COLUMBIA LIBRARIES OFFSITE

HX64089460
IM QP34 .St22 1907 Elements ol human pti

RECAP

ColumtJia ®[nitlergitp^'^^K
in tije Citp of ^eto l^orfe

COLLEGE OF PHYSICIANS
AND SURGEONS

r

Reference Library

Given by

ELEMENTS

OF

HUMAN PHYSIOLOGY

BY

BENE ST H. STARLING, M.D.Lond., F.K.C.P., F.E.S.

JODRKLL PROFESSOR OP PHYSIOLOGY, DSIVKRSITY COLLEGE, LONDON

EIGHTH EDITION

CHICAGO
W. T. KEENEK & CO.

90 WABASH AVENUE
1907

Printed in Great Britain

PKEFACE

In this book I have endeavoured to present m the shortest
possible compass the essentials of the science of Phj-siology,
such as every medical student should be more or less
acquainted with. Although a few histological illustrations
are introduced, the descriptions have been kept as short
as possible, their object being merely to remind the senior
student, or to give a bare idea to the junior student of
the structure of the organs in question, and they cannot
in any way replace the study of some special work in
connection with a practical course in Histology. In the
present edition only such alterations have been introduced
as have been rendered necessary by recent advances in
Physiology.

ERNEST H. STARLING.

Ilt07.

Digitized by tine Internet Arciiive

in 2010 witii funding from
Columbia University Libraries

http://www.archive.org/details/elementsofhumanp05star

CONTENTS

CHAPTER I

PAGE

Introduction . . . . 1

CHAPTEK II

The Material Basis of the Body

SECT.

1. The Sources of the Energy of the Body .... 25

2. The Proteins . . . . . . . . 30

3. The Fats ........ 4S

4. The Carbohydrates . . . . . . . . 51

CHAPTER III

The Blood

1. The Formed Elements of the Blood . . . . .57

2. The Coaeulation of the Blood . . . . . . 75

CHAPTER IV

The Conteactile Tissues

1. General Characters of Muscle .....

2. Excitation of Muscle ......

3. The Mechanical Changes that a Muscle undergoes when it Contracts

4. The Production of Work and Heat by Voluntary Muscle .

5. The Electrical Changes in Muscle ....

6. The Chemistry of Muscle .....

7. Conditions modifying the Irritability and Contraction of Muscular

Tissue ........

8. Voluntary Contraction ......

9. Other Forms of Contractile Tissue ....

87
95
102
113
119
131

140
145
149

vi PHYSIOLOGY

CHAPTER V

Nerve-fibees (Conddcting Tissues)
sect. page

159
1C2
167
177
182
187

1. General Properties of Nerve-fibres

2. Propagation along Nerve-fibres
8. Excitation of Nerves ....
i. The Conditions aiifecting the Activity of Nerve
5. Polarisation Phenomena in Nerve
<i. The Nature of the Nervous Impulse

CHAPTER VI

The Vascular Mechanism

1. The Mechanical Principles of the Circulation . . 189

2. The Changes occurring in the Heart at each Contraction . . 206

3. The Pulse 228

4. Cardiac Ehythm . . . . . . . . 233

5. Innervation of the Heart ...... 244

6. The Work of the Heart . . . ' . . . . 252

7. Innervation of the Blood-vessels ..... 259

8. The Capillary Circulation . . . . . . . 280

9. Variations in the Quantity of Blood ..... 283

CHAPTER VII

L\MPH A^•D Tissue Fluids . . 286

CHAPTER VIII

The Mechanisms of Digestion

1. General Characters of the Processes of Digestion . . 298

2. Salivary Digestion . . . . . . - - 305

3. Digestion in the Stomach ...... 316

4. Pancreatic Juice . . . . . ... 328

5. The Bile ......... 338

6. Succus entericus or Intestinal Juice . . . . - 347

7. Absorption of Foodstuffs ...... 349

8. Summary of the Changes undergone by the Food in the Alimentary

Canal • . . 360

9. Muscular Mechanisms of Digestion ..... 363

CONTENTS Vll

CHAPTEE IX

EESriRATION

SECT. PAGE

1. The Respiratory Movements . . . . . 377

2. Chemistry of Eespiration ..... . 386

3. The Regulation of Respiration . . . . . . 402

4. Effects of the Respiratory Movements on the Circulation . . 422

5. Voice and Speech ...... . . 428

CHAPTEE X

Excretion —Functions of the Kidneys and Skin

1. The Urinary Constituents and their Origin in the Body . . 434

2. The Secretion of Urine . . . . . . . 454

3. Micturition ....... .467

4. The Skin . ....... 473

CHAPTEE XI
Fate of Foodstuffs in the Organism — Metabolism

1. Protein Metabolism ...... . 478

2. Formation of Fat . . . . . . . . 485

3. History of Carbohydrates in the Body .... 489

4. The Source of Muscular Energy . . . . . . 497

5. Animal Heat ....... . 500

6. The Normal Diet of Man . . . . . . . 507

CHAPTEE XII

The Ductless Glands . . .513

CHAPTEE XIII

Special Senses

1. On Sensation in General . . . . • ■ • 522

2. Cutaneous Sensations ...... • 526

3. Sensations of Movement and Position . . . . . 531

4. Taste and Smell ...... .539

5. Hearing . . - . • • • . . 544

6. Vision ......•• - 550

vm PHYSIOLOGY

CHAPTEE XIV

The Spixal Cokd

SEC'i'. I'AGE

1. Structure and Tracts of the Cord ..... 582

2. Paths of Impulses in the Cord . . . . . . 603

3. The Cord as Reflex Centre . . . . . .606

CHAPTEE XV

The Bkain

1. The Structure of the Brain . . . . . . 612

2. Summary of the Connections and Functions of the Cranial Nerves 634

3. Functions of the Cerebral Axis ..... 642

4. Cerebral Hemispheres . . . . . . . 653

n. The Vascular and Lymphatic Arrangements of the Central Nervous

System ....... . 6C6

CHAPTEE XVI

The Visceral or Autonomic System of Nerves . . 670

CHAPTEE XVII

Eeproduction .... 685

APPENDIX

A Description of some Electrical Instruments used in

Physiology ...... • 694

INDEX 709

PHYSIOLOGY

CHAPTER I
INTRODUCTION

Physiology is the science of the phenomena of living organisms
and of the laws regulating those phenomena. In its wider
sense it will thus include the phenomena of all vegetable
and animal life.

In this work however our immediate object is the phy-
siology of man. Now in physiology, as m all other sciences,
the only sure foundation of knowledge is that gained by
experiment ; and since ethical considerations prevent our
experimentmg on our fellow-creatures, we find ourselves
again and again forced to judge of the functions of men by
analogy with those of lower animals on whom we can experi-
ment. We can however learn many things from experiments
which we may make on ourselves, and which do not necessitate
any mutilation or involve any danger.

We find means moreover of checkmg the results of our
experience m lower animals by studymg the disorders of
function caused in man by lesions of the various parts of the
body, which we may observe m the wards and post-mortem
room. Nature however rarely limits her experiments on our
bodies to one function or organ, so that in most diseases we
have such a complexity of disturbances that this method of
investigation used by itself is apt to lead to many erroneous
deductions.

The phenomena that we commonly associate with the
possession of life are those of movement and, in the higher
animals, of warmth.

Thus, in men, some part of the body is always in motion,
and even in sleep the rhythmic respiratory movements still

1

2 PHYSIOLOGY

betoken to us the presence of life. If wg see a frog on the
ground, we instinctively poke it to see if it is alive, knowing
that if alive it will respond to the stimulus and jump away.

This property of reaction to stimulus, or irritability, is
fundamental and common to all living beings. We shall
have to consider it more in detail later on.

Then again a living man is warm, and in temperate
climates always warmer than the surroundmg air. By means
of the thermometer it is found that a healthy man's tempera-
ture is 98-4° F., and is maintained constantly at this point.
The temperature of the surrounding medium being nearly
always below this point, it is evident that the body must be
continuously losing heat and raising the temperature of sur-
rounding bodies.

Thus we see that a living body is continuously losing
energy, which may appear as work done on, or as heat
imparted to, some external object.

Yet we know that an animal continues to perform work
and to give off heat durmg the whole of its life, so that it
must have some source from which to draw its energy. This
source is the food.

Common experience teaches us that a man, to live, must
eat, drink, and breathe. His food consists of certam bodies
which we call proteins, carbohydrates (including starches
and sugars), and fats. Of these three classes, the proteins
(which exist in large quantities m meat) are essential to the
maintenance of life, though life is supported more advan-
tageously if the other two classes are also made use of.

The proteins contain carbon, hydrogen, nitrogen, oxygen,
and a small proportion of sulphur. Carbohydrates and fats
contain carbon, hydrogen, and oxygen only.

All these foodstuffs are said to possess potential energy.
This simply means that they can combine with a further
proportion of oxygen to form more stable compounds, and
in so doing set free a certam amount of energy. This energy
may appear in the form of heat, or we may use loaves or
sugar or fat to feed an engine furnace with, and so convert
the energy into work.

It is the oxidation of the foodstuffs, the burning of them
to form CO2 and water, that gives rise to the energy which
appears in the animal body either as work or heat.

INTRODUCTION 3

The oxygen necessary for this combustion is furnished
by the atmosphere. With every breath we take in oxygen,
with every breath we give out carbon dioxide and water.

Thus we may compare the animal body to a heat engine.
The fuel, the source of energy, is represented by food. The
inlet for the draught of air and the outlet for the waste
gases, the products of combustion, are both combined in one
organ, the lungs, which we use to take in oxygen and give
out C0_, and water ; and just as the coal used in engines has
some mcombustible constituents which remain as ash and
have to be raked out, so there are parts of our food which
the body cannot make use of, and which leave the body as
excrementitious matter or fseces, having passed through the
alimentary canal without at any time having formed part of
the tissues. There are still two constituents of foodstuffs
which have to be got rid of after the elimination of CO2 and
HjO by the lungs — namely, the nitrogen and sulphur con-
tamed in the proteins. This f miction is served by the
kidneys. The nitrogen is combined m the body with carbon
and oxygen to form a substance called urea, and in this form
is excreted by the kidneys, together with salts and water, as
urme. The sulphur is oxidised to a sulphate, and m this
form also appears m the urme.

We must mention here that water and salts are indis-
pensable and mvariable components of the food. Neither
of these possesses any potential energy, but they are essential
constituents of all livmg substances, and must be taken to
replace the loss of them from the Imigs, skin, and kidneys,
the water formed m the body by the oxidation of the
hydrogen of the foodstuffs being far too small to compensate
this loss.

The income and output of the body may be arranged in
the form of an equation —

Food + oxygen taken up = faces + nCO., + 7iH.O + urea ^CO<^^E;-'\ ;

and in the same way we may make an equation of the
income and output of energy —

Energy set free by burning of food to COj, H.,0, and urea
= work done by body + heat given off.

The truth of these equations has been proved by many
elaborate observations both on animals and men.

4 PHYSIOLOGY

Thus from one point of view ph^^siology may be regarded
as the history of all the changes undergone by the food m
its passage through the body, and the mechanisms by which
its potential energy is transformed into the kinetic energy of
the various vital manifestations.

But til is analogy with the heat engine must not ))e pushed
too far. In this the fuel, the source of energy, is always
distinct from the machinery by which its energy is converted
into work. In the body it is otherwise. The food that we
take in is digested, assimilated, and built up to form part of
the living framework of the body. This living stuff at the
same time takes up oxygen, so that a molecule is formed
containing all the elements necessary for evolution of energy.
Under certain conditions the foodstuffs and the oxygen in the
living molecule combme together, the unstable living molecule
of high potential energy splitting up to form stable compounds
with lower potential energy, a certain amount of energy in the
form of heat or work being rendered kinetic or actual in the
process. So the changes that the foodstuffs undergo in
their passage through the body may be divided into two main
stages :

(1) Assimilative or anabolic changes. — The food that is
absorbed from the alimentary canal, and the oxygen that is
taken in through the lungs, are built up into and become
actual constituents of the livmg protoplasmic molecule.
These processes, which are spoken of under the term ana-
holisDi, are associated with evolution of very little energy ; or
it is possible that energy may become latent in the process, the
building up being effected at the expense of some previously
formed unstable compound.

(2) Dissimilative or hataholic changes. — These are the
changes which are always associated with activity, that is,
with the manifestation of some form of energy (heat, work,
electrical change, etc.). The molecule of protoplasm breaks
down, most of the atoms arranging themselves to form the
stable compounds, CO9, water, and perhaps urea, just as a
molecule of nitro-glycerin when struck explodes with great
evolution of heat, and with the formation of stable and more
simple molecules. But in the living body the explosion is
rarely (under physiological conditions) complete. There is
always a remainder which does not undergo decomposition,

INTKODUCTION 5

and which we endow with the attribute of living, smce it
possesses the power of self-restitution, and can take up food-
stuffs and oxygen, and so build itself up again into the same
unstable molecule as before, ready to break down in part and
give rise to kmetic energy.

These changes of breaking down of a highly complex
livmg molecule, with the evolution of energy, are spoken of
under the general heading of kataholism.

Before treatmg these processes any further, we must pause
awhile to consider the manner in which the body is built up,
and what are the essential morphological characters common
to all forms of life. This miity in the structural basis of all
living beings will be seen better after a study of one of the
simplest forms ; and as a type of these we may take the well-
worn example of the amoeba.

This is a mmute organism of variable size, found in stag-
nant water and in damp earth. If we examine it under the
microscope we find that it consists of a small lump of trans-
parent material, which can be shown by chemical tests to
belong to the protein group of bodies. But it is distmguished
from a mass of inert protein by the facts that it is able to
ingest and digest food and build it up into its own substance,
that it can move about from place to place, responds to
stimulation by contractmg up into a round ball, and has the
power of reproduction by fission — that is, one amceba divides
into two mdividuals exactly similar to the parent organism
and to one another ; m short, this little lump is alive.

We find that there is some trace of differentiation even in
this primitive organism. Thus towards the centre of the
lump is a spherical or oval body (a nucleus), differmg slightly
in its chemical characters from the surroundmg substance,
which latter may also be differentiated into an mner granular
or spongy portion, the endosarc, and a peripheral hyaline
material, the ectosarc.

The stuff' composing the body of the amceba and endowed
with vital properties is called protoijlasm.

The term ' protoplasm ' has been used m two senses. By
histologists it is confined to a substance fomid in livmg bodies,
or bodies that were once alive, and reacting in certain ways
with certain stains and reagents. In this book however,
we shall use the term as a convenient expression for the

6 PHYSIOLOGY

substance forming the active living basis of all our tissues,
although analysis may show considerable differences in its
chemical composition in various organs. Protoplasm is in
fact living stuff.

The little mass of protoplasm enclosing a nucleus is called
a cell. Since however there are living organisms m which

Fig. 1.

Figure of amoeboid corpuscle, blgbly magnified, showing elongated
nucleus, endosarc, and ectosarc (Schafer).

no trace of a nucleus is to be discovered by the most improved
methods, we do not regard its presence as essential to our
conception of a cell.

Now we find that all the higher animals, includmg our-
selves, are made up of enormous aggregations of similar
nucleated masses of protoplasm, and may be regarded as
colonies of amoebae. But just as m a colony of men, with
increasmg growth of the community there is increasing
differentiation of function, so in us some cells are eminently
assimilative and digestive, others respiratory, others motile,
while some are set apart for the purposes of reproduction.

Hand in hand with this physiological goes morphological
differentiation — that is, the structure of each group of cells
becomes modified to fit it for carrying on its own work and
its own work alone.

Thus the motor cells do all the external work required by
the whole organism, both for purposes of defence and offence.
Under this latter head we may class the work of getting
food, since this must always be at the expense of some other
livmg organism. In return for this they are supplied with
food, water, and oxygen in an assimilable form by the activity

INTEODUCTION 7

of other groups of cells, just as a soldier — the community's
instrument of offence and defence — is clothed, fed, and housed
at the expense of the community for which he works.

A collection of cells, modified and built up together for
some particular fmiction, is called an organ when we are
considering its physiological import, or a tissue when we
regard only its morphological aspect.

The Assimilation of Food

In some of the lowest forms of animal life, food can be
taken in at any part of the surface of the body. In the
amoeba we can observe the whole process with the microscope,
and we see how the particle of food that has been taken in
undergoes partial solution — that is to say, part of it disappears
and apparently becomes built up mto the livmg stuff of the
organism. The remnant that cannot be dissolved is again
turned out of the body through any part of the surface.

The processes by which these mmute animals assimilate
food are very similar to those taking place in man and allied
forms, only m the latter we find that there is a differentiation
of fmiction, a division of labour in which some cells of the
body take up one part of the work of assimilation, while other
cells are told oft' to carry on another part ; and we are able to
study the whole process much more fully since we can take it
bit by bit. In man the work of taking up food is still per-
formed by the surface of the body, but it is a special part of
the surface, highly differentiated, and protected by its position
and certam mechanisms from coming in contact with anything
except food, so that it may devote its whole energies to this
one function.

All the higher animals may be considered as built in the
form of a tube, the external surface of which is differentiated
for purposes of defence, and therefore forms also the organs
by which the processes of the body act in harmony with
changes in its environment.

The mternal surface, on the other hand, is the special
alimentary surface, and is called the alimentary canal.

Between these two surfaces the wall of the tube contains
the supporting tissues of the body, the bones, etc., and also
the organs for the conversion of the potential energy of the

8 PHYSIOLOGY

food into motion and work, the muscles. In all the higher
animals cavities are developed between the two surfaces in
the substance of the middle layer — the body-cavities, repre-
sented in man by the pleural and peritoneal cavities ; so that
the alimentary canal for a considerable part of its course is
connected with the body-wall only by one side, and seems to
hang down mto the peritoneal cavity.

The tube of special alimentary cells formmg the digestive
canal is surrounded by motor cells derived from the middle
layer. These serve to drive the food from one end to the
other, and to expel the innutritions matter.

In order to get a greater number of working cells, there
are recesses of the surface lined with cells, which are called

Fig. 2.

h
Diagram showing relations of embryonic layers, e. Epiblastic or
outer layer, h. Hypoblastic or alimentary layer, m. Mesoblastic
or middle layer, b. Body cavity, n. Central nervous system.
al. Alimentary canal.

glands, and protuberances in the lumen of the tube, which
are called villi. Even among the cells of the alimentary
surface there is difierentiation of function. Thus the cells of
the glands manufacture and pour out fluids, varying in com-
position and action at different parts, which have the power
of moistening and dissolving the constituents of the food,
while the cells covering the villi seem more especially adapted
for absorbing the food after it has been digested and rendered
soluble. The glands may be simple tubular recesses in the
mucous membrane, or may branch to such an extent as to
form a bulky organ. The liver is a type of such an overgrown
process of the alimentary epithelium. This latter organ,
however, has othe]' imjDortant functions to perform besides the

INTRODUCTION 9

mere solution of foodstuffs. It is to a large extent concerned
in further elaborating the foodstuffs after they have been
absorbed into the body, so as to make the function of self-
nutrition still easier for the other servants of the organism.

We may here run through the various parts of the alimen-
tary canal, with the glands openmg into it. From the mouth,
where the food is chiefly broken up by the teeth and moistened
by the saliva, which is secreted by the salivary glands, the

Fig. 3.

Diagram of alimentary canal, m. Mouth with salivary glands, s,
opening into it. ce. (Esophagus, st. Stomach, d. Duodenum with
pancreas, p, and liver, 1, opening into it. int. Small intestine,
cffi. Caecum, c. Colon, r. Eectum. a. Anus.

food passes through the tubular oesophagus or gullet into the
stomach. This is a saccular dilatation of the canal, situated
in the upper part of the abdomen. In it the foodstuffs are
acted upon by the gastric juice, secreted by small tubular
glands, and the dissolved products are partly taken up or
absorbed.

After the stomach the alimentary canal becomes narrowed
again to form the small intestine. In man this is divided

10 PHYSIOLOGY

into three main divisions — the duodenum, aljout nine inches
long ; and the jejunum and ileum, about twenty feet long.

Into the upper part of the duodenum two glands, the liver
and pancreas, pour their juices, while the whole internal
surface is taken up with villi and tubular glands (crypts of
Lieberkiihn), so that digestion and absorption go on simulta-
neously. The ileum leads into the colon or large intestine.
This is about twice as wide as the small intestine, from which
it is separated by a valve, the ileo-colic valve. Its internal
surface is entirely taken up with tubular glands, no villi being
present. In this part of the canal absorption probably pre-
dominates over digestion. The lower part of the large intes-
tine is the rectum, and opens by an aperture, the anus, on the
surface of the body, by which the indigestible residue of the
food, forming the faeces, is discharged.

Circulation of the Blood

In order that the foodstuffs taken up by the cells lining
the alimentary canal should be distributed to all parts of the
body, there must be some means of transporting the food.
This means is furnished by the blood. All the tissues of the
body are supplied with a close meshwork of delicate tubes,
called capillaries, the walls of which are formed by a single
layer of cells. This layer is permeable to fluidsj so that the
surrounding tissues are practically in contact with the blood
in the capillary tubes, and can take up nourishment from or
give ofi' their effete material to it. These capillaries com-
municate with larger tubes which have thicker walls, and
these lead to and from a hollow organ with thick muscular
walls — the heart.

The heart is divided into four cavities, two auricles and
two ventricles, each auricle being separated from the adjoin-
ing ventricle by valves. These valves are so arranged that,
when the heart contracts and diminishes its capacity, the
blood can flow only in one direction. We may compare it to
an enema syringe in which the compressing force is in the
elastic wall instead of being supplied by the hand of the
experimenter.

The tubes taking the blood from the heart to the tissues
have thick elastic walls, and are called arteries ; while those

INTRODUCTION

11

bringing the blood back from the tissues are called veins, and
have thinner and more distensible walls.

Fio. 4.

Diagram of capillaries in frog's web.

Fig. 5 shows the course taken by the blood in its circula-
tion through the body, as it is impelled by the contracting
heart.

Diagram of circulation, l.v. Left ventricle, l.a. Left auricle.
R.v. Eight ventricle, k.a. Eight auricle, ao. Aorta, s.c. Sys-
temic cai^illaries. al. Alimentary canal, p. Portal vein. l. Liver.
H.v. Hepatic vein. p.c. Capillaries of lungs.

Starting from the left ventricle, the blood is propelled
through the aorta into the systemic arteries, and thence into

12 PHYSIOLOGY

the capillaries supplying the head, neck, body, limbs, and
alimentary canal.

From the capillaries of the alimentary canal the blood
flows into a number of veins, which unite to form a large
vessel, the portal vein. This then enters the substance of the
liver and breaks up again into a number of capillaries, which
ramify and anastomose round the hepatic cells.

The blood from these capillaries is agam collected into
a large vessel, the hepatic vein, which flows mto the inferior
vena cava. This latter vessel also conveys blood from the
back, lower limbs, and kidneys.

The superior vena cava with the blood from the upper
extremities and head and neck, and the inferior vena cava
open into the right auricle.

From the right auricle into the right ventricle, then along
the pulmonary artery which breaks up into mnumerable capil-
laries in the lungs (formmg the lesser circidation), then from
the pulmonary capillaries along the pulmonary veins, the
blood reaches the left auricle, from which it flows into the left
ventricle, having completed its whole circulation.

Bespiration and Excretion

We have hitherto spoken of the blood only as a medium
for the distribution of food to the various tissues. But it is
more than this. Every cell, every protoplasmic miit of the
body, to live, must be supplied with oxygen, and must be able
to get rid of the products of its activity, namely, CO^ and urea,
or some body allied to urea. In all these functions the blood
acts as the middleman between the cell hidden deep in the
body and the cell on the surface of the body.

Thus as the blood flows through the lungs, it is separated
from the air in the cavities (alveoli) of this organ only by
the thinnest possible layer of cells. Here we find that the
blood changes its composition, giving up COo and taking in
oxygen.

When the blood reaches the tissues, a process the reverse
of this takes place (' internal respiration '), the cells of the
tissues takuig up oxygen and giving up CO, to the blood.

The cells also discharge their nitrogenous waste products
into the blood, which immediately carries them to the kidneys.

INTRODUCTION

13

In these organs again we find a single layer of cells between
the blood-capillaries and a cavity which is in free communi-
cation with the exterior. It is these cells which take up the

Fig. 6.

Diagram of lung tissue, showing — b. Capillary blood-vessels in walls
of alveoli, e. Epithelium lining the alveoli, f. Cut edges of
alveolar walls, consisting of connective tissue fibres and elastic
tissue.

Fig. 7.

Diagram of kidney, av. Afferent blood-vessel, ev. Efferent blood-
vessel, c. Loop of capillaries, e. Secreting epithelium, u. Urinary
tubule leading to bladder and exterior.

waste products of the other tissues from the blood and dis-
charge them mto the urinary tubule, together with water and
salts, as urme. From the urinary tubule the urine flows down
the ureter into the bladder, whence it is voided periodically.
Thus the blood is contmually taking up food from the

14 PHYSIOLOGY

alimentary canal and oxygen from the lungs, and carrying
them to the tissues. Here it parts with them and receives in
return the products of tissue change (which are indeed only
the products formed by the union of the oxygen with the food-
stuffs), and carrying these away discharges them on the
exterior of the body by means of the lungs and kidneys.

Muscula?' Tissues

Retaming our comparison of the human body to a heat
engine, we have still the most important part of the mecha-
nism to consider —namely, that part in which the heat produced
by the oxygenation of the food is converted into motion and
so performs work.

This is effected by specialised groups of cells united together
to form the muscles. These are fleshy masses attached at two
ends to the bones and other supporting tissues of the body.
They are capable under certain circumstances of shortening,
that is to say, approximating the points to which their two
ends are attached against resistance, so that they do work.
Thus the biceps muscle of the arm is attached above to the
shoulder-blade, and below to the radius, one of the bones of
the forearm. When it contracts, it thickens and shortens,
and draws up the forearm so as to bend the elbow-joint.
Thus it may do work in two ways. If the shoulder is fixed,
contraction of the biceps will raise a weight held in the hand ;
or the hand may be fixed, as in hanging on a horizontal bar,
so that the effect of contraction of the muscles is to raise the
shoulders and with them the whole body.

We also find muscular tissue, though less highly differen-
tiated, in the interior of the body surrounding the heart,
blood-vessels, and alimentary canal. It is by the contraction
of these hollow muscular tubes that the blood is set in motion,
and the food propelled from one end of the alimentary canal
to the other.

Go-ordination and Reaction

Here our analogy of the heat engine must cease. For
whereas an engine needs engineers and stokers to determine
its work and keep it supplied with fuel, a man's body goes

INTRODUCTION 15

on seeking out food and feeding itself and working for sixty
or seventy years.

According as the external circumstances vary, so a man
must do more or less work, must take more or less food.
Moreover, in such a complicated mechanism as the human
body, there must be a delicate adjustment of the actions of
the various organs to one another, so that the part which is
doing most work should be best supplied with nutriment and
oxygen, and no part waste its stored-up energies in doing
useless work.

Thus there is an adaptation of the actions of the body as
a whole to the requirements of its environment ('necessity '),
and also mutual adaptation within the body of the actions of
the various organs to one another. This harmonious working
of the body and all its parts is effected by the governing and
directing power of the central nervous system, the brain and
spinal cord of all the higher animals.

In comparing the human body to a tube, we alluded to
the outer layer of cells as especially set apart for the purpose
of protection, and for regulating the events of the body
according to the changes in the environment. Very early
in develoi^ment however, we find that a part of this surface
becomes involuted into a groove, the walls of which close
over so as to form a canal — the primitive neural canal.
The latter then becomes cut off for most of its extent from
the external surface by an mgrowth of the middle layer or
mesoblast.

The cells formmg the walls of the canal grow and mul-
tiply, so that finally the canal is extremely mmute in propor-
tion to these walls.

The spmal cord retains this primitive form of a canal
with thick walls. At the anterior end of the body (head
end) this canal becomes dilated, and sends out lateral and
mesial prolongations. The walls of these also become
thickened at some places and thinned at others, so that finally
a bulky complicated organ is produced which we call the
brain.

In figs. 8, 9, and 10 the different parts of the central
nervous system are shown diagrammatically, and from these
the origin of the whole brain and spinal cord from a simple
canal pinched off from the epiblast will be evident.

16

PHYSIOLOGY

But this tube of specially ' reactive ' or, as we shall always
call them, nerve-cells, still remains connected with the
periphery by strands of protoplasm which we call nerves.

Fig. 8.

Diagrams showing formation of the nervous centre (brain and spinal
cord) by a tuclcing-in of the outer or epiblastic layer, e. Epiblast.
m. Mesoblast. h. Hypoblast, n.c. Neural canal, n.g. Neural
groove.

These strands in many cases end close under the surface of
the skin in various forms of cells, specially differentiated for
feeling different kinds of stimuli.

Fig. 9.

Diagram of the cerebral vesicles of the brain of a chick at the second
day(Cadiat). 1,2,3. Cerebral vesicles. 0. Optic vesicles.

By this means the central system may become aware
of all the changes occurring at the periphery of the body.

INTRODUCTION

17

But it is necessary that the organism should be able to
react to changes m its surroundings, and we find that very
early in the development of the body certain cells in the
wall of the tube send out long protoplasmic processes which
become connected with the muscles, glands, heart, and blood-
vessels. Through these processes impulses descend from the
brain or spmal cord in response to stimuli which have pro-
ceeded up the sensory nerves from the periphery.

This change in the intra -corporeal events determined by a
change in the extra-corporeal through the intervention of the
central nervous system is called a reflex action. The meaning

Longitudinal section through brain of chick of ten days (after
Mihalkoviez). olf. Olfactory lobes. h. Cerebral hemisphere.
Iv. Lateral ventricle, pin. Pineal gland, bg. Corpora bigemina.
cbl. Cerebellum, o.c. Optic comniissure. pit. Pituitary body,
pv. Pons Varolii, m.o. Medulla oblongata, v^, v^ Third and
fourth ventricles.

of this term must be carefully borne in mind, since we shall
meet with examples of it in every stage of our subject. In
fact, the whole of an animal's life may be looked upon as one
long series of reflex actions.

Perhaps the idea will be rendered more concrete by an
example. If we decapitate a frog and then dip one of its toes
into dilute acid, the leg is drawn up.

This reaction may be prevented in any one of the follow-
ing ways :

1. Section of the sensory (afferent) nerves from the toes
to the spinal cord.

2. Destruction of the spinal cord.

3. Section of the motor (efferent) nerves coming from the
cord and running to the muscles.

4. Destruction of the muscles of the leg.

18

PHYSIOLOGY

Thus the elements composmg a reflex arc are —

(1) A sentient surface (such as the skin) connected by —

(2) A sensory or afferent nerve

(3) To a cell or group of cells, or of nerve-tracts in the
central cerebro-spinal axis. This again is connected by —

(4) A motor or efferent nerve to

(5) A muscle or group of muscles.

For muscle in (5) we may substitute gland-cell or any
other cell in the body capable of responding by some change

Fig. 11.

Diagram of reflex action, e. Sensory epithelium, a.n. Afferent
nerve-fibre. s.c. Sensory cell. c.n.ft. Central nervous system.
n.r. Branch of sensory cell in close contact with processes of m.c,
motor cell. e.n. Efferent nerve-fibre, terminating in end-plates on
the muscle, m.

in its condition to a stimulus reaching it from the central
nervous system.

To fire off a reflex arc, all that is necessary is an appro-
priate stimulus applied to the sentient surface. Now we find
that m all animals almost anj^ form of energy may serve as
a stimulus. Thus it may be merely mechanical as when we
poke the frog, or chemical, or electrical, or in the form of
light, heat, or sound. In every case where a stimulus is
applied there is an expenditure of some energy, though the
amomit may be very slight — a conversion of one of those
forms of motion (of masses or molecules) into some other

INTRODUCTION 19

forms of motion which cause or attend the passage of an
impulse up the afferent nerve.

It must be noted however that the work done by the
stimuhis is in no way equivalent to the energy it sets free
reflexly. The slightest touch of a pin to the skin causes
most powerful reflex movements of the thigh muscles of a
decapitated frog. A stimulus in fact acts only by setting
free a large amount of potential energy previously stored up
in the muscles, which amount may depend on the most
diverse circumstances : just as the amount of energy set free
in firing a gun depends on the amount of gunpowder in the
charge, and not on the size of the fulminating cap used to
fire it. This simile however must not be taken too literall}'.
Under normal circumstances a stronger stimulus, within
certam limits, will give rise to a stronger evolution of energy
(contraction of a muscle, etc.) ; but in every case the work
done by the muscle far transcends in amount the work done
m stimulating the muscle.

In all higher animals it is not the whole sensory surface
that will respond to all forms of stimuli. Here agam there
is a division of labour among the sensory cells, some taking
on the function of converting light, others heat, others sound,
and so on, into a nervous impulse, which may ascend to the
central nervous system and there give rise to some form of
response as a reflex action.

Thus we have the formation of organs of special sense
containing sensory cells, which under normal circumstances
react to one form of stimulus, and only one. The eye receives
impressions of light, the ear of sounds, special cells in the
skin impressions of temperature (heat and cold), and of pres-
sure and touch.

The higher sense-organs, as they are termed— the eye,
olfactory organ, and ear — are connected with the upper part
of the neural tube, the brain. The end-organs of temperature
and touch are distributed over the whole surface of the
body, and are connected to the neural tube through its whole
length.

The spinal cord has a twofold function. It serves as a
conductor of impulses started by stimuli at the surface of the
body to the bram, and as a conductor of efferent impulses
from the brain. It may also be regarded as a collection of

20 PHYSIOLOGY

reflex centres regulating all kinds of movements and func-
tions.

The nerves, which connect the cord with all parts of the
body, are arranged symmetrically on the two sides of the
body, so that there are thirty-one pairs of nerves arising from
the spinal cord.

Each nerve-trunk at its connection to the cord is divided
into an anterior and a posterior root ; and we shall show
later on that all the impulses leaving the cord pass along the
anterior roots, while the posterior roots are composed exclu-
sively of fibres bearing afferent impulses.

A short distance from the cord these two roots join, and
the mixed nerve-trunk thus formed divides again and again,
supplymg the sensory end-organs and muscles of a definite
segment of the body.

An important branch of the mixed nerve-trunk (though
small anatomically) is the ramus communicans of the sympa-
thetic. The fibres forming this little nerve pass into a chain
of ganglia {i.e. collections of nerve-cells) situated along the
back of the body-cavity, in front of the spmal column, and
sending a prolongation up mto the neck.

Some of the fibres become connected with these ganglion
cells while others simply pass through the ganglion. All
the fibres however, before passing to their destination, become
connected with nerve-cells situated more peripherally. This
destmation is all the organs of vegetative life, the alimentary
canal, heart, blood-vessels, glands, etc.

The whole system of visceral nerves, formed from the
nerve-fibres of the rami communicantes, is called the sym-
pathetic system.

The accompanying diagram will serve to illustrate the
general plan of distribution of a single spinal nerve, and its
connections with the sympathetic system.

An unending series of reflex actions is gomg on m our
body, and of many of these we may be quite miaware. But
in very many cases we learn that something is going on when
a stimulus affects our afferent nerves by having what we call
a> feeling or sensation. In order to experience a sensation we
must be conscious, and therefore sensations are classed with
emotions, ideas, volitions, as states of consciousness.

A ]5ure investigation of states of consciousness, however,

INTRODUCTION

21

belongs to the province of the psychologist. We have only
to deal with them so far as the function of afferent nerves is
concerned, since it is difficult to obtain an objective sign of
their activity (though, as we shall see later, such signs are
present) .

We have evidence that m man and the higher animals
consciousness is intimately bound up with the outgrowths

Fig. 1-2.

Scheme of the nerves of a segment of the sijinal cord (Foster). Gr.
Grey ; w, white matter of the cord. a. Anterior ; p, posterior
root. G. GangUon on posterior root. n. Whole nerve giving off
n' somatic nerve to muscle m, or sensory cell s, and visceral
branch v, which passes through various ganglia of the sympa-
thetic system before reaching the visceral muscle m or sensory
cells, rv is the grey ramus communicans which runs back from
the ganglion 2 to the spinal cord. It gives off a branch vm,
which runs in connection with the spinal nerve to the blood-vessels
of the limbs. Sy. The sympathetic chain uniting the ganglia of
the series 2.

from the front of the neural tube, which we call the cerebral
hemispheres. On the integrity of these depends also the
carrying out of the so-called spontaneous or voluntary move-

22 PHYSIOLOGY

ments —that is to say, movements which are not, so far as we
can tell, called forth by any directly preceding stimulus or
change in the environment of the animal.

The parts of the brain below the hemispheres seem built
up on much the same plan as the spinal cord, and like this
contain a collection of reflex centres and nerve-paths. These
reflex mechanisms however are very important, since their
afferent channels are the important nerves subservmg the
functions of seeing, hearmg, smellmg, tastmg, etc.

The significance of the cerebral hemispheres in the normal
life of the animal can be well shown in the frog. If in this
animal we remove the cerebral hemispheres, we find that it
still acts in all respects as a normal frog, except that it is
incapable of interpreting its sensations or of mitiating volun-
tary acts. If we put it in water, it swims about till it comes
to the edge of the basin, when it crawls up and sits on the
edge. Stroke its back and it croaks. Put it on a horizontal
board, it remains perfectly still. Incline the board, the frog
climbs up it. All these complicated movements are brought
about immediately by changes in the environment. They are
examples of reflex action.

But if we leave the brainless frog to itself, and protected
from disturbing influences, it sits there till it becomes a
mummy. Having lost the greater part of its consciousness,
it can no longer jeel hmigry, it does not hnoio its food when
it sees it, and therefore does not loill to move in order to
get it.

Beprod'uction and Heredity

The production of new individuals, the crowning point of
an animal's existence, is carried out by means of certain
special cells, the spermatozoa in the male and the ova in the
female, which represent potentially all the peculiarities of
the parent organism. By the union and fusion of parts of
a spermatozoon and ovum, a single cell is produced, the fer-
tilised ovum, as it is termed ; and from this cell by division
and differentiation is formed the new individual, endowed
with structures and properties similar to and derived from
both parents. The rest of the cells of the body afterwards
die, havmg served their function when they have reared the
new family of individuals.

INTEODUCTION 23

Thus from a broad standpoint all the complicated pro-
cesses that we study in physiology, all the toil and turmoil
of human existence, are nothmg but ' the by-play of ovum-
bearing organisms.' The biological destiny of man is accom-
plished with the production and rearing of a new mdividual.

Now we have shown above that in many respects the body
may be regarded as a mechanism, controlled by external
circumstances, and converting the potential energy of food
into the kinetic energy of warmth and movement.

This comparison is further justified when we find that
in all processes of the body there is no creation of energy.
All energy possessed by the body is derived from the poten-
tial energy contained in the food, which in its turn repre-
sents the stored-up energy of the sun's rays.

On these accounts many have thought that no other fac»
tors were at work in livmg bodies than the intermolecular
relations which comprise the laws of physics and chemistry,
and that even the supreme facts of consciousness might be
explained in this manner. But past experience warns us to
be very careful before accepting purely physico-chemical con-
ceptions of any vital phenomena. Again and again, as we
shall see when discussmg the processes of absorption, secre-
tion, respiration, etc., have purely physical explanations been
put forward, only to be overthrown by further investiga-
tions.

In fact every cell in the body, like a conscious being
seems to have a power of selection, a power to eschew the
evil and choose the good, the good being that which is neces-
sary to its preservation as a unit of the cell community. A
layer of living protoplasm, one twenty-thousandth of an inch
in thickness, is able to take up materials on one side and
discharge them on the other, in direct opposition to all
known physical laws of diffusion and osmosis.

We may discover the functions of a living cell and the
conditions of its activity, and, m general terms, the source
from which it derives its energy ; but beyond this we have
been foiled in all attempts to find out how the cell uses the
energy of the food for its own aims. It does not at present
seem likely that any physico-chemical hypothesis will ever
explain how all the physical and intellectual peculiarities may
be transmitted from father to son through one single minute

24 PHYSIOLOGY

cell, a spermatozoon, five hundred millions of which would
hardly occupy one cubic millimetre.

We shall therefore m the following pages confine our-
selves to a discussion of the functions of the various organs,
the conditions of their activity, and the physical and chemical
changes which can be demonstrated to occur in the organs
concomitantly with their activity.

These objects of physiology are still very imperfectly
known, and probably need yet many years of laborious
research for their elucidation. But when we are fully
acquamted with the laws and conditions of the activities of
normal living structures, we shall be able to attack the pro-
blems of disease with a sure hope of success ; for, knowing
how the organism will react to all manner of circumstances,
we shall be able to put it into an artificial environment which
will counteract the effects of the previous abnormal environ-
ment, and so restore the organism to a healthy condition.

25

CHAPTER II

THE MATERIAL BASIS OF THE BODY

Section 1
THE SOUECES OF THE ENERGY OF THE BODY

Careful experiments have shown that there is no creation or
destruction of matter m the living organism, that is to say,
the principle of the conservation of matter applies withm as
without the living body. Hence an ultimate analysis of the
body reveals the same elements as are found in the earth's
crust.

The results of ultimate analysis teach us that twelve
chemical elements enter into the composition of all living
organisms. These are carbon, hydrogen, oxygen, nitrogen,
sulphur, phosphorus, chlorine, potassium, sodium, calcium,
magnesium, and iron. They are essential to the life of the
animal. Other elements, such as silicon, iodine,' fluorme,
manganese, are found occasionally, but it is not known whether
the minute quantities of these substances which are found are
merely accidental or necessary to life.

If the body of an animal be heated with free access of
oxygen, the carbon and oxygen are burnt up and escape as
carbon dioxide and water ; the nitrogen is eliminated as
ammonia or in the free state, and the rest of the elements
remain as the ash.

One hundred parts of the ash of a yomig dog contam
(Bunge) —

K,0 ....

8-5

Na^O

8-2

CaO

35-8

MgO

1-6

Fe..03

0-34

P.63

39-8

CI

7-3

1 T-ji; i_ 1 ; i-T-i- J i.:-i j.

' Iodine seems to be an invariable and essential constituent of the active
principle of the thyroid gland (vide Chap. XII.).

26 PHYSIOLOGY

Most of these constituents of the ash exist in the tissues sm
salts, either free or in a very loose state of combination with
other substances.

Nearly all the iron, sulphur, and a considerable amount of
the phosphorus however are found in the body, not as salts,
but as complicated organic compounds with proteins and allied
bodies.

The same elements are found in plants, although here
certain of the non-essential elements may occur in greater
quantities than they do in the case of animals. Thus silica
forms a large proportion of the ash of certain grasses, although
a normal growth can be obtained in the almost entire absence
of this substance.

All these elements are derived by plants from the atmo-
sphere or from the earth's crust. Here however the substances,
which present themselves as foodstuffs to the plant, are in a
state of maximum oxidation, and are devoid of potential energy,
the mineral matters occurring as salts, the carbon as the CO.^
of the atmosphere, and the nitrogen as minute traces of
ammonia or nitrites. In the plant these elements are built
up into substances which can develop energy by combustion,
and therefore are possessed of potential energy. This energy
is put into the plant by the sun's rays. The green parts of
plants are able to utilise the radiant energy of certain parts
of the spectrum in the splitting up of CO2, giving off' the
oxygen to the atmosphere, and building up the carbon into
complex compounds, of which the earliest appear to be sugar
and starch. It is supposed that the first change which occurs
is a formation of formaldehyde, CO., + H.p = CHjO + 0.,, and
that this formaldehyde by simple condensation yields a carbo-
hydrate of the formula C,;H,20,;. The plant thus obtains a
store of potential energy, which it can utilise for the formation
of still higher products or for the synthesis of such bodies
as fats and proteins. All three classes of substances, proteins,
fats, and carbohydrates, are built up together with salts and
water to form the unstable material which, as the chemical
basis of life, is known as protoplasm.

In animals this power of utilising the sun's rays for the
synthesis of complex organic substances from C0._, and nitrites
or ammonia is wanting. They are therefore dependent for
their life on the co-existence of plants. On these they feed,

THE MATEKIAL BASIS OF THE BODY 27

taking iii their food in the form of proteins, fats, and carbo-
hydrates. In the animal body these substances are oxidised,
setting free once more the energy which had been snatched by
the plant from the smi's rays, and are excreted in their original
form as CO,,, and ammonia or allied bodies such as urea.

A marked distinction thus seems to obtam between the
chemical processes in plants and animals. In the former the
processes are chiefly synthetic, while in the latter they are
chiefly oxidative. No hard and fast line however exists between
the two classes of living bemgs. The power of splittmg up
CO., is confined to the chlorophyll granules of plants. In all
other parts of plants, and perhaps in these granules themselves,
a process of respiration is also going on, in which oxygen is
absorbed and CO.^ is given ofl' ; and in the entire absence of
oxygen every plant, except certain anaerobic bacteria, dies.
Respiration therefore is a common function of all protoplasm,
and is merely hidden in green plants exposed to smilight by
the more energetic assimilative function of the chloroph3dl
granules.

Although the animal body cannot build up proteins, fats,
and carbohydrates from ammonia and COg, yet, given these
three classes of foodstufls, it can from these carry out many
complicated synthetic processes. Thus it was long ago shown
by Wohler that benzoic acid administered to an animal was
excreted in the urine as hippuric acid. In this case a synthesis
of benzoic acid with glycine (amino-acetic acid) had taken place.

C«H,.COOH + CH.,NH,COOH = C,H3.C0.CHNH,C00H + H,0.

We shall have occasion to discuss many other examples
of synthetic processes occurring in the animal body. The
best known are perhaps the formation of fats from carbo-
hydrates, and the formation of the complex conjugated pro-
teins, nucleo-proteins, etc., from the simple proteins, fats, and
carbohydrates of the food.

Although therefore we must allow to all protoplasm, whether
vegetable or animal, synthetic as well as disintegrative powers,
the fact remains that the one source of the energy of the
animal body is the disintegration and oxidation of the com-
pounds presented to it in its food. Now all substances can be
divided into two classes : those which undergo spontaneous
combination with oxygen, such as phosphorus or an alkaline

28 PHYSIOLOGY

solution of pyrogallic acid, which may be termed auto-oxidis-
able, and those which are unaffected at ordinary temperatures
by oxygen, which may be termed dysoxidisable. To the latter
class belong the foodstuffs, and the question arises, by what
means their oxidation is effected in the living body. Outside
the body we can effect a combination of these substances with
oxygen by raising their temperature to a red heat, but this
method is obviously inapplicable within the body. The diffi-
culty is that, at ordinary temperatures, molecular oxygen, Og,
is relatively inert, the combinmg affinities of each of its atoms
being satisfied within the molecule, 0 = 0. Oxidation how-
ever can at once be effected if by any means we can break up
this molecular compound, so as to leave the combining affinities
of the two compounds unsaturated. Many theories have been
put forward as to the manner in which this activation of the
oxygen is carried out in the body. Thus it has been suggested
that the total oxidation occurs, so to speak, m two stages. By
the ordinary disintegrative processes, reducing (auto-oxidisable)
substances are formed, and these combining with oxygen split
up the oxygen molecule, leaving one half of the molecule
free to attack less readily oxidisable substances. Many such
instances are known of the simultaneous progression of re-
ducing with oxidative processes. Thus ozone is formed in
the slow oxidation of phosphorus by the air. The oxidation of
pyrogallol in ammoniacal solution is associated with the con-
version of a certain amomit of the ammonia into ammonium
nitrite. Of the existence of reducing substances in the body
we have ample evidence. Thus methylene blue injected into
the living animal undergoes reduction in the tissues, forming
a colourless compound which is re-oxidised to methylene blue on
exposure to the atmosphere. It is difficult however to decide
whether these reducing substances are formed as by-products
in the cell metabolism, or whether they are an integral part
of the protoplasmic molecule, as was imagined by Pffiiger.

Closely allied to this process is the oxidation which is
associated with the splitting up of a molecule of water. Thus
if benzaldehyde is shaken up with water and air, it becomes
oxidised to benzoic acid, and at the same time can effect oxida-
tion of other dysoxidisable substances. In this case a water
molecule is split up into H and OH, the OH group taking the
place of the H in the aldehyde group (COH) of the benz-

THE MATEEIAL BASIS OF THE BODY 29

aldehyde, wliile the two hydrogen atoms set free conibine with
an atom of oxygen to form water, thus releasing an atom of
oxygen in the active state and therefore ready to effect other
oxidations.

According to other authorities, the mechanism of oxidation
m the body is similar to that employed m the manufacture of
sulphuric acid. In this case sulphur is burnt to form SO2,
and then nitric oxide, NO, is added together with air. The
NO combines with the oxygen of the air to form NO.;, and this
reacts with the sulphurous acid to form SO.j and NO. The NO
thus acts as a carrier of oxygen between the air and the SO.,.
In the same way an ammoniacal solution of cupric hydrate,
which is reduced on boiling with dextrose, becomes at once
blue again on exposure to the air, and can be used to oxidise
an indefinitely large quantity of the dextrose. In these cases
we can make precise chemical equations for the various steps
of the oxidation. In other cases this is not possible. Thus
spongy platinum will effect a rapid union of hydrogen and
oxygen to form water. Here there is no evidence of the for-
mation of an oxide of platmum as an intermediate stage of the
process, and we say that the substance acts katalytically. In
all cases however it is difficult to explain why the presence of a
third substance should render the oxidation possible. We have
here an example of a whole series of phenomena m chemistry,
where the presence of a factor, which adds nothing to the total
energy of the reaction, yet materially alters the velocity of
the reaction, often rendering a reaction possible which with-
out it would take an mfinity of time for its accomplishment.

It has been definitely shown that substances can be ex
tracted from the blood and tissues of animals and from the
substance of plants, which possess the property of effectmg
certain oxidations, and have therefore been termed oxj^gen
carriers or oxygen ferments {oxydases). The exact chemical
character of these substances is undetermined, though in some
cases they seem to belong to the class of nucleo-albumens.

It is of course possible that all these methods are made
use of in the livmg cell for the oxidation of foodstuffs. It
is certain that the oxidation is not accomplished at one
stroke, but that it proceeds by stages. It will be our office
later on to try to trace out some of these stages, and so
obtain some idea of the history of the foodstuffs in the body.

30 PHYSIOLOGY

Section 2
THE PEOTEINS

Since our chief foods are derived from other living
organisms, a consideration of the proximate constituents of
our bodies covers that of the proximate constituents of the
food. These can be divided into three main classes, proteins
which contain nitrogen and sulphur, fats, and carbohydrates.
Of these the proteins are the most important, since they repre-
sent the only irreplaceable portions of the food. Many animals
can live on a pure diet of proteins, and even in man fats and
carbohydrates are largely interchangeable ; but in no case
can the place of proteins be taken by any other substances.

Proteins are found in all protoplasm, and are more abun-
dant in those tissues where growth is actively going on. They
are, in the condition in which we generally come across them,
amorphous, indiffusible, and varying in their solubilities.
They are inert bodies, tasteless, and presenting no distinct
acid or basic characters. Although it is possible to obtain
certain proteins in a crystalline condition, they all belong to
the class of bodies known as colloids.

The term ' colloid ' was applied by Graham to distinguish certain substances
such as egg-albumen or gum or gelatin, from easily crystallisable substances
such as salts and sugars. Whereas the latter are easily diffusible through
animal membranes, colloids are absolutely indiffusible. All colloids appear to
possess very large molecules, and it is possible that their indiffusibility is con-
nected with this fact. It is difficult however to be certain that the apparent
solutions of colloids in water are really strictly comparable with such a solution
as that of sodium chloride. In many cases the apparent solution is really
only a suspension of fine particles, and very simple means will suffice to bring
most colloidal solutions into such a condition of suspension. All colloidal solu-
tions may, under favourable conditions, present the phenomenon of coagula-
tion, a phenomenon which depends on an alteration of the relations between
suspended particle and solvent, and on an aggregation of the smaller into
larger particles, which may fuse to form networks. This coagulated condition
may be brought about by various means : by the application of heat, by simple
mechanical shaking, or in some cases by the mere addition of neutral salts.
In some cases the reaction is reversible. Thus gelatin and water form a solid
jelly when cold, but become fluid when the temperature is raised. An alkaline
solution of casein, to which calcium chloride has been added, foi-ms a solid clot
when warmed, but becomes fluid again at a normal temperature ; and a similar
phenomenon is observed in the early stages of the action of pancreatic juice
on milk. In most cases however the action is irreversible. Silicic acid, which

THE MATERIAL BASIS OF THE BODY 31

has been coagulated by the addition of neutral salt, cannot be dissolved again
on removing the salt by dialysis. The coagulum which is formed in a solution
of egg albumen by heating is permanent, and insoluble in weak acids or alkalies
or in salt solutions. A colloidal membrane permits as a rule the free passage of
water and salts, but is impermeable for dissolved colloids, so that on filtering
a colloidal solution under pressure through a colloidal membrane, the filtrate
consists simply of water with salts, all the colloid remaining behind on the filter.

All proteins contain oxygen, hydrogen, nitrogen, carbon,
and sulphur, and their compositions vary round the following
numbers.

C . . . . 50*6 — 54"5 per cent.

H . . . . 6-5 — 7-3 „

N . . . . 15-0 —17-6 „

S . . . . 0-3 — 2-2 „

P . . . . 0-42— 0-8.5 „

0 . . . . 21 -50 -23 -.50 „

Of the sulphur a certain portion is oxidised, while the rest
exists in the unoxidised condition, and can be split off as a
sulphide by boiling with caustic potash or soda. Hence we
must assume the presence of at least two atoms of sulphur in
the protein molecule, and this assumption enables us to arrive
at the smallest possible empirical formuhie of many proteins.
Some of these formulfe may be given here, smce they serve to
indicate the enormous size and complexity of the molecules of
this class of substances.

Egg albumen .... C.,„jH3.,2N.20e6S-

Protein in hemoglobin (from horse) . CssoHh]!isN2io024iS.,.

(from dog) . . C;,,H„;',NJ,„02„SJ.

Crystallised globulin (from pumpkin-seeds) C.„,2H„,N,,„Os3S.^.

Crystallisation of pi-oteins. — It has long been known that proteins occur in
the crystalline form in the seeds of certain plants, as in hemp-seeds, paranut,
and pumpkin and castor-oil seeds. These crystals, which are known as aleuron
grains, consist of proteins belonging to the class of globulins. By mechanical
means they can be separated from the surrounding tissues, and after washing
dissolved in a solution of magnesia. On dialysing this solution against alcohol,
the fluid is gradually concentrated, and crystalline granules of the magnesia
compound of the protein separate out. These crystals contain 1-4 per cent.
MgO, pointing to a molecular weight of the protein of about 2800. (If X be

X 100-1-4
the molecular weight, ^q = — ^^ > therefore X = 2817.)

It is also easy to crystallise egg albumen and serum albumen. White of
egg is treated with an equal bulk of saturated solution of ammonium sulphate
to precipitate the globulins, and filtered. The filtrate is rendered slightly acid
with dilute acetic acid, which is added until a slight precipitate is formed.
The mixture is put aside for twenty-four hours, at the end of which time the
greater portion of the albumen has been precipitated as fine needle-shaped
crystals. These may be freed from ammonium sulphate by washing with a

32 PHYSIOLOGY

saturated acidified solution of sodium chloride. A similar method is used in
the case of serum-albumen. By repeated crystallisation a product may be
obtained which is absolutely constant in both its physical and chemical
characters. (Hopkins.)

The Structure of the Protein Molecule
We can only arrive at some idea of the manner in which
the protein molecule is built up, by breaking it down bit by
bit, employmg methods which will not act too forcibly in
changing the whole arrangement of the constituent parts of
the molecule. In the body almost all the protein is con-
verted into urea or carbamide (^^<Cnh!)' "^ which form it is
excreted, but we have evidence that the urea is formed by
a synthetic process from ammonium carbonate or carbamate,
which must therefore be regarded as the last stage in the
physiological dismtegration of protein. In the body many
substances are found which are presumed to be intermediate
stages in the conversion of protein into urea. Owing how-
ever to the comcidence of synthetic with disintegrative
changes in the body, it is impossible to assign these sub-
stances their exact place in the protein metabolism until we
have thrown more light on protein disintegration by chemical
experiments. In order to study this question therefore we
split up the protein molecule by simple hydrolysis. For this
purpose we may heat the protein in sealed tubes with baryta
water, or treat it with very active hydrolytic ferments, such
as the trypsin of the pancreatic juice. The most convenient
method however is to heat the protein for twenty-four
hours with a mixture of hydrochloric acid and stannous
chloride. (The use of the latter is to prevent any coincident
oxidative changes, which would tend to destroy the primary
products of hydrolysis.)

We obtain in this way an acid fluid containing an
extremely complex mixture of various substances, which may
be regarded as the proximate constituents of the protein
molecule. They may be classified as follows : —

(a) Moii-amino- acids of fatty scries. \ (6) Mon-amino-ackls of aromatic
Glycine (amino-acetic acid) | sc7-ies.

Alanine (amino-propionic acid)

Serine

Leucine (amino-caproic acid)

Aspartic acid

Tyrosine (oxyphenyl-alanin)

Phenyl-alanine

Tryptophane

Proline (pyrrolidine-carboxylic

Glutamic acid acid)

THE MATERIAL BASIS OF THE BODY

33

(c) Di-amino acids. (d) Bases,

Ornithine (di-amino-valerianic Ammonia

acid) Arginine

Lysine (di-amino-caproic acid) Histidine

(f) Sulphur-containing body.
Cystine

The amino- or amido-acids are derived from the fatty acids
by the replacement of one atom of hydrogen in the radicle
by the group amidogen, NH.,.

CH,

Thus from acetic acid I , we get amino-acetic acid or

COOH
CH,NH2

glycine | ; from propionic acid, amino-propionic acid or

COOH
CH,

I

!

alanine CH.NH,. Leucine is amino-caproic acid, and has the

COOH

formula

CH.CH,

\/

CH

I
CH,.

I
CH.NH,

COOH

^spar^ic acicZ is amino-succinic acid, C^H3(NH.,) (COOH).,,
and glutamic acid is the next higher homologue in the same
series, C3H,(NH.,) (COOH),.

In all these bodies, the acid characters of the group COOH
are almost neutralised by the presence of the basic group
NH,, so that the amino-acids as a whole are inert substances
with very feeble acid qualities. They can indeed act as bases,
giving crystalline compounds with the mineral acids.

Tyrosine is the chief aromatic amino-acid which occurs in
acid protein digests. It is formed by the coml)ination of a fatty
amino-acid with an aromatic group, being para-oxyphenyl-
amino-propionic acid

CH.,.CHNH...COOH.

/\'

OH

Both leucine and tyrosine may be prepared by evaporating
down a solution of proteins which have been acted on for

3

34 PHYSIOLOGY

twenty-four hours with pancreatic juice. When the Hquid
is allowed to cool, crystals of tyrosine separate out. These
crystals form slender needles arranged in sheaves or
radiating from a centre. The mother-liquor is evaporated
to a syrupy consistence, extracted with alcohol, and the
extract allowed to stand. As the alcohol evaporates,
yellowish-brown spheres, consisting of masses of ill-formed
needle-shaped crystals of leucine, separate out.

A solution of tyrosine with Millon's reagent gives a red
colour, the tmt of which deepens on heatmg.

When proteins are hydrolysed by means of trypsine, the
proteolytic ferment of pancreatic juice, the digest at a certain
period gives a rose colour on acidification and addition of
bromine water. This reaction is due to the presence of
another aromatic body, called tryptophane, which is a
derivative of indol, being indol amino-propionic acid.

C.CH.,.CHNH ,.COOH
C,H, CH

\ y

NH

Acted on by bacteria of putrefaction this body gives rise to
indol and skatol, substances with a pronounced faecal odour
and constantly produced in the putrefaction of proteins.

Fig. 13. Fig. 14.

Leucine ' cones ' (imperfect crystals) Tyrosine crystal? (Frey).

(Frey).

After separating all the monamino-acids, a considerable
amount of the original protein remains unaccounted for. Of
this remainder a certain amount is present in the form of the
hexone bases, so called from the fact that they all contain six

THE MATEEIAL BASIS OF THE BODY 35

atoms of carbon in their molecules. These bases can be
thrown down from the mother-liquor after the separation of
the amino-acids, or from the original acid decoction by the
addition of phosphotungstic acid. Three of these bases have
been isolated — lysine, arginine, and histidine.

Lysine has the formula CgHi^N^O.^, and is a diamino-
caproic acid, the insertion of another NH.^ group into leucine
conferring on this body strongly basic properties.

Arginine (C,;H,jN^02) was first prepared from the seedlings

of certain plants. Its chief interest lies in the fact that on

boiling with baryta water it is split up, giving as one of its

decomposition -products urea. We thus see that a certain

proportion (not more than one-ninth) of the urea which is

excreted by the body may be derived by a process of simple

disintegration of the proteins of the food, without any

accompanying oxidation. Arginine belongs to the same class

of bodies as creatine — an important constituent of all muscular

tissues. Creatine or methyl-guanidin-acetic acid has the

formula

NHx ;

^C -N(CH3).CH.,C00H.
NH,/ j

On boiling creatine with baryta water, it takes up a molecule
of water and splits into two halves in the situation of the
dotted line in the formula, giving

NH,v

>C0 (urea) and NH(CH3)CH,C00H.
NH/

This latter substance is known as sarcosine, and is derived
from glycine by the replacement of one atom of hydrogen by
a methyl group, CH3.

Arginine has a similar formula. On the left-hand side of
the dotted line the formula would be identical with that of
creatine. On the right-hand side however, the sarcosine
group is replaced by a diamino-acid of the fatty series,
diamino-valerianic acid or ornithin.

Histidine has the formula CgHgNgO.^. It contains the
alanine group, being imidazol amino-propionic acid. It does
not yield urea on boiling with baryta water.

Nearly the whole of the sulphur in the protein mole-
cule exists or can be separated in the form of cystine. This

36

PHYSIOLOGY

substance is a crystalline solid, which under some con-
ditions may occur in considerable quantities in the urine
(cystinuria), and in such cases may give rise to a urinary
calculus. It can be regarded as a sulphur derivative of
lactic acid CH3.CHOH.COOH, or of amino- propionic acid
CHg.CHNH^.COOH, and has the formula

CH.,— S— S-CH..

CH.NH..

COOH

CH.NH,

COOH.

Other amino-acids and allied substances, besides those
mentioned, occur in various tissues and fluids of the body.
Since however they do not lie on the direct line of protein
katabolism, M'e shall consider their chemical properties in
connection with the organs in which they occur.

A comparison of the relative amounts of these substances to be obtained
by the decomposition of different proteins shows marked variations, pointing
to fundamental differences in their constitution. This is well seen in the
following table, in which is given the relative i^roportions of the more important
decomposition products : —

Casein (of milk)

Globiii (from lisemo-

Edestin (a vegetable pro-

gloDin)

tein from hemp-seeds)

Glycine

0

0

3-8

Alanine

0-9

4-2

3-6

Leucine

10-5

290

20-9

Glutamic acid

10-7

1-7

6-3

Aspartic acid

1-2

4-4

4-5

Tyrosine

4-5

1-3

21

Phenylalanine

3-2

4-2

2-4

Proline .

31

2-3

1-7

Lysine .

5-8

4-2

20

Arginine

4-8

5-4

11-7

Histidine

2-6

10-9

10

Cystine

006

0-3

0-25

Tryptophane

1-5

present

present

A class of bodies known as protamines occurs in the heads of spermatozoa
of salmon and some other fishes in combination with nucleic acid. The
protamines react in many ways like proteins, giving the biuret^ reaction.
When they are hydrolysed by strong hydrochloric acid, they give off nearly
all their nitrogen in the form of the ' hexone bases,' arginine, lysine, and
histidine. They give also small amounts of monamino-acids. It has been
suggested by Kossel that the typical protein molecule may be regarded as a
nucleus composed from the hexone bases, to which is tacked on a number
of monamino-acid groups, the relative proportion of the bases in the nucleus,
as well as of the subsidiary amino-acids, differing according to the nature
of the protein in question. According to this view, the protamines would
lepresent the simplest type of protein.

THE MATERIAL BASIS OF THE BODY 37

Most nuclei, including the spermatozoa of most animals, contain another
class of bodies, called liistones, in combination with the nucleic acid. Histones
give the ordinary protein reactions, their chief characteristic being the fact
that they are precipitated by ammonia. Their disintegration products are
such as would be obtained from a mixture or combination of ordinary protein
with a protamine. Thus, roughly speaking, on hydrolysis by means of acids,
the ordinary proteins of our food and tissues give about 10 per cent, of hexone
bases, histones about 20 to 25 per cent., while protamines yield about 90 per
cent, of lysine, arginine, and histidine.

Polypeptides. — E. Fischer has succeeded in uniting two or
more molecules of various amino-acids to form large molecules
which give the biuret reaction, and might be regarded as
elementary proteins or parts of proteins. Some of these
bodies may be hydrolysed by trypsine (the proteolytic ferment
of pancreatic juice) into their constituent amino-acids. To
these synthesised substances Fischer has given the name
polypeptide. Examples of such bodies are glycyl-glycine,
leucyl-tyrosine, glycyl-leucyl-tyrosine.

A similar body — namely, glycyl-alanine — has been obtained
directly by the hydrolysis of silk, which suggests that these
combinations actually occur as part of the constituent frame-
work of proteins. As a type of the manner in which these
substances are built up, we may give the formula of glycyl-
glycine : —

H-N-CH.,CO.OH

I

CO - CH,.NH,.

General Tests for Proteins

1. On boiling proteins in a very slightly acid solution,
they are coagulated, and form an insoluble white precipitate.

The best method of carrying out this test is to boil the solution in neutral
or slightly alkaline solution, and then while in active ebullition to drop in
dilute (1 or 2 per cent.) acetic acid until the reaction is slightly acid. If the
solution is poor in salts, 1 or 2 per cent, of NaCl should be added at the com-
mencement. By this means a nearly perfect separation of all the coagulable
proteins may be effected.

2. On pouring a solution of protein carefully down the
side of a test-tube containing strong nitric acid, so as to form
a layer on the top, a white layer of coagulated protein is pro-
duced at the junction of the two fluids.

3. Acetic acid and potassium ferrocyanide give a white
precipitate.

38 PHYSIOLOGY

4. Saturation of protein solutions with annnonium sul-
phate causes complete precipitation of all proteuis present.

5. All coagulahle proteins are completely precipitated by
adding to their solutions an equal bulk of 10 per cent, tri-
chloracetic acid, or of a 5 per cent, solution of metaphosphoric
or of salicyl-sulphonic acid.

6. All proteins are precipitated and coagulated by the
addition of solutions of picric acid, mercuric chloride, copper
sulphate, tannic acid, or of strong alcohol.

7. Excess of caustic potash or soda with a drop of dilute
copper sulphate gives a violet colour (Piotrowski's reaction).

8. On adding strong nitric acid to a protein solution and
boiling, a yellow colour is produced which turns to deep
orange when ammonia is added (xanthoproteic reaction).

9. Millon's reaction. An acid solution of nitrate of
mercury gives a white precipitate which turns a brick-red
on boiling.

10. On addmg some weak glyoxylic acid (prepared by the
action of sodium amalgam on oxalic acid) to a protein solution
and then some strong sulphuric acid, a deep red-purple colora-
tion is produced (Adamkiewicz-Hopkins reaction).

Meaning of the Protein Tests. — The last four of these tests are of interest
as throwing some hght on _the constituent parts of the protein molecule.
Thus Piotrowski's reaction (often called the biuret reaction) depends on the

CH,-NH,
presence in the protein molecule of groups having the formula | ,

CO-NH
and is given by a number of substances in which two CO.NHo or CH._>.NH.>
groups are coupled together either directly, or by a NH or CH. group. Since
the terminal NH„ group is destroyed by nitrous acid, this acid at once destroys
the power of proteins to give the biuret reaction.

The xanthoproteic reaction depends on the presence in the protein
molecule of an aromatic group with the benzene-nucleus: —

H

c c

hI^ %

V

Millon's reaction depends on the presence of a hydroxy-derivative of
benzene, and is mainly conditioned in the protein by the tyrosine group, a
compound of hydroxyphenyl with alanine (amino-propionic acid).

The Hopkins-Adamkiewicz reaction is determined by the tryptophane
group in the protein molecule.

THE MATERIAL BASIS OF THE BODY 39

Classification of Peoteins

The only satisfactory classification of proteins would be
one founded on an exact study of their disintegration products.
Since however we do not know all these products in the case
of even a single protein, it is obviously impossible to attempt
any classification on such a basis, and we have therefore to
make use temporarily of a purely artificial classification based
on the solubilities of the various proteins in water and salt
solutions. The fact that simple mechanical shaking may
convert a globulin into a coagulated protein will serve to
illustrate how entirely artificial is our present mode of classi-
fication. Adopting the solubilities as a basis, we may divide
the proteins into the following classes :

1. Native Albumens. — These are soluble in pare water and
are precipitated by saturation with sodio-magnesium sulphate
or with ammonium sulphate.

Egg albumen forms the greater part of the white of egg.
It gives the ordinary protein tests, and is precipitated if
shaken up with a drop of dilute sulphuric acid and excess of
ether. It rotates the plane of polarised light to the left 35-5°.
If injected into the circulation it gives rise to albuminuria and
is partially excreted by the kidneys.'

Serum albumen occurs m large quantities in the blood-
plasma and serum, and m small quantities in most tissues of
the body. It coagulates at 75° C, and is distmguished from
egg albumen by its greater specific rotatory power (56°), and
by the fact that it is not precipitated by ether and sulphuric
acid, and if mjected into the circulation does not reappear in
the urine.

2. Globulins. — These bodies are insoluble in pure water
and require a certain amount of neutral salt present to dis-
solve them. They are the most mterestmg of all protein
groups, playing an important part in nearly all vital processes.

' This statement has given rise to the idea that the cells of the kidney are
permeable to egg albumen but not to serum albumen. This idea is not
warranted. The fact is that egg albumen is, or contains an ingredient which
is, poisonous and injures the kidney cells. These therefore become permeable
to proteins, and albuminuria results. But the proteins of the urine are those
which normally occur in albuminuria, viz. serum albumen and serum globulin,
containing however a certain amount of tlie foreign protein circulating in the
blood, namely egg albumen.

40 THYSIOLOGY

But it must be remembered that we are not justified in speak-
ing of the globulins whicli we extract from the tissues and
treat by precipitation and washing till they are no longer
altered by these processes, as the active agents in the com-
plex protein interactions which make up the sum of vital
phenomena. Our purified protein is a wreck, and represents
merely the framework on which the living protoplasmic
molecule was built up.

All the globulins are precipitated from their solutions by
saturation with magnesium sulphate and partially by satura-
tion with sodium chloride. The chief members of this class
are —

Crystallin, ol)tained from the crystalline lens by passing
a stream of CO^ through an aqueous extract of this body.

Paraglohulin.

Fibrinogen.

Myosin or 2)ciramyosinogeii.

These three bodies will be considered in the chapters on
blood and muscle.

3, Derived Albumens. — These may be regarded as compounds
of proteins with acids or alkalies.

Acid albumen is formed by the action of warm dilute
acids or by strong acids in the cold on any of the preceding
bodies. If an alkaline solution be added so as to nearly
neutralise the solution of acid albumen, this latter is precipi-
tated. If the precipitate be suspended in water and heated, it
is coagulated and becomes insoluble in dilute acids or alkalies.

Alkali alhuineoi is formed by the action of strong caustic
potash on white of egg or on any other protein, or by adding
alkali in excess to a solution of acid albumen. It is pre-
cipitated on neutralisation of its solution.

In close association with this group may be included the proteins as they
occur in combination with the metallic salts, such as copper sulphate. On
splitting off the copper moiety from these compounds, the protein left is
practically free from ash, and behaves in many respects like an albuminate,
being insoluble in absolutely pure water, but easily dissolved by the addition of
a trace of free acid or alkali.

An inoeresiing group of protein derivatives has been described by Hopkins,
produced by the action of the free halogens on protein solutions. We get
in this way two definite classes of compounds. One class, which contains
the largest iiercentage of halogens, is obtained by treating a protein solution
with chlorine, bromine, or iodine, dissolving up the resultant precipitate in
alcohol and pouring the alcoholic solution into ether, when the halogen

THE MATERIAL BASIS OF THE BODY 41

compound is thrown down as a fine wliite precipitate. By dissolving up this
precipitate in weak soda and precipitating with acid, we obtain a series of com-
pounds containing only about one-third as much of the halogen as is contained
in the first precipitate, suggesting that the halogen forms both substitution
and additive compounds with the protein molecule.

4. Fibrins. — The chief of these is blood-fibrin, a .stringy
protein formed in the clotting of the blood and giving
solidity to the clot. It is insoluble in water and salt solutions.
In dilute hydrochloric acid it swells up, and if kept at 40^ C.
it dissolves with the formation of acid albumen. If suspended
in water and heated it is coagulated, and is no longer capable
of swelling up in dilute hydrochloric acid. Similar bodies,
myosin- and myogen-fibrin, are formed in the coagulation or
rigor of voluntary muscle.

5. Coagulated Proteins. — Any member of the preceding
classes, when heated in a neutral or slightly acid solution,
is converted into coagulated protein. In this condition it
is insoluble in water, saline solutions, or weak acids. It is
dissolved by strong acids or alkalies or by the digestiv
ferments such as the gastric and pancreatic juices.

Hydrated Proteins

When proteins are subjected to the action of superheated
water or steam, or are heated with acids, or acted on at the
body temperature by certain ferments (trypsine or papain),
they undergo a change which is supposed to be attended
with the addition of one or more molecules of water to the
protein molecule (hydrolysis). The final result of this action
is the group of nitrogenous bodies, chiefly belonging to the
amino-acids, which we have already dealt with. As inter-
mediate products in this series of hydrolytic changes, we find
a group of bodies, still presenting many of the protein re-
actions, which are classed as hydrated proteins, and include
the proteoses or albumoses and the peptones.

1. Albumoses. — These are all precipitated from their solu-
tions by saturation with ammonium sulphate. On addition
of nitric acid they give a precipitate in the cold, which is
dissolved on heating but reappears on cooling. On adding
an excess of caustic potash and a drop of verij dilute copper
sulphate to a solution of albumoses, a pink colour is pro-
duced (biuret reaction). If more copper sulphate be added,

42 PHYSIOLOGY

the pink colour is changed to violet similar to that produced
in a solution of proteins.

According to their solubilities three varieties of albumoses
may be distinguished :

a. Proto-albumoses. Soluble in pure water; precipitated
by saturation with sodium chloride or ammonium sulphate.
With acetic acid and potassium ferrocyanide it gives a white
precipitate.

b. Hetero-alhumose. — Insoluble in pure water ; soluble in
weak saline solutions or dilute acids ; precipitated by satura-
tion with salt, or by acetic acid and potassium ferrocyanide.

c. Deutero-albmnoses. — Soluble in pure water ; not pre-
cipitated by saturation with common salt, except after addi-
tion of a little strong acetic acid ; entirely precipitated by
saturation with ammonium sulphate. They give no precipitate
with acetic acid and potassium ferrocyanide.

2. Peptones. — Soluble in pure water ; diffusible through
animal membranes ; with caustic potash and copper sulphate
they give the same reaction as albumoses. From the latter
class peptones are distinguished by the fact that they are
not precipitated at all by saturation with ammonium sulphate
or with any neutral salt.

Albumoses and peptones give the xanthoproteic and
Millon's reactions common to all proteins ; and like these
are precipitated by tannic acid, mercuric chloride, and
potassio-mercuric iodide.

Conjugated Proteins

This name may be applied to various complicated bodies,
which resemble one another only in the fact that in each of
them a protein radical is combined with some other body.

1. Haemoglobin, the red colouring matter of the blood, is
readily crystallisable. On boiling an aqueous solution it
splits up into coagulated protein (globin) and an iron -contain-
ing body named haematin (Cy.^Hg^N^O^Fe). Its properties will
be described in the chapters on blood and respiration.

2. Nucleo-proteins. — These are a group of bodies occur-
ring in large quantities in the protoplasm of cells. They
are also found in the chyle, in lymph, and in blood-plasma.
They consist of protein combined with a nitrogenous body

THE MATERIAL BASIS OF THE BODY 43

rich ill phosphorus called iiuclein. As they occur in the
cells, they are in most cases soluble in water or in salt
solutions, but after separation they need the presence of
free alkali for their solution. When subjected to gastric
digestion, they are split up, the protein half being converted
into albumoses and peptones, while the nuclein is pre-
cipitated. The nuclein thus obtained is a white amorphous
powder, insoluble in water, salt solutions, or acids, but soluble
in strong alkalies. It forms the chief constituent of cell
nuclei, and consists of a combination of protein, or pro-
tamine, or histone, with a complex body containing nitrogen
and phosphorus known as nucleic acid.

When the latter is heated with strong acids, it breaks up
into phosphoric acid and a number of other substances,
amongst which the most important are bases allied to uric
acid and belonging to the xanthin or purin series (xanthin,
hyj)oxanthin, adenin).

In many cases a carbohydrate is found among the
products of disintegration of nuclein. As first extracted
from the animal cell, the nucleo-proteins are associated
with a considerable proportion of lecithin, and in this fresh
labile condition form the tissue-librinogens of Wooldridge.
To prepare these substances, an organ rich in cells such as
the thymus is minced and extracted with water or normal salt
solution. After separating the cells by means of the centri-
fugal machine, the clear fluid is decanted off and acidified
with acetic acid. A precipitate is produced, consisting of
tissue-fibrinogen. This substance is soluble in excess of acid
and is easily soluble in alkalies. All the tissue-fibrinogens
are highly unstable bodies and undergo changes m the mere
act of precipitation and resolution. When injected mto the
blood, they cause intravascular clotting. On digestion with
gastric juice, they yield a precipitate of nuclein, and this
precipitate contains a large proportion of the lecithin present
in the original substance.

These complex bodies form the greater part of the proto-
plasm of a living cell. The chromatic part of the nuclei
appears to be formed in most cases of nuclein, but the purest
nuclear material at our disposal, the heads of spermatozoa,
is found to consist almost entirely of a definite compound of
nucleic acid and either protamines or histones, so that the

44

PHYSIOLOGY

essential chemical constituents of a living cell are here reduced
to their simplest possible expression.

The chemical relationships of the iiucleo-proteins may be
rendered clearer by tlie following table.

Cell protoplasm
(extracted, treated with acetic acid).

NxwJeo-protein (precipitate)
(on digestion).

Histone, etc. (in solution)

Nuclein (precipitate)

(dissolved in strong alkali, and precipitated with HCl).

Peptone (in solution).

Nucleic acid (precipitate)
(heated in sealed tube with HCI).

Acid albumen (in solution)
or Protamine.

Pliosphoric odd. Purine bases. Rediicing stigar ? Pyrimidine bases and

Xanthine, CjH^N.iO.^. other less known sub-

Hypoxanthine, C^HiNiO. stances.
Adenine, C-H^N,.

TJie caseinogen of milk is often grouped with the nucleo-
proteins, since like them it gives a phosphorus-containing
precipitate on digestion with gastric juice. Like them too
it is precipitated by the addition of excess of acid and is
soluble in alkalies. The precijDitate however which is yielded
by gastric digestion is not a true nuclein, since it does not
give the xanthin or purin bases on heating with hydrochloric
acid. It seems in fact to be little more than an insoluble
compound of phosphoric acid with protein, and has been
termed pseudo-nuclein or paranuclein. The precipitate is
stated to be absent in the case of caseinogen of human milk.
With rennet ferment caseinogen undergoes coagulation, form-
ing casein or cheese (y. Chap. VIII.). Caseinogen, with certain
other proteins presenting similar properties, are often put in
a distinct class as the phospho-proteins.

THE MATERIAL BASIS OF THE BODY 45

3. Glyco-proteins. — This class of bodies is of considerable
interest, since in many cases its members may represent
stages in the upbuilding of carbohydrates in the protoplasmic
molecule. They have been regarded as glucosides of the
proteins, but in all cases where the carbohydrate moiety has
been isolated in a state approaching purity, it has been
found to contain nitrogen. Probably therefore in most in-
stances the conjugation is not between glucose and protein,
but between a body of the composition of glucosamme and
protein.

Glucosamine was first procured by boiling the chitinous
shells of Crustacea with hydrochloric acid. It is formed from
a molecule of grape-sugar or other liexose by the replacement
of an OH group by NH^. In chitin this substance occurs in
combination with acetic acid or some derivative of acetic acid.
A somewhat similar substance is found in the cartilage of
vertebrates. The cartilage matrix contains two chief sub-
stances, chondro-mucoid and chondrin. By long extraction
with weak alkali, a paired acid, chondroitin-suljjhuric acid,
can be extracted from both these bodies, leaving behind in
the case of chondro-mucoid a substance of the protein class,
in the case of chondrin pure gelatin. On boiling the chon-
droitin- sulphuric acid with weak acid it is decomposed, with
the formation of a body, chondrosin, which reduces Fehling's
solution and appears to be compounded of two derivatives
of glucose, viz. glycuronic acid (C,.H|,|0-) and glucosamine
(C,H„0,.NH,).

It is possible that many so-called simple proteins contain
a small amomit of a carbohj^drate residue wrapped up in their
molecule. Thus from egg albumen, even crystallised, it is easy
to prepare a reducing substance which gives a definite osazone.
We have seen moreover that a carbohydrate may occur in
the decomposition of nucleic acid. In the typical glyco-pro-
teins however, the carbohydrate moiety forms a much greater
part of the molecule than in the last two cases. They may
be classified as follows.

1. Mucins. Mucin occurs in the saliva, and as a product
of secretion of the mucous glands throughout the alimentary
tract, and as a skin-secretion in many lower animals. It also
forms an important constituent of the ground substance of
connective tissue, from which it may be extracted by treat-

46 PHYSIOLOCtY

ment with lime or baryta water. On boiling with dilute
mineral acids, it is converted into an acid-albumen and a
reducing substance containing nitrogen which appears to be
isomeric with glucosamine, and has been called mucosamine.
Owing to its content of protein it of course gives the ordinary
protein tests. It swells up in water, forming a viscid slimy
mass. It is precipitated by acetic acid, and is insoluble in
excess of this reagent. It is soluble in dilute alkalies.

2. The mucoids include a number of substances, such as
colloid, ovo-mucoid, pseudo-mucin, which are obtained from
ovarian cysts and other pathological formations. They also
appear to be glucoside-like combinations of a protein with
some body allied to glucosamine, or the anhydride of such
a body.

3. The chondro-proteiiis include substances which are
compounded of chondroitin-sulphuric acid and protein. One
example of this class we have already mentioned mider the
name of chondro-mucoid. Another important substance is
the amyloid substance or lardacein which is found in the
middle coats of the blood-vessels, in the liver, and other organs
under certain pathological conditions. It is insoluble in
water, alkalies, acids, or gastric juice. It gives a red-brown
colour with iodine, which, on the addition of strong sulphuric
acid, turns to a dirty-blue colour.

Bodies allied to Proteins, or Albuminoids

Under this heading we may group a number of diverse
bodies.

1. Gelatin may be extracted from all connective tissues,
especially bone and white fibrous tissue, by prolonged boiling
with water. It forms a solution in water, which is liquid at
high temperatures but sets into a jelly when cold. It is pre-
cipitated by tannic acid, but not by acetic acid. No tyrosine
can be formed from it by boiling with dilute sulphuric acid, and
on this account pure gelatin does not give a red colour when
boiled with Millon's reagent. Gelatin is not present as such
in the tissues, but is formed from a precursor {collagen) by
prolonged boiling with water.

2. Ghondrin may be extracted by boiling cartilage. Its
solutions are precipitated by acetic acid, and form a jelly
when cold. On boiling with dilute acids it is split up, with

THE MATERIAL BASIS OF THE BODY 47

the formation of a body possessing the power of reducing
Fehling's solution. It has been shown that chondrin is a
compound of gelatin with a sulpho-acid (chondroitin- sulphuric
acid, q.v., p. 45).

3. Elastin, the substance of which the yellow fibres of
connective tissue are composed, is insoluble in water and dilute
acids or alkalies. It is very slowly dissolved by gastric
juice.

4. Keratin forms the main part of the horny layer of the
skin, nails, hair, hoofs, etc. It is very insoluble. It presents
the same elementary composition as the proteins, but is
distinguished from them by the very large quantity of sulphur
present, which may amount to 5 per cent. A very similar
substance, neuro-keratin, can be obtained from the supporting
framework (neuroglia) of nervous tissues.

Both elastin and keratin give the colour-reactions of pro-
teins, especially the xanthoproteic and Millon's reactions.

48

PHYSIOLOGY

Section 3
THE PATS

These bodies consist of the elements carbon, hydrogen,
and oxygen. They occur to some extent in most tissues and
form the greater part of adipose tissue.

The lower acids of the fatty series are represented by
formic, acetic, propionic, butyric acid, etc., and have the
general formula C„H^„0.j. The following formuhe will serve
to show the manner in which they are built up :

>rmic acid.

H

1

Acetic acid.
CH3

rroploiiic acid.

CH3

1

Butyric

CH,

1

acid.

Valerianic acid.
CH3

1

Caproic acid
(normal).

CH3

1

COOH

COOH

i
CH..

1

1
CH,.

1

CH,

1
CH,

1

COOH

1
CH,,

1

CH.,

1

1
CH,

I

COOH

1
CH.,

1

CH,

1

COOH

1
CH..

i
COOH

Thus by adding the group CH^ a whole series of bodies
can be formed increasing in molecular weight. The 16-carbon
acid is palmitic acid, and the 18-carbon acid is known as
stearic acid.

Besides these we have another group of the general
formula C,^.^,,^^^.., in which two of the CH, groups are
replaced by two CH groups linked by double bonds, thus

II . To this group belongs the other chief acid of the fats,

CH

viz. oleic acid, CjgHg^O.^.

The fat of adipose tissue consists of a mixture of olein,
palmitin, and stearin, the first being liquid and the two latter
solid at ordinary temperatures.

Fats may be considered as compomids of the triatomic
alcohol, glycerin (C3H^^(OH)3), with oleic, stearic, or pal-
mitic acid, water being eliminated in the act of combination.
Thus :

C3H,(OH)3 + 8(C.,H330.0H) = C3H,(O.C,,H330), + 3H.,0.

Glycerin. Oleic acid. Olein, Water.

THE MATERIAL BASIS OF THE BODY 49

Fats are insoluble in water, but soluble in ether and in
hot alcohol. When boiled with alkaline solutions, they are
split up with the formation of glycerin and a compound of
the fatty acid with the alkali, which is called a soap. The
alkaline soaps are soluble in water.

In the fats of milk (butter) we hnd lower acids of the
fatty series, such as butyric, caijrylic, and caproic acids,
combined with glycerin. Acetic acid is also a member of the
fatty acid series. It occurs in the body as an amino-acid,
glycine.

Lecithin. — This substance is a wax-like body which is
universally distributed in the organism, and is found in espe-
cially large quantities in the white matter of nerves and of
the spinal cord. It may be regarded as a compound of a
molecule of glycerin with two of stearic acid, one of phos-
phoric acid, and a molecule of a nitrogenous base, cholin. Its
composition is represented by the following formula :

((C.sH3,0,).

[^ ^"^ (0-aH,— N(CH3)30H.

Lecithin is miscible in all proportions in ether, alcohol,
and fats. It swells up in water, of which it can imbibe a
large quantity.

Cholesterin may be considered here although it does not
belong to the group of fats. Like lecithin it is found wherever
protoplasm is present and seems to be an essential con-

Fiu. l.j.

Cholesterin crystals.

stituent of every living cell. It is a monatomic alcohol
(C2,;H,3.0H). It is easily soluble in ether or hot alcohol.
From the latter it is deposited on cooling in typical plate-like

4

50 PHYSIOLOGY

crystals, each of which has a corner knocked out. It is
insohible in water but sHghtly sohible in a sokition of bile-
salts. Its history and use in the body are absolutely un-
known.

Tests for cholesterin.~{\) On dissolving cholesterin in chlorofoi-ni and then
adding an equal volume of concentrated sulphuric acid, the cholesterin solution
becomes first blood-red and then a more violet-red, while the sulphuric acid
appears dark red with green fluorescence.

(2) On moistening cholesterin crystals with sulphuric acid diluted with one-
fifth of its bulk of water, the edges of the crystals become reddish and then
violet. If a little iodine solution be now added, the crystals become by degrees
violet, bluish-green, and then blue.

THE MATEEIAL BASIS OF THE BODY 51

Section 4
THE CAEBOHYDEATES

These substances occur in large quantities in plants, and
therefore are important constituents of the food. Only
small amounts of carbohydrates however are at any given
time present in the body, where they may occur as sugar or
animal starch, or built up with proteins and allied bodies
into more complex compounds. They all consist of carbon,
hydrogen, and oxygen, both the latter substances being
present in the same proportions as they exist in water. Their
general formula is therefore C^H.^^O,,. They may be divided
into three classes : mono- saccharides, di- saccharides, and
poly-saccharides.

1. The Mono-saccharides

These bodies are all ketone or aldehyde derivatives of
polyatomic alcohols. Thus from alcohols of the formula
CgH,^Og may be derived by oxidation either the aldehyde,
d-glucose or grape-sugar, CH.,OH(CHOH)^COH, or the ketone,
d-fructose or Ifevulose, CH,0H(CH0H)3C0.CH,0H.

The sugars (of which grape-sugar is a type) containing the aldehyde group
— COH, are spoken of as aldoses. Those wlrich, like Itevulose, contain the
ketone group — CO — are called kctoses.

The di- and poly-saccharides are derived from the mono-
saccharides by a process of condensation attended with the
elimination of water. The mono- as well as the di-saccharides
are all distinguished by names ending in — ose. Thus
according to the number of carbon atoms present, we may
distinguish trioses, tetroses, pentoses, hexoses, etc. Of the
sugars only those with six carbon atoms, viz. the hexoses,
which are of physiological importance, need concern us here.

All the sugars resemble the ordinary aldehydes in being
possessed of strongly reducing properties. Thus they reduce
cupric to cuprous hydrate on boiling, and ammoniacal solu-
tions of silver to the metallic condition. From a practical
standpoint one of their most important reactions is that with

52 PHYSIOLOGY

phenylhydrazine. On boiling an aqueous solution of sugar
with phenylhydrazine and acetic acid, two sets of bodies are
formed, first hydrazones and then osazones. The reaction
which goes on is represented by the following equations :

CH20H(CHOH)3CHOH.CHO + H2N.NH.C,H5 =

Glucose. Phenylhydrazine.

CH,0H(CH0H)3CH0H.CH : N.NH.C.H. + H^O.

Phenylglucosehydrazone.

The hydrazone then reacts with another molecule of
phenylhydrazine to produce an osazone.

CH20H(CHOH)3CHOHCH : N.NH.C,H, + H2N.NH.C,H,=
CH,0H(CH0H)3C.CH : N.NH.C.H,

II +H2O + H,.

N.NH.CfiHs

The hydrogen however is not given off in the free state
but acts on a third molecule of phenylhydrazine, splitting it
into aniline (C,.Hg NH2) and ammonia.

The osazones are yellow crystalline compounds, which
have definite solubilities and melting-points, varying accord-
ing to the sugars from which they have been derived. Hence
these compounds are of great value in the separation and
identification of sugars in a complex mixture. By acting on
the osazones with reducing agents, such as zinc and acetic
acid, an osamine is formed, e.g. glucosamine, and from this
a sugar can be re-obtained by the action of nitrous acid. In
this case however the sugar is always a ketose, so that we
may in this way convert glucose into fructose or laevulose.

A very large number of hexoses are known, the differ-
ences depending partly on the variations in the structural
formula, partly on the varying position of the constituent
atoms of the molecule. Owing to the asymmetric structure
of the molecules, there are three sugars corresponding
to each structural formula. Two of these are optically
active and rotate the plane of polarised light either to the
right or to the left, while a third modification is inactive
and can be regarded as consisting of an equal number
of molecules of the two active varieties. It is customary
to classify the glucoses into d- (dextro-rotatory), 1- (laevo-

THE MATEKIAL BASIS OF THE BODY 53

rotatory), and i- (inactive) groups, and to distinguish the other
sugars by the letters of the ghicose with which they are
most nearly connected, without any reference to their optical
characters. Thus fructose or laevulose, although it is la3vo-
rotatory, is distinguished as d-fructose owing to its relation-
ships with grape-sugar, d-glucose.

The different varieties of sugars are however easily con-
vertible one into the other. Thus by the action of weak
alkalies, glucose is converted into fructose and mannose and
two other sugars.

A number of the mono- saccharides are acted upon by yeast
with the formation of alcohol, CO2 being evolved in the pro-
cess. This action however is confined to the mono-saccha-
rides with three, six, or nine carbon atoms. Moreover
certain of the artificially prepared hexoses, as well as some
occurring m combination with proteins in the glyco-proteins,
are insusceptible to the action of yeast.

Of the numerous hexoses known, we Dieed only describe
three which are of physiological importance, i.e. grape-sugar,
galactose, and fructose or Itevulose, the two first being aldoses
while the latter is a ketose.

Gra])e-siigar (d-glucose) or dextrose is found in small
quantities in the blood and in numerous tissues of the body,
and is the form to which all carbohydrates are converted
before they reach the circulation. It occurs m large quanti-
ties in grapes and, mixed with hievulose, m honey and various
fruits. When pure it forms colourless crystals which are
easily soluble in water. Its solutions rotate the plane of
polarised light to the right.

Tests for dextrose. — 1. Moore's test. On warming a solu-
tion of dextrose with caustic potash or soda, the solution
turns first yellow and then brown.

2. Trommer's test. On adding caustic potash or soda to
a solution of dextrose and then a few drops of copper sul-
phate, the cupric hydrate produced is dissolved to form a
deep-blue fluid solution. On heating to boiling, the cupric
is reduced to cuprous hydrate, which is thrown down as
a yellow or red precipitate. Fehlmg's reaction is merely
a modification of this test. An alkaline solution of cupric
hydrate is prepared by adding Eochelle salt and potash to
a solution of copper sulphate, the tartrate serving to keep

54 PHYSIOLOGY

the cupric hydrate in yolution. On boihng some of this
' FehHng's sohition ' with dextrose, it is reduced with the
production of the red cuprous hydrate. The proportions of
the ingredients are so adjusted that 1 c.c. of FehHng's solu-
tion is exactly reduced by 0-005 gramme dextrose.

3. The phenylhydrazme test for sugar has already been
described. The phenylglucosazone forms masses of yellow
]ieedle-shaped crystals which, when purified by recrystallisa-
tion from alcohol, melt at 204° C.

Lixvulose, fruit-sugar or d-fructose, occurs in fruits and
honey in association with dextrose. It is also produced by
the hydrolysis of a species of starch called inulin, and
together with dextrose by the inversion of cane-sugar. It
gives the same tests as dextrose, but rotates the plane of
polarised light to the left.

Galactose is obtained together with dextrose by the inver-
sion of milk-sugar, and is also present in the glucoside,
cerebrin, which is found in the brain. It rotates the plane
of polarised light to the right.

2. The Di-saccharides

The di-saccharides can be regarded as anhydrides formed
by the combination of two mono-saccharides with the elimina-
tion of one molecule of water. Hence their general formula
is Ci2H220,i. Under the action of hydrolytic agents they
take up a molecule of water and split into two molecules of
hexobe. Thus

Cane-sugar + H^O = dextrose -1- laevulose.
Lactose -I- H20 = dextrose + galactose.
Maltose + H^O = dextrose + dextrose.

Cane-sugar is the most important member of this group,
and takes a prominent place in our dietary. It is crystalline
and easily soluble in water. On boiling with dilute mineral
acids or under the action of certain ferments, it undergoes
inversion, taking up one molecule of water and splitting into
dextrose and Itevulose.

C^H^^O^ -f H,0 = C,3H. A + CeHi A-

Cane-sugar. Dextrose. Lasvulose.

THE MATERIAL BASIS OF THE BODY 55

Under the action of the yeast fungus, cane-sugar is first
inverted, and the invert-sugar is then converted into alcohol
with the ebullition of CO.^.

C,H,A = 2C2H,0-f2CO,.

Alcohol.

Cane-sugar does not reduce alkaline solutions of cupric
hydrate such as Fehling's solution. When warmed with
sulphuric acid it turns black. On addmg concentrated
hydrochloric acid to a strong solution of cane-sugar and
heating, the fluid turns a deep-red colour. The same reac-
tion is given by Isevulose, but not by dextrose.

Lactose or milk-sugar occurs in milk. It is much less
soluble in water than cane-sugar and is only faintly sweet.
It reduces Fehling's solution. On boiling with dilute acids
it takes up water and is converted into dextrose and the
isomeric sugar known as galactose.

C,,H,,0„ 4- H,0 = C.H. A + C,3H,,0,.

Lactose. Galactose. Dextrose.

With the lactic acid organism it is converted into lactic acid.
To this conversion of lactose into lactic acid is due the sour-
ing of milk.

C„H,,>0^,-i-H.,0 = 4C3HA-

Lactose. Lactic acid.

Maltose is the end-product of the action of diastase,
salivary or pancreatic ferments on starch. It reduces
Fehling's solution and is converted on boiling with dilute
mineral acids into dextrose.

3. The Poly-saccharides

This group includes a large number of highly complex
bodies which all occur in the amorphous condition and
belong to the class of colloids. Their general formula is
(CyH,||0^)x, where x may be anything from twenty up to a
hundred or more. By hydrolysis they are all converted
finally into mono-saccharides. They may be divided into
three groups, starches, dextrins and gums, and celluloses ;
but we need concern ourselves here only with those members
which are of physiological importance.

Starch does not occur in the living body, but constitutes
an important foodstuff, being present in large quantities in

56 PHYSIOLOGY

nearly all vegetable food. It is a white powder consisting
of microscopic grains with concentric rings. It is insoluble
in cold water. When boiled with water, it swells up to form
an opalescent semi-solution. This solution gives an intense
blue colour with iodine. On boiling with dilute acids, starch
is converted first into dextrin and then into dextrose. With
various ferments, such as diastase (malt ferment), salivary
or j)ancreatic ferments, it undergoes hydrolysis and is con-
verted into dextrin and maltose. The change that occurs on
boiling with acids may be thus represented :

C,H„0, + H,0 = C,H,,0,.

starch. Water. Dextrose.

Glycogen or animal starch is found in the liver, muscles,
and other tissues of the body, and occurs in especially large
quantities in all fcetal tissues. It is a white powder soluble
in cold water, forming an opalescent solution. With iodine
it gives a mahogany-red colour. It is affected by acids and
ferments in the same way as starch. It is precipitated from
its solution on the addition of alcohol to 60 per cent. It
is moreover precipitated by saturation of its solutions with
ammonium sulphate.

Dextrin. Two varieties of this body may be distinguished
according to their reaction with iodine — erytJtrodextrin which
gives a red colour with iodine ; and achroo dextrin which
gives no colour.

It is said to occur m small quantities in blood, muscle,
and liver, but it is chiefly of importance as being an inter-
mediate product in the digestion of starch. It is gummy and
amorphous, readily soluble in water but insoluble in alcohol
and ether. On boiling with acids it is converted into dex-
trose. It is not thrown do^vn on saturation with ammonium
sulphate.

Cellulose is the colourless material which composes the
cell-walls and woody fibre of plants, and so occurs to a large
extent in our food. In man however it does not undergo
digestion and therefore need not be further considered here.

In herbivorous animals cellulose undergoes digestive changes, and forms
an important constituent of their food. In this case the digestion is mainly
effected through the intermediation of micro-organisms, and results in the
formation of acetic and butyric acids and marsh gas, besides other substances
In certain invertebrata a true cellulose-digesting ferment [r.ytase) is secreted by
the walls of the alimentary canal.

57

CHATTER III

THE BLOOD

Section 1
THE FORMED ELEMENTS OF THE BLOOD

The blood, which circulates through all parts of the living
body and comes into close relationship with all the tissues,
acts as a medium of communication between the cells in
the interior of the bod}' and those on the surface. Thus it
carries the absorbed foodstuffs, which have been taken up by the
cells lining the alimentary canal, to all the other cells of the
body, and from these receives in exchange their waste products,
CO.^ and urea, or some precursor of these substances, to dis-
charge them through the intermediation of excretory cells on
the surface or lining involutions of the outer surface of the
body, such as the cells of the skin, kidney, and lungs.

It is evident that the composition of the blood must be
always varying, according to the nature of the tissues it has
just traversed, and these variations will be more fitly con-
sidered when we come to the discussion of the activities of the
various tissues. But we find that the blood has a certain
power of regulating its composition, or perhaps this function
must be ascribed to the various tissues through which the
blood passes. However this may be, the fact remains that
the blood has an average composition which it is our duty
in this chapter to describe, and round which its composition
varies only to a certain (definite) extent.

The blood of man and most vertebrates is a red opaque
liquid, rather viscous, and to the naked eye homogeneous.
Arterial blood, i.e. the blood in the pulmonary veins, left side
of the heart, and the arteries generally, is bright scarlet ;
while venous blood, i.e. blood in the systemic vems, right
heart, and pulmonary artery, is of a bluish-red hue.

Shaking up venous l)lood with air or oxygen changes it to

58 PHYSIOLOGY

arterial blood, and we shall see later that the bright colour
is due to the formation of a loose combination of one of the
constituents of the blood, haemoglobin, with oxygen. This
combination is normally formed in the lungs, and is robbed
of its oxygen in the tissues.

On microscopic examination the blood is found to consist
of a nearly colourless fluid, the liquor sanguinis or hlood-
plasma, holding in suspension an enormous number of solid
bodies, the red and white blood-corpuscles.

The colour of the blood is entirely due to the red corpuscles.
These are, in man, non-nucleated biconcave discs about g-gV o
of an inch in diameter, and a third of this in thickness. The

Fig. 16.

Non-nucleated red blood-discs of human blood. On the right of the
figure the corpuscles are seen on edge. (Swale Vincent.)

colour of a single corpuscle is yellow, the red colour being
apparent only when large numbers of them are seen together.
They form about 40 per cent, of the total mass of the blood,
there being about five million red corpuscles in every cubic
millimetre of blood.

They are soft, flexible, and elastic, so that they can readily
squeeze through apertures and canals narrower than them-
selves without being permanently distorted. Each red cor-
puscle consists of a framework or stroma composed chiefly of
protein material, containing in its meshes or in a state of
loose chemical combination with it, a red colouring matter,
haemoglobin, to which is due the colour of the corpuscles and
of the blood itself.

By treating the blood with weak solutions of tannic or
boracic acid, a separation occurs between the haemoglobin
and the stroma. The haemoglobin appears as a small ball

THE BLOOD 59

near the centre of a colourless blood-disc, or it may be ex-
truded and lie just outside the stroma. If the plasma be made
denser by evaporation or l)y addition of salts to it, water
diffuses from the corpuscle into the plasma, and the corpuscle
shrinks and becomes wrinkled or crenated. If on the other
hand the plasma be diluted, water diffuses from the surround-
ing medium into the corpuscle, which swells up and becomes
spherical.

It is found that in a 0*9 per cent, solution of sodium chloride
the red corpuscle of mammalian blood neither gains nor loses
in volume. In solutions of less concentration the corpuscle
swells, while in those of greater concentration the corpuscle
shrinks and becomes crenated. These facts show that the
external limiting layer of the corpuscle is impermeable to
sodium chloride, but permits the easy passage of water to
equalise the concentration within and without the corpuscle.

This movement of water is due to the fact that dissolved
substances, like gases, are always tending to expand within
their solvents, a tendency which gives rise to diffusion from
places of higher to those of lower concentration, or to a
pressure (oswo^ic pressure) on any membrane or wall which
is permeated by the solvent but which prevents the passage
of the dissolved substances. When the corpuscles are im-
mersed in a weak salt solution, the osmotic pressure within the
corpuscle is greater than that outside, so that the corpuscle
expands, and may indeed burst if the difference of concentra-
tion is sufficiently great. In solutions of higher concentra-
tion, the external osmotic pressure is greater than that in the
corpuscle, and water is squeezed out through the limiting
layer, so that the corpuscle shrinks.

It is evident that these changes of form will occur only
when the corpuscles are immersed in a solution of some sub-
stances which cannot penetrate the corpuscle. Most neutral
salts {e.g. NaCl, Na.SO^, KNO3 &c.) belong to this category.
A solution of urea, on the other hand, behaves towards the
corpuscles like distilled water. If some red corpuscles be
added to a 1 per cent, solution of urea in normal saline solu-
tion (0-9 per cent. NaCl), they neither shrink nor swell ; and if
the mixture be centrifuged, and the corpuscles and super-
natant fluid analysed separately, the percentage of urea in the
two cases will be found identical — though there will be a great

60 PHYSIOLOGY

preponderance of sodium chloride in the supernatant fluid.
There are a large number of substances besides water to which
the corpuscles are permeable (and in this respect they resemble
most other vegetable and animal cells), e.g. alcohol, chloro-
form, ether, etc. Speaking generally, we may say that animal
cells are freely permeable to all those substances which are
soluble in fats and the allied lipoid substances, cholesterin,
lecithin, and protagon, which are invariable constituents of all
living cells. If, for instance, we wish to stain a living cell,
we must choose some dye-stuff which is soluble in this class
of bodies.

In birds, amphibia, and fishes, the red corpuscles differ from those of
mammals in being nucleated. Those of the frog for instance are oval struc-
tures, each containing an oval nucleus with a well-marked nuclear network.
The hajmoglobin is diffused through the protoplasm of the cell-body, and does
not extend to the nucleus. Mammals during the early part of their foetal life
also possess nucleated red corpuscles. These however soon disappear entirely,
to make way for the ordinary non-nucleated red discs. In the camel the red
corpuscles are oval in shape like those of the frog, but possess no nucleus.
They are also much smaller than those of the frog.

The colourless corpuscles, or leucocytes, are rather larger
than the red (^-gVo ii^ch in diameter), and much fewer in
number, there being only one white corpuscle to about 300 to
600 red.

They are colourless nucleated masses of protoplasm very
similar to the simple organism described in the Introduction
as the amoeba. Like this they have the power of moving
from place to place, of taking up food particles, and probably
of reproduction by fission.

Several varieties of leucocytes exist in the blood. The
most numerous variety, the ' polymorphonuclear ' leucocyte,
presents a nucleus which is lobed or composed of several parts
united by fine threads. The protoplasm contains some very
fine granules which have only a faint affinity for acid dyes
such as eosin.

More sparse are the leucocytes known as ' hyaline.' These
possess only a single round or oval nucleus, and their proto-
plasm is free from granules.

About 5 per cent, of the leucocytes present a mass of
coarse highly refracting granules in their protoplasm. These
granules stain intensely with eosin and other acid dyes, and
are therefore designated eosinophile. The nucleus is lobed or
reniform.

THE BLOOD

61

The fourth variety represented m the figure is the hjmijho-
cyte. This consists of a large round nucleus surrounded by
a thin layer of hyaline protoplasm. It is derived from the
lymphatic glands, and probably represents an immature form
of the hyaline leucoc^'te.

Fig. 17.

Various forms of leucocytes, a. Eosinophile corpuscle, h. Ordinary
polynuclear leucocyte (' neutrophile '). c. Hyaline corpuscle.
d. Lymphocyte.

Very rarely we find a fifth form of corpuscle contain-
ing granules which stain deeply with basic dyes, such as
hsematoxylin or methylene 1)1 ue, and are therefore called
hasophile.

Besides the red and white corpuscles, a third formed
element has been described under the name of blood -platelets.
These are small bodies, disc-shaped or irregular, about one
quarter the diameter of a red corpuscle, and are always to be

Fig. 18.

Blood-corpuscles and blood-platelets, within a small vein.
(Schafer, after Osier.)

observed on examining the blood immediately after it has left
the body. They have also been called haematoblasts, on the
assumption that they were precursors of the red blood -
corpuscles. These platelets have been observed m normal
circulating blood, but it seems probable that they may be
added to by a process analogous to one of precipitation in
the plasma as it commences to die or to cool down.

62

PHYSIOLOGY

Chemistry of the Bed Blood-corpuscles

We have already mentioned that these can be regarded as
consisting of two parts, the haemoglobin and the stroma, pro-
bably in a state of loose chemical combination.

By various means it is possible to destroy this combina-
tion and to dissolve out the haemoglobin, leavmg the colour-
less, swollen-up stroma floating in the plasma. The effect of
this is to make the blood darker but more transparent. In
this condition it is spoken of as ' laky blood.'

Blood may be made laky by the following means :

(a) Addition of a small amount of ether.

(6) Free dilution with water.

(c) Alternate freezing and thawing.

{d) Addition of bile salts ; and various other ways.

If this blood be allowed to stand in a cool place for an
hour or two, a mass of crystals is deposited, which consist of

Fio. 19.

^1

^:k ^-^

Crystals of oxyheemoglobin. 1. Fioin rat.
3. From squirrel.

'2. From guinea-pig.

oxyliasmoglobin. This crystallisation occurs very readily in
the blood of some animals, such as the rat, guinea-pig, and
dog ; much less so in that of others, such as man, rabbit, and
sheep.

Oxyhmnoglohin thus obtained and purified by recrystal-
lisation forms rhombic prisms or tablets of a 'dark-red colour
(Fig. 19). It is a compound of a protein with an iron-
containing residue (haematin), and is distinguished from all
other proteins by the ease with which it crystallises. Its
percentage composition probably varies slightly in different
animals.

THE BLOOD 63

Elementary analysis of haemoglobin crystals from the
blood of the horse gave the following results :

per cent.

Carbon 51-15

Hydrogen 6*76

Nitrogen 17-94

Sulphur 0-389

Iron 0 336

Oxygen ........ 23-425

The empirical formula for haemoglobin calculated from
this would be —

The most important property of haemoglobin is its power
of uniting with a definite proportion of oxygen to form an
easily dissociable compound, oxyhaemoglobin. One gram of
haemoglobin will combine with about 1-5 c.c. of oxygen
(measured at O'' C. and 760 mm. pressure). This compomid
can be dissociated again by various agencies, such as heat or
simple exposure to a vacuum, and we shall see, when talking
of respiration, how very valuable to the organism is this easy
dissociability of the oxyhaemoglobin molecule.

If carbon monoxide gas be led through a solution of
oxyhaemoglobin, the oxygen is replaced by an equivalent
proportion of CO, so that a more stable compound, CO-
haemoglobin, is formed ; and this in its turn can be split
up by nitric oxide gas with the formation of NO-haemo-
globin. Thus the order of stability of these three compounds
would be —

NO-haemoglobin.
CO-haemoglobin.
O.j-hsemoglobin.

The poisonous properties of CO gas are due to this power
it has of turning out the oxygen from the oxyhemoglobin,
thus depriving the tissues of the oxygen which is normally
carried to them by the red corpuscles.

Oxyhaemoglobin is a brighter red and slightly less soluble
than haemoglobin. Solutions of the latter are dichroic,
appearing green by reflected and bluish-red by transmitted
light.

The reduction of oxyhaemoglobin to haemoglobin is easily
effected by various reducing agents, such as ammonium sul-

64 PHYSIOLOGY

phide or Stokes' fluid (an alkaline solution of ferrous tartrate).
This change in the colour of the compound is accompanied
by a very evident change in its absorption spectrum.

Dilute solutions of oxyhsemoglobin placed in front of the
slit of a spectroscope give a very pronounced absorption
spectrum, showing two black l)and8 between Framihofer's
lines D and E. On adding a few drops of Stokes' fluid to the
solution and warming gently, these two bands disappear, and
are replaced by a single band, rather fainter and broader than
the 0„Hb bands, and situated between them. On shaking
the solution up with air, the bands of O^Hb return, only to
disappear again when it is allowed to stand.

Carhoxylimmoglohin has a very similar spectrum to oxy-
hsemoglobin, but is a much brighter red. This difference in
colour is best observed on diluting the blood, when oxyhaemo-
globin acquires a yellowish tint, while the pink colour of CO-
hsemoglobin is retained so long as any colour is visible. The
most important distinction between the two kinds of blood
lies, however, in the fact that CO-htemoglobin is unaltered
by the addition of ammonium sulphide or Stokes' fluid.

Another compomid of hajmoglobin with oxygen is methce-
moglohin. This substance, although not of normal occurrence
in the body, is found in urine and in blood whenever there
is a sudden breaking down of red corpuscles with the setting
free of excess of htemoglobin hi the blood plasma. It may
be prepared by the addition of potassium ferricyanide, per-
manganate, or other oxidising agent to the blood, or to a
solution of haemoglobin. It is a chocolate-brown substance,
crystallisable, and gives a distinct absorption band in the red
between the Fraunhofer lines C and D. On treatment with
a few drops of ammonium sulphide, the methaemoglobin is
converted into haemoglobin, and this on shaking with air
will re-form oxyhaemoglobin. This reduction cannot be
effected by simple physical means, such as exposure to a
vacuum, and it seems probable that methaemoglobin contains
exactly the same relative amount of oxygen as oxyhaemo-
globin, but in a different state of combination, thus^

,0 0

Hb( I Hbf

\0 ^0

Oxyha?moglobin. Metlifemoglobin,

THE BLOOD 65

It is interesting to note that, on treating oxyhaemoglobin
with potassium ferricyanide, the whole of its oxygen is given
off in the free state, the ferricyanide only then attacking the
reduced hasmoglobin and oxidising it again (but in a different
way) to methaemoglobin.

This fact has beeu utilised by Haldane in devising an easy metliod for
determining the oxygen capacity of any given sample of blood {i.e. the total
amount of oxygen which the blood can hold in combination).

A measured quantity of arterial blood is placed in a bottle and laked by the
addition of some weak ammonia. A small tube containing potassium ferri-
cyanide is then placed in the bottle, which id then closed and connected by a
rubber tubing with a graduated gas burette containing water. The bottle is
then inverted so as to mix the ferricyanide solution with the blood. All the
combined oxygen of the oxyhasmoglobin is given off, and its volume determined
by reading off the amount of water displaced in the gas burette. Care, of
course, must be taken to keep the temperature of the whole apparatus constant
during the operation.

Hsemoglobin is very easily destroyed by various means
(heat, alcohol, weak acids, and strong alkalies), being split
up into an iron-containing pigment, haematin, and a protein
residue, which is called glohin. The latter can be prepared
by treating the pure haemoglobin with weak hydrochloric
acid, which dissolves and splits up the haemoglobin. The
globin can then be precipitated by the addition of ammonia.
Although coagulable by heat it presents many analogies with
the group of proteins which have been described as Jiis tones,
and can therefore be included for the present in this class.

Hcematin (C32H3|)N^0.3Fe), when dried and purified, forms
a bluish-black crystalline mass, insoluble in water and alcohol,
but easily soluble in acids or alkalies in alcoholic or watery
solutions. It forms compounds with acids and alkalies which
are known as acid and alkaline haematin, each of which gives
a characteristic absorption spectrum.

With hydrochloric acid it forms a crystalline hydrochloride
known as hcemin. This compomid is prepared with extreme
ease, and this fact, combined with the very definite appearance
of its crystals, renders it a very delicate test for blood.

To prepare hamin crystals a little dried blood, haemoglo-
bin, or haematin is heated with a minute crystal of common
salt and glacial acetic acid, and then allowed to cool. Haemin
crystallises out, and can be recognised on examination under
the microscope. The crystals are dark l)rown, sometimes

5

66

PHYSIOLOGY

nearly blaclc, and present the form of vliombic plates, often
arranged in radiating bundles.

Alkaline haematin is interesting from the fact that it may
be reduced by ammonium sulphide and re- oxidised on shaking
with air, just like a solution of O.Hb. The spectrum of oxy-
alkaline hsematin shows one very indefinite absorption band

Fig. 20.

Absorption spectra of haemoglobin and its derivatives. 1. Oxy-
hsemoglobin. 2. lleduced haemoglobin. 3. Methipmoglobin. 4. Al-
kaline metliffimoglobin. 5. Acid hsematin in ether. 6. Alkaline
haematin in rectified spirit. 7. Eeduced haematin. 8. Acid hfema-
toporphyrin. 9. Alkaline htematoporphyrin. (From MacMunn.)

close to D. Eeduced alkaline haematin gives two sharp
absorption bands, similar to those of oxyhaemoglobin, but
rather nearer the blue end of the spectrum (Fig. 20).

A body similar to, if not identical with, reduced alkaline
haematin, Juemochromogen, is formed when haemoglobin is
warmed with caustic potash in a vessel from which all air has

THE BLOOD 67

been driven out by the passage of a stream of hydrogen or
other neutral gas.

If pure haemin be treated with ammonium sulphide, it
is reduced to haemochromogen. If to this solution globin
(prepared from haemoglobin) be added, and the mixture
allowed to stand for some days, it is found that reduced
haemoglobin is formed. It is interesting to note that egg-
white may be used in this experiment instead of globin,
showing that other proteins can take the place of globin in
the haemoglobin molecule.

Other derivatives of haemoglobin are —

a. Hcematoporphyrin (C,,;H,gN20;3), or iron-free hiematin,
is easily prepared by the action of strong sulphuric acid on
blood, oxy haemoglobin, or haematin, or by the action of 10
per cent, hydrochloric acid on reduced haemoglobin, the
separation of the iron from the rest of the molecule taking

Fig. 21.

Hffiiain crystals.

place with greater readiness in the absence of oxygen. It
forms a deep purple solution with characteristic spectrum in
the acid, from which it is precipitated as a black powder on
free dilution with distilled water. It is isomeric with
bilirubin. With alkalies it forms alkaline hcematoporphyrin,
with spectrum differing somewhat from the acid compound.
Htematoporphyrin is found in minute traces in normal urine,
but may occur in large amount in urine after poisoning by
sulphonal. Hsmatin may be regarded as consisting of two
haematoporphyrin groups linked together by means of one
atom of iron, which also attaches an oxygen atom, as is
represented by the formula

h. Hydrohilirubin (C-jaH^^N^O-) is produced by the action
of tin and sulphuric acid on an alcoholic solution of haematin.

68 PHYSIOLOGY

c. HcBmatuidi)i (probably identical with bilirubin) occurs
as orange-red rhombic tables in old blood-clots in the body.

The STROMA may be obtained from laky blood by the
addition of dilute sulphuric acid or acid sodium sulphate, by
which the swollen -up stromata are shrivelled up ; they may be
collected by allowing the liquid to stand, or by means of the
centrifuge. On chemical analysis they are found to consist
chiefly of nucleo-proteins. They are soluble in weak alkalies,
and on prolonged gastric digestion give an insoluble residue,
rich in phosphorus (nuclein). On extraction with alcohol
and ether they yield a certain amount of lecithin, cholesterin,
and fats.

Important constituents of the red corpuscles are the salts
and water. The salts are chiefly potassium and phosphoric
acid compounds, there being very little chlorides present, and
little or no sodium (cf. the serum).

The corpuscles contain about two-thirds of ilieii" total
weight of water.

Life-history of the Bed Blood-corpuscles

There can be no doubt that a continual destruction of red
blood-corpuscles is going on in the body. Thus an animal
secretes every day by the agency of the liver a considerable
amount of bile, containing a pigment, bilirubin. This pig-
ment can be shown to be derived from the haemoglobin of
the red blood -corpuscles. In cases where an effusion of blood
has taken place mto the brain or the connective tissues, we
often find some months after the lesion that the corpuscles
and red pigment have disappeared, and that the connective
tissue in the vicinity contains a number of yellowish-brown
crystals, known as haematoidin crystals. These crystals are
identical in form, composition, and reactions with bilirubin,
the colouring matter of the bile.

Under normal circumstances however, the conversion of
haemoglobin into bile-pigment, as we shall see later on, takes
place exclusively in the liver. It is found that if, by the
injection of poisons such as pyrogallol or toluylene diamine, a
number of red corpuscles are broken up and destroyed, setting
free haemoglobin in the blood-plasma, there is marked increase
in the amount of ))ile-pigmcnt formed by the liver ; and a
similar increase may be brought about by the injection of

THE BLOOD 69

solutions of pure haemoglobin into the blood. What is the
chemical change involved in this conversion ?

From a comparison of the formula of hfematin (C.j.,H3„N_,
OgFe) with that of bilirubin (C,,;H|^N203), we see that the
change is associated with a loss of iron ; and we find, as a
matter of fact, that in all cases in which there is an increased
iKcmafoJijfiifi (destruction of red corpuscles), there is at the
same time an accumulation of iron in the liver. This ac-
cumulation is especially well marked in cases of pernicious
anfemia. It seems prol)able that, under normal circumstances,
the ha3moglobin is broken up in the liver, part of the hsematin
molecule being transformed into bilirubin and turned out of
the body with the faeces, while the iron is stored up in the
liver to assist in the formation of fresh htiemoglobin or new
red blood-corpuscles.

Tlie presence of iron in the liver cells may be easily demonstrated in fresh
or alcohol-hardened specimens bj- treating a cut sm'face or section succes-
sively with potassium ferroeyanide and dilute hydrochloric acid. After
severe blood destruction the whole liver may present on this treatment a
deep-blue colour, due to the fomnation of iron ferroeyanide.

We have not yet been able in the laboratory to convert
hfematin directly into bilirubin. Iron-free hsematin or
hsematoporphyrin is however very nearly allied to bilirubin,
the empirical formulpe of these two bodies being identical.
We can moreover by the action of reducing agents o1)tain
identical products from haematin and bilirubin. Thus by
treating haematin with tin and hydrochloric acid or by acting
on bilirubin with sodium amalgam, a body, hydrobilirubin, is
produced, which apparently belongs to the same class of
bodies as urobilin, a pigment occurring in small quantities in
the urine. There is no doubt that this latter pigment can be
derived from bilirubin under the influence of putrefactive
organisms, and it is in this way that the urobilin of the faeces
(the so-called stercobilin) is produced.

It is evident then that the pigments excreted from the
body in the urine and f feces are derived from haematin, and
therefore that a disintegration of the red blood -corpuscles
must be continually taking place.

Since, in a healthy animal, the amount of corpuscles in
the blood remains approximately constant, a continual pro-
duction of new corpuscles must go on to take the place of

70

PHYSIOLOGY

those destroyed and discharged to form l)ilo and urinary
pigments. There is considerable doubt as to the exact mode
and place in which this regeneration occurs, and the process
seems to be quite different according as we consider the
foetal or adult condition. We may therefore consider first
the formation of red corpuscles in the eml)ryo and new-l)orn
animal.

The red corpuscles at an early stage of fontal life are
nucleated, like those of the frog or l)ird. Li the vascular
area of the chick, nests of nuclei are found embedded in

Fig. 22.

a -" ,„

Section of red marrow of mammal (Bohm and Davidoff). a, e, ery-
throblasts ; b, reticulum ; c, mj'eloplax ; c7, g, marrow cells ; /, a
marrow cell dividing ; li, a space which was occupied by fat.

colourless masses of non-difierentiated protoplasm. A little
later it is seen that these nuclei are all surrounded with
a differentiated portion of the protoplasm, which now con-
tains hemoglobin, the intervening undifferentiated portions
having become more fluid and representing the future
blood-plasma. Very soon the masses of protoplasm become
channelled and connected with one another and with the
large vessels coming from the heart, and the fully formed
blood moves on into the general circulation in response to
the heart-beat.

According to Schafer, non-nucleated blood-discs may be

THE BLOOD

71

produced in a veiy similar fashion. Towards the end of
foetal life we find in the developing connective tissue branched
masses of protoplasm containing nuclei. These nuclei how-
ever are not wasted on mere oxygen carriers but are entirely
used to form the endothelium of the capillary wall ; and
non-nucleated red corpuscles are developed by a simple
differentiation of the central part of the protoplasmic mass,
the parts of the protoplasm between the corpuscles again
appearing to furnish the material for the fluid plasma.

This process however seems to come to an end within
a few days after birth. In order to find the seat of blood

Fir,. 23.

Section of red marrow of pigeon (Denys). Ic, eosinophile leuco-
cytes ; eg, fat cells ; e, nucleus of endothelial cell of blood-vessel ;
ca, blood capillary ; er, erythroblasts lying within vascular endo-
thelium ; gir, fully formed red corpuscles.

production after this period, the} best method is to increase
the activity of the process b}^ inducing an abnormally large
destruction of corpuscles, either by the injection of poisons or
by the actual removal of blood. If the animal be killed when
by such means its blood-forming powers have been called
upon to the utmost, the only organ i or tissue of the body
which exhibits any sign of hypertrophy* is the red marrow of
the bones. Ordinarily in the adult animal this red marrow is
found occupying only the spaces of the cancellous tissue of
the ribs and vertebrre, and at the ends of the long bones.
But after bleeding it may be found occupying a large extent

7'2 PHYSIOLOGY

of the shafts of the bones. On microscopic examination it is
found that, of the numerous cells which compose this tissue,
myelocytes, osteoblasts, marrow and fat cells, the only
elements present in excess are nucleated cells containing
haemoglobin in their protoplasm. Many of these cells are in
a state of active division, and all intermediate stages can be
found l»etween the daughter-cells, containing well-formed
nuclei and stained with haemoglobin, and the ordmary non-
nucleated red blood-disc, the nuclei apparently degenerating
and undergoing solution or extrusion from the cell. The
capillaries in the red marrow are bounded by walls which
may be imperfect, thus admitting the entry of the newly
formed corpuscles into the circulating blood. According to
some authorities, the large red cells are themselves derived
from colourless nucleated cells, the so-called erythroblasts.
Among the complex of cells forming the red marrow it is
very difficult to make certain of this fact, but there seems to
be little doubt that such is the case in the bird. If we
examine the red marrow of the pigeon we find that the
capillary walls are perfect, but are lined internally by a layer
of blood-forming cells (Fig. 23). In this layer all stages can
be found between the colourless erythroblast and the mature
oval nucleated red blood-corpuscle, which is characteristic of
this class of animals.

The occasional occurrence of nucleated red blood-corpuscles
in the spleen, especially after great loss of blood, has been
regarded by some physiologists as a proof that this organ also
takes part in blood formation. It seems more probable that
the chief function of the spleen in this regard consists in the
destruction by its cells of inefficient or weakened corpuscles, and
that it is rather a blood-destroying than a blood-forming organ.

We need at present only mention the view put forward by Hayem and
others that the red blood-discs are produced in the circulating blood by a
gradual modification of the blood-platelets or liDematoblasts.

We have no evidence to tell us how long a red corpuscle
lives, or how long it can carry on its functions before it is
broken up in the liver or spleen and cast out of the body.
Experiments, such as injection of the blood of a bird into a
mammal when the introduced blood-corpuscle can be always
identified, naturall_y give us no idea of the duration of activity
of a normal corpuscle.

THE BLOOD 78

Since iron is an essential constituent of hfemoglobin, it is
evident that our food must contain enough iron to restore the
loss of it in the corpuscles. The amount however need be
only very small if it were all assimilated, for the whole blood
of an average-sized man does not contain more than about
2-5 grms. Fe.

Inorganic forms of iron, such as the iron salts, are how-
ever absorbed only in very small quantities, and there is
some probability that a good deal of the htemoglobin is re-
integrated from an organic form of iron contained in the
food, called hsematogen — a protein belonging to the group of
nucleo-proteins and containing iron in a state of intimate
chemical combination. After administration of organic iron
salts, this metal may be demonstrated in the absorbmg villi
of the intestine. It is difficult however to determine exactly
the amount of iron absorbed, since the main channel for
excretion of this substance, as for most of the other heav.y
metals, is the intestmal tract. Thus the amount of iron which
can be recovered from the fneces is no index to the amount of
iron which has escaped absorption.

Chemistry of White Blood-corpiificlefi

The chemistry of the white blood-corpuscles is the same
as that of any indifferent animal cells. It can be studied
most conveniently on the leucocytes of lymphatic glands.
These are found to consist almost entirely of bodies belonging
to the class of nucleo-proteins. The extract of these cells
on treatment with acetic acid gives a precipitate of nucleo-
protein, which is soluble in weak alkalies. The solution
produces intravascular clotting on injection into the blood-
vessels. Besides the nucleo-proteins, the leucocytes contain
lecithin, fats, and cholesterin, and often glycogen, in addition
to various nitrogenous extractives. Their salts are similar
to those of the red corpuscles, and contain a preponderance
of potassium salts and phosphates.

Origin of White Blood-corpuscles

The various kinds of leucocytes probably differ in their
mode of origin. There seems little doubt that the hyaline
corpuscles are derived from the lymphocytes, which are found

74 PHYSIOLOGY

ill the lymphatic glands and enter the blood witli the lymph-
stream by way of the thoracic duct.

Many authorities ascribe a similar mode of origin to the
chief or polynuclear leucocytes. These corpuscles occur
mainly in the blood, and have been seen in a state of division,
so that it is most probable that they reproduce themselves by
direct cell division in the blood-stream itself.

The eosinophile corpuscles are found in large numbers in
the connective tissue in various parts of the body, especially
in the red marrow of bones. They probably represent a migra-
tory tissue sui generic (perhaps of a glandular nature), and
are derived from similar cells by division in the blood-stream
or in the connective tissues.

Estimation of Blood-corpuacles

In order to count the corpuscles, a known small volume of blood is diluted
with some indifferent fluid (such as 0-9 per cent. NaCl solution), and a drop of
this placed in a small cell on a glass slide, the bottom of which is ruled with
squares. The depth of the cell and the size of the squares being known, it is
easy to count the corpuscles lying on each square under the microscope, and
from this to estimate the number present in a cubic millimetre of undiluted blood.

Thus in Gowers' hremocytometer the graduated glass cell is I millimetre
deep, and each square is -^ millimetre each way.

Five cubic mni. of blood are drawn into a graduated capillary tube, and
then blown into a ' mixing vessel ' containing sodium sulphate solution (sp. gr.
1025). The mixture is well stirred and a drop placed in the middle of the cell,
and the cell covered. In a few minutes the corpuscles have sunk to the bottom
of the cell, and rest on the squares. The number of corpuscles in ten squares
is counted, and this multiplied by 10,000 gives the number of corpuscles in a
cubic millimetre. In normal blood there are from four to five million cor-
puscles in a cubic millimetre (i.e. an average of forty or fifty to each square of
Gowers' instrument).

Estimation of Hcpinoglobin

To estimate the amount of hremoglobinin a given sample of blood, 20 cubic
mm. are taken and diluted with water, until the mixture is equal in tint to
a permanent standard coloured solution made with glycerin and carmine, and
corresponding in tint to blood diluted 100 times (Gowers' haemoglobinometer).
Thus the number of times the blood must be diluted to bring it to a standard
tint divided by 100 gives the percentage amount of haemoglobin present, the
normal amount being taken as 100.

In von Fleischl's ha>moglobinometer the specimen of blood is always diluted
to the same extent ; but the standard of comparison is a wedge of coloured
glass, which can be slipped to and fro till its tint exactly equals the tint of the
sample of diluted blood placed in a glass cell by the side of the wedge for com-
parison. The sliding wedge is graduated to indicate the percentage amount of
haemoglobin present compared with the normal. Thus if the tint of the blood
is equal to the wedge at 100, the blood contains the normal amount of hfemo-
globin ; if at 50, half that amount ; and so on.

THE BLOOD 75

Section 2
THE COAGULATION OF THE BLOOD

The most striking property of blood is that of clotting
when it is shed. If blood be drawn from an artery or vein
into a vessel, in from two to three minutes it becomes rather
viscid. This viscidity increases till the whole mass of blood
solidifies to form a jelly-like mass, exactly occupying the
volume of the original fluid blood.

After about an hour, yellowish drops exude from the sur-
face of the clot, and this exudation continues till the clot has
shrunk to half its former dimensions, and floats in a clear
yellow fluid (the serum).

Thus, as a result of standing, the blood has been resolved
into solid clot and fluid serum. On examining the clot under
the microscope, we find that it consists of all the corpuscles
enclosed in a meshwork of fine fibrils (Fig. 24).

Fig. 24.

Network of fibrin, after washing away the corpuscles from a film
of blood that has been allowed to clot ; many of the filaments
radiate from Httle clumps of blood-platelets. (Schiifer.)

If however, directly the blood is drawn, it be whipped with
a bundle of twigs or anything presenting a large rough surface,
the latter becomes covered with a stringy mass, and we find
that the blood has lost its power of setting to form a jelly.
This stringy mass is called fibrin, and it is evident that the
coagulation of the blood is due to the appearance in it of these
fibrils of fibrin, which form a network enclosing in its meshes
the corpuscles and the remaining fluid part of the blood.
This network then contracts, squeezing out the fluid, which
appears on the surface of the clot as the serum.

Fibrin obtained by whipping fresh blood, or by washing
away the corpuscles from a clot, exhibits the following pro-
perties :

It is insoluljle in water or in dilute saline solutions. In
stronger solutions, such as 10 per cent, potassium nitrate, it

76 PHYSIOLOGY

is very slowly dissolved, but is altered in the process, the
solution containing not fibrin but proteins Ijelonging to the
globulin class. It swells up in dilute HCl (0-2 per cent.), and
if digested with it at a temperature of 40' C. slowly dissolves,
with the formation of acid albumen or syntonin. If shreds of
fibrin are suspended in water and heated to boiling, they are
converted into coagulated protein, losing the property of swell-
ing up in dilute HCl. The general reactions and constitution
of fibrin show that it belongs to the class of proteins.

The serum, the other end-product of the reactions which
determine coagulation, is a transparent yellowish fluid, con-
taining about 7 to 9 per cent, total solids. Of these, nearly
eight parts are protein in nature. Proceeding on the lines of
the conventional classification laid down in the second chapter,
we may separate two distmct proteins in the serum — serum -
glol)ulin or paraglobulin, and serum-albumen. The serum-
globulin may be thrown down by saturation with magnesium
sulphate, or by adding to the serum an equal volume of a
saturated solution of ammonium sulphate. It is also thrown
down if the serum be dialysed against distilled water, show-
ing that it is insoluble except in the presence of a certain
amomit of neutral salt.^ On heating, it coagulates at about
75° C. An imperfect separation of paraglobulin may be
effected by diluting the serum with twenty volumes of distilled
water, and adding a trace of acetic acid or passing a stream
of CO., through the liquid. On removing the globulin pre-
cipitate, the filtrate still contains 3 to 5 per cent, of a protein
belonging to the albumin class, known as serum-albumen,
which is solul)le in distilled water, not precipitated by satura-
tion with magnesium sulphate, but totally precipitated on
saturatmg with solid ammonium sulphate. The filtrate from
this last precipitate is perfectly free from proteins. Solutions of
serum-albumen coagulate on heating between 77° and SS'' C.

By the method of fractional heat-coagnlation three varieties of serum-
albumen have been separated. But in the absence of further chemical i^roof
the value of the separation so effected must be regarded as doubtful.

' It has been shown lately that the precipitate obtained from serum on
saturation with MgSO^, or half saturation with ammonium sulphate, really
comprises two bodies : —

(a) A true globulin, called euglobuHn, insoluble in pure water, and identical
with the precipitate obtained on dialysis.

(b) A pseudo-globulin, soluble in distilled water, and therefore remaining in
solution when the salts are removed by dialysis.

THE BLOOD 77

The other constituents of the serum mchide extractives
such as urea, sugar (in small traces), and about 1 per cent,
inorganic salts, of which sodium chloride, carbonate, and
phosphate are the most important.

We have now to consider the processes which lead to the
formation of fibrin in shed blood. In order to analyse these
processes it is necessary to slow the process of coagulation.

Clotting is favoured by the following influences :

Exposure to high temperature (up to 50" C).

Contact with foreign surfaces (as when the blood is whipped
with a bundle of twigs).

It is retarded or prevented by-
Exposure to cold (l)lood may be kept fluid almost in-
definitely at a little above 0" C).

Mixture with various salts, such as magnesium or sodium
sulphate, or common salt. The blood is received mto one-
third its volume of a saturated solution of magnesium sul-
phate, or into an equal volume of half-saturated sodium
sulphate solution.

By receiving the blood from the vessels directly into a
solution of a soluble oxalate in such proportions that the
resulting mixture contains 1 in 1,000 of oxalate.

Injection of albumoses (' peptone ') or of leech extract (also
an albumose) into the veins before the blood is drawn.

Contact with the lining membrane of a living blood-vessel.
Thus if we ligature the jugular vein in a horse at two points,
the blood in the intervening part will remain fluid for many
hours. In fact, two such ' living test-tubes ' may be prepared,
and the blood poured in a thin stream from one to the other
without coagulating.

If blood be drawn from an artery or vein in a bird, without
coming in contact with the surrounding tissues, it does not
clot. Clotting can be at once induced by adding a small frag-
ment of tissue, or a watery extract of any of the bird's tissues.

If blood which has been prevented from coagulating by
one of these methods be allowed to stand in a cool place, the
blood-corpuscles, which are heavier than the plasma, gradually
sink to the bottom, leaving a clear supernatant layer of plasma,
which can be pipetted or siphoned oil".'

' This process is much shoitened by using a centrifugal machine. This
consists essentially of a horizontal wheel, with slots cut in it in which tubes are

78 PHYSIOLOGY

Plasma prepared in this way perfectly free from formed
elements can be easily made to clot. Cooled plasma clots
directly its temperature is allowed to rise ; salt plasma on
simple dilution ; oxalate plasma on the addition of a soluble
salt of lime ; peptone plasma on dilution and passage of
a current of CO^.

The clot formed is colourless, and contracts after forma-
tion just like the clot formed in the whole blood. It only
difiers from the latter in containing no corpuscles : in fact it
is pure fibrin.

Hence it is evident that the hluud-plasma contains within
itself the precursors of Jihrui.

We may therefore represent the processes occurring in
coagulation schematically as follows :

Clotting of blood at rest

Blood

Blood-corpuscles Plasma

\

I I

Fibrin Serum

Clot

Clotting of whip2)ed blood

Blood

Blood-corpuscles Plasma

Serum Fibrin

Defibrinated blood

What are these precursors ? If plasma prepared in either
of the foregoing methods be saturated with common salt, a
sticky white precipitate is produced. This may be collected
on a filter and washed w'ith saturated salt solution to remove
all traces of adhering plasma. If we dissolve this substance

suspended. These tubes are filled with the blood, and the wheel made to re-
volve about 2,000 times per minute. The tubes swing out to a horizontal
position, and the centrifugal force causes all the heavier particles to collect at
the ends of the tubes, so that in half an hour the blood-corpuscles form
a compact mass at the bottom of the tubes.

THE BLOOD 79

in dilute salt solution, the solution (at the ordinary tempera-
ture) soon becomes viscid and clots, the clot after a while con-
tracting and separating out a serum, which is found to contain
a protein belonging to the globulins. Denis, the discoverer of
this precipitate, called it plasmine, and supposed that clotting
consisted essentially in a splitting up of this simple soluble
body into two bodies, one of which was insoluble (fibrin) and
the other soluble (serum globulin).

Later on Alexander Schmidt found it possible to separate
this plasmine into two substances, which he called fibrinogen
and fibrinoplastin. Now the latter is identical with the para-
globulin of the serum, and this, as Hammarsten showed, takes
no part in the process of clotting. We must therefore regard
the fibrinogen as the precursor of fibrin, since it entirely dis-
appears and is replaced by fibrin.

Fibrinogen was originally prepared by passing a current
of CO2 through plasma after dilution with twenty volumes of
water. The separation, however, is much better eftected by a
modification of Denis' original method. Sodium chloride is
added to the plasma until it reaches 15 per cent. This is
conveniently done by adding to each volume of the plasma an
equal volume of a saturated solution of NaCl, containing about
30 per cent, of the salt. A precipitate is gradually produced,
at first granular and then becoming fiocculent and fibrinous.
This precipitate may be washed free from adherent protein
by half-saturated solution of sodium chloride. The pure
fibrinogen thus obtained belongs to the class of globulins,
being insoluble in distilled water but soluble in dilute salt
solutions. The solutions coagulate on heating at the low
temperature of 56° C.

If the plasma which served as the source for the fibrinogen
was sodium sulphate or sodium chloride plasma, the solution
of the fibrinogen may clot on simple standing, being almost
entirely converted into fibrin, only a small trace of protein
being left in solution. The change therefore from fibrinogen
to fibrin involves a process of splitting, in which by far the
larger proportion becomes insoluble. If however we get the
fibrinogen from magnesium sulphate or oxalate plasma, the
solution, although in all other respects identical with that
obtained from sodium sulphate plasma, does not clot on
standing ; and the same is sometimes found with the fibrinogen
solution from sodium sulphate plasma, if the precipitated

80 PHYSIOLOGY

fibrinogen has been very thoroughly washed. In all cases
however a pure fibrinogen solution can be made to clot by
adding to it a drop or two of serum, or of the washings of
a blood-clot. It is evident therefore that some other factor
besides fibrinogen must be present in order to bring about
coagulation. Since this other factor may be in excessively
small quantities, and may, if given time, convert almost in-
definitely large amounts of fibrinogen into fibrin, it has been
regarded as a ferment, and caAled fibrin ferment.

A fairly pure solution of the fibrin ferment may be pre-
pared in the following way. Serum, or chopped-up blood -
clot, is allowed to stand with about twenty times its volume of
absolute alcohol for two or three months. The proteins by
this means are precipitated and rendered insoluble in water,
so that an aqueous extract of the dried precipitate contains
very little protein matter, but is rich in fibrin ferment ; that
is to say, it possesses the power of converting solutions of
fibrinogen into fibrin ; for we can never recognise ferments
except by their action.

We must conclude therefore that the coagulation of the
blood is due to the conversion of a soluble protein present in
the plasma — fibrinogen, into an insoluble protein — fibrin,
under the agency of a ferment, lohich is known as fibrin
ferment or throonbin.

As to the chemical nature of the ferment we know practically nothing. It
is destroyed on heating to 55° C. and is always associated with a certain
amount of protein. It is stated by some authors, on rather insufhcient grounds,
to belong to the class of nucleo-proteins.

What is the origin of this fibrin ferment? It is not
present in the circulating blood, but is formed after the blood
has left the vessels. If blood be received straight from an
artery into a large quantity of absolute alcohol, and the
precipitate extracted with water after two or three months, the
extract is not found to have any power of causing clotting in
solutions of fibrinogen.

