll, live saprophy tically
at the expense of the organic substances of plant residues and dead
animals, or parasitically at the cost of other living things. Such
are the Schizomycetes and Fungi, properly so-called. As the life
of animals is subordinated to that of plants, so the life of this
innumerable vegetable host is subordinated to that of animals or
other plants.

VI. Since antagonism between the vital activities of plants
and animals is excluded, it follows logically that the functional
differences which exist between the two great kingdoms of living
Nature, and which are very apparent in the higher classes, must
consist in the different manifestations in the two kingdoms of
Metabolism, which underlies all vital phenomena. It is evident
that the anabolic processes are predominantly developed in plants,
the katabolic processes in animals.

The fact above emphasised, that all animals require for their
nutrition organic matters (proteins, fats, and carbohydrates)
already formed by other animals or plants, shows that their
anabolic capacities do not extend to synthesis of these substances
from inorganic materials. The majority of plants, on the contrary,
can live and flourish on exclusively inorganic matter, showing
that their anabolic capacity is strong enough to enable them to
make this synthesis.

The anabolic capacity seems to be most highly developed in
the group of the so-called nitrifying bacteria, which in recent
years have aroused great interest among physiologists. Devoid of
chlorophyll, they are none the less able, independent of the action
of the sun's rays, to form by synthesis all the organic substances
which they require for their development and reproduction, given
the inorganic materials provided by the soil and the air. More
wonderful still, some of them, on closer observation, are found to
be capable of synthetically forming organic nitrogenous matter by
absorption of free nitrogen from the air and soil. Among these is
Clostridium pasteurianum, studied by Winogradsky, which utilises

58

PHYSIOLOGY

CHAP.

carbonic acid or the carbonates of the soil to form carbohydrates,
and free nitrogen to form proteins. No less interesting are the
various forms of Rhizobium leguminosarum, studied by Hellziegel,
Nobbe, Beyerinck, Franck and others, which penetrate the root-
hairs of the common Leguminosae (beans, peas, lupins, trefoils, etc.),
and produce hypertrophy in the form of nodules or tubercles

containing a fungoid mass, consisting
of bacteria for the most part of excep-
tional size, with a less number of normal
form and proportions (Fig. 13). Accord-
ing to the said authors, the rhizobium
lives in symbiosis with the leguminous
plant. The latter provides the bacterium
with carbohydrate ; and the bacterium,
by conversion of the free nitrogen into
an organic form, provides the leguminous
plant with the nitrogenous compounds
required for the synthetic formation of
proteins, thus promoting the general
welfare of the plant.

In the greater number of cases,
however, the assimilation of carbon is an
anabolic function of green plants, which
are capable of reducing the carbonic acid
of the air by means of chlorophyll, under
the influence of the luminous rays of
the sun (particularly of the less refran-
gible red and yellow rays) ; and the
assimilation of nitrogen is, generally
speaking, due in plants to reduction of
the nitrates contained in the humus,
and not to intake of free nitrogen. The
clearest demonstration of this fact is
aforded by . the, ™lti™tion of green

plants in artificial SOUltlOnS which, With

the exception of carbon, contain all the
chemical elements that participate in the formation of living
matter, in the form of combinations of salts. The formula given
by Sachs for this artificial nutrient fluid is as follows : —

Fl

ously provide.! with nodules— the

Water .

Potassium nitrate
Sodium chloride .
Potassium sulphate
Magnesium sulphate
Calcium phosphate
Ferrous sulphate .

1000-0
1-5
0-5
0-5
0-5
0-5
0-005

If a grain of maize is placed in this solution to germinate, the

II

LIVING MATTEE

59

experiment being carried out in a glass jar (as shown in Fig. 14),

the plant, under the influence of light, will develop normally,

flower, and bear fruit. If the iron sulphate

is wanting in the solution, the plant may

live for some time, but its leaves will be

colourless, and under the microscope show-
absence of chlorophyll; if the other salts

are wanting, the plant will not germinate,

or perishes as soon as it develops.

This experiment proves that all the

carbon assimilated by the plant is derived

from the carbonic acid of the air — the

grand discovery of Ingenhousz ; further, it

shows that the assimilation of carbon is

conditioned by chlorophyll, the molecules

of which contain iron ; lastly, the assimila-
tion of nitrogen is due to the reduction

of nitrates, and the assimilation of sulphur

and phosphorus to the reduction of sulphates

and phosphates.

The intimate processes by which the

plant succeeds, by the assimilation of all

these elements, in synthetically forming

organic substances are for the most part
unknown. Thanks,
however, to the work of
Sachs, we know some-
thing of the process of
starch formation in the

green parts, which may be taken as the starting-
point for all other synthetic processes in plants.
In the adult cell, chlorophyll is contained within
special ellipsoidal corpuscles known as chloro-
plasts, which are for the most part found in
ift-3— « great numbers heaped against the parietal proto-
W~T plasm (Fig. 15). After a green plant has been
exposed for a few minutes to full sunlight,
starch granules are seen to appear in the middle
or edge of the chloroplasts, which gradually
increase in size until their volume exceeds that
of the chloroplasts. During the night, when
starch formation is suspended, this accumula-
tion is dissolved by the action of diastatic fer-
ments, and conveyed under the form of sugar

to the parts in which it can be utilised as food material.

Starch represents the principal nutritive reserve material that

accumulates in a solid form in the plant cells in which it is formed.

;. 14. — Zra mais in culture
solution. Mg., grain of maize ;
.S'7!., Sachs' nutrient solu-
tion ; *, cork to support plant
in vertical position.

FIG. 15.— Two leaf-cells of
Funaria hygrometrica.
cl, chloroblasts ; n,
nucleus. Magnification,
300 diameters.

£0 PHYSIOLOGY CHAP.

Many monocotyledons normally exhibit no formation of starch,
but produce sugar in solution ; it is only when this is in excess
that starch in the solid form is manufactured.

The other organic matters, fats and proteins, are formed by
gradual chemical change from the carbohydrates, starch and sugar.
The formation of oil from starch may be directly observed in the
seeds of certain plants. Paeony seeds, for instance, so long as
they are immature, contain only carbohydrates and scarcely any
fat. When placed in moist air, it is found after a time that all
the starch has disappeared by conversion into oil. In many of
the lower plants, e.g. Algae, the first visible product in the cell is
not starch but oil.

Far more complex is the synthesis of proteins and nucleo-
proteins effected by the roots from the carbohydrates and derivatives
of the nitrates, sulphates, and phosphates
of the soil. We know nothing about this
marvellous synthesis, indispensable as it
is to the nutrition and development of
living protoplasm. It is only known that
oxalic acid (C2H204) is frequently formed
as a secondary product, which, in itself
toxic, combines, as it is formed, with lime

FIG. K;. — ceiis of Beer Yeast into an insoluble innocuous salt that
collects in the form of a crystalline
powder round those parts of the plant in
which the formation of proteins and nucleins takes place. It
also seems probable that asparagine (C4H8N203), a soluble and
diffusible ammo-body, is an intermediate product in protein
synthesis.

From the green plants one must, in virtue of their metabolism,
distinguish all those plants which are lacking in chlorophyll, and
live as saprophytes, or parasites, or again as parasites and sapro-
phytes according to circumstances. The innumerable host of
fungi and bacteria come under this category. They have the
singular property of consuming in their nutrition and reproduction
only the minimal part of the organic matters which form their
food, and of destroying all the rest by processes of fermentation
and putrefaction, effected by enzymes contained within the cell or
secreted from without.

A classical example of this mode of metabolism is afforded
by Saccharomyces cerevisiae (Fig. 16), which produces alcoholic
fermentation of glucose according to the equation :

When a certain quantity of yeast is introduced into grape
juice, there is formed along with the development of carbonic acid
and the production of alcohol a small amount of glycerin, of

n LIVING MATTEK 61

succinic acid, and of various ethers, which eventually inhibit
fermentation and bring it to a standstill. The quantity of yeast
which is then deposited at the bottom of the vessel is conspicuously
augmented, showing that the cells of the Saccharomyces have
abundantly reproduced themselves; but the organic nutritive
matters contained in the grape juice would, if they had not been
decomposed by the fermentative process, have sufficed for the
nutrition and multiplication of an incomparably larger amount of
yeast.

Many pathogenic or non-pathogenic bacteria are able to dis-
solve gelatin or coagulated albumin for their nutrition and multi-
plication, and effect a putrid decomposition of the various culture
fluids or media, with development of carbonic acid, sulphuretted
hydrogen, ammonium sulphate, ammonia, and a simultaneous forma-
tion of new substances which generally have a toxic action, and are
the cause of virulent disease.

In general those plants that contain no chlorophyll, and require
for their nutriment the organic matters already formed by other
plants or animals, utilise these substances merely as the raw
material of nutrition, submitting them further to special chemical
transformations. Fungi and bacteria, indeed, can adapt previously
inadequate substances to their nutrition. By means of invertase
they transform saccharose into glucose, by diastase starch is turned
into sugar, with the trypsin and pepsin ferments albumin is con-
verted into albumoses and peptone. Fungi have been proved to
nourish in very different culture media, and are capable, with the
help of the organic compounds of carbon, and nitrogenous mineral
salts, of building up synthetically all the highly complex products
essential to the formation of protoplasm. They represent, accord-
ingly, in their metabolism an intermediate group .between the
chlorophyll-containing plants and animals.

The anabolic capacity of all animals, without exception, is
limited to the elaboration of the three principal groups of organic
substances, and their conversion into living protoplasm, with the
further synthetic formation of new substances which do not exist
in the plant world. They are incapable of reducing fully oxidised
organic substances so as to produce carbohydrates, fats, and
proteins; but they have the power (as we shall be able to
demonstrate fully) of transforming carbohydrates into fats, albu-
inoses and peptones into true proteins.

Within the animal kingdom again we can distinguish different
groups, according to their nutritive requirements and correspond-
ing metabolism. Herbivores and frugivores more particularly
need to supplement the proteins with the carbohydrates in which
vegetable food is superabundant ; insectivores and carnivores, on the
contrary, profit by the many fats which abound in animal food.
Neither fats nor carbohydrates, however, are absolutely indis-

62 PHYSIOLOGY CHAP.

pensable to life. Some animals have adapted themselves to a
purely protein diet, and, further, to a single form of the same.
Thus, e.g., the clothes-moth lives exclusively on the keratin of
which the hairs of the wool or fur consist, and from which it
derives all that is necessary for the construction of its protoplasm.
Again, as we shall see, it is possible to keep a dog alive, and in its
normal state, on a purely flesh diet, while this is found impossible
on an exclusive diet of fats and carbohydrates, no matter how
abundant.

The chief part of the mineral substances which enter into the
chemical composition of animals cannot be assimilated as such, but
only when they are present in organic combinations, as, e.g., the
calcium phosphate of milk casein, the potassium salts of muscle
protein. If mice are fed on casein from which the greater part of
the salts contained in the organic combinations of milk have been
previously washed out, and if sugar be added, as well as all the
salts contained in the ashes of milk in a non-organic form, the
mice perish slowly during this diet, and succumb after about forty
days (Lunin). This and similar experiments on artificial feeding
in other animals, show that they are only capable to a small
extent of assimilating inorganic substances, i.e. of binding them
synthetically into the protein molecule on which the living
protoplasm is nourished.

BIBLIOGRAPHY

The following may be consulted for the literature of the Theory of Evolution : — t
LAMARCK. Philosophic zoologique. Paris, 1809.
CHARLES DARWIN. On the Origin of Species by Means of Natural Selection.

London, 1859.

C. VON NAGELI. Mechanisch-physiologische Theorie der Abstammungslehre. 1884.
WKISMANN. Das Keirnplasrne : eine Theorie d. Vererbung. Jena, 1892.
H. DE VRIKS. Die Mutationstheorie. Leipzig, 1901, 1903.
YVES DELAGE. L'Heredite et les grands problemes de la biologie generale. Paris,

1903.

DETTO. Die Theorie d. direkten Anpassung. Jena, 1904.
PAULY. Darwinisnius und Lamarckismus. Munich, 1905.
LOTSY. Vorlesungen iiber Deszendenztheoricn. Jena, 1906.
SCHNEIDER. Einfuhrung in die Deszendenztheorie. Jena, 1906.
RIGNANO. Sur la transmissibilite des caracteres acquis. Paris, 1906.

The two following text-books may be consulted for the general physiology pf
plants, and their characteristics as distinct from animals : —

E. STRASBURGER, F. NOLL, H. SCHENCK, A. F. W. SCHIMPER. Lehrbuch d.

Botanik. Jena. G. Fischer, 5th ed., 1902.

W. PFEFFER. Lehrbuch d. Pnanzenphysiologie. Leipzig, 1897-1901.
Recent English Literature of the subject : —

W. PFEFFER. The Nature and Significance of Functional Metabolism in the Plant.

Proc. Roy. Soc., London, 1898, Ixiii. 93.
K. PEARSON. Data for the Problem of Evolution in Man. Proc. Roy. Soc. , London,

1900, Ixvi. 23, 316.
K.PEARSON. Mathematical Contributions to the Theory of Evolution. Proc Roy

Soc., London, 1900, Ixvi. 140.

ii LIVING MATTEE 63

W. BATESON. Heredity, Differentiation, and other Conceptions of Biology. Proe.

Roy. Soc., 1901, Ixix. 193.

T. M. BALDWIN. Development and Evolution. London & New York, 1902.
A. K. MARSHALL, E. B. POULTON, etc. Five Years' Observations and Experiments

(1896-1901) on the Bionomics of South Africa Insects. Trans. Entom. Soc.,

London, 1902, p. 287.
K. PEARSON. Mathematical Contributions to the Theory of Evolution. Proc. Roy.

Soc., London, 1902, Ixix. 330 ; 1903, Ixxi. 288.
A. R. WALLACE. Darwinism : Exposition of the Theory of Natural Selection with

some of its Applications. London, Macmillan. 1902.
W. F. R. WELDON. Professor de Yries on the Origin of Species. Biometrika,

1902, i. 365.

TH. M. MORGAN. Evolution and Adaptation. New York, 1903.
W. BATESON. Opening Address at the British Association (Zoology). Nature,

•1904, Ixx. 406, 539.
A. D. DARBISHIRE. On the bearing of Mendelian Principles of Heredity on Current

Theories on the Origin of Species. Manchester Lit. Phil. Soc., 1904, xlviii.
A. S. PACKARD. The Origin of the Markings of Organisms (poecilogenesis) due to

the Physical rather than to the Biological Environment ; with criticism of the

Bates-Miiller hypotheses. Proc. Amer. Phil. Soc., 1904, xl. 393.
R. C. PUNNETT. Merism and Sex in spinax niger. Biometrika, 1904, iii. Part

IV., p. 313.
A. E. BROWN. The Utility Principle in Relation to Specific Characters. Proc.

Ac. Nat. Sc., Philad., 1905, Ivii. 206.
E. S. CONKLIN. The Mutation Theory from the Standpoint of Cytology. Sc.,

N.S., 1905, xxi. 525.
H. E. CRAMPTON. On a General Theory of Adaptation and Selection. Journ. of

Exper. Zool., 1905, ii. 425.
C. B. DAVENPORT. Evolution without Mutation. Journ. of Exper. Zool.. 1905,

ii. 137.
W. S. HARWOOD. New Creations in Plant Life : an Account of the Life and Work

of Luther Burbank. New York, 1905.

N. DE VRIES. Species and Varieties. Chicago, Open Court, 1905.
R. H. LOCK. Recent Progress in the Study of Variation, Heredity, and Evolution.

London, 1906, xv. 299 pp.
C. U. MERRIAM. Is Mutation a Factor in the Evolution of the High Vertebrates ?

Science, 1906, p. 241.

CHAPTER III

LIVING MATTER : CONDITIONS BY WHICH IT IS DETERMINED

CONTENTS. — 1. Nutrition the necessary external condition of vital metabolism.
Phenomena of inanition. 2. Importance of water. Latent life and anabiosis.
y. Importance of oxygen. Aerobic and anaerobic life. 4. External temperature
indispensable to life. 5. Total pressure of air and water, and partial pressure of
oxygen and carbonic acid. 6. External stimuli. 7. Chemical stimuli. Cherno-
taxis. 8. Mechanical stimuli. Barotaxis. 9. Thermal stimuli : thermotaxis.
10. Photic stimuli. Phototaxis and Heliotaxis. 11. Electrical stimuli. Galvano-
taxis. 12. The various biological zones of ocean life (Plankton). 13. Internal
conditions and stimuli of metabolism. Theory of automatism. 14. Hypotheses
to explain the intimate mechanism of living matter. Bibliography.

Two orders of conditions, external and internal, are essential to
the maintenance of metabolism. Both the one and the other may
act directly or indirectly. The former cannot fail without cessation
of life, nor the latter without modifications and disturbances of
vital phenomena. If we were acquainted with all the internal and
external conditions of life, the task of Physiology would be
terminated ; the " conditioned," i.e. Life, would be perfectly known
to us.

Not all the vital conditions are essential in the same degree to
every living being. Each organism has special requirements in
virtue of which it lives and flourishes. Each living species, there-
fore, demands special treatment. From the standpoint of general
physiology we have only to consider in broad outlines the most
universal and best known of the vital conditions.

I. The first and most general external condition of metabolism
is Nutrition, i.e. the sum of the chemical materials essential to the
building-up of living protoplasm.

We saw in the last chapter how various were the chemical
forms of the foods necessary to different groups of living beings —
to nitrifying bacteria, green plants, saprophytic and parasitic fungi,
herbivorous and carnivorous animals. To this we may add that
in accordance with the chemical composition of the nutritive
medium, the various elementary organisms react very differently.
Some can only live in fresh water ; others in salt water. All die
more or less rapidly when brought into distilled water. Every

64

CHAP, in

LIVING MATTER

65

simple or complex organism, indeed, exhibits a certain capacity of
adapting itself to an environment and nutrition different from
those to which it has been accustomed, provided only that the
change is effected very slowly and gradually. In consequence of
this adaptation, temporary modifications of the specific characters
ensue. According, however, to certain experiments of Nageli,
these are not persistent, but quickly disappear when the organism
is brought back to its original environment and alimentation.

In order to form an adequate concept of the adaptability of
various organisms to unusual conditions in respect of nutrition,
we . may refer to certain bacteria, recently investigated by
Winogradsky, which he calls sulphur or iron bacteria. The
sulphur bacteria are represented by a family of microbes, which
can only live in the water of bogs or marshes, where, owing to the
decomposition of vegetable and animal matters, there is a great
development of hydrogen sulphide. This they absorb, oxidising it,
and setting free the sulphur, which they accumulate in the body
of their cells in the form of highly refractive granules. On
subsequent oxidation, these granules give rise to a formation of
sulphuric acid, which is excreted as such. The iron bacteria live
in marshy water, where ferrous carbonate is found in solution ;
this they take up, and convert it into ferric carbonate, which readily
decomposes on excretion, and the precipitate of iron oxide forms
the ochre-like deposit known as meadow-ore.

Both sulphur and iron bacteria perish when brought into
spring water, which contains no hydrogen sulphide or ferrous
carbonate, while these compounds act as poisons to all other living
beings. They must, therefore, have undergone a permanent adapta-
tion to a quite exceptional form of environment and nutrition.

Whatever the nature of the food-stuffs appropriate to the
various organisms, they are indispensable to the maintenance of
life. Absolute or relative deprivation
of food produces a state of inanition,
during which the organism primarily
consumes the reserve materials stored
up in the body of the cell, and then
absorbs its own protoplasm, shrinking
more and more, until it finally perishes
when the protoplasm has no longer
enough potential energy to maintain the
balance of metabolism (Fig. 17).

The individual living elements of
which the tissues and organs of the
higher animals are composed draw all
their nourishment from a common fluid,
the lymph, which circulates in the interstices of the tissues.

During inanition, the total consumption of the organism is not

VOL. I F

prived of granules. Magnification,

66 PHYSIOLOGY CHAP.

equally distributed among the different tissues ; a sort of struggle
for existence goes on between them, some being consumed and
liquefied for the benefit of others, which continue to exist as
parasites, and are even able to reproduce themselves (Luciani).
The process of inanition in the higher animals and man wjll,
however, be treated in detail later on.

II. Another condition no less indispensable to metabolism
is water, which infiltrates the living protoplasm in large quantities,
rendering it soft or semi-fluid. In order to realise the importance
of water to the vital functions, we need only consider the
consequences of natural or artificial desiccation in unicellular
organisms. Within certain limits the intensity of metabolism
increases or decreases with the increase or decrease of the water
content of the living matter, while beyond those limits vital
activity ceases altogether. In the great majority of plants,
natural dryness of environment is sufficient to cause death. Many
mosses, lichens and algae, however, which live on naked rocks are
able to support the drought of summer without injury. Seeds
and spores, in particular, when removed from the plant, may be
kept in a dry state without losing their capacity, for germination.
It was formerly stated that the wheat found with the Egyptian
mummies retained its power of germinating after more than two
thousand years; but this fact was disproved by the famous Egypto-
logist Mariette. It has, however, been demonstrated that spores
of mosses and the seeds of Mimosae, kept in a dry state for over
sixty years in a herbarium, were perfectly capable of germination ;
other seeds, on the contrary, lose their vitality after one year,
others again after a few days, while others will not tolerate any
desiccation, e.g. the seeds of Salix.

Some groups of animals can be kept for years in a desiccated
state without losing the faculty of awakening to life a few
moments after they are moistened again (Preyer's anabiosis).
Among these are the so-called Jftoti/erae, small crustaceans, and the
Tardegrada, arachnoids resembling mites, which live in the moss
and dust of roofs, as discovered by Leeuwenhoek (1719), who first
described this remarkable phenomenon. Also the Anguillulae
of mildewed wheat, on which Spallanzani (1776) made many
curious experiments of repeated anabiosis. Lastly, the greater
part of the bacteria, particularly in the spore state, come under
the same category.

It is not easy in any of these cases of apparent death to
determine whether there is absolute suspension of metabolism, a
true latent or potential life, or a metabolism reduced to the
lowest terms, i.e. to the state which Spallanzani was the first to
characterise as minimal life. To decide the question, it is neces-
sary to determine whether these organisms in a state of apparent
death exhibit any trace of respiratory exchange, i.e. of absorption

in LIVING MATTER 67

of oxygen and excretion of C0.2. W. Kochs (1892) used for this
purpose a large quantity of perfectly dry seeds of plants, which he
placed in large glass tubes from which the air had been pumped
out, and which were then hermetically sealed. After many
months, a minute analysis of the contents of the tubes failed to
detect any trace of carbonic acid; and yet the seeds perfectly
retained their capacity for germination. This experiment proves
that it is possible to establish a state of true potential life in the
seeds of certain plants.

The results of a number of experiments undertaken by the
author in collaboration with Piutti (1888) on silk- worm eggs were
somewhat different. Without artificial desiccation these did not
entirely cease to breathe when kept for a long while at a
temperature of 0° C., and even at that temperature they could not
survive prolonged exposure to an atmosphere of pure nitrogen.
When kept for 139 days in conical flasks in which the air was
maintained constantly dry by means of concentrated sulphuric
acid, they perished entirely if the temperature was 9-14° 0., and
partly if it was 0° C. It is therefore clear that under these
conditions the silk-worm eggs are reduced to a state of vita
minima. When placed in glass flasks, in which a perfect vacuum
was produced by the mercury pump, after which they were sealed
up and kept at 0° C., more than half the eggs after 83 days were
alive, and capable of development when brought under normal
conditions of incubation. Here we have evidently a state of
minimal life approximating to that of latent life. Lastly, the
silk-worm eggs were placed under a glass bell-jar, hermetically
sealed to a plate and containing a desiccator with concentrated
sulphuric acid ; when after 128 days the enclosed eggs (which had
shrunk in an extraordinary way from the desiccation) hatched out,
a very copious but incomplete brood of caterpillars was produced,
which were smaller and less lively than the normal. From these
results it seems probable that insect eggs, like plant seeds, can be
artificially brought by desiccation into the state of latent or
potential life. According to Preyer's ingenious comparison, this state
is comparable to that of a clock wound up, but with the pendulum
arrested ; the state of death, on the contrary, is like a clock whicli
can no longer go because its wheels are broken.

III. We saw in the last chapter that plants breathe like
animals, i.e. they take in oxygen, in order by a slow process of
combustion to form carbonic acid and water. The presence of
oxygen is, accordingly, one of the most fundamental conditions in
the active upkeep of metabolism.

This does not mean that the presence of oxygen as such is
indispensable to the maintenance of life. In order to under-
stand its importance we must start with certain general con-
siderations.

68 PHYSIOLOGY CHAP.

Every assimilatory or anabolic process results in an accumu-
lation of energy, and necessarily implies a source of kinetic, which
can be transformed into potential, energy. Each dissimilatory or
katabolic process, on the other hand, results in a dispersion of
energy, and presupposes a store of potential, to be transformed
into kinetic, energy. This is why the two opposite processes are
simultaneous, or constantly and rapidly alternating, during life,
while the two together constitute metabolism, which— as we have
seen — is the physiological basis of all the phenomena of life.

Since in green plants anabolic largely predominate over
katabolic processes, the energy which they develop by oxidation is
inadequate for the synthetic formation of their highly complex
organic substances, and the intervention of the energy derived
from the sun's rays becomes necessary.

In animals, on the contrary, in which katabolic processes
largely predominate, the energy which they develop by the
oxidation of organic substances is not only enough to : yield
mechanical work, and to keep the temperature of the body above
that of the environment, but also suffices to secure the anabolic
processes, or new organic syntheses, by elaboration of the food-
stuffs drawn from plants.

The destruction of the organic molecules by the katabolic pro-
cesses does not take place all at once, so as immediately to turn
combustible substances into final products ; but it is effected
gradually and successively, the more complex being converted
into other less complex molecules, and these into the end-products
rejected by the body.

The presence of oxygen is not essential to all these regressive
metamorphoses. In the absence of free oxygen, protoplasm is able
for a certain time to obtain oxygen from the combinations in
which it is held loosely or firmly, and thus to develop kinetic
energy. The great plasniodia of the Myxomycetes, e.g., if placed in
a medium deprived of oxygen, will continue their movements for
three hours ; ciliated epithelia can live even longer without oxygen
(Engelmann) ; excised frog's muscle placed in an atmosphere of pure
hydrogen will give off carbonic acid for many hours before it
becomes inexcitable (Hermann). Many organisms of the lowest
orders, particularly in the numerous groups of bacteria, have the
faculty of living permanently without oxygen. Pasteur, who was
the first to call attention to this most important phenomenon, gave
the name of anaerobic to the organisms which live in the absence of
oxygen, in contradistinction from the aerobic, which can only
live in presence of this gas. According to Tarozzi (1905), the
incapacity of anaerobic bacteria to develop in culture media in the
presence of oxygen, is due not to a toxic action of the oxygen on
these microbes (as has been stated by many authors) but rather to
chemical modifications of the proteins in the broth used for the

in LIVING MATTER 69

culture. These modifications consist essentially in processes of
oxidation, and the anaerobes appear to be incapable of utilising
highly oxidised proteins in their assimilation. Accordingly, they
can only develop when these substances are once more reduced,
which is effected either by artificially removing the oxygen, or
(after Tarozzi) by adding to the broth a scrap of fresh organ
aseptically prepared, which acts as a reducer, in virtue of the
chemical processes of which it is the seat, and favours the develop-
ment of the anaerobes. In this case it is not necessary to remove
the oxygen before the bacteria can develop. This explains how
such development takes place naturally when these bacteria are in
the presence of tissues of animals that have just died, or, generally
speaking, whenever they find protein matters at their disposal
which have not suffered profound oxidative changes. And this
is why all anaerobes belong exclusively to the class of putrefaction
microbes (saprophytes).

According to the work of Duclaux, Gautier, and Ehrlieh,
anaerobic metabolism may be recognised not only in a great
number of microbes, but in a still greater number of plant and
animal cells.

Many decompositions of organic molecules due to enzyme action
within the cell, or in external secretions, are produced without
intervention of atmospheric oxygen, and are accompanied by a
development of energy which is partly utilised by the cells for
their constructions or organic syntheses. Thus, e.g., the katabolic
action of beer yeast, in the absence of oxygen, breaks up glucose
into alcohol and carbonic acid, with evolution of heat which is
partly employed in the multiplication of the cells of the ferment.
In a well-aerated medium the same beer yeast, on the contrary,
effects complete oxidation of the molecule of glucose, converting it
into water and carbonic acid, and in this case there is a greater
development of heat and a far larger multiplication of Saccliaro-
myces. Pasteur's interpretation of these phenomena is very
illuminating : Saccharomyces, in order to nourish and reproduce
itself, makes great use of the energy developed in the oxidation of
sugar, when it is in an oxygenated medium. When oxygen is
scarce, it utilises the inferior amount of energy which it is able
to develop by abstracting oxygen from the fermentable material,
i.e. from the same sugar, by a kind of internal oxidation.

Accordingly, it is not oxygen as such that is essential to life,
but the energy that is developed by any kind of oxidation. Green
plants have less need of oxygen than animals, because they obtain
from the sun's rays a great part of the energy which they require
in fixing the carbon. If the majority of living beings positively
demand free oxygen, it is because much heat is developed in its
combinations, which can be utilised in a variety of ways.

In proof of the extent to which oxygen is essential to the life

70 PHYSIOLOGY CHAP.

of the various tissues of the higher animals, we may refer to a
remarkable experiment of Pfliiger's on the frog. He placed two
of these animals in an atmosphere at 0° C. which had scrupulously
been deprived of every trace of oxygen. After a quarter of an
hour they exhibited considerable dyspnoea, which, however, was
unaccompanied with convulsions. After five hours the frogs were
quiet and flaccid, but reacted to stimulation with a wire. After
nineteen hours they lay as if dead, and no longer reacted to the
strongest cutaneous stimuli, or showed any trace of respiratory
movement. After twenty hours, they were taken out of their
prison into the fresh air, but no sign of life could be elicited in
spite of repeated insufflation of air through the trachea. On
opening the thorax of one of the frogs, Pfiiiger was astonished
to see the heart still beating with great energy, while the
arteries contained bright red blood. But it was not till two hours
after the animal had been brought into the oxygenated atmo-
sphere that spontaneous muscular movements were exhibited,
followed by reflex movements and spontaneous respiration. The
more complicated voluntary movements, however, which depend
upon the higher nervous system never came back.

To explain this long survival in an atmosphere wholly deprived
of oxygen, it must be admitted for vertebrates also that the living
protoplasm of the various tissues has the property (in different
degrees) of utilising the oxygen which is bound up in the
organic molecules. The cells of the central nervous system
are the most sensitive to deprivation of free oxygen ; other cells,
on the contrary, can live for a long while in a medium destitute of
oxygen, because they have the power of taking it from organic
combinations, and utilising the potential energy.

The most interesting phenomenon, from the point of view of
anaerobic metabolism, is afforded by the group of bacteria which
are not only capable of living in the absence of oxygen, but die
in a medium that contains it, e.g. Tetanus and Anthrax bacilli.
Interesting phenomena, too, are exhibited by other bacteria, e.g.
the comma bacillus of Cholera, which is greedy of oxygen, and is
at the same time capable of living and multiplying enormously
in the intestine, where there is no trace of free oxygen, so that it
must necessarily utilise the combined oxygen of the alkaline salts.

IV. In addition to food -stuffs, water and oxygen, which
penetrate into the body, and directly condition metabolism,
other conditions of a dynamic character are indispensable
in order that the vital functions may be accomplished. The
external temperature exercises a predominant influence on elemen-
tary organisms. Each cell demands a temperature oscillating
between given limits, beyond which the cell must die. For the
majority of plant and animal cells, the maximal limit of endurable
temperature lies between 40° and 47° C. Kiihne found that the

in LIVING MATTER *7l

contractile protoplasm of Amoebae coagulated sometimes at 40° C.,
sometimes at 45° C. For plant cells, Max Schultze found that the
fatal temperature could be raised to 47° C. Other elementary
organisms, indeed, support much higher temperatures, which would
seem incredible if they were not substantiated by direct measure-
ment. In the hot baths of Casamicciola, e.g., certain Algae nourish
at a temperature of 63° C., while, according to Ehrenberg, some
of the ciliated Infusoria (Occillaria or Eotifera) can live at a
temperature of 81° - 85° C. More surprising still, the spores
of Anthrax, according to Koch, Brefeld and others, can support a
temperature of over 100° C., and only lose their vitality completely
after three hours' dry heat at 140° C. It must be remembered in
explanation that the protoplasm of these organisms consists of
proteins combined in such a way that they do not coagulate nor
decompose at these high temperatures.

The minimum temperature compatible with life is equally
surprising. While as a rule the poikilothermic animals and plants
die when the temperature falls to such a point that the water
imbibed by the protoplasm freezes, Raoul Pictet's latest experi-
ments show that a temperature of less than 0° C. is not necessarily
fatal to certain organisms. In fact he ascertained positively that
fishes frozen at a temperature of - 15° C. can recover their vitality,
provided the thawing is effected with great caution. If, however,
the fall in temperature amounts to - 20° C., they inevitably perish.
Frogs, on the contrary, tolerate a temperature of - 28° C., centipedes
one of - 50° C., while, lastly, bacteria can survive exposure to
- 100° C.

Here we reach the vexed question whether frozen animals,
capable of recovering their vitality on thawing, are in a state of
minimal or of absolute latent vitality. Although the latter
possibility is not excluded, Pictet's experiments do not seem to
favour this hypothesis. If these frozen fishes were in a condition
of latent vitality, it is difficult to see why they should not be
indifferent to a fall of temperature below - 15° C., which they can
survive. It seems more rational to admit that at this temperature
metabolic exchanges are still maintained, although reduced to the
lowest terms, and that death ensues when metabolism ceases
altogether.

V. The pressure of the air and water in which these organisms
live must also be considered among the general conditions of life.
It is indeed evident a priori that pressure must act against the
thermal vibrations of the atoms ; when therefore there is a marked
rise of pressure obstructing the thermal vibrations, this favours
the appearance of chemical combinations, while a marked diminu-
tion, by increasing the amplitude of the said vibrations, must
weaken the mutual attraction of the atoms and dissociate the
unstable chemical combinations.

72 PHYSIOLOGY CHAP.

Very little work has been done on the determination of the
limits between which the total pressure of the air and water, and
the partial pressure of the oxygen and carbonic acid which these
contain, condition the life of the organisms which inhabit them.

The experiments of Paul Bert (1873) bring out the interesting
fact that pure oxygen under a pressure of three atmospheres is
fatal to warm-blooded animals, while ordinary air only produces
the same effect at a pressure of 15-20 atmospheres. The same
fatal effect ensues when the partial pressure of the oxygen of the
air is reduced below a certain limit.

In order to determine how great a fall in the barometric
pressure is compatible with life, we may utilise certain data
furnished not so much by ascents of the highest mountains as
from aerostatic ascents, in which the effects of fall of barometric
pressure are not complicated by muscular fatigue. The famous
ascent by Croce-Spinelli, Sivel, and Tissandier in 1875 was fatal
to the two former. When the balloon reached 8000 metres
Tissandier, the sole survivor, lost consciousness, and only came to
his senses when the balloon had dropped to 7059 metres.

We know hardly anything of the effect of aqueous pressures
upon sea animals. Contrary to former conceptions, it has within
the last few decades been ascertained that there exists a special
flora and fauna at the lowest depths of the ocean, in regions where
there is a pressure of several hundred atmospheres, and where no
light can ever penetrate. The fishes caught at the greatest
depths are, when first brought to the surface, so distended in
consequence of the sudden reduction of pressure, which allows the
gases in their bladder to expand, that the viscera protrude from
their mouths and the scales stand up (Keller).

In regard to the pressure exerted by water upon marine
animals, the fact must be insisted on that it exercises a great
influence only upon such organs as, like the fish's swim-bladder,
contain gas in the gaseous state, and do not communicate with the
exterior. The tissues of these animals, which may be considered
as liquids, only feel the effects of the high pressure in a negligible
degree, since, as we know from physics, several hundredths of
atmospheric pressure are necessary in order to obtain any marked
diminution in volume of fluids — these being practically incom-
pressible. This is confirmed by the fact that marine animals, such
as Echinoderms, Molluscs, Crabs, and Selachians or Teleosteans,
which have no swim-bladder, and normally live at a great pelagic
depth, can be transported to the surface without any danger, and
continue to live for a long time in ordinary aquaria when the
pressure of the water is from |-1 metre.

VI. With the exception of those above enumerated, none of
the general external conditions are essential to life. Other
external physical or chemical factors may indeed influence vital

JH LIVING MATTEE 73

metabolism to such a marked degree so as to render them
indispensable to the life of given groups of organisms, e.g. light in
the case of green plants. These special external conditions are
usually known as stimuli, since they exert a direct influence on
the excitability of the protoplasm as expressed in the various
forms of excitation.

In the previous chapter we distinguished between automatic
and reflex excitation ; the former being determined by internal,
the latter by external stimuli. This must not be understood to
mean that the excitations which have the character of spontaneity,
as, opposed to the reflexes provoked from without, are independent
of all external determining factors. The first, like the second, are
effected under the constant influence of the general and normal
external conditions of life ; but while automatic excitations have
for their immediate and determining cause a stimulus or impulse
proceeding from the living matter itself, reflex excitations have
for their immediate and determining cause either a sudden change
in the normal external conditions, or the abrupt and unexpected
intervention of other special external agents.

The external agents that commonly function as stimuli are
represented by different chemical actions, by various mechanical
shocks, by light, heat, and electricity.

The changes in metabolism determined by the action of
stimulating agents may be predominatingly anabolic or katabolic
in character. In the first case there is development of kinetic
energy, and the phenomena are those of- excitation properly so-
called ; in the second, there is an accumulation of potential energy,
and the phenomena are said to be assimilatory. or trophic, or
inhibitory, according to the most conspicuous characteristic which
they present under observation.

When the action of the stimuli is too prolonged, or too frequently
repeated, or exceeds the physiological limits in its intensity,
there may result not an increase but a depression, suspension, or
abolition of metabolism, as exhibited in the phenomena of fatigue,
paralysis, or death of the protoplasm.

We must now briefly summarise the most universal and best
ascertained conclusions in each of these categories of phenomena.

VII. Innumerable chemical compounds function as stimuli
when brought into relation with living matter, i.e. they provoke
phenomena of excitation. The mode in which they act has, how-
ever, been experimentally studied only in a very few cases. We
must therefore confine ourselves to recording certain typical
phenomena which are particularly worthy of attention.

Max Schultze (1863) and Kiihne (1864) made classical re-
searches on the effect of chemical stimuli upon the amoeboid
movements of masses of naked protoplasm, such as the Rhizopoda
(Amoebae, Myxomycetes, Polythalamidae, etc.). The effect most

74

PHYSIOLOGY

CHAP.

generally observed was contraction, i.e. retraction of the pseudo-
podia. The most various chemical substances are capable of
producing this effect : 1-2 per cent solution of sodium chloride,
dilute hydrochloric acid O'l per cent, caustic potash 1 per cent,
weak solutions of other acids, alkalies, or salts.

The Ehizopods treated with these solutions assume a globular
form on retracting their pseudopodia, owing to the concentric
contraction of the protoplasm (Fig. 18). Ciliated cells, on the
contrary, when treated with the same stimuli, increase their
vibratile movements — sometimes to a very marked extent. Smooth
and striated muscles contract, and sometimes exhibit a rhythm of
contraction that they do not normally possess, recalling the
rhythmical movements of the vibratile cilia.

Besides the contractile effects of chemical stimulation, it is

FHJ. is. — Actinosphaerimn Eichhornii. (Venvorn.) a, under normal conditions ; h, at commence^
ment of chemical excitation, the filiform pseudopodia are contracted and varicose ; <;, after
prolonged chemical excitation, the pseudopodia are completely retracted.

possible also to observe expansive effects, i.e. active elongation of
the pseudopodia in Amoebae, Myxomycetes, etc., effects which in the
first instance were studied by Kiihne. On placing an amoeba, for
instance, in a gas chamber in which oxygen has been substituted
for hydrogen, the movements are suspended after a short time.
On again admitting oxygen, the amoebae, after twenty-four hours
of inactivity, at once begin to expand their pseudopodia with
normal vivacity.

Even more important than this direct excitation are the
phenomena of the directive action of chemical stimuli upon the
movements of elementary organisms, phenomena known as chemo-
tactic or chemotropic. Chemotaxis, as first discovered by Engelniann
on Bacteria, observed by Stahl on Myxomycetes, and studied on a
large scale by the botanist Pfeffer in 1887, has assumed a great
importance.

Positive must be distinguished from negative chemotaxis. The

in

LIVING MATTER

former consists in the active approach of the micro-organisms to
the source of the chemical stimulus, as if attracted by it ; the
second consists in the opposite phenom-
enon, i.e. active withdrawal from the seat
of the stimulus, as if it exerted some
repulsive action.

A given solution may be an energetic
chemotactic stimulus for one organism,
and weak 'for another. The efficiency of
the stimulus depends on its chemical
constitution ; potash, e.g., is active in
combination with one acid and not with
another. Certain poisons (sodium salicyl-
ate, morphia) in weak solutions exert an
attractive action, in concentrated forms
a repulsive action. Some substances
(alcohol, alkalies, free acids) always have
a repellent action, i.e. they exert negative
chemotaxis.

The method adopted by Pfeffer in
studying chemotaxis is very simple : he
merely immerses in the water which con-
tains the microbes a capillary glass tube
filled with the solution to be investigated,
and closed at one end. If the microbes
penetrate into the tube, there is positive
chemotaxis ; if they move away, there is
negative chemotaxis. If, e.g., a O'Oo per
cent solution of malic acid is introduced
into the capillary tube, the open end of
which dips into a drop of fluid containing
the spermatozoids of Ferns, the malic acid
will scarcely have begun to diffuse in the
drop when the spermatozoids move towards
the entrance of the tube and crowd into
it. The same thing may be seen with a
much weaker solution (O'OOl per cent) of
malic acid. The movements of the sper-
matozoids must be directed by the differ-
ence in concentration of the acid which
is in contact with the different parts of
their body. When the concentration of
the acid diffused in the drop becomes the
same at every point, it can no longer

exercise any directive action upon the movements of the sper-
matozoids.

Leber, Massart and Bordet, Metschnikoff and others discovered

FIG. 19. — Positive cliemotaxis of
leucocytes in presence of Maphy-
lococcu&pyogenes allius. (Massart. )
Capillary glass tube (magnified
under the microscope), closed
at one end, and tilled with a
culture of Staphylococcus, to-
wards which the leucocytes
are streaming through the open
end of the tube. The observa-
tion is made after the capil-
lary tube has been introduced
into the peritoneal cavity of
the frog, or beneath the skin of
a rabbit, and kept there 10-12
hours.

76 PHYSIOLOGY CHAP.

chemotactic activity in the leucocytes of vertebrate blood. The
products of the metabolism of pathogenic bacteria exert a marked
•chemotactic action upon them (Fig. 19), a fact which is of great
importance in the interpretation of the inflammatory phenomena
of infective diseases, as we shall see in discussing Blood.

VIII. Mechanical stimuli (blow, contact, puncture, shake,
pressure, etc.) are the simplest means of provoking excitation
in living matter. The least shake of the object-carrier on which
the movements of an amoeba are being watched under the
microscope is sufficient to produce temporary standstill, and if the
impact is strong enough a partial retraction of the pseudopodia.
If the shock is repeated at frequent intervals the effects induced
by each stimulus summate, resulting after a minute or two in a
true mechanical tetanus, during which there is a concentric
•contraction of the whole of the protoplasm, which causes the
amoeba to assume a globular form.

In addition to general mechanical stimulation, the effects of local
stimulation have been experimentally studied, by touching or stab-
bing the amoeba with a blunt body or with very fine needles. In this
case, when a reaction appears, it is at first confined to the point
stimulated, whence it is slowly transmitted to the rest of the body.

The mechanical excitations of the living matter consist
for the most part in a modification of the pressure relations
under which it exists. In every case in which there is a
difference of pressure at two different parts of the body of any
organism, phenomena of excitation are manifested, which, since
they are produced by a unilateral pressure, are known as barotactic.
Several forms of barotaxis may be distinguished according to the
kind of pressure, while it also can be positive or negative, according
-as the organism turns towards the side of greater or less pressure.

Verworn groups under the name of thigmotaxis the tendencies
exhibited by many organisms, both animal and vegetable, to
adhere to the surface of more solid bodies, or to penetrate through
their pores, even in defiance of gravity.

Stahl defines as rheotaxis the peculiarity certain organisms
exhibit of moving in the direction contrary to a current of water.
Since this movement is determined by pressure acting in a particular
way, rheotaxis is merely a special form of positive barotaxis.
Thus far the phenomenon has been studied only in the plasmodia
of Myxomycetes and in a few plants ; but it is highly probable that
the rise of the spermatozoa in animals and man from the vagina
to the uterus, and thence to the oviduct to meet the ovum, is a
rheotactic phenomenon, since this movement is accomplished in a
direction contrary to that of the current of mucous fluid set up by
the cilia of the epithelial cells which line the surface of the uterus,
and which vibrate in a direction contrary to the movements of the
spermatozoa.

Ill

LIVING MATTER

A third form of barotaxis is geotaxis, or the well-known
property of plants to place themselves with their median axis in a
definite direction toward the centre of the earth. The stimulus in
this case is afforded by minimal differences of pressure acting on
points at different heights of the organism. The stems of trees
grow away from the centre of the earth, and are, therefore,
negatively geotactic; the roots grow toward the centre of the
earth, and are, therefore, positively geotactic ; further, the leaves,
and not seldom the branches, grow in a direction tangential to the
earth's surface, and thus exhibit transverse geotaxis.

. Loeb (1888) discovered that geotaxis is a phenomenon widely
diffused among animals also. It is possible to convert animals
that exhibit negative, into animals ex-
hibiting positive, geotaxis, and vice versa.

Many infusoria and bacteria exhibit
geotactic phenomena. They frequently
collect on the surface of the water in
which they live (negative geotaxis, Fig.
20) ; at other times they sink down and
crowd together at the bottom (positive
geotaxis).

Knight (1809) showed that geotactic
phenomena are determined by differences
in pressure acting like gravity on the
different points of the vegetable organ-
ism. He employed wheels turning in
a vertical plane, to which he attached
plants in various positions, as well as
germinating seeds. He found that all
the stems grew in towards the centre
of the wheel, while the roots grew away
from it. Jensen practically repeated the
same experiments on infusoria living at the surface of the water,
by rotating the test tubes which contained them in the centrifuge.
Provided this were not driven too quickly, so as to make the
infusoria, which are specifically heavier bodies, drop to the bottom
of the test tube, they remained at the top, where pressure is lowest
during rotation.

IX. Heat rarely exerts any direct stimulating action on living
matter. In the higher animals, however, the special terminal
organs of certain centripetal nerve-fibres are excited by heat.
Kuhne was the first to observe thermal tetanus in Amoebae
when the temperature was raised to 35° C. On cooling the
atmosphere again, the amoeboid movements were slowly restored ;
heating to 40-45° C. kills the animal by coagulation of its proto-
plasm.

When the heat acts on one part only of the amoeba, the

FIG. 20. — Glass tube containing Para-
moecia. (Jensen.) In consequence
of negative geotaxis, the infusoria
have collected at the top of the
tube, although they are specifically
heavier than the fluid.

78 PHYSIOLOGY CHAP.

stimulus is found capable not merely of exciting protoplasmic
movements, but even of determining their direction up to a certain
point. Verworn observed that amoebae always move in a direction
opposite to the thermal stimulus, i.e. they exhibit negative
thermotaxis. Mendelssohn studied on a ciliated infusorium//
Paramoecium, the thermotactic influence of different grades of
temperature. When one end of a vessel full of liquid, and
swarming with Paramoecia, is heated to 24-28° C., the creatures
move to the cooler end of the vessel ; when, on the contrary, one
end of the vessel is cooled below the said degrees, the infusoria
move towards the warmer end. Thus there may be positive or
negative thermotaxis according to the degree of temperature.

In this case, as in cherno- and barotaxis, the movement are
determined by the difference of temperature at the two poles of
the Paramoecium, differences which can be estimated at about
0-01° C.

X. Light rays, like heat rays, act as a direct stimulus on
comparatively few elementary organisms. In the higher animals
they only affect the nervous elements of the retina, and great
intensity is required to stimulate the cutaneous -endings of the
thermal nerves as well. The skin of invertebrates is also excitable
to light.

Many observations have been made in order to determine the
nature of the action of light upon Protista, and to ascertain
whether excitability to light is a general property of protoplasm,
or first appears during the phylogenic evolution of living beings.
The results with amoebae were purely negative. Other Khizopoda,
however, were seen to contract on sudden illumination.

E. Oehl (1886-91) saw that the leucocytes of the blood both of
man and frog, when exposed to bright sunshine under the
microscope, reacted by active migratory and amoeboid movements,
which were not present previous to the photic stimulation.

The work of Strasburger and others shows that intensity of
light exerts a great influence on bacteria and diatoms, so that up
to a certain point of intensity they exhibit positive phototaxis,
and approach the source of light ; with greater intensity they
move farther off, and exhibit negative phototaxis ; at a mid-point
they show themselves wholly indifferent. The wave-length of the
light rays is also of great importance. Engelmann has shown
that the Bacterium photometricum (observed in the micro-
spectroscope) swarms into the region of the ultra-red rays, and to
a less extent into that of the orange and yellow rays, i.e. towards
Frauenhofer's D-line (Fig. 21).

The term heliotaxis has long been employed to denote the
common property of plants to turn on their axis in the direction
-of the sun's rays. The phenomenon is particularly conspicuous
in plants grown inside the house. Both stems and petioles curve

Ill

LIVING MATTEE

towards the light that conies in at the windows (positive heliotaxis),
while the surfaces of the leaves spread out perpendicularly in the
direction of the light rays (transverse heliotaxis). In plants with
aerial roots these turn and grow towards the darkest part of the
room (negative heliotaxis).

FIG. 21. — Bacterium photometrii'iim, in micro-spectroscope. (Engehnanii.) The bacteria
are collected in the region of the ultra-red and yellow rays.

Heliotactic movements are especially favoured by the blue and
violet rays ; red and yellow rays are practically inactive (Fig. 22).

Loeb (1888) described phenomena of heliotaxis in many
animals, which are perfectly comparable with those observed on
plants ; they are also determined by the most refrangible rays of
the spectrum. The mechanical explanation of the phenomenon is,
according to Loeb, that the symmetrical points of an organism

FIG. 22. — (lalium, aparina showing heliotaxis. (Noll.) The plant curves left or light, to the
source of light, as indicated by the arrow L. The leaves exhibit transverse heliotaxis.

possess equal excitability, and the unsynimetrical points unequal
excitability ; the points nearest the buccal pole possess an excit-
ability greater than, or different in form from, that of the points
nearest the opposite pole. By this is meant that with unilateral
illumination the muscles of the excited side are thrown into a
tension which is relatively greater or less than that of the muscles
of the opposite side, so that the animal deviates in the direction of
its movements, in the sense of positive or negative heliotaxis. In

80 PHYSIOLOGY CHAP.

some animals it is possible to transform positive into negative
heliotaxis, and vice versa.

XL Electrical stimuli are those most frequently adopted by
physiologists for the excitation of living matter. Their action on
muscle and nerve will be treated at length in another connection.
Here we must confine ourselves to the effects of electrical excitation
on unicellular organisms.

Kiihne and Engelmann were the first who investigated this
subject. They both found that after weak induction shocks the
amoebae suspended their locomotor movements; with stronger
shocks the pseudopodia assume a globular form ; if the shocks were
still further strengthened, electrical tetanus resulted, followed by
a kind of coagulation of the protoplasm, which was shared by the
nucleus. Galvanic currents also, in proportion with their intensity,

FIG. '23. — Kathodic galvanotaxis in a drop of water with paramoecia. (Verworn.) c, on closure
of current, the paramoecia swim in curved lines to approach the kathode ; l>, paramoecia
collected round the kathode.

produced a partial or total contraction of the protoplasm of
amoebae.

Verworn discovered a directive action of the galvanic current
analogous to that produced by other stimuli, which he terms
galvanotaxis. He particularly investigated certain species of
ciliated infusoria, e.g. Paramoecia. When immersed in a drop of
water through whicli current is passing, these infusoria flock to
the kathode in wavy movements which are more pronounced in
proportion as the current is weaker. On breaking the circuit the
Paramoecia scatter themselves again uniformly through the drop
of water (Fig. 23). This is not a case of kataphoric action, i.e. of
mechanical transport in the direction of the current, such as might
occur with non-living particles, because the infusoria would then
swim in a straight line, and move more rapidly, with no orientation
of the principal axis of the body. Moreover, chloroform or ether
paralyse these movements, which would not occur if they did not
represent physiological phenomena in living beings. Budgett and
Loeb noted that these same Paramoecia moved to the anode if the
water which contains them is replaced by a 0*4-0*7 per cent
solution of sodium chloride.

in LIVING MATTER 81

Dineur found that the leucocytes of the blood also exhibit
galvanotactic properties with a marked preference for the anode.

A different form of kathodic and anodic galvanotaxis was
observed at the end of 1885 by Hermann. When a galvanic
current is passed through a vessel containing tadpoles or fish
embryos, these animalcules orientate themselves with' their long
axes in the direction of the lines of current so that the head faces
the anode and the tail the kathode. They remain in this
position as long as current is passing ; if its direction be reversed,
they face to the opposite direction, like soldiers at the word of
command.

Verworn recognised another form of galvanotaxis in a ciliated
infusorium, Spirostomum amliguum, which, when traversed by the
galvanic current, turns so that the principal axis of its body is
at right angles to the direction of the current. This he terms
transverse galvanotaxis.

XII. The directive action of stimuli, particularly of those due
to light and temperature, is of special importance for marine
organisms. Scientific data in regard to the fauna and flora of the
ocean are at present scanty in comparison with our knowledge of
the terrestrial fauna and flora, but there seems reason to believe
that the variety and magnitude of the animal and vegetable
kingdoms of the ocean are incomparably greater than of those
upon the earth. The paucity of data in regard to life in the deep
sea is obviously due to the difficulty of securing such beings as
live at a depth of several thousand metres below the surface.

Many expeditions have been organised for the purpose of
studying marine biology; these are equipped with ponderous
dredges, and are intended to remain several months at sea in order
to collect with different kinds of apparatus, at various seasons of
the year, the organisms that exist at different levels or at the
bottom of the ocean. The most important have been the Challenger
Expedition, conducted by Murray and Thompson (1884), and the
Valdivia, conducted by Chun (1898-99), in different seas. In the
Mediterranean, Krupp, on the Maia and the Puritan, investigated
the pelagic fishes, the scientific results of this expedition having
been illustrated and published by S. Lo Bianco (1901-3).

The distribution of organisms in the different strata of water
(bathymetric distribution, either in the vertical or the horizontal
direction) has been determined with a fair amount of accuracy
by the use of special contrivances, constructed ad hoc. Such
are the nets fitted with an apparatus enabling them to be closed
at any required depth (measured by the soundings), so that they
cannot, when pulled up through the supernatant strata of water,
enclose any animals from these higher levels. Some are draw-nets
weighted with heavy rings of iron or other metal, which fall to the
bottom and are pushed along, gathering up the living organisms

VOL. I G

82 PHYSIOLOGY CHAP.

from the ocean bed. By this method a certain amount of exact
knowledge has been obtained in regard to the fauna and flora of
the seas. As regards the vertical distribution of these pelagic
organisms, it is interesting to note that the forms which live at
different heights in the same region of the sea vary enormously
among themselves, so that we ought to speak of so many special
biological zones in relation to the different depths of water.

The main factor which determines this diversity in the forms
of life at various depths, is light ; then come temperature, and
movement of the water, which are of secondary importance ; while
pressure of water is, save for the Teleosteans provided with a swim-
bladder, of no importance, as we have already pointed out.

In regard to light, the following zones can be distinguished
in a vertical section of the water of the ocean : —

(a) A first zone, highly illuminated, which extends from the
surface to about 30 metres down.

(ft) The shaded zone, from about 30 metres below the surface
to the farthest limits to which light penetrates (some 500 metres
deep).

(c) The dark zone, which commences at 500 metres, and extends
to the greatest depth known to be inhabited, i.e. some thousands
of metres (in the Mediterranean the Puritan dredged to a depth
of some 1500 metres).

It agrees with this, and with the fact that light is an indis-
pensable condition of plant life (chlorophyll function), that no
vegetable organisms (algae) have so far been dredged at a lower
level than the shaded zone, i.e. below 500 metres. On the other
hand, numerous animal organisms have been found, and described,
below this level, in accordance with the fact that light is not
an indispensable vital condition to animals. It is, however,
interesting in those animals which live entirely in the dark, to
observe the morphological changes in the sense organs destined
to receive luminous stimuli (eyes). In some they atrophy com-
pletely, as in terrestrial creatures living in caves; in others, on
the contrary, they develop enormously ; while in order to furnish
the stimuli required to make them perform their functions, they
develop numerous and powerful luminous organs in different parts
of the body.

Hensen was the first to propose the collective name of Plankton
(ir\avKTo<s, wandering), which is now universally accepted, to indicate
the world of living organisms (fauna and flora) in mid-ocean ;
while the name of Benthos (ftcvOos, bottom) is applied to the
aquatic organisms that live at the bottom of the sea.

Lo Bianco (1903), on the strength of the facts already discussed,
to the effect that light is the factor determining the varying dis-
tribution of plankton, proposed to term the biological stratum
which corresponds with the first of the above zones phao-plankton,

in LIVING MATTER 83

the organisms living in the second, shaded zone, kneplio -plankton,
and those living in the third, dark zone, scoto-plankton.

Since, beside these, there are many organisms which live in-
differently on the surface or at the greatest depths, he proposes to
collect the four classes together under the collective name of panic-
plankton.

This is not the place in which to enumerate the forms and
species of the organisms that constitute, respectively, these four
great classes of marine life. We will only state that phao-plankton
consists principally of ova that find in this zone the best con-
dition for their evolution, and of the larvae or young forms of
organisms, which in the adult state live either at the bottom
(benthonic forms) or in the deeper strata of the sea. Besides the
phao-plankton, certain species of Crustacea (copepods) are abundant
The temperature of the water in this zone oscillates from 13° C. in
winter to 26° C. in summer. The more or less copious contents of
the phao-plankton varies with the seasons ; it is particularly
abundant in the spring because reproduction is most active at that
season. A striking characteristic of most components of phao-
plankton is their minute dimensions. It is a remarkable fact that
many pelagic forms are larger in proportion with the depths at
which they live.

The temperature of the second (shaded) zone varies from 13° to
24° C. in its superficial stratum, and by a couple of degrees only in the
deeper parts, becoming constant (13° C. in the Mediterranean) below
that. The plankton which inhabits this region (kneplio -planktoii)
is the richest of all. " This zone," writes Lo Bianco, " since it is
sheltered from the direct rays of the sun and movements of the
waves, is the habitat most favourable to pelagic organisms ; these
physical conditions make it the richest and most varied in both
plant and animal forms."

Many varieties of scoto-plankton are brilliant in colour, e.g.
most kinds of Crustacea have very red bodies.

XIII. After discussing the general conditions and external
stimuli of cell life, we ought, in another chapter, to consider the
general conditions and internal stimuli, i.e. such as arise within
the organism itself, and which govern all the vital phenomena that
appear to be spontaneous or automatic — whether these originate
in predominatingly katabolic processes (protoplasmic movements,
sensory phenomena, development of heat, electricity, and light), or
are due to predominatingly anabolic processes (phenomena of
nutrition, reproduction, evolution). Our concrete knowledge of
these internal conditions and stimuli is, however, at present so
fragmentary that a few paragraphs will contain such general
notions as have been determined in relation to them.

The constitution of a complete elementary organism, capable,
i.e., of every kind of essential vital activity, requires that the

84 PHYSIOLOGY CHAP.

protoplasm shall have attained a certain degree of organisation
whether chemico-physical or morphological, so as not to be homo-
geneous in any individual particle. We saw in Chapter I.
that the minimal degree of organisation necessary to constitute
a complete organism is in all probability represented by its
differentiation into cytoplasm and nucleus. A homogeneous bit
of living matter detached from an elementary organism, either of
cytoplasm or of nucleus, is incapable of prolonged existence ; on
the other hand, a minute particle of heterogeneous protoplasm, i.e.
a fragment of nucleus and cytoplasm combined (p. 13), is capable
of nutrition, integration, and reproduction. Vital metabolism
cannot continue without the natural union of these two essential
parts of the cell, showing that there exist between them reciprocal
exchanges of matter and energy — the universal internal condition
of cell life.

The same applies to complex or multicellular organisms. In
the lowest grades of organisation, it is possible to divide a multi-
cellular individual into one or more segments without fear of
killing it ; each segment continues to live, to show signs of
sensibility, to grow and regenerate into a new individual like that
of which it was originally a part. The classical example of this
marvellous phenomenon was given for the first time on animals,
in 1774, by the Genevese naturalist Trenibley, with fresh-water
polyps. The interpretation now accepted is that the cells of which
the polyp is built up are not too highly differentiated in structure
and function to be capable of mutual substitution ; each cell, i.e.,
represents the germ of the entire polyp, and can therefore recon-
struct it.

In the higher grades of organisation, on the contrary, where
there is a more or less advanced differentiation, both morphological
and functional, of the parts that constitute the organism as a
whole, it is no longer possible to multiply the individual by
sections, because the life of each part is conditioned by that of the
others, and they all represent integrating factors of more or less
importance to the life of the aggregate. In the higher vertebrates
also it is possible to amputate a limb or an organ, or even several
limbs or organs, without necessarily causing death. This is either
because the function of the lost parts can be replaced by others, or
because there is not between the missing parts and those which
remain a reciprocal exchange of matter and energy sufficient to
make them indispensable to the life of the entire aggregate, in the
way that the nucleus is necessary to the life of the cytoplasm
and the cytoplasm to the life of the nucleus.

We know nothing positive in regard to the conditions, the
internal stumuli, and the intimate mechanism of the phenomena
of the nutrition and growth of protoplasm, and of cellular repro-
duction or neo- formation. All our ideas on this subject are

in LIVING MATTEK 85

exclusively morphological and are treated at length in text-books
of histology, to which the reader should refer.

Very undetermined also, and far from concrete, is our know-
ledge of the internal conditions and stimuli of all those vital acts
of which protoplasm, is capable, even when it is as far as possible
protected from every external agent that can function as a
stimulus, by deviating from the general external conditions.

Some hold that the stimulus to movement and other auto-
matic acts arises in the waste products that develop and accumu-
late in the cell, in consequence of its metabolism. In this case
it is evident that both automatic excitations and reflexes are
the effect of stimuli extrinsic to the protoplasm ; but in the former
these are generated by the activity of the organism itself, in the
latter they come from without.

The intrinsic fallacy of this doctrine is easily appreciated when
we consider that, on its showing, all the phenomena of excitation,
paralysis, or of fatigue that are seen in the different forms of auto-
intoxication must be regarded as automatic phenomena, because
the agents by which they are determined (e.g. carbonic acid,
as in asphyxia from suffocation, urinary products, as in uraemia,
muscular toxins, as in fatigue or exhaustion consequent on exces-
sive and prolonged muscular exertion) all originate in the meta-
bolic activity of the different tissues of the body.

The true concept of automaticity is very different : either we
must demonstrate that there are no automatic phenomena, properly
speaking, or we must hold that the stimulus, or, more generically,
the determining cause of the phenomena, is intrinsic to the
elementary organism which exhibits them, and consists in an oscil-
lation (rhythmical or irregular) of its metabolism or its excitability,
by which it finds within itself the conditions for the development
of the energy it has stored up (Luciani, 1873). The chemical and
molecular transmutations of protoplasmic metabolism are usually
conceived as something continuous and monotonous, which can
only be changed or modified by external influences ; but nothing
forbids us to imagine a more vital process, which without invoking
external factors may become disturbed of itself, or in consequence
of the particular structure of the protoplasm, or the facility with
which the particles of which it is composed are able to change their
relations.

XIV. Various hypotheses and theories have been put forward
as to the nature of the intimate processes that go on in living
matter, and by which the several vital phenomena, thus briefly
summarised, are determined. The starting-point and fundamental
concept from which these different speculations have for the most
part been evolved is invariably the same, starting from the oft-
accentuated hypothesis that chemical energy is to be regarded as
the sole and ultimate cause of all the manifestations exhibited by

86 PHYSIOLOGY CHAP.

living organisms — which chemical energy, introduced into the
animal body in the potential form by the different complex food-
stuffs, becomes free or kinetic, owing to the activity of the living
protoplasm.

From this it may be deduced that the living organism is
distinguished from the dead in virtue of the incessant metabolism,
or exchange of materials, which is taking place, even when it is
apparently in the state of most complete repose. These material
exchanges are, of course, associated with exchanges of energy.

Pfliiger, in his classical essay on Physiological Combustion in
Living Organisms (Pfliiger s Arch. x. 1875), recognised on the
strength of many different experimental data that the essential
characteristic of living matter consists in its being highly un-
stable, splitting up and regenerating itself incessantly.

" The fact," he writes, " which every biologist encounters on all
sides, is the amazing instability (Zersetzbarkeif) of almost all living
matter. . . . This instability is the cause of excitability. Does
not the infinitesimal vital force of a ray of light evoke the most
potent effects in brain and retina ? I think no one will deny that
living matter is not merely highly unstable (zersetzbqf), but also
that it is continually breaking up (zersetzend)" The ultimate
cause of these chemical transmutations, and of the continuous
atomic and molecular transformations of living matter, lies in the
intra-molecular heat which comes into play in virtue of the specific
nature of living matter.

In summing up his theory Pfliiger concludes : " The vital
process is the intra-molecular heat of the highly unstable
(zersetzbarer) molecules of protein present in the cell -substance,
which split up (zersetzender) by dissociation — with formation of
carbonic acid, water, and starch compounds — and which, on the
other hand, are perpetually regenerated, and also increase by
polymerisation."

We saw in the last chapter that Metabolism may be regarded
as the result of two opposite antagonistic processes: the ana-
bolic, synthetic, restorative process, and the katabolic, analytic,
disintegrative process. E. Hering (1888) gave to the former the
name of Assimilation, to the latter that of Dissimilation, and laid
down certain important considerations in regard to the theory of
the intimate processes of living matter.

He starts from the indisputable fact that living matter at any
given moment is the seat of two opposite processes which arise and
proceed simultaneously, even when no external stimulus is acting
on the living matter. He gave the name of autonomous assimila-
tion (A) and autonomous dissimilation (D) to those processes
which take place in living matter, when no external stimulus
intervenes. If these two opposite processes are equal, so that
neither the one nor the other predominates, then the substance

in LIVING MATTEE 87

alters neither quantitatively nor qualitatively ; we have what
Hering terms autonomous equilibrium.

But, as we have seen, external stimuli are continually acting
upon living matter and modifying the state of its metabolism.
Hering distinguishes two kinds of stimuli, which differ essentially
inter se, inasmuch as the one kind excite the dissimilatory phase
(dissimilatory stimuli) — and these are more usually noticed —
while the other kind act by exciting or augmenting the phase of
assimilation (assimilatory stimuli).

Assuming, then, the action of a dissimilatory stimulus,
dissimilation will be increased, and is termed by Hering allono-
mous dissimilation : the living substance changes in its quality
and quantity, and has a lower energy value (is "below par").
Hering assumes that in proportion as the living matter, under
the influence of this stimulus, is excited to increased dissimila-
tion, its inherent tendency to the dissimilatory phase diminishes
while its inherent tendency to the assimilatory phase increases.
Owing to this property, which he terms the internal automatic
regulation of living matter, at the close of the dissimilatory
stimulus the opposite process of assimilation sets in more
vigorously than usual, so that after a certain time the living
matter regains the mean energy value of equilibrium (i.e. is " at
par " ) towards which it strives — the more incessantly, and with
so much the greater energy, the farther it is removed from the
said equilibrium in the one direction or the other, by the action of
external stimuli.

It may, however, happen that the dissimilatory stimulus does
not cease, but persists for an indefinite time ; then in consequence
of the diminished dissimilatory activity, and the simultaneous
increase in autonomous assimilation, a new state of equilibrium is
finally arrived at, which Hering terms allonomous equilibrium,
and which prevails so long as the dissimilatory stimulus is acting.
The living matter has adapted itself to the prolonged action of the
stimulus.

The same reasoning holds for the action of the assimilatory
stimuli, which provoke an increase in the assimilatory process.

Verworn, in his General Physiology (1895), has developed
Hering's doctrine, while he takes Pfiiiger's theory also into
consideration.

" Pfliiger's assumption of living protein, which distinguishes
living cell-substances from dead, and in the loose constitution of
which lies the essence of life, is necessitated. But this substance
must be of essentially different composition from dead protein,
although, as follows from the character of its decomposition-
products, certain characteristic atomic groups of the proteins
are contained in it. The great lability that distinguishes it
from other proteins, can be conditioned only by an essentially

88 PHYSIOLOGY CHAP.

different constitution. In order to distinguish this body, there-
fore, from dead protein, and to indicate its high significance in
the occurrence of vital phenomena, it appears fitting to replace
the term ' living protein ' with that of biogen. The expressions
'plasma molecule/ 'plasson molecule/ 'plastidule/ etc., whiah
Elsberg and Haeckel have employed, and the conceptions of
which are comprised approximately in the expression 'biogen
molecule/ are less fitting in so far as they easily give the
impression that protoplasm is a chemically unitary body, which
consists of wholly similar molecules; such a view must be ex-
pressly rejected. Protoplasm is a morphological, not a chemical
conception."

Verworn gives the name of Biotonus to the ratio between the
assimilatory and dissimilatory processes, which Hering, as we have
seen, regards as the theoretical foundation of the processes that go
on in living matter.

" If we consider," he goes on, " the quantitative relation of
assimilation to dissimilation in a considerable mass of living
substance, such, for example, as is contained in a cell, we find it
very variable, and even without the influence of stimuli it changes
within wide limits. This relation of the two processes in the unit

of time, which can be expressed by the fraction ^ and will be

termed, in brief, biotonus, is of fundamental importance for the
various phenomena of life. The variations in the value of the
fraction effect all changes in the vital manifestations of every
organism.

" The fraction ^- is merely a general form of the expression

of biotonus. In reality, assimilation and dissimilation are not
simple processes ; on the contrary, the events that lead to the
construction of the biogen molecule, and the formation of the
decomposition-products, are very complex and consist of processes
closely interwoven. Hence if we would express biotonus in a
specialised way, we must give the fraction the form

in which a, av a.2, a3, etc., and d, dv d2, ds, etc., represent the
partial processes that combine to form the whole."

With our present limited knowledge of the more special
transformations that take place in living substance, it is impossible
approximately to gauge the significance of the individual com-
ponents of the .biotonous quotient. Verworn, therefore, refers

only to considerations arising from the general formula g.

Where assimilation and dissimilation are equal in the unit of

in LIVING MATTEE 89

time, the fraction g = 1, Bering's metabolic equilibrium. In this

state, the sum of the excreted substances of every kind is equal to
the sum of the ingested substances.

" If the individual members of series A increase in a constant
relation to one another, while the members of series D remain
equal or decrease, so that in the unit of time the sum of the
members of A is greater than that of the members of D, then the

metabolic quotient ^>1-

" This case is realised in growth, where the formation of living
substance surpasses its destruction.

" If, vice versa, the members of series D grow proportionately to
one another, while those of series A remain unchanged, or become

smaller, biotonus *f>1- This condition is the basis of atrophy,

and leads finally to death."

In a later work (1903) Verworn developed this theory more
fully, giving it the name of Biogen hypothesis and enumerating
the various indirect arguments, of early or recent date, which tell
in its favour, and show how by its application we may arrive at a
unitary explanation of the action of the several stimuli upon
living matter.

"In my opinion" (he concludes) "the principal value of the
biogen hypothesis lies in the fact that it enables us to gather up
all the vital phenomena under .a single, very definite and simple
point of view, without contradicting any of the facts hitherto noted.
This hypothesis provides us with a clear idea of the phenomena
fundamental to the whole of life, and is thus of singular utility
in facilitating the interpretation of many complex and controverted
problems."

" Still " (he adds) " it must once more be pointed out that this
is merely a working hypothesis, and that it would be quite
fallacious to attribute to it any other value. Whether it be a
faithful representation of the real facts, or whether it be in-
adequate, matters little ; as a working hypothesis it keeps its
value so long as it is useful and fecund in the progress of science.
The history of science is richer in fallacies than in truth ; but in
the development of the human mind a fertile error is of infinitely
greater value than a sterile fact."

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P. B. HADLEY. Galvanotaxis in Larvae of the American Lobster Homarus

americanus. Amer. Journ. of Physiol., 1907, xix. 39.
J. R. MILLER. Galvanotropismus in the Crayfish. Journ. of Physiol., 1906-7,

xxxv. 215.

CHAPTER IV

THE BLOOD : FORMED CONSTITUENTS

SUMMARY. — 1. Arrangement of human physiology, and classification of
functions. 2. Importance of the blood as centre of the vegetative system
and agent of general metabolism. 3. Historical development of haematology.
4. General physico-chemical characters of the blood. 5. Estimation of total
quantity. 6. Physical and morphological characters of erythrocytes, and
estimation of their relative quantity. 7. Chemical composition. Properties of
haemoglobin and its derivatives. 8. Character, composition, and physiological
properties of leucocytes. 9. Blood platelets, and elementary granulation of the
blood. Bibliography.

JUST as no absolute difference can be admitted between the vital
activities of plants and animals, so no absolute difference can be
recognised between the functions of the individual living cells,
tissues, organs, and systems of which the higher organisms,
including man, consist. It is nevertheless to be observed that in
all complex organisms, whether animals or plants, there is pari
passu with the morphological differentiation of the primitive cell,
which occurs during ontogenic development, a functional differ-
entiation, resulting in a division of labour, i.e. in the greater
or less specialisation of the capacities or functions of the different
parts. As in the great industries an ever-increasing development
and perfection of industrial products is obtained with the pro-
gressive division of the work assigned to the various groups of
workmen, so the increasing perfection observed in the scale of
living beings is essentially the result of progressive morphological
differentiation and functional specialisation in the cells of which
the organism is composed (Milne Edwards, 1827). It is evident
that the arrangement of the special physiology of man, and
the rational classification of his functions, must rest upon this
specialisation of the different organs and systems in the higher
animals.

I. At the commencement of the nineteenth century Xavier
Bichat, in his inspired book Sur la vie et la mort, made a sharp
distinction between two orders of functions in the higher
organisms, which he designated as the functiqns of organic (or
vegetative) life and the functions of animal life respectively.

91

92 PHYSIOLOGY CHAP.

By means of the former, says Bichat in effect, these organisms are
constantly transforming into their own substance the materials
which they receive from outside, while they continually eliminate
the useless products of consumption ; by means of the latter, they
feel and perceive the external world, express their sensations,
perform voluntary movements under the influence of these, and
are able to express their desires and fears, their pains and
pleasures.

Although modern science has established the unitary con-
ception of life, and has refuted the supposed antagonism between
the functions of plants and of animals, Bichat's general distinction
holds good as the basis of a rational classification. It is a fact
that the cardinal function of plants, taken as a whole, is the
synthetic building-up of organic matter, while that of animals is
its disintegration.

On the other hand, it is undeniable that the higher animals
possess a system of organs and apparatus which essentially serve
the internal life of the body, by preparing and constantly re-
newing the pabulum common to all the living elements of which
it consists : while there is a second system which especially serves
the external life, by developing the potential energy of the living
matter. The first system recalls the predominance of anabolism
in plants, as compared with animals ; the second the predominance
of katabolism in animals, as compared with plants.

Yet, if we attempt to determine exactly which organs and
apparatus compose the vegetative system, in distinction to those
of which the animal system consists, we encounter difficulties.
The embryological criterion, so often invoked in this connection,
i.e. the derivation of the different parts from one or other of the
three germinal layers, leads to no satisfactory result, since it is
now well established that tissues and organs are developed from the
external, and yet more from the middle, layer, which obviously
belong some to one system and some to the other. Clearly these
two systems do not represent two distinct and superposed organisms,
but rather two that are intimately connected and interdependent,
to be distinguished only by artificial means, contingent to a certain
extent on individual judgment and appreciation.

It is the obvious function of the vegetative system, as a whole,
to keep constant the quantity and quality of the mass of blood,
from which is formed the lymph or plasma constituting the
common internal medium indispensable to the life of each vital
element. This system consists necessarily of the blood, of the
cardio- vascular apparatus by means of which it circulates, and of
the whole of the glandular organs and apparatus designed for its
constant renewal, elaboration, and cleansing.

On the other hand, the function of the animal system is to
bring the animal through its sense organs into relation with the

iv THE BLOOD: FOKMED CONSTITUENTS 93

external world, and to modify these relations in various ways by
means of the organs of motion. It consists accordingly of the
central and peripheral nervous system, i.e. the sensory and
conducting organs, and of the muscular and skeletal system, i.e.
the active and passive apparatus of movement.

The blood is the centre and objective of all the functions of
the vegetative system ; the brain is the central seat and focus of
the functions of the animal system.

A third order of physiological processes must further be dis-
tinguished from the special functions of the vegetative and animal
systems, in which both these and, in a certain sense, the entire
organism participate. These are the physiological phenomena
of general metabolism and the regulation of the balance of output
and intake ; thermogenesis and the regulation of the heat balance \.
sexual and reproductive functions ; the physiology of the embryo,
and of the different stages of uterine life.

II. As centre of the vegetative system, the blood contains all
the histogenic substances destined to nourish and renew the
tissues, and all the histolytic products of consumption, useless or
noxious residues, to be eliminated. The first, which filter through
the living walls of the capillaries, pass in the form of lymph into
the interstitial plasma-spaces of the tissues for which they provide
aliment; the second, secreted by the tissue cells, pass into the
blood by way of the lymph vessels, and are thence eliminated by
the kidneys, lungs, skin, and liver.

From the histological standpoint the' blood may be regarded
as a tissue. It contains a number of formed elements, represented
by the corpuscles, and an intercellular substance, the plasma,
which is essentially a product elaborated and secreted by all the
cells which take part in haeniatopoiesis and haematolysis. The
blood is distinguished from the other tissues by the fact that it
is fluid and that it circulates, and is therefore capable of exerting
its action on all the fixed tissues, bringing them into relation
and binding them together. It thus functions as the centre of
the vegetative system, and is the agent of metabolism, i.e. of the
material exchanges of the whole body.

III. To compress within a few lines the historical development
of our physiological knowledge of the blood would be a work of
difficulty. In this field there is no one great discovery to be
recorded, only the gradual acquisition of separate facts due to
the labours of a vast number of observers. We shall confine
ourselves to enumerating a few of the principal dates and names
as landmarks.

The Italian Malpighi (1661) was the first who saw the red
corpuscles, while the Dutch Leeuwenhoek (1673) first described
them accurately. In England Hewson (1770) also observed the
leucocytes, found that many salts delayed or inhibited coagulation,.

94 PHYSIOLOGY CHAP.

and foresaw many of the theories that are now generally accepted.
A few years later (1794) J. Hunter published an extensive work
on the blood, which contained not a few new observations and
ingenious experiments. Just as the history of the physics and
morphology of the blood begins only in the seventeenth century
with the discovery of the microscope, so the history of its
chemistry only assumes notable proportions at the commencement
of the nineteenth century, after Priestley (1775) and Lavoisier
(1784) had laid the h'rst methodical principles of modern
chemistry. As the precursors of our present science of haema-
tology, we may name Berzelius (1808), Prevost and Dumas (1821),
Chevreul (1824), Nasse (1842), Simon (1842), Mulder (1849),
Lehmann (1850) and many others.

IV. If we consider the most striking characters of the blood,
it is found to be a red fluid (arterial blood, scarlet ; venous blood,
dichroic, i.e. dark red in reflected, greenish in refracted, light),
somewhat viscous, opaque even in thin layers, faintly salt and
sweetish in taste, with a characteristic odour. It is a little
heavier than water : the specific gravity of a man's blood varies
between 1-057 and 1'066, that of a woman from 1-053 to 1-061.
The reaction of the blood circulating in the vessels is alkaline in
the normal state ; extracted from the vessels, it becomes neutral
and then slightly acid. It must, however, be noted that in all blood
reactions, and, generally speaking, in all the fluids of the body, we
have to distinguish between the actual or true reaction and the
potential reaction.

Eecent researches in physical chemistry have brought out the
fundamental fact that the degree of acidity or alkalinity of a
solution is determined by its content of H + ions and OH - ions
respectively. Since the actual reaction of a liquid is that which
represents its content of free H + or OH - ions, it is necessary
in determining it to make use of means which do not alter the
numbers of these ions. The potential reaction is that which
represents the degree of acidity or alkalinity of a liquid when
the electrolytes which it contains are all fully dissociated into
their ions.

The determination of these two kinds of reaction leads in the
case of the blood to very different results. While according to
the potential reaction the alkalinity of the blood corresponds
to a soda solution of 0'2 - 0'4 per cent, according to the actual

1-3

or true reaction it would be that of IQQQOOOO-^ °^ s°da, which is
practically neutral (Farkas).

The Pycnometric Method is certainly the most exact for determining the
specific gravity of blood in animals, and also in man when there is a sufficient
quantity of blood to work with. A glass pycnometer is used, which carries a
thermometer in its stopper so that the temperature at which the experiment

IV

THE BLOOD: FORMED CONSTITUENTS

95

Fu;. 24.— Pycnometer for de-
termining the specific
gravity of blood.

is carried on can be recorded (Fig. 24). After carefully cleaning and drying
the pycnometer, it is weighed, first empty, then when filled with distilled
water. It is then washed out with alcohol and ether, dried again, and
weighed once more when filled with the blood to be examined. The weighing
must be accurate to iV mgrm. The weight of distilled water at 15° C. being
equal to 1, it is easy to calculate that of blood at the
same temperature. The areometric, method, also used
in physiology, is more rapid, but is less exact than
the pycnometric, because it determines the specific
gravity of the plasma rather than that of the blood
in toto. When only small quantities of blood are
available, as in clinical researches, the capillary
pycnometer of Schmalz is employed, which consists
of a capillary tube some 12 cm. long by 1^ mm. wide,
in which distilled water and 1 tlood are aspirated and
weighed in succession. The weighing and calculat-
ing are carried out as in the first case.

Besides these direct methods of ascertaining
specific gravity for small quantities of blood, there
are other indirect ways which are all based on the
principle of obtaining from a more dense and a less
dense substance a mixture of the same density as the
drop of blood to be examined. This is ascertained
when, on introducing the drop of blood into the
mixture with a pipette, the drop neither sinks nor
rises to the surface. The density of the mixture is
then determined with the areometer, and will be that
of the blood. The various indirect methods differ among themselves according
to the quality of the substances used for the mixture. Fano employs a
solution of gum, Roy a solution of glycerin. It should be noted that these
indirect methods rather determine the specific gravity of the corpuscles than
that of the blood in toto.

When care is taken to employ liquids in which the components of blood
are the least soluble (for example chloroform and benzol, Hammerschlag's
method), these methods can be used with approximate accuracy, and they
may also be employed for the separate determination of the specific gravity
of serum (1028) and of the red corpuscles (1088).

The following methods are used in determining the chemical reaction of
the blood :—

1. Kuhne's Method — The drops of blood to be examined are placed in a
small dialyser, made of moist parchment, shaped by pressure over a hemi-
spherical mould. The drops of blood are introduced into the resulting hollow,
and the whole placed in a watch-glass containing distilled water, to dialyse.
After a certain time the reaction of this water is tested with litmus-paper.

2. Liebreich's Method. — A drop of the blood to be examined is put on a
slab of chalk or plaster, previously saturated with a neutral litmus solution.
After a given time the slab is washed with a vigorous spray of distilled water,
and the spot where the blood-drop lay is found to be more or less blue in
correspondence with its alkalinity.

3. Zuntz' Method. — Glazed strips of neutral litmus-paper are used, which
are saturated with a solution of sodium chloride or sodium sulphate. After
bringing these into contact with the blood to be examined, they are washed
rapidly with a fine spray of distilled water.

The Titration Methods, which consist in determining the quantity of an
acid or alkaline solution of a given strength to be added to the liquid under
examination, in order to modify the colour of an indicator, merely give the
potential, and not the actual, reaction of the fluid. Apart from errors due to
the nature of the indicator, it must be remembered that not only the quantity

96 PHYSIOLOGY CHAP.

of free H -f and OH - ions remaining in the fluid, but, further, the quantity
of H + and OH — set free in consequence of the modifications of chemical
equilibrium between non -dissociated and associated molecules, are determined.
The titration methods most commonly employed to estimate the alkalinity
of the blood are as follows : —

1. Zuntz neutralised the alkalinity of the blood by a titrated solution of,
phosphoric acid, 1 c.c. of which corresponds to OO05 grin, of sodium carbonate.
Litmus-paper is used as the indicator. Lassar, on the other hand, employs a
decinormal solution of tartaric acid (7 '5 grins, of acid per litre).

2. Landois adopts the decinormal solution of tartaric acid, and a perfectly
neutral, saturated solution of sodium sulphate. As indicator he uses the
finest litmus-paper. With these two solutions ten mixtures are made in the
following proportions :—

I. 10 parts -1Q tartaric acid to 100 parts saturated sol. NaS04.

II. 20 „ „ 90 „ „

X. 100 „ „ 10 „ „

The first mixture is then aspirated to a distance of 8 nun. along a
graduated pipette made of a glass tube 1 mm. in diameter, and the blood to a
distance of 16 mm., i.e. 8 mm. of each fluid. This mixture is emptied into
a watch-glass and the reaction tested. Each successive mixture is employed
in the same way until the alkaline solution becomes acid. The degree of
alkalinity corresponding to the several mixtures is as follows : —

I. = 0-036 per cent NaOH. VI. = 0-216 per cent NaOH.

II. -0-072 „ „ VII. -0-252

III. =0-108 „ „ VIII. = 0-288

IV. =0-144 „ „ IX. =0-324
V.= 0-180 „ „ X. = 0-360

Jaksch has modified Landois' method in practice as follows. He too

employs a solution of ^ tartaric acid and a concentrated solution of sodium

sulphate. He dilutes the first solution 10 and 100 times, making solutions of

-- and - — tartaric acid respectively. These solutions are mixed with the

solution of sodium sulphate in eighteen mixtures, which contain : —

I. 0-9 c.c. 10Q acid with O'l c.c. of NaS04.

II. 0-8 „ 0-2

IX. 0-1 ,, „ 0-9

X. 0-90.0.^ „ 0-1
XL 0-8 „ „ 0-2

O'l c.c. of blood is dropped into each watch-glass, stirred up, and the reaction
tested with litmus-paper. The solutions correspond to the following degree
of alkalinity of the blood :—

I. 0-360 NaOH in 100 grms. of blood.

II. 0-320

III. 0-250

IX. 0-040

X. 0-036

XVIII. 0-004

The actual reaction of the blood is measured by the Electrometric Method
(concentration cell). Particulars will be found in any modern text-book of
physics.

iv THE BLOOD : FOKMED CONSTITUENTS 97

The blood has the highly important property of coagulating
spontaneously. In a few moments (3-12 minutes for human
blood) after it has been taken from the blood-vessels it is trans-
formed into a gelatinous mass, which assumes the shape of the
vessel that receives it. It is the formation of this clot which
checks the continuation of haemorrhage in small injured vessels
which would otherwise lead to the death of the animal. Clotting-
depends on the formation and separation of a protein from the
plasma, i.e. fibrin (which, as we shall see, does not pre-exist as such)
in the form of a fibrillar reticulum of such excessive fineness, that
it encloses in its meshes not merely the whole of the corpuscles,
but also the entire liquid portion of the blood. This fact appears
the more marvellous when we consider that the amount of fibrin
formed during coagulation never exceeds 1 per cent of the mass
of blood, but is more often represented by a fraction, O4 per cent,
of this, and may even fall to the minimum of O'l per cent. The
separation of the fibrin from the mass of blood can be effected by
prolonged washing of the clot (Malpighi, 1666), or by whipping
the freshly-extracted blood (liuysch, 1707). In this last case the
fibrin clings to the rod used for whipping as a fibrous, elastic,
whitish mass ; and blood thus defibrinated is incapable of clotting.

From the clot containing the whole mass of blood a yellowish
fluid gradually separates out in consequence of the physical
retraction of the fibrous reticulum, the so-called serum, which
represents that part of the plasma that remains liquid after
coagulation. When all or nearly all this serum has separated out
from the clot, the latter is seen to be considerably diminished in
volume, though it still keeps the form of the vevssel. The clot
thus reduced by the separation of the plasma is sometimes termed
the crassamentum.

In blood which has been rendered incoagulable by defibrina-
tion, the red corpuscles, being heavier than the serum, tend to fall
to the bottom of the vessel, so that an almost transparent upper
layer is formed by degrees, consisting principally of serum, with
an opaque lower layer formed almost exclusively of the mass of
corpuscles. The separation of the serum from the corpuscles is
effected with maximal speed and perfection by the Centrifuge,
which can be performed with the elegant little model represented
in Fig. 25.

If coagulation is delayed in blood newly drawn from the
veins (as is often observed in human blood during inflammatory
diseases, and normally in horses' blood) there is again a partial
separation of the plasma from the red corpuscles, and the clot
subsequently formed presents a greyish superficial layer of greater
or less density, known as the buffy coat, or crusta phlogistica, which
consists of coagulated plasma mixed with leucocytes, without any
red corpuscles.

VOL. I H

98

PHYSIOLOGY

CHAP.

V. The estimation of the total quantity of the blood, or its
relations with the weight of the animal, presents great practical
difficulties. The older anatomists held very exaggerated views
on the quantity of blood in man, estimating it erroneously by the
amount of injection mass that can be forced into the blood-vessels
of a dead body. Far too low values, on the other hand, were
obtained at a later period by the method of completely bleeding
the animal (Herbst, 1822), since this does not sufficiently take
into account the quantity of blood left in the vessels, which may
vary considerably in different cases.

FIG. 25.— Hedin's small centrifuge. By means of three cogged wheels enclosed within 1, 2, 3, each
turn of the handle is multiplied 100 times from the axis A, the apex of which carries a cross-
piece, with the test-tube holders pp, which are kept horizontal during the rotation.

A better method is that carried out by Lehmann and Ed.
Weber on two criminals (1853). They weighed the individuals
before and after decapitation, and from the difference in weight
estimated the mass of blood lost by bleeding. They took a sample
of this blood. They then injected water through the arteries of
the trunk and head, until it flowed almost colourless from the
veins, and lastly determined the weight of the solids contained
in the blood and in the washings. From these determinations
they calculated the quantity of blood left in the body after
decapitation.

It is obvious that this method must give too high a result.
The introduction of water into the vessels must extract not only

iv THE BLOOD: FOKMEI) CONSTITUENTS 99

the fixed constituents of the blood remaining in the system, but
also such as have penetrated by the lymphatic system and by
diffusion from the tissues, during and soon after the bleeding.
In one of the criminals, who weighed 60,540 grins., the mass of
the blood weighed 7520 grins., i.e. one-eighth of the body-weight.
More exact results were obtained with the chromometric
method, which is based on the colouring properties of the blood
pigment (haemoglobin). It was first employed by Welcker (1854)
and was perfected later by Gscheidlen (1873). A little normal
blood is first drawn from the animal and weighed ; the whole of
the blood that can be extracted by bleeding is then collected ;
that left behind is subsequently washed out of the system by
irrigating with a stream of isotonic (0*60-0 '55 per cent) salt
solution ; then, after removing the contents of the gastro-iutestinal
canal, gall bladder and urinary bladder, the viscera are minced up
and soaked for several hours in the saline fluid used for washing ;
lastly, the washings are mixed with the mass of blood obtained
by bleeding. The blood-content is calculated from the coloured
liquid obtained, after determining the quantity of saline that
must be added to the weighed specimen of blood in order to obtain
the same degree of colour. To make the experiment more exact
it is advisable to saturate the haemoglobin with carbon monoxide,
in order to secure the same degree of colour in both mixtures.

The calculation for determining the quantity of blood contained in the
body is very simple : — If a is the quantity of blood extracted in the first
bleeding, x the quantity of blood left in the body, b the quantity of physio-
logical saline employed to wash out the vascular system and organs of the
animal, c the quantity of physiological saline necessary, to make the colour
of the blood a equal to that of the blood x, plus the fluid b (a quantity which
is known to us, and which we may, to simplify matters, denote as d) ;.
it is easy to calculate the quantity of blood x according to the following
equation : —

a 4- c : a : : d : x

and therefore x-=a — ••

a + c

Having thus determined the value x, we can at once arrive at the total
volume of the blood by adding the first portion a extracted in the pre-
liminary bleeding to x : if we then multiply the volume of blood by its
specific weight, we obtain the absolute weight of blood, the relation of which
to the total body-weight of the animal has finally to be calculated.

Welcker came to the conclusion that the mass of the blood
varies in dogs from 7 to 9 per cent of the body-weight, in rabbits
from 5 to 9 per cent. Bischoff (1855), who applied these methods
to the bodies of two criminals, obtained results which approxi-
mated closely to those obtained by Welcker for dogs (7*1 to 7'7 per
cent). Assuming that in man the blood averages ^ of the body-
weight, there would be 5 kilograms of blood in an individual of 65
kilograms body- weight.

VOL. I H a

100 PHYSIOLOGY CHAP.

It goes without saying that the quantity of blood must vary
with the constitution, sex, age, state of nutrition, and with many
other functional or purely individual factors. Clearly, lymphatic
individuals and those whose fatty tissues (which are poorest in
blood) are strongly developed, must have a considerably lessf
quantity of blood than other individuals in whom muscular
tissues which are richly irrigated with blood predominate. The
former may be relatively termed anaemic, the latter plethoric.

VI. The morphological study of the blood is founded on micro-
scopical observations, which show the presence of three distinct
elements — lied Corpuscles (Erythrocytes or Haemacytes), White
Corpuscles (Leucocytes), and Platelets (Hayeni's Haematoblasts).

The Erythrocytes are in the form of biconcave discs, non-
nucleated and round in all mammals (save the camel and the llama,

FIG. 26.— Form and relative size of erythrocytes of different animals, viewed from the 'surface.
1. Erythrocyte of musk-deer ; 2, goal; 3, marmot; 4, llama; •'>. man; <], pigeon; 7, tench;
8, lizard ; 9, frog ; 10, proteus.

in which they are elliptical) ; nucleated and elliptical in birds,
reptiles, amphibia and fishes (Fig. 26). The red corpuscles of
man have a diameter of 7-8 ^ and a depth of 1'7 /x ; in other
mammalian animals they are even smaller; in birds and the
lower vertebrates they are much bigger (21 /x in frog, 29 /x in
Triton, 58 /x in Proteus). Viewed from above, and isolated, they
are greenish-yellow in colour ; seen from the side as a rouleau of
discs, they are red (Fig. 27) ; to them the blood owes its char-
acteristic colour, and they render it opaque. They are soft,
almost gelatinous in consistency — hence they easily change their
shape ; but they are perfectly elastic, and recover their original
form directly the contracting force ceases to act on them.

Pted corpuscles may be divided, according to their affinity for
staining, into orthochrornatic and polychromatic (Ehrlich). The
orthochromatic are the most numerous, and stain with aurantia
and eosin. The polychromatic, which are much less frequent,
take up fuchsin when they are stained with tri-acid ; with eosin-
methylene-blue they stain violet, etc. Red corpuscles are classified

iv THE BLOOD: FOKMED CONSTITUENTS 101

according to their form and size (distinctions which concern the
pathologist) into normal erythrocytes, micro- and macrocytes,
and poikilocytes (pear-shaped, rod -shaped, etc.). Again there
are red corpuscles which exhibit granules of different si/es and
shapes in their protoplasm, and which will stain with all the
basic dyes (basophile granulation). On changing the stains, the
figures produced assume quite different forms ; this shows that
the figures that we see do not correspond exactly with the pre-
existing arrangement of the chromatic substance, but depend on
the different physico-chemical actions exercised by each individual
colouring substance (Cesaris Demel). The significance of these
granules is uncertain ; by some they are considered to be the
remains of nuclei, according to others they are protoplasmic
formations.

FIG. 27.— Red blood-corpuscles of man. (Magnification, 650 diameters.) Some are seen flat, others
in profile, the majority are disposed in rouleaux.

Although Schultze has described active movements of the
protoplasm in the nucleated erythrocytes of the chick, it is very
doubtful whether the red corpuscles of mammalia are capable of
expanding and contracting in the medium in which they normally
live. When, however, they are taken out of the vessels, and cooled
or warmed, or excited by induction shocks ; when the degree of
concentration of the plasma in which they float is altered by the
addition of water or of saline solutions ; when they are brought in
contact with extraneous chemicals, — they readily change their shape,
assuming a mulberry-like or even prickly (crenate) appearance,
and extending or retracting different segments of their protoplasm,
as if undergoing amoeboid movements. The former changes are
the effect of altered osmotic conditions, the latter are probably
to be regarded as active movements (Figs. 28 and 29).

The capacity of erythrocytes for active movements in certain
special abnormal conditions is confirmed by the observations of
A. Cavazzani. He noticed that when blood was collected in an
isotonic or hypotonic solution of sodium chloride, to which potassium

102 PHYSIOLOGY

CHAP.

ferrocyanide or a highly dilute solution of potassium sulpho-
cyanide had been added in the proportion of about 1 per 1000,
and then examined under the microscope at a temperature of
35-37° C., the erythrocytes of man and other mammalia (not
of birds and batracians) put out delicate prolongations like cilia,
the rapid vibratory movements of which enable the corpuscles
to oscillate, rotate, or move forward. These cilia-like pseudopodia

* # • O

FIG. 28. — Successive effects upon erythrocytes of discharge from a Leyden jar. (Rollett.) a,
normal erythrocyte ; b, rosette form ; c, mulberry form ; <1, prickly form ; e, rounded and
swollen erythrocyte ; /, ghost.

rise from the smooth surface of the erythrocytes, and vary in
length and number. Their movements of expansion and retraction
are slow and limited. If a drop of solution of cocaine hydrochloride
is added to the preparation, the erythrocytes resume their former
shape in a few moments. If washed free of the cocaine, and
treated afresh with the ferrocyanide, they may resume their
ciliated aspect.

Since, according to the researches of Albertoni, cocaine paralyses
protoplasm, it follows that the changes of form exhibited by the

erythrocytes under the influence of potas-

a 5 c ^ sium ferrocyanide must be considered as

fl Q ft @ \^) active movements of the protoplasm. Ery-

throcytes have a fairly tenacious vitality.

When taken out of the blood - vessels and
a C^ reinjected, they survive after as much as
^^ 4-5 days, but only provided they are kept

FIG. 29.— a, Successive effects upon • • Tf ViPq4-p^ fn KO0 p flipv rlio an/1

erythrocytes of water (Schafer) ; * lce- teateu tO OZ 1^., Uiey QIC ana

b, action of a solution of salt ; break up when reintroduced into the

c, action of tan me acid. . -.*

circulation. If transfused into animals ol

a different kind they do not survive, but degenerate and disin-
tegrate more or less rapidly, owing to the heterogeneous plasma
with which they are brought in contact.

The direct enumeration of the corpuscles contained in a given
quantity of blood (1 c.mm.) was correctly performed for the first
time by Vierordt and Welcker (1854), the results they obtained
having been confirmed by more recent observers. The method
and apparatus have been perfected, and are now practical and
easily applicable for clinical purposes. We must here confine
ourselves to naming those of Malassez, Hay em, and Thoma-Zeiss.

Haemacytometer of Thoma-Zeiss. In order to count blood -corpuscles with
the Thoma-Zeiss apparatus, the point of the capillary glass pipette (Fig. 30,
I) is dipped into the drop of blood to be examined, which is obtained by

IV

THE BLOOD: FOKMED CONSTITUENTS

103

pricking the finger with a needle. A column of blood is aspirated by means
of the rubber tube to division 0'5 or 1 of the pipette, and after 'quickly
drying the lower end, the bulb of the pipette is filled up to the figure 101
(which expresses its capacity in c.mm.) with 3 per cent salt solution, or with
Pacini's fluid as modified by Hayem and Gram (corrosive sublimate 0'5 grin.,
sodium sulphate 5 grms., sodium chloride 2 grms., distilled water
200 grms.). It is then sufficient to shake the pipette for a few
moments in order that the glass ball (a), which is loose inside
the bulb, may mix the blood with the salt solution, and make
the fluid homogeneous. As the division 0'5 corresponds exactly
to -y^ of the total capacity of the bulb, and the figure 1
exactly to T^y, we know that the mixture obtained is in the
ratio of 1 : 200 or 1 : 100.

The counting is done upon a carrier (II) of thick glass
with a groove (6), the bottom of which is divided by lines cut
with a diamond into 400 minute squares (as is shown in III).
Into this groove, the capacity of which is O'l c.mni., a drop of
the blood solution contained in the bulb of the pipette is intro-
duced, care being taken to drive out the liquid contained in the
capillary portion, which has not been mixed with the blood.
When the drop is placed in the groove, a cover glass (a) is
quickly applied, and after letting the preparation rest for a few
minutes upon a perfectly horizontal surface, in order that the
red corpuscles may be spread evenly upon the floor of the groove,
the counting is undertaken under a magnification of 200

II

0 «

ni

FIG. 30. — Thoina-Zeiss Haemacytometer. I, Graduated pipette (Potain's mixer) ; II, cell for
counting corpuscles, side view ; III, squared divisions of bottom of haemacytometer.

diameters. The number of the corpuscles counted is divided by the number
of squares examined, which should never be less than 200 ; thus obtaining
the average of the red corpuscles contained in each square, which represents
pAnr c.mm. Hence, if we wish to know the number of corpuscles in c.mm.
it is only necessary to multiply the number found first by 4000, and then
by 100 or 200, according as the blood has been diluted iOO or 200 times.
To take a practical example : — If 1225 corpuscles are counted in 250 squares,
VOL. I H 1)

104 PHYSIOLOGY CHAP.

and the blood has been diluted 200 times, 1 c.mm. of blood will contain

1 99 r,

£ x 4000 x 200 = 3,920,000 red corpuscles.
250

The white blood-corpuscles can be counted at the same time ; but if a
separate enumeration is desired for the sake of accuracy, the blood must be''
agitated with a 0*3 per cent solution of acetic acid, in which the red corpuscles
will dissolve while the white remain intact.

Hedin's Haematocrit is an apparatus for determining the total volume of
red corpuscles in 100 parts of blood. It consists of a small centrifuge (Fig. 25,
p. 98) and of two graduated tubes (a, «', Fig. 31). The determination is
carried out as follows : — A small quantity of Miiller's fluid (sodium sulphate 1
grm., bichromate of potash 2 grins., distilled water 100 grins.) is taken up with
a pipette, and dropped into a small porcelain dish. The finger is then pricked
with a lancet so as to obtain a large drop of blood. With the same pipette a
quantity of blood equal to the quantity of M tiller's fluid is taken up, and
emptied into the same dish. The two fluids are then thoroughly mixed with
a glass rod, with the double object of retarding the coagulation of the blood
(the mixture will not clot under half an hour) and of fixing the red corpuscles
in their natural size. The graduated tube is then filled with the mixture
thus obtained, by taking up the fluid from the dish directly into the tube,

Fin. 31.— Hedin's Haematocrit— substitute for test-tube holder of Fig. ~2'>, p. us. a, a', Graduated
tubes, kept in the hollows prepared for them by the presence of two elastic springs; 6, ?/,
small metal rods that compress the spirals in loosening or tightening the tubes.

which has previously been fitted with a rubber tube furnished with a mouth-
piece. The tubes have a calibre of 1 sq. mm., and are. divided into 50 parts.
The filled tubes are then fixed to a horixontal holder (shown in Fig. 30), which
replaces the test-tube holders, pp, of the centrifuge (Fig. 25), care being taken
not to lose any of the fluid. They are now centrifuged for five to seven
minutes with a velocity of 80 turns per minute of the handle of the apparatus,
which corresponds to 8000 revolutions of the tubes, until the red corpuscles
separate out into a compact and well-marked column, the volume of which
will not shrink further. Since the tubes have very thick walls, and the
graduation is cut on the surface, errors may occur in the reading which are
due to the different positions of the reading eye. The inventor of the
apparatus has calculated this error as equal to 0'2 degree of the scale, and
to avoid it suggests that the reading be carried out by looking along a glass
plate held at right angles to the tube. From the volume found, the volume
of corpuscles in 100 parts of blood can be determined by multiplying the
volume of the column of blood-corpuscles by 4. As two determinations of
the volume of the erythrocytes are made at the same time, these form a
reciprocal control

Since the total volume of the mass of corpuscles is proportional to the
relative number of the erythrocytes, this method can be substituted for that
of Thoma-Zeiss, which takes much longer to carry out.

Many series of determinations on the relative mass of corpuscles
have been worked out, on man as well as animals, in order to

iv THE BLOOD : FOKMED CONSTITUENTS 105

ascertain the variations due to age, sex, constitution, functional
state of the body, various morbid conditions of the blood, and so
on. As an average it may be taken that 1 c.mrn. contains 5,000,000
red corpuscles in a man, 4,500,000 in a woman ; that they are
more abundant in venous than in arterial blood ; less abundant
in adolescents than in adults, more numerous in new-born infants
than in the mother ; that all the influences that induce a marked
loss of water in the body increase their number, while a high
intake of water diminishes them ; that they multiply with every
improvement in the external and internal conditions of life, while
poor food and a vast number of morbid conditions tend to reduce
them.

It is remarkable that the lowering of atmospheric pressure
on high mountains produces a considerable increase in the number
of erythrocytes (Viault). The same effect has been observed in
mice on rubbing their skin with croton oil, and on prolonged
exposure to strong electric light (Kronecker). It should also be
noted that not merely scanty nutrition, but even an absolute fast
of thirty days, produces no marked variation in the number of
the erythrocytes (Luciani). Obviously the relative quantity of
corpuscles, which depends upon the degree of concentration and
amount of water contained in the blood, can rarely yield a safe
conclusion as to the absolute quantity to be found in the total
mass of blood.

The volume and surface of the erythrocytes have been
approximately determined, by using models of enormous magnifica-
tion ; 5,000,000 corpuscles are found to have a volume of about
\ c.mm. and a surface of 610 sq. mm.

The specific gravity of erythrocytes is, as already stated,
greater than that of plasma and serum (rOSS-TlOS). The weight of
the corpuscles contained in 100 grins, of defibrinated blood is not
far short of that of the serum, averaging a weight of 48 grms. in
man and 35 grins, in woman. Given a man of 78 kilograms,
whose blood amounts to •£% of his body-weight, the total weight
of the erythrocytes would be about 2 kgrm., with a total surface
of some 3840 sq. metres.

VII. The pigment which colours the erythrocytes is a
compound of highly complex chemical structure, known as
Haemoglobin. Under physiological conditions it is entirely absent
from the plasma, and exclusively saturates the colourless spongy
mass of the corpuscle, termed by Eollet the stroma. This fact
suggests that it may be in chemical combination with one of the
constituents of the stroma, perhaps with the lecithin (Hoppe-
Seyler). But the most certain and. -most important property of
the pigment, and that on which the capital function of the
erythrocytes depends, is its affinity for oxygen, with which it
combines as soon as the partial pressure of the gas reaches a

106 PHYSIOLOGY CHAP.

certain value, forming oxy haemoglobin, which with a fall of the
partial pressure is again reduced to haemoglobin. It prevails in
the form of oxyhaemoglobin in arterial, as haemoglobin and
oxy haemoglobin in venous, exclusively as haemoglobin in asphyxia 1 '"
blood.

There are many physical and chemical means by which the
pigment is easily separated from the stroma of the corpuscles and
dissolved in the plasma. Among the physical methods are
warming of the blood to 50-60° C., repeated freezing and thawing,
the discharges of a Leyden jar, induced or galvanic currents;
among the chemical methods, simple dilution with water, addition
of ether, chloroform, dilute alcohol, acid or alkaline solutions, bile,
heterogeneous serum, etc. By using sodium chloride solutions of
various concentrations, different degrees of diffusibility of pigment
can be detected in different corpuscles and different individuals.

According to Winter's researches (1896), the isotonic solution,
i.e. that which has the same degree of molecular concentration as
the corpuscles (and therefore produces no disturbance of osmotic
relations and no diffusion of haemoglobin in the plasma); is repre-
sented by a solution of about 0'91 per cent NaCl in distilled
water.

In proportion as the pigment separates out from the stroma,
the corpuscles grow pale, and finally change into roundish,
colourless, almost transparent bodies which have been termed
ghosts (JBlutschatten), because they are almost invisible. They
stain brown with iodine and can thus be detected.

In order to study the chemical composition of the stroma of
the erythrocytes a large mass of blood corpuscles must be collected,
separated from the plasma, washed with dilute solution of sodium
chloride, and completely freed from haemogloblin by the addition
of 5-6 volumes of distilled water. By this treatment all is
removed save the stroma, which forms a gelatinous mass and can
be separated by filtration from the watery solution.

The small amount of matter remaining on the filter dissolves
in dilute salt solution, and gives all the reactions of globulin.
But the stromata separated from the erythrocytes of birds contain,
in addition to globulin, a considerable quantity of nuclein, derived
from the nuclei of these corpuscles (Plosz, Hoppe-Seyler). Kossel,
with dilute hydrochloric acid, also extracted a substance belonging
to the albumose group, to which he gave the name of histone.

If further chemical researches prove that the erythrocytes
of mammals contain no nuclein, this would be an additional
proof that they really are non-nucleated, which has been denied
by some observers.

An ethereal extract of a mass of stromata yields the other
organic components of protoplasm, lecithin and cholesterin.

The inorganic substances of the stroma consist of potassium

IV

THE BLOOD : FOKMED CONSTITUENTS

107

phosphate and potassium chloride ; in man, and a few other
animals only, there is also a small amount of sodium chloride.

The water content of the erythrocytes is very low as compared
with other organs. In man it reaches only 5 7 '7 per cent, while
in the muscles and glands it amounts to 75 per cent (Hoppe-
Seyler).

The dry substance of the erythrocytes consists principally of
haemoglobin (87-95 per cent), so that the stroma is a very small
amount (13*5 per cent). For the total quantity of the blood,
about 13*8 per cent haemoglobin lias been calculated for man, and
about 12'6 per cent for woman.

Hoppe - Seyler was the first to investigate the chemical
properties of haemoglobin (1860-71 ) and to recognise that although
it is a colloid body, it is
capable of crystallising in
different forms in different
animals, all, however, belong-
ing to the rhombic system
(with the exception of
squirrel's blood, which crys-
tallises in hexagonal plates ;
Fig. 32). To obtain crystals
of pure haemoglobin, they
must first be dissolved in the
blood by freezing and gradual
melting ; the blood in a layer
2 mm. deep is then allowed
to evaporate slowly in a flat,
wide-bottomed capsule.

The different forms of
oxyhaemoglobin crystals, the
different quantities of water of crystallisation which they contain,
their different solubilities and different resistance to decomposing
agents, in short the varying results of elementary analysis, all point
to the conclusion that oxyhaemoglobin is not identical in different
animals. It is a highly complex, iron-containing protein, the
formula of which was determined by Hiit'ner from analysis of
the haemoglobin of dogs' blood. Each molecule of haemoglobin
combines with a molecule of oxygen to form oxyhaemoglobin.

Haemoglobin has a greater affinity for carbonic oxide than for
oxygen, and forms with it carboxy haemoglobin, which, unlike
oxyhaemoglobin, doas not reduce with deoxidising agents. While
carbonic oxide turns out oxygen, the latter has difficulty in
driving carbonic oxide out of its combination with haemoglobin.
To this fact is due (in part, if not wholly) the toxic action of
carbon monoxide.

With a series of oxidising agents, particularly with nitrites,

52. — Haemoglobin crystals. (Funke.) «, From
man ; b, guinea-pig ; c, squirrel.

108

PHYSIOLOGY

CHAP.

FIG. 33. — Haeiuiu crystals. (Preyer.)

permanganate of potash, potassium ferricyanide, active oxygen,
hydrogen peroxide, etc., haemoglobin is converted into methaemo-
globin, which is an isomer of oxy haemoglobin, but in which the
oxygen is more closely combined, so that it cannot be driven out
by the unaided vacuum. Methaemoglobin can also be formed jn

circulating blood by the excessive
use of chlorate of potash and
other substances used in medicine
in recent years as antipyretics.

Haemoglobin undergoes spon-
taneous decomposition slowly
under the influence of air and
water, rapidly as the effect of
acids or alkalies, or of heating.
Another iron -containing pigment
is thus formed, haemochromogen,
which oxidises readily in the
presence of oxygen and is con-
verted into haematin, which gives
a brownish colour to the solution.
Along with haernochrornogen and
haematin, the decomposition of haemoglobin gives rise to con-
siderable quantities of acid or alkali albumin, according as acids
or alkalies are used to break up the blood pigment. From these
facts Hoppe-Seyler regards haemoglobin as a protein, which con-
sists of an albumin, associated
with an iron-containing pigment,
haemochromogen. One hundred
parts of haemoglobin contain
ninety-six parts albumin and four
parts pigment. Haemin must
be noted among the decomposi-
tion products of blood pigment on
account of its great practical im-
portance ; it crystallises in the
form of small rhombic plates or
rods, of a shining brown colour
(Pig. 33). Haemin crystals are
of great importance in forensic

medicine, in the detection Of FK, 34.-Haematoidin crystals. (V. Frey.)

blood-stains. A trace of dried

blood suffices to obtain them. A grain of sodium chloride is-
added, dissolved in a few drops of glacial acetic acid, and cautiously
heated over a spirit lamp until gas bubbles are formed.

Haemin is haematin hydrochloride, and to obtain pure haematin
it is necessary to start from this combination. It is a sulphur-free
compound, but is richer in iron than haemoglobin. When treated

iv THE BLOOD: FOKMED CONSTITUENTS 109

with sulphuric acid, the haematin loses its iron and takes up water,
turning into haematoporphyrin, an iron -free pigment somewhat
resembling haemoglobin in colour.

Another iron - free derivative of haemoglobin, which forms
spontaneously in a crystalline form in the corpora lutea and in
old haeinorrhagic foci, is haematoidin (Virchow), now regarded by
chemists as identical with bilirubin, one of the principal bile-
pigments (Fig. 34).

,It seems clear that all the colouring matters of bile and urine
are derived from successive transformations of blood pigment; but
with the exception of bilirubin, which forms spontaneously, only
one of the urinary pigments, urolilin, has at present been produced
artificially from haemoglobin or haematin.

Many of the pigment substances above recorded, haemoglobin,
oxyhaemoglobin, carboxyhaemoglobin, methaemoglobin, haeniochro-
mogen, haematin, haematoporphyrin, urobilin, possess the important
property, when examined in layers of known thickness and con-
centration, of absorbing well-determined and distinct zones of the
spectrum in aqueous solutions, acid or alkaline, as shown in Fig. 35.
It is important to note that while haemoglobin shows a single
absorption band between the Fraunhofer D- and E - lines,
oxyhaemoglobin and carboxyhaemoglobin show two bands that
almost coincide in the two cases, lying practically within the
same region of the spectrum. Apart from the different tint
exhibited by oxy- and carboxyhaemoglobin, the former being the
pinker, they can, however, readily be distinguished by adding a
reducing substance, e.g. carbon disulphide, to the two solutions,
when the spectrum of oxyhaemoglobin is speedily transformed
into that of haemoglobin, while the spectrum of carboxyhaemo-
globin undergoes no modification.

To determine the relative quantity of haemoglobin contained in a given
quantity of blood, several instruments have been adopted. The simplest and
most convenient Haemoglobinometer is Gowers' apparatus, provided with a
standard solution of CO-haemoglobin. The method, as accurately described
by Haldane,1 gives extremely good results.

For more accurate quantitative determination, either of the haemoglobin
or of the pigments derived from it, the Spectro-Photometric Method must
be employed.

This method- is based on the law that the coefficient of extinction of any
coloured solution is (for any given zone of the spectrum) directly proportional
to its concentration, i.e. C : E=C' : E', when C and C' indicate the correspond-
ing coefficient of extinction, By coefficient of extinction of a fluid is meant
the. negative logarithm of that intensity of light which remains after it has
traversed a liquid stratum of the depth of 1 c.c. (Kriiss, Kolorimetrie u.-quantit.
Spectmlanalyse, 1891).

HC V

From the above equation it follows that -—:=—; this ratio, known as

& si,

that of absorption, is a constant for the same colouring substance. Now, if

1 Journ. of Physiol. xxvi. 497.

PHYSIOLOGY
D E b

CHAP.

6

S

9

10

Fia. 35. — Absorption-spectrum of blood-pigment and its derivatives. 1, Oxyhaemoglobin ; 2, haemoglobin ;
3, methaemoglobin and haematin in acid solution ; 4, haematin in alkaline solution ; 5, haeinatoporphyrin
in acid solution; 6, haematoporphyrin in alkaline solution ; 7, haemochromogen in alkaline solution'; 8,
earboxyhaernoglobin and carboxyhaernochromogen ; 9, sulpho-inethaemoglobin ; 10, hydrobilirubin and
urebilin in acid solution.

IV

THE BLOOD: FOKMED CONSTITUENTS

111

the absorption ratio be represented by A, the coefficient of extinction by E,
and the content of colouring matter in 1 c.c. (calculated in grams) by C, it
follows tkat C will be equal to A x E.

The most exact of the various instruments constructed for the determination
of coefficients of extinction is that of Kriiss. This (as shown by Fig. 36)
resembles an ordinary spectroscope and differs from the spectre-photometers
of Vierordt, Hiifner and others, in that the two slits//' (Fig. 38) which give
the two spectra, one above the other, enlarge and contract in both directions
with a single movement of the screws V and V.

To use this apparatus, fill a small pipette of capillary bore with blood to a

FIG. 36. — Spectrp-photometer of Kriiss viewed as a whole. The extreme end of the eye-piece is
.shown in Fig. 37. The extreme end of the objective is shown in detail in Fig. 38. The
lettering corresponds. The absorption-chamber containing the solution of the pigment, to be
examined is shown in Fig. 39. The third branch x, illuminated by a gas flame, projects the
millimetre scale on to the spectrum.

given capacity, say 20 c.mm. This blood must be rapidly expelled into a
small beaker in which a measured quantity of distilled water has first been
placed, so that the blood is diluted in known measure. The degree of
dilution varies with the greater or less colouring power of the blood to be
tested, but as a rule the ratio of 1-200 is preferred. The pipette which held
the blood should be washed out several times with the water used for dilution,
and the liquid must be agitated till it is homogeneous in colour. The
absorption chamber (Fig. 39), which is a crystal cell with parallel faces, is
then filled, and a cube of glass, D, of the exact diameter of 1 cm., introduced,
to which the name of Sclmltz' cube is given. The two absorption spectra
are those of two strata of the same fluid differing by 1 cm. in depth.

The extinction coefficients for human pxyhaemoglobin have been deter-
mined in two different regions of the spectrum, i.e.

D 32 E - D 54 E and D 63 E - D 24 E ;

112

PHYSIOLOGY

CHAP.

ill which Hiifuer has determined the absorption ratios or constants for, viz. :
0,001330 and 0,001000 respectively.

The limits of these spectral positions, which are comprised between the
Fraunhofer D- and E- lines, may be expressed in wave-lengths by means'/

FIG. :57.— W, Micrometer screw, divided into hundredths, each turn of which displaces the index of
the scale S by one division. This serves to regulate and measure the width of the slit /, which
can be carried by a horizontal movement to the centre of the eye-piece. /,-, Micrometer screw
divided into hundredths, eacli turn of which displaces the index of a scale n by one division.
This moves the eye-piece by an angular development to carry it to any given region of the
spectrum.

of the table published by Kriiss (as above cited). In practice they can be
obtained by finding 011 the illuminated scale of the spectrum (Fig. 36, s)
the values corresponding to the two wave-lengths calculated, and limiting

the spectral region which these
comprise; by the horizontal screw
of the telescope (Fig. 37), and that
marked W, which controls the
slit / of the eye-piece. The ab-
sorption chamber A is then placed
on its support between the plane
of the spectrum and the source of
light, taking care that the upper
surface of the cube D corresponds
exactly with the line of division
between the first and second slit,
and that the aperture of these
corresponds to a complete turn of
the screw : a turn divided into
100 parts, as shown on the scale
affixed to the screws v and v' in
Fig. 38.

On then looking through the
F"Y : ~*Z' r' Mi?rom«ter screw di}'id«l I"*? instrument, two positions of the

hundredths, serves to widen or narrow the slit /./, 4. ill i • 'vi i i

by simultaneous displacement of the two plates spectrum Will be Visible, Olie below

that confine it. the other : one is brighter, corre-

sponding to the cube of Schultz,
the other obscured by the absorption due to the solution of oxyhaemoglobin.

The slit corresponding to the brighter part of the spectrum is then
narrowed until it assumes the same tone of light as the other, and the
scale on the screw read to show how many turns were required to produce
uniform obscurity. From this number, which indicates the intensity of the

l.e........a.

...e e...

,

B~ ft (—}
m^ — \^i

X

f-/'

•:'V. . o

I

. „._ v^-ijij r

L

..w._.xJj|.| V^»

-$^-^~

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-"'''' °

_^^_ /*JV- -X^V

V^7 *<^/ ^7

•"9 "0"

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IV

THE BLOOD: FORMED CONSTITUENTS

113

light remaining after tlie luminous rays have traversed the colouring matter
of the blood, the negative logarithm that represents the extinction co-efficient
can be calculated, and this must be multiplied first by the constant of the
spectral tone obtained, and then
by the degree of dilution of the
blood. Thus it is calculated how
many grams of haemoglobin are
contained in 1 c.c. of blood.

Practical Example. — Let the
blood under examination have
been diluted 200 times, and the
first spectral region be that, in
which the constant is 0-001330,
the intensity of the remaining
light will be found to be 0-255 ;
to calculate the amount of oxy-
haemoglobin contained in 1 c.c.
of the blood, multiply 0*001330
by 200, and then by the negative
logarithm of 0'255, i.e. by 0'5935.
In this case the oxyhaemoglobin
of 1 c.c. of blood will be equal to
0-1578 grm.

VIII. The White Blood

Or LeUCOCyteS are FIG. W.—A, Absorption-chamber with parallel faces;
pnrl nnrrmlpf-p r>pll« prm 7)> Schultz* cube, made of glass 1 c.c. in depth, in-

ana Complete CeilS, COU- traduced into the chamber.

sisting of naked granular

protoplasm, with one or more nuclei, which are not easy to dis-

FIG. 40. — Different kinds of human leucocytes examined either in the fresh state, or after fixation
with various reagents, magnification about 1000 diameters (partly from Kanthack and Hardy).
a, a,', b, Fresh leucocytes of three different sizes, in the resting state ; c, the same in amoeboid
state ; d, polynuclear acidophile leucocytes with )arge (d') and line (d") granulation ; e, e', c",
hyaline leucocytes, destitute of grannies ; /, lymphocytes ; g, leucocytes with basophile
granulation.

tinguish in the fresh state, but may become very conspicuous on
adding a drop of acetic acid to the microscopic preparation.
VOL. I I

114 PHYSIOLOGY CHAP.

The varying character of the protoplasm and nucleus make it
possible to distinguish several kinds of leucocytes. From their
size, and probably from their various grades of development^
Schultze recognised three varieties ; the smallest attain at most a
diameter of 5 //, and possess a large nucleus, the medium have an
average of 7 /*, the largest of 9 /x ; the latter are often multinuclear
and of irregular external shape. In the foetus of less than four
months there are still larger ones which may reach 15-19 /* (Fig. 40).

According to a more rational classification proposed by Ehrlich
and Engel, leucocytes are divided into two classes: those with
and those without granules. The leucocytes with granules are
distinguished as mononuclear and polynuclear, and by their
staining affinity, as acidophile, neutrophile, and basophile.

Mononuclear leucocytes with granules are extremely rare, or
entirely absent, in normal circulating blood; according to many
authors they represent the transition forms to polynuclear
correspondents. Polynuclear neutrophile leucocytes constitute
the greater part of the white corpuscles (from -3- to f)«-.they have
a diameter of 9-10 //, exhibit lively amoeboid movements, and
perform the function of phagocytosis. Polynuclear leucocytes
with fine or coarse acidophile granulations are very scarce
(from 2 per cent to 4 per cent). Still rarer in the circulating
blood are those with basophile granulations (0*5 per cent) ; they
are found almost exclusively in the tissues of the haematopoietic
organs.

The non-granular leucocytes are distinguished as lymphocytes,
large lymphocytes, large mononuclear cells and inflammatory
forms. The lymphocytes are the size of normal erythrocytes, with
a reticular nucleus which occupies nearly the whole cell. They
represent about | the total number of white corpuscles; their
number varies not merely in certain physiological conditions, as
for instance in digestion, but also in pathological states.

The large lymphocytes, large mononuclear cells, and in-
flammatory forms have precisely similar characters to the pre-
ceding ; they are differentiated by the volume of their protoplasm.
These cells are comparatively rare in normal blood, and are more
interesting to the pathologist than to the physiologist.

Many clinical, anatomical, and experimental researches have
been directed to the object of establishing the relations existing in
last resort between the lymphocytes and the granular leucocytes
with polymorphous nuclei, as well as the general relations
between the various white morphological elements of the blood.
Here we must only say that while Ehrlich's theory admits a sharp
distinction between the cells derived from the lymphatic system
and those derived from bone-marrow, there is another opposing
theory, according to which the lymphocytes are the young cells
which give rise to all other elements of the blood (Ouskoff).

iv THE BLOOD: FOKMED CONSTITUENTS 115

Notwithstanding these different theories and conflicting argu-
ments, Ehrlich's view is that generally supported.

In the circulating blood the white corpuscles are almost always
round, and since their specific gravity is somewhat lower than
that of the erythrocytes, they leave the more rapid axial current
of the vessels and follow the slower peripheral stream, keeping in
perpetual contact with the internal walls of the vessels and con-
stantly rotating along them (cycloid movement). When observed
in an isolated drop of blood, the object-carrier of the microscope
being warmed to 35-40° C., it is easy to recognise their mobility,,
which exactly resembles that of the Amoeba, so that Lierberktihn
(1854), who was the first to study and describe them exactly,
regarded leucocytes as peculiar parasitic amoebae. It is more
interesting to watch the amoeboid movements of the leucocytes
within the blood -stream. Cohnheim (1869) was the first to
demonstrate the fact that leucocytes, by their amoeboid properties,
are capable of perforating the internal walls of the smallest veins
by a pseudopodium and of passing their whole body, little by little,
through the temporary wound thus formed, as through a mesh,,
emigrating in this way from the blood torrent into the interstices
or plasma canals of the tissues. This emigration may become
tumultuous in tissues that have suffered inflammatory irritation
(natural or experimental). The pathological doctrine of suppura-
tion and formation of abscesses is definitely co-ordinated with
this fact. The more recent researches of Thomas, Eecklinghausen
and others have demonstrated that corpuscular diapedesis must be
regarded not as a passive extravasation, but as an active emigra-
tion due (as was Cohnheim's original idea) to the amoeboid
mobility of the leucocytes.

The discovery of Phagocytosis, founded more particularly on
the elegant researches of Metschnikoff (1892), added new and
interesting arguments for the close approximation between
leucocytes and amoebae. Even when removed from the blood, and
observed with the microscope, leucocytes, like amoebae, are seen to-
be capable of ingesting many foreign bodies, by surrounding them
with protoplasm, whether these are inorganic particles (such as
carmine granules and other colouring matters), fat drops, dead cells
or fragments of cells, or living cells and microbes '(e.g. erythrocytes-
and bacteria) of various pathogenic or non-pathogenic species.

Leucocytes, like amoebae, are capable of digesting dead bodies,,
and of chemically killing and dissolving the living cells and
microbes which they have ingested. The red corpuscles thus-
dissolve slowly in the interior of the phagocytes (large leucocytes),,
leaving a residue of pigment. They exercise a similar dissolving
action upon pus granules (dead or dying leucocytes), on the fibrin
of inflammatory exudates, and on muscle fibres in cases of acute
atrophy of the muscular tissue. Lastly, the phenomenon of the

VOL. I i a

116 PHYSIOLOGY CHAP.

digestion of the microbes englobed by leucocytes (anthrax bacilli,
spirilli of recurrent fever, vibrios of septicaemia, streptococci of
erysipelas) have been directly observed in various phases. These
facts are much in favour of Metchnikoff s view that the protoplasm
of leucocytes contains enzymes which are more active than the
secretions of the digestive glands of higher animals (pepsin and
trypsin), since the latter fail to kill the same microbes.

According to Leber, Massart, Bordet and other observers, the
migratory and phagocytic faculties of the white corpuscles are
phenomena of chemotaxis (i.e. the property of being attracted or
repelled by certain chemical compounds, even at a distance). It
is a fact that leucocytes do not devour all the species of microbes
which they encounter in their wanderings, but are capable (at least
up to a certain point) of selecting the prey on which they feed.
In the body the physiological function of the leucocytes depends
essentially, as we shall see below, upon their phagocytic capacity.

The number of leucocytes varies conspicuously, even under
physiological conditions. This may— partially at leas-t — be ex-
plained by the fact that they are continually (in different degrees,
according to the functional state of the viscera) emigrating from
the lymphatic system, in which they originate, to the vascular
system, and thence again by diapedesis into the lymphatic system.

The method for counting leucocytes is fundamentally the
same as for the enumeration of erythrocytes. In normal blood
their number is much lower than that of the erythrocytes.
According to Grancher, there are in healthy young people of
twenty to thirty, 3000 to 9000 leucocytes in 1 c.mm. at different
hours of the day. The ordinary ratio between these and the
•erythrocytes would be from 1:1200 to 1:1500, but it may increase
to a maximum of 1:900. According to Malassez, on the other
hand, there are 4000-7000 leucocytes per c.mm. in healthy persons ;
and the ratio with the erythrocytes is from 1:1250 to 1:1650.
It must always be remembered that the number of leucocytes
varies according to the vascular region from which the blood is
drawn, and with age, season, state of nutrition, in menstruation,
pregnancy, etc. Disease has the greatest influence on the number
of leucocytes; during suppuration, but especially in certain
morbid states (leucaemia), their numbers may be enormously
increased, and their ratio with the red corpuscles may rise to 1:15
or even higher. On the other hand, it should be noted that the
opposite occurs during the first week of an absolute fast, when
there is marked and progressive diminution of the leucocytes
(Luciani).

It has not hitherto been found possible to examine the
chemical composition of the leucocytes of the blood, owing to the
difficulty of separating them from the plasma without admixture
of other elements. The first observations on this subject were

iv THE BLOOD: FOEMED CONSTITUENTS 117

based on the researches, first of Miescher and subsequently of
Hoppe - Seyler, on the. composition of pus. Pus cells, however,
are essentially composed of extravasated leucocytes which have
lost their vitality in great measure, or are on the way to dissolution.
They cannot, therefore, have the same chemical composition as
young and normal leucocytes.

Lilienfeld has recently studied the chemical composition of the
leucocytes of the lymph (lymphocytes) — which are richly distri-
buted in the reticulum of the lymphatic glands — with interesting
'results.

When a considerable quantity of lymph nodules previously
freed from fat and blood-vessels is put under pressure, a turbid
juice is yielded containing many well-preserved leucocytes, which
can be separated from the liquid by centrifuging. These readily
dissolve in water, and it is possible with magnesium sulphate to
obtain two globulins from the filtrate of the watery extract, one of
which coagulates at 73-75° C., the other, on the contrary, at 48° C.
If dilute acetic acid be added to the filtrate of the watery extract, a
phosphorus-containing substance belonging to the group of nucleo-
proteins, which Lilienfeld terms nucleo-histone, is precipitated, and
this is the principal constituent of the nucleus, not only in
leucocytes, but in other cells also.

Nucleo-histone (which can be obtained pure, in the form of a
white powder, soluble in water) breaks up, on treatment with
baryta, or with dilute hydrochloric acid, or boiling water, into its
two component groups: a nuclein, which Lilienfeld calls leuco-
nuclein, and an albuinose, which, as we have seen, was in the first
instance extracted by Kossel from the nuclei of birds' erythrocy tes,
and which he called histone.

On making an alcoholic extract from the mass of leucocytes
(obtained as above) it is found to contain protagon, lecithin,
cholesterin, inosit, and potassium phosphate. Fat is exhibited by
an ethereal extract.

Besides these substances, leucocytes contain a small, constant
amount of glycogen (Hoppe-Seyler).

According to Lilienfeld, the quantitative per cent composition
of leucocytes is as follows : —

Protein substances . . . . . . 1'76

Leuconuclein 6878

Histone 8-67

Lecithin ......... 7*51

Fat 4-02

Cholesteriii ........ 4*40

Glycogen . . . 0'80

Nuclein bases (weighed as silver compounds) . . 15*17

IX. The Blood-Platelets, which Bizzozero (1880) regarded as
the third formed element of the blood, had been previously
VOL. i I &

118 PHYSIOLOGY CHAP.

described by Hayem under the name of haematoblasts, because
they were erroneously considered to be the precursors, or early
stages of development, of the erythrocytes (Fig. 41). They are in,-
the form of circular flat discs and consist of a finely granulated, '
highly refrangible substance, colourless (hence entirely destitute of
haemoglobin), and staining fairly intensely with aniline dyes. They
are two to three times smaller than the erythrocytes (2-3 /* ; see

Fig. 41). Their number varies
% '" from 200,000 to 500,000 per
& c.nmi. The numerical relation

of the leucocytes to the plate-
: lets is about 1 : 40, and of
the platelets to the erythro-

Fio. 41.— Blood-platelets viewed from the surface CyteS about 1:25. Their Slll'-
and laterally : highly magnified. In the centre is n • r, • i i • j

an eiythrocyte for comparison of size. lace IS highly VISCOUS, and 111

stagnant blood they agglutin-
ate, forming granulated heaps which readily break up and dissolve
in the plasma.

Lowit is of opinion that the platelets are formed by disintegra-
tion of the leucocytes, and are not pre-existent in the blood before
it is extracted from the vessels. Bizzozero, however, proved that
they can easily be seen in the mesenteric vessels of guinea-pigs,
and in the wings of bats, on retarding the circulation. Osier, in
investigating the mesentery of the mouse (Fig. 42), confirmed this
observation. But the fact that they are found in living, circulating
blood does not seem a sufficient argument for regarding them
as distinct morphological and physio-
logical individuals. Lilienfeld's later Jnu-^frj mr '._*
researches proved that the platelets ^^& Q^\°'* !»$
contain nuclein in the form of nucleo- ^^l^0^0^!

albumin, the micro-chemical reactions ..-LJl^ ° s "" ° *° f~
of which are similar to those of the

nuclei Of the leUCOCyteS. It Seems not Fi««. 4-1. — Erythrocytes and blood-

improbable that they are derived from ffi±ita<S3£) ""
the latter, owing to disintegration of

, cellular protoplasm. Besides blood-platelets, the older observers
detected granules and irregular protoplasmic fragments of various
dimensions (and quite distinct from the fat drops that dissolve
in ether) in the blood, which evidently originate in the disintegra-
tion of the protoplasm of the lymphatic cells or leucocytes; on
this they founded the hypothesis that the platelets too are derived
from the disintegration of leucocytes.

In accordance with this theory, Fano has demonstrated that
there are scarcely any platelets in dog's lymph. Probably this is
due to the fact that the younger lymphatic cells predominate in
lymph, and that their protoplasm disintegrates less readily. It
should also be added that blood-platelets of characteristic form

iv THE BLOOD : FOBMED CONSTITUENTS 119

do not exist in blood that has been whipped and defibrinated, and
that they disappear from the blood of dogs that have been
repeatedly bled, with subsequent infusions of the same blood after
it has been defibrinated. In such animals nothing otherwise
abnormal can be detected, and the blood -platelets gradually
reappear, and are present in their usual number after a few days
(Gad). On the theory that the platelets originate in the
decomposition of leucocytes, the explanation of these facts may be
that the young leucocytes, supplied to the blood by the lymphatic
system, require a certain time to develop, become adult, grow old,
and disintegrate, when their nuclei give rise to the formation of
new platelets.

On the other hand, not a few of the recent workers in this
field incline from many standpoints to the view that the platelets
originate from the red corpuscles.

Kb'ppe, Hirschfeld, and Pappenheim observed that a certain
number of erythrocytes are spherical in form, without depressions,
within which are masses that stain pink with tri-acid, and faint
turquoise with methylene blue, and which when isolated differ in
no respect from blood - pla telets ; while blood - platelets can often
be distinguished among the erythrocytes. Other observers hold
that the ery throcy te consists of two parts — a central, and a peri- .
pheral stratum. The peripheral layer contains the haemoglobin
(Foa) : beneath this lies the true protoplasm.

It must also be remembered that according to Engel, every
non- nucleated blood -corpuscle has at one time or other been
one of those nucleated corpuscles of which the mantle contains
haemoglobin and is aurantiophile, its chroniatin consisting of
nuclein, and its achromatic acidophile substance containing
protein. When, under normal conditions, the nuclei of the red
nucleated corpuscles apparently disappear in kariolysis, the nuclei
lose their shape, but the chemical substances of which they are
composed persist under other forms. One form of these nuclear
rests is the basophile granulation of the erythrocytes (see below) ;
the other, more common, form is represented by the almost
amorphous blood platelets. On this theory it may be said that
every red corpuscle of the depressed form has already lost its
platelets, while erythrocytes from which the platelets are on the
point of issuing, or in which they are still confined within the
corpuscle, are the more nearly spherical.

This mode of origin of the blood-platelets would account for
the appearance they sometimes present of escaping, even where
detachment is not complete. The- body thus detached may, even
if rarely, resemble a nucleus surrounded by protoplasm.

Foa has recently (on repeating with modern methods of fixing
and staining the experiments he made in 1889, in collaboration
with Carbone) confirmed the existence of platelets in the spleen

VOL. i I c

120 PHYSIOLOGY CHAP.

which are identical with those circulating in the blood ; these, he
maintains, are not simply deposited there, but originate in situ.
According to Foa the platelets are autonomous elements, and/v
since they are composed of protoplasm and nuclear substance, are
real cells sui generis, capable of multiplying by direct division in
the circulating blood.

In view of the importance assigned to the platelets in respect
of blood coagulation, we shall return to them after considering the"
chemical constitution of blood plasma.

The microscopic examination of the blood can be made with fresh or fixed
preparations. It is essential to use slides and cover-glasses that have been
scrupulously cleaned (first in alcohol containing HC1, and then in ordinary
alcohol) and well dried with a linen cloth. The blood required is obtained
by pricking the ball of the finger or lobe of the ear with a needle (better, a
lancet), so that the blood wells out in drops without employing compression.
In order to examine fresh preparations microscopically, it is only necessary to
take up a drop of blood on the cover-glass and lay this on the slide with the
drop downwards. If the glasses are clean, the blood spreads uniformly between
them, and the preparation only needs a gentle tap on the coYer-glass to
distribute the morphological elements in an even layer and make it ready
for observation.

In order to keep the formed constituents of the blood alive for prolonged
observation, a drop of blood must be gently compressed between two cover-
glasses, which are then separated by drawing one across the other. One of
these films is laid over the central depression of a special slide, such as is used
for the observation of bacteria in hanging drops. The margin of this de-
pression is previously filled with vaseline to prevent the intrusion of air, which
would cause the preparation to dry up — making a minute moist chamber.
The preparation is then placed on Schultze's warm carrier and kept at the
required temperature.

The fixing of the blood for microscopic study is performed in two different
ways, by the wet or the dry method. To fix it by the wet method the blood
is collected in a watch-glass and the various fixing solutions added. Such are
solutions of osmic acid, corrosive sublimate, palladium chloride, Kleinenberg's
picro-sulphuric acid, Flemming's osmic - chrom - acetic mixture, etc. When
completely fixed, the solution is removed, and the preparation can be examined
immediately or after staining. Fixing by the dry method is effected by
warming the film preparation. It must be dried in the air, and then passed
6-10 times through the flame of a spirit lamp, care being taken not to scorch
it ; or it may be laid for about an hour on a copper plate, warmed to 120°.
Fixation is also effected by placing the air-dried blood film for an hour in a
mixture of equal parts of absolute alcohol and ether.

Excellent results are obtained by warming, and then dipping into alcohol
and ether.

Staining is necessary in studying the detailed structure of the formed
elements of the blood. To stain fresh preparations, weak solutions of iodine,
methyl-violet, methylene-blue, eosin, etc., must be used. For staining dry
preparations, countless methods are described in special text-books, but we
must here confine ourselves to the most ordinary, which are also the most
practical for the doctor. The film-preparations are passed 6-10 times through
the flame of a lamp, and then placed for about half-an-hour in equal parts of
absolute alcohol and ether. They are then dried again in the air, and stained
in a watch-glass with Ehrlich's acid haematoxylin (haematoxylin 2 grins.,
absolute alcohol 60 grms.). To this first solution is added the following mixture,
which has previously been saturated with alum : glycerin 60 grms., distilled

iv THE BLOOD: FORMED CONSTITUENTS 121

water 60 grms., acetic acid 3 grms. In 5-10 minutes the cover-glasses are taken
out of the haematoxylin, washed in water, and stained for the second time by
dipping them for a few moments into a 1 per cent solution of eosin. They
are then washed again in distilled water, wiped at the edges with filter-paper,
dried over the; flame, and mounted on the slide with a drop of Canada balsam
dissolved in xyloL

The nuclei and blood-platelets stain blue with the haematoxylin, .the
protoplasm pink with the eosin.

A copious literature has recently sprung up in regard to
flsmotic phenomena, and the resistance of the erythrocytes to
yielding their haemoglobin, when brought into salt solutions of
different concentrations. Since, however, this subject is intimately
•connected with the physico-chemical structure of the blood
plasma, we shall consider it in the next chapter.

The important question of the origin, formation, and
destruction of Erythrocytes and Leucocytes will be discussed in
treating of the function of the haematopoietic and haematolytic
organs.

BIBLIOGRAPHY

WELCKER. Zeitschr. f. rat. Med., 1858.

PREYER. Die Blutkrystalle. Jena, 1871.

A. ROLLETT. Hermann's Handbuch d. Physiol., 4, 1880.

•C. BIZZOZERO. Arch. It. Biol., 1882, 1883.

HAYEM. Arch, de pliysiol., 1883. Gaz. med., 1883.

HEDIN. Strass. Arch. f. Physiol., 1890.

E. A. SCHAFER and A. GAMGEE. Schafer's Text-Book of Physiology, i. 1898.
H. F. HAMBURGER. Osmotischer Druck u. lonenlehre. Wiesbaden, 1901-5.
R. HOBER. Phys. Chemie der Zelle u. der Gewebe, 2nd ed. Leipzig, 1906.

F. WEIDENREICH. Die roten Blutkbrperchen-Ergebnisse. Merkel and Bonnet,

1903-4.

•GRAWITZ. Klin. Path, des Blutes, 1902.
ENGEL. Leitfaden z. klin. Unters. des Blutes, 1902.
FOA. Arch. d. scienze med. Turin, 1906.

Recent English Literature : —

W. MYERS. The Causes of the Shape of Non-nucleated Red Blood Corpuscles.

Journ. of Anat., xxxiv. 3, p. 351.
A. GAMGEE. On the Behaviour of Oxy haemoglobin, etc., etc., in the Magnetic

Field. Proc. Roy. Soc., Ixviii. 450, p. 503.
J. HALDANE. The Colorimetric Determination of Haemoglobin. Journ. of

Physiol., 1900-1, xxvi. 497.

G. N. STEWART. The Conditions that underlie the Peculiarities in the Behaviour

of the Coloured Blood Corpuscles to certain Substances. Journ. of Physiol.,

1900-1, xxvi. 470.
5. PESKIND. Notes on the Action of Acids and Acid Salts on Blood Corpuscles

and some other Cells. Amer. Journ. of Physiol., 1903, viii. 99 and 404.
O. N. STEWART. The Behaviour of Nucleated Blood Corpuscles to certain

Haemolytic Agents. Amer. Journ. of Physiol., 1903, viii. 103.
•G. T. .KEMP. Relation of Blood Plates to the Increase in the Number of Red

Corpuscles at High Altitudes. Proc. of the Amer. Physiol. Soc. (Amer.

Journ. of Physiol.), 1902, vi. p. xi.
•G. T. KEMP and 0. 0. STANLEY. Some- New Observations on Blood Plates.

Proc. of the Amer. Physiol. Soc. (Amer. Journ. of Physiol.), 1902, vi. p. xi.
€. C. GUTHRIE. The Laking of Dried Red Blood Corpuscles. Amer. Journ. of

Physiol., 1903, viii. 441.
•G. N. STEWART. The Influence of Cold on the Action of some Haemolytic Agents.

Amer. Journ. of Physiol., 1903, ix. 72.

122 PHYSIOLOGY £HAP. iv

E. T. REICHEIIT. Quick Methods for Crystallising Oxyhaemoglobin. Amer.

Journ. of rhysiol., 1903, ix. 97.
P. B. HAWK. On the Morphological Changes in the Blood after Muscular^

Exercise. Amer. Journ. of Physiol., 1904, x. 384.
P. P. LATDLAW. Some Observations on Blood Pigments. Journ. of Physiol.,

1904, xxxi. 464.

C. E. HAM and H. BALEAN. The Effects of Acids upon Blood. Journ. of Physiol.,

1905, xxxii. 312.

S. PESKIND. Ether-laking : A Contribution to the Study of Laking Agents that

Dissolve Lecithin and Cholesterin. Amer. Journ. of Physiol., 1905, xii. 184.
C. G. DOUGLAS. A Method for the Determination of the Volume of Blood in

Animals. Journ. of Physiol., 1905-6, xxxiii. 493.
E. W. REID. Osmotic Pressure of Solutions of Haemoglobin. Journ. of Physiol.,

1905-6, xxxiii. 12.
T. W. CLARKE and W. H. HUHTLEY. On Stilph-haemoglobin. Journ. of Physiol.,

1907-8, xxxvi. 62.
H. C. Ross. On the Death of Leucocytes. Journ. of Physiol., 1908, xxxvii.

327.
H. C. Ross. On the Yacuolation of Leucocytes and the Liquefaction of their

Cytoplasm. Journ. of Physiol., 1908, xxxvii. 333.

CHAPTER V

THE BLOOD : PLASMA

CONTENTS. — 1. Different methods for separation of blood plasma from
corpuscles. 2. Histogenic substances or proteins of plasma : iibrinogen, serum
globulin, serum albumin, sero-mucoid. 3. Nitrogenous histolytic products of
plasma. 4. Fatty substances. Carbohydrates and their derivatives. 5. Inorganic
substances. Blood gases. 6. Theory of Coagulation : (a) conditions of blood
coagulation ; (b) disintegration of corpuscles as cause of coagulation ; (c)
fibrinogen as fibrin generator ; (d) analogies between blood coagulation and
curdling of milk ; (<•) importance of time in coagulation ; (/) thrombin and
nucleins as coagulating substances ; (<j] histone and cytoglobulin as anti-
coagulating substances. 7. Osmotic pressure, molecular concentration, electrical
conductivity and viscosity of blood and serum. 8. Functions of the blood : (a]
effects of bleeding ; (b) effects of transfusion of homo- and heterogeneous blood ;
(c) bactericidal and immunising properties of blood and serum. Bibliography.

I. THE property by which the blood coagulates spontaneously a
few moments after it has been drawn from the veins, and the
instability of the corpuscles, which renders them liable to injury
from the slightest causes, owing to modification of their osmotic
and secretory properties, make it difficult and almost impossible
to separate the plasma from the total mass of corpuscles, or formed
elements, in the identical amount and composition in which it
circulates in the vessels.

To effect this as perfectly as possible, horse's blood must be
employed, since this, as has been said, coagulates slowly, and gives
time for the red corpuscles (which have a higher specific gravity)
to separate partially from the plasma and sink towards the
bottom of the vessel. If the blood streaming from the veins is
cooled to about 0° C. by receiving it in a tall narrow cylindrical
vessel, surrounded with ice, coagulation can be retarded so long
that after about an hour the transparent plasma, free from
erythrocytes, and containing only a small admixture of leucocytes,
floats on the corpuscles, and can be removed with a previously
cooled pipette (Briicke). It is, however, impossible by this
method, even with all the precautions suggested by experience,
to avoid a certain diffusion of haemoglobin from the corpuscles to
the plasma, which then becomes more or less tinted and shows
the characteristic spectrum of oxyhaemoglobin.

123

124 PHYSIOLOGY CHAP.

If the plasma thus obtained by simple cooling of horse's blood
is warmed to the temperature of the atmosphere, it coagulates,
like the blood in toto, arid an incoagulable fluid separates outr
which is pure serum. If the clot is squeezed and washed out/
the purest fibrin is obtained. Serum is, therefore, nothing but
plasma in which the protein which gives rise to the formation
of fibrin, and was therefore termed fibrinogen, is wanting. Besides
this cardinal difference, however, we shall see that other secondary
differences that can be demonstrated between plasma and serum
are the result of the coagulation process.

Since the plasma of horse's blood can coagulate, it is. not
suitable for the examination of the true proteins which it normally
contains. In order to obtain a purer plasma, as free as possible
from corpuscles and haemoglobin, and at the same time incoagul-
able, the blood of a dog, into whose veins a certain quantity of
albumoses (pro-peptones) has been injected intravenously a few
minutes before the bleeding (Schmidt-Miihlheim, Albertoni, Fano),
is employed. The peptonised blood obtained in this way has lost
its faculty of spontaneous coagulation, so that it is easy by
prolonged centrifuging to separate the plasma completely from
the mass of corpuscles. The same effect is arrived at by intra-
venous injection of leech-extract (Haycraft). Apparently all
blood-sucking animals, independent of their zoological position,
and merely in relation to the nature of their food and their mode
of obtaining it, possess substances in their buccal secretions which
impede coagulation : such are the leech (Haycraft), the tick
(Sabbatani), and the mosquito (Grassi).

The plasma obtained from peptonised blood is a transparent,
light yellow fluid, absolutely free from haemoglobin ; under the
microscope it is found to contain no erythrocytes, and only a few
leucocytes and blood-platelets. It does not coagulate spontane-
ously ; but when diluted with an equal volume of water, or when
a stream of carbonic acid gas is passed through it for a couple of
minutes, it is soon converted into a quivering, gelatinous mass,
from which the serum, in which floats the snow-white cake of
pure fibrin, separates out (Fano).

Incoagulable plasma can also be obtained by receiving the
blood that issues from the veins in a vessel which contains a
certain quantity of salt solution, since, with hardly any exceptions,
all salts render the blood incoagulable in greater or less degree
owing to various physical and chemical reasons (Buglia and
Gardella). The solutions most frequently employed in the
chemical physiology of the blood are sodium sulphate, sodium
chloride, and magnesium sulphate. Twenty -four hours after
extraction, or sooner if the centrifuge is used, the mass of the
corpuscles separates from the plasma. One inconvenience of this
method is that the corpuscles are deformed, and a considerable

v THE BLOOD: PLASMA 125

amount of haemoglobin diffuses out and stains the plasma. The
separation of the proteins of the blood in a pure state was,
however, effected by A. Schmidt and Hammarsten, mainly with
salted plasma. To-day we are acquainted with various less active
saline solutions, which when properly used do not rupture the
erythrocytes, and yield a perfectly colourless plasma ; among these
are sodium oxalate and metaphosphate.

Lastly, it should be noted that plasma can be rendered in-
coagulable by adding sodium oxalate to the amount of 0*06 -0*10
per cent to the fresh blood issuing from the vein. We shall
return to these facts in discussing the theory of coagulation.

