Further advances in physiology

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_ FURTHER ADVANCES IN PHYSIOLOGY

UNIFORM WITH THIS VOLUME

SECOND IMPRESSION

RECENT ADVANCES IN
PHYSIOLOGY & BIO-CHEMISTRY

EDITED BY
LEONARD HILL, M.B., F.R.S.

CONTRIBUTORS

BENJAMIN Moore, M.A., D.Sc.
J. J. R. MACLEOD, M.B.
LEONARD HILL, M.B., F.R.S.
M. S. PEMBREY, M.A., M.D.
A. P. BEDDARD, M.A., M.D.

xii+744 pages. Demy &vo, 18s. net

LONDON: EDWARD ARNOLD

4 7 4
—_— -

URTHER ADVANCES IN
-- PHYSIOLOGY

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- wo bis

ia EDITED BY
4 LEONARD HILL, M.B., F.R.S.

j CONTRIBUTORS

_ BENJAMIN MOORE, M.A., D.Sc., Johnston Professor of Bio-
Chemistry in the University of Liverpool.

MARTIN FLACK, M.A., B.M., Demonstrator of Physiology, London
Hospital.

THOMAS LEWIS, M.D., D.Sc., Fellow of University College.
_ LEONARD HILL, M.B., F.R.S,, Lecturer on Physiology, London
Hospital.

ARTHUR KEITH, M.D., Curator of Museum, Royal College of
___.. Surgeons, England.
_ M. S. PEMBREY, M.A., M.D., Lecturer on Physiology, Guy’s
a Hospital.
_ N. H. ALCOCK, M.D., Lecturer on Physiology, St. Mary’s Hospital.
_ JOSEPH SHAW BOLTON, M.D., M.R.C.P., Fellow of University

College, London, Senior Assistant Medical Officer, Lancaster
_ County Asylum. ’

M. GREENWOOD, Jun., M.R.C.S., Senior Demonstrator of
Physiology and Director of Statistical Department, London

Hospital.

-
‘

WITH DIAGRAMS

LONDON
EDWARD ARNOLD
1909

(All rights reserved)

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Digitized by the Internet Archive
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PREFACE

THE volume now put before the reader by the editor is a sequel to
* Recent Advances in Physiology,” and deals with certain branches
of the science other than those dealt with in that volume, the
treatment of the subject-matter being, in both, on the same general
lines. The aim of the editor and his coadjutors has been to write

up their views on certain selected subjects which, both by their

importance and interest, will stimulate the student, give him a
view wider than that which the ordinary text-book can give him,
and at the same time rivet his attention on subjects which have a
particular application to Pathology and Clinical Medicine. While
the former volume dealt mainly with problems of metabolism,
secretion, and excretion, this is devoted to the consideration of
certain problems concerning the circulation and respiration, the
neuro-muscular system, and vision. Prof. B. Moore, writing on the
relation of the heart-beat to its nutritive fluid, has developed this
subject into a general consideration of the equilibrium of colloid
and crystalloid in living cells. “Mr. Martin Flack has discussed the
present position of the myogenic and neurogenic theories of the
heart-beat, and analysed the recent researches which have modified
the lines of thought on this subject. Dr. Thomas Lewis has given
the reader an account of the venous pulse, and those methods of
investigating the cardiac cycle in man which have done so much,
in the hands of Dr. James Mackenzie and others, to elucidate the

different forms of heart trouble. The editor has dealt, firstly, with

the wonderful advances in experimental method made possible by
Carrel’s surgical union of the blood-vessels ; secondly, with blood ~

_ pressure and its measurement in man. He has endeavoured to
_ refute the supposed importance of blood pressure as a mechanical
factor in the formation of lymph, production of dropsy, excretion of

1
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urine, &c. Dr. Arthur Keith has contributed an account of his
researches into the mechanisms of breathing, and thereby has upheld

the importance of anatomy treated as a study of function. Dr. —

Pembrey has given an account of the subject he knows so well—
the Physiology of Muscular Work—and has incorporated therein the
new results which have been obtained, particularly in this country,
by the study of marching soldiers. The present views held con-
cerning the growth, regeneration, union of nerves, and the nature of

the nerve impulse, have been considered by Dr. N. Alcock; while ~

Dr. J. S. Bolton has contributed an account of the recent researches
of himself and others on cortical localisation and the functions of

the cerebrum, including the revolutionary views which have been -

put forward concerning Broca’s localisation of Aphasia. Lastly, Mr.
Major Greenwood has dealt with two especially interesting subjects
of sense physiology—Visual Adaptation and Colour Vision. Each
writer is responsible for the views he has set forth and the treatment
of his subject, and the editor has done no more than select his
-coadjutors, write his own part, and arrange the book for the press.
He hopes it may meet with as cordial a reception as the first
volume, serve a useful part, and be perhaps the forerunner of
still other volumes, of “more” and “ most recent,” and even
“ furthest’ Advances in Physiology.

OsBoRNE House, LOUGHTON,
March 7, 1909.

CONTENTS

7?
+ By BENJAMIN MOORE
THE EQUILIBRIUM OF COLLOID AND CRYSTALLOID IN LIVING

PAGE

By MARTIN FLACK
a, rer, * |

By THOMAS LEWIS

PULSE RECORDS IN THEIR RELATION TO THE EVENTS OF THE
HUMAN CARDIAC CYCLE . : : : : : : - 42

By LEONARD HILL
THE VASCULAR SYSTEM AND BLOOD PRESSURE . . « . 112

| By ARTHUR KEITH
THE MECHANISM OF RESPIRATION INMAN . . ..—..:sOXAR2

| By M,°8. PEMBREY
THE PHYSIOLOGY OF MUSCULAR WORK . . . . «208

By N, H, ALCOCK
ME CHAPTERS ON THE PHYSIOLOGY OF NERVE . « « £83

" By JOSEPH SHAW BOLTON

RECENT RESEARCHES ON CORTICAL LOCALISATION AND ON
THE FUNCTIONS OF THE CEREBRUM. . . .-. . 284

By M, GREENWOOD, Jon. os a
N SPECIAL SENSE puvsiology . . . . 2 &

FURTHER ADVANCES IN PHYSIOLOGY

THE EQUILIBRIUM OF COLLOID AND
CRYSTALLOID IN LIVING CELLS

By BENJAMIN MOORE

THE living cell may be regarded from the physico-chemical point
of view as a machine or mechanism through which there constantly
: is taking place a flux of energy. The cell is continually taking
energy up from its surroundings in certain forms, and redistribut-
{ ing this energy in other forms, but in the process it itself under-
' goes little or no permanent change. Certain changes, it is true,

do occur slowly in the cell in the course of its life-history which
have the effect of permanently altering the character of the energy
discharged through it; but these structural changes are so slow that
they can be put aside in the study of the cell as an energy machine
acting upon the energy supply at any given moment.

If the case of the green plant cell acting as an energy trans-
former for light energy be placed on one side, it may be stated that
the energy supplies of the cell always come to it in the form of
organic compounds capable of yielding energy in the process of
oxidation in the cell.

In order that the cell may be capable of oxidising these
chemical compounds of organic character coming in from its
environment, it is, however, absolutely essential that its own in-
tegrity be preserved ; and this integrity is just as completely de-
pendent upon the presence of the ions of certain simple inorganic
salts in the cell and its surrounding fluid media, as the exhibition —

of the typical phenomena of cell activity is upon the supply of

energy in the form of the organic compounds to the living cell.

In fact, in point of time, the physiological activity of the cell is

rapidly destroyed by removing or altering the supply of
: A

4 4

2 THE EQUILIBRIUM OF COLLOID AND i

inorganic ions, than it is by interfering with the supply of organic
foodstuffs. For, in the latter case, the cell can oxidise the com-
bustible materials present in storage within it, and even use up a
portion of its own intrinsic substance before its activities come to

a standstill ; but when the inorganic ions, forming a constitutional

part of the living cell, are altered, and the equilibrium between ‘
protoplasm and ion thus destroyed, the cell activities are imme-
diately affected, and after a short period of pathological activity
everything comes to rest.

An analogy with another form of energy transformer may
make this clearer. If the fires are banked under the boiler of.a
steam-engine the head of steam in the boiler will for a longer or
shorter period keep the steam-engine going, this is comparable to
stopping the organic food supply of the cell; but if there is a
sudden burst in the boiler, if the cylinder blows off, or if there is
a break in any essential part of the machinery, then there is a -
sudden stoppage of the engine, often preceded by a very brief
period of excessive activity: this is comparable to interference
with the inorganic ions of the cell. The inorganic ions form in fact
an intrinsic and indispensable part of the cell’s structure, in the
absence of which it can no longer utilise its food supply, however
abundant that supply may be, or suitably adapted for the nutrition
of the normal cell.

These effects, although they may be demonstrated in any living
tissue, are seen perhaps most typically in the case of the isolated
and perfused heart muscle. If the fluid caused to flow through
the heart consists of distilled water, to which organic foodstuff,
in the form say of dextrose, has been added, the heart beat ceases
almost instantaneously. If next the experiment be repeated upon
a fresh heart, using instead a solution of pure sodium chloride
in distilled water, of such concentration that it is isosmotic with
the natural serum of the animal, there ensues a considerably longer
period of perhaps some minutes’ duration before the heart beat
disappears. The sodium chloride solution, however, although
possessing the proper osmotic pressure, is unable for any con-
siderable time to preserve the heart muscle cells in normal con-
dition. By supplying the proper osmotic concentration it has
prevented the cells being suddenly broken up, but it has a zero ©
pressure for certain ions indispensable to the heart’s activity 5 .
thelis : have slowly diffused out, and the period of the heart’s action

GRYSTALLOID IN LIVING CELLS 3

has been determined by that moment at which the concentration
in the protoplasm has reached a certain minimal value.

: The most important of the ions which have been washed out
of the cardiac muscle cells by the current of pure sodium chloride
solution are the potassium and calcium ions. It still possesses
abundance of combustible organic material to furnish the energy
for its contractions, but the structural mechanism or machine for
oxidation has been interfered with and the cells can no longer
draw on their supply of stored energy.

That this is the true state of the case is shown by the effects
of adding quite minimal traces of soluble salts of calcium and
potassium to the pure sodium chloride solution, when the spon-
taneous beating of the heart commences and goes on for hours,
_ and even days, in a regular and automatic manner.

The amounts of potassium and calcium salts necessary to
bring out this profound difference in behaviour of the heart muscle
are strikingly small, the optimum amount of potassium chloride
required being only about 1 part in 10,000. More than an
exceedingly minute trace must not be added or the heart will
be stopped by the excess. There is only a certain range of con-
centration which must not be passed in either direction or the
heart will not beat normally. The meaning of this range will be
pointed out later.

These important experimental results were first demonstrated
by Sidney Ringer in the case of cardiac muscle of the frog heart ;
the complete generality of their application in all cells and tissues,
and the causes underlying them, are only in recent times becoming
generally appreciated, but the delicate and lightly balanced labile
equilibrium between the colloids of the cell protoplasm and the
osmotic pressures or concentrations of the inorganic ions and

_ other crystalloid constituents is perhaps the most important and
fundamental fact in the whole of biology.

____The inorganic ions are sufficient in the case of the more slowly

oxidising cardiac muscle of the heart of the cold-blooded animal
_ to maintain for lengthened periods an automatic rhythmic beat ;
_ the sufficient amount of oxygen for the oxidation being capable.
_ of being carried at the partial pressure of one-fifth of an atmos-
_ phere that the atmospheric oxygen possesses, and the combustible
| _ organic material coming from the store in the cardiac muscle cells.
But in the case of the mammalian heart, the oxygen pressure

4 THE EQUILIBRIUM OF COLLOID AND .

must be increased to nearly a whole atmosphere of pure oxygen
by bubbling oxygen gas through the Ringer’s saline heated to
mammalian body temperature in a flask attached to the perfusion
cannula, before a normal heart beat can be obtained. This in-
creased oxygen pressure supplies the place of the red blood cor-

puscles which in the body are able to carry a sufficiency of oxygen ~

at the lower pressure of oxygen present in the lungs. Also, in
the case of the mammalian heart for a prolonged experiment, it
is well, as recommended by Locke, to add dextrose to the Ringer’s
solution to prevent exhaustion of organic combustible material
which occurs earlier in the case of mammalian muscle on account
of the greater expenditure of energy which here occurs at each
heart beat.

Before leaving the classical example of cardiac muscle for
more general considerations, the similar action of anesthetics may
be mentioned as an example of the relationship of drugs to the
cell-protoplasm.

The conditions which govern the action of chloroform upon
the isolated mammalian heart have been beautifully demonstrated
by Sherrington and Sowton. These observers have shown that
at a fairly definite concentration of chloroform in the circulating
saline the heart beat becomes affected, and if this concentration
be passed the beat is stopped. If now the chloroform be cut off
and pure Ringer’s solution be perfused instead of it, after a short
time sufficient to reduce the osmotic pressure of the chloroform
in the cardiac cells below a definite limit, the heart recommences
its beating, and soon becomes normal once more. The conditions
of action here are obviously the same as in the case of the in-
organic ions above mentioned, except that the result is reversed,
and whereas in the case of the inorganic ions a certain pressure
or concentration of ions was essential in order to keep the heart
functionating normally, here a certain pressure of anesthetic is
required to still its activities. As soon as the osmotic pressure of
the anesthetic passes below a certain limit, the cells cease to be
anesthetised. In other words, some grouping in the protoplasm
is free from the anesthetising influence and open to continue other
chemical interchanges which give rise to its activity. Within
certain well-marked limits there is a certain reduced activity or
anesthesia. On one side of this is free activity or absence of
anesthesia ; on the other side there is complete anchoring of proto-

CRYSTALLOID IN LIVING CELLS 5

plasm by anesthetic or complete bondage from oxidising activity,
resulting finally in death of the cell.

The action of chloroform upon nerve cells in the production of
surgical anesthesia is shown, by the known physiological effects
connected with induction of and recovery from anesthesia, to be

similar in nature, and hence in producing safe anesthesia we stand
; upon that bridge or interval of partial combination between proto-
| plasm and anesthetic, where there is just sufficient combination
between the two to produce the stilling of activity which gives
the absence of pain, but not sufficient to cause complete stilling
of activity nor that degree of combination which cannot become
reversible and dissociate off when the pressure of anesthetic is
| lowered by discontinuing the administration and allowing the

- process of respiration to lower the pressure of anesthetic in the

nerve cells.

There is fortunately here, as in the case of all drugs, a degree
of selective absorption by different types of cells, and the cells of
the higher nerve centres are affected before other lower centres,
and these again before cardiac and other forms of muscle cells.
It is on this selective effect that all the benefits of anesthesia as
an accessory of surgery depend, for if the heart, for example, were
affected at the same level of concentration of the anesthetic as the
higher nerve cells, anesthesia would become impossible. Precisely
at the same moment as anesthesia set in the heart would stop
beating.

In general terms it may be stated that the actions of all specific
drugs depend upon this delicate selective action between the cells
of different tissues, or parasitic cells, and the drugs. The problem
of practical therapeutics is to find a drug or chemical combination
which by its peculiar chemical conformation is capable of under-
going adsorption at a lower pressure by a specific type of cell

protoplasm. This subject will be treated more in detail later on
when we have considered the general conditions governing the
relationships of the protoplasm to crystalloids, and to the other
substances with which it is brought in contact in the cell either
naturally, or as the result of disease, or in the treatment of disease.
We may now turn to a consideration of the general chemical

nature of protoplasm in so far as this bears upon its power of

adsorbing or combining with inorganic ions or other substances
_which may be present in common with it in the living cell.

6 THE EQUILIBRIUM OF COLLOID AND

The most essential and as it were the central constituents in
building up the excessively complex physico-chemical. aggregation
which we term protoplasm or bioplasm, are the protein bodies.
By means of the proteins, the fats and carbohydrates are knitted

together with the variously constituted proteins themselves and.

with the ions of the inorganic salts to form a united system. The
component parts of this system are only lightly held together,

each is held in by the pressure of a free portion of it in the cell .

fluid, and for the life and activity of the cell it is essential that
the osmotic pressure of each constituent should lie within a certain
range, so that it neither becomes fixed quite permanently nor so

completely liberated as to be absent from the cell when it is required ‘

for the chemical transformations which yield the supply of energy
to the cell. During the molecular vibrations which accompany
this labile equilibrium in which the intensities of attachment of the
various constituents to the bioplasm are all the time varying, the
organic oxidisable substances, viz. the proteins themselves, the
fats and carbohydrates, suffer temporary molecular disruptions
during which the oxygen also held in the bioplasm comes into
union with them, and the oxidised products as they increase in
pressure are shed off from the cell.

As has been stated above, the inorganic ions exercise the
function in the cell of favouring these chemical disruptions, for
when by lowering their osmotic pressure in the cell fluid they are
dissociated off from the bioplasm, the oxidation processes which
form the chemical basis for the cell’s activities also come to
an end.

Although’ it is impossible at the present time fo lartificially
synthesise any of the proteins of the cells or body fiuids, and still
less to build these up synthetically with the other constituents
mentioned above into bioplasm, or living matter, yet we have even

now obtained much insight as to the general character of the con- .

stitution of proteins, and the main plan upon which details are
still to be worked out lies before us.

This knowledge has been arrived at by two different channels
of approach, viz. that of studying the cleavage products of proteins
in which Schiitzenberg was the great pioneer, followed by a host
of others; and that of building together such cleavage products
_ into bodies closely resembling in many respects the naturally
occurring proteins, in which Emil Fischer is now ‘aging the way,

CRYSTALLOID IN LIVING CELLS 7

and, by the synthesis of the polypeptides, has already shown the
lines on which proteins must be built together.

Under the influence of hydrolytic agents, such as heating with
either alkalies or acids under pressure, the proteins take up the
elements of water and yield a large number of simpler organic
substances ; and conversely by the action of dehydrating or con-
densing agencies these simpler organic substances or organic
radicles of the proteins can again be made to unite. In the latter
direction the process cannot be carried back quite to that degree
of complexity which yields the naturally occurring protein, mainly

constituents is so delicately balanced that the chemical manipula-
tions cause splitting off and decomposition.

. The synthesised products are in fact hepa to possess that
delicately balanced power of associating and dissociating which is
characteristic in still higher degree of living matter, and it is for
this reason that only the living cell has hitherto been able to put
the finishing touches upon the delicate unions which finally yield
proteins, and beyond these up to living protoplasm, where the
complexity and corresponding instability reach their acme.

The organic radicles, which form the building stones, so to
speak, for the structure of the protein molecules, may be divided
into three classes, viz. those which are purely organic bases, those

- which are entirely organic acids, and a third and most characteristic
class which possess both the properties of organic acids and organic
bases in modified degree. The compounds of this third class are
known as the amido-acids, and it is to them that the proteins owe
their peculiar property of building up into such complex bodies
of high molecular weights.'_ The simplest type of amido-acid con-
tains one organic acid radicle and one basic radicle, the acid
character being given by the carboxyl group (COOH) and the

d basic character by the amidogen group (NH,). As the simplest

example, glycocoll or glycene, which is the amido-acid of acetic

acid, may be quoted. Acetic acid is CH,.COOH, and is purely
acid in its properties, combining with bases such for example as

ammonia, instead of neutralising the carboxyl group, becomes
_ attached, with the loss of one atom of hydrogen, as the group

1 The terms amido-acid and amino-acid have the same meaning, and are used
indiscriminately in describing members of this class of compounds.

because at that level the degree of chemical association of the:

ammonium to form ammonium acetate (CH,.COO.NH,). If the

e

8 THE EQUILIBRIUM OF COLLOID AND

amidogen (NH,) in the methyl group (CH,), there is formed instead
the body CH,(NH,).COOH which is the amido-acid. The carboxyl
group (COOH) being still free, the amido-acid retains acid properties,
but in lessened degree, on account of the presence in the molecule
of the basic group (NH,). The presence of the basic group also at
the same time confers the properties of a base, so that the amido-
acid now has the peculiar property of being able to functionate
either as acid or base. Thus with copper it forms a deep blue
soluble compound called copper glycocoll, and when in union with
other organic acids it forms well-known and important substances
found in the body, for example, the compound with benzoic acid
known as hippuric acid, and the compound with cholalic acid
occurring in the bile as glycocholic acid.

Amido-acids possessing only one amidogen group are termed
mon-amino-acids ; others exist possessing two such basic groups
in their molecule, and these are called di-amino-acids. A number
of both classes occur amongst the products of hydrolytic cleavage
of the proteins. Again, there is in the majority of cases only one
acidic or carboxyl group, but there are sometimes two or more
such acid groups, and then the amido-acids are referred to as
mono- and di-basic, &c., as in the case of ordinary organic acids.

The most striking chemical characteristic of all these amido-
acids, and that which from the point of view of protein formation
interests us most at present, is that of undergoing conjugation or
condensation with one another or with other organic bodies to
form long chains in single series, or it may be main chains with
side or branch chains arising from them.