Schmidt was of opinion that the colourless corpuscles break
down as soon as they leave the vessels and liberate the ferment.
If horse's blood be received into a vessel placed in ice, and
allowed to stand, it soon separates into three layers : an upper
layer of pure plasma, a thin layer of leucocytes and granules,
and a layer of red corpuscles. If the temperature of the blood
be allowed to rise, it clots throughout, but the clotting begins

THE^BLOOD 81

soonest in the layer of leucocytes, and s tirmest there. If
the clot be divided into three portions, and treated for the
extraction of ferment, the extract from the part of the clot
enclosing the leucocytes and granular matter is much more
active than that from either of the two ends of the tube. Of
course the significance of this experiment depends on the view
we take of the origin of the granular matter. Schmidt looked
on it as the debris of exploded corpuscles, while Wooldridge
regarded it as a precipitate produced by the effect of cold
on the plasma. This latter observer therefore considered that
the ferment was produced, not from the leucocytes but from
the plasma, and that the granular precipitate represented the
precursor or zymogen of the ferment. Later researches by
Hammarsten on the clotting of oxalate plasma have confirmed
this view and thrown light on the necessary conditions of the
change from precursor to ferment. Oxalate plasma will clot
on the simple addition to it of a soluble salt of lime, e.g. CaCL, ;
and the same statement holds good for the fibrinogen prepared
from this plasma by the ordinary methods. If however the
plasma be cooled to 0" C. for two or three days, a granulai
discoid precipitate is produced, and on separating oft' the
plasma and extracting from it the fibrinogen, it is found that
the solution will no longer clot with lime salts, but needs the
addition of fibrin ferment. No effect is produced by adding
the precipitate to the fibrinogen, but if a little calcium chloride
be mixed with the precipitate and the mixture added to the
fibrinogen solution, clotting ensues. This shows that plasma
contains in solution a precursor of fibrin ferment which has
been termed protJtrombin, the conversion of prothrombin into
thrombin being dependent on the action of calcium salts.
The origin of fibrin ferment is however rather more complex.
Oxalate plasma, which has been separated from the preci-
pitate of ' prothrombin,' can be made to coagulate by the addi-
tion of extracts of almost any animal tissues together with
lime salts, and these were therefore supposed to contain pro-
thrombin similar to that obtained by cooling oxalate plasma.
But these extracts, even on mixture with calcium salts, are
found to be without effect on pure solutions of fibrinogen. More-
over, the precipitate produced by cold, if thoroughly washed
before treatment with lime salts, loses its power of evoking
coagulation in fibrinogen solutions. It is therefore concluded

6

82 PHYSIOLOGY

that three factors are necessary for the production of librin
ferment or thrombin, viz. : (1) lime salts ; (2) a substance
present in the precipitate of * prothrombin ' as well as in
most animal tissues (this is called tkrombokinase) ; (3) a
substance present in solution in oxalate plasma, and carried
down adhering to the precipitate obtained on cooling, which
is called thromhugen.

Our present views as to the essential nature of the pro-
cesses concerned in coagulation may be summed up as
follows : —

When blood leaves the vessels there is a disintegration of
the blood-platelets (themselves perhaps derived from ante-
cedent changes in the plasma or from an unstable form of
leucocyte) with a liberation of thromboldnase. This acts upon
thrombogen, already in solution in the plasma, and in the
presence of lime salts gives rise to thrombin. Under the
influence of the ferment thrombin, the fibrinogen present in
the plasma is transformed into fibrin.

These changes may be represented by the following
schema :

Blood^Plasma Blood-platelets (? pre-formed)

Fibrinogen Thrombogen Lime Salts Thrombokinase

Thrombin (fibrin ferment)

Fibrin

This view of the nature of the changes involved in coagulation is borne out
by observations on other forms of plasma, especially of plasma obtained from
birds' blood. This, when obtained with scrupulous cleanliness, so as to avoid
any contamination with dust or with the tissues, remains permanently un-
coagulable. In the plasma got by centrifuging the blood, no blood-platelets
are to be seen and no precipitate is produced by exposure to a temperature of
0° C. We may say therefore that blood-platelets, with their contained throm-
bokinase, are absent from birds' blood, and with them the property of sponta-
neous coagulability. The blood is also free from fibrin ferment, but contains
thrombogen as well as soluble lime salts. It is only necessary therefore to add
thrombokinase, in the shape of a watery extract of any tissue or cells, in order
to cause the formation of thrombin and the conversion of the fibrinogen already
present into fibrin.

IntraiKiscular Clotting

If fibrinogen be really present as such in the circulating
blood, one would expect to produce intravascular clotting by
the injection of solutions of fibrin fei'ment. We find however

THE BLOOD 83

that with our ordinary thrombin solutions practically no
effect is produced. If, however, the very strong fibrin fer-
ments contained in some snake venoms be injected, universal
intravascular clotting (thrombosis), may be produced. On
the other hand, injection of solutions containing throm-
bokinase causes at once clotting of the blood in the vessels.
This is probably the explanation of the action of the extracts
of cellular tissues, containing the so-called tissue-fibrinogens.

A solution, tissue-libriaogen, is prepared by extracting chopped-up thymus
or lymphatic glands with water or normal salt solution. After separating
the suspended cells by means of a centrifuge, the clear tiuid is treated with
acetic acid ; this throws down a precipitate of tissue-librinogen, which
may be dissolved in 1 per cent, solution of sodium carbonate. A few c.c.
of this solution, injected into the jugular vein, causes extensive intravascular
clotting within 30 seconds of the beginning of the injection. In the rabbit
intravascular clotting is practically universal, and this is also the case in the dog
if in full digestion. In the fasting dog the clotting may be limited to the portal
area. In this case the rest of the blood, when drawn off, is found to be incoagu-
lable. We may thus distinguish two phases in the action of tissue-fibrinogens
on the living blood : first, a phase of increased coagulability, resulting in the
production of a clot — the positive phase ; secondly, a negative phase of dimi-
nished coagulability. If the injection be carried out very slowly, or the
solution be dilute, only the negative phase may be produced. Subsequent
injections, however rapid, of a strong solution have no effect, the animal being
for the time protected or rendered immune by the first injection.

Certam histological observations support the view that
coagulation is normally inaugurated by the disc-like precipitate
of prothrombin, which appears to be identical with the blood-
platelets of histologists. If a small vessel be observed under
the microscope, and a small part of the lining endothelium
injured, it is noticed that blood-platelets are deposited on the
injured spot, so as to form a little heap. The platelets seem
to fuse into one another, and finally form a little white mass
of fibrin (white thrombus), which effectually occludes any
opening in the wall of the vessel. This process in the living
body always occurs when a vessel is injured, and is a means
by which the animal is protected from bleeding to death from
any small wound.

It may be well liere to summarise the conditions which determine the
clotting of the various kinds of plasma that have been mentioned in this
section.

1. Cooled horse's plasma contains all the fibrin precursors, and clots on
simple rise of temperature. If however it be cooled for some time and
filtered, the thrombokinase is separated, and the filtered plasma will not clot
without the addition of fibrin ferment.

2. Sodium sulphate and sodium chloride plasma also contain all the fibrin

84 PHYSIOLOGY

precursors and clot on sirople dilution, the salt appearing merely to inhibit
the action of the ferment on the fibrinogen. Magnesium sulphate however
gradually precipitates the thrombokinase and thrombogen. The plasma pre-
pared by the use of this salt contains therefore only fibrinogen, and needs
the addition of fibrin ferment as well as dilution to make it clot.

3. Oxalate plasma, when fresh, contains fibrinogen, thrombokinase and
thrombogen. It needs therefore only the addition of lime-salts. If however it
be cooled and filtered, the thrombokinase is separated, and to induce clotting,
either fibrin ferment or a mixture of thrombokinase (or a tissue extract) and
lime-salts must now be added.

4. Peptone plasma presents many peculiarities, and it is still doubtful how
far the facts gained from its study are applicable to the explanation of the
coagulation of blood under normal conditions. The mere addition of peptone
(i.e. a mixture of albumoses, especially hetero-albumose) to blood does not
delay clotting. It is necessary to inject the peptone in the proportion of
0'3 grm. per kilo body-weight into the veins of a living animal (dog). It seems
that, under the infiuence of the peptone, the liver cells or vascular endothelium
secrete into the blood a substance which hinders clotting, so that the loss of
coagulability is merely a secondary result of the peptone injection. Peptone
plasma resembles intravascular plasma in that it will clot only on addition of
thrombokinase or tissue fibrinogens, and is unaffected by fibrin ferment. It
apparently contains not only a precursor of fibrin ferment, but also a pre-
cursor of fibrinogen, since it yields no precipitate on heating to 56° C,
although, by precipitation with salt and re-solution, the typical fibrinogen
described above results.

5. Leech-extract plasma can be obtained by injecting a decoction of dried
leeches into the circulation, or by adding it to the blood as it leaves the vessels.
The active principle of the decoction is a body allied to an iilbumose, which is
secreted by the buccal glands of the leech, and which has the property of
neutralising and so destroying the action of fibrin ferment.

Main Points in the Composition of the Blood

Specific gravity of whole blood about 1055 ; of corpuscles
about 1085 ; of serum about 1035.

The specific gravity of the blood may be estimated clinically in the follow-
ing way : — A series of mixtures of glycerin and water are prepared, with
specific gravities varying from 1030 to 1070. A drop of blood is then sucked
up into a capillary pipette with its point bent to a right angle, and minute
portions of this drop are expelled into a series of glasses containing glycerin
and water mixtures of various strengths. The red drop expelled from the
pipette will rise or sink in the fluid so long as its specific gravity differs from
that of the fluid. The specific gravity of the mixture in which the blood
neither rises nor sinks is equal to that of the blood, and is the number we want
to know.

The blood is slightly alkalme.

This is best demonstrated by placing a drop on a piece of delicate glazed
litmus-paper, and then wiping it off. The spot where the blood rested is
found to be stained blue.

Blood contains from one-third to half its weight of cor-
puscles. The plasma is resolved by clotting into serum and

THE BLOOD 85

fibrin. The serum contains in 100 parts proteins (consisting
of serum allmmen and paraglobulin) 8 parts ; salts about
1 part ; water about 91 parts.

Tlie paraglobulin and serum albumen occur in varying
proportions. The proportion of paraglobulin to albumen in
one case was 1 : 1*5 (man).

The chief salt present is sodium chloride, which constitutes
60 per cent, of the ash. Next to this comes sodium carbonate
(about 30 per cent.), and besides these two we find traces of
potassium, sodium, and calcium chlorides and phosphates.
Traces of fats, cholesterin, lecithm, dextrose, urea, and other
nitrogenous extractives are constantly fomid in the serum.
The fats are much increased after a meal rich in them, and
may give the serum a milky appearance.

The red corpuscles contam in 100 parts — water 70 parts,
solid constituents 30 parts.

Of the solid constituents, haemoglobin forms nme-tenths ;
the other tenth corresponds to the stroma, consistmg of nucleo-
proteiu, lecithm and cholesterin, and salts. There is a
striking contrast between the salts of the corpuscles and those
in the serum ; the former consisting chiefly of potassium
phosphate, the latter of sodium chloride, which ma}^ be almost
or entirely wanting from the corpuscles.

The Biological Significance of certain Constituents of
the Ser7im.

It has long been known that the serum of some animals
acted as a poison when injected into others, producing exten-
sive breaking up of corpuscles, appearance of haemoglobin in
solution in the urine, and death. The same destructive efiect
of seram on foreign corpuscles may be observed in vitro.
Thus dog's serum causes a rapid destruction of the red
corpuscles when added to defibrinated rabbit's blood, although
there is no appreciable difi^erence between the concentrations
of the sera of the two animals. This relative glohidicidccl
action of the serum may be artificially produced. Thus injec-
tion of the corpuscles of a guinea-pig into a rabbit causes the
serum of the latter to become giobulicidal for the corpuscles
of the guinea-pig. The giobulicidal property is destroj'ed on
heating the serum to 55^^ C.

The giobulicidal or hceviolytic power of the serum depends on the presence
in the latter of two distinct substances, viz. an antibody or avihoceptor, and a

86 PHYSIOLOGY

complement. Thus when rabbit's serum is made hn^molytic for guinea-pig's
corpuscles, by repeated injections of the corpuscles of the latter into the
rabbit, the amboceptor in the rabbit's serum is the direct result of the injection.
It is found that, if this serum be heated to 55° C, it loses its ha!molytic
properties. These, however, are at once restored to it on the addition of some
blood-serum from a normal guinea-pig. It is therefore concluded that serum
normally contains a substance, toxic for corpuscles, which is destroyed at
55° C. This however is unable to act except in the presence of another
substance, the immune body or amboceptor, which is specific for each kind of
corpuscle, and is produced as the direct result of the injection of any foreign
corpuscles into an animal. The amboceptor is not destroyed at 55° C.

The blood sera of various animals have in the same way a
destructive power on certain bacteria, and this action may be
increased by the previous injection into an animal of the
bacteria in question. It is by the development of sucli
bactericidal substances that the animal is in many cases
enabled to react to an infection, or to develop an immunity
after one attack from further attacks of the disorder.

This reaction, viz. the production of ' antibodies ' in the
serum, is not confined to the effects of injecting living
corpuscles or bacteria. Almost any protein, injected into an
animal's veins, evokes the production in the animal of an
antibody, a coaguUn, which has the property of inducing a
precipitate in solutions of the protein which had been injected,
but in no other. The antibody therefore in this case is
specific. In the same way the injection of toxins, the poisonous
products of bacteria, e.g. diphtheria toxin, or tetanus toxin,
causes the development in the blood serum of a corresponding
antitoxin, which has the power of combining with and
neutralising the toxin in question. This fact is made use of
in therapeutics. Horses are injected with increasing doses of
diphtheria toxin. After some time they are bled, and the
blood serum so obtained, when injected into a patient the
subject of diphtheria, neutralises the poison circulating in the
body, and leads in this way to arrest of the disease.

Thus we must conclude that the serum of any individual,
besides the definite chemical substances already described,
contains a large number of * antibodies ' of complex constitu-
tion, which have been produced by the entry into the blood of
bacterial poisons from without, or of ferments from the
alimentary canal, or of proteins from the disintegration of
tissues, and that these substances play an important part in
the defence of the individual against further infection or
spread of any process of destruction.

87

CHAPTER IV

THE CONTRACTILE TISSUES

Section 1
GENERAL CHARACTERS OP MUSCLE

The means b^^ which the organism acts on its environment is
furnished by the contractile tissues, under which term we
inchide all the varieties of muscle, striated and unstriated.

All movements that require to be sharply and forcibly
carried out are effected by means of striated muscular tissue,
and as these movements are in nearly all cases under the con-
trol of the will, the muscles are often spoken of as voluntary.

Unstriated muscular fibres (often termed involuntary ' )
form sheets or closed tubes surrounding the hollow viscera,
and by their slow prolonged contractions serve to maintain
and regulate the flow of the contents of these organs.

Intermediate in properties between these two classes we find
heart muscle ; this, though striated, presents important histo-
logical differences from striated voluntary muscle. We shall
study this form more fully when we come to consider the
physiology of the whole vascular s^'stem.

The properties of the contractile tissues have been most
fully investigated in voluntary muscles, the most highly dif-
ferentiated members of the group ; we shall therefore consider
this part of the subject at length, merely indicating at the end
in what points the unstriated involuntary muscles differ from
the striated.

Voluntary Muscle

The voluntary or striated muscles form a large part of the
body, and are known as the flesh or meat. Each muscle is

' The ciliary muscle furnishes an example of a muscle which, though
unstriated, is under the control of the will.

88 PHYSIOLOGY

eml)edded in a layer of connective tissue, and is made up of
an aggregation of muscular fibres, which are united into
bundles ])y means of areolar connective tissue. The individual
fibres vary much in length, and may be as long as 4 or 5 cm.
At each end of the muscle the fibres are firmly united to tough
bundles of white fibres, which form the tendon of the muscle,
and are attached as a rule to bones. Eunning in the con-
nective tissue framework of the muscle we find a number of
blood-vessels, capillaries, and nerves.

On examination of a living muscle, each fibre is seen to
consist of a series of alternate light and dark strife, arranged
at right angles to its long axis, and enclosed in a structure-
less sheath — the sarcolemma. Each band may be considered
to be made up of a number of prisms (sarcomeres) side by
side, with interstitial substance between them. The muscle

Fig. 25.

Muscular fibre of a mammal, examined fresh in serum, highly
magnified. (Schiifer.)

prisms of adjacent discs are connected to form long columns
(primitive fibrillse, or sarcostyles). Each muscle prism is
more transparent at the two ends than in the middle, thus
giving rise to the appearance of light and dark striae. In the
middle of the light band is a line or row of dots (often appear-
ing double), called Krause's membrane.

The development of this regular cross and longitudinal
striation is closely connected with the evolution and specialisa-
tion of the muscular function, i.e. contraction. Contractility
is among others a function of all undifferentiated protoplasm.
Cells so constituted can only effect slow and weak contrac-
tions. Directly a specialisation of function is necessary and
some cell or part of a cell has to contract rapidly in response
to some stimulus from within or without, we find a differentia-
tion both of form and of internal structure. In many cases.

THE CONTRACTILE TISSUES

89

as in the devfiloping muscle of the embryo or the adult
muscles of manj^ mvertebrates, this difterentiation affects only
part of the cell, so that while one part presents the ordinary

Fig. 27.

Fig. -2(5.

Fig. 2G.— Muscle-fibre of an ascaris. a. The difi'erentiated contractile
portion of the cell. (After Hertwig.)

Fig. 27. — Muscle-fibres from the small intestine, showing the fine
longitudinal striation. (Schiifer.)

granular appearance, the other half is finely and longitu-
dinally striated, the striation being apparently due to the
development of special contractile fibrillte. In the slowly
contracting unstriated muscle of the vertebrate intestine, the

90 PHYSIOLOGY

longitudinal striation is with difificulty made out ; but as the
muscle rises in the scale of efficiency, the longitudinal
striation becomes more apparent, and in the striated muscle of
vertebrates, and still more in the wonderful wing-muscles of
insects, which can perform three hundred complete contrac-
tions in a second, the longitudinal is associated with and
often apparently subordinated to a transverse striation, due
to the regular segmentation of the contractile fibrillae or
sarcostylefi. Every muscular fibre, which presents any trace
of histological differentiation, maj^ be said to consist of con-
tractile fibrill?e (sarcostyles), each composed of a series of
contractile elements {sarcoufi elementfi or sarcomerefi), and
embedded in a granular material known as sarcoplaam. The
enormous variation in the aspect of muscular fibres from
different parts of the animal kingdom is largely conditioned
by the varying relations, spatial and quantitative, of the
sarcoplasm to the sarcostyles. Thus in the higher vertebrates,
two types of voluntary muscular fibre are distinguished,
according to the amount of sarcoplasm they contain : one
rich in sarcoplasm, more granular in cross-section, and
generally containing htemoglobin ; and the other poor in
sarcoplasm, clear in cross-section, and containing no haemo-
globin. From the fact that the granular fibres are found
chiefly in those muscles which have to carry out long-
continued and powerful contractions, it seems reasonable to
regard the interstitial sarcoplasm as the local food-supply of
the active sarcostyles, although some authors have endowed
the sarcoplasm with a contractile power of its own, differing
only by its extremely prolonged character from the quick
twitch of the sarcostyles. The connection between structure
and activity of the muscle-fibres is well shown by Fig. 28.

In some animals, such as the rabbit, we find muscles consisting almost
entirely of one or other of these varieties; but in most animals (amongst which
we may reckon frog and man) the two varieties occur together in one muscle,
so that what we have to say about the properties of voluntary muscle, which
rests nearly entirely on experiments with frog's muscle, really has reference to
a mixed muscle, i.e. muscle containing both red and white fibres.

Since the sarcous element represents the contractile unit
of the muscle, a knowledge of its intimate structure should
be of great importance for the theory of muscular contraction.
Unfortunatelv, however, we are here at the limits of the

THE CONTEACTILE TISSUES

91

demonstrably visible. Where every worker has liis oavh in-
terpretation, it is only possible in this book to select one,
which appears to be the most suggestive from the physio-
logical standpoint. Schafer, working on the highly diffe-
rentiated wing-muscle of the wasp, concludes that each

Fig. 28.

Transverse sections of the pectoral muscles of a, the falcon, b, the
goose, and c, the domestic fowl. It will be noticed that the
relative amount of granular or red fibres present varies directly
as the bird's power of sustained flight. (After Knoll.)

sarcostyle is divided by Krause's membranes (the lines in the
middle of each light stripe) into sarcomeres. Each sarcomere
contains a darker substance near tlie centre divided into two
parts by Hensen's disc. At each end of the sarcomere the
contents are clear and hyaline. In the act of contraction, the

Fig, 29.

S.E^

Diagram of a sarcomere in a moderately extended condition, a,
and in a contracted condition, n ; k, k, membranes of Krause ;
H, line or plane of Hensen ; se, poriferous sarcous element.
(Schafer.)

clear material flows, according to Schafer, into tubular pores
in the central dark material.

When a muscle-fibre, killed by osmic acid or alcohol, is
examined under the microscope by polarised light, it is seen
to be made up of alternate bands of singly and doubly
refracting material. The doubly refracting {anifiotropo^is)

92

PHYSIOLOGY

substance corresponds to tlie dark band, and the singly
refracting (isotropoiis) to the light band. If however the
living fibre be examined in the same way, it is fomid that
nearly the whole of it is doubly refracting, the singly refract-
ing substance appearing only as a meshwork with long parallel
meshes corresponding to the muscle prisms. In short, in a
living fibre the muscle prisms are anisotropous, the sarcoplasm
isotropous.

When a muscle-fibre contracts, there is an apparent
reversal of the situations of the light and dark stripes, owing
to the fact that the interstitial sarcoplasm is squeezed out

Fig, 30.

sole.

end arborisation,
muscle-fibre.

sarcolemnia.
— muscle.

Motor end-plates of lizard.

from between the bulging sarcomeres, and accumulates on
each side of the membranes of Krause. The accumulation
of sarcoplasm in this situation makes the previously light
strife appear dark, and the dark strife by contrast lighter than
they were before. That there is no true reversal of the striae
is shown by examining the muscle by polarised light, the
two substances, isotropous and anisotropous, retaining their
relative positions.

Every skeletal muscle is connected with the central
nervous system by nerve-fibres, some conveying impressions
from the muscle to the centre, the others acting as the path
of the motor impulses from the centre to the muscle. These

THE CONTRACTILE TISSUES

93

latter -the motor nerves — end in the muscular fibre itself,
by means of a special end-organ -the motor end-plate. The
neurilemma of the nerve-fibre becomes continuous with the
sarcolemma, the medullary sheath ends suddenly, while the
axis cylinder ramifies in a mass of undifferentiated protoplasm,
containing nuclei, and lying in contact with the contractile
substance of the muscle immediately under the sarcolemma.

Fig. 31.

Tib. ant. Ion

Gastrocnemius.
Tib. post.
Tibia.

Sartorius.

Add. magn.
Gracilis.

Tendo Acbillis.

Muscles of hinder extremity of frog (after Eckcr)

So far as we can tell at present, the ultimate ramifications
of the axis-cylinder end freely and do not enter into organic
connection with the contractile substance itself.

Most of our knowledge on the subject of muscle has been
derived from the study of the gastrocnemius and sartorius
muscles of the frog. The position of these muscles is shown
in the accompanying diagram (Fig. 31). The gastrocnemius

94 PHYSIOLOGY

which, with the attached sciatic nerve, is most frequently
employed as a nerve-muscle preparation, forms a thick belly
immediately under the skin at the back of the leg, and arises
by two tendons from the lower end of the femur and the
outer side of the knee-joint. The two tendons converge
towards the centre of the muscle, uniting about its middle,
and from them a number of short muscular fibres arise,
passing backwards and dorsally to be inserted into a flat
aponeurosis covering the lower half of the muscle, which ends
in the tendo Achillis. On account of this irregular arrange-
ment of the muscular fibres, the gastrocnemius can only be
employed when the contraction of the muscle as a whole is
the object of investigation. The effective cross-area of the
fibres is much greater than the actual cross-section of the
muscle, so that, while the actual shortening of the gastro-
cnemius is but small, its strength of contraction is con-
siderable.

The sartorius muscle consists of a thin band of muscle-
fibres running parallel from one end of the muscle to the
other. It lies on the ventral surface of the thigh, arising
from the symphysis pubis by a thin flat tendon, and is
inserted by a narrow tendon into the inner side of the head
of the tibia. On account of the regularity with which its
fibres are disposed, this muscle is of especial value in
experiments on the local conditions of a muscle-fibre accom-
panying its activity. When a greater mass of approximately
parallel fibres is necessary, recourse may be had to a pre-
paration consisting of the gracilis and semi-membranosus
muscles together. This latter muscle lies dorsally to the
gracilis muscle which is shown in the illustration.

THE CONTEACTILE TISSUES 95

Section 2
EXCITATION OF MUSCLE

A muscle may be caused to contract in various ways.
Normally it contracts only in response to impulses starting
in the central nervous system and transmitted down the
nerves. But contraction may be artificially excited in
various ways m a muscle removed from the body. If we
make a muscle-nerve preparation {i.e. a muscle with as long
a piece of its nerve as possible attached to it), such as the
gastrocnemius of the frog with the sciatic nerve, we find we
can cause contraction by various forms of stimuli — mechanical,
thermal, or electrical -applied to the muscle or the nerve
(direct and indirect stimulation). Thus the muscle responds
with a twitch if we pass an induction shock through it or its
nerve, or pinch either with a pair of forceps. Or we may
use chemical stimuli, and cause contraction by the application
of strong glycerin or salt solution to the nerve.

These experiments do not prove conclusively that muscle
itself is irritable. It might be urged that, when we pinched
or burnt the muscle, we stimulated, not the muscle substance
itself, but the terminal ramifications of the nerve in the
muscle, and that these in their turn incited the muscle to con-
tract. But the independent excitability of muscle is shown
clearly by the following experiment.

A frog, whose brain has been previously destroyed, is
pinned on a board, and the sciatic nerves on each side
exposed. A ligature is then passed round the right thigh
underneath the nerve, and tied tightly so as to close eflectu-
ally all the blood-vessels supplying the limbs, without inter-
fering with the blood-supply to the nerve. Two drops of
a 1 per cent, solution of curare are then injected into the
dorsal lymph-sac. After the lapse of a quarter of an hour
it is fomid that the strongest stimuli may be applied to the
left sciatic nerve without causing any contraction of the
muscles it supplies. On the right side however, stimulation
of the nerve is as efficacious as before. Both gastrocnemii
respond readily to direct stimulation, showing that the

96

PHYSIOLOGY

muscles are not affected by the drug. Since both sciatic
nerves have been exposed to the influence of the curare, it
is evident that the difference on the two sides cannot be due
to any deleterious effect on them by the curare. We have
also excluded the muscles themselves ; so we must conclude
that the curare paralyses the muscles by affecting the termi-
nations of the nerve within the muscle, and probably the
end-plates themselves.

This experiment therefore teaches us that muscle can be
excited to contract by direct stimulation, even when the
terminal ramifications of the nerve within it are paralysed,
so that stimulation of them would be without effect.

The same fact may be demonstrated in a different way by
means of chemical stimuli. It is found that whereas strong

Fig. 32.

The ramification of the nerve-fibres within the sartorius muscle of
the frog, showing the freedom of the lower portion of the muscle
from nerve-fibres. (Kiihne.)

glycerin excites nerve-fibres, it is without effect on muscle-
fibres ; while on the other hand weak ammonia is a strong
excitant for muscle, but is without effect on nerve. Thus if
the frog's sartorius be dissected out and the lower end dipped
in glycerin, no effect is produced. On snipping off the lower
third of the muscle and then immersing the cut end in glycerin,
a twitch at once occurs. The lower end contains no nerve-
fibres (Fig. 32), and it is only when a section contaming
nerve-fibres is exposed to the action of glycerin that con-

THE CONTRACTILE TISSUES 97

traction takes place. On the other hand, mere exposure of
muscle to the vapour of dilute ammonia causes contraction
(and subsequent death), although the nerve to the muscle
can be immersed in the solution without any excitation being
produced.

Of all the different stimuli that we have mentioned as
capable of exciting muscular contraction, the electrical is
that most frequently employed. It is easy, using this form,
to graduate accurately the intensity and duration of the
stimulus. At the same time the stimulus may be applied
many times to any point on the muscle or nerve without
killing the part stimulated, whereas with other forms of
stimulus it is difficult to obtain excitatory effects without
injuring to a greater or less extent the part stimulated.

Two forms of electrical stimuli are employed, — the make
and break of a constant current, and the induction currents
of high intensity and short duration obtained from an induc-
tion coil.

Constant current. — As a source of constant current a
Daniell's cell is generally employed {vide Appendix). In

Fig. 33.

Kaihodej Anode.

this cell the copper is the negative and the zinc the positive
element. The current therefore passes in the cell from zinc
to copper, and outside the cell from copper to zinc. If
therefore wires be attached to the zinc and copper, the wire
attached to the former will be the negative, and that to the
latter the positive pole. If we connect such wires with the
nerve or muscle of a nerve-muscle preparation (as in Fig. 33),
the current will flow from copper to the nerve at A, and along
the nerve from A to K. At K the current will leave the
nerve to flow to the zinc of the battery, so completing the
circuit. The point at which the current enters the nerve
{i.e. the point of the nerve connected with the positive pole

7

98 - PHYSIOLOGY

of tlie battery) is called the anode, and the point at which
the current leaves the nerve is called the kathode. The wires
by which the current is conducted to and from the nerve are
called the electrodes.

If a weak current from a Daniell's cell (or any other form
of battery) be passed through a muscle or any part of its
nerve, we find that at the make of the current the muscle
gives a single sharp contraction — a muscle-twitcli. No effect
is produced during the passage of the current or when it is
broken, the muscle remaining perfectly quiescent.' If the
current is now increased we find that the muscle responds to
both make and break, remaining however quiescent during
the passage of the current. Using a current of moderate
strength, we find the contraction due to make is more energetic
than that due to break.

Thus stimulation is caused l)y the make and break of a
constant current, the make stimulus being more effective than

Fig. 34.

Saitorius clamped in middle and attached to levers at either end.

the break. Besides this difference in intensity, there is a
difference in the point from which excitation starts. A make
contraction starts from the hatliode, a break contraction
from the anode. This is well shown by the two following
experiments.

a. A curarised sartorius muscle of the frog (Fig. 34), with
its bony insertions still attached, is fastened at the two ends
to two electrodes, which are able to swing when the muscle
contracts, and are attached by threads to levers which serve
to record the contraction. The middle of the muscle is then
fixed by clamping it lightly. A circuit is arranged so that

' This statement is not absolutely correct. No propagated contraction, as
a rule, is produced during the passage of a constant current. Careful observation
will show however that there is a state of continued contraction limited to the
immediate neighbourhood of the kathode, which lasts as long as the current is
passed through the muscle.

THE CONTRACTILE TISSUES 99

a constant current can be sent through the electrodes and
the whole length of the muscle. It is found, on making the
current, that the lever attached to the kathode — that is, to the
electrode by which the current leaves the muscle — rises before
the other lever. On the other hand, on breaking the current,
the lever at the anode rises iirst, showing that the anodic half
of the muscle contracts before the kathodic half.

h. The irritability of a muscle, i.e. its power of responding
to a stimulus by contracting, is intimately dependent on the
life of the muscle. If the muscle be injured or killed at any
spot, its irritability at this spot will be therefore diminished
S)r destroyed. Hence, if we stimulate a muscle at the injured
spot, no contraction will ensue. This fact may be used to

Fig. 35.

kathode j^ anode(injured)

contraction at make

anode rn kathode (injured)

no contraction at make.

b
Diagram to show the effect of local injury on the excitability of a
muscle, b, battery ; wj, muscle. The arrows indicate the direction
of the current.

demonstrate the production of excitation at kathode on make,
and at anode on break of a constant current.

A muscle with parallel fibres, such as the sartorius, is
injured at one end, and a constant current passed, first from
the injured to the uninjured end, and then in the reverse
direction. It is found in the former case, when the anode
is on the injured part (which is therefore less excitable), that
break of the current is ineffective, and in the latter, when the
kathode is on the injured surface, that the make stimulus is
ineffective, showing that the part excited corresponds to the
kathode at make and to the anode at break.

Induced currents. — In using these the muscle or nerve is
stimulated by the current of momentary duration produced
in the secondary circuit of an induction coil by the make or

100 PHYSIOLOGY

break of a constant current in the primary. The strength of
the shock is graduated by moving the secondary nearer to or
farther away from the primary coil.

Using this mode of stimulus, it is found that the con-
traction on break of the constant current is much stronger
than that on make. It must not be imagined however that
there is any contradiction between this and the fact that the
make of a constant current is a stronger stimulus than the
break.

When we put a muscle in the secondary circuit and make
a current in the primary, there is a current of momentary
duration induced in the secondary ; so that there is a current
made and hrohen through the muscle, and the same thing
takes place again when the primary circuit is broken. It has

been shown that, when we use currents of such short dura-
tion, the break stimulus is ineffective ; so in both cases,
whether we make or break the current in the primary circuit,
we are dealing with a make stimulus in the muscle. The
difference in the efficacy of make and break induction shocks
is purely physical, and depends on the fact that the current
induced in the secondary coil on make is of slower rise and
smaller potential than that produced at break. (See
Appendix.)

We see therefore that the efficiency of an electrical stimu-
lus depends on the rate of variation of the current employed,
and within wide limits is proportional to this rate. Tf, instead
of suddenly diminishing and increasing the current passing
through an irritable structure, we carry out the change
gradually, no excitatory efi'ect is produced, even although the
current may finally attain a considerable strength. This

THE CONTEACTILE TISSUES 101

fact may be demonstrated with the help of the rheocord
(Fig. 36), which consists of a simple wire ab through which
a current is led. Two wires pass from a and a movable rider c
to the nerve or muscle. It is evident that if c be in close
proximity to a, no current will flow through the muscle.
But as c is pushed towards b, the current through the nerve
gradually increases. It will be found that if the rider be
moved slowly from a to b, or in the reverse direction, no
effect is produced, whereas a quick movement in either
direction causes excitation. We may say therefore that the
excitatory effect of a current increases with —

1. The intensity of the current.

2. The rate of change of the current.

3. (In the case of nerve) The length of nerve through
which the current passes.

The second of these conditions needs however some
correction. As we increase the rate of change of current, by
employing in the case of induced currents more and more
rapid alternations, we find that the excitatory eftect, instead
of increasing, begins to diminish and finally disappears, so
that high frequency currents of enormous tension can, as in
Tesla's experiments, be led through the body without any
apparent physiological effect. On the other hand, by using
more sluggish forms of irritable tissue, we may find that
even our induction shocks are too rapid for effective excita-
tion. Thus the red muscles of the slow-moving tortoise react
better to the slow make than to the sudden break induction
shock, and many forms of unstriated muscle are unaffected
by either make or break shock. We must conclude there-
fore that for each tissue there is an optimum rate of change
varying with the character of the tissue, at which the energy
necessary to produce a response is at a minimum. This
optimum rate of change is spoken of by Waller as the
* characteristic ' of an irritable tissue, and has been deter-
mined by him for nerve.

A minimal stimulus is the weakest stimulus that will produce a contraction.
A maximal stimulus is one that produces the strongest contraction a muscle is
capable of under the effects of a single stimulus. A suhmaximal stimulus is any
strength of stimulus between these two extremes.

102

PHYSIOLOGY

Section 3

THE MECHANICAL CHANGES THAT A MUSCLE
UNDEEGOES WHEN IT CONTEACTS

Change of Form

The most evident change about a muscle when it con-
tracts is of form. It becomes shorter and thicker, its bulk
remaining unaltered.

To study this change more closely, it is necessary to
obtain a graphic record of the contraction. For this purpose
the femur, to which the gastrocnemius of the muscle-nerve
preparation is attached, is clamped firmly, and the tendo
Achillis attached by a thread to a light lever, free to move

Fig. 37.

Arrangement of apparatus for recording simple muscle- twitch.

round an axis at one end. The point of this lever is armed
with a bristle (anything that is stifi' and pointed will do),
which just touches the blackened surface of a piece of glazed
paper. This paper is stretched round a cylinder (drum) which
can be made to rotate at any constant speed required. If the
drum is moving, the point of the bristle draws a horizontal
white line on the smoked paper.

If however a single induction shock be sent through the
nerve of the preparation, the lever is jerked up, falling again
almost directly, and a curve is drawn like that shown in
Fig. 38.

THE CONTEACTILE TISSUES

103

A similar curve is obtained if the muscle be stimulated
directly.

In all such graphic records we should have also —

1. A 1 17)16 record. — This is furnished by means of a small
electro-magnet, armed with a pointed lever writing on the
smoked surface. This electro-magnet (time marker or signal)
is made to vibrate 100 times a second (more or less as
may be required) by putting it in a circuit which is made
and broken 100 times a second by means of a tuning-fork
vibrating at that rate. The tmiing-fork is maintained in
vibration in the same way as the Wagner's hammer of an
induction coil.

2. A record of the exact point at which the nerve or muscle
is stimulated. — This may be obtained in two ways :

a. When using the pendulum or trigger myograph, in

Fig. 38.

Curve of single muscle-twitch taken on a rapidly moving
surface (pendulum myograph) (from Yeo).

both of I which the recording surface is a smoked Hat surface
on a glass plate, this latter is so arranged that it knocks over
a key as it shoots across, and so breaks the primary circuit
and excites the nerve or muscle of the preparation. As we
know the exact pomt that the plate reaches when it knocks
over the key, we can mark on the contraction curve the exact
moment at which stimulation took place.

h. If we wish to make and break the primary circuit at
will by means of a key, a small electro-magnetic signal, inter-
posed in the circuit, is arranged to write on the revolving
drum, and so mark the point of stimulation.

In the figure (Fig. 38) the upper line is the curve drawn
by the lever of the muscle as it contracts ; the small upright
line shows the point at which the muscle was stimulated ;

104

PHYSIOLOGY

and the second line is the tracing of the chronograph, every
vibration representing -5^ of a second.

In the pendulum myograph (Fig. 39) a smoked glass plate is carried on a
heavy iron pendulum. At each side the pendulum is armed with a catch,
which fits on to other catches at the side of the triangular box, from the apex
on which the pendulum is suspended. At its lower part the pendulum carries
a projecting piece which can knock over the ' kick-over ' key (k), thus breaking
a circuit in which is included the primary coil of an induction coil. The lever
attached to the muscle is arranged so as to write lightly on the glass plate,
Everything being ready, and the key (k) closed, the pendulum is raised to a, the

Fig. 39.

Simple form of pendulum myograph.

catch (a) is then released, and the pendulum falls at an ever-accelerating rate
and then rises again, gradually slowing off until it is caught again at b.
As it passes by the key it breaks the circuit. A break induction shock is
sent into the muscle or nerve, which contracts, and a curve is obtained
similar to that shown in Fig. 38. Since the rate of the pendulum is constantly
varying throughout its course, it is necessary to have a tuning-fork, or time-
marker actuated electrically by a tuning-fork, writing just below the muscle-
lever.

In the spring myograph, otherwise known as the trigger or shooter myograph
(Fig. 40), a smoked glass plate is also used. ' The frame supporting the glass
plate slides on two horizontal steel wires. To make the instrument ready for
use, the frame is moved to one side, which compresses a short spring. When
the catch holding it. in this position is released by the trigger, the spring

The contractile tissues

105

which only acts for a short space, gives the frame and the glass plate a rapid
horizontal motion ; and the momentum carries the glass plate through the
rest of the distance, till stopped by the buffers. The velocity during this
time is nearly constant, as the friction of the guides is small. Two keys
are knocked over by pins on the frame and break electric circuits. The
relative positions at which the circuits are broken can be altered by a con-
venient adjustment. A tuning-fork vibrating about 100 per second fixed to the
base of the instrument marks the time ; its prongs are sprung apart by
a block between their ends, and the same action which releases the glass
plate also frees the fork by removing the block and allows it to vibrate ; a
writing style then draws a sinuous line on the smoked surface of the moving
glass plate. A muscle lever with a scale-pan attached also forms part of the
nstrument.' '

Fig. 40.

(T^

Diagram of spring myograph, or ' shooter.'

It will be seen that a simple muscular contraction or
twitch, such as we have in Fig. 38, produced by a momentary
stimulus, consists of three main phases :

1. A phase during which no apparent change takes place
in the muscle, or at any rate none which gives rise to any
movement of the lever. This is called the latent period.

2. A phase of shortening, or contraction.

3. A phase of relaxation, or return to the original length.
The small curves seen after the main curve are due to

elastic vibrations of the lever, and do not indicate any changes
occurring in the muscle itself. From the time-marking
below the tracing, we see that the latent period occupies about

' From Catalogue of Camb. Sci. Inst. Co.

106 PHYSIOLOaY

j-g-o of a second, the phase of shortening y^^, and the relaxa-
tion j^ff second.

Thus a single muscle-twitch is completed in about yV of
a second. It must be remembered however that this number
is only approximate, and varies with the temperature of the
muscle and its condition, being much longer in a fatigued
muscle.

It is generally said that, during the latent period, invisible
preparatory changes are taking place in the muscle, and
these changes are supposed to be indicated by the electrical
change accompanying a muscular contraction, which is
generally described as taking place durmg the latent period.
But recent experiments have tended more and more to
shorten the latent period, and it now seems probable that
nearly the whole of the latent period is due partly to instru-
mental inertia, and partly to the mechanical inertia of the
muscle itself. For living muscle is elastic and very exten-
sible, and the effect of contraction of any given part of it will
be first to stretch the adjacent part, and afterwards to move
the part of the muscle to which the lever is attached.'

Sanderson and Burch have measured the mechanical
latency of muscle by a photographic method. The thicken-
ing of the muscle at the point stimulated was recorded
graphically by photographing the outline of the muscle on a
slit, behind which was a moving sensitive plate. Thus avoid-
ing all instrumental inertia, and diminishing the inertia of
the muscle to a minimum, the mechanical latent period was
found to be only 0*0025 second. The electrical change, how-
ever, began at the moment of stimulation, and had reached
its culminating point when the mechanical change was
commencing.

As we should expect from the precedmg paragraph, the
latent period is much increased by increasing the load. It

' The effect of the extensibility of muscle in lengthening the latent
period will perhaps be more intelligible if illustrated by an example. If we
have a weight supported by a rigid wire, and suddenly pull the upper end of
the wire so as to raise the weight, the latter will rise instantaneously. If
however the weight be suspended by a piece of elastic, it will not follow the
pull exactly, but will lag behind, the first part of the pull being occupied
with stretching the indiarubber, and only when this is stretched to a certain
degree will the weight begin to rise. The same retardation of the pull
would be observed if, instead of indiarubber, we used a piece of living muscle.

THE CONTRACTILE TISSUES 107

is also lengthened by cold and fatigue. It is longer in the
red than in the white muscles.

The height of the contraction depends —

1. On the strength of the stimulus.

2. On the load ; the height being smaller, the greater the
weight the muscle has to raise. If the load is graduall}'
increased, a point is reached when the muscle can no longer
raise it. This weight represents the ' absolute force ' of the
muscle. In determining it the muscle is ' after-loaded,' that
is to say, the lever is supported by a screw in its unweighted
position, so that the weight cannot act on the muscle till
the latter begins to contract. In human muscle the absolute
force has been found to amount to 6,000 to 8,000 grams per
square centimetre of cross area of the muscle.

The relaxation of muscle is helped by a moderate load,
and in a normal condition is complete. It is not active —
that is to say, is not due to a contraction in the transverse
direction — but is a passive efiect of extension and elastic
rebound. This may be shown by allowing a muscle to con-
tract while floating on mercury. The subsequent lengthening
on relaxation is very incomplete.

Isotonic and Isometric Contractions

In order to obtain a true curve of a muscle-twitch special precautions are
necessary to avoid the effects of instrumental inertia. When the muscle
begins to contract it imparts a very rapid movement to the lever, which
therefore tends to overshoot the mark and deform the curve. This
source of error may be almost avoided by making the lever as light as
possible, and hanging the extending weight in close proximity to the axle
of the lever, as shown in Fig. 41. Since the energy of a moving mass is

\ , and the tension due to

the weight as well as the velocity on contraction is directly proportional to the
distance of the weight from the axis, it follows that it is better to load the
muscle with 40 grams 1 millimetre from the axis than with 1 gram 40 milli-
metres from the axis, though the tension put on the muscle will be the same in
both cases.

In the first case the energy of the moving mass will be proportional to

J^ ^ ' = 20, and in the second to -^^ — '- = 800, and it is this energy which
2 2

determines the overshooting of the lever and the deformation of the curve.

Since throughout the contraction the lever follows the muscle in its movement,

the tension on the muscle remains the same throughout, and the method is

therefore known as the isotonic method.

In many cases it is of importance to be able to record the development of

the energy (i.e. the tension) of the active muscle apart from any changes in

108

PHYSIOLOGY

its length. For this purpose the muscle is allowed to contract against a strong
spring, the movements of which are magnified by means of a very long lever.
Thus the shortening of the muscle is almost entirely prevented, but the in-
crease in its tension causes a minute but proportionate movement of the spring,
which is recorded by means of the lever. Since in this case the length or
measurement of the muscle remains approximately constant, while the tension
is continually varying throughout the contraction, it is known as the isometric
metJiod. The great magnification necessary in this method introduces serious
sources of error ; but it seems that, if all due precautions be taken to avoid
these errors, the isometric curve differs very little in form from the isotonic,
displaying only a somewhat quicker development of energy at the beginning of
contraction.

Blix apparatus for recording isometric and isotonic curves syn-
chronically (Miss Buchanan), p, the steel cylindrical support
with jointed steel arm to bear the isotonic lever Z, which consists
of a strip of bamboo with an aluminium tip. t, the isometric
lever, also of bamboo, except for a short metal part V in which
are holes for fixing the muscle. The two wires from an induction
coil are brought, one to x , which is in connection with the sup-
port and hence with the metal bar V , the other to y, which is
insulated from the support but connected by a copper wire with
a thin piece of copper surrounding the isotonic lever at the point
where the muscle is attached to it. CI., clamp for fixing the
lower end of the nmsele when an isometric curve is to be taken.
The axis of the isotonic lever is at x, close to which is hung the
weight of 50 grms.

Propagation of Contraction. The Contraction Wave

The whole muscle does not as a rule contract simul-
taneously. When excited from its nerve the contraction
begins at the end -plates and spreads in both directions
through the muscle. The rate of propagation of the con-

THE CONTRACTILE TISSUES

109

traction wave can only be measured by employing a cm-arised
muscle, so as to avoid the wide spreading of the excitatory
change by means of the intra-muscular nerve-endings. For
this purpose a curarised sartorius muscle is taken, stimulated
at one end, and the thickening of the muscle recorded by
means of two levers placed, one near the exciting electrodes
and the second at the other end of the muscle, as shown
in the diagram (Fig. 42). The difference between the latent
periods of the two curves represents the time taken by the
contraction wave in travelling from a to h. By measure-
Fir;. 42.

Diagram of arrangement for recording the contraction wave in a
curarised sartorius.

ments carried out in this way it is found that the rate of pro-
pagation of the contraction in frog's muscle is 3 to 4 metres
per second ; in the muscle of warm-blooded animals it may
amount to 6 metres.

The actual duration of the contraction at any given point
is necessarily smaller than that of the whole muscle, and
amounts in frog's muscle to only 0-05-0-09 second, about
half the duration of the contraction of a whole muscle of
moderate length. The length of the wave is obtained by
multiplying the rate of transmission by the duration of the
wave at any one point. It varies therefore in frog's muscle

110 PHYSIOLOGY

between 3,000 x -05 ( = 150) and 4,000 x -09 ( = 360) millimetres.
Thas the muscle-fibres in the frog are much too short to
accommodate the whole length of the wave, and the contrac-
tion of the whole muscle must be made up of the summated
effects of the contraction wave as it passes from point to point.
Hence the longer the muscle, the more must the contraction
be lengthened by the time taken up in propagation from one
end to another.

Summation of Contractions

If a muscle is stimulated twice in succession, so that the
second stimulus follows the first before the muscle has reached
its maximum shortening, we get a combination of the effects
of the two, which results in a stronger contraction. The
second stimulus has the same effect on the muscle as if the
condition of contraction, which this latter has attained when
the stimulus reaches it, were its normal length.

Thus, if the period that elapses between the two stimuli is
equal to the duration of the first part of the contraction (from

Muscle curves showing summation of stimuli, r and r', the points
at which the stimuli were sent into the nerve. From the first
stimulus alone the curve a b c would be obtained. From r' the
curve d e f is obtained. These two curves are summated to form
the curve a g h i k when both stimuli are sent in at the interval
rr'.

its beginning to the maximum height), the shortening of the
muscle may be doubled. Fig. 43 shows the effect of two suc-
cessive stimuli at an interval of about J^^ second. The two
lower curves represent the contractions which would have
resulted from either of the stimuli alone.

This piling up of one contraction on the other is spoken of
as siimmation.

THE CONTEACTILE TISSUES ]11

Tetanus

If a muscle be stimulated so many times in a second {e.g.
with the interrupted current of an ordinaiy induction coil)
that it has no time to relax between one stimulus and another,
we get a prolonged steady contraction, which is much stronger
than the maximal muscle-twitch, owing to the summation of the
rapidly following stimuli. This condition is called tetanus.

The rapidity of stimulation needed to produce an unbroken
tetanus depends on the duration of a single muscle-twitch, and
varies therefore according to the kind and condition of the

Fig. 44.

Curves showing formation of tetanus (from frog's gastrocnemius),
a. Six stimuli per sec. b. Ten stimuli per sec. c. Thirty stimuli
per sec.

muscle. Thus the rapidity need only be small in the case of
cooled and tired muscles, or of the red muscles of the rabbit
and tortoise. The rate varies from about 1.5 in the case of
red muscles to 30 or 40 for white muscles. For the much
more highly differentiated muscles of insects the rate is
probably very much greater.

Extensibility

Besides the change of form, we find changes in the
elasticity and extensibility of muscle taking place during
contraction.

Living muscle in a perfectly normal condition is distin-

112 PHYSIOLOGY

guished by its slight l)ut perfect elasticity ; that is to say, it
is considerably stretched by a slight force (in the longitudinal
direction), but returns to its original length when the extend-
ing weight is removed. The length to which muscle is stretched
is not proportional to the weight used, but any given increment
of weight gives rise to less elongation, the more the muscle is
already stretched. The accompanying curves show the elonga-
tion of muscle as compared with a piece of indiarubber, when
the weight on it is uniformly increased.

Dead muscle is less extensible and its elasticity is less
perfect. A given weight applied to a dead muscle will not

Fig. 45.

^

Extensibility of indiarubber (a) compared with that of a frog's
gastrocnemius muscle (b).

stretch it so much as when the muscle was alive ; but the dead
muscle does not return to its original length when the weight
is removed.

A contracted muscle on the other hand is more extensible
than a muscle at rest. A gram applied to a tetanised gastro-
cnemius will cause greater lengthening than if it were applied
to the same muscle at rest. At the same time the elasticity
is more perfect — that is to say, when the weight is removed,
the muscle returns more quickly to its original length.

THE CONTKACTILE TISSUES

113

Section 4

THE PRODUCTION OP WORK AND HEAT BY
VOLUNTARY MUSCLE

The External Work done by a Muscle

We have already seen that the height of contraction of
a muscle diminishes as the load is increased. This diminution
in height is at first very slight and is not proportional to the
load, so that the work done hy the muscle, which is measured
hy the product of the weight lifted and the height to which it
is raised, w x h, with increase of weight rises at first quickly
then more slowly to a maximum, and then, on further increasing
the load, sinks.

Fig. 46.

Curve showing the length of a muscle under various loads in the
contracted condition b, and uncontracted condition a. The
double lines a b etc. represent the contracted muscle, while the
long single lines a c etc. show the length of the inactive muscle.

This will be rendered clearer by reference to the diagram
(Fig. 46) representing the lengths of the resting and contracted
muscle with various loads. The lines h^„ h,, etc., are the actual
height of contraction of the muscle when loaded with weights
of 0, 10, 20 grams, etc. The work in each case is given by
ho X 0, h, X 10, h.^ X 20, hg x 30, etc. By inspection it will be
seen that —

O.h^ < lO.h^ < 20.h, < SO.hg > 40.h , > SO.b^.

114 PHYSIOLOGY

In this case therefore the maximum of mechanical work is
obtained when the muscle is loaded with about 30 grams.
This increase of work with increased load shows that the
amount of external work performed by a muscle is not a con-
stant quantity, nor one determined solely by the strength of
stimulus, but is essentially conditioned by the tension mider
which the muscle contracts. The muscle is in fact endowed
with a certain power of adaptation, so that it can respond
with increased efforts or expenditure of energy when it has
more work set it to do. It might be thought that the in-
creased mechanical energy evolved under these conditions
had its origin at the expense of some other form of energy,
such as heat or electrical changes, but it is found that
increased tension augments all the processes of muscle,
including chemical changes and the production of heat.
This excitatory effect of tension on skeletal muscle is aided
in all the higher animals by impulses which pass through
the central nervous system, the nature of which we shall
have to discuss later on when dealing with the question of
so-called * tendon reflexes.' The phenomenon however is
common to all forms of contractile tissues, and is indeed
much better marked in such forms as the heart-muscle and
the unstriated muscular fibres of the viscera. One may
occasionally find that the application of a slight load to a
skeletal muscle actually increases the height of the contrac-
tion, especially if the muscle be not after-loaded. In the
heart-muscle an increase of tension within physiological limits
causes invariably increased contraction — a fact of very great
importance for the physiology of compensation in heart
disease. This excitatory influence affects not only the strength
of contraction but also the automatic, rhythmic, and conduct-
ing power of the muscle ; and m some cases, as in the snail's
heart, the rate of beat is absolutely determined by the tension,
the heart stopping altogether if the tension be reduced to
nothing.

The Production of Heat

The experience of everyday life teaches us that muscular
exercise is associated with increased production of heat. A
man walks fast on a frosty day to keep himself warm ; and

THE CONTEACTILE TISSUES 115

we find this observation confirmed when we investigate the
contraction of an isolated muscle outside the body.

Thus, if a frog's muscle is tetanised, its temperature rises
from 0-14" to 0-18° C, and for each single twitch from 0-001°
to 0-005° C.

It is evident that such small changes in temperature as
0-001" cannot be estimated by ordinary thermometric methods.
For this purpose a thermopile must be used.

The construction of a thermopile depends on the fact that, when the
junctions of a circuit made of two metals are at different temperatures, a
current of electricity generally flows through the circuit. This current can be
measured by means of a galvanometer, and is proportional to the difference of
temperature between the two junctions. Thus in the circuit (Fig. 47) composed

Fig. 47.

COOL

Antimony ■ 1 ] Bismuth

Q

WARM

of two metals, antimony and bismuth, if the upper junction be cooled, there
will be a current flowing from antimony to bismuih in the direction of the
arrow, and this current will within limits ;^be proportional to the difference of
temperature.

To measure the production of heat during muscular contraction, a small
flat thermopile (containing four or six elements composed of iron and German
silver) is fixed with one of its ends between two frog's gastrocnemii. Another
exactly similar pile, but reversed, is placed between two other gastrocnemii,
which are kept resting and at a perfectly constant temperature. The
arrangement of the piles is shown in the diagram (Fig. 48). So long as the
two piles are at the same temperature no current flows ; but, with a sensitive
galvanometer, the slightest difference of temperature, such as that caused by
the contraction of one pair of muscles, at once causes a deflection of the galvano-
meter, the extent and direction of which enable us to estimate exactly the
seat and amount of heat produced.

Another method of measuring the heat production in muscle takes advan-
tage of the fact that the electrical resistance of a wire increases with a rise of
temperature. In both methods we convert heat into electrical changes, since
our means of judging of electrical differences are more sensitive than is the
case with any other physical change.

In large animals the production of heat in muscular con-
traction can be easily shown bj^ inserting the bulb of a thermo-
meter between the thigh muscles, and stimulating the spinal
cord. The rise of temperature i:)roduced in this way may
amount to several degrees.

116 PHYSIOLOGY

The discovery of exact means of measuring the heat pro-
duction during contraction was naturally utilised to determine
the relation between the heat produced and the work done
under varying conditions. In the muscle as in a steam
engine, we have a conversion of potential energy stored up in
carbon compounds into kinetic energy, which may appear as
work and heat. In the engine there is a definite ratio be-
tween work and lieat. Only a certain small proportion of the
total energy can be utilised as work, the rest being dissipated
as heat. The exact proportion depends on the difference of
temperatures that is available in the machine, and in the best
engines at our disposal amounts to one-tenth. If the machine
does no work, the heat production is increased by the amount

Pre. 48.

ACTIVE MUSCLE RESTING MUSCLE

Diagram of the arrangement for showing the development of heat
during muscular contraction. A B, B A, two thermo-electric
junctions ; G, galvanometer. (After Waller.)

corresponding to the work. The same is true to a certain
extent in muscle. If a muscle be allowed to contract and relax
twenty times when loaded by a weight, the total external work
done will be nothing. If however the weight be attached to
the axle of a wheel, which is provided with a catch so that
the weight can only be drawn up (Fig. 49), and the muscle
be allowed to pull at each contraction on the circumference of
the wheel, at each contraction work is done. It is found that
in the latter case the muscle is less heated than in the former,
and the difference is equivalent to the work done in raising
the weight. But as soon as we begin to alter the work by
altering the weight, we are at once met by the difficulty that
increased tension augments all the properties of the muscle,

THE CONTEACTILE TISSUES

117

and with the same stimuhis both work and heat production
are raised by increasing the load. In fact the maximum
amount of heat is produced when the muscle is made to
contract against a strong spring, so that it cannot shorten at
all (isometric contraction).

In view of the comparison of the muscle to a heat engine,
it becomes interesting to inquire into its efficiency, i.e. the

I'lG. 4'J.

Diagram of Fick's ' Arbeitsanimler ' or muscle crank, a 6 is a
counterbalanced lever, attached to the muscle M at m. When
the muscle contracts, the catch c carries round the circumference
of the wheel D and so coils up the weight W round the axle of
the wheel. When the muscle relaxes, if c._, is in the situation of
the dotted line, the weight pulls the wheel and lever back to its
original position. If, however, c, be applied to D, the backward
movement of the wheel is prevented, and the nmscle is extended
simply by the weight of the lever a b. Thus at each contraction
the weight is drawn a httle higher, and external work is per-
formed by the muscle.

relation of the work to the total energy expended. This
amount is found to vary within very wide limits. In a fresh
muscle the heat energy may be twenty-five times as great as
the work energy, but the heat evolved with each contraction
diminishes with fatigue more rapidly than the work done, so
that the proportion may fall to as low as three to one. In

118 PHYSIOLOGY

the intact animal, in the clog fed on a pure flesh diet, Pfliiger
has calculated that the efficiency may be as great as 48 per
cent. The efficiency of a heat engine is determined by the
difference of absolute temperatures obtaining on the two sides
of the machine ; and since we cannot imagine even minutely
localised changes of temperature in the animal body of more
than a few degrees Centigrade, we must discard altogether
the analogy of the steam engine, and seek some other explana-
tion of the mechanism by which the muscle is enabled to
transmute the chemical energy of its food into work or heat.
It seems probable that the two products, heat and work, are
simultaneous and independent in their origin, and that any
proportion between them, therefore, is accidental. The muscle
is, in fact, not a heat engine but a chemical engine. The
chemical changes are converted directly into pressure changes
leading to change of form of the ultimate contractile element,
and it seems reasonable to suppose that these pressure changes
are directly induced by the osmotic pressure of the products
of chemical change produced as an immediate result of
excitation.

THE CONTEACTILE TISSUES 111)

Section 5
THE ELECTEICAL CHANGES IN MUSCLE

If a current from a battery be passed between two plates
of platinum immersed in acidulated water or salt solution,
electrolysis of the water takes place, bubbles of oxygen
appearing on the positive plate (anode), and bubbles of hydrogen
on the negative plate (kathode). If now we remove the
battery, and connect the two plates (electrodes) by wires
with a galvanometer, it will be seen that a current is passing
through the galvanometer and water in the reverse direction
to the previous battery current. This current is called the
polarisation current, and is due to the electrolysis of the
water that has taken place. The vessel in which the
electrodes are immersed has in fact become a galvanic cell,
the platinum covered with hydrogen bubbles being the positive
element, and that covered with oxygen bubbles the negative
element. Exactly the same process of electrolysis or polarisa-
tion takes place when we pass currents through the tissues of
the body by means of metallic electrodes.

Hence before we can study accurately the delicate elec-
trical changes that may occur normally m living tissues, it
is necessary to have some form of electrodes in which this
polarisation will not occur. The ' non-polarisable ' electrodes
which are most generally used for this purpose are made in
the following way. A glass tube (Fig. 50) is closed at one
end with a plug of kaolin made into a paste with a saturated
solution of zinc sulphate. The rest of the tube is filled with
a similar solution. Dipping into the zinc sulphate solution
is a rod of pure zinc, amalgamated. Just before use, a
plug of china clay made with normal saline solution is put
on the end of the tube, so as to effect a connection between
the zinc sulphate clay and the nerve or muscle which it is
desired to stimulate or lead off". In these electrodes there
is no contact of metals with fluids that can produce dis-
similar ions {e.g. hydrogen or oxygen bubbles) at the surface
of contact, and hence they may be regarded as practically
non-polarisable.

120

PHYSIOLOGY

A more convenient form is that devised by Bm'don-
Sanderson, in which the glass tube is bent into a U (Fig. 51).
The mouth of the tube is closed by a smaller glass tube
plugged with clay, and bearing a plug of normal saline clay.

If a muscle such as the sartorius be removed from the
body, and two non-polarisable electrodes connected with a
delicate galvanometer be applied to two points of its surface,
there will be a deflection of the mirror attached to the
galvanometer, showing the presence of a current in the
muscle from the ends to the middle, and in the external
circuit from the middle (or equator) to the ends. It was
formerly thought that this current was always present in all
normal muscles, and it was spoken of as the ' natural muscle

Fig. 50.
S-yinw- a.

C.

Fig. 51.

Fig. 50. — Diagram of non-polarisable electrode, a. Covered wire.
h. Amalgamated zinc rod. c. Glass tube. d. Saturated ZnSO solu-
tion, e. Plug of zinc sulphate clay. /. Plug of normal saline clay.

Fig. 51. — U-shaped non-polarisable electrodes.

current ; ' the muscle was said to be made up of a series of
electromotive molecules, the equator of each molecule being
positive to the two poles (Du Bois Eeymond). It has been
conclusively shown however (by Hermann and others) that
this current of resting muscle is not a natural current at
all, but is due to the effects of injury in making the pre-
paration. The less the preparation is injured, the smaller
is the current to be obtained from it, and in some contractile
tissues, such as the heart, there may be absolutely no current
during quiescence.

Hermann describes the fact of the existence of currents of
rest thus : — ' In partially injured muscles every point of the
injured part is negative towards the points of the uninjured

THE CONTKACTILE TISSUES 121

surface.' Fig. 52 shows the direction of the current in a
muscle with two cut ends.

When the whole muscle is quite dead, this current of
rest, or 'demarcation current' (Hermann), disappears. The
current is due to the electrical differences at the junction of
living and dying (not dead) tissue. If the sartorius of the
frog be cut out and immersed for twenty-four hours in 0'6 per

L'lu. 52.

Current of rest.

cent. NaCl solution made with tap water {i.e. containing
lime), all the injured fibres die, and the uninjured fibres are
then found to be iso-electric and therefore currentless.

The existence of this current may be demonstrated with-
out using a galvanometer. If the nerve of a sensitive
muscle-nerve preparation (a. Fig. 53) be allowed to fall on an
excised muscle (b), so that two points of the nerve are in

Fig. 53.

contact with the cut end and with the surface of the second
muscle (b), the muscle (a) will contract each time the nerve
touches (b) so as to complete the circuit.

Whatever be the explanation of this current of resting
muscle, there is no doubt that a very definite electrical change
occurs in a muscle when it contracts.

To show this change, we may lead off two points, one on
the cut end and one on the surface of the muscle of a muscle-

122

PHYSIOLOGY

nerve prei^aration, to a galvanometer. We shall then obtain
a deflection of the mirror of the magnet, due to the current of
rest or demarcation current. If now the nerve be stimulated
with an interrupted current so as to throw the muscle into a
tetanus, the ray of light from the galvanometer mirror is
observed to swing back towards the zero of the scale, showing
that the current which was present before is diminished.
When the excitation of the nerve is discontinued, the galvano-
meter indicates once more the original current of rest. Thifi
diminution of the current of rest during activity of a muscle
is spoken of as the * negative variation.''

In carrying out this experiment it is usual to compensate the demarcation
current by sending in a small fraction of the current from a constant cell.
The arrangement of the apparatus is represented in the accompanying dia-
gram. Two non-polarisable electrodes (np) are applied to the surface and

Fig. 54.

cross-section of a muscle (m). These are connected with the shunt of the
galvanometer, one of the wires however being connected with a Pohl's re-
verser (p), and this in its turn with the shunt (s). The two end terminals of the
reverser are connected with a rheochord, through the wire of which (a, b) a
constant current is passing from the Daniell cell (d). By means of the rider (c)
the fraction of current passing through the reverser can be modified to any
extent. The key (k) being open, the muscle is connected with the shunt and
galvanometer, and the direction and extent of the swing noticed. The
key (k) is then closed, and by means of the reverser the current is sent through
the galvanometer in the opposite direction to the demarcation current, and the
rider (c) shifted until the two currents exactly balance each other, and the

THE CONTRACTILE TISSUES

123

needle of the galvanometer returns to zero of the scale. This adjustment is
first made, using only —^ of the total current, and then by means of the
shunt, Y^, ^, and finally the whole current is thrown into the galvanometer.
If this precaution be not taken, much too large a current may in the first
case be sent through the galvanometer, to the detriment of the instrument.
If we know the difference of potential between the two ends of the wire.

the proportion ^ ^ will give us the E.M.F. of the demarcation current.
ab

The

galvanometer needle having by compensation been brought to zero, stimu-
lation of the nerve at (e) by interrupted currents causes the needle to swing
at once in the opposite direction to the first variation. This swing is the
measure of the negative variation or current of action.

The negative variation may also be observed, by means of
a YGYy lightly moving galvanometer, to accompany a single
twitch of the muscle. It has been found to occupy about
.j^ second, and to occur immediately after stimulation.

Since a delicate galvanometer takes some seconds to come to rest when
a current is sent through it, the whole of the variation is over at a time
when the magnet has hardly commenced its swing. Hence to analyse more
fully the electrical change accompanying each separate twitch of the muscle,
recourse must be had to other methods than the direct galvanometric method.

For this purpose we generally use an instrument called the rheotome, by
which we can connect the electrodes on the muscle with the galvanometer at

Diagram of rheotome (Hermann).

varying intervals after stimulation, and by observing the galvanometer readings
at each j^ second after stimulation, can map out the exact course of the current
of action.

The instrument is represented diagrammatically in Fig. 55.

By means of a clock or motor the rod, a b, is made to rotate at any
required rate round a vertical axis at its centre. On either end it carries
two brushes made of fine wire and connected together. The brushes at each
rotation come in contact with the pieces of copper, r r', and when this
happens the primary circuit, k, r', a, r, p, is rapidly closed and broken again.

124 PHYSIOLOGY

thus giving rise to a momentary current in the secondary coil, s, and ex-
citing the muscle, m. In the same way the brushes, b, close the galvano-
meter-electrode-uiuscle circuit, g, t, b, t', 1, ii, ([, each time they brush on the
copper banks, t t'. By turning the disc, a, round, the interval at which the
brushes, b, pass t t', after the brushes, a, pass r r', can be altered at will, and
therefore the interval between stimulation and leading off the current to the
galvanometer.

But there is no need for any demarcation current to be
present in order to show an electrical change accompanying
contraction. In fact we learn much more about the nature
of the excitatory change if we study the electrical behaviour
of a perfectly normal (and therefore currentless) muscle on
stimulation. This can be easily done by means of the rheo-
tome or capillary electrometer.

If a perfectly miinjured regular muscle (such as the
sartorius) be stimulated with a single induction shock at one
end (x) (Fig. 56), and the relative electrical conditions of the

Fig. 56.

Diagram showing diphasic variation of uninjured muscle.

points (a) and (b) investigated, it will be found that as soon as
the excitatory process reaches (a), this point becomes negative
to (b), and there is thus a current in the galvanometer from
(b) to (a). A moment later the two points are equipotential,
as shown by the fact that no current passes through the
galvanometer. A thousandth of a second later this balance
is upset, and now (b) is negative to (a), and the galvano-
meter needle swings in the opposite direction.

Thus every excitation of a normal muscle gives rise to
a diphasic variation, of such a direction that the point
stimulated first becomes negative ' to all other points of the

' The statement that the excited portion of the muscle becomes ' negative,'
though sanctioned by long usage, is not very exact and may give rise to mis-
conception. When we lead off the terminals of a copper zinc couple or cell to
a galvanometer, a current flows outside the cell from copper to zinc and inside
the cell from zinc to copper. In this case we know that the zinc is electro-

THE CONTRACTILE TISSUES

12^

muscle, and this ' negativity ' (to use a loose but convenient
expression) passes as a wave down the muscle, accompanying
or preceding the wave of contraction, and travelling at the
same rate.

This diphasic current of action is shown much more
clearly and easily on a slowly contracting tissue such as the
frog's ventricle.

Fig. 57 represents the photograph of the variation of
the frog's heart, as shown by a capillary electrometer, one
terminal (acid) of which is connected with the base of the
ventricle, and the other (Hg) with the apex. The con-
traction of the ventricle begins at the base. The base
therefore becomes negative, and the column of mercury
moves up (1 to 2). A moment later the contraction has

Fig. 57.

Tracing of diphasic variation of frog's heart taken with
capillary electrometer.

extended to the apex. There is now an equalisation of the
potential between the two terminals, so the mercury comes
back quickly to the base line. Here it stops for about one
and a half seconds. During this time the whole heart is
contracting equally ; both base and apex are thus in a similar
condition, and there can be no difference of potential between
them. The contraction then goes off, but the relaxation, just
as the contraction, begins at the base, and proceeds thence
to the apex. There is thus a small period in which the apex

positive to the copper, and in the same way we must assume that the excited
portion of a muscle is really electropositive to the unexcited portions. When
therefore we speak of any part of a tissue being negative, we are using a con-
ventional expression to indicate the direction of the current in the outer
circuit, and not the electrical condition of the tissue itself. In order to avoid
the confusion which might result from an attempt to replace the loose ex-
pression 'negative' by the correct expression 'electropositive,' Waller has
suggested the employment of the term ' zincative ' to indicate the electrical
condition accompanying excitation. This term also serves to emphasise the
fact that the excited portion, like the zinc in a zinc-copper cell, is the chief
seat of chemical change.

1'2G

PHYSIOLOGY

is still contracted while the base is relaxed, and the apex is
therefore negative to the base. This terminal negativity of
the apex is shown on the photograph by the excursion of the
column of mercury away from the point of the capillary at (4).
The only difference between the electrical changes in this
case and in that of voluntary muscle is that in the latter
all processes are very much quicker, so that as a rule the
point (a) (Fig. 56) has ceased to be negative before the

Fm. 58.

■ 11''

.-aci(I

Diagram of capillary electrometer. Hg., Mercury. The two
terminals are represented as leading off two points at the base
and apex of a frog's heart, a b.

negativity of (b) has attained its full height, and there is
thus no prolonged equipotential stage.

Although in the case of the slowly contracting ventricle of the tortoise,
the record obtained of the electrical changes accompanying its contraction by
means of the capillary electrometer shows with great clearness the diphasic
nature of the variation, and therefore the wave character of the electrical
change, considerable dilliculty is at first experienced when we attempt to inter-
pret in the same way the electrometer record of the electrical response of
voluntary muscle. In this case the electrical change at any spot only lasts about
^7^5 of a second, and there is not a prolonged equij)otential period, as in the case
of the heart. The diphasic nature of the variation is however obvious, if we
compare the electrometer record of an intact and therefore currentless muscle
with that of the change produced by a single stimulus in a muscle in which
one of the leading-off points has been injured, so as to give rise to a demar-
cation current. The two curves are given in Fig. .59, the upper shadowy
tracing being that obtained from the injured muscle. It will be seen that the

THE CONTRACTILE TISSUES 127

distinguishing character of a diphasic variation in the rapidly contracting
striated muscle consists in the fact that the downstroke of the image of the
meniscus is as rapid as the upstroke, whereas the monophasic variation of the
injured muscle presents a slow fall produced by the gradual leakage of the
charge imparted to the instrument back through the electrodes and muscle.
Knowing the constants of the instrument used, it is possible, by measuring
the curvature of this ' spike,' as the record of the diphasic variation is
termed, to determine accurately the electromotive force of the action current
producing the excursion of the electrometer. An exactly similar curve can be
obtained by putting in a current of similar E.M.F. fi'om a battery, first in one
direction for t^^-, of a second, and then in a reverse direction for another ^^^ of
a second.

It must be remembered that a diphasic variation does not mean that one
part of a muscle changes from normal in one direction, and then swings back

Fig. 59.

Superimposed photographs of the electrical variation of the sartorius
in response to a single stimulus. (Burdon-Sanderson.)

past the normal in another direction, but that a change in one direction at one
electrode dies away and is succeeded by a similar change in the same
direction, which also dies away, at the second electrode : that is to say, a
diphasic variation implies a progression of a wave of electrical change between
the leading-off points. It is found that the rate of transmission of this
electrical change in muscle is exactly the same as the rate of propagation
of the wave of contraction, and amounts at ordinary temperatures to about
3 metres per second.

We may now return for a moment to the consideration of
the current of rest observed in injured muscle.

Hermann considers that muscle (or contractile tissue)
becomes negative under two conditions :

(1) In activity.

(2) When dying.

But it must be confessed that the second may be easily
placed under the first head. Section or injury of a muscle
causes a constant stimulation of the adjacent parts. These
parts therefore become negative to the other parts that are
further away from the seat of injury, and we thus get a
demarcation current. Hence we come to the conclusion

128 PHYSIOLOGY

(only paradoxical in terms) that the currents of rest are cur-
rents of action, and are due to excitation around the injured
spot.'

Electrical Organs

An interesting light has been thrown on this question by
a study of the electrical organ in the torpedo and other electric
fishes. In the torpedo is found on each side of the middle
line a kidney-shaped organ forming a considerable mass of
the body- substance and extending from dorsal to ventral side.
Viewed from the surface each organ presents a honeycombed
appearance, due to the fact that it is made up of a number of
prismatic columns running dorso-ventrally, each column con-
sisting of an enormous number of hexagonal discs placed one
above the other. Each column is richly supplied with nerves,
which are derived from large ganglion cells, situate in a
distinct lobe of the brain. Each nerve divides up into eighteen
or twenty branches as it approaches the column, as shown in
the diagram (Fig. 60). Each plate receives nerve-fibres at all
its six corners. On tracing the nerve-fibre into the plate, we
find that every element consists practically of a gigantic motor
end-plate. The axis-cylinders branch dichotomously and form
a close network embedded in granular protoplasm, and rest-
ing on a granular material which represents all that is left of
the striated muscles of the embryo, out of which the electrical
organs have been developed. We have therefore a series of
end-plates separated from one another by laminae of connect-
ive tissue, and so arranged that any electrical changes in the
nerve terminations will be summated somewhat after the
analogy of the summation of efl'ect in a Volta's pile. As a
result we find that, although the electromotive force of the
action current in a single element is only about 0*025 volt (no
greater than that observed in an ordinary nerve or muscle),
yet the E.M.F. of the whole organ compounded of thousands
of these plates attains to several hundred volts, so that, in

' If the demarcation current is really only due to excitation, we should
expect to find it weaker than the action current obtained by exciting the
whole muscle to contract. And this is the case. The E.M.F. of the demar-
cation current of a sartorius equals about 0-05 of a Daniell cell The action
current of the same muscle may attain to an E M.F. = 0-08 of a Daniell cell
(Gotch).

THE CONTEACTILE TISSUES

129

spite of the short circuiting of the current by the water in
which the animal is immersed, a discharge of the organ would
give a painful shock to any one touching the fish, and may
even kill small animals.

We have here an excitable tissue in which the action
current is from the anatomical arrangements of the organ
always monophasic. If an organ or segment of an organ be
cut out of the body, it will be found to present a resting
current, which however declines quickly and may finally
disappear altogether. The direction of this resting current

Fi«. 60.

Diagram of the structure of a column of the electrical organ of the
Torpedo, showing its division into diacs, and the distribution of
its nerve supply. (Fritsch.)

is always the same as that of the discharge. Injury to any
part of the organ or at either electrode alwaj^s increases the
resting current, whereas of course in a muscle the direction of
the resting current is entirely determined by the situation of
the injury. In the torpedo therefore the resting current is
always a current of action due to the slight constant irritation
of the injury ; and there seems no reason why we should
assume a difierent explanation for the resting current in striated
muscle or in nerve.

9

130 PHYSIOLOGY

Secondary Contraction. Rheoscojjic Frog

The negative variation of one muscle may be used to make
another contract.

If the nerve of the preparation (a) (in Fig. Gl) be kid so
as to touch at two points the cut end and surface of the
muscle (b), and the nerve of (b) then stimulated with single
induction shocks, every contraction of (b) will be attended by
a contraction of (a), excited by the negative variation of the

Fig. 61.

Rhcoscopic frog.

current passing through its nerve from the point touching the
cut end to that in contact with the equator of (b).

If the nerve of (b) is tetanised, (a) as well as (b) enters
into a continued contraction. This ' secondary tetanus ' is
of interest as showing that, although the contractions of (b)
are fused, the excitatory process and negative variations are
still quite distinct.

THE CONTRACTILE TISSUES 181

Section 6
THE CHEMISTEY OP MUSCLE

Chemical Composition of Voluntary Muscle

It is impossible to speak with certainty about the chemical
composition of any living tissue, since in the act of analysis
we destroy the life of the tissue ; all we can do in most cases
is to find the proximate principles present in the dead tissue.
But, by using certain precautions, we may learn some interest-
ing facts about the chemistry of living muscle. Muscle of
cold-blooded animals mav be cooled below 0"" C. without losing
its irritability on re-warming and therefore we may say with-
out its life being destroyed. If the living muscle of frogs be
frozen, then minced with ice-cold knives as finely as possible
and pounded in a mortar with four times its weight of snow
containing 0-6 per cent, of common salt, and the mixture
thrown on to a filter and kept at a little over 0° C, an
opalescent fluid filters through. The filters soon get clogged
and therefore must be frequently changed. Their temperature
must not be allowed to rise over 2° or 3° C. This fluid is
called muscle-plasma. If its temperature be allowed to rise
to that of the room, it clots, and the clot soon contracts,
squeezing out a serum, just as in the case of blood-plasma.

The muscle-plasma is neutral or slightly alkaline. When
coagulation takes place however, it becomes distinctly acid,
and this acidity has been shown to be due to the formation of
sarcolaetic acid in the process.

Arguing chiefly from analogy with the blood-plasma, the
muscle-plasma has been said to contain a body, myosinogen,
which is converted when clotting takes place into myosin, and
perhaps other bodies, of which lactic acid may be one.

The exact nature of the proteins in muscle-plasma, as well as of the pro-
tein constituent of the clot, which we have called myosin, is still a subject of
debate. Kiihne, to whom we owe our first acquaintance with muscle-plasma,
described the clot as consisting of myosin, a globulin, soluble in 5 per cent,
solutions of neutral salts, such as NaCl or MgSo^, precipitated by complete
saturation with ]MgSo4, and coagulated on heating to 56° C. In the muscle
serum, obtained after separation of the clot, he found three proteins, one
coagulating at 45° C, one he called an albumate (i.e. a derived albumen), and

132 PHYSIOLOGY

the third coagulating about 75° C, and apparently: identical with serum
albumen. Halliburton extended these researches to the muscles of warm-
blooded animals. He described four proteins as existing in muscle-plasma,
of which two, paramyosinogen and myosinogen, gave rise to the clot of
myosin.

In no case however is it possible to entirely dissolve up the clot when once
formed, and it seems that the so-called solution in dilute salt solutions was
merely an extraction of still soluble proteid in the meshes of the clot. The
latest work on the subject by von Fiirth has shown that if the muscles of a
mammal are washed free of adherent lymph and blood, the plasma obtained
by extraction with normal salt solution contains only two proteins. These
proteins are extremely unstable, and are gradually transformed on standing
into insoluble protein, giving rise to a precipitate in dilute solutions, or
forming a jelly-like clot in strong solutions. The properties of these proteins
may be summarised as follows :

1, Myosin (paramyosinogen of Halliburton). A globulin, coagulating at
about 47°- 50° C, precipitated by half saturation with ammonium sulphate or
on dialysis. Transformed slowly in solution, rapidly on precipitation, into an
insoluble protein, myosin fibrin.

2. Myogen (myosinogen of Halliburton). A protein allied to the albumens
in'that it is not precipitated by dialysis. Coagulates on heating at 55°-G0° C.
It changes slowly into an insoluble protein, myogen fibrin, but passes through
an intermediate soluble stage called soluble myogen fibrin. This latter body
coagulates on heating to 40° C, being instantly converted at this temperature
into insoluble myogen fibrin. It does not seem that any ferment action is
associated with these changes, which we may represent by the following
schema :

Muscle-plasma.

I I

Myosin or Paramyosinogen. | Myogen (Myosinogen of Halliburton,

I Albumate of Kiihne).

I Soluble myogen fibrin.

Myosin fibrin. Insoluble myogen fibrin.

Muscle clot.

Soluble myogen fibrin, which in mammalian muscle-plasma forms only on
standing, exists apparently preformed in frog's muscle. Hence the instan-
taneous clotting of frog's muscle-plasma on warming to 40° C.

The residue left after the expression of the muscle-plasma
consists chiefly of connective tissue, sarcolemma, and nuclei,
and as such contains gelatin (or rather collagen), mucin,
nuclein, and adhering traces of the proteins of the muscle-
plasma itself.

The muscle serum contains the greater part of the soluble
constituents of muscle. These are —

A. Colouring matters. — All red muscles contain a con-
siderable amount of haemoglobin. In many, a special pigment,

THE CONTRACTILE TISSUES 133

probably allied to hsemoglobm, is also present. This has been
named mijolicematin (MacMunn).

B. Nitrogenous extractives. — Of these, the most important
is creatin (C4HgN302 + H20), which occurs to the extent of 0*2
to 0*3 per cent. This substance is found only in muscular
and nervous tissues. Its significance we shall discuss later on
when inquiring into the history of the formation of urea.

Other nitrogenous extractives are —

Hypoxanthin or sarcin, xanthin (both bodies allied to uric
acid), carnin, and a trace of urea.

c. Non-nitrogenous constiticents. — Fats.

Glycogen. The amount of this is very variable. In the
embryo the muscles may contain large quantities, but in the
adult they contain only from 0*4 to 1 per cent.

Inosit (CyH,20^ + 2K,0), or ' muscle-sugar,' which occurs
in minute traces, is non-fermentable, does not rotate polarised
light, and does not reduce Fehling's solution. It does not
belong to the group of carbohydrates at all, being a derivative
of benzene.

Dextrose. It is doubtful whether this is present in fresh
resting muscle.

D. Inorganic constituents. — Muscle contains about 75 per
cent, of water. The ash forms 1 to 1*5 per cent, and consists
chietly of salts of potassium and phosphoric acid. There are
small traces of calcium, magnesium, chlorine, and iron.

Bigor Mortis

All muscles, within a short time of their removal from the
body, or if left in the body after general death, lose their irri-
tability, and this is succeeded by an event which occurs rather
suddenly, and is known as rigor mortis. The muscle, which
was before translucent, supple, extensible, becomes more
opaque, rigid, and inextensible, and shortens. The shortening
is not very powerful, and can be prevented by loading the
muscle moderately Chemical changes also take place. The
muscle, which was previously alkaline, becomes distinctly acid,
the acidity being due to the formation of sarcolactic acid.
There is also pruduction of COj and an evolution of heat.

It is generally believed that this change is identical with
the clotting of muscle-plasma, and that the rigidity as well as

134 PHYSIOLOGY

the contraction of the muscle is due to the coagulation of the
muscle-proteins. That there is at any rate a close connection
between the two sets of phenomena is shown by Brodie's obser-
vations on the heat-contraction of muscle. This observer found
that, if a living muscle be lightly loaded and then warmed very
gradually, a series of stages in the heat-contraction could be
distinguished corresponding to the coagulation temperatures of
the different proteins described by von Fiirth in muscle-plasma.

The onset of rigor is closely connected with the post-mortem
production of sarcolactic acid. If the formation of this acid
be prevented or diminished (as may be effected by keeping
the muscle in an atmosphere of pure oxygen), rigor may
be retarded or prevented altogether. The same result is
obtained if the accumulation of the acid in the muscle is pre-
vented by washing out its blood vessels with a slightly alka-
line normal saline solution. Under these circumstances, the
muscle gradually loses its irritability, and may finally be
regarded as dead, but it will then begin to putrefy without at
any time showing any signs of rigor. The influence of lactic
acid in causing the coagulation of muscle proteins, distinctive
of rigor mortis, is shown by the fact that after severe muscular
fatigue, as in hunted animals, where there has already been a
considerable formation of these waste products of muscular
contraction, rigidity may come on almost immediately after
death. Eigor mortis therefore may be regarded as a
coagulation of muscle proteins induced by the accumulation
of the products of metabolism in the surviving excised
muscle. Of course, a rigidity of muscle may be also brought
about by the direct agency of heat, as by plunging into
boiling water. In this case there has been no time for any
chemical change to take place, and the scalded muscle remains,
like fresh muscle, slightly alkaline to litmus.

A rigid muscle never recovers. It is dead, and in dying
chemical and physical changes have taken place, giving rise
to shortening and rigidity, and converting a fluid complex
substance into an aggregate of insoluble protein, with the
formation of CO.^ and lactic acid. The unstable living molecule
has broken down into dead stable molecules, the potential
energy of the former appearing as heat and work.

The lactic acid formed in nauscle (sarcolactic acid) is a i^hysical isomer of
the lactic acid formed in the fermentation or souring of milk. They both

THE CONTRACTILE TISSUES 135

have the formula CH3.GH(0H).C00H, i.e. they are ethylidene lactic acids.
The lactic acid of fermentation is optically inactive ; sarcolactic acid rotates
polarised light to the right ; while a third isomer which is laevorotatory is
produced by the action of various bacilli and vibriones on cane sugar.

The Gliemical Changes lohich accompany Activity

The principle of the conservation of energy teaches us that
the energy of the contraction of muscle must be derived from
chemical changes, probably processes of decomposition and
oxidation, occurring in the muscle itself. In seeking out the
nature of these changes, three methods are open to us :

1. We can examine the changes in the muscle itself, avoid-
ing so far as possible reintegrative changes by working on
excised muscles.

2. We can investigate the changes in the medium of the
muscle. Muscle may be exposed in a vacuum or in a confined
space of air, and its gaseous interchanges during rest and
activity compared. Or we may lead a current of defibrinated
blood through excised muscles, and determine the change in
the composition of the blood before and after passing through
the muscle under various conditions.

3. A method which, although apparently complex, has
rendered the utmost service to the physiology of muscle, is to
use the changes in the total metabolism of the animal during
rest and muscular work as a clue to the muscular metabolism
itself. In such a case the respiratory exchanges of the animal
are determined (viz. its oxygen intake and its CO., output),
and the urine and faces are carefully analysed, in order to
judge of the action of muscular work on the carbon and
nitrogen metabolism of the body.

By one or other of these methods it has been found that
the main products of muscular activity are the same as those
which are produced during the death of a muscle, viz. sarco-
lactic acid and carbon dioxide.

It was shown long ago by Helmholtz that when a muscle
was tetanised to exhaustion, the total amount of its watery
extractives diminished, while the amount of its alcoholic
extractives increased ; and there is no doubt that part of this
difference is due to the formation of lactic acid. The souring
of muscle during activity can be easily demonstrated by
stimulating the muscle for some time and then crushing a

136 PHYSIOLOGY

fragment of the excised muscle on litmus paper. The litmus
is at once turned red. Or we may inject a solution of acid
fuchsin under the skin of a frog, and the next day expose a
sciatic nerve and stimulate it for fifteen or twenty minutes.
On skinning the hind legs, a difference in colour will be at
once apparent, the leg which has been active being of a deep
rose colour, owing to the action of the acid on the fuchsin.

Sarcolactic acid is not present in a free state in muscle, the acidity being,
like that of urine, due to the presence of acid phosphates. The sarcolactic
acid can be extracted from the muscle by means of alcohol. It is generally
separated in the form of the zinc sarcolactate, by boiling its partially puri-
fied solution with zinc carbonate. Its presence may be tested for by means of
Uffelmann's reagent, which is made by the addition of ferric chloride to dilute
carbolic acid. The purple solution thus produced is at once changed to yellow
by the addition of even traces of lactic acid.

We get a similar formation of lactic acid in excised
mammalian muscles, which are kept alive by an artificial
circulation. We do not know how far the formation of lactic
acid occurs under normal circumstances in the living body.
At all events any lactic acid produced by the muscle during
activity in the normal animal, is further transformed (to CO.,)
before it leaves the body. During severe muscular exercise
however, lactic acid may be formed in the muscles and escape
oxidation in the body, so that it is excreted in the urine.

The second substance, carbon dioxide, is continually being
formed by all living tissues, and is the end-product of
practically all the carbon metabolism of the body. If a
muscle be hung up in a confined space, it will be found to
take up oxygen and give off CO.^ ; and these interchanges are
quickened by causing the muscle to contract.

It is found however that this effect of activity is dependent
on the composition of the gas surrounding the muscle. If it
be hung up in a vacuum or in an atmosphere of nitrogen
or hydrogen, there is a slow evolution of COo, which is not
appreciably quickened during contraction, and seems to be
conditioned by a gradual driving off of CO2 from the alkaline
carbonates in the muscle, as a result of the steady production
of lactic acid which precedes the onset of rigor. If however
the muscle be suspended in an atmosphere of pure oxygen, the
formation of acid is diminished or abolished ; but now each
contraction of the muscle is followed by an increased evolution
of carbon dioxide.

THE CONTRACTILE TISSUES 137

We see therefore that, accordmg to the environment of
the muscle, its activity is attended by the formation either of
lactic acid or of carbon dioxide, the latter substance being the
sole product if sufficient oxygen be supplied to the muscle. If
the supply of oxygen be inadequate, both substances are pro-
duced, the proportion of lactic acid varying according to the
relative inadequacy of the oxygen supply. This relation holds
good both in rest and activity, the effect of activity being
merely to increase the chemical changes which are going on
spontaneously in the surviving resting muscle.

It is an interesting point to determine whether we have
here really two alternative chemical mechanisms for the pro-
duction of energy. We know that sugar can be utilised by
muscle as a food and source of energy. It has been suggested
therefore that, in the absence of oxygen, the energy for con-
traction was derived from a process of disintegration, each
molecule of grape sugar breaking down into two molecules of
lactic acid, thus :

C,H,A=2C3H,303.

Sugar Lactic acid

On the other hand, in the presence of sufficient oxygen, the
sugar would be entirely oxidised with the formation of COo
and water, thus :

C,H, A + 602=6C02 + 6H,0.

Sugar

The change from sugar to lactic acid involves, however,
practically no evolution of energy — so that in the absence of
oxygen the energy of contraction must be derived from some
other source.

It seems more probable that we are dealing here with two
stages of one process, and that in the muscle under normal
conditions {i.e. richly supplied with oxygen) the first chemical
change is one of disintegration, leading to the formation of
lactic acid (and probably other substances), and tliat this is
followed by a process of oxidation, in which all the products of
the first stage are converted into CO., which can be rapidly
eliminated from the muscle. If the supply of oxygen is
deficient, the products of the first stage remain in the muscle,
giving rise to the phenomena of fatigue, and finally inducing

138 PHYSIOLOGY

the coagulation of the muscle proteins which determines rigor
mortis.

We may therefore conceive of the living protoplasm of
the muscle during contraction as using stored-up carbo-
hydrate or allied substances, and oxygen to furnish the
necessary energy ; but it is also possible that the whole living
molecule breaks down with the formation of a still living
protein residue, and waste products such as COo and lactic
acid. Immediately afterwards this living residue takes up
oxygen and carbon-containing substances from the surround-
ing lymph or interstitial substance of the muscle, and is
ready once more to break down and furnish energy in the
process.

A hypothetical muscle molecule of this nature is spoken
of as inogen.

The facts, that the main products of muscular activity are
CO2 and lactic acid, and that no change has been found to
occur in the creatin or other nitrogenous extractives of the
muscle during contraction, have produced a widespread idea
that the sole source of muscular energy is to be sought in
the combustion of carbohydrate or fatty material, the proteins
of the body taking no part in the process. The whole
question will have to be discussed more fully later on, when
dealing with the general metabolism of the body. I may say
here however that, so far as the evidence goes, we cannot
draw any qualitative distinction between the metabolism
which results in muscular work, and the metabolism of the
resting animal. Thus the relative proportion of the CO2
produced to the oxygen taken in, the so-called respiratory

CO

quotient ^ '\ will vary according to the food that is being con-
sumed, being unity with carbohydrates, less than unity with
proteins, and still less with fats. It is found that muscular
work does not alter the respiratory quotient : i.e. during
work the qualitative metabolism of the whole body is the
same as during rest. We must conclude therefore that the
muscle derives its energy from the combustion of all three
classes of foodstuffs, although in the absence of excess of
food, it will perform its work at the expense of stored-up fat
or carbohydrate.

The absence of change in the respiratory quotient during

THE CONTRACTILE TISSUES 139

exercise shows moreover that in a muscle mider normal
conditions the two processes, viz. the taking in of oxygen and
the giving out of CO,,, keep pace one with the other. In
warm-blooded animals, the shutting off of the oxygen supply
rapidly induces paralysis and loss of irritability of the muscles.
This fact, coupled with the fact that, as mentioned above, the
final results of muscular activity differ according as the
muscle is or is not supplied with oxygen, suggests that the
oxygen takes part in the process of activity only at a late
stage, after the disintegration of the complex living molecule
has already begun.

Such a conclusion is, liowever, opposed to the generally accepted views on
the nature of the oxidation processes in the cell. According to Hermann,
Pfliiger, Verworn and others, there is during rest a building up both of oxygen
and food material into the living molecule. Activity consists in a rearrange-
ment of the molecule, with the assumption of more stable positions by the
oxygen and carbon atoms, and a consequent production of C0._, (Cp. the
explosion of gun-cotton or nitroglycerin). The presence of this intramolecular
oxygen in an unstable position would be a necessary condition both for the
irritability as well as for the activity of all forms of living tissue, especially
muscle and nerve.

If the muscle can use all classes of foodstuffs in its meta-
bolism, one would expect to find some change in the nitro-
genous constituents as the result of activity. Physiologists
have searched in vain however for any evidence of the
formation of creatin or urea in excised muscle during con-
traction. Schondorft" has recently shown that if excised
muscle be kept alive by perfusion of defibrinated blood, its
activity is associated with increased formation of ammonia.
The formation of ammonia is however the natural mode of
protection of the whole organism against acid poisoning, and
it seems quite probable that in Schondorff's experiments the
ammonia formation was simply a secondary result of the lactic
acid formation, and not a direct expression of the metabolism
of the active muscle.

140 PHYSIOLOGY

Section 7

CONDITIONS MODIFYING THE lERITABILITY AND

CONTEACTION OP MUSGULAE TISSUE

Temperature

Speaking generally, the effect of warming a muscle is to
quicken all its processes. The latent period becomes shorter
and the muscle curve steeper and shorter.

It is very often observed that the height of contraction of tlie warmed muscle
is greater than tliat obtained at ordinary temperatures. It seems that this
apparent increase in height is really instrumental in origin, the quicker-moving
muscle jerking the lever beyond the real extent of the contraction. If proper
means are taken to eliminate this overshooting of the lever, it is found that the
height of contraction is unaltered between 5° and 20^ C, the only change being
in the time-relations of the curves.

If a muscle be heated gradually (without stimulation) up
to about 45° C., it begins to contract slowly at about 34° C.,
and this contraction reaches its maximum at 45° C., at which
point the muscle has entered into pronounced rigor mortis.

Cold has the reverse effect. The intra-molecular processes
which lie at the root of the muscular activity are slowed, so
that the latent period as well as the contraction period is
prolonged. Curiously the action of cold on the excitability of
muscle is to increase it, so that any form of stimulus is more
effective at 5° C. than at 25° C. Moreover, when maximal
stimuli are being used, and the muscle is heavily loaded, the
first effect of the application of cold may be to increase the
height as well as the duration of contraction, for the same
reason that a gentle prolonged push is more efficacious in
closing a door than would be a heavy blow with a hammer.

If however a muscle be cooled for a short time to zero
or a little below, it loses its irritability, which returns if the
muscle be gradually warmed again.

Prolonged exposure to severe cold, sufficient to cause the
formation of ice in the muscle fibres, irrevocably destroys its
irritability. Warming the muscle now will simply bring about
rigor mortis.

THE CONTRACTILE TISSUES 141

Fatigue

A muscle will not go on contracting indefinitely. If it be
repeatedly stimulated, changes soon become apparent in the
curve of contraction. The latent period is prolonged, as well
as the length of the contractions ; the absolute height and
work done are diminished. At the same time the muscle
does not return to its original length ; the shortening which
remains is spoken of as 'contraction remainder.''

After an initial rise during the first few contractions,
these diminish uniformly in height till they are no longer
apparent, so that the muscle is now said to have lost its
irritability,

Fic;. r,2.

Muscle curves showing fatigue in consequence of repeated stimula-
tion. The first six contractions are numbered, and show the
initial increase of the first three contractions. (Brodie.)

At the same time there is a great prolongation of the
curve, occasioned almost entirely by a retardation of the
relaxation, so that after forty or fifty contractions several
seconds may elapse before the lever returns to the base line.

The fact that the relaxation part of the muscle citrve is affected by various
conditions, especially fatigue, apparently independently of the contraction part,
led Fick to put forward a theory that two distinct processes were concerned in
the response of a muscle to excitation, one process causing the active shortening
and the other the relaxation. (It must be noted that this is not the same as
saying that the lengthening is an active process, a statement negatived by the
behaviour of a muscle when caused to contract on mercury.) He suggested that
the disintegration associated with activity might be conceived as occurring in two
stages : the first resulting in the production of sarcolactic acid and the active
shortening of the muscle ; the second in the further conversion of the acid into

142 PHYSIOLOaY

CO.,, with a consequent relaxation. A retardation of this second pliase would
cause the prolonged curve with ' contraction remainder ' observed in a fatigued
muscle. The absence of any appreciable evolution in the conversion of glucose
to lactic acid, shows however that the formation of lactic acid cannot repre-
sent the whole of the chemical changes involved in the phase of shortening.

If left to itself, the muscle which has been exhausted by
repeated stimulation will recover. The recovery is hastened
by passing a stream of blood, or even of salt solution, through
the blood-vessels of the muscle. Recovery however in a
muscle outside the body is never complete.

The phenomena of fatigue prol)ably depend on two
factors :

(1) The consumption of the contractile material or the
substances available for the supply of potential energy to this
material.

(2) The accumulation of waste products of contraction.
Of these waste products the lactic acid is of great import-
ance. Fatigue may be artificially induced in a muscle by
' feeding ' it with a dilute solution of lactic acid, and this
again removed by washing out the muscle with normal saline
solution containing a small percentage of alkali. After a
certain time the mere removal of waste products by means
of an artificial circulation of salt solution becomes inadequate
to restore contractile power to the muscle. In this case the
muscle can be made to contract once more by supplying it
with fresh food material, as by the circulation of serum or
diluted blood.

The Action of Drugs upon Vohintary Muscle

Of the drugs that have a direct action on muscle, the
most remarkable is veratrin, which causes an excessive pro-
longation of a muscular contraction (produced by a single
stimulus) . Thus the ' twitch ' of a muscle poisoned with
veratrin may last fifty or sixty seconds, instead of the normal
one-tenth of a second (Fig. 63).

Barium salts have a similar though less marked effect.

In order to carry out the poisoning with veratrin, very
weak solutions (1 in 100,000 or 1 in 1,000,000 of normal
saline) should be used and the muscle exposed to its action
for some hours. We get then on a single stimulus a resj)onse
lasting many seconds and exactly similar in height and form to

THE CONTRACTILE TISSUES

143

a tetanus obtained by discontinuous stimulation. If stronger
solutions be used, the action of the drug is apt to affect the
fibres unequally, so that we may have a sharp normal twitch
preceding the prolonged contraction (Fig. 64). If the muscle

Fi<;. (33.

A. Tracing of the contraction of a frog's sartorius, poisoned with

veratrin, in response to a momentary stimulus. The time-
marking indicates seconds.

B. Tetanic contraction of normal sartorius in response to rapidly

interrupted stimuli. (The duration of the stimulus is indi-
cated by the words ' on ' and ' off.') It will be noticed that
the two curves are practically identical. (Miss Buchanan.)

be excited immediately after the prolonged contraction has
passed away, it responds with a single twitch like a normal
muscle, but if allowed to rest a few minutes, stimulation is
again followed by the peculiar long drawn out contraction.

Fig. 64.

Excitation.
'uvj"^\A.<.vla7\jLv_«-^^_/lA-/u>_ajlA_aji.aj' Seconds.

Tracing of the contraction of a muscle poisoned by the injection of
a strong solution of veratrin, showing the double contraction due
to unequal poisoning of different fibres. (Biedermann.)

The action of sodium salts on muscle is of considerable
interest. We are accustomed to use a 0*6 per cent, solution
of NaCl as a ' normal fluid ' to keep muscle preparations

144 PHYSIOLOGY

moist. If however the solution be made with distilled water,
it has a distinctly excitatory effect upon the muscle, so that
single induction shocks may cause tetaniform contractions.
The same excitatory effect is still better marked with solutions
of Na.^CO., (Fig. 65). If a thin muscle, such as a frog's sar-
torius, be immersed in a solution containing 0*5 per cent. NaCl,
0*2 per cent. Na.^HPO^, and 0-04 per cent. Na^COg (Biedermann's
fluid), the muscle enters into a series of frequent contractions,
so that it may wriggle from side to side, or may even ' beat '
for a time with the regularity of heart muscle, though at a
much greater rate.

This excitatory action of sodium salts is neutralised by the
addition of traces of calcium salts. Hence the normal saline
used in the laboratory should always be made with tap water,
containing calcium salts.

Potassium salts, although forming so important a con-
stituent of the ash of muscle, act as muscle poisons, quickly
and permanently destroying its irritability. If a muscle be
transfused with normal fluids containing minute traces of
potassium salts, it at once shows all the signs of fatigue,
signs which may be removed by washing out the potassium
salts by means of 0-6 per cent. NaCl solution. It is possible
that the setting free of potassium salts may be one of the
factors involved in the development of the normal fatigue of
muscle.

THE CONTEACTILE TISSUES 145

Section 8
VOLUNTARY CONTEACTION

In the light of our knowledge gamed chiefly by electrical
excitation of muscles, we have now to inquire into the nature
of ordinary voluntary contraction as it occurs in the muscles
in the body.

The fact that it is difficult to get an artificial prolonged
contraction in excised muscles except by repeated stimula-
tion— that is, by summation of single twitches to form a
tetanus — has led us to view almost every voluntary contraction
as a tetanus. What further evidence is there for this view ?

Muscle- sound. — If we place the end of a stethoscope over
the biceps muscle, and listen while we voluntarily contract the
muscle, a low sound is heard. This is the muscle-sound, and
invariably accompanies any voluntary contraction. Its tone
corresponds to about thirty-six vibrations a second, and it
was thought to be the first overtone of a note of eighteen
vibrations per second, which therefore was looked upon as the
rhythm of ' voluntary tetanus.'

But one hears exactly the same note when listening to
any irregular sound of low intensity. The roar of London
that we hear in the middle of Hyde Park has the same
pitch as the muscle-sound of our contracting biceps. And
really this muscle-sound proves nothing about the number of
contractions composing voluntary tetanus, for it is the natural
resonance-tone of the ear, and therefore selected and inten-
sified in the ear when we listen to any irregular mixture of
tones and noises.

Tracings of most voluntary contractions show superficial
vibrations of eight to twelve a second, and this rhythm is
seen in many movements, such as the clonic convulsions of
epilepsy, and some diseases of the spinal cord. This irregu-
larity would quite well account for the muscle-sound.

But we can get tracings of natural contractions showing
eight or ten complete twitches in the second (contraction and
relaxation), or a continued contraction with eight or ten
superficial waves.

10

146 PHYSIOLOGY

So it is not sufficient to say that voluntary contraction is
a tetanus of eight or twelve per second. If it is a tetanus,
there must be some means by which each individual contrac-
tion can be shortened till it is distinct, or lengthened till
it fuses with the next contraction to produce an unbroken
tetanus. And we must remember that the electrical stimulus
differs in many of its effects from the natural stimulus, and
so not transfer all our results of electrical stimulation too
unreservedly to the contraction of muscles in the living body
in response to the will.

We have in fact definite evidence that discontinuity is not
essential for the production of prolonged contraction. Thus
we have already seen that, during the passage of a constant
current through muscle, there is a continuous contraction in

Fig. 65.

/V/lA/wtwA^.

Continued contraction followed by rhythmic contractions of a
muscle in response to a constant stimulus (Biedermann). The
muscle was excited by the ^lassage of a constant current, the
kathodal end having been moistened with a weak solution of
Na,CO,.

the neighbourhood of the kathode. If the irritability of the
muscle at this point be increased by the application of a
solution of sodium carbonate, this excitation is propagated to
the rest of the muscle and we get a prolonged contraction on
closure of the current, followed by rhythmic contractions
(Fig. 65).

Moreover in excitable frogs (frogs which have been kept
at about 2° or 3° C. for some days) the closure of a descend-
ing current through the nerve causes continued contraction
of the muscle, and in the same way there may be a prolonged
contraction at the opening of an ascending current through
the nerve.

Attempts have been made to decide the question by
recording the electrical changes accompanying the natural

THE CONTEACTILE TISSUES

147

contractions of a muscle, i.e. those excited reflexly through
the central nervous system. It was long ago shown by
Loven that a certain discontinuity could be seen in records
of such changes, as of the mechanical changes ; but a
renewed investigation of the* sul)ject by Burdon- Sanderson

Fk;. m.

Electrometer records of the electrical variations of frog's muscle
under different conditions (Burdon-Sanderson). a, excited by
induction-shocks 14 times per second ; i;, excited for periods of
i sec. by rapidly repeated induction-shocks (60 per second) alter-
nating with equal periods of rest ; c, strychnine spasm (' natural '
contraction).

has proved conclusively that this discontinuity is so to speak
an accident, and an expression of the tendency of the spinal
cord to vhythmic activity. If the electrical changes of a
strychnine spasm l)e photographed by means of the capillary
electrometer, it will be seen that each individual spasm or
twitch is not a simple muscle twitch, but a prolonged con-

148 PHYSIOLOGY

traction similar to a short tetanus. This is well shown in the
accompanying photographs (Fig. 66, c). The period elapsing
between the beginning and the culminating point of the
electrical change of a single twitch is about tx/Vo of a second
(Figs. 59 and 66, a). In the spasms making up the reflex
(natural) contraction, the duration of the electrical change
is more than yfifo of a second (Fig. 66, c). The second
photograph (Fig. 66, b) shows how we may imitate such a
series of changes, not by a series of single stimuli, but by
tetanising for a succession of periods of 0*2 second alternated
with equal periods of rest.

It seems therefore highly probable that the normal reflex
or voluntary contraction is not a tetanus (a condition which
is a product of the physiological laboratory), but a prolonged
single contraction caused by a constant stimulus arriving at
the muscle from the central nervous system.

THE CONTRACTILE TISSUES 149

Section 9
OTHER FORMS OF CONTRACTILE TISSUE

Smooth or Unstriated Muscle

The little we know about the physiology of unstriated
muscle is derived chiefly from experiments on the intestine,
ureter, l)ladder, and retractor penis.' This tissue ditiers from
voluntary muscle in containing numerous plexuses of nerve -
fibres (non-medullated) and ganglion-cells, so that in all our
researches it is difficult to be certain whether the results are
due to the muscle-fibres themselves, or to the nerves and
nerve-cells which are so intimately connected with them ;
especially as we have as yet no convenient drug like curare,
by aid of which we might discriminate between action on
muscle and action on nerve.

The differences between unstriated and voluntary muscle,
although at first sight very pronounced, on further investiga-
tion prove to be in most cases differences of degree only ;
qualities and reactions which are marked in involuntary
muscle being also present in a minor degree in the more
highly differentiated tissue.

The contraction of smooth muscle is so sluggish that the
various stages of latent period, shortening, and relaxation can
be easily followed with the eye. The latent period may be
from 0*2 to 0*8 second, and the contraction may last from
half to three minutes.

In consequence of this lack of differentiation, the smooth
muscle preserves many of the properties of undifferentiated
protoplasm, especially an automatic power of contraction,

' The retractor penis, which is found in the dog, cat, horse, hedgehog (but
not in rabbit or man), is a thin band of longitudinally arranged unstriated
muscle, which is inserted at the attachment of the prepuce, and is continued back-
wards in a sheath of connective tissue to the bulb, where it divides into two
slips which pass on either side of the anus. It is innervated from two sources,
the motor fibres being derived from the lumbar sjnnpathetic and running to the
muscle in the internal pudic nerve, while the inhibitory fibres run in the pelvic
visceral nerves (nervi erigentes) and are derived from the second and third
sacral nerve-roots.

150 PHYSIOLOGY

which is regulated by the condition of the muscle. Thus
whereas the voluntary muscle is intimately dependent on its
connection with the central nervous system, and in the
absence of this is reduced to a flabby inert tissue, the smooth
muscle isolated from all its nervous connections presents in
many cases rhythmic contractions, and can carry out a
peripheral adaptation to its environment.

These rhythmic contractions are almost invariably ob-
served if the muscular tissue be subjected to a certain amount
of tension, after separation from the central nervous system.
The rhythm of the contractions may vary from one (spleen)
to twelve (small intestine) contractions in the minute.

The stimuli for smooth muscle are essentially the same as
for striated. As we should expect however from the sluggish
response of this kind of contractile tissue, the optimum rate
of change of current which excites is very much slower than
in the case of striated muscle. Thus in many instances a
single induction shock, even if very strong, is powerless to
excite contraction, and the make-induction shock of long
duration and low intensity is always more efficacious than the
short sharp break-induction current. A still better stimulus
is the make or break of a constant current. When the latter
form of stimulation is used, response occurs at the make
sooner than at the break, and, just as in voluntary muscle,
the make excitation starts from the kathode and the break
excitation from the anode.

An apparent exception to this statement is afforded by the behaviour of
certain forms of involuntary muscle. In the intestine, in the skin of worms,
and in many other muscular tubes, the smooth muscle-fibres are arranged in
two definite sheets, one consisting of longitudinal, the other of circular fibres.
If non-polarisable electrodes, connected with a constant source of current, be
applied to the surface of the small intestine, when the current is made there
will be apparently a strong contraction of the circular coat at the anode, which
spreads up and down the intestine, and a linear contraction of the longitudinal
coat at the kathode. The same result is observed in the earthworm and leech.
But careful observation shows in each case that the irregularity is really only
apparent, and that in the immediate neighbourhood of the anode there is
relaxation of both coats, with a contraction of the circular coat on each side,
and that at the kathode there is a contraction of both coats. The accom-
panying diagram (Fig. 67) will serve to show the condition of the circular coat
at each electrode.

As a matter of fact, in consequence of the arrangement of the fibres, we have in
the neighbourhood of the anode a number of places (virtual kathodes) where
the current is leaving the muscle cells to enter inert conducting tissues, and in

THE CONTRACTILE TISSUES

151

the same way there will be in the neighbourhood of the kathode a number of
virtual anodes. Thus if we take the ureter and lead a current through it
while it is slung up in thread loops serving as electrodes, there is contraction of
both coats at the kathode and relaxation of both at the anode. If however the

Fig. 67.

At the kathode k there is a small line of constriction, surrounded
by an area of relaxation. At the anode itself the muscle is re-
laxed, but is strongly contracted on each side of the anode, so
that on rough observation it would be thought that contraction
occurred at the anode itself.

ureter be packed in a pulp of blotting paper moistened with normal saline,
thus allowing the current to leave the contractile tissues anywhere along the
ureter, we get the same aberrant results of stimulation as are obtained with the
intestine.

Snmmation

^Ye have already- seen that if two stimuli be sent into
a voluntary muscle within a short interval of time, there is

Fifi. 68.

Diagram to show the spread of current which occurs when a current
is led through a tube such as the ureter by means of two elec-
trodes applied to its surface. It will be noticed that while + E
is the anode, there are immediately below and around it a number
of kathodes e^, e^,, e^,,, e,,,,, due to the current leaving the muscle
to flow through indift'erent tissues. (Biedermann.)

a summation of effect, the contraction due to the second
stimulus being piled so to speak on the top of the first con-
traction. That a maximal twitch is not as high as a tetanus,
the product of summation of many twitches, is due to the

152

PHYSIOLOGY

fact that the relaxation processes of a muscle begin before
it has time to overcome the inertia of the mass moved, and
so accomplish its maximum shortening. If therefore we
support the muscle in any way, whether by screwing up the
lever (after-loading) or by sending in a previous stimulus, the
contraction due to a stimulus will be more pronounced, until
the shortening of the muscle attains that observed in tetanus.
For the same reason the height of a single twitch in relation
to a tetanus of the same muscle increases as we sloio the
contraction, until, with a prolongation such as is produced by
veratrin, there is no difference at all l)etween the height of
a maximal single contraction and the height of a tetanus
(Fig. G3, p. 143).

Fig. r,9.

Contractions of a frog's muscle. Two single twitches are followed
by a tetanus, which is almost twice as high as a single contrac-
tion. After two more single twitches, the drum was made to
rotate more slowly, and single shocks employed, at the same time
as the ' after-loading ' was continually increased. It can be seen
that the curve obtained in this way is as high as the original
tetanus, (v. Frey.)

These considerations would lead us to expect no trace of
any process analogous to summation of contraction in the
slowly moving smooth muscle. In the heart muscle this is
the case, no increase in the height of a contraction being
produced by sending in one, two, or more shocks in quick
succession. When however we record the contractions of a
muscle, such as the retractor penis, which is more closely
under the control of the nervous system, and excite with a
series of induction shocks, we get results which at first sight
are exactly analogous to the summation of contraction in a
voluntary muscle. It may be noticed however that the first
three or four stimuli are ineffective, and that there is in this
case a summation before any contraction has occurred, a
summation of stimuli. Each stimulus in fact alters the state

THE CONTRACTILE TISSUES 153

of the contractile tissue and makes it more ready to respond
to the next stimulus, so that the stimuli become more and
more effective. If time is allowed for the muscle to relax
between successive stimuli, this summation is evidenced by
a continually increasing height of contraction, the so-called
' staircase.' It will be remembered that the same initial
increase of effect was observed when voluntary muscle was
excited by continually recurring stimuli (v. Fig. 62, p. 141).

We shall meet with other examples of this summation of
stimuli when dealing with the physiology of the central
nervous system. It is indeed a fundamental phenomenon in
the physiology of excitation.

Chemical Stimulation

Strong salt solution excites contractions just as in the case
of skeletal muscle. Many drugs such as physostigmin, ergot,
lead salts, digitalis, may act directly on smooth muscle and
cause contraction. As one would expect however from the
greater independence of the smooth muscle, the action of
these drugs varies from organ to organ, muscle-fibres, which
apparently are histologically identical, reacting diversely
according to their origin.

Mechanical Stimulation

Smooth muscle may react to a local pinch or blow with a
local or a general (propagated) contraction. The most impor-
tant form of mechanical stimulation is that produced by ten-
sion. The effect of increasing the tension on smooth muscle
may be twofold : causing in the first place relaxation and in
the second excitation with increased contraction. These two
effects may be illustrated by taking the case of the bladder.
If this viscus (which is surrounded by a complete coat of
smooth muscle) has all its connections with the central nervous
system severed, it is when empty in a state of tonic contraction.
If fluid be injected into it rapidly there is a great rise of
pressure in its cavity, due to the forcible distension. If how-
ever the fluid be injected slowly the bladder muscle relaxes to
make room for it, so that a considerable amount of fluid may
be accommodated in the bladder without any great rise of

154 PHYSIOLOGY

pressure. This process of relaxation has however its limit.
If the injection of fluid be continued, the walls begin to be
stretched passively, and this increased tension acts as a
stimulus causing marked rhythmic contractions of the whole
bladder.

In the same way the response of a smooth muscle to an
electrical stimulus is much increased by previous increase of
the tension on the muscle-fibres.

Proi^agation of the Excitatory State, or Wave of
Contraction

In the case of voluntary muscle we have seen that, on
stimulating any part of a muscle-fibre, a wave of contraction
is started which travels to each end of the fibre, but no further.
There is no propagation from muscle-fibre to muscle-fibre, the
synchronous contraction of the whole muscle being brought

Fig. 70.

about by simultaneous excitation of all its fibres. This isola-
tion of the excitatory state is not found in smooth muscle. A
stimulus applied to any part of a sheet of smooth fibres may
travel all over the sheet just as if it were a single fibre. It
seems probable indeed that there is protoplasmic continuity
by means of fine bridge-like processes between adjacent muscle-
cells. And even in the absence of such bridges, the propaga-
tion of the contraction could be easily accounted for. Although
in the case of voluntary muscle the rule is isolated contraction,
yet a very small change in the muscle, such as is produced
by partial drying or by pressure, is sufficient to cause the
contraction to spread from one fibre to another. Indeed by
clamping two curarised sartorius muscles together, as in the
diagram (Fig. 70), it is found that stimulation of the muscle
A causes contraction of the muscle b. The current of action
of A in this case has served to excite a contraction in b.

THE CONTRACTILE TISSUES 155

It must be remembered that in all nnstriated muscle the fibres are sur-
rounded by a network of non-medullated nerve-fibres. Some physiologists
are inclined to ascribe to these fibres an important part in the propagation
of the contraction wave. In the case of the heart muscle however, it can
be shown almost conclusively that the propagation takes place indepen-
dently of nerve-fibres, and probably the same is true for certain involuntary
muscles.

Infiience of Temjyei'atttre

Smooth muscle is extremely susceptible to changes of
temperature ; we may say as a rule that warming causes
relaxation, while application of cold causes a tonic contraction.
The condition of the muscle at any given time does not depend
only on its actual temperature but also on the rapidity with
which this temperature has been reached. Thus a rapid
cooling of the retractor penis muscle of a dog from 35° to 25°
may cause a contraction as extensive as would be produced
by a slow cooling to 5° C. On warming a muscle from 30° to
50° C. it lengthens gradually up to about 40°, and it may then
undergo a marked heat contraction (varying in degree in
different muscles) at about 50"^ C. which may pass off at a
somewhat higher temperature. It is killed somewhere between
40° and 50° C. It seems very doubtful whether any true
rigor mortis occurs in smooth muscle. The hard contracted
appearance of the smooth muscle in a recently dead animal
is chiefly conditioned by the fall of temperature. On excising
the muscle and warming it up again to body temperature, it
may again relax and show signs of irritability two or three
days after the death of the animal. Different smooth muscles
however vai\v very much in their tenacity of life.

Double Innervation

We have seen that voluntary muscle is absolutely depen-
dent for its activity on the central nervous system. Cut oft"
from this it is flabby and motionless. Its sole function is to
contract efiliciently and smartly on receipt of impulses arriving
along its nerve. It is only necessary therefore that these
impulses should be of one character — motor, and we know
that each fibre of a muscle, such as the sartorius, receives one
efferent nerve-fibre terminating in an end-plate.

In the case of smooth muscle however we have a tissue

156

PHYSIOLOGY

which has an activity and reactive power of its own, and apart
from its innervation may be at one time in a state of relaxation,
at another in a state of tonic contraction. In order therefore
that the central nervous system should have efficient control
over such a tissue, it must be able to influence it in two direc-
tions : it must be able to induce a contraction or increase a
contraction already present, and it must also be able to put
an end to a spontaneous contraction, i.e. to induce relaxation.
In order to carry out these two effects, smooth muscle receives
nerve-fibres of two kinds from the central nervous system,
one kind motor, analogous to the motor nerves of skeletal

Fig 71.

Tracing from the retractor penis muscle of the dog, showing length-
ening (inhibition) on stimulation of the nervus erigens, and a
smart contraction on stimulating the pudic (motor) nerve. (Move-
ments of muscle reduced J.)

muscle, the other kind inhibitory, causing relaxation or cessa-
tion of a previous contraction. All these fibres belong to the
visceral or * autonomic ' system. They are connected with
ganglion-cells in their course outside the central nervous
system, and their ultimate ramifications in the muscle are
always non-medullated. A typical tracing of the opposite
effects of these two sets of nerves is given in Fig. 71.

In the invertebrata many ' voluntary ' striated muscles probably possess
a double innervation. Thus in the crayfish, the adductor muscle of the claw
consists of striated muscular fibres, every fibre of which is supplied with
two kinds of nerve-fibres. By exciting these fibres one may get, according to
the conditions of the experiment, either contraction of a relaxed muscle or
relaxation of a tonically contracted muscle (Fig. 72).

THE CONTEACTLLE TISSUES 157

Amceboid Movement

We have already described amceboid movement as seen
in the amoeba and the white blood-corpuscles. It only
remains to enumerate the chief factors that influence its
activity.

Amoeboid movements can occur only within certain limits
of temperature (about 0'' C. to 40°) ; within these limits it is
the more active the higher the temperature. At about 45°
the cell goes into a condition resembling heat rigor.

The fluid in which the corpuscles are suspended is of
great importance. Distilled water, almost all salts, acids

Fig. 72.

Tracing of contraction of adductor muscle of claw of crayfish,
showing inhibition resulting from stimulation of its nerve
(at b) by means of a constant current. The break of the
current causes a second smaller inhibition. (Biedermann.)

and alkalies, if strong enough, stop the action and kill the
cell.

The movements are also stopped by CO^ or by absence of
oxygen.

Artificial excitation, whether electrical, chemical, or ther-
mal, causes universal contraction of the corpuscle, which
therefore assumes the spherical form.

Ciliary Movement

Cilia are met with in man in nearly the whole of the
respiratoi^Y passages and the cavities opening into them, in
the generative organs, in the uterus and Fallopian tubes of
the female, and the epididymis of the male, and on the
ependyma of the central canal of the spinal cord and its
continuation into the cerebral ventricles.

158

PHYSIOLOGY

The cilia (Fig. 78) are delicate tapering filaments which
project from the hyaline border of the epithelial cells. There
are about twenty or thirty to each cell. The hyaline border
is really made up of the enlarged basal portions of the cilia.

In action the cilia bend suddenly down into a hook or
sickle form, and then return more slowly to the erect position.
This movement is repeated many (twelve to twenty) times
a second, and thus serves to move forward mucus, dust, or
an ovum, as the case may be. The movement seems to be
entirely automatic, and it is quite unaffected by nerves, at
any rate in all the higher animals.

Fig. 73.

Ciliated columnar epithelium from the trachea of a rabbit :
]ii\ m', vi', mucus-secreting cells. (Schafer.)

There is however a functional connection between all the
cells of a ciliated epithelial surface, so that movement of
the cilia, started in one cell, spreads forward as a wave, just
as, when the wind blows, waves of bending pass over a field
of corn.

The conditions of ciliary action are exactly the same as
those for amoeboid movement of naked cells.

The minuteness of the object has, up to now, prevented
us from deciding whether the cilium is itself .actively con-
tractile, or whether it is simply passively moved by the
action of the basal part situated in the hyaline border of the
cell.

159

CHAPTER V

NERVE-FIBRES (CONDUCTING TISSUES)

Section 1
GENEEAL PEOPEETIES OP NEEVE-FIBEES

In the last chapter we studied incidentally some of the
functions of nerve-fibres. We found that, when we stimu-
lated the nerve of a nerve-muscle preparation at any part
by electrical, thermal, or mechanical means, the stimulus was
followed, after a very short interval, by a contraction of the
muscle. This observation illustrates the two functions of
nerve-fibres, irritability and conductivity, — that is to say,
a suitable stimulus can set up changes in any part of the
nerve, which are transmitted down the nerve without any
visible eliects occurring in it ; and it is not until this nervous
change has reached the muscle that a visible effect takes
place in the shape of a contraction. Now in the human
body a direct excitation of the nerve-fibre in its course never
takes place under normal circumstances. The only function
the nerve-fibre has to perform is that of conducting impulses
from the sense organs at the periphery to the central
nervous system, and efferent impulses from this to the
muscles and others of its servants. Hence it is absolutely
essential that there should be vital continuity along the whole
length of the fibre. Damage to any part of it, such as by
crushing, heat, or any other injurious condition, infallibly
causes a block to any impulse.

It was pointed out in the introductory chapter that a
nerve-fibre is essentially a long process or arm of a nerve-
cell. The cells may either be situated on the surface of the
body or, as in most cases in the higher animals, they may be
withdrawn from the surface to form special collections of
cells such as the posterior root ganglia, or a whole mass of

160

PHYSIOLOGY

cells and interlacing processes making up a central nervous
system. Although all nerves are alike in possessing as their
conducting part the continuous strand of protoplasm produced
from the nerve-cell, they develop in the course of growth
certain histological differences, which appear to bear some
relation to the nature of the processes they conduct or to the
character of their parent-cell. Thus all the fibres which are
given off from and which enter the central nervous system,
i.e. the brain and spinal cord, belong to the class known as
medullated. In this type the conducting core or axis -cylinder

Fig. 74.

Three meduUitteJ and two nuu-medullated nerve-fibres ; n, node
of Ranvier (from Yeo).

is surrounded with a layer of apparently insulating material
known as myelin, forming the medullary sheath, or the sheath
of Schwann. This sheath consists of a fatty material com-
posed largely of lecithin, and staining black with osmic acid,
supported apparently in the interstices of a network formed
of a horny substance known as neurokeratin. The medul-
lary sheath is surrounded by a structureless membrane, the
primitive sheath or neurilemma. At regular intervals a break
occurs in the medullary sheath, the neurilemma coming in
close contact with the axis- cylinder. This break is the node
of Ranvier, the intervening portions of medullated nerve being
the internodes. In each internode, lying closely under the
neurilemma, is an oval nucleus embedded in a little granular
protoplasm. The medullated nerve-fibres vary considerably

NERVE-FIBKES (CONDUCTING TISSUES) 161

in diameter, the largest fibres being distributed to the muscles
and skin, the smallest carrying impulses from the central
nervous system to the viscera. The latter class all come to
an end in some collection of ganglion cells of the sympathetic
chain or peripheral ganglia, the impulses being carried on
to their destination by a fresh relay of non-meduUated nerve-
fibres.

The non-medullated fibres differ from the medullated
simply in the absence of a medullary sheath. They possess,
in many cases at any rate, a primitive sheath, under which we
find nuclei lying closely on the side of the fibre and bulging
out the sheath. In their ultimate ramifications they tend to
form close networks or plexuses and appear to lose the last
traces of a sheath.

The medullated nerves are bound together by connective
tissue (endoneurium) into small bundles, which are again
united by tougher connective tissue into larger nerve-trunks.
These fibres as a rule branch only when in close proximity to
their destination, and then the branching always occurs at
a node of Ranvier.

11

162

PHYSIOLOGY

Section 2
PROPx\GATION ALONG NERVE-FIBRES

The velocity of propagation along a nerve-fibre may be
measured, although in early times it was thought to be as
instantaneous as the lightning flash. To measure the velocity
of propagation in a motor nerve, a frog's gastrocnemius is
prepared, Avith a long piece of sciatic nerve attached. The
muscle is arranged (Fig. 75) so that its contraction may be

Fig. 75.

Diagram of arrangement of experiment for the determination of the
velocity of transmission of a motor impulse down a nerve. The
battery current passes through the primary coil of the inductorium
C, and a ' kick over ' key k. By means of the switch S, the break
shock in the secondary circuit can be sent through the nerve n, either
at b, or at a. The muscle in is arranged to write on the blackened
surface of a trigger or pendulum myograph, and is excited during
the passage of the recording surface by the automatic opening of
the key h. (The time-marker is not shown.)

recorded on a rapidly moving surface, on which are also re-
corded, by means of electro-magnetic signals, the moment at
which the stimulus is sent into the nerve, and also a time-
marking showing 2-^ sec. Tracings are now taken of the
contraction of the muscle : first, when the nerve is stimulated
at its extreme upper end ; secondly, as close as possible to
the muscle. It will be found that the latent period, which
elapses between the point at which the stimulus is sent into
the nerve and the point at which the lever begins to rise, is
rather longer in the first case than in the second. The
difference in the two latent periods gives the time that it has

NERVE-FIBEES (CONDUCTING TISSUES) 163

taken for the nervous impulse to travel down the length of
nerve between the two stimulated points. Calculated in this
way, the velocity of propagation in frog's nerve is about 28
metres per second.

The velocity of propagation in sensory nerves is more
difficult to determine, owing to the fact that a sensory impulse,
on arrival at the receiving organ — i.e. some part of the central
nervous system — does not at once give rise to some definite
recordable mechanical change, such as a muscular contraction.
There is another method of determining the velocity of conduc-
tion, which may be used also with sensory fibres. The pas-
sage of a nerve-impulse down a nerve, just as the passage of
a wave of contraction along a muscle-fibre, is immediatel}'
preceded or accompanied by an electrical change, which also
travels along the nerve as a wave of ' negativity.' The velocity
of propagation of this wave may be measured, and is found
to give the same numbers as the velocity determined by the
preceding method.

The existence of this electrical change enables us to show
that a nerve-impulse, excited at any point in the course of a
nerve-fibre, travels in both dircctiuns along the fibre. The
power of nerves to transmit impulses in either direction is
shown further by the experiment known as Kiihne's gracilis
experiment. The gracilis muscle of the frog is separated into
two portions by a tendinous intersection, so that there is no
muscular continuity between the two halves. The nerve to the
muscle divides into two branches, one to each half, and at
the point of junction there is diuisLO)i uf the axis-cylinders
themselves. It is found that if the section a in the diagram
(Fig. 76), which is quite isolated from the rest of the muscle,
be stimulated, as by snipping it with scissors, the whole
muscle contracts. If however the portion of the muscle which
is free from nerve-fibres be stimulated in the same way, the
contraction is limited to the fibres directly stimulated, show-
ing that in the first case the stimulus excited nerve -fibres
which transmitted the impulse iqj the nerve to the point of
division and then down again to the other half of the muscle.
Since nerves have this power of conduction in ])oth directions,
it might be thought that a single set of nerve-fibres might
very well subserve both afferent and efl:erent functions, at
one time conducting sensory impulses fi-om periphery to cord,

164

PHYSIOLOGY

at another time motor impulses from cord to muscles. But
this is not the case. As a matter of fact we find in the body
a marked differentiation of function between various nerve-
fibres.

We have already mentioned the division of nerves into
afferent and efferent, and we find further that each of these
afferent or eiferent fibres has its own proper impulses to con-
duct, and conducts only these impulses. Thus some fibres in
the anterior spinal roots conduct ordinary motor impulses to
muscles, others impulses causing contraction or relaxation
of the muscular walls of arteries, or which quicken or slow

Fig. 76.

Kiihne's gracilis experiment.

the contractions of the heart. We shall return to this ques-
tion of restricted function of nerve-fibres under the heading
of * Miiller's law of specific irritability ' when we come to treat
of the special senses.

The rate of propagation of a nervous impulse is quickened
by heat (up to about 38° C.) and slowed by cold. At a little
over 0" C. the rate in frog's nerve is only about one metre per
second.

Events accompanying the Passage oj a Nervous Impidse

In muscle we saw that the passage of an excitatory wave
was accompanied or followed by electrical changes, production
of heat, and mechanical change, all pointing to an evolution

NERVE-FIBRES (CONDUCTING TISSUES) 165

of energy from the explosive breaking down of contractile
material.

In nerve however, which serves merely as a conducting
medium, we should not expect so much expenditure of energy,
or in fact any expenditure at all. All that is necessary is
that each section of the nerve should transmit to the next
section just so much kinetic energy as it has received from
the section above it. And experiment bears out this con-
clusion. The most refined methods have failed to detect the
slightest development of heat in a nerve during the passage of
an excitatory process ; and we know already that there is no
mechanical change in the nerve. The only physical change
in a nerve under these circumstances is the development of
a current of action. A nerve becomes, when excited at any
point, negative at this point to all other parts of the nerve,
and, just as in muscle, this 'negativity' is propagated in the
form of a wave in both directions along the nerve.

That the excitatory process in nerves is probably accom-
panied by certain small chemical changes is indicated by the
facts that, in the complete absence of oxj^gen, the nerve fibres
lose their irritability, and that this loss of irritability is
hastened by repeated stimulation of the nerve. When the
irritability has been abolished by stimulation in the absence
of oxygen, it may be restored within a few minutes by re-
administration of oxygen to the nerve.

If we connect a galvanometer to two points of an uninjured
nerve, no current is observed, all points of a living nerve at
rest being iso-electric. On making a cross-section of the
nerve at one leading-off point, a current is at once set up,
which passes from the surface through the galvanometer to
the cross-section. This is a demarcation current, set up at
the junction between living and dying nerve. It will be
noticed that this current rapidly diminishes in strength and
finally disappears, owing partly to the fact that the dying pro-
cess started in the nerve by the section extends only as far as
the next node of Ranvier and there ceases, so that after a
short time the electrode applied to the cross-section is simply
leading off an intact living axis-cylinder through the dead
portion of the nerve, which acts as an ordinary moist con-
ductor. On making a fresh section just above the previous
one, the process of dying is again set up, and the demarcation

166 PHYSIOLOGY

cuiTent is restored to its original strength. If, while the
demarcation current is at its height, we stimulate the other
end of the nerve with an interrupted current, the needle of
the galvanometer swings back towards zero, i.e. there is a
negative variation of the resting current.

In order to demonstrate the wave-like progression of the
electrical change from the excited spot along the nerve, it ia
necessary, as in the case of muscle, to make use of the repeat-
ing rheotome or of a very sensitive capillary electrometer. It
is then found that the change progresses along the nerve at
the same rate as the nervous impulse, i.e. twenty-eight to
thirty-three metres per second. But it lasts only an extremely
short interval of time at each spot, viz. six to eight ten-thou-
sandths of a second. Thus the length of the excitatory wave
in nerve is about 18 mm.

NERVE-FIBRES (CONDUCTING TISSUES) 167

Section 3
EXCITATION OF NERVES

We must now study more fully the changes which take
place in a nerve during the passage of a current through it,
and the manner in which these changes are ahle to generate a
nervous impulse. Under normal circumstances, if a constant
current he passed through the nerve of a nerve-muscle pre-
paration for a short time, the muscle responds only at the
make and the hreak of the current, remaining perfectly
quiescent all the time the current is passing. If the nerve he
in a very excitahle condition, it is possible that the muscle
may be thrown into a tetanus or continued contraction during
the whole time that the current is passing (closing tetanus).
On the other hand, if a strong ascending current be passed
through the nerve for a considerable time, the muscle when
the current is broken may go into continued contraction,
which may last some time. Normally however the muscle
simply responds with a single twitch at the make and break
of the current ; although, on investigating the condition of
the nerve during the passage of the current, we find that it is
considerably modified.

This modification in the condition of the nerve is spoken
of as eJectrotonus, and includes changes in its irritability and
its electrical condition.

To investigate these changes the following apparatus is
necessary : — two constant batteries, induction coil, a reverser
and keys, a pair of non-polarisable electrodes, and a pair of
ordinary platinum electrodes. Fig. 77 represents roughly
the arrangement of the experiment. A constant current
from the battery is led through a part of the nerve by means
of non-polarisable electrodes, which are about one inch apart.
In this circuit we put a reverser, b}^ means of which the
direction of the current of the nerve may be changed at will,
and a key to make or break the current. This is the polaris-
ing cu'cuit. The other battery is arranged in the primary
circuit of the coil, a key being interposed, so that we may use
make or break induction-shocks, which are applied to the

168 PHYSIOLOGY

nerve by means of the small platinum electrodes. The
tendon of the muscle is connected by a thread with a lever,
which is arranged to write on a smoked surface, so that the
height of the contraction can be recorded.

We first find the position of the secondary coil, at which
the break induction-shock is a submaximal stimulus, and we
employ this strength of stimulus throughout the experiment.
The make induction-shock is prevented from acting on the
nerve by closing a short-circuiting key in the circuit of the
secondary coil. The nerve is now stimulated at various
points with a single break induction-shock, and the con-
tractions recorded. The heights of these contractions serve

Arrangement of api^aratus for showing eleetrotonic changes in
irritability, e. Exciting current, p. Polarising circuit, r. Pohl's
reverser.

to indicate the irritability of the nerve at the point stimu-
lated. We now throw the polarising current into the nerve.
At the make of this current the muscle will probably respond
with a twitch which is not recorded. We then test once
more the irritability of different points of the nerve, and we
find that, when the stimulus is applied near (a) the point
where the current enters the nerve (anode), the stimulus,
which before gave a moderately large contraction of the
muscle, now has either no effect or else produces a very
weak contraction. On the other hand, in the region of the
kathode the stimulus, which before was submaximal, has
now become maximal, as is shown by the increase in the
height of the contraction evoked by the induction-shock.

We now reverse the direction of the polarising current,
so that the curx-ent of the nerve runs from (k) to (a). With

NERVE-FIBRES (CONDUCTING TISSUES) 169

this reversal of current there is also a reversal of the changes
in the nerve ; that is to say, the normally submaximal
stimulus is maximal when applied near (a), and minimal
when applied near (k). On break of the polarising current
the condition of the nerve returns to normal, and the sub-
maximal stimulus is once more submaximal throughout.

This return to normal conditions however is not immediate, since the first
effect of breaking tlie current is a swing back, so to speak, past the normal,
the diminished irritabilitj' at the anode giving place to an increased irritability,
which only gradually subsides. In the same way, immediately after the
polarising current has ceased to flow, the neighbourhood of the kathode
acquires a condition of diminished irritability, and this only gradually gives
place to a normal condition.

This experiment teaches us that, when a constant current
is passed through a nerve, there is increase in the irritability
in the nerve near the kathode, and a diminution in irrita-
bility near the anode. These conditions of increased and
diminished irritability are spoken of as katelectrotonus and
anelectrotonus respectively. In the previous chapter we
learnt that a make contraction always starts from the
kathode, and a break contraction from the anode. Now
the event that takes place at the kathode on make and at
the anode on break of a constant current is, as the last
experiment shows us, a rise in irritability, in the former
case from normal to above normal, in the latter from sub-
normal to normal. Hence we may sa}'' that the excitation
is caused by a sudden rise of irritability, which may be due
either to a sudden appearance of katelectrotonus, or a sudden
disappearance of anelectrotonus. I have said sudden, be-
cause the steepness of the rise of irritability is a necessary
factor in causing excitation. If the polarising current passing
through a nerve be slowly and gradually increased to con-
siderable strength, it will give rise to no contraction. The
degree of suddenness of the rise, which is most beneficial
in causing contraction, varies with the nature of the tissue
stimulated. Thus it is more rapid in nerve than in muscle,
and in pale muscle than in red muscle, and in voluntary
muscle than in unstriated muscle.

It is evident that there must be, somewhere between the
anode and kathode, an indifferent point — that is to say, a re-
gion where the irritability is neither increased nor diminished.

170

PHYSIOLOGY

We find experimentally that this indijfferent point is nearer
the anode when the polarising current is weak, and gets
nearer to the kathode as the current is strengtliened, so
that with very strong currents nearly the whole intrapolar

Fir,. 78.

Diagram to show the variations of irritability in a nerve during the
passage of polarising currents of different strengths. The degree
of change is represented by the distance of the curves from the
base line ; the part of the curve below the line signifying den-ease,
that above the line increase of irritability. A, anode; B, kathode;
7/1, effect of weak current ; ?/.„ medium current ; y.^, strong current.
It will be noticed that the indifferent point, ,r, where the curve
crosses the horizontal line, approaches nearer and nearer the
kathode as the current is increased in strength (from Foster, after
Pfiiiger).

length is in a condition of anelectrotonus (Fig. 78). When a
strong polarising current is used, the depression of irritahility
at the anode is so marked that no impulse can pass this
region. Thus if we send a very strong ascending current

Fig. 79.
ascendinq current

kath.

an.

make excitation blocked
at anode.

kath.

break excitation at anode
blocked at kathode.

Diagram to show the blocking effect of a strong constant current
passed through the nerve of a nerve-muscle preparation.

through the nerve, there is no contraction at make. This
is owing to the fact that the impulse started at the kathode
on make of the current cannot reach the muscle, its passage
down the nerve heing hlocked in the region of the anode
(Fig. 79, A).

NERVE-FIBRES (CONDUCTING TISSUES)

171

The results of stimulating motor nerves by means of constant currents
were stuclied by Pfliiger and, embodied in a table, make up what is known as
Pfliiger's law. The result of stimulation varies with the strength of a
current.

Laiv of Contracticm

Strenglib of current.

Ascending.

Descending.

Make. Break.

Make. Break.

Weak ....

0 0

0

Medium

c c

C c

Strong

0 C or T

C or T 0

c = contraction. C = strong contraction. T = tetanus. 0 = no effect.

With the weakest currents, excitation occurs only at make, since a make-
stimulus, i.e. the rise of katelectrotonus, is always more effectual than a break-
stimulus, i.e. the disappearance of anelectrotonus. With currents of moderate
strength, excitation occurs both at make and break, being better marked at
make, especially in the case of descending currents. With very strong currents,
we get a contraction at make only when the current is descending, since, when

Fig. 80.

Arrangement of experiment to demonstrate Pfliiger's law
of contraction.

the current is ascending, the excitation started at the kathode cannot pass the
block at the anode. For the same reason a break contraction is obtained only
with an ascending current, since at the break of a descending current there
is a swing-back of the nerve at the kathode to a condition of diminished
irritability, which effectually blocks the excitation started higher up the nerve
at the anode.

The aiTangement of the experiment for demonstrating Pfliiger's law is
shown in Fig. 80. The strength of the current is graduated by means of the
rheochord, the current being led into the nerve by means of non-polarisable
electrodes. It is extremely important in these experiments to avoid any
injury or drying of the nerves at either of the two electrodes, since the excita-
tory efi'ect either at make or break would be abolished by local injury.

172 PHYSIOLOGY

These results, worked out chiefly on motor nerves, have
been confirmed as far as possible experimentally on sensory
nerves, and on muscle and contractile tissues generally, and
probably hold good for all irritable living tissues.

It is said that an anelectrotonus takes some time to attain
its full height, and a katelectrotonus reaches its maximum
almost directly after the current is made. Hence a current of
very short duration probably excites only at the make, the break
occurring before the anelectrotonus is developed enough for
its disappearance to cause a stimulus. Thus induction-shocks
(both make and break) may be looked upon as make-excitations,
the excitation however being stronger in the case of the break
induction-shock than in that of the make.

Other things being equal, a current of given strength causes
a stronger excitation the greater the length of nerve that
it flows through. It must be remembered however that the
nerve offers considerable resistance to the passage of the
current, and so, to keep the current constant while increasing
the length of intrapolar nerve, we must largely increase the
electromotive force employed.

A very convenient method of showing the effect of the length of intrapolar
nerve on excitation has been suggested by Gotch. The two sciatic nerves of
a frog are dissected out, one of them being in connection with the gastrocnemius.
These are first arranged as in Fig. 81 a (p. 173). a, b, and c are three non-polaris-
able electrodes, the terminals of a constant battery being connected to a and c.
The position of the rider on the rheochord is then ascertained at which make
of the current just excites contraction in the muscle of nerve 2, the current in
this case passing from a to b along nerve 1, and from 6 to c along a small
piece of nerve 2. We will suppose that eleven units of current are necessary
to produce excitation, b is then withdrawn and the nerve 2 laid on a (Fig 81, b).
so that the current can now pass from ft to c entirely through a long stretch
of nerve 2. On again seeking the minimal stimulus, it will be found that a
smaller current is sufficient to excite, contraction being obtained with seven
units. Since the length of nerve traversed, and therefore the resistance to the
current, aie the same in both cases, it is evident that a current is more effective
the greater the length of excited nerve that it traverses.