Still greater difficulties arise when we attempt not merely to
obtain more or less genuine plasma, but also to determine the
quantitative ratio between the normal mass of corpuscles and the
plasma. The methods employed with this object by Hoppe-Seyler
and Bunge give very different values, not only for different
animals, but also for different animals of the same species. With-
out citing the results of the various series of observations, we may
say that in man the amount of plasma is slightly in excess of
that of the corpuscles, in the wet state : average, 52 per cent
plasma and 48 per cent corpuscles (Arronet). In the horse, on
the contrary, the opposite result is obtained : average, 47 per cent
plasma and 53 per cent corpuscles (Bunge).

II. According to recent analysis, blood plasma contains on an
average 9T8 per cent water and 8'2 per cent solid substances;
6 '9 per cent of this consists of proteins, so that all the other
constituents of plasma are reduced to I'S.per cent, of which about
0*46 per cent are organic extractives, 0*84 per cent inorganic.

In all the higher animals the proteins of blood plasma consist
mainly of globulins (metaglobulin and paraglobulin), and to a
less degree of serum albumin.

The most important is metaglobulin, commonly called fibrino-
gen, because it gives rise during coagulation to fibrin formation.
It is therefore entirely absent from serum, and to prepare it in a
pure state salted plasma must be used, or the morbid transudations
of the pericardium (hydropericardial fluid), or the tunica vaginalis
testis (hydrocele fluid), which always contain it. It can be separated
out from salted plasma by utilising the property which causes
fibrinogen to precipitate from its solutions so soon as these
contain 16 per cent of sodium chloride, when none of the other
globulins have lost their solubility, since they are precipitated
only when their solutions are saturated with sodium chloride.
To precipitate metaglobulin from, the transudates, it is only
necessary to add sodium chloride in the solid form.

If a solution of pure fibrinogen is warmed to 56-60° C., it
splits up into two other globulins, of which we shall speak later,
and an insoluble coagulum is formed.

126 PHYSIOLOGY CHAP.

Paraglobulin is also known as serum globulin, because it
remains unchanged in the serum after spontaneous blood coagula-
tion. It can be readily separated in the pure state by diluting
the serum with at least ten volumes of water, and then leading a
stream of carbonic acid through it, or by slightly acidifying it with
dilute acetic acid, or by saturating it with magnesium sulphate.

Serum globulin dissolved in a 10 per cent solution of common
salt coagulates at 75° C.

Serum albumin or serin is separated from globulins of the
serum by salting the latter with magnesium sulphate at 30° C.,
filtering it at the same temperature, and adding to the saturated
filtrate dilute acetic acid, or ammonium, or sodium sulphate to
saturation. This precipitates the serum albumin : the precipitate
is separated by centrifuging, and purified by dialysis.

Pure serum albumin dissolved in distilled water coagulates
rapidly at about 50° C. ; but on adding salts its heat-coagulability
is considerably lowered. In solutions of 5 per cent sodium
chloride, coagulation first occurs at 72-75° C.

Serum albumin is not identical with ov-albumin, 'as appears
from certain chemical properties, and more particularly from the
physiological characteristic by which the latter, when injected into
the veins, is not retained in the blood, but is at once excreted by
the kidneys and passes unchanged into the urine.

After Morner had isolated a protein of the m.ucinoid group
from white of egg, to which he gave the name of ovo-mucoid,
Zanetti, in Ciamician's laboratory, by a happy inspiration sought
to ascertain whether the same or some other analogous sub-
stance were not also contained in blood serum, which shows a
certain similarity to egg-white in its composition. His experiments
with ox serum were crowned with success. The new substance
sero-mucoid, which he discovered, exhibits physical and chemical
properties highly similar to those of ovo-mucoid.

The four proteins named above are all that have at present
been definitely demonstrated in blood plasma. When exposed to
the action of freely diluted acids or alkalies, and warmed, they
turn into alkaline or acid albumins, the former being similar to
the casein of milk, the latter to syntonin. But there is no
evidence for the presence of these in normal blood plasma.

The quantitative relation between fibrinogen, serum globulin,
and serum albumin is not easy to determine. It appears probable
that the relative quantity of these three proteins is very variable,
and that all three function as tissue-forming substances, the
albumin representing the true form, and the two globulins two
different modifications produced by cell metabolism. Miescher
and Burckhardt have actually shown that the globulins of the
blood increase during hunger, while the albumin decreases.

The same facts and the explanation of them have been

v THE BLOOD: PLASMA 127

confirmed by many experiments carried out by Fano and his pupils
Ducceschi and di Frassineto, who studied the blood in anaemia, in
the two sexes, after thyroidectomy, etc.

The serum of mammalian blood contains a saccharifying
ferment, as was pointed out by Magendie, Cl. Bernard and others.
Bial found that the blood of man (obtained by bleeding, or taken
from the placenta) also contained the power, although in a lesser
degree, of converting starch paste into glucose and dextrin, and is
further capable of converting maltose into dextrose. In the new-
born, in man as in other animals, the saccharifying property is
very low, and may be entirely absent ; it increases with age, and
with its increase there is an apparent diminution in the glycogen-
content of the muscles.

E. Cavazzani found that the quantity of haemo-diastase is not
alike throughout the vascular system ; the blood of the portal
veins contains more than the blood of the hepatic veins, the
jugulars, and the carotid arteries. This leads to the conjecture •
that it originates in the digestive organs, and that its presence in
the blood is to a certain extent fortuitous, and dependent on
digestive processes.

According to recent researches, blood serum contains various
other enzymes.

Claude Bernard (in his observations on the amount of glycogen
in normal dog's blood) found it necessary to test for glycogen
immediately after the blood had been drawTu from the vessels of the
animal, because in a longer or shorter period, according to the sur-
rounding temperature, it was destroyed by a fermentative process.

A similar disappearance of glycogen (as also of laevulose,
maltose, and galactose) occurs on adding sugar artificially to the
blood in vitro, and it was more particularly after the researches of
Lepine and Barral that this disappearance of sugar in the blood
was attributed to the action of a special glycolytic enzyme, which,
according to these authors, originated in the white corpuscles.
This glycolysis is effected, according to Nasse, Eohmann and
others, by an oxidative process, and more precisely by the agency
of an oxidising ferment (oxidase), while according to Stoklasa it is
due to a process analogous to alcoholic fermentation, to trie agency,
that is, of a special zymase.

In addition to these two amylo- and glycolytic enzymes there
exists in the serum, according to Hanriot, a lipolytic ferment
(lipase), which, according to most authors, acts only on inono-
butyrin, and is incapable of splitting up olein and other neutral
fats (Arthus, Doyen and others). >

Along with this restricted lipolytic property of serum, the
blood, according to Connstein and Michaelis and Weigert, has also C
a property of transforming fats into certain soluble substances, the
composition of which is not known.

128 PHYSIOLOGY CHAP.

Nor does this complete the enumeration of all the enzymes in
blood. According to the most recent researches, it further
contains oxidases, catalases, and proteolytic enzymes (chymosin
and trypsin) ; nor are the corresponding anti-enzymes or anti-
ferments lacking; according to Delezenne there is also an anti-
kinase.

Quantitative Estimation of Fibrinoyen. — The quantitative estimation of the
fibrinogen or metaglobulin of salted plasma, which also contains paraglobulin,
is based on the different solubilities of these two substances in salt solu-
tions. Hammarsten (Pflugers Arch, xvii., xviii., xix.) has shown that para-
globulin remains in solution in water containing 16-18 per cent NaCl, while
fibrinogen, on the contrary, is completely precipitated, and remains soluble
only at a lower concentration. If a sufficient quantity of saturated salt
solution is added to a vessel containing salted plasma, a flocculent precipitate
of fibrinogen is obtained on stirring the fluid briskly with a glass rod. In
order to purify this, it is again dissolved, after filtering, in an 8 per cent
solution of NaCl, and reprecipitated with concentrated solution as before.
This operation is repeated three or four times, and the last precipitate, which
is quite white, and held in a filter previously dried at 115'J C., and weighed,
is placed in a warm chamber at 115° C. to coagulate. The filter is then
replaced on the. stand ; the coagulated fibrinogen is washed with warm water,
to remove the salts, and then with alcohol and ether. The filter and precipi-
tate are then dried again, and weighed repeatedly at long intervals, till a
constant weight is obtained. It is now easy from the known quantity of
blood employed to calculate the fibrinogen content of 100 or 1000 c.c.

Estimation of Fibrin Ferment. — Carbone's is the only known method of
estimating the fibrin ferment contained in blood-serum ; it yields compara-
tive, not absolute results. This method is based on the fact that leech
extract acts in regard to the ferment in a manner analogous to that of anti-
toxin towards toxin. Carbone mixed a constant quantity of fibrinogen
dissolved in 0*8 per cent NaCl, in a series of test-tubes, with a constant
quantity of the serum in which the ferment was to be titrated. He then
added to the different test-tubes an increasing quantity of leech extract, and
eventually made the volume of liquid equal in all by adding 0'8 per cent
NaCl. After twenty-four to forty-eight hours he examined the test-tubes
and the clot, which only formed where there was little leech extract. He
estimated the quantity of ferment by the quantity of extract necessary to
neutralise its coagulating action.

Estimation of Paraglobulin. — Magnesium sulphate is added to saturation
to a measured quantity of blood serum. The fluid is vigorously shaken, the
precipitate in the form of a white paste, finely granulated, is collected on a
filter and washed with saturated solution of MgSO4, to remove the albumin.
If the precipitate left on the filter is coloured, it is dissolved in a dilute
solution of MgSO4 or NaCl, and reprecipitated as before. This operation is
repeated several times, and then completed in the manner described for the
estimation of fibrinogen.

Estimation of Serum Albumin. — The serum saturated with magnesium
sulphate, from which the paraglobulin has been removed by filtering, can be
used again for the quantitative estimation of serum albumin. This can be
precipitated by the addition of a small amount of 0*5- 1 per cent of acetic
acid. To purify it, dissolve again in water, and reprecipitate with solution
of ammonium sulphate. The further treatment is the same as that described
above for fibrinogen. Serin is, however, more frequently calculated by
difference, as follows : — In one portion of serum the paraglobulin is
estimated by the preceding method, and in a second portion, equal to the

v THE BLOOD : PLASMA 129

first, the total weight of the proteins coagulated by alcohol or by heat. The
percentage amount of serum albumin can be calculated from the difference
t>etweeii the two values.

Estimation of Sero-mucoid. — I. To prepare and simultaneously estimate
sero-mucoid, Zanetti used the same method Morner employed for ovo-mucoid.
The proteins are first precipitated from a given amount of blood serum
diluted witli two volumes of 10 per cent NaCl solution, by coagulation, after
previous acidification with acetic acid. The filtrate is evaporated on the
water bath to a reduced volume, and is then treated with alcohol. To
purify the precipitate obtained, which consists of sero-mucoid, it is again
dissolved in water, and reprecipitated with alcohol. This operation is
repeated five or six times, till a very slightly coloured precipitate is obtained,,
which can be collected on a filter that has been previously dried and
weighed. After repeated washing with ether, the substance is dried in vacuo
over sulphuric acid till the weight is constant. The sero-mucoid appears as
a light straw-coloured powder. It is somewhat hygroscopic, dissolves in
warm water, and gives all the reactions of mucoid substances. Its property
of reducing Fehling's solution after previous boiling with hydrochloric acid,,
led Zanetti to term it gluco-protein.

III. The various proteins differ little in their percentage com-
position, and are probably derived from the molecular complex
into which the different nuclei or groups of atoms have entered
in different relations. In fact, when broken up by steam at high
pressure, or by prolonged boiling with dilute alkali or mineral
acids, they invariably yield the same products, viz. ammonia,
hydrogen sulphide, and a series of ammo-acids, among which
tyrosine, leucine, and asparaginic acid are always present. Since
tyrosine is a compound of the aromatic series, and leucine and
asparaginic acid are two bodies of the fatty series, we may conclude
that atomic groups of both series enter into the protein molecule.

Within the body, however, in consequence of the metabolic
activity of the living elements of the tissues, the proteins give
rise to a large number of decomposition products, which are
either simple waste products, destined as such to be eliminated
by the various excretory organs, or products of internal secretion,
destined to fulfil other functions and to undergo further trans-
formations before they are eliminated. For the most part these-
consist of the constituents of urine, which are excreted by the
kidneys, among the most important being creatine, creatinine, uric
acid, hippuric acid, carbamic acid, and urea. All these are nitro-
genous compounds, and are therefore derived from retrogressive
or katabolic metamorphoses of the proteins.

As these waste products are promptly eliminated as fast as
they reach the blood plasma, they can obviously exist there only
in very minute quantities. As a matter of fact, urea and
ammonia are the sole constituents of urine that can be isolated
from blood serum, urea only in an amount of which the maximum
does not exceed O05 per cent (I. Munk), ammonia in an average
amount of O79 mgrni. to each 100 grins, of blood (Beccari). Creatine
and uric acid are found in much smaller quantities; hippuric

VOL. I K

130 PHYSIOLOGY CHAP.

acid least of all, since, as will be shown later on, the greater part
at any rate is formed by a synthetic process in the kidneys.
Under pathological conditions, however, when the renal function,
is profoundly affected or abolished (uraemia), as also in grave''
alterations of the blood (leucaemia), besides these nitrogenous
products others, which are normally present in the urine in
exceedingly small quantities, e.g. the xanthine bases (Scherer), can
be demonstrated in the serum.

IV. Besides the nitrogenous compounds, neutral fats are found
in the blood serum, emulsified to minute drops which can readily
be extracted with ether. The amount, which under normal con-
ditions does not exceed Q'l-0'2 per cent, increases conspicuously
after a fatty meal, giving a milky appearance to the serum, and
it may reach or exceed 1 per cent of the total quantity of blood
(Kohrig) ; whereas in the fasting state only minute traces remain
(Pfeiffer). It is thus obvious that the fats of the blood are derived
principally from the fatty substances taken in with the food. In
certain morbid conditions, however (alcoholism, diabetes, diseases
of the bone marrow), the amount of fat in the blood plasma may
increase so much that the serum assumes a milky aspect (lipaemia)
as after a meal that has been rich in fats. It is therefore probable
that the fat of the blood is, even under normal conditions, derived
to a lesser extent from what is eliminated or liquefied from the
adipose tissues.

In addition to neutral fats, blood serum contains soaps,
lecithin, and cholesterin (Hoppe-Seyler). These form part of the
products of pancreatic digestion, hence they also come in part
from the digestive canal.

A third group of organic substances also found in serum are
conventionally comprised under the term carbohydrates : glucose,
glycqgen, lactic acid. There is yet another reducing substance,
which is not fermentable ; it contains phosphorus, is capable of
extraction with ether, and gives all the reactions of jecorin
(Jacobson). Lastly, there is a small quantity of animal gum
(Freund).

The most important of all these substances is certainly glucose,
which originates partly direct from the food, partly from the
digestive transformation of alimentary starch, partly from the
glycogen of the liver and muscles. The quantity of glucose in
the blood is independent of the nature of the food, because, as we
shall see later, nearly all the glucose absorbed from the intestine
is stored up in the liver in the form of glycogen (liver starch).
The amount of glucose found in normal human blood varies from
O'lO to 0'15 per cent (Otto); but under abnormal conditions it
may reach 0'3 per cent or more. It is at a maximum during post-
digestive absorption in the blood of the portal veins, while during
inanition it is most abundant in the blood of the hepatic veins.

THE BLOOD: PLASMA

131

The small amount of glycogen that can be demonstrated in
blood serum (Pavy) probably derives from the disintegration
of the leucocytes, which, as stated, contain a certain amount
of it.

The constant presence of lactic acid in blood serum is in-
dependent of the ingestion of carbohydrates, while it is, on the
contrary, partly dependent on the flesh food. The amount of
lactic acid found in the blood of dogs during absorption after a
full meat meal, may amount to Q'3-0'5 per cent, while after
forty-eight hours' starvation it diminishes to 017 per cent
(Gaglio). Lactic acid, as we shall see, is one of the decomposition
products of proteins, elaborated either by the blood corpuscles or
by the living elements of the various tissues.

V. The mineral constituents of blood plasma occur partly in
the form of free salts, partly in combination witli the proteins,
from which they cannot be separated by simple dialysis.
What the true physical and chemical conditions within the
plasma — the reciprocal relations and the fixed or labile bonds
between the various mineral constituents on the one hand, and
the various proteins on the other — may be, is one of the most
difficult problems in the chemical physiology of to-day, and its
solution is the aim of various physico-chemical researches, of
which this is not the place to speak.

If combustion is employed to isolate the inorganic matters
from the dry residue of serum, the ash- will be found to contain
a large amount of sulphates, derived from the combustion of the
sulphur of the proteins, which are not among the mineral con-
stituents of true plasma. In the same way, if care be not taken
before the serum is incinerated to remove the lecithin by ether,
there will, owing to combustion of its phosphates, be an excessive
increase in the phosphates of the ash.

Setting aside for these reasons the sulphates and phosphates
found in the ash of serum, the results of the different analyses
made for man and for the other mammals harmonise perfectly for
the rest of the constituents, as appears from the following table : —

In 1000 parts of si'runi.

Human Blood
(C. Schmidt).

Pig's Blood
(Bunge).

Calf's Blood
(Bunge).

Average of the
three analyses.

K20 .

Na20
Cl .
CaO .
MgO.

0-394
4-290
3-612
0-155

0-101

0-273
4-272
3-611
'0-136
0-038

0-234
4-351
3-717
0-126
0-045

0-300
4-304
3 -646
0-139
0-061

8-552

8-330

8-473

8-450

132 PHYSIOLOGY CHAP,

These figures show that sodium chloride is by far the most
abundant constituent of the ash of serum. It is held in simple
solution in the plasma or in the form of highly unstable compounds,,,
for when serum is dialysed in distilled water, osmotic equilibrium
between the two fluids is soon arrived at in regard to the chlorine.

The greater part of the sodium of the ash exists in the form of
bicarbonate (Giirber) in the plasma, a lesser amount being com-
bined with phosphoric acid in the form of di-sodic phosphate.

It should be noted that potassium salts predominate in the
corpuscles, sodium salts in the plasma.

The osmotic pressure of plasma depends largely upon the sum
of the inorganic matters which it contains ; it is, as we shall see,
of great importance in the metabolic exchanges between corpuscles-
and plasma, and between plasma and tissues.

The blood gases, as a whole, represent a very small part of the
weight of the blood (0'10-0'15 per cent). They are oxygen, carbonic
acid, nitrogen, and also argon. The two first occur principally in
combination, the two last in simple solutions. Nitrogen and argon
are not known to fulfil any function in the animal economy ; on
the other hand (as we shall find in discussing the Chemistry of
Kespiration), oxygen and carbonic acid are of capital importance.
Here we must confine ourselves to stating that the combinations-
winch they form of oxygen with haemoglobin, and of carbonic acid
with haemoglobin and the alkalies, are very unstable, so that it ia
possible with the vacuum to separate and estimate volumetrically
the whole of the gases contained in the blood.

VI. After ascertaining the several constituents of the blood
corpuscles and blood plasma, it is easier to marshal the data
referring to the solution of the problem of Blood Coagulation, a
problem which is indeed one of the most difficult in physiological
chemistry.

Although this problem has of late years been treated with
extraordinary acumen by a number of observers (e.g. A. Schmidt
in particular), we cannot at present claim to have established
any theory that is universally acceptable in all its details.

In studying the phenomena of coagulation it is well to treat
the different questions and problems involved as if each were
separate and distinct in itself.

(a) The first problem that presents itself is why, i.e. under
what conditions, the blood, which remains fluid so long as it
circulates within the vessels, coagulates spontaneously soon after it
leaves them. This question was attacked by Hewson in the
eighteenth century, while Briicke solved it more completely in
1857.

Clotting does not depend upon the cooling of the blood, for
when frozen before coagulation, it is found on thawing still to be
fluid, and clots soon after in the usual manner. Cooling, therefore.

v THE BLOOD: PLASMA 133

retards coagulation ; as shown by the fact that when the shed
blood is warmed to the ordinary temperature of the animal
(3T-380 C.) it clots more rapidly (Hewson).

Coagulation does not depend on the quiescence of the blood
drawn from the vein, for some of the blood in the dog's heart
13 hours after death (Hewson), and the whole of a dog's blood
6J-7J hours after death by asphyxia, is found to be fluid.
Again, the blood in a tortoise heart that has been ligatured or
excised, and kept at a temperature of approximately zero, is found
to be fluid 7-8 days after (Brlicke).

Nor, again, does coagulation depend on contact with the air or
its oxygen, for the blood received under a bell-jar filled with
mercury coagulates, and the blood of a tortoise does not clot after
injection of a considerable quantity of air into its vessels (Briicke).

Contact with the normal, living walls of the vessels inhibits
coagulation of the circulating blood, while the injury or death of
the vascular endotheliuni, or the introduction of any foreign body
into the vessels (e.g. a needle pushed through the heart of a living
tortoise), make the blood coagulate (Briicke).

When the blood is received directly into a vessel greased
with vaselin, or under oil, it neither adheres to it nor clots, nor
does it on stirring with a well-greased glass rod. On the other
hand, it coagulates readily when stirred with a rod that has
not been greased, or when any foreign body is introduced which
the blood can adhere to. It is therefore" highly probable that the
circulating blood remains fluid because its morphological elements
d.o not adhere to the normal endotheliuni of the vessels, and that
a thrombus is formed whenever such adhesion becomes possible
by degeneration of the endotheliuni (Durante) or other morbid
lesions of the internal walls of the vessels and heart, as, e.g.,
in phlebitis, endocarditis, endarteritis, atheromatosis (Freund,
1886).

(&) The second question to be solved is the determination of
the immediate cause of coagulation, i.e. why the simple adhesion
of certain elements of the blood to foreign bodies, or to the injured
endotheliuni, should give rise to the formation of fibrin.

In this connection we have a series of striking observations,
which show plainly that the formation of the fibrin clot is intimately
bound up with the functional alteration or destruction of the
formed elements of the blood, more particularly of the leucocytes,
which, as we have seen, are very unstable, and easily damaged by
every imaginable external physical influence. Simple contact with
foreign bodies, to which they may adhere, is sufficient to provoke
secretion in the plasma of substances able to produce clotting.

This theory, proposed by Addisoii (1841) and Beale (1864), was
clearly demonstrated for the first time by Mantegazza (1876).
Wherever a thrombus is produced within the vessels or the heart,

134 PHYSIOLOGY CHAP,

the fibrinous clot is seen under the microscope to be infiltrated
with more or less altered leucocytes.

If a silk thread is introduced into the interior of a large vein/
and carefully drawn out after some time and investigated under
the microscope, a fine coagulum will be seen to have formed round
the thread, which is denser in the places where the leucocytes
enclosed among the filaments are most numerous (Mantegazza).

When the coagulation of a small drop of blood plasma i&
watched under the microscope, the fibrin threads of which it is
constituted are often seen to spread out like rays from a centre,
which is formed by a leucocyte or a collection of disintegrated
platelets (Eanvier, Hayem, Bizzozero).

On separating the plasma of horse's blood by cooling, and
filtering it through a triple layer of filter-paper, it can be obtained
entirely free of formed elements. In this case it will be seen that
the plasma left at the temperature of the environment may remain
fluid even after twenty-four hours. But if even a nominal amount
of a watery extract of leucocytes, or a little blood serum containing
leucocytes, be added, clotting at once occurs (A. Schmidt).

Certain morbid pathological transudations behave exactly like
the cell-free plasma, e.g. hydrocele, or pericardial fluid, which are
free from formed constituents, and are of a similar composition to
plasma. Left to themselves, they remain fluid for an unlimited
time, but coagulate so soon as a little blood clot or serum is added
(Buchanan, 1835).

When entirely freed from corpuscles by prolonged and
energetic centrifuging, the plasma separated from peptonised
blood not only does not coagulate spontaneously, but will not do
so on the addition of water, or when a stream of carbonic acid is
passed through, as is the case with peptonised plasma not wholly
deprived of leucocytes. But if a little clump of leucocytes and
platelets obtained by centrifuging be added, coagulation at once
occurs (Fano).

The theory of Hayem and Bizzozero to the effect that coagula-
tion depends essentially on injury or destruction of the blood-
' platelets, does not contradict the preceding theory, by which it is
associated with the injury or destruction of leucocytes. Assuming
(as seems probable from the researches of Lilienfeld, referred to in the
last chapter) that blood-platelets are derived from leucocytes and
represent the mass of their nuclei, the two points of view are quite
in harmony, and may be combined and enlarged into a single theory.
A. Petrone has recently discovered that the blood coagulates
firmly and rapidly in the early stages of pyrogallic acid poisoning
(1 per cent solution introduced per rectum for dogs and rabbits),
while the platelets are not injured, and even appear to increase,
the erythrocytes only suffering marked deterioration. The
analytical investigation of this complex intoxication has, however,

v THE BLOOD: PLASMA 135

been too incomplete to make it the basis of a theory so opposed to
observations and experiments conducted on simpler and, therefore,
more convincing lines. Lymph contains neither erythrocytes nor
platelets, as shown by Fano, and yet it coagulates.

(c) The third point in the theory of coagulation is to determine
on which or what chemical constituents of the blood the formation
of fibrin depends, since it is insoluble and cannot, therefore, pre-
exist as such in the blood.

It was pointed out by Hewson (1770) and by G. Miiller (1832)
that the mother-substance of fibrin is derived, not from the
corpuscles, but from the constituents of the blood plasma. Hewson
was the first to obtain salted plasma comparatively free from
corpuscles, and noted that it formed a white clot on the simple
addition of water. Joh. Miiller succeeded in filtering frog's blood,
in which coagulation had been retarded with a sugar solution,
thus separating the corpuscles that remained on the filter from the
colourless plasma of the filtrate, and obtained in the latter a clot of
pure fibrin. The first, however, to demonstrate that coagulation
is a change of chemical state in a substance of the plasma which
he termed fibrinogen (which is found isolated in the transudates
already referred to, and mixed with serum globulin and serum
albumin in the plasma), was A. Schmidt.

He assumed that two elements enter into the composition of
fibrin : fibrinogen (the fibrinogenic substance), and paraglolulin
(fibrinoplastic substance), explaining by' this the observations of
Buchanan, as cited above. Subsequently, however, it was shown
by Hammarsten (1875), and confirmed by others, that paraglobulin
takes no part in the formation of the clot, since the blood contains
an equal amount both before and after coagulation, and since a
solution of pure fibrinogen obtained from salt plasma can yield a
fibrinous clot 011 adding a little watery extract of serum, which is
quite free from paraglobulin.

(d} A fourth problem : granted that fibrinogen is able to produce
fibrin by a change in its chemical state, it must be determined in
what this change consists.

This question is attacked in the later work of Hammarsten,
Arthus, Lilienfeld, Car bone and others.

Some hold the coagulation of blood to be a phenomenon analogous
to the curdling of milk. The substance derived from the corpuscles
which excites coagulation splits up the fibrinogen into two new
globulins — thrombosin, which is insoluble, and changes into fibrin :
and fibrinoglobulin, which remains in solution in the plasma.
During this splitting of the fibrinogen, i.e. hydration, the chemical
association of water with the proteins occurs. A. Schmidt
has recently shown that pure horse's plasma, dried before coagula-
tion, weighs about 2 per cent less than an equal amount of the
same plasma dried after coagulation.

136 PHYSIOLOGY CHAP.

The presence of a certain amount of soluble and readily
ionisable lime salts in the plasma seems essential to coagulation, or
to the transformation of the soluble thrombosin into fibrin, which
precipitates as a clot. The reason why oxalates and sodium
fluoride, even in small doses, render plasma incoagulable lies in the
fact that they precipitate the calcium salts dissolved in the plasma,
and thus hinder the conversion of thrombosin into fibrin by
combination with the lime salts. Fibrin accordingly would be a
compound of calcium with thrombosin, and comparable as such
with the soluble curd which is a calcium compound of paracasein.
Just as milk casein splits under the action of the rennet ferment
into paracasein and a special albumose, so fibrinogen splits up
during blood coagulation, two-thirds of it forming thrombosin and
one-third fibrinoglobulin. As paracasein in combination with lime
forms curd, so thrombosin in the same combination produces
fibrin (Arthus, Lilienfeld).

To this ingenious parallel between the clotting of blood and
that of milk, the objection has been raised that even if fibrin
always contains lime, it is no richer in lime than is the fibrinogen ;
hence it cannot be assumed that fibrinogen takes up lime from the
plasma in its transformations into fibrin.

Others on the contrary affirm, perhaps more reasonably, that
coagulation is produced by a simple splitting of the fibrinogen into
a less soluble body that precipitates (fibrin), and another that is
soluble (fibrin globulin) which remains in the serum ; the presence
of lime seems indispensable, not to this reaction directly, but to the
production or the activity of the fibrin ferment.

In any case it is undeniable that the presence of calcium in
plasma is essential to coagulation, even if its precise action is still
undetermined.

(e) Another question to be solved relates to the chemical form
of the calcium when it participates as an indispensable factor in
coagulation.

Some hold that it intervenes as a phosphate, more correctly as a
tricalcic phosphate, and think that as it is insoluble in water, it
remains dissolved in the plasma in combination with the proteins ;
Arthus, however, demonstrated that insoluble lime salts are useless,
and that the presence of soluble salts is essential. Sabbatani
further demonstrated that it is not merely the soluble salts, but
also the ionisable salts of calcium that are always present in plasma,
which are indispensable.

It therefore appears probable that calcium intervenes in
coagulation in virtue of its characters and chemical properties as a
kat-ion, combining with those elements that have the function of
an-ions, perhaps with the leuconuclein of Lilienfeld, which we
shall discuss later.

The quantity of calcium ions adequate to produce blood

v THE BLOOD: PLASMA 137

coagulation, unlike that required in milk coagulation, is minimal,
but under uniform experimental conditions it is constant ; we thus
have a critical value for the concentration of Ca-ions, below which
the blood remains indefinitely liquid.

On the one hand, accordingly, all physical or chemical agents
that lower the concentration of the Ca-ions of the blood below the
critical value provoke incoagulability ; on the other, all those
agents which raise it above the said value favour coagulation.
Among the former are cold, high molecular concentration, small
doses of reagents which form almost insoluble salts with calcium
(oxalates, fluorides, soaps, carbonates, alkaline pyrophosphates),
moderate doses of reagents which with lime form simple salts that
are sparingly soluble (di-sodic sulphate and phosphate, sodium
bicarbonate), small doses of reagents winch with lime form
compounds that are little ionisable (tri-sodic citrate, sodic meta-
phosphate) ; among the latter are heat, dilution with water, addition
of small quantities of ionisable lime salts, addition of reagents that
liberate the calcium from its insoluble or little dissociable compounds.

On the other hand, the addition of small quantities of calcium
to normal blood invariably diminishes coagulability (Sabbatani,
Eegoli), and it was only the inexact interpretation of certain
experiments of Dastre and Hammarsten that led people for some
time to believe that it was increased by the same ; the addition
of a moderate quantity much delays coagulation : large doses
entirely prevent it (Home).

From all these results it appears, in regard to the concentration
of Ca-ions in the blood, that we must assume an optimum value
for coagulation (lying between the limits of the physiological
Variations which calcium presents in normal blood), and two
critical values, minimal and maximal, above and below which the
blood no longer coagulates.

The addition of lime increases coagulation only when the blood
is deficient in it.

(/) Next conies the question of determining by what process
the injury or dissociation of blood corpuscles leads to the breaking-
up of fibrinogen into fibrin and fibrin-globulin.

A. Schmidt and his school (Dorpat) treat blood coagulation as a
process determined by an enzyme which they call thrombin, which is
derived from the blood corpuscles, particularly from the leucocytes
and platelets. In the normal state these contain, not the ferment,
but a zymogenic substance, pro-thrombin, which on injury or
destruction of the corpuscles gives rise to the ferment proper,
tkrombin. This can be extracted either from defibrinated blood or
from blood serum, by absolute alcohol, which precipitates the
protein matters with the ferment. The ferment can be extracted
from the mass of the well-dried and pulverised clot by making a
watery extract.

138 PHYSIOLOGY CHAP.

The watery extract containing thrombin quickly produces
fibrinous coagulation, either from solutions of pure fibrinogen,
containing a small amount of lime salts in solution, or from the'
fluid transudate of hydrocele. When injected rapidly in moderate
doses into the vascular system of an animal, instantaneous death
may be produced by diffused thrombosis, which inhibits the circula-
tion of the blood (Edelberg).

That there is in circulating blood no thrombin proper, but
only pro-thrombin, is proved by the fact that the watery extract
has no coagulative action when it is obtained (as above) not from
defibrinated blood or serum, but from fresh blood received direct
from the vein into absolute alcohol (Jakowicki). The perfect
ferment, or thrombin, is only formed when the blood-corpuscles
have been injured or disintegrated.

Thrombin in a watery solution is not attacked by antiseptics ;
on warming to 75° C. it loses all its enzyme action ; it exhibits
the general properties of the globulins, and is a phosphorus-free
protein.

Thrombin is not, however, the only substance derived from
leucocytes which is able to determine coagulation by the trans-
formation of fibrin. Besides these enzymes there are other
substances (particularly in the nuclei of leucocytes and the proto-
plasm of blood-platelets) which can produce the same effect, as has
recently been established by the experiments of Lilienfeld.

We have seen that the fundamental substance of the nuclei of
leucocytes is a highly complex structure, which is termed nucleo-
histone because it results from the association of two groups, one an
acid phosphorus containing leuconuclein, the other basic, with the
properties of albumoses. Now Lilienfeld has demonstrated that
not only leuconuclein but also its derivative, nucleic acid, are
capable of decomposing fibrinogen and of producing fibrinous
clotting under all conditions in which Schmidt's thrombin has the
same action. Hist one, on the other hand, not only does not excite
clotting, but, like other albumoses, has anti-coagulative properties,
both for circulating and for shed blood.

From the blood that is rendered incoagulable by histone it is
possible to separate a histonised plasma that is highly resistant,
and only coagulates on the addition of nucleic substances. The
an ti- coagulating substance obtained by A. Schmidt from the
alcoholic extract of lymph glands, which he called cytoglobulin,
corresponds essentially with histone.

Lilienfeld's results thus tend to prove that coagulation can
occur without [fibrin ferment, through the action of the nuclein
substances of the leucocytes and platelets ; yet, as Carbone shows,
there is a considerable analogy in respect to the production of
fibrin ferment between the theory of Schmidt and that of
Lilienfeld.

v THE BLOOD: PLASMA

According to Schmidt, we have a zyniogen, pro-throinbin,
which in splitting gives rise to the ferment and to a substance,
the nature of which he does not define, which arrests the splitting
of the pro-thrombin ; according to Lilienfeld, we have nucleo-
histone, which divides into leuconuclein with a coagulating action,
and histone with an anti-coagulating action. It seems probable
enough, one may almost say certain, from the researches of
Pekelharing, that the ferment and the zyrnogen are nucleo-
proteins. Finally, according to Schmidt, the pro-thrombin is
transformed into thrombin (ferment) solely by the action of
unknown substances which he terms zymoplastic ; according to
Pekelharing zymogen is transformed into ferment solely by the
action of lime salts, and Lilienfeld's leuconuclein becomes active
as a ferment only in the presence of calcium.

To sum up, it is admitted that the exciting agent of coagulation
(fibrin-ferment, thrombin) is a derivative of nucleohistone, a
derivative of acid character, which becomes active solely in the
presence of calcium-ions ; we may therefore represent the formation
of the ferment by the following scheme : —

Nucleohistone
(paralyses the coagulating action of leuconuclein)

Leuconuclein. Histone.

(In presence of Ca-ions becomes (Arrests splitting of nucleoliistone

a coagulating ferment.) and paralyses action of leuco-

nuclein.)

The predominance of one or other of these three substances gives
rise to various normal or abnormal states of the blood, which can
be tested after the injection of albumose, or substances with
similar action.

The latest researches of Morawitz and others have led to a
more exact acquaintance with the so-called zymoplastic substances,
i.e. substances capable of accelerating the process of coagulation.
Delezenne had already observed with birds' plasma that various
extracts of organs or tissues have a similar action. Morawitz
has indicated the active principle of these extracts by the
name of thrombo-kinase, which he considers indispensable, in
addition to the calcium salts, for the transformation of pro-
thrombin into thrombin. The production of thrombokinase is
thus a general property of protoplasm, while more particularly
characterising the leucocytes of birds and the blood-platelets of
mammals.

(#) Lastly, one further question has to be explained. As
under normal conditions the old blood -corpuscles are continually
breaking up, and young, new cells substituted for those which

140 PHYSIOLOGY CHAP.

perish, how is it that thrombosis does not occur in circulating
blood, since both fibrin ferment and coagulative nucleic substances
must be poured into the plasma on the disintegration of the
corpuscles ?

This question has not at present been adequately considered.

Fano, on the strength of certain ingenious experiments,
suggested that peptonised blood does not coagulate because it
contains an anti-coagulating substance of uncertain nature, which
comes, not from the formed elements of the blood, but from the
other tissues — seeing that the addition of peptone to freshly-drawn
blood does not inhibit its coagulation. A. Schmidt, in pursuance
of this theory, subsequently extracted his cytoylobulin, which has
a pure anti-coagulative action (and is probably identical with
historic), from the lymph glands and other tissues — as above stated.
On the ground of many experiments, he maintains that the liquid
state of circulating blood must be regarded as a function- of the
living cells of the fixed tissues, with which the blood is in
continual exchange. These receive the nutrient matters from the
blood, and return to it the products of their metabolism, including
the globulins (the mother substance of fibrin) and cytoglobulin,
which obstructs the coagulative action of the ferment that con-
stantly diffuses in the blood owing to the disintegration of the
nuclei of the leucocytes. When the blood is extracted from the
vessels, cytoglobulin no longer pours in, while thrombin, owing to
the rapid alteration of the leucocytes, is abundantly present, and
coagulation takes place.

The latest experiments of Lilienfeld show the ease with which
nucleohistone, when introduced into the circulation, breaks up by a
process of which we are wholly ignorant, into its two components,
the coagulating leuconuclein, and the anti-coagulating historic,
which last is found in a free state in blood drawn off immediately
after the injection, and according to Wright is present in urine also.
Lilienfeld, however, makes no definite suggestion as to why, under
normal conditions of circulating blood, the anti-coagulative action
of the histone always outweighs the coagulative action both of the
' nucleic substances and of the ferment, even when the latter is
present in great quantities in the plasma, as occurs with the
innocuous transfusion of defibrinated blood or of simple serum.

In regard to this and other phenomena, which call for more
adequate explanation, we cannot at present feel satisfied with the
work that has been done, or the theories proposed, in reference to
blood coagulation.

The latest attempts to discover why the blood does not clot
within the vessels, admit the presence of an anti-thrombin, or
substance which neutralises the action of the small amount of
thrombin present in normal blood.

According to the observations of Nolf and others, the incoagul-

v THE BLOOD: PLASMA 141

ability of peptonised blood depends on the fact that under the
action of albumoses the leucocytes and endothelial vessels pro-
duce a substance which gives rise in the liver to a large secretion
of anti-thrombin, which is subsequently poured out into the
circulatory torrent.

VII. The blood plasma, of which we have enumerated the
principal constituents, presents as a whole a solution of organic and
mineral substances, which are partly in chemical combination,
partly a simple mixture in which the corpuscles are suspended.
After the physico-chemical theory of solutions had been established
by the work of Pfeffer, H. de Vries, Kaoult, Van't Hoff and
Arrhenius, the method was, later on, applied to physiology. The
determination of molecular concentration, osmotic pressure, elec-
trical conductivity and viscosity in the blood serum and other
tissue fluids of the body, is now of some importance, since it has
brought out certain striking facts which are the starting-point
of a new chapter on the 'physical properties of blood plasma.

Let us commence with certain theoretical considerations.

By the molecular concentration of a solution we mean the
number of dissolved molecules (irrespective of their chemical
nature) in relation to a given weight of solvent, which in the case
of the organic fluids is always represented by water.

Such a solution, introduced into the graduated tube of a
Dutrochet's endosinometer, in connection with a mercury mano-
meter, and separated from the solvent by a semi -permeable
membrane (i.e. one which permits the passage of the solvent, but
not of the substances dissolved), sets up a current through the
membrane by which the solution is more and more diluted, so that
the manometer column rises to a certain height, after which it
remains stationary. The pressure then recorded by the manometer
represents the osmotic pressure of the given solution.

Pfeffer showed experimentally that the osmotic pressure is
in direct ratio with the molecular concentration. Given this
relation, it follows that when the osmotic pressure of a certain
solution is known, its molecular concentration is known also, and
vice versa.

Perfect osmotic equilibrium between two solutions is obtained
each time that the solutions, separated by a semi-permeable
membrane, contain the same number of molecules in the same
volume of water, even if they are of different chemical constitu-
tion. Suppose, for instance, a solution of urea and one of sugar
to be separated by a membrane that is permeable to water but
not to the dissolved substances.. So long as one of the two-
solutions contains a larger number of molecules dissolved in
the same volume of water than the other, there will be a diffusion
of water from the more dilute to the more concentrated solution.
This diffusion ceases as soon as the number of molecules in the

142 PHYSIOLOGY CHAI>.

two solutions, in respect of the same volume of water, becomes
equal for the two fluids, although their chemical constitution
remains unlike, since the one contains only urea and the other^
sugar.

Solutions which are of equal molecular concentration, and
are therefore called equi-molecular, have also the same osmotic
pressure and are termed isotonic (from lu-os, equal, and TOI/OS,
tension). In fact, when separated by a semi-permeable membrane
they are found to be in osmotic equilibrium.

According to a law discovered by Eaoult (1S82), each molecule
of any substance dissolved in a given quantity of water lowers the
freezing-point of the water by a certain and always constant
degree, so that the lowering of the freezing-point depends on the
number of molecules dissolved, and not upon their weight or their
chemical constitution. The determination of the freezing-point
of different solutions is termed Cryoscopy, and the difference
between the freezing-point of the solution and that of the pure
solvent is indicated by the symbol A.

The cryoscopic method serves indirectly, by an easy technique,
to determine the molecular concentration and the osmotic pressure
•of any given solution.

The salts in general are an exception to Eaoult's Law, since
their solutions indicate a higher osmotic pressure than that which,
according to the law, should be exerted by the number of their
molecules. The molecules of these salts behave as if a portion of
them were split up. This led to Arrhenius' hypothesis of the
electrolytic dissociation, or ionisation, of dissolved saline molecules
— a phenomenon which is in strict relation with the electrical
conductivity of the solutions of salts, acids and bases, which are
called electrolytes, as distinguished from the solutions of non-
ionisable molecules which do not conduct electricity well, and are
known as anelectrolytes. This ionisation again is in relation with
the electrolysis which can be verified in these solutions on the
passage of a galvanic current. The dissociation of the molecules
of salts increases with dilution of their solutions.

Such in a few words is the modern physico-chemical theory of
solutions. We must now go on to examine some of the most
important results obtained by this method in regard to the osmotic
pressure and molecular concentration of blood serum.

These investigations were initiated in Holland by Hamburger,
and continued by others.

Hamburger's method is founded upon the resistance offered by
erythrocytes to diffusion of their haemoglobin when they are im-
mersed in a hypotonic solution, i.e. one in which the concentration
is less than isotonic. He sought to alter the molecular concentra-
tion of the circulating blood plasma, in order then to study its
•effects on the serum collected from a small quantity of shed blood.

v THE BLOOD: PLASMA 143

On introducing into the veins of a horse seven litres of a
hypertonic solution (solution of higher concentration than an
isotonic) of 5 per- cent sodic sulphate, he saw that the salt was
immediately eliminated by the excretory organs, the hyper tony of
the blood serum lasting only for a few moments after the injection,
although analysis of the same serum, when once more isotonic,
proved it still to contain a very abnormal quantity of sodium
sulphate.

Again, he found that the serum recovered its normal osmotic
pressure in a very short time after the intravascular injection of
a hypotonic solution of 0'5 per cent sodic sulphate.

He further found that the rise of osmotic pressure in the
serum, caused by the anhydraemia produced artificially by the
subcutaneous injection of pilocarpin and eserin (which cause
marked loss of water by exaggerated secretions of sweat and
saliva), lasts only a short time, as also the hydraemia occasioned
by copious bleeding.

Hamburger concluded from these facts that the vascular
system has the property of maintaining constant the osmotic
pressure of the plasma, notwithstanding the most varying changes
in the chemical composition of the blood.

He explained this fact on the hypothesis of a secretory
property of the vascular endotheliuni, which, when stimulated by
the increase or decrease of the osmotic pressure of the blood, reacts
by a rapid reinstatement of isotony. The secretory capacity of
the capillary endotheliuni was, as we shall see, experimentally
confirmed by Heidenhain.

Starting from these results, Winter made other experiments
with the cryoscopic method. He found that the freezing-point
of blood serum in the mammalia which he investigated was
practically constant. Freezing nearly always took place at
- 0'55° C., which point corresponds to that of a solution of 0'91 per
cent NaCl in distilled water. According to him, therefore, the
osmotic pressure of the blood, being independent of species and
individual, must in all probability depend, like temperature, on
the general conditions of the mammalian environment.

The 0'9 1 per cent NaCl is not hypertonic for erythrocytes as
some believe, but is much nearer their isotonic value than the
solution at 0'61 per cent, which rather represents the minimal
limit of concentration compatible with a rough anatomical in-
tegrity of the erythrocytes — apart, that is, from the changes in
shape which they undergo. In fact, it is shown by the observa-
tions of Hamburger, Malassez and others that the lowest
concentration of a solution of NaCl at which the erythrocytes
resist diffusion of their haemoglobin is 0'61 per cent. Even the
solution of NaCl at 0'75 per cent which for a long time was
considered physiological, is hypotonic. For man we must take

144

PHYSIOLOGY

CHAP.

the 0'90 per cent solution to be isotonic ; and although Winter
found the chlorides contained in serum to be, when expressed
in terms of NaCl, a little in excess of this figure — which re-
presents the extreme limit of corpuscular resistance (Q-62-0'72
per cent) — it must be remembered that the osmotic pressure of
the blood is due, not only to the chlorides, but, in a minor
degree, to other salts and organic molecules, so that the result
is considerably higher than it would be for the chlorides alone.
On the other hand Winter himself demonstrated, by means of
cryoscopy, that on dilution of the serum the molecular concentra-
tion is clearly higher than that previously expected from the
dilution, which he attributes to dissociation of the molecules of
NaCl. From these observations, that is, from the rich sodium
chloride content of blood serum, and from the ready ionisation of
its molecules, Winter was led to consider this salt as the com-
pensating factor in disorders of the osmotic conditions of the
blood and tissue fluids generally.

These results of Winter, in so far as they concern the relative
constancy of the freezing-point of blood serum in mammalia, are
unsatisfactory inasmuch as they disagree with the data previously
obtained by Hamburger and Gryns, and more recently by
Bugarszky and Tangl, and Bottazzi and Ducceschi. Here are
some of the data obtained by these authors : —

Hamburger.

Gryns.

Serum of horse

ox
?ig

A =0-596
0-585
0-620
0-568
0-647
0-621
0-605

Serum of horse

fowl

= 0-549
0-561
0-520
0-619
0-624
0-620
0-600

Bugarszky and Tangl.
Serum of horse .

cat
sheep

Bottazzi and Ducceschi.

: 0-527
0-531
0-532
0-570
0-605
0-585
0-601
0-633
0-613
0-588

Serum of frog
„ toad
„ tortoise .

5> »5 '

cock .
,, hare
dog

A =0-563
0-761
0-463
0-485
0-623
0-564
0-576

Fano and Bottazzi found in a series of cryoscopic observations
that the osmotic pressure of dog's serum presents only slight
variations from a mean value (higher than that found by Winter),
even when the animal has been subjected to the most various
organic injuries, such as splenectomy, asphyxia, inanition, anaemia

v THE BLOOD: PLASMA 145

from repeated bleeding, peptone injection, ligation of thoracic duct,
section of medulla oblongata.

These results exclude the hypothesis of a special regulatory
apparatus of the physical conditions of the blood, since they are
independent of the nutrition of the body, and the functional con-
ditions of the circulatory apparatus and nerve centres. It is
logical to assume that the practical constancy of the osmotic
pressure of the blood depends on the mutability of the physico-
chemical grouping of atoms, whether intra- or extra-cellular (in
the tissue fluids), through which adjustment to the disturbances
of osmotic equilibrium, and' compensation, are readily effected.
Besides the ionisation of the molecules of sodium chloride as
demonstrated by Winter, we may, according to Fano, hold that
the associations and dissociations of the salts with the proteins,
and the polymerisations and depolyrnerisations, come into play in
the rapid compensation of the abundant rise or fall of the osmotic
blood pressure.

Bottazzi's latest observations on the osmotic pressure of marine
animals prove that the value of the osmotic pressure of the blood
is more or less related to the general environmental conditions of
the organism. The blood, both of marine invertebrates and also
of the cartilaginous fishes, shows an osmotic pressure approximately
equal to that of sea-water (A = 2'2 - 2'3). In Teleosteans the
independence of the osmotic conditions of the tissue fluids from
the external environment of the organism begins to appear. Their
blood shows an osmotic pressure which is about half that of sea-
water, and intermediate between that of the cartilaginous fishes and
of the higher vertebrates, which, although they live in the sea,
make use of aerial respiration. The blood of these last exhibits an
osmotic pressure differing little from that of the higher terrestrial
vertebrates.

The special conditions which determine these differences have
still to be ascertained experimentally.

Bottazzi and Ducceschi in other interesting experiments
endeavoured to determine the relations between the resistance of
the erythrocytes to diffusion of their haemoglobin, the osmotic
pressure of serum, and the alkalinity of plasma in the different
classes of vertebrates. Their chief conclusion is that in the
blood of mammalia a certain ratio and mutual dependence
between all three factors can be observed, but that this
ratio or correspondence disappears in animals with nucleated
red corpuscles. It therefore seems probable that the presence
of a nucleus makes the erythrocytes to a certain degree in-
dependent of the physico-chemical factors of the fluid in which
they live, which (from a teleological standpoint) may tend to
maintain their integrity, particularly in the poikilothermic
animals, which are subject to perpetual changes of external

VOL. I L

146 PHYSIOLOGY CHAP.

environment. A mechanical explanation of the greater resist-
ance of nucleated erythrocytes to the diffusion of their haemo-
globin, even in very dilute solutions of sodium chloride, may",'
according to these authors, consist in the fact either that the
nucleus of the cell exerts a positive chemotactic influence on
the haemoglobin of the strorna, or that the haemoglobin makes
a more stable combination with the lecithin of the stroma.
In any case, it is clear from these results that the resistance of
the nucleated corpuscles is neither an expression nor a measure
of intracorpuscular osmotic pressure.

In a series of publications (1895-97) Manca (experimenting
always with the red blood-corpuscles of mammalia, i.e. with non-
nucleated erythrocytes) sought to determine the relations in these
between vitality and osmotic pressure, in order to distinguish the
physiological from the purely physical factors in the pheno-
mena of their resistance and osmotic exchanges with the plasma.
He set out from the conclusions of Hamburger, Limbeck, and
other physiologists and pathologists, who, in considering the varia-
tions of resistance offered by the erythrocytes to various physio-
logical and pathological conditions, interpret these phenomena as
dependent on changes in their vital conditions, and affirm that
only living erythrocytes obey the laws of osmosis and of isotonic
coefficients. The problem, attacked by Manca from various aspects,,
led to a consensus of results, which may be summarised in a few
words.

In experiments made with the venous blood of dogs, both
before and after prolonged muscular exertion, he found that the
resistance of the erythrocytes (determined by Hamburger's method)
underwent a slight but constant increase.

Erythrocytes treated in vitro with strong doses of cocaine
hydrochlorate, strychnine sulphate, atropine sulphate, morphine
hydrochlorate, showed less resistance than the normal, but
perfectly obeyed the same laws that govern the osmotic exchanges
of normal blood-corpuscles.

The resistance of the corpuscles left to themselves outside the
body, with no aseptic precautions, also diminishes gradually ; but
after 3-10 days (when, according to Hamburger, they must be
considered as dead) they react to solutions of NaCl and KC1 like
normal erythrocytes, and obey the same laws of osmosis. The
erythrocytes behave towards dilute solutions of the same salts in
such a way that it must be assumed that the molecules of NaCl
and KOI are equally dissociated or ionised, and that the erythrocytes
are either impermeable to them or permeable to the same small
extent.

The erythrocytes of the blood when treated in vitro with even
the strongest doses of chloroform, and those from the blood of
animals killed with chloroform, show a lower resistance than the

v THE BLOOD: PLASMA 147

normal, but perfectly obey the same laws that govern the osmotic
relations of normal blood-corpuscles.

In a series of experiments which Manca undertook with the
haematocrite method, using solutions of NaCl, KC1, LiCl, he
confirmed the previous results obtained with the colorimetric, or
Hamburger's method, even when the blood had been preserved for
two or three months, with or without aseptic measures, or even
after saturation with CO. From an average of seven experiments
with the haematocrite, undertaken to determine the degree of
concentration o"f NaCl isotonic with the serum and erythrocytes of
fresh defibrinated ox blood, he found that it corresponded with a
value of 0*82 per cent, a figure somewhat lower than that deter-
mined by the cryoscopic estimations of Winter, Fano, and
Bottazzi.

From the sum of Manca's results, it seems legitimate . to con-
clude that the so-called phenomena of resistance of the erythrocytes
(at any rate of those that are non-nucleated) and their osmotic
properties, are independent of their vitality, and that the red
corpuscles behave like simple, inorganic, artificial Traube's cells,
which consist of semi-permeable membranes.

The above are the most interesting results obtained by the
experimental analysis of the osmotic properties of the plasma and
blood -corpuscles. From these few indications it would appear
that we cannot as yet form a definite physiological opinion on this
important subject ; it did not, however, seem proper to omit the
matter completely, since it must obviously be of cardinal importance
in a not distant future.

Three methods in particular /ire to be recommended for the determina-
tion of the osmotic pressure of blood-serum and erythrocytes — that of Ham-
burger, founded on the resistance of the erythrocytes ; the cryoscopic, or
Raoult's method, founded on the lowering of the freezing-point ; and that of
Hedin arid Kcippe, founded 011 the determination of the volume of the
erythrocytes by means of the haematocrite.

Hamhuryer's method for determining the osmotic pressure of blood serum
is based on the examination of that solution of NaCl with which it is
isotonic. The erythrocytes of mammalia will only part with their haemo-
globin when the serum in which they are immersed is diluted with 50-60 per
cent distilled water. Thus, to find the value of the solution which gives the
exact osmotic pressure, it is only necessary to prepare some specimens of the
serum diluted to the required extent. Take six numbered test-tubes, 5 c.c. of
serum being added to each. To the first add 3*1 c.c. distilled water, to the
second 3 c.c., to the third 2-9 c.c., to the fourth 2-8 c.c., to the fifth 2'7 c.c., and
to the sixth 2'6 c.c. Then let three drops of defibrinated blood fall into each
test-tube, agitate the mixtures and centrifuge.

It is known experimentally that the NaCl solution isotonic with
mammalian blood, thus diluted, fluctuates between 0*55 and 0'65 per cent.
Pour about 8 c.c. of the following solutions of NaCl into six more test-tubes
similarly numbered— 0'62, 0'61, 0'60, 0'59, 0;58, and 0'57 per cent. Then, as
in the first series, let three drops of defibrinated blood fall into each tube,
.and shake.

After two hours the erythrocytes will have sunk to the bottom in all the;

VOL. I L a

148 PHYSIOLOGY CHAP.

test-tubes. In the first series the fluid will be red in some, colourless in
others.

When, e.y., they are red in the test-tubes to which 3*1, 3'0, and 2'9 c.c. of
water have been added, and colourless in the rest, the result works out as'/
follows : — The mixture of 5 c.c. serum + 2*9 c.c. water shows diffusion of blood

Slgment, while the mixture of 5 c.c. serum + 2*8 c.c. water remains colourless,
n examining the second set of test-tubes, the fluid is seen to be tinted in a
.saline solution of 0'58 per cent and in the weaker solutions, while the contents
of the tubes with the stronger solutions, 0'59, O60 per cent, etc., remain
tintinged.

The mixture of 5 c.c. .serum + — 9 water is therefore isotonic with a

solution of NaCl at ° )9-+-- -0'585 per cent.

Accordingly in calculating the NaCl solution isotonic with the normal
non-diluted serum, the following equation may be employed : —

5: 5 + 2-85 = 0-585 :z,

5 + 2'85xO'585
whence it follows that : x= — — — - — O92 per cent.

In this case the blood .serum is isotonic with a NaCl solution of 0'92 per
cent. . '

Raoult's Method.- — The determination of osmotic pressure by this method
is more easily carried out. The apparatus commonly adopted is that of
Beckmann (Fig. 43). It consists essentially of a glass vessel u, which is filled
with a free/ing mixture (crushed ice and salt), a test-tube B introduced to a
certain depth in the vessel (7, and a longer tube A fitted with a lateral tubey
which also dips into the tube B. The tube A is closed with a cork, through
the centre of which passes the special Beckmann thermometer D (or an
ordinary thermometer with a scale divided into hundredths of a degree) and
platinum wire F, which is bent into a loop at its lower end. This platinum
wire, which is intended to stir the fluid contained in the glass tube A, is
automatically set in motion by a little motor driven by water or electricity
or other power. In using the apparatus the vessel C is first filled with the
freezing mixture, then a few c.c. of serum are poured into the tube A till the
bulb of the thermometer is covered, when the stirrer F is set in motion. The
mercury column of the thermometer must be watched until, after sinking, it
rises again, and then remains for a few seconds at the temperature attainedr
which is the freezing-point of the liquid.

In practice, it is usual to assist the freezing and rise of the thermometer
by dropping a small crystal of ice into the liquid through the lateral tube E.

When the freezing-point, which Raoult indicates by A , has thus been
obtained, it is easy in the case of blood serum to calculate the solution of
' XaCl with which it is isotonic. If, &//., with ox serum, A = 0'55°, when the
1 per cent solution is found to freeze at - 0'588°, it can easily be calculated
that the NaCl solution isotonic with the serum under examination is equal
to 0'90 per cent.

Haematocrite Method. — This method (adopted by Hedin, Gartner,
Daland, Koppe, Eykman, Gryns, Maiica) is founded on the property possessed
by the red corpuscles of varying their volume with the variations of the
solutions with which they are in contact. On studying the action of
solutions of different concentration of the same substance (provided there is
no destructive action on the erythrocytes), these become smaller in more con-
centrated solutions, larger in more dilute solutions ; their volume is constant
only in a solution which is weaker than that which crenates the corpuscles,
and stronger than others which make them swell out On experimenting
with various substances these! observer's found for each a solution at which

V

THE BLOOD: PLASMA

149

the volume of the corpuscles remains unchanged. These solutions, taken as
isotonic, correspond exactly with those found by the methods of Hamburger
and Raoult.

The apparatus employed is practically the same as that described on p. 104,
Fig. 31, save that the capillary tube (haematocrite), 7 cm. long, is divided into
100 parts, finished at one end by a funnel-
shaped swelling.

To ascertain the solution of NaCl that is
isotonic with that of mammalian blood serum,
the first step is to aspirate into different
haematocrites a quantity as equal as possible,
and containing about 0*02 c.c. of blood corpuscles.
The haematocrites are placed in the horizontal
supports represented in the said figure, and,
centrifuged till the column of erythrocytes
becomes regular and constant, while the height
they reach is simultaneously noted. Next, to
the free portion in each haematocrite is added,
by means of a Pravaz' syringe or a measuring
pipette graduated in hundredths of c.c., a given
quantity (0'2 c.c.) of the various solutions of
serum, diluted in the same way as those em-
ployed in examination of the osmotic pressure
of the serum according to Hamburger's method.
The erythrocytes are mixed with the solution
by means of a fine needle, care being taken to
close the capillary end of the haematocrite with
the finger, and they are then again centrifuged
for an hour and a half, until the level of the
stratum of corpuscles remains constant. This is,
easily ascertained when, on reading the height of
the stratum of erythrocytes, at intervals of a few
minutes' centrifuging, they show the same figure.
On then examining with a lens the several
columns of fluid corpuscles, that solution is to
be taken as isotonic in which the column in
the haematocrite is level with the original.
If none of the columns are exactly in this
condition, the isotonic solution is intermediate
between the tube in which the corpuscles
are either just shrunk or just swollen, i.e.
the first is just hypertonic, the second is just
hypotonic.

Method of Electrical Conductivity. — The
cryoscopic method enables us to study the mole-
cular concentration of the blood and the serum,
that of electrical conductivity permits us to
study the electrolytes they contain. Accord-
ing to Arrhenius, electrical conductivity is due to the dissociated portion
of the electrolytes, to the positive and negative ions (kations and anions),
their number and their velocity in the fluid. It varies with everything
that causes the concentration and mobility of the ions to vary, such as the
chemical nature of the electrolytes, their molecular concentration, the
presence of anelectrolytes and colloids, the temperature.

The electrical conductivity (K) of a solution is the reciprocal of the
resistance (r), measured in ohms, which it offers to the passage of the
electrical current.

Resistance is measured by Kohlrausch's method with the apparatus shown

VOL. I L &

FIG. 43. — Beckmann's Cryoscope.

150

PHYSIOLOGY

CHAP.

in the schema of Fig. 44. Here 1 is the source of the induced current, r the
resistance of the liquid to be determined, R a resistance expressed in ohms,
T a telephone, x a contact that slides along a metal wire pq, which is kept
tense and parallel with a scale divided into 1000 parts and one metre in f*
length.

This arrangement constitutes the so-called Wheatstone Bridge, and no
electrical current passes through the telephone T, i.e. it remains silent, when
the contact x divides the wire pq into two parts, px and xq, such that the
resistances of px, xq, r and R are related thus : —

r : R --=px : xq.

FIG. 44.— Diagram of apparatus used for determining the electrical conductivity of fluids.

It is easy to find this point x by holding the telephone to the ear and sliding
the contact along the wire pq, the above ratio enabling us to calculate the

—, and noting that px + xq = 1000 : —

2 «

required resistance, as

The resistance capacity ((7) of the cell containing the fluid to be examined is
found by determining the resistance (2} which it offers with a given solution

of known conductivity (x), e.g. KC1 ^ and calculating C=x2. In all other

fluids to be examined in the same cell the specific electrical conductivity

C
is calculated on the basis of this value, « = -»-' The conductivity at 25°

of the serum of healthy human blood (Viola) calculated in ohms (ccxlO6)
oscillates between 1128 and 1232. That of the blood is much less, and at
the moment of clotting it presents a rapid diminution (Galeotti).

Besides osmosis and electrical conductivity, we must briefly
consider the physiological importance of another physical property,

v THE BLOOD: PLASMA 151

the viscosity of blood plasma, to which no one had called attention
previous to the interesting work of Albanese, On the Influence of
the Composition of Nutritive Fluids on the Activity of the Isolated
Frog's Heart (1893).

Let it be said in the first place that the viscosity of a homo-
geneous fluid, such as plasma or blood serum, is due to the internal
friction between its molecules and those of the solvent (water),
and of the bodies in solution or in pseudo-solution (colloids),
whether or no these are electrolytes, dissociated or non-dissociated ;
and that in heterogeneous fluids, such as the blood, entire or defi-
brinated, the viscosity is largely augmented by the presence of the
corpuscular elements.

It varies considerably with temperature, and is measured by
special instruments called viscometers. The measurement is based
on the time which a known volume of fluid takes to pass along a
capillary tube. When the pressure under which the fluid passes,
and the dimensions of the capillary tube, are known, it is possible
to obtain absolute values (/>) of viscosity ; but often it suffices
to obtain the relative value (17) by comparison with that of another
fluid, e.g. distilled water.

Hlirthle suggested another method by which it is possible to
determine the viscosity of circulating blood in the living animal ;
but better results are obtained experimentally in vitro and with
blood serum.

Bottazzi found the value 77 at 15° C. for dog's serum = 2-0233-
2-0486, and at 39° C. = 1-84-1-87 ; Mayer at 40° C. for mammalia
obtained values that oscillated between 1*41 and 1-95. In the dog
the viscosity of serum and defibrinated blood is as 1 : 5 (Bottazzi).

The viscosity of blood determined by Albanese with Ostwald's
viscometer (v. Grundriss der allgemeinen Chemie, Leipzig, 1890) is
approximately equal to that of a 2-3 per cent solution of gum
arabic. He believes in a certain constant ratio between isotonicity
and isoviscosity ; but this seems improbable, since the fluids within
the body are isotonic but not isoviscous.

The physiological importance of viscosity depends principally
on the great resistance which it entails on the blood passing
through the capillaries, and on the corresponding effort that must
be made by the heart. But it is probable that the high viscosity
of the blood and the presence of colloids influence some chemical
reactions in a way that does not obtain in pure water or in fluids
of less viscosity ; and this notwithstanding that the diffusion of
crystalloids in colloid solutions is effected with the same rapidity
as in water. From this it appears that a fluid, in order to be
completely physiological, that is to say, indifferent and innocuous
to the living tissues, must, besides being isotonic and isoconductive,
be also isoviscous, i.e. it must possess a degree of viscosity equal to
that of blood plasma.

152 PHYSIOLOGY CHAP.

VIII. In order to appreciate the importance of the functions
of the blood in the animal economy, it will be well to examine
briefly the most important consequences of haemorrhage and
transfusion of blood.

(a) Loss of blood, however produced, results in a weakening of
the body in correspondence with the amount of blood lost. A
haemorrhage of 30 grms. is dangerous or deadly in the new-born
infant, of 180-200 grms. in a child of one year old, of half the blood
(2000-2500 grms.) in the adult. Women appear to stand loss of
blood relatively better than men, because they have the power,
being subject to periodical haemorrhages (menstruation), of reform-
ing it more quickly. In consequence of the relative speed at
which blood forms again it is possible to obtain a greater volume
of blood by repeated bleeding than was originally present in the
animal, without causing its death.

Vierordt (1854) was one of the first to investigate the effect of
bleeding upon the number of red corpuscles, and he found that
they diminished continuously with successive bleeding, and ., that
death occurred when the relative quantity of blood corpuscles
fell below a certain limit, which differs for different individuals.
If the loss of blood is not pushed so far as to kill the animal there
will be an increased influx of lymph into the blood, by which more
water, with its contained salts and proteins, is taken up from the
tissues. The neo-formation of erythrocytes takes longer. A con-
dition of liydraemia then obtains, associated with oligocythaemia
and leucocytosis, due to the increased passage into the blood of lymph
which carries a greater number of leucocytes with it. All these
facts (and others which we shall discuss in speaking of haemato-
poiesis) have been substantially confirmed by recent observers
(Hayem, Bizzozero, Golgi).

(6) The effects of transfusion of blood are more important. We
must distinguish between direct transfusion, from vein to vein,
and indirect, viz. the injection of extracted and defibrinated blood,
between homogeneous transfusion of the blood of the same species
and heterogeneous transfusion of the blood of animals of other
species.

Direct homogeneous transfusion is readily tolerated. According
to the observations of Worm-Muller the normal quantity of serum
in an animal can be increased to 83 per cent, in consequence of
the great adaptability of the vascular system, without serious
symptoms. But if the increase of blood is carried too far, so that
its quantity is doubled, alarming symptoms occur, and when the
increase is raised to 145 per cent the animal dies from interstitial
haemorrhage, in consequence of vascular laceration.

If a certain quantity of blood is transfused, there will be a
rapid return to the normal, owing to increased elimination from
the kidneys. The proteins of the plasma are also reduced (if less

v THE BLOOD: PLASMA 153

rapidly) to the normal quantity, owing to their conversion into
nitrogenous waste products. A marked increase of urea in urine
is actually observed during the first (2-5) days after transfusion
(Worm-Miiller, Landois). The erythrocytes diminish far more
slowly, so that the blood for about a month is richer in corpuscles
(polycythaemia) and haemoglobin (Panum, Lesser, Worm-Muller).
The diminution of the corpuscles is due to the breaking-up of their
constituents, as manifested in a moderate increase in the* urea
excreted daily by the kidneys, and the bile pigments secreted by
the liver (Landois).

It is remarkable that a rapid consumption of transfused blood
is observed even during inanition. In a dog that has been sub-
jected to a prolonged fast, periodical transfusion does not hinder
progressive wasting of the body (Luciani).

Indirect, as well as direct, homogeneous transfusion is tolerated
(provided the amount be not excessive), although defibrinated
blood contains a considerable quantity of thrombin and of co-
agulative nuclein- containing substances. Panum succeeded in
replacing almost the whole of a dog's blood by other homogeneous,
defibrinated blood, without injury to the animal. In this case, no
plethora is produced ; the transfused blood is supported well by
the new individual, and shows no abnormal tendency to degenerate.
This indicates homogeneous transfusion as a rational measure to
avoid the danger of death in severe haemorrhage. Since, however,
in many cases death ensues not from deficiency of the nutritive
matters of the blood, but because the necessary mechanical conditions
of the circulation are wanting, it is simpler in practice to replace
transfusion of blood by intravenous injection of physiological saline
(0'9 per cent), as suggested by Kronecker. The salt water is of itself
capable of maintaining the circulation, giving time for new blood
to form, and thus averting the danger of death from haemorrhage.

Transfusion of heterogeneous blood is dangerous to the life of
the animal even when it is administered in moderate doses. It
provokes fever with haemoglobinuria (Ponfik), due to dissolution of
erythrocytes (Landois) ; capillary embolism, due to agglutination of
foreign blood -corpuscles (Albertoni) ; fibrinous clotting, extra-
vasation of blood, diarrhoea, cholaemia, and bile pigments in urine,
etc., all effects of the destruction of blood-corpuscles.

This toxic and specifically haemolytic action of the blood of an
animal in regard to the blood of another animal of a different
species is exhibited regularly, but in varying degrees, in the
different species. Thus the blood of certain fishes, e.g. of the eel
and lamprey, is excessively toxic to mammals (A. Mosso). In order
to kill a rabbit, it suffices to inject 0*5 grm. of eel's blood for each
kgrm. of the rabbit's, into the circulation or peritoneal cavity ; while
to produce the same effect with duck's blood, 7 grnis. are required ;
with dog's blood 40 grms. per kgrm. (Hericourt and Eichet).

154 PHYSIOLOGY CHAP.

The haemolytic or globulicidal toxic action of heterogeneous
blood depends rather upon the plasma than on the blood-corpuscles.
Approximately the same effect is produced by injection of '
heterogeneous serum (Landois).

(c) The capacity of the blood, or serum, to destroy the foreign
cellular elements that penetrate it, is intimately connected with
another, and, from the medical point of view, far more important
of its properties — viz. destruction of certain pathogenic bacteria ;
this constitutes a natural defence of the body against special
infectious diseases, and is even more important than the phagocytosis
attributed to the leucocytes.

Fodor (1887) and then Nuttall and Flugge (1888) were the first
to demonstrate the bactericidal properties of the blood of living
healthy animals. H. Buchner (1889) showed that these depend on
the very unstable proteins of the plasma, which derive from the
metabolic activity of the leucocytes or other cells, and which he
designated by the name of cdexins (from aAe^o-is, defence). He
found that the serum lost its bactericidal property on simple
dialysis with water, but not with physiological salt solution.

By this treatment the serum only loses its salts ; yet after the
restoration of its original molecular concentration it does not
recover its bactericidal activity. This is perhaps due to the fact
that the salts before dialysis are in some way bound up with the
proteins, which association, on account of its great instability,
cannot be reinstated when once disturbed by dialysis. The serum
also loses its bactericidal effect on warming to 55° C. for an hour
or to 52° C. for six hours, a fresh proof of the great lability of the
alexins.

The bactericidal action of one kind of blood is not common to
all other species, nor does it extend to all bacteria, only to certain
of them. Thus, e.g., the serum of human blood contains alexins
against the bacteria of typhoid and cholera, while it has less effect
upon Staphylococcus pyogenes, and none on streptococci and the
diphtheria bacilli and anthrax ; the serum of the rabbit and dog
will kill typhoid bacilli, while the serum of the calf and horse
'have not this power (Buchner) ; the serum of the rat kills anthrax
bacilli, while the serum of mouse, guinea-pig, rabbit and sheep has
no bactericidal effect upon them (Behring).

Yet more wonderful is the fact, which has been recognised for
some time, that recovery from certain infectious diseases is followed
by immunity to them. Behring and Kitasato (1890) discovered
the cause of this phenomenon to be that the said infections
develop as an after-effect (in the blood of those persons who
survive them) a previously non-existent property of rendering
the bacterial toxins innocuous. They further showed that if
the serum of an individual who has become immune to any given
infection be injected into other individuals in sufficient doses,

v THE BLOOD : PLASMA 155

it is capable of transmitting to those persons immunity to that
same disease, to which they would previously have been liable.
These facts cannot be understood without admitting that in such
cases the infective agent sets up a formation of special protective
substances or antitoxins in the body, which are then poured into
the blood, and which apparently consist in certain special modifica-
tions in the proteins of the plasma. We cannot, however, enter at
length upon this interesting subject without transgressing the
limits of a Text-book of Physiology.

BIBLIOGRAPHY

For Classical Bibliography of the Blood, see —

H. NASSE. Blut. Wagner's Handworterbuch d. Physiologic, pp. 75-220. Bruns-
wick, 1842.

For Modern Literature, besides recent books on Chemical Physiology (see p. 39 et
seq.), the two following monographs may profitably be consulted : —
A. SCHMIDT. Zur Blutlehre, Leipzig, 1892. Weitere Beitrage zur Blutlehre,

Wiesbaden, 1895.
R. v. LIMBECK. Klinische Pathologic des Blutes, Jena, 1896.

For Physico- Chemical Theory of Solutions, Molecular Weight, and Osmotic
Pressure, see : —
R. NASINI. Analogia tra la materia allo stato gassoso e quella allo stato di

soluzione diluita. Gazz. chimica It. xx. 1890.

T. GARELLI. Pesi molecolari. Enc. chim. Unione tip.-editr. torinese, 1894-95.
H. J. HAMBURGER. Die osmotische Spannkraft in den medicinischen Wissen-

schaften. Virchow's Arch. 140, 1895. Osmotischer Druck u. lonenlehre,

Wiesbaden, J. F. Bergmann, 1901.

For Bibliography of Concentration and Osmotic Pressure of Blood Plasma and
Resistance of Corpuscles, see —
H. KOPPE. tiber den Quellungsgrad der rothen Blutscheiben durch aquimolecu-

lare Salzlosungen, und iiber den osmotischen Druck des Blutplasmas. Du Bois-

Reymond's Arch., 1895.
J. WINTER. De la concentration moleculaire des liquides de 1'organisme. Arch.

de physiol. de Brown-Sequard, tome viii. 1896.
G. FANO e F. BOTTAZZI. Sur la pression osmotique du serum du sang, et de la

lymphe en differentes conditions de 1'organisme. Archives ital. de biologic, tome

xxvi., 1896.
G. MANGA. La Legge dei coefficient! isotonici nei globuli rossi del sangue conser-

vato fuori dell' organismo. Archivio di Bizzozero, vol. xx., 1896.
T. CARBONE. Contribute allo studio della coagulazione del sangue. Memorie

della R. Accademia di Scienze, Lettere ed Arti in Modena, Sezione Scienze,

serie in. vol. iii., 1900.
L. SABBATANI. Funzione biologica del calcio. Parte seconda : II Calcio-ione nella

coagulazione del sangue. Memorie della R. Ace. delle Sc. di Torino, serie

n. tomo Hi., 1902, pag. 213-257.

E. GARDELLA. Azione anticoagulante degli anioni in rapporto alia diluzione del

sangue. Archivio di fisiologia, vol. ii., 1905.
G. BUGLIA. Azione anticoagulante dei cationi in rapporto alia diluzione del

sangue. Archivio di fisiologia, vol. iii., 1906.
G. GALEOTTI. Ricerche sulla conduttivita elettrica dei tessuti animali. Lo

Sperimentale, anno lv., 1901.
G. VIOLA. Ricerche elettro-chimiche e crioscopiche sopra alcuni sieri umani nor-

mali e patologici. Rivista veneta di sc. med., anno xviii., 1901.

F. BOTTAZZI. Ricerche sull' attrito interno (viscosita) di alcuni liquidi organici e

di alcune soluzioni acquose di sostanze proteiche. Archivio ital. di biol., tome
xxix. (1898), Principii di Fisiologia, vol. i. Elementi di chimica fisica.
Milano, Societa editrice libraria, 1906.

156 PHYSIOLOGY CHAP, v

P. MORAWITZ. Ergebnisse d. Physiol., 4. Jahrg, 1905. (This synthetic review of
the Chemistry of Blood Coagulation comprises 490 references to papers.)

Recent English Literature : —

T. G. BRODIE. The Immediate Action of an Intravenous Injection of Blood

Serum. Journ. of Physiol. , 1900-1, xxvi. 48.
A. E. WRIGHT. On a Method of measuring the Bactericidal Power of the Blood

for Clinical and Experimental Uses. The Lancet, 1900, No. 4031, 1556.
A. E. WRIGHT. On the Measurement of the Bactericidal Power of Small Samples

of Blood under Aerobic and Anaerobic Conditions, etc. etc. Proc. Roy. Soc.

Ixxi. 54.
A. E. WRIGHT. The Action exerted on the Coagulability of the Blood by an

Admixture of Lymph. Journ. of Physiol., 1902, xxviii. 514.
J. BARCROFT. The Estimation of Urea in Blood. Journ. of Physiol., 1903,

xxix. 181.
E. P. BAUMANN. The Effect of Haemorrhage upon the Composition of the Normal

Blood, etc., etc. Journ. of Physiol., 1903, xxix. 18.
S. G. HEDIN. On the Presence of a Proteolytic Enzyme in the Normal Serum of

the Ox. Journ. of Physiol., 1904, xxx. 195.
R. BuRTON-Oi-iTZ. The Changes in the Viscosity of the Blood produced by

Alcohol. Journ. of Physiol., 1905, xxxii. 8.
R. BURNET-OPITZ. The Changes in the Viscosity of the Blood during Narcosis.

Journ. of Physiol., 1905, xxxii. 385.
G. N. STEWART. The Influence of the Stromata and Liquid of Laked Corpuscles

on the Production of Haemolysins and Agglutinins. Amer. Journ. of Physiol.,

1904, xi. 250 ; and 1905, xii. 363.
R. T. FRANK. A Note on the Electric Conductivity of Blood during Coagulation.

Amer. Journ. of Physiol., 1905, xiv. 866.
J. MELLANBY. The Physical Properties of Horse Serum. Journ. of Physiol.,

1906-7, xxxv. 473.
W. H. HOWELL. The Proteids of the Blood with Especial Reference to the

Existence of Non-Coagulable Proteids. Amer. Journ. of Physiol., 1906-7,

xvii. 280.
L. J. RETTGER. The Coagulation of Blood. Amer. Journ. of Physiol., 1909,

xxiv. 406.

J. MELLANBY. The Coagulation of Blood. Journ. of Physiol., 1909, xxxviii. 28.
J. MELLANBY. The Coagulation of Blood, Part II. The Actions of Snake

Venoms. Journ. of Physiol., 1909, xxxviii. 441.
H. E. ROAF. The Osmotic Pressure of Haemoglobin. Proc. Physiol. Soc.,

Journ. of Physiol. xxxviii. 1.

CHAPTEE VI

THE CIRCULATION OF THE BLOOD : ITS DISCOVERY

CONTENTS. — 1. Physiological necessity for the circulation of the blood. Schema
of cardie-vascular system. 2. Theory of Galen. 3. Discovery of the lesser cir-
culation ^question of the priority of Columbus, Servetus, and Vesalius. 4. Dis-
covery of the general circulation by Cesalpinus. 5. Completion of the work by
Harvey. 6. Discovery of the lymph circulation by Eustachius, Aselli, Pecquet,
Rudbeck, Bartholin. 7. Discovery of the capillary system, and direct observation
of the circulation by Malpighi. 8. Microscopic observations of the phenomena of
circulation : Spallanzani, Poiseuille, R. Wagner, etc. 9. Discovery of diapedesis
of blood-corpuscles and migration of leucocytes : Waller, Addison, Recklinghausen,
Cohnheim. Bibliography.

THE Blood, in order to fulfil its physiological task as centre
and agent of the metabolic exchanges of the whole body,
must be in perpetual motion within the vascular system which
contains it. If the blood remained stagnant, that portion of it
which lay within the capillaries of the pulmonary system might
indeed become saturated with oxygen, but would be unable to
conduct it to the parts where it is required, i.e. to the parenchyma
of the organs ; on the other hand, the portion contained in the
capillaries of the aortic system would become charged with carbonic
acid which could not be exhaled from the body. The blood of the
capillaries leading to the portal veins would become charged with
the nutritive materials taken up from without, but would be
unable to reach the organs that require feeding; while the
products of consumption, again, would accumulate in these organs,
since they could not reach the organs of excretion.

I. Owing to the intensity of metabolism necessary to the
maintenance of the principal vital functions, especially in the
higher animals, the arrest of the movements of the blood leads in
a few moments to death from asphyxia of all the tissues. The
vascular system is therefore provided with a pumping apparatus,
which serves to keep the blood in continuous rapid movement in
all parts of the body.

If we reduce the cardio-vascular system to a schema (Fig. 45),
we may distinguish anatomically a central organ, and the arterial,
venous, and capillary systems : physiologically, a right or venous,

157

158

PHYSIOLOGY

CHAP.

and a left or arterial heart, connected by a system of vessels
running centrifugally and another running cen tripe tally, which
are closed, and communicate by a capillary system. The system

of the lesser, or pulmonary, circula-
tion unites the ventricle of the
right with the auricle of the left
heart ; the system of the great, or
aortic, circulation connects the
ventricle of the left heart with the
auricle of the right. The auri-
culo- ventricular orifices and the
orifices of the two big arteries
which arise from the ventricles are
provided with valves ; the orifices
of the great veins, which open
into the auricles, have no valves,
although on the other hand valves
are plentiful along the course o£.
the veins.

The importance of the several
parts of the circulatory system is
very different. Only the capillary
portion serves the physiological
uses of the blood. The arteries
and veins are only paths to con-
duct the blood to the seat of its
activity, whence it is again returned
to the heart. The heart is the
motor, a perfect pumping machine
to circulate the blood, emptying
its contents into the arteries during
systole, filling itself again with
blood from the veins during dia-
stole.

The discovery of the Circula-

uiir; ir:iu ii'Miii, HI wiittni UI I ' • t M ( 'I l.U U1UUU , • /» .-• T"*l 1 J * 1 J 1

circulates. Blue indicates the vessels tlOn Ol the BlOOd IS Certainly the
connected witli the right heart, in which
circulates the venous blood. Yellow in-
dicates the lymphatic system, pc, Lesser,
or pulmonary circulation ; p, lung ; gc,
great or systemic circulation, formed by

Fie. 4/>. — Diagram of cardio- vascular system
lied indicates the vessels connected witl
the left heart, in which the arterial blood

im-iv^f anf oirnnf va^rvrrl^rl in

important event recorded in

the history of physiology. By it
, , J .. ,* J &J „ , J .

nearly the whole System of phySlO-

all the vessels of the aortic arterial system, -i i i JTll 1J

and the venous system of the venae cava ; logical and inedlCal knowledge, aS

SpCScirSm1\tOyvSS,.ce' handed down from antiquity, re-

ceived a violent wrench, and under-
went a fundamental reconstruction. With it begins the modern
science of physiology, founded on the ruins of the ancient doctrine.
It is indispensable that any one who aspires to physiological
culture should be acquainted at least in its main points with the
history of this great discovery (which has been misrepresented in

vi CIECULATION OF BLOOD: ITS DISCOVEKY 159

many text-books and monographs), and should know the names
of the men who have participated in its preparation or fulfilment.
In reviewing this interesting history we shall have an opportunity
of bringing forward those fundamental principles relating to the
Circulation, which must necessarily precede a more detailed treat-
ment of the subject.

II. The story of the discovery of the circulation begins with
Galen (125-201 A.D.), who in his vivisections perceived the error
of the Alexandrian school. Headed by Erasistratus (300 B.C.),
they taught that the left heart and arteries are empty of blood,
and connected with the small bronchi by means of the arteria
aspera (trachea), which serve to carry the vital spirits (pneuma) to*
the different parts of the body, to animate them ; hence the veins
alone would contain the blood destined to provide the whole body
with nutriment.

Galen showed that on puncturing any artery or the left heart
in a living being, the blood gushes forth, and, unlike that of the
veins, is pure, thin, and vaporous, due, that is, to a mixture of
blood with the air obtained through the lungs, " mix turn quid ex
ambobus."

According to Galen, the arterial centre is the left heart, which
drives the blood endowed with vital spirits (sang ids spiritosus)
through all the organs to invigorate them. The centre for the
veins, on the other hand, is the liver, from which the nutritive
blood (sanauis nutritious) is conducted by a kind of attractive and
selective force to every part of the body. The blood of the right
heart, supplied by the vena cava inferior, passes mainly through
the pores of the septum (which Galen accepts, although he declares
them invisible), becomes spirituous by admixture with the pneuma,
and is then distributed by the aorta throughout the body. A
lesser portion of the blood contained in the right ventricle passes,
however, through the vena arteriosa (pulmonary artery) and returns
by way of the arteria venosa (pulmonary vein) to the left ventricle.

Thus Galen had an idea, however rudimentary, of the pul-
monary circulation, and knew that the venous vessels anastomose
with the arterial, since he had observed that an animal could bleed
to death from one artery. One point, indeed, in his doctrine led
certain critics astray in their interpretation of the text. Galen
assumed that the blood of the arteria venosa (pulmonary vein)
flowed back to the lungs at each systole (by a sort of physiological
insufficiency of the mitral valve), in order to expel by expiration
the fuliginous vapours formed in the blood. He thus allotted to
the pulmonary vein a double and 'opposite task, i.e. that of first
carrying the arterial blood from the lungs to the heart, and then
returning a portion of the same with the vapours from the heart
to the lungs. Galen also assigned a double function to the portal
vein, and assumed that during digestion it carried the chyle to the

160 PHYSIOLOGY CHAP.

liver, and then when the intestine was empty carried the blood
from the liver back to the gut. These two errors of the porosity
of the septum, and the systolic reflux, have not a little weakened
the lustre of Galen's theory of the lesser circulation] it cannot,
however, be denied that he was the first to have any idea of it, as
was recognised (long before G. Oeradini once more pointed it out)
by competent interpreters, such as Harvey, Maurocordato, Douglas,
Haller and Senac, more particularly on the strength of a passage
in Cap. 1Q, Book VI. De usu partium.

Who, then, was the first to rectify and complete the Galenic
doctrine, by denying the permeability of the cardiac septum, and
determining that not merely part, but the whole of the blood
expelled from the right ventricle returns to the left by the
anastomosis of the pulmonary vessels ?

III. In the year 1553 the Spanish physician and theologian,
Servetus,1 published his book Christianismi restitutio, which led,
at the instigation of Calvin, to his death at the stake, by which
he perished in Geneva in the autumn of the same year. . Only two
copies of this book, which was a theological treatise, are extant,
the greater number having been burned, some at Vienna in
Daupliine, with the author's effigy, and the rest in Geneva, with the
author himself. It contains a passage in which Servetus describes
the lesser circulation, denying the communication between the
ventricles by the septum, and affirming that the blood passes from
the right ventricle into the lungs, where " flavus efficitur et a vena
arteriosa (pulmonary artery) in arteriani venosam (pulmonary vein)
transfunditur."

In 1559, some six years later, Realdus Columbus of Cremona,
for fifteen years prosector, and then successor to Vesalius in the
Chair of Anatomy at Padua, published his work De re anatomica
libri XV. at Venice, in which on page 177 there is a description of
the lesser circulation, and statement of the impermeability of the
septum. The author lays great stress upon this discovery, and
claims priority for it : " Nam sanguis per arteriosam venam ad
pulmonem fertur, ibique attenuatur ; deinde cum acre una per
arteriam venalern ad sinistrum cordis ventriculum defertur : quod
nemo hactenus aut animadvertit, aut script urn reliquit."

It is undeniable, if we examine the date of the two publications,
that priority of discovery belongs to Servetus ; and if it could be
proved (as was attempted by Tollin and Preyer in Germany, and
by Willis in England) that Columbus had read the Christianismi
restitutio of Servetus, the Cremonese anatomist could not be held
guiltless of plagiarism. Against this assumption, however, must

1 Mosheim's opinion that ''Servetus" or "Serveto" was the anagram of Reves
seems to be definitely confuted by Comenge, author of a memoir La Circulation
de la sanyre (1887), where it is proved that the full name of the Spanish doctor
and theologian Avas Michele Servet y Reves, and that lie was a native of Villanueva
di Sinena (Aragona), where his lather was a notary.

vi CIRCULATION OF BLOOD: ITS DISCOVEKY 161

be placed certain indisputable facts, which have been collected with
great acumen by G. Ceradini (187ti-77).

Ceradini points out that Valverde, a Spanish pupil of Columbus,
ascribes the impermeability of the septum to his master in an
anatomical treatise, which appeared in Rome in 1556. To this
there is a preface dated 1554, in which the author states that he
had already prepared the numerous plates that were to illustrate
his book, which must have taken him. at least twelve months.
This takes us back to 1553, the year in which Servetus published
the book that cost him his life. It is, further, only reasonable to
suppose that Columbus had developed his theory from his Chair
some years before publishing it in his treatise.

We know that the physiological passages of Christianismi
restitutio were first discovered at the end of the seventeenth
century. Ceradini shows that in 1571, G-. Giinther, who had
taught Servetus and Vesalius in Paris, described the lesser circula-
tion in the words of Columbus, praising him without allusion to
his pupil Servetus — a proof that he was unacquainted with the
C kristianismi restitutio. In all probability it was unknown in
Italy, as it is not upon the Index librorum prohibitorum, drawn
up by the Council of Trent, and published in Rome by Pius IV.
in 1564, which contains the two other heretical works of Servetus,
De Trinitatis erroribus.

Lastly, by comparing the two theories, Ceradini produced cogent
evidence that Columbus was no plagiarist 'from Servetus.

Columbus completely and unconditionally denied the per-
meability of the cardiac septum ; he affirmed that not merely the
vena arteriosa, but also the arteria venosa, were of a conspicuous
size ; he further contradicted (incorrectly) Galen's respiratory
function, that is the formation of smoky fumes in the blood,
and their expulsion by means of expiration. Servetus, on the
contrary, while denying the presence of openings in the septum,
admitted that " aliquid resudare possit " through the same, and
maintained Galen's doctrine by his assertion that the blood " in
ipsa arteria venosa inspirato aere niiscetur, et exspiratione a
fuligine expurgatur."

Without going so far as to support Ceradini's hypothesis that
Servetus learned the theory of the lesser circulation from Columbus,
and attempted to bring it into harmony with the older doctrines
of Galen, we cannot doubt that the Crenionese anatomist had
expounded his theory some time before the Spanish physician and
theologian published his.

Roth, too, whom Tigerstedt calls the most learned anatomist of
the sixteenth century, attributes the discovery of the pulmonary
circulation to Columbus, and he expressly adds that there was
nothing in favour of the opinion that Servetus had contributed to
it. It is interesting to follow Roth's arguments. He insists on

VOL. I M •

162 PHYSIOLOGY CHAP.

the fact that we have no direct means of estimating the anatomical
knowledge of Servetus.

He had indeed been dissector for Gltnther ; but the latter was ' !
a man of no originality, and his Institutiones of the year 1539
showed no advance on the 1538 edition of the anatomical works
of Vesalius, but was rather a retrogression.

Another argument is derived from analysis of the anatomical
passages of the works of Servetus. His theory of the oommunica-
tions between the nerves and vessels, as conjectured by Praxagoras,
was confuted by Galen and Vesalius. ' The impermeability of the
'ventricular cardiac septum belongs, as we have seen, to Columbus,
and the capacity of the pulmonary artery to an observation of
Vesalius. Added to this, Servetus never properly verified the new
anatomical observations, which he vaguely adopted ; and never
attempted criticism of arguments contrary to his own views ; nor
did he bring forward any valid anatomical demonstrations in
support of his position. From all this but cne conclusion is
possible. Servetus worked from books, and not from the subject ;
he was a compiler, not a practical anatomist.

He pieced together the doctrine of Galen, certain ideas of
Praxagoras, and the observations of Vesalius ; with the discovery
of the latter he perfected and completed Galen's rudimentary
views on the pulmonary circulation ; but by quoting from
Praxagoras, he made a step backwards, not merely behind
Vesalius, but behind Galen also. In short, Servetus, animated
by his desire to conciliate science with the Bible, promulgated a
speculative, not a real anatomy, an anatomia imaginabilis, not an
anatomia sensibilis.

Roth, therefore, confirms Ceradini's statements as to the
priority of Columbus over Servetus, in regard to the lesser
circulation.

It is interesting, again, to determine the part taken in this
great discovery by the Belgian Vesalius, the founder of modern
anatomy, to whom Flourens (1857) ascribed priority in the theory
of the impermeability of the septum, while the theologian Tollin
(1884) accused him of plagiarising from Servetus, an opinion also
maintained by Tigerstedt (1893).

In the first edition of his great work, De humani corporis
fabrica (1543), Vesalius says that he finds himself " driven to
wonder at the handiwork of the Almighty, by means of which the
blood sweats from the right into the left ventricle through
passages which escape human vision." In the second edition
of this work, published in 1555, he omits the expression of
admiration for the Creator, and declares himself unable to
understand how " per septi illius substantiam ex dextro ventriculo
in sinistram ne minimum quid sanguinis assunii possit." Accord-
ing to Tollin, Vesalius must have derived this more accurate mode

vi CIRCULATION OF BLOOD : ITS DISCOVERY 163

of thinking from the Christianismi restitutio, which had been
published two years previously, in 1553, by Servetus.

Foster, on the contrary, maintains that the passage quoted
from the first edition of Vesalius was an expression of irony on
the part of the author, who frequently made use of this means
when his personal opinions were in too forcible contrast with the
doctrine of Galen. In the second edition, when his own fame
was established, and the revival of anatomy had advanced with
giant strides, he suppressed the greater portion of these veiled
doubts, and openly expressed his own opinions. This hypothesis
of Foster, however, seems arbitrary and untenable, when we take
into account the temperament of Vesalius, and his critical, not to
say aggressive, attitude towards the doctrine of Galen, on account
of which Silvio gave him the nickname of " Vesanus."

On the other hand, Ceradini, by an elaborate comparison of
the contents and dates of some of the lesser publications of Vesalius
(which would take us too far afield if we entered upon it), showed
that he had learned the impermeability of the septum from his
prosector Columbus at Padua in 1542, and had defended this
doctrine at Pisa in 1543, without, however, explicitly deducing-
its physiological corollary, the theory of the lesser circulation,
which implied, as already recognised by Galen, an anastomosis
between the vena arteriosa and the arteria venosa. Vesalius
grudged any praise of Columbus, whom he never forgave for
having, as it seems, excited the students" of Padua to animosity
against him.

Without belittling the great services rendered by Vesalius in
the reform of anatomy, it may be held proved that he had no
direct share in the discovery of the circulation. Indirectly,
however, he contributed to the refutation of not a few of Galen's
fallacies, more particularly in regard to the theory of hepatic
haematopoiesis. The fact that the lumen of the vena cava is
larger in the proximity of the heart than it is nearer the liver,
in his eyes justified the return to Aristotle's theory of cardiac
haematopoiesis, and the admission that not only the arteries but
the veins also are dependent on the heart.

IV. When in the year 1543 Vesalius, in obedience to a wish
expressed by Cosimo I. dei Medici, who had appointed him
Professor at Pisa, addressed himself to giving a short course of
" amministrationes anatomicae " upon the fallacies of Galen, it is
probable that his hearers included Andreas Cesalpinus of Arezzo,
who was at that time barely nineteen years old, and to whom
belongs the great honour of having first recognised and demon-
strated the general circulation of the blood.

In 1571 the Aretine physician and philosopher published his
Peripateticarum questionum libri quinque, in which he assumes
a constant and physiological transit of the blood from the arteries

164 PHYSIOLOGY CHAR

to the veins, through the anastomosis, which he termed the " vasa
in capillamenta resoluta," to every part of the body ; this perpetual
forward movement of the blood from the vena cavae to the right'
heart, thence to the lungs, from the lungs to the left heart, and
from the left heart to the arteries was termed by him Circulatio.
He was the first to recognise the arterial structure of the
pulsating vessel, which arises in the right ventricle, and was
designated by Galen the vena arteriosa, and the venous structure
of the non-pulsating vessels, which had been known as the arteria
venosa. He also recognised that the blood in the arteries stands
at far higher pressure than that in the veins, and that in its
passage from the one to the other the capillary anastomoses offer
greater or less resistance according to the degree of their contraction
or dilatation.

Again, in his books De plantis, which appeared twelve years
after the Questiones peripateticae, and would alone suffice to
bring him undying fame as a forerunner of Linnaeus, Cesalpinus
affirmed that the blood " per venas duci ad cor, et per arterias in
universum corpus distribui."

In 1593 Cesalpinus published his Questionum medicarum
libri II., giving the experimental evidence for his theories. He
observed that when in a living animal a vein was exposed,
ligatured, and soon after cut below the ligature in the direction
of the capillaries, the blood which first flowed out was darker in
colour, and that which followed lighter. From this observation
he deduced with great acumen the physiological function of the
anastomoses that occur in almost every organ between the veins
and arteries, maintaining " venas cum arteriis adeo copulari
osculis, ut, vena secta, primum exeat sanguis venalis nigrior, deinde
succedat arterialis flavior, ut plerunique contingit."

He founded a second experimental proof of the circulation on
the fact that in any part of the body the ligatured vein swells
between the ligature and its capillary origin, and not between the
heart and the ligature, as would be the case according to Galen's
notion, " intercepto enim meatu, non ultra datur progressus ;
tumor igitur venarum citra vinculum debuisset fieri."

Notwithstanding this brilliant experimental evidence for the
doctrine of the circulation, as first brought forward by Cesalpinus,
certain writers, among them the celebrated Haller, maintained
that while the Aretine philosopher was undoubtedly acquainted
with the circulation, he recognised it solely for the sleeping, and not
for the waking state. This is founded on a quite erroneous inter-
pretation of a' passage in which Cesalpinus admits a certain
regurgitation of blood from the arteries towards the heart during
the waking state. Ceradini, with convincing logic, has shown the
absurdity of Haller's contention, to be explained perhaps by the
fact that as a member of the Royal Society of London he might

vi CIRCULATION OF BLOOD: ITS DISCOVEEY 165

have some interest in debasing the merit of the Aretine, in order
to exalt that of Harvey. It is unfortunate that Ch. Richet, in his
Dictionnaire de physiologic now in course of publication, should
repeat Haller's mistake in regard to Cesalpinus, since it has been
contradicted by Ceradini, whose historical
studies he has evidently not consulted.

A further and very convincing proof of
the circulation of the blood is the presence
of the valves, which occur abundantly along
the course of the veins, and are so contrived
that only the centripetal passage of the
blood is permitted, while the centrifugal is
impeded (Fig. 46).

This evidence was not, however, adduced
by Cesalpinus, for which he has been criti-
cised by Sprengel, a medical historian. As
a matter of fact, although Cannanus of
Ferrara described certain valves of the
azygos vein in 1547, and showed that
their concavity was directed towards the
heart, Fabricius of Acquapendente, a few
years later, found and demonstrated to his
students analogous valves in all the veins
that contribute to the vena cavae. This
discovery was first published in De venarum
ostiolis in 1603, some ten years after the
publication of Cesalpinus' Questiones peri-
pateticae.

On the other hand, it must be stated
that Fabricius, who first described the
valves of the entire venous system, did not
recognise their function, which is to check
the reflux of the blood in a centrifugal

direction, and promote it in the centri- FJG 46._Extenial iliac vein,
petal, by muscular force ; he assumed that
they were there to retard the current of
blood from the heart to the periphery of
the veins. Who, then, was the first to
establish the theory of the circulation upon
the function of the venous valves ?

Ceradini deserves much credit for bring-
ing forward a series of important docu-
ments, which lead us to the logical conclusion that the first to
discover the function of the valves of the veins was the famous
Petrus Paulus Sarpi, theologian and canonist of the Venetian
Republic, the friend and pupil of Fabricius. It is a fact
that some contemporary authors ascribed the discovery of the

slit down, and pinned
out to show the numerous
valves, in the shape of
swallows' nests, placed
singly or 'two to threa to-
gether, along its course.
(Calori.) «, Tunica interna,
stripped oft' and turned over
at b • c, valves ; d, tunica
externa ; e, orifices of branch
veins ; /, branching veins
cut through.

166 PHYSIOLOGY CHAP.

circulation to Sarpi. Frate Micanzio, Bartholin, Yesling, Gassendi,
Walaeus, all hail him as the discoverer. Yoss (1685) wrote that,
the circulation was discovered by Cesalpinus in Italy, Paulo "
8o/rpio Veneto in primis placuit. Yesling communicated to
Bartholin that after Sarpi's death he had seen one of his autograph
manuscripts in the hands of the Bros. Micanzio, in which the
circulation of the blood was described. The famous Dutch
physician Walaeus wrote in 1640 : " Paulus Servita Yenetus val-
vularum in venis fabricam observavit accuratius ... ex valvularum
coustitutione aliisque experimentis, sanguinis motum deduxit
egregioque scripto asseruit." Unfortunately, however, the manu-
scripts of Sarpi, which were preserved in the Servite Library at
Yenice, were destroyed by fire, with a great portion of the convent,
in September 1769, only one fragment from a letter cited by
Griselini in his book Del yenio di Fra Paolo Sarpi (Yenice,
1785) remaining, in which Sarpi alludes to matters by him
" observed and described in regard to the course of the blood in the
vessels of the animal body, and to the structure and function of
their valves"

Y. What, then, was the real merit of William Harvey, the
supposed discoverer of the circulation of the blood, after Columbus,
after Cesalpinus, after Sarpi ? Assuredly lie was not the first to
correct Galen's error as to the permeability of the septum, and to
affirm that the whole of the blood passes from the right heart to
the left through the pulmonary vessels ; this was the discovery of
Columbus. Nor was he the first to recognise the presence of
arterio- venous anastomoses, the passage of blood through the same,
and the centripetal direction of the blood-stream in all the- veins;
this was the great discovery of Cesalpinus. Nor, again, was he
the first to describe the valves of the veins, for they were known
to Cannanus, and were accurately described by his pupil Fabricius
of Acquapendente ; nor to discover their physiological office in the
circulation — this was the discovery of Paulus Sarpi. Nevertheless,
Harvey's merit was immense ; it consisted in a wider and stronger
development of the doctrine communicated by his predecessors, to
Which he gave a solid basis by means of countless vivisections and
ingenious experiments. He committed a grave injustice, however,
in claiming the whole merit of the discovery, inasmuch as he
ignored the work, and omitted to mention the names, of Cesalpinus
and Sarpi.

After the critical studies of Ceradini and also of Tollin (which
coincide in this matter) it would be absurd to pretend that Harvey
was not fully acquainted with the works of Cesalpinus, which were
published in Venice in 1593, some five years before Harvey settled
at Padua, where he remained for four years (1598-1602) as the
pupil of Fabricius of Acquapendente. His silence, when accused
of plagiarism by his contemporaries Micanzio, Yesling, Walaeus,

vi CIRCULATION OF BLOOD: ITS DISCOVERY 167

Riolan, Bartholin, and others indicates that he prudently avoided
a dispute in which he had much to lose and nothing to gain.
Willis, in order to explain Harvey's action, has recently advanced
the view that he was a freethinker, and anti-Trinitarian like
Servetus and Cesalpinus, whose works he certainly knew, and
with whose views he fully sympathised. As court physician to
Charles I., the severe persecutor of Anabaptists and anti-
Trinitarians, he could not own to these tendencies without grave
danger. Hence, being indisposed to martyrdom, he kept silence.
It is obvious, however, that while this might explain his attitude
towards Servetus, it could not apply in any way to Cesalpinus, who
was the Pope's chief physician, and is known to have performed the
necropsy of Filippo Neri, in describing which his orthodoxy is only
too apparent.

^N evertheless, Harvey's little book of 72 pages which came out
at Frankfurt in 1628, Exercitatio anatomica de motu cordis et
sanguinis in animalibus, is unmistakably the masterpiece of a
man of genius.

Even now, after more than two and a half centuries of scientific
discovery, this opuscidum aureum, as Haller termed it, arouses
the admiration of the reader by its lucid ideas, and the logical
arrangement of its observations, which were all founded on vivi-
section. With the exception of a few inaccuracies and errors every-
thing it contains is well observed and reasoned, and it may still serve
as the introduction to a deeper study of this interesting subject.

After exposing the cardiac region in the living animal, Harvey
noted that the heart is alternately in a state of motion and of rest.
During systole it rises and strikes the thoracic wall with its
apex ; it contracts in all its parts, more particularly in the lateral
portions ; it hardens, like the muscles of the upper arm when they
contract ; and in cold-blooded animals it becomes pale when the
blood is emptied out of its cavity. The diastole or pulse of the
arteries coincides with the heart's systole. When the heart stops,
the arteries cease to pulsate. On opening an artery the blood
gushes out at every systole. Hence at the moment of systole the
blood is forced into the arteries, and cannot flow back, because
the valves hinder the reflux.

The auricles contract and relax together like the ventricles, but
before them. The movement appears to start from the auricles
and then reaches the ventricles. When the heart dies the left
ventricle is the first to stand still, then follows the left auricle,
then the right ventricle, the ultimum moriens being, as noted by
Galen, the right auricle. If the apex of the heart be cut when the
right auricle alone is contracting, the blood is seen to gush out at
every beat. The blood, therefore, reaches the ventricles in conse-
quence of the contraction of the auricles, and not by aspiration
due to distension of the ventricles.

168 PHYSIOLOGY CHAP.

The office of the heart in its movements is to drive the blood
from the veins to the arteries, and distribute it throughout the
body. Since the ventricular septum is impermeable, the whole of
the blood must, as recognised by Columbus, traverse the lungs by
the arterial vein and the venous artery, in order to pass from the
right to the left ventricle. None of this is fundamentally new ;
it is only the correction of certain fallacies of Galen in regard to
the movements of the heart.

The concept of the general circulation is expressed clearly by
Harvey in the following words : " Patet sanguinem in quodcumque
membruni per arterias ingredi, et per venas remeare ; et arterias
vasa esse deferentia sanguinem a corde, et venas vasa et vias esse
regrediendi sanguinis ad cor ipsum ; et in membris et extremitatibus
sanguinem (vel per anastomosin immediate, vel mediate per carnis
porositates, vel utroquoque modo) transire ab arteriis in venas;
sicut ante in corde et thorace a venis in arterias ; unde in circuiturn
nioveri, illinc hue et hinc illuc, e centre in extrema scilicet, et ab
extremis rursus ad centrum, manifestum fit."

To establish his theories he gives experimental evidence of the
three following propositions : —

1. The blood expelled by the contractions of the heart passes
incessantly from the vena cava to the arteries in such quantity
" ut ab assumptis suppeditari non possit, et adeo ut tota inassa
brevi tempore illinc pertranseat."

2. The blood driven forward by the arterial pulses penetrates
continuously to every member or part of the body, " majori copia
multo, quam nutrition! necessarium sit, vel tota massa suppeditari
possit."

3. " Ab uno quoque membro, ipsas venas hunc sanguinem
perpetuo retroducere ad cordis locum."

The experimental proof of the first proposition is the most
original part of Harvey's work. Starting from the capacity of the
right ventricle in man (which contains a little over 3 oz. of blood)
he pointed out that a considerable quantity of blood must be
driven into the arteries at each systole, owing to the width of the
orifices and the force of contraction. Whatever this quantity, it
must be in relation with the difference in the capacity of the con-
tracted and the dilated ventricle. If the heart of man or other
animals expels only one dram of blood in one contraction, and if it
contracts a thousand times in half an hour, then in this short time
it must drive ten pounds and five ounces of blood into the arteries,
a quantity far too large to be derived from the nutritive elements
taken into the system, unless the blood returns by the same path.
On opening, not the aorta, but any small artery, the whole of the
blood in the body escapes in less than half an hour, as was noted
by Galen.

The evidence for the second statement is merely an extension

vi CIRCULATION OF BLOOD : ITS DISCOVERY 169

of the experiments and ideas of Cesalpinus. When the arm is
tightly ligatured, as for an amputation, the arterial pulse disappears
at the periphery, while centrally the arteries pulsate more strongly
and swell up. The hand and arm become cold after a time.
When the arm is ligatured loosely, as for blood-letting, the arm
swells below the ligature, and the veins become prominent and
varicose. Above the ligature, on the other hand, they are invisible.
Tight ligatures impede the now of blood through the arteries, a
loose one only blocks it in the veins. The blood, therefore, passes
from the arteries into the veins. In this Harvey, in slightly

FIG. 47. — Reproduction of two first figures in Harvey's work (edition, 1(539, ex ojffidna Joannis
Maire, Ludguni Borfavorum). Pig. 1 is an exact imitation of the figure in the DC cenarum ostiolis
of Fabricius. The arm is bandaged at AA, as for bleeding. The turgid veins are seen, with
swellings at B, C, D, E, F, caused by the valves. These occur not merely at the points of
bifurcation (E, F), but elsewhere (C, D). Fig. 2 represents the same arm, from which the
blood has been expelled by pressure with the finger from 0 to 77. The vein between 77 and 0
is now obliterated, because at the point 0 there is a valve, which prevents the blood from
flowing back to 77, and at H the compression of the finger impedes the passage of the blood from
the peripheral veins.

different words, repeats the conclusions of Cesalpinus : " Apparet
qua de causa in phlebotomia . . . supra sectionem ligamus, non
infra." The conclusion that the blood flows to the several organs
in much larger quantity " quam nutritioni sufficiens sit," is again
taken from Cesalpinus, who described as " alimentum nutritivum "
what is brought by the blood to nourish the organs, as " alimentum
auctivum" what returns to the heart, after passing from the
arteries to the veins by the capillaries.

The demonstration of the third point is founded entirely, on
the physiological function of the valves of the veins. Harvey
treats this point with great subtlety, since his chief concern is to

170 PHYSIOLOGY CHAP.

convince the unbelieving, and he gives four figures of ligatured
arms (one of which is an exact reproduction of the " Figura I.,
Tabulae II. brachii vivi ad sanguinis missionein ligati " from the
treatise of .his master Fabricius, De venarum ostiolis) which
demonstrate the varicose and congested veins at points correspond-
ing with the position of the valves (Fig. 47").. The valves are not
intended to hinder the accumulation of blood in the lower parts of
the body, for they are found also in the jugular veins, which run
down from above, in the renal and mesenteric veins, etc. These
impede the flow of blood from the greater to the lesser veins, to
prevent their becoming lacerated and varicose ; they show that
the blood in the veins flows, not from the centre to the extremities,
but from the extremities to the centre. Injections from the greater
to the lesser veins are often arrested by the resistance of the
valves, while no difficulty arises in injecting from the small to the
great veins.

If the blood in a vein is compressed with the linger in the
ligatured arm, it will be seen that the blood which has passed
beyond the swelling (formed by a valve) cannot regurgitate, and
the portion of the vein between the swelling and the linger seems
to be obliterated. The function of the venous valves is therefore
the same as that of the semilimar valves of the aorta and the
vena arteriosa (pulmonary artery), which close the ostiurn and
hinder the blood from flowing backward.

VI. It might be thought that the Theory of the Circulation of
the Blood as demonstrated by Cesalpinus, and completed by
Harvey, would have won its recognition in science, and have been
universally accepted and adopted.

Opponents, however, were not wanting, among the most
important and stiff-necked being Jean Eiolan, the famous Parisian
anatomist, and Kaspar Hoffmann, a celebrated German scientist of
the day, who, like Harvey, had been a disciple of Fabricius of
Acquapendente. They recognised that the new doctrine under-
mined the foundations of the medical science of their day, and all
means seemed to them lawful to avert what they held to be a
serious danger. Needless to say, this opposition (although it
showed up certain defects and fallacies in the work of Harvey)
only succeeded in spreading the new doctrine more widely, and
making it better appreciated. Ceradini's observation is very apt,
to the effect that " Harvey owed his fame to the Parisian anatomist
who, after the death of Fabricius, was reckoned the first authority
in Europe; and the error of the English partisans lies in the
parallel they established between the impression produced on
the scientific world of his day by his writings and those of
Cesalpinus. Had Cesalpinus in his lifetime encountered a Kiolan,
to accuse him of plagiarism, of absurdity, and of heresy ; had he
not for more than thirty years developed peacefully from his

vi CIRCULATION OF BLOOD: ITS DISCOVERY 171

professorial chair, first at Pisa and then in Home, his ideas on the
circulation, without laying stress on their possible consequences
and eventual applications, no one would have contested with him
the glory of the discovery." Harvey, for the rest, was so far from
suspecting the wide-reaching consequences of the theory of the
circulation, as he had learned it from the Aretine, that it only
occurred to him to put it into print after publicly discoursing of
it to his pupils for nine years, when he was compelled to this
Course by the fact that the doctrine had brought him on the one
hand friends and disciples, on the other enemies and opponents,
and that these last were making a mighty disturbance. And even
after its publication in 1649, the physiological importance of the
theory appeared to him so problematical, that in his reply to
Eiolan, who refuted it, because he saw in it " neque efficientem,
neque finalem causam," he could find nothing better to say than
" Prius in confesso esse debet quod sit antequam propter quid
inquirendum. . . . Quod sunt in physiologia, pathologia et
therapeia recepta, quorum causas non novimus, esse tamen nullus
dubitat ? "

Obviously, so long as the Aristotelian doctrine, as resuscitated
by Cesalpinus and Harvey, flourished, — to the effect that the
function of the lungs consists in reviving the blood, and that these
organs, in which the blood becomes once more spirituous and
subtle, are nourished by the crude blood flowing back from all the
other organs ; so long, especially, as the laboratory for the blood,
and the paths by which the products of food digestion reached the
circulation, remained unrecognised — for so long did the theory of
the circulation of the blood fall short of its true significance, and
appear to be merely a physiological curiosity.

Certain passages of Galen indicate that Herophilus and
Erasistratus, the heads of the Alexandrian School (3000 B.C.),
observed the chyle vessels in the mesentery of sheep. At the
end of the seventeenth century Portal, and more than a century
previously Fracassato, pointed out that the celebrated Roman
anatomist Eustachius (Opuscula anatomica, Venetiis, 1564) in
studying the course of the azygos vein in the horse had recognised
the thoracic duct, and even detected some of its valves. It is
certain, however, that save for a vague tradition, all trace of these
fortuitous and isolated observations had been lost when the
Cremonese Gaspare Aselli, Professor of Anatomy at Pavia, found
the chyle vessels, which he termed lacteals, in the dog's mesentery,
in 1622. So fortunate did he esteem himself, as he relates, in
having found what he was seeking, that "conversus ad eos qui
aderant ; evprjKa inquam cum Archirnede." But he had no inkling
of the true function and physiological importance of these vessels.

In the year 1648 Pecquet, a young physician of Dieppe, who
was studying at Montpellier, noted that the lacteals carried their

172 PHYSIOLOGY CHAP.

contents not to the liver, as had been supposed by Aselli, but to
a large vessel which he rediscovered after Eustachius, the thoracic
duct, which empties itself into the subclavian vein. Two years
later, the lymphatics of the liver were discovered by a Swede,
Eudbeck, who recognised that they, too, emptied their contents
into the thoracic duct. Finally, in 1652, the celebrated Danish
anatomist, T. Bartholin, discovered the same vessels in every part
of the body, and found that they all flowed, with the chyliferae,
into the thoracic duct. In order to extend the theory of the
circulation, which he attributed to Harvey, he brought out a new
edition of his Anatomy, ad sanguinis circulationem reformata,
in the legitimate conviction that he had found a new and
invaluable argument, even though an indirect one, in its
favour.

" Eiolan," adds Ceradini, " Eiolan himself, the adherent of
every old tenet and opponent of all that was new, on this occasion
held back the darts of his criticism, that he might not blunt them
against the weight of i'acts. Harvey alone rejected chyle as well
as lymph vessels, together with the function of the thoracic duct,
and died, without retracting his views, in 1658, six years after
Bartholin."

VII. One last decisive step was wanting to complete the new-
doctrine and bring it into prominence — the discovery of the
capillary vessels and direct observation of the circulation through
these from the arteries to the veins. " Supererat," as said Haller,
" ut ipsis oculis circuitus sanguinis subjiceretur."

Galen, as already stated, was the first to postulate a direct
connection of the arterial and venous blood in the organs, figuring
it as a direct anastomosis or conjunction of the two sets of vessels.
This did not correspond with the notion of Cesalpinus, who
certainly admitted that the communications were made by " per
vasa non desinentia, ulterius trasmeantia" or "per vasa in
capillamenta resoluta " (which Harvey translated into " per carnis
porositates "), thus divining the existence of that new order of
vessels, joining the arteries with the veins, which were subsequently
termed capillaries.

Marcello Malpighi, in 1661, was the first to see the movement
of the blood in the capillaries of the frog's lung under the micro-
scope. He exclaims, " Talia mihi videre contingit, ut non im-
merito illud Homeri usurpare possim ad rem praesentem melius :
magnum certum opus oculis video " (Fig. 48).

After Malpighi, Leuwenhoek, Cooper and Haller tried in vain
to repeat this observation on warm-blooded animals. The first
who succeeded was Lazzaro Spallanzani, who bethought himself of
using the hen's egg during the development of the embryo. The
enthusiastic words in which the great physiologist records his
discovery are pleasant reading : " Long have I been burning with

vi CIKCULATION OF BLOOD : ITS DISCOVEEY 173

curiosity to discover the circulation in warm-blooded animals, and
to grasp it as completely as in the case of the cold-blooded ;
hence these vessels " (umbilicals of the chick) " attracted my
observation more than any others, and invited my consideration,
because they belonged to the said animals. Since the room in
which I found myself was insufficiently lighted, and I was
determined at all costs to satisfy my curiosity, I decided to
examine the egg in the open, under direct sunlight. After fixing
it in the apparatus of Lyonet " (a small microscope used by
Spallanzani) " I turned the lens upon it, and, notwithstanding the
strong light that surrounded me, was enabled by focussing my
eyes, to see plainly how the blood iiowed in the entire circuit of
the arterial and venous umbilical vessels. Thrilled with this

FIG. 4s. — Holmgren's Apparatus (improvement on Malpighi's method) for observing the pulmonary
circulation in a curarised frog. V, screw to regulate position of glass plate, P, which is in-
tended to keep the surface of the frog's lung flat ; (.', cannula'jclosed at the end by an elastic
membrane, which, when introduced into the glottis and blown up, closes the opening, so that
the lung cannot distend. - u j,^ .

unexpected joy, I felt that I, too, might exclaim, ' I have found it !
I have found it ! ' I made this discovery in May 1771, and employed
myself in the summer vacation of that year with its development."

These observations of Malpighi and of Spallanzani, a century
apart, constitute one of the most striking incidents in the history
of medicine ; no one has ever contested with Italy the honour of
having initiated the direct observation of the circulation. Modern
scientists, with more perfect microscopes and a more elaborate
technique, have only succeeded in completing the description of
the phenomena of the circulation, as visible under the microscope.
These must now be briefly described, since they contain some
interesting data that should precede the study of haemodynamics.

VIII. In direct observation of the transparent parts of the
living animal under the microscope the blood is seen to circulate
in a closed system of capillary canals, which unite the arteries with
the veins by a network, and form a continuous circuit. That was
the true discovery of Malpighi.

174 PHYSIOLOGY CHAP.

In all the vessels a sharp delimitation can be seen under the
microscope, in the form of two parallel dark lines, which represent
the walls of the vessels. In the most transparent and superficial
parts, the structure of the vessel walls can also be made out to a
certain extent below the tissues that cover them.

The movement of the blood within the vessels, which is visible
by means of the transported corpuscles, is continuous, and is always
in the same direction, save in a few branches of the capillary net-
work, in which a temporary block, due to the accumulation of
blood -corpuscles or a transitory reversal of the current, can
occasionally be detected (Spallanzani).

In certain vessels the current is centrifugal, that is, it sets
from the greater trunks to the lesser ramifications. In others it is
centripetal, i.e. from the lesser ramifications to the greater trunks.
The former are evidently arterial vessels, the latter venous.

In the arteries the current is continuous, with rhythmical
accelerations ; in the veins it is continuous and uniform ; in the
capillary network it is irregular, subject to impediments, arrests,
deviations, or accelerations, according as the blood corpuscles are
dispersed or accumulated.

In the medium vessels, arterial as well as venous, a more rapid
axial, and a far slower peripheral current can be distinguished
(Poiseuille, 1834). The erythrocytes move compactly along the
axial stream, and between them and the vessel walls on both sides
a thin streak of clear plasma is plainly visible, in which the leuco-
cytes move at irregular distances from each other, ten to twelve
times slower than the erythrocytes. The diameter of this clear
layer, which is occupied by plasma and leucocytes, and its relation
to the diameter of the axial current, varies considerably in the
different vessels, even in those of equal cross-section.

K. Wagner described as characteristic of the blood-stream in
the lungs and gills, a complete absence or excessive tenuity of the
parietal stratum, and lack of separation between leucocytes and
the erythrocytes — the time required for such separation being cut
short, owing to the greater current velocity and less extensive path
of the lesser circulation.

Poiseuille designated the parietal layer as the stratum
adhesivum, and considered it to be immobile or capable only of very
slow motion. From the theoretical standpoint, however, it is only
the thinnest stratum of plasma immediately bathing the internal
walls of the vessels that can be termed immobile. There can be
no doubt that the separation of the slower peripheral from the more
rapid axial current is a phenomenon of adhesion and of internal
friction caused by the viscosity of the blood plasma. Hydrodynamic
observations on the nature of the movement of fluids in tubes have
determined that the velocity of motion is increased for the axial
portion of the current, and decreases gradually from the central to

vi CIKCULATION OF BLOOD: ITS DISCOVEKY 175

the peripheral fluid cylinders, being lowest or nil in those imme-
diately adhering to the walls of the tube.

This decrease of velocity of movement from axis to periphery
'of the fluid cylinder, as represented by the blood, fully explains the
rotation of the leucocytes in the plasmatic layer round an axis
perpendicular to the direction of the current. The necessity of
this rotation is obvious, when we consider that the leucocytes
nearest the axis of the vessels are under the influence of a more
rapid current than those nearest the walls.

The explanation of the fact that the leucocytes are nearly
always in contact with the walls of the vessel while the erythro-
cytes move along the axial stream, is not (as many think) that
some viscosity of their surface makes them adhere to the walls, but
lies in the difference between their specific gravity and that of the
erythrocytes. It can be demonstrated in the microscope that
granules of graphite, carmine, and colophonium suspended in
water, and made to circulate in capillary glass tubes, behave like
the red and white corpuscles in respect to parietal and axial
currents. The granules of graphite, being specifically heavier, swim
in the axial current ; the particles of carmine, which are specifically
lighter, follow the marginal stream. On the other hand, these last
occupy the axial current, when they are made to circulate with
grains of colophonium, since the specific gravity of the latter is
lower than that of carmine. It has also been determined experi-
mentally that the leucocytes leave the parietal current and follow
the axial, when they are made to circulate, not with erythrocytes,
but with drops of milk, which are specifically lighter (Funke).

IX. The phenomenon of diapedesis of blood-corpuscles, alluded
to in Chap. IV., which may be observed in the microscope, deserves
special mention on account of its great importance.

Cohnheim, in 1867, was the first who directed the attention of
biologists to the fact of the active emigration of leucocytes from
the blood-stream through the uninjured vessel walls. He founded
on this fact a new theory of inflammation and suppuration which
is a complete antithesis to that of his celebrated teacher Virchow.
The same facts, however, had been observed and described in 1846
by Waller, who was the first to recognise the identity of the
leucocytes and pus corpuscles, but regarded the migration of the
blood-corpuscles as a phenomenon of filtration.

In 1849 W. Addison formally expressed the concept of an
active emigration of the leucocytes, and distinguished various
stages in the course of the phenomenon.

In 1864, v. Eecklinghausen discovered and described the
movements of the leucocytes through the spaces of the connective
tissue and the lymphatic canaliculi of such tissues as the cornea,
which have no blood-vessels, distinguishing between the fixed and
the movable or migratory cells. He did not investigate the origin

176 PHYSIOLOGY CHAP.

of the migratory cells, but his work was obviously (as stated by
P. Heger) " the true introduction to that associated three years
later with the name of Cohnheim."

We must now briefly describe the facts that can be observed
without difficulty either in the mesentery or the tongue of the
frog, after it has been paralysed with curare, or its spinal cord
destroyed, when a certain amount of neuro-paralytic dilatation of
the small arteries is produced.

When the peritoneum is exposed to air, the circulation in the
peritoneal vessels exhibits a marked retardation after about an
hour, so that (with a magnification of 200 to 300 diameters) the
corpuscles can not only be seen distinctly circulating in the
capillaries and veins, but also in quicker motion within the small
arteries.

This delay has no sooner begun than a partial block and

FIG. 49. — (Jolniheim's apparatus for studying the course of the circulatory ; phenomena
in inflammation of frog's peritoneum.

accumulation of corpuscles will be observed in the capillaries,
which gradually disappears in some places to reappear in others.

In the small veins the most conspicuous feature is the im-
mobilisation of the leucocytes on the internal walls of the vessels.

As they leave the capillary network, they advance with a rotary
motion along the wall of the vein, and become fixed in contact with
those that are already immobilised. Little by little they cover the
' entire internal surface of the small veins, forming a hollow cylinder
of motionless leucocytes surrounding the cylinder of moving
erythrocytes.

On continuing to observe the leucocytes clinging to the walls
of the small veins and capillaries, it is possible in about two hours
from the beginning of the experiment to catch the corpuscles in
flagrante, in the very act of traversing the vessel walls to penetrate
into the meshes of the connective tissue or into a lymph sheath, or
the surface of the serosa. Here and there on the outside of the vessel
an irregular lump of protoplasm is seen, which forms a sort of hernia,
and is continuous with the intravascular portion of the protoplasm
of the corpuscles. The external portion of the corpuscle becomes

vi CIRCULATION OF BLOOD: ITS DISCOVERY 177

gradually larger, while the in tra vascular portion — still keeping
its round shape — continuously diminishes in volume, till at last it
appears only as a mere shining point, and eventually disappears
altogether. The extravasated leucocyte is then seen completely
free from the vessel ; it resumes its circular shape, and remains
motionless.

The direct observation of diapedesis can be facilitated by staining
the leucocytes of the blood with methylene blue or other colouring
matters introduced into the dorsal lymph-sac of the frog — the
method of Cohnheim.

Recent researches have left no doubfc that the diapedesis of
leucocytes is an active phenomenon, intimately connected with
their amoeboid mobility. The extravasation of red corpuscles (the
true haemorrhagia pw diapedesin, as divined by the ancients) is, on
the contrary, a passive process, depending either on rise of intra-
vascular pressure or on nutritional disturbances and lowered
resistance of the capillary walls.

In the frog's peritoneum the extravasation of the erythrocytes
(from the capillaries rather than from the veins) is first noticed
after several hours, and becomes conspicuous only twenty-four
hours after the beginning of the experiment, in the capillary
network where the circulation is at a standstill and the block of
corpuscles is greatest.

This observation led Cohnheim to the opinion that the leucocytes
penetrate through tiny pre-formed stoniata in the vessel wall, by
which the erythrocytes can escape only when the openings are
abnormally enlarged by the active work of the leucocytes. The
opinion that prevails at present, however, is that no pre-formed
stomata exist, and that the emigration proceeds by temporary
openings, excavated by the pseudopodia of the leucocytes at the
junction of the histological elements of the venous walls or capillary
endothelia. The erythrocytes, owing to the softness and elasticity
of, their protoplasm, pass readily (perhaps even passively) through
the openings excavated by the leucocytes, as through a network.

It is still doubtful if corpuscular extravasation (whether active,
as for the leucocytes, or passive, for the erythrocytes) is to be
regarded as a physiological phenomenon, exaggerated under
abnormal conditions of inflammatory irritation, or as an emphati-
cally pathological phenomenon.

E. Hering adopted the former opinion, on the strength
of the following experiment. He injected a finely pulverised
aniline pigment into the blood of an animal, and after some time
examined the hepatic lymph, when he found numerous leucocytes
as well as erythrocytes impregnated with pigment, but no free
granules of pigment in the lymph plasma. From this he con-
cluded that under normal conditions also certain leucocytes (and
possibly erythrocytes as well) migrate from the vascular system

VOL. I N

178 PHYSIOLOGY CHAP.

by diapedesis, and penetrate through the lacunae of the plasma
into the lymphatic system.

Be this as it may, it is certain that diapedesis proceeds •'
tumultuously during inflammatory irritation, and gives rise to the
phenomenon of suppuration at the focus of inflammation.

In order to complete the theory of corpuscular diapedesis we
must further inquire why the leucocytes become stationary and
adherent at the origin of the veins, and migrate from the vascular
system. A satisfactory answer to this question can only be
obtained from the interesting studies of Pfefier on Chemotaxis,
which were alluded to in Chap. III. (pp. 74-76).

Leber was the first to regard the migration of leucocytes as
a chemotactic phenomenon, caused by an attractive or directive
action exerted by the chemical products of the pyogenic or pus-
producing microbes on the leucocytes. He extracted from -the
culture of Staphylococous pyoyenes aureus a crystallisable substance,
which he termed phlogosiu, and observed that some time after the
introduction of a capillary tube filled with a solution of this
substance into the anterior chamber of the rabbit's eye, a mass of •
leucocytes migrated from the pericorneal vessels.

Lubarsch was able to show that living bacteria had a greater
attraction for frog's leucocytes than those previously killed by heat.

Massart and Bordet succeeded in showing that the same
leucocytes are attracted by liquid cultures of different microbes
(v. Fig. 19, p. 75, Stapliylococcus pyogenes albus), by inflammatory
exudates, and by certain nitrogenous or phosphorus-containing
waste products, e.g. leucin. They also discovered another im-
portant fact : if the leucocytes are narcotised in the total narcosis
of the animal by paraldehyde or chloroform, they are checked like
amoebae in their active movements, and all emigration that might
be going on from the vessels ceases entirely. This confirms the
idea that the migration of the leucocytes is a process dependent on
their excitability or amoeboid sensibility.

In microscopic observations of the circulation in .small vessels and
capillaries, the transparency of the richly vascular organs of certain
animals can be made use of. This is excellently seen in the frog's lung,
by Holmgren's method (v. Fig. 48, p. 173). After cm-arising the animal l>y
the subcutaneous injection of a few drops of 1 per cent curare (sufficient to
paralyse it) a lateral incision is made through the whole depth of the
body wall, a little below the anterior limb. The lung inflated with air
will usually protrude of itself from the opening. To avoid emptying the
lung, which is useless for observation in the collapsed state, Holmgren
employed a small •cannula, which is introduced through the glottis, and
attached by a ligature to the lower jaw. The end of the cannuJa has two
circular grooves in which is tied a bit of frog's intestine into which the
cannula had l>eeii introduced. Between the two grooves are two openings,
into which air is blown so as to distend the intestine drawn over it. This
dilates, and serves as a tampon, preventing the air of the lung from escaping
through the space between the cannula and the glottis. A small rubber tube
is fixed to the cannula, carrying at the other end a clip which is closed so

vi CIRCULATION OF BLOOD: ITS DISCOVEEY 179

soon as the lung lias readied the desired state of extension. To obviate tlie
inconvenience due to the convex surface of the organ, Holmgren invented a
little apparatus, which consists of a special frog-holder, on which the animal
can lie. It has an opening closed by a glass plate, above which a second
glass plate is fixed in a metal frame, which can be raised or lowered by a
screw. The lung, suitably inflated, is brought between these two plates, its
convex surface being flattened and adapted for observation by gentle pressure
of the upper plate.

Another admirable subject for the observation of the circulation, which
was used more particularly by Cohnlieim in his classical work on inflamma-
tion, is the frog's mesentery (v. Fig. 49, p. 176). The experiment is carried out
as follows : The curarised frog is laid 011 a cork plate, with a hole in its centre
to correspond with the aperture in the stage of the microscope, to which the
cork plate is fixed by clamps. Above the hole in the cork plate a ring, also
cut out of cork, is fixed by pins, the upper edge of which lias a depression
that serves to hold the bit of intestine fixed so as to stretch the mesentery.

A lateral incision now has to be made in the frog's abdomen, avoiding the
lateral vein, when a loop of intestine is carefully drawn out with forceps, and
laid in the depression of the cork ring, so that the stretched mesentery lies
taut over the aperture of the ring. This brings the part under examination
to a higher level than the abdominal wound, otherwise it would become
charged with blood and serum escaping from the wound.

The above ring is not required for observing the circulation in the
interdigital membrane or tongue of the frog, or in the tadpole's tail, etc., as
these can be simply fixed to the cork plate by pins. When the observation
is to be prolonged for any length of time, it is necessary to prevent the parts
from drying up, which is done by placing over them little strips of filter-
paper soaked in physiological salt solution. The same method, with greater
precautions in regard to moisture and temperature^ will -Serve for examining
the capillary circulation in warm-blooded animals, using, '>.</., the mesentery
of mouse, guinea-pig, etc.

BIBLIOGRAPHY

For the history of discovery of the Circulation of the Blood, the reader is

referred to the two following monographs, which comprise an enormous amount

of research in original texts, and a clear and impartial criticism of ancient and

modern contributions to the literature of this vexed question : —

G. CEHADINI. Rieerche storico-critiche intorno alia scoperta della circulazione

del sangue. Milan, Fratilli/Richiedei, 3876 (333 pp.). Difesa della mia

Memoria intorno alia scoperta della circula/done del sangue, contro 1' assalto

dei signori H. Tollin teologo in Magdeburg, e W. Preyer lisiologo in lena.

Con qualche nuovo appunto circa la storia della scoperta medesima. Genoa,

1876.

SlB MICHAEL FOSTEK. History of Physiology. Cambridge, 1901.
R. WILLIS. Preface to Sydenliain Edition of Harvey's Works. London, 1878.
M. ROTH. Andreas Vesalius Bruxelliensis. Berlin, 1902.

For discovery of Lymph Circulation the tine article in Lipsius may be
consulted : —

W. His. Uber die Entdeckuiig des Lymphsystems. Zeitschr. f. Anat. u.
Entwickelungsgeschichte, 1875.

For discovery of Corpuscular Diapedesi.s, a complete account will be found in
the following memoir : —

P. HEGER. Etude critique et exp. sur I'enrigration des globules de sang,
envisagee dans ses rapports avec I'inflammation. Brussels, H. Mauceaux,
1878 (116 pp.).

For Phagocytosis and Chemotropism of Leucocytes see : —

E. METSCHNIKOW. Leoons sur la pathologic comparee de I'inflammation. Paris,
1892.

CHAPTEE VII

MECHANICS OF THE HEART

CONTENTS. — 1. Description of cardiac cycle or revolution. 2. Changes of ex-
ternal form, of the internal cavity, of the position and volume of the heart in the
different phases of its activity. 3. Mechanism of semilunar valves. 4. Mechanism
of auriculo- ventricular valves. 5. Theory of so-called heart-sounds. 6. Variations
of pressure within the auricles and ventricles during the cardiac cycle. 7. The
diastolic aspiration ; various explanatory hypotheses. 8. Cardiac plethysniograms ;
theory of active diastole. 9. Cardiograms ; theory of heart-beats or impulses.
10. Other mechanical effects of cardiac activity. 11. Work done by the heart.
Bibliography.

THE continuous circulation of the blood from the arteries to the
veins through the capillaries demands, as its first indispensable
condition, a mechanism by means of which blood pressure is
maintained high in the arteries and low in the veins, so that there
is a considerable difference of pressure between the two parts
of the vascular system. This mechanism is represented by the
heart, which in its rhythmical movements drives as much blood
through the aorta and pulmonary artery during systole, as it
receives from the venae cavae and pulmonary veins during diastole.

I. When the movements of the exposed heart are observed in
the living animal, a series of phenomena, which are repeated at
regular intervals, is witnessed. Each such cycle of movements is
known as the cardiac cycle, or revolution. The duration of each
cycle is exactly equal to the time interval between any two
recognisable arterial pulses.

This interval may be divided into three periods : in the first
is the (normally synchronous) systole of the two auricles ; in the
second, the (normally synchronous) systole of the two ventricles ;
in the third, the pause or rest of the whole heart. For simplicity's
sake, the first may be termed pre-systole ; the second, systole ; the
third, peri-systole. The diastole of the auricles coincides with the
commencement of systole, the diastole of the ventricles with the
commencement of perisystole.

The words awToK-fj and diao-roXr/ from <ru-a-T^\\€iVj contrahere, and 5ia-<TTt\\eiv,
distrahere, were first used by Galen. The term peri-systole for the resting'
period of the heart as a whole was introduced by Riolan (Encheiridium

180

CHAP. VII

MECHANICS OF THE HEAET

181

anatomicum, 1649), that of pit-systole by Spring, 1860, who, however, intended
to describe an imaginary active dilatation of the ventricle, immediately
preceding systole.

Normally the duration of presystole is much shorter than
that of systole. With accelerated cardiac rhythm, i.e. when the
period of the cardiac cycle decreases, perisy'stole, more particularly,
shortens, and shows a tendency to disappear altogether ; the
duration of systole, on the other hand, is either unchanged
(•Ludwig), or shortens only
when there is an exag-
gerated acceleration of
rhythm (Donders).

Presystole consists in a
contraction of the mus-
cular walls of the auricles,
seen with the unaided eye
to be peristaltic ; this peri-
stalsis starts from the
extreme end of the veins
which open into the aur-
icle, is propagated in the
auricle from above down-
wards, and extends as far
as the auriculo- ventricular
groove. The presystolic
contraction diminishes the
cavity of the auricles in
every diameter, least, how-
ever, in the longitudinal
direction (Kiirschner).

The striated muscle
fibres with which the
veins are provided in the
vicinity of their openings
into the auricle, and the
arrangement of the mus-
cular fibres of which the
walls of the auricles con-
sist (Figs. 50, 51), account for the changes in diameter exhibited
in presystole.

In systole, the ventricles seem on simple inspection to contract
simultaneously at every point. Yet more delicate observation
shows that the contraction here also is peristaltic, commencing at
the auriculo-ventricular groove, when the presystolic movement
has reached its maximum, and spreading thence to the apex with
such velocity that the eye cannot follow it. Systole is accordingly
only a continuation of the presystolic contraction wave, which

FIG. 50. — Human heart dissected after boiling, to show
superficial muscular libres, seen anteriorly. (Allen
Thomson.) a', Aorta ; b', pulmonary artery cut short
close to semi lunar valves, to show anterior fibres of
auricles ; a, superficial layer of fibres of right ventricle ;
b, that of left ; c, c, anterior interventricular groove ; <t,
right auricle ; <l', its appendix, both showing chiefly
perpendicular fibres ; e, upper part of left auricle ;
between e and b' the transverse fibres, which, behind
the aorta, pass across both auricles ; e', appendix of
left auricle ; /, superior vena cava round which, near
the auricle, circular fibres aro seen ; g, g', right and left
pulmonary veins with circular bands of fibres surround-
ing them

182

PHYSIOLOGY

CHAP.

suffers a brief delay on reaching the auriculo-ventricular groove,
and is then propagated with extreme rapidity from base to apex
of the ventricles.

It. The changes exhibited in the three principal diameters of
the ventricles, and the modifications of the internal conformation
of the heart during systole, can be estimated by direct observation
(Harvey), by approximate measurements (Ludwig),and by recording
apparatus (Roy and Adaini). Not only the transverse diameter—
which no one contests — but the longitudinal diameter also, shorten

during systole ; the sagit-
tal or antero - posterior
diameter seems on the
other hand to lengthen
a little — although this
is contradicted by some
observers. It is certain
that during systole the
elliptical base of the
heart becomes almost
circular, and the apex,
which in rest is tilted to
the left, becomes perpen-
dicular to the centre of
the base, advancing to-
wards the thoracic wall.
The ventricles simul-
taneously undergo a
twist from left to right,
by which a portion of
the left ventricle wall
becomes visible, which

FIG. 51.— Posterior view of same preparation as in preced- during rest is COVCred by

the wall of the left lung.
That these changes
of form in the ventricles
during systole depend
essentially, like those of
the auricles during presystole, upon the specific structure of the
myocardium, is shown by the fact that the same changes of form
and diameter can be observed in the mammalian heart, when
excised and placed upon a flat surface (Ludwig).

The structure of the myocardium is so complicated that it
only lends itself to schematic representation, and not to exact
description. The more recent studies of Hesse and Krehl, follow-
ing on those of Ludwig and Henle, have, however, cleared up the
points of greatest physiological interest, which may now be briefly
summarised.

ing figure. (Allen Thomson.) a, Left ventricle ;" It, left
ventricle ; <; <•', posterior interventricular groove ; il, right
auricle ; c, left auricle ; /, superior vena cava ; g, g',
pulmonary veins cut short ; h, sinus of great coronary
vein covered by muscular fibres ; //', middle cardiac-
vein .joining coronary sinus ; i, infer.or vena cava ; i',
Eustachian valve.

VII

MECHANICS OF THE HEART

183

The external muscular layer of the myocardium is common
to both ventricles
(Figs. 50, 51, 52).
Its fibres take origin
in the fibrous ring
at the base of the
ventricle ; they de-
scend obliquely from
above downwards,
and after rejoining
the apex of the
heart most of them
form a vortex, sink-
ing deeper and fur-
nishing almost the
whole of the inner
layer of the left
ventricle, papillary
muscles, columnae
carneae and muscu-
lar fascia oi the FIG. 52.— Surface tlbres of ventricles of human heart from the front
nVinrrlna fori and below. (Reid.) a. Vortex of apex'; i>, bundle of fibres emerg-

ing from exterior of left ventricle at vortex a, and crossing lower

Of the mitral I)art of septum uninterruptedly. At d the surface fibres are
, „ somewhat interrupted.

valves, as first de-
scribed by Oehl. The fibres of the internal muscular layer of the

right ventricle, on the
contrary, originate in
the upper border of the
interventricular sep-
tum, and form numer-
ous reticulated, almost
transverse, trabeculae.
At different heights of
the ventricular cavity,
innumerable little
muscle bundles and
tendon fibres unite the
septum with the walls
of the ventricle, while

Fio. 53.— Section across middle third of a human heart fixed Other Separate bundles
in diastole. Seen in perspective. (Krehl.) The cavity of oGPf>nrl p« ™millnrv
the right ventricle shows a number of trabeculae, muscle dbCeilU <*b d,iy

muscles, to unite by
the chordae tendineae
with the tricuspid valve
(Fig. 53).

In the cavity, both of the left and of the right ventricle, two
parts of the internal wall can be distinguished, which are termed

bundles and tendinous filaments, which connect the walh
of the ventricle in every direction with the interventricular
septum. The cavity of the left ventricle is much simpler.
The figure a4so gives a clear idea of the difference in thick-
ness of the walls of the two ventricles.

184

PHYSIOLOGY

CHAP.

COD! arteriosi (lying beneath the orifices of the aorta and pulmonary
arteries); these present a smooth surface, destitute of reticular
trabeculae, and provided with stout bundles of longitudinal
muscles.

The far greater bulk of the walls of the left ventricle, in
comparison with those of the right, is especially due to the
presence of a third layer of muscle fibres, which can be isolated
with nitric acid; this dissolves the tendinous and connective
tissues, making it possible to separate the inner and outer coats of
muscle fibres. In this way an intermediate layer of fibres can be
isolated which are almost circular in direction and form a some-
what conical mass ; these do not end in tendons, but wind round

upon themselves, and belong ex-
clusively to the left ventricle
(Krehl : Fig. 54).

No less interesting than the
changes of external form are the
systolic changes within- the ven-
tricular cavities. To form an
adequate notion of these, it is
necessary to fix and harden two
human hearts, one in a state of
total systole, the other, as nearly
as possible of the same size, in a
state of maximum diastole (Krehl's

Fi«s. ;-,4.— Middle layer of muscular fibres, metftOCl>
destitute of tendons, from left ventricle of

human heart, after removing internal and Io obtain the dead heart fixed 111

external layers. The form of the heart is diastole, it must either not have entered
schematically indicated. J the natural •, ,. • . . L i ' j

size. (Krehl.) the state ol ngor mortis, or must already

have passed out of it. After carefully

removing the heart from the thorax, all the great vessels must be made
water-tight (by means of corks introduced into their lumen), with the excep-
tion of the pulmonary vein and the vena eava superior, into which two
glass tubes of the same calibre as that of the vessels must be introduced, and
fixed by ligatures. Through these tubes the heart is filled with water under
a hydrostatic pressure of 50-100 mm. of mercury. The water enters by the
'great veins into the auricles, and by the aorta into the coronary arteries, out
of which it filters slowly through the cai-diac walls. The heart is thus
thrown into acute diastole, which is more pronounced than in life, and
is left 6-8 hours in this state. It is then fixed with 96 per cent alcohol,
which is passed through it for 3 to 4 hours under the same pressure as that
used for the water. To complete the hardening, absolute is substituted for
the dilute alcohol, without any further pressure.

Fixation in systole is effected by Hesse's heat method. The freshly
extracted heart is placed for an hour in a solution of potassium bichromate
at 52° C., which throws it into a state of pronounced systole.

Total systole of the human heart can only be demonstrated on the heart
of a subject who has died suddenly, at the maximum of rigor mortis.

Dissociation of the cardiac fibres is easy after treatment with ordinary
nitric acid. This acid, however, shortens the muscle fibres, and throws the
heart into more or less complete systole. In order to dissect out the heart

VII

MECHANICS OF THE HEAET

185

in diastole, it is necessary to prepare it with the acid under a pressure of
60 nun. mercury. This may be a complete success, but often fails, owing to
the easy rupture of the heart, more particularly of the auricles. After
submitting it to the action of the acid for about three hours, the heart is laid
for several days in water, in which the connective tissue, softened by the
acid, partly dissolves, and the rest can be readily separated from the muscular
tissue. The muscle fibres can then be teased out without difficulty.

FIG. 55.— A, Section tli rough heart of a criminal, fixed in systole, at limit of lower third of ventricles.
A', Section through same heart, Ht limit of upper third. B, Section through heart of approxi-
mately the same size as the preceding, tixed in diastole, at same level as A. JJ', Section of
same heart, at level of A'. All four figures are diminished by half. (Krehl.)

The cavity of the left ventricle, seen in section, appears in
systole as an irregular, somewhat star-shaped fissure, the centre of
which corresponds with the conus arteriosus. This proves that
the left -ventricle is unable to empty itself completely, even in
maximal contraction, so that a small quantity of blood is left in
it, more especially in the space immediately behind the semilunar
valves of . the aorta. Its driving power depends mainly on the
middle layer, contraction of which must produce a lengthening
of the longitudinal diameter of the ventricle : this is, however,

186 PHYSIOLOGY CHAP.

checked by the contraction of the external and internal coats,
which compress the middle coat from above downwards. The
longitudinal diameter of the left ventricle thus remains almost
unaltered (Krehl).

The cavity of the right ventricle is reduced in the maximal
systole to a narrow space, which is curved towards the left ventricle
on account of the convexity of the septum (Fig. 55). O\ving to
the absence of a middle layer, the longitudinal diameter of the
right ventricle is bound to shorten, and contributes to the conical
shape assumed by the heart, the apex becoming almost ventrical
to the centre of the base. The numerous trabeculae with which
the inner layer of the right ventricle is provided, and which
connect its walls with the septum, must help to bring ventricle
and septum together, and produce an almost complete occlusion of
the cavity.

Besides changes of form we have to consider those of position
and volume, which are brought about in systole.

It is easy to see by direct observation of the exposed living
heart that the systolic shortening of its longitudinal diameter
occurs not by lifting the apex, but by dropping the base. Hay craft
(1891) demonstrated this on the closed thorax of cat and rabbit by
pushing needles into the heart, which acted as levers, their fulcrum
being in the wall of the thorax. The end of the needle fixed in
the base of the heart oscillated upwards at each systole, showing
that the base in which it was plunged had sunk. The needles
fixed lower down oscillated in a less degree. Lastly, if pushed
into the apex, the needle trembled but slightly, showing this to be
the point that undergoes least shifting in systole from above down-
wards, so that the shortening of the long diameter (which, as we
have shown, is due to the longitudinal fibres of the right ventricle)
is practically compensated by the downward movement of the
base.

The apex, however, presses a little on the thoracic wall, either
because the heart assumes a conical shape, or because the base
not only sinks during the emptying of the ventricle but is also
tilted a little more obliquely from the back forwards (Carlile and
Ludwig).

Along with the mechanical effects of the cardiac cycle it is
necessary, lastly, to consider the changes of volume produced in
the heart during this revolution. From what has already been
said it is evident that the volume of the heart diminishes during
systolic evacuation, and increases during perisystolic filling. It
is further apparent that the state of maximum evacuation and
minimum volume (which Ceradini proposes to call meiocardia)
coincides with the termination of systole, and that the moment of
maximal filling and maximal volume (auxocardia) coincides with
the close of perisystole.

vii MECHANICS OF THE HEAET 187

III. The active mechanical functions of the cardiac muscles
are intimately connected with the passive mechanical functions of
the semilunar and intracardiac valves, with which the arterial and
auriculo-ventricular orifices are respectively provided.

The semilunar valves are fibrous membranes, forming pockets
attached to the edges of the arterial orifices, their concavity being
turned upwards, and their curved free borders nearly always
provided with a nodule (corpus Arantii). These valves are regularly
arranged so that one segment corresponds with the posterior wall
of the aorta, and one with the anterior wall of the pulmonary
artery : the remaining two closing with the former and converging

v ' O O O

towards the anterior wall of the aorta, and the posterior wall of
the pulmonary artery.

Each segment at the place where it is attached to the arterial
orifice abuts on a dilatation in the artery, which is known as the
sinus Valsalvae.

Above the three reunited sinuses is the dilatation of the first
section of the two arteries, which is known as the bulbus
arteriosus. The aorta accordingly possesses one posterior and two
anterior lateral sinuses, a right and a left ; from each of these
arises a coronary artery, right and left. In the pulmonary artery
we have, on the contrary, one anterior and two posterior sinuses,
from which no arteries arise.

Acquaintance with the anatomical form of these valves suffices
to show that their physiological function can be no other than to
inhibit or moderate the reflux of blood from the arteries to the
ventricles in diastole, while they readily permit the efflux from
ventricles to arteries during systole. From Galen to Vesalius, and
from Vesalius to our own day, it has been held that the opening of
the semilunar valves was the effect of the torrent of blood rushing
from the ventricles at systole, and that their closing was due to
the regurgitatioii of blood from the artery to the ventricle at the
commencement of diastole : " nam obstaculum ne quid penitus
regurgitaret effingere fuit impossibile " (Vesalius). Supposing that in
systole the semilunar valves are completely raised, so that they are
applied to the walls of the sinus Valsalvae and occlude the openings
of the coronary arteries (Thebesius, Brlicke), or that they assume
the half-open position (Hamburger, Elidinger, Hyrtl), then at the
beginning of diastole a greater or less reflux of blood must be
postulated, to bring the valves back from the open, or half-open,
position to that of complete closure. Ceradini (1871) was the first
who demonstrated that the office of the semilunar valves was not
to moderate, but entirely to inhibit .the diastolic reflux.

He repeated and perfected certain experiments of llildinger in
direct observation of the valves, by applying a sort of speculum
cordis to the cadaveric heart, while imitating the cardiac systole
and diastole, and was able to show : —

188 PHYSIOLOGY CHAP.

1. That the position of elastic equilibrium of the semilunar
valves corresponds not with closure but with half -opening
(Fig. 56).

2. That during the systolic efflux the three sinuses of Valsalva
and the bulbus arteriosus dilate, and the semilunars assume and
maintain a half-opened position, with vibration of their free
borders, which therefore become blurred and give rise to a muffled
sound.