In each union of this kind the elements of a molecule of water
are eliminated, a hydrogen atom being yielded by one of the two
combining molecules and a hydroxyl radicle by the other, and in
the great majority of instances the union occurs between the
amidogen group of one and the carboxyl group of the other.

For the reader who is not acquainted with the technical terms
of organic chemistry, the nature of the process of combination to
form protein, and further of proteins to form bioplasm, may be
illustrated by the use of electrical terms. The amido-acid, on
account of its possessing both an acidic and a basic group, may
be considered as possessing a sort of polarity (indeed it does possess
a kind of chemical polarity) ; as a result of this polarity a chemical
' attraction exists between acidic pole and basic pole of different

CRYSTALLOID IN LIVING CELLS 9

molecules, so that these tend to unite with the elimination of the
elements of water above mentioned. Now it is clear, since each
combining amido-acid had two free poles, that after this union has
occurred there will still be left, in the new combine of double the
molecular size, two opposite poles free ; and if this larger new mole-
cule is brought, under suitable conditions, in chemical contact with
more molecules, that further additions of like nature can occur.

If it be remembered that a certain number of the amido-acids
possess more than one basic group, or more than one acidic group,
it is further obvious that it is not necessary for this process of
growing to extend out in a single chain; but that branching may
occur, and union of branches, so that a ramification or network can
be formed in all three dimensions of space. ‘

There is no limit but the stability of the whole chemical system
to this growth proceeding until a point is reached at which, with
the particular chemical agencies for union and condensation at
‘hand, there is an equilibrium between the forces building up or
synthesising and the forces tending to disrupt.

In the same way by protein unions the substances of the pro-
toplasm or bioplasm can be formed, until new limiting conditions
again fix a maximum, and, it may be added, though the agencies
at work may differ in type, similarly the bioplasm can increase in
aggregation until a maximum cell volume has been feached for
a particular cell, and cell division becomes essential for further
multiplication.

In this process of growth it will be observed that there must
be left at the end of the process a number of poles of opposite
type. These poles, although they are chemically saturated (for as
pointed out above the elimination of the elements of water are
required at each union), must still possess what has been termed
residual affinity,’ and have sufficient power to attract a group of
opposite polarity and hold it very loosely attached.

? This residual chemical affinity is seen when compounds, saturated as regards
ordinary chemical values, combine with one another, such as neutral salts with
their molecules of water of crystallisation, The energy of such residual combina-
tions is seen when dehydrated salts-are dissolved in water, for this process always -
causes heat development although the crystallised salts after the residual combina-
tion is once completed always cause cooling when dissolved on account of energy
going latent as osmotic energy from development of pressure! in the given volume
of water. Similar heat effects are seen in dissolving alcohol in water, and in the

} Pressure signifies in this artiele osmotic pressure.

*fa/s ‘a4
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10 THE EQUILIBRIUM OF COLLOID AND

When this feeble attachment has once occurred it may become
altered.in different ways. First, if the growing protein aggregation |
has not yet reached its full size, there may be a swing into true
chemical union with the elimination of a water molecule.

If chemical union does not take place, a diminution of pressure
of one of the constituents may occur, causing dissociation or dis-
ruption, or conversely an increased pressure may lead to firmer
attachment, increasing association at the expense of dissociation,
and favouring chemical combination.

The form of union described above as “ feeble union ” or union
by “residual affinities ” is usually spoken of as adsorption, although
often a number of processes which may be dissimilar in nature are
placed together under this term.

Thus, the invisible layer of moisture that collects on the surface
of glass ; the adhesion of gases on the inner surface of glass vessels
which are in process of exhaustion; the moisture taken up by
textile fabrics; the gases occluded by certain metals such as
platinum, palladium, and iron; the concentration of dyes upon
the surfaces of fibres and tissues being dyed ; the union or adhesion
between inorganic salts or other crystalloids and colloids of various
kinds—these and a great many other phenomena are variously
given as examples of adsorption, and it is maintained that this
process is physical in character and essentially different from
chemical. combination.

If extreme cases of adsorption on the one hand and of chemical
combination on the other be taken for comparison, it becomes
obvious at once that there exist great differences between them.
Such, for example, as the hygroscopic absorption of water com-
pared with the combination of hydrogen and oxygen to form
water. In the former case the glass remains unaltered, and by
heating or by drying agencies the water molecules can be removed
unaltered from the surface ; while in the latter case, the water is
quite different in all its physical and chemical properties from

solution of free acids and caustic alkalies in water. Other examples are the union

of anesthetics such as chloroform with proteins, where the chloroform or other

anesthetic is in all cases a chemically saturated body, yet the proofs of union

with protein are indisputable, there being finally obtained with sufficient pressure

of chloroform actual precipitation, the precipitate containing chloroform in high

percentage. c
Other examples are the dyeing of tissues and fabrics by dyes, where a saturated

dye combines with a saturated colloid substratum. In all such cases the best effects

are obtained when the chemical sign of dye and substratum are opposite. —

>

_

,
|

CRYSTALLOID IN LIVING CELLS 11

either of the two gases which have, united with great evolution of
energy to form it.

But if the comparison be made between chemical reactions
and adsorptions which lie closer together, it is found that the
characteristic differences become diminished in degree, there are
all possible gradations, and many instances in which it is impossible
definitely to say whether the union which takes place ought to be
described as an adsorption or a chemical combination.

If the various criteria of a physical or chemical nature which
are usually taken as decisive of whether any union is a chemical
combination or an adsorption be examined critically, it is found
that they one after another break down.

To take an example of interest to the biologist, it was taught
for many years in all the physiological text-books that hamo-
globin formed with oxygen an easily dissociable compound. The
chemical combination was said to be complete at a certain pressure
of oxygen, and as the oxygen pressure fell, this compound, called
oxy-hemoglobin, dissociated off into oxygen and hemoglobin or
‘reduced hemoglobin,” the dissociation occurring over a definite
range of pressures. So certainly established were the facts regard-
ing this that the proofs of the formation of the compound formed
a stock question of the examination room. One of the strongest
proofs of this formation of the compound oxy-hemoglobin was
supposed to be that the amount of oxygen absorbed by hemoglobin
was not directly proportional to the partial pressure of the oxygen,
absorption occurring in relatively greater amount at the lower
pressures and falling off rapidly to nearly a zero increment as the
dissociation range was passed. So that when oxygen pressures
were graphically plotted as abscissee and amounts absorbed as ordi-

-nates, instead of a straight line, as, say, in the case of absorption

of oxygen (or other inert gas) by water, a curve was obtained.

But recent research has shown that in many. cases where the
phenomena ought to be classed under the head of adsorption, the
plotted curve of pressure (or ‘concentration) and of amount ab-
sorbed is not a straight line but a curve, and hence the new criterion
is not a simple linear relationship between concentration and
amount absorbed, but that the plotted curve shall show kinks or
breaks upon it, that is to say, regions at which there is a sudden
change i in the equation of the curve. Now the oxygen-hemoglobin

curve is a smooth curve, and for this reason it has apoenaly. been

12 THE EQUILIBRIUM OF COLLOID AND

maintained by Wolfgang Ostwald that in the case of oxygen and
hemoglobin the phenomena is one of adsorption. Yet in the case
of oxygen and hemoglobin there exists at the point where absorp-
tion is complete an exact stochiometric relationship of one molecule
of oxygen to one molecule of hemoglobin, the molecular weight of
hemoglobin being fixed by the iron determinations which can be
carried out with great exactitude. Now the existence of exact
stochiometric relationships is usually supposed to be one of the
strongest criteria for chemical combination. Further, there is
the very definite and distinctive oxy-hemoglobin spectrum, quite
definitely different from that of “reduced hemoglobin,” and the
fact that other gases, such as carbon-monoxide, replace oxygen
at saturation point in exactly equal volume to the oxygen required
to saturate.

It would appear from this conflicting evidence that the form
of the pressure absorption curve as a criterion between adsorption
and chemical combination breaks down, rather than to be proved
that the uptake of oxygen by hemoglobin is adsorption and not
chemical combination.

The other supposed criterion that there shall exist simple
stochiometric relationships at the saturation point between the
two substances uniting also breaks down in the case of unions
between colloids and crystalloids for several reasons.

For the appearance of absence of stochiometric relationship
may be fallacious, and there may be such relationships quite de-
finitely and true chemical union where there is apparently absorp-
tion, because the total mass of the colloid may not be identical or
proportional to its active mass. For example, the crystalloid, such
as a dye, may not penetrate the aggregate of the colloid, and the
chemical reaction may occur on the surface of the colloid only ;
and since it is impossible to estimate the active mass lying on the
surface and participating in the reaction, exact relative molecular
masses may be involved and yet there be apparently no such
relationships. Conversely, there may be no true chemical union,
and yet the masses of the two substances bear quite definite mole-
cular relationships. For, if we consider, for example, the protein
molecule, with a given number of amidogen groups each chemically
saturated as to valency, and yet each possessing a certain residual
amount of basic affinity, and if now to this protein we add in
increasing quantity a substance with weak and chemically saturated

CRYSTALLOID IN LIVING CELLS 13

acidic groups, then we have a definite number of anchorages, and
when the saturation point of absorption is reached there must appear
stochiometric relationships although there has occurred no con-
densation, and breaking apart would readily take place if the osmotic
pressure or concentration of either constituent were reduced.

In this way a salt which crystallises with water of crystallisation
has exact stochiometric relationships with the water, and yet the
water and salt, which are both saturated compounds, can only be
held together here by residual affinities.

To carry this short sketch of the controversy as to adsorption
versus chemical combination into detail would lead us far beyond
the limits of this article, so we may sum up with the statement that
between bodies of different chemical constitution there are varying
grades of affinity for union. At the one end of the scale there
are the typical chemical compounds, and at the other the more
physical unions ' of a weaker type, and dependent upon the main-
tenance of certain appreciable pressures or concentrations of the
substances uniting, which have been called adsorptions:; but
between these two there are all possible gradations, just as there
are all possible stages between crystalloids and colloids.

Whether the theories and terminology of adsorption be accepted
or those of the formation of easily dissociable chemical combination,
or the middle view be taken that in some cases one occurs and
in other cases the other, the important experimental fact which
remains indisputable is that a type of union occurs which is only
stable so long as a certain pressure (concentration) is maintained,
and breaks up as the pressure diminishes, showing a range there-
fore at which association and dissociation of the union occurs in
a fluctuating way accompanying variations in pressures within the
range.

1 A great deal has been written as to the mode of physical union and how it
is brought about. It has been shown that any substance which lowers the surface
tension at a bounding surface or interface will tend to increase in concentration
at that surface. In this way the formation of surface films of protein and other
colloidal solutions can be explained, similarly the formation of a layer of dye on
a fabric may meet with explanation, dnd a great many if not all other cases of
adsorption. But the question remains, why does the substance lower the surface
tension ? and the view is still tenable that the surface tension is lowered beeause
of chemical affinity for the substance forming the surface, or because the conditions
on the surface favour chemical condensation of the substance to form larger mole-
cules or aggregates than in the body of the solution. Also, an attraction of residual

affinities may attach the substance by adsorption, and after this anchorage true
chemical union may follow,

<<;

14 THE EQUILIBRIUM OF COLLOID AND

This type of union occurs par excellence, and in endless variety,
both as to number of substances so uniting and ranges of pressure
for union and disunion in the case of colloid with crystalloid,.and
in particular in living cells. Also in the building up of protein
and bioplasm, there occur endless varieties in the modes of group-
ing of the constituent radicles, which give rise to the selective
affinities of the cells, and cause one cell to enter into selective
union with one constituent of the plasma at a different level of
pressure (concentration) from another, or to possess affinities of such
a difference in order, that a substance is taken up with avidity
by one cell and apparently refused altogether by another. The
groups in cell and in substance entering into union with it are
often so delicately arranged that the change of a single radicle
alters the result entirely ; as, for example, in the action of strychnine
at very low pressure upon the nerve cells of the central nervous
system changing at once and practically disappearing when a -
methyl group is added to the strychnine molecule, or the more
slightly poisonous action of piperidine passing into the most virulent
action of coniine, when a propyl group (C,H,), in itself a harmless
enough constituent, replaces one of the hydrogen atoms as a side
chain.

We may now pass to the consideration of the evidence that the
various organic and inorganic constituents in tissue cells and plasma
are held in loose union by the bioplasm or proteins.

First, in regard to the carbohydrate material present in the
blood, it has been shown that if a stream of carbon-dioxide be
passed through a sample of blood, or if an anesthetic such as
chloroform or ether be added to it, and then it be subjected to
dialysis, the amount of sugar passing into the dialysate is con-
siderably increased, above the amount in the case of untreated
blood. It was at first supposed that this increased amount of
sugar came from the blood corpuscles, but more recent work has
demonstrated that there is practically no sugar present in the
corpuscles, and further a similar and equal increment in amount of
sugar dialysing out can be obtained when clear serum is used for
the experiment instead of whipped blood. If now a stream of air
be passed through the serum in order to remove the carbon-dioxide
or anesthetic before the serum is subjected to dialysis, it is found
that the yield of sugar in the dialysate has = back again to
the normal amount. : me .

\ ;

CRYSTALLOID IN LIVING CELLS 15

This experiment would appear to demonstrate that the sugar
in the serum exists in some form of feeble union with the protein
which the action of the mild acidity of the carbon-dioxide or the
residual affinity of the anesthetic is sufficient to break up, so
leaving the sugar free to dialyse out.

This union of carbohydrate and protein throws a light on the
glycosuria which follows hyperglycemia. For in hyperglycemia
there is an excess of sugar above that which can enter into union
with the protein, and it is this excess which is seized upon and
thrown out into the urine by the kidney cells. From this point
of view it is interesting to note that in the living animal, when
there is more than a certain percentage of carbon-dioxide in the
respired air for a given period, even though there be in the air
breathed more than the atmospheric proportion of oxygen, then
there invariably appears sugar in the urine in very considerable
amount. Also in the case of prolonged anesthesia, especially :if
the concentration of the anesthetic administered be increased to
the maximum limit, there always appears sugar in the urine, often
in high percentages. The author has found as much as 11 per
cent. of sugar in the urine of dogs after ether anesthesia, and
has shown that the reducing material present is undoubtedly
glucose by obtaining and separating typical glucosazone crystals
in abundance.

In the liver cells there is undoubtedly union between the
bioplasm and the sugar before glycogen is formed. The glycogen
up to a certain maximum limit at which it separates as granules
can also exist in union in the cell, for considerable amounts of
glycogen can be separated from the tissues long before separated
glycogen can be shown by histo-chemical methods.

Similar evidence has been obtained by different authors as
to the formation of unions -between cell proteins and fats. By
certain procedures, such as -partial interference with blood supply
(Bainbridge and Leathes), it has been possible to make the cells
of certain organs, notably those of the liver, take on the appear-
ances of fatty degeneration. The cells become loaded with obvious
fat globules, which stain with all the usual histo-chemical staining
reagents for fatty substances. It looks at first sight as if the
amount of fat in the organ had been enormously increased, but
the interesting point is that comparative analysis of normal
liver with no appearance of fat in the cells, and of such liver cells

2. «a
“te

,

16 THE EQUILIBRIUM OF COLLOID AND.

apparently loaded up with fat, demonstrate that the amounts of ~
fat in the two cases are about equal. !

The normal liver tissue is capable of holding 5 to 10 per cent.
of fat in such form that it is quite transparent and invisible
in discrete form, being in fact an integral part of the bioplasm.
This can be done in no other way than by some type of union, for
a fraction only of this fat in free condition would give a thick
emulsion, showing obvious globules under the microscope, as it
does when conditions are interfered with as above described, and
the feeble union of the fat with the tissue broken up.

Similar results are seen in the chemical phenomena accompany-
ing nerve degeneration. Again in the plasma or serum itself a
certain amount of union must take place, for, from a perfectly
clear serum, showing no oil globules whatever under the micro-
scope, as much as 0°5 to 1 per cent. of fat may be taken out by
organic extractives, such as alcohol and ether. Now this amount -
of fat, were there no agency to hold it in clear solution, would be
sufficient to give a white milky emulsion. It is only when the
capacity of the serum for holding fat in solution by feeble union
with proteins is surpassed that the milky serum often found after
a heavy fatty meal is obtainable, and this excess of fat is so soon
taken into union by the bioplasm of the liver and other tissue
cells, that in an hour or two no trace of any microscopically visible
fat is seen in the serum or elsewhere.

In this capacity of the serum for holding in union in invisible
form a certain amount of fat is found the solution of the problem
of fat transference in the body from one tissue to another without
any obvious carriage as an emulsion. By this power of solution
of fat in bioplasm is also provided the mechanism for the oxidation
of fats, for it is obvious that previously to oxidation the fat must
pass into simple molecular form, and that it cannot be oxidised as
globules of liquid fat.

Apart from direct oxidation to furnish energy for the cell’s
work, it is obvious that these lightly held unions of the organic
foodstuffs furnish the means for the chemical changes in the
cell which give rise to those syntheses of one organic body from
another which occur in animals as well as in plants; for the
synthesis of new proteins by the union of protein radicles rich in
amido-acids with carbohydrate radicles ; for the synthesis of fats
from carbohydrates; and for the elaboration of those products

-ORYSTALLOID IN LIVING CELLS 17

“of cell activity which we know as internal secretions, lysins, anti-
odies, toxins, hormones, &c.

Turning now from the organic foodstuffs and the synthesised
uets of metabolism to the inorganic crystalloids of the cells

oo body fluids, we find abundant evidence of union in labile

equilibrium between these and the organic constituents of the

body—unions which are absolutely essential to the life and work
of the cell, specific in character from one type of cell to another,
and which owe their peculiar and effective functional power in
the life of the cell to the very feebleness of the union which allows
_ of interchange and reaction. So that we have stability of the
whole system in the midst of and indeed as a consequence of the
instability of the constituent parts.

The first evidence which may be quoted in favour of this form
of union is the peculiar distribution of the inorganic salts and ions
as between tissue cells and their environing fluids, the plasma and
lymph.

Although the same inorganic salts are present in the cells
of the tissue and in the blood corpuscles as are found in
the lymph and plasma, the quantitative distribution is very
different in the two cases. The cells are rich in potassium and

_ phosphatic ions, and relatively poor in sodium and chlorides,
while the converse holds in the case of the bathing fluids of
the cells.

This peculiar distribution . finds an easy explanation on the
basis that the proteins of the cells are so constituted chemically
that they possess affinities for absorbing or uniting with potassium
and phosphatic ions, and have no such power for holding sodium
and chlorine, while the converse holds for the proteins of the plasma.
For under these conditions, with the same osmotic pressure of
dissolved constituents within and without the cell, any particular

ion will increase in amount in-the absorbed or united form in that

particular region where protein is found possessing an affinity
for it.

ar view which has obtained most adherence is that there exist

pranes with peculiar and specific properties surrounding the
which present a varying resistance to the passage of different
‘These membranes, which moogatly have been regarded as
B

No other view which has been put forward furnishes an ade- _
q quate explanation of this peculiar distribution of the salts. “The -

18 THE EQUILIBRIUM OF COLLOID AND ©

consisting of bodies called lipoids,’ related to the fats. hat
lecithins, are supposed to be easily permeable for some substances
such as urea, ammonia, carbonic-ions, and the anesthetics; but
difficultly or almost impermeable for other substances such as the
usual inorganic ions of the plasma, viz., potassium, sodium, phos-
phates and chlorides. As a result of this difficult permeability it
is supposed that the potassium is retained in the cell, and the
sodium in the plasma, while anesthetic, ammonia, and urea, for

example, rapidly pass through.” .

There are, however, fatal objections to this membrane view,
viz. first, that while it makes some attempt at an explanation of
the maintenance of the status quo, it fails entirely to explain how
that condition was originally arrived at; secondly, it inextricably
confuses factors which are of value in the velocity with which
equilibrium is arrived at with the final conditions of equilibrium ;
and thirdly, it fails to explain the phenomena of cell interchange
and the rapid physiological effects upon the cells of variations in
the concentration of the ions in the external medium.

If the cell is almost impermeable to potassium ions, for example,
it is difficult to see how it has become fully charged with them,
and to many times the amount that these are present in the nutrient
fluid outside.

Again, however poor the permeability, if there is no union -
between constituents within or without and the ion in question, it
is obvious that when equilibrium has finally been attained, the
concentrations at the two sides must be equal. Variations in
permeability can only alter the time required to reach equilibrium,
and not the final conditions of accumulation on the two sides
corresponding to the equilibrium.

Further, anesthesia cannot, as has been suggested by the
upholders of the membrane theory, arise from greater solubility
of the anesthetic in the membrane, because that would only delay

1 The text merely refers to lipoids regarded as semi-permeable membranes.
Using lipoid as a generic term to include the class of the lecithides and other forms
of compound fats, there is no doubt that these play an important réle in the life
of the cell by means of their power of éntering into combination or absorption with —
organic poisons and toxins. But this is entirely different from a membrane action, :
being a formation rather of easily dissociable unions of the kind shown in the text
to exist between bioplasm and organic bodies.

2 The questions of cell permeability, and the arguments for the membrat

view, may be found in detail in Hamburger’s Osmotischer Druck und Io
For the reasons given in the text they have not been stated at length.