A nerve cannot be excited by currents passed transversely
across it, since in such cases the anode and kathode lie so
close to one another in a nerve-fibril, as it is traversed by
a current, that their effects counteract one another.

NERVE-FIBRES (CONDUCTING TISSUES)

173

Electrical Stimuli as aiyplied to Human Nerves

When we attempt to apply the results gained on frog's
nerves to man, we are met at once by the difficulty that we
cannot dissect out the nerves and apply stimuli to them directly.
So usually unipolar excitation is used, one electrode, either
anode or kathode, being applied to the nerve to be stimulated,
and the other to some indifferent point, such as the back. It
is evident under these circumstances that the current is con-
centrated as it leaves the anode and reaches the kathode, and

Diagram of anangcment of experiment for investigating the
influence of the intrapolar length of nerve on the excitatory
effect of the current.

diffuses widely in the body, seeking the lines of least resistance.
Thus it is impossible to get pure anodic or kathodic effects.
If the anode be applied over the nerve, the current enters by
a series of points (the polar zone), and leaves by a second
series (the peripolar zone). The polar zone will thus be in the
condition of anelectrotonus, and the peripolar zone in that
of katelectrotonus. The current however will be more con-
centrated at the polar than at the peripolar zone, and so
the former effect will predominate. These restrictions in the

174

PHYSIOLOGY

application of the current cause slight apparent irregularities
in the law of contraction as tested on man.

Other Methods of Stimulation

1, Thermal. If the temperature of a nerve be gradually
raised, no effect is noticed till about 40' C. is reached, when
the muscle may enter into weak quivering contractions.
Sudden warming of the nerve always gives rise to excitation.
At about 45° C. the nerve loses its irritability and dies.

A nerve may be rapidly cooled without any excitation
taking place. At about 0° C. the conductivity of mammalian

Fig. 82.

Electrodes applied to the skin over a nerve-trunk. In a the polar area
is anelectrotonic and the peripolar katelectrotonic. The former
condition therefore preponderates, since the current here is more
concentrated. In b the conditions are reversed, the polar zone
corresponding in this case to the kathode. (Waller.)

nerve-fibres is absolutely abolished, and hence this method of
cooling is of great value when it is required to divide a nerve
physiologically without exciting it.

2. Mechanical. A nerve may be excited by crushing or
cutting. These methods however destroy the nerve. It is
possible to excite a nerve mechanically, without any serious
injury to it, by carefully graduated taps, and this method has
been used in investigating the phenomena of electrotonus.

3. Chemical. All chemical stimuli applied to the nerve

NERVE-FIBRES (CONDUCTING TISSUES)

175

have a speedy effect in destroying its irritability. The che-
mical stimuli most used are strong salt solutions, glycerin, or
weak acids. If any one of these be applied to a motor nerve,
the muscle enters into an irregular tetanus, which lasts till
the irritability of the nerve is destroyed at the part stimulated.
It is thus evident that we are justified in our choice of electrical
stimuli in all ordinary experiments on nerves.

The Energy involved in tlic Excitatiun of a Nerve

We have hitherto only considered electrical stimulation by means of a con-
stant current or an induced current. It is possible however to store up a
certain (juantity of electricity in a condenser and then to excite a nerve by dis-
charging the condenser through it.' The arrangement of such an experiment
is shown in Fig. 83. By means of the switch S, the condenser can be put into

Fig. 83.

Arrangement of apparatus for the excitation of a nerve by means of
condenser discharges. B, battery; R, rheochord ; c, rider of rheo-
chord ; S, switch (Pohl's reverser without cross wires) ; C, conden-
ser ; n, nerve ; m, muscle ; e, non-polarisable electrodes.

connection either with the battery from which it receives its charge or with the
nerve through which it can discharge. By knowing the capacity of the con-
denser and the electromotive force by which it is charged, we can estimate the
energy of the charge sent through the nerve.

E (energy in ergs) - = 5 F V-
(F ^ capacity in microfarads ; V = electromotive force in volts).

' For explanation of condenser see Appendix.

- An erg is the amount of work produced or energy expended by the action
of one dyne through one centimetre.

A dyne is the force which will give to a mass of one gram an acceleration of
one centimetre per second per second.

176 PHYSIOLOGY

In this way it has been found that the energy of a minimal effective stimulus
for frog's nerve is about j~^^ of an erg.

From what we have previously said about the relation of the rate of change
of current to its excitatory effect, it is evident that the amount of energy neces-
sary to excite the nerve will vary with the rate at which the condenser is allowed
to discharge through the nerve. This rate can be modified by altering the resist-
ance in the discharging circuit or by altering the electromotive force of the
charge ; and this method has been adopted by Waller in determining the so
called ' characteristic ' of nerve, viz. the rate of change at which excitation is
obtained with a minimal expenditure of energy.

NERVE-FIBBES (CONDUCTING TISSUES) 177

Section 4

THE CONDITIONS AFFECTING THE ACTIVITY
OF NEEVE

The hifiuence of Fatigue

In the description of the phenomena of muscular fatigue
given in the last chapter it was assumed that the muscle
was being excited directly. The same phenomena are how-
ever observed when the muscle is excited through its nerve,
though in this case fatigue comes on much more quickly. If,
after the muscle has been excited in this way until exhausted,
it be excited directly, it will respond with a contraction
nearly as high as at the beginning of the experiment. We
see therefore that the nervous structures are more susceptible
to the influences causing fatigue than the muscle itself, and
it can be shown that the weak point in the nerve-muscle
preparation is not the nerve, but the end-plates. In fact it
is not possible to demonstrate any phenomena of fatigue in
the nerve-trunk. This fact can be shown in mammals by
poisoning the animal with curare, and then stimulating a
motor nerve continuously while the animal is kept alive by
means of artificial respiration. As the effect of the curare on
the end-plates begins to wear off in consequence of its excre-
tion, the muscles supplied by the stimulated nerve enter into
tetanus.

The same fact may be shown on the excised nerve-muscle
preparation of the frog. The gastrocnemii of the two sides
with the sciatic nerves are dissected out, and an exciting circuit
is so arranged that the interrupted secondary currents pass
through the upper ends of both nerves in series. At the same
time a constant cell is connected with two non-polarisable
electrodes {np, np) placed on the nerve of B, so that a current
runs in the nerve in an ascending direction. The effect of
passing a constant current through a nerve is to block the
passage of impulses through the part traversed by the current.
When the constant polarising current is made, the muscle B
may give a single twitch, and then remains quiescent. The
exciting current is then sent through both nerves by the

12

178

PHYSIOLOGY

electrodes e, and e,. The muscle A enters into tetanus, which
gradually subsides owing to ' fatigue.' When A no longer
responds to the stimulation, the constant current through the
nerve of B is broken. B at once enters into tetanus, which
lasts as long as the contraction did in the case of A, and
gradually subsides as fatigue comes on. Since both nerves
have been excited throughout, it is evident that the fatigue
does not affect the nerve-trunk. We have already seen that
a muscle will respond well to direct stimulation when stimula-
tion of its nerve is without effect, and must therefore conclude

Fig. 84.

A B

Arrangement of experiment for demonstrating the absence of fatigue
in medullated nerve-fibres, ec, exciting circuit ; cp, polarising
circuit.

that the first seat of fatigue is the junction of nerve and
muscle, i.e. the end-plates.

In the normal intact animal, the break in the neuro-
muscular chain which is the expression of fatigue occurs still
higher up, i.e. in the central nervous system, and is probably
due to some reflex mhibition of the central motor apparatus
from the muscle itself. Thus after complete fatigue has been
produced in a muscle so far as regards voluntary efforts, direct
stimulation of the muscle itself or its nerve will produce
a contraction as great as would have been the case at the
beginning of the experiment.

NERVE-FIBRES (CONDUCTING TISSUES) 179

The E^ffect of Injury —The Bitter-VaUi Lato

The irritability of the nerve of a muscle-nerve preparation
is not equal in all parts of its course, but is greater at the
upper end, probably in consequence of the proximity of the
cross-section.

Some time after a motor nerve is divided, the increased
irritability at the upper end gives way to a decreased irrita-
bility, and this decrease goes on till the nerve is no longer
excitable. The diminution in excitability gradually extends

Fio. 85.

Tracing of muscle contractions to show effect of cooling a nerve on ity
excitability. The lower line indicates the changes in temperature of
the excited part of the nerve. The muscle responded only when the
nerve was cooled, the stimulus becoming ineffectual when the nerve
was warmed (Gotch).

down the nerve-fibre, so that the part of the nerve nearest
the muscle remains excitable the longest. This progressive
change in the irritability of a nerve after section is spoken of
as the Eitter-Valli law. It is soon followed by definite histo-
logical changes in the nerve, which we shall describe later on
(see Chap. XIV.).

The Influence of Temperature

The excitability of a nerve is, within certain limits, in-
creased by cooling the nerve, and diminished by raising its
temperature (Fig. 85). ^ Thus, if a frog be cooled to 2° or 3° C.

' This is true for all stimuli except induction-shocks and extremely short
galvanic currents (less than 0-005 sec), with which the irritability of nerve is
increased by warming and diminished by cooling. The same appears to be
true for ventricular cardiac muscle, but in the case of voluntary muscle the
excitability for all forms of stimuli is increased by cooling. (Gotch.)

180 PHYSIOLOGY

for a day, it will be found that simple section of its sciatic
nerve may suffice to send the gastrocnemius into continued
contraction, and under these circumstances * closing tetanus '
may be obtained with the greatest ease. The opposite effects
of cooling on the conductivity and excitability of nerves show
that these properties are possibly independent, and are not
affected by the same conditions.

The Inflitence of Drugs

The most important drugs with an influence on nerve-
fibres are those belonging to the class of anaesthetics. Of
these we may mention carbon dioxide, ether, chloroform, and
alcohol.

The action of any of these substances on the excitability and conductivity
of a nerve may be studied by means of the simple apparatus represented in
Fig. 80. The nerve of a nerve-muscle preparation is passed through a glass tube

Fig. 86.

which is made air-tight by plugs of normal saline clay surrounding the nerve
at the two ends of the tube. By means of two lateral tubulures a current of
CO2, or air charged with vapour of ether or other narcotic, can be passed through
the tube. The nerve is armed with two pairs of electrodes which are stimu-
lated alternately, the pair within the tube serving to test the action of the drug
on the excitotiZi^y, while the pair outside the tube shows the presence or absence
of any effect on the conducting iMwer of the nerve below it.

Of the gases and vapours mentioned above, CO., and
ether both diminish and finally abolish the excitability and
conductivity of the nerve-fibres. The conductivity however
persists after all trace of excitability has disappeared, before
in its turn being also abolished, On removing the gas or

NERVE-FIBRES (CONDUCTING TISSUES) 181

vapour by blowing air over the nerve, the conductivity and
excitability gradually return in the reverse order to their
disappearance (Fig. 87).

Alcohol is said to increase the excitability or leave it
unaffected, while diminishing the conductivity of the nerve.

Fig. 87.

Tracing to show the effect of ether on excitability and conductivity of
nerve. Nerve excited by single induction-shocks alternately within
and above ether chamber. The vertical lines indicate contractions
of the muscle (gastrocnemius). The lower line indicates the periods
during which the nerve was exposed to the action of ether, a, dis-
appearance of excitability; b, reappearance of excitability; c, dis-
appearance of conductivity ; v, reappearance of conductivity. (From
a tracing kindly lent by Prof. Gotch.)

Chloroform rapidly abolishes both excitability and con-
ductivity. It is a much more severe poison than the drugs
just mentioned, so that in many cases its effects are per-
manent, and no, or only a very partial, recovery of the nerve
is obtained on removal of the chloroform vapour from the
apparatus.

182

PHYSIOT,OGY

Section 5
POLAEISATION PHENOMENA IN NEEVE

Electrotonic current.— In describing the effects of the
passage of a constant current through a nerve, we only
mentioned alterations of irritability. There are however
various other phenomena which are more purely physical in
their nature.

If a constant current be passed through a nerve-fibre
through the electrodes (x) and (y) — (x) being the anode and
(y) the kathode — and the extrapolar portions of the nerve

Fio. S8.

^ -SV-^

Gi G2

Diagram showing electrotonic currents. P, polarising circuit;
G' G'-, galvanometers.

(ab, cd) be connected with galvanometers, it is found that the
needles of both are deflected, and the direction of the deflection
shows the existence of a current in the extrapolar portions of
the nerve (a) to (b), and from (c) to (d).

The galvanometers will indicate, before the passage of the polarising current,
the ordinary demarcation current of the nerve resulting from the cross-section
at the upper end. This current flows, in the outer circuit, from equator to cut
end, and therefore in the nerve-fibre from (a) to (b), and from (d) to (c). The
effect of closing the polarising current will be to increase the current of rest
between (a) and (b), and to diminish that between (c) and (d).

We thus see that the passage of a current through a part
of a nerve gives rise to a current flowing through a consider-
able portion of the nerve-fibre on each side of the polarising

NERVE-FIBRES (CONDUCTING TISSUES) 183

current and in the same direction. This current is called
the electrotonic current. It must not be confounded with
the current of action, which originates at one of the poles,
only at make or break of the current, and is transmitted
thence in the form of a wave with a measurable velocity
of about 30 metres per second. The electrotonic current
is developed instantaneously, and lasts the whole time that
the current is flowing through the nerve. Its production
is dependent on the occurrence of polarisation between the
sheathing and conducting part of the nerve-fibre and may be
exactly reproduced on a model consisting of a core of zinc or
platinum wire in a casing of cotton soaked with ordinary salt
solution. Although thus physical in origin, its production is
dependent on the vitality of the nerve, and so is not to be
confounded with the simple spread of current.

Glass tube

containing 0-6% Na Cl.

Pt.wire

Apparatus for iruitating the polarisation phenomena in medullated
nerve (' Kcrnlciter ' model).

The polarisation phenomena resulting from the passage of
a constant current through a medullated nerve can be studied
on a model made up of a glass tube filled with normal salt
solution, containing a platinum or zinc wire stretched through
it (Fig. 89). On leading a current through a and b, and
connecting c and d with a galvanometer, a current will be
observed in the extrapolar portion of the model in the same
direction as in the intrapolar. That this spread of current is
due to polarisation is shown by the fact that, if the model
be made of zinc wire immersed in saturated zinc sulphate
solution, where no polarisation can occur, the spread of
current to the extrapolar area is also wanting. If we ex-
mine the phenomena taking place at the anode, we see that a
current passes here through an electrolyte to the conducting
core. Every passage of a current through an electrolyte
must be accompanied by dissociation, the current being carried

184 PHYSIOLOGY

by the ions. We get therefore a movement of negative ions
up into the electrode, and a deposition of electro-positive
ions on the core (Fig. 90, a). In the same way at the kathode
there will be a deposit of electro-negative ions on the core
(Fig. 90, d), so we may say that the core is positively
polarised at the anode and negatively polarised at the kathode.

Vm. 90.

♦ -+ - * - + + . + + -

c b a d e f

Diagram to show polarisation at the surface between conducting
core and electrolyte sheath in a ' Kcrnleiter.'

This polarisation, while opposing the primary current, will
set up currents in the surrounding electrolytic sheath, as
shown by the arrows in Fig. 91, the current passing from
a to 6 and from 6 to c in the electrolyte, returning towards a in
the core. Hence if we lead off from the sheath in the neigh-
bourhood of the anode from a and c, a current will pass in the
galvanometer from a to c, that is, along the core in the same

Fig. 91.

y^KX

d e (

Diagram to show polarisation currents in a ^Kcrnleiter,' or in a
medullated nerve.

direction as the intrapolar current. The same factors will
cause an extrapolar current in the kathodic area, the katelec-
trotonic current.

It is evident that this polarisation will not disappear at
once on breaking the polarising current. The nerve or nerve-
model will still be positively polarised at the anode and
negatively polarised at the kathode. On connecting therefore

NERVE-FIBRES (CONDUCTlNa TISSUES) 185

these two points with the galvanometer, we shall get a current
in the opposite direction to the previous polarising current,
viz. from anode to kathode (Fig. 92). This is the so-called
negative polarisation of nerve. Similarly in the extrapolar
regions of the nerve, we shall have currents in the same
direction as the previous polarising current, as shown by
the arrows. So far then the nerve behaves exactly like the

/ \

Fig. 92,
Polarising

\V^ ^ // Neqative polarisation.
Diagram to show direction of the negative polarisation current.

mechanical model. If however we pass a very strong current
through a nerve, and then quickly switch the nerve on to
a galvanometer, we find a momentary current through the
galvanometer in the same direction as the previous polarising
current. This is known as positive polarisation of nerve.
It is absolutely dependent on the living condition of the
nerve, and is in fact an excitatory phenomenon due to the
strong excitation which occurs at break of the current at the

Fig. 93.
/^I rx Polarising

a/ ' -^ V

I "Mini -I

'-/Ty-'^^ Positive polarisation

Diagram to show direction of the positive polarisation current,
due to a break excitation at the anode.

anode. Thus in the diagram (Fig. 93) a strong current is
passing through the nerve from a to k. When this current
is broken, excitation occurs, as we have already learnt, at the
anode, and this excitatory state may, if the previous currents
were strong, last two or three seconds. An excited tissue is
however always negative towards adjacent unexcited tissue,
and therefore if we connect a to k, there must be a current
outside the nerve from k to a, and in the nerve from a to k,

im PHYSIOLOGY

viz. in the same direction as the polarising current. We see
therefore that negative polarisation is due to polarisation
occurring between an electrolytic sheath and a conducting
core, whereas positive polarisation is hardly a polarisation
effect at all but is a current of action.

Paradoxical contraction. —If the sciatic nerve of a frog
be dissected out, and one of the two branches into which it

Diagram of arrangement for showing paradoxical contraction.

divides be cut, and the central end of this branch stimulated,
the muscles supplied by the other half of the nerve contract
to each stimulus. Ligature or crushing of the nerve (x)
between the points stimulated and the point which joins the
main trunk puts a stop to this effect, showing that it is not
due to a mere spread of current. The fibres passing down
(n) are in fact stimulated by the electrotonic current developed
in (x) during the passage of the exciting current.

NERVE-FIBRES (CONDUCTING TISSUES) 187

Section 6
THE NATUKE OF THE NEEVOUS IMPULSE

It has been a subject of much debate what the exact
nature of the nervous impulse really is, and how it is trans-
mitted down the nerve. We have no other evidence of the
passage of an impulse down a nerve than the current of action
accompanying the impulse, and the result of the arrival of
the impulse at the terminal organ, whether it be contraction
of muscle, secretion of gland, or production of sensation in
the central nervous apparatus. Since all these effects may be
produced by electrical stimulation of the end-organs them-
selves, it has been thought that the wave of ' negativity ' is
the nervous impulse ; that is to say, that the current pro-
duced in any given section of the nerve-fibre, when it is
stimulated and so becomes negative, excites the adjacent
segments or molecules, causing them to become negative, and
thus setting up another current of action, which in its turn
excites the molecules next in order ; and that in this way
the excitatory process travels the whole length of the nerve.
A natural corollary of this view would be that the normal
excitation of nerve-fibre in the brain or at the periphery
is also brought about by electrical means. There are how-
ever considerable difficulties in the way of accepting this
hypothesis. Although we can to a great extent imitate the
results of the natural excitation of nerve-fibres by artificial
electrical stimulation, yet the phenomena in the two cases do
not run exactly parallel, and many differences are found to
exist between the two forms of stimulation.

One of the most striking examples of this difference is
the varying nature of the muscular contraction as produced by
electrical stimulation or by natural (voluntary) stimulation.
In dealing with the physiology of muscle, we saw reason to
conclude that the natural contraction of muscle is a con-
tinuous one, although our only certain way of producing an
approximate resemblance of such a contraction was by the
use of discontinuous electrical stimulation.

188 PHYSIOLOGY

An attempt has been I'ecently made by Boruttau to explain the nerve-
process, not as a wave of electrical change affecting the substance of the
axis-cylinder itself, but as a propagated katelectrotonic current. This
observer found that by working with a 'platinum core model' {' Kernleiter')
(Fig. 89) of considerable length, the katelectrotonic current was developed
at one end of the model some appreciable time after a current had been sent in
at the other end, thus resembling a current of action.

It is however impossible to explain all the electrical phenomena of nerve
as due simply to polarisation. We might go so far as to assume that the
excitatory effect at the kathode is due to negative polarisation, and that ex-
citation at break, i.e. at the anode, is caused by the sudden coming into
existence of a negative polarisation current ; but then it would be impossible
to understand how the excitation, so produced at the anode, should give
rise to a current so much exceeding the current which produced it, that
it would appear in our external circuit as a current of positive polarisation.
We must in fact conclude that the axis-cylinder of the nerve is endowed
with an energy of its own, which is let loose, so to speak, under the influence
of chemical or electrical changes, just as the energy of a contracting muscle
is set free by the exertion of an infinitesimal force applied as a stimulus.
The nerve does not simply transmit the energy which is imparted to it, like
a telegraph wire, but itself furnishes the energy of the descending nerve-
process.

Against this view might be urged the absence of phenomena of fatigue in
nerve, as showing that nervous activity is not accompanied by any expenditure
of energy or using up of material. But it must be remembered that this
absence of fatigue holds good only for meduUated nerve-fibres and is not
found in non-medullated nerves, and even in meduUated nerves the persistence
of irritability is dependent on the continual supply of a certain small amount
of oxygen. It may therefore possibly be explained by a continual process of
restitution taking place at the expense of the sheath. Fatigue is absent, not
because nothing is used up, but because the assimilative changes exactly
balance and make good the dissimilation involved in the propagation of a
nervous impulse.

X89

CHAPTER VI
THE VASCULAR MECHANISM

Section 1

THE MECHANICAL PRINCIPLES OF THE
CIRCULATION

Structure and Properties of the Blood-vessels

We have now to study more fully the manner in which
the continuous circulation of the hlood through the body is
carried on.

It will be remembered that the vascular system consists
of a closed system of tubes divided into two circuits, known
respectively as the greater or systemic circulation, and the
lesser or pulmonary circulation, both connected with a cen-
tral pumping organ, the heart, in the thorax. By means of
the pumping action of the heart a continuous stream of blood
is kept up from the right side, through the lungs, back to
the left side of the heart, whence the blood is sent by the
contraction of the left ventricle through all the rest of the
body, and is returned by means of the superior and inferior
venae cavse to the right side of the heart, so completing the
double circuit. The blood-vessels vary considerably in struc-
ture according to their situation in the circuit. The vessels
which carry the blood from the heart to the tissues, the
arteries, are thick-walled, and contain an abundance of
muscular and elastic elements in their walls. The typical
medium-sized artery is described as consisting of three coats
(Fig. 95) : an intima lined by a continuous layer of flattened
endothelial cells, which rest on a well-marked lamina of
yellow elastic tissue ; a media composed of unstriated mus-
cular fibres arranged longitudinally and circularly ; and an
external coat or adventitia of fibrous tissue, with a number

190 - PHYSIOLOGY

of longitudinal elastic Hbres. Near the heart, in the great
vessels such as the aorta and its larger branches, there is a
preponderance of elastic tissue as compared with the muscular ;
and we find in the media alternate layers of muscle-fibres
and fenestrated elastic membranes. In the smallest arteries,
on the other hand, the arterioles, the elastic element entirely
disappears, so that the wall consists of muscle-fibres, chiefly
circular, lined by the endothelium. It is evident that in
these latter vessels a contraction of their walls may result in
an entire obliteration of their lumen. Judging simply from
the structure of these vessels, one might guess that the chief
function of the large arteries is to serve as elastic conduits,
whereas that of the arterioles is to regulate the amount of
blood flowing through them, and therefore the vascular supply

Fig. 95.

Transverse section of part of the wall of the posterior tibial artery
( X 75). a, endothelial and subendothelial layers of intima ;
6, lamina of elastic tissue ; c, media consisting of muscle-fibi'es ;
d, adventitia. (Schiifer.)

to the tissues beyond. As the arteries branch there is a
gradual enlargement of the total cross-section of the system
of tubes, although the individual tubes become progressively
smaller.

Although the muscle-fibres in the coats of the aorta and large arteries cannot
by their contraction alter appreciably the flow of blood through these tubes,
they have nevertheless an important function. Like all other kinds of un-
striated muscle, they are extremely susceptible to changes of tension. Any
sudden increase in the pressure within the arteries will therefore excite these
fibres to contract, so that the muscular tissue is able to support and reinforce
the inert elastic tissue of the arterial wall in withstanding any sudden strain
caused by a great rise of arterial pressure. The muscle-fibres in the arteries
have in fact the same protecting function on the connective tissue elements that
is exercised (but by a more complex mechanism) by the skeletal muscles which
send their tendons across a joint. In the latter case, as we shall see later, any
sudden stretching of the tendon excites the corresponding muscle to contract,
so taking the strain of the joint movement off the ligamentous structures which
surround it.

THE VASCULAR MECHANISM

191

In the tissues themselves the blood flows through a close
network of canals — the capillaries. In these all the elements
of the vascular wall have disappeared, except the endo-
thelium, so that the blood may come in closest possible con-
nection with the tissues, without actual extravasation into
the tissue-spaces. Owing to the great number of these
capillaries, the vascular bed undergoes a sudden enormous
enlargement as we proceed from arterioles to capillaries.

The blood is collected from the capillaries into small
venous radicles, which unite to form larger and larger veins.

Capacity iu c.c.

Fig. 96.

\, /- — I 1 1 1 1 .

-74—1 n ^-^^''

120 130 140 ISO 160

Curves of distensibility of an artery (thick line) and of a vein (thin
line). The figures at the left side of the diagram represent the
capacity of a section of the vessel when distended under a certain
pressure, expressed by the figures on the base line in mm. Hg.
(Constructed from figures given by Koy.)

Although in the vein we can distinguish by dissection the
same three coats as in the typical artery, the thickness of
the wall of the vein is very much less in proportion to its
lumen than is the case with the arteries. There is moreover
a diminution of the muscular and elastic, and a relative
increase of the fibrous tissue-elements of the wall. A
vein therefore collapses altogether, unless distended by some
internal pressure.

This histological difference between veins and arteries
is of considerable importance for the understanding of the
distribution of pressures in the vascular system, since the

192 PHYSIOLOGY

distensibility and reaction to pressure of these vessels are
conditioned by their structure. In Fig. 96 is represented the
extensibility, i.e. the increase in capacity of an artery and
a vein under gradually increasing internal pressure. It will
be seen that an artery which has a certain capacity at zero
pressure, gradually distends with increasing pressure. The
increase in capacity is however small at first, and becomes
most rapid between 90 and 110 mm. Hg. After this
point every increment of pressure brings about a gradually
diminishing increment of capacity. Thus a change of in-
ternal pressure causes the greatest change in capacity when
the pressure in the artery corresponds, as we shall see, to
the average arterial pressure in the normal animal.

In the vein, on the other hand, the capacity, which is
nothing at zero pressure, becomes considerable on raising the
pressure to 1 mm. Hg. A further rise of pressure to 10 mm.
Hg. causes a considerable increase in volume, but from this
point the increments of volume with rising pressure rapidly
diminish. Whereas therefore the artery is most distensible
at about 100 mm. Hg., the vein has its limits of optimum
distensibility between 0 and 10 mm. Hg.

The Blood-pressure

If an artery in the living animal be cut across, blood
spurts from it to a considerable height, escaping in jerks
corresponding to every heart-beat. This fact, which shows
the existence of a certain amount of pressure on the blood in
the artery, may be illustrated in another way. If a vertical
glass tube be connected with the central cut end of the carotid
artery, the blood will rise in it to a height of three feet (in
the rabbit), or still higher in the case of the dog, and remain
about this height, rising a little with every heart-beat, and
falling again between the heart-beats.

We thus see that the blood in the artery is under a con-
stant pressure, which varies to a slight extent with the heart-
beats, rising with and sinking between the beats, but never
approaching the line of no pressure.

This blood-pressure may be more conveniently measured and its variations
studied by means of an instrument called a manometer. If we simply
measure the pressure by inserting a vevtical tube into the cut central end of aa

THE VASCULAR MECHANISM

193

artery, the animal is injured by the loss of the blood which is necessary to fill
the tube, and the experiment is soon stopped by the clotting of the blood in
the tube.

There are many different forms of manometer. The best for investigating
changes in the mean arterial blood-pressure is Ludwig's mercurial manometer.
This instrument consists essentially of a U-tube with two vertical limbs about
eighteen inches long. This is half filled with clean mercury. On the surface
of the mercury in one limb is a float, from which a stiff fine rod (of steel or
glass) rises, bearing on its upper end a writing point. This point is adjusted
so as to record its movements by scratching a white line on the smoked paper
of a kymograph. (A kymograph is merely an arrangement of revolving

Fig. 97.

Arrangement of apparatus for taking blood-pressure tracing, a,
artery (carotid) ; c, cannula ; d, three-way cock ; m, mercurial
manometer ; b, drum covered with smoked paper.

cylinders, moved by clockwork or other means, arranged to carry a roll of
smoked paper.) Instead of using the smoked paper, a pen may be fitted to the
end of the vertical rod, and its excursions recorded in ink on a moving band of
white paper.

The other limb of the manometer is connected by a flexible rigid tube (such
as lead) with a small tube or cminula, which is tied into the central end of the
artery. While the cannula is being tied, a clip is placed on the artery at (a),
so as to prevent the blood escaping. At (d) there is a three-way cock. This is
first turned so as to put the tube (x) into connection with the tube to the
cannula, and the whole is then filled with a half-saturated solution of sodium
sulphate, or a 25 per cent, solution of magnesium sulphate. The cock is then
turned and the tube leading to the manometer filled in the same way

Both tubes being full, the solution is injected forcibly into (x), so as to
raise the column of mercury about 150 mm. The cock is then turned so

u

194 PHYSIOLOGY

that the manometer is put into connection with the artery. The clip is then
talien oE tlie artery. Tlie column of mercury drops to about 120 mm. (if the
carotid of the dog is the artery used), and stops at about that level, rising and
falling slightly with every heart-beat. The object of using sodium sulphate or
magnesium sulphate solution is to delay clotting in the cannula.

On investigating in a similar manner the condition of the
veins, we find quite a different state of things. If a vein be
ligatured in any part of its course, it swells up on the distal
side and shrinks on the side towards the heart. If it be cut
across, the bleeding that occurs takes place nearly entirely
from the distal end. The haemorrhage moreover is of a
different character from that which occurs when an artery is

Fig. 98,

Blood-pressure tracing taken with mercurial manometer (from
carotid of rabbit). A, abscissa or line of no pressure.

divided. The blood, instead of spui'ting out to a distance,
wells up and is not increased or in any way affected by the
heart-beat. If we connect a manometer with a vein, we find
that the pressure amounts to a few mm. of mercury. Thus
we see that the blood, which in the arteries is under high
pressure and has an intermittent flow, by the time it has
reached the veins is at a low pressure, and the flow has lost
its intermittent character.

What is the cause of this change in the character of the
flow? The blood in passing from arteries to veins has to
traverse the arterioles and capillaries and in so doing meets
with considerable resistance owing to the friction between the
blood and the vessel-walls. Every time an artery divides,
although each separate branch is smaller than the original
branch from which it springs, the united sectional area of the

THE VASCULAK MECHANISM 195

two branches is greater, so that the sectional area of the
capillaries exceeds by many hundred times that of the aorta.
If this increase in the sectional area took place without
division, its effect would be to lower resistance to the flow of
blood. But if we consider for a moment the condition of the
circulation of the capillaries, we see that the friction-lowering
efBfect of increased area is much more than compensated for
by the increased surface and therefore increased friction.
Many of the capillaries are no wider than a single blood-
corpuscle. The resistance of such a capillary system would
be very large even to a stream of water, much more so then
to a fluid which is somewhat viscid, and has suspended in it
a number of solid particles.

Another factor however is involved in this question of
resistance. The friction between the blood and the walls of
the vessels depends not only on the extent of surface-con-
tact, but also on the velocity of the blood. Owing to the
great increase in area on passing from arterioles to capillaries,
there is a sudden slowing-down of the blood-stream. The
arterioles may be compared to small inlets into a wide lake.
On this account it seems that the main resistance to the
passage of blood through the tissues is situated, not in the
capillaries but in the arterioles, and may be varied within
very wide limits by alterations in the calibre of these vessels.

The main factors in converting the intermittent flow of
the arteries into a constant flow through capillaries and veins
and in maintaining a mean blood-pressure in the arteries
are —

1. The contraction of the heart.

2. The peripheral resistance.

3. The elastic reaction of the arterial walls.

Since this is a purely mechanical question, it will be more
easily understood by a simple illustration. The heart may
be regarded as a pump, forcing a certain amount of blood
(about 3 oz.) into the circulation at each stroke. If a pump
be connected with a rigid tube, every time that a certain
amount is forced into the beginning of the tube, an exactly
equal quantity will be forced out at the other end at the
same time. Increasing the peripheral resistance by partial
closure of the end of the tube will not afiect the intermittent
character of the flow, but will merely serve to diminish the

196 PHYSIOLOGY

quantity thrown in, as well as the quantity which escapes at
the other end of the tube, supposing that the work done by
the pump is equal in both cases. If, instead of a rigid tube,
we employ an elastic tube, and the end be left open so that
no resistance is offered to the outflow of the fluid, the effect
will be the same as when we used the rigid tube ; the outflow
will correspond exactly to the inflow, and will be just as inter-
mittent. But now, if the end of the elastic tube be partially
clamped, so as to increase the resistance to the outflow, there
will be a marked difference between this effect and that pro-
duced by the rigid tube. Each stroke of the pump forces
a certain amount of fluid into the tube. Owing to the
peripheral resistance, this cannot all escape at once, and so part
of the force of the pump is spent in distending the walls of the
tube, and part of the fluid that was forced in remains in the
tube. The distended elastic tube however tends to empty
itself, and forces out the fluid which over-distends it before
the next stroke of the pump occurs. So now the outflow may
be divided into two parts, — one part which is forced out by
the immediate effect of the stroke of the pump, and another
part which is forced out by the elastic reaction of the tube
between the strokes. If the strokes be rapidly repeated
before the tube has time to thoroughly empty itself, it will
get more and more distended. Greater distension means
stronger elastic reaction, and therefore stronger outflow of
fluid between the beats. This distension goes on increasing
till the fluid forced out between the strokes by the elastic re-
action of the wall of the tube is exactly equal to that entering
at each stroke, and the outflow thus becomes continuous.

The same thing occurs in the living body. A man's
heart at each beat or contraction forces about three ounces
of blood into the already distended aorta. The first eftect of
this is to distend the aorta still further. The elastic reaction
of the walls drives on another portion of blood, which distends
the next segment of the arterial wall, and so the wave of
distension is transmitted with gradually decreasing force
along the arteries. This wave of distension is what we feel
on the radial artery, or any exposed artery, as the pulse.
After each heart-beat the arteries tend to return to their
original size, and drive the blood on through the arterioles
(the peripheral resistance) into the capillaries and so into the

THE VASCULAE MECHANISM

197

veins. By the time the blood has reached the veins, all
trace of the heart-beat has disappeared, and the pressure has
fallen to a few mm. of mercury.

The accompanying diagram represents roughly the dis-
tribution of pressure along the vascular system. The blood-
pressure falls only slowly in the great arteries, as is shown by
the line bp in the first part of section a. Towards the end of
this section there is a sudden and extensive fall of pressure
caused by the increase of resistance in the arterioles. In the
capillaries (c) and in the veins (v) the blood -pressure once
more falls gradually until, in the big veins near the heart, it
may be negative.

Fig. 99.

Scheme of blood-pressure in — a, the arteries ; c, capillaries ; and
V, veins, oo. Line of no pressure, lv. Left ventricle, ra.
Eight auricle, bp. Height of blood-pressure.

The following table may serve to give some idea of the
probable average height of the blood-pressure at different
parts of the vascular system in man. It must be remembered
however that these pressures are all subject to considerable
variations according to the physiological condition of the
various parts and organs of the body.

Large arteries {e.g. carotid)

Medium arteries {e.g. radial)

Capillaries

Small veins of arm .

Portal vein

Inferior vena cava .

Large veins of neck

+ 140 mm. mercury.
+ 110 mm. „

about -r 15 to -f 20 mm. mercury.

+ 9 mm. „

+ 10 mm. „

-1- 3 mm. „

from 0 to - 8 mm. „

These main facts of the circulation can be well illustrated
on a model made of indiarubber tubing, such as the artificial
schema represented in Fig. 100. (b) is a basin of water, (e)
an enema syringe, which can be used to force on water, and
represents the heart. This is connected by an indiarubber

198

PHYSIOLOGY

tube (a) with a tube (c-) ^vhich is packed with sponges to
represent the peripheral resistance in the capillaries. From
the distal end of (c-) a tube (v) serves to conduct the lluid

Fig. 100.

Diagram of artificial circulation schema.

back to the basin. To side branches of (a) and (v) two
mercurial manometers (m' and m-) are connected, and these
are arranged to write one below the other on the smoked
surface of a kymograph. Another route for the fluid from
(a) to (v) is aflbrded by the tube (c'), which may be clamped

Fig. 101.

Tracing taken from artificial schema with slight peripheral
resistance (Foster), a, arterial ; v, venous manometer.

at will. Tracings are first taken of the pressures on the
arterial and venous sides with the tube (c') open, while the
fluid is forced through the system by rhythmical compression

THE A'ASCULAR MECHANISM

3 99

of the bulb of the enema. The tiuid in passmg from (a) to (v)
has now practically no resistance to overcome, and accordingly
we find the pressm-e-tracings of the two manometers (Fig. 101)
are almost identical, the fluid escaping from the end of (v) at
each stroke of the pump.

c' is now clamped so that all the fluid must pass through
the tube (c'-) with a high resistance. Tracings are again
taken (Fig. 102), and they show that the pressure on the
arterial side at first rises with every beat till it has attained a

Fig. 102.

Tracing from artificial schema with considerable peripheral
resistance, a, arterial ; v, venous manometer.

certain height, where it remains stationary, merely oscillating
with every stroke of the pump. The venous manometer, on
the other hand, shows scarcely any rise of pressure, and its
oscillations become less and less till they disappear, and the
flow becomes continuous.

There is one feature in the circulation which is not represented in the
above schema. In the latter the system of tubes is open at both ends, and
the amount of fluid supplied to the contracting heart-model is constant. In
this model therefore, so long as the resistance in the circuit is constant, the
pressure in all parts of the circuit will vary directly with the force of the
heart-beat, and a rise of arterial pressure will be attended with a smaller rise
of venous pressure, as shown in Fig. 102. In the body however the blood-
vessels form a closed circuit, containing a certain invariable quantity of fluid.
We may imitate this condition in the schema by connecting the venous end of
the tube with the supply-tube of the enema syi'inge, having previously over-

200 PHYSIOLOGY

filled the system to a slight extent. Under these circumstances, so long as
the heart is not beating, the pressure in all parts of the system will be the
same, and this pressure, which may be called the mean general blood-pressure,
amounts in a large dog to about 10 mm. Hg. It will be seen at once that the
pump or heart cannot alter this mean general pressure, but can only give
rise to an unequal distribution of the pressure. Thus it may diminish the
pressure in the veins and increase the pressure in the arteries by pumping
the fluid from the veins into the arteries. We may take Fig. 103 to repre-
sent the vascular system, which has a definite capacity and contains a
definite quantity of blood. If the heart (ii) is not acting, and the fluid is
motionless, the pressures at all parts of the system will be the same (10 mm.
Hg.). If now the heart begins to act, it pumps blood from the veins into the
arteries, so that the latter become distended at the expense of the former, and

the arterial pressure rises above, and the venous pressure sinks below, the
mean pressure of the system. It must be remembered that in the body the
tubes forming the veins are much more distensible at low pressures than are
the tubes on the arterial side. Hence, when the heart begins to beat, we get
a large rise of pressure on the arterial side (from 10 mm. to 120 mm.) and
only a small fall of pressure on the venous side (from 10 mm. to 5 mm.,
0 mm., or near the heart about —5 mm.). It is evident that in such a system,
while the resistance remains constant, the venous pressure will vary inversely
with the arterial pressure, and not directly with the latter, as is the case with
an open circuit.

There is one other important fact arising from the closed condition of the
circulatory system. In the body, changes in the peripheral resistance are
effected by contractions of the smaller arteries and of some of the veins. Now
the contractions of these vessels not only increase the peripheral resistance,
but also diminish the total capacity of the system, so that now we have the
same amount of fluid as before enclosed in a smaller cavity. This must mean
an increased elastic distension of the walls of the cavity and a rise of the mean
general pressure, so that a general contraction of the arterioles, the heart-beat
being unchanged, may cause a rise of pressure both on arterial and venous
sides.

It must therefore be remembered that, whenever a rise in arterial pressure
is produced by active contraction of the smaller arteries, it is due to the
coincidence of two factors— (a) increased peripheral resistance, (b) diminished
capacity of vascular system.

THE VASCULAR MECHANISM 201

In the living body there are two aids to the circulation on
the venous side, which are not represented in our schema.

Firstly, nearly all the veins in the body possess valves,
formed by reduplication of their lining membrane. These
valves are so placed that they allow the passage of the blood
only in one direction, viz. towards the heart. Thus any
muscular contraction pressing on the veins can squeeze their
blood only in one direction, and in this manner it assists the
onward flow of blood.

Secondly, as we shall see in treating of respiration, the
movement of the chest-walls at every inspiration causes a
suction of the blood towards the thorax, and it is this aspira-
tion of the thorax which gives rise to the negative pressure
found in the big veins near the heart.

Velocity of the Blood-jioiv in the Vessels

Since the area of the blood-vessels increases progressively
from aorta to capillaries, the rate of flow must decrease in like
proportion. There are several methods by which the rate of
flow in the larger arteries may be measured.

Fig. 104.

't
b
Diagram of Ludwig's ' Stromiihr.^

One of the most important historically is that devised by
Ludwig, in which the ' Stromuhr ' is used. This (Fig. 104)
consists of two oval glass vessels (a) and (b), connected above
by means of a glass tube. The capacity of these vessels is
accurately known. They are fixed at their lower ends in a metal

202 PHYSIOLOGY

disc (c), which is fitted on to another disc. The upper disc can
be turned round on the lower disc. Through the latter run
two tu))es (t) and (f), the upper ends of which are continuous
with the vessels (a) and (b), and the lower ends, which are bent
outwards in a horizontal direction, can be connected with the
central and peripheral ends of a cut artery such as the carotid.
In using this instrument the vessel (a), the connecting tube
as far as the mark (x), and the two tubes (t) and (f) are filled
with defibrinated blood. The vessel (b) is filled up to the
mark (x) with oil. The tube (t) is now fixed into the central
and the other tube (t) into the peripheral end of a cut artery.
As soon as the clips on the artery are released, blood flows
from the artery through (f) into (b), displacing the defibri-
nated blood in (a), which flows into the peripheral end of the
artery. As soon as the inflowing blood has reached the
mark (x), the whole upper part of the instrument is turned sud-
denly round 180°, so that (b) is now in communication with the
tube (t). The blood, which is still flowing steadily into (f),
now rises into (a), driving the oil back into (b), and the blood
in (b) onwards into the peripheral parts of the artery. As soon
as the oil reaches its own level, the instrument is turned round
again into its previous position, and so on. From the number
of times that the ' Stromulir'' has been turned round, we can
reckon the amount of blood that has flowed through in a given
time, and from this number, knowing the calibre of the artery,
it is easy to compute the velocity of the blood in the artery.'

The earliest direct determinations of the velocity of the blood in the larger
vessels were made by Volckmann by means of an instrument called the
licemodromonieter. This consists simply of a U-tube (Fig. 105) of approxi-
mately the same size as the vessel in which the velocity is to be measured.
After being filled with normal salt solution it is connected by its two arms,
a and c, with the proximal and distal ends of the cut vessel. By means of the
taps at a and c, the blood can either flow directly from a to c, or can be
directed so as to flow entirely through the U-tube. In this way the velocity of
the blood is measured by seeing how long it takes for the blood to flow round
the U-tube from a to c.

Both these methods give only the average velocity of the blood in the larger
vessels. In order to determine the rapid changes in velocity which occur
during each pulse, several instruments have been devised.

The liannodromograph of Marey consists of a wide tube with a window at

' If we take v for velocity, vi for volume of blood that has flowed through

in a unit of time, and a for the sectional area of the artery, then v = ~,

a

THE VASCUIiAR MECHANISM

203

one side covered in by a piece of elastic membrane. Through this membrane
passes a writing-point which has an oar-shaped enlargement within the tube.
On placing the tube in the course of a blood-vessel so as to allow blood to flow

Fig. 105.

'<^

Hsemodromometer of Volckmann.

through it, the blood-current causes a deflection of the flattened extremity of
the lever which, communicated to the arm outside the tube, can be recorded
on a blackened surface.

Fig. 106.

Diagram to show principle of construction of Cybulski's photo-
hsematachometer.

A much better instrument for this purpose is the plwtoluTmatachometer of
Cybulski (Fig. 106). If a current of blood be directed along the tube ab

204

PHYSIOLOGY

possessing two vertical side tubes c and d, the pressure at c will be greater
than that at d, since at c the momentum of the moving mass of blood is added
to the lateral pressure of the fluid. A tube of this shape is connected with an
artery, such as the carotid, and the tubes h and h' are attached at the points
c and d. These two tubes are united at their upper extremities. In this case,
so long as the blood flows from a to b, the fluid in h will rise higher than in h',
and the difference in height of the fluid in the two tubes will be proportional
to the velocity of the blood. A graphic record of this difference of pressure is
obtained by allowing a narrow beam of light to throw an image of the menisci
of the two columns of fluid through a slit on to a moving photographic plate.
Such a record is given in Fig. 107. The width of the black space at any point
is proportional to the velocity of the blood at the moment at which this part of
the record was being taken. Of course this instrument has to be calibrated
if we wish to determine the velocity of the blood in absolute measure. In

Fig. 107.

Eecord of blood-velocity in the carotid artery of the rabbit.
(Cybulski.)

Fig. 107 the velocity at the point 1 and 1', corresponding to the cardiac systole,
was 248 mm. per second. At 2 and 2', corresponding to the dicrotic elevation,
the velocity was also 248 mm. At 3 and 3', towards the end of diastole, the
velocity sank to 127 mm.

The rate of flow in the capillaries may be measured by
direct observation of the rate at which a blood-corpuscle moves
along a capillary of the frog's web. It probably varies from
^ to 1 mm. per second. The area of the large veins near the
heart (under normal pressure) is equal to about twice that of
the arteries, and this relationship between veins and arteries
holds good for the entire system. Hence, since the same
amount of blood enters the heart as leaves it at each beat, the
rate of flow in the veins must be about half that in the corre-
sponding arteries.

THE VASCULAR MECHANISM 205

It is also possible to measure the time taken up by the
blood in traversing the whole of the circulation once, the ' total
circulation time.' To this end a solution of sodium ferrocyanide
is injected into the jugular vein on one side, and the time in
seconds is noted that elapses before the salt can be detected in
the samples of blood taken from the jugular vein of the other
side. This time in the horse is thirty-one seconds, and in the
dog seventeen seconds. In man it has been computed to be
about twenty-three seconds.

Many other methods have been devised for the same end. Thus we may
inject a strong solution of a colouring matter such as methylene blue into the
jugular vein, and determine by actual inspection through the wall of the artery
the moment at which the darkly coloured blood arrives at the point under
observation. Or we may use the electrical method ]3roposed by Stewart : a
compensated current is sent through a small section of artery and a galvano-
meter. A little strong salt solution is then injected into the jugular vein on
the opposite side. As soon as the blood containing the stronger salt solution
arrives at the artery, the resistance between the two electrodes is diminished,
the compensation of the current is therefore at once destroyed, and the needle
of the galvanometer is deflected.

It must be noted that the ' total circulation time ' does not represent the
time it would take for the whole mass of blood to pass round the entire circula-
tion once. For in every tube the particles at the centre will move much more
quickly than those in contact with the walls. In the living animal one blood
corpuscle may pass rapidly from the aorta through the widely dilated arterioles
of, e.g., the thyroid gland, while another corpuscle may have to pass slowly
through the constricted vessels of the skin of the foot before returning to the
heart. The circulation time measured by the above methods is merely the
shortest possible time in which a blood corpuscle, taking all the short cuts,
can pass from right ventricle to left ventricle, and from left ventricle back to
right ventricle. The average circulation time, i.e. the time necessary for the
whole mass of the animal's blood to pass once through the heart, is probably
two or three times as great as the times given above.

206

PHYSIOLOGY

Section 2

THE CHANGES OCCUEEING IN THE HEAET AT
EACH CONTEACTION

Anatomical Arrangements of tJie Heart-jmnij)

We have already seen that the heart consists of four
cavities, two auricles and two ventricles, and that each side of
the heart, consisting of one auricle and ventricle, represents a
pump which has for its function the driving of blood through
the pulmonary or the systemic circulation. The muscular
fibres forming the wall of the heart are so arranged that the
contraction of the fibres causes a diminution, and the relaxa-

FiG. lOB.

Muscular fibres from the mammalian heart ( x 425). (Schafer.)

tion an enlargement of the heart-cavities. The contractile
tissue resembles voluntary muscle in presenting a cross and
longitudinal striation, but differs from it in the fact that each
contractile unit is not a fibre but a quadrilateral cell, having
a single nucleus at its centre. These cells are arranged end
to end so as to form fibres and possess no sarcolemma, the
muscle-cells being apparently functionally continuous by
means of fine intercellular protoplasmic bridges. In both its

THE VASCULAR MECHANISM 207

histology and mode of contraction, cardiac muscle takes its
place midway between unstriated and skeletal muscle.

In the mammal the auricles are separated from the
ventricles by a fibrous ring, from which most of the muscle-
fibres of the two cavities take their origin. There is one band
of fibres however, which are continuous across the auriculo-
ventricular junction, taking a course down the intraventricular
septum. It is this bundle which is responsible in the mammal
for the propagation of the contraction from the auricles to
the ventricles. In the ventricles the fibres have for the most
part an oblique course, running from above downwards and
to the left, sinking deeply into the substance of the ventricle
towards its apex, where they make a spiral turn and are con-
tinued up again on the inner surface of the ventricle, ending
in many cases in one of the papillary muscles. Besides these
oblique fibres, there are a number of longitudinal and circular
fibres, of which many are continuous over the two ventricles.

Corresponding with the greater amount of work thrown
on the left ventricle, its wall is about twice as thick as that
of the right ventricle ; and on cutting a section through the
two ventricles in a contracted condition, we see that the thin
wall of the right ventricle lies in the form of a crescent round
the circular left ventricle. The capacity of both ventricles
is approximately equal, amounting in each case to about 140
c.c. (in complete relaxation).

Whereas the ventricles have to pump their contents into
the arteries against a considerable pressure, the sole function
of the auricles is to empty themselves into the relaxed and
flaccid ventricles. We therefore find that the walls of the
auricles are considerably thinner than those of the ventricles.
Their muscle-fibres run both in a circular and a longitudinal
direction, the circular fibres being continued round both
auricles, special rmgs of circular fibres surrounding the
openings of the great veins.

The endocardium which lines the heart-cavities is covered
by a continuous layer of endothelium resting on a little
fibrillated connective tissue and similar to that which lines
the vascular system generally. The auriculo-ventricular
orifices as well as the openings of the aorta and the
pulmonary artery are guarded by valves permitting the
passage of the blood only in one direction. The auriculo-

208

PHYSIOLOGY

ventricular valves are thin flaps of fibrous and elastic tissue
covered on each side with endocardium and projecting down-
wards into the cavities of the ventricles. Their sail-like
margins are connected by thin tendinous cords with nipple-
shaped projections of the muscular walls of the ventricles, the

Fig. 109.

Left auricle and ventricle, with outer side cut away to show chief
points in anatomy of heart (Testut). 1, aorta ; 2, pulmonary
artery ; 3, ant. coronary vessels ; 5, 5', puhiionary veins ; C, left
auricle; 7, auricular appendage; 10, cavity of left ventricle; 11,
12, mitral valves ; 13, 14, papillary muscles ; 16, arrow pointing to
aortic orifice.

so-called papillary muscles. By these attachments the edges
of the valves are kept close together and prevented from ever-
sion under the strong pressure exerted by the contracting
ventricles. These valves are two in number on the left side
of the heart, forming the mitral valves ; while on the right

THE VASCULAR MECHANISM 209

side of the heart, the auriculo -ventricular valves, though other-
wise exactly similar to the mitral valves, are three in number
and are called the tricuspid valves.

From a purely mechanical standpoint, the valves guarding
the arterial orifices are much more perfect than those just
described, which depend for their efficiency on the proper
contraction of the ventricular wall and musculi papillares.
Each orifice is guarded by three valves, which are semilunai
in shape, are attached by their convex borders to the arterial
wall, and present in the middle of their free border a small
fibro-cartilaginous nodule, the corpus Arantii, from which
fine elastic fibres pass to all parts of the valve. The extreme
margin of each valve, the lunula, on each side of the corpus
Arantii, is extremely thin, being formed of little more than
the endocardium. Whenever the pressure in the arteries is
greater than that in the ventricles, these valves are closed,
and the thin margins come in contact with similar portions of
adjacent valves, so preventing the reflux of a single drop of
blood. The borders of the valves under these circumstances
come together in the form of a star composed of three lines at
angles of 120^, the three corpora Arantii being pressed together
at the centre of the star.

No valves are found at the orifices of the great veins into
the auricles, a reflux of blood in this situation during contrac-
tion of the heart being prevented by the contraction of the
muscular rings round the veins, which always precedes the
auricular contraction.

The heart, as well as the roots of the great vessels, lies
almost free in a special serous cavity, the wall of which is
formed by a tough fibrous membrane, the pericardium. This
is attached below to the central tendon of the diaphragm and
above to the arterial trunks. It is lined by a layer of endo-
thelium continuous with a similar layer covering the surface
of the heart. These two surfaces are kept continually moist
by means of lymph, forming the pericardial fluid, so that the
heart can move freely within the pericardium without friction.
One of the chief functions of the pericardium appears to be to
check an excessive dilatation of the heart during conditions
attended by a rise of venous pressure.

14

210 PHYSIOLOGY

The Phenomena of the Normal Beat

If we expose the heart of a mammal, as the rabbit, by
opening the chest, the animal being kept alive by artificial
respiration, it is possible to observe the sequence of events
which happen at each contraction. The first thing to be
noticed is a contraction of the great veins near the heart,
which occurs simultaneously on the two sides. When the
wave of contraction reaches the auricles, these contract
shortly and sharply towards the ventricles, dragging down
with them the auricular appendages, which also take part
in the contraction and become pale and bloodless. This is
followed almost immediately by the contraction of the ven-
tricles, which is more prolonged and forcible. Contraction
of both ventricles occurs synchronously. As we shall show
later, contraction of the ventricles begins at the base and
extends thence to the apex, but the propagation of this con-
traction-wave occurs so rapidly that it is impossible to follow
it with the eye, all parts of the ventricle appearing to con-
tract simultaneously. During contraction, the ventricle
undergoes changes in shape, size, and position, becoming
shorter from above downwards and changing in cross-section
from an elliptical to a circular form, i.e. the heart becomes
more conical. There is at the same time a twisting of
the inferior parts of the ventricle, owing to the oblique course
of the muscular fibres. If the pericardium is opened, this
torsion causes a tilting of the apex forward and to the right
with each contraction. In the normal condition, when the
pericardium is intact, the apex remains almost stationary
during contraction. This is owing to the fact that the peri-
cardium is fixed externally, and the apex could not rise
without causing a vacuum between it and the pericardium.
The shortening of the long axis of the heart is rendered
possible by a change in the position of the auriculo-ven-
tricular groove, which descends with every contraction, the
large arteries elongating at the same time as they are
stretched by the amount of blood thrown into them.

The contraction or systole of the ventricles is followed by
a rapid relaxation, and they remain for some time at rest,
being simply passively filled with the blood flowing in through

THE VASCULAR MECHANISM 211

the great veins and auricles. This period of relaxation and
rest is called the diastole.

The Valvular Mechanisms of the Heart

We may now consider the effect of these cardiac events
on the contained blood. During diastole the blood is flowing
in a steady stream from the inferior and superior vense cavae
into the right auricle and thence into the right ventricle,
the propelling force being supplied by the systemic blood-
pressure and the auxiliary forces already mentioned, i.e.
muscular movement and aspiration of the thorax. As the
great veins contract they simply hurry on their contained
blood into the auricle, which immediately contracts on its
contents, driving them through the open tricuspid valves
into the right ventricle. It must be remembered that there
are no valves at the mouths of the great veins (except in
the great coronary sinus) to prevent reflux of blood into
them during the auricular contraction. They are indeed
unnecessary, the exclusive flow of blood into the ventricles
being determined by the way in which the auricles contract
towards the ventricles, and the low pressure in the ventricles
during diastole. The ventricles during the whole of diastole
have been getting more and more distended by the gradual
inflow of blood. This distension is suddenly increased bj^
the auricular contraction, and then follows almost immediately
the contraction of the ventricles. As the blood is flowing
from auricles to ventricles, reflux currents or eddies must be
formed on the ventricular side of the tricuspid valves,
tending to keep these from being widely opened. Directly
the pressure rises in the ventricles, in consequence of the
contraction of their walls, the valves are forced back till
their edges come in contact and effectually prevent any
reflux of blood into the auricles. The close apposition of
the edges of the valves is further provided for by the
attachment of the chordae tendineae of the papillary muscle to
the adjacent valves. As the ventricle shortens, the papillary
muscles contract, thus preventing the valves from being
forced backwards and rendered incompetent. The eflect of
this contraction of the papillary muscles is that the auriculo-
ventricular valves, which during the diastolic period form

212 PHYSIOLOGY

a truncated cone open towards the ventricle, are dragged still
nearer to the ventricular wall, so that the blood is, as it were,
expressed between two cones (heart-wall and valves). At the
same time the contraction of the circular fibres at the base
of the heart constricts the auriculo-ventricular orifices, so
bringing the valves at their origin close together, and enabling
their inner surfaces as well as their free edges to be apposed
for a considerable extent {v. Fig. 110). The valves being
thus closed, the pressure rises higher and higher in the
ventricle, till it exceeds that in the pulmonary artery.
Directly this is the case, the semilunar valves open and allow
the ventricle to discharge its contents. The flow of blood
from ventricle to artery goes on during the whole systole of

Fia. 110 A. Fig. 110 r.

Diagram to show position of mitral valves in diastole (110 a) and
systole (110 b). A. Auricle. V. Ventricle. Ao. Aorta.

the ventricle ; during this time the semilunar valves are
pressed outwards, but not close to the arterial wall, since they
are probably kept in an intermediate position by the reflux
currents or eddies set up in the blood on their arterial side.
They thus form an orifice, triangular in shape with curved
sides, presenting but little resistance to the onward flow of
blood.

Directly the ventricular contraction ceases and the blood
stops flowing, these reflux currents tend themselves to bring
the valves together. At the same time the pressure in the
right ventricle falls quickly to nothing, and the sudden
difference in the pressures on the two sides of the valves
causes them to shut tightly and sharply, giving rise to a
click which is distinctly audible on listening with one's ear

THE VASCULAR MECHANISM 213

closely applied to the chest-wall, and represents the second
heart-sound. The lunulae of two adjacent valves are closely
pressed together, thus preventing the possibility of the leak-
age of even a single drop of blood back into the ventricle.

While these events are occurring on the right side of the
heart, an exactly similar series is taking place on the left.
During the diastole blood flows from the pulmonary veins
to the left auricle and ventricle. The left auricle then
contracts, and this is followed by the contraction of the
left ventricle. The only difference between right and left
sides consists in the fact that the pressure which has to be
overcome in forcing blood into the aorta is much greater
than that in the pulmonary artery, and so the left ventricle,
having much more work to do, is much thicker, and contracts
more forcibly, than the right. The closure and opening of the
mitral and aortic valves occur in just the same way as the
corresponding events affecting the tricuspid and pulmonary
valves.

The Heart-sounds

If we apply our ear to the front of a person's chest (it is
more convenient to use the stethoscope for the purpose),
we hear two distinct sounds accompanying each beat of the
heart, followed by a pause corresponding to the diastole.
The sounds are compared to the syllables luhh, dup, the first
sound being low-pitched and prolonged, the second sound high
and sharp.

Thus the heart-sounds may be represented :

lubb, dup (pause), lubb, dup (pause).

The causation of the second sound is very simple, and
may be considered first. It is heard just over the second
right costal cartilage, i.e. the place where the aorta lies
nearest the surface.

It comes at the end of the systole, as determined by the
hardening of the apex of the heart, felt as the apex-beat,
and can be shown to be synchronous with the closure of the
aortic valves. It is in fact caused by the sudden shutting
and stretching of these valves that occur directly the heart
ceases to contract and to force blood into the aorta. If the
valves be hooked back (by means of a wire passed down a

214

PHYSIOLOGY

carotid artery) in an animal, the second sound disappears, and
is replaced by a murmur caused by the blood rushing back
into the ventricle at the end of the systole. The same dis-
appearance of the normal second sound is often observed in
cases where the valves are prevented from closing by diseased
conditions.

The pulmonary and aortic valves generally close simul-
taneously. In some cases however the aortic may close
slightly before the pulmonary, giving rise to a ' reduplicated
second sound.' The pulmonary element of this sound is best
heard over the second left cartilage.

Fig. 111.

>9

^

Dia

stolfi

o

o

Blood lowing

>ystoU

i —

]

in

0 auri

cles and

of

Sj

stole

of

vent:

icles

Aur-

V

mtric

es

Dia

4ole.

from

veins.

icles.

01 Oa 03 04 0 5 OG 0 7 0 8 0 0 10 Bees.

Heart Sounds

■ dup Liilib diip

Diagram of events constituting a cardiac cycle.

The first sound has probably a twofold origin, viz. from
the sudden closure of the auriculo-ventricular valves, and
from the contraction of the thick muscular wall of the
ventricle.

If the veins going to the heart be clamped, so that the
heart can no longer be distended with blood nor the valves
put on the stretch, the sound is altered in character l)ut not
abolished. The first sound may indeed be heard on listening
with a stethoscope to the beat of an excised heart. It is said
that two notes maybe detected in the first sound — a high note
of short duration due to closure of the valves, and a long low-
pitched note due to the muscular contraction. This muscular
element of the first sound has the same pitch as the sound

THE AVASCULAR MECHANISM 215

produced by voluntary contracted muscle, and therefore as
the resonance-tone of the ear.

This consideration prevents our arguing from the tone
that a cardiac contraction is a tetanus. As we shall show
later on, each ventricular contraction is analogous to a simple
muscle-twitch, and not to a tetanus.

By means of these sounds we are able to determine to a
certain extent the amount of time taken up by each phase of
the cardiac cycle. In a healthy man the heart beats about
seventy-two times per minute. So we may say that each
systole with its corresponding diastole (cardiac cycle) is
completed in about ^-^ of a second.

This time is divided up in the following way : — Systole of
auricle j-L- sec, systole of ventricle y\ sec, diastole y\ sec.

The relationship between the phases and heart-sounds is
represented by Fig. 111.

2'he Pressure in the Heart Cavities during a Cardiac

Cycle

We arrive at a clear idea of the events occurring during
the ventricular systole by a study of the endocardiac pressure-
curve.

There are several methods by which the endocardiac
pressure may be recorded. In one (Chauveau and Marey) a

Fig. 112.

Diagram of Maiey's cardiac ' sound,' consisting of a long tube
a b, terminating at one end in the ampulla ni, which is covered
with an elastic membrane. The side-piece c serves to indicate
the position of the ampulla after it has been introduced into
the vessels.

cardiac ' sound ' is put down the jugular vein into the right
auricle or ventricle, or down the carotid into the left ventricle.
The cardiac sound is a stiff tube, having an elastic bag or
* ampulla ' at the end that is to be inserted into the heart
(Fig. 112). The upper end of the tube is connected with a
tambour, which is a small round metal tray covered with
delicate elastic membrane. To the top of the membrane a

216

PHYSIOLOGY

writing lever is attached (Fig. 118). Any change of pressure
on the ampulla causes a corresponding movement of the lever
of tlie tamhoiir, which may be recorded on a moving smoked
sm'face.

Since this instrument is very easily set into vibrations, it
is often difficult to know whether a given rise or depression on

Fig. 113.

Marey's tambour, a, axis of lever ; b, metal tray covered with rubber
membrane, and communicating by tube / with free end of cardiac
sound.

the tracing is to be taken as of cardiac or instrumental origin.
Hence it is better to make the tambour very small, with thick
rubber so as to limit the movements, and to fill it with saline
fluid, which is also used to fill the tube connecting it to
the heart. This is the principle of Hiirthle's manometer
(Fig. 114). It is evident that the mercurial manometer would
be no good for this purpose, since the mercury column has far

Fig. 114.

Diagram to show construction of Hiirthle's membrane
manometer.

too much inertia to follow the rapid changes of pressure in
the ventricles.

By the introduction of a valve in the tube leading from
the manometer to the heart, it may be used as a maximum
or minimum manometer. If the valve permits fluid to go only
towards the heart, the manometer will indicate the minimum
pressure ever attained during the cardiac cycle. If it be
turned the other way, it will indicate the maximum pressure

THE VASCULAR MECHANISM

217

(Fig. 115). In the dog the maximum pressure in the left
ventricle may be 140 mm., in the right ventricle 60 mm., and
in the right auricle about 20 mm. Hg. The use of the mini-
mum manometer reveals the striking fact that, at some period
of the cardiac cycle, there is a negative pressure in the
ventricle ; that is to say, the mercury is sucked up in the
limbs of the manometer towards the heart. This negative
pressure may amount to 30 or 40 mm. Hg. in the left ventricle,
to 15 mm. in the right ventricle, and to 7 or 8 in the right
auricle.

If however we register the variations of endocardiac pres-
sure by means of a manometer which is sufficiently accurate

Fig. 115.

to manometer

max. valve

mm. valve

to heart

. Frank's valve. This is placed in the course of the tube between
heart and manometer, so that the latter may be used as a maximum,
minimum, or ordinary manometer according;- to the tap which is
left open.

to record the quick changes in pressure that occur in the
ventricle with each heart-beat, we get a curve like Fig. 116.
By registering this curve simultaneously with that of the
blood-pressure in the aorta, we may determine what events
are occurring during each phase of the curve. The auricular
systole in some tracings causes a small rise of endocardiac
pressure, represented by an elevation on the curve which
would occur before the ordinate 0. It generally lasts about
0*05 second. It is not represented in the curve reproduced
in Fig. 116. This is immediately followed by the ventricular

218 PHySIOLOGY

coiiiraction, which lasts from o to 2. From o to i the ven-
tricle is getting up pressure, so that at i the intraventricular
pressure is equal to the aortic pressure. This process takes
from 0*02 to 0'04 second. Directly the intraventricular pressure
rises above this point the aortic valves open and blood is
driven into the aorta. The outflow of blood lasts from i to 2,
about 0'2 second. At 2 the ventricle suddenly relaxes, the
period of relaxation occupying about 0*05 second. The flat
part of the curve is often spoken of as the systolic plateau,
and on an average occupies about 0'18 second. According to
the condition of the heart and peripheral resistance, this
plateau may present a gradual ascent or descent {v. Fig. 124).

Fig. 116.

Curve of intraventricular pressure, v, compared with pressure
in aorta, a. Each vibration of time-marker = jjy^ sec.
(Hiirthle.)

Almost immediately after relaxation commences the intraven-
tricular pressure falls below the aortic, so that the aortic
valves close somewhere near the upper part of the descent
(at 3).

Negative Pressure. — It will be noticed in the curve of endo-
cardiac pressure that the line drawn by the lever descends
slightly below the base line at the end of systole. This is the
period at which the negative pressure occurs. This is however
of such short duration that the most delicate manometers fail
to show its maximum value. Several explanations have been
suggested for the production of this negative pressure. "When
the flow of fluid through a tube is suddenly interrupted, the
column of fluid, which has a certain degree of inertia, tends
to go on, so that a negative pressure is produced in its rear.
If however the negative pressure in the ventricle were due to

THE VASCULAR MECHANISM 219

the sudden cessation of flow through the first part of the aorta,
we ought to obtain with the minimum manometer a negative
pressure at the root of the aorta equal to that found in the
ventricle. But this is not the case, so that the cause of the
negative pressure must be sought m the ventricle itself. It is
probably due to the fact that during ventricular contraction
the base of the heart, including the orifices of the pulmonary
artery and aorta, is constricted. Directly the ventricle relaxes,
the pressure of blood in these two trunks causes a dilatation
of their bases, and therefore of the base of the heart. This
dilatation of the base of the heart increases its capacity, and
so creates a negative pressure in the ventricular cavities.
This mode of production of the negative pressure may be
illustrated experimentally by connecting a manometer with the
interior of either of the ventricles of an excised heart, that has
ceased beating, and then forcing fluid into the aortic and
pulmonary arteries. With each distension of the arteries so
produced the mercury in the manometer sinks, showing the
production of a negative pressure in the ventricles.

It is possible also that the ventricles exert some expanding
force as they return from a contracted to an uncontracted
condition.

The Cardiac Impulse {Apex-heat)

The movement of the heart at each contraction is com-
municated to the chest-wall, over a limited area of which it
may be felt and seen, except in fat individuals. The region
whence the pulsation of the chest-wall is most marked lies in
the fifth intercostal space, a little to the median side of the
left nipple. The pulsation is often spoken of as the apex-beat,
and was formerly thought to be due to the twisting forward of
the apex at each systole, but really lies considerably above the
apex of the heart ; and as we have already seen, the apex, so
long as the pericardium is intact, is relatively motionless.

During diastole the ventricles form a flabby flattened
cone lying against the chest wall and slightly deformed by
the latter. In systole the ventricles contract forcibly on the
contained fluid, and become hard and rigid, assuming the
form of a rounded cone. This sudden recovery of shape and
hardening of the ventricular walls pushes out the part of the

220 PHYSIOLOGY

chest -wall in immediate proximity to the ventricles, and so
gives rise to the ' apex-beat.'

The cardiac impulse may be registered by means of a
cardiograph. In nearly all forms of this instrument a
button, resting on the chest-wall, transmits the movements of
the latter to a tambour, which again is connected by a tube
to a registering tambour. One such instrument is shown in
Fig. 117.

The curves so obtained, which are known as cardiograms,
may vary considerably in the same subject according to the
pressure employed and the exact spot at which the tambour

Fig. 117.

A cardiograph. This is strapped round the chest, the central
button is applied to the ' apex-beat ' and its pressure on the
chest-wall regulated by means of the three screws at the
sides. The tube at the upper part of the instrument serves
to connect the drum of the cardiograph with a registering
tambour such as that shown in Fig. 113.

is applied. Their interpretation often presents considerable
difficulties, owing to the fact that their form is conditioned by
two factors, viz. :

(1) The actual size (antero-pogterior diameter) of the
ventricles.

(2) The resistance to distortion {i.e. the tension) of the
ventricular wall. This factor will increase in importance
with increasing pressure of the cardiograph button on the
chest wall.

Fig. 118 represents a cardiographic tracing or cardiogram,
which may be spoken of as typical. In order to interpret
this curve, we must record at the same time either the intra-

THE VASCULAR MECHANISM

221

ventricular pressure in animals, or the heart-sounds in man.'
Applying the latter method we may obtain the curve shown
in Fig. 119. In this curve it will be seen that the first heart-

Cardiogram (Hiirthle

sound, corresponding to the ventricular systole, begins, not
at the commencement of the rise of the cardiogram, but at
the notch near the top of the ascent. From this fact we may

Fig. 119.

1 ■ 1

ifV. _ ,\r. - _ _

__P=^^

Cardiogram (r.) with simultaneous record of heart-sounds (a)
(Hiirthle). 1. Position of first heart-sound. 2. Position of
second heart-sound.

conclude that the first part of the ascent is caused by the
auricular systole forcing blood into the ventricle, the ventri-

' This mechanical record of the heart-sounds has been successfully
accomplished by Hiirthle. His method consists in an application of the
microphone. A special form of stethoscope is so arranged that by its means
the vibrations corresponding to the heart- sounds are transmitted to a contact
between silver and carbon. Through this contact a strong current is passing.
This also passes through an electro-magnet, which attracts an iron disc
attached to the membrane of a Marey's tambour. Any vibration transmitted
to the carbon-silver contact alters its resistance, and so the strength of the
current passing through the electro-magnet. In this way the heart-sounds can
affect the pull exerted by the electro-magnet on the membrane of the tambour,
and the change in the volume of the contained air is recorded by means of an
ordinary registering tambour.

222 PHYStOLOGY

cular systole 1)eing marked by the notch near the top of the
curve. In Fig. 118, taken from the dog, the auricular curve
is more distinct as a slight elevation preceding the rise due
to the contraction of the ventricles. Other forms of curve
however are often obtained, which show considerable differ-
ences from the endocardiac pressure, and are spoken of as
atypical. They are often conditioned by a faulty position
of the cardiograph.

THE VASCULAR MECHANISM 223

Section 8
THE PULSE

If the finger be placed on some artery, such as the radial,
we feel an expansion of it occurring at regular intervals
corresponding to the heart-beats. On the tracing of a mer-
curial manometer we saw a similar rise and fall produced
by each heart-beat. So the pulse may be defined as the
expansion of the artery under the increased blood-pressure
caused by each ventricular systole. Just as the blood-pres-
sure diminishes from heart to periphery, so the pulse
diminishes in size as we get farther away from the heart.
If the arterial system were perfectly rigid, the increased
pressure due to the forcing of blood into it by each ventri-
cular systole would occur almost simultaneously over every
point of it. In the elastic distensible arteries however, the
first effect of the inflow of blood into the aorta is to distend
a section of the aorta nearest to the heart. The elastic re-
action of this forces a portion of blood on into the next
section, distending it in its turn. And so the increased
pressure is transmitted from segment to segment of the
arteries, in the form of a wave, at the velocity of about five
metres per second. We must be careful not to confuse the
velocity of the pulse- wave with that of the blood. The
velocity of the blood in the aorta is not more than half a
metre per second, and gets less and less towards the periphery.
The pulse-wave may be compared to a wave produced by the
wind travelling rapidly down a sluggishly flowing river.

We will make this difference clearer by an illustration. If
the hindmost of a row of billiard balls be struck sharply with
a cue, the foremost ball flies off and the others stop still. In
this case the energy imparted to the first ball by the stroke
has been transmitted from ball to ball, just as the effect of the
ventricular contraction is transmitted from section to section
of the arterial blood-stream. If the balls are struck so that
the cue continues pressing on the hindmost after the stroke is
delivered, the front ball flies off", while the others move slowly
along in the direction of the stroke. In the arteries this

224 PHYSIOLOGY

continuous pressure is furnished by the elastic reaction of the
arterial wall, and we see how the impact of the blood may
travel quickly along as a wave of increased pressure, while the
blood itself is moving slowly along, impelled by the elastic
reaction of the arterial wall.

To study the pulse more fully it is necessary to obtain
a graphic record of the expansion of the arteries, or, what
comes to the same thing, of the exact changes in pressure
which produce this expansion. The curve obtained with the
mercurial manometer shows elevations corresponding to the
pulse ; but the instrument is far too sluggish to record the
finer variations of pressure. For this purpose a manometer
such as Hiirthle's, which has very little inertia, must be
used.

The expansion of the artery is registered by means of a
lever which may be made to rest more or less heavily upon

Fig. 120.

the artery, and the movements of which are recorded on a
blackened surface. Such an instrument is called a sphygmo-
grapli. Of the many forms of sphygmographs, Marey's or
Dudgeon's is perhaps the most convenient for clinical pur-
poses (Fig. 120).

The principle of Marey's sphygmograpli is shown in Fig. 120. The button
(b) is adjusted so as to press on the radial artery. Its movements are trans-
mitted to a lever (m). The screw on this works on a small cogged wheel at (o),
which is also the axis of the writing lever (1). The movements of the button
(b), thus transmitted to a point near the axis of (1), are reproduced by this
lever highly magnified, and as such are recorded on a blackened surface. The
pressure on the artery can be adjusted by means of the screw (s).

Dudgeon's sphygmograph (Fig. 121) is rather easier to use than Marey's,
and is therefore largely employed for clinical purposes. It is provided with
a dial by which the pressure on the artery can be graduated, and has a small
clockwork arrangement for moving along the slip of smoked paper on which
the records are taken. The arrangement of the levers in this form of sphyg-
mograph is shown in Fig. 122, where f is the (adjustable) spring bearing by its
button p on the artery. The up and down movements of p are transmitted
to s being much magnified and converted into side to side movements. The

THE VASCULAR MECHANISM

225

point of s rests on the blackened surface represented in section at a, and
scratches on this, when moving, a magnified record of the expansion of the
artery under the knob p.

Either form of sphygmograph is generally applied to the radial artery
since this is near the surface and is supported by bone, and the arm is well

Fig. 121.

Dudgeon's sphygmograph, showing its mode of application
to the radial artery.

adapted for the application of the sphygmograph. The pulse-curve obtained
by means of a sphygmograph varies according to the artery employed and the
force with which the lever presses on the artery, but all the curves present the
same general features.

Fig. 122.

Diagram of arrangement of recording lever in Dudgeon's
sphygmograph.

Fig. 123 represents a pulse-curve taken from the radial
artery.

It will be noticed that the elevation due to the expansion

15

22() PHYSIOLOGY

of the artery is sudden and uninterrupted. We have ah-eady
explained that this is due to the sudden pumping of blood
into the first part of the aorta, whence the impulse is trans-
mitted as a wave along the arteries. The curve descends
gradually till the next beat occurs, since the elastic reaction
of the arteries, which tends to keep up the pressure, acts
more constantly and steadily than the heart-beat. On this
descending part of the curve are seen two or three secondary
elevations, (b) is the primary or ' percussion ' wave, (c) the
predicrotic or ' tidal ' wave, and (e) the dicrotic wave. Eleva-
tions may occur on the curve after (e), which are called post-
dicrotic waves. It is better however, for reasons which
we shall see presently, to class the elevations before the
dicrotic notch (d) as systolic elevations, and those afterwards,
including the dicrotic elevation itself, as diastolic. For the

Fig. 123.

Pulse-curve from radial artery.

exact understanding of these elevations, it is necessary to
take simultaneous tracings of the pressure in the left ven-
tricle and the aorta. In this way we may dissociate the
waves caused by the ventricular systole from those having
their origin in the aorta. In Fig. 124 are represented typical
tracings of cardiogram, intraventricular pressure, and aortic
pressure taken simultaneously. The dotted lines are drawn
through synchronous parts of the curves. Considering first
the dotted part of Curve II and Curve IV,' we see that the
contraction of the ventricle begins at a ; the rise of intra-
ventricular pressure from a to b is without effect on the aortic
pulse ; at b the intraventricular is exactly equal to the aortic
pressure, and then rapidly rises above it. Since the aortic
valves offer no resistance to the flow of blood from ventricles

' Curve IV in Fig. 124 must be compared with the pulse-tracing taken
from the radial artery in Fig. 123. It will be seen that, apart from the fact
that Fig. 124, IV, is more lengthened out than Fig. 123, owing to the great
rapidity of the recording apparatus, the curves are practically similar.

THE VASCULAR MECHANISM

227

to aorta, they must open so soon as the intraventricular
exceeds the aortic pressure, and this is shown to be the case
by the rise of pressure in the aorta. From b to c the

See.

Fig. 124.

Svstolo

Diastole

Diagram (after Hiirthle) showing simultaneous cardiogi'aphic,
endocardiac, and aortic curves. I. Cardiogram. II. Endo-
cardiac pressure. III. Aortic pressure. IV. Aortic pressure,
corresponding to dotted endocardiac curve in II.

ventricle is still contracting and forcing the blood into the
already distended aorta, so causing a rise of pressure. At
c the ventricle relaxes, the intraventricular pressure falls

228

PHYSIOLOGY

quickly, and at d has fallen below the aortic pressure. The
aortic valves must now close, since the pressure is greater on
their aortic side. The fall of pressure in the ventricle now
goes on uninterruptedly, but in the aorta there is a sharp
elevation immediately after d. This elevation is the dicrotic
wave. We thus see that it comes immediately after closure
of the aortic valves.

There are several factors at work tending to produce a
secondary wave at this point.

If a column of fluid moving along a tube (a, b, Fig. 125)
provided with a stopcock (c) and a manometer (m) be suddenly
checked by turning the cock (c), the column in front of the
cock, having a certain momentum, will tend to go on moving,
and therefore produce a suction or negative pressure behind

Fig. 125.

"=17=*

it. This will be indicated by a depression of the level of the
manometer. The fluid will flow back to fill this partial
vacuum, and so a series of oscillations in the column, getting
smaller and smaller, are produced, which are recorded by the
manometer as oscillations of pressure. The same thing
must occur in the beginning of the aorta, when the inflow
of blood from the ventricle suddenly ceases with the end
of the ventricular contraction. In this case however the
oscillations are increased by the elastic reaction of the arterial
wall, just as a weight which is suddenly applied to a piece of
elastic swings up and down before it comes to rest with the
elastic in a permanent condition of tension. These two factors
combine in producing a negative wave in the beginning
of the aorta at the end of the ventricular systole, the
blood driven up against the aortic valves closing them tightly

THE VASCULAR MECHANISM 229

and putting them on the stretch. The negative wave, even
in the rigid tube, is followed Ijy a positive wave in the
opposite direction. In the aorta this positive wave is in-
creased by the elastic reaction of the stretched aortic valves,
so that we may regard the blood as being driven up against
them by the negative pressure, and then rebounding like
a billiard ball from the elastic cushion, to give rise to the
dicrotic elevation.

The post-dicrotic weaves, when present, are probably due to
the waves of oscillation.

We have now to consider the elevations in the first part
of the curve, which we have spoken of as systolic elevations,
and which include the pre-dicrotic elevation. It will be seen
that they are also represented on the ventricular curve, and
occur while the aortic valves are open and blood is flowing
from the ventricle into the aorta. They are probably due to
the elastic vibrations of the aortic wall, and perhaps of the
heart-wall itself, started by a sudden increase of tension in
the aorta and heart.

The general form of the pulse-curve varies with changes
in the heart, in the arteries, and in the peripheral resistance.
Thus some curves may present secondary elevations on the
ascending part, as in Fig. 124, III, and are called anacrotic,
while in others all secondary elevations occur on the descend-
ing part. This latter type is called Icatacrotic, and is the
tracing usually obtained from a normal radial artery. By
comparing these two types of curves with the corresponding
intraventricular pressures, we find that, in both cases, blood
is flowing into the aorta during the whole time from the
beginning of the primary elevation to the notch just before
the dicrotic elevation. This is shown by the fact that the
intraventricular pressure is all this time slightly higher than
the aortic pressure. So long as this is the case blood must
flow from ventricle into aorta. (This fact shows that there
is normally no part of the cardiac cycle during which the
ventricle remains contracted and empty, the ventricle in all
cases relaxing before it has completely emptied itself of
blood.)

Now it is easy to see the conditions which determine
whether the systolic plateau shall be ascending or descend-
ing, and therefore when the pulse shall be anacrotic or

230 PHYSIOLOGY

katacrotic. If, after the first sudden rise of pressure in the
aorta, the blood can escape more rapidly through the peri-
pheral resistance than it is thrown into the beginning of the
aorta, the systolic plateau will sink, and a katacrotic pulse
tracing is obtained. If on the other hand the peripheral
resistance is high, or an extra large amount of blood is
thrown into the aorta at each stroke of the heart {e.g. by pro-
longation of the diastole), the aortic pressure will rise so
long as blood is flowing in, and we get an ascending systolic
plateau and an anacrotic pulse. Thus we obtain an anacrotic
pulse in old people with Bright's disease, in whom the peri-
pheral resistance is very high, and also in animals when the
heart is slowed by vagus action.

The production of the dicrotic elevation is favoured by
any influence which increases the elastic resiliency of the
arteries or causes the primary elevation of the pulse to be
rapid and sharp. Thus it is much more pronounced in young
people than in old people, whose arteries have become rigid.
"Where the peripheral resistance is low through relaxation of
the arterioles, and the heart is beating forcibly, as in many
cases of fever and also to some extent after a good meal with
alcohol, the dicrotic elevation becomes very marked. Under
such circumstances it may be easily felt with the finger at the
wrist, and in many cases the mistake has been committed of
taking the dicrotic wave for a normal beat, and so doubling
the rate of the pulse.

In tracings of the artificial pulse obtained from the arterial schema,
secondary elevations are observed on the descending part of the curve, which
are not explained in any of the above-mentioned ways. These waves are the
reflections of the primary wave from the peripheral resistance. This is shown
by the fact that the nearer to the peripheral resistance we record the pulsation,
the nearer is the secondary to the primary wave. Near the pump the two
waves may be separated by a considerable interval (Fig. 126).

It has been thought that some of the elevations in the normal pulse-curve
could be explained as reflected waves. This theory is at once excluded by
the fact that wherever we take the pulse tracing, whether from the aorta,
carotid, radial, or dorsalis pedis, the secondary elevations are always situated
the same distance from the beginning of the primary elevation, showing that
all these waves are centrifugal, and have their origin in the beginning of the
arterial system.

Besides, a single reflected wave from the multitudinous peripheral divisions
would be impossible, as the reflected waves from any one part would be interfered
with and destroyed by the reflected waves coming from all the other parts. A
reflected wave would be increased by a high peripheral resistance, and not
diminished as the dicrotic wave is.

THE VASCULAR MECHANISM

231

sovWAAAArVAnA/V/X A AAA /

Pulse-curves described by a series of sphygmographic levers placed
at intervals of 20 cm. from each other along an elastic tube, mto
which fluid is forced by the sudden stroke of a pump. The pulse-
wave is travelling from left to right, as indicated by the arrows over
the primary (a) and secondary (b, c) pulse -waves. The dotted vertical
lines drawn from the summit of the several primary waves to the
tuning-fork curve below, each complete vibration of which occupies
J- sec allow the time to be measured which is taken up by the wave
in passing along 20 cm. of the tubing. The waves (a') are waves
reflected from the closed distal end of the tubing ; this is indicated by
the direction of the arrows. It will be observed that m the more
distant lever (VI) the reflected wave, having but a slight distance to
travel, becomes fused with the primary wave. (From Foster, after
Marey.)

232 PHYSIOLOGY

Venous Pulse. — Under certain conditions the pulse may be
carried on from the arteries through the capillaries into the
veins, giving rise to a venous pulse. Thus stimulation of
the chorda tympani nerve causes all the arterioles of the
submaxillary gland to dilate. The peripheral resistance is
in this manner so lowered that it is insufficient to destroy
the arterial pulse, and on cutting the veins from the gland
blood spurts intermittently from their peripheral end. Lower-
ing the resistance in this case has produced the same effect
as unclamping the tube c^ (Fig. 100) in the arterial schema.

On attaching a manometer to the central end of the
superior or inferior vena cava, elevations are observed
corresponding to the variations in the auricular pressure.
These are double for each heart-beat. While the ventricle
is contracting there is a slow rise, due to the fact that the
blood, which is flowing in from the veins, cannot escape into
the ventricle, and so distends the auricle ; a second short
sharp elevation of pressure is produced by the auricular
systole.

Alterations of venous pressure, determined by the respira-
tory movements, are also to be observed in the great veins,
the pressure sinking during inspiration and rising during
expiration. These may be spoken of as the respiratory venous
pulse.

THE VASCULAK MECHANISM 233

Section 4
CAEDIAC EHYTHM

If the heart be rapidly cut out of the body, it will con-
tinue beating in a normal fashion for some time— in the case
of mammals from five to ten minutes ; in the case of cold-
blooded animals, such as the frog or tortoise, for some hours or
even days. We say therefore that the rhythm of the heart is
automatic ; and we have now to discuss wherein this automatic
rhythmicity lies. The circumstance that the cold-blooded
heart goes on beating so long, when severed from all connec-
tion with the body, has caused it to be much used in investi-
gations on the subject, and from it most of our knowledge has
been acquired.

Methods of Investigation

The contractions of the frog's heart may be recorded by
magnifying its movements by means of a light lever, one end
of which rests upon the ventricle, while the other end is made

Fig. 127.

Schiifei's heart plethysmograph.

to write upon a blackened surface — or, as in Gaskell's method,
by clamping the heart in the auriculo-ventricular groove,
and attaching threads from auricle and ventricle to two
levers which are arranged to write one over the other. Or
we may register the changes in the intraventricular pressure
by allowing dilute blood or some other nutrient fluid to
flow through a perfusion cannula tied into the ventricle, and
attaching the exit-tube of the cannula to a small mercurial
manometer.

Another way is to register the changes in volume of the

234 PHYSIOLOGY

heart (Fig. 127). The ventricle is tied round a perfusion
cannula, and is inserted into an air-tight vessel containing
oil. On one side of the vessel is a tube, in which a lightly
moving piston is fitted, to which a writing lever is attached.
Fluid is passed through the heart by the perfusion cannula at
a constant pressure. The changes in volume are indicated by
the movements of the piston.

Anatomy of the Frog's Heart

The frog's heart differs anatomically in several respects
from the mammalian heart. It consists of sinus venosus, two
auricles, one ventricle, and bulbus arteriosus. The venous
blood from the body flows into the sinus venosus by the three

Diagram of frog's heart (after Cyon). V. Ventricle. E.A.,
L.A. Rijrht and left auricles (atrium). S.V. Sinus venosus.
P.V. Pulmonary veins. L.V.C.S. and R.V.C.S. Left and right
superior vena cava. V.C.I. Vena cava inferior. Tr.A. Truncus

arteriosus.

venae cavee, and thence into the right auricle. The left auricle
receives the blood from the lungs. The ventricle thus receives
mixed arterial and venous blood.

The muscular fibres of the heart are less highly developed
than those of the mammalian heart. They are spindle-
shaped, and only dimly cross-striated. The cross-striation
becomes more distinctly marked as we proceed from sinus
to ventricle, the sinus muscle-fibre representing the most
primitive condition. There is complete muscular continuity
between all the cavities of the heart. The circular ring of
muscle at the junctions of sinus with auricles, and of auricles
with ventricles, presents only slight traces of cross-striation.

The heart is well supplied with nerve-fibres and ganglion-
cells. The two vagi enter the sinus venosus, and branch just
under the pericardium. Here they become connected with a
collection of nerve-cells, spoken of as Remak's ganglion.

THE VASCULAE MECHANISM 235

From the sinus, the two vagi, now called septal nerves, pass
down in the interauricular septum, one in front and the other
behind. Near the auriculo-ventricular groove they enter two
collections of ganglion cells, called Bidder's ganglia. From
these ganglia non-medullated fibres are distributed to sur-
rounding parts of the auricle and to the whole of the ventricle.
In the upper third of the ventricle occur scattered ganglion-
cells attached to the nerve-fibres. These are quite absent in
the lower half or two thirds

The Automatic Contraction of the Frog's Heart

The frog's heart in the body, or when removed from the
body intact, beats regularly, the contraction starting in the
sinus, then travelling to auricles, ventricle, and bulbus. If
however the heart be removed by cutting it across the sino-
auricular junction, or if the auricles be functionally separated
from the sinus by a ligature round this junction (Stannius'
ligature), the auricles and ventricle stop dead in an uncon-
tracted condition (diastole) while the sinus goes on beating
regularly. After the lapse of a period varying from five
minutes to half an hour the detached part of the heart begins
to beat, at first slowly and then more rapidly, but never
attaining the rate of the sinus. The auricles beat first, and
then the ventricle.

If now the ventricle be cut away by an incision in the
auriculo-ventricular groove from the auricles, the latter go on
beating ; while the former, after a few beats due to the excita-
tion of the incision, stops still, and only after a considerable
time may begin again to contract very slowly.

On the other hand, a ventricle-apex preparation (that is to
say, the lower two thirds of the ventricle separated func-
tionally from the rest of the heart) never beats again under
normal circumstances. To single stimuli it responds with
a single beat, not with a series of beats as the whole heart
does.

If the lower third of the ventricle be separated functionally
in the living frog by crushing the ring of tissue between it
and the upper third, it never gives a spontaneous beat again,
although it is under the most normal conditions possible
in the circumstances. There is thus a descending scale of

236 PHYSIOLOGY

automatic power in the different parts of the frog's heart —
from the sinus, where it is highest, to the lower part of
the ventricle, where it is apparently absent. From this fact
it has been thought that the automaticity of the frog's heart
is dependent on the ganglia present in it. The contraction
was supposed to be started by impulses proceeding from
the sinus ganglion. If this were cut off, Bidder's ganglia,
or the scattered cells in the upper third of the ventricle,
could, it was thought, take up its task of originating impulses.
The muscle-cells under this hypothesis act as the servants of
the ganglion cells, just as the voluntary muscles wait on the
commands of the cells in the spinal cord and brain.

But we have evidence that the muscle-cells do not play
so subordinate a part as this in the heart, and that the larger
ganglia, at any rate, are of very little importance in initiating
the rhythm. Eemak's and Bidder's ganglia may, with care,
be excised without markedly interfering with the normal
rhythm or sequence of contraction. The ventricle apex may
be made to contract rhythmically if the pressure on its
interior be slightly increased, either by clamping the aorta in
the living frog, or by supplying a ventricle-apex preparation
through a perfusion cannula with diluted blood at a pressure
rather above the frog's normal blood-pressure. A strip cut
from the apex of the tortoise's ventricle may be made to
beat rhythmically, if it be hung in a moist chamber and
stimulated at intervals with weak induction-shocks. After
a time the strip begins to beat of its own accord, and beats
rhythmically for many hours.

It seems probable then that the automaticity of the heart
is inherent in its muscular tissue, the difference in the auto-
matic power of the various parts being dependent on their
different histological characters. The lowly differentiated
sinus-cell has high rhythmic power and a quick rhythm of
beat, but contracts feebly. The more highly differentiated
ventricle-cell has only slight rhythmic power, but beats for-
cibly, and is a good servant of the sinus. If all parts of the
heart had equal rhythmic power or the same rate of rhythm,
there would be no reason why any one part of thei heart
more than another should initiate the beat. As it is, the beat
always starts in the part beating with the greater frequency,
viz. the sinus. In some animals this difference of rhythmic

THE VASCULAE MECHANISM 237

power is less marked, and the contraction may start from
either end of the heart. Even in the frog, the heart-cavities
may be made to contract with a reversed sequence, i.e. in the
order of ventricle, auricles, sinus, by artificially stimulating
the ventricle at a rate exceeding the normal sinus rhythm.

Propagatio7i of the Wave of Contraction in the Frog's

Heart

The next question is : How is the excitatory process eon-
ducted from sinus to auricles and thence to ventricle? It
was formerly thought that this conduction was efiected

Fig. 129.

Ventricle

Tortoise's heart (after Gaskell) as it appears when suspended
for registering the auricular and ventricular contractions.
N, nerve-trunk with fibres connecting Kemak's and Bidder's
ganglia ; Cor. v, coronary vein.

through nerves. It has however been shown by Gaskell in
the tortoise's heart, where the nerve-trunks run apart from
the auricles from sinus to ventricle, that division of these
trunks causes no alteration in the rhythm of the ventricle. If
however the auricles be cut through, leaving the ventricle
attached to the sinus by the nerve-trunks, the sequence of
beats is utterly lost.

The auricles may be slit up by interdigitating cuts, by
which all nerve-trunks must infallibly be divided, and yet
the wave of contraction passes from the sinus over the auricles
round the interdigitating cuts to the ventricle.

There is a distinct pause between the contractions of
auricles and ventricle. This was supposed to point to the
intermediation of nerves in the transmission of the excitatory
process across the groove. The pause however is probably
due to the fact that the muscle-cells forming the auriculo-
ventricular ring are very slightly differentiated, and so con-

238 PHYSIOLOGY

tract and conduct slowly, i.e. this muscular ring presents
a partial * block.'

The auricles may be made to beat in two halves by merely
dividing the sinus half from the ventricular half, leaving them
connected by a very narrow strip of auricular wall. In this
way a block is produced at the cut. The sinus contracts,
then the upper part of the auricles. This is followed by a
distinct pause, during which the excitatory process is passing
the block. The ventricular half of the auricles then con-
tracts, followed by the ventricle and bulbus.

We may conclude that a normal contraction of the frog's
heart originates in the muscular wall of the sinus, and
travels as a wave from muscle-cell to muscle-cell, over the
auricles and ventricle ; the apparent pauses between sinus
and auricles and auricles and ventricle being due to the low
conducting power of the muscular tissue connecting these
cavities.

It will be seen from what we have already said that the
contraction of the heart is to be looked upon as a single con-
traction wave, propagated from one end of the heart to the
other, just as a wave of contraction passes along the sartorius
(though at much quicker rate and of shorter duration) when
this muscle is stimulated at one end.

So7ne Properties of the Cardiac Muscle

Contraction ahvays maximal. — In several points however
the properties of cardiac muscle differ from those of ordinary
striated muscle. Its automaticity and power of responding
rhythmically to continuous stimuli have already been men-
tioned. The height of contraction of a voluntary muscle is,
within certain limits, proportional to the strength of stimulus.
If the ventricle, rendered motionless by a Stannius' ligature,
be stimulated with a single induction-shock, it always re-
sponds with a maximal contraction, whether the stimulus
applied be minimal or maximal. There is thus no propor-
tionality in the heart between strength of stimulus and
height of contraction. The heart, if it contracts at all,
always contracts to its utmost. The height of the contrac-
tion is dependent on the condition of the muscle at the time,
but not on the strength of stimulus.

' Staircase ' phenomenon. — If the frog's ventricle has been
at rest for some time, a single contraction makes the heart

THE VASCULAR MECHANISM 239

more excitable and in a better condition. So if, in a Stannius'
preparation, we excite the ventricle with single induction-
shocks once in every 10 seconds, the first four or five con-

FiG. 130.

Group of pulsations showing ' staircase ' character.

tractions form an ascending series, each contraction being
rather higher than the preceding one.

Summation of stimuli. — In a similar preparation it is easy
to demonstrate the summation of stimuli, which was described
in dealing with unstriped muscle. If the ventricle of a
Stannius' preparation be stimulated with inadequate shocks,
it is found, on repeating these shocks at short intervals of
time, that they become adequate, and cause a contraction of
the ventricle. The subsequent contractions then show the
progressive augmentation just described as the ' staircase.'

Influence of tension. — Much the most important factor
affecting the strength of the cardiac contractions is the
tension of the muscle-fibres. Within certain limits the
energy of contraction of the cardiac muscle increases with
the tension {i.e. resistance to shortening) to which the
muscle-fibre is exposed. This effect can be seen when the
resistance to the outflow of blood from the heart is increased,
and the resistance is only experienced during the contraction
of the heart-muscle. It is much better marked however
if the alterations of tension take place before the contraction,
i.e. during the diastole. In this case we observe that
within wide limits the heart contracts more forcibly the
greater its distension during the diastolic period. This effect
of the initial tension on the force of the ventricular beats is
well shown in Fig. 131, representing tracings taken from the
frog's ventricle under increasing initial tensions. In this
case the heart was contracting isometrically, i.e. against
a strong elastic resistance, so that the curves are a true
representation of the actual energy displayed by the heart.
In all cases the heart was unable to expel any of its contents,
so that the difference in height of the curves is due solely to

240

PHYSIOLOGY

the varying tension of the fibres at the beginning of the con-
tractile process.

Of course if the initial tension be continually increased, we
finally arrive at a point at which this peripheral reactive
mechanism gives way ; the heart is unable to contract against
the great resistance and becomes permanently stretched and
damaged.

The refractory period. — At each contraction of the heart-
muscle there is a sudden decomposition of contractile mate-
rial which, so far at least as concerns the incidence of an
external stimulus, is maximal, i.e. complete. Directly this
has occurred a process of assimilation or re-formation
of contractile material starts. This lasts throughout the

Fm. 131.

Isometric contractions of frog's ventricle. The initial tension was
continually increased from curve 1 to curve 6, each increase of
tension causing a greater energy of contraction, (v. Frank.)

diastolic period, and the store of contractile material is at
its maximum just before the next contraction. We may in fact
compare the process to a bucket, into which a stream of
water is constantly flowing, and which tips up automatically
and empties out its contents as soon as the water reaches a
certain height. It is evident that the power of the heart-
muscle to contract in response to a stimulus (its irritability)
must be at a minimum immediately after the automatic dis-
charge, or decomposition, has taken place, and will con-
tinually increase from this point as the store of contractile
material grows, until it arrives at such a height that the
explosive discharge occurs spontaneously. Hence in each
cardiac cycle there is a period, known as the refractory

THE VASCULAR MECHANISM

241

period, in which stimuli applied to the heart have no eiTect.
This will be followed by a period in which a stimulus is
followed by an extra contraction, but with a prolonged latent

Fi.!. 132.

■MBWIi

■■■■

Tracings of spontaneous contractions of frog's ventricle, to show
refractory period. In each series the surface of the ventricle
was stimulated by an induction shock at e, as indicated by the
tracing of the signal. In 1, 2, and 3, this stimulus had absolutely
no effect, since it fell during the refractory period. In 4, 5, 6, 7,
the effect of the shock was to interpolate an extra contraction in
the series, the latent period (shaded part) gradually diminishing
from 4 to 7 (diastolic rise of irritability). In 8 the irritability
of the preparation was already considerable, and the latent period
inappreciable. The ' compensatory pause ' after the extra beat is
also well shown in 4, 5, 6, 7, 8. (Marey.)

period. Just before the next spontaneous contraction the

irritability is at its height, and the heart-muscle responds

with a contraction to a minimal stimulus. These facts are

well shown in Fig. 132.

16

242

PHYSIOLOGY

Bhythm of Mammalian Heart

So far as we know, the process of contraction in the
mammalian heart is essentially the same as in the frog's
heart. The contraction starts in the terminations of the
great veins, and travels thence over the am-icles. A pause
of about one-tenth of a second occurs, and then the ventricles
contract, the contraction starting at the base and travelling
thence as a wave to the apex.

The wave-like progression of the excitatory condition in
the ventricle can be well shown, as in the frog, by leading
off the base and apex of the exposed ventricle to the two
terminals of a capillary electrometer. We then get in many
cases a diphasic variation differing only in the shorter dura-
tion of its phases from that described for the frog's heart.
We can in fact (as was shown by Waller) by leading off from
the apex beat and right hand obtain a photographic record
of the variation of the heart in man. Fig. 133 represents

Fig. 133.

Hsi (to apex)

Acid (to base)

Pulse tracing
from caroMd

Electrical variation of human heart. (BayUss and Starling.)

the variation of the ventricles as obtained in this way. It
will be seen that the variation is triphasic, implying that the
excitatory change starting at the base of the heart extends
thence to the apex, but the contraction lasts longer at the
base than at the apex. The production of the curve is shown
by the following diagram (Fig. 134).

With a more delicate electrometer it is possible to record
also the electrical change due to the auricular contraction.
This has the appearance of a sharp spike immediately pre-
ceding the triphasic ventricular variation.

The only essential difference between the mammalian and
amphibian heart seems to lie in the comparative automaticity

THE VASCULAR MECHANIS3I

243

of the ventricles in the two cases, the mammalian ventricles
possessing much more automatic power than that of the frog.
If the ventricles be functionally separated from the auricles by
crushing the auriculo-ventricular groove, both parts continue
beating, but at different rhythms, the ventricular rhythm being
as a rule much slower than that of the auricles. Conduction
is probably effected, as in the frog's heart, by the inter-
mediation of the muscular tissue.

Fig. 134.

negative
base

excitatory
change

Diagram to show mode of production of electrometer curve in
Fig. 133. The primary ' negativity ' of the base (shaded
portion of lower diagram) causes a movement of the Hg
meniscus downwards (the acid being connected to the base).
Immediately afterwards the negativity spreads to the apex.
The whole heart is at same potential, and the meniscus
returns sharply. The excited condition then dies away, but
lasts longer at the base ; hence a second excursion of the
meniscus downwards, with a slow recovery.

Although ganglia occur in large numbers in the different
parts of the mammalian heart, it is possible to find consider-
able sections, especially near the apex of the ventricles, which
are quite free from ganglion-cells. Porter has shown that
such a strip of muscle may be kept alive for some hours by
perfusing it through a branch of the coronary artery with
defibrinated blood. Under these conditions the strip beats
with a regular rhythm, demonstrating the absolute sufficiency
of the muscular fibres for the initiation and propagation of the
contractile process.

244

PHYSIOLOGY

Section 5
INNEEVATION OF THE HEAET

The heart is supplied with nerves from two sources — the
vagi and the sympathetic. The fibres supplying the heart run
a sHghtly different course in the frog and in the mammal, such
as the dog.

Fig. 135.

. y^"^^^- ^3nql. Vagus

-Verl". I.

Vago-Symparhe-Hc

Subclav. at-r

Aorra

-Splanchn. n,
lnl•e&^. arf

N.VIII

N.IX.

Sympathetic chain of frog (right side) to show connection with
vagus nerve. The sympathetic ganglia with their branches are
black. Of the peripheral branches only the splanchnic nerve is
represented. (Modified from Ecker.)

The sympathetic fibres to the frog's heart leave the cord
by the anterior root of the third spinal nerve, pass through
the ramus communicans to the corresponding splanchnic
ganglion, and thence by the second ganglion, the annulus of

THE VASCULAR MECHANISM

245

Vieussens, and the first ganglion to the cervical sympathetic.
This runs up to join the ganglion trunci vagi, and thence the
fibres run down with the vagus nerve (Fig. 135).

r.Sp.Ac.

Diagram of cardiac inhibitory and accelerator fibres in the dog
. (from Foster). r.Vg. Roots of the vagus. r.Sp.Ac. Roots of the
spinal accessory. G.J. Ganglion jugulare. G.h.V. Ganglion
trunci vagi. Vg. Trunk of vagus nerve. C.Sy. Cervical sympa-
thetic. G.C. Inferior cervical ganglion. A.V. Annulus of
Vieussens. A.sb. Subclavian artery, n.c. Cardiac nerves. G.St.
Ganglion stellatum. D.2, D.3, D.4, D.5. Second, third, fourth, and
fifth dorsal spinal roots. G.Th. Ganglia of the thoracic chain.

In the dog, the sympathetic fibres to the heart leave the
spinal cord by the anterior roots of the second and third dorsal
nerves, run in the rami communicantes to the stellate ganglion,
and thence by the annulus of Vieussens to the inferior cervical

246 PHYSIOLOGY

ganglion. The cardiac branches containing these fibres run
from the stellate ganglion, the annulus, the inferior cervical
ganglion, and the trunk of the vagus to the heart.

The accelerator nerves are small meduUated fibres as they
leave the cord and pass along the anterior roots and white
rami communicantes to the stellate ganglion. In this ganglion
they end in connection with its cells, and a fresh relay of
fibres, which are non-medullated, carries the impulses on to the
heart. In the heart they are apparently distributed directly
to the muscular fibres, without the intervention of any more
ganglion-cell stations.

The effect of stimulating these two sets of nerve-fibres is
the same in the frog and mammal. In the frog, since the

Fig 137.

Vent.

Allll 1

ill !

piMwm'wninny

Tracing to show effect of stimulation of the vago-sjmpathetic
nerve on the frog's heart. The rhytlim is unaltered, but the
beats of auricle and ventricle are much decreased in size.
On ceasing the stimulation the beats become augmented.
(Gaskell.)

sympathetic fibres run down in the trunk of the vagus, it is
necessary, in order to obtain pure effects, to stimulate the
intracranial part of the vagus or the cervical sympathetic.
If the intracranial vagus be stimulated while the heart is
beating regularly, the heart stops at once in diastole, or it may
give one beat before stopping. If the stimulation be now dis-
continued, the heart after a little while begins to beat again,
at first slowly, and gradually comes back to the normal rhythm.
In many cases, if the vagus be stimulated repeatedly, a distinct
improving action on the beat is observed, i.e. the heart beats
more forcibly and rapidly when the stimulation is discontinued

THE VASCULAE MECHANISM

247

than it did at the commencement of the experiment. The
vagus is named the inhibitory nerve of the heart. This inhi-
bition may influence either the rhythm or the force of the
ventricular contraction, the different results being probably
dependent on whether the sinus is most affected, when the

Fig. 138.

A tracing similar to Fig. 137. In this case however the stimulation
caused complete stoppage (inhibition) of both auricular and ven-
tricular beats. (Gaskell.)

beats will be slowed, or the ventricle, in which case each beat
will be weaker. If only a weak stimulus be applied to the
vagus, the effect may be merely to weaken or slow the beats,
without causing a complete stoppage.

Fig. 139.

Blood-pressure tracing from carotid of dog (taken with Hiirthle's
manometer), showing effect of excitation of vagus (between the
arrows), o. Abscissa line of no pressure.

Stimulation of the sympathetic cardiac nerves has exactly
the reverse effect, causing increase in force or rate of the
heart-beats or both results at once. They are therefore said
to be both augmentor and accelerator nerves.

The augmentor fibres are much less easily tired than the

248 iPHYSlOLOGY

vagus fibres. Hence, if the vago-sympathetic of the frog be
stimulated, the first effect is inhibition due to vagus action ;
the vagus nerve-endings then tiring, the influence of the stimu-
lation of the accelerator fibres makes itself apparent, and the
heart, while stimulation is still going on, commences to beat
more rapidly and forcibly than it did before.

Stimulation of the vagus also lowers the conductivity of
the cardiac tissue, and, with a carefully graduated stimulus, it
is often possible to make a block between auricles and ventricle,
so that the latter responds only to every second auricular
beat. The accelerator fibres have the reverse effect. We
may make an artificial block between auricles and ventricle
by clamping rather tightly the auriculo-ventricular groove,
so that the ventricle beats only once to every two auricular
contractions. If now the accelerator nerves be stimulated the
block is removed, and the ventricle beats in normal sequence
to the auricles.

These two sets of fibres have exactly the same function
in the mammal (dog). Vagus causes slowing of rhythm,
depression of force and of conductivity ; accelerators cause
acceleration, augmentation, and improvement of conducting
power. Since however the beat of the heart is normally ruled
by the auricular beat,' we find that the action of these nerves
is much more pronounced on the auricles than on the
ventricles. This is illustrated by the fact that during pro-
longed vagus excitation the ventricles may begin to beat with
a rhythm of their own, while the auricles remain perfectly
motionless.

In many animals the vagus centre in the medulla exercises
a tonic or continuous inhibitory action on the heart. Thus
in the dog, section of one vagus causes a slight quickening
of the heart-beat {e.g. from 60 to 80 per minute). If now the
second vagus be cut, the heart -beat is markedly quickened,
and may occur 120 times in the minute. The effect of vagus
section is still more marked if the vagus centre in the medulla
be in a condition of increased activity, as after administration
of morphia, or during asphyxia.

' The rate of the ventricle is determined by the frequency of the excitation
arriving at it from the auricles. The strength of the beat depends on the initial
tension of the ventricular muscle, and therefore largely on the amount of blood
sent into the ventricle by the auricular contraction.

THE VASCULAE MECHANISM

249

The accelerators are further distinguished from the vagus
in the length of their latent period, which in the case of the
former is excessively long. The latent period of vagus
excitation in the mammal is considerably less than a second,
whereas that of the accelerators amounts to ten or even

Fi(i. 140.

liitaifcyliiMiiiM]

(itmfflttfflmtiff^

BBBSiBBfiB

Tracings of ventricular (upper curve) and auricular contractions (lower
curve). From xtoy the accelerator nerves stimulated. Lowest line
= seconds.

twenty seconds (Fig. 140). The effect of accelerator stimu-
lation lasts for an equal length of time after the stimulation
is discontinued.

Afferent Nerves of the Heart

Besides these efferent fibres going to the heart, there are
other fibres running chiefly in the vagus which serve to
carry afferent impulses from the heart to the nervous centres.
Some of their terminal branches ramify over the ventricle
(of the dog) immediately under the pericardium. We may
investigate their functions by stimulation of the central ends
of the divided nerves. They may produce one or more of
four effects :

1. Pain, as evinced by the movements of an animal not
fully under the influence of an anaesthetic (we should be more
correct if we said that stimulation of these nerves produced
reflex movement).

2. Eeflex inhibition of the heart. If one vagus be cut and
its central end stimulated, there is very often slowing of the
heart by reflex impulses which descend the other vagus.

3 and 4. Pressor and depressor effects. Stimulation of
these nerves may cause a reflex raising (pressor) or lowering
(depressor) of the blood -pressure.

250 PHYSIOLOGY

Cardio-inhibitory Centre

There is one little spot in the medulla, in the neighbour-
hood of the origin of the vagus nerves, stimulation of which
causes inhibition of the heart. If this spot be destroyed,
reflex inhibition of the heart can no longer be produced ;
hence it is spoken of as the cardio-inliibitory centre. The
afferent nerves from the abdomen and intestine seem to have
very close connections with this centre, so that reflex inhibi-
tion of the heart can be easily produced in the frog by tapping
a loop of intestine with the handle of a scalpel. This con-
nection explains to some extent the depressed condition of the
circulation in man in severe abdominal affections, such as
peritonitis.

When the blood-pressure is raised, as by a general con-
striction of the arterioles of the abdominal viscera, the
resistance to the outflow of blood from the heart is increased.
This factor by itself would tend to produce a stronger heart-
beat, without any accompanying slowing. Under normal
conditions however we find that the ' rate of the heart-beat
is in inverse ratio to the arterial pressure ' (' Marey's
Law'), a rise of blood-pressure causing a slowing of the
heart, and vice versa. This law holds good only if the vagi
are intact. The slowing consequent on rise of pressure is
probably conditioned by two factors : (1) the increased pres-
sure in the cranial cavity directly affecting the cardio-
inhibitory centre ; and (2) the action of the rise of pressure
on the endings of the vagus in the walls of the heart, stimu-
lation of these fibres by the increased tension causing a reflex
inhibition of the heart through the same nerve-trunk. Both
these effects would of course be abolished by section of the
two vagi.

Influence of Drugs on the Heart

The cardio-inhibitory centre is stimulated by digitaline and
morphine, so that the heart is slowed under the influence of
these drugs.

Muscarine stimulates the nerve-endings of the vagus. If
applied to the frog's heart, it causes gradual weakening and
slowing of the beat, and the heart finally stops still in dia-
stole. If a solution of atropine be now applied, the heart

THE VASCULAR MECHANISM 251

commences beating again. It is fomid that stimulation of
the vagus is now absolutely ineffectual in producing inhibi-
tion. Hence we argue that atropine paralyses the termina-
tions of the vagus in the heart. The same paralysis of the
vagus is produced in the mammal if atropine be injected into
the circulation. After administration of atropine, stimulation
of the sino-auricular junction (the so-called local inhibitory
centre) has no effect on the heart.

If nicotine be injected into the circulation or applied
directly to the heart, it first stimulates and then paralyses the
nerve cells to which the vagus fibres run, and which give oft'
the inhibitory fibres to the heart muscle. After this drug
therefore, although stimulation of the vagus trunk has no
inhibitory action (the impulses being blocked in the heart
ganglia), stimulation of the sino-auricular junction still causes
inhibition in consequence of direct excitation of the post-
ganglionic fibres.

Curare has a paralysing influence similar to that of
atropine, but only when applied in large doses.

Physostigmin has the same action as muscarine, and, as in
this case, its effect is removed by the application of atropine.

Adrenaline, the active principle of the medulla of the
suprarenal bodies, when applied directly to the isolated heart,
causes a considerable augmentation and strengthening of the
beat. When injected into the circulation, it produces a general
constriction of the l)lood-vessels and a consequent rise of
blood pressure, and this rise is accompanied by extreme slow-
ing of the heart brought about by stimulation of the vagus
centre.

Dilute alkalies (KHO, 1 in 20,000) cause the frog's heart
to stand still in a tonic contraction, the tone of the heart
gradually increasing till the beats are no longer visible on the
tracing.

Dilute acids have the opposite eft'ect, removing the tonic
contraction produced by alkalies, and finally causing a stand-
still of the heart in complete relaxation.

252 PHYSIOLOGY

Section 6
THE WORK OF THE HEART

The energy of the ventricular contraction is expended in
two ways : firstly, in forcing a certain amount of blood into
the already distended aorta against the resistance presented
by the arterial blood-pressure, which itself is directly con-
ditioned by the resistance in arterioles and capillaries ; and
secondly, in imparting to the mass of blood so thrown out a
certain velocity. Thus the energy of the muscular contraction
is converted partly into potential energy in the form of in-
creased distension of the arterial wall, and partly into the
kinetic energy represented by the momentum of the moving
column of blood. The work done at each beat may be cal-
culated from the formula :

W = QR ^ "^-^

2g

where W stands for work, w for the weight, and Q for the quan-
tity (volume in ccms.) of Ijlood expelled at each contraction. R
is the average arterial resistance or pressure during the outflow
of blood from the heart, and v is the velocity of the blood at the
root of the aorta. In this equation QR is the work done in over-
coming the resistance,' and - is the energy expended in

2 g
imparting a certain velocity to the blood.

We have already discussed the means whereby the average
pressure and velocity of the blood in the aorta may be
measured, and it remains only to determine the output of
the ventricles at each beat, in order to have at our disposal all
the factors necessary for the calculation of the work of the
heart. The measurement of the output presents considerable
difficulties. Stolnikow and Pawlow practically cut out the

' This expression QB is only approximately correct. Supposing the pressure
in the aorta at the beginning of systole is 50 mm. Hg. and at the end of systole
150 mm., the work could not be deduced accurately from the average pressure,
but would need a simple application of the integral calculus for its determina-
tion. The simple expression employed above deviates from the real value only
by about 10 per cent., and is therefore sufficiently accurate for our purpose.

THE VASCULAR MECHANISM

253

systemic circulation altogether, and caused the blood from the
left ventricle to traverse an instrument (current-measurer,
Strumaiclie) which recorded automatically the amount of blood
that went through it in a given time.

In Fig. 141, I and II are two cylinders containing accurately fitting floats,
bearing writing levers on their upper ends. Each of these communicates below
with two tubes, a and v, one of which is connected to the right carotid artery,
while the other is inserted into the superior vena cava. All the other branches
of the aorta, as well as the inferior vena cava, are ligatured. At the beginning
of the experiment, cylinder II is filled with defibrinated blood. This blood

Fig. 141.

Diagram of Stolnikow's instrument.

passes down the tube 2v into the right auricle, and so through the right
ventricle and lungs, where it is aerated, into the left auricle and ventricle. As
the heart continues beating, the left ventricle expels its contents into cylinder I, so
that the piston in I is rising while that in II is falling. As soon as cylinder II
becomes empty, the tubes 1v and 2a are released and the tubes la and iiv are
clamped. The left ventricle now expels its blood through 2a into cylinder II
while cylinder I is emptying itself through Iv into the right auricle. We thus
get two series of zigzag lines traced by the piston rods, and the frequency of the
zigzags is an expression of the output of the left ventricle in a given time.

This method suffers from the defect that the arterial pres-
sure, in consequence of the absence of external resistance, is
extremely low, so that the heart is throughout under highly

254

PHYSIOLOGY

abnormal conditiuns. It enjoys however the corresponding
advantage that K (the resistance), though low, is constant
throughout the experiment, and the work done by the heart is
therefore directly proportional to the output.

Better methods are those based upon the application of
the plethysmographic method to the heart in situ. We may
either, as in Tigerstedt's method, employ the pericardium

Fig. 142.

Diagram of Roy's cardiometer. On the right of the figure are the
two quarter spheres which are clamped on to the pericardium at
the root of the heart.

itself filled with oil or air as the oncometer, and register the
changes in the volume of the heart by connecting the cavity
of the pericardium with some form of piston-recorder, or we
may make use of Roy's cardiometer. This is a brass sphere
in three segments. The two quarter spheres (Fig. 142) are
applied round the base of the heart and clamped together,
the cut pericardium being attached to their constricted neck,
the third segment, a hemisphere, is then applied over the

THE VASCULAR MECHANISM 255

apex of the ventricles and clamped to the parts already in situ.
Attached to the centre of this hemisphere is a modified piston-
recorder, containing a piston working in oil, with which the
whole of the apparatus is filled. At a is a spring which can
be adjusted, so as to exercise a constant pull upon the piston,
and reproduce to some extent the negative pressure under
which the heart normally works. The piston-rod carries a
lever which writes on a blackened surface. The excursions of
this lever are proportional to the diminution in volume of the
heart at each systole, and tlierefore serve as a measure of the
output of the ventricles.

An attempt has been made to determine the ov;tput of the ventricles from
the time taken up in the total circulation. It was mentioned earlier that a
solution of methylene blue injected into the central end of the jugular vein
could be detected in the blood flowing from the peripheral end of the same
jugular, after twenty-seven heart-beats. This has been interpreted errone-
ously as equivalent to saying that the whole blood made the whole circuit
of the vascular system and therefore passed through the heart twice in
twenty-seven heart-beats. Thus we should have only to divide the quantity
of blood in man (5,000 grms. in a man of 65 kilos.) by 27, in order to arrive
at the output of each ventricle at each cardiac systole, i.e. about 185 grms.
It is evident however that the figure obtained by the methylene-blue method
merely represents the shortest possible time in which any given particle of
blood, taking all the short cuts which may be open, can travel round the whole
circulation, so that the true output of the left ventricle in man must be con-
siderably less than 185 grms., and is probably not more than one-third of this
amount.

From a direct determination by the cardiometer method of the output in
animals, Tigerstedt concludes that the output in man at each beat is probably
between 50 and 100 ccms. By other methods, Zuntz has come to the conclusion
that 60 ccms. represents the average output in man.

Accepting this last figure as correct, we have now all the data for the cal-
culation of the work of the heart.

Qll = 60 X 0-150 m. x 13-6 ' = 12'2-4 grammetres.

Taking the velocity imparted to the column of blood in the aorta as
I metre —

w v2 _ 60 X 0-5-
2"^? " 2T9-8' " ^'^ gi-ammetres.

It is evident that this latter factor is negligible, and that for all practical
purposes we may regard the work of the heart as proportional to the product of
the output and the average arterial blood-pressure.

Taking the average pressure in the pulmonaiy artery at 25 mm. Hg, the

' The specific gravity of blood is taken here as approximately equal to that
of water. If it be desired to allow for this, it would be necessary to divide the
product by 1-07.

256 PHYSIOLOGY

work of the j-'igld ventricle at each beat would amount to ahout 20 f,'ranmietres,
a total for the two ventricles of 140 grammetres per beat, which is equivalent to
about 14,000 kilogrammctres in the twenty-four hours.

We are now in a position to discuss the effect of various
conditions on the total work of the heart. We have seen
that this varies as w x E, so it is evident that any condition
which increases either or both of these factors will increase
the work done and vice versa. Thus on exciting the peri-
pheral end of the vagus, the heart is slowed, the diastole
prolonged, and the amount of blood expelled at each systole
increased. There is however a fall of mean arterial pressure,
and the increased output is not proportional to the diminished
frequency of the beat, so that the total output in any given
time is less than that occurring before or after the stimula-
tion. E and w being both diminished, the total work done
by the heart is lessened.

In dealing however with the effect of experimental or
pathological conditions on the work of the heart, it is im-
portant to remember the wonderful power of ' compensation '
possessed by this organ. In consequence of the augmentor
effect of increased tension on the cardiac muscle, we can
increase the resistance to be overcome by the heart to three
or four times the normal amount without altering in any way
the quantity of blood expelled at each beat. Thus we may
put a ligature round the pulmonary artery and gradually
tighten it, until the lumen of this vessel is reduced to a third
of its normal extent, without causing any material change
in the blood-pressure ; although, if we connect a manometer
with the cavity of the right ventricle, we find that the endo-
cardiac pressure rises to three or four times the normal
amount, in order to expel the proper quantity of blood into
the pulmonary vessels and so into the left heart. In this
case the increased tension acts upon the ventricular muscle
during its contraction. The same result is observed if we
augment the work thrown on the ventricles by increasing the
inflow of blood into them during diastole. This increased
diastolic volume of the heart may be brought about either by
pressure on the veins of the abdomen, so increasing the venous
flow into the heart, or by the injection of large quantities of
fluid into the circulation (Fig. 143), or by destroying the
aortic valves and allowing regurgitation to take place from

THE VASCULAK MECHANISM

257

the aorta during diastole. In either case, the work done by
the ventricles is increased, causing a rise of mean arterial
pressure in the first two instances, and preventing any fall
of arterial pressure in the last case. A large number of
similar experiments may be devised, but they all teach the
same lesson, viz. that, within very wide limits, the output of
the heart is independent of the resistance to the output.

Fig. 143.

Systole

Caitliometer tracing from clog's heart to show effect of hicreasing the
volume of circulating blood (hydremic plethora) on the total output
and the volume of the heart. Between the parts A and B, 30 c.c. of
warm normal salt solution were injected intravenously, and between
B and C, 20 c.c. more. It will be noticed that both the systolic and
the diastolic volume are increased, i.e. the heart is more distended
during diastole, and does not contract to its normal size in systole.
The contraction volume, and therefore the output, are very largely
increased. (Roy.)

In a fairly healthy individual, increased work thrown
upon the heart by injury or narrowing of the valvular
orifices does not necessarily result in fatigue and failure of
the heart-muscle, but this tissue may react just as skeletal

17

258 PHYSIOLOGY

muscle does to increased work by hypertrophy. Where this
hypertrophy is sufficiently developed, we say that the heart-
lesion is fully compensated, and such cases may continue for
years, without the subject being aware that there is anything
the matter with his heart. It is not easy to explain the
causation of this hypertrophy, though it is possible that one
factor in the increased growth of the tissue-cells may be
the increased lymph-flow, which is the result of activity in
muscle. The katabolic changes, which accompany activity of
muscle, cause a marked rise of osmotic pressure within the
muscle-fibres, which therefore swell up in consequence of im-
bibition of fluid from the surrounding tissue- spaces. Activity
thus induces increased supply of nutritive material to the
constituent elements of the active tissues.

THE VASCULAR MECHANISM 259

Section 7
INNEEVATION OF THE BLOOD-VESSELS

We have already mentioned that the chief resistance to
the flow of blood occurs in the arterioles and capillaries.
The greater part of this resistance is in the arterioles, and
is dependent on the continued contraction or tone of their
muscular walls. If the spinal cord of a dog be divided just
below the medulla, artificial respiration being kept up, the
blood-pressure in the carotid artery falls from 120 to 40 mm.
of mercury. This fall is not due to any action on the heart,
which goes on beating well. It is due to a relaxation of all
the arterioles, and also of the portal and perhaps other veins.
This relaxation causes a lowering of arterial pressure in two
ways. In the first place, the peripheral resistance is largely
diminished, and in the second place the total capacity of
the vascular system is increased. In consequence of this
increase in capacity, we find that section of the cord lowers
the pressure, not only in the arteries but also in all the veins
of the body.

This experiment shows that the tone of the vessels is
dependent on the integrity of their connections with some
part of the nervous system. If a section be made just above
the medulla, the blood-pressure remains high. If however
a certain part of the medulla be destroyed, the blood-pres-
sure sinks as low as if the cervical cord were divided.
Stimulation of the same part causes a great rise of blood-
pressure, due to increase in peripheral resistance. We learn
then that the continued contraction or tone of the small
arteries is provided for by a restricted region of the medulla,
which we call the vaso-motor centre. (The lower border of
this centre is about 4 mm. above the apex of the calamus
scriptorius, and its upper border about 4 mm. higher. It
apparently coincides in position with the antero-lateral nucleus
of Clarke.)

In this section we have to consider the means by which
the vaso-motor centre is able to control the calibre of the
blood-vessels, and therefore the blood-supply to various parts
of the body.

260 PHYSIOLOGY

In order to study the influence of the nervous system on
the distribution of blood in various parts of the body, it is
necessary to determine not only the local condition of the
circulation, but also the general blood-pressure ; since a
diminished flow of blood through any part might be pro-
duced either by a local constriction of the blood-vessels, or
by a fall of general blood -pressure. It is essential to be
certain that any local change which is observed in the circu-
lation is of local production and not a secondary result of
vascular constriction or dilatation in some other large area
of the body. For the registration of the mean arterial blood-
pressure, the mercurial manometer is most advantageously
employed.

In order to observe local changes in the circulation, several
methods may be adopted.

1. The simplest method is that of ocular inspection. In
many cases it is easy to tell by the colour of the organ or
part whether its blood-vessels are constricted or dilated. If
for instance the abdomen be opened and the splanchnic nerves
stimulated, the intestines will be at once observed to become
pale and anfemic, owing to this constriction of their vessels.

2. Since the temperature of the peripheral parts of the
body is considerably lower than that of the blood flowing
into them, it follows that their temperature must be in some
degree proportional to the amount of warm blood which
reaches them, and we can use the surface temperature of a
limb as an index to the changes in the circulation through
the limb. Thus if thermometers be tied between the toes of
the two hind paws of an animal and the right sciatic nerve
be divided, the thermometer on the right side will show a
higher temperature than on the left, owing to the vaso-motor
paralysis produced in the right leg by the section of the
nerve.

3. Changes in the calibre of the blood-vessels of any part
will alter the rapidity of the blood-flow through that part,
provided that there is no concomitant opposing change in the
general blood-pressure. These changes in velocity of the
blood might of course be investigated on the arterial side by
one of the methods already described. It is more convenient
however in most cases to carry out the experiment on the
venous outflow, the blood being prevented from coagulating

THE VASCULAR MECHANISM

261

in the course of the experiment by some artificial means, such
as the injection of leech extract, or the defibrination^ of the
circulating blood.

A convenient way of measuring the venous outflow is to
let the blood drop on a mica disc attached to a Marey's
tambour, from which a tube is carried to a registering
tambour. Every drop is recorded on a moving surface by a
little elevation of the lever of the registering tambour.

4. The volume of an organ is largely dependent on the
amount of blood contained within its vessels. "VVe can there-
fore judge of the nature of changes in the circulation through
an organ by taking a graphic record of its volume. For this
purpose we use an instrument known as a plethysmograph or
oncometer, of which many forms have been devised.

Fig. 144.

Diagram of oncometer.

Fig. 144 represents diagrammaticaily the structure of
Roy's kidney oncometer. This is a metal capsule, the two
halves of which are jointed together, and are accurately fitted
to one another except at (h), where a small hole is left for
the exit of the kidney vessels and ureters. A delicate animal
membrane (m) is attached to the rim of each half of the
oncometer, the space between this and the brass capsule being
filled with warm oil. The kidney (k) rests inside, supported

' In dogs and cats the blood may be rendered uncoagulable by drawing off
half the blood, defibrinating it, and reinjecting it into the circulation. This
process is repeated five or six times, when it is found that the blood is no longer
coagulable — a condition which lasts for many houi's.

262

PHYSIOLOGY

on the bed of warm oil, from which it is separated by the
membrane. The tube (o) leads from the cavity between the
brass capsule and membrane to the registering apparatus
or oncograph, represented in Fig. 145. Any swelling of

g:

i^

Fig. 145.

^W^

Diagram of oncograph.

to oncometer

the kidney will drive oil out of (o) into the oncograph, and
will thus raise the piston of the latter. The excursions of
the piston are recorded by the lever (1), wliich is arranged

Fifi. 146.

-dZTUaa

Diagram to show structure of a piston recorder (Hiirthle's pattern).
This instrument consists of an accurately turned vulcanite piston,
moving in a glass cylinder. To the piston is attached a light
counter-weighted lever. The piston moves very easily, has very
little tendency to swing on its own account, and gives excursions,
which are directly proportional to the changes of volume of air or
fluid in the attached oncometer.

to write on a })lackened surface. Plethysmographs for the
limbs and other organs have been constructed on a similar
principle.

A very simple form of air-plethysmograph has been devised by Schafer. A
box is made of vulcanite adapted to the size of the organ whose volume is the
object of investigation. In one side of the box there is a depression sufficient to
accommodate easily the vessels and nerves going to the organ. The oncometer
is covered by a glass lid, the connections being made air-tight by means of
vaseline. A glass tube is fixed in one corner of the box. This is connected by
a rubber tube with a piston recorder (Fig. 146) or a tambour. Every variation
in the volume of the organ causes a movement of air into or out of the

THE VASCULAR MECHANISM

263

oncometer, and thus gives rise to a corresiJonding movement of the lever of the
piston-recorder.

A plethysmograph must always be used in connection with
a blood-pressure manometer if we wish to investigate the
active condition of the vessels of the organ under considera-
tion. Fig. 147 will serve as an example to show the mode

Fig. 147.

Blood-

""^'^'"'^^^'V.-V.-v^

pressure

' ■ .

Kidney-

volume

A'' \ X — -f -

. . ,....,., . ■ \.. . . ..■ .. . . A . . . 1 1,. ,,-L

y

Simultaneous tracings of carotid blood-pressure and volume of kidney.
Between x and x the peripheral end of the divided 10th nerve was
stimulated. Time-marking = seconds. (Bi-adford.)

in which these two forms of instruments are employed for
the investigation of vascular conditions. The upper curve
is the carotid blood-pressure, recorded by means of a mer-
curial manometer. The lower is the tracing recorded by the
lever of an oncograph in connection with an oncometer, in
which the kidney of the animal is placed. At the point
marked with a cross on the tracing, the peripheral end of
the anterior root of the tenth dorsal nerve was stimulated.
It will be seen that this stimulation is followed by a slight
rise of general blood-pressure, but a marked shrinking of
the kidney-volume. The rise of blood-pressure shows us
that there must be somewhere a constriction of arterioles
giving rise to increased peripheral resistance, since the heart-
beat is obviously unaffected. An increased blood -pressure
would by itself tend to force more blood into the kidney, and
so would cause an expansion of the kidney.

264 PHYSIOLOGY

It is evident that there must be an active contraction of
the arterioles of the kidney, emptying this organ of blood,
and so causing it to diminish in size. If we had used the
oncometer alone, we should have been in doubt whether the
shrinking might not be due to failure of the heart's activity.
Again, without the oncometer we should only have known
that there was increased peripheral resistance in the blood-
vessels in some part of the body, but we should not have been
able to localise it.

This experiment has taught us already that stimulation of
certain nerves causes constriction of the arterioles in definite
parts of the body. This influence of nerves on the calibre
of the arterioles is still better shown in the ear of the rabbit.
If this be held up to the light, the arteries and veins can be
plainly seen. If now the sympathetic in the neck be divided,
the ear on the same side will instantly become redder and
warmer than the other, and on holding it up to the light,
all the vessels will be observed to be much dilated, and many
small vessels will be evident that could not previously be
seen. On stimulating the upper end of the cut sympathetic
the reverse effect is produced ; the vessels contract, and the
ear becomes once more cool and pale. In the same way
constriction of the vessels in the web of the frog's foot may
be observed under the microscope to follow stimulation of
the sciatic nerve. Similar experiments to these have shown
that the muscular walls of all the arteries in the body are
under the control of the central nervous system, and that
they are held in a condition of continued contraction or
tone under the influence of the vaso-motor centre. Division
of the spinal cord in the neck cuts off the arteries in the
trunk and limbs from the vaso-motor centre, and these in
consequence become dilated, and the blood-pressure falls.
Division of the cord in the dorsal region similarly causes
dilatation of the vessels in the lower limbs. If the animal
be kept alive • after this operation for some time, the vessels
recover their tone, but lose it again if the spinal cord be
destroyed. We see then that, although the chief vaso-
motor centre lies in the medulla, there are also subsidiary
centres in the cord, which are able, after a time, to take up
by themselves the work of regulating the condition of the
blood-vessels in parts of the body suijplied by the spinal

THE VASCULAR MECHANISM 265

nerves. The nerves that convey impulses causing constric-
tion of the arteries are called vaso-constrictors or vaso-
motors.

Course of the Vaso-constrictor Nerves

In investigating the course of the vaso-constrictor fibres
we have to determine

1. The origin of the fibres from the central nervous
system ;

2. The course of the fibres on their way to their peripheral
distribution on the blood-vessels ;

3. Their connections with nerve-cells.

The first two details can be found by stimulating various
nerves and nerve-roots in different parts of their course and
observing the effects produced on the local and general
circulation. The importance of the third heading is due to
the fact that the vascular nerves, like the visceral nerves
generally, do not have their last cell-station in the spinal
cord. The fibres carrying vaso-constrictor impulses, which
leave the cord, do not pass direct to the blood-vessels, but
come to an end in a peripheral collection of ganglion cells,
which may belong to the main chain of the sympathetic or be
situated more distally and belong to the group of collateral or
peripheral ganglia.

These fibres, as they leave the central nervous system, are
small medullated nerves. These come to an end in a gan-
glion, where a fresh relay of fibres starts and carries the
impulse on to the muscle-cells of the vessels. These post-
ganglionic fibres difter from the pre-ganglionic fibres in being
non-medullated.

The discovery of the exact ganglia, with which any given
set of nerve-fibres is connected, is rendered easy by the fact
that in many animals the sympathetic ganglion-cells are para-
lysed by nicotin (Langley). The nicotin may be painted on
the ganglion or may be injected into the blood-stream. The
first efi'ect of the drug is a powerful stimulation of the gan-
glion-cell, so that, if the drug be injected, there is an enormous
rise of blood-pressure owing to the universal vaso -constriction
that is produced. This stimulation gives place to a condition
of paralysis ; the blood-pressure falls below normal owing to
the cutting off of the peripheral vascular nerves from the

266 PHYSIOLOGY

vaso-motor centre. Stimulation of the pre-ganglionic fibre is
now without effect, although the normal results follow stimu-
lation of the post-ganglionic non-medullated fibre.

By these methods it has been determined that all the
vaso-constrictor nerves of the body leave the spinal cord by
the anterior roots of the spinal nerves from the first dorsal
to the third or fourth lumbar inclusive. From the roots
they pass by the white rami communicantes to the ganglia of
the sympathetic chain lying along the front of the vertebral
column. Here they take different courses according to their
destination.

The fibres to the head and neck leave by the first four
thoracic nerves, pass into the sympathetic chain through the
ganglion stellatum and ansa Vieussenii to the inferior cervical
ganglion, and up the cervical sympathetic trunk to the
superior cervical ganglion. Here they end, and the impulses
are carried by a fresh relay of fibres, which start from cells
in this ganglion and travel as non-medullated fibres on the
walls of the carotid artery and its branches.

The constrictors to the fore limb in the dog leave the
cord by the white rami of the fourth to the tenth thoracic
nerves. The fibres run up the sympathetic chain to the
stellate ganglion, where they all end in synapses round the
cells of this ganglion. The impulses are carried on by non-
medullated fibres along the grey rami of the sympathetic
to the cervical nerves which make up the brachial plexus,
and run down in the branches of this plexus to be distributed
to the vessels of the fore limb.

The constrictor impulses to the hind-limb in the dog arise
from the nerve-roots between the eleventh dorsal and third
lumbar roots. All the fibres end in connection with cells
in the sixth and seventh lumbar and first and second sacral
ganglia of the sympathetic chain, whence the impulses are
carried by grey rami to the nerves making up the sacral
plexus.

The most important vaso-motor nerve of the body is the
splanchnic nerve. This nerve receives most of the fibres
forming the white rami from the lower seven dorsal and
upper two or three lumbar roots, the latter fibres often
taking a separate course as the lesser splanchnics. The
fibres can be seen to pass through the sympathetic chain of

THE VASCULAR MECHANISM 267

the thorax without interruption and for the most part have
their cell-station in the large ganglia, especially the semi-
lunar ganglia, of the solar plexus, whence a thick meshwork
of non-medullated fibres is distributed along all the vessels
of the abdominal viscera. The area of the vessels innervated
by this nerve is so large, that section of this nerve on each
side causes a large fall in the general blood-pressure. This
fall is more marked in animals such as the rabbit and other
herbivora, in which the alimentary canal is proportionately
very much developed, and has consequently a very large
blood-supph\

Vaso-dilator Nerves

Since the arteries are in a constant condition of moderate
contraction, a dilatation might be brought about by a relaxa-
tion of this tone by an inhibition of the normal constrictor
impulses proceeding to the vessels from the vaso-motor centre.
We find however in many parts of the body evidence of the
existence of a nerve-supply to blood-vessels antagonistic in its
function to the vaso-constrictors. Thus, if the chorda tymjjani
nerve going to the submaxillary gland be cut, no change is
evident in the blood-vessels of the gland. But if its peripheral
end be stimulated, there is instantl}' free secretion of saliva
from the gland, and all the blood-vessels are largely dilated.
In consequence of this dilatation the blood rushes through
the capillaries so quickly that it has no time to lose much of
its oxygen ; the blood flowing from the vein is therefore
bright arterial in colour, and is increased to six or eight
times the previous amount. If atropin be injected into the
animal, the action of the chorda tympani on the blood-
vessels is unaffected, although the secretion on stimulation
is abolished. The chorda tympani is therefore said to con-
tain vaso-dilator fibres for the vessels of the submaxillary
gland. Other examples of vaso-dilator (or dilatator) nerves
are the small 2^etrosal nerve to the parotid gland, the lingual
nerve to the blood-vessels of the tongue, and the nervi
erigentes or pelvic visceral nerves to those of the penis. It has
been thought that all the vessels in the body have a double
nerve-supply, vaso-constrictor and vaso-dilator. The presence
of the latter variety in a mixed nerve is often difficult to
prove, since on ordinary faradic stimulation the constrictor

268

PHYSIOLOGY

effect is always more pronounced. Moreover the dilators
do not seem to conduct any tonic influences to the vessels.
Hence, after section of a mixed nerve, the only effect
observed is that due to the removal of the tonic constrictor
influences, and the vessels in the area of distribution of the
nerve are therefore dilated. Two methods however have been
made use of to demonstrate the existence of vaso-dilators in
a mixed nerve-trunk.

(rt) If the sciatic nerve be cut, the vessels of the leg and
foot dilate. This paralytic dilatation passes oft' after two or
three days, and the vessels resume their normal calibre. If
now the peripheral end of the sciatic nerve be stimulated,
dilatation of the vessels is produced (Fig. 148 b). It seems

Fig. 148.

/

Nerve freshly divided.
Constriction.

Nerve 4 days degenerated.
Dilatation.

Pletliysmograpliic tracing of hind limbs, showing effect of stimu-
lating the sciatic nerve on the volume of the limb, a, immediately
after section of the nerve ; b, 4 days after section. The nerve
was stimulated between the two vertical lines. Curves to be read
from right to left. (Bowditch and Warren.)

that the degenerative processes affect the constrictor fibres
earlier than tlie dilator fibres, so that at a certain period after
nerve-section the latter alone respond to stimulation.

{h) If a mixed nerve be stimulated with shocks slowly
repeated at intervals of one second, instead of with the
ordinary faradic current, vaso-dilator effects are often obtained,
whereas stimulation of the same nerve with the faradic
current produces vaso-constriction (Fig. 149). Thus rapid
stimulation of the anterior root of the tenth dorsal nerve in
the dog produces shrinking of the kidney from contraction
of its blood-vessels. If the same nerve be rhythmically
stimulated with single shocks repeated at slow intervals, the
kidney swells, showing that its vessels have dilated.

The course of the typical dilator nerves differs very much

THE VASCULAR MECHANISM

269

from that of the constrictors. Instead of leavmg the central
nervous system in a particular area, and running through the
sympathetic chain before proceeding to their destinations, it
seems that the dilators may leave the brain or cord by any
cerebro-spinal nerve. Thus the chorda tympani springs from
the root of the facial nerve, the nervi erigentes from the

Fig. 149.

I per sec.

4 per sec.

16 per sec.
64 per sec.