3. That at the cessation of systole (systolic dead point) the

valves close rapidly and then reopen,
if systole is not followed by diastole.

4. That when diastole follows
systole, the valves (which were
already closed at the systolic dead
point) extend towards the conus
arteriosus of the ventricle, forming
with their surfaces a tetrahedron,
with the point directed .upwards,
and emit a short sound which is of
higher pitch than the preceding.

From these results it is obvious
that the closing of the semilunars

Fio. 5(3. -Diagrammatic section, life size, jg the effect IlOt of Commencing
across sinus of art. pulmonaris of , _O

pig: constructed by Ceradini from diastole, but ol the close of Systole.

It is easy to see that no reflux is
possible under these conditions, since
the largest ami 'the least equilateral thcvalves are already closed at the

triangle that can be described by the ... ., , . •; , ,

three outlines (oCb, cDh, i>A<i) of the beginning oi diastole, and when

sinuses of Valsalva. The circle snr- 4- V, -,,,-. ,,,„ i^f/-* ,-vlr.ofirt f n-nnlnn Af\

rounding the smallest triangle repre- thrOWll intO elastic tension QO uuu

sents the projection of the constric- J^ggp Up this position of closure,
tion of the artery which divides , . .,

the sinoid from th« buibar portion. When, according to Ceradini s
*"aghj method, diastole is imitated by start-
lhe ing with the half-open position of
the valves, their closure is obtained

by a reflux, and the amount of fluid which under these condi-
tions regurgitates from artery to ventricle can be measured.
According to Ceradini, this would be considerable, amounting to a
seventh part of the flow that leaves the ventricle at systole. This
proves the importance of the pre-diastolic closure of the semilunar
valves, which normally prevents the loss of a considerable part of
the useful effect of the cardiac cycle.

In repeating the experiment, with Ceradini's apparatus, we
found several inconveniences, which we attempted to eliminate by
modifications indispensable to the demonstration of the play of the
valves before any large audience. Fig. 57 shows this improved
apparatus.

The theoretical explanation of the mechanism of the valves

VII

MECHANICS OF THE HEAET

189

as elucidated by Csradini, is founded on simple laws of hydro-
dynamics. The engineer Darcy (1857) demonstrated that fluids
passing through a tube are not under the same pressure, nor do
they move with the same velocity, in the different lines into which
the fluid cylinder can theoretically be analysed. The velocity is
greatest, the pressure lowest, in the axial threads ; in the peripheral
lines the velocity is
lowest and the pres-
sure greatest. This
law was confirmed a
year later by the re-
searches of Ludwig,
who employed new
and ingenious meth-
ods. In order to esti-
mate the different
velocities of the lines
of current, he em-
ployed opaque gran-
ules of lycopodium
powder, suspended in
water running through
a glass tube. To esti-
mate the difference in
pressure, he observed
the direction of the
current in a bent tube,
introduced into the
main tube in such a
way that one aperture
was just inside the
wall of that tube,
whilst the other pro-
jected farther towards
the axis of the current.
Ceradini further
showed that when a
piston was pushed in-
to a cylindrical glass
tube, held in the ver-
tical position, and half filled with water in which lycopodium
seeds are suspended, a centripetal eddy may be observed at the
base of the fluid cylinder depressed by the piston, and a centri-
fugal eddy at the other end. When the movement of the piston
ceases, the water cylinder breaks up momentarily into an inner
cylinder, which continues to move forward, and an outer ring,
which moves backward, united by a centripetal eddy.

FIG. 57. — Apparatus for demonstrating mechanism of semi-
lunar valves. B, liulb of art. pulmoriaris from heart of
recently killed pig; J's, sinus of Valsalva ; S, Riidinger's
speculum, closed at one end by a simple glass plate ; 1',
elastic rubber syringe, with which systole and diastole can
be imitated by hand ; fa, valve by which water can be
aspirated in diastole from a receiver, and then raised,
during systole, to the constant level of an upper vessel fixed
at a height which corresponds to the mean blood pressure
of the pulmonary artery in the living animal.

190 PHYSIOLOGY CHAP.

When water containing a lycopodium suspension is made to
circulate through a glass tube of small bore, which after a short
distance continues as one three or four times larger in diameter, it
is easy with a lens to see that there is a centripetal eddy at the
point where the tube suddenly widens, at which the lycopodium
granules at the base of the dilatation become central instead of
peripheral in position, and move towards the axis of the current,
where their velocity is greatly accelerated.

This experiment, which we have demonstrated for over forty
years, is well adapted to explain the mechanism of the semilunar
valves. Hesse and Krehl showed that in systole the arterial
orifices are reduced by the contraction of the longitudinal fibres,
which invest the inner wall of the coni arteriosi, to narrow fissures,
above which is the marked dilatation formed by the sinus Valsalvae
and the bulbi arteriosi. It is clear that the systolic current that
Hows out during systole and passes the contracting orifices must
make a centripetal vortex in the sinus Valsalvae, which hinders
the semilunar valves from opening completely, by tending to
throw them into the closed position. So long as the systolic
efflux continues, they can only vibrate round the half-opened
position ; but as soon as the efflux ceases, the centripetal vortex
continues, owing to the force acquired from the blood, and imme-
diately flings the valves into the position of closure. This
closure, which would only be temporary, becomes permanent from
the fact that the column of blood in the artery presses hard
against the valves directly diastole commences.

This mechanism of the opening and closing of the semilunar
valves furnishes the best and most rational explanation of the
many which have come under discussion. Tigerstedt has explicitly
adopted it in a recent synthetic review (1902). But he errone-
ously attributes the theory to Krehl, forgetting that it was clearly
formulated, and fully developed and illustrated, by Ceradini, in a
memoir republished in the German language as early as 1872.

IV. The mechanism of the auriculo- ventricular valves is
essentially similar in type to that of the semilunars; but con-
tains in addition other secondary features, which reinforce, and
at the same time complicate, the physiological function of the
valves.

The auriculo- ventricular valves (tricuspid and mitral) consist
of tubular membranes, which take origin in the fibrous rings at
the base of the ventricles, and divide into three (tricuspid) or two
(bicuspid or mitral) flaps (Fig. 58).

These flaps are united by tendinous cords (chordae tendineae)
—which are attached partially to the free border, partially to the
inferior surface of the valvular cusps — with the pillars formed by
the larger papillary muscles, or the coluinnae as they emerge from
the walls of the ventricle. The mitral valves are more solidly

VII

MECHANICS OF THE HEAET

191

constructed than the tricuspid, to meet the greater force they have
to encounter.

Kiirschner (1844) was the first to show that not a few of the
muscular fibres descend from the auricle to the superior or internal
surface of the valvular fibres. Oehl (1861) described small muscle
bundles which accompany the larger cords of the mitral valves.

IJ

Fio. 58. — A, Mitral valve of man, seen from below. The whole valvular ring has been spread out
in one plane, by a section through the median line of the great Hap. B, Tricuspid valve of
man, seen from below. The valvular ring has been cut at the junction of the antero-exterrial
and the internal flaps. P.u, Anterior papillary muscles; I'.p, posterior papillary muscles;
M.d, right flap of mitral valve ; M.g, left flap of mitral ; '/.<?.«, exterior and anterior flaps of
tricuspid ; T.e.p, exterior and posterior flaps of tricuspid ; T. i, interior flap of tricuspid ; L, 7.,
accessory tongue of valves ; A, great arch of free border of valves ; «, a, small arch of free
border of valves. I, Tendinous cords of first order ; II, tendinous cords of second order ; III,
tendinous cords of third order. (Marc See.)

Paladino (1876) described muscle fibres that are continued from
the base of the ventricle to the lower or internal surface of the
valves.

It is certain that without these valves, with which the auriculo-
ventricular orifices are provided, not .a single drop of blood could
pass from the ventricles to the arteries during systole ; it would
all be forced back into the auricles and veins, where the pressure is
very low.

Many theories are current about the function of these valves,

192 PHYSIOLOGY CHAP.

and are correct up to a certain point, but are all more or less
incomplete and inadequate. A complete theory can only be
obtained by weaving the several partial hypotheses together.

Prior to Lower (1679) there was no well-founded theory of the
mechanism of the auriculo- ventricular valves.

He formulated a theory of the passive systolic closure of these
valves by regurgitation of the blood, which had a great success.
Vieussens, Winslow, Haller, Senac, Magendie and others adopted
much the same opinion.

Meckel (1825) and Parchappe (1848) brought forward a very
different theory, and admitted an active systolic closure of the
auriculo-ventricular orifice by approximation of the folds of the
valves, which are kept tense by the papillary muscles connected
with them. This theory, too, found its' followers, including
Berard, Surmay, and See, the last of whom (reasoning from the
position of the valves in the hardened human heart) modified it in
several particulars, while retaining the main idea of an active
systolic closure. This theory, like the preceding, assumed a
certain reflux of blood from ventricle to auricle. The difference is,
that while on the former it was the reflux that closed the valves,
on the latter it is the movement of active closure of the valve that
drives back some at least of the blood contained in the conus
valvularis into the auricles.

Kiirschner (1840) was the first to ascribe an active function in
the expulsion of the blood to the cuspid valves. He admitted,
even if obscurely, that there must be a presystolic closure of the
valves, brought about more particularly by the contraction of the
auriculo- valvular fibres, which he described. At the beginning of
systole the valves are tense, and the chordae tendineae prevent
their reversal into the auricular cavity; with the progress of
systole, however, they are drawn down by the contraction of the
papillary muscles, and thus assist in emptying the ventricles in
the direction of the arteries.

Baumgarteu (1843) and Weber (1848) adopted these theories ;
and, in order to give a more satisfactory explanation of the pre-
systolic closure of the auriculo-ventricular orifices, they included
in their considerations the low specific gravity of the valves, in
consequence of which they open with a light pressure, as well as
the elastic tension into which the ventricles are thrown as
the effect of the presystolic wave. The same explanation was
adopted by Ludwig, Friedreich, Vierordt, and others in Germany.

In France, Kiiss, with the intention of further developing and
completing Kiirschner's theory, proposed a new hypothesis. He
assumed that a hollow cone was formed during systole, in conse-
quence of the contraction of the papillary muscles, which, as it
descends into the ventricular cavity, tends to bring the segments
of the valves into close proximity with the walls of the ventricle,

vii MECHANICS OF THE HEART 193

which is simultaneously brought nearer the valves by the efflux
of blood from the arteries. The effect of this mechanism would be
a negative pressure in the auricle during systole. But the idea
that the valves, when the heart is functioning normally, can form a
sort of hollow cone during systole, which presses into the cavity of
the ventricles like a stamp, is contradicted by the observations of
Krehl, as already cited.

In order to form a correct notion of the mechanism of the
auriculo-ventricular valves, it is indispensable to determine their
position during the entire period of perisystole, presystole, and
systole.

1. During perisystole, a centrifugal eddy of regurgitation must
be produced at the base of the ventricles by the kinetic energy of
the blood which is rushing from the auricles to the ventricles.
This vortex, directed from apex to base of the ventricle, is capable
of maintaining the folds of the valves (which are easily floated in
consequence of their light weight) in the half-open position.

2. During presystole, ventricular pressure is slightly increased,
owing to the wave of blood that is driven from auricle to ventricle.
The walls of the ventricle dilate passively, and are thrown into
elastic tension, while the wave of regurgitation from the centri-
fugal vortex increases, and the borders of the valvular folds tend
to approach, and take up a position approximating to closure.
The auriculo-valvular fibres of Kiirschner contract simultaneously,
which tends to shorten the valves and maintain them in the
upright position.

3. At the presystolic dead point there is a cessation of the
flow from auricle to ventricle, while the centrifugal vortex persists,
in consequence of the dynamic force acquired by the blood ; this
causes the valves to close with perfect apposition, not merely of
their borders, but also of a considerable portion of their internal or
superior surfaces.

4. At the commencement of systole the valves which are
already closed expand and vibrate, in consequence of the sudden
rise of ventricular pressure, and form an irregularly curved arch at
the level of the auriculo-ventricular orifice. This can be detected in
larger animals by passing the finger through an opening made in
the auricular appendix, as far as the auriculo-ventricular orifice
(Chauveau), and results from the varying lengths of the chordae
tendineae affixed to the inferior surface of the valvular folds
(Krehl, Fig. 59).

5. During the systolic evacuation of the ventricle, the auriculo-
ventricular orifice becomes more and more restricted until it almost
entirely closes. At the same time the valvular folds are drawn
forcibly onwards by the contraction of the papillary muscles, so
that increasingly larger portions of their inner or upper surface are
brought fully into contact, and deflected so as to become vertical.

VOL. i o

194 PHYSIOLOGY CHAP.

The synchronous contraction of the ventriculo- valvular fibres
augments their expulsive efficiency.

In this complex theory of the mechanism of the auriculo-
ventricular valves (which we have insisted on for thirty years),
the fact which is usually less generally accepted is that of
the presystolic closure of the venous orifices, which we hold to
be an indispensable condition of the normal exclusion from the
systole of all trace of reflux from ventricles to auricles. Chauveau,
while maintaining the theory of Klirschner, says expressly that
" les valvules auriculo-ventriculaires sont pendantes a la fin de la
systole auriculaire " (1876) ; without considering that if this pheno-
menon (which in his experiments is obviously the result of
weakened functions in the exposed heart of the horse, injured,

moreover, by the introduction of the
finger into the auricle) were normal,
there would, under physiological
conditions, be a pronounced reflux
of blood into the auricle at the be-
ginning of systole, synchronously
with the sharp rise of the valves.
For it is clear that at systole the
pressure increases not only in the
blood that is beneath the valves, but
also in that which lies along the axis
of the ostiuin, and which can flow
back freely so long as the valves are
not closed.

The mechanism of valvular

no. sp.-DiaKr.mi showing position of closure at the systolic dead point
auricuio-ventricuiar flaps of valves at is demonstrated by the following

commencement of systole, owing to . ^ , ,

puii of chordae tendinae. (Krehi.) experiment upon the excised heart

of man, pig, or other large mammal.

The cardiac cavity must be washed free of clot, and corks
fixed in the aorta and pulmonary artery, which are cut off short ;
the two auricular cavities are then opened freely from above,
and the margins of the openings attached to an iron ring upon
a support (Fig. 60) without tearing or deforming the base of
the ventricles. When the valves are normal, and rigor mortis
has passed off, it is only necessary to fill the two ventricles and
the funnel-shaped cavity formed by the walls of the auricles
with water, in order to see how the valves float up and assume
the half-open position. If presystole be now imitated, by
injecting a few c.c. of water with a powerful syringe, the nozzle
of which is directed towards the centre of the (right or left)
auricuio-ventricuiar ostium, a marked rise of the valvular flaps
will be seen, with such approximation of the borders that the
orifice is converted into a narrow slit, in consequence of the

VII

MECHANICS OF THE HEAET

195

centrifugal vortex and subsequent wave of regurgitation, which
drives the valves upward, and tends to close them. So soon as the

FIG. 60.— Apparatus to demonstrate presystolic closure of auriculo-ventricular valves. The two
figures represent the same normal heart of a young subject. The two arteries, aorta and
pulmonary, are divided near the orifices, and ligatured to corks. The walls of the auricle are
opened above and stitched to an iron ring clamped1 to a support. On tilling the cavity of the
heart with water, the auriculo-ventricular valves are seen to float into the semi-open position
(upper figure). After injection of a few c.c. of water in the direction of the axes of both
orifices, the valves temporarily assume the position of perfect closure (lower figure).

injection ceases, the flaps of the valves suddenly come together,
closing the ostium completely for the space of a few seconds.

196 PHYSIOLOGY CHAP.

This shows that the persistence of the centrifugal vortex produced
by the kinetic energy of the injected fluid, is of itself an adequate
mechanical condition to secure the perfect function of the valvular
apparatus, without the slightest regurgitation from ventricle to
auricle — even if we admitted that presystole is not immediately
succeeded by systole, biit that a period of intersystole constantly
intervenes, as has been proposed by Chauveau (infra, p. 201).

V. The acoustic phenomena which accompany the cycle or
cardiac revolution are intimately connected with the valvular
mechanism.

When the heart of a healthy person is auscultated directly
with the ear or with the stethoscope, two distinct murmurs are
heard, known to physicians as the cardiac sounds.

No one prior to Laennec (1819) had grasped the diagnostic
importance of these sounds. Harvey, whose panegyrists claim
that he was the first to describe them, confines himself to stating
that at the moment when the pulse is perceptible, a murmur can
simultaneously be heard in the chest. That is, he merely detected
the systolic sound, and rightly named it a murmur, since it has all
the properties of the latter, and can with difficulty be determined
as a musical tone.

Nothing is easier under physiological conditions than to dis-
tinguish the first from the second sound : the first is longer,
deeper, duller ; the second is shorter, sharper, clearer. The second
sound is followed by a long pause, while between the first and
second there is a lesser pause.

Since the first sound is systolic, i.e. it persists throughout
almost the entire systole, Laennec assumed that the first was
the effect of the systolic efflux from ventricles to arteries, the
second, of the diastolic afflux from auricles to ventricles, due to the
auricular systole or presystole.

It was easy for Turner (1829) to refute the second part of this
theory, by showing that the second or short sound, since it succeeds
immediately to the first or long sound, coincides with the commence-
ment only of ventricular diastole (or perisystole), and cannot there-
fore be the result of the auricular systole (or presystole).

Still more erroneous is Magendie's theory (1835), which
assumed that the first sound was the effect of the impact of the
apex of the heart against the thoracic wall in systole, and the
second of the impact of the base during presystole. The sounds
persist even after the thoracic cavity has been opened, and the
heart exposed.

The so-called valvular theory of cardiac sounds was first
formulated by Carswell and Kouanet (1832). Starting from -the
correct observation that the first sound is more acute in the region
of the ventricles, and the second in that of the arterial orifices;
they admitted that the first depended on the vibrations of the

vii MECHANICS OF THE HEAET 197

venous auriculo- ventricular valves, the second on the vibration of
the arterial or semilunar. They also succeeded in producing an
artificial sound in an excised aorta, by throwing the valves into
sudden tension.

Williams and the Dublin Committee of the British Association
(1835) undertook to test this theory, and confirmed by ingenious
experiments the part which referred to the second sound. They
noted that the second sound was abolished when the play of the
semilunar valves was impeded, as when the apex was cut, and the
blood prevented from issuing by the arteries. They, however,
found the valvular theory to be incorrect as regards the first
sound, observing that it persisted even when the heart was void of
blood and excised from the animal. Accordingly they postulated
a purely muscular origin for the first sound — a theory that was
taken up later on by Ludwig and Dogiel (1868), and confirmed by
numerous experiments.

Wollaston had already shown in 1810 that the contraction of
a muscle can produce a bruit. Ludwig further showed that
the muscles of the ventricle, which are interwoven in various
intricate ways, and form two cavities with trabeculated inner
surface, must be better able than skeletal muscles to generate a
bruit when suddenly thrown into tension.

The demonstration of the muscular theory does not, however,
exclude there being some truth in the valvular theory of the first
sound. Wintrich (1875), by means of Helmholtz' resonators,
succeeded in analysing the first sound, and recognised it to be the
result of two components : a deep sound (or rumble) of a muscular
character, and one or more sharp tones, depending not merely
upon the vibrations of the auriculo -ventricular, but also upon
those of the semilunar valves, demonstrated, as above, by
Ceradini.

Even with these additions, however, the theory of the sounds
of the heart was incomplete. Talma (1880) examined the valvular
theory from the standpoint of the laws of acoustic vibrations, and
objected that since the valves are immersed in a fiuid of lower
specific gravity than themselves, the sounds that are generated when
they are thrown into sudden tension must essentially depend upon
the vibrations of the blood, rather than on those of the valves.

Webster (1882), however, showed that Talma had overlooked
one fact, namely, that both the first and second sounds can be
resolved into several components, by the help of a resonator. He
attempted to prove that the effects of the vibrations of the semi-
lunars and also of the walls of the bulbi arteriosi, can be dis-
tinguished from the effects of the vibrations of the blood in the
second sound. To this we would add that the valvular vibrations
that contribute to the formation of the second sound, coincide, not
with the dosing of the valves, as is stated in every text-book, but

198 PHYSIOLOGY CHAP.

with the tension into which they are thrown after closure, when
the ventricular diastole commences.

In conclusion, we may admit the following points as
established :—

1. The systolic sound is essentially a muscular bruit, with
which higher tones are associated that depend on the vibrations of
the auric ulo- ventricular valves, the semilunars, and the mass of
the blood.

2. The post-systolic sound is the result of higher tones depending
on the vibration either of the semilunars and the bulbi arteriosi
when thrown into tension, or of the mass of the blood.

The importance of the heart-sounds, from a physiological stand-
point, consists in recognising them as the external signs of the
duration of the phases of the cardiac cycle, since there is good
reason for assuming that the commencement of the first sound
coincides with the commencement of systole, the commencement
of the second sound with the commencement of diastole ; and that
the interval between the first and second sounds represents the
duration of systole, the interval between the second and first, the
duration of perisystole plus presystole. We shall see how Edgren
has applied these criteria.

It is not the physiologist's task to make any profound examina-
tion of the pathological changes in the heart's sounds, or to go into
their great significance from the diagnostic and clinical standpoint.
But in so far as these changes are a proof, and a further illustration,
of physiological theory, the most general aspects of them may be
summed up in a few words.

Cardiac sounds under pathological conditions may be reinforced
or weakened, according as the heart's action is stronger or weaker
than in the normal state. The first may be a sign of hypertrophy,
the_second of degeneration, of the"" myocardium.

In auricular hypertrophy there may be a presystolic murmur,
immediately preceding the systolic, giving the effect of a duplica-
tion or abnormal lengthening of the first sound. On the other
hand there may be a real doubling of the second sound, when the
tension of the aortic seinilunar valves (which normally have to
bear a greater pressure) precedes that of the semilunars of the
pulmonary (which normally sustain less pressure) in marked
degree.

In stenosis of the orifices and in valvular insufficiency the
sounds are replaced by " blowing " murmurs, which are produced
by the vibrations of the blood as it passes through the narrowed
orifices or imperfectly closed valves.

In these can be distinguished : —

(a) Post-systolic murmurs, the diagnostic sign of insufficiency
of aortic or pulmonary semilunars, according as they are more
audible in the region of the origin of the aorta (right sternal

VII

MECHANICS OF THE HEART

199

border between the first costal and second intercostal space) or in
that of the pulmonary artery (left sternal border, at the level of
the second intercostal space). (Fig. 61, Ad and As.)

(b) Presystolic murmurs, the diagnostic sign of stenosis of the
right or left auriculo-ventricular orifice, according as it is more or
less audible in the region of the right ventricle (external border
of sternum at the level of the fourth intercostal space), or in the

FIG. 61.— Semi-diagrammatic figure of topography of the heart and its .relations with the lungs
and thorax. Vd, Auscultation point of right ventricle ; Vs, auscultation point of left
ventricle ; AJ, auscultation point of aorta ; Ax, auscultation point of pulmonary ; A, aorta ;
P, pulmonary artery ; cs, vena cava superior ; i, •/, innominate artery and vein ; .<?, *, subclavian
artery and vein ; c, c, carotid arteries ; g, g, jugular veins ; pe, dotted line to show limit of
lungs in inspiration ; pi, continuous line showing limit of lungs in expiration ; 1-10, 1st to
10th ribs.

region of the left ventricle (left mamillary line in the fourth or
fifth intercostal space). (Fig. 61, Vd and Vs.)

(c) Systolic murmurs, the diagnostic sign either of insufficiency
of the venous valves (bicuspid or tricuspid), or of stenosis of
the arterial orifices (aortic or pulmonary), according as it is
more conspicuous at one or other of these four points. Systolic
murmurs are distinguished from the preceding by their greater
accentuation, since they are produced by stronger vibrations, and
by the fact that the thoracic walls vibrate along with them

200

PHYSIOLOGY

CHAP.

(fremitus), as can be perceived on laying the hand upon the
precordial region.

The mechanical deficiencies of the heart can be compensated

rt ,C ^3 O ,C .U

ill ill

^ -c "3 H -S 5

Pi

l

^

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tu '-

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0 « "-or 5

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so that patients may live for many years. This compensation
depends essentially upon hypertrophy of the myocardium; more
particularly upon hypertrophy of the ventricles, in cases of
valvular insufficiency — upon hypertrophy of the auricles in arterial
stenosis.

vii MECHANICS OF THE HEART 201

VI. In order to comprehend the nature of the evacuation and
refilling of the heart, it is important to make an experimental
study of the oscillations of pressure within the auricles and the
ventricles, in presy stole, systole, and perisy stole.

These observations were first made by Chauveau and Marey
(1861) on the horse, by means of the so-called cardiographic
sound, in conjunction with a tambour and, lever writing upon
a rotating cylinder (Figs. 62 and 63). The modifications in
instrument and method made by Fick, von Frey, Hiirthle, Roy,
Fredericq, Bayliss and Starling, and Porter, have led to results
which differ in certain important points from those of the two
French investigators.

In the original researches of Chauveau and Marey, the tracings
of the oscillations of pressure in the right auricle were very
imperfect, owing possibly to insufficient sensibility of the elastic
ampulla introduced into
the said cavity. At the
Rome Congress (1894),
Chauveau corrected cer-
tain errors of Marey, on
the strength of new
cardiographic curves,
obtained from the horse

by means Of more per- FIG. OS. — Marey's tambour with writing lever (Verdin's

fppf PYnlnrat-nrv csnnnrk perfected type). «, Metal capsule closed by rubber

[eCD eXplOiatOry SOUnCtS. membrane, attached without tension to metal ring B.

Thptsp nVmprvuHnnej The aluminium disc fixed to the centre of the membrane

se oDSijrvauc (>arries a writing lever> Special contrivances make the

Were published in a instrument more or less sensitive by adjusting the initial
~r> . /_, orkr> position of the lever, and bringing the writing point nearer

Series Of memoirs (1899- to or farther from tiie surface of the moving drum.

1900), which seem to us

rather to indicate the unreliability of results obtained with the

cardiac sound, than to add to the known data of cardiac mechanism.

Let us examine the most important of these memoirs, that
entitled L' Inter systole du cceur (1900). This Chauveau calls a
phase of his cardiographic tracings, interpolated between presystole
and systole.

If the interpretation which he gives of this period, interposed
between the systole of the auricles and that of the ventricles, were
correct, it would involve a complete revolution in the fundamental
concepts of cardiac mechanism. To prove this, it is only necessary
to bear in mind the conclusions above stated in regard to the
function of the auriculo- ventricular valves.

These close at the end of presystole, so that they are
already shut at the beginning of systole. If, however, we admit
an intersystolic phase, then the said valves, not being kept
in the position of closure by rise of ventricular pressure, would
reopen, and thus render useless the entire apparatus described
above for closing them.

202 PHYSIOLOGY CHAP.

Chauveau, disregarding the conclusions of Ceradioi (whom he
does not mention), maintains on the ground of obscure experiments
and complicated arguments, that the contraction of the papillary
muscles of the ventricles occurs during his " intersystole," with the
object of disposing the flaps of the auriculo- ventricular valves in
such a manner that the systolic rise in ventricular pressure (which,
according to him, brings about the valvular closure) may impinge
principally not upon the axial but upon the parietal face of the
valves.

No long argument is required to demonstrate the impossi-
bility of this hypothetical doctrine. We know that the auriculo-
ventricular valves close at the termination of presystole. The

FIG. 64. — Tracings obtained by Chauveau from the horse, by his perfected cardiographic sound.
I, Oscillations of pressure in right auricle; II, oscillations of pressure in right ventricle;
r, return to abscissa; 1, period of auricular beat (contraction and relaxation); L>, period of
intersystole ; 3, period of ventricular beat (contraction only). This is succeeded by the period
of ventricular diastole, which Chauveau does not indicate.

supposed intersystolic contraction of the papillary muscles,
causing them to reopen, could not, even if it placed them in a
position unfavourable to the systolic reflux, entirely prevent it.
On the other hand, the researches of Eoy (1890) show that the
papillary muscles do not contract before the muscular walls of the
heart, but enter into tardy contraction, thus facilitating the almost
complete evacuation of the ventricles in systole.

Tigerstedt's interpretation of Chauveau's intersystole, in the
fourth edition of his Physiologic des Menschen, seems no less
impossible. He thinks it depends on the elastic reaction of the
walls of the ventricles, which are passively distended in auricular
systole, and which occurs only in cases in which the termination
of the latter and the commencement of the ventricular systole are
separated by a considerable time interval. It is, in fact, sufficient
to look at one of Chauveau's curves, especially that of the internal

viz MECHANICS OF THE HEART 203

pressure of the auricle and right ventricle, which he gives as
typical (Fig. 64), to see that the intersystole does not follow
immediately upon simple systole, but on the complete pulsation of
the auricle (auricular systole and diastole).

Since, however, the intersystole coincides with a sharp rise of
pressure in the auricle, and since the presence of a sound intro-
duced between the flaps of the valves may give rise to a slight
reflux of blood from ventricle to auricle, it seems probable that
the intersystole depends precisely upon this slight reflux, coincident
with the initiation of ventricular systole.

It is evident from these data that the " intersystolic phase " of
Chauveau's tracings represents no real fact, occurring during the
normal cycle of cardiac movement, but is in all probability an
artefact, coincident with the period of latent systole, artificially
prolonged by the presence of the exploring sound in the atiriculo-
ventricular orifice.

But if this point in Chauveau's tracings is difficult to interpret,
another feature offers far more insuperable obstacles, i.e. that part
of the pressure curve in the auricle which corresponds to the
ventricular diastole, which Chauveau passes over, keeping silence
on the subject.

At that period there is in Chauveau's curves an incomprehensible
rise of auricular pressure. Now the observations of all other
experimenters, carried out by different methods, more reliable than
the sound, have, without exception, resulted in showing a negative
pressure in the ventricle during the primary phase of diastole.
Since in diastole, when the cuspid valves are open, the auricle and
ventricle form a single cavity, it is evident that the negative
pressure existing in the ventricle must be propagated to the
auricle also.

More interesting and more probable, on account of their
simplicity, are the researches carried out by numerous experi-
menters on the venous pulse of the cava and jugular veins, either
in man or in animals, which throw light on the mode in which the
right heart is filled and emptied.

Among the authors who have more recently been engaged on
this subject are Mackenzie (1902), Beccari (1903), Wenckebach
(1906), Fredericq (1907). They have recorded tracings of the
venous pulse (phlebogram) with a simultaneous record of the
cardiac pulse (cardiogram), or of the radial artery (radiogram).

In nearly all healthy people, in the horizontal supine position,
with head and neck a little lower than the body, it is possible to
detect with the eye the pulsation at the base of the neck, and to
take a tracing of it, by means of a sufficiently sensitive exploring
tympanum. In the stage of convalescence from diseases, accom-
panied, as in jaundice, by weakening of the heart-beat, it is easy
to obtain fairly clear phlebograms, which in their elevations and

204 PHYSIOLOGY CHAP.

depressions faithfully reflect the phases of activity of the right
heart.

The phlebograms made by Wenckebach present three elevations
and three depressions as shown in Fig. 65.

Elevation (a) coincides with presystole, and expresses the
temporary arrest of the venous current (perhaps its partial reflux
also) during the contraction of the right auricle. The second rise
(0) corresponds with systole and depends, according to Mackenzie
and Wenckebach, on the mechanical transmission of the carotid
pulse beneath the vein that is being explored. This is rightly

FKJ. 0.0. — Tracings of oscillations of pressure in jugular vein (phlebograms) recorded with a fairly
sensitive exploring tambour, applied to the base of the neck in a youth of 23, recovering
from catarrhal jaundice (Wenckebach). Sphygmograms from radial artery simultaneously
recorded with the phlebograms. Time marked in .,'n". The points of return marked on the
tracings divide the period of pulsation into the five intervals described in the text.

contested by Fredericq, on the strength of his researches on dogs,
from which he proved that the rise (c) which accompanies the
beginning of systole is due to the closure movement of the
tricuspid valve. (Better expressed as, due to the projection
towards the auricle of the said valve, already closed at the
termination of presystole.) The third rise (v) coincides with the
tension of the semilunar valves already closed at the termination
of systole, and probably depends upon the impulse received by the
right auricle in the dilatation of the ostiuin and arterial bulb in
consequence of the wave of rebound which occurs at the com-
mencement of diastole.

The depressions of the phlebograms are more interesting to
consider, i.e. the two negative phases of the venous pressure. The
first (x), from the apex of (c) to the base of (v), coincides with
the phaqfl nf ayatolic emptying of the ventricles, and is due to
the sinking of the base of the ventricle by which the a-nrimiiar

cavity hftftomflfl fi^ftrt, and flTflrp.isfts a. marifftirl fl.spirfl.t,irm upon the
veins. The second negative phase (y} coincides with diastole, and
depends, according to Wenckebach, on the fact that during

VII

MECHANICS OF THE HEART

205

ventricular relaxation the blood can flow freely from the vein to
the auricle, from the auricle to the ventricle, by the negative
pressure or aspiration which this exerts during the said phase.

L. Fredericq, in his studies on
dogs (in relation to cardiography
of the heart and the venous
pulse, 1890-1907), insisted on the
virtual identity of the phlebo-
grams with the tracings of the
variations of blood pressure with-
in the right auricle, which he
obtained with open thorax, on
putting this cavity into direct
communication with a sensitive
sphygmoscope (Fig. 66).

To obtain an idea of the in-
dividual phases of the cardiac cycle and the oscillations of pressure
within the auricles, ventricles, and large arteries, we may avail

FIG. i)0. — Marey's sphygmoscope, which acts as
an elastic manometer in connection with
a tambour. It consists of a cylindrical
glass tube, closed at both ends by rubber
stoppers with a hole through the centre
of which come two glass tubes. An elastic-
cap is slipped over the right-hand stopper,
filled with an anticoagulant solution, and
connected with a blood-vessel. The cap
reacts to each rise and fall of pressure, by
expanding or contracting. The tube on the
left-hand side conveys these movements to
the tambour.

FIG. 67. — Diagram of cardiac cycle or revolution. The three curves reproduce the tracings of
oscillations of pressure obtained simultaneously from the left auricle, left ventricle, and
aorta of the dog, by Fredericq's method. The duration of the different phases of the cycle,
and the time at which the heart-sounds are perceptible, are marked on the abscissae ; the
intracardiac and aortic pressures in mrn. Hg, upon, the ordinates.

ourselves of a diagram constructed from the data provided by the
work of Fredericq, which agree fundamentally with those admitted
by all competent physiologists who have occupied themselves with
the mechanics of the heart (Fig. 67).

206 PHYSIOLOGY CHAP.

The diagram is so clear that a detailed description is super-
fluous. As appears in the figure, during presystole (which lasts
for about the sixth part of the time of the internal revolution)
there is a slight rise in auricular pressure which is transmitted to
the ventricle also, and which, as we shall see, effects the perfect
closure of the venous valve at the presystolic dead point.

In systole (which lasts two and a half times longer than pre-
systole) two periods must be distinguished ; the first, which is
short, termed the period of tension or latent systole ; the second,
somewhat longer, that of efflux, or systolic evacuation.

The first corresponds to the time necessary for the ventricular
pressure to reach and exceed the level of aortic pressure, in order
to determine the opening of the seniilunars.

With the sharp rise of ventricular pressure, there is a simul-
taneous rise of auricular pressure, determined by the tension and
upward propulsion of the cuspid valves.

The duration of this period in the horse is, according to Marey, Ol " ;
Hiirthle, on the contrary, finds it to be for dog O02-O04 ", and Fredericq con-
firms this last figure. For man the data vary considerably. Marey, Rive,
Landois, Edgren give figures oscillating between O'l " and O073", 'Grunmach
indicates a value of OO7", Keyti 0'054". Hiirthle, on the ground of his
researches on the dog, calculates the period of tension as equal to 0*03 " for
man, a figure which is certainly too high.

The second systolic period coincides with the rise of aortic
pressure (arterial pulse), the final elevation of ventricular pressure
which is then arrested in a kind of plateau, and a sudden drop of
auricular pressure, until it falls below zero, after which there is
again a slow but progressive rise.

Physiologists have long disputed over that portion of the curve of intra-
ventricular pressure which is known as the systolic plateau, and corresponds
to the ventricular efflux. While the tracings obtained by Cliauveau and
Marey in 1863 on the horse, and all the subsequent publications of Chanveau,
show an almost horizontal tract between the rapidly ascending (systolic), and
the corresponding and rapidly descending (diastolic), portions, many authors
maintain that the curve which represents the internal pressure of the
ventricle is composed solely of a rapidly rising, followed by a correspondingly
'rapidly falling portion ; they deny the existence of the systolic plateau. This
point has recently been 'taken up again by various authors, both English and
American, among whom are Bayliss, Starling, and Porter. They have intro-
duced important technical alterations in the method, which tend to exclude
instrumental inertia.

Bayliss and Starling employed a manometer containing a solution of
magnesium sulphate, one arm of which is open, and connected with the
cavity of the ventricle by means of an open sound, while the other arm
consists of a capillary tube sealed in the flame and containing air. This
small volume of air becomes more or less compressed by the liquid in the
manometer, owing to the pressure transmitted to it from the ventricle. The
degree of compression of the air column is registered by the displacement of
the shadow of the meniscus of the liquid column, which is projected on to a
rotating cylinder covered with sensitive paper.

Porter invented a method with the same object, but too complicated to be

vii MECHANICS OF THE HEAET 207

given here. Both his results and those of Bayliss and Starling confirm the
statement that the curve of intraventricular pressure presents a true systolic
plateau during the efflux of blood from the heart. This important feature
of the cardiac function seems, therefore, to be definitely established.

In perisy stole, too, it is possible to distinguish two periods ;
the one shorter, of active diastole, the other more prolonged, of
passive diastole or rest of the whole heart. During the former,
pressure falls suddenly both in ventricle and auricle, and becomes
negative, thus permitting the
active refilling of the heart by
aspiration of blood from the veins.
During the second, the negative
pressure rises again slowly in the
ventricle and auricle, until at
the beginning of presystole it
approximates to the zero line:
this represents the period of
passive filling of the heart, caused
by the vis a tevyo of the venous
blood stream, and the negative
pressure in the thoracic cavity,
when the experiment is con-
ducted with the closed thorax.

The elastic ampullae and
sphygmoscopes of Chauveau and
Marey are instruments well
adapted for obtaining tracings of
the form of the rapid oscillations
of pressure that occur within the

L -, . ., , . , FIG. (58. — Ludwigs mercury manometer (Xirn-

during the Cardiac Cycle, mermann's type). The float seen on the right

tVm\7 QVA innrtormoto fn rlo consists of a tine steel rod terminating at the

tney aie inadequate DO lower extremity m a pointed ivory cone,

termine the absolute value of wh]ch, <^)S into the column of mercury,

and at the upper extremity m a glass pen
the intraCardiaC preSSlire. Ihe tilled with ink, which traces the variations

best method for determining the %£?*«
maximum to which the pressure

in the cavities may rise, and the minimum to which it may fall, is
that of Goltz and Gaule (1878), which was also employed by De
Jager (1883), and consists in fitting to the recording mercury
manometer (Fig. 68) a valvular apparatus which closes when the
pressure falls, and opens again when it rises, or vice versa, so that
the manometer serves as a maximum or minimum manometer.
When connected with a cavity of the dog's heart by means of an
open sound, the column of the manometer will rise at each systole
to a given maximal height, after which it traces a horizontal
line (maximum manometer) ; or falls at each diastole to a cer-
tain minimum, after which it remains stationary (minimum
manometer).

208 PHYSIOLOGY CHAP.

The highest figures for cardiac pressure were obtained by I)e
Jager, who employed a maximum manometer and a sound of wide
calibre, on large dogs. He found in three experimental series : —

T. II. III.

In left ventricle .... 235 174 111 mm. Hg.

In aortci 212 162 158 „

In right ventricle. ... 28 44 72 „

These values are probably below the normal, since it cannot be
supposed that the introduction of a sound into the cavity of the
heart produces no disturbance of the systolic function.

It would be more interesting to determine the exact relation
between the maximal pressure of the right and that of the left
ventricle, since these must harmonise with the different strengths
of the muscular walls of both ventricles, and with the different
resistances which the two vascular systems (aortic and pulmonary)
present. The experimental data so far obtained have not, how-
ever, led to any concordant results. On an average it may be
assumed that the pressure in the right ventricle and pulmonary
artery is to that of the left ventricle and aorta as 1 : 2'5, or 1 : 3
(Goltz and Gaule, Colin, Beutner).

VII. The absolute values of negative intracardiac pressure
obtained with the minimum manometer are linked with the question
so much discussed in the last quarter of last century, i.e. the
determination of the mechanical factors by which the filling of
the ventricle during diastole is effected.

The theory supported by Harvey and Haller, to the effect that
the diastolic filling of the heart occurs quite passively, from the
wave of blood which rushes from auricle to ventricle in presy stole,
was for a long while accepted almost unanimously by physiologists.
The opposite theory, by which the heart acts as an aspirating pump
in diastole and as a pressure pump in systole, is, however, still
older, since it was formulated by Erisistratus and Galen, and
maintained at a later period by Vesalius, Bichat, Spreiigel, and
Magendie, without indeed finding any large number of adherents.

In 1871 we revived the theory of diastolic activity, on the
strength of certain rudimentary experiments, which may be
described as follows : —

(a) When in a dog with opened thorax a trocar is intro-
duced through the apex into the interior of one of the ventricles,
and a horizontal glass tube, open at the end, is attached to the
cannula, a jet of blood can be seen in the tube at each systole,
which recedes at each diastole.

(6) If the pressor effect of the presystole is impeded by seizing
the walls of the auricle with a forceps, the diastolic aspiration
increases conspicuously.

(c) If in consequence of vagus excitation, the heart's move-

vii MECHANICS OF THE HEAKT 209

ments are retarded, the diastolic aspiration increases so much that
the tube connected with the ventricle is emptied.

(d) If the hollow of the pericardial chamber is filled with milk,
and connected with a horizontal glass tube, containing a fluid to
serve as index, the total volume of the heart will be found to
increase during diastole, while with gentle stimulation of the
vagus this diastolic increase of volume is still further augmented.
This phenomenon is not necessarily connected with slowing of the
heart's action, since the same thing can be seen in the frog with
no appreciable changes in systolic frequency. (Coats.)

The conclusions we deduced from this and other facts had the
rare fortune of being confirmed by more complete and decisive
experiments. A. Tick (1873) showed by means of the metal
manometer, which he connected up with the right or left ventricle
of the dog (by a sound introduced through the jugular vein or
carotid), that pressure sinks below the zero line during diastole.
Goltz and Gaule (1878) endeavoured with their minimum mano-
meter to determine the absolute value of the negative diastolic
pressure with open thorax, and found that it may amount to
- 320 mm. of water in the left, and - 25 mm. in the right ventricle,
and diminishes progressively with the weakening of systole, i.e. in
proportion as the systolic evacuation becomes less complete. The
values obtained by De Jager by the same methods were higher :
he found a negative pressure that may amount to - 38 mm. Hg.
in the left, and - 6 mm. Hg. in the right ventricle. Values
approximating very closely to these were obtained by other
workers, e.g. Kolleston, v. Frey, and Krehl (1890), with the elastic
manometer, both with closed and with open thorax.

It was Stefani, however, who directly undertook the task of
experimentally checking, one by one, the propositions which
we had formulated in 1871, and repeated with certain altera-
tions in 1874 and 1876. In a series of interesting memoirs (1877-
1891) he placed on a firm experimental basis that same doctrine
of the activity of cardiac diastole which we had preached for
many years with ever-growing conviction, adding many new
arguments in its favour.

It is essential to the comprehension of this theory to premise that
the thesis of active diastole may be considered from two different
points of view. The diastole may be considered active in a purely
mechanical sense, viz. that the refilling of the ventricles during
the first period of perisystole is the effect not of the vis a tergo of
the blood descending from the auricles into the ventricles, but of
the aspiration developed by the latter during that interval. The
expression active can, however, also be employed in a strict
physiological sense, viz. that the diastole is controlled and regulated
the action of the vagus. Let us first consider the mechanical
aspect.

VOL. i p

210 PHYSIOLOGY CHAP. •

We have already seen that two periods can be detected in the
course of a cardiac revolution, during which the heart develops a
negative pressure and exercises aspiration upon the blood issuing f
from the veins : there is a moment of systolic and a moment of
diastolic aspiration (see Fig. 67). The former is confined to the
auricles ; the latter extends both to auricles and ventricles.

When systolic aspiration (as in Fredericq's experiments cited
above) takes place with the opened thorax, it must depend on the
sudden sinking of the base of the heart in the first period of
systolic efflux, which increases the capacity of the diastolic auricle.
This is. the explanation given by Purkinje (1843), by Nega (1851),
and more recently by Chauveau and Lefevre, as well as Fredericq.
This aspiration of the auricles has nothing to do with diastolic
activity ; it is caused by the systole of the ventricle, which works
simultaneously as a pressure pump against the arteries, and as an
aspirating pump against the auricles and veins.

The diastolic aspiration, on the contrary, which coincides with
the first period of perisystole, and spreads from the ventricles to the
auricles and adjacent veins, does really represent energy developed
by the ventricles during diastole. The mechanical effect of
diastole is indeed very small as compared with the mechanical
effect of systole ; but in any case it is sufficient to defend the
opinion that the ventricles are active in the first period of peri-
systole, and dilate by aspiration, not by the vis a tergo of the
blood rushing in from the auricles. The little frog heart is capable
in its diastolic distension of overcoming a resistance equal to
15-20 mm. of water (Mosso and Pagliani) ; the heart of a dog can
dilate, even when pressure is put upon its outer surface, in excess
by 20-30 cm. of water of that to which its inner surface is sub-
mitted (Stefani).

Various hypotheses have been put forward to explain the
diastolic aspiration, which may be rapidly summarised : —

(a) The pressure within the thoracic cavity is negative even
in the expiratory position of the lungs, and becomes more strongly
negative during inspiration.

As early as 1853 Bonders pointed out the importance of this
mechanical factor, which serves to facilitate the course of the
blood in the intrathoracic veins and the diastolic filling of the
heart by aspiration. Yet this does not adequately explain the
diastolic aspiration, which can be demonstrated even with the
open thorax. Nor does it explain the cardiac aspiration visible
with closed thorax, since this is greater in the left than in the right
ventricle, and in the latter again than in the auricles, where it
should, in consequence of the ready extensibility of the auricular
walls, be greatest.

(5) In 1855 Briicke revived the theory of the auto-regulation
gf the heart, basing it on the same arguments as already brought

vii MECHANICS OF THE HEAET 211

forward by Thebesius (1708). According to this theory the
coronary arteries empty during systole and expand in diastole,
either because in systole the orifices of the coronary vessels are
closed by the raising of the semilunar valves and their application
to the walls of the sinus Valsalvae, or because the finer ramifica-
tions and capillaries of the coronary vessels are closed or drawn
together by the contraction of the myocardium.

The first argument was refuted by Lancisi (1728) in opposition
to Thebesius, and again, with more cogent reasoning, by Hyrtl
against Briicke, and it is, in the light of all that is known about
the mechanism of the semilunar valves, entirely erroneous.
Neither Hyrtl nor Ceradini, however, found any valid objection to
the second argument, which is to-day regarded as established by
the experiments of Klug and Rebate!, and the more recent work
of Porter and Hyde. Klug succeeded in the living animal in
ligaturing one heart in systole and another in diastole. On
microscopic examination he found that the superficial vessels were
full of blood in the first heart, while the deeper ones were almost
empty : in the second, all the coronary vessels were turgid.
Rebatel, using Chauveau's haemodromograph (see next chapter),
succeeded in obtaining a tracing of the pressure and velocity of
flow in the coronary arteries of the horse. He found that pressure
and velocity increase in the first period of systole ; that at a
second period, pressure increases and velocity decreases until it
becomes negative (arrest and recession of blood into the coronary
vessels) ; finally, that at the beginning of diastole there is accelera-
tion of velocity without increase of pressure. Porter was able to
convince himself by an admirable method, in the dog, that the
intramuscular branches of the coronary vessels were compressed
and emptied by the contraction of the myocardium, and that this
systolic evacuation assisted the streaming of the blood through the
walls of the heart when the myocardium relaxed, owing to the
diminished resistance offered by the slack and empty vessels to the
blood-stream. Lastly, Hyde studied the effects of the various
distensions of the ventricular cavities on the isolated cat's heart,
by suffusing blood through the coronary vessels at constant
pressure. He determined that whether the heart was at rest or
beating, the flow of blood diminished when the heart was more
extended, i.e. when circulation in the coronary arteries was
impeded.

But even if the automatic regulation of the heart, in so far as
systole impedes the circulation in the coronary arteries by com-
pressing them, while diastole facilitates the filling of the coronaries,
be accepted, it does not necessarily follow, as assumed by Briicke,
that there is in diastole a kind of erection of the cardiac walls
which tends to produce a negative pressure in the cavity, and to
facilitate its filling. It is true that Bonders and Albini claim,

212 PHYSIOLOGY CHAP.

with the help of a manometer communicating with a cavity in the
dead heart, to have observed a diminution of pressure, so soon as
they injected the walls of the heart from the coronary artery ; but
Oehl, on repeating the experiment, found exactly the contrary, i.e.
increase of pressure within the heart, so soon as the pressure was
strongly augmented in the coronary vessels.

This contradiction between the results of such experienced
experimenters shows, without reference to other arguments that
might be brought forward, and have been adduced by Oehl, that
Briicke's theory is quite inadequate to explain diastolic aspiration.

(c) Gaule (1886) suggested 'that the negative pressure in the
ventricle, which he determined with Goltz by means of a minimum
manometer, depended on the dilatation of the aortic orifice after
closure of the semilunar valves at the commencement of diastole.
Since the aorta is connected with the fibrous ring from which the
muscle fibres of the ventricle originate, it follows that the ventri-
cular cavity must dilate at the moment when the ring becomes
distended, producing a negative pressure. Both Minck (1890) and
Krehl (1891) proposed this hypothesis.

But even if it is undeniable that when the aortic orifice dilates,
the conus arteriosus which lies below, and is in a certain sense one
with it, dilates also, it does not follow that this condition occurs at
the beginning of diastole, and can explain the diastolic aspiration.
The maximum of pressure and dilatation in the bulbus aortae
must obviously be reached during the systolic efflux, and not at
the commencement of diastole. " At the first outpouring of the
systolic stream," as Ceradini says, " the bulbous portion of the
artery (aorta or pulmonary) dilates, so that each of its diameters
increases by about one-fifth ; the walls of the sinus Valsalvae are
better able to resist the impact, yet they, too, show a very consider-
able dilatation, owing to the distension of the valvular membranes,
whose free borders become straight at the first onset."

At the commencement of diastole, on the other hand, the
valves are already closed and bulge towards the conus arteriosus,
so as to diminish its capacity, presenting with their united margins
'the figure of the sides of a tetrahedron, the apex of which, built
up of the three coincident corpora Arantii, falls on its vertical
axis, and is inverted downward towards the hollow of the
conus arteriosus. "The insertion of the valvular borders," says
Ceradini, " are externally recognisable at the points of contact of
the ellipsoid formed by the sinus Valsalvae, by a conspicuous
depression, which is visible at the arterial wall at the first onset of
diastole, in consequence of the sudden distension of the semilunar
membranes."

Gaule's explanation accordingly fails to explain the diastolic
aspiration.

(d} The oldest hypothesis in explanation of the active diastole

vii MECHANICS OF THE HEAET 213

is that of Galen, who distinguished in the heart predominatingly
transverse, and predominatingly longitudinal fibres. In systole
the former contract, and the cavities of the heart are restricted ;
in diastole the latter contract, and the cavities are dilated.
Vesalius assumed much the same position, which had many
adherents both before and after Harvey, who denied that there was
diastolic activity. In 1861 it was revived (with slight modifica-
tions) by Spring. He supposed that the more or less longitudinal
fibres of the heart contracted somewhat before the transverse, thus
producing an active dilatation of the ventricular cavities before
the commencement of systole proper. This theory is, however,
put out of court by the fact that aspiration is determined not at
the pre-systolic but at the post-systolic moment.

Brachet (1815) maintained that active diastole depended on
hypothetical radial fibres, coursing from endocardium to peri-
cardium, which he believed himself able to demonstrate on the
heart of man, horse, and ox. According to this author, the walls
of the heart exhibit a considerable thickening in systole ; in
diastole the radial transverse fibres contract and reduce the
diameter of the walls of the heart, thus augmenting its capacity.
Most French writers of the first half of last century, e.g. Filhos
(1855), Choriol (1841), upheld this view, which, however, was
strongly disputed by Parchappe and Berard. In order to prove
this position it would be necessary to show that the two kinds of
fibres in cardiac muscle contracted successively and not simul-
taneously, as we must assume.

In a corrected and amended form the hypothesis of Galen, of
Brachet, and of Spring was revived by Krehl (1891). He assumes
an unequal (i.e. a non-sychronous) relaxation of the different
muscular layers of the heart, and held that the expulsor muscle
(intermediate layer of the left ventricle) relaxed earlier than the
longitudinal fibres of the internal layer, so that the latter, being
no longer compressed, enabled the walls of the ventricle to move
apart. He founds his position upon the experiment of Eoy (1890),
who succeeded in obtaining simultaneous tracings of the contraction
of the walls of the heart, and of the papillary muscles, and demon-
strated that these last contract later and relax earlier. This
fact, however, contradicts Krehl's view, according to which the
papillary muscles relax later than the walls of the ventricle.
Among Krehl's various hypotheses this appears to us the least
acceptable.

(e) The most universally accepted view of diastolic aspiration
is that it depends on the elastic reaction of the myocardium,
thrown into tension at systole. This is the theory which was
clearly expressed in 1838 by Magendie, when he compared diastole
to the dilatation of a rubber tube when released i'rom compression.
L, Fick (1849) was the first to prove this on the dead heart in

214 PHYSIOLOGY CHAP.

which he imitated systole by compressing it with his hand, and
diastole by simply releasing it. On sinking the heart in a vessel
of water, he was able at each compression to drive a jet of fluid
through the arteries, a proof that, after releasing the ventricles,
the internal cavity distended and filled with water. It was
objected to this experiment that the phenomenon might be due
to cadaveric rigidity of the heart : Goltz and Gaule, however,
regarded the elastic reaction of the heart at the commencement
of diastole as proved by their experiments with the minimum
manometer.

The same view was taken by De Jager, who met every con-
ceivable objection to the theory that the filling of the heart at the
commencement of diastole depended not on the vis a tergo of the
blood, but on the elastic reaction of the heart's walls, by the fact
that, after opening the thorax, pressure is at zero in the cavity of
the right auricle and adjacent vein. This one fact is sufficient
to establish the doctrine of diastolic activity in the mechanical
sense.

But in this connection arises the (juestion of the origin of this
elastic reaction at the commencement of diastole. Is it dependent
on cardiac muscle properly so-called, or on the elastic tissue
implanted in the walls of the heart ? Certain authors subscribe in
virtue of quite independent arguments to the former of these
theories, admitting a possibility of an active lengthening of the
muscular fibres of the myocardium. The first to express this
view was the English physiologist Carpenter, who, at the end of
1855, maintained that the active force which causes the heart to
dilate must originate in the myocardium proper. He propounded
the hypothesis that just as active muscular contraction, which
causes the muscle to shorten, depends on the attraction of the
particles of which that muscle is formed, so the reciprocal re-
pulsion of those same particles must produce the active elongation
of the muscle fibre.

In 1871, not being aware of Carpenter's hypothesis, we brought
forward another, essentially similar to it, but differently expressed.
We suggested that the contraction and subsequent expansion of
the myocardium might be determined by two antagonistic
physiological processes, so that the cardiac diastole would, like
the systole, be an active movement. At a later time this hypo-
thesis was taken up and elaborated by Stefani (infra).

Lastly, mention must be made of Albrecht, who has recently
(1903) published a valuable study on the myocardium. He, too,
considers diastole to be an active physiological process, on the ground
of Verworn's theory of the general physiology of muscle. Accord-
ing to Verworn the expansive phase of the mechanical response
of muscle is active, and is determined by the tendency of the aniso-
tropous substance, saturated during the contractive phase by the

vii MECHANICS OF THE HEAHT 215

katabolic products, to assimilate oxygen and nutrient juices from
the environment. For this purpose the anisotropous substance seeks
to acquire the largest possible superficies, i.e. it expands. Yerworn
does not deny that this expansive movement (i.e. relaxation) is
assisted by numerous extrinsic factors, e.g. the tension of tendons
and fascia, etc., but he still attributes a not inconsiderable function
to the expansive activity proper of the muscle fibres. Albrecht
extended to the heart the idea which Yerworn had formulated for
muscles in general. He accordingly defines diastolic activity as a
functional necessity of recuperation.

Other authors, on the contrary, ascribe the active character of
diastole to the elastic tissue contained in the myocardium. Krehl
appears to have adopted this hypothesis. He holds that there are
many elastic fibres beneath the endocardium, surrouuding the
muscle bundles of the internal layers, which may be thrown into
tension during systole, and react in diastole by dilating the
cavities of the heart. The elastic lamellae which extend from the
semilunar valves passing under the origin of the aorta into the
interior of the muscles may produce the same effect. Lastly, he
believes that the root of the aorta, deeply implanted, and always
distended under high pressure during the energetic systolic
diminution of the base of the heart, must be deformed ; so that at
the commencement of diastole, when it recovers its position of
equilibrium, the pressure must involve .a distension of the soft
muscles. This last idea is a new form of Gaule's hypothesis, as
already refuted. In any case, Krehl's propositions, as a whole,
leave us uncertain whether the dilator reaction of the heart, at
the commencement of diastole, is to be ascribed to the elastic
tissue or to the cardiac muscle. The former is, however, absolutely
put out of court by certain very important facts adduced by
Stefani, which go to determine the physiological character of the
active diastole.

VIII. In a previous paragraph we referred to the changes in
total volume of the heart, during the several periods of its activity.
We said that it diminished during systole, at the termination of
which meiocardia occurs, i.e. the maximal diminution of the heart's
volume ; and that it increases during perisystole until it attains
the maximal volume, or auxocardia, at the commencement of
presystole.

After our first experiments in 1871 (in which, to estimate
the changes in volume of the heart, we employed the pericardial
cavity filled with milk) Franck and Stefani (1877) were the first
who adopted the method of the pericardial fistula for curarised
dogs, kept alive by artificial respiration — tracings of the oscillations
of the total volume of the heart (cardiac plethysmogram) being
recorded on a rotating drum. This is easy enough with simple air
transmission, i.e. by connecting up the cannula applied to the

216

PHYSIOLOGY

CHAP.

pericardium with a tambour and writing lever, artificial respira-
tion being temporarily suspended.

The plethysmograms obtained by this method give an
approximate picture of the quantity of blood with which the

Fio. 69.— Cardiac plethysmograms. (Stefani.) o, b, Descending portion, coinciding with systolic
outflow ; b, c, rapidly ascending portion, coinciding with active diastolic influx ; c, a, nlowly
ascending portion, coinciding with passive diastolic influx ; d, notches, which nearly always
occur on the ascending shoulder.

heart is charged, or which it discharges at the different periods of
its cycle, and consequently of the systolic diminution, and peri-
systolic amplitude of the ventricular cavity.

As appears from the tracings in Fig. 69 we can distinguish : —

(a) A rapidly descending line which coincides with the period
of systolic evacuation.

(ft) A rapidly ascending line (in which there is invariably a
notch) corresponding with the period of active diastole.

(c) A slowly ascending line (sometimes horizontal or even
slightly descending as shown in Fig. 70), which corresponds to the
time of passive diastole and presystole.

It is obvious that neither the period of presystole nor the
succeeding interval of tension or latent systole, during which the
total volume of the heart undergoes no important modification, can
be distinctly shown in cardiac plethysmograms. Since in the

FIG. 70.— Cardiac plethysmograms, in which the line •:, a of passive refill is descending or
almost horizontal.

third period of the plethysmogram there may be a slight augmenta-
tion of cardiac volume, or it may be stationary, or diminish, the
deduction of Stefani seems valid, to the effect that " the venous
current (in consequence particularly of presystole) must in the
first case suffer a simple retardation, in the second an arrest, in

vii MECHANICS OF THE HEART 217

the third a reflux." The most important results which Stefani

obtained from analysis of cardiac plethysmograms are as follows : —

(a) Their magnitude varies considerably not merely in different

animals, but also in the same animal, showing that the heart,

Fie. 71. — A, Plethysmogram obtained under normal renditions ; B, Plethysmogram from same
dog, during dyspnoeie excitation of vagus.

under different circumstances, is able more or less completely to
nil and empty itself of blood, " so that it may assume a volume
considerably greater than that attained in the preceding cycles,
independent of any modification in the frequency of the beat"
(This comes out clearly in Figs. 69, 70, 71.)

(&) There is no perceptible difference in the duration and form
of the two first periods of the plethysniogram (line of systolic

FIG. 72.— Plethysmogram showing augmentation of cardiac volume during excitation
of left vagus.

evacuation and active diastolic refill) with changes in frequency
of the heart's beat. It is only the third period (of slow passive
refilling) that varies in duration and form with the acceleration
or retardation of the cycle. (This is demonstrated in the tracings
of Figs. 71, 72, 73.)

218

PHYSIOLOGY

CHAP.

From this Stefani draws the logical conclusion that both the
first and second periods of the plethysmograrn are the effect of
physiological activity — while only the third can be regarded as the
effect of repose of the heart.

Fi<;. 73.— Pli'thysmogram showing that stimulation of oii»> vagus by strong induction currents
has no e fleet on systolic evacuation, but conspicuously increases the period of passive refill.

(c] If the vagus be excited, either directly or by cessation of
artificial respiration (which has the effect of increasing the venosity
of the blood), profound changes appear in the cardiac -plethys-
inograms, varying in form according to the degree of excitation
and the excitability of the nerve, but all having this in common
that the ascending line of the diastolic refill has a considerable
upward lift, which signifies that the heart acquires a greater
volume. (Tracings of Figs. 71, 72, 73, 74, 75.)

This phenomenon cannot be dependent on the slowing or
suspension of the beats of the heart, because on the one hand the
increase of volume occurs rapidly and in a degree which far exceeds
the normal, and on the other there is a marked demarcation
between that part of the line of refill which corresponds with active
and that which corresponds with passive diastole ; and finally
because the heart is able on excitation of the vagus to attain its
maximum volume before the venous pressure has had time to rise

to any considerable
extent (Fig. 76).

Stefani considers
that these facts con-
firm the doctrine
we have maintained
since 1871, to the

Fio. 74.— Plethysrnogram in which gentle excitation of one vagus effect that the VagUS
(at +) makes systolic evacuation incomplete, while it increases • rlioofrJin narxro

diastolic refill. 1S a OUdSlOllC nerve,

in the sense that

" it actively provokes increase of volume in the heart, by modify-
ing the physiological condition of the cardiac muscles."

This same theory of the mode of action of the vagus upon the
heart (to be discussed in detail in the next chapter) was successively
put forward by Eossbach (1882), Heidenhain (1882), Williams
(1887), Tigerstedt and Johannssohn (1889), and also by Francois-

VII

MECHANICS OF THE HEAET

219

FIG. T5. — Plethysmogram showing that strong ex-
citation of one vagus (at -j-) exaggerates effect
shown in preceding figure.

Franck (1891), who in 1877 had pronounced in precisely the
opposite sense.

It thus became necessary to determine more exactly the nature
of the action of the vagus, in so far as it is a diastolic nerve, capable,
i.e., of modifying the internal
physiological state of the
cardiac muscles. With this
object, Stefani undertook to
measure the pressure that
must be exerted on the outer
surface of the heart in order
to arrest the circulation of
the blood. This he compared
with the pressure simultane-
ously exerted upon its in-
ternal surface, and noted the
changes in the difference between the two pressures, according as
the vagus was excited or paralysed. From this ingenious and
original research Stefani obtained most important results, which
we may summarise in a few words.

A pericardial fistula was made on a dog, the cavity being
connected by a T-shaped tube, on the one hand with a pressure
bottle filled with 1 per cent solution of NaCl, on the other with
a mercury manometer. When the fluid is made to descend into
the cavity of the pericardium, the manometer measures the pressure
exerted on the outside of the heart. Another manometer, in which

an alkaline, anti-coagulant
solution is substituted for
mercury, is connected with
a glass tube introduced in-
to the vena cave superior,
in order to measure the

venous pressure acting
upon the internal surface
of the heart. A third
mercury manometer can
be connected with the
carotid in order to rneas-

Fio. 76. — The upper curve represents the venous pressure, 1 . ,

the lower the plethysmograrn. At «, a (the corre- U1'6 the arterial pressure,
spending points on either curve) one vagus was strongly j T,vr.^nv<- 4nil w:<- U fV,a

excited. The two curves show that the augmentation ^n proportion Wltll bllt

of cardiac volume corresponds to a slight fall of venous increase of "Pericardial
blood pressure.,

pressure, the venous pres-
sure increases owing to the obstruction of the flow to the heart,
while arterial pressure diminishes owing to the diminished out-
put from the heart. When the pericardial pressure is so high
that it completely inhibits the flow of blood to the heart and
circulation is arrested, the arterial pressure rises to 15-20 min. Hg

220

PHYSIOLOGY

CHAP.

and the venous pressure to 12-18 cm. H20. If one vagus is
stimulated by an induction current at the moment at which
circulation ceases, the interesting phenomenon of a rise in ar-
terial pressure may be observed, and cannot be explained other-
wise than by admitting with Stefani that the heart is capable,
under vagus stimulation, of charging itself with blood, even against
the pericardial pressure, which previously impeded this loading.
The vagus is thus able to excite active dilatation of the heart.

Stefani applied the term diastolic pressure to that exerted by
the heart in diastole upon the surrounding fluid of the pericardium,
by which it overcomes the resistance, distends its cavities, and
permits the blood to penetrate it. He measured this diastolic
pressure in eight dogs, determining the difference between the
pressure in the pericardial cavity and in the vena cava. The
results are as follows : —

At the moment of Arrested Circulation.

No. of

Animal.

1

Pressure in Pericardium.

Pressure in Vena Cava.

Diastolic Pressure.

1

35 cm. H

,0

10 cm. H.,0

25 cm. H.,0

2

20 ,,

6

14

j

3

40 „

8

32

4

27 „

13

14

j

r}

27 ,,

8

19

5

6

27 ,,

13

14

,

/

25 „

14

11

)

1 8

26 „

12

14

'

It appears from these figures that in ordinary diastole the
heart develops a pressure upon the pericardial fluid which is capable
on an average of supporting a column of water of 19 cm. This
result harmonises well with that obtained by the minimum
manometer of Goltz and Gaule as described above.

On measuring the pericardial pressure capable of arresting the
circulation, before and comparatively soon after section of the vagi,
Stefani obtained the following results on five dogs :—

.Pericardical Pressure able to Arrest Circulation.

No. of
Animal.

Difference.

Before Section of Vagi.

After Section of Vagi.

1

35 cm. H20

20 cm. HoO

15 cm. H20

2

26 „ „

16 ,, „

10 „ „

3

21 „ „

12 „ „

9 „ „

4

24 „ „

13 „ „

11 p, „

5

23 „ „

13 „ „

10 ,, „

VII

MECHANICS OF THE HEAET

221

Diastolic pressure is accordingly reduced after division of the
vagi to an average of 11 cm. H20, i.e. to a value little more than
half of that developed with intact vagi, which confirms the diastolic
or dilator action of the vagi upon cardiac muscle.

If the vagus is excited after bringing the circulation to a
standstill by pericardial pressure, the manometer in connection
with the pericardial cavity shows a rise of pressure which soon falls
again when stimulation ceases. If these oscillations of the mano-
meter be recorded on a rotating cylinder, the following tracing
(Fig. 77) is obtained, which is a new and direct proof that the
degree of diastolic dilatation is regulated by the vagus.

Lastly, in order better to control the theory of diastolic activity,
Stefani successfully employed certain poisons (atropine, digitaline,
and strychnine), measuring the diastolic pressure before and after
injection of the drug, and before and after section of the vagi.
He came, in a few words, to the following conclusions : that

FIG. 77. — The recording mercury manometer is connected with the pericardial cavity. Show
disappearance of plethysmographic oscillations in the heart, in consequence of hydrostatic
pressure exerted within pericardium. The vagus was stimulated in the neck at + , slightly at
first, afterwards more strongly. — marks close of excitation. During stimulation the heart
dilates, and resumes its original volume at the close of excitation. (Stefani.)

atropine lowers the diastolic pressure because it paralyses the
dilator action of the vagi, and that digitaline and strychnine increase
the diastolic pressure because they act directly upon the cardiac
muscle, and render it capable of active dilatation in excess of the
normal.

Until these important facts determined by Stefani are con-
tradicted or shown to be fallacies, we shall continue to regard the
theory of diastolic activity (which we formulated in 1871) to be
well founded, both from a purely mechanical and from a physio-
logical point of view.

In the ninth chapter we shall discuss certain experimental
data which enable us to determine, up to a certain point, the
nature of the internal process by which the vagus develops and
regulates the activity of the diastole,

IX. After developing the mechanism of the systolic evacuation
and diastolic refill of the heart it is easy to deal with the question
of the cardiac beat or pulse, which, like the heart-sounds, con-
stitutes an important external sign in the investigation of this

222 PHYSIOLOGY CHAP.

organ in man and in intact animals. It consists in a rhythmical
elevation of the intercostal spaces corresponding with the peri-
cardial region to the left of the sternum. The impact is generally
supposed to be greatest at the level of the fifth intercostal space, a
little within the mamillary line, where the apex of the heart lies
normally ; but from a series of careful investigations by Mariannini
and Narnias (1882) it appears, on the contrary, that the point
at which the beat of the heart is normally strongest corresponds
more frequently (in 67 per cent) with the fourth than with the
fifth intercostal space, in the supine horizontal position. It is
usually perceived by palpation, but in thin persons with large
intercostal spaces it is visible to the eye.

Harvey was the first to point out that the cardiac beat
occurred during systole. His theory is the more valuable, inas-
much as he had the opportunity of directly observing the beats of
the heart on Viscount Montgomery, who had lost part . of his
thoracic wall through an accident, so that the exposed heart was
visible (Exercitatio de generatione animalium, lii.).

This generally accepted doctrine, which has received ample
confirmation from modern researches with the graphic method, was
at one time contradicted, on the strength of fallacious observations
in which the ictus cordis was regarded as the effect of the sudden
dilatation of the ventricles at the moment of presystole. Corrigan,
Stokes, Pigeaux, Burdach (1832), Beau (1835), Baccelli (1859),
successively held a brief for this theory, which owed its success, as
Marey remarked, " a ce qu'elle etait simple et logiquement deMuite."

The first promoters of this theory, Corrigan and Stokes, ad-
mitted their error, and that it is still perpetuated by the Italian
clinician Baccelli is doubtless the result of an ambiguity. At the
Kome Congress in 1894 he maintained that the impact of the
heart coincides with the moment immediately preceding systole.
It is obvious that by systole he means the period of evacuation or
ventricular efflux, as was always understood by physiologists as
well as clinicians, prior to the introduction of the graphic method.
But since it is now well established that the efflux is preceded by
a period of tension or of latent systole, which lasts from 0*10 to 0*08",
it is clear that this must be the moment with which, according to
Baccelli, the impact of the heart coincides. We are completely at
one with this opinion, provided it be understood in the sense that
the displacement of the thoracic wall reaches its greatest height
during that period. It agrees, in fact, perfectly with what we
learn from the cardiogram.

The method now generally adopted by physiologist*) and clinicians in
recording the tracings of the cardiac beat (cardiogram) is that of tambours
with an elastic membrane and air transmission. Hiirthle, in 1892, made an
interesting control research with the different models of cardiographs as
employed by various workers. This was the more useful since we should,

vii MECHANICS OF THE HEART 223

a priori, expect a certain number of tlie various characteristics found by
different authors in the cardiograms of healthy individuals, to be due to the
method or rather to the instruments employed. Hiirthle performed a double
series of experiments. In the first place, with the tambours of Marey, Knoll,
and Grunmach, lie recorded an identical impulse, mechanically produced.
Then with the same tambours lie successively recorded the cardiograms of one
healthy individual. The result of his experiments showed that while Marey's
tambour was not wholly free from error it recorded the impulses in such a
way as to reproduce their characteristics accurately. The cardiographs
invented by Knoll and Gnmmach, on the other hand, were very fallacious.

The following tracing (Fig. 78), obtained by Frangois-Franck
from a woman suffering from ectopia cordis congenita, is convincing
since in this case the heart, having dropped down through an
abnormal opening in the diaphragm, beat beneath the skin in the
linea alba of the epigastrium. It is clear that the rhythmical
elevation determined by the ventricular systole commences exactly
at the close of presystole.

FIG. 78. — o.d, Cardiograms of right auricle ; r.d, cardiograms of right ventricle, recorded
simultaneously by two separate explorers with writing levers. (Francois- Franck.)

No less convincing are the cardiograms obtained from man
under normal topographical conditions of the heart, which are
recorded simultaneously by an electric signal at the precise
moment at which the first and second sounds are first heard. We
have shown that the first sound is concomitant with systole, and
any one who questions whether it begins at the moment of
tension, i.e. prior to the ventricular efflux, need only study the
tracing obtained by Marey from the horse with a cardiographic
sound introduced into the right ventricle (Fig. 79).

Starting from this well-established fact, the cardiograms of
the heart -beat (Fig. 80) which Edgren obtained from his
cardiograph, used simultaneously with the stethoscope, have
the same value and lead to the same conclusions as the fore-
going tracings of Francois- Franck.

Since the cardiac pulse is proved to be initiated in the rapidly
ascending movement before the intraventricular tension has suc-
ceeded in opening the semilunar valves, all those hypotheses are
necessarily discredited which seek to explain this phenomenon.

224

PHYSIOLOGY

CHAP.

as the effect of the systolic outflow of the blood into the
arteries.

Carlile (1833) and Ludwig (1848), in order to explain the
cardiac pulse, took into special consideration the conical form
assumed by the ventricular mass in systole, and the forward

Fio. 79. — Oscillations of pressure in right ventricle (V. D.) of horse, transmitted through cardiac
sound to recording tympanum. (Marey.) The times at which the first and second heart-sounds
begin to be heard are simultaneously recorded by an electric signal.

inclination observed in the base of the ventricle, which causes the
apex of the heart to impinge on the wall of the thorax. But
since this change of form and movement of the heart is the effect
of systolic evacuation, it is obvious that it cannot be adduced to
explain the sudden rise seen in the cardiograms during the period
of tension, i.e. before the blood begins to stream out of the
ventricles.

In a recent work Keith (1904) has taken up the idea of Ludwig,
developing it by subtle anatomical arguments and with ingenious
experimental methods for which we refer the reader to the
original memoir. Keith maintains that the base of the ventricle

FIG. 80. — Cardiogram transmitted to cardiograph from fifth left intercostal space in man. (Edgren.)
The times at which the first and second heart-sounds begin to be heard are simultaneously
recorded by an electric signal.

rises slightly during presystole. This displacement depends more
particularly on the peculiar disposition of the pectinate muscles.
In consequence of this rise of the base of the ventricle, it almost
meets the blood which is driven towards it. When, on the
contrary, systole sets in, upon which the ventricle is restrained in
every dimension, its base is pushed out in the opposite direction.

VII

MECHANICS OF THE HEART

225

It follows that the apex of the heart does not approach the base,
but on the contrary the base approaches the apex, so that the
latter is energetically thrust against the thoracic wall and produces
the cardiac beat. It may, however, be objected to this ingenious
experiment that the sharp lift produced by the cardiac impulse
takes place not during the period of efflux, but in that of
tension.

The same reason invalidates the doctrine of the recoil (recul
balastique) supported particularly by Skoda (1842) and Htffelsheim
(1854), which in so far as it assumes locomotion of the heart
resembles the preceding. It is also contrary to the fact that the
cardiac pulse is not confined to the region of the apex in the fifth
intercostal space, but (as we have seen) is even more frequently
accentuated in the fourth intercostal space.

FIG. 81.— The upper tracing is an artificial cardiogram, obtained from a perfected model. The
lower tracing is a cardiogram taken on man. In both tracings the rise O represents the effect
of presystole ; the rise V, the effect of systole. (Marey.)

Still more inadequate is the theory maintained by Senac
(1749), Bahr (1862) and others, which derives the cardiac pulse
from the downward impulse of the apex in consequence of the
distension of the arterial arches (aortic and pulmonary) determined
by the pressure produced in these by each wave of blood that
surges from the heart. We have seen that the apex is the least
mobile point of the heart in the longitudinal direction, because the
elongation of the arterial arches almost exactly compensates for
the systolic shortening.

All these mechanical factors intervene as accessory and com-
plementary data in the production of the ictus, during the period
of systolic evacuation ; but the essential and fundamental cause of
the phenomenon is the tension and hardening of the heart during
the whole period of systole. The heart is in perpetual contact with
the internal wall of the thorax and the external parts of the lungs,

VOL. I Q

226 PHYSIOLOGY CHAP.

which cover it to a great extent ; but during the period of passive
diastole or repose, its walls are soft and easily compressible, while
in the systolic period they become hard and tense, and this is',
enough to determine the phenomenon of ictus. This theory,
adumbrated by Harvey, was clearly set forth by Kiwisch (1846),
and upheld more recently by Baniberger, and by Chauveau and
Faivre (1856) ; but Marey (1863-76) was the first to give convincing
proof of its accuracy by his ingenious schemata of the movements
of the heart. He succeeded with these in producing artificial
cardiograms, which exhibit all the most important features of the
cardiograms obtained on man, as shown in the two tracings of
Fig. 81.

The analytical study of these features is of great scientific and
practical interest, but we must consider them together with the
waves exhibited by the arterial pulse and the sphygmograms, with
which they are intimately connected by their origin.

X. The systolic movements of the heart in the period of tension
must, since they determine a sudden elevation of the intercostal
spaces of the precordial region, produce a rhythmical dilatation of
the thoracic cavity, in proportion with the energy and rapidity of
the impact. Further, the diminution of the total volume of the
heart during the period of systolic efflux until it reaches meiocardia
is commensurate with the quantity of blood expelled from the
arteries. Half this blood, passing through the pulmonary system,
does not leave the thoracic cavity ; but the other half, passing
through the aortic system, issues rapidly from the thorax, pro-
ducing a comparative vacuum, which cannot be compensated by
the blood that simultaneously enters the thorax by the venae
cavae. During systole, therefore, the thoracic cavity must, in
virtue of distinct mechanical conditions which succeed each other,
develop an aspiration, capable of being felt in the intercostal
spaces not in contact with the heart — in the lungs, the diaphragm
and the veins adjacent to the thorax.

In thin persons it is, in fact, easy to see coincidently with
systole, a depression of the intercostal spaces, to which the name of
negative cardiac pulse has been given (to distinguish it from the
positive pulse that can be observed in the region of the apex of
the heart and its vicinity). At the same moment there is also a
negative pulmonary pulse, i.e. a gentle inspiratory movement of
the lungs which, when the glottis is open, may produce a systolic
diminution in the pressure of the air contained in the buccal cavity
or nasal fossae. It is also possible to detect a negative pulse of
the abdominal wall in the epigastric region, which is the effect of
an aspiration exerted by the thoracic cavity on the diaphragm.
Lastly, it is possible also to observe a negative systolic pulse in the
jugular veins due to the same cause, although here it is probable
that other mechanical factors co-operate, which are independent of

VII

MECHANICS OF THE HEAET

227

the changes of intrathoracic pressure, and depend on variations
of pressure within the right auricle.

Many physiologists have exercised their critical and technical
abilities upon these phenomena of negative pulsation, the indirect
effects of the positive cardiac pulse and of nieiocardia. Buisson
(1861) was the first to describe the negative thoracic pulse, and
the negative pulmonary pulse ; Voit (1805) again observed the

Co

FIG. 82. — Ara, Pneumograiu taken from the nostrils ; C'a, sphygmogram from the cuiotids, recorded
simultaneously with open glottis. (Mosso.) ;. It will be seen thatlthe inspiratory movement
precedes the carotid pulse.

rhythmical systolic inspirations, and held them to be the effect of
the diminution in the heart's volume ; Ceradini (1869) clearly
perceived the mechanical consequences of nieiocardia and auxo-
cardia, but made no experimental study of them ; Paul Bert
(1870), among the oscillations of air-pressure within the trachea of
a dog, included those dependent on cardiac movements ; Loven
(1870) took tracings of the negative thoracic, and the positive pulse
of the radial artery, and observed them to be simultaneous ; Landois
(1876) obtained tracings of the cardiac oscillations of air-pressure
of the nasal cavities (which he termed cardio-pneumatic curves),

FIG. 83. — Co, Cardiogram taken on man at fifth intercostal space ; Na, pneumogram taken from
nostrils. Simultaneously recorded with open glottis. (Mosso.)

and was the first to distinguish the negative pulse which can be
verified at each systole when the glottis is open, from the positive
pulse which occurs when the glottis is closed, and the nasal
cavities function as a space distinct from those of the pulmonary
passages, in which there is diminished pressure with each wave of
blood that inundates the arterial vessels.

Mosso (1878) was, however, the first who grasped this subject
fully, and employed an exact experimental technique. In his cardio-
pneumatic curves obtained with an ordinary Marey's tambour

228

PHYSIOLOGY

CHAP

connected with the nasal cavities, he was able to distinguish a first
inspiratory depression, due to the systolic lift of the intercostal
spaces of the precordial region, from a second, later depression due
to meiocardia. This is plain in the two tracings (Figs. 82 and 83),
in the first of which the negative pneumograin of the nasal fossae
is recorded simultaneously with the sphygmogram of the carotid,

FIG. 84. — jV«, Positive pneumogram taken from nostrils with •efteft- glottis ; Co, carotid
sphygmogram, recorded simultaneously. (Mosso.)

and in the second with the thoracic cardiogram. Repeating the
experiment with closed glottis, the negative pneumogram is trans-
formed into the positive (as shown on Fig. 84). All who, like the
author, are incapable of holding their breath without closing the
glottis, obtain, on the repetition of Mosso's experiment, positive
pneumograms only. This was the case (as Mosso points out) with
Terne van der Heul (1867), who, on making these experiments
under the guidance of Bonders, invariably obtained results that
contradicted the above theory.

If a sound is introduced into the oesophagus, covered at the

FIG. 85.— I, Cardiac sphygmogram from dog, transmitted from oesophageal iexplorer to recording
tambour during long expiratory pause; II, effects of cardiac beats transmitted from rectal
explorer, recorded simultaneously. (Luciani.)

end by a very fine rubber membrane like the finger of a glove,
the canal is transformed into an intrathoracic cavity communi-
cating with the exterior in such a way that (on connecting up
the external opening of the sound with a tambour and
writing lever) the vibrations produced within the thorax can
all be traced on the rotating cylinder. The negative oscilla-
tions are recorded by descending, the positive by ascending
lines. We were the first, in 1877, to introduce this method into

VII

MECHANICS OF THE HEART

229

physiological technique, and to recognise in the tracings, not
merely the large oscillations dependent on the respiratory move-
ments, but also the lesser variations due to the movements of
the heart.

We found the cardiac sphygmogranis obtained by the oeso-
phageal method to be of very complex form, varying greatly,

FIG. 86. — From same dog as preceding figure, after section of cervical cord between fifth and .sixth
vertebrae. (Luciani.) It will be seen that diaphragmatic respiration alone persists. I, In-
spirations ; E, expirations. The cardiac sphygmogranis are reduced to minute oscillations,
and are only visible on the oesophageal tracing.

particularly in their dimensions, with the condition of the
animal (Figs. 85 and 86). We also found that they could not be
dependent exclusively on the effects of meiocardia and auxocardia,
but were influenced also by the nature of the relations of contact
between the heart and the oesophagus, since on opening the
thoracic cavity they do not entirely disappear, but are considerably
modified (Fig. 87).

Leon Fredericq (1888) took up this point again in order to
make a more detailed analysis of the oesophageal sphygmogranis,
and obtained complex forms of oscillations which closely resembled
the very interesting oscillations which he observed in the cavity of

FIG. 87.— Cardiac sphygmograms transmitted from oesophageal explorer during apnoea of forced
artificial respiration in anaesthetised dog. (Luciani.) C, With closed thorax ; A, with opened
thorax ; C', A', the same on another anaesthetised dog ; C", A", the same on a third cnrarised
dog.

the auricles (see Fig. 68, p. 207). From this he concluded that
they were dependent on a direct transmission to the oesophagus of
the active and passive movements of the left auricle, pointing out
the intricate anatomical relations between these two organs. He
denied that they were in any way dependent on the effects of
meiocardia or auxocardia, because they are not abolished by the
opening of the thorax. This last conclusion, however, does not
take into account the fact, which we discovered twelve years

230 PHYSIOLOGY CHAP.

earlier, that the pulsations in the oesophagus are considerably
changed and simplified after opening of the thorax.

Martius (1888), on the other hand, while almost contemporary
with Fredericq, considered only the effects of meiocardia and auxo-
cardia in interpreting the oesophageal pulsations, and thus came
to a one-sided conclusion in the opposite direction.

XL Before leaving this interesting subject of cardiac
mechanism, it is necessary to form some approximate conception of
the work that is usually performed by the heart in a unit of time.

The work of the heart is equal in the time unit to the weight
of the blood it is capable of moving, multiplied by the height of
the pressure to which the said weight is lifted. To determine this
work it is necessary to form a proper appreciation on the one
hand of the mechanical value of each cardiac revolution, i.e. of the
quantity of blood that passes from veins to arteries in the said
unit of time ; on the other, of the height of pressure in the arteries
nearest to the heart.

The weight of blood driven into the arteries at each systole
depends both on the degree of diastolic filling (auxocardia), and on
the degree of systolic evacuation (meiocardia). It is very difficult
to arrive at an exact determination of this weight, since it varies
with varying conditions. The values of 185*5 and of 180 grins,
cited by Volkmann and Yierordt in calculating the work of the
heart are certainly exaggerated. The values adopted by Fick
(50-75 grms.), by Tigerstedt (50 grins.), and by Zuntz (60 grms.)
are probably nearest to the truth.

On the other hand, the mean pressure of the aorta may be taken
as approximately equal to 150 mm. Hg, i.e. in round figures to a
column of blood 2 metres high, and the pressure in the pulmonary
artery may be taken as about a third of the aortic pressure.

Assuming that the left ventricle drives some 60 grms. of blood
into the aorta at each systole under a pressure of 2 in. of blood, and,
allowing for the velocity acquired by the same, which is a negligible
quantity, we obtain a yield of 120 grammetres at every revolution.
, Given 72 revolutions per minute, it is easy to calculate that the
work done by the left ventricle in 24 hours represents about
12,450 kilograrnmetres. If a third of this, -i.e. 4150 kilogram-
metres, be added as the approximate work of the right ventricle,
the total work of the heart in 24 hours may be reckoned as
16,600 kilograrnmetres.

The friction to which the blood is submitted in its passage
through the closed vascular system transforms the entire work of
the heart into heat. Starting from the fact that 425 kilogram-
metres are necessary for the development of 1 calorie, the 16,600
kilogrammetres of the heart's daily work represent some 39 calories,
corresponding with the heat developed by the combustion of less
than 5 grms. of carbon.

vii MECHANICS OF THE HEART 231

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O. KURSCHNER. Herzthtitigkeit. Wagner's Handwbrterbuch der Physiol., Zweiter

Band, S. 30-107. Braunschweig, 1844.
O. LUDWIG. Lehrbuch der Physiologie des Menschen. Zweite Auflage, Zweiter

Band. Leipzig und Heidelberg, 1861.

R. TIGERSTEDT. Lehrbuch der Physiologie des Kreislaufes. Leipzig, 1863.
CHAUVEAU e ARLOING. Coeur (Pliysiologie), Dictionnaire encycloped. des sciences

medicales, tome xviii. pp. 314-382. Paris, 1876.
MAREY. La Circulation du sang a 1'etat physiologique et dans les maladies. Paris,

1881.
L. LUCIANI. Deir attivita della diastole cardiaca. Rivista clinica. Bologna, 1871,

1874, 1876.
A. STEFANI. Cardiovolume, pressione pericardicae attivita della diastole. Memoria

letta all' Accademia medico -chirurgica di Ferrara il 5 agosto 1891.
O. CERADINI. II Meccanismo delle valvole semilunari del cuore. Gazzetta medica

italiana-lombarda. Milano, 1871.
O. PALADINO. Contribuzione all' anatomia, istologia e iisiologia del cuore. Movi-

mento medico-shirurgico. Napoli, 1876.
L. LUCIANI. Delle oscillazioni della pressione intratoracica e intraddominale.

Archivio di Bizzozero, anno II. Torino, 1877.

A. Mosso. Sul polso negativo. Archivio di Bizzozero, anno II. Torino, 1878.
L. FREDERICQ. La Pulsation du coeur chez le chien. Travaux du laboratoire,

tome ii. 1887-88. — Arch, internationales de physiol., vol. v. 1907.
J. G. EDGREN. Cardiographische und sphygmographische Studien. Skandina-

visches Archiv fur Physiologie, Erster Band, S. 66-151. Leipzig, 1889.
L. KREHL. Beitrage zur Kenntnis der Fiillung und Entleerung des Herzens. Aus

dem physiologischen Institut zu Leipzig, xvii. Band der Abhandhmgen der

K. Sachs. Gesell. d. Wissenschaften. Leipzig, 1891.
TK;ERSTEDT. Intrakardialer Druck und Herzstoss. Ergebnisse der Physiologie,

1902. (60 works are cited in this article.)
E. EBSTEIX. Die Diastole des Herzens. Ergebnisse der Physiologie, 1906. (187

works are cited in this article. )

Recent English Literature.
AV. P. LOMBARD and W. B. PILLSBUIIY. Secondary Rhythms of the Normal Human

Heart. Amer. Journ. of Physiol., 1900, iii. 201.
R. CUSHNY. On Periodic Variatic

A. R. CUSHNY. On Periodic Variations in the Contractions of the Mammalian

Heart. Journ. of Physiol., 1899-1900, xxv. 49*.
J. A. MACWILLIAM. Rigor Mortis in the Heart and the State of the Cardiac Cavities

after Death. Journ. of Physiol., 1901-2, xxvii. 336.
D. J. LINGLE. Restorers of the Cardiac Rhythm. Amer. Journ. of Physiol.,

1905, xiv. 433.
Y. HENDERSON. The Volume Curve of the Ventricles of the Mammalian Heart, and

the Significance of this Curve in Respect to the Mechanics of the Heart-Beat

and the filling of the Ventricles. Amer. Journ. of Physiol., 1906, xvi. 325.
T. LEWIS and A. S. MACNALTY. A Note on the Simultaneous Occurrence of Sinus

and Ventricular Rhythm in Man. Journ. of Physiol., 1908, xxxvii. 445.

CHAPTEK VIII

THE BLOOD-STKEAM : MOVEMENT IN THE VESSELS

SUMMARY. — 1. .Fundamental laws of hydrodynamics for passage of fluid through
rigid tubes. 2. Application of these laws to haemodynaiuics. 3. Mechanical
effects of elasticity of vessel walls and intermittence of flow of blood from heart ;
laws of wave motion. 4. Method of measuring and automatically registering
variations in blood pressure. 5. Principal results obtained. 6. Methods of measur-
ing velocity of circulation ; experimental results. 7. Sphygmography and sphygmo-
grams representing pulsatory oscillations in pressure. 8. Comparison of cardiograms
and sphygmograms registered simultaneously, indicating duration of principal
phases of cardiac cycle in man. 9, Comparison of several sphygmograms registered
simultaneously from arteries at different distances from the heart, indicating rate
of transmission of primary and of dicrotic wave. 10. Tachymetry and tachygrams
representing pulsatory variations in current velocity. II. Plethysmography and
plethysmograms representing pulsatory oscillations in the volume of the arteries.
12. Schema of mechanical conditions of the circulation in the three great vascular
systems ; determination of duration of the entire circulation. Bibliography.

WHEN the circulation is observed under the microscope (see Chap.
VI., 8) it is easy to detect a phenomenon which is among the
most fundamental in Haemodynamics : the movement of blood in
the vessels is continuous ; continuous and rhythmically accelerated
in the arteries, continuous and constant in the veins. The analysis
of this complex phenomenon in its details and in its elements, the
determination of the mechanical conditions on which it depends,
and the laws by which it is governed, form the contents of this
chapter.

I. The movement of the blood from the heart through the
vessels is regulated and determined, like the movement of water
driven rhythmically through a tube from a pump, by two
antagonistic influences : the energy developed from the heart, or
pump, which drives the fluid through the vessels; and the
resistance represented by the internal walls of the vessels, owing
to the adhesion of the fluid, and its viscosity. The velocity of each
molecule of fluid is proportional to the difference between the
impulses felt by each a tergo and a f route. The more the driving
force overcomes the sum of the resistances, the faster will be the
flow of a fluid through the system. In order, however, to
form a more exact and concrete idea of the mechanism of the
movement of fluids, it will be well to review certain principles

232

CH. viii BLOOD-STEEAM : MOVEMENT IN VESSELS 233

of hydrodynamics, which are intimately connected with haemo-
dynamics.

(a) Let us take the simplest case of a fluid contained in a vessel
having an outlet in its base. As soon as this is opened, the
resistance offered to the hydrostatic pressure over the outlet
vanishes, and the fluid pours out through the opening. Accord-
ing to Torricelli's theorem (1643), the velocity (v) with which a fluid
escapes is (apart from the resistance it encounters) exactly equal
to that which a body would acquire in falling free through the
height of the column of fluid to the orifice. It is therefore in-
dependent of the nature of the fluid, and depends on the pressure,
i.e. on the height (H) of the column of fluid, and is proportional
to the square root of this height, i.e. it increases as 1, 2, or 3, when
the increment of height is as 1, 4, 9. If the acceleration due to
gravity at each second (which = 9'8 in.) is represented as g, we
have : —

(5) When a rigid horizontal tube is joined to the orifice of the
same vessel (in which a column of fluid is maintained at equal
height and constant diameter throughout its length) the velocity
of outflow, and therefore the amount of fluid escaping from the
end of that tube, will be less than in the previous case, because a
portion of the available hydrostatic pressure will be applied to
overcoming the new resistance which the fluid encounters in its
passage through the tube, and cannot therefore add to the velocity
of the escaping fluid.

The resistances are represented by the internal friction between
the molecules of fluid, which are forced, partly by the adhesion of
the external layer of fluid to the walls of the tube, partly by
viscosity (see p. 151), to glide one over the other. As we have seen
elsewhere (p. 189) the velocity of the single-current threads, into
which we may consider the cylinder of fluid driven through the
tube to be broken up, increases from the periphery to the axis of
the cylinder, where it is maximal. The mean velocity corresponds
with half the maximal velocity observed in the axis.

Since liquids are incompressible, i.e. can neither be compressed
nor the reverse in their passage through tubes, it follows that
their average velocity must be equal at every section of the same,
also that the amount passing every section in the unit of time
must be equal.

Owing to internal friction the fluid exerts a lateral pressure on
the walls of the tube, which can be measured by fixing manometer
tubes, or piezometers, perpendicular to the axis (Fig. 88). The
height to which the fluid ascends in the piezometers decreases
regularly from that in the tube nearest the orifice by which it
enters to that nearest the outflow, so that the highest points of

234

PHYSIOLOGY

OHAV.

the columns of fluid in all the piezometers can be joined by a
straight line. This straight line, which represents the gradual
fall of lateral pressure along the tube, is more or less steep in
proportion to the velocity of outflow.

As shown in the diagram, the total force represented by the
height H of the column of fluid contained in the vessel falls into
two parts : that employed in overcoming the resistance offered to
the free passage of the fluid through the tube /«-', and that employed
in driving the fluid through the tube h. The first is termed lateral
pressure or resistance-head, the second velocity-head.

(c) When the tube connected with the vessel varies in diameter

FIG. 8S. — Schema to demonstrate the laws which regulate the flow of a liquid, at constant pressure,
through a conducting tube with rigid walls and uniform diameter.

in its different parts, the same fundamental law applies as has been
laid down for tubes of constant bore. Since fluid is incompres-
sible, an equal amount must flow through every section of the tube,
independent of its diameter in the time-unit.

In consequence of this law, the velocity of the current in
sections of tubes that vary in diameter stands in inverse pro-
portion to the sectional area.

Since the resistance in the wider parts of the tube is less than
in the narrower sections, it follows that the fluid requires less force
to propel it through the former than it does to pass through the
latter. The lateral pressure accordingly sinks more slowly in the
former and more rapidly in the latter, as shown in Fig. 89. At
points where a wider section of the tube passes into a narrower,
velocity rises, and there is considerable diminution of pressure,
owing to the greater resistance which the fluid encounters ; where,
on the contrary, a wider section follows a narrower, velocity falls,
while pressure on the contrary increases or remains unchanged, or

vin BLOOD-STKEAM : MOVEMENT IN VESSELS 235

falls. This paradoxical fact was explained by Donders as the
result of the formation of vortices, at the base of the dilatation
already referred to (Chap. VII. p. 190). It is certain that the
vortices consume a certain amount of force. When this con-
sumption is considerable, pressure falls ; when, on the other hand,
it is inconsiderable, pressure either remains unaltered, or increases,
as must always occur in consequence of the diminution of velocity.
It is obvious that where the dilatations and constrictions of the
tube occur gradually instead of suddenly, the alterations of velocity
and pressure in its different sections must obey the same laws, with
the simple difference that they are produced slowly, so that their

Fi<:. 89. — Schema similar to that of preceding figure. The rigid conducting tube of equal diameter
is here replaced by a tube of unequal diameter in its various parts. (Rollett.)

course is represented by a curved rather than by a straight gradient,
as in the preceding case.

(d) When the tube connected with the vessel branches into two
or more smaller tubes so that the bed of the current is widened,
i.e. the sum of the sectional area of the branches presents a
larger diameter than the original tube, the result is complicated.
Since the sectional area of the current is enlarged, the sum of the
resistances should be diminished ; on the other hand, the branching
of the tube must introduce new resistances, which increase with
the size of the angle made by the branches. These two opposite
conditions are to a certain extent compensatory. Jacobson's
experiments (1860), however, show that the preponderating in-
fluence is always the widening of the bed, by which the amount of
fluid passing through each cross-section of the system in the
time-unit is increased.

(e) If the tube after branching so as to widen the bed of the

236 PHYSIOLOGY CHAP.

current, unites again into a single outflow tube in which the
sectional area is once more reduced, we obtain a system of canals
which schematically represents the circulatory system. Under
these complex conditions the same fundamental laws hold good
that we have been discussing for the preceding simple cases.

The rate of flow to the different parts of the system is inversely
proportional to the sum of the cross-sections, i.e. to the width of
the current bed. Since the same amount of fluid enters the
system by the inflow tube, and leaves the system by the outflow
tube, in the time-unit, so the same amount of fluid must pass
through every section of the system in the same time, with a
correspondingly greater velocity where the sectional area is
narrower, with less velocity where it is wider.

The pressure at every point of the system must be proportional
to the sum of the resistances which the fluid has to overcome
before reaching the outflow. Since the section of each tube
decreases as the system branches, while the total sectional area
increases, so the sum of the resistances must increase with the
former and decrease with the latter. Which of these two condi-
tions has the preponderating influence ? Experience shows that
when the branching of the system goes as far as the production of
capillary tubes, the sum of the resistances increases in these to
such an extent that it cannot be compensated by the widening,
however great, of the bed of the stream. In a system of capillary
vessels the velocity of outflow is, according to Foiseuille, propor-
tional, not, as in tubes of larger diameter, to the square, but to the
fourth power of the radius.

II. All these laws, in so far as they concern pressure, velocity,
and outflow, are perfectly applicable to the vascular blood system,
since this consists of canals which ramify until they are reduced
into a capillary network with a vast extension of the bed of the
current, and then gradually form into canals again, each of which
has individually a wider cross-section, but which as a whole make
up a narrower channel. Setting aside for the moment the differ-
ences between the circulatory system and the system of conducting
tubes which we have just been considering, it is possible to formu-
late three general laws which are at the base of the circulatory
phenomena.

(a) Laws of Current. — Under normal circulatory conditions,
the amount of blood that flows out of the heart through the arteries
in the time-unit is exactly equal to that which flows into the
heart by the veins ; the amount of blood which enters or leaves
the right or left heart is exactly equal to that which leaves or
enters the left or right heart ; in more general terms, the amount
of blood which passes through any total cross-section of the circu-
latory system is exactly equal to that which passes in the same
time through any other total cross-section of the same system.

vin BLOOD-STKEAM : MOVEMENT IN VESSELS 237

The validity of this law would be absolute if the blood, which — like
all fluids — is incompressible, were circulating in a system of rigid
tubes. But since the walls of the vessels are extensible and elastic,
it is evident that there may be a temporary infraction of it without
disturbing the fundamental conditions of the circulation. The
mass of blood driven through the pulmonary arteries, e.g., may for a
few seconds be greater than that which simultaneously enters the
left auricle through the four pulmonary veins : this must produce
•a certain degree of pulmonary congestion, compatible with life.
If, however, this condition be maintained too long, and if the
converse phenomenon does not immediately succeed it, so that
normal circulatory conditions are restored, the congestion in the
pulmonary vessels will obviously increase to such an extent in a
short time that it presents an invincible obstacle to the now of
blood. Obviously, therefore, the above law has only a relative
value, when the time-unit is taken as an interval of a few seconds ;
it has an absolute value where a longer period, i.e. of one or more
minutes, is taken.

(&) Law of Velocity. — It follows as the necessary result of the
law of outflow that the velocity is inversely proportional to the
cross-section, in the different parts of the vascular system. In
order to determine the proportion in which velocity alters in the
different parts of the circulatory system it is enough to measure
the total sectional area of the vessels in- that part. This is only
possible with the large arteries and veins nearest the heart, which
is the centre of the system ; it is necessary, however, to measure
them not on the dead body, but on the living subject, under the
most normal circulatory conditions possible, so as to obtain the
sectional area under physiological tension and filling of the vessels.
Since the total sectional area or current bed increases slowly on the
one hand, from the large to the small arteries, and rapidly from
these to the capillaries ; and on the other hand, falls rapidly from the
capillaries to the small veins, and slowly from these to the large
veins, it may be stated in general terms that velocity alters in the
inverse sense and same proportion. Since, further, the sectional
area of the aorta is less than the sum of the sectional area of the
two venae cavae, while, on the other hand, the sectional area of the
pulmonary artery is larger than the sum of the sectional area of
the four pulmonary veins, the velocity of the blood-stream in the
systemic circulation will be maximal in the aorta, minimal in the
aortic capillaries, medium in the venae cavae; while in the
pulmonary system it will be maximal in the pulmonary veins,
minimal in the capillaries, medium- in the arteries.

The difference in mean velocity of the flow in the vessels of the
pulmonary and aortic circulations can also be arrived at a priori,
starting from the fact that the capacity of the first system is to
that of the second as 2 : 11. It follows that the pulmonary circula-

328 PHYSIOLOGY CHAP.

tion is completed at a mean velocity some five times greater than
that of the aortic circulation (Jolyet, 1880).

(c) Law of Pressure. — Seeing that pressure in the individual
parts of the system is determined by the sum of the resistances
which the blood has to overcome in order to reach the centre of the
circulation, i.e. the heart, it follows that it must diminish progres-
sively in both the aortic and the pulmonary circulations, from
arteries to capillaries, and from these to the veins, in which last, as
we have seen, it falls to zero. Since the sum of the resistances,
caeteris paribus, derives mainly from the friction surface, and this
increases slowly from large to small arteries, rapidly from the latter
to the capillaries, and then diminishes again slowly from capillaries
to veins, it follows that pressure must fall slowly in the arteries,
rapidly in the capillaries, and then slowly again in the veins.

Broadly speaking, it may be assumed that the sum of the
resistances which the blood expelled from the right heart has to
overcome in order to pass through the pulmonary system, in com-
parison with that overcome by the left heart in traversing the
systemic system, is approximately proportional to the difference in
capacity of the two systems, so that the mean pressure in the
pulmonary circulation must be correspondingly less than that of
the aortic. The dissimilar thickness of wall in the two ventricles
is, as we have seen, an indicator of dissimilar work or force expended
by the two systems.

III. The circulatory system differs from the artificial system of
rigid tubes in two important particulars — the complete elasticity
of its walls and the intermittent character of the impulse, and
therefore of the output of blood from the heart.

If the driving force exerted on the blood by the heart were
continuous and uniform, the elasticity of the system would have no
effect other than to produce a greater or less degree of vascular
dilatation, in proportion with the force of the prevailing pressure ;
but the blood-flow would remain stationary in every part, and be
governed by the same laws as in the system of rigid tubes. If in
the latter the driving force is not continuous but intermittent, the
current through the tubes and the outflow at the end of the system
are also intermittent. But when the impulsive force works inter-
mittently in a system of elastic tubes, then, during the impulse, a
portion only of that force will be employed in propelling the fluid
along the tubes ; while the other portion, by which the tubes are
dilated, will be stored up in the form of elastic tension, and given
back by the reaction at the close of the impulse. Owing
to this elasticity, the current which is intermittent at the
head of the system becomes remittent during its course, till at the
outflow or extremity of the system it is continuous and uniform.

Marey's experimental schema is the best way of demonstrating
the effect of the elasticity of the vessel walls in regulating the

vin BLOOD-STKEAM : MOVEMENT IN VESSELS 239

blood -tiow and making it continuous. A large Mariotte flask
raised to a certain height by a wooden block is employed, having
an orifice at its base opening into a flexible lead tube, divided into
two branches. One of these is attached by a short rubber junction
to a long narrow glass tube, somewhat pointed at the end ; the other
branch is continued as a fine tube of elastic rubber of the same
diameter as the glass tube, ending in a short glass mouthpiece
with the same aperture of outflow as the other (Fig. 90). When
•the tap is opened and the water contained in the Mariotte flask is
allowed to flow out through the two tubes, one having rigid, the
other elastic walls, the amount of fluid escaping simultaneously

FIG. 90. — Mosso's apparatus for demonstrating the effect of an intermittent flow on two tubes,
one having rigid, the other elastic, walls.

from the two tubes will be equal, since the two orifices are equal in
diameter. This proves that when hydrostatic pressure is continuous
and uniform, elastic tubes act like rigid tubes. But if the action
of hydrostatic pressure is rendered intermittent by rhythmically
opening and closing the compression lever carried by the apparatus,
as shown in the figure, it will be seen that the glass tube expels
the water intermittently from its mouth, while the elastic tube
yields a continuous and regular flow. Uniformity of current is
thus shown to be due to the elasticity of the tube.

The impulse imparted to the blood by the elastic reaction of the
vessels is not a new force added to that developed by the heart
during its systolic output ; it is only the restitution of that part of
the impulsive force of the heart which was applied to throwing the
arteries into elastic tension (Berard). Yet even if the elasticity of
the arteries adds nothing to the sum of the driving force of the
heart, it still diminishes the sum of the resistance opposed to the .

240 PHYSIOLOGY CHAP.

entrance of the blood into the arteries. In this way a portion of
the mechanical work of the heart, which would otherwise be lost
in overcoming the great resistance which the blood would meet in
making its way into the arteries, if these were rigid tubes, is saved
and utilised. By the same experimental schema Marey was easily
able to demonstrate that the amount of fluid passing through an
elastic tube is considerably greater than that flowing in the same
time through a rigid pipe, when fluid is driven through both
intermittently.

Another invariable result of the intermittent character of the
driving force exerted by the heart on the arterial blood is the
production of a positive wave at each systole, i.e. a dilatation which
is rapidly propagated in a diminishing degree from the larger to
the smaller arteries, and usually dies out at the threshold of the
capillary network. This positive wave gives rise to the arterial
pulse, and is accordingly known as the spliygmic or pulse wave.
The rapid transmission of the pulse wave through the arteries
coincides with a momentary rise of blood pressure perceptible
to the touch, and a momentary acceleration of the blood-flow,
which, as we have seen, can be directly observed under the
microscope.

E. H. Weber (1850) was the first to make a thorough experi-
mental study of the laws of wave movement. For our purpose it
will be sufficient to consider the fundamental principles on which
the complex and delicate mechanism of the production of this wave
depend. At each outflow of blood from the ventricles, the walls
of the first section of the arteries expand in consequence of the
sudden impact, and then by elastic reaction produce the dilatation
of the succeeding sections by exerting pressure on the blood with
which they are filled. This elastic transmission of the wave is
repeated in the next section, and so on. Thus, it is the blood
expelled from the heart which causes the wave-like dilatation of
the vessel walls, while the elastic reaction of the walls consequent
on this dilatation propagates the wave.

The gradual diminution of the wave in its course through the
arteries until it disappears at the capillary threshold is an effect
of the growing resistance which it encounters at each ramification
of the vessels. The amplitude of the wave decreases by the same
laws as the average pressure in the arteries.

The velocity of transmission of the wave depends on the specific
gravity of the fluid, on the diameter of the vessels, on the thickness
of the vessel walls, and on its elastic coefficient. According to
Moens, it is inversely proportional to the square root of the specific
gravity of the fluid and to the internal diameter of the vessel, and
directly proportional to the square root of the thickness of the
walls, and their coefficient of elasticity.

By means of the graphic method it is possible to study every

viii BLOOD-STEEAM : MOVEMENT IN VESSELS 241

detail of the propagation of the pulse -wave in elastic tubes.
Besides the classical researches of E. H. Weber (1850), we have
the observations of Bonders (1859), Marey (1875), and Moens
(1880). In rubber tubes the rate of propagation of the wave
varies, according to different observations, from 10 to 18 m. per
second.

In an elastic tube, thrown into tension by a fluid, and closed
at both ends, it is possible to evoke negative as well as positive
'waves, generated not by the sudden rise, but by the sudden fall of
pressure. It is only necessary to let a small quantity of fluid
escape suddenly from one end, or, after compressing the tube at one
point, suddenly to release the compression, in order to produce the
transmission of a wave, represented not by a dilatation but by an
undulatory depression. The velocity of propagation of the negative
wave is practically the same as that of the positive wave, and
essentially obeys the same law.

When the rubber tube in which the positive or negative wave
is produced is not so unduly long that the wave has died out at
the extreme end, the first wave propagated through the tube gives
rise to a second reflex wave, which traverses the entire tube in the
opposite direction and interferes with the primary wave, since
it has the same velocity of transmission.

In elastic tubes which branch like the arterial system, the
waves generated in the principal vessel' extend to all the com-
municating branches, and at the points at which the vessels branch,
where there is a sudden rise of resistance, there is invariably a
formation of reflex waves. These reflex waves are, however, lost
when they reach the main vessel, which in consequence of its
capacity and the great elasticity of its walls acts as a kind of
extinguisher to the small waves reflected from the secondary
vessels. The aorta must act in this way in regard to the reflex
waves from the bifurcation points of all the other arteries
(Marey).

Having thus discussed the general laws of pressure, circulatory
velocity, and pulse-wave in the arteries, we must next consider
the most important data established by the study of these three
complex phenomena.

IV. The idea of measuring the blood pressure in the arteries
originated with Stephen Hales (1733). He connected the artery
of a horse with a long glass tube in order to see the height to
which the blood would rise. In this way he ascertained that the
arterial pressure was equal to a column of blood of 8 to 9 feet. He
further noted that the height of the column of blood in the
tube oscillated with the cardiac systole. Poiseuille (1828) replaced
Hales' piezometer by a U-shaped mercury manometer, which was
a great advance in practical method. To this Ludwig (1847)
added a float provided with a pen, which records every variation

VOL. i R

242

PHYSIOLOGY

CHAP.

of the mercury column on a rotating cylinder. This is another
immense advance, as the recording manometer was the first
application £>f the automatic graphic method, which has since
been employed in the most various directions, and has rendered
signal service to physiology. (Fig. 91 ; and Fig. 68, p. 207.)

FIG. 91. — Lud wig's kymograph. (Baltzar's type.) The movements of the drum are rendered
uniform by the clockwork of a Foucault regulator. The velocity of rotation is altered either
by pushing the little wheel on the axis of the drum nearer to or farther from the centre
of the vertical metal disc, which drives the drum by simple friction, or by adjusting the
clockwork of the regulator.

Ludwig's writing manometer or Kymograph is the classic
instrument by which the absolute value of the average blood pressure
of any artery can be directly obtained under natural conditions.
An anti- coagulant alkaline or peptone solution is introduced
between the blood and the mercury. If the manometer is con-
nected by a T-cannula with the artery, the flow of blood through
the vessel is not interrupted, and the resulting value gives
the lateral pressure obtaining in the branch vessel. For greater

vni BLOOD-STKEAM : MOVEMENT IN VESSELS 243

convenience, however, it is customary to join the artery to the
manometer by a simple cannula, ligatured to the central side of
the artery, so that the vessel is occluded. In this case the height of
the manometer column of course expresses the lateral pressure in
the arterial trunk from which the occluded vessel sprang. The
cannula may also be introduced in a peripheral, instead of central,
direction in the artery. In this case the manometer measures the
pressure either in the capillary network or in the other arterial
branches with which the artery, to which the cannula is peri-
pherally connected, anastomoses. For instance, a manometer
connected by a cannula with the central side of the dog's carotid
measures the lateral pressure in the aoria ; if, on the other hand,
the cannula is connected with the peripheral side of the same
artery, the pressure that obtains in the so-called Circle of Willis
will be obtained. In the first case, the pressure, according to

FIG. 92. — Tracing of arterial pressure in dog's carotid, recorded by Lud wig's kymograph.

(Marey.)

Steiner, may reach a value of 214 mm. Hg ; in the second, a
pressure of only 154 mm. Hg results. The first value represents
the lateral pressure that prevails in the trunk of the aorta at the
origin of the carotid ; the second, the pressure in the arterial Circle
of Willis, which communicates directly with the peripheral trunk
of the carotid.

As can be seen in Fig. 92, the tracings recorded with Lud wig's
manometer exhibit small oscillations corresponding with the single
cardiac systoles, and more ample and less steep oscillations which
correspond to the respiratory movements.

The latter will be considered in relation to the mechanics of
respiration ; as regards the pulsatory oscillations it must be noted
that the mercury, owing to inertia, is incapable of faithfully
recording the rapid variations of arterial pressure produced by
each wave of blood expelled from .the heart, so that Ludwig's
instrument is the least fitted for the study of the form of the
pulse-wave. Since this instrument is intended to determine the
value of the average blood pressure, the pulsatory oscillations are
a superfluous complication which can easily be excluded by a
constriction in the manometer at one point, as proposed by

244 PHYSIOLOGY CHAP.

Setschenow, which prevents the mercury from making any rapid
movement. In the manometer represented in Fig. 68, p. 207, this
is easily effected by adjusting the screw placed at its lower end
to the required point. The mercury column is then practically
immobile between the highest and lowest points of the pulsatory
oscillations, and the apparatus merely records the average blood
pressure.

In order to obtain as true a record as possible of even the
most rapid oscillations of blood pressure, the elastic manometer or
tonometer was invented, in which the mercury mass is replaced by
a spring or other elastic body, having but a small mass, and being,
therefore, more free from the errors due to inertia, and better
adapted to follow accurately the finer details of the pulsatory
oscillations of pressure. The history of the modifications and
gradual perfecting of the elastic manometer are of merely technical
interest. We must confine ourselves to mentioning the hollow
spring manometer of A. Fick (1864), constructed on the same
principle as Bourdon's metal manometer, employed in steam-
engines, and the metal manometer of Marey, which is constructed
on the principle of the aneroid barometer. In 1885 Fick invented
another flat spring manometer, which is simpler and more sensitive
than the preceding. The entire apparatus is reduced to a slender
tube ending in a small capsule, closed by a rubber membrane,
capable of small excursions which are transmitted to a flat steel
spring. By this method it is possible to reduce the movements of
the column of fluid in the tube connected with the artery to a
minimum, which facilitates the transmission of the more rapid
oscillations, and avoids the inconvenience of coagulated blood at
the point of the cannula. In order to magnify the oscillations of
pressure transmitted to the spring, and to record them on a
rotating drum, it is fitted with a long, light lever made from a
straw. Hiirthle perfected this manometer of Fick's by some
accessory contrivances, which made its application easier and more
certain, and confined the fluid between artery and manometer to
'the lowest possible minimum in order to transmit the variations
of pressure more rapidly and faithfully. Of course both Fick's
manometer and that of Hiirthle must be empirically graduated
by a mercury manometer in order to show absolute pressures.

Still better than a steel spring, however, for obtaining true
curves of the pulsatory oscillations of pressure, is the tonometer
formed of elastic guttapercha, the simplest type of which is Marey
and Chauveau's sphygmoscope (Fig. 66, p. 205) in connection
with their writing tambour (Fig. 63, p. 201). In order to diminish
the mass of fluid communicating with the artery, Hiirthle reduced
Marey 's tambour to a small capsule, covered with a resistent
rubber membrane ; its excursions were magnified by a long and
very light lever, while the capsule, by omitting the sphygmoscope,.

viii BLOOD-STKEAM : MOVEMENT IN VESSELS 245

was placed in direct connection with the artery. This is Hiirthle's
rubber manometer. Since the rubber membrane easily perishes,
Gad substituted for it a thin metal plate. Finally, v. Frey
gave the most practical form and shape to the entire apparatus,
combining the maximum of sensitiveness with stability and
permanence. He called it a meted tonograph (Fig. 93).

More recently (1904) Ducceschi has described a still simpler
method, by which the tracings of the normal blood pressure in the
carotid of dogs and rabbits can be recorded. After isolating a
sufficiently long tract of this artery in the neck, he divided it
between two ligatures, putting the central end in direct com-
munication with the isotonic lever of a myograph by means of an
inextensible thread, and counterbalancing the tension with an
adequate weight. In principle this method is the same as that
employed by En-
gelmann to record
the pulsations of
the- frog's heart
(see next chapter),
and its author gave
it the name of
method of suspen-
sion of the artery,
just as Engelmann

p n 1 1 P rl TIIG f Vi P Fl°- 93.— Von Frey's metal tonograpli, in which the rubber membrane
cailea iff replaced by a metal plate.

method of suspen-
sion of the heart. It is evident that the pressure of the blood,
exerted on the closed trunk of the carotid, must distend it in
correspondence with the average pressure and the rhythmical
oscillations due to the rhythmical beat of the heart (longitudinal
locomotion and arterial pulse).

Since these methods all involve the opening of an artery, and
introduction of a cannula, they are only practicable on man in
certain surgical operations (amputations) and other conditions
more or less removed from a physiological state. Methods have
accordingly been invented by which it is possible to determine
blood pressure without any surgical operation, and these can
therefore be applied to man. Vierordt (1855) was the first who
conceived the idea of measuring the blood pressure in an artery
indirectly, by ascertaining the weight required to suppress the
pulsations. Waldenburg, Potain, Talma, Koy and Brown
attempted the solution of the same problem. The sphygmomano-
meter of v. Basch (1876) is a small instrument designed for this
purpose, which has found wide acceptance with clinicians on
account of its easy applicability. It consists of a rubber finger-
stall filled with water, by which the radial or temporal artery i .
compressed. The finger-stall communicates by a rubber tube with

246

PHYSIOLOGY

CHAP.

a metal manometer, the indicator of which shows the pressure
exercised on the artery. When the indicator no longer shows
pulse - waves in the compressed artery, the internal pressure,
according to v. Basch, must (at any rate approximately) be equal
to the external compression. Tigerstedt rightly pointed out the
untrustworthy character of the values obtained by this method.
In spite of the improvements introduced by Eabinowitz (1881)
and Potain (1889) in the apparatus, and adopted by von Basch in
the latest model of his sphygmomanometer (1890), and notwith-
standing the many control experiments carried out by various

FIG. 94. — Tracings of pulsatory oscillations in volume of forearm, recorded with Marey's
sphygmomanometer. Shows the variations under the influence of increasing external
pressure, as indicated in cm. Hg at the side of each tracing. (Marey.)

authors upon animals (which show that while the pressure values
obtained from this instrument are unreliable, they still yield
results comparable inter se on the same individual), there are
certain obvious drawbacks to its practical application to man
which are not easily removed, and which render it untrustworthy.
The results may vary considerably in different cases, according to
the depth of the paniculus adiposus, the development of the
muscles, the arrangement and normal or sclerotic state of the
arterial walls, and in particular the tension of the aponeurotic
fascia which cover the arteries investigated, and more or less hinder
their compression.

The investigations initiated by Marey (1876), resumed in 1878,
and continued in Italy in 1895 by Mosso, were more successful.

vin BLOOD-STEEAM : MOVEMENT IN VESSELS 247

Marey's sphygmomanometric method consists in applying a
variable external counter-pressure not to a limited point of an
artery, but to the whole surface of a limb. He introduced the
forearm into a cylindrical vessel closed by a rubber ring, which
was filled under easily adjustable pressure with water, and
connected with a recording manometer, and then took a tracing
of the total pulsations of all the arteries of the forearm. He saw
that with gradual increase of hydrostatic pressure within the
cylinder, the pulsations increased during a first period, and then
diminished in a second, till they ceased entirely. In the tracings
of Fig. 94 it can be seen that the pulsations attain
their maximal excursion when the counter-pressure
on the forearm reaches 8 cm. Hg ; they then gradu-
ally diminish, and almost entirely disappear at a
counter-pressure of 19*5 cm. Hg.

In a second series of experiments Marey, in order
to make his method more practicable, gave up the
pressure on the whole forearm, and confined himself
to one finger of the hand, as seen in the apparatus
of Fig. 95. In order to make the pulsations of the

FIG. 95. — Marey's sphygmomanometer. It consists of a glass holder M, which is completely closed
after introducing the fore-finger, and communicates on the one hand with a capillary mercury
manometer b, on the other with a stout bag c, which is gradually compressed by a screw. The
whole apparatus should be filled with water, care being taken to avoid air-bubbles.

digital arteries more conspicuous, he employed a mercury mano-
meter of ^ mm. diameter, and limited himself to reading the
maximal and minimal values of the pulsatory oscillations on the
scale. This method again confirmed the preceding observation, to
the effect that the pulsations, with increase of counter-pressure,
are greater at first, and subsequently diminish and tend to die out.
But he also found that it was very difficult to obliterate them
completely, even when the counter-pressure reached a height of
28-30 cm. Hg, i.e. a value which is certainly higher than the
pressure exerted by the blood on the arteries of the fingers.
According to Marey, however, the value of his method lies in the
determination of the counter-pressure with which the most ample
oscillations of the mercury column are obtained. "At that moment,"

248 PHYSIOLOGY CHAP.

he says, " we learn theoretically that the vessels of the immersed
limb are wholly relaxed, and that their walls fluctuate as it were
indifferently between the internal pressure of the blood and the
external pressure of the water. The pressure of the blood, there-
fore, acts as though it were exerted directly upon the manometer."
This is as much as to say that we then obtain the true measure of
the lateral pressure exerted by the blood upon the arteries of the
finger. The arterial walls at that time must be in a state of elastic
equilibrium, since the internal force which makes for their dis-
tension is completely counterbalanced by the external force which
makes for their compression. If this criterion is applied to the
results shown in Fig. 94, the average pressure of the arteries of the
forearm in man is found equal to 8 cm. Hg, since the pulsations
reach their maximal amplitude when a counter-pressure of 8 cm.
Hg is put upon them.

Mosso continued and developed these investigations of Marey.
His sphygmomanometer is a modification of that shown in the
previous figure. He makes the counter -pressure act on four
fingers instead of on one, in order to obtain the total pulsations of a
larger number of arteries, and to record the tracings with a Ludwig's
mercury manometer. The following tracings, obtained by Mosso
and Colombo, are very instructive, the effects of various degrees
of compression of the four fingers under normal conditions being
compared with the tracings obtained from the same person after
a warm bath (Fig. 96).

As might be expected, the average pressure sinks on account
of the relaxation of the vessels due to the warm bath, and falls to
20 mm. Hg. At the same time the height of the pulsations after
the bath increases considerably, showing that they do not depend
on the internal pressure of the blood, but are in inverse ratio with
the degree of tonic contraction of the vessels. Evidence for this is
found in the fact that when the vessels of the fingers are strongly
contracted (as often happens in winter), it is impossible to obtain
the slightest sign of pulsation with Mosso's sphygmomanometer.
This is a disadvantage which renders the instrument applicable
only to a limited number of persons, and which is avoided by
returning to the original method of Marey, i.e. that of applying
compression to the whole forearm.

Starting from Marey's original method, Hiirthle (1896) intro-
duced some interesting modifications which deserve notice.

Both in Marey's and in Mosso's apparatus it is necessary in
measuring the lateral pressure prevailing in the arteries of the part
of the body examined, to increase or lower the external counter-
pressure repeatedly, in order to discover at what strength of counter-
pressure the maximal pulsations are obtained. With Hlirthle's ap-
paratus, on the contrary, the observation is continuous, and there is no
need to vary the counter-pressure applied at the outset to the forearm.

vni BLOOD-STEEAM: MOVEMENT IN VESSELS 249

He starts with the production of artificial anaemia by an

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Esmarch's bandage in the forearm and part of the upper arm, and
ties a ligature round the latter. He then introduces the anaemic

250 PHYSIOLOGY CHAP.

extremity, as far as half the forearm, into a glass cylinder, connected
on one side with a pressure bottle, on the other with his spring
manometer. An ingenious apparatus that is absolutely air-tight
fixes the end of the cylinder to the forearm. After the cylinder
has been filled with water and the connection with the pressure
bottle closed, the ligature is taken off; the blood from the artery
then flows into the limb and drives some of the water against the
manometer, which records a pressure equivalent to that exerted by
the blood streaming into the artery. Since the spring manometer
permits only small excursions, the quantity of blood entering the
artery of that part of the arm which is enclosed in the cylinder
will also be small. Hiirthle takes it to be not more than 10 c.c.,
which is certainly not sufficient to restore circulation in the vessels
of the limb. He therefore concludes that the values recorded by
his apparatus represent^ not the simple lateral pressure, but the
total arterial pressure (total head) which would obtain if the large
artery of the forearm were opened, and directly connected with
the manometer.

Hiirthle has not, up to the present, published any control
experiments that justify his conclusions, and there are good
reasons for doubting whether he has really succeeded in completely
obliterating all the vessels of the forearm, so as to interrupt
the circulation in the vessels of the interosseous space. The
external pressure is not readily transmitted to this space, since the
two bones are connected by strong aponeuroses, which make this
cavity a box with rigid walls that yield little to pressure greater
even than that of the largest arteries. It is therefore probable,
in consequence of the incomplete stoppage of the circulation, that
Hlirthle's apparatus does not register the total head, but merely a
pressure head which is not of the same value as the lateral pressure
of the blood normally circulating in the vessels of the forearm, but
increases in proportion with the sudden restriction of current-bed
in the greater part of the lirnb that is under investigation.

From the clinical standpoint these methods of Marey, Mosso,
and Hiirthle involve too complicated an apparatus, requiring no
little skill on the part of operator as well as patient, to ensure
success. Moreover, they only determine the lateral pressure in
arteries too small and too remote from the heart to give the
physician any adequate expression of the energy with which the
heart is acting under various morbid conditions.

Eiva-Kocci (1896) accordingly invented a simple and easily
applied sphygmomanometer, which measures by the manometer
the external counter-pressure required to block the progress of the
pulse-wave in one of the larger branches of the aorta, e.g. in the
brachial artery. The measurements obtained with this instrument,
which express the total pressure head (i.e. the lateral pressure plus
the velocity head) in the brachial artery, express the values of the

viii BLOOD-STEEAM : MOVEMENT IN VESSELS 251

lateral pressure that prevails in the aorta or innominate artery,
according as the apparatus is applied to the left or to the
right arm.

Kiva-Eocci's sphygmomanometer is an ingenious modification
of the method of v. Basch. The elastic finger-stall is replaced by
a hollow rubber ring (made inextensible by a cloth cover) which
fits round the arm and is connected with a mercury manometer
(Fig. 97). Air is then blown into the hollow ring by an ordinary
spray bellows, which becomes inflated and compresses all the
vessels of the limb, while the mercury rises in the tube of the
manometer. If more air is gradually forced in, so that the
mercury rises evenly, there
comes a moment at which
the radial pulse disappears.
The height of the mercury
column at that moment
represents the total head of
pressure supported by the
brachial artery during the
interruption of the circu-
lation in the arm, which
value approximates to that
of the lateral pressure in
the aorta, as demonstrated
by experiments with arti-
ficial circulation in rubber
tubes, or in the brachial

arteries of
body, as well
periments On

P
arterieS OI

rabbits.

the dead
by ex-

as

the
ClOgS

Crural FIG. 97. — Riva-Rocci's sphygmomanometer. a, Hollow

and

rubber ring covered with silk ; m, mercury inano-
meter with only one arm ; i, double rubber bellows.

As the sphygmomanometer of Eiva-Eocci is applied to the
upper arm, which has only one central bone, the muscles, when
fully relaxed, behave exactly like a fluid, and convey the pressure
of the elastic ring perfectly to all the vessels of the upper arm, as
was not the case when the apparatus was applied to the forearm.
The chief detects of v. Basch's sphygmomanometer thus seem to
be excluded.

In order to obtain utilisable values with the Riva-Rocci apparatus, it is
essential that the subject whose pressure is to be measured should be
absolutely quiescent. In this way only can the value of the individual minimal
pressure be obtained, uninfluenced by the disturbances produced by emotional
influences, which vary to a considerable extent in the same person, with the
same stimulus. The armlet is fastened preferably to the middle of the right
arm by means of the ligature attached from behind to the lower part of the
arm, so that it is applied to it like a flat bandage.

The forearm is bent towards the upper arm, care being taken that all the

252

PHYSIOLOGY

CHAP.

muscles of the latter, especially tlie biceps, are entirely relaxed. With one
hand the operator feels the brachial or radial pulse at the bend of the elbow
joint, and with the other he slowly blows in air, until every trace of pulse is
lost. If the manometer scale is now read for the exact point at which the
pulse disappeared without reappearing during maintenance of the pressure,
the desired pressure value will be obtained.

Another simple apparatus, easy to handle, which with certain modifica-
tions is making its way like the preceding into medical practice, is Gartner's
tonometer (1899). This apparatus (Fig. 98) to some extent combines the
principles of the methods of Hiirthle and of Biva-Rocci. It also consists of
a hollow ring, with an internal wall of rubber, which can be gradually
inflated by an elastic spray bellows, and communicates on the other hand
with a mercury manometer, on the scale of which the pressure values may be

read. It is fixed round one of the
fingers, and measures the total
pressure of the blood in the arteries
of that finger. The method is as
follows. First, as in Hiirthle's
method, the phalanx of the finger
to be experimented on is made
anaemic, by applying an elastic
bandage to the finger or by slipping
a rubber ring over it ; or, on the
principle of an Esmarch's bandage,
rolling down from the point of the
finger to the root, over the differ-
ent joints in succession, a fine
strip or tube of, elastic rubber.
The finger is then introduced into
the pneumatic ring of the appara-
tus, so that the ring embraces the
phalanx, and air is blown in from
the elastic bag by turning the screw
of the compressor until the pres-
sure of the tonometer exceeds that
of the blood. The bandage which
FIG. 98.— Gartner's tonometer. Consists of bellows produced anaemia is then removed,
(4,0ooSrn,SrrrtheW± Sn^ ™* the pressure withmthe tone-

a one-armed mercury manometer (m), on meter Slowly reduced by turning

the other with a hollow ring (a) which slips the screw that compresses the elas-
"111*"-'11*"' tic W in the opposite direction,

until the internal pressure exceeds
the external counter-pressure, and the blood re-enters the arteries of the
finger as shown by the flushing of the pulp, or subjectively by the return of
the pulse. The value read at that moment on the manometer scale is equal
to the total pressure of the blood in the digital arteries.

V. Volkmann concluded from the data which he collected in
order to determine the variations of normal blood pressure in
various species of animals, that the height of pressure is in no
sort of ratio with the size of the animal. The lateral pressure in
the dog's aorta, e.g., fluctuates between 130 and 180 mm. Hg, in
the rabbit between 100 and 130 mm. Hg, in the horse between
150 and 200 mm. Hg. This seems paradoxical at first sight, but
is not so when we reflect that the work of the heart depends not
only upon the magnitude of resistance or pressure, but also upon

vin BLOOD-STEEAM : MOVEMENT IN VESSELS 253

the volume of blood driven by the heart into the arteries at each
systole. Even if blood pressure in the horse differs little from
that of the rabbit, yet the horse's heart does far more work,
because it throws a far greater quantity of blood into circulation.

The mean blood pressure in man cannot differ much from that
of the larger mammals. We may think of it as varying approxi-
mately from 130 to 150 mm. Hg, values which come very near
those which Faivre (1850) determined directly upon the femoral
'and brachial arteries in amputations.

The values obtained by Marey and Mosso by their sphygmo-
rnanometric methods reach no such high figures (80 to 90 mm.
Hg) ; yet it must be remembered that they only represent the
average total pressure of all the arteries, large and small, of the
forearm, or of the fingers of the hand.

The mean arterial pressures, as determined by Eiva - Eocci
with his sphygmomanometer, oscillated in healthy individuals
between 125 and 135 mm. Hg. They corresponded to the
greatest total pressure obtained in the brachial artery of man
when a simple cannula is introduced in a central direction, and
connected with Ludwig's kymograph. As we have said, these
values represent approximately that of the lateral pressure that
prevails in the aorta.

The blood pressure sinks very little between the aorta and the
larger branches of the arteries, in which it is possible to introduce
a cannula connected with a manometer, because the resistance due
to the friction surfaces increases very little. Volkmann gives the
following data for dog and calf, which correspond essentially with
those obtained by Bernard, Marey, and others : —

Carotid of dog = 172 mm. Hg. Carotid of calf =116 mm. Hg.
Femoral „ =165 „ Femoral „ =116 „

Metatarsal „ =155 „ Metatarsal „ = 88 „

On the other hand, pressure falls rapidly in the small branches
of the arteries, where there are many ramifications, and in the
capillaries, where the friction surfaces are greatest. The values
obtained by v. Kries with Ludwig's method of counter-pressure
can only be taken as approximate. Generally speaking, we may
assume that pressure in the capillaries does not exceed ^-f- of
the aortic pressure (about 20-38 mm. Hg).

In the trunks of the veins nearest the heart, as in the in-
nominate, subclavian, and jugulars, there is on an average a
negative pressure, which according to Jacobsen may attain a
value of -0*1 mm. Hg, and is due to the aspiration exerted by the
lungs in consequence of the elastic tension into which they are
thrown during the expiratory phase. The pressure becomes
positive in the veins farthest from the heart and thorax. Accord-
ing to Jacobsen it amounts to 0*3 mm. in the external facial vein

254 PHYSIOLOGY CHAP.

of sheep, to 4'1 mm. in the brachial vein, and to 114 mm. Hg in
the crural vein.

In the pulmonary circuit the pressure cannot be determined
directly without opening the thorax, and giving artificial respira-
tion which produces a condition very unlike the normal. Here we
can only say that in the left branch of the pulmonary artery
Ludwig found a pressure = 29*6 mm. Hg in the dog ; = 17'6 in the
cat; =12 mm. Hg in the rabbit. The relation between the
pressures in the pulmonary artery and the aorta can be deduced
from the highest values which the pressure reaches during systole
within the two ventricles. According to Goltz and Gaule the
pressure in the pulmonary artery is to that in the aorta as
something like 2 : 5.

Blood pressure may vary very considerably not only in different
individuals of the same species, but also in the same individual under
different conditions, notwithstanding the regulatory mechanism
which tends to keep it constant. These variations depend on
those of the three main factors by which pressure itself is normally
determined : —

(a) The variations in the energy of the heart, i.e. in the
amount of blood driven in the time - unit through the arterial
system.

(6) The variations of resistance encountered by the blood in its
passage through the vessels.

(c) The variations of the total mass of blood contained in the
system.

The energy of the heart, and the work performed in the time-
unit, depend both on the frequency of its revolutions, and the
mechanical value of each of these. An increase in the frequency
of cardiac rhythm can be compensated by a corresponding diminu-
tion in the mechanical value of each revolution, and vice versa.
This mechanical value is dependent on the degree of systolic
evacuation, and the degree of diastolic filling. In brief, whatever
the determining conditions, an augmentation or diminution in the
quantity of blood driven through from the heart to the arteries in
the unit of time produces, ceteris paribus, a proportional increase
or decrease in blood pressure.

Variations in the resistance of the vessels exert the same
influence on blood pressure. Given the same energy of cardiac
function, a greater or less proportion of the driving force will, on
increase or decrease of vascular resistance, be expended on throw-
ing the walls into tension, which produces a corresponding rise
or fall of pressure.

Increased vascular resistance can, under physiological con-
ditions, be determined only by augmentation of the tonic con-
traction of the muscle cells, with which (as we shall see in the
next chapter) the middle layer of the vessel walls, particularly in

vni BLOOD-STEEAM : MOVEMENT IN VESSELS 255

the small arteries, is richly provided. The increased resistance to
the passage of the blood, provoked by the augmentation of vascular
tone, depends both on the degree of this augmentation, and on its
extension over a more or less extensive vascular area.

In like manner, the diminution of vascular resistance must, under
physiological conditions, depend upon a more or less pronounced
or diffuse paralysis or diminution of tone in the vessels. In the
next chapter we shall study the physiological adaptations for
regulating cardiac and vascular activity, and the processes by
which the central and peripheral variations of the circulation tend
to become compensated.

In order to determine the dependence of blood pressure on the
mass of blood contained in the system, it is obvious that the
effects on blood pressure of transfusion and bleeding must be
considered. This subject was studied by Tappeiner, and in an
exhaustive manner by Worin-Muller in 1873, in Ludwig's labora-
tory. The results of the experiments show that in the dog during
the increments in blood pressure produced by successive transfusions
of homogeneous defibrinated blood, or the corresponding decrement
produced by successive haemorrhages, the physiological limits vary
very little, far less than would be expected from the amount of
blood added to or taken from the system. Further, such rise or
fall in arterial pressure is of very brief duration, and therefore can
only be influenced to a minimal extent by increase or diminution
in transudations, and urinary secretions, through the capillaries.
There must, therefore, be some compensatory mechanism, which
tends rapidly to restore blood pressure to the normal, by producing
a dilatation or constriction of the small arteries and capillaries,
which adapts them even to very considerable alterations in the
blood content.

Pawlow's researches (1878), which confirm Worm - Miiller's
observations by another method, must also be noted. When a
dog was fed on dry bread or meat he found that blood pressure
fell 10 mm. Hg in an artery of the thigh, owing to the
dilatation of the intestinal vessels and digestive secretions. On
giving the same dog a large quantity of broth he found no rise of
blood pressure. There must, therefore, be some mechanism which
promptly reduces an increase or decrease in the amount of fluid
contained in the body to its normal limits.

Pawlow further showed on dogs that, during complete rest and
sensory inactivity, blood pressure from day to day does not alter.
On the other hand, it increases slightly after meals, and sinks
slightly in the morning. It regularly becomes lower after a warm
bath. The abrupt upward or downward changes in arterial
pressure are due to disturbances of vascular innervation (infra,
Chapter X.).

The results of a series of experiments which Colombo carried

256

PHYSIOLOGY

CHAP.

out in Mosso's laboratory with a sphygmomanometer applied to
the fingers of a healthy man are only partially in agreement with
Pawlow's.

He found that when a man is removed from all external and
internal influences liable to produce disturbance of the vasomotor
functions, the lateral pressure of the digital arteries fluctuates
constantly within 24 hours between a minimum of 65 and a
maximum of 100 mm. Hg (average 80-85). The greatest decrease
occurs after meal times, the greatest rise during hours most
removed from meals. The daily curve of blood pressure must
accordingly run an opposite course to that of pulse frequency and
temperature. As a matter of fact the pulse is accelerated when
arterial pressure falls, and becomes slower when it rises, which is
apparently the expression of some compensatory mechanism.

The depressor effect of meals is certainly due to active vascular
dilatation of the digestive organs, and possibly to the entrance of
a small amount of peptones into the circulation. Colombo found
that the highest fall of pressure (which may amount to 20. mm. Hg)
is apparent two hours after meals, when the absorption of the
products of digestion is beginning.

The introduction of a large quantity of milk, contrary to what
might be expected, produces a rise in pressure, in consequence of
the overloading of the circulation, which cannot apparently be
compensated by depression of the vascular tone.

Alcohol, chloroform, opium, warm baths, sleep, lower the blood
pressure ; cold baths and coffee raise it.

Gymnastics and massage of the limbs and back produce a rise,
massage of the abdomen a fall, in blood pressure, probably because
they influence the vascular tone in a different degree and in
different proportions.

The pressure in the veins, in consequence of their ready
distension, is less subject to fluctuation than arterial pressure.
Theoretically it may be assumed that all the circumstances that
produce a rise or fall in arterial pressure, cause, or may cause, a
change in venous pressure in the opposite direction. Venous
pressure is specially affected by : —

(a} Increment or decrement in amount of blood.

(6) Kespiratory movements (to be discussed later).

(c) Position of the body (according to the laws of hydrostatics).

VI. Observations on the velocity of the circulation have
been made in two opposite directions. On the one hand, it has
been attempted to determine the mean velocity with which the
blood moves in any given artery ; on the other, to establish the
form of the pulsatory changes of velocity.

At present we must confine ourselves to the methods employed
for ascertaining the first point.

By mean velocity of the blood in an artery is meant the length

viii BLOOD -STKE AM: MOVEMENT IN VESSELS 257

of the blood column that traverses the section of the said artery
in the time-unit, usually 1". It can easily be calculated when the
sectional area of the artery and the amount of blood that traverses
it in the time-unit are known.

The first to attempt the exact determination of this point was
Volkmann (1846). His method was adopted by Ludwig (1867)
who perfected Volkmann's haemodromo meter. His instrument (the
Stromuhr) permitted the repetition on the same animal, for an
indefinite number of times, of the determination of the mean
velocity of the circulation, so that its variations with changes of
experimental conditions can be investigated.

Lud wig's Stromuhr or haemo-
dromometer (Fig. 99) consists of
two glass receivers of equal
capacity (A, B), which com-
municate above by a U-bend,
in the centre of which there is
a tube opening to the exterior.
By means of this aperture the -
bulb A can be filled with oil,
and bulb B with physiological
saline, after which the aperture
is closed by a stop-cock. The
cannula a (which communicates
with the bulb A) is then con-
nected with the central end of
the artery, and the cannula b
(which communicates with the
bulb B) with its distal end. As Fl,..!M).
soon as the blood reaches the
stromuhr, it penetrates A and
drives the oil into B, when the
salt solution contained in the

latter is driven into the peripheral part of the artery. When the
blood has completely filled the 'bulb A, the two receivers which
are reversible upon the metal plate c are changed by a rapid half-
turn, so that A is now in connection with the cannula b, and B
with cannula a. The bulb containing oil is now again filled with
blood, and the oil once more driven into the bulb A, and so on.
If the number of turns in a given time are counted, then with
known capacity of the receivers it is easy to calculate the total
quantity of blood flowing in that time through the artery, from
which the quantity passing per second can be calculated.

Tigers tedt modified Lud wig's Stromuhr by substituting for the
two receivers a single, accurately calibrated glass cylinder, along
which runs a hollow metal ball. The pressure of the blood drives
this ball from one end of the cylinder to the other ; so soon as

VOL. I s

wig's haemodromometer or Mroinuhr.
A, B, (Mass bulbs of equal capacity ; «, 1>, can-
nulae to be connected with central ami periph-
eral trunks of artery ; c, metal plate fixed on a
support, on which the air-tight metal disc in
which the two receivers end can rotate.

258 PHYSIOLOGY

CHAP,

this occurs, the cylinder is reversed by a mechanism resembling
that of Ludwig's Stromuhr, and the ball moves in the opposite
direction, driving the blood before it.

We also invented a haemodromometer, which, with the utmost
simplicity of construction, presents the advantage of being able
to vary the capacity of the two receivers, which correspond to the
bulbs of Ludwig's apparatus, by employing two elastic bags in
a receiver full of water. The first two editions of this text-book
gave the description and figure omitted here in favour of the new
model constructed by Hiirthle, which has the further advantage of
automatically registering its movements.

Hiirthle 's haemodrompmeter (as shown in Fig. 100) consists
essentially of an inverted U-tube, in one branch of which there is
a cylindrical receiver containing a piston, which is easily movable
from the top to the bottom and the bottom to the top. The blood-
stream, which issues from the central end of the artery (carotid in
the dog), ascends by a branch of the said tube, penetrates the
cylindrical receiver, and, by lowering the piston, empties out the
fluid (artificial serum with which it was filled at the outset) into
the distal end of the artery.

When the ball reaches the extreme end of its course, the
experimenter at once reverses the blood current through the
cylinder by giving a half -turn to a disc beneath it by means of a
screw. The blood current will then flow into the cylinder from
below, driving the piston up, and turning the blood into the distal
end of the artery.

The reversal of the current is repeated each time the ball
reaches the top or bottom. The interval between one reversal and
the other expresses the duration of each filling and emptying of
the cylinder that measures the current. The excursions upward
and downward of the ball are transmitted by a system of pulleys
to a lever writing on the smoked paper of a rotating drum. A
Deprez signal simultaneously records the time on the same drum,
while an elastic manometer (Hiirthle) applied to the artery shows
,the pulsatory oscillations of the arterial pressure.

The tracings in Fig. 101 are reproduced from those obtained
by Hiirthle with his ingenious haemodromometer (reduced by one-
third), which serves at the same time for a spring manometer
recording the oscillatory pulsations in pressure and for an electric
time-marker.

These haemodromometric methods are certainly not free from
defects, and they give, not the normal absolute values of current
velocity in any given artery, but values as much lower than the
normal as the resistances artificially opposed to the passage of the
blood through the measuring apparatus are greater. Since, how-
ever, these new resistances are a fixed and constant coefficient,
they do not interfere with the value of the comparative results.

vin BLOOD -STEEAM: MOVEMENT IN VESSELS 259
On the other hand, the method still occasionally adopted after

FIG. 100.— Hiirthle's recording haemodrompmeter, partly schematic, partly in section, a, b, Can-
nula« connecting with central and peripheral ends of artery ; c, well-calibrated glass cylinder
into which the blood flows, pushing the piston now from above downward, now from below
upwards. The piston is connected by a thread passing over two pulleys, to the lever d,
which records on a rotating drum the movements of the piston, i.e. the filling or emptying of
the cylinder. Below the metal plate which supports the measuring cylinder is a movable
disc e, with handle, /, connected with the metal band g, which turns the disc 180°, reversing
the current and crossing the rubber tubes a' b'. Before applying the apparatus, the whole of
the tubing a, a', b, b', c is filled with physiological saline. This is effected by the tube h carry-
ing a tap, which is shut off when the tubes are completely filled.

Harvey (who first employed it to measure the velocity of the
circulation) is entirely fallacious, since it is based on the amount

260

PHYSIOLOGY

CHAP.

of blood which escapes in the unit of time from a divided artery.
In this case all the peripheral resistances which the blood has to
overcome under physiological conditions are artificially excluded.
Even when the lumen of outflow is artificially constricted (e.g. by
introducing a glass cannula of narrow bore) in order to build up a
resistance similar to that which the blood normally encounters, it
is impossible to obtain any correct values of current velocity, both
because we do not know if the resistance added is of the same
value as that subtracted, and because in any case the animal is
losing the Wood that flows out, which sets up quite abnormal
conditions.

Fio. 101. — Curve of velocity and pressure of blood in left carotid of a dog of 13 kgrms. (Hiirthle and
Tschuewsky.) The upper tracing is divided along the abscissa into six periods (Pi, Pn, etc.),
at which the current in the measuring cylinder was reversed. The spaces comprised between
the horizontal lines of the tracing correspond with 0 c.c. of blood. The curves of the second
level represent the pulsatory oscillations of blood pressure in the central cannulae of the
haemodromometer, and were recorded with a spring manometer. The bottom line gives the
time in seconds. The vertical line C.d.c. of the third period gives the moment at which the
right carotid was compressed, which produced an augmentation both of velocity and of pressure
in the left carotid, as shown in the tracing.

The experimental results obtained by Dogiel and Nicolaides
with Ludwig's stromuhr are somewhat meagre owing, no doubt, to
the very variable conditions that affect the velocity of current in
any given artery. They show that both in the carotid and the
femoral of the dog or rabbit the velocity may alter greatly from
one moment to another. Since the first determinations usually
show a higher value than the subsequent, it was conjectured that
this was due to a commencement of clotting at the insertion point
of the cannula. This supposition was, however, excluded, inasmuch
as the same fact was observed with blood that had been rendered
incoagulable by peptone injection, viz. that velocity diminished as
the experiment proceeded, more often in the carotid, less frequently
iii the crural artery.

vin BLOOD-STREAM: MOVEMENT IN VESSELS 261

The following are some of the data derived from Dogiel's
researches : —

Animal.

Duration of Observa-
tion in seconds.

Velocity in mm.;

Weight of
Animal
in kgrms.

Rabbit .

110

226-94

17

Dog .

80

733-349

23 '3

»

127

520-243

12-1

63

458-411

3'2

,, (division of vago - sym-

pathetic)

45

339-204

3-6

The -velocity of the blood-flow, which is essentially a function
of the resistances in that part of the circulation to which the
haemodromometer is applied, must rise and fall with the increase
and decrease of resistance. It is probable that the mere manipu-
lation necessary for inserting the cannula in the artery is sufficient
to -produce relaxation of it and its principal branches, thereby
determining an abormal rise of current velocity, which soon falls
again in consequence of the recovery of normal vascular tone.

Dogiel further showed that there may be a compensatory rise
in current velocity in the carotid on exciting the splanchnic nerve ;
this has no direct action on the carotid region, but since it
provokes contraction of the vessels in the abdominal viscera, it
increases resistance in a remote vascular region of considerable
extent. He also observed, when using two stromuhrs on the same
animal, that the velocity in the carotid and the femoral arteries
may vary now in the same, now in the opposite sense. This shows
the great adaptability of capacity in the various vascular regions,
the mechanism, of which will be studied in the next chapter.

Tschuewsky (1903), using Hurthle's recording stromuhr, has
made a great many observations on dogs, upon the mean velocity
of the blood in the different arteries, and under various experimental
conditions. The following table gives the average of his
results : —

Artery.

Experimental Conditions.

Average
Weight of

Average Average Blood
Diameter of , Pressure in

Average
Velocity in

kgrms.

Vessel in mm. mm. Hg.

mm. per sec.

Crural .

Nerves of limb intact

137

2-5 77

128

> >

„ cut

14-6

2'8 88

275

Carotid .

Vagus and sym-

pathetic intact

14'1

3-27 92-6

241/2

Erom this table it appears that the velocity is normally much
lower in the crural artery than in the carotid, and that after

262

PHYSIOLOGY

CHAP.

division of the nerves to the limb (paralytic vaso-dilatation) the
diminution of resistance due to relaxation of vascular tone may
cause current velocity to rise to more than double the normal.

Tetanic excitation of the nerve, on the contrary, increases
resistance by increase of vascular tone (vaso-constriction) and com-
pression of the vessels by muscular contraction, with consequent
diminution of velocity, as shown in the following table : —

Experimental Conditions.

Weight of
Dog in

Diameter of
Crural

Average Pressure
of Blood in Crural

Average Velocity
in Crural Artery,

kgrms.

Artery, mm.

Artery, mm. Hg.

mm. per second.

Before excitation .

11-2

2-45

8-'3 -0

201-7

During tetanisation of

sciatic nerve with

strong currents .

84-8

96-6 .

After-effect of excitation

81-5

236-5

The results of experiments to determine the effect of temporary
anaemia of different vascular regions due to compression of the
arteries are also interesting.

The following are examples : —

Average Duration

Average Pressure Average Velocity

Experimental Conditions.

of Compression
in seconds.

of Blood in caro-
tid in mm. Hg.

in carotid in mm.
per second.