_

the arrival of the anesthetic at the active part of the cell until
the lipoid membrane had first been saturated with anwsthetic.

_ For this reason also greater solubility of any constituent in
the cell substance itself will not explain the greater amount or
concentration of any particular substance or ion in the process
of secretion or excretion. Such greater solubility would serve to
‘fill the cell up with it and keep it there, but would not hasten passage
through the cell,and after the solubility in the cell substance had
been satisfied, diffusion would then go on until the free concentra-
tion on the secretion side equalled the concentration on the lymph
side, but not a fraction beyond this point.

With regard to increased or specific solubility in the cell sub-
stance as an agency in statically loading the cell up with a given
constituent or ion, as distinct from passing it out again in
heightened concentration in a secretion, it may be admitted that
this would explain the accumulation ; but this on closer examina-
tion is essentially the same view as that of union or adsorption
with the protein, except that the adsorption or combination view
goes a step further and attempts to give a basis for the increased
or specific solubility.

Even in the simpler case where a substance in solution divides
itself in different concentrations between two solvents which do
not mix with each other,’ giving rise to the quotient of distribution,

it is obvious that there is an equilibrium between the concentrations
_ in the two media depending upon the relative affinities (or residual
affinities) of the molecules of two solvents respectively for the
molecules of the solute or dissolved substance.

One may therefore quite justly assign the unequal distribution
of the various ions in cell and environing fluid respectively to
different solubilities in the two media; apart from membrane
action which is out of the question unless the somewhat absurd
hypothesis be made that the. accumulation remains and resides in
the membrane. But knowing the nature of the constitution of the
protein constituents, and that these must possess residual affinities
or absorptive powers, it appears feasible to go a step further and

w ons between protein or bioplasm and the ions.
On this view the cell of any tissue or the blood corpuscle is a
1 As, for example, an organic acid dividing itself between water and ethylic

~

ssign the distribution and different solubility to the fopenatigg of ~

20 THE EQUILIBRIUM OF COLLOID AND i

system in equilibrium regarding ions with its surrounding medium,
and the equilibrium is maintained by the pressure of each parti-
cular ion, acting independently, in the surrounding medium. Also
variations in concentration of any of the ions will cause reaction
and variation in the equilibrium of the whole, and may cause such
disturbances as will alter the distribution of other ions and soluble
substances, and so cause variations in the character and types of
reaction of the protein or bioplasm.

Two chief factors determine the equilibrium between each ion
and the cell; one of these is the concentration of the ion, the other
the constant of association or adsorption between the cell ‘sub-
stance and the ion. This constant changes its value specifically
from one ion to another with a constant type of cell or bioplasm ;
and with the same ion kept constant varies from type of cell to
type of cell, so giving rise to the specific picking out of particular
cell types by particular ions or other bodies."

In addition to these chief factors, there is some evidence that
certain ions can replace each other, or in other words compete for
the same vacant places in the protein or bioplasm. This is known
as the antagonistic action of drugs. Usually the ions so replacing
must be of the same order of valency, a monad being unable to
take the place of a dyad, but one dyad can replace another, and
especially two dyads in the same periodic group of elements are
interchangeable. For example, one heavy metal can take the
place of another, and even the paradox is arrived at that the
poisonous action of one of these heavy metals is decreased by the

1 This might be put in simple mathematical form thus: if C, be the concentra-
tion of the protein or other substratum in a given cell, Cy the concentration of
the ion to be absorbed in the medium outside (lymph), and Cs the concentration
of the substance adsorbed, then C3=KC,Co, where K is a constant dependent on
the chemical and physical affinities of ion or other substance for each other, and
hence having a different value when either ion or type of protein is changed. If
now we keep the same ion, as in the distribution of any naturally occurring ion
in the body, or in the action of any given drug which can only be given so that
it is free to act on all cells in the body, then for a different cell using small letters
we can write as before cs=kc,c, where the suffixes show the same meaning as

before. But now 2 and c, the concentration of the ion or drug in the circulating
medium is the sanie in both cells, and hence if we want to get the relative con-

centration in the two types of the cell we have out Pe and further if we take
3 1
it that the protein concentration is the same in the two cells, we finally have
\

oat or the relative distribution is in proportion to the affinities between ion or
3
drug and particular type of protein.

ve

’

CRYSTALLOID IN LIVING CELLS 21

simultaneous presence of another, so that instead of there being
an additive effect of the two poisons, one balances the other and
protects in part from its action, so that the lethal dose of either is
increased.

The ions of the inorganic salts at the same time that they are
in a loose type of union with the proteins, possess a freedom of
movement which shows itself in their giving to the solution in
which they exist in common with the colloidal proteins many of
| the more important physico-chemical properties of a saline solution.

For example, in the case of the blood serum, the depression of
freezing point is almost the same as that of an equal amount of
salts dissolved in distilled water, showing that here every ion in
the solution has its full effect in producing osmotic pressure not-

withstanding its adsorption by the serum proteins. Again, the
electrical conductivity is practically the same as that of an isosmotic
solution of the saline constituents alone in distilled water, showing
that any adsorption which may be present does not interfere in the
least with the movements or velocities of the ions in the electrical
field. Yet there is other evidence that the salts of the serum are
in union of some type with the proteins, and that the amount of
salts in the serum as regulated by the kidney cells is dependent
upon the combining power of the proteins.

One fact that gives a clear indication of this is the titration
value for the serum in presence of one of the more stable coloured
indicators, such as methyl orange or “‘di-methyl.” It has been
pointed out earlier in this article that the proteins can act either
as acids or bases, or as it is termed are amphoteric to indicators.
Thus, blood serum is acid to phenol-phthaléin, and must have
alkali added to it to produce the pink colour denoting alkalinity ;

at the same time it is alkaline to methyl orange or di-methyl, and
___ requires the addition of much acid before showing the acid colour
of the indicator.

The actual reaction of the serum is almost that of exact neutrality
in the sense of physical chemistry, that is to say, the concentrations
_ of hydrogen ion and hydroxy] ion are about equal. Now although
it is essential that the colour of an indicator for acid and alkali ~
should change before the ratio of the concentrations of the two —
ions becomes a high one, no indicator used in practice actually
does change exactly at the chemical or exact neutral point, and
the turning point is different for each one. Hence it is that blood

serum appears to be acid when tested by phenol-phthaléin, and
appears to be alkaline when tested by methyl orange, &c. Not,
as is too often stated, because it is at the same time acid and
alkaline, for that is absurd, but that its actual position in reaction
lies very nearly at the neutral point, and just short of that slight
degree of alkalinity which shows the alkaline colour to phenol-
phthaléin on the one hand, and just short of that degree of acidity
which gives the acid colour to methyl orange. Now these two.
points lie very close together, for if instead of the serum we take
distilled water and add the two indicators phenol-phthaléin and
methyl orange in traces to it, then a single drop of dilute alkali
will develop the alkaline colour of the phenol-phthaléin, and on
the other hand a single drop of dilute acid will show the acid colour
of the methyl orange.

In the case of the serum, however, the result is quite different,
for very considerable amounts of alkali must be added before it
turns alkaline to phenol-phthaléin, and proceeding in the opposite
direction still larger amounts of acid must be added before acidity
to methyl orange is realised. The reason for this is that the pro-
teins, which can figure either as acid or base according to whether
there is excess of alkali or acid respectively in the solution, must first
be satisfied before the indicators are affected ; and as the amount
of protein is large, so the amount of acid or alkali required before
it is neutralised and the acidity or alkalinity can commence rapidly
to run up and affect the coloured indicator, is very considerable.

This is a factor of great importance to the life of the cells, which
cannot bear any appreciable degree of either acidity or alkalinity,
and are protected from such variations by the very delicate regu-
lation of the reaction by the amphoteric proteins.

The regulating action of the proteins upon the reaction of the
serum has been mentioned here, however, because it gives a strong
indication that the proteins are in union with the inorganic salts.
If a clear sample of serum be titrated with methyl orange or “ di-
methyl” as.an indicator, an alkalinity equivalent to the very high
figure of 0:17. to 0°18 normal is obtained. This alkalinity is chiefly
due to proteins, for if the salts of the serum be separated off by
dialysis or incubation and titrated to the same indicator, the
alkalinity now ambunts to only 0:03 to 0:04 normal. Subtracting _
these amounts due to inorganic constituents from the higher figure,
we obtain the result that the combining power of the serum pro-

iii ae

22 THE EQUILIBRIUM OF COLLOID AND

CRYSTALLOID IN LIVING CELLS 23

teins alone for acid is equivalent to about 0°14 normal.’ Now
the interesting point about this figure is that it coincides almost
exactly with the total osmotic concentration of all the salts naturally
occurring in the serum or plasma. The depression of freezing
point of mammalian sera is on the average equivalent to that of a
0-9 per cent. solution of sodium chloride, and the molecular weight
of sodium chloride being 58, this corresponds to a 0°15 normal

: solution.

j In addition to this direct evidence from the chemical side,
there are certain physiological correspondences between amounts
of protein and crystalloid in the blood which must be obeyed, or
otherwise the excess of salt in the plasma is removed by the kidneys.
This action comes into operation as soon as the plasma salts exceed

- the amounts which can be loosely held by the proteins.

The salts in cells are held more firmly adsorbed or combined
than is the case in the plasma, as is shown by effects on the elec-
trical conductivity and by the difficulty of dialysing the salts
from the cells.

Thus it is found that although the osmotic concentration of
the salts in the red blood corpuscles is nearly the same as in the
plasma, as shown by the depressions of freezing points,’ yet the
electrical conductivity of the separated corpuscles is only one-
fourteenth to one-seventeenth of that of the separated serum.
Part of this difference is mechanical and due to the envelopes of
the corpuscles rendering the conducting fluid non-homogeneous ;
but even after removing this factor by laking, the conductivity of
the laked corpuscles still remains only at one-fifth to one-sixth of
that of the serum. This difference is undoubtedly due to the
attachment of the ions to the hemoglobin interfering with the
ionic velocities, for on dialysing, against distilled water and then
reducing the volume of the dialysate to such a degree as to re-
present the original concentration of the salts before dialysis, it is
found that the conductivity of the free salts in the dialysate has
undergone a further increase above that which they possessed
when in union with the hemoglobin, and now lies at about one-
half the value in the serum. Even dialysis, however, is unable.
to detach the phosphates from the hemoglobin, and the above

————y)~—tf
>

1 The amount of this combining power of the protein may be better appreciated
by some if it be stated as equivalent to about 0°51 per cent. of hydrochloric acid.

2 Vide infra.

a

24 THE EQUILIBRIUM OF COLLOID AND

conductivity of one-half is chiefly due to chlorides detached in
the process of dialysis. It is only after incineration and making
up to original volume that the conductivities of corpuscles and
serum become practically equal.

The following table illustrates these interesting changes in
conductivity accompanying detachment of colloid and crystalloid
in two experiments on separated blood corpuscles and serum.
The figures give specific conductivity multiplied by 10° to save
decimals.

-

SAMPLE I. SAMPLE II.
Treatment to which subjected. Serum. Corpuscles. Serum. Corpuscles.
1. Fresh . : $ : - 1705 95 1519 109
2. Frozen solid and thawed? ,,,5 ,
(corpuscles laked) . mA ma ae — asf .
3. Dialysed and volume re- id 1843 89] 1623 754
duced to original j <\
4. Incinerated and ash made) 1608 1677 1697 1655
up to original volume 5

That the phosphates are more firmly held than the chlorides,
so that the union persists even in presence of a very low concen-
tration of phosphatic ions in the fluid, is shown by the following
analysis for chlorides and phosphates in the dialysates of corpuscles
and serum respectively, and in the two cases after incineration.
The figures also illustrate the very different distribution of chlorides
and phosphates in corpuscles and serum respectively.

Serum Percentages. Corpuscle Percentages.
Cl, P50... Cl. P,0,.
Dialysis . : . 03657 0°:0197 01331 0:0329
Incineration . . 0°3373 00219 0:1704 0°1708

Even the chlorides are more strongly held in corpuscles than in
serum, the figure on incineration being considerably higher than
after dialysis, 0°1704 as against 0°1331, instead of being slightly
lower, due to volatilisation with organic matter, as in the case of
the serum, 0:3373 as against 0°3657. In the serum the phosphate
figures are almost equal by the two methods, but in the corpuscles
the evidence of union is clear, only 0:0329 per cent. dialyses out of
the 0°1708 shown to be present by incineration. These figures are
completely confirmed by freezing point determinations.

This experimental evidence is interesting as showing that the
special affinities existing in each case between protein and ion

-—

Tegel

CRYSTALLOID IN LIVING CELLS 25

demand very different pressures or concentrations to preserve
_ the equilibrium.

We can now understand why so little phosphate is required in
the Ringer’s solution; the union of the phosphates is so strong
that it is not possible to run the phosphate concentration down to
such a level as rapidly to disintegrate the phosphatic ions of the
cardiac tissue. The merest trace given off from the heart to the
perfusing fluid suffices to stop further loss. The level for calcium
and potassium, though low, is somewhat higher, and traces sufficient
to preserve equilibrium must be added, or these ions break free from
the cardiac cells, producing irregularity of function. Finally, the
sodium and chlorine ions are but loosely held, and hence as much as
0-7 to 0°9 per cent. of sodium chloride must be present to preserve
the equilibrium and normal conditions of physiological activity.

The facts as to the constitution of the colloidal material and
its relationship with electrolytes and other crystalloids which have
been given above, and the interpretation put upon those facts,
are intended to demonstrate that the living cell is a peculiarly
constructed energy machine or energy transformer, dependent for
its activity upon a delicate labile equilibrium giving stability as
a whole, and yet a weakness of union causing disruption and
. oxidation of parts, and so furnishing energy. The view put forward

is intended as a reaction from that view which complacently re-
gards all the work of the cell and peculiarity in its constitution
as being due to the physical properties of inert membranes.

The attempt has been made’to show that something is required
more than membranes and osmotic pressure to explain the peculiar
distribution of electrolytes in cell and nutrient medium, and going
further to give a basis for the understanding of the peculiar energy
exchanges of cells. It has been sought to invoke the peculiar
chemical constitution of protein and bioplasm, and the varying
equilibria of these with the materials brought in from the nutrient
media at varying pressures, giving rise to transient stages of
association and dissociation, and an accompanying play of energy

/ changes.

} It is not intended in doing this, however, to suggest that mem-
branes and variations in osmotic pressure play no part in the cell’s
work or in preserving the integrity of the cell, nor to depreciate
work upon osmotic conditions in cell life. Because there are other
factors to be reckoned with, it does not follow that osmosis is to

be neglected. In fact a wider appreciation of the phenomena of
union between the bioplasm and crystalloid constituents widens
rather than narrows our conceptions of the cell as an osmotic
centre, by allowing us to regard the cell as a chamber with vary-
ing osmotic properties, both of contents and wall, rather than as
heretofore as a-more or less fixed solution, bounded by a mem-
brane of fixed properties also, and resembling a semi-permeable
copper-ferrocyanide wall.

The rigorous conception of the cell as analogous in all respects
to a fluid medium holding crystalloids simply in solution and
bounded by a semi-permeable wall is most pernicious in biology,
for there are no experimental facts to warrant such a view, but
rather, as has been shown above, quite the reverse.

The whole chemical structure of the cell and that part of it
which is physiologically active 7s the osmotic machine, and needs
no membrane permeable or impermeable in order to exhibit the’
usual osmotic phenomena of shrinking or swelling, leading finally
to disruption. In some cases membranes in the narrower sense
of the word are demonstrable surrounding the cell mass, and in
other cases which form the vast majority, no such coarsely structural
membranes exist ; but in all cases the nature of the bioplasm is
so differentiated chemically as to form a dividing surface readily
permeable to the solvent, and this is all that is required, in addition
to the varying unions or holding powers between the cell colloids
and crystalloids, to establish an osmotic cell. As an example of
what is meant here we may instance the swelling of fibrin, con-
nective tissue, and gelatine under the imbibition of water. Be-
tween gelatine and water there is no. structural membrane with
semi-permeable pores, yet the gelatine takes.in water in a truly
osmotic fashion, and the pressure developed, if the swelling and
uptake of water are resisted, is very high.

It is hence necessary to get our minds rid of the preconceived
idea derived from too closely drawn analogies with experimentally ©
constructed osmotic cells that the cell membrane is responsible
for the osmotic behaviour of the whole cell.

If instead of this we take the view, which is supported by ex-
perimental facts, that the bioplasm) holds the crystalloids in loose
union in the cell, so that they cannot for the time escape or diffuse =
out, and yet admits of a degree of molecular freedom to the
crystalloids, so that they still attract water molecules by residual

- ‘
se at —~ P.

26 THE EQUILIBRIUM OF COLLOID AND

CRYSTALLOID IN LIVING CELLS 27

_ affinity, then we arrive at a conception which is capable of linking
together the osmotic properties of the cell, not merely in a statical
but in a dynamic way, and gives a basis for understanding the
variations in osmotic effects which accompany cell activities from
one phase to another.

With the view of an inert semi-permeable membrane of fixed
_ properties, not sharing the varying changes in chemical constitu-
tion associated with life, or in other words not possessing the
properties of bioplasm outlined above, all that can be arrived at
is a continual tendency in one direction to a fixed equilibrium.

The other view, that the osmotic properties are developed by
the bioplasm itself in its varying unions with crystalloids, gives
room for that up and down play of properties which is the out-
standing characteristic of living matter.’

For example, a circulating hormone, a drug substance or a
| nerve impulse arriving at a given set of cells in a tissue, may activate

the cells by momentarily disrupting unions between bioplasm and
crystalloids or the reverse, and so may cause an uptake or a giving
out of water accompanied by certain crystalloids free in excess to
or from the cell, or may alter water distribution in varying parts
provoking muscular contraction or other form of protoplasmic
movement.

Similarly molecular movements -of radicles attached to the
bioplasm may be induced, causing changes in molecular arrange-
ment and synthesis of new bodies within the cell. Further, the
osmotic pressures and concentrations of the crystalloids and other
bodies so set free need obviously bear no immediate relationship
to the concentration of these substances in the plasma outside the
cell, and so the very varying concentrations of secretions may be
understood in a way that cannot be realised on any basis of pure
osmosis or filtration.

The experimental facts of cell life, both in regard to the taking
up and giving out water and substances in solution, furnish a
clear demonstration that neither osmosis nor any other physical

_ hypothesis which leaves out the peculiar and varying chemical

secretion, or excretion.

1 It is interesting to note that serum proteins exactly at their neutral point

show no osmotic pressure whatever, but addition of minute amounts either of acid

or alkali at once gives rise to an osmotic pressure which up to certain limits
increases with amount of acid or alkali added. ~

constitution of bioplasm can yield an explanation of absorption, - _

28 THE EQUILIBRIUM OF COLLOID AND i

The whole of the experiments lend support to the view that
the living cell exists in a periodically or phasically varying osmotic
equilibrium with its surroundings, and not in a state of osmotic
equality with them. The cell by its unions with crystalloids pre-
serves a distinct osmotic condition within its bounds different
from that in the surrounding fluid media from which its nutrient
materials are taken up. This is particularly well seen when the
medium without is subject to considerable and accidental varia-
tions. Even in those cases where the outer medium is practically
constant, as in the extreme case, for example, of blood corpuscle
and plasma, although there appears to be an existence of osmotic
equality within the cell, and without, yet this is due to the peculiar
conditions having induced a close coincidence of the two sets of
osmotic phenomena, and the existence of an equilibrium and not
an equality may be easily shown by suitably varying the condi-

tions. So that even in these extreme cases what we have to do -

with is not really equality of osmotic pressures, but an equilibrium
which happens to simulate equality from the presence of reducing
conditions; the equality disappears as soon as these reducing
conditions are disturbed.