Effect on the volume of the hind hnibs of the cat of stimulating the
sciatic nerve with induction shocks at different rates. It will be
noticed that with one shock per second, there is hardly any con-
striction but considerable dilatation, whereas with 64 shocks per
second the only effect produced is vaso-constriction. Curves to
be read from right to left. (Bowditch and Warren.)

second and third sacral nerves. All these, however, are probably
interrupted in a ganglion or collection of nerve-cells before
reaching their destination. Although in some cases, as in the
case of the vaso-dilators to the lips and gums of the dog, these
cell-stations may be situated in the sympathetic chain (stellate
ganglion), in the best marked vaso-dilators, such as the chorda
and nervi erigentes, there is no connection at all with the

270 PHYSIOLOGY

main chain of the sympathetic. The nerve-cells of the chorda
tympani lie buried in the hilum of the submaxillary gland,
while the vaso-dilators of the pelvic nerve are connected with
cells in the so-called pelvic ganglion and distributed over the
base of the rectum and bladder.

The so-called dilator nerves to the limb vessels seem to be fundamentally
different from the typical vaso-dilators just mentioned. It has been shown by
Bayliss that these nerves have their trophic centre in the spinal root ganglia, and
are apparently identical with the afferent nerves of the limbs. Mechanical
or electrical stimulation of the peripheral end of a cut posterior root, taking part
in the formation of a limb plexus, gives rise to well-marked vascular dilatation
of the limb vessels, especially those of the skin.

There is a striking analogy between the nerves distributed
to the blood-vessels and those going to the heart — which is
indeed only a specialised part of the general blood -tubes of the
body. These nerves, according to their action on the meta-
bolic activity of the tissues supplied, are divided by Gaskell
into anaholic and katahoUc nerves.

The anabolic nerves, as indicated by their name, cause
a building up or regeneration of the contractile tissue. They
therefore act as inhibitory nerves, and bring about a condition
of rest in the tissue. This class of nerves would include the
vagus and the vaso-dilator fibres.

The katabolic nerves cause an increased activity of the con-
tractile tissue and, as was shown in treating of voluntary
muscle (p. 132), active contraction is associated with and
derives its energy from a disintegration or katabolism of the
complex and unstable muscle molecule (inogen). An ordinary
motor nerve to a muscle is therefore a katabolic nerve. This
class would include the accelerator nerves to the heart and
the vaso-constrictors. The course of these two sets of nerves
bears out this comparison, the path taken by the accelerator
nerves being identical at first with that of the vaso-constrictor
fibres to the head and neck.

Beflex Alterations of the Blood-vessels

Life is reaction ; every vital act is a reaction of the
organism to changes in its environment. Hence we have
not completed our view of the changes affecting the vessels
until we have not only considered the means by which the
nervous system acts on the vessels, but also the means by

THE VASCULAR MECHANISM

271

which the centres are excited to action. In fine, we must
complete the reflex arc affecting the vessels by considering the
afferent impulses to the vaso-motor centre.

The afferent impulses to this centre may be divided into
pressor and depressor ; and these names are also applied to
the nerves that carry such impulses.

There is in the rabbit, cat, and horse a small nerve in the
neck that runs up from the heart to join the vagus or its
superior laryngeal branch. If after section of both vagi (to

Sup-, lar. n. J

Depressor

«

sec.

Sup-, lar. n.-^

---S

ymp.

, -Vagus

RABBIT

--- Sup-. Cerv. Gang.
-Depressor
Cerv. symp. n.

Vago. symp.

DOG

Diagrams of the connections of the depressor nerve in the rabbit
and dog, according to Cyon. It will be noticed that in the latter
animal the depressor nerve runs in the vagus trunk for the greater
part of its course.

prevent reflex inhibition of the heart) this nerve be cut and
its central end stimulated, while the blood -pressure is being
registered by means of a mercurial manometer connected with
the carotid artery, a marked fall of blood-pressure is at once
observed (Fig. 151). This fall of pressure is hardly notice-
able after section of the splanchnic nerves, showing that the
stimulation of the depressor has affected the vaso-motor centre,
inhibiting the constrictor impulses that normally pass down
the splanchnic nerves.

The splanchnic dilatation that is brought about by excita-
tion of the depressor nerve may be demonstrated by enclosing

272 PHYSIOLOGY

any organ of the abdomen in a plethysmograph. Fig. 152
represents a curve of the splenic volume, and shows the marked
expansion, together with fall of general blood-pressure resulting
from stimulation of the depressor nerve.

All sensory nerves are pressoj- nerves, i.e. stimulation
of their central end causes a marked rise of blood -pressure
in animals under curare and morphia. Thus a rise of the
general blood-pressure follows stimulation of the central end

Fig. 151.

Blood-pressure curve from rabbit showing effect of excitation of
central end of depressor nerve (mercurial manometer). (Bayliss.)

of the cut sciatic or superior laryngeal nerves (Fig. 153).
This rise of pressure is due to constriction of the arterioles,
especially in the splanchnic area. The effect however of
excitation of a purely sensory nerve is not quite so simple as at
first appears. In many cases stimulation of the central end
of a sensory nerve causes general arterial constriction with a
rise of blood-pressure, and at the same time a vaso-dilatation
in the area of distribution of the nerve. This can be demon-
strated by exciting the central ends of the posterior roots of
the nerves to a limb, which causes a swelling of the limb due

THE VASCULAR MECHANISM

273

to dilatation of its vessels, accompanied by rise of general
blood -pressure owing to constriction of vessels in the splanch-
nic area and elsewhere. The physiological purpose of this

Fig. 152.

B.P,

Spleen

Simultaneous tracing of arterial blood-pressure and splenic volume
fi'om a rabbit, showing the marked swelling of the spleen asso-
ciated with fall of general blood-pressure on stimulation of the
central end of the depressor nerve. The nerve was excited
between a and b. (Bayliss.)

arrangement is obvious. Thus when a limb is injured and
inflamed, and a good supply of blood is required for reparative
processes, the stimulation of the sensory nerves in the injured

Fig. 153.

Blood-pressure curve from carotid of dog. Between the arrows the
central end of a sensory nerve was stimulated (Hiirthle's mano-
meter).

area calls forth reflexly a dilatation of the blood-vessels in this
area. This dilatation alone allows an increased flow of blood
through the part ; but this flow is still further increased by

]8

274 PHYSIOLOGY

the rise of blood-pressure which is caused by the general
arterial constriction also induced reflexly by the stimulation
of the same nerve.

Factors influencing the Vaso-motor Centre directly.
Asphyxia

In addition to its power of response to the effects of peri-
pheral stimuli, the vaso-motor centre in the medulla may also
react to changes occurring in the blood with which it is supplied.
Thus administration of digitalis or strophanti! us to an animal
causes a marked rise of general blood-pressure due to the
constriction of the peripheral vessels and brought about by
impulses from the centre.

The changes occurring in the blood-pressure in asphyxia
are important, and depend partly on the abnormal stimulation
of the vaso-motor and vagus centres by the venous blood, and
partly on the affection of the heart itself. These phenomena
are best observed in a curarised animal, and we will first
consider them with both vagi cut, in order to shut out the
action of the vagus centre. The blood-pressure is registered
by means of a mercurial manometer in connection with the
carotid artery. On leaving off the artificial respiration, the
blood -pressure remains at the same height for twenty or
thirty seconds, the only change noticed being the absence of
the respiratory oscillations. At this point the blood-pressure
suddenly rises rapidly, and in another ten seconds may reach
a height twice as great as it was previously. The heart beats
a little more forcibly in consequence of the increased cardiac
tension, but its frequency is almost unaltered. The blood-
pressure remains at this height for about a minute, and then
gradually falls, the heart-beats becoming smaller and smaller,
until the pressure has sunk to a point very little above the
abscissa line (level of no pressure). This fall in pressure is
due to the failure of the heart. The heart, badly supplied
with oxygen, cannot overcome the enormous resistance pre-
sented Iby the contracted arterioles ; it gets over-filled, and
gradually loses the power of expelling any of its contents. If,
when the blood-pressure has sunk to its lowest point, the
heart be rapidly cut out of the body, it will at once begin to
beat fairly forcibly, being relieved of the excessive internal

THE VASCULAR MECHANISM 275

tension. The vessels however remain constricted until the
death of the animal. This is shown by two facts. If, while the
pressure is sinking, artificial respiration be recommenced, the
heart supplied with oxygen at once begins to beat more forcibly,
and the blood-pressure may rise to an even greater height
than immediately after the commencement of the asphyxia.
Again, if the volume of the kidney be recorded by means of
the oncometer, the rise of general blood-pressure produced by
asphyxia is seen to be accompanied by a marked shrinking of
the kidney, and this shrinking endures until the animal dies.

Fig. 154.

Vwv^V

Curve of blood-pressure tracing during asphyxia. The tracing was
taken by a manometer connected with the femoral artery of a
dog under curare. Artificial respiration discontinued at X. Both
vagi had been previously divided.

showing that the fall of blood-pressure following the rise is
due not to a giving way of the arterial resistance, but solely
to a failure of the heart. ^

If in the dog, and to a less extent in other animals, the
vagi be left intact, the blood-pressure tracing during asphyxia
has quite another appearance. At the point of the tracing
corresponding to the rapid rise in the previous experiment,
there is in this case only a slight rise of pressure, but the
heart begins to beat very slowly. At each beat it necessarily

^ There are no grounds for the statement sometimes made that constric-
tion of the lung arterioles plays any part in this fall of blood-pressure. The
increased distension of the right side of the heart after asphyxia by ligature
of the trachea is due to the thinner walls and greater distensibility of this
side of the heart, and to the fact that the forced respiratory movements tend
to fill the lung-vessels and the great veins, and so affect chiefly the right
heart.

276

PHYSIOLOGY

sends out a greater volume of blood than when it is beating
more frequently, and hence the oscillations on the blood-pres-
sure curve caused by the heart-beats become very large. This
slow beat is due to the action of the vagus centre which is ex-
cited by the venous blood, and it is at once abolished by section
of the two vagi. The sparing of the heart by means of this
vagus action enables it to last longer, and the final fatal fall
of blood-pressure due to heart failure comes on rather later
than when the vagi are divided.

During the period of increased pressure, waves are often
observed on the blood -pressure curve, which must arise in a

Fig. 155.

Blood-pressure tracings showing Traube-Hering curves. (C. J. Martin.)

slow rhythmic variation of the constrictor impulses sent out
from the vaso-motor centre. These waves are known as the
Traube-Hering curves, and are not to be confused with the
waves on an ordinary pressure-curve due to respiration, being
much slower in their rhythm than the latter. They are
observed not only during asphyxia, but may occur in blood-
pressure tracings from normal dogs, and are frequent in dogs
poisoned with morphia. Fig. 155 represents tracings obtained
from a dog under the influence of morphia and curare. The
upper curve, taken while artificial respiration was being carried

THE VASCULAR MECHANISM 277

on, shows the three forms of curves — the oscillations due
to the heart-beat, next in size those due to the respiratory
movements, which in their turn are superposed on the slow
prolonged curves, i.e. the Traube-Hering curves. The lower
curve is taken immediately after cessation of the artificial
respiration, and shows only the heart-beats and the Traube-
Hering curves.

The presence of Traube-Hering curves may generally be ascribed to a state
of abnormal excitation of the vaso-motor centre. This excitation may arise in
various ways. A very frequent cause is the one just described, viz. increased
venosity of the blood supplied to the centre. Well-marked Traube curves are
often observed in cases of hfemorrhage. In spite of the loss of blood, the vaso-
motor centre at first maintains a normal arterial blood-pressure by means of
vascular constriction. As the bleeding continues, this means becomes inade-
quate, and at this point the efforts of the centre take on a rhytlimic character,
giving well-marked Traube curves, just as the arm of a man holding up a weight
begins to shake before he is obliged to give way through fatigue. If the bleeding
still continues, the pressure sinks steadily and the curves disappear. The
curves may also be often observed during operations involving exposure of the
cord, and may possibly be ascribed in this case to abnormal irritations ascending
the posterior columns.

Spinal Vaso-motor Centres

As already mentioned, the spinal cord contains a series of
subsidiary vaso-motor centres presiding over the local vascular
reactions of the different segments of the body. If an animal
be kept alive by means of artificial respiration for some hours
after division of the cord just below the medulla, these centres
gradually resume their tonic influence, and the blood -pressure
slowly rises. If, after two or three hours, artificial respiration be
discontinued, the asphyxia excites the centres of the cord, just as
it does those of the bulb in the normal animal. The motor dis-
charge reveals itself however in a single prolonged spasm, not
in a series of convulsions as is the case when the connections
of the bulb are intact. At the same time a universal constric-
tion of the blood-vessels occurs, which outlasts the spasm of
the skeletal muscles and causes a very considerable rise of
blood-pressure {v. Fig. 155a).

Peripheral Vascular Beactions

Even after destruction of all connection with the central
nervous system, the blood-vessels still possess considerable
powers of maintaining a tone, and adapting themselves to

278

PHYSIOLOGY

changed conditions. Like all muscular tissues, the arterial
wall is largely influenced by tension — increased tension acting
as an excitant to increased contraction. Hence increased
blood-pressure will cause contraction of the arterial wall, while

50-=

lOSECS.

Blood pressure tracing taken by a mercurial manometer from carotid
artery of a dog, three hours after section of the cord, just
below the medulla oblongata. At o the artificial respiration
was discontinued. A general spasm of the skeletal muscles
occurred between x and x . The muscles then relaxed, and
were flaccid during the rest of the rise of blood-pressure.

diminished blood-pressure will cause relaxation — a state of
things eminently adapted to the maintenance of a continuous
flow of blood through a part, whatever may be the alterations
of general blood-pressure conditioned by changes occurring in
other parts of the body.

Influence of Gravity iipon the Circulation.

In dealing with the mechanics of the circulation we spoke
of a mean systemic or general blood-pressure. By this term
we imply that the vascular system under normal circum-
stances is always slightly distended, even if the blood is at
rest. The effect of the heart-beat is, by pumping blood from
the venous to the arterial side, to depress the pressure in the
veins below the mean pressure, and to raise that in the arteries
above the mean pressure. On account of the much greater
distensibility of the veins, the fall of pressure on the venous
side is not nearly as marked as the rise of pressure on the
arterial side. This mean systemic pressure probably amounts
in the dog to about 10 mm. Hg. It is difficult to measure

THE VASCULAR MECHANISM 279

it with accuracy, owing to the fact that any cessation of
the blood-flow, as by stoppage of the heart-beat, will tend
indirectly to alter the state of contraction of the blood-vessels,
and therefore the tension on the vascular walls.

Owing to the distensibiHty of the vascular system, the
pressure at any part, and the circulation as a whole, must
be largely dependent on the influence of gravity. If we take
a continuous tube of soft rubber and fill it with fluid to a
pressure of 10 mm. Hg., so long as the tube is horizontal the
pressure on its walls will be the same throughout its whole
circuit. If however the tube be hung up, the weight of the
fluid will tend to bulge out the lower dependent parts of
the tu])e, so that the upper part may be entirely collapsed
and empty. The vascular system, being also distensible,
would behave in a similar manner, if the state of contraction
of its walls remained unaltered during changes of position.
In man in the upright position the pressure in the femoral
artery is 45 mm. Hg. higher than the pressure in the carotid
artery. If there is paralysis of the blood-vessels, as occurs
during administration of chloroform, or to a lesser degree as
the result of illness, this increased pressure in the lower part
of the body, including the abdomen, which ensues on change
from a horizontal to a vertical position, may cause such a
bulging of these vessels that they accommodate the greater
part of the blood in the body. An insufficient amount is
therefore returned to the heart, and fainting ensues from
anaemia of the brain. In the normal individual the effects of
change of position are at once compensated for by a change
in the distensibiHty of the vessels, chiefly of the abdomen.
These become more rigid in consequence of vaso-constrictor
impulses arriving at them from the bulbar centres, and
accommodate therefore no more blood than they did in the
horizontal position at a lower pressure. If, from any reason,
this compensatory action of the vaso-motor centre is im-
perfectly carried out, the brain is insufficiently supplied with
blood and the respiratory centre is also set into increased
activity. The increased respiratory movements thus set up
act as a respiratory pump, the contractions of the diaphragm,
alternating with strong expiratory contractions of the abdo-
minal muscles, serving to support the yielding abdominal
vessels and to drive their contents on into the heart.

280 PHYSIOLOGY

Section 8
THE CAPILLARY CIRCULATION

The capillaries may be regarded as the chief part of the
circulation, since the whole object of the varied arrangements
of the heart and arterioles is to secure an adequate flow of
blood through these smallest vessels — that is, a supply of
blood adequate to the needs of the tissues in which the
capillaries are embedded. The transudation of lymph and the
chemical interchange between the tissues and the blood take
place only in the region of the capillaries and small veins.
At present we have no evidence of an influence of the nervous
system on the calibre of the capillaries, or on the interchange
taking place between them and the surrounding tissues,
although the circulation here is indirectly affected by changes
induced in the calibre of the arterioles.

The condition of the endothelial wall of the capillaries and
its influence on the blood-stream seem to be chiefly dependent
on the nutrition of the surrounding tissues. This is well
exemplified in the series of phenomena classed under the head
of inflammation. By inflammation we understand those
processes wherein the organism reacts to a destructive lesion
of its tissues ; and these processes in the higher animals are
connected with marked vascular changes, which can be well
studied on the tongue of the frog. If this be spread out and
arranged for microscopical observation, a beautiful picture of
the normal circulation of the blood through the arterioles,
capillaries, and veins is afforded. As a destructive lesion to
call forth inflammatory changes, a small piece of the tongue
may be cut off, or the tongue may be painted with a very
weak solution of croton oil. The following series of pheno-
mena are then observed. At first the injury is followed by a
dilatation of all the vessels, consequent upon dilatation of the
arterioles ; the blood rushes through the capillaries, and many
vessels make their appearance which were before invisible.
After a time, the vessels still remaining dilated, the stream of
blood becomes slower, and it is then seen that in the small
veins there are two layers : a layer next the vessel wall, in

THE VASCULAR MECHANISM 281

which large numbers of leucocytes are present, and which
remains almost stationary ; and an inner layer of slowly
moving red corpuscles. Since this slowing of the circulation
is unattended by any narrowing of the calibre of the vessels,
it must be due to an increased friction between the blood-
plasma and its contents and the capillary wall. It has been
explained by saying that the layer of endothelium is more
adhesive. In the capillaries the endothelium is also thickly
covered with leucocytes, but here the red corpuscles are
mixed with the leucocytes, and there is not such a division
into two layers as in the veins. Very soon, at one or two
spots, it will be observed that a leucocyte is squeezing itself
or being squeezed through the capillary wall, so that half of
it lies inside, half of it outside the vessels, and the emigra-
tion speedily becomes complete. This emigration of white

Fig. 156.

Emigration of leucocytes through capillary wall. (Arnold.)

blood -corpuscles increases in extent, and at the end of seven
or eight hours the tissues in the immediate neighl;ourhood
of the small veins and capillaries are infiltrated with masses
of leucocytes. At the same time the amount of lymph that
transudes through the vessel-walls is largely increased, so
that it cannot be carried off quickly enough by the lymphatics,
and remains in the interstices of the tissues, causing a swelling
or oedema.

The true significance of this process of inflammation
has been pointed out in recent years by Metchnikoft'. This
observer has shown that all the vascular phenomena of in-
flammation are directed towards furthering the emigration of
leucocytes, and that these leucocytes, or ■pliagocytes, have the
power of devouring the irritant body if it be a micro-organism,
or of removing the tissues killed by the lesion, and so clearing
the ground for a regeneration of the tissue. It is probable

282 PHYSIOLOGY

that the ingestion of micro-organisms is often preceded by
the secretion of some material from, e.g. the eosinophile
cells, which kill the bacteria or prepare them in some way
for their ingestion. Such a condition of phagocytosis —
that is a collection of wandering cells to devour and remove
disintegrated tissues, foreign bodies, or micro-organisms —
has been shown to occur in all animals, even in those
destitute of a vascular system. The animals with such
a system have the advantage over the lower animals,
in that the circulating blood is always bringing up fresh
relays of leucocytes to vanquish and destroy the offending
body. In many cases the chemical or microbic influence
destroying the tissues is too powerful for the leucocytes to
overcome ; they also are destroyed, and the dead leucocytes
collect in the tissues and form pus. If the leucocytes are
successful in removing the irritant body, they disappear,
perhaps wandering back into the blood-stream, and the lost
tissue is replaced by regeneration of the surrounding tissues.

THE VASCULAR MECHANISM 283

Section 9
VARIATIONS IN THE QUANTITY OF BLOOD

From a few observations on executed criminals it has been
determined that the amount of blood in the human body
forms about one-thirteenth of the body-weight. Thus a man
weighing 65 kilos would have about 5 kilos of blood in his
vessels.

The determination of the total hloocl is carried out in tlie following way. A
small sample of blood is taken and diluted one hundred times with distilled
water. The animal is then bled to death, the blood defibrinated, and the
vessels washed out with water, until the outflowing fluid is no longer tinged
with hfgmoglobin. The organs very rich in blood, such as the liver and spleen,
are minced and washed free fi'om h.Tmoglobin. All the blood and the washings
are then mixed together, and diluted with water until the tint of the mixture is
exactly identical with that of the first sample. We then have only to divide
the total volume by 100 to arrive at the amount of blood contained in the animal's
vessels.

A method has been devised by Haldane by means of which the total volume of
blood can be determined in the living subject. The animal or man experimented
on is made to breathe in and out of a bag containing a measured quantity of
CO gas, mixed with pure oxygen. The expired air is allowed to pass through
soda lime on its way back to the bag in order to absorb the carbon dioxide, and
fresh oxygen is supplied from a reservoir as that in the bag is used up. When
the oxygen has displaced all the CO gas into the lungs, the bag is disconnected,
and a sample of blood taken, the relative amounts of CO-htemoglobin and of
oxyhemoglobin being determined by a colorimetric method. The amount of
CO-ht'Emoglobin can be estimated from the amount of CO absorbed in the
course of the experiment ; and since the proportion of CO-hasmoglobin to total
haemoglobin has been also determined, it is easy to calculate the total amount
of hfemoglobin in the body.

A determination of the relative content of the blood in haemoglobin now
enables us to calculate the total mass of blood. Estimations carried out in this
way by Haldane and L. Smith led to the conclusion that the amount of blood
in the body is not J^ as generally assumed, but less, varying in different indi-
viduals from jig to 3L, the average being J^...

PletJiora and HydrcBmic Plethora

The effects of increasing the total volume of circulating
fluid may be studied by injecting several hundred cubic
centimetres of defibrinated blood or normal saline fluid into
a vein. In the latter case, since the blood is rendered more
dilute, the condition is called hydraemic plethora.

On the arterial pressure the result of guch an injection is

284 PHYSIOLOGY

not very marked. There is a slight initial increase in the
pressure, but the increase is by no means proportional to the
amount of fluid injected, showing that the fluid is not to any
large extent contained in the arterial system. On examining
the pressure in the veins however we find a very great relative
rise of pressure, and on opening the abdomen it is seen that all
the veins are distended and that the liver is swollen. The
effect of increasing the volume of circulating fluid would be to
increase the mean systemic pressure, and therefore one would
expect to find a large increase both in arterial and venous
systems. But the organism prevents the rise on the arterial side
by relaxing the whole system of arterioles, so that the distri-
bution of pressures is altered, and the venous approximates
more closely to the arterial pressure. This arterial dilatation
however augments the velocity of the blood : it has been
found that the velocity may be accelerated to six or eight
times the normal rate by injecting an amount of salt solution
equivalent to 50 per cent, of the total blood.

The high venous pressure causes increased diastolic filling
of the heart, and therefore augments both strength and fre-
quency of the beat. Thus the work of the heart is increased
in three ways, viz. by : —

(1) Piise of arterial pressure.

(2) Greater frequency of beat.

(3) Increased output at each beat (Fig. 143).

These series of changes result however in the relief of the
vascular system. The heightened pressure in the abdominal
veins and capillaries causes a great leakage of fluid in the
form of lymph from the capillaries of the intestines and liver,
while the increased pressure and velocity of the blood in the
glomeruli of the kidney induce a copious secretion of urine,
so that within a couple of hours after the injection of salt
solution the volume of the circulating fluid may have returned
to normal.

This recovery is effected with greater difficulty if the
plethora has been brought about by the injection of defibri-
nated blood, since this fluid cannot escape rapidly from
the capillaries, nor can it be excreted unchanged by the
kidneys. Hence it is easy to kill an animal by wearing out
its heart, if too large quantities of defibrinated blood be in-
jected. The ultimate fate of the injected blood is to be]_used

THE VASCULAK MECHANISM 285

as food by the tissues, and to be eliminated by the ordinary
channels.

It must be remembered that the blood serum of one animal is often poisonous
for the corpuscles of another. Thus a few e.c. of dog's serum injected into
the peritoneal cavity of a rabbit will cause death. This poisonous action
is also shown by mixing dog's serum with defibrinated rabbit's blood, in
which case the red corpuscles of the latter are broken up, setting free hemo-
globin (licemohjsis).

The Effects of Hcemorrhage. Ancemia

Any diminution of the total volume of the blood, as by
bleeding, would tend to lower the pressure on both sides of
the system. The vaso-motor centre however strives to main-
tain a normal arterial pressure, and so the circulation through
the brain unaltered. This object is carried out by a general
vascular constriction, which diminishes the total capacity of
the system and alters the distribution of pressure throughout
the system, tending to keep the blood as much as possible
on the arterial side. Thus a slight loss of blood has no
influence on the arterial blood-pressure, but causes a fall of
pressure in the veins, blanching of the abdominal organs, and
diminished flow of urine. The heart beats very frequently,
and so aids in emptying the venous into the arterial system.

The deficiency of circulating fluid caused by bleeding is
soon remedied by a transfer of fluid from the tissues to the
blood. This transfer is independent of the flow of lymph
from the thoracic duct into the blood, and is the direct
consequence of the universal fall of capillary pressure which
results from the bleeding. The abstraction of fluid from the
tissues is responsible for the extreme thirst which is the result
of haemorrhage, and which directs the animal to take up by
the alimentary canal the fluid which is wanting to the body.

This transfer of fluid from tissues to blood is extremely
rapid ; even during the course of a bleeding it is found that
the later samples of blood are more dilute than those obtained
at the beginning.

This mechanism sufiices only to make up the supply of
circulating fluid. After a bleeding however an animal has
lost proteids and blood-corpuscles, and these constituents of
the blood are but slowly restored, the former directly from
the food, the latter by an increased activity of the blood-
forming cells in the red marrow.

286 PHYSIOLOGY

CHAPTER VII
LYMPH AND TISSUE-FLUIDS

In no part of the body does the blood come m actual
contact with the living cells of the tissue. In all parts
the blood flows in capillaries with definite walls consist-
ing of a single layer of cells, and is thus separated from the
tissue-elements by these walls and by a varying thiclmess
of tissue. In some organs, such as the liver and lung, every
cell is in contact with the outer surface of some capillary ;
while in others, such as cartilage (which is quite avascular),
a considerable thickness of tissue may separate any given
cell from the nearest capillary. A middleman is thus needed
between the blood and the tissues, and this middleman is
the lymph which fills spaces between all the tissue-elements,
so that any tissue can be regarded as a sponge soaked with
lymph.

Throughout these spaces we find a close network of
vessels lined, and separated from the tissue spaces, by a
layer of extremely thin endothelial cells, and this plexus com-
municates with definite channels — lymphatics, by which any
excess of fluid in the part is drained off. The lymphatics
all run towards the chest, where those of the limbs join
a large vessel (the receptaculum chyli), which carries the
lymph from the alimentary canal, to form the thoracic duct.
This runs up on the left side of the oesophagus, to open into
the great veins at the junction of the left internal jugular
with the subclavian vein. A small vessel on the right side
drains the lymph from the right upper extremity and right
side of the chest and neck.

The lymph may be looked upon as a part of the plasma
which exudes through the capillary wall, bathes all the
tissue-elements, passes between the endothelial cells into the
peripheral lymphatic network, whence it is carried by lym-

LYMPH AND TISSUE-FLUIDS 287

phatic trunks into the thoracic duct, by which it is returned
again to the blood.

It is easy to obtain lymph for examination by putting
a cannula (a small tube of glass or metal) into the thoracic
duct, and collecting the fluid that drops from it in a glass
vessel.

We may also tap in a similar way one of the large lym-
phatic trunks of the limbs ; but in the latter case we have to
use artificial means to induce a flow of lymph, since little or
none can be obtained in a normal animal from a limb at rest ;
the only part of the body, where there is normally a constant
flow of lymph, being the alimentary canal. And thus we
cannot regard the flow of lymph from a part as any index of
the chemical changes going on at that part. In a limb at
rest foodstuffs are being taken up from the blood and being
burnt up by the muscles with the production of CO,, although
we may not be able to obtain a drop of lymph from a cannula
in one of the lymphatics.

The lymph is thus truly a middleman ; as any substance,
oxygen or foodstuff, is taken up by a tissue-cell from the lymph
surrounding it, this latter recoups itself at once at the expense
of the blood.

Thus there would seem to be no need for lymphatics to
drain the limb, were it not that under many conditions which
we shall study directly, the exudation of lymph from the
blood-vessels is so excessive that, if it were not carried oft" at
once and restored to the blood, it would accumulate in the
tissue-spaces, give rise to dropsy, and by pressure on the cells
and blood-vessels affect them injuriously.

Properties of Lymph

Lymph obtained from the thoracic duct of an animal
varies in composition and appearance according to the con-
dition of the animal, whether recently fed or fasting. From
a fasting animal the lymph is a transparent liquid, generally
slightly yellowish, and sometimes reddish from admixture of
blood-corpuscles. When obtained from an animal shortly
after a meal, it is milky from the presence of minute particles
of fat that have been absorbed from the alimentary canal.
In the latter case, if the intestines be exposed, the small

288 PHYSIOLOGY

lymphatics are to be seen as white lines running from the
intestine to the attached part of the mesentery. It is owing
to this fact that these lymphatics have received the special
name lacteals, the lymph in them being called the chyle.
The fatty particles form the molecular basis of the chyle.

On microscopic examination the transparent lymph of
fasting animals presents colourless corpuscles similar to those
of blood, or perhaps we ought to say identical, since the
leucocytes of the blood are probably derived from the cor-
puscles that have entered with the lymph through the
thoracic duct.

All the lymphatics pass at some point of their course
through lymphatic glands, which we may look upon as fac-
tories of leucocytes, since these are much more numerous
in the lymph after it has traversed the gland than before.
Leucocytes are also formed in all the numerous localities
where we find adenoid tissue, such as the tonsils, air passages,
alimentary canal (Peyer's patches and solitary follicles),
Malpighian bodies of the spleen, and thymus.

The lymph is alkaline, has a sp. gr. of about 1015, and
clots at a variable time after it has left the vessels, forming
a colourless clot of fibrin, just like blood-plasma. It contains
about 6 per cent, of solid matters ; the proteins consisting of
fibrinogen, paraglobulin, and serum albumen. The salts are
similar to those of the liquor sanguinis, and are present in
the same proportions.

The Production of Lymph

Many physiologists have thought that, in the transudation
of the fluid which forms the lymph, there is an active inter-
vention on the part of the endothelial cells composing the
capillary wall, and that lymph is therefore to be regarded as
a true secretion. A careful investigation of the known experi-
mental facts has failed to show that the endothelial cells act
otherwise than passively, as filtering membranes of variable
permeability. The factors which are responsible for the
transudation of lymph may be divided into two classes —
mechanical and chemical, the former depending largely on
the pressure of the blood in the vessels, and the latter chiefly
on the metabolism of the cells outside the vessels.

LYMPH AND TISSUE-FLUIDS '289

According to the views here laid down, the formation of
lymph may be compared to a process of filtration. If this
view is correct, the amomit of lymph formed in any given
capillary area must be dependent on the difi'erence of pres-
sure between the blood in the vessels and the fluid in the
extravascular tissue-spaces. This latter pressure is normally
extremely low, so that in attempting to test the truth of this
view, we must try the effects of altering the pressure inside
the vessels, in the expectation of finding that the Ijanph pro-
duction will rise and fall as the capillary pressure is increased
or diminished. On attempting to carry out such experiments
in different parts of the body, we have to recognise another
factor besides the capillary pressure, viz. the permeability of
the vessel-wall. Whereas the capillary walls in the limbs
and connective tissues generally present a very considerable
resistance to the filtration of lymph through them, and keep
back the larger portion of the proteins of the blood-plasma,
the intestinal capillaries are much more permeable, givmg at
moderate capillary pressures a continual flow of lymph and
separating off only a small proportion of the proteins. It is
in the liver however that we find the greatest permeability.
Here a very small pressure suffices to produce a great transu-
dation of lymph, containing practically the same amount of
protein as the blood-plasma from which it is formed.

The ease with which fluid passes out from the capillaries of the liver is
probably due to the fact that these vessels, unlike most other capillaries of the
body, have not a complete endothelial lining. Thus it is impossible to display
a continuous endothelial lining by means of silver nitrate. The cells surround-
ing the capillaries are large and branched, and possess marked phagocytic
powers, so that after an injection of carmine granules or bacteria into the
blood stream these bodies are found in quantity within the cells. Owing to the
incompleteness of this investment, the liver cells in many places abut on
the lumen of the capillary. On injecting the blood system of the liver, the
injection is found to run with ease into channels situated within the cells
themselves, and it is reasonable to conclude that the blood plasma takes the
same course through these intracellular channels, by which it passes into
the lymphatics which lie at the periphery of the lobules.

In experiments on the lymph production in the limbs
alterations of capillary pressure have but slight effect. The
lymph-flow from a limb lymphatic is practically unaltered by
changes in its arterial supply, although a definite increase
may be obtained by ligaturing all the veins of the limb so as
to cause a very great rise of capillary pressure. The lymph-

19

290 PHYSIOLOGY

flow from the intestines can be measured by collecting the
lymph from the thoracic duct. If the lymphatics which
leave the liver in the portal fissure be previously ligatured,
the whole of the thoracic duct lymph in an animal at rest is
derived from the intestines. It will be found that lowering
of the capillary pressure in these organs by obstructing the
thoracic aorta stops the flow of lymph absolutely, whereas a
rise of capillary pressure, such as that produced by ligature
of the portal vein, causes a four- or five-fold increase of the
lymph.

The effect of rise of capillary pressure on the lymph-flow
is still more striking in the case of the liver. If the inferior
vena cava be obstructed just above the opening of the hepatic
veins, there is a great fall of arterial pressure, but, owing to
the damming back of the blood, a rise of pressure in the liver
capillaries to three or four times the normal amount. This
rise causes an enormous increase in the lymph -flow from the
thoracic duct. The lymph may be increased eight to ten
times in amount, and it contains more protein than before.
If the portal lymphatics be previously ligatured, obstruction
of the inferior cava has no effect on the lymph-flow, showing
that the whole of this increase is derived from the one region
of the body where the capillary pressure is increased, viz. the
liver.

We must conclude that in those regions of the body where
the capillaries are fairly permeable, the most important factor
in the lymph production is the intracapillary pressure.

In the case of the limbs and connective tissues generally,
the pressure factor is probably, under normal conditions, of
less importance, so that the second condition, the chemical,
comes here more into prominence. The capillary wall not
only permits of filtration under certain pressures, but also
allows the passage of water and dissolved substances by diffu-
sion and osmosis. These osmotic interchanges between blood
and cell through the intermediation of the lymph are con-
stantly going on in the normal life of the tissue, and are quite
independent of the amount of lymph produced. Thus a
gland-cell may use up oxygen, calcium, or sugar, and create
a vacuum of these substances in the layer of lymph imme-
diately surrounding the cell. There is at once a disturbance
of the equilibrium, and a flow of these substances from blood

LYMPH AND TISSUE-FLUIDS 291

to lymph is set up. In consequence of the wonderful arrange-
ments m the tissues for ensuring the intimate contact of
blood and lymph without intermingling, these changes can
occur with great rapidity. We find, for instance, that if a
very large amount (40 grms.) of dextrose be injected into the
circulation, osmotic equilibrium between blood and lymph is
established within half a minute of the termination of the
injection. In this case the rise of osmotic pressure ^ caused
l)y the injection of the sugar attracts water from the lymph,
and this in its turn from the tissue-cells, until the osmotic
pressure inside and outside the vessels is the same. By
this means the volume of the circulating blood is increased
at the expense of the tissues. A process of this character

Fic. 157.

^L^mph spaces

'Secreting
cells.

•''^-- Blood

I
I
Duct.

\

Basement
membrane

capillarjf.

Diagram to show relation of the secreting cells of a gland to the
blood and lymph supply.

may however work under normal circumstances in the
reverse direction, and lead to a passage of fluid from blood
to tissues and tissue-spaces. Every active contraction of
a muscle, for instance, is attended by the breaking down
of a few large molecules into a number of smaller ones, and
this increase in the number of molecules causes a rise of
osmotic pressure in the muscle-fibre and surrounding lymph,
and therefore a passage of fluid from blood to lymph. In the
same way a cell of the submaxillary gland, when stimulated
by means of its nerve, pours out a quantity of fluid into the
gland-duct, and so into the mouth. This fluid comes in the

' A fuller description of the phenomena of osmotic pressure will be found in
Chapter X.

21)2 PHYSIOLOGY

first instance from the cell itself, but the cell recoups itself
from the surrounding lymph, raising the concentration of this
fluid, and the difference in concentration thus caused at once
induces a passage of water from blood to lymph (Fig. 157).
Hence salivary secretion is associated with a large flow of
fluid through the capillary walls of the gland. In this passage
the endothelial cells of the capillaries play no part, the whole
process being conditioned by changes in the extravascular
gland-cell. We have only to paralyse the gland -cell by means
of atropin in order to see that the active flushing of the gland
which accompanies activity produces merely a minimal in-
crease in the lymph -flow from the gland.

The influence of tissue-activity in the production of lymph
is still better shown in the case of a large gland, such as the
liver. Stimulation of this organ by the injection of bile salts
into the blood-stream causes a large increase in the lymph-
flow from the organ, and therefore in the lymph-flow from the
thoracic duct.

It is important to remember that the relative insuscep-
tibility of the limb capillaries to pressure holds only for the
absolutely normal capillary. Any factor which leads to im-
paired nutrition of the vascular wall, such as deficiency of
supply of blood or oxygen, the presence of poisons in the blood
or in the surrounding tissues, scalding or freezing, increases
at the same time its permeability. Under such conditions
the limb capillary reacts to changes of pressure like a liver
capillary, the slightest increase of pressure causing an appreci-
able increase in the lymph production. This increased lymph
production may be too great to be carried off by the lymphatic
channels, so that the exuded fluid stays in the tissue-spaces,
distending them and causing the condition known as oedema
or dropsy.

Lymphagogues. — Among the substances which have a
direct action on the vessel wall are a number of bodies which
were described by Heidenhain as lymphagogues of the first
class. As their name implies, these bodies on injection into
the blood-stream cause an increased flow of lymph from the
thoracic duct. They may be extracted from the dried tissues
of crayfish, mussels, or leeches by simple boiling with water.
Commercial peptone has a similar effect. Heidenhain regarded
these bodies as direct excitants of the secretory activities of

LYMPH AND TISSUE-FLUIDS

293

the endothelial cells. They are however general poisons,
having a special action on the vascular system, and their
effect on the lymph production is probably due simply to their

Fig. 158.

1 1

1

\
\
1

—

I
\

\

\

\

1

1

a 1

^

X
X

}

^

=:r-:

X

[-» .^ <

n-

::r

F--

"^^^^

— --

----

---,

0123*5678910

Inj of 40 grams dextros
10

-

■— ^

r"^

1 — -^

'-■■;■' 1

1

^\:

^

\ — ■ —

"""

*

'f^lT*"*'

^^

-.►-

—

^.--

1

0I2J45678910 20 30 40 50 60 minutes

Bled to 240 ccm Inj 13 grams dextrose

Curves to show the influence of intravenous injection of dextrose on
the arterial and venous pressures and on the flow of lymph from
the thoracic duct. The upper diagram represents the effect of
the injection of dextrose in a normal animal, i.e. rise of arterial
and venous pressures, and large increase in lymph. The lower
curve shows the effect of injecting dextrose after a preliminary
bleeding. In this case the fluid attracted into the vessels by the
sugar only just suffices to make up for that lost in the bleeding.
Hence the venous and arterial pressures are little altered from
normal, and there is very little increase in the lymph flow.

In both diagrams —

Thick continuous line = arterial blood-pressure in cm. Hg.
Thin „ ,, = portal ,, in cm. water.

Thin dotted line = vena cava ,, ,, „

Thick „ = lymph-flow in c.e. per ten minutes.

deleterious action on the capillary wall. Although these
bodies act chiefly on the liver capillaries, so that the main
increase in the thoracic duct lymph is derived from the liver,

294 PHYSIOLOGY

they can be shown also to have some effect in the same
direction on the intestinal and skin capillaries. In fact the
injection or ingestion of these bodies often gives rise to a
copious eruption of nettle-rash, i.e. swellings of the skin due
to an increased exudation of lymph into the meshes of the
cutis.

An increased lymph -flow from the thoracic duct may be
produced also by the injection of large amounts (10 to 40
grms.) of innocuous crystalloids such as dextrose, urea, or
sodium chloride into the circulation. In this case the lymph
becomes much more dilute. The explanation of the action of
these bodies is very simple. We have already seen that injec-
tion of large amounts of dextrose into the circulating blood
raises the osmotic pressure of this fluid. The blood there-
fore imbibes water from the tissues and swells up, i.e. a con-
dition of hydraemic plethora is brought about as surely as if
several hundred cubic centimetres of normal salt solution were
injected into the circulation. This increase in the total volume
of the blood causes a rise of pressure throughout the vascular
system, — arteries, capillaries, and veins, — and the increased
capillary pressure combined with the watery condition of the
blood induces a great transudation of lymph, especially in
the abdominal organs. The lymph is more watery because
the blood also is diluted. That the action of these bodies
is purely mechanical is shown by the fact that, if the rise of
capillary pressure be prevented by bleeding the animal imme-
diately before the injection, the increase in the lymph-flow is
also prevented (Fig. 158, p. 293), although the concentration
of the sugar or salt in the blood is still greater than in the
experiments in which bleeding was not performed.

Movement of Lymph

In the frog the circulation of lymph is maintained by
rhythmically contracting muscular sacs, which are placed in
the course of the main lymph-channels, and pump the lymph
into the veins. In the higher animals and in man, the onward
flow of lymph is effected partly by the pressure at which it is
secreted from the capillaries into the interstices of the tissues,
but also to a large extent by the contractions of the skeletal
muscles. In the smaller lymph -radicles the pressure of

LYMPH AND TISSUE-FLUIDS 295

lymph may attain 8 to 10 mm. soda solution. In the thoracic
duct, at the point where it opens into the great veins of the
neck, the pressure is obviously the same as in these veins,
that is to say, from — 4 to 0 mm. Hg, the negative pressure
being occasioned by the aspiration of the thorax. This differ-
ence of pressure is sufficient to cause a certain amount of
flow. It must be remembered however that under normal
circumstances no lymph at all flows from a resting limb.
The only part of the body which gives a continuous stream
of lymph during rest is the alimentary canal, the lymph
in which is poured out into the lacteals, and thence makes its
way through the thoracic duct. Movement, active or passive,

Fij. 159.

A lymi)liatic vessel laid open to show arrangement of the valves.
(Testut.)

of the limbs at once causes a flow of lymph from them.
Since the lymphatics are all provided with valves (Fig. 159),
the effect of external pressure on them is to cause the
lymph to flow in one direction only, i.e. towards the thoracic
duct and great veins. Hence we may look upon muscular
exertion as the greatest factor in the circulation of lymph.
The flow of lymph from the commencement of the thoracic
duct in the abdominal cavity to the main part of it in the
thoracic cavity is materially aided by the respiratory move-
ments ; since, with every inspiration, the lacteals and abdo-
minal part of the duct are subjected to a positive pressure,
and the intrathoracic part of the duct to a negative pressure,
so that lymph is continually being sucked into the latter.

The Absorption of Lymph and Tissue-fluids

On injecting a coloured solution or suspension into the
connective tissues of any part of the body, and gently kneading
the part, it is found that the fluid fills all the lymphatic

296 PHYSIOLOGY

channels running from the part ; and we can in this way
inject the lymphatics of the limb and trace their course on
to the thoracic duct. The same path is taken by micro-
organisms as they spread in the tissues, or by particles of
carmine or Indian ink which have been introduced in tattoo-
ing. It is on account of these facts that the lymphatics are
often spoken of as the absorbent system.

This process of lymphatic absorption is however a slow
one, unless aided to a large extent by passive or active
movements of the surrounding parts, and cannot therefore
account for the rapid symptoms of poisoning which super-
vene within two or three minutes after the hypodermic
injection of a solution of strychnine or other poison. That
this absorption is not dependent on the lymphatics is shown
by the fact that the symptoms occur almost as quickly, when
all the tissues of the limb have been severed with the excep-
tion of the main artery and vein. In the same way, after
injecting methylene blue or indigo carmine into the pleural
cavity or subcutaneous tissues, the dye-stuff appears in the
urine long before any trace of colom* can be perceived in the
lymph flowing from the thoracic duct. The absorption in
these cases is by the blood-vessels, and consists in an inter-
change between blood and extravascular fluids, apparently
dependent entirely upon processes of diffusion between these
two fluids. So long as any difference in composition exists
between the intra- and extra-vascular fluids, so long will
diffusion -currents be set up, tending to equalise this difference.

More difficulty is presented by the question of the
mechanism of absorption by the blood-vessels of the normal
tissue-fluids — such an absorption as we have seen to occur
after loss of blood by haemorrhage. It seems probable
however that this absorption depends on the small proportion
of protein contamed in the tissue-fluid as compared with the
blood-plasma. If blood-serum be placed in a bell-shaped
vessel (the mouth of which is closed by a gelatinous mem-
brane which does not permit the passage of protein), and
suspended in normal salt solution, it is found that the serum
absorbs the salt solution until the manometer attached to the
bell -jar indicates a pressure of 25-30 mm. Hg. Thus we
may conceive that there is normally a balance in the capil-
laries between the processes of exudation and of absorption.

LYMPH AND TISSUE-FLUIDS 297

the former being conditioned by the capillary blood-pressure
and the latter hy the difference in protein content, and there-
fore of osmotic pressure between the blood-plasma and tissue-
lymph. A rise of capillary pressure will upset this balance
in favour of transudation and the blood will become more
concentrated, whereas a fall of pressure will turn the scale in
favour of absorption and the volume of blood will be increased
at the expense of the tissue-fluids.

The Part played by the Lymph in the Nutrition of
THE Tissues

The fact that the tissue-cells are separated by the lymph
and the capillary wall from the blood shows that in all inter-
changes between the blood and tissues, the lymph must act
as the medium of communication. The l^anph-flow however
plays very little part in this process. The muscles of a
resting limb are taking up nourishment as well as oxygen
from the blood and giving off their waste products — carbonic
acid and ammonia, though not a drop of lymph may flow
from a cannula placed in a lymphatic trunk of the limb. In
fact the interchange of material between tissue-cell and blood
through the mediation of the lymph is carried out m the
same way as are the gaseous interchanges, viz. by a process
of diffusion. This explanation however holds good only for
the diffusible constituents of the blood and will not account
for the supply of the indiftusible protein molecules to the cell.
Apparently the only way in which the tissues can obtam their
supply of protein is from the small proportion of this substance
which has filtered through the vessel-wall into the lymph.
The increased exudation of concentrated lymph to the tissues
which occurs in inflammatory conditions or as the result of
injuiy is therefore of advantage, since it furnishes an abun-
dant suppl}' of protein food to be used up in the regeneration
of the damaged cells.

298 PHYSIOLOGY

CHAPTER VIII
THE MECHANISMS OF DIGESTION

Section 1

GENEEAL CHARACTEES OF THE PROCESSES OF
DIGESTION

We have already mentioned that the cells derived from
the hypoblast of the embryo, and lining the inner surface of
the tube from which the body is formed, are alimentary in
function, i.e. they have the office of taking up the various
foodstuffs and converting them into a form suitable for
assimilation by the other tissues of the body. In some of the
lower animals the cells lining the alimentary canal devour
the food particles in the same manner that the amoeba does,
secreting around them, after ingestion, a fluid which seems
to dissolve them. In the higher Vertebrates this process is
simplified, in that the cells lining the canal are differentiated
into those that secrete a fluid capable of dissolving foodstuffs,
and those which have the duty of absorbing the foodstuffs
that have been rendered soluble by the action of the digestive
fluids. The secreting cells are collected together in depressions
or outgrowths of the epithelial lining of the alimentary canal
to form glands ; and the secretions in different parts of the
canal have different properties, some being adapted to rendering
soluble the starchy constituents of food, while the action of
others is limited to proteins.

During the time that the food is in the mouth it is acted
upon by the mixed secretions of the parotid, submaxillary,
and sublingual salivary glands. And here we find the chief
digestive action consists in the conversion of insoluble starch
into soluble dextrins and sugar.

In the stomach the food is acted on by the gastric juice,
the secretion of a number of simple tubular glands with

THE MECHANISMS OF DIGESTION 299

which the mucous membrane is thickly set. Its chief action
is on the proteins, hydrating these and converting them into
albumoses and peptones. In the duodenum the food is acted
on by the pancreatic juice and the bile, the secretion of the
liver. The former has a digestive influence on all three
classes of foodstuffs, converting starch into sugar, proteins
into peptones, and splitting up neutral fats with the forma-
tion of glycerin and free fatty acids. In the small and
large intestine the mucous membrane is thickly set with a
number of simple tubular glands, which are called Lieber-
kiihn's follicles. These secrete an alkaline juice, which has
only slight digestive powers. It contains invert ferments
which convert cane-sugar into laevulose and dextrose, and
maltose into dextrose, and also a ferment, crepsin, which has
the proj)erty of causing a complete hydrolysis of the albumoses
and peptones already formed by the agency of gastric and pan-
creatic juices, and converting them into amino-acids and bases.

Ferments. — All the digestive juices owe their powers to
the presence in them of certain ferments ; and we ma}^ take
the opportunity of saying a few words with regard to ferment
action in general. Ferments enter or are said to enter into
most of the physiological processes of the body. To a fer-
ment has been ascribed a prominent part in the coagulation
of the blood ; and we shall meet with them later on in con-
sidering the functions of the liver and kidney. But it is in
digestion that these bodies play the most important part. In
all the changes that are effected by their agency there is the
conversion of a body of high potential energy into one with
less potential energy ; and this conversion is in most cases
associated with hydrolysis, i.e. the original body is combined
with one or more molecules of water to form the new substance
of lower potential energy.

In inquiring into the nature of ferments we are met at the
outset with the difficulty that probably no one has ever pre-
pared a pure ferment ; so that we can only study their pro-
perties by studying those of the fluids or precipitates presumed
to contain a ferment from the fact that they can give rise to
certain changes in other substances. First, as to the condi-
tions of their activity. A ferment such as diastase can convert
an indefinite amount of starch into sugar, provided that
the product of its activity {i.e. the sugar) be not allowed to

300 PHYSIOLOGY

accumulate in too large a quantity. Thus l)y increasing the
strength of a ferment solution we do not increase the amount
of substance it is able to transform, but merely the rapidity
of its action.

The exact effect of increasing the amount of ferment varies according to the
nature of the ferment in question. Thus in some cases, as with diastase, the
rapidity of change of the starch is in direct proportion to the amount of fer-
ment present. If a given solution takes four minutes to convert a starch solu-
tion to the ' achromic ' point {i.e. the stage at which no coloration is given with
iodine), a feniient solution of double the strength will take only two minutes to
effect the same change. In the case of other ferments, such as pepsin and
trypsin, it is necessary to increase the concentration of the ferment four times
in order to double the rate of change produced.

A ferment is active only within certain limits of tempera-
ture ; and for each ferment there is a certain optimum
temperature at which its activity is greatest. This, for the
ferments met with in the bod}'-, is between 40° and 45° C.
For the diastase of malt it is between 60° and 65° C. At a
temperature of 0° the activity of all ferments that occur in
warm-blooded animals is indefinitely checked, although it has
been shown that the pepsin or gastric ferment of fishes still
preserves some power at this temperature. At 65° C. all fer-
ments met with in the body are destroyed, and do not recover
on cooling.

They are soluble in distilled water, and precipitated from
their solutions by alcohol. The digestive ferments are pre-
cipitated by saturation of their solutions with ammonium
sulphate. This method has been used for obtaining them in
a state approaching purity, and they have been found to have
the general composition of proteins. The amount that can
be collected however is so small that it is impossible to make
an accurate study of their properties, and even then we do
not know whether the substance we have represents the pure
ferment, or is merely a protein to which the ferment is inti-
mately adherent.

A ferment is therefore a body which can effect changes in
a surrounding fluid of certain bodies of high potential energy
into bodies of more stable composition with an evolution of
kinetic energy in the form of heat, without itself being used
up in the process.

It has long been known that the action of a ferment
was impeded and finally checked by the accumulation of the

THE MECHANISMS OF DIGESTION 301

products of its activity in the solution. Thus diastase added
to a strong solution of starch will convert a certain amount of
it into maltose, but the process will cease before the whole of
the starch is so converted. If now the solution be diluted, or
the maltose removed by dialysis, the action will recommence.
In this respect the reaction exactly resembles those known in
chemistry as reversible reactions.

The question arises whether a ferment action can also be
reversible. An answer to this question has been supplied by
Croft Hill in the affirmative. The inverting ferment, maltase,
contained in yeast and in the succus entericus, converts
maltose into dextrose. If however the ferment be allowed to
act on strong solutions of dextrose, it converts a small pro-
portion of this back into maltose. The changes in the two
cases are as follows :

C,2H,20,, + H.,0 = 2C,H,,0,-
2C,3H,,0,3 =: C,;H,,0„ + H,0

This observation is of importance as showing that synthetic
changes can occur in the body apart from any activity of
cells, provided only that the right conditions are present.
It is evident that, if the sugar were contained in a vessel
whose walls were permeable to or had a distinct affinity for
maltose, so that this was removed as fast as it was formed,
the ferment that normally converts maltose into dextrose
(a downward change) might convert the whole of the dextrose
into maltose.

The changes brought about by ferments can in most
cases be also effected by ver}^ simple means, such as heating
with water under pressure or warming with dilute acids.
The changes are in nearly all cases hydrolytic, the original
substance taking up water, and splitting into simple sub-
stances. In this process the ferment adds neither to the
products of the reaction nor to the energy evolved in the
reaction. The only factor altered by the ferment is the
velocity of the reaction. Cane-sugar in the presence of water
is slowly inverted into Ifevulose and dextrose. If a little
mineral acid be present, or some invertin be added, the
reaction takes place within a few minutes.

The nature of ferment action may be better conceived
if we compare it with certain changes that have long been

302 PHYSIOLOGY

known in inorganic chemistry, and are spoken of as katalytic
changes. Thus nitrogen trichloride may be made to explode
by contact with various substances, such as phosphorus or
oil. In its explosion it splits up into free nitrogen and
chlorine— molecules which are more stable, and have there-
fore less potential energy, than those of the original nitrogen
trichloride. In the manufacture of sulphuric acid, nitric
oxide is used as a carrier of oxygen from the atmosphere to
the sulphur dioxide produced by the burning of sulphur.
Thus :

NO + 0 = NO,.

Nitric oxide Nitrogen tetroxide

SO, + NO.3 -!- H,0 = H2SO, + NO.

Sulphur dioxide Sulphuric acid Nitric oxide

In this case we have at the end of the reaction the same
amount of nitric oxide that we started with ; and it would
be theoretically possible, by using a small quantity of nitric
oxide as oxygen-carrier, to convert an indefinite amount of
sulphur dioxide into sulphuric acid. Since in this reaction
we know the exact chemical processes that go on, the w^ord
' katalysis ' is not used. On the other hand, we employ this
word in speaking of the splitting up of hydrogen peroxide by
means of spongy platinum into water and oxygen :

2H2O. = 2H,0 + 0,.

Hydrogen peroxide

But the difference is probably merely one of degree. The
substance which acts katalytically exercises an attraction on
one of the atoms in the unstable molecule, which is sufficient
to give the impetus to its decomposition, although not leading
to an actual combination of the two, as in the case of the
nitric oxide quoted above. So we may suppose that the
invert ferment, for instance, combines with a molecule of
water, and passes it on to the cane-sugar ; or it may be that
it merely exercises an attraction on some of the constituents
of the cane-sugar molecule, so increasing its tendency to
break up and unite with the surrounding molecules of water,
with the evolution of heat and the production of the more
stable bodies, laevulose and dextrose.

THE ]\IECHANISMS OF DIGESTION 303

Tho ferments which play so important a part in the
digestive functions belong to the class of unorganised fer-
ments. The term ' ferment ' has been applied to another class
of bodies, which are distinguished as the organised ferments.
These are living organisms which have the power of inducing
definite changes in the media in which they live. This
faculty is intimately bound up with the life of these organisms.
Destruction of this by the action of small amounts of
chloroform, or by subjecting them for some time to the action
of absolute alcohol, irrevocably destroys their fermentative
properties. With the organised as with the unorganised
ferments there is a change of the affected substance from
a condition of high to one of lower potential energy. The
changes induced however are often much more than a mere
hydrolysis. The yeast fungus, for instance, converts sugar
into alcohol. In this process it has been thought that the
change represents the metabolism of the organism itself.
But it is becoming more and more difficult to draw a
hard and fast line between the two kinds of action. The
ammoniacal fermentation of urine depends on the presence
of a micro-organism, the Micrococcus urecc, which converts
urea into ammonium carbonate.

/NHj /ONH,

COv + 2H.,0 = C0(

^NH., ' \ONH,

Urea Ammonium carbonate

This action is stopped by antiseptics. It is possible how-
ever to kill the micro-organisms and extract from the dead
cells an unorganised ferment which has exactly the same
effect. In the same way it has been shown that, if yeast
cells be thoroughly broken up and pressed, an unorganised
juice is obtained which converts dextrose into alcohol. In
fact the organised ferments seem to act by ferments enclosed
within their constituent cells, whereas the unorganised fer-
ments are formed by living cells and excreted so as to act
outside the cell.

Eecent research tends more and more to enhance the
significance of these ferment-like bodies, which acting in
infinitesimal quantities are able to exert so important an
influence on the direction and velocity of chemical reactions.

304 PHYSIOLOGY

In the alimentary canal the following ferments are
found : —

Ptyalin (saliva) ; amylopsin (pancreatic juice). Starch to
maltose.

Invertin. Cane-sugar to invert sugar (dextrose and
laevulose).

Lactase. Lactose to dextrose and galactose.

Maltase. Maltose to dextrose.

Pepsin. Proteins to albumoses and peptones.

Trypsin. Proteins to peptones, amino-acids, etc.

Erepsin. Albumoses and peptones to amino-acids and
hexone bases.

Steapsin. Neutral fats to fatty acids and glycerin.

Bennin. Caseinogen to casein.

A whole array of bodies of this class are moreover found
in the cells and body-fluids under normal and pathological
conditions, e.g. toxins and antitoxins, coagulins and haemo-
lysins with their ' anti ' bodies, oxydases, etc. ; and it seems
not improbable that all chemical processes of cells may in
time be reduced to ferment actions, the functions of the living
protoplasm being confined to the determination of the direc-
tion of the process at any moment.

THE MECHANISMS OF DIGESTION

805

Section 2
SALIVAEY DIGESTION

The saliva is a mixture of the secretions of the sub-
maxillary, sublingual, parotid, and small mucous and serous
glands of the buccal cavity (Fig. 160). It has a low specific
gravity, 1002 to 1009 ; it is slightly alkaline, and slimy from
the presence of mucin. On microscopic examination it is seen
to contain epithelial scales and * salivary corpuscles ' — small

Fig. 160.

Dissection to display the salivary glands, a, sublingual gland ;
b, submaxillary gland ; c, parotid gland ; d, common opening
of ducts of submaxillary and sublingual glands ; i, opening of
duct of parotid gland.

round cells with granular contents, which are probably
leucocytes escaped from the tonsils. It consists of —

Water.

Salts, especially potassium and sodium chlorides.

Traces of albumen.

Mucin.

A diastatic ferment (ptyalin).

Occasional traces of potassium sulphocyanide.

Gases, especially carbon dioxide, with traces of oxygen and
nitrogen.

The amount of saliva secreted in twenty-four hours varies
from one-half to two litres. The greater part is re-absorbed
in the alimentary canal.

20

306 PHYSIOLOGY

Action of the Saliva on the Food

Saliva chiefly serves to moisten foodstuffs, and so aid in
mastication and deglutition. This is indeed in carnivora its
sole function. In herbivora and man it exercises a digestive
action on starch by virtue of the ptyalin it contains. If some
saliva be added to some boiled starch in a test-tube, and
the mixture be kept at 35° C. for some time, the starch is
gradually converted into a mixture of maltose and dextrin.
The first stages of this conversion are extremely rapid, as is
shown by the fact that if a warm decoction of starch be taken
into the mouth, kept there for 15 to 30 seconds, and then
ejected, the coloration with iodine has entirely disappeared,
all the starch having in this short time been converted
into dextrin and maltose. The stages of the process are as
follows :

1. Starch, opalescent solution, blue with iodine.

2. Soluble starch, clear solution, blue with iodine.

3. A mixture of dextrins, erythro- and achroodextrin.
The former with iodine gives a mahogany-red colour.

4. Maltose and achroodextrin, the erythrodextrin being
converted into maltose, while some of the achroodextrin re-
mains unaffected. The liquid now reduces Fehling's solution
by means of the maltose it contains, and gives no coloration
with iodine. Addition of large excess of absolute alcohol
gives a white precipitate of achroodextrin. This ferment
action is dependent on temperature, is most active at about
40° C, and is finally abolished at about 60° C. It can only
take place in a neutral or slightly alkaline medium, the
ferment being destroyed in the presence of acid.

It may seem strange that the hydrolysis of starch with the formula CuHuOj
should result in the formation of dextrin with the same formula. It must be
remembered however that these formulae are the simplest possible, and that
the colloidal starch molecule is probably at least one hundred times as large as
the molecule represented by CJi^^Oy The hydrolysis of the starch takes place
by stages resulting in the production of a number of dextrins intermediate
between starch and maltose. The formation of maltose begins at the very
onset of the hydrolysis, so that we may conceive the soluble starch molecule as
made up of a number of groups 3(CsH|o05). Each of these groups would take
up one molecule of water with the formation of maltose and a dextrin.

3(C,H,A) + H,0 = C,H,A + C,,H,,0„.

Dextrin Maltose

THE :\IECHANISMS OF DIGESTION

307

The dextrins themselves however are in most cases more complex bodies than
is here represented, belonging, like the parent molecule, to the class of bodies
known as colloids.

The Mechanism of Salivary Secretion

The digestive juices are formed by the agency of glands.
These are recesses or branching tubules lined with a con-
tinuation of the general alimentary epithelium. This secre-
tory epithelium is separated by a basement membrane from
the surrounding connective tissue, in which ramify blood-
vessels, lymphatics, and nerves. The secretory cells are
bathed by the lymph that exudes from the capillaries ; and
from this lymph they select the substances necessary for
their nourishment, and form therefrom the special ingredients

Fici. 161.

A, serous gland ; B, pure mucous gland from mouth. (Kolliker.)
«, ducts ; /, fat cells.

of their secretion, which they turn out into the lumen of
the gland tubule. This process is an act of vital selection
by the cell, and is not a mere filtration or transudation
of certain constituents of lymph through the epithelial
membrane.

The salivary glands are divided into three classes, the
mucous glands, the serous glands, and glands which partake
of the characters of both these groups. Chief among the
last class are the demilune glands, which are often spoken of
as mucous.

Pure mucous glands are found scattered over the tongue
and mucous membrane of the mouth (Fig. 161, b). They
have large acini which are lined with large clear cells, dis-
tended with mucin. These acini open into a short duct lined
with striated cubical epithelium. Their secretion is thick

308 PHYSIOLOGY

and viscid and consists chiefly of a solution of mucin. The
serous glands occur as small follicles scattered over the
lining of the oral cavity. They have small tubular acini
which are lined with polyhedral granular cells (Fig. 161, a).
Their secretion is watery and consists chiefly of water, salts,
and ptyalin with a trace of albumen and globulin.

Of the three large salivary glands in man, the parotid,
submaxillary, and lingual, the parotid represents a pure
serous gland. The other two belong to the class of demilune
glands : in the submaxillary of man however, lobules of this
nature are mixed with pure serous acini.

The demilune type conforms to the purely mucous gland
in that its acini are large and are lined (in hardened speci-
mens) by a complete layer of large clear swollen cells, which
yield a mucous secretion. Between these cells and the base-
ment membrane however is another type of cells which stain
deeply with haematoxylin, are granular, and are denoted from
their shape crescentic or demilune cells. These cells were
formerly supposed to take the place of the mucous cells
destroyed in the process of secretion, but they have their own
system of ducts, and there seems little doubt that they are
serous cells taking an active part in the secretory process.

All these glands pour their secretions into the mouth, the
active secretion being excited by the presence of food in the
mouth, and by the movements of mastication.

Changes accompanying Activity

The salivary glands may be made to secrete by adminis-
tration of pilocarpin or by stimulation of their nerves. On
histological examination it is found that activity is associated
with marked changes in appearance of the cells. If we
examine a section of a mucous gland that has been in a
resting condition for some time (' resting gland '), the acini
are seen to be distended with large cells having clear hyaline
contents, so close together that no lumen can be seen (Fig.
162). The nuclei situated at the outer border of the cells,
near the basement membrane, appear shrivelled, with irregu-
lar margins.

In a section made through a discharged gland {i.e. one
that has been actively secreting for some time), the acini and

THE MECHANISMS OF DIGESTION

B09

the cells are smaller, the lumen quite distinct, and the nuclei
round and swollen (Fig. 163). The whole section appears
darker from the fact that the cells have taken up the stain-
ing fluid more readily. The difference between the sections
depends chiefly on the fact that, in the sections of the resting
gland, the cells are distended with mucin, which does not take
up the staining agent and gives the cells their clear hyaline

Fig. 162.

Submaxillary gland of dog, after prolonged rest (Eanvier). I, lumen
of alveolus ; g, mucous cells ; c, demilune cells.

Same gland attei piolonyd activity.

appearance. When secretion occurs, the mucin is discharged
into the lumen, so that the cells shrink and consist more
largely of protoplasm.

If, instead of examining sections of hardened glands, we
examme fresh glands teased in normal saline fluid, or fixed
with osmic acid vapour, the appearance presented is quite

310

PHYSIOLOGY

different. The cells of the restmg gland are not clear and
hyalme, but are full of coarse granules. When secretion
occurs these granules disappear. If to a fresh specimen of
resting gland any of the ordinary hardening agents (such as
spirit or Muller's fluid) be added, the granules are seen to
swell up and fuse together to form a hyaline mass distend-
ing the cell. In fact the ordmary picture of the hardened
resting gland is reproduced (Fig. 164).

We see then that the resting gland in a normal condition
does not contain mucin, but contains a precursor of mucin —
mucigen, which appears in the form of granules. As these are
turned out of the cell they undergo some change, perhaps

Fig. 164.

Mucous cells from a fresh submaxillary gland of a dog (Langley).
a. Mucous cell examined fresh from a resting gland, a'. The
same cell treated with weak alcohol, b and b'. Cells from a
discharged gland before and after treatment with weak alcohol.

associated with imbibition of water, and are transformed into
mucin.

A similar change occurs in the serous glands when secre-
tion takes place. The cells of the resting parotid gland,
examined in normal saline fluid, are swollen and full of fine
granules. With activity these granules are discharged, and
the cells shrink and become clearer (Fig. 165).

In the pancreas of the rabbit, which is very similar in
structure to a serous salivary gland, the changes coincident
with secretion can be observed in the living animal, since
here the gland is spread out between the layers of the mesen-
tery, so that individual acini may be examined under high

THE MECHANISMS OF DIGESTION

311

powers. When the resting gland is observed in this way,
each acinus is seen to be composed of two zones, an outer
clear zone and an inner granular zone. The outlines of the
cells cannot be distinguished (Fig. 166). When secretion is
excited by the injection of pilocarpin or other means, the

Fig. 165.

Acini of a serous salivary gland. A. Besting condition.
B. Discharged condition. (Langley.)

inner zone clears up, the granules being discharged into the
lumen ; the homogeneous outer zone becomes wider, while
the nuclei and borders of the individual cells can be clearly
made out.

The amount of ferment to be extracted from the pancreas
seems to be directly proportional to the number of granules

Fi.i. 106.

A terminal lobule of the pancreas of the rabbit. A. In resting condition.
B. After active secretion. (Kiihne and Sheridan Lea.)

present in the cells. But we have evidence, best marked
perhaps in the case of the gastric glands, that these granules
do not themselves represent the ferment but are merely
precursors of the ferment, just as the mucigen granules
in the submaxillary gland are precursors of mucin. These
precursors of ferments are spoken of as zymogens.

312 PHYSIOLOGY

Two changes occur in the cell when secretion takes place.

1. A transformation of zymogen granules into ferment, of
mucigen into mucin, which substances are then discharged
from the cell into the lumen of the gland.

2. A building up or reintegration of protoplasm, as evi-
denced by the growth in extent of the stainable protoplasmic
parts of the cell.

During rest a twofold process is probably going on.

1. A further building up (anabolism) of the protoplasm
of the cell out of the constituents of the surrounding lymph.

2. A katabolism or breaking-down of the cell-protoplasm,
with the formation of zymogen granules, which are stored up
in the cell till the economy requires that they should be con-
verted into ferment and discharged into the lumen.

Active secretion is associated in the living body with —

1. Increased blood-supply. If secretion be excited in the
submaxillary gland by stimulation of the chorda tympani
nerve, a cannula having been previously inserted into the
distal end of a vein coming from the gland, the amount of
blood flowing from the vein is increased eight or ten times.
Before excitation the blood drops slowly from the cannula ;
during excitation it runs freely, has a bright arterial red
colour, and the stream may present pulsations, transmitted
from the arteries through the capillaries.

2. Increased production of CO.,,. The venous blood how-
ever appears bright red, since this increased production is
more than compensated by the increased flow of blood through
the gland.

3. Electrical changes.

If the outer surface and hilus of the submaxillary gland be led off to a
galvanometer, it is found that there is a slight resting current passing in the
dog's gland from hilus to outer surface. "When secretion is excited, this current
undergoes modification in a positive or negative direction, and it seems that the
two events of secretion — cell change and passage of fluid through the gland —
may give rise to opposite results. Thus stimulation of the chorda tympani nerve
gives a positive followed by a negative variation ; stimulation of the sympathetic
gives a pure negative effect. The outgoing current therefore seems to be asso-
ciated with the passage of fluid through the gland-cells.

It might be thought that the secretion was a result of the
larger flow of blood through the gland, and indeed of the
raised pressure in the capillaries, consequent upon the dila-
tation of the arterioles causing an increased transudation.

THE MECHANISMS OF DIGESTION 313

The following facts however show that secretion is an active
process of the epithelial cells, and is not dependent on filtra-
tion.

1. If manometers be inserted in the carotid artery and
in the duct of the submaxillary gland, the pressure of the
secretion may be double as high as the blood-pressure in the
carotid, so that fluid is flowing from the blood-vessels at a
low pressure into the duct at a high pressure — a process not
explicable by any theory of filtration.

2. If atropin be administered, stimulation of the chorda
tympani nerve produces no secretion in the submaxillary
gland, although dilatation of the blood-vessels takes place as
usual.

3. Some secretion may be caused by stimulating the
chorda tympani nerve in a head recently severed from the
hodj.

4. If the submaxillary gland be enclosed in a plethys-
mograph, stimulation of the chorda tympani nerve causes
a shrinkage of the gland, in spite of the concomitant vascular
dilatation, showing that the fluid secreted is supplied
immediately by the cells, and that these only recoup them-
selves later from the lymph and blood. A primary increased
transudation from the blood-vessels would of course be
accompanied by an increase in volume of the gland.

Nerve-supply

The salivary glands have a double nerve-supply, from the
sympathetic and from the cranial nerves. The submaxillary
gland receives its sympathetic fibres from branches of the
cervical sympathetic which ramify on the facial artery, and
its cranial fibres from the chorda tympani nerve. These fibres
run for a short time with the lingual nerve, and then leave
it as a slender nerve which, reaching Wharton's duct (duct
of submaxillary gland), runs along this to the gland. The
fibres are connected in the hilus of the gland with nerve-cells.
A small collection of nerve-cells — the ' submaxillary ' ganglion
— is found m the triangle between the chorda tympani nerve,
lingual nerve, and duct. With the cells of this ganglion are
connected fibres of the chorda tympani going to supply the
sublingual gland (Langley).

314

PHYSIOLOGY

Different effects are obtained according as the chorda
tympani or the sympathetic fibres are stimulated. Stimula-
tion of the chorda tympani in the dog gives rise to an active
dilatation of the vessels of the gland, and a copious watery
secretion containing only a small amount of mucin and
formed elements.

Stimulation of the sympathetic causes constriction of the
vessels, and a scanty flow of very thick viscid saliva, rich in

Fig. 107.

Diagram of nerve-supply to submaxillary gland. Sm.G. Sub-
maxillary gland. N.L. Lingual nerve. Ch.T. Chorda tympani.
Sm.Gl. Submaxillary ganglion. Sm.D. Wharton's duet. V.J.
Jugular vein. C.A. Carotid artery. G.C.S. Superior cervical
ganglion. N.S. Sympathetic fibres ramifying on facial artery.
(After Foster.)

mucin and formed elements. The changes that occur in the
cells are much more marked under sympathetic than under
chorda stimulation. In consequence of the differences in
the action of these two sets of nerve-fibres, they have been
supposed to have two distinct functions. The chorda fibres
are vaso-dilator and secreto-motor of water ; the sympathetic
fibres are vaso-constrictor and secreto-motor of organic
matter. The latter have been also denoted trophic, because
of the marked change in the cells that is caused by their
stimulation. They might well be called the katabolic fibres
of the gland.

There is no doubt that the difference in the action of the two sets of nerves
is in some degree dependent on the variations in the blood-supply produced at
the same time, and that the chorda saliva is more watery because the gland-
cells have more fluid at their disposal.

According to Langley the actions of the gland-fibres of the sympathetic and

THE MECHANISMS OF DIGESTION 31.5

chorda tympani nerves are probably identical, the differences in the saliva
obtained by stimulation of the two sets of nerves being conditioned by the
concomitant vascular changes. Against this view may be urged the fact that
while atropin paralyses the secretory fibres of the chorda tympani, it has
practically no effect on those derived from the sympathetic.

The parotid gland has also a double nerve-supply: fibres
from the cervical sympathetic, and cerebro-spinal fibres run-
ning in the auriculo-temporal branch of the fifth nerve, but
originating probably from the glosso-pharyngeal and running
through the tympanic branch of this nerve (nerve of Jacobson).
Stimulation of the cerebro-spinal fibres produces in the rabbit
and dog a copious flow of limpid saliva of low specific gravity.
Stimulation of the sympathetic causes in the rabbit a scanty
flow of saliva free from mucin, but containing more proteins
and ferment than the cerebro-spinal secretion. In the dog
stimulation of the sympathetic causes no secretion, although
the changes, that we have already described as accompanying
activity, take place in the cells.

Reflex secretion. — The secretion of saliva is normally
brought about reflexly by stimulation of the branches of the
fifth and glosso-pharyngeal nerves distributed to the mucous
membrane of the mouth and tongue, the stimulus being
furnished by the presence of food in the mouth, by acids, or
by the masticatory movements.

The centre for the secretion of saliva is located in the
medulla, since from this part of the central nervous system
arise both the aft'erent and efferent nerves by which the
secretion is regulated. The peripheral nerve-cells, such as
the collection that goes by the name of the submaxillary
ganglion, cannot act as reflex centres, and probably their sole
function is to preside over the nutrition of the nerve -fibres
distributed to the glands.

Paralytic secretion. — If the chorda tympani nerve be cut on one side, the
submaxillary gland enters into a condition of what we might term ' overflow
activity.' If a cannula be placed in Wharton's duct, a constant slight dribbling
of saliva occurs (about 1 drop in 20 minutes). This is known as 'paralytic
secretion,' Sections of the gland present the typical appearance of a resting
gland. This condition is attended by a gradual atrophy of the gland, which
may lose half its weight in a few weeks. Section of the sympathetic does not
give rise to any analogous phenomenon, nor does it stop the paralytic secretion
caused by section of the chorda.

316 PHYSIOLOGY

Section 3
DIGESTION IN THE STOMACH

The food after thorough mastication and admixture with
the saliva passes down the oesophagus into the stomach.
Here sahvary digestion continues until the reaction of the
food is rendered acid by the secretion of gastric juice, a
change which does not occur for twenty to thirty minutes or
even longer. Thus the greater part of salivary digestion
takes place in the stomach.

The stomach is a saccular dilatation of the alimentary
canal, lying obliquely in the abdomen, with the oesophagus
opening into its larger cardiac end or fundus, while its oppo-
site right extremity gradually narrows to the pyloric orifice
which opens into the duodenum. The wall is composed of
four coats, the serous, muscular, submucous, and mucous
coats. The mucous membrane in the contracted condition is
thrown into folds, the submucous coat, which carries the large
vessels and nerves, being very loose in texture. The mucous
membrane consists of a delicate connective tissue rich in
lymphoid elements, covered by a continuous layer of hyaline
columnar cells, and presenting a number of minute pits which
are the orifices of tubular glands set closely together so as to
make up the greater mass of the mucous membrane. The
gastric juice is formed by the activity of these glands.

Two varieties of glands may be distinguished. At the
cardiac end of the stomach the glands are simple tubules,
with short necks or ducts. The secreting part of the tubule
is lined with a single layer of small granular cubical cells
(chief cells) ; between these and the basement membrane are
a number of larger oval cells — parietal or oxyntic cells — which
stain differently from the central cells.

In the pyloric region the glands consist of tubules which
are branched at the end, and have a comparatively long neck
or duct. In this region we find only chief cells, no oxyntic
cells being present. The necks of all the glands are lined
with columnar epithelium, similar to that covering the free
surface of the mucous membrane.

THE MECHANISJMS OF DIGESTION

317

The best method of obtaining pure gastric juice is that
devised by Pawlow, in which the secretion is evoked by letting
a dog eat meat after making openings in the oesophagus and
stomach, so that the food eaten cannot enter the stomach.
Or a diverticulum of the stomach may be established by

Ficx. 169.

Fig. ir.8.

Fig, 168. — A gland from the cardiac end of the stomach (after
Klein), d, duct of the gland ; 6, base of one of its tubules ;
c, central cell ; p. parietal or oxyntic cell.

Fig. 169. — A pyloric gland (Ebstein). m, mouth ; n, neck ;
tr, deep portion of one of the tubules cut transversely.

making an incision as shown in Fig. 170, a, and then reflect-
ing and suturing the mucous membrane, so that a little sac
of the cardiac end is produced in nervous, vascular, and mus-
cular continuity with the rest of the stomach, and separated
from the latter only by a diaphragm consisting of a double
layer of mucous membrane (Fig. 170, b). A secretion of

318

PHYSIOLOGY

gastric juice may then be evoked at any time by allowing the
animal to eat in the ordinary way. Thus obtained it is a
clear, colourless, acid liquid, with a specific gravity varying
from 1001 to 1010. Its chief constituents are two ferments,
pepsin and rennet ferment ; and free hydrochloric acid. The
amount of free HCl in the gastric juice varies from 0" 2-0*3
per cent, in man to 0*6 per cent, in the dog and cat. It also
contains salts, and a large amount of water which constitutes
about 98 per cent, of its bulk.

The hydrochloric acid is shown to exist in a free condition

Fig. 170.

Diagram to show Pawlow's method of making a cul-de-sac of the
cardiac end of the stomach, with vascular and nerve supply intact.
In A the line of the incision into the stomach wall is shown.
B represents the operation as completed. In A : O, a?sophagus ;
B.V., L.V., right and left vagus nerves; P, pylorus; C, cardiac
portion of stomach; A, B, line of incision. In B: V, main portion
of stomach ; S, cardiac cul-de-sac ; A, abdominal wall ; e, e, mucous
membrane reflected to form diaphragm between the two cavities.

from the fact that on elementary analysis the amount of
chlorine present is more than sufficient to saturate the
bases.

It is often of importance to be able to determine the presence of free mineral
acid (HCl) in the gastric contents. Mere acidity to litmus may be due to lactic
or fatty acids produced by fermentation of the contents. The following reactions
may be used to test this point :

a. Paper stained with congo-red turns blue in the presence of free inorganic
or organic acids, but is not altered by acid salts.

b. To some of the stomach-contents an equal quantity of Gunzberg's
reagent (a solution of phloroglucin and vanillin in alcohol) is added and the
mixture evaporated on a water-bath. A delicate rose tint shows the presence of
hydi'ochloric acid.

THE MECHANISMS OF DIGESTION 319

c. A drop of saturated solution of tropaeolin 00 is allowed to evaporate on
a porcelain slab at 40° C, and while at this temperature a drop of the liquid
to be tested is added. On evaporation a violet stain is left if free HCl be
present.

An artificial gastric juice may be prepared by digesting
the fresh mucous membrane of the stomach with 0*2 per cent.
HCl at 40° C. for some hours and then filtering from the
undissolved nucleins of the cells. The fluid thus obtained
contains a large proportion of albumoses mixed with the pep-
sin. In order to get this latter approximately pure, the diges-
tion is continued for three weeks, by which time the greater
proportion of the proteins are converted into peptones. On
saturating the fluid with ammonium sulphate, the whole of
the pepsin is thrown down contaminated only with a slight
trace of unconverted albumoses. This precipitate mixed with
0'4 per cent. HCl gives a powerful artificial gastric juice.
The simplest method is however to extract the fresh mucous
membrane with glycerin. A few drops of the glycerin extract
added to dilute HCl makes an effective digestive mixture.

Action of Gastric Juice on the Food

The chief action of gastric juice is on proteins, which it
converts into albumoses and peptones. This action is easily
studied if we take some washed fibrin and put it in 0*2 per cent,
hydrochloric acid. In this acid the fibrin swells up and
becomes transparent, but does not dissolve, even though kept
at 40" C. for some time. If now to the swollen-up mass we
add some gastric juice, or a few drops of glycerin-extract of
gastric mucous membrane, the fibrin is speedily dissolved
and a clear solution results. Neutralisation of the fluid with
alkali throws down nearly the whole of the protein present as
acid albumen. If however the action be long continued, the
neutralisation precipitate becomes less and less, and the fluid
contains chiefly albumoses with a little peptone. These may
be shown to be present by the following tests.

Nitric acid gives a precipitate which dissolves on heating
and reappears on cooling.

Caustic potash and a trace of copper sulphate give a pink
colour, which turns to violet on the addition of more copper
sulphate — biuret reaction.

320 PHYSIOLOGY

Saturation with ammonium sulphate gives a copious
precipitate of albumoses. If tliis be filtered off, the filtrate
contains a small amount of peptone. To produce any large
quantity of peptone the gastric juice must act for a consider-
able length of time.

The stages in the action of gastric juice on proteins are
therefore —

Coagulable protein.

Syntonin or acid albumen.

Albumoses.

Peptones.

The action of gastric juice on proteins resembles that
of ptyalin on starch in that it consists of a series of hydro-
lytic changes, converting the large indiffusible coagulable or
coagulated molecule into a number of smaller non-coagulable
more soluble and more diffusible molecules. The study of
the disintegration products of proteins (p. 33) has shown
however that they are much more complex in constitution
than the starches, and hence we find a greater variety among
the first products of their hydrolysis. The number of
albumoses and peptones is probably large, but we are able to
group them into fairly definite classes according to the stage
in digestion at which they are produced. In the process of
digestion the proteins undergo progressive disintegration, so
that the first products, the primary albumoses, are large
molecules reacting to saline precipitants like globulins, while
the latest stages, the peptones, are small molecules, not
precipitated by neutral salts, and, relatively to proteins,
difl'usible. The stages in the peptic digestion of fibrin are
shown in the following table :

Fibrin.

I
Soluble globulin, coagulating at 56° C.

I
Acid albumen.

Primary albumoses (proto- and hetero-albumose).

Secondary albumoses (deutero-albumoses).

I
Peptones.

THE MECHANISMS OF DIGESTION 321

Kiihne's method for the separation of these bodies from a gastric digest of
fibrin can be carried out in the following way :

Neutralise — Acid albumen precipitated.

Boil in slightly acid reaction — Coagulable proteins precipitated.

The filtrate contains only albumoses and peptones.

Saturate filtrate with solid NaCl ; all the hetero-albumose and the greater
part of the proto-albumose are precipitated. This precipitate is collected,
dissolved in water, and dialysed. As the salt passes out the hetero-albumose
is precipitated, being insoluble in pure water, while the proto-albumose remains
in solution and can be precipitated by concentration and addition of absolute
alcohol.

The filtrate from the i^rimary albumoses is treated with a little glacial
acetic acid previously saturated with NaCl. This throws down the last traces
of proto-albumose and a little deutero-albumose. The precipitate is filtered
off, and the filtrate saturated at boiling temperature with ammonium sulphate,
which precipitates all the deutero-albumoses. This precipitate is filtered off
and concentrated to separate off the greater portion of the Am.,SO,. The
last traces of Am^SO^ are got rid of by the addition of baryta, and after filtering
off the BaSO^ precipitate, and boiling off the ammonia, the peptones are
precipitated by adding a large excess of absolute alcohol, or by means of
phosphomolybdic acid.

By means of fractional precipitation with ammonium sulphate, Pick has
separated three deutero-albumoses, which are designated as A, B, and C
deutero-albumose. These can be further subdivided by treatment with alcohol,
which dissolves certain of the albumoses and leaves others. Among the pro-
ducts so separated may be mentioned a thio-albumose, rich in sulphur, and
a glyco-albumose, containing the greater part of the carbohydrate moiety of the
original protein. These various bodies also differ according to the nature of
the monamino-acids and the amount of basic nitrogen they yield on hydro-
lysis. The peptone obtained by Kiihne's method may also be divided into
a peptone insoluble in alcohol which contains carbohydrate, and a peptone
soluble in alcohol which yields no carbohydrate radicle on hydrolysis, and
therefore does not give the Molisch reaction.

The later stages of gastric digestion are by no means
rapid, so that even after twenty-four hours' digestion the
greater portion of the proteins are found in the form of
albumoses.

Gastric juice acts in the same way on insoluble coagu-
lated proteins, dissolving these and converting them into acid
albumen, albumoses, and peptone.

Gelatin is converted by gastric juice into bodies known as
gelatin peptones, and in this conversion loses the power of
forming a jelly when cold.

Collagen, the constituent of the connective tissues from
which gelatin is obtained on prolonged boiling, is also digested
by gastric juice, giving rise to the same end-products as
gelatin.

21

322 PHYSIOLOGY

In this way the connective tissue binding together the fat-
cells of adipose tissue is broken up and dissolved, and the
fat is set free in a liquid form, ready to be acted on by the
pancreatic juice.

Another important function of the gastric juice depends
on the fact that dilute hydrochloric acid acts as an anti-
septic. Meat and fibrin may be kept for several days in
gastric juice without undergoing decomposition. If however
the acid be neutralised, decomposition sets in rapidly on
exposure to air, and at the end of twenty-four hours the
mixture has a foetid odour, and is found to be swarming with
bacteria. This action is of great importance in the normal
life of the individual. The microbes which have been shown
to be the causes of typhoid and cholera are destroyed by
gastric juice. Hence there is little likelihood of contracting
these diseases unless the secretion of gastric juice be insuf-
ficient, or the acid neutralised by the presence of alkalies or
rendered inert by too much dilution.

On starches and fats gastric juice has no action. Inges-
tion of large amounts of cane-sugar gives rise to a free
secretion of mucus on the surface of the gastric mucous
membrane, and this mucus is said to contain an invert fer-
ment which has the power of converting cane-sugar into
dextrose and laevulose. A certain amount of inversion
must also be caused by the action of the dilute HCl at
the body temperature. The same factor would convert
some of the maltose formed by the salivary digestion into
dextrose.

Circumstances affecting activity of gastric juice. — Gas-
tric juice is most active at about 40° C. At 0° its action is
indefinitely suspended. If boiled the ferment is destroyed.
The action goes on most rapidly when the proportion of HCl
present is 0*4 per cent. ; larger amounts of acids hinder its
action. Neutralisation stops the action altogether ; and if
the juice be rendered slightly alkaline and be kept at the
temperature of the body for a short time, its activity is per-
manently destroyed. Its action is also hindered if the pro-
ducts of its activity be allowed to accumulate to a large extent.
In the stomach this is guarded against by the continual
absorption through the gastric mucous membrane of the
albumoses and peptones as they are formed.

THE MECHANISMS OF DIGESTION 323

Action of Gastric Juice on Milk

Milk, which is the sole diet of the infant, is in itself a
whole food, and contains representatives of all five classes
of foodstuffs — proteins, fats, carbohydrates, salts, and water.
The chief protein of milk — caseinogen — is a body allied to
the nucleo-albumens. From the gastric mucous membrane,
especially in young animals, a ferment may be extracted
known as rennet ferment or rennin. On adding a few drops
of rennet solution to milk, and warming the mixture to about
40" C, it sets into a solid mass, so that the vessel may be
inverted without spilling the contents. On allowing the clot
or curd to stand it shrinks, enclosing in its meshes the
greater part of the fat-globules of milk, so that the clot floats
in an almost transparent fluid (whey). This clotting depends
on a change induced in the caseinogen of the milk under the
action of the ferment.

Pure caseinogen may be prepared in the following way.
A litre of ' separated ' milk {i.e. milk that has been freed from
cream by the use of a centrifuge) is diluted with 9 litres of
distilled water in a tall glass vessel and 10 c.c. of glacial acetic
acid added and the mixture stirred. A flocculent precipitate
of caseinogen is produced, and rapidly sinks to the bottom of
the vessel. The precipitate is collected, pressed between
linen, and rubbed up in a mortar with 20 c.c. of ammonia, and
water added to 5 litres. The solution is allowed to stand for
some hours, any fat which may rise to the top being skimmed
off. Acetic acid is added as before, and the resultant pre-
cipitate is washed several times by deeantation with distilled
water, and finally collected on a filter and pressed free of
fluid. This precipitate may be dissolved in weak soda or
potash, forming a clear solution. If it be dissolved in lime-water
an opalescent solution is formed. If rennet be added and the
mixture allowed to stand at 40° C, a clear colourless clot of
casein is produced. This act of clotting, just as the clotting of
blood, is intimately dependent on the presence of a neutral salt
of lime. If the precipitate of caseinogen be washed till all lime
salts are removed, addition of rennet causes no clotting ; but
the mixture of caseinogen and rennet clots at once on addition
of calcium phosphate or chloride.

324 PHYSIOLOGY

Thus in clotting of milk two processes are concerned :

1. A conversion of caseinogen into some other body which
may be called soluble casein.

2. A combination of this soluble casein with a lime salt
to form insoluble casein, which is precipitated in a gela-
tinous form.

These facts are well shown by the following experiment
of Ringer, Two test-tubes are taken, a and h, containing
a solution of pure caseinogen free from lime. To a rennet
ferment is added, and to h a solution of calcium chloride ;
and the two tubes are kept at 40° C. for some time. No
visible reaction takes place. If a be now boiled, so as to
destroy the rennet ferment present, and on cooling a few
drops of calcium chloride be added, clotting occurs. In
this experiment the rennet ferment has evidently produced
some change in the caseinogen although no clotting took
place, since the boiled fluid needs only the addition of lime
salt to make it clot. The fact that h did not clot shows
that lime salts are without effect on a solution of caseinogen
which has not been previously exposed to the action of rennet
ferment,'

The Secretion of Gastric Juice

The functions of the two different kinds of gastric glands
have been determined by cutting out a portion of the cardiac
or pyloric parts of the stomach, and sewing its edges to the
margins of the abdominal wound. The gap in the gastric
wall thus produced is closed by suturing the edges together,
so that the final result of the operation is that the stomach is
rather smaller, and there is a little cul-de-sac consisting of
either cardiac or pyloric mucous membrane communicating
with the exterior. Secretion may be excited by mechanical

' The student must be careful to distinguish between the curdling of milk
by rennet and its curdling by addition of acid, or when it becomes sour in con-
sequence of the development in it of lactic acid. In the former case the
curdling is a true clotting, and is due to the conversion of the soluble
caseinogen into the insoluble casein, in the same way as when fibrinogen is
converted into fibrin. When acid is added to milk the caseinogen is merely
precipitated, just as uric acid is precipitated by addition of HCl to a
sglution of a urate. And this precipitate can be dissolved up again as caseinogen
and ma4G to clot, {.e, caij be ppnverted into casein by the agency of rennet
fernjent,

THE MECHANISMS OF DIGESTION 325

irritation of this mucous membrane by the introduction of a
sponge or some food, and the juice may be collected. It is
better however to make the cul-de-sac as described on p. 317,
leaving the nervous connections of the mucous membrane
intact. Under these conditions the isolated portion of the
stomach secretes whenever food is taken by the mouth into
the main stomach, and the secretion may be regarded as
practically normal in all respects. It is then found that a
cardiac cul-de-sac contains free HCl and pepsin, and so has
the power of digesting proteins. A pyloric cul-de-sac, on the
other hand, yields a secretion which is neutral or slightly
alkaline, but which is shown to contain pepsin from the fact
that, on adding 0*2 per cent, of hydrochloric acid, the juice
is able to digest proteins. This shows that both cardiac and
pyloric glands yield pepsin, but only the cardiac glands
yield free hydrochloric acid. Since in both sets of glands
the central cells are the same, it is concluded that these cells
give rise to the pepsin, while the large oval parietal cells in
the cardiac end form the free hydrochloric acid.

Coincident with activity, changes take place in the central
cells analogous to those which we studied in the case of the
salivary glands. The central cells of the glands from a
fasting stomach {i.e. of an animal that has not taken food for
eighteen hours) are swollen and filled with granules. When
secretion occurs two zones can be distinguished, an outer
protoplasmic zone, free from granules, and an inner granular
zone, which becomes less and less marked as secretion pro-
ceeds. These granules consist of a zymogen, pepsinogen. If
the fresh mucous membrane be extracted with glycerin, much
less ferment is obtained than if the extraction be performed
after treatment of the mucous membrane with dilute acid.
The pepsinogen is further distinguished from the pepsin by
the fact that it is only slowly affected by a solution of sodium
carbonate, which very rapidly destroys pepsin. Thus if an
acid extract of the gastric mucous membrane be made alka-
line to the extent of 1 per cent, sodium carbonate, the whole of
the pepsin is destroyed within thirty seconds. On the other
hand a neutral watery extract of the membrane may be made
alkaline for two or three minutes, and on then adding HCl
to 0*2 per cent, it is found that the mixture has a strong
digestive action. The acid extract contains pepsin which is

826 PHYSIOLOGY

destroyed by the carbonate. The watery extract contains
chiefly pepsinogen and is therefore only slowly altered by the
treatment.

The secretion of gastric juice may be excited by direct
stimulation of the mucous membrane by the presence of
food, etc., in the stomach. We have evidence that a copious
flow of gastric juice may be excited through nervous channels,
either reflexly through the mouth or in consequence of events
occurring in the brain. This reflex secretion is well shown
in the following experiment : — The oesophagus of a dog is
divided in the neck, and the two ends stitched to the wound
80 that they open exteriorly. At the same time a gastric
fistula is made. The dog is fed and kept in good condition
by the introduction of milk into the lower end of the oeso-
phagus, or by the direct introduction of food into the stomach.
When the animal has quite recovered, he is starved for nine
hours and is then allowed to eat meat. The dog eats greedily,
and, since the food cannot reach the stomach but tumbles
out by the opening of the oesophagus in the neck, will go
on eating for a very long time. Directly the dog begins
to eat, a copious secretion of gastric juice is obtained, as
much as 300 c.c. of pure gastric juice being poured out in
one hour, clear and colourless like water. The same eftect
may be produced by simply showing the dog a piece of
meat, and it is stated that the flow ceases as soon as the
dog realises that he is not intended to have the meat.
Pawlow, to whom we owe the above experiment, has shown
that the efferent nerve in the reflex, that is to say, the
secretory nerve to the stomach, is the vagus. If proper
precautions be observed, stimulation of the vagus causes
invariably a secretion of gastric juice.

In testing the action of the vagus on the gastric secretion, we have to bear
in mind that the activity of the gastric glands is reflexly inhibited by al
painful stimuli, and is abolished by any stoppage of the blood-flow or by the
action of anaesthetics. The experiment is therefore carried out in the follow-
ing way : — On one day the gastric fistula is established, and one vagus in the
neck divided and ligatured, the ligature being allowed to hang out of the
wound. Four days later the animal is placed in an upright position, the
vagus drawn out of the wound and stimulated with induction-shocks at the
rate of one or two a second. The animal is not anaesthetised and the experi-
ment is unattended with pain. The cardio-inhibitory fibres are degenerated in
consequence of the section, so that the stimulation does not alter the blood-
pressure in any way. After a latent period of four or five minutes, gastric

THE MECHANISMS OF DIGESTION 327

juice begins to drop from the cannula in the fistula, and the secretion
can be obtained as often as the nerve is stimulated. Section of both vagi stops
the reflex secretion of gastric juice normally evoked by the sham feeling
described above.

There are however two sets of factors involved m the
normal secretion of gastric juice. The more important is
the nervous mechanism described above, set into action from
the mouth or the cerebral cortex under the influence of appetite,
and having as its efferent channel the vagus nerve. This
mechanism is destroyed by section of both vagi. It is then
observed that introduction of food into the stomach evokes
a secretion of juice, which comes on one to two hours later,
and lasts a considerable time. If a diverticulum of the stomach
has been made, introduction of food into the main stomach
excites in this way secretion in the isolated cul-de-sac.
Edkins has recently shown that the mechanism of this latter
secretion is chemical. Under the influence of the food, some
substance, a chemical messenger or ' hormone,' is produced in
the pyloric mucous membrane, is absorbed into the blood, and
carried to all parts of the mucous membrane, in which it
acts as a specific excitant of the gastric glands, evoking a
secretion of gastric juice.

828

PHYSIOLOGY

Section 4
PANCKEATIC JUICE

The food, after being acted on by the gastric juice, is
gradually passed on as the fluid chyme into the duodenum,
the first part of the small intestine. Here it is subjected to
the action of three secretions, the pancreatic juice, the bile,
and the succus entericus.

The pancreas lies in the curve formed by the duodenum,
and pours its secretions into that viscus by a duct which

Fm. 171.

O

^,{

k

&j

- d

'"d

-■^ f

p.<^/"

Section of human pancreas (Bohm and v. Davidoft'). x 450. a, cell-
nest between acini ; b, connective tissue ; c, large duct ; d, d,
alveoli; e, duct passing into alveoli; /, inner granular zone of
acinus.

joins the duct from the liver and opens at a pomt about two
or three inches below the pylorus. It is a tubulo-racemose
gland, somewhat similar to a salivary gland. Its tubules
however are much longer than those of the parotid. The
tubules are lined with polyhedral cells, the inner two-thirds of
which are granular, while the outer third is free from granules
and stains darkly with baematoxylin. Activity is associated
with a discharge of these zymogen granules, so that the cells

THE MECHANISMS OF DIGESTION 829

shrink and become clearer. At the same time there is a growth
in the protoplasm, so that in a discharged gland nearly the
whole of the cell stains with haematoxylin.

On examining a stained section of pancreas under the microscope, we rarely
fail to see here and there small circumscribed patches of epithelioid cells which
have very little athnity for dyestuffs, and therefore appear as lighter areas in
the section (a, fig. 171). The cells are often arranged in short columns or
clusters, and but little trace of an alveolar structure can be made out. These
structures, which are known as the ' islets of Langerhans,' have often been
regarded as a special tissue planted in the midst of the ordinary secreting tissue
of the pancreas. It has been shown by Dale however that the number of
these islets is markedly increased by activity, and that, in a gland which has
been thoroughly exhausted, the larger part of the secreting substance loses its
staining properties and becomes converted into islet tissue. One must there-
fore regard these islets as a phase in the life history of the secreting
cells, and as representing an extreme stage of exhaustion of these cells.
Whether they recover their staining properties and resume their secretory
activity, or whether they are removed altogether to make room for newly
formed glandular tissue, is not yet thoroughly made out, though the fact that
at a certain period of foetal life all the pancreatic cells have the appearance of
islet cells is certainly in favour of the former alternative.

In order to collect pancreatic juice for examination and to
investigate the conditions of its formation, it is necessary to
make a pancreatic fistula. To make a permanent fistula, the
abdomen (of a dog) is opened in the middle line, the first part
of the duodenum drawn up to the surface, and a lozenge-
shaped piece of the duodenal wall cut out, in such a position
as to include the orifice of the chief pancreatic duct. The
margins of the wound in the gut are then stitched together so
as to restore its continuity, and the little piece of excised
duodenal wall is stitched into the opening in the abdominal
wall. When the wound is healed, the nipple-like orifice of
the duct is seen on the surface of the abdomen in the
middle of a small red patch of mucous membrane. To
make a temporary fistula, it is only necessary to expose
the duct at its entry into the duodenum and insert into it a
small cannula, connected with a rubber tube through which
the juice is allowed to flow into a suitable vessel.

In an animal with a permanent fistula no flow of juice
occurs so long as it is in a fasting condition. At a variable
period after a meal has been taken, a flow of juice begins and
continues for several hours. It can be shown that the flow
of juice follows immediately the entrance of the acid chyme

380 PHYSIOLOGY

into the duodenum, no flow being excited so long as the
food remains in the stomach. The flow of juice can in
fact be evoked at any time by the introduction of weak acid
{e.g. 0*4 per cent. HCl) into the duodenum or the upper part of
the small intestine. No effect follows the introduction of acid
into the lower part of the ileum or into the large intestine.
The effective stimulus to pancreatic activity is therefore the
presence of acid in the upper part of the small intestine.

How is this stimulus conveyed to the pancreatic cells ?
It was thought by Pawlow and other physiologists that the
medium of transmission here, as in the case of the salivary
glands, was the nervous system— either the central nervous
system by means of the vagi, or peripheral collections of
ganglion cells round the abdominal vessels and in the
pancreas itself through the fine nervous filaments which pass
between these and the intestinal wall. This idea however
had to be abandoned when it was found that introduction of
acid into a loop of small intestine, entirely freed from nervous
connection with the rest of the body, produced a flow of pan-
creatic juice as profuse as that obtained from a loop of normal
intestine. In the former case the only connection of the
intestine with the pancreas was by means of the blood.

We must therefore conclude that the stimulus is a chemical
one, produced in the mucous membrane by the action of the
acid and carried thence to the pancreas in the blood stream.
If the mucous membrane be scraped, and the scrapings
rubbed up with dilute hj^drochloric acid, and the mixture be
then boiled, neutralised, and filtered to separate the proteins,
a clear colourless filtrate is obtained, which, on injection in
small quantities into the blood stream, evokes a copious
flow of pancreatic juice. A watery or normal saline extract of
mucous membrane has no effect. These facts prove that the
mucous membrane of the upper part of the small intestine
contains a body, which may be cQ\\e([ prosecretin. Under the
influence of dilute acids this body is converted into or gives
off another substance, secretin, which is a specific stimulus
for the pancreatic cells. This secretin is discharged by the
cells, not into the intestine, but into the blood stream. By
the blood it is carried to all parts of the body, and on passage
through the pancreas, excites secretion of pancreatic juice.

Secretin is apparently a body of relatively simple con-

THE MECHANISMS OF DIGESTION 331

stitution. It is soluble in acid, neutral, or alkaline solutions,
or in alcohol. It is diffusible, and is not d-estroyed by boiling.
It is not a ferment. It has not yet been isolated.

Characters and Actions of the Pancreatic Juice.

The juice obtained from a permanent fistula after a meal,
or from a temporary fistula as the result of introduction of
acid into the duodenum or the injection of a solution of secre-
tin into the blood stream, is a clear colourless liquid, strongly
alkaline from the presence of sodium carbonate. It contains
from 1-5 to 3-5 per cent, total solids, of which about 0*5 to 2*5
are coagulable proteins. It has a digestive action on all three
classes of foodstuffs. It converts starches into dextrin and
sugar by means of a ferment, amylopsin ; it hydrolyses fats by
means of its ferment, steapsin ; and after entry into the gut it
contains a strong proteolytic ferment, trypsin. If however
the juice be collected by a cannula in the duct, so as to pre-
vent any contamination by the intestinal mucous membrane,
it has only slight proteolytic powers, taking twelve hours to
dissolve fresh fibrin, and l)eing without action on coagulated
egg albumen or gelatin. The addition of a few drops of
succus entericus or a fragment of intestinal mucous membrane
into the fresh juice, rapidly converts it into one of the most
powerful proteolytic agents with which we are acquainted.

The proteolytic ferment contained in the juice under these
circumstances is known as trypsin. The juice as secreted
contains a precursor of this ferment, known as trypsinogen,
which, under the action of a ferment, cnterokinase, secreted
by the intestinal mucous membrane, is converted into
trypsin.

Glycerin extracts of a fresh pancreas have a marked
amylolytic action, but have practically no proteolytic action
unless the extract has been contaminated with mtestinal con-
tents containing enterokinase, the smallest trace of which will
in time convert almost any quantity of trypsinogen into
trypsin. The action of pancreatic extracts on fats is only
observed in perfectly fresh extracts, the steapsin apparently
undergoing rapid spontaneous destruction.

332 PHYSIOLOGY

Action on Proteins

Proteins are converted by trypsin into albumoses and
peptones, as in the case of the gastric juice. Trypsin how-
ever is only active in an alkahne or neutral medium, and
is inert in the presence of an acid. If fresh fibrin be
digested with this juice, it does not swell up but is gradually
eroded and dissolved at the edges. The first product of its
action is not acid- but alkali-albumen. Another important
difference of this ferment from pepsin lies in the fact that it
carries on the process of decomposition still further, causing
a profound disintegration of the protein molecule, resembling
that brought about by the action of boiling hydrochloric acid.
The final results therefore of tryptic digestion are a number
of bodies of comparatively small molecular weight, belonging to
the series of bodies described as amino-acids and hexone bases.

In consequence of the much greater activity of trypsin as
compared with pepsin, the first stages of proteolysis are much
more rapid with the first-named. At no period of the process
is it possible to detect the presence of primary albumoses,
the alkali-albumen being directly converted into deutero-
albumoses and peptones.

The end-products of pancreatic digestion include nearly
the whole series of monamino- and diamino-acids which can
be obtained by the action of acids on proteins.

These may be enumerated as follows : —

A. Mono-amino-acids.

I. Monobasic acids of fatty series.
Glycine (amino-acetic acid).
Alanine (amino -propionic acid).
Serine or oxyalanine (oxyamino-propionic acid).
Amino-valerianic acid.
Leucine (amino-isobutyl-acetic acid).
Isoleucine (amino-caproic acid).

II. Dibasic acids.

Aspartic acid (amino-succinic acid).
Glutamic acid.

III. Benzene derivatives.
Phenylalanine.
Tyrosine (oxyphenyl-alanine).

THE MECHANISMS OF DIGESTION 333

B. Heterocyclic compounds {i.e. ring compounds like
benzene, but containing both C and N in the
closed ring.
Proline' (pyrrolidine carboxylic acid^.
Oxyproline (oxypyrrolidine carboxylic acid).
Tryptophane (indolamino-propionic acid),

C. Diamino-acids and allied bodies, strongly basic in
character (the * hexone bases ').
Lysine (diamino-caproic acid).
Arginine (guanidine amino-valerianic acid).
Histidine (imidazol amino-propionic acid).
Diamino-trioxydodecoic acid (derived from a 12-
carbon acid).

D. Sulphur-containing body.

Cystine (derived from amino-thio-lactic acid).

Not all of these are to be obtained from every protein.
All proteins however yield a large number of different amino-
acids.

Two of these substances, namely, leucine and tyrosine, have
long been known, owing to the ease with which they may be
separated from a pancreatic digest.

Leucine belongs to the fatty series, being amino-isobutyl-
acetic acid —

CH3CH,
\/

CH

i
CH2

I
CH.NH,

I
COOH.

When pure it crystallises in white transparent plates, but
in the impure state, as it separates out on concentrating
a pancreatic digest, it forms microscopic globules with radial
or concentric striation, often spoken of as * leucine cones '
(Fig. 172). About 10 to 20 per cent, of leucine may be
obtained from most proteins.

' Phenylalanine and proline a,i'e not found frge in a pancreatic digest, being
combined to form a polypeptide.

334 PHYSIOLOGY

Tyrosine is an amino-fatty acid in combination with an
aromatic group. Its constitution is shown by its formula, its

C.,H,NH.,COOH
/\

\/
OH

full name being para-oxyphenyl-a-amino-propionic acid.

aromatic moiety amino-fatty acid.

It crystallises in long slender needles aggregated into
sheaves and rosettes (Fig. 173). It is very sparingly soluble
in water and alcohol, and so is easily separated from pancreatic

Fig. 172. Fig. 173.

Leucine 'cones' (imperfect crystals) Tyrosine crystals (Frey).

(Frey)

digests, often crystallising out spontaneously at the bottom
of the liquid. It forms only 2-3 per cent, of the original
protein.

Aspartic acid (amino-succinic acid CoH,(NH.J.(COOH).^) is also formed in
small quantity in the pancreatic digestion of proteins. It forms, however, the
greater part (35 per cent.) of the amino-acids obtained by digestion of the
proteins of wheat.

Antipeptone is a name which has been given to the
precipitate obtained by treating the digest with phospho-
molybdic acid, after separation of the chief amino-acids.
Although it gives the biuret test, it does not give any colora-
tion with Millon's reagent, and is not properly included
in the class of peptones. It is probably a mixture of bodies,
including the bases, lysine and arginine, the former being
diamino-caproic acid C,r,H,, (NH^).^ COOH, and the latter a
body analogous to creatine and giving rise, like creatine, to

THE MECHANISMS OF DIGESTION 335

urea on heating with baryta water. In addition to these
bases a small amount of ammonia is set free during the
proteolysis.

A certain proportion of the nitrogen is in the form of a polypeptide which
on further hydrolysis yields several amino-acids of the fatty series as well as
the greater part of the phenyl -alanine and proline contained in the original
protein.

Another constant product of the pancreatic digestion of proteins is trijpto-
pliane, a body belonging to the aromatic group, and giving a typical red
colour with bromine. To the presence of this group in proteins is due the
reaction of Adamkiewicz and Hopkins, viz. a purple colour on treatment with
strong sulphuric acid and glyoxylic acid, or glacial acetic acid contaminated with
the latter substance.

The changes involved in the pancreatic digestion of pro-
teins may therefore be represented as follows :

Fibrin

Soluble protein (globulins)

Alkali-albumen

I
Deutero-albumoses

Peptones

Amino-acids Hexone bases Tryptophane, Polypeptide

(leucine, tyrosine, etc.) (lysine, arginine, etc.) etc.

Cystine

In the case of coagulated protein, there is apparently
no formation of soluble proteins or alkali-albumen, the first
product of proteolysis which can be separated being deutero-
albumose.

Until recently, it was thought that the small molecules,
which constitute the end products of pancreatic digestion,
must be practically valueless for the purposes of nutrition,
and that the main use of the energetic action of the trypsin
was the gain of time in the first stages of proteolysis. It must
be remembered however that we employ as food numbers of
different kinds of proteins, whose constitution diverges con-
siderably from that of the proteins building up our tissues.
A man can make muscle protein out of the most various kinds
of vegetable protein, whether from peas, beans, or wheat. For
this conversion to take place the protein molecule must be first
resolved into its constituent parts, out of which a new and
different protein can be built up. A thorough disintegration

336 PHYSIOLOGY

is therefore a necessary preliminary to the assimilation of
any foreign form of protein, and it is this thorough dis-
integration that is effected by the pancreatic juice, working
with the succus entericus. Loewi has succeeded in keeping
dogs in health, and in a state of nitrogenous equilibrium, for
some time on a diet consisting, so far as its nitrogen was
concerned, entirely of the ultimate products of pancreatic
digestion.

Since the bacteria of putrefaction thrive readily in a
slightly alkaline solution of protein such as pancreatic juice,
care must be taken in all experiments with this juice to pre-
vent putrefaction. To this end thymol or 1 per cent, sodium
fluoride may be mixed with the solution. If this precaution
be omitted, the mixture at the end of twenty-four hours has
a foul odour, and is found to be swarming with bacteria, under
the agency of which the proteins are further split up, with
the formation of many amino-acids, free fatty acids, and
aromatic bodies such as phenol, indol, and skatol. To the
presence of the last two bodies is due the horrible faecal odour
of a pancreatic digestion -mixture which has been allowed to
stand without the addition of an antiseptic. These aromatic
substances are produced from the tryptophane (indoxyl amino-
propionic acid), which is one of the primary decomposition
products of proteins.

Gelatin is affected by pancreatic juice in the same way as
by gastric juice, being converted into gelatin-peptones, which
do not gelatinise on cooling. This juice however is unable
to dissolve collagen, the chief constituent of the connective
tissues. Hence if the stomach of a dog be cut out, and the
lower end of the cesophagus sewn to the upper end of the
duodenum, it is found that considerable quantities of fat pass
undigested through the alimentary canal, since the connective
tissue binding fat-cells together can no longer be dissolved by
a stomachless dog.

Action on Carbohydrates

The action of the pancreatic juice on starch is similar to
that of ptyalin, but is more rapid. It is still further accele-
rated by the addition of small quantities of bile. The stages
of conversion are the same as in the case of ptyalin, the end-

THE MECHANISMS OF DIGESTION 337

products being acliroodextrin and maltose. If the action be
long continued, the process of hydrolysis may go on to the
formation of dextrose, but the amount of this body formed is
in all cases very slight, and is probably due to the presence of
traces of the special ferment, maltase, in the pancreatic juice.

Action on Fats

Fresh pancreatic juice contains a ferment which has a
hydrolytic action on neutral fats, splitting them up into
glycerin and a free fatty acid, thus :

C3H,(C„H3,02)3 + 3H,0 = C3H,(OH)3 + 3HC„H3,0,.

Tripalmitin (neutral fat). Glycerin. Palmitic acid.

This decomposition takes place in the presence of the
alkaline salts of the pancreatic juice and bile. The free
fatty acid formed by the ferment action combines with
the alkali present, displacing the CO. to form a soap. The
presence of soap in the solution enables it to hold all the
rest of the neutral fat in suspension. Thus if a drop of
rancid oil {i.e. one containing free acid) be allowed to drop on
to the surface of a 1 per cent, solution of sodium carbonate,
the acid at the exterior of the drop unites with the alkali to
form a soap, which is immediately dissolved. The chemical
change and solution going on at the surface of the drop set
up in the surrounding fluid diffusion-currents which carry off
little particles of the neutral fat. These immediately become
coated with a layer of soap which prevents them running
together again. So we see a white cloud appearing round
the drop of rancid oil, and under the microscope the cloud
is observed to consist of innumerable tiny droplets of fat
suspended in the alkaline liquid. A single shake causes the
whole drop to break up into these droplets, the milky fluid
thus formed being spoken of as an emulsion. In this way the
pancreatic juice has the power of emulsifying neutral fats.

This fat-splitting action may go on in a neutral or slightly
acid medium, and so is not subject to such restrictions as are
the proteolytic or amylolytic functions of the pancreatic juice.

This juice also contains a ferment similar to rennet, which
has the property of curdling milk. It is probably of no
physiological importance.

22

338 PHYSIOLOGY

Section 5
THE BILE

The bile is the product of secretion of the Hver. This
organ differs in structure from all other glands of the body,
the cells being so numerous and pressed together around
the capillary meshwork that their primitive arrangement
as secreting tubules is no longer to be made out in the adult
liver.

The liver has a double blood-supply : the portal vein,
which supplies a rich capillary anastomosis round every liver-
cell, and carries venous blood from the alimentary canal ; and
the hepatic artery, which carries oxygenated arterial blood,
and supplies chiefly the connective tissue surrounding the
bile-ducts and blood-vessels in the divisions between the
lobules, known as Glisson's capsule.

The lobules are about 1-5 mm. in diameter and consist
of the liver-cells, blood-vessels, and bile-capillaries, and are
bounded by the connective tissue forming Glisson's capsule.
The branches of the portal vein run in this connective tissue
at the periphery of the lobules, where they are termed inter-
lobular veins. From these veins a rich plexus of capillaries
runs towards the centre of the lobule, where they join a small
vessel known as the intralobular vein. The intralobular veins
unite to form the sublobular veins, which pour their contents
into the hepatic veins. These at the hinder border of the
liver run into the inferior vena cava, which carries their blood
into the heart.

Corresponding with the semi-arterial functions of the
portal vein, we find the muscular tissue in its walls better
developed than is the case with most veins. The portal vein
is also well supplied w^ith vaso-motor nerves, which leave the
cord by the lower dorsal roots and run in the great splanchnic
nerves. Since the pressure in the portal vein is low (about
10 mm. Hg), any constriction of the portal vein will help to
raise the arterial blood-pressure, not so much by increasing
the peripheral resistance as by lessening the total capacity of
the vascular system.

THE MECHANISMS OF DIGESTION

339

The whole of the space between the capillaries is filled with
liver-cells, which are polygonal in shape, and about 0'02 mm.
across. They consist of granular protoplasm with a large

Fig. 174.

Section of injected liver, showing the division into lobules. The
interlobular branches of the portal vein (F P) are connected with
the intralobular branches of the hepatic vein {H V) by numerous
radiating capillaries. Below is a portion of the same, more highly-
magnified, o, liver cell ; n, nucleus ; 6, blood-capillaries ; c, bile-
capillaries.

rounded nucleus in the centre and may often contain hyaline
masses of glycogen (Fig. 175). The bile-ducts, which run at
the periphery of the lobules, receive the bile secreted by the
liver-cells, by means of a number of very fine branching

340

PHYSIOLOGY

canals, known as the bile-capillaries. The latter may in
section be seen to be situated between the adjacent flat sides
of the liver-cells, as far removed from a blood-capillary as
possible, their walls being formed by the liver-cells themselves.
The bile-ducts join to form the hepatic duct, which leaves the
liver at the transverse fissure and passes to the duodenum,
giving off on its way a diverticulum, the gall-bladder, con-
nected with the main duct by a special canal, the cystic duct.
This subordination of the glandular to the vascular arrange-
ments of the liver betokens a similar subordination of the
secreting function of the liver. Although the bile is of im-
portance both as an excretion and as a digestive secretion, its

Fig. 175.

a, hepatic cells containing glycogen ; b, hepatic cells from which
the glycogen has been removed; c, a pi ejiaration similar to b,
but from a liver containing originally much less glycogen.
(Heidenhain.)

formation represents but a small part of the total activities of
the liver, which is the great chemical factory of the body,
modifying in the direction of assimilation and dissimilation
the various products of digestion brought to it by the portal
blood. An animal may survive complete obstruction of the
bile-ducts for many months, wheieas abolition of the total
liver functions is followed by death within a few hours.

The secretion of bile is a continuous process, but it does
not flow directly into the intestine, being stored up during
fasting in the gall-bladder, whence it is discharged by the
contraction of this viscus when the acid chyme passes the
orifice of the common bile-duct.

The discharge of bile into the intestine is greatest about

THE MECHANISMS OF DIGESTION 841

three to five hours, and agam about thirteen hours, after the
ingestion of food. The secretion of bile is much quickened by
the injection of secretin into the blood stream : a fact that
will account for the increased secretion observed within the
first few hours after the taking of food. Since bile is an
important adjuvant to the pancreatic juice, it is evidently of
advantage that its secretion should be increased by the same
mechanism that evokes the secretion of the pancreatic juice.

Bile as obtained from the gall-bladder is dark brown or
greenish in colour. It is alkaline and slimy from the presence
of mucin. Its specific gravity varies from 1010 to 1040.
The following table represents the average composition of
human bile taken from the gall-bladder.

100 parts contain —

Water 85 parts.

Bile salts 10 ,>

Fats, lecithin, and cholesterin . . 1 part.

Mucus and pigment ... 3 parts.

Inorganic salts . . about 1 part.

Besides these constituents, bile contains gases, especially
carbon dioxide, and traces of soaps.

If the bile be collected as it is secreted by the liver, by
inserting a cannula in the hepatic duct, it is found to contain
a larger percentage of water and little or no mucin. It is
evident therefore that during its stay in the gall bladder the
bile loses its water, and acquires mucin, which is secreted by
the mucous membrane of the gall-bladder. •

The bile salts are two in number — glycocholate and tauro-
cholate of soda. The relative amounts of the two salts vary
in difierent animals, the taurocholate being as a rule most
abundant in carnivora, and the glycocholate in herbivora.
In human bile, glycocholate forms nearly the whole of the
bile salts present.

The bile salts may be extracted in the following way : —
Bile is mixed into a paste with animal charcoal, and the
mixture dried, pounded up, and extracted with absolute
alcohol and filtered. On adding ether to the alcoholic

' The greater part of the muein-like substance occurring in ox-bile, and pre-
cipitated by acetic acid, is really a nucleo-albumen. Human bile on the other
hand contains true mucin.

34'2 PHYSIOLOGY

filtrate, and allowing it to stand, a crystalline precipitate is
produced, consisting of the two bile salts. These have a
bitter taste, and are easily soluble in water. Their presence
in a fluid may be shown by Pettenkofer's reaction.

Addition of a drop of cane-sugar solution and excess of concentrated
sulphuric acid to a solution of bile salts gives a purple colour, due to the inter-
action oifurfurol, produced by the action of the sulphuric acid on the cane-sugar,
with cholalic acid, the common constituent of both bile acids. This colour
may be interfered with by the dark-brown colour produced by the charring of
the sugar with the sulphuric acid. Either of the following ways may be adopted
to obtain a good purple reaction :

A. The bile and sugar are shaken up in a test-tube until the upper part of the
tube is filled with froth. If the concentrated sulphuric acid be no\v poured down
the side of the tube, the froth is stained a purple colour where it comes in
contact with the acid.

B. A porcelain capsule is rinsed out successively with solutions of bile salts,
cane sugar, and dilute sulphuric acid (25 per cent.). On warming the capsule
gently over a flame, water is driven off from the thin film of dilute acid, and
the concentrated acid thus produced acts on the thin film of sugar and bile
salts, causing a brilliant purple colour of the whole of the inner surface of the
capsule.

Glycocholic acid is a conjugated acid, which on hydro-
lysis splits up into glycine (amido-acetic acid) and cholalic

acid (C,,H,oO,).

Taurocholic acid is also a conjugated acid, which can
be split up into taurine, an amido-acid containing a large
proportion of oxidised sulphur (amino-isethionic acid), and
cholalic acid.

The glycocholic acid can be obtained from the bile of some herbivora in a
free condition by adding a little hydrochloric acid and ether and shaking, when
the acid crystallises out in fine needle-shaped crystals.

(CHOH
Cholalic acid is a monobasic acid C.,,,!!^, -I (CH.,OH).,, and is obtained from

( COOH
either bile acid by prolonged boiling with strong solution of caustic soda.
Under the influence of acids or putrefaction (as in the intestine) it is converted
into an insoluble anhydride, known as dyslysin.
CH,.NH2
Glycine orglycocoll | is also obtained by the hydrolytic dissociation

COOH
of some proteins and of certain albuminoids such as gelatin and elastin. It
occurs in the urine conjugated with benzoic acid as hippuric acid.
/C,H,.NH2
Taurine BO^'C i^ found nowhere else in the body, and is the only

\0H
known example of a sulphonic acid which plays any part in the normal functions
of the body. It can be formed artificially from cystine, a normal constituent of
all proteins.

THE IVIECHANISMS OF DIGESTION 343

The mucin and nucleo-albumen present may be preci-
pitated by acetic acid. The precipitate is sokible in dilute
alkalies.

The bile-pigments are hiliruhin (brown) and hiliverdin
(green), and occur in the bile in combination with calcium.
The colour of the bile depends on the relative amounts of
these two pigments present. Biliverdin (CicHi^N204) may
be obtained on oxidation of bilirubin (CigHi^N.jOy).

The presence of bile-pigments may be proved by Gmelin's
test. A drop of bile on a white plate is treated with a drop
of yellow nitric acid. Where the two drops come in contact
a play of colours is produced, due to the formation of various
oxidation-products of bilirubin. These colours occur in the
following order — brown, green, blue, red, yellow. The end-
product of the reaction which gives the yellow colour is known
as choletelin.

The cholesterin present is probably kept in solution by
the bile salts. Under abnormal conditions, cholesterin may
be precipitated and may form concretions in the gall-bladder
(gall-stones). More rarely we meet with gall-stones con-
sisting of the bile-pigments in combination with alkaline
earths.

Actions of Bile

Bile contains small quantities of an amylolytic ferment
which has a feeble digestive action on starch. If added to a
mixture of starch and pancreatic juice, it materially hastens
the action of the latter.

On adding bile to an acid solution of albumoses and
peptones, such as the products of gastric digestion which come
through the pylorus into the first part of the duodenum, a
precipitate is produced, consisting of glycocholic acid, syntonin,
and albumoses.

One function of the bile then is to neutralise the gastric
juice and prepare the way for pancreatic secretion.

The alkaline salts of the bile can combine with the fatty
acids set free by the pancreatic juice to form soaps, and so
aid in the digestion and emulsification of fats. Bile also
assists in the absorption of fats by virtue of the bile salts it
contains. Oil will not run through a filter moistened with
water, but will do so if it be moistened with a solution of bile

344 PHYSIOLOGY

salts. The presence of bile salts lowers the surface-tension
between the oil and the water, so that in the intestine the drop-
lets of fat are able to come into intimate contact with the absorb-
ing surface of the epithelium, and with the digestive fluids.

The main importance of the bile however is as a fat
solvent. In a slightly acid medium the bile acids will dis-
solve 4 to 5 per cent, of free fatty acid. Bile has no solvent
action on neutral fats, but will dissolve soaps, including the
insoluble soaps of the alkaline earths. The importance of
bile for the absorption of fats is shown by the occurrence of
a large amount of undigested fat in the fasces on shutting off
the bile from the intestine. The fat-solvent action of the bile
salts in the bile is much aided by the simultaneous presence
in this fluid of lecithin and cholesterin in solution.

The presence of bile in the intestine is said to excite
contractions of the muscular walls, and so act as a natural
purgative. In the same way the muscular fibres of the
absorbent villi are stimulated by the presence of bile, and
contract, forcing the contents of the villus into the subjacent
lacteal.

Bile is often spoken of as an antiseptic, but this state-
ment must be qualified. The free bile acids, especially
taurocholic acid, have a pronounced antiseptic action. The
action is however lost when the acids are combined with
alkalies, as in the bile itself, which decomposes extremely
readily.

The Origin and Fate of the Biliary Constituents

The bile is to be regarded partly as a secretion, having an
important function in the digestion of fats, and partly as an
excretion— a means by which the eft'ete colouring matter of
the blood is got rid of.

The bile salts are formed by the liver, as is shown by the
fact that, after extirpation of the liver in frogs or birds, no
accumulation of these salts takes place in the body. If
however the bile-ducts be ligatured, bile salts are found in
the blood and in the urine. The glycine and taurine are
probably derived from protein disintegration, but we know
nothing concerning the precursors of cholalic acid. In the
intestine the bile salts play their part in the digestion of

THE MECHANISMS OF DIGESTION 345

fats, and are then for the most part reabsorbed, passing
along the portal vessels to the liver, where they are again
secreted, so that they can exert their functions over and
over again, A certain amount is split up in the intestine
into the amino-acids and cholalic acid, the former being
reabsorbed, and the latter being excreted with the faeces.

The bile-pigments are the products of disintegration of the
haemoglobin of the blood. They play no further part in the
body, and are excreted with the faeces in a slightly altered
form. It was long debated whether they were formed by the
liver, or whether some might not be formed in the blood itself
or in the other tissues from the disintegrated red corpuscles.
It is found that, after blood has been extravasated into the
tissues, the htemoglobin undergoes certain modifications, and
is converted into the body named haematoidin. Now hfema-
toidin is isomeric and probably identical with bilirubin, and
this fact was looked upon as furnishing strong evidence for
the haematogenous origin of bile-pigments. Experiment has
shown however that when blood-corpuscles are broken up
in the circulation (a process which is normally taking place
on a small scale) no bile-pigment is formed except by the
agency of the liver. A great breakmg-up of blood-corpuscles
and setting free of haemoglobin may be caused in animals by
the inhalation of arseniuretted hydrogen. If the liver be
present, this disintegration of blood-corpuscles causes a
greatly increased formation of bile-pigment, which is elimi-
nated with the bile, or partly reabsorbed by the lymphatics
from the biliary passages, giving rise to jaundice. If in a
goose the liver be shut out from the circulation or extirpated,
and arseniuretted hydrogen administered, not a trace of bile-
pigment is produced.

The cholesterin of the bile is sometimes looked upon as a
product of nerve-disintegration, since this substance is found
abundantly in the central nervous system ; but we have no
evidence for or against this view.

Bile is secreted at a very low pressure— 15 mm. Hg. If
the pressure in the bile-ducts rises above this point, as may
easily happen when the flow is obstructed in consequence of
inflammatory thickening of the mucous membrane, or by the
presence of a gall-stone, or even by a very viscid bile, the bile
is reabsorbed by the lymphatics and reaches the blood, and

346 PHYSIOLOGY

nearly all the tissues of the body are stained yellow by the
pigments, giving rise to jaundice. This pressure however is
higher than the pressure in the portal vein, which is only
about 10 mm. Hg ; for we must remember that the blood in
the portal vein has already passed through a system of capil-
laries, so that its pressure is extremely low. The fact that
the pressure in the bile-ducts may exceed that in the portal
vein shows that the secretion of the water of the bile is not
effected by a mere process of filtration.

THE MECHANISMS OF DIGESTION 347

Section 6
SUCCUS ENTEEICUS OE INTESTINAL JUICE

The secretion of the tubular glands (Lieberkiihn's follicles),
which beset the mucous membrane of the intestine, may be
obtained in a pure condition in the following way. An opening
is made into the abdomen of an animal, and a piece of the
small intestine, ten or twelve inches long, is separated from
the rest, its attachment to the mesentery with its blood-vessels
and nerves being left intact. The two ends of the remaining
piece of intestine are sutured together, so that the animal is
left with a continuous but shortened alimentary canal. One
end of the excised piece is closed by sutures, and the margins
of the other end sewn to the margins of the abdommal wound.
An intestinal fistula is thus produced, from which the juice
may be collected free from contamination by the other diges-
tive juices. Secretion is normally excited by the mechanical
stimulation of the food as it passes down the intestine, and
may be evoked in the isolated loop by the introduction of a
rubber balloon. The presence of pancreatic juice is said also
to act as a specific stimulus for the intestinal glands. The
amount of succus entericus to be obtained in either of these
ways varies very much according to the position in the
intestine of the isolated loop. Thus a large secretion is
obtained from an isolated loop of the upper part of the intes-
tine including the duodenum, and it is stated that in this
situation secretion may be excited by the intravenous injection
of secretin. If, however, a loop be made from the lower
end of the ileum, it is difficult to obtain even a few drops
of intestinal juice, whatever form of stimulation be employed.

Intestinal juice is a clear, limpid fluid, with a specific
gravity of 1010, containing a trace of protein, and salts,
of which sodium carbonate is the most abundant. In
consequence of the presence of this salt it has a strong
alkaline reaction.

Actions

On coagulable'proteins, fats, and starch, succus entericus
has no action. It contains however invert ferments, by the
agency of which cane-sugar is converted into dextrose and

348 PHYSIOLOGY

Isevulose, and maltose is converted into dextrose. Lactase,
which converts milk sugar into galactose and dextrose, is
often present, and is always found in animals on a milk diet.
The important ' ferment of ferments ' enterohinase, which
awakens the proteolytic activity of the pancreatic juice, has
already been mentioned. The alkaline reaction of the succus
is probably important in neutralising the free acids (lactic,
butyric, etc.) produced by the action of putrefactive micro-
organisms on the foodstuffs. Although intestinal juice has
no action on coagulable proteins, it contains a ferment,
erepsin, which converts the albumoses and peptones, produced
higher up in the gut, into the amino-acids and hexone bases
which are the final products of the action of trypsin on
proteins.

The following experiment is supposed to show the influence
of the intestinal nerves on the secretion. The abdomen being
opened, the small intestine is ligatured in four places, so as
to shut oft" three equal lengths of bowel ; all the nerves going
to the middle segment are divided and the abdomen closed.
At the end of two or three hours the wound is opened, and it
is found that the middle segment is distended with fluid,
whereas the other two segments, which have their nerves
intact, are comparatively empty. This secretion has been
regarded as analogous to the paralytic secretion of saliva,
which continues for some weeks after section of all the nerves
going to the submaxillary gland. We do not know however
how far this phenomenon is to be ascribed to vascular changes
taking place in the loop of intestine in consequence of the
section of its nerves.

THE MECHANISMS OF DIGESTION

349

Section 7
ABSOEPTION OF FOODSTUFFS

We must now consider the ways in which the foodstuffs,
that have been digested and rendered soluble in the ali-
mentary canal, pass into the circulation to be distributed to
all the cells of the body. There are two main paths of
absorption— the blood-vessels and lymphatics. The blood-
vessels form a dense capillary anastomosis immediately
under the epithelial layer covering the inner surface of the

Fig. 176.

Epithelium of

villus

Artery

Lieberkiilni's

follicle

Central lacteal

^^•m^^^^^^^MMMMM

— Mucosa

— Muscularis muc.

Lymphatic plexus

Circular muscle

Lymphatic plexus
Longitudinal muse.

Diagramniiitic section thiougli wall of small intestine to show
vascular and lymphatic arrangements of mucous membrane.
(From Bohm and Davidoff, after IMall.)

mucous membrane. In order to increase the absorbing sur-
face, the mucous membrane of the small intestine in man is
thrown into transverse folds — the valvules conniventes, which
are thickly covered with finger-like elevations or villi. The
body of a villus is made up of a reticular tissue composed of
branching cells, the meshes of which may contain leucocytes
of various forms. In the centre of the villus is a wide
lymphatic vessel, the central lacteal. The endothelial cells

350 PHYSIOLOGY

forming the wall of the lacteal are continuous with the
l)ranched cells of the reticular tissue, but there is no free com-
munication between the spaces of this tissue and the begin-
ning of the lymphatic. Below, the cavity of the lacteal is
continued into a plexus of lymphatics lying in the mucous
membrane, which communicates by vertical branches with
a large plexus lying in the submucosa. The intestinal surface
of the villus is covered with a single layer of columnar
epithelial cells, which have a hyaline border presentmg
delicate vertical striation, apparently due to the presence in
the border of a number of cilia-like processes. The capillary
network lies outside the lacteal immediately under the
epithelium. The blood-vessels pour their contents into the
radicles of the portal vein, which carry them thence to the
liver. The lymphatics in the submucosa join to form larger
trunks, which run between the two layers of the mesentery
to a collection of lymphatic glands at the back of the peri-
toneal cavity. The lymph, after flowing through these
glands, is collected into a large vessel — the receptaculum
chyli, from which it is carried in the thoracic duct to be
discharged into the blood-stream at the junction of the left
jugular and subclavian veins.

Absorption of Fats

During fasting the lymph contained in these vessels is
exactly similar to that contained in any other part of the
body. If a cannula be inserted in the thoracic duct of a
fasting dog, and the animal be given a meal rich in fat, it is
found that the amount of lymph flowing from the cannula
is the same as before, but the lymph has changed its appear-
ance, being now white like milk. On microscopic examina-
tion this milky appearance is found to be due to the presence
of small fatty globules similar to those in milk, and of a
number of very fine particles— much finer than any of the
globules met with in milk— which may exhibit Brownian
movement. These constitute the ' molecular basis ' of the
chyle. If the abdomen of the animal be opened, the course
of the lymphatics along the mesentery is evident from the
milky character of their contents. It is on account of this
milky appearance during digestion that the name of lacteal

THE MECHANISMS OF DIGESTION 351

has been given to the lymphatics of the ahmentary canal ;
and chyle is simply lymph with fatty globules, and molecular
basis.

Since the whole of the chyle is poured by the thoracic
duct into the blood, the plasma or serum of the latter,
obtained after a meal containing fat, is also found to present
a milky appearance, in consequence of the presence of fat
globules derived from the chyle. If however the thoracic
duct be ligatured, a fatty meal is not followed by any increase
in the amount of fat in the blood.

It is apparent then that the greater part of the fat is
absorbed by the chyle, and 60 per cent, of the absorbed fat
can be obtained from the chyle through a cannula placed in
the thoracic duct. Comparative analyses of portal and
carotid blood during digestion show that the amounts of fat
contained in the two are the same ; hence it is concluded
that no fat is absorbed through the intermediation of the
blood-vessels. It has not yet been found possible to trace
the mechanism of absorption of that portion of the fat which
does not enter the blood by way of the lacteals. It is
possible that it may be utilised or built up into more com-
plex compounds in the tissues of the intestinal mucous
membrane.

We must now inquire how the fat gets into the lacteals.
If sections be made of the villus during the digestion of fat,
and stained with osmic acid, the epithelial cells are seen to
be full of black fatty granules of various sizes (Fig. 177).
These granules are also to be observed in the spaces sur-
rounding the central lacteal.^ The lacteal itself is full of
lymph with fat-globules, but the latter are here much more
minute, and correspond to the molecular basis of the chyle.

We must conclude that the fat is taken up by the
epithelial cells covering the villus. But in what form '?
We have already seen that the effect of the pancreatic juice
on neutral fats, which form the great proportion of the fat
of food, is to split them up to a certain extent into free
fatty acid and glycerin. The rancid fat thus produced in an
alkaline medium at once forms an emulsion, and since the

' Many of the leucocytes also present black granules, but these are supposed
not to be of a fatty nature, since they are not dissolved on treating the section
with ether.

352

PHYSIOLOGY

chyle also contains fat in a finely divided condition, it was
thought that the digestion of fat essentially consisted in
a splitting up into particles fine enough to be taken up by
the epithelial cells. On examining sections of the villi
during fat-absorption, it will be seen however that the
striated border is always free from fat-globules, and that
the globules grow in size from the inner to the attached
border of the cell. Moreover by such an explanation it is
difficult to account for the extreme importance of bile for
the absorption of fat. It seems practically certain that there
is no fundamental difference between the absorption of fats

Fig. 177.

■••*V

• •• •

* 2« t

Columnar epithelium from small intestine of frog stained with
osmic acid to show fat-absorption. A, live hours after a
meal of olive oil ; B, three hours later. It should be noticed
that the fat globules first formed grow in size in the course
of digestion, pointing to a gradual deposition of fat on the
globules from solution in the protoplasm.

and that of carbohydrates and proteins, and that they are
all alike absorbed in a state of solution. If fatty acids are
administered to an animal they are absorbed, but appear
in the chyle as neutral fat, showing that a synthesis of
the fatty acid and glycerin has taken place on the passage of
the fatty acid from the intestine to the lacteal through the
epithelium. In the same way, soaps taken with the food
appear in the chyle as neutral fats, and in both cases the
assimilation is improved by the addition of the necessary
amount of glycerin. We may conclude that the formation of
an emulsion in the intestine is not the end of the digestive

THE MECHANISMS OF DIGESTION 353

process, but serves merely to bring a larger surface of the
fat in contact with the digestive juices. In the digestion
and absorption of fat there is a concerted action of the
pancreatic juice and the bile. The pancreatic juice splits
about 6 per cent, of the neutral fat into fatty acid and
glycerin. In the presence of excess of alkalies, the fatty
acid forms a soluble soap which, together with the glycerin,
is absorbed by the epithelial cells, and recombined in the
body of the cell into neutral fat. If, as is often the case
especially with a highly fatty diet, the reaction of the small
intestine be acid, the formation of soaps can no longer go on.
The fat-splitting action of the pancreatic juice however con-
tinues, and the fatty acids set free are dissolved by the bile
acid and taken up by the epithelial cells. Here the synthesis
of the neutral fat once more occurs, and the bile acid is
carried by the portal blood to the liver to be re-secreted with
the bile into the intestine, where it may aid the absorption of
a further amount of fat. As the free fatty acids and soaps
are absorbed, the pancreatic juice is able to split up a further
portion of the neutral fat, until the whole of the neutral fat
of the food has been absorbed by the epithelial cells of the
intestine in a state of solution as soaps or fatty acids.
It is partly on this account that, after extirpation of the
pancreas, fats are not absorbed even if administered to the
animal in the form of a fine emulsion containing neutral fat
suspended in a solution of soap. If however to this emulsion
chopped-up pancreas be added, a large proportion of the fat
is absorbed.

The epithelial cells extrude the fat-granules into the
spaces of the reticular tissue. Here a certain amount may
be taken up by the leucocytes and carried into the beginning
of the lacteal. The greater proportion however is probably
pressed forcibly through the wall of the central lacteal by the
contractions of the muscular tissue of the villus. A further
contraction of these fibres empties the lacteal into the
submucous plexus of lymphatics, where the presence of valves
prevents any reflux, so that, on relaxation of the muscle-
fibres, there is no hindrance to the further passage of fat and
lymph into the flaccid central lacteal. This is the so-called
pumping action of the villus.

23

354 PHYSIOLOGY

Absorption of Carbohydrates

The other constituents of the foodstuffs seem to be
absorbed chiefly, if not completely, by the blood-vessels.
Blood normally contains a small amount of dextrose (O'l to
0*2 per cent.), and the proportion of sugar in the lymph is
the same as in the blood. After a meal rich in carbo-
hydrates, the proportion of sugar in the chyle flowing from
the thoracic duct is the same as that in the blood from the
carotid artery ; but it is found that there is slightly more
sugar in the blood from the portal vein than in that from
the hepatic vein or carotid arter}'. It is inferred therefore
that the blood in the capillaries of the intestinal wall takes
up sugar in the form of dextrose and carries it to the liver.
Here the excess of sugar is taken up by the hepatic cells,
and converted by them into the colloid carbohydrate, gly-
cogen, which is deposited in the substance of the cell. In
this way the liver acts as a storehouse of carbohydrate
material, and prevents the sugar in a rich carbohydrate meal
from escaping into the general circulation. This function is
important, since it is found that if the amount of sugar in the
blood be raised above the normal, the excess is immediately
excreted by the kidney ; so that without such an economising
organ as the liver the greater part of a carbohydrate meal
would at once be wasted.

We have already seen (p. 336) that the end-product of the
action of the salivary and pancreatic ferments on starch
is a mixture of maltose and achroodextrin. In the blood
of the portal vein however, we find only dextrose ; and it
appears that the dextrin and maltose must undergo some
further change before reaching the blood. We know for
certain that the succus entericus contains a ferment which
can convert maltose into dextrose ; but it is possible also
that the epithelial cells lining the intestine are able to effect
a transformation of both dextrin and maltose into dextrose.
It must be remembered too that normal blood-plasma, serum,
and lymph contain a ferment which quickly converts boiled
starch, glycogen, dextrin, or maltose into dextrose. At any
rate under normal circumstances no dextrin or maltose is to
be found in the blood of the portal vein or in the chyle,
although these substances are absorbed from the intestine.