I. Before compression

109-2

308-2

During compression of

carotid of opposite side .

23-3

114-2

394-6

II. Before compression

120-1

293-3

After temporary compres-

sion of arteries on the

side to which the liaenio-

dromometer has been

applied ....

21-0

127-0

411-7

From this table we see (a) the marked compensatory rise of
velocity on constriction of an adjacent area ; (V) the marked rise of
velocity after temporary anaemia of the vascular area on the same
side, owing to the diminution of peripheral resistance due to the
resulting vaso-dilatation.

As regards the mean velocity of the blood-flow in the veins, we
have already stated that it must be less than that in the corre-
sponding arterial region, in proportion as the total area of the
venous system is greater.

The velocity- of blood-flow in the axes of the capillaries can be
determined without difficulty under the microscope by measuring
the time taken by a red corpuscle to traverse a certain distance,

vin BLOOD-STREAM: MOVEMENT IN VESSELS 263

which can be measured by an ocular micrometer. The values
obtained with this method by different observers are shown in the
following table by Tigerstedt : —

Animal.

Velocity in mm. sec.

Observers.

Frog, abdominal muscle

0-28

Hales

Frog larva, tail .

0-57

E. H. Weber

Frog, interdigital membrane

0-51

Valentin

55 5 ) 55

0'2o

Vorkmann

Salamander larva, gill

0-36

Vierordt

Frog larva, tail .

0-40

A'olkmann

Fish, caudal fin .

0-12

Puppy, mesentery

0-80

-

The velocity of the red corpuscles in the capillaries of the retina
was ingeniously determined by Vierordt upon himself, by means
of their entoptic images. If we look without accommodating the
eye at a large clear surface, e.g. the sky, numerous shining points
appear which move one after the other by tortuous paths ; these
are the blood-corpuscles seen entoptically, owing perhaps to con-
centration of light upon their concave discs. Vierordt projected
these images upon a surface of 11-16 cm. from the eye, and there
determined the space traversed by a single corpuscle in the time-
unit. From this he deduced a velocity of 0'5-0*9 mm. per sec.
The values of the velocity of blood-flow in the capillaries is of
special interest, owing to the fact that it is possible from these to
deduce the approximate extent of the total area of the capillary
system. Since the velocity of the blood in the vascular system is
inversely proportional to its total area, we can calculate from the
area of the aorta and the velocity of the blood in the aorta and its
capillaries the total area of these last, inasmuch as the area of the
capillary system

_ area of aorta x velocity in aorta
velocity in capillaries

If we admit the value of 0*5-1 m. as the mean velocity in the
aorta and that of 0-5-l mm. in the capillaries per second, thus, with
an aortic area of 44 cm.2, we obtain the value of 8800-2200 cm.2 for
the total area of the capillary system (Tigerstedt)

VII. We must now pass on to the methods devised in order to
analyse the pulsatory oscillations of blood pressure, of current
velocity, and of the volume of the vessels. All three phenomena
are intimately related among themselves, and all depend on the
fact that the flow of blood from the heart to the arteries is not
continuous, but occurs in intermittent waves, which coincide with
the cardiac systole. We will begin by reviewing, collectively, the

VOL. I s a

264 PHYSIOLOGY CHAP.

observations made on these three phenomena in order subsequently
to compare the results.

The so-called sphygmographic methods have yielded perfect
sphygmograms, which give an exact graphic representation of the
pulsatile oscillations of pressure.

Even the ancient physicians, more particularly Herophilus,
Erasistratus, and Galen, recognised by touch some of the chief
characteristics of the arterial pulse, and the alterations in frequency
(pulsus frequens et rarus), magnitude (p. magnus et parvus), rate
of dilatation (p. celer et tardus), hardness or compressibility
(p. durus et mollis), regularity or irregularity of rhythm (p. inter-
mittens, altcrnans, intercurrens), and lastly, in the form of the pulse
wave (p. dicrotus seu bis feriens). But all these and many other
distinctions of pulse, as laid down by Galen, are founded far too

much on subjective
appreciation. Cusano
(1565) made a great
advance when ' he first
used a watch to count
the beats ; still greater
progress was made by
Vierordt (1855) who
first demonstrated the
possibility of register-
ing the pulse auto-
matically, although his

Fi<;. 102. — Marey's contrivance for transmitting the move- , , ,Fj

merits of the spring to the writing-lever of the sphygmo- SpiiygmOgraph did not

graph, m, Steel spring; >>, button compressing the artery, aiin«apr| \n rrivinrr

connected above with a little rod, of which the screw bites 8110066(1 in giving a

into the wheel of the axis a, which moves the lever I from f.riip liiftlirp of thp

above downwards in the direction of the arrow. ~ f"7 U

form ot the pulse-wave
or the pulsatile oscillations of arterial pressure.

The first sphygmograph which accurately recorded the form of
the pulse was that constructed by Marey in 1860, which found
ready acceptance among physicians owing to the elegance of the
method, and the exaggerated hopes of clinical advantage that were
founded on it. The essential part of Marey's sphygmograph was a
steel spring, pressed against the radial artery by a button, which
transmitted the pulsations to a long and very light lever, by which
they were recorded exactly, in a magnified form, upon a metal
plate covered with smoked paper, propelled at a uniform rate by
clockwork. Fig. 102 shows the mode of transmitting the move-
ments of the spring to the lever according to the most recent
improvements, and Fig 103 shows the complete instrument applied
to the forearm. The sphygmograms obtained with Marey's
sphygmograph may vary considerably under different conditions of
health and disease; but all have one characteristic feature — a
rapidly ascending and slowly descending period can always be

viii BLOOD -STEE AM: MOVEMENT IN VESSELS 265

distinguished. The former, produced by the pulse-wave which
starts from the aorta, usually reaches its culminating point
without interruption ; the latter, on the contrary, shows several

Fm. 103. — Marey's direct sphygmograph, applied to the radial artery.

oscillations, one of which (the second, expressed in a rise preceded
by a slight depression) is rarely absent in pulse tracings. It is
known as the dicrotic wave, and con-
sists in a negative wave (dicrotic
notch), immediately followed by a
secondary positive wave.

It has been proved by innumer-
able control experiments of Buissou,
Marey, Landois and others, that the
sphygmograms thus obtained do really
reproduce the form of the pulsatile
oscillations of blood pressure, and that
their constant dicrotisrn is no factitious
product of the registering apparatus.
Here we need only say that sphygmo-
grams obtained with the sphygmoscope
or other elastic manometers (Fig. 67,
p. 205) present the same dicrotic form.
Moreover, as Landois showed, it is
possible to obtain autosphygmograms,
by dividing the artery of an animal,
and directing the rhythmical jet of
blood against a rotating drum covered
with filter -paper (liaemautograpliy).
As shown by Fig. 104, the form of the
haemautogram agrees perfectly with
those from the sphygmograph and sphygmoscope : while the
dicrotic wave is even more apparent, this being the only really
important feature of the pulse curve that we need consider.

Since the dicrotic wave persists, and is even more pronounced
in autosphygmograms, it is proved to be the result of a positive

FIG. 104.— Auto-sphygmogram (Haem-
autogram) from posterior tibial
artery of large dog. (Landois.) p,
Primary wave ; (/, dicrotic wave.

266

PHYSIOLOGY

CHAP.

wave of central origin and centrifugal course — which excludes the
hypothesis still maintained by some, that it arises in a peripheral
and centripetally reflected wave. This last hypothesis is also
irreconcilable with the fact that the secondary positive wave is
nearly always preceded by a negative wave which, as we shall see
immediately, can only be of central origin.

FJC

105. — Sphygmograms from radial artery (,sV), and changes produced by inhalation of
ainyl nitrite (SV). (A. 1). Waller.)

The long experience of nearly half a century, during which
Marey's sphygmograph (or other sphygmographs which are only
modifications of this instrument) has been employed clinically, has
proved it to be of very little diagnostic value. We have for
many years insisted on this fact, and for the following reasons.

Fio. 106. — Marey's transmission Bphygraograph applied to radial artery. This only differs from
the direct sphygmograph in that the movements of the button of the spring are not trans-
mitted by a lever, but by a receiving tambour, which then transmits them to a second
tambour writing upon the revolving drum of the kymograph.

It is quite true that the sphygmogram is the true expression
of the form and magnitude of the pulsatile oscillations in pressure
in the artery to which the instrument is attached, but it is far
from representing their absolute values. Local arterial pressure is
indeed dependent on many variable factors ; on the tension of the
spring, the elasticity and tone of the arterial walls, the amount
and degree of torpor in the surrounding soft parts. From all these
causes, the size of the pulse, i.e. the amplitude of the sphygmogram,
is in no definite ratio either with the volume of blood driven
from the heart to the arteries at every systole, nor with the height

viii BLOOD-STREAM: MOVEMENT IN VESSELS 267

of pressure within the artery investigated ; it is only proportional

to the magnitude of the

local oscillations of the

pulse, which (as we saw

on p. 248) are, ceteris

paribus, in inverse ratio

to the tension of the ar-
terial walls. As a matter

Of fact, not only the prim-
ary, but also the secondary

dicrotic wave is lower

with greater, and higher

with reduced arterial

pressure. Not even this

fact, however, can be

taken as a general law,

since the varying degree

of contraction or relaxa-
tion in the artery explored

has great influence upon

the amplitude of the

sphygmic undulations.

In order to realise this,

we have only to consider the marked changes that appear in
the form and magnitude of the sphygmo-
gram after inhalation of amyl nitrite, which
immediately produces depression of arterial
tone (Fig. 105). The beats of the heart
become more frequent, and yet the amplitude
of the primary as well as of the dicrotic
wave increases.

Far more interesting and instructive, from
the clinical point of view, is the comparison
of the sphygniogram with the simultaneously
recorded cardiogram, as also the comparison
of two or more sphygmograms simultaneously
recorded from different arteries. For this
purpose, however, the direct sphygmograph
IDS.— Bdgren's sphygmo- is not suitable, and others with air transmis-
af receivTg^iSuht- sion musfc beresorted to. These are essentially
tached to a" semicircular identical with cardiographs, but are different

«™ng intended to tit round ./. • ,, • j! j j j?

neck. The pressure of in form, sin ce .they are intended for use on

FIG. 107.— Burdon-Sanderson's cardiograph, which can also
be used as a sphygmograph for the carotid, and a
pneumograph (Zimmermann's type). The apparatus rests
on three ebonite feet, which can be adjusted by screws.
It is fixed by a band to the thorax or neck, so that the
central button, which has a steel spring (the tension of
which can be altered by a screw), presses against the
spot at which the beat of the heart or carotid pulse is
most perceptible. The transmission by air of the move-
ments of the spring is effected through a receiving
tambour, the position of which in regard to the spring
can be regulated by a screw.

the exploring button upon
the artery is regulated by a
plate applied to the neck,
which stretches the spring

the several arteries. One of these trans-
mission sphygmographs is that of Marey

more or less according to the (represented in Fig. 106), for the radial
artery. A simpler model is that of Edgren
for the same artery. Burdon- Sanderson's cardiograph (Fig. 107)

268

PHYSIOLOGY

CHAP.

can be used for the carotid, femoral, or other arteries, as also
Edgren's sphygmograph, or any kind of tympanum with an
elastic membrane kept stretched by a spiral spring, and provided
with an exploring button in the centre, which can be pressed
against the artery to be examined (Fig. 108).

VIII. The comparison of cardiograms and sphygmograms
simultaneously recorded on the same revolving cylinder gives all
the data necessary to establish the chief characteristics of the two
tracings. Those of Fig. 109 were obtained by Edgren on a healthy
youth of twenty-five. The various features of the cardiographic
curve (a, b, c, d, e,f, g, h, i) are indicated by vertical lines. Since

FIG. 100.— Cardiograms (C) and sphygmoscrams (S) of carotid of a healthy subject of -2u. (Edgren.)
a, b, c, d, e, /of the cardiograms correspond with the «], foj, cj, </1; e\,f\ of the sphygmograms.

these are obvious, they need no further description. After what
was said in the previous chapter (Fig. 80, p. 224) we know that the
point a corresponds with the onset of systole, when the first sound
of the heart begins to be heard, and the point / with the onset of
diastole, when the semilunar valves, which have already been
closed at the systolic dead point, are thrown into tension, and the
second sound develops. In the sphygmographic curve of the
carotid the point coinciding with a shows no marked feature.
The primary sphygmic wave which starts from the arterial orifice
first reaches the carotid at the point V The interval ab', therefore,
represents the time taken up by the transmission of the pulse
wave from the arterial orifice to the carotid, plus the time of the
latent systole, i.e. that between the commencement of the con-
traction of the myocardium and the moment of the opening of the

viii BLOOD-STEEAM: MOVEMENT IN VESSELS 269

semilunar valves (point I of the cartographic curve). Since
the points &, c, d, e, f of the cardiogram correspond to the same
number of points on the sphygmogram at V, c, d', e',f, but all
with a delay, equal approximately to the interval aa', it follows
that this interval expresses the time occupied by the transmission
of the primary wave from the arterial orifice to the carotid, and
that the intervals ab, a'bf represent the time of latent systole.

The interval &c, which can hardly be seen on the cardiogram
as a slight drop in the curve, corresponds to the interval Vc'
marked by the sharply ascending curve of the primary wave.
The interval cd, indicated by a slight rise of the cardiographic
line, corresponds to the interval c'd', indicated on the sphygmogram
by a tract that is almost horizontal (the plateau}. The interval
de, corresponding to d'e', both on the cardiogram and on the
sphygmogram shows a slowly descending line : and the intervals
ef and e'f correspond in both curves with rapidly descending lines.

Leaving aside the features c and d which are less conspicuous,
and have only a dubious significance, it is evident, or at any rate
extremely probable, that the entire interval be represents the
period of systolic outflow or evacuation, during which the heart,
in consequence of the diminution in its volume, exerts a constantly
decreasing pressure on the intercostal space to which the cardio-
graph is applied. In the sphygmographic curve these periods are
represented by the interval Vc' in which the primary pulse wave
is traversing the artery.

The small interval ef coincides with the beginning of active
diastole, during which, owing to the diminished tension of the
cardiac muscle, the intercostal space on which the button of the
cardiograph rests, sinks in. This corresponds to the lines e'f of
the sphygmogram, which represent a true negative wave that pre-
cedes the secondary or dicrotic wave.

To understand the origin of this dicrotic wave it is enough
to consider that at the commencement of diastole an enormous
difference between aortic and intraventricular pressure arises : this
causes the blood column to gravitate towards the semilunar valves
which are already closed, throwing them into vibration so that
they develop the second sound, and set up the negative wave in
the artery, owing to their distension towards the conus arteriosus.
The sharp tension of the valves is succeeded by their elastic
reaction, which produces the positive dicrotic wave that follows
immediately on the negative wave. The great majority of physi-
ologists, including Grashey, Edgren, Hoorweg, Hiirthle, are
unanimous in accepting this explanation of the dicrotic wave. To
us its central origin appears conclusive, on account of the negative
wave that precedes it and can only be caused by the rapid
recession of the column of blood in the aortic bulb, which
•distends the valves and pushes them down towards the conus

270

PHYSIOLOGY

CHAP.

arteriosus ; — not by the reflux of a certain amount of blood from
artery to ventricle, to produce closure of the valves, as is arbitrarily
assumed by Edgren.

The points g, h, i, which are distinguishable on the long
descending shoulder of the cardiographic curve, of course find no
analogue in the sphygmogram, because after closure of the semi-

Fio. 110. — Comparison of synchronous sphygmograms of carotid (Nc) and of radial (.s'r). (Edgren.)

lunar valves changes of pressure within the ventricle can no longer
be transmitted to the arteries. Here we will only say that the
point g, which marks the lowest depression of the cardiographic
curve, very probably corresponds with the moment at which the
negative pressure in the ventricle exerts the maximum of aspira-

Sf

Fio. 111. — Synchronous sphygmograms of carotid (.Sic) and femoral (Sf). (Edgren.)

tion ; that the point h marks the moment at which active diastole
ceases, and passive diastole or the true rest of the heart begins;
and that finally the point i (which is usually, but not constantly,
visible in cardiographic tracings) points to the moment at which
presystole commences, causing a certain degree of passive dilatation
of the ventricle, as perceived in a gentle rise of the cardiograph
button.

When the rate at which the cylinder rotates is known, and the

viii BLOOD-STEEAM: MOVEMENT IN VESSELS 271

characteristics of the cardiographic and sphygmographic curves, as
described above, are well marked, the length in millimetres, and
corresponding period in fractions of a section, of the chief phases
of the cardiac cycle in man can easily be determined. It is well
to make these determinations from tracings obtained from one
healthy individual, with constant experimental conditions during
the research. The data thus obtained are of approximately absolute
value for the individual under observation, and are certainly far
more trustworthy than the average data derived from comparison
of results yielded by various individuals under varying experimental
conditions.

From the careful measurements taken by Edgreu upon a

Sr

FIG. 112. —Synchronous sphygrnograms of radial (X?-) and femoral (X/). (Edgren.)

healthy man of 25, whose pulse beat 70 times per minute, the
following values were obtained, which may be taken as the average
of ten successive cardiac revolutions : —

Period of tension ...
Period of efflux ....
Total duration of systole

- ab- 4'OV n
= be = 11-71

nn. = 0-U934 sect
, =0-2342

= tie =16-38

, -0-3276

= «/ = 2-60
= fa = 24-14

, -0-0520
, - 0-4828

= ea = 26-74

, -0-5348

= ««-43-12

, =0-8624

Total duration of diastole .

Total duration of cardiac revolution

IX. If the pulse of the carotid and radial, or the carotid and
the femoral, or the femoral and radial are registered simultaneously
as shown in Figs. 110, 111, 112, it is possible to determine with
great accuracy the time occupied in the propagation of the primary
wave V, or the dicrotic wave /', by deducing it from the delay
between the appearance of the two waves in the arteries most
remote from the heart. This delay is represented in the three
figures by the intervals W and f'f. If they are measured with
a millimetre scale, it will be seen that their length alters with the
difference between the two arteries of which the sphygmograms are
compared. It will also be seen that the wave b' appears simultane-
ously in the femoral and the radial, while the wave f appears with
a measurable delay in the femoral.

Edgren obtained the following results as the average of a
number of measurements of these intervals in sphygmograms taken

PHYSIOLOGY

CHAP.

on two healthy individuals 25 years of age. The delay between
the radial pulse and the carotid for the wave V — 3*93 mm. = 0*0786
seconds, for the wave/' = 3*96 mm. = 0*0792 seconds.

Since the distance from the semilunar valves to the point on
the carotid at which the sphygmograph was applied was 20 cm.
and to the corresponding point on the radial 80 cm., the time
difference found corresponded to a length of 60 cm. From these
data the time of transmission of the wave ~b' from heart to carotid
can l>e calculated :

3-93 : r = 60 : 20 ; x - 1'31 mm. =0-0262 seconds ;
<ind from heart to radial :

3-93 + 1-31 = 5-24 mm. = 0'1048 seconds.

By a similar calculation the propagation of the wave f from
heart to carotid is found to be :

3-96 : .r = 60 : 20 ; x= 1-32 mm. = 0-0264 seconds ;
and from heart to radial :

3-96 + 1-32 = 5-28 mm. = 0-1056 seconds.

Repeating the same measurements and calculations for the
single series of tracings obtained on the two young men, Edgren
obtained the results appended on the following table :—

Distance.

From heart to carotid I.

I
From heart to radial I.

II-

From heart to femoral I

Time of Transmission

of Primary Wave V.

of Uicrotic Wave J '.

d I.

1-31 mm. 0-0262 sec

|
1-32 mm. 0-0264 sec.

II. .

1-36

0-0272

1-36

0-0272 ,

I.

5-24

0-1048

5-28

0-1056 ,

II.

6-32

0-1064

5-32

0-1064 ,

•al I. .

5-50

0-1100

1 6-35

0-1270 ,

II. .

5'31

0-1062

6-32

0-1264 ,

From these data Edgren found it easy to calculate the rate of
transmission of the two waves, i.e. the distance they traversed in
•one second (the unit of time).

The results are given in the following table :—

Velocity of Transmission

Distance.

of Primary Wave.

of Dicrotic Wave.

From

carotid to radial

= 60 cm.

7-63 m.

7'53 m.

58 „.

7-32 ,,

7-32 ,,

From

carotid to femoral

= 52 „ . .

6'20 „

5-20 „

»

52 „ .

6-59 „

5-40 „

••

vin BLOOD-STREAM: MOVEMENT IN VESSELS 273

These results agree well with those of previous authors, notably
with those of Keyt. The differences depend principally on the
respective degree of elasticity of the arteries explored, and the
respective height of the mean blood pressure within them ; the
greater the elasticity of the arteries, the higher the blood pressure,
and the greater will be the velocity of wave transmission (Moens,
Grunmach, Keyt).

Edgren's results, like the earlier conclusions of Keyt, lead us
to think that the velocity of the wave in the vessels is higher in
the upper limbs than in the lower. Edgren further found by
comparing the velocity of the primary and the dicrotic wave that
it is less in the latter. The difference, which can hardly be
detected betwreen heart and radial artery, is conspicuous between
the heart and the femoral artery, as appears from the above tables.

The wave-length can easily be calculated from the velocity of
transmission of the waves and from their number, since it is in
direct proportion to the rate of propagation (h) and inversely
proportional to the number of vibrations (ri), according to the

equation A - -. If with Edgren we reckon the time of systolic

outflow = 0'23 seconds, the number of vibrations in one second will
be equal to 5*75, and their velocity of propagation (taking the
average of that calculated by Edgren for the primary wave) is
equal to 6-93 m. per second. Accordingly the wave-length

6'93

l'20 m. Since in an adult the distance from heart to

small arteries of the foot is a little greater, these arterial tracts of
the body are the only ones long enough to accommodate the entire
length of the pulse wave, and the end of the wave usually passes
the orifice of the aorta when the front of it has already reached
the peripheral arteries (Tigerstedt), so that these pulsate during
the whole of the systolic outflow.

We know experimentally how many influences react on the
pulse-rate ; e.g. the lowering of blood pressure and dilatation of the
vessels produced by heat, by amyl nitrite, and by profound narcosis.
The pulse is perceptibly slowed, as can be measured not merely in
artificial narcosis on animals, but also in physiological sleep, and
on man. Patrizi compared the velocity of the pulse wave in the
waking state and in deep sleep, by means of experiments on a boy
of 13, as also the pulsations of the brain (the boy had lost part of
the bony substance of his cranium) and of the feet.

Velocity of propagation in waking state, 6-50 in. per second.
Velocity of propagation in sleep, 5-77 in. per second.

X. The pulsatile oscillations of pressure in the sphygmograms
must be distinguished from the pulsatile oscillations of velocity,
which are also determined by the rhythmical undulations of the

VOL. I T

274

PHYSIOLOGY

CHAP.

heart. Vierordt (1858) was the first to construct an apparatus
for the study of these oscillations. Vierordt's haemotachometer is
based on the principle of the hydrostatic pendulum, used by

FIG. 113. — Chauveau's haemodrometer. Left-hand figure shows the^instrument as a whole ;
right-hand, a vertical section of it. (Explanation in text.)

engineers to measure the rate of a stream of water. His method
was perfected and developed by Chauveau (1860), who constructed
a very ingenious recording apparatus on the same principle, which
he termed a haemodromograph.

Fig. 113 shows this apparatus as a whole on the left, and in

vm BLOOD-STREAM: MOVEMENT IN VESSELS 275

section on the right. The tube TT is intended for insertion in
the carotid artery of a horse or other large animal ; L represents
the bar of the pendulum which ends in a very light plate or disc
p, dipping into the axis of the blood-stream. The bar of the
pendulum passes at m through a rubber membrane, which acts
as a pivot to the pendulum, and is then prolonged externally till
it joins a Marey's air tympanum. The tube TT has a narrow
longitudinal cleft along which the terminal disc of the pendulum
•can move, in accordance with the oscillations of current velocity ;
these are reversed at the membrane of the receiving tambour,
which again transmits them to a tambour with a writing lever.
No blood can enter the groove in which the bar of the pendulum
oscillates freely, because it is connected with an external space
filled with an alkaline solution through the side tube B, and then
closed with a clamp. The sphygmoscope S is applied at the side
of the tube TT, and records the oscillations of pressure on a
revolving cylinder by means of a second writing tambour which
acts synchronously with the first.

Just as sphygmograins do not give absolute values of oscilla-
tions of blood pressure, so the tachygrams or dromogranis recorded
by Chauveau's haeniodromograph yield only relative values of the
oscillations of current velocity above and below the zero line,
which is reached when there is no movement, because the disc of
the pendulum is under equal pressure on both sides. In order to
ascertain the absolute value of velocity and its oscillations, the
apparatus must be graduated. Chauveau did this by sending a
stream of water through it, of which the outflow was regulated
until the deflections of the pendulum attained the maximal,
minimal, and mean values obtained on applying the apparatus to
the carotid of the horse. It is then easy to determine the velocity
corresponding to these points, by calculating it from the diameter
of the arteries, and from the respective amount of outflow, obtained
with different degrees of deflections of the pendulum.

Chauveau and his pupils Bertolus and Leroyenne were able to
determine that the velocity of the blood-flow amounted to 520 mm.
per second in the carotid of the horse during systole, to 220 mm.
during the dicrotic wave, and to 150 mm. during diastole.

When the carotid is ligatured on one side, a compensatory rise
of velocity is visible in the other carotid. During the masticating
movements also, in consequence of a dilatation of the vessels of
the masticatory muscles and salivary glands, there is an increase of
circulatory velocity in the carotid, which may become five or six
times greater than the initial value. When any considerable
vascular dilatation is produced by dividing the spinal cord, the
rate of flow is considerably augmented during systole, but becomes
extremely low during diastole. At the end of diastole the
velocity is greater in the peripheral than in the central arteries ;

276 PHYSIOLOGY CHAP.

at the commencement of systole, on the other hand, it increases
more in the central than in the peripheral arteries.

It is no less interesting to examine the features presented by
tachygrains as compared with sphygmograms simultaneously
recorded. Fig. 1 14 gives an instructive example of these tracings
as obtained by Lortet, another of Chauveau's pupils. Point 1
corresponds to the moment in which the primary systolic wave, on
reaching the carotid, produces a simultaneous rise in pressure
and in velocity. At point 2 the pressure reaches its maximum
when the velocity has already begun to fall, in accordance with the
increase of elastic tension in the distended artery, by which the
velocity of the movement of the blood is proportionately moderated

FIG. 114. — Tachygram (V) and sphygmogram (P) registered simultaneously on carotid artery of
horse, with Chauveau's haemodroinogiaph. (Lortet.)

and depressed. Point 3 probably corresponds to the moment at
which the systolic efflux ceases and the closure of the semilunar
valves ensues, and point 4 to the moment at which the latter are
thrown into tension owing to the beginning of diastole, which
makes the blood column gravitate and recede against the already
closed semilunar valves, and in the sphygmogram determines
the negative wave that precedes the positive dicrotic wave. This
interpretation is in fact confirmed by the course of the tachy-
graphic curve, which at points 3 and 4 drops below the zero line
indicating a backward movement of the current, followed rapidly
by the dicrotic rise. In the entire interval from 4 to 1 (which
corresponds approximately to the periods of peri- and pre-systole),
the pressure curve shows a slowly falling line, which expresses the
decrease of arterial pressure in proportion as the elastic reaction
of the artery drives the blood into the capillaries and veins.
Velocity also decreases at the same time, but more slowly.

XL During the passage of the pulse wave through the arteries,

vm BLOOD-STKEAM : MOVEMENT IN VESSELS 277

it produces a transverse dilatation and elongation, which are in
relation with the pulsatile oscillations of pressure. The lengthening
of the arteries produces a movement of the vessels at each wave
of blood that traverses them, as is clearly visible in arteries
ligatured after amputation. Normally, however, since the arteries
are not free to elongate in the longitudinal direction, they become
laterally curved when rectilinear, and increase their curvature if
(as in old people) they have a winding course ; and when (as in
the aortic and pulmonary area) they form a free arch with a short
radius of curvature, the curvature tends at each systolic wave to
change, and to assume a longer radius, by a mechanism similar to
that of the metallic manometer of Bourdon.

The elongation of the arteries, since it is plainly visible, was
known to the older surgeons ; the transverse dilatation on the
other hand is a less obvious phenomenon, so that in the eighteenth
century some of the clinicians (De la Mure in particular) denied
it altogether, and held that the arterial pulse perceptible to touch
is the effect of simple vascular locomotion. Spallanzani (1773)
was the first to demonstrate the pulsatile dilatation of the aorta
in the salamander by an ingenious experiment. " The aorta " (he
wrote) " pulsates in its entire length, and in pulsating it dilates,
but not equally in all its parts. Where it arches, its diameter is
increased by a third, but elsewhere it increases only about a
twentieth. Although my eye informed jne that in the pulsations
the increase in diameter or bulging of the aorta occurred more or
less at each point of the circumference, I employed the following
method to illustrate it : — I passed the aorta through a small open
metal ring which, when closed, was of slightly larger diameter than
the aorta. When the aorta dilated in its pulsations, the empty
space between it and the ring became smaller ; when it was con-
stricted the space became larger. I then diminished the capacity
of the ring. Now, where the aorta bulged, that is where there
was the greatest dilatation, the circular space was lost during the
cardiac systole, being filled in every direction by the dilated
vessel : this proved decisively that the aorta in pulsating dilated at
all points of its circumference " (Dei fenomeni della circolazione,
Dissertazione terza).

In proof of the same phenomenon, Poiseuille (1828) introduced
a length of a large artery into a long chamber, having at both
ends a circular hole of the same diameter as the artery it was
to receive. The cover of the chamber (which could be closed so
as to become water-tight) was pierced by a vertical glass tube
provided with a millimetre scale. After the chamber containing
the artery had been filled with fluid, the fluid could be seen to rise
in the tube at each systolic wave, and to fall at each diastole.
Poiseuille measured the increase in arterial diameter by the highest
point of the rise.

278

PHYSIOLOGY

CHAP.

This experiment of Poiseuille was the starting-point for the
construction of the apparatus known as the plethysmograph,
because it serves to register the content, i.e. the variations in
volume, of any organ, owing to the dilatation and constriction of
the vessels it contains. It is easy to see that where the different
organs or parts of the body are highly vascular, the total
movements of passive or active dilatation or constriction of all
the arterial branches they contain must produce very consider-
able variations in volume.

In order to estimate these variations in volume, Piegu (1846)

introduced a limb into a vessel
filled with lukewarm water and
closed completely, save at a
point through which passed the
vertical tube intended to show
the changes in volume. He
described the changes in volume
depending on cardiac, as well as
those depending on respiratory
rhythm. Chelius (1850), who
was not acquainted with the
previous investigations of Piegu,
investigated the changes in
volume of a limb by the same
method, and with the same
results.

Ch. Buisson (1862), who dis-
covered the graphic method by
means of air transmission to a
writing tambour, subsequently
perfected by Marey, was the first
who applied it to the plethysmo-

for recording rapid changes of volume of OTapllS of PiegU and ChellUS.
the hand, which are transmitted to a tarn- c A -.-,• -, /., o/»r»\ -i.i_ Ar-
bour with highly sensitive lever. A. Fick (1868), with the same

object, connected the water-tight

chamber in which the forearm was enclosed with a recording
water manometer, which directly recorded the pulsatile changes in
volume of the investigated limb upon a revolving cylinder.

A. Mosso (1874-75) described another ingenious plethysmograph,
with which he intended to record in absolute values the changes
of volume in an isolated organ or a limb. Owing, however, to
the sluggishness with which the recording apparatus functions,
it is incapable of following the rapid passive changes due to the
cardiac rhythm, while it is able to record the slow changes in
volume due to the active contraction and dilatation of the vessels,
which are entirely independent of cardiac rhythm. We shall
return to this in Chapter X.

Fia. 115. — Francois -Franck's plethysmograph,

A'

viii BLOOD-STKEAM : MOVEMENT IN VESSELS 279

Frangois-Franck (1876) made some useful modifications in. the
details of Buisson's apparatus, giving the apparatus the form of
Fig. 115. The flask placed in front of the rubber tube, which
joins the plethysmograph with the writing tambour, cuts out the
oscillations of the fluid along the vertical tube. The method and
instrument afterwards used by Mosso (1880) for recording the

FIG. 116. — A', Plethysmogram of forearm in fasting state.; A, the same, in same individual, after

a meal. (Mosso.)

pulsatile changes in the volume of the forearm, to which he gave
the name of hydrosphygrnograph, is very similar.

Among the various results of more or less importance obtained
by the plethysmographic method, we can here only refer to the
form of the curves depending on the pulsatile oscillations in
volume of the part explored, i.e. to vascular plethysuiograms and
their interpretation.

FIG. 117.— V, Plethysmogram of hand taken with apparatus of Fig. 115, the oscillations of th"
column of fluid being suppressed by the bulb interposed between the exploring apparatus and
the recording tambour. (Fr.-Franck.)

Vascular plethysuiograms are very similar to sphygmograms,
and exhibit the same principal features, including dicrotism, as
shown in Figs. 116 and 117. Still they cannot be identical since,
as we have seen, sphygmograms are obtained with an apparatus
which by means of a tense spring exerts pressure on the artery
investigated, depressing its lumen to a greater or less extent; while
plethysuiograms, on the contrary, depend solely on the alterations
in volume of the forearm or hand, all external pressure being as
far as possible excluded. Since the flow of blood in the veins is
continuous and uniform, it is clear that the changes of volume in

280

PHYSIOLOGY

CHAP.

the limb can only depend on variations in the blood-stream, or the
velocity with which the blood flows into the arteries at different
moments of the cardiac cycle. It is possible from the different
inclinations of plethysmographic curves to the axis of the abscissa
to construct the velocity curve (as Tick did), and thus to derive
the tachygram from the plethysmogram.

To illustrate this conversion of volume ciirve into velocity
curve, we enlarged the first plethysmogram of Fig. 117 by means
of a projection apparatus, subsequently reducing the ordinates by
half. This gave the curve represented by the fine line in Fig. 118;
which has the same form as the plethysmogram of Fig. 117 would

FIG. 118.— The tine curve is the first plethysmogram of Fig. 117 enlarged and drawn out.
The black curve is the tachygram, constructed graphically by, measuring the degree of inclina-
tion of the different sections of the plethysmogram. (Luciani.)

have assumed had it been recorded on a drum rotating at double
speed. From the plethysmogram thus transformed we have
graphically constructed the tachygram represented by the black
line of Fig. 118, which has a very similar course to that of the
tachygram recorded by Chauveau and Lortet with the haemo-
drornograph (Fig. 114). It must be noted, however, that the
tachygram thus derived from the plethysmogram does not give
absolute values of oscillations in velocity, and that the abscissa oo
corresponds not to zero velocity but to the moments in which the
volume of the forearm was unvaried, because the arterial inflow at
that moment balanced the venous outflow.

In order graphically to transform plethysmograms into tachygrams, the
ordinates of which represent the inclination of the different sections of the
first curve, the following method must be adopted. At any point P of the
plethysmogram draw the tangent to the curve ; measure the trigonometric

viii BLOOD-STKEAM : MOVEMENT IN VESSELS 281

tangent of the angle which this makes with the positive direction of the
axis of the abscissa, and then erect upon the point of the axis of the abscissa
corresponding to P an ordinate proportional to the measured trigonometric
tangent Fick has given a very practical method of determining these
tangents.

XII. Having thus analysed the principal phenomena relating
to circulatory pressure and velocity, it is necessary to consider a
scheme for combining them synthetically. With this object Fig.
119 shows in a single diagram the most important facts of the
circulation in the arteries, veins, and capillaries. In the arteries

Artery.

Capillary.

Vein.

FIG. 119.— Synthetic diagram of progressive variations in area of blood current, pressure, and
velocity, in the three main sections of the systemic circulation. (Gad and Fredericq.) The
schema does not show the respiratory and vasomotor oscillations of pressure and velocity.

the circulatory area (represented by the total section of the vessels)
increases slowly at first from the aorta to the small arteries, and
then rapidly from the small arteries to the capillaries. Both the
pressure and the velocity curves exhibit the same general course.
The pulse and the cardiac oscillations of velocity in the arteries
diminish slowly from the aorta to the capillary threshold.

In the capillaries, where the circulatory area becomes
maximal, pressure continues to diminish slowly, and velocity
becomes minimal and constant.

In the veins the area again decreases, rapidly at first, then
more slowly to the mouth of the venae cavae, where, however, it
is more extensive than at the aortic orifice ; pressure decreases
constantly, becoming negative in the intrathoracic veins ; velocity,
on the other hand, increases more slowly from the farthest

282 PHYSIOLOGY CHAP.

capillaries to the venae cavae, where, however, it is lower than in
the aorta. The intra- and extra- thoracic veins nearest the heart
show gentle pulsatile oscillations, either of pressure or velocity,
which coincide with the presystole and systole of the right heart.

If we consider the great velocity with which the wave move-
ments, produced by the intermittent outflow of blood from the
heart, are propagated through the arteries, it is evident that they
have no connection with the mean velocity of the circulation, i.e.
with the time required by a drop of blood or a corpuscle to
traverse the whole vascular circuit and return to its starting-point.
" Unda non est materia progrediens,sed forma materiae progrediens."
In this expressive sentence E. H. Weber does not deny that the
passage of the sphygmic wave through the arteries is accompanied
by an acceleration of the flow, and is thus an adjunct to the
circulatory movements ; he only intended to make a sharp dis-
tinction between the average velocity with which the blood streams
through the vessels and the rate of transmission of the pulse wave,
which is essentially a form propagated in a fluid.

In order to measure (at least approximately) the duration of
the entire circulation, E. Hering (1829) invented a method which
consisted in the injection of a harmless and easily recognisable
substance into the jugular vein of an animal, after which a sample
of blood was taken from the jugular vein on the opposite side at
intervals of five seconds (as marked by a metronome), and tested
for the injected substance. He selected ferrocyanide of potash,
since its presence, even in minimal quantities, can be detected by
an iron salt, in the presence of which Prussian blue is formed.
The results which he obtained on the horse were confirmed at a
later time by Vierordt (1858), and applied to other animals, by a
method which was a little more exact in regard to measuring the
intervals between the extraction of the different samples of blood.

It was found from the best of Bering's experiments on horses
that the blood required 26*2 sees, (on an average of nineteen
experiments) to pass through the entire circulation from one
jugular vein to the other. This path from one jugular to the
other is one of the shortest that a drop of blood can take, in order
to return to its starting-point after traversing the entire system.
If, on the other hand, the ferrocyanide is injected into a crural
vein, and the blood from the crural vein on the other side tested, the
path is considerably longer, and more time is required. Vierordt 's
work shows, however, that the time difference between these two
paths is very small, so that the blood in the larger arterial and
venous vessels circulates very rapidly, any marked delay first
occurring in the capillaries and the smallest vessels.

The discovery that the average time of circulation varies
among the different mammals, and that it is shorter in small than
in larger animals, is certainly among the most important results of

vin BLOOD-STKEAM : MOVEMENT IN VESSELS 283

Vierordt's many observations. When, further, we compare the
time of circulation with the number of heart-beats required to
complete it, we arrive, according to Vierordt's experimental data,
at the fact that twenty-six to twenty-nine pulsations are necessary
in every animal, independent of the mass of its body, to drive the
blood through the whole circulation from one jugular to the other.
This is seen from the following table : —

Animal.

Time of Circulation
in seconds.

i Pulse Frequency
per minute.

Number of Pulsations
in One Circulation.

Rabbit ....

7-46

220

26-1

Goat . . .

14-14

110

26-0

Dog ....

167

96

267

Horse (Hering)

31-5

55

j

28-8

As regards the time of the circulation in man, Vierordt thinks
it probably stands midway between that of the dog and the horse,
i.e. he estimates it = 27'1 sees., which with a pulse-frequency of 72
per minute corresponds to 27'7 heart-beats.

These data for the circulation time obtained by the methods of
Hering and Vierordt express not the mean velocity with which
the blood circulates in the vessels, but rather the maximal
velocity, i.e. that of the axial lines of the fluid flowing through the
vessels (see p. 189). V. Kries (1887) accordingly proposed to
reduce Vierordt's figures by half, to obtain the value of the average
velocity of the circulation. By the laws of hydrodynamics, the
mean velocity of a fluid traversing a tube must be equal to half
the greatest velocity of the axial current. Tigerstedt, however,
pointed out that the theory of the passage of fluids was only
applicable to the capillaries on the assumption that the stream of
fluid is free from solid particles, which depress the value of the
maximal velocity in the axial current. We know that the
erythrocytes which move in the axial current are so large that
they almost fill the capillary lumen, hence the mean velocity
in the blood capillaries must certainly be somewhat more than
half the maximal velocity. Still it can be positively affirmed that
the average time of circulation must be less than that given by
Bering's method.

BIBLIOGRAPHY

In addition to Bibliography at the end of Chap. VII. (p. 231) see :—
E. H. u. W. WEBER. Wellenlehre auf Versuche gegriindet. Leipzig, 1825.—

Observationes anat. et phys. Lipsiae, 1825. — Ber. d. sachs. Gesell. d.

Wissenschaften, 1850.— Arch. f. Anat. und Physiol., 1851-1853.
VOLKMANN. Die Hamodynamik. Leipzig, 1850.
BONDERS. Physiologic des Menschen. Leipzig, 1859.
A. FICK. Medicinische Physik. 2nd ed. Braunschweig, 1866.
LANDOIS. Lehre vom Arterienpuls. Berlin, 1872.

284 PHYSIOLOGY CHAP, vm

MA KEY. Traveaux du lab. Paris, 1875-1878.

MOENS. Die Pulscurve. Leiden, 1878.

A. Mosso. Ricerche sfigmografiche, R. Accad. delle scienze di Torino, 1878. R.

Accad. dei Lincei, 1887.

GRASHEY. Die Wellenbewegung elastischer Rbhren. Leipzig, 1881.
A. FICK. Die Druckcurve und die Geschwindigkeitscurve in der A. radialis des

Menschen. Wurzburg, 1886.

VON KRIES. Studien zur Pulslehre. Freiburg, 1891.
A. Mosso. Sphygmomanometre pour mesurer la pression du sang chez 1'homme.

Arch. itah.de biologie, 1895.
HURTHLE. tjber eine Methode zur Registrierung des arteriellen Blutdrucks

beim Menschen. Deutsche med. Wochenschr., 1896. Beschreibung einer

registrierenden Stromuhr. Pfliigers Arch., xcvii., 1903.

RiVA-Rocci. Un Nuovo Sfigmomanometro. Gazzetta niedica di Torino, 1896-97.
M. L. PATRIZI. II Progredire dell' onda sfigmica nel sonno fisiologico. Arch. ital.

de biol., xxxvii., 1897.
DUCCESCHI. Un Nuovo Metodo di sfigmografia. Arch, di fisiol. del Fano, i.,

1904.
TSOHUEWSKY. Uber Druck, Geschwindigkeit und Widerstand in der Strombahn

der Art. carotis ecc. Pfliigers Arch., xcvii., 1907.

Recent English Literature : —
.1. H. M'CuRDY. The Effect of Maximum Muscular Work on Blood Pressure,

Amer. Journ. of Physiol., 1901, v. 95.
L. HILL. On the Residual Pressures in the Vascular System when the Circulation

is arrested. Journ. of Physiol., 1902, xxviii. 122.
R. BURTON-OPITZ. Muscular Contraction and the Venous Blood -Flow. Amer.

Journ. of Physiol., 1903, ix. 161.

R. BURTON-OPITZ. Venous Pressure. Amer. Journ. of Physiol., 1903, ix. 198.
0. H. BROWN and C. C. GUTHRIE. The Effects of Intravenous Injections of Bone-
Marrow Extracts upon Blood Pressure. Amer. Journ. of Physiol., 1905, xiv.

328.
P. M. DAWSON. The Lateral "Blood Pressures" at Different Points of the

Arterial Tree. Amer. Journ. of Physiol., 1905-6, xv. 244.
T. LEWIS. The Influence of the Venae Comites on the Pulse Tracing, with

special reference to Valsalva's Experiment and Dicrotism ; a note on

Anacrotism. Journ. of Physiol., 1906, xxxiv. 391.
T. LEWIS. The Factors influencing the Prominence of the Dicrotic Wave. Journ.

of Physiol., 1906, xxxiv. 414.
0. RIDDLE and S. A. MATTEWS. The Blood Pressures of Birds and their

Modification by Drugs. Amer. Journ. of Physiol., 1907. xix. 108.
T. LEWIS. Studies of the Relationship between Respiration and Blood Pressure.

P. i. and ii. Journ. of Physiol., 1908, xxxvii. 213, 233.
E. C. SCHNEIDER and C. A. HEDBLOM. Blood Pressure, with special reference to

High Altitudes. Amer. Journ. of Physiol., 1908, xxiii. 90.

CHAPTER IX

PHYSIOLOGY OF CARDIAC MUSCLE AND NERVES

CONTENTS. — -1. Intrinsic processes by which cardiac rhythm is determined and
regulated. 2. Extrinsic chemical conditions of cardiac activity. 3. Effects ot
ligation and section on different parts of the heart. 4. Automatic or reflex
activity of heart. 5. Myogenic or neurogenic origin of cardiac rhythm. 6.
Evidence for these conflicting theories. 7. Special mode in which cardiac muscle
reacts to external stimuli. 8. Regulation of cardiac rhythm by nervous system :
inhibitory or diastolic nerves. 9. Accelerator or systolic nerves. 10. Theory of
anabolic action of diastolic nerves and katabolic action of systolic nerves. 11.
Afferent nerves of heart or other parts of the body which influence cardiac rhythm.
12. Nerve-centres for cardiac nerves ; their tonic excitability, and theory of
regulation of cardiac rhythm. Bibliography.

THE mechanical functions of the heart and vessels, as discussed in
the last two chapters, are modified by a variety of oscillations or
changes. Between certain limits these changes not only come
within the scope of normal vital activity, but also satisfy the
physiological necessity for adapting both the general velocity of
circulation, and the distribution of blood in the several parts of the
body, to the different external conditions and temporary needs of
the whole organism, or of its several organs or tissues.

The physiological changes in the activity of the heart consist
in increased or diminished frequency or force of its beats ; the
physiological changes in the activity of the vessels consist in their
dilatation or constriction (particularly in the small arteries), as
determined by the expansion or contraction of the muscle cells of
which they are constructed.

Even to the lay mind, it is obvious that these modifications
and adaptations of the activity of the heart and vessels depend
essentially on the nervous system, which is the supreme regulator
of all important vital functions. From the fact that the heart
responds to the psychical emotions by various modifications of its
activity, sprang the old Aristotelian belief that it is the seat of the
soul — a belief still surviving in popular ideas and expressions. The
fact that the emotions readily produce blushing and pallor of the
countenance shows that the nervous system is capable, independent
of the circulatory centre, of modifying the blood supply to the
several vascular regions.

285

286

PHYSIOLOGY

CHAP.

With the object of determining the limits of this regulatory
activity of the nervous system as exactly as possible, we shall in
the next two chapters discuss the better ascertained and more
important facts of human physiology, with respect to the physio-
logical conditions that underlie the activity of the heart and
vessels.

I. As shown in Chapter VII., the mechanical activity of the
heart is due to the regular sequence of three different states in its
muscles — contraction, expansion, and rest. In order to obtain a
clear idea of the origin, succession, and propagation of these three
states in the different segments of cardiac muscle, we must return

to this subject and
attentively study
the exposed heart of
the living frog or
tortoise (Fig. 120).

On cutting the
fraenuni, which at-
taches the posterior
wall of the ventricle
to the dorsal surface
of the pericardium,
and lifting up the
heart, we see that
the contraction com-
mences along the
venae cavae, and
spreads from these

H • \^ y R ' \v '' ^ / to tne smus venosus

in which they unite.
From the sinus
venosus, which opens
into the right
cle, th<

ventricular groove ; P, P', pulmonary veins ; M, L, left and right spreads tO the tWO
superior vena cava ; JV, inferior vena cava ; R. coronary vein. * . ,

auricles ; from the
two auricles it passes to the ventricle; and from the ventricle,
lastly, to the bulbus arteriosus, which contracts actively in the
frog, as first noted by Spallanzani. The contraction or systole of
the heart thus takes the form of a wave, which originates in the
afferent vessels and passes to the heart, where it spreads peristaltic-
ally from auricles to ventricle, leaving the heart by the efferent
vessels.

It should, however, be noted as a fact of great importance that
the peristaltic wave of contraction does not proceed uniformly, but
undergoes a delay or block at the junction between the sinus and
the auricles, the auricles and the ventricle, and, lastly, at that

FIG. 120.— 1 and 2, Anterior and posterior aspects of frog's heart.
At, Auricles ; V, ventricle ; A, A, rarai of aorta ; Ba, aortic bulb ;
Sv, sinus venosus; Vci, vena cava inferior; Fes, vena cava
superior; Vp, pulmonary vein; Vh, hepatic vein. 3 and It,
Anterior and posterior aspects of tortoise heart. A, A', Pulmon-
ary arteries; B, B', left and right aorta; D, D', left and right
subclavian arteries ; H, hemi-animlus of bulb ; /, auriculo-

ix CARDIAC MUSCLE AND NERVES 287

between the ventricle and the bulbus arteriosus. It therefore
follows that when the auricles begin to contract, the sinus begins
to expand; when the ventricle enters systole, the auricles are
commencing diastole ; when, lastly, the systole of the bulbus
arteriosus begins, the ventricle is entering diastole. The two
active phases (systole and diastole) are followed by the state of
rest or functional pause, which in the same way appears earlier
in the sinus than in the auricles, and in the auricles than in the
ventricle, with the resting phase of which the cardiac cycle or
revolution is complete.

These phenomena, which are easily detected on the frog or the
tortoise, are in complete agreement with those which can be observed
under greater difficulties in warm-blooded animals. In these,
too (as we have seen), the wave of contraction arises in the
large veins, which, as they have no sinus venosus, open directly
into the auricle : from the auricles it is propagated peristaltically
to the ventricles, where it is arrested, since these have no contrac-
tile bulbi arteriosi. In warm-blooded animals, too, the wave of
contraction encounters a block, or momentary delay, at the passage
from auricles to ventricles, so that the diastole of the auricles
coincides with the commencement of ventricular systole, a neces-
sary condition for the perfect functioning of the cardiac pump.

From these fundamental phenomena arise all the complex
problems relating to the physiological conditions of the cardiac
functions. On what does the rhythmical \action of the heart
depend ? What are the external chemical conditions indispensable
to its activity ? Is its rhythm of a reflex nature, dependent on
extrinsic conditions or stimuli, or is it automatic in character,
dependent on intrinsic conditions or stimuli within the heart ?
Is it a function of the nervous system, or simply a property per-
taining to the cells of cardiac muscle ? Is the peristaltic contraction
wave propagated by way of the nerves or by the muscle cells ?
Why does the wave of contraction arise in the venous paths that
lead to the heart ; and on what do the blocks or brief delays, to
which it is subjected on passing from one segment of the heart to
the other, and which are of such great importance to its mechanical
functions, depend ? These are the fundamental problems which
have to be examined.

METHODS OF STUDYING CARDIAC MOVEMENT

Cardiac movement must be studied either on the exposed heart in situ, or on
the fully isolated heart. The frog's heart isolated from the body is capable,
provided it be protected from drying in a moist chamber, of continuing its
normal activity for> some time (several days), and thus represents the most
accessible object for the study of cardiac movements. For this reason the
methods employed in the graphic registration of these movements were
especially contrived for the frog's heart. Observations of the surviving heart

288

PHYSIOLOGY

CHAP.

of warm-blooded animals are, on the contrary, impossible, except under

certain special conditions, and acquaintance with these conditions is one of

the most recent acquisitions of scientific technique.

A. Cold-Blooded Animals. — In order to obtain graphic tracings of the

cardiac movements in the frog or any other cold-blooded animal, three

different methods may be em-
ployed. Of these there are
various forms, the most im-
portant being : —

(a) Tonographic Methods. —
These consist essentially in
the use of a small mercury
manometer, which records
the oscillations of the internal
pressure of the frog's heart in
relation to the phases of its
activity. The apparatus re-
presented by Fig. 121 fulfils
all requirements for studying
the mode in which the activity
of the heart exhausts itself,
when excised from the animal,
filled with a nutrient fluid,

\ / and exposed to constant dia-

__J L. 1 stolic pressure at a given

\!^ I^ Yl / II temperature. The heart is

tied to a simple cannula
(Fig. 122, A) introduced into
the cavity of the ventricle
through an opening 111 the
sinus venosus. Owing to its
structure, it is easy to study
the effect of successive liga-
tures applied at different

121.— Luciaui's tonographic apparatus for recording heights of the auricles, when
the beats of the heart, when isolate^ and^attachedtp the heart ig fixed in the t(mo_

apparatus. Since

cannula at different heights of the auricles (semi
schematic), a, 'Reservoir of serum or other nutrient graphic

fluid, closed by Muriotte's method so as to keep the the'same nutrient fluid leaves

tilling and pressure of the heart constant ; b, valvular ,, , , -,

apparatus, closed during systole ; c. tap for interrupting the heart at each systole and

communication between the reservoir and the heart ; d, re -enters it at each diastole,

cannula to which the heart is tied, fixed to appara- ^1.^ ro,,,^.,! nf fi,0 c^lntir»t,

tus ; e, small vessel full of serum, which can be raised L

during the experiment, so as to bathe the whole of the can only be effected slowly

outside of the heart ;/, small mercury manometer, pro- jyyr diffusion through the

vided with float, which records the beats of the heart on J . /• -i S ,,-,,

the revolving cylinder with a glass pen. supernatant fluid, and filtra-

tion through the vessel walls.

This is a great drawback when the heart is to be kept for any length of time
under constant and normal conditions of nutrition. Under these circum-
stances it is necessary to replace the simple cannula by the two-way cannula
of Kronecker, figured in 122, B. An improvement on Kronecker's apparatus
is that of Williams (Fig. 123). This provides for the circulation of the nutritive
solution, by the complete separation of the fluid which enters, from that
which leaves, the heart, by means of two valves for its entrance and exit.
If the frog's heart is to be attached to the apparatus by a cannula introduced
into the ventricle through the aortic bulb, it is necessary to supplement
Kronecker's irrigation cannula by a very fine connecting tube, as shown in
Fig. 122 C.

The tonographic method introduced by Oehrwall (1896) is much simpler
By this it is possible to obtain simultaneous tracings of the activity of the

IX

CAKDIAC MUSCLE AND NEKVES

289

right auricle and the ventricle of the frog. No artificial valves are required
to separate the vessel containing the nutrient solution from the tonographie
apparatus, since the auriculp- ventricular valves of the heart itself are utilised
for the purpose. As shown in Fig. 124, the heart is attached to two cannulae,
one of which is tied to the aorta so that the valve is unable to perform its
function, the other to the sinus. The two cannulae communicate on the one
hand with the vessel containing the serum or nutritive solution, on the other
with two separate elastic tonographs similar to small Marey's capsules, which
record the oscillations of pressure in the right auricle and ventricle as trans-
mitted by the air. When disconnected from the reservoir by applying a
couple of pressure forceps at the

points indicated in the figure, A B C

the heart is made to beat in
presence of a small quantity of
fluid which circulates continu-
ously. When, on the other
hand, the forceps are undamped,
so as to open communication
with the reservoir, the whole
of the fluid present is perfused
through the heart. In the first
case the curves recorded by the
two tonographs are naturally
more ample, because they repre-
sent the total pressure developed
within the heart ; in the second
case they are less ample, because
the lateral pressure is recorded.

(b) Plethysmographic Methods.
— These aim at recording the
variations in the volume of the
cycle,
vari-
ous ways to the heart of the frog
or the tortoise by Frangois-
Franck, Roy, Gaskell, and
Williams. As shown in Fig.
123, plethysmograms of the
frog's heart are most simply
obtained by a slight modifica-
tion in Williams' apparatus, the
heart being placed in a small

heart during the pulsatory cy
They have been applied in v£

FIG. 122. — A, Simple cannula (Luciani) for frog's heart,
natural size. Consists of glass tube a, joined to rubber
tube b, which connects it with the manometer, and
has various metal rings (c) at the end, 2 mm. apart,
by which ligatures can be applied to the heart at
equal distances. B, Two-way cannula (Kronecker)
composed entirely of metal divided into two arms,
c, b, which unite externally into one arm d, divided
internally by a septum as shown in section at e. The
arm a is connected with the chamber for the serum ;
the arm b with the recording manometer. The metal
wire c serves as electrode, in the electrical stimula-
tion of the heart. The fluid expelled by the heart
at each systole is partially turned out, so that fresh
serum enters the heart at each diastole. C, Cannula
adopted in Williams' apparatus. The same two-
way cannula, as above, with the addition of a small,
simple metal cannula b, which is introduced into
the ventricle by the bulbus aortae.

and connected with a Marey's

111 a

closed cylinder empty or filled with
tympanum.

(c) Myographic or Gardiographic Methods. — By these we can record the
modifications in the external form of the heart, produced by cardiac systole
or diastole. These methods have been applied in a variety of ways. A light
lever may be placed directly upon the ventricle, or two levers, one on the
ventricle, the other on the auricles, when the magnified movements due to
changes in form of the heart (Marey's double myograph for heart of frog and
tortoise) can be read off. An ingenious modification of this method is repre-
sented in Fig. 125 (Marey's pince myographique). Gaskell introduced, a
method of suspension with which he obtained interesting results. It con-
sisted in fixing the heart at the auriculo-ventricular groove by a screw-clamp,
which could be easily adjusted. The apex of the ventricle and tip of the
auricle are attached by silk threads to very light levers, placed respectively
above and below the heart, which are pulled upward or downward during
systole, and record the magnified movement on a revolving cylinder.

VOL. I U

290

PHYSIOLOGY

CHAP.

Engelmann's suspension method (Fig. 126) is simpler as well as more reliable.
The cardiograms which it records (independent of the differences in form
and amplitude due to modifications in loading and length of lever) always
exhibit marked anatricrotism, i.e. the ascending curve rises to the summit in
three shoulders, and falls rapidly in a single line, as shown on Fig. 127.
With a signal, made by a writing lever, worked with the finger, the moment
at which the systole and diastole of the sinus (Ss Sd), the systole and diastole
of the auricles (As Ad), the systole and diastole of the ventricle (Vs Vd),
and the systole and diastole of the bulbus arteriosus (Bs Bd) commence can

Fio. 123. — Left : Williams' tonograph for recording movements of frog's heart ; excised and
attached to cannula, inserted into the ventricle by the bulbus aortae (semi-schematic). A
reservoir of serum, s, communicates from below with the cardiac cavity by the valve v, which
opens in diastole and closes in systole. A second valve v', which opens in systole and closes
in diastole, leads the serum back to the reservoir s. The manometer is put in communication
with the heart by means of an arm of the second valvular apparatus, and traces on the revolv-
ing cylinder the lateral pressure of the fluid coming from the heart. Right : Portion of Williams'
apparatus substituted for the little cup that encloses the heart, when it is desired to see the
changes of volume during the beats. If the small chamber containing the heart is left empty,
and the end of the curved arm of the manometer connected with a highly sensitive Marey's
tambour, the apparatus is converted into a cardiac plethysmograph.

be accurately enough determined. The result of these experiments (according
to Engelmann) is that, generally speaking, the movements Vs and Vd are the
only ones of which the commencement is clearly traced in the cardiogram.
The beginning of Vs coincides with the beginning of the second rapid rise,
and of Vd with that of the rapid descent from the summit of the curve. By
using the signal, however, it is possible (taking the average of a good number
of experiments) approximately to determine the other periods of the pulsatory
cycle, and to estimate their duration in hundredths of a second. (Engelmann,
" Observations et experiences sur le coeur suspendu," Arch. Neerlandaises. voL
xxvi.)

B. Warm -Blooded Animals. — The methods employed for the graphic
registration of oscillations of pressure and volume of the heart in situ,
were discussed in the chapter. Changes in form may be recorded by the

IX

CARDIAC MUSCLE AND NERVES

291

method of multiple suspension from writing levers, attached by threads to
different parts of the heart (Francois-Franck, Knoll). Various methods have

FIG. 124. — Oehrwall's tonograph. c, Glass bulb to cover outside of heart; 1>, reservoir of
nutrient fluid ; c, tonograph for right auricle ; '/, tonograph for ventricle ; e, /, clips for
altering communication with reservoir.

been adopted in the study of the mammalian heart, independent of any
cerebrospinal nervous influence and of the systemic circulation, with the
object of more or less completely isolating the- cardie-pulmonary circulation

FIG. 125. — Marey's myograph for recording movements of frog's heart in situ. This is a sort of
clip formed of two spoons supported by two curved arms at right angles, one fixed, the other
movable. The latter carries a horizontal lever, provided at the end with a point, writing on
a smoked cylinder. The movable spoon, which is displaced at each systole, is brought back
to its original position at each diastole by a fine rubber thread, fixed by a pin to the board on
which the frog is fastened. Both spoons are connected with wires, by which various kinds of
electrical stimuli can be transmitted to the heart. The exact moment of stimulation is
recorded in the cylinder by a Deprez signal.

(Newell, Martin, H. E. Hering, Hedoii and Arrous, and others). Langendorff
(1895) was the first who succeeded by the method of direct transfusion through
the coronary arteries in keeping the mammalian heart alive for any consider-
able time, when completely isolated and removed from the body (under which

292

PHYSIOLOGY

CHAP.

conditions, without special treatment, it speedily ceases to beat). By means

of a cannula "tied to
the aorta, in the direc-
tion of the heart, he
caused blood or other
nutrient solutions to
circulate at a tempera-
ture of 38° C. under a
pressure corresponding
to the normal pressure
of the aorta. The fluid
keeps the semilunar
valves closed, circulat-
ing through the coron-
ary system of the heart,
and flowing out again
through the opening in
the right auricle. The
cardiac cavity remains
empty. A heart thus
artificially fed is cap-
able of continuing its
activity almost nor-
mally for many hours.
The graphic record of
its movements can be
taken by means of sus-
pension, or (after oc-
cluding the veins of
the right auricle) by a
manometer applied to
the pulmonary artery
(Siewert, 1904).

FIG. 126. — Engelmann's myograph for recording beats of frog's
heart in situ, when suspended from the apex by a thread
connected with a highly sensitive lever. The apparatus is a
two-armed lever, one arm of which is attached to a tine silk
thread, the other to a long straw or strip #f aluminium, which
magnifies the movements of the writing point on a smoked
surface. At the end of the thread is a fine glass hook, with
sharp point, which is inserted into the tip of the apex, after
cutting the fraenum by which the two layers of the pericardium
are united dorsally.

II. The fact that
it impossible to keep
the isolated heart of different animals alive for a comparatively
long period has been used as the start-
ing-point for a series of researches on the
nutritive medium, or external chemical
conditions, necessary to its survival.

This work has familiarised us with
the so-called physiological solutions,
which are artificial nutrient fluids,
capable (at least for a certain time) of
replacing the blood, since they contain a fc
all the elements necessary for sustaining FIG. i27.-cardiograms taken from

., •..[, 0,1 i mi • fr°8 by Engelmanns method, a,

the llle OI the heart. I he importance Commencement of ventricular
f\f fViia anKianf ovr>aarle fV»o lirnifa r»f ^-V»c» systole ( Vs) ; b, commencement of

ol tins subject exceeds the limits 01 uhe diastoieVd);c, curves of a tuning-
present chapter, for it may logically Snjhich vibrates 10 times per
be concluded that artificial fluids which

are capable of sustaining the vitality of the excised heart will
also maintain the vitality of other organs or isolated tissues, or are,

ix CAEDIAC MUSCLE AND NEKVES 293

at any rate, innocuous to the body as a whole, when introduced
into the circulation.

We should, a priori, expect the best effects to result from those
solutions which in their chemical composition most closely
resemble the complex constitution of blood — the natural food of
all the tissues. In practice, however, this is the case only to a
limited extent.

A point much discussed by the various investigators has been
'the importance of oxygen in these physiological solutions. No
one, however, now doubts that it represents an element indis-
pensable to the survival of the heart.

Von Humboldt (1797) was the first to emphasise the vivifying
power of oxygen in the excised heart of the frog. Following his
initiative, Castell (1854) made a systematic series of researches in
the same direction. He found that a frog's heart placed in a moist
chamber at 16-20 E. went on beating for three hours in ordinary
air, for twelve hours in the presence of oxygen, for about one hour
in presence of hydrogen or nitrogen, for a few minutes only in
presence of carbonic acid.

In our own researches on the excised frog's heart (1873), con-
nected with a manometer, and filled with serum of pig or rabbit,
we observed that the frequency and force of the beats augmented
each time the serum already used was reinforced by fresh
oxygenated serum ; the rhythm slowed down and weakened when
the heart was made to float in oil. The vivifying action of
oxygen on the frog's heart was confirmed by Kossbach and King.

Langendorff (1884) experimented with the asphyxiated heart,
and noted that it absorbed oxygen with great rapidity, so that the
blood introduced into it suddenly assumed a venous hue.

Yeo (1885) made the reduction of oxyhaenioglobin by the
frog's heart the subject of a methodical research. He found that
this reduction increased with the work done by the heart. Heffter
and Albanese confirmed the fact that the presence of oxygen is
indispensable to the maintenance of cardiac activity.

The most exact and minute researches on asphyxia and the
revivification of the excised frog's heart are, however, due to
Oehrwall (1893-97). He studied the mode of onset and the
duration of asphyxia in the frog's heart filled with blood or serum,
through which a solution of sodium chloride or of some indifferent
gas was circulated, as well as revival by the substitution of
oxygenated for asphyxiated blood, or by the direct action of air
and oxygen.

The importance of oxygen to the function of the heart in warm-
blooded animals was shown by Fano (1889-90) on the embryonic
chick's heart, isolated on the second or third day of incubation.

A. Porter (1898) succeeded in keeping the isolated mammalian
heart alive for many hours in the presence of blood serum and

294 PHYSIOLOGY CHAP.

oxygen under a pressure of two atmospheres. But the same effects
may be more simply obtained by the artificial circulation through
the coronary system of a physiological solution (to be described
below) saturated with oxygen, or even with air. It is essential in
both cases that the fluid should not stagnate in the vessels.

Eusch (1898) found that the circulation of serum instead of
defibrinated blood necessitated a higher pressure to make it circu-
late with greater velocity, in order to provide the heart with the
quantum of oxygen necessary to its activity.

Other researches on the necessity of oxygen to the survival of
the mammalian heart were instituted by Strecker (1900), and
more particularly by Magnus (1902), who was the first to circulate
gases instead of fluids through the coronary arteries of the isolated
cat's heart. He found, on injecting oxygen, that the heart beat
for about an hour. Its arrest is due to the permeability of the
vessel walls by gas. He saw that when hydrogen was injected in
place of oxygen, the heart continued to beat for about half an
hour, while it stopped after a few minutes when carbonic acid was
injected. The beneficent action of the circulating hydrogen
depends, therefore, upon the elimination of the carbonic acid
developed by the heart during its activity ; but hydrogen is not
sufficient to keep it going for a long time, and the heart ceases to
beat after it has exhausted all the oxygen which it holds in loose
combination.

Winterstein controlled the importance of oxygen by circulating
Einger's solution, charged sometimes with oxygen, sometimes with
nitrogen, through the coronaries of the isolated cat's and rabbit's
heart. He came to the following conclusions : —

(a) The mammalian heart requires external oxygen to main-
tain its activity. Its rhythm alters and it soon comes to a stand-
still, if nitrogen is substituted for oxygen.

(5) If after a definite lapse of time the current of oxygen is
re-established, the heart is able to beat again.

(c) It is possible to reproduce the state of asphyxia repeatedly
in the same heart, and in the above experiments it was observed
that the time necessary for reproducing asphyxial arrest was
shorter than that required for its first incidence.

(d) The immediate condition of asphyxial arrest appears to
consist in the consumption of internal oxygen that takes place

f during cardiac activity.

/ Does the function of free oxygen, as the necessary condition of

/ the rhythmic activity of the heart, consist in the oxidation of the

j muscular biogen which produces the alternate contractions and

expansions of the myocardium, or does it rather lie in the oxidation

of the toxic katabolic products that result from the metabolism of

\ the muscle, transforming them into innocuous substances, readily

\ eliminated ?

ix CARDIAC MUSCLE AND NERVES 295

Arguments in favour of this last hypothesis are not wanting,
but the first must also be admitted as credible, until it is directly
contradicted by experiment.

C. Ludwig (1868) was the first who employed the method of
artificial circulation in excised organs, in studying their survival.
The primitive physiological solution, consisting of a dilute solution
of sodium chloride (0*50-0'75 per cent), was largely used by him
and his school as a substitute for defibrinated blood, in experi-
menting on the metabolism of excised organs. A little serum
added to the saline will keep up the vitality of the excised heart
of a frog for a very long time.

Kronecker and Stirling (1875), however, found that the beats
of a frog's heart tied by the ventricle to a cannula (Bowditch's
preparation) were retarded, and its activity brought to a standstill
in a short time, when a simple 0*6 per cent solution of NaCl was
substituted for the blood or serum. Salt water, therefore, does
not in itself contain the whole of the chemical constituents necessary
for the maintenance of cardiac activity.

Merunovics (1877) tried the effect of watery solutions made of
the ash, or the alcoholic extract of serum, which, he found, main-
tained cardiac activity better than the simple solution of sodium
chloride. He attributed this effect to the beneficial action of the
alkaline carbonate.

Stienon (1878), following Merunovics, observed that the
difference between the action of the fresh serum and its filtrate,
after this had been boiled, consisted in the more limited capacity
of the latter to revive a cardiac preparation of which the activity
had been reduced to its minimum by prolonged treatment with
saline. He also found that neutralisation of the normal alkalinity
of the serum with acid diminished its beneficial action on the
heart. Lastly, he demonstrated that a solution of sodium chloride
rendered alkaline with O'l per cent sodium carbonate is capable of
restoring the activity of a heart that had previously been arrested
by treatment with salt solution. Gaule, later on, found it more
useful for this purpose to add a small quantity of soda instead of
the carbonate, pointing out that the alkali is neutralised during
cardiac activity by the development of carbonic acid, which converts
it into the carbonate.

Martius (1882) explained the beneficial action of serum by
assigning a greater importance to its organic than to its inorganic
constituents, and to serum albumin in particular, assuming that
the development of cardiac energy was dependent on the presence
of some nutrient matter in the circulating fluid.

Against this positive assumption, however, we must set the
work of Ringer, who made a series of experiments to show that
the addition of calcic or potassic salts to the NaCl solution
effectively prolongs cardiac activity, as has since been confirmed

296 PHYSIOLOGY CHAP.

by all who have taken up this subject. Einger's solution
consists of —

100 c.c. of a 6 per cent solution of NaCl
1 „ 1 „ XaHCO3

„ 1 ,, „ CaCl2

075 „ 1 „ „ KC1

Locke (1895) showed by new work that the addition of a small
quantity of glucose to Einger's solution rendered it more capable
of maintaining cardiac activity.

Gothlin, under Oehrwahl's direction, has recently (1902)
carried out some detailed experiments on the chemical conditions
of cardiac activity in the excised heart of the frog. He prepared
a complex solution of mineral substances, including all those
which chemical analysis has shown to be present in blood serum,
in the following proportions : —

NaCl . . . 0-65 percent. Cl . . . . O'Ol percent.
NaHC03 . . 0-1 „ CaCl2 . . . 0-0065 „

Na2HP04 . . 0-0009 „ XaH2P04 . . 0-0008' „

He found that on replacing the blood by this solution cardiac
activity was maintained unaltered for many hours. The pro-
portions in which the different salts enter into solution are by no
means unimportant. On substituting Einger's solution for the
above, both rhythm and type of beat were modified. Gothlin
further saw, on preparing solutions in which one or other of the
constituents predominated (with the object of determining the
influence* of each upon cardiac activity), that the results indicated
all to be more or less necessary to its maximal prolongation.

In a second series of researches he proposed to determine on
what the great difference between the survival period of a heart
treated with his solution, composed solely of inorganic substances,
'and that of a heart treated with normal blood, depends. As regards
the importance of the erythrocytes and of haemoglobin the fact he
discovered is worth noting, that a haemolytic fluid (i.e. one which
contains dissolved haemoglobin) is injurious rather than beneficial.
He explained the toxic action of this dissolved haemoglobin to
consist in its combining with the lime-salts of the serum, so that
they are removed from the heart, which requires lime salts electro-
lytically dissociated in the form of Ca-ions. In fact, he found that
the subsequent addition of lime salts renders haemolytic blood
innocuous.

In other experiments he found that after weakening the heart
with his saline solution, he could restore its activity by perfusing
it with a new complex solution consisting half of serum of ox
blood, half of the saline solution. He concluded that serum must
contain a substance capable of exerting this beneficial action
on the heart, and proposed to ascertain experimentally which it

ix CAEDIAC MUSCLE AND NERVES 297

was of the numerous organic substances present. He tested
glucose, serin, and paraglobulin with negative results.

Baglioni (1905-6) was more fortunate in his experiments on the
isolated heart of Selachians. He knew from the previous researches
of Stadeler and Frerichs, and of v. Schroder, that the blood of
these animals is very rich in urea dissolved in the plasma.
According to v. Schroder the blood of the Scyllium contains on an
average 2'61 per cent urea. This facts explains the high values
'of the molecular concentration of the blood in these fishes, which
corresponds to a solution of about 3*5 per cent of NaCl. Straub
had already found that a saline solution of this concentration was
incapable of keeping the excised heart of these animals alive, even
for a short time — an observation contrary to what had been
observed on the hearts of frogs and other poikilotherniic animals.
Baglioni discovered that it is possible to keep the isolated Selachian
heart alive for a prolonged period by treating it with a solution
containing a definite amount of urea. He found the most effective
solution to be one that contained 2 grrns. of urea, and 2 grins, of
sodium chloride in 100 c.c. of tap water, which invariably yields
traces of lime salts. He further tried to determine the specific
action of urea, and concluded from his experimental results that it
promotes the contraction of the muscle cells, while larger doses
arrest the heart in systole. Sodium chloride, on the contrary,
promotes expansion of the muscle cells, and large doses cause
diastolic arrest.

Lambert (1905) confirmed the favourable action of urea on the
frog's heart ; Baglioni and Federico (1906) on that of the toad.
In these animals, also, urea increases the intensity and duration of
the systolic phase.

Analogous observations were made on the isolated heart of
warm-blooded animals Gross (1903) carried out a methodical
series of experiments on the action of the various components of
Ringer's solution, confirming the results already obtained for the
frog's heart. The antagonism in the action of potassium and
calcium ions was marked. The former exerted a systolic, the
latter a diastolic action ; in large doses the first arrested the
heart in systole, the second in diastole.

Langendorff and his pupils, confirming the necessity of the
presence of lime salts, studied the action of dissolved haemoglobin,
when they found that only certain mammalian hearts behave like
that of the frog. The hearts of cat and dog do not to any marked
extent exhibit toxic effects with dissolved haemoglobin, while that
of the rabbit behaves like the frog's heart. In explanation of this
difference, Langendorff points out that the rabbit's erythrocytes
contain a much larger quantity of potassium salts than those of the
dog or cat. Supposing that a large amount of potassic salts are
diffused in the rabbit's serum along with the haemoglobin, these

- *

298 PHYSIOLOGY CHAP.

might exert a toxic action upon the cells of the myocardium. The
beneficial effects of adding lime salts to the haemolytic fluid may
be explained by the antagonism between the salts of calcium and
potassium.

Bachmann (1906), under Oehrwall's direction, carried out a
fresh series of researches upon the action on the isolated
mammalian heart of the organic nitrogenous substances present
in normal blood, adding it in known doses to Locke's solution,
and perfusing it by Langendorff's method. He studied the action
of urea, of ammonium carbonate, of sodic hippurate, of sodic
urate, of creatine, of hypoxanthine, of xanthine, of allantoin.
Generally speaking, he found that these substances, in doses
approximately equal to their proportions in normal blood,
exercised only a slight and parallel action upon the heart, in-
creasing the amplitude of the systole. Some of them further
accelerated the frequency of rhythm, in particular urea, which
agrees completely with the results of Baglioni.

Special mention must be made of the recent attempts to
revive the dead heart of warm-blooded animals. Kuliabko
(1901-3) was the first to revive the heart of animals three or four
days after death (the bodies being kept meantime in ice), by
perfusing the coronaries with Einger- Locke solution. Seven
days after death it was found impossible to revive the normal
pulsations of the whole heart ; fibrillary contractions could, how-
ever, be observed in the auricles. The heart of an infant that
had died of pneumonia was made to beat again after twenty hours. J

H. E. Hering continued the researches of Kuliabko on the
hearts of rabbit, cat, and monkey. In a monkey found dead in
the laboratory he succeeded, four and a half hours later, in
reviving the heart, left in situ. The body was then frozen. On
the following day, i.e. 24 hours and 32 minutes after the animal
had been found dead, the heart was revived for the second time.
The carcase was again frozen, and a third revival successfully
attempted 53 hours and 43 minutes after.

The same experiments of revival were attempted on the
human adult heart. Dencke and Adam succeeded in obtaining
pulsations in the heart of a criminal forty-three years old, 13
minutes after his execution.

More recently Hering succeeded, with Einger's solution alone,
in reviving the heart of a young criminal of thirty-five, eleven
hours after death, and was able to use it for experiment for
three hours. It is interesting to note that both Dencke and
Hering assert that they found no difference between the human
and other mammalian hearts as regards their reaction to circulating
fluids.

TT^-The most generally noted and recognised fact is that the
conditions of rhythmical cardiac activity are located in the

IX

CAKDIAC MUSCLE AND NEKVES

299

heart itself, and are independent of the connections which unite
it by the afferent nerves with the cerebrospinal axis. Galen was
aware that the excised heart is able to beat for a considerable
time. Under favourable conditions of moisture, temperature,
irrigation with blood and other nutrient fluids, and in presence
of oxygen, the excised heart, not only of cold-blooded animals but
of mammals also, may continue its functions for many hours.

TheearlierHallerian
'doctrine, which saw in
this fact a proof of the
rhythmic activity of
cardiac muscle inde -
pendent of nerves and
nerve-centres, was dis-
allowed after it had
been shown by Bichat
and J. Mliller that the
peripheral sympathetic
ganglia function as in-
dependent centres in the
organs of vegetative life,
while Eeniak (1844),
Ludwig (1848), and
Bidder(1852)discovered
a nerve-plexus rich in
ganglion cells in the
frog's heart.

Eemak demonstrated
the existence of a con-
spicuous accumulation
of ganglion cells at the
mouth of the sinus
venosus in the right
auricle of the frog's
heart. Ludwig de-
scribed other ganglionic
elements in the region of the interauricular septum. Bidder
discovered two other masses of ganglion cells near the auriculo-
ventricular groove (Fig. 128). Nothing after these discoveries
could be more natural than to ascribe the function of excitatory
centres of the rhythmic peristaltic movements of the heart to
these intracardiac ganglia.

Certain well-known experiments of Stannius(1852) gave fresh
sanction to this theory of the intracardial ganglionic centres,
although they received various and even contradictory interpreta-
tions. In his experiments on the frog's heart Stannius discovered
two facts which appeared to be of extreme interest : — -

FIG. 128. — Interauricular septum of frog's heart. (Bidder.)
a., Muscular fibres ; b, endocardium ; c, free border of
septum ; d, d, ventricular walls ; e, f, right and left
branches of cardiac vagus, with partial decussation ; h, h',
anterior and posterior nerves to septum, with numerous
ganglion cells, particularly at points k, k' ; I, ?', ganglia
near the auriculo-ventriculur border (Bidder's ganglia).

300 PHYSIOLOGY CHAP.

(a) When a ligature is applied at any height of the auricle,
between the opening of the sinus venosus into the right auricle,
and the region nearest the auriculo- ventricular junction, arrest of
the heart is, ipso facto, produced in all parts below the ligature,
while above, in the sinus and the part of the auricle that is not
blocked, the rhythm is undisturbed.

(b) When a second ligature is applied to the auriculo-
ventricular groove in a heart that has been arrested by the first
ligature, the ventricle begins to beat again, even though much
more slowly than the normal, while the auricles still remain
motionless.

Eckhard (1858-60) showed that practically the same results
were obtained by making incisions in the frog's heart, as by the
method of Stannius. At the same time he denied their supposed
constancy, and found a great variety of effect both from ligation
and from sections, in accordance with fluctuations of external
temperature, and the varying sensitivity of the preparation, and
more particularly of the different regions operated on. He
confirmed the fact already observed by Heidenhain that the
arrest of the heart produced by the ligature or section is not
permanent, for the beats invariably recommence after a longer or
shorter pause (lasting from a few minutes to an hour).

None of the several hypotheses advanced in explanation of
these facts will bear searching criticism. Eckhard accounts for
the effect of the first Stannius ligature on the rhythm of the
heart by assuming a sort of nceud vital, represented by Kemak's
ganglia. To explain the effects of the second ligature, he assumes
that it provokes a certain excitation of Bidder's ganglia. Eemak's
ganglia must function automatically, since the spontaneous move-
ments of the heart cease when their influence is cut out ; Bidder's
ganglia must be reflex in function, since the stimulus of ligaturing
the auriculo-ventricular junction is required to throw them into
activity. When, in fact, instead of ligation, an incision is made
in this region, which would not have much excitatory effect on
Bidder's ganglia, permanent standstill of the ventricle, usually
preceded by only 8-10 beats, is produced.

This theory, which involves a specific differentiation of the
cardiac ganglia into automatic and reflex, is unsatisfactory. In
order to defend it, we must assume that the upper Stannius
ligature has, for its sole effect, the physiological exclusion of
Kemak's automatic ganglia, and that the lower ligature on the
contrary causes the reflex excitation of Bidder's ganglia.

We attacked this question in Ludwig's laboratory in 1872, and
saw that when the ligature was applied to the frog's heart, after
the insertion of a simple cannula, with its point projecting into
the ventricle, the same effects were obtained as with the Stannius
ligatures. But when the cannula was filled with fresh rabbit's or

IX

CAEDIAC MUSCLE AND NEKVES

301

sheep's serum, by which a certain pressure was exerted on the in-
terior of the frog's heart, it began to beat again vigorously, regardless
of the point at which the ligature was applied. In order to study
the course of the heart's action under these conditions we connected

FIG. 129. — Paroxysm in form of ascending staircase, shown by frog's heart, filled with sheep's
serum, and tied at auriculo-ventricular groove, immediatefy after attachment to tonographic
apparatus. (Luciani.)

the cannula with the excised frog's heart to a small recording
mercury manometer (Fig. 121), and then obtained the curves of
three distinct and quite characteristic phenomena, representing

FIG. 130. — Tetaniform paroxysm presented by frog's heart already attached to tonographic
apparatus, as the effect of a second ligatm-e 2 mm. below the auriculo-ventricular groove.
(Luciani.)

three different phases of cardiac activity, which precede the
exhaustion of the heart.

The first phenomenon may be termed the " paroxysm "

FIG. 131. — Tetaniform paroxysm commencing at «, after ligature of auricles, converted at'fr into
an ascending staircase, by the momentary opening of the valve of the tonographic apparatus.
(Luciani.)

(accesso), and consists in a sudden increase of cardiac muscular
tonus in conjunction with great frequency of beat. With
the progressive diminution of tone the beats become less
frequent, but are at the same time more ample in diastole,
since the presystolic filling of the ventricle steadily increases.

302

PHYSIOLOGY

CHAP.

This fact is shown (owing to the special character of the apparatus)
in the curve of Fig. 129 as an ascending staircase, produced by the
progressive increase not of systole, but of diastole, in proportion
as the tone of the myocardium diminishes. For when a second
ligature is applied to the auricles, the heart being already connected
with the recording apparatus, the tracing assumes a tetanic form,
and the beats, as they become more excursive, rise above a regularly
descending line, which is the exact expression of the progressive

Fir;. ISSL—Tetaniform paroxysm commencing at a after provisory ligature of auricles ; converted
at b into slightly ascending staircase, the beats becoming less frequent, after removal of
ligature. (Luciani.)

decrease in tonicity (Fig. 130). If, after applying the second
ligature to the auricle, the valve which separates the heart from
the vessel of serum is opened, the beats which accompany the
attack assume the form of an ascending staircase, as in Fig. 129,
which bears out our interpretation (Fig. 131). Practically the
same result is obtained if the ligature is applied soon after the
paroxysm has commenced (Fig. 132).

F;G. 133.— Periodic rhythm shown by frog's heart tied at the auricles, 2 nun. above the
auriculo-ventricular groove, tilled with rabbit's serum and attached to tonographic apparatus
of Fig. 121. (Luciani.) The figure shows four periods of regular increase, both in number of
beats in groups and in duration of pause. The divisions along the abscissa represent
intervals of 1 second.

The phenomenon of "paroxysm," which shows that the
ligature applied at different heights of the auricles (in conjunction
with the action of serum and of a certain degree of pressure)
invariably acts not merely by separating, but also by contusing
and irritating the walls of the heart, seems to us the most direct
refutation of the doctrine of the twofold nature of the cardiac
ganglia.

When the paroxysm is over, a new phenomenon appears which
we have termed periodic rhythm, in which the cardiac pulsations

IX

CAEDIAC MUSCLE AND NEEVES

303

occur, not at regular intervals, but in groups, separated by long
pauses (Fig. 133). This strange effect may continue for two or
three hours, and usually exhibits a regular course. Often the
duration both of the groups and of the succeeding pauses declines
regularly; at other times it increases in the primary phase, and
declines in the next : other cases again present irregular oscillations
with a constant tendency to decrease.

The number of beats in each group has no apparent relation
with the duration of the respective pauses. Their frequency varies
usually in regular order.

The more typical groups commence with rare contractions that
are gradually accelerated, and then again slow down into a long
pause. The height of the contractions in each group usually

FIG. 134. — Three groups of beats obtained from various frogs' hearts tied at the auricles.
(Luciani.) In A the beats form a descending staircase ; in B they are approximately the same
height ; in C the first four beats form aii ascending staircase.

forms a descending staircase ; more rarely a straight horizontal
line ; more rarely still, a slightly ascending staircase (Fig. 134).

Our experiments tend to show that the groups are of longer
duration, and the intervals between them shorter, when the
ligature is nearer the sinus. This fact agrees with Eckhard's
conclusions — to the effect that the duration of the pause increases
in proportion as the incisions in the heart are made at different
heights, from limit of sinus to auriculo-ventricular groove.

The periodic rhythm is an absolutely constant phenomenon
when the cannula is attached at any height whatever of the
auricles, and given all the other conditions of our method, in re
serum, temperature, and pressure. When the ligature falls on the
auriculo-ventricular groove, the phenomenon may appear in a
rudimentary form, or may be altogether absent. When it falls on
the upper limit of the ventricle (1-1 '5 mm. below the auriculo-
ventricular groove) Bowditch's preparation is obtained, of which we

304 PHYSIOLOGY CHAP.

shall speak below. When the paroxysm is over there will in every
case be some isolated contractions, after which all spontaneous
movement ceases, although the ventricle preserves its reflex'
excitability, and responds to electrical and mechanical stimuli by
strong contractions. When the ligature falls on the junction of
the sinus, the periodic grouping of the cardiac contractions is
barely and irregularly indicated. When, lastly, it falls on the sinus
(1-1-5 mm. above its opening into the right auricle) no trace of
periodic grouping is visible.

These facts obviously exclude the hypothesis that the periodic
rhythm observed by us during the above experimental conditions
depends exclusively on a specific toxic action of the serum, or on
asphyxia, due to its non- renewal, as was held by Rossbach
Langendorff and others ; while they show us just as convincingly,
that in the case of our experiments the fundamental determining
condition of the phenomenon consists in the physiological exclusion
of the sinus venosus effected by the ligature.

They further show that the rhythmical activity of the heart is

LHUILULUIL

FIG. 135. — Crisis of periodic rhythm in frog's heart itied 3 mm. above the auriculo- ventricular
groove, and filled with pig's serum. (Luciani.) Shows gradual dissolution' of groups into
isolated beats.

most highly developed in the venae cavae and sinus venosus
(where lie the conspicuous ganglionic masses described by Eemak),
after the separation of which the rhythmical impulses probably
encounter resistance, and must summate before they can be
efficacious. Accordingly, there are long pauses, during which
tension is accumulated, and groups of contractions, during which
it is discharged again.

In proportion as the activity of the heart exhausts itself the
pauses shorten, and the beats in the groups are separated by wider
intervals, till eventually all periodic grouping disappears. This is
the phenomenon we have termed the " crisis " (crisi), represented
by a longer or shorter series of single beats, which become con-
stantly rarer and weaker, until they disappear entirely, as soon as
the asphyxia and exhaustion of the heart are complete (Fig. 135).

The crisis indicates that the resistances which determine the
periodic rhythm are gradually diminishing, and that the heart is
slowly adapting itself to the new conditions produced by the
ligature. Eenewal of the serum after the crisis has set in does
not reinstate the periodic rhythm. This is a striking fact, and in
our opinion indicates that the adaptation has been complete.

IV. At the time at which we took up these physiological

ix CAKDIAC MUSCLE AND NEEVES 305

studies of the frog's heart there was a great tendency to deny any
kind of automaticity, and to regard cardiac rhythm as a simple
reflex phenomenon dependent on rhythmic excitation determined
by external stimuli. Goltz assumed that systole, by removing the
cardiac stimulus (due to the blood and its gases), induced diastole.
But this hypothesis disregards the elementary consideration that
the excised heart, in which rhythmical filling and emptying is no
longer possible, continues to beat vigorously.

. Others ascribe a kind of elastic resistance to the heart, alternat-
ing with the different phases of its activity. The stimuli, as
continuous agents, must develop a certain tension in order to
surmount this elastic resistance, before they can produce their
effect. When systole is over, resistance rises, and a new discharge
can only take place after the latent excitation has overcome the
corresponding tension. This schematic representation implies a
tacit recognition that the immediate cause of rhythmical activity
is a condition intrinsic to the organ. But the naivett of this
hypothesis, which predicated a kind of elastic resistance, was shown
on the discovery of periodic rhythm, which, in its multiple
manifestations, its varied course, and its crisis, shows how change-
able the internal conditions which determine the activity of the
heart may be, when the external conditions remain constant and
almost unaltered. " The rhythm of the heart-beats " (as we concluded
in 1873) " is the external expression of a corresponding rhythm of
the nutritive process which is accomplished within the organ."

Henceforward, no one contested the theory of the automaticity
of cardiac action, since it was impossible to invent a hypothesis
which explained the many and complex forms of its rhythm by
any external stimulus.

The automatic excitability of the heart does not of course
exclude its reflex excitability, and the doctrine of Bidder and
Eckhard, who assumed the existence of distinct automatic and
reflex mechanisms, must be modified to the effect that the different
parts of the heart exhibit different degrees of excitability, whether
automatic or reflex.

It can be asserted on the ground of weighty arguments that
automatic excitability is most pronounced in the venae cavae and
sinus, less in the auricles, and least in the ventricle. The facts
already cited showing that (i.) the duration of cardiac arrest, after
applying ligatures or sections to the heart by the methods of Stannius
and Eckhard, becomes increasingly greater, the lower these are
placed on the auricles between the orifice of the sinus and the
auriculo- ventricular groove ; (ii.) the periodic groups become con-
stantly smaller and the pauses longer with physiological separation,
as in our method, combined with the action of serum and of
pressure ; (iii.) the arrest of cardiac activity by exhaustion due to
whatever means, which takes place in different parts of the organ

VOL. i x

306 PHYSIOLOGY CHAP.

at different times, i.e. first in the ventricle, then in the auricles,
lastly in the sinus and the venae cavae, — all go to prove that
automaticity in the various parts of the heart decreases gradually •'
from sinus to auricles, from auricles to ventricle. To these facts,
as determined on the heart of the frog, we may add those observed
by Mac William on the fish's heart. When it is divided into
segments each of these continues to beat, but each with its own
proper rhythm — the more slowly in proportion as the segment is
farther away from the veins opening into the auricles.

In mammals, again, similar phenomena may be observed. By
an ingenious operative method Tigerstedt succeeded in the rabbit
in completely separating the auricles from the ventricles without
interrupting the circulation, and found that the latter continued
to beat, although the rhythm was markedly slower.

Porter, on extending the experiments with artificial perfusion
through the coronary system, found that the rhythm persisted even
in isolated sections of the ventricles connected with the rest of
the heart by a single branch of the coronary artery.

It may therefore, generally speaking, be concluded that every

'- segment of the heart, whether in poikilothermic or in homothermic

I'1 animals, is endowed with rhythmical automatic excitability, which

decreases from the sinus venosus downwards, from the mouths of

the venae cavae to the auricles, from the auricles to the ventricles,

Other experiments show that the rhythmical activity of the
»| more automatic determines the rhythm of the less automatic
' segments. Gaskell found that changes of temperature localised at
the sinus in the frog's heart modified the frequency of the beats of
the whole heart, as if the heart had been warmed or cooled in toto.
Adam experimented by the same method on the heart of cat and
rabbit. He saw that when an area between the mouth of the two
venae cavae near the lowest segment of the wall of the right
auricle was warmed or cooled, the frequency of the beats of the
whole heart was modified. No effect was produced on varying
the temperature of the venae cavae or pulmonary veins, of the
two auricular appendages, or the walls of the left auricle. It is,
'/ therefore, evident that the sinus venosus in cold-blooded animals
and the orifice of the venae cavae as indicated by Adam on the
mammalian heart, represent the most automatic parts, in which
the pulsatory cycle is initiated, and on which the frequency of
rhythm of the entire heart depends.

When automatic excitability is played out, reflex excitability
usually persists for some time ; when the heart is stimulated either
by a localised mechanical shock or by an induction shock, it reacts
with a beat or a series of beats, which are either transmitted to the
other segments of the heart, or remain circumscribed in the
segment stimulated.

When reflex excitability is extinguished, the reaction to

ix CAEDIAC MUSCLE AND BEEVES 307

external stimuli ceases in the various segments, in the same order
in which the automatic excitability disappeared ; first, the ventricle
becomes inexci table, next the auricles, and shortly after the sinus
venosus. On the basis of these facts it may be sustained that the
two forms of excitability are in direct reciprocal relation, and that
the segments most excitable to internal stimuli are also the most
excitable to external stimuli.

JVL_ Does the falling excitability (automatic and reflex) from
sinus venosus (or mouth of venae cavae) to auricles, from auricles
to ventricles, which determines cardiac rhythm, depend on the
varying number and arrangement of the ganglion cells in the
different segments of the heart, since these have the property of
generating rhythmical impulses which are then transmitted to the
muscle cells, provoking contraction in the form of a peristaltic wave ;
or is it independent of the intracardiac nervous elements, and
inherent in the muscle cells of the myocardium ? For a long time
the first doctrine was very generally admitted. Two special
phenomena were adduced in its support which from their simplicity
appeared to be direct evidence : —

(a) The lower two-thirds of the apex of the frog's ventricle,

n which shows no nerve-cells under the microscope, invariably ceases

j\to beat automatically when separated by an incision or ligature

j tfrom the other parts of the heart, which are provided with nerve

elements (Stannard, Eckhard and others). *•

(&) Circumscribed excitation of any part of the frog's heart and
its integuments always produces a contraction that commences in
the_auricles, and not at the point directly stimulated (Kiirschner,
Budge, Pagliani).

The first phenomenon seemed to be a direct proof of the
neurogenic origin of automatic excitability, and the second a direct
proof of the neurogenic origin of reflex excitability. Subsequently,
however, the supposed constancy and affirmative character of both
was disputed.

Eanvier and Engelmann observed rhythmical pulsations under
the microscope in fragments of the adult heart in which it was
impossible to detect any trace of nervous elements. The apex of
the ventricle, again, when excised and lightly attached to a
cannula will, after a pause (if conveniently distended and irrigated
with a nutrient fluid), begin to beat spontaneously, and continue to
do so for a long time, although the rhythm may be slower than
usual. This proves that even if this part has no ganglia, it also
has an inherent automatic capacity, although to a much smaller
extent than the rest of the heart. It should be added that this
masked excitability is a characteristic peculiar to the ventricle of
the adult frog. That of the tortoise, on the contrary, although it
has no nerve-cells, will beat for a considerable time after it has
been isolated (Gaskell).

308

PHYSIOLOGY

CHAP.

J

Some trustworthy observers, on the other hand, have con-
tradicted the statements of Kiirschner, Budge, and Pagliani, and
hold that the reaction of the heart to a circumscribed stimulus
invariably commences in the part directly excited, whence it is
propagated either in the peristaltic or in the anti-peristaltic form,
i.e. from auricles to ventricle, or from ventricle to auricles.

On the theory of the myogenic origin of the rhythmic activity
of the heart in all animals, both in the embryonic and the adult
state, this rhythmicity must be an inherent property of the muscle
cells, independent of the agency of the nervous system (whether
extra- or in tra- cardiac), which thus fulfils simply a secondary
function, regulatory and trophic. Many workers have contributed
to the elaboration and stability of this view, among them
Engelmann in Germany (1893-97), Gaskell in England (1882-87),
and Fano in Italy (1885-90).

Some of the experimental arguments on which the myogenic
hypothesis was founded have been disproved by more recent
investigations carried out with better technical methods, which
show the presence of nerve-cells in points of the heart at which
their non-existence had previously appeared certain. The follow-
ing arguments of the myogenists, however, seem incontestable : —

(a) The automatic movements of the embryonic heart begin
before the presence of ganglion cells can be demonstrated under
the microscope. In the chick, for instance, the heart begins to
beat thirty-six hours after incubation, while the ganglion cells are
only, formed after six days (His, jun.) ; the human heart begins to
beat three weeks after gestation (Pfliiger), while the nervous
elements only appear at the commencement of the fifth week (His,
jun.). The ganglia or cardiac nerves are not formed in situ by the
differentiation of the muscle cells of which the cardiac tube is
composed, but enter the heart from outside, from the cerebrospinal
and sympathetic systems, penetrating along the veins in the lower
vertebrates (fishes, frogs), along the arteries in the higher verte-
brates (birds, mammals) — (His and Eomberg).

(&) In studying the cardiac function of the excised embryonic
heart of the chick on the second or third day of development, Fano
succeeded by the photographic registration of its movements in
demonstrating that the beats of the primitive cardiac tube differ in
no essentials from those of the adult heart. It exhibits a rhythm
in the form of a peristaltic movement that passes from the auricular
to the ventricular segment of the tube. The first portion is more
resistant, the second is more easily exhausted. If divided by a
transverse section, the first continues to beat, the second stops.
Longitudinal or oblique sections of the cardiac tube show that the
segment nearest the venous end is the first to contract, and from
it the contractile wave is propagated towards the arterial
extremity. Toxic or indifferent gases first arrest the beats of

IX

CARDIAC MUSCLE AND NEKVES

309

the ventricular, then those of the auricular portion. On sub-
stituting air or oxygen for the said gases, shortly after the beats
have been arrested, they are seen to reappear, first in the auricular,
subsequently in the ventricular section. In short, the embryonic
heart of the chick, which has no nerve elements, exhibits like the
adult heart a decrease of automaticity from the venous to the
arterial end (Fig. 136).

(c) No less interesting are the observations of Fano in regard
to the mode in which the rhythm-
ical automatic activity of the

same embryonic heart becomes
exhausted. When isolated and
exposed to favourable conditions
of moisture and temperature, it
continues to beat for a time which
usually exceeds one hour, and
may reach a maximum of two or
three. But in the last stage o
its life, rhythmical is transformed
into periodic activity, as repre-
sented by groups of beats separated
by long pauses, in complete agree-
ment with the phenomenon dis-
covered by us on the adult heart
of the frog. As in that, so in
the embryonic heart, the periodic
rhythm gradually resolves itself
into an irregular series of single
beats, which become constantly
weaker and less frequent until
they vanish altogether. The
auricular or venous segment of
the heart not only beats a good
deal longer than the ventricular
segment, but it exhibits the
periodic grouping of beats much
later. After the automatic rhythm
ceases, reflex excitability continues for some time. Since these
effects appear in a part entirely devoid of nervous elements, they
can only be due to automatic or reflex excitability of the embryonic
muscle cells.

(d) On repeating the same observations and experiments on
the chick's heart in the second half of its development, i.e. on the
eleventh day of incubation, when there is no essential morphological
difference between it and the adult heart of vertebrates, Bottazzi
obtained the same results as those recorded by Fano for the first
hours of incubation. In that stage of development also automaticity

FIG. l:U5.— Chick's heart on third day of in-
cubation. (Fano.) AD, venous extremity,
from which the auricles develop ; EC,
arterial end, from which the bulbi arteriosi
develop ; EF, median line of ventricular
portion ; AB, concave line, or lesser curva-
ture of heart ; DFC, convex line, or greater
curvature of heart. Each of the divisions
indicated below the figure corresponds to
0'05 mm., and the whole line to 1 mm.

310 PHYSIOLOGY CHAP.

declines from sinus to auricles, from auricles to ventricles.
Functional exhaustion is again preceded by the phenomenon of
periodic rhythm, or crisis, similar to that described by us for the '
adult frog's heart.

(e) We have seen that it is possible to revive the rabbit's heart
five days after death, by the artificial circulation through the
coronary arteries of suitable nutrient fluids, at a given temperature
and pressure (Kuliabko). Now it has been found by experiments
on the vitality of the peripheral ganglionic elements in general,
that they survive suppression of circulation very imperfectly in
comparison with the conducting nerve fibres, and more particularly
with the muscle cells. Langendorff demonstrated loss of excitability
in the ciliary ganglion immediately after bleeding and death from
asphyxia of an animal, and showed that the pre-ganglionic fibres
ceased to influence the pupil long before the post-ganglionic. H.
E. Hering confirmed this fact (1903), but noted that the excitability
of the vagus, and still more of the sympathetic, for the heart, per-
sisted for a considerable time "after the death of the animal. He
further observed that when the cells of the superior cervical
ganglion had ceased to function it was impossible to revive it
by pel-fusion with Ringer's solution, which, however, can restore
vagus excitability six hours after the death of the animal, and
that of the accelerator fibres after a much longer period (fifty-
three hours). If, now, the intracardiac behave like the other
sympathetic ganglia, it is evident that the rhythm of the heart,
which may be re-established by Ringer's solution as much as six
days after death, cannot be due to the ganglia, but must derive
from the automatic recovery of the muscle cells.

The absolute and unconditional value of some of the arguments
for the myogenic theory of cardiac rhythm is challenged by the work
of Bethe (1903), who adopted an improved technique, based on the
staining of nerve elements by methylene blue. According to these
observations thexe_js jiot in the whole body of the frog ajmuscle
richer in nerve fibres than the heart. A fine network of fibrils
, from the minutest ganglion cells invests the muscular sheath of the
entire myocardium, including the apex of the ventricle. Bethe
asserts that the muscles of the auricle in the frog are completely
separated from those of the ventricle, just as these last are
separated from the muscles of the aortic bulb. The nervous
reticulum of the auricles again does not seem to be in direct
continuation with that of the ventricle, but is connected with it
exclusively, or at least to a great extent, by means of Bidder's
ganglia, which, as we have seen, lie in the auriculo-ventricular
groove.

On these histological grounds, Bethe ranges himself among the
supporters of the neurogenic theory, alleging that while the nervous
reticulum of the heart is not the sole incentive to its rhythmic

ix CAEDIAC MUSCLE AND NERVES 311

automatic! ty, it does represent the conducting element of
excitation.

The most important and convincing arguments in favour of
the neurogenic theory of cardiac rhythm were, however, adduced
by Carlson (1904-5).

He directed all his observations to the invertebrate heart, in
which, from the phylogenetic point of view, the automatic activity
of the muscle cells should reach their highest development.

One of the strongest arguments adduced by Engelmann in
favour of the myogenic theory, was the non-existence of nerves
and ganglion cells in the adult heart of many of the Invertebrata
(molluscs, arthropods, tunicates, lower crustaceans). He reasoned
from the observations of A. Brandt, C. Eckhard, M. Foster and
Dew Smith, W. Biedermann and Ransom. Carlson, however,
noticed that these negative results do not hold for all invertebrates.
In a great many molluscs and arthropods the heart is visibly
invested with nerve-cells and fibres, while, according to Hunter,

FIG. 137.— Heart and cardiac nerves of Limulus polypJiemus. "(Carlson.) an, Anterior arteries ; la,
lateral arteries ; In, lateral nerves ; mnc, median ganglionic chain ; os, ostii or afferent
stomata, each pair of which corresponds to one of the segments into which the Limulus heart
is divided.

these elements also exist in certain tunicates, e.g. in Molgula.
Carlson worked on the heart of an invertebrate, Limulus
polyphemus (an arachnid, according to others a crustacean), the
American " horse-shoe crab." The heart of this animal (which in
the best-developed specimens may be as much as 10-15 cm. long)
is in the form of an elongated sac, divided into segments by
arterial rami which originate in a double lateral series (Fig. 137).
During systole this heart contracts simultaneously in its entire
length, or else the wave of contraction is peristaltically propagated
with such velocity that the eye is incapable of following its pro-
gression. The nerve plexus by which the heart is invested is
disposed above the ectocardium in three principal trunks, the
median of which may be regarded as an extended nervous ganglion,
mixed with nerve fibres, while the two lateral nerves, and the
branches by which these are connected with the median ganglion,
contain no nerve fibres. In this case, therefore, it is comparatively
easy to separate the nervous elements without injuring the
muscular walls of the heart, which is impossible in any other
animal.

By a technique as simple as it is conclusive, Carlson has

312 PHYSIOLOGY CHAP.

shown that the conduction of excitability and co-ordination of the
cardiac movements of Limulus depend on the median ganglion
cord. When this is removed the beats cease entirely, while the
intact heart, when exposed, may continue to beat regularly for
many hours. On dividing the cord at any point, the beats become
a-synchronous in the several segments, and continue so for an
indefinite time. When, on the other hand, the muscle is divided
transversely at any point along the heart, while the ganglion cord
is spared, there is no longer any appreciable disturbance of co-
ordination in the pulsations. If a single node of the ganglion
cord is extirpated, the heart ceases to beat in the corresponding
muscular segment, while it continues to beat in the rest.

The ganglion cord of Limulus is the centre not only for the
automatic activity of the heart, but for its reflex activity as well.
It receives the moderator and accelerator nerves, which modify the
cardiac beats acting not directly on the muscle cells, but reflexly or
through the ganglion. When this has been excised, and the beats
of the heart have ceased, rhythmical activity is not restored on
exciting the lateral nerves; tetanic contractions are, however,
obtained.

Lastly, certain cardiac poisons (atropine, nicotine) act on the
Limulus heart as on that of vertebrates, paralysing the activity of
the inhibitory nerve fibres which reach it from without.

There can be no doubt as to the accuracy of Carlson's experi-
ments, or the theoretical conclusions which result from them. As
the supporters of the myogenic theory emphasise particularly the
automatic rhythmical activity of the embryonic heart and that of
certain invertebrates in which nervous elements are wanting ; so
the supporters of the neurogenic theory may invoke the Limulus
heart as direct evidence and proof that its automatic and reflex
excitability, the conduction and the co-ordination of excitations,
depend exclusively on the ganglion cells which it contains.

Without venturing on any general conclusion, and assuming
that the results obtained from Limulus are applicable to the heart
of vertebrates also, it is only fair to admit unhesitatingly that the
neurogenic theory seems more probable since Carlson's discovery
than the myogenic. Its definite and unconditional acceptance for
the heart of every animal could only be possible if, with better
methods of research, it were discovered that both the embryonic
heart of mammals, and the heart of all invertebrates, possess
ganglionic elements that have so far evaded detection.

VL^The elements which constitute the vertebrate myocar-
dium are^otTperfectly comparable with those of either striated
or smooth muscle. They are neither composed of fibres, nor of
fusiform fibro-cells; but consist of nucleated cells of prismatic
form, which usually bifurcate into two broad short processes, and
exhibit a rather dark stria tion. Each cell is joined at its

IX

CAKDIAC MUSCLE AND NERVES

313

extremity to other similar cells by means of little protoplasmic
bridges (Przewoski), and a series of such cells constitutes a cardiac
fibre, which never has a sarcolernma, and is joined by the processes,
as above, to other adjacent fibres, making with them a kind of
network. At certain points, more particularly beneath the
endocardium, are muscle cells that are non-striated, or striated
only in the outer layers, with no striae at the nucleus (Purkinje).
These represent cells which are less well developed and more
embryonic in char-
acter (Fig. 138).

Given this struc-
ture of the ele-
ments of the myo-
cardium, it is easy
on the myogenic
theory to see how
the contraction
wave which arises in
the more automatic
muscle cells of the
venae cavae and
sinus venosus must
be propagated in a
peristaltic form
from cell to cell, in-
dependent . of the
nervous system.
Each cell being in
simple protoplasmic
continuity with all
the rest, the entire
myocardium may,
from a physiological
point of view, be
regarded as a united
mass of hollow muscle. We must now briefly enumerate the
most important experimental facts by which this theory is
supported.

As early as 1874 A. Fick showed that any excitation due to
stimulation of a circumscribed area of the cardiac muscular mass
was propagated in every direction. Engelmann almost simul-
taneously confirmed this fact, and further showed that the con-
traction can be propagated in a ventricle divided into zigzags by
incisions, from one section to another.

Porter (1899) established a similar fact for the heart of
mammals, irrigated with defibrinated blood circulated through the
coronary arteries, at 36° C. After cutting across the mass of the.

FIG. 138. — Muscular network of normal heart of adult man. (Prze-
woski.) 'a, Terminal granular layer; b, filiform protoplasmic
processes, stretched between the muscle cells ; c, nuclei of these
cells ; d, bundle of primitive muscle fibrils.

314 PHYSIOLOGY CHAP.

ventricle, in such a way that the segments above and below were
united only by means of little muscular bridges and the rami of
the coronaries, synchronous contractions were found to persist
throughout the ventricular mass. These facts, which appeared
incompatible with nervous conduction, have, since Bethe's work
on the neuro-ganglionic system diffused throughout the frog's
myocardium, and that of Berkley on the mammalian myocardium,
lost all evidential value, since they can be explained by the
conduction of excitation through the fibrillary nervous network.

Gaskell, to exclude the intervention of nerves and ganglia
in the transmission of cardiac excitation, divided on the tortoise
the large nerve trunks that supply the ventricle, and on the frog
excised the interauricular septum with all its nerve trunks, and
found that the peristaltic propagation of beats from auricle to
ventricle was not interrupted. Analogous experiments with the
same results were carried out at a later time on the mammalian
heart by Krehl, in collaboration with Kornberg. These experi-
ments, however, cannot be adduced in favour of the theory of
myogenic conduction, since it has been demonstrated by the
latest histological methods that the whole myocardium is pervaded
by minute ganglionic elements and nerve fibrils.

Either on the hypothesis of rnyogenic, or on that of neurogenic
conduction, it is difficult to explain the fact of the brief arrests
or delayed transmission of the contraction wave at the points at
which it passes from one segment to the other of the heart, i.e. at
the junction between the sinus and the auricles, the auricles and
ventricle, the ventricle and the arterial bulb.

It was formerly assumed, on the strength of the early
anatomical researches, that each of these parts of the heart
possessed a perfectly distinct system of muscle fibres. For the
heart of man and other mammals, in particular, Bonders admitted
as a well-established fact that there was complete interruption
of the muscular walls corresponding with the auriculo-ventricular
groove, and he used this to account, on the neurogenic theory, for
the perfect a-synchronism between the systole of the auricles and
that of the ventricles. More recent and exact observations have
proved the existence of muscle bridges, which connect the different
parts of the heart, and form a united myocardium.

As early as the end of 1876 Paladinb, in the heart of man and
various other vertebrates, demonstrated the presence of muscular
fasciculi extending uninterruptedly from auricles to ventricles. In
1883, Gaskell demonstrated the same for the hearts of frog and
tortoise, and these observations were subsequently confirmed by
Stanley- Kent (1892-94), by His, jun., and by Engelmann, for the
heart of other vertebrates also.

According to the recent and very minute researches of Tawara
(1905) on the human heart, this connecting system of auriculo-

ix CARDIAC MUSCLE AND NERVES 315

ventricular fibres forms a diffuse and complex muscular ramifica-
tion, which continues uninterruptedly from auricles to ventricles.
From this system a short bundle of muscle goes out at the back to
the coronary sinus, where it joins the ordinary muscles of the
auricle. Another bundle runs inwards from the muscular system,
towards the muscles of the ventricle, and bifurcates at the two
walls of the septum. At the base these two branches break up
into a number of small bundles, some of which enter the musculi
•papillari, while others spread over the whole internal surface of
the endocardium, passing either to the apex or the base of the
ventricles. Throughout its course the auriculo-ventricular bundle
is separated by connective tissues from the cardiac muscle proper,
and connects with the fibres of the ventricle by its terminal
branches only.

It would be interesting to study the effects on cardiac rhythm
of interrupting the
conduction of ex-
citation along this
system of muscle
fibres, which passes
uninterruptedly
from auricles to
ventricles. Some
physiologists have

tne 6X- isolated dog's heart. At I a thread was tied round the bundle of

OT1 the ^s> al^er which a decided allorhythmia of the two cardiac seg-

. . ments is apparent. (Humblet.)

isolated surviving

heart of mammalia : e.g. His, jun., Graupuer, Erlanger, and especially
H. E. Hering. Gentle compression of the principal bundles increases
the interval between presystole and systole, without altering their
normal sequence. Stronger compression produces the allorhythmia,
in which 2, 3, or 4 presystoles correspond with a single systole
(Fig. 139). Marked and sudden compression when the cardiac /
rhythm is very frequent and intense may produce a longer or •*
shorter arrest in systole, after which the ventricles begin to beat
with a rhythm of their own, independent of that of the auricles.
TKe same results occur when the conductivity of the auriculo-
ventricular bundle is impaired by cooling, while the excitability
of the auricles is simultaneously raised by warming.

The experiments which most definitely bring out the im-
portance of this bundle as the bridge across which the wave of
contraction passes from auricles to ventricles, are those of H. E.
Hering (1905) on the dog's heart. He kills the animal, and
then revives the heart (without isolating it from the body),
perfusing Ringer's physiological solution from the aorta through
the coronaries. While the heart is still motionless, he divides the
auriculo-ventricular bundle by a comparatively small incision in

1

Fin. 139.— Tracing of beats of auricle (A) and ventricle (H) of small.
attempted tne eX-

316 PHYSIOLOGY CHAP.

the septum (across the right auricle). Each time the incision into
the bundle of His is complete (as can subsequently be ascertained
anatomically) a sharp functional dissociation between the beats of
the auricles and those of the ventricles, a true allorhythmia,
appears when the cardiac cycle recommences. Hering studied this
effect on ten dogs' hearts, with results as follows : —

(a) The ventricles beat more slowly than the auricles (Fig. 140).

(b) The wave of contraction is neither transmitted from the
auricles to the ventricles, nor vice versa, whether it be spontaneous,
or determined by external artificial stimuli.

• (c) Both auricles and ventricles possess independent automatic
activity.

From these experimental data Hering deduces a new argument
in favour of myogenic conduction, adopting the ideas previously

FIG. 140. — Tracing of beats of auricle (A) and ventricle (V) in a dog's heart, in which
the bundle of His had been cut. Time in seconds. (H. E. Hering.)

brought forward by Gaskell in connection with the amphibian
heart.

According to Gaskell, communicating fibres between the sinus
and auricles, and the auricles and ventricle, present certain
morphological peculiarities in which they approximate to embryonic
cardiac fibres. These less differentiated fibres, which in arrange-
ment and structure resemble those of the primitive cardiac sheath,
have also from the physiological point of view preserved a more
embryonic character, since they are endowed with a far higher
degree of automatism, and probably (according to Gaskell) conduct
the excitation from cell to cell far more slowly. This is sufficient
to explain in the simplest possible manner, why the contraction
wave arising in the sinus is not of uniform velocity,- but is delayed
at the limits of the several segments, breaking up into contractions
of sinus, auricles, ventricle, and bulbus arteriosus.

The highly developed automatic excitability of the muscle cells
of the venae cavae and sinus explains why these parts govern the
rhythm of all the remaining segments of the heart, where automatic

ix CAEDIAC MUSCLE AND NERVES 317

activity is slower and weaker. Gaskell observed (as above) that
with localised warming of the sino- auricular and ventricular
segments, acceleration of cardiac rhythm resulted in the first case
only. He therefore concluded that when the heart is functioning
as a whole, the rhythm proper to the less automatic segments
remains latent under normal conditions, and that the more
frequent and powerful rhythm of the more automatic segments
governs the movements of the entire heart. This is the reason
why under normal conditions the contraction wave always travels
in the peristaltic direction from sinus to auricles, from auricles to
ventricle, from ventricle to bulbus arteriosus.

With this view we must again contrast the latest results of
microscopic work, both on the frog's heart (Bethe), and on the
muscular bundle of His in the mammalian heart, where there is
found to be an exceptional abundance of nerve elements (Hofmann).

H. E. Heriiig has recently (1907) modified his previous
opinions, calling attention to other experimental data, which he
thinks are better explained on the neurogenic theory. These are
as follows : —

(a) In the adult mammalian heart there is a segment which,
when isolated from the rest, is incapable of reacting automatically.
This is the auricular appendage of the right auricle. It now /
appears from microscopic researches that this particular part has
no ganglionic nerve elements.

(6) Under certain conditions it can be demonstrated that the
automaticity of the mammalian heart, and its capacity for
reacting to artificial stimuli, are properties independent of one
another. It is possible for a heart in diastolic or systolic arrest to
be more excitable to artificial external, than to automatic internal
stimuli, and vice versa.

(c) A small incision in the region of the orifice of the venae
cavae, or a single induction shock of minimum intensity in the
right auricle, may suspend the automatism of the auricular region
of the heart for a considerable period.

(d) Lastly, Hering has recently discovered that a mammalian
heart arrested from any cause whatsoever, is capable of recom-
mencing its beats in consequence of the stimulation of the
accelerator nerve. He holds that these facts are better explained
on the theory of a nervous, than on that of a muscular auto-
maticity in the adult mammalian heart.

VLL It can be demonstrated independently of the neurogenic
or inyogenic theory of rhythm that cardiac muscle differs from
ordinary skeletal muscle in its peculiar physiological characteristics.
Bowditch (1870) was the first to study in Lud wig's laboratory the
phenomena exhibited by the apex of the heart (attached to a
simple cannula filled with serum, and connected with a recording
manometer), when excited by various agencies.

318 PHYSIOLOGY CHAP.

He found that the apex-beats called out at regular intervals
by induction shocks did not increase in intensity with increased
strength of stimulus, as is the case with normal muscle. When
an induction current, no matter of what intensity, is strong enough
to provoke a contraction, this is invariably maximal, i.e. as strong
as can be obtained from the heart at the given moment (" all or
nothing," Law of Bowditch). This fact, which was fully confirmed
by the observations of Luciani, Kronecker, and Stirling, proves that
the contraction of cardiac muscle depends essentially upon its
inner conditions, and to a much less degree upon the external
stimulus, as if the effect of the latter was limited to enabling the
muscle to serve up a spontaneous contraction, of which it would
not have been capable without such a stimulus.

This view is justified by other phenomena elucidated by
Bowditch. When cardiac muscle is stimulated with weak in-
duction shocks, the reaction sometimes occurs and sometimes fails
(stimolazioni fallaci ). If the strength of stimulus is increased, or
the interval between each is diminished, the number of effective

uiiiiiiuuiuiuii

Fin. 141. — Bowditoh's ascending staircase from frog's heart ligatured at the auricles, with a series
of induction shocks thrown in at intervals of 4". , (Luciani.) The tracing shows a gradual in-
crease of both systolic and diastolic excursions.

shocks increases also. If the current is still further strengthened,
there will be a response to every stimulus (stimolazioni infallibili}.
After a long series of regular contractions a weaker current is seen
to produce the same effect. Hence a strength of current which
js at first uncertain (fallace) becomes certain (infallibile) after
/ P a sequence of shocks. These facts prove that the excitability
of cardiac muscle to external stimuli is very variable, and oscillates
from one moment to another, and that the contractions are capable |
of determining the said oscillations of excitability.

On experimenting with frogs' hearts, ligatured at the auricles,
we obtained the same results with Bowditch's method of electrical
stimulation as he discovered for the apex of the heart.

Another phenomenon that can be observed on experimenting
either with the apex or the auricular ligature, is the so-called
Bowditch staircase. After complete rest for 5 to 10 minutes,
rhythmical excitation with induction shocks of uniform strength,
thrown in at intervals of 4 to 6 seconds, produces a series of
contractions, which steadily increase in height up to a certain
maximum. We were able to demonstrate that Bowditch's stair-
case expresses not merely an increment in systole, but an increment
in diastole also. This means that the prolonged rest produces a

IX

CAKDIAC MUSCLE AND NEEYES

319

certain inertia in the heart, associated with exaggeration of tonus,
and that the electrical stimuli arouse the heart from this state,
when it gradually recovers its activity, systolic as well as diastolic
(Fig. 141).

With regard to the tonicity of cardiac muscle, i.e. the inter-
mediate state between systole and diastole, at the pause, Fano
discovered an interesting phenomenon on the heart of the tortoise
(Emys europea). If one auricle of this animal is connected by a
thread with a writing lever, its spontaneous beats complete them-

FIG. 142. — A and 13, Myograms from auricle of tortoise heart (Emys europea), obtained by sus-
pension method ; showing two different .forms of rhythmical oscillation of auricular tone.
(Fano.)

selves above a line of rhythmical oscillating tonicity. These
automatic oscillations of tone in the auricle are of varying
intensity, and comprise a larger or smaller number of beats (Fig.
142, A and B). If the rhythm of the two auricles is recorded
simultaneously, it will be seen that while the beats are perfectly
synchronous, the oscillations in tone of the two auricles are quite
independent as regards intensity and frequency. When the heart
is exhausted the oscillations in tone are the first to disappear. On

/

C, Oscillations of auricular tone in toad's heart (Bufo viridit) (Bottazzi).
D, The same from heart of Rana esculeuta.

exciting the vagi, the tonic oscillations increase, while the beats
are arrested. These facts led Fano to suggest that the rhythm of
tonicity may be due to the contraction and expansion of a proto-
plasmic substance, other than that which determines the rhythm
of the beats.

Bottazzi observed automatic oscillations in tonus both in the
auricles of the amphibian heart (Fig, 142, C and D) and also on
the sinus venosus, even when they were bloodless. Since he found
the same phenomenon in the oesophagus of amphibia and of the
chick embryo, and Ducceschi has noted it in the stomach of the
dog (organs which consist of muscle cells that are very rich in

320 PHYSIOLOGY CHAP.

sarcoplasm), he thinks the oscillations in tonicity are probably due
to the contractions and expansions of the sarcoplasm, and the
ordinary and more frequent beats to the doubly refractive substance
of these elements.

The oscillations of excitability in cardiac muscle recorded by
Bowditch with electrical stimuli were determined more exactly by

the later work of Kro-
necker and Stirling.
They showed that the
heart becomes inexcit- *T\
able during the time J
of its contraction, and j
that if cooled this in- J /
excitability persists
for some time after
the beat is completed.
These facts were
confirmed by Marey,
who analysed the
phenomenon of peri-
odic inexcitability to
electrical stimuli in
the automatically
beating heart, and
termed it the refcac- .'J
tory phase of the ^
cardiac" cycle. It
corresponds with the
period of systole, and
its duration varies

Fir;. 143.— MyOgrams of frog's ventricle, obtained by Marey with With that of the

apparatus of Fig. 126, and reduced one-half bv photography. afirrmli anrl ntV»oT

Shows effect of excitation by break of induction current, at S™1111. an°- . ®}™X

various moments of the cardiac cycle. The line O indicates extrinSIC Conditions.

the commencement of all the beats, during which the TTT-^I i j_- i •

shock is sent in. In 1, 2, and 3 the heart is refractory to With Weak Stimuli

the stimulus. From 4 to 8 the heart reacts by an extra i_"U0 vafvanfnrv -rVhaeo

systole, by a delay or lost time which is progressivelyless, l .IdUlUl^ JJlld,St;

assh~o\vn by the sections shaded obliquely to make them more riprsists throughout

conspicuous. The extra-systoles increase in height from 4 fl_^ & ., ,

to 8, each being followed by a compensatory pause. At ee, the Systole : With
the line marked by the electric signal, the break induction , f i- •, •

shocks were thrown in. Stronger Stimuli it IS

limited to the first .

period of systole, or obliterated altogether. Warming shortens)/
or suppresses it ; cooling prolongs it. Each forced or extra-
sy stole is more ample in proportion as iT^appears later after
the spontaneous systole that preceded it. The_ extrasystole is
followed by a resting period longer than that which usually occurs
between two syiMes^cprnpejasafe^ipause), byjwhich the temporary
disturbance of cardiac rhythm is adjusted (Fig. 143).

Later observers, who, after Marey, studied the compensatory

ix CAKDIAC MUSCLE AND NEKVES 321

pause which succeeds the extrasystole, attributed it to the
intrinsic nervous system of the heart, because in experiments with,
the apex, where there were supposed to be no ganglia, the extra-
systole appeared, but not the compensatory pause observed upon
the intact heart supplied with ganglia (Dastre, Marcacci, Gley,
Keiser). Subsequently, however, Engelmann showed that the
compensatory pause can be obtained at the apex also, previous
observers having failed to detect it because they employed a
tetanising current as stimulus, instead of single make or break
shocks. He demonstrated that the compensatory pause may fail
in the entire ventricle also, with the constant current. Bottazzi,
on the other hand, observed the compensatory pause on the
embryonic heart of the chick, which excluded the possibility of its
being essentially conditioned by the nervous elements.

It has frequently been noted, on stimulating the heart at the
sino-auricular junction, that not only is it possible to obtain an
extrasystole with weak currents that would be ineffectual beyond ^/
these limits, but that a series of rhythmical beats, of greater
frequency than the normal, may also occur (Langendorff, Keiser).
This was explained by the presence of ganglion cells in these
parts. But in view of Gaskell's discovery that it is just these
parts which contain the more embryonic muscle cells, endowed
with a marked automatic rhythm, the difference observed in the
response may obviously depend rather upon these muscular
elements than upon the ganglia.

The refractory phase of the cardiac cycle accounts for the
regular alternation of systole and diastole, and explains why it is
difficult to produce a true tetanus of the heart by means of a /
tetanising current, i.e. to fuse a number of contractions into a
single very marked and persistent one, as in the case of ordinary
muscle (Kronecker and Stirling).

The direct action of tetanising currents upon the surface of the /
mammalian heart produces the strange effect termed by Ludwig N
and Hoffa (1849) delirium cordis. This is a wholly unco-ordinated
activity of cardiac muscle, in which it contracts at isolated points,
and simultaneously relaxes at others, so that the mechanical work
of the heart becomes impossible. Co-ordinated activity may be
resumed after a delirium lasting for several minutes, but only
when the current has not been unduly strong, nor the stimulation
too prolonged. The origin of this phenomenon has been variously
explained. MacWilliam held it to be independent of nervous
influences, and merely the effect of direct excitation and altered
conduction in the muscle cells. Kronecker, on the contrary, inter-
prets delirium cordis as the functional disturbance of a nervous
centre of co-ordination for cardiac movements, situated in the
upper third of the inter ventricular septum. He showed that in
the dog, and frequently in the rabbit also, it was only necessary

VOL. I Y

322 PHYSIOLOGY CHAP.

to thrust a needle into this spot in order to produce a fatal
delirium of the heart, while any number of punctures at other
points of the ventricle had no effect on the co-ordinated contrac-
tions. The trend of recent evidence in favour of the neurogenic
theory (which has always been upheld by Kronecker for the heart
of mammalia also) increases the presumption for this interesting
hypothesis- of a co-ordinating, ganglionic centre for cardiac rhythm.

VIII. Admitting that the rhythmicity of the heart depends
on the automatic and reflex excitability of its intrinsic ganglion
system, it follows by exclusion that the extracardiac nerve plexus
through which the heart is brought into relation with the cerebro-
spinal axis can merely exert a regulatory function upon the
rhythm, modifying it in accordance with varying external
circumstances and the temporary needs of the body. We must
now investigate the nature of this regulation of cardiac movements
as exercised by the nervous system.

At the Congress of Italian Naturalists at Naples (September

FIG. 144.— Inhibitory effect of electrical excitation of frog's vagus. (Waller.) Thp pa

lation is marked on the abscissa by an electric siimal. At the close of excitation the beats
become larger.

1845) the brothers Weber communicated the results of certain
experiments which they had undertaken on the effect of stimulating
the vagus by tetanising induction currents. To their surprise
they obtained neither acceleration nor reinforcement of the beats
>/ of the heart, but found they were slowed, or arrested in_diaatole.
Stimulation of the intact vagus or its peripheral trunk produced
the same result in all classes of vertebrates (Fig. 144). In the
frog the excitation of the nerve centres from the optic lobes to the
tip of the calamus scriptorius had the same effect. This was a
discovery of capital importance, which cleared the way for a vast
number of other observations. Budge discovered the same facts,
independent of the Webers, and almost at the same moment, but
declared himself unable to decide whether the arrest of the heart
was due to a cardiac tetanus, as he was then inclined to believe,
or to a temporary paralysis of the heart (for which he subsequently
concluded on becoming acquainted with the Webers' communica-§
tion).

Three different views have been advanced in explanation of this
phenomenon : that of the Webers, who regarded the vagus nerves
as the restrainers of the heart ; that of Budge, which was imme-
diately accepted by Schiff and at a lator time by Moleschott, to the

IX

CARDIAC MUSCLE AND NERVES

323

effect that the vagi were motor nerves, easily exhausted by
electrical stimuli ; and, lastly, that of Brown-Sequard, who held
the vagus to be a vasomotor nerve of the coronary system.
Budge's view was soon found to be untenable, since even the
weakest currents retard or arrest the movements of the heart.
Still easier was it to overthrow Brown-Sequard's hypothesis, seeing
that ligation of the coronary arteries does not arrest the heart,
and in the frog's heart, which has 110 cardiac vessels, the vagus
still produces the same effect. Only the Webers' theory, therefore,
remains, and the object of later researches has merely been to
determine the mode and
mechanism by which the
retardation or inhibition
of the beats is effected in
vagus stimulation.. The
most important results of
these observations are
briefly stated as follows:—

In warm-blooded ani-
mals the standstill brought
about by the vagus never
lasts more than a minute.
If the curve of arterial
pressure is registered dur-
ing vagus excitation by
Ludwig's kymograph, a
more or less rapid depres-
sion may be observed,
according as arrest (Fig.
145), or merely slowing
of the beats (Fig. 146), is
obtained. The inhibitory
action is more pronounced
in mammals than in birds,
where as a rule there is only delay (Claude Bernard), or arrest
of a few seconds (Wagner, Meyer). In the poikilo thermic verte-
brates, on the other hand, the standstill is more pronounced than
in mammals.

Cardiac arrest by vagus stimulation has repeatedly been
determined on man. Henle obtained it in 1852 on a decapitated
criminal, whose right auricle was still beating (ultima moriens) ;
Czermak, Thanhoffer, Concato, Malerba, Wasilewsky, Cardarelli
obtained it by compression or friction of the neck along the course
of the vagus and the carotids. This is an experimentum peri-
culosum, since it may produce disquieting systems of syncope
(Thanhoffer).

The latent period of vagus excitation is comparatively long,

FIG. 145. — Depressor effect of strong excitation of vagus
in dog. (Morat.) The period of stimulation is marked
at E on the abscissa. The carotid is connected with
Ludwig's kymograph.

324 PHYSIOLOGY CHAP.

the effect being usually manifested only after a heart-beat (Schiff,
Pfliiger and others), as shown in Figs. 144, 145, 146.

Excitation by a single induction shock has little effect ;-
constant currents usually produce retardation only; tetanising
induction currents are the most effective (Bonders, Heidenhain,
etc.).

Stronger currents produce a more obvious and prolonged in-
hibition ; minimal currents always produce delay, never accelera-
tion of rhythm, contrary to the observations of Moleschott (v.
Bezold, Pfliiger, Rosen thai, etc.). The frequency of the induction

FIG. 140.— Depresaor effect of moderate excitation of frog's vagus. (Tigerstedt.) The two vertical
lines indicate the duration of stimulation. Carotid connected with Lud wig's kymograph.

shock tells more than intensity of the stimulus (Legros and
Onimus).

A difference in the inhibitory action of the two vagi has often
been observed, particularly in amphibia (Meyer, Gaskell, Mac-
William, Wesley Mills, Tarchanoff). In the rabbit the right
vagus is often more effective than the left (Masoin). The same
has been found in the horse and dog (Arloing and Tripier), and
also in man (Czerrnak).

When on cessation of the arrest produced by the stimulation
of one vagus the other is at once excited, an effect similar to the
first is produced, without any resting period, if the first nerve had
not been unduly fatigued (Tarchanoff, Eckhard, Mac William and
others).

IX

CARDIAC MUSCLE AND NERVES

325

Besides the modifications of rhythm (Engelniaim's chronotropic

effects) it is important to consider the changes produced by

vagus excitation on the amplitude of the beats, or more exactly,

on the degree of systolic contraction and diastolic expansion

(inotropic effect).

Coats was the first (1869). to note that the excitation of the
[vagus obstructed systole
land favoured diastole.

He found by exact ob-

servations, carried out in

Ludwig's laboratory on

the frog's heart in situ,

connected with a record-

ing manometer, that

vagus stimulation, with-

out moderating the

ble suspension. (Gaskell.)
vagus in section between

Fin. L47i— Myographic tracing of frog's heart : A, Auricles,
, ventricle, with method of double sus{

Electrical excitation of tlu

the two vertical lines. Shows arrest of beats, both in
auricle and ventricle, which continues after the close of
stimulation ; the beats subsequently recommence, and
become rapidly larger than they were before stimu-
lation.

not iiifrpnnpntl
11UL1I ntl)

diminished systolic con-
* traction and augmented
the diastolic expansion.
It was on these and other
phenomena observed in the dog, in relation to the aspiration of
the heart, which increases during vagus excitation, that we in
1871 based the first principles of our theory of active diastole (see
Chap. VII. 8).

Coats's results were fully confirmed and better worked out in
1882 by Heidenhain and Gaskell. The former found, on stimu-

FIG. 148. — Myographic tracing of frog's heart as in preceding figure. (Gaskell.) In this case, vagus
stimulation does not arrest the beats, nor retard them, but diminishes their amplitude.

lating the vagus with induction shocks thrown in at intervals of
two to five seconds, that the systoles -almost disappeared without
diminishing in frequency.

Gaskell found that vagus arrest only occurs in the frog when
the heart is well nourished, and fails to come off when it is slightly
fatigued. Figs. 147 and 148 represent two curves obtained by

326 PHYSIOLOGY CHAP.

Gaskell, from the frog's heart, in which the inotropic negative
effects of vagus stimulation on the auricles and the ventricle are
simultaneously recorded. The greater diastolic relaxation pro-
duced by the vagus is not necessarily associated with diminished
frequency and height of systole, since it occurs also when vagus
stimulation produces no change either in frequency or intensity of
the contractions. This fact, which has been substantially con-
firmed for mammalia by the researches of Mac William, Johannson
and Tigerstedt, Franrois-Franck, and especially by Stefani (Chap.
VII. 8) completely justifies us in applying the term of diastolic
nerves to the vagi. We shall presently consider the nature of the
process by which the vagus actively incites the cardiac diastole.

In addition to producing negative chronotropic and inotropic
effects, the stimulation of the vagus can also impede the conduc-
tion of the contraction wave, or, in Engelmann's nomenclature, can
produce negative dromotropic effects.

NueT found in the frog, on recording the contractions of the
auricle and ventricle separately, by means of writing levers
connected to those parts of the heart by threads, that vagus
excitation acts more easily on the auricle than on the ventricle.
Gaskell, on the other hand, has frequently observed the opposite
effect, i.e. that the ventricular contractions almost disappeared,
while the auricular contractions increased. In the land tortoise,

(he failed to establish any action of the vagus on the ventricle,
while the contractions of the auricles were much reduced, without
any slowing of rhythm. Wesley Mills again found in certain
amphibia, reptiles, and fishes that the effect of the vagus was
greater on the auricles than on the ventricle ; Mac William, how-
ever, found the opposite on other animals. We cannot at present
give any explanation of these phenomena.

Other facts, on the contrary, show clearly that vagus excitation
diminishes conduction of excitation from one segment of the heart
to_a,agJilier. Gaskell noted in tortoises that stimulation of the
right vagus had no effect on the beats of the sinus venosus, while
it brought the auricles and ventricle to a complete standstill. In
mammalia, Mac William observed cases in which the auricles beat
with a more frequent rhythm than the ventricles ; the excitation
was not propagated from the first to the second segment, although
the excitability of the ventricles was undiminished. Bayliss and
Starling finally discovered a method by which it is easy to show
that the stimulation of the vagus produces negative dromotropic
effects. They induced an artificial rhythm of the heart by direct
excitation of the auricles three to four times per second, and then
found that a gentle excitation of the vagus sufficed to reduce the
number of ventricle beats to half the number of those of the
auricle, or even stopped them for a short time, while the auricle
beats continued.

ix CAKDIAC MUSCLE AND NEKVES 327

Some observers have stated that during the arrest of cardiac
movements produced by vagus stimulation the heart becomes
inexcitable to direct artificial stimuli (Schiff, Eckhard, Mill).
Mac William, on the other hand, observed that when, in mammals,
vagus excitation produces not arrest, but pronounced weakening
of the systole (negative inotropic effect), the value of the threshold
of excitation, or least minimal efficacious stimulus applied directly
to the auricles, rises, i.e. the excitability of the myocardium is
lessened. Engelmann found, on the contrary, in the frog's heart
that during the inotropic negative effects due to stimulation of
the vagus, excitability of the auricles to direct stimuli may remain
unaltered, and even sometimes be augmented, which he terms the
positive bathmotropic effect. Engelmann, however, admits (experi-
menting always with the frog's heart) a great variety in the results
of his researches. The most frequent case is the association of
negative inotropic with negative bathmotropic effects ; but other
cases are to hand of simultaneous positive bathmotropic and
positive inotropic effects. At other times vague excitation gives
rise now to inotropic and now to bathmotropic actions.

On the strength of this last fact more particularly, Engelmann
holds that the changes of excitability in cardiac muscle (bathmo-
tropic influence) are of a primary nature independent of the
simultaneous inotropic influences. This opinion is, however,
contradicted by H. E. Hering, who holds the bathrnotropic effects
to be secondary and dependent on changes in the duration of the
systole.

DL^The discovery that the heart receives accelerator or
systolic branches of the sympathetic in addition to the inhibitory
or diastolic fibres of the vagus was made in 1862 by V. Bezold, and
worked out more accurately by Bevor (1866). On dividing the
two vagi and cervical sympathetics in rabbit, excitation of the
medulla oblongata and cervical cord produced a rise of blood
pressure, with acceleration of cardiac rhythm. On repeating the
same experiment after dividing the cord between the first and
second vertebra (with the object of cutting out the influence of
the bulbar vaso-motor centre of Ludwig and Thiry), acceleration
was obtained without rise of pressure. There must accordingly be
accelerator nerve fibres running from the cervical cord through
the rami communicantes of the sympathetic to the heart. Yon
Bezold afterwards demonstrated that these accelerator fibres pass
through the last cervical ganglion, and thence to the heart.

The brothers Cyon obtained the same results in 1866, on
dividing the splanchnics instead of the cord ; and further observed
that when the first thoracic ganglion was destroyed, there was no
longer acceleration of cardiac rhythm.

Schmiedeberg (1870) detected the presence of accelerator fibres
in the frog also, running with the vagus ; after a mild dose of

328

PHYSIOLOGY

CHAP.

atropine or nicotine, stimulation of these nerves no longer causes

inhibition, but only acceleration of

rhythm. Heidenhain (1882) and

Gaskell (1884) subsequently showed

that the accelerator fibres are

derived from the sympathetic, and

unite with the latter immediately

after the vagus leaves the cranium

(Fig. 149).

In 1871 Schniiedeberg, with
Ludwig, studied the topography

IX

FIG. 149.— Left. Diagram of frog's cardiac nerves. (After, Foster.) fif, Vagus roots ; PC, cranial
wall; GV, vagus ganglion; IX, glosso-pharyngeal ; VS, vago-sympathetic ; Sc, cervical sym-
pathetic, which unites with vagus ganglion ; sc, sympathetic branch which traverses the
cranium and gives off fibres to the Gasserian ganglion ; Gci, first sympathetic ganglion receiv-
ing fibres from first spinal nerve; AV, annulus of Vieussens traversed by subelavian artery;
<rs, second sympathetic ganglion receiving fibres from second spinal nerve ; Gm, third sym-
pathetic ganglion, which receives fibres from third spinal nerves, ;i°nr, via ramus communicans,
re. The direction of the arrows indicates direction, first ascending, then descending, in which
the excitation of the cardiac fibres by the vago-spinal nerves is transmitted to the heart.

FIG. 150. — Right. Diagram of cardiac nerves in dog. (After Foster.) The upper portion of the figure
represents the inhibitory fibres, the lower part the accelerators ; rV, roots of vagus ; rS, roots
of spinal accessory, the internal roots of which, shown by black line, run in the trunk of the
vagus, V ; GJ, jugular ganglion ; Gtv, ganglion of vagus trunk ; V, trunk of vagus united with
cervical sympathetic to form vago-sympathetic nerve ; Sc, cervical sympathetic ; Gci, inferior
cervical ganglion ; AV, annulus of Vieussens traversed by subclavian artery ; GS, stellate or
first thoracic ganglion ; tic, cardiac nerves, of which the two tipper branches come from the
accessory or spinal, and the two lower from the first to the fifth thoracic nerves (particularly
from second and third, as shown by black lines), the fibres of which ascend by rami com-
municantes to the stellate ganglion and from the loop of Vieussens. The direction of the'arrows
indicates the direction, first ascending, then descending, in which the activity of the cardiac
nerves travels to the heart.

of the cardiac plexus in the dog, and distinguished the inhibitory
from the accelerator fibres (Fig. 150).

ix CARDIAC MUSCLE AND NERVES 329

The inhibitory fibres arise in the accessory or eleventh cranial
nerve. After extirpation of this nerve in the dog, and lapse
of . sufficient time for the peripheral fibres running with the
vagus to degenerate, vagus stimulation produces no effect upon the
heart, as was shown by Waller in 1S56, and subsequently con-
firmed by Schiff, Heidenhain, and Francois-Franck. Giannuzzi,
however, found that vagus excitation still produced a slight
moderator effect fourteen days after extirpation of the accessory
nerve, which he ascribed to certain fibres belonging to the vagus
itself, with the same function as those of the accessory.

The accelerator fibres unite the lower cervical with the first
thoracic (or stellate) ganglion. They, too, emerge from the cord
(according to Strieker, in the first six thoracic nerves), and pass by
the ranii communicantes to the sympathetic system. Albertoni
and Butalini found the third dorsal nerve particularly effective

Fio. 151. — Acceleration of heart-beats by brief excitation at E of the two branches of the nerve
that form the annulus of Vieussens, in curarised ilog. (l)oyon.) Carotid connected- with
Ludwig's kymograph.

(Fig. 151). The cervical trunk of the vagus also seems to con-
tain some accelerator fibres, as shown by the action of atropin
(Rutherford).

The functional character of the accelerator fibres was studied
by Heidenhain and Gaskeli on poikilotherrnic, and by Schmiede-
berg, Bowditch. Baxt, Boehm, Fran^ois-Franck, E. Voit, and Roy
and Adaini more particularly on warm-blooded animals. Their
results may be summarised as follows : —

Excitation of the accelerators manifests itself after a rather s
long latent period, which may amount to two seconds. The *
maximum of acceleration (positive chronotropic effect) first appears
after ten or more seconds. The effect of a brief excitation is
therefore shown when it is over, as an- after-effect. This lasts for
a considerable time, exceeding two •seconds. The duration of
acceleration depends on the length of stimulus, since the accelera-
tors are hard to fatigue, even with an excitation lasting for two
minutes.

330 PHYSIOLOGY CHAP.

The acceleration may rise from 7 per cent to a maximal
70 per cent, according to the prevailing frequency of rhythm.
The difference in effect depends principally on the frequency of
rhythm previous to excitation. The maximum of acceleration is
not increased when the accelerators on both sides are excited
simultaneously. The duration of the after-effect is in proportion
with the duration of the stimulus.

The positive inotropic and dromotropic effects must be dis-
tinguished from acceleration or positive chronotropic effects.
Heidenhain and Gaskell observed on the frog that stimulation of
the sympathetic fibres increases the height of systole and shortens
diastole by raising the tonicity of cardiac muscle (inotropic effect) ;
the capacity of the latter to transmit the excitation from one segment
to the next (dromotropic effect) also increases ; the effects from
every point of view are antagonistic to those of the vagus. These
facts are confirmed in essentials by thQ investigation carried out

Fie. l'-2. — Augmentation of ventricle beats of dog after electrical tetanisation of first left acceler-
ator nerve, as traced on abscissa. (Franc.ois-Franck.)

with various experimental methods on mammals by Frangois-
Franck, Boy and Adami, Bayliss and Starling. They appear to
justify the physiological name of systolic nerves given by us to
the cardiac branches of the sympathetic, in opposition to the
diastolic nerves or cardiac fibres of the vagus (Fig. 152).

When these two nerves (which seem to be antagonistic in
function) are excited simultaneously, the effects are not algebraic-
ally summed up and cancelled, but both are expressed, — fir,&t-thoj>e
propgr to the vagus^-then^those^ from the_syjmpajih^tic^ This
remarkable fact was discovered on the dog" by Baxt (1875) in
Ludwig's laboratory. It can also be observed when the vagus is
excited with minimal induction currents, and the sympathetic with
strong currents to produce maximal effect (Fig. 153). The probable
interpretation, according to Baxt, is that the two kinds of nerve
fibres act upon the heart at two different points. During the
excitation of the diastolic nerve the fibres of the systolic nerve
cannot act, the excitability of the cardiac muscle being modified ;
they will confine themselves to storing up the latent excitability
in the ganglion, to appear as an after-effect at the close of

IX

CAEDIAC MUSCLE AND NERVES

331

stimulation. It should, however, be stated that the experimental
data of Baxt, and his interpretation, have to some extent been
corrected by the subsequent work of Meltzer (1897), Reid Hunt
(189*7), and Engelmann (1900) ; who demonstrated that the effects
consequent on the simultaneous stimulation of the two distinct
cardiac nerves are more varied and complex than was supposed by
Baxt, and that the chrono- and iso tropic may be complicated by
dromotropic effects.

X. After defining cardiac inhibition due to stimulation of the
vagus as a diastolic effect, in so far as it favours diastole and

FIG. 153.— Diagram representing frequency of cardiac beats after excitation of vagus (continuous
broarl line), accelerator nerves (continuous thin line), and of both nerves (dotted line).
(Baxt.) The stimulation of the accelerators lasts from a to e, (16"), that of the vagus from d
to e (4"), and commences 12" later. Time marked in seconds on the abscissa ; number of beats
occurring in each 2" shown on areas of ordinates.

obstructs systole, and the acceleration due to the sympathetic as a
systolic effect, in-so far as it favours systole and obstructs diastole,
we still have no definite idea of the inner mechanism of these
phenomena. As, according to the supporters of the myogenic
doctrine, the automatic rhythm of the heart is a property inde-
pendent of the nervous system, inherent in the muscle cells of the
myocardium, it is logical to assume that the two kinds of nerve
which influence the heart from without determine opposite results,
inasmuch as they alter the metabolism of the muscle cells — which
underlies autoinaticity — in an opposite direction. This was
established by Gaskell (1887) in his important discovery of the

332 PHYSIOLOGY CHAP.

electrical phenomena that accompany the inhibitory processes,
and are the converse of those concomitant with the accelerator
processes.

The intact and the resting heart are iso-electric. When any
point of the walls is injured, or excited, by any cause, that point
becomes galvanometrically negative in relation to the intact, or
inacjdye,_parts : and on connecting the injured, or active, point
with any other intact, or inactive, point, a current known as the
demarcation, or action, current passes through the galvanometer
(Hermann).

Now Gaskell has shown that if the heart of a tortoise is
arrested by the upper Stannius ligature, and the tip, of the auricle
killed with hot water, then on leading off the demarcation current
to the galvanometer, and exciting one of the branches of the vagus
(running with one of the coronary veins from the sinus venosus
to the auriculo-ventricular groove), a positive variation, i.e. an
increase of the demarcation current, is apparent. Since this effect
cauuot be due to increased (galvanometric) negativity of the
dead point, we must assume that it is the result of augmented
(galvanometric) positivity of the intact part. We must therefore
conclude that excitation of the vagus in a resting heart produces
modifications of its metabolism, expressed in an electrical variation,
opposed to that which occurs in the contraction of cardiac muscle.

According to Gaskell, the altered metabolism produced by
vagus excitation consists in an increase of reparatory or anabolic
processes ; while the stimulation of the sympathetic fibres accelerates
the disintegrative or katdbolic processes. The action of the vagus
is therefore diastolic because it promotes anabolic processes, while
that of the sympathetic is systolic because it promotes the katabolic
processes. The probability of this theory is attested by the fact
that^ vagus excitation is followed by a phase of increased activity
as its" after-effect, showing that the cardiac muscle is strengthened,
not weakened, while, on the other hand, excitation of the sym-
pathetic is followed by breaking-down, consumption, and exhaustion
of the myocardium (Gaskell). The anabolic action of the vagus
'is, as we have seen, associated with diminished reflex excitability
of the cardiac muscle (negative bathmotropic effects), so that the
latter on direct stimulation no longer reacts by a contraction, save
when the stimulus is excessive. This fact explains the mechanism
of active diastole, as determined by the vagus ; it is the effect of
the lowered excitability of the myocardium, by which systole is
hindered, and diastolic expansion of the muscle cells promoted.

Other facts described at different times by various authors
harmonise with Gaskell's theory (which Fano was the first to
bring forward in Italy). Panum and Giannuzzi observed on the
rabbit that weak stimulation reinforced a previously weakened
cardiac activity. Traube noticed that on interruption of artificial

ix CAEDIAC MUSCLE AND NEKVES 333

respiration in curarised animals, the heart beat longer when the
vagi were intact than when they had been previously divided.
Brown-Sequard found on bleeding two rabbits, in one of which the
vagus had previously been excited, in the other not, that asphyxia
and eventual arrest of the heart were produced more rapidly in
the second than in the first. Konow and Stenbeck stated that
the rabbit's heart in situ, but completely isolated from the central
nervous system, beat for a shorter time, in consequence of asphyxia,
.than when the vagi were left intact and the spinal cord destroyed.

Lastly, the anabolic action of the vagus was confirmed by the
nutritional disturbances that occur in cardiac muscle some time
after the division of these nerves. Eichhorst observed in birds,
and Wasilieff in rabbits, that the division of the vagi resulted in
a certain degree of fatty degeneration of the myocardium. The
results obtained by Fantino and Timofeew were, however, more
convincing. The former confined himself to cutting one vagus, so
that the operated animal remained alive for a longer period.
After killing this animal he found nothing remarkable at the post
mortem, except the atrophy and non-fatty degeneration of the
muscle cells, localised in various regions, according as the right or
left vagus had been divided. Timofeew divided the right vagus
below the recurrens, and the left eight days later. The animal only
survived the second operation three to five days. Death ensued
from adynamia cordis, owing to degeneration of the cardiac
muscle, induced by the failure of the anabolic action of the vagus.

The value of these positive data cannot be impaired by the
negative results obtained on the frog by Bidder and Klug, since
the metabolism of these animals is so sluggish, that they could
survive inanition for many months.