When the corpuscles of whipped blood are separated as com-
pletely as possible from the serum by means of the centrifuge,
and the depressions of freezing point of the corpuscles and of
the serum separately determined, it is found that the freezing
point of the serum lies on the average at 0:02° to 0:03° C. lower
than that of the corpuscles. This difference, small as it is, is con-
stant in its occurrence, and corresponds to a difference in osmotic
pressure of approximately 200 to 300 m.m. of mercury. If the
corpuscles after separation from the serum are thoroughly shaken
up with saline solutions weaker and stronger than the serum, or
as they are termed, hypo- and hyper-tonic solutions, it is always
found, on again separating corpuscles and saline by means of the
centrifuge, that the depression of the freezing point of the saline
is greater than that of the corpuscles, no matter whether the saline
employed was hypotonic or hypertonic. The differences become
in these cases much greater than the natural differences between
corpuscles and serum. These results show that there is established,
as the concentration of the saline is varied, an equilibrium for
each strength of saline, but not an equality, there always being a
negative osmotic difference within the corpuscle.

fi

CRYSTALLOID IN LIVING CELLS 29

In other types of cell these differences in osmotic pressure
within and without the cell become enormously greater. Thus,
in plants, the root sap which carries up the electrolytes from the
earth for the nutrition of the growing cells is exceedingly dilute,
the depression of freezing point being only about one-fifth part
of that of the cell juice. Similarly, in the secretion of sweat and
_ galiva the concentration of inorganic ions, as shown both by freezing
point methods and by direct chemical analyses, is only a small
fraction of that of the plasma or lymph. In other cases, such
as absorption by the intestinal cells and secretion by the kidney
cells, the osmotic pressure on the side remote from the lymph may
lie either above or below that on the lymph side, but nearly always
differs widely from it. It has been shown that either distilled
water or hypertonic salines can be taken up by the intact intestinal
mucosa; and the A (i.e. freezing-point depression) of the urine
may be many times greater than that of the plasma, or may
after ingestion or intra-venous injection of much water be a mere
fraction of the A of the plasma.
Whether the tremendous pressure differences corresponding to
_ these differences in A really exist within the cells must remain
indeterminate so long as we possess no knowledge as to the degree
to which the crystalloids of the secretion are adsorbed while the
secretion is passing through the cell and is in contact with the
bioplasm. By alternating or periodic dissociation and combina-
tion between colloid and crystalloid in the actively secreting (ab-
sorbing or excreting) cell, the pressures would appear and disappear
alternately ; and if by the action of, the nerve supply or any stimu-
lating substance the bioplasm is thrown into any such rhythmic
activity of adsorption and re-separation, there would follow an
easy explanation of the passage of both water and crystalloid
through cells, in any concentration. For the concentration would
depend solely on the uptake of crystalloid by the cell colloid, before
the next explosion, disrupting colloid and crystalloid, threw the
crystalloid free in the cell and determined, by the osmotic pressure
_ developed: thereby in the cell, the flow of secretion.

It would appear that in nerve and muscle at the period of
activity only, and in injured tissue (which is excited or active
tissue), there exists in reality a detachment of potassium ions from
the colloid which does not exist before or after the active period
penal :

}

30 THE EQUILIBRIUM OF COLLOID AND on |

’

It has been already pointed out that for each constituent
passing into union with the bioplasm there exists an optimum
concentration or osmotic pressure of solution in the nutrient
medium of the cell which alone is compatible with normal physio-
logical activity ; or rather it might better be put that there is a
range of suitable concentrations with a minimum and maximum
which must not be passed in either direction.

This point is particularly well illustrated in the case of the
respiratory gases. For both oxygen and carbon-dioxide there are
well-marked limits of pressure which are required to be satisfied
in order that the processes of respiration and oxidation in the
tissues may proceed in a normal fashion.

Since the energy for all tissue activity is derived from the
oxidation of organic bodies it is obvious that there must be a
minimal pressure of oxygen below which life is impossible, but it
is not so obvious that there is an upper limit of oxygen concen- °
tration at which life becomes equally impossible. Yet it is found
that when warm-blooded animals are exposed to a pressure of
about three atmospheres of pure oxygen, death occurs in a few
minutes after violent convulsions (Bert). Short of this excessive
pressure, exposure to over one atmosphere of pure oxygen for a
longer period leads, as shown by Lorrain Smith and L. Hill, toa
pheumonic condition of the lungs.

If pure oxygen at atmospheric pressure be breathed for a
shorter time interval, the tissues become charged with oxygen at a
higher pressure than normal, and Hill and Flack have shown that
for a short period afterwards muscular work can be done at a
more rapid rate in such forms of exercise as sprinting, hill-climbing,
and working against resistance. After exhaustive muscular exer-
tion also the breathing of oxygen diminishes the dyspnea and
sense of fatigue.

On proceeding in the direction of testing the effects of per-
centages of oxygen less than the atmospheric, it is found that the
results obtained depend upon the type of mammal experimented
with, and upon the state of quiescence or activity of the animal.
As the percentage of oxygen decreases the will and energy to do
work diminish, and at a partial pressure of about half that present
in the atmosphere any attempt at muscular work has to be aban-
doned, and the mental processes also become most sluggish.

The earlier experiments on the absolute minimum amounts of

CRYSTALLOID IN LIVING CELLS 31

_ oxygen required to support life in animals in a state of quiescence
were vitiated by the simultaneous accumulation of carbon-dioxide
from the respiration of the animals.

When means are taken to exclude this source of error by ab-

_ sorbing the carbon-dioxide with soda-lime as rapidly as it is formed,

it is found that animals (rabbits) can be kept alive for as long as
forty hours on a respiratory mixture containing as little as 5 to
6 per cent. of oxygen. With slightly less than 5 per cent. of oxygen,
death occurs very rapidly. .

These results, considered together, show that there is a mini-
mum concentration of oxygen necessary for sufficient oxidation to
support life ; that as the pressure rises the degree of combination
or union between bioplasm and oxygen increases, quickening the
oxidation processes in the tissues; that an optimum of activity
exists somewhere above the normal amount present in atmos-
pheric air; and that still higher up embarrassment occurs from
too high pressure, causing firmer union between the oxygen and
bioplasm.

A very parallel set of results are obtained in the case of carbon-
dioxide. Here it might be thought that since carbon-dioxide is
a waste product of the oxidation process, the best possible con-
dition would be its complete removal; but it has been clearly
shown by Haldane that a definite minimal percentage of carbon-
dioxide is required for the regulation of the respiratory exchange,
and that when the percentage is reduced by artificial ventilation,
the subject passes into apnoea or suspension of breathing until
the amount is brought back towatds normal in the lungs and
tissues. The normal amount of carbon-dioxide in the alveolar
spaces lies between 4 and 5 per cent., and if it rises or falls but
slightly from the normal, corresponding changes take place in the
respiratory rhythm and depth which tend to restore the balance

once more.

| It has further been shown by Henderson that excessive and
prolonged ventilation of the lungs by artificial means leads by

lowering of the carbon-dioxide concentration to irregularity of the

heart beat, and finally, if pushed, to delirium cordis and death of

the animal. Short of this limit, stoppage of the positive ventila-

tion has the effect of restoring the heart to regular rhythm.

__ Passing in the opposite direction, and observing the effects of

_ increasing amounts of carbon-dioxide, administered in artificial

7

32 THE EQUILIBRIUM OF COLLOID AND

mixtures containing as high, or higher, amounts of oxygen as are

present in atmospheric air so as to avoid asphyxiation from de-
ficiency of oxygen, it is found that carbon-dioxide has directly
poisonous effects upon the bioplasm. Thus, with 12 to 15 per cent.
of carbon-dioxide and 20 to 25 per cent. of oxygen, it is, found
that animals become somnolent, and, as above stated, that the
urine contains glucose, while with 20 to 25 per cent. of carbon-
dioxide, even in presence of excess of oxygen, death rapidly occurs.

The same effects are seen upon isolated tissues. Thus Waller
has shown that the first effects of minimal traces of carbon-dioxide
is to increase the excitability of nerve, while larger doses diminish
excitability, and finally all excitability disappears. Similar results
are found in unicellular organisms and in ciliary movements.

All these results point to varying degrees of union and corre-
sponding stability or instability of union between carbon-dioxide
and bioplasm.

Exactly similar results are everywhere evident in the applica-
tion of various drugs in therapeutics, in the action of the toxins
of disease, and in the action of antiseptics. There is the same
stimulating action seen, followed by paralysing action as the con-
centration is increased and the union between bioplasm and drug
becomes more stable and complete.

One of the most striking results here is the adaptation between
drug and different types of cell, due to molecular variations in
the structure of the two reacting bodies causing them to possess
higher affinities. and unite at lower concentrations. For this
reason one type of cell takes up a drug and robs the other cells
of it, lowering the pressure in these other cells and the plasma,
so that the particular type of cell becomes loaded up at a pressure
which scarcely causes any uptake in other cells.

On such a basis it is easy to understand why all mercury salts
produce the same specific action in syphilis, the result being due
to the free mercury ion and not being affected by the anion of
the salt used except in so far as this quantitatively alters the
degree of ionisation, and hence the concentration of mercury ion.
Similarly, the ferric ion in all iron salts stimulates the production
of erythrocytes in anzmia. So too quinine, and the alkaloids
generally, furnish a basic ion affecting specific cells of the organism
in each case, or of pathogenic foreign organisms present in it, for
which at different stages they possess special affinities.

-CRYSTALLOID IN LIVING CELLS 33

_ The same specific action due to different detail in structure of
biopls sm, which we see exemplified in the picking out action of
‘drugs in the multicellular organism, is seen, and from the same
cause, in the action of different drugs upon different stages of the
‘same parasitic organism.

For example, quinine only attacks the malarial parasite when
it is breaking forth from the erythrocyte. Again, the drug atoxyl
acts on the ordinary motile form of the trypanosome, but rapid
recurrence shows that it does not destroy the latent bodies, while
mercury is shown, by the prolongation in the period of recurrence
which it causes when given after atoxyl, to attack the latent bodies,
although it has no action whatever on the ordinary motile stage.

The closer and more detailed study of the conditions of the
formation of these unstable unions between bioplasm and the
dissolved substances of its natural and artificially varied environ-

ment must furnish the key to many of the intricate problems both
of physiology and of practical medicine ; and it may perhaps be
added that these subjects, whether studied in the laboratory or
by the bedside, form one organic whole, for the subject of study
in both is the living cell in all its wealth of reaction to changes in
its environment.

THE HEART
By MARTIN FLACK

From time immemorial the heart has been the object of great,
although perhaps not altogether scientific interest. In recent
years many points relating to its anatomy and physiology have
occupied the attention of investigators, so that the literature upon
these subjects has become very large and in many respects in-
tricate. In the following remarks the subject will be treated
under these headings :—

A. The microscopic anatomy of the heart.

B. The morphology of the vertebrate heart.

C. The nervous elements of the vertebrate heart.

D. The heart as a muscle.

E. The site of origin and mode of conduction of the excitatory
wave of the heart.

F. The movements of the heart in situ.

A. THE Microscopic ANATOMY OF THE HEART

The heart musculature must not be regarded as being built up
of a number of separate cells fixed together by a cement sub-
stance. It is really a network of cells, intimately fused on all sides,
or as it is sometimes termed a syncytium (Kolliker, M. Heidenhain).

In fresh and in well-prepared fixed preparations there is no
trace of division of the musculature into short mononuclear seg-
ments or cells. The muscle fibre is seen to pass many nuclei
without the appearance of a division or cement line between them
—indeed in the heart of mammals such small segmented portions
are hard to find, and seem only to occur in the circular bands of
muscle at the heart orifices and in the musculi papillares.

According to M. Heidenhain, the muscle fibres of the heart are
about one-third thinner in diameter than those of voluntary
muscle. They possess nuclei, sarcoplasm, fibrillary substance, and

34

THE HEART 35

sarcolemma. The nuclei lie at regular intervals inside the fibre ;
they are elliptical in shape, 7-16 « long, 5-9 « broad, and possess
a well-marked chromatin network and a nucleolus. At both poles
of the nucleus is situated a mass of granular protoplasm, the
sarcoplasm. This sarcoplasm is more richly developed than
in voluntary muscle, and contains strongly refractile basophile
granules which in the adult are frequently yellow or yellow brown.
Their presence, so far as is known, denotes nothing abnormal.
Running out from the central sarcoplasm between the bundles
of fibrils to the periphery of the fibre there is a very delicate proto-
plasmic membrane, the sarcolemma, often richly impregnated with
+ fine granules. It is perhaps not so well developed as in striated
muscle, and differs in not being of a chitinous nature.

The contractile substance of the heart muscle fibre is made up
of a number of bundles of fibrils, the sarcostyles. These are some-
what prismatic in shape, and lie at the periphery of the fibre ; the
centre being occupied by the nucleus and the sarcoplasm (Kolliker).
The sarcostyles exhibit longitudinal and frequently transverse
striation ; the former being due to its composition of fibrils ; the
latter to the presence of singly and doubly refractile substances
within the fibril. When the sarcolemma running between the
fibrils is well marked, the transverse striation is masked.

There is an intimate fusion between neighbouring fibres—a
number of fibrils from:one fibre becoming detached and passing
uninterruptedly into its neighbour. From this it will be seen
that only the small amount of protoplasm situated around the
various nuclei can be looked upon as being discontinuous and in
any way comparable to the original cells (the myoblasts) from

_ which the heart is developed. These cells appear to have be-
come fused together to form a syncytium, and in this a common
network of fibrils has been laid down.

The question then arises that, if the lines formerly described

by von Eberth as separating the cells of cardiac muscle from
_ each other, do nothing of the kind, what is their function? Von
_ Eberth thought they were a cement substance binding the cells
together, and called them “cement lines” in consequence. This
view: ‘has been given up. The lines do not separate cells since the
fibrils pass through them (v. Przewosky, v. Ebner, M. Heidenhain).
Th many places, too, it can be seen, particularly in a fresh prepara-
ion that the so-called line does not always go completely across

| MMR +.
1

yale rn

oe

36 THE HEART

a fibre—it may only go part of the way across, or it may go
across in step-like fashion.

According to v. Ebner these lines represent a dying phenoménon
—a thickening of the fibre due to an abnormal contraction
during death. Eppinger regards them as pathological in origin.
M. Heidenhain, on the other hand, believes that they are really
present in the normal fibre, and have a special function to per-
form in regulating the growth of the fibre. He therefore terms
them “ Schaltstiicke ” (“regulators”). In the human heart they
are 1-1-7 uw thick, and consist of separate parallel perpendicular
rods. As we have said, they do not necessarily go right across a
fibre. The intervals at which they occur are by no means regular :
the pieces shut off by them may be of any length, and cannot be
looked upon in any way as cells.

To sum up, the heart muscle, according to the more recent
investigations, is to be regarded as a syncytium in which a common ~
network of fibres has been developed.

B. Tue MorpeuHoLoGy oF THE VERTEBRATE HEART

The study of the comparative anatomy of the vertebrate heart
greatly facilitates a proper understanding of the most recent
anatomical work on the mammalian heart—namely, the isolation
of the auriculo-ventricular bundle. It aids us also in estimating
the significance of the many facts known about the heart, and
also in arriving at the probable value of the theories held in
regard to its working. Furthermore, the study of the comparative
anatomy is undoubtedly very helpful in bringing out points about
which research is still required and also in determining the lines
of such research.

The Primitive Vertebrate Heart.—Figure | is a generalised
diagram of sucha heart. It consists of five chambers—(a) The sinus
venosus ; (b) the auricular canal; (c) the auricle ; (d) the ventricle ;
(e) the bulbus cordis. These parts are all in free muscular con-
tinuity ; there is no break at any of the junctional lines (1.1, 2.2,
4.4, 5, in Fig. 1).

This is a point of interest, since in tracing the representatives
of these primary divisions in the mammalian, and especially in —
the human, heart, it will be of service to ascertain whether this |
muscular continuity between the different chambers still exists, 3

THE HEART 37

The Sinus Venosus in the Human Heart.—The sinus venosus
is of importance in primitive vertebrate hearts, because it is here
that many authorities have observed the origin of the heart rhythm
(Gaskell, MacWilliam, Engelmann). This fact makes it essential
for us to know what parts represent the sinus venosus in the

Fic. 1.—A generalised type of vertebrate heart—combining features found in
the eel, dogfish, and frog (Keith) ; @, sinus venosus and veins; }, auricular canal ;
¢, auricle; d, ventricle; ¢, bulbus cordis; /, aorta; 1-1, sino-auricular junction
and venous valves; 2-2, canalo-auricular junction ; 3-3, annular part of auricle ;
4—4, invaginated part of auricle ; 5, bulbo-ventricular junction.

mammalian heart, since in them one might expect the heart
rhythm to arise.

The sinus venosus is represented in the mammalian heart by
four remnants :—(1) The termination of the superior vena cava
(the right duct of Cuvier). (2) The coronary sinus (the left duct
of Cuvier), (3) A stratum submerged beneath auricular tissue at
the tenia terminalis. (4) The remnants of the venous valves,
i.e. the Thebesian and Eustachian valves.

This does not represent a large amount of tissue, and it is diffi-
cult to trace in the mammalian heart. I would, however, draw
attention to the occurrence in all mammalian hearts examined
of a remarkable remnant of primitive fibres persisting at the sino-

' - "ee BR Soy
cad . a oe
(ee

38 THE HEART E

auricular junction—that is, where the superior vena cava joins the
tenia terminalis of the right auricle (beneath a, Fig. 4). This corre-
sponds in position to the right venous valve of the sinus venosus
of the primitive heart. The remnant has been termed the “ sino-
auricular node.” It is interesting because it is in close muscular
connection (1) with the outer wall of the auricle; (2) with the
interauricular septum. In the latter fibres pass from the node
down the septum to another remnant of primitive fibres at the
base of the septum known as the auriculo-ventricular or A-V
node. To this we shall refer again, but it is worthy of note that
the two nodes, identical in structure, and therefore probably in
function, are in muscular connection with each other.

The sino-auricular node has a special blood supply, and the
nerves in the neighbourhood come into intimate relationship with
it (Keith and Flack).

The Auricular Canal of the Human Heart.—It will beseen |
that in the simple form of vertebrate heart (Fig. 1) the auricular
canal consists of three parts :—

(1) A basal part opposite the auricle.

(2) An annular part or “auricular ring ” (3.3).

(3) An invaginated or intraventricular part (4.4).

The basal part is the ventral wall of the primitive cardiac tube.
The auricle (c) has developed from the dorsal wall alone, leaving
the ventral wall unspecialised. The basal wall is therefore con-
tinuous with—

(a) The sinus venosus.

(b) With the ostium of the auricle.

(c) With the auricular ring.

Does this continuity persist in the mammalian heart? In this
heart the basal wall has become profoundly modified owing to
the formation of an interauricular septum and a vestibule to the
left auricle. Both these structures have been developed from
the primitive basal wall.

The “auricular ring” is that portion of the auricular canal
interposed between the auricle and the ventricle (3.3, Fig. 1),-and
in these hearts is of comparatively appreciable dimensions. In
the mammalian heart, however, it is represented by a small
but nevertheless important’remnant. This is submerged in the
- auriculo-ventricular groove at the junction of the auricles and
ventricles. The shape of “the ring,” however, has become

é

modified owing to the extension of the bases of the ventricles
backwards under the basal wall of the auricular canal. By this
means the mesial fold has come to rest at the base of the inter-
auricular septum on the right side just about the top of the inter-
ventricular septum. Most of the fibres representing the auricular
part have become indistinguishable from the other auricular
tissue, but the circular fibres of the auriculo-ventricular groove
may be held to represent them. However at the spot referred
to above, namely, at the base of the interauricular septum on the
right side, a portion of the ring has remained undifferentiated. This
is the node of tissue termed the “ auriculo-ventricular or A-V node,”
and which is similar in structure to the “ sino-auricular node.”

The invaginated portion of the auricular canal is of interest,
since in the lower type of heart (Fig. 1, 4.4) it forms a muscular
connection between the auricular and ventricular portions of
the heart. Has this invaginated portion any homologue in the
mammalian heart, since if it have then a muscular connection
must exist between the auricles and ventricles of the mammalian
heart ? For a long time this question was answered in the negative.
The anatomists taught that in the mammalian heart the auricles
were absolutely separated from the ventricles by fibrous tissue,
so that no such muscular connection could exist. In 1893, how-
ever, His, jun., described a muscular connection between the
auricles and ventricles. Stanley Kent also in the same year
came to the conclusion that the auricle and ventricle were con-
nected by muscle. Recently in 1904 Retzer and also Briiunig
corroborated the observation of His in certain mammalian hearts,
but not in all. Tawara in 1905 published a most elaborate and
accurate account of this muscular connection, its extensive nature
and its connection with the Purkinje fibres. Both he and other
observers have found it in all the mammalian hearts examined,
so that now there appears to be no doubt that such a muscular
connection exists in all mammalian hearts. Keith and the writer
have shown that, as might be expected, it is the homologue of the
invaginated portion of the auricular ring. As later we shall have

well to describe it in some detail.

_ The Muscular Connection between Auricle and Ven-
tricle in the Mammalian Heart. The Auriculo-Ventricular

.

THE HEART 39°

occasion to refer to this muscular connection, it will perhaps be -

V) Bundle.—This connection is sometimes called after His,

Sh

40 THE HEART

who first described it, the bundle of His; but it is perhaps simpler
to term it the auriculo-ventricular or A-V bundle. The bundle,
as first shown by Tawara, consists of four portions :—

(1) The auriculo-ventricular or A-V node.

(2) The main bundle.

(3) The septal divisions, right and left.

(4) The terminal ramifications.

These divisions can be followed in some hearts better than in others ;
for instance in the hearts of the sheep and ox it is a matter of great
ease, since the fibres constituting the bundle are much paler than
those of the surrounding musculature, and therefore easier to dissect
out. These hearts, therefore, are recommended for preliminary
dissections of the bundle. Microscopically also the fibres of the
bundle present a greater contrast to the rest of the musculature in
these hearts, so that the course and structure of the bundle are
more easily followed through a series of sections, a matter of con-
siderable difficulty at first in the human heart where the fibres
are less differentiated.