THE MECHANISMS OF DIGESTION 355

Absorption of Proteins

Proteins are for the most part converted into peptones
and albumoses before absorption. This absorption takes
place by means of the blood-vessels. Thus a large protein
meal is as readily absorbed in a dog whose thoracic duct is
ligatured as in a normal dog, A large protein meal always
gives rise to a marked increase in the amount of urea
excreted in the urine, and this increase is found also in a
dog whose thoracic duct has been ligatured, showing that
the protein has been absorbed and distributed through the
whole system.

If however we analyse the blood of the portal vein
during active protein digestion, not a trace of peptone is
found. Injection of even small quantities of albumoses or
peptone into the portal vein or any part of the blood-stream
gives rise at once to peptonuria, and the greater part of the
peptone injected reappears in the urine, from which it can
be collected. Thus it is impossible that the proteins can
reach the blood-stream in the form of peptone; and the
following experiments have been interpreted as showing that
peptone is regenerated into coagulable protein in its passage
through the epithelial cells of the alimentary canal.

A piece of the mucous membrane of the stomach during
active protein digestion is excised and divided into two
pieces. One piece (a) is thrown at once into boiling water,
and the other piece (b) is allowed to remain for three hours
in a warm moist chamber at 40-' C, and is then plunged
into boiling water. On analysing the two pieces a large
amount of peptone is found in a, whereas in b the merest
trace or none is present. During the stay in the warm
chamber, all the peptone in b has been converted into some-
thing else, probably coagulable protein. That this action
presumably depends on the vital activity of the epithelial
cells and not on unorganised ferments present in the cells, is
shown by the fact that plunging the membrane into water at
60° C. is as efficacious in stopping the action as when water
at 100° C. is used. At 60° C. all living cells in the body are
destroyed, but not all unorganised ferments.

The following experiment also points to a total disappear-
ance of the peptone during absorption : — A loop of a dog's

356 PHYSIOLOGY

intestine is excised, its contents washed out with a normal
saline fluid, one gramme of peptone placed in it, and the ends
ligatured. Dilute defibrinated blood is now passed for two or
three hours through the vessels supplying the loop in order
to keep it alive. At the end of this time, on cutting open the
loop, all the peptone is found to have disappeared, and on
analysis of the blood that has passed through the vessels
of the loop, no peptone can be found. It was therefore con-
cluded that peptone had been converted into a coagulable
protein in its passage through the absorbing epithelium.

More recent investigations by Leathes and others have,
however, tended to put a different interpretation on these
results. The mucous membrane of the whole alimentary canal
contains erepsin, and the disappearance of peptone can be
equally well explained on the assumption that it has been
entirely converted by this ferment into amino-acids and other
substances which no longer give the biuret reaction typical of
albumoses and peptones. It is true that so far observers have
failed to obtain any increase in the nitrogenous extractives of
the portal blood during digestion, but the circulation through
the vessels of the gut is so rapid that the whole of a large
protein meal might be absorbed in the form of these nitro-
genous extractives without giving such a rise in the amino-
nitrogen of the blood as to be detectable by our means of
analysis.

On the other hand, it is not necessary that the protein
should be all peptonised before being taken up by the
epithelial cells. It has been shown that protein, such as egg
albumen or acid albumen, may be absorbed by an isolated
loop of bowel or by the lower end of the large intestine, which
has been washed free from any trace of proteolytic ferment
that may have been carried down to it from the pancreatic
juice. Peptonisation however helps the work of the epithe-
lial cells, and materially hastens the process of absorption.
It is probable that a large proportion of the proteins of the
food may undergo complete disintegration into amino-acids
and bases, being absorbed in these forms into the blood, and
-built up again into proteins in the living cells of the tissues,
the extent to which any individual protein is broken down
during digestion being determined by the degree in which its
composition approximates to that of the normal proteins of
the digesting animal.

THE MECHANISMS OF DIGESTION

357

Absolution of Water and Salts

Owing to the simple character of the factors involved,
the study of the absorption of water and salt solutions from
the intestine is of considerable importance for the problem of
the mechanism of absorption generally, since it enables us to
determine whether the absorption is effected along purely
mechanical lines or whether the cells lining the intestine
take an active part in the process. On the latter hypothesis
we should regard the process as one of inverted secretion.
Whereas in glands the secretory epithelium takes up sub-
stances from the lymph and turns them out with more or less
modifications into the lumen of the alveoli, in the intestine
the epithelium would take up the food material and products
of digestion and excrete them in a more or less changed con-
dition on the other side into the lymph- and blood-spaces of
the villus.

Fk;. 178.

We may first consider the physical factors which would
influence the passage of water and dissolved substances
across the intestinal epithelium. In the case of two com-
partments A and B, separated by a permeable membrane c,
an interchange of material will go on so long as there is any
difference in the chemical composition on the two sides. If
the proportion of a dissolved substance such as sodium
chloride, be greater in a than in b, the movement of salt
from A to B will preponderate over that from b to a. If the
total number of dissolved molecules be greater in a than in b,
the osmotic pressure in a will be greater than the osmotic
pressure in b, and there will consequently be a flow of water
from B to A. In the case of substances of different diffusi-
bility, the less diffusible substance will exert at first more
osmotic pressure than the more diffusible, so that if equi-

358 PHYSIOLOGY

molecular solutions of sugar and sodium chloride be taken,
the fluid will move from the sodium chloride side on to the
sugar side at a greater rate than in the reverse direction ;
and the volume of the sugar-solution will increase at the
expense of the sodium chloride. It is evident that if the
membrane be partially or completely impermeable to certain
substances, these substances will have a greater effective
osmotic pressure and so be instrumental in determining an
absorption towards their side. Where however the fluids on
the two sides are identical, no property of the membrane will
effect a transference from one side to the other, nor can any
specific permeability cause the passage of a dissolved sub-
stance, so to speak, uphill, i.e. from a position of lower to
a position of higher partial tension. On investigating the
absorption of saline fluids from the intestines in the light of
these principles, we find that, although absorption is influ-
enced by the concentration and composition of the fluids
within the intestine, yet these physical factors are not the
only nor the chief determinants in the process, Init that the
living cells of the mucous membrane play an important part
in choosing and actively passing on certain constituents of
the food. If we take a solution of a salt, such as sodium
sulphate, the question seems at first sight a purely physical
one, a hypertonic ' solution being increased in amount, while
a hypotonic solution is concentrated by the absorption of
water, until its molecular concentration is the same as that
of the blood serum. If however we make use of the more
physiological solutions, such as dextrose or sodium chloride,
we find that these substances are absorbed rapidly from
weak or from strong solutions, the rate of absorption being
apparently very little influenced by the dift'usibility of the
substance in question. We can in fact represent absorption
as made up of two factors, the physical and the physiological.
Where they are in opposition, absorption goes on slowly
and represents work done on the fluid l)y the absorbing cells.
We may abolish this physiological factor by the addition of
such substances as sodium fluoride to the solutions, by which
means we poison the cells without apparently altering the

' A hypertonic solution is one that is more concentrated than normal fluids,
such as serum or normal NaCl solution. A hypotomc fluid is less concentrated
than a normal fluid.

THE MECHANISMS OF DIGESTION 359

consistence of the membrane. By a twisting of hypotheses,
it might be possible to exphxin even these facts without
recourse to a physiological factor, but it is impossible to
explain in this way the absorption of substances such as
serum or solutions of egg albumen, containing indiffusible
colloids in solution, and in the former case identical in all
respects with the serum circulating in the blood-vessels of
the villi.

We have already met so many examples of an activity of
the intestinal epithelium, such as the re-synthesis of fats, the
regeneration of peptone, and the passage by some means or
other of the regenerated coagulable protein into the blood-
vessels of the villi, that it is not strange to find the cell also
caring for the absorption of such necessary constituents of
the food as salts and sugars. Where the salts are of small
or no physiological importance, the cell in many cases
appears to have no power of physiological absorption, and
the salts exert their full physical influence, absorbing water
or retaining that by which they are dissolved, so that they
act as saline purges, e.g. sodium or magnesium sulphate.

The rate of absorption of water by the alimentary canal
increases from above downwards. No water or dilute saline
solutions appear to be absorbed by the stomach. If a
duodenal fistula be established, as much fluid will be dis-
charged by the fistula as is administered to the animal by the
mouth. In the small intestine, the process of absorption is
much more rapid in the ileum than in the jejunum. In
consequence however of the continual secretion of the succus
entericus, the intestinal contents reach the ileo-colic valve in
a fluid condition, and the excess of water is only absorbed in
the large intestine.

This difference in the absorbing power of different parts of
the gut has reference chiefly to water. Dissolved substances,
such as alcohol, dextrose, alkaloidal poisons, are absorbed with
extreme rapidity from the stomach as from all parts of the gut.

Water and salts are absorbed almost entirely by means
of the blood-vessels. If a cannula be placed in the thoracic
duct, little or no increase of the flow is obtained even during
the absorption of large quantities of salt solutions from the
intestine.

360 PHYSIOLOGY

Section 8

SUMMAKY OF THE CHANGES UNDEEGONE BY
THE FOOD IN THE ALIMENTAEY CANAL

In the mouth the food is broken up into small particles bj'
mastication, and moistened with alkaline saliva, in order to
fit it for deglutition. A small part of the starch is converted
into dextrin or maltose.

On reaching the stomach the action of the saliva may go
on for thirty to sixty minutes. At the end of this time
the secretion of gastric juice, excited by the presence of
food and of alkaline saliva in the stomach, is sufficiently
abundant to neutralise and render acid all the gastric
contents, and so stop the action of the ptyalin. Under the
action of the gastric juice the greater part of the protein is
dissolved, and converted into syntonin, albumoses, or pep-
tones. The connective tissues are also dissolved, setting free
the fat, which floats about in a free state. At the same time
some of the salts and sugar which have been swallowed,
and the peptones formed from the food, are being absorbed
by the gastric mucous membrane. For the first half-hour
after ingestion of a meal of solid food, the pylorus is firmly
closed. At the end of this time it relaxes at intervals to
allow the passage of the fluid parts of the gastric contents,
which are spoken of at this period as chyme. The passage
of food through the pylorus goes on for seven or eight hours
after the ingestion of food, and towards the end of this time
larger lumps of undigested material are allowed to pass on
into the duodenum.

As the acid chyme is squirted through the pylorus into
the duodenum, it comes into contact with the cells of the
mucous membrane, and in them causes a conversion of pro-
secretin into secretin. The latter is absorbed by the blood
stream and carried to the pancreas and liver, causing a flow
of pancreatic juice and an increased secretion of bile. The
strongly alkaline pancreatic juice neutralises the acid chyme.
So long as the duodenal contents are acid, the pylorus remains
closed, but opens as soon as sufficient pancreatic juice has

THE MECHANISMS OF DIGESTION 361

been secreted to neutralise the chyme that has ah'eady
passed through. When this happens the pylorus relaxes, a
fresh quantity of acid gastric contents is forced through,
more secretin is formed, and the pancreatic secretion is again
excited until the second amount of chyme is neutralised ; and
this self- steering regulation of the activities of the stomach,
pancreas, and intestines goes on until all the food has passed
through the pylorus. At the same time the pancreatic juice
poured into the gut evokes a secretion of succus entericus,
which supplies the enterokinase necessary for the activation
of the proteolytic ferment of the pancreatic juice.

In the duodenum the chyme comes in contact with the
bile, the flow of which is also quickened under the influ-
ence of the secretin which is being poured into the circu-
lation. This causes a precipitate in the chyme, consisting
of bile acids, syntonin, and albumoses. This precipitate is
dissolved later on by the further operation of the pancreatic
juice. Here the remaining digestive processes take place ;
the undigested proteins are dissolved, and the acid albumen
and albumoses resulting from gastric digestion are converted
into peptone and partially into leucine, tyrosine, and similar
nitrogenous bodies. Starches are changed into maltose and
dextrin, and, under the further agency of the intestinal juice,
into dextrose. The fats are partially split up and emulsified.

Throughout the whole of the small intestine active
secretion and absorption are taking place, so that the amount
of water in the intestinal contents in the lower part of the
small intestine is about the same as in the upper part. The
contents of the lower part acquire a distinct faecal odour from
the indol and skatol produced by the action of putrefactive
bacteria on the tryjitophane contained in the proteins of the
food. In the large intestine the processes of absorption
predominate over those of secretion ; hence that part of the
intestinal contents which has not been absorbed becomes less
and less watery, and acquires the character of faeces, in which
form it is periodically expelled from the body.

The fteces consist mainly of the indigestible residue of
the food, or of substances which have been taken in too large
quantities to be digested, and contain —

(rt) Cellulose, woody fibre, elastic tissue, keratin, and
remains of muscle-fibres, starch-grains, and fat.

362 PHYSIOLOGY

They also contain —

{h) The unabsorl)able part of the digestive juices, such as
mucin, altered cholalic acid {dijslysi)!), bile-pigments, clioles-
terin.

(c) Indol and skatol, various forms of bacteria, and disinte-
grated epithelial cells from the intestinal mucous membrane.

(d) Certain products of excretion of the intestinal mucous
membrane. Many metallic poisons {e.g. iron, mercury) are
excreted into the cavity of the intestine and leave the body in
the ffeces as sulphides of the metals.

THE MECHANISMS OF DIGESTION 36B

Section 9

MUSCULAE MECHANISMS OF DIGESTION

Mastication

By movements of the lower against the upper jaw, the
food is crushed ])etween the teeth and reduced to a finely
subdivided condition to fit it for the action of the various
digestive fluids. The lumps of food are continually pushed
between the teeth by movements of the tongue, cheek, and
lips. The whole act is voluntary, although it is associated
with and rendered easier by the saliva which is poured out
into the mouth at the same time, and the secretion of which
is excited reflexly.

The nerves supplying the muscles engaged in mastication
are the fifth nerve (to jaw muscles), facial, and hypoglossal.

Deglutition

When the food is sufficiently subdivided, it is gathered
by movements of the tongue against the hard palate into
a bolus which rests on the dorsal surface of the tongue,
whence it is propelled through the fauces into the oeso-
phagus.

The movements of deglutition may be divided into three
stages.

In the first stage the bolus is carried by the tongue
through the isthmus faucium. This act is voluntary. As
soon as the bolus has passed the isthmus, it is in a region
common to the food and respiratory processes.

Here, by a series of rapid reflex movements, constituting
the second stage, it is sent on into the beginning of the
cesophagus. The movements are as follows : — The levator
palati draws the soft palate upwards and l)aekwards, and this
with the contracted palato-pharyngei entirel}' closes the nasal
cavities. At the same time the intrinsic muscles of the
larynx contract, closing the rima glottidis by approximating
the vocal cords while the entire larynx is drawn up behind
the hyoid bone by the thvro-hyoid muscle, and the superior

364

PHYSIOLOGY

opening of the larynx is closed by the approximation of the
arytenoid cartilages to the l)ase of the tongue and the epi-
glottis. Then by the contraction of stylo-pharyngei and
palato-pharyngei the upper part of the pharynx is drawn like
a glove on a finger over the bolus of food, which is grasped by

Fm. 179.

Dissection to show muscles employed in^deglutition. b, styloid
process, from which arise 1, the styloglossus, 2, the stylohyoid,
3, the stylo-pharyngeus muscles ; c, section of lower jaw ; d, hyoid
bone ; e, thyroid cartilage ; g, isthmus of thyroid gland ; 4, cut
edge of mylohyoid muscle ; 5, 6, 7, 8, muscles of tongue ; 9, 10, 11,
supei'ior, middle, and inferior constrictors of pharynx ; 12, oeso-
phagus. (Allen Thomson.)

the superior constrictor, and passed on from this to the middle
and inferior constrictors of the pharynx.

The third or oesophageal stage is slow and entirely
involuntary. The bolus is forced down the oesophagus by
a peristaltic wave of contraction passing down the muscular
walls of this viscus.

The propagation of this contraction from one segment of

THE MECHANISMS OF DIGESTION 365

the cesophagus to the next is a reflex act. Section of the
vagus branches to the oesophagus arrests the wave, although
it is not checked by section of the cesophagus itself. A
peristaltic contraction is not necessary in most cases to
secure the carrying of food to the stomach. If a series of
acts of deglutition be made at intervals of a second, no
peristaltic wave of contraction takes place till after the last
mouthful has been swallowed. It seems that each act of
deglutition inhibits the third stage of the preceding one,
so that the food slides easily through a relaxed a-sophagus.

The cardiac end of the stomach is normally contracted,
but relaxes in the last stage of deglutition.

Nervous Mechanism of Deglutition

Deglutition is a complex reflex act, which is started by
impulses from the mucous membrane of the fauces or upper
part of the larynx. These travel up to the medulla through
branches of the fifth nerve and the su]ierior laryngeal branches
of the vagus. A movement of deglutition may often be
excited by stimulation of the central end of the superior
laryngeal nerve.

Stimulation of the central end of the giosso-pharyngeal
nerve checks any movements of deglutition that are in progress
and may excite vomiting.

The efferent channels are the hypoglossal nerve (to the
tongue), the fifth (to the mylo-hyoid), the giosso-pharyngeal,
vagus, and spinal accessory (to the muscles of the soft palate,
pharynx, and oesophagus). The vagus carries both motor and
inhibitory fibres for the lower part of the ctsophagus and
the cardiac sphincter of the stomach. Stimulation of the
peripheral end of the vagus in the normal animal causes
tonic contraction of the whole cesophagus. If however curare
and atropine be given, excitation of the vagus generally
inhibits the cardiac sphincter, so allowing of a free flow of
fluid from cesophagus to stomach.

Movements of the Stomacli

The stomach, which serves at once as a digestive organ
and as a reservoir which allows only small amounts of the
food at a time to pass into the intestines, is divided into

366

PHYSIOLOGY

cardiac and pyloric portions. Its muscular coat consists of
three layers, an outer longitudinal, a middle circular, and an
internal oblique layer, the first being continuous with the
longitudinal fibres, and the two latter with the circular fibres
of the oesophagus. About the middle of the pyloric half the
circular fibres are slightly thickened to form the ' transverse

Fig. 180.

Shadow sketches of the outlines of the stomach of a cat, immediately
after a meal (11.0), at various intervals afterwards (12.0, 2.0,
3.30, 4.30) ; c, situation of oesophageal opening ; y2, ' transverse
band;' ivx, junction of cardiac and pyloric portions. (W. B.
Cannon.)

band,' and at the pyloric orifice there is a very pronounced
thickening of the same fibres, forming the strong pyloric
sphincter. The movements of the stomach in the normal
animal have been studied by Cannon, by the administration
of subnitrate of bismuth with the food (bread and milk). On
examining the animal under the Eontgen rays, the opaque

THE MECHANISMS OF DIGESTION 367

bismuth salt caused a shadow of the outlines of the stomach
on the platino-cyanide screen. Figures obtained in this way
are shown in Fig. 180. Within five minutes after the end of
a meal slight constrictions appear near the middle of the
stomach and travel slowly towards the i)yloric end. The con-
tractions succeed one another at intervals of ten seconds, so
that the pyloric half is occupied with two or three such waves.
Ten or fifteen minutes after the first constriction has
appeared, the arrival of a wave at the pylorus is attended by
a relaxation of the pyloric sphincter and a squirting of some
of the contents into the duodenum. After this time the
pylorus opens at regular intervals to allow some of the gastric
contents to pass. The relaxation of the sphincter is at once
inhibited by the arrival of any solid or indigestible particle in
the region of the pylorus.

During this time, although free from distinct waves of
contraction, the cardiac part of the stomach has not been
idle. As the pyloric half empties itself into the duodenum,
the cardiac half contracts steadily on its contents, so com-
pelling ever fresh portions of food to enter the pyloric mill.
At the end of digestion the cardiac part is contracted to the
shape of a tube (Fig. 180, 4.30). The period elapsing from
the taking of food to the complete emptying of the stomach
may vary, according to the meal taken, from four to sixteen
hours.

Nervous Mechanism of the Stomach Movements

The manner in which these co-ordinated muscular con-
tractions are mitiated and carried out is quite unknown.
Since somewhat similar movements have been observed in
the excised stomach, it has been supposed that they are due
to a local nervous mechanism ; but whether this mechanism
is situated in the plexus of Auerbach between the muscular
coats, or m the microscopic ganglia which are found at
various places under the serous coat, is quite unknown.

From the central nervous system the stomach receives
fibres by two ways, viz. from the vagi and from the splanchnic
nerves. It is generally stated that the effect of the vagus is
to increase, and that of the splanchnic to diminish the stomach
movements. It is certain however that the vagi may act

368

PHYSIOLOGY

either as motor or inhibitory nerves to the walls of the
stomach as well as to the cardiac and pyloric sphincters.

Fig. 181.

LSyCk

G.SpW

LSp.N

Distribution of the vagus in the abdomen of the dog (M. H. Naylor).
R.V., L.V. Hight and left vagi. The right vagus runs behind
the oesophagus (Oe) and stomach {St), and in those places is
represented by a discontinuous line. Cb. Connecting branch be-
tween right and left vagi. P. Pancreas. Dd. Duodenum. F.D.J.
Flexura duodeno-jejunalis. I, I, 1, Intestine. L. Liver. K.
Kidney. A. Suprarenal capsule. E.G., L.G. Eight and left crura
of diaphragm. L.Sy.Ch. Left sympathetic chain. 12 D, 13 D.
Twelfth and thirteenth dorsal ganglia. 3 //. Third lumbar gan-
glion. G.Sp.N., L.Si^N. Great and small splanchnic nerves. S.G.
Left semilunai and superior mesenteric ganglia. D.A. Dorsal
aorta.

The most usual effect of stimulating the vagus, especially after
atropine, is contraction of the j)ylorus with relaxation of the
cardiac sphincter ; but in other cases there may be an equally

THE MFX'HANISMS OF DIGESTION 369

definite contraction of the cardiac sphincter, or an equally
definite relaxation of the pyloric sphincter. It is doubtful
whether in the higher animals the splanchnics have any
direct influence on the muscular wall of the stomach.

Vomiting

Vomiting is a reflex act which lies on the borderland
between physiological and pathological processes. It is at
any rate the normal reaction of the stomach to an irritant.
The act of vomiting is generally preceded by a feeling of
nausea, copious salivation, and retching. Retching is a
violent inspiration while the glottis is kept firmly closed, so
that air is drawn into the oesophagus, and distends it. This
stage is followed by contraction of the fibres radiating from
the cardiac end of the oesophagus, which opens and allows
gas to escape. The head being bent forward and the mouth
widely opened, so as to straighten the oesophagus as much
as possible, and the glottis kept closed, a forcible contraction
of the abdominal muscles occurs, attended by contraction of
the muscular wall of the stomach itself, which forces out its
contents.

Vomiting can be accomplished by contraction of the
stomach alone, or of the abdominal muscles alone ; for it
may be excited in an animal by injection of apomorphine even
after its stomach has been replaced by a bladder, or its
abdominal muscles and diaphragm paralysed by section of
the intercostal and phrenic nerves. Vomiting may be ex-
cited reflexly by irritation of the palate, fauces, stomach,
peritoneum, or indeed of any abdominal organ. It may also
be excited from the brain, in consequence of emotions or evil
smells. The co-ordination of the movements of vomiting is
dependent on a centre in the medulla — ' vomiting centre ' —
not far from the respiratory centre. The various emetics
may cause vomiting, either reflexly by irritation of the
stomach (mustard, salt water, zinc sulphate), or directly by
their action on the centre, e.g. apomorphine.

24

370 PHYSIOLOGY

Movements of the Small Intestine

The muscular wall of the small intestine is composed of
two continuous layers of longitudinal unstriated fibres ex-
ternally and circular fibres internally. Between the two
layers we find a peculiar nerve-plexus, ' the plexus of Auer-
bach,' composed of crossing strands of non-medullated nerve-
fibres with collections of ganglion cells at their nodal points.
Fine fibres given off from this plexus ramify among the
muscle-cells on each side. A finer plexus, the plexus of
Meissner, lies in the submucosa and sends nerves up into
the villi to supply the muscles of the muscularis mucosae and
the glandular epithelium.

On examining the small intestines in a warm saline bath,
after division of all nerves connecting them with the central
nervous system, they are seen to be in a state of continual
movement. The movements are of two kinds. In the first
place, all the coils of intestine are in a condition of swaying
motion, the movement from side to side being caused by slight
waves of constriction affecting both coats simultaneously and
travelling rapidly down the intestine at the rate of 2 to 5 cm.
per second. They recur at regular intervals of five or six
seconds, so that if a rubber balloon be placed in the intestine
and connected with a recording tambour, we get a tracing
as regular as that of a beating heart. These movements
are apparently myogenic, i.e. they are due to an inherent
rhythmicity of the muscle-fibres themselves and are propa-
gated down the intestine from one muscle-fibre to another.
They are increased in amplitude by local distension and in
frequency by rise of temperature. They are incompetent to
push a mass of food onwards ; their chief use seems to be to
effect a continuous movement and mixing of the intestinal
contents. In animals which have been fed with food con-
taining bismuth subnitrate, these contractions may be seen
under the Eontgen rays to cause the intestinal contents to
break up into segments, which fuse again to be broken up
by fresh constrictions. The movements are therefore often
called the ' segmenting movements.'

In strong contrast to these segmenting contractions are the
true peristaltic waves. Where not present spontaneously in
the exposed intestine, they may be easily evoked by intro-

THK MECHANISMS OF DIGESTION 371

ducing a bolus of cotton wool and vaseline into the gut. The
introduction of the bolus is at once followed by a twofold
effect. Immediately above the bolus, a strong ring of con-

FiG. 182.

Passage of bolus. Contractions of longitudinal coat (enteiograph).
The bolus (of soap and cotton wool) was inserted into the intes-
tine four inches above the recorded spot at a. The figures below
the tracing indicate the distance of the middle of the bolus from
the recording levers. As the bolus arrived two inches above the
levers there is cessation of the rhythmic contractions and inhibi-
tion of the tone of the muscle. This is followed, as the bolus is
forced past, by a strong contraction in the rear of the bolus.

striction is produced, and this travels slowly down the
intestine, driving the bolus before it. The rate of pro-

FiG. iH'd.

Intestinal contractions (balloon method). In this dog all the abdominal
ganglia had been excised, and botli vagi cut. Showing propagated
effects of mechanical stimulation above and below the balloon.
(1) pinch above, (2) pinch below, (.3) pinch below balloon.

gress of the wave is very variable and may be as little as a
centimetre in a minute. The passage of the bolus downwards
is rendered possible by an inhibition of all the spontaneous

372 PHYSIOLOGY

contractions of the intestinal wall for some distance below
the bolus, so that the advancing wave drives the bolus always
into a relaxed portion of the gut. A peristaltic wave there-
fore is a co-ordinated act involving two factors, an excitation
above and an inhibition below the excited spot. This two-
fold effect of local excitation can be easily demonstrated by
pinching the intestine above and below a balloon connected
with a tambour. A pinch above causes instant relaxation
of the gut at the balloon, whereas stimulation just below
causes increased tone and increased rhythmic contraction
(Fig. 183).

These peristaltic contractions, as well as the double re-
action to local stimulus, can be abolished by painting the
intestine with cocain or by injection of nicotine. Under these
circumstances the rhythmic swaying movements continue as
actively as before, but the intestine is powerless to move on
a bolus or mass of food. We must therefore regard them
as co-ordinated reflexes carried out by the local nervous
mechanism — the only example known so far of a true co-
ordinated reflex dependent entirely on peripheral nervous
structures.

Fig. 184.1

Excitation of both splanchnic nerves. Balloon method.
Intestine returned to abdomen.

Innervation of Small Intestine

The small intestine receives fibres (1) from the greater and
smaller splanchnic nerves which run through the semilunar
and superior mesenteric ganglia and arrive at their destination

THE :\[ECHANISMR OF DIGESTION

873

along the mesenteric arteries, and (2) from the continuation
of the right vagus. The hitter however contains fibres from
both vagi in the neck. The sphmchnic nerves convey purely
inhibitory impulses (Fig. 184), the inhibition being independent
of the simultaneous effect on the blood-vessels of the intestines.
Both longitudinal and circular fibres are involved in the inhi-
bition. Any painful stimulation of a sensory nerve, especially

Effect of stiinuliitiou of riirht va^us un intcotiual coutraction>

in the abdomen, excites a retiex inhibition, so that it is
necessary to cut all the splanchnic fibres if we wish to study
by operation the normal activities of the mtestine.

The vagus is a motor nerve to the intestme. Stimulation
of the vagus after the administration of atropine (to paralyse
the cardio-inhibitory fibres) gives, after a prolonged latent
period, increased amplitude of the rhythmic contractions
accompanied by augmentation of tone (Fig. 185).

In the dog there is a preliminary temporary inhibition,
but this inhibition is possibly determined by an immediate
motor effect on the stomach or duodenum, since it is absent
in such animals as the rabbit, where a descending inhibition
as the result of local stimulation is also absent or little
marked.

B74 PHYSIOLOGY

Movements of Large Intestine

Just as at the upper end of the Hhmentary canal there is
a gradual transition from the co-ordinated cerebro-spinal
reflex of deglutition to the local automatic movements of the
stomach, so in the large intestine we find a gradual transition
in the opposite direction, the activity of the gut becoming less
automatic and more dependent on its extrinsic innervation as
we proceed from ileo-colic valve to anus. The muscular wall
consists, as in the small intestine, of two coats, the outer
longitudinal fibres however being especially condensed in
man and some animals to form three bands of muscular fibre.
The colon separated from its nervous connections shows slow
rhythmic contractions, much more irregular and less frequent
than those of the small intestine. A peristaltic wave may
often be produced in the upper part of the colon or be trans-
mitted onwards from the ileum, but in nearly all cases dies
away before arriving at the sigmoid flexure.

In the upper part of the large intestine in many animals
we find peristaltic movements alternating with antiperistaltic
movements, so that the onward movement of the intestinal
contents is cut short by a reverse contraction which drives
them up against the ileo-caecal valve. The to and fro move-
ment of the intestinal contents seems specially adapted for
enabling the organism to extract the last traces of nutriment
from the contents of the gut before these are passed on as
faeces into the lower bowel.

Innervation of Large Infesfiiie

The colon receives fibres from two sources — from the
lower dorsal and upper lumbar nerves, and from the second
and third sacral nerves. The upper set of nerves pass by the
rami communicantes into the sympathetic chain, thence into
the inferior mesenteric ganglion, where many of them make
connections with the ner^'e-cells. From the ganglion they
pass as non-medullated nerve-fibres along the branches of
the inferior mesenteric artery in the walls of the gut.
(Fig. 30G.) The sacral fibres pass in the pelvic visceral
nerves or nervi erigentes to the hypogastric plexus, whence
branches are given off, which run up in the walls of the colon.

THE MECHANISMS OF DIGESTION 375

The action of these two sets of nerves is exactly analogous to
that of the nerves supplying the small intestine, the part of
the vagus being taken by the pelvic visceral nerve. The
branches of the inferior mesenteric ganglia are purely inhi-
bitory to both longitudinal and circular coats, whereas the
sacral nerves cause a strong contraction of both coats, which
may in some cases take the form of a descending peristaltic
wave, but is in all cases accompanied by a strong contraction
of the thickened collection of longitudinal fibres forming
the recto-coccygeal muscle. This contraction is in the dog
often preceded by a preliminary inhibition analogous to that
produced in the small intestine by the vagus.

A well-marked band of circular muscles forms a sphincter at the entry of
ileum into colon. It is interesting to note that excitation of the splanchnics,
which inhibits all the rest of the gut, causes a strong contraction of the ileo-
colic sphincter.

Defaecation

The residue of the undigested food and other matters
forming the faeces are driven on by the peristaltic contractions
of the upper part of the large intestine, until they reach
the sigmoid flexure. The mass of faeces accumulates in the
sigmoid flexure, and is added to after each meal.

The anus is closed by two distinct muscles — the external
sphincter, a thin sheet of striated muscle ; and the internal
sphincter, a thick ring of unstriated muscle surrounding the
last three inches of the rectum, and about half an inch thick.
The internal sphincter is normally in a condition of tonic
contraction. This contraction however is not usually needed
to keep back the faeces, since any that have escaped past the
sigmoid flexure are retained in the upper part of the rectum
by a transverse fold of mucous membrane. They are also
kept back by the acute angle that the last part of the rectum
makes wdth the preceding part, and by the contractions of the
perinaeal muscles which maintain this curvature and empty
the lower part of the bowel.

Defaecation is normally started by a voluntary act, although
it may take place involuntarily, as is shown by the fact that
it occurs in a dog whose spinal cord has been divided in the
dorsal region.

376 PHYSIOLOGY

The steps of normal defsecation are as follows : — The
glottis being closed, a forcible expiratory effort of the abdo-
minal muscles is made. The perinceal muscles being relaxed
at the same time, the lower part of the rectum is straightened,
and a portion of the contents of the sigmoid flexure is forced
down into the lower part of the rectum. The presence of a
foreign body in the lower part of the rectum irritates the
mucous membrane, and excites reflexly the rest of the act.
Strong peristaltic contractions take place along the whole of
the descending colon (sigmoid flexure and rectum), while both
sphincters are relaxed, thus forcing out the contents of the
bowel. The recto-coccygeal muscle contracts forcibly at the
same time, ])ulling down and straightening the lowest part of
the bowel and causing some eversion of the mucous membrane.
The last section of the rectum at the close of the act is emptied
by a forcible contraction of the levator ani and the other
perinfieal muscles, and this contraction also serves to restore
the everted mucous membrane.

The carrying out of this reflex act is dependent on the
integrity of a certain part of the lumbar spinal cord. If this
' centre ' be destroyed, the tonic contraction of the sphincter
muscles disappears. This centre may be either excited to
increased action, or be inhibited by peripheral stimulation of
various nerves, or by emotion, such as fear. Application of
warmth to the region of the anus causes reflex relaxation
of the sphincter ; application of cold increases its tonic con-
traction.

377

CHAPTER IX

RESPIRATION

Section 1
THE EESPIRATOEY MOVEMENTS

The processes of external respiration, namely, the taking up
of oxygen and the giving off of carbon dioxide— the product
of the union of the oxygen with the carbon of the foodstuffs —
are effected in the lungs, which are built up in the following
way. The trachea or windpipe, a wide tube about 4i inches
long, divides below into two main branches— iro?ic/ri ;
and these subdivide again and again, becoming gradually
smaller. The terminal ramifications or hroncliioles open into
rather wider parts — the infundihula, the walls of which are
beset with a number of minute cavities, the alveoli. The
larger tubes are kept patent by rings or plates of cartilage in
their walls. The smaller tubes have no cartilage, their walls
being composed of fibrous and elastic tissue and a coating of
unstriated muscular fibres, which are able by their contraction
to occlude the passage. The whole system of tubes is lined
with a layer of epithelium — ciliated columnar in the trachea,
bronchi, and bronchioles, and cubical over the parts of the
infundibulum not occupied by air-cells.

The alveoli are the special respiratory parts of the lung.
Their walls are composed of connective tissue containing a
large number of elastic fibres, and are covered internally by
a single layer of extremely thin large flattened cells. The
alveoli are closely packed together, so that in a section of
the lung an alveolus is seen to be in contact with others on
all sides. Immediately below the squamous epithelium ramify
blood -capillaries derived from the pulmonary artery. These
form a close network, and the blood in them is in close
proximity to air on all sides, being separated from the air in

378

PHYSIOLOGY

the alveoli only by the thin endothelial cells of the capillary
wall and the flattened cells lining the alveoli.

The lungs in their development grow out from the front
part of the alimentary canal into the front part of the body-
cavity on each side — the pleural cavity. The surrounding
body-walls become strengthened by the formation of the ribs,
so that the lungs are suspended in a bony cage-work, the
thorax. Their outer surface is covered with a special
membrane, the pleura, which is reflected on to the wall of
the thorax from the roots of the lungs, and completely lines
the cavity in which they lie. The surface of the pleura

Fig. 186.

Diagrammatic representation of the structure of the lungs. Tlie
trachea branches into two bronchi, which subdivide again and
again before ending in the infundibula (from Yeo).

facing the pleural cavity is lined with a continuous layer of
flattened endothelial cells, and is kept constantly moist by
the secretion of lymph into the cavity. Thus, being attached
to the thorax only where the bronchi and great vessels
enter, the lungs are able to glide easily over the inner surface
of the thorax, with which under normal circumstances they
are in intimate contact.

A constant renewal of the air in the lungs is secured by
movements of the thorax, which constitute normal breathing.
With inspiration the cavity of the thorax is enlarged, and

RESPIRATION 379

the lungs swell up to fill the increased space. The capacity
of the air-passages of the lungs heing thus increased, air is
sucked in through the trachea. The movement of inspiration
is followed by that of expiration, which causes diminution of
the capacity of the thorax and expulsion of air.

The expiration follows immediately upon inspiration. At
the end of expiration there is normally a slight pause. The
number of respirations in the adult is about 17 or 18 a
minute. This is however much influenced by various con-
ditions of the body, and also by the age of the individual.
Thus a new-born child breathes about 44 times a minute, a
child of five about 26 times, a man of twenty-five about 16,
and of fifty about 18. The frequency is increased by any
muscular effort, so that even standing up increases the
number of respirations. These movements are much affected
hy psychical activity ; they are to a certain extent under
the control of the will, although, as we shall see later, they
can occur in an animal deprived of its brain, and we know
they are normally carried out without any special act of
volition. We can breathe fast or slow at pleasure, and can
even cease breathing for a time. It is impossible however
to prolong this respiratory standstill for more than a minute ;
the need of breathing becomes imperative, and against our
will we are forced to breathe.

With every inspiration the cavity of the thorax is enlarged
in all dimensions, from above downwards by the contraction
of the diaphragm, and in its transverse diameters by the
movements of the ribs.

The diaphragm is a sheet of muscle separating the cavity
of the chest from that of the abdomen. This sheet, which is
tendinous at the centre, is arched, the convex side protruding
up into the thorax, forming thus a dome-like boundary of
the peritoneal cavit3\ In expiration the lateral muscular
parts of the diaphragm lie in contact with the lower part of
the thoracic wall. During inspiration the muscle-fibres con-
tract and draw the central tendon downwards, so that
the lower border of the lungs descends (Fig. 188). The
enlargement of the lungs at the lower part of the thorax
is aided by the abduction of the floating ribs, produced by
the contraction of the quadratus lumborum and deep costal
muscles. In this contraction the diaphragm presses on the

380 PHYSIOLOGY

contents of the abdomen, so that the abdomen swells up with
each inspiratory movement.

In forced inspiration the descent of tlie tendinous part of the diaphriigni
may also involve the heart and inferior vena cava.

The enlargement in the other diameters is effected by an
elevation of the ribs. Each pair of corresponding ribs, which
are articulated behind with the spinal column and in front
with the sternum, forms a ring directed obliquely from
behind downwards and forwards. With each inspiratory
movement the ribs are raised, the obliquity becomes less,
and the horizontal distance between sternum and spinal

Fig. 187.

Diagi'am showing movements of diaphragm in respiration, i i,
inspiratory position ; e e, expiratory position. (Yeo.)

column is therefore increased. Moreover the ribs from the
first to the seventh increase in length from above downwards,
so that when they are raised, the sixth rib, for instance,
occupies the situation previously taken by the fifth, and the
transverse diameters of the thorax at this height are in-
creased. With each inspiration there is a rotation of the
ribs. In the expiratory condition they are so situated that
their outer surfaces are directed not only outwards, but also
downwards. As they are raised by the inspiratory move-
ments, they rotate on an axis directed through the fore and
hind ends of the rib, so that their outer surfaces are turned
directly outwards. In this way a certain enlargement of the
thoracic cavity is produced. As the thorax is raised there is
alwavs some stretching of the rib cartilages.

EESPIRATION

381

111 expiration the processes are reversed, and the cavity of
the thorax is diminished in all three dimensions.

The movements of the thorax are effected by means of
muscles. Inspiration is performed by the following muscles :

The diaphragm, which is the most important, and almost
suffices alone to carry out quiet respiration.

The external intercostal muscles, which shorten and so
raise the ribs.

The levatores costarum and serratus posticus superior.

These muscles are the only ones normally engaged in
carrying out inspiration. When, in consequence of muscular
exertions or from any other cause, the inspiratory efforts

Fig. 188.

Four dorsal vertebras and their ribs to show attachments of respiratory
muscles. (A. Thomson.) 1 1, levatores costarum ; 2, external
intercostal ; 3, internal intercostal.

become more forcible, a large number of accessory muscles
are brought into play. These are —

The scaleni,

Sterno-mastoid,

Trapezius,

Pectoral muscles.

Rhomboids, and

The serratus anticus.

Normal expiration is chiefly effected passively. When the
inspiratory muscles cease to contract, the lungs, which were
stretched })y the previous inspiration, contract by virtue of
the elastic tissue they contain, and the thorax itself sinks by
its own weight, and by the elastic reaction of the stretched

382

PHYSIOLOGY

costal cartilages. Probably under normal circumstances the
internal intercostal muscles also contract with each expira-
tion.

Although the action of the intercostal muscles has been a subject of debate,
physiological experiments serve on the whole to confirm the view first put
forward by Bamberger and based on a consideration of the direction of the
fibres. The external intercostals pass from one rib to the next below down-
wards and forwards. Hence if a pair of ribs be isolated from the rest of the

Fig. 189.

chest-wall, leaving the vertebral and costal attachments intact, contraction of
these muscles will cause a rise of both ribs. This result will be evident from
a consideration of Fig. 189, where a i is a fibre of the external intercostal
muscles, passing from the rib u s to be attached to the rib v' s' at b. When
a b contracts, the tension it exerts on its two attachments can be resolved into
two components a c acting downwards and b d acting upwards, b d however
acts at the end of the long lever b v', whereas a c acts at the end of a short

Fig. 190.

lever a v. Hence the raising effect will overcome the depressing effect, and
both ribs will rise.

The fibres of the internal intercostals run in the opposite direction to the
external nuiscles, and from a consideration of Fig. 190 it is evident that their
effect will be to depress any pair of ribs, thus acting as expiratory muscles.

Owing to the fact that the costal cartilages make an angle with the bony
ribs, the fibres of prolongation of the internal intercostals, mtiscitli intcrcarti-
laginei, have the same relation to their attachments that the external inter-
costals have to the bony ribs. Their action therefore must be to raise the

KESPIRATION 383

cartilages and flatten out the angle between the cartilaginous and bony ribs, so
that they must act with the external intercostals as inspiratory muscles.

In forced expiration a large number of muscles may take
part — such as the serratus posticus inferior, and the muscles
forming the wall of the abdomen, i.e. the rectus, obliquus, and
transversus abdominis muscles.

As the lungs expand with each inspiration, their position
changes somewhat in relation to the thoracic wall. The
roots, the hinder borders, and the apices of the lungs remain
nearly stationary. The front parts move downwards and
inwards, so that their inner borders in front approach one
another. By percussing the chest, it may be easily made
out that the resonant area, corresponding to the parts where
the lungs are in contact with the thoracic walls, increases
with each inspiration, and diminishes with each expiration.

Even at the end of expiration the lungs are in a stretched
condition. This is shown by the fact that if in an animal
or in the corpse an opening be made into the pleural cavity,
air rushes into the opening and the lungs collapse, driving a
certain amount of air out through the trachea. Smce then
the lungs are always tending to collapse, it is evident that
they must exert a pull on the thoracic wall. This pull of
the lungs gives rise to a negative pressure in the pleural
cavity. If we connect a mercurial manometer with the
pleural cavity, we find this pull of the lungs amounts in the
corpse to 6 mm. of mercury. If the lungs are fully distended,
as after full inspiration, the elastic forces are more brought
into play, and the negative pressure in the pleura may
amount to 30 mm. Since the lungs are always tending to
collapse, respiration becomes impossible directly free open-
ings are made into the pleural cavities on both sides. With
each inspiratory movement air rushes in through these
openings, so that the thoracic movements can no longer exert
any influence on the volume of the lungs. The negative
pressure in the thorax is diminished by any factor de-
creasing the elasticity of the lung-tissue. Thus in an old
man, where the elastic tissue is degenerated and the alveoli
are enlarged, giving rise to the condition known as emphy-
sema, the lungs may collapse only slightly or not at all on
opening the chest. The lungs do not collapse on making an
opening in the chest of a new-born mammal ; but this is

384 PHYSIOLOGY

owing to the fact that the hings completely fill the thorax
in the expiratory position, and it is only later that with the
growth of the ribs the thorax gets, so to speak, too large for
the lungs, which are therefore stretched to fill it.

The force exerted by the inspiratory muscles is nearly
all spent in overcoming the elastic resistance of the lungs
and costal cartilages. A free access of air is provided for
by contractions of certain accessory muscles of respiration.
With each inspiration the glottis is widened by abduction' of
the vocal cords. When the glottis is observed by means of
the laryngoscope, a rhythmical separation and approximation
of the vocal cords are observed, synchronous respectively
with inspiration and expiration. When inspiration is laboured,
the alse nasi are dilated by the action of the dilatator nasi.
This movement of the nostril, which is constant in many
animals, becomes very prominent in children suffering from
any respiratory trouble.

If a manometer be connected with one of the nostrils, so
as to register the pressure in the air-cavities, it is found that
there is a negative pressure of — 1 mm. Hg with inspira-
tion, and a positive pressure of 2 or 3 mm. with expiration.
With forced inspiration the negative pressure may amount
to —57 mm. Hg, and with forced expiration there may be a
positive pressure of + 87 mm.

Under no circumstances can we by forced expiration
empty the lungs of air. At the end of the most forcible
expiration, if the pleura were perforated, the lungs would
collapse and drive more air through the trachea. When
breathing quietly a man takes in and gives out at each breath
about 500 c.c. of air, measured dry and at 0° C. If measured
moist and at the temperature of the body, viz. 37° C, the
volume would be 604 c.c. This amount is known as the
tidal air. By means of a forcible inspiratory effort it is
possible to take in about 1,500 c.c. more {complemcntal air).
At the end of a normal expiration a forcible contraction of
the expiratory muscles will drive out about 1,500 c.c. more
{supplemental air). These three amounts together constitute
the ' vital capacity ' of an individual. This total may be
determined by means of the instrument known as the spiro-
meter, which is merely a small gas-meter with a gauge by
which the amount of air in it can be at once read off. The

EESPIKATION 385

person to be tested tills his lungs as full as possible, and then
expires to the utmost into the spirometer. The air left in
the Imigs after the most vigorous expiration {residual air)
amounts to about 2,000 c.c.

The residual air may be determined by letting a person expire to the
utmost extent and then connecting with his mouth or nose a bag of known
capacity filled with hydrogen. The subject of the experiment then inspires
and expires into the bag two or three times, ending in the same state of forced
expiration as he began. Any diminution of the total volume of gas in the bag
will represent the gas lost during the experiment by diffusion into the blood-
vessels. By analysis of the gaseous mixture in the bag, it is possible to
determine the amount of air in the lungs at the beginning of the experiment.
Supposing for example the bag held 4,000 c.c. hydrogen, after two respirations
the total volume is unaltered, but the gas is found to consist of 3,000 c.c.
hydrogen and 1,000 c.c. oxygen, nitrogen, and CO.^, i.e. pulmonary gases. Since
the gas in the lungs must have the same composition and 1,000 c.c. hydrogen
have disappeared from the bag, it is evident tbat the lungs will contain 1,000 c.c.
hydrogen and i-— , i.e. 330 c.c. pulmonary gases. Thus the total volume of
gas left in the lungs at the end of the forced expiration was 1,330 c.c, which is
the residual volume for the individual.

Of the 500 c.c. of tidal air taken in at each inspiration,
only a certain part reaches the alveoli, part being required
to fill the air-tubes, trachea, bronchi, and bronchioles which
lead to the air-cells. The volume of the air-tubes has been
reckoned to amount to 140 c.c, so that of the 500 c.c. about
360 c.c. reach the alveoli. For the same reason the expired
air represents the air from the alveoli (360 c.c.) diluted with
140 c.c. of air which has remained in the air-tubes and
undergone very little change, other than the elevation of
temperature and saturation with aqueous vapour. We have
therefore to allow for this air contained in the so-called
' dead space ' of the lungs when we seek to arrive at the
composition of alveolar air from an analysis of expired air.
We must remember however that the air in this dead space
is not absolutely wasted, since it is constantly midergoing
interchange by diffusion with the alveolar air, and thus
serves to carry some of the oxygen to and some of the CO^
away from the pulmonary alveoli, although never in contact
with the latter.

25

386 ■ PHYSIOLOGY

Section 2
CHEMISTEY OP EESPIEATION

The respiratory movements are but means to an end.
They enable the blood to take up oxygen and give off carbon
dioxide on its way through the lungs, so that the blood reaches
the tissue-elements prepared to supply them with oxygen and
to take up carbon dioxide, the product of their destructive
metabolism. We have now to study the conditions that
regulate gaseous interchange in the lungs and in the tissues.

As we should expect, analysis shows marked differences
in the constitution of inspired and expired air. Inspired
air — that is to say, ordinary atmospheric air — consists of
a mixture of oxygen and nitrogen, with a very small trace of
carbon dioxide gas. Its composition is —

Oxygen ..... 20-96 vols, per cent.

Nitrogen .... 79

Carbon dioxide . . . 0-04 vol. ,,

It also contains a variable amount of watery vapour, but is
very rarely saturated with it. Its temperature of course
varies with the season of the year.

The chief change that occurs in respired air is a decrease
of the oxygen, and a corresponding increase of carbon dioxide.
Its average composition in man is —

Oxygen .

. Ki-O vols, per cent.

Nitrogen .

. 79-6 „

Carbon dioxide

■ 4-4 „

It is moreover nearly saturated with watery vapour, which on
a cold day condenses in a cloud of steam with every expira-
tion. Its temperature, which is very slightly affected by that
of the external air, is a little below the normal body tempera-
ture (about 36° C). If the inspired air is above the body
temperature, the expired air is found to be cooled down to
the temperature of the body. If the inspired and expired air
be carefully measured in a dry condition at the same tempera-
ture, it will be found that the volume of expired air is about
5V less than that of the inspired. The conversion of oxygen
into carbon dioxide would not of course cause any change
in the volume of the gas ; for one molecule of oxygen (O.J

RESPIRATION 387

would, on combining with carbon, give rise to one molecule

of carbon dioxide (CO.,), which at the same temperature and

pressure would occupy exactly the same volume. But it

must be remembered that carbon is not the only element

which leaves the body in an oxidised condition. Fats, for

example, contain a number of unoxidised atoms of hydrogen,

which in the metabolic processes of the body are fully oxidised

to be excreted as water. A certain amount of oxygen too is

used up in the oxidation of the nitrogenous elements of food,

which are excreted chiefly as urea. Thus a certain amount

of oxygen is taken in which does not reappear as CO.^ in

expired air. Hence, although the total volume of nitrogen

expired is the same as that inspired, its percentage amount

is rather greater in expired than in inspired air. We should

expect to find this apparent loss of oxygen greater in carnivora,

v/hose food consists mainly of proteins and fats, than in

herbivora, which feed principally on carbohydrates. This

indeed is found to be the case.

^, . t!0, expired . .

The quotient q • • . i is known as the respiratory

quotient. From the precedmg remarks, it is evident that it
can never be greater than 1, if the observation be extended
over a fairly long period, and that it is less in carnivora
than in herbivora.

If an animal could live on a purely carbohydrate diet, its respiratory
quotient would be exactly 1, since the hydrogen and oxygen in the carbohydrate
molecule are in the exact proportion to form water and can therefore be dis-
regarded. Thus :

C«H,,0, + 6 0, := 6 CO, + 6 H,0.
(Dextrose)

The case is different with fats. If we assume an animal to be fed on pure
olein, the respiratory changes will be represented as follows :
C,H,{C,,H330,)3 + 80 0,, ^ 57 CO, + 52 H,0.

57
Here the respiratory quotient is - - — 0'71.

Egg albumen may be roughly represented as CiooHj^^N^^OjaS. The oxidation
would take place as follows :

C,„,Hi,oN,,033S + 1071 0, = 89 CO, + 5-1 H,0 + 13 CON,H^ + SO^.

(Urea)

89
Here the respiratory quotient is ^^r^^-z = 0-82.

In the case of the isolated frog's muscle, or of the whole
frog in an atmosphere of nitrogen, the respiratory quotient
may be very large. In warm-blooded animals however, the

388 PHYSIOLOGY

intake of oxygen must always run parallel to the output
of COg, and it is not found that moderate muscular activity
alters in any way the respiratory quotient. With very
severe exercise leading to dyspnoea, there may be a temporary
rise of the quotient, but such a condition cannot be regarded
as normal.

On the other hand very considerable alterations may take
place in the respiratory quotient, if the organism is, so to
speak, altering its invested capital, and converting a large
amount of carbohydrates into fat, or fat into carbohydrates.
This will be evident if we compare the formula for a fatty
acid with that of dextrose. Thus :

Thus to convert fat into carbohydrate, a large amount of

oxygen must be taken in, which will not appear at all in the

CO
excreta. The respiratory quotient p. - will be therefore very

small, and in hibernating animals, where this change occurs
to a large extent, it may not exceed 0*2 or 0-3; and the animal
may even gain weight by the absorption of oxygen. On the
other hand when carbohydrates are being largely converted
into and stored up as fat, a large amount of oxygen will be
available for the production of CO^ from the simple decom-

CO

position of the carbohydrate. In such cases ? will be

O2

large, and may amount to as much as 1-5.

As was shown on p. 385, only a certain percentage of the
500 c.c. of tidal air reaches the alveoli, 100 to 140 c.c. being
required to fill the trachea and bronchial tubes. Hence the
alveolar air must contain more carbon dioxide and less oxygen
than the tracheal air ; and it is found that, if we take the air
from the alveoli instead of that expired through the mouth
or nose, the differences between it and the inspired air are
much more pronounced.

A sample of alveolar air may be obtained for analysis in the following way
(Haldane) : A piece of indiarubber tubing is taken of about 1 inch diameter
and 4 feet long. Into one end (Fig. 190a) is fitted a mouthpiece, the other
being left open or connected with a spirometer. About 2 inches from the
mouthpiece is fixed a gas sampling-bulb, which is provided with three-way taps
at the upper and lower ends. Before an experiment the bulb is filled with
mercury, if the lower end is open, or else it is completely exhausted. The sub-
ject of the experiment, after breathing normally a few times through the tube,

RESPIRATION 889

at the end of a normal inspiration, expires quickly and deeply and closes the
mouthpiece with his tongue. The tap of the sampling-bulb is then turned,
and the air last expelled from the lungs (which is therefore pure alveolar air)
rushes into the bulb. The top of the bulb is then turned ofT, and the gas may

Fig. 190a.

Aifo(/r//-/=/£C£.

S/IMPL/N6 TUBS.

be removed for analysis. A similar sample is then taken, in which the subject
expires deeply at the end of a normal expiration. This sample will, of course,
contain more CO,^ and less O., than that obtained at the end of inspiration. The
mean of the two samples is taken as the average composition of alveolar air.

The difference between the composition of expired air
and alveolar air is determined l)y the dilution of the alveolar
air with that contained in the dead space. Hence with
shallow breathing there will be a large difference, but this
will decrease with increased depth of respiration. Thus if
the alveolar air contained 6 per cent. CO^ and the dead space
amounted to 150 c.c, the expired air would only contain
3 per cent. CO^ when the person was taking in only 300 c.c.
at each respiration. If however he was breathing slowly
and deeply so as to raise the tidal air to 1,500 c.c , only one-
tenth of this would be represented by the dead space, and the
expired air would contam nine-tenths as much CO^, as the
alveolar air, i.e, 5'4 per cent.

Bespiratory Changes in the Blood

From 100 volumes of either venous or arterial blood we
can, by means of the mercurial pump, remove about sixty
volumes of gas.

A great variety of pumps has been devised for this purpose. One of the
simplest of these (Hill's blood-pump) is shown in Fig. 191, and will serve to
illustrate the principle on which all the other pumps are constructed. 'In
extracting the gases of the blood by means of this pump, a blood receiver is
affixed to the end of the tube e, and the receiver is elevated into the position
indicated by the dotted outline. The receiver (b) is then put in connection with
the tube (e) by means of the three-way tap (d), the reservoir (a) is raised above
the pump, and the whole system is filled with mercury to the top of the blood
receiver (f). The screw clip on the rubber tube, at the upper end of f, is then
closed, and the reservoir (a) lowered until the blood receiver is exhausted, except
for 2 or 3 c.c. of mercury, which are purposely left within. The screw clip on

890

PHYSIOLOGY

the lower end of f is next closed, and the blood receiver now clipped at either
end, exhausted, detached from tube e, and weighed. A sample of blood is then
collected in the following way: — The arterial or venous cannula is filled with
blood, and immediately afterwards pushed into the rubber tube at the end of

Fig. 191.

Blood gas-pump of L. Hill. This consists of a mercury reservoir (a)
about 300 c.c. in capacity, which is connected with a second reser-
voir (b) by means of 120 cm. of pressure tubing. The upper end of
the reservoir (b) is closed by a three-way tap (n). By means of this
tap the reservoir (b) can be put in connection with either the tube (e)
leading to the blood receiver (f), or with the tube (c) leading to the
eudiometer (h). The tubes e and c are made of manometer tubing.
The blood receiver (f), which also acts as the froth chamber, consists
of three glass bulbs connected by short and wide junctions. To
either end of the blood receiver is fixed a piece of pressure tubing,
provided with a screw clip.

the blood receiver, as far as the closed screw clip. Before the insertion of the
cannula, the end of the rubber tube is compressed with the fingers to exclude
the air within it. A sufficient quantity of blood is now withdrawn by opening
at the same time the screw clip, and the clip placed on the vessel of the animal.

RESPIRATION 391

The blood is defibrinated by shaking it with the mercury left within the blood
receiver for that purpose, and the latter is then again weighed. The weight of
the sample of blood is then obtained. The blood receiver is once more aflSxed
to the tube (k), in the dependent position shown in the figure, and the tube (e)
is exhausted. Finally, the screw clip between e and the blood receiver is
opened, and the gases are withdrawn and collected in the eudiometer. Since
the blood receiver hangs freely from the tube (e) by means of a piece of rubber
tubing, it can be both immersed in warm water, and shaken to facilitate tl: e
complete escape of the gases. The bulbous form of the blood receiver prevents
the blood from frothing over into the pump ; and if the action becomes too
violent, it can be immediately allayed by pouring a few drops of warm water on
to the tube (e). The bubbles are thereby driven back into the receiver, and the
pump is never fouled. The tap (d) is so manipulated that the gases only, and
not the water which condenses in the reservoir (b), are driven over into the
eudiometer. The water is turned back into the blood receiver. Three to four
exhaustions are sufficient to extract all the gases from about ten grammes of
blood. The gases are estimated by the potash and pyrogallic acid method.'

The composition of this gas varies considerably in venous,
but not so much in arterial blood.

The average composition of the gases of dog's blood is
given in the following table :

From 100 vols. May be obtained

Of oxygen 0£ carbon dioxide Of nitrogen

Of arterial blood . . 20 vols. . 40 vols. . 1 to 2 vols.
Of venous blood . 8 to 12 vols. . 46 „ . „ „

Measured at 760 mm. and 0° C.

Thus the analyses of expired air and of the gases of the
blood show clearly that the latter, in its passage through the
lungs, takes up oxygen and gives off carbon dioxide. In
the tissues the reverse process occurs, so that the venous
blood returns to the lungs deprived of a portion of its
oxygen, and loaded with CO.. In studying the mechanism
of this gaseous interchange, it will be convenient to treat
the two gases separately, since their behaviour in the blood
and tissues seems to be largely independent of each other.

The oxygen in the blood is nearly entirely carried by
the haemoglobin of the red blood-corpuscles. The serum or
plasma of the blood cannot take up more oxygen than the
same bulk of water — less than 1 per cent, at the ordinary
atmospheric pressure and temperature. On the other hand,
if from a given specimen of blood we extract the haemo-
globin and dissolve this in water, we find that the pure
haemoglobin is able to absorb as much oxygen as the original
blood on being exposed to or shaken with pure oxygen or air.

392 PHYSIOLOGY

What is the condition of the ox3^gen in the blood ? Is it
simply dissolved, or does it enter into chemical combination
with the haemoglobin ?

It is well known that, when a gas is dissolved by a liquid,
the amount of gas taken up by the liquid varies directly as
the pressure of the gas. Thus if one hundred volumes of
water at 0° C. would dissolve four volumes of oxygen at a
pressure of one atmosphere, it would dissolve eight volumes
at a pressure of two atmospheres. At a pressure of three
atmospheres the amount dissolved would be twelve volumes.
If the liquid be removed from an atmosphere of oxygen at
a pressure of two atmospheres to an atmosphere at a pressure
of one, oxygen will be given off by the water until equilibrium
is established between it and the surrounding medium ; the
water will then contain only four volumes per cent. At a
pressure of half an atmosphere the amount dissolved will be
two volumes. In this case it makes no difference to the
amount of oxygen dissolved, whether the oxygen is alone or
whether it be mixed with some other gas. Thus the amount
dissolved will be the same, whether the water be exposed to
pure oxygen at a pressure of 380 mm. Hg, or to a mixture
of equal volumes of oxygen and nitrogen at a pressure of
760 mm. Hg. In each case the jjartial pressure or tension
of the oxygen is the same, and therefore the same amount is
dissolved.

When equilibrium is established between a gas and a
liquid, so that no gas is being taken up or given off by the
liquid, the tension of the gas dissolved in the fluid is equal
to that in the gaseous medium. On this fact is based the
meth(<d of determining the tension of a gas dissolved in
liquid. The liquid is brought into contact with gaseous
mixtures containing various proportions of the gas in question.
It is found that the liquid gives off gas to some of these
mixtures, and from others takes up gas. By making various
experiments a gaseous mixture will be found with which the
liquid is in equilibrium. If we know beforehand the amount
of gas in this gaseous mixture, we know its tension and
therefore the tension of the gas in the liquid.

Pfliiger's aerotonometer (Fig. 192) consists of two glass tubes, r and e,
contained in a vessel filled with water at the temperature of the body. The
upper ends of the tubes are connected by the tube a with the artery or vein

RESPIRATION

393

in which it is desired to estimate the tension of the blood gases. If for instance
we wish to determine the tension of CO2 in venous blood, where we expect the
tension to amount to about 4 per cent, of an atmosphere, one tube k is filled
with a gaseous mixture containing 3 per cent. C0„, and the other tube n with a
mixture containing 5 per cent. C0„. a is now connected with the distal end of
the jugular vein, or with the central end of the carotid artery, and blood is

Fig. 192.

Pfliigev's aerotonometer.

allowed to ilow and pass in a thin stream down the walls of the tubes r and i;,
thus presenting a large surface to the contained gases. The blood collects in
the lower narrower portions of the tubes, and runs out into the vessels b, b,
whence after defibrination it is returned at intervals into the veins of the
animal. Details of an experiment of this description carried out by Fredericq,
using however a single instead of a double tube, will serve to illustrate the
method employed.

Determination of Tension of Gases in Arterial Blood
Dog, 12 kilos. Received injection of ' peptone ' at 2.15 p.m.

2.34—3.34

3.36—4.36

Percentfige composition of gas in
aerotonometer

At beginning

C0.,= 5-07
O. = 10-8

co;=riv53~

0„ = 15-175

At end

C0o= 2-106

0^^13-01

"C'07^~2^2^

0.,= 14-83

Probable value of 0„ and CO2

tensions (in percentage of

an atmosphere)

O, = 13 to 14-8 per cent.
CO., = 2-41 per cent.

In this experiment the COo tension of the blood was lowered in consequence
of the injection of albumoses.

394 PHYSIOLOGY

One grm. of crystallised haemoglobin can absorb about
1'4 c.c. of oxygen. If a solution of this oxyhsemoglobin be
subjected in an air-pump to gradually diminishing pressure
at the temperature of the body, it will be found that very
little oxygen is given off until the partial pressure of the
oxygen is diminished to about 30 mm, Hg. At this point
a large evolution of gas begins, and continues at falling
pressure until at 0 mm. pressure all the oxyhaemoglobin is
dissociated and converted into haemoglobin. The same obser-
vation may be made in a reverse direction. If a solution
of reduced hemoglobin be exposed to gradually increasing
pressures of oxygen, it will be found that the greatest absorp-
tion takes place between 0 and 30 mm. Hg. After this point
the oxygen is very slowly absorbed, and the further absorp-
tion goes on in proportion to the partial pressure of oxygen.

The following table gives the relative proportions of haemoglobin and
oxyha3moglobin in a blood containing 13 per cent, hasmoglobin and exposed to
air at various pressures at a temperature of 37'4° C. (Hiifner).

Atmospheric pressure
in mm. Hg

760

Partial pressm
Oxygen in mm.

160

•e of
Hg

Hremoglobiu
percentage

5-4

Oxyha3moglobiu
percentage

94-6

524-8

110

7-6

92-4

357-8

75

10-8

89-2

238-5

50

15-4

84-6

119-3

25

26-7

73-3

47-7

10

47-6

52-4

23-8

5

63-9

36-1

0-0 ... 0-0 ... 10000 ... 0-00

In the curve in Fig. 193 the divisions along the base line correspond to the
partial pressure of the oxygen in mm. Hg, and those along the upright lines
(the ordinates) to percentage of saturation of the haemoglobin with oxygen.

In the case of simple solution, the relation between the pressure of a gas
and the amount absorbed would be represented by a straight line.

Since there is no direct proportion between the partial
pressure of the oxygen and the amount absorbed, it is
evident that the oxygen combines with haemoglobin to form
an unstable chemical compound, and that this is not a mere
question of solution. This is further proved by the fact
that we can displace the oxygen (O2) from the oxyhaemoglobin
by equivalent amounts {i.e. by equal volumes) of CO or NO.

A knowledge of these facts makes it easy to understand
how the oxygen is taken up by the blood as it circulates
round the pulmonary alveoli. Arterial blood, such as that

RESPIRATION

B95

which hlls the puhnonary vems and the systemic arteries, is
very nearly saturated with oxygen, and will only take up
about 1 per cent, more on shaking it with air at the body
temperature. Venous blood requires 8 to 10 volumes per
cent, of oxygen to saturate it ; Init we have already men-
tioned that, at a tension of 30 mm. oxygen, the blood becomes
more than three-quarters saturated. The tension of oxygen in
the alveoli is considerably above this. In the trachea the ten-
sion of oxygen is about ^ of an atmosphere (since the air here
contains 16 volumes per cent.), and the tension in the alveoli

Fir,. 193.

30
8o

70
6o
50
40
30
20

_____

[■

^

'

,/-

^'

/

/

/

/

'

) I

0 a

0 3

0 -1

0 J

0 6

0 7

0 8

0 9

0 K

50 I

10 1

20 I,

}0 t

to I

5O Hi

0

Diagram from Hiifner, to show the percentage saturation of hannoglobin
with oxygen at different pressures of the gas.

will be only a little lower than this. If we take the oxygen
tension in the alveoli at I of an atmosphere,^ it will still be
something over 100 mm. Hence the venous blood brought
to the alveoli by the pulmonary artery will, on there coming
into intimate contact with the atmosphere, take up oxygen
from it to saturation, or to a point not far removed from it.

The blood, thus laden with oxygen, travels to the left side
of the heart, and from there is sent through the arteries to
all parts of the body. It must be remembered that neither

' The oxygen tension in the alveoli has been reckoned at about 12-G per
cent, to 13-5 per cent, of an atmosphere.

896 PHYSIOLOGY

in the lungs nor in the tissues does the haemoglobin come m
actual contact with the source of the oxygen, nor with the
cells which it is to supply. In both cases the interchange is
effected through the intermediation of the plasma and, in
the tissues, of the lymph as well. Since the tissue-elements
are constantly using up oxygen, which they build up into
their living protoplasm, they absorb any oxygen that is
present in the surrounding lymph. There is, in consequence,
a descending scale of oxygen tensions from red blood-cor-
puscle through plasma, vessel-wall, lymph, and tissue-element.
The cell draws from the lymph, the lymph from the plasma,
so that the oxygen tension in the plasma sinks. This has the
same effect as if we put the red corpuscles in a mercurial
pump and lowered the pressure of gas. The immediate result
is an evolution of oxygen, which is taken up by the plasma, to
be in turn passed on to the lymph and the tissue-cell.

Under normal circumstances a blood-corpuscle never
stays long enough in the proximity of the tissues to lose its
whole store of oxygen. If however the further supply of
oxygen to the blood be prevented, as in asphyxia, the last
traces of oxygen disappear from the blood. The enormous
avidity of the tissues for oxygen is shown by the following
experiment (Ehrlich). If a saturated solution of methylene
blue be injected into the circulation of a living animal and
the animal be killed ten minutes later, it is found on first
opening the body that most of the organs present their
natural colour, although the blood is a dark-blue colour. On
exposure to the atmospheiie all the organs acquire a vivid
blue colour. The avidity of the tissues for oxygen has been
so great that they have been able to decompose the
methylene blue molecule, with the formation of a colourless
reduction-product, which on exposure to the air undergoes
oxydation again and reforms methylene blue. If then the
tissues are able to effect the reduction of a comparatively
stable body like methylene blue, it is easy to understand their
power of reducing oxyhemoglobin, which is so unstable that
it is decomposed by simple physical means such as exposure
to a vacuum.

It was long debated whether the chief processes of oxida-
tion took place in the blood or in the tissues. Our experi-
ences with muscle would alone serve to convince us that in

RESPIRATION 397

some tissues, at any rate, processes of oxidation take place,
and the methylene blue experiment shows that these pro-
cesses of oxidation are intense in all the chief organs of the
body. It has been found moreover that it is possible to keep
a frog alive after substituting normal saline solution for his
blood, if he be placed in absolutely pure oxygen, and that in
this case indeed the metabolism of the animal goes on as
actively as before. As the frog has no blood, it is evident
that its metabolic processes, consisting of the taking up of
oxygen and the giving out of carbon dioxide, must have their
seat in the tissues.

The relations of carbon dioxide in the blood and the
manner of its excretion through the lungs are rather more
complicated and obscure than in the case of oxygen. If a
given volume of blood be divided into plasma or serum and
corpuscles, it will be found that the larger proportion of the
carbon dioxide in the whole blood is contained in the serum,
although a certain amount is also present in the corpuscles.
When extracting gases from serum by means of the mercurial
pump, it is found that about 5 per cent, of the carbon dioxide
present is fixed ^ — that is to say, is only liberated after the
addition of some weak acid, such as phosphoric or tartaric
acid. If however we use whole blood for the experiment, it is
found that the entire amount of CO., is given off. This is
shown by the fact that, after extracting with the pump as
much CO.^ as possible, no further amount can be obtained on
addition of phosphoric acid. Hence the red corpuscles act the
part of a weak acid, and we can, in fact, in the first experiment
use fresh red corpuscles instead of phosphoric acid to drive
off the last trace of CO,.

From 100 volumes of venous blood we can extract about
50 volumes of CO.. The question now arises : Is this gas in
a condition of solution or in chemical combination with the
plasma ? The answer is easy to give. At the temperature
of the body 100 volumes of plasma would take up 50 volumes
of CO2 at 760 mm. Hg pressure, i.e. if we may consider the

• It must not be thought that these 5 volumes per cent, represent the whole
of the CO. that is chemically combined. The fact that a part of the gas is
given off on exposure to a vacuum, and a part left in solution, shows merely
either that one part is in a state of looser chemical combination than the other,
or that the phosphates in the serum only suffice to take up part of the soda
liberated by the decomposition of the sodium carbonate.

398 PHYSIOLOGY

solubility of the gas in plasma equal to its solubility in water.
If therefore CO.^ exists in a state of solution in the plasma,
its tension will be 760 mm. Hg, that is to say, one atmosphere.
Now the CO., tension in venous blood may be determined by
the method indicated later (p. 417), and is found to be equal
to only 5 per cent, of an atmosphere. This merely means
that when the venous blood is brought into an atmosphere
containing 5 per cent. CO^, the relative proportions of CO,^
in the liquid and the gas remain the same. We see then that
only ^ part of 50 volumes can be absorbed, since the CO2
tension is only -^ of an atmosphere ; and must conclude that
of the 50 volumes |-|} = 2^ volumes are in simple solution,
and the remaining 47^ volumes in chemical combination.

On analysing the ash of the serum, we find that it con-
tains sufficient sodium present to combine with all the CO.^,
besides that which is necessary to satisfy the fixed acids,
hydrochloric and phosphoric. The presence of phosphates
as well as proteins (which may act as weak acids) in the
serum is probably of great importance for the regulation
of the tension of the 00.^. If the two acids, carbonic and
phosphoric, are present together in a solution containing soda,
the salts formed depend on the relative masses of the two
acids. If the carbonic acid is in excess, sodium carbonate is
formed, together with monosodium phosphate (NaH.^PO,). If
however the carbonic acid be removed, or its ' mass influence '
diminished by allowing it to escape freely into a vacuum, the
phosphoric acid gains the upper hand and takes the lion's
share of the sodium, disodium phosphate (Na^HPO^) being
formed. In this way, as soon as the amount of free carbon
dioxide decreases, however little, the amount of the CO.^ in
combination also diminishes, and moreover to a very con-
siderable extent. Thus in the serum, where these two salts
are present, an alteration of eight volumes per cent, in its CO2
gives rise to a change of tension of only 2*6 per cent, of an
atmosphere.

In other words a distinct advantage is gained if the CO2 in the plasma is, like
the oxygen in the corpuscles, in a condition of unstable chemical combination.
A rise of oxygen tension from 0 to 25 mm. gives a rise of oxygen carried from
0 vols, per cent, to 15 vols, per cent, (taking 20 vols, per cent, as maximum satura-
tion of the hemoglobin), while a rise of COo tension from 0 to 38 mm. gives an
increase in CO^ carried in the plasma from 0 vols, to 50 vols, per cent. If the
CO., were in simple solution, this change of tension would raise the CO.^ content

EESPIRATION 399

only to 2^ vols, per cent. The co-existence of other weak salts of sodium, such
as phosphate or albuminate, with the carbonate has the eil'ect of rendering the
latter more unstable and more susceptible to changes in mass action of CO^,
i.e. to changes in the CO.j tension.

This struggle between the COo and the weak acids of the
serum for the possession of the sodium is constantly going on.
In the tissues, where the CO^ tension is high, the mass influ-
ence of this acid predominates, and a large amount of it is
taken up into the blood, where it forms sodium bicarbonate.
It is difficult to be certain of the tension of the carbon dioxide
in the cells themselves. In urine it is 9 per cent., and in bile
7 per cent. It may be estimated in the tissues of the intestinal
wall of an animal such as the rabbit, with a thin -walled gut,
by injecting air into a ligatured loop of intestine, and
analysing the air after two or three hours. The air is then
found to contain 7 to 8 per cent. COo. Thus the tension is
much higher in the tissues than even in the venous blood, and
there must be a continual flow of CO^ from tissues to lymph,
and from lymph to blood-plasma.

We have seen above that the taking up of oxygen by
the blood in the lungs can be explamed on purely physical
grounds, since the tension of oxygen in the alveoli is suffi-
cient to cause almost complete saturation of the haemoglobin.
Our experimental data however do not yet suffice to show
that the physical conditions at work account for the giving
off of CO^, to the air in the alveoli. In order that this might
happen by a mere process of gaseous diflusion, the following
conditions must be present.

The tension of the carbon dioxide in the pulmonary
alveoli must always be less than that in the blood. If this
be so, the blood in its passage through the pulmonary capil-
laries will give oft" COj to the alveolar air, and the COo tension
in the blood will be diminished. But this discharge of COo
can never go on to such an extent that the COj tension in the
blood should fall below that in the alveolar air ; for if this
were the case there would be at once a retrograde movement
of the CO.^, which would then pass from the alveolar air
back to the blood. Thus the COo tension in the blood of
the pulmonary vein can never be less than that of the
alveolar air.

The experimental investigation of this question is not

400 PHYSIOLOGY

entirely satisfactory. According to Pfliiger and Fredericq,
the output of carbon dioxide as well as the intake of oxygen
in the lungs can be accounted for by simple processes of
diffusion. The basis for this statement lies in the determi-
nation by aerotonometric methods of the tensions of oxygen
and CO2 in venous blood, in arterial blood, and in alveolar
air. The average results obtained by these methods are as
follows :

Arterial blood . . . 2-8 per cent. ]

Venous blood . . . 3-5 — 5'4 per cent. V from dog.'

Alveolar air .... 2-8 per cent. j

It would seem from these figures that the interchange of
gases in the lungs was practically complete, and such a result
is not surprising when we consider that the surface area of
blood exposed in the alveoli of the lungs amounts to 2,000
square feet, every blood-corpuscle being practically exposed
on two sides to the alveolar air.

Objections have however been raised to these results. It has been pointed
out that the tension of oxygen in the blood, even in the arteries, must be con-
stantly and rapidly diminishing as the blood leaves the lungs, while the tension
of CO^ must increase in a like manner, although to a less degree, since it
is found that any delay in the pumping of the gases out of the blood leads
to a diminution of total oxygen and to an increase of CO.^. This slight loss
of oxygen, in consequence of processes of oxidation going on in the blood
itself, would cause a considerable change in the oxygen tension, and must
therefore diminish the value of the results obtained by the aerotonometer. In
order to avoid this source of fallacy, Haldane has devised a method of deter-
mining the oxygen tension of the blood in the lungs, founded on the use of
carbon monoxide.

It has already been mentioned that carbon monoxide has the power of
displacing oxygen from oxyha-moglobin to form a much more stable com-
pound, carboxyhromoglobin. If blood be shaken up with a mixture of oxygen
and carbon monoxide, the hiemoglobin distributes itself between the two
gases. In order however to get an equal distribution, it is necessary 10 take
a very small percentage of carbon monoxide, owing to its greater avidity for
ha;moglobin. Thus if hsimoglobin solution be shaken up with air containing
0-07 per cent, of CO, the result is a mixture of equal parts of oxy- and carb-
oxyhsemoglobin. The affinity of CO for haemoglobin would thus appear to

21

be about = 300 times the affinity of oxygen for haemoglobin.

Carbon monoxide however is not destroyed in the body, so that if a mixture
containing a small proportion of CO be breathed, this gas will be taken up until
a certain percentage of hemoglobin is converted into CO hsemoglobin and the

' The dog in these experiments was curarised, and artificial respiration was
employed. On this account the amounts of CO^ in the expired air and in the
blood were reduced below normal.

RESPIEATION 401

tension of CO in the tissues and fluids of the body is equal to that of the
inspired air. The amount of haemoglobin therefore, which is converted into
carboxyhsemoglobin, will serve as a measure of the relative tensions of CO
and oxygen in the lungs. If the oxygen tension of arterial blood wei'e the same
as that of air, we should expect that, with a given percentage of CO in the air
breathed, the final saturation with CO of the blood within the body would be the
same as the saturation of blood when shaken outside the body with air con-
taining the same percentage of CO as in the air breathed. It was found by
Haldane however that in all cases the percentage of CO hemoglobin formed was
much less in the body than outside the body. Thus in blood shaken up with
air containing 20"9 per cent, oxygen and 0'04.5 per cent. CO, the amount of
carbon monoxide formed was 31 per cent, of the whole haemoglobin. When
the same mixture was inhaled for three or four hours by a man, the percentage
of CO haemoglobin in his blood rose only to 26 per cent., at which figure it
remained stationary. This would correspond to an oxygen tension of about
25 per cent, of an atmosphere, whereas we have already seen that the oxygen
tension in the alveoli cannot be greater than 15 per cent. Hence it would appear
that the epithelial cells of the alveoli play an active part in the respiratory inter-
change, taking up the oxygen on one side at a tension of 15 per cent, and piling it
up on the other until the pressure in the blood is double that in the alveolar air.
Theoretically there is no reason to deny the possibility of such powers to the
pulmonary epithelium. We know that the secreting cells of the kidney take up
urea from the blood which contains only about 0"05 per cent, of this substance,
and excrete it into the renal tubule, into a medium containing about 2 per cent. ;
and if the data given by Haldane are correct, we must ascribe an analogous
function to the pulmonary epithelium. These data however were obtained by
a colorimetric method working with very minute quantities of blood, and in
the absence of further control experiments the question must be regarded as
undecided.

I have already mentioned that part of the carbon dioxide
in the blood is in combination with the red blood-corpuscles.
A solution of hsemoglobin is also found to have a power of
combining with CO.^ to form a loose chemical compound. It
is thought by some that this carbon dioxide haemoglobin acts
as a carrier of CO., between the plasma and the alveolar air,
and that, under the influence of the oxygen of the alveolar
air, the CO.^ is expelled from the corpuscles, causing a sudden
rise of CO^, tension in the plasma, and therefore a discharge
of this gas into the alveoli.

26

402 PHYSIOLOGY

Section 3
THE EEGULATION OF EESPIRATION

For the normal carrying out of respiration a complicated
series of co-ordinated movements is necessary. And this
is not all. The respiratory movements must be adjusted in
rhythm and strength to the varying needs of the organism.
When the animal is performing active work, when the muscles
of the body are contracting vigorously and producing large
quantities of carbon dioxide, the respiratory movements must
be also quickened and deepened in order to provide for the
due aeration of the blood, and the discharge of the excess of
carbon dioxide produced.

This co-ordination of the activities of the respiratory
muscles and their adaptation to the varying needs of the
organism are brought about through the agency of the
nervous system, and in particular by a circumscribed portion
situated in the medulla oblongata.

If a section be made just above the pons dividing the brain
from the lower parts of the central nervous system, it will
be observed that the respiratory movements go on normally.

If another section be made at the lower border of the
medulla, the diaphragm and ribs will be motionless, but
respiratory movements may be still observed to take place in
the facial muscles and larynx. These experiments show that
the part of the nervous system presiding over the movements
of respiration is situated somewhere between the two sections.
This * centre ' can be localised still more exactly. Injury to a
small portion of the medulla in the immediate neighbourhood
of the nuclei of the vagus nerves, and just below the vaso-
motor centre, causes total cessation of resj^iratory movements
and death of the animal. Hence this part of the nervous
system was called by Flourens, its discoverer, the noeud
vital.

In new-born animals a few abortive attempts at respira-
tion are sometimes observed even after destruction of this
centre ; and it is therefore supposed that there are subsidiary

RESPIRATION 403

centres in the cord controlled and regulated by the centre in
the medulla. This is true, since the anterior cornual cells,
whence the motor fibres to the respiratory muscles arise, are
situated all the way down the cord. But these are not
res])hratonj centres, since respiration involves a co-ordination
of the various motor centres. The spasmodic movements
that may occur under the influence of strychnine or asphyxia
after destruction of the medulla are not co-ordinated, inspira-
tory and expiratory muscles contracting at irregular intervals
and in many cases simultaneously.

The question now arises whether the activity of this
centre in the medulla may be regarded as automatic or
reflex : that is to say, do the rhythmic discharges proceed-
ing from it depend merely on local changes taking place in
the centre, induced perhaps by changes in the surrounding
lymph or blood, or on a rhythmic or continuous excitation of
the centre by stimulation of some afferent nerve? If the
vagus nerves be cut and the spinal cord divided just below
the medulla, respiratory movements of the alae nasi are seen
to continue and to grow more pronounced as the blood
becomes venous in consequence of the cutting off of the chief
respiratory muscles from the medullary centre.

A still more thorough isolation of the centre has been
accomplished by dividing the vagi, cutting through the upper
part of the medulla and through the cord at the first dorsal
nerve, and then dividing all the cervical posterior roots. In
this case movements of the diaphragm still continued, but
consisted simply in a series of prolonged spasms, at first
about two to four per minute and gradually getting less fre-
quent till the animal died. We might argue from this that
the centre was capable of a very imperfect degree of auto-
matic action, but needed the stimulus of afferent impulses from
the vagi or from the higher parts of the brain to render these
actions adequate for the respiratory needs of the organism.

In the above experiment the centre cannot be regarded as free from all
afferent stimuli, since the mere closure of the demarcation current in the cut
ends of the nerves would cause a certain amount of excitation, and the animal
does not survive sufficiently long to allow this condition to pass off. Hering
has shown that in the ' spinal cord frog ' {i.e. one in which the brain has been
destroyed) section of all the posterior roots absolutely destroys all mobility, the
injection of strychnine being without effect. A typical spasm however can be
at once produced by exposing and stimulating the stump of one of the cut
posterior roots. We might suppose that the respiratory centre would be

404 PHYSIOLOGY

siniihirly devoid of automatism if absolutely free from afferent stimuli." It can
be shown however that the centre tends to respond to all stimuli, continuous
or rhythmic, by means of rhythmic discharges.

Whether or no we accept as proved the possible auto-
matism of the centre, there is no doubt that the activity of
the centre is intimately dependent on its local chemical state
or environment.

If, the nervous centres being intact, the proper aeration
of the respiratory centre be interfered with in any way, as by
obstruction of the respiratory passages, or by perforation of
both pleura, or by ligature of all the arteries to the brain, or
by extensive loss of blood, the respiratory movements increase
in strength and frequency, and if the disturbing factor be not
removed the animal dies, presenting a train of phenomena
which are classified together under the term ' asphyxia.'

The phenomena of asphyxia may be divided into three
stages :

(1) In the first stage, that of hyperpnoea, the respiratory
movements are increased in amplitude and in rhythm. This
increase affects at first both inspiratory and expiratory
muscles. Gradually the force of the expiratory movements
becomes increased out of all proportion to the inspiratory,
and the first stage merges into :

(2) The second, which consists of expiratory convulsions,
in which almost every muscle of the body may be involved.
Just at the end of the first stage consciousness is lost, and
almost immediately after the loss of consciousness we may
observe a number of phenomena extending to almost all the
functions of the body, some of which have been already
studied. Thus at this time the vasomotor centre is excited,
causing universal vascular constriction. There is often also
secretion of saliva, inhibition or increase of intestinal move-
ments, constriction of the pupil, and so on.

(3) At the end of the second minute after the stoppage
of the aeration of the blood, the expiratory convulsions cease
almost suddenly, and give way to slow deep inspirations.
With each inspiratory spasm the animal stretches itself out.

' According to Sherrington, it is possible to excite strychnine or asphyxia
!ipasms in a dog or cat with isolated spinal cord, in which all the afferent roots
below the transection have been divided six or seven hours previously. These
experiments appear to indicate that in the mammal the motor nervous
mechanisms can be set into activity apart from the incidence of afferent
impressions.

RESPIRATION 405

and opens its mouth widely as if gasping for breath. The
whole stage is one of exhaustion ; the pupils dilate widely,
and all reflexes are abolished. The pauses between the
inspirations become longer and longer, until at the end of four
or five minutes the animal takes its last breath.

Somewhat similar movements of respiration, but on a
smaller scale, may be produced b}^ increasing the activity of
the centre, and therefore its gaseous interchanges, by warm-
ing the blood m the carotid arteries on its way to the brain.
Under these circumstances there may be a considerable
quickening of respiration unaccompanied by any deepening,
which is often spoken of as tacliypnoea. On the other hand,
we may slow the respiratory movements by placing a small
piece of ice on the floor of the fourth ventricle.

In the production of the phenomena of asphyxia two
factors must be at work. In the first place there is an
accumulation of carbon dioxide in the blood bathing the
centre or an increased tension of this gas in the centres
themselves, either as a result of deficient excretion or
increased production. On the other hand, the centre is
deprived of oxygen, either by failure of renewal of the oxygen
supply, or by increased using up of this gas in the metabol-
ism of the centre. The question arises. Which of these two
changes is responsible for the different phj'siological events
which characterise asphyxia ? At various times these
phenomena have been ascribed either to the increased
tension of CO^ or to the diminished tension of oxygen in the
centre. As a matter of fact, both factors are at work, and we
must now proceed to discuss the exact part played by each.
In order to investigate this point we may try the effect on the
respiratory movements of altering the tension of these two
gases in the air breathed. The results of such experiments
are very striking. It is found that even a slight increase in
the percentage of CO., in the air causes an increase first in
the depth and later on in the rhythm of respiration. This is
well shown in the following Table by Haldane, which repre-
sents the average depth and frequency of the respirations
when the subject was breathing normal air and air charged
with varying percentages of CO.. It is seen that a rise of
COo in the atmosphere to 2 per cent, increases the depth of
respirations by 30 per cent., and the total alveolar ventilation

40G

PHYSIOLOGY

by 50 per cent. A rise of CO.^ to 3 per cent, increases the
total ventilation of the alveoli by 126 per cent. An amount
of CO., equivalent to 6 per cent, increases the depth of each
respiration by 27'2 per cent., and the total alveolar ventilation
by 757 per cent.

Percentage CO.,

Average depth

Average
frequency of

Ventilation of Alveoli

with inspired Air,

(Normal =100)

100

COj Percentage

in inspired Air
0-04

of Respirations

Jiesjiirations
per Minute

14

in Alveolar Air

673

5-6

((■(•(JO litres per rain.)

0-79

789

14

lie

5-5

202

864

15

153

5-6

307

1,216

15

220

5-5

5-14

1,771

19

498

G-2

6-02

2,104

27

857

6-6

If we examine the last column of figures in this Table,
representing the percentage of CO.; in the alveolar air, it will
be seen that, in spite of the very large variations in the air
breathed, the alveolar content in CO^ remained practically
constant until the CO^ in the atmosphere was increased to
such an extent that the processes of compensation were no
longer efficient. We must conclude therefore that the
respiratory centre is so arranged as to react to the slightest
increase of CO2 tension in the blood, any increase in this
gas giving at once a compensatory increase in depth and
frequency of respiration, so that the alveolar CO., content may
be maintained almost constant.

That it is the tension of CO.^ in the alveolar air, and
therefore in the blood bathing the centres, and not the per-
centage amount of this gas, which is the determining factor,
is shown by a comparison of the composition of the alveolar
air under different atmospheric pressures. Thus, when the
subject of the experiments, from which the above Table was
derived, was placed in an air-chamber compressed to a
pressure of 1,261 mm., the mean percentage of CO^ in the
alveolar air was 3*42, corresponding, however, to a tension of
5-6 per cent, of an atmosphere, a figure almost identical with
those given in the last column of the Table above. At the top
of Ben Nevis, where the barometric pressure was 646 mm. the
percentage of CO.^ in the alveolar air was 6*6, corresponding
to a tension of 5-2 per cent, of an atmosphere, i.e. of 760 mm.

RESPIKATIOM 407

Thus the pressure of CO., in alveolar air remains practically
constant with widely varying limits of atmospheric pressure
and with very different percentages of CO, in the inspired
air, showing that the reactions of the organism are directed
so as to maintain, by alterations in the respiratory depth and
rhythm, a constant tension of this gas in the alveoli.

Very different are the phenomena observed on alteration
of the partial pressure of oxygen. Here, within wide limits,
the partial pressure of oxygen in the alveolar air is deter-
mined by its pressure in the inspired air. Thus, if we take
the same series of observations, with a pressure of 646 mm.,
the percentage of oxygen in the alveolar air was 13* 19,
corresponding to a tension of 10"4 per cent. At an atmo-
spheric pressure of 755 mm. the percentage of oxygen in the
alveolar air was 13*97, corresponding to a tension of 13'06
per cent. In air compressed to a pressure of 1,260 mm. the
percentage of oxygen was 16*79, corresponding to a tension of
26*8 per cent, of an atmosphere of 760 mm. The same sort
of results are obtained by altering the percentage of oxygen
in the air breathed. It is found that the oxygen tension or
percentage in the inspired air can be lowered from its normal
of 20*93 to 12 or 13 per cent, without altering in any way
the depth or rhythm of respiration, and in fact without any
change being noticed by the individual who is the subject
of the experiment. A percentage of 13 per cent, of oxygen
corresponds to an alveolar content in oxygen of 8 per cent.,
and with a further reduction of the oxygen content there
is increased pulmonary ventilation, but the diminution in
oxygen may be pushed to such an extent that the patient
becomes blue from the deficient aeration of his haemoglobin,
without any considerable distress being caused. In fact, in
many cases, the subject of such an experiment may lose con-
sciousness suddenly, before he has been aware of any serious
deficiency in his aeration. We must conclude, therefore, that
the respiratory centre possesses a specific excitability for
carbon dioxide, and that it is by this specific excitability that
the normal depth and rhythm of the respiratory movements
are determined. The uses of such an excitability to the
organism are obvious.

We may take as an example the changes in respiration
which occur in an animal as the result of muscular exercise.

408 PHYSIOLOGY

Under normal circumstances any changes in the amount of
oxygen in the air breathed will be of the rarest possible
occurrence. As the result of muscular exercise a large
amount of carbon dioxide is produced in the muscles. The
venous blood passing from the muscles to the lungs will
therefore be more highly charged with this gas, and a rapid
rise in the alveolar CO., pressure, and therefore in the arterial
CO,, pressure, will be occasioned. The respiratory centre is
thus stimulated to increased activity, with consequent lower-
ing of the alveolar CO., pressure, until a point is reached at
which an equilibrium is maintained between the effect of the
increased production of CO.2 in raising the arterial CO.^ pressure
and that of the increased respiratory activity in lowering it.

In certain experiments by Zuntz and Geppert on the causation of the
increased respiratory movements during muscular exercise, these observers
found that the movements were increased to such an extent as to bring the
amount of CO.^ in the arterial blood below the normal. In these experiments,
however, the muscular contractions were not produced by normal exercise, but
were obtained by tetanising through the spinal cord the lower limbs of an
animal. Under these circumstances, the activity of the muscle would be
associated with a diminished blood-flow, so that the contractions would be carried
out in the absence of a sufficient amount of oxygen. As we have seen earlier
in dealing with the metabolism of muscle, in the absence of sufiicient oxygen,
muscular contractions result in the production, not of CO.j, but of lactic acid,
and it is highly probable that, in the experiments in question, there was a
discharge of acid substances into the blood, diminishing the alkalinity of this
fluid and therefore lowering its carrying power tor CO.^. As a matter of fact,
one can produce dyspnoea by diminishing the alkalinity of the blood by the
injection of acids, and attacks of dyspnoea are observed in the later stages of
diabetes, when the alkalinity of the blood is decreased in consequence of the
enormous production of such bodies as oxybutyric acid. A diminished carry-
ing power of the blood for CO., will necessarily raise the tension of this gas in
the tissues where it is formed, and a diminished alkalinity of the blood will
therefore tend to cause a higher tension of CO2 around the respiratory centre.
It is probable that when muscular exercise is carried to exhaustion, this
diminishing of alkalinity of the blood also plays its part in the hyperpnoea and
dyspnoea, but in every case the determining factor seems to be the increased
tension of the CO.^ in the respiratory centre itself. We must therefore con-
clude that the depth and rhythm of respiration — that is, the regulation of the
rate of alveolar ventilation and of respiration — depend under normal conditions
on the CO.2 pressure in the respiratory centre. This part of the central nervous
system has developed a specific sensibility for COj, a rise of 0'2 per cent, of
an atmosphere in the tension of this gas in the alveoli, and therefore in the
arterial blood, being sufficient to double the amount of alveolar ventilation
during rest.

It is only the first phase in the phenomena of as^jhyxia which is thus
conditioned by the changes in the CO.^ tension. The respiratory centre shares
with the rest of the central nervous system a sensitiveness to the absence of

RESPIRATION

409

. /»3 n, deprivation of oxygen having tirst an excitatory and later a paralytic
ect. In asphyxia the first centres to feel this effect are those of the cortex,
d during the first stage there is mental excitation terminating rapidly in
abolition of consciousness at the end of this stage. During the second stage
here is a discharge of energy, which spreads throughout the whole nervous
system, beginning in the bulbar centres and causing a great rise of blood
pressure with slowing of the heart, and extending thence to all the spinal
centres with the production of muscular spasms. At this stage, too, there is a
discharge of impulses giving contraction of the pupil, and a little later dis-
charge along the whole sympathetic system producing the various phenomena
of vaso-constriction, erection of hairs, sweating, salivation, which are generally
brought about by stimulation of different parts of this system. The phenomena
of the third stage are due to a gradual exhaustion of the nerve-centres, accom-
panied or preceded by an exhaustion and dilatation of the hea»t, the circulation
failing before the excitation of the lower centres has entirely come to an end.
In this third stage, however, it is impossible by the strongest stimuli to evoke
any reflex, and the general phenomena are those of exhaustion.

Although we must regard the specific sensibihty of the
respiratory centre to COo as the most important factor in
determining the depth and rhythm of the respiratory move-
ments, these movements and the condition of the respiratory
centre itself are modified in a large degree by impulses arriv-
ing at the centre along both vagi. Through other sensory
nerves of the body the respiratory movements can be altered
reflexly, but it is only through the vagi that a continuous
stream of impulses passes to the centre under normal circum-
stances, so that exevy respiratory movement is modified by
these impulses.

iuG. 194.

/]

Normal tracing of diaphragm slip (Head's method).

In studying the nervous mechanism of respiration, it is necessary to have
some accurate method of recording the resisiratory movements. They may be
registered by means of a tambour applied to the chest, communicating with
another tambour provided with a lever, which is arranged to write on a
blackened surface ; or a side tube to a cannula in the trachea may be con-
nected with the registering tambour. In the first case, movements of the
thoi'ax are registered; in the second, changes of intra-pulraonary pressure.

410 PHYSIOLOGY

These methods are obviously useless when it is wished to study the effects of
artificial distension or collapse of the lungs. In this instance we may use the
ingenious method described by Head. In the rabbit a slip of the diaphragm
on either side of the ensiform cartilage is so disposed that the end of it may be
freed and attached by a thread to a lever without injury to its blood- or nerve-
supply. It is found that this slip contracts synchronously with the rest of the
diaphragm, so that it serves as a sample of the diaphragm, the coniractions-of
which may be recorded uninfluenced by passive movements of the chest-wall or
artificial increase of intra-pulmonf^ry pressure.

If, while the respiratory movements are being recorded
in one of the aforementioned ways, both vagi be divided,' a
marked change in the respiratory rhythm is at once seen

Fig. 195.

Tracings of respiratory movements. — A. Normal. B. After
• division of one vagus. C. After section of both vagi. D.

Both vagi cut. The central end of one vagus stimulated

with weak induced current at Exc.
Lower line = time-marking, indicating seconds. (From

Waller.)

(Fig. 195). The first effect is an increased inspiratory tonus,
but this rapidly disappears, and the respiratory movements

' The division of the vagi is best effected by putting them on a hooked
copper wire, of which the upper end is inserted in a freezing mixture. In
this way complete functional division of the nerves is obtained without any
excitation. If the nerves be cut, a certain amount of stimulation takes place
in consequence of the closure of the demarcation current produced by the
cross-section.

RESPIEATION 411

become less frequent and are increased in amplitude. If now
the central end of one of the vagi be stimulated with an
interrupted current, the respiration may be quickened (as in
the experiment represented in Fig. 195), or, as is more
commonly the case, the inspiratory movements may be
increased at the expense of the expiratory, so that finally
a condition of inspiratory standstill is produced, and the slip
of the diaphragm enters into prolonged contraction.

With a very weak stimulus it is sometimes possible to
produce augmentation of the expiratory movements or rather
inhibition of the inspiratory, and this is the invariable result
of passage of a constant current through the vagus in an
ascending direction. This effect however may be more
strikingly brought about by stimulation of the central end
of the superior laryngeal nerve. Excitation of this nerve pro-
duces first an inhil)ition of inspiration, so that the respiratory
muscles come to a standstill in the position of expiration, and
then a forcible contraction of the expiratory muscles takes
place. This illustration of the presence of expiratory fibres
in the superior laryngeal nerve is not confined to laboratory
experience, but is constantly occurring in everyday life.
The superior laryngeal nerve supplies sensory fibres to the
mucous membrane of the glottis, and we know that the
slightest irritation of these fibres — the presence of a crumb
or a particle of mucus — causes forcible expiratory spasms,
with spasmodic closure of the glottis, which we term a
cough.'

So we see that the vagus nerve contains two kinds of
afferent fibres, or at any rate afferent fibres with two distinct
functions. Stimulation of the one kind stops inspiration and
produces expiration ; stimulation of the other stops expiration
and produces inspiration.

Since section of both vagi causes slowing of respiration, it
is evident that, under normal circumstances, impulses which
exert some influence on the respiratory centre and quicken
respiration, must travel up the vagi from the lungs. The

' It must not be imagined that the fibres of the superior laryngeal nerves
are concerned in the reflex maintenance of the normal respiratory rhythm.
They are cited here merely because the result of their stimulation resembles
that which would be caused by stimulation of the analogous expiratory fibres
which run in the trunk of the vagus from the lungs to the respiratory centre.

412 PHYSIOLOGY

respiratory movements cause an alternate distension and
contraction of the Imigs, and it has long been thought that
it is these changes in the volume of the lungs which start the
accelerating impulses that travel up the vagus nerves. To
test the truth of this hypothesis it is necessary to study the
two phases of respiration separately ; that is, to see first the
result on the respiratory impulses of repeated distension of
the lungs, and secondly the result of a sudden collapse or a
contraction caused by sucking air out of the lungs. The first
mode of experiment, when air is driven repeatedly into the
lungs, is spoken of as positive ventilation ; and the second,
when air is sucked repeatedly out of the lungs, as negative
ventilation. In these experiments it is advantageous to
employ Head's method of registering the diaphragmatic
movements. If, in a rabbit breathing quietly, air be

Fig. 19G.

Pop. ventilation

Positive ventilation (Head). Under the influence of positive
ventilation, the inspiratory contractions of the diaphragm
become less and less till they disappear completely.

repeatedly blown into the lungs, the inspiratory movements,
as evidenced by the contraction of the diaphragm, are
gradually knocked down, till finally the animal is in a con-
dition in which no inspiratory movements whatever are made
(Fig. 196) ; or the diaphragmatic standstill may be followed
by a strong contraction of the expiratory muscles. Thus
distension of the lungs has the same effect as stimulation of
the superior laryngeal nerve in stopping inspiration and pro-
ducing expiration.

If, on the other hand, air be sucked out of the lungs at
regular intervals (negative ventilation), the movements of the
diaphragm are amplified, and it does not relax completely
after each individual respiration. The relaxation becomes
more and more incomplete, until finally the diaphragm enters

RESPIEATION 413

into a condition of continued contraction, which may last for
several seconds (Fig. 197). Thus collapse of the lung inhibits
expiration and augments inspiration.

The effects of distension or collapse of the lung may be
still more readily shown by simply closing the trachea at the
end of inspiration or of expiration. The results of such an
experiment are shown in Fig. 198.

These experiments throw complete light on the quickening
action of the vagus on respiration. Normal respiration is a
series of reflex acts. Each inspiratory movement causes an
expansion of the lung, which in its turn stimulates the vagus
nerve-endings, inhibiting the movemeiit which has given rise

Fig. 197.

Negative ventilation (Head). At a negative ventilation was
commenced. The expiratory relaxation of the diaphragm is
seen to become more and more incomplete, until it finally
enters into continued contraction.

to the stimulus, and causing the ensuing expiratory movement.
The collapse of the lung attending expiration acts like the
negative ventilation in the experiment above mentioned in
stimulating the inspiratory nerve-endings of the vagus ; and
the impulse thus produced acting on the medullary centre
checks the expiratory and hurries on the inspiratory move-
ment. In this way, under normal circumstances, the rhythm
of the respiratory centre is determined reflexly through the
agency of the vagi, while the chief factor in determining the
total pulmonary ventilation, i.e. the depth of the movements,
is the CO.^ tension of the blood.

In the foregoing account we have spoken of the expiratory and inspiratory
effects of the vagus as if they were of equal importance. It seems probable
however that the inhibitory or expiratory impulses started by the inspiratory
movement, the only active part of normal respiration, play a more prominent

414 PHYSIOLOGY

part in the regulation of respiration than do the inspiratory impulses; and
one observer (Gad) goes so far as to deny altogether the existence of two kinds
of respiratory fibres in the vagus. According to Gad, the vagus, as regards the
respiratory centre, is a purely inhibitory nerve. Hence the primary effect of
dividing both vagi is an increased inspiratory tone. This view at first seems
paradoxical, in that it explains the final slowing of respiration after section of
the vagi as due to the cutting off of previous inhibitory impulses. But inhibi-
tion in all tissues has a twofold effect. Although the immediate effect is
diminution of activity, yet the diminished disintegration necessarily associated
with diminished activity means an increase of the anabolic at the expense of
the katabolic processes of the tissues. In this way we explained the diminished
excitability occurring in a nerve at the anode of a constant current, and it will

Fig. 198.

Effects of distension— collapse of lung. Both curves are described
by a lever attached to a slip of the diaphragm of a rabbit. A
contraction of the diaphragm (inspiration) raises the lever ; during
relaxation of the diaphragm the lever falls.

In A, the trachea is closed at x, the height of inspiration ; a pause
follows, during which the lever gradually sinks until an inspira-
tion (a very powerful one) sets in.

In B, the trachea is closed at the end of expiration, x ; there follow
powerful inspirations. (From Foster.)

be remembered that the secondary result of anelectrotohus was increased
irritability and consequent excitation at break of the constant current. The
same sort of process must occur in the respiratory centre. A continued
restraint of its rhythmic activity must lead to a heaping up of its irritable
material, so that the final result is a state of hyperexcitability in which the
centre, so to speak, boils over on the slightest provocation.

In this condition a cutting off of the inhibitory impulses must at first
increase the activity of the centre leading to the increased inspiratory tonus
already described. But unchecked by any reining impulses, the centre enters
upon a career of spendthrift activity. Each inspiratory contraction is maximal,
but the centre, exhausted by the effort, has to wait a considerable time before it
can accumulate sufficient energy for the next ; hence the final result of section

RESPIRATION

415

of both vagi is deepening and slowing of respiration. In the normal state we
must imagine that the function of the vagus is to increase the excitability of
the respiratory centre, and so make it more susceptible to slight changes in
the COo tension of the blood.

Although Gad has rendered great service in emphasising the importance of
the inhibitory or expiratory impulses which ascend the vagi, there is no doubt
that he went too far in denying the existence of inspiratory fibres in the vagus.
This is shown by the following experiment of Head. According to Gad's view,
collapse of both lungs implies simply a removal of the normal inhibitory
impulses ascending the vagi, and is therefore equivalent to division of these
two nerves. If in the rabbit the left vagus be divided, a tube can be introduced
into the left bronchus and artificial respiration can be performed by alter-
nate inflation and collapse of the left lung, without in any way affecting the
respiratory centre, all connections with the latter being destroyed {v. Fig. 199).

Fig. 199.

R' Lung.

artif resp app.

L^ Lun

Diagram to illustrate Head's experiment on the effect of collapse
of the lung. E.G., respiratory centre ; E.V., L.V., right and left
vagi.

Meanwhile the animal carries out normal respiratory movements, which can be
recorded by the diaphragm slip method. While the slip is contracting regularly,
the right pleura is opened and the right lung allowed to collapse. The effect of
this collapse carried up by the right vagus to the centre is an extreme contrac-
tion of the diaphragm, and since the onset of asphyxia is prevented by the
artificial respiration carried out on the left lung, the tonic standstill of the
diaphragm may last over a minute. In this case therefore, the effect of collapse
of one lung is enormously greater than that produced by section of both vagi,
showing that the effect is due, not to abolition of the ordinary tonic inhibitory
stimuli, but to excitation of special inspiratory fibres in the vagus by the collapse
of the lunK.

416

PHYSIOLOGY

The important part played by the vagi in the regulation
of normal respiration is shown still more strikingly if the
respiratory centre in the medulla be separated from the higher
parts of the brain before the section of the vagi is carried out.
Separation of the medulla from the higher parts of the brain,
as by a section just behind the corpora quadrigemina, has
practically no influence on the respiratory rhythm. If now
both vagi be divided, the normal respiratory movements cease

Fio. 200.

Different forms of apntta produced by ventilation (Head). A. Normal
tracing of diaj)liragmatic slip ; B. Effect of positive ventilation.
Standstill of diaphragm in complete relaxation ; C. Effect of
negative ventilation. Standstill of diaphragm in a state of tonic
contraction ; D. Effect of combined positive and negative ventila-
tion. Cessation of movements, the diaphragm being in a state of
moderate tone.

entirely, being replaced by a series of inspiratory spasms,
each of which lasts several seconds and is followed by a pause
of half to one minute duration. These spasms are inadequate
for the proper oxygenation of the blood. They become gradu-
ally less and less frequent, and the animal dies in about half
an hour of asphyxia. We must conclude therefore that the
respiratory centre with the help of the vagi is able to carry
out normal respiratory movements. If both vagi are cut,
impulses arrive at the centre from the higher parts of the
brain regulating its activity, and enabling it to carry out
modified but sufficient respiratory movements. Kemoved

EESPIEATION 417

from both these sources of afferent impulses, the centre dis-
charges only a series of spasms which are totally inadequate
for the renewal of the blood gases, so that the animal dies.

We may summarise these results as follows :

Respiratory centre with vagi^normal respiration.

Respirator}^ centre with brain — modified respiration.

Respiratory centre alone — inadequate spasmodic contrac-
tions of respiratory muscles, and death of animal.

Apnoea.—li positive and negative ventilation be used
together, so that air is blown into and sucked out of the
lungs at a rate quicker than the animal's respiratory rhythm,
both inspiratory and expiratory processes are inhibited, and
a standstill of respiration ensues. This condition is called
apnoea. It has been thought to be chiefly reflex in origin, in
consequence of the fact that an apnceic pause may be observed
after artificial respiration for a short time with inert gases,
such as hydrogen or nitrogen. The pause however does not
last so long as when air or oxygen is employed, since in the
former case the blood becomes so venous that the stimulation
of the centre thereby produced overcomes the effects of the
reflex inhibition, and a violent inspiratory movement ensues.

One factor that has not been sufficiently allowed for in
these ventilation experiments is the effect that rapid ventila-
tion with any gas will have in reducing the CO., tension in the
blood circulating round the pulmonary alveoli, and therefore
round the respiratory centre. The respiratory centre has a
specific sensibility to CO.^, while it shares with the rest of the
medulla and cord the susceptibility to absence of oxygen.
Hence any change in the amount of CO, in the air breathed
(irrespective of changes in the oxygen) produces correspond-
ing changes in the respiratory rhythm. If for instance a man
be made to breathe a mixture of oxygen, nitrogen, and CO.^,
containing the ordinary percentage of oxygen (21 per cent.),
but 2 or 3 per cent, of CO^, he experiences a feeling of breath-
lessness, and objectively the respiratory movements are in-
creased in rhythm and extent (hyperpnoea) so as to keep the
COo tension in the alveolar air, and therefore in the blood, at
its normal point. If the CO^ content be increased to about
4-5 per cent., it is impossible to produce an apnoeic pause,
however rapidly the respiratory movements be carried out.
It would seem, therefore, that ordinary apncea is entirely due

27

418 PHYSIOLOGY

to deficiency of CO^ tension in the respiratory centre, and
that I although the vagus nerve is inhibitory of respiration, it
is impossible to summate a series of vagus inhibitions by
artificial respiration so as to produce a lasting cessation of
respiratory movements. The chief use of the vagi, in fact, in
respiration seems to be for maintaining by frequent inhibitions
the excitability of the respiratory centre at a maximum.

"We have seen that if a man breathe a mixture of nitrogen
and oxygen free from CO.,, and the oxygen be gradually
diminished, no feeling of ' want of breath ' may l)e experienced.
Eespiration is often practically unaltered, although the
deficient oxygenation of the blood may be shown by the
blueness of the lips and face. In certain cases great oxygen
deficiency excites the respiratory centre, l)ut in many cases
no ill effects may be felt by the subject before he suddenly
becomes unconscious from lack of oxygen. Immediately
following this loss of consciousness may come the convulsive
phenomenon of asphyxia.

From the lack of any mechanism in the respiratory
centre to respond to minute changes in the oxygen tension of
the surrounding atmosphere, it follows that any diminution
in oxygen tension (as by change of altitude) must cause a
corresponding diminution in the degree of saturation of the
haemoglobin of the blood with oxygen. This change in
oxygen saturation is at once felt by the blood-forming organs ;
so that a change of habitation from a low-lying to a mountain
district is followed by an increased production of blood cor-
puscles, until the oxygen carrying capacity of the blood is the
same at the lower oxygen tension as it was previously at the
higher oxygen tension of the plains.

Broncho-motor functions of the vagus.— -The unstriated muscular fibres,
which form a prominent element in the walls of the bronchioles, receive fibres
from the vagi which are efferent in function. If positive ventilation under a
constant pressure be maintained in an animal and the excursions of the chest-
wall recorded, a perfectly regular series of movements are obtained, which serve
as a measure of the expansion of the lungs under each inspiratory blast of air.
If now the peripheral ends of both vagi be stimulated, the excursions of the
lever at once are diminished in extent, showing that the air does not enter and
expand the lungs with its former freedom. The vagi in fact are the motor
nerves to the bronchial muscle. Stimulation of these nerves therefore causes
occlusion of the smaller air-tubes and diminished entry of air into the lungs.
The attacks of dyspnoea which characterise asthma are due to spasmodic con-
traction of the bronchial muscle, probably in consequence of abnormal stimula-
tion of the central origin of the vagi.

EESPIRATION 419

Cha7iges in Composition of Air breathed

The oxygen tension of the air can be considerably reduced
without causing inconvenience. If however a mammal be
exposed to air at a pressure of 300 mm. (corresponding to a
partial oxygen pressure of GO mm. Hg), it becomes dyspna-ic
and dies of asphyxia. The experience obtained in balloon
and mountain ascents is in complete harmony with the result
of this experiment. Dyspncea does not begin till a height of
5,000 metres is reached, which corresponds to a mercurial
pressure of 400 mm. Hg.

It is interestmg however to note that the extreme dyspnoea
with which mountaineers are attacked at a height of about
5,000 metres passes off after some time, and then they may
pursue their way another 1,000 metres higher without any
discomfort (Whymper). In view of the results given on
p. 394, it seems at first diiKcult to explain the deleterious
effects of high altitudes or reduced oxygen pressures. It was
there mentioned that even at a partial pressure of oxygen
of 25 mm. Hg (corresponding to an atmospheric pressure of
119*3 mm. Hg, or to a height above the sea of about 14,000
metres), as much as 73*3 per cent, of the haemoglobin was con-
verted into oxyhaemoglobin, and yet dyspncea is produced at a
height of 6,000 metres, corresponding to a pressure of 358 mm.
(75 mm. oxygen). We must remember however that an
important factor in the respiratory exchanges is the rapiditij
of passage of oxygen from air to blood. The blood is con-
stantly circulating through the lungs, and during the short
time of its passage becomes nearly saturated with oxygen.
The velocity of passage of oxygen across the epithelial
membrane will vary directly as the difference of pressure on
the two sides of the membrane. As this difference diminishes,
the organism seeks to increase the velocity of passage by
increasing the area of lung surface, i.e. by deepening of the
respiratory movements. At the same time there is quicken-
ing of the heart's action and increased velocity of blood-flow
so as to increase the amount of oxygen carried by the blood
in a given time. These processes of compensation however
cannot go on indefinitely, and distress, which is chiefly cir-
culatory in character, begins to be experienced when the limit
of compensation is arrived at. This limit occurs in trained men

420 PHYSIOLOGY

at an atmospheric pressure of about 400 mm. Hg ; and it is
of course reached sooner if the respiratory needs of the
organism are increased by severe muscular exercise (as in
mountain climbing). The gradual accustoming to heights,
which is a common experience, is a complex phenomenon,
due partly to training of respiratory and heart muscles, and
partly to an increase of red corpuscles and haemoglobin con-
tents of the blood. It is probable that the dwellers in mountain
regions, such as the lofty South American plateaus of Potosi,
Quito, etc., would be found to have a greater lung area per
unit body weight than the dwellers on the plains.

If the oxygen in the air supplied to an animal be reduced
to 3 per cent., it rapidly dies of asphyxia with convulsions.
Excess of carbon dioxide also proves fatal, but in a different
manner. If an animal be placed in an atmosphere contain-
ing 6 per cent, of CO^, after a stage of hyperpncea it gradu-
ally becomes narcotised and dies without convulsions. CO., is
therefore looked upon as a narcotic poison.

Gases such as nitrogen, hydrogen, and methane (CH^)
are termed indifferent gases. They may be respired if mixed
with 20 per cent, of oxygen, and either of the other gases
may be used instead of nitrogen to dilute the oxygen that we
breathe, without harm or inconvenience.

Carbon monoxide is rapidly poisonous by its action on the
red corpuscles. It combines with haemoglobin, forming CO
haemoglobin, a compound which is much more stable than
oxyhaemoglobin. The blood is therefore deprived of its
oxygen carrier, and the animal dies of asphyxia. We have
seen however that the displacement of oxygen by CO is not
absolute, but only relative. Hence, although the avidity of
CO for haemoglobin is 140 times that of oxygen, we can
convert the CO back into oxyhaemoglobin by increasing the
mass influence of the oxygen. This may be done by giving
the poisoned animal pure oxygen to breathe, or even oxygen
under pressure. In pure oxygen at a pressure of two atmo-
spheres an animal can breathe and live, even though the
whole of its haemoglobin is converted into CO haemoglobin,
the amount of oxygen which is simply dissolved by the blood -
plasma being sufficient at this pressure for the respiratory
needs of the animal.

Other gases which have special poisonous properties are

RESPIRATION 421

hydrocyanic acid, sulphuretted hydrogen, phosphuretted
hydrogen (PH3), arseniuretted hydrogen, etc.

Irrespirahle gases are those which are so irritating that
they produce spasm of the glottis. Such are ammonia,
chlorine, sulphur dioxide, nitric oxide, and many others.

Ventilation

A point of practical importance is the securing to each
individual of sufticient fresh air, so that he may always have
a plentiful supply of oxygen, and may be relieved of his
waste products. It is found that a dwelling-room becomes
unpleasant and stuffy when the percentage amount of CO^
has reached 0-1 per cent. This stuffiness is supposed to be
due to organic exhalations from the skin, lungs, and alimen-
tary canal, some of which have a poisonous effect, giving rise
to headache and sleepiness. Since these cannot be measured,
it is taken as a cardinal rule in ventilation that the amount
of CO,, should never rise above 0*1 per cent. An adult man
gives oft' about 0*6 cubic foot of CO2 every hour. Hence in
that time he raises the amount of CO., in 1,000 cubic feet of
air from 0*04 per cent, (the normal amount in the atmosphere)
to 0-1 per cent. He must therefore be supplied with 2,000
cubic feet of air per hour in order to keep the amount of CO.,
down to 0-07 per cent.

(Ordinary air contains 0'04 per cent. CO.,, therefore 2,000
cubic feet would contain 0*8 cubic foot CO.^, which with the
0*6 cubic foot given off by the man would be 1-4, which is
0-07 per cent.)

In order that the air may be easily renewed without
giving rise to excessive draught, a certain amount of cubic
space must be allotted to each man. Each adult should have
in a room 1,000 cubic feet of space, and be supplied every
hour with 2,000 to 3,000 cubic feet of air.

422 PHYSIOLOGY

Section 4

EFFECTS OF THE EESPIEATORY MOVEMENTS ON
THE CIECULATION

The Pulmonary Circulation

Although the maintenance of the ch'culation through the
lungs is the sole function of the right side of the heart, and
so is of equal importance with the whole systemic circulation,
yet owing to the simple features of this circulation it can be
dealt with in a very short space. In the lungs we have an
extensive system of wide capillaries presenting very little
resistance to the flow of blood. The arterioles are also wide
and have only a slight amount of muscular fibre in their walls,
and we find therefore that the pressure necessary to drive the
blood from right to left heart is also small. The determina-
tion of the normal average pressure in the pulmonary artery
presents considerable difficulties, but it probably does not
exceed 25 mm. Hg, i.e. about one-sixth of the mean aortic
pressure.

The capillaries of the lungs may vary passively consider-
ably in size according to the conditions under which they may
be placed. Thus whereas at ihe height of inspiration the
blood contained in the lungs is about y^ o^ the whole blood
in the body, this amount is diminished during expiration to
between -^K^ and y^-, and by forcible artificial inflation of the
lungs may be lessened to ^. These changes, as we shall see
later, exercise a considerable effect on the systemic blood-
pressure and are largely responsible for the respiratory varia-
tions observed in the systemic blood-pressure.

On the other hand this distensibility of the lung capillaries
may play an important part in enabling the lungs to act so to
speak as a reservoir for the left side of the heart. Any tem-
porary excess of output on the right side that, in consequence
of raised arterial pressure or other factor, cannot be dealt
with at once by the left heart, is taken up for a time in the
lung capillaries.

Vaso-motor fibres to the lung vessels have been described

EESPIRATION

423

as running in the anterior roots of the 3rd, 4th, and 5th dorsal
nerves. Their action is however of little importance.

The Bespiratory Undulations in the Systemic Blood
Br ess lire

If we examine a tracing of the arterial blood-pressure,
we notice that it presents certain periodic oscillations which
accompany the movements of respiration. With each inspira-
tion the blood-pressure rises ; with each expiration it falls.
The synchronism of the rise and fall with the respiratory
movements is not exact, since the rise continues for a short
time after the beginning of expiration, before it begins to fall,
and the fall continues right into the beginning of the next
inspiration, so that the highest pomt of the curve occurs at the
beginning of expiration and the lov>'est point at the beginning
of inspiration. During the fall which accompanies expira-
tion, the heart-beats, as shown in the diagram (Fig. 201),

Fig. 201.

Bespiratoiy (racuiff.

Diagram of blood-pressure curve, showing effects of the respiratory
movements on blood-pressure and pulse-rate.

become less frequent, and an obvious explanation of the fall
of pressure would be to ascribe it to a reflex inhibition of the
heart. On dividing both vagi, this difference in the pulse-
rate during inspiration and expiration disappears, but the
main features of the blood-pressure curve remam the same ;
so that we must look for some mechanical explanation of the
respiratory undulations.

We have already seen that under normal conditions the
lungs are in a state of over-distension, and that in consequence
of this condition they are constantly tending to collapse, and
are therefore exerting a pull on the chest-wall. As soon as

424 PHYSIOLOGY

we admit air into the pleural cavity by perforating the chest-
wall, the lungs collapse. The force with which the lungs are
normally trying to collapse amounts to 6 mm. Hg, so we
say that in the pleural cavity there is normally a negative
pressure of — 6 mm. Hg.

As the chest expands in inspiration, it drags the lungs still
more open. As these become more distended, their tendency
to collapse becomes greater, and hence the negative pressure
in the pleura may be increased during forcible inspiration to
— 30 mm. Hg.

It must be remembered that the heart and great veins and
arteries are in the thorax only separated from the pleural
cavity by a thin, yielding membrane, so that they are practi-
cally exposed to any pressure, positive or negative, which may
exist in the pleural cavity.

Hence even at the end of expiration the heart and large
vessels are subjected to a negative pressure of ~6 mm. Hg.
Outside the thorax all the vessels are exposed to a positive
pressure, conditioned in the neck by the elasticity of the
tissues, and in the abdomen by the contractions of the dia-
phragm and abdominal muscles.

Now blood, like any other fluid, will always flow from a
point of higher to a point of lower pressure. There must
thus be a constant aspiration of blood from peripheral parts
into the thorax. This aspiratory force will however not
influence arteries and veins alike. The arteries, having thick
comparatively non-distensible walls, will be very little affected
by the negative pressure obtaining in the thoracic cavity,
whereas the thin-walled distensible veins will be very largely
influenced by the same factor. The total result then of the
negative pressure in the pleural cavities is to increase the
flow of blood from the veins into the heart, without afl"ecting
to any appreciable degree the outflow of blood from the heart
into the arteries. The more pronounced the negative pres-
sure in the thorax, the greater will be the amount of blood
sucked into the heart from the veins. During inspiration
therefore, the heart will be better supplied with blood than
during expiration, and this factor in itself will tend to raise
the arterial blood- pressure.

The mspiratory descent of the diaphragm will moreover
tend to increase the inflow into the heart by raising the

KESPIRATION 425

positive pressure in the abdomen, so that blood is jiressed out
of the abdominal veins and sucked into the heart and thoracic
veins.

Still more important is the influence of the respiratory
movements on the circulation through the lungs. In trying
to understand this influence, it must be remembered that the
pulmonary capillaries lie in a certain amount of elastic and
connective tissue, and are separated on the one side by the
alveolar epithelium from air at the ordinary atmospheric
pressure, and on the other by the pleural endothelium from
the pleural cavity, where the pressure varies from 6 to
30 mm. Hg below the atmospheric pressure. We may there-
fore consider the pulmonary capillaries as lying between,
and attached to, two concentric elastic bags, as represented
in Fig. 202. Under normal conditions, since these bags are
always tendmg to collapse, the inner one must be pulling
away from the outer one, and the outer one from the chest-
wall. Hence there must be a negative pressure in the
tissues between these two bags — a negative pressure which in
the expiratory condition will be something between 0 and

— 6 mm. Hg, and in the inspiratory condition between 0 and

— 30 mm. Hg. If we regard the average pressure within
the pulmonary capillaries as constant, these capillaries must
be more dilated in the inspiratory than in the expiratory
condition, as shown in the diagram (Fig. 203). Now this
dilatation of the pulmonary capillaries will have two effects.
Their capacity will be increased and the resistance they
present to the flow of blood will be diminished.

Let us now consider what effect these changes will have
on the general arterial blood-pressure. We will assume that
during expiration (Fig. 202) the pulmonary vessels have a
capacity of 25 c.c, and that the beat of the right heart is
forcing through them 10 c.c. of blood per second. So long as
the chest remains in the expiratory condition, 10 c.c. of blood
will be flowing into the left heart and into the aorta, so that
the sj^stemic blood-pressure will remain constant. Now let
us suppose that an inspiratory enlargement of the thorax
takes place (Fig. 203). The negative pressure in the pleura
is increased, the two walls of the lung are pulled farther away
from one another, and there is a general enlargement of the
pulmonary capillaries. We will assume that this enlarge-

426

PHYSIOLOGY

ment increases the capacity of the pulmonary capillaries from
25 to 30 c.c. Owing to this increased capacity, the first 5 c.c.
of blood, which flows into the kings after the beginning of
inspiration, will not flow out through the pulmonary vein, but

Fig. 202.

Mariometes

Diagram to show condition of pulmonary vessels in expiration.

will simply serve to bring the capillaries into the same state
of distension as before. Hence at the beginning of inspiration
the flow through the pulmonary vein will be diminished ;
there will be less blood discharged into the left heart, and

Fig. 203.

^&^\

II

Manomefer
connected

with
I'leuw.lCaviti/

■ Pulm. Veiiv.
Pulmonary
Artertf.

Diagram to show condition of pulmonary vessels in inspiration.

therefore a fall in systemic pressure. As soon however as the
increased capacity of the pulmonary vessels is made up, the
dilating effect of the inspiratory movement of these vessels
will aid the flow through the lungs, in consequence of the
diminution of resistance, so that the same force of the right

RESPIRATION 427

heart, which drove 10 c.c. of blood per second through the
former resistance during expiration, will now drive more, say
12 c.c. of blood. There is thus more blood entering the left
heart, and therefore a rise of systemic pressure during the
last three quarters of the inspiratory movement.

Expiration will have exactly the reverse effect. At the
beginning of expiration there is a diminution of capacity in
the pulmonary vessels from 30 to 25 c.c. Hence during the
first second of expiration the outflow of blood from the
pulmonary vein into the left heart will be 17 c.c. (12 c.c. +
5 c.c). After this, the increased resistance in the pulmonary
capillaries in consequence of their constriction will come
into play, and the flow of blood through them will fall once
more from 12 c.c. to 10 c.c. Hence at the beginning of expira-
tion the inflow of blood from the pulmonary vein into the left
heart is greater than at any period. The arterial pressure
will therefore rise to its greatest height at the beginning
of expiration, and will fall during the last three quarters of
expiration, but will attain its minimum only at the beginning
of the next inspiration.

In this way the effect of the respiratory movements on
the systemic blood -pressure can be entirely explained by the
influence they exert on the lung vessels or lesser circulation.

428

PHYSIOLOGY

Section 5
VOICE AND SPEECH

Voice. —The voice is produced by an expiratory blast of
air being forced through the narrow interval between the
true vocal cords. These, which are thin, membranous, and
elastic, are set into vibration by the current of air, and the

Fk;. 204.

Anterior half of the larynx, seen from behind. The section on the
right side is somewhat in front of the left side, e, epiglottis ;
c', cushion of epiglottis ; t, thyroid cartilage ; s, s', ventricle
of larynx ; h, great cornu of hyoid bone ; t a, thyro-arytaenoid
muscle ; v I, vocal cords. Above the ventricles are the false vocal
cords, r, first ring of trachea. (A. Thomson.)

vibrations are communicated in turn to the air in the upper
air-passages. The pitch of the sound produced depends on
the rapidity of vibration of the vocal cords.

The vocal cords are composed of elastic and muscular fibres, covered over
by mucous membrane, and running from the anterior processes of the arytse-
noid cartilages behind to the posterior surface of the angle of the thyroid

RESPIEATION

429

cartilage in front. The arytsenoicl cartilages are small pyramidal masses of
fibro-eartilage resting on the back part of a ring-shaped cartilage, the cricoid
cartilage. This is thin in front, but thick behind, being produced upwards at
its back part for the attachment of the arytaenoids.

The thyroid cartilage consists of two wings or alae, articulated to the sides
of the cricoid, so that the back part of the cricoid can move backwards and
forwards.

These four cartilages form the skeleton of the larynx. By their relative
positions the tension of the vocal cords and the shape of the rima glottidis
are determined. These movements are carried out by the following muscles :

The crico-thyroid muscle passes downwards and forwards from the lower
part of the thyroid cartilage to the front part of the cricoid.

The loosteriar crico-arytcEnoid muscle arises from the posterior surface of
the cricoid cartilage and is inserted into the outer angle of the arytsenoid
cartilage.

Fig. 205. Fig. 20G.

^— - c.a.p

Fig. 206.— Side view of cartilages of larynx, th, thyroid cartilage ;

ar, arytsenoid cartilage ; cr, cricoid cartilage ; ctm, crico-thyroid

muscle ; cli, vocal cords.
Fig. 207.— Back view of larynx, ar.m. arytsenoid muscle with the

oblique fibres which pass round to join the arytseno-epiglottidean

muscles ; ca-p. posterior crico-arytsenoid muscles.

The lateral crico-arytcenoid runs upwards and backwards from the middle
third of the upper border of the cricoid cartilage to the anterior margin of the
base of the arytsenoid cartilage.

The arytcenoid is a single flat muscle running horizontally between the
posterior borders of the two arytsenoid cartilages.

The thyro-arytanoid muscles run from the internal surface of the thyroid
cartilage, close to the angle, backwards, to be inserted into the lateral
border of the arytsenoid cartilage, the most internal fibres being contained
in the vocal cords, and inserted into the processus vccalis of the arytsenoid.

The false vocal cords are two ridges of mucous membrane, lying over and
parallel to the true vocal cords, and separated from them by a lateral recess
known as the ventricle of the larynx.

During ordinary respiration the glottis or opening between
the vocal cords remains about half open, being rhythmically
widened with every inspiration. For the production of voice,
the free borders of the vocal cords must be brought so near

430 PHYSIOLOGY

to one another that they almost touch, and a narrow chhik
with parallel sides is formed. At the same time they must
be more or less tense, according to the pitch of the note to
be produced. Both these changes are effected by the agency
of muscles, the narrowing of the glottis by the contraction
of the lateral crico-arytsenoid muscles acting in conjunction
with the posterior arytenoid and the external thyro-arytse-
noid muscles. The tightening is brought about by the con-
traction of the crico-thyroid. This muscle raises the anterior
part of the cricoid cartilage so that its upper part, to which
the arytaenoids are attached, is carried backwards, and thus
the vocal cords are put on the stretch. At the same time
the tension may be regulated by the contraction of the
internal thyro-aryt?enoid muscles.

The pitch of the tone depends on — ■

1. The length of the vocal cords. It is well known that
the pitch of a stretched string varies inversely as its length.
A piece of catgut one foot long will, on being struck, give a
note an octave higher than a similar piece two feet long, if
both are under the same tension. Comparative measurements
show that the vocal cords of men are one and a half times
the length of those of women, and this explains the difference
in the pitch of their voices. Among men those with a tenor
voice have shorter vocal cords than those with a bass one.

2. Tension of the vocal cords, which is modulated by the
degree of contraction of the crico-thyroid muscle.

The intensity or loudness of the voice depends on the
strength of the expiratory blast of air, since the more
powerful this the greater the amplitude of the vibrations of
the vocal cords produced.

The changes in the glottis accompanying phonation are best studied with
the aid of the laryngoscope. This consists essentially of two mirrors ; the
larger, which has a small hole in the middle, is fastened on to a spectacle
frame, which the observer wears. This mirror is used to reflect a powerful
Ijo-ht into the back of the pharynx of the person to be observed. A small
round mirror about half an inch in diameter, mounted on a handle, is then
introduced into the pharynx until it is directly over the opening of the larynx.
The observer then sees in the small mirror a reflected image of the epiglottis
and arytseno-epiglottidean folds, with the true and false vocal cords lying
between them.

The human voice extends to about 3i octaves, although
it is rare to find any individual compass extending over two

RESPIKATION 431

octaves. In men two kinds of voice can be distinguished —
the chest register and the head register or falsetto. In the
latter form of voice it is said that the vocal cords are wider
apart, and that only their innermost margins are set into
vibration by the current of air.

Speech. — Articulate speech is produced, not in the larynx,
but in the mouth and pharynx. If these parts alone are
called into play, the expiratory blast of air is so modified as
to give rise to whispering speech ; if at the same time there
is a production of voice in the larynx, ordinary speech is
the result.

The sounds that take their origin in this way are divided
into vowel sounds and consonants.

The voivels a, e, i, o, u (pronounced ah, eh, ee, o, oo) are
tones, i.e. are produced by a regular series of vibrations.

The special characters of each vowel sound were shown
by Helmholtz to be due to the combination of overtones,
which is different for each vowel. This was determined in
the following way : —A person was made to tone the vowel
sounds on one particular note, and by means of resonators
the component vibrations of each vowel sound were analysed.
These being fomid, the experiment was completed by reform-
ing the vowel soimds synthetically by means of tunmg-forks
arranged to vibrate at the same notes as the notes of the
resonators that picked out the sounds in the first experi-
ment.

Thus if h be taken for the fundamental tone,

b + b, = u(ooj.

b + b, (loud) + f, (soft) = 0.

b + b, and f^ (moderately loud), f, (louder), l^, Rj and bj (loud) = e (eh).

i = ee could not be reproduced, since its higher overtones
could not be artificially represented by means of tuning-
forks.

The difference in the overtones accompanying the fun-
damental tone, and therefore in the vowel soimds, is brought
about by changes in the shape of the cavity of the mouth
and pharynx (Fig. 207). When o and ou are sounded, the
mouth-cavity has the shape of a flask without a neck, the
opening being situated at the mouth. The opening is narrow
when 00 is sounded, wider with o.

432

PHYSIOLOGY

When a {ah) is sounded, the mouth-cavity assumes a wide
conical form, the widest part of the cone being at the mouth.
With e {eh) and i {ee) the cavity assumes the form of a flask
with a long narrow neck which is formed by the raising of
the tongue, leaving a narrow canal between this organ and
the hard palate.

These changes can be observed roughly by any one on
himself if he intones oo, and then gradually changes the
sound to 0, ah, e, i, directing close attention to the changes
that he is making in his mouth.

The vowel sounds, we may conclude, are brought about by
variations in the shape of the cavity of the mouth and pharynx,
which alter the quality of the tone produced in the larynx

Fi«. 207.

A (ah) U (oo) I (ce)

Shape of the oral cavity in the production of the vowel sounds, A, U, 1
(Griitzner).

by intensifying some and suppressing other harmonics or
overtones.

Diphthongs are produced by changing the form of the
mouth-cavity from that of one vowel-sound to the other,
so that one sound follows directly after the other ; thus
ai = ah-ee run together and abbreviated. Consonants are
sounds produced by a sudden check being placed in the
course of the expiratory blast of air by closure of some part
of the pharynx or mouth. They are classified into labials,
dentals, or gutturals, according as the check takes place at
the lips, between teeth and tongue, or between back of tongue
and soft palate.

In the production of nasal sounds, such as m, n, or ng,

RESPIKATION 433

the mechanism is the same as for the production of h, d, and
g, except that the posterior opening of the nares is not
kept shut by the soft palate, so that part of the sound comes
continually through the nasal passages, when it acquires
a peculiar resonance. These sounds are on this account
often spoken of as resonants. The aspirates are produced
by the passage of a simple blast of air through a narrow
opening which may be at the throat as in li, between
tongue and teeth as in tli, or between lips and teeth as in
ph or /.

28

434 PHYSIOLOGY

CHAPTER X
EXCRETION— FUNCTIONS OF THE KIDNEYS AND SKIN

Section 1

THE UEINAEY CONSTITUENTS AND THEIR OEIGIN
IN THE BODY

The consideration of the lungs, which are organs engaged
at the same time in absorption and excretion, leads us on
naturally to those organs by which the remaining waste
products of the organisms are eliminated, i.e. the kidneys
and skin.

The main work of the kidneys is the excretion of urea,
the product of the nitrogenous waste of the hodj. This is
turned out dissolved in water, together with certain other
nitrogenous extractives, salts, and water, which together make
up the urine.

Human urine in a fresh condition is a clear yellow fluid,
with characteristic odour and sour reaction. Its specific
gravity is on the average 1016 — 1020. It is free from
organised elements. An average man of 66 kilos weight
passes in twenty-four hours about 1,500 grms. of urine.
This contains about 73 grms. of solids, which are made up
as follows :

Urea 33 grms.

Uric acid ....... 0'5 „

Hippuric acid 0*4 ,,

Creatinine . 0'9 „

Pigment and other substances . . . 10 „

Sulphuric acid 2 ,,

Phosphoric acid 3 ,,

Chlorine 7 „

Potassium 25 „

Sodium ....... 11 „

Ammonia 0*7 „

Calcium )

Magnesium 1 "

FUNCTIONS OF THE KIDNEYS AND SKiN 435

It also contains about 15 volumes per cent, of gas,
consisting chiefly of carbon dioxide, with a small amount of
nitrogen.

The acidity of the urine is due to the presence of acid
sodium phosphate, and is equivalent to about 2 grms. of
oxalic acid in twenty-four hours. While active digestion is
going on, the urine may be for a while alkaline, owing to the
secretion of hydrochloric acid by the stomach. The reaction
varies with the nature of the food. In herbivora the urine
is normally alkaline, becoming acid only when they have had
no food. In this condition their metabolism is going on at
the expense of their own bodies, so that they may be regarded
as carnivorous for the time being. The acidity of the urine
diminishes on standing, and if the fluid be exposed to the air,
a development of micro-organisms {Micrococcus urecB) takes
place. By their agency the urea is combined with two mole-
cules of water to form ammonium carbonate, and the urine
becomes strongly alkaline and ammoniacal.

Urea

Of these constituents, urea or carbamide is by far the
most important, since the greater bulk of the nitrogen
produced by the disintegration of proteins leaves the body
in the form of urea.

It may be prepared from urine in the following way : — The urine is evapo-
rated to a small bulk (^), and strong pure nitric acid is added in excess,
keeping the mixture cool. Crystals of urea nitrate are deposited. These
are collected and dried between filter-paper, and made into a paste with a
large quantity of barium carbonate and spirit. The paste is dried in a
water-bath and extracted with alcohol. The alcoholic extract is filtered off
and allowed to evaporate, when crystals of urea separate out. These may be
redissolved, decolorised by animal charcoal, and allowed to crystallise out once
more.

Urea crystallises in four-sided prisms. It is odourless
and colourless, readily soluble in alcohol and water. With
nitric acid it forms nitrate of urea, which crystallises in
octahedra (Fig. 208). It also forms typical insoluble crystals
with oxalic acid (Fig. 209).

On heatmg it melts and decomposes, giving oft" ammonia
and forming biuret.

436

PHYSIOLOGY

The reaction may be represented as follows

/NH.,

\nh.,

CO

/

NH.,

CO

\nh
\nh.

On further heating cyanuric acid C3H3N3O3 is formed.

Urea may be formed from ammonium cyanate, with which
it is isomeric, by simply heating with water.

On exposure to the air urine becomes strongly alkaline,
and smells of ammonia. At the same time the earthy phos-
phates are precipitated. This change (which may be prevented
by boiling the urine in a flask, the neck of which is closed
by cotton wool) is due to infection of the urine by a micro-
organism, Micrococcus urecB. Under the influence of this

Fig. 209.

Urea nitrate.

Urea oxalate.

organism the urea undergoes hydration, taking up two mole-
cules of water and being converted into ammonium carbonate.

/NH., /ONH^

CO; "+2H„o = coC

\NH,

Urea

\onh/

Ammoniuui carbonate

On treatment with an alkaline hypobromite it is de-
composed with the formation of free nitrogen and carbon
dioxide :

CO(NH.,).,-H3NaBrO = C0, + N, + 3NaBr 4-2H,0.

This reaction is taken advantage of in the quantitative
estimation of urea. 5 c.c. of urine are treated in a closed
vessel with about 20 c.c. of alkaline sodium hypobromite
solution. The CO2 produced is dissolved by the excess of alkali
present, and the nitrogen is collected in a graduated cylinder

FUNCTIONS OF THE KIDNEYS AND SKIN 437

over water. From the amount of nitrogen given off, the
amomit of urea present in the urine may be calculated.
35'4 c.c. of nitrogen correspond to 1 decigram of urea.

Since urea is the end-product of the metabolism of the
proteins taken in with the food, whether these have been
built up to form constituent parts of the living cells of the
organism or have been broken down at once on their entry
into the body, the amount of it excreted in the day is an
index to the activity of the protein metabolism. Hence it is
increased by a large protein diet ; as well as under conditions
such as fevers, when a rapid disintegration of the tissues
is going on. It is moreover increased by administration of
nitrogenous extractives, such as glycine or leucine, or of
combinations of ammonia with carbon dioxide or vegetable
acids, or of large quantities of water.

Origin of Urea

Urea is not formed in the kidneys. If the kidneys of an
animal be extirpated, urea accumulates in all the tissues and
organs of the body, in which it is found at death in large
quantities. Circulating blood constantly contains a small
proportion of urea, and the kidney-cells merely take up this
urea and turn it out into the urinary tubule. So we have to
inquire what are the immediate precursors of urea, and in
what organ or organs their transmutation into this body is
effected.

Some clue in our investigation of this question is furnished
by the results obtained in the experiments on the disintegra-
tion of proteins described in Chapter II. We saw there that
a protein, on hydrolytic dissociation, broke up into a large
number of bodies, belonging to the following classes :

1. Amino-acids, such as leucine, tyrosine, aspartic and
glutamic acids.

2. Ammonia.

3. Diamino-acids and bases, such as lysine, arginine, and
histidine.

We have to inquire whether any of these or allied sub-
stances occur as stages in the normal metabolic processes of
the body and by what chemical processes they are converted
into the end-product, urea. In the case of one of these

438 PHYSIOLOGY

bodies, arginine, the derivation of urea is extremely simple,

since mere boiling with baryta water serves to split off part

of the molecule in the form of urea, according to the following

equation :

NH. NH,,.

V(C5H„N„0.,) + H.,0 = >C0 + C3H„(NH,),p..