XL We must next investigate the processes by which the
systolic and diastolic nerves of the heart regulate the cardiac
rhythm. It has long been known that the heart sends information
to the nerve centres of all modifications in its functions, but the
study of its afferent nerves is more recent. While investigating
the physiological function of the different branches of the cardiac
plexus in the rabbit (1886) Ludwig and Cyon discovered a branch,
which they termed the depressor nerve. It arises, as shown in
Fig. 154, from two roots. Its division produces no change in
cardiac rhythm, which proves that it is not in tonic excitation.
Stimulation of its peripheral end has no effect, showing that it
contains no fttfeqant fibres. Excitation of the central end lowers
arterial blood pressure, and simultaneously retards the beats of the
heart. After division of the vagi this last effect is abolished,
while the first remains. The slowing of the rhythm must there-
fore be a vagus reflex, and the arterial depression a reflex by way of
the vaso-dilators. The depression of blood pressure continues after
cutting out both vagi and the ganglion stellatum. Accordingly,

334

PHYSIOLOGY

CHAP.

it cannot depend on the centrifugal nerves of the cardiac plexus.
After dividing the splanchnic nerve the depressor effect is much
less. The vascular dilatation must, therefore, take place largely
in the vessels controlled by this nerve, and only in a minor degree
in other vessels.

These results were confirmed and extended by various observers
on the cat, horse, dog, and pig. In poikilothermic animals no
separate depressor nerves could be discovered.

FIG. 154. — Exposed nerves of rabbit's neck. (Doyon and Morat.) nv, Vagus nerve ; nd, depressor
nerve, arising above in two brandies, one given off from the vagus trunk, the other from the
superior laryngeal ; nls, superior laryngeal nerve ; nil, inferior or recurrent laryngeal nerve ;
bes, external branch of spinal nerve ; ni, hypoglossal ; gcs, superior cervical ganglion ; sc, cervi-
cal sympathetic ; gci, inferior cervical ganglion ; etc, carotid artery ; oas, axillary ganglion ;
md, digastric muscle ; msi, stylo-hyoid muscle.

Attempts were made to determine the exact peripheral distri-
bution of the depressor nerve. Wooldridge and Kazem-Beck
believed that its fibres entered the walls of the ventricle ; more
recently Koster and Tschermak (1902) discovered that its nerve-
endings lay in the wall of the aorta.

It is highly probable that the depressor (which, as we have
said, is not in tonic excitation) is only excited when the pressure
in the aorta becomes excessive, and obstructs the systolic evacua-
tion of the heart. The vessels then dilate, pressure falls, and the

ix CAKDIAC MUSCLE AND NEEVES 335

resistance which the heart has to overcome is reduced. The
retarded rhythm tends to the same result.

Some interesting experiments of Sewal and Steiner illustrate
this theory. On ligaturing the two carotids they observed a rise
of arterial pressure, which was obviously nervous in origin, since it
failed when the vagi had previously been divided. When, on the
contrary, the depressors alone had been cut before ligaturing the
carotids, a much greater pressor effect was obtained than with the
intact depressors. They concluded that the depressors are highly
sensitive to any increase of mechanical resistance presented to the
functions of the heart.

In studying blood pressure during asphyxia, Konow and
Stenbeck saw that it was far more irregular when the depressors
had been previously divided than when they were left intact, a
proof of their importance in the regulation of the circulation.

Direct proof that the rise in aortic pressure stimulates the
depressors, independent of cardiac influence, was obtained by
Koster and Tscherniak (1902). They showed that even in the
isolated heart the passive distension of the walls of the aorta, on
filling it rapidly with artificial fluid, produced stimulation of the
depressors, as exhibited in a negative variation (action current) of
the demarcation current led off from two points of the nerve.

Spallitta and Consiglio endeavoured to ascertain whether the
depressor fibres run with the vagus or the accessory. After
dividing the ramus intern us of the accessory, they found that
excitation of the depressors produced a fall of blood pressure, but
no slowing of cardiac rhythm. The depressors accordingly contain
two kinds of fibres : one set cause reflex dilatation of the vessels,
and belong to the vagus ; the other reflexly excites the inhibitory
centre of cardiac rhythm, and runs in the accessory. Mirto and
Pusateri confirmed these results by histological methods. After
intracranial section of the roots of the accessory nerve they found
degenerated fibres in the depressor.

The afferent fibres from the heart are incapable of conveying
clear or conscious sensations. This was shown by Harvey's
experiments on the exposed heart of Viscount Montgomery. The
indefinite malaise complained of in the cardiac region by cardio-
paths (v. Ziemssen) may result from compression of the sensory
nerves beyond the heart. Although incapable of arousing
conscious sensations, the centripetal cardiac nerves are able
reflexly to produce more or less diffuse movements of the skeletal
muscles. Budge, Goltz, Gurboki, on pinching the heart in rabbit
and frog, obtained these reflex movements, which failed when
the vagi had been divided.

Even such afferent fibres of the vagus as do not belong to the
heart reflexly modify cardiac rhythm. If the central end of one
divided vagus is stimulated while the other is intact, a delayed

336 PHYSIOLOGY CHAP.

rhythm is obtained, which does not appear after cutting the other
vagus (v. Bezold, Drechsfeld, Aubert and Koever, etc.). The
various pulmonary branches of the vagus were stimulated, accord-
ing to Hering, by insufflating the lungs with open thorax,
producing, acceleration of cardiac rhythm, which is absent with
division of the cervical vagi. The acceleration of pulse which
Sommerbrodt observed in man after screaming, singing, coughing,
inhaling of compressed air, is due to the same cause, i.e. to
abnormal rise of bronchial pressure.

Central excitation of the superior laryngeal, as also stimulation
of the laryngeal inucosa above the vocal cords, produces arrest or
slowing of the heart-beat with intact vagi (Franc^ois-Franck).
This does not occur with centripetal excitation of the inferior
laryngeal, or on stimulation of the laryngeal mucosa below the
vocal cords.

On exciting the, abdominal sympathetic by repeated taps of
moderate strength on the belly wall, slight inhibitory phenomena
are readily obtained on the frog (Goltz).

The sensory branches of the posterior spinal roots have a double
reflex action on the heart, either a slowing (Cl. Bernard, Frangois-
Franck), or an acceleration of rhythm (Asp). Central excitation
of the sciatic plexus by mechanical stimuli provokes inhibition, by
electrical stimuli, acceleration. The muscular nerves also produce
opposite effects : the same thing produces inhibition with a strong
stimulus, acceleration with a weaker one. When chemically
excited (e.g. by inhalation of chloroform), the sensory fibres of the
trigeminus readily induce slowing and even arrest of the heart, and
syncope, which has a great practical significance. The nerves of
the special senses also act in this twofold way upon the heart.

XII. The afferent nerves of the heart affect the efferent
through centres which determine the reflex effects.

The centre of the diastolic nerves is in the bulb or medulla
oblongata (E. Weber, Budge). In the frog it extends from the
optic lobes to the tip of the calamus scrip torius. In the rabbit
it is apparently confined to the bulb (Frangois-Franck). In the
cat there is about half-way up the rhomboid sinus, a point at
which excitation by a needle produces arrest or slowing of the
heart (Laborde).

The centre for the systolic nerves has up to the present not
been exactly located. The whole upper section of the cervical
cord reacts by acceleration of cardiac rhythm^

Although the paths are not yet exactly determined, it must
be remembered that the cardiac centres are in connection with
the cortical and subcortical centres of the brain. The influence
of psychical states upon the heart is undeniable ; some people
even have the faculty of voluntarily influencing their heart-beats.

It is probable that under normal conditions the cardiac

ix CAEDIAC MUSCLE AND NERVES 337

centres are in continuous slight excitation, on which depends the
tone of the vagi, exhibited in the acceleration of* the beats, on
simple division of that nerve, or administration of atropin. This
effect does not appear when section of the vagus is preceded by
division of the cervical cord (Bernstein). Acceleration is also
obtained after dividing the splanchnic nerve (Asp), due not
to the lowering oT blood pressure, which usually produces the
opposite effect, but to the depression of vagal tonus. In the
newborn, tonicity seems to be wanting in the vagus till after the
second week, since in kittens neither section of the vagus nor
exhibition of atropine causes acceleration of pulse (Soltmann).

It is possible that the systolic nerves and centres also have
normally a certain tonicity, although subordinate to the diastolic
nerves. After extirpation of the lower cervical and stellate
ganglia on both sides, there is, when the vagi are divided, a
marked acceleration of rhythm (Tschirjew, Strieker, and Wagner).
With intact vagi, a permanent slowing of beat can be obtained
on dividing the accelerators (Timofeew).

The tone of the cardiac centres and nerves may be automatic or
reflex, or as is most probable, automatic and reflex in character. It
is known that the frequency of cardiac rhythm normally stands
in inverse ratio to the height of the average arterial blood pressure,
i.e. that rise of blood pressure produces lowering of pulse frequency
and vice versa. After section of the vagi this ratio is no longer
so distinct and constant, showing that the blood-pressure regulates
the tone of the cardiac nerve centres, those of the vagus in
particular, directly or reflexly.

BIBLIOGRAPHY

In addition to previous Bibliographies, see also : —

Fundamental Memoirs in re Physiology of Cardiac Muscle and Intracardiac
Nervous System : —

STANNIUS. Arch. f. Anat. u. Physiol., 1852.

ECKHAKD. Beitrage zur Anat. und Physiol. Giessen, 1858-60. Experimentelle

Physiol. des Nervensystems. Giessen, 1866.
GOLTZ. Arch, fur path. Anat., 1860-62.
BOWDITCH. Ber. d. sachs. Ges. d. Wiss., 1871.
LUCIANI. Ber. d. sachs. Ges. d. Wiss., 1873. Edizione italiana, Rivista clinica

di Bologna, 1873.

KRONF.CKER und STIRLING. Beitrage zur Anat. und Physiol., 1874.
MAREY. Compt. rend., 1879.

GASKELL. Aruh. de physiol. normale et pathologique par Brown-Sequard, 1888.
FANO: Lo Sperimentale, 1885. Archivio per le scienze mediche, 1890. Archives

ital. de biologic, 1888.

ENGELMANN. Arch, neerlandaises, 1893-97. Arch. f. Anat. u. Physiol., 1902.
KRONECKEK. Zeitschrift fiir Biologie, 1897.

BOTTAZZI. Pubblicazioni del R. Istituto di Studi superiori di Firenze, 1897.
H. E. HERING. Pfliigers Arch. Ixxxvi , 1901 ; cxv., 1906 ; cxvi., 1907.
A. J. CARLSON. American Journal of Physiology, xii., 1905.
F. B. HOFMANN. Nagel's Handbuch der Physiol. i., 1905.
M. HUMBLET. Arch, intern, de Physiol., 1904, i.
E. VON CYON. Die Nerven des Herzens. Berlin, 1907.

VOL. I Z

338 PHYSIOLOGY CHAP.

Physiology of Intracardiac Nerves and Centres that control the Functions of the

Heart :—
E. WEBER. Annali universal! di medicina di Omodei, 1845. Handworterbuch dec

Physiol., 1846.

BUDGE. Handworterbuch der. Physiol., 1846.
SCHIFF. Arch. f. phys. Heilkunde, 1849.

v. BEZOLD. Untersuchungen iiber die Inner vation des Herzens. Leipzig, 1863.
LUDWIG und CYON. Ber. d. sachs. Ger. d. Wiss., 1866.
COATS. Ber. d. sachs. Ges. d. Wiss., 1869.
ScHMIEDEBERG. Ber. d. sachs. Ges. d. Wiss., 1870.
BAXT. Arch. f. Anat. u. Physiol., 1877.
HEIDENHAIN. Arch. f. d. ges. Physiol., 1882.
GASKELL. Philosophical Transactions, 1882. Journal of Physiol., 1882-87.

Beitrage zur Physiol., C. Ludwig gewidmet. Leipzig, 1887.
FRANCO i s-FuANCK. Travaux du laboratoire de Marey, 1880.
PAWLOW. Arch. f. Anat. u. Physiol., 1887.

Chemical Conditions essential to the Survival of the Isolated Heart :—

H. OEHRWALL. Arch. f. Anat. u. Physiol., 1893. Skandin. Arch, vii., 1897.

G. I. GOTHLIN. Skandin. Arch. f. Physiol. xii., 1902.

H. WINTERSTEIN. Zeitsch. f. allgeni. Physiol. iv., 1904.

0. LANGENDORFF. Arch. f. Anat. und Physiol., 1884. Pfliigers Arch., 1895, Ixi.;
1899, Ixxviii. Herznmskel und intrakardiale Iiinervation. Ergebnisse der
Physiol., 1. Jahrg., 2. Abt. (322 other works cited). Neuere Untersuchungen
iiber die LTrsache des Herzschlages, Ibidem, 1905 (73 other recent works
cited).

S. BAGLIONJ. Zeitsch. f. allgeni. Physiol. vi., 1907.

LOCKE and RoSENHElM. Journal of Physiology, xxxvi., 1907.

E. L. BACKMAX. Festschrift!'. 0. Hanimarsten, 1906.

Recent English Literature : —

E. C. WALDEN. Comparison of the Effect of certain Inorganic Solutions and

Solutions containing Serum Albumin on the Rhythmic Contractility of the

Frog's Heart. Amer. Journ. of Physiol., 1900, iii. 123.
J. A. MAC WILLIAM. Further Researches on the Physiology of the Mammalian

Heart, Part I. On the Influence of Chloroform upon the Rate of the Heart-
beat, etc., etc. Journ. of Physiol., 1899-1900, xxv. 233.
A. W. CAUMAN. The Position of the Respiratory and Cardio-inhibitory Fibres in

the Rootlets of the 9th, 10th, and llth Cranial Nerves. Journ. of Physiol.,

1900-1901, xxvi. 42.
T. G. BRODIE and A. E. RUSSELL. On Reflex Cardiac Inhibition. Journ. of

Physiol., 1900-1901, xxvi. 92.
D. J. LINGLE. The Action of certain Ions on Ventricular Muscle. Amer.

Journ. of Physiol., 1901, iv. 265.
W. H. HOWELL. An Analysis of the Influence of the Sodium, Potassium, and

Calcium Salts of the Blood on the Automatic Contractions of Heart Muscle.

Amer. Journ. of Physiol., 1902, vi. 181.

D. J. LINGLE. The Importance of Sodium Chloride in Heart Activity. Amer.

Journ. of Physiol., 1903, viii. 75.

R. S. WOODWORTH. Maximal Contraction, Staircase Contraction, Refractory
Period and Compensatory Pause of the Heart. Amer. Jourii of Physiol.,
1903, viii. 213.

E. G. MARTIN. An Experimental Study of the Rhythmic Activity of Isolated

Strips of the Heart-muscle. Amer. Journ. of Physiol., 1904, xi. 103.
E. G. MARTIN. The Inhibitory Influence of Potassium Chloride on the Heart,

and the Effect of Variations of Temperature upon this Inhibition and the

Vagus Inhibition. Amer. Journ. of Physiol., 1904, xi. 370.
A. J. CARLSON. Contribution to the Physiology of the Heart of the California

Hagfish (Bdellostoma Dombeyi}. Zeitschr. f. allgeni. Physiol., 1904, iv. 259.
A. J. CARLSON. The Nervous Origin of the Heart-beat in Limulus, and the

Nervous Nature of Co-ordination or Conduction in the Heart. Amer. Journ.

of Physiol., 1905, xii. 67.

ix CAKDIAC MUSCLE AND NERVES 339

A. J. CARLSON. Further Evidence of the Nervous Origin of the Heart- beat in

Limulus. Amer. Journ. of Physiol., 1905, xii. 471.
S. R. BENEDICT. The Role of certain Ions in Rhythmic Heart Activity. Amer.

Journ. of Physiol., 1905, xiii. 192.
A. J. CARLSON. The Nature of Cardiac Inhibition, with special reference to

the Heart of Limulus. Amer. Journ. of Physiol., 1905, xiii. 217.
A. J. CARLSON. Comparative Physiology of the Invertebrate Heart. Part II.

Amer. Journ. of Physiol., 1905, xiii. 396 ; Part III. ibid., 1905, xiv. 16 ;

Part IV. ibid. 1905-6, xv. 127; Parts V., VI., VII., VIII., ibid., 1906, xvi.

47, 67, 85, 100.
"VV. H. HOWELL and W. W. DUKE. Experiments on the Isolated Mammalian Heart

to show the Relation of the Inorganic Salts to the Action of the Accelerator

and Inhibitory .Nerves. Jouru. of Physiol., 1906-7, xxxv. 131.
A. -T. CARLSON. Comparative Physiology of the Invertebrate Heart. Part IX.

Zeitschr. f. allgem. Physiol., 1907, vi. 287.
W. T. PORTER. Studies in the Physiology of Muscle. Observations on the

Tonus of Heart Muscle. Amer. Journ. of Physiol., 1905-6, xv. 1.
T. SOLLMANN. The Revival of the Excised Mammalian Heart by Perfusion with

Oil. Amer. Journ. of Physiol., 1905-6, xv. 121.
A. J. CARLSON. On the Mechanism of Co-ordination and Conduction in the

Heart, with special reference to the Heart of Limulus. Amer. Journ. of

Physiol., 1905-6, xv. 99.
W. H. HOWELL. Vagus Inhibition of the Heart in its Relation to the Inorganic

Salts of the Blood. Amer. Journ. of Physiol., 1905-6, xv. 280.
J. ERLANGER. Further Studies on the Physiology of Heart Block. Amer.

Journ. of Physiol., 1906, xvi. 160.
A. J. CARLSON. On the Chemical Conditions for the Heart Activity, with

special reference to the Heart of Limulus. Amer. Journ. of Physiol., 1906,

xvi. 378.

F. S. LOCKE and 0. ROSENHEIM. Contribution to the Physiology of the Isolated

Heart. The Consumption of Dextrose by Cardiac Muscle. Journ. of
Physiol., 1907-8. xxxvi. 205.

C. C. GUTHRIE and F. H. PIKE. The Relation of the Activity of the Excised

Mammalian Heart to Pressure in the Coronary Vessels and to its Nutrition.

Amer. Journ. of Physiol., 1907, xviii. 14.
H. E. EGGERS. The Rhythm of the Turtle's Sinus Venosus in Isotonic Solutions

of Non-electrolytes. Amer. Journ of Physiol., 1907, xviii. 64.
A. J. CARLSON. On the Mechanism of Refractory Period in the Heart. Amer.

Journ. of Physiol., 1907, xviii. 71.
A. D. HlESCHFELDBK and J. A. E. EYSTER. Extrasystoles in the Mammalian

Heart. Amer. Journ. of Physiol., 1907, xviii. 222.
J. ERLANGER and J. R. BLACKMAN. A Study on Relative Rhythmicity and

Conductivity in various Regions of the Auricles of the Mammalian Heart.

Amer. Journ. of Physiol., 1907, xix. 125.

D. R. HOOKER. May Reflex Cardiac Acceleration occur independently of the
Cardio-inhibitory Centre ? Amer. Journ. of Physiol., 1907, xix. 417.

T. G. BRODIE and W. C. CULLIS. An Apparatus for the Perfusion of the Isolated
Mammalian Heart. Journ. of Physiol., 1908, xxxvii. 337.

G. N. STEWART. Some Observations on the Behaviour of the Automatic
Respiratory and Cardiac Mechanisms after Complete and Partial Isolation
from Extrinsic Nerve Impulses. Amer. Journ. of Physiol., 1907-8, xx.
407.

A. J. CARLSON. The Conductivity produced in the Non-conducting Myocardium

of Limulus by Sodium Chloride in Isotonic Solution. Amer. Journ. of

Physiol., 1908, xxi. 11.
A. J. CARLSON. A Note on the Refractory State of the Non-automatic Heart

Muscle of the Limulus. Amer. Journ. of- Physiol., 1908, xxi. 19.
A. J. CARLSON and W. J. MEEK. On the Mechanism of the Embryonic Heart

Rhythm in Limulus. Amer. Journ. of Physiol., 1908, xxi. 1.
W. H. HOWELL and W. W. DUKE. The Effect of Vagus Inhibition on the

Output of Potassium from the Heart. Amer. Journ. of Physiol., 1908,

xxi. 51.

340 PHYSIOLOGY CHAP, ix

W. J. MEEK. The Relative Resistance of the Heart Ganglia, the Intrinsic Nerve

Plexus, and the Heart Muscle to the Action of Drugs. Amer. Journ. of

Physiol., 1908, xxi. 230.
W. H. SCHULTZ. Studies in Heart Muscle. The Refractory Period and th/

Period of Varying Irritability. Amer. Journ. of Physiol., 1908, xxii. 133.
A. J. CARLSON. Comparative Physiology of the Invertebrate Heart. Part X.

Amer. Journ. of Physiol., 1908, xxii. 353.
H. J. B. FRY. The Influence of the Visceral Nerves upon the Heart in

Cephalopods. Journ. of Physiol., 1909-10, xxxix. 184.
J. ERI.ANGER. Can Functional Union be re-established between the Mammalian

Auricles and Ventricles after Destruction of a Segment of the Auriculo-

Ventricular Bundle? Amer. Journ. of Physiol., 1909, xxiv. 375.

CHAPTEE X

PHYSIOLOGY OF VASCULAK MUSCLE AND NERVES

SUMMARY. — 1. Discovery of vasomotor nerves. 2. Vascular tone and its
rhythmic and a-rhythmical variations, as depending essentially upon the automatic
and reflex excitability of the smooth muscle cells. 3. Theory of vaso-constrictor
nerves. 4. Theory of vaso-dilator nerves. 5. Vascular reflexes. 6. Bulbar vaso-
constrictor centre. 7. Spinal and cerebral centres for vaso-constrictor nerves.
8. Centres for vaso-dilator nerves. Bibliography.

THE preceding chapter on the physiology of cardiac muscle and
the cardiac nerves will facilitate our investigation of the physiology
of the muscle cells and nerves with which the walls of the blood-
vessels are provided. As we shall see, there is an exact analogy
between the physiological phenomena in both cases.

I. After Haller, Spallanzani, Magendie, and Poiseuille had
demonstrated the possibility of the circulation of the blood, in
virtue simply of the heart's activity as a force-pump, and the
physical elasticity of the blood-vessels, the older theories as to the
importance to the circulation of the muscle cells and vascular
nerve fibre were disregarded and almost forgotten. At the
commencement of the last century, however, certain normal and
pathological phenomena, which directly contradicted the purely
mechanical theory, again attracted the attention of physicians
and physiologists. Among these are : abnormal conditions of
temperature and nutrition in paralysed limbs, circulatory changes
(blushes and pallor) due to emotional states or to neuralgia,
hyperaemia, and congestion at the seat of inflammation, pneumonia
after section of the vagi, panophthalmia on dividing the trigeminal,
failure of erection o/ penis, when the spinal nerves have been
divided, and so on.

The precursors of the physiology of the active movements of
the vessels included E. H. Weber (1831), Henle (1840), Stilling
(1840), Valentin and Schiff (1844), who adumbrated not a few of
the facts and theories which subsequently received experimental
confirmation.

In 1851 Claude Bernard discovered and described the
phenomena that occur in the vessels of the rabbit's ear, on

341

342 PHYSIOLOGY CHAP.

division of the cervical sympathetic, after which the notion of
vascular nerves became familiar. Cl. Bernard was more struck
by the marked rise of temperature in all parts supplied by the
sympathetic than by the dilatation of the vessels, so much so
that in 1852 he gave an erroneous interpretation of the same,
declaring the sympathetic to be a thermal nerve. Shortly after-
wards, however, Brown - Se'quard completed the discovery by
describing the converse phenomena that occur in the vessels of
the ear, when the peripheral end of the divided nerve is excited
by an electrical stimulus. This he rightly interpreted as meaning
that the primary effects were dilatation and constriction of the
vessels, the secondary effects, the warming or cooling of the parts
supplied ; and he gave the name of vaso-constrictors to the rami
auriculares of the cervical sympathetic system. A. Waller almost
simultaneously confirmed these same facts and their significance,
without knowing of Brown-Sequard's publication.

In 1854, M. Schiff, observing the vessels of the rabbit's ear by
transmitted light, described an irregular succession of contractions
and dilatations, which are much slower than the rhythm of the
heart, and quite independent of it. Owing to these undulations,
the flow of blood through the ear alternately diminishes and
increases (ischaemia and hyperaemia), with a consequent fall and
rise of its temperature, blood pressure, and volume.

In 1856 he showed indirectly that besides the vaso-constrictors,
vaso-dilators are also present in the cervical sympathetic, so that
the rhythm, which he detected in the vessels of the ear, must be
regarded as the result of the alternate functional predominance
of one or other kind of vasomotor nerve. He found when the
animal was artificially warmed some days after dividing the
cervical sympathetic, or was forced to take violent movements, or
infected with a septic or toxic fever, that the vessels of the ear
on the normal side showed much greater vascular dilatation,
hyperaemia and heating than those on the operated side, a fact
which led Schiff to the conclusion that the former were under
the control of dilator nerves, which in the second case had been
divided.

SchifFs view was brilliantly confirmed in 1858 by Claude
Bernard, who discovered the effect produced in the vessels of the
submaxillary gland of the dog, by electrical stimulation of that
branch of the facial nerve which traverses the tympanic cavity,
joins the lingual branch of the trigeminal, and then under the
name of chorda tympani passes partly into the tongue, partly to
the submaxillary and sublingual glands. That the chorda
tympani contains vaso-dilator fibres is shown by the fact that its
stimulation produces marked hyperaemia of all the vessels of the
submaxillary gland, associated with such marked acceleration of
the blood-stream that the flow through the glands has scarcely

x VASCULAR MUSCLE AND NERVES 343

time to acquire the characteristics of venous blood, while the
pulse wave of the arteries passes beyond the capillaries, and
reaches the small veins (Fig. 155).

There are, accordingly, constrictor and dilator nerves to the
blood-vessels : the former correspond to the systolic, the latter to
the diastolic, nerves of the heart. Vascular rhythm and tonicity
are analogous to cardiac rhythm and tonicity. Just as the
innervation of the heart regulates the circulation as a whole, so
the innervation of the vessels regulates the circulation in the
several vascular regions. The same questions as were examined

FIG. 155.— Operative procedure for exposing submaxillary gland, duct, nerves and vessels.
(Cl. Bernard.) Gsm, Submaxillary gland ; D?c, Wharton'.s duct, into which a glass cannula is
inserted to draw off the saliva secreted by the gland ; Db, Bertholin's duct to sublingual ;
Nl, lingual nerve ; Ct, chorda tympani, running to gland along with excretory duct ; C, carotid
accompanied by small nerve branches of sympathetic ss ; Vje, external .jugular vein ; V,
efferent vein from gland ; Ni, hypoglossal nerve ; Md, anterior half of digastric muscle, lifted
by hook ; Mmj, mylo-hyoid muscle, cut so as to expose the lingual nerve, and excretory ducts
beneath it ; Mn, maseter muscles.

and discussed in studying the active movements of the heart
crop up in the study of the active movements of the vessels.
We must therefore consider separately the rhythm and the tone
of the vessels, the vaso-constrictors, and the vaso-dilators, in the
better-known vascular regions.

II. The slow rhythm of dilatation and constriction, as first
described by Schiff for the vessels of the rabbit's ear, is no isolated
phenomenon. It was observed by Wharton Jones in the vessels ot
the bat's wing, by Saviotti on the frog's peritoneal arteries, by
Riegel in the small mesenteric arteries and web of the same
animal. In this category must also be included the long irregular
waves "of the third order," which are independent of cardiac rhythm
and respiratory movements, and were first noted in blood-pressure

344

PHYSIOLOGY

CHAP.

curves by Traube and Hering. Lastly (1875), Mosso found with
his plethysmograph (Fig. 156) that the volume of the human fore-
arm exhibits the same long and irregular oscillations, which can
only be interpreted as the effects of a peculiar rhythm of alternate
contractions and dilatations of the vessels of the limb. Von Basch

n

FIG. 156.— Mosso's plethysmograph, for recording slow variations in volume of vessels of fore-
arm (diagram). A, B, glass cylinder to receive the forearm, closed by rubber band ; this
rests on the board E, which is suspended from the ceiling by a wire ; C, opening closed with a
cork, through which the cylinder can be filled with lukewarm water ; D, opening through
which a thermometer is passed, showing temperature of water ; F, G, tube through which the
cylinder containing the forearm communicates with the small cylinder M, which floats above
the level of the fluid ft, b, contained in large vessel P ; N, lead weight carrying the pen to write
on moving cylinder of kymograph, which counterpoises M, with which it is connected by two
silk threads passing over the double pulley L ; H, J, burette that can be raised or lowered in
adding or changing the water in the float. The instrument works as follows : when the vessels
of the forearm contract, an amount of water corresponding with the diminution in volume is
aspirated from the float M to the cylinder A, B ; this raises the float and depresses the counter-
poise N, which records the diminution of volume on the revolving cylinder. When, on the con-
trary, the vessels of the forearm dilate, a quantity of water in the cylinder A, 13 is driven out
into M, so that it sinks, and N is raised, recording the increase of volume. To avoid positive
or negative pressure above the forearm immersed in the cylinder A, B, care must be taken
that its upper level is at the same level a, b as the water contained in the receiver P where M
is floating.

(1876) confirmed Mosso's facts with a weighing plethysmograph,
which gives more relative values than Mosso's apparatus. From
all these observations it appears probable that the autochthonous
rhythm of the vessels is common to many other vascular tracts
that have not yet been fully examined (Figs. 157 and 158).

It must not, however, be assumed that rhythmical activity is
continuous and constant in all vascular regions : in most cases,
indeed, the microscopic study of transparent vascular tracts shows

VASCULAR MUSCLE AND NERVES

345

B C

no alteration in the diameters of the vessels, which may remain
for a considerable time in the state intermediate between excessive
dilatation and excessive constriction, which is commonly known as
tonus or tonic contraction of the vessels.

Vascular rhythm, being much slower and less regular, does not
correspond with the functional rhythm of the heart, i.e. with the
alternation of cardiac systole and diastole. On the other hand, it
does correspond, and is in strict analogy, with the tonic rhythm
discovered by Fano in the walls of the tortoise auricle, and results
from the alternate contraction and expansion of the sarcoplasm of
the smooth spindle-shaped muscle cells of the tunica media,
particularly in the small arteries.

The tone and rhythmical activity of the Veins is obscure, and
has been little studied; their
muscular cells are few in number,
and vary considerably in differ-
ent regions and tissues. The
veins of the bones and brain
have no contractile elements ;
the veins of the portal system
are highly muscular It is only
at the extreme ends of the venae
cavae and pulmonary veins,
where they open into the aur-
icles, that, in addition to a
perhaps slowly varying tonus,
we find any rapid and fairly
regular rhythmicalactivity,such
as gives rise to the systolic and
diastolic rhythm of the heart.

The autochthonous activity of the vessels, whether tonic or
rhythmic, resembles that of the heart, in being automatic, i.e.
independent of external stimuli acting on the muscle cells.
This conclusion is reached, not merely by analogy, which in this
instance is of great value, but also by direct observation, from
which every unbiased observer must perceive that the oscillations
of tone in the vessels of the rabbit's ear are independent of
changes in external conditions. It is uncertain whether the
tonic and rhythmic activity of the vessels is, like that of the
heart, an inherent property of the muscle cells, as claimed by
the myogenists, or whether it is brought about by the peripheral
ganglia and nerve fibres which are particularly abundant in the
walls of the arteries, where they form a delicate plexus round
the smooth muscle cells. Experience shows that the neuro-
paralytic hyperaemia and rise of temperature consequent on the
division of all the nerves of the limb does not persist, but dis-
appears gradually, so that after some days the paralysed limb is

FK;. 157.— Tracings obtained with plethysmograph
of Fig. 1.06. (MOSSO.) The revolving drum is
moved on a short distance at each minute, so
that the writing point traces a horizontal line.
The variations in volume that occur during the
minute in which the drum is stationary are
indicated by vertical lines, which show the
extent of the oscillations in volume during that
period. In this case each cm. in height from
the ordinate corresponds to 2 c.c. of blood. At
P, P the subject replied to questions put by
the experimenter. At A he raised his left hand
to rub his nose, at B to rub his ear. At C he
heard the sound of an electric bell.

346

PHYSIOLOGY

CHAP.

more ischaemic and cooler than the healthy limb on the opposite
side (Goltz and others). This means that the muscle cells, or
peripheral ganglionic elements, may, independent of the nerve
centres, acquire a degree of tonic contraction in excess of the
normal. On the other hand we know that even excised organs,
e.g. the dog's kidney, artificially circulated, exhibit with the

FIG. loS. — Plethysmogram of forearm, obtained by connecting the cylinder, A, B, of plethysmo-
graph with a Marey's writing tambour. (Mosso.) - The rotating drum moves at uniform speed.
The experiment was performed in an iron room, where the air could be compressed to various
measurable pressures. Each tracing, in addition to the plethysmograms of the pulse, shows
the slow oscillations in volume of the forearm which depend on the oscillations of vascular
tone. 1, Tracing made before compression of air; 2, at KX) mm. Hg compression; 3, at
100 mm. Hg ; 4, at 80 mm. Hg ; 5, at 50 mm. Hg ; 6, at ordinary barometric pressure ; 7, two
minutes alter return to ordinary barometric pressure ; 8, a quarter of an hour later.

plethysniographic method constant irregular oscillations of
volume, which obviously depend on oscillations of tone in the
renal vessels (Mosso, 1874).

A similar effect was noted by Bernstein in the amputated
paw of the dog. So, too, the work of Bayliss (1901), on the
reaction of certain blood-vessels to changes of blood pressure,
shows that the vascular muscles are capable of altering their
tone independent of the nervous system. Bayliss found on
recording the changes in volume of the hind limb of an animal,

x VASCULAK MUSCLE AND NERVES 347

completely separated from the central nervous system by the
plethysmograph, that artificial depression of blood pressure-
caused by compression of the abdominal aorta, or by stimulating
the peripheral trunk of the vagus, or depressor nerve — produced
an initial shrinkage of volume. Even during the fall of blood
pressure, however, there was a gradual return to the earlier
volume, while after normal pressure was restored there was a
marked increase in volume, a proof that the vessels reacted to
the fall of blood pressure by a definite dilatation. Artificial
rise of blood pressure (e.g. from stimulation of the splanchnic)
produced constriction of the vessels of the limb.

The muscular coat of the vessels (like the muscular wall of
the heart) is automatically active both in constriction and in
dilatation — the former caused by the shortening, the latter by
the lengthening or expansion of the sarcoplasm of the spindle-
shaped muscle cells. This hypothesis, which found little favour
when we propounded it in 1871-73, as the logical deduction
from Weber's theory of muscular elasticity, is now, on the
strength of recent work on the automatic rhythmicity of the
cardiac muscle cells (that of Gaskell and Engelmann in particular),
not only unopposed, but even included, in many modern text-
books. " We have repeatedly insisted " (says Foster l) " that the
relaxation of a muscular fibre is as much a complex vital
process, is as truly the result of the metabolism of the muscular
substance, as the contraction itself ; and there is a priori no reason
why a nervous impulse should not govern the former as it does
the latter."

Vascular tonicity and its slow rhythmical oscillations (Fig.
158) are probably inherent properties of the smooth muscle
cells and the vascular nerves that direct and regulate them,
since they exert a double and opposite influence, katabolic and
anabolic, upon the metabolism of muscle. The vaso-constrictors
function by promoting the dissimilatory processes; the vaso-
dilators, on the contrary, by favouring the assimilatory processes
of cellular sarcoplasm. The first are therefore katabolic, the
second anabolic nerves to the vessels. The active movements of
the vessels are thus regulated by mechanisms perfectly analogous
to those which govern the active movements of the heart.

III. It is known, on the strength of numerous experiments,
that every vascular region is supplied with vaso-constrictor nerves.
This is plain on recapitulating the most important heads of the
copious literature of the subject.

The great splanchnic nerve contains numerous constrictor
fibres which supply the most extended area, since it controls the
blood-vessels of the greater portion of the abdominal viscera.
Ludwig and Cyon (1866), v. Bezold and Bever (1867), found

1 Text-Book of Physiology, Part I. p. 313, 5th ed., 1888.

348 PHYSIOLOGY CHAP.

that division of this nerve produced a marked fall of lateral
pressure in the aorta, while stimulation of the peripheral end
of the divided nerve raised the pressure above that which
obtained before section. On investigating the state of the
visceral vessels after section, marked congestion was observed
in the venous portal system, with distinct hyperaemia of the
small vessels of the mesentery, intestinal canal, and renal
parenchyma. These effects are more pronounced in the rabbit
than in the dog (Asp), apparently because in herbivores the
gastric canal is much longer than in carnivores.

The constrictor fibres of the splanchnic run to the coeliac
plexus, and thence to the stomach, intestines, and kidneys.
Excitation of the splanchnic on one side only causes the vessels
of both kidneys to contract (Cohnheim and Boy).

The constrictor fibres of the hepatic vessels also emerge from
the splanchnic, and pass to the coeliac plexus, and thence to the
liver, along the bile-duct and hepatic artery (Vulpian). The
vaso-constrictors of the spleen come from the left splanchnic,
and perhaps also from the right (Roy).

It is known from other observations that the great splanchnic
does not contain all the vaso-constrictor fibres of the abdominal
viscera. The lesser splanchnic has fibres of the same character
(Asp), and the abdominal branches of the vagus also appear to
contain vaso-constrictors for the spleen (Oehl).

Next to the great splanchnic, the vaso-constrictor nerve
which supplies the most extended tract is certainly the cervical
sympathetic, which not only regulates tonicity in the vessels of
the ear, as discovered by Claude Bernard, but also exerts its
constrictor function on all other external and internal vessels of
the head, as appears from the investigations of several observers.

It was plain from the work of Budge and Waller (1853) that
the constrictor fibres of the cervical sympathetic did not arise in
the ganglia situated along its course, but in the anterior roots of
the spinal nerves, whence they emerged by the raini communi-
cantes. The constrictor fibres run principally with the vessels
round which they form a plexus ; but they are partly associated
with the cerebral nerves, leaving them again later, to join the
vessels. Thus the hypoglossal and lingual branches of the
trigeminal contain vaso-constrictor fibres for the tongue (Vulpian).
The facial nerve, again, contains many fibres of the same kind, so
that division of this nerve is followed by a rise of temperature in
the whole face (CL Bernard). These vaso-constrictor fibres do
not originate in the centres of the cerebral nerves, seeing that
destruction of these centres produces no sign of vascular paralysis.
They probably emerge from the sympathetic.

It is, however, possible that besides the constrictor fibres from
the sympathetic, the vessels of the head are affected by other

x VASCULAK MUSCLE AND NERVES 349

constrictor fibres, the origin of which is not yet determined.
Thus, e.g., the vessels of the ear also receive constrictors from the
second and third nerves of the cervical plexus (Schiff, Loven, etc.).

The vaso-constrictors of the limbs run principally to the
cutaneous vessels, the vessels of the muscles being less well
supplied with motor nerves (Sadler, Hafiz, Grtitzner and Heiden-
hain, and others).

The vaso-constrictors of the fore-limbs originate in the anterior
roots of the median tract of the thoracic cord (third to seventh
nerves), join the sympathetic, and unite at the first thoracic
ganglion with the ramifications of the brachial plexus. The
cervical roots which contribute to the formation of this plexus
contain no vaso-cons trie tor fibres (01. Bernard, Cyon, etc.). Some
of these fibres accompany the vessels of the limb directly, without
joining the branches of the brachial plexus (Vulpian).

The vaso-constrictors of the lower limbs have been more
studied. They emerge, not from the roots of the lower segment of
the cord, but from the thoracic tract and upper segment of the
lumbar cord, particularly from the eleventh, twelfth, and thirteenth
dorsal, and the first and second lumbar nerves (Bayliss and
Bradford). They pass by the rami communicant es to the thoracic
and abdominal sympathetic, then, for the most part, joining the
great nerve trunks to the limbs, the sciatic especially ; while a few
only accompany the vessels of the limbs direct from the abdominal
ganglia.

It is clear from the consensus of observations on the vaso-
constrictors in different regions that they originate principally in
the anterior roots of the dorsal tract of the cord, pass by way of
the rami communicantes to the ganglion sympathetic system, and
thence run directly or indirectly to the vessels, where they form a
fine plexus round the muscular tunica media. Their excitability
is less, and their latent period longer than that of the motor nerves
to the skeletal muscles, and they are constantly in a certain state
of activity, on which the tone of the vessels depends. Section of
these nerves accordingly produces vascular atony and subsequent
hyperaemia, while excitation of the peripheral cord produces
constriction or vascular hypertonia and subsequent ischaemia.

What modifications in local blood pressure and velocity of
circulation are produced by such hyperaemia or ischaemia ? Little
was known definitely before Dastre and Morat published their
observations on the horse. They employed two sphygmoscopes,
one applied to the facial artery, the other to the facial vein of the
animal. They found that Hgation or section of the cervical
sympathetic caused a fall of blood pressure in the artery, and a
rise in the vein (local circulatory delay). Stimulation of the nerve,
on the contrary, produced rise of arterial and fall of venous
pressure (local acceleration of circulation), folio wed by the contrary

350 PHYSIOLOGY

CHAP.

phenomenon, viz. fall of arterial and rise of venous pressure,
greater than that which occurs on simple division of the nerve
(local circulatory delay) in consequence of fatigue (Fig. 159).

The fact of vascular ultra-dilatation is very interesting, as it
implies that strong and persistent excitation of the nerve exhausts
the peripheral ganglia, and thus depresses the tone which these
maintain in the vessels even after the nerve has been divided.

IV. Since 1874, the theory of vaso- dilator nerves has been
much developed. Next to Bernard's discovery of the vaso-
dilator fibres contained in the chorda tynipani (referred to
above), the discovery of the nervi erigentes of the penis by
Eckhardt (1863) demands special mention. These nerves are

FIG. 159. — Effect on arterial and venous pressure in facial vessels of electrically exciting the
peripheral trunk of horse's cervical sympathetic. (Dastre and Morat.) Af, tracing of blood
pressure in peripheral trunk of facial artery ; Vft of facial vein. The excitation took place at
the part between the two vertical lines, marked on abscissa by an electric signal separate from
that which shows the time in seconds. The tracings show tnat stimulation of the sympathetic
is followed by a rise of arterial and fall of venous pressure (preceded by temporary rise due
to increased outflow), which is succeeded by the opposite effect, i.e. fall of arterial, and rise
of venous pressure, due to extra-dilatation of vessels.

branches from the sacral plexus, which, when peripherally stimu-
lated, cause erectile swelling of the corpora cavernosa, due not
to obstruction of the venous outflow, but to increased arterial
influx, owing to active dilatation of the helicine arteries. These
two discoveries, however, remained isolated for more than a decade,
and Goltz (1874) was the first to suggest that the dilators, like
the constrictors, were distributed to every vascular region, the
difficulty of experimental proof arising from the fact that they
nearly always run jointly with the constrictor fibres, which by
their prevailing influence on the tone of the vessels mask the
antagonistic action of the dilators.

For this reason it cannot be decided 'whether the dilator nerves
are, like the constrictors, in tonic activity ; section of the chorda
tynipani or nervi erigentes produced no perceptible constriction of
the vessels to which they are distributed.

x VASCULAR MUSCLE AND NERVES 351

There has been much discussion as to whether the sciatic trunk
contains vaso- dilator fibres. Goltz and others noted, as the
primary effect of dividing the nerve, the atonic dilatation of the
vessels in the limb, exhibited principally in the increased
temperature of the paw ; while the primary effect of peripheral
stimulation is vascular constriction, shown chiefly in the cooling of
the same — as also by increased blood pressure in the small arteries
of large animals (Fig. 160). Shortly after the section of the
sciatic, however, the paralysed limb cools off gradually, till at the
end of a few days it is colder than the healthy leg, probably because
the peripheral ganglia are capable, even when separated from the
spinal centres, of recovering their vascular tone until it exceeds
the normal. If, when this effect has been produced, the divided

Fio. 160. — Effect upon smallest arteries of posterior extremity of exciting peripheral trunk of left
sciatic in horse. (Morat.) A,f, d, pressure in central trunk of right femoral artery ; A,f, s,
pressure in peripheral trunk of left femoral artery. Two electric signals record the time
in seconds, and the duration of excitation by a tetanising current on the abscissa. Shows
that the constriction of the small arteries of a posterior limb hardly increases the central
pressure in the femoral of the other limb, while the peripheral pressure in the femoral
of the same side, which anastomoses with the small contracting arteries, is conspicuously
increased.

sciatic is again exposed and excited mechanically at the peripheral
end, the temperature of the paw rises considerably and exceeds
that of the normal side. This shows the presence of dilator fibres
in the sciatic, which retain their excitability for a longer time
after section than the vaso-constrictors. These results of Goltz
were essentially confirmed by the subsequent observations of
Ostroumoff, Heidenhain and Griitzner, Kendall and Luchsinger,
and others.

In 1876 v. Frey in Ludwig's laboratory took up Cl. Bernard's
studies on the vascular nerves of the subniaxillary gland, and
determined the amount of blood which flows out of the chief vein
of the glands in the time-unit, when the dilators in the chorda
tympani, or the constrictors of the carotid branches of the
sympathetic, are separately stimulated; or, lastly, when both
kinds of nerves are excited simultaneously. The separate stimu-
lation of the two nerves showed that the dilators have a much

352

PHYSIOLOGY

CHAP.

longer after-effect, and are more quickly tired than the constrictors.
Simultaneous stimulation showed the functional predominance of
the constrictors over the dilators, of which, however, the excitation
is manifested by an after-effect — in agreement with Baxt's
experiments on the cardiac nerves. When, on the contrary, the
constrictors are stimulated with a weak, and the dilators with a
strong, current, the latter predominate.

Certain experiments of Lepine, and later on of Bernstein,

FIG. 161.— Plethysmograrn.s of hind-limb of cat during electrical excitation of divided sciatic,
by induction shocks of varying frequency. (Bowditch and Warren.) The sciatic was excited
in the intervals comprised between the two vertical lines = 15". At A, with 1 shock at each
second, a slight vascular contraction, followed by marked dilatation, was obtained. At B, with
4 shocks at each second, the contraction was larger, with a larger succeeding vascular
dilatation. At C, with 16 shocks per second, there was marked contraction with very small
dilatation. At D, with 64 shocks per second, there was a very marked contraction, with no
subsequent vascular dilatation.

indicate that the atonic or hypertonic state of the vessels previous
to electrical excitation of their respective nerves leads to the
preponderance of the constrictors over the dilators, and vice versa.
They found, namely, that the stimulation of the sciatic produced
constriction or dilatation of the vessels, according as the extremities
had previously been warmed or cooled with hot or cold water.

Ostroumoff further showed that a different rhythm, or a
varying intensity of electrical excitation, led to the predominance

x VASCULAK MUSCLE AND NERVES 353

of one or other kind of vascular nerve. The dilators are more
readily excitable to currents of slow rhythm or low intensity ;
the constrictors, on the other hand, to tetanising currents, i.e.
currents of high frequency, or great intensity. These results
were strikingly developed and confirmed in the experiments of
Bowditch and Warren on the cat by the plethysmograph method,
in which the oscillations of volume in the hind -limbs were
recorded during the excitation of the sciatic by currents of high
or low frequency and intensity. The plethysniograms of Figs. 161
and 162 are so plain as to need no description.

On the other hand, Piotrowski was unable on the dog to obtain
the same results as Bowditch and Warren. On stimulating the
sciatic with varying frequencies, he constantly observed a diminu-
tion and never an increase in the volume of the limb.

The two kinds of vascular nerves, which run together in the
peripheral nervous system, may take a separate course at a higher
point and leave the cord at different places. This was shown by

Fiu. 162. — Plethysmograms of hind-limb of cat during electrical excitation of divided sciatic, by
induction shocks of equal frequency (1 per second), and equal duration (20"), but of varying
strength. (Bowditch and Warren.) At A, with strength of shock = 100, primary dilatation of
vessels of limb; at B, with strength of shock = 150, more pronounced dilatation preceded by
temporary contraction; at C, with strength of shock ^200, still more marked dilatation,
preceded by greater vascular constriction.

Dastre and Morat, who, on exciting the thoracic sympathetic
immediately above the diaphragm, constantly obtained dilatation
of the vessels in the lower limbs, while on exciting the abdominal
sympathetic or sciatic they were constricted.

Yet more interesting is another, fact discovered by the same
authors, which plainly shows that the two kinds of vascular nerves,
running in a single nerve trunk, may supply quite distinct regions
at the periphery. On repeating the stimulation of the cervical
sympathetic (which forms with the vagus a single trunk, known as
the vago-sympathetic) on a curarised dog, they observed blanching
in the skin of the ear and mucosa of the tongue, epiglottis, tonsils,
and soft palate on the side excited, with the simultaneous flushing
of the mucosa of the lips, gums, cheeks, hard palate, and nasal
mucosa on the same side. The effect is particularly striking on
comparison with the other side, and -on contrasting the ischaemic
and hyperaemic parts. At the close of excitation the differences
gradually disappear, until the several parts regain their normal
colouring. The entire effect is due to the sympathetic alone, and
not to the vagus, since it appears when the sympathetic is excited

VOL. I 2 A

354 PHYSIOLOGY CHAP.

above or below its union with the vagus, or when the latter has
been divided above the point of junction.

It thus appears that while the vaso-dilators almost always run
with the vaso-constrictors, their presence in the several nerve- trunks
can be detected, either by the physiologically distinct character of
their activity, or by their different course, their central origin,
and their morphologically distinct peripheral distribution.

The data at present before us in regard to the course and
central origin of the vaso-dilators to the different regions are less
complete than those relating to the vaso-constrictors.

The dilators contained in the cervical sympathetic were traced
by Dastre and Morat into the two branches of the Annulus of
Vieussens, the rami communicantes to the second to fifth spinal
nerves, and the anterior roots of the same. The majority unite on
their way to the periphery with the trigeniinal, by an anastomosis
between the superior cervical and Gasserian ganglions. For after
section of the first branch of the trigeniinal in the pterygoid-
inaxillary groove, the vascular dilatation resulting from, stimulation
of the cervical sympathetic appears only to a minimal degree in
the regions above indicated. On the other hand, with excitation
of the trigeminal, after division and degeneration of the cervical
sympathetic, dilatation of the facial vessels is obtained. This
shows that the dilator fibres of this nerve cannot all emerge by
the sympathetic and be of spinal origin ; others accompany the
trigeminus from its roots and are cerebral in origin. According
to Carlson (1907) the cervical sympathetic carries both vaso-
dilators and vaso-constrictors to the cat's submaxillary gland.
This fact had been overlooked by preceding investigators (Heiden-
hain, Langley, Bayliss), who speak only of vaso-constrictor fibres to
the salivary gland in the cervical sympathetic. This is due to
their observations having been made upon the dog (and other
mammals), in which the constrictors probably preponderate in the
cervical sympathetic, so that on stimulating the nerve the
constrictor effect alone is apparent.

According to Langley, the dilators of the fore-limb originate in
the thoracic nerves (5th-8th pairs). The greater proportion of the
dilators to the hind-limbs run in the sciatic, a very few in the
crural. The work of Ostrournoff and others shows that these do
not arise in the sacral, but in the lumbar roots (2nd-4th pairs),
passing thence by the rami communicantes to the abdominal
sympathetic (and in a minority to the thoracic sympathetic) before
they unite with the sciatic. According to the observations of
Strieker, subsequently confirmed by Cossy, Vulpian, and others,
they do not arise like all other motor nerves in the anterior roots
alone, but also in the posterior roots of the fourth to fifth lumbar
pairs. This is the only well-proved exception to Bell's law (see
vol. iii.).

x VASCULAR MUSCLE AND NERVES 355

The recent work of Bayliss (1901) on the origin of the vaso-
dilator nerves has confirmed and completed Strieker's observations,
although it is partly contradictory of the conclusions just
enumerated. Electrical, chemical, thermal, and above all mechanical
stimulation of the peripheral trunk of the divided posterior roots
of the fifth, sixth, and seventh lumbar, and the first sacral nerves,
determine on the dog a pronounced vaso-dilatation of the hind-
limb. A similar dilatation of the fore-limb is exhibited on
stimulating the posterior roots of the sixth, seventh, and eighth
cervical and first thoracic nerves. The dilator fibres of the hind-
limbs do not run with the abdominal sympathetic, but enter the
lumbo-sacral plexus direct. They degenerate after extirpation of
the spinal ganglia, but do not degenerate when the posterior roots
are cut between the cord and the spinal ganglia. They thus
behave in a manner perfectly analogous to all other nerve-fibres
emerging from the posterior roots, which have their trophic centres
in the spinal ganglia. Lastly, it has not been demonstrated that
the hind-limbs receive any vaso-dilator fibres other than those
which run in the posterior spinal roots.

Till quite recently little was known of the dilator fibres to the
visceral vessels. Bradford, on methodically stimulating the several
pairs of spinal nerves with low frequency currents, found that the
eleventh, twelfth, and thirteenth dorsal pairs at least, in addition
to the constrictor fibres, contain numerous dilator fibres to the
renal vessels, these being, on the contrary, very few in the other
dorsal pairs, and altogether absent in the lumbar pairs. On
experimenting by the same method with the splanchnic, the most
important of the vaso-constrictor nerves, he found that it also
contains vaso-dilator fibres, which probably serve the intestines.

After Eckhard's discovery of the nervi erigentes (1863) they
were at a later period studied by Gaskell (1887) and Morat (1890),
with the object more particularly of determining their origin. It
was found that stimulation of the anterior roots of the second and
third sacral nerves in rabbit, and first and second sacral nerves in
the dog, caused almost as pronounced an erection of the penis
as the stimulation of the nervi erigentes. Stimulation of the
posterior roots never produces the slightest trace of erection.

These are the most important experimental data in regard to
the origin and course of the vaso- dilators.

V. The vascular nerves, like the cardiac nerves, are capable of
reflex excitation, i.e. they can be stimulated by the afferent nerves
to the centres. As in the heart there are afferent nerves which
act reflexly upon the heart itself, -so in the vessels we must
assume the existence of afferent nerves, capable of acting reflexly
on the vessels. This was first demonstrated by Heger (1887). In
the curarised dog or rabbit he injected nicotine or silver nitrate,
peripherally, by the crural artery, and simultaneously recorded the

356 PHYSIOLOGY CHAP.

lateral pressure of the aorta after ligaturing the crural vein.
Directly after the injection he observed either an instantaneous
fall of blood pressure, or a fall preceded by a rise. Heger referred
this reflex phenomenon to the action of the capillary walls, since
neither pressor nor depressor effects appeared, when the injected
substance was localised in the artery or vein. The reflex also
occurs when the hind-limb is only connected by the sciatic to the
rest of the body.

Spallitta and Consiglio, in Marcacci's laboratory, extended and
completed the observations of Heger. According to the Italian
workers, excitation of the sensory nerves to the internal surface
of the blood-vessels, by chemical agents, constantly produces not
merely rise of blood pressure, but also slowing of heart-beat with
increased amplitude of pulse. Since excitation of the sensory
nerves of the heart, or, according to the latest researches, of the
aorta, produces a depressor effect, antagonistic, i.e. to that of the
afferent nerves to the peripheral vessels, it seems logical to conclude
that under normal conditions also the two kinds of sensory nerves
exert an opposite action on the circulation. The sensory nerves of
the heart or aorta prevent undue filling or overloading of the
heart ; the sensory nerves of the peripheral vessels obviate undue
filling and distension of the vessels.

Since it is proved that vascular reflexes may be excited by
afferent fibres in the walls of the vessels themselves, it is probable
that they play a part in the physiological regulation of blood
pressure. On the other hand, the tone of the vessels can be
reflexly influenced by any centripetal nerve. Localised vascular
reflexes usually cause the vessels to widen, but at other times
they are first narrowed, and subsequently, as an after-effect,
become wider. This means that the stimulation of the afferent
nerves is transmitted either by the vaso-dilators, or by the vaso-
constrictors, or lastly, by both kinds of nerves. The inconstant or
totally negative results of a number of experiments find their
probable explanation in the partial or total inhibition of the effect.
Only a few examples can here be cited.

If the nerves of taste are excited by sapid substances, there is
not only a reflex secretion of saliva, but also a marked dilatation
of the vessels innervated by the chorda tympani (Claude Bernard).
Central excitation of the posterior auricular nerve usually produces
dilatation of the vessels of the rabbit's ear ; often, however, this is
preceded or followed by vaso-constriction (Snellen and Loven).
On stimulating the nerve in the dorsuni of the dog's paw, dilata-
tion of the saphenous artery is obtained; on exciting the infra-
orbital, or mental (labial) nerve, there is dilatation of the external
maxillary artery (Loven). Central excitation of the sciatic,
the vagus, or the posterior spinal roots, usually produces
reflex constriction of the kidney vessels ; on the other hand,

x VASCULAK MUSCLE AND NERVES 357

dilatation of the same vessels is obtained when the posterior roots
of the eleventh and twelfth dorsal nerves are stimulated, because
in that case the excitation is conveyed by the anterior roots of
the same, which, as we have seen, contain dilator fibres (Bradford).

The vascular reflexes may extend from one side to the other of
the body. On central excitation of the sciatic, the paw on the
opposite side becomes warmer (Masius and Yanlair) ; stimulation
of the nasal mucosa dilates the vessels of the whole head, but more
decidedly on the excited side (Fram;ois-Franck).

The vascular reflexes in man have also been investigated.
When one hand is dipped into cold water, the vessels of the other
hand contract (Brown-Sequard). On electrical excitation of one
limb the vessels of the opposite side contract (Maragliano).

FIG. 1 63. — Plethysmograms of hand (M) and foot (P) recorded from healthy subject in re-
cumbent and motionless posture. (Fano.) The abscissa S, traced with a Deprex signal, in-
dicates at E the moment of electrical excitation of the skin. The line D is traced by a
tuning-fork vibrating at 10 vibrations per second.

Fano has also experimented on the vascular reflexes of man,
using an air plethysmograph, by which he was able to record
simultaneously the pulse and the changes in volume of the hand
and foot. He came to the following conclusions : the reaction
time of the vessels is always very long ; it oscillates between two
and seven seconds, according to the conditions in which .the subject
of the experiment is placed, and the part of the body stimulated.
The vascular constriction consequent on a stimulus is always more
pronounced in sleep than in waking. The reaction time is longer
in sleep than in waking. The reaction always occurs, inde-
pendent of the point of stimulation, first in the upper and then
in the lower extremities. In the latter, however, the constriction
is more persistent (Fig. 163).

358

PHYSIOLOGY

CHAP.

Patrizi instituted numerous plethysmographic researches with
the object of determining the exact vasomotor reflex tissues in the
arms, legs, and brain of man, when awake, when asleep, and undei"
various other conditions. Besides confirming certain general laws
for reflexes, in the vascular regions, Patrizi found that the vascular
reflex times, which are fairly equal in the waking state, for the arms
and legs, with a slight advantage on the side of the upper limbs,
undergo in the latter a considerable delay in sleep, whereas the reflex
time for the lower limbs remains constant. During sleep the
reflexes are most delayed in the cerebral vessels.

Patrizi and Cavani also detected a right- and left-handed

FIG. 164. — Reflex pressure effect on excitation of rabbit's skin at E. (Tigerstedt.) Carotid con-
nected with Ludwig's kymograph. Time tracing from an electric signal, along the abscissa,
in seconds.

vasomotor asymmetry in man, to which they attributed a more
rapid and pronounced vasomotor reaction, in one as against the
other half of the body.

This superiority of vasomotor functions usually obtains in that
half of the body which shows itself most capable of muscular force.
The time gained in the vascular reflexes in the favoured half of
the body may amount almost to one second.

In all probability the vasomotor asymmetry is due to the
greater permeability of the nerve paths in the better exercised limb,
which does not exclude the possible influence of the varying
sensory excitability in the two halves of the body, and in the two
corresponding sides of the brain.

These reflexes not infrequently occur in the vascular regions

x VASCULAR MUSCLE AND NERVES 359

most remote from the afferent nerves stimulated. The visceral
vessels innervated by the splanchnic readily respond to the reflex
action of any sensory nerve, for the most part by contracting,
sometimes by dilating, Stimulation of the sciatic also constricts
the vessels of the tongue (Vulpian) ; excitation of the brachial
nerve dilates the vessels of the ear (Loven). This last effect may
be seen on the rabbit, whatever the sensory nerve stimulated, but
the dilatation is usually preceded by vaso-constriction (Eckhard).
• When the vascular reflexes are not confined to any circum-
scribed area, but extend to a wider region, they cause a general

FIG. 165.— Reflex lowering of arterial pressure, from electrical excitation of depressor
nerve of rabbit, in period comprised between two vertical lines. (Tigerstedt.)

modification in blood pressure, usually expressed in an abnormal
rise, sometimes in a fall of pressure.

The reflex pressor effects of exciting the sensory nerves, already
noted by Magendie, were clearly worked out for the first time by
von Bezold (1863), and were subsequently extended by a number
of other experimenters.

They follow particularly on the stimulation of the posterior
spinal roots, the vagus, the trigeminus, the sciatic, the greater and
lesser splanchnic, the cutaneous and muscular nerves, the nerves of
the special senses (Fig. 164). The rise of blood pressure varies with
the nerve excited, and also with the intensity and nature of the
stimulus. The state of the animal prior to stimulation also has
great influence on the intensity of the pressor effect. In the
normal animal, e.g., acoustic stimuli induce a considerable rise of

360

PHYSIOLOGY

CHAP.

arterial pressure, which varies with the pitch, strength, and timbre
of the sound, whereas in curarised animals the rise is hardly
perceptible (Dogiel). Lastly, both the number of sensory nerves,
and the extent of the area stimulated, have great influence on the
degree of pressor effect. For instance, on exciting a limited area
of the skin with strong chemical stimuli, with boiling water, or
red-hot iron, little or no rise of pressure is obtained ; on the other
hand, slight contact, tickling, or blowing of extended areas of the
skin, raises the arterial pressure to nearly double the normal
(Heidenhain and Griitzner).

We saw in the preceding chapter that the central excitation of
the depressor nerves of Ludwig and Cyon invariably produces a

Fir.. 106.— Reflex lowering of arterial pressure of rabbit, from electrical excitation of
centripetal muscular nerve, in period comprised by vertical lines. (Tigerstedt.)

marked reflex fall of arterial pressure (Fig. 165). The afferent
nerves to the muscles also constantly produce a similar effect on
blood pressure (Fig. 166).

Few other afferent nerves are capable of producing reflex
depressor effects. The glosso-pharyngeal usually, but not invariably,
lowers blood pressure (Knoll). With mechanical stimulation of
the rectal and vaginal rnucosa, especially on touching the anus
and vaginal orifice, a primary fall of aortic pressure may be
observed on the curarised dog (Belfield). But if the stimulation
of the inucosa is pushed to deeper parts, the depression is less,
and may even be replaced by a pressor effect. Mechanical stimula-
tion of the skeletal muscles, again, may produce a depressor effect
(Kleen).

We saw that the fall of arterial pressure consequent on excita-
tion of the depressors is due principally to the vaso-dilator fibres

x VASCULAK MUSCLE AND NEKVES 361

of the splanchnic nerve, partly to other dilator nerves, since, when
the splanchnics are divided, the depressor part is not entirely
abolished. It has, however, been established that the depressors
do not exert their reflex dilator action upon all the vascular regions,
and that the vessels of the ear, face, adjacent mucosae, and perhaps
of the skin in general, are constricted during stimulation of the
depressors (Dastre and Morat).

The reflex pressor effects on excitation of the sensory nerves are
chiefly due to the vaso-constrictor fibres of the splanchnics, because
when these nerves are divided, they are much reduced. But even
in these cases vaso-constriction is not the only reflex effect, since
it can be shown that while the internal visceral vessels contract,
the cutaneous vessels dilate. This fact, which indicates a certain
antagonism between the deep and the superficial vessels of the
body, was demonstrated by Heidenhain in measurements of the
temperature of the skin and of the deep-lying portions of the body
during excitation of the sensory nerves.

The antagonism between the cutaneous and visceral vessels
is even more apparent in the asphyxia produced by suspension of
artificial respiration in curarised animals. While the cutaneous
vessels of ear, face, and extremities dilate, those of the viscera
(intestine, spleen, kidneys, uterus) contract. The pressure effect
results from the predominance of vaso-constriction in the visceral
vessels over dilatation of the superficial vessels (Dastre and Morat).
It is highly probable, although definite experimental evidence
is wanting, that this dilatation is active, and not the passive effect
of the constriction of the deep vessels.

We must not, however, take this supposed antagonism between
the deep and the superficial vessels in too absolute a sense, since
the fact that in vascular reflexes constriction of the one and
dilatation of the other occurs is not constant. Heidenhain,
indeed, observed with strong electrical excitation of the medulla
oblongata that there was a pressor effect greater than that of
asphyxia or any kind of reflex stimulation, which was determined
not merely by constriction of the internal vessels, but by that of
the cutaneous and muscular vessels also.

VI. The vascular reflexes, i.e. the excitatory processes trans-
mitted from the centripetal or afferent to the centrifugal or
efferent nerves (the constrictors or dilators of the vessels), are
necessarily carried out by means of the centres in the cerebro-
spinal system, from which the vascular nerves arise. The capacity
of the peripheral ganglia of the sympathetic system to function
as centres for reflex processes (in so far as reflex is taken in
the restricted sense of a transformation of afferent into efferent
influences) has not yet been demonstrated, even if it cannot be
a priori excluded.

We have seen that the greater part, if not the whole, of the

362 PHYSIOLOGY CHAP.

vaso-constrictor fibres arise from the anterior roots of the nerves
in the median or thoracic section of the cord, which is therefore
the principal seat of the apparent origin of these fibres. Next
arises the question as to the centres, i.e. the real origins of the
same. Other special questions are associated with these. Is
there in the central nervous system one single vasomotor centre,
or are there several centres ? If several, are they unified in their
functions, and associated so as to form one single system, or can
they function independently one of another? Are there con-
trolling centres of general circulation on which the tone of the
whole vascular system depends, and controlling centres of local
circulation, on which the vascular tone of this or that organ or
tissue depends ? Generally speaking, it must be admitted that we
are not yet in a position to give a clear and exhaustive answer
to these different questions, particularly to that of the precise
localisation of the vascular centres. We must confine ourselves
to the more fundamental and better established data, and to
drawing from these such conclusions as are legitimate in the
present state of our knowledge.

As early as 1855, shortly after the discovery of the vaso-
constrictors, M. Schiff suggested, in view of the effects of
transversely dividing the cord at different heights, that these
nerves might have their centre in the bulb or medulla oblongata.
In 1859 Cl. Bernard observed a considerable fall in blood pressure
after division of the cervical cord, but he did not pursue the
subject, and von Bezold next took it up in 1863. He found in
curarised animals that stimulation of the cervical cord produced
such an increase in arterial pressure that it becomes seven times
greater than it was immediately after section of the cord. This
marked rise of pressure, which was associated with a pronounced
acceleration of cardiac rhythm, was referred by him to increased
activity of the heart, without taking into consideration the inter-
vention of vascular nerves.

A year after the publication of von Bezold's theory, Ludwig
and Thiry showed it to be erroneous, emphasising the fact that
during excitation of the cervical cord the small arteries throughout
almost the entire body are constricted, which causes the pressor
effect. For, on exciting the cervical cord, a maximal rise of aortic
pressure is obtained, even after the whole of the cardiac nerves
have been divided. The fall after section is therefore the effect
of paralytic atony of the vessels; the rise of pressure during
excitation is the effect of vascular hypertony ; there must therefore
exist in the bulb, i.e. above the divided and excited cord, a vaso-
constrictor centre, which exerts a constant tonic action upon all
the small arteries.

Contemporaneously with Ludwig and Thiry, Goltz, by certain
experiments on the frog, showed the importance of vascular tone

x VASCULAR MUSCLE AND NERVES 363

to the circulation. After destruction of the central nervous
system, there is a marked dilatation of the visceral vessels,
particularly of the veins, in consequence of which nearly the
whole of the blood collects in those vessels, while the remaining
parts of the body are much impoverished. On exposing the
beating heart, he saw that it was almost bloodless, since very little
blood reached it during diastole, and therefore very little could be
expelled into the aorta during systole. It follows that vascular
tonicity is an indispensable condition of the circulation, and that
not merely the arteries, but the veins as well, possess a tone that is
dependent on the central nervous system in general.

The bulbar centre for the vaso-constrictors was more exactly
localised and determined in the subsequent investigations of
Owsjannikow (1871) and Dittmar (1873), in Ludwig's laboratory.
Starting from the fact that central excitation of the sciatic in
curarised dogs and rabbits, even after separation of spinal bulb
from brain by a transverse section, reflexly produces a perceptible
increase in arterial blood-pressure, they endeavoured to define the
region of the bulb in which this reflex occurred. With this
object Owsjannikow made successive cross-sections from above
downwards at different heights of the medulla, and examined both
the depressor effect of each section, and the reflex pressor effect on
exciting the sciatic. The upper limit of the vascular centre lies
at the level of that section after which . there is a fall in aortic
pressure, and a diminution in the height of the reflex rise of
pressure; the lower limit is at that section after which aortic
pressure reaches its minimum, and no longer rises on excitation
of the sciatic. By pursuing this method, with the guidance of
the above data, he decided that the bulbar vasomotor centre in
the rabbit is about 4 mm. high ; its upper limit is 1-2 mm. below
the corpora quadrigemina, its lower limit 4 mm. above the point
of the calamus scriptorius. Since longitudinal section of the bulb
in the median line produces no perceptible fall in aortic pressure,
he concludes that the centre is not in the median line, but consists
of two centres situated at either side of the bulb.

Dittmar, who practically confirmed the results of Owsjannikow
in regard to the longitudinal extension of the bulbar vascular
centre, went on to establish its limits in the two other dimensions,
by the same method of systematic sections. He discovered that in
each half of the bulb there is a small prismatic space, on destroying
which the reflex vascular constriction is abolished. In this area
a nucleus of grey matter is visible under the microscope, described
by Clarke as the antero-lateral nucleus, in the rabbit.

The main results of Ludwig's pupils were subsequently con-
firmed by Heidenhain, Berkowitsch, Latschenberger, and Deahna.

VII. After Ludwig's School had investigated the bulbar vaso-
constrictor centres, and had shown that after destroying their.

364 PHYSIOLOGY CHAP.

function it was no longer possible to obtain reflex vaso-
constriction on exciting the sciatic, the opinion generally held was
that the cord contained no other centre capable of influencing the '•
tone of the vessels independent of that in the spinal bulb, and
that this was probably the only true vasomotor centre. Very
soon, however, other experimental observations came to light
which showed the fallacy of this view, and led to the opinion that
there were secondary vaso- cons trie tor centres along almost the
whole of the cord, which were able to function after the principal
bulbar centre had been cut out.

Goltz was the first to propose this theory (1864-74). He
found in the frog that the vascular atony was far from complete
after extirpation of the entire brain, including the bulb, and
became so only after destruction of the spinal cord. He further
observed iu dogs that when the cervico-dorsal tract was cut off by
division from the lumbo-sacral, and the animal kept alive until
the vascular atonia of the hind - limbs had disappeared, this
atonia was reproduced on destroying the lumbar cord. He
concluded that the restoration of vascular tone after section of the
cord was due to the presence of vasomotor centres in the lumbar
medulla.

When cut off from the bulb, the spinal vasomotor centres are
also capable of reflexly constricting the vessels, and of raising
arterial pressure, when excited, as was first shown by Schlesinger
(1874) in dogs and rabbits, after he had increased the excitability
of the cord by injecting minute doses of strychnine. This fact
was subsequently confirmed by many observers.

In curarised animals, when the cord is separated from the
spinal bulb, the asphyxia produced by cessation of artificial
respiration suffices to cause vascular constriction, as was first
demonstrated by Kowalewsky and Adamiik (1868). Since this
effect depends on excitation of the spinal centres, it follows that,
after destruction of the cord, asphyxia no longer exercises any
pressor action (Schlesinger, Luchsinger, Konow, and Stenbeck).

The spinal centres for the vaso-constrictors lie not only in the
lurnbo-sacral region (Goltz), but also in the dorsal tract (Vulpian
and Kabierscki). On the other hand, they appear not to exist, or
to be very scanty, in the cervical tract, since aortic pressure is not
affected by section of the cervical cord at any height, after the
bulbar centre has been cut off (Strieker).

The vaso-constrictors in the bundles of the cord for the most
part run directly, and only follow the crossed paths to a minor
extent (Brown-Se'quard and Schiff), as appears from the effects of
hemisection of the cord. They are chiefly mingled with the
sensory and motor fibres to the skeletal muscles which make up
the lateral bundles (Dittmar), as shown by the effects of partial
section in different segments of the cord.

x VASCULAR MUSCLE AND NERVES 365

Nothing certain is known about the anatomical and functional
relations which exist between the spinal vasomotor centres and
the bulbar centre. Certain comparative experiments of Kowalewsky
and Adamiik, Luchsinger, and others on the vascular effects con-
sequent on asphyxia in animals with intact and others with
divided cord lead, however, to the conjecture that the spinal
vaso-constrictor centres are less excitable than the bulbar centre,
For in curarised animals, when the bulb is cut off from the cord,
the rise of arterial pressure at the close of artificial respiration
begins and reaches its maximum, much later than in animals
with intact spinal cord. This leads to the view that the normal
tone of the vascular centre, and its rhythmical or a-rhythmical,
automatic or reflex oscillations, depend principally, if not ex-
clusively, upon the bulbar centre, which, in consequence of its
greater excitability, reacts more quickly to all stimuli, extrinsic or
intrinsic.

Just as there are vaso-constrictor centres below the ruling
bulbar centre, so it seems logical also to assume the existence of
vaso-constrictor centres above the bulb, i.e. in the brain. But the
experiments adduced in this connection give no convincing
evidence in favour of such a hypothesis, since they are susceptible
of various interpretations. Excitation of the cerebral peduncles
in curarised animals is followed by a pressor effect (Budge) ; on
stabbing the anterior or posterior corpora quadrigemina, vaso-
constriction followed by dilatation is obtained (Eckhard) ; if the
corpora striata or the internal capsule are electrically stimulated,
there is rise of arterial pressure (Danilewsky and Strieker) ; when
the cortex, particularly in the region of the so-called motor zone,
is electrically excited, a more or less distinct pressor effect ensues,,
even if no epileptic fit is set up (Danilewsky, Bochefontainer
Richet, Franqois-Franck and others). These phenomena may be-
explained in the sense that there are no true vaso-constrictor
centres in the cerebrum, but only simple nerve paths, which throw
the bulbar vasomotor centres into activity, like the afferent
peripheral nerves. The effects of lesions in these parts, however,
seem to witness more than those of stimulation to the presence
of true vaso-constrictor centres in the brain.

After circumscribed extirpation of certain points upon the
cerebral cortex in the region of the motor zone, a marked and
fairly protracted rise of temperature in the hind-limbs has been
observed (Eulenburg and Landois) ; in clinical paralysis from a
variety of central lesions the same effect may be observed in the
paralysed limbs, as well as ecchymosis in different organs, notably
in the lungs and joints (Charcot and others).

VIII. We have fewer data in regard to the localisation of the
vaso-dilator centres in the several parts of the central nervous
system. It seems highly probable, however, that they are no less

366 PHYSIOLOGY CHAP.

widely distributed than the vaso-constrictor centres, and that
there is in the bulb, along with the controlling centre which
normally regulates the constriction of the vessels, another con-'-
trolling centre which regulates their relaxation, so that the slow
oscillations of vascular tonicity should be regarded as the effects of
the alternating functional predominance of one or other of the
two opposing bulbar vasomotor centres. The few data relating to
this subject may be briefly summarised.

The rapid and infallible effect of central excitation of the
depressor nerves, which is antagonistic to the effect consequent on
central stimulation of the sciatic or other large nerve trunks, in
itself makes the existence of a controlling vaso-dilator centre
highly probable (Ludwig and Cyon). It has so far proved
impossible to demonstrate that it is situated in the medulla.
Certain experiments of Laffont (1880) are, however, of interest in
this connection. He observed as the effect of puncturing the
floor of the fourth ventricle, an active dilatation of the hepatic
vessels, which would therefore seem to depend not on the destruc-
tion, but on the stimulation of the centre. On the following day
stimulation of the depressors in the same animal failed to produce
the customary fall of blood pressure, probably in consequence of
paralysis due to the after-effects of the puncture in the bulbar
vaso-dilator centre.

The following experimental results prove the existence of
vaso-dilator centres in the cord as well. In dogs that have
survived transverse division of the spinal cord at the level of the
last dorsal vertebra, mechanical stimulation of the penis is able to
evoke erection. After destruction of the lumbar cord this effect
is abolished (Goltz). In the same dog, with divided cord, the
central excitation of one sciatic produces active dilatation of the
paw on the opposite side (Goltz, Masius and Vanlair, Ustimowitsch
and others). When the cervical cord is excited, aortic pressure
falls (Johannson) ; there is dilatation of the vessels of the ears,
cheeks, and corresponding mucosa (Dastre and Morat); of the
vessels of the mesentery and intestinal walls (Vulpian); and of
those of the penis (Eckhard). After division of the cord at the
level of the first or second dorsal vertebrae, central excitation of
the brachial plexus causes a fall in aortic pressure (Smirnow).

Again, the existence of cerebral vaso-dilator centres is rendered
probable by the fact that electrical stimulation of the cortex at
certain points, particularly of the parietal lobe, produces not a
rise but a fall of pressure in the aorta (Bochefontaine, Strieker,
Bechterew, and Mislawsky). These are probably the centres
whose activity causes the sudden blush that accompanies psychical
emotions.

In 1893 Bayliss, after describing various experimental results
on vascular reflexes, put forward the hypothesis that " the vaso-

x VASCULAK MUSCLE AND NEEVES 367

motor centre consists of a constrictor and a dilator part, the
depressor nerve acting in an inhibitory manner on the former and
in an exciting manner on the latter, while pressor nerves act in
an opposite way on both." Considerable support is given to this
view by his recent work (1908) on the reciprocal innervation in
vasomotor reflexes. It appears that in depressor reflexes there is,
along with inhibition of tone in the vaso-constrictor centres, an
excitation of vaso-dilator centres. Corresponding effects, although
more difficult to demonstrate, take place in the pressor reflexes.
The action of strychnine upon the vasomotor centres affords a
strict analogy with its action as demonstrated by Sherrington in
the case of the reflexes to voluntary muscle, i.e. conversion of the
inhibitory phase of all vascular reflexes into an excitation. The
depressor nerves cause a rise of blood-pressure under full doses of
the alkaloid by exciting the constrictor centre with the same
mechanism that normally inhibits it.

BIBLIOGRAPHY

In addition to the copious information contained in the general and special
treatises referred to in previous chapters, the student may consult _ the following
monographs and memoirs : —

M. SCHIFF. Untersuchungen zur Physiologic des Nervensystems. Frankfurt a.

M., 1855. Lehrbuch der Physiol., I. Jahr., 3859. Recueil des memoires

physiologiques. Lausanne, 1194.

CL. BERNARD. Le9ons sur la physiologie du systems nerveux. Paris, 1858.
ECKHARD. Beitrage zur Anat. und Physiol. 1863.
LUDWIG und THIRY. Sitz. Ber. d. kais. Akad. d. Wiss., 1864.
LUDWIG und CYON. Ber. d. sachs. Gesellsch. d. Wiss., 1866.
LOVEN. Ber. d. sachs. Gesellsch. d. Wiss., 1866.

v. BEZOLD und BEVER. Untersuchungen aus dem Laborat. in Wiirzburg, 1867.
BROWN-SEQUARD. Lecons sur les nerfs vaso-moteurs. Paris, 1872.
Mosso. Ber. d. sachs. Gesellsch. d. Wiss., 1874.

GOLTZ. Arch. f. path. Anat., 1864. Arch. f. d. ges. Physiol., 1874-75.
VULPIAN. Le9ons sur 1'appareil vaso-moteur, 1875.
HEIDENHAIN und GR.UTZNER. Arch. f. d. ges. Physiol., 1877.
GASKELL. Journal of Anat. and Physiol., 1887.

DASTRE et MORAT. Recherches sur le systeme nerveux vaso-moteur. Paris, 1884.
STBIGKER. Medicin. Jahrbiicher, 1886.
PATRIZI. Arch. ital. de biologic., xxviii. 1897.
CAVANI. Ibidem, vol. xxxix., 1903.
PIOTROWSKI. Arch. f. d. ges. Physiol., 55, 1894.
BAYLISS. Journal of Physiol., Bd. 26, 1901.
ASHER. Die Innervation der Gefasse. Ergebnisse der Physiologie, I, 2. 1902.

(Sixty-eight memoirs are cited in this review.)
BAYLISS. Die Innervation der Gefasse. Ergebnisse der Physiologie, V, 1906.

(Seventy-four memoirs are cited in this article, which is the continuation of

the preceding.)

Recent English Literature : —

W. T. PORTER and H. G. BEYER. The Influence of the Depressor Nerve to the
Vasomotor Centre. Amer. Journ. of Physiol., 1901, iv. 283-299.

W. M. BAYLISS. On the Origin from the Spinal Cord of the Vaso-dilator Fibres
of the Hind-limb and on the Nature of these Fibres. Journ. of Physio!.,
1900-1901, xxvi. 173-209.

368 PHYSIOLOGY CHAP, x

W. HUNTER. On the Presence of Nerve-fibres in the Cerebral Vessels. Journ. of

Physiol., 1900-1901, xxvi. 465-469.
W. M. BAYLISS. On the Local Reactions of the Arterial Wall to Changes of

Internal Pressure. Journ. of Physiol., 1902, xxviii. 220-231.
S. J. and CLAKA MELTZER. A Study of the Vasomotor Nerves of the Rabbit's

Ear contained in the Third Cervical and in the Cervical Sympathetic Nerves.

Amer. Journ. of Physiol., 1903, ix. 57-68.
W. E. DIXON and T. G. BRODIE. Contributions to the Physiology of the Lungs.

Part II. On the Innervation of the Pulmonary Blood-vessels ; and some

Observations on the Action of Suprarenal Extract. Journ. of Physiol., 1904,

xxx. 476-502.
A. J. CARLSON. Vaso-dilator Fibres to the Submaxillary Gland in the Cervical

Sympathetic of the Cat. Amer. Journ. of Physiol., 1907, xix. 408-416.
W. T. PORTER, H. K. MARKS, and J. B. SWIFT. The Relation of Afferent

Impulses to Fatigue of the Vasomotor Centre. Amer. Journ. of Physioi.,

1907-1908, xx. 444-450.

W. T. PORTER and H. K. MARKS. The Effects of Haemorrhage upon the Vaso-
motor Reflexes. Amer. Journ. of Physiol., 1908, xxi. 460-465.
W . M. BAYLISS. On Reciprocal Innervation in Vasomotor Reflexes and the

Action of Strychnine and of Chloroform thereon. Proc. Roy. Soc., 1908, Ixxx.

series B, pp. 339-375.
W. M. BAYLISS. The Excitation of Vaso-dilator Nerve-fibres in Depressor

Reflexes. Journ. of Physiol., 1908, xxxvii. 264-277.
"W. T. PORTER and R. RICHARDSON. A Comparative Study of the Vasomotor

Reflexes. Amer. Journ. of Physiol., 1908-1909, xxiii. 131-140. •
T. SOLLMAN and J. D. PILCHER. The Reactions of the Vasomotor Centre to

Sciatic Stimulation and to Curare. Amer. Journ. of Physiol., 1910, xxvi.

233-259.

CHAPTER XI

CHEMISTRY AND PHYSICS OF RESPIRATORY EXCHANGES

CONTENTS. — Early notions of the importance of respiration (Aristotle, Galen,
Leonardo da Vinci, van Helmont, Boyle, Hook, Fracassati, Lower, Mayow). 2.
Modern doctrines (Black, Bergmann, Priestley, Lavoisier). 3. Theory of gas
exchanges in the lungs and tissues (Lagrange and Spallanzani, W. Edwards).
4. Extraction of gases from the blood (Magnus, L. Meyer, Hoppe-Seyler, Ludwig,
Prliiger). 5. Varying content of arterial, venous, and asphyxiated blood.
6. State of the oxygen in the blood. 7. State of the carbonic acid in the blood.
8. Tension of gases in venous and arterial blood and in inspired >and expired air ;
theory of pulmonary gas exchange by diffusion and by secretory processes. 9.
Theory of gas exchanges in the tissues. 10. The respiratory quotient and its
variations. Bibliography.

JUST as the Circulation provides for the exchange of fluid materials
between the blood and the tissues, so Respiration provides for the
exchange of gaseous materials between the environment and the
blood, and between the blood and the tissues.

We have already seen that the function of respiration is
common to all living beings (see Chap. II. 4 ; Chap. III. 3). Even
Pasteur's anaerobes develop carbonic acid, utilising the oxygen
which is combined with the organic substances, and by its means
producing exothermic reactions, such, i.e., as the liberation of energy
in the form of heat. They thus fulfil the function of respiration,
albeit in a different way from other living beings, so that it cannot
be said that they do not breathe. The vast majority of living
creatures, however, respire free oxygen : the simplest organisms
directly; those which have circulating blood, indirectly, i.e.
through the oxygen of the blood. Among these last we dis-
tinguish external respiration, or the gas exchanges between the
environment and the blood, from internal respiration, or the gas
exchanges between the blood and the tissues. By means of the
first, the venous blood in the lungs and gills is rendered arterial ;
by the second, the arterial blood in the capillaries of the aortic
system or greater circulation is rendered venous.

I. The phenomena of respiration first received a scientific
explanation in modern times, although they arise in physiological
processes that have a first claim on the attention of mankind.

VOL. I 369 2 B

370 PHYSIOLOGY

CHAP.

The need of breathing is, as a fact of common experience, im-
perative; we begin to breathe when we begin to live, we cease
to breathe when we die.

Aristotle (354 B.C.) remarked that all mammals, including the
whales which live in water, breathe air, and that fishes, molluscs,
and crustaceans breathe the water in which they live. Both air and
water serve to refrigerate them, i.e. to temper the innate heat. He
notices that the warmer animals breathe more intensely, and
explains this on the supposition that they had a greater need of
refrigeration — a confusion of effect and cause. Animals in closed
vessels perished, according to Aristotle, because they warm their
environment, and can no longer cool themselves by respiration.

Herophilus and Erasistratus, the leaders of the Alexandrian
School (300 B.C.), had a more physiological notion of respiratory
phenomena. They described a systole and a diastole of the lungs
(expiratory and inspiratory movements), which permitted the
pneuma to penetrate into the arteries, whence it was conducted to
the different parts of the body in order to vivify, that is, to warm
them. It was, however, Galen (see Chap. VI. 2) who first grasped
the chemical function of respiration, since he assumed that the
vital spirit was absorbed in the pulmonary diastole, while the
fuliginous vapours were expelled along with the water vapour in
the pulmonary systole.

With Galen, therefore, as we shall see, begins the experimental
study of the mechanics of respiration. His ideas prevailed
unchanged during the Middle Ages. Servetus' book, Eestitutio
Christianismi, was the last echo — stifled in the flames kindled by
the Catholics of Vienna and the Calvinists of Geneva.

Leonardo da Vinci's conception of the respiratory function
(1452-1519) was far superior to Galen's in accuracy and lucidity.
Leonardo was one of the most universal geniuses the human race
has ever seen, inasmuch as he combined with the eminent gifts of
an artist the experimental instinct and divining power of the man
of science, in the most modern sense of the word. In the scientific
aphorisms published after his death there is a brilliant study on
the nature of a candle flame, which is a complex physical and
chemical problem. In this study, among other admirable observa-
tions, he affirms that " the flame first disposes of the material that
is to nourish it (i.e. reduces to the gaseous state the combustible
matter of the candle), and then feeds itself on the same . . .
where the air is not fitted to maintain the flame (i.e. where the
air has been consumed by the flame), no flame can live, neither
any terrestrial nor aerial animal . . . where flame cannot live, no
animal that breathes can sustain existence" (Codice Atlantico,
folio 170, fasc. XXIII. p. 963).

These words, besides being an inspired conception of the analogy
between the phenomena of combustion and of respiration, convey

xi KESPIKATOKY EXCHANGES 371

an experimental fact of the highest importance, although Leonardo
adduces no evidence.

The first real discovery in the field of experimental chemistry
was made by Jean Baptiste van Helmont (born at Brussels, 1577 ; d.
1644), noblest of the experimental alchemists, precursor of Priestley
and Lavoisier, the founders of modern chemistry. He found that
on burning coal and in the fermentation of wine, a gas which he
called gas silvestre escaped, which is incapable of maintaining a
flame, and produces asphyxia and death in animals. This gas
may develop in the heart of the earth, as in the famous Grotta del
Cane near Naples ; it bubbles up in certain mineral waters, as at
Spa, and can also be evolved from the calcareous concrements
formed in the crab's stomach (the so-called " crab's eyes") by dis-
solving them in vinegar. In short, van Helmont's gas silvestre is
nothing else than the carbonic acid of modern chemists. Haller
used this discovery of the Belgian alchemist to refute the Aristo-
telian theory of respiration which Cesalpinus and Harvey had
sought to resuscitate.

In the year 1670 another distinguished philosopher and
investigator, Eobert Boyle (1626-1691), the leader of the group of
scientific men who formed the nucleus of the Koyal Society, proved,
with the help of the pneumatic machine introduced by the
Magdeburg physicist, von Guericke, that not only do all land
animals perish in a vacuum, but all water animals as well, showing
that these equally require the air which is dissolved in the water
they inhabit. He concluded from many experiments that the air
contains a vital substance — thus adumbrating the oxygen of
modern chemistry, which enters into the phenomena of combustion,
respiration, and fermentation. He also confirmed, experimentally,
the fact already advanced by Leonardo da Vinci and van Helmont,
to the effect that the air becomes unbreathable through respiration
— not because it gets heated, but because it suffers chemical
change.

Eobert Hook, friend and contemporary of Boyle, pointed out
the need of incessant renewal of the air in the lungs for the
maintenance of life. Vesalius had noticed, a hundred years
previously, that in order to prolong the life of a dog after opening
of the thorax and consequent retractation of the lungs, it was only
necessary to inflate them rhythmically with air ; but he brought
forward no conclusions of importance in regard to the physiology
of respiration. Hook perfected the method of artificial respiration
in the dog with opened thorax by rhythmically blowing air from
a bellows into the lungs, or by .continuous insufflation after
making an opening on the surface of each lung. In both cases he
saw that the animal could be kept alive for a prolonged period,
and only died when the air stagnated in the lungs from cessation
of the rhythmical or continuous ventilation. He concluded that

372 PHYSIOLOGY CHAP.

the significance of respiration lay in the renewal of the pulmonary
air and not in the alternate expansion and contraction of the
lungs, as was believed by certain iatro-mechanicians.

The ancients were undoubtedly aware of the difference in
colour between arterial and venous blood. It was perhaps owing
to this difference that they termed the pulmonary artery vein, and
the pulmonary veins arteries. It was also known to the older
surgeons that the clot formed from the blood extracted by bleeding
exhibits the scarlet colour of arterial blood in the upper layers, and
the darker colour of venous blood in the deeper layers. In 1665
it was discovered by Fracassati, a famous physician of Bologna,
that the florid colour of the superficial layer of the clot was pro-
duced by the action of the air, and that it sufficed to invert the
clot for the darker layers, which had been in contact with the
walls of the vessel containing it, to assume the same hue as the
arterial blood.

This was confirmed by Lower (1669), another friend and
collaborator of Boyle, who at the same time discovered a further
weighty fact : he observed, namely, that when artificial respiration
was used with the opened thorax, the venous blood became arterial,
not in the heart, but in the lungs, while the reduced blood of the
lungs also became venous if artificial respiration was interrupted.

So far nothing positive was known about the chemical processes
that take place in respiration, and the analogy between respiration
and combustion was merely guessed at, not proven.

The pioneer in the chemistry of the air and the doctrines of
respiration, combustion, and oxidation of metals was John Mayow
(1640-1679). In a series of original experiments published at Oxford
when he was twenty-eight, he expressed his conviction that the
air was not a simple body but a mixture of at least two different
gases or " spirits/' one of which (termed by him spiritus nitro-
aereus or igneo-aereus) is competent to support life by passing into
the blood during respiration, and rendering it florid and able to
ferment and develop heat. It is this same vital gas which
combines with burning bodies, generates acids, and rusts iron.
The air that remains after the consumption of the spiritus nitro-
aereus is inadequate for life, for combustion, for the rusting of
metals. The experiments by which Mayow was led to these
remarkable results, which virtually involved the discovery of
oxygen and nitrogen, consisted chiefly in the introduction of small
animals and lighted candles into a closed vessel over water. He
noted the diminution of the volume of air in consequence of
respiration and combustion, and the cessation of life and of
combustion after a certain time, due not to the accumulation of
fumes, but to the consumption of the igneo-aereal particles.
Unfortunately this genius, who antedated the greatest discovery
of the chemistry of the air by a century, died at the age of thirty-

xi RESPIKATOKY EXCHANGES 373

three, a few years after the publication of his early experiments.
The great importance of his unfinished work was overlooked, and
it hardly had any influence upon the progress of physiology.

II. Before Mayow's notions of the composition of the air could
be regarded as a definite achievement, it was necessary to perfect
the methods of investigating the chemical study of gases, more
especially the art of manipulating them .like solid or fluid bodies.
Many workers contributed to the building up of this technique,
in particular Hales (1678-1*761), who was the promoter of the so-
called pneumatic chemistry, by inventing the method of collecting
gases in an inverted test-tube, suspended in a vessel of water or
mercury into which the gas was passed by means of bent tubes.
By this method, known as the eudiometric, Joseph Black, Professor
at Glasgow in 1757, again isolated and studied the properties of
that gas which van Helmont termed gas silvestre, to which Black
gave the name of " fixed air." He snowed experimentally that it
was a product of the respiration of man and other animals. On
blowing through lime water or a solution of caustic alkali, he saw
that the lime was precipitated and the alkali was rendered mild.
Bergmann of Stockholm subsequently (1772) continued Black's
investigations on " fixed air," which he termed " ae'real acid,"
finding it, though in small quantities, in the atmosphere. Black
and Bergmann, in these weighty experiments, were the immediate
precursors of Priestley and Lavoisier, who are usually accredited
with the prestige of being the founders of modern chemistry.

Priestley (1733-1804) eagerly pursued the researches of his
predecessors ; in 1772 he experimented with the object of seeing
whether it were possible to restore the vital properties of air that
had deteriorated in consequence of animal respiration and com-
bustion, and after many fruitless experiments he discovered that
plants thrive in this air and renew it for purposes of animal life
and combustion. In 1775 he discovered that red precipitate of
mercury on calcination developed a gas which was exceedingly
favourable for combustion and animal respiration ; this (in accord-
ance with Stahl's doctrine which then predominated) he termed
dephlogisticated air, i.e. air free from the imaginary principle
known as phlogiston. This was the same gas that Mayow called
nitro- ae'real or igneo- ae'real, and which Priestley succeeded in
obtaining pure, and isolated from the other atmospheric gases.
By various other processes he also isolated the irrespirable gas
obtained from air, after burning coal or sulphur, and dissolving
the products of combustion in water. He studied the properties
of this and called it phlogistic air, i.-e. air charged with phlogiston.
Lastly, in continuation of the experiments above described, of
Fracassati and Lower (the results of which had been confirmed
by Cigna and Hewson in 1773), Priestley showed that the de-
phlogisticated air which he had discovered was essential for the

374 PHYSIOLOGY CHAP.

conversion of venous into arterial blood, and that the blood, even
through an animal membrane, makes normal air irrespirable and
unable to support combustion, by converting it into phlogistic air.

After Priestley's discoveries it remained for Lavoisier (born in
Paris, 1743 ; infamously guillotined March 8, 1794) to earn the
glory of rearing a solid and complete edifice on their basis, both as
regards the chemical composition of the air, and the phenomena
of combustion and respiration.

In order to refute the cumbrous doctrine of Stahl's phlogiston,
it was only necessary for Lavoisier to employ the balance, and to
show that the so-called earths or metallic oxides are heavier than
metals. Stahl's theory presupposed that rnetals, when converted
into oxides, lost their phlogiston, and therefore lost in weight, the
oxides on conversion into metals becoming phlogistic and therefore
gaining in weight. Lavoisier (1776) established that the air is
not a simple fluid which robs the igneous principle from animals
and gives it up to plants, but a mixture of two fluids, one
inadequate to support life, which he termed azote, the other
eminently respirable, which he called oxygen. The former corre-
sponds with Priestley's phlogistic, the latter with his dephlogis-
ticated air.

In 1780 Lavoisier discovered the chemical composition of van
Helmont's gas silvestre (the " fixed air " of Black) and showed it
to be the result of the combination of carbon with oxygen in
definite proportions. He succeeded in correlating the formation
of carbonic acid gas in expired air with the synchronous con-
sumption of oxygen, and conceived of pulmonary respiration as a
phenomenon of combustion, in which, under the influence of life,
the oxygen combines with the carbon exhaled from the body, and
becomes the principal source of the internal heat generated by the
animal. Nor was this all ; by means of the balance he showed
that the amount of oxygen consumed in the respiratory work of
animals is greater than that contained in the carbonic acid given
off. The recent discovery of the chemical composition of water,
made by Cavendish (1781), and soon after confirmed by Lavoisier,
'enabled him to account for this fact and to complete his theory of
the chemistry of respiration, which he conceived as a double
combustion, from which are formed carbonic acid and water. He
made this deduction from repeated experiments, which enabled
him to conclude that "respiration is a slow combustion of carbon
and hydrogen, perfectly similar to that which occurs in a burning
lamp ; and from this point of view animals which breathe are true
combustible bodies that burn and are consumed."

In 1789 Lavoisier published with Seguin a large number of
researches that are of fundamental importance to the theory of
respiration. The two experimenters noted that the intensity of
respiratory combustion does not vary essentially, whether the

xi EESPIEATOKY EXCHANGES 375

animal breathes pure oxygen or a mixture of fifteen parts nitrogen
and one of oxygen ; that during respiration the nitrogen does not
sensibly increase nor diminish, and may without injury be
substituted for hydrogen, which also behaves as an indifferent gas ;
that during digestion and the muscular movements the intensity
of respiratory combustion increases ; that lastly, the consumption
of oxygen in man increases sensibly when the external temperature
is lowered.

As regards the seat of respiratory combustion, Lavoisier was
less happy than in his previous researches, for he asserted with
Seguin that it took place in the lungs, where the oxygen of the
air encountered the combustible material, represented by a hydro-
carbonous fluid. This hypothesis, which makes the lungs the seat
of respiratory combustion, was open to grave objections. It was
observed that the temperature of the lungs is no higher than that
of the other internal organs, making it dubious whether heat could
spread thence to the rest of the body. Starting from this fact,
Lagrange (born at Turin, 1736 ; died 1813), one of the most
illustrious of mathematicians, was the first to rectify Lavoisier's
error. He maintained the hypothesis that only gas exchanges
take place in the lungs, in which the blood circulating through
them yields its carbonic acid to the air and absorbs oxygen from
it ; and that respiratory combustion is accomplished in every part
of the body to which the blood circulates.

III. The earliest experimental proofs of the theory of internal
or tissue respiration, as foreshadowed by Lagrange, were given by
Lazzaro Spallanzani (1729-1799), who claims an important place
in the history of the chemistry of respiration. In a long series of
comparative studies on the respiration of a great number of
animals, terrestrial, aquatic, vertebrate, aud invertebrate, he
extended the doctrine of Lavoisier, proving that oxygen is in every
case essential to life, and that in all it is absorbed by the organs of
respiration (lungs, gills, trachea, skin) and carried to the circula-
tion, where it determines the vitality of the tissues by entering
into combination with them.

Further, by ingenious experiments on snails he showed that
excretion of carbonic acid is independent of absorption of oxygen,
since it remains almost always constant, even when these creatures
are enclosed in tubes, plunged in a mercury bath, and filled either
with water that has been boiled and deprived of gases by the air-
pump, or with nitrogen or hydrogen.

The Memorie su la respirazione is the posthumous work of the
Abbe* Spallanzani, and contains only a few of his observations.
After his death the protocols of his experiments were confided to
his friend the Genevese scientist and librarian, Jean Senebier, who
extracted from them the materials for a work entitled Rapport de
I'air avec les dtres organises (Geneva, 1807). This is a valuable

376 PHYSIOLOGY CHAP.

collection of experimental facts, showing how much of the progress
of our science is due to this illustrious physiologist. Undeniably,
however, it lacks that concise method and critical elaboration
which it would have received had the author been able to complete
his own work.

The subsequent researches of William Edwards (born in
Jamaica, 1*776; died Versailles, 1842) were on the lines of
Spallanzani's most important experiments. On bringing frogs,
whose luugs had been emptied by compression of the flanks, under
a bell-jar of hydrogen immersed in mercury, Edwards observed
that the animal in the space of a few hours developed an amount
of carbonic acid almost equal to the volume of its body. Similar
results were obtained from experiments on fish, which breathe
through their gills. In order to prove that the same fact holds
for mammals, which die as soon as they are deprived of oxygen, he
took newborn animals, which have a longer resistance to asphyxia,
and showed that when immersed in an atmosphere of hydrogen,
they continue to exhale carbonic acid. These facts are only the
confirmation and generalisation of those enunciated twenty-five
years earlier by Spallanzani ; but Edwards deduced from them
more clearly and explicitly the erroneous nature of Lavoisier's
theory of pulmonary combustion, and the proof of Lagrange's
theory of pulmonary gas exchanges. Carbonic acid (as he
approximately concluded) is exhaled from the body independent of
the entrance of oxygen into the lungs and its absorption by the
blood. It is probably derived from the tissues, and may be
already formed and dissolved in the venous blood, from which it is
exhaled on circulating through the pulmonary vessels.

Collard de Martigny (1830), Johannes Miiller (1835), Bischoff
(1837), Marchand (1844), with improved and varied methods of
experiment, obtained the same results as Spallanzani and
Edwards.

IV. The theory of external respiration as a gaseous exchange
between the air contained in the pulmonary alveoli and the blood
gases circulating in the pulmonary capillaries, and the theory of
internal respiration in the sense of a gaseous exchange between
the blood gases circulating in the aortic capillaries and those
produced by the living elements of all the tissues, received a solid
experimental basis from the researches on the quality and quantity
of the gases contained in the blood, and the inter-comparison of
the gases extracted from arterial and those extracted from venous
or.asphyxial blood.

When in 1824 Edwards published his essay, The Influence of
Physical Agents on Life, in which the theory of the respiratory
gas exchanges was clearly formulated, some scanty data existed in
support of the hypothesis that the blood was the vehicle of these
exchanges, and held in solution or loose combination both the

xi EESPIKATORY EXCHANGES 377

oxygen and the carbonic acid. The blood gases were first extracted
with the vacuum pump by Boyle and Mayow ; Humphry Davy
(1803) was the first to extract them by the method of warming,
and to recognise that arterial blood contains little carbonic acid
and much oxygen.

Priestley (1776), Fontana (1804), Nasse (1816), Brande (1818),
Vauquelin (1820) and others were able either by the method of
simple diffusion, by bringing the blood into contact with indifferent
gases such as hydrogen and nitrogen, or by agitating the blood with
the said gases or passing them through it, to determine the fact that
it holds both oxygen and carbonic acid in solution. These results,
obtained with somewhat loose methods, were, however, contested
by other distinguished physiologists, so that John Davy, Johannes
Miiller, Gmelin, Tiedemann and others agreed in denying the
presence of free gases in the blood, while Vogel, Nasse, Scudamore,
Th. Bischof, Collard de Martigny, and van Enschut maintained
that carbonic acid was not found in the blood in a state of
solution.

It was Magnus (1837), Professor of Physics at Berlin, who put
an end to this uncertainty, and performed his experiments on the
gases of the blood with the scientific method that was indispensal >le
to make his results convincing. He extracted the gases of the
blood by means of the Torricellian vacuum, with an ingenious
apparatus which as it were combined the mercury pump and the
pneumatic machine. As the result of his analysis, he stated that
both arterial and venous blood contain not only carbonic acid, but
oxygen and nitrogen as well, and that carbonic acid preponderates
in venous, oxygen in arterial blood. He was the first who attempted
to account for the mechanism of the pulmonary gas exchanges,
considered as an effect of simple diffusion, according to the physical
law formulated by J. Dalton in 1805.

In 1857, however, Lothar Meyer demonstrated that the amount
of oxygen liberated from the blood does not increase proportionally
with the lowering of pressure, as it should according to Dalton's
law, and that it is only when the pressure acting on the blood is .
reduced to -fa that the oxygen of the blood begins to dissociate.
On combining the vacuum method of extracting the blood gases
with the method of heating to 40° C. blood that had been
extracted and diluted with a quantity of water previously boiled
and deprived of its gases, he completed and partially rectified the
conclusions of Magnus.

While approximately true, Meyer's data were not yet entirely
accurate, as was shown by the succeeding work of Hoppe-Seyler
(1854), Ludwig (1858), and Pfliiger (1865). They introduced in-
teresting improvements in technique, with the object of obtaining
the maximal quantity of gases that can be extracted from a given
quantity of arterial, venous, or asphyxial blood. In order, as

378 PHYSIOLOGY CHAP.

briefly as possible, to condense the more important conclusions
arrived at in the actual state of science, we must pass from the
historical exposition of the subject to a summary of the experimental
data.

Laws of Absorption and Diffusion of Blood. — In order to 'understand
what follows in regard to the mechanism of respiratory gas exchanges, it is
necessary to recapitulate certain physical laws which are closely bound up
with this process.

Since gases have no definite shape like solids, nor definite volume like
liquids, and since the molecules which constitute them have the property of
mutual repulsion, so, when two gases that do not enter into chemical com-
bination, are brought into contact, they promptly expand one into the other,
until they form a uniform mixture independent of their different densities.
This phenomenon is called the diffusion of gaseV

The force with which the molecules of the gases tend to expand in a space,
and by means of which they exert uniform pressure in every direction, is
called, the tension of gases. Obviously, the greater the number of gaseous
molecules brought together in a confined space, the greater will be the pressure.
It follows that the tension of a gas is inversely proportional to its volume
(Mariotte's law).

Again, when two gases are separated by a porous septum, there is reciprocal
diffusion, but the velocity with which the molecules of each diffuse across the
septum varies according to their densities ; the lighter gases, such as H and
CH4, diffuse more rapidly than Cl and CO, which are heavier. It may be
said approximately, with Graham, that the rate at which gases traverse the
pores of the septum is inversely proportional to the square root of their
densities.

There is a marked attraction between gases and particles of solid porous
bodies, whereby the former are attracted and condensed between the pores of
the latter. Thus, for example, 1 vol. of boxwood charcoal may condense at
12° C., and at ordinary barometric pressure, 35 vols. of C02, 9'4 vols. of O2, 7'4
vols. N, 1-75 vols. H2. This process is termed the absorption of gases by solid
bodies, and is • invariably accompanied by evolution of heat in ratio with the
energy with which the absorption proceeds. Non-porous bodies, too, are
capable of condensing, if not of absorbing on their surface, a layer of the gases
with which they may be brought into contact.

More important for us is the absorption of gases by liquids. In this con-
nection it has been found that the volume of a gas absorbed by a liquid is
independent of its pressure. Since, however, the density of a gas is pro-
portional to the pressure under which it is placed, and since its weight is
equal to the product of volume x density (Boyle, 1662 ; Mariotte, 1679), it
follows that the weight of gas absorbed by a liquid is proportional to the
pressure, although its volume remains the same (Dalton-Henry law). Hence
the gas must be regarded as physically absorbed by the liquid, whence it can
be recovered in quantities proportional by weight to the lowering of pressure
to which it is subjected. When, therefore, the pressure is reduced to zero by
the Torricellian vacuum, the liquid can be deprived of all the gases which it
has absorbed.;

The absorption coefficient of a liquid for a gas is the figure which indicates
that volume of gas which at 0° C. and 760 mm. Hg pressure, is absorbed by
the unit volume of the liquid (Bunsen).

Temperature has great influence on coefficients of absorption. A liquid
absorbs less gas, in proportion as its temperature is higher, and at boiling-
point there is no longer any absorption. It is therefore sufficient, in order to
extract the gases absorbed by any liquid, to heat it to boiling-point.

The degree in which different liquids absorb the same gas, and in which

XI

EESPIEATOKY EXCHANGES

379

the different gases are absorbed by the same liquid, varies considerably.
volume of distilled water is capable of absorbing : —

One

c.

N.

02.

C02.

Air.

0

0-020

0-041

1797

0-025

5

0-018 0-036

1-500

0-022

15

0-015 0-030

1-002

O'OIS

37

0-012 0-025

0-530

0-015

Indifferent salts which are .incapable of combining chemically with gases,
lower the absorption coefficients in watery solutions in proportion to their
concentrations.

In the body it is always with gaseous mixtures in the fluids of the tissues,
and never with isolated gases, that we have to deal. We must, thereforer
investigate the absorption of gas mixtures by liquids. Since gases exert no
reciprocal pressure, one volume of liquid may absorb several gases successively
or simultaneously, in different volumes, according to the respective co-
efficients of absorption, and each gas absorbed is at a tension proportional
with the volume that it occupies in the mixture of absorbed gases. Bunsen
gave to this the name of partial pressure, because it represents the pressure
(in mm. Hg) which each gas would exert in the surrounding atmosphere, if
there were neither absorption nor emission of gas on the part of the liquid.
Since, e.g., the average pressure of atmospheric air is 760 mm. Hg, and it
consists in round numbers of 21 vols. per cent O2 and 79 vols. per cent
N, the partial pressure of the oxygen absorption will be equal to
0-21 x 760=160 mm. Hg, and the partial pressure at which the absorption of
N occurs is equal to 0-79 x 760 = 600 mm. Hg.

During absorption each gas of the mixture diffuses in the liquid in an
amount proportional to the difference in concentration of the adjacent layers,
as Graham shows for other substances in solution. Diffusion ceases and
absorption is complete when in all layers of the liquid, and in the atmosphere
with which it is in relation, complete equilibrium of tension for each of the
gases contained in the atmosphere, or dissolved in the liquid, is established.

The rate of diffusion of a gas through a layer of liquid stands in direct
ratio witli the solubility coefficient of the gas, and in inverse ratio with the
square root of its density. So that, e.g., although the diffusion rate of the
molecules of H2 is greater than that of the molecules of C02, the latter being
more soluble in water than the former, more C02 than H2 passes through a
layer of liquid in a given time.

Generally speaking, the velocity of diffusion of a gas in a liquid is very
low (Duncan and Hoppe-Seyler, 1894). They found that at ordinary
barometric pressure and mean temperature, atmospheric air penetrates
extremely slowly into a given quantity of water closed on all sides,
save at the top where the air enters. After fourteen days of contact,
absorption in the lower layers of the column of water was still incomplete.

V. The most important conclusions from the work carried out
under the directions of Ludwig and Pfliiger confirm the fact
already determined by Magnus, to the effect that the amount of
gas that can be extracted from arterial blood differs considerably
from that of venous blood.

From the average of twelve analyses performed by Pfliiger with
the rapid method, it appears that the arterial blood of the dog

380 PHYSIOLOGY CHAP.

contains 22'6 vols. per cent of oxygen (at 0° C. and 760 mm. Hg),
34'3 per cent of carbonic acid, and 1/8 per cent of nitrogen.

According to an analysis of Setschenow, human arterial blood
contains 21-6 vols. per cent oxygen, 40*3 per cent carbonic acid,
1/5 per cent nitrogen. Some analyses of the blood of herbivores
(sheep, rabbit) made by Sczelkow and Walter give 10'7-13'2
vols. per cent oxygen, 34-45 per cent carbonic acid, 1/8-2-1 per
cent nitrogen.

The gas content of venous blood is more variable, according to
analysis, since it depends on the circulatory velocity and activity
of metabolism in the several tissues traversed. At present we
have only analyses of the blood of the right heart, in which the
reduced venous blood from the whole aortic capillary system meets
and mingles. On the 'average of numerous analyses given in the
tables of Zuntz, the venous blood of the dog contains 7*15 vols.
per cent oxygen less than the arterial blood, 8 '2 vols. per cent
more carbonic acid, and much the same quantity of nitrogen, as
arterial blood.

After asphyxia pushed so far as to kill the animal, the oxygen
does not disappear from the whole of the blood, while the carbonic
acid increases considerably. From a number of analyses of
asphyxial blood made by Setschenow, Holmgren and others, it
appears to contain 0'96 vols. per cent oxygen and 49 '53 per
cent carbonic acid : i.e. there is a deficit of 17'3 vols. per cent
oxygen and 1043 per cent excess carbonic acid, as compared with
normal arterial blood, according to the values obtained by the said
authors.

Method of Extracting Gases from the Blood. — The various forms of
apparatus adopted, after Magnus, for the mechanical extraction of gases from
the blood, are those of Hoppe-Seyler, Ludwig, Lothar Meyer, A. Schmidt,
Pfliiger, etc. They are all based essentially upon the Torricellian vacuum,
and aim at liberating the gases dissolved in the fluids or held in loose
combination. The most perfect form for the rapid and complete extraction
of gases is that of Pfliiger, as represented in Fig. 167.

It consists of three principal parts : the bulb A which receives the
'blood direct from the artery or vein ; the tube for absorption of the water
vapour to dry the extracted gases B ; the mercury pump CD for aspiration
and the reverse, i.e. production of the Torricellian vacuum, and expulsion of
the gases extracted into the eudiometer tube for analysis.

The details of construction of the apparatus are so plain on the diagram
that a minute description is superfluous.

The bulb G is first connected with the tube H by turning the 3-way tap
G. The vessel D is then raised by the handle £, so that the whole of bulb
(7, with which D communicates by means of the strong rubber band Fand
the glass tube E, is filled with mercury. When G is full, communication
with H is closed by a quarter turn of the tap G, and opened to the tube
connected with the desiccating apparatus £, and also with the double bulb A,
after opening the tap P. The vacuum is then started in the apparatus by
lowering the vessel D by means of the handle £, on which all the mercury
passes from G into D, and air rushes in from A and B to G. The tap

XI

BESPIKATOKY EXCHANGES

381

G is then brought back to its first position by a quarter turn, so that C is now
connected with H and no longer with A and 5, while the vessel I) is once
more raised, driving the air out of (7, which fills with mercury. Frequent
repetition of this process (of turning the tap G, alternately with raising and
lowering of the vessel D of the mercury pump) produces a perfect vacuum
throughout the apparatus, which occurs at the exact moment at which the

FIG. 167. — Pfliiger's apparatus for extraction of blood gases. (Explanation in text.)

mercury of the manometer 0, attached to the tube that connects C with #,
falls to zero. The steadiness or oscillations of the manometer column show
whether the apparatus is air-tight or not. .

After making a perfect vacuum, the pointed upper end of the bulb A is
connected with the cannula previously introduced into the blood-vessel
(carotid or jugular). The 2-way tap M is turned so as to fill the connecting
tube with blood which drives the air out, after which another quarter turn
of the same tap lets the blood flow in the required quantity into the bulb A.

382 PHYSIOLOGY CHAP.

Directly the blood rushes into the vacuum it froths up, owing to I the
liberation of the gases. The froth collects in the upper part of the bulb, and
cannot pass through the minute aperture of the cock P. In order to
promote and complete the extraction of the gases, a cylinder of water heated f
to about 60° C. may be applied to the exterior of A. The gases liberated
from the blood pass into the absorption tube B (which contains con-
centrated sulphuric acid in its lower end, and bits of dried pumice-stone
saturated with the same acid along its length) and lose their water vapour,
so that only dried gases reach the vessel G and are ready for chemical
analysis.

The amount of blood run into the apparatus is next determined. Since
the total capacity of the receiver is known, the amount of water still
required to fill it at the end of the experiment is subtracted — the difference
representing the volume of the blood employed. The determination is more
exact if the amount of water absorbed in the tube B is calculated by weighing
B before and after the experiment.

For quantitative determination of the gases extracted from the given
amount of blood, they must be allowed to pass from the holder C into the
eudiometer tube K, which is filled with mercury and inverted over the
mercury trough /. This is easily done by making connection between C
and K by the tap G through H, closing the connection between C and B, and
raising the vessel D by the handle L, so that G acts as a pressure -pump.
Frequent repetition of this process drives all the extracted gases into the
eudiometer.

To determine the volume of the C02, a pellet of caustic potash, moistened
at the surface arid fused at the end to a platinum wire, is introduced into the
eudiometer. When all the carbonic acid is converted into potassium
carbonate, the pellet is removed by cautiously withdrawing the platinum
wire. The diminution in volume of the gas in the eudiometer gives the
volume of C02 extracted from the blood.

The volumetric determination of the 02 is effected in a similar way
by introducing a pellet of phosphorus on a platinum wire, or a ball of filter-
paper saturated with a solution of pyrogaUic acid in caustic potash, which
greedily absorbs oxygen. After the ball has been removed, the further
diminution of gas in the eudiometer shows the volume of 02 extracted from
the blood.

The volume of gas remaining in the eudiometer after the absorption of
C02 and O2 consists of nitrogen.

VI. Some notion of the quantity of the gases that can be
extracted from the blood is a necessary premiss to determining
the state in which they are found, whether free, or in simpb
physical solution, or in chemical combination.

As regards oxygen, it may be argued from the large amount
contained in the blood that it cannot be merely in a state of\
solution. As a matter of fact the coefficient of absorption of'
water for oxygen stands at a rather low figure ; at 0° C. and \
760 mm. Hg, of an atmosphere of pure oxygen, not more than
4 vols. per cent are absorbed, hence from the air (in which the
partial pressure of oxygen is five times less) under 1 vol. per
cent is absorbed. On raising the temperature of the water to that
of the body, the coefficient of absorption for oxygen is still further
lowered. It is also lowered considerably if the water is replaced
by a watery solution isotonic with blood plasma. Obviously, /

xi RESPIKATOEY EXCHANGES 383

therefore, the 22 - vols. of oxygen contained in arterial blood
must, to a large extent, be in a state of chemical combination
(Liebig, 1851 ; L. Meyer and Fernet, 1857). We know, in fact, that
the oxygen absorbed by the blood is in loose combination with the
haemoglobin of the erythrocytes, which gives rise to the formation
of oxy haemoglobin (Hoppe-Seyler, 1864 ; see Chap. IV. 7).

The proof of this fact, one of capital importance in the
physiology of the respiratory exchanges, is that a watery solution
of. 14 per cent pure haemoglobin (which corresponds to the normal
haemoglobin content of the blood) is capable of absorbing and
chemically fixing as much oxygen as an equal volume of blood, and

FIG. 168. — Curve to show percentage variations of oxy haemoglobin in a solution of 14 per cent blood -

Sigment, with variations of partial pressure of the atmospheric oxygen with which it comes
i contact. (Hiifner.) Quantity of oxyhaemoglobin in Tfn along axis of ordinates ; partial
pressure of oxygen in mm. Hg, along axis of abscissa.

by means of the Torricellian vacuum it is possible to extract as
much oxygen from the same solution as from blood.

It was fundamental to the conception of oxygen absorption in
the blood, to determine to what point the quantity that combines
with haemoglobin depends on its partial pressure in the atmosphere.
Bohr (1885) and Hiifner (1888) made a number of experiments
with this object. The method consisted in placing a given quantity
of defibrinated blood, or better, of 14 per cent solution of pure haemo-
globin (which, as we have said, corresponds with the haemoglobin
content of the blood) in contact either with normal air, or with
artificial air containing a considerably less amount of oxygen per
cent; and then shaking it. It is then determined how much
oxygen combines with, or is dissociated from, the haemoglobin
on a rise or fall of its partial pressure in the mixture of gases
Hufner's results are clearly expressed in the diagram (Fig. 168),

384 PHYSIOLOGY CHAP.

which represents the curve of dissociation of oxygen and haemo-
globin, in proportion with the fall of partial pressure in the mixture
of gases. The curve shows that at the partial pressure of 150 mm.
Hg (which is a little lower than that of the oxygen of normal air) '
almost the whole of the haemoglobin (about 98 per cent) combines
with the oxygen ; that the dissociation proceeds very slowly till a
partial pressure of 50 mm. (which corresponds to about a third of
the partial pressure of the oxygen of normal air) is reached ; and
that it only becomes rapid at a partial pressure of 25 - 10 - 5 mm. Hg,
These results show that the blood, in consequence of the chemical
affinity of haemoglobin for oxygen, is able to provide itself with an
abundant supply, even when the organism is breathing an atmo-
sphere very poor in this gas ; while, on the other hand, the absorption
of oxygen in the blood cannot rise far above the normal, even when
the organism is made to respire an atmosphere of pure oxygen.

A proof of this great independence of the absorption of the
oxygen of the blood from its partial pressure in the atmosphere is
shown in the fact that mammals do not exhibit any visible dis-
turbance of respiratory function when they are made to 'breathe an
artificial atmosphere three times richer, or one-half poorer in oxygen
than the normal air ; and it is only when the partial pressure of
oxygen falls below this limit that the respiratory movements are
progressively accelerated, and death from lack of oxygen only
occurs when the partial pressure of 00 is lowered to 3*5 mm. Hg
(W. Mliller, P. Bert).

On examining in dogs how the oxygen content of arterial blood
varies with the progressive rarefaction of the atmospheric air
respired, it was found that it remains normal up to a total
pressure of 410 mm. Hg; that it diminishes slightly at a
pressure 378-365 mm. ( = about half an atmosphere) ; and that it is
only at a total pressure of 300 mm. that any conspicuous diminu-
tion of oxygen can be observed in arterial blood (Frankel and
Geppert). These facts agree with the observations made during
aerostatic ascents, which show that respiratory disturbances only
begin at a height of 5000 meters ( = 400 mm. Hg). On the
other hand, it has been observed on the high plains of the Andes
that men and animals can live as well at 4000 metres altitude as at
the level of the sea.

Not quite the whole of the oxygen is in chemical combination
with haemoglobin ; a small fraction of it (0'1-0*2 vols. per cent)
is normally held in solution in the plasma. This quantity is,
however, less, under normal conditions, than what can be absorbed
by an equal volume of distilled water at the same tempera-
ture. It may vary according to the Henry-Dalton law, i.e. the
volume of oxygen dissolved in the plasma is proportional to its
tension. In proportion as the tissue elements absorb the oxygen
of the plasma, and the tension lessens, there must necessarily

xi EESPIKATOKY EXCHANGES 385

be dissociation of the haemoglobin of the erythrocytes from the
oxygen, which diffuses in the plasma to re-establish equilibrium
between the tension of the oxygen in the plasma and the corpuscles.

VII. The carbonic acid of the blood is also for the most part
in chemical combination, and to a minimal extent in solution.
This is proved by the fact that the coefficient of absorption of this
gas in water, at 37° C., is about 0 57, while on the other hand we
have seen that arterial blood only contains 34 and venous blood 42
vols. per cent. Unlike oxygen, however, which enters into com-
bination only with haemoglobin, carbonic acid unites chemically
with many substances, both of the plasma and of the corpuscles.

Among the substances capable of holding the carbonic acid of
the blood in readily dissociable forms, great stress was formerly
laid upon sodium carbonate, which as a base (see p. 132) abounds in
the ash of plasma. The phenomena of electrolytic dissociation of
the solutions of this salt have, however, demonstrated that it can
only be of very secondary importance in the chemical combination
of the carbonic acid of the plasma, by converting it into bi-carbonate.
In fact, according to the researches of Bohr, a very dilute solution
of 015 per cent sodium carbonate becomes almost saturated at a
pressure of only 10 mm. Hg of carbonic acid, while on raising the
pressure to 120 mm. there is no appreciable increase in the amount
fixed or dissolved. Hence it is evident that sodium carbonate is
incapable of fixing more than a minimal amount of the carbonic
acid of the blood.

The alkaline phosphates of plasma, which are capable of con-
version into acid phosphates by association with carbonic acid, were
again erroneously credited with too much importance (Fernet).
We saw in fact (p. 139) that the main part of the phosphoric
anhydride found in the ash of plasma is derived from combustion
of the lecithin and nucleo-alburums, and that normal plasma con-
tains only the merest trace of sodic phosphate (Sertoli).

On the other hand, according to the observations of Setschenow
and Torup, maximal importance in the fixation of carbonic acid
must be assigned to the globulins of the serum, which, by acting
as weak acids, are able to combine with the alkalies of the blood.
When the tension of carbonic acid increases, the globulins of the
alkalies are dis7ociated, and combine with the carbonic acid to
form carbonates ; when, on the contrary, the tension of carbonic
acid falls the globulins are again associated with the alkalie5,
leaving the C02 in the free state.

Since carbonic acid is also found in the corpuscles of the blood
in a readily dissociable form, it is probable that the combinations
of the globulins with the alkalies exercise the same office in the
corpuscles as in the plasma, in the dissociation of carbonic acid.
It should, however, be noted that the absorption of the latter, as
effected by the corpuscles, is, in comparison with absorption in the

VOL. I 2 c

386 PHYSIOLOGY CHAP.

serum, dependent to a much greater extent on the partial pressure
of the C02. According to Bohr, this fact depends on the capacity
of the haemoglobin to unite chemically not only with the oxygen,
but also with the carbonic acid. He further showed that this last
combination is in no way obstructed by the simultaneous combina-
tion with oxygen ; which leads us to suppose that the two gases
are fixed in two different portions of the haemoglobin molecule, i.e.
the oxygen in the iron-containing portion of the colouring matter,
the carbonic acid in the protein residue (Fig. 169).

According to Fredericq the non -coagulated venous blood of the
horse is capable of absorbing 71 '4 vols. per cent of carbonic acid,
while the mass of corpuscles from the same animal only absorbs

FIG. 169.— Curve of absorption of CO2, by 1-76 per cent solution of haemoglobin (dotted line), and
by one of 3'8 per cent (unbroken line) in relation to progressive increase of pressure. (Bohr.) The
pressure (in mm. Hg) is recorded along the axis of the abscissae ; the amount of CO2 (in c.c.)
absorbed by 1 grm. haemoglobin, along the axis of the ordinates.

49 -6 vols. per cent. It follows that the amount of CO2 fixed by the
plasma is greatly in excess of that fixed by the corpuscles.

The carbonic acid of the serum, according to the unanimous
results of Fredericq, Zuntz, and Alex. Schmidt, is about 86 per
cent of that contained in the whole of the blood. It is possible,
however, that in the process of defibrination, part of the carbonic
acid of the corpuscles may pass into the serum, and that under
normal conditions the gas content of the blood is divided in
different proportions between the corpuscles and the plasma.
Certain experiments of Hamburger show, indeed, that by merely
changing the amount of gases in the blood, some individual sub-
stances may pass from the plasma to the corpuscles, and from
the corpuscles to the plasma:

Another notable fact is, that by means of the Torricellian
vacuum, it is possible to extract from the blood the whole of the
carbonic acid which it holds in combination (Setschenow). From

xi EESPIKATOEY EXCHANGES 387

serum, on the contrary, with the simple vacuum, it is only possible
to extract one part, and the addition of a weak acid is required to
extract the residue, which is more stably combined, and is present
in the blood to the amount of 5-9 vols. per cent (Pfiliger). The
fact that this portion also is turned out, in vacuo, in the presence
of corpuscles, without adding acid, suggests that the corpuscles
contain substances that function as acids, and that these are
diffused into the plasma during the action of the vacuum, or that
th$ sodic carbonate of the plasma penetrates to the corpuscles.
Among the acids of the corpuscles the first place must be given to
phosphoric anhydride, which they contain in larger quantities than
the plasma; besides which the oxyhaemoglobin functions as an
acid, as was demonstrated by Preyer, since it is capable of liberat-
ing carbonic acid from its sodium combinations in vacuo.

In regard to nitrogen and argon, we must 'confine ourselves to
saying that these gases are found in the blood in amounts differing
little from those in which they are absorbed and dissolved by
watery fluids in the presence of atmospheric air. According to
Kegnard and Schloesing, about 0'04 vol. per cent of the 2 vols. per
cent of indifferent gases extracted from the blood are argon. The
opinion held by some that a small amount of free nitrogen is
developed during the oxidative processes of the nitrogenous
substances of the tissues, and is subsequently poured into the
blood, has not at present been confirmed by any incontrovertible
evidence. Regnault and Keiset found a slight increase of nitrogen
in expired as compared with inspired air. So, too, the nitrogen
extractible from venous blood is always somewhat greater than
that which can be extracted from arterial blood. Pettenkofer
and Voit gave an adequate explanation of these facts, on the
assumption that they depend on the swallowing of air with
the food, and on the absorption of the nitrogen contained in the
gases of the intestines.

VIII. Since both oxygen and carbonic acid are thus found in
the blood in the form of readily dissociable combinations (in
relation to variations of partial pressure), it is natural to conclude
that the gas exchanges which take place incessantly between the
blood circulating through the capillaries of the lungs and the air
contained in the pulmonary alveoli (external respiration) are
accomplished by a simple physical process of diffusion, regulated
by Dalton's law. They depend, i.e., on the difference of the partial
pressures of the said gases as contained in the fluid and gaseous
media, separated by permeable septa or membranes, formed by the
walls of the capillaries and the epithelial cells that line the alveoli.

The scientific demonstration of this theory involved a series of
researches, directed to the separate determination of the partial
pressures of the two gases in venous and in arterial blood, in order
to compare them with those of inspired and expired air.

388

PHYSIOLOGY

CHAP.

Ill older to determine the tension or partial pressure of the (X or GO._, of
the air (at 0° C., and mean pressure of 760 mm. Hg) it is sufficient to know

FiO. 170. — Pfli'ger's pulmonary catheter, modified by Ludwig.

its percentage composition. Since inspired air con-
tains 20-96 per cent of O2 and OO3 per cent of
OCX, the partial pressure of the O2=159'3 mm. Hg,
and that of the C02 = 0-228 mm. Hg. To deter-
mine the tension of the gases of expired air,
whether emitted from the trachea, or at a deeper
level where it bifurcates with the bronchi, it is
sufficient to determine the percentage composition
of the 0., and CO., in the air obtained during ex-
piration by an air-pump attached to a simple
sound, the end of which can be introduced more
or less deeply into the respiratory passages.

It is, on the contrary, difficult to determine
exactly tlie tension of the 02 and CO., of the cir-
culating blood, venous or arterial. Indirect methods
have to be employed for this purpose.

Pfliiger and Wolffberg, to determine the tension
of O., and C0.2 in venous blood circulating in the
pulmonary capillaries, devised the method of sound-
ing the lung by a very simple instrument, which
they called the pulmonary catheter (Fig. 170). It
consists of two elastic tubes, the finer of which is
inserted into the larger. The first has an open end,
intended to communicate with one of the bronchi,
from which air can be aspirated by means of the
Torricellian vacuum at the other end. The second
is closed, and terminates in a thin rubber balloon,
which can be easily inflated by a small bellows.

Having opened the trachea of a dog, the sound
is introduced into the bronchus leading to the
inferior left lobe of the lung ; the small terminal
vesicle of the external tube is then inflated, so that
it hermetically seals the bronchus into which it is
introduced, and makes the corresponding lobe of
the lung impervious to external air, which does
not appreciably disturb the respiratory movements of the animal. After
four to five minutes the air contained within the blocked lobe of the lung

FIG. 171. — Frederick's aero-
tonometer. The blood,
which is rendered inco-
agulable with peptone,
rises from the carotid in
tube (i ; spreads over sur-
face of larger tube c, where,
by diffusion, it is brought
into equilibrium of tension
with the mixture of gases
therein contained ; and re-
turns by the jugular vein
into the animal by tube b.
Tube c is covered with a
large tube R, within which
water at the temperature
of the animal's body is
kept continuously circu-
lating. The small lateral
tube t introduces the
artificial mixture of gases
into tube c at the com-
mencement of the experi-
ment. The thermometer
T regulates temperature
of water circulating in R
during the experiment.

xi RESPIRATORY EXCHANGES 389

is again in equilibrium with the tension of the gases of the venous blood
circulating in it. The air is then aspirated from the sound,, and its percentage
composition determined by Bunseii's method.

The values found for the CO2 and O^ tension indirectly indicate the
tension of these gases in the venous blood circulating in the capillaries of the
lungs.

The tension of the 02 and C02 of arterial blood is determined by means
of the so-called aerotonometers. The simplest form is that of Fredericq,
represented in Fig. 171. It consists of a glass tube, filled with a gaseous
mixture of known composition (10 per cent of 02, 5 per cent C02, and the
rest N), along the internal surface of which there is a constant flow of blood
from the carotid artery. During its passage through the tube, the tensions
of the blood-gases and^of the artificial mixture of gases are equilibrated.

By making the blood incoagulable through previous injection of pro-
peptone or albumose, and returning to the circulation by the jugular vein the
blood that left by the carotid, the experiment can be prolonged for a
considerable time (an hour or more), so as to be certain of having established
equilibrium of tension between the gases of the arterial blood and those
contained in the aerotonometer. The blood that flows through the instrument
is maintained at body temperature by means of an external glass jacket in
which water is circulated at the required temperature. When the experiment
is completed, the percentage composition of the mixture of gases in the
aerotonometer is calculated by the usual method, and the values obtained
express the partial pressure of the O.> and C(X of arterial blood.

The experiments on the tension of the respiratory gases have
not led to uniform results : they vary greatly even in the same
animals under slightly different conditions.

The following table gives the average values cited by F.
Schenck and A. Giirber in their Text- Book of Human Physiology
(1897), which all relate to experiments carried out on dogs: —

At 0° C. and 760
mm. Hg.

Inspired Air.

Expired Air.

Arterial Blood, i Venous Blood.

mm. HX-

mm. H-.

mm. H#. mm. H<,r.

Oxygen .

150

122

29'6

21-0

Carbonic Acid .

0-3

30

22-0

41-0

These data coincide perfectly with the theory which holds
the respiratory gas exchanges to be the effects of simple
diffusion, which causes the gases to pass from the point of greater
to that of less tension. In fact the tension of O9 is seen to
diminish from inspired to expired air, and from that to arterial
blood ; and the tension of C0.7 diminishes from venous blood to
that of expired air, and thence to that of inspired air. The
oxygen must therefore be absorbed by diffusion from the respiratory
passages into the arterial blood, while the carbonic acid must be
exhaled by diffusion from the venous blood into the respiratory
passages.

The results of Bohr's subsequent experiments do not, however,
agree with this theory. • With one of his special aerotonometers

390 PHYSIOLOGY CHAP.

he determined the tension of the gases in the circulating arterial
blood, and that of the expired air at the tracheal bifurcation.
He repeatedly found that the partial pressure of the carbonic acid'
of the blood was less, and that of the oxygen greater, than the
respective partial pressures of the two gases in expired air.

In some of Bohr's experiments, for instance, the partial pressure
of the O2 and C02 varies as follows : —

02 of arterial blood = 100-144 mm. Hg.

Og of expired air, at tracheal bifurcation . . = 95-130 „

C02 of arterial blood = 17-30

C02 of expired air, at tracheal bifurcation . = 35- 41 „

Against these results of Bohr, the objection that he did not allow
sufficient time for equilibrium of tension to be established between
the gases of the arterial blood and the artificial air contained in
the aerotonometer, has no weight, because in this air, before the
entrance of the arterial blood, the partial pressure of the 02 was
less, and that of the CO2 was greater, than after the experiment.
On the basis of these facts, which are opposed to the theory of
diffusion as the sole determinant of pulmonary gas exchanges,
Bohr puts forward the hypothesis that the walls of the pulmonary
alveoli function as a secreting gland, and that the cells that line
them are capable of actively absorbing oxygen and exhaling
carbonic acid, even against the laws of the diffusion of gases.

Fredericq in his latest work does not accept Bohr's conclusions.
He invariably finds the tension of oxygen in the arterial blood
to be less, and that of carbonic acid greater, than the respective
tensions of the two gases in alveolar air. But this (as Tigerstedt
has pointed out) does not contradict the phenomena observed
by Bohr. One single fact, determined under valid experimental
conditions to be irreconcilable with the exclusive theory of
diffusion, gives legitimate reason to suspect that other forces
intervene in the production of gas exchanges, and are capable of
accelerating the effects of diffusion, and even of acting in
opposition to its laws. The study of this interesting question
deserves to be pursued without prejudice, the more so as Bohr
has discovered another fact that appears to be of the utmost
importance. After collecting and analysing the gases contained in
the swim-bladder of certain fishes caught at a great depth, he
found them to contain as much as 80 per cent oxygen. On
puncturing and emptying the swim-bladder, he found that it filled
anew with oxygen, but only on condition that the nerve plexuses
leading to it were spared. Once this fact is admitted, the
legitimate conclusion must be that the cells lining the swim-
bladder (which may be regarded as a modified lung) function as
glandular elements secreting oxygen under the influence of the
nervous system, and contrary to the laws of diffusion ; just as the

xi KESPIRATOKY EXCHANGES 391

salivary cells, in obedience to nervous impulses, secrete saliva in
defiance of a counter-pressure greater than that of the arterial blood
circulating in the gland (Ludwig).

Haldane and Smith (1896) investigated the tension of oxygen
in the pulmonary blood by a method applicable to man. The
method is based on the fact already demonstrated by Haldane in
1895, that with simultaneous action of oxygen and carbonic oxide
on the blood, the amount of the carbonic oxide fixed by the blood
is. proportional to the oxygen tension, so that it is possible from
the degree of absorption of carbonic oxide in the blood to calculate
the tension of the oxygen present. If a man or other animal is
made to breathe a gaseous mixture containing a small quantity
(exactly determined) of CO for a time long enough to make the
carbonic oxide content constant in the blood (measuring it at
intervals by small samples of blood taken from the subject), it is
possible from the degree, thus measured, of fixation of CO by the
blood, to calculate the 02 tension that prevails in the pulmonary
blood. It results from these experiments that the O2 tension
in the blood of a man's lungs amounts to 26'2 hundredths of an
atmosphere equal to 200 mm. Hg, a figure that is inexplicable on
the hypothesis of simple gas diffusion as the cause of the absorption
of oxygen in the lung. Identical results were obtained from
experiments on birds and mice (1897), by means of which these
authors were also able to show how want of oxygen acted as a
stimulus to tjie active absorption of this gas by the pulmonary
epithelium.

With regard to the process of the elimination of C0.7 from the
lungs in the air of the pulmonary alveoli, Grandis (19130) called
attention to a new factor which had till then escaped the notice of
physiologists.

It is known that in addition to C02, a considerable amount of
water-vapour is eliminated by the expired air from the blood
plasma circulating through the lung (according to Loewy, alveolar
air contains about 6 per cent of aqueous vapour). The blood
accordingly undergoes a temporary increase of concentration
during its passage through the lungs, which, by raising the C02
tension, must facilitate its expulsion into the alveolar air.
Grandis confirmed the importance of this fact by certain experi-
ments in vitro, in which he artificially increased the concentra-
tion of the blood, by adding strong solutions of sodium chloride
and sugar, with the effect of a prompt rise of tension in the gases
of the blood.

On the ground of these experiments he thinks it probable that
in living animals also the greater concentration of the blood, on
evaporation of the water in the pulmonary alveoli, must facilitate
the expulsion of C02. JThe experiments of Grandis, however, show
that the greater concentration of the blood raises the tension, not

392 PHYSIOLOGY CHAP.

only of the C02, but also of the 02, and thus can have no appreciable
value as a factor in the pulmonary gas exchanges — seeing that if
on the one hand it facilitates the elimination of C02 from the
blood, it checks the absorption of O2 on the other.

Another question indirectly connected with the nature of the
pulmonary gas exchanges, is that which refers to the influence
which is, or can be, exercised upon them by the nervous system.

At the end of 1892, Henriques demonstrated experimentally
in rabbits and dogs that stimulation of both vagi might cause
variations in the respiratory gas exchanges of the lungs. These
experiments were taken up by Maar in 1902, and extended both
to cold-blooded animals (tortoises) and to the warm-blooded
(rabbit). He endeavoured to define the precise effect of section
and artificial stimulation of the vagus and sympathetic upon the
pulmonary gas exchanges. The experiments on cold-blooded
animals led to the conclusion that absorption of oxygen by the
lungs was under the influence of the nervous system, the vagus
containing both nerve fibres that increase the absorption of
oxygen, and also other fibres that dimmish it. The former run to
the lung of the opposite side, the latter to that of the same side.
It was found impossible to establish any direct influence of the
sympathetic on respiratory pulmonary exchanges, nor did the
experiments on warm-blooded animals lead to any definite or
concordant results. The demonstration of a direct influence of
the nervous system on the pulmonary gas exchanges tells in favour
of Bohr's theory.

In speaking of recent work on this subject, mention must be
made of Krogh (1904), who studied the cutaneous and pulmonary
respiration of the frog, and came to the conclusion that cutaneous
respiration (which serves especially for elimination of carbonic
acid) is independent of the nervous system, and can be explained
on purely physical grounds (gaseous diffusion), while pulmonary
respiration (which particularly controls the absorption of oxygen)
is, on the contrary, effected principally by secretory processes of
the epithelium, and is regulated by the nervous system.

On the other hand, Loewy and Zuntz in their latest publication
(1904) still contend that the laws of diffusion adequately
account for the gas exchanges between the alveolar air and the
blood. They determined the velocity with which carbonic acid
traverses an excised frog's lung, and from this, taking into account
the varying thickness of the pulmonary walls, deduced the con-
ditions of gas diffusion in the human lung. They conclude that
the conditions of diffusion for the passage of oxygen from the
pulmonary alveoli to the blood, and thence to the tissues, are so
favourable that they ensure more than sufficient absorption of
oxygen, even in the most extreme cases of rarefaction of air com-
patible with life.

xi EESPIKATOEY EXCHANGES 393

IX. We know very little as yet about the physico-chemical
processes which complete the gas exchanges between the blood
circulating in the aortic capillaries, and the living cells of the
tissues, by the agency of the interstitial lymph (internal
respiration).

It was formerly supposed that the transformation of arterial
into venous blood took place within the capillaries. But there are
well-ascertained facts which prove the blood, when extracted and
kept at body temperature, not to be the seat of any very energetic
oxidative phenomena. The oxygen it contains gradually dis-
appears, i.e. drawn arterial blood slowly becomes venous. On the
other hand, circulating arterial blood is known not to become
venous along the entire course of the aortic system, but only when
it is passing through the capillaries. This fact was explained on
the hypothesis that the intermediate products of tissue consumption,
which reach the arterial blood by the capillaries, consisted of
reducing substances, i.e. are avid of oxygen, which they rapidly
subtract from the oxyhaemoglobin. This supposition is no
longer admissible, since it has been demonstrated that only the
erythrocytes, not the blood plasma, nor the lymph of asphyxiated
animals (in which there must be an accumulation of many
reducing substances), are capable of chemically combining with
oxygen. Neither the blood plasma, then, nor the lymph, contain
reducing substances, since the latter do not pass into these fluids,
but arise in the living cells of the tissues which breathe in virtue
of their metabolism, i.e. they take up oxygen and give otf carbonic
acid. It is therefore evident that the tissues are the seat of
internal respiration, and if the blood also breathes, however slowly,
this is in virtue of the mass of corpuscles which it contains, and
by which it functions as a tissue.

Many direct proofs might be adduced as to the correctness of
this theory. When fragments of living tissue, particularly of
muscle, are dissolved in drawn arterial blood or in a solution of
oxyhaemoglobin, a rapid reduction follows, by which the oxyhae-
moglobin is promptly converted into haemoglobin in that portion
of the fluid which immediately surrounds the fragments (Hoppe-
Seyler). If benzylic alcohol or salicylic aldehyde are added to
the arterial blood drawn from the vessels, it does not oxidise to
any appreciable extent ; if, on the other hand, this blood, plus one
of the above substances, is circulated in the vessels of organs
recently extracted from a living animal (kidney or lung), consider-
able quantities of benzoic or salicylic acid are at once produced
by oxidation (Schmiedeberg). The oxidation performed by the
isolated surviving organ seems due to the action of special enzymes
contained within the cells of the tissues (Schmiedeberg, Jacquet,
Buchner).

All tissues breathe (Paul Bert), but it is particularly in muscle

394 PHYSIOLOGY CHAP.

that the oxidising processes acquire a greater degree of intensity,
and have been most studied. Active muscle breathes in excess of
resting muscle. Blood coming from the vein of a tetanised muscle
is dark in colour, and contains a minimal amount of oxyhaemo-
globin ; while the blood which comes from a muscle that is resting,
or paralysed by section of its motor nerve, presents the normal
characters of venous blood, in which — as we have seen — the oxygen
content may exceed 15 vols. per cent of the blood.

Again, when muscle is placed under conditions that prevent it
from absorbing oxygen, e.g. when it is brought into an atmosphere
of hydrogen or nitrogen, it continues to give off carbonic acid, and
for a certain time is capable of contracting (Hermann, see p. 68).
It would thus seem that muscle must be allowed the property of
taking up and storing oxygen in such a condition that it cannot
be removed by simple lowering of pressure. The oxygen required
for the formation of carbonic acid, given off by muscle in the
presence of nitrogen and hydrogen, is certainly derived from that
previously stored up and fixed in a compound similar to, but more
stable than, that into which it enters with haemoglobin,' and which
has been wrongly termed intermolecular oxygen.

According to recent work of Verworn, Baglioni, and H.
Winterstein (1900-1907), the tissue whose vitality is most strictly
associated with the action of free oxygen is the central nervous
system. Baglioni, e.g., found on isolating the frog's spinal cord
from the body after cutting out the circulation, and taking as the
index of its activity the reflex movements of a posterior limb,
connected with the cord by the sciatic nerve, that the reflex
activity of the cord is in strict ratio with the O9 tension of the
surrounding atmosphere. If placed in a moist chamber, through
which nitrogen is passed without a trace of oxygen, such a spinal
cord at a temperature of 15-20C 0. ceases to exhibit reflexes after,
half to three-quarters of an hour. If it is then suddenly brought
back into the presence of oxygen, it recovers its vitality. On the
other hand, Baglioni succeeded in keeping alive the isolated spinal
cord of amphibia for a comparatively long period (forty-eight hours
and more) by placing it in a warm chamber through which pure
oxygen was circulated. This specifically high demand of the central
nervous system for oxygen explains the fact that in all cases of
asphyxia or lack of oxygen in tlie blood, the first tissue that feels
the toxic effects, and ceases its activities, is the central nervous
system (cerebral cortex, spinal cord ; see p. 70). We shall return
to this subject in Vol. III., in treating of the physiology of the
nervous system.

Moleschott enunciated the hypothesis that the oxygen passing
from the blood to the tissues is utilised in the constructive pro-
cesses, i.e. it enters into the most complex substances of the tissues,
which then, on splitting up, generate carbonic acid. Cl. Bernard

xi EESPIKATOKY EXCHANGES 395

also admits that " the oxygen combines in some way with the
tissues so as to constitute a provision for use when the animal is
unable to procure it from without." He based this assumption
particularly on the fact that muscle absorbs more oxygen during
rest, and spends more during activity, as though it accumulated
reserves to expend lavishly when need arises. Nothing definite is
known, however, as to the nature of the probable combinations
formed by oxygen with the different materials for building up
muscles and other tissues, or of the intermediate anabolic and
katabolic forms, through which it passes in combining with carbon
into carbonic acid. " The whole mystery of life," says Foster,
" lies hidden in the story of that progress, and for the present we
must be content with simply knowing the beginning and the
end."

We know that carbonic acid is one of the ultimate products of
the katabolic processes, and that the variations in the amount
formed and eliminated by the tissues are, as Fano says, an
expression " of corresponding changes in the course of the
destructive processes. The assimilated oxygen 011 the contrary
enters, at least in part, into the molecular structure of our tissues,
is included in the series of synthetic processes, and may partially
be considered #s an element which contributes to the anabolic or
constructive processes." We shall return to this argument in
treating of the metabolism or material exchanges of the body as a
whole.

In regard to this subject of the respiratory gas exchanges
between the blood and the tissues, the facts observed by Pfliiger
and Strassburg, to the effect that the lymph, serous fluids, and
certain secretions (bile, urine, saliva, milk) formed within the
living tissues contain merely a trace of oxygen, and a comparatively
large amount of carbonic acid, are very remarkable. These authors
conclude that 02 tension is low or practically nil in the tissues,
while the C02 tension on the contrary is high.

The high tension of carbonic acid that prevails, according to
recent researches, in living tissues is of especial significance,
because it facilitates the dissociation of oxygen from oxyhaemo-
globin, and thus places at the disposal of the tissues the maximum
possible amount of the oxygen received from the blood. Bohr,
Hasselbach, and Krogh (1904) found that on bringing dog's blood, in
vitro, at 38° C. into the presence, simultaneously, of 02 at low tension
(5 mm. Hg), and of C02 at various tensions, the blood absorbs a
less degree of 02 than when it is in presence of 02 alone, and that
the decrease in absorption is proportional to the amount of CO2
simultaneously present. ' This influence is much less felt if the O2
tension is progressively raised, as is clearly shown on the diagram
(Fig. 172).

The physiological value of this fact will be readily appreciated.

396 PHYSIOLOGY CHAP.

Since the tension of the carbonic acid constantly increases with
the passage of the blood into the aortic capillaries, this must
facilitate the dissociation of oxygen, and increase its concentration
in the blood plasma, so that it can be easily absorbed by the
endothelia of the capillaries and the tissue cells. The increase in
tension of the carbonic acid partly compensates for the diminished
concentration of oxygen in the plasma due to its consumption by
the tissues. This regulation is of especial importance in asphyxia,
when the oxygen of the blood is much attenuated.

On the other hand the high tension of carbonic acid in the
pulmonary capillaries does not in any way diminish the absorption

40 50 60 70 80 00 100 110 120 130 140 150

Fin. 17-2. — Curve showing influence of varying quantity of COo on absorption of oxygen at different
pressures, from delibrinated dog's blood at 88° C. (Bohr, Hasselbach, and Krogh). The
percentage amount of oxygen absorbed is marked on the axes of the ordinates ; the different
pressures of oxygen in mm. Hg, on the axes of the abscissa, while the different pressures of
CO-> acting simultaneously in the pressure of biood, are indicated above the respective curves.

of oxygen, for which, as has been shown, the influence of carbonic
acid becomes negligible in the presence of high oxygen tensions.

This fact suffices to explain on a simple process of diffusion
the gas exchanges between the blood and the tissues, by which
the latter continually absorb oxygen and give off carbonic acid,
converting arterial into venous blood. The data in regard to
external respiration, do not, however, preclude the probability that
the physical laws of diffusion may, in the case of internal
respiration also, be modified by the activity of the cells which
build up the walls of the capillaries.

X. We have seen that Lavoisier conceived of respiratory
chemistry as a slow double combustion of carbon and hydrogen
by which are formed carbonic acid and water. He was the first to
show that the amount of O2 absorbed exceeds that of the C02
exhaled, from which fact he deduced the formation of water.

xi RESPIKATOKY EXCHANGES 397

The gas exchanges of respiration are, however, more complicated,
as is readily seen on examining the changes induced in external
air by animal respiration.

Expired air, in comparison with inspired air, presents the
following differences :—

(a) It contains 5 vols. per cent less of oxygen (according
to Vierordt 16*033 vols. per cent instead of 20*95 vols. per cent).

(6) It contains a considerable amount of carbonic acid (from
3;3-5'5 vols. per cent, according to Vierordt).

(c) According to Regnault and Reiset, and Seegeii and Nowak,
expired air contains a slight excess of nitrogen, but whether this
is a waste product from the tissues owing to decomposition of
protein is doubtful, as already stated ; more probably it comes
from absorption in the blood of the excess nitrogen contained in
the intestinal gases.