Taking the human heart, however, as a type, it may be said
that the auriculo-ventricular node lies, as described above, at the
base of the interauricular septum on the right side (3, Fig. 2). It
is in close connection (1) with the fibres of the interauricular septum
and thus indirectly with the sino-auricular node; (2) with the
right auricle proper by means of the circular fibres of the A-V
groove. A good guide to its position is the coronary sinus (8,
Fig. 2). The node lies below and to the right.

Arising from the A-V node is the main bundle (2, Fig. 2).
This rides along the top of the interventricular septum below
the pars membraneza septi—a spot easily found in the human
heart by holding the organ up to the light. The knife may be
safely entered through this spot, and the isolation of the bundle
thereby facilitated. At this point the main bundle divides into
its right and left septal divisions (Fig. 2). These divisions turn
downwards. on the interventricular septum, and make for the
septal groups of musculi papillares. On the right side the
division is in the form of a fairly fine cord, and may run part
of its course embedded in the tissue of the septum; but it
usually becomes superficial as it approaches the septal group of
musculi papillares, and it can be invariably found in that position
' (Fig. 2, 4). On the left side close inspection of the septum will

a

THE HEART 41

reveal this division of the bundle as a delicate flattened ribbon
of fibres passing downward directly beneath the endocardium.
The ribbon soon breaks up into smaller strands which pass to the
musculi papillares situated on the septum (4, 6, Fig. 3).

Arising from the groups of musculi papillares in either chamber
are the terminal ramifications of the bundle. They frequently,
especially on the right side, take the form of small moderator
bands, and pass out to all parts of the ventricular wall. Here

Fic. 2.—Right auricle and ventricle of calf (Keith). 1, Central cartilage ;
2, main bundle; 3, A-V node; 4, right septal division; 5, moderator band;
8, orifice of coronary sinus.

they can be seen as delicate trabecule passing from one part to

another. Eventually they fuse with the ventricular musculature.

With regard to the microscopic appearances of the various
parts of the bundle, Tawara in his book gives drawings of them for
the sheep’s heart. In such hearts they are quite easy to recognise.
The chief points to be noted are—(1) The peculiar branched cells of
the A-V node. (2) The large pale cells of the main bundle with
their large nuclei. (3) The peculiar Purkinje cells found in the
septal divisions, and their terminal ramifications (especially in a so-

called moderator band).

42 THE HEART

In the human heart the different portions of the bundle are not
so easy to recognise microscopically. With a little practice, however,
the bundle can be traced through a series of sections in its course

Fic, 3.—Left ventricle of calf (Keith). 1, Left septal division of A-V bundle ;
2, 3, subaortic musculature divided to show passage of bundle from right side of
heart ; 4, 5, branches of \left septal division ; 6, free muscular ‘‘ moderator” bands
containing prolongations\ of bundle; 9, left auricle; 10, aorta; 13, pulmonary
artery.
from auricle to ventricle. It will be found that the node is made
up of closely interwoven fibres and a certain amount of fibrous
tissue. The main bundle is completely separated from the re-
maining musculature by fibrous tissue, and is made up of paler

THE HEART 43

staining fibres with larger nuclei.. The septal divisions are re-
eognised by similar differences. In the moderator band of a
human heart true Purkinje cells are not usually found, but the
terminal ramifications can be easily seen. The greatest help in
' tracing the bundle is a knowledge of its course as determined
by repeated dissections. This having been obtained, the “lie”
of a section will be more readily appreciated, and the probable
site of the A-V bundle located.

The Auricles of the Human Heart.—In the primitive heart

Fic. 4.—To show the antagonistic action of the musculatures of the right
auricle and ventricle (Keith). A, the position of the A-V groove at the end of
auricular systole ; B, its position at the end of ventricular systole.

depicted in Fig. 1 it is seen that the common auricle is a well-
marked outgrowth from the dorsal wall of the auricular canal.
Its ostium is indicated by a ring of thick circular musculature
_ (Fig. 1, 2.2). In the mammalian heart the development of the
basal wall of the auricular canal has led toa separation of the two
parts of the true auricle, namely, the appendices of the right and
left auricles. Their original continuity, however, is still preserved
_ by a ridge of musculature passing from the right auricle in front
_ of the termination of the superior vena cava to the left auricle.

44 THE HEART

The right auricle of the human heart, therefore, consists of
musculature from three sources—(1) Sinus venosus. (2) Auricular
canal. (3) Auricle proper.

The left auricle is composed of musculature from—(l) The
auricular canal. (2) The auricle proper. (3) Possibly sinus
venosus. All these parts are in the freest muscular continuity.

The Ventricles of the Human Heart.—The main mass of these
is true ventricle, although, as we have shown above, the invaginated

Fis. 5.—The heart from behind, showing the arrangement of the musculature
of the left auricle and ventricle (Keith). A’, the auricular base of the left ventricle
in systole of the auricle ; A, its position in ventricular systole.

portion of the auricular canal (4.4, Fig. 1) is represented by the
A-V bundle. The single ventricle of the primitive heart is a
diverticulum from the ventral wall of the primitive cardiac tube.
The double chamber of the mammalian heart is homologous with
it. The question of how the septum arose has, however, been
differently answered. The old idea was that the interventricular
septum grew up from the apex and thus divided the common
cavity. This view is undoubtedly incorrect. What really happens
is that the two ventricles are developed side by side from the

— EEO — ——

THE HEART 45

-yentral wall of the primitive tube. The fusion of their adjacent

walls forms the interventricular septum. The top part of this
septum, therefore, represents the part of the primitive tube which
has been least disturbed by the evolution of the ventricles. Now
it is particularly interesting to note that it is at this point only in
the mammalian heart that the invaginated portion of the auricular
canal has persisted in the form of the A-V bundle. This point
alone proves the mode of development of the interventricular
septum. Further, not only has the bundle been subjected to the
least possible amount of disturbance by this process of develop-
ment, but in the adult heart it is undoubtedly better protected
here than in any other possible situation (Keith and Flack). From
this one infers that the A-V bundle is likely to vary but little

in its course and must have a very valuable function to perform,

since it is so well guarded both during development and in its
final form.

The Bulbus Cordis.—In Fig. 1 it will be seen that a fifth
chamber exists in the primitive vertebrate heart, the bulbus cordis.
This chamber is generally supposed to be absent in the mammalian
heart, but the recent researches of Greil and of Keith render it
probable that this is not the case. The infundibulum of the right
ventricle is the homologue of this portion of the heart. Of the
original musculature of the bulbus probably but little if any is
left, it having become replaced entirely or, for the greater part by
that of the ventricle proper. There is therefore, as in the primitive
form, the freest muscular continuity in this part of the mam-
malian heart. This being so, we see that as in the primitive
cardiac tube we have in the mammalian heart free muscular
continuity from one end of the organ to the other—from the
representative of the sinus venosus to that of the bulbus cordis.

C. Tae Nervous ELEMENTS OF THE VERTEBRATE HEART

- The vertebrate heart is undoubtedly very rich in nervous
elements. As considerable stress is laid by some observers upon
this fact, it is important to ascertain as far as possible their dis--
tribution. These elements may be classified as (a) ganglion cells ;
(b) nerve fibres and nerve endings. The ganglion cells are usually

ed as the more important, since, as we shall see, the auto-
maticity of the heart is credited to them by some physiologists.

ae

46 THE HEART

Since, however, Apathy and Bethe make a similar claim for nerve
fibres, their distribution has now an added significance.

The nerve endings in the heart are both sensory and motor.
There is some doubt about the exact distribution of the sensory
fibres. It is held by some physiologists that they do not supply
the heart at all but only the aorta; others, however, believe that
they end as tree-like expansions very like those in fascia and
tendons, in both the epicardium and endocardium. According to
Smirnow, all the sensory fibres run in the depressor branch of
the vagus, since after section of this nerve in the cat no sensory
nerve endings can be detected.

The motor nerve endings come from both the vagus and the
sympathetic nerves. Gerlach states that the motor nerves accom;
pany the fibrous tissue among the heart muscle and finally end
as a delicate peri-muscular layer embracing the muscle fibres.
Heymann and Demoor claim that every heart fibre is surrounded —
by a nervous network right down to the apex of the heart.

In regard to the ganglion cells of the heart, Dogiel has divided
them into three types. The differences between the types are
mainly in the shape and size of the nucleus, the length of axon
and the number and form of the dendrites. The distribution of
the ganglion cells is a matter of prime importance. It is certain
that the auricular part of the heart is rich in these cells, which
are often arranged in groups corresponding to Remak’s, Ludwig’s,
and Bidder’s ganglia in the frog’s heart. These are respectively
situated at the sino-auricular junction, on the interauricular septum
and round the A-V groove. The distribution of ganglion cells in
the ventricle is a vexed point. Dogiel and his pupils find that
they undoubtedly occur in the upper third: of this chamber.
The lower two-thirds is, usually speaking, ganglion-free. This is
true for the hearts of such animals as the sheep, calf, dog, sucking
pig, duck, turkey, and chicken (Kasem-Beck). Ganglion cells have
also been found in the ventricle of the rabbit and ape (Vignal), and
of the mouse (Berkley), and in the ventricle and bulbus of the
frog (Dogiel).

Yet against this view such authorities as Engelmann, His,
Krehl and Romberg state that the ventricle contains no ganglion
cells either in warm-blooded or cold-blooded animals. In many
_ cases it appears to turn upon the interpretation placed. upon
certain histological appearances. For instance, Engelmann claims

THE HEART 47

to have proved that cells which Léwit termed nervous, were really
not nervous but endothelial. Another investigator, Schwartz, con- -
cludes that the so-called ganglion cells seen in the endocardium
and epicardium of the ventricle are really akin to if not actually
-mast-cells. Recently also Bethe claims to have demonstrated by
his methylene-blue method that ganglion cells exist at the apex
of the ventricle. He admits that they differ slightly from what is
regarded as the normal type of cell, but he believes that they are
true ganglion cells. As a critic says, many people would call this
ganglion cell a connective tissue cell.

The question of the distribution of both ganglion cells and
nerve fibres is therefore in a somewhat chaotic state. More work
is required—it is of the greatest importance to know whether
every muscle fibre has a nerve network surrounding it, and also
whether ganglion cells exist throughout the heart. Lastly, it may
be asked—Do nerve fibres exist in the A-V bundle? The question
must be answered in the affirmative. It is said to contain nerve
fibres and a few ganglion cells. Fredericq does not believe that
nerve fibres actually pass through the bundle, and brings as
proof evidence which we quote later on. He also states that he
has histological proof of this, but I have not been able to find
this piece of work.

D. Tue Heart as Aa MUSCLE

The chief properties of the heart should be studied on that
part of the heart which contains no nerves. From what has been
written in the previous section it will be obvious that this is a
matter of no little difficulty. In determining these properties,
however, most experiments have been made upon the apical part
of the ventricle, on the assumption that this contains no nervous
tissue. Although we shall have occasion to refer from time to
time to the property of automaticity possessed by the heart, we
shall not in this section discuss in which tissue, muscular or nervous,
_ that property resides, but shall leave it until later, when we shall _
_ consider this question together with the mode of conduction of ~
the excitatory wave which arises as the result of this property
of automaticity.
___ The properties of cardiac muscle may be studied either when
the heart is at rest or when it is beating. We shall consider the

48 THE HEART

former condition first, since it corresponds more closely to the
conditions under which the other forms of muscle are studied.

The heart may be reduced to this state of rest by four methods :—.—

(1) By placing it in physiological saline and waiting for it to
cease beating, the cardiac muscle being excitable for a variable
period after such stoppage. This method is more appropriate for
the hearts of warm-blooded than of cold-blooded animals, since
the latter may continue beating for days under these conditions.

(2) By shutting off the part of the heart possessing the greatest
automatic power. This is done in the Stannius ligature experi-
ment, more usually on the frog’s heart, in which a ligature is tied
round the sino-auricular junction. The same result can also be
obtained by cutting away the more automatic parts of the heart—
in other words, by making a ventricle preparation only.

(3) By stimulating the vagus most hearts can be reduced to

a standstill.

(4) By certain drugs, such as muscarine, a like condition is
obtained.

It must be stated, however, that under conditions 3 and 4
the normal properties of cardiac muscle are greatly altered, and
therefore the methods are unsuitable. Preference must therefore
be given to methods 1 and 2.

The ‘preparation being obtained, it is found that cardiac muscle,
like other forms of muscle, possesses the properties of excitability
and contractility. It responds to a single stimulus by a single
contraction. The stimulus may be either mechanical, thermal,
chemical, or electrical. The last is most commonly chosen, but it
is interesting to note with regard to the chemical stimuli that the
heart muscle responds to the stimuli for muscle but not to those
for nerve. Thus ammonia, dilute lime water, dilute mineral acids
when applied to the apex of a frog’s ventricle excite contraction or
a number of contractions. These, according to Kiihne, do not
excite motor nerves. The potent nerve stimulant, glycerine, on
the other hand, fails to excite a single contraction from such a
preparation.

Different parts of the heart possess different degrees of ex-
citability. This power of excitability, moreover, does not run
parallel with the degree of automatism possessed by the same
part of the heart. As an instance, the heart of the embryo chick
at three days possesses great automatic power, but only a small

- THE HEART 49

‘degree of excitability to artificial stimuli; later the automatism, |
specially that of the ventricle, decreases, while its excitability not-
ably increases. Similarly the auricle possesses at this time a greater
power of automatism than the ventricle, but the ventricle is the
“more excitable of the two chambers (Fano). The power of con-
- tractility also varies in different parts of the heart, being greatest
in the ventricle, the part of the cardiac tube developed for pro-
_ pulsive work.. But in dying this power is preserved longer in the
auricle than in the ventricle, the parts of the right auricle around
the superior vena cava and round the coronary sinus being the
last to lose this property.

; The muscle curve obtained as the result of the application of
a stimulus corresponds to that of an ordinary muscle. There is
the period of delay, the period of contraction, and the period of
relaxation. In point of time it approaches more nearly to that
of smooth muscle ; the latent period is well marked, and the period
of contraction is considerably slower than that of the sartorius
or of the gastrocnemius of the same animal. As with smooth
muscle, the heart appears to be more easily stimulated by gradual
than by momentary shocks.

As with skeletal muscle, the contraction’ of the heart can
be recorded under two conditions, namely, the isotonic and the
isometric. This has been done more especially by O. Frank. The
conditions in the heart, however, are not directly comparable
with those in the skeleial muscle. In the latter, under isotonic
conditions the actual shortening of the muscle under a constant
weight is measured ; in the heart, owing to the anatomical arrange-
ment of its fibres, it is impossible to do this. The isotonic curve
is therefore obtained by measuring the alteration in the size of
_ the cavity of the ventricle which occurs as the result of this shorten-
‘ing of the fibres. This is done by introducing a sound into the
_ ventricle and connecting it with a tambour. The isometric curve
| bed skeletal muscle is obtained by preventing the muscle from
shortening while the change in its tension is measured. The
allied condition is brought about in the heart by causing it to
contract against an insuperable obstacle, such as a tap introduced
> the circuit. The tension of the ventricle wall alters under
» conditions, but the length of the fibres remains the same.
is alteration i in tension is measured by a manometer inserted
n the ventricle and the insuperable obstacle.

D

Bits

a 4 =e *.

ae Te
-o
+
‘ ‘=
~ ’ ae

50 THE HEART

The skeletal muscle can also be studied under the combined
condition, namely, when “after-loaded.” Here the condition of
the muscle is isometric while altering in tension to overcome the
load, and isotonic after this load has been overcome and the muscle
begins to shorten. A similar state of affairs prevails in the heart.
The ventricle contracts under isometric conditions upon its load
of blood until the semilunar valves open, thenceforward under
isotonic conditions whilst its fibres shorten and its load is dis-
charged. The heart therefore corresponds normally to an after-
loaded muscle. Frank showed by his studies that the laws which
govern the contraction of skeletal muscle under these conditions
apply equally to the heart. Thus, as in skeletal muscle, the iso-
metric curve culminates before the isotonic. He found also that
the maximum of the isometric curve of the ventricle increases with
increasing tension up to a certain point, and then decreases. This

means that the contraction of the ventricle, as is well known, in- -

creases in force with the amount of its filling up to a certain point,
but after that it decreases and the ventricle dilates. Thus for
the frog’s heart Frank found the following figures :—

Volume incem. in ventricle 0 ‘18 ‘34 ‘47 ‘63 ‘84 ‘93
Tension mm. of mercury .12 60 68 66 60 59 58

During the isotonic curve the change of tension varies with
the load. Increasing load defers the beginning of the contraction,
shortens its duration, and diminishes the velocity of the move-
ment of the free end of the muscle. Similarly in the ventricle,
increased load—that is, increased resistance to the outflow of blood
from the ventricle—defers the beginning of the period of expulsion,
the .opening of the semilunar valves, shortens the period until
their closure, and diminishes the rate of flow of blood through
the aortic orifice, and consequently lessens the systolic discharge.
As an example from experiments upon the frog’s ventricle, if re-
sistance increases from 10 mm. to 40 mm. of mercury, the flow
decreases from -06 to ‘02 per second, and the period of expulsion
diminishes from 56 second to ‘51 second, and the systolic dis-
charge from ‘33 cc. to ‘08 cc. This method of studying the
ventricle under both isometric and isotonic conditions gives valu-
able information in working out the effects of drugs upon the
heart muscle.

So far we have spoken of the similarity between cardiac

a
—

THE HEART 51

and other forms of muscle as regards its response to a single
imulus. But there is this remarkable difference to be noted,
that whereas in other forms the response varies in force according
to the intensity of the stimulus, cardiac muscle responds with a
- maximal contraction to all efficient stimuli, be they minimal or
“maximal. This is sometimes termed “the all or nothing law” ;
therefore once a heart responds to a stimulus it is of no avail to
increase the intensity of that stimulus. It should be noted, how-
ever, that heart muscle may give in response to the first few stimu-
lations gradually increasing contractions, thereby manifesting the
so-called ‘“‘Treppe or staircase phenomenon.” This is explained
on the supposition that the first few contractions render the tissue
more excitable to that form of stimulation. |
Another peculiarity manifested by the heart muscle is in re-
sponse to rhythmic stimulation. If a ventricle preparation, giving
but one contraction to one stimulation, be treated in this way by
single induction shocks, it starts to pulsate in regular fashion,
but the frequency of beat is always less than the stimulation fre-
quency. The number of contractions obtained by this method
can be increased either by increasing the frequency of stimula-
tion or the intensity of current with the same rate of stimulation.
The same phenomenon can be produced upon the ventricle by
a constant current of appropriate intensity, the normal response
being twenty to thirty regular beats, after which it ceases. The
ventricle can also be made to give a similar rhythmic response
by injecting blood or normal saline into it at a suitable pressure.
Certain drugs, such as delphinin, are said to cause a series of
_ rhythmic contractions.
| A further peculiarity of cardiac muscle is that it cannot: be
tetanised. It is impossible to bring about a summation of stimuli
in the normal heart. This, however, is said to be possible on the
‘muscarine-poisoned heart, and on the heart stopped by excitation
of the vagus.
_ Thus far we have discussed the effect of stimulation upon
ag at rest. When we come to study the effect upon the
x heart, certain other remarkable differences from skeletal
a tle are revealed. For instance, if a stimulus be applied to
the rhythmically beating ventricle just before or during systole
is without any visible effect. The heart muscle is therefore
id to possess “‘a refractory period,” and the possession of this

*
-

52 THE HEART

property explains the inability to tetanise it. If, however, the
stimulus be applied during diastole, a contraction is produced
which is known as an “extra-systole.” Such extra-systoles are
followed by a longer pause than normal. This is called the “ com-
pensatory pause.” It is about equal in length to the pause fol-
lowing the normal beat plus the amount cut off from the previous
pause by the induction of the extra-systole. The ventricle there-
fore, owing to this property, makes but the same number of systoles
as usual in a given time. This is known as the “law of con-
servation of rhythm to physiological stimuli” (Engelmann).
The length of the compensatory pause is due to the refractory
period ; the impulse causing the normal contraction reaches the
ventricle while it is in a state of systole from the artificial stimulus,
and it therefore has no effect. The ventricle is then not stimu-
lated again until the next normal impulse arrives.

If, however, the ventricle be thrown into rhythmical contrac- ©

tions by a continuous stimulus, and an extra-systole produced by
a strong artificial stimulus, the ‘extra-systole so induced is not
-followed by a compensatory pause, for the continuous stimulus
still acting produces another contraction as soon as the refractory
period of the extra-systole is passed. This is adduced as proof
that the normal physiological stimulus is not continuous, but dis-
continuous, inasmuch as there could be no compensatory pause
if it were not so.

Another important point to be noted is that the compensatory
pause does not -follow an extra-systole induced at the ven cave.
It therefore follows that all extra-systoles observed to be followed
by a compensatory pause are produced by a stimulus applied to
some other part of the heart (e.g. auricle or ventricle). It also
follows that the stimulus is not conducted from outside to the
venee cave, but actually arises there.