NH./ ■ " ' NH,/

Arsriuine "IJrea Diaiiuno-vnleriaiiic acid

This mode of origin will however account at the most
only for one-ninth of the total protein. The other eight-
ninths of the urea must be obtained from the other decom-
position products, especially from the amino-acids. Amino-
acids are known to be formed in the intestine in the
pancreatic digestion of proteins, and are also formed in the
ordinary metabolic processes of the body. We may instance
glycine and taurine, which are manufactured by the liver
and are combined with cholalic acid to form the bile acids.
It is impossible however to conceive chemically the direct
conversion of these amino-acids into urea. These bodies all
contain a much larger proportion of carbon to nitrogen than
does urea, and we must therefore assume that the first stage
in the change is one of oxidation. The carbon-holding part
of the molecule is oxidised to CO,, and part of this CO^
unites with the ammonia of the amino-radical to form
ammonium carbonate, from which, by a simple process of
dehydration, carbamide or urea may be formed.

CH.,.NH., /O.NH,

(1) 2 I " ' + 30., = C0( + SCO., + H.O.

CO.OH ' \O.NH,

Glycine Amuioiiinni carbonate

/O.NHj /NH.,

(2) C0( - 2H.,0 = C0(

\O.NH^ " ^NH,

Carbamide oi' area

If ammonium carbonate be administered to an animal, no
increase is found in the ammonia of the urine, but a large
increase in the urea, showing that the ammonium carbonate
has been converted into urea.

Where does this conversion take place ?

If defibrinated blood mixed with ammonium carbonate be
passed through the blood-vessels of a recently excised-mam-
pialian liver, the urea in the blood is found to be increased
200 or 300 per cent., and there is a corresponding decrease

FUNCTIONS OF THE KIDNEYS AND SKIN 439

in the amount of ammonium carbonate in the blood. The
same result, viz. a formation of urea, is obtained if amino-
acids, such as leucine or glycine, be added to the blood that is
perfused through the liver. We see therefore that the liver
has the power of carrying out the series of oxidations and
dehydrations described in the previous paragraphs, which
result in the formation of urea.

Many experimental facts point to the conclusion that this
power is normally exercised during life, and is indeed one of
the chief functions of the liver. Comparative analyses of the
blood of the portal vein and of the carotid artery or hepatic
vein show a marked difference in the ammonia content of the
blood. Whereas carotid blood contains only 2-3 mg. of NH3
in 100 c.c, portal blood contains 4-6 or during digestion
even 8 mg. per 100 c.c. If by any means the proportion of
ammonia in carotid blood is raised to that in portal blood,
the animal shows symptoms of poisoning, being affected
with convulsions or coma, which may end in death. The
liver therefore is constantly engaged in removing ammonia
from the blood and converting it into an innocuous sub-
stance (urea).

The decisive experiment of extirpation of the liver pre-
sents in mammals considerable difficulties. Since all the
blood from the alimentary canal passes through the liver,
extirpation of this organ involves enormous venous conges-
tion of all the portal area. The wall of the intestines
becomes thickened and black from effused blood, the blood
in the general circulation becomes concentrated and the
animal dies within a few hours. It is evident that this
difficulty might be overcome if we could in any way make
an opening between the portal vein and inferior vena cava,
so that the liver might be excised without interfering with
the circulation through the gut. This difficult operation
has been carried out by Pawlow, though previously suggested
by Eck, a Kussian surgeon. In a number of animals in
which this operation had been performed, the portal vein
was ligatured so that the liver was supplied with blood only
through the hepatic artery. In this case the portal blood
had to pass through the general circulation before arriving
at the liver, and it was therefore found that any increase of
nitrogenous metabolism, such as that caused by a protein

440 PHYSIOLOGY

meal, brought about symptoms of ammonia>Ania, the convul-
sions and coma mentioned above. On a farinaceous diet, the
animals (dogs) could be kept alive a considerable time, and it
was observed that the dogs themselves soon recognised the
evil effects of a meat diet and changed their tastes in conse-
quence. In animals suffering from these symptoms, the urea
in the urine was somewhat diminished, its place being taken
by ammonia. A large proportion of this substance was
present in the form of ammonium carbamate. This fact
points to the possibility that the combination of ammonia
and carbon dioxide in the tissues results in the formation
of this salt rather than of the carbonate, and that the
ammonium carbamate is therefore the immediate precursor
of urea. In dogs with an Eck's fistula and the portal vein
ligatured, obstruction of the hepatic artery brings about
death within twelve to twenty-four hours. During this time
a small amount of urine may be secreted, containing a fair
proportion of urea, a fact which has been interpreted as
showing that other tissues besides the liver take part in the
formation of urea.

The importance of the liver for the transformation of the
amino-acids is illustrated by the fact that in acute yellow
atrophy of the liver, as well as in the similar condition
brought about by the administration of phosphorus, the
urea may disappear from the urine, its place being taken by
leucine, tyrosine, and other amino-acids, as well as ammonia.

Confirmatory evidence on this subject is furnished by
experiments on birds. In this class there is no need to per-
form Eck's fistula, since there is normally a communication
(the vein of Jacobson) between the portal vein and the renal
veins, and so with the vena cava (Fig. 210). Hence they
may survive the operation of extirpation of the liver for
several days, during which time the kidneys continue to
perform their normal functions. Unfortunately for our
present question, in birds the greater part of the nitrogen
is excreted as uric acid, and not as urea. Extirpation of the
liver causes an almost total disappearance of the uric acid
in the urine, and a corresponding appearance of ammonia.
In healthy geese, for instance, the nitrogen eliminated as
uric acid amounts to from 60 to 70 per cent., and as
ammonia to from 9 to 18 per cent, of the total nitrogen.

FUNCTIONS OF THE KIDNEYS AND SKIN

441

After removal of the liver the uric acid nitrogen represents
only 3 to 6 per cent., and the ammonia 50 to 60 per cent.
These figures show clearly that in birds ammonia is a pre-
cursor of uric acid, and that the presence of the liver is
essential for its conversion into this substance.

It is interesting to notice that under such conditions a
large quantity of lactic acid occurs in the urine combined
with the ammonia as ammonium lactate — a fact not without
significance in view of the artificial synthesis of uric acid
from trichlorlactic acid and urea.

Iliac vein-
Kidney

Fig. 210.
Inf. Vena Cava

V. of Jacobson
Inf. mes. V.

Caudal v. —

Poctal V.

Diagram to show the arrangement of the veins in the bird, with
the communication of the renal and portal veins. (After
Morat.)

Another important precursor of urea is represented by
creatine. This nitrogenous substance occurs in the organism
in far larger quantities than any other extractive. The body
of a normal-sized man contains about 90 grms., chiefly in the
muscles.

Creatine can be prepared by treating Liebig's extract of meat with baryta water
to precipitate phosphates, removing the excess of baryta with COo, and then
concentrating the filtrate on a water-bath to a thick syrup. In a few days a
crystalline deposit of creatine is formed. The crystals are transparent colourless
prisms, soluble in water, almost insoluble in absolute alcohol. On heating with

442 PHYSIOLOGY

dilute mineral acids creatine loses a molecule of water and is converted into
creatinine. Thus

NH^ /CH3 NH5. /CH3

NH,/ ^CH., NH/ \CH.

I - I "

COOH CO

On boiling creatine with baryta water it is split up into
urea and sarcosine — an amino-acid, according to the following
equation :

NH^

.CH3 NH,. .CH3

;C— N< +H.0= >CO + H— N<

NH/ \CH,.COOH " NH/ \CH,.COOH

Urea Sarcosine

and it is conceivable that a similar decomposition takes
place in the muscles, the sarcosine passing on to the liver,
and there being converted into ammonium carbonate and
then into urea. The following fact seems at first against
this view. Creatine taken with the food or injected into the
blood calls forth no increase of urea in the urine, the whole
quantity being excreted in the urine as creatine or creatinine.
We must conclude from this experiment that the creatine
does not leave the muscle as such, but that it is broken
down in the muscle into urea and an amino-acid, or still
further oxidised into ammonia and carbonic acid, which are
then turned out into the lymph and blood -stream.

Direct experiments by Schondorff seem to point to a formation of ammonia
in muscles during activity, and we know that C0._, is the most prominent
product of muscular metabolism. But in these experiments, which consisted
in the estimation of the ammonia in detibrinated blood before and after passage
through the vessels of a hind limb, the muscles of which were tetanised through
the nerve, there was also an increased formation of lactic acid. It is therefore
possible that the ammonia was the direct result of the production of acid and
therefore only indirectly due to the state of activity of the muscle. We
do not yet know whether lactic acid is produced in contraction of a muscle
under absolutely normal conditions, and therefore cannot regard Schondorff's
experiments as absolute proof of the formation of ammonia under such
normal conditions.

The various stages in the formation of urea from protein
may be roughly represented by the following schema :

FUNCTIONS OF THE KIDNEYS AND SKIN 443

Protein
hy hydrolysis breaks up into

Ammonia Amino-acids ' Hexone bases ' '

Urea

Alternative process ?

Protein

I .
Creatine {mode of conversion

unknown)

By oxidation)
\

1

Ammonia
By dehydration-.

1
and CO,

s8

■ CO
O

53:)

555

Sarcosine Urea
Oxidation |

NH, and CO.,

Dehydration \

Urea

' Nothing is known as to the fate of these substances in the body, though it
is highly probable that they, as well as the residue left after the hydrolysis of
arginine, undergo changes similar to those which have been proved to take place
in the case of the simple amino-acids.

444 PHYSIOLOGY

Uric Acid

Ukic acid (C.:iH^N403), which occurs constantly in the
urine in small quantities, is a weak dibasic acid. It is
almost insoluble in cold water — a little more soluble in hot
water. It is easily soluble in alkaline solutions and in solu-
tions of the alkaline phosphates. In solutions of the latter
salts a chemical change takes place, the uric acid with-
drawing a part of the alkali from the phosphate to form an
acid urate of the alkali, which is more soluble in water than
uric acid. Thus :

Na.HPO, + C^H.N.Oa = NaH^PO, + NaC.HgN.Oa.

The acid reaction of the urine is due to the presence of
the acid sodium phosphate. If the urine be allowed to cool, it

Fig. 211.

0^*^ □

Various forms of uric acid crystals. (Frey.)

is often found that crystals of uric acid separate out, and
the urine becomes less acid or even alkaline. This is due to
the fact that in cooling the mass-influence of the uric acid is
diminished. The phosphoric acid of the phosphate combines
with the soda of some of the acid sodium urate, forming
disodium phosphate and setting free uric acid, which is pre-
cipitated. If the urine be warmed again to the temperature
of the body, the converse reaction takes place, acid sodium
urate and acid sodium phosphate being formed, and the uric
acid is dissolved.

It may be prepared from urine by adding 5 c.c. of hydro-
chloric acid to 200 c.c. of urine, and allowing the mixture
to stand for twenty-four hours. Crystals of uric acid then

FUNCTIONS OF THE KIDNEYS AND SKIN 445

separate out (Fig. 211). These are generally coloured dark
red and form rhombic prisms. The red colour of the
crystals is due to the fact that they carry down with them
part of the pigment of the urme. If the urine is concen-
trated, there is very often a brick-coloured precipitate pro-
duced on cooling, which dissolves up again if the urine be
warmed. This is spoken of as the ' lateritious ' deposit, and
consists of the mixed urates of potassium, sodium, calcium,
and ammonium.

Three classes of urates are described. Taking H.,U to stand for uric acid,
the salts would be represented as M.,\J (normal urates), HMU (acid urates or
biurates), and HMLMI,_,U, or quadriurates. The biurates are the only stable com-
pounds. The normal urates, which are the most soluble, form strongly alkaline
solutions. The quadriurates are supposed to form the greater part of the
urates of urine, but split up spontaneously into biurates and uric acid. It is
doubtful whether the bodies described under this name are anything more than
mixtures of biurates and uric acid.

Tests for uric acid. — A few crystals of uric acid are
warmed with a little concentrated nitric acid in a porcelain
capsule until the nitric acid is evaporated. On adding a drop
of ammonia to the yellow residue, a brilliant purple colour
is produced (murexide). If potassium or sodium hydrate be
used the colour is blue.

Another method is to dissolve the substance in sodium
carbonate solution and to place a drop on filter paper pre-
viously moistened with silver nitrate. If uric acid is present
a yellow or black coloration is produced, due to the reduction
of the silver salt. This is known as Schiffs test.

Quantitative determination. — Hopkins' method for the
estimation of uric acid is founded on the fact that saturation
of a fluid containing uric acid or urates with ammonium
chloride causes complete separation of all the uric acid
present in the form of ammonium urate. In applying this
method the urine is saturated with crystals of ammonium
chloride, and a few drops of strong ammonia solution are
added. The precipitate of ammonium urate which forms is
collected on a filter, washed into a beaker, and boiled with
dilute hydrochloric acid. The urates are broken up, and the
uric acid thus set free is deposited in a crystalline form on
cooling. The precipitate of uric acid is collected on a weighed
filter, dried, and weighed.

446 PHYSIOLOGY

Chemical Relationships of Uric Acid A knowledge of the chemical rela-
tionships of uric acid is a necessary preliminary to any investigation of its mode
of origin in the body. We have already seen that it is a member of the group
of purine bodies.

N-CH

I 1

The formula of purine being CH C— NH\

II II ^CH

N C -N '^

HN CO

I I

that of uric acid is CO C— NHv

I II CO (i.e. trioxypurine).

HN— C— NH/

It is apparent from this formula that uric acid consists of a central three
carbon chain to which are attached two urea groups, and it is easy to under-
stand the synthesis of uric acid by fusing together trichlorlactic acid or
trichlorlactamide and urea.

Under the action of oxidising agents one or both of the urea groups is
split off.

Thus nitric acid splits off the right-hand group, forming urea and a body
known as alloxan.

NH— CO NH— CO

I I II

CO C— NH\ CO CO NH,.\

I II ;co + H„o + 0=1 I + ;co.

NH— C NH/ NH— CO NH,/

Further oxidation converts the alloxan into parabanic acid

NH— CO

CO

and C0.>,

NH— CO

and parabanic acid by hydrolysis is finally converted into oxalic acid

CO-OH

I and urea.

CO— OH

Potassium permanganate on the other hand attacks the central three carbon
chain at once, forming allantoin.

NH— CO NH.,

CO

CO and CO...

NH-CH-NH

From the allantoin by processes of oxidation and hydration both urea groups
may be split off as before.

FUNCTIONS OF THE KIDNEYS AND SKIN 447

Origin of Uric Acid

We have already seen that in bh'ds uric acid is formed
mainly in the liver from ammonia and probably lactic acid.
In this class the administration of amino-acids, ammonia, or
urea gives rise in every case to increased output of uric acid,
and we have reason to believe that the greater part of the
transformation is effected by the liver. These results how-
ever are no guide to the question of the origin of uric acid
in mammals, where this substance forms only a very small
proportion of the total nitrogen output.

The first question we have to decide is whether uric acid
is a by-product in the ordinary' processes of nitrogenous
metabolism or whether it is formed along special lines from
certain precursors contained in the food. If the former were
the case, we should expect to find a constant ratio between
the uric acid and the urea in the urine. Although on a con-
stant diet such a ratio does exist (average about 1 to 50), the
ratio is at once upset by certain alterations in the character
of the food. Thus the uric acid output is very small on a
farinaceous diet, and is very little affected by adding to such
a diet a large amount of protein in the form of white of egg.
A (relatively) large increase is at once observed if a full meal
of meat be taken, and a still greater rise is produced by
the ingestion of foodstuffs rich in cells, such as sweetbreads
(thymus or testis) or liver. The rise of uric acid output
following such a meal is very rapid, and precedes the normal
post-prandial increase of urea (Fig. 212, p. 448).

This connection of uric acid excretion with the ingestion
of cellular organs at once suggests a possible mode of origin
for the uric acid. We have already seen that the main con-
stituents of undifferentiated cells, as of their nuclei, belong to
the class of nucleo-proteins and nucleins, and that these, on
hydrolytic dissociation, give rise to a series of bases, xanthine,
h3^poxanthine, adenine, belonging to the purine group, i.e. to
the same class of bodies as uric acid itself. We have at present
no adequate evidence as to the effect of the administration
of these bases on the output of uric acid in man. It seems
probable however that part of the basic residue of nucleo-
proteins may undergo oxidation in the body and appear in
the urine as uric acid, while another part may avoid oxidation

448

PHYSIOLOGY

and appear as other less oxidised members of the group, the
so-called alloxuric bases of the urine. The nucleo-proteins
which give rise to the uric acid may be contained in the food,
or be produced in the disintegration of the nuclei, etc., of the
tissues of the body itself. Corresponding to these two origins
we may distinguish the exogenous uric acid, dependent on the
food, and an endogenous moiety arising from the metabolism
of the tissues. As to the organ in which the formation of
uric acid is carried on, we have very little evidence. It has
been found however that, whereas extract of fresh spleen
contains a fair proportion of xanthine, the passage of oxygen
through the splenic pulp for some hours causes a conversion
of this xanthine into uric acid.

Fig. 212.

'

■

n

■

-

J

\

y

V

,'

\

s

.

/

1

'

/

/

\

;

f

\,

s,

',

(

^

',

1

/

•'

N

\,

'.

\

/

>,

•

/

s

'

/

/'

^

V

•

-■

•

•,

-

\

<^

s

/

•

V

p>

,'

s

\

^

_

«

•^

1 1

\

u

I

2

1

2

.3

<j

f>

J

7

t

9

1

9

11

12

Curves showing the hourly excretion of uric acid and urea after a
single meal (Hopkins). The continuous line = uric acid output;
the dotted line = urea output.

The only disease in which there is a large increase in the output of uric acid
is leucliEemia, which is generally associated with enlarged spleen and augmen-
tation of the number of leucocytes in the blood. Since the post-prandial rise of
uric acid is also often associated with a certain amount of leucocytosis, it has been
suo^ested by Horbaczewsky that the uric acid is a special product of the
metabolism of the leucocytes. Other observers have however failed to detect a
parallelism between the number of leucocytes and the uric acid secretion under
all conditions.

The deposition of sodium urate in the joints, which occurs in gout, seems to
be due to a deficient excretion rather than to an increased formation of this
substance. The whole question is however extremely involved and in need of
further evidence with regard to the origin and significance of uric acid in the
normal organism.

FUNCTIONS OF THE KIDNEYS AND SKIN 449

In dogs the administration of uric acid or of hypoxantliine causes an
increased excretion in the urine, not of uric acid but of allantoine. Admi-
nistration of adenine, another purine base, apparently causes no alteration at
first in the nitrogenous constituents of the urine. The dog however finally
dies with suppression of urine, and it is found that the epithelial cells of the
renal tubules are desquamating and in many places full of uric acid infarcts.
It seems evident from these various facts that there is a chapter of purine
metabolism in the body, of which at present we possess only a few disconnected
pages.

The following table will serve to represent the relation of uric acid to the
other xanthine or purine bodies.

Uric acide CjH^NPj.

Xanthine CsH^N^O.,.

Hypoxantliine . . • . C^H^NjO.

Adenine .... . C5H5N5.

Guanine. ... . C.H.N.O.

Other Nitrogenous Constituents

Creatinine. — The creatinine in the urine is nearly all
derived from the creatine contained in the meat that is taken
as food.' It does not however disappear in hmiger, so that
a certain amount must arise in the metabolic processes of the
body itself. It may be that this quantity merely represents
a small percentage of creatine which has escaped further
decomposition in the muscles.

HiPPURic Acid. — This is only present in small quantities
in human urine. The large amount found in the urine of
herbivora is due to the fact that in their food are bodies
belonging to the aromatic group — the benzoic acid series.
If benzoic acid be administered to a man, it is excreted in
the urine as hippuric acid, which is a combination of glycine
with benzoic acid, with the elimination of a molecule of
water :

CH.,.NH.. CH,NH-CO.C,H,
C,H — COOH + I " ■= I ■ + H..0.

Benzoic acid COOH CO.OH

Glycine Hiiipuric acid

This synthesis is effected by the living cells of the kidney.
If defibrinated blood containing benzoic acid and glycine be

' According to Folin, however, all the creatinine of the urine is derived from
the metabolic processes of the body, any creatine contained in the diet being
oxidised, or if in excess, appearing in the urine unaltered as creatine.

29

450 PHYSIOLOGY

passed through the vessels of the kidney for some time, it
will be found that their place has been taken by hippuric
acid. In the same way, a small amount of hippuric acid is
formed if the kidney be chopped up and mixed with blood
containing benzoic acid and glycine. If the kidney cells be
first killed by exposure to a temperature of 65°, or to the
action of alcohol, no hippuric acid is formed, showing that
this synthesis is not effected by a mere ferment action, but
is intimately dependent on the life of the cell.

Ammonia. — Although this constituent occurs in normal
human urine only to the extent of about 0-7 gram 2^er
diem, it is of considerable importance, since it is a measure
of the formation or ingestion of acids by the body. If
ammonium chloride be given to a fed rabbit, it reacts with
the alkaline carbonates derived from the vegetable food to
form ammonium carbonate, and this is converted into urea,
and appears as such in the urine. If, on the other hand,
ammonium chloride be given to a carnivorous animal, there
is no such store of alkali to take up the hydrochloric acid.
The salt therefore appears in the urine unchanged.

In the same way if dilute mineral acid be injected into
the veins of a dog, the reaction of the blood remains normal,
but the excretion of ammonia in the urine is increased in
proportion to the acid injected. The tissues defend them-
selves agamst the acid intoxication by turning out ammonia,
and the ammonia in the urine is therefore increased at the
expense of the urea.

This self-protective ammonia formation is less marked in
herbivorous animals. In these, when the store of vegetable
alkaline salts is used, the acid causes a lowering of the
alkalinity of the blood. The carrying power of the blood
for carbon dioxide is therefore diminished (fixed acid having
taken the place of CO., and P.^0.,), and the animal sufi"ers
from a retention of CO2 in all his tissues, giving rise to
hyperpnoea and dyspnoea and finally to a condition of coma
which may end fatally.

An analogous condition occurs in cases of diabetes in
man. This ' diabetic coma ' has been shown to be associated
with the abnormal production of large quantities of oxy-
butyric and diacetic acids. The alkalinity of the blood as
well as its CO., contents is decreased, while the ammonia

FUNCTIONS OF THE KIDNEYS AND SKIN 451

of the urine is largel}' increased in the vain attempt of the
organism to saturate the offending acids.

The Salts of Urine

The greater part of the salts of the urine is derived
directly from the salts taken in with the food. The com-
binations of the vegetable acids with alkalies, e.g. citrates
and tartrates, are oxidised to carbonates, and are in this
form eliminated with the urine.

The pliofii-)liatef> originate partly from the breaking down
of complex phosphorised molecules, such as lecithin, nuclein,
and the nucleo-proteins, partly from the phosphates taken
in with the food. When the urine becomes alkaline, the
calcium and magnesium phosphates are deposited as an
amorphous precipitate. If the urine is ammoniacal, ammonio-
magnesium phosphate m^y be formed and precipitated in
a crystalline form.

The sulphur in the urine arises partly from the sulphates
of the food, and partly from protein metabolism. It is found
in the urine in three forms :

1. Small traces of an unoxidised sulphur compound, allied
to cystine.

2. As simple sulphates of the alkalies.

3. As conjugated ethereal or aromatic sulphates.

These latter bodies are important from the fact that they
are dependent on putrefactive changes occurring in the
intestine, so that their quantity in the urine is an index to
the extent of these processes. In the bacterial putrefaction
of proteins, bodies of the aromatic series, such as skatol,
indol, and phenol, are formed. These, after absorption,
unite in the blood-stream with an alkaline sulphate to form
conjugated or ethereal sulphates, and as such are excreted
by the kidnej^s. The poisonous aromatic body is thus
rendered innocuous.

OH .O.C.H,

C,H,OH + S0.< = SO., < + H.,0.

\0K " \0K

Phenol Acid potassium Potassium

sulphate phenyl sulphate

452 pnvsioLOGY

Indol and skatol undergo a preliminary oxidation to
indoxyl and skatoxyl before the conjugation with sulphuric
acid takes place. Thus :

NH. .NH.

C,H,< >CH + 0 - C,H,< >COH.

Indol Indoxyl

the indoxyl sulphate of potash having the formula

Indoxyl sulphate of potash is often spoken of as indican,
since on oxidation it yields indigo blue. If urine containing
this body be treated with hydrochloric acid and a drop of
chlorine water, a liright-blue colour is produced from the
formation of indigo.

Urinary Pigments

An exact knowledge of the pigments of the urine is
still wanting. The chief colouring matter is a body known
as urochrome. The chemical relationships of this body
have yet to be discovered. It has no distinctive absorption
spectrum. On treating however an alcoholic solution of
urochrome with aldehyde, a pigment is produced having an
absorption spectrum identical with that of urohilin, thus
pointing to a common origin of the two bodies. Urobilin
itself does not exist in normal urine, which presents no
absorption bands. On precipitating normal urine with lead
acetate, and extracting the precipitate with acid alcohol, a
small trace of urobilin is obtained. Normal urine therefore
contains a small amount of a chromogen, which on appropriate
treatment may give rise to urobilin. In certain diseases,
especially cirrhosis of the liver, the urine may contain large
amounts of pre-formed urobilin.

Urobilin free from other pigments may be extracted from
urine in the following way :- The urine is saturated with
ammonium chloride to throw down urates with the adherent
pigment iiroerytlirin, then filtered, acidified, and saturated
with ammonium sulphate. This throws down the urobilin,

FUNCTIONS OF THE KIDNEYS AND SKIN 453

but instead of waiting for the precipitate to form, the urobilin
may be dissolved out by shaking the ammonium sulphate
solution with a mixture of chloroform (one part) and ether
(two parts). The solution thus obtained is yellowish-red,
with a well-marked absorption band in the blue end of the
spectrum near the Fraunhofer line F.

Urobilin is certainly derived from bile pigment, and there-
fore indirectly from htiemoglobin. The stercobilin which is
formed from bilirubin in the intestines, under the reducing
action of putrefaction, is identical with urobilin. Urochrome
is probably a product of oxidation of urobilin.

Hydrohiliruhin, which is formed by the action of sodium
amalgam on bilirubin, presents many similarities to uro-
bilin, with which it was formerly thought to be identical. It
contains however about twice the proportion of nitrogen that
is contained in urobilin.

454

PHYSIOLOGY

Section 2
THE SECEETION OP UEINE

The kidney may be considered as a compound tubular
gland. On cutting into a kidney it is seen to consist of two
parts, a granular cortex, and a medullary portion presenting
radial striation. The medulla in the human kidney is
divided into a number of pyramidal segments, the Malpighian

Fig. 213.

Section of human kidney (Cacliat). a, cortex ; h, medulla
or Malpighian pyramids ; c, papilla ; d, ureter ; c e, boundary zone.

pyramids, each consisting of a number of tubules which open
at the apex of the pyramid, the papilla, into the dilated
extremity of the duct of the kidney — the ureter. Between
the cortex and medulla, in the region known as the boundary
zone, are seen a number of large blood-vessels cut across.
Small striated prolongations of the medulla stretch up from

FUNCTIONS OF THE KIDNEYS AND SKIN 455

the base of the pyramids into the cortex, forming the medul-
lary rays, or pyramids of Ferrein.

The urmary tubule starts in the cortex in a small dilata-
tion— the Malpighian capsule, which is Imed by a single
layer of flattened cells. Into this capsule projects the
glomerulus, a little bunch of capillary blood-vessels, also
covered by flattened cells. The capsule leads into the first
convoluted tubule, Imed with peculiar ' rodded ' epithelium.
The tubule now becomes much narrower, and dips down into
the medullary pyramids as the descending loop of Henle,
lined with flattened hyaline epithelium. It then widens as it
turns up again, and on reaching the cortex forms the irregular
tubule and the second convoluted tubule. These three last-
named parts are lined with rodded epithelium. From the

Fig. 214.

(.i;.

A iiortion of a convoluted tubule with ' rodded ' epithelium.
(Heidenhain.)

second convoluted tubule a junctional tubule leads into the
collecting tubule, which is lined with hyaline cylindrical cells.
There are thus four different varieties of epithelial cells
in the various parts of the tubule, i.e. scaly cells in the Mal-
pighian capsule, peculiar rodded epithelium in the convoluted
and irregular tubules, flattened cells in the descending loop
of Henle, and ordinary cylindrical cells in the straight col-
lecting tubes.

There are also certain peculiarities connected with the
blood-supply to the kidney. The renal artery breaks up into
numerous vessels at the boundary zone between the pyramids
and the cortex. From these the straight interlobular arteries
pass towards the surface, giving off lateral branches which
form the afferent arteries of the neighbouring Malpighian
capsules and break up in the glomerulus into a cluster of
fine capillaries. These unite again to form the efferent vessel,

456

PHYSIOLOGY

which is only two-thirds the diameter of the afferent vessel.
The efferent vessel leaves the glomerulus and breaks up
again into capillaries which supply the walls of the convoluted
tubules. Thus the arrangement of the portal system of
vessels is repeated in the kidney on a microscopic scale — the
vessel taking the blood from the glomerulus breaks up again
into a system of capillaries, just as the portal vein does in
the liver. The pyramids are supplied by branches of the vasa
recta which pass inwards from the arteries in the boundary
zone.

Fig. 215.

Cortex.

B mndary zone.

Medulla.

Diagram showing course of urinary tubules, and the distribution
of the blood-vessels (from Yeo).

This arrangement of blood-vessels must determine a high
pressure in the capillaries of the glomerulus, and a low
pressure in the vessels supplying the remaining parts of the
tubule. Since these capillaries are covered only by a thin
layer of scaly epithelium, it has been thought that filtration
plays a great part in the secretion of urine, and that perhaps
the fluid parts of the blood are merely filtered off in the
capsule, and the useful constituents of the filtrate, together
with the excess of water, reabsorbed in the tubules where

FUNCTIONS OF THE KIDNEYS AND SKIN 457

the pressure in the surroundmg capillaries is low. At any
rate the histological differences between the glomeruli and
tubules indicate that in the secretion of urine we have pro-
bably two distinct mechanisms at work, the glomerular and
tubular. It will be convenient to deal with these two func-
tions of the kidney separately.

According to the theory just enunciated, the glomerular
epithelium acts simply as a filter allowing the water and salts
of the blood-plasma to pass into Bowman's capsule. Such
a filtration presents no difficulties from a mechanical stand-
point. If blood-plasma be filtered through a clay-cell, the
composition of the filtrate obtained differs very little from
that of the original plasma. If however we make the filter-
ing medium denser by soaking it with gelatin, we find that
only the water and salts of the plasma will pass through, the
whole of the protein remaining behind. Under these circum-
stances, a certain limiting pressure is found at which no
filtration at all takes place. This pressure, which in the case
of blood serum amounts to about 30 mm. Hg, represents
the force necessary to effect a separation between the colloid
and fluid constituents of the blood-plasma. If the filtration
theory be correct, we should expect to find that a certain
minimal blood -pressure is necessary for any flow of urine
to take place at all, and that when the pressure exceeds this
minimum, the rate of secretion will be proportional to the
blood-pressure in the glomerular capillaries, or at any rate
to the difference of pressure obtainmg between the glomerular
capillaries and the urinary tubule.

The experimental investigation of this question shows
that in many cases at least the urinary secretion follows the
mechanical conditions just laid down. If the spinal cord be
divided in the neck, the blood-pressure falls to about 40 mm.
Hg and the urinary secretion ceases. On the other hand,
any procedure which increases the pressure and velocity of
the blood in the glomerular capillaries is attended with
augmented flow of urine.

The condition of the renal circulation in such experiments
is tested by placing the kidney in an oncometer. With free
venous outflow, every increase in volume of the kidney
denotes increased blood-pressure and blood -flow through that
organ.

458

PHYSIOLOGY

The parallelism
will be evident from

of vascular conditions and urinary flow
the following table of results.

Procedure

Geueral
blood-
pressure

Reual vessels

Kidney
volume

Urinary flow

Division of spinal cord
in neck

Falls to
40 mm.

Eelaxed

Shrinks

Ceases

Stimulation of cord

Rises

Constricted

Shrinks

Diminished

Stimulation of cord after
section of renal nerves

Eises

Passively
dilated

Swells

Increased

Stimulation of renal

Unaffected

Constricted

Shrinks

Diminished

nerves

Stimulation of splanch-

Eises

Constricted

Shrinks

Diminished

nic nerve

Division of one splanch-

nic nerve :

a. In dog

b. In rabbit .

Unaffected
Falls

Dilated
Eelaxed

Swells (?)
Shrinks (?)

Increased
Diminished

Plethora

Eises

Dilated

Swells

Increased

Haemorrhage

Falls

Constricted

Shrinks

Diminished

Under all these circumstances, in which the kidney
increases in volume, the amount of urine excreted by it is
increased. But we have here two factors, either of which
may determine an increased flow of urine— 1st, increased
blood-pressure in the glomerulus ; and 2ndly, increased flow
of blood through the kidney. It will be remembered that the
flow of lymph from a limb is markedly increased by ligature
of the veins ; and this increase is due chiefly to the enormous
rise of pressure that takes place in the capillaries, larger
than can be brought about by the constriction of the arterioles
in other parts of the body. If the secretion of urine were
similarly dependent on the intra-capillary blood -pressure, it
might be expected that ligature of the renal vein would also
cause an increase in the urine excreted. This is not the case.
Ligature of the renal vein entirely stops the secretion of
urine, and Heidenhain concludes therefore that the glome-
rular secretion involves the activity of the endothelial cells
of the capsule, and is conditioned not by the pressure but by
the velocity of the blood through the glomerular capillaries.
This operation of ligature of the renal vein is not however

FUNCTIONS OF THE KIDNEYS AND SKIN

459

a clean experiment. In the first place the small veins of the
kidney run alongside of the tubules and when dilated under
the influence of venous congestion may press upon the latter,
occluding their lumen and so stopping the flow mechanically.
Moreover ligature of the renal vein cannot be regarded as
equivalent to obstruction of the eft'erent vessels of the glome-
ruli. It will be remembered that there is a very great
difference as regards the effects on the intestmes between
ligature of the portal vein and obstruction of the inferior
vena cava above the liver. It is impossible to inject the
glomerular capillaries either through the renal portal capil-

FiG. 216.

Bowman's
C .>. p s u I e

Diagram (after Morat) to illustrate the effect of active changes in
the vasa afferentia and etferentia on the pressure in the
glomerular capillaries. If the vas afferens constricts, the
pressure will be represented by the lower dotted line. On
the other hand, constriction of the vas efferens would raise the
pressure in the glomerulus till it almost equalled that in
the renal artery, as is shown by the upper dotted line.

A, arteries ; G, glomerular capillaries ; C, tubular capillaries ;
V. vein.

laries in the frog or through the renal vein in the mammal,
and in view of the presence of well-developed muscular fibres
in the vasa afferentia, we have no proof that any given rise
of pressure produced in the venous side of the tubular capil-
laries is transmitted effectively to the glomerular capillaries.
It is a common experience to find, in injecting a kidney
shortly after the death of the animal, that it is impossible
to get any of the injection into the glomerular capillaries,
although the injection may flow freely through all the vessels
of the medulla.

The diagram (Fig. 216) will serve to demonstrate the

460 PHYSIOLOGY

great importance of contraction or dilatation of the mus-
cular fibres of vas afferens or vas efferens for the blood-
pressure in the glomerular capillaries, and this factor is
one which unfortunately it is impossible to estimate in any
experiment.

It stands to reason however that the velocity of the blood
must be at least as important as the blood-pressure in the
glomeruli. At any given time there is only a small volume
of blood in the glomeruli, and if this were not renewed the
transudation through the epithelium would concentrate it to
such an extent that transudation would be no longer pos-
sible under any pressure which the capillaries would stand.
In any rapid formation of urine therefore, it is absolutely
essential that there should be a rapid renewal of blood in the
glomerular capillaries as well as an adequate blood-pressure.

It is interesting to note that, if the renal veins be ob-
structed for a short time, the urine that is excreted after
the removal of the obstruction contains albumen, showing that
the short deprivation of oxygen undergone by the cells has
injured them, and that they are in consequence no longer able
to prevent the passage of the protein constituents of the plasma.

Functions of the, tuhules. — If we accept the view as to the
simple character of the glomerular function (a view that must
still be regarded merely as a working hypothesis), we must
assume that the glomerular secretion is an almost colourless
fluid having the same proportion of salts as the blood-plasma,
and like this containing only about 0*05 per cent, of urea. On
its way down the tubules this fluid is converted into urine,
containing 2 per cent, of urea, as well as salts in proportions
differing widely from that found in the blood-plasma. What
is the nature of the process occurring in the tubules ? Is it
one of absorption as Ludwig assumed, or is it one of secre-
tion, the specific constituents of the urine being added in
large quantity to the watery glomerular fluid '? A definite
decision between these two theories is not at present pos-
sible, although there is no doubt that in its original form
Ludwig's theory is untenable. Ludwig ascribed the concen-
tration to processes of diffusion occurring between the fluid
in the tubules and the lymph outside the tubules. As a
matter of fact if urine and lymph were in contact, separated
only by a permeable membrane, the urine would cause a
concentration of the lymph, since its osmotic pressure is

FUNCTIONS OF THE KIDNEYS AND SKIN 461

very much higher than that of the latter fluid. It is difficult
to believe however that tlie whole of the urea of the urine is
turned out by a process of filtration in the glomeruli, since, in
order to form the 1,500 c.c. of urine containing 30 grammes
of urea per day, the glomeruli would have to turn out 60,000
c.c. of urine, of which 58,500 would be reabsorbed by the
tubules.

We must see therefore what evidence there is of a secre-
tory function of the tubular epithelium. Older observers
described crystals of uric acid in the tubular epithelium of
the bird's kidney. In the case of the mammalian kidney it
is evidently impossible to trace such a soluble, inert body as
urea, and we must have recourse to colouring matters on
which the kidney has a special selective activity and which
can be detected on their way through the cells. Such a sub-
stance is sodium sulphindigotate. If this be injected into
the blood-stream, the urine within a minute or two acquires
an intense blue colour, although the blood may be only
slightly tinged with tlie dye. If during this period of secre-
tion the animal be killed and its kidney washed through with
absolute alcohol in order to fix the dye-stufif, the whole of
the kidney is found to be blue, and on microscopic section
the only parts free from the dye are the glomeruli. In order
to study the seat of excretion of the indigo we must stop the
glomerular secretion which carries the blue colour to all
parts of the tubule. For this purpose, before the injection,
the spinal cord is divided in the neck. The injection then
evokes no secretion, but on fixing the kidney in alcohol the
cortex alone is found to be blue, and on microscopic section
the indigo is found deposited in granules in the lumen and
within the striated epithelial cells of the first and second
convoluted tubules.

Having thus proved a specific secretory activity of the
striated cells of the convoluted tubules with regard to indigo
carmine, it is a reasonable assumption to make that these
cells exercise a similar function in respect to urea and pro-
bably for the other specific constituents of the urine.

Even if we grant this assumption, it seems necessarj^ to
allow also an absorbing function to the tubules. Thus it is
found that during the diuresis produced by injection of
mixtures of sodium chloride and sulphate, the sulphate is
excreted far more completely than the chloride, and this

462

PHYSIOLOGY

difference is exaggerated if we favour absorption by partial
obstruction of the ureter, owing to the greater ease of absorp-
tion of the chloride. It is possible that certain parts of the

Fig. 217.
Far body

Testis

Kidney

\tk, -AoKia

— Vena cava

Renal aKheries

Renal port-al
Ant. abdom.v.

-Femoral v.
The vascular supply to the kidney in the frop;.

tubules are secretory while other partis are absorptive in
function, but we are far as yet from any exact knowledge of
the part played by each segment of the tubule in the elabora-
tion of the fully formed secretion.

Fig. 218.
Renal art. ^

Renal portal

vein

Diagrammatic representation of the course of the blood-flow in the
frog's kidney, showing the double blood-snpply to the capillaries
round the tubules.

The ideal method of deciding the relative functions of the glomeruli and
tubules would be to collect the secretions of these two parts separately. In
the frog and newt, the kidneys have a double blood-supply, the glomerular
arteries being branches of the renal artery, whereas the urinary tubules derive
their blood partly from the vasa efferentia of the glomeruli, but partly also from
a branch of the femoral vein which forms what is called the renal portal system
(Figs. 217, 218).

FUNCTIONS OF THE KIDNEYS AND SKIN 463

It was shown by Nnssbaum that ligature of the renal arteries entirely cut
off the circulation through the glomeruli without interfering with the renal-
portal circulation ; and he stated that, although ligature of the renal arteries
stops the urinary secretion, the secretion can be at once induced by injecting a
solution of urea into the blood. He concluded therefore that the function
of the tubules is to secrete urea together with water. On the other hand, he
states that certain substances, such as sugar and peptone, which are readily
excreted by a normal kidney, are not excreted if the renal arteries have been
tied, even if a flow of urine be called forth by the simultaneous injection of urea
into the blood. It is concluded therefore that sugar and peptone pass into the
urine through the glomerular epithelium.

A recent investigation of this subject by Beddard has shown however that,
while Nussbaum's anatomical statements are correct, his conclusions are
probably fallacious, owing to the absence of control injections of the frogs
at the end of the experiment. It is very easy to miss some small vessel
going to the glomeruli and then to obtain Nussbaum's results with the
injection of urea, but if all the vessels to the glomeruli be ligatured, as proved
by a subsequent injection, the secretion of urine ceases absolutely and cannot
be evoked by any injection of urea. It seems that a certain supply of arterial
blood is necessary to the normal life of the tubular epithelium, since this
undergoes fatty degeneration and desquamates in consequence of the occlusion
of the glomeruli. These experiments have been repeated, an adequate supply
of oxygen to the tubular epithelium being provided by keeping the frog in an
atmosphere of pure oxygen. Under these conditions the desquamation of the
epithelium does not take place, and by injection of urea, a small flow of urine
can be induced. This must have been secreted by the tubules.

Begulation of urinary secretion.^ln most other glands
of the body we have seen that then- activity ^Yas subject to
nervous influences. The submaxillary gland is supplied by
secretory nerves, stimulation of which calls forth a flow of
saliva independently of any change in the blood-stream. The
conditions in the kidney however are diflerent. The func-
tion of this organ is to purify the blood of its waste products,
and hence it is only necessary that the cells should react
to changes in the composition of the blood. If the blood
becomes more watery, the excess of water must be turned
out into the urine ; if it contains too much urea or sugar,
these bodies must be excreted, in order that the blood may
act as a normal living medium, and not as a poison to the
tissues which it traverses. There is indeed no evidence of
secretory nerves to the kidney. The urinary secretion is
conditioned only by the composition and amount of blood
supplied to it. Injection of water or of diuretics, such as
sodium acetate or urea, into the blood, causes an expansion of
the kidney from dilatation of its vessels, and increased flow of
urine, until the blood is restored to its normal composition.

464 PHYSIOLOGY

The nervous system can influence this secretion of urine,
but only by its action on the vessels. In this way may
be explained the copious flow of dilute urine which may
occur under the influence of emotions or in hysteria.
Increased secretion of urine brought about by the applica-
tion of cold to the skin may be due to reflex dilatation of the
renal blood-vessels.

In the dog the vaso-motor nerves to the kidney pass
from the spinal cord chiefly through the anterior roots of the
11th, l'2th, and 13th dorsal nerves, and stimulation of the
peripheral ends of these roots causes shrinking of the kidney.
If slowly repeated rhythmical stimulation instead of the ordi-
nary faradic current be applied to these nerves, swelling of
the kidney may be produced, showing that these roots also
contain vaso-dilator fibres.

On tlie Work done by the Kidney

I have already mentioned certain arguments against the
hypothesis that the urine is separated from the blood circu-
lating in the kidney by a simple process of filtration. A still
stronger argument however is furnished by the fact that we
can measure the work done by the kidney in the secretion
of urine, and find that it is very much greater than could
be accomplished by the pressure of the blood in the renal
capillaries.

The measurement of the work done by the kidney depends
on a determination of the osmotic pressures of the blood-plasma
and urine respectively. Before describing these results, it
will be necessary to say a few words as to what is meant by
the term ' osmotic pressure.'

It is well known that, if a bladder containing strong salt
solution be placed in a vessel of distilled water, water passes
into the bladder by diffusion or osmosis, so that the bladder
swells and becomes tense. A manometer connected with the
bladder will show a considerable rise of pressure (osmotic
pressure). It is evident however that we cannot expect under
these conditions to get the total possible rise of pressure
in the bladder ; since the salt diffuses out of the bladder
while the water is diffusing in, and moreover the animal
membrane permits of a distinct filtration, i.e. leaks, as soon
as the pressure within it has attained a certain height. It is

FUNCTIOxNS OF THE KIDNEYS AND SKIN

465

necessary then, in order to measure the osmotic pressure of a
solution, to enclose it in some vessel whose walls will only
allow of the passage of water, and will not permit salt to pass
out either by diU'usion or by filtration. Such a vessel may
be made by washing out a porous cell, first with copper sul-
phate and then with potassium ferrocyanide. An insoluble
precipitate of copper ferrocyanide is deposited in the pores of
the earthenware, and it is found that these now allow only
water to pass through, and are perfectly impermeable to dis-
solved salts. If we arrange such a cell as in the diagram
(Fig. 219), fill it with 1 per cent. NaCl solution, and then

Fig. 219.

— MerciaicdMcmomefer

OiderTessel

coniainiricr
Distilled Watet:

Inner I^sscl (Scmipenneahle)
cordaintng l%,Jm..Ci. Solution.

suspend it in distilled water, we find that water diffuses in
until the pressure, as shown by the attached manometer,
has attained a great height. The osmotic pressure of a 1 per
cent. NaCl solution is equal to about 5,000 mm. Hg. If by
artificial means we increase the pressure in the cell above
this height, water will be pressed through the semi-permeable
walls of the cell, and the solution will become more concen-
trated. In order then to make a 1 per cent. NaCl solution
more concentrated, we must employ a pressure greater than
5,000 mm. Hg.

30

46G PHYSIOLOGY

Now it is found that the osmotic pressures of various sohi-
tioiis depend, not on the nature of the dissolved substance,
but merely on the number of molecules present in solution.
The osmotic pressure of any solution is in fact equal to the
pressure which the dissolved substance would exert if it
occupied the same space in the form of a gas.

Hence, if we can determine the osmotic pressures of the
blood-plasma and of the urine, we can estimate what w^ork
must be done by the kidney cells in order to separate from the
blood-plasma a fluid having the osmotic pressure of the urine.

We may take as example an instance quoted by Dreser in
which 200 c.c. urine had been secreted. The blood-plasma
in this case had an osmotic pressure equal to a 0'92 per cent.
NaCl solution. The urine had an osmotic pressure equal to
a 4*0 per cent. NaCl solution. It may be shown mathemati-
cally that in this case the kidney had performed 37 kilogram -
metres of work in the secretion of the 200 c.c. urine. Very
interesting is the determination in this way of the maximum
force of the kidney. In one case in which a cat had been
deprived of water for three days, the urine was so concen-
trated that it was equivalent to an 8 per cent, salt solution.
The blood-plasma in the same animal had an osmotic pressure
equal to I'l per cent. NaCl. The difference of osmotic pres-
sures in this case was equal to 498 metres of water, so that
the kidney had separated the urine from the blood against a
pressure of 49,800 grams per square centimetre. The abso-
lute force of human muscle {i.e. the weight it can just raise)
is 8,000 grams per square centimetre ; hence we see that the
mammalian kidney can exert a force six times greater than
the maximum performance of voluntary muscle.

Some observations of Bradford show that we have not exhausted the
subject of the functions of the kidney when we have described its action as an
excreting organ. If in dogs one kidney be first excised, and at a later period
half or two-thirds of the other kidney, it is found that the urine after the
second operation is largely increased in quantity, and contains much more urea
than it did under normal circumstances. This urea comes from the disintegra-
tion of the nitrogenous tissues, since the animal wastes rapidly and dies in a
few weeks. An explanation is yet wanting for the paradoxical fact that an
animal with one-fourth its normal amount of kidney substance should form and
excrete double the normal amount of urea. It is evident that the kidneys
play an important and hitherto unlooked-for part in nitrogenous metabolism,
but we are not yet in possession of sufticient facts to decide the exact extent
and nature of this function.

FUNCTIONS Oi< THE KIDNEYS AND SKIN 4CV,

Section B
MICTURITION

The urine is secreted continuously, although the amount
secreted may vary from time to time according to the con-
dition of the animal. Partly through gravity, partly through
the pressure under which it is secreted, the urine is driven
on through the ureters. If these be occluded, the secretion
of urine continues until its pressure reaches 60 to 80 mm. Hg,
when it ceases. This pressure is sufficient to distend widely
the up])er part of the ureters and the pelvis of the kidney.
In the ureters, which are muscular tubes lined with transitional
epithelium, the urine is driven on by peristaltic contractions,
which travel from the upper to the lower part of the ureter.
These contractions occur from three to ten times a minute,
and seem to originate in the muscular substance of the ureter
itself, since they are to be seen in an excised ureter. The
urine in this way gradually accumulates in the bladder ; its
reflux into the ureters is prevented by the oblique manner in
which these enter the bladder, a sort of valvular opening being
thus formed. At intervals the urine that is collected in the
bladder is expelled by contraction of its muscular wall. This
act of micturition is in the .young child purely reflex, and
dependent on the tension in the bladder. With advancing
age however the individual acquires more or less voluntary
control over the reflex act. It will be convenient to consider
first the purely reflex act of micturition.

The muscular wall of the bladder is generally described as
consisting of three coats, an external longitudinal, sometimes
known as the detrusor, and chiefly marked on the anterior
and posterior surfaces, a middle coat of circular fibres, which
are better developed towards the base of the bladder, and a
very incomplete internal coat of longitudinal fibres. In the
bladder no distinct demarcation can be made between the
various coats, and a bundle of fibres, which is at first longi-
tudinal, may dip inwards and run in a circular direction. No
distinct thickening of the circular coat to form a sphincter
can be made out at the vesico-urethral orifice, and on this

468 PHYSIOLOGY

account the circular muscle-fibres surrounding the prostate
have been described as an external spliiucter vrsiccc, and
have been regarded as the chief sphincter of the bladder.
This however would leave the female sex entirely without a
sphincter. Moreover in many animals the prostate is con-
fined to the dorsal side of the urethra, and does not run com-
pletely round it. It has therefore been suggested that the
urine is retained by the mechanical arrangements at the neck
of the bladder. Thus if fluid be injected into the bladder
through one of the ureters, a point is finally reached at an
internal pressure of about 120 cm, of water, at which the
fluid begins to escape from the urethra. The same result is

Fig. 220.

Ureter---

Prosrate-

Memb.'

observed if the experiment be tried onia dead animal, but in
the latter case the urethra does not contract after the passage
of the fluid, and so remains patent and filled with fluid. If
therefore the experiment be tried a second time, a very small
pressure suffices to bring about an escape of urine from the
urethra. On this account also the direction of the tension of
the bladder-walls is of considerable importance in determining
the amount of pressure necessary to overcome the resistance
of the urethral orifice. If the abdomen be opened, consider-
able pressure may be applied to the bladder in a downward
direction without any escape of urine, whereas if the bladder
be taken in the hand and drawn up, comparatively slight
pressure serves to expel its contents. When, as usually occurs,
the expelling force is rej)resented by the contracting walls of

FUXCTIONS OF THE KIDNEYS AM) SKIN 460

the bladder itself, the circulai- and longitudinal fibres both
co-operate in straightening the vesico-urethral canal and
forcing a tluid wedge into the beginning of the urethra.

A recent investigation by Kalischer of the structures at the neck of the
bladder has brought to light the existence of two distinct structures, both
of which must play some part in the normal retention of urine. The first
of these is a dense ring of unstriated muscular fibres, the sphincter frigonalis,
which encircle the beginning of the urethra in an oblique direction, as indicated
by the dotted line s s in Fig. 220, and are continuous with the muscle-fibres of
the trigonum (the space between the openings of the ureters). These fibres are
quite distinct from the circular fibres of the bladder.

Besides this involuntary sphincter, Kalischer describes another, consisting
of striated fibres which form a complete circle round the membranous portion
of the urethra, and an incomplete ring round the anterior part of the prostate.
This is the sphincter urogeniiaUa. Both structures, it will be observed, belong
not to the bladder but to the urethra, of which the trigonum is genetically
a part.

We must now inquire into the mechanism of the act of
expulsion. As the urine slowly trickles into the bladder, this
viscus first relaxes to accommodate the fluid, so that its con-
tents increase without a corresponding rise of intra-vesical

Fig. 221.

U, B.

20" ^

-VWl WAMWVAA,WA VW^UAAM\M/V\MMM/\\AMAAVv^\naAVv'vAAA/
Tracings of rhythmic contractions of urinary bladder. (Sherrington.)

pressure. With increasing distension however the pressure
in the bladder begins to rise, and this increased tension on
the muscular walls has the ordinary excitatory effect on the
muscle-fibre. Slow rhythmic contractions of the bladder
make their appearance and increase in force with increasing
tension on the muscular walls (Fig. 221).

The exact point at which, with increasing pressure, this excitatory effect
begins, depends largely on the rate at which the pressure is raised. A bladder
which normally would hold 250 c.c. of fluid, will not hold more than 100 c.c. if
injected rapidly by means of a syringe. In each case micturition would begin

470 PHYSIOLOGY

or, in the conscious animal, feelings of distress would occur, at the same intra-
vesical pressure, althouj^h the anrounts of fluid in the two cases are so very
different.

These rliytlimic contractions, causing a waxing and waning
of intra-vesical pressure, start impulses which travel up the
afferent nerves of the bladder to the lumbo-sacral cord, and
here a continual summation of these impulses goes on, until
finally, as the bladder is contracting, the stored-up impulses
break through all resistance and give rise to a reflex discharge
down the efferent motor nerves of the bladder. A strong
contraction of all the muscular fibres of the bladder is pro-
duced, causing a rise of pressure to 180 or even 150 cm. of
water, which overcomes the resistance of the tissues at the
neck of the bladder and continues until this viscus is emptied.
This evacuation may be aided by an associated contraction
of the abdominal muscles. Whether or not these events are
accompanied by an active relaxation of the ' sphincter ' or
* sphincters ' is still undecided. At the end of the act the last
drops are expelled from the urethra by rhythmical contractions
of the perinaeal muscles, especially the accelerator urina?
and levator ani, thus emptying this canal and restoring the
sphincter action of the tissues at the neck of the bladder.

The nerve-supply of the bladder is shown in the accom-
panying diagram (Fig. 222). It will be seen that it receives
nerves from two sources : firstly, from the upper lumbar
nerves ; and secondly, from the second and third sacral
nerves. The fibres from the latter source run direct to the
bladder in the nervi erigentes. Those from the upper lumbar
cord have a more circuitous course, by the rami coimminicantes
to the sympathetic chain, thence to the collection of ganglion
cells surrounding the inferior mesenteric artery, and from
this by the two hypogastric nerves to the bladder.

Stimulation of the upper set of nerves causes a feeble
contraction of the bladder-wall which, if one hypogastric
nerve be stimulated, is confined to the stimulated side,
and is always most marked at the base of the bladder.
Excitation of the pelvic nerves, on the other hand, causes a
strong contraction of the bladder, which is generally sufficient
to overcome the resistance of the sphincter, and so bring about
micturition. In many animals the upper nerve-supply also
carries some inhibitory fibres to the bladder-wall.

FUNCTIONS OF THE KIDNEYS AND SKIN

471

The sensory nerves of the bladder probably run in the
upper (sympathetic) supply.

According to some authors these two sets of fibres are antagonistic in
function. Stimulation of tlie liypogastric nerves is said to cause contraction of
the circular fibres of the bladder-wall, and therefore increased contraction of the
sphincter vesicJB, whereas stimulation of the nervi erigentes causes relaxation of

Fig. 222.

Sujf mes. ganglion. — •

Jnf: mesenteric
ganglion,

Jfypogdjtric
Hemes.

Hecftfm. —

gadder.

''.LumhaT jverfe^

':-/>ympal}idio chain.

•Lumhar mrve3.

--.J.EmSacral

" _; A'eri'i eriffenies.

tectum.
Diagram of nerve-supply to bladder. (Nawrocki and Skabitchewsky.)

the sphincter and a strong contraction of the detrusor urin®. The sacral fibres
are therefore those which are most important for the act of micturition. The
whole question of the behaviour of the sphincter however is in need of renewed
investigation, in view of the anatomical results mentioned above.

In the adult the processes of retention and evacuation of
urine are modified and controlled by voluntary effort. The
normal action of the sphincter mechanism may be aided by
the contraction of the perineal muscles which keep the
urethra closed. The reflex process of evacuation may be

47'2 PHYSIOLOGY

set in motion by voluntary contraction of the abdominal
muscles, by which the pressure in the bladder is increased
and the normal sphincter action overcome. It is probable
too that the individual has a certain degree of voluntary
power over the unstriated muscles of the bladder, and that
the contraction of the muscular wall may be directly aug-
mented by impulses proceeding from the cortex to the upper
part of the lumbar cord.

This view is favoured by the fact that stimulation of
the crus cerebri has been observed to cause contraction of
the detrusor urinae. In this experiment the abdomen was
opened, so there could be no question of the contraction of
abdominal muscles.

FUNCTIONS OF THE KIDNEYS AND SKIN 473

Section 4
THE SKIN

The skin, which covers the whole external surface of the
body, consists of a layer of stratified squamous epithelium,
the epidermis, resting on a layer of fibrous tissue, the dermis.
The epidermis is composed of several layers.

(1) The stratum Malpighii, resting on the papillae of the
dermis, and composed of several layers of cells which,
columnar below, become polygonal and flattened towards the
surface.

(2) The stratuvi granulosum, one or two layers of
flattened cells with many eleidin granules.

(3) The stratum lucidum, a layer of flattened nucleated
hyaline cells.

(4) The stratum corneum, produced by the conversion of
the cells of the subjacent layers, and consisting of horny
scales.

Keratin, which forms the main part of the horny layer of the skin as well
as of the skin appendages, such as nails, hairs, wool, feathers, horns, is an
insoluble resistent body closely allied to the proteins. On heating with acids it
gives the same decomposition products as the proteins, viz. leucine, tyrosine, and
other amino-acids as well as the hexone bases. It gives the xantho-proteic
and Millon's reactions, but is distinguished from other proteins by the high
percentage of sulphur contained in its molecule (2-5 to 5 per cent.). The
greater part of the sulphur is present in the form of cystine.

The dermis consists of a close meshwork of interlacing
white fibres, together with connective tissue cells, blood-
vessels, lymphatics, and nerves. At its under surface it
passes insensibly into the subcutaneous tissue, which also
consists of interlacing fibrous bundles, but with coarse
meshes, giving a loose texture to the tissue. These meshes
often contain a large amount of adipose tissue.

Two forms of glands are found in the skin, the sebaceous
and the sweat glands. These may be considered separately.

Sebaceous glands.— These always occur in connection with
the hair follicles. The hairs are formed by a transformation
of certain cells of the stratum Malpighii, which have grown
down into the dermis or subcutaneous tissue to form a hair
follicle. The hairs are always set obliquely. At the neck of

474 rHYsioLOtJY

the follicle, where the stratum conieum of the surface skin
comes to an end, we find the openings of the sebaceous glands.
These' are saccular, with a definite basement membrane which
is lined by a layer of columnar cells not differing greatly from
the lowermost cells of the Malpighian layer. The lumen of
the gland is however also filled with cells, which are large
and swollen, staining feebly with hfematoxylin, and presenting
quantities of fat granules. These degenerated cells are
the secretion. Instead of the protoplasm of the cell manu-
facturing and storing up the secretion, as is the case with
salivary glands, it is itself converted into sebum, the cells so
used up and destroyed being replaced by proliferation of the
cells nearest the basement membrane.

The secretion is composed of various neutral fats mixed
with fatty acids, and has an acid reaction. It is interesting
to note that a considerable amount of the fatty acids are in
combination, not with the tribasic alcohol glycerin, but with
the monatomic alcohol cholesterin. These cholesterin fats,
which are present also to a large extent in lanolin or wool
fat, have the advantage of not decomposing readily, so
serving as an efficient protection to the skin,

Eunning from the superficial part of the dermis to the
under surface of the hair follicle is a bundle of smooth
muscle-fibres, the arrector pili. Contraction of these muscles
can be excited by direct application of cold (as in produc-
tion of ' goose skin ') or by the nervous system through the
pilomotor nerves, and results in erection of the hairs. As
these muscles contract, they press at the same time on the
sebaceous glands and squeeze out some secretion on to the
root of the hair.

The course of the pilomotor nerves has been very thoroughly worked out by
Langley. It may be stated as a general rule that they follow the same course
as the vaso- constrictor nerves, leaving the spinal cord by the anterior roots
from second dorsal to third lumbar, and passing as fine medullated fibres into
the sympathetic chain by the white rami communicantes. In the ganglia they
end, and new relays of non-medullated fibres, starting from the ganglion cells of
the sympathetic chain, go by the grey rami to the nerve-roots, in which they
pass to their destination in the skin.

The sweat-glanch are composed of coiled tubes situated
in the subcutaneous tissue. Their secreting portion forms
about half the coil and is bounded by a basement membrane
and lined by a single layer of cubical cells. Between the

FUNCTIONS OF THE KIDNEYS AND SKIN 475

cells and the basement membrane is a layer of spirally
arranged smooth muscle-fibres, which are especially well
marked in the glands of the axilla. The duct is lined by
two or three layers of cells until it arrives at the epidermis,
where it is continued to the surface as a simple corkscrew
channel between the epithelial cells.

Sweat, the secretion of the sweat-glands, is a clear colour-
less fluid, with peculiar odour and a salt taste. It is gene-
rally acid in reaction, from the admixture of the secretion of
the sebaceous glands. If the skin from which it is obtained
be first thoroughly cleansed, the sweat that is subsequently
collected has a neutral or slightly alkaline reaction. It con-
tains a few epithelial scales derived from the skin, and about
2 per cent, solids, of which sodium chloride makes up the
greater part. Traces of fatty acids — formic, butyric, and
propionic -are also present. Under pathological conditions
urea, sugar, and other substances are found. Many drugs
after administration reappear in the sweat.

The secretion of sweat is constantly going on. If only a
small amount is formed, it is at once evaporated, and goes oil"
into the atmosphere as insensible perspiration. If, on the
other hand, the amount secreted be large, or the surrounding
atmosphere moist so that evaporation cannot easily take
place, the sweat collects on the surface of the body as sensible
perspiration.

The quantity of perspiration given off is considerable, but
varies so much that it is impossible to give an average figure
for the amount. It is increased by imbibition of large quan-
tities of fluid, especially if warm, by a warm atmosphere, or
by anything which tends to increase the amount of heat
formed in the body, such as muscular exercise.

The fact that sweating is so constantly associated with a
warm skin seemed at first to show that the secretion of this
fluid was called forth by the increased supply of blood to the
surface of the body and to the sweat-glands. This view
however is negatived by the fact that sweating may coincide
with a pale ansemic skin, as in the cold sweats of phthisis or
of the death agony, or associated with mental emotion,
especially extreme fear. The activity of these glands, as of
the salivary glands, is under the control of the central ner-
vous system. Stimulation of the peripheral end of the cut

470 PHYSIOLOGY

sciatic nerve of the cat causes abundant secretion of sweat
on the toes supplied by that nerve. If, on the other hand,
the sciatic nerve on one side be cut, and the cat asphyxiated,
sweating occurs in the toes of the other three limbs, but not
in the limb the nerve of which has been cut. Stimulation
of the sciatic nerve causes contraction of the blood-vessels,
so that the secretion of sweat cannot in this case be deter-
mined by an increased blood-supply. We can indeed excite
secretion of sweat by stimulating the sciatic nerve of an
amputated leg.

Secretion of sweat may also be excited reflexly. Pungent
substances taken into the mouth may cause abundant per-
spiration on the face.

The course of the sweat-neives in the cut has been investigated by several
observers, especially by Langley. In this animal the hairless pads of the feet
are the only parts of the body where sweat is secreted. The sweat-nerves to the
hind foot leave the cord chiefly by the anterior roots of the first two lumbar
nerves, and passing along the white rami to the sympathetic chain make con-
nections with cells in the sixth and seventh lumbar and first two sacral ganglia.
From these ganglia grey rami carry the impulses along to the corresponding
spinal nerve-roots and to the sciatic nerve.

The sweat-nerves to the fore-limbs leave the cord by the sixth, seventh, and
eighth dorsal nerve-roots, and all have their cell-stations in the stellate ganglion,
whence non-medullated fibres carry the impulses to the nerves of the brachia,
plexus and so to the paw. The nerve-cell connections of these fibres have been
determined by the nicotine method already described (p. 2(35).

The sweat-glands may likewise be affected peripherally.
Injection of pilocarpine calls forth secretion of sweat between
the toes, even after the sciatica have been cut. It is found
that the secretion produced by stimulation of the sciatic is
much increased by warming the air surrounding the toes.
The importance of this secretion for the regulation of the
body-temperature will be spoken of in the next chapter.

Cutaneous respiration. — In the frog, a large amount of
gaseous interchange takes place through the skin, so that the
animal may live a considerable time after the extirpation of
the lungs. In man, the skin and dead cuticle are much too
thick to allow any great interchange to take place between
the gases of the blood and the surrounding atmosphere. It
is reckoned that on the average from 5 to 8 grms. of CO^ are
given off by a man from the skin in twenty-four hours, and
a considerably smaller amount of oxygen is absorbed through
the same agency.

FUNCTIONS OF THE KIDNEYS AND SKIN 477

It was formerly tliought thai various poisonous products
were excreted with the sweat, and that retention of these in
the body might give rise to sjanptoms of poisoning. It seems
however that if a man's skm be clean, the sweat is perfectly
innocuous, and it is found that a man may be varnished all
over without suffering much harm. In rabbits, which do not
sweat, varnishing the body all over causes rapid death of the
animal, but this death is due simply to excessive loss of heat,
and may be prevented b}^ wrapping the animal m cotton wool.
Varnishing this animal seems to cause dilatation of all the
superficial capillaries, and hence a great discharge of heat
from the surface of the body. The only function of any
importance therefore, that can be ascribed to the secretion
of sweat, is the regulation of the heat discharge from the
bodv.

478 PHYSIOLOGY

CHAPTER XI

FATE OF FOODSTUFFS IN THE ORGANISM-
METABOLISM

Section 1
PEOTEIN METABOLISM

Having studied the paths by which the foodstuffs are
absorbed and waste products removed from the body, it re-
mains to inquire into the changes that take place in the food
after its absorption. We assume from our experience with
the various tissues, especially muscle, that the combustible
parts of the food are built up, together with oxygen, into the
living protoplasm of the cell to form a highly unstable
molecule with large potential energy. In the breakmg down
of this molecule there is a rearrangement of atoms to form
more stable compounds, the carbon and oxygen combining
into carbon dioxide with the evolution of energy, which may
be displayed either as heat or work.

We are still far from being able to follow the changes that
the foodstuffs undergo on entering into the living protoplasmic
molecule. Up to this point however we can, though with
many gaps in our chain of facts, follow the fate of foodstuffs
in the body ; and a short account of these facts, which are
grouped together under the term 'metabolism,' is the object of
the present chapter.

In all experiments on metabolism we must be able to
make an exact comparison of the Income and Output of the
body. To this end the food must be weighed and analysed,
and the oxygen taken in measured by means of some respira-
tory apparatus. The output of the body includes the carbon
dioxide and water expired by the lungs ; the urine, contain-
ing chiefly the nitrogenous excreta ; the faeces ; the carbon
dioxide and water given out by the skin as perspiration, and a

FATE OF FOOD.sTUFFS IX THE ORGANIS^NI 479

slight loss dependent on the wearing away of the cuticle. In
a balance-sheet of the organism the faeces should be subtracted
from the income, since they represent the undigested parts
of the food.

It has been thought that in a normal animal the excreta
may possibly have a twofold origin, and may come partly
from the breakmg down of the living protoplasm of the body,
partly from the direct oxidation of the food that is continu-
ally being taken in. It must be remembered however that
we have no evidence of any oxidative destructive changes in
the tissue juices or blood, and that the whole weight of ex-
periment points to the cells being the sole seat of all meta-
bolic changes. It will be convenient to consider first the
simplest condition, in which the animal takes no food, in
order that we may have only the metabolism of the living
tissues themselves to deal with.

In starving animals the income of the body is limited to
the inspired oxygen and, in most experiments, to a certain
amount of water. During an experiment of this sort, the
animal is weighed every day, and the amount of nitrogen
excreted and carbon dioxide given off by the lungs carefully
estimated. Preliminary experiments have shown us the
amount of nitrogen contained in muscle, so that from the
amount of nitrogen excreted we can estimate the degree of
disintegration of the muscular tissues that has gone on.
From the quantity of CO2 eliminated we can determine the
loss of the carbonaceous part of the body. This may be
regarded as composed entirely of fat, since the amount of
glycogen and carbohydrates in the body is small in com-
parison with the fat present. These two amounts (proteins + fat
lost) subtracted from the daily loss of weight leave a remainder
which represents the output of water. Adult animals, supplied
with water only, live for four or five weeks. During this
time they suffer gradual loss of weight, and at death have
lost about 50 per cent, of their weight. The excretion of
CO2 and water sinks continually until death takes place. The
urea excretion falls considerably within the first four or five
days, and then remains almost constant at a low level for
about four weeks. At the end of the fourth week there may
be a sudden rise in the amount of urea excreted. At this
])eriod every trace of fat has disappeared from the body.

480 PHYSIOLOaY

The animal has no further store of carbonaceous material to
draw upon, and so must consume the protein of its tissues in
order to su])ply the necessary proportion of heat and work.
In the emaciation consequent upon starvation it is observed
that the tissues whose energies are most necessary for the
carrying on of the vital functions suffer least. Thus the
heart and the central nervous system lose only 3 per cent,
of their weight. Of the fat, on the other hand, 97 per cent,
disappears, of the muscle 30 per cent. ; and a considerable
decrease of weight is also observed in the bones, liver, blood,
and alimentary canal.

The nitrogen that is eliminated during starvation must
necessarily arise from the disintegration of the proteins of
the body. As we have just seen, this amount during certain
periods of starvation is fairly constant from day to day. It
might be thought that, if an amount of protein were given to
the animal containing a proportion of nitrogen equivalent to
that which the starving animal was excreting, the loss of
nitrogen to the body would be checked, the loss of nitrogen
in the urine being replaced in the tissues by the nitrogen of
the food. This is however not the case. After the adminis-
tration of the protein to the starving animal, the quantity of
urea excreted is almost doubled, showing that nearly the
whole of the protein taken in is disintegrated within twenty-
four hours and excreted with the urine. In order to pro-
duce a condition in which the amount of nitrogen eliminated
is equal to the amount of nitrogen taken in with the proteins
of the food, it is necessary to give the animal at least two
and a half times the amount of protein corresponding to
the nitrogen that is excreted during starvation. In this case
the animal is said to be in a condition of 'nitrogenous
equilibrium.'

The condition of the protein metabolism in an animal
that is living on a purely protein diet and is in a state of
nitrogenous equilibrium deserves a little further consideration.
The fact that, to maintain the animal in this condition, two
and a half times as much protein is required as is necessary
to replace disintegrated nitrogenous tissues in the body, has
been regarded as showing that not all the protein in the food
can be devoted to this object. It has been supposed by Yoit
that the protein taken in with the food has a twofold destina-

FATE OF FOODSTUFFS IN THE ORGANISM 481

tion in the body, part of it going to supply the tissue waste,
and being built up into the living protoplasm of the tissues
(morphotic or tissue protein) ; while the other and probably
greater moiety passes into the juices that bathe the proto-
plasmic elements of the cells, and is rapidly broken up and
oxidised there without at any time forming an integral part
of the protoplasm. This is spoken of as circulating protein.

I have however already drawn attention to the numerous
experiments on the subject, carried out chiefly by Pfliiger
and his pupils, all of which tend to prove that the sole seat
of oxidative processes in the body is the living cell.

Some experiments, which were carried out by Schonclorff under Pfliiger's
guidance, are of especial interest in this question. According to Voit the
greater excretion of in-ea in a protein-fed animal is due to the fact that there
is an increased circulation of a fluid that is rich in proteins round the cells.
According to Pfliiger's views however, the presence of a greater or less amount
of protein in the nourishing medium would not be the determining factor for
the amount of urea formed, which would be regulated simply and solely by the
condition of the cells themselves. To decide this point, defibrinated dog's blood
was led alternately through the hind limbs and the liver of another dog, in
order to get the products of metabolism of the limb tissues and then convert
them into urea by passing the blood through the liver.

1. In one set of experiments the blood from a dog that had been starved for
flve days was led through the organs of a well-fed dog. In these experiments
Schondorff found that, without exception, the urea in the blood was largely
increased at the end of the experiment.

2. In a second series of experiments the blood of a fasting animal was led
through the hind limbs and liver of a fasting animal. In these the amount of
urea in the blood was unaltered.

3. In a third set blood of a well-fed animal was led through organs and liver
of a fasting animal. In these cases the amount of urea was always diminished.

It was concluded from these experiments that the extent of protein metabolism
depends on the nutritive condition of the cell and not on the condition of the
protein contained in the circulating tissue juices.

We must therefore conclude that the whole of the protein
metabolism takes place in the living cells, and not in the l^^mph
or blood-stream. How far it is necessary for all the protein
to be built up into tissue protein it is however difficult to
say. We may at any rate adopt Voit's view as to the twofold
destination of protein, provided that we introduce certain
modifications into his description of the events that take place.

Protein, as indeed all food, has a twofold object. In the first
place the whole of the activities of the body are associated
with the discharge of energy. The source of this energy is the
food, and, so far as we can tell, the value of a given foodstuff

Bl

482 PHYSIOLOGY

for this purpose is determined, apart from its digestibility,
solely by its heat value, i.e. the amount of energy it will set
free in combining with oxygen to form the end products of its
metabolism in the body.

The heat-values, i.e. the amount of heat evolved by the
combustion of one gram of the substance, for the three main
classes of foodstuffs are as follows —

Fats . . . .9-3 calories

Proteins . . . . 5'5 ,,
Carbohydrates . . . 4*0 ,,

In the body, while the combustion of fats and carbohydrates
is complete, part of the protein molecule is oxidised only
as far as urea, which has a heat-equivalent of 2-5 calories.
Since one gram of protein gives rise to 0-3 gram of urea, it
is necessary, in order to get the real heat-value of protein
in the body, to subtract 0-8 from the above figures, giving
a corrected value for proteins of 4- 7 calories. In man and
herbivora the total needs of the body cannot be satisfied on
a purely protein diet. In the normal diet given on page 508,
the protein represents only about one-sixth of the total
energy of the food.

The calorie here employed is the amount of heat which is
necessary to raise the temperature of one kilogram of water
one degree Centigrade.

As a source of energy it is apparently a matter of indiffer-
ence whether the organism is supplied with proteins, fats, or
carbohydrates.

Far otherwise is it with the other destination of protein.
The greater part of the living structure of the body is com-
posed of proteins, or of more complex nitrogenous bodies in
the building up of which the proteins play a preponderating
part. In the young and growing animal these tissues are
constantly being added, and the raw material for growth can
be supplied by protein, and by protein only. Moreover, in the
period of adult life, when the body is neither gaining nor losing
weight, every vital act is associated with a certain degree of
what we may term ' wear and tear ' of the living structure.
Few of the cells of the body have a life coterminous with that
of the whole organism. Most of the cells are continually
dying and being replaced by fresh ones. For this mitri-

FATE OF FOODSTUFFS IX THE ORGANISM 483

tional metabolism a supply of proteins in the food is an
absolute necessity. Every diet therefore must contain a
certain minimum amount of protein to supply the nutritional
needs of the organism, while the energy requirements can be
supplied at the expense of either proteins, fats, or carbo-
hydrates.

The physiological value, however, of these three classes is
not entirely expressed by their heat values. The organism
has the power of storing up any excess of fat or carbohydrate
above its energy requirements in the form of fat, which can
be utilised for the future activities of the organism. Its
power of storing up protein is however extremely limited.
In some animals overfeeding with protein may produce a
growth of muscles, which may be regarded as forming, in
some sense, a protein storehouse. In most animals, including
man, this power is practically absent. Load the animal as
we will with protein, two days of starvation will suffice to
exhaust any store of protein or nitrogenous materials, and
the excretion of urea sinks to the starvation minimum, its
amount being determined by the size and activities of the
animal and the amount of fat available for the supply of the
energy requirements of the body. On the other hand, feeding
the animal with excess of protein only leads to increased
excretion of urea. If for instance a man were taking 10
grams of nitrogen in the form of protein in the day with a
sufficiency of fats and carbohydrates to maintain his weight
constant, he would probably excrete also 10 grams (9 grams
in the urine, 1 gram in the faeces), and would therefore be in
a state of nitrogenous equilibrium. On doubling the protein
intake, the nitrogenous excretion would rise in proportion, i.e.
to 20 grams, and the man would remain in a state of nitro-
genous equilibrium however much his protein intake were
increased. The increased protein diet would, however, raise
his energy income above his daily requirements. A certain
amount of the fat and carbohydrate would therefore escape
oxidation and w^ould be stored up in the form of fat, and the
man would therefore increase in weight. It is impossible in
man to push this experiment very far, since a large excess
of protein diet gives rise to digestive disturbances, and the
experiment has to be discontinued.

It is evident that, given a sufficiency of fatty and carbo-

484 PHYSIOLOGY

hyclniie food, the minimum protein possible in any diet repre-
sents the nutritional needs of the body for nitrogen. Many
experiments have been made to determine this minimum. It
probably varies considerably in different individuals. Just as
some machines undergo greater wear and tear, and others
require a greater consumption of coal to perform a certain
amount of work, so it is with animals and men, and it would
be dangerous to lay down rigid laws for diet from observations
on a few individuals. The minimum amount of protein
required in any diet may probably be put at about GO grams,
though some individuals may keep in good health on a still
smaller amount. Any protein above this amount may be
regarded as concerned, together with fats and carbohydrates,
in supplying the energy requirements of the body.

The minimum need for protein cannot be determined from
experiments on fasting animals. In these there is often a
deficiency of fat, and, after a few days, of carbohydrate, and
the protein metabolism may therefore be concerned, not merely
in maintaining the nutrition of the working tissues, but also
in supplying a certain amount of the energy required for the
different activities of the body.

FATE OF FOODSTUFFS IN THE OKGANISM 485

Section 2
FOEMATION OF FAT

If, while the animal is in a state of nitrogenous equi-
librium, larger amounts of fat or carbohydrates be given than
are necessary for its daily consumption, the animal increases
in weight, and the excess of carbonaceous material is deposited
in its body in the form of fat. On a purely protein diet no
very large amount of fat, if any, is ever deposited in the body.
A formation of fat from protein, though not proved under
normal circumstances, has been thought to occur under patho-
logical conditions in the higher animals and in many lower
organisms. Thus if dogs, that have been starved till all fat
has disappeared from the body, be poisoned with phosphorus,
a large increase in the nitrogen excretion is observed, and
when the animal dies all its organs are found to be in a state
of fatty degeneration, and to contain two or three times the
normal amount of fat. In this case there is apparently a
splitting up of the protein molecules of the tissues into a
nitrogenous moiety, which is excreted, and a carbonaceous
moiety, which is retained in the cells in the form of fat. It
is more probable, however, that the fat deposited in the cells
is the product of conversion of carbohydrate or fat molecules
transported from other cells of the body. Evidence in favour
of the fat in fatty degeneration of the liver being deposited
rather than formed in situ is afforded by the fact that, if the
poisoned animals be fed with abnormal fats, these fats are
found forming part of the fat in the degenerated tissue. In
the ripening of cheese, which is accomplished by the agency
of low organisms, there is a conversion of protein into fat. If
the eggs of fly-maggots be allowed to develop on a blood-clot,
the maggots, when full-grown, will be found to contain ten
times as much fat as there was previously in the blood-clot
and eggs together ; so that in this case the maggots have
been able to convert the protein of the blood-clot into fat.
We must conclude therefore that proteins may be converted
into fat in the living organism, although it is very doubtful
whether any such conversion takes place in the higher animals
under normal conditions.

486 PHYSIOLOGY

It was long doubted wlietlier the fat in the food could be
directly deposited in tlie body as such. It was supposed
that the fat in the food exerted merely a sparing effect on
the fat in the body formed from the proteins— that the fats
absorbed from the alimentary canal served to supply the
organism with an oxidisable material, and so shielded from
oxidation the fat in the tissues that had been formed from
protein. We have however conclusive evidence that the
fats taken in with the food can be deposited in the body
as such. Thus two dogs were fed, one with linseed oil, the
other with mutton suet, for a considerable period. The fat
in the tissues of the former was liquid at 0° C, while the fat
of the latter had a melting-point at above 50°. In another
experiment, in which a dog had been fed with colza oil,
erucic acid, which is an ingredient of colza oil, but absent
from animal fat, was found in the fat of the dog after
death.

Not only are neutral fats thus absorbed from the intestine
and deposited in the body, but also fatty acids. If these be
administered to an animal the greater part is absorbed, and
it is found that in the chyle of the thoracic duct nearly the
whole of the fat is present as a neutral fat and not as a fatty
acid, showing that, in the passage of the fat from the intes-
tine through the wall of the villi into the lacteals, there
has been a synthesis of fatty acid with glycerin. This is an
interesting fact, since glycerin is at no time found free in the
animal body, although we see that the epithelial cells of
the intestine can supply sufficient of it to unite with nearly
the whole of the fatty acid absorbed.

Long experience has shown the farmer the value of carbo-
hydrates as fattening food. As in the case of fats, the
question has arisen whether the carbohydrates are converted
into fat, or whether they have only a sparing influence on
the hypothetical fat formed from the proteins of the food.
That the former is the case is shown by the following ex-
periment. Two young pigs, ten weeks old, of the same
litter, with approximately equal weights, were taken. One
was killed, and the fat and total nitrogen in the body
estimated. From the amount of nitrogen the maximum
possible quantity of proteins present was calculated. The
second was fed on barley for four months. The barley was

FATE OF FOODSTUFFS IN THE OROxANISM 487

measured and analysed, as well as the amount of undigested
fat and protein that passed through the animal. At the
end of the four months the second animal was killed and
analysed. It was found that the animal contained 1'5G
kilos more protein, and 86 kilos more fat. It had taken
up with the food 7'49 kilos more protein, and 0'66 kilo fat.
If we subtract the protein added to the body (1"56) from
that taken up with the food (7*49), there is a remainder of
5-93 kilos which might possibly have given rise to fat.
But 7*9 kilos of fat had been added in the body— a far
larger amount than could pos.sibly have arisen from the
maximum amount of protein left over for the purpose. At
least 5 kilos of fat in this experiment must have been
derived from the direct conversion of the carbohydrates of
the food. We must conclude that fat can be formed directly
from carbohydrates, although how and where this conversion
takes place is at present quite unknown. We have however
parallel instances in the formation of butyric and other acids
of the fatty acid series from sugar by means of certain
organised ferments.

As w^e sliould expect, peptones may be used entirely to
replace the proteins of the food, and the animal will maintaiii
or even increase its weight on such a diet.

Gelatin cannot take the place of proteins in the food.
As we have seen, it differs from ordinary proteins in certain
important chemical relationships. If given in the food, it
has, like carbohydrate and fat, a sparing effect on the protein,
so that nitrogenous equilibrium is attained with a smaller
amount of protein than would be the case if no gelatin were
given. If a dog be fed on gelatin and fat, the excess of the
nitrogen excreted over the nitrogen taken in is less than
when the same dog is fed on fat alone, showing that the
gelatin has sheltered from disintegration some protein con-
stituents of the body. It has been said that gelatin can take
the place of circulating, not of tissue protein. It would
probably be more correct to say that, containing as it does
only certain of the ordinary constituents of the protein
molecule (tryptophane and tyrosine, for example, being
absent), it can only partially replace protein in supplying the
nutritional needs of the tissues.

Since fat represents a store of food in the body, -it is

488 PHYSIOLOGY

evident that a reduction of the fat can be effected only in two
ways, either by increasing the energy demands of the body,
as by muscular work, or by diminishing the energy supply by
lessening the food supply, i.e. by starvation. A man of 70
kilos doing a moderate amount of work needs about 40
caolries per kilo body-weight each day, i.e. his diet must
have a heat-value of about 3,000 calories. If this supply be
reduced, he will begin to use up the supply of energy repre-
sented by the fat of his body ; and all the obesity cures take
advantage of this fact. In some all the foodstuffs are dimi-
nished at the same time ; in others, as in the Banting cure,
the man is allowed to eat as much lean meat as possible, only
fats and carbohydrates being restricted. In this case a very
rapid diminution of body-fat results. This diminution has
been ascribed to a specific stimulating effect of protein on
metabolism. Such an explanation is unnecessary. A man
who is eating even five pounds of lean meat a day is being
starved. "Whereas his daily requirements are 3,000 calories,
he is getting with his food only 2,300 calories, and as a
matter of fact no man can continue to eat such large quan-
tities of meat. Three pounds of meat a day, a more usual
quantity, would have a heat- value of about 1,400 calories,
and it is not surprising that the organism makes good the
large deficit by feeding on the stored-up fat of the body.

FATE OF FOODSTUFFS IN THE OKGANISM 489

Section 3
HISTORY OF CARBOHYDEATES IN THE BODY

Normally, the blood of man and dogs contains from 0*05
per cent, to 0"15per cent, of sugar (dextrose). If this amount
be artificially increased by the injection of sugar into the
blood, it is found that, as soon as the amount of sugar rises
above 0*2 per cent., the excess is eliminated by the kidneys
and appears in the urine. After a meal rich in carbohydrates,
such as the Irishman's mess of potatoes, a very large amount
of sugar passes into the blood of the portal vein. Several
hundred grams however of carbohydrates may be ingested
without any sugar appearing in the urine. Again, in the
interval between meals when no sugar is passing into the
blood, the amount of sugar remains constant, although we
have reason to believe that it is incessantly being used up by
the muscles and other tissues of the body. There must be
some means therefore by which the overloading of the blood
with sugar is guarded against, at the same time that the
sugar percentage of the blood is maintained constant during
periods of temporary starvation. This function is subserved
by the liver, the great chemical factory of the body. This
is shown by the fact that, if a solution of dextrose be slowly
injected into a mesenteric vein, no sugar appears in the
urine, whereas glycosuria is at once produced if the injection
be made into the jugular vein.

Just as plants have the power of transforming sugar into
starch, which is deposited as a reserve material in their
tubers and similar organs, so the liver has the power of
seizing upon the excess of sugar passing through its capil-
laries and transforming it into a colloidal substance, which is
deposited in the meshes of the cell-protoplasm. This colloidal
substance belongs to the group of starches, and is called
glycogen or animal starch.

Preparation of glycogen. — A rabbit is well fed with carrots
or arrowroot for a couple of days. It is then killed by
decapitation, the liver cut out and thrown into boiling water,

490 PHYSIOLOGY

and boiled for about ten minutes. The pieces are then
ground up with sand to a line paste, returned to the same
water, and boiled for half an hour. While the mixture is
still boiling, a few drops of acetic acid are added until the
reaction is very faintly acid. In this way practically all the
proteins are coagulated. The mixture is then thrown on a
filter, and an opalescent fluid runs through containing only
the merest traces of protein. From this fluid the glycogen is
precipitated as a white amorphous powder by addition of two
volumes of 90 per cent, alcohol. It may be purified by solu-
tion in water and reprecipitation by alcohol ; it is finally
washed with alcohol and ether and dried. It may be freed
from adherent traces of protein by boiling with alcoholic
solution of potash, in which the glycogen is insoluble.

The glycogen so obtained is a white powder, free from
taste or smell, dissolving in hot or cold water to form a
strongly opalescent solution. With iodine its solutions give a
port-wine coloration. It may be distinguished from erythro-
dextrin by the fact that it is precipitated on saturation with
ammonium sulphate, or by 60 per cent, alcohol, whereas
dextrin needs nearly 90 per cent, alcohol for its precipitation.
Its relationship to starch is shown by its composition
« (C,iII|„0-,) and by the fact that on hydrolysis it yields dextrins,
maltose, and finally dextrose.

In the liver treated in the manner described above we find
only the merest traces of sugar. If however the liver be left
for some hours after the death of the animal before extraction
with boiling water, the extract will be found to contain much
less glycogen, but very large quantities of sugar. We see
that after death a process takes place in the liver by which
the glycogen is converted into sugar. This sugar is dextrose.
The conversion may take place even after the cells have been
subjected to the action of absolute alcohol for a considerable
time. This fact shows that the conversion is due to the
presence in the liver of some substance which may act as an
amylolytic ferment, converting starch or glycogen into sugar.
This ferment is destroyed by heat, and it is on this account
that the liver is thrown into boiling water in order to obtain
the maximum yield of glycogen.

Circumstances influencing the formation of glycogen. —
The amount of glycogen present in the liver at any given

FATE OF FOODSTUFFS IN THE ORGANISM 491

time is intimately dependent on the food taken. If an animal
be starved, the glycogen in the liver diminishes quickly at
first, and more slowly afterwards. After prolonged starvation
the liver contains only the merest traces. If a rabbit, deprived
of glycogen b}^ starvation, be given a meal of carbohydrates
and killed a few hours later, the liver will be found to contain
large quantities of glycogen.

Although carbohj'drates furnish the chief material for
the manufacture of glycogen, yet we have evidence that the
organism is able to form glycogen out of proteins. If a dog,
deprived of glycogen by long starvation and work, be fed for
a few days on a diet of washed fibrin perfectly free from
carbohydrates, the liver will be found to contain a fair
quantity of glycogen, though the amount is many times less
than that formed on a diet of carbohydrates.

Fats have no influence on the formation of glycogen. The
glycogen disappears as rapidly in an animal fed on fat alone
as in starvation.

Much more efficacious than starvation in causing dis-
appearance of the hepatic glycogen is muscular work. If a
dog be starved for a day and be then made to drag a heavy
milk-cart about all the next day, there will be found only the
merest traces of glycogen in its liver.

Glycogen also occurs in the muscles, where it probably
serves as a local supply of reserve material for the furnishing
of muscular energy. The glycogen must be conveyed from
the liver to the muscles and other organs of the body in the
form of sugar, since we cannot detect any glycogen in the
Idood. The importance of glycogen as a reserve material is
shown by the fact that it is present in very large quantities
in embryonic muscle, at a period when the formation of new
muscular fibres is going on most intensely.

We may also look upon glycogen as a source of heat. If
the temperature of a rabbit be lowered by immersing it in a
cold bath, the glycogen is found to have disappeared from the
liver after a few hours.

492 PHYSIOLOGY

Glycosuria

Under certain circumstances the power of the liver to
store up the glycogen may be temporarily destroyed. If a
puncture {piqure, or diabetic puncture) be made in the floor
of the fourth ventricle between the nuclei of the auditory and
vagus nerves, the animal for the next twenty-four or thirty-
six hours will suffer from glycosuria ; that is to say, sugar
will pass into the urine. At the end of this time the liver
will be found to be quite free from glycogen. If, on the other
hand, the animal be first deprived of glycogen by starvation
and work, the diabetic puncture will be without eflect, showmg
that the glycosuria is due to the rapid conversion of the
hepatic store of glycogen into sugar. This is turned out into
the blood-stream, where it raises the percentage amount of
sugar so high that the excess is excreted by the kidney-cells
and appears in the urine. Temporary glycosuria may be
brought about by various other means, such as poisoning by
strychnine or curare. After administration of chloral and
some other drugs, a reducing body appears in the urine,
which was formerly thought to be dextrose. It has been
proved however that in this latter case the reducing body is
not dextrose, but an oxidation-product of dextrose, glycuronic
acid (C,;H„0„).

It is interesting to note that, in the formation of glycuronic acid, the
oxidation has attacked the end of the molecule furthest away from the aldehyde
COH group, perhaps pointing to the fact that the sugar molecule is attached to
the protoplasmic molecule by this, its most unstable group. The formula of

COOH
glycuronic acid is (CHOH)^. It is apparently being constantly formed in the

COH.
body in the oxidation of dextrose, although special means are necessary to fix
it in this stage before it has undergone further decomposition. Thus phenol
when administered to a dog is normally excreted in ethereal combination with
sulphuric acid. If however the dog be fed on a farinaceous diet poor in proteins
the administration of phenol is followed by its excretion in combination with
glycuronic acid, i.e. an acid derived from carbohydrate metabolism instead of
one derived from the metabolism of proteins.

The results of the administration of phloridzin throw some
light on the carbohydrate metabolism of the body. Phloridzhi
is a glucoside found in the root cortex of apple and cherry
trees. If a certain amount of this be administered to a

F^TE OF FOODSTUFFS IN THE OEGANISM 493

dog, sugar appears in the urine after a few hours, and the
glycosuria lasts for two or three days. If the dog be killed at
the end of this time, the liver and muscles are found totally
free from glycogen. We might thus come to the conclusion
that the sugar was derived from the glycogen stored up in the
body, and from that alone, as is the case after the diabetic
puncture. But if, when the glycosuria has ceased and the
body is quite free from stored-up glycogen, a second dose of
phloridzin be given, a still larger amount of sugar is excreted.
As the dogs were starved during the experiment, this sugar
must have been derived from protein. Thus we see that
sugar as well as glycogen may be manufactured in the body
directly from protein.

Although both after administration of phloridzin as well
as after diabetic puncture, there is disappearance of glycogen
from the liver, the causation of the glycosuria in the two
cases is quite different.

The blood normally contains about 0"05 to 0"15 per cent,
of dextrose. This does not escape into the urine, since normal
urine contains only minimal traces of dextrose. If however
the percentage of sugar in the blood rise above 0*2 per cent,,
the excess is at once excreted by the kidneys. Thus a flush-
ing of blood with sugar (either by excessive absorption from
the alimentary canal, by artificial injection of dextrose oi
abnormal conversion of the liver glycogen) will bring about
glycosuria.

After the injection of phloridzin however, the amount of
sugar in the blood is found to be rather diminished than
increased, and this diminution is most marked in the blood
of the renal vein. If phloridzin be injected into one renal
artery, the corresponding kidney at once begins to secrete
sugar, and the kidney of the opposite side follows suit only
after some minutes' interval. We must conclude therefore
that the primary action of this drug is on the kidney, exciting
it to secrete the sugar normally present in the blood, and
thus reducing the percentage of sugar below normal. The
matter however will not rest here. The function of the liver
is to keep the amount of sugar in the blood normal. As soon
therefore as it receives the blood which has been impoverished
in"sugar by the abnormal action of the kidneys, it will take
of its store of glycogen, turning out sugar into the blood until

.194 PHYSIOLOGY

the normal composition of this fluid is restored. And so these
contending processes will go on, the liver pouring sugar into
the blood, and the kidneys at once excreting it out of the body.
This struggle will continue until the hepatic store of glycogen
is exhausted, and then, if the kidneys are still under the
influence of phloridzin, the liver will attack the proteins in
order to keep up the sugar supply, and there will be a rise of
urea excretion in the urine which will run exactly parallel to
the amount of sugar in this fluid. It has been suggested
that the phloretin, the nitrogenous constituent of phloridzin,
may act as a carrier of sugar across the renal epithelium,
combining on one side with the blood-sugar to form the
glucoside phloridzin, which is then broken down again by the
cells into sugar, which is excreted on the other side, and
phloretin, which is free to repeat the carrying process.

In the disease known as diabetes, in which the patient
passes large quantities of sugar with the urine, the immediate
cause of the glycosuria is an increased amount of sugar in the
blood, amounting in some instances to as much as 0*4 to 0*6
per cent. Some of these cases may be due to defective power
of the liver to store up glycogen, so that the excess of sugar
taken in with the food passes at once into the general circula-
tion, and is excreted by the kidneys. Such cases maybe suc-
cessfully treated by limiting the amount of carbohydrates taken
in with the food. This however cannot be the explanation of
the ordinary cases of severe diabetes. In these the patient
passes sugar even during starvation or on a pure protein diet,
just as in the case of a dog poisoned with phloridzin. In
these cases glycogen may be found in the liver after death, so
that this function of the liver is certainly not wanting. The
passage of sugar into the urine probably depends on the
inability of the organism to utilise the sugar taken in with
the food or split off from the proteins of the body. It is found
therefore that the excretion of urea is also increased. In
fact, the man is in the condition of an animal fed on proteins
alone. Since the carbohydrates cannot be utilised, the
organism has recourse to the proteins to cover the whole
expenditure of energy, and hence the increased excretion of
urea.

Why tlie power of utilisation of the sugar is defective we
do not know. It may be that the sugar has to be further

FATE OF FOODSTUFFS IN THE OEGANISM 495

elaborated in certain organs before it can be nsed up by the
general tissues of the body. Such a function of elaboration
may possibly belong to the pancreas, since this organ has
been found diseased in about one-fifth of the fatal cases of
diabetes. Whether or not the pancreas is at fault in all cases
of diabetes is not _yet known. There is no doubt however
that this organ is in some way connected with the sugar
metabolism of the body. If the pancreas be extirpated in a
dog, the animal acquires severe diabetes, which proves fatal
in a few weeks. The glycosuria continues even on a pure
protein diet or during starvation, and under these circum-
stances a constant relation is found between the urea and the
dextrose, showing that the latter has been derived from the
disintegration of protein. The same conclusion may be drawn
from the severe wasting of the muscular tissues which occurs.
In a little time other abnormal products of metabolism
appear in the urine oxybutyric and aceto-acetic acids, as well
as aceton derived from a decomposition of the latter acid.
In this respect the pancreatic diabetes resembles the severe
diabetes of man. The abnormal formation of these acids leads
in time to an acid intoxication, the animal dying in a state of
coma, the so-called ' diabetic coma.'

The exact causation of this form of diabetes is unknown,
although many theories have been proposed, all equally un-
satisfactory. It is necessary to extirpate the whole organ,
since partial excision, ligature of the duct, or division of all
the nerves to the gland does not produce diabetes. On this
account it has been suggested that the epithelial cell-nests
(islets of Langerhans) of the pancreas are the important
structures, whose excision involves the production of diabetes.
Pathologists who have attempted to test this hypothesis by
an adequate examination of the pancreas in fatal cases of
diabetes have arrived at divergent results. We have already
seen however (p. 329) that these islets in all probability
represent phases in the activity of the secreting tissue of
the gland, and do not need therefore to be endowed with a
special function apart from that of the rest of the gland.
Moreover we do not get any nearer to a solution of the ques-
tion by saying that the pancreas has an internal secretion,
since we have no conception how such a secretion may work.
It has been stated that in pancreatic diabetes the sugar in

190 PHYSIOLOPtY

the urine disappears after excision of the liver, showing that
in this, as in the other forms of glycosuria, the liver is the
great sugar factory of the body.

The whole question of diabetes is however too difficult to
be dealt with at greater length here. Although the researches
into its causation have thrown some light on the normal
carbohydrate metabolism of the body, the light is at present
only sufficient to intensify the black shadows of ignorance that
obscure almost every part of our knowledge of the subject.

FATE OF FOODSTUFFS IN THE OEGANISM 497

Section 4
THE SOUECE OF MUSCULAE ENEEGY

It was always maintained by Liebig that the foodstuffs
might be divided into two main groups — the carbohydrates
and fats that gave rise to the heat produced in the body,
and the proteins which were the source of muscular energy.
This view was however refuted once and for all by the
classical experiment of Fick and Wislicenus (1865). These
observers ascended to the summit of the Faulhorn, which is
1,956 metres high. The urine they secreted during the six
hours' ascent and during the succeeding six hours was col-
lected, and from the amount of nitrogen contained in this
was calculated the amount of protein that was used up during
this time. It was found that in the case of Wislicenus 37
grms. protein had undergone oxidation. It was calculated
that the oxidation of this quantity would produce 250 heat
units (the unit of heat here employed is that amount of heat
necessary to raise the temperature of one kilogramme of
water one degree Centigrade). This heat is equivalent to
about 100,000 kilogrammetres of work. But Wislicenus
weighed 76 kilos, so that in raising his body to the height
of 1,956 metres he had performed 76x1,956 = 148,656 kilo-
grammetres of work. There was moreover a large expenditure
of energy in the movements of the heart and respiratory
muscles, which is not taken into account here ; so that the
amount of work done was far larger than could be accounted
for by the oxidation of proteins.

If the income and output of a man be compared for several
days, on some of which work is done, while on others no
work is done, it is found that the consumption of oxygen and
the production of CO^ are much larger on the working days
than on the resting days, and that in fact the increased
oxidation of carbon which takes place is sufficient to account
for the energy expended. The nitrogen excretion on the
other hand is only slightly increased. This slight increase
may be due to the increased wear and tear of the protoplasmic
mechanism of the muscle, and is not nearly sufficient to
account for the energy expended.

32

498 PHYSIOLOGY

If a clog be starved for six successive days, and on the
last three be made to do hard work, it is found that the
increase in the excretion of urea on the last two days is still
quite small. As we have already seen, one day's starvation
and hard work are sufficient to get rid of all glycogen from the
body. Hence it is evident that in the last two days the
greater part of the energy for the performance of muscular
work must have been derived from fats. We must conclude
that normally the fats and carbohydrates are the chief sources
of muscular energy.'

If however an animal be fed on a pure protein diet, work
increases the excretion of urea, since the energy in this case
has to be derived from the disintegration and oxidation of
proteins. Muscle draws its energy from all three classes of
foodstuffs. So long as carbonaceous food is supplied in suffi-
cient quantity, or is present in the body in the form of fat or
glycogen, the muscle chiefly makes use of this for the energy
required in the contraction. If this is not given, or if the
carbonaceous stores of fat and glycogen are used up, muscular
work must be maintained by the disintegration and oxidation
of protein.

In ' training ' for severe muscular exertions it has long
been customary to give an excess of protein diet. Since in most
cases the process of training involves the growth of muscular
tissue, and therefore an addition to the pro']ein structures of
the body, a certain excess is justifiable. Bat there seems to
be no object in increasing the protein beyond what is necessary
to supply the material for this hypertrophy. A well-trained
man certainly works more economically (i.e. with less wasteful
heat formation) than an untrained man, as is shown l)y the
respiratory exchanges of the two individuals. But for the
production of this trained condition of ' fitness ' it is the con-
stant exercise and the healthy life, together with the absence
of superfluous fat round the muscle fibres, that are the chief

' But not on a mixed diet, the sole source. The absence of influence of
moderate exercise on the respiratory quotient shows that in work an animal
utilises the same foodstuffs as at rest, i.e. that the muscle draws its energy from
all three classes of food. This increased katabolism would be followed by a
greater appetite and therefore increased intake of all three classes. Only when
the income of protein is restricted do we find a sparing of the precious protein,
so that the energy of the contracting muscles appears to come from the combus-
tion of carbonaceous material alonp.

FATE OF FOODSTUFFS IN THE ORGANISM 499

factors, and there is no sufficient proof that a muscle works
more economically at the expense of protein than at the
expense of carbohydrate or fat. In fact the ultimate and
chief source of energy in protein, as in carbohydrates and fats,
is the oxidation of the carbon of the molecules, and there
seems to be no advantage to the body in complicating this
process with the splitting off of nitrogen, or in loading the
tissues and circulating iluids with the numerous interme-
diate products which occur in the oxidation breakdown of the
protein molecule.

500 PHYSIOLOGY

Section 5
ANIMAL HEAT

All the energy that is set free by the decomposition and
oxidation of the foodstuffs appears as work or heat. It has
been reckoned that about nine-tenths of the energ}'' set free
in the body appears in the form of heat, and one-tenth is
represented by the work done. In the chapter on Muscle
we saw that its efficiency as a heat-engine varied within very
wide limits, the proportion of heat evolved to work done in
muscular contraction being from 5 : 1 to 25 : 1. Even if we
take the lowest of these estimates, we see that a very large
proportion of the heat produced in the body must be evolved
by the muscles. The increased production of heat attendant
on bodily exercise is familar to every one. If the spinal
cord of an animal be. excited by faradic currents, so as to
cause tetanic contraction of all the limbs, the production of
heat in the muscles is so large that the temperature of the
animal may rise to 110" or 112'' Fahr. — a rise which is fatal.

Next to the muscles in importance as a source of heat to
the body is the liver. In fact, under normal circumstances
the temperature of the blood in the hepatic vein is higher
than in any other part of the body. Wherever active pro-
cesses of katabolism are going on there is an evolution of
heat. Probably there is a similar evolution of heat accom-
panying the activity of every gland in the body.

We must also look upon the brain as a source of heat,
since thermometers inserted in it may register a higher
temperature than that of the blood which is supplied to
the brain. The amount of heat produced here is however
insignificant compared with that formed in the muscles and
liver.

On the processes of metabolism — the decomposition and
oxidation of foodstuffs — depend the maintenance of life.
Hence all living animals are continually producing heat and
imparting it to the surrounding bodies ; and unless this heat
production is more than counterbalanced by loss of heat in
surface evaporation, they must have a higher temperature

FATE OF FOODSTUFFS IN THE ORGANISM 501

than the surrounding medium, although the difference may
not amount to more than two or three degrees in cases where
metabolic processes are going on sluggishly.

With respect to their internal temperature, animals may
be ranged into two main classes : (1) those which have a
fixed temperature, which is within certain limits independent
of the surrounding medium — liomoeothermic animals ; (2) those
in which the temperature varies with that of the surrounding
medium — poikilothermic animals. To the first class belong
birds and mammals, including man ; they are often spoken
of as warm-blooded animals. The lower Vertebrata, including
reptiles, amphibians, and fishes, and the Invertebrata, belong
to the second class of poikilothermic animals.

We must now inquire into the means by which this
regulation of the internal temperature in warm-blooded
animals is effected. The temperature of an animal is the
algebraic sum of two factors — the amount of heat produced
and the amount of heat lost in a given time. If, while the
heat production remains constant, the amount of heat
imparted to the surrounding medium be increased, the tem-
perature will fall. If, on the other hand, heat loss remaining
constant, heat production be raised, the temperature will rise
in the same proportion. So the temperature may be regulated
by alterations in the heat production or in the heat loss ;
and if the temperature is to remain constant, there must be
an accurate correlation between the two processes.

Begulation of Heat Prochiction

The heat production in an animal may be measured in
two ways, either directly or indirectly.

The direct measurement of the heat production in an
animal is fraught with many difficulties, and it is doubtful
if any satisfactory form of calorimeter has yet been devised
for the purpose. In order to determine the heat of com-
bustion of any substance, the ordinary ice or water calori-
meter is perfectly satisfactory. In the case of a mammal
however we have to maintain a constant circulation of air
through the apparatus and otherwise to keep the animal
under as normal conditions as possible. One of the best
calorimeters for this purpose is that devised by Haldane and

502

PHYSIOLOGY

Hale White, in whicli the heat production of an animal is
balanced against the heat produced by burning hj^drogen.
The number of units of heat given off b}' the animal to the
apparatus can be directly calculated from tlie number of
grammes of water produced by the l)urning hydrogen in the
same time.

The calorimeter consists essentially of two precisely similar chambers,
A and B, each of which has double walls of sheet copper with an intervening air-
space. Both air-spaces communicate with the two limbs of the manometer m,
which therefore serves as a differential thermometer, the slightest difference
of temperature in one chamber causing an expansion of the air and consequent
displacement of the fluid in the tube. Air is led through the chambers by the
tubes T, leaving by the tubes t', care being taken that the ventilation in both
chambers is the same. The air is dried before entering by passing over pumice

Fig. 223.

Differential calorimeter of Ilaldane, Hale White, and Washbourn.

and sulphuric acid. The air which leaves also passes over sulphuric acid. The
animal is placed in the cage in r, and the hydrogen flame in a lighted, and the
height of the flame is adjusted by altering the current of hydrogen until the
fluid in the manometer m remains absolutely stationary. The heat production
in the two chambers must now be the same, and can be determined by weighing
the sulphuric acid bottle on the exit tube of a before and after the experiment,
the amount of water formed giving the quantity of hydrogen burnt and there-
fore the total heat produced.

The practical carrying out of these experiments involves
BO many difiticulties, that in most cases it is more convenient
to have recourse to the indirect method, i.e. to measure the
output of the animal in CO^ and the income of oxygen, and,
judging from the respiratory quotient the character of the

FATE OF FOODSTUFFS IX THE OEGANISM 50S

foodstuffs destroyed, determine from tlie known heat of
combustion of these foodstuff's the total heat production of
the animal during the experiment. The data will of course
be more accurate if the urea excretion be also measured and
taken as an index to the protein used up.

It has already been mentioned that, if a frog or other
cold-blooded animal be exposed to a higher temperature, its
internal temperature ^Yill also rise. If, at the same time,
we measure the respiratory interchanges of the frog, we find
that at the higher temperature more carbon dioxide is
evolved and more oxygen taken up, showmg that in this
case a rise of temperature in the surrounding medium causes
a rise in the temperature of the frog, and at the same time
increases the activity of its metabolic changes. Cooling has
the reverse effect. If a frog be cooled to 0° C, the chemical
changes in its tissues are so reduced that it may be kept
alive for some days in an atmosphere devoid of oxygen.
The case is quite otherwise with warm-blooded animals.
Exposure of one of them to a cold medium raises the amount
of carbon dioxide given off' and oxygen taken in, while the
temperature of the animal remains unaltered. This power
of the animal to react to changes in the temperature of the
surrounding medium is dependent on the integrity of the
nervous system and its connection with the muscles. If a
dog or rabbit be poisoned with curare (which paralyses the
muscle end-plates), or if its spinal cord be divided just
below the medulla, its temperature sinks continuousl3^ It
is then found that the animal reacts to changes in the
temperature of the surroundmg medium precisely like a
cold-blooded animal — rise of the external temperature
causing rise of the internal temperature and increased
elimination of CO^, while a fall of the external temperature
has the reverse effect.

It is still a subject of debate, what is the exact nature
of the action of the central nervous system on the heat
production of the body. It is evidently effected through
the muscles, and, partly at all events, by means of muscular
contractions. The increase of the tone in the muscles, and
the general stringing up of the body after a cold bath, are
an example of this. If the cold be more severe, the reflex
contractions are more pronounced, and take on a clonic

504 PHYSIOLOGY

character, as shivering and chattering. A man too has
recourse instinctively to muscular exercise to ward off the
effects of extreme external cold. It has been thought how-
ever that the nervous system has a distinct influence on the
thermogenic properties of muscles apart from its action in
producing muscular contraction ; and that nervous impulses
may call forth chemical changes in the muscle which give
rise to heat and heat only. This view is supported by
several phenomena, such as the increased production of heat
in fevers, accompanied by a rapid wasting of the muscles,
although the muscular tone in these cases is depressed
rather than heightened. If the anterior part of the corpus
striatum be pricked or stimulated, the animal suffers from
pyrexia or rise of internal temperature for a day or two ;
and this rise is accompanied by increased elimination of CO2
and production of heat. No special motor pheromena are
observed in these experiments, and it has therefore been
concluded that the increased heat production is due to a
direct thermogenic action of the injury.

Begulation of Heat Loss

Far more important however than the regulation of the
temperature by the production, is the regulation by the loss of
heat. The channels of loss of heat may be classified as follows :

1. By the urine and faeces. In the warming of the food
and drink taken into the body, there must be a certain
abstraction of heat from the tissue surrounding the alimen-
tary canal, though this heat is not lost to the body till the
warmed urine and faeces leave it. The amount lost in this
way has been calculated to be about 3 per cent, of the total
heat loss.

2. By the inspired air. The inspired air is taken in at
the temperature of the surrounding atmosphere, and contains
only a small amount of aqueous vapour. The expired air
has a temperature of about one degree lower than the body
temperature, and is saturated with waterj^ vapour. Heat is
therefore lost in respiration in two ways : 1st, in warming
the inspired air ; and 2nd, in the evaporation of large quan-
tities of water. These two sources of loss constitute about
20 per cent, of the total heat loss.

FATE OF FOODSTUFFS JN THE ORGANISM 505

3. By the skin. Here again the loss of heat is effected
in two ways. 1st. By radiation and convection. By these
means an interchange of heat takes place between the sur-
face of the body and surrounding objects, tending to cool the
body under ordinary circumstances when the external tem-
perature is below 98*4° F., or 37° C, or to warm the body
when the external temperature is higher than this, as during
the hot season in the tropics or in a Turkish bath. The
amount of interchange of heat between two bodies is directly
proportionate to the difference of temperature between them.
Thus the warmer the surface of the body in comparison with
that of surrounding objects, the greater will be the amount
of heat interchange, which in this case implies a loss of heat
to the body. Since very little heat is generated in the skin
itself, its temperature is intimately dependent on the amount
of blood flowing through it, and this in its turn on the con-
dition of the blood-vessels of the skin. When these are
dilated, there is a constant supply of warm blood from the
deeper parts of the body to the skin, which therefore is kept
warm and feels warm, both subjectively and objectively.
Hence dilatation of the blood-vessels of the skin, under normal
circumstances, brings about increased loss of heat. If, on the
other hand, the vessels are constricted, the small amount of
blood supplied to the skin rapidly becomes cooled, and the
skin is also cool, and the loss of heat small.

2nd. By the evaporation of the sweat. In the conversion
of water into watery vapour a large amount of heat becomes
latent. This principle is made use of in making ice, or in
cooling a bottle of water by surrounding it with damp cloths
which are exposed to a draught of air to facilitate evapora-
tion. If the secretion of sweat is small it evaporates as it
is secreted, and the skin remains dry. This is spoken of as
insensible perspiration. If the secretion be very copious it
may be formed faster than it can evaporate, and appears on
the skin as drops of sensible perspiration. The formation of
sensible perspiration depends then on two factors — the
amount of sweat secreted, and the rapidity of evaporation,
which latter again is dependent on the amount of saturation
of the surrounding atmosphere with watery vapour.

The loss of heat by the skin amounts to about 77 per cent,
of the total heat loss, and is therefore the most important of

506 PHYSIOLOGY

all the channels for the discharge of heat. The regulation
of the total heat loss is also effected chiefly by changes in
the loss through the skin. The nervous channels by which
this is carried out are the vaso-motor and the sweat nerves.
If the external temperature be below that of the body, the
loss by radiation and convection may be sufiicient to get rid
of the excess of heat produced. If however the external
temperature be higher than that of the body, radiation and
convection will serve only to warm the body still further,
and the sole loss of heat that can be effected is by the
evaporation of sweat, which is accordingly under such cir-
cumstances secreted in large quantities.

Often, especially after severe muscular exercise, radiation
and convection are not sufficient to carry oft" the excess of heat
produced, and hence there is a copious secretion of sweat
as well, even though the external temperature may be cool.

The evolution of heat is aided mider such circumstances
by two factors, viz. quickened and deepened respiration, by
which a greater volume of air is warmed up to the body
temperature at the expense of the body heat ; and quickened
heart-beat, by which more blood is driven through the dilated
cutaneous vessels, and so a rapid loss of heat at the surface
provided for.

In the dog, where there are no sweat-glands on the
general skin, and the loss of heat by conduction and radia-
tion is checked by the thick hairy coat, the quickening of
respiration is the most important means for getting rid of
the surplus heat produced in the body, and hence the pant-
ing and apparent distress of these animals in hot weather.

The extreme range of temperatures in a healthy man at
rest is between 36-1° C. and 37-8° C.

So perfect is the adaptation of the heat loss to the heat
production, that a man may travel from the poles to the
equator, may eat or fast, take exercise or rest, without causing
any lasting alteration in his temperature of 1° C, though
violent exercise may induce in many individuals a temporary
rise of temperature of 2° C.

The temperature of man, which varies from 97*8° F. to
98*4° F., undergoes certain diurnal variations, which are
important, since they are reproduced in an exaggerated form
in many fevers. The temperature is lowest between 2 and
4 a.m., and highest in the afternoon between 4 and 6 p.m.

FATE 0¥ FOODSTUFFS IN THE ORGANISM 507

Section G
THE NOEMAL DIET OF MAN

To maintain a man in perfect health it is necessary that
his food shall contain examples of the five different sorts of
foodstuffs — proteins, carbohydrates, fats, salts, and water.
The first three classes serve as sources of energy to the body.
Salts and water are equally necessary, although they cannot
serve as sources of energy.

Water forms an integral part of all living protoplasm ;
and the phenomena of life, even in the lowest organisms, are
dependent on an adequate supply of this substance. Apart
from its function as a constituent of protoplasm, it is also
essential as a medium for carrying the foodstuff's to the
tissues, and the waste products from the tissues and out of
the body. We have seen that water, in being discharged
from the body, has two functions — as a solvent of the effete
nitrogenous and other material contained in the urine, and
as a powerful means by which the excess of heat produced
in the body is dissipated. To supply this loss water must be
a constituent of the foodstuff's.

The exact part played by salts in the body we do not
know, although it has already been shown that the presence
of calcium salts is a necessary condition for two physiological
phenomena — the clotting of milk and of blood. It has been
shown moreover that a frog's heart will go on beating for
many hours if fed with a solution containing phosphates
and chlorides of potassium, sodium, and calcium, although,
if any one of these salts be absent, the heart soon comes to
a standstill. Of the salts present in the body and taken in
with the food, sodium chloride forms the largest quantity.
The presence of potassium and phosphates however seems to
be of more importance in the active phenomena of proto-
plasm, since these are found in largest proportions in organs
consisting chiefly of cells with very little interstitial sub-
stance. It will be remembered too that potassium and phos-
phoric acid are the leading base and acid present in muscle

508 PHYSIOLOGY

and in blood-corpuscles. An animal, if fed on a diet free
from salts, dies almost as quickly as an animal that is starved.
At an early period of life the human animal, as all mam-
malia, is fed exclusively on milk, and the composition of milk
agrees almost entirely with the ideal composition of the
normal human diet, that has been worked out by numerous
authorities as the result of many laborious experiments.
Thus it has been found that a man may maintain himself in
perfect health, neither gaining nor losing weight, on a diet
consisting of —

Proteins 100 grms.

Fats 100 „

Carbohydrates 240 „

Salts and water.

In cow's milk we find that for every 100 grms. of protein
we take in 107 grms. fat and 140 grms. carbohydrates.

In human milk, for every 100 grms. protein there are
170 grms. fat and 270 grms. carbohydrates.

The following table represents the average compositions of
human and cow's milk :

Human

Cow's

Gaseinogen and lactalbumen

2

. 4

Fats

. 2-75 ..

. 4

Lactose (sugar of milk)

. 5

. 4-4

Salts

. 0-25 ..

. 0-6

Total solids ....

. 10

. 13

Water

. 90

. 87

Milk when fresh is slightly alkaline or neutral. On
standing exposed to the air the lactose is converted by the
agency of micro-organisms into lactic acid. The milk hence
becomes sour, and the caseinogen is precipitated.

Human milk has a specific gravity of 1025 to 1035.

The 2Jroteins of milk consist of caseinogen and lactalbu-
men. Caseinogen, which forms by far the greater quantity^
is a complex protein belonging to the group of phospho-pro-
teins. From milk it may be precipitated by the addition of
acetic acid or weak mineral acid. When purified it forms
a snow-white powder, insoluble in water, but easily soluble in
dilute alkaline solutions, such as soda, ammonia, lime, or
baryta water. From these solutions it may be reprecipitated
by neutralisation. The purified caseinogen when moist has
the power of expelling CO^ from certain carbonates, and

FATE OF FOODSTUFFS IN THE ORGANISM 509

is therefore looked upon as a weak acid. In the milk,
caseinogen occurs in combination with calcium. Its power
of clotting with rennet ferment has been already described
(p. 323).

Lactalbumen, which resembles very closely serum albumen,
is present only in traces in cow's milk, but in much more
considerable quantities in human milk. The relatively smaller
amount of caseinogen in human milk probably accounts for
the fact that the clot produced by rennet in the latter is
flocculent, and does not form a firm compact mass as in cow's
milk.

Fats occur in milk in the form of minute droplets of
various sizes. It is the presence of these which gives to
milk its brilliant white appearance. If milk be allowed to
stand they rise to the surface, forming the layer of cream.
The droplets are probably prevented from running together
by being surrounded with a protein envelope, or perhaps
this is effected simply by the physical nature of the solution
of caseinogen in which they are suspended. If cream be
beaten or churned, this physical condition is overcome, and
the fat droplets run together to form a mass known as butter.
The fats of milk or butter consist of the glycerides of stearic,
palmitic, and oleic acids, with traces of the glycerides of
capric, caprylic, capronic, and butyric acids.

The carbohydrates are represented by lactose (Ci^H.jjO,,)
or milk-sugar. This is much less soluble in water than cane-
sugar, and is only faintly sweet. It reduces Fehling's solu-
tion, but does not reduce Barfoed's solution. It forms with
phenylhydrazine an osazone which is fairly soluble in water.
On boiling with dilute acids it takes up water and is con-
verted into equal parts of dextrose and galactose :

C.,H,,0„ + H,0 = C,H,A + CeH.A.

Dextrose Galactose

Under the influence of the lactic acid organism it is con-
verted into lactic acid : CioH.^Oi, + H^O = 4C.,H,;03. This
lactic acid is, like the acid of muscle, an ethylidene lactic acid,
CH3

CH(OH), but, unlike this, is optically inactive. The souring

COOH

of milk is due to this conversion of lactose into lactic acid.

510 PHYSIOLOGY

The salts consist chiefly of the phosphates and chlorides
of sodium, potassium, calcium, and magnesium. Of these
calcium is present in the largest quantities to supply the
material needed for the rapidly growing bones of the young
animal. The potassium occurs in far larger amount than the
sodium, as would be expected from what has already been
said concerning the part played by potassium in the functions
of living protoplasm.

Milk also contains small traces of iron in combination with
some protein body.

The food of the adult consists chielly of meat, eggs, cereals,
and green vegetables.

The following may be taken as an example of a complete
diet (Waller) :

Carijou

Nitrogen

[ 1 pound bread .

. 117 grms. ..

5-5 grms

Foundation - h pound meat

. 34 „

7-5 .,

1 ^ pound fat

. 84 „

—

/ 1 pound potatoes

. 45 „

1-3 „

i pint milk
Accessories , ^

, i pound CKgs

. 20 .,
. ].5 „

1-7 „
2

[^ pound cheese .

. 20 „

3

333 21

This diet is considerably more liberal than that given on
p. 508.

Meat consists of several animal tissues. Muscular tissue
forms the greater part of it, though it also contains white
fibrous tissue in the connective tissue and aponeuroses, and
some interstitial fat. There is also a greater or less quantity
of fat surrounding the muscles. Meat in its most general
sense therefore comprises proteins (myosin and albumen),
fats, collagen or (in cooked meat) gelatin, and minute traces
of carbohydrate, as glycogen or sugar. ^

Eggs consist of two parts, the white and the yolk. The
white is simply a solution of egg albumen, with a small
amount of globulin and ovo-mucin, enclosed in delicate

' Lean beef contains in every 100 parts —

Proteins ...... 18-36

Gelatiniferous substances . . . 1'64

Fat 0-90

Extractives 0-00

Ash 1-30

Water 7(v80

FATE OF FOODSTUFFS IN THE OEGANISM 511

membranes. The yolk contains a peculiar phosphorised
protein, vitellin, a large amount of fats, salts, and traces of
sugar and iron. The latter, as in the case of milk, is present
in a complex organic compound allied to the nucleo-proteins.
A hen's egg weighing 53 grms. (average weight) contains
31 grms. of white of egg (albumen and water with a small
amount of globulin), 16 grms. of j^olk, and 0 grms. of egg-
shell. A man would have to eat twenty eggs a day in order
to obtain the amount of protein given in the standard diet on
p. 508.

The vegetable articles of diet are distinguished from the
animal in containing a much larger proportion of indigestible
material, chiefly consisting of cellulose. This also encloses
much of the digestible portions of the vegetable, so that tliese
also pass out in the faeces undigested. On this account a
certain amount of vegetable food is of importance in the
normal dietary, since the indigestible residue increases the
bulk of the faeces, and aids the normal action of the bowels.

The cereals are the most important class of vegetable
foodstuffs. They include wheat, barley, rye, oats, maize, and
rice. Wheat-flour, out of which bread is made, contains pro-
teins, carbohydrates, and a small amount of fat (less than
2 per cent.). The proteins, forming about 12 per cent., are two
in number — a protein belonging to the class of globulins,
soluble in 10 per cent. NaCl, and an albumose. On treatment
of flour with water a change takes place in these proteins, and
the flour becomes sticky and ' doughy.' In the dough two
proteins are found — gluten, or vegetable fibrin, and a sticky
body, gleiadin, which is soluble in alcohol, and gives the
reactions of an albumose. The carbohydrates consist almost
entirely of starch, which forms about 70 per cent, of wheat-
flour.

Bread is made by moistening flour with water, so as to
form dough. This is mixed with some dough which has been
made previously, so that the diastase contained in the flour
has had time to act on the starch, converting this into dextrin
and maltose. The mixed doughs are then kneaded witli a
little yeast, and set in a warm place to ' rise.' By the action
of the maltase of the yeast, the maltose is converted into
dextrose, and this is decomposed by the yeast with the forma-
tion of alcohol and carbon dioxide. This latter forms little

512 PHYSIOLOGY

bubbles in the dough, causing it to swell up. The raised dough
is then baked. In the latter process the starch, exposed to
a temperature of 200° C. to 270^ C, becomes partly converted
into dextrin, and is therefore rendered soluble in water.

Green vegetables are chiefly valuable in the human dietary
owing to the large proportion of salts and cellulose in them.
Potatoes consist nearly entirely of starch, and contain very
little protein. Hence to support life by this means alone
very large amounts must be taken. It must be remembered
that starch-grains are enclosed in a series of cellulose enve-
lopes, and are therefore indigestible when raw. On boiling
the starch-grains swell, rupturing these envelopes, and the
opalescent semi-solution of starch thus formed is easily acted
on by the digestive juices.

518

CHAPTER XII

THE DUCTLESS GLANDS

Under this title have been grouped a number of organs, the
sole resemblance between which lies in the fact that we know
very little about them. Since however they seem to exert
important though obscure influences on the nutrition of the
body, they may be fitly discussed after the chapter on
metabolism. In many instances their functions seem to be
to furnish an ' internal secretion ' to the lymph or blood
which leaves them. This is almost certainly the case with
the thyroid gland, but the exact nature of the secretion or its
action is in all cases very difficult to determine. It may act
as an antitoxin to certain poisonous products of the normal
activities of the tissues, or as a necessary physiological
stimulus to the growth or the noi-inal functions of one or
a group of tissues.

The chief ductless glands are the spleen, thyroid, thymus,
and suprarenal capsules, but besides these, other glands, such
as the pancreas, ovaries, testes, have been thought to influence
the body by means of internal secretions. We have also to
mention the small bodies of unknown function such as the
pituitary body, the pineal body, the parathyroids, the carotid
and coccygeal glands.

The Spleen

This organ is similar in many respects to a lymphatic
gland. It is formed of a framework of connective tissue and
unstriated muscular fibres, in the interstices of which is con-
tained the sjylenic j)?f //;. This consists of a fine fibrillar net-
work, on the fibrils of which lie endothelial cells. The meshes
contain the cells of the splenic pulp, which are fairl}^ large
polygonal cells, and leucocytes. Just as in a lymphatic gland
the cellular elements of the tissues are bathed by the lymph

33

514 PHYSIOLOGY

which HowH through the gland, so m the spleen the walls of
the capillaries become discontinuous, and the blood is poured
out into the interstices of the tissue. The spleen is therefore
the only tissue in the body where the blood comes in actual
contact with the tissue-elements themselves. The blood from
the splenic pulp is collected into large venous sinuses, which
run along the trabeculge to the hilum, where they unite to
form the splenic vein. The arteries to the spleen are beset
in their course along the trabecule with small nodules of
lymphoid tissue, which are known as the Malpighian follicles.
It is evident that the blood must meet with considerable
resistance in passing through the close meshwork of the
splenic pulp. To ensure a constant circulation through the

Fig. 224.

Carotid

dog.8'5kllo all connections with spllen

severed except one artery & vein *

0 pressure

Plethysmogiapliic tracing of spleen (upper curve) from dog, showing
the spontaneous contractions of this organ (reduced from a tracing
by Schafer).

gland, we find that the muscular tissue of the capsule and
trabeculse has the property of rhythmic contraction. If the
spleen be enclosed in a plethysmograph, or splenic oncometer,
and its volume be recorded by connecting this with the
oncograpli, it will be seen that it is subject to a series of
large, slow variations, each contraction and expansion last-
ing about a minute, and recurruig with great regularity
(Fig. 224). Superposed on these large waves are seen the
smaller undulations due to the respiratory variations of the
blood -pressure, and on these again the little excursions
corresponding to each heart-beat. The contractile power of
the si)leen is under the control of the nervous system, and

THE DUCTLESS GLANDS

515

a rapid contraction may be induced by stimulation of the
splanchnic nerves.

Functiuns of the Spleen

The structure of this organ suggests that the splenic
cells must exercise a constant influence on the blood which
surrounds them, and that this influence is not purely of ii
chemical nature. In the liver and kidneys, which exercise
so powerful an effect on the composition of the blood
passing through them, the proper cells of the organs are

Fiu. 225.

Cells fi'oiii a bciaping ol the spleen (Kollikei|. A, splenic pulp-cell
containing red blood-corpuscles, b (k = nucleus) ; B, leucocyte
with polymorphous nucleus; C, pulp-cell containing disinte-
grated red corpuscles ; D, lymphocyte ; E, giant-cell ; F,
nucleated red corpuscles ; G, normal red corpuscle ; H, multi-
nuclear leucocyte ; J, eosinophile cell.

separated from the blood-stream by the capillary wall.
Microscopic examination of the cells of the splenic pulp
shows us that these are full of particles of brown pigments
or fragmeiits of red corpuscles (Fig. 225). In many cases
of infectious disease, such as recurrent fever, the splenic
cells are observed towards the end of the attack to be full of
the organism— spirillum — which is the cause of the disease.
In fact, these cells are so arranged that they can take up
solid particles held in suspension in the blood -plasma. We
must indeed look upon the spleen as the great blood-filter,
purifying the blood in its passage by taking up particles of
foreign matter and effete red corpuscles. The process ot

516 PHYSIOLOGY

phagocytosis, which was described under Inflammation, is in
the spleen a normal occurrence.

A function has also been assigned to the spleen m the
formation of red blood-corpuscles, but the evidence is not
sufficient to determine whether such a process occurs
normally.

Chemical analysis of the spleen reveals the presence of a
large number of what are called extractives, such as succinic,
formic, butyric, and lactic acids, inosit, leucine, xanthine,
hypoxanthine, and uric acid. There is also a protein allied
to alkali-albumen, combined with iron, as well as several
pigments probably derived from the ha>moglobin of the red
corpuscles destroyed by the cells of the splenic pulp. The
fact that, in cases where the spleen is pathologically enlarged
as in leucocythccmia, the uric acid in the urine is largely
increased, pouits to a connection between the spleen and the
formation of uric acid in the body. The numerous extrac-
tives which are formed probably owe their origin to the
destructive changes effected on the effete constituents of the
blood by the agency of the splenic pulp-cells.

The Thymus Gland

The thi/Diiis is a body situated in the anterior medias-
tinum; it is richly supplied with blood-vessels, and is com-
posed of modified lymphoid tissue, which is peculiar in con-
taining epithelial remnants known as Hassall's corpuscles,
and derived from the epithelium of the branchial clefts of
the embryo. It is only of importance in early life ; it is
relatively large in the fa-tus, and increases in size during the
first two years after birth. It afterwards atrophies, and in
adult life is represented by a small collection of adipose
tissue. Of its function we know nothing. It is supposed
to be of importance in the formation of blood in the young
animal. From the thymus a body can be extracted (tissue-
fibrinogen) which, injected into the veins of an animal, causes
intravascular clotting. This fact however does not throw any
light on the normal functions of the gland, since a similar
body may be extracted from almost any organ that is rich
in cells.

THE DUCTLESS GLANDS

517

The Thykoid Gland

The thyroid was probably at one time in the history of
the race a secreting gland in connection with the alimentary
canal. In the developing animal it is formed, like the
pancreas and liver, as an outgrowth from the fore-part of the
alimentary canal. Long before the end of fcetal life how-
ever, its duct becomes obliterated, and each acinus becomes
closed. In the adult it consists of two oval lateral lobes
lying on each side of the upper part of the trachea and
united across the front of this tube I)}'' a middle lobe or
isthmus. Each lobe is made up of a number of vesicles of
various sizes imbedded in connective tissue, which carries

Fig. 22G.

Section of thj'ioifl ^laml of dofj', (Swale Vincent.)

the blood-vessels, nerves, and lymphatic vessels of the gland.
The vesicles are lined by a single layer of cubical epithelium
and filled with a peculiar hyaline material known as the
colloid substance (Fig. 226). In some cases this colloid
material can be seen to extend between the lining cells into
a neighbouring lymphatic vessel. The same path is often
taken by artificial injections, so that it seems probable that the
lymphatics may l)e regarded as the efferent ducts of the gland.

The colloid substance contains a nucleo-albumen, and a
substance known as thyroiodin, owing to the fact that it
contains iodine in organic combination with protein.

Although its primitive function of secretion is lost, it is

518 PHYSIOLOGY'

still of the utmost importance in the metaholism of the body.
If the thyroid gland be totally extirpated in young animals,
the operation is followed after a short time by severe sym-
ptoms, consisting of fibrillar twitchings and spasms of the
muscles, attended with weakness and stupor. These effects
usually terminate in the death of the animal. In man it
has been shown that a disease (myxcedema) occurring in adult
life is dependent on the atrophy of this gland. The main
symptoms of this disease are generally stupidity and slowness
of speech of the individual, slow pulse, subnormal tempera-
ture, and a thickening of the subcutaneous tissues, so that
the patient at first sight looks dropsical. All the processes
of the body are slowed. The nitrogenous metabolism is
diminished, as shown by the lessened outflow of urea ; men-
struation in women ceases, the hair falls out, and the skin
becomes dry and harsh.

Cretinism is also associated with absence of the thyroid
gland. A cretin remains a childish idiot all his life, and
preserves his childish appearance. In these cases small
fatty tumours are often found on each side of the neck just
above the clavicle. We are absolutely unable to explain
the connection of these manifold symptoms with the absence
of the thyroid gland. There seems to be no doubt however that
they are due to the absence in the body of some substance
which is normally supplied by the activity of the thyroid
gland, i.e. an internal secretion, since the symptoms pro-
duced by the extirpation or atrophy of the gland may be
relieved by the administration of the fresh or dried glands of
sheep. It is interesting to note that administration by the
mouth is as effective as subcutaneous injection, showing that
the active substance, whatever it may be, is easily absorbed
by the stomach and is not destroyed by digestion.

In healthy individuals thyroid extract is found to in-
crease the output of urea, by causing increased tissue waste.
Hence it has been used as a remedy for obesity. Large
doses cause increased frequency and force of the heart-beat,
and it has been thought that the symptoms of exophthalmic
goitre, in which an enlarged thyroid is associated with pro-
trusion of the eyeballs and great acceleration of the heart,
may be due to an excessive production of the specific secre-
tion of the gland.

THE DUCTLESS GLANDS 519

The Parathyroids

These are small oval or rounded bodies about 5 to 12 mm.
long, situated near the hinder border of each lobe of the
thyroid, and in some cases imbedded in the thyroid itself.
They consist of elongated groups of polygonal cells, ap-
parently epithelial, bound together by connective tissue,
which also forms a capsule to the gland. They are well
supplied with blood-vessels. Their mode of development as
well as their functions is unknown. According to some
authors they are at least as important for the normal life of
the organism as the thyroid itself, and it has been suggested
that the nervous symptoms (muscular twitchings and con-
vulsions), which follow total extirpation of the thyroid in
animals, are really due to the simultaneous removal of the
parathyroids. According to this view, if the parathyroids
were left intact, removal of the thyroid in animals would
always give rise to a condition analogous to that of myx-
cedema in man. It is probable, however, that the parathyroids
represent merely immature thyroid tissue, and have therefore
a similar function.

The Pituitary Body

This is a small body filling up the sella turcica of the
sphenoid bone. It consists of two lobes, a posterior of
nervous tissue, derived from the floor of the third ventricle
with which it is connected by the infundibulum, and a larger
anterior lobe formed by an ingrowth of the epiblast of the
buccal cavity. This lobe consists of alveoli lined with epi-
thelium and sometimes containing a material resembling the
colloid of the thyroid, as well as solid masses of epithelial
cells, all enclosed and bound together by a vascular connec-
tive tissue. The functions of this body are unknown. Its
deep protected position has so far militated against its suc-
cessful extirpation. It has been found however that in a
large proportion of the cases of acromegaly (a rare disease
characterised by overgrowth of the bony tissues of the face and
extremities) the pituitary has been the seat of sarcomatous
enlargement. It is suggested therefore that this body secretes
a substance which is essential in some way or other for the

520 PHYSIOLOGY

]n'oper nutrition and growth of the bones. The posterior lobe
has been shown to yield a sii])stanee having a marked diuretic
efi'ect.

The pineal gland represents the remains of a ],)rimitive
dorsal invertebrate eye. So far as we know, it is at present
only of historical interest.

The Surr.AP.ENAL Capsules

These are small triangular bodies situated one above
each kidney. They consist of cortex and medulla, the cortex
composed of groups and columns of closely packed polygonal
cells, while the cells of the medulla are more irregular in
shape with a reticular arrangement. The medulla presents
the openings of a number of large veins. Its cells contain a
substance which stains brown with chromic acid and its salts.

Here again pathology has taught us more than physio-
logical research. The disorder known as Addison's disease,
and distinguished by the three cardinal symptoms of extreme
weakness, vomiting, and pigmentation of the skin (which
acquires a bronzed colour), was recognised by its discoverer to
be due to atrophy of the suprarenal capsules. The explana-
tions, which were formerly brought forward of the connec-
tion of these phenomena with the extirpation or destruction
of the capsules, may be classified into chemical and nervous.
The suprarenals have a twofold origin, their medullary part
being derived from the sympathetic nervous system, and
their cortical part from the surrounding mesoblast. The
supporters of the chemical theoiy based their views on the
fact that derivatives of lia3moglobin are to l)e found in these
organs, and they therefore looked upon them as chemical
depots for the removal or destruction of the waste pigmentary
products. Retention of these in the blood gave rise to
poisoning symptoms, and to deposition of pigment in the skin.
As upholding the function of these bodies in influencing
nutrition through the nervous system, widespread degenera-
tions in the central nervous system were described after their
extirpation in animals. Subsequent investigations however
have failed to confirm these results.

It seems more probable that the suprarenals, in part
at anv rate, owe their importance to the production of an

THE DUCTLESS GLANDS 521

internal secretion, \Yhich they pour into the blood bathing
their cells. From the medulla of the suprarenal glands a
substance, adrenalin, can be extracted which in minimal doses
produces most marked effects. The chief results of the
injection of this substance are marked rise of blood-pressure,
due to constriction of all the arterioles of the body, and
increased strength of the heart-beats. The active principle
is not a protein, but is diffusible. It is a derivative of pyro-
cateehin, from which body it may be prepared synthetically
(Dakin). It acts on nearly all muscular tissues, producing
a lengthening of the contraction of skeletal muscle as well as
the effects on heart and blood-vessels just described.

As a rule its injection causes great slowing of the heart-
beats. If however the vagi be cut, this effect does not
appear and the arterial pressure rises to two or three times
its previous height. This effect is not abolished by previous
section of the cord or the splanchnic nerves. This slowing
of the heart can be probably regarded as directly occasioned
by the great rise of blood-pressure, and only indirectly by
the adrenalin. It is interesting to note that not all muscular
tissues are thrown into action by adrenalin. In some cases
the muscle may be inhibited and relaxed. In fact, in every
case that has yet been investigated, the action of adrenalin
on muscle is identical with that produced by stimulation of
the sijmjmthetic nerve supply to the tissue. Thus we may
get, besides the effects already mentioned (viz. vasocon-
striction and augmentation of heart-beat), dilatation of the
pupil, erection of hairs, relaxation of intestinal wall and of
bladder, flow of saliva, etc. This similarity of the effects of
injection of adrenalin to those produced by general stimu-
lation of the sympathetic is probably connected in some way
with the development of the medulla of the suprarenals as
an outgrowth of the sympathetic system itself.

It is supposed that this substance is being constantly
produced and distributed over the body, its absence being
responsible for the extreme prostration and muscular weak-
ness which are so marked in Addison's disease. The pigmenta-
tion and vomiting of this disorder still remain to be accounted
for, nor have we yet been able to assign any function to
the cortex of the suprarenals, forming the greater bulk of
these glands.

522 PHYSIOLOGY

CHAPTER XIII

SPECIAL SENSES

Section 1
ON SENSATION IN GENERAL

We must now consider the means by which the individual
is made aware of the events occurring in the outside world,
the means by which his environment acts upon him. This
subject is comprised in the physiology of the special senses.

All the organs of special sense contain specially modified
epithelial cells, derived from the epiblastic layer of the
embryo, or processes of these cells. From the deeper side
of these cells, processes or nerve-fibres grow into the central
nervous system ; these l)reak up into fine arborisations of
fibres which come into close contact with other cells or fibres,
and so make functional connection with the nerve-tracts
which serve as paths to the higher centres, or to the cells
which preside over the movements of certain muscles.

In some cases, such as the olfactory mucous membrane
(Fig. 227, a), the sensory cell lies close to the periphery, and
is the immediate recipient of the physical stimulus which it
has to transmute into a phj'siological nerve impulse.

In the auditory organ the special sense-cell seems to be
represented by the bipolar cells of the spiral ganglion.
These (Fig. 227, b) send one process towards the organ of
Corti, where it terminates in fine filaments among the hair-
cells, and one running in the auditory nerve towards the
medulla.

In other cases the sensory cell may lie still further away
from the sensory surface. Thus, in the skin, the sensory
filaments ramifying in the epidermis represent the terminal
arborisation of the process of a cell in a posterior root gan-
glion. This process joins by a T-shaped junction with

SPECIAL SENSES

523

another process whieli runs centralwards and terminates in
fine filaments in the grey matter of the spinal cord and
medulla (Fig. 228, a).

Fm. 227.

: i\^

A. Connections of olfactory cells with olfactory lobe.
B. Auditory sense-organs.

The peripheral terminal filaments of these nerve-cells may
either end freely among ordinary nndift'erentiated epithelial
cells (as in Fig. 228, 15), or may he closely applied to specially

Fi(i. 228.

:^?}y>-^--

A. Connections of gustatory fibres. (Taste-bud.)
B. Nerve-ending in skin or corneal epithelium (probably pain-fibres),

modified epithelial cells. Such special sensory epithelium
is found in the taste-huds (Fig. 228, a) and in many parts of
the skin (tactile corpuscles).

524 PHYSIOLOGY

In every case a sensation, whether of heat, light, sound,
or touch, is caused l)y some movement of molecules or masses
occurring in the outside world, and the function of the special
sense-organs is to be acted on by these movements and to
convert them into a nerve impulse, which ascends an afferent
nerve towards the spinal cord or brain. Arrived here, it
gives rise to some form of reflex action, which may be un-
conscious or conscious. In the latter case we become aware
of a sensation of light, heat, or sound, etc. Now it is found
that if the nerve-fibres coming from a special sense-organ be
stimulated artificially by electric shocks or in any other way,
we get a sensation similar in kind to that wdiich would occur
if the sense-organ itself were stimulated in the normal way.
Thus stimulation of the optic nerve gives rise to the sensa-
tion of light ; of the auditory nerve, to one of sound ; of
the nerves of smell or taste, to these respective sensations.
This fact, which has not been proved experimentally for all
sensory nerves, is yet so general that it has been formulated
as a law, known as Miiller's law of specific irritability. This
law merely states that every sensory nerve reacts to one form
of stimulus and gives rise to one form of sensation only ; that
every sensory nerve, in fact, minds its own business.