(d) It contains traces of free hydrogen, of marsh gas, of
ammonia, and of other gases of hitherto unknown composition.
It is certain that these substances arise partly from the absorption
of intestinal gases, partly from exhalations of putrefactive excreta
that clog the skin and integuments (Hermann, 1883), partly from
pulmonary exhalations which when collected and condensed in
sterilised water, and inoculated subcutaneously, have a toxic
action (Brown-Sequard and D'Arsonval). Eormanek has recently
(1900) occupied himself exclusively with the question of the
toxicity of expired air. He found that air passed by the method
of Brown-Sequard and D'Arsonval through cages of animals
contained a really toxic substance, which was identified with
ammonia. This ammonia was not, however, derived from, the
expired air, but from the decomposition of urine and faeces within
the cages. When this source of impurity was eliminated, expired
air was obtained which had no toxic action. Formanek concluded
that no toxic substances were developed in the lungs of man and
other healthy animals. The sense of malaise which sensitive
persons experience in crowded rooms must arise reflexly, from
disturbance of thermal regulation, or the respiration of foul-
smelling substances.

(e) The expired air is saturated or nearly so with the aqueous
vapour exhaled along the respiratory passages.

(/) It is partly deprived of the dust, and the germs or
sporules that are never absent from inspired air, and which are
arrested all along the respiratory tract by the moisture of its walls
— these being clothed with vibratile epithelia, whose function is
to expel them, along with the mucus secreted by the muciparous
cells.

(</) Its temperature is approximately that of the body
(35-36° C.), consequently its volume when it issues from the
respiratory passages exceeds that of the inspired air, to which the

398 PHYSIOLOGY CHAP.

aqueous vapour with which it is saturated also contributes.
When the expired air is again reduced to the temperature and
degree of moisture of that inspired, it presents in relation to the
latter a slight diminution of volume, as first noted by Lavoisier
(1777).

The chemical composition of expired air varies between
sufficiently wide limits, not merely in different classes and species
of animals, but also in the same individual under different external
and internal conditions, according to the frequency and depth of
the respiratory movements. The slower and deeper these are, the
greater will be the output of carbonic acid and intake of oxygen.
The first portions of air given off in a respiratory act, which come
from the more superficial bronchial passages, contain less carbon
dioxide and more oxygen, in comparison with the later portions of
expired air, which come from the deeper bronchial tubes and the
alveoli.

It is obvious that the more perfect the pulmonary ventilation
consequent on the deepest respiratory acts, the more rapid and
abundant will be the gas exchanges, and therewith the emission of
carbonic acid and absorption of oxygen in the time unit. Ex-
perience, however, shows that increased pulmonary ventilation
does not merely increase the gas exchanges, which would be a
temporary effect, but also increases the formation of carbonic acid,
i.e. the absolute quantity which is expelled in the unit of time.
This phenomenon depends on the fact that increased pulmonary
ventilation exacts more, work from the respiratory muscles, and
naturally determines an increase of combustion and thus of
carbonic acid production.

When a known volume of oxygen is converted by combustion
into carbonic acid, the original volume of gas is not altered.
Since, however, in respiration the volume of oxygen absorbed
exceeds that of carbonic acid exhaled, it follows that a greater
or less amount of oxygen must be applied to other oxidative
purposes. Among these, besides the combustion of hydrogen by
which water is formed, must be reckoned the combustion of
sulphur to form sulphates, and of phosphorus, which forms
phosphates.

The ratio between the volume of carbonic acid exhaled and
the volume of oxygen absorbed is known as the respiratory

CO
quotient. This quotient, expressed by the formula ~ 2, is generally

lower than 1, and varies considerably in the different classes of
animals, and even in the same individual, according to the nature
of his food.

In the combustion of the different food-stuffs outside the body
a different quantity of oxygen is required according to the
different chemical constitution of their molecules. Thus, each

xi KESPIEATOKY EXCHANGES 399

molecule of the substances comprised in the carbo-hydrate group
contains oxygen enough to convert the whole of the hydrogen into
water. Accordingly for their complete combustion the only
oxygen required is that necessary for conversion of the carbon
into carbonic acid. Hence the volume of CO., formed is perfectly

CO
equal to the volume of 02 consumed, the quotient Q 2 = 1.

For the perfect combustion of fats and proteins, on the
contrary, more O.7 is required, since in their molecules there is not

CO
enough O0 to convert all the H2 into water. The quotient -~- a

is therefore less than 1. In the complete combustion of fats, the
quotient =0'7l ; in the complete combustion of proteins = 0'78.

It follows that if the substances introduced as food were
oxidised exclusively within the body, the respiratory quotient in a
pure carbohydrate diet would be = 1, in a fatty diet = 0-71, in a
protein diet=O78. But since not only do the food-substances
introduced into the body share in its oxidative processes, but the
various tissue-forming substances also take part, it seldom happens
that the respiratory quotient rises to 1, i.e. for the most part
it is represented by a variable proper fraction. It is only
under special circumstances that the respiratory quotient may
temporarily attain the value of 1, or even exceed it, as when fats
are formed from carbohydrates in the body, or when there
is a rapid diminution in the oxygen ,content of inspired air
(Rosenthal, 1902). An apparent increase of the quotient may
appear in certain birds in whose crop there is fermentation of the
food stored there, with production of C02.

It is a very interesting fact that the respiratory quotient
oscillates with the substances that predominate in the food : in a
diet mainly composed of starch the value rises to 0'9 ; in a diet
that is chiefly fatty it drops to 0*55 ; while lastly, in a diet
mainly consisting of meat it attains an intermediate value of
0*7-0'65. In an ordinary mixed diet the respiratory quotient is
about 0-8.

When we consider the metabolism or material exchanges of the
body as a whole, we shall examine the importance of these and
other facts relating to the oscillations of the respiratory quotient ;
we shall discuss the different methods employed for animals, or
man, in the study of the absolute magnitude of the respiratory
gas exchanges ; we shall see that this magnitude changes with age,
sex, constitution, external* temperature, work or rest, the different
hours of the day or night, etc. These investigations obviously
exceed the limits of the physiology of the respiratory apparatus, and
involves the functioning of the body as a whole.

400 PHYSIOLOGY CHAP.

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Heart of Limulus. Amer. Journ. of Physiol., 1905-1906, xv. 371-386.
H. M. VERNON. The Conditions of Tissue Respiration. Journ. of Physiol.,

1906-1907, xxxv. 53-87, and 1907-1908, xxxvi. 81-92.
J. BARCROFT and W. E. DIXON. The Gaseous Metabolism of the Mammalian

Heart. Journ. of Physiol., 1906-1907, xxxv. 182-204.
W. A. OSBORNE. The Haldane-Smith Method of estimating the Oxygen Tension

of the Arterial Blood. Journ. of Physiol., 1907-1908, xxxvi. 48-61.
J. BARCROFT. Differential Method of Blood-Gas Analysis. Journ. of Physiol.,

1908, xxxvii. 12--24.
J. BARCROFT and M. CAMIS. The Dissociation Curve of Blood. Journ. of Physiol.,

1909-10, xxxix. 118-142.
J. BARCROFT and FF. ROBERTS. The Dissociation Curve of Haemoglobin.

Journ. of Physiol., 1909-10, xxxix. 143-148.
J. BARCROFT and W. 0. R. KING. The Effect of Temperature on the Dissociation

Curve of Blood. Journ. of Physiol., 1909-10, xxxix. 374-384.
J. BARCROFT and FF. ROBERTS. Improvements in the Technique of Blood-Gas

Analysis. Journ. of Physiol., 1909-10, xxxix. 429-437.

VOL. I 2 D

CHAPTEE XII

MECHANICS OF RESPIRATION

SUMMARY. — 1. Historical. 2. Glandular structure of the lungs. 3. Conditions
of the lungs and other viscera within the thorax ; passive movements due to
variations in the negative thoracic pressure. 4. The thoracic cavity : changes of
form and dimensions with inspiratory and expiratory movements. 5. Muscular
mechanism of inspiratory and expiratory movements. 6. Normal and forced
respiration. 7. Accessory or concomitant respiratory movements. 8. Ventilation
or renewal of pulmonary air (spirometry), and respiratory pressure in the air-
passages (pneumatometry). 9. Respiratory displacement of the lungs, and
acoustic phenomena of percussion and auscultation. 10. Respiratory variations
of intra-thoracic and intra- abdominal pressure. 11. Respiratory variations of
pressure in the vena cava. 12. Respiratory variations of aortic pressure.
13. Effect of respiratory mechanics on the circulation of the blood. 14. Special
forms of respiratory movements. Bibliography.

IN order that the respiratory gas exchanges may be adequate for
the needs of ordinary life, it is essential that the air contained in
the alveoli of the lungs should be constantly renewed. A slow but
continuous replacement of alveolar air occurs by diffusion with
the air contained in the respiratory tract, which is, as we have
seen, persistently richer in oxygen and poorer in carbonic acid,
from the small to the large bronchi, and from these to the trachea.
This renewal by diffusion is facilitated by the gentle impacts given
to the lungs by the rhythmical movements of the heart (cardio-
pneumatic movements, as discussed in Chap. VII. 10). During the
physiological lethargy of hibernating animals, and in the profound
cataleptic state of apparent death produced under certain morbid
conditions, or by hypnotic influences, such as are employed by the
Indian fakirs, this occult and silent renewal of the pulmonary air
may suffice to maintain life for a long time, since the physiological
need of respiration is extraordinarily reduced. But under normal
conditions there is a crying want for more energetic replacement
of the air by a real pulmonary ventilation, produced by the
alternate rhythmical expansion and retraction of the thorax, in
which the lungs are hermetically enclosed — these organs being
eminently elastic, and yet capable of passively following the
thorax when it acts as a suction and a pressure pump.

I. The simplest and most fundamental experiments on the

402

CHAP, xii MECHANICS OF KESPIKATION 403

mechanics of respiration are those of Galen (A.D. 131-203). He
was the first to assert that the lungs passively followed the
movements of the thorax, but he assumed that there was a layer
of air between the pulmonary walls and the thorax.

Oribasus (A.D. 360) was the first who noticed the collapse of
the lung in double pneumothorax, and Vesalius (as we have seen,
p. 371) the first who employed artificial respiration by a bellows
inserted into the opened thorax to maintain life.

Malpighi( 1661) first described the structure of the lungs. Alfonso
Borelli (1679) first formulated a complete theory of the mechanism
of pulmonary ventilation. To Haller (1780) belongs, however, the
merit of explicitly denying that the pleural cavity contains air — a
notion which manyolung to, producing not a little confusion of ideas.
He further asserted the absolute passivity of the movements of
the lungs, which some of the earlier physiologists regarded as the
primum movens of pulmonary ventilation, while others after him
(Eudolph, 1821 ; Laennec, 1819) still believed, on the strength of
fallacious or wrongly interpreted observations, that the lungs
were capable of active movements independent of the thorax.

The exact determination of the muscular mechanisms that
govern the alternate acts of inspiration and expiration, and the
right appreciation of their functional value in normal (eupnoea)
and abnormal (dyspnoea) respiratory rhythm, is still the subject of
innumerable controversies, as we shall see in the course of the
present chapter.

II. We must leave the full description of the structure of the
lungs and air-passages, i.e. the trachea, and the large and small
bronchi which lead to the alveoli (where, as we have seen, the gas
exchanges between air and blood are carried on), to text-books of
anatomy and histology ; it is sufficient here to remark that from
the physiological point of view they may be regarded as large
branching glands lined with mucosa, in which the ramified
bronchial tubes represent the excretory canals, and the infundibuli
divided by internal septa into alveoli, or terminal air-cells of
somewhat polygonal form, the secreting glands. These air-cells
are lined with a single layer of cells, which are characterised by
their reduction to thin laminae, some nucleated, others non-
nucleated, which accounts for their secretory activity being
reduced to a minimum, as suggested tentatively in the previous
chapter, or entirely wanting, as held by the great majority of
physiologists. In immediate contact with the alveolar epithelium
is the network of pulmonary capillaries, with exceedingly fine
meshes, in the centre of which lies the denser and nucleated part
of the epithelial cells, while the more attenuated marginal cells,
which are reduced to a delicate lamella, invest the surface of the
capillaries facing the alveoli, so that the capillary network and
the epithelium which lines them internally form but a single layer.

404 PHYSIOLOGY CHAP.

Each infundibulurn is surrounded by connective tissue, rich in
elastic fibres, and containing blood and lymph vessels. A certain
number of infundibuli, with their respective bronchioles, inter-
connected by connective and elastic tissue, and by larger
vessels, make up the pulmonary lobules, provided in their turn
with lobular bronchi, which arise from the junction of the
bronchioles. A number of these lobules, united by the said
tissues, by still larger vessels, and by lobar bronchi, form the
pulmonary lobes which in conjunction make the lung.

The structure of the respiratory passages changes gradually
from bronchioles to lobular bronchi, from these to the lobar
bronchi, from the larger bronchi to the trachea. We must confine
ourselves to stating that the bronchioles are lined with a single
layer of cubical, non-ciliated, epithelial cells, surrounded with a
thin sheath of connective and elastic tissue, sparsely provided
with smooth muscle fibres. The epithelium of the lobular bronchi
is cylindrical and ciliated, and the tube consists of an external
sheath of connective tissue, rich in elastic fibres and concentrically
arranged smooth muscle cells. In the interlobular 'and lobular
bronchi the tube is more muscular and somewhat rigid, because
the coat of elastic and connective tissue, found on the outside of
the circular muscular layer, contains small irregularly distributed
plates of hyaline cartilage. These cartilage plates become larger
in the direction from medium to greater bronchi, while the
transverse layer of muscle diminishes. The mucosa thickens
from small to large bronchi. The epithelium is stratified (three
or more layers of cells) ; between the cylindrical ciliated cells
mucous goblet cells are occasionally visible. Beneath the epithelium
is a reticulated adenoid tissue with thin elastic fibres, and on the
outside a compact and conspicuous elastic layer, formed of the
predominantly longitudinal fibres, which are arranged in a
network, in which are many small mucoid and acinous glands,
opening into the lumen of the bronchus by small ducts that
pierce the elastic layer, reticulated tissue, and epithelium. The
mucous secretion of the goblet cells and small glands intercepts
the solid particles introduced with the air, while the cilia drive
the mucus with the agglutinated particles towards the trachea
and larynx.

The tracheal tube is much more rigid, since the elastic sheath
is more external and tougher, and contains rings of hyaline
cartilage, interrupted at the back and completed by bundles of
smooth muscle fibres, stretched transversely across the ends of
the cartilage, while a few other muscle bundles run longitudinally
outside the former. The tracheal mucosa is not essentially
different from that of the greater bronchi, and contains more
mucous glands. The strong elastic layer adjusts the mucosa to
the longitudinal alterations of the tube, keeping it tense and

xii MECHANICS OF EESPIEATION 405

smooth. The smooth muscle cells found along the air-passages,
and most abundantly in the smallest bronchi, are able, according
to the degree of their tonus, to alter the lumen of the canal as
required.

III. The lungs of the foetus are void of air (atelectatic), and
therefore sink (in the test known as docimasia hydrostatica) when
immersed in water. The first respiratory movements which
occur after birth expand the alveoli of the lungs and fill them
with air, and lungs removed from any individual who has already
breathed float on the surface of water in docimasia hydrostatica,
because the elastic retraction they undergo when the thorax is
opened is not strong enough to expel all the air from the alveoli.
This is because the capillary bronchi or bronchioles (which, as we
have seen, contain no cartilaginous platelets such as give a certain
rigidity to the larger bronchi) collapse, and hinder the complete
expulsion of the alveolar air. The lungs of a new-born infant,
which has already breathed, may after a certain time become
atelectatic again by the reabsorption of the air which they contain.
From the same cause the lungs of a man or other animal become
atelectatic in a few hours, if the pleural cavity has been opened on
one side.

The form and volume of the atelectatic foetal lungs correspond
exactly with the form and volume of the thoracic cavity in which
they are enclosed. They are in perfect elastic equilibrium, since
on opening the thorax they do not retract, and if a mercury or
water manometer is connected with the trachea so as to measure
the intrathoracic pressure (Bonders), it is found to be equal to
atmospheric pressure, the manometer showing no movement on
opening of the thoracic wall (Bernstein).

These conditions gradually alter during extra-uterine life. As
the thorax grows more rapidly than the lungs, these are thrown
into a state of increasing elastic tension, in proportion as the
difference between the capacity of the thorax and the volume of
the lungs increases, when they are respectively in the normal
position of equilibrium. This can easily be determined by Bonders'
method on the bodies of persons of different ages, provided they
did not die of pulmonary diseases. If a manometer is connected
with the trachea of a dead new-born infant, that had breathed, the
lungs do not retract, and the column of mercury does not rise, on
opening both pleural cavities; the same conditions, therefore,
persist after birth as in the foetal atelectatic lung (Hermann).
When, on the contrary, the same experiment is repeated on the
body of an adult, the lungs retract more or less according to age,
by elastic recoil, till they are in equilibrium with a column of
mercury of 5-7*5 mm. Accordingly, in the cadaveric, or the
passive respiratory position of the adult thorax, it is the atmo-
spheric pressure which acts within the pulmonary air-passages,

VOL. I 2 D a

406 PHYSIOLOGY CHAP.

and cannot act upon the surface of the lungs (these being her-
metically enclosed in the thoracic cavity, formed mainly of rigid
walls), that determines the passive distension as well as the,
elastic tension of the same, and the negative pressure within the
thoracic cavity in the expiratory position.

Normally the thoracic cavity is completely filled by the lungs,
which adapt themselves perfectly to its conformation. The two
layers, visceral and parietal, of the pleura, are in immediate
contact, separated only by the thinnest stratum of lymph, which
facilitates the gliding of one over the other. The pleural cavities
are potential only : under morbid conditions they are formed by
the liquid or 'solid exudation that is poured out between the two
layers ; or by a unilateral or bilateral, external or internal, aperture
in the same. The rapid death by asphyxia in double pneumo-
thorax shows the passivity of the lung movements, owing to which
ventilation or renewal of the air essential to the life of the animal
ceases. When, however, from the partial or complete occlusion
of the opening, the air cannot freely enter or leave the pleura!
cavities, the lungs are still able to distend ; this explains why in
many cases of perforation of the thorax the respiratory gas
exchanges are not profoundly modified.

Besides the lungs, the thoracic cavity also contains the heart
with the large venous and arterial trunks, which, as hollow organs,
indirectly feel the effects of the atmospheric pressure acting
directly upon the extrathoracic vessels that communicate with the
heart. Intrathoracic negative pressure accordingly determines
not merely the distension of the lungs, but also that of the heart
and intrathoracic vessels, in proportion with their capacity for
dilatation. The thick-walled ventricles of the heart, and the
arteries, which are always under strong internal pressure, feel
little or no effect from the negative intrathoracic pressure ; the
auricles and large trunks, on the contrary, which have thin walls,
and are not distended by positive internal pressure, suffer a certain
degree of expansion, by which the lumen is widened, and the
course of the blood from the extrathoracic to the intrathoracic
veins facilitated.

The oesophagus, as a hollow intrathoracic organ communicating
with the exterior, should dilate to a certain extent in consequence
of the negative pressure that obtains within the thorax ; its cavity,
however, is potential, and is only formed when the canal is
traversed by foreign bodies, such as food. Under ordinary con-
ditions the walls of the oesophagus are in contact, so that the
lumen is obliterated, and the negative intrathoracic pressure, far
from aspirating air into the canal, only makes the walls adhere
more closely, in consequence of the atmospheric pressure exerted
externally upon its intrathoracic portion. But if a hollow
sound is passed through the oesophagus, it is converted into

XII

MECHANICS OF KESPIEATION

407

an intrathoracic cavity communicating with the exterior, and
subject, like the lungs, to all the changes of intrathoracic pressure
(Luciani). The method of automatic registration of variations of
intrathoracic pressure by the oesophageal sound, which we intro-
duced into the experimental technique of physiology in 1877, is
based on this fact.

In conclusion it must be noted that the negative intra-
thoracic pressure also affects the soft movable portions of the
walls of the thorax, more particularly the diaphragm, by which its
floor is separated from the ab-
dominal cavity and the inter-
costal spaces. The former, as
well as the latter, are during
the expiratory position of rest,
and in the dead body, curved or
bent towards the thorax, where
pressure is negative, while they
are subjected externally to at-
mospheric pressure.

IV. Let us now consider the
changes in form and dimensions
exhibited by the thorax during
the alternate movements of ex-
pansion (inspiration) and con-
traction (expiration), which
compose the respiratory rhythm.

During inspiration the whole
thoracic cavity dilates more or
less, in its several diameters, in
proportion to the intensity of
contraction and the number of
muscles which come into play.

The dilatation of all the
horizontal diameters of the
thorax is the effect of the ' rais-
ing of the ribs, which, with the
vertebral column, with which
they articulate posteriorly, and the cartilaginous prolongations
and the sternum, to which they are united anteriorly, form the
skeleton or rigid system of the thorax.

The ribs, to the number of twelve on each side, constitute a
series of long, slender, arched bones, which start from the dorsal
vertebrae to extend outwards and forwards. They slant obliquely
from above downwards, so that their points of posterior articulation
are a little above the anterior end, which is united with the
sternum by means of the cartilaginous prolongations, directly
(first seven ribs) and indirectly (eighth, ninth, tenth ribs). The

FIG. 173.— Right half of thoracic skeleton.
(Spaltenholtz.)

408 PHYSIOLOGY CHAP.

two last ribs are loose, and are of less importance in the respiratory
mechanism (Fig. 173).

By means of a double articulation with two vertebral bodies
and with a transverse process, each rib is able to rotate round an
approximately horizontal axis, which passes along its neck, and
forms a greater or lesser angle with the horizontal plane. The
axes of rotation of the two corresponding ribs are convergent in
front, and decussate, forming angles that decrease, according to
Volkmann, from the first to the tenth rib (from 125°-88°). It
follows that in the upward rotation of the ribs, the point of the
costal arch which rises most, corresponds not with the anterior end
of the rib, but with a lateral point of the costal convexity, through
which passes a tangent parallel to the axis of rotation, as shown in
Fig. 174. And since the angle formed by the anterior crossing of
^ Q u , the axes of rota-

tion diminishes from
above downwards,
the point of maxi-
. mal rise' for the
/ different ribs in in-
spiration is displaced
and pushed more
towards the side, in
proportion with the
descent from the
first to the tenth
rib.

FIG. 174.— Horizontal projection of costal ring formed by 5th ribs. lhe increase 111

(Luciani.) ub and a'b' are the two axes of rotation of the nKlinnp fransMrarao

double costo- vertebral articulation, which cross, forming in L imlut!> irdllBVeise,

this case an angle of 70°. The tangent c', parallel to a'b', shows and anterO-pOSteriOr

the point of greatest elevation of the arch in inspiration. j . ,r .

diameter also varies

in the different costal hoops, becoming greater in proportion to the
inclination of the ribs, and to their length and curvature.

With the rise and forward inclination of the ribs the sternum
is also displaced, describing an arc of a circle from above down-
wards, and from behind forwards, in the vertical sagittal plane of
the thorax. Since this forward and upward displacement of the
sternum is least at its upper, and greatest at its lower end, it
follows that the different sections of the sternum must bend a little
towards each other, and the costal cartilages make a slight revolution
round their longitudinal axes.

In consequence of the inclination of the ribs and their elasticity,
the curvature increases when they rise to an approximately
horizontal position; on the other hand, at the junctions of their
anterior ends with the cartilages, the curvature becomes slightly
flattened, which induces a certain widening of the intercostal spaces,
proportional to the degree of their inclinations and respiratory

XII

MECHANICS OF EESPIKATION

409

elevation. According to Ebner, this dilatation is not perceptible in
the two first intercostal spaces, owing to the low inclination of the
first ribs and the minimal rise of the upper end of the sternum.

The inspiratory dilatation of the vertical diameter of the
thorax is not directly visible from without, as it is produced
by the descent of the diaphragm, but it may be estimated from
the rise in the upper end of
the abdominal wall, owing to
the displacement of the viscera
that occupy the diaphragmatic
concavity.

The inspiratory muscular
contractions which displace the
bones of the thorax from the
position of equilibrium are op-
posed 'by various resistances,
due to the weight of the parts
to be lifted, the elasticity of the
costo-vertebral ligaments of the
costal cartilages and bones, and
lastly to the elastic resistance
of the lungs which produces
negative intrathoracic pressure,
and the elastic resistance of
the gases in the alimentary
canal which work against the
downward movement of the
diaphragm. It follows that when
the inspiratory and dilating
mechanisms of the thorax cease
to work, the bones of the thoracic
cavity return spontaneously to
the mean position of equilibrium,
either from gravity or from the
elastic reaction of the ligaments,
cartilages, ribs, and lungs, as
well as of the stomach and in-
testines. We shall, however, see that the movements of expiration,
or retraction of the thorax, are always aided by expiratory muscular
contractions, which tend not only to bring the bones of the
thoracic cavity back into the position of equilibrium, but to force
them beyond this position by giving the ribs a twist from above
downwards, till in the forced or dyspnoeic respiration they reach
the maximal constriction of the thorax and diminution of its
several diameters.

V. Of the inspiratory muscles the diaphragm (Fig. 175) is of
the first importance, owing to its conspicuous action. By the

FIG. 175.— Lower half of thorax with four lumbar
vertebrae. (Luschka.) Diaphragm seen from
the front ; a, (ith dorsal vertebra ; It, 4th
lumbar vertebra ; c, ensiform process ; d, d',
aorta, which enters diaphragm by special
aperture ; e, oesophagus ; /, aperture in tendon
of diaphragm for passage of vena cava inferior ;
1, 2, 3, trilobate expansions of tendinous centre ;
4, 5, costal portions, right and left, of dia-
phragm muscle ; 6, 7, right and left crura of
diaphragm ; 8, 8, internal intercostal muscles,
which are absent near the vertebral column,
where it joins the external intercostals ; 9, 9,
10, 10, subcostal muscles of left side.

410

PHYSIOLOGY

CHAP.

contraction of its muscular fibres, which converge towards the
trilobate tendinous centre, the convexity towards the thoracic
cavity diminishes, pushing the abdominal viscera downwards.
According to Hasse (1880), during maximal inspiration the right
lobe of the tendinous centre descends 2'5 cm., the left lobe 2 cm.,
and the central lobe about 1 cm. The muscle fibres inserted in
the cartilages of the six last ribs contribute to the elevation and

expansion of the lower ribs,
since they are directed almost
vertically upwards, the vault
of the diaphragm being sup-
ported by the abdominal
viscera (Duchenne). The an-
terior muscle fibres, which run
more horizontally towards
the tendinous centre, oppose
a certain resistance to the
forward displacement of the
sternum. This may be the
reason why the sternum is
bent in patients who have
suffered a long time from
asthma (Thane). Nor is the
action of the diaphragm con-
fined to increasing the vertical
diameter of the thorax with
inspiration, as all admit. It
also (by aiding the elevation
and expansion of the false ribs)

Fin. iW.-Deei, and prevortebral muscles of neck. aSSlstS the dilatation of the

(Allen Thomson.) a, Superficial section of basilar transverse diameter of thebaSC
process ; b, transverse process of atlas; <•, p , •, , -, j j-r> ,v

transverse process of 7th cervical vertebra ; d, d', OI the tnorax, and modifies tllG

bodies of 1st and 4th dorsal vertebra; e, c', 1st omWIifipafinTi nf j-V,0 aon-iffo!

and 2nd ribs ; 1,2, rectus capitis anterior major amplification OI tne Sagittal

and minor; 3, 8', 3", median upper and lower diameter at the level of the
part of musculus lon^us colli ; 4, 4', 4", >I.

intertransversales ; 5, y scalenus anterior and its lower CllQ 01 the Sternum,
insertion on 1st rib; 6, 6' scalenus medius, and w j i~ • i» i 11

insertion on 2nd rib; V, scalenus posterior; 8, effects which are leSS Well

posterior part of levator scapulae ; !>, splenius known an(J are usually OV6r-

looked.

Other inspiratory muscles are the_ three i scaleni (Fig. 176),
which exert traction on the first two ribs, and Thus elevate and
maintain the entire thoracic wall (Duchenne).

The M. levatores costarurn longi et breves, twelve on each side,
are able from their insertion in the immediate vicinity of the
costo-vertebral articulations to produce an extensive elevation
in the anterior ends of the ribs on gentle contraction (Traube,
Kosenthal). The inspiratory action of the M. serratus posticus
superior is also evident.

XII

MECHANICS OF BESPIKATION

411

Since the direction of the fibres in the M. levatores costarum
and the M. intercostales externa (Figs. 177 and 178) coincide, it
is natural to regard these also as inspiratory muscles.

The function of the intercostal muscles, external as well as
internal, has, however, been a subject of endless controversy,
beginning with the lively polemic between Haller and Hamberger,
and lasting into our own day. The most varying and opposite
points of view have found strong supporters. Setting aside the
opinion of Galen and Bartholin, who reckoned the external
ihtercostals to be expiratory, and the internals inspiratory ; and
the view of van Helmont, Arantius and others who denied any

FIG. 177.— Intercostal muscles of 5th and 6tli spaces. (Allen Thomson.) A, Side-view ; B, back-
view ; IV, 4th dorsal vertebra ; V, 5Jbh rib and cartilage ; 1, 1, M. levatores costarum longi
et breves ; 2, 2, M. intercostales externa ; 3, 3, M. intercostales interni, as shown by
removal of externi in lower intercostal space. In A there are no external intercostals in
the intercartilaginous spaces ; in B there are no internal intercostals near the vertebral
column. ••

active function whatever to the intercostal muscles, and regarded
them merely as the complement of the thoracic wall, as well as the
opposite view of Mayow, Magendie, Burdach, etc., who held both
externals and internals to be alternately inspiratory and expiratory
in function ; there remain four other aspects of the question, which
are defended with conflicting arguments by distinguished physio-
logists, and are set forth in modern text-books : —

(a) Both external and internal intercostal muscles are in-
spiratory (Borelli, Senac, Boerhaave, Winslow, Haller, Cuvier,
Duchenne).

(b) Both kinds of muscles are expiratory (Vesalius, Diemer-
Brock, Sabatier, Beau and Maissiat, Longet).

412

PHYSIOLOGY

CHAP.

(c) The external intercostals are inspiratory, the internal are
expiratory, with the exception of the intercartilaginous portions
(Spigel, Vesling, Bayle, and Hamberger, Hutchinson, A. Fick,,
Martin, and Hartwell).

(d) The intercostals are of no great importance in regard to
the movements of the ribs ; they serve rather to regulate tension

FIG. 178. — Deep muscles of anterior wall of thorax, seen from behind. (Allen Thomson.) a,
Posterior part of manubrium sterni ; b, b, clavicle ; i-ix, anterior part of ribs and carti-
lages; 1, 1', M. sterno-thyroidei ; 2, 2', M. sterno-hyoidei ; 3, 3', M. triangulares sterni; 4, 4,
upper part of transverse muscles of abdomen which meet at 4' 4' of linea alba posterior ; 5,
insertions of diaphragm on lower ribs, crossing fascia of transverse muscles ; 5' bundles of
diaphragm inserted into ensiform process:; 6, 6', intercostales interni ; 7, 7, 7, intercostales
externi, exposed by removal of interni.

in the intercostal spaces, and to reinforce them during inspiration,
impeding their retraction by the increased negative intrathoracic
pressure (Henle, Meissner, Brlicke, von Ebner, Landois).

Criticism of these several theories would necessitate a prolonged
dissertation, disproportionate to the true importance of the
arguments and the scope of this text-book. Here we can only
summarise the facts that appear of most importance, and may
determine our choice among so many opinions.

xii MECHANICS OF KESPIKATION 413

It is incontrovertible that the direction of the fibres in the
external intercostals between two ribs is identical with that of the
levatores costarum, and that the shortening of any one fibre can
only occur, notwithstanding the extension of the intercostal space,
when both ribs are raised. On the other hand, it is a fact that the
fibres of the internal interosseous intercostals, which run in the
opposite direction, can only shorten when the intercostal spaces
are reduced by the lowering of the ribs. The tenability of this
view is apparent if we expose the intercostal muscles of the thorax
of a dead body, and imitate the inspiratory process, by drawing the
sternum upwards with a hook, introduced through a hole in the
maiiubrium. It will then be seen that as the intercostal spaces
widen, the external intercostal muscles relax, and the internal
interosseous intercostals contract ; this shows that during life the
insertions of the external intercostals come together during
inspiration, and those of the internal in-
tercostals separate.

Since the muscles shorten actively
during their contraction, and are passively
elongated by the action of the antagonists,
it follows that the external intercostals
must be inspiratory and the internal inter-
costals expiratory. Hamberger's schema
and machine (1751), however imperfect
and inadequate as an exact reproduction

Of the physiological prOCeSS, Still Serves to FIG. 179. - Hamberger's schema

olnm'rlaf-e» f"hp rnonTrim'nc: of tVn'c fanf fTTirr to demonstrate the functional

ICiaate tne mecnaniCb OI tniS laCt (± Ig. antagonism of internal and ex-

1*79). When the ribs ac and Id pass into ternal intercostals (reproduced

, '. . . . i T* j.i from Fig. -2 of his dissertation).

the inspiratory position ag and 67, the

intercostal space dilates (bh<ab) ; the sternum gf moves away
from the vertebral column al (bfj>be); the fibres of the external
intercostals ak shorten (ak>al), and those of the internal inter-
costals ck lengthen (ck<lg). The reverse occurs when the system
passes from the inspiratory position a b g f to the expiratory
position abed.

In regard to the inspiratory function of the intercartilaginous
muscles which form the anterior prolongation of the internal
intercostals, Hamberger's explanation is less convincing, but it is
intelligible by the help of the following schema (Fig. 180). When
the ribs are curved, they may be regarded as rods bent at an
angle acd and bef, in which the articular points c and e represent
the symphysis between the bony and cartilaginous parts on which
the traction is exerted. During inspiration the fibres of the inter-
cartilaginous muscles, which have the direction gli, move the
sternum df away from the vertebral column ab, like the fibres of
the external intercostals, which run in the direction kl. During
this, double action the angles c and e must get blunted, because the

414

PHYSIOLOGY

CHAP.

muscles of the upper intercostal spaces work simultaneously, and
the entire thorax is slightly elevated by the contraction of the
scaleni. It follows that both the external intercostals and the,
intercartilaginous muscles are active in the inspiratory position,
although they have an opposite course (gli^g'h', kl>k'l'). This
view of Hamberger's was better illustrated at a later time by
Hutchinson (1852).

It is supported as regards the inspiratory action of the external
intercostals by direct observations on the living. These muscles
have been observed on animals to become tense, and to harden and
thicken during inspiration, while during expiration they relax and
flatten (Antonio Marcacci, 1843 ; Duchenne, 1866 ; Kosenthal,

1882). When in the dog
or cat a section of the in-
ternal intercostal muscle is
exposed by care fully cut ting
away the external intercostal
that covers it, so that both
intercostal muscles, the ex-
ternal and internal of one
or two adjacent intercostal
spaces, can be simultane-
ously observed, an alternate
contraction of their fibres
can be detected — those of
the external intercostals
being active during in-
spiration, and those of the
internal intercostals during
expiration (Ant. Marcacci).

A f Q lofpv fimo tViia -0700
^-l a «tM=r timi Wd8

FIG. 180. — Schema to demonstrate that the function
of the internal intercartilaginous intercostals is
identical with that of the external interosseous confirmed bv trrapllic records,
intercostals. . 111 i

which showed that the

internal interosseal intercostals contract alternately with the
diaphragm, and therefore have an expiratory action (Newell-Martin
and Hartwell, 1879).

The experiments with localised electrical stimulation, which
proved to Duchenne and others that there was always a narrowing
of the intercostal space and elevation of the lower above the upper
rib, either when the external intercostals alone are stimulated, or
when the internal are excited as well, does not contradict the
above facts, since normally, in inspiration, all the external inter-
costals contract synergically, the thorax being lifted and supported
by the scaleni, which must necessarily cause distension of the
intercostal spaces.

The function of the intercartilaginous muscles, again, has been
experimentally confirmed. K. du Bois-Eeymond and P. Masoin

XII

MECHANICS OF EESPIEATION

415

found in dogs, cats, and rabbits that with forced respiration
the intercartilaginous muscles contract synchronously with the
diaphragm, i.e. are inspiratory, which was confirmed later on by
Bergendall and Bergmann. E, Fick
(1897) made an exhaustive in-
vestigation of the subject, both
critically and by means of vivi-
sections on dogs, and came to the
same conclusion.

Besides the internal interos-
seous intercostals, all the muscles
contained in the depth of the ab-
dominal wall act as inspiratory by ,
compressing the abdominal viscera,
thus pushing the diaphragm up-
wards and the lower ribs down-
wards. Such are the rectal
abdominal, the oblique external
and internal, and also the trans- ^

verse muscles. » ^

The instruments used in measuring
the different diameters of the thorax, FlG- 18L ~
and the variations which these undergo

J

during normal and forced respiration,
are known as thoracometers. That of

Sibson, represented in Fig. 181, is the

generally used, and i
apply.

most generally used, and is easy to

metal rods at a right angle, D is applied
to vertebral column, and B (which runs
along the graduated scale C) carries at
its extremity a toothed rod A, provided
with- a button to be applied to the
sternum. This moves an index, which
shows the excursions, magnified on a
dial.

If this instrument is reduced to the form of a measuring compass
(callipers), the limb A, which runs in a cogged wheel, and moves the
indicator of the dial, being replaced by a capsule covered with a rubber
membrane, kept taut by an elastic spring, and provided with a button, the

FIG. 182. — Marey's Pneumograph (latest model). Flexible steel plate, curved by the traction of
two arms of a lever joined at the circumference of the thorax by a silk band. The curve of the
plate is shown by a lever attached to the centre of the elastic membrane of an exploring
tambour. This records the pneumogram inversely upon a revolving drum, i.e. the descending
line corresponds with the inspiratory dilatation of the thorax, and the ascending line with
its expiratory retraction.

respiratory variations of any given thoracic diameter can be registered on a
revolving cylinder.

This is the model on which the thoracograph of Bert and of Fick, and
the stethograph of Burdon-Sanderson are constructed.

Marey's pneumograph (Fig. 182), of which there are various types, make&

416

PHYSIOLOGY

CHAP.

regular and measurable tracings of the variations of the thoracic circum-
ference. It is one of the instruments most employed for clinical purposes.

Eosenthal's phrenograph is used to obtain exact tracings of the excursions
of the diaphragm. It consists in a spatula-shaped lever, applied, aftef/
making an opening in the median line of the epigastrium, to the concave
vault of the diaphragm. A simpler method is that which introduces a flat
elastic rubber bag between the diaphragm and the abdominal organs, which
is: compressed when the diaphragm contracts, and decompressed on its
relaxation, these effects being transmitted to a Marey's writing tympanum
(Foster). This method records not only the movements of the diaphragm,

but also the alternate contrac-
tions of the abdominal muscles.
The simplest method, which
involves 110 vivisection, and is
therefore applicable to man,
consists in applying the button
of an exploring tympanum,
or of Vierordt's sphygmo-
graph, or of Burdon-Sander-
son's cardiograph (Fig. 107,
p. 267) to any point of the
epigastrium. In man (who,
as we shall see, breathes with-
out active intervention of the
abdominal muscles) this
method yields fairly satis-
factory results.

VI. After defining the
inspiratory and expiratory
muscular mechanisms, on
which depend the rhyth-
mical expansion and
contraction of the thor-
acic cavity, we next have
to determine which of
these intervene and have
a preponderating action
during normal respiration,

FIG. 183. — Diagram of variations of antero - posterior an(J wnicn come HltO

TV'

.

diameter of thorax and abdomen in the two sexes
during normal breathing and forced respiration, m lorCCd Or

respiratory rhythm.

Even in ordinary quiet breathing two types of respiratory
movements can be distinguished, the abdominal and the costal ;
in the former the activity of the diaphragm is the more pro-
nounced, in the latter that of the external in tercostals, or generally
speaking, of the muscles by which the ribs are elevated.

According to Hutchinson's observations (1852), a man's
breathing is always abdominal, a woman's costal. By drawing on
a flat plane the outline of the shadows projected by two persons
of different sex, at the several moments of normal or forced
respiratory movements, he obtained the diagrams of Fig. 183,
which illustrate very effectively the two types of respiration.

xii MECHANICS OF KESPIKATION 417

During inspiration and quiet expiration, the anterior profile of the
thorax and abdomen oscillate between the limits of the boundaries
of the black line nn '. It will be seen that this tract is deepest in
man at the level of the epigastrium, and in woman at the upper
region of the mammae. The excursion of the thoracic-abdominal
profile of maximal inspiration reaches the dotted line in the two
figures, and in maximal expiration it falls to the outline of the
same. It will be seen that during forced respiration there is no
longer the marked difference observed in quiet breathing, between
the variations of the sagittal diameter of the thorax in man and
woman. In both there is maximal costal dilatation and forward
displacement of the sternum during forced inspiration, and
maximal abdominal retraction in forced expiration.

According to Hutchinson, the difference between the normal
types of respiration in man and woman is not the effect of staysr
because this type of breathing is seen in girls who have never
worn them. Apparently it is a secondary sexual character, formed
in the course of phylogenesis as the effect of pregnancy, which
necessarily develops costal respiration, increasing intra-abdommal
pressure, and confining the action of the diaphragm. Many,
however, hold that the thoracic type of respiration is an effect of
the corset or ceiriture (Beau and Maissiat, Walsche, Sibson), and
A. D. Waller has put forward the same opinion, adducing the fact
that women of savage races, like the males, exhibit abdominal
respiration.

As regards the abdominal type of respiration in the male sex,
it is desirable to correct an .error that is widespread even in
modern text -books, to the effect that the diaphragm exerts a
preponderating influence over all the other inspiratory muscles.
A. Fick (1866) remarked that inspiratory movements can be pro-
duced on oneself, with a little practice, by throwing the diaphragm
only into action. This is most easily effected by associating the
idea of pressing the contents of the abdomen with the act of
inspiration. During this purely diaphragmatic inspiration, the
transverse and antero-posterior diameters of the thorax undergo
hardly any change, save near the base, where they are slightly
enlarged, although less than in normal costal breathing.
Fick affirms that only the sagittal diameter near the ensiform
process increases, and that the transverse diameter near the last
ribs diminishes ; but we have been unable on ourselves to verify
this last assertion. We have always found that pure diaphragmatic
breathing is far more fatiguing than normal respiration, the proof
being that man as well as woman normally breathes more with
the whole of the external intercostal muscles, which elevate and
extend the ribs, than with the diaphragm.

If we assume with Donders that the external surface of the
thoracic cavity covers some 20 dcm., and that this surface on an

VOL. i 2 E

418

PHYSIOLOGY

CHAP.

average increases only some 2-5 mm. on every side by the action
of the external intercostals, this still, according to Fick, yields a
volume increase of 500 c.c., which corresponds to the average
volume of normally inspired air. According, therefore, to Tick's
calculations, the diaphragm hardly takes any part in normal
inspiration, or at most the tonicity of its fibres is augmented,
in order to check any upward aspiration during the widening of
the thorax.

This theory is evidently exaggerated, and does not harmonise
with the fact that in the quiet breathing of man the maximal
excursion of the sagittal diameter is observed to correspond with
the epigastrium (Fig. 183), which can only result from the
inspiratory activity of the diaphragm. The fact, however, remains

Fie. 1S4. — Thoracic and abdominal pneumograms during waking (T and A) and sleep (T' A')-
(A. Mosso.) The curves are reversed, T and T' being traced with Marty's pneumograph, A A'
with Vierordt's sphygrnographic lever applied near the umbilicus.

that the function of the diaphragm is normally far less im-
portant than that of the external intercostals taken as a whole.
Hultkrantz has recently shown that in an individual who
takes in on an average 490 c.c. of air, 320 c.c. are to be referred
to thoracic dilatation, and only 170 c.c. to the depression of the
diaphragm.

Again, it appears from certain curves of thoracic and abdominal
respiration which Mosso recorded simultaneously in the waking
and the sleeping states, that the characteristic abdominal type of
human respiration in the waking state disappears in sleep, during
which the activity of the intercostals increases, while that of the
diaphragm is reduced to a minimum (Fig. 184).

As regards the question whether during normal quiet breathing
the external intercostals only corne into play by the raising of the
ribs, or whether the scaleni and levatores costarum breves et longi

xii MECHANICS OF KESPIKATION 419

are also involved, opinions are much divided, and no positive facts
can be adduced on either side.

On the other hand, it is clear that in forced respiration the
action of all these muscles is reinforced by that of other accessory
muscles, whose ordinary office is not to assist the dilatation of the
thorax. Such are the sterno-cleido-mastoid, the pectoralis major
and minor, the trapezius, serratus and extensors of the vertebral
column. Further, those muscles intervene actively which serve to
lower the larynx and widen the glottis, as well as the muscles of
the palate, fauces, and dilators of the nostrils.

Another question which is difficult to solve, and as to which
opinions are divided, is whether in normal quiet breathing expira-
tion takes place passively by simple elastic reaction, or is actively
promoted by the interosseous portion of the internal intercostals,
triangularis sterni, and serratus posticus inferior. The great
majority of writers, headed by Donders, adopt the first view ;
Fick's arguments in favour of the second seem to us, however, to
carry a certain weight. He showed that with a little practice,
active expiration can be performed voluntarily without throwing
the abdominal muscles into any kind of tension. This is easy by
concentrating the attention in expiration on dropping the upper
ribs and shoulders, and not breathing the air out forcibly, which
would throw the abdominal muscles into contraction. If during
this intentionally thoracic expiration a water manometer is
connected with the oral cavity, the meniscus can be seen to rise
4-5 cm., which gives a clear idea of the force exerted by the
thoracic muscles, and, according to Fick, proves the expiratory
action of the internal intercostals, as to which there has been so
much discussion. That these do take part even in normal
respiratory rhythm is shown by the fact that the expiratory act
can be voluntarily interrupted at any moment, which certainly
depends on voluntary inhibition of the expiratory muscles already
in action, and not upon the entry of the antagonistic inspiratory
muscles, about which we know very little.

Another cogent argument in favour of this theory seems to us
to lie in the tracings of normal human respiration, recorded by
Marey's pneumograph (Fig. 185). Neither the inspiratory nor
the expiratory excursions constantly reach the same abscissae, as
though drawn between two parallel lines ; but they are now
more, now less, extensive, according as in the different breathings
the contraction of the antagonistic muscles in individual respira-
tions was more or less intense.

To this it may be added that in dogs (Luciani, 1877) expiration
under normal conditions is always active, owing to the intervention
of the abdominal muscles, the contraction of which normally
prevails over the alternating contractions of the diaphragm,
in relation to intra-abdominal pressure, which, as we shall see,

420 PHYSIOLOGY CHAP.

rises during expiration and sinks during inspiration. This fact
increases the probability that in man also the normal expiratory
movements are active, even if this be due to participation of the
internal intercostals, and not of the abdominal muscles.

The most convincing evidence for the active character of
expiration under normal conditions also was, however, furnished
by Aducco (1887). From a series of ingenious experiments per-
formed on men and dogs, he adduced the following facts, which
show as a whole that in the expiratory process the contraction of
certain muscles co-operates with the elastic reaction of the lungs,
thorax, abdominal walls, and* intestinal gases : —

(a) Normal expiration, being favoured by many passive factors,
has in the waking state a longer duration than inspiration, which
meets with corresponding resistance from these same factors.

(6) Expiration proceeds quite regularly, even when some of its
principal passive factors are excluded, e.y. after the abdominal and

FIG. 18o. — Pneumograms taken with Marey's jkneumograph during normal, quiet breathing.
The lower abscissa is at the level of the dead point of the deepest inspirations ; the higher
abscissa at the dead point of the more active expirations.

thoracic cavities have been widely opened to exclude the elastic
reaction of the intestinal gases and distended lungs.

(c) When to the passive factors of expiration is added a force
which works in the same direction (a rubber sheath compressing
the thorax, a weight placed on the thorax), the time relations
between the two acts of respiration is very little altered.

(d} With artificial expiration on the dead body, when only
passive factors can come into play, a given weight is invariably
less displaced by the thoracic walls than in normal expiration.

(e) Given two expirations of equal strength, one made by the
living animal, the other artificially induced on a dead body of the
same, the positive tracheal pressure developed by the latter is
lower.

(/) If during sleep, thoracic and abdominal pneumograms are
taken on a person breathing through Miiller's water-valves, and
the pressure raised in the expiratory valve by adding a little water,
the curve (Fig. 186) shows that while thoracic expiration undergoes

xii MECHANICS OF RESPIRATION 421

little change in its course and duration, abdominal respiration
becomes slower in the middle of its period. This slowing is the
proof that in quiet breathing the abdominal muscles do not in any
way function as expiratory factors. On the other hand, the
absence of any effects of increased expiratory resistance in the
pneumograms of the thorax proves that the thoracic expiratory
muscles come actively into play, so that they readily overcome
this resistance. Thus, then, " thoracic expiration, even when
accomplished under conditions of perfect rest, as is the case in
sleep, is an active process."

VII. The respiratory movements, of which we have so far
treated, directly determine the alternate filling and emptying
with air of the lungs — inspiration and expiration. Besides these
respiratory movements in the strict sense of the word, there are
others, which affect the air-passages beyond the bronchial tubes and
the thorax, and indirectly favour pulmonary ventilation. These

FIG. 180. — Thoracic and abdominal pneumograms recorded (with two exploring button tam-
bours) during quiet sleep of an individual breathing with a mask through Miiller's water-
valve. (Aducco.) At T and A, the inspiratory and expiratory valves offer least resistance1.
At T' and A' the expiratory valve offers higher resistance owing to addition of a little water.
The effect of this greater resistance is seen in the descending expiratory line of the abdominal
tracing.

are known as accessory or concomitant respiratory movements.
Some of them are purely passive in character, i.e. they represent
simple secondary effects of the respiratory movements proper:
such are the movements of the larynx and trachea, which in
inspiration are drawn down by the expansion of the lungs and fall
of the diaphragm, rising again with the succeeding expiration.
Others, however, and it is these which must now be mentioned
briefly, are of an active character, due to the contraction of certain
special muscles.

In the first place, we must consider the respiratory movements
of the laryngeal muscles proper, which produce inspiratory dilata-
tion and expiratory constriction of the glottis. On some animals,
particularly dogs, these movements may be regularly observed,
while in men their presence in quiet breathing is much disputed,
since there seems rather to be a permanent widening of the glottis.
In a certain percentage of cases (16 per cent, according to Semon)
these movements are, however, perceptible in man during quiet
breathing.

422

PHYSIOLOGY

CHAP.

Next to the respiratory movements of the vocal cords come
those of the nostrils, which are essentially analogous with the
first, and also appear regularly in man, in a certain number of>
cases, while in some animals (e.g. rabbit) they are never wanting,,
and in others (e.g. the horse) they play a very important part,
paralysis of the corresponding muscles being apt to produce
suffocation. They consist in the expansion of the nostrils,
coincident with inspiration (or more accurately, commencing just
before the phase of inspiration proper), and a subsequent constric-

FIG. 1ST. — Apparatus for registering respiratory movements of an animal by the oscillations of
pressure in the respiratory passages. .S, Hutchinson's spirometer, to which is attached a
small metal pointer d which records the oscillations of pressure in the animal's trachea
upon the smoked drum ; R, large receiver from which the animal breathes, connected by
ft to spirometer, by h to the trachea. The tube c permits more or less rapid renewal of air
in receiver, according as the lumen is mere or less constricted.

tion, which coincides more or less exactly with the expiratory
phase.

In forced respiration (dyspnoea) these concomitant respiratory
movements occur, as we have seen, to an exaggerated degree, even
in individuals in whom they are not observed in normal quiet
respiration. Other movements are then associated with them, e.g.
foaming at the mouth, protrusion of the tongue, etc., etc., showing
that the object is to give free access of air to the respiratory
passages.

VIII. Ventilation or the renewal of the pulmonary air, effected
by the alternate movements of dilatation and contraction of the
thorax, varies in proportion to the varying intensity of these move-
ments. The name of tidal air is given to the volume of air which

xii MECHANICS OF KESPIRATION 423

enters and leaves the pulmonary air -passages during a normal
inspiration and expiration. It can be measured by a well-
calibrated and graduated glass bell, which Hutchinson (1860)
termed a spirometer (Fig. 187). A properly constructed gasometer,
which offers minimal resistance to the passage of the air, can
be substituted (Mosso).

The amount of tidal air varies, according to Yierordt, between
367 and 699 c.c. in an adult. The average generally taken
is. 500 c.c. With an average frequency of 16 respirations per
minute, the amplitude of pulmonary ventilation (Rosenthal's
respiratory capacity) amounts therefore to 8000 c.c. This
amount increases in proportion as the respirations are more
intense and deeper. Hutchinson gave the name of complementary
air to that amount which, after a normal respiration, may still be
breathed in by a maximal inspiration : of reserve air to that
which may be expelled after a normal expiration by a maximal
expiration ; and, lastly, he termed the sum of tidal, complement-
ary, and reserve air obtained on following a maximal inspira-
tion by a maximal expiration, the vital capacity. The values of
the determinations (by means of spirometers) of the volumes of
these different measures of air, vary considerably in experiments
undertaken on different individuals. According to Haeser's obser-
vations, the mean vital capacity of Germans is 3222 c.c. ; of English
(who are taller on an average;, 3772 c.c. The vital capacity is
affected not only by stature, but also 'by volume of trunk, body,
weight, age, sex, profession or trade, condition of digestion or
inanition, etc.

In order to avoid a gross error in spirometry, it is necessary, as v. Hoesslin
pointed out, to breathe into a receiver warmed to body temperature (by
heating the bottom or walls of the spirometer, or filling it with warm water).
Thus with a spirometer warmed to 37° C. the vital capacity amounted to
2850 c.c., while with the spirometer at 6° C. it was only 2375 c.c., a difference
of 16'5 per cent.

The air left in the lungs after a maximal expiration is termed
the residual air. It can be determined on the living by the
methods of H. Davy and Grehant, which consist, after making a
maximal expiration, in breathing for a certain time from a rubber
balloon containing a known quantity of hydrogen. When it is
supposed that all the residual air has mixed with the hydrogen,
the percentage analysis of the air in the balloon is taken, and the
value of the residual air is then found by an easy calculation.
In different experiments these observers found it to be 1230-
1640 c.c. On an average it can be assumed that the residual air is
equal to half the vital capacity (Gad).

It appears from the total of spirometric observations that in
each normal respiratory cycle or revolution only a portion of the

424 PHYSIOLOGY CHAP.

air in the lungs can be renewed, which part may be taken as
•corresponding to J-l.

If in the course of a series of normal quiet breathings a single
inspiration of hydrogen is made, and a sample of the air collected
from each succeeding expiration, to ascertain which no longer
contains any trace of hydrogen, the result is, approximately, that
after 6-8 cycles the whole air of the lungs is renewed; after
that time every trace of hydrogen in the expired air vanishes
(Grehant).

During the entrance of air into the lungs the pressure in the
air-passages becomes negative ; the pressure during the exit of air
from the lungs, on the contrary, is positive. In order to estimate
these variations of intrapulmonary pressure it is only necessary
to connect a mercury manometer with one nostril, while the
mouth is kept closed, and to breathe with the other nostril
(Bonders). It will be seen that in quiet breathing the mercury
column falls 1 mm. during inspiration and rises 2-3 mm. in
expiration. These oscillations are increased in forced respiration.

To ascertain the maximal values of negative and positive
intrapulmonary pressure, obtained by exerting all available in-
spiratory and expiratory forces, it is only necessary, starting from
zero pressure, to close the mouth and the open nostril, and then to
make the maximal inspiratory or expiratory effort. According to
Bonders, the maximal negative inspiratory pressure is on an
average = - 57 mm. Hg (36-74) and the maximal positive expira-
tory pressure = + 87 mm. Hg (82-100).

When we consider that on the one hand the iuspiratory
muscles have to overcome great resistances in order to dilate the
thorax and the extensible organs which it contains, and on the
other the expiratory muscles are assisted in their action by the
same conditions which hinder the action of the former, we must
(notwithstanding that the manometric value of the pulmonary
pressure indicates a greater effect of the expiratory than of the
inspiratory muscles) assume that the latter develop a distinctly
greater amount of energy than the former.

The oscillations of pressure along the respiratory tract may be used in
man as in other animals for recording tracings of respiratory movements.
The simplest method is to introduce one end of a tube into the nasal cavity
or the mouth, and to attach the other to a Marey's tambour. With
animals it is more convenient to insert a two- way cannula into the trachea,
one arm of which communicates freely with the external air, while the other
is connected by a rubber junction with the tambour. By constricting or
distending the lumen of the tube through which the animal breathes, a
greater or less fraction of the oscillations of pressure in the trachea! air can
be recorded on the registering apparatus.

A better and more exact method is that of making the animal breathe
into a very large vessel, communicating on the one hand with the trachea,
on the other with a writing tambour (Bert), or with a small and very
sensitive spirometer provided with a writing point that records the excursions

XII

MECHANICS OF RESPIRATION

425

on the rotating cylinder (Tigerstedt), as shown in Fig. 187. The chamber in
which the animal breathes must be entirely shut off when it is desired to
trace the progressive alterations in the respiratory movements due to
asphyxia (Luciani) ; otherwise it communicates with the outer air by a more
or less open tube, which allows the air within the bottle to be renewed when
required (Tigerstedt). In that case, however, the oscillations in the tracing
are not proportional with those of the intrapulmoiiary pressure.

The same effect may be obtained when the animal is breathing free
air, while, enclosed within a hermetically sealed glass cylinder (Knoll).
A tube tied in the trachea, or fitting closely over the mouth and nostrils
of. the animal, passes through one wall of the box and communicates with
the external air. The internal air of the box is connected by means of a
second tube with a recording tambour, and traces, like a plethysmograph,
the variations in the total volume of the animal, corresponding to the
iuspiratory and expiratory movements. The simplest application of this
method is that of Bernstein, represented in Fig. 188.

IX. Iii proportion as the negative in tra thoracic pressure
increases or diminishes in consequence of the inspiratory and
expiratory movements, the
lungs dilate and retract
with the air that pene-
trates through the glottis
to the pulmonary passages,
where equilibrium of air
pressure is restored.

Both in dilatation and
•in retraction of the lungs
the two layers of the
pleura, visceral and parie-
tal, remain, as we have said
in constant contact. At the
same time they glide one over the other, because the cavity of the
thorax, owing to the action of the respiratory muscles, does not
dilate and contract equally in all its diameters, but undergoes
perceptible changes of form, particularly at the base, so that the
lungs (which must passively follow the excursions of the thorax)
also change their form in order to adapt themselves to the new
shape of the thoracic cavity (Bonders).

The most immovable part of the lungs, which undergo the
least displacement, are the roots, the apices, the posterior border,
and that portion of their external surface which underlies the
lateral parts of the vertebral column ; the most mobile are those
farthest removed from the tixed parts, i.e. their inferior and
anterior borders, and the median surfaces. The movement of the
pleural layers, therefore, takes place specially in the longitudinal
direction from above downwards, and in the transverse direction
from behind forwards.

Under normal conditions this movement can be distinguished
by percussion, which yields a clear, full sound in every part of the

Fm. 188.— Bernstein's pneumoplethysmograph or spiro-
graph. Hermetically sealed glass cylinder, in which
the animal breathes the external air freely from the
mask c and tube a. The rubber tube b, communicating
with the inside of the cylinder, is connected withta
Marey's tambour and writing-lever.

426

PHYSIOLOGY

CHAP.

thoracic wall beneath which there is pulmonary substance, and a
dull sound where there are viscera which contain no air. The
lower border extends in normal expiration from the sternal margin,
on both sides almost to the insertion of the sixth rib, in the
axillary line almost to the upper border of the seventh (Fig. 189).
The anterior margin of the left lung, in ordinary expiration,
reaches the line that goes from the median point of the insertion
of the fourth rib to the insertion of the sixth (see line ft").

In deep inspiration the inferior borders of the lungs pass
beyond the sixth and reach the seventh rib (see line mri), posteriorly
they reach the eleventh ; the anterior margin of the left lung
comes forward to the line ii'.

FIG. 189. — Displacement of pulmonary borders in respiratory movements. (Landois.) The line atb
indicates the lower border of the lungs when all the respiratory muscles are at rest. The line
mn indicates the right pulmonary border in deep inspiration ; hi in deep expiration. The
triangle tt't" corresponds with area of absolute dulness of heart when thorax is at rest.
In deep inspirations this area is reduced to the small triangle fit' owing to advance of internal
border of left lung ; in deep expiration, on the contrary, the triangle extends to tee' by the
retraction of this border. The line dd'd" limits the area of relative dulness of heart, the heart
being separated from the thoracic wall by a thin sheet of lung.

In very energetic expiration the lower borders of the lungs
rise to the line hi ; the anterior margin of the left lung protrudes
as far as the line ee'.

In phuritis exudativa, when the pleural layers become
roughened on the surface, their friction during the respiratory
movements gives rise to a characteristic murmur of friction, which
the physician uses in diagnosis.

With direct auscultation, and with the stethoscope, a
murmur is heard on inspiration throughout the whole extent of
the lungs, which is known as the vesicular murmur, because it de-
pends on the dilatations of the alveoli and the friction of the air
that traverses the bronchioles. The murmur is rougher in children
up to the age of twelve, because the pulmonary infundibuli are

xii MECHANICS OF RESPIRATION 427

about J smaller than in adults. In expiration a weak and c^uiet
murmur is heard.

In auscultating along the larger respiratory passages (larynx,
trachea, great bronchi), both in inspiration and in expiration a
harsh murmur is heard, sharp and clear, resembling the guttural
German cli, which is known as the bronchial murmur. This is
perceptible not merely in the neck, along the larynx and trachea,
but also in the thorax between the two shoulder-blades at the
le.vel of the fourth dorsal vertebra, the point at which the bronchi
bifurcate. It is a little more accentuated on the right side,
because the right bronchus is of greater calibre and is stronger as
a rule in expiration than in inspiration. In the other parts of the
thorax the bronchial murmur is imperceptible, being covered by
the vesicular murmur. But it is heard distinctly in certain parts
of the pulmonary area, when the alveoli are atelectatic or
infiltrated. In pneumonia, accordingly, the area of lung that
has become impervious to air, or hepatised, (-an be determined

FIG. li»0. — Respiratory oscillations of intruthoracic pressure (T) ami intra-abdominal pressure (A
in anaesthetised cloy;. (Luciaiii.)

from the extent of the region in which the bronchial murmur
is abnormally audible.

X. As above stated it is not only the lungs, but also the heart
and blood-vessels that feel the effects of the changes in pressure
determined by respiratory rhythm.

To obtain an exact knowledge of these effects it is necessary
first to study the oscillations of intrathoracic and intra-abdominal
pressure in the two periods of the respiratory cycle or revolution.
This is most simply effected by the method of the oesophageal or
rectal sound, in conjunction with Marey's recording tambour
(Luciani, 1878 ; Rosenthal, 1880).

The tracings of Fig. 190, which we obtained by this method
from an anaesthetised dog, are highly instructive, since they show
that the respiratory oscillations of pressure within the thorax and
abdomen are not coincident but interfering. While intrathoracic
pressure falls during inspiration and rises in expiration, i intra-
abdominal pressure rises in the first period of inspiration and
falls in the second, and falls in the first period of expiration and

428 PHYSIOLOGY CHAP.

rises again in the second. To interpret these facts it is necessary
to assume that the diaphragm intervenes actively only in the first
period of inspiration, and that the abdominal muscles intervene
actively only in the second period of expiration. This agrees with
what was stated above as to the relative inspiratory importance
of the external intercostal muscles, and the constantly active
character of the expiratory movements.

The respiratory oscillations of pressure in the two great
body cavities are the more ample, or extensive, in proportion as
the entrance and exit of air from the pulmonary passages, which
tends to compensate them and to re-establish equilibrium, is more
difficult. This fact can be experimentally verified by recording
the tracings of intra-abdoniinal pressure in a tracheotomised animal,
and observing how the respiratory curves are modified when the
lumen of the tube attached to the tracheal cannula is constricted.
Fig. 191 shows that the effect consists more particularly in a con-
spicuous exaggeration of the inspiratory acts, which become deeper

FIG. 191. — Respiratory oscillations of intratliuracR- pressure (T) and intra-alxlominal pressure (A)
in anaesthetised and traclieotomised dog. At B the tracheal tube was constricted. (Lnciani.)

and longer. Expiratory activity is also exaggerated, but in a less
degree, and with reference solely to intensity and not to duration.
The interference of the two curves, intrathoracic and intra-
abdomlnal, persists.

The determination in the different higher animals, and in man,
of the absolute values of the respiratory oscillations of intra-
thoracic and intra-abdominal pressure has not been fully worked
out. We have only the few data obtained on the rabbit from
Adamkiewicz and Jacobson, and those of Kosenthal, which show
that in this animal, in normal inspiration, the pressure falls
to - 40 mm. water ( = - 3 mm. Hg), and that in the most intense
inspirations, with closed trachea, the negative pressure may amount
to - 250 mm. water ( = - 20 mm. Hg).

More recently certain observers (Ewald, Einthoven, Aron, van
der Brugh) have succeeded by means of a special apparatus (with-
out causing pneumothorax) in introducing into the pleural cavity
a cannula attached to a manometer, and thus directly measuring
the pressure of the pleural cavity. Einthoven and his pupil,
van der Brugh, found during expiration a negative pleural

XII

MECHANICS OF RESPIRATION

429

FIG. 19± — Luciuni's oesophageal explorer. Elastic
sound, covered at the end with tint- rubber

pressure equal to - 80, during inspiration equal to - 102 mm.
of water.

The simplest method for recording the oscillations of intrathoracic preSvSiire
in animals is to introduce into the oesophagus, after previous oesophagotorny,
an elastic sound, or hollow metal tul>e, covered at one end with a fine rubber
membrane, which is connected with a writing tambour, after ligation of the
oesophagus (Fig. 192). This last operation is necessary to ensure the perfect
occlusion of the oesophagus above the exploring sound, Avhile beneath it the
tonicity of the cardiac orifice is
sufficient to guarantee closure, save
at the moment of deglutition, which
rarely occurs in the narcotised
animal. The imperfect closure of
the oesophagus, after introducing sheath.
the sound by the mouth or nostril,

makes it difficult to obtain these oscillations of intrathoracic pressure in
man (Rosenthal). It might be possible to remove this inconvenience by
the expedient employed bv PM^er and Ludwig in their pulmonary catheter
(Fig. 170, p. 388).

Bert's method may be, employed for recording the iiitra-abdomiiial pressures.
This consists in the introduction into the rectum of a glass tube, fixed against
the anal sphincters by a kind of pessary to make it air-tight, and connected
with a water manometer and writing tambour (Fig. 193, A). The inter-
vention of a manometer is, however, superfluous,
and no special contrivance is required to ensure
closure of the anal orifice, which was sufficiently
guaranteed by the tonic contraction of the.
sphincters. The same object can be effected by
the introduction of a short length of urethra!
catheter of large diameter, perforated in several
places,; and provided at the ends and centre
with three circular ridges formed of rubber
rings, over which is drawn a thin membrane
(Luciani). This method is applicable toyman,
and is invariably successful, so long as the

F*o. 193.— Rectal explorers— Bert (A) precaution is taken of emptying the intestine
and Luciani (B). A, Glass tube, of t],e faeces accumulated at the lower end
open at the end, which is in- .-„. -.„„ ^
troduced into the rectum and (.rig. *•«*«*} &)•
plugged in anal aperture by in-
flation of a hollow elastic pessary -^r r -\\J-t ,1 t 1 A 1

joined to the tube. B, Elastic or XL Whatever the absolute values

metal sound, with two lateral nf fkpcp nspillnfinrisj nf r»re»aanra in the*

openings, fitted with three rubber ( tnese osciiiauoiis oi pressure in tne
Covered with a small fine two body cavities determined by re-
spiratory rhythm, it is evident that they
must have a considerable influence on the centripetal course of
the blood in the veins, and be an effective aid to the circulation
as controlled by the heart.

This physiological doctrine is fairly ancient. Valsalva (1760)
and Haller (1766) seem to have been the first who observed on
man the swelling and emptying of the jugular vein coincident
with expiration and inspiration. David Barry (1825), from the
aspiration of coloured fluid along a tube fastened centrally in the
jugular, formed an exaggerated notion of the functional importance
of inspiratory thoracic aspiration. Wedenieyer (1828) repeated

430 PHYSIOLOGY CHAP.

the same experiments with more discretion. Poiseuille (1831)
applied his haemodynamouieter to the veins, and attempted to
reduce to figures the force of the aspiration exerted in the/
inspiratory act, and to establish at what distance from the thorax
its influence ceases. With the discovery of Ludwig's Kymograph
(1847) began the series of researches by the graphic method, which
were directed to the more exact determination of the influence
of respiratory mechanics upon blood pressure in the veins and
arteries (see p. 242).

In Fig. 194 we have a very clear representation of the intra-
thoracic respiratory curves and the simultaneous curves of blood
pressure in the vena cava superior. Apart from the secondary
oscillations which depend on cardiac rhythm (see Chap. VII. 10),
it will be seen that the respiratory curves follow the same course,
and coincide with them, apart from a slight delay which the curve
of venous pressure exhibits in relation to that of intrathoracic

FIG. 194. — Respiratory oscillations of intrathoracic pressure (T) and pressure in vena cava superior
(C) in anaesthetised and tracheotomised dog. (Luciani.) T, taken with oesophageal explorer ;
C, with water manometer — both connected, to Marey's recording tambours.

pressure, which is probably dependent upon the presence of the
water manometer. It may therefore be concluded that the negative
pressure of the intrathoracic wave suffers diminution during the
inspiratory act, so that the velocity with which the blood flows
from the extrathoracic into the intrathoracic vein and the heart,
increases proportionately. The opposite occurs during the ex-
piratory act.

When the effects of the respiratory movements are exaggerated
by constriction of the lumen of the tracheal tube, the respiratory
curves become more extensive, whether they are transmitted
from the oesophageal sound or from the vena cava superior (Fig.
195).

The impulse given to the venous circulation by the inspiratory
movement is not counterbalanced by the opposite effect of the
•expiratory movement. Expirations are, in fact, always somewhat
slower than inspirations; further, intrathoracic pressure always
remains negative even during the ordinary expiratory acts, so that

XII

MECHANICS OF EESPIEATION

431

it invariably favours the centripetal course of the blood in the
veins : lastly, the effects of the respiratory undulations of intra-
abdominal pressure must also be taken into consideration. They
are always favourable to the course of the venous blood, especially
when the expirations are assisted by the active intervention of
the abdominal muscles, as, according to our experiences, occurs
constantly in the dog.

FIG. 195.— Continuation of last figure. At B the tube connected with the trachea was slightly

constricted.

Fig. 196 is highly instructive, because it shows that the
respiratory undulations of pressure in the vena cava inferior are
approximately coincident with, and present the same course as,
those simultaneously traced by the superior vena cava. This

Cs

FIG. 190 — Respiratory oscillations of pressure in vena cava superior (Cs) and vena cava inferior
(Ci) in chloroformed dog. (Luciani.) In Ci the descending inspiratory line exhibits a pause,
due to action of diaphragm, which is not seen in Cs.

proves the active intervention of the abdominal muscles, which
during expiration produce a pressor effect upon the inferior vena
cava, while the action of the diaphragm during inspiration is only
capable of reducing the depressor effect due to the relaxation of
the abdominal muscles.

XII. The influence exerted by the respiratory movements
upon the pressure and centrifugal course of the blood in the
arteries must necessarily be the opposite of that which it exerts

432 PHYSIOLOGY CHAP.

upon the veins. It should, however, be remembered that the
arteries are not subject in the same degree as the veins to the
effects of the oscillations of intrathoracic and intra - abdominal
pressure. The walls of the arteries are in fact more robust, less
yielding, and are under high pressure. They are more liable to
the effects of the functional modifications of the heart induced by
the respiratory movements than to the direct consequence of these
movements.

Generally speaking, physiologists in investigating the re-
spiratory waves of arterial blood - pressure have arrived at
sufficiently disparate results. This appears to us to be due less to
fallacies in the observations or to the method employed, than to
the varying effects of the respiratory mechanism upon arterial
pressure, according to the form and intensity of respiratory
rhythm. This may be extremely frequent and superficial, or
extremely infrequent and deep ; and between these two extremes

Fio. 107. — Respiratory oscillations of intrathoraeic pressure (T) and pressure in carotid artery
(A) in a chloroformed dog. (Luciani.) Tracing A was taken with a Chauvean and Marey's
sphygmoscope.

many gradations of form may be observed, between which the
normal type represents the centre of the scale.

With extreme frequency of respiration, arterial pressure does
not undergo any sensible modification, because the effects of
inspiration are obliterated by those of expiration, which rapidly
succeed them. But when the respiratory rhythm is not exces-
sively frequent, and is very intense, the respiratory undulations
do appear on the tracings of arterial pressure, and may suffer the
same delay, and coincide approximately with the waves of
intrathoracic pressure. This is apparent in the tracings of
Fig. 197, registered on a chloroformed dog, which in ten seconds
gave nine profound respirations and thirty-nine cardiac beats.
It will be seen that arterial pressure rises at each expiration, and
falls with each inspiration. It is highly probable that these
results depend essentially upon exaggerated expiratory activity of
the abdominal muscles, which obstructs the arterial blood-stream
flowing to the abdomen by compression of the capillaries, thus
producing indirect rise of pressure in the intrathoracic arteries,

XII

MECHANICS OF KESPIKATION

similar to that which constantly occurs when the abdominal wall
is compressed by the hand along the course of the aorta.

When the respiratory rhythm begins to assume its normal
form, in respect of frequency and intensity, its influence on
arterial blood pressure diminishes proportionally till it entirely or
almost disappears, as seen in the tracings of Fig. 198. A similar
result was obtained by Marey, who explained it by the antagonistic
influence exerted by the movements of the diaphragm on the

FIG. 198. — Respiratory oscillations of pressure in vena cava superior (Cs) compared with tracing
of pressure in carotid artery (Ac) in chloroformed dog. (Luciani.)

pressure of the thoracic and abdominal cavities. This interpreta-
tion does not seem to us correct, when we consider on the one
hand the secondary part played by the diaphragm in respiratory
mechanics, and on the other the strong and constant expiratory
activity of the abdominal muscles as observed in the dog. It
suffices, in order to explain the small or negative effect of ordinary
respiratory rhythm on arterial pressure/ to admit that normally

FIG. 199. — Tracing of intrathoracic pressure (To) and carotid (Cd) in non-anaesthetised dog of
medium size, showing slight trembling, particularly in expiration. (Luciani.)

the respiratory movements are accomplished slowly and quite
gradually, and that the abdominal muscles either act moderately
during expiration (dog), or remain completely inactive (man).

When the respiratory rhythm becomes very slow and deep,
a marked interference is perceived between the respiratory waves
of intrathoracic pressure and the respiratory curves of arterial
pressure. This phenomenon was first illustrated by Einbrodt
(1860) in an excellent publication from Ludwig's laboratory.
The tracings of Fig. 199 show the phenomenon in the most

VOL. i 2 F

434 PHYSIOLOGY CHAP.

classical form in which it has ever been recorded. At the first
moment of expiration the arterial pressure rises, falling in the
second period ; in the first period of inspiration it continues tp
fall, and then rises at the second. Arterial pressure therefore
reaches its maximum in the first period of expiration, and its
minimum in the first period of inspiration.

In explanation of this fact Einbrodt assumes that the
inspiratory fall of intrathoracic pressure, by determining an
acceleration of the venous current, favours the diastolic refilling of
the heart, which is followed by a larger systolic outflow, raising
arterial pressure. This increase is maximal during the first
period of expiration, either on account of the previous excess
filling of the heart, or from the expiratory increase of intrathoracic
pressure, which favours the centrifugal course in the arteries and
the systolic action of the heart. In the second period of expira-
tion the arterial pressure falls owing to retardation of the venous
current in the blood, which diminishes the diastolic refilling and
systolic emptying of the heart.

This theory is inadequate, because it takes no' account of
the pressor influence of the abdominal muscles, which is capable
of raising arterial pressure during expiration, by compressing
the capillaries of the vessels belonging to the intra-abdominal
aortic system.

Funcke and Latschemberger (1877) held the fundamental
cause of the phenomenon to lie in the changes of capacity in the
capillary pulmonary system, effected by the alternate dilatation
and retraction of the lungs, the respiratory oscillations of pressure
in the thoracic cavity being only of secondary importance. They
found in fact -that in curarised rabbits, during artificial respirations
by the bellows, with open thorax, there were still respiratory
oscillations of carotid pressure. They explained this fact by
admitting that when the alveoli of the lung dilate (whether from
positive tracheal, or from negative pleural pressure) the capillary
network which they contain must become stretched, with a
consequent elongation and constriction of the vascular lumen,
resulting in a considerable diminution in their capacity. The
opposite changes must occur at each expiratory retraction of the
pulmonary alveoli, which increases the capacity of the capillary rete.
Given these effects of the respiratory movements, they must not
merely influence the course of the blood in the lesser circulation,
but. must also act indirectly upon the pressure of the aortic
system, which is fed from the pulmonary blood. The inspiratory
increase in pressure would depend upon the expulsion of the
blood from the compressed pulmonary capillary system into the
left heart; the expiratory fall of pressure, on the retention of the
blood in the newly dilated capillaries of the lungs.

This theory, if not wholly unfounded, is at any rate very

xii MECHANICS OF KESPIRATION 435

exaggerated. The respiratory oscillations of arterial pressure
are not obtained with open thorax, unless the rhythmical
pulmonary dilatation with the bellows is grossly exaggerated.
The same authors constantly observed that the respiratory waves
of arterial pressure obtained with closed thorax in the curarised
rabbit, with a medium degree of rhythmical insufflation, became
notably weaker, or even disappeared altogether, when the pleural
cavity was scarcely yet open, and it was only on increasing the
insufflations that they could be made to reappear, or resume their
former level.

This fact shows the predominating importance of the oscilla-
tions of intrathoracic and intra-abdominal pressure, as causal
factors in the respiratory arterial undulations.

Heinricius and Kronecker (1888), taking up Einbrodt's experi-
ments, showed that whatever impeded the cardiac diastole lowered

FIG. 200. — Tracings of intrathoracic pressure (To), pressure in crural artery (Acr\ and in carotid
artery (Acn) in anaesthetised dog with cut phrenics. (Luciani.)

arterial pressure, and whatever facilitated and aided the former
increased the latter. The influence of the respiratory movements
of the filling and emptying of the heart would thus be the funda-
mental condition of the respiratory waves of arterial pressure.
" Regular respiration," according to these authors, " produces a
salutary massage of the heart."

In order adequately to interpret the arterial respiratory wave,
the influence which respiratory rhythm, when sufficiently pro-
nounced, can exert on cardiac rhythm must also be taken into
account. When the vagi are highly excitable, cardiac accelera-
tion may frequently be observed in inspiration, and a delay in
expiration. The tracings in Fig. 200 give a striking example <ff
this phenomenon. Since this effect disappears after section of
the vagi, Einbrodt correctly takes it to be the effect of a reflex
rhythmical excitation of the bulbar centre of the cardiac vagi
during the expiratory acts.

436 PHYSIOLOGY CHAP.

XIII. It is easy from the above to deduce the beneficial influ-
ence of the respiratory mechanism upon the circulation of the blood
(and lymph), as shown more particularly in the aspiration exerted
by the thorax during inspiration, which accelerates the centripetal
current, and increases the filling of the heart. This inspiratory
influence cannot be eliminated by the contrary effects of the
expiratory movements, particularly when the abdominal muscles
intervene actively, as has constantly been verified on certain
animals.

Some observers, however, particularly Filippo Pacini in Italy,
have exaggerated the importance of the respiratory mechanism on
the circulation of the blood, contending that a drowned person
whose cardiac movements have practically ceased, can be brought
back to life merely by artificial respiration. The untenability of
this view is shown by two classical experiments, one devised by
Valsalva (1740), the other by Johannes Miiller (1838), which
consist in determining what influence can be exerted by the
respiratory movements on the circulation, under conditions in
which the respiratory oscillations of intrathoracic and intra-
abdominal pressure are in a position to exert maximal influence
upon the course of the blood, or more accurately upon the entrance
and exit of the blood from the thoracic cavity.

If the glottis is closed after a deep inspiration, and a strenuous
and prolonged expiratory effort is then made, such pressure can be
exerted on the heart and intrathoracic vessels that the movements
and flow of the blood are temporarily arrested (Valsalva). Pro-
nounced swelling of the veins, visible principally in those of the
neck and face, evacuation of the vessels in the pulmonary system,
and surcharge of the systemic circulation, cessation of cardiac
sounds, and disappearance of the arterial pulse, can all be witnessed
(E. H. Weber, Bonders).

If instead of a forced expiration, the glottis is closed, and a
prolonged inspiratory movement made, the heart and all the intra-
thoracic vessels fill to such an extent that the arterial pulsations
cease, owing to the surcharge of the lesser, and comparative
evacuation of the greater circulation (J. Miiller).

These experiments cannot be performed without a certain
amount of risk, particularly to individuals who are no longer
young, and whose cardio- vascular system is no longer vigorous and
functioning normally. They may, however, be conveniently re-
produced on an artificial schema which represents the thoracic
cavity, lungs, heart, and related vessels, as shown in Fig. 201.

The results of these researches show that the respiratory
movements are only favourable to the circulation of the blood
when they are performed quietly, in a normal manner and with open
glottis, so as not to disturb cardiac activity, or compress or dilate
the heart to any extent. It is then seen (as can readily be con-

XII

MECHANICS OF KESPIEATION

437

firmed on the schema) that the inspiratory movements assist the
venous (and lymphatic) current, and favour the diastolic filling of
the heart, while the expiratory movements facilitate the arterial
current and systolic evacuation of the heart.

XIV. The rhythmical respiratory movements suffer various
modifications, in abnormal or unusual conditions, or to satisfy
various temporary needs or occurrences, or, lastly, as the motor
expression of special sentiments of pleasure or pain, fatigue, ennui,

FIG. 201.— Schema to demonstrate effect of strong positive and negative intrathoracic pressures
upon heart and blood-stream. (Landois.) D, U', stout elastic membrane which closes the
floor of a bell-jar, and can be pushed up or down by a handle, to imitate expiration and
inspiration. P, P, and P' P', two thin rubber balloons, to imitate the lungs, communicating
with a central tube, representing the trachea, which passes through the centre of the bell-
glass, with tap r to simulate the glottis. CC', a rubber ball, to represent the heart, com-
municating on one side with the tube V, V, which represents the afferent vessels of the heart
(provided with a valve that opens in inspiration and closes in expiration), on the other with
the tube A, A', representing the efferent artery, (with valve that, closes in inspiration and
opens in expiration). When r is closed, the manometer M shows a marked diminution of
pressure, with dilatation of heart and lungs, in inspiration ; in expiration it shows marked
increase of pressure, while the heart and lungs retract.

sleep, etc. The principal forms may be briefly summarised as an
appendix to the mechanics of respiration.

When there are mechanical impediments to the thoracic or
abdominal respiratory movements, e.g. plaster bandages applied to
the chest or epigastrium, the activity of the diaphragm or the
levator muscles to the ribs, respectively, is exaggerated, and the
rhythm becomes deeper and slower.

When the respiratory movements cause or increase pains in
the thorax or abdomen, respiratory rhythm becomes more frequent
and superficial.

Where there is morbid stenosis of the air-passages, the respira-
tions become deeper and less frequent. In pneumonia or pleurisy,

438 PHYSIOLOGY CHAP.

with effusions into the pleural cavity, both frequency and depth
of rhythm are accentuated.

Both secretions and exudations along the air-passages, as also
foreign bodies, solid, liquid, or gaseous, which penetrate them,
readily produce a reflex cough. This consists in loud, expiratory
efforts, which produce enforced opening of the previously closed
glottis, and by means of which the irritant is expelled. Coughing
may be voluntary, and even when the cough is involuntary, it can
be moderated and even inhibited by the will.

The presence of mucus, of foreign bodies, or of substances which
irritate the nasal mucosa, may give rise to sneezing, which consists
in one or more sudden and noisy expirations through the nasal
passages, preceded by profound inspirations. In sneezing, the
glottis is always open, the posterior nares are constricted by the
rise of the soft palate, the mouth is seldom open. It is invariably
a reflex act, which can only be imitated imperfectly by the will ;
it can, however, be voluntarily modified. The use of snuff makes
the nasal mucosa insensitive after a few days, and suppresses
sneezing.

Noisy crying, such as is frequent in childhood and youth, as
the expression of physical and moral pain, consists in short and
spasmodic inspirations, followed by prolonged expirations, with
constricted glottis, relaxed muscles of face and jaw, simultaneous
flow of tears and emission of high, inarticulate, laryngeal sounds.
Sometimes it is associated with sobbing, which consists in repeated
contractions of the diaphragm, producing sudden closure of the
vocal cords, with a characteristic and quite involuntary sound.

Noisy laughter, the expression of sudden pleasant and un-
expected sensations, or of hysteria, consists in short and rapidly
succeeding expiratory efforts through the vocal cords, which are
now brought close, and now separated, producing high, clear, and
inarticulate tones, with trembling of the soft palate. The mouth
is generally open, and the facial muscles contract in a characteristic
manner. Laughter can easily be imitated at will, and to a certain
extent can be voluntarily suppressed or moderated.

Yawning, the external expression of ennui, drowsiness, hunger,
consists in a long, deep inspiration, in which many of the accessory
inspiratory muscles participate, while the mouth, fauces, and
glottis open convulsively. Inspiration is followed by a shorter
expiration, and the two acts are accompanied by prolonged
characteristic sounds, and by a general stretching of the arms and
trunk. It is always an involuntary modification of breathing,
easily imitated by the will.

xii MECHANICS OF EESPIEATION 439

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MARTIN und HARTWELL. Journ. of Physiol., ii., 1879.

ROSENTHAL. Handbuch d. Physiol. von Hermann, iv. 1882.

BERNSTEIN. Arch. f. d. ges. Physiol. xxviii., 1882, xxxiv., 1884.

HERMANN. Arch. f. d. ges. Physiol. xxx., 1882, xxxv., 1884.

A. FICK. Festschrift des Vereins f. Naturkunde zu Cassel, 1886.

V. ADUCCO. Atti della R. Accademia delle scienze di Torino, xxii., 1887.

G. HEINRICIUS und H. KRONECKER. XIV. Abhandl. d. math. phys. Klasse der
Konigs. Sach. Gesellsch. d. Wissensch., 1888. (At the end of this monograph
there is a list of the publications down to 1888 "iiber den Einfluss der
Respirationsbewegungen auf den Blutlauf im Aortensystem.")

R. FICK. tJber die Ateinnmskeln. Arch. f. Anat., 1897, Supp. vol.

R. DU BOIS-REYMOND. Mechanik der Atmung. Ergebnisse der Physiol., I.
Jahrg., 2 Abt., 1902 (review of the subject).'

Recent English Literature : —

F. H. BARTLETT. On the Variations of Blood Pressure during the Breathing of

Rarefied Air. Amer. Journ. of Physiol., 1904, x. 149-163.
M. P. FITZGERALD and J. S. HALDANE. The Normal Alveolar Carbonic Acid

Pressure in Man. Journ. of Physiol., 1905, xxxii. 486-494.
C. C. GUTHRIE and F. H. PIKE. The Effect of Changes in Blood-Pressure on

Respiratory Movements. Amer. Journ. of Physiol., 1906, xvi. 475-482.
C. C. GUTHRIE and F. H. PIKE. Further Observations on the Relation between

Blood Pressure and Respiratory Movements. Amer. Journ. of Physiol., 1907-

1908, xx. 451-456.
J. F. HALLS DALLY. A Contribution to the Study of the Mechanism of Respiration,

with especial reference to the Action of the Vertebral Column and Diaphragm.

Proc. Roy. Soc., 1908, Lxxx. B. 182-187.
L. HILL and M. FLACK. The Effect of Excess of Carbon Dioxide and of Want of

Oxygen upon the Respiration and the Circulation. Journ. of Physiol., 1908,

xxxvii. 77-111.
A. E. BOYCOTT and J. S. HALDANE. The Effects of Low Atmospheric Pressures

on Respiration. Journ. of Physiol., 1908, xxxvii. 355-377.
R. 0. WARD. Alveolar Air on Monte Rosa. Journ. of Physiol., 1908, xxxvii.

378-389.

J. S. HALDANE and E. P. POULTON. The Effects of Want of Oxygen on Respira-
tion. Journ. of Physiol., 1908, xxxvii. 390-407.

CHAPTEK XIII

THE NERVOUS CONTROL OF RESPIRATORY RHYTHM

CONTENTS. — 1. Motor nerves to respiratory muscles and smooth muscle cells of
bronchi. 2. Bulbar respiratory centres and their localisation. 3. Spinal respira-
tory centres. 4. Cerebral respiratory centres. 5. Each of these centres results
from the association of an inspiratory and an expiratory centre, which function
rhythmically and alternately. 6. Automatic regulation of normal respiratory
rhythm, by afferent pulmonary fibres of vagus. 7. Influence exerted on respiratory
rhythm via the cerebral tracts and sensory nerves in general. 8. Phenomena
consequent on the separation of the bulb from the brain and spinal cord. 9.
Dyspnoea and its different forms. 10. Eupnoea or normal quiet respiration. 11.
Experimental apnoea from artificial respiration with the bellows. 12. Foetal apnoea,
and the analogous forms of experimental apnoea that can be produced in the adult.
13. Voluntary, as compared with experimental apnoea. 14. Apnoea produced
by continuous ventilation in birds. 15. Periodic respiration, or Cheyne-Stokes
phenomenon. 16. Physiological theory of respiratory rhythm. Bibliography.

THE previous chapter shows that the respiratory processes are
highly complex, owing to the number of muscles, anatomically
very distinct, and even remote from each other, which co-operate
in them. Their efficacy in determining the rhythmical dilatation
and constriction of the thoracic cavity, and consequent pulmonary
ventilation, which are indispensable to life, is entirely due to co-
ordination, i.e. to the harmonious association and sequence of the
contractions of the individual inspiratory and expiratory muscles.
If, for example, the external intercostals were to contract before
the scaleni, or if the diaphragm became active along with the
internal intercostals, no adequate renewal of pulmonary air would
. be obtained except with a useless expenditure of energy.

Since the rhythmical activity of respiration results from the
co-ordinated functions of many and very distinct muscles, it cannot
be founded (as that of the heart may possibly be), on a physio-
logical property inherent in the muscles, but must necessarily
depend (as the facts prove clearly) upon the rhythmical co-
ordinating function of complex nervous processes, which are the
subject of the present chapter.

I. the nervous mechanisms on which the respiratory rhythm
depends are as follows : —

(a) Motor nerves to the individual muscles which take part in
the inspiratory or expiratory movements ;

440

CHAP, xiii KESPIKATOKY KHYTHM 441

(&) A central organ, or, better, a complex of nerve centres,
interassociated, and constituting a small system ;

(c) Afferent nerves capable of modifying, directly or indirectly,
the activity of the said centres.

The motor nerves to the muscles, which normally determine
inspiratory expansion and expiratory retraction of the thorax, all
arise in the anterior roots of the spinal nerves. The motor nerves
to the scaleni emerge from the cervical tract, more exactly from
the second to the seventh nerves, and thus form the cervical and
brachial plexus, from which the branches to the muscles are given
off. The phrenic nerves which serve the diaphragm take origin
specially in the fourth cervicals, but are reinforced by fibres from
the third and also from the fifth pairs. The levatores costarum
longi et breves, the external and internal intercostals, and the
abdominal muscles receive nerves from the thoracic pairs of the
spinal cord : and, in particular, the rami posteriores of the dorsal
nerves serve the levatores costarum ; the intercostal nerves, the
muscles of the same name ; and the internal or anterior branches
of the intercostals, the muscles of the abdomen, which also receive
fibres derived from the first lumbar pair.

Physiological proof of these morphological data is afforded by
the following experiments. A transverse section through the
spinal cord below the exit of the last intercostal nerve leaves all
respiratory movements entirely unaffected, while a cross-section
in the thoracic cord paralyses all the respiratory muscles, the
nerves of which arise below the section. When the lower part of
the cervical cord is transversely divided, i.e. above the first inter-
costal and below the exit of the fifth cervical nerves, all the
motor muscles of the ribs are paralysed (with the partial excep-
tion of the first two, which are raised by the scaleni^ so that the
respiratory movements are effected almost exclusively by the
rhythmical activity of the diaphragm (Fig. 86, p. 229). If the
results of this operation are compared with those following the
section of the phrenic nerves (Fig. 202), they show the extreme
functional importance of the intercostal as compared with the
diaphragmatic muscles — paralysis of the latter being in no way
dangerous to the life of the animal, save in the case of young
rabbits, in which the thorax is not sufficiently rigid, nor the
thoracic muscles sufficiently developed, to allow of ready compen-
sation for the failure of the diaphragm. These observations are
confirmed by those made on the human subject, which show that
after paralysis of the diaphragm the respirations become somewhat
more frequent, but are accomplished solely by the muscles to
the ribs with no active co-operation of accessory muscles.

When the section through the cord is made above the exit
of the third cervical nerves, as far as the apex of the calamus
scrip torius, all the respiratory muscles properly so-called are

To

442 PHYSIOLOGY CHAP.

paralysed, including those of the diaphragm, and only the
rhythmical movements of the glottis and the muscles of the lips
and nose persist, which, as we have seen, not infrequently accom-^
pany the rhythmical movements of the thorax. These muscles
are served by nerves, which emerge from the medulla oblongata ;
the muscles of the lips and nose receive branches from the facial
nerve, and the muscles of the larynx are innervated by branches
of the vagus (the crico-thyroid muscle from the superior laryngeal,
and the rest of the laryngeal muscles from the inferior laryngealjf
The vagus also provides the motor nerves to the smootn
muscles of the bronchial tubes. This""was lirst demonstrated by\
LSnget"(i^42); it was subsequently contested, and finally confirmed
by the later experiments of Bert, Schiff, Gerlach and others. The
fact that stimulation of the peripheral trunk in certain kinds of
animals reduces the volume of the lung, which can only be due
to the contraction of the smooth muscles of the bronchi, is very

FIG. 202. — Effect of dividing phrenics in dog. (Lnciani.) To, intrathoracic pressure ; Ca, carotid
pressure. A-B, previous to section of phrenic ; B-C, after section. The tracing shows that
both inspiratory and expiratory movements are exaggerated after section.

striking. Eoy, with Brown, and Sandmann claimed to have also
discovered dilator bronchial fibres in the vagus, the action of
which is expressed by pulmonary dilatation, when the peripheral
end of the vagus is excited with strong currents. It is not
improbable that the presence of these dilator fibres in many cases
weakens or nullifies the effect of the simultaneous excitation of
the constrictor fibres, which would account for the negative result
obtained by some observers.

Division of the vagi in the horse causes a considerable increase
of volume in the lung, a proof that the constrictor fibres of the
bronchi in these animals are in constant or tonic excitation. In
dogs, on the contrary, section of the vagi produces a scarcely
perceptible dilatation of the lung, showing that there is only weak
tonic excitation.

According to some interesting observations of Fano and Fasola,
the lungs of the marsh tortoise are capable of very extensive
active movements, due partly to the smooth muscle cells which

xiii EESPIEATOEY EHYTHM 443

are innervated by the vagus, partly to the striated fibres derived
from the muscles of the diaphragm, which penetrate the
parenchyma of the lungs, to invest the large alveoli, and are
innervated from the spinal nerves. When the vagus is stimulated
in the neck of this animal, a curve of slow prolonged contraction
is obtained from the lung, exactly similar to that served up by
smooth muscle. When, on the other hand, the spinal cord is
excited, a rapid pulmonary contraction results, which is evidently
due to the striated muscles.

The physiological function of the smooth muscles of the-
^bronchi, and of the constrictor and dilator nerves which serve
them, is not yet fully explained. It seems obvious that they give
greater resistance to the bronchial walls, and reinforce this resist-
ance by their contraction, when the negative intrathoracic pressure
falls too low, during forced inspiration. Probably the development
of the pulmonary emphysema is promoted by atony, or by the
paresis or paralysis of the smooth muscles.

II. As a whole the central mechanisms, from which the
several motor nerves to the respiratory muscles receive their
rhythmical impulses, must be excessively complicated, seeing that
the co-ordination of the inspiratory and expiratory movements,
i.e. the harmonious and synergic contraction of the muscles which
alternately expand and contract the thorax, depend upon them.
The immediate centres for the motor respiratory nerves must,
however, be distinguished from the true controlling and co-
ordinating respiratory centre. The former lie in the cervico-
dorsal tract of the spinal cord, and are formed from the grey
matter of the anterior horns, which contains the nerve cells of
which the nerves to the respiratory muscles are the prolongation ;
the second is situated in the medulla oblongata, and has probably
no direct influence upon the muscles, but is confined to exciting
and regulating the functions of the former.

When the brain is extirpated to the level of a plane which
. passes along the inferior limit of the pons, or when a section is
made at the level of this plane, it will be seen that after temporary
disturbance the animal continues to breathe spontaneously, in a
regular and perfectly co-ordinated manner. This experiment
proves that the co-ordinating centre for the respiratory movements
does not lie higher than the spinal bulb. When, on the contrary,
the bulb is divided from the cervical cord at the apex of the
calamus scriptorius by a transverse section, the respiratory move-
ments ipso facto come to a standstill. This proves that the
respiratory centre lies within that section of the bulb which is
situated between the two planes of division indicated.

Which portion of the bulb is it, however, which represents
the respiratory centre ? The experiments directed towards the
localisation of this centre have a very involved history, which

444 PHYSIOLOGY CHAP.

must be recapitulated in its principal headings. Galen already
knew that a section through the highest part of the cord produced
the immediate death of the animal. " Perspicuum est, quod si
post primam aut secundam vertebram, aut in ipso spinalis medullae
principio sectionem ducas, repente animal corrumpitur" (De
anat. administr. lib. viii. cap. ix.).

This experiment was successfully repeated in 1760 by Lorry,
arid perfected in 1811 by Legallois, who at a later time showed
experimentally on the rabbit that " respiration depends upon a
very circumscribed region of the medulla oblongata, which is
situated at a short distance from the occipital sulcus, and near the
origin of the eighth or pneumo-gastric nerves."

A few years later (1842) Flourens took up these experiments
of Legallois, and endeavoured to localise the respiratory centre
more exactly, but he added nothing substantial to the results of
Legallois. In a subsequent communication (1851) he defined as
point, ou nceud vital a very minute tract of grey matter, the size
of a pin's head, lying in the median line towards the tip of the
calamus scriptorius, ablation of which infallibly led to the
immediate death of the animal.

It was, however, shown by Volkniann (1842), Longet (1847),
and M. Schiff (1858) that the respiratory centre is a double
organ, which can be divided by a median longitudinal section
down the sinus rhomboidalis into two halves, without causing
arrest of respiration by the section. After these publications
Flourens also (1859) recognised that the nceud vital is double,
and that in order to destroy life " a transverse section of 5 mm. is
required, passing through the centre of the V. of grey matter in
the medulla oblongata," i.e. half way up the beak of the calamus
scriptorius.

Longet, and even more definitely Schiff, endeavoured to show
that the true respiratory centre is located in the large nucleus of
grey matter in the alae cinereae, which lies in the lower part of
the bulb, external to the nucleus of the hypoglossus, beneath the
floor of the fourth ventricle, and that the paths by which the
impulse is conducted thence to the spinal cord run in the lateral
bundles, unilateral section of which, at the lower level of the bulb,
or at the level of the second and third cervical vertebrae, suffices
to produce respiratory paralysis of the muscles of the same side
(Schiffs respiratory hemiplegia). The animal may survive this
operation for weeks and months, and active movements of
respiration never reappear on the operated side (1854).

This last fact suffices to refute Brown-Sequard, who in 1858
denied the existence of a bulbar respiratory centre. In his opinion,
the sudden death of the animal after lesion of the bulb was the
effect, not of paralysis or deficiency, but of traumatic excitation of
an inhibitory centre or the paths for the respiratory movements.

XIII

EESPIEATOEY EHYTHM

445

If this were correct, the respiratory hemiplegia consequent on
unilateral division of the lateral bundles in the upper cervical
region would disappear after a short time. It is, however, true
that with great care the whole of the so-called nceud vital of
Flourens, as also, according to Schiff, the whole internal or median
half of the ala cinerea can be destroyed, without producing
permanent arrest of respiration. It is only when the external
half of the ala cinerea is separated from the central grey matter
that respiration on the corresponding side is abolished for ever.

FIG. 203.— Section of spinal bulb in man at level of exit ot vagus and hypoglossal nerves— from the
section. (Lueiana.) Crst Rectiform body ; Nfc, nucleus of funiculus cuneatus ; Villa, ascending
root of auditory nerve ; NX, nucleus of vagus, which appears as ala cinerea at surface of
rhomboidal sinus ; NXII, nucleus of hypoglossal ; Nm median nucleus (or nucleus of funi-
culus teres) ; IXa, ascending root of glosso-pharyngeal (or funiculus solitarius) ; Fr, formatio
reticularis ; R, raphe ; SgB, substantia gelatinosa Rolandi ; Va, ascending root of trigeminal ;
X, vagus ; Na, nucleus ambiguus ; Oae, accessory external olive ; Ooa, accessory anterior
olive; 0, olive ; XII, hypoglossal; L, fillet; Py, pyramidal bundle; Narc, arciform
nucleus

From these facts (which were confirmed in the last years of his
life by Schiff, and by his pupil Girard) we must conclude that the
most indispensable part of the respiratory centre lies within the
outer half of the ala cinerea, bordering on the median limit of the
restiform body, i.e. external to the dorsal or sensory nucleus of
the vagus and glosso-pharyngeal, along with the solitary bundle,
and the dorsal and distal portion of the formatio reticularis
(Fig. 203).

In the year 1873 Gierke, under Heidenhain's direction,
carried out a series of experiments with a view to determining

446 PHYSIOLOGY CHAP.

more exactly in which section of the bulb lesions brought
about a sudden respiratory standstill. He carefully located the
site of the bulbar lesions inflicted during the life of the animal, by
microscopic examination of the hardened and stained preparations.
He found that the arrest of the respiratory movements was
invariably determined by the division, or at any rate the injury, of
the solitary bundle, which he regarded as the respiratory centre
proper, since it consists of a column of small multipolar nerve cells,
mingled with nerve fibres.

Gierke's results do not contradict those of Schiff, since it is
impossible to divide the solitary bundle without at the same time
destroying the external, deep section of the dorsal nucleus of the
vagus or the nerve fibres descending from it. It is only the
interpretation of the results that differs.

In 1892 Gad and Marinesco published a series of interesting
experiments on the slow and gradual destruction of the floor of
the fourth ventricle by the method of repeated punctiform cauterisa-
tion by fine glass rods, rounded and heated at the end, which
avoided haemorrhage, traction, and pressure on the adjacent parts.
By these experiments, undertaken with the utmost precaution,
they were able to destroy not only Flourens' nceud vital at the
apex of the calamus scriptorius, but also the external portion of
the ala cinerea, including the solitary bundle, without finally
bringing respiration to a standstill. They frequently noted
respiratory disturbances and even arrest, due to excitation of
inhibitory paths, which soon passed off, and permitted them to
proceed cautiously with the cauterisation. Only when the lesion
was prolonged deep into the formatio reticularis was there final
arrest of respiration. In addition to the respiratory tracts,
descending to the spinal centres, the formatio reticularis contains
a number of cells, which, although few in number, and not grouped
into a nucleus, may very well as a whole represent the respiratory
centre. At the same time it is not necessary to destroy the
whole of this formation to obtain immediate arrest of respiration.

With Deiters, Gad distinguished that part of the formatio
reticularis, which lies medially to the root of the hypoglossus and
extends to the raphe, from the lateral part which lies outside this
root. In rabbit it is only necessary to injure this last segment
deeply enough, in order to produce permanent arrest of the
respiratory movements. In the cat, on the other hand, the same
result is obtained by cauterising the part which lies between the
root of the hypoglossus and the raphe. In any case, whatever
segment of the formatio reticularis is destroyed, it suffices, if not
to bring about total arrest of the respiration, invariably to produce
a considerable weakening in respiratory energy. It is therefore
probable that the whole of the formatio reticularis (which as a
unit includes a much more extensive segment of the bulb than the

xni KESPIKATOEY EHYTHM 447

nceud vital of Flourens) constitutes the bulbar centre of respira-
tion. Evidence for this theory is given, according to Gad, in the
fact that very circumscribed electrical excitation by means of fine
needles, varnished as far as the points, and thrust into the parts of
the formatio reticularis which lie above and beneath those parts
whose destruction produces respiratory arrest, provokes only an
acceleration of respiratory rhythm, and not a tetanus of the
inspiratory muscles, as occurs when the respiratory tracts in the
lateral bundles of the cervical cord are excited.

Whatever the extension of the true bulbar respiratory centre,
it is certain that the symmetry of the respiratory movements on
the two sides of the thorax depends on the intrabulbar commissural
fibres, which unite the two lateral halves of the respiratory
centre ; and that the descending paths, which unite the bulbar
centre with the spinal centres of the respiratory muscles, and run
directly, without decussating, in the lateral bundles and in the
highest portion of the cervical region, are probably located in the
processus reticularis, which lies between the anterior and posterior
horns of the grey matter of the cord.

III. We have already seen that Brown-Sequard, in 1858,
denied the existence of a bulbar respiratory centre, and interpreted
the results of Flourens' experiments as inhibitory phenomena, by
which the rhythmic activity of the spinal centres, the sole cause
of the respiratory movements, were suspended. The successful
destruction of the so-called nceud vital without abolishing respira- I
tion seemed to justify his opinion. Now, however, we know that I
the noeud vital does not constitute the whole of the bulbar ;
respiratory centre, which is much more extensive, and apparently 1
comprises the entire formatio reticularis. /

In 1880 Langendorff attempted to resuscitate the doctrine of
Brown-Sequard, in Germany, on the strength of an interesting fact
discovered in 1874 by P. Eokitansky. He saw that in young
rabbits it is possible for a certain time to revive the respiratory
movements suppressed by separation of the bulb from the
spinal cord, after suspending artificial respiration and slightly
strychninising the animal, to increase the excitability of the cord.
Schroff confirmed this in 1875, adding that in order to reinstate
some respiratory movements in animals with divided bulb, without
employing strychnine, it was only necessary to avoid cooling
during artificial respiration by keeping the animal in a warm
chamber. Langendorff (1880)- further found, after dividing the
bulb, that natural respiration was reinstated for a considerable
time in newborn puppies and kittens without resorting to
adventitious aids other than artificial respiration. Since it is
well known that in the newborn, as in the lower animals, the
functions of the spinal cord exhibit a far greater degree of
autonomy and independence of the higher centres than in the

448 PHYSIOLOGY CHAP.

adult, Wertheinier (in 1886) endeavoured in France to repeat
the same experiments on adult animals by prolonging artificial
respiration for f-2 hours after section of the bulb, in order to give
time for the supposed traumatic inhibition to pass off. He
observed that at the close of artificial respiration the animals
made certain movements of the thorax, abdomen, and limbs, which
produced a kind of pulmonary ventilation, and kept them alive for
a considerable time, even in some cases for three-quarters of an
hour.

On the whole, no definite conclusions as to the independence
of the spinal respiratory functions from the bulb can be deduced
from these experiments. There is no proof that the movements of
thorax and abdomen observed under the above conditions after
division of the bulb, are co-ordinated like normal inspirations and
expirations ; in fact, it appears from Wertheimer's own observations
that they are irregular and inco-ordinate. Often they are simple
active abdominal expirations, followed by passive inspirations ; at
other times the inspirations are associated with repeated expira-
tions, which cancel their mechanical effects, and look like double
or triple inspirations. Very frequently the thoracic and abdominal
movements are associated with other movements of the limbs, tail,
and vertebral column, due to spread of excitation from the spinal
centres. The long survival period in animals with divided cord
may also be due to the marked fall of temperature, caused by the
prolonged artificial respiration by which the animals are reduced
to the poikilothermic or hibernating condition, in which they
are able to survive for a long time with minimal renewal of
pulmonary air.

Langendorff endeavoured to sustain his theory of there being
only an inhibitory and regulatory centre for respiratory move-
ments in the bulb — their activity being due solely to the spinal
centres — by showing that mechanical, electrical, and chemical
stimulation of the floor of the fourth ventricle, in chloralised
rabbits, induced phenomena of respiratory arrest, which ceased
with the excitation.

On the other hand Kronecker and Marckwald (1887-89), on
repeating the experiments with rabbits in which the spinal bulb
was separated from the cerebrum, obtained quite opposite results.
Respiration was accelerated by electrical stimulation of the bulb,
which also caused respiratory movements, intercalated between
those made by the animal. This was confirmed by Aducco (1889)
on intact and non-anaesthetised dogs, both with electrical excita-
tion of the sinus rhomboidalis (Fig. 204), and with its chemical
excitation by a crystal of sodium chloride.

The effects of applying cocaine to the bulb, as determined by
Aducco's experiments, are even more striking. When, e.g., cocaine
hydrochloride (either in the form of crystals, or as a powder mixed

XIII

EESPIEATOEY EHYTHM

449

with vaseline) is applied to the floor of the fourth ventricle, it is
seen after a few seconds or minutes, according to the rapidity of
absorption, that all respiratory movements cease and the thorax is
fixed in the cadaveric posture. This paralysis of the respiratory
movements is preceded by a brief period of excitation, in which
the inspiratory movements are exaggerated. Quite different effects
are obtained on the heart, the beats being accelerated directly after
the application of the poison, as after section of the vagi, or intoxi-
cation with atropine, an effect that persists after the respiratory
standstill. When the cocaine hydrochloride is applied in the form
of an ointment, so that the poison is more slowly and gradually

FIG. 204. — Effects of weak (A) and medium (B) electrical excitation of spinal bulb in dog.
(Aducco.) Excitation from a to w. R, Respirations recorded with Marey's pneumograph ; P,
arterial pressure traced with Marey's metal manometer ; s", seconds. The inspiratory effects
are seen on both tracings.

absorbed, different phases of modification may be distinguished in
the respiratory and cardiac movements. Fig. 205 shows the
curves of normal respiration and heart-beat in the dog ; there are
four respirations and eighteen heart-beats in 20 seconds. One
minute after applying the cocaine to the floor of the fourth
ventricle the curve of Fig. 206 is obtained, which shows five less
ample respirations and^tliee beats in 20 seconds. Nine minutes
after applying the poison the form of respiration is entirely altered
(Fig. 207) and has become quite slow. The line of rest of the
thorax corresponds with the extreme inspiratory position, which
is due, not to an inspiratory tetanus, but to the fact that the ex-
pirations only are active, while the inspirations are passive, i.e. they
represent the elastic recoil of the thorax to the position of
VOL. I 2 G

450

PHYSIOLOGY

CHAP.

equilibrium at the close of expiration. The acceleration of the
cardiac movements persists; thirty-eight beats may be counted
in 20 seconds. Ten minutes from the commencement of the

PIG. 205. — Normal tracings of respiration (R) and carotid pulse '(1}) in a .dog after exposing the
rhomboidal sinus. (Aducco.) R, Tracing recorded with Marey's pneumograph ; P, with
Marey's metal manometer ; .<<", with L)eprez signal.

experiment the active expirations also cease, and the animal
quickly succumbs to asphyxia, unless artificial respiration with
the bellows is resorted to.

FIG. 206. — Same as preceding, one minute after applying O'o grm. cocaine ointment to floor of
4th ventricle. (Aducco.)

The paralysing action of cocaine on the bulbar centres was con-
firmed by Aducco with the addition of a highly characteristic
group of effects; enormous dilatation of pupil, insensibility of

xni KESPIRATOEY EHYTHM 451

conjunctiva, immobility of pupil, inertia and flaccidity of tongue
and muscles of jaw, suppression of salivary secretions, marked fall
of temperature, inhibition of swallowing reflexes, failure to vomit
after injection of apomorphine ; lastly, suspension of any kind of
reaction from the cocainised bulbar substance to electrical stimuli,
however strong. The possibility that under these conditions there
can be paralysis of the spinal, as well as the bulbar centres, owing
to spread of the poison, seems to be excluded by the rate at which
complete arrest of respiratory movements may occur (less than
20 seconds), as well as by phenomena which prove that the
excitability of the spinal centres is maintained — e.g. rhythmical
contraction and relaxation of the sphincter on introduction of the
finger into the rectum.

These results led Aducco to the important conclusion that a
true motor centre exists in the bulb, besides the inhibitory centre

FIG. 207. — Same as preceding, after nine minutes' application of the drug. (Aducco.) Tracing
R shows the active and passive inspirations. Followed by complete arrest of respiration.

to the heart, and that both are paralysed by the local action of
cocaine. The paralysis of the cardiac inhibitory centre (formed as
we have seen by the nuclei of origin of the accessory) causes
acceleration of the beats ; paralysis of the respiratory centre
(constituted in all probability by the formatio reticularis) causes
arrest of respiratory movements. Hence it is the bulbar respiratory
centre that sends co-ordinated rhythmical impulses to the spinal
centres of the respiratory muscles. These last centres are, therefore,
incapable of any rhythmical activity, independent of that of the
bulbar centre. If under certain conditions (as in the experiments
of Langendorff, Wertheimer and others) they show activity
independent of the bulb, this activity, is not co-ordinated, and is
conditioned by the peripheral or central stimuli, of which we have
still to study the mechanism.

The simplest, clearest, and most incontrovertible proof of the
absolute dependence of the spinal centres of the respiratory

Ts

Td

452 PHYSIOLOGY CHAP.

muscles upon the controlling bulbar centre appears, however, in
the fact that permanent respiratory hemiplegia ensues on unilateral
section of the upper cervical cord (Fig. 208). Schiff rightly-
directed attention to this fact in his last work on the respiratory
centre (1894), in order to refute the old doctrine of A Brown-
Sequard as tentatively revived by Langendorff and Wertheimer.

It is, however, still uncertain whether we should, with
Langendorff, admit the existence of another autonomous inhibitory
centre for respiratory movements, along with the controlling
centre in the bulb. Laiidergreen's studies on the circulatory and
respiratory phenomena in asphyxia (1897), those of Prevost and
Stern on the final respirations (1906), and, lastly, those of Mosso
on the asphyxial pause, contain no conclusive arguments for or
against the theory of an inhibitory, respiratory, bulbar centre.

Patrizi and Franchini, on the ground of certain peculiarities of

FIG. 208.— Pneumograms of most convex part of right (Ts) and left (Td) half of thorax in young
hound, operated on three weeks previously by hemisection of cord at level of highest cervical
tract. (M. Schiff.) The slight respiratory movements of the right half of the thorax are
passive, i.e., they depend on the aspiration of the mediastinum to the left dne to elevation of
sternum.

respiratory arrest from centripetal excitation of the vagus (1906-7),
are inclined to admit LangendorfFs contention. The question is a
difficult and complex one, and will require extensive experimental
researches before we can hope for its solution.

IV. It is doubtful whether the bulbar respiratory centre, and
the spinal respiratory centres scattered along the cervico- dorsal
tract of the spinal cord, really represent the whole of the central
nervous mechanisms which take an active part in bringing about
the mechanical processes of respiration. In all probability, we
must, in addition to the bulbar and spinal centres, also admit the
existence of true respiratory centres in the brain.

We know that the respiratory mechanism can be modified in a
variety of ways, both by voluntary impulses and by simple
psychical emotions. A practised singer has such perfect control
over his own respiratory movements that in expelling the air from
his lungs he is able to produce the finest shades of tone during
expiration. Again in conversation, and still more in oratory, the

xin EESPIKATOEY EHYTHM 453

necessity for breathing is relieved by devices very far from ordinary.
The inspirations are taken at rare intervals, and are deep and
quickly completed ; they occur at irregular intervals, and at
moments when the phonetic pauses are effective in expression ; the
expirations, on the contrary, are prolonged and often very power-
ful, since the expired air is employed wholly in the service of
phonetic expression. So, too, in sucking, swallowing, vomiting,
defaecation, and parturition, the mechanics of respiration (as we
shall see elsewhere) assume different forms and attitudes. Laughing,
crying, sobbing, yawning, represent so many typical expressions of
feeling, which all, as we have seen, consist essentially in special
forms of the respiratory, movements. Fear, joy, expectation, pre-
occupation, are states of mind continually associated with
respiratory changes, which are conspicuous enough, even if less
characteristic than the preceding. The direct control of the will
is only exerted upon the respiratory movements under quite special
conditions — e.g. we hold our breath when we know the air to be
foul or stagnant, when we dive into water, or under other similar
conditions.

All these psychical modifications of the respiratory rhythm are
governed by impulses emanating from the cerebral cortex,
particularly from that region known as the motor area. AVhen
this tract is stimulated electrically in the dog or cat, the respiratory
movements are visibly accelerated or retarded, which depends less
on the seat than on the intensity of stimulation. According to
Fran^ois-Franck, strong stimuli retard the respiratory processes ;
weak stimuli accelerate them.

The sub-cortical centres are also capable of modifying respiratory
rhythm. On exciting the surface of a section, at the level of the
anterior and posterior corpora quadrigemina, Martin and Bocker
obtained unmistakable inspiratory effects. Christian! found the
same on exciting the floor of the third ventricle. When, on the
other hand, he excited the grey matter, at the entrance of the
Sylvian Aqueduct, he obtained expiratory effects.

These different parts of the brain (and probably others not yet
investigated because less accessible) affect the respiratory move-
ments, in so far as they are capable of modifying the rhythmical
activity of the bulbar respiratory centre, with which they are
connected by means of special descending nerve tracts. Evidence
for this is afforded in the fact that the clean division of brain
from bulb at the level of the upper limit of the pons, has, as we
have seen, only a transient effect on respiratory rhythm. This
shows that even under normal conditions the cerebral respiratory
centres take no active part in modifying the impulses sent out
from the bulbar centre. We shall, however, see under what
abnormal circumstances the influence of the cerebral respiratory
centres is functionally apparent in its full importance.

454 PHYSIOLOGY CHAP.

The complete nervous system on which the respiratory
mechanism depends may thus be divided into three sections : the
bulbar, the spinal, and the cerebral respiratory centres. From the
first emanate the rhythmical impulses to thoracic - abdominal
movements on which the activity of the spinal respiratory centres
which pass the impulses on to the muscles depends ; but the
rhythmical activity of the bulbar centres is in its turn regulated,
and may be modified in a number of ways, by the cerebral
respiratory centres.

V. In order to form a more adequate conception of the mode
in which these highly complicated systems function, it must be
remembered that we understand by the term respiratory centres
an accumulation of central mechanisms, which are capable of a
double and antagonistic action — one inspiratory, which dilates the
thorax, the other expiratory, which contracts it. As we have seen
in the preceding chapter, both forms of movement are active and
are brought about under normal conditions by the contraction of
antagonist muscles; we cannot regard expiration as the simple
effect of inhibition acting upon the inspiratory centres, but must
further assume the existence of true expiratory centres* The
concept respiratory centre thus implies the association of two
centres, which have an opposite function in respect of pulmonary
ventilation, and can, therefore, under normal conditions, only
function rhythmically and alternately.

Not only must we recognise the existence of expiratory centres
as distinct from inspiratory centres ; on the ground of irrefutable
observations we must further admit that these centres, while
normally associated in their rhythmical and alternating functions,
are yet capable under abnormal conditions, particularly the
influence of certain poisons, of functioning independent of each
other. That the inspiratory centres may, under special circum-
stances, alone be active will readily be admitted by all (and these
^ form the vast majority) who hold that, normally, inspirations, alone
are active. But it is also possible to demonstrate that under
various other conditions the converse holds good, the expirations
, only being active, while the inspirations are passive. In these
, cases the inspiratory centres do not function, and the expiratory
centres alone perform their work. Inspiration is effected by the
elastic recoil of the thoracic walls, which are pushed below their
resting position.

Aducco succeeded in collecting certain observations and
recording them graphically enough to establish this fact, which as
a contribution to the theory of the centres that control the
mechanics of respiration is of no small importance. The curves of
Fig. 209 were recorded by two tambours with exploring buttons
(applied to the sternum and the linea alba abdominis respectively,
their movements being transmitted to two other tambours writing

XIII

EESPIEATOKY EHYTHM

455

on a revolving drum) from a tracheotomised dog which had 3
grms. of chloral hydrate injected in several doses into its jugular
vein. Under these conditions there are seen to be a few active
abdominal expirations, in which one very energetic and one
shallow effort alternate with tolerable regularity. All the

FIG. 209.— Thoracic (T) and abdominal (A) pneumograms obtained from two exploring button
tambours on a dog, after intravenous injection of 8 grms. chloral hydrate. (Aducco.) The
descending curves of A correspond to active abdominal expirations. The slight movements
of T are passive.

respiratory processes depend upon these rhythmical abdominal
respirations which pull upon the thoracic walls, on which the
traction of the rectal abdominal muscles follows passively. In
this case, therefore, the
chloral succeeds (tempor-
arily at least) in paralys-
ing the rhythmic activity
of the thoracic inspiratory
and expiratory centres,
while maintaining and
even increasing the action
of the expiratory centres
for the abdominal muscles.
In other cases (in which
the specific mechanism of
action is unknown) the
chloral paralyses both the
inspiratory and expiratory
abdominal centres, and
increases the rhythmical
activity of the thoracic expiratory centres. Thecurvesof Fig. 210were
taken from a tracheotomised dog, after injecting 5 grms. of chloral
hydrate into the jugular vein. It will be seen that the resting
position of the thorax coincides with the end of inspiration and
commencement of expiration ; between the first and second there is
a pause, after which a marked depression of the thorax occurs, which

pio> 210._Tracing, as iu last flgunji Prom dog after

intravenous injection of 5 grms. of chloral hydrate.
(Aducco.) The descending lines of tracing T coincide
with active thoracic expirations, followed immediately
by the ascending lines of passive inspiration. The

^verste abdominaf moveillents (A) are passive.

456 PHYSIOLOGY CHAP.

produces a passive rise of the abdominal wall, and thus drives the
air out of the trachea. Active thoracic expiration is immediately
succeeded by passive inspiration, in which the thorax rises again,-
and the abdomen falls.

These exceptional phenomena, with the cause of which we are
unacquainted, and which accordingly cannot be determined
experimentally, have no physiological significance other than that
of showing the existence of an expiratory centre, which can
function separately when the inspiratory centre is put out of court.
Moreover, these and other facts investigated by Aducco show that
in the dog forced expiration is no functional unity, effected always
in the same way, and by the help of the same mechanism. It
may be carried out by the walls of the thorax or by the walls of
the abdomen. In the abdomen itself, according to Aducco, it is
possible to separate two expiratory mechanisms — the interior recti,
and the lateral muscles. These different expiratory mechanisms
(thoracic, and anterior and lateral abdominal) may function
simultaneously or synchronously — or simultaneously and a-
synchronously, — or lastly, separately from one another. •

Other similar phenomena, noted incidentally by various
authors (Hering and Breuer, Luciani, Stefani, and Sighicelli, &c.),
but which Mosso (1878-1885) specially emphasised, show that the
inspiratory centre, too, may be regarded as an aggregate of centres,
which, although they normally function harmoniously, while each
retains a certain degree of autonomy and independence, may yet,
under certain indefinable conditions, come into play at different
times, act with unequal intensity, and even be capable of func-
tioning separately. According to Mosso, we must at any rate
accept a facial, a thoracic, and a diaphragmatic centre for inspira-
tion, since on comparing the simultaneous tracings from the three
different groups of muscles, a-synchronisms or different intensities
of action can be detected at different times upon the same
individual. The most striking fact of this kind is that in sleep
respiration is essentially costal, since (as shown in another con-
nection, Fig. 184, p. 418) the diaphragm is virtually inactive. In
the death-agony, on the contrary, the opposite prevails ; only the
'diaphragm is active, while the intercostal muscles are paralysed.
We must conclude that in sleep the thoracic and diaphragmatic
inspirations coincide, the first, however, outlasting the second : at
other times thoracic inspiration precedes the diaphragmatic.

From these and other similar facts Mosso concluded that " the
earlier conception of a single respiratory centre must be abandoned ;
the respiratory movements of the facial muscles, diaphragm,
thorax, and abdomen have their specific nerve centres, which
function autonomously." Schiff, in his last work (1894), criti-
cised this attempted decentralisation of respiratory innervation.
According to him the special centres of the spinal cord, on which

xiii RESPIRATORY RHYTHM 457

depend the contractions of the different groups of muscles that
serve in respiration, are not true respiratory centres, since lihey
are not perfectly autonomous, and require a co-ordinating centre in
the bulb, which is the sole organ on which respiratory stimuli act,
and is alone capable of elaborating them so as to throw the spinal
centres into activity. He opposes the theory of decentralisation
by one of centralisation. The difference between the two theories
seems, however, to lie in the name rather than in the conception.
In. our opinion the real problem (which has so far remained
unanswered) is the more exact definition of the nature of the
co-ordinating function of the bulbar respiratory centre. Do the
various modes of functional association and succession of the
several muscles or groups of respiratory muscles depend exclusively
on this ; or do the respective spinal centres also co-operate actively ;
or (at the least) is the varying degree of excitability of these centres
at the given moment in which they receive the impulses from the
bulbar centre, of account ?

Nothing definite, again, is known as to the localisation of the
supposed subordinate inspiratory and expiratory centres. We
only know that in both categories we must distinguish between
the centres of the cerebral, bulbar, and spinal segments, which
enormously complicates the problem of their localisation.

VI. In view of the well-established fact that under normal
vital conditions, with the senses and all the mental emotions at
rest, the respiratory movements are completed involuntarily, in
consequence of rhythmically alternating impulses, from the
inspiratory and expiratory bulbar centres, the question arises
whether these impulses are automatic or reflex in character, i.e.,
whether they are the effects of rhythmical changes intrinsic to the
centres, or depend upon rhythmic or continuous stimuli, coming
to them from without ? In order to determine this point, which
is of fundamental importance, we must first of all examine how
they are affected by the various afferent nerves, with which they
are in direct anatomical and physiological relation. Among these
in the first place is the Vagus.

The cervical trunk of every vagus nerve contains afferent
fibres coming from the lung, and passing to the bulbar respiratory
centre. From the terminal ramifications of these fibres in the
lungs, rhythmical excitations pass to the centres, and are capable
of throwing them into activity, or considerably modifying their
intrinsic energy. This is clear from the experimental researches
of Rufus of Ephesus, Galen, and Legallois (1812).

When the trunk of one vagus is suddenly divided in the neck,
while the animal breathes air regularly from a large closed cylinder,
connected with a Marey's writing tambour, which registers the
oscillations of tracheal pressure, the respiratory type changes ipso
facto ; the breathing becomes more excursive and less frequent,

458

PHYSIOLOGY

CHAP.

without previous suspension of respiration, or gradual alteration in
the transition from one type to another. The same effect appears
after cutting the second vagus, but in a more accentuated form ;
immediately after section the breaths become extremely dyspnoeic
and infrequent. In rabbit these effects are less marked than in
the dog, as appears from the curves of Fig. 211 (Luciani, 1879).

-According to Gad (1880) these results are not simply the
expression of cutting out the vagus action on the respiratory
centres, since in dividing the nerve mechanical stimulation from
the operation is inevitable, as well as excitation from the demarca-
tion current set up in the injured trunk. He proposed to nullify

FIG. 211. — Effects of vagus section on respiratory rhythm on rabbits (AA') and dogs (BB').
(Luciani.) The right vagi were cut at TI, the left at T%. In A and A' a large rabbit breathed
from a closed vessel, containing 12 litres of air. communicating with a writing tambour.
In B, B' a small dog breathed from a receiver of 30 litres air.

the function of the vagus, by lifting it over a metal rod cooled
below zero, when the nerve would freeze suddenly at the point of
contact, and lose its conductivity, without producing excitation.
The results obtained with this more elegant method, however,
differed little from our own results with simple division, apart from
the fact that the inspirations alone became more ample, while the
expirations were maintained at the same height as before, or even
fell below it, as shown by Fig. 203. Even this difference was only
shown in the rabbit ; in the dog both inspirations and expirations
were increased..

These effects, which follow directly on the abolition of vagus
influence upon the respiratory centres, are not associated with any

xin EESPIEATOKY EHYTHM 459

conspicuous changes in the amplitude of respiration, or degree
of pulmonary ventilation in the time-unit. According to Gad,
after freezing the vagi the amplitude of respiration undergoes a
slight diminution ; according to Lindhagen, on the contrary (in
agreement with our own observations), it remains almost un-
altered ; this means that the increased depth of the respirations
almost perfectly compensates for the diminution in frequency.

From these facts we may deduce the important conclusion
that the vagi reflexly exert a marked regulatory influence upon
the respiratory centres. The respiratory type witnessed after
suppression of this influence is, as justly remarked by Gad, very
ill-adapted for its purpose, since the respiratory effort is con-
siderably greater, while its utility, as represented by the respiratory
volume, is not increased, and may even be diminished. It is in
fact from the ratio between force and effective utility that we
must judge of the degree of adaptation. If with intact vagi the

FIG. 212.— Effect of freezing the vagus on respiratory rhythm of rabbit. .(Lindhagen.) The rabbit
breathes from receiver of Fig. 187 (p. 422). The vertical line marks the moment at which the
vagi were frozen. The lower tracing marks seconds.

play of the respiratory muscles is modified, this obviously means
that they reflexly regulate the respiratory rhythm in such a way
that the same effect is obtained with far less effort, and witli-
minimum expenditure of energy.

In 1868 Hering and Breuer, in an important series of experi- V
ments, attempted to elucidate the mechanism of this regulation of
the respiratory processes by the vagi. They found on animals
that any dilatation of the lungs, produced no matter by whaW
means, checked the inspiratory and promoted the expiratory act ;
whatever, on the contrary, caused contraction of the lungs,/
inhibited expiration and determined inspiration. After vagotomy,
these effects ceased altogether; the respiratory rhythm assumed
the type described above, which undergoes no modification with
reference to the state of contraction or dilatation into which the
lungs are artificially thrown. The results of Hering and Breuer
may be recapitulated the better to define their effects, and bring
out their importance : —

460 PHYSIOLOGY CHAP.

(a) If on a tracheotomised rabbit, with intact vagi, breathing
normally, rhythmical insufflations (positive ventilation) or
rhythmical aspirations of air (negative ventilation) are made
through the tracheal cannula, so that in the first case rhythmical
dilatation, and in the second, rhythmical retraction of the lungs, is
produced, it will be seen that the animal reacts to each insufflation
by an expiration, as plainly shown by the constriction of the nasal
pinnae, and to each aspiration of air by an inspiration, as evidenced
by the widening of the nostrils. If the insufflations or aspirations
are retarded or accelerated, the animal adapts its respiration to the
required rhythm by making the opposite movement, i.e. it reacts
with an expiration to each dilatation, with an inspiration to each
contraction of the lungs. This harmony between natural and
artificial respiration ceases absolutely after section of the vagi. -

(6) If the rubber ring attached to the tracheal cannula of an-
•animal (with intact vagi and regular respiration) is constricted or
occluded at the moment at which expiration ceases and inspiration'
sets in, it will be seen that the latter lasts far longer. If, on the
contrary, the trachea is constricted or occluded at the close of an
inspiration and commencement of an expiration, the animal is
seen 'to extend its expirations and remain longer in the expiratory
posture. These effects cease after section of the vagus..

(c) When a ventilating apparatus is attached to the tracheal
cannula of a dog or rabbit, which favours inspiration and hinders
expiration, so that the extent of pulmonary distension increases at
each inspiratory act, it is seen that the expiratory acts consequent
on the successive inspirations become longer and more energetic,
until the tetanic force of the expiratory abdominal muscles ejects
the ventilating apparatus from the cannula.

(d) If in an animal with normal respiration, double pneumo-
thorax is suddenly produced by opening the two pleural cavities,
the vagi being intact, a deep and prolonged inspiration follows — a
true inspiratory tetanus.

(e) Similar facts are met with clinically, when in consequence
of any kind of morbid condition the expiratory retraction or
inspiratory dilatation of the lungs encounters some obstacle. In
the first case (e.g. in pulmonary emphysema) expiration, in
the second (e.g. stenosis of the larynx or trachea, plural or peri-
cardial effusions, etc.) inspiration, is prolonged.

In the year 1888 Stefani and Sighicelli (in continuation of the
researches of Hering and Breuer) endeavoured to determine what
changes in respiratory rhythm occurred when a rabbit was made
to pass rapidly from breathing air under normal pressure to
respiration at higher or lower pressures, so that the lungs became
passively dilated or contracted. The method consisted in applying
a T-cannula with a three-way tap to the animal's trachea. One
of the outer branches of this cannula communicated freely with

xiii KESPIKATOEY EHYTHM 461

the external air, the other was connected with a receiver containing
more or less condensed or rarefied air. A turn of the tap was
sufficient instantly to change the connection of the lungs from
atmospheric to rarefied or condensed air.

The results obtained by this method do not seem substantially
to contradict those of Hering and Breuer. The transition from
free to compressed air provokes a short or prolonged expiration,
according as the rise of pressure causes marked or slight expansion
of .the lungs. Transition from free to condensed air induces an
inspiration more or less deep or prolonged, according as the
diminution of pressure evokes a slight or pronounced contraction
of the lungs.

On the strength of the facts enumerated above, Hering and
Breuer propounded the so-called theory of the automatic regulation
of respiration, which consists in the assumption that the respiratory
movements comprise a respiratory mechanism in themselves,
regulated by the centripetal fibres of the pulmonary vagi, since
these excite the inspiratory centres when the lungs contract, and*
the expiratory centres when the lungs expand/ In this way, the
inspiratory state of the lungs reflexly cuts off' inspiration and
promotes expiration, and the expiratory state reflexly inhibits
expiration and effects inspiration. Two different kinds of afferent 7
fibres must be distinguished in the pulmonary vagi — those excited .
by the dilated and those excited by the contracted state of the
lungs ; the former are in relation with' the expiratory centres, the
latter with the inspirator/.

The explanation offered by Stefani is somewhat different.

He holds that the inspiratory fibres are stimulated, not by.
pulmonary retraction but by the fall of pressure in the alveoli,
and that the expiratory fibres are excited, not by pulmonary /
expansion, but by rise of pressure in the alveoli. These smallj
modifications explain why in cases of stenosis of the air-passages]^
the breaths are deep and infrequent (dyspnoea), and why in cases
of restriction of the respiratory tract there are frequent and
superficial respirations (tachypnoea). For in the first case, both
inspiratory depression and expiratory rise of intrapulmouary
pressure must be greater, owing to the greater difficulty
encountered by the air in penetrating or leaving the respiratory
passages. In the second series of cases the conditions are
exactly opposite, so that the excitation of both kinds of vagus
fibres is shorter and weaker.

Confirmation for this theory of automatic regulation by the
afferent fibres of the pulmonary vagus has been sought in the
study of the phenomena consequent on exciting the central ends
of the divided vagi. Owing, however, to the presence of the two
antagonistic kinds of fibres in the vagus, the effects of its central
excitation are not constant, but vary with the nature and intensity

462

PHYSIOLOGY

CHAP.

of the stimuli, so that the action now of the inspiratory, now of the
expiratory fibres preponderates.

* As early as 1847 it was remarked by Traube, and later on by,
Eosenthal, that electrical excitation of the central end of a'
vagus cut in the cervical region caused excitation of the inspiratory
centres, as shown by acceleration of rhythm, and with stronger
stimuli by an inspiratory tetanus (Fig. 213). This proves that
the vagus trunk contains centripetal fibres which on excitation
act on the inspiratory centres by acceleration of their rhythmical

Kid. 213. — Inspiratory effects of electrical excitation of central trunk of vagus in rabbit (Fredericq).
The period of excitation is marked on the abscissa. The tracing shows the respiratory
oscillations of pulmonary pressure.

impulses. This result, however, is not constant; it is only
necessary to alter the strength of the exciting current in order to
produce a diametrically opposite effect, i.e. t slowing of rhythm,
with preponderating expirations, and also expiratory tetanus.
This contrary effect proves that the vagus contains other afferent
fibres which act on the expiratory centres. If these are rarely
manifested with electrical excitation of the central end of the

FIG. '214.— Expiratory effects of electrical excitation .of central trunk of vagus in chloralised
rabbit (Fredericq). The period of excitation is marked on the abscissa. Eacli stimulation is
followed by a respiratory arrest.

vagus, it is because the antagonistically working fibres pre-
ponderate. Chemical excitation of the central end of the vagus,
however, causes reflexes of a predominating expiratory nature
(Gad). When the animal is poisoned with strong doses of chloral
hydrate, which, as we have vseen, weakens the activity of the
inspiratory centres, the centripetal expiratory fibres of the vagus
come into play. For under the.se conditions electrical stimulation
of the central end of the vagus nerve is invariably followed by an
expiratory tetanus, as appears from the researches of L. Fredericq
and Wagner (Fig. 214).

xni KESPIKATOKY EHYTHM 463

According to Patrizi and Franchini, the diaphragmatic arrest
on stimulation of the central trunks of the vagus is not invariably
(in profoundly anaesthetised animals) the effect of predominance of
the excitatory muscles, but may be merely an inhibitory suspension.
Whatever the phase in which the diaphragm is overtaken by the
appropriately graduated stimulation of the vagus, it becomes
immobilised without change of tone (level of record), and completes
its movement at the close of the inhibitory respiratory effect,
resuming it from the point at which it had been interrupted.
They do not deny that excitation of the vagus may, at a certain
point, produce respiratory movements, since they more than once
had occasion to verify that particular result ; but they do affirm
that the respiratory arrest on centripetal stimulation of the vagus
is not seldom a merely inhibitory phenomenon.

Treves (1905) also admits that the effects of faradisation of
the central end of the vagus are inhibitory in character. After
eliminating the action of the principal expiratory muscles by
ligature of the cord at a point below the origin of the phrenic
nerve, he found that section of the vagus was followed by more
intense respirations, and sometimes by a prolonged inspiratory
tetanus, interrupted only by passive expirations, which became
more and more frequent, and irregular in their rhythm and ampli-
tude. Under these conditions the excitation of the central end
of the vagus had a constant inhibitory effect, reducing the depth
of the inspiratory act, and the frequency of respiration may
be augmented or diminished according to the more or less pro-
nounced tetanic character of the respiration after section of the
vagus.

VII. Besides the pulmonary fibres of the vagus, other influences
may affect the rhythmical impulses of the bulbar respiratory,
centres. These may emanate from the cerebral centres, or from
the periphery of the centripetal nerves in general, and particularly
of the sensory nerves, with which the mucosa of the nasal,
buccal, pharyngeal, laryngeal and tracheal air-passages are
provided.

The afferent influences from the cerebral centres to the bulbar
centres of respiration are conspicuous after section of the vagi.
The respiratory type, which, as wre have seen (Fig. 211), follows
immediately on this operation, depends on and is specially
maintained by the active intervention of the cerebral centres, in
lieu of the missing regulatory influence of the vagi. To prove
this, it is only necessary to compare the effects of separation of
brain from bulb in animals with intact and with divided vagi.
In the former, as we know, the normal respiratory type is not
greatly modified after a transitory disturbance due to the traumatic
effects of the operation; in the latter, on the contrary, extraordinary
changes in the mode of respiration ensue. The respiratory move-

464 PHYSIOLOGY CHAP.

ments succeed each other with marked retardation; the inspirations
become deeper and are followed by long pauses (inspiratory
tetanus) ; the expirations are rapid, with active intervention of
the abdominal muscles, and are followed by brief pauses ; at the
same time the normal rhythm, i.e. the regular succession of
inspirations and expirations, remains unaltered. These effects
may vary in intensity, and inspiratory tetanus is sometimes
absent, in accordance probably with the varying degree of
operative traumatism and consequent haemorrhage. But in all
cases the amplitude of respiration or pulmonary ventilation in the
unit of time is diminished by about one-half, so that the animal
no long time after succumbs to asphyxia.

These striking results, as disclosed by the researches of
Marckwald in Kronecker's laboratory (1887), and confirmed in
essentials by Loewy in Zuntz' laboratory (1888), show the great
importance assumed by the functions of the centres and afferent
nerve-paths from brain to spinal bulb in pulmonary respiration,
when the vagi, which normally regulate respiratory rhythm, are
cut off. While, however, the afferent vagus tracts to- the bulbar
respiratory centres are able perfectly to compensate the deficit in
the cerebral paths, these last are only partially able to compensate
for the failure of the vagus. The effects of double deficiency show
'that the whole of the other afferent paths to the respiratory centres
which remain intact, after section of the vagi and separation of
the brain from the bulb, are incapable of influencing the said
centres so as to provide the respiratory movements essential for
adequate pulmonary ventilation.

Among these afferent nerve-paths, special mention must be
made of the trigeminus, to which the nasal mucosa owes its
sensibility ; the superior and inferior laryngeal branches of the
vagus, which contain the sensory fibres to the laryngeal and
tracheal mucosa ; and the glosso-pharyngeal, which serves the
specific sensibility of the tongue and pharynx. All these paths
are in special relation with the expiratory centres, and their
stimulation, whether at the peripheral ending or along their
course, almost invariably produces expiratory effects.

We know how readily sneezing is induced by chemical excita-
tion of the nasal mucosa. Its electrical stimulation produces
expiratory arrest (Hering and Kratschmer). Expiratory standstill,
or a true expiratory tetanus, can also be elicited by stimulation of
the endings of the trigeminus, which are distributed to the skin of
the face, if a large surface is excited, e.g. if the animal's head is
dipped into water.

Coughing is produced by the stimulus of foreign bodies upon
the mucosa of the larynx and windpipe, transmitted more
particularly by the afferent paths of the superior and inferior
laryngeals. Gentle electrical stimulation of the superior laryngeal

xin RESPIRATORY RHYTHM 465

produces a retarded respiration, with prolonged expiratory pauses.
With a stronger stimulus the expirations become very vigorous,
and assume the form of expiratory tetanus (Rosenthal).

The effects of stimulating the glosso - pharyngeal are less
constant. Apparently this determines respiratory standstill in
the phase of the respiration that obtained prior to excitation.
Few experiments, however, have been made on this point.

In any case these afferent nerve fibres, situated along the
air-passages, which when stimulated have a moderating action
on the respiratory processes, or a decisively active expiratory
influence, do not function under ordinary conditions of lite, since.
they have normally no tonicity, and are not therefore capable,
like the pulmonary fibres of the vagus, of exerting a constant
influence upon the bulbar centres. Cocainisation of the nasal
mucosa (Marckwald), and bilateral intracranial section of the
trigeminus (Loewy), effect no permanent alteration in respiratory
rhythm. On a rabbit operated on in this way successive vagotomy
produces no more pronounced effect than when the operation is
performed on an intact rabbit. The paths of the trigeminus do
not, therefore, normally exert any regulatory control upon the
respiratory impulses sent out from the centres.

The same may be affirmed of the afferent paths of the glosso-^
pharyngeal and superior and inferior laryngeals, section of which
produces no permanent modification of respiratory rhythm.

All other centripetal paths, which lead directly or indirectly,
from above or from below, to the respiratory centres, and which
under normal conditions do not influence the respiratory mechanism,
may, when artificially excited, or under certain fortuitous conditions,
produce modifications in respiration.

Stimulation of the olfactory nerve by odoriferous substances
may give rise now to inspiratory and now to expiratory effects,
according to the acuteness of the sensations evoked, and their
pleasant or unpleasant character. Electrical excitation of the
optic and auditory nerves regularly produces acceleration of
rhythm, with reinforcement of inspirations. The sensory
nerves to the skin, when slightly stimulated, excite inspiratory
effects ; with painful stimulation, they exaggerate and prolong the
expiratory acts. The phrenic nerves also contain afferent fibres,
which when excited behave like the cutaneous nerves. So, too, the
centripetal nerves of the sympathetic system are able reflexly to
modify respiratory rhythm. According to Pflliger, excitation of
the splanchnic invariably produces respiratory effects, which do not
occur on exciting other rami of the sympathetic.

The majority of these reflexes are of no essential importance
to the theory of the nervous mechanisms that normally and
continuously regulate the respiratory rhythm. On the other
hand, a special importance in the auto-regulation of respirations

VOL. I 2 H

466 PHYSIOLOGY CHAP.

attaches to another group of reflexes, which till now have been
little considered by physiologists, i.e. those reflexes determined by
the impulses which originate in the afferent nerves to the
respiratory muscles.

In speaking of concomitant respiratory movements (p. 421)
we said that in many animals each inspiratory act is accompanied
by active dilatation of' the glottis and nostrils, while constriction
of these apertures accompanies each act of expiration. K. du
Bois - Keyniond and Katzenstein (1901) observed in dogs that
these movements of the glottis may appear also in double pneumo-
thorax, or when the lungs are retracted. Under these conditions
they noted that the passive compression of the thorax (expiratory
position) determined a constriction, while the elastic return to the
inspiratory position determined active dilatation of the glottis.
From this they inferred that these effects depend on changes in
the position of the thorax In all probability this is an example
of co-ordination of reflexes by way of the sensory muscular and
tendinous innervation, which, as we shall see in Vol. III., has been
worked out by Sherrington for locomotor movements. •

The two authors named above have indicated another fact of
great importance to the theory of central respiratory innervation.

/They described the concomitant respiratory movements of the
vocal cords with intact thorax, during the movements of the
diaphragm determined by excitation of the phrenic in the neck.
Under these conditions they saw that the tetanic stimulation of
one or both phrenics determined movements of adduction in the
vocal cords. The contraction of the diaphragm preceded by an
^'appreciable interval the closure of the glottis, which lasted as
long as the stimulation of the phrenic. They interpreted these
reflexes as due to excitation of the pulmonary flbres of the vagus,
which tallies with the auto -regulatory theory of Hering and
Breuer.

Mislawsky (1892) also communicated to the International
Physiological Congress at Turin, a reflex action of quite similar
character, as established by the work of his pupil Luria. Excita-
, tion of the tendinous centre of the diaphragm determines expira-
tory arrest of the thorax. Stimulation of the peripheral trunk of
the phrenic nerve has the same effect. Here, again, as in the
case of E. du Bois - Eeymond and Katzenstein, we have an
inspiratory act (contraction of the diaphragm) determining
reflexly an expiratory act (adduction and closure of the vocal,
cords, expiratory position of thorax). Mislawsky, too, holds that
^ j these reflexes are completed by way of the pulmonary vagi. « As a
matter of fact they disappear after section of the vagi.

Baglioni (1903) in his study of the same reflexes took into
consideration the afferent nerve paths, which, as we have seen, run
in the phrenic nerves along with the afferent fibres.

xiii KESPIKATOKY EHYTHM 467

In order to study the reciprocal and opposite action of the
two respiratory phases (inspiration and expiration) he uses a pro-
longed contraction of the rabbit's diaphragm, produced by direct
faradisation of the diaphragm itself, exposed by means of a large
aperture in the thorax, artificial respiration being temporarily
suspended.

He noted that when the contraction of the diaphragm had
hardly begun the nostrils became fully dilated, as in every normal
act of inspiration. Almost at once, however, if the tetanic con-
traction of the diaphragm was kept up, the nostrils became con-
stricted nearly to complete closure, and remained in that position
during the whole period of the contraction.

On bilateral section of the phrenic in the neck this reflex
disappeared completely. Accordingly it originates in the con-
tracted diaphragm, and determines secondarily the closure of the
nostrils, which, as we have seen above, is a purely expiratory act.
" Hence," concludes Baglioni, " we have here a respiratory reflex of
essentially the same character as those respiratory reflexes on
which Hering and Breuer based their theory of auto-regulation,
but with this difference, that here the afferent impulse travels not
by the pulmonary vagus but by the centripetal fibres of the
phrenic."

Recently (1907) Baglioni has emphasised the importance he
attaches to these respiratory reflexes, which must be determined
by the two respiratory phases, the inspiratory muscles by their
contraction exciting the centres, and thus reflexly determining the
contraction of the expiratory muscles, and vice versa.

VIII. From all that has been said above, we may deduce the
following conclusions, which are of fundamental importance to the
theory of respiratory innervation : —

(a) Normal respiratory rhythm (eupnoecC), which is the best
adapted to produce with minimum expenditure of energy that
degree of pulmonary ventilation which sutiices for the chemical
needs of the organism, is essentially conditioned by the activity of
the centripetal fibres of the pulmonary branches of the vagus,
which are in direct relation with the bulbar centres. It persists
after the separation of the spinal bulb from the brain.

(&) It is the function of the pulmonary fibres of the vagus to
maintain the lungs in that state of average dilatation which
obtains when all the respiratory muscles are inactive. They are
excited on the one hand by the rise of pulmonary pressure and p£
the inspiratory dilatation of the lungs, which reflexly determine
the act of expiration, just as the fall 0f pulmonary pressure and
the expiratory retraction of the lungs reflexly determine the act
of inspiration.

(c) When the auto-regulation of respiration by means of the
vagi is. suppressed, an abnormal type of respiratory rhythm appears,

468 PHYSIOLOGY CHAP.

which, although it provides for a degree of pulmonary ventilation
sufficient to maintain life, must yet be termed dyspnoeic, since it
is not obtained without useless expenditure of muscular energy.
Under these conditions it seems to us probable that a vicarious
self -regulation comes into play, due to the rhythmical and
alternate excitation of the sensory paths to the inspiratory and
expiratory muscles.

(d) The dyspnoeic respiration, consequent on section of the vagi,
is largely maintained by the active intervention of the cerebral
respiratory centres which tend to compensate the deficiency of the
vagus. When, indeed, the influence of the descending cerebral
tracts is also cut off, respiration becomes far more highly
dyspnoeic, and is inadequate for the needs of existence, although
rhythm, i.e. the alternation of inspiratory and expiratory acts, still
persists.

(e) All the other centripetal nerves, which are capable of
reflexly influencing the respiratory mechanism, are normally
inactive, since their occlusion produces no apparent change in
respiration, and they are inadequate, after the vagi a'nd afferent
cerebral paths to the bulb have been cut out, to compensate the
deficiency and substitute their own functions.

It would be a mistake to conclude from these facts as a whole
that the rhythmically alternating impulses which emanate from
the inspiratory and expiratory centres localised in the spinal bulb
are merely reflex acts determined by stimulation of the said
afferent nerve tracts. As a matter of fact, we have seen that
respiratory rhythm, even when the spinal bulb is cut off from the
brain and section of the vagi, persists in a highly energetic form,
although it is inadequate for physiological requirements. If, after
these two operations, we proceed to a third, in which the cervical
cord is bisected at the level of the exit of the fourth pair of
cervical nerves, from which the fibres' of the phrenic emerge, the
thoracic abdominal respiratory rhythm persists, though it is
represented almost exclusively by the energetic rhythmical con-
tractions of the diaphragm (Eosenthal). Lastly, if the spinal bulb
is suddenly and completely isolated by another transverse cut
below the tip of the calamus scriptorius all thoracic movement
ceases, but the facial, nasal, and laryngeal movements that
accompany the movements of respiration continue. That is to
say, the respiratory centres persist in their rhythmical functions,
although these can only find expression in the few motor paths
that remain (Eosenthal), .

Since, however, we know that the sensory tracts whicn are
still connected with the bulb under these conditions of isolation
are able reflexly to provoke rhythmic and alternate excitation, it
would be rash to conclude from these data that the respiratory
rhythm of the bulbar centres is automatic in character, i.e. entirely

xin RESPIRATORY RHYTHM 469

independent of external stimuli. It is also legitimate to suspect
that the rhythmical activity of the isolated bulb may be main-
tained by irritation from, the sections and the external agents
acting on the surface of these sections. We must now turn to a
striking series of facts which show that the rhythmical activity of
the respiratory centres is influenced in great measure, besides the
afferent stimuli by the nerve paths, by the condition of the blood
and lymph that are circulating in them, i.e. by the nature of the
medium which bathes the nervous elements of which they are
constituted.