Like other forms of muscle, the heart muscle is said to possess
the property of tonicity This is masked in part by the incom-
plete relaxation of the heart between the beats, since as Gaskell
points out the degree of relaxation depends not only upon the
tonicity of the muscle, but also upon the rate of beat, which is
usually such that the heart muscle probably never completely re-

laxes. An alteration in tone can therefore only be manifested —

when the rate of-beat remains the same. The little but distinct
evidence that exists for this change is derived from the action of

Ka

x
Fr
-

THE HEART 53

_ eertain solutions and drugs upon the beating ventricle. If a frog’s
ventricle be placed in a weak solution of caustic soda (1 in 20,000
of normal saline) it relaxes less and less between the beats and
eventually stands still in systole, whereas if lactic acid (1-10,000
- normal saline) be used the contractions become less and less, so
that finally the ventricle stops in a state of complete relaxation.
Similar results to that with alkali can be obtained by such drugs
as digitalis and veratrine, and to that of acid with muscarine.
Moreover, acid solutions antagonise the effect of alkaline on the
same preparation, as does muscarine that of digitalis. The heart
muscle, therefore, would appear to be possessed of a certain degree
of tonicity which, like the other properties of cardiac muscle,
probably varies in the different parts of the heart.
_ Another peculiar form of tonicity has been observed by Fano
(quoted by Gaskell) upon the heart of Emys Europea. If this
heart be clamped in the A-V groove, the auricles exhibit a
rhythmical variation of tone. A similar phenomenon has been
seen by Botazzi in the frog’s heart. It apparently does not occur
in many cold-blooded animals. At present a satisfactory explana-
tion is wanting. bi

Lastly, the heart possesses the properties of automaticity,
rhythmicity, and stimulus conduction. Do these properties reside
in the heart muscle itself or in the nervous tissue abounding in
the heart? This is the vexed een which we discuss in the
owing section.

EZ. Tue Sire or ORIGIN AND THE MopE or CONDUCTION OF
THE EXxcITAToRY WAVE

By the site of origin is meant the kind of tissue, muscular or
nervous, in which the heart impulse arises. A long controversy
has raged around this point, and much fruitful research has been
_ the outcome. It is necessary to keep clearly in mind the difference
_ between the site of origin of the excitatory wave and the mode

in regard to the site of origin of the excitatory wave are quoted
“as evidence as to its mode of conduction. Certainly it must be
granted that if the excitatory wave be found to arise in one form
ssue ae is highly probable that it will also be conducted by
tissue ; but it is not necessarily the case. There are several

_ of its conduction. These are frequently confused, and experiments ——

Pt

54 THE HEART

possibilities. The excitatory wave, for instance, may conceivably

arise in nerve and be conducted by nerve. This is the neurogenic
theory. Or the excitatory wave may arise in the heart muscle
and be conducted by muscle. This is the myogenic theory. These
certainly seem more probable than either (1) that the excitatory
wave may arise in nerve and be conducted by muscle; or (2)
that it may arise in muscle and be conducted by nerve. Even
here the possibilities do not cease, for the co-ordination of the
movements of the different chambers of the heart is essentially
a complicated yet all-important process, so that it may well
be that, arise the excitatory wave how it may, both muscle and
nerve may be called into play as conducting agents in order that
the proper sequence of contraction of the different chambers of the
heart may be assured.

Taking the first possibility, that the excitatory wave may arise _

in nervous tissue and be conducted by that tissue, let us consider
the evidence for and against it. This view gained sway in the
middle of the last century chiefly perhaps because it offered a
satisfactory explanation of the great discovery by the brothers
Weber of the action of the vagus nerve upon the heart. At that
time such an inhibitory influence could only be explained on the
analogy of nervous influence of centres situated in the central
nervous system, such as the respiratory centre of the medulla and
the motor centres of the spinal cord. The ganglion cells, there-
fore, were thought to be the central apparatus of the heart,
sending out a continuous stimulus to the heart muscle. Different
afferent impulses to this central apparatus modified the stimulus
in different ways. The very plausibility of the view immediately
accorded it a place as a theory without any very substantial
evidence. Its chief support is the experiment of Stannius, now
known as the Stannius ligature experiment. If in the frog’s heart a
ligature be placed around the sino-auricular groove and tied tightly,
the auricle and ventricle of the heart are reduced to a standstill ;
in consequence, it is asserted, of the cutting off of the influence
of Remak’s ganglia in this neighbourhood. The sinus, however,
continues to beat. If now a ligature be placed round the
A-V groove and tied, the ventricle again starts to beat, owing,
it is said, to the stimulation of Bidder’s ganglia in this region.
Bidder’s ganglia are therefore looked upon as a subsidiary
centre normally under the control of Remak’s at the sinus. In

‘

THE HEART 55

further support of this view Kaiser claims to have shown that,
after extirpation of Bidder’s ganglia, this second ligature no longer
has any effect in starting the ventricle. Now a stimulus applied
is followed by only one contraction instead of by a series of con-
tractions. We shall refer to this experiment again later on.
Kronecker and Schmey claim that when a needle is thrust into
a certain spot in the dog’s ventricle, the heart immediately falls
into fibrillary contractions as far as the ventricles are concerned.
The needle is thrust into the ventricular septum at the lower end
of the upper third. The experiment frequently fails. It is
adduced, however, by its authors as evidence of the neurogenic
theory.
The experiments of Carlson upon the heart of a horse-shoe crab
(Limulus) undoubtedly afford evidence of neurogenic origin of a
heart beat. The heart in this case consists of a tube 10 to 15 cm.
long, divided into segments by the origin of arteries. During
systole all the parts appear to contract simultaneously, although
it is probable that there is really a rapid wave of contraction.
Three nervous strands (one median and two lateral) run along
the heart and anastomose freely. The median contains ganglion
cells, and one especially large ganglion. This strand can be easily
separated from the heart without injuring the latter. Fine
branches pass into the muscle substance. Carlson has shown that
if the whole of this median nerve be removed, the heart imme-
diately ceases to pulsate ; if a part only be removed, then activity
ceases in the corresponding portion of the heart. The ganglionated
chain therefore appears to be the site of origin of the excitatory
wave in this heart.
As regards the conduction of the impulse the neurogenic theory
holds that it is conducted by nerves. The delay in the passage
from auricle to ventricle is said to arise in Bidder’s ganglia.
The chief points in the evidence brought forward for nervous
conduction are—
(1) The assertion by Kronecker that he has produced allo-
_ thythmia- (inco-ordination of auricle and ventricle) by cutting a
nerve running between auricle and ventricle.
_ (2) At first the fact that in the mammalian heart no muscular
_ connection was known to exist between auricle and ventricle. For
instance, MacWilliam, as the result of his researches, came to the
aclusion that in the mammalian heart, at any rate, the mode

56 THE HEART

of conduction from auricle to ventricle must be nervous, as he
could find no muscular path. Since the discovery of the A-V bundle
this piece of negative evidence is of less value; but the fact that
the bundle contains nerve fibres is insisted upon by the upholders
of the neurogenic theory. This point we shall deal with when
considering the evidence of muscular conduction by the A-V
bundle.

(3) In the heart of Limulus Carlson has shown that section of
the nervous strand immediately abolishes the synchronism of the
different parts. The parts on either side of the cut continue to
pulsate, but with a different rhythm. This points to nervous
conduction of the master rhythm. Further, it is interesting to
note that in this heart, so long as the nerves are intact, section of
the muscle produces no inco-ordination whatever.

In estimating the value of these experiments of Carlson it
must be pointed out that the muscle tissue of this invertebrate
heart differs very materially in its properties from that of the
mammalian heart, being in fact much more akin to mammalian
smooth muscle. It possesses no refractory period, gives sub-
maximal contractions, and is capable of tetanisation.

It was in 1882 that the first serious criticism of the neurogenic
theory was advanced. Gaskell came to the conclusion, as the
result of his experiments upon the heart of the turtle, that in cold-
blooded animals the heart’s excitatory wave arises in the heart
muscle itself and is conducted by it. He showed that if the
ventricle be warmed its beat was not quickened, whereas warm-
ing of the sinus caused a quickening of the whole rhythm of the
heart. This therefore proved that the stimulus is discontinuous
and not continuous, as was thought before. But were the nerve
cells concerned in the origin of the excitatory wave? Gaskell
found that if the Stannius ligature be applied to the turtle’s heart,
the effect at first is essentially the same as with the frog’s heart.
Soon, however, the auricle starts beating with its own rhythm,
slower than that of the sinus, and the ventricle follows it. If
now the second ligature be applied, the ventricle stops for a
moment, but quickly resumes beating with its own rhythm, which
is slower than that of the auricle. Therefore in the same heart it

»

:
i

is possible to obtain the sinus, auricle, and ventricle beating with a

different rhythms. It seemed that in such a case as this it would
be strange for nerves to set a different rhythm in different parts

*
’ «

THE HEART 57

of the same heart; and, knowing the muscle of the heart to vary
in these different portions, it was more probable that the difference
in power of originating the automatic rhythm lay in the heart
muscle itself. This was proved to be the case. Gaskell found that
small strips of muscle from the different parts of the heart, so small
as to contain no ganglion cells, show the same power of developing
different rhythms ; a piece of ventricle, for instance, from a well-
nourished animal beating for thirty hours. Gaskell, as we have
said, explains the different degrees of automatism by the variation
in the type of muscle. The more “ embryonic ”’—that is, approach-
ing the type seen in the embryo—possesses the greatest automatic
power. This being the case, then stimulation of the musculature
of the sinus or of the auricular ring should originate a series of
contractions. Gaskell showed this to be so, proving conclusively
at the same time that the experiment of Kaiser in regard to the
function of Bidder’s ganglia was incorrect.

Gaskell’s result may be summarised as follows :-—

Stimulation of auricle or ventricle . =. One contraction.
Stimulation of Bidder’s ganglia ; - No contraction.
Stimulation of the auricular ring. . Series of contractions,

Consequently the ring musculature and not the ganglia were con-
cerned in originating the rhythm. Further support in this direc-
‘tion came from Munk, who also showed that a series of contractions
was the normal response to the excitation of this musculature.
Ewald found and confirmed by microscopic examination that in
only two cases out of twenty-nine were the ganglion cells or nerves
injured as the result of the excitation of the ring musculature,
which, however, in all cases responded with a series of contractions.
In the twenty-five years following Gaskell’s first work much
has been done in endeavouring to support the myogenic con-
tention. Engelmann and his pupils have been particularly
strenuous in upholding it. During this time, however, the neuro-
_ genic school have provided but little new evidence for their some-
what slenderly-founded theory, their chief work consisting in
_ endeavours to refute the evidence brought forward by ‘the
_ myogenic school. The chief points which have been offered as
_ evidence are :—

(1) Engelmann isolated portions of the great veins said to
contain no ganglion cells and showed that they beat automati-

——

| a
‘ > .
‘ .
‘ » a’

58 THE HEART

cally; a small piece (2 cmm.) of the sinus of a frog beat for
four days and recorded 17,000 contractions.

(2) In certain molluscs, arthropods, and tunicates, the heart
undoubtedly contains no ganglion cells but possesses automatic
rhythm.

(3) The apex of the mammalian heart, said to have no nerves
whatever, shows slow rhythmic contractions.

(4) The embryonic heart beats when no ganglion cells have
invaded the heart, and before the muscle and nerve have become

differentiated (His). In the chick, the heart of which pulsates -

36 hours after the beginning of hatching, no ganglion cells appear
until the sixth day ; in the human heart Pfliiger saw pulsations at
the beginning of the third week, whereas no ganglion cells are said
to occur until the end of the fourth or the beginning of the fifth
week. Fano found that if he divided the heart of a chick into
three or more parts, all the parts pulsated—the frequency being
greater the nearer the part was to the venous end—although, as
we have seen, the ventricle at that period was the more excitable.
W. His has also found differences in the behaviour of different
parts of the heart towards drugs such as muscarine and digitalis,
the ventricle being the most affected. The inwandering of the
ganglion cells leads to no noticeable effect on this. This being
the case, it is difficult to believe that later on they should take
over the function of initiating the heart rhythm.

(5) Hearts can be revived many days after death—even the
hearts of children dead of disease. In ten such hearts only three
gave negative results. The heart of a boy dead of pneumonia
revived in all parts 20 hours after death. In the case of the heart
of an ape, Hering recovered the heart after 44 hours, and then froze
it. After 28 hours 32 minutes the heart was again resuscitated.
If now the ganglion cells be the site of origin, then Ringer’s fluid
must possess the power of enabling them to recover their functions ;
but if Ringer’s fluid have not this power, then the ganglion cells
cannot have the power of automatism. Now Langendorff and
others have shown that sympathetic ganglia and fibres die very
quickly. Hering found in the rabbit that the pre-ganglionic
cervical sympathetic was without action 15 minutes after death,
the post-ganglionic 33 minutes after death, the vagus on the heart

55 minutes after death. The corresponding times for the cat were
11, 26, and 40 minutes. It was not found to be possible to restore

\

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.

THE HEART 59

_ the functions of the cervical sympathetic by perfusing with Ringer’s
solution, whereas the irritability of the vagus could be restored for
some time, and that of the acceletor almost indefinitely.

It is in the tissue of the sinus in the frog’s heart that the
automatic power resides. This is the part of the heart which can
be affected by such agents as heat and cold. Destruction of the
sinus or cutting it off alters the rhythm of the remaining portions
of the heart. One would expect, if the results obtained upon the
frog’s heart be applicable to the mammalian heart, that similar
results should be obtained by experimenting upon the parts repre-
senting the sinus. Such indeed is the case. At the junction of
the superior vena cava with the auricle Adam has succeeded in
altering the mammalian heart rhythm by the application of heat
and cold. Hering has shown that the rhythm in the dog can be
completely changed by a cut in this region. Langendorff has
obtained somewhat similar results with the Stannius ligature
experiment upon the mammal. The results were not so marked
as with the frog, the period of rest being slight, and the heart
resuming its beat more quickly, although with a different rhythm.

a As we have seen, the sino-auricular node is situated in this region,
and it may well be that this is the spot acted upon in these experi-
ments. Experimental evidence to this effect, however, is still
wanting, and the true function of this node has yet to be worked
out. In the meantime it has been suggested that in view of
its embryonic structure it is kkely to possess great automatic
properties, and that seeing how carefully it is supplied with blood,
and how intimately the nerves of the heart come into contact
with it, this isolated node of tissue is probably the site of origin
of the heart’s impulse. On the other hand, also without physio-
logical evidence, Tawara has claimed that the heart’s impulse

_ normally arises in the A-V node, which he has termed the “ cardio-
motor centre.” No proof of this is as yet forthcoming, but the
view more generally held, although as yet without definite evi-

dence, is that the A-V node must’be regarded as a subsidiary centre,
and that it is only under certain circumstances that the heart

-thythm is initiated there. While dealing with such hypothetical

_ problems it may be suggested that the possible explanation of the

effect of the first Stannius ligature is due to the cutting off of the

| tic tissue at the sinus, ¢.e. in the case of mammalian heart
oly the sino-auricular node. Under these circumstances the

~~ —_——o = :
. - bee
J ” =

*
ty

60 THE HEART

auriculo-ventricular node after a time takes up the function of
initiating the heart rhythm. Examples of this “nodal rhythm ”
have been recorded clinically by Mackenzie.

Coming now to the evidence of muscular conduction, it will
be remembered that there is no histological reason against it,
since the heart muscle is now regarded as a continuous network.
The earliest experiment on cold-blooded. animals was the well-
known zig-zag experiment of Engelmann, in which the ventricle
of the frog is so cut that it is claimed that all conducting nerves
must be cut and yet the impulse still passes. Gaskell also showed
in the tortoise that section of the well-marked coronary nerve had
no effect on the passage of the impulse, whereas the clamping
of the muscular tissue induced varying degrees of allorhythmia
(2A :IV, 3A: IV, 4A: IV), according to the tightness of the clamp.
Gaskell also showed that section of the part of A-V grooves .
containing the most nerves had no effect upon the ventricular
rhythm.

MacWilliam came to the conclusion that in the eel the con-
duction of the impulse was by muscle. He also drew attention to
the sino-ventricular rhythm, whereby the ventricle can follow the
rhythm of the sinus without the auricle being influenced. In this
case the impulse arising in the sinus passes down the basal wall
(Fig. 1) and thence to the ventricle. MacWilliam thought there
was evidence of such a rhythm in the mammalian heart. We
may here point out that it is indeed quite possible, for the exci-
tatory waves arising in the great veins may conceivably, under
certain conditions, pass down the interauricular septum which
corresponds to the basal wall, and thence to the ventricle, without
affecting the other parts of the auricle during its passage.

As regards the evidence of muscular conduction in the
mammalian heart, Fredericq has brought good evidence to show
that such is the case in the auricles. He found that the two
auricles remained co-ordinate so long as he left a thin strip of
muscle connecting them. It did not matter where this strip was,
whether in neighbourhood of superior vena cava or of inferior
vena cava or coronary sinus. When, however, he cut this strip,
then he found that the two auricles became inco-ordinate. It is
interesting to note, however, that the ventricle continued to beat =
with the same rhythm as the right auricle. He argued that con- :
duction in this case was muscular and not nervous, since the bridge

u
F f
*
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THE HEART 61

of tissue might be situated in any position. Histological investiga-
tion proves this free muscular continuity (Keith and Flack). With
regard to evidence of muscular conduction between auricle and
ventricle in the mammalian heart, it is usually held that the
A-V bundle effects this, and that the conduction by it is muscular.
The evidence that the A-V bundle is the sole passage of conduction
is also tolerably strong, although some investigators bring results
which appear to the contrary. The chief evidence in favour is
as follows :—

(1) Hering cut in the region of the A-V bundle in four dogs,
and in three cases out of four obtained allorhythmia. Tawara
showed by histological investigation that in three only was the
bundle cut ; the fourth had escaped.

(2) Erlanger compressed the bundle in dogs by means of a
specially-devised atriotome, and succeeded in obtaining varying
degrees of arrhythmia and finally allorhythmia. Retzer confirmed
histologically the damage done to the bundle. |

(3) Humblet has successfully obtained allorhythmia in dogs on
many occasions by ligaturing the A-V bundle. No allorhythmia
was produced when any other part of the septum was tied.

(4) The evidence afforded by syphilitic disease of the bundle
in certain cases of Stokes-Adams disease. Several very satis-
factory cases with tracings and post-mortem examination of the
heart have been published.

On the other hand, Kronecker states that in rabbits he is unable
to obtain any allorhythmia by ligature of the A-V bundle, and in
this he is confirmed by his pupil Imchanitsky. In some cases the
bundle was certainly not tied, but in others it is claimed to have
_ definitely been so. It may be that the heart of the rabbit affords
an exception, since Biggs also appears to have obtained uncertain
results upon the rabbit’s heart. An interesting point, however, is
that Kronecker always attempted to tie the bundle through the
left auricle, and Humblet found in dogs that he was not successful
by this method. All the observers mentioned above attack the
bundle through the right auricle. It is undoubtedly the more
certain method. There is great danger of getting above “the

_ bundle or only obtaining part of it from the left side, owing to
_ the manner in which the left septal division comes off.
The main evidence is undoubtedly in favour of the A-V bundle
_ being the sole path for the transmission of the impulse from auricle

a
’

62 THE HEART

to ventricle in the mammalian heart. But it does not necessarily
prove muscular conduction, since the bundle contains nerve fibres
and a few ganglion cells. Fredericq, however, states that he has
destroyed all the nerves in the bundle and its neighbourhood by
ammonia, but yet got no evidence of allorhythmia. He states
also that histological evidence shows that the nervous elements
of the bundle do not extend right through it. According to
Fredericq the mode of conduction in the bundle is undoubtedly
muscular. The opinion of Fredericq is weighty and all the more
interesting since formerly he held the neurogenic view. Even now
he holds that under certain conditions there is a nervous con-
duction in the heart. He bases his view upon the following experi-
ments. As long ago as 1886 he found that with feeble indirect
shocks he got these results :—

Both ventricles stopped.

Applied to one ventricl ‘ ; : : ;
PP pore Both auricles continued beating.

Both auricles stopped.

Applied to one auricle * ( Both ventricles continued beating.

He came to the conclusion, therefore, that there must be some
abnormality in the conduction in these cases, since ordinarily he
could obtain reciprocal conduction, whereas this mode of con-
duction affected both auricles and both ventricles, but did not
connect auricles to ventricles. More recently he found that if he
threw the heart into fibrillary contractions he obtained the same
results. The fibrillary contractions arising in one auricle pass
quickly to the other, but not to the ventricles ; similarly with the
ventricles, from ventricle to ventricle but not to the auricles.
Fredericq thinks that fibrillary contractions pass quickly by
nervous means, and adduces the above experiments as evidence
that the A-V bundle contains no nerve fibres passing throughout
its course, since fibrillary contractions never pass from auricle to
ventricle. On the other hand, the rhythm of the ventricle is
normally that of the auricle, and is influenced whenever that of
the auricle is altered. Therefore the heart impulse passes by
muscular tissue and traverses the A-V bundle in its passage from
auricle to ventricle. The rate of conduction of the impulse along
the bundle is explained by the character of the muscle tissue of
which it is composed, sincé Fano has shown that the rate of con-
duction in cardiac muscle varies according to the stage of develop-
ment. It would therefore seem that the difference in structure

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THE HEART | 63

- of the bundle in different hearts has, in a measure at least, to
do with the rate of conduction required for that particular heart.
In the dog’s heart Stassen finds the time taken is ‘08 to "10 of a
second.