Most important in connection with the physiology of the
senses is the fact that in some cases we are able to 'project
the stimulus, and recognise it as coming from an object at
some distance from us. We can also localise the stimulus,
and recognise what part of the body is being stimulated, or
the position of the body in space from which the stimulus
arises.

There is a certain proportionality between the strength
of the stimulus and the intensity of the sensation produced ;
that is to say, a stronger stimulus will produce a stronger
sensation. As the stimulus is increased, the amount of
additional stimulus required to produce any appreciable in-
crease of sensation is also increased. Thus we can dis-
tinguish the heavier of two weights — -one of B9 oz., the other
of 40 oz. ; we cannot however between 39 lbs. and 39 lbs.
1 oz., but must add a whole pound to the 39 lbs. in order to
appreciate a distinct difference. This fact is known as
"Weber's law, which runs thus : The increase of stimulus
which is required to produce distinct increase of sensation

SPECIAL SENSES 525

always hears the same ratio to the whole stimulus. In the
example above given this ratio is 1 to 40 (muscular sense).
In the case of the pressure or tactile sense the ratio is 1 to 30.
This law holds good only within certain limits, and fails
when the stimuli are very strong.

Besides the five senses that are commonly recognised —
of sight, hearing, touch, taste, and smell -physiologists
reckon the senses of heat and cold, pain, the muscular sense,
and the sense of equilibrium or static sense. The indefinite
sensations of hunger, thirst, weariness, etc., defy accurate
physiological analysis.

526 PHYSIOLOGY

Section 2
CUTANEOUS SENSATIONS

The whole surface of the body is susceptible to stimuli,
which may give rise to sensations of touch, heat, cold, or
pain ; and it seems probable that these different kinds of
sensation are served by different sets of nerve-fibres. It is
very difficult however to assign to each form of end-organ
that has been distinguished by anatomists its proper function.
Thus we find in the subcutaneous tissues the Pacinian
corpuscles as well as the various kinds of end-bulbs, and the
rich end-arborisations on the fibrous tissue bundles known
as Ruffini's endings. In the papillary layer of the corium
we find Meissner's corpuscles (the tactile corpuscles, Fig. 229).
In the root-sheaths of the hairs there is a rich meshwork
of nerve-fibrils, especially well marked in the tactile hairs.
Finally in the epidermis there is the intra-epithelial plexus
of non-meduUated nerve-fibrils, as well as the fibres which
end in connection with specially modified epithelial cells, the
so-called tactile cells. Although we regard Meissner's cor-
puscles as essentially tactile, there is no doubt that the same
functions must be served by the brushlike nerve-endings
surrounding the hair follicles. On the other hand, the intra-
epithelial plexus in the cornea must set up pain impulses, since
these are the only sensations which result from stimulation
of the cornea.

Tactile Sensations

By means of these sensations we are able to judge of the
shape, size, and consistence of bodies in contact with the
skin. Thus by feeling we can tell that a body is hard or soft,
rough or smooth, single or multiple, etc. These conclusions
however are not determined by the tactile sense alone, but
are dependent on a numl)er of other centripetal impulses,
especially those concerned in the muscular sense or sense of
movement.

On careful testing of the tactile sense, in minute spots
over a given area of skin, it is found that the sensibility is

SPECIAL SENSES

527

not evenly distributed over the whole surface, but that the
special tactile nerve-endings occur at definite spots, between
which a strictly localised stimulus (as by the point of a hair)
evokes no tactile sensation. These spots can also be mapped
out by means of localised electrical stimulation, and it has
been found that, using discontinuous stimuli, the sensation
produced is also discontinuous so long as the rate of interrup-
tion of the current does not exceed 130 per second.

The tactile spots are especially marked round each hair
follicle, but a few spots also occur between the hair follicles,

Tactile corpuscle from a papilla of the skin (Kanviei). n, two nerve-
fibres passing to the corpuscle ; a, a, varicose ramifications of the
axis-cylinders within the corpuscle.

and of course are thickly distributed over the palmar side of
the hand and fingers.

Every tactile sensation has what is termed its local sign,
i.e. we are able to localise the exact point at which the
stimulus is applied to the skin. This power of localisation
is intimately connected with the sense of movement and may
be impaired by lesions affecting apparently only the efferent
side of motor reactions. Intimately connected with the localisa-
tion is the power of discrimination of stimuli as single or
multiple. Thus if two points tipped with cork, a quarter of
an inch apart, be applied to the tongue, they are perceived
as two points ; applied to the skin of the back they give rise

528 PHYSIOLOGY

only to one sensation. The following tal>le shows the dis-.
tances which two points must be apart in order to cause two
distinct sensations.

Tip of tongue ........ 1 mm.

Palmar surface of haml, teraiiii-il phalanx . . 2 „

Lip 9 „

Front of forearm . . . . . . . 15 „

Forehead 23 „

Back of hand 30 „

Neck, back, arm, and thigh .... 50-70 ,,

As we shall see later, tactile sensations are of immense
importance in the retlex maintenance of equilibrium and the
performance of co-ordinated movements.

Temperatitre Sense

Our subjective feeling of warmth or cold depends not on
the temperature of the body itself, but on the temperature (jf
the skin, where the special sense-organs are situated. It has
been shown that in the skin there are two kinds of nerve-
endings for temperature, which are excited respectively by
heat or cold. Thus if a small metallic pencil, kept at body
temperature by a stream of warm water through it, be moved
gently over the skin, and the attention be directed on the
sensations evoked, it will be found that while at some points the
sensations are indifferent or merely tactile, at certain points
the pencil may feel uncomfortably hot. The points where
this is found to be the case are mapped out as heat spots.
By using a cool pencil a series of cold spots may be mapped
out in the same way, and it is found that this series does not
coincide with the first. Fig. 230 shows the distribution of
the heat and cold spots.

It is worthy of note that the cold spots are much more
widely distributed than the warm spots, and this difference
is especially marked in those portions of the body which
are normally covered with clothes. The hand is relatively
insensitive to changes of temperature, and it may be observed
as a general rule that in those regions where the tactile sense
is best developed, the temperature sense is least developed.
It is evidently of more importance to the organism that it
should feel discomfort l)y a fall of temperature than that it

SPECIAL SENSES

529

should by a rise of temperature, as shown by the prepon-
derance of social contrivances, sartorial and otherwise, for
maintaming the body temperature over those for cooling the
body. At a certain temperature varying in different parts of
the body, the sensation of ' warm ' undergoes a qualitative
change and becomes that of ' hot,' and this change occurs
some degrees lower than the temperature at which the
threshold of pain is reached. It has been shown that, if the
pencil used for testing the temperature sense is heated to
45" C. or over, it excites also the cold spots. To this excita-
tion of cold spots is probably due the shudder which frequently

Fig. 230.

Cold spots. Heat spots.

Heat and cold spots on part of palm of light hand. The sensitive
points are shaded, the black being more sensitive than the lined
and these than the dotted parts. The unshaded areas correspond to
those parts where no special sensation was evoked. (Goldscheider.)

occurs on entering a hot bath, and it seems that the feeling of
' hot ' is really due to the simultaneous stimulation of both
warm and cold spots. Thus if two adjacent spots of the skm
be excited by a double pencil, half of which is warm and the
other half cold, a sensation of heat is produced, whereas if
the cold pencil be removed, the remaining sensation is only
one of w'armth.

Pain

Over-excitation of the nerves of the skin, whether by
cuttmg, electrical stimuli, excessive heat or cold, produces a
sensation of pain. Hence it has been thought that pain is
merely an hypertrophied tactile or temperature sensation ; but

34

530 PHYSIOLOGY

there are arguments which tend to show that pain is a
distinct sense, and subserved by a distinct set of nerve-tibres.
Many cases of disease occur in which the patient can feel
the slightest touch, but is quite insensitive to pain. In other
cases, in which the tactile sense is deficient, the pain sense
may be exalted. We can moreover map out on the surface of
the skin pain spots similar to the heat and cold spots men-
tioned above. In certain regions of the body only one or
more of these sensations may be present. Thus the surface
of the cornea is sensitive only to painful impressions, that
of the glans penis only to sensations of pain and cold,
ordinary tactile and heat sensations being almost entirely
absent.

Direct stimulation of the trunk of a nerve going to the
skin gives rise only to a sensation of pain, whatever may
be the nature of the stimulus. Thus plunging the elbow
into a freezing mixture excites the ulnar nerve, and causes a
sensation of pain which is refei'red to the ring and little
iineers.

SPECIAL SENSES 531

Section 3
SENSATIONS OP MOVEMENT AND POSITION

Under the above heading we may group a number of sen-
sations which arise in special sense-organs in various parts
of our body, in consequence of changes in these parts them-
selves, and are not directly occasioned by stimuli, arriving
at the surface of the body from without. As examples we
may mention those sensations by which we are able to
tell the position in space of our body, and the relative
position of its various parts, besides the extent, force, and
direction of movements of any part, whether passive or
active. Although in tliemselves indistinct and dilhcult of
analysis, these sensations are of the utmost importance in
qualifymg other sensations, especially those of touch and
sight, and in imparting to these sensations the properties
which lead us to infer the position and extension in space of
the object from which the stimuli arise.

These sensations may be divided into two main groups —
the muscular sense and the static sense.

Muscular Sensatio)if>

This term is applied to those sensations by which we
know the position of our limbs, the extent to and the force
with which they have been moved. Many authors have
ascribed an important part in this knowledge to the so-called
sense of innervation, i.e. a sense of the actual energy which is
being discharged from the motor cells of the central nervous
system to the muscles, and have thought that when we raise a
weight we judge of its amount, not by the degree of stretching
of the muscle or pressure on sensory nerves in the muscle,
but by the amount of force we voluntarily put out to raise
the weight. The fact however that we can judge of weights,
when the muscles are made to contract by electrical stimuli
and not by voluntary impulses, shows that this sense is in
large part, if not entirely, peripheral. It is liowever very
complex in nature and is served by a whole array of different
end-organs in the skin, joints, tendons, and muscles. The

532

PHYSIOLOaY

muscles themselves are known to be well supplied with
aft'erent nerves. Stimulation of the central end of a mus-
cular nerve may reflexly excite or inhibit movements of other
muscles. Sherrington has shown that, after section of the
motor roots, over one-third of the fibres in a muscular nerve
remain undegenerated, proving their connection with the
posterior root ganglia. The sensory nerve-endings in the
muscle are represented partly by the tendon nerve-endings,
and partly by the muscle-spindles.

The former are richly branched end-arborisations of
nerve-fibres on the surface of the tendon bundles. The
muscle-spindles consist of one or more muscle-fibres, often
continuous with normal fibres, enclosed in a sheath composed
of several layers of fibrous tissue with intervening lymph-
spaces. One or more nerve-fibres pierce this sheath and.

Fig. 231.

A neuro-muscular spindle of the cat (llutlini). c, capsule ; pr.c,
piimaiy ending ; a.e, secondary ending ; pl.e, plate ending (all these
are probably sensory in function).

after making many spiral turns round the muscle-fibres,
branch freely and terminate in little knobs on the surface of
the fibres. The cross-striation of the muscle-fibres within the
spindle is but faintly marked. It is evident that the con-
tinuity of these sense-organs with the contracting muscle
ensures in the best possible way that the organs should be
atiected by the slightest change of tension of the contracting
muscle, and should transmit information of the state of
tension to the central nervous system.

These organs, together with the special nerve-endings
found on the tendons, are of importance in judging and con-
trolling the force and extent of active movements. On the
other hand our judgment of passive movements is largely

SPECIAL SENSES 533

determined liy afferent impulses wliich arise in the sensory
organs of the joints. It is evident that our sensations of
resistance, and therefore our whole conception of force, power,
and effort, are dependent on the tension of contracting muscles
and on the muscular sensations thereby evoked.

Our knowledge of the position of our limbs depends chiefly
on the complex of sensations which arise in the end-organs
of the skin and su])cutaneous tissue and the joints. ]\[uscular
sensations appear here to play but a subordinate part.

We shall later on have to refer to the importance of these
afferent impulses for the carrying out of normal movements.
We need here only mention that, in the absence of guiding
afferent impulses, no co-ordinated muscular contractions are
possible. Thus disease of the sensory nerves of the muscles
of the legs or of the afferent tracts of the spinal roots and
cord, such as occurs in tabes dorsalis, gives rise to the well-
known ataxj'', in which there is an entire absence of co-
ordination between the contractions of the different muscles
of the lower extremities. In walking, the leg is first raised
too high and is then brought down again on the ground with
a jerk. In the later stages of the disease, inco-ordination is
so marked that with the greatest effort the patient is unable
to move himself along, the muscles contracting violently and
in no regular sequence when he attempts to walk. If the
posterior roots of the hind limbs of a dog be divided, he is at
first unable to stand on his forelegs, and in trying to move
forward simply drags the apparently paralysed limbs after
him. Later on the dog learns to walk normally, but in this
case he has simply replaced the normal afferent impressions
from skin, joints, and muscles by visual sensations. If he be
painted with luminous pamt, and placed in a dark room where
his visual sensations are absent, the paralysis in his hind limbs
will be seen to l)e as marked as on the day succeeding the
operation. In the same way division of the posterior roots of a
fore-limb of a monkey causes paralysis of the liml) which, for
the finer movements of the hand and fingers, is permanent.

In the judgment of weights, cutaneous impressions take
little part. It has been found that the smallest appreciable
difference is about ~._^ of the whole weight — a proportion
which holds good in the case of the arm for all weights
between 0 and 6,000 grams.

5B4 PiiYsroLodY

The Static Sense or Sense of Posit km

Deeply buried in the bones of the skull and in close rela-
tion to the auditory end-orf^an is a special sense-organ whose
function it is to guide by its impulses the position of the
head and therefore of the rest of the body, and l)y these
impulses to arouse sensations by which we are informed of
the position of the head as well as of the direction and extent
of movements, active or passive, which the head may undergo.
This sense-organ is formed by the endings of the vestibular
nerve in the three semicircular canals and in the utricle and
saccule of the internal ear. This, which is formed in the
embr3^o by an involution of the epiblast and at first forms a
simple sac lined with epithelium and lying under the surface
of the skin, later becomes modified hj outgrowths in various
directions to form a complex membranous tube lined })y
epithelium and containing a fluid — the endolymph. This
membranous labyrinth is contained within a l)ony tulje — the
osseous labyrintli, which it does not wholly fill, being separated
from the bony wall over the greater part of its extent by
a fluid — the perilymph. The bony labyrinth consists of a
cavity — the vestibule, communicating by the fenestra ovalis
with the tympanic cavity externally, and with the cochlea
and auditory sense-organ anteriorly. The vestibule contains
two sacs, the utricle and saccule, the latter being in com-
munication with the spiral prolongation, which forms the
canalis media of the cochlea and is connected with hearing.
Behind the vestil)ule is in communication with the semi-
circular canals, three bony tubes lying in planes at right
angles to one another and opening into the vestibule by five
apertures, one aperture being common to two tubes. These
canals are named respectively the external or horizontal, the
anterior or superior vertical, and the posterior vertical
canals. Within these bony tubes, and separated from them
by the perilymph, are three membranous canals, each of
which has a dilatation or ampulla at one end, and all com-
municate with the utricle ; all these parts being developed
from the primitive auditory vesicle. In the ampulla are
situated the ultimate terminations of the vestibular division
of the auditory nerve (Fig. 2B2\

When these canals are injured definite disturbances of

SPECIAL SENSES

535

equilibrium are produced. Thus if in a pigeon the hovizontal
canal be divided, the head is thrown into a series of oscil-
lations in a horizontal plane, which are intensified by section
of the corresponding canal on the opposite side, so that the
animal may fall down.

After section of the posterior vertical canals the forced
movements are in a vertical plane, and the animal tends to
turn somersaults head over heels. After section of the

Fig. 232.

End-organ of vestibular nerve in ampulla of semicircular canal
(' crista aconstica ').

superior vertical canals the movements are still in a vertical
plane, and the animal tends to turn somersaults l)ackwards.
After destruction of all the canals on both sides the disturb-
ances of equilibrium are most pronounced and complicated.
The animal can neither stand nor tly, nor maintain any
fixed attitude, but is constantly executing somersaults, and
moving about so violently and incoherently that it is necessary
to pad its cage to prevent it killmg itself.

536 PHYSIOLOGY

After some months these disorders graduall}^ dis.appear,
and the animal learns to guide its movements by sensations
of touch and sight alone. But they are instantly brought
back in all their severity if the eyes be bandaged so as
to deprive the co-ordinating centres of the guiding visual
sensations.

It will be noticed that the semicircular canals on each
side are in three planes at right angles to one another, and
it is probable that we learn the positive movements of our
body with regard to the three dimensions of space by means
of impressions from the ampullary endings of the vestibular
nerve. These impressions are caused by the varying pres-
sure of the endolymph on the ampullary dilatations of the
semicircular canals.

Thus a sudden turning of the head from left to right
will cause movement of endolymph towards, and therefore
increased pressure on, the ampullary nerve-endings of the
left horizontal canal, and movement of endolymph away
from, and therefore diminished pressure on, the correspond-
ing ampulla of the right side. In this way, for movement in
any given plane, the two corresponding semicircular canals
of the two sides are synergic, and unite in sending impulses
which guide the equilibrating centres, and inform us of the
position of our head in space. ' One canal can be affected
by and transmit the sensation of rotation about one axis in
one direction only ; and for complete perception of rotation
in any direction about any axis six semicircular canals are
required in three pairs, each pair having its two canals
parallel (in the same plane), and with their ampulla? turned
opposite ways. Each pair would thus be sensitive to any
rotation about a line at right angles to its plane or planes,
the one canal being influenced by rotation in the one direc-
tion, the other by rotation in the opposite direction.' ' The
two horizontal canals are in the same plane, and the posterior
vertical canal of one side is in the same plane as the superior
vertical of the other (Fig. 233).

In the pigeon it is possible to cause a movement of fluid
in any desired direction in one of the canals. For this pur-
pose one bony canal is exposed and plugged in the middle of
its course as a dentist stops a tooth. The bony^ wall is then

Cinm-Brown.

SPECIAL SENSES

537

removed immediately in front of the stopping and a small tube
fixed on the head l)y means of plaster of Paris, in such a
position that a blast of air from a rubber-ball connected by a
flexible tubing with the first tube can be directed on to the open -
ing in the canal, so as to set up a current of endolymph in the
membranous canal. It is found invariably that the animal
responds to each mechanical stimulus produced in this way,
with a movement in the head and eyes in the same direction
as the current of endolymph, and in the same plane as the
semicircular canal involved.

These reflex movements of head and eyes are the invari-
able result of movements set up in the endolymph, and occur
equally well in the absence of the cerebral hemispheres. If

Fm. 238.

Diagram of semieirculav canals to show their position in three planes
at right angles to one another. It will be seen that the two hori-
zontal canals lie in the same plane (e), and that the superior
vertical of one side (a) is in the same plane as the posterior vertical
(p) of the other side (from Esvald).

an animal or man be placed on a turntable and rotated, his
first tendency will be to turn his head and e^^es in the opposite
direction to that of rotation. If the rotation be continued, the
endolymph gradually takes up the movement of the surround-
ing parts of the head, and if the eyes be closed, no movement
of head or eyes is observed. If now the rotation be stopped,
the endolymph will tend to go on moving, and the effect
will be the same as if a movement of rotation were suddenly
begun in the opposite direction. Head and eyes will now be
turned, without any voluntary impulse, in the direction of the
previous rotation and in consciousness there will be an actual
sensation of rotation in the opposite direction. This sensation
is in opposition to the sensations derived from other parts.

538 PHYSIOLOGY

and hence the feelmg of giddiness and the aotual disorders of
equilibrium whicdi are its concomitants.

That this feeling of giddiness on rotation is due to impulses
started in the semicircular canals is shown by the fact that,
in a large number of deaf-mutes where these organs are im-
perfectly developed, it is impossible to produce giddiness and
the associated eye-movements by passive rotation.

It was mentioned above that, after destruction of the semi-
circular canals on both sides, the animal learns to guide its
movements by sensations of touch and sight alone. This
compensation depends however on the integrity of that part
of the central nervous system which is emmently teachable,
viz. the cerebral hemispheres. If these be removed in a
pigeon and later on the membranous labyrinth on each side
destroyed, the disorders of equilibrium which are produced
are permanent.

Tlie Function of the OtolitJifi

Both utricle and saccule possess special nerve-endings
known as the manihr acousticfp. These resemble the crista
acoustica of the semicircular canals in structure, being
formed by an elevation in the tunica propria of the lining
membrane, which is covered by columnar cells bearing long
stiff tapering hairs and supported by thin bipolar sustentacular
or fibre-cells. The hairs project into a mass of a soft mucus-
like substance which has a numl)er of calcareous particles
(otoliths) imbedded in it.

It is evident tliat the incidence of the weight of the
otoliths on the hairs of the macula will vary according to the
position of the head. Since similar structures have been
shown (in invertebrata) to be essential for the proper equili-
bration of the animal, it is thought that the ' otolith organ '
is specially adapted for conveying a sense of position (static
sense), while the semicircular canals are chiefly engaged in
the initiation of impulses which inform the central nervous
system of the extent and direction of rotatory movements in-
volving the head.

SPECIAL SENSES 539

Section 4
TASTE AND SMELL

By means of our sense of taste we distinguish certain
qualities of soluble substances which are introduced into the
mouth. By means of smell we determine the qualities of the
air which passes through the upper air-passages. In many
cases, as in the appreciation of flavours, both senses are
employed, and the sensations are referred to qualities of the
food or other substance in the mouth. When the sense of
smell alone is involved, the sensations are projected as a rule
outside the body, and in many lower animals must form a
considerable part of the substratum on which the representa-
tion in consciousness of the external world is built up.

Together these senses represent the chemical sense, which
is present to a greater or less degree in all living organisms,
and which can generally be divided, as in the higher animals,
into a sense regulating the intake of food, and a sense (corre-
sponding to our projected sensations) which guides the relations
of the organism to its environment. Thus the attraction of
the antherozoids of ferns by the secretion of the female organ,
the attraction of the plasmodium of myxomycetes l)y dead leaves
and its repulsion by quinine, phenomena described under
the name of positive and negative chemiotaxia, are exactly
analogous to the attraction of a dog by a bitch in heat, or to
the avoidance by ourselves of evil -smelling thoroughfares.

Taste

The end-organs of the taste-nerves are represented by
the taste-huds (Fig. 234), which are oval bodies consistmg of
medullary and cortical parts, the former being composed of
columnar cells, the latter of thin fusiform cells, among which
ramify the terminal fibres of the gustatory nerves. These occur
scattered over the tongue and soft palate, but are especially
numerous in the trenches round the circumvallate papillae. A
sapid substance to stimulate these organs must be in solution ;
hence qumine in powder is almost tasteless, owing to its slight
solubility in neutral or alkaline fluids. We distinguish four

540

PHYSIOLOGY

primitive taste-sensations, sweet, sour, l)itter, and salt, and it
is supposed that there are different nerve-fibres for each of
these tastes. The reasons for this assumption are as follows :
a. The tongue is not equally sensitive at all points to all
four tastes. Thus the back of the tongue is more sensitive
to bitter, while the tip and sides of the tongue react more to
sweet and acid tastes. Differences can be detected even
between the circumvallate papilhp themselves ; a mixture of
quinine and sugar applied to one papilla may excite chiefly
bitter taste, while with an adjacent papilla the sweet taste may
predominate.

Fio. 234.

Two taste-buils from the tongue, e, stratified epithelium ; p, opening
or pore of taste-bud ; s, gustatory cells ; st, sustentacular cells.
(Kolliker.)

h. If the leaves of Gymncma fujlvestre be chewed, the
sensations of bitter and sweet are abolished, leaving intact
the acid and salt tastes and also the general sensibility of
the mucous membrane. On the other hand, cocaine abolishes
general sensibility before it affects the sense of taste. Nor-
mally the effect of an acid is mixed with the biting sensation
due to stimulation of nerves of general sensibility. After
cocaine this pungent sensation is al)olished and acid produces
a very pure and intense acid taste.

When two taste-sensations are excited simultaneously, the
total effect depends on the strength of the exciting stimuli.
With weak stimuli, one taste may annul the other, so that

SPECIAL SENSES 541

the mixture used seems insipid. If the stimuli be then in-
creased, as by increasing the strength of the soUitions used
{e.g. acid, quinine, sugar), a compound sensation results in
which the component simple sensations are easily distinguish-
able.

Most of our so-called tastes are dependent on the sense of
smell. Without this sense there would be very little difference
between an onion and an apple. The epicure with a fine
palate has really educated his sense of smell rather than of
taste.

The nerves of taste are the glosso-pharyngeal, which
supplies the back part of the tongue, and the lingual branch
of the fifth nerve and the chorda tympani, which supply the
front part. It is doubtful however whether there are really
two nerves of taste. According to some authors the taste-
fibres of the fifth nerve are derived from the glosso-pharyngeal
nerve, perhaps reaching it through the tympanic plexus and
chorda tympani nerve. Gowers has recorded a case however
of complete unilateral loss of taste, in which there was a lesion
destroying the roots of the fifth nerve, the glosso-pharyngeal
being intact. It seems probable therefore that the fifth nerve
(as it rises from the brain) is the only nerve of taste.

Smell

The organ of smell is situated at the upper part of the
nasal cavities. Here the mucous membrane covering the
superior and middle turbinate bones and the corresponding
part of the septum is different from that covermg the rest of
the nasal passages. Over the lower parts of the nasal cavities
the mucous membrane is of the ordmary respiratory type,
and is composed of ciliated columnar epithelium containing
a number of goblet-cells. In the olfactory part however the
epithelium is much thicker, of a yellow colour, and apparently
composed of a layer of columnar cells resting on several layers
of nuclei. These nuclei belong to the olfactory cells proper,
true spindle-shaped nerve-cells with one process extending
towards the mucus covering the free surface, while the other
is continued along channels in the bone, and through the
cribriform plate as one of the non-medullated olfactory nerve-
fibres. These nerve-fibres dip into the olfactory lobes, where

542

PHYSIOLOGY

they terminate Ijy a much-branched arborisation or end-basket
in the so-called olfactory glomeruli, in close connection with
a similarly branched dendrite of the large ' mitral ' cells of the
olfactory lobe. The axons from these latter carry the olfactory
impulse towards the rest of the brain (Fig. 235). In the con-
nective tissue basis (dermis) of the mucous membrane are
a number of small mucous orserous glands (Bowman's glands)
whose office it is to keep the surface of the membrane con-
stantly moist.

A substance to excite a sense of smell must be m a gaseous
condition, although before ali'ectmg the olfactory terminations

liu. 235.

Schema of course of olfactory impulses (Ramon y Cajal^ A, olfactory
mucous memlnaiic ; B, olfactory ^^'lomeruli ; C, mitral cells; E,
granule cells ; D, olfactory tract ; L, centrifugal fibres.

it must be dissolved by the fluid bathing the nerve termina-
tions. If the nasal cavities be filled with rose water, not only
ig no smell perceived, but the sense is paralysed for some
time afterwards. This result is i)robably due to the injurious
effect of the water on the mucous membrane. It is said that
if the nostrils be filled with normal salt solution containing
odorous substances, a sensation of smell is excited, but in such
experiments it is difficult to ensure that all the chinks and
crannies of the olfactory passages are filled with the solution,
so as to exclude the possibility of the sensation being excited
in the ordinary way by diffusion into the aii- of these passages.
The sensitiveness of the olfactoi-y is much greater than
that of the gustatory organ. Thus whereas we can barely

SPECIAL SENSES 543

taste 5 parts in 10 inillioii of quinine, applied to the most
sensitive part, the l)ack of the tongue, we can perceive tlie
odour of niercaptan when it is so dikited that 1 litre of air
contains only 0*00000004 milligram of this substance.

No satisfactory classification of smells has yet been made.
The following facts however tend to show that there are
a number of primitive sensations of smell, as of other
sensations :

(a) Certain individuals, whose olfactory sense is in other
respects normal, have no power of distinguishmg some odours.
Thus one may be without the sense of smell for vanilla,
another for violets, another for hydrocyanic acid.

(6) The olfactory sense is easily fatigued. If it be fatigued
so as to be absolutely insensitive for one kijid of smell, it is
still normally excitable for other smells.

(c) It is possible by mixing odoriferous substances in certain
proportions to annul absolutely their effect on the olfactory
organ. Thus 4 grams of iodoform in 'JOO grams Peruvian
balsam is almost odourless, and the same neutralisatioi:i of
odours is obtained if the odour of each substance be allowed
to act separately on each side by tubes inserted into each
nostril .

544 PHYSIOLOGY

Section 5
HEAKING

Sound is a sensation in'oduced in our ears by vibrations
occurring in surrounding bodies, and transmitted to them by
the atmosphere.

Sounds produced by a regular series of vibrations are musical tones ; if the
vibrations are quite irregular the effect is a noise. In a musical tone we
can distinguish three qualities, according to the character of the vibrations ;
these are pitch, loudness, and timbre or quality. The pitch of a note depends
on the number of vibrations per second. A note of 400 vibrations is an
octave higher than a note of 200 vibrations. The loudness of a sound depends
on the amplitude of vibration. The timbre or quality is dependent on the
presence with the fundamental tone of certain overtones or harmonics. Thus if we
strike a piano string, the fundamental note of which is 100 vibrations, we get
superposed on this tone a series of notes whose vibration frequencies are 2, 3, 4,
5, 6, 7 hundred. It is on the varying predominance of these overtones that the
differences between the sounds of a given note produced severally by the organ,
piano, trumpet, and violin depend.

If we raise the damper of a piano and sing into it, it will be noticed that
a large number of the strings go on vibrating. This is due to the fact that
every note in our voice is accompanied by overtones, and the piano strings pick
out those overtones which correspond to them in vibration frequency (pitch) ;
they are said to resonate. Instead of piano strings we may use cylinders of
different lengths as resonators, and by employing a battery of these resonators
it is possible to analyse all manner of compound sounds.

The organ of hearing may be considered as consisting of
an accessory part and an essential part. The essential part
is formed by the terminal expansion of the auditory nerve ;
the accessory part is constructed so as to bring the waves of
sound to act on the end-organs.

The ear is divided anatomically into three parts ; the
external ear with the auditory meatus, the tympanum, and
the internal ear. The external ear in the lower animals is
fashioned so as to collect sound-waves from different direc-
tions ; and to this end it is provided with muscles, and is very
movable. This function in man is rudimentary, so that he
can hear almost as well with his ear cut off as normally.
The meatus is separated from the tympanum by the drum of
the ear, or membrana tympani. This is formed by a thin
layer of fibrous tissue, covered with skin externally, and with

SPECIAL SENSES 545

mucous membrane of the tympanum internally. Attached to
the point of its inner surface, and dragging it inwards, is the
handle of the malleus. The attachment of this to the mem-
brane is eccentric — an arrangement which is of great import-
ance, since the membrane in this way is rendered aperiodic,
i.e. it will vibrate with equal facility to any number of vibra-
tions, and not pick out a particular note, as a drum that was
equally stretched all round would do.

The cavity of the tympanum is connected in front with the
pharynx by means of the Eustachian tube. This is opened
by each movement of swallowing, so that the pressure in the
tympanum is kept equal to that of the outside air. If the
Eustachian tube be blocked by disease, the air in the
tympanum is absorbed, and the patient becomes deaf on

Fig. 23C.

Diagram of auditory meatus, with tympanum and auditory ossicles.

that side. The inner wall of the tympanum presents in
the dried skull two openings, the fenestra ovalis and the
fenestra rotunda. The former opens into the vestibule of the
internal ear and is normally closed by the base of the stapes.
The fenestra rotunda leads into the scala tympani of the
cochlea, and is closed in the fresh skull by an elastic mem-
brane. Stretching across the tympanum, from the membrana
tympani to the outer wall of the internal ear, is a chain of
ossicles, the malleus, incus, and stapes. The base of the
stapes is inserted into the fenestra ovalis, being joined to its
margins by a membrane. This chain of bones acts as a
system of levers, by which the vibrations of the tympanic
membrane are transmitted to the fluid in the internal ear.

The excursion at the end of the lever formed by the stapes
is only two-thirds of the excursion of the handle of the

35

546 PHYSIOLOGY

malleus, so that, in their transmission through the ossicles,
the vibrations are diminished in extent but increased in
force.

The tensor tympani muscle, which is attached to the
handle of the malleus, serves by its contraction to draw this
in, and to render the membrane more tense, and therefore
more easily affected by high notes. The stapedius muscle,
when it contracts, tilts the stapes backwards. Its use is
unknown.

The internal ear consists essentially of a membranous sac,
which is formed by an involution of the epithelium covering
the surface of the embryo. In the course of development the
sac, which is filled with a fluid called endolymph, becomes
much modified in shape (Fig. 237), forming from before back-

FiG. 237.

The membranous labyrinth, cm. Canalis or scala media of the cochlea.
B. Saccule, u. Utricle, s.c. Semicircular canals.

wards the scala media of the cochlea, the saccule, the utricle,
and the three semicircular canals. At certain parts of its inner
surface thickenings of the epithelium occur, which become
connected with the terminations of the auditory or eighth
nerve. This ' membranous labyrinth ' lies inside a casing
of bone, from which it is separated by a layer of fluid called
the perilymph. The osseous labyrinth is formed from before
backwards by the cochlea, vestibule, and semicircular canals.
The cochlea (Fig. 238) is a spiral tube of bone, 20 to 80 mm.
long, divided by the scala media into two parts, the scala
vestibuli and the scala tympani, which are continuous at the
apex of the spiral (helicotrema). The scala media contains
the essential part of the organ of hearing, which is called the
organ of Corti (Fig. 289). This consists of a double row of
stiff cells— the inner and outer rods of Corti, sujjporting on

SPECIAL SENSES

547

each side uiie or three rows of hair-cells, which are connected
with the terminations of the auditory nerve. The organ
rests on the basilar membrane, which is composed of a
nmiiber of elastic fibrils stretched in a radial direction from
the central axis of the cochlea to the middle of the wall of

Fir.. 238.

Vertical section tluongh the cochlea.

the spiral. The length of the fibrils forming the basilar
membrane increases from 0"041 mm. at the base to 0*495 mm.
at the helicotrema.

Somid-waves falling on the ear are collected into the
meatus, and strike the membrana tympani. The vibrations

Fk;. 239.

ni.t

Section through the end-organ of the auditory nerve in the eoclilea
(organ of Corti). b.m. Basilar membrane, c. Canal of Corti. e.g. Rods
of Corti. IH. and oh. Inner and outer hair-cells, s.c. Sustentacular
cells. An. Auditory nerve, m.t. Membrana tectoria.

of the membrane thus produced are transmitted with dimi-
nished amplitude but increased force by the chain of ossicles
to the fenestra ovalis, where they are communicated to the
perilymph. The vibrations travel in the perilymph from the
vestibule to the scala vestibuli, up the turns of the cochlea to
the helicotrema, and then back again along the scala tympani,

548 PHYSioL()(n-

a'ld end on the membrane closing in the fenestra rotunda,
situated in the inner wall of the tympanum at the base of the
scala tympani. Every movement inwards of the base of the
stapes causes therefore a bulging of the membrane closing
the fenestra rotunda. In their course the vibrations set the
basilar membrane of the scala media into vibration, and in
this way aftect the hair-cells and the terminations of the
auditory nerve.

The fact that in many cases we are able to resolve the
compound sound into its simpler components, that a musician
can name the notes forming a chord struck on the piano,
shows that there must be some mechanism in the ear by
which the sounds are analysed. This mechanism is supposed
to be furnished by the basilar membrane. It is thought
that the longer fibres near the apex of the cochlea vibrate
only to low notes, and that the shorter fibres near the base
of the cochlea vibrate only to high notes, and that when
a chord is struck it sets into vibration fibres of the basilar
membrane at different parts of the cochlea, each of which
excites the hair-cells and auditory nerve-endings lying imme-
diately on it, giving rise to a series of simple sensations.

The objection that has been raised to this theory of
Helmholtz is that there is not enough difference between the
lengths of the fibres of the basilar membranes at different
points to account for the range of sounds which it is possible
to perceive and analyse. It has therefore been suggested by
Ewald that the whole basilar membrane vibrates, but with
nodal points, so that a vibrating pattern is impressed on the
nerve-endings, the position of the nodal points, and therefore
the combination of fibres excited, differing with each tone or
combination of tones.

Another theory would avoid the difficulty altogether by
assuming that the basilar membrane vibrates as a whole like
a telephone plate, and that the impulses ascending the whole
auditory nerve differ in quality, reproducing physiologically
the varying characters of the physical disturbances by which
they were caused. Under this theory the whole process of
analysis is relegated to the central nervous system.

Difficulties in the physiological theory of audition are represented by the
so-called combination and difference tones. If two tuning-forks, one vibrating
200 and the other 250 times per second, be set vibrating, we hear not only the

SPECIAL SENSES 549

notes corresponding to these vibration frequencies but also two others, one of
50 vibi'ations per second (the difference tone) and one of 450 vibrations (the
combination tone). Since it is- said that these tones do not exist physically, we
must conclude that the sensations corresponding to them are in some way excited
in the auditory apparatus or central nervous system by the original two stimuli
of 200 and 250 vibrations per second.

The rato of vibration frequency, witliin wliieli an audible
note is produced, may extend from IG to 10,000 vibrations
per second, although in most people no sound is produced by
vibration frequencies below 30 or above 30,000. According
to Exner, two sounds following one another are perceived as
distinct if the interval between them is not less than 0*002
second.

)50 PHYSIOLOGY

Section 6
VISION

In treating of the functions of the eye, the organ of vision,
we have to consider the essential part, the termination of
the optic nerve or retina, and the accessory part, a series
of dioptric mechanisms, arranged to form a perfect image of
external objects on the retina.

Since the two eyes are generally employed together, we
have also to discuss binocular vision ; and lastly the cerebral
processes engaged in the formation of visual sensations and
judgments.

The Manner in which a Distinct Image of External
Objects is formed on the Retina

The eye may be compared to a photographic camera, the
lens ))eing represented by several refracting surfaces, the

Fig. 240.

cornea, lens, and vitreous humour, and the sensitive plate on
which the image is formed by the retina.

A ray of light when passing obliquely from a medium of
low density (such as the air) to a medium of high density
(such as water or glass) changes its course, being bent
towards the perpendicular drawn to the surface separating
the two media. On leaving the dense for a rarer medium it
is bent once more away from the perpendicular.

SPECIAL SENSES

551

Figs, 240 and 241 represent the course of a ray of light
in passing through a plate of glass with parallel sides, and
through a prism.

Fm. 241.

By means of a convex lens the rays of light from any one
source may all be refracted so as to meet at a point. The
point at which parallel rays of light (such as the sun's rays)
meet is called the principal focus of the lens (Fig. 242).

Fig. 242.

Diagram of the course of parallel rays through a biconvex lens, by
which they are converged to the principal focus, F.

If the origin of the rays be a point of light near the lens,
so that the rays are not parallel, they are converged by the
lens to a point (secondary focus) situated further away from

Fig. 243.

The rays of light from A converge on passing through the lens to
the secondary focus, F. F and A are conjugate foci.

the lens than the principal focus. The two points, the point
whence the rays of light diverge and the point to which they
converge, are caMed conjugate foci (Fig. 2481.

552

PHYSIOLOaY

111 the eye there are several surfaces separating different
media where refraction takes place (Fig. 244). Since the

Fig. 2-i4.

Section through eyeball to show refractive media. Sc. Sclerotic
coat. Ch. Choroid coat. V. Vitreous humour. L. Lens. S. Suspen-
sory ligament of lens. ON. Optic nerve. C. Cornea. A.h. Aqueous
humour. Ir. Iris.

refractive index of the aqueous humour is almost equal to
that of the cornea, we may reduce the refracting surfaces to
three, viz. —

Anterior surface of cornea.

Anterior surface of lens,

Posterior surface of lens ;
and the refracting media to three —

Aqueous humom* (or cornea),

Lens,

Vitreous humour.
These are so adapted in the normal eye that parallel rays
falling on the cornea are converged to a focus at the yellow
spot on the retina. This pomt therefore represents the
principal focus of the eye. A line drawn from this point
through the centre of the cornea is the optic axis of the
eyeball.

The Mechanism of Accommodation

But we are able also to form a distinct image of near
objects on the retina, and we notice that, when we turn our
gaze from far to near objects, there is a distinct feeling of

SPECIAL SENSES 553

muscular eftbrt in the eyes. There must tlien be some
means l)y wliich tlie eye can l)e altered and arranged for
focussing near objects. In a photographic camera the focus
may be aUered either by changing the lens, putting in one of
greater or less curvature, or by altering the distance of the
screen from the lens. The last method is obviousl}' imprac-
ticable in the rigid e3'eball, and we fnid that the act of
focussing (or accommodating) for near objects is associated
with a change in the curvature of the lens, which becomes
more convex on its anterior surface.

This may be easily shown by means of the phakoscope
(Fig. 245). This is simply a box, blackened inside, with
holes at a, b, c, and d. At (a) is the observer's eye; at (b) the
observed eye. Across the middle of (d) a wire is stretched.

Diagram of phakoscope.

A candle is placed at (c). The observer at (a) then sees
three reflections of the candle from the eye at (b) : a bright
erect image from the anterior surface of the cornea ; a
larger but dimmer erect image from the anterior surface of
the lens ; and a small very dim inverted image from the
posterior surface of the lens. These images must be observed
first when the eye at (b) is accommodated for a distant
object, and then when it is accommodated for the wire
stretched across the opening (d). It will be noticed that the
change of accommodation from far to near objects is accom-
panied by a change in the second image (that from the
anterior surface of the lens), which becomes smaller. The
change in this image is more easily seen if the candle be
made to throw two images on the eye by interposing a double
prism at (c). Then, as the lens becomes more convex to

554 PHYSIOLOGY

accommodate for near ol)jects, the two images of the candle
reflected from its anterior sm'face approach one another
(Fig. 240).

We must now inquire how this cliange in the shape of the
lens is brought about.

By measuring the size of the image of the candle produced
by the anterior surface of the lens, and knowing the size of
the candle itself and the distance from the observed eye, it
is possible to calculate the curvature of the lens in the living
body.

The radius of curvature of a reflecting surface is given approximately

2 a b

by the following formula : r=— ^ — , where r is the radius of curvature, a the

c

distance of the object, b the size of the image, and c the size of the object.

Fio. 246.

Diagram of reflected images from cornea and lens surfaces seen in
phakoscope. a. From anterior surface of cornea, b. From anterior
surface of lens. c. From posterior surface of lens. 1. During
accommodation for distance. 2. During accommodation for near
objects.

Of a, b, and c the only measurement which presents any difHculty is b, the
size of the image. For this purpose therefore the ophthalmometer was devised
by Helmholtz. The principle of this instrument may be gathered from the
diagram (Fig. 247). We may suppose that it is necessary to measure the line
a b, which may be taken to rejjresent an image reflected from the anterior
surface of the cornea or lens. If we look at this line through a plate of glass
the plane of which is at right angles to our line of sight, no distortion of the line
a b takes place. If however the plate be placed obliquely, as at gr, </,, there will
be an apparent shifting of the line sideways to c d. In the ophthalmometer
there are two glass discs, ^, (/, and g^ g.,, one immediately over the other, so placed
that the image a b is looked at through the junction between the two plates.
The plates are then turned, as in the diagram, until a b appears as two distinct
lines e c and c d just touching one another at c. At this point each image of
the line a b has been shifted through one-half the length of a b. Knowing the
thickness of the plates and their refractive index, it is easy to calculate, from
the angle through which the plates have been turned, the apparent shifting of

SPECUL SENSES

555^

the line a b. This'lateral movement amounts to a c, i.e. to , and we have

2

merely to double this result in order to obtain the actual size of the image on

the cornea or lens.

If the lens l)e now cut out of the e^ye, it is found when
freed from its supporting structures that the curvature of
its anterior surface is much greater than it was before. It is
evident that a pressure is normally exerted by some struc-
ture on the anterior surface of the lens, repressing its
natural tendencj^ to become convex. If we examine sections

Fig. 247.

Diagram to illustrate principle ol ophthalmometer (after Schenck).

through the eye we lind that this structure is the suspensory
ligament of the lens.

The membrana hj^aloidea of the vitreous is thickened in
front and closely adherent to the ciliary processes. At the
margin of the lens it divides, sending a thick tough expan-
sion forwards to cover the anterior surface of the lens, and
a thin expansion behind which separates the lens from the
vitreous humour. The part of the membrane extending
from the edge of the lens to the ciliary processes is the
suspensory ligament. This ligament is normally on the
stretch, and keeps the anterior surface of the lens nearl}'

55() PHYSIOLOGY

flat, so that the eye is accominodated for intinite distanee,
Wlieii tlie eye is to be accommodated for near objects the
ciliary processes are pulled forwards and inwards by the
contraction of the ciliary muscle, and so tlie suspensory
ligament is relaxed and the front of the lens allowed to
bulge forwards.

The ciliary muscle rmis from the corneo-sclerotic junction,
to be attached to the ciliary processes and front part of the
choroid.

Accommodation is a voluntary action, although the ciliary
muscle consists of unstriated fibres. Contraction is brought
about through the intervention of the short ciliary nerves,
which are derived from the third nerve. The nucleus of

Fig. 248.

Diagram showing change in lens during accommodation.
M. Ciliary muscle. I. Iris. L. Lens. V. Vitreous humour.
A. Aqueous humour. C. Cornea.

the third nerve is situated in the extreme hinder part of the
third ventricle and the anterior part of the iter of Sylvius.
The centre presiding over the movement of accommodation
occupies the most anterior part of this nucleus.

Movements of the Iris

Accommodation for near objects is always associated with
contraction of the iris, the function of which we must now
consider. In an ordinary spherical biconvex lens the rays
of light passing through the periphery of the lens come to a
focus at a nearer point than the rays passing through the
central parts. In this way a certain amount of blurring of
an image is produced, which is spoken of as spherical
aberration. This spherical aberration may be corrected in
three possible ways :

SPECIAL SENSES

557

1. By making the refractive index of the lens higher at
its centre than at its circumference.

2. By making the curvature of the lens less near its
circumference than at the centre.

3. By ' stopping out ' the peripheral rays of light by
means of a diaphragm.

The two latter methods are those used in most optical
instruments. In the eye there is an attempt at all three,
but the most important means is the third, the diaphragm
being formed by the iris. This is a circular curtain with a
hole in the middle, lying just on the anterior surface of the

Fig. 249.

Diagram to show couise of tlic impulses in the light rcfiex (marked
by single arrows), and of tliose which, starting from the oculomotor
nucleus, cause dilatation of the pupil (double aiuows).

lens. Pigmented cells in it effectually stop out peripheral
rays of light, and the size of the opening in it, the pupil,
is controlled by the contraction or relaxation of a ring of
unstriated muscular fibres situated near the margin of the
pupil.

The iris has a twofold nerve-supply from the third nerve
through the short ciliary nerves, and from the cervical sym-
pathetic through the Gasserian ganglion, ophthalmic branch
of the fifth, and the long ciliary nerves (Fig. 249). Stimula-
tion of the third nerve causes contraction of the pupil. The
centre for this movement is in the anterior part of the floor

558 PHYSIOLOGY

of the Sylvian iter, just behind the centre for accommodation.
Stimulation of the cervical sympathetic produces dilatation
of the pupil. The fibres serving this action leave the spinal
cord by the second dorsal nerve, and pass up through the
stellate ganglion in the cervical sympathetic. In this dila-
tation two processes are involved, viz. (1) the relaxation of
the circular muscle-fibres, the sphincter piqyilla',, and (2) the
contraction of the radiating fibres which form the dilatatur
pupilla'.

Contraction of the pupil occurs under the following con-
ditions :

1. Stimulation of the optic nerve by exposure of the
eye to light, or by artificial means. In the higher mammals
this is a crossed reflex, exposure of one eye to light causing
contraction of both pupils.

2. Associated with movements of accommodation and con-
vergence of the optic axes.

3. Various poisons, especially opium and physostigmin.
The latter drug exerts a local influence on the iris, and can
cause contraction of the pupil when all nerves to the eyeball
are cut.

4. In sleep.

The pupil is dilated —

1. When the eye is removed from light.

2. Eeflexly by strong stimulation of any sensory surface.
8. When accommodation is relaxed.

4. Under the influence of emotion, such as fear.

5. In the last stage of asphyxia.

6. In deep chloroform narcosis, and under the influence
of atropin and other alkaloids derived from the solanaceous
family. Atropin exerts a strong local influence on the iris.
Stimulation of the third nerve has no power to constrict a
pupil that is dilated fully by^atropin.

Optical Defects of the Eye

Chromatic aberration. — Since blue rays are more re-
frangible than red rays, they are brought to a focus at a
point nearer the lens than the red rays. This is the reason
why with an ordinary magnifying glass we see a coloured
fringe round the margins of the object. Chromatic aberrg,-

SPECIAL SENSES

559

tion is corrected in optical instruments by using two diHerent
kinds of glass. In the eye it is uncorrected. Hence it is
that a blue light and a red light at the same distance from
the eye appear to be unequally distant ; the red light, re-
quiring greater accommodation than the blue, appears to l)e
the nearer of the two. The error in most cases is so slight
that we do not notice the chromatic frmges under normal
circumstances.

Myopia. — The normal or emmetropic eye is so constructed
that, when the ciliary muscle is relaxed, parallel rays are

Fio. 2-50.

Diagrams of course taken by parallel rays in entering normal
(emmetropic) eye {A), hypermetropic eye (B), and myopic eye
(C).

brought to a focus on the retina. If the eyeball be longer
than usual, the parallel rays will come to a focus rather in
front of the retina, so that it will be impossible for a clear
image of distant objects to be formed on the retina. Objects at
a certain small distance from the eye will be brought to a focus
on the retina without any effort of accommodation. People
with eyes of this description are said to be myopic or short-
sighted. Under these circumstances concave spectacles are
necessary, in order to form a distinct retinal image of distant
objects.

560

PHYSIOLOGY

Hypcrmetropia. — If, on the other hand, the eyeball be
too short in its antero-posterior diameter, the parallel rays
entering the eye will come to a focus at a point behind the
retina. In order that a distinct image may be formed, even
of distant objects, it will be necessary to increase the curva-
ture of the lens by contracting the ciliary muscle. Such eyes
are hypermetropic or long-sighted.

Fig. 251.

a h e

Lens from human eye at different periods of life (Allen Thomson).
a, at birth ; b, adult ; c, old age.

Presbyopia. — As old age comes on, the lens becomes more
rigid, and loses more or less its tendency to become convex
(Fig. 251). Hence the near limit of accommodation gets
further and further with advancing age. Such a condition
is not to be confused with long-sightedness ; it is merely
a defect in the power of accommodation, and not dependent

Fig. 252.

iagrain showing course of rays in an astigmatic eye (Waller). The
curvature of the cornea is greater in the vertical meridian v v v than in
the horizontal meridian h h h. Hence the rays of light coming from the
point r and passing through the vertical meridian come to a focus at/',
while those through the horizontal meridian come to a focus at f'\
There is thus no point behind the cornea at which all the rays from P
will come to a focus, and the image of the point must be blurred, being
elongated in a horizontal direction at/', and in a vertical direction at/'''.

on a structural defect of the eyeball. It is spoken of as
presbyopia.

Astigmatism. — The curvature of the vertical meridian of
the cornea is usually greater than that of the horizontal
meridian. The difference may be so great as to make it
impossible for a definite image of a point of light to be

SPECIAL SENSES

561

formed on the retina, the rays diverging from the himinous
point in the vertical plane (greater curvature) being brought
to a focus sooner than those in a horizontal plane. To
correct this defect it is necessary to use cylindrical glasses
in order to make up for the lesser curvature of the cornea in
this direction.

Eetinal Changes involved in Vision

We have seen that, in nearly all sense-organs, the essen-
tial constituent is a bipolar nerve-cell having a peripheral
process extending towards the surface and ending between

Fig. 253.

1 -^1

6 -

_----ir' c.n.

n.M.
h

Schema of retina (from Bohm and Davidolf after Cajal).
1, nerve-fibre layer ; 2, ganglion-cell layer ; 3, inner molecular
layer ; 4, inner nuclear layer ; 5, outer molecular layer ;
6, outer nuclear layer; c, cone ; r, rod ; b, bipolar cells ; S, spon-
gioblast ; am., amacrine cell ; c.n., centrifugal nerve-fibre ;
M, fibre of Miiller ; ^i.M., nucleus of fibre of Miiller ; n, neu-
roglia ; 0, outer limiting membrane.

the epithelial cells covering that surface, and a central process
which runs towards the central nervous system, where it
terminates in close contact with other nerve-cells.

The retina however represents genetically not a simple
sense-organ, but a whole lobe of the brain, and has therefore

36

562

PHYSIOLOGY

a much more complicated structure. It is composed of three
separate relays of nerve-elements (neurons). These are —

(1) The rod and cone cells, with their nuclei (rod and
cone and outer nuclear layers).

(2) Bipolar cells (inner nuclear layer).

(3) Ganglion cells (ganglion -cell layer), from which spring
the axis-cylinders joining the nerve-libre layer, and which
run along the optic nerves and tracts to terminate in the
region of the anterior corpus quadrigeminum. The functional
connection between the processes of these three sets of nerve-

Ophthalmoscopic view of fundus of eye, showing the optic disc,
or point of entry of the optic nerve, with the retinal vessels
branching from its centre.

cells takes place in the outer and inner molecular layers
(Fig. 253).

Of these layers of the retina, the hindmost, the layer of
rods and cones, represents the end-organ of vision ; and
therefore, for distinct vision to take place, the image of
external objects must be formed on this layer. This is shown
by the following facts :

a. The point of entry of the optic nerve, where the whole
thickness of the retina is composed of nerve-fibres, is abso-
lutely insensitive to light, and constitutes the ' blind spot '
(Fig. 254),

fiPECIAL SENSES

563

h. At the macula lutea, where vision is most distinct, all
the layers of the retina are diminished except the layer of
rods and cones.

c. Piirhinjes figures. If a strong light be focussed by
means of a lens on the sclerotic just outside the cornea, and
the eye be made to stare fixedly at a dull l)ackground, an
arborescent image of the retinal vessels will appear on the
background. On moving the illumination the image of the
vessels will move in the same direction. Knowing the
dimensions of the eyeball and the distance of the background
from the eye, as well as the angle through which the light is

Fig. 255.

•Ji Xi

Dia},'ram of the path of the lays of light iu the formation of Purkinje's
figures, (v) represents a retinal vessel. When this is illuminated
from (A), a shadow is formed on the hinder layers of the retina at
(a'). This is projected along a line passing through the optic axis,
and appears to come from a point (a") on the wall. On moving the
light from (A) to (B), the image of the vessel appears to move from
(a") to (b").

moved and the apparent displacement of the image of the
vessels, the distance of the percipient part of the retina behind
the vessels may be calculated. This distance is fomid to
correspond with the distance of the rod and cone layer from
the retina] vessels, and hence this layer is taken to be the
end-organ of vision.

When light falls on the retina certain chemical and
physical changes take place. These either originate or accom-
pany the transmutation of the ether vibrations into the
nerve-impulses, which ascend the optic nerve. If a frog that
has been in the dark for some time be killed, an eve taken

564

I'JIYHIOLOGY

out bisected, and the retina removed and examined by a
weak light, it will be found that this latter has a purplish-
red colour. On microscopical examination this colour is seen
to be confined to the outer limbs of the rods. After a very
short exposure to diffuse daylight the colour disappears. The
colouring matter {rlio clop sin) may be dissolved out by means
of a solution of bile salts. The purple-red solution thus
formed also bleaches rapidly on exposure to light. By
means of this rhodopsin, photographs or ' optograms ' of
external objects may be taken on the retina. The frog's eye
which is cut out is placed in front of a window. After
some time the eye is bisected and plunged into a 4 per cent,
solution of alum, which fixes the optogram, and a permanent

Fui. 25(5.

Sections of the frog's retina. A, kept in the dark. B, after
exposure to hght, showing retraction of the cones, and pro-
trusion of the pigmented epithelium between the outer Umbs of
the rods. (Engelmann.)

inverted picture of the window with its cross-bars is obtained
on the retina.

If a retina, which has been bleached by exposure to light,
be replaced on the pigment-layer lining the choroid, in a
short time the colour will be restored. On examining sections
through the retina it is found that, in those which have
been exposed to light, the cells of the layer of pigmented
epithelium send up fine processes full of pigmented granules
between the outer linabs of the rods. In an eye which has

SPECIAL SENSES

565

been kept in the dark, on the other hand, the cells of the pig-
ment-layer are quite flat, so that the front part of the retina,
including the rods and cones, can be removed without any
difficulty (Fig. 256). Thus tiie function of the pigmented
epithelium is to supply visual purple to the outer limbs of
the rods as fast as the pigment already there is bleached by
light. It might be thought that this chemical change was
the active agent in producing excitation of the optic nerve-
fibres ; but the facts that in the fovea centralis, the region of

Fig. 257.

Three types of retinal variiition obtained on exposure to light
(Waller). I, fresh retina. 11, same retina after two hours.
Ill, same retina after twenty-four hours. The black line at the
lower border of each record marks the period of exposure to
lioht.

most distinct vision, we iind only cones which contain no visual
purple, and that in certain birds there are no rods and no
visual purple in the whole retina, show that this chemical
process, interesting though it may be, is not essential for the
conversion of light-waves into a nervous impulse.

When light falls upon the retina the cones are reti-acted,
and lie close upon the external limiting membrane ; whereas
in an eye that has been kept in the dark they extend down
between the rods as far as the pigmented layer.

506 PHYSIOLOGY

The falling of light on the retina is also accompanied by
an electrical change, which may be regarded as analogous to
the current of action in nerve.

The conditions in the retina are however rather more complicated. An
eyeball of the frog led off from its anterior and posterior surfaces shows a
current directed in the eyeball from behind forwards (the resting or demarcation
cvirrent). On allowing light to fall into the eye this current after a delay of
several seconds is markedly increased. On shutting off the light there is a
momentary further increase and then diminution of the current to its resting
value (Fig. 257, I). Waller interprets this change as showing a twofold process
of disintegration and anabolism during stimulation by light — the anabolic effect
however predominating so far as regards the changes affecting the galvanometer.
On shutting oft' light, the dissimilative changes cease at once, the assimilative
more slowly ; hence the further positive variation. On keeping the eyeball the
positive variation gradually diminishes, so that, twenty-four hours after excision,
exposure to light may cause a pure negative variation, succeeded by a slight
positive effect when the light is shut oft" (Fig. 2-57, III).

Adaptation

The sensitiveness of the retina to light is continually
altering according to the strength of the illumination. Thus,
when we go from- a brightly lighted place into a dark room,
at first we are unable to distinguish objects. The pupil
dilates widely from the absence of stimulation. In a short
time, however, ' adaptation ' occurs, and we may be able to
see quite clearly. When the eyes are removed from light to
darkness, within the first ten minutes the sensitiveness of the
retina is increased twenty-five times, and at the end of two
hours is as much as thirty-five times as great as it was in
full illumination. This adaptation is retinal and not con-
ditioned by changes in the size of the pupil, which after the
first reaction to the change of illumination resumes it's normal
size.

In the ' dark-adapted ' eye {i.e. one that has been removed
from all sources of illumination for a considerable time) a
remarkable difference is observed in its sensitiveness to light
of different colours as compared with the sensitiveness of the
normal eye. In the latter the spectrum appears brightest in
the yellow (between the lines D and E).

Tlie following figures represent the relative ])rightness of
the spectrum as it appears to the ' light-adapted ' eye : —

SPECLIL SENSES 567

Red (Fraunhofer line B) . . 32

Orange „ ,, C . . 94

Beddish yellow „ „ D . . 640

Yellow, D to E . . 1,000

Green, E. . . 480

Blue green, F . . . 170

Blue, G. . . 31

Violet, H. . . (3

In the dark-adapted eye the point of maximum brightness
is shifted towards the blue end of the spectrum, so that the
})righteBt part may lie in the green, and the red end may
become quite invisible. When the light is sufficiently reduced
in intensity, the whole spectrum may appear colourless.
Hence, in a garden full of bright flowers, at night only
.differences of black and white are perceived. As morning
dawns, the blue flowers and green leaves appear in their true
colours, while the scarlet geraniums still appear black ; while
a little later with increasing illumination all the flowers
are seen in their true colours. This colour-blindness to weak
illumination is possessed by the extreme peripheral parts of
the retina (where only rods are found) under all illuminations.
This fact, combined with the fact that the sensitiveness of the
dark-adapted eye to different parts of the spectrum agrees
with the bleaching powers of the different parts on visual
purple, suggests that we have in the retina two distinct
apparatus for the appreciation of light, viz. : —

(a) The cones, appreciating colour differences, especially
concentrated at the centre of the retina and forming the
whole fovea centralis.

(h) The rods, sensitised by the visual purple, giving
sensations only of light and darkness, and more sensitive
than the cones to weak illumination. Whereas the cones are
more easily excited by light in the yellow part of the spectrum,
the rods are more excited l)y the more refrangible rays of the
green and blue.

t)

Binocular Vision

Under normal circumstances we use both eyes in seeing.
Since however the visual impression produced by the two
retinal images is not double but single, there must be a series
of points in each retina which, stimulated simultaneously,

568

PHYSIOLOGY

give rise to a single impression. These points are called
' corresponding ' points. Thus, when we look at a spot, the

Fig. 258.

dbt.sup.

oil. Slip.

Sl/Jl,

r.i'nt

r.ext. r.suj). r.int
r.iftf.

Diagram to show points of attachment and lines of action of
extrinsic ocular muscles.

axes of the eyes are so directed that an image of it falls on
the yellow spots of the two retinae. The images of all points
to the right of this spot will fall on the nasal side of the

40

Fio.

2.59.

T.Bup.

/so

/lO
30

3o\

20

10

30 20 10 1

10 20 30
10

30 /

20

50X
ol9LBnp

Uo
Wo

\50
r.inf

T int

40

Diiigram to show direction in which pupil will move under the
action of the various ocular muscles.

SPECIAL SENSES 569

right retina and on the temporal side of the left retina, and
vice verm. So if the riglit retina were cut out and placed on
the left, the corresponding points in the two retina? would be
exactly over one another. In order that we may have single
vision it is necessary that the images of external objects
should fall on corresponding points of the two retinae. This
is effected by the harmonious co-operation of the muscles of
the eyeball. These are six in number : superior, inferior,
external, and internal recti, superior and inferior oblique.
The action of these muscles is as follows :

Superior rectus moves the centre of the cornea upwards and inwards
Inferior „ „ „ downwards and inwards.

Internal „
External „
Superior oblique
Inferior „

directly inwards,
directly outwards,
downwards and outwards,
upwards and outwards.

So the muscles required for the following movements
will be —

Looking upwards, superior recti and inferior oblique muscles.
„ downwards, inferior recti and superior oblique muscles.
,, inwards (convergence of eyes), the two internal recti.
„ to the right, the right external rectus and the left internal rectus.
,, to the left, the left external rectus and the right internal rectus.

The movements of the e^^es to one side or the other are
spoken of as conjugate deviation. The centres of most of
these movements are situated in the floor of the iter of
Sylvius. The movements which involve the external recti
are carried out by the nucleus of the sixth nerve, which is
functionally connected with nuclei in the floor of the iter by
the posterior longitudinal bimdle.

If from weakness of one of the ocular muscles the optic
axes cannot be made to converge to any pomt in the field of
vision, so that the images of external objects do not fall upon
correspondmg pomts of the two retinae, double vision results,
and the patient is said to suffer from a squint. In this case
the image which is formed in the sound eye is spoken of as
the true, and the other the false image. From the relation
in space of the false to the true image, it is possible to tell
which muscle is affected.

570 PHYSIOLOGY

Visual Sensations

When a ray of light from an object to the outer side of
the eye falls upon the cornea, an image of it is formed on the
nasal side of the retina. If the source of light be above the
visual axis, the image is formed on the lower half of the
retina. Hence, whenever the retina is excited at these points,
whether by light falling on the eye from without or by direct
stimulation, we refer the sensation produced to some position
in the outside world which the experience gained by all our
other senses points out.

Thus if the right eye be turned inwards, and pressure with
the finger made on the outside of the sclerotic near the outer
angle of the eyelids, we have a sensation of a ruig of light
produced by the direct excitation of the outer part of the
retina, which we refer or ' project ' to a point on the extreme
inner side of the eye. It has often been discussed how it is
that we see external objects erect when the retinal image is
inverted. But we do not look at the image on the retina.
The stimulation of the retina at a point on the nasal side
merely gives rise to sensations which experience has taught
us to recognise as coming from an object to the outer side of
the visual axis.

Atrophy of the nasal half of the right retina therefore
would give rise to blindness to the outer side of that eye,
which would probably be recognised only when the left eye
was closed.

lufen.'iLty of stimulus. — Weber's law, that the increase of
stimulus necessary to cause an increase of sensation always
bears the same ratio to the whole stimulus, holds good also
for visual sensations.

This ratio in the case of the eye is about j-jVtt- We can
thus distinguish between two lights of 20 and 20^^ candle-
power, or between two of 99 and 100 candle-power. If the
illumination be excessive the law no longer holds good ; and
we should be unable to tell the difference between two arc
lamps at a short distance, although one might be much
stronger than the other, and the difference much greater
than y-i-jy of the total light.

Duration of stimulus. -We do not knov how long a

SPECIAL SEiSrSES 571

stimulus of light must act on the retina in order to produce
a definite sensation. But the duration is very short, since
an electric spark, which is almost instantaneous in its ap-
pearance and disappearance, may excite a strong sensation
of light. This momentary stimulus however, as in the case
of muscle, excites a condition of activity and change in the
retina which lasts a measurable period.

The sensation produced by a momentary stimulus rises
sharply to a maximum and then sinks, first quickly and then
more gradually. The first part of the fall, after the attain-
ment of the maximum sensation, is more rapid in the case of
strong than of weak stimuli.

This duration of the sensation after the stimulus has
ceased may be so pronounced, when the stimulus is very
strong, as to give rise to a definite ' after-image.' After
looking at the sun for some time and then turning away,
we may see an after-image that may last several seconds or
minutes.

If one stimulus follows another at a very short interval
we get a summation of stimuli, and the two sensations are
fused into one. The interval which must intervene between
two stimuli, in order that two distinct sensations may be
produced, is greater when the stimuli are small than when
they are intense.

This interval may be determined by causing a disc, on
which alternate sectors of black and white are painted, to
revolve at known rates, and noticing the time that a white
sector takes to pass a given point (in the visual axis) when
the sensations are just fused. If the illumination of the disc
be feeble, this time will be found to be about jV second.
If now the illumination be increased, the grey disappears,
and we observe a flickering of the disc due to imperfect
fusion of the separate visual sensations (cf. imperfect tetanus
of muscle). In the latter case the time between two suc-
cessive stimuli may be reduced to ^ or -V second before
apparent fusion of the sectors takes place.

The production of a circle of light when a stick with a
glowing end is rapidly whirled round, and all the effects of
pyrotechny, are dependent on this persistence of retinal
activity after the stimulus calling it forth has ceased.

572 PHYSIOLOGY

Colour Vision

If a ray of white light be passed through a prism, it is
unequally refracted, so that it is widened out into a broad
band or spectrum, which is variously coloured, the red rays
at one end being less refrangible than the blue rays at the
other. We may divide the colours of the spectrum into
seven — red, orange, yellow, green, blue, indigo, violet; but
the division is quite arbitrary, the colours shading so gradu-
ally into one another that no two observers would agree
exactly on the limits between them. This spectrum can be
recomposed by another prism in the reverse direction with
the formation of white light, so that we say white light is
composed of all these different colours. It might at first be
thought that the retina could respond with a simple sensa-
tion to stimulation by any part of the spectrum, a low number
of ether vibrations per second producing a sensation of red,
a number rather higher a sensation of orange ; so that the
sensation produced by any part of the spectrum would be a
simple colour sensation, of which there would in this case
be an infinite number. But a simple analysis of our own
sensations seems to show that some of the spectral colours
are mixed sensations. Thus most people will say at once
that orange is a mixture of red and yellow, and as a
matter of fact we find that, on mixing rays from the red with
others from the yellow part of the spectrum, we do get a
sensation of orange. The stimulus obtained by mixing red
and yellow rays is not the same as a stimulus caused by rays
from the orange part of the spectrum. In the former case
compound waves made up of the two wave-lengths, 656 X and
564 X, are falling on the retina ; in the latter case a simple
wave with length 608 A, ; and yet the sensations produced are
identical.

In order to recompose the white light it is not necessary
to mix all the spectral colours. We may take a pair of
colours, situated a certain distance apart in the spectrum,
and by combining these form white light. Thus red with
green, or blue with j^ellow, will give white light. Any pair
of colours, which together give rise to a sensation of white, are
called comphmentayy. By taking three colours, such as red,

SPECIAL SENSES 573

green, and violet, it is possible by mixing them in various
proportions to form either white light or any colour of the
spectrum. The colours so formed differ from the spectral
colours in being less saturated; i.e. the}^ contain, besides the
pure colour, white light.

These experiments on mixing colours can be performed in various ways.

A. Sectors of the different colours are painted on a disc, and the colour
sensations are fused by rapid rotation of the disc (Maxwell's colour-top).

B. Two small coloured discs are placed on the table, with a vertical glass
plate between them. It is possible so to arrange the direction of vision that
the reflected image of the disc from the glass plate coincides in position with
the other disc seen through the plate.

c. These methods with painted discs are open to the objection that no
pigments give perfectly pure colour sensations. It is therefore better to use the
pure colours of the spectrum itself, combining any two portions of the spectrum
by means of reflectors or prisms. A less perfect method is to cause light from
two sources, coloured by different coloured glass, to fall on the same surface.

These facts show that in all probability the primitive
colour sensations are few in number, and that the various
colour sensations of a spectrum are not pure, but mixtures of
these primary sensations. There are two theories of colour
vision^the Young-Helmholtz and Hering's.

According to the former, there are three primary' colour
sensations — red, green, and violet — each of which is repre-
sented by a separate set of nerve-fibrils. One set of fibres
is most sensitive to red rays, and only slightly sensitive to
the green and blue parts of the spectrum ; the second set is
most sensitive to the middle, and the third set to the blue
end of the spectrum. White light is produced by an equal
stimulation of the three sets.

Hermg distmguishes four primary colour sensations — red,
yellow, green, and blue — and also considers the sensations
of white and black as primary visual sensations. These
sensations are placed m three groups, red and green, yellow
and blue, white and black. For each pair of sensations he
considers that there is a special substance in the retina, dis-
similation or katabolism of which gives rise to one colour
sensation ; anabolism or assimilation to the other. Thus if
white light falls on the retina, it causes a breaking down or
katabolism of the white-black substance. This breakmg
down excites certain fibres of the optic nerve, and produces
m consciousness a sensation of white. If the light be now

571

PHYSIOLOGY

removed, this bretiking down gives place to anabolism or
building up of the white-black substance, which excites the
same nerve-fibrils in a different way, giving rise to a sensa-
tion of black. The white-black substance is affected not
only by white light, l)ut also by the colours red, green,
yellow, blue, and their mixtures. The other two visual sul)-
stances are affected only by red and green or by yellow and
blue respectively. Hence even the spectral colours do not
give rise to pure sensations, there being always some mixture
of a sensation of white with the proper colour sensation.

The phenomena of colour vision that we have mentioned
above can be equally well explained on either theory. Thus
the fact that blue and yellow together give rise to a sensa-

Fk;. 260.

''"'"''"!||ii!'i''"ii'ifcii«^

-^ jiailiilil

_J^. iiijmnTininntl]

liiJiaiMiiPiiMM^^

o

ni.

Curves showing sensitiveness of the three varieties of nerve-
fibres to different parts of the spectrum. 1. Red fibres.
2. Green fibres. 3. Violet fibres.

tion of white may be explained on the Young-Helmholtz
theory by saying that the stimulation of all three sets of
fibrils is equal — as will be seen by adding together the
ordinates of each curve in Fig. 260 at yellow and at blue.

Adopting Bering's hypothesis, we may say that, anabolism
and katabolism being equally excited in the yellow-blue
substance, no change in it takes place, and the sole sensa-
tion is that produced by the stimulation of the white black
substance.

The fact that any coloured light, if very dim or if falling
on only a minute part of the retina, produces a sensation of
white, is more readily explicable on Bering's than on the
Young-ITelmholtz tlieory.

Cases a]'e not rare in which a person is unable to dis-

SPECIAL SENSES 575

tiiiguisli between reel and green, so that he can only tell a
cherry from the leaves on the tree by its shape. Such cases
may be explamed on either theory. Bering's theory how-
ever seems necessary to account for the cases of complete
colour-blindness which are said to occur. In these the only
sensations are of light and shade, and we may suppose that
the red-green and blue-yellow substances are lacking in the
retina.

Contrast phenomena. — If a grey disc be placed on a piece
of red paper, and the whole covered with tissue-paper, the
disc will take on a greenish tinge. If the ground colour be
green, the disc will appear red ; if blue, the disc will appear
yellow ; in fine, whatever be the ground colour, the colour
of the disc will be complementary to it. These effects are
spoken of as simultaneous contrast.

If, after gazing steadily for some time at a red disc on a
white surface, the eyes be turned towards a plain white
surface, a negative after-image of the disc is seen on the
paper, coloured green, i.e. the complementary colour of
the red disc. Surrounding this the paper appears red. If
we look at the sun for some time, and then turn our eyes
away, there is at first a positive after-image, and we see a
bright sun wherever we look. In a short time this dis-
appears and gives way to a black sun (a negative after-
image). Thus we may say that stimulation of any part of
the retma with any colour is followed by a colour sensation,
referred to the same part of the visual field and comple-
mentary to the first.

It has been much discussed whether these phenomena are
simply effects of judgment, or whether they are produced
by definite changes taking place m the retina.

Helmholtz explains them by the first hypothesis, and looks
upon them as cerebral processes.

Hering, on the other hand, has extended his theory so as
to embrace these phenomena, and ascribes them to definite
changes in the retina, or at any rate in the peripheral part
of the visual mechanism.

A corollary to his theory that we mentioned above is that,
if dissimilation of a visual substance be excited at any point
of the retina, assimilation of the same substance is set up in
the parts of the retina immediately adjoining that point. In

576

PHYSIOLOGY

this way the phenomena of simultaneous contrast may be
explained.

Thus if a ray of red light falls on any spot, it may be
supposed to excite dissimilation of the red-green substance
at this spot. This sets up assimilation of the same substance
in the adjoinmg parts of the retina, and the red object is
therefore surrounded with a green halo, which at once
becomes evident if we increase our appreciation for slight
colour-tones by diminishing the total amount of light by
means of tissue-paper.

The question between the two theories is whether the contrast phenomena
depend upon psychical or retinal events. There' is no doubt that the question
must be answered in the latter sense, and that these phenomena are quite
independent of the judgment of the individual. This is shown clearly by two

Fig. 2(51.

Purple

Purple Yellow

Green Purple

Purple

experiments. A box (Fig. 2(51) is divided into two long compartments, a b and
c d. At a the compartment is closed by a red glass-plate and at c by a blue
glass-plate. Apertures are provided at b and d for the observer's eyes. At
-f and + two small grey crosses are fixed about the middle of the compartment
on sheets of transparent glass. On looking through the openings b and d and
converging the eyeballs so as to fix e line o, we get a fusion more or less
complete of the two colours, red blue, so that the background appears

purple ; or there may be a struggle between the colours, at one time blue, at
another red predominating. To the judgment however there is one background
and not two, and therefore, according to the theory of Helmholtz, the grey
crosses should by contrast both acquire the same induced colour, which would
be complementary for purple. But it is found that the two crosses are perfectly
distinct in colour, that which is seen by the eye against the blue ground

SPECIAL SENSES 577

yellow while that on the red ground is green, showing that the phenomena of
simultaneous contrast are peripheral and not cerebral in their causation. The
same fact is very definitely established by the following experiment devised by
Sherrington. The disc (Fig. 262) presents two rings, each half blue and half
black. The outer ring is intensified when at rest by simultaneous contrast, the
black half being seen against the surrounding yellow, while the luminosity of
the blue half is increased by the effect of the surrounding black. In the inner

Fig 262.

ring the blue half is darkened by contrast with the surrounding yellow while
the black half is not evident at all. If the disc be rotated, we get two concentric
rings on an apparently homogeneous field. It is found however that the outer
ring flickers long after complete fusion has taken place in the inner ring,
showing that the stimulation of the retina by the outer ring is increased under
the influence of contrast.

On this theory successive contrast phenomena are analo-
gous to certain phenomena we have already studied in other
tissues. If extensive breaking down of the visual stuff has
been occurring, when the stimulus is removed there will be
a swing back of the condition of the protoplasm of the nerve-
endings in the opposite direction, and the katabolic will be
replaced by anabohc changes ; just as, on breakmg a con-
stant current that has been flowing through a nerve, the
condition of raised irritability at the kathode gives place to
a condition in which the irritability is depressed below the

normal.

The improving effect on the heart of stimulation of the

37

578

PHYSIOLOGY

vagus is also exactly analogous to a successive contrast
effect. During stimulation of the vagus the breaking down
of the contractile substance is stopped or checked, so that
building up or anabolism can go on without interruption.
When the excitation of the vagus ceases there is an extra
store of contractile material in the muscle-cells. This causes
the beat to be more vigorous, and we may say that the
increased anabolism has been followed by a period of in-
creased katabolism, just as strong stimulation of a part of
the retina with green (anabolism) gives rise to a red after-
image (katabolism).

Visual Judgments

Size. — The apparent size of an object is determined by
the magnitude of its image formed on the retina. As will
be evident from the diagram (Fig. 263), the apparent size in
any diameter of any given object is inversely proportional to
the distance. Thus the size of the image on the retina of an
object two inches long at a distance of one foot is equal to the
image of an object four inches long at a distance of two feet.

Fig. 263.

An object can be seen if the visual angle subtended by
it (the angle A c B in Fig. 263) is not less than sixty
seconds. This is equivalent to an image on the fovea cen-
tralis of the retina about 4 /x ^ across, which corresponds to the
diameter of a cone.

Estimation of distance depends partly on muscular sensa-
tions from the degree of accommodation and of convergence
of the optic axes, partly on comparisons of the apparent
size of the object with that of a neighbouring object (such
as a man) the real size of which is known, and partly on

fx = 0-001 millimetre.

SPECIAL SENSES

579

the amount of blurring of the outlines of the object due to
the haziness of the atmosphere. The latter factor is of
great importance when the object is too large and remote to
be compared with others of a known size. After a storm of
rain distant mountains may seem to be many miles nearer
than they did before.

Judgment of Solidity — Stereoscopic Vision

If we look at a solid object, such as a cube, with both
eyes, the images formed on the corresponding points of the

Fig. 2G4.

two retinse are not identical, the one in the right eye repre-
senting more of the right side of the cube, and in the left eye
more of the left side (Fig. 264).

If the two images (a) and (b) be so arranged that they fall
on corresponding points of the two retinae, the resulting
impression is that of a solid body, in the form of a cube.
This is the principle involved in the stereoscope. When
only one eye is used, the external world has a much flatter
appearance, although some idea of solidity is still gained
from the fact that the accommodation has to be altered in
order to bring different parts of the solid body into focus.
The effects of light and shade also aid in the judgment of
solidity.

Accessory Parts of the Eye

The eyeball is protected in front by the eyelids. These
are lined internally with a delicate mucous membrane, con-
tinuous with the conjunctiva covering the anterior surface of
the eyeball. This membrane is kept constantly moist by
the secretion of the lachrymal gland, a small acino-tubular
gland built up on the type of a serous gland, situated at the
upper and outer angle of the orbit. The excess of fluid is

580 PHYSIOLOGY

drained off by the nasal duct, which leads from the conjunc-
tival sac to the nasal cavity on the same side. If the eyes
be kept open for some minutes, the conjunctiva covering the
eyeball becomes dry, and irritation is set up. Normally the
membrane, and especially that over the cornea, is kept moist
and transparent by involuntary movements of the eyelids,
which close or blink about twice a minute, and so distribute
the lachrymal secretion over the whole conjunctival surface.

This blinking is a reflex act, the afferent channels being
fibres of the fifth nerve, and the efferent the fibres of the
facial nerve supplying the orbicularis palpebrarum. It is
spoken of as the ' conjunctival reflex,' and is one of the last
reflexes to disappear in chloroform or ether narcosis.

The Nutrition of the Eyeball. The Intraocular Pressure

The eyeball is formed of a tough inextensible capsule, the
sclerotic, filled with fluid or semi-fluid contents. In order that
the eyeball may be sufficiently rigid to maintain the normal
relations of the various refractive media, and to afford a fixed
point for the action of the ciliary muscle, this fluid must be
under pressure. On connecting a small manometer with the
anterior chamber, care being taken to prevent any escape of
the intraocular fluid, it is found in the normal eye that this
pressure is about 25 mm. Hg. On making an opening into
the cornea the fluid drains away, and the eyeball becomes soft
and collapsed, the cornea becoming folded, and the eye being
naturally useless as an optical instrument. The fluid which
flows away, and which forms the aqueous humour and also
fills the interstices of the gelatinous tissue of the vitreous,
contains only a minute trace of proteid, consisting in every 100
parts of 98-7 parts water and 1-2 to 1*3 total solids, of which
only 0-08 to 0*12 parts consist of proteid. If a cannula be kept
in the anterior chamber this fluid rapidly alters in character,
becoming coagulable, and containing 3 to 4 per cent of proteids.

The intraocular fluid is continually being renewed. The
eyeball receives a rich vascular supply, which forms a close
network of vessels and capillaries in the choroid coat, with its
prolongations the ciliary processes and iris. The chief seat
of formation of the intraocular fluid is the ciliary^processes.

SPECIAL SENSES. 581

Here there is a constant transudation of fluid from the blood-
vessels into the anterior part of the vitreous cavity, the amount
of the transudation varying with the pressure in the blood
capillaries, being increased by any rise in the capillary blood
pressure or by any fall in the intraocular pressure. Of the fluid
poured out by the ciliary processes a very small proportion
(perhaps one-fiftieth) passes backwards into the vitreous humour
and gradually drains out of the eyeball by the lymphatic spaces
of the optic nerve. By far the larger amount passes forward
through the fibres of the suspensory ligament into the posterior
chamber (the annular cavity between the iris in front and
the lens and ciliary processes behind), and thence round the
margin of the iris into the anterior chamber. From the anterior
, chamber it passes into the spaces of Fontana at the outer angle
of the chamber, whence, under pressure, it can filter slowly
between the endothelial cells lining the canal of Schlemm into
this vessel and so into the venous system.

A considerable resistance is offered to the passage of fluid
into the canal of Schlemm. Hence the constant transudation
of fluid from the ciliary processes raises the intraocular pressure
to 25 mm. Hg., and a continuous production of about 6 cubic
millimetres of fluid per minute suffices to maintain the pres-
sure at this height. If the anterior angle of the eye becomes
blocked, the absorption of intraocular fluid becomes more
and more difficult. There is therefore a rise of intraocular
pressure to far above normal, and in consequence there is
atrophy of the retina followed by disturbance of the nutrition
of the whole eyeball. This condition of raised intraocular
tension occurs in the disease known as glaucoma.

The constant renewal of the intraocular fluid is important,
not only for the maintenance of the intraocular pressure, but
also for the nutrition of the structures such as the lens, sus-
pensory ligament and vitreous humour, which do not receive
any vascular supply.

582

CHAPTER XIV

THE SPINAL CORD

Section 1
STKUCTUEE AND TKACTS OF THE COED

The spinal cord and bulb may be regarded in two lights,
as a centre presiding over reflex actions and as a channel of
communication between the periphery and the brain. Its
structure corresponds, roughly speaking, to this twofold
action, consisting as it does of a tube of grey matter
internally, which may be looked upon as a collection of
reflex centres, surrounded externally by a layer of white
matter, composed of medullated nerve-fibres and serving as
simple conducting tissue. It lies in the spinal canal, pro-
tected by its three membranes, dura mater, arachnoid, and
pia mater, and suspended by the attachment of its thirty-one
pairs of nerves, as they pierce the dura mater. The structure
of the cord is best studied in cross-sections. A cross-section
through the dorsal region is approximately circular, and
consists of two symmetrical halves, separated in front by the
anterior fissure, and behind by the posterior fissure. Each
half contains a crescentic or comma-shaped area of grey
matter, surrounded on its front, lateral, and mesial borders
by white matter, and connected by an isthmus to the crescent
of the opposite half. In the centre of this isthmus is the
central canal of the cord, the grey matter ui front and behind
it being known as the anterior and posterior grey commissures.
At the base of the anterior fissure the white matter is con-
tinuous between the two halves of the cord, forming the
anterior white commissure.

The Nerve-roots

Each nerve of the thirty-one pairs that arise from the
spinal cord has two roots, anterior and posterior. The

THE SPINAL CORD

683

anterior root arises by several bundles from the antero-
lateral part of the cord ; the posterior root arises as a smgle
bundle, emerging from the spinal cord opposite the posterior
horn of grey matter. The two roots join to form the trunk
of the spinal nerve. On the posterior root, just before it
joins the anterior root, is situated a ganglion, the posterior
root ganglion.

If we study the development of these roots, we find that
they have different origins. Whereas the axis-cylinders of
the anterior roots are formed by the outgrowth of the axons
of cells in the grey matter of the cord, chiefly in the anterior
cornu (Fig. '265), the posterior roots are derived from a

Fig. 265.

Transverse section of spinal cord of chick to show developing
nerve-roots (stained by Golgi's method) (Ramon y Cajal). A,
anterior root-fibres growing from the anterior cornual cells, c ;
B, posterior root-tibres passing from bipolar cells of ganglion
into cord.

separate mass of cells formed from the epiblast close to the
dorsal surface of the cord. These epiblastic cells become
oval and send out a process at each extremity, one process
growing into the spinal cord, while the other meets the
anterior roots and grows with these downwards towards the
periphery. In some animals, such as fishes, the cells of the
posterior root-ganglia retain this bipolar character through-
out life, and this is also the case with the analogous ganglion
situated on the course of the auditory nerve in the cochlea,
the so-called spiral ganglion. In all higher vertebrates
the two processes of the cells of the spinal ganglia
become approximated in the course of growth and finally

584 PHYSIOLOGY

arise from the cell as one process which divides into two by
a T-shaped junction at the first node of Eanvier.

Thus from the point of view of development, the nerve-
fibres making up a mixed spmal nerve are of twofold
origin, and represent the arms or elongated processes of
two distinct sets of cells. If a unicellular animal be cut
into two parts, it is found that the half containmg the nucleus
will regenerate the missing part and will continue to live,
whereas the part which contains no nucleus, although able
for a short time to carry out movements or even to ingest
food-granules, is unable to assimilate its food and grow, and
finally dies. Exactly the same thing happens in the case of
a nerve-cell. If we cut through that part of the cell which
forms the axis-cylinder of a nerve-fibre, the part cut av^ay,
although for a time excitable and able to conduct impulses,
finally dies ; whereas the part attached to the cell-body with
its nucleus continues to live and may under favourable
circumstances regenerate the part that has been cut off.
These facts furnish the basis of a method for determining
the exact situation of the nerve-cell from which a given axis-
cylinder is derived.

We have already seen that section of a peripheral nerve
causes, after a small initial rise, a gradual fall of irritability
in the part of the nerve below the section. This goes on to
complete loss of irritability, and on microscopic investigation
it is found that the physiological change is accompanied by
definite progressive structural changes.

About four days after the section (in mammals) the myelin
forming the medullary sheath of the nerve-fibres in the
peripheral part of the nerve becomes segmented, and breaks
up into drops of various size (Fig. 266). A little later the axis-
cylinder is also broken across, so that there is no longer any
physiological continuity in the nerve-fibre. This is followed
by enlargement and proliferation of the internodal nuclei ;
the protoplasm within the primitive sheath increases in
quantity, and the drops of myelin are gradually absorbed
and disappear. Finally, about the twenty-first day or later,
the original structure of the nerve-fibres has entirely dis-
appeared, and they consist merely of a tubular sheath, contam-
ing nuclei and structureless protoplasm. If no regeneration
can take place these structures also disappear, giving place to

THE SPINAL CORD

585

simple connective tissue. If however, after the section, the
two ends of the nerve have been kept in close apposition by
means of sutures, regeneration of the peripheral part of the

Fig. 266.

// \/-

Degeneration and regeneration of nerve-fibres in the rabbit
(SchJifer, after Eanvier). A, part of a nerve-fibre in which
degeneration has commenced in consequence of the section,
fifty hours previously, of the trunk of the nerve higher up ;
viy, medullary sheath becoming broken up into drops of
myelin ; p, granular protoplasmic substance which is re-
placing the myelin ; n, nucleus ; g, neurilemma. B, another
fibre in which degeneration is proceeding, the nerve having
been cut four days previously ; p, as before ; cij, axis-cylinder
partly broken up, and the pieces inclosed in portions of myelin.
C, more advanced stage of degeneration, the medullary sheath
having almost disappeared, and being replaced by protoplasm
in which, besides drops of myelin, are numerous nuclei which
have resulted from the division of the single nucleus of the
internode. D, commencing regeneration of a nerve-fibre.
Several small fibres, t' t", have sprouted from the somewhat
bulbous cut end, b, of the original fibre, t; a, an axis-cylinder
■which has not yet acquired its medullary sheath ; s, s', primi-
tive sheath of the original fibre. A, C, and D are from osmic
preparations; B from an alcohol and carmine preparation.

580 PHYSIOLOGY

nerve takes place. New axis -cylinders grow out from the
old axis-cjdinders of the central part of the nerve at the
node of Ranvier just above the point of division, and these
grow down into the structureless protoplasm filling the
sheaths of the peripheral nerve-fibres, thus restoring func-
tional continuity. The myelin sheaths of the regenerated
nerve-fibres make their appearance rather later. Nerve-
fibres have already been spoken of as being enormously
elongated cell-processes, and it seems that a fibre degenerates
whenever it is separated from the cell of which it is an out-
growth, and must be regenerated by a renewed outgrowth
from this cell. We may look upon the nerve-cells as
presiding over the nutrition of the fibres which spring from
them ; and they are therefore called the * trophic centres ' of
these fibres. If a nerve be divided, only that half which is
separated from its trophic centre will degenerate. This fact
was first pointed out clearly by Waller, and hence the method
of diagnosing the course of tracts in the central nervous
system is named the Wallerian method.

A large majority of the white fibres of the spinal cord are
dependent for their nutrition upon their continuity with a
nerve-cell, and if this be abolished the part of the nerve-fibre
severed from the cell degenerates. If the anterior root be
divided, the part attached to the cord remains intact, but the
whole peripheral part of the fibres degenerates, so that in a
section of the mixed nerve the degenerated motor-fibres can
be identified (Fig. 267, II).

If the posterior root be divided between the ganglion and
its junction with the anterior root, all the sensory fibres in
the mixed nerve below the junction degenerate. If however
it be divided between the ganglion and the cord, the sensory
fibres in the mixed nerve remain intact, but the central parts
of the fibres degenerate right up into the cord, and may be
traced in the cord as far up as the medulla.

It has already been stated that the anterior root is motor
or eft'erent, and the posterior root sensory or aft'erent. The
evidence for this is as follows : — If the anterior root be
divided, the muscles supplied by the nerve are paralysed.
Excitation of the peripheral end of the anterior root will
cause them to contract. Excitation of its central end has
no effect.

THE SPINAL COED

587

Section of the posterior root causes loss of sensation in
its area of distribution. Stimulation of its peripheral end
has no effect. Stimulation of its central end causes marked
signs of pain, such as struggling, crying out or, in a curarised
animal, rise of blood-pressure.

In some cases we may find that stimulation of the peri-
pheral end of the anterior root gives rise to evidence of
pain. This is spoken of as recurrent senslhility^ and is due
to stimulation of fibres which leave the cord by the posterior

Figures (from Yeo) to illustrate the degree and direction of
degeneration as a result of section of the spinal roots.
I, division of whole nerve below ganglion. II, division of
anterior root. Ill, division of posterior root above ganglion.
IV, division of posterior root above and below ganglion.

roots, and after travelling some distance towards the peri-
phery turn back and run up in the anterior root. Recurrent
sensibility is abolished, as would be expected, by division of
the posterior root.

The Grey Matter of the Cord

The crescentic mass of grey matter in each half of a cross-
section of a cord is larger in front than behind, the anterior
and posterior halves being spoken of as the anterior and
posterior horns or cornua respectively (Fig. 272, p. 593).
Each horn is again divided into the caput or head, forming the
large extremity, and the neck, which is the narrower part by
which the caput is connected with the central mass of grey
matter. When examined in section, the grey matter at first
presents an inextricable confusion of nerve cells and fibres of
all descriptions. But of late years various methods have come
to our assistance in the unravelling of the tangled mass. The

588 PHYSIOLOGY

most important of these methods are the methylene blue
method of Ehrlich and Golgi's silver chromate method with
its various modifications. Both these methods stain nerve-
cells with all their processes, and since in a given segment
of the cord only a few of the nerve-cells are stained, it is
possible to trace their processes through a considerable
thickness of the cord. The grey matter consists of nerve-
cells with their processes, of the branching terminations of
various nerve-fibres derived from the white matter of the cord
or the posterior nerve-roots, and of the supporting framework

Fig. 268.

Nerve-celJ from the spinal cord, stained by Nisd's naethod.
a, axis-cylinder process or axon ; fe, protoplasm of cell, con-
sisting of c, fibrillated gromid substance, and e, the granules
of Nissl ; d, nucleus. (Lenhossek.)

or neurogha. All the nerve-cells of the cord are multipolar
(Fig. 268). The processes however are of two kinds. One
kind of process, the neuraxon or axon, of which only one
is present, is in most cases prolonged into a nerve-fibre, of
which it becomes the axis-cylinder, generally acquiring at
the same time a medullary sheath. This process may send
off a few fine branches, the so-called collaterals, but in most
cases does not undergo any extensive branching until
nearing its periphery, where it may break up into the rich
arborisations with which we are already acquainted as the

THE SPINAL COED

589

motor and sensory nerve-endings. All the other processes
of the cell are generally thicker at their origin than the
axon, and very rapidly break up into branches which end
freely in the neighbouring grey matter. In many cases
these dendrites have serrated margins— an appearance espe-
cially well-marked in certain cells of the cerebrum and
cerebellum. The body of the cell, sometimes called the peri-
karyon, is granular and surrounds a large vesicular nucleus
with well-marked nuclear membrane, which only stains
faintly with nuclear dyes. By special methods a fibrillation

Fig. 269.

The point of origin of the axon, the ' nerve-hillock,' highly
magnified, to show absence of Nissl's granules from the origin
of the process. (Held. )

of the protoplasm has been demonstrated, the fibrillae sweep-
ing across the cell from process to process, and many converg-
ing towards the point of origin of the axon (Fig. 269). While
some observers regard this fibrillation as an artefact due to
the coagulating reagents employed, others attach extreme
importance to it, and look upon the fibrillae as the essential
conducting elements of the central nervous system, continuous
from cell to cell and throughout the whole body.

According to most observers however, such an anatomical
continuity does not exist, at any rate in vertebrate animals.
All the constituents of the central nervous system arise from
cell-units, and so far as we can tell, the processes of these

590

PHYSIOLOGY

cells do not grow together but simply remain in contact. Thus
the axis-cylinder of an anterior cornual cell ends on a muscle-
fibre as an arborisation, the branches of which end freely
on the surface of the fibre. The cells of the central nervous
system are influenced in the same way. An axon from the
periphery or from another part of the central nervous system
ends in an arborisation in contact either with the cell-body or
with the dendritic processes (Fig. 270). Any im^mlse arriving

Fig. 270.

Arborisation of collaterals from the posterior root-fibres round
the cells of the posterior horn. (Ramon y Cajal.)

at this arborisation sets up a new impulse in the cell-body,
just as a motor impulse descending a nerve sets up a new
excitatory impulse in the muscle with an energy considerably
in excess of the original nerve-impulse. Thus the whole
nervous system can be regarded as made up of a numberless
array of nerve-cells with their processes (we«?-o??s), the activity
of each being regulated by the connections of its dendrites and
the destiny of its axon. It is possible that the office of each
cell is not merely to transmit the disturbance arriving at it, but

THE SPINAL COED

591

to send it on with increased energy, acting like a battery relay
in a telegraphic circuit. In all cases where there is a distinction
between the dendrites and the axon, the direction of conduc-
tion seems to be in the dendrites towards the cell, cellulipetal,
and in the axon away from the cell, celluHfugal. In bipolar
cells, as in the spinal ganglia, it is impossible as a rule to
draw any distinction between the two processes.

If the nerve-cells serve as relays of energy, nervous
activity must be associated with a using up of material in
the cell ; and many attempts have been made to discover his-
tological evidences of nerve-cell activity. Of importance in

Fig. 271.

Cells from the oculomotor nuclei thirteen days after section of
the nerve on one side, a, cell from healthy side ; b, cell from
side on which nerve was divided (Flatau).

this connection is the presence ivf the nerve-cells of certain
bodies which are known as Nissl's granules. If a section of
nervous tissue fixed with alcohol, formol, or corrosive sublimate
be stamed with basic dyes such as methylene blue or toluidin
blue, the bodies of the cells are seen to contain a number of
coarse angular granules or masses arranged more or less
symmetrically round the cell, and extending for a considerable
distance along the dendrites (Fig. 271, a). The axon and that
part of the cell from which it arises (the nerve-hillock) are
quite free from these granules (cf. Fig. 269). As the result of
stimulation, changes have been described both in these granules

592 PHYSIOLOGY

and in the nucleus of the cell. Of more practical importance
however are the changes produced in these granules by
section of the axon itself. As a matter of fact, although
division of an axon causes the more profound changes in that
part which is separated from the cell-body or 'perikaryon, the
temporary or permanent loss of function does not leave the
cell unaffected. It was long ago shown that amputation of
a limb was followed after many years by a shrinkage and
atrophy of all that portion of the grey matter from which
the nerves to the limb were derived. The introduction of
Nissl's method has shown that an appreciable change is
produced within a few weeks, the granules losing their indi-
viduality and becoming broken up, so that the whole cell
takes on a diffuse blue stain (Fig. 271, h). This change is
followed after some considerable time by a gradual atrophy
of the cell and all its processes. It is sometimes spoken of
as secondary, or better as ' retrograde ' degeneration.

The grey matter is thus made up of nerve-cells embedded
in a close felt-work of fibres of various descriptions, fine
meduUated nerve-fibres coming in as collaterals from the
surrounding white matter and breaking up into naked
arborisations. Branching axis-cylinders, which begin and end
in the grey matter itself, as well as the richly branched
dendrites of the various nerve-cells, all these elements are
embedded in and supported by the special connective tissue
of the nervous system, the neuroglia.

The neuroglia resembles the rest of the nervous system
in being of epiblastic origin. The cells forming the primitive
neural groove are of two kinds, the neuroblasts, from which
the nerve-cells are derived, and the spongioblasts. These
latter at first form a continuous lining of the central canal,
and send out one process to the periphery of the cord.
This process branches freely, and in course of time some of
the cells wander out into the substance of the cord and
acquire many processes, which run out in all directions and
cross those of adjacent cells. In the adult cord the cell-
bodies of these neuroglia cells either disappear altogether or
are reduced to little more than the nucleus, so that the
neuroglia consists of a rich felt-work of branching fibres
crossing each other in all directions and forming a framework
for the nervous elements of the cord.

Fig. 272.

Cervical.

Dorsal. \

Lumbar

ANTERIOR
ROOT BUNDLCS

Sections of human spinal cord from the lower cervical, mid-dorsal,
and mid-lmnbar regions, showing the principal groups of nerve-
cells, and on the right side of each section the conducting tracts
as they occur in the several regions (magnified about 7 diameters).
(E. A. Schafer.) a, 6, c, groups of cells of the anterior horn ; d, cells
of the lateral hour ; e, middle group of cells ; /, cells of Clarke's
column ; g, cells of posterior horn ; c.c, central canal ; a.c, anterior
commissure.

38

694 PHYSIOLOGY

In accordance with its epiblastic origin, the neuroglia presents no chemical
resemblances to the group of connective tissues. Its main constituent is a
body allied to keratin, known as neuro-keratin, giving all the reactions of
proteins, but distinguished from the ordinary members of this group by its
insolubility in the digestive juices as well as by the high proportion of sulphur
in its molecule.

This neuroglia, thoiigli extending through the whole cord,
is especially concentrated at two points, viz. in the immediate
vicinity of the central canal and at the head of the posterior
horn, where mingled with small nerve-cells it forms a sort
of cap to the grey matter and is known as the substantia
gelatinosa of Rolando.

The grey matter of the cord may be considered as a con-
tinuous tube formed by the fusion of a series of paired
ganglia, each of which innervated one body segment. This
regular arrangement has been modified by the development
at a later period of the limbs, and the necessary growth of
new cells to supply the limbs. Hence we find a considerable
enlargement of the grey matter in two situations, the cervical
enlargement correspondmg to the brachial plexus, and the
lumbo-sacral enlargement which gives origin to the nerves of
the hind limb.

The cells of the grey matter are arranged in definite
groups or columns, some of which extend throughout the
whole length of the cord, whilst others are confined to certain
regions. These columns are —

1. In the anterior cornu, two sets of cells, the anterior or
median and the external groups. These cells are the largest
in the cord ; they have many processes, one process being
continued into the medullated nerve-fibre of an anterior root,
the other processes (dendrites) breaking up into a fine mesh-
work of non-medullated fibrils, which become lost in the
meshwork of the grey matter. The external group {b, Fig. 272)
is especially connected with the motor nerves to the limb
muscles.

2. The lateral column or intermedio-lateral tract, chiefly
marked in the dorsal and upper part of the lumbar spinal
cord. These cells are almost certainly connected with the
visceral outflow which occurs in this region. Their axons
pass out by the anterior roots, and then by the white rami
communicantes to the sympathetic system, in some ganglion
of which they terminate.

3. The cells of the posterior horn, small multipolar cells.

THE SPINAL CORD

595

4. Clarke's column or posterior vesicular column (Fig.
2'il%f), reaching from the seventh or eighth cervical nerve to
the third lumbar nerve, and represented opposite the second
and third cervical nerves by a small group of cells and possibly
also in the sacral region by a group known as Stilling's nucleus.
The cells composing this column are large and fusiform, with
their long axes parallel to that of the cord, so that in cross-
section they have the appearance of small round cells.

.pot

Fig. 273.
Direct pyram/ri^^^

Ant. lat

asc.tra£t

Direct

Cerebellat

Z-PosteriorJtoots.
with collaterals.

Spinal cord (after Lenhossek).

On left side of figure are shown the nerve-cells with their axis-cylinder
processes. On the right side the distribution of the chief collaterals.
1. Motor cells. 2. Cells of the columns. 2a. Cells of Clarke's column,
sending processes across into direct cerebellar tract. 3, 4, and 5.
Commissural cells.

A more general classification of the nerve-cells may be
based on the destmation of their nerve-fibre processes (Fig.
273). In this way we may distinguish —

(1) Motor cells. These are the large cells already de-
scribed in the anterior cornua. Their axis-cylinder processes
all run out into an anterior nerve-root, and end for the most
part in the motor end-plate on a muscular fibre.

(2) Cells of the columns. The nerve-processes of these
run out into the white matter, and the majority ascend
in one of the columns of the cord. We find these cells
in the anterior and lateral cornua, sending fibres into the
anterior and lateral columns. There are also a few in the

596 PHYSIOLOGY

posterior corniia which send their processes into the posterior
columns. The best-marked group however is that ah'eady
described as forming Clarke's column. These send their nerve-
fibre processes right across the grey matter into the lateral
column of the same side, where they turn upwards, forming a
distinct tract of fibres — the direct or posterior cerebellar tract.
(3) Commissural cells. This class embraces a number of
cells of different sizes and shapes. Their axons either end
in the grey matter of the same side, or traverse the cord to
form connections with the grey matter of the other side.
Many of these fibres pass through the anterior white com-
missure. Among these we find the Golgi type of cell, i.e.
a cell whose axon begins to divide almost immediately after
leaving the cell, and branching profusely ends in the near
neighbourhood of the cell from which it started.

The White Matter of the Cord

The white matter consists almost exclusively of medullated
nerve-fibres, which run for the most part longitudinally.
They are of various sizes, some of the smaller fibres being
branches (collaterals), which have been given off from the
larger ones, and which will shortly turn into the grey matter.
In section they resemble closely the fibres of an ordinary
peripheral nerve, but they differ from these in that they have
no primitive sheath or neurilemma. Each consists simply of
an axis-cylinder surrounded by a thick medullary sheath, the
whole embedded in a tube formed by the neuroglia. The
white matter is divided by the anterior and posterior fissures,
and the nerve-roots into anterior or ventral, lateral, and
posterior or dorsal columns. A further subdivision of the
anterior column into antero-median and antero-lateral, and
of the posterior column into postero-median and postero-
lateral, is indicated by slight grooves on the surface of the
cord in the cervical region. In order however to arrive at a
knowledge of the origin, course, and destiny of the fibres
composing the white matter, we must have recourse to indirect
methods. The following methods may be employed :

1. Wallerian method. If the cord be cut across trans-
versely, some tracts of white matter will degenerate in the
cord above the lesion (ascending degeneration), while other
tracts will degenerate in the cord below the lesion (descending
degeneration), according as the cells of origin of the fibres

THE SPINAL CORD 597

lie below or above the lesion. In this way the white matter
may be divided mto ascending and descending tracts.' This
method may be applied in two ways. The spinal cord may
be cut and the animal kept alive for three to six months.
At the end of this time all the degenerated fibres have dis-
appeared and their place is taken by nem-oglia. On staining
sections with carmine, the degenerated part therefore looks
pinker than the rest of the section. A better method is to
treat the sections by some process such as Weigert's, which
stains the normal medullary sheaths black. By this treatment,
the degenerated area is at once detected by its failure to take
the stam.

This method will not serve to display the presence of
isolated degenerated fibres among a mass of normal fibres.
For this purpose we may use Marchi's method, which is based
on the fact that the medullary sheath, when it breaks up,
undergoes chemical change, and acquires the composition of
ordinary neutral fat. If a tissue be placed in Miiller's fluid
for a fortnight, and then in a mixture of osmic acid and
Miiller's fluid, no blackenmg of the normal medullary sheath
is produced, although fat is blackened by the osmic acid in
the ordmary way. The presence therefore of one or two
degenerated fibres in a section of spinal cord will be at once
evinced by the appearance of black dots in the otherwise
unstained section. In employing this method, the cord must
be hardened before the broken-up medullary sheath has begun
to be absorbed, i.e. about two or three weeks after the lesion.

2. Method of retrograde degeneration. This is based on
the changes undergone by Nissl's granules (chromatolysis)
as the result of section of the axon of a cell. For example,
the hypoglossal nerve may be divided and three weeks later
the animal killed and sections of the medulla cut and stained
by Nissl's method. The distribution of the cells of origin of
this nerve is at once shown by the marked changes in the
cells on the side of the lesion as contrasted with the normal
cells on the opposite side (cf. Fig. 271, p. 591).

3. Developmental method (Flechsig). This method is

' A caution is here necessary. It is often assumed that a tract which
degenerates upwards is necessarily afferent in function, and vice versa. But
the result of section of a peripheral nerve, after which sensory as well as motor
fibres degenerate below the section, shows that the direction of degeneration is
not necessarily the same as the direction of conduction.

598 PHYSIOLOGY

founded on the fact that, when the nerve-fibres are first
formed in the foetal cord, they are non-meduUated, and the
different tracts of the cord acquire a medullary sheath at
different intervals, the pyramidal tracts being latest of all in
acquiring their sheath (Fig. 274).

4. Electrical method. The passage of a nerve-impulse
along the cord, as along a nerve, is accompanied by an
electrical change (current of action). It is possible to find
out by what path the electrical change travels, and thereby
to determine the path of the impulse of which the electrical
change is the concomitant (Gotch and Horsley).

Fig. 274.

r/x..

Section through the cervical spinal cord of a new-born child,
stained by Weigert's method, to show absence of niedullation
in pyramidal tract, ca, anterior commissure ; Fp, crossed
pyramidal tract ; Fe, direct cerebellar tract ; Zrp, posterior
root zone; rp', posterior root-fibres (Bechterew).

5. Experimental method. Different parts of the white
columns may be cut through, and the effects observed that
are produced in this way on the conduction of motor or
sensory impulses. Evidence in this direction is also furnished
by the clinical results of lesions of various parts of the cord.

By a combination of these methods the following con-
clusions have been arrived at. The white matter of the cord
may be divided into ascenduig and descending tracts (Fig. 275 ;
see also Fig. 272).

A. Descending tracts. — If the spinal cord be divided in
the cervical region, degeneration of two distinct tracts in the

THE SPINAL CORD

599

anterior and postero-lateral columns is produced. These are
the anterior or direct and the crossed pyramidal tracts. The
fibres composing these tracts are derived from the pyramidal
cells in the motor area of the cerebral cortex, and are there-
fore found degenerated if the motor area of the cortex is
destroyed. The crossed pyramidal tracts are derived from
the other side of the cerebral cortex and have crossed the
middle line at the lower part of the medulla, at the pyramidal
decussation. The anterior tracts contmue the course of the
pyramids in the medulla for a time, but cross gradually by
the anterior commissure on their way down the cord. Fmally,

al.asc.

Diagram of spinal cord. a.r. Anterior spinal nerve-roots, p.r.
Posterior root. a.py. Anterior pyi-amidal tract, l.py. Lateral
pyramidal tract, d.cbl. Direct cerebellar tract, p.m.c. Posterior
median cokimn. p.e.c. Posterior external column, al.asc.
Antero-lateral ascending tract.

therefore, all the fibres reach the crossed pyramidal tracts.
They end in the spinal cord by turning into the grey matter,
where they break up into a fine bunch of fibrils in close
connection with the motor cells of the anterior cornua (or,
according to SchJifer, with the cells of the posterior cornua).
On their way down the cord they give oii" fine side branches
or ' collaterals,' which run into the anterior cornu and there
terminate, thus establishing connections between one cortical
cell and the anterior cornual cells of several diflerent seg-
ments of the spinal cord. It is therefore concluded that
they carry motor impulses from the cerebral cortex to the
ganglion cells of the cord. Destruction of these columns by
disease or otherwise causes the abolition of voluntary control
over the muscles.

600

PHYSIOLOGY

Ventrally to the pyramidal tracts there is a fairly compact group of fibres
which degenerate downwards. This is known as the pre-pyramidal or rubro-
spinal tract, since its fibres can be traced up to the cells in the red nucleus,
a mass of grey matter in the mid-brain situated ventrally to the nucleus of the
third nerve.

There are also some scattered fibres in the antero-lateral
column, which degenerate in the downward direction. These
were formerly supposed to be derived from the cerebellum of
the same side, but it has been shown that they are in all
probability derived from Deiters' nucleus in the medulla,
which stands as a downward transmitting station between

Fig. 276.

spL

Diagram (from Schafer) showing the ascending (right side) and the
descending (left side) tracts in the spinal cord.
1. Crossed pyramidal. 2. Direct i^yramidal. 3. Antero-lateral
descending. 3a. Spino-olivary descending (bundle of Helweg).
4. Pre-pyramidal (rubrospinal). 5. Comma. 6. Postero-mesial.
7. Postero-lateral. 8. Lissauer's tract. 9. Dorsal (ascending)
cerebellar. 10. Antero-lateral ascending, s.m. Septo-marginal.
s.p.l. Dorsal root zone. a. Anterior horn cells, i. Intermedio-
lateral horn. p. Cells of posterior horn. d. Clarke's column.
The fine dots represent the situation of the ' internuncial '
or 'endogenous ' fibres of the|spinal cord.

cerebellum and cord. These are sometimes known as the
vestibulo-spinal tract.

Beside these tracts there is a little collection of fibres in
the posterior columns which degenerates for a few segments
of the cord heloio a transverse lesion (the ' comma ' tract).
They consist largely of fibres derived from the posterior roots,
which divide into ascending and descending branches as they
enter the cord, but also contain probably certain fibres derived
from cells in the cord and serving to connect one segment
of the cord with another.

Fig. 277.

,cere!bral cortex

CEREBELLAR
HEMISPHERE

Diagram showing the course, origin, and termination of the principal
tracts of the spinal cord (Schiifer).
' Descending tracts.'— la. A fibre of the crossed pyramidal tract, lb.
An uncrossed fibre of the pyramidal tract passing to the lateral
column of the same side. 2. A fibre of the direct pyramidal
tract. 3. Antero-lateral descending tract. 4. Pre-pyramidal
tract. 5. Comma tract. ' Ascencliufj tracts.'' — 6. Postero-mesial.
7. Postero-lateral tract. 9. Dorsal cerebellar. 10. Antero-lateral
ascending, m. Motor nerve fibre, s. Sensory roots.

602 PHYSIOLOGY

B. Ascending tracts. — The tracts which degenerate in the
cord above a transverse section are four in number :

1. The postero-median, as far up as the nucleus gracilis
in the medulla.

2. The posterior root-zone for one or two segments above
the lesion.

3. The direct or posterior cerebellar tract as far as the
cerebellum.

4. The antero-lateral ascending tract or anterior cerebellar
tract. The fibres of this tract also end in the cerebellum
near those of No. 3, but take a more circuitous path than
those of the latter tract.

Division of all the posterior roots on one side causes
degeneration of the posterior root-zone and postero-median
column on the same side, as well as of some fibres in the
* comma ' tract. Hence the fibres of these columns have
their trophic centres on the ganglia of the posterior roots.
The other two ascending tracts do not degenerate after section
of the posterior roots, and must therefore have their trophic
centres in the cells of the grey matter of the cord. We have
already mentioned that the direct cerebellar tract is derived
from the cells of the posterior vesicular column of Clarke,
and it has been stated that the antero-lateral ascending tract
also originates in the same way. All these tracts, on their
way up the cord, send off branches or collaterals which
terminate round the cells of the grey matter in the different
segments of the cord. Some of these run from the posterior
root-fibres directly across to the anterior cornu of the same
side, and thus subserve the simplest forms of reflex action
(cf. Figs. 273 and 276).

The deeper parts of the white matter, near the grey
matter, in the anterior and lateral columns, are known as the
ventral and lateral basis bundles. They contain fibres, some
ascending, some descending, which seem to connect different
levels of the cord, some fibres of which can be traced from
the cervical to the lumbo-sacral region. Besides these 'inter-
nuncial ' fibres, there is a large number of fibres in the white
matter which do not degenerate more than one spinal segment
either above or below a transverse section of the cord. These
are supposed to be commissural, serving to connect one
segment of the cord with the other.

THE SPINAL COED 608

Section 2
PATHS OF IMPULSES IN THE COED

All impulses which pass through the cord form parts of
reflex actions, carried out either by the cord alone, or with
the intervention of the higher parts of the central nervous
system, the bulb, cerebellum, or cerebral hemispheres. We
may therefore conveniently distinguish the local spinal re-
flexes from the brain reflexes, including the complex ones
involving conscious sensation and volition. All these reflexes
are inaugurated by afterent impulses, which reach the central
nervous system along sensory nerve-roots.

The posterior spinal (sensory) roots at their entrance into
• the cord divide into two bundles. The smaller of the two,
situated more laterally and consisting of fine fibres, enters
opposite the tip of the posterior horn and turns up at once in
Lissauer's tract, a bundle of fine longitudinal fibres lying close
to the periphery of the cord. The fibres seem to pass into
and end in the substance of Rolando. The larger median
bundle of coarse fibres passes mto the postero-external column.
Here each fibre divides into a descending and an ascending
branch, the former running in the comma tract, the latter in
the posterior columns up as far as the gracile and cuneate
nuclei of the medulla. Both of these branches give oft' col-
laterals in the whole of their course, most numerous near the
point of entry of the nerve. These collaterals may be divided
into four sets according to their destination.

1. Fibres ending round cells of anterior horn on same
side or crossing by posterior commissure to grey matter on
other side.

2. Fibres ending in grey matter of posterior horns.

3. Fibres ending round cells of Clarke's column.

4. Fibres to lateral horn.

Since the motor nerves arise from the anterior horn cells,
the first set, the so-called sensori-motor collaterals, represent
the shortest possible spinal reflex path. The second group may
also represent a spinal reflex path with two relays of cells, and
therefore greater choice of response and longer reaction time.

The third set puts into action the cerebellar tracts which
arise from the cells of Clarke's column, and therefore call into
play a much more complicated mechanism, the limits of whose
action it would be difficult to define. The collaterals to the

604 PHYSIOLOGY

lateral horn probably represent the afferent tracts of the various
visceral and vaso-motor reflexes which we studied in the earlier
chapters.

In dealing with the reflexes involving the co-operation of
the brain we find no special tracts devoted to those impulses
which affect consciousness as sensations. All tracts going
towards the cerebral hemispheres are interrupted by cell re-
lays in the medulla or cerebellum, and must serve as afferent
channels for unconscious as well as for conscious reactions.
The quality of an afferent impulse can only be defined by its
origm, or by its effect on consciousness ; and much discussion
has arisen as to the exact path of the various cutaneous and
muscular sensations in the cord.

It is evident that an impulse may travel to the cortex by
way of the two cerebellar tracts through the cerebellum, or by
way of the posterior columns through the intermediation of the
bulbar nuclei, or by a series of relays from one segment of the
cord to another through grey and white matter alternately.

It is supposed that all of the ascending tracts may con-
vey afferent impulses from the posterior roots to the brain,
although evidence as to the part taken by each tract is very
conflicting. The following account represents the views
which may be regarded as the most probable (Page May) :
Pain impulses, on entering the cord by the posterior roots,
cross to the other side at once, and then pass up, chiefly in
the antero-lateral ascending tract of Gowers, as far as the
optic thalamus. Sensations of heat and cold take a very
similar course. Hence they are generally affected by lesions
of the cord in the same way as pain sensations. Impulses of
touch and pressure, after entering the cord, pass up in the
posterior column of the same side for four or five segments, then
cross gradually and pass up in the opposite anterior column.
Muscular sensibility, including the impulses from joints and
tendons, take two courses. Those which do not reach con-
sciousness, and are involved in the involuntary guidance of
muscular movements, run up chiefly in the anterior and
posterior cerebellar tracts of the same side. Those which
furnish the material for conscious sensations and give
information as to the position of the limbs, &c., are entirely
homolateral, and travel up in the posterior columns of the
same side of the cord. All impulses which reach the brain
cross finally to the optic thalamus and thence to the cortex of
the opposite side.

THE SPINAL COED 605

Hemisection of the cord on one side causes paralysis of
the same half of the body below the lesion. Muscular sensi-
bility is also destroyed on this side. On the other side of
the body, sensation to heat, cold, pain, and partial^ to touch,
is destroyed. The sensory disturbances however rapidly pass
off, and in animals the spinal cord can be hemisected alter-
nately on right and left side at three dijBferent levels without
causing a lasting anesthesia, showing that in the absence of
the direct paths the sensory impulses may zigzag up the cord
and finally reach their destination and affect consciousness.

The only direct unbroken cortico- spinal fibres are those
contained in the pyramidal tracts. Motor impulses, which
start from the cerebral cortex on one side, pass down that
s;de till they reach the lower part of the medulla. Here the
greater number of the fibres cross over in the pyramidal
decussation to run down in the crossed pyramidal tract on
the other side of the cord. The few fibres which do not cross
over in the pyramidal decussation are continued as the direct
or anterior pyramidal tract. These however also cross to the
other side in their passage down the cord before becoming
connected with the anterior cornual cells. Hemisection
therefore of the spinal cord in the dorsal region will produce
paralysis of motion and loss of or impaired sensation in the
parts supplied by the nerves on the same side below the lesion.^

A great part of the white matter of the cord is concerned
then in maintaining connection between the brain and higher
parts of the nervous system and the periphery, through the
intermediation of the cells of the grey matter of the cord.
Corresponding to this function we find a gradual increase in
the number of fibres in the white matter as we ascend from
the. sacral part of the cord to the medulla, the white matter
being continually reinforced as it ascends the cord by fibres
establishing connection witli the ganglion cells forming the
nuclei of the nerve-roots.

Vaso-motor impulses to the limbs travel down the lateral
columns of the cord on the same side.

' It has been recently stated by Sebafer that the pyramidal fibres end, not
in the anterior cornua but round the cells of the posterior cornua. If this be
confirmed, it would show that the cortex affected the spinal motor apparatus
by attacking its sensory rather than its motor side, so as to save a multiplication
of co-ordinating mechanisms.

606 PHYSIOLOGY

Section 3
THE COED AS EEFLEX CENTEE

In the lower animals, such as the frog, the spinal cord of
itself is able to carry out many complex reflex actions. If
the skin around the anus of a decapitated frog is stimulated,
a sudden extension of both legs is produced, so that the
animal leaps away from the stimulus. If a small piece of
filter-paper moistened with acetic acid be placed on the inner
side of the right thigh, the right foot will be raised and
used to wipe away the offending object. If the right leg be
held or be cut off, after various fruitless endeavours to re-
move the irritant with this limb, the left leg may be raised
and used for this purpose. These and many other similar
experiments show that the spinal cord, separated from the
upper part of the nervous system, is capable in the frog of
bringing about many highly complex co-ordinated move-
ments, which are apparently purposive, i.e. they seem to have
a definite object in view ; and arguing from experiments,
such as the second one we have mentioned, it has been thought
that psychical phenomena may accompany these reflex actions.
But it must be remembered that summation of afferent im-
pulses occurs just as summation of stimuli applied to a frog's
ventricle. A single stimulus, too weak to evoke a reflex
contraction, may do so if repeated several times. In our
experiment, the right leg being unable to remove the offend-
ing object, stimulation goes on, and the effect is summated
until it is strong enough to spread to the other side of the
cord and so set the left leg in motion.

The time taken up in the transmutation of afferent into
efferent impulses in the spinal cord may be estimated by
measuring the interval that elapses between stimulation of a
sensory nerve with a single induction-shock and the resulting
muscular contraction, and subtracting from the amount so
determmed the time taken in the passage of the impulse up
and down the nerve-fibres and the latent period of the
muscle, the contraction of which is recorded. The reflex
time or ' reduced reaction time ' measured in this way is
found to be about 0*01 second.

THE SPINAL COED 607

A slight stimulus causes reflex contraction only of the
limb stimulated. A stronger stimulus causes contraction of
the corresponding limb of the other side also, and the effect
of a still stronger stimulus may extend to the other two
limbs. With this resistance to passage of impulses in the
cord across the middle line and longitudinally from one
segment to another, we find a corresponding increase in the
reflex time.

Effect of strychnine. — If strj^chnine be injected into the
dorsal lymph -sac of a frog, the spinal cord is so affected that
the normal resistance to passage of impulses is abolished.
The slightest stimulus of the skin now evokes a maximal reflex
action, there being no longer any proportionality between the
magnitude of the stimulus and that of the reflex effect pro-
duced. The minimal reflex time is not diminished, but the
smallest stimulus can travel equally well in all directions in
the cord. Hence the slightest touch of the skin sends all
the muscles mto prolonged tetanic contraction, and the frog
becomes stretched out with its limbs stiff and rigid.

It has been shown by Sherrington that the most characteristic point about
the action of strychnine is that this drug converts inhibitory into motor
reflexes. Tlius when flexion of the knee is excited by stimulation of the pad
of the foot, this movement involves not only contraction of the hamstring
muscles but also relaxation of the extensors of the knee. After injection of
strychnine a similar stimulus applied to the foot causes simultaneous con-
traction both of extensors and flexors, all the inhibitory phenomena of every
co-ordinated muscular reaction being abolished by the drug.

Inhibition. — The reflex action normally following a slight
stimulus of any part of the body may be completely i)re-
vented or inhibited by strong sensory stimulation of some
other part. If the optic lobes of a frog be stimulated by
putting a crystal of salt on them, or the central end of the
right sciatic nerve by means of a farad ic current, stimulation
of the skin of the left leg with acid produces no effects
whatever. A striking parallel instance of this occurs in our
daily mental life. Concentration of the attention in any one
direction, either by severe pain or through psychical excite-
ment, causes similar stimuli to be quite unheeded, so that in
battle a man may be unaware that he is severely wounded
until he feels faint or sees blood flowing. We may say,
putting the phenomena of the spinal cord into terms of con-
sciousness, that its ganglion cells are so much occupied with

608 PHYSIOLOGY

the stronger stimulus that they do not notice a weaker
stimuhis applied to some other part.

Spinal Beflexes iji Higher Animals

When we come to the highest animals— monkey and man
— there seems to be a striking difference between their spinal
cord and that of the frog, in that the reflex actions, which
can be carried out by the cord severed from the medulla and
brain, are limited to those of the simplest nature. If a man
has had his cord crushed in the dorsal region, tickling the
soles of his feet will cause him to draw up his legs, although
he is perfectly unconscious that his feet are being touched.
But beyond one or two simple reflexes of this description,
the spinal cord seems to have no power of carrymg out
co-ordinated acts. It is however difficult in these cases, and
in experiments on the spinal cord in mammals, to eliminate
the effects of shock. After total transverse section of the
spinal cord high up, the animal is in a condition of shock,
which lasts a considerable time ; his vital activities are pro-
foundly depressed, and it may be impossible to evoke even
the simplest reflex action by stimulation of any sensory sur-
face below the lesion. But if the experiment be carefully
conducted, and the animal be kept alive for a considerable
time, the cord little by little recovers its powers, and we then
find that the spinal cord of the dog can carry out the most
complicated reflex movements without any connection with
the higher centres. In a dog whose cord has been divided
in the dorsal region, the reflex movements required for
micturition, defsecation, impregnation, and parturition may
be normally carried out. If the dog, which usually squats
on the ground owing to the paralysis of its hinder extremities,
be raised on its hind legs by the hands being placed under
the fore-legs, and given a little push forwards, the animal
may run along for a few steps before it collapses again into
a sitting posture. In this case the reflex runnmg movements
of the hind legs, carried out by the separated spinal cord,
are started by the sudden stretching of the anterior thigh
muscles.

The vascular tone in the lower part of the body, which is
ost for some time after the operation, is also regamed.

Muscular tone. — Every muscle in the body is normally in

THE SPINAL COED 609

a condition of slight continued contraction, which is known
as muscular tone. If a frog with intact spinal cord l)e sus-
pended by the jaw, and the nerves going to the lower limb
be cut, this limb will hang down straighter than the other in
consequence of the abolition of its muscular tone. The same
result may be produced if, instead of dividing all the nerves
of the limb, only the sensory or only the anterior roots of
those nerves l)e divided. This shows that muscular tone
is reflex, and depends for its maintenance on the intact con-
dition of afferent paths, centre, and efferent paths. On the
presence of this tone depends the phenomenon known as
' tendon-reflex ' or knee-jerk. If the leg be allowed to hang
loosely and the patellar tendon be struck, the extensor
muscles of the thigh contract and raise the leg. This con-
traction is probably due to the direct stimulation of the
muscle by the sudden stretching produced on striking its
tendon. If the muscle has lost its tone by disease of the
spinal cord, or through section of the afferent or efferent fibres,
striking the tendon will no longer stretch the flabby muscle,
and the tendon-reflex will be abolished. The mere stretching
however is not the only factor, since under these conditions
no knee-jerk is produced, however much the muscle may be
passively stretched. The impulses descending the nerves
to the muscles seem to keep them in a state of wakefulness,
ready to respond to the slightest local stimulus. The cha-
racters of these reflex tonic impulses are much affected by
the influence of other afferent stimuli. Especially interestmg
is the relation shown by Sherrington to exist between the
tonic condition of antagonistic muscles, e.g. between the
hamstrings and the vastus internus of the quadriceps extensor
muscle. Section of the hamstrmg muscles (so as to relax
them), or even section of their nerve, causes at once great
increase in the jerk elicited by tapping the patellar tendon.
On the other hand the knee-jerk is at once abolished by
stretching the hamstring muscles, or by weak stimulation of
the central end of the cut nerve to the hamstrings (Fig. 278).
Every sensory stimulus which evokes contraction of one set
of muscles will therefore produce inhibition of the antago-
nistic set.

Very great exaggeration of the tendon phenomenon is ob-
served in cases where the pyramidal tracts are degenerated,

39

610 PHYSIOLOGY

and indicates a heightened reflex excitabihty of the lower
spinal centres, perhaps reinforced hy impulses from the cere-
bellum.

The value of the tendon phenomena as a means of dia-
gnosis has tended to obscure their great importance in the
normal individual. Every joint is protected by inextensible
ligaments and by muscles. A sudden strain on a ligament
either will have no effect, or will rupture some of its fibres
and perhaps injure the adjacent joint surfaces. An ordinary

Fig. 278.

L.3

Ant? crur .n.

Diagram to show muscles and nervei3 concerned in Sherrington's
experiment on tlie reciprocal innervation of antagonistic
muscles. L.3, L.4, L.5, third, fourth, and fifth lumbar roots;
S.l, S.'2, first and second sacral roots.

reflex contraction would be powerless to prevent this, since
the mischief would be done before the reaction could take
place. But the central nervous system confines itself to
keeping the muscles awake, so that they themselves may
react to any sudden increase in their tension by an equally
sudden contraction, which saves the joint before the central
nervous system has even become aware of the strain.

Co-ordmation of Movements hy the Cord. — Since the act
of stretching a muscle in a normal state of tone acts as an
excitant, and causes increased tone or even contraction, every

THE SPINAL COED 611

movement of a limb, by putting the muscles, antagonistic to
the movement, on the stretch, would tend to prevent the
carrying out of the movement. Thus flexion of the knee
would stretch the extensor muscles and thus increase their
tone and resistance to the movement of flexion. Sherrington
has shown however that every movement of a limb, worked
reflexly, involves not only the contraction of the muscles
eftecting the movement, l)ut also a simultaneous inhibition of
tone and relaxation of the antagonistic muscles, and this
occurs in the ' spinal animal,' i.e. in one whose spinal centres
are entirely cut oft' from the brain. Thus a ' painful '
stimulus, such as the prick of a needle applied to the pad of
the foot, causes retraction of the foot, and this movement
involves contraction of the flexors and relaxation of the
extensors of the limb. On the other hand gentle pressure
applied to the pad causes inhibition of the flexors and con-
traction of the extensors, so that the limb is extended.

The reflex extends also to the other side of the cord, but
here the eftbrts are reversed : extension of the stimulated
limb being associated with flexion of the opposite limb, i.e. the
ordinary association of movements involved in the diagonal
action of the limbs in progression.

The spinal cord is thus able to carry out co-ordinated acts
of considerable complexity, these acts being adapted to the
character and situation of the stimulus, and also to the
previous state of activity of the cord and of the muscles
involved.

Other reflex functions of the cord are concerned with the
carrying out of the following actions : —

Micturition.

Defaecation.

Impregnation and parturition.

Vascular tone.

612 PHYSIOLOaY

CHAPTER XV

THE BRAIN

Section 1
THE RTRUCTUEE OF THE BRAIN

The physiology of the brain falls naturally into two main
divisions, viz. — the cerebral hemispheres, and the rest of the
brain, including medulla, pons, iter, and corpora quadrige-
mina, and third ventricle.

This second part may be considered as a prolongation of
the spinal cord forwards, consisting like this of a central
tube of grey matter, surrounded by a tube of white matter.
Owing to the importance and complex connections of the
nerve-roots which arise from this part of the neural axis
(cranial nerves), the typical division of grey matter into
cornua becomes lost ; and we find that, while some nerves
take their origin from the central tube of grey matter, in
other cases the collection of cells forming the nucleus has
become more or less separated from the central axis.

Moreover masses of grey matter, which have no repre-
sentative in the cord, make their appearance in the white
matter.

The roof of the neural canal, which over the third ven-
tricle and the posterior part of the fourth is greatly thinned,
consisting merely of a layer of epithelial cells, is thickened
over the iter (second cerebral vesicle) to form the corpora
quadrigemina, and over the pons and anterior part of the
fourth ventricle it grows out into a large excrescence with
complicated structure— the cerebellum fcf. Fig. 285). Cover-
ing the corpora quadrigemina and cerebellum is a layer of
grey matter outside a central mass of white fibres. The
lateral walls of the third ventricle (first cerebral vesicle) are
thickened to form the optic thalami, which contain masses

THE i3RAIN

613

of grey matter. The cerebral hemispheres are formed by
hollow outgrowths from the first cerebral vesicle. These in
course of development become as large as the whole of the
rest of the brain put together, and grow backwards over the
rest of the brain as far as the middle of the cerebellum
(Figs. 9, 10, pp. 16, 17). Their upper walls become very much
thickened, and consist of white matter internally and grey
matter externally. Their lower walls remain as a thin layer
of undifferentiated epithelial cells ; this becomes closely
applied to the epithelial layer forming the roof of the third

Human brain viewed from the bide, to display the various divisions
(Quain). A, cerebral hemisphere ; B, cerebellum ; C, pons
Varolii ; D, medulla oblongata ; a, crura cerebri ; b, superior,
c, middle, and </, inferior peduncles of cerebellum.

ventricle, from which it is separated only by a process of the
pia mater carrying numerous blood-vessels (the velum inter-
positum). The lower and outer wall of the cerebral hemi-
spheres becomes very much thickened, and forms the corpus
striatum, which is closely applied to the front and outer part
of the optic thalamus. In it two masses of grey matter are
developed, the nucleus caudatus and nucleus lenticularis,
separated from one another by a layer of white fibres, which
is continuous with a similar layer separating the corpus
striatum from the optic thalamus, and is called the internal
capsule.

614

PHYSIOLOGY

It will be convenient to trace first the modifications under-
gone by the axial part of the nervous system in the brain,
and then to deal with the new masses of grey matter which
have no homologies in the spinal cord, as well as the long
tracts of white matter serving to connect different levels or
different sides of the brain.

In examining successive sections from the spinal cord
up through the medulla, the first change which makes
its appearance is due to the decussation of the pyramids

Bection IIuoukIi the lower bolder of the nieduUii oblongata, at
the pyramidal decussation (Bechterew). f.l.a. anterior fissure ;
cl, decussation of the pyramids ; V, anterior columns ; C.a,
anterior cornu ; cc, central canal ; S, lateral columns ; f.r,
formatio reticularis ; cc, neck, and g, head of the posterior
cornu; r.p.C.I, posterior root of first cervical nerve; n.c,
beginning of nucleus cuneatus ; n.cj, nucleus gracilis; H\
funiculus gracilis; H'-, funiculus cuneatus; s.l.p, posterior
fissure.

(Fig. 280). Throughout the spinal cord, fibres have been
crossing from one side to the other through the anterior
white commissure, many of them belonging to the pyramidal
system. But at the lower border of the medulla we see
a large mass of fibres crossing between the anterior columns
and the postero-lateral columns, at first cutting off the head
of the anterior horn and later on breaking this up altogether,
so that the only definite collection of grey matter left in this
situation is a small part of the lateral column of grey matter

THE BRAIN 615

known as the lateral nucleus. In this way are formed the
big anterior columns of the medulla, which are known as the
pyramids, and which contain all the fibres that in the cord
are represented by the direct and crossed pyramidal tracts.

The next change is due to the ending of the posterior
columns. It will be remembered that these are the central
ascending branches of dorsal nerve-roots, having therefore
an origin outside the cord. All the way up the cord they
send in collaterals to end in the grey matter of the posterior
horn. The main mass however terminates in the medulla
just above the pyramidal decussation in two collections of
grey matter —the nucleus gracilis and the nucleus cuneatus,
which seem to be formed by a great hypertrophy of the grey
matter at the root of the posterior horn. The effect of this
development in the dorsal region of the medulla is to push
the head of the posterior horn outwards. At the same time
this mass of gelatinous substance becomes enlarged, so that
in section we have three grey masses from within outwards,
the nucleus gracilis, the nucleus cuneatus, and the nucleus of
Kolando (Fig. 281).

With the disappearance of the posterior columns and the
development of the pyramids we get a practical obliteration
of the anterior fissure and a displacement of the central
canal towards the dorsal surface. A little higher up the
canal opens out altogether, forming the fourth ventricle,
covered on its dorsal surface only by a thin layer of epen-
dyma, a simple epithelium representing all that is left of
the dorsal wall of the primitive hind brain. The appearance
of the section is now modified by two structures. In the
first place a new mass of grey matter consistmg of a thin
layer shaped like a flask with its orifice directed inwards
(Fig. 282, o) is developed in the lateral part of the medulla,
between the pyramids in front and the tubercle of Rolando
behind. This is the olivary body, and has on its inner and
dorsal sides two other little grey masses which are the acces-
sory olivary bodies. The other feature is the new relay of
sensory fibres which start from the dorsal nuclei, the nuclei
gracilis and cuneatus. These fibres run outwards and for-
wards from the nuclei right round the medulla, some passing
superficially to the olivary body to join the restiform body of
the opposite side, while others pass deeply to the olives, and

616

PHYSIOLOGY

crossing in the median raphe turn upwards in the broken
mass of grey and white matter which Hes between the olives
and the superficial grey matter of the fourth ventricle.
Some fibres also pass into the restiform body of the same
side.

It will be remembered that the anterior half of the fourth
ventricle is covered in by the cerebellum, which is attached

nM.

Section of the medulla oblongata in the region of the superior
pyramidal decussation (Schwalbe). *. a.«t./., anterior median
fissure ; f.a., superficial arciform fibres emerging from the
fissure ; j^y., pyramid ; n.ar., nucleus of the arciform fibres ;
f.a.', deep arciform fibres becoming superficial ; o, lower end
of olivary nucleus ; o', accessory olivary nucleus ; n.l., nucleus
lateralis ; f.r., formatio reticularis ; f.a.-, arciform fibres pro-
ceeding from formatio reticularis ; g, substantia gelatinosa
of Kolando; a. F., descending root of fifth nerve; ii.c, nucleus
cuneatus ; 7i.c.', external cuneate nucleus ; f.c, funiculus
cuneatus ; n.g., nucleus gracilis; f.g., funiculus gracilis; p.m.f.,
posterior median fissure ; c.c, central canal surrounded by
grey matter, in which are n.XT., nucleus of the spinal ac-
cessory, and ii.XII., nucleus of the hypoglossal ; s.cl., superior
pyramidal decussation (decussation of fillet).

to the axial part of the brain hy three peduncles, the inferior
peduncle or restiform body, the lateral peduncles which form
the great mass of transverse fibres known as the pons Varolii,
and the superior peduncles which run forward to the pos-
terior corpora quadrigemina. The restiform bodies can be

THE BRAIN

617

regarded as the direct continuation forwards of the postero-
lateral columns of the cord, mi)ius the pyramidtil tracts, the
chief remaining tract therefore being the posterior or direct
cerebellar tract. In the region of the dorsal nuclei, however,
it receives accession of fibres from the gracile and cuueate

|) n.ar

bectioii of the inedulla oblongata at about the midclle of the
olivary body (Schwalbe). j. f.l.a., anterior median fissure ;
7i.ar., nucleus arciformis ; i), pyramid ; XII.. bundle of hypo-
glossal nerve emerging from the surface ; at b it is seen
coursing between the pyramid and the olivary nucleus, o ;
/.rt.c, external arciform fibres; «./., nucleus lateralis; a, arci-
form fibres passing towards restiform body, partly through the
substantia gelatinosa, </, partly superficial to the descending
root of the fifth nerve, a.V.; A', bundle of vagus root, emerg-
ing ; f.r., formatio reticularis ; c.»"., corpus restiforme. begin-
ning to be formed, chiefly by arciform fibres, superficial and
deep; Ji.c, nucleus cuneatus ; 7!. r/., nucleus gracilis; f, attach-
ment of the taenia ; /.s., funicuhis solitarius; nX, nX', two
parts of the vagus nucleus ; n.XII, h\-poglossal nucleus ; n.t.,
nucleus of the funiculus teres ; ii.am., nucleus ambiguus ;
r, raphe ; A, formatio reticularis alba; o', o", accessory olivary
nuclei ; o, olivary nucleus ; p.o.L, pedunculus olivaD.

nuclei of the same side and, through the superficial arcuate
fibres, from the nuclei of the opposite side, and thus passes
as a thick white bundle into the cerebellum. On its way it
is joined by a smaller bundle, the internal restiform body,
which conveys fibres from the vestibular division of the
eighth nerve and from Deiters' nucleus to the cerebellum.

618

PHYSIOLOGY

A section through the pons shows the fourth ventricle
widely dilated, with a floor formed of grey matter as in the
medulla. The chief difference in the appearance of the sec-
tion is due to the great masses of transverse fibres which
pass into the pons by the lateral peduncles of the cerebellum,
cross by the median raphe, and either turn upwards or down-
wards on the opposite side or end in connection with the

Section across llie pons at about the middle of the fourth ventricle
(Schwalbe). ~. pij. ijyramid bundles continued up from the medulla ; ^'o,
transverse fibres of the pons passing from themiddle crus of the cerebellum,
before (po^) and behind ( j»'-) the chief pyramid bundles ; t, deeper fibres of
the same set, constituting the trapezium ; the grey matter between the
transverse fibres is not represented ; r, raphe ; o.s., superior olivary
nucleus ; a.V, bundles of the descending sensory root of the fifth nerve
enclosed by a prolongation of the grey substance of Rolando ; VI, root
bundle of the sixth nerve; 7i. FJ, its nucleus; VII, root bundle of the
facial nerve ; Vila, longitudinal portion of the same ; n.VII, its nucleus ;
VIII, (superior) root of the auditory nerve; n.VIII, its nucleus; v,
section of a vein.

nerve-cells which are scattered throughout the white fibres.
The pyramids can still be seen as thick longitudinal bundles
on each side in the midst of the transverse fibres. Dorsall}"
to these transverse fibres is a special mass of grey matter
known as the superior olive. Even in the pons we can

THE BRAIN 619

divide the nervous mass, lying below or anteriorly to the
central grey matter, into two parts — the formatio reticularis
behind and the transverse fibres and pyramids in front. A
little further forward a section will escape the cerebellum
altogether, and will cut through the fourth ventricle, bounded
ventrally by the upper part of the pons and dorsally by the
thin mass of grey matter, the valve of Vieussens , (Fig. 283).
On each side will be seen the superior peduncles of the cere-
bellum, made up of fibres runnmg from cerebellum to posterior
corpora quadrigemma, as well as the continuation upwards
of the antero-lateral ascending tract, which passing up in
this peduncle bends dorsally round the fourth nerve, and

Diagrammatic transverse section tlirough mid-brain to show position of
fillet and pyramid. A.Q. Anterior corpus qnadrigeminum. d V. Descend-
ing motor root of fifth nerve. F. Fillet (I, lateial, and m, mesial fillet).
Pyr. Pyramid. Fr. Fibres from frontal lobe to pons. T.O. Fibres from
occipital lobe to pons. Ne. Fibres from nucleus caudatus to pons. III.
Boot of third nerve. S. Sylvian iter. En. Red nucleus.

running backwards ends in the superior vermis of the cere-
bellum.