IX. Under all the varied circumstances, natural or experi-
mental, in which there is an abnormal rise of venosity of the
blood in consequence of the diminished gaseous exchanges between
the environment and the organism, dyspnoea is produced, i.e.
increased intensity and frequency of the respiratory rhythm.
This occurs regularly :

(a) When the animal (or man) is forced to breathe an atmo-
sphere surcharged with carbonic acid ;

(&) Or an atmosphere poor in oxygen and rich in indifferent

(c) When under any morbid conditions (pneumonia, pleuritic
effusions, pneumothorax) the alveolar respiratory surface is
abnormally diminished ;

(d) When owing to uncompensated organic lesions of the heart
there is an abnormal retardation of circulation ;

(e) When, lastly, owing to profuse haemorrhage, or copious
bleeding, the mass of blood in circulation is largely diminished.

Since the respiratory movements are destined by the ventila-
tion of the lung to provide for the normal gas exchanges between
the atmosphere and the blood, and indirectly between the blood
and the tissues, these facts show that the amplitude of the
respiratory movements, i.e. the degree of pulmonary ventilation,
increases with the need for increased elimination of C02 and 0.,
absorption. Accordingly, there is a certain degree of adaptation
between the gas exchanges and the respiratory activity, which
implies that either the carbonic acid, or other waste products of
the tissues avid of oxygen, act as direct stimuli to the respiratory
centres, or at least modify their metabolism so as to increase their
rhythmical and alternate function.

The theory of adaptation between the need for air and the
respiratory magnitude of ventilation is confirmed by the fact that
there is exaggerated activity of the respiratory centres, and there-
fore of the depth and frequency of respiration, whenever the
organic processes of combustion, i.e. the consumption of oxygen
and production of carbonic acid, are increased. The most classical
example of this fact is, under normal conditions, the dyspnoea
developed in consequence of intense muscular work. The influence

470 PHYSIOLOGY CHAP.

exercised by work upon the respiration of the muscular tissues
and the combustion which takes place within them is enormous.
To form an idea of it we must consider the variations per tiin6
unit of the quantity of carbonic acid given off in different states
of the muscle. According to Gad, the same individual gave off in
one minute from the lungs : —

During sleep 0'38 grms. of C02

During the waking state and horizontal position . 0*57 „

In walking 1-42 „

In more rapid walking 2O3 „

In climbing 3'83 „

It will be noted that in the work of climbing ten times
as much carbonic acid is eliminated as in sleep. The need
of breathing, therefore, increases proportionately, and is amply
•satisfied by the dyspnoea which provides for the due elimination of
the excess C02 formed, and absorption of the excess 02 consumed.

Analysis of the blood gases of animals which are dyspnoeic in
consequence of muscular work show, however, that boj/h carbonic
acid and oxygen are present there in normal quantities. Accord-
ing to the elegant researches of Geppert and Zimtz (1888), the
oxygen is somewhat increased and the carbonic acid considerably
diminished below the normal. There is thus a certain adaptation
between the need of air and the pulmonary ventilation, but it is
not strictly commensurate with the chemical requirements of our
tissues. The dyspnoea of muscular work exceeds the limit of strict
necessity, i.e. there is a superfluous increase of the respiratory
activity which cannot be explained either by the increase of C02,
or by the diminution of 02 in the blood. Since the effect of
energetic muscular work is to diminish the alkalinity of the blood,
it has been supposed (in order to account for the increased activity
of the respiratory centres) that the muscles during their activity
develop an acid product of consumption, different from carbonic
acid, which is capable of exciting the respiratory centres (Curt
Seehman). It is possible that this product may be lactic acid,
which is developed and poured out into the blood by the muscles
during their activity (Spiro), and which is found, e.g., in the urine
of soldiers after a long and fatiguing march, or gymnastic
exercises (Colasanti).

But in explaining the superfluous increase of respiratory
activity in the dyspnoea of muscular fatigue, we must also take
into consideration the increased temperature of the blood, which
is necessarily associated with the increased combustion of the
muscular tissues, and which in itself is capable of provoking a
dyspnoeic acceleration of respiratory rhythm to which the name of
tachypnoea, polypnoea, or thermal dyspnoea, characterised by very
rapid and superficial respirations, with increased tone of the
inspiratory centres, has been given.

xin EESPIEATOEY KHYTHM 471

The simplest case of tachypnoea occurs in dogs, under perfectly
normal conditions, during the hottest days of summer. The
accelerated rhythm, which causes an abundant evaporation of
water, is, in this case, a protection against an abnormal rise in
temperature of the blood, rather than against the accumulation of
carbonic acid there (Bichet). The thermal excitation of the
cutaneous nerves is probably in this case the sole condition acting
reflexly upon the bulbar centres, so as to determine tachypnoea
(Gad).

Under all other contingencies in which there is already an
abnormal rise in the temperature of the blood, as in fever due to
any cause, the phenomenon of dyspnoea is much more complex ; but
one of the fundamental conditions that determines it is certainly
the abnormal rise of excitability in the centres, due to the
heightened temperature of the blood that circulates in them.
Goldstein demonstrated this in 1872 in Fick's laboratory. In
order to avoid rise of general temperature in the animal, he
surrounded the carotids with two little metal sheaths, with double
walls, within which he circulated water warmed so as to produce
febrile temperature in the pharynx, while the rectal temperature
remained steady. There was at once a rhythmical acceleration of
respiration (tachypnoea) in the animal, due solely to the heating of
the blood circulating in the head, which raised the excitability of
the bulbar centres (particularly of the inspiratory centres). In
fact, under these conditions it was found impossible to produce
apnoea (which we shall discuss elsewhere) with artificial
respiration.

In face of these facts it seems indubitable that the pulmonary
ventilation, determined by the dyspnoea due to muscular fatigue,
which is excessive as regards the chemical needs of the tissues,
may and should be explained, at least partly, as an effect of the
increased excitability of the bulb, consequent on increased tempera-
ture of the blood. The genesis of febrile dyspnoea is highly
similar.

Jappelli has recently (1906), from his experiments on man and
other animals (dog, rabbit, pigeon), demonstrated a fact which
tends to explain many forms of polypnoea in muscular work
(running, jumping, etc.) in a different way to those heretofore
considered, i.e. independent of the chemical or thermal changes in
the blood which irrigates the respiratory centres. He saw that
there is in the respiratory nerve centre a distinct tendency to
synchronise its rhythmical and alternate impulses with the
external rhythmical impulses, which .are eventually transmitted to
the central nervous system via the sensory nerves. If, e.g., in a dog
breathing normally, the central end of the sciatic is rhythmically
excited with weak induced currents of varying frequency (40-80
per minute), it will be seen after a longer or shorter latent period

472 PHYSIOLOGY CHAP.

that the respiratory rhythm is modified, becoming more frequent
and perfectly synchronous with the rhythm of the artificial stimuli.
Again, the polypnoea induced in man by rhythmical exercises which
impart considerable vertical oscillations to the torso (running,
jumping), is characterised by a tendency to synchronisation
between the respiratory phases and the rhythm of rise or fall of
the centre of gravity. These rhythmical movements of running
or jumping must, therefore, determine afferent nerve impulses to
whose rhythm the respiratory centre tends to adjust the rhythm
of its own proper activity. And since the rhythm of the afferent
nerve impulses is in these cases more frequent than the rhythm of
normal respiration, dyspnoea ensues as the direct effect.

This theory also explains certain peculiarities of the said
dyspnoea; for example, the fact of its rapid onset, at the very
beginning of the running and jumping, i.e. before it is possible to
assume any production of toxic substances or rise of tempera-
ture, such as are invoked in the preceding theories. So, too,
its immediate disappearance, sometimes at the very moment
the exercise is over. On this theory, again, it is easy to explain
the other fact known to professional athletes, to wit, that properly
trained runners are able to hold out for a long time without
experiencing dyspnoea.

" We can also understand " (adds Jappelli) " what the import-
ance of learning how to take breath in running may be. How, if
this were determined by the quantity of blood circulating in
the capillary network of the bulb (deficit of 02, increase of C02),
could it be modified by a physical education ? The polypnoea
of running is, however, mainly a luxus-respiration, an effect of
synchronisation, which represents a useless expenditure of energy,
and which, once the exigencies of the respiratory exchanges are
satisfied, may be modified for the sake of avoiding fatigue. The
education of respiratory rhythm in a runner therefore amounts to
developing in him an inhibitory cerebral faculty, so that he
moderates the frequency of his respiration, opposing the tendency
towards synchronisation with the movements of the lower limbs."

X. Let us now examine whether in normal quiet respiration
(eupnoea) the respiratory activity is commensurate with the
quantity of oxygen required by the tissues, and the carbonic acid
which they exhale ; or if in this case also, as in the dyspnoea of
muscular work, the renewal of pulmonary air is in excess of what
is required, the nervous mechanisms of the respiratory rhythm
being to a certain extent independent of the gaseous content of
the blood circulating in them.

Kosenthal in 1862 espoused the first theory on the strength of
a number of experiments, more particularly the phenomenon of
experimental apnoea, of which he may be termed the discoverer,
and which we shall consider below. His theory, broadly speaking,

xin KESPIKATORY EHYTHM 473

found general acceptance, and Pflliger gave it the authority of his
name in 1868.

A. Mosso was the first who, in 1885, pointed to some quite
evident facts which, according to him, show that " the number and
extent of the respiratory movements are not always in close relation
with the respiration of the tissues and the blood, while they are
directly proportional with the need for supply of oxygen or
elimination of carbonic acid." He gave the name of extra- or
luxus-respiration to the excess renewal of air in the lungs, such
as normally occurs and is not, strictly speaking, necessary to the
organism.

Some of the facts which he brings forward do not really
appear to stand in close relation with the theory of luxus-
consumption. Such, e.g., are the well- known fact that respira-
tion is profoundly modified by simple nervous activity (emotions,
intellectual work) quite independent of the degree of venosity
of the blood; that dogs after running frequently pass from
deep respiration (dyspnoea) to quick and superficial breathing
(tachypnoea) as if the register were suddenly changed without
apparent reason ; again, that in sleep, both in man and other
animals, temporary disturbances of a purely nervous character
may be observed in the regularity of the rhythm. All these
effects confirm what we said above as to the influence exerted by
the nervous system upon the regulation, and more particularly
the mode of distribution of the work of the respiratory muscles,
and have nothing to do with the capacity for pulmonary ventila-
tion, which may continue practically unchanged in the time-unit
under very dissimilar and even opposite forms of respiratory
rhythm (Kosenthal).

Another fact brought forward by Mosso is more significant,
i.e. that we can voluntarily reduce to about one-half the amount
of air inspired, without inconvenience, for a considerable period
(10-15 minutes). At the same time this would only bear on the
theory of luxus-respiration, if it could be proved that breathing,
when voluntarily restrained for so long a time, would not be
followed by a compensatory dyspnoea.

Lastly, we attach great importance to the observations made
by Mosso during his Alpine excursions, which show that at a level
of 3000 metres much less air is breathed . than at sea-level :
hence at sea-level the amount of air respired far exceeds the needs
of the organism. In proportion as one ascends, the superfluous or
luxus-respiration diminishes owing to the rarefaction of the air.
These high altitude effects do not, however, appear to be constant,
which as we shall see impairs their cogency for luxus-respiration
in the plains.

According to Mosso, luxus-respiration (which we may shortly
designate eupnoea) is profitable to the organism, because it makes

474 PHYSIOLOGY CHAP.

the regulating factors less complex. It is clear that if the
ordinary respiratory mechanism were not, within certain limits,
independent of the chemical needs of the body, or the gas content^
of the blood, then " at every change of the barometer (some of
which are enormous) every man and every animal would have
suddenly to alter both frequency and depth of respiration, in order
to equalise the changes in the atmosphere " (Mosso, 1898).

Here, however, we touch upon new problems, which demand
solution. For if we accept this theory of eupnoea, it may be
asked : " What are the external factors causing this excess of
pulmonary ventilation ? If in the dyspnoea from hard muscular
work, pulmonary ventilation increases to oppose the increased
venosity of the blood, and if this effect exceeds the immediate
requirement, must not the same effect occur in eupnoea, and the
venosity of the blood diminish to such an extent that it would in
a short time become inadequate to maintain the activity of the
centres ? If, in order to explain the dyspnoea of work, we are
obliged to invoke the presence of a (probably acid) waste product of
muscle in the blood, capable of sur-exciting the respiratory centres,
are we not equally obliged to admit that an analogous product
may be acting in eupnoea, stimulating the activity of the centres,
and raising the respiratory capacity (by about one-half) beyond
the immediate need ?

Again, how does the chemistry of respiration alter at high
altitudes where luxus-respiration ceases ?

According to the analyses of blood gases made on the dog by
Friinkel and Geppert (1833) to test the effect of varying baro-
metric pressures, in air rarefied to a pressure of 410 mm. the 02 and
(J02 content of arterial blood is not perceptibly altered ; and at a
pressure of 198 mm. the loss of gases from the blood is still extremely
small (1 part 0.2 and T65 part C02). Mosso attributes great
importance to this relatively minute diminution of the C02 of the
blood. He believes it to represent a state of the blood contrary to
that which prevails in asphyxia, and proposes to call it acapnia,
holding it to be one of the causes of mountain sickness. This
conclusion seems to us to be premature and hazardous. We admit
that acapnia, or the abnormal diminution of C0.7 in the blood, can
only be regarded as the effect of two opposite processes, either, i.e.,
of a diminished production of C09, as in sleep, or of its augmented
excretion, as in artificial or forced voluntary respiration. Now
neither the one nor the other condition of acapnia is fulfilled
in respiration at a high altitude above sea-level. From the
experiments undertaken by Mosso upon three soldiers, after they
had rested, so as to exclude the effects of muscular fatigue, it
appeared that " no important modification in the elimination of
CO2 and the volume of respired air can be detected at high
altitudes." This proves that even in rarefied air " the organism

xiii EESPIEATOEY EHYTHM 475

requires its normal supply of oxygen," i.e. it consumes the same
amount, and therefore eliminates the same quantity of carbonic
acid. It may be noted in passing that these facts contradict
the preceding data on which Mosso rests his theory of luxus-
respiration.

Eecently (1906) Zuntz, Loewy, F. Miiller, and Caspari, in the
course of their numerous researches on the physiological action
of climate at high altitudes and of alpine excursions on man,
have enumerated a series of observations and data which directly
contradict the theory of acapnia. They found, as a matter of fact,
that there is in the majority of cases a progressive diminution
of C02 tension in the lungs in proportion with the altitude. Thus,
e.g., while the tension of the pulmonary C09 was in Zuntz, at a
barometric pressure of 715 mm., 38*5 mm., at a barometric
pressure of 689'9 mm. it fell to 32'6, becoming 27'2 at 439'3 mm.
barometric pressure. It is, however, true that there is a
simultaneous increase of respiratory intensity, i.e. an augmentation
of pulmonary ventilation.

The diminished pulmonary tension of the C0.2 would thus be a
secondary effect of increased ventilation, which in its turn depends
upon the diminution of the oxygen in the respired air.

They further note that not every individual presents the same
diminution of COQ tension in respect of altitude. In one person,
e.g., no diminution in C02 tension was noted, and yet he was one
of those who suffered most from mountain sickness. Others, on
the contrary, who exhibited the said diminution, were exempt
from sickness.

In order, at least to some extent, to clear up this uncer-
tainty as tro the theory of eupnoea, and the better to define the
nature of the relations existing between the chemistry and the
mechanics of respiration, i.e. between the gas content of the blood
and the capacity of pulmonary ventilation, it will be well diligently
to examine the various conditions under which it is possible to
observe the phenomenon of apnoea.

XI. If the rhythmic and alternate activity of the respiratory
centres is strictly bound up with the quantity of oxygen and
carbonic acid of the blood that is circulating through them, it
should be suspended when the venosity of the blood is artificially
reduced, so as to render pulmonary ventilation useless. The name
of apnoea has been given to such suspension of the respiratory
movements when they have become temporarily superfluous.

Hook (1667) (see p. 371) was the first to observe it, but he
formulated no conclusion as regards the process by which the
respiratory centres enter into rhythmic activity. The first to
study apnoea by making it the basis of the doctrine of respiratory
rhythm was, as we have stated, Eosenthal (1862). His work was
taken up and enlarged by Pfliiger (1868).

476 PHYSIOLOGY CHAP.

We have seen that when artificial respiration with the bellows
is performed on any animal, the lungs being rhythmically dilated
in proportion as the normal limits are transcended, the animal,
owing to the auto-regulation set up by the vagus, reacts to each
insufflation by a respiratory movement. After a few insufflations,
however, these reactions diminish, and soon cease altogether. If
artificial respiration is now suspended, the animal remains for a
few seconds, half a minute at the outside, without breathing, it
has become apnoeic. To Rosen thai this phenomenon of apnoea
appeared to be an experiment-urn crucis in favour of the doctrine
which subordinates the respiratory movements to the degree of
venosity of the blood. When there is a relative augmentation of
C02, and a relative diminution of O2, there is in the time unit
a corresponding augmentation in the respiratory capacity. The
latter then depends upon, and is in strict ratio with, the venosity
of the blood. The vagi, according to Eosenthal, only distribute
the work of the respiratory muscles in various ways, since it
remains approximately the same after section of these nerves.

But the forced apnoea of artificial respiration is by no means
so simple a phenomenon as was assumed by Rosenthal ; indeed
it is highly complex. It can be easily demonstrated that it
depends not so much on the diminished venosity of the blood, as
on an inhibition or reflex paralysis of the rhythmical activity of
the centres, determined by mechanical excitation of the centripetal
pulmonary branches of the vagi. Brown -Sequard (1877) was the
first who brought forward this opinion, founding it on the fact
(subsequently confirmed by all experimenters) that apnoea is
entirely absent or lasts for a few seconds only, when forced
respiration is employed after section of the vagi. It is therefore
conditional on the integrity of those nerves.

On the other hand, there are not wanting facts which show
that the diminished venosity of the blood is of secondary importance
in determining apnoea. In 1865 Thiry noticed that he was able to
produce apnoea even when air mixed with half its bulk of some
indifferent gas, such as hydrogen, was insufflated. It was sub-
sequently found by Fredericq, Gad, and Knoll that in order to
produce apnoea, it is not necessary to insufflate with pure air, but
that provided the vagi are intact, repeated insufflation with the
same air (which becomes more and more charged with carbonic acid
and poorer and poorer in oxygen) suffices to produce the phenomenon.
Knoll further observed that after prolonged pulmonary ventilation,
the apnoeic state is persistent even when the blood becomes blackish,
i.e., has assumed the character of asphyxial blood. On exposing
the heart in a rabbit, by removal of the sternum, without opening
the pleura (which is possible in this animal owing to the persist-
ence and bulk of the thymus) and inducing apnoea by energetic
artificial respiration, Gad observed that the right auricle preserves

xiii KESPIEATOEY EHYTHM 477

the usual venous colour, while the left auricle is at first of a bright
arterial scarlet, and then grows darker during the course of the
apnoea, a process which usually ceases only when the colour of the
left auricle has become much darker than the normal. This shows
that the mechanical action of artificial respiration with the bellows
causes by means of the vagi a diminution of excitability in the
respiratory centres. In fact a highly venous blood, which under
normal conditions would determine a rise of excitability in the
rhythmical activity of the centres, is unable, after vigorous artificial
respiration, to interrupt the apnoea.

From these facts as a whole we may conclude that the apnoea
obtained with artificial respiration is the result of a certain ratio
between the venosity of the blood and the excitability of the
respiratory centres. Since it is thus possible to obtain apnoea even
when the venosity of the blood, far from being reduced, has
exceeded the normal limits : since, on the other hand, it does not
appear after section of the vagi, i.e., when the moderating influence
exerted by these nerves upon the excitability of the bulbar centres
when mechanically stimulated, is eliminated, — it follows that the
said apnoea must depend principally upon the reduced excitability
of the respiratory centres.

Miescher proposes to give the name of true apnoea to that which
is determined by the diminished venosity of the blood, and spurious
apnoea to that which depends on the diminished excitability of the
respiratory centres. Before accepting" this distinction, we must
inquire whether there is any true apnoea in Miescher's sense, and
whether it is possible to produce it artificially in man or other
animals.

XII. Let us in the first place consider the phenomenon of
foetal apnoea. We know that under normal conditions, so long as it
is contained within the uterus, the foetus performs no respiratory
movements ; it is apnoeic. The placental circulation provides for
the exchange of gases necessary to the internal respiration of the
foetal tissues. The umbilical arteries conduct the blood that has
become venous in these tissues to the placenta, and the umbilical
veins reconduct the blood which has become arterial by gas
exchanges with the maternal blood, to the foetus. The trans-
formation of arterial into venous blood is, however, but little
accentuated in the foetus. According to Zweifel and Zuntz, the
colour of the blood in the umbilical arteries differs little from that
of the umbilical veins, showing that the foetus consumes little
oxygen, and gives off little carbonic acid. Enclosed within the
maternal womb, immersed in a tepid bath, it has no need to
provide for its own calorification ; the muscles and digestive
glands are in almost complete repose ; the heart is the only
foetal organ that functions with any activity, and consumes a
certain amount of energy (Pfliiger). At the seventh month the

478 PHYSIOLOGY CHAP.

foetus is perfectly vitalised, so that its respiratory apparatus is
even at that time fully developed and ready to function. If, then,
during the last two months of pregnancy no respiratory acts ar»3
performed under normal conditions, we may say that it is in a
state of apnoea, because having every aptitude for breathing, it
does not breathe.

At the end of 1858 Schwarz enunciated the doctrine that
foetal apnoea depends on the fact of the apnoeicity of foetal blood
in relation to the low excitability of the respiratory centres. The
foetus does not breathe, because the physiological cravings of
its tissues are amply provided for by the utero-placental gas
exchanges, but we must also admit that the excitability of its
respiratory centres is lower than in those of the mother, the
activity of which is maintained by blood of the same degree of
venosity as that which circulates in the foetus.

The first respiratory act of the foetus is accomplished when any
cause whatsoever compresses the vessels of the umbilical cord, or
impedes access of the maternal arterial blood by the placenta.
This may occur even within the uterus, as Vesalius pointed out in
1542. Under these conditions, if the interruption to the gas
exchange persists, the foetus may perish, asphyxiated within the
uterus. But if the venosity of the foetal blood develops slowly,
as when the mother is slowly dying, the foetal respiratory centres
gradually lose their excitability before ever they have become active.

Under normal conditions the foetus begins to breathe when in
consequence of the expulsory act of parturition or detachment
from the placenta, the venosity of the foetal blood increases so
rapidly as to dispel the torpor of the respiratory centres. In
many cases, however, when by long travail the excitability of the
respiratory centres has become abnormally weakened, the high
venosity of the blood is not sufficient in itself to provoke the first
acts of respiration (asphyxial foetus). In such cases it is necessary
to start respiratory activity by employing accessory stimuli,
mechanical, thermal, or electrical (cold air, cold bath, slaps, elec-
trical shocks).

Under conditions of normal excitability of the foetal respiratory
centres, the rapid increase of venosity in the blood suffices to cut
short the iutra-uterine apnoea at the moment of birth, as is
demonstrated by numerous authentic observations upon foetuses
that are still wrapt in their integuments, and sufficiently protected
from the cold of the air, and which yet begin to breathe at the
simple interruption of the placeutal circulation, or ligature of the
umbilical cord. It is easy to repeat this demonstration on the
foetuses of rabbits or guinea-pigs (Engstrorn). In the foetuses of
dogs taken from the uterus with the integuments intact, respiration,
on the contrary, does not begin regularly until the integuments
are lacerated (Pfluger). In this case, then, besides the interruption

xin EESPIRATOEY RHYTHM 479

of the placental circulation, the action of the external air is
required to start pulmonary respiration.

No one can miss the analogy between foetal apnoea and that
which can be provoked on adult animals by artificial respiration
with the bellows. Both the one and the other are due to a certain
relation between the venosity of the blood and the excitability of
the respiratory centres ; neither the one nor the other depends upon
an absolute reduction in the venosity of the blood, but rather upon
the low excitability of the respiratory centres.

Under all circumstances in which there is an abnormal
diminution in the excitability of the respiratory centres, or where
such conditions are produced experimentally, it is easy to obtain a
longer or shorter period of apnoea, by circulating through the
respiratory centres a blood that under ordinary conditions is
adequate for the maintenance of respiratory rhythm.

In the rabbit, ligature of the two vertebral arteries and of one
carotid produces no conspicuous change in the respiratory
mechanism. But if the second carotid is compressed, with arrest
of the cerebral circulation, there will at once be a marked dyspnoea,
followed by epileptiform convulsions,and then by a pronounced delay
in the respiratory rhythm, owing to the exhaustion of the centres
(Kussniaul and Tenner). If free course be then given to the flow
of blood through the carotid, there will instantly be a period of
apnoea, due to the fact that the stimulation of the centres by the
venosity of the blood diminishes rapidly, while their excitability
is slowly re-established (Gad).

A similar explanation holds good for the apnoea produced
immediately after transfusion of blood (or even of a simple
isotonic solution of sodium chloride) in an animal which had
previously been bled copiously, so as to produce asphyxial dyspnoea,
and successive debilitation and retardation of respiratory move-
ments, owing to exhaustion of bulbar excitability (Gad).

Similar to this is the apnoea from vigorous stimulation of one
peripheral trunk of the vagus, which determines a prolonged
suspension of the beats of the heart. During this inhibition of
the cardiac systole arterial pressure falls enormously (as we have
seen), in consequence of which there is a marked diminution in
the arterial afflux to the vessels that irrigate the bulbar respiratory
centres. This determines so pronounced a dyspnoea as, on the one
hand, to subtract all the CO2 from the blood in the pulmonary
vessels, and on the other, to produce a certain degree of fatigue in
the said centres. When the cardiac beats are re-established and
the pulmonary blood, strongly arterialised, flows on to irrigate the
brain, a characteristic suspension of the respiratory rhythm ensues,
because the blood is apnoeic in relation to the somewhat depressed
excitability of the centres (Meyer). Neither, then, is this any " true
apnoea" in Miescher's sense (due, i.e., to the positively apnoeic

480 PHYSIOLOGY CHAP.

character of the blood), even if we allow that the diminished
excitability of the bulbar centres is not the main determinant of
the phenomenon.

XIII. Voluntary apnoea, i.e. the temporary suspension of
respiratory rhythm that we can produce upon ourselves by a
voluntary effort, is a phenomenon entirely different from the cases
of apnoea which we have been examining. It depends upon a
voluntary inhibition of the rhythmical activity of the bulbar
respiratory centres, transmitted by the descending patns from the
so-called motor zones of the cerebral cortex. When the voluntary
suspension of respiration is preceded by a certain number of
profound or dyspnoeic respirations it may last for a very considerable
time. Neither in the one case nor the other, however, is the
duration of this voluntary apnoea in ratio with the vital capacity
of the lungs, nor with the anaemic or plethoric habit, nor with
the body- weight and mass of the tissues in the individual
experimented on (Mosso). We may therefore conclude that the
resistance to asphyxia is a phenomenon essentially connected with
the individual degree of excitability of the nerve centres, and is to
a certain point independent of the composition of the blood, or the
sum of the stimuli acting ab extrinseco on these centres.

In order to form a clear notion of the main objective differences
between voluntary apnoea and the apnoea of artificial respiration,
we need only compare the tracings which show how respiratory
rhythm is picked up in the one case and in the other at the close
of the apnoeic period.

The tracings of Fig. 215 are reproduced from a series of
researches which we made at Bologna in 1874 : they represent
the mode in which experimental apnoea in dogs and rabbits
ceases before and after section of the vagi. They show that
with intact vagi the respirations do not immediately resume
their normal type when the period of apnoea is over, but return
by a slow increase in both inspiratory and expiratory excursions.
After section of the vagi, when the pulmonary ventilation has
been sufficiently prolonged, it is not possible to produce an apnoea
lasting more than a few seconds ; but the resumption of respiratory
rhythm only differs from the preceding by a more rapid increase,
so that the animal more promptly resumes its ordinary rhythm.

We do not yet know how far the increment consequent on
experimental apnoea depends upon the growing venosity of the
blood, and progressive restoration of excitability in the bulbar
centres. But it is easy to show that now one and now the other
condition predominates.

It is a fact that the venosity of the blood is diminished during
apnoea, not so much in consequence of increased oxygen, as because
the carbonic acid which it contains is diminished (P. Bering).
On comparing the quantity of gases extracted from the same

XIII

KESPIKATOKY EHYTHM

481

animal before and during experimental apnoea, Ewald found that

the 02 content of the arterial blood was hardly increased ( + 0*1,

+ 0'9 per cent) while that of the venous blood was considerably

reduced; hence after apnoea the blood, as a whole, is poorer in

FIG. 215. —Increase of respirations after cessation of the apnoea produced with artificial respiration,
before and after section of vagi, in rabbit and dog. (Luciani.) A, A', Adult rabbit, tracheo-
tomised and given artificial respiration with the bellows ; A, respiratory tracing consequent
on apnoea, the trachea being connected with a receiver of 12 litres air, which in its turn com-
municates with a Marey's writing tambour ; A', the same, after section of both vagi.
B and B', Puppies of 3-800 kgrms. anaesthetised with 2 c.c. laudanum injected into a vein,
tracheotomy and artificial respiration with bellows ; B, respiratory tracing after apnoea, the
trachea being joined to a receiver of 30 litres air, communicating with a writing tambour ;
B', the same, after cutting second left vagus.

oxygen. On the other hand, the C02 of the arterial blood
diminished by more than half, while that of the venous blood
increased. This fact is readily explained on the assumption
that forced pulmonary respiration, by compressing the alveolar
VOL. i 2 i

482 PHYSIOLOGY CHAP.

capillaries, moderates the circulation in the lungs, thus lessening
the work of the heart, and lowering the pressure of the aortic
system. The blood in the systemic circulation, during ventilation
with the bellows, remains longer in contact with the tissues, so
that it loses more oxygen and gains more carbonic acid ; in the
lesser circulation, on the contrary, it remains longer in contact
with the pulmonary air, so that it gains a little more oxygen and
loses much more carbonic acid. When the forced respiration
ceases a blood much less venous than usual flows to the brain,
which partly determines the apnoea and gradual establishment of
respiratory rhythm, in proportion as the blood circulating in the
bulb regains its normal degree of venosity.

On the other hand, it is clear that the mechanical stimulation
of the pulmonary ending of the vagi by forced ventilation, which
is capable of depressing the rhythmic excitability of the bulbar
respiratory centres to a very marked extent, must also contribute to
the production of apnoea and the succeeding increase in respiratory
rhythm. In fact, under the influence of the vagi, the apnoea is cut
short and practically disappears, while the successive -increment in
rhythm occurs more rapidly. These effects gauge the influence
exerted on the rhythmical functions of the centres by the
diminished venosity of the blood, when their excitability is not
altered in any way by the mechanical action of forced ventilation.

If we contrast these analyses of experimental with that of
voluntary apnoea it is at once evident that the two phenomena are
the effects of entirely different processes. Fig. 216 shows that
voluntary apnoea, when not preceded by a voluntary dyspnoea, is
followed, not by increase, but by diminution in the inspiratory
and expiratory excursions, i.e. by a brief compensatory dyspnoea,
which ceases when the venosity of the blood (which has increased
progressively during the suspension of respiration) returns little
by little to the normal state on the resumption of rhythmical
activity.

When, on the contrary, the voluntary suspension of breathing
is preceded (as in Fig. 217) by four forced inspirations, the period
of apnoea is longer, and is also followed by a diminution, though less
pronounced than the preceding. This confirms the statement that
exaggerated ventilation diminishes the venosity of the blood, and
depresses the excitability of the centres, through the vagi. If under
these circumstances the apnoea is not succeeded by an increment
this is because the resumption of respiration is retarded by the
action of the will, which inhibits the rhythmical activity of the
bulbar respiratory centres, via the descending paths from the
brain.

Neander (1902) carried out upon himself a number of researches
on the respiratory pause consequent on deep voluntary inspirations.
He differed from Mosso in not prolonging the apnoeic period to the

xiii EESPIEATOKY EHYTHM 483

utmost by means of voluntary inhibition. On the contrary, he
tried as far as possible to eliminate this factor, turning his
attention away from the respiratory acts, so that they should be as
independent as possible of mental influences.

The results of his researches differ from those above described,
inasmuch as the apnoeic period is followed not by a measure of
compensatory dyspnoea, but by the opposite phenomenon, i.e. an
increment in the inspirations similar to that exhibited by an animal
after the apnoea from artificial respiration with the bellows.

' FIG. 216. — Compensatory dyspnoea, consequent on period of voluntary apnoea in man. (Mosso.)
Tracing recorded with Marey's pneumograph.

From his observations, as ?i whole, Meander draws the con-
clusion that the apnoea which he studied must be looked upon as a
combination of true and spurious apnoea. He found, in fact, that
its duration is in ratio with the percentage quantity of the oxygen
of the expired air. On the other hand, it starts as a spurious
apnoea deriving from fatigue of the centres, since a deep inspiration

FIG. 217. — Voluntary apnoea in man, preceded by four forced inspirations, and followed by a
scarcely visible decrement. (Mosso.)

of pure hydrogen equally determines a marked pause, although of
brief duration. The prolongation of the pause consequent on a
series of deep inspirations must be considered as the effect of
greater central fatigue combined with diminished venosity of the
blood, which becomes normal again during the increment of the
succeeding respirations.

XIV. Let us see if it is possible to obtain a true apnoea in
Miescher's sense by substituting gentle continuous ventilation of
the lungs for forced rhythmical ventilation, in order as far as
possible to avoid the mechanical excitation of the pulmonary

484 PHYSIOLOGY CHAP.

vagus endings. This is easy in birds, whose lungs, as we know,
communicate via the bronchi both with the bony chambers, and
with the diaphragmatic, axillary, and abdominal air-sacs. These
last are highly developed ; on opening the body they are conspicuous,
and when they are pierced, and the walls of the abdomen held1
apart by a blepharostat, the air from a gasometer, blown through
the trachea (under a gentle, regular, and continuous pressure),
escapes by the ventral opening.

Bieletzsky (1881) was the first to attempt this experiment.

FIG. 218. — Gradual transition from normal respiration to apnoea, with continuous pulmonary
ventilation in turkey. (Luciani and Bordoni.) Ventilation commences at V at a pressure of
1 mm. Hg. Tracing recorded with a tambour with exploring lever .applied to sternum, con-
nected with a tambour with writing lever.

He stated that he obtained perfect apnoea lasting for the whole
time of the inflation. But he made very few experiments; and
worse, he stopped half-way, omitting the most important part of
the research, i.e. that of seeing what effect was produced by
continuous inflation after the section of the vagi at the neck.

We resumed these experiments with Bordoni at Florence
(1888). The following are the most striking of our results, the
full value of which, in regard to a general theory of respiratory

Fio. 219.— Continuation of previous tracing during prolonged period of apnoea. At point C
ventilation ceases, and there is a gradual return to normal respiration.

rhythm, can be appreciated now that we have made a physio-
logical analysis of the various forms of apnoea.

(a) In turkeys, continuous ventilation with intact vagi
constantly produces the apnoeic state. When air is insufflated
with Waldenburg's gasometric apparatus, at a pressure of 4-5 mm.
Hg, apnoea is instantaneously produced ; at a pressure of 2-3 mm.
Hg the transition from normal respiration to apnoea occurs, with
a distinct decrease in the respiratory acts, which is of brief
duration; finally, at a pressure of 1-1/5 mm. Hg the decrease
previous to apnoea is very gradual and prolonged (Fig. 218). The

XIII

BESPIKATOEY EHYTHM

485

return to normal respiration at the close of insufflation is
invariably preceded by an increase in the respiratory movements
(Fig. 219).

(b) In pigeons also the apnoea is constant. At a pressure of
1-2 mm. Hg expiratory arrest is instantaneous (Fig. 220, A), at
other times it is preceded by a gradual decrease (Fig. 220, B).
The return to normal respiration is also preceded by an increase,
as in the turkey (Fig. 221).

Fia. 220. — Apnoea from continuous ventilation in pigeons. (Lueiani and Bordoni.) A, Instan-
taneous transition from normal breathing to apnoea, as soon as ventilation commences at V.
B shows transition from normal respiration to apnoea, after ventilation had commenced at
point V.

(c) In fowls, apnoea is fairly dimcu-lt to obtain, no matter at
what pressure the pulmonary ventilation is effected. Generally
speaking, it is invariably incomplete, and respirations of an
extremely limited character can always be detected, showing
persistence of rhythmical activity in the centres (Fig. 222, A).

FIG. 2'21.— Gradual and delayed return of normal respiration after prolonged period of
apnoea in pigeons. (Lueiani and Bordoni.)

Here also the return to the normal is preceded by an increase
(Fig. 222, B).

(d) The apnoea of birds from continuous ventilation is, like that
of mammals (Berns), immediately interrupted by the insufflation
of a minute quantity of carbonic acid, as also by the momentary
closing of the ventral aperture, or of the inflating tube, or by
excitation of the vagi in the neck (Fig. 223).

(e) When pulmonary ventilation is effected with pure oxygen
instead of air, at a pressure of 1 mm. Hg, complete apnoea is never
produced in pigeons (Fig. 224, A) ; at a pressure of 2 mm. Hg

486

PHYSIOLOGY

CHAP.

apnoea is produced suddenly or with a short decrease ; but the
resumption of respiration is preceded almost invariably by general
movements of the animal, without the gentle and regular increase
that always succeeds the apnoea produced by air (Fig. 224, B).
Often the return occurs with periodic respiration, which soon dies
away, and is replaced by the ordinary rhythm (Fig. 224, C).

(/) After section of the vagi, complete and persistent apnoea
can no longer be obtained in birds, either by inflation with air, or

FIG. 222. — Effects of continuous pulmonary ventilation in fowls. (Luciani tincl Bordcni.) A,
Incomplete apnoea after ventilation commencing at V; B, gradual return to normal respira-
tion, after insufflation ceases, at <"•

with oxygen, no matter at what pressure the ventilation is
effected. Eespiration becomes weakened to a very marked extent
in pigeons, and to a less degree in turkeys and fowls (Fig. 225, A,
B, C). If the vagi are divided during apnoea, it will usually persist
for a certain time, owing perhaps to the effect of operative
traumatism. Sometimes, however, the respiratory movements are
reinstated immediately after section of one vagus (Fig. 226).

FIG. 223. — Effect of passing a small amount of CO* through the respiratory passages, during
apnoea from continuous ventilation, in turkeys. (Luciani and Bordoni.)

Most of the interpretations of respiratory rhythm suggested
from Kosenthal onwards (Pfliiger, Hering, Kosenbach, Burkart,
Marckwald/Gad, etc.) start with the fundamental concept that
not only nutrition, but also functional activity, is maintained
in the respiratory centres by the blood circulating in them,
which, when normally constituted, acts as an external stimulus,
i.e. it contains stimulating factors such as carbonic acid or the
other products of tissue consumption. This general theory is
always based on the apnoea which inevitably sets in when

xiii KESPIKATORY RHYTHM 487

these stimulating matters have to any considerable extent been

pa .2
35

So
i

'

f

p^a K

II

S5

removed from the blood, so that it no longer acts as an effective
stimulus.

488

PHYSIOLOGY

CHAP.

The analysis of the different cases of respiratory rhythm which
we have so far been examining rather lead us, on the other hand,
to the conclusion that no apnoea is exclusively determined by the
diminished venosity of the blood. Even the apnoea of birds
produced by continuous ventilation, which Miescher considered
the most typical case of true apnoea, is, according to our results,
a complex effect, essentially determined by a vagus reflex.
Indeed, when the pressure by which pulmonary ventilation is
effected is strong enough, it is instantaneously produced, without
any gradual diminution of the respiratory acts, i.e. before any
decarbonisation of blood can have taken place. Accordingly,
it must depend essentially on reflex excitation by the centripetal

Fio. 225. — Effect of continuous ventilation after section of vagi in birds. (Luciani and Bordoni.)
A, In pigeon ; B, in turkey ; C, in fowl. In all three tracings the insufflation of air commences
at V.

paths from the lungs and air-sacs, in which the air is normally
but little regenerated, and which, accordingly, are highly sensitive
to the passage of air, even at low pressures.

In fowls apnoea is hard to obtain, perhaps because their air-
sacs are less sensitive to the mechanical action of air. Striking
evidence of this theory is afforded by the fact that after section of
the vagi it was no longer possible to obtain complete apnoea in any
of the birds experimented on. The decarbonisation of the blood
reduces the respiratory processes considerably, but it does not
suppress them, which upsets the usually accepted theory that
respiratory rhythm is maintained by the external stimuli of the
blood or interstitial lymph, circulating in the centres.

No less interesting (although of doubtful significance) is the

-r. o

xin KESPIEATOEY EHYTHM 489

fact that with intact vagi it is not possible to obtain complete

apnoea, when continuous ventilation is made

with pure oxygen instead of air. Is it possible

that oxygen lowers the tone or paralyses the

afferent fibres of the vagi, so that the respiratory

centres resume partial or total independence of

their rhythmical and alternate messages ? Or

does oxygen perhaps excite the peripheral

extremities of these nerves to such an extent

as to throw into reflex activity other centres,

which in functioning counteract the inhibitory

messages to the centres of respiration ? The

general movements and restlessness of the

animal on ventilation with oxygen, rather tends

to support this second hypothesis. At all

events this curious phenomenon is a fresh

argument towards showing that the decarbon-

isation of blood and its marked arterialisation

is not enough to check the rhythmical and
alternate activity of the respiratory centres.

Ehythmical and alternate activity! That
is to say, rhythmical activity of the inspira-
tory centres, alternating with rhythmical
activity of the expiratory centres, even in
apnoea, even during the quiet expiration of
sleep ! This fact — which, as we have seen, was ^^^^^

clearly demonstrated by Aducco — excludes the ^^|^^H 1 1
assumption that the mechanical activity of
respiration depends upon any kind of external
stimulus. So that it does not appear to us
possible, in explaining the alternate activity of
two centres that are antagonistic in action, to
invoke as a causal factor an external stimulus
of any kind whatsoever, acting continuously
upon these centres.

We can only conclude that the activity of ^^^^^^^
the said respiratory centres depends essentially IBH
upon the special intrinsic organisation of the
elements of which they are composed. ^^^^^^^

These elements are not merely endowed
with reflex excitability, i.e. are thrown into
excitation by simple external stimuli, coming
to them in the form of nervous vibrations
from the periphery of the centripetal nerves,
or as the chemical products of tissue con-
sumption acting directly upon those tissues ; but they also possess
automatic excitability properly so-called, i.e. they are capable of

03 r-

490 PHYSIOLOGY CHAP.

reacting to internal stimuli, by intrinsic variations in their
metabolism.

This logical deduction from a long series of premisses appears
at first sight to be contradicted by some of Fredericq's latest
experiments (1901). He claims to have obtained true apnoea upon
dogs, by eliminating (with the simple reduction of the carbonic
acid of the blood circulating in the centres) certain mechanical
causes that act through the afferent paths of the pulmonary vagi.

The experimental method which he employed for this purpose
is extremely ingenious, although not easy to carry out. It consists
in establishing between two dogs the so-called crossed cephalic
circulation. It is necessary to connect the carotids of the animals
by glass cannulae and rubber tubes (after ligaturing the vertebral
arteries, and rendering the blood incoagulable by injections of
pro-peptone) so that the central end of the carotid in one and the
peripheral end of the carotid in the other are brought together,
•and vice versa. The blood being circulated in this new system, it
follows that the brain -of the first animal is irrigated by the
greater part of the blood derived from the heart Of the other
animal, and vice versa.

Under these conditions, Fredericq observed that the artificial
increase and reduction of venosity in the blood of one of the dogs
affected the respiratory centres of the other, which exhibited
dyspnoea or apnoea respectively. If, e.g., the trachea was compressed
in dog A so as to produce asphyxia in that animal, the blood
surcharged with waste products, on reaching the brain of dog B,
determined a violent dyspnoea, while dog A continued to breathe
quietly, or showed a slight inclination to apnoea, its centre being
irrigated with blood from B which was highly arterial, in conse-
quence of the dyspnoeic respiration of the latter.

If, on the contrary, profound artificial respiration with the
bellows is performed on dog B, perfect apnoea is seen on dog A,
which, according to Fredericq, can only depend upon the reduced
venosity of the blood circulating in its respiratory centres from
the^heart of B, all abnormal mechanical action of the lungs being
thus eliminated in A (Fig. 227).

On determining with the aerotonometer the state of the gases
in the blood of dog A during artificial respiration, Fredericq found
a slight rise in the percentage content of oxygen, and conversely
a marked reduction (by more than half) in the percentage of
carbonic dioxide. From this he concluded that the apnoea that
obtains during crossed cephalic circulation is exclusively deter-
mined by diminished tension in the carbonic acid of the blood.
Have we here, for the first time, evidence of a true apnoea, in
Miescher's sense, determined by the state which Mosso calls acapnia?

On carefully considering the experimental conditions of
Fredericq's method it becomes apparent that he is far from

xin RESPIRATORY RHYTHM 491

having demonstrated that the respiratory acts are normally deter-
mined by the carbonic acid circulating in the centres. Baglioni
and Winterstein aptly pointed out that in Fredericq's experiment
the vagi were left intact. Now, when the excitability of the
respiratory centres is altered, it is quite conceivable that the
excitations of the pulmonary terminations of the vagi, which
normally exert a reflex control over the acts of respiration, may
determine an inhibition of the centres, and thus produce spurious
apnoea. That in Fredericq's cases the excitability of the centres
was enormously depressed may be inferrecNhrom the narcosis (due
to the morphin or chloroform administered), the operations
necessary to produce the crossed circulation in the brain, the
diminished blood-supply to the brain (ligature of vertebral

FIG. 227. — Pneumograms obtained from two Knoll's pnetimographs in two dogs (A and B) during
experimental crossed circulation. (Fredericq.) The blood from trunk of B circulates in head of
A; that from trunk A in head B. Each application of artificial respiration in B produces a
short period of apnoea in A.

arteries), and lastly, the general intoxication of the centres due
to the injection of pro-peptone, which induces a quasi-comatose
state. It is also conceivable that under such conditions the sum
of the excitations which reach the bulbar centres continuously
by the afferent paths of the pulmonary vagi, the muscles, fascia,
tendons, determine a brief inhibition of the respiratory movements.
We say brief, because Fredericq has not demonstrated that pro-
longed artificial respiration in dog B determines any apnoeic state
of corresponding duration in dog A.

The tracings of Fig. 22*7, on the other hand, demonstrate that
in two repeated experiments five strong pulmonary insufflations
on dog B determine a suspension of respiration in dog A lasting
8-10 seconds, after which natural respiration re-commences very
feebly, in accordance with the depressed excitability of the centres.

492

PHYSIOLOGY

CHAP.

XV. Just as the phenomenon of periodic cardiac rhythm
supplied the most direct argument in favour of the theory of the
automatic functions of the heart, so that of
periodic respiration, or, at least, of certain
forms which it may assume, gives us direct
evidence of the automaticity of the respir-
atory centres.

Periodic respiration, in its most classic
form, as first described by the English
physicians Cheyne and Stokes (1816-1854),
consists in an alternation of apnoea and
dyspnoea, of pauses and groups. Each group
A of respirations shows a rise and successive
| fall of intensity as well as frequency. The
| first and last respirations are minimal or at
5 any rate quite shallow, while the central
§ respirations are deep or highly dyspnoeic.
Each group may reach a maximum of 20-30
respirations. The duration of 'the pauses
§ may be equal to, less than, or greater than
B that of the groups; but it is always above
| 40-50."

\ These classical cases of periodic group-

-. ing of the respiratory acts are rare, and are
| usually met with in serious disease of the
| brain and heart, in the comatose period of
I* certain acute infections, and in the later
£ pre-agonic stage of various diseases. A
2 typical case of Cheyne-Stokes breathing is
g that observed by Gibson (Fig. 228) in a man

1 suffering from chronic renal disease of the
f' kidneys. Less intense forms, on the con-
8 trary, in which the groups are represented

2 by a few respirations and the pauses give
intermittency for a few seconds (Fig. 229 A)
are tolerably frequent. The pauses may even
be absent, when the periodicity of breathing
is reduced to the rise and fall in intensity
of the respiratory acts, which succeed with
a certain rhythm, with no positive distinc-
tion of groups and pauses (Fig. 229, B).

The most important thing to note in all
these forms of periodic respiration is that
the duration of the pauses is not in any
relation with the duration or number of the
respirations in the groups. Of great significance, again, is the fact
that the form of the groups may vary considerably ; sometimes

XIII

KESPIKATOKY EHYTHM

493

they exhibit an increment and decrement (Fig. 230) ; at other
times an increment alone (Fig. 230) ; at others a decrement alone
(Fig. 231) ; at others again the respirations of the group all exhibit
much the same intensity.

FIG. 229. — Periodic respiration observed in man at high altitudes. (Mosso.) A, Tracing obtained
with Marey's pneumograph on Mosso himself when awake, at 3620 metres. B, Tracing taken
during light sleep from watchman at the Regina Margherita hut, 4500 m.

Periodic respiration is not essentially a morbid phenomenon.
It invariably accompanies the lethargy of hibernating animals
(Mosso, Fano, Langendorff, Patrizi) ; is sometimes seen in the sleep

FIG. 230. — Periodic respiration in man. (A. D. Waller.) The rotating cylinder moves slowly.
The signal marks minutes on abscissa.

of healthy individuals, particularly in old people and children
(Mosso) ; often at high altitudes (2500-4500 m. above sea-level) ;
it is observed conspicuously in sleep (Fig. 231), and in a less degree
in waking (Egli-Sinclair, Mosso).

A number of attempts have been made to evoke experimental

494

PHYSIOLOGY

CHAP

periodic respiration in man or other animals. Flourens (1842)
accidentally observed periodic respiration in an animal on which,
after extirpating the brain, the two vagi had been divided. M.
Schiff (1859) described the same phenomenon in mammals after
copious haemorrhage and pressure exerted upon the medulla
oblongata.

Traube (1871) induced periodic respiration in cases of heart

Fia. 231.— Periodic respiration observed on U. Mosso during sleep, 4o60 metres.

disease by hypodermic injection of morphia, and increased it by
the same means in patients who already exhibited the phenomenon.

In 1874 we obtained the same effect in dogs, by giving them
intravenous injections of laudanum and subsequent artificial
respiration sufficient to produce apnoea (Fig. 232).

Filehne and Heidenhain (1874) simultaneously obtained it in
dogs and rabbits with intravenous injections of chloral hydrate.

Fio. 232.— Periodic respiration in dog anaesthetised by intravenous injection of u c.c. laudanum.
Tracheotomy was performed after previous production of apnoea by artificial respiration with
the bellows. (Luciani.) The tracing was obtained by connecting the tracheal tube with a
receiver containing 30 litres of air, joined to a writing tambour.

Cuffer (1878), who had noticed the frequent coincidence of the
respiratory phenomenon with interstitial nephritis, succeeded in
provoking it in dogs by intravenous injections of creatine and
ammonium carbonate. Smirow (1884) obtained it in dogs with
inhalations of sulphuretted hydrogen ; Langendorff (1881) with
injections of muscarine and digitaline; Bordoni (1886) with
injections of scillaine and gelsemine, on frogs and toads.

After discovering the cardiac phenomenon in the frog (1872-
1873, in Lud wig's laboratory) we attacked the experimental study

xin RESPIRATORY EHYTHM 495

of the respiratory phenomenon, with the object of verifying whether
the two effects (which present such a marked analogy) had a
common origin. Since the cardiac effect is instantly and con-
spicuously obtained upon the isolated heart perfused with serum,
when the most automatic part of the frog's heart is cut off by a
ligature, we inquired whether the respiratory effect would be
produced, on transversely dividing the spinal bulb in the rabbit,
above the origin of the vagus nerves, so as to separate its highest
segment from the respiratory centres. These investigations
(c'arried out like the former in Ludwig's laboratory) were long
and laborious, because not always successful. Sometimes we
obtained respiratory standstill, immediately or soon after the
section. At other times there was no radical modification of
respiratory rhythm, which (although it became irregular and pro-
gressively slow and shallow till death occurred) never presented
the peculiar grouping characteristic of Cheyne-Stokes breathing.

FIG. 233. — Periodic respiration in rabbit, after transverse section of bulb at level of visible apex
of alae cinereae. (M. Marckwald.) Tracing taken with phrenograph. The ascending curves
correspond with the contractions of the diaphragm.

But in other more fortunate cases it did appear in the form
of groups, which exhibited no increment but merely a rapid
decrement followed by the pause. The- number of respirations
in the successive groups increased or diminished somewhat
irregularly ; at the same time the pauses became now longer, now
shorter than the groups. In the most successful experiment,
however, we were able to watch the tendency of the groups to
become gradually smaller, and of the pauses to shorten, till the
crisis of the phenomenon set in, when the groups resolved them-
selves into a series of staccato respirations separated by long
pauses, and progressively decreasing till death ensues. The vary-
ing position of the section on the bulb, and the different degrees
of the consequent haemorrhage, appear to us sufficient to account
for the difference in results.

Marckwald (1888) obtained precisely similar results in
Kronecker's laboratory on separating the medulla oblongata from
the rest of the brain at a level above the respiratory centres of

496 PHYSIOLOGY CHAP.

the rabbit. When the section falls at the level of the apex of the
alae cinereae, respiration immediately becomes periodical. After
long pauses groups of three, four, or five respirations occur, which
decrease in depth (Fig. 233). On dividing the medulla at a
higher point, periodic respiration may sometimes be observed when
pressure is exerted on the respiratory centres by the extravasation
of blood in the neighbourhood of the alae cinereae. On removing
the clot ordinary respiration is reinstated. Sometimes, after section
of the bulb, respiration will at first be normal and subsequently
become periodic, perhaps owing to the exposure of the bulb to air.
In conclusion — no essential difference from the results we pub-
lished eight years previously.

In 1874, on studying the course of asphyxia in narcotised and
tracheotomised dogs, with intact or divided vagi, making them
breathe into a large closed receiver, which transmitted the respiratory
movements to a writing tambour, we not infrequently observed, in
the final moments before the death of the animal, the formation
of a series of small groups consisting of two respirations, the first
being somewhat deeper than the second, separated by pauses
occupying a period about three times as great as that of the
groups (tracings similar to that of Fig. 231). So that the mode
in which the vitality of the respiratory centres dies out in
asphyxia recalls the modus moriendi of the frog's heart, when
excised and filled with serum that is never regenerated (see
Chap. IX. 3).

In 1880 Sokolow and Luchsinger published their ingenious
researches on the respiratory phenomenon observed in the frog,
during asphyxia of the centres from ligature of the aorta, and
during the resumption of activity when the ligature has been
removed. They noticed that in the first case the number of
respirations in the successive groups diminishes, while the subse-
quent pauses are prolonged ; in the second case the opposite occurs,
i.e. the groups become progressively larger and the pauses shorter
until normal rhythmical respiration is resumed. We have no
information as to the form of the groups, the authors not having
employed the graphic method.

The important researches of Fano, carried out in our laboratory
at Florence in 1883, on the periodic respiration of tortoises,
agree perfectly with those of Sokolow and Luchsinger, although
they grew out of a side issue. After excising the heart of a big
land tortoise he saw that the animal continued to breathe, no
longer rhythmically, but in groups separated by long pauses.
Periodic respiration (though of a highly irregular character in
regard to number of respirations and duration of groups and
pauses) is very frequently observed, both in land and water
tortoises, during the winter lethargy. In the majority of groups
the respirations present much the same amplitude, and none of

xin EESPIKATOBY KHYTHM 497

them exhibit the characteristic rise and fall of the classical Cheyne-
Stokes phenomenon (Fig. 234).

On trephining the carapace of such an animal, opening the
pericardium and ligaturing the pulmonary artery and the two
aortae with a single thread, so as to arrest the circulation, the
respiratory phenomenon continues ; the pauses lengthen, the
groups shorten, so that the periodicity of the rhythm becomes
more marked.

When these hibernating tortoises are made to breathe in-
different gases such as nitrogen and hydrogen, instead of air or
pure oxygen, the periodic respiration continues to be of the same
character ; dyspnoea is entirely absent, while the number of
respirations in the time unit becomes much less. Respiration
with indifferent gases may be kept up for a long time, without
cessation of life in the animal. Thus, e.g., a tortoise continued to
breathe for two days in an atmosphere of pure nitrogen.

None the less, protracted respiration of asphyxial or toxic
gases, such as carbonic acid and carbon monoxide, does suppress

Fio. -234.— Periodic respiration in hibernating tortoise. (Fano.) Pneuniograms obtained by
letting animal breathe from small receiver, connected with a writing tambour.

periodic respiration in the hibernating tortoise. «vln certain cases
carbonic acid produces an inclination to dyspnoea, but only of
brief duration. In all cases, whether suddenly or after a short
time, the pauses become longer, the groups of respirations less
frequent and smaller, until they die out. A water tortoise
breathed 18 litres of carbon monoxide for :36 hours. It was
removed from the apparatus after its breathing had ceased for
about an hour ; yet it was still alive, and after a little time began
to breathe again and to move spontaneously. When killed and
dissected it showed the most unmistakable signs of carbon
monoxide poisoning.

When a hibernating tortoise is chloroformed, there is a rapid
and progressive diminution in the groups of respirations till
absolute standstill of the respiratory centres is obtained. Chloro-
form, the "reagent for vital excitability," as it was termed by Cl.
Bernard, attacks the innermost conditions of the activity of the
nerve-centres, removing from the respiratory centres in a short
time their capacity to liberate the energy which they accumulate
by the accustomed paths.

VOL. I 2K

498 PHYSIOLOGY CHAP.

XVI. Periodic respiration is a physio-pathological phenomenon
intimately connected with the difficult problem of the nature of
the normal rhythmical functions of the respiratory centres. Th/$,
first to perceive the importance of this point was Traube, to whose
initiative is due the harvest of literature on this interesting
subject, which we have briefly summarised.

In 1879 we drew up an exhaustive refutation of Traube's
doctrine, and of the more complicated theory opposed to it by Filehne
in 1874, showing the absolute inadequacy of these hypotheses to
account for the whole of the experimental data, and the great
variety of clinical forms, which the respiratory phenomenon may
assume. We showed that it was impossible, in face of the proved
facts, to solve the problem by the postulate usually admitted and
defended, to the effect that the capacity and functional activity of
the central mechanisms of respiratory rhythm are always in
direct and immediate dependence upon extrinsic conditions of
stimulation and nutrition ; i.e. in other words, that the said
centres merely transform what at any given moment they receive,
in the same degree and with the same rhythm at which they
receive it. The experimental evidence shows that there is,
between the external action and the reaction, a whole, complex,
chemico- molecular, internal process, of which we are aware in
virtue of its results, but as to the laws of which we are entirely
ignorant.

The obvious facts on which we have insisted amply suffice to
prove that there is no ratio between the duration and the degree
of pulmonary ventilation represented by the groups and the
duration of the pauses ; that the form of the groups may vary
greatly and in opposite ways that are not comparable inter se ;
that periodic respiration may be observed even where no gas
exchanges between the atmosphere and the blood are possible
— all these clearly demonstrate the fundamentally automatic
character of the function of the bulbar respiratory centres. " The
different forms that may be assumed by the respiratory rhythm,
including those of periodic grouping, are merely the external
expression of corresponding modes of oscillation in the nutritional
processes, which are carried on within the depths of the respiratory
centres " (Luciani, 1879).

Normally, however, these centres, in addition to an automatic
excitability, are provided with a most delicate reflex excitability,
which enables them immediately to react even to the slightest
external stimulus, thus giving rise to profound modifications in
the form and rhythm of the automatic excitability as dependent
upon the internal impulses. Our task is now to determine (as
precisely as possible) what are the relations of co-existence
of these two forms of excitability, both in normal conditions, and
under exceptional or abnormal conditions, of the respiratory centres.

xin RESPIRATORY RHYTHM 499

The normal respiratory rhythm of man and other homothermic
animals in general is essentially conditioned by the reflex activity
of the centres. In eupnoea it is the established auto-regulation of
the vagi that predominates, i.e. the mode in which the air that
passes rhythmically through the lungs in a certain time is
distributed, depends on the rhythmical and alternate impulses
that reach the centres from the peripheral extremities of the
pulmonary vagi. The proof of this lies in the fact that normally
the nervous and muscular mechanisms of the thoracic movements
are always active ; inspirations alternate with expirations without
pause or intermediate rest (cf. tracings of Figs. 184, 185, 186, on
pp. 418, 420, 421), as if the excitation passed from the inspiratory
to the expiratory centres, and vice versa, by an uninterrupted
reciprocal, intercentral transmission, and with a delay that just

FJ«. -23.J.— Thoracic respiration of a soldier, recorded with Marey's'pneuniograph

at 4560 metres. (A. 3Iosso.)

suilices for the two antagonistic movements to succeed without
coincidence.

Under certain special conditions, however, tins perfect eupnoea
fails, probably in consequence of a diminished sensibility of the
afferent fibres of the vagi, which renders the impulse transmitted
to the inspiratory centres from the expiratory position of the
lungs nil or inadequate. In this case there is between the end of
expiration and the commencement of inspiration a more or less
prolonged pause. This phenomenon, which we believe to be not
uncommon in clinical cases, was recorded graphically by Mosso in
two robust soldiers during rest upon the High Alps (4560 m. above
sea-level), as shown in the tracing of Fig. 235. We do not
interpret this as meaning that at high altitudes one breathes less,
since it is shown elsewhere that " at high altitudes no important
modifications in the output of carbonic acid and the .intake of
inspired air occurs." Until the contrary is proved, we hold it
logical to assume that the phenomenon described depends upon a

VOL. i 2 K a

500 PHYSIOLOGY CHAP.

paretic state of the vagus, determined by the altitude. In this
case the eupnoea is no longer perfect, and the iuspiratory acts are no
longer determined by the nervous vibrations that ascend by the
afferent paths of the vagus to the centres, but by a certain degree
of venosity acquired by the blood circulating in them during the
expiratory pause.

While the intermittent excitations via the centripetal nerve-
paths determine particularly the frequency of rhythm, i.e. the distri-
bution of the total air that passes through the lungs in the time
unit, the chemical excitation produced by the venosity of the blood
especially determines the intensity of the rhythm, i.e. the total
quantity of air breathed in the time unit. The theory of dyspnoea
agrees perfectly with this conclusion. In dyspnoea, in general, and
particularly in that determined by the increased production of
carbonic acid, the reflex excitability of the centres comes into
play, and causes automatic excitability to become latent by
adapting the respiratory rhythm to the chemical needs of the
organism.

As in apnoea and dyspnoea the factor of the central- excitations
determined by the amount of the external stimuli predominates,
so in tachypnoea and apnoea the factor of increased, or diminished,
excitability predominates, owing to which the centres become more
sensitive, or refractory, to the action of the said stimuli.

But the excitability of the centres (whether automatic or
reflex) is an oscillating quantity, which follows closely, and is, so
to speak, modelled on all the vicissitudes of the intimate metabolic
processes. Each explosion of energy that accompanies a katabolic
disruption determines a relative degree of resistance in the
centres to external and internal stimuli ; each accumulation of
energy, determined by an anabolic construction, increases their
susceptibility to the same. Further, these respiratory tracings
show not merely the rhythmic and alternate activity of the
antagonistic respiratory muscles, but they sometimes, particularly
after the action of certain poisons, exhibit slow positive and
negative oscillations in the tone of the said muscles, which recall
the oscillations of tone in the auricles, as described by Fano, and
in the vessels, as described by Schiff and by Traube and Hering.
This is well illustrated in the tracing of Fig. 236, registered
by Mosso from a rabbit intoxicated with piridine. Under normal
conditions these oscillations in the tone of the respiratory muscles
are absent, but occasionally they become visible in sleep as in
Fig. 237- These slow oscillations in the tone of the muscles
are the external expression of the corresponding oscillations of
excitability (automatic and reflex) in the respiratory centres.

As soon as these oscillations of excitability of the centres are
exaggerated, the phenomenon of Cheyne-Stokes breathing sets in.
The pauses depend essentially upon the depression of excitability

XIII

EESPIEATOEY EHYTHM

501

below the threshold, at which the external and internal stimuli
are inadequate to throw the central organs into excitation ; the
groups appear when, owing to rise of excitability, the external and
internal stimuli again become effective (Luciani, 1879). The
same theory of periodic respiration was formulated almost
simultaneously by Eosenbach (1880) ; by Sokolow and Luchsinger

FIG. 236. — Oscillations of tone in respiratory muscles in rabbit poisoned with piridine. (Mosso.)
R, respirations recorded with a Marey's tambour applied to xiphoid process. F, tracing of
blood pressure in carotid, recorded simultaneously with a mercury manometer. The pro-
nounced oscillations of respiration are seen not to be associated with perceptible altera-
tions of blood pressure.

(1880), who endeavoured to reinforce it by ingenious marshalling
of the facts; by Langendorff and Siebert (1881), who confirmed
and developed the work of their predecessors ; lastly, by A. Mosso
(1885), who resumed and consolidated it by new observations.

Fio. 237.— Thoracic respiration in sleep of robust subject, recorded with Marey's pneumograph ;
shows periodic oscillations of both inspiratory and expiratory excursions. (A. Mosso.)

Zuntz (1882) correctly pointed out the great analogy between
the classical phenomenon of Cheyne-Stokes respiration and the
alternation of sleep and waking. Sleep corresponds with the
pause, the waking state with the group. Just as complete
awakening is preceded by an ascending phase of waking up,
and sleep is preceded by a descending phase of drowsiness, so
the Cheyne-Stokes phenomenon shows increase and decrease.

VOL. i 2 K I

502 PHYSIOLOGY CHAP.

Mosso has pointed out other yet more convincing analogies from
clinical observation. In sleep the pupils contract, the eyes rotate
inward and upward; in the waking state the pupils dilate, the
eyes rotate outward (Fontana). Just so in periodic respiration,'
when the pause commences, the pupils retract, the eyes converge
inwards and upwards; when the group commences, the pupil
dilates, the eyes look forward (Leube). At the beginning of the
pause some patients are drowsy and become insensible ; ab the
beginning of the group they are restless, and again suffer pain
(Leube, Merkel). Certain subjects close their eyes at the termina-
tion of the group, at the commencement of the pause, and in the
midst of it, and open them again at the commencement of the
group or soon after (Frantzel, Hein, Kaufmann). In more serious
cases the stupor and unconsciousness are continuous throughout
the Cheyne- Stokes breathing ; in other cases consciousness
returns, partly at any rate during the groups ; in others, lastly, the
respiratory phenomenon takes place in the awakening state.
These are differences of intensity, shades and gradations of one
fundamentally identical process, which explains why t.he patient
now reacts and now fails to respond to external stimuli during the
periodic pause. " The pause," writes Mosso, " always implies a
more or less serious drowsiness of the nerve centres," which is as
much to say, in more exact and strictly physiological language,
that during the pauses the respiratory centres suffer a negative
variation in their excitability. Reflex excitability, automatic
excitability, or reflex and automatic excitability together? The
answer to this important question necessitates some consideration.
Let us consider the extremes. In many cases, whether clinical
or experimental, of periodic respiration, the reflex excitability of
the centres is maintained. Sometimes it is sufficient to invite the
patient to breathe, or to excite him with acoustic, luminous, thermal
or painful stimuli, during the pause, in order immediately to cut it
short, and obtain respiratory movements (Biot, Saloz, Murri,
Bordone). In rabbits with divided bulb which breathe periodically,
faradisation of the centres, with strong and infrequent break
shocks, will produce respiratory movements, either during the
groups or during the pauses (Kronecker and Marckwald). These
facts do not, as some maintain, contradict the theory that periodic
respiration depends essentially upon periodic oscillations in the
excitability of the centres, because the substitution of artificial for
natural stimuli probably involves disturbance of the whole of the
intimate and delicate metabolic process on which the periodic
grouping of the central impulses that determine Cheyne-Stokes
respiration depends ; -but it has certainly been demonstrated that
the reflex excitability of the centres, though reduced, is not
suspended, during the pauses in these cases. Accordingly, it must
be assumed that the periodic quantitative variation in the external

xiii KESPIKATOKY EHYTHM 503

stimuli acting on the centres, can and must co-operate with the
functional intermittence characteristic of these centres, owing to
the alternations of groups and pauses.

The other extreme cases of periodic respiration are the
experiments of Sokolow and Luchsinger, and of Langendorff and
Siebert on the frog, and more particularly those so admirably
carried out by Fano on the tortoise. In these cases the reflex
excitability of the centres (particularly the capacity of reacting to
the stimulus of the blood) is not merely lessened, but is entirely
suspended. Here, then, periodic respiration is a more simple
phenomenon : when reflex excitability is suspended, the automatic
excitability of the centres dominates the stage completely, and the
grouping of the respirations is the external expression or record of
the special mode in which the energy accumulated within them —
in consequence of the slow processes of metabolism — is liberated
and developed, until it is finally exhausted. The importance of
the facts adduced by Fano consists not in any refutation of
the theory formulated by us in 1879, which is left untouched
because it deals with an essentially distinct order of phenomena ;
but in its demonstration that the two forms of excitability with
which the elements of the respiratory centres are endowed do not
suffer from the vicissitudes of metabolism in the same degree,
since in poikilo thermic animals, under certain special conditions,
reflex activity may be entirely suspended, or profoundly depressed,
while automatic excitability persists and is manifested by char-
acteristic upward and downward fluctuations.

This lengthy chapter has been exclusively devoted to the
nervous factors of the respiratory mechanism. But a further
series of important facts shows that the chemical respiratory
activity of the tissues is also dominated by the nervous system,
which may excite or moderate it, and even cause the value of the
respiratory quotient, i.e. the ratio between the oxygen absorbed
and the carbonic acid given off, to oscillate.

We shall consider this interesting subject, which exceeds the
limits of the physiology of the respiratory apparatus, in due time,
along with the metabolism, or material exchanges, of the body as a
whole.

BIBLIOGRAPHY

The following monographs and memoirs are most frequently quoted from the
copious literature of this subject : —

FLOURENS. Recherches experimentales sur les proprietes et les fonctions du

system e nerveux. Paris, 1842.
BROWN-SEQUARD. Journal de physiologie, i., 1858.
M. SCHIFF. Lehrbuch der Physiol., 1858-59. Gesam. Beitrage zur Physiol., i.

Lausanne, 1894.
ROSENTHAL. Die Atembewegungen und ihre Beziehungen rzum Nervus vagus.

Berlin, 1892. Hermann's Handbuch d. Physiol., iv. Leipzig, 1882.
HERING and BREUER. Sitzungsber. d. Wiener Akademie, Ivii., ii., 1868.

504 PHYSIOLOGY CHAP, xm

PFLUGER. Archiv f. d. ges. Physiol., i., 1868.

TRAUBE. Gesammelte Beitrage, ii. Berlin, 1871.

EWALD. Archiv f. d. ges. Physiol., vii., 1873.

GIERKE. Archiv f. d. ges. Physiol., vii., 1873.

LUCIANI. Lo Sperimentale. Firenze, 1879.

SOKOLOW and LUCHSINGER. Pfliiger's Arch., xxiii., 1880.

LANGENDORFF and SIEBERT. Du Bois-Reymond's Arch. f. Physiol., 1881.

GAD. Du Bois-Reymond's Arch. f. Pysiol., 1880-81-85-86.

FANO. Lo Sperimentale. Firenze, 1883-84-86.

MIESCHER. Du Bois Reymond's Arch. f. Physiol., 1885.

Mosso. R. Accademia dei Lincei. Roma, 1885. Fisiologia dell' uomo sulle Alpi.
Milano, 1898.

ZUNTZ and GEPPERT. Pfliiger's Arch., xxxviii., 1886.

MARCKWALD. Zeitschrift fiir Biologic, 1887. (Contains summary of publications
to that date.)

BORDONI. Lo Sperimentale. Firenze, 1888.

STEFANI and SIGHICELLI. Lo Sperimentale. Firenze, 1888.

ADUCCO. Annali di freniatria e scienze affini. Torino, 1889.

GAD and MARINESCO. Du Bois-Reymond's Arch., 1893.

GIBSON, G. A. Cheyne-Stokes Respiration, 1882.

LEWANDOWSKY. Du Bois-Reymond's Arch., 1896.

FREDERICQ. Arch. d. Biol., 1900-1.

NEANDER. Skandin. Arch. f. Physiol., ii., 1902.

BAGLIONI. Centralbl. f. Physiol., 1903. Zur Analyse der Reflexfunktion, Wies-
baden, 1907.

BORUTTAU. Ergebnisse der Physiol., i. and iii,, 2, 1902, 1904.

N. ZUNTZ, A. LOEWY, F. MULLER, W. CASPARI. Hohenklima und Berg-
wanderungen, 1906. Bong & Co.

Recent English Literature :—

W. J. GIES and S. J. MELTZER. Studies on the Influence of Artificial Respiration

upon Strychnine Spasms and Respiratory Movements. Amer. Journ. of

Physiol., 1903, ix. 1-25.
W. E. DIXON and T. G. BRODIE. Contributions to the Physiology of the Lungs.

Part I. The Bronchial Muscles, their Iimervation and the Action of Drugs

upon them. Journ. of Physiol., 1903, xxix. 97-173.
I. H. HYDE. Localisation of the Respiratory Centre in the Skate. Amer.

Journ. of Physiol., 1904, x. 236-258.
J. S. HALDANE and J. G. PRIESTLEY. The Regulation of the Lung Ventilation.

Journ. of Physiol., 1905, xxxii. 225-266.
I. H. HYDE. A Reflex Respiratory Centre. Amer. Journ. of Physiol., 1906,

xvi. 368-377.
G. N. STEWART and F. H. PIKE. Resuscitation of the Respiratory and other

Bulbar Nervous Mechanism with Special Reference to the Question of their

Automaticity. Amer. Journ. of Physiol., 1907, xix. 328-359.
G. N. STEWART and F. H. PIKE. Further Observations on the Resuscitation of

the Respiratory Nervous Mechanism. Amer. Journ. of Physiol., 1907-8,

xx. 61-73.
G. N. STEWART. Some Observations on the Behaviour of the Automatic

Respiratory and Cardiac Mechanisms, etc. Amer. Journ. of Physiol., 1907-8,

xx. 407-438.
C. G. DOUGLAS and J. S. HALDANE. The Causes of Periodic or Cheyne-Stokes

Breathing. Journ. of Physiol. , 1909, xxxviii. 401-419.]
C. G. DOUGLAS and J. S. HALDANE. The Regulation of Normal Breathing.

Journ. of Physiol., 1909, 420-440.

CHAPTER XIV

THE LYMPH, AND INTERCHANGES BETWEEN THE BLOOD AND
THE TISSUES

P* CONTENTS. — 1. Structure of lymphatic vascular system, lymph spaces,
sinuses and cavities. 2. Origin ; physical, morphological and chemical char-
acteristics ; qualitative and quantitative variations of lymph. 3. Lymphatic
circulation, and the various mechanical factors by which it is determined.

4. Formation of lymph from the blood capillaries, and the so-called lymphagogues.

5. Secretory theory of Heidenhain, and transudation theory of Colmheim.

6. Formation and modification of lymph by the tissues. 7. Lymphoid tissue,
follicles and lymphatic glands. 8. Bone marrow. 9. The thymus. 10. The
spleen. Bibliography.

No less important than the gas exchanges between the blood
and the tissues, to the life of the cells of which the latter consist,
is the exchange of solid matters in which the blood yields to the
tissues the substances necessary to their nutrition and restoration
(histogenic substances), and the tissues yield to the blood the
products of their elaboration, transformation, or consumption
(histolytic substances, anabolic and katabolic.)

The nutritive, like the respiratory, exchanges are almost
invariably accomplished by means of the lymph, which is the true
internal medium in which the elements of the tissues live.
Hence the study of the nutritive exchanges includes the study of
the lymph ; of the functions of the lacunar and vascular system
which contain it ; of the functions of the tissues and organs which
more particularly contribute to its formation and modifications ;
of the mechanical factors that are constantly setting it in motion
and renewing it, driving it out into the blood torrent. All these
will be discussed in the present chapter.

I. The Lymphatic System, discovered by Aselli, Pecquet,
Kudbeck, Bartholin, in the first half of the seventeenth century
(see Chap. VI. 6), is one of the most extended and most important
in the body. It embraces, not only the vessels, follicles, and
lymphatic glands, but also the whole of the connective tissues,
and the system of lacunae or interstitial spaces which exist in
every part of the body, particularly where there are more or less
loosely constituted connective tissues. Even the large serous

505

506

PHYSIOLOGY

CHAP.

cavities, such as the peritoneum, the pleura, the pericardium, the
meninges, and, generally speaking, the whole of the serous sheaths
that invest the organs, form part of the lymphatic system in the
widest sense of the word.

As regards the morphological questions, many of them very
complicated and much disputed, that arise over this system, we
must refer to treatises on anatomy and histology. Here we can
only summarise the general notions that are most intimately
connected with physiological problems.

From the structural point of view, we may distinguish in
the lymphatic system : the lymph vessels properly so-called, the
lymphatic capillaries, the parenchymatous lymph spaces, the large
lymphatic or serous cavities.

(a) The lymphatic vessels constitute a rich system of canals

FIG. 238. — Supra valvular swelling of. lymphatic in cat's mesentery, treated with silver nitrate.
(Ranvier.) The smooth muscular fibres which surround the vessel interlace in various
directions at the seat of the swelling.

which are very similar in the structure of their walls to the veins,
and like them are richly provided with valves, which open centri-
petally and close in a centrifugal direction. These are specially
abundant in the small lymphatic vessels, e.g. in those of the
mesentery. Above each valve the vessel is somewhat dilated, so
that when there are many valves the vessel assumes a moniliform
or beaded appearance. The muscle cells in the tunica media of
the vessel walls are for the most part arranged in a circular
direction ; but at the supra valvular points of dilation they run in
various directions, so as to form a network (Fig. 238). Like the
blood-vessels, the lymphatics lie in a bed of connective tissue, and
gradually unite into vessels which become increasingly larger, until
they finally converge (in man and in the higher vertebrates) into
two principal channels: the thoracic duct, which opens by an
orifice provided with valves into the left subclavian vein ; and the
right lymphatic trunk, which opens into the right subclavian vein.
The lymphatics from the right side of the head and neck, right arm

xiv THE LYMPH 507

and lung, right side of thorax, and heart, and part of the upper
surface of the liver, unite in the right lymphatic trunk ; all the
other lymph vessels, including those which come from the intestines
(known as lacteals, because during the absorption of the digestive
products of alimentation they conduct the chyle, which has a milky
aspect), lead into the thoracic duct.

In this union of the lymphatics into ever-widening channels,
their diameter does not increase as rapidly as that of the veins :
moreover, they often form plexuses which anastomose among
themselves ; while, lastly, they enter all along their course into
special relations with the so-called lymphatic glands which, from
a schematic point of view, may be considered as analogous in
structure to the rete mirabile of the blood-vessels, and which retard
the flow of the lymph along the vessels that conduct it.

(6) The lymph capillaries are simpler in structure than the
lymphatic vessels properly so-called. They consist of a simple
membranous coat, the exceedingly delicate structure of which
when stained with silver
nitrate, shows flat plates _^
with characteristic wavy
outlines interlacing one
with another (Fig. 239).
They have no valves, but w^ ..„

are usually larger in ^O?a /^ ^ ^>5^
calibre than the smallest

Of the lymphatics, and Fm.^ 239.— Epitheliokl ^platelets ^of lymphatic capillaries

distinctly larger than ^S^'8 intestine' treated with 8ilver nitrate>
the blood capillaries.

They are irregular in form, and anastomose among themselves so
as to form a species of network, with uneven meshes and very
varied form. This lymphatic rete, irregularly excavated from the
connective tissue which supports it, opens or communicates freely
with the lymph vessels, which, although smaller than the
capillaries, have a more regular course, are clothed with fusiform
epithelial cells of less sinuous outline, and are provided with
valves.

To form a clear conception of the difference in form, arrange-
ment, and proportions of the blood and the lymphatic capillary
network, Fig. 240, in which the two capillary retes are injected
with contrasting stains, may be studied.

From the physiological point of view it is important to note
the special relation of the lymphatics and the blood-vessels in
particular parts of the body, e.g. the central nervous system, the
parenchyma of the liver, the bone tissues. In these regions the
smallest arterial and venous blood-vessels are enveloped with
lymphatic sheaths, just as the heart is invested by the pericardium
and the viscera by the peritoneum (perivascular lymphatics, Fig.

508

PHYSIOLOGY

CHAP.

241). It can be shown by the method of double staining with
silver nitrate and carmine that there is a perivascular lymphatic
space between the peripheral layer of the sheath and that which
adheres to the surface of the blood-vessels ; that slender connecting
filaments or lamellae pass between the two layers ; that the wavy
epithelioid plaques of the external layer are continued on to the

FIG. 240. —Frog's interdigital membrane, with injected blood and lymph vessels. (Ranvier.)
ss. Network of blood capillaries ; II, network of lymph capillaries ; pp, pigment cells. Mag-
nification, 50 diameters. >.£

internal layer, and also invest the connecting lamellae. Where
the blood-vessels are much increased in size, they perforate the
lymphatic sheath, and the two kinds of vessels run distinct from,
but alongside, one another. In certain of the lower animals,

FIG. 241. — (Left.) Artery of frog's mesentery, enclosed in perivascular lymphatic, which is
stained with silver nitrate, to show the outlines of epithelioid cells. (Klein.)

Fio. 242. — (Right.) Aorta of tortoise, enclosed in large perivascular lymphatic. (Gegenbaur.)
Numerous filaments of connective tissue are seen, connecting the blood-vessel with the
lymphatic.

however, e.g. in the frog, the larger vessels are also surrounded by
lymphatic sheaths, as also the aorta in the tortoise (Figs. 241, 242).
Kusconi (1845) was the first to describe the perivascular lymphatic
sheath.

(c) Outside the lymph capillaries also, in every part of the
body, and more particularly where there is loose connective tissue,
a labyrinth of lacunae or interstices of the most varied forms

xiv THE LYMPH 509

and dimensions, which are generally known as lymphatic spaces,
because they are full of lymph, may be observed. Again, the
tissues devoid of blood-vessels, like the cornea and the cartilages,
are provided with minute lacunar canaliculi, to which the
lymphatic humour necessary to cell nutrition penetrates. These
parenchymatous lymph spaces cannot be considered as lymph
capillaries, because they are not invested with the characteristic
epithelioid lining, which forms the true wall of the latter. They
represent a diffuse system of lacunae, interstitial to the cells
of the various tissues, which, according to Bichat's doctrine, is
generally regarded as the origin of the vascular lymphatic system,
i.e. of that provided with characteristic walls. In many inver-
tebrates the lacunar system, which has no proper wall, is the only
one that co-exists with the blood vascular system ; so that we may
logically regard the lymphatic vascular system as a perfecting, a
canalisation or successive centralising, of the primary lacunar or
interstitial system (Milne Edwards).

We know that the lymph spaces communicate freely with the
lymph capillaries properly so-called, because a fluid stain such as
Prussian blue, when injected into the meshes of the subcutaneous
connective tissue by means of a syringe, penetrates to the interior
of the lymphatics, particularly if the oedematous swelling that
forms at the point of injection is compressed by the finger, so as
to increase the tension of the distended lacunar spaces and facilitate
the penetration of the coloured fluid -by the natural way of com-
munication with the lymphatics.

(d) Besides the minute parenchymatous lymph spaces and
sinuses, the lymphatic capillaries and vessels communicate freely
with the serous cavity of the peritoneum, pleura, pericardium,
tunica vaginalis of the testicles, sub-arachnoid spaces, chambers of
the eye, membranous labyrinth of the ear, etc. So that these
larger and smaller cavities, which normally contain lymphatic
effusions, are, with regard to the system of lymphatic vessels, in the
same relation as the minute parenchymatous lymph spaces. The
researches of Kecklinghausen, of Ludwig and Schweigger-Seydel,
of Dogiel, of Eanvier and others, have shown this theory, as
previously enunciated by Mascagni, to be correct. It is easy with
Prussian blue to inject the lymphatic rete of the centre of the
diaphragm in a rabbit recently killed by bleeding and hung head
downwards, on pouring the stain into the abdominal cavity of the
diaphragm and assisting its penetration to the lymphatic rete of
the tendinous centre by means of artificial respiration with the
bellows (Fig. 243). On treating the excised diaphragm of a rabbit
with silver nitrate (1 in 300), the impregnation of the tendinous tissue
and epithelioid investment of the two faces, pleural and peritoneal,
reveals its structure and special disposition. On the pleural
surface the system of lymphatic vessels is shown in the form of

510

PHYSIOLOGY

CHAP.

arborisations with anastomosing trunks, the extreme branches of
which form parallel canaliculi, corresponding to intertendinous
clefts (Fig. 244).

The black lines of intercellular impregnation are clearer and
more delicate on the peritoneal face where there are large polygonal
cells, with here and there small islands of lesser and rounded cells ;
these are the lymph cells which invest the orifice and walls of the
small canals that bring the peritoneal cavity into direct communi-
cation with the lymphatic rete of the tendinous centre (Fig. 245).

Fio. 243.— Rabbit's diaphragm, viewed from abdominal surface, with lymphatic rete injected with
Prussian blue. (C. Ludwig and Schweigger-Seydel.) The figure is somewhat reduced.

According to Kanvier there is no need to invoke the existence of
intercellular stomata to explain the ready penetration of coloured
fluids or solid particles from the peritoneal cavity to the lymphatic
plexus, since the small cells which occupy the orifices of the afore-
said canaliculi do not completely occlude them. Still the retro-
peritoneal membrane of the frog, which forms the wall of the
cisterna lymphatica major in these animals, has, according to
Schweigger-Seydel and Dogiel and Eanvier himself, true stomata
or apertures surrounded by epithelial cells which are somewhat
differentiated and communicate freely with the peritoneal cavity
(Fig. 246).

XIV

THE LYMPH

511

It is very probable that there is direct communication, similar
to that which has been described in detail for the peritoneal cavity
and lymphatic capillary network of the tendinous centre of the
diaphragm, in all the other serous cavities of the body. Bizzozero-

FIG. 244. — Central tendon of rabbit's diaphragm treated with silver nitrate, viewed from pleura!)
surface. (Ranvier.) I, I, Lymphatic vessels in form of clear spaces anastomosing with one
another, and united by almost parallel inter-tendinous clefts. Magnification of 20 diameters.

and Salvioli described the communicating canaliculi between the
lymphatic of the parietal pleura and the pleural cavity.

Other writers admit free communication, in the form of small

FIG. 245. — (Left.) Central tendon of rabbit's diaphragm, treated with silver nitrate, seen from
peritoneal surface. (Ranvier.) /, Inter-tendinous lymphatic clelt; e, epithelioid investing
cells, forming at certain places along the lymph canaliculae islands of small, somewhat
granulated cells, which surround a stonia that is not always visible.

FIG. 246.— (Right.) Epithelioid platelet from frog's retroperitoneal membrane, treated with silver
nitrate, viewed from peritoneal surface. (Ranvier.) I, I, Intercellular lines of platelets which
surround an aperture or stonia .communicating with lymphatic canaliculi.

pores or canaliculi, with the lymphatic rete in the free walls of
certain mucosae, such as the bronchial and nasal mucosa. The
interstitial adenoid tissue of the lungs is rich in lymph canals,
which form a large irregular lymphatic meshwork round the
bronchi, pulmonary lobules and blood-vessels. When animals are

512 PHYSIOLOGY

CHAP.

made to breathe pigmented fluids by means of a spray, the
pigments penetrate by tiny pores through the epithelial cells of
the mucosa (Klein).

This theory is reinforced by the extraordinary rate at which
fluids and also blood are absorbed when injected into the trachea
of living animals. Nothnagel found blood -corpuscles in the
interstitial lymph spaces of the lungs barely 3-5 minutes after
injection.

II. The lymph contained in the lymphatic system, as briefly
described above, comes from three different sources : —

(a) The blood, which, by the network of blood capillaries to
the various tissues, constantly pours into the lymph spaces the
materials required for the nutrition of the tissue cells.

(ft) The living elements of the tissues, which continually give
off to the same system, both the products of their synthetic or
anabolic processes, destined for use by other tissues and organs,
and the products of their analytic or katabolic processes, destined
to be eliminated from the body.

(c) The food-stuffs • introduced, and more or less' modified or
digested in the alimentary canal, known as a whole by the name
of chyle, which is periodically absorbed by the lymphatic roots of
the intestinal villi. On the strength of this threefold origin we
may theoretically distinguish between blood lymph, tissue lymph,
and lymph of the digestive apparatus or chyle. Leaving aside for
the moment the chyle, the formation and absorption of which will
be discussed elsewhere, we will consider the constituents of lymph
properly so-called (of the blood and tissues), which is constantly
being formed and poured out into the lymphatic lacunar spaces.
Since the demand for nutritive materials in the different tissues
and organs is quantitatively and qualitatively very different, and
since, on the other hand, each tissue and organ is the seat of
specific anabolic and katabolic processes, it follows necessarily that
the lymph in the lacunar system of the different organs must
differ in consistency and composition.

Up to the present, however, we possess very few analytical
data in regard to the differences presented by the lymph coming
from the different organs, nearly all these differences being much
attenuated, or even obliterated, in the lymph collected from the
larger vessels, into which alone it is possible to introduce a
cannula. In examining the general characters and chemical
composition of lymph, it is almost always collected, as it flows,
from a cannula introduced into the thoracic duct of a fasting dog,
which yields the whole of the chemical constituents from tl
several lymphs (coming by the lymphatic channels to the different
tissues of the organs) that have not been consumed by the tissues,
nor absorbed by the blood-vessels. In collecting lymph from
animals of small bulk (rabbits, cats, etc.) the thoracic fistul

xiv THE LYMPH 513

(direct method) may be replaced by an indirect method, i.e. the
fistula of the jugular or, as Jappelli advises, of the subclavian.

The lymph which flows from the fistula of the thoracic duct is
a watery, slightly opalescent fluid, with a specific weight of 1012-
1022, less viscous than blood; when left to itself it coagulates
slowly, forming a more tenuous and less copious fibrin reticulum
than that which forms in the blood. A small quantity of peptone
injected into the veins makes it incoagulable, although the blood
remains coagulable (Shore).

When examined under the microscope it presents a certain
number of leucocytes precisely similar to those of the blood,
varying in size from 5 /x to 10 /x. The smaller and younger
leucocytes predominate in the lymph, the larger and adult
specimens in the blood; but the total quantity contained in
1 c.rnm. of lymph, though it varies considerably in different
animals and in the same animal under different circumstances,
seems not far removed from that of the leucocytes in the blood.

A certain number of erythrocytes are also constantly present
in lymph, even when precautions are taken to avoid any admixture
with blood, or when the lymph which is moving through the
lymphatics of a living animal is examined. The lymph being
almost or wholly deprived of oxygen, the erythrocytes give a
brownish colour to the fluid ; but on contact with air, owing to
the transformation of the haemoglobin into oxyhaemoglobin, they
assume a clear red hue, which tinges "the surface of the clot. It
is probable that some of these are not formed locally, but come
by diapedesis from the blood capillaries. So far as is known
at present there are no blood-platelets in lymph (Chap. IV. 9,
p. 118).

The plasma ot lymph contains all the essential constituents of
blood plasma ; but the quantitative relations are a little different.
In particular it has been pointed out that lymph plasma, as
compared with that of blood, is poor in protein, which has been
partly absorbed by the tissues ; on the other hand, it is richer in
water and alkaline salts, so that its reaction is generally more
alkaline than that of blood plasma. For the rest, the chemical
composition of lymph varies considerably. According to the most
reliable of the existing analyses, the percentage quantity of water
varies from 93'5-95'S ; the total solid residue is much less than
that of blood, varying from 4*2-6'5 ; the protein varies from 3*5-
4'3, fibrin from 0'04-0'06 ; generally speaking, the protein content
diminishes owing to the muscular movements, and increases in
proportion with rest and sleep. The neutral fats, soaps, cholesterin
and lecithin are scanty in lymph (0'4-0'9 per cent); when it
sometimes looks turbid and highly opalescent this is due not to
fats but to protein compounds in a special state of aggregation.
It also contains a small quantity of sugar (dextrose). Some

VOL. I 2 L

514 PHYSIOLOGY CHAP,

observers have also found a considerable amount of urea. The
ash of lymph, like that of blood serum, oscillates from 07-0 '8 per
cent, and contains an excessive amount of sodium chloride, from
the lymph flowing from the thoracic duct in dog. Hammarsteii
was unable to extract more than traces of oxygen and 37-53 per
cent of carbonic acid, i.e. a quantity greater than that contained
in arterial and less than that which can be extracted from venous
blood.

This last fact shows that part of the carbonic acid developed
by the tissues is directly absorbed by the blood capillaries and
veins, both in the lymph spaces and in the lymph capillaries. So,
too, we must remember that many of the solid products of the
tissues are directly absorbed by the blood-vessels, and that the
lymph contains only such substances turned out by the blood as
are not taken up by the tissues (blood-lymph) and such products
of the tissues as are not directly absorbed by the blood-vessels
(tissue-lymph). The lymph spaces and capillaries thus represent
an internal medium in which the reciprocal exchange of materials
between blood and tissues takes place ; and the lymph vessels,
properly so-called, represent a drainage system which slowly, by
long and circuitous paths, reconducts all the residual matters, both
from blood- and tissue-lymph, left over from the direct exchanges
in the lymph spaces and capillaries, to the circulatory torrent. In
view of this it is evident that the quantity of lymph that flows
through the thoracic duct in the time-unit cannot be taken as a
measure of the total amount of lymph poured into the blood day
by day. According to Heidenhain, the average amount of lymph
flowing in 24 hours from the thoracic duct of a dog that weighs
10 kgrms. is about 640 c.c. Noel Paton, from the thoracic duct of
a patient who weighed 60 kgrms., obtained about 1 c.c. of lymph
per minute, i.e. 1440 c.c. in 24 hours. From a woman, Munk and
Eosenstein obtained a quantity varying between 1200 and 2280
c.c. per diem.

It is possible also to collect lymph from different parts of the
body by introducing a small cannula into the larger lymphatic
trunks of the upper and lower limbs, the liver, and the intestine.
The lymph from the limbs is similar to that flowing from the
thoracic duct of a fasting animal, but it contains a smaller amount
of solids (2-4 per cent). On the other hand, the lymph from the
liver contains more solids (6-7 per cent), even in the fasting
animal. That coming from the intestine during inanition exhibits
an amount of solids intermediate to the above. For the rest, both
the composition and the quantity of these various lymphs differ
considerably according to circumstances, especially in regard to
the degree of functional activity in the tissues and organs whence
they are taken.

The large serous cavities of the peritoneum, pleura, peri-

xiv THE LYMPH 515

€ardium, tuiiica vaginalis of testicles, etc., normally contain only
a small quantity of lymphatic effusion, sufficient to lubricate
the walls. But under abnormal conditions, particularly with
mechanical obstruction of the venous circulation, and with marked
delay in the circulation, however produced, it is possible to collect
large quantities of fluid from these cavities, which differs con-
siderably in composition from the lymph obtained from the
thoracic duct. It has a low specific gravity (1008-1015) ; contains
a minimum amount of proteins (2'2-7'3 per cent) ; is almost
free of corpuscles : does not, generally speaking, coagulate spon-
taneously, but since it contains fibrinogen, coagulates on the addi-
tion of thrombin, or fluids which contain it (see Chap. V. 6).

Bainbridge, Asher, Mendel and Hooker noted that, under
given experimental conditions, the flow of lymph from the
cannula inserted in the thoracic duct continues for a not
inconsiderable time after death. Jappelli and D' Errico have
recently demonstrated that a post-mortem flow of lymph occurs
in every case, but is especially persistent when the death of
the animal occurs instantaneously (electrocution) and without
haemorrhage. According to the same authors small quantities of
post-mortem lymph are constantly obtained from the cervical and
brachial trunks as well. It is, however, mainly, though not
exclusively, visceral in origin.

Post-mortem lymph differs essentially in its characteristics from
the normal by : —

(a) Its osmotic pressure, which gradually increases up to and
beyond that of normal blood ;

(V) Its gradually decreasing electrical conductivity ;

(c) Its increased viscosity and greater content of solids ;

(d) Peculiar changes in the velocity of outflow ;

(e) Its appearance, now more haematoid, now more chylous,
always more turbid.

These researches of D' Errico and Jappelli show plainly that
post-mortem lymph is not pre-formed lymph. Hence it becomes
necessary to admit that the processes of lymphagenesis, whatever
these may be, continue for some time after death. Nor should
this be surprising when we reflect that after somatic death there
is no instantaneous abolition of all the haemodynaniic, osmotic,
cellular, and other factors which are invoked in explaining the
formation of lymph in the living animal.

III. The lymph contained in the lymphatic system is in
continual movement from the roots to the large trunks, like the
blood in the veins into which these empty themselves. This is
proved by the fact that ligation of a lymphatic trunk produces
filling and swelling below and comparative evacuation above, as
in the veins ; and that the valves in the lymphatics as in
the . veins impede the centrifugal course of the fluids within

516 PHYSIOLOGY CHAP,

them. With direct microscopic observation of the mesenteric
lymphatics of small mammals, again, it is possible to follow the
slow centripetal movements of the lymph by the motion of tl>e
leucocytes which it contains.

In this movement of the lymph, as in the analogous case of
the blood, we have to determine the mechanical factors by which
it is produced, its velocity and pressure, and its variations under
given conditions.

It is a fact that the lymphatic vessels are under a certain
degree of tension, i.e. they support a certain amount of pressure
which dilates them (Ludwig and Noll). In a lymphatic of the
horse's neck, the pressure is 10-20 mm. of water (Weiss).
Since fluids moving in a tube always proceed from higher to lower
pressure, we must assume (even if it cannot be directly proved)
that the pressure is maximal at the roots of the lymphatics ; that
it gradually falls from the branches to the lymphatic vessels ; that,
lastly, it is minimal at the point at which the thoracic duct opens
into the left subckvian, and the right lymphatic trunk into
the right subclavian. A priori the velocity of movement of
the lymph should decrease from the greater trunks to the more
peripheral branches in proportion as the area of the current-
bed widens. Experimentally, however, it is found that even in
the larger lymphatic vessels, e.g. the lymphatic trunk of the
horse's neck, the velocity of movement is very low ; according to
Weiss it equals 250-300 mm. per minute.

What is the origin of the vis a tergo which produces the
centripetal movement of the lymph, and is sufficient in man to-
overcome the force of gravity from the extreme end of the lower
limbs to the height of the venous vessels of the neck ? In the frog
and other amphibia, reptiles and fishes, the lymph hearts which
beat rhythmically, and which, by their muscular structure and
function, present many analogies with the blood heart, are
undoubtedly of great importance to the lymph flow. The frog is
provided with four lymph hearts : the two (posterior) sacral hearts
situated at the sides of the coccyx, being covered only by a delicate
aponeurosis and by the skin, can be seen beating even before they
are dissected ; the two (anterior) axillary hearts are covered by the
scapula. The sacral hearts carry away the lymph from the
lymphatics that accompany the sciatic vein ; the axillary hearts
that of the vessels coming from the head and anterior limbs.
In other amphibia, reptiles and fishes, there are only two lymph
hearts. Without entering into their mode of functioning, we
can see that since the frog is poorly provided with regular
lymphatic vessels, and in compensation has a copious supply of
large sinuses and lymph sacs, the four hearts represent so many
pumps necessary for promoting the flow of lymph from the said
sacs and sinuses.

XIV

THE LYMPH

517

I!

There are no lymph hearts in man and other mammals ; the
walls of the lymph vessels are, however, provided (as above stated)
with muscular elements, which interlace above the valves in
various directions (Fig. 238) in such a c<s
manner as to suggest that they may, by „

their rhythmical contraction, function as
minute hearts (Foster). No direct observa-
tions exist to confirm this theory. On the
other hand, there are certain data which
in'dicate that some of the lymphatic vessels,
under given conditions, are capable of rhythm-
ical and peristaltic contractions and dilata-
tions in the direction of the current. Arnold
Heller observed under the microscope, in the
mesentery of a guinea-pig anaesthetised with
chloral hydrate, that the lymphatics succes-
sively contracted and relaxed (on an average
six times a minute) in the peristaltic direc-
tion from the periphery to the centre. This
observation is unsupported, and, generally
speaking, it must be held that the muscle cells
of the lymphatic walls behave passively, like
those of the blood-vessels, in regard to the
normal lymph current.

Pursuing the line of strict analogy be-
tween blood-vessels and lymphatics, it may
also be stated that the muscle cells of the
lymphatics have an automatically oscillating
tonus, which may be modified or regulated
by the influence of special vascular nerves.
The recent work of Gley and Camus (1894-
1895) has made it possible, in the physiology
of the lymphatic vessels, to define accurately
certain fundamental ideas as to the dilator
and constrictor functions of the nerves which
influence the muscle cells of the receptaculum
chyli and the thoracic duct. After success-
fully overcoming some serious technical diffi-
culties, these two experimenters succeeded
in registering on dogs the pressure in the
receptaculum, when reduced to a closed
cavity, communicating below by a cannula

with a receiver filled with physiological saline, kept at low and
constant pressure ; above, it communicated by a second cannula
inserted into the thoracic duct with a small water manometer,
provided with a float and a lever writing on a smoked cylinder.
Fig. 247 gives a clear idea of the method.

VOL. I 2 L a

If
Is

eg

518 PHYSIOLOGY

CHAP.

The results arrived at by Gley and Camus can be summed up
in a few words : —

(a) The left splanchnic nerve contains dilator fibres and also
constrictor fibres to the receptaculum. As the electrical excitation
of the nerve trunk almost always produces depressor effects, we
must conclude either that the constrictor fibres are not very
numerous in the part of the nerve which is stimulated, or that
they are much less excitable than the dilator fibres.

(b) The motor nerves to the thoracic duct run in the thoracic
part of the sympathetic chain. Here also there are dilator and
constrictor fibres, and the activity of the former outweighs that of
the latter.

(c) It is also possible, retiexly, by exciting a sensory nerve to
determine dilator effects upon the receptaculum and thoracic
duct. If, e.g., one sciatic is ligatured, alternate constriction and
dilatation will be observed in place of the former constant tonus.
On exciting the central end of a divided sciatic, there is invariably
a dilator effect.. On the other hand, asphyxia on cessation of
artificial respiration determines contraction of the thoracic duct
similar to that exhibited by the stomach, bladder, uterus, bile
duct, etc.

These observations show the importance of the muscle cells
and motor nerves of the lymphatic vessels, in so far as they are
capable of altering their lumen, and can thus facilitate or hinder the
centripetal movement of the lymph. If these active vascular
movements were more energetic, rhythmical, and peristaltic or
progressive from the branches to the lymphatic trunks, it is
evident — in view of the function of the many valves with which
the lymphatic system is furnished — that they would have the
same effect as the heart-beats, and would represent a form of
propulsion adequate to account for the lymphatic circulation.
But this view has no experimental basis, nor does it harmonise
with the theory of the venous circulation, which depends essentially
upon the vis a tergo developed by the cardiac rhythm.

According to Ludwig the lymphatic circulation depends
essentially on the vis a tergo due to the pressure on the lymph
that fills the pareuchymatous lymph spaces, which in its turn
depends on the pressure under which the blood circulates in the
capillaries. Thus the lymph circulation is also, in last resort, the
effect of the force of the heart. The lymph represents a transudate
from the blood through the fine membrane constituted by the
capillary walls, by a process of filtration which depends on the
difference of pressure between the blood circulating in the
capillaries and the lymph poured out into the spaces. This theory
will be analysed below. For the moment it is enough to say that
it is correct, in so far as it assumes the lymph circulation to be
due to the vis a tergo caused by the pressure on the lymph in the

xiv THE LYMPH 519

lacunar system ; but it is inadequate, in so far as it holds the lymph
to be merely a product of simple nitration. The pumping of the
heart promotes the flow of lymph, not merely by favouring
filtration through the capillaries, but by another simpler mechanism.
At each systolic efflux the whole arterial tree is dilated by the
passage of the pulse wave, in consequence of which the whole of
the perivascular lymphatics immediately receive an impulse to
centripetal evacuation of the lymph which they contain. Since
it is shown from plethysmographic observations that the total
volume of the body is increased at each beat transmitted from the
heart, it may logically be admitted that the lymphatics which run
separate from, and independent of, the blood-vessels must, at each
pulsation of the arteries, be sensible of a pressor effect which
favours the movement of the lymph.

More important, however, and certainly better demonstrated,
is the influence exerted on the lymph circulation by the active
and passive movements of the skeletal muscles. If a cannula is
introduced into the principal lymphatic vessel from the lower
extremity of a large dog, no flow of lymph will be perceived so
long as the muscles of the limb are relaxed and motionless. As
soon, however, as active movements are excited in the limb, or
alternate passive movements of flexion and extension are performed
on it, the flow of lymph through the cannula becomes suddenly
active. This fact shows that the muscular movements compress
the lymphatics and empty them in the centripetal direction,
because the valves prevent movement of the lymph, as of venous
blood, in a centrifugal direction. The rise of the lymph in the
lower limbs is principally effected by this mechanism.

On the other hand, the respiratory mechanism exerts a
preponderating influence on the movements of the lymph in the
visceral lymphatics. The lymphatic, like the venous, current is
continuously affected by the normally negative pressure of the
thorax, by which the lymph is aspirated, like the venous blood,
from the extrathoracic to the intrathoracic vessels. This negative
thoracic pressure increases during inspiration, and the positive
abdominal pressure increases during active expiration. These
two factors accelerate the flow of lymph, particularly in the
visceral lymphatics and thoracic duct, and propel it to the
mouths of the two subclavian veins, where it mixes with the venous
blood.

IV. The exact determination of the mechanism which effects
the formation of lymph is one of the most complex problems
in physiology, and has been much .discussed of late years since
Heidenhaiii (1891) opposed to the mechanical theory of filtration
(a relic of the ancient doctrine of Bartholin and Mascagni, to
which Ludwig and his School endeavoured to give an experimental
basis) his secretory theory, in which he asserts that the formation

VOL. I 2 L I

520 PHYSIOLOGY CHAP.

of lymph is essentially the effect of the activity of the living
cells which form the walls of the blood capillaries. For better
orientation in this difficult and complex subject we will tabulate
the different groups of facts brought forward and consider them
separately.

A consensus of experimental results shows that increased
pressure in the blood capillaries is followed by increased formation
of lymph :—

(a) We know from the works of Emminghaus that the
occlusion of the veins in one limb not only increases the current
flowing through the cannula inserted into the lymphatic of that
limb, but considerably modifies the constitution of the lymph, so
that it becomes richer in erythrocytes and poorer in dissolved
solids. This fact is in agreement with clinical observation, which
shows that in cardiac failure, hepatic cirrhosis, thrombosis of the
veins, and in fact in every case in which there is obstruction or
local interruption to the venous circulation, with consequent
increase of pressure in the capillaries, the lymph transudes through
these so freely that oedema, i.e. stagnation or accumulation of
lymph in the tissue spaces, results.

(b) Both Heidenhain and Starling obtained the same results
as Emminghaus after ligaturing the portal vein in the dog. The
marked rise of intra-capillary pressure in the intestine increased
the flow of lymph from the cannula in the thoracic duct four to
five times, with diminution of colloids and increase of red blood-
corpuscles.

(c) On obstructing the vena cava inferior above the diaphragm
there is a marked fall of arterial pressure, in consequence of which
the viscera become anaemic, while there is still an acceleration of
lymph-flow greater than that which occurs after ligation of the
portal vein. The lymph does not contain more blood, but
becomes richer in solids, while at the same time clearer and
less coagulable. These results of Heidenhain were controlled by
Starling, who demonstrated that in the above experiments the
lymph was derived from the lymphatics of the liver and not of the
intestines, as Heidenhain believed. In fact, after the occlusion of
the vena cava, pressure increased below the point where the block
occurred, producing a corresponding rise of pressure in the hepatic
capillaries ; on the other hand, the pressure in the portal vein
diminished (as known by the blanching of the intestines) in conse-
quence of the marked fall of aortic pressure.

(d) On occluding the thoracic aorta (by introducing from the
right carotid a catheter ending in a rubber balloon which could
be inflated by the injection of water), Heidenhain observed that
arterial pressure below the point obstructed could fall to zero,
while the lymph current might continue for 1 to 2 hours longer,
although with diminished velocity and progressive reduction.

xiv THE LYMPH 521

The composition of the lymph also changed, since it became turbid . j

and whitish, not from increase in the fats and leucocytes, but / /

owing to a kind of partial precipitation of the proteins. This

turbidity does not always persist ; sometimes it ceases after 15 to

30 minutes. In any case the percentage content of solids in the

lymph increases, even after it has become clear. Lastly, the lymph,

while of greater density, becomes less coagulable during the

occlusion of the aorta. On repeating this experiment Starling

saw that the pressure in the inferior vena cava is not altered, and

may even rise slightly under the conditions described, while that in

the aortic system is greatly reduced. The lymph that continues

to flow after the occlusion of the aorta can therefore only come

from the lymphatics of the liver. Indeed, on ligaturing the latter,

he found that the entire ilow of lymph from the thoracic duct was

arrested.

According to Heidenhain these phenomena cannot all be
interpreted on the mechanical theory of nitration ; according to
Starling, on the other hand, since they demonstrate that the
increase of lymph flow is invariably associated with a correspond-
ing increase of pressure in certain capillary regions, they ar&
cogent arguments for the importance of nitration in the formation
of lymph. The various changes in constitution arid concentration
presented -by the lymph from the different regions have still,
however, to be explained.

It will be observed that in all the •experiments referred to, the
increase of pressure in the blood capillaries is due to a block in
the venous circulation, which is accompanied either by abnormal
retardation or by venous stasis. This fact never occurs under
physiological conditions. It may be conjectured that the walls of
the blood-vessels are altered by the long stagnation of the venous
blood, that they become more permeable, more sensitive to changes
in pressor effects, and permit an abnormal nitration of lymph, to
which they do not lend themselves under normal conditions. We
cannot, therefore, from these facts deduce a physiological theory of
the normal formation of lymph by a process of simple filtration.
Physiologically, capillary pressure only varies in consequence of
slow oscillations in tone of the small arteries, which are provided
with strong muscles. When these dilate, capillary pressure rises,.
because, owing to diminished resistance, a larger amount of the
impulsive force of the heart is transmitted to the capillaries ; but,
in addition to the rise of pressure, the velocity of circulation
through the capillary network rises also, so that its walls are
bathed in a blood that undergoes rapid and constant renewal. In
order to establish the significance of filtration in the formation of
lymph under physiological conditions, it must also be shown that a
simple rise in arterial and capillary pressure, with unimpeded
venous flow, constantly produces increase in the lymphatic

522 PHYSIOLOGY CHAP.

current. The following are the facts which bear upon this pro-
position : —

(a) When in a dog all the cervical and brachial nerves to an
anterior limb are divided so as to paralyse all motor nerves to the
muscles as well as the vessels, and the cervical cord is stimulated
electrically so as to produce contraction of all the vessels of the
body except those of this limb, there is necessarily a marked efflux
•of blood with increased arterial and capillary pressure in all the
vessels of the paralysed limb. Nevertheless the quantity of lymph
flowing with the aid of the passive, rhythmical movements of the
limb from the cannula inserted into its lymphatic trunk does not
show the slightest augmentation, but rather tends to diminish
gradually, as it did previous to stimulation of the spinal cord
(Ludwig and Paschutin).

(6) When the so-called chorda tympani is excited there is a
conspicuous dilatation of the small arteries of the submaxillary
gland, associated with increase of pressure and acceleration of
the blood-flow through the capillaries (Chap. X. 1, p. 341). These
effects are certainly associated with increased formation of lymph,
which pours into the glandular lymphatic spaces, and (as we
shall see, Vol. II. Chap. II.) is immediately utilised by the gland
cells for the formation of an abundant salivary secretion
(Ludwig), so that it does not accumulate in the glandular
lymphatics. If, before exciting the chorda tympani, the animal is
slightly atropinised, the vessels of the gland will equally dilate,
and capillary pressure rises as before ; but the salivary secretion
does not occur, nor is there any increased formation of lymph,
since it does not accumulate in the connective- tissue spaces of the
gland, nor does the flow of lymph from the glandular lymphatics
increase (Heidenhain). To interpret this effect we must remember
that atropine paralyses the activity of the secretory nerves, leaving
the vasodilator fibres of the chorda tympani untouched. Mere
arterial dilatation and rise of pressure and circulatory velocity in
the capillaries of the gland are not enough to provoke increased
formation of lymph, such as does, on the other hand, occur
when the secretory activity of the gland cells are excited.

These facts are obviously irreconcilable with the theory that a
primary importance must be assigned to the mechanical process of
filtration in the physiological formation of lymph. They prove
that when the increased pressure in the blood capillaries is
associated with acceleration, instead of with slowing or stasis of
the circulatory current, no increased formation of lymph takes
place.

Another important series of experimental observations shows
that the lymph current may increase conspicuously, independent
of any marked rise in pressure in the blood capillaries :—

(a) Certain chemical substances, when injected into the blood,

XIV

THE LYMPH 523

induce a considerable increase in the formation of lymph, and
were therefore termed lymphagogues by Heidenhain. Such are
commercial peptone, extracts of crab's muscle, of the head or body
of leeches, the body of river mussels, the intestine or liver of dog,
egg albumin, curare, and (according to D' Errico) gelatin. All
these substances produce the same effect as regards flow of lymph
from the thoracic duct : immediately after the injection of the
lymphagogue into the vein, the lymph current increases as much
as four times, and the effect may last for over an hour. The
lymph becomes richer in proteins ; it subsequently becomes turbid,
then clears again : its coagulability diminishes or disappears.
This increase in the lymphatic current coincides with a slight fall
of arterial pressure, associated with acceleration of cardiac rhythm.
Starling holds that under these conditions also the lymph derives
principally from the liver, and is therefore more concentrated ; and
that if the portal lymphatics are ligatured there is no longer any
lymphagogic action after injection. Pugliese, however, has shown
that extract of crab's muscle and curare produce a marked increase
of lymph in the front limb of the dog as well, with a sensible
increase in its content of solids. Increased lymph formation
cannot therefore be considered as a phenomenon localised in
the hepatic capillaries.

(&) As against these lymphagogues which increase the lymph
that is derived from the Uood Heidenhain ranges a second class of
substances, which are lymphagogues * because they increase the
lymph that comes from the tissues. Such are sugar, urea, sodium
chloride, and other crystalloid substances when injected in
sufficient quantities into the blood. They soon leave the blood,
abstracting large quantities of water from the tissues, which is
partly reabsorbed by the blood, partly goes to swell the lymphatic
current. The flow is accelerated ; the lymph becomes momentarily
turbid, and is reddish ; presently it coagulates slowly, although it
contains many crystalloids ; it is conspicuously poor in colloids.
The composition of the blood changes in consequence ; the water
increases, and the relative quantity of erythrocytes and haemo-
globin is lessened. The increase in the lymph stream is usually
associated with a slight rise of arterial pressure, proportionate in
each case to the quantity of lymph produced.

The lymphagogues of the second series accordingly produce
changes in the blood and lymph of an opposite character to those
observed with lymphagogues of the first series. Their antagonistic
action is also shown by the fact that the latter do not excite
urinary secretion, while the former do,, so that the acceleration of
the lymph stream is parallel to the excretion of urine.

V. These facts, as demonstrated by Heidenhain, were confirmed
by successive experimenters ; but they have given rise to various
interpretations. Heidenhain made them the basis of his secretory

524 PHYSIOLOGY CHAP.

theory. Cohnheim had already on several occasions expressed the
idea that the vessel walls must be something more than a simple
passive filter. Following out this idea, Heidenhain affirmed that
the lymphagogic effects of the double series of substances above
indicated should be considered as proving that the epithelioid
cells which constitute the walls of the blood capillaries are to be
considered as secretory cells analogous to gland cells, capable, i.e.,
of separating certain substances from the blood, and of pouring
them into the system of lymph spaces with a brisk displacement
of water, to provide for the various and specific nutritive needs of
the different tissues and organs. Heidenhain alleges that certain
secretory organs, such as the udder of the milch cow, are capable
of yielding 25 litres of milkier diem, containing 42 '5 grms. of lime.
Since the lymph poured into the thoracic duct does not contain
more than O1S per thousand grams, 236 litres of lymph would
be required to provide the gland cells with all the lime needed for
the production of the milk, on the hypothesis that they derive all
the materials required for their function from the lymph as such.
If, on the other hand, we assume secretory activity on the part of
the cells forming the capillary walls, it is easy to explain how, with
slight translocation of water, they are able to supply the gland with
all the material required. Seeing that each organ or tissue must
obtain its specific nutritive materials from the lymph, it is assumed
that they pour out specific products into the lymph, which excite
the secretory activity of the capillary walls, and thus provoke
secretion of those substances which the organ requires.

It cannot be denied that this theory of Heidenhain is a very
bold one. Not because (as one of our younger physiologists main-
tains) it diverges from the principle of the mechanical interpretation
of functional processes — the admission of one secretion within the
body more or less could not sensibly modify the general trend
of science ; but because Heidenhain, prior to formulating his
secretory theory, did not examine fundamentally to what point
the process of lymph formation could be interpreted by the aid of
the physical laws at present known to us.

To the secretory theory, W. Cohnstein, in a series of interest-
ing papers (1893-1896), opposes what he terms the transudation
theory, according to which the formation of lymph is due to two
well-determined physical processes : filtration, which depends on
the difference of pressure between the two liquids separated by a
permeable membrane, represented by the capillary walls ; and
diffusion, due to the different chemical constitution of the two
fluids. The lymph contained in the extra - capillary lymph
spaces is during life the subject of continuous changes, pro-
duced by the metabolic activity of the parenchymal cells, which
draw from it the substances required for their nutrition, and
pour out the progressive and retrogressive products of their

xiv THE LYMPH 525

elaboration. Accordingly, chemical differences between the lymph
and the blood plasma of the capillaries are constantly arising, and
promote a continuous diffusion current from the blood to the
lymph. In the above example of the mammary gland it is con-
ceivable that its secretory epithelia, by constantly subtracting
lime from the lymph, set up a persistent diffusion current, by
which fresh lime passes continually from the blood to the lymph
by way of the capillary walls. That this diffusion current may
be rapid enough to provide for the chemical needs of the several
tissues will be readily understood on considering the extra-
ordinary rapidity of respiratory gas exchanges, arterial being
transformed into venous blood in the time during which the
capillaries are traversed. Cohnstein also quotes the researches of
v. Brasol (1884) and of Klikowicz (1886), which prove that sugar
and salts injected into the blood in concentrated solutions pass in
a few moments from the blood to the tissues, and thence drive out
into the blood such quantities of fluid as considerably to increase
the blood pressure and diminish the relative quantity of haemo-
globin from 30-60 per cent. These facts show that simple processes
of diffusion in the body can sufficiently account for the rapid
transport of considerable quantities of solid matters from the
blood to the tissues. Undoubtedly the same may occur in the
normal formation of lymph when diffusion is aided by filtration.

There .is no necessity to resort to any mechanism other than
that of diffusion and filtration to explain the effects of the
lymphagogues of Heidenhain's second category. Since these
increase the concentration of the blood, much water passes from
the tissues into the blood to re-establish iso-tonicity, or equilibrium
of osmotic pressure, which raises the pressure in the capillaries and
favours filtration, and therewith the lymph stream, along with
which the injected substance passes out of the blood. Heidenhain
observed that the lymphagogic action of crystalloids was pro-
portional to their power of attracting water, which again, accord-
ing to v. Limbeck, is proportional to their diuretic action.

More controversy arises as to the interpretation of the effects
of lymphagogues of the first category. Since the increase in the
lymph current cannot be explained by a rise in intra-capillary
pressure, which, on the contrary, falls, Starling holds that these
substances, which are toxic to the heart, muscles, and leucocytes,
are also toxic to the epithelioid cells of the capillary walls, by
chemically -altering them and rendering them more permeable, so
that the normal pressure is sufficient to cause increased filtration.
Cohnstein, on the other hand, maintains that the lymphagogic
action of these substances must be interpreted as the effect of
diminution of the endosmotic equivalent of the blood, and conse-
quent diminution in the quantity of water that passes by diffusion
from .the lymph spaces into the blood capillaries. We know that

526 PHYSIOLOGY

CHAP.

peptone, extract of crab's muscle, etc., alter the composition of the
blood, making it more permeable and rendering it incoagulable ;
but Cohnstein has demonstrated experimentally that it undergoes
such modifications in its chemical constitution as to reduce its
endosuiotic equivalent very considerably, this being the reason
why the amount of lymph increases, and with it the lymphatic
current.

The doctrine of transudation (which results from a combina-
tion of the process of nitration with that of diffusion) is thus
adequate to explain all the phenomena of the formation of lymph
under various experimental conditions, and to render the
hypothesis of the secretory functions of the capillary cells super-
fluous. . Of course this theory does not exclude the possibility that
these cells may under abnormal conditions suffer chemical or
physical changes which induce modifications in the normal forma-
tion of lymph, since both nitration and diffusion are known to
depend upon the constitution of the permeable animal membranes.
In a word, it is not denied that the living cells of the capillary
walls are the seat of incessant changes corresponding with the
degree and kind of their metabolism. What is denied, as being
superfluous and non-proven, is that they fulfil a secretory function
properly so-called, and that the substances secreted from the blood
in the lymphatic spaces differ specifically according to the specific
needs of the several tissues and organs.

The latest work on this subject by Lazarus Barlow, Hamburger,
and Asher tends to show that the role of filtration in lympha-
genesis must be less than that of the osmotic processes (diffusion),
while the relative permeability of the cells of the individual tissues
is undoubtedly of importance (Ellinger). Asher and his pupils, in
particular, have studied the influence of the activity of cell
metabolism in the several tissues on the formation of lymph.

Another series of experimental observations, made recently by
Carlson, Greer, and Luckhardt (1907-10), is of some interest in the
problem of the mechanism of lymph formation. Here we can
only state briefly that in a large number of experiments (seventeen
horses and five dogs) the chloride content of the lymph was found
higher than that of the blood serum ; this statement is confirmed
by the fact that lymph is a better electrical conductor than serum.
A ten per cent increase in the NaCl content of a physiological
saline solution causes an increase in the electrical conductivity
which is comparable to the increased conductivity of the lymph
over the serum (Luckhardt). These facts do not agree with any
mechanical theory of lymph formation, whether the filtration or
the osmosis theory. According to the former, the quantitative
salt content of both lymph and serum ought to be the same ;
according to the latter it ought to be maintained constant.

Pugliese (1901) investigated the influence of the vasomotor

xiv THE LYMPH 527

centres on the formation of lymph. On cutting the medulla
oblongata, or blocking its blood -supply in dogs by means of
artificial emboli, he noted a rise in the amount, and fall in the
concentration, of the lymph flowing from the thoracic duct. Under
these conditions, also, the intravenous injection of curare, bile, and
urea determined an increase of lymph, which with the two first
substances becomes more concentrated, with urea, on the contrary,
less concentrated than the normal. Peptone in dogs with a
paralysed vasomotor centre exhibits a much less intense lympha-
gogic action than the normal. The lymphagogic action of caffein
disappears entirely, while sodium chloride preserves its action of
lymphagogic potency.

VI. All that we have been considering refers exclusively to
what Heidenhain calls blood-lymph. We must now examine the so-
called tissue-lymph, and the organs which more particularly concur
in forming and modifying it.

We have seen that lymph cannot be considered as a simple
residue of blood plasma, unappropriated by the tissue cells. Part,
at least, of the chemical products formed by these cells is poured
into the lymph spaces, and modifies and renders more complex
the lymph turned out of the blood capillaries. Theoretically, it is
undeniable that the lymph from different organs and tissues must
have a different composition. The work of Heidenhain, completed
and partly rectified by Starling, gives confirmatory evidence of
this. The lymph coming from the limbs regularly contains a
lower percentage of proteins than that from the intestine, and the
latter contains a larger amount of proteins than that from the
liver. It appears improbable that this difference depends — as
supposed by Starling — on the normal differences in permeability
of the blood capillaries in different areas. It is more logical to
admit that the three kinds of lymphs are dissimilar because, coming
from different tissues, they are modified in various ways by the
elaboration products of the same.

The quantity of lymph, again — as was justly observed by
Asher and Barbera — may and must depend on the degree of
functional activity of the tissue cells. When the work of an organ
increases, the quantity of dissimilation products increases also, and
with it the quantity of lymph poured into the lymphatic spaces ;
on the other hand, this increase in the products eliminated by the
organ may, since it modifies the difference in osmotic pressure
between blood and lymph, determine an increase in the transudation
of plasma through the blood capillaries. Experimental data in
support of this theory are not wanting. Stimulation of the lingual
branch of the trigeminus causes a marked accumulation of lymph,
with consequent oedema in the corresponding half of the tongue.
This phenomenon was first observed by Ostroumoff, and was
subsequently confirmed and developed by Marcacci (1883). It i&

528 PHYSIOLOGY CHAP.

only necessary to tetanise the lingual nerves for a long time, and
with brief interruptions, in order to produce conspicuous tumefac-
tion of the half of the tongue corresponding to the side stimulated,
associated with dilatation of the arterial and venous vessels.
Marcacci has shown that the effect depends principally upon the
pronounced formation and accumulation of lymph (oedema), rather
than on hyperaemia. After protracted tetanisation of the lingual
nerve, he saw not only that the lymphatics of the tongue dilated,
but also that a large lymphatic gland which is in direct relation
with them, and lies near the submaxillary gland, swelled and
increased in weight. Since, as has been seen, the rise of arterial
pressure is not of itself enough to determine any great increase of
filtration through the capillaries, we hold that the effect depends
on the extension of nerve influence in this case to the lymph-
forming elements of the lingual tissue, which, when excited, pour
a more copious flow of lymph into the lymphatic spaces. The same
thing is seen on exciting the chorda tympani, which innervates the
submaxillary gland, but with the difference that in this case the
lymph which is more abundantly formed does not, after transform-
ation into the saliva of the glandular cells, flow back into the
lymphatic system, but is canalised in the excretory ducts of the
gland.

All tissues that are in relation with the lymphatic system are
more or less lymphagenic in 'a wide sense, i.e. they pour into the
lymphatic system and thence into the blood system a part at least
of their elaboration or waste products, thereby contributing to the
formation of the lymph or modification of its composition. Among
these, more particularly, are the so-called lymphoid tissues in
general, the follicles and glands attached to the lymphatics, the
red bone-marrow, the thymus, and the spleen.

VII. Lymphoid (or Adenoid) Tissue is the name given to such
tissues as consist essentially of branching cells and fibres of
connective tissue which are so interconnected as to constitute a
network with very fine meshes, within which the leucocytes are
enclosed in great numbers. Diffuse in form, with no circumscribed
boundaries, the lymphoid tissue is found in the mucosa of the
respiratory passages, throughout the intestinal tract, in the marrow
of bones, etc. In the sharply-defined form of rounded nodules the
size of a small pin's head, lymphoid tissue appears in the so-called
solitary follicles, which are found in large numbers in the intestinal
mucosa, especially in its lower part. Each follicle consists of an
adenoid rete, with very fine and regular meshes, filled with leuco-
cytes. The meshes are larger, and the leucocytes less crowded, at
the centre and periphery of the nodule, as shown in Fig. 248. At
the surface, where the follicle projects into the intestine, the villi
are usually absent, and the crypts of Lieberkuhn are found at its
-circumference. One or more arterioles penetrate into the nodule,

XIV

THE LYMPH

529

and break up into a capillary network which subsequently reforms
into one or more venules. Kound the nodule there is a space or
lymphatic sinus filled with lymph, interrupted by afferent and
efferent blood-vessels and filaments of connective tissue, which
unite the tissue of the adenoid serosa with the surrounding
connective tissue. The lymph sinus and the blood-vessels and
connective-tissue bridges are clothed with epithelioid plates, as
shown by the silver nitrate reaction.

The leucocytes implanted in the adenoid rete are usually
smaller than those of the blood, owing to the paucity of protoplasm
around the nucleus. Many of them, lying within the central

PIG. 2-18. — Solitary follicle from large intestine of man. (Bnhm.) ep, Intestinal epithelium ;
pi, Lieberkiihn's crypt ; eg, germinal centre ; sm, sub-mucous tissue.

mass of the follicle, are in the stage of mitotic division, so that
Flemming gave the name of centrum germinativum to the mid-
point of the follicle, at which there is a continuous multiplication
of leucocytes. In proportion as new leucocytes are formed at the
centre, the adult leucocytes which lie at the peripheral part of
the follicle are driven towards the lymphatic sinus, where they
are caught up in the general lymph current. The vis a tergo that
drives them out of the meshes of the adenoid rete is no doubt
due to the lymph which transudes from the network of the
blood capillaries in the follicle, and increases the tissue tension.
The lymph which is thus formed, while it serves as food for the
leucocytes, is modified by the products of their metabolism. It is
probable that a proportion of these products passes by diffusion
into the interior of the blood-vessels, so that the blood, on
VOL. I 2 M

530 PHYSIOLOGY CHAP.

traversing the follicles, yields up some materials and acquires
others.

The so-called Peyer's Patches, of an oblong oval form, which
are found to the number of 20-30 in the small intestine (particu-
larly in the ileum), consist of groups of the solitary follicles, so
that they are also termed agminated follicles. Each patch in man
consists of 50-100 follicles, arranged in one plane, which lie
immediately beneath the intestinal epithelium, and dip down so
far into the submucosa that they interrupt the muscular layer.
From the physiological standpoint they differ in no essential from
the solitary follicles.

A more complex structure attaches to the lymphatic glands,
numerous and widely distributed bodies which lie along the

FIG. 249. — Vertical section of dog's lymphatic gland, the afferent lymphatics injected with Prussian
blue, stained with picrocarmine. (Klein.) c, Capsule, showing a lymph vessel cut trans-
versely, communicating with cortical sinuses ; a, lymph follicles of cortex surrounded by lymph
sinuses, and separated by trabeculae ; b, medullary portion of gland, showing' reticular
adenoid tissue and lymphatic sinuses injected with blue. Magnification of 25 diameters.

course of the lymphatic vessels. They differ in size, and are for
the most part bean-shaped or kidney- shaped, with a concavity
which is called the hilum of the lymphatic gland, whence issue
the efferent lymphatics, while the afferent vessels enter on the
convex side. The arterial and venous blood - vessels enter and
leave respectively at the hilum. Each ganglion is invested with
a capsule composed of two layers, the outer of which consists of
loose connective tissue, and the interior of more compact connective
tissue with numerous smooth muscle cells. From this internal
capsular layer septa, or trabeculae, of the same connective and
muscular character as the capsule, run out, and pass to the hilum,
where they divide the cortical part of the gland into various com-
partments known as alveoli. On joining the internal or medullary
part of the gland the trabecular tissue divides into finer
strands interconnecting in every direction, and forming an open

XIV

THE LYMPH

531

network which divides the medulla into a number of spaces, much
smaller than the alveoli, that communicate freely among themselves
to form a labyrinth. The capsule and cortical trabeculae and the
network of medullary septa make up the skeleton or supporting
tissue of the lymphatic gland (see Fig. 249).

Each alveolus of the cortex is occupied by adenoid tissue rich
in leucocytes, in structure very similar to a solitary follicle, and
therefore known as an alveolar follicle. This is separated from
the walls of the alveoli (represented by the capsule and trabeculae)
by a lymph sinus, which
merely differs from that
surrounding a solitary fol-
licle by the fact that its
lumen is traversed by a
larger amount of reticu-
lated tissue (Fig. 250). The
medullary spaces, too, are
occupied by follicular sub-
stance in the form of rami-
fied and anastomosing cords
known -as the medullary
cords. These also are sur-
rounded by lymph sinuses
throughout their course.
As the adenoid tissue of the
cortical follicles continues
in the medulla as the med-
ullary cords, so the circuin- Fl(
follicular lymph sinuses
continue in the spaces
which surround the medul-
lary cords. In the hiluni
of the gland the whole of
the lymph sinuses collect
into a terminal sinus, which

communicates with the efferent lymphatics. The afferent lymph-
atics, after forming a plexus between the two layers of the capsule,
communicate with the perifollicular lymph sinuses. Like the
lymph sinuses of the solitary follicle, those of the glands are
invested with epithelioid platelets as shown by the silver nitrate
reaction.

The small arteries which penetrate into the hiluni of the gland
ramify along the trabecular skeleton, here and there giving off
branches that traverse the sinuses and plunge into the adenoid
tissue, where they are resolved into a capillary network that
extends to the medullary cords and the follicles contained in the
alveoli. The small veins that arise from the capillary rete also

J. 250. — Cortical section of lymphatic gland of man.
through capsule, cortical sinus, and peripheral portion
of a follicle. Many of the lymphocytes have been
removed by the shaking. (Klein.) c, Capsule com-
posed of external fibrous stratum, and internal layer
of flat, nucleated corpuscles of connective tissue ;
x, circumfollicular lymph sinus, containing largo
meshed reticulum of ramilied connective-tissue cells ;
a, adenoid tissue of a follicle, composed of network
with finer and more compact meshes. Magnification,
350 diameters.

532 PHYSIOLOGY CHAP,

cross the sinuses and enter the trabeculae, leaving eventually by
the hilum.

The leucocytes which fill the meshes of the adenoid tissue,,
both of the follicles and of the medullary cords, differ in no way
from those of the solitary follicles of the intestine. The follicles
of the alveolar glands also show a germinative centre, where many
leucocytes are seen in process of mitotic division (Fig. 251).
Mitosis can also be seen in the medullary cords, though less
freely.

The preceding description of the functions of the solitary and

FH;. 251. — Alveolar follicle withladjacent medullary cord of a lymphatic gland, in man. (Bohm.)
/, Follicle ; cm, medullary cord ; cy, germinal centre, in which many leucocytes are seen
undergoing mitosis.

agminated follicles applies perfectly to the lymphatic glands as
well. We may regard the former as simple terminal lympha-
poietic organs, which are found sparsely disseminated at the roots
of the lymphatic system ; and the latter as complex lympha-
poietic organs, intercalated along the course of the lymphatic
vessels, and therefore, unlike the former, provided with afferent
and efferent vessels.

After the microscopic work that has been done on the lymphatic
glands under various physiological and pathological conditions;
there can be no doubt tha-t the leucocytes that subsequently pass

xiv THE LYMPH 533

into the lymph and blood are generated and multiply in these
organs. The most convincing experimental evidence is that
given by Briicke. In carnivorous animals the lymphatic glands
of the mesentery are all collected into a large semilunar mass
known as the "pancreas of Asellius," which lies at the root of
the mesentery. If a little lymph is collected from the lymphatics
of a cat's mesentery, fed on a diet as free from fats as possible, the
fluid is clear and contains hardly any corpuscles. If the lymph
of the efferent lymphatic of the so-called pancreas of Asellius is
examined at the same time, it is seen to be opalescent, and
contains a great number of leucocytes. Further, we have un-
mistakable pathological evidence of the formation of leucocytes
in the lymphatic glands, since hyperplasia of the lymphatic glands
is associated with leucaemia, that is, an extraordinary increase of
the leucocytes in the blood.

The mechanism of the escape of leucocytes from the adenoid
tissues where they are generated and develop, is rather more
complicated in the lymphatic gland than it is in the solitary
follicle. It is certain that the smooth muscle fibres of the
capsule and trabeculae have here an important function, whether
in promoting the lymph stream through the glandular sinuses,
or in driving the leucocytes out of the adenoid rete and propelling
them into the efferent lymphatics. For when these muscular
elements contract (as can be experimentally brought about by
electrical excitation of the ganglion), tire capsule and the trabeculae
exert pressure directly on the circumfollicular sinuses and indirectly
upon the whole parenchyma of the gland, so that all the lymphatics
are emptied like a squeezed-out sponge through the efferent
lymphatics. When, on the contrary, the muscle cells relax, the
lymph sinuses swell up again, and are filled with lymph (Briicke).
In addition to this lymph apoie tic function, we may reasonably
hold that adenoid tissues in general are the seat of an exchange
of materials between the blood and the lymph. We are unable to
gauge the physiological importance of this exchange, which may
be enormous, since it is impossible to examine the phenomena
of absolute deficiency of the lymphatic glands, which are able to
act vicariously and supplement each other. It is further probable
that many of the katabolic products poured out by the tissues
into the lymph stream, which if directly reabsorbed into the
blood would exercise a toxic action, are rendered innocuous and
even beneficial to the organism by the specific activity of the
numerous lymphatic glands through which they pass before
rejoining the blood. To give an ..experimental basis to this
hypothesis, Asher and Barbera studied on the dog the effect on
arterial pressure and pulse frequency, of injecting into the central
end of the carotid either defibrinated lymph from the head or
neck (obtained by continuous centripetal massage of those parts,

VOL. i 2 M a

534 PHYSIOLOGY CHAP

so that it remained as short a time as possible in the lymphatic
glands), or defibrinated arterial, or lastly venous blood from the
same animal. They showed that it was only after injection of the
lymph that decided modifications appeared in the curves 01
arterial pressure arid pulse frequency. The lymph obtained by
continuous massage thus contains specific substances that do not
exist in the arterial and venous blood of the same animal. It
is therefore probable that these are destroyed and modified in the
adenoid tissue of the lymphatic glands (in consequence, as it seems
to us, of the metabolism of the leucocytes accumulated there in
large quantities). Gabritschewski also put forward the suggestion
that the leucocytes absorb certain substances noxious to the body
by transforming them into innocuous substances, a phenomenon to
which he gives the name of pinocytosis.

We must also assign a protective function, in the mechanical
sense, to the lymphatic glands, owing to their labyrinthine
structure, by which they function as filters to arrest, or at any
r.ite retard, the entrance into the blood of many pathogenic
microbes. This is proved by the fact that in miners, and also in
tobacco smokers, the reticulated tissue of the bronchial glands is
impregnated with pigment due to the particles of carbon intro-
duced into the bronchi with the inspired air.

VIII. Among the lymphoid tissues Bone Marrow has acquired
a capital importance, ever since in 1865 Bizzozero in Italy and
Neumann in Germany discovered its haeniapoietic functions. Three
different varieties of marrow can be distinguished : red marrow,
yellow marrow, and gelatinous marrow. The red marrow is found
in the spongy strata of the fiat bones and proximal epiphyses
of the long bones of the extremities (Neumann). Yellow marrow
is found in the adult in the distal epiphyses of the long bones
of the limbs, and is the result of infiltration and fatty degeneration
of the red marrow, which gradually increases with growth and old
age. In consequence of fasting, and in various morbid states with
general emaciation, the yellow is transformed into gelatinous
marrow, but does not lose its capacity for reconversion into yellow,
taking up fresh supplies of fat.

Special interest attaches to the red marrow, which presents a
spongy mass, supported by reticular adenoid tissue (which, as
already stated, consists of fixed and ramified connective-tissue
cells and a rich plexus of branching blood-vessels). The nutrient
arteries that enter the bones divide at once into a number of
branches, which resolve themselves into a capillary network ; this
passes into a system of venous lacunae partly or wholly wanting
in organised walls, in which the blood moves very slowly; out
of this lacunar or cavernous rete arise the small veins by which
the blood flows out. It is notable that the veins that occur
within the medullary tissue are wholly deprived of valves, while

XIV

THE LYMPH

535

those that issue from the bone are furnished with an extraordinary
number of them.

The cells contained in the lacunar system of the marrow are
quite characteristic of this tissue. Among them four principal
kinds can be distinguished : leucocytes, megacaryocyfces (giant
cells), erythroblasts, erythrocytes.

The leucocytes of bone marrow comprise many varieties, which

FIG. 252. — Leucocytes from dog's bone marrow, dry preparation, a, //, Young leucocytesior
lymphocytes, with giant nuclei and little cytoplasm ; c, d, medullary cells or adult leucocytes
with reniform and polymorphous nuclei ; e, leucocytes undergoing mitotic division.

probably represent different states of development of a single
cellular type, since there are always numerous transitional forms
from the one to the other variety. The differences lie in the
dimensions, form of nucleus,
and character of cytoplasm.
The youngest (lymphocytes)
are the smallest, owing par-
ticularly to the paucity of pro-
toplasm around the nucleus ;
the disc -shaped nucleus is
rich in chromatin. The more
adult (medullary cells) are
larger, with a reniform
polymorphous, sometimes
multiple nucleus, poor in
chromatin. These are not
found in normal circulating
blood, only in states of leu-
caemia (Fig. 252).

Howell's megacaryocytes
were discovered in 1869 by
Bizzozero, who called them giant cells with a
nucleus. They have an average diameter of 25-45 //. Their
nucleus is very variable in form, often horseshoe-shaped. Heiden-
hain distinguishes several types or varieties according to the different
degree of differentiation of the cytoplasm, which is sometimes
arranged in three concentric zones (Fig. 253). Bizzozero had
already suggested that the giant cells were derived from the
leucocytes of bone marrow, since there is a whole series of forms

FIG. 2;13. — Megacaryocyte of bone marrow, in which
a large horseshoe nucleus can be distinguished
from the cytoplasm, divided into three concentric
zones. (Heidenhain.)

budding central

536

PHYSIOLOGY

CHAP.

intermediate between the two. The leucocytic origin of the giant
cells is nowadays admitted by every one, although the process by
which the one form of cell passes into the other is still unknown.

The erythrocytes, or nucleated red corpuscles, were described
in 1868 by Bizzozero and Neumann, who recognised that they

Fin. 254. — Erythroblasts and erythrocytes from bone marrow of dog, dry preparation. «, l>, c,
Erythroblasts with more or less developed and excentric nucleus ; d, erythroblasts in mitotic
division ; e, f, erythrocytes apparently destitute of nucleus.

contained haemoglobin. Among them may be distinguished
young forms, adults, and those undergoing mitotic division. They
can easily be differentiated from the lymphocytes of the same size,
not only by the haemoglobin which they contain, but also by the

FIG. 255. — Preparation of human bone marrow, showing the various migratory cells, implanted in
the lacunae of an adenoid tissue, leaving large irregular spaces here and there, which are
occupied by adipose tissue. (B<">hm and v. Davidott'.)

different reaction of their cytoplasm to certain stains. Erythro-
blasts never in their different stages of development present any
cytoplasmic granulation, such as stains with indulin (Trambusti).
In their constitution as in their size, the erythroblasts exactly
resemble the apparently non-nucleated erythrocytes of the blood,
which are found mingled with the nucleated cells of bone marrow.

XIV

THE LYMPH

537

Fig. 255 gives an idea of the mode in which these multiple
elements are connected and intermingled in the areolar tissue of
human bone marrow.

From what has been said, the great functional importance
of bone marrow will readily be admitted. The red marrow, like
all other lymphoid tissues, certainly contributes to lymphapoiesis,
owing to its content of leucocytes at various stages of development.
Since the different varieties of leucocytes differ in chemical
constitution — inasmuch as they show granulations that stain
differently with special pigments — it is not improbable (as sug-
gested by Trambusti) that their specific metabolism may serve for
special functions, of which, however, we are at present entirely
ignorant.

It is more interesting to consider the functions of the mega-

FKJ. 250. — Megaearyocyte of bone marrow, with resting nucleus and linely granular cytoplasm,
differentiated into three layers, and containing five leucocytes in process of digestion.
(Trambusti.)

caryocytes, on which much work has been done. The cytoplasm of
some of these (particularly in the first stages of acute infections
experimentally produced in animals) often contains corpuscles,
which in their characteristics in no way differ from common
leucocytes (Fig. 256). They were at first regarded as leucocytes
in process of formation by endogenous mitosis, or gemmation of
the nucleus of giant cells. Later researches have shown, however,
that they are worn-out leucocytes in process of degeneration,
which are actively absorbed by the giant cells, and are destined to
be digested by them. It is possible under the microscope to
follow the different phases of digestive necrosis of the ingested
leucocytes, by means of double staining with safraniu and indulin
(Trambusti). These observations exclude the suggestion of
Heidenhain, that in cases in which leucocytes are included in
giant cells the former are the active invaders, and the latter the

538 PHYSIOLOGY CHAP.

passive victims doomed to destruction. Other observations,
moreover, show that when the giant cells exhibit signs of necrosis,
they never contain leucocytes, as would be the case if Heidenhain's
interpretation were true. It is evident, therefore, that the
inegacaryocytes fulfil a phagocytic function within the body,,
which probably serves to free the lymphapoietic organs from the
leucocytes that are dead or in process of dissolution (van der
Stricht).

P. Foa (1899) has recently investigated the experimental
conditions under which it is possible to obtain the phenomenon
of phagocytosis upon a large scale with these uiegacaryocytes. He
found it appeared vigorously in inanition, extensive burning of
the skin, and with intravenous injections of lecithin, milk, and
bacterial proteins, especially in gravid or very young rabbits
of VOD-SOO grams, in weight. Under all these conditions the
megacaryocytes were seen to contain numerous polymorphous
leucocytes within their protoplasm, some of which had already
undergone protoplasmic dissolution and nuclear fragmentation, on
the way to their complete disappearance. At the same time, the
protoplasm of the inegacjiryocytes was seen to undergo alteration
and disruption, and their nucleus shrank, and passed free into the
circulatory torrent, where it blocked the capillaries of the lungs
and was finally disintegrated. These two phenomena : destruction
of leucocytes by the megacaryocytes, and embolism of pulmonary
capillaries by the liberated nuclei of the giant cells, are always-
combined, and may be noted in a lesser degree under normal
conditions as well, particularly during pregnancy. In pathological
states the phenomenon is exaggerated, and indicates destruction of
leucocytes that are no longer capable of functioning..

Other notable facts show that the megacaryocytes exert an
important secretory function in regard to the regeneration of the
blood. In fact, after repeated bleeding of the rabbit, their number
conspicuously increases (van der Stricht, Bambeke, Heidenhain).
The external zone of their cytoplasm (which stains less readily)
exhibits bud-like protuberances, which increase in volume, and
become clearer in consequence of the increasing amount of fluid
imbibed by the delicate reticulum (Fig. 2'53). At a later stage
the said buds fuse one into the other, and form large clear vesicles,
in which it is no longer possible to distinguish the protoplasmic
network. When the intracellular tension of the secretory
product has reached its maximum, the fluid pours out, and the
distended protoplasmic reticulum contracts again to form a new
external stratum of cytoplasm. It should be noted that the bone
marrow of rabbits which have been freely bled seldom exhibits
leucocytes ingested by giant cells, showing that under these
conditions the secretory function of the latter predominates.

We are ignorant of the precise physiological destination of the

xiv THE LYMPH 539

products elaborated in the giant cells. But from the very im-
portant fact discovered by van der Stricht to the effect that in a
case of progressive pernicious anaemia there was complete absence
of giant cells in the bone marrow, it may be assumed that they
are useful to the production of erythrocytes.

The simultaneous presence in bone marrow of erythroblasts
(nucleated embryonic red corpuscles) and erythrocytes (adult red
corpuscles with no visible nuclei) shows beyond doubt that it
is the seat of an active formation of the latter which are
found in the blood in large numbers. After repeated bleeding the
haematopoietic function of the bone marrow is conspicuously
increased. The number of haematoblasts undergoing mitotic
division increases ; even that part of the marrow of the long
bones which is normally inactive assumes a haematopoietic function
(Orth, Litten, Foa and Pellacani, Bizzozero and Salvioli). Under
these conditions a large number of nucleated red corpuscles enter
the circulatory torrent (Erb).

Alterations in bone marrow can also be observed in many
diseases in which there is marked alteration of the corpuscles
(leucaemia, pernicious anaemia, typhoid, smallpox).

According to Danilewski and Selenski the subcutaneous or
intraperitoneal injection of watery extracts of bone and splenic
marrow produces a considerable increase in the number of
erythrocytes (up to 50 per cent) and the haemaglobin content
(up to 40 per cent) of the blood of rabbits and dogs. This effect
was confirmed by Fowler in regard to extract of bone marrow.

It was formerly admitted (Bizzozero), and is still retained by
some authors (Paladino), that erythrocytes arise from direct
transformation of leucocytes. This theory, for which there is
no experimental evidence, is now being given up. The only
well-established fact is that the erythrocytes increase by mitotic
division.

On the other hand it is certain that adul-t erythrocytes are
derived from embryonic haematoblasts. The blood of the human
foetus at the fourth month contains only nucleated red corpuscles ;
at the end of the ninth month these have become very rare.
After that they are completely replaced by erythrocytes with no
perceptible nucleus. How does the disappearance of the embryonic
nucleus of the mammalian erythrocyte come about ? Eindneisch
asserts that there is active extrusion of the nucleus ; the haemato-
blast is deformed into the shape of a bell or watch-glass, the
vertex of which, containing the nucleus, is finally disrupted. The
bi-concavity of the erythrocytes is a vestige of this enucleation,
which may be regarded as a kind of autocastration. The majority
of observers hold more simply that the embryonic nucleus
atrophies gradually, and ends by disappearing. If, however, this
view were well founded we ought to find a number of transitional

540 PHYSIOLOGY CHAP.

forms intermediate between the erythroblast and the eventual
erythrocyte, whereas, on the contrary, every one admits that the
transitory forms are rarely met with. The question must, there-
fore, be regarded as unsolved.

Petrone (1898-99) thought he had demonstrated that, while
apparently deprived of nuclei, the erythrocytes, when subjected to
the action of special reagents, contain a body which has all the
cytological and chemical characters of the nucleus. In order to
see this it is only necessary to make an extract of living blood
with a 1 in 4000 solution of osmic acid. In successful preparations
the erythrocytes are seen under the microscope to be in good
preservation, perfectly globular (no longer bi-concave), with a
homogeneous content. At the centre, or more or less at one side,
they exhibit a body with wavy or dentate outline, in which a fine
filamentous-granular structure may be detected. This alone stains

electively with nuclear

/^^.^ ^flhfev s^a^ns' while the rest of the

\ & x\ /^ H erythrocyte stains with

/ r ?; Vs '3y protoplasmatic dyes (Fig.

$s x-_>^ 257). According to Petrone

the supposed nucleus of
the circulating erythro-

/^ /^ . ML cytes is almost always in

I^B^^H a s^e °f complete rest,
\| although he thinks it pre-

mature to say that it is

FIG. 257.- Erythrocytes of healthy man, -showing the entirely lacking in gCI-

more or less central or excentric corpuscles which minative activitv He

Petrone holds to be permanent nuclei. From blood . J '

immersed in 1:4000 osmic acid, subsequently treated thinKS it probable that

with baths of picric acid, and then stained with formic ji *r J~ J~ j.u

haematoxylin and aurantia. thlS depends Upon the

comparatively short life

of the erythrocyte, and the predominance of a special iron-carrying
haemoglobinogenic function which he attributes to it.

The work of Negri (1900), however, invalidates Petrone's
conclusion that the part of the protoplasm which is shown up by
his method of staining can really be interpreted as the nucleus of
the erythrocytes. Negri found that this characteristic body can
always be demonstrated, on using Petrone's method, in the true-
nucleated erythrocytes as well, independent of the nucleus proper,
both in the blood of the mammalian embryos and in the blood of
such adult animals as normally contain nucleated corpuscles (birds
and amphibia).

IX. Among the lymphoid organs we must also include the
Thymus, which consists of a collection of closed follicles, separated
by septa or trabeculae of connective tissue. The section of a lobe
of the thymus shows under a small magnification a cortical and a
medullary substance, which recalls the structure of the lymphatic

xiv THE LYMPH 541

glands (Fig. 258). The reticulated adenoid tissue and a rich
network of blood capillaries support it, with finer meshes in the
cortical part and wider meshes in the medulla. The cellular
elements of the reticulum are collected more abundantly in the
former than in the latter. The arrangement and relations of the
lymphatic vessels in the thymus are still imperfectly determined.
The thymus begins to develop in the earliest periods of
embryonic life. In man the development is rapid between the
third and ninth months. It is, however, a fallacy to hold that the
thymus is exclusively a foetal organ, because it continues, though
slowly, to grow after birth, up to the second year of life ; it
remains stationary till the tenth year, after which it gradually
atrophies and undergoes fatty degeneration. The process of
involution is not unusually much retarded : it is found, for example,

Pio. 258.— Section of lobule of child's thymus. (Buhm and v. Davidott.) The hiluin and critical
substance are seen in distinct follicles, separated by delicate trabeculae, while the medullary
substance is formed by an adenoid tissue with larger meshes.

at the age of twenty-five ; even at an advanced age the thymus
has been found well developed.