To summarise, the chief points usually adduced in favour
of muscular conduction in the vertebrate and especially in the
mammalian heart are :—

(1) The zig-zag experiment of Engelmann and the bridge
experiment of Fredericq.

(2) There is muscular connection between auricle and ventricle.
Disturbance of conduction follows cutting or compression of this
| connection.

, (3) There is no effect upon stimulating or cutting the nerves
from auricle to ventricle.
(4) The conduction of the excitatory wave may occur after the
| nerves have degenerated.
: (5) The rate of conduction is more in accordancé with muscular
conduction.
| (6) Conduction takes place from the point of stimulation in all

directions.

(7) Reverse conduction occurs from ventricle to auricle.

The balance of evidence lies in favour of the myogenic theory.
Certain objections, however, may be urged against it. For
example, the evidence brought from the invertebrate kingdom in
its favour is no more applicable than that obtained upon the heart
of Limulus. Against the zig-zag experiment may be brought the
histological evidence of certain observers. If every fibre is sur-
rounded by a nervous network, then that network may manifestly
be the conducting medium. As to the rate of conduction, it has
been shown by Nikolai and Garten that non-medullated nerves
conduct at a rate compatible with that of the excitatory wave of
the heart. On the other hand, Békelmann has found that the non-

_ medullated terminals in the cornea of a dog are not appreciably
slower in conduction than ordinary nerve. More recently Bethe
has made.experiments on the warm-blooded heart, and concludes
that the rate of conduction of nerve in the dog is 130 to 225 cm.
per second—a result quite in accordance with that required for this
heart. Bethe also states that it is difficult to induce degeneration
of nerve in the manner usually employed, namely, by placing a
ligature round the heart. He himself has been surprised to find

64 THE HEART

how difficult it is to induce degeneration in an isolated nerve
by a tight ligature. Anatomical evidence of such degeneration
in the heart must be brought, and at present this has not been
furnished.

In regard to the proofs offered for the automaticity of the
heart residing in its muscle, considerable importance rests upon the
evidence obtained from the embryonic heart. Here one may object
that this embryonic tissue is probably neither muscular nor nervous.
Bethe claims that recent methods show that from it both muscle
and nerve cells develop. The action of muscarine upon the heart
before the inwandering of the ganglion cells is also brought as
evidence on this point. If this be the case, it leads on to the idea
that the automaticity of the adult heart may possibly reside in
a similar tissue neither muscular nor nervous. This tissue, akin
to nerve-muscular cells from which the heart is developed, may

be shut off at any early stage of development for this special ©

purpose of leading the automatic rhythm of the heart. May it
not also in some ways correspond to the form of tissue in the
myoneural junctions, in being easily affected by nervous influences
and manifesting the effect upon the adjacent muscle. Why, more-
over, may it not be acted upon by certain internal secretions, thus
providing the heart with a further reflex mechanism for preserving
the well- -being of the body as a whole ?

Again in regard to the conduction of the impulse, it is possible
that the conducting mechanism of the heart is developed from
such a tissue, becoming nervous in one form of heart, muscular in
another, according to the requirements of the organ in that special
genus. This would explain the discrepancies in the evidence from
the invertebrate kingdom. Then again the Purkinje fibres of the
sheep’s heart are not seen in the human. This is probably some-
thing to do with the requirements of co-ordination. The Purkinje
fibres are totally different from the surrounding musculature—it
is difficult to call them muscle; but it is easy to understand how
such a fibre can be differentiated from a tissue capable of giving
rise to both muscle and nerve. From such a tissue, moreover, a
conducting mechanism can be evolved presenting different histo-
logical appearances, but having the requisite rate of conduction
for the co-ordination of that heart.

The above are the chief facts in regard to both the neurogenic
and myogenic theories. Neither theory is a dogma—one may

\ ;
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THE HEART 65

survive, both may pass away; but that only further anatomical
and physiological research can show.

F. THE MovEMENTS OF THE HEART IN SITU

By virtue of the properties enumerated above the heart co-
ordinates itself to meet the circulatory needs of the body. More
research is needed before one can speak with certainty upon the
exact movements made by the heart in the unopened thorax,
although a considerable amount of work has been done on the
subject (Ludwig, Haycraft, Keith). As emphasised by Keith, the
heart has certain fixed fulcra from which it executes its normal
movements, and the moment the thorax is opened these are taken
away, and the true movements made by the heart are in part
obscured. These fulcra are as follows :—

(1) The venous mesocardium, or the part of the pericardium
attached around the great veins (Fig. 4, over a, 7, 7, and b).

(2) The arterial mesocardium, or the part of the pericardium
attached around the great arteries (Fig. 4, over g and f).

Except at these two points the heart lies absolutely free
within the pericardium. But these mesocardia are attached to
the surrounding structures, and it is by this means that steadiness
is obtained. For instance, the part attached to the venous end
is bound to three structures :—

(1) To the root of the lungs;-and by the lungs to the wall of
the thorax.

(2) To the diaphragm, especially to the crura.

(3) To the structures in the root of the neck through the fibrous
tissue surrounding the superior vena cava.

Now to this fulcrum the longitudinal muscle of the auricle is
attached, and it is obvious that when the thorax is opened the
auricle can no longer perform its normal movement.

___ As we have seen, the heart’s excitatory wave arises in the great
veins, especially in the neighbourhood of the sino-auricular groove
between the superior vena cava and auricle. Of this there is
physiological proof, since, as stated above, it is only in this region
that the rhythm of the heart can be modified. The wave passes
om here to all parts of the heart, and they respond to it in
orderly sequence. We should expect, perhaps, that since it arises
loser proximity to the right auricle, this auricle would contract

E

66 THE HEART

slightly before the left, since the wave presumably has less ground
to cover to fire off the right auricle. It is usually stated, how-
ever, that the auricles beat simultaneously (cf. Tigerstedt and other
authorities). According to Arloing and Doyon, however, Chauveau
appears to have stated that in the horse the right auricle beats
before the left. Fredericq also noticed this in his records on more
than one occasion, especially when the heart was beating feebly and
slowly. Recently further proof has been forthcoming under his
direction. Schmidt-Neelsen finds that normally the right auricle
precedes the left. If, however, an extra systole be induced by
stimulation of the left auricle, then that auricle precedes the right.
Another interesting observation made by him is that when the
auricles are induced to beat by stimulation of the ventricle, the
right more often precedes the left, but the results are variable.
When the heart beats during excitation of the vagus, the normal

order of beat is preserved. Stassen finds that in the dog the right

auricle precedes the left by ‘02 to ‘03 second. He also finds that
the ventricles do not beat simultaneously, but that the left nor-
mally beats in the dog ‘03 to ‘04 second before the right. But
when it is stimulated electrically the right precedes the left by
a greater time than the left normally precedes the right. From

this Stassen infers that there is a form of “‘ antidromic ”’ conduction -

in the A-V bundle, since if the left be similarly excited, the
interval before the right is the same as normal.

When the auricle beats in the lower vertebrate heart, regurgi-
tation is prevented by the action of the venous valves. In the
mammal these valves have disappeared, and the prevention of re-
gurgitation into the great veins is not altogether effectual. It is on
this account that the jugular pulse can be recorded over the jugular
bulb even in health. There is undoubtedly a guillotine action by
the tenia terminalis tending to prevent regurgitation, but this is

insufficient especially with high pressures; and according to the ©

degree of its insufficiency, so will the jugular tracing vary. Re-
gurgitation through the inferior vena cava cannot be prevented
by muscle, since there is none. The most important factor here
is undoubtedly the high abdominal pressure, and indirectly there-
fore the tone of the belly wall. The whole system of abdominal

and thoracic veins may be looked upon as a large venous cistern, —

having a capacity in man of about 430 c.c. The abdominal

portion has by far the greater capacity (Keith). The blood is

ia =

THE HEART 67

kept in this cistern by valves, e.g. femoral and jugular, and the
. caused by the body movements must therefore send the
blood on to the right heart.

The chief function of the right auricle, however, is to expel the
blood into the right ventricle at the end of joint diastole, and
thereby place its walls on a certain tension. According to this
degree of tension the heart muscle will contract. Within certain
limits, the greater the tension, the more powerful the contraction.
It is by this means in part, that the amount of blood passing to
and from the heart is regulated to meet the needs of the body in
general.

It is necessary, therefore, to inquire into the movements acc :>m-
panying auricular systole. The key to them lies in the study of
the auricular and ventricular musculature. .The function of the
musculi pectinati of the auricle has been neglected. In the human
heart they are fifteen to eighteen in number, and from 1 to 2 mm. in
diameter. They take origin from the right tenia terminalis, and
} end in the musculature of the auricular canal in the A-V groove.
i The tenia terminalis is a fixed point through the venous meso-
-_ cardium; therefore when the musculi pectinati contract, they are
2 _ drawn towards the fulcrum, the ventricle being also drawn up at
the same time. It will therefore be seen that this movement
which empties the auricle at the same time draws the ventricle
over its load. There is therefore in auricular systole a movement
of the A-V groove towards the. venous base of the heart. This

function of the musculi pectinati has been well demonstrated by
é injecting warm wax into the auricle, the casts so obtained showing
that the musculi pectinati shorten to quite half their diastolic
___ length during systole (Keith). In hearts from cases of back pres-
sure there is great prolongation and hypertrophy of these muscles.
Now an anatomical axiom is that every muscle in the body has
its opponent, the opponent in this case being part of the inner
longitudinal layer of muscle of the right ventricle. Inspection of
_ the ventricle will show two layers of muscle—an inner longitudinal
and an outer spiral layer. The longitudinal layer can be divided
into two systems—(1) That to the auricle or venous base; (2) that
to the aortic exit or arterial base. The significance of the system
to the arterial base is perhaps at first not quite apparent. Accord-
ng to Keith, its function is to act with the spiral fibres in
endering the apex a fixed point. The spiral fibres will tend by

~~

t a

68 THE HEART

their contraction to lengthen out the ventricle ; the longitudinal
layer from the arterial base will tend by their contraction to
shorten it. Between them, therefore, they render the apex a
fixed point. The apex thus being fixed, the force of their com-
bined contraction is to empty the ventricle of its contents. The
significance of the longitudinal layer of trabecule to the auricle is
quite clear. This layer is the opponent of the musculi pectinati
of the auricle. The apex being a fixed point, its contraction in
ventricular systole draws down the A-V groove towards the apex.
By the action, therefore, of these opponent sets of muscles in the
auricle and in the ventricle, the well-known to-and-fro movement
of the heart at the A-V groove is executed (A, B, Fig. 4). It
should be noted that this movement of the A-V groove towards
the apex in ventricular systole expands the auricle and at the
same time produces therein not only more room but also a
negative pressure facilitating the flow of blood thereto.

During joint diastole two things happen—(1) The base of heart
replaces itself owing to the relaxation of the ventricular fibres ;
(2) the ventricle opens out to fill with blood. A glance at the
tracing of the jugular pulse given on page &8 will reveal these
movements of the auricle and ventricle during the cardiac cycle.
The positive wave a takes place during auricular systole ; the fall
v is due to the contraction of the ventricle inducing the negative
pressure in the auricle ; lastly, during diastole there is, first, a rise
due to the reposition of the A-V groove, and secondly, a fall owing
to the relaxation of the ventricle.

Thus far the right side of the heart has occupied our attention.
The manner in which the left auricle acts is more obscure, and has
had far less attention paid to it. It is situated between the roots
of the lungs, being firmly attached to each. By this means it is
bound down in the unop2ned thorax to the chest wall. Behind
it are the unyielding structures of the posterior mediastinum.
Above, too, ‘are unyielding structures, the pulmonary arteries and
bronchi; to the latter and to the trachea the upper border of the
left auricle is firmly bound.. 'There is left, therefore, only (a) the
anterior surface in contact with the ascending aorta, and (6) the
floor in contact with the left \ventricle. Anatomical evidence,
therefore, points to the fact that in systole of the left auricle the —
anterior wall moves backwards and the ventricle upwards. The
former movement would involve a \backward movement of the

gs

THE HEART 69°

- aorta also, and it seems probable that in auricular systole the be-
ginning of the aorta swings back and to the right, while in systole
of the ventricles it moves forwards and to the left. Absolute
physiological evidence of this movement is wanting, but Keith
has pointed out :—
‘ (1) That with the heart in situ, if the auricle be filled with
injection of wax, the aorta is pushed forwards and recedes when
it is emptied.
_ (2) In mitral stenosis and cases where the left auricle is dilated
_ + the aorta is pushed forward.

(3) No other movements are available on anatomical con-
siderations.

(4) There is a portion of the pericardium so arranged as to act
as a bursa for this movement.

(5) The attachment of the musculature at the ‘Gnternurieulat
septum is such that its only action can be to serve in this movement.

Considering the musculature of the left auricle in more detail,
we find that, unlike the right auricle, there are no pectinate
muscles. This is due to its being developed as mentioned above,
mainly from the auricular canal. The place of the pectinate
musculature is taken by a series of muscular bands (Fig. 5) which
are inserted into the inferior vena cava, and through it into the
pericaridum and diaphragm. Chief of these bands is the left
tenia terminalis (h, Fig. 5) which, arising in front at the superior
vena cava, sweeps round to the. left in the anterior wall of the
left auricle, and turns down between the auricular appendix and
left pulmonary veins, to end in the inferior vena cava. Above
and laterally the left auricle is attached to the roots of the lungs
by the pulmonary veins and the fibrous venous mesocardium
(xx, Fig. 5). The musculature of the left ventricle is essentially
the same as the right. The outer spiral fibres (Fig. 5) and the
inner longitudinal system again render the apex a fixed point.
The opponent to the auricular musculature is the longitudinal
System passing to the auricular part of the A-V groove. There is
therefore the same to-and-fro movement here—the auricular mus-
sulature in auricular systole draws the ventricle up (from A—A’
Fig. 5), while by ventricular systole the A-V groove is drawn from
A —A, thereby expanding the left auricle and causing a negative
pressure. There should therefore be a rapid flow of blood from
the lungs to the left auricle during ventricular systole, but

THE HEART

there is no very positive evidence of this point, although the
tracings of the cardio-pneumatic movements appear to indicate
its presence.

From anatomical considerations, therefore, we come to the con-
clusion that the excitatory wave in its passage through the heart
travels from the parts representing the venous end of the primitive
cardiac tube to those developed from the arterial end. If this be
the case, evidence of this passage should be forthcoming from the
records obtained by different observers in regard to the electro-
motive phenomenon of the beating heart.’ Considerable discrepancy,
however, appears in such records. Waller and Reid found in

several mammalian hearts that the excitatory wave normally —

passed from apex to base. Bayliss and Starling, on the other
hand, observed the wave to pass normally from base to apex,

and only in the injured heart to pass in the reverse direction. |

Schliiter’s experiments on the cat’s heart appear to support Waller
and Reid. .

In view of this divergence of opinion the recent valuable
work of Gotch upon the frog’s heart is of great interest. His
records distinctly show that it quite depends upon which part
of the base of the heart the electrodes are placed as to what
form of curve is obtained. Normally, however, he is convinced
that the excitatory wave passes from the venous base of the
ventricle to the apex and thence to the aortic base in connection
with the great arterial trunks. Gotch’s results also show that a
high intracardiac pressure brings into prominence the action of
that part of the ventricle leading up to the aorta. This is there-
fore important confirmatory evidence of Keith’s view of the action
of the different sets of muscles in the ventricle:

When, too, we realise how small an area the A-V bundle in
the mammalian offers to the electrode, it is easy to understand
that contradictory results should be obtained for the mammalian
heart. There is every reason to suppose, therefore, that in the
mammalian heart also the excitatory wave follows the direction

of the primitive cardiac tube, and passes from the venous base —

to the apex, and therice back to the aortic base, ensuring thereby
an orderly sequence of movements. More work is wanted to

elucidate these movements and also many other points, the im- —

portance of which lies in the fact that “the heart... is the
beginning of life; the sun of the microcosm; . . . it is the house-

re . ; THE HEART
hol old divini Nidihy which, discharging its function, nourishes, cherishes, “'
anc quickens the whole body, and is indeed the foundation of life,
_ the source of all action ” (Harvey).

BIBLIOGRAPHY

GeNERAL Reviews witH ‘Extensive LITERATURE—

Burdon Sanderson, J., Schiifer’s Text-book of Physiology (1900), vol. ii.
p- 439.

Gaskell, W. H., Schiifer’s Text-book of Physiology (1900), vol. ii. p, 169.

Heinz, R., Handbuch der exp. Path, v. Pharmakol., vol. i. p. 638.
Gustav Fischer, Jena, 1905.

sis dag F. B., Nagel’s Handbuch der Physiol. des Menschen, vol. i.
_ p. 222. Braunschweig, 1905.

Langendorg, Ergebnisse der Physiol., Abth. II. (1905), p, 764.

PAaPERS—

Carlson, American Journ, of Physiol., xii. p. 67.

Erlanger, Journ, Exp. Med., viii. p. 8.

Fredericqg, Archives Intern. de Physiol., iv. p. 57.

Gotch, Proceedings of the Royal Society, B, Vol. 79 (1907), p. 323.

Heidenhain, M., Anat. Anzeiger, xx. (1901).

Hering, Pfliiger’s Archiv., eviii. p. 267.

Humblet, Archives Intern. de Physiol., i. 278; ibid, «lili. p. 330.

Imchanitsky, Archives Intern, de Physiol., iv. p. 1.

Keith, Journal Anat, and Physiol. xlii. p. 1

Keith and Flack, Lancet, August 11, 1906 ; Journal Anat. and Physiol.,
xli. p. 172.

Stassen, Archives Intern. de Physiologie, iii. ». 338; v. p. 61.

Schmidt-Neelsen, Archives Intern. de Physiol., iv.

Tawara, Das Reizleitungssystem das Siiugetierherzens. Gustav Fischer,
Jena, 1906. :

4

PULSE RECORDS IN THEIR RELATION TO THE
EVENTS OF THE HUMAN CARDIAC CYCLE

. By THOMAS LEWIS

THE study of the arterial pulse in man has occupied the attention
of physiologists and physicians for centuries. With the advent
of the graphic method, it yielded, at the hands of such investi-
gators as Marey (**), Landois (81), Mosso (°°), and a host of other
workers, results which have greatly enhanced our knowledge of
the human cardiovascular system. Not infrequently it has served
to stimulate research on problems of general and far-reaching
physiological significance, and in some instances has contributed
facts to our knowledge of the heart and arteries which it would
have been difficult to obtain from experiments on the lower
animals. The study of the human pulse carries with it a natural
advantage, which can hardly be overestimated; the subject of
experiment may be observed under normal conditions, and is
amenable to reason and more perfect control.

The examination of the individual curves of arterial sphygmo-
grams, upon which an incalculable amount of labour has been
expended, is, with the exception of a few instances, abortive in
yielding such information to the clinician as can bring him a pro-
fitable return for the time he expends. Empirical diagnosis from
pulse tracings is a method fraught with abundant and dangerous
pitfalls. It is for the evidence which the curves give of the events
of the cardiac cycle that they are to be chiefly valued, and it is
in this direction that the researches of modern, nay recent, years
have yielded such fruitful results. Above all, graphic curves taken
simultaneously from different pulsating points are invaluable, for
they accord information of the time relations and nature of the con-
traction of the separate chambers of the heart. The observations of
_ the past ten years, while supplying important physiological know-

72

PULSE RECORDS 73

ledge, bid fair to revolutionise the technique of cardiovascular
diagnosis.
Records can be obtained of the contraction of both auricles
_ and both ventricles in a large percentage of subjects. In certain
conditions the information so derived is of great service, for a
particular chamber may fail to contract, its contraction may be
imperfect, or it may enter upon its systole too early or too late.
Many irregularities of the heart have already received careful
analysis along these lines, and knowledge of much clinical import-
ance has been gathered in respect of them. In regard to one
affection of the heart, the pathological state now known as “ heart
block,” in which the path of conduction from auricle to ventricle
is disturbed or broken, and in which a slow pulse and its concomi-
tant symptoms constitute the chief features of the disease, a flood
of light has been shed upon a condition of which our ignorance
| was formerly profound. As to the therapeutic action of cardiac
| drugs, much work has been accomplished, and more remains to
|
:

be done. A wide field for study has been opened up which awaits
cateful and painstaking investigations ; and the day, it is hoped,
is not. far distant when the functions of the heart, and the
disturbances of the same, will be profitably referred to at the
bedside, in the terms employed by Gaskell in his well-known
researches.