A little further forwards the fourth ventricle comes to an
end, and the section passes through the mid-brain, the cavity
of the second cerebral vesicle being represented by the narrow
Sylvian aqueduct, bounded dorsally by the corpora quadri-
gemina and ventrally by the crura, the stalks of the brain.
The crura are divided by an irregular mass of grey matter,
the substantia nigra, into two parts. Anteriorly is the pes
or crusta, composed almost entirely of longitudinal white
fibres. The dorsal part, the tegmentum, is a direct prolonga-
tion forwards of the formatio reticularis of the medulla and

620

PHYSIOLOGY

pons, and like this contains much scattered gi'ey matter,
besides one large, more distinct mass known as the red
nucleus.

The cerebral axis comes to an end at the third ventricle,
which corresponds to the first cerebral vesicle. It terminates
in the following way : the roof ceases to exist, being reduced
to a mere layer of epithelium. The floor is also thinned, but
still contains nervous matter, forming the optic commissure,

Fig. 285.

for.M'

anav.Jisf.

irincal stria

infaiuhh

pit hoilij

Corp alb

posf. cotntn.
incal Iiodi^

tab. ualv.

Portion of a median section of the brain, showing the corpus
callosuni, third ventricle, iter or aqueduct of Sylvius, fourth
ventricle, cerebellum, pons, etc. (G. D. Thane.)

the infundibulum, and the corpora albicantia (Fig. 285). The
lateral wall however undergoes considerable development
and forms the great cerebral ganglion known as the optic
thalamus. From the front part of the first cerebral vesicle
the cerebral hemispheres have been developed, and in the
anterior and basal portion of these hemispheres a complicated
mass of grey matter, the corpus striatum, has been developed
in close proximity to the optic thalamus. As the crura cerebri
pass up, the tegmentum becomes continuous with the optic

THE BRAIN 621

thalamus and tissues of tlie subthalamic region, ^Yhile the
crusta diverging somewhat sweeps round the outer surface of
the optic thalamus, lying thus between the posterior part of
the corpus striatum (the lenticular nucleus) and the optic
thalamus. In front the fibres pass as a distinct layer through
the substance of the corpus striatum between the nucleus
lenticularis and nucleus caudatus of this body. The layer of
white matter is thus fan-shaped, and expands still further
after passing between the basal ganglia to be distributed to all
parts of the cortex of the cerebral hemispheres, forming an
important constituent of the white matter, the corona radiata,
underlying the superficial grey matter. The part between the
basal ganglia is known as the internal capsule {v. Figs. 286
and 287). The anterior and posterior parts (in horizontal
section) are inclined to one another, so that we can distin-
guish an anterior and a posterior limb, the junction of the two
being known as the genu.

The Axial Grey Matter

In the spinal cord we could distinguish between the
anterior grey matter giving origin to the motor nerves, the
posterior grey matter serving as an end-station for a number
of the sensory posterior root-fibres, and a lateral horn, less
well marked, probably giving origin to the visceral system of
nerves.

As the central canal widens out to form the fourth ven-
tricle, the relative position of these various parts becomes
altered, the anterior grey matter being now nearest the
median line, while the posterior grey matter lies more late-
rally. The lateral grey matter seems to lie deeper than the
rest, from which it is separated by a part of the tangle of
fibres and cells known as the form a tin reticularis.

AU the cranial nerves from the third to the twelfth arise
or end in the axial grey matter, or in close proximity to it.
So great however is the complexity of this part of the ner-
vous system, and so involved are the genetic relations of the
various nerves, that it is difficult or impossible in many cases
to state definitely the spinal analogies of the various nerves.

The cranial nuclei (of origin or termination) may be
roughly classed as follows :

622 PHYSIOLOGY

1. Motor nuclei, close to the middle line in floor of fourth
ventricle and iter. From below upwards we get definite
groups of large cells giving origin to the fibres of the hypo-
glossal, sixth nerve, fourth nerve, third nerve.

2. Sensory nuclei, i.e. first cell-stations of afferent fibres
having their trophic centres outside the cord. These lie
externally to the motor nuclei, and are represented ):)y the
combined nucleus of the glossopharyngeal, vagus, and acces-
sory, and also by the nuclei of the eighth nerve and the
sensory nucleus of the fifth, with its descending prolongation
in the suhstantia gelatinosa.

3. Nuclei of efferent neriies hclonging to tlie splanchnic
system. These lie more deeply at some distance from the
middle line, and include tlie nucleus ambiguus for the efferent
fibres of the vago-giossopharyngeal, the nucleus of the seventh
or facial, and probably the motor nucleus of the fifth nerve.

In a cross -section of the medulla at the pyramidal decus-
sation, before the central canal has opened out (Fig. 280),
two groups of cells are seen in the central grey matter.
The anterior of these consists of large multipolar cells, and
gives origin to the motor fibres of the hypoglossal nerve.
The posterior group is the lower end of a long column which
receives the end-arborisations of the afferent fibres of the
ninth, tenth, and eleventh nerves {glossopharyngeal, vagus,
and bulbar portion of sjnnal accessory).

In a section a little higher up, taken through the middle
of the olivary body (Fig. 282), the central canal has opened
out into the fourth ventricle, and the vago-glossopharyngeal
is now seen lying laterally to the hypoglossal nucleus. The
nerve-fibres connected with these nuclei pass out on either
side of the olivary body, the hypoglossal taldng the median
and the vago-glossopharyngeal the lateral position. The
fibres of these afferent nerves, like all others in the bulb or
cord, divide into ascending and descending branches on arriving
at their grey matter. The ascending branches are short, but
the descending extend some distance down the medulla, as a
special bundle, the funiculus solitarius, lying immediately
under the vago-glossopharyngeal nucleus. This bundle is
sometimes called the descending sensory root of the glosso-
pharyngeal, or, from its supposed importance for the respira-
tory centre, the respiratory bundle of Gierke.

THE EEAIN 623

The motor fibres of the vago-glossopharyngeal, \Yhich are
splanchnic in function, arise from a mass of grey matter lying
deeply in the medulla, and corresponding apparently to the
lateral horn. This nucleus is known as the nucleus amhiguus
{n.am., Fig. 282).

At the upper part of the medulla, where the fourth ven-
tricle attains its greatest diameter, the important eighth
nerve enters (Fig. 295, p. 639). This really consists of two
nerves, an outer division derived from the cochlea and
carrying auditory sensations, and an inner division derived
from the vestibule and semicircular canals and convej'ing
afferent impressions wdiich determine the maintenance of
equilibrium. These nerves are purely sensory, and are
•derived from Inpolar cells situated in the internal ear. As
they enter the medulla they are separated by the mass of
white fibres forming the restiform body. Both sets of fibres
bifurcate on entering the medulla. The branches of the
cochlear nerve make connection with two collections of cells,
the dorsal nucleus, apparently embedded in the fibres of the
root itself, and the accessory nucleus, a little triangular
mass of grey matter situated in the angle between the
cochlear and vestibular nerves. From these nuclei fibres
are given off which take two courses. Some, following the
previous course of the cochlear nerve, pass across the sur-
face of the fourth ventricle as the stricB meduUares or stricB
acousticce, and then bending inwards pass into the tegmentum
of the opposite side. Others pass deeply and form a mass of
transverse fibres in the ventral part of the tegmentum, known
as the corpus trapezoides. After making connections with
the superior olivary body and a special nucleus, they join the
superficial set of fibres, and pass up in the tegmentum to the
inferior corpora quadrigemina, forming the lateral fillet.

The vestihular nerve also has two nuclei of termination,
the median nucleus with small cells, and the lateral or
Deiters' nucleus with large cells. The descending fibres end
chiefl}' in the median nucleus, wdiile the ascending fibres end
in Deiters' nucleus. From the latter a distinct band of fibres
passes up to the cerebellum, forming the median division of
the restiform body, while other fibres run across to the teg-
mentum of the opposite side, wdiere they take part in the
formation of ihe posterior longitudinal bundle.

624 PHYSiOLoaY

In a section tlirough tlie fourih ventricle through the
middle of the pons, a group of large cells is seen in the
position occupied by the nucleus of the hypoglossal below.
In this situation however these cells give rise to the fibres
of the sixth nerve. Another group is seen lying laterally and
more deeply, evidently belonging to the lateral horn system.
This is the nucleus of the seventh or facial nerve, the fibres
of which pass dorsally and anteriorly, looping round the sixth
nerve-nucleus, before issuing as the root of the seventh nerve.

In the upper part of the pons we find the big fifth nerve
with its two roots. The fibres of the sensory root derived
from the cells of the Gasserian ganglion bifurcate. The
upper divisions, which are short, end in a mass of grey
matter at the lateral part of the formatio reticularis, the
so-called sensory root, while the descending divisions form a
long strand of white fibres passing down as far as the second
cervical nerve. They form a sort of cap to the siihstantia
gelatinosa of Rolando, around the small cells of which the
fibres finally terminate. The motor fibres arise partly from
the motor nucleus, a mass of cells lying internally to the
sensory nucleus and belonging probably to the lateral horn
system. A large number however are derived from a long
column of cells, which stretches forward from the nucleus
as far as the level of the anterior corpora quadrigemina.
These fibres are known as the descending motor root of the
fifth nerve.

In the regit)n of the mid-brain, besides the root of the
fifth nerve just mentioned, we find only the motor nuclei of
the fourth and third nerves, which are situated near the
median line in the ventral part of the central grey matter,
corresponding in situation to the sixth and twelfth nerves
lower down.

Intermediate Grey Matter of the Cerebral. Axis

The masses of grey matter which are found throughout
this region may be regarded as extra shunting stations (or
association centres for various systems of nuclei and conduct-
ing paths), which have arisen in consequence of the great
complexity of reaction required of the nerve mechanisms in
connection with the organs of special sense. We must

THE BRAIN 625

confine ourselves here to little more than the enumeration
of some of the chief masses, though we shall have occasion
to refer to some in more detail when dealing with the co-
ordinating mechanisms of the cerebral axis. From below
upwards we may enumerate the following grey masses :

In the medulla is the large olivary body, with the accessory
olive lying on its inner side. Each olive sends fibres across
the middle line to the opposite cerebellar hemisphere, and
must be regarded as connected with this body in its functions,
since atrophy or removal of one side of the cerebellum is
followed by atrophy of the opposite olive.

In the pons we find a similar but smaller body, the
superior olive, in the neighbourhood of the nucleus of the
seventh nerve. The superior olive is closely connected with
the co-ordination of visual and vestibular impressions with
the eye movements (Fig. 290).

Deiters' nucleus, which occurs in the same region, although
described as one of the nuclei of the eighth nerve, might
equally well be included in this class owing to its manifold
connections with both afferent and efferent mechanisms.

In close connection with Deiters' nucleus are a number of
grey masses in the cerebellum, the so-called roof-nuclei in
the roof of the fourth ventricle, and the dentate nucleus in
the middle of each cerebellar hemisphere.

In the mid -brain we must mention the superficial grey
matter covering the corpora quadrigemina.

On the ventral side of the Sylvian iter are various masses
of grey matter in the crura, the red nucleus, a large mass in
the tegmentum just below the oculo-motor nucleus, and the
substantia nigra, which divides each crus into two parts, the
dorsal tegmentum and the ventral pes or crusta.

Finally at the fore part of the cerebral axis we come to
the two great ganglionic masses already described, the optic
thalamus and the corpus striatum. The optic thalamus is
connected by fibres with all parts of the cortex and represents
the termination of the whole tegmental system, so that in
many ways it may be regarded as a sort of foreman of the
central nervous system, bringing all parts of this system in
relation with the supreme cerebral cortex.

The corpus striatum on the other hand represents the

40

626

PHYSIOLOGY

most primitive part of the cerebral hemispheres. It does
not act as the intermediary between the cortex and the lower
parts of the brain, but its fibres run to lower levels in company
with those from the cortex. It seems possible that it may
under conditions carry out in a simple way the functions which,
with more elaboration, need the co-operation of the cortex.

Face

Diagrammatic vertical section through brain showing course of
pyramidal fibres. M.C. Cortex on which are situated the motor
centres. I.C. Internal capsule. C.N. Caudate nucleus. O.T.
Optic thalamus. L.N. Lenticular nucleus. D. Point of decus-
sation of fibres to F.N., facial nucleus. VII. Seventh nerve.
P. Pyramids of medulla. A.P. Anterior pyramidal tract.
Lp. Lateral pyramidal tract. M.O. Medulla oblongata. S.C.
Spinal cord. Cbl. Cerebellum.

The Comiecting Tracts of the Brain

The tracts of the white matter of the brain may be divided
into the longitudinal tracts which connect different levels of
the brain with one another, and the commissural or transverse

THE BRAIN

627

tracts which run across from one side of the brain to the
other and serve to connect the two sides of the brain at the
same level. The longitudinal tracts may be divided into
those contained in the crusta or pes and its continuations,
and those which run in the tegmentum.

The Pedal System. — The most important of these tracts is
the ijyramidal tract of fibres which, arising from cells in the
central portion of the cerebral cortex (the motor area), pass
along the corona radiata and converge to form the genu and
anterior two-thirds of the posterior limb of the internal

Fig. 287.

Horizontal section through basal ganglion to show arrangement
of fibres in internal capsule. From before backwards the fibres
go to the motor centres for the eye, head, tongue, mouth,
shoulder, elbow, fingers, abdomen, hip, knee, and foot. S. Fibres
from temporo-occipital region, oc. Fibres to occipital lobe.
op. Optic radiations. Nc. Nucleus caudatus. O.T. Optic thala-
mus. N.L. Nucleus lenticularis. (After Sherrington.)

capsule. The arrangement of fibres in the mternal capsule
according to their function is indicated in Fig. 287. Thence
they pass through the crura cerebri, takmg up the middle
two-thirds of the crusta, and then through the pons.
Emerging from the lower border of the pons, they form two
thick masses, the anterior pj^amids of the medulla. At the
lower part of the medulla, the major portion of the fibres
passes across to the posterior part of the lateral column of the
other side, and is continued down this side as the crossed
pyramidal tract. A small number of fibres of each tract do
not cross at once, but pass down in the cord in the same
situation as they occupied in the medulla, forming the direct

628 PHYSIOLOGY

or anterior pyramidal tracts. These however also cross
gradually in the cord before reaching their final destination —
the anterior cornu of the opposite side.

The anterior limb of the internal capsule in front of the
genu is occupied by the frontal cortical fibres, which are
derived from the grey matter of the frontal lobes and which
proceed along the innermost portion of the crusta to the
pons, where they end, probably in indirect connection with the
transverse fibres of the middle peduncle of the cerebellum.

Immediately behind the pyramidal tracts in the posterior
limb of the internal capsule is a collection of fibres (the

Fio. 288.

Transverse section through mid-brain to show position of
fillet and pyramid. A.Q. Anterior corpus quadrigeminum.
dV. Descending root of fifth nerve. F. Fillet (I, lateral,
and m, mesial fillet). Pyr. Pyramid. Fr. Fibres from
frontal lobe to pons. T.O. Fibres from occipital lobe
to pons. Ne. P'ibres from nucleus caudatus to pons.
III. Pioot of third nerve. S. Sylvian iter. Kn. Red nucleus.

te7nporo-occi2yital cortical) which run from the temporo-
occipital convolutions of the cortex through the internal
capsule and along the outer lateral border of the crusta to
end in the pons in the same manner as the frontal fibres just
described.

A fourth constituent of the crusta, which does not appear
in the internal capsule, is the small band of fibres derived
from the caudate nucleus of the corpus striatum. These
firbes seem to end partly in the substantia nigra itself and
partly, along with the others of this system, in the pons
Varolii.

The Tegmental System. — Whereas the pedal system con-
sists of fibres which for the most part degenerate downwards

Fig. 289.

Cortex cerebri

Lateral fillet -

Post' columns'^--, _

Corpora quadrigemma
Sup- cerebellar peduncle
Sup- vermis

Restiform body
Cracile & cuneate nuclei

--Ant • cerebellar tract

--Post' cerebellar tract

Diagram to show possible paths of afferent impulses from posterior
roots to cerebral cortex. The fillet path is represented in black,
the cerebellar path in red.

THE BRAIN 631

and, in the case of the pyramidal tracts at any rate, carry
efferent impulses, the tegmentum furnishes the various
alternative paths for afferent impulses on their way to the
cerebral hemispheres.

Two main courses are open for these impulses (Fig. 289).
They may travel (1) by the dorsal column nuclei and tract
of the fillet or (2) indirectly through the intermediation of
the cerebellum.

1. The fillet path. — The posterior nerve-roots send direct
contmuations into the posterior columns of the cord. The
fibres m these columns end by arborisations round the
cells of the gracile and cuneate nuclei. From these cells
fresh relays arise which cross as the internal arcuate fibres
•to the inter-olivary layer on the other side of the medulla in
the supra-pyramidal or sensory decussation. Hence they pass
up in the tegmental region of the pons and in the tegmentum
of the crus as a flat band of fibres — the fillet, which divides
into two portions known as the lateral and median divisionSc
The lateral fillet is formed almost entirely by fibres from the
cochlear nucleus and ends in the corpora quadrigemina. The
median division, which receives also accessions from the sen-
sory nuclei of the bulb, ends partly in the grey matter of the
anterior corpus quadrigeminum, the great majority of the
fibres however passing to the thalamus itself. From the
thalamus fibres proceed to the frontal and parietal cortex
through the extreme anterior end of the internal capsule,
while others pass through the posterior third of the hind limb
to be distributed to all parts of the temporal and occipital
lobes. The latter fibres, which are associated with others
derived from the anterior corpus quadrigeminum and concerned
largely with the passage of visual impulses, are often spoken
of as the optic radiations.

2. The cerebellar path. — The posterior roots, as they
enter the cord, send collaterals to arborise round the cells of
Clarke's column and other cells of the grey matter. From
these cells fibres arise which form the anterior and posterior
cerebellar tracts. The anterior (antero-lateral ascending)
tract passes up in the lateral columns through the pons into
the superior peduncle of the cerebellum, where it loops round
to end in the superior vermis. The posterior (direct) cere-
bellar tract also passes up into the superior vermis of the

632

PHYSIOLOGY

cerebellum by the restiform body. By the same path the
cerebellum also receives fibres from the gracile and cuneate
nuclei of both sides.

The continuation forwards of these impulses is by means
of the superior cerebellar peduncles, which, arising chiefly in
the dentate and roof nuclei but also to a certain extent in
the superficial grey matter of the cerebellum, pass forwards

Fig. 290.

Ant. Corp. quad.

Optic tract.

Sup.oliv

Sup. olive.
Post. longitudinal bundle.

Diagram to illustrate some of the connections of the nuclei of
the nerves to the ocular muscles (after Held).

to the corpora quadrigemina. Converging below these bodies
they decussate, and finally end in the tegmentum, chiefly in
connection with the red nucleus. The further continuation
to the cerebral hemispheres must lie in the tracts already
described connecting them with the tegmentum.

The posterior lo7igitiidinal bundle (Fig. 290) is a distinct
tract of white fibres lying dorsally to the reticular formation.
In front it runs just below the oculo-motor nucleus, with which

THE BRAIN 633

it is connected, and can be traced backwards (or downwards) as
far as the first cervical nerve, where it merges in the ground
fibres (anterior basis bundle) of the anterior columns. It is
made up partly of descending fibres from the anterior corpus
quadrigeminum and nuclei of the floor of the third ventricle,
partly of ascending fibres from the various sensory nuclei of the
medulla. One of its chief functions is to serve as a means of
communication between the various oculo-motor nuclei (third,
fourth, and sixth nerves) around the cells of which many of
its fibres end.

The Commissural Fibres of the Central Nervous System

The chief mass of these is contained in the corpus callo-
sum which connects the two opposite cerebral hemispheres.

Other smaller commissures are the anterior white com-
missure connecting chiefly the olfactory lobes and temporo-
sphenoidal convolutions, and the posterior commissure between
the two thalami.

The great mass of transverse fibres forming the pons,
which serve to connect the cerebellar hemispheres, are not
directly continuous across the middle line but, starting from
the superficial grey matter of one hemisphere, end in the grey
matter of the opposite side of the pons.

634 PHYSIOLOGY

Section 2

SUMMAEY OF THE CONNECTIONS AND FUNCTIONS
OF THE CEANIAL NEEVES

Cranial nerves. — The cranial nerves are generally reckoned
as twelve in number : 1st, olfactory ; 2nd, optic ; 3rd, oculo-
motor; 4th, or trochlear; 5th, or trigeminus; 6th; 7th, or
facial ; 8th, auditory ; 9th, glossopharyngeal ; 10th, vagus or
pneumogastric ; 11th, spinal accessory ; 12th, hypoglossal.

Of these the first two stand on a different footing from
the rest which, like the spinal nerves, are outgrowths of
nerve-fibres from the central tube of grey matter surrounding
the neural canal or from ganglia corresponding to the spinal
posterior root-ganglion. The olfactory and optic nerves are
not peripheral nerves at all, but are actual outgrowths from
the brain. The olfactory bulb and the retina are morpho-
logically distinct lobes of the brain.

The first or olfactory nerve (or, more properly, olfactory
lobe) has ten or twelve filaments, which pierce the cribriform
plate, and are distributed to the olfactory mucous membrane.
It is the central organ of smell. It is supposed that impulses
do not cross from one side of the body to the cerebral hemi-
sphere of the opposite side, as is the case with all the other
nerves of the body.

The second or optic nerve subserves the function of vision,
and that alone. The two nerves join at the optic cliiasma.
Here there is a partial exchange of fibres, and each of the
optic tracts, which are the continuations behind the chiasma
of the optic nerves, contains fibres from both optic nerves.

Thus the right optic tract contains the fibres from the
external half of the right retma and the internal half of the
left retina. Since these are corresponding parts of the two
retinae, and are excited by light commg from the left of the
person, section of one optic tract causes, blindness on the
opposite side (hemianopia) . Each optic tract is connected
behind with the back part of the optic thalamus (pulvmar),
the external corpus geniculatum, and the anterior corpus
quadrigeminum of the same side (Fig. 291). From these

THE BRAIN

635

points fibres pass through the posterior part of the internal
capsule and corona radiata {'optic radiations ') to the cortex
of the occipital lobe.

The fibres forming the optic tracts are the axons of the
nerve-cells in the ganglion-cell layer of the retina. Section
of the optic nerve therefore is followed by degeneration of
these fibres in a central direction. Mixed up with these fibres

Fig. 291.

Diagram to show connections of optic tracts (after Sherrington).
L, left, and K, right retina. OD. Optic decussation (chiasma).
OpT. Optic tract. NO. Nucleus caudatus. LN. Lenticular
nucleus. Th. Optic thalamus. G. External geniculate body.
AQ. Anterior corpus quadrigeminum. P. Pulvinar. OpE.
Optic radiations running to 0 C, the occipital cortex. Ill.n.
Nucleus of 3rd nerve in tloor of Sylvian aqueduct. IV. Fourth
ventricle.

however are others which run in a centrifugal direction, start-
ing from cells in the optic thalamus or adjacent masses of
grey matter and terminating in the inner nuclear layer of the
retina (Fig. 292).

The third or oculo-motor nerve arises from a column of
nerve-cells situated at the extreme hind part of the floor of the
third ventricle, and from the front part of the floor of the

636

PHYSIOLOGY

aqueduct of Sylvius, below the anterior corpus quadrigeminum.
It emerges from the inner side of the crus cerebri. It is the
motor nerve for the levator palpebrarum, superior, inferior,
and internal recti, and inferior oblique muscles. It also
supplies the constrictor iridis and the ciliary muscle. Stimu-
lation of it therefore causes the eye to look upwards and
inwards, with contraction of the pupil and spasm of accommo-
dation. By careful stimulation of various parts of its nucleus
the different movements of these muscles may be produced
separately.

The nucleus of the fourth nerve is situated just behind
that for the third in the floor of the Sylvian aqueduct. The

Fi(i. 292.

Schema of the course of the visual impulse from rods and cones to
brain (Bechterew after Ramon y Cajal). A, retina ; B, optic nerve ;
C, external geniculate body, a, cone ; b, rods ; c, d, bi-polar cells ;
e, ganglion cells ; /, centrifugal fibre ; g, spongioblast ; h, terminal
ramifications of retinal nerve-fibres ; j, cells transmitting impulse
to cortex ; T, cell giving off centrifugal fibres.

fibres run from here round the aqueduct, and take their super-
ficial origin from the valve of Vieussens, a thin plate of grey
matter forming the roof of the fourth ventricle just in front
of the cerebellum.

This nerve supplies only the superior oblique muscle of
the eyeball.

The fiftli or trigeminus resembles a spinal nerve in that it
has a motor as well as a sensory root, the latter being provided
with a ganglion (Gasserian ganglion). It has a very extensive
origin, owing to the fact that its sensory part represents the
sensory roots of all the motor cranial nerves from the third

THE BRAIN

637

to the hypoglossal. The middle or motor root arises from a
collection of nerve -cells in the floor of the fourth ventricle.
It also receives fibres from the descending motor root, which
can be traced forwards from the nucleus as far as the level of
the anterior corpora quadrigemina.

The sensory root may also be traced mto a nucleus lying
lateral to the motor nucleus, though in this case the fibres of
the nerve end in the nucleus, having their trophic centre in
the cells of the Gasserian ganglion. Connected with the
sensory nucleus is the descending root of the fifth nerve, which
can be traced downwards through the medulla as far as the

Fm. 293.

Corpora qn.-idri-
getnlna

Eminentia teres

Strife acousticaj
Ala cinerea

Calamus scriptoriiis

Xucleiis of iii
Xncleus of iv

Motor nncleiis of v
.sensory niicleu?; of v
Nucleus of vi
Xucleus of facial
Principal nucleus of

auditory
Nucleus of glosso-

pharyiigeal
Nucleus of vagus

Nucleus of spinal
accessory

Nucleus of hypo-
glossal

Diagram of fourth ventricle and adjacent parts, as seen from dorsal
aspect, to show positions of nerve nuclei. These are marked on the
right-hand half. (After Erb.)

level of the second cervical nerve, where it appears as a little
cap of white fibres on the mass of gelatinous substance forming
the head of the posterior horn, and known in the medulla as
the tubercle of Eolando.

This nerve is the motor nerve for the muscles of mastica-
tion, and for the tensor tympani and tensor palati. It is the
sensory nerve for the whole of the face (including eyeball,
mouth, and nose). It also contains dilator fibres to blood-
vessels derived from the chorda tympani, and is said to have
trophic functions. The latter conclusion is from the fact that
section of the fifth nerve in the skull is followed by ulceration
and sloughing of the cornea, and finally destructive changes

638

PHYSIOLOGY

involving the whole eyeball. Since however these results may
be prevented by carefully shielding the eye from all dust and
deleterious influences, it is probable that the ulceration is
merely a secondary consequence of the anaesthesia. The
cornea being anaesthetic, foreign objects that fall on its surface
are allowed to remain there, and so give rise to injurious
changes and ulceration.

The fifth is also said to be the nerve of taste for the
anterior third of the tongue, but it is possible that the taste -
fibres which run in the fifth are derived from the glosso-
pharyngeal.

Fig. 294.

Uoot-flbres of v

Superior olive

Root-fibres of facial

Root-fibres of vi
Olivary body

Pyramidal tract

Motor nucleus of V

Sensory nucleus of v
Nucleus of vi
Genu of facial
Nucleus of facial
Strife acousticiB
Nucleus of auditory
Nucleus of glosso-
pharyngeal
Nucleus of vagus
Nucleus of spinal

accessory
Nucleus of hypo-
glossal

Diagram to show positions of principal nerve nuclei in pons and
medulla, side view. The organ is supposed to be split down the
middle line and the right half viewed from the mesial side.
The most mesially situated nuclei are shaded, the others stippled.
(After Erb.)

The sixth nerve, the motor nerve for the external rectus,
rises from a small group of cells in the floor of the fourth
ventricle near the middle line.

The nucleus for the facial or seventh nerve is situated
more deeply and laterally than the preceding. It supplies
all the muscles of the face, and is therefore the nerve of
expression.

The chorda tympani, which is a branch of this nerve,
contains secretory and vaso-dilator fibres for the submaxillary
gland. The fibres of taste which are said to run in this nerve
are probably derived from the glosso-pharyngeal.

The eighth or auditory rises on a level with the hind

THE BKAIN 639

margin of the pons by two roots, one of which, the dorsal
root, winds round the restiform body, while the other, the
ventral or median root, sinks into the substance of the bulb
to the inner side of the restiform body. The fibres composing
the dorsal roots come from the cochlea and convey sensations
of sound. The fibres bifurcate, the ascending branches ending
in the dorsal nucleus (acoustic tubercle), while the descending
make connection vvith a mass of cells in the angle between the
two roots, known as the accessory nucleus. The ventral root
consists of fibres derived from the vestibule and semicircular
canals, and carries impulses connected with the reflex main-
tenance of equilibrium. It ends partly in the lateral auditory

Fig. 295.
Cbni

Section through medulla just behind the pons?, to show origin of
anditoiy neive. Cbm. Cerebellum. V. Fourth ventricle. E. Resti-
form body. Py. Pyramid. Va. Ascending root of fifth nerve.
VII. Nucleus of seventh nerve. VIII. Auditory nerve.

nucleus (of Deiters), whence a number of fibres pass up with
the restiform body into the cerebellum, and partly in the
median nucleus.

The ninth, tenth, and eleventh nerves are connected with
an elongated nucleus in the lateral part of the lower half of
the fourth ventricle, the motor fibres of the first two nerves
arising from the nucleus ambiguus.

The ninth is probably a pure sensory nerve, and conveys
sensations from tongue (taste?) and pharynx. Eunning in
it are also motor fibres to the stylo-pharyngeus and middle
constrictor of the pharynx.

The tenth or vagus is joined by the accessory part of the
spinal accessory, so that the two nerves may be considered

640 PHYSIOLOGY

together. It has both afferent and efferent functions, most of
which we have already considered.

Efferent functions :

Motor to levator palati and three constrictors of

pharynx.
Motor to muscles of larynx.
Inhibitory to heart.
Motor to muscular walls of oesophagus, stomach, and

small intestine.
Motor to unstriated muscle in walls of bronchi and

bronchioles.
Secretory to glands of stomach and possibly to pancreas.

Afferent functions :

Eegulate respiration. Stimulation of central end may
quicken respiration and promote inspiration, or may
inhibit inspiration. Stimulation of central end of
superior laryngeal causes stoppage of inspiration,
expiration, cough.

Depressor (from heart to vaso-motor centre).

Reflex inhibition of heart.

The external branch of the spinal accessory is the motor
nerve of the sterno-mastoid and trapezius muscles.

The hyjjoglossal {twelfth, nerve) arises from a nucleus in
the floor of the fourth ventricle at its lower end close to the
middle line.

It is a pure motor nerve, and supplies the intrinsic and
extrinsic muscles of the tongue.

Since the integrity of the nuclei of the cranial nerves is a
necessary condition for the carrying out of various reflex acts
in which these nerves are involved, the grey matter of the
fourth ventricle and aqueduct is often spoken of as if it were
cut up into a series of centres distinct for every act. It must
be remembered however that, when a dozen or more centres
are enumerated as being situated in the fourth ventricle, it is
not meant that we can anatomically distinguish a group of
cells for each act or group of actions named. When we say
that a part of the nervous system is a centre for any action,
we merely mean that this part forms a necessary link, or

THE BRAIN 641

meeting of the ways, in the complicated directing of nerve
impulses that takes place in every co-ordinated act.

The chief centres are the respiratory and the vaso-motor.
These we have already considered. Other centres that may
be enumerated are —

Centres for movements of intrinsic and extrinsic ocular
muscles.

Cardiac inhibition.

Mastication, deglutition.

Sucking.

Convulsive (connected with respiratory).

Vomiting.

Diabetic (connected with vaso-motor, v. p. 492).

Salivary.

Centres of phonation and articulation.

41

642 PHYSIOLOGY

Section 3
FUNCTIONS OF THE CEREBRAL AXIS

We have already studied the phenomena exhihited by an
animal (frog) possessing spinal cord alone. We can now by
a study of the same or a higher animal, deprived only of its
cerebral hemispheres, come to some conclusion concerning
the functions of the lower parts of the brain and, by com-
parison of these phenomena with those exhibited by an intact
animal, of the cerebral hemispheres themselves.

When a frog's cerebral hemispheres have been excised, a
casual observer would not at first notice anything abnormal
about the animal. He sits up in his usual position, and on
stimulation may be made to jump away, guiding himself by
sight, so that he avoids any obstacles in his path. Move-
ments of swallowing and breathing are normally carried out.
The animal, thrown on to his back, immediately turns over
again. If put into water, he swims about until he comes to
a floating piece of wood or any support, when he crawls out
of the water and sits still. If he be placed on a board and
the board be inclined, he begins to crawl slowly up it, and by
gradually increasing its inclination he may be made to crawl
up one side and down the other. But a striking difference
between him and a normal frog is the almost entire absence
of spontaneous motion — that is to say, motion not reflexly
provoked by changes immediately taking place in his environ-
ment. All psychical phenomena seem to be absent. He feels
no hunger and shows no fear, and will suffer a fly to crawl
over his nose without snapping at it. ' In a word, he is an
extremely complex machine, whose actions, so far as they go,
tend to self-preservation ; but still a machine in this sense,
that it seems to contain no incalculable element. By applying
the right sensory stimulus to him, we are almost as certain of
getting a fixed response as an organist is when he pulls out a
certain stoj).' ^

The effects of ablation of the cerebral hemispheres of the
pigeon are very similar. If left to itself, the bird remains

' James, ' PsycboloKy.'

THE BRAIN 643

perfectly still and seems fast asleep ; if stimulated, it may be
made to fly normally, and is then observed to avoid obstacles,
guided by the sense of sight. Like the frog, it shows no
signs of fear or hunger, and will starve to death on a heap
of corn, although it will begin to eat the corn if its beak
be plunged into it. In the higher mammals ablation of the
cerebral hemispheres produces such severe shock that nothing
can be said with regard to the working of the lower part of
the brain. The rabbit however will survive the operation for
a few hours, and during this time it can be made to run, and
no symptoms of paralysis are observed. When a sensory
surface or nerve is stimulated, the animal gives forth a
prolonged and plaintive cry. We thus see that the axial
■parts of the brain, together with the corpora quadrigemina
and cerebellum, contain all the necessary nervous mechanisms
for the carrying out of the co-ordinated muscular actions
involved in standing, running, flying, mastication, deglutition,
and expression of the emotions.

Co-ordination of Muscular Actions

The first two of these functions must be considered a little
more fully. The maintenance of equilibrium depends on a
series of complex reflex acts, which are dependent on incoming
or afferent impulses, on various centres or interlacements of
nerve-paths in the grey matter, and on efferent impulses to
the muscles.

The chief afferent impulses which guide the maintenance
of equilibrium are those from the skin, eyes, semicircular
canals, and muscles themselves. The importance of impulses
from the skin is shown by those cases in which, from disease
of the sensory tracts, there is anaesthesia of the soles of the
feet. In these cases the patient is unable to stand with
his eyes shut, and indeed may first discover that anything
is wrong with him from the fact that he is apt to fall down
whenever he is washing his face. The same effect may
be experimentally produced by freezing the soles of the feet,
so as to make them ans'sthetic. If in a brainless frog the
skin be stripped from the hind limbs, it no longer sits up
in a normal posture, and is unable to climb up an inclined
board.

644 PHYSIOLOGY

The use of visual impulses in guiding the nervous centres
in the maintenance of equilibrium is shown by the preceding
experiment, in which no loss of equilibrium occurred till the
patient closed his eyes. Sudden destruction of the eye in
pigeons or rabbits causes these animals to spin round and
round in a circle, or may cause them to fall over. The
giddiness too, that is often produced by looking at rapidly
moving objects, such as a train or waterfall, shows the con-
nection of this sense with equilibration.

By far the most important afferent impulses are those
coming from the semicircular canals. A full account of the
effects of interference with these structures has been already
given in the chapter on the organs of special sense, where
too the intimate connections of the semicircular canals with
the movements of the eyes and head have been described.

Finally, all the muscular actions required for the main-
tenance of equilibrium are guided and regulated by afferent
impulses from the muscles themselves. The muscular sense
however is still more important in the co-ordination of the
muscular contractions by which locomotion is carried out.
This is well exemplified in certain cases where, owing to
disease of the intra-muscular afferent nerves, or of the sensory
channels of the cord, there is a loss of muscular sense accom-
panied by loss of muscular tone and tendon reflexes. Such
cases are said to suffer from ataxy. There is no propor-
tionality between the contractions of the various muscles
used, so that some muscles act too strongly and others too
feebly. In this way a vast amount of energy is expended
with very little practical effect in moving the patient along.

It is difficult to say that the function of co-ordinating
movements or maintaining equilibrium is limited to any dis-
tinct part of the cerebro-spinal axis. We have already seen
that all the machinery necessary for carrying out some of the
most complicated movements of locomotion is present in the
spinal cord ; and it is probable that under normal circum-
stances all that the higher centres do is to set this machinery
going. We may say that these functions are served by the
whole cerebro-spinal axis from the tliird ventricle to the
lower end of the spinal cord, together with the outgrowths
forming the corpora quadrigemina and the cerebellum.
There is a good deal of evidence connecting the latter organ

THE BRAIN 645

more closely with the co-ordination of movements than with
any other function. We may therefore take this opportunity
of considering the chief points in the structure and connec-
tions of this organ, as well as some suhsidiary co-ordinating
mechanisms in close connection with the cerehellum.

Cerebellum

Structure. — As we have already seen, the cerebellum is
formed by an outgrowth from tlie dorsal wall of the anterior
part of the fourth ventricle, and consists of a superficial
layer of grey matter enclosmg white matter. It is divided
into three lobes, two lateral lobes, and one middle lobe
forming the superior and inferior vermis. The surface of
the' cerebellum is increased by being thrown into leaf-like
folds, so that a section of this organ has a tree-like appear-
ance. A section through a lamina shows three distinct zones
— an outer molecular presenting a granular appearance with
a few nuclei ; internal to this, a granular layer composed of
many nuclei of nerve-cells ; and most deeply a central core of
white matter. Between the molecular and granular layers
are situated the cells of Purkinje, large flask-shaped cells
each with one apical dendrite, distinguished above all other
dendrites of the central nervous system by the richness of
its l)ranching, and with one axon, which leaves the base of
the cell and passes down into the central white matter, giving
off collaterals in its course.

In preparations made l)y Golgi's method we are able to
distinguish the various elements composing these layers
and their relations. The molecular layer, besides neuroglia
cells and the branching dendrites of the cells of Purkmje,
cojitains certain star-shaped cells (a. Fig. 296), which give off
an axon running parallel with the surface in the molecular
layer. From this axon branches dip down towards the cells
of Purkinje, where they end in a rich basket-work of fibres
around the body and beginning of the axon of these cells.
The nuclear layer presents two kinds of cells. The most
numerous is a small cell with a few short dendrites, each of
which terminates in a claw-shaped arborisation, and a single
long axon, which passes straight up into the molecular layer,
where it bifurcates, forming two branches which run parallel

646

PHYSIOLOGY

with the surface m a direction at right angles to the plane of
expansion of the dendrites of Purkinje's cells, apparently
resting against the serrations on the edges of these processes.
The second kind of cell in the granular layer is the so-
called Golgi's cell — a large cell with many dendrites and
an axon which terminates by frequent branches in the neigh-
bouring grey matter.

Fig. 296.

Molecular
layer.

Cells of
Puikinje

Schema of constituent elements of cerebellum (modified from Bolim
and Davidoff). On the left is a section of the cortex as it appears
when stained by ordinary methods. The middle portion represents
diagrammatically a section at right angles to the laminse, while to
the right of the dotted line the section is taken in the same plane as
the laminte. a, star-shaped cells of molecular layer ; b, b, cells of
Purkinje ; c, ' Golgi cell ' ; d, small cells of nuclear layer ; e, ' tendril
fibre ' ; f , ' moss fibre ' ; g, axon of cell of Purkinje.

The fibres making up the white matter are of three
kinds — two afferent and one efferent. The moss fibres, so
called from the curious thickenmgs they present in the
nuclear layer, pass up into the grey matter and terminate
by frequent branches in this layer. The tendril fibres,
also afferent, end in a rich arborisation which surrounds the
distal part of the cell and the bases of the dendrites of the

THE BEAIN 647

cells of Purkinje. The efferent fibres are represented by
the axons of the cells of Purkinje, which acquire a medullary
sheath and run down into the white matter.

This slight sketcli of the anatomy gives us a conception
of the extreme complexity of choice presented to nervous
impulses traversing the cerebellar cortex. Thus a discharge
along an axon of the cell of Purkinje ma}'^ be excited (1) by
an impulse ascending the tendril fibres, or (2) by one
ascending the moss fibres through the granule cells, and
then passing by their bifurcating axon to the dendrites of
the cells of Purkinje, or (3) by the star-shaped cells of the
molecular layer and their basket-work round the body of
Purkinje's cells.

Conuectionfi of the Gerehdlnm. — Although these have been
already touched upon in dealing with the brain as a whole,
they may be summarised here in order to guide us in the
discussion of the cerebellar functions.

By the Inferior j^fduncles afferent fibres pass to superior
vermis —

1. From Clarke's column of the same side by the posterior
cerebellar tract.

2. From both sets of dorsal nuclei, and therefore in-
directly from the posterior columns and posterior spinal
roots of both sides.

3. By the internal restiform body (C.V.T., Figs. 297 and
298) from the vestibular division of the eighth nerve, part of
the fibres passing through Deiters' nucleus.

By the middle jjediincles fibres pass to the other side of
the pons, where they enter into relation with the frontal
cortical and temporo-occipital fibres, which pass from the
cerebral cortex of the opposite side by the lateral portions
of the crusta to end in this region.

By the superior peduncles the dentate nucleus of the cere-
bellum, and to a certain extent the cortex, are connected
with the red nucleus and thalamus of the opposite side.
Moreover the fibres of the antero-lateral ascending tract
enter the cerebellum by this peduncle and terminate in the
superior vermis.

It will be observed that, ji.dging from the direction of
degeneration, most of these tracts, so far as the cerebellum
is concerned, are chiefly afferent. No direct connection of

648

PHYSIOLOGY

tlie cerebellum with the nuclei of motor nerves has been
described, but there is a very important indirect connection
by means of the so-called auditory nucleus or nucleus of
Deiters. The connections of this nucleus are shown in
Fig. 298. Receiving fibres from the roof-nuclei of the cere-
})ellum, as w^ell as directly from the semicircular canals by
the vestibular nerve, it gives off a number of efferent fibres.
These may be divided into two classes. One set, the vesti-
bulo-spinal fibres, pass down the cord as the antero-lateral
descending tract, the fibres of which terminate in the anterior
cornu on the same side of the cord. The second set of

Fig. 297.

Sup. Vermis

r2p.

Sebeniatic representation of some of the connections of the
cerebellum (Bruce). C.E., inferior peduncle or restiform l)ody;
S.C.P., superior peduncle ; CD., corpus dentatum ; E.N., roof
nuclei ; S.F., sagittal fibres from cortex to roof nuclei ; C.V.T.,
cerebello- vestibular tract ; D.N., Deiters' nucleus ; VIII, vesti-
bular nerve.

fibres, passing inwards, terminate partly in the nucleus of the
sixth nerve and partly turn upwards and downwards in the
posterior longitudinal bundle, making connections with the
nuclei of the fourth and third nerves, while the descending
fibres run down in the anterior column and apparently end
in the anterior cornu.

Functions of the CereheUum. — We thus see that the cere-
bellum is connected directly with the sensory mechanisms
chiefly of the same side of the body, with the cortex of the
opposite cerebral hemisphere, and indirectly with the motor
mechanisms of the same side of the body, as well as of the

TEE BRAIN

649

eye muscles. It is moreover specially connected with the
semicircular canals. By its complexity and connections it
is therefore eminently fitted to take its part in controlling
and guiding all hodily movements, especially those of the same
side of the body. It is therefore surprising to find how

C.R.v

Fia. 298.

Sup.Vermls

Schema of connections of Deiters' nucleus (Bruce). C.R.,
restiform body; E.N., roof nuclei; S.F., sagittal fibres from
cortex to roof nuclei ; C.V.T., eerebello-vestibular tract ;
D.N., Deiters' nucleus; III, VI, nuclei of third and sixth
nerves ; P.L.F., posterior longitudinal bundle ; VIII, vesti-
bular division of eighth nerve ; S.C., semicircular canals ;
V.S.T., vestihulo-spinal fibres.

very slight relatively are the disturbances produced by
its complete ablation. In fact we learn more from experi-
ments in which only one half of the cerebellum has been
removed, as we are then able to compare the affected with
the relatively sound side. After such an operation there is
at first marked loss of co-ordinating power. The animal tends
to fall towards the side of the lesion, and we may get

(;50 PHYSIOLOGY

forced inovenients of the body or of the e.yes to the opposite
8ide. After some time these acute disturljances pass away,
and the only point to be noticed is a loss of power and of
tone in the muscles of the side of the body from which
the cerebellum has been removed. Complete or extensive
destruction of the cerebellum in man has a more evident
effect, owing to the greater co-ordinating capacity necessary
for maintaining the erect posture whilst standing and walk-
ing. In such cases we observe an inco-ordination of move-
ment exactly resembling that of a drunken man, and this
may at times be associated with nodding movements of the
head or forced lateral movements (nystagmus) of the eye-
balls.

It has been suggested that the chief action of the cere-
bellum is to exert a moderating restrahiing influence on the
cortex cerebri. But the facts mentioned above seem to show
that its action is rather to keep the motor mechanisms both
of the cortex and the spinal cord in a state of wakefulness,
ready to contract in co-ordinated sequence to peripheral
stimuli.

More important is tlie connection of the cerebellum with
the organs of static sense (the semicircular canals and the
otolith organs in the saccule and utricle). We have seen
that the spinal cord contains all the apparatus required for
the carrying out of co-ordinated movements, with their com-
plicated play of afferent and efferent impulses. Any such
movement requires —

(1) The appropriate peripheral stimulus, usually applied
to the skin, and, according to its character, exciting different
sets of nerve fibres.

(2) The centre or series of centres in the spinal cord.
The afferent impulse on arrival at the cord causes discharge
of motor impulses to certain muscles, and a central inhibition
of the tone of the antagonistic muscles.

(3) The adaptation of the extent of the contraction to the
original stimulus involves a secondary reflex, from muscle
through cord ; the afferent nerves of the muscle conveying to
the centres accurate information as to the strength of con-
traction of the muscle.

A movement therefore is started by a skin impression
involves reciprocal innervation (motor and inhibitory) of

THE BRAIN 651

antagonistic muscles, and these responses are in theiv turn
guided and controlled by afferent impulses excited by the
movements and arising chiefly in the muscles themselves. If
this apparatus is all in working order, why cannot an animal
stand or walk (except with great attention and training) after
the destruction of the cerebellum ? The answer is to be
found in the fact that every animal (quadruped or biped) is,
when erect, in a state of unstable equilibrium, the slightest
movement tending to displace the centre of gravity, so that the
animal would fall if the displacement were not at once reme-
died by muscular contractions. It is the special office of the
cerebellum to co-ordinate the movements (already co-ordinated
with one another by the spinal cord) with the position of the
body in relation to its centre of gravity. On this account
it receives impulses from the semicircular canals, from the
eyes, from skin, joints, and muscles, and sits, so to speak, on
the motor path from cortex to spinal cord, maintaining
continually a tonic hold on the muscles, which may be
strengthened or relaxed according to the position of the
animal.

The diagonal movements of the limbs in walking causes
an alternate shifting of the centre of gravity to one side or
the other. Each lateral movement would and does cause the
animal to fall, if the position be not immediately remedied by
the influence of the cerebellum.

After extirpation of the cerebellum in a dog, the animal
falls to one side or the other as soon as it tries to walk.
Later it learns to walk by an entirely new mode of progres-
sion, viz. a series of jumps, in which the hind limbs or fore
limbs move together, being sprawled widely apart, so as to
widen as much as possible the basis of support and avoid the
alternate lateral displacements of the centre of gravity inci-
dent on the normal method of locomotion.

E.^roTiONAL Expression

By appropriate stimuli it is possible to elicit in animals
deprived of their cerebral hemispheres the outward bodily
manifestations which we usually regard as the expressions
of certain emotions. Now an emotion is a psychical state,
or state of consciousness ; but it is dependent for its pro-

652 PHYSIOLOGY

duction on the existence of certain bodily changes— affections
of the heart, vascular system, voluntary muscles — which are
involuntary and reflexly produced. The mechanism for this
reflex production is present in the lower cerebral centres, so
that severe stimulation of a sensory nerve in a hemisphere-
less rabbit causes it to utter a long, plaintive scream. The
brainless frog responds with a croak, almost indicative of
pleasure, each time its back is gently stroked. In neither
of these, nor in any similar cases, are we justified in speaking
as if an emotional state of consciousness were present, We
have no reason to think that the rabbit suffers pain, or that
the frog is pleased, in the two above-mentioned experiments,
but merely that certain changes in the bodily condition are
reflexly produced, which, if the cerebral hemispheres were
present, would be represented in consciousness as an emotion
of pain or pleasure.

When a patient is slightly under the influence of chloro-
form, it frequently happens that all the emotional expressions
are preserved, although consciousness is totally abolished ;
he may cry out or struggle when cut with the knife, and
yet when he recovers from the anaesthetic he will state that
he felt nothing whatever of the operation.

THE BEAIN 663

Section 4
CEREBEAL HEMISPHEEES

Structure of the Cerebral Cortex

We have considered the connections of the hemispheres
so fully in the previous sections that it remains now only to
describe shortly the chief points in their structure.

The cortex, as in the cerebellum, consists of a superficial
layer of grey matter covering a central mass of white fibres,
and, as in the cerebellum, increased area of surface with
growing intelligence is afforded by the folding of the surface
into, convolutions and fissures. The chief convolutions are
indicated in Figs. 301, 302.

On section the grey matter is seen to consist of many
layers of nerve-cells embedded in a mass of tissue composed of
neuroglia and many fine nerve-fibres, both medullated and
non-medullated. The nerve-cells vary in size and shape, but
one kind of cell is typical of this part of the nervous system.
This is the pyramidal cell (Fig. 299, g), and consists of
a cone-shaped cell-body with one large apical dendrite which
runs towards the surface and breaks up in the superficial
molecular layer into a number of branches. Dendrites also
pass oft" from the sides and lower angles of the cell. The
axon arising from the middle of the base of the cell passes
downwards into the white matter, giving oft" collaterals in its
course. Some of these, especially those from the large cells
of the ' motor ' area of the cortex, pass into the pyramidal
tracts.

Although not so distinctly stratified as the cerebellar
cortex, the cerebral grey matter can be divided into four
(or in some situations five) layers. Most superficial is the
molecular layer, composed of the dendrites of the pyramidal
cells, and certain spindle-shaped ' jjluripolar ' cells, i.e. cells
with several apparently nervous processes running parallel
to the surface. These are sometimes spoken of as ' associa-
tion cells.'

Next to this comes a layer of small pyramidal cells, which
is succeeded by a layer of small cells known as the granular

654

PHYSIOLOGY

Fig. 299.

UL

Diagrammatic section of cerebral cortex (from Barker, after Starr,
Strong, and Learning). L molecular layer with o, bipolar cell;
II, layer of small pyramidal cells; III, layer of large pyramidal
cells ; IV, polymorphous layer ; V, white matter.

THE BRAIN

655

layer. Below this, in the motor cortex, is a layer of large
pyramidal or Betz cells, while deepest of all is the 'poly-
morphous ' layer, composed of many types of cells, ordinary
pyramidal cells, pyramidal cells with the base and axon
tm-ned towards the surface (cells of Martinotti), and * Golgi
cells ' with a freely branching axon which terminates in the
adjacent grey matter. Among the nerve-fibres passing
between grey and white matter, four types (Fig. 300) can be
distinguished :

a. Projection fibres, passing from the pyramidal cells to
lower levels of the central nervous system. These include
the various fibres, pyramidal and otherwise, that make up
the internal capsule and the crusta.

Fiu. 300.

Schematic section through cerebral hemispheres, to show chief
classes of nerve tracts (after Eamon y Cajal). A, corpus cal-
losum ; B, anterior commissure ; C, pyramidal tract ; a, cell
giving off projection fibre ; b, cell giving oil' commissural fibre ;
f , cell with axon forming association fibres.

h. Commissural fibres passmg across the corpus callosum
and anterior commissure to the opposite hemisphere.

c. Association fibres passing from one part of the cortex
to another on the same side of the brain.

d. Afierent or sensory fibres, starting in most cases from
the region of the thalamus and passing up to termmate by
branching in the superficial layer of the cortex.

In a section through the cortex, stained by some method such as Weigert's,
to display medullated nerve-fibres, in addition to the bundles of radial fibres

656 PHYSIOLOGY

vimning from the white matter perpendicularly to the &urface, bands of
tangential fibres are seen running parallel to the surface in certain situations,
viz.: —

(a) A layer just under the surface of the cortex.

(b) A layer between the molecular and small pyramidal layer, the outer line
of Baillarger.

(c) A layer betsveen the granular and large pyramidal cell layers, the inner
line of Baillarger.

(d) In addition to these a special layer of tangential fibres is present in the
occipital lobe, running through the middle of the granular layer, and dividing
it into two. This is known as the line of Gennari.

Differences are observed in the structure of various parts of the cortex
corresponding to their functions. Thus we may say roughly that the small
pyramidal layer is chiefly associational in function, the large pyramidal cells
are motor, the granular layer is sensory, while the polymorphous layer
presides over the lowest cortical functions, such as the getting of food, the
sexual instincts, etc.

Thus, in a low animal, such as the rabbit, the polymorphous layer has three
times the thickness of the pyramidal layer, whereas in man, with his infinitely
greater ideational powers, it is only one-third the thickness of this layer.

In man, in an associational area such as the prefrontal convolutions, the
pyramidal layer is almost as thick as all the rest put together. In the visual
area (occipital lobes) the granular layer is the thickest, and is divided into two
layers by the band of tangential fibres forming the line of Gennari. In the
motor area (chieMy the descending frontal convolution), we find below the
granular layer, the well-marked large pyramidal cells, or Betz cells, though here
also the pyramidal cell layer is very thick. In this area the actual average
thicknesses of tlie different layers are as follows : —

Molecular 0-31 mm.

Small pyramidal 0-90 mm.

Granular 0-22 mm.

Betz layer 0-22 mm.

Polymorphous ..... 0'61 mm.

Functions of the Cortex
We may come to some conclusions as to the general
functions of the cerebral hemispheres if we compare the
behaviour of a normal animal with one that has been deprived
of its cerebral hemispheres. In the former case it is quite
impossible to foretell what particular reaction may be evoked
by any stimulus. It may produce the same effect as when
applied to a brainless animal, but in most cases the reaction
is modified in various ways. The animal is no longer a mere
machine that can be played on at will, but is an individual
whose actions are ruled by a guiding intelligence, who is
actuated by motives and by feelings of fear, hunger, pain, and
the like. In short, an animal, whose cerebral hemispheres
are intact, presents phenomena analogous to those which in

THE BEAIN

657

ourselves are associated with changes in the state of con-
sciousness, and which we call voUtion or feehng.

It was formerly thought that in all their functions the
cerebral hemispheres acted as an entity, and that any
voluntary movement or any change in the state of con-
sciousness might be considered as carried out by all parts
of the hemispheres acting together. It has long been known
however that each cerebral hemisphere innervates the
opposite side of the body. Thus if the cortex of one hemi-
sphere be destroyed or be functionally separated from the
lower parts of the brain by destruction of the internal
capsule, paralysis (hemiplegia) and loss of sensation on the

. . Fig. 301.

Motor centres on outer surface of monkey's brain.
(After Campbell and Sherrington.)

opposite side of the body are produced. The paralysis is
limited to voluntary, and may not affect reflex or emotional
movements. It is interesting to note that those movements,
which are usually carried out by the muscles on both sides
of the body at the same time, are not so affected, probably
in consequence of the close interdependence of the bulbar and
spinal centres for these movements, and partly because these
movements are equally represented in both hemispheres.

Moreover, during the last twenty years, conclusive evi-
dence has been brought forward of the localisation of func-
tion in the cerebral cortex of each side of the brain. This
evidence is physiological and pathological, but in both cases
it falls under the head of excitation, or of destruction and
consequent paralysis. On exciting certain parts of the

42

658

PHYSIOLOGY

cortex, situated in the neighbourhood of the fissure of
Rolando, definite co-ordinated movements of certain muscles
or groups of muscles are produced, varying in their distri-
bution according to the exact spot stimulated. Thus stimula-
tion with the faradic or galvanic current of the convolutions
at the upper part of the fissure of Rolando causes co-
ordinated movements of the lower limb ; of the middle part,
movements of the upper limb ; and of the lower part
(including the third frontal convolution), movements of the
head and face. In the higher apes and in man the motor
centres all lie in front of the fissure of Rolando.

These experiments are corroborated by others in which
definite parts of the Rolandic area of the cortex are destroyed.

Fig. 302.

Motor centres on mesial surface of monkey's brain
(After Campbell and Sherrington.)

Destruction of any given zone of the motor area produces
paralysis of voluntary movement in the part represented by
this portion of the cortex. Thus if, on stimulation of a spot
near the centre of the fissure of Rolando, we obtain a definite
movement of the arm of the opposite side, and we then excise
the cortex at this spot, we find that after the operation the
animal has lost voluntary power over this movement and over
none other.

It was formerly thought that the grey matter was not
directly excitable, and that the effects of electric stimuli were
due to excitation of the underlying fibres of the corona radiata.
The direct excitability of the grey matter is however proved
by the following considerations.

1. There is greater ' lost-time ' in the grey matter than in

THE BEAIN 659

the underlying white matter ; that is, if we first stimulate the
grey matter, and then shave this off and stimulate the white
matter below, it is found that the latent period, which elapses
between the time when the stimulus is sent in and the time at
which the contraction takes place, is far greater in the former
than in the latter case.

2. It is very common, as the result of excessive stimulation
of the cortex, to get, not a single contraction of the group of
muscles represented in the area stimulated, but an epileptic
convulsion, which starts in this group of muscles and spreads
thence to all the other muscles of the body. The convulsion
consists of two stages :

. (a) The tonic stage, in which all the muscles of the body
may be in a state of continued contraction.

'{!)) The clonic stage, which lasts a good deal longer than
the first stage, and consists of rapid rhythmical jerking move-
ments of the muscles. This is followed by —

(c) A stage of exhaustion, in which the cortex is relatively
inexcitable.

If the grey matter oh both sides be removed, stimulation
of the white fibres of the corona radiata does not produce a
typical epileptic fit.

Pathological evidence bears out the results on localisation
deduced from the physiological experiments just mentioned.
Thus we have cases in which a tumour pressing on a part of
the motor area causes twitching movements of the limb, or
more or less complete epileptic convulsions, starting in the
particular limb represented in the affected area of the cortex.
On the other hand, cases frequently occur in which parts of
the cortex are destroyed by pressure of a growing tumour,
or by stoppage of the vessels supplying that area, giving rise
to paralysis of definite muscles or groups of muscles.

After a movement has been abolished by extirpation of a
definite area of the cortex, a considerable amount of recovery
of movement may take place. The degree to which this may
occur varies in different classes of animals, being more com-
plete in the lower animals, such as the dog and rabbit, than
in the monkey and man. It probably depends on the taking
up of the functions of the extirpated area, partly by the ad-
joining regions of the cortex, and partly by the corresponding
centre of the opposite hemisphere, all the centres of the two

660 PHYSIOLOGY

sides of the brain being functionally connected by means of
the corpus callosum.

A point of considerable importance is the fact that move-
ments rather than muscles are cortically represented. Thus
stimulation of the right frontal lobes causes a movement
(conjugate deviation) of both eyes to the left. In this move-
ment the external rectus of the left side and the internal
rectus of the right side are both set in action by stimulation
of the right cortex. Similarly, we may produce movement
of the head to the left by stimulation of the proper spot of
the right cortex. In this movement the right sterno-mastoid
and the left external oblique muscles are involved.

When we speak of motor centres it must not be supposed
that motor impulses start de novo in the pyramidal cells of
these centres. Here, as in all other parts of the central
nervous system, the activity of the cells is excited exclusively
by impulses arriving at them from other parts, and ultimately
from the periphery of the body.

The absolute dependence of the activity of the pyramidal cells on afferent
stimuli is well shown by an experiment carried out by Mott and Sherrington.
These observers divided all the posterior roots of the brachial plexus in the
monkey, and found that the effect was to cause motor paralysis of all the finer
movements of the arm and hand. On exposing the corresponding area of the
cortex and exciting it electrically, all the missing movements could be induced,
showing that the cortical cells needed only the arrival of a stimulus to make
them discharge. No experiment could show better the ultimate reflex character
of those movements which are generally distinguished as voluntary or purposive.

These impulses, since they are afferent so far as the
pyramidal cell is concerned, may be spoken of as sensory,
and the collection of exalted reflex centres which make up
the Eolandic area may therefore be justly termed sensori-
motor. In fact, many obs3rvers believe that it is in the motor
area that the sensation of touch and pressure on the correspond-
ing limbs is perceived, and that the motor effect of exciting
this part of the cortex is normally produced as a reaction to
such touch or pressure sensations. Hence in extensive lesions
of the motor area sensation as well as movement may be
affected, and a certain amount of anaesthesia may accompany
the paralysis.

Sensory areas. — If in the monkey the right occipital lobe
be stimulated, there is movement of both eyes to the left.

THE BEAIN 661

This experiment by itself is capable of two interpretations :
either the occipital lobe is to be regarded as a motor centre
to the ocular muscles, or it is a sensory centre of sight, and
the animal looks towards the left because visual sensations
are aroused and referred to the left side of the field of vision.
The latter explanation is shown to be true by the effects of
extirpation. If the occipital cortex be destroyed, the animal
is rendered blind on the side opposite the lesion. It is said
to suffer from hemianopia (half -blindness). Excision of both
the occipital lobes causes total blindness. Since the rays of
the left half of the field of vision fall on the right-hand side
of the two retinae, and left hemianopia is produced by de-
struction of the right occipital lobe, the temporal half of the

Fig. 303.

Diagram showing functional connection of occipital lobes with the two
retime, c. Optic chiasma. o. Occipital lobes.

right retina and the nasal half of the left retina must be
innervated from the right occipital cortex (Fig. 303). The
connection, however, of the occipital lobe with the retina of
the other side is more complete than with the retina of the
same side, so that after destruction of the right lobe loss of
vision is more extensive in the left than in the right eye.

Our evidence as to the localisation of the other senses in
the cortex is less complete. The sense of hearing is located
by Ferrier in the superior temporo-sphenoidal lobe. Stimu-
lation of this part causes pricking of the ears ; destruction of
it produces different effects according to the experimenter ;
it may give rise to deafness on the opposite side (Ferrier),
or to no appreciable results (Schafer).

Clinical as well as anatomical observations however concur
in locating auditory sensations in this convolution. The fact
that after experimental extirpation the animal reacts to sounds
does not prove the absence of impairment of auditory sensa-

662

PHYSIOLOGY

tio)is, since the lower centres contain all the mechanism for
a simple motor reaction to an incident sound-wave.

Smell and taste have been localised in the caput cornu
Ammonis and the uncinate gyrus.

Fig. 304.

.«fi?s;S?^/i#*

Human Brain showing outer (A) and mesial (B) surfaces, and the
situation of the chief motor and sensory areas. The different
shading represents the extent of each of these areas as determined
by a study of the histological structure of the cortex. (Campbell.)

THE BEAIN 663

Many observers believe that general tactile sensibility as
well as muscular sensibility is cortically represented in the same
region as are muscular movements, i.e. in the Eolandic area.

From a study of the histological characters of the cerebral
cortex, Campbell has concluded that the chief seat of tactile
sensibility is to be found in the ascending parietal convolution,
behind the fissure of Eolando.

In an animal such as the dog, we are able in this way to
parcel out the greater part of the cerebral cortex into definite
motor and sensory areas. It is possible to difterentiate two
grades of representation of sensation in the so-called sensory
areas. The most primitive grade is concerned in the reception
of afferent impressions from definite sense-organs and in the
production of the appropriate cortical motor response. Sur-
roundmg or in immediate proximity to this area is generally
found a wider area, which may give no effect on electrical
stimulation, and is concerned in the * working up ' of the
primitive sense-impressions into the more complex condi-
tions, which we term ideas. The extent of these psychical
areas increases relatively to that of the sensory areas as we
ascend the animal scale. Thus in man the visuo-sensory area
occupies but a small portion of the cortex and is concerned
in the reception of simple visual sensations. Destruction of
this area on one side causes half -blindness, or hemianopia.
The greater part of the occipital lobe is taken up in the visuo-
psychic area, the whole of which is engaged in the combina-
tion of sensations from the eyes, so as to form the visual
ideas of things. Destruction of portions of this area will
not necessarily affect sight, but may affect more or less the
power of judging, through the medium of the eyes, of the
nature of things seen. The relative extent of the different
sensory and psycho-sensory areas of the human brain is repre-
sented in Fig. 304.

Aphasia. — If the cortex on the left side is destroyed,
power of speech is totally lost. The same effect is produced
if the lesion be limited to a small area in the third left
frontal convolution (Broca's convolution). Our normal right-
handedness is necessarily associated with and caused by the
activities of the left hemisphere predominating over and
guiding those of the right. In the movements that stand
highest in the evolution of the cerebral functions, those of

()64

PHYSIOLOGY

speech, the predommance of the left side is so marked that
destruction of the association centre for lips and tongue on
this side causes complete loss of the delicately co-ordinated
movements by which speech is produced.

Besides this motor aphasia, which is brought about by
a lesion of Broca's convolution, speech may be destroyed by

Fig. 305.

Diagram of cortical areas engaged in speech and writing (Eoss).
a. Broca's convolution (motor lip and tongue area), b. Arm
area. c. Auditory word-centre, d. Visual word-centre.

injury of the sensory psychical centres (sensory aphasia).
Thus in some cases in which the left superior temporo-
sphenoidal lobe was involved, there has been a condition of
word-deafness. The patient could not understand anything
that was said to him. He might be able to talk volubly, but
the words were mere gibberish ; his auditory word-centre being
absent, he was unable to appreciate the meaning of what he
was saying, and so the motor processes went on unchecked
by the criticism of sensory impressions. The talking of a

THE BRAIN 665

man with word-deafness may be compared to the walking of
a man with complete loss of muscular sense.

In the same way a lesion m the left occipital lobe may
cause loss of power to read (alexia) from blotting out of all
the higher visual memories, and more especially those con-
nected with written and printed words.

Any of these lesions may be attended with inability to
write, which in most people is intimately dependent on the
auditory and motor speech memories. Most people in writing
may be seen to move their lips slightly as they articulate
the words to themselves, thus showing that in writing the
arm-centre is acting in subordination to the mouth-speech
centre in the third left frontal convolution.

Fig. 305 represents simply the relationships of the various
centres on the left side to one another in speaking and
writing.

The most striking change, as we ascend the scale of in-
telligence in animals, in the structure of the brain is the
great development that occurs of brain-tissue, giving no
response on stimulation and presenting no immediate connec-
tion either with motion or sensation. Such tissue is found in
the pre-frontal and the parietal lobes, and in man forms the
greater part of the cerebral cortex. The fibres of these lobes
are found to acquire their myelin sheath a considerable time
after birth, and continuous development may go on as late as
the twentieth year. We are probably justified in ascribing
to these association-centres the chief part in the functions
of ideation and judgment. The ideas, which make up the
greater part of our mental life and which determine our
actions, cannot be regarded as essentially motor or sensory,
though in them motor and sensory processes of the present
are inextricably intermingled with the results of past sensory
and motor impressions ; and there is a constant war of mutual
excitations and inhibitions, the resultant of which is the
behaviour of the individual.

666 PHYSIOLOGY

Section 5

THE VASCULAK AND LYMPHATIC AEEANGEMENTS
OP THE CENTEAL NEEVOUS SYSTEM

The brain and spinal cord are enclosed in three mem-
branes, the dura mater, the arachnoid membrane, and the
pia mater.

The dura mater is a tough tibrous membrane, closely
adherent in the skull to the cranial bones, of which it forms
the periosteum, but in the spmal canal only loosely connected
with the vertebrae.

The pia mater is a finely fibrillated connective tissue,
closely adherent to the surface of both brain and spinal
cord, and sending prolongations into all the fissures of these
organs. It serves to convey the nutrient vessels to the
nervous tissue.

The space between dura mater and pia mater is divided
into two by a delicate membrane, the arachnoid. Both
arachnoid and dura mater send processes along the issuing
nerve-roots. The subdural and subarachnoid spaces are
both lined with endothelial cells. Although anatomically
separate, fluid can find its way with extreme ease from one
space to the other, so that physiologically they may be re-
garded as if in communication. The subarachnoid space is
put into connection with the ventricles of the brain and
central canal of the cord by means of a small opening m the
ependyma forming the roof of the fourth ventricle, which is
known as the foramen of Magendie.

On incising the dura mater through the atlanto-occipital
membrane, or in the spinal canal, a clear fluid wells up at
the bottom of the wound, and a continuous flow of this fluid
may with certam precautions be obtained by inserting a
cannula into the subdural space in either of these situations.
This liquid is the cerehro- spinal fluid. It consists of little
more than a solution of the salts of the blood -plasma, and
contains only the merest trace of proteid. This fluid appears
to be formed in the ventricles of the brain by a process
of secretion or transudation, modified by the cells of the

THE BRAIN 667

eiiendyma covering the vascular fringes, which project into"
the ventricles from the velum interpositum and are known as
the choroid plexuses. A slow formation of fluid is probably
always going on. Any excess of fluid that is formed may
either escape from the sheath of the dura mater along the
issuing nerve-roots or, when the pressure of the fluid is
higher than that in the venous sinuses, it may leave the
cranial cavity by a direct filtration through the walls of
these sinuses.

The lymphatic arrangements of the brain are still imper-
fectly understood. In the cortex cerebri the lymphatics are
perivascular, i.e. form complete tubes round the blood capil-
laries. These perivascular lymphatics are said to be in com-
munication with the subarachnoid cavity. If this is the
case, the lymph must mix with the cerebro-spinal fluid ; and
it would seem difficult to account for the small percentage
of proteid in this fluid — a percentage which seems quite
inadequate for the nutritional needs of the nervous tissues.

The Intracranial Circulation

The brain is supplied with blood from the two vertebral
and two internal carotid arteries, which anastomose at the
base of the brain to form the circle of Willis. On account
of this free anastomosis, one or two of these vessels can be
obliterated without any effect on the circulation ; and in the
dog, all four arteries can be ligatured without producing
more than a temporary lowering of the functions of the
cortex cerebri. The cortex is supplied by the posterior
cerebral from the basilar artery, and the middle and anterior
cerebral arteries from the internal carotid. Although the area
of distribution of these vessels does not coincide with the
functional areas of the cortex, it is important to remember
that blocking of the posterior cerebral artery will shut off the
blood from the occipital lobe, so causing softening of this
lobe and hemianopia ; while blocking of the middle cerebral
artery will affect the greater part of the Rolandic area,
with widespread paralysis on the opposite side of the body,
and probably some impairment of sensation, as its results.
If the lesion be on the left side, complete aphasia will be
produced. The symptoms of obstruction of the anterior

668 PHYSIOLOGY

cerebral artery will be less definite, since this vessel supplies
only a small portion of the Kolandic area, together with the
frontal lobes.

The optic thalamus and corpus striatum with the adjacent
parts are supplied by small vessels which come off directly
from the circle of Willis.

The veins of the brain pour their contents into a number
of venous sinuses in the substance of the dura mater. The
superior longitudinal sinus passes from before backwards
along the vertex of the cranium at the top of the falx cerebri
to the occiput, where it joins the straight sinus in the blood-
cavity known as the torcular Herophili. The straight sinus
carries the blood from the deeper parts of the brain, which
have arrived at it by the veins of Galen along the velum
interpositum. From the torcular the blood is carried by the
lateral sinus on each side to the internal jugular veins.

The circulation in the brain differs from that in all other
parts of the body, in that the cranial cavity forms a closed
cavity with rigid walls. A small amount of space may be
obtained in this cavity by the escape of cerebro- spinal fluid,
but beyond this change, which can amount only to one or two
c.c, we must say that the cubic contents of the cavity are
invariable. Hence, the brain-substance being incompressible,
dilatation of any one set of vessels can be obtained only at
the expense of the constriction of another set of vessels.
Thus a rise of arterial blood-pressure will cause a constriction
of the veins until the pressure in these vessels rises to the
pressure of the brain against them. Thus, as Leonard Hill
has pointed out, with rise of arterial pressure the circulatory
system of the brain tends to assimilate itself to a scheme of
rigid tubes, and the whole energy of the arterial pressure is
spent in maintaining an increased velocity of blood-flow.

The intracranial pressure is the same as the cerebral
capillary and venous pressures. In the dog in the horizontal
position it amounts to about 100 mm. H.^0, but it may vary
according to the position and circulatory conditions of the
animal within very wide limits without affecting the functions
of the brain.

Although the cerebral vessels are supplied with nerve-
fibres, we have as yet no definite experimental evidence of
vaso-motor changes in these vessels. Since the vascular

THE BRAIN 669

system of the whole body is under the control of a portion
of the brain, viz. the vaso-motor centre, the circulation
through the brain can be increased or diminished according
to its supreme needs by alterations of the circulation in other
parts of the body. Thus in the upright position, an adequate
pressure is maintained in the cerebral arteries by constriction
of vessels in the splanchnic area. The brain in fact uses
this great vascular area as the means for regulating its own
blood-s apply.

670

CHAPTER XVI
THE VISCERAL OR AUTONOMIC SYSTEM OF NERVES

We have already dealt with the chief functions of this system
of nerves in connection with the various organs of the body.
It remains only to consider some general points affecting the
anatomy and functions of this system as a whole.

The visceral, autonomic, or splanchnic system of nerves
includes the sympathetic system properly so called, and some
of the cranial and sacral nerves.

The sympathetic system (Fig. 306) is composed of a chain
of ganglia lying each side of the vertebral column, there
being as a rule one ganglion to each spinal nerve-root. In
the cervical region however these ganglia are condensed into
two, the superior and inferior cervical ganglia, united by the
cervical sympathetic trmik ; and the upper three or four tho-
racic ganglia on each side are condensed to form the so-called
stellate ganglion. At the bottom of the chain there is only
one coccygeal ganglion for the coccygeal vertebrae.

In the abdomen is a second system of ganglia, in especial
connection with the abdominal viscera, lying in front of the
aorta and surrounding the origins of the large arteries to the
alimentary canal. These are the semilunar or solar ganglia,
the superior mesenteric and the inferior mesenteric ganglia.

Finally in the organs themselves we find a third system
of ganglion cells either scattered or collected to form small
ganglia. These are probably connected not only with the
sympathetic but also with the other splanchnic nerves, cranial
and sacral. The three systems of ganglia have been distin-
guished as the lateral, collateral, and terminal ganglia.

The ganglia of the sympathetic chain are connected with
all the spinal nerves, just after they have given off their pos-
terior division by means of the rami communicantes. These
rami communicantes are of two kinds, white rami consisting

Pig. 306.

Sup.cerv

Inf. cerv

Stellate g.^

S^mp. chain

Semilunar g.^
Sup.mes.g.^,

C.I
2
3
4
5
6

>Arm i

3 > Head & Neck

>Arm

12
13

L.I
2

"i

4

leg

Abdominal
Viscera

> Leg < 5

S.I

2
3

Hypogastric n ^,^,y,,,_,_ '

Diagrammatic representation of the distribution of the sympathetic system.
The black lines represent the medullated preganglionic fibres, such as those
making up the white rami communicantes, while the post-ganglionic fibres
are printed in red. On the extreme right of the figure is indicated the
general distribution of the white rami arising from the several nerve-roots,
while the double brackets point to the nerve-roots making up the limb
plexuses. H, heart; S, stomach; 1, small intestine ; C, colon; B, bladder.

THE VISCEEAL OE AUTONOMIC SYSTEM OF NEEVES 673

of small medullated fibres, and grey rami composed almost
exclusively of non-medullated nerves.

It has been shown by Gaskell that the white rami are
formed by fibres which have their origin in the spinal cord
and perhaps in the posterior root ganglia ; whereas the grey
rami represent fibres which, arising in the sympathetic ganglia,
run back to join the spinal nerves. The visceral outflow
represented by the white rami is limited to a distinct region
of the cord, viz. from the first thoracic to the third or fourth
lumbar nerve-roots ; whereas the grey rami pass from the
sympathetic to all the spinal nerve-roots. It is found by
experiment however that stimulation of a limited number of
white rami produces all the effects that can be evoked by
stimulation of the grey rami, showing that the impulses
leaving the cord pass upwards and downwards in the sym-
pathetic system and are broken somewhere in their course,
being transferred to a fresh system which, by means of non-
medullated nerves, carries them on to their destination.

The relationships of the white and grey rami are strikingly
illustrated in the case of the pilomotor system of nerves.
These in the cat arise from the cord by the anterior roots
from the fourth thoracic to the third lumbar inclusive.
Passing by the white rami to the sympathetic system, they
travel upwards and downwards and end by arborisations in
the various ganglia of the main chain. From the cells of each
ganglion a fresh relay of fibres starts, which runs as a bundle
of non-medullated nerves (the grey ramus) to the correspond-
ing spinal nerve, with which it is distributed to its peripheral
destination. The position of the cells in the nerve-path can
be easily ascertained by the nicotine method described on
p. 265. Each grey ramus causes erection of the hairs above
one vertebra, whereas stimulation of one white ramus causes
erection over three or four vertebrae, showing a distribution
of the fibres of the white ramus to the cells in several succes-
sive ganglia.

We may summarise here the distribution of these pilo-
motor fibres in the cat.

1. For the head and upper part of the neck the fibres
arise by the fourth to the seventh thoracic anterior roots,
and have their cell-stations in the superior cervical ganglion.
They travel as small medullated nerve-fibres from the white

43

674 PHYSIOLOGY

rami up the sympathetic chain, through the stellate ganglion
and ansa Vieussenii and up the cervical sympathetic.

2. The next set of nerve-fibres have their cell-station in
the stellate ganglion. The white rami arise from the fifth to
the eighth thoracic nerves, while the grey rami pass to the
nerve-roots from the third cervical nerve to the fourth thoracic
nerve.

3. The remaining nerves supplying all the rest of the
body and tail arise by the white rami from the seventh
thoracic to the third or fourth lumbar nerve, and are distri-
buted as grey rami to all the spinal nerves below the fourth
thoracic.

We thus see that, in speaking of the functions of a spinal
nerve-root, we must clearly distinguish whether we mean the
root as it rises from the spinal cord, in which case its visceral
functions will include those of its white ramus, or whether
we mean the made-up or complete spinal nerve after it has
received its grey ramus (Fig. 307). In this latter case the
visceral functions of the root will be more restricted than m
the former case, and will have a different distribution. In
stimulating the nerve-roots in the spinal canal it is some-
times possible, by weak stimuli, to display the functions of
the corresponding white ramus, and then by increasing the
stimulus to get superadded the efl'ects due to excitation of
the grey ramus in the made-up nerve, in consequence of the
spread of current.

' When for example the eleventh thoracic anterior roots are stimulated in
the spinal canal with weak shocks, a fairly long strip of hairs in the lumbar
region will be erected, the maximum movement of the hairs being near the
middle of the strip. This marks the area of distribution of the pilomotor
nerves given by the eleventh thoracic nerve to the sympathetic. If then the
strength of the shocks be increased to a certain point, the hairs in the long
strip will of course be erected as before, but in addition there will be energetic
erection of hairs in a short strip a little distance above the long strip, and
separated from it by a quiescent region. This short strip is the same as that
affected by stimulating the grey ramus or the dorsal cutaneous branch of the
eleventh thoracic nerve. It marks the area of distribution of the pilomotor
fibres received by the spinal nerve from the sympathetic ' (Langley).

We may now indicate briefly the mam course and functions
of the fibres of the sympathetic system (Fig. 306) :

1. The head and neck are supplied by fibres leaving the
spinal cord by the first five dorsal nerves (chiefly by the

Fig. 307.

Posc'root-.
Ant" root

4- — Pre-ganglionic fibre

: — Symp. gangl.

Made-up" spinal nerve

^ Post-ganglionic fibre

Diagram (after Langley) to show the manner in which a spinal nerve is
completed by the entry of a grey ramus, containing fibres derived from
cells in the sympathetic chain, p.pr.d, posterior primary division.
(The post-ganglionic fibres are represented red.)

THE VISCERAL OR AUTONOMIC SYSTEM OF NERVES 677

second and third). They all have their cell-station in the
superior cervical ganglion. They convey :

Vaso-constrictor impulses to the blood-vessels.

Dilator fibres to the pupil.

Secretory (trophic?) fibres to the salivary glands and

sweat glands.
Vaso-dilator fibres to the lower lip (in the dog).

2. The thoracic viscera (heart and lungs) are supplied
by the same five nerve-roots. The cell-station of these
fibres is however situated in the stellate ganglion. They
convey :

Accelerator or augmentor impulses to the heart.
■ Vaso-constrictor impulses to the pulmonary blood-
vessels (?).

3. The abdominal viscera receive fibres from the lower
six dorsal nerves and the upper three or four lumbar. Most
of these fibres run through the sympathetic chain without
making any connection with the ganglia, and have their cell-
stations m the collateral ganglia of the solar plexus, the
semilunar and superior mesenteric ganglia. On their way
to these ganglia they form the greater and lesser splanchnic
nerves. Their functions are :

Vaso-constrictor for stomach and small intestine, kidney,

and spleen.
Probably vaso-dilator for the same viscera.
Inhibitory for both muscular coats of small intestine.
Motor for ileo-colic sphincter.
Secretory for pancreas (?).

4. The pelvic viscera are supplied by the lower dorsal
and upper three or four lumbar nerve-roots. These fibres
also pass by the main chain to make connections with the
cells chiefly in the mferior mesenteric ganglia. They
convey :

Vaso-constrictor impulses to pelvic viscera.

Inhibitory fibres to colon (both coats).

Motor and possibly also inhibitory fibres to bladder.

Motor fibres to retractor penis.

Motor fibres to uterus and vagina.

678 PHYSIOLOGY

5. The fore-limb receives nerves from the white rami of
the fom'th to the tenth thoracic nerves. All these fibres are
connected with cells in the stellate ganglion. They convey :

Vaso-constrictor impulses to blood-vessels.
Secretory nerves to the sweat-glands.

6. The hind limb is supplied by the nerve-roots from the
eleventh thoracic to the third lumbar inclusive. The cell-
stations of these fibres are situated in the sixth and seventh
lumbar and first sacral ganglia. They convey :

Vaso-constrictor impulses.
Secretory nerves to the sweat-glands.

Every fibre of the sympathetic system is thus in some
point of its course interrupted by a nerve-cell, and Langley
has shown that this is the only cell-break m the fibre, i.e.
every fibre is connected with one cell and one cell only.
This law applies not only to the sympathetic fibres, but also
to the fibres of the other visceral nerves. Each fibre there-
fore can be regarded as made up of two sections — a pre-
ganglionic fibre arismg in the central nervous system and
passing down to a ganglion as a fine medullated nerve-fibre,
and a post-ganglionic fibre arising in this ganglion and con-
tinued generally as a non-medullated fibre to its peripheral
distribution.

The efferent nerves of the sympathetic system arise in the
cells of the lateral horn, and thus are homologous with the
splanchnic fibres which arise in the medulla, viz. the motor
root of the fifth, the facial nerve, and the motor root of the
vago-glossopharyngeal.

According to Gaskell, the typical segmental nerve would have four roots :
two somatic, the motor and sensory roots distributed to the skin and skeletal
muscles ; and two splanchnic roots, also motor and sensory, composed of small
fibres and distributed to the viscera or structures which are visceral in origin,
e.g. developed from branchial arches.

In the spinal cord we have the proved separate origin of the motor fibres
from the anterior horn and the visceral efferent fibres from the lateral horn ;
and a similar distinction may be made in the medulla between such somatic
roots as the third, fourth, sixth, and twelfth nerves, and the splanchnic roots
represented by the motor root of the fifth, the facial nerve, and the motor root
of the vago-glossopharyngeal.

In the medulla a distinction can be drawn between the central connections
of the sijlanchnic afferent and the somatic afferent nerves. Examples of the
former are the vago-glossopharyngeal nucleus and the sensory nucleus of the

THE VISCERAL OE AUTONOMIC SYSTEM OF NERVES 679

fifth, and of the latter the long descending root of the fifth in connection with
the substance of Rolando. It is not known however whether a similar distinc-
tion can be drawn in the cord between the two sets of fibres.

Such of the visceral nerves as do not belong to the sympa-
thetic system arise chiefly in the medulla and in the sacral
region of the cord. Like those of sympathetic origin they
all conform to Langley's law as to the possession of one and
only one cell-station in their peripheral course. In most
cases these cells lie near the periphery, and belong therefore
to the terminal set of ganglia. The position of their nerve-
cells is as follows :

Third nerve. — The branches to the iris and ciliary muscle
are connected with cells in the ciliary ganglion.

Chorda tymjjcmi. — The vaso-dilator and secretory fibres
of this nerve are connected with cells lying near the glands ;
those to the sublingual gland with cells in the sublingual
(' submaxillary ') ganglion ; and those to the submaxillary
gland with scattered cells lying in the hilum of the gland.

Vagus. — The inhibitory nerves to the heart are connected
with ganglia in this organ itself. The motor fibres to the
oesophagus and stomach have their cell-stations in the
ganglion trunci vagi (in the alligator).

Pelvic visceral nerve. — This nerve is connected with a
collection of ganglia lying in the hypogastric plexus at the
base of the bladder. It has the following functions :

Dilator to vessels of the penis (hence its name of nervus
erigens) .

Dilator to vessels of pelvic viscera.
Motor to bladder, colon, and rectum.
Inhibitory to retractor penis.

It will be observed that in many cases the viscera get
their nerve-supply from both sets of visceral nerves, and
that in such cases the two sets of nerves are antagonistic in
function. It is impossible however to draw a sharp line
between the functions of the two sets, since the same nerve
may be motor for one set of muscular fibres and inhibitory
for another set in the same viscus. Thus the colonic branches
of the inferior mesenteric ganglion are motor (constrictor)
for the blood-vessels and inhibitory for the muscular walls of
the colon.

680 PHYSIOLOGY

Functions of the Sympathetic and Periphet'al Ganglia

These ganglia consist of a mass of nerve-cells embedded
in connective tissue, each cell being surrounded by a special
capsule of endothelial cells. The nerve-cells, though in
section resembling those in a posterior root ganglion, differ
from these in being multipolar, each cell probably possessing
one axon and several dendrites. The dendrites end in little
arborisations round adjacent cells.

Since the main nervous system is characterised by the
possession of nerve-cells, it was formerly thought that any
collection of nerve-cells must partake of the co-ordinating
and reflex functions of the central nervous system, i.e. must
act as local nervous centres. All efforts have failed how-
ever to prove the existence of such a function, and we must
conclude that the sole use of these ganglia is to serve as dis-
tributing centres. We may assume that one preganglionic
fibre divides, and the branches arborise round several cells
(Fig. 308), whence new fibres arise to carry the impulse
to the periphery — an impulse in the case of which there is
no need for any minute localisation. Indeed the essential
part of a nerve-centre is not the nerve- cells at all, but the
presence of a complex tangle of fibres, rendering possible
the passage of impulses in all directions, the passage of an
individual impulse however being limited by reason of the
varying strength of the impulse, and the varying resistance
of the many possible tracts. In many invertebrata the
nervous system consists of a punctated material composed of
a dense interlacement of fibrils, while the cells lie outside
the centres, and have one thick process dipping into the
nervous mass, from which process both axon and dendrites
arise. In this case it has been found that extirpation of the
cell-bodies does not destroy the capacity of the remaining
fibrillated substance to act as a reflex centre.

Such a complex of fibres is found in mammals in the
plexuses of Auerbach and Meissner which, as we have seen,
act as local nerve-centres for the intestine. But all such
mechanism is wanting in the sympathetic ganglia, which
contain neither association fibres between diflerent cells of a
ganglion nor commissural fibres between the cells of adjacent

Fig. 308.

-Spinal cord

:^Y\') Sympathetic chain

Solar ganglion

A.

B.

Figure (after Langley) to show the probable mode of connection
of the fibres of the splanchnic nerve with nerve-cells. A, usual
type, all the fibres passing through the lateral chain to end in
the collateral ganglia of the solar plexus ; B, alternative con-
dition, in which a small minority of the fibres have their cell-
stations in the sympathetic chain. The preganglionic fibres
are black, the post-ganglionic red.

THE YISCEEAL OE AUTONOMIC SYSTEM OF NERVES 683

ganglia. All the fibres in a sympathetic ganglion have either
entered it from the white rami or are destined to leave it as
fibres of grey rami.

Several reflexes formerly described in peripheral ganglia,
as e.g. the ' submaxillary ' ganglion, have been proved to be
fallacious. There is however a certain group of phenomena
which can be elicited in sympathetic ganglia, and which
have been termed by Langley and Anderson pseudo-reflexes,
or better, axon rejiexes. If for mstance we divide all the
nerves going to the inferior mesenteric ganglion, leaving the

Fki. 309.

Sp cord

Inf. mes-q.--i/^y-: ^
Post -ganglionic fibre -

Pre -ganglionic fibre
Hypogastric nerves

Diagram to illustrate Langley aud Anderson's explanation of
the lijiDogastric reflex as an axon reflex. The division of the
axon where the propagation or ' reflexion ' takes place is at X.

bladder connected with the inferior mesenteric ganglion only
by the hypogastric nerves, and then after dividing the left
nerve stimulate its central end, we obtain a contraction of
the right half of the bladder. This effect is abolished by
painting the inferior mesenteric ganglion with nicotine, show-
ing that the activity of the cells of this ganglion is involved
in the process. It has been shown however by Langley and
Anderson that this is not a true reflex, but is rather analogous
to Kiihne's gracilis experiment (cf. p. 163). A preganglionic
fibre arriving at the inferior mesenteric ganglion branches,

684 PHYSIOLOaY

one branch ending round the cells of the ganglion while the
other branch passes down in the left hypogastric nerve to a
cell situated near the base of the bladder (Fig. 309). When
therefore we stimulate this nerve we are stimulating a pre-
ganglionic fibre, and the excitation spreads up to the point
of junction of the two branches and then down the other
branch to excite the cell in the inferior mesenteric ganglion.
We thus obtain an apparent motor reflex by stimulation of
a nerve which is itself motor.

Similar pseudo-reflexes can be obtained along the abdo-
minal chain on the pilomotor nerves, but furnish no grounds
for ascribing the property of reflex centres to peripheral
ganglia.

685

CHAPTEE XVII
REPRODUCTION

Theoughout the animal kingdom we find the welfare of
the individual subordinated to that of the species. The
crowning act of an animal's life is the production of a new
individual, fitted in all respects to take the place of the
parent organism, and so to maintain the race on the earth.
In the case of the lowliest unicellular organisms, which
reproduce themselves only by fission, we cannot rightly
speak of death from natural causes. One amoeba divides
into two new individuals similar to it in every way, and
these in their turn divide again. Hence the amoebae have
with some right been spoken of as immortal. It is evident
that any accommodation of the organism to its environment
must, since it aflects the whole cell, be transmitted in equal
degree to the cells that are the offspring of the division of
the parent. And so we may, in course of time, get a gradual
change of type in the organism.

As we go higher in the scale we meet with more highly
differentiated organisms, consisting of cell colonies, each
member of which has its own appointed task to fulfil ; and
here we find that the office of reproduction also is confined
to one cell or group of cells. The immortality of the amoeba
has been transmitted to this group of cells. From this point
onwards, in the scale of animal life, we may regard the
reproductive cells or germ-plasma as being continuous through
successive generations. With the production of each new
generation the germ-plasma divides into two parts : one
part, the somatic half, forming what is generally miderstood
as the individual, and being differentiated into various forms
of cells to perform the multifarious functions of reaction
associated with life ; and the other half, persistent in its
primitive form as the reproductive part of the individual,

686 PHYSIOLOGY

ready when the time comes to divide again and give birth
to a new generation.

There are however many unicellular organisms in which
the processes of reproduction are not quite so simple.
These are able to multiply for a few generations by simple
fission. At the end of this time, for the production of
a new generation or series of generations, the conjoint action
of two cells is required. In this process of conjugation two
unicellular organisms come together and unite, their nuclei
fusing to form one nucleus ; the single cell thus made is
capable of producing by fission several more generations.
Here the cells that fuse are exactly alike in all respects.
A little higher in the scale however, among the multicellular
organisms, we find that the cells, which conjugate to form
a new cell capable of developing into an individual, present
somewhat different characters. The one cell, which has
generally a certain amount of stored-up reserve material in
its protoplasm, is the female element, and is called the ovum.
The other cell, which is chiefly limited to the nuclear sub-
stance, is called the spermatozoon, and is the male element.
This is the sexual mode of reproduction, which obtains in
all the higher animals.

The conjugation of these two cells is not the union of
the whole of two ordinary cells of two individuals. We
find that both ovum and spermatozoon, before their union,
undergo certain important changes, which have been more
fully studied in the case of the former. The nucleus of the
ovum just before fertilisation divides into two parts ; one
half is extruded with a small amount of the protoplasm, and
the other remains in the main body of the ovum. The
nucleus then undergoes division a second time, and again
one half is extruded with a little protoplasm. The two
extruded cells are spoken of as polar bodies, and do not
undergo any further modification. The part of the nucleus
left in the ovum is the female pronucleus. A similar change
takes place in the male element, and the nuclei of the
spermatozoa are equivalent to female pronuclei. These male
and female pronuclei have the power of uniting together to
form a whole nucleus, which is then capable of undergoing
a long series of divisions to form a new individual. The
union is effected by the penetration of the spermatozoon.

REPRODUCTION 687

which is in the higher animals mobile, into the ovum. Here
for a while two nuclei are seen, the male and female pro-
nuclei. They then fuse together, and the fertilised ovum is
now potentially a new individual, partaking of the charac-
teristics of both its parents.

Sexual life of man. — -The period of active sexual life,
during which the mdividual is capable of begetting or bear-
ing children, begins in both sexes at the age of fourteen to
sixteen, known as the age of puberty. In women, the
beginning of this period is marked by the onset of menstrua-
tion. This is the occurrence of a flow of mucus and blood,
which arises in the uterus, from the genital organs ; it lasts
from three to five days, and recurs regularly every four
weeks. Menstruation is associated with ovulation, which
consists in the discharge of an ovum from the ovary. This
latter contains follicles, each enclosing an ovum, which are
known as the Graafian follicles. They are lined with a layer
of cells — the membrana granulosa — which surround the ovum.
In the course of development these cells proliferate and
divide into two layers, each several cells thick, one of which
lines the follicle, and the other — discus proliger us — encloses
the ovum. The space between them is filled with colourless
fluid, which contains proteids. This fluid gradually mcreases
in amount until it forms a large projection on the surface of
the ovary. At or just before each menstrual period a ripe
Graafian follicle ruptures, and the ovum is discharged into
the fimbriated extremity of the Fallopian tube, down which
it is conducted to the uterus. This is accompanied with
congestion of the genital organs, especially of the uterus, in
consequence of which some of the smaller vessels of the
uterine mucous membrane rupture, and give rise to the dis-
charge of bloody fluid. The discharge of blood is accom-
panied with the fatty degeneration and disappearance of the
most superficial parts of the mucous membrane itself.

When the Graafian follicle ruptures, haemorrhage takes
place into its interior. This is followed by a rapid pro-
liferation of the cells of the membrana granulosa, which
grows in folds into the cavity, absorbing the blood- clot, and
transforming the haemoglobm into a yellow pigment. Hence
for some weeks after discharge of an ovum its Graafian
follicle may be recognised as a yellow spot which is known as

688 PHYSIOLOGY

the corpus luteurn. This is often spoken of as the spurious
corpus hiteum, to distinguish it from the corpus luteum of
pregnancy. If pregnancy does not follow the discharge of
the ovum, the corpus luteum disappears in from one to two
months. If however pregnancy occurs, the corpus luteum
becomes very large, forming a prominent projection on the
surface of the ovary, and is to be seen almost to the end of
pregnancy. Menstruation ceases during pregnancy, and is
also generally absent during lactation. It ceases altogether
between the ages of forty-five and fifty. After this time,
which is known as the climacteric, the woman is no longer
capable of bearing children.

Impregnation. — In animals which have a rutting season,
ovulation is also accompanied by a flow of blood from the
genital organs, and it is immediately after this period, which
corresponds to the menstrual period, that impregnation is
effected. In the human species impregnation may be effected
at any time, and the union of spermatozoa with the ova may
occur in the uterus. Fallopian tubes, or even in abnormal
cases on the surface of the ovary.

If the ovum be not fertilised, it is cast out with the blood
and products of disintegration of the uterine mucous mem-
brane at each menstrual period. If however it be fertilised
while in the Fallopian tube, a considerable thickening of the
uterine mucous membrane takes place from proliferation of
its cells, and it at the same time becomes very vascular.
When the ovum reaches the uterus it becomes embedded in
the mucous membrane covering the fundus of the uterus,
which grows round and completely encloses it. This
thickened mucous membrane, which is called the decidua,
becomes fused with the outer layer of the ovum, and the
latter, by means of its blood-vessels, derives its nourishment
from the uterine mucous membrane.

At about the eighth week after impregnation the forma-
tion of the j9Zace/?ifa. takes place in the following manner: —
A process of the internal hypoblastic layer of the embryo
grows out, carrying with it fcetal blood-vessels, and these
blood-vessels with their containing mesoblastic tissue extend
so as to completely surround the embryo. This outgrowth is
intimately applied to the decidua. At one spot it becomes
hypertrophied, and here sends in villi, covered with a single

EEPRODUCTION 689

layer of cells and supplied with blood-vessels ; these project
into maternal venous sinuses which have developed in the
thickened mucous membrane of the uterus.

Through the medium of this placenta the developing
animal obtains all the nutrient material it requires, both
oxygen and combustible foodstuffs. The vessels of the
fcetus are not in direct communication with those of the
mother. The interchange of material between the two must
be effected by the cells covering the placental villi, and
takes place in fact through two layers of cells, the endo-
thelium of the foetal vessels and the epithelium of the villi.
The placenta at the same time serves as an excretory organ

Fig. 310.

Diagram to show structure of human placenta, m.s. Maternal
venous sinus, v. Villus (outgrowth from chorion), containing
artery and vein with capillaries derived from the umbilical
vessels of the foetus, and covered with a single layer of epithelial
cells.

for the foetus, the effete material of the latter passing from
the capillaries to the blood in the venous sinuses which bathe
and surround the villi. The placenta is therefore alimentary,
respiratory, and excretory.

Parturition. — While the ovum is undergoing its wonderful
development, in which a complete human being is formed
out of a single cell by division and differentiation, the uterus
becomes very much enlarged, and its walls thickened by new
growth of unstriated muscular tissue. At the end of nine
months from the date of impregnation the development of the
foetus is complete, and parturition takes place. This consists
in the expulsion of the foetus by muscular contractions of
the uterus.

44

690 PHYSIOLOGY

Parturition or labour is divided into three stages. In the
first stage the contractions of the uterus, which are pamful
and are hence spoken of as ' pains,' are devoted to dilating
the OS uteri. This is effected by contractions of the longi-
tudinal muscles of the uterine wall, at the same time that the
foetus, contained in its bag of membranes, is forced against
and expands the os.

When the os is fully dilated the uterine contractions change
in character, becoming more prolonged, and are accompanied
by strong contractions of the abdominal muscles, which force
the child out through the vagina.

A short time after the birth of the child the pains recom-
mence, and expel the placenta with the decidua and the
foetal membranes. In this third stage the connection of the
uterine vessels with the placental sinuses is necessarily torn
through. Bleeding however is prevented by the fact that the
muscular fibres of the uterus remain firmly contracted after
birth, compressing and obliterating the lumen of the torn
vessels.

Directly the child is born, the uterus, contracting on the
placenta, compresses its vessels and prevents a further
supply of oxygen to the foetal vessels. The child therefore
becomes asphyxiated, and the venous blood, acting on the
medullary centres, calls forth the first act of respiration, and
the process is started which is to supply the needs of the new
individual with oxygen for the rest of its life.

Parturition is obviously a complex reflex act, and depends
for its normal carrying out on the integrity of the nervous
connections of the uterus with the spinal cord. The centre
for the act ot parturition lies in the lumbar spinal cord, and
it has been shown that parturition may go on normally in a
bitch whose cord has been completely divided in the dorsal
region. This act is then not necessarily dependent on the
co-activity of the voluntary centres.

After birth the enlarged uterus rapidly diminishes in size
in consequence of the atrophy and disintegration of the newly
formed muscular tissues, and this invohition is complete at
the end of three months.

Lactation. — ^The young child at birth is not independent,
but relies for many years for nourishment and protection
on the parents. For the first nine to twelve months of the

EEPEODUCTION 691

child s existence, under normal circumstances it is nourished
entirely on the secretion of the mammary glands of the mother.
The mammary glands vary largely in appearance according
to the condition of the woman from whom they are taken.
Before impregnation they are small, and on microscopical
examination are seen to consist of a number of branchmg
sinuous tubules, which are cut in various directions, and so
give the appearance of a number of alveoli. These tubules
are filled with a solid mass of epithelial cells. If impreg-
nation occurs, a marked hypertrophy of the gland takes
place, caused by the outgrowth of new columns of cells and
the formation of new tubules from the pre-existing ones.
At the same time the whole gland becomes more vascular
from the enlargement of the blood-vessels in the interstitial
connective tissue between the tubules. At the end of preg-
nancy the cells in the interior of the tubules undergo dis-
integration, leaving them lined with only a single layer of
cells. The active secretion of milk begins shortly before or
immediately after birth. The first milk that is secreted,
which is called the colostrimi, differs markedly from normal
milk as already described (p. 508). It contains less casein
and fat, but more albumen, than ordinary milk, and has in
addition a certain amount of globulin. Owmg to the large
amount of these last two bodies, colostrum coagulates on
boiling. Under the microscope, colostrum shows the pre-
sence of a number of cells with nuclei, or masses of proto-
plasm without nuclei (colostrum corpuscles) . Some of these
examined in fresh warm milk show amoeboid movements.
They probably have a twofold origin, from leucocytes which
have wandered into the lumen of the gland, and from central
cells of the tubules which have undergone disintegration.
The active secretion of ordmary milk sets m on the second
or third day after delivery. In the gland-cells we may dis-
tinguish a resting and an active condition, just as in the case
of other glands. In the acini of a resting gland the lumen
is wide and filled with milk, and the cells form a single flat
nucleated layer at the periphery. The inner margins of some
of the cells show jagged edges, and the protoplasm of all the
cells contains a few small granules. In an active gland, on
the other hand, the cells, which are long and columnar,
project far into the lumen. Many have two nuclei, and the

692

PHYSIOLOGY

central parts of all the cells are tilled with fat-granules and
finer granules, which are probably protein in character (cf.
Fig. 311).

The process which goes on in the transition from the
resting to the discharged condition is as follows. In some
of the cells, the central part, with its contained degenerated
daughter nucleus, breaks away entirely from the basal part,

Fig. 311.

Sections of mammary gland of guinea-pig (fat-granules stained
black with osniic acid).

A. During rest.

B. During active secretion. It will be noticed that in this case
the active formation of products of cell-metabolism (granules,
etc.) begins with the commencement of secretion, and does not
occur almost exclusively during rest, as in the salivary glands.
In the mammary gland, the active growth of protoplasm, the
formation of granules from the protoplasm, and the discharge
of these granules in the secretion, appear to go on at one and
the same time.

and in the lumen undergoes rapid disintegration, furnishing
to the fluid there protein, fat-globules, and probably sugar.
The change in the cells however need not be so radical as
this. Many simply discharge their fat-globules and their
other contents into the lumen. This discharge of cell-
contents is accompanied by a secretion of water and salts.
It must be remembered that in the secretion of milk its

REPEODUCTION 693

three chief constituents, caseinogen, lactose, and fat, are
manufactured by the cells of the mammary glands out of
the indifferent lymph which bathes them. This in its turn
is replenished from the blood circulating through the gland.
Caseinogen and milk-sugar are found nowhere else in the
body, nor in any other animal secretion. The fact that the
fat also is especially formed by the cells is shown by experi-
ments, in which a bitch was fed on pure protein food, and
excreted more fats in her milk than were contained in the
whole of her food. An increase in the fat in the milk is said
however to be brought about by an increased fatty diet, and
abnormal fats given in the food may appear among the fats of
the milk.

We see that the mammary gland in its mode of activity
holds a position midway between the submaxillary mucous
gland and the sebaceous glands of the skin. In the former
the cells manufacture a substance — mucigen — out of materials
brought to them by the blood, and this is discharged as mucin
when occasion requires, part of the protoplasm of the cells
always remaining intact, ready to build and store up mucigen
in its meshes. In the sebaceous gland the secretion is
furnished entirely by the disintegrated cells themselves, a
continual new formation of cells going on at the periphery of
the acini ; the older cells, as they are forced towards the
centre, undergo fatty degeneration, die, disintegrate, and are
cast out as the fatty material known as sehum on the surface
of the skin and at the roots of the hair.

The further rearing of the child, its maintenance and
education to fit it to become a useful member of society (that
is, one fit to continue the race on the earth), are as much
physiological necessities for the continuation of the species
as the processes we have just been discussing. We are
however here concerned with physiology in its narrower sense
and need not carry it so far as the branch of this science
known as sociology, the office of which it is to treat of these
questions.

694

PHYSIOLOGY

APPENDIX

A DESCRIPTION OF SOME ELECTRICAL INSTRUMENTS
USED IN PHYSIOLOGY

The first requisite of the physiologist, if he desires to use
electrical currents for excitation or any other purposes, is a
source of a constant current. For this two forms of batteries
are chiefly used, Daniell's and Grove's cells.

A Daniell's cell (Fig. 312) consists of an outer pot con-
taining a saturated solution of copper sulphate, in which is
immersed a copper cylinder. To the cylinder at the top a

Fig. 312.

Daniell's cell.

bindmg screw is attached, by which the connection of the
copper with a wire terminal is effected. Within the copper
cylinder is a second pot of porous clay, filled with dilute
sulphuric acid, in which is immersed a rod of amalgamated
zinc. In this cell the zinc is the positive and the copper
the negative ele7nent. Hence the current flows (in the cell)
from zinc to copper, and if the binding screws of the two
elements are connected by a wire, the current flows in the
wire (outer circuit) from copper to zinc, thus completing
the circuit. Since in the outer circuit the current flows
from copper to zinc, the terminal attached to the copper is

APPENDIX

695

called the positive pole, and that to the zinc the negative
pole.

When the current is required to be very constant, the
zinc may be immersed in a saturated solution of zinc sulphate
instead of dilute sulphuric acid.

A Daniell's cell, though very constant, gives only a small
current, owing to its small electromotive force and high
internal resistance. "When a stronger current is required, a
Grove's cell (Fig. 313) may be used. In this cell the zinc
is m the form of a cylmder, immersed in a cell containing
dilute sulphuric acid. W^ithin the cylinder is a porous pot
filled with strong nitric acid, m which is immersed a sheet
of platinum. In many cases the porous cell is made flat,

Fig. 313.

'€n

VPJ

Diagram of Grove's cell. Zn. Zinc cylinder, c. Inner porous
cell. T. Terminal or binding screw of platinum, e. Sheet of
platinum.

and the zinc plate bent up round it, in order to decrease the
distance between zinc and platinum, and so make the resist-
ance as small as possible. In this cell the zinc is the positive
and the platmum the negative plate ; and so the terminal
attached to the zinc is the negative, and that attached to the
platinum the positive pole.

Another very convenient form of battery, though not so
constant as the two forms just described, is the bichromate
battery, with a single fluid. This consists of a plate of zinc
between two plates of carbon. The whole are arranged so
that they can be immersed in or drawn out of the fluid at
pleasure. The fluid used is a mixture of sulphuric acid and
potassium bichromate. The wire attached to the carbons is

696 PHYSIOLOGY

the positive pole and the current in the outer circuit flows
from carbon to zinc.

Various forms of keys and commutators are used for
making and breaking a current, or for changing its direction.
Of these the only ones that we need here describe are Du
Bois Eeymond's key, and Pohl's commutator or reverser.
A Du Bois key consists of two pieces of brass, each of which
has two binding screws for the attachment of wires. These
are connected by a third piece, or bridge, which is jointed
to one of the two side bits, so that it may be raised or
lowered at pleasure {v. Fig. 314). It may be used either as
a simple make-and-break key, or, as is more usual, as a
short-circuiting key. In the first case one brass bank is
attached to one terminal, the other to the other terminal.
If the bridge be now lowered, the connection is made and

Fig. 314.

Du Bois key, closed. Du Bois key, open.

the current passes. If the bridge be raised, the current is
broken.

Fig. 314 A and b show the way in which the key is
arranged for short-circuiting. It will be seen that four wires
are attached to the key ; two going to the battery, and two
we may suppose going to a nerve. When the bridge is down,
as in Fig. 314 a, the current from the cell on coming to the
key has a choice of two routes. It may either go through the
brass bridge, or through the other wires and nerve. The
resistance of the nerve however is about 100,000 ohms,
whereas that of the bridge is not the thousandth part of an
ohm. When a current divides, the amount of current that
goes along any branch is inversely proportional to the resist-
ance. Here the resistance in the nerve-circuit is practically
infinite compared with that in the brass bridge, and so all

APPENDIX

G97

the current goes through the bridge and none through the
nerve. We say then that the current is short-circuited. If
however the bridge be raised, as in Fig. 314 b, the only way
the current can go is through the nerve, and so the whole
of the current takes this course. This form of key is indis-
pensable when exciting nerves with currents of high intensity.
If an ordinary make-and-break key only be interposed in the
circuit, excitation may occur even when the key is raised, the
current having high enough potential to complete itself
through the table and stand on which the preparation lies.

Diagram of Pohl's reverser.

This is called unipolar excitation, and obviously cannot occur
when the current is short-circuited.

PohVs reverser is an arrangement for changmg the direc-
tion of the current. It consists of a slab of ebonite or paraffin
or other insulating material, in which are six small holes
filled with mercury. A binding screw is in connection with
the mercury in each of these holes. Two cross -wires (not in
contact with one another) join two sets of pools together, as
shown in Fig. 315.

A cradle consisting of two wires joined by an insulating

698 PHYSiOLoaY

handle carries two arcs of wire by which the pools at (a)
and (b) may be put into connection with either (x) and (y), or
the corresponding pools on the opposite side. It will be
seen that with the cradle tipped to one side, as in Fig. 315 a,
the current from the battery enters the reverser at (a) ; this
proceeds up the wire of the cradle, down towards the right,
then along the cross-wire to the pool at (x). (x) is therefore
the anode, and (y) the kathode.

In Fig. 315 B the cradle has been swung over to the other
side. Here the cross-wires are not used at all by the current,
which passes from (a) up the sides and down the curved wire
to (y). In this case (y) is now the anode and (x) the kathode,
and the direction of the current through the circuit connected
with (x) and (y) is reversed.

By taking out the cross -wires, Pohl's reverser may be
used as a simple switch, by which the current may be led
into two different circuits in turn.

The Induction Coil {Bit Bois Beymond)

If a coil of wire in connection with a galvanometer be
placed close to (but insulated from) another coil through
which a current may be led from a battery, it is found that on
make and break of the current of the second coil a momentary
current is induced in the first. The induced current on
make is in the reverse direction, that on break in the same
direction as the primary current. The electromotive force of
the induced current is proportional to the number of turns of
wire m the coils. This principle is made use of in the con-
struction of the induction apparatus. This consists of two
coils, each containing many turns of wire. The smaller coil
(Ep Fig. 316), consisting of a few turns of comparatively
thick wire, is the primary coil, and is put into connection with
a battery. It has within it a core of soft iron wires, which
has the effect of attracting the lines of force, concentrating
them, and so increasing its power of inducing secondary
currents. The secondary coil, r.,, of a large number of turns
of very thin wire, is arranged so as to slide over the primary
coil. It is provided with two terminals, which may be con-
nected with the nerve or other tissue that we wish to stimu-
late. Since the electromotive force of the induced current is

APPENDIX

699

proportional to the number of turns of wire, it is evident that
the electromotive force of the current delivered by the induc-
tion coil may be many thousand times that of the battery
current flowing through the primary coil. The induced
currents increase rapidly in strength as the coils are ap-
proached to one another ; the strength of these therefore may
be regulated by shoving the secondary up to or away from
the primary coil.

A short-circuiting key is always placed between the secon-
dary coil and the nerve to be stimulated.

If only single induction shocks are to be used, a make-
and-break key is put in the primary battery circuit, and the

Fig. 316.

Diagram of inductorium. r,, primary ; e.,, secondary coil,
m. Electro-magnet of Wagner's hammer, w. Helmholtz'
side wire.

two wires from the battery and key are attached to the two
top screws of the primary coil (c and d, Fig. 316). It ia
then found that the shock given by the induced current on
break of the primary current is much stronger than that
on make.

In endeavouring to explain this difference in the intensity
of the make-and-break induction shocks, it must be remem-
bered that the intensity of the momentary current induced
in the secondary coil at make or break of the primary current
is proportional (1) to the number of turns of wire in each
coil ; (2) inversely to the mean distance between the coils

700

PHYSIOLOGY

{i.e. the nearer the coils, the stronger the induced current) ;
(3) to the rate of change in strength of the primary current.
Now, when a current is made through the primary coil, induc-
tion takes place, not only between primary and secondary coils,
but also between the individual turns of the primary coil itself.
This current of self-induction, being opposed in direction to
the battery current, hinders and delays the attainment by
the latter of its full strength, and so slows the rate of change
of current in the primary coil. Hence the intensity of the
momentary current induced in the secondary coil is less
than it would have been without the retarding effect of self-
induction.

Fig. 317.

(c^

At break of the current, an extra current is also produced
in the primary coil in the same direction as the battery
current, and therefore tending to reduce the rate of change
of the current from full strength to nothing. In this case
however the primary circuit being broken, the current of
self-induction cannot pass without jumping the great resist-
ance offered by the air, so that its retarding effect on the
rate of disappearance of the primary current may be prac-
tically disregarded. In Fig. 317 the line abed will repre-
sent the changes occurring in the primary current at make
and break, ct b corresponding to the make and c d to the
break. The lower line represents the momentary currents
induced in the secondary circuit, m being the current of low
intensity and long duration produced by the make, and B the

APPENDIX

701

shock of high mtensity and short duration caused by the
sharp break of the primary current.

When ^Ye desire to use faradic stimulation — that is,
secondary induced shocks rapidly repeated 50 to 100 times
a second — we make use of the apparatus attached to the
coil, known as Wagner's hammer (Figs. 316 and 318). In
this case the wires from the battery are connected to the
two lower screws (a and b. Fig. 316). Fig. 318 shows
the direction of the current when Wagner's hammer is
used. The current enters at (a), runs up the pillar and along
the spring to the screw (x). Here it passes up through the
screw, and through the primary coil (e,). From the primary
coil it passes up the small coil (m), and from this to the

Fig. 318.

Diagram showing course of current in inductorium when
Wagner's hammer is used.

terminal (b) and back to the battery. But in this course the
coil (m) is converted into an electro-magnet. The hammer
(h) attached to the spring is attracted down, and so the
spring is drawn away from the screw (x), and the current is
therefore broken. The break of the current destroys the
magnetic power of the coil, the spring jumps up again and
once more makes circuit with the screw (x), only to be drawn
down again directly this occurs. In this way the sprmg is
kept vibrating, and the primary circuit is continually made
and broken, with the production at each make-and-break of
an induced current in the secondary coil.

It is evident that, when the primary current is made and
broken fifty times in the second, there will be a hundred
momentary currents produced during the same period in the

702

PHYSIOLOGY

secondary coil. Every alternate one of these produced by
the break of current in the primary will be much stronger
than the intervening currents produced by the make. In
order to equalise make-and-break induction-shocks, so that a
regular series of momentary currents of nearly equal intensity
may be produced, the arrangement known as Helmholtz's is
used. In this arrangement the side wire (w), shown in
Fig. 316, and diagrammatically in Fig. 319, is used to
connect the binding screw (o) with the binding screw (c) at
the top of the coil. The screw (x) is raised, so as not to
touch the spring, and the lower screw (y) is moved up till
it comes nearly in contact with the under surface of the
spring. If we consider the direction of the current now, we

Fig. 319.

Diagram showing course of current when the Heimholtz
side wire is used.

see that it enters as before at the terminal, travels up
the Helmholtz's wire (w) to the screw (c), thence through
the primary coil (r,), then through the coil (m) of the
Wagner's hammer, and so back to the battery. The coil (m),
thus becoming an electro -magnet, draws down the hammer
(h). In this act the under surface of the spring comes in
contact with the screw (y). The current then has a choice
of two ways. It may either go through the coil as before, or
take a short cut from the terminal (a), up the pillar, along
the spring, through the screw (y), and down to the terminal
(b) back to the battery. As the resistance of this latter
route is very small compared with the resistance of the
primary coil, etc., the greater part of the current takes this

APPENDIX

703

way. The infinitesimal current which now passes through
the coil of Wagner's arrangement is insufficient to magnetise
this, and the hammer springs up again ; thus the process is
restarted, and the spring vibrates rhythmically. With this
arrangement the primary current is never broken, but only
short-circuited, and so diminished very largely. Hence the
retarding influence of self-mduction is as potent with break
as with make of the current, and the effects on the secondary
coil in the two cases are approximately equal. In Fig. 317
(c e) represents the change in the primary current when the
current is short-circuited instead of being broken, and (b)
represents the effect produced in the secondary coil. It will
be seen that the currents (m) and (b) are practically identical
in intensity and duration.

Fig. 320.

Diagram to show the mode of construction of a condenser.

Condenser. — If two plates of metal separated from one
another by a thin insulating layer of dielectric such as air,
glass, mica, or paraffined paper, be connected with the two
poles of a galvanometer, each plate acquires the potential of
the pole of the battery with which it is connected, and re-
ceives therefrom a charge of electricity (positive or negative).
If the connections be broken the two plates retain their
charge. If now they be connected by a wire they discharge
through the wire, and if a nerve be inserted in the course of
the wire, it may be excited by the discharge.

The amount of electricity that may be stored up in this
way will depend on the extent of the plates and their
proximity to one another, as well as on the e.m.f. of the

704 PHYSIOLOGY

charging battery. In order to get great extent of surface,
a condenser is built up as in the diagram (Fig. 320) of a
very large number of plates of tinfoil, separated by discs of
mica or paraffined paper. Alternate discs are connected
together : thus 1, 3, 5 are connected to one pole, while 2, 4,
6 are connected to the other.

The rheocord is used to modify the amount or strength of
current flowing through a preparation. One form of it is
represented in Fig. 321. A constant source of current at b
causes a flow of electricity from a to b through a straight
way. As the resistance of this wire is the same throughout
its length, the fall of potential from a toh must be constant.

The nerve, or whatever preparation that is used, is con-
nected with the straight wire at two points, at a and at c,

^^j^i^^>*=

by means of a sliding contact or rider. Supposing that
there is an electromotive difference of one volt between a and
b, it is evident that if c is pushed close to b, the e.m.f.
acting on the nerve will be also one volt. The e.m.f.
however may be made as small as we like by sliding c
nearer to a. Thus if a b is one metre, and there is a differ-
ence of one volt between the two ends, then if c be one
centimetre from a, the e.m.f. acting on the nerve will be
roo" volt. Thus we alter the current passing through the
nerve by altering the e.m.f. which drives the current.

The galvanometer is an instrument used to measure
strength of current. Its construction depends on the fact
that, if a small compass be suspended within a coil of wire
and a current be passed through the wire, the compass is
deflected, and tends to take up a position at right angles to

APPENDIX

705

its former one. In practice a pair of such magnetic needles
are usually employed, arranged reversely, as in Fig. 322,
where a and n represent the north-seeking ends of the
magnets a h and s n. On arranging them in this way the
effect of the earth's magnetism on them is weakened or
annulled, and they are spoken of as astatic. A bar compass
is suspended over the galvanometer, by the adjustment of
which the force with which the suspended pair of magnets
tends to ' set ' in one direction may be increased or dimi-
nished. In Thomson's galvanometer, as it is used for nerve
work, the coils of wire have a resistance of 5,000 to 20,000
ohms. Between the two magnets is fixed a small mirror.
The swing of the magnet is recorded by observing the

Fig. 322.

(3l>'

Diagram of galvanometer, with astatic pair of magnets. The
arrows show direction of current from battery, and the swing
of the needles.

excursion of a spot of light reflected by this mirror on to
a horizontal graduated scale.

In thermo-electric experiments, when very small differ-
ences of potential have to be measured through a small
resistance, the galvanometer must also have a small resist-
ance, which here should not be more than one ohm.

The capillary electrometer is an instrument for record-
ing and measuring difference of potential. That is to say,
if connected with two points, it measures the force which
would make a current flow between these two points if they
were connected with a wire.

Its structure is very simple. It consists of a glass tube
drawn out to a fine capillary point. This tube with the
capillary is filled with mercury. The pomt dips into a wide
tube containing dilate sulphuric acid, at the bottom of which
is a little mercury. Two platinum wires melted into the

45

706

PHYyiOLOGY

glass and dipping into the mercury serve as terminals. In
consequence of capillary attraction the acid ascends some
way into the capillary tube, and the force of this can,
with fine capillaries, sustain the weight of several inches of
mercury.

When the instrument is used, the meniscus of the mercury
in the capillary at its junction with the acid is observed
under the microscope, or a magnified image of it is thrown
on a screen with the aid of the lime or electric light.

Fig. 323.

• II''

.-acid

S-Hj?.

Diagram of capillary electrometer. Hg., Mercury. The two
terminals are rein-esented as leading off two points at the base
and apex of a frog's heart, a b.

If now the capillary and acid be connected with two
points, it will be observed that any difference in the potential
of these two points causes a movement of the meniscus. If
the point connected to acid be negative as compared with the
point connected to mercury in capillary, the meniscus moves
towards the point of the capillary. If the acid be positive
as compared with the capillary, the meniscus moves away
from the point. It is further found that the extent of the
excursion is proportional to the difference of potential.

Since the capillary electrometer appears to have no latent
period, and is free from instrumental vibrations, it is ex-
tremely useful in recording the quick changes in potential

APPENDIX 707

occurring in the diphasic electrical changes that accompany
every contraction-wave in the body.

The excursions lend themselves well to photography, so
that we may obtain a graphic record of every electrical
variation, and thus determine its extent and its time-
relations.

It must be remembered that this instrument is an electro-
meter (measurer of difference of potential), and not a galvano-
meter (current-measurer). When the electrometer is con-
nected with two points at different potential, no current passes
through it. Hence the use of non-polarisable electrodes is
not so essential in experiments with this instrument as when
we make use of the galvanometer.

45-

INDEX

Absokptiox of foodstuffs, 349-359

of lymph, 295
Accelerator nerves, 250
Acc-ommodation, 552
Adaptation, visual, 566
Adrenaline, 252, 520
Aerotonometer, 492
Air, changes of composition in respired,

386
Alanine, 32
Albuminoids, 46
Albumens, 39

derived, 40
Albumoses, properties of, 41
Alimentary canal, 8
Alveolar air, 388
Amboceptor, 85
Amino-acids, 33, 333, 437
Ammonia, excretion of, 488 450

formation of, 139
Amceboid movement, 157
Amyloid substance, 46
Amylopsin, 331
Anabolic nerves, 271
Anabolism, 4
Anacrotic pulse, 229
Ansemia, 285

Anaesthetics, action on nerve, 180
Anelectrotonus, 169
Antibody, 85
' Autipeptone,' 333
Apex-beat, 219
Aphasia, 663
Apncea, 417
Ai-ginine, 36
Arteries, extensibility of, 190

peripheral reactions of, 278

pressure in, 192

structure of, 189

Arteries, velocity in, 201
Aspartic acid, 34
Asphyxia, 404

influence on blood-pressure, 275
Assimilation, 4, 7, 26
Astigmatism, 560
Auditory sense, 544-549
Auerbach's plexus, 370
Auto-oxidisable substances, 28
Axon, 588

Basophile corpuscles, 61
Batteries, 694
Bidder's ganglia, 235
Bile, 338-346, 353

pigments, 343

source of, 69

salts, 341
Bilirubin, 343
Biliverdin, 343
Bladder, movements of, 469
Blood, 57-86

coagulation of, 75-84

composition of, 84

gases of, 391

reaction of, 84

specific gravity of, 84

total quantity of, 283

velocity of, 201
Blood-corpuscles, 58-74

chemistry of, 62-67

estimation of, 73

formation of, 70

life history of, 68
Blood-plasma, conditions of clotting, 83
Blood-platelets, 61, 83
Blood-pressure, 192

effect of asphyxia on, 275

in heart, 215, 227

710

PHYSIOLOaY

Blood-pressure, respiratory undula-
tions of, 423

Blood-serum, 75

poisonous effects of, 285

Blood-vessels, innervation of, 260
reflex alterations of, 271
structure and properties of, 189
velocity of blood flow in, 201

Brain, circulation in, 667

connecting tracts in, 626
functions of, 22, 642-652
localisation in, 656-663
membranes of, 666
structure of, 612-633

Bronchi, innervation of, 418

Calorimeter, 501

Cane-sugar, 54

Capillaries, circulation in, 280

permeability of, 290

velocity in, 204
Capillary electrometer, 125, 705
Carbohydrates, absorption of, 354

chemistry of, 51-56

metabolism of, 489-496

of milk, 509
Carbon dioxide in blood, 391

influence on respiratory
centre, 405

monoxide, 400, 420
Carboxyhaemoglobin, 64
Cardiograph, 220
Cardiometer, 255
Caseinogen, 44, 323, 508, 693
Cells, oxidative changes in, 28

processes of reduction in, 28
Cellulose, 56
Centre, cardio-inhibitory, 251

respiratory, 402

vaso-motor, 260
Cerebellum, 645-651
Cerebral circulation, 667

hemispheres, 653-665
Cerebro-spinal fluid, 666
Cerebrum, 22, 653
' Characteristic,' 101
Chemical constituents of the body,

25 et seq.
Cholesterin, 49, 343
Choletelin, 343
Chondrin, 46
Chondro-proteins, 46

Ciliary movement, 157
Circulation, 189-285

capillary, 280

course of, ] 1

influence of gravity on, 278

in lungs, 422
Circulation-time, 205
Coagulation, intravascular, 82

of blood, 75

of colloids, 31

of milk, 324

of muscle-plasma, 131
Coagulin, 86
Cold spots, 528
Colloids, 31
Colour vision, 572
Commutator, 696
Compensation in heart, 257
Complement, 85
Condenser, use of, 175, 703
Conduction in nerve, 169
Cones, 562, 567
Contractile tissues, 87-158
Contraction, isometric, 107

isotonic, 107

law of, 171

of heart muscle, 2

of muscle, 102

paradoxical, 186

propagation of, in heart, 237

wave, 108
Contrast phenomena, 575
Co-ordination, 15
Cortex, functions of, 656

structure of, 653
Cranial nerves, 634
Creatine, 36, 133, 441
Creatinine, 449
Crystallin, 40
Curare, action of, 95
Cutaneous sense, 526
Cystine, 36, 333
Cytase, 56

DEFiECATION, 375

Degeneration, 584

retrograde, 592
Deglutition, 363
Demarcation current, 121, 127
Depressor nerve, 272
Dextrin, 56
Dextrose, tests for, 53

IxN^DEX

711

Diabetes, 490

Diabetic coma, 495

Diamino-acids, 35, 333

Diaphragm, movements of, 379

Dicrotic wave, 226, 230

Diet, 507

Digestion, mechanisms of, 298-376

muscular mechanisms of, 363-
376
Diphthongs, 432
Di-saccharides, 54
Dissimilation, 4
Ductless glands, 5.13-521
Dys-oxidisable substances, 28

Ear, structure of, 544

Elastin, 47

Electrical changes in glands, 312
in muscle, 120
in nerve, 104
organs, 128

Electrodes, 98

non-polarisable, 120

Electrotonic current, 182

Electrotonus, 167

Emotional expression, Gol

End-plates, 92

Energy of nerve-stimuli, 175

Enterokinase, 331, 347

Eosinophile, 60

Equilibrium, maintenance of, 643

Erepsin, 304, 347

Excitation of muscle, 95

ExM-etion, 12, 375, 434

Eye, accommodation in, 552
adaptation of, 566
chromatic aberration of, 558
movements of, 568, 635
refractive media of, 552

Eye-ball, nutrition of, 580

F^CES, comiwsition of, 361
Fat, formation of, 485
Fatigue in nerve. 177, 188

of muscle, 141
Fats, absorption of, 350

chemistry of, 48-50

emulsification of, 336

of milk, 509
Ferments, 299-304
Fibrin, 75

precursors of, 78

Fibrin ferment, 80
Fibrinogen, 79

tissue-, 82
Foodstuffs, fate in organism, 478-512

heat-equivalents of, 482

Galactose, 54
Galvanometer, 704
Ganglia, reflex action in, 683
Ganglion cells, functions of, 680
Gases, irrespirable, 421

of blood, 391

respiratory interchange of, 386-
401
Gastric juice, 316
Gelatin, 46

influence of pancreatic juice
on, 335
Glands, see also Secretion

ductless, 513-521

salivary, 307

sebaceous, 473

sweat-, 474
Glaucoma, 581
Globin, 65
Globulins, 39
Glucosamine, 45
Glucose, 53
Glutamic acid, 36
Glycine, 34
Glycocholic acid, 342
Glycogen, 56, 489

in muscle, 133
Glyco-proteins, 44
Gycosuria, 492
Glycurcnic acid, 45, 492
Gracilis experiment, 164
Gustatory sense, 539

HiEMATIN, 65

Hffimatogen, 72
Hsematoidin, 67
Hsematolysis, 68
Hffimatoporphyriu, 67
Hsemin, 65
Hsemochromogen, 66
Hsemocytometer, 73
Hsemodromograph, 202
Hsemodromometer, 202
Htemoglobin, 58

compounds with gases, 62

crystallisation of. 62

712

PHYSIOLOGY

Hsemoglobin, destruction of, 68

estimation of, 74

fate of, B45

formation of, (J9

spectrum of, GG
Hffimoglobinometer, 74
HcTmolysis, 85, 285
Haemorrhage, effects of, 285
Hffimotachometer, 203
Hearing, 544-541)
Heart, action of asphyxia on, 275

afferent nerves of, 250

anatomy of, 20G

automatic power of, 235

compensation in, 257

frog's, anatomy of, 234

influence of drugs on, 251

mammalian, innervation of, 245
rhythm of, 242

negative pressure in, 218

output of, 253

pressure in, 215, 226

rliythm of, 233

work of, 253
Heart-beat, phenomena of, 210
Heart-impulse, 21'J
Heart-muscle, properties of, 236
Heart-sounds, 213

record of, 221
Heart-valves, action of, 211
Heat, production of, 501
Heat-formation in nerve, 165

in muscle, 114
Heat-spots, 528
Hemianopia, 661
Hexone bases, 33, 334
Hexose, 51
Hippuric acid, 449
Histidine, 36
Histones, 37, 42
Hydrobilirubin, 453
Hypermetropia, 560

Impregnation, 688

Induction coil, G98

Intiammation, 280

Inhibition, 607

effect of strychnine on, 607
of involuntary muscle, 156

Inogen, 138

Inosit, 133

Intestinal juice, 347

Intestine, large, innervation of, 374

movements of, 374

structure of, 349
Intraocular pressure, 580
Invertin, 304, 347
Iris, movemei:its of, 556
Irritability, 2

specific, 164
Islets of Langerhans, 329, 495
Isometric contraction, 107
Isotonic contraction, 107

Katabolic nerves, 271

Katabolism, 4

Katacrotic ijulse, 229

Katalytic phenomena, 29

Katelectrotonus, 169

Keratin, 47

' Kernleiter,' 183

Keys, 699

Kidneys, functions of, 434-466

innervation of, 464

metabolic functions of, 466

structure of, 454

work of, 464
Knee-jerk, 609

Lactase, 332
Lactation, 690
Lactic acid, 55

of muscle, 134
Lactose, 55

inversion of, 332
Lsevulose, 54
Lardacein, 46
Larynx, movements of, 429
Latent period of involuntary muscle,
149
of voluntary muscle, 105
Lecithin, 49
Leucine, 34, 333
Leucocytes, chemistry of, 73
emigration of, 281
formation of, 73

of fibrin ferment from,
82
varieties of, 60
Liver, secretion of, 338

formation of urea in, 438, 481
of glycogen in, 354, 490
of sugar in, 490, 492
Lungs, circulation in, 422

INDEX

713

Lungs, gaseous interchanges in, 38G-

401
Lymph, 286-297
Lymph-flow in plethora, 283
Lysine, 36

Maltase, 304, 336
Maltose, 54

Manometer, Hiirthle's, 216
max. and min., 217
mercurial, 193
Marey's law, 251
Mastication, 363
Menstruation, 687

Metabolism of carbohydrates, 489-496
of fat, 4S5-488
of proteins, 443, 478-484
Methajmoglobin, 64
Micturition, 467-472
Milk, coagulation of, 324
composition of, 508
secretion of, 691
Milk-sugar, 55
Millon's reaction, 38
Mono-saccharides, 51
Motor centres, 657

tracts in brain, 627
cord, 598
Mucins, 45
Mucoids, 4o
MiiUer's law, , 4, 518
Muscle, 14, 87 et seq.

absolute force of, 107
action of constant current on,
97
of drugs on, 142
chemical changes in activity,

135
chemistry of, 131
contraction of, 102
decomposition of creatin in,

441
direct excitability of, 95
effect of temperature on, 140
electrical changes in, 119
excitation of, 95
extensibility of, 111
fatigue of, 141
gaseous interchanges of, 138
heat-production in, 114
isometric contraction of, 108
isotonic contraction of, 107

Muscle, latent period of, 105, 149

mechanical efficiency of, 117
proteins of, 131
secondary contraction of, 130
source of energy of, 137
structure of, 87
tone of, 008

unstriated, physiology of, 149-
156
structure of, 89
voluntary contraction of, 145
work of, 113
Muscle-plasma, 131
Muscle-sound, 145
Muscles of frog's leg, 93
Muscular actions, co-ordination of,
643
energy, source of, 497
mechanisms of digestion, 363-
376
of micturition, 469
of respiration, 377
Muscular sense, 531

tone, 608
Myogen, 132
Myographs, 103-105
Myohsematin, 133
Myopia, 559
Myosin, 132

Negative variation, 122
Negativity, 125
Nerve, 159-188

conduction in, 169
degeneration in, 584
double conduction in, 163
effect of injury on, 179
electrical change in, 164
excitation of, 167, 171, 174
excitation of human, 173
fatigue in, 177, 188
heat-formation in, 165
influence of temperature on, 179

drugs on, 180
polarisation j)henomena in, 182
propagation in, 162
retrograde degeneration of, 5
structure of, 160
Nerve-cell, function of, 591, 680

structure of, 588
Nerve-cells of cord, 594
Nerve-centres in medulla, 641

714

PHYSIOLOGY

Nerve-degeneration, influence on vaso-
constrictors, 2()1)
Nerve-roots, 20, 582, 603
Nerves, cranial, 634-640
depressor, 272
pelvic, 374, 470
pilomotor, 474, 674
pressor, 272

secretory, to salivary glands,
313
to stomach, 326
splanchnic, action ■ on blood-
pressure, 267
on intestine, 367
origin of, 677
vagus, see Vagi
vaso-dilator, 268
vaso-motor, 260, 266
visceral, 21, 670
Nervi erigentes, 268
Nervous impulse, 162

nature of, 18, 187
system, 16, -582-681

visceral, 669-684
Neuroglia, 592
Neurokeratin, 47
Neuron, 590
Nissl's granules, 591
Nitrogen, assimilation of, 26, 478
Nitrogenous equilibrium, 483
Noend vital, 402
Nucleic acid, 43
Nuclein, 42
Nucleo-proteins, 42

injection of, 82

(Edema, inflammatory, 281
Olfactory sense, 541
Oncometer, 262
Ophthalmometer, 554
Ornithine, 36
Osazones, 52

Osmotic pressure, definition, 464
Oxidation in tissues, 396

mechanism of, 28
Oxydases, 29

Oxygen, influence of changes in ten-
sion, 407, 419

intramolecular, 139
Oxyhsemoglobin, see Haemoglobin
Oxyproline, 36, 333

Pain, 529
Pancreas, 328

sugar-function of, 495
Pancreatic fistula, 329

juice, action of, 331-337, 353
Paradoxical contraction, 186
Parathyroids, 519
Parturition, 689
Pelvic nerve, action on colon, 374

on bladder, 470
Pepsin, 325
Pei^tone-plasma, 83
Peptones, 42

properties of, 320
Phagocytes, 281
Phakoscope, 553
Phenyl-alanine, 36, 332
Phloridzin, action of, 493
Photoha-matachometer, 203
Pigments of bile, 343

of urine, 452
Pilomotor nerves, 474, 673
Pineal gland, 519
Pituitary body, 519
Plasma, blood, 58

muscle, 131
Plasmine, 79
Plethora, 283

hydrsemic, 294
Polarisation, 119

in nerve, 182
Polypeptides, 37, 335
Poly-saccharides, 55
Presbyopia, 560
Pressor nerves, 272
Proline, 36, 333
Protamines, 36
Proteins, absorption of, 355

chemistry of, 31-47

classification of, 38

conjugated, 42

crystallisation of, 32

disintegration of, 33

halogen derivatives of, 40

metabolism of, 443, 478-484

of milk, 508

of muscle, 131

pancreatic digestion of, 332

requirements of man, 483

tests for, 37
Prothrombin, 81
Protoplasm, definition, 5

INDEX

715

Pseudo-globulin, 76
Ptyalin, 304, 305
Pulse, 196, 223
Purine bases, 449

Reaction, 15

time, 606
Recurrent sensibility, 587
Reflex action, 17, 606, 642

in peripheral ganglia, 683
Refractory period, 240
Remak's ganglion, 235
Rennin, 304, 323
Reproduction, 685-693
Respiration, 12, 377-427

chemistry of, 386-401
cutaneous, 476
internal, 14

nervous mechanism of, 402
of muscle, 136
Respiratory quotient, 138, 387

undulations in blood-pressure,

423
interchange of gases, 386-401
Retina, functions of, 563
structure of, 561
Retractor penis, 149
Rheochord, 704
Rheoscopic frog, 130
Rheotome, 123

Rhythm of unstriated muscle, 150
Ribs, movements of, 380
Rigor mortis, 133
Rods, 562, 565

Saliva, 305-315

Salts, absorption of, 356

of urine, 451
Sarcolactic acid in muscle, 133
Sarcomere, 90
Sarcoplasm, 90
Sarcosine, 36
Sarcostyle, 90
Sebaceous glands, 473
Secretin, 330, 341

Secretion, histological changes during,
308, 325

paralytic, 315

relation to lymph production,
291

salivary, 307

Secretory nerves, to pancreas, 330

to salivary glands, 313
to stomach, 326
Semicircular canals, functions of, 535
Sensation, 522

auditory, 54 4

cortical representation of, 660

cutaneous, 526

gustatory, 539

olfactory, 541

muscular, 531

paths in brain, 631

in cord, 603
static, 534
temperature, 528
visual, 570
Senses, 522-581
Sensory areas, 660
Serine, 32
Skin, functions of, 473-477

sensory functions of, 526
Smell, 541
Soaps, 49
Speech, 428
Spliygraographs, 224
Spinal cord, 20, 582-611

nerve -cells of, 594
paths of impulses in, 603
reflex functions of, 606
structure and tracts of,

582-602
white matter of, 596
roots, degeneration of, 586
Splanchnic nerves, action on blood-
pressure, 267
on intestine, 367
origin of, 677
Spleen, 513

functions of, 515
relation to blood-formation,
72
' Staircase ' phenomenon, 239
Stannius' ligature, 235
Starch, 55
Static sense, 534
Steapsin, 304, 331
Stomach, digestion in, 316

movements of, 365
Stroma, 58

chemistry of, 67
' Stromuhr,' 201
Succus entericus, 347

716

PHYSIOLOGY

Sngar of milk, -55
Sugars, chemistry of, 51-5G
Summation in heart-muscle, 239
of contractions, 110
of stimuli, 151, (506
Suprarenal capsules, 520
Sweat, secretion of, 474
Sympathetic ganglia, effect of nicotine
on, 261), 083
nerves to lieart, 245, 248
system, 21, 670

vaso-constrictor action of,
266

Tambodk, 216

Tactile sensations, 526

Taste, 539

Taurocholic acid, 342

Tears, secretion of, 579

Temperature, regulation of, 501

sense, 528
Tendon phenomena, 609
Tension, influence on heart-muscle,
239

of gases in blood, 392
Tetanus, 111
Thermopile, 115
Thrombin, 80
Thrombogen, 82
Thrombokinase, 82
Thrombus, formation of, 83
Thymus gland, 516
Thyroid gland, 517
Traube-Hering curves, 277
Trypsine, 304, 331-335
Tryptophane, 36, 333
Tyrosine, 34, 334

Ukea, 435

origin of, 437-443
Uric acid, 444-449
Urine, composition of, 434

nitrogenous constituents of,
435-453

pigments of, 452

salts of, 451

Urine, secretion of, 454-466
Urobilin, 69, 452
Urochrome, 452

Vaoi, action on bronchi, 418
on heart, 247
on intestines, 372
on oesophagus, 365
on respiration, 409-418
on stomach, 367

cardiac branches of, 246

functions of, 640

secretory fibres of, 330
Vascular mechanism, 1 89-285

system, capacity of, 199
Vaso-dilator nerves, 268
Vaso-motor impulses in cord, 605

nerves, 260

course of, 266
Veins, extensibility of, 191

pressure in, 192

pulse in, 232

structure of, 190

velocity in, 204
Ventilation, 421
Veratrine, 142
Visceral nerves, 21, 670

nervous system, 670-684
Vision, 550-580

binocular, 567

colour, 572

stereoscopic, 579
Voice, production of, 431
Voluntary contraction, 145
Vomiting, 369
Vowel sounds, 431

WoEK of heart, 253
of muscle, 113

Xanthoproteic reaction, 38

Zymogen, 311

in pancreas, 331
in stomach, 325

PRIKTrn BY

SFOTTISWOODK AND CO. LTD., NEW-STREET SQUARE

LOKDON

A

4* '^n

COLUMBIA UNIVERSITY LIBRARIES

This book is due on the date indicated below, or at the
expiration of a definite period after the date of borrowing,
as provided by the rules of the Library or by special ar-
rangement with the Librarian in charge.

DATE BORROWED

DATE DUE

DATE BORROWED

DATE DUE

',. ■

• '»

ff< iitw*

} :

czeii i40)Mioo

i ..J-s^i

W'