From the fact that in reptiles and amphibia which have no
lymphatic glands the thymus is a persistent organ, functioning
during the whole of life, we may conjecture that its functions are
very similar to those of the lymph glands.

That we must ascribe to it a lymph apoietic function is shown
by the fact that the majority of the cells contained in its follicles
are represented by lymphocytes of varying magnitude, some of
which may be seen undergoing mitotic division. Whether it also
has a haemopoietic function is less certain, although some have
distinguished among the thymus cells nucleated red corpuscles,
i.e. erythroblasts proper, such as are observed in bone marrow.

Eecent physiological work on the effect of total or partial
extirpation of the thymus, performed on puppies and chickens at
different stages of development, and particularly on frogs, has

542 PHYSIOLOGY CHAP.

brought to light some very interesting phenomena, which indicate,
however indefinitely and incompletely, the functional importance
of this organ.

Kestelli (1845) was the first who attempted extirpation of the
thymus on lambs, dogs, and calves, without, however, obtaining
any practical results. Friedleben (1858) resumed the experiments
with better success. He succeeded in keeping alive several dogs
on which lie had operated by excising the thymus alone, or the
thymus and spleen together. He did not, however, pay much
attention to the age of the animals on which he was experimenting,
nor did he undertake comparative experiments under perfectly
comparable conditions. In the animals deprived of their thymus
he noted increase of water in the blood (hydraemia), increase of
leucocytes (leucocythaeinia), and diminution of erythrocytes (oligo-
cythaemia) ; conspicuous reduction in the carbonic acid given off
in the time unit ; general trophic disturbances, particularly in the
bony, and also in other tissues. He concluded that the thymus is
not an organ indispensable to life, although it if, highly important
shortly after birth, since during the development of .the body it
promotes nutrition, formation of the blood, and also, therefore, of
the tissues. Nothing was added to these results in a short paper
published by Langerhans and Savaliew (1893).

At the International Medical Congress in Eonie (1894) Tarulli
and Lo Monaco communicated the first results of their experiments
as performed in our laboratory, which were subsequently completed
and published in a larger memoir.

By means of the Thoma-Zeiss method, they confirmed the fact
already stated by Friedleben, to the effect that dogs deprived of
their thymus exhibited a more or less pronounced state of anaemia,
consisting in a diminution of erythrocytes and increase of leuco-
cytes. They added, however, that this was only a temporary
effect, and that two or three months after the operation the
number of blood-corpuscles became almost equal to that of the
normal dogs born in the same litter.

Puppies deprived of their thymus are stunted in growth, weigh
less, and have more flaccid muscles than the control animals. The
difference is especially conspicuous a month or a month and a half
after the operation ; later on it dies out gradually, and cannot be
detected after about three months. The hair differs both in length
and pigmentation in puppies with and without a thymus. Gener-
ally speaking the coat of the latter is rougher, without the normal
gloss and resistance, and yields to the slightest pressure. Sometimes
the bones of the limbs are longer, thinner, and more bowed in
puppies with no thymus ; sometimes there is an exaggerated
development of head at the expense of the rest of the body.

Puppies with no thymus further show reduced resistance and
capacity for muscular work ; they seldom leave their bed, and are

xiv THE LYMPH 543

tired after a lew steps; they can hardly drag a weight much
lighter than that drawn easily by normal puppies. The difference
is very marked even two months after the operation ; it then
diminishes, and finally disappears. In the first two months after
the operation these puppies easily fall ill and die without any
particular cause. Nothing abnormal can be detected at the post-
mortem, except that the gastro-intestinal mucosa is congested.

The effects of extirpating the thymus in chicks 4 to 5 days old
are more apparent. Immediately after the operation they exhibit
only the effects of operative traumatism, which soon passes off, so
that nothing abnormal is seen the next day. Three to four days
after the operation, however, motor disturbances appear, and go on
increasing : weakness of limbs, uncertain gait, slight tremors of all
the muscles, finally torpor, followed shortly after by death. In 18
operated chicks, 15 died with these symptoms 7 to 8 days after
the operation ; 2, in which the disturbances were less pronounced,
recovered after 10 to 12 days: one only succumbed during the
operation.

Of 6 chicks, deprived of the thymus on one side only, one
alone (operated on 2 days after birth) perished, the symptoms
resembling those of chicks in which both sides were operated on :
the others survived, merely exhibiting a slight weakness in the
first days after the operation.

In chicks of 10 to 25 days the excision of the thymus, either on
one side or on both, produced no perceptible effect.

In the interval between the first and second publications of
Tarulli and Lo Monaco, two French experimenters, Abelous and
Billard (1896), published their work on the effect of thymus
extirpation in the frog, which (as might be anticipated) is more
marked than in the case of birds, the thymus in amphibia being a
permanent organ, functioning throughout life.

One to two days after the bilateral excision of the thymus, the
frog exhibits serious motor disturbances, as shown in progressive
muscular debility and incapacity for work, which increases till it
amounts to paresis, paralysis, and the death of the animal. It is
remarkable that while neuro-muscular activity becomes exhausted,
sensibility remains intact, and even increases at first.

Some hours after the operation the copper-green colour of the
frog (Rana esculenta) changes to a yellowish hue, and the area of
black spots is contracted ; only the head and limbs escape this
discoloration. On the following day this phenomenon is less
pronounced ; with the onset of the muscular weakness it reappears,
and increases steadily till death. Along with the discoloration
dystrophic effects begin to appear On the skin in the form of
ulcers, zones of necrotic destruction, and subaponeurotic ecchymoses.
These changes become more serious the longer the animal survives.
The ulcerated surfaces are highly hyperaemic, and bleed at the

544 PHYSIOLOGY CHAI>.

least touch. These animals may be said to have become
haemophilia.

Most frogs at the moment of death exhibit dropsy. Directly
the abdomen is opened or the muscles cut through, a colourless or
bloody transudate escapes.

The blood from the heart is more watery ; the erythrocytes are
changed in form and colour, and are fewer in number, while the
leucocytes are increased. The peritoneum, bladder, stomach,
intestine, other abdominal viscera, and the cervical region of the
cord are all more or less congested.

Undoubtedly death results from functional defect of both lobes
of the thymus. It invariably occurs, but after an interval which
varies from 3 to 4 days. It ensues equally when the two organs
are excised at different times, with a longer or shorter interval
between the two operations. After the extirpation of one thymus
only nothing abnormal appears save a lessened resistance to
fatigue. If the second thymus is exposed 15 to 20 days after, it
exhibits a certain degree of hypertrophy. Its excision is rapidly
followed by the disturbances aloove described, and death ensues in
a short time.

If the blood or serum from the peritoneal cavity of a frog that
is dying from ablation of its thymus glands is injected into a
frog that is normal or deprived of one or both thymuses, more or
less pronounced disturbances of function will be observed in all,
which may produce death even in normal frogs, induce it almost
inevitably in frogs with only one thymus, and greatly accelerate
it in frogs deprived of both organs. This fact shows that the
tissue fluids of the frog entirely deprived of thymus contain
energetically toxic substances, and that the fundamental function
of the organ consists in the destruction of these, or in rendering
them innocuous.

Transplantation or grafting of the excised thymus beneath the
skin of the same frog or of another deprived of its thymus, does
not inhibit the phenomena of auto-intoxication above described.
Abelous and Billard, however, observed a temporary abatement of
the phenomena of discoloration. On the other hand, subcutaneous
injection of extract of calves' thymus (calves' thymus 20 grms., solu-
tion of boric acid 100 grrus.) in 1 c.c. doses containing 0'02 grm. of
thymus, both in normal frogs and in those which have been partly
or wholly deprived of the thymus, produce effects resembling
strychnine convulsions, while at the same time cutaneous dis-
coloration ceases, and the normal colour of the skin becomes
more pronounced. Accordingly there is a true antagonism
between the phenomena of thymus deficiency and those produced
by injection of the extract of this organ.

Ver Eecke (1899) also worked on the frog's thymus, coming to
conclusions which differed in some respects from those of Abelous

xiv THE LYMPH 545

and Billard. According to ver Eecke the function of the frog's
thymus is subject to periodical oscillations similar to those of
bone marrow. He found that the frog's thymus undergoes
functional atrophy in winter, and an analogous state can also be
observed in summer if the frog is made to fast. The functions of
the thymus are thus closely associated with those of the digestive
organs. Possibly it further has an antitoxic action. Both during
the winter season and in summer, if the animal is made to fast,,
the thymus is not indispensable to life. Its partial or total
excision, whether uni- or bi-lateral, under these conditions has no
effect other than to weaken the resistance of the animal to external
intoxications.

Basch (1903), after thymus extirpation, noticed alterations in
the ossification of the long bones. In animals without a thyinus
the formation of callosities and union of the fractured bones
occurred later than in the normal. The animals operated on
eliminated a larger amount of calcium than the control animal,
amounting sometimes to five times the quantity.

Svehla (1896-1900), on injecting a watery extract of the
thymus of man and other animals (pig, ox, dog) into the circula-
tion, noted in dogs that there was acceleration of pulse and
diminution of blood pressure, an effect resembling that of the
injection of thyroid and suprarenal extracts. According to the
latest experiments, it appears more probable that this action of
thymus extract is due not to a specific substance in the thymus —
as is the case with the suprarenal capsule — but to the various
substances, nucleoproteins in particular, which are dissolved in the
water, and are found generally, without exception, in every organ.
A similar action has in fact been observed after the injection of
extracts of many other organs (Hammarsten).

Cervesato attempted organotherapy with the thymus, starting
from the fundamental concept that this organ in man functioned
during infancy, and that this may be the reason why infants are
less readily attacked by or are even immune from certain diseases.
Stoppato describes the results obtained by the administration as a
food of raw or undercooked thymus in doses of 29-40 grms. a day,
in four cases of infantine atrophy, and in one case of infantine
anaemia. In all these he obtained very encouraging results after
a two -months' regime ; there was marked improvement in the
general state of nutrition, with development of body weight and
increase of erythrocytes and haemoglobin of the blood. On the
other hand, the results obtained from children afflicted with rickets
and abdominal scrofula were insignificant, which points to the
specific character of the therapeutic action, and therefore to the
normal function of the thymus as an organ affecting general
metabolism.

X. The Spleen is the largest lymphoid organ, its structure
VOL. i 2 N

546 PHYSIOLOGY . CHAP.

corresponding to that of the lymphatic glands, thymus, and red
bone marrow — which justifies us in assuming that the function of
all these organs (apart from their specific differences) is closely
allied, so that they are to some extent able to supplement each
other, or to act vicariously. Besides its peritoneal sheath the
spleen has a capsule, consisting of fibrous elastic and muscular
tissue. A number of trabeculae dip into the organ from the inner
surface of the capsule, dividing and subdividing, so that the
parenchyma is converted into an elastic and contractile network,
with large and small meshes, the hollow spaces of which contain
the so-called splenic pulp (Fig. 250).

Fi<;. ^59.— Vertical section through a fragment of human spleen, low magnification. (Kolliker.)
A, Peritoneal and librous capsule ; b, b, trabeculae ; c, c, Malpighian corpuscles, one of
which shows the transverse section, and the other the long section, of an artery ; d, injected
arterioles ; e, splenic pulp.

When the spleen is cut across and squeezed, the pulp escapes,
looking like blackish coagulated blood, which after exposure to the
air assumes a lighter reddish hue. On examining a thin section
of spleen treated with dilute solution of potash under the micro-
scope, the splenic pulp is seen to be contained within the unequal
meshes of a lymphoid tissue that supports it, and is composed of
fringed connective cells, which ramify and anastomose among
themselves, and are in connection with the trabecular tissue
(Fig. 260).

The splenic vein and artery are remarkable for their size
relative to the volume of the body which they irrigate. After
penetrating the hilum to the interior of the spleen by six or more
branches, they ramify dendritically, still within the trabeculae,

XIV

THE LYMPH

547

which cover them with an adventitious lyniphoid sheath. In the
small arteries this sheath dilates here and there into grey nodules,
oval or spherical, of various sizes (1-0'36 mm. in diameter), similar
in structure to the solitary follicles of the intestine, and known as

FIG. '260. — Thin section of splenic pulp neai1 the origin of a small vein, highly magnified. (E. A.
Schafer.) v, Venule filled with red and white blood-corpuscles ; bl, erythrocytes which till
the interstices of the reticular tissue of the pulp ; p, branching connective-tissue cells which
form the reticulum containing the pulp.

Malpighian nodules or corpuscles, after their discoverer. These
nodules, for the most part, develop laterally to the small arteries,
from which they receive twigs that irrigate the follicular tissue
(Fig. 261). Under
the high power, each
Malpighian corpuscle
shows a complex reti-
cular structure, by
which they are differ-
entiated from the
hoinonymous tissue of
the splenic pulp (as
shown in Fig. 262,
which represents a
preparation obtained
by the silver chromate
method).

The small arterial

ranii, after leaving the FIO. -201.— Small splenic artery (dog), with many Malpighian
r i , -i corpuscles attached to the peri vascular lymphatic sheath ;

trabecular tissue and m^flcationofiodtebetew: (iwiiiker.)
penetrating the areolar

labyrinthine tissue which contains the pulp, divide into small
feathered tufts of arterioles;- they afterwards lose their tubular
form and continue, in the opinion of most histologists, not in
the usual way by a closed capillary network into the veins,

548

PHYSIOLOGY

CHAP.

but by opening freely into the labyrinthine spaces of the splenic
reticulum. From the same reticulum the roots of the small veins
(see Fig. 260) arise by an opposite process and then open into
those which course along the trabeculae.

The lymphatics of the spleen form plexuses in the capsule and
in the trabeculae. They are not very numerous, and run with
the arteries, sometimes surrounding them, to form a plexus. The
perivascular adenoid tissue and the follicles composed of the
Malpighian nodules communicate with the lymphatic vessels with

FIG. 26^. — Section of Malpighian corpuscle and surrounding tissue of splenic pulp, with injected
network of blood capillaries, treated with silver chromate ; highly magnified. (Oppel.) 1,
.Malpighian corpuscle ; -2, part of its reticulum ; 3, denser reticulum at the edge of the
corpuscle ; 4, looser tissue external to the former ; 5, (», connective tissue of arterial sheath,
to which the corpuscle is adhering ; 7, capillaries of corpuscle ; 8, reticulum of pulp surround-
ing the arteriole.

proper walls that run in the tissue of the trabeculae. All the
lymphatics issue from the hilum together with the blood-vessels,
and then join the lymphatic ganglia of the posterior part of the
'abdomen.

rf'tfcr The nerves of the spleen are derived from the solar plexus ;
f hey enter by the hilum along with the vessels. They are certainly
in peripheral relation both wjth the muscle cells of the vessels and
with those of the capsule ancl trabeculae. Their central origin is
probably in the bull) and cervical tract of the spinal cord. In
order to reach the periphery, the splenic nerves pass by the left

XIV

THE LYMPH

549

splanchnic and semilunar ganglion, from which arises the splenic
plexus.

According to the histological researches of Retzius, v. Kolliker,
and Fusari, the nerves of the spleen are usually non-niedullated
and for the most part supply the vascular muscles.

From the above it is evident that the blood which penetrates
the spleen by the splenic artery comes into immediate relation with
the elements of the splenic pulp contained in the labyrinthine
spaces, and that the blood which issues from the spleen by the
splenic vein must have traversed the lacunar system.

On examining the mobile elements of the splenic pulp undei
the microscope, they are seen to consist for the most part of
erythrocytes and leucocytes, i.e. of the corpuscles of normal blood,
which, owing to the marked circulatory delay within the lacunar
system, become concentrated with very little plasma.

Besides the ordinary red and white blood-corpuscles, however,

FKJ. '2<>3. — Splenic cells of various forms and sizes, containing in tlieir cytoplasm pigment
granules, and erythrocytes in process of dissolution, or fragments of already dissolved
erythrocytes : magnification of 1'JCO diameters. (From a dry preparation of F. Miiller.)

the splenic pulp contains other elements, similar to those of bone
marrow. Megacaryocytes are rare, at least in man ; on the other
hand, there is an abundance of smaller amoeboid cells (although
still twice the size of common leucocytes), many of which exhibit
erythrocytes in process of breaking up (globuliferous splenic cells)
inside them. There are many intermediate forms between the
ordinary leucocytes and the globuliferous cells, all containing in
their protoplasm extraneous corpuscles of varying form and
magnitude, which represent pigment granules or the detritus of
erythrocytes ingested by phagocytes (Kolliker and Ecker; Fig.
263). The plasma, again, in which these amoeboid cells are
suspended, contains, in addition to the normal erythrocytes^'a
certain number of red corpuscles which are at different stages* oT
disruption, and pigment granules Derived from the decomposition
of haemoglobin.

In the spleen of very young animals, there are constantly
present along with the erythrocytes a greater or less number of
erythroblasts or nucleated red corpuscles in various stages of

550 PHYSIOLOGY CHAV.

development (Funke and Kolliker)- In adult animals, too, after
repeated bleedings, Bizzozero and Salvioli noted the appearance
of haematoblasts, which are absent under ordinary conditions
(Neumann).

In view of these facts, and of what has been stated in regard to
the functions of bone marrow, we cannot doubt that the spleen is a
haemopoietic and haemolytic organ. Its haemopoietic function,
as demonstrated by the presence of the erythroblasts, seems to be
very active during intra- uterine life, when the oone marrow
contains the fewest number of nucleated red corpuscles ; it is
greatly reduced in the first period of extra-uterine life, when the
haemopoietic function of bone marrow increases ; it is abolished in
adults, in whom bone marrow functions in full activity ; lastly, it
recurs in adults under circumstances in which the body requires a
hurried neo-forrnation of the cytological elements of the blood.

That the spleen is not an effective haemopoietic organ in adult
animals has been conclusively demonstrated by the recent work of
Faton, Gulland, and 'Fowler (1902) on dogs, cats, and rabbits.

These authors employed four different methods of research : (a)
comparison of the number of blood-corpuscles present in the splenic
artery or carotid with the number of corpuscles present in the
splenic vein ; (&) determination of the effects on the blood-
corpuscles of extirpation of the spleen ; (c) measurement of the
time it takes in normal and a-splenic animals to regain the normal
mass of corpuscles either after haemorrhage or after the action of
haemolytic agents; (d) study of the action on haematopoiesis
of injections of splenic extract. The following results were
obtained :—

In dogs and cats no difference was observed either in the
number or character of the erythrocytes in the blood that goes to
the spleen, as compared with the blood that flows out from the
spleen. It appears, however, that there is a slight reduction in the
number of the leucocytes, more particularly in that of the poly-
nucleated.

Extirpation of the spleen in dogs, cats, and rabbits has no
, apparent effect on the number of erythrocytes, nor upon the protein
components of the blood plasma (at least in dogs). There appears,
however, to be a slight reduction of the eosinophile leucocytes.
After haemorrhage in rabbits, and haemolysis in dogs, the normal
number of erythrocytes is restored in the same time, both in the
control animals and in those which have lost their spleen. Injection
of splenic extract does not produce any augmentation in the
number of erythrocytes in the rabbit, but they do increase, on the
contrary, after injection of extract of red bone marrow.

From the above data the authors conclude that they have not
established any fact to prove that the spleen possesses a haemo-
poietic function.

xiv THE LYMPH 551

The haemolytic function of the spleen may be argued from
the numerous phagocytes in various stages of development, the
erythrocytes in process of destruction, and the pigment granules
contained in the plasma of the splenic pulp. Analysis of the
chemical constituents of the spleen, moreover, make it probable
that this organ is the seat of highly complex metabolic processes
involving the destruction of many corpuscles.

According, however, to the latest work on dogs, cats, and
rabbits by Paton and Goodall (1903), it appears that the spleen has
no genuine and proper haemolytic function ; but that its work is
confined to the taking up of erythrocytes that are already dead,
and the chemical transformation of their pigment, by storing up
the iron, which can then be utilised for the formation of other
erythrocytes.

On the other hand, W. Bain (1903), by artificially circulating
the isolated spleen and liver of dog, with the object 'of determining
the importance of these two organs in haemolytic processes, came
to the conclusion that both spleen and liver, under these con-
ditions of survival, exhibit the property of destroying erythrocytes
as well as leucocytes. The spleen acts principally upon the
leucocytes, among which it more particularly attacks those with
polymorphous nuclei, although a certain quantity of erythrocytes
(2'4 per cent) are also destroyed.

Besides the chemical compounds present in these highly
vascular organs, there are other special products in the splenic
pulp. One of the most important is a ferric albuminate which
certainly depends on the chemical changes of the haemoglobin in
the erythrocytes broken up by the spleen. The large amount of
iron that can be recovered from the spleen has led some observers
to consider that it is a storehouse of iron destined to the formation
of new haemoglobin.

A series of recent researches by Tedeschi (1899) confirms the
fact already admitted by Kriiger and Lapicque to the effect that
the spleen is an organ rich in iron ; that on an average there is
less in young than in adult rabbits ; and that it seems to
diminish again in old age. This excess of iron in the spleen is
probably derived from decomposition of the haemoglobin of the
erythrocytes broken up in the spleen. This does not, however,
forbid the assumption that part at least of these organic iron
compounds may serve the erythrocytes that pass through the
spleen as materials for the construction of new haemoglobin.
Arguments, in fact, are not wanting to show that the haemoglobin
contained in the erythrocytes of the venous blood that leaves the
spleen is in excess of that contained in the erythrocytes of the
arterial blood that enters it ; consequently the spleen must
take an active part in the formation of haemoglobin and the
maturation of the red corpuscles of the blood. This is indicated

552 PHYSIOLOGY CHAP.

particularly from the work of Gurwitsch (1893) and Zelensky
(1891). The former made 10 minute comparative analyses of the
blood of the carotid and splenic vein in dogs ; the latter determined
on dogs and rabbits the effect of the peritoneal injection of splenic
extract. On counting the corpuscles and estimating the haemo-
globin with Hiifner's spectro-photoineter, before and after injection,
there was invariably a marked rise in both, whence the author
concluded that " splenic infusion contains the products necessary
to the regeneration of the blood."

The lymphoid tissue of the spleen, which consists essentially of
Malpighian corpuscles or nodules, is a lymphapoietic or leucocyte-
forming organ analogous to the lymph follicles and glands
(Virchow). This is plain from the fact that the blood of the
splenic vein contains many more leucocytes than the blood of the
splenic artery (Kolliker and Hirt, Bizzozero and Salvioli). In the
blood of the splenic vein the ratio between the number of the
leucocytes and that of the erythrocytes is as 1 : 60 ; in the
arterial blood, as 1 : 2260. In splenic leucaemia the lympha-
poietic function of the spleen is enormously increased, so that it
sends out a great quantity of leucocytes into the blood torrent.
This fact coincides with a corresponding enlargement of the organ,
due to hyperplasia of the lymphoid tissue.

It is to the wealth of leucocytes in the spleen and their
special metabolism that we must refer the fact that the chemical
compounds of the splenic pulp abound in nuclein and its deriva-
tives, i.e. adenine, xanthine, hypoxanthine, guanine, and uric acid.
Lecithin, jecorin, cholesterin, and inosite are also present. The
alkaline reaction of the splenic pulp becomes acid after a short
time, owing to the development of fatty acids, among which are
succinic, formic, acetic, and lactic acid. The constant presence of
uric acid in the fresh spleen should be noted, even in these
herbivorous animals whose urine does not contain it. Horbaczewski
(1889) states that when a fragment of still living spleen is dipped
into blood freshly extracted from an animal, it induces the forma
tion of considerable quantities of uric acid. This proves the spleen
to be an important, if not the sole, organ in the formation of uric
acid, which, as we shall see elsewhere, is derived from the nuclein
bases present in large quantities in the splenic pulp.

Since the spleen is a contractile organ, its volume undergoes
great variations. Normally it swells during the digestive period,
reaching its maximum five hours after meals ; it remains turgid
for some time, and eventually regains its normal volume. This is
the effect of an active hyperaemia analogous to that which is
simultaneously exhibited by the mucosa of the alimentary cord, the
pancreas, and the other glands attached to the digestive apparatus.
This coincidence in hyperaemia points to the probability of the
active intervention of the spleen in the chemical phenomena of

xiv THE LYMPH 553

the digestive secretion. It seems probable, in fact, from the
theoretical standpoint that the congested spleen, by means of the
nutritive substances freshly absorbed from the digestive apparatus,
produces and pours into the blood substances that favour in some
way the formation of the enzymes which are the active principles
of the gastric (Baccelli) or of the pancreatic juice (Schiff, Herzeii).
We shall return to this point iu another connection. It also
appears highly probable that the spleen and perhaps the lymphoid
organs and tissues in general serve as magazines or reserve stores
for the proteins deriving from digestion, and which cannot be
immediately utilised by the tissues, just as the liver stores up the
carbohydrates that accumulated there, in the form of glycogen. In
favour of this hypothesis we have the fact of the marked reduction
which the spleen and lymph glands undergo during inanition
(Fredericq).

Another important phenomenon observed in clinical practice is
the temporary swelling exhibited by the spleen in many of the
infective diseases that are accompanied by fever. In malarial
fevers the enlargement of the spleen increases constantly, with
repeated attacks, until it becomes permanent and may reach
considerable proportions, either by the accumulation of the
malarial parasites and their products, or, as is probable, by
paralysis of all the muscular elements of the organ. We have
seen that the lymphatic glands swell by a similar process under
similar morbid conditions, and that this process is of great import-
ance in arresting the infective germs, and rendering the toxic
substances which they produce innocuous. The spleen may also
be regarded as an organ of defence against infective agents, which
harmonises perfectly with the fact of the presence of numerous
phagocytes contained in the splenic pulp.

The contractility of the spleen has been tested by direct stimula-
tion of the organ, and by excitation of the peripheral nerves that
run to it, as also by direct or reflex stimulation of the nerve centres.

If the spleen of an anaesthetised dog is exposed, the contact
of the air at first produces a contraction of the organ, which
disappears after some time, its surface becoming supple again, and
dark red. On then bringing together the electrodes from an
induction coil and applying them to any point on the organ, a
hollow and blanching will be produced in consequence of local
contraction, which drives out the blood. On running the
electrodes over the surface of the organ, grooves and white lines of
any form desired can be traced (Briicke). The human spleen has
less contractility than that of the dog, cat, and many other
animals, owing to the smaller number of muscle cells contained in
the capsule and the trabeculae; contraction can, however, be
determined by the percussion method, after faradisation of the
organ through the skin (Botkin).

554 PHYSIOLOGY CHAP.

Koy was able by the plethysinographic method, ingeniously
modified and applied to the spleen in situ, to study the automatic
variations in volume of this organ. He snowed that the spleen 6f
dogs and cats presents periodic contractions and expansions
lasting in all for about a minute, independent of the slow
oscillations of arterial pressure, and therefore of the dilatations
and constrictions of the arteries, which must accordingly be
referred to the periodic contractions and expansions of the muscle
cells of the capsule and trabeculae. The spleen of these animals
is therefore a muscular organ which rhythmically expands to
receive an increased amount of blood, and rhythmically contracts
to expel a considerable part of the blood which it contains, in the
direction of the liver. During its expansion the blood which has
been driven out into the reticuluni of the splenic pulp, and is at
rest there, probably undergoes important metabolic changes;
during contraction the blood whicli has suffered these changes,
and many of the mobile elements that lodge in the areoli
containing the pulp, and the follicular tissue of the Malpighian
corpuscles, are driven out through the efferent vessels of the
organ.

The muscular activity of the spleen, whether of the muscles of
the capsule and trabeculae or of the vessels, is regulated and
controlled by the nervous system. A pronounced and more or
less rapid contraction of the spleen can be obtained by the
electrical excitation of the spinal bulb, the upper cervical cord,
left splanchnic, semilunar ganglion, and lastly the nerve plexus to
the spleen (Tarchanoff). The same effect can be obtained reflexly
by the electrical excitation of a sensory nerve or of the central
end of the vagus. The contraction of this organ during asphyxia
(as also in strychnine or strong quinine poisoning) is also due
to excitation of the nervous system, which governs the muscles of
the spleen. Section of the splenic nerves or their paralysis from
any cause induces the opposite effects, i.e. the passive enlargement
of the organ.

According to Bulgak (1877), the reflex and motor centres for
the muscles of the spleen lie in the cord between the first and
fourth cervical vertebra, while lower down, as far as the eleventh
dorsal vertebra, there are only the afferent and efferent nerve
fibres to the spleen. Schafer and Moore substantially confirmed
these results.

In view of the marked difference in volume which the spleen
exhibits owing merely to fluctuation in the amount of blood that
collects in it, certain physiologists, including Briicke, have looked
upon it as a diverticulum capable of modifying or influencing the
circulation of the other abdominal organs, notably the stomach
and the liver, in various ways. This idea is founded on the
anatomical fact that the splenic artery and the gastric and

xiv THE LYMPH 555

hepatic coronaries are three branches of one trunk, the coeliac
artery, and that in proportion, as the inflow of blood through the
splenic artery is easy or difficult, the blood supply to the stomach
and liver must diminish or increase. Drosdotf and Botschet-
schkaroff saw by direct observation that the contraction of the
spleen induces increased blood supply to the liver. On stimulating
the previously divided nerves of the splenic plexus, and thus
producing a marked contraction of the spleen, the amount of
blood that flows from a puncture previously made on the surface
of the liver is conspicuously increased.

Little has been added to these positive data in regard to
the various physiological functions of the spleen, from the results
of the recent methodical researches on the consequences of its
extirpation. Galen and Pliny were already aware that the spleen
can be excised without danger to the animal. The first splenectomy
performed on man was by Zaccarelli, in 1549. Morgagni mentions
a woman whose spleen was removed in consequence of its protrusion
from an abdominal wound, and who survived the operation for
five years, and subsequently became a mother.

Innumerable experiments have been made in this direction,
and there is probably no physiologist who has not successfully
attempted the extirpation of the spleen at various times, either on
dogs or rabbits. After the introduction of antiseptics, many
surgeons performed the operation on man with a therapeutic
object. Its want of success in cases of leucaemia, of amyloid
degeneration, and of circulatory stasis in the organ is no evidence
that the spleen is essential to human life, while the many
successful operations (66 per cent, according to Vulpius) in cases
of wandering spleen, simple hypertrophy, suppuration, cysts,
sarcomata, etc., show, on the contrary, that it is possible to sur-
vive splenectomy with no ill consequences, provided other serious
lesions are not present.

Not merely can animals resist splenectomy, but it has been
demonstrated by the experiments of Tizzoni (1884) on rabbits,
of Kurlow (1862) on guinea-pigs, of Dastre (1893) on young-
puppies, kittens, guinea-pigs, and mice that this operation neither
perceptibly retards development, nor does it impair the repro-
ductive capacity.

On counting the blood-corpuscles before and after splenectomy
in dogs (Emelianow, 1893), rabbits, and goats (Vulpius, 1894),
a relative diminution of erythrocytes and increase of leucocytes
has been observed. The same fact has often been noted in regard
to man, when splenectomy has been performed, especially in the
cases referred to by Crede, Kocher, Severanu, and Czerny. This
is the only fact that could be invoked in support of the theory
that many leucocytes are transformed into erythrocytes in the
spleen, by taking up or forming haemoglobin, with expulsion of

556 PHYSIOLOGY . CHAP.

the nucleus or its atrophy and reabsorption. We have 'seen,
however, that this theory was contradicted by microscopical
observations of the mobile elements of the splenic pulp, among
which there are normally no erythroblasts nor other transitional
forms between leucocytes and erythrocytes. On the other hand,
the observations of Vulpius show that after at most nine weeks
after splenectomy it is impossible to recognise any difference
between the blood-corpuscles of normal and those of a-splenic
animals, showing that the lymphapoietic-or haemapoietic function
of this organ is readily replaced by either the lymphatic glands
or the bone marrow. It is apparently in this sense that we should
interpret the more recent negative results obtained by Paton and
Gulland, and Fowler, as above cited.

Hypertrophy of the lymphatic glands after splenectomy has
been repeatedly observed on animals as well as man ; but the
effect is not constant, nor is it of long duration, which leads one to
suppose that it is the result of the operative procedure. Even
without any striking hypertrophy, however, it may be assumed
that the lymphatic glands, which are exceedingly numerous, are
capable of vicariously assuming the lapsed functions of the spleen.

Bone marrow sometimes seems to contain a large number of
haematoblasts after splenectomy (Litten and Orth, Emelianow);
in a-splenic rabbits and guinea-pigs it contains more iron than in
intact animals of the same age (Tedeschi, 1899). This functional
substitution is not, however, always apparent, nor in any case is it
indispensable, since in fishes which have no bone splenectomy is
supported without any perceptible alteration of the blood-corpuscles
(Pouchet,- 1878).

Certain observations exist which tend to show that the functions
of the spleen can be partly taken on by the liver. Maggiorani
(1862) stated that the weight of the rabbit's liver in splenectoniised
rabbits exceeded that of intact rabbits by about f ; Montenovesi
(1893) describes a clinical case of hypertrophy of the liver con-
sequent on splenectomy ; lastly, Tedeschi (1899) has recently
shown that the liver of the a-splenic rabbit contains a larger
average amount of iron than the liver of intact rabbits, young or
old. Still these facts do not seem to us sufficiently conclusive to
admit of our assuming that the liver undergoes such modifications
as would enable it to resume the haemopoietic functions which it
performs during the embryonic life. The increase in volume and
weigHt of the liver after splenectomy, as also the increased wealth
of iron, may depend on a more copious blood supply; also, as rightly
suggested by Maffucci, on the fact that this organ, after splenectomy
for malarial hypertrophy, becomes the principal repository for
parasites and malarial pigments.

It has been maintained that the spleen, after total extirpation,
is reproduced or regenerated in the form of one or more lesser

xiv THE LYMPH 557

spleens that did not exist previous to the operation (Vella,
Tizzoni). But it was subsequently discovered that there are not
seldom nodules of a substance analogous to that of the spleen in
its immediate neighbourhood, in the gastro-splenic omen turn and
great omentum, which represent true accessory or supernumerary
spleens, and these after the operation may become more developed
(Foa). It has also been demonstrated that if in the act of excising
the spleen some of the splenic pulp is scattered in the omentum,
it is capable of lodging there and giving rise to the formation of
lesser spleens that did not previously exist (Cecchini and Grimni).
In no case could the capacity of lymphoid splenic tissue to lodge
and reproduce itself be invoked in favour of the theory that
the spleen is an organ indispensable to life. Whatever the
importance of its functions, they may easily be replaced by the
other lymphoid tissues which abound in the body.

Lastly, we must remark that of late years special modifications
of the lymphatic glands have been described under the name of
haemolymphatic glands (Leydig, Gibbes, Kobertsou, Drummond,
Vincent and Harrison, Weidenreich). They are found along the
whole length of the aorta, and are differentiated from the ordinary
lymph glands by the fact that no lymphatic vessels can be
demonstrated in them. Both sinus and the vessels are filled with
blood instead of lymph. According to their histological structure,
they must represent a connecting link between the ordinary
lymphatic glands and the spleen (Vincent and Harrison). In all
probability their function is analogous to that of the other
haeinopoietic organs (Seemann, 1904).

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558 PHYSIOLOGY

CHAP.

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xiii., 1899.

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P. EMELIANOW. Arch, de sc. biol. de St-Pt'tersbourg, ii., 1893.
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Lymphapoiesis : synthetic re.view : —

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Haemapoietic organs :—
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SWALE VINCENT. The Question as to Alteration in the Lymphatic and Haemal

Glands after Removal of the Spleen. Proc. Physiol. Soc. in Journ. of Physiol.,
1899-1900, xxv. pp ii., iv.
L. B. MENDEL and H. C. JACKSON. On Uric Acid Formation after Splenectomy.

Amer. Journ. of Physiol., 1900, iv. 16-3-69.
A MOORE. The Effect of Ions on the Contractions of the Lymph Hearts of the

Frog. Amer. Journ. of Physiol., 1901, v. 87-94.
A. MOORE. Are Contractions of the Lymph Hearts of the Frog dependent upon

Centres situated in the Spinal Cord ? Amer. Journ. of Physio!., 1910, v. 196-8.
F. A. BAINBRIDGE. Observations on the Lymph Flow from the Submaxillary

Gland of the Dog. Journ. of Physiol., 1900-1901, xxvi. 79-91.
L. B. MENDEL and D. R. HOOKEU. On the Lymphagogic Action of the Strawberry

and on Post-mortem Lymph Flow. Amer. Journ. of Physio!., 1902, vii. •

380-86.
Win. STIRLING. Simple Method of demonstrating the Membrane of the Sublingual

Lymph-Sac of the Frog. Proc. Physiol. Soc. in Journ. of Physiol., 1901-2,

xx vii. p. i.
R. MAGNUS and E. A. SCHAFER. Does the Vagus contain Motor Fibres for the

Spleen? Proc. Physiol. Soc. in Journ. of Physiol., 1901-2, xxvii. p. iii.
D. N. PATON, G. L. GULLAND, and J. S. FOWLER. The Relationship of the Spleen

to the Formation of the Blood Corpuscles. Journ. of Physiol., 1902, xxviii.

83-106.
F. A. BAINB RIDGE. On the Formation of Lymph by the Liver. Journ. of Physiol.,

1902, xxviii. 204-219.
W. BAIN. The Role of the Liver and Spleen in the Destruction of the Blood

Corpuscles. Journ. of Physiol., 1903, xxix. 352-68.
D. N. PATON and A. GOOD ALL. Contribution to the Physiology of the Thymus.

Journ. of Physiol., 1904, xxxi. 49-64.
J. HENDERSON. On the Relationship of the Thymus to the Sexual Organs — I.

Journ. of Physiol., 1904, xxxi. 222-33.
F. A. BAINBRIDGE. The Lymph Flow from the Pancreas. Journ. of Physiol.,

1905, xxxii. 1-7.
D. N. PATON. The Relationship of the Thymus to the Sexual Organs — II. Journ.

of Physiol., 1905, xxxii. 28-32.
F. A. BAINBRIDGE. The Post-mortem Flow of Lymph. Journ. of Physiol., 1906,

xxxiv. 275-81.
A. J. CARLSON, J. R. GREER, and F. C. BECHT. On the Mechanism by which

Water is eliminated from the Blood in the Active Salivary Glands. Amer.

Journ. of Physiol., 1907, xix. 360-87.

xiv THE LYMPH 559

W. T. HUGHES and A. J. CARLSON. Relative Haemolytic Power of Serum and
Lymph under Varying Conditions of Lymph Formation. Amer. Journ. of
Physiol., 1908, xxi. 236-47.

A. J. CARLSON, J. R. GREEK, and A. B. LUCKHARDT. Contributions to the

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A. B. LUCKHARUT. Contributions to the Physiology of Lymph. Amer. Journ. of
Physiol., 1909-10, xxv. 345-53.

H. O. LTJSSKY. Contributions to the Physiology of Lymph. Amer. Journ. of
.Physiol., 1909-10, xxv. 354-66.

INDEX OF SUBJECTS

Abdominal respiration, 416
Absorption of gases, 378
Acapnia, 474
Accelerators, heart, 327
Accessorius, nerve, 328
Acid, aereal, 373

amino-iso-valerianic, 27

aspartic, 27, 129

butyric, 37

caproic, 35

carbonic, blood, 380, 385, 397

carbonic, discovery, 373

carbonic, expired air, 389, 395

diamino-trioxy-dodecanic, 27

glutamic, 27

hippuric, 129

lactic, plasma, 130

lactic, urine, 470

laevulinic, 24

nucleic, 24, 138

oleic, 35

oxalic, 60

oxypyrrolidine-carboxylic, 27

palmitic, 35

a-pyrrolidine-carboxylic, 27

stearic, 35

uric, 129, 552

valerianic, 35
Acid albumin, 23
Actinosphaerium Eichhornii, 74
Adaptation, 49, 63, 65

of respiration, 469
Adenase, 33
Adenine, 24, 33, 35
Adynamia cordis, 333
Aerobic organisms, 68
Aerotonometer, 388, 490
Afferent nerves, heart, 333

nerves, respiration, 457, 464
Agminated follicles, 530
Air, alveolar, 390

complemental, 423

expired, 397

inspired, 397

reserve, 423

residual, 423

tidal, 423

VOL. I

1 Ala cinerea, 445
Alanine, 23, 27
Alanyl-glycine, 23
Alanyl-leucine, 23
Albuminate, ferric, spleen, 551
Albuminoids, 23
Albumoids, 25
Albumose, 23
Alcoholase, 34
Aleuron, 18
Alexines, 154
Alkali albumin, 23
Alkalimetry, blood, 96
"All or nothing," 318
Allonomous metabolism, 87
Allorhythmia cordis, 316
Alveolar air, 390

pressure, 405
Alveoli, pulmonary, 403
Amoeba, 14
Amoeboid movement, 74

movement, leucocytes, 115
Amino-acids, 27, 129
Ammonia, plasma, 129
Amylase, 33
Amyloid, 25
Amylopsin, 33
Anabiosis, 66
Anabolism, 43, 46, 57, 68

vagus, 332
Anaemia, 100

pernicious, 539
Anaerobic organisms, 68
Anaesthetics, 53 ,
Anelectrolytes, 142
Anhydraemia, 143
Animal gum, 130
Animals, characters, 19, 53
Annulus of Vieussens, 328, 354
Anterolateral nucleus, 363
Anti-coagulants, 124
Anti-kinase, blood, 128, 140
A nti- thrombi n, 140
Aorta, pressure, 208
Apex beat, 221
Apnoea, birds, 484

experimental, 475

2 o

561

562

PHYSIOLOGY

Apnoea, foetal, 477

true and false, 477

vagi, 479, 488

voluntary, 480
Arginase, 33
Arginine, 27, 33
Argon, blood, 387
Arteria aspera, 159

venosa, 159
Arterial pressure, 241, 243, 253

pressure, pulmonary, 254

pulse, 263

tone, 346
Arteries, locomotion, 245, 277

pressure, 241, 243, 253

suspension, 245

tone, 346

velocity in, 256
Asparagine, 60
Asphyxia, 380, 469
Aspiration, diastolic, 208, 210

systolic, 208
Assimilation, 86
Atelectasis, 405
Atmosphere, gases, 397
Atmospheric pressure, 72
Atropine, secretion, 522
Auditory nerve, respiration, 465
Auricles, 180

pressure in, 203

septum, 299
Auriculo-ventricular bundle, 315

valves, 192
Auscultation, heart, 196

lungs, 426
Autolysis, 34
Automatic control, heart, 210

respiration, 461
Automaticity, heart, 298, 305

respiration. 457, 480

vascular rhythm, 343

vital, 83, 85

Autonomous metabolism, 86
Autosphygmogram, 265
Auxocardia, 186, 215, 226

Bacillus butyricus, 37
Bacteria, metabolism, 61, 65

nitrifying, 58
Bacteriolysis, 154
Bacterium lacticum, 37

photometricum, 78
Barometric pressure, blood, 384

respiration, 474
Barotaxis, 76
Bathmotropism, 327
Benthos, 82
Bilirubin, 109
Biogen hypothesis, 88
Biogenesis, 2
Biology, scope 1

marine, 81
Biometry, 48

Biomorphosis, 49
Biotouus, 88
Biuret test, 22
Blood, alexines, 154

alkalimetry, 96

asphyxia, 380

bactericidal properties, 154

bufFy coat, 97

circulation, 157

coagulation, 97, 132

corpuscles, 91, 100, 113, 117

defibrinated, 97

enzymes, 127

erythrocytes, 100

examination, 120

gases, 132, 379, 384, 388, 474

immunity, 154

leucocytes, 113

lymph, 512

metabolites, 129

peptone, 124

physical properties, 94

plasma, 123

platelets, 117

pressure, 238, 281

pressure in arteries, 241

pressure in capillaries, 253

pressure in veins, 253

quantity, 98

reaction, 94

respiratory rhythm, 490

specific gravity, 95

spectra, 110

stream, 232

toxicity, 153

transfusion, 152

velocity in arteries, 256, 261

velocity in capillaries, 263, 281

velocity in veins, 262, 281

vessels, 343

viscosity, 151
"Blut-schatten," 106
Bridge, Wheatstone's, 150
Bronchi, 403
Bronchial murmur, 427

muscle and nerves, 442
Buffy coat, 97
Bulbar centres, respiratory, 450

vasomotor, 361
Bulbus arteriosus, 187
Bundle, auric ulo- ventricular, 314
Butyric fermentation, 37

Calcium, coagulation, 136
Canaliculi, lymphatic, 509
Cannula, perfusion, 288, 289
Capacity, vital, 423
Capillaries, blood, 172

blood, area, 263

blood, pressure, 253

blood, velocity in, 263

lymphatic, 507
Caproic acid, 35

INDEX OF SUBJECTS

563

Carbohydrates, 36

in blood, 130

metabolism, 59

respiratory quotient, 399
Carbon dioxide, elimination, 391

of blood, 385

output, 470

Carboxy- haemoglobin, 110
Cardiac cycle, 205

ganglia, 299

muscle and nerves, 285

nerves, depressor, 360

nerves, sympathetic, 327

nerves, vagi, 322

reflexes, 333
Cardiograms, 223, 268
Cardiograph, 222
Cardio-pneumatic movement, 227
Caseinogen, 23, 40
Caseose, 23
Catalases, 34
Catalysators, 31
Catalysis, 31

Catheter, pulmonary, 388
Cell, 8, 13, 16

chemistry of, 19, 20, 37

colony, 15

theory, 12
Cells, giant, 535

marrow, 538

splenic, 549

Traube, 147
Cellulose, 37
Centres, cardiac, 336

expiratory and inspiratory, 454

germinal, 529

nerve, oxygen, 394

respiratory, bulbar, 443

respiratory, cerebral, 452, 464

respiratory, spinal, 451

splenic, 554

vasomotor, bulbar, 361

vasomotor, spinal, 362, 364
Centrifuge, 98
Centrosome, 13
Cerebrin, 35
Chemomorphosis, 49
Chemotaxis, 74

leucocytes, 178
Chest, cavity, 407
Cheyne-Stokes respiration, 492
Chitin, 37

Chloral, respiration, 455
Chlorophyll, 18, 58
Chloroplasts, 59
Cholesterin, 36, 130
Chondrioderma, 16
Chorda tympani, vasodilatation, 350

tympani, lymph, 522
Chromoproteins, 23
Chronotropism, vagus, 325
Chyle, 512
Chymosin, 33, 128

Circulation, blood, discovery, 157

dynamics, 233

intrathoracic pressure, 406, 436

lymph, 515

time, 282

Clostridium Pasteurianum, 57
Clupeine, 24
Coagulation, by enzymes, 33

by heat, 21

of blood, 97, 132

of lymph, 513

of milk, 135
Cocaine, bulb, 450

protoplasm, 102
Collagen, 23, 25
Colloids, 21
Colpidium colpoda, 66
Complemental air, 423
Concentration, molecular, 141
Conchiolin, 25

Conditions of activity, heart. 292
Conductivity, electrical, plasma,

149

Conjugated proteins, 23
Conservation, of energy, 5

of matter, 5

Coronary circulation, 210
Corpora Arantii, 187
Corpuscles, blood, 91, 100, 113

lymph, 513

Malpighian, 547

marrow, 535
Crassamentum, 97
Creatine, 35, 129
Creatinine, 35
Crusta phlogistica, 97
Crying, 438
Cryoscopy, 142, 148
Crystalloids, 21
Cube, Schultz, 111
Cycle, cardiac, 180
Cysteine, 27
Cystine, 27
Cytoglobulin, 140
Cytoplasm, 13
Cytosine, 24

Darwinism, 47
Death, apparent, 66
Delirium cordis, 321
Denaturation, protein, 21
Depressor nerves, 333, 360
Descent, doctrine of, 8
Desiccation and revival, 66
Deutoplasm, 35
Dextrose, 36

Diamino-trioxy-dodecanic acid, 27
Diapedesis, 115
Diaphragm, 410, 417
Diastases, 33

blood, 127
Diastole, 180, 208

active, 208

564

PHYSIOLOGY

Diastole, aspiration, 208, 210

vagal, 325
Dicrotism, 265
Differentiation, 91
Diffusion, gas, 378
Digestion, plant, 54
Dilatator nerves, 350
Dionaea nmscipula, 53
Di-saccharides, 37
Dissimilation, 86
Dissociation, ionic, 142

oxyhaemoglobin, 395, 401
Docimasia hydrostatica, 405
Dromorneters, 257
Droinotropism, sympathetic, 330

vagal, 326

Drosera rotundi folia, 54
Dualism, 6

Duct, thoracic, 506, 512
Dynamics, circulation, 233
Dyspnoea, 403, 468

compensatory, 480

febrile, 469

post-apnbeic, 481

thermal, 470

vagotomy, 458, 468

venosity of blood, 469

voluntary, 482

Ear, vasomotor nerves, 343
Ectoplasm, 17
Eddies, arterial, 189
Effusions, serous, 515
Elastic tubes, flow, 239
Elasticity, blood-vessels, 239
Elastin, 23, 25
Electrical conductivity, 149

convection, 90

stimuli, 80

variations, heart, 332
Electrolytic dissociation, 142
Embryo, heart, 309
Embryology, 3
Emulsions, 21
Enchylema, 17
Endo-enzymes, 34
Endoplasm, 17
Endosmometer, 141
Energy, kinetic and potential, 44

conservation, 5
Enterokinase, 30
Enzymes, blood, 127

classification, 31

properties, 29
Erepsin, 32, 34
Erythroblasts, 535
Erythrocytes, blood, 100, 146

lymph, 513
marrow, 535

nucleated, 536
Eudorina, colony, 15
Eupnoea, 403, 467
Eustachian valve, 182

Evolution, 46
Exchange, gas, 375, 387
Excitability, 44

heart, 313
Expiration, 419
Expiratory centres, 454
Expired air, 397
Exploring sound, cardiac, 200

sound, oesophageal, 228, 406, 429

sound, rectal, 429
Extraction, gas, 377
Extra-systole, 320

Facial nerve, vaso-constriction, 348
Fatigue, 73
Fats, cell, 35

plasma, 130

respiratory quotient, 399
Femoral sphygmogram, 270
Ferment, fibrin, 128
Ferments, 21, 39
Ferric album inate, 551
Fibrin, 97

ferment, 129, 137
Fibrinogen, 125, 128
Fibrinoglobuliu, 135
Fibroin, 25

Filtration, lymph, 521
Fistula, lymphatic, 512

pericardial, 215
Foetus, apnoea, 477

lung, 405
Follicles, agminated, 530

solitary, 529

Formatio reticularis, 445
Frog, heart, 286

nerves of heart, 328
Fructose, 36

Fumaria hygrometrica, 59
Fungi, 57
Funiculus solitarius, 445

Galium aparina, 79

Galvanotaxis, 80

Ganglia, heart, 299

Ganglion, Gasserian, 328, 354

"Gas silvestre," 371

Gases, absorption and diffusion, 378

atmospheric, 397

blood, 379, 384, 388

extraction, 382

lymph, 514

plasma, 132

physics, 378

protoplasm, 38

respiratory, 387
Gasometric apparatus, 484
Gelatin, 23
Gelatose, 23
Geomorphosis, 49
Geotaxis, 77
Giant cells, 535
Glands, haemolymphatic, 557

INDEX OF SUBJECTS

565

Glands, lymphatic, 530

submaxillary, 343
Gliadins, 23
Globulins, 23

serum, 126, 128
Globulose, 23

Glosso - pharyngeal nerve, circulation,
360

respiration, 465
Glottis, respiration, 421
Glucoproteins, 23, 25
Glucosamine, 27
Glucose, 36

blood, 130
Glutaminic acid, 27
Glutelins, 23
Glycine, 27
Glycogen, 18, 37

blood, 130

Glycolysis, blood, 127
Gly co proteins, 23
Glycyl-glycine, 28
Glycyl-tyrosine, 23
Granules, leucocytes, 114

protoplasm, 17
Gum, animal, 130
Gums. 37

Haemacytometers, 102
Haemapoiesis, medullary, 534, 538

splenic, 550
Haematin, 108
Haematoblasts, 118
Haematocrite, 104, 148
Haematoidin, 109
Haematoporphyrin, 109
Haemautograph, 265
Haemin, 108
Haemochromogen, 108
Haemodiastase, 127
Haemodromograph, 257
Haemodromometers, 257
Haemodynamics, 233
Haemoglobin, 105, 107, 109

carbon dioxide, 386

derivatives, 108

oxygen, 383

Haemoglobinometer, 121
Haemoglobinuria, 153
Haemolymphatic glands, 557
Haemolysis, 105, 143, 154

splenic, 550
Haemorrhage, 152
Haemotachometer, 274
Heart, anatomy, 182

apparatus, 287

automatic regulation, 210

automatism, 298, 305

block, 315

cycle, 180

delirium of, 321

embryo, 309

frog, 286

Heart, ganglia, 299

impulse, 221

inhibition, 322

inhibition, reflex, 336

intrathoracic pressure, 436

intrinsic nerves, 299

invertebrate, 311

ligature, Stannius, 299

limulus, 311

locomotion, 224

mechanics, 180, 187, 190, 201

myo- and neurogenic theories, 307,
308, 310

nerves, accelerator, 327

nerves, depressor, 333

nerves, inhibitory, 322

oxygen, 293

perfusion, 289

phases of Luciani, 302

plethysmograms, 216

refractory period, 320

resuscitation, 298

rhythmicity, 298, 322

self- steering action, 210

sounds, 196, 198

staircase, 318

survival, 298

tonicity, 319

tortoise, 286

urea, 297

valves, 187, 190

volume changes, 215

work, 230
Hearts, lymph, 516
Heat, death, 71

stimulus, 77
Heliotaxis, 78

Hemiplegia, respiratory, 444, 452
Heredity, 49
Heterogenesis, 52
Hibernation, respiration, 496
High altitudes, blood, 384
Hippuric acid, 129
Histidine, 27

Histogenic substances, 126
Histolytic substances, 93, 126
Histones, 23, 24, 106, 117
History, circulation, 157

respiration, 369, 402
Hyaloplasm, 17
Hydraemia, 143, 152
Hydrobilirubin, 110
Hydrodynamics, circulation, 232
Hydrogel, 21
Hydrogenase, 34
Hydrolysis, 26, 32
Hydromorphosis, 49
Hydi-osol, 21
Hyperaemia, active, 341

paralytic, 345
Hyperpnoea, 469

Hypoglossal nerve, vasomotors, 348
Hypoxanthine, 24, 35

566

PHYSIOLOGY

Ichthulin, 2-3
Ictus cordis, 222
Idioplasm, 50
Immunity, 154
Impulse, heart, 221
Inanition, 65
Inflammation, 176
Infundibula, lung, 403
Inhibitory centres, heart, 336

centres, respiration, 452

nerves, heart, 322
Inorganic constituents, cell, 37

constituents, serum, 131
Inotropism, heart, 326, 330
Inspiration, 409
Inspiratory centres, 454

muscles, 409

Intercartilaginous muscles, 414
Intercostal muscles, 411
Intermolecular oxygen, 394
Internal respiration, 375
Intersystole, 201
Intra-abdomiiial pressure, 427
Intracardiac pressure, 201
Intrapleural pressure, 428
Intrapulmonary pressure, 405, 424
Intrathoracic pressure, 406, 427, 436
Inversion, sugars, 37
Invertase, 33
Invertebrate heart, 311
Ions, 32
lonisation, 142
Iron, haemoglobin, 108

metabolism, bacteria, 65

spleen, 551

Ischaemia, active, 342
Isoleucine, 27
Isotony, 142

Jecorin, plasma, 130

Kata-, vide Cata-
Katabolism, 43
Keratin, 25
Kinase, blood, 139
Kinases, 30
Kinetic energy, 44
Knephoplankton, 83
Kymograph, 242

Lactacidase, 34

Lactase, 34

Lacteals, 171

Lactose, 37

Laevulinic acid, 24

Laevulose, 37

Lamarckism, 48

Laryngeal nerves, respiration, 465

Larynx, respiration, 419, 421

Latent life, 65

systole, 206

Laughter, mechanism, 438
Laws of gases, 378

of solutions, 141

Laws of variation, 48
Lecithin, 35, 130
Leech, coagulation, 124
Leucaemia, 116
Leucine, 27
Leucocytes, blood, 113

chemistry, 117

chemotaxis, 116, 178

coagulation, 138

diapedesis, 115

lymph, 513

marrow, 534

movement, 115

narcosis, 178

origin, 114

phagocytosis, 115
Leucocytosis, 152
Leuconuclein, 138
Leucyl-glutamic acid, 23
Levatores costarum, 410
Life, minimal, 67

physical basis, 11

potential, 65

pressure, 71

temperature, 70
Light, a stimulus, 78, 81
Limbs, vasomotor nerves, 349, 354
Limulus, heart, 311
Lipase, 33

blood, 127
Locomotion, arteries, 277

heart, 224
Lungs, foetal, 405

gas exchange, 387

movements, 426, 442

structure, 403

ventilation, 423, 484, 487
Luxus respiration, 473
Lymph, 505

blood-, 512

cells, 513

circulation, 515

composition, 513

nitration, 521

formation, 519

gas, 514

hearts, 516

injection of, 533

liver, 514

post mortem, 515

quantity, 514

secretion, 519

sources, 512

tissue-, 512

transudation, 524

velocity, 516
Lymphagogues, 523
Lymphatic, canaliculi, 509

cavities, 514

fistula, 513

pressure, 516

stomata, 510

system, 505

INDEX OF SUBJECTS

567

Lymphatic vessels, 506
Lymphatics, perivascular, 507
Lymphocytes, 114, 513, 529
Lymphoid follicles, 529

tissue, 528
Lysine, 27

Macrocytes, 101
Maltase, 33
Maltose, 33
Manometer, elastic, 244

maximum and minimum, 207

mercury, 244
Marine organisms, 81
Marrow, 534

cells, 535

haemapoiesis, 538

phagocytosis, 537
Materialism, 5
Matter, conservation, 5

inorganic, organism, 37

inorganic, serum, 131
Mechanical stimuli, 76
Mechanics, heart, 180

respiration, 402
Mechanism, protoplasmic, 85
Mechanomorphosis, 49
Medulla oblongata, blood-vessels, 361

heart, 336

respiration, 443
Megacaryocytes, 535
Meiocardia, 186, 215
Melanins, 25
Membrane, cell, 13

semi-permeable, 141
Merotomy, 12
Metabolism, allonomous, 87

autonomous, 86

in animals, 42, 61

in plants, 54

in saprophytes, 60

of mineral matter, 62

splenic, 552

Metabolites, protein, 35, 129
Metaglobulin, 125
Metaprotein, 23
Metazoa, 11
Methaemoglobin, 125
Microcytes, 101
Migratory cells, 175
Milk, -clotting, 135
Mimosa pudica, 53
Mineral matter, cell, 37

matter, metabolism, 62

matter, serum, 131
Mitral valve, 190
Molecular concentration, 141
Monism, 6
Monosaccharides, 36
Morphology, 2
Mosquitoes, coagulation, 124
Motor nerves, respiration, 441
Mountain sickness, 474

Movements, amoeboid, 16, 74, 115

arterial, 277

cardiopneiimatic, 227

pulmonary, 426, 442
Mucoid, serum, 126
Murmurs, bronchial, 427

cardiac, 198

vesicular, 427
Muscle, bronchial, 442

cardiac, 285

respiration of, 394

sound of, 197

vascular, 427
Muscles, expiratory, 419

inspiratory, 409

of neck, 410

of thorax, 412
Muscular dyspnoea, 471
Mutation, 51
Myocardium, 182, 312

conductivity, 313

excitability, 313
Myogenic theory, heart, 307
Myosin, 23
Myosinogen, 23
Myxomycetes, protoplasm, 15

Nagelism, 49

Narcosis, leucocytes, 178

Nasal mucosa, respiration, 465

Nasal respiratory movements, 422

Neo-Darwinism, 47

Neo-Lamarckism, 49

Neo-vitalism, 5

Nepenthes, 55

Nerve cells, survival, 310

Nerves, afferent cardiac, 333, 360

afferent, respiratory, 457

bronchial, 442

efferent cardiac, 322, 327

efferent lymphatic, 517

efferent, respiratory, 441

neck, rabbit, 334

respiratory exchange, 392

secretory, 522

submaxillary gland, 343, 522

vasomotor, 341
Nervi erigentes, 355
Neurogenic theory, heart, 310
Nitrifying bacteria, 57
Nitrogen, 372

blood, 377, 386

expired air, 397
Nodulus Arantii, 187
"Nceud vital," 444
Non-electrolytes, 142
Nucleic acid, 24

acid, coagulation, 138
Nuclein, 23, 35, 49
Nucleohistone, 138
Nucleolus, 39
Nucleoproteins, 23, 24
Nucleus, anterolateral, 363

568

PHYSIOLOGY

Nucleus cell, 13

cell, chemistry, 39

cell, structure, 19
Nutrition, 64

Occlusion of trachea, 460

Octadecapeptide, 29

Oedema, 520

Oenothera, 52

Oesophageal sound, 429

Olfactory nerves, respiration, 465

Oligocythaemia, 152

Ontogeny, 2, 46

Optic nerve, respiration, 465

Optical activity, protein, 21

Organisms, elementary, 11

aerobic, 68

anaerobic, 68
Osazones, 37
Osmotic pressure, blood, 142

pressure, fish, 145

pressure, lymph, 515

pressure, serum, 147
Ovalbumin, 23
Ovomucoid, 126
Oxalates, coagulation, 125
Oxidases, 33
Oxygen, absorption, lung, 389

blood, 380

discovery, 372

expired air, 389, 397

haemoglobin, 383

heart, 293

intermolecular, 394

life, 68

nerve centres, 394
Oxy haemoglobin, 106

dissociation, 395
Oxyproline, 27
Oxypyrrolidine-carboxylic acid, 27

Palaeontology, 2

Pancreas of Aselli, 533

Panteplankton, 83

Papain, 32, 54

Paracasein, 136

Paraglobulin, 126

Paralysis, 73

Paramoecium, galvanotaxis, 80

geotaxis, 77
Parasites, 60

Partial pressure, respiration, 389
Patches of Peyer, 530
Pause, cardiac, 180

respiratory, 499
Pentoses, 24
Pepsin, 32
Peptones, 23
Percussion, lungs, 425
Perfusion, 289
Pericardium, fistula, 209, 215

pressure, 219

Periodic respiration, 492, 494

Peripheral stream, 189

Perisystole, 180

Perivascular lymphatics, 507

Pernicious anaemia, 539

Peroxidases, 33

Phagocytes, 18, 115, 178, 537

Phaoplankton, 83

Phases, heart, Luciani's, 302

Phenomena, objective and subjective, 6

psychical. 7

vital, 1, 42
Phenomenalism, 7
Phenyl-alanine, 27
Phenyl-glucosazone, 37
Phenyl-hydrazine, 37
Phlebograms, 204
Phlogiston, 373
Phlogosin, 178
Phosphates, cell, 48
Phosphoproteins, 23, 24
Phosphorus, reaction, 39
Photomorphosis, 49
Phototaxis, 78
Phrenic nerves, 441
Phrenograph, 416
Phylogeny, 2, 46
Physical basis of life, 11
Physiology, scope, 3
Piezometer, 233
Pigments, 25

" Pince cardiographique," 289
Pinocytosis, 534
Pitot tubes, 234
Plankton, 82
Plants and animals, 53, 55

insectivorous, 53
Plasma, blood, 123, 142

carbohydrates, 130

electrical conductivity, 144, 149

fats, 130

gas, 132

histogenic matter, 93, 126

histolytic matter, 93

incoagulable, 124

inorganic matter, 131

molecular concentration, 141

osmotic pressure, 142

proteins, 125, 126

viscosity, 151

lymph, 513
Plasmodium, 113
Plateau, systolic, 206
Platelets, blood, 117

blood, coagulation, 134
Plethora, 100
Plethysmograms, 216, 279
Plethysmographs, 278, 344
Pleura! cavity, 403, 425
Pluralism, 7
Pneumograph, 415
Pneumoplethysmograph, 425
Pneumothorax, 406

INDEX OF SUBJECTS

569

Poikilocytes, 101
Polycythaemia, 153
Polypeptides, 23, 28
Polypnoea, 470
Polysaccharides, 37
Post-mortem lymph, 515
Potential energy, 68
Pressure, alveolar, 405, 424

arterial, 241, 243, 253

capillary, 253

intra-abdominal, 427

intracardiac, 201, 208

'intrathoracic, 406, 427

lymphatic, 513, 516

osmotic, 141

pericardial, 219
Presystole, 180
Pro-enzymes, 30
Proline, 27
Propeptones, 23
Prosthetic group, protein, 24
Protagon, 35
Protamines, 23, 24
Proteins, 20

classification, 23

cleavage, 26, 28

coagulation, 21

conjugated, 23, 24

of plasma, 125, 126

properties, 21

reactions, 21, 22

respiratory quotient, 399

structure, 25
Proteoses, 23
Prothrombin, 137
Protista, 13
Protistology, 3
Protoplasm, 17, 18

myxomycetes, 15
Protozoa, 11
Pseudopodia, 16
Ptyalin, 33
Pulmonary arterial pressure, 254

catheter, 388

circulation, discovery, 160

epithelium, absorption, 391

gas exchanges, 387
Pulp, splenic, 547
Pulse, arterial, 263

cardiac, 221

negative cardiac, 227

negative pulmonary, 227

negative thoracic, 227

negative venous, 203, 227

wave, 240, 271
Purine, 24
Pus, 115
Pycnometer, 95
Pyrimidine, 24

Quantity of blood, 99

of lymph, 514
Quotient, respiratory, 398

Radial sphygmogram, 264
Radiolaria, 14
Reaction of blood, 94

of lymph, 513
Reactions of carbohydrates, 36

of proteins, 21
Receptaculum Chyli, 517
Rectal sound, 429

Red blood corpuscles, vide Erythrocytes
Reductase, 34

Reduction, by carbohydrates, 36
Reflexes, cardiac, 336

respiratory, 464

vascular, 357

Refractory period, heart, 320
i Regeneration, 84

blood, 152
Reproduction, 43
Reserve air, 423
I Residual air, 423
Resistance capacity, 150
Respiration, abdominal, 416

adaptation, 469

afferent nerves, 457

chemistry and physics, 369

Cheyne-Stokes, 492

efferent nerves, 441

external, 376

internal, 375, 393

luxus, 472, 473

mechanics, 402, 433

nerve centres, 394

nervous control, 440

periodic, 492

rhythm, 437, 440
Respiratory centres, 443, 451, 452, 464

centres, expiratory, 454

centres, inhibitory, 452

exchanges, 379, 392

hemiplegia, 444

movements, 416

pause, 499

pressures, 429

quotient, 398

quotient, carbohydrates, 399

quotient, fats, 399

quotient, proteins, 399
Revolution of heart, 180
Rheotaxis, 76
Rhizobium, 58
Rhizopoda, 13
Rhythm, heart, 333

respiration, 437, 440

respiration, automaticity, 461

respiration, control, 440

respiration, periodic, 492
Rhythmicity, heart, 298, 322
Ribs, 408

Saccharomyces cerevisiae, 30, 60
Saccharoses, 37
Salmine, 23
Salts, 37

570

PHYSIOLOGY

Salts, heart, 295

Saprophytes, 57, 69

Sarkine, 35

Scalene muscles, 410

Schizomycetes, 57

Sciatic nerve, vaso-constrictors, 351

Sclero-proteins, 23, 25

Scombrine, 24

Scotoplankton, 83

Secretion, and lymph formation, 522

of lymph, 519
Selection, germinal, 50

natural, 46

Self-steering action of heart, 210
Semilunar valves, 187
Semipermeable membranes, 141
Sensations, 6, 45
Sensibility, 45
Sensitive plants, 53
Septum, auricular, 299
Serin, 126
Serine, 27
Sero-mucoid, 126
Serous cavities, 514

effusions, 515
Serum, 97, 127

ash, 131

carbohydrates, 130

conductivity, 150

enzymes, 127

fats, 127

measurement of osmotic pressure,
144, 147

toxicity, 153
Serum albumin, 126, 128

globulin, 126
Silkworm, 70
Sinus of Yalsalva, 187

venosus, 286
Skeleton, thoracic, 407
Sleep, 501
Sneezing, 438
Soaps, plasma, 130
Sobbing, 438
Solutions, colloid, 21

laws of, 141

normal physiological, 293
Sound, exploring, cardiographic, 200
, exploring, oesophageal, 228, 406,
429

exploring, rectal, 429

muscle, 197
Sounds, heart, 196
Spaces, lymphatic, 509
Species, 46

Spectrophotometer, 109
Sphygmograms, analysis, 271
Sphygmographs, 264
Sphygmomanometer, 245
Sphygmoscope, 205
Spinal centres, respiratory, 451

centres, splenic, 554

centres, vasomotor, 362, 364

Spiritus igneo-aereus, 372

Spiritus nitro-aereus, 372

Spirograph, 425

Spirometer, 422

Spirostomum, 81

Splanchnic nerves, blood-vessels, 348

lymph vessels, 518

respiration, 465
Spleen, 545

cells, 549

contractility, 553

extirpation, 550

haemapoiesis, 550

haemolysis, 551

lymphapoiesis, 552

metabolism, 552

nerves, 549

nerve centres, 554
Spongin, 23, 25
Staircase, heart, 318
Staphylococcus, 178
Starch, 37
Steapsin, 33
Stentor, 14

Sternum, asthma, 410
Stethograph, 415
Stimuli, 73

chemical, 73

electrical, 80

internal, 83

luminous, 78

mechanical, 76

thermal, 77
Stomata, 510

Stromata, erythrocytes, 106
Stromuhr, 257
Sturine, 23

Submaxillary gland, 343
Substances, histogenic and histolytic,

93, 126
Sugars, 36
Sulphates, 38

Sulpho-methaemoglobin, 110
Sulphur, protein, 22
Sulphur metabolism, bacteria, 65
Suppuration, 115, 178
Surface area, capillaries, 263

thoracic, 417
Survival, heart, 298
nerve centres, 310
Suspension of artery, 245

of heart, 290
Suspensions, colloid, 21
Swimming-bladder, gas of, 390
Symbiosis, 58
Sympathetic nerve, blood-vessels, 342

nerve, heart, 328
Syncytium, 15

System, circulatory, 157, 180
lymphatic, 505
respiratory, 369
vegetative and animal, 92
Systole, 185

INDEX OF SUBJECTS

571

Systole, aspiration, 208

latent, 206
Systolic plateau, 206

Tachograms, 275
Tachypnoea, 461, 470
Tambour, recording, 201
Temperature, and life, 70
Tension of gases, alveolar air, 390

of gases in atmosphere, 388

of gases in blood, 388, 389

of gases in expired air, 389
Tetanus, electrical, 80

mechanical, 76

thermal, 77
Thallassicolla, 14
Thermal dyspnoea, 470

stimuli, 77

Thermomorphosis, 49
Thermotaxis, 78
Thigmotaxis, 76
Thoracic duct, 171

respiration, 416
Thoracometer, 415
Thorax, skeleton, 407

surface area, 417
Thrombin, 137
Thrombokinase, 139
Thrombosin, 135
Thrombosis, 133
Thymine, 24
Thymus, 540

extirpation, 542

feeding, 545

structure, 541
Tidal air, 422
Tissue, lymphoid, 528
Tissues, 13

and lymph, 505

respiration of, 393
Tone, arterial, 262, 344, 346
Tonicity, heart, 319
Tonograph, heart, 288
Tonometer, arterial, 244, 252
Tortoise, heart, 286
Trachea, 403
Tradescantia, 18
Transfusion, blood, 152
Transplantations, 13
Transudation, lymph, 524
Tricuspid valve, 191
Trypsin, 32
Tryptophane, 27
Tubes, bronchial, 403

elastic, 239

Types of respiration, 416
Tyrosine, 27

Ultramicroscope, 21
Uracil, 24
Urea, 33, 35

heart, 297

plasma, 129

Urease, 33

Uric acid, 129, 552

Urobilin, 109

Vacuoles, cell, 18
Vago-sympathetic trunk, 328, 353
Vagus, apnoea, 479, 488

cardiac, 218

cardiac, anabolic action, 332

cardiac, bathmotropic effect, 327

cardiac, chronotropic effect, 325

cardiac, dromotropic effect, 326

cardiac, inotropic effect, 326

laryngeal,464

pulmonary, afferent fibres, 462

pulmonary, efferent fibres, 442

pulmonary, section of, 462
Valve, Eustachian, 182
Valves, cardiac, auriculo- ventricular,
192

cardiac, semilunar, 187

veins, 165

Variability of species, 45, 47
Variation, 47

and Quetelet's law, 48
Vaso-constrictor centres, 361

nerves, 347
Vaso-dilatator centres, 365

nerves, 350
Vasomotor centres, 361

nerves, 341

nerves, ear, 343

nerves, head and neck, 34S

nerves, limbs, 349, 354

reflexes, 357

viscera, 348
Veins, pressure in, 253

pulsation, 203

valves of, 165

velocity in, 262
Velocity, blood, 174, 263

in arteries, 256, 261

in capillaries, 263

of lymph formation, 523

in veins, 262

of lymph, 516
Vena arteriosa, 159
Venosity of blood, dyspnoea, 469
Venous pressure, 253

pulse, 203

valves, 165

Ventilation, lungs, 423, 484, 487
Ventricles, pressure in, 201

structure, 183

systole and diastole, 185
Vessels, blood, 341

lacteal, 171

lymphatic, 506
Vicia fabia, 58
Viscosimeter, 151
Viscosity, blood, 151
Vital capacity, 423
Vitalism, 5

572

Vitellin, 23
Volume, heart, 215
Voluntary apnoea, 480
Vortices, arterial, 189

Water, life, 66
Wave, pulse, 240

dicrotic, 269

velocity, 273
Work, heart, 230

PHYSIOLOGY

Xanthine, 24, 130, 298, 552
Xanthoproteic test, 22

Yawning, 438

Zea mais, 59
Zoospores, 16
Zymase, 30

blood, 127
Zymogens, 30

INDEX OF AUTHORS

ABDERHALDEN, amino-acids, 26

physiological chemistry, 39

proteins, 26

ABELOUS, thymus, 543, 557
ADAM, automatism of heart, 306

resuscitation of heart, 298
ADAMI, accelerator nerves, 329

systole, 182
ADAMKIEWICS, intrathoracic pressure,

427

ADAMS, G. P., phototropism, 90
ADAMUK, vasomotor centres, 365
ADDISON, "W., coagulation of blood, 133

diapedesis, 175
ADUCCO, active expiration, 420, 439

bulbar centres, 448, 449, 489, 504

physiology, text-book, 9

respiratory centres, 454
ALBANESE, oxygen and heart, 293

viscosity of blood, 151
ALBERTONI, accelerator nerves, 329

cocaine and protoplasm, 102

peptone blood, 124

transfusion, 153"

ALBINI, diastolic aspiration, 211
ALBRECHT, active diastole, 214
ARANTIUS, intercostal muscles, 411

nodule of, 187

ARISTOTLE, respiration, 369, 380
ARLOING, heart, 231

vagus, 324

ARNOLD, lymphatic organs, 557
ARON, intrathoracic pressure, 427
ARRHENIUS, electric conductivity, 149

ionisation, 142

solutions, 142

ARRONET, plasma and corpuscles, 125
ARRONS, isolation of heart, 291
D'ARSONVAL, expired air, 397
ARTHUS, coagulation of blood, 136

lipase of blood, 127
ASELLI, pancreas of, 533

lymphatic system, 171, 505
ASHER, formation of lymph, 526, 558

injection of lymph, 533

innervation of blood-vessels, 367

post-mortem lymph, 515

| ASHER, tissue lymph, 527 557
ASP, cardiac reflexes, 336

splanchnics, 348
AUBERT, cardiac vagus, 336

BACCELLI, heart-beat, 222

spleen, 553
BACHMAN, conditions of cardiac activity,

298, 338
BAGLIONI, apnoea, 491

nerve centres and oxygen, 394

respiratory reflexes, 466, 504

urea and heart, 297, 338
BAHR, heart-beat, 225
BAIN, spleen, 551, 558
BAINBRIDGE, post-mortem lymph, 515,

558
BALDWIN, T. INI., development and

evolution, 63
BALE AN, H., blood, 122
BAMBERGER, heart- beat, 225
BANCROFT, J. AV., galvanotaxis, 90
BARBERA, injection of lymph, 533, 557

tissue lymph, 527, 557
BARCROFT, J., blood gases, 401

blood, urea, 156

metabolism, 400, 401
BARRAL, glycolysis in blood, 127
BARRY, mechanics of thoracic move-
ments, 429
BARTHOLIN, circulation, 166

formation of lymph, 519

intercostal muscles, 411

lymphatic system, 172, 505
BARTLETT, J. H., blood pressure, 439
BASCH, thymus, 545
v. BASCH, plethysmograph, 344

sphygmomanometer, 245
BATESON, evolution, 62, 63
BAUMANN, E. P., haemorrhage, 156
BAUMGARTEN, auriculo - ventricular

valves, 192
BAXT, accelerator nerves, 330

cardiac nerves, 331, 338
BAYLE, respiration, 412
BAYLISS, W. M., acceleration of heart,
330

573

574

PHYSIOLOGY

BAYLISS, W. M., cardiac vagus, 326
caseinogen, 40

intracardiac pressure, 201, 207
systole, 206
vascular tone, 346, 368
vaso-constrictors of limbs, 349
vaso-dilatators of limbs, 354, 367
vasomotor reflexes, 368
BE ALE, coagulation of blood, 133
BEAU, heart-beat, 222

intercostal muscles, 411, 439
thoracic respiration, 417
BEAUNIS, physiology, text-book, 9
BECCARI, venous pulse, 203
BECHT, F. C., salivary glands, 558
BECHTEREW, vasomotor centres, 366
BECKMANN, cryoscopy, 148
BEHRING, bacteriolytic functions of

blood, 154

BELFIELD, vascular reflexes, 360
BELL, law of, 354
v. BENEDEX, centrosome, 13
BENEDIKT, S. K, heart, 339
BERAUD, active diastole, 213
auriculo-ventricular valves, 192
elasticity of blood-vessels, 239
BERGENDALL, intercartilaginous

muscles, 415
BERGMANN, intercartilaginous muscles,

415

respiration, 373, 400
BERKELEY, phenomenalism, 7
BERKLEY, myocardium, 314
BERKOWITSCH, vasomotor centres, 363
BERNARD, anaesthetics on animals and

plants, 53
blood pressure, 253
cardiac reflexes, 336
cardiac vagus, 323
cervical sympathetic, 341, 348
chorda tympani, 341, 350, 367
facial nerve, 348
general physiology, 89
haemodiastase, 137
sensibility and excitability, 45
tissue respiration, 394
vaso-constrictors of limbs, 349, 367
vasomotor centres, 362, 367
' vasomotor reflexes, 356
BERNS, apnoea, 485
BERNSTEIN, cardiac centres, 337
foetal lungs, 405
spirograph, 425, 439
vascular tone, 346
vasomotor nerves, 352
BERT, atmospheric pressure, 72
bronchial muscles, 442
negative pulse, 227
oxygen of blood, 384, 400
plants and oxygen, 56
rectal explorer, 429
respiratory tracings, 424
thoracograph, 415

BERT, tissue respiration, 393
BERTOLUS, velocity of blood stream,

275

BERZELIUS, blood, 94
BETHE, neurogenic theory, 310
BEUTNER, intracardiac pressure, 208
BEVER, accelerators of heart, 327

splanchnic nerve, 347, 367
BEYER, H. G., vasomotor centre, 367
BEYERINCK, nitrifying bacteria, 58
v. BEZOLD, accelerators of heart, 327
cardiac vagus, 324, 336, 337
splanchnic nerve, 347, 367
vascular reflexes, 359, 367
vasomotor centres, 362, 367
Avater content of organism, 38
BIAL, haemodiastase, 127
BICHAT, animal and vegetable life, 91
cardiac ganglia, 299
cardiac diastole, 208
lymph, 509
BIDDER, cardiac ganglia, 299, 305

cardiac vagus, 333

BIEDERMANN, invertebrate heart, 311
BIELETZKY, experimental a.pnoea, 484
BILLARD, thymus, 543, 557
BIOT, periodic respiration, 502
BISCHOFF, quantity of the blood, 99

respiration, 377
BIZZOZERO, blood-platelets, 118
coagulation of blood, 134
giant-cells, 535
haemorrhage, 152, 539
lymphatic canaliculi, 511
marrow, 534, 557
serous cavities, 511
spleen, 550, 552
BLACK, respiration, 373, 400
BLACKMAN, J. K., auricular rhythm,

339

BOCHEFONTAINE, vasomotor centres, 365
BOCKER, respiratory centres, 453
BOERHAAVE, intercostal muscles, 411
BOHM, accelerators of heart, 329
lymph follicle, 532
marrow, 536
solitary follicles, 529
thymus, 541

BOHR, blood gases, 383, 386, 390, 400
carbon dioxide and haemoglobin, 386
oxyhaemoglobin, 395, 396
BORDET, chemotaxis, leucocytes, 75, 178
BORDONI, experimental apnoea, 484
periodic respiration, 494, 502, 504
BORELLI, intercostal muscles, 403, 411

respiration, 439

BORUTTAU, nervous mechanism of re-
spiration, 504
BOTAZZI, embryonic heart, 309, 321,

337
osmotic pressure of blood, 144, 145,

155
physiological chemistry, 39

INDEX OF AUTHOKS

575

BOTAZZI, tonicity of heart, 319

viscosity of blood, 151, 155
BOTKIN, spleen, 553
BOTSCHETSCHKAROFF, spleen, 555
BOTTGER, test for sugar, 36
BOURDON, manometer, 277
BOUSSINGAULT, animals and plants, 55
BOVERI, centrosome, 13
BOWDITCH, cardiac accelerators, 329

preparation of, 295, 303, 317, 337

staircase phenomenon, 318

vasomotor nerves, 352
B&YCOTT, A. E., respiration, 439
BOYLE, law of, 378

respiration, 371, 378, 400
BRACKET, active diastole, 213
BRADFORD, vascular reflexes, 357

vaso-constrictors of limbs, 349

vaso-dilatators of viscera, 355
BRANDE, gas extraction, 377
BRANTLECHT, proteins, 40
v. BRASOL, formation of lymph, 525
BRAUER, centrosome, 13
BREDIG, catalysators, 31, 40
BREFELD, heat, B. Anthracis, 71
BREUER, respiratory rhythm, 459

inspiratory centres, 456, 503
BRODIE, T. G., bronchial muscle, 504

heart, 338

metabolism, 401

perfusion. 339

pulmonary vasomotors, 368

serum injections, 156
BROWN, bronchial nerves, 442

blood pressure, 245
BROWN, A. E., specific characters, 63
BROWN, 0. H., blood pressure, 284
BROWN-S^QUARD, cardiac vagus, 323,
333

cervical sympathetic, 342, 367

experimental apnoea, 476

respiratory centres, 444, 452, 504

toxicity of expired air, 397

vascular reflexes, 357

vasomotor centres, 364
BRUCKE, blood plasma, 123

coagulation of blood, 133

elementary organisms, 8

heart, self-steering, 210

intercostal muscles, 412

lymphatic glands, 533, 557

semilunar valves, 187

spleen, 553
BRUGH VAN DEII, intrathoracic pressure,

427

BUCHANAN, coagulation of blood, 134
BUCHNER, ferments, 30

tissue respiration, 393

zymase, 34

BUCHNER, H., alexines, 154
BUDGE, cardiac nerve centres, 336

cardiac vagus, 322, 335, 337

cervical sympathetic, 348

BUDGE, neurogenic theory, 307

vasomotor centres, 365
BUDGETT, galvanotaxis. 80
BUFALINI, heart, accelerators, 329
BUFFON, animals and plants, 1
BUGARSKY, serum, osmotic pressure,

144
BUGLIA, non-coagulable plasma, 124,

155
BUISSON, arterial pulse, 265

negative pulse, 227

plethysmograph, 278
BULGAK, spleen centres, 554
BUNGE, blood plasma, separation, 125

plasma ash, 131
BUNSEN, absorption of gas, 378

partial pressure, 379
BURCKHARDT, plasma, 126
BURDACH, heart-beat, 222

intercostal muscles, 411
BURDON-SANDERSON, cardiograph, 267

sphygmograph, 267

stethograph. 415

BURKART, expiratory rhythm, 486
BuRTON-C-PiTZ, R., blood, viscosity, 156

venous flow, 284

venous pressure, 284
BUTSCHLI, cell, bacteria, 13

cell, structure, 17, 19

CABMAN, A. W., cardiac nerve fibres,
338

respiratory nerve fibres, 338
CAMIS, J.. blood, dissociation curve,

401

CAMUS, lymphatic vessels, 517, 557
CALORI, venous valves, 165
CANNANUS, venous valves, 165
CARBONE, coagulation of blood, 155

fibrin ferment, 128
CARDARELLI, cardiac vagus, 323
CARLILE, heart-beat, 224

cardiac systole, 186
CARLSON, A. J., haemolytic lymph, 559

heart, inhibition, 339

heart, invertebrate, 339, 340

heart, refractory period, 339

lymph formation, 526, 559

neurogenic theory, 311, 337

salivary glands, 558

vasomotor nerves, 354, 368
CARNOY, structure of protoplasm, 17
CARPENTER, active diastole, 214
CARSWELL, heart-sounds, 196
CASPARI, acapnia, 475, 504
CASTELL, oxygen and heart, 293
CAVANI, vascular reflexes, 358, 367
CAVAZZANI, E., haemodiastase, 127

red blood-corpuscles, 101
CAVENDISH, composition of water, 374
CECCHINI, splenectomy, 557
CERADINI, auxocardia and meiocardia,
186, 227

576

PHYSIOLOGY

CERADINI, circulation of blood, 161, 179

diastolio aspiration, 212

heart, self-steering, 211

semilunar valves, 187, 231
CERVESATO, thynms, 545
CESALPINUS, circulation, 163

respiration, 371
CESARIS DEMEL, red blood-corpuscles,

ioi

CHAHCOT, vasomotor centres, 365
CHAUVEAU, auriculo-ventricular valves,
193

cardiac sound, 201

haemodromograph, 211, 274

heart, 231

heart-beat, 225

iiitersy stole, 196, 201

intracardiac pressure, 201, 206

sphygmoscope, 244

systolic aspiration, 210

velocity of blood stream, 274
CHELIUS, plethysmograph, 278
CHEVHEUL, blood, 94
CHEYNE, periodic respiration, 492
CHORIOL, active diastole, 213
CHRISTIANI, cerebral respiratory centres,

453

CHUN, Valdivia expedition, 81
CIAMICIAN, sero-mucoids, 126
CIGNA, respiration, 373
CLARKE, antero-lateral nucleus, 363
CLARKE, T. W., sulph- haemoglobin,

122
COATS, diastole, 209,

cardiac vagus, 325, 338
COHNHEIM, J., diapedesis, 115. 175

leucocytes, 115

lymph formation, 524

splanchnic nerve, 348
COHNHEIM, 0., erepsin, 32, 34
COHNSTEIN, lymph formation, 524, 557
COLASANTI, dyspnoea, 470

lactic acid in urine, 470
COLE, proteins, 40
COLIN, intracardiac pressure, 208
COLOMBO, blood pressure, 248, 256
COLUMBUS, REALDUS, circulation, 160
CONCATO, cardiac vagus, 323
CONKLIN, E. S., mutation, 63
CONNSTEIN, fats and blood, 127
CONSIGLIO, depressor nerve, 335

vascular reflexes, 356
COOPER, capillary circulation, 172
CORRIGAN, heart-beat, 222
COSSY, vaso-dilatators, 354
CRAMER, W., protagon, 40
CRAMPTON, H. E., adaptation, 63
CREDE, splenectomy, 555
CUBONI, evolution, 52
CUFFER, periodic respiration, 494
CULLIS, W. C., perfusion, 339
CUSANO, arterial pulse, 264
CUSHNY, A. R., heart rhythm, 231

CUVIER, animals and plants, 53

.intercostal muscles, 411
CYON, accelerator nerves, 327, 337

cardiac nerves, 337

depressor nerves, 333, 360

splanchnic nerves, 347

vaso-constrictor nerves, 349

vasomotor centres, 366
CZERMACK, cardiac vagus, 224
CZERNY, splenectomy, 555

DAKIN, H. D., oxidation of ammo-acids,
40

oxidation of fat, 41

DALAND, molecular concentration, 148
DALE, H. H., galvanotaxis, 90
DALLY, J. F. H., diaphragm, 439
DALTON, diffusion of gases, 378
DANILEWSKY, injection of marrow and
spleen, 539, 558

vasomotor nerves, 365
DARBISHIRE, A. D., heredity, 63
DARCY, hydrodynamics, 189
DARWIN, doctrine of descent, 46, 62

insectivorous plants, 53
DASTRE, coagulation of blood, 137

cervical sympathetic, 349, 353, 367

extra-systole, 321

splenectomy, 555, 558
vascular rettexc

iexes, 361

vasomotor nerves, 353, 366
DAVENPORT, C. D., evolution, 63
v. DAVIDOFF, marrow, 536

thymus, 541

DAVIS, B. F., lymph, 559
DAVY, H., extraction of gas, 177

residual air, 423
DAVY, J., blood gases, 377
DAWSON, P. M., blood pressure, 284
DEAHNA, vasomotor centres, 366
DEITERS, formatio reticularis, 446
DELAGE, Y., evolution, 62
DELEZENNE, anti-kinase, 128

coagulation of blood, 139
DENCKE, resuscitation of heart, 298
DENYS, lymphatic organs, 557
DETTO, evolution, 62
DEW-SMITH, heart of invertebrates, 311
DIEMERBROCK, intercostal muscles, 411
DINEUR, galvanotaxis, 81
DITTMAR, vasomotor centres, 363, 364
DIXON, W. E., bronchial muscle, 504

heart, 401

pulmonary vasomotors, 368
DOGIEL, heart-sounds, 197

serous cavities, 509

vascular reflexes, 360

velocity of blood stream, 260
DONDERS, acceleration of heart rhythm,
181

auriculo-ventricular groove, 314

cardiac vagus, 324

diastolic aspiration, 211

INDEX OF AUTHOKS

DONDERS, expiration, 419

intrapulmonary pressure, 405

human physiology, 231

lungs during respiration, 425

mechanics of thoracic movements, 424,
436

surface of thorax, 417

waves, 241

DOUGLAS, circulation of blood, 160
DOUGLAS, C. G., Cheyne-Stokes breath-
ing, 504

quantity of blood, 122

regulation of respiration, 504
DOYON, accelerators of heart, 327

lipase of blood, 127

nerves of neck, rabbit, 334
DRECHSFELD, cardiac vagus, 336
DROSDOFF, spleen, 555
DRUMMOND, haemolymphatic glands,

557

Du BOIS-REYMOND, E., dualism, 6
Du BOIS-REYMOND, R., intercartil-
aginous muscles, 414

mechanics of respiration, 439

respiratory movements, 466
DUCCHESCHI, blood osmotic pressure,
144, 145

blood plasma, 127

muscular tone, 319

sphygmography, 284
DUCHENXE, diaphragm, 410, 439

intercostal muscles, 411

scalene muscles, 410
DUCLAUX, anaerobic organisms, 69
DUKE, W. W., heart, 339
DUMAS, animals and plants, 55

blood, 94

DUNCAN, diffusion of gases, 379
DURANTE, thrombosis, 133
DUTROCHET, endosmometer, 141

v. EBNER, intercostal muscles, 412

intercostal spaces, 409
EBSTEIN, E., diastole, 231
ECKER, spleen, 549

ECKHARD, automaticity of heart, 305,
311

cardiac vagus, 324, 327

heart of invertebrates, 311

nervi erigentes, 350, 355, 367

neurogenic theory, 307, 337

vascular reflexes, 359

vasomotor centres, 365
EDELBERG, coagulation of blood, 138
EDGREN, cardiograms, 224, 231, 268

heart-sounds, 197

latent systole, 206

sphygmograph and sphygmograms,
267

velocity of pulse wave, 273
EDWARDS, W., respiration, 376, 400
EECKE (ver), thymus, 544
EGGERS, H. E., sinus venosus, 339

VOL. I

EGLI-SINCLAIR, periodic respiration.

493
EHRENBERG, infusoria and temperature

71
EHRLICH, anaerobic organisms, 69

examination of blood, 120

leucocytes, 114

red blood -corpuscles, 100
EICHHORST, cardiac vagus, 354
EINBRODT, mechanics of respiration and

circulation, 433
EINTHOVEX, intrathoracic pressure,.

427

ELLINGER, lymph formation, 526, 558
EMELIAXOW, splenectomy, 556, 558
EMMINGHAUS, lymph formation, 520
ENGEL, blood, 121

blood-platelets, 119

leucocytes, 114
ENGELMANN, active vasodilatation, 347

auriculo-ventricular bundle, 314

bacterium photometricum, 78

cardiac nerves, 325, 331

cardiogram, 290

chemotaxis, 74

compensatory pause, 321

electrical stimuli, 80

heart, suspension, 290

myogenic theory, 308, 314, 337

oxygen and ciliary movement, 68
ENGSTROM, foetal apnoea, 478
VAN ENSCHUT, blood gases, 377
ERASISTRATUS, arterial pulse, 264

circulation of blood, 159

diastole, 208

lacteals, 171

respiration, 370
ERB, marrow, 539
ERLANGER, J., auricular rhythm, 339

auriculo-ventricular bundle, 315

heart-block, 339

heart, conduction, 340
D'ERRICO, lymphagogues, 523

post-mortem lymph, 515
EULENBURG, vasomotor centres, 365
EULER, enzymes and catalysators, 32
EUSTACHIUS, lymphatic system, 171

valve of, 182
EWALD, experimental apnoea, 481, 504

intrathoracic pressure, 427
EYKMAN, molecular concentration, 148
EYSTER, J. A. E., extra-systole, 339

FABRICIUS, valves of veins, 165
FAIVRE, blood pressure, 253

heart beat, 225
FANO, active movements of lungs, 442

coagulation of blood, 134, 140

embryonic heart, 309

histogenic substances of plasma, 127

metabolism of heart, 332

myogenic theory, 308, 337

oscillations of auricular tonicity, 319'

2P

578

PHYSIOLOGY

FANO, osmotic pressure of blood,. 144, i
155

oxygen and heart, 293

peptone blood, 124

periodic respiration, 493, 497, ;">04

platelets, 118

sp. gr. of blood, 95

tissue respiration, 395

tonicity of heart, 319

vascular reflexes, 357
FANTINO, cardiac vagus, 333
FARKAS, reaction of blood, 94
FASOLA, active movements of lungs, 442
FEDERICO, urea and heart, 297
FERNET, gases of blood, 383, 385
FICK, A., diaphragm, 417, 439

diastole, 209, 213

expiration, 419

heart beat, 313

intercostal muscles, 412

intracardiac pressure, 201

manometer, 244

medical physics, 283

plethysmograph, 278, 281

pulse, 284

thoracograph, 415

work of heart, 230

FICK, R., respiratory muscles, 415, 439
FILEHNE, periodic respiration, 494, 498
FILHOS, active diastole, 213
FISCHER, E., enzymes, 31

phenyl-glucosazone, 37

poly-peptides, 28, 39

proteins, 26, 39
FITZGERALD, M. P., alveolar carbon i

dioxide, 439
FLACK, M., respiration and circulation, ,

439
FLEMMING, examination of blood, 120

lymph follicle, 529
FLETCHER, W. M., oxygen and muscle,

90, 401
FLOURENS, circulation, 162

noeud vital, 444

periodic respiration, 494, 503
FLUGGE, bactericidal properties of blood,

154
FOA, marrow, 539

megacaryocytes, 538, 557

platelets, 119, 121

spleen, 557
FODOR, bactericidal properties of blood,

154
FONTANA, extraction of gas, 377

gas of blood, 377

sleep, 502

FORMANEK, expired air, 397
FOSTER, M., active vasodilatation, 347

cardiac nerves, 328

circulation of blood, 163, 179

invertebrate heart, 311

lymphatic circulation, 517

phrenograph, 416

FOSTER, M., tissue respiration, 395
FOWLER, marrow, 539

spleen, 550, 556, 558
FRAOASSATI, respiration, 372, 400

thoracic duct, 171

FRANCHINI, inhibitory centres in bulb,
452

pulmonary vagus, 463
FRANCK, nitrifying bacteria, 58
FRANC.OIS-FRANCK, accelerators of heart,
330

cardiac plethysmograph, 289

cardiac reflexes, 336

cardiac vagus, 218, 326, 329, 335,
338

cardiograms, 223

centres of cardiac nerves, 336

heart, suspension, 291

pericardial fistula, 215

plethysmograph, 278

respiratory centres, 453

vascular reflexes, 357

vasomotor centres, 365
FRANK, R. T., conductivity of blood,

156

FRANKEL, gas of blood, 384, 400, 474
FRANZEL, periodic respiration, 502
FRASSINETO, DI, plasma, 127
FREDEUICQ, aero tonometer, 388

apnoea vera, 476, 504

circulation of blood, 281

experimental apnoea, 476, 490

gases of blood, 386, 390

heart beat, 231

intracardiac pressure, 203, 210

latent systole, 210

oesophageal sphygmograms, 229

spleen, 553

stimulation of pulmonary vagus, 462

systolic aspiration, 203, '210

venous pulse, 203
FRERICHS, urea in selachii, 297
FREUND, animal gum, 130

thrombosis, 133
v. FREY, diastole, 209

haematoidin, 108

intracardiac pressure, 201

tonograph, 245

vasomotor nerves, 351
FRIEDLEBEN, thymus, 542
FRIEDREICH, auriculo- ventricular valves,

192

FROMMAN, structure of protoplasm, 17
FRY, H. J. B., heart, cephalopod, 340
FUNKE, haemoglobin, 107

leucocytes, 175

mechanics of respiration and circula-
tion, 434

spleen, 549
FUSARI, nerves in spleen, 549

GABRITSCHEWSKI, pinocytosis, 534
GAD, circulation of blood, 281

INDEX OF AUTHOKS

579

GAD, elimination of C02, 470

experimental apnoea, 477

manometer, 245

platelets, 119

pulmonary vagus, 458, 462

residual air, 423

respiratory centre, 446, 504

respiratory rhythm, blood, 479, 486

tachypnoea, 471

GAGLIO, lactic acid of blood, 131
GALEN, active diastole, 208, 213

arterial pulse, 264

automatism of heart, 299

circulation of blood, 159, 171

"de usu partium," 4, 9, 400

intercostal muscles, 411

mechanics of respiration, 403

pulmonary vagus, 457

respiration, 370

respiratory centres, 444

semilunar valves, 187

spleen, 555

systole and diastole, 180, 208
GALEOTTI, electrical conductivity of
serum, 150

electrical conductivity of tissues, 155
GAMGEE, blood, 121

oxyhaemoglobin in magnetic field, 121
GARDELLA, coagulation, 124, 155
GARELLI, molecular weights, 155
GARTNER, molecular concentration of
blood, 148

tonometer, 252
GASKELL, accelerator nerves, 328

active vasodilatation, 347, 367

auriculo-ventricular bundle, 314, 316,
321

automatism of heart, 306, 338

cardiac plethysmograph, 289

cardiac vagus, 324, 338

heart, electrical variations, 332

neart, suspension, 289

myogenic theory, 307, 314

nervi erigentes, 355, 367
GASSENTI, circulation, 166
GASSER, ganglion of, 328, 354
GAULE, diastole, 208

diastolic aspiration, 212

intracardiac pressure, 207, 212, 214,
220

normal physiological solution, 295

pressure of blood, 254
GAUTIER, anaerobic organisms, 69
GEGENBAUER, lymphatic vessels, 508
GEPPERT, blood gas, 284, 400, 474

muscular work, 470

respiration 504

GERLACH, bronchial muscle, 442
GIANNUZZI, cardiac vagus, 332
GIBBES, haemolymphatic glands, 557
GIBSON, periodic respiration, 492, 504
GIERKE, respiratory centre, 446, 504
GIES, artificial respiration, 504

G-IES, osteomucoid, 40,

protagon, 40

GIRARD, respiratory centre, 446
GLEY, cardiac sound, 200

extra-systole, 321

lymphatic vessels, 517, 557
GMELIN, blood gas, 377
GOLDSTEIN, tachypnoea, 471
GOLGI, haemorrhage, 152
GOLTZ, automatism of heart, 305, 337

blood pressure, 254

cardiac vagus, 336

diastole, 209

hyperaemia, paralytic, 345

intracardiac pressure, 208, 214

reflex inhibition of heart, 336

vaso-dilatators, 350, 367

vasomotor centres, 362, 364, 366
GOOD ALL, spleen, 551

thymus, 558
GOTHLIN, normal physiological solution,

296, 338
GRAHAM, colloids and crystalloids, 21

diffusion of gases, 379
GRAM, solution of, 103
GRANCHER, leucocytes, 116
GRANDIS, elimination of C02, 391
GRASHEY, dicrotic wave, 284
GRASSI, mosquitoes and coagulation, 124
GRAUPNER, auriculo-ventricular bundle,

315

GRAWITZ, blood, 121
GREER, J. R., lymph formation, 52*5,
559

salivary glands, 558
GREHANT, residual air, 423
GRIFFINI, spleen, 557
GRISELINI, circulation, 166
GROSS, normal phvsiological solution,

297

GRUBER, cell, rhizopoda, 13
GRUNMACH, cardiograph, 223

latent systole, 206

velocity of blood stream, 273
GRUTZNER, vascular reflexes, 360, 367

vaso-constrictors, 349

vaso-dilatators, 351
GRYNS, serum, osmotic pressure, 144
GSCHEIDLEN, quantity of blood, 99
GUERICKE, air pump, 371
GULLAND, spleen, 551, 556, 558
GUNTHER, circulation of blood, 162
GURBER, plasma, mineral matter, 132

respiratory gases, 389
GURBOKI, cardiac vagus, 335
GURWITSCH, spleen, 552, 558
GUTHRIE, C. C., blood pressure, 284

blood pressure and respiration, 439

coronary pressure, 339

red blood-corpuscles, 122

HADLEY, P. B., galvauotaxis, 90
HAECKEL, the cell, 13

580

PHYSIOLOGY

HAECKEL, protista, 56
HAESER, vital capacity, 423
HAFIZ, vaso-constrictors, 349
HALDANE, J. S., alveolar C02, 439
barometric pressure and respiration,

439

blood gases, 391, 400, 401
Gheyne-Stokes breathing, 504
haemo-globinometry, 121
regulation of respiration, 439, 504
HALES, blood pressure, 241
" pneumatic " chemistry, 373
velocity of blood in capillaries, 263
HALLEU, activity of heart, 299
auriculo-ventricular valves, 192
circulation of blood, 160, 164, 167,

172, 341
diastole, 208

"elementa physiologiae," 9
intercostal muscles, 410
mechanics of respiration, 403
respiration, 429, 439
HAM, E., blood, 122
HAMBERGER, intercostal muscles, 410,

412, 439

semilunar valves, 187
HAMBURGER, blood gases, 386
lymph formation, 526, 584
molecular concentration, 142, 147
osmotic pressure and ions, 121, 155
osmotic pressure of plasma, 143
osmotic pressure of serum, 144
semilunar valves, 187
HAMMARSTEN, coagulation of blood, 135
enzymes, 32
lymph gases, 514
nucleoproteins, thymus, 545
physiological chemistry, 39
proteins of plasma, 128
salted plasma, 128
HAMMEKSCHLAG, sp. gr. of blood, 95
HANRIOT, lipase of blood, 127
HARDY, colloidal solution, 40

leucocytes, 113
HARRIS, T. F. , proteins, 40
HARRISON, haemolymphatic glands, 557
HARTLEY, P., fat of liver, 41
HARTWELL, intercostal muscles, 412,

414, 439

HARVEY, afferent nerves of heart, 335
circulation, 166, 169, 171
diastole, 208
heart beat, 222, 225
heart sounds, 196
rate of blood stream, 259
respiration, 371
systole, 182

HARWOOD, W. S., botany, 63
HASLAM, H. C., proteins, 40
HASSE, diaphragm, 410
HASSELBACH, blood gases, 395
HAWK, P. B., blood and muscular work,
122

HAYCRAFT, blood, anti-coagulants, 124

systole, 186

HAYEM, coagulation of blood, 134
haemacytometry, 103
haematoblasts, 100, 118, 121
haemorrhage, 152

HEDBLOM, C. A., blood pressure, 284
HEDIN, centrifuge, 98
enzymes in blood, 156
haematocrite, 104, 121
molecular concentration, 147
HEDON, isolation of heart, 291
HEFFTER, oxygen and activity of heart,

293
HEGER, P., diapedesis, 179

vascular reflexes, 355
HEIDENHAIN, accelerators of heart, 328
cardiac vagus, 218, 324, 325, 329
formation of lymph, 519, 557
lymphagogues, 523
megacaryocytes, 535
periodic respiration, 494
quantity of lymph, 514
respiratory centre, 445
Stannius heart, 300
vascular reflexes, 360, 361
vaso-constrictors, 349
vaso-dilatators, 351
vasomotor centres, 363
HEIN, periodic respiration, 502
HEINRICIUS, mechanics of circulation

and respiration, 435, 439
HEITZMANN, structure of protoplasm,

17

HELLER, contraction of lymphatics, 517
HELLRIEGEL, nitrifying bacteria, 58
HELMHOLTZ, conservation of energy, 5

resonators, 197
VAN HELMONT, intercostal muscles, 411

respiration, 371, 373, 400
HENDERSON, J., thymus, 558
HENDERSON, Y., heart volume, 231
HENLE, blood-vessels, active move-
ments of, 341
cardiac vagus, 323
intercostal muscles, 412
myocardium, 182
HENEIQUES, vagi and gas exchange,

392

HENRY, gas law, 378, 384
HENSEN, plankton, 82
HERBST, quantity of blood, 98
HERICOURT, toxicity of blood, 153
HERINO, Ed., circulation time, 282
BERING, Ew., automatic control of

respiratory rhythm, 459, 503
blood and respiratory rhythm, 480, 486
cardiac vagus, 336
diapedesis, 177
experimental apnoea, 486
inspiratory centres, 456
living matter, metabolism, 86, 89
oscillations of vascular tone, 500

INDEX OF AUTHOES

581

HERING, Ew., trigemiims and respira-
tion, 464

Traube-Hering waves, 343
HERING, H. E., auriculo-ventricular

bundle, 315, 317, 337
cardiac nerves, 310
cardiac vagus, 327
isolated heart, 291
resuscitation of heart, 298
HERING. P., blood and respiratory

rhythm, 480, 486

HERMANN, demarcation and action
' currents, 332
galvanotaxis, 81
gases of expired air, 397
lungs of newborn, 405, 439
oxygen and muscle (frog), 68
physiology, handbook, -9
tissue respiration, 394
HEROPHILUS, arterial pulse, 264
lacteals, 171
respiration, 370

HERTWIG, 0., cell and tissues, 39
HERTWIG, R., amoeba, 13

centersome, 13
HERZEN, spleen, 553
HESSE, myocardium, 182, 190
HEWSON, coagulation, 132, 135
leucocytes, 93
respiration, 373
HIFFELSHEIM, heart-beat, 225
HILL, L., blood in high barometric

pressure, 401

residual arterial pressure, 284
respiration and circulation, 439
HIRSCHFELD, platelets, 119
HIRSCHFELDER, A. D., extra - systole,

339

HIRT, spleen, 552
His, W., lymphatic system, 179
His, jun. , auriculo-ventricular bundle,

315

embryonic heart, 308
HOBER, physical chemistry, 121
VON HOESSLIN, spirometry, 423
HOFER, amoeba, 14
HOFF, VAN T', solutions, 141
HOFFA, delirium cordis, 321
HOFFMANN, K., circulation of blood,

170
HOFMANN, auriculo-ventricular bundle,

317, 337
HOFMEISTER, enzymes, 29

proteins, 25
HOLMGREN, blood gases, 380

circulation in capillaries, 173, 178
HOLT, E. B., phototaxis, 90
HOOK, experimental apnoea, 476

respiration, 371, 400
HOOKER, heart, 339

post-mortem lymph, 515, 558
HOORWEG, dicrotic wave, 269
HOPKINS, F. G., ammo-acids, 40

HOPKINS, F. G., proteins, 40
HOPPE-SEYLEU, blood gas, 377, 380,
400

diffusion of gas, 379

haemoglobin, 105

lecithin. 35

leucocytes, 117

oxyhaemoglobin, 383

physiological chemistry, 39

plasma and corpuscles, 125

plasma soaps, 130

proteins, 24

stromata, 106

tissue respiration, 393
HORBACZEWSKI, spleen, 552
HORNE, coagulation, 137
HOWELL, W. H., heart, 338, 339

heart inhibition, 339

megacaryocytes, 535, 584

proteins of blood, 156

vagus action, 339
HUFNER, haemoglobin. 107

oxygen of blood, 383, 420

spectro- photometry, 111
HUGHES, W. T., haemolytic lymph, 559
HULTKRANTZ, respiration, 418
HUMBLET, auriculo-ventricular bundle

315, 337

v. HUMBOLDT, oxygen and heart, 293
HUNT, REID, cardiac nerves, 331
HUNTER, blood, 94

invertebrate heart, 311
HUNTER, W., cerebral vascular nerves

368
HURTHLE, cardiograph. 222

dicrotic wave, 269

haemodromometer, 259, 284

intracardiac pressure, 201

latent systole, 206

manometer, 244

sphygmomanometer, 250

viscosity of blood, 151
HURTLEY, W. H., sulph-haemoglobin,

122
HUTCHINSON, intercostal muscles, 412,

439

spirometry, 422, 439
types of respiration, 416, 439
HYDE, heart, automatic control, 211

respiratory centre, 504
HYRTL, semilunar valves, 187

INGENHOUSZ, plant metabolism, 54

JACKSON, H. C., splenectomy, 558
JACOBSON, hydrodynamics, 235

intrathoracic pressure, 427

plasma, jecorin, 130

venous pressure, 253
JACQUET, tissue respiration, 393, 400
DE JAGER, diastole, 209, 214

intracardiac pressure, 207, 214
JAKOWICKI, coagulation of blood, 138

582

PHYSIOLOGY

v. JAKSCH, reaction of blood, 96
JAPPELLI, tistula of, 513

polypnoea, 471

post-mortem lymph, 515
JENSEN, cblpidinm colpoda and inani-
tion, 66

geotaxis, 77
JOHANSSOHN, cardiac vagus, 218, 326

vasomotor centres, 366
JOLYET, rate of blood stream, 238
JONES, WHARTON, vascular rhythm, 343

KABIEIISKI, vasomotor centres, 364
KAISER, extrasystole, 321

heart stimuli, 321
KANTHAOK, leucocytes, 113
KATZBNSTEIN, respiratory movements,

466

KAUFMANN, periodic respiration, 502
KAYA, R., phospho- proteins, 41
KAZEM-BECK, depressor, 334
KEITH, heart beat, 224
KELLER, hydrostatic pressure, 72
KEMP, G. T., blood-platelets, 121
KENDALL, vasodilatators, 351
KENT, STANLEY, auriculo - ventricular

bundle, 314
KEYT, latent systole, 206

velocity of blood .stream, 273
KING, W. 0. K., blood, 401
KITASATO, immunisation, 154
KIWISCH, heart beat, 225
KLEEN, vascular reflexes, 360
KLEIN, lymphatics, 509, 530
KLEINBNBERG, examination of blood,

120

KLIKOWICZ, formation of lymph, 525
KLUG, automatic control of heart, 211

cardiac vagus, 333

oxygen and heart, 293
KNIGHT, geotaxis, 77
KNOLL, cardiograph, 223

experimental apnoea, 476

heart, suspension, 291

pneumoplethysmograph, 425, 491

vascular reflexes, 360
KOCH, anthrax bacilli, 71
KOCHER, splenectomy, 555
' KOCHS, potential life, 67
EOHLUAUSCH, electrical conductivity,

149

V.^KOLLIKER, spleen, 546, 549, 552
KONIG, tuning-fork, 6
KONOW, cardiac vagus, 333

depressor, 335

vasomotor centres, 364
KOPPE, molecular concentration of blood,
147, 155

platelets, 119

KORSCHINSKI, heterogenesis, 52
KOSSTCL, histones, 106, 117

nucleus, 39

proteins, 25

KOSSEL, proteins of cell, 39

structure of proteins, 25
KOSTEK, depressor, 335
KOWALEWSKI, vasomotor centres, 365 {
KRATSCHMER, trigeminus ^and respira-'

tion, 464
KREHL, auriculo-ventricular valves, 194

diastole, 212, 215, 231

diastolic aspiration, 209

myocardium, 182, -184

myogenic theory, 314
VON KRIES, capillary pressure, 253

circulation time, 283

pulse, 284
KROGH, blood gases, 395

nervous system and gas exchange,

392, 420

KRONECKER, cannula (perfusion), 288,
337

co-ordination of heart, 321, 337

heart muscle, 318, 321

mechanics of respiration and circula-
tion, 435, 439

normal physiological solution, 295

periodic respiration, 495, 502

red blood-corpuscles, 105

respiratory centres, 448

transfusion of blood, 153
KutJGER, spleen, 551
KRUSS, spectrophotometer, 112
KUHNE, chemical stimuli, 73

electrical stimuli, 80

reaction of blood, 95

thermal tetanus, 77
KULIABKO, heart, resuscitation, 298
KUKLOW, splenectomy, 555
KURSCHNEK, activity of heart, 231

auriculo-ventricular .valves, 192

neurogenic theory, 307

presystole, 181

Kiiss, auriculo-ventricular valves, 192
KUSSMAUL, asphyxia, 479

LABORDE, cardiac centres, 336
LAENNEC, heart sounds, 196

mechanics of respiration, 403
LAFFONT, vasomotor centres, 366
LAGRANGE, respiration, 375
LAIDLAW, P. P., blood pigments, 122
LAMARCK, biology, 1

evolution, 48, 65
LAMBERT, urea and heart, 297
LANCISI, automatic control of heart, 211
LANDERGREEN, asphyxia, 452
LANDOIS, autosphygmogram, 265, 283

cardio-pneumatic curves, 227

intercostal muscles, 412

latent systole, 206

lungs, movements, 426

mechanics of respiration and circula-
tion, 437

pulse, 231

reaction of blood, 96

INDEX OF AUTHOKS

583

LANDOIS, toxicity of serum, 153

transfusion of blood, 153

vasomotor centres, 365
LANGENDORFF, asphyxia and heart, 304

ciliary ganglion, 310

heart, isolation, 291, 338

normal physiological solution, 297

oxygen and heart, 293, 338

periodic respiration, 493, 501, 504

respiratory centres, 447, 451

stimulation of heart, 321
LANGERHANS, thymus, 542
LANGLEY, vaso-dilatators, 354
LAPICQUE, spleen, 551
LAPLACE, respiration, 400
LASSAR, reaction of blood, 96
LATSCHEMBERGER, mechanics of respira-
tion and circulation, 434

vasomotor centres, 363
LAUDENBACH, lymphoid organs, 558
LAVOISIER, animal respiration, 54, 374,
400

chemistry of respiration, 396

indestructibility of matter, 5

modern chemistry, 396

volume of expired air, 398
LAZARUS-BARLOW, formation of lymph,

526

LEAVENWORTH, proteins, 40
LEBER, chemotaxis, leucocytes, 178
LEE, F. S., phototaxis, 90
LEEUWENHOEK, anabiosis, 66

capillary circulation, 172

red blood-corpuscles, 93
LEFEVRE, systolic aspiration, 210
LEGALLOIS, pulmonary vagus, 157

respiratory centre, 444
LEGROS, cardiac vagus, 324
LEHMANN, blood, 94

quantity of blood, 98
LEPINE, glycolysis in blood, 127

vasomotors, 352

LEROYENNE, rate of blood stream, 275
LESEM, W. W., protagon, 40
LESSER, transfusion of blood, 153
LEUBE, periodic respiration, 502
LEVENE, P. A., autolysis, 40

edestin, 40

proteose, 40
LEWANDOW.SKY, nervous mechanism of

respiration, 504
LEWIS, T., heart rhythm, 231

sphygmograni, 284

thoracic movements and blood -

pressure, 284

LEYDIG, haemolymphatic glands, 557
LIEBERKUHN, glands of, 528

leucocytes, 115
LIEBIG, animals and plants, 55

oxygen of blood, 383
LIEBREICH, protagon, 35

reaction of blood, 95
LILIENFELD, coagulation of blood, 136

LILIENFELD, lymphocytes, 117

molybdate test, 39

platelets, 118

LILLIE, R. S., electrical convection, 90
v. LIMBECK, lyinphagogues, 525

osmotic pressure of blood, 146

pathology of blood, 155
LINDHAGEN, pulmonary vagus, 459
j LINGLE, D. J., heart rhythm, 231

ions and heart, 338
LINNAEUS, animals and plants, 53

immutability of species, 45
LITTEN, marrow, 539

spleen, 556

I Lo BIANCO, marine biology, 90
| LOCK, R. H., variation, 63
I LOCKE, F. S., glucose and heart, 296,
338, 339

normal physiological solution, 296, 338
' LOEB, cell theory, 12

galvanotaxis, 80

general physiology, 90

geotaxis, 77

heliotaxis, 79
I LOEWY, acapnia, 475, 504

pulmonary gas exchange, 392, 400

respiratory centres, 464

trigeminus and respiration, 465

water of alveolar air, 391
LOMBARD, W. P., heart rhythm, 231
Lo MONACO, thymus, 542, 558
LONGET, bronchial muscle, 442

intercostal muscles, 411

respiratory centre, 444

" Traite de physiologic," 9
LORRY, respiratory centre, 444
LORTET, sphygmograms and tachy-

grams, 276

LOTSY, doctrine of descent, 62
LOVEN, cervical plexus, 349

negative pulse, 227

vascular reflex, 356, 359, 367
LOWER, auriculo - ventricular valves,
192, 400

respiration, 372, 400
LOWIT, platelets, 118
LUBARSCH, chemotaxis, leucocytes, 178
LUCHSINGER, periodic respiration, 495,
501, 504

vaso-dilatators, 351
LUCIANI, active vaso-dilatation, 347

active diastole, 208, 214, 231

activity of heart, 300, 337

auriculo- ventricular valves, 194

automaticity, 85

automaticity of heart, 215

automatism of respiratory rhythm,

,. 498, 504

cardiac vagus, 217

excitability and sensibility, 45

experimental apnoea, 480, 484

expiration, 419

haemodromometer, 258

584

PHYSIOLOGY

LUGIANI, human bulb, 445

inanition, 65

inspiratory centres, 456

intra-abdominal pressure, 429

intrathoracic pressure, 407

intrathoracic and intra - abdominal
pressures, 231, 427

leucocytes, 116

mechanics of respiration and circula-
tion, 430, 439

minimal life, 67

oesophageal sound, 228, 429

oesophageal sphygmograms, 228

oxygen and heart, 293

periodic respiration, 494, 501

periodic rhythm of heart, 302

plethysmograms and tachygrams, 280

pulmonary vagus, 458

rectal explorer, 429

red blood-corpuscles, 105

respiratory movements in asphyxia,
425, 448

ribs, 408

section of phrenics, 435

semilunar valves, 189

staircase phenomenon, 318

tonographic apparatus, 288

transfusion of blood, 153
LUCKHARDT, A. B., lymph formation,

526, 559

LUDWIG, accelerated cardiac rhythm,
181

accelerators of heart, 327, 338

auriculo- ventricular valves, 192

blood pressure, 241, 254

cardiac ganglia, 299

cardiac systole, 182, 187

delirium cordis, 321

depressor, 333, 360, 367

formation of lymph, 519

gases of blood, 367, 377, 379

glandular secretion, 391

haemodromometer, 257

heart beat, 224

heart sounds. 197

hydrodynamics, 189

kymograph, 242

lymphatic circulation, 518, 522
, lymphatic pressure, 516, 557

mechanics of respiration, 439

myocardium, 182

normal physiological solution, 295

physiology, text-book, 231

pulmonary catheter, 388

recording manometer, 207

serous cavities, 509

splanchnic nerve, 347

vasomotor centres, 347, 362, 366
LUNIN, assimilation of inorganic matter,

62

LURIA, respiratory reflex, 466
LTJSCHKA, thorax, 409
LUSSKY, H. 0., lymph, 559

LYON, excitation, 90

geotropism, 90

rheotropism, 90
LYONET, apparatus of, 173

MAAR, nerves and gas exchange, 392
McCoLLUM, nuclein synthesis, 41
M'CuRDY, F. H., blood pressure, 284
MACH, sensations, 6
MACKENZIE, venous pulse, 203
MACLEOD, J. J. R., blood at high

pressures, 401

MACNALTY, S., heart rhythm, 231
MACWILLIAM, automatism of heart, 306

cardiac vagus, 326

chloroform, heart, 338

delirium cordis, 321

rigor mortis, heart, 231
MAFFUCCI, spleen and liver, 556
MAGENDIE, auriculo-ventricular valves,
196

cardiac diastole, 213

circulation, 341

haemodiastase, 134

heart sounds, 196

intercostal muscles, 411

vascular reflexes, 359
MAGGIOHANI, spleen and liver, 556
MAGNUS, G., blood gases, 377, 400
MAGNUS, R., oxygen and heart, 294

vagus, 553
MAISSIAT, intercostal muscles, 411, 439

thoracic respiration, 417
MALASSEZ, haemacytometer, 102, 116

isotonic solution, 143
MALERBA, cardiac vagus, 323
MALFATTI, nucleus, 39
MALPIGHI, capillary circulation, 172

corpuscles, spleen, 547

fibrin, 97

red blood-corpuscles, 93

structure of lungs, 403
MANCA, osmotic pressure of blood, 146,

155

MANTEGAZZA, coagulation, 134
MARAGLIANO, vascular reflexes, 357
MARCACCI, ANT., intercostal muscles,

414, 439
MARCACCI, ART., extrasystole, 321

tissue lymph, 527
MARCHAND, respiration, 376
MARCKWALD, blood and respiratory
rhythm, 494

periodic respiration, 496, 502, 504

respiratory centres, 448, 464

trigeminus and respiration, 465
MAREY, arterial pressure, 241, 248, 433

cardiac myograph, 291, 337

cardiograph, 223

cardiographic sound, 200

circulation of blood, 231, 284

diaphragm, 433

heart beat, 224, 225

INDEX OF AUTHOKS

585

MAREY, intracardiac pressure, 201

latent systole, 206

metallic manometer, 244

refractory period, 320, 337

pneumograpli, 415

recording tympanum, 201

sphygmograph, 264, 284

sphygmomanometer, 247

sphygmoscope, 205

vascular walls, 241

waves, 241

MARIANNINI, heart beat, 222
MARIETTE, anabiosis, 66
MARIOTTE, gas law, 378
MARINESCO, respiratory centre, 446,

504
MARKS, H. K. , vasomotor centres, 368

vasomotor reflexes, 368
MARSHALL, A. K., bionomics, 63
MARTIGNI, COLLARD DE, respiration,

377
MARTIN, cerebrum and respiration, 453

intercostal muscles, 412, 414, 439

isolation of heart, 291

heart, oxygen, 401

MARTIN, E. G., heart, potassium, 338
MARTIUS, normal physiological solution,
295

oesophageal pulsations, 230
MASCAGNI, formation of lymph, 519

serous cavities, 509
MASIUS, vascular reflexes, 357

vasomotor centres, 366
MASOIN, cardiac vagus, 324

intercartilaginous muscles, 415
MASSART, chemotaxis, leucocytes, 75,
178

phagocytosis, 116

MATTHEWS, S. A., blood pressure, 284
MATJROCORDATO, circulation, 160
MAYER, viscosity of blood, 151
MAYER, J. R., conservation of energy, 5

metabolism of green plants, 55
MAYOW, intercostal muscles, 411

respiration, 372, 377, 400
MECKEL, auriculo - ventricular valves,

192

MEEK, W. J., heart, 339, 340
MEISSNER, intercostal muscles, 412
MELLANBY, J., coagulation", 156

serum, 156

MELTZER, C., vasomotor nerves, 368
MELTZER, S. J., artificial respiration,
504

cardiac nerves, 331

vasomotor, 368
MENDEL, L. B., edestin, 40

lymph, 558

splenectomy, 558
MENDEL, evolution, 52

post-mortem lymph, 515
MENDELEJEFF, periodic system, 20
MENDELSSOHN, thermotaxis, 78

MERKEL, periodic respiration, 502
MERRIMAN, C. IL, mutation, 63
MERUNOWICS, normal physiological

solution, 295
METSCHNIKOFF, chemotaxis, 75

inflammation, 179

phagocytosis, 18, 115
MEYER, blood gas, 380, 383

cardiac vagus, 324

experimental apnoea, 479

respiration, 377, 400
MICANZIO, circulation, 166
MICHAELIS, fats, blood, 127
MIESCHER, apnoea, true and false, 477,
488, 504

leucocytes, 117

nucleo-proteins, 24, 39

plasma, histogenic substances, 126
MILLER, J. R., galvanotropism, 90
MILLON, protein reaction, 22
MILLS, WESLEY, cardiac vagus, 324,

326

MILNE-EDWARDS, comparative physi-
ology, 9

division of labour, 91

lymphatic system, 509
MINCK, diastolic aspiration, 212
MIRTO, depressor nerve, 335
MISLAWSKI, respiratory reflex, 466

vasomotor centres, 366
MOENS, velocity of pulse wave, 273, 284

waves, 241

MOHL, protoplasm, 11
MOLESCHOTT, cardiac vagus, 322

tissue respiration, 394
MOLISCH, proteins reaction, 22
MONTENOVESI, spleen and liver, 556
MONTI, test for phosphorus, 39
MOORE, sugar reaction, 36
MOORE, A., geotropism, 90

lymph hearts, 558
MOORE, B., spleen, 554, 558
MORAT, cardiac vagus, 323

cervical sympathetic, 349, 353, 367

nerves of neck (rabbit), 334

vascular reflexes, 361, 367

vasomotor centres, 366

vasomotor nerves, 351, 353
MORAWITZ, coagulation, 156

thrombokinase, 139
MORGAGNI, spleen, 555
MORGAN, Th. H., evolution, 63
MORNER, ovo-nmcoid, 126, 129
Mosso, A., acapnia, 474

asphyxial pause, 452

blood pressure, 253, 284

cardio-pneumograms, 227, 231

diastolic aspiration, 210

inspiratory centres, 456

periodic respiration, 493

plethysmograph and plcthysmograms,
279, 344, 367

pulse, 231, 284

586

PHYSIOLOGY

Mosso, A., respiration at high altitudes,

472, 499
luxus respiration, 472

sphygmomanometer, 284
thoracic and abdo

thoracic and abdominal respiration,
418, 439

tidal air, 423

tonicity of respiratory muscles, 504

toxicity of heterogeneous blood, 153

vascular tone, 346

voluntary apnoea, 480, 483
Mosso, U., periodic respiration, 494

respiration at high altitudes, 474
MULDER, blood, 94
MULLER, F., acapnia, 475

respiration at high altitudes, 504

splenic cells, 549
MULLER, J., blood gases, 376

cardiac ganglia, 299

coagulation, 135

life, 3, 9

mechanics of respiration and circula-
tion, 436

physiology, .3, 9

respiration, 376

solution of, 104
MULLER, W., oxygen of blood, 384

respiratory valves, 420
MUNK, I., lymph, 514

urea of blood, 129

MURE, DE LA, locomotion of blood-
vessels, 277

MURRAY, marine biology, 81
MURRI, periodic respiration, 502
MYERS, W., erythrocytes, 121

NAGEL, W., physiology, handbook, 9
NAGELI, adaptation, 65

evolution, 49, 62
NAMIAS, heart beat, 222
NASINI, solutions, 155
NASSE, blood, 94

extraction of gas, 377

glycolysis in blood, 127
NEANDER, apnoeic respiratory pause,

482, 504

NEGA, systolic aspiration, 210
NEGRI, red blood-corpuscles, 540
NEILSON, C. H., enzyme action, 40
'fats, 40

inversion of starch, 40
NEUMANN, marrow, 534, 557

spleen, 550
NEUMEISTER, physiological chemistry,

39

NEWMAN, H. H., heart, 401
NICOLAIDES, rate of circulation, 260
NOBBE, nitrifying bacteria, 58
NOLF, coagulation, 140
NOLL, lymphatic pressure, 516
NOLL, F., botany, 62

heliotaxis, 79

nitrifying bacteria, 58

NOTE NAGEL, lympathic vessels, 512
NOWAK, expired air, 397
NUEL, cardiac vagus, 326
NUTTALL, bactericidal properties of
blood, 154

OEHL, abdominal vagi, 348

cardiac valves, 183, 191

diastolic aspiration, 212

luminous stimuli, 78
OEHRWALL, oxygen and heart, 293, 338

tonographic apparatus, 288
ONIMUS, cardiac vagus, 324
OPPEL, spleen, 548
OPPENHEIMER, ferments, 40
ORIBASUS, pneumothorax, 403
ORTH, marrow, 539

spleen, 556

OSBORNE, T. B., proteins, 40, 41
OSBORNE, W. A., oxygen tension of

blood, 401

OSLER, platelets, 118
OSTROUMOFF, tissue lymph, 527

vasomotor nerves, 351, 354
OSTWALD, catalysis, 31

energetic monism, 6

viscosimeter, 151
OTTO, glucose of blood, 130
OUSKOFF, leucocytes, 114
OWSJANNIKOW, vasomotor centres, 363

PACINI, mechanics of respiration and
circulation, 436

solution of, 103
PACKARD, A. S., evolution, 63
PAGLIANI, diastolic aspiration, 210

neurogenic theory, 308
PALADINO, auriculo-ventricular bundle,
314

auriculo-ventricular valves, 191, 231

erythroblasts, 539
PANUM, cardiac vagus, 332

transfusion of blood, 153
PAPPENHEIM, platelets, 119
PARCHAPPE, active diastole, 213

auriculo-ventricular valves, 192
PASCHUTIN, formation of lymph, 522
PASTEUR, aerobic and anaerobic organ-
isms, 69, 369

ferments, 30
PATON, N., lymph, 514, 557

spleen, 550, 556, 558

thymus, 558
PATRIZI, bulb, inhibitory centres, 452

periodic respiration, 493

pulmonary vagus, 463

rate of pulse wave, 273, 284

vascular reflexes, 358, 367
PAULY, Darwinism and Lamarckisin, 62
PAVY, glycogen of blood, 131
PAWLOW, cardiac nerves, 338

quantity and pressure of blood, 255
PEARL, R., galvanotaxis, 90

INDEX OF AUTHOKS

587

PEARSON, K., evolution, 62, 63
PECQUET, lymphatic system, 171, 505
PEKELHARING, coagulation, 139
PELLACANI, marrow, 539
PESKIND, S., blood-corpuscles, 121, 122
PETRONE, coagulation, 134

erythrocytes, 540, 558
PETTENKOFER, nitrogen of blood. 387
PEYER, patches of, 530
PFEFFER, chemotaxis, 75, 178

osmotic pressure, 141

vegetable physiology, 62
PFEIFFER, fats of blood, 130
PFLUGER, animals and plants, 89

apnoea, 476, 477

blood gases, 377, 379, 387

blood and respiratory rhythm, 479,
486

cardiac vagus, 324

embryonic heart, 308

eupnoea, 472

living matter, 86, 89

oxygen and life, 70

pulmonary catheter, 388

splanchnic and respiration, 465, 504

tissue respiration, 86
PICTET, R., cold and life, 71
PIEGEAUX, heart beat, 222
PIEGU, plethysmograph, 278
PIKE, F. H., blood pressure, 439

heart, 339

resuscitation of bulb, 504
PILCHER, J. D., vasomotor centre, 368
PILLSBURY, heart rhythm, 231
PIOTROWSKI, vasomotors, 353, 367
PIUTTI, minimal life, 67
PLIMMER, R. H. A., caseinogen, 40

phosphoproteins, 24, 41
PLINY, splenectomy, 555
PLOSZ, nucleoproteins, 24

strom ata, 106
POISEUILLE, blood pressure, 241

circulation, 174, 341

mechanics of thoracic movements, 430

plethysmograph, 278
PONFIK, transfusion of blood, 153
PORTAL, thoracic duct, 171
PORTER, automatic control of heart, 211

automatism of heart, 306

heart, tonus, 339

intracardiac pressure, 206

myogenic theory, 313

oxygen and heart, 293

vasomotor centre, 367, 368
POSNER, E. R., protagon, 40

proteins, 40

POTAIN, blood pressure, 246
POUCHET, spleen, 556
POULTON, E. B., bionomics, 63
POTJLTON, E. P., respiration, 439
PRAXAGORAS, circulation, 162
PREVOST, blood, 94

terminal respiration, 452

PREYER, anabiosis, 66

blood gases, 387

circulation of blood, 160

haemin, 108, 121
PRIESTLEY, modern chemistry, 94

respiration, 373, 377, 400
PRIESTLEY, J. G., respiration, 504
PRZEWOSKI, myocardium, 313
PUGLIESE, formation of lymph, 527

lymphagogues. 523
PUNNETT, K. C., merism and sex, 63
PURKINJE, myocardium, 313

systolic aspiration, 210
PUSATERI, depressor, 335

QUETELET, law of, 48

RABINOWITZ, blood pressure, 246
RANSOM, heart, invertebrates, 311
RANVIER, coagulation, 134

lymphatic vessels, 505, 557

myogenic theory, .'!07

serous cavities, 509
RAOULT, molecular concentration. 142

solutions, 141
REBATEL, automatic control of heart,

211
VON RECKLINGHAUSEN, diapedesis, 175

serous cavities, 509
REGNARD, blood gases, 387
REGNAULT, expired air, 387, 417
REGOLI, calcium and coagulation, 137
REICHERT, E. T., haemoglobin crystals,

122

REID, E. W., haemoglobin, 122
REID, myocardium, 183
REISET, expired air, 387, 417
REMAK, cardiac ganglia, 299

protoplasm, 17
RESTELLI, thymus, 542
RETTGER, L. J., coagulation of blood,

156

RETXIUS, nerves in spleen, 549
RICHARDS, A. N., elastic tissue, 40
RICHARDSON, R., vasomotor reflexes, 368
RICHET, circulation, 165

polypnoea, 471

toxicity of blood, 153

vasomotor centres, 365
RIDDLE, 0., blood pressure, 284
RIEGEL, vascular rhythm, 343
RIGNANO, evolution, 62
RINDFLEISCH, erythroblasts, 539
RINGER, normal physiological solution,

296
RIOLAN, circulation, 170

perisystole, 180
RiVA-Rocci, blood pressure, 253

sphygmomanometer, 251, 284
RIVE, latent systole, 206
ROAF, H. E., haemoglobin, 156
ROBERTS, Ff., blood gas analysis, 401

oxyhaemoglobin, 401

588

PHYSIOLOGY

ROBERTSON, haemolymphatic glands,

557
ROBERTSON, T. B., infusoria, 90

protein synthesis, 40, 41
ROEVER, cardiac vagus, 336
ROHMANN, glycolysis of blood, 127
ROHRIG, fats of blood, 130
ROKITANSKI, spinal respiratory centres,

447

ROLLESTON, diastole, 209
ROLLET, hydrodynamics, 235

red blood-corpuscles, 105, 121
ROMBERG, embryonic heart, 308

myogenic theory, 314
ROSENBACH, blood and respiratory
rhythm, 486

periodic respiration, 501
ROSENHEIM, glucose and heart, 338, 339

protagon, 41
ROSENSTEIN, quantity of lymph, 514

blood and respiratory rhythm, 476
ROSENTHAL, cardiac vagus, 324

eupnoea, 471

experimental apnoea, 475

general physiology, 90

inspiratory muscles, 410

intercostal muscles, 410, 414

intrathoracic and intra-abdommal
pressure, 427

phrenograph, 416

pulmonary vagus, 462, 503

respiratory capacity, 423, 439

respiratory centres, 468

respiratory quotient, 399

superior laryngeal and respiration,

465

Ross, H. C., leucocytes, 122
ROSSBACH, asphyxia and heart, 304

cardiac vagus, 218

oxygen and heart, 293
ROTH, circulation, 161

Vesalius, 179

ROUANET, heart sounds, 196
ROY, accelerators of heart, 330

blood pressure, 245

bronchio-dilatator fibres, 442

cardiac plethysmograph, 289

cardiac systole, 182

intracardiac pressure, 201

musculi papillares, 202, 213

sp. gr. of blood, 95

splanchnic nerve, 348

spleen, 554

RUDBECK, lymphatic system, 505
RUDINGER, semilunar valves, 187
RUDOLPH, mechanics of respiration,

403
RUFUS OF EPHESUS, pulmonary vagus,

457

RUSCH, oxygen and heart, 294
RUSCONI, perivascular lymphatic, 508
RUSSEL, A. E., heart, inhibition, 338
RUTHERFORD, accelerators of heart, 329

RUYSCH, fibrin, 97

SABATIER, intercostal muscles, 411
SABBATINI, coagulation of blood, 137,

155
SACHS, solution, 58

starch formation, 58
SADLER, vaso-constrictors, 349
SALKOWSKI, autolysis, 34
SALOZ, periodic respiration, 502
SALVIOLI, marrow, 539

serous cavities, 511

spleen, 550, 552
SANDMANN, bronchi, ,442
SARPI, venous valves, 165
DE SAUSSURE, plant metabolism, 54
SAVALIEW, t hymns, 542
SAVIOTTI, vascular rhythm, 343
SCHAFER, E. A., blood, 121

physiology, text-book, 9, 12

red blood-corpuscles, 102

spleen, 546, 554, 558

vagus, 558
SCHENCK, cell theory, 12

respiratory gases, 389
SCHENK, H., botany, 62
SCHERER, xanthine bases of plasma, 130
SCHIFF, M., blood-vessels, active move-
ments, 341, 367

bronchial muscles, 442

hemi-section of spinal cord, 452, 503

respiratory centres, 444, 446, 452

spleen, 553

vascular tone, oscillation, 500

vasomotor centres, 362, 364
SCHIFF, cardiac vagus, 322, 327, 329,
337

cervical plexus, 349

periodic respiration, 494

vaso-constrictor nerves, 349
SCHIMPER, botany, 62
SCHLEIDEN, cell theory, 12
SCHLESINGER, vasomotor centres, 364
SCHLOESING, blood gas, 387
SCHMALTZ, pycnometer, 95
SCHMIDT, A., blood, 155

blood gases, 386

coagulation, 134, 135

extraction of gas, 380

salted plasma, 125
SCHMIDT, C., mineral matter of plasma,

131

ScHMiDT-MtiHLEiM, peptone blood, 124
SCHMIEDEBERG, accelerators, 327, 338

tissue respiration, 393
SCHNEIDER, E. C., blood pressure, 284
SCHNEIDER, doctrine of descent, 62
SCHRODER, urea and heart, 297
SCHROFF, respiratory centres, 447
SCHULTZ, cube of, 111

heart, 340
SCHULTZE, W. H., cell, 13

chemical stimuli, 73

INDEX OF AUTHOES

589

SCHULTZE, W. H., examination of blood,
120

leucocytes, 114

red blood-corpuscles, 101

structure of protoplasm, 17

temperature and plant cells, 71
SCHWANN, cell theory, 12
SCHWARTZ, foetal apnoea, 478
SCHWEIGGER-SEYDEL, serous cavities,

509
SCOTT, F. H., phospho-proteins, 24

phosphorus metabolism, 41
•. phosphorus reaction, 39
SCUDAMORE, blood gas, 377
SCZELKOW, blood gas, 380
S£E, M., auriculo- ventricular valves, 191
SEEGEN, expired air, 397
SEEHMANN, C., muscular work, 470
SEEMANN, haemolymphatic glands, 557,

558

SEGUIN, respiration, 375, 400
SEIFERT, osteomucoid, 40
SELENSKI,. marrow and spleen, 539

spleen, 552, 585
SEMOX, laryngeal respiratory move

ments, 421
SENAC, auriculo-ventricular valves, 192

circulation, 160

heart beat, 225

intercostal muscles, 411
SENEBIER, green plants, 54

respiration, 375, 400
SERTOLI, blood gas, 385
SERVETUS, circulation, 160
SETSCHENOW, blood gas, 380, 385
SEVERANU, splenectomy, 555
SEWALL, depressor, 335
SHBREINQTON, .locomotion and nervous

system, 367, 466

SHORE, non-coagulable lymph, 513
SIBSON, thoracic respiration, 417

thoracometer, 415, 439
SIEBERT, periodic respiration, 501, 504
SIEWERT, isolation of heart, 292
SIGHIUELLI, automatic control of re-
spiratory rhythms, 460

inspiratory centres, 456, 504
SILVIO, Vesalius, 163
SIMON, blood, 94
SKODA, heart beat, 225
SMIRNOW, periodic respiration, 494

vasomotor centres, 366
SMITH, G., phototropism, 90
SMITH, LORRAINE, oxygen of blood,

391, 400

SNELLEN, vascular reflexes, 356
SOKOLOW, periodic respiration, 495, 501,

504

SOLLMANN, T., resuscitation of heart,
339

vasomotor centre, 368
SOLTMANN, vagal tone, 337
SOMMERBRODT, cardiac vagus, 336

SPALLANZANI, anabiosis, 66

arterial pulse, 277

circulation, 341

circulation in capillaries, 172

respiration, 375, 400

science of life, 3
SPALLITTA, depressor, 335

vascular reflexes, 375
SPALTENHOLTZ, thoracic skeleton, 407
SPIGEL, intercostal muscles, 412
SPIRO, muscular work, 470
SPRENGEL, circulation, 165

diastole, 208
SPRING, active diastole, 213

presystole, 181

STAEDELER, urea and heart, 297
STAHL, phlogiston, 374
STAHL, E. , chemotaxis, 74

rheotaxis, 76

STANLEY, 0. 0., blood platelets, 121
STANNIUS, heart, 299, 337
STARLING, accelerators, 330

cardiac vagus, 326

intracardiac pressure, 201, 207

lymph formation, 520, 527, 557

systolic plateau, 206
STEFANI, automatic control of respira-
tory rhythm, 460

cardiac vagus, 218, 326

diastole, 209, 231

respiratory centres, 456, 504
STEINER, arterial pressure, 243

depressor, 335
STENBECK, cardiac vagus, 333

depressor, 335

vasomotor centres, 364
STERN, terminal respirations, 452
STEWART, G. N., bulbar centres, 504

haemolysis, 122, 156

red blood-corpuscles, 121
STIENON, normal physiological solution,

295
STILLING, active movements of vessels,

341
STIRLING, W., lymph-sac, 558

myocardium, 318, 321

normal physiological solution, 295
STOKES, heart- beat, 222

periodic respiration, 492
STOPPATO, thyrnus, 545
STRASBURGER, botany, 62

chondrioderma, 16

myxomycetes, 15

phototaxis, 78

tradescantia, 18

STRASSBURG, tissue respiration, 395
STRAUB, normal physiological solution,

297

STRECKER, oxygen and heart, 294
VAN DER STRICHT, megacaryocytes, 538,

557
STRICKER, accelerators, 329, 337

vasomotors, 355, 364, 367

590

PHYSIOLOGY

SURMAY, auriculo - ventricular valves,

192

SVEHLA, thymus, 545
SWIFT, J. B., vasoniotor centre, 368

TALMA, blood pressure, 245

heart sounds, 197

TANGL, osmotic pressure of blood, 144
TAPPEINER, quantity and pressure of

blood, 255
TARCHANOFF, cardiac vagus, 324

spleen, 554

TAROZZI, anaerobic organisms, 68
TARULLI, thymus, 542, 558
TAWARA, auriculo-ventricular bundle,

314
TAYLOR, A. E., protamiries, 41

protein synthesis, 40
TEBB, M. C., protagon, 41
TEDE.SCHI, spleen, 551, 556, 558
TENNER, asphyxia, 479
TERNE VAN DER HEUL, cardio-pneu-

matic curves, 228
TERRY, O. P., galvanotropism, 90
THANE, diaphragm, 410

sternum, 410

THANHOFFER, cardiac vagus, 323
THEBESIUS, automatic control of heart,
211

semilunar valves, 187
THIRY, experimental apnoea, 476

vasoniotor centres, 327, 362, 367
THOMAS, diapedesis, 115
THOMA-ZEISS, haemocytometer, 102
THOMPSON, marine biology, 81
THOMSON, ALLEN, heart, 181

respiratory muscles, 410, 411, 412
TIEDEMANN, blood gases, 377
TIGERSTEDT, area of capillary system,
263

automatism of heart, 306

blood pressure, 246

cardiac vagus, 218

circulation of blood, 161, 231

circulation time, 283

haemodromometer, 257

heart beat, 231

heart, work, 230

intersystole, 202

recording spirometer, 425

respiratory gases, 390

semilunar valves, 190

vascular reflexes, 358

velocity of blood, 263
TIMOFEEW, accelerators, 337

cardiac vagus, 333
TISSANDIER, balloon ascent, 72
TIZZONI, splenectomy, 555, 557, 558
TOLLIN, circulation, 160, 166
TORELLE, E., phototaxis, 90
TORRICELLI, hydrodynamics, 233
TORUP, blood gases, 385
TOWLE, E. W., heliotropism, 90

TRAMBUSTI, erythroblasts, 536, 557

megacaryocytes, 537
TRAUBE, artificial cells, 147

cardiac vagus, 332

inspiratory muscles, 410

oscillations of vascular tone, 500

periodic respirations, 494, 498, 529

pulmonary vagus, 462

vasoniotor waves, 344
TREMBLEY, regeneration, 84
TREVES, pulmonary vagus, 463
TREVIRANUS, biology, 1
TRIPIER, cardiac vagus, 324
TROMMER, sugar reaction, 36
TSCHERMAK, depressor, 335
TSOHIR.TEW, accelerators, 337
TSHUEWSKY, velocity of blood stream,

284
TURNER, heart sounds, 196

USTIMOWITSCH, vasoniotor centres, 366

VAHLEN, potassium in the cell, 39
VALENTIN, active vascular movement,
341

velocity, capillaries, 263
VALSALVA, mechanics of thoracic move-
ments, 429, 436

sinus, 187

VALVERDI, circulation, 161
VANLAIR, vascular reflexes, 357

vasoniotor centres, 366
VAUQUELIN, extraction of gas, 377
VELLA, splenectomy, 557
VERNON, H. M., erepsin, 35

tissue respiration, 401
VERWORN', biogen hypothesis, 90

centres and oxygen, 394

chemical stimuli, 74

galvanotaxis, 80

general physiology, 39, 87, 90

muscle, relaxation, 214

phenomenalism, 7

stentor, 15

thalassicolla, nucleus, 14

thermotaxis, 78

thigmotaxis, 76
VESALIUS, artificial respiration, 403

circulation, 162

diastole, 208

foetal apnoea, 478

intercostal muscles, 411

semilunar valves, 187
VESLING, circulation, 166

intercostal muscles, 411
VIAULT, red blood-corpuscles, 105
VIERORDT, auriculo-ventricular valves,
192

blood pressure, 245

circulation time, 283

expired air, 397

haemocytometry, 102

haemorrhage, 152

INDEX OF AUTHOES

591

VIERORDT, haemotachometer, 274

mechanics of respiration, 439

spectrophotometer, 111

sphygmograph, 264

tidal air, 423

velocity in capillaries, 263
- work of heart, 233
VIEUSSENS, auriculo-ventricular valves,
, . 192

annulus of, 328, 354
VINCENT, haemolymphatic glands, 557

558

VINCI, LEONARDO DA, respiration, 370
VIOLA, serum, electric conductivity,

150, 155
VIRCHOW, cell theory, 12

haematoidin, 109

inflammation, 175

spleen, 552

VOGEL, blood gases, 377
VOIT, accelerators, 329

blood gases, 387

negative pulse, 227
VOLKMANN, blood pressure, 253, 283

haemodromometer, 257

haemodynamics, 283

ribs, 408

respiratory centres, 444

velocity in capillaries, 263

work of heart, 233
Voss, circulation, 166
DE VRIES, H., molecular concentration,
141

mutations, 51, 63

species and varieties, 63
VULPIAN, splanchnic nerves, 348

vascular reflexes, 359

vasomotor nerves, 348, 354, 367
VULPIUS, spleriectomy, 555, 558

WAGNER, accelerators, 337

cardiac vagus, 323

circulation, 174

pulmonary vagus, 462
WALAEUS, circulation, 166
WALDEN, E. C., normal physiological

solution, 338
WALDENBURG, blood pressure, 245

gasometric apparatus, 484

mechanics of respiration, 439
WALLACE, A. R., Darwinism, 63
WALLER, A., cardiac vagus, 329

cervical sympathetic, 342, 348

diapedesis, 175
WALLER, A. D., cardiac vagus, 322

periodic respiration, 493

sphygmograms, 266

thoracic respiration. 417
WALSCHE, thoracic respiration, 417
WALTER, blood gases, 380
WARD, R. O., alveolar air, high

altitudes, 439
WARREN, vasomotors, 352

WASILEWSKY, cardiac vagus, 323
WASILIEFF, cardiac vagus, 333
WEBER, E. H., auriculo - ventricular
valves, 192

blood-vessels, active movements, 341

cardiac centres, 336

cardiac vagus, 322, 337

mechanics of respiration, 436

muscle, elasticity, 347

quantity of blood, 98

sphygmographic waves, 240, 282

velocity in capillaries, 263

wave theory, 283
WEBER, W. , cardiac vagus, 322

wave theory, 283
WEBSTER, heart sounds, 197
WEDEMEYER, mechanics of thoracic

movements, 429

WEIDENREICH, haemolymphatic glands,
557

red blood-corpuscles, 121
WEIGERT, fats in blood, 127
WEISS, lymph, 516
WEISSMANX, heredity, 49, 62
WELCKER, haemocytometry, 102

quantity of blood, 99, 121
WELDON, origin of species, 63
WELLS, H. G., autolysis, 40
WENCKEBACH, venous pulse, 203
WERTHEIMEU, respiratory centres, 448,

451

WHEATSTONE, bridge of, 150
WILLCOCK, E. G., amino-acids, 40
WILLIAMS, heart sounds, 197
WILLIAMS, cardiac vagus, 218

tonographic apparatus, 288
WILLIS, R., circulation of blood, 179
WINOGRADSKY, nitrification by bacteria,

58

WINSLOW, auriculo-ventricular valves,
192

intercostal muscles, 411
WINTER, erythrocytes, isotonic solu-
tion, 106

molecular concentration of blood, 143,

155

WINTERSTEIN, nerve centres and
oxygen, 394

heart oxygen, 294, 338

true apnoea, 491
WINTRICH, heart sounds, 197
WOLFFBERG, pulmonary catheter, 388
WOLLASTON, muscle sound, 197
WOODWORTH, R. S., contraction of

heart, 338

WOOLDRIDGE, depressor, 334
WoRM-MuLLER, transfusion of blood,

152

WRIGHT, A. E., bactericidal power of
blood, 156

coagulation of blood, 140, 156

YEO, oxygen and heart, 293

592

PHYSIOLOGY

YERKES, R. M., entomostraca and light,
90

ZACCAIIELLI, splenectomy, 555

ZANETTI, seromucoids, 126, 129

V. ZIEMSSEX, afferent fibres of heart,

. 335
ZUNTZ, aeapnia, 475, 504

ZUNTZ, blood gases, 380, 386, 400

dyspnoea, 470

foetal blood, 477

periodic respiration, 501, 504

pulmonary gas exchange, 392, 400

reaction of blood, 96

work of heart, 230
ZWEIFEL, foetal blood, 477

END OF VOL. I

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