But the study of pulsations in man can never reach that pitch
of mechanical perfection to which modern physiological experi-
ment has attained, and the conclusions drawn from the more
indirect observations on man must ever remain in a measure
subservient to, and controlled by, the more direct readings acquired
from animals. That emphasis should be laid upon this aspect

_ of the question is imperative, for there is a tendency to-day,
frequently noticeable in the consideration of human pulsations, to
fly in the face of physiological knowledge, which, as it is unques-
tionably of less fallacious origin, should guide, and form the basis
of, all conclusions.

In the: following pages the methods recently introduced for
the study of the cardiac cycle in the normal subject will be

examined ; a critical account will be given of the records obtained
in man; and the information so obtained will be compared and
brought so far as possible into line with the correlated knowledge

74 PULSE RECORDS IN THEIR RELATION TO
derived from the lower animals. In bringing together physio-

logical facts which may serve as an introduction to their clinical

application, pathological observations may be quoted only in so
far as they have a direct bearing on the several problems involved.
At the same time it must he noted that the boundary between the
physiological and pathological states has ever been broad, and
that so far as cardiovascular studies are concerned, recent observa-
tions have tended to its extension rather than to its limitation.
For the older conception of pulse irregularities as evidence of the
pathological state is no longer justified. Apart from the irregu-
larity, chiefly in the length of diastole, which, occurring as an
accompaniment of the respiratory movements, and dependent
upon vagal influences, is so familiar to physiologists, a closely
allied irregularity, termed by Mackenzie (**”) the “ youthful irre-

gularity” (p. 84), has been described as a normal event which ~

occurs at or about that epoch when the pulse diminishes in
rate and the heart takes up the rhythm which it will maintain
within narrow limits during adult life? Further it must be
recognised that spontaneous ventricular contractions* are of
common occutrence from time to time in individuals in whom no
further evidence of ill-health is available. These “‘ extrasystoles,”
though incompatible with our view of a heart functionating in an
ideal fashion, may be regarded with justification as consistent
with the indefinite borderland which lies ’twixt health and
disease. The frequency of their occurrence, in the otherwise

1 References to pages and figures allude to the bibliography, except where other-
wise stated.

2 Some of these irregularities are undoubtedly anomalous responses to respira-
tion (cp. Hering *); but it is equally beyond dispute that others have no
connection with breathing.

3 It is now generally acknowledged that the ventricular systole results from
a conducted stimulus proceeding from the auricle. But it is also recognised that
the ventricle may beat when this source of stimulus is removed. If at any time
this chamber contracts independently of the auricle, such a contraction may be
termed spontaneous. The origin of the stimulus giving rise to a contraction of
this nature is as yet imperfectly understood. There is reason to believe that it
arises in embryonic remains to which the function of rhythmicity is particularly
attributed. But for a further and fuller account of these autochthonous ventricular
beats, or extrasystoles as they are frequently designated, the reader is referred to

>

the works of Mackenzie (*¢) and Wenchebach (*), (The term ‘‘ extrasystole ”’ is a

here employed in its broadest sense. )

THE EVENTS OF THE HUMAN CARDIAC CYCLE 75

_ normal subject, over long periods, and more especially in associa-
tion with pregnancy, hard toil, or advancing years, brings them
into a domain, closely approaching, if not included within that of
physiology.

. Marey and his associates; Chauveau (*7) and Frangois- Franck (#4),
were amongst the chief pioneers of graphic records. The collected
observations of Marey, published in his books of 1863 (3*) and 1881 (3),
are comprehensive. In La circulation du sang, &c., are found
records of almost all visible pulsations of the normal human body.
Numbers of tracings taken from the healthy or diseased, experimental
observations, and records of apparatus combine to form a rich store-
house of facts, never equalled before or since, for the study of
hemodynamic problems. The apparatus figured, and employed in
the experiments, show an almost unrivalled wealth of ingenuity, and
many of the instruments in their original or slightly modified forms
are still in general use.

The methods of sphygmography are too well known to need de-
scription. Sphygmographs fitted with additional levers are numerous,
and serve in the procuration of simultaneous tracings from apex beat,
arteries, jugular vein, liver, fontanelle, or chest wall. The mechanism
used in clinical work upon the jugular pulse, the apparatus with which
we are chiefly concerned, is described later. The best receiver for
cardiographic records is perhaps Marey’s, consisting essentially of a
cup, covered by a rubber membrane to which a button is attached.
But a hollow uncovered receiver answers well for general purposes,
and may be employed over a less restricted field.

In animals the earliest work on intra-auricular and intra- ventricular
pressures was carried out by Marey’s school. Small rubber balloons
tied over the extremities of narrow metal sounds were passed through
jugular vein or aorta into the corresponding chambers of the heart,
and records of the pressures within these cavities were obtained by
connecting the metal tubing to tambours supplied with levers and
writing styles. It might be supposed that the introduction of such
sounds into the auricle or ventricles would seriously interfere with
their normal functions. This, however, is not the case. Chauveau
relates that he passed a double cannula of the sort, fitted with
balloons for auricle and ventricle, into the right heart of a horse,
without disturbing the pulse rate, or the meal of which the animal
_ was at the time partaking (Assoc. frang. p. Vavanc. d. Sciences, 1887).
The apparatus used by the earlier workers for the actual records

76 PULSE RECORDS IN THEIR RELATION TO

has undergone improvement. Many instruments have been introduced,
amongst which those of Hiirthle require special mention. The inertia
of the levers and membranes is reduced in Hiirthle’s instruments (?®)
to an almost negligible quantity. Air is replaced by fluid transmission,
for the compressibility of air renders it less reliable in obtaining records
free from extraneous movements. The delicacy and reliability of
Hiirthle’s instruments have been demonstrated by Bayliss and Starling
by a photographic method (3). Hiirthle’s differential manometer is so
constructed that two columns of fluid, each conveying the changing
pressures of a pulsating cavity, are opposed to each other. Any
difference in pressure in the two cavities is thus registered, and the
instrument is of particular value in ascertaining the instant at which
the pressures in two adjoining and communicating cavities, such as
auricle and ventricle, or ventricle and aorta, become equal. It is
with this instrument that information has been obtained in respect
of two “standard movements ” of the heart, namely, the opening of |
the auriculo-ventricular valves and the closure of the semilunar seg-
ments. The standard movements, to which further reference will
frequently be made, are of importance; they may be regarded as
fixed points of time, and it is convenient to describe and figure all
other cardiac movements, and oscillations to which these cardiac
movements give rise, in relation to them. The third standard
in common use is the commencement of ventricular systole, or
perhaps more accurately, the moment at which the pressure in the
ventricle commences to rise in systole. The onset of systole is an
instant which it is uot difficult to fix in animal experiments; but
in man, as will subsequently be seen, it is by no means so easy. It
is possible that with the further elaboration of Einthoven’s recently
introduced electrical method! more accurate indications may be
obtained. Einthoven uses a sensitive “string galvanometer” to
estimate the change of potential in the limbs, which occurs with
the heart beat. The observations, however, which have as yet been
made, have little bearing upon the subjects of this article.

In conclusion, the attempts instituted to obtain graphic records
of the heart sounds may be briefly referred to. Hinthoven
and Geluk (®) employed a microphone and capillary electrometer.
Hiirthle (26) also used the microphone for a similar purpose. Obser- -
vations which are referred to in the text have thus been carried out
on the instants of onset of the first and second sound ; but given more

1 Archives Internat. de Physiologie, vol. iv., 1906-7, pp. 132-164; Archiv.
7. d. ges. Physiol., Bd. 122, 1908, s. 517-584.

‘THE EVENTS OF THE HUMAN CARDIAC CYCLE 77

‘convenient and reliable instruments, many problems of no inconsider-
able clinical significance would receive elucidation. There is no
question that by assiduous training a clinician with keen perceptive
faculties may acquire great skill in timing and interpreting abnormal
heart sounds. Yet the dogmatism of the present day upon the sub-
ject of heart murmurs is entirely unjustified, a conclusion which is
completely borne out by the inconsistent yet equally peremptory
opinions of independent observers of. the same subject. Franck} in
a preliminary communication has recently described a new instru-
ment, based on the principle of the middle ear, with which graphic
records may be taken. Einthoven? has successfully used his galvano-
meter for the same purpose. Further results are awaited with
expectancy, for there is every possibility that the apparatus may
supply a long-felt want.

I. THE VENTRICULAR CYCLE AND THE STANDARD MOVEMENTS

The interpretation of the time relations of the human ventri-
cular movements at present *® depends on cardiographic tracings,
complex curves involving changes of pressure, volume and
diameter in the left ventricle, and the errors emanating from
this method must constantly be borne in mind. It is probable
that the shock of the apex beat gives in thin-walled chests a
fair approximation of the onset of systole, with an error which,
though difficult to state accurately, probably does not exceed
‘02 sec.*

? Otto Franck, Miinchener mediz. Wochensch., Bd. 51, 1904, s. 953. Weiss _
and Joachim (Pfliiger’s Archiv., Bd. 123, 1908, s. 341) have more recently
succeeded in obtaining numerous records of heart sounds and murmurs which
appear to be of considerable value,

® Pfliiger’s Archiv., Bd. 117, 1907, s. 461.

% Eventually it will probably be controlled by electric curves.

“In one of Hiirthle’s tracings () (Fig. 7) there is an exceptional difference
of -06 sec. between the upstroke of the cardiogram and the registration of the first
sound. In animals the tracings of Chauveau and Marey (7), Roy and Adami (**),
Hiirthle (™), and most other writers show the upstroke of ventricular pressure and
cardiogram to be synchronous ; but such tracings are taken under exceptionally
favourable circumstances. x

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THE EVENTS OF THE HUMAN CARDIAC CYCLE 79

TABLE II
Delay from | Delayfrom!| Velocity, Velocity, | Velocity,
AUTHOR, Aorta to | Carotidto | Carotid to Aorta to Aorta to
Carotid. | Radial. Radial, Radial. | Carotid

Landois . : ‘ ee vs er 5°7 m.p.s. a |
Keyt. : ; ‘ ‘0279 ‘0797 7-9 m.p.s. sat: —
eee ae
Edgren . ‘ ; 026-7 ‘0792 nae 8 m.p.s. ws |
-|—_|___

_| Griinmach (%) . : 03 06 3 9m.p.s, | 6°6 m.p.s

Martius. : - 03 |
Hirthle () - | 03 er ey +e | 6 m.p.s.

The terms employed in Table I. require brief definition. It must
not be forgotten that the curves of intra-ventricular pressure cannot
be taken as indicative of the changes in the volume of the ventricular
blood content. When the ventricles contract and the pressures in
them augment, their blood content remains unchanged, for no blood
leaves them until the pressures rise to aortic and pulmonary pressure.
The interval which elapses in this way, prior to the raising of the
arterial valves, constitutes what is termed the “ presphygmic ” in-
terval. But the pressures in the arteries begin, and those of the
ventricles continue, to rise subsequent to this interval; this continued
rise in the ventricles is consequently spoken of as the “ period of rising
arterial pressure.” Following upon it is the plateau, indicated in the
pressure curve by a wavy line, which runs horizontally, or slopes
slightly upwards or downwards. During the whole of this plateau
the volume of the ventricles is decreasing and blood is leaving them;
but as it leaves them at a lessened rate, it does not, necessarily, further
raise the arterial pressures.

At the end of the plateau, the pressures in the ventricles fall, and
when they are reduced below the arterial pressures, the pulmonary
and aortic valves close. It is, however, a little while before the pres-
sures fall sufficiently to allow the auriculo-ventricular valves to open,
and this interval is often spoken of as the “ postsphygmic ” interval.
Following upon it there is a pause, during the whole of which the

80 PULSE RECORDS IN THEIR RELATION TO

ventricles are expanding and receiving blood from the veins and
auricles. The term ventricular diastole is usually loosely applied,
and has been avoided in the table; we have not sufficient knowledge
of the period over which the ventricles are expanding actively, if they |
ever do so, to define the time limits of diastole with precision. .

In referring to the accompanying tables mention must be
made of observations recently carried out by Erlanger (?°) and
Tigerstedt (*’), the results of which are included. The estimates
were made from subjects in whom there were partial defects of
the chest wall and in whom the heart was readily accessible. The
figures are probably as accurate as any we possess; Keyt’s
numbers (”), dependent on numerous and elaborate measurements,
compare well with them. The figures given in the first table are
taken as far as possible from young adult subjects, and the delays
and velocities exampled in the second table are illustrative of |
normal pulse rates. Some figures from a tracing after Hiirthle (7*)
(Taf. III., Fig. 12) are also given for the comparison of man and
the dog. No such estimates are absolute ; there is a wide varia-
tion with numerous factors, such as pulse rate and blood pressure.

But though eventually the cardiographic upstroke is the
standard movement on which the chief measurements are based,
in clinical practice the frequent absence or inversion of the apex
beat renders it unreliable, and it becomes necessary to fix further
standards. For this purpose the carotid pulse is chosen as the
safest and most useful guide. Its utilisation involves under many
circumstances a calculation of the presphygmic interval, and the
normal transmission delay of the pulse wave from the semilunar
valves to the carotid. In the normal subject the presphygmic
interval may show variations of at least 03 séc., with age, pulse,
rate, &c. In disease it may amount to as much as ‘06 sec. In
clinical application, in which relatively slow travelling recording
surfaces are used, an error of less than ‘05 sec. is as a rule
negligible, and the figure ‘05 sec. may be taken as a comparatively
secure working estimate of the presphygmic interval. The error
entailed in calculating the transmission delay from aorta to carotid
is probably not greater than ‘01 sec. in health and ‘03 sec. in
disease ; the interval may be taken for clinical purposes at ‘03 sec.*

1 Weiss and Joachim have recently measured the interval between the first

heart sound and carotid pulsation in man (Pfliiger’s Archiv., 1908), and find it as
a rule ‘08 to °09 sec.

°

THE EVENTS OF THE HUMAN CARDIAC CYCLE 81

n jugular tracings are taken simultaneously with a standard
1s Remnant, the radial pulse is usually employed on account of
‘its convenience. This method involves a third error, the variation
in transmission delay from the aorta to radial vessel. The varia-
tion in this delay is so great, and the accumulated error becomes
80 magnified, that it is unsafe to fix the radial pulse as the
standard movement if the carotid to radial delay is not first
estimated and allowed for in the particular case.’

The determination of the position of closure of the semilunar
valves (S.C.) and of the opening of the auriculo-ventricular
valves (A.O.) upon human cardiographic and carotid curves pre-
sents considerable difficulties.

In. animals it is now held that the S.C. point occurs a short

distance along the downstroke of intra-ventricular pressure
(Hiirthle (*), Porter (*°), Bayliss and Starling (3), &c.).
point is found in simultaneous tracings to correspond on the aortic
curve to the bottom of the dicrotic depression (aortic notch) ; *
on the carotid tracing, which is slightly delayed, it falls at or
about the beginning of the same depression. On the cardio-
graphic curve it corresponds in animals to a point near the end
of the ventricular plateau; thus Marey (*”) (Fig. 40) places it
before the end of the plateau, Hiirthle’s tracings (7) show it before
or slightly after the end of the plateau. To sum up, there is no
constant relationship between cardiographic and intra-ventricular
curves at this phase.

In man the 8.C. point is placed by Edgren (°) at the bottom
of the cardiographic downstroke, at a point indicated by a small
wave. According to Hiirthle (*”) it is situated in the first third of
the downstroke, and it is placed at the same instant by Einthoven
and Geluk (*), despite the fact that they were guided by the record
of the second sound, which occurs later than the closure. The
~ method in which the second sound is marked on the tracing by a
signal worked with the hand, allowance being made for reaction
ime, is obviously unreliable and gives varying results (cp. Edgren’s

-

af
5

3 1 The figures given and statements made are the result of a critical examination
fa large number of statements and tracings. The space at our disposal prohibits
full examination of the facts. There is a good deal of divergence between the
¢s given by different authors, and further work giving more detailed analysis
be of much value, for at present general statements are of necessity very

DX UT

82 PULSE RECORDS IN THEIR RELATION TO

tracings). As the cardiographic curve in its relationship to the
second sound in man shows no constancy, and as it shows a
similar divergence when compared at this phase to the carotid
curve,! it cannot be regarded as a safe criterion in fixing the 8.C.
point. The constancy of the relationship of the S.C. point to the
aortic curve in animals shows the necessity of taking the carotid
curve as the standard in man. The nearest approach to accuracy
is obtainable by allowing for the transmission time from aorta to
carotid. The S.C. point in man is thus fixed at a point ‘03 sec.
in advance (to the left in Fig. 1 of this article) of the bottom of the
dicrotic depression.

The actual determination of the A.O. point in man is im-
possible. In animals most writers are agreed in placing it at the
bottom of the intra-ventricular downstroke.? On the aortic curve
it is marked at the summit of the dicrotic (Porter, Hiirthle, Bayliss
and Starling). Cardiographic curves show no constant relation-
ships at this phase. In man the A.O. point is best fixed on the
carotid tracing, ‘03 sec. in advance of the summit of the dicrotic
wave. It is to be noted, however, that this introduces a possible
source of fallacy. Galabin® states (1°) that the dicrotic summit
recedes from the apex of the primary wave as the pulse travels
along the vessels. The error from this alteration is probably so
small as to be quite negligible in the carotid tracing, but it con-
stitutes an important element in radial tracings, which should
therefore never be employed in estimating this point, in exact
work. It must.not be forgotten that the A.O. point in man is the
_ most difficult of all the standard movements to ascertain ; conclusions
drawn from it must always be received with due caution.

II. THe RELATIONSHIP OF THE AURICULAR AND
VENTRICULAR CYCLES

(a) The Evidence obtained from Intra-auricular Curves
in Animals.—The events of the auricular cycle have received

1 Thus in Keyt’s tracings the bottom of the cardiographic downstroke corre-
sponds on the. carotid to the bottom of the dicrotic depression, or to a point on the
upstroke of the dicrotic itself. In Edgren’s tracings, as in Hiirthle’s, it is placed
as a rule at the bottom of the depression; but there is very considerable divergence
in the individual curves of these authors.

2 Estimated by differential tracings. ;

8 The statement of Galabin is supported by many of the tracings which
Keyt gives. The question is discussed by Frey (Untersuch. d. Pulses, 1892).

~ cies

‘THE EVENTS OF THE HUMAN CARDIAC CYCLE 83

careful investigation at the hands of Chauveau and Marey, D’Es-
pine, Fredericq ("*), Frey and Krehl (#*), and Porter. Recently
‘Hering (***) has studied the same subject, using the perfused heart ;
-and further observations have been made by Rautenberg (*”).
_ For the most part the experiments have been on dogs ; those of
‘Chauveau and Marey were carried out on the horse.
The curves given by Porter are perhaps as much in accord

with the general evidence as any, and it will be found convenient

to take these as typifying the changes in intra-auricular pressure,
eventually examining the results of experimental work in relation
to such a type. In common with all other observers Porter found
that auricular contraction is accompanied by a positive wave
of pressure. At or a little before the termination of auricular
‘systole this “ first positive wave ” * gives place to a “ first negative
wave,” a wave which, but for the interposition of the, ‘“ second
positive wave,” forms with the “second negative wave ” the main
depression of auricular pressure during the cycle. (A curve illustrat-
ing the waves and their relation to the curve of intra-ventricular
pressure is given in the accompanying figure, Fig. 1). The second
positive wave, which breaks this otherwise steady fall, is said by
most writers on the subject to occur at the onset of ventricular
systole, and is usually figured as lasting until the point which marks
the opening of the semilunar valves.* The wave is well shown on
the tracings of Chauveau and Marey, D’Espine, Fredericq, Porter,
_and Rautenberg, but it is absent from those of Frey and Krehl.
Porter (p. 526) noted its absence on occasion. Fuller details of
its significance will be discussed later. Relaxation of the auricular
wall is stated by Porter to last to the beginning or end of this
wave. The point at which the second negative and “ third posi-
tive waves” meet is at present the subject of considerable dis-
cussion. Chauveau and Marey placed it at the end of ventricular
systole,* but otherwise there appears a consensus of opinion,
1 Cited by Frederieq (™, p. 524 and Fig. 19).
* In the auricular tracings given by Porter there are in all three main elevations
i three main depressions. The terminology of the curves is at present so cOn-
— the employment of Porter's original designations is impossible. In the
g pages the rises and falls will be spoken of as the first, second, and third
‘ive, ‘and the first, second, and third negative, wave respectively.
% "3 estimated by means of differential manometer tracings (Hirthle
x ie tae stacing given in the Gaz. méd, d. Paris, 1861, p. 673, the second positive

a s not shown, and the third positive wave commences during the systolic

a
Fi

ae

84 PULSE RECORDS IN THEIR RELATION TO |

amongst those who have taken auricular pressure curves, that it
occurs earlier (Frey and Krehl, Fredericq, Porter, Hering, and
Rautenberg). While it may probably be placed with a fair degree
of certainty in the middle or last third of the systolic plateau,
there is every possibility that it is subject to variation. The
third positive wave ends in the “third negative wave” during
ventricular relaxation. Generally the point is given at the bottom
of the falling ventricular curve, the instant at which is placed the
opening of the auriculo-ventricular valves.!_ Porter himself figures
it at a slightly earlier time interval,? at a position in the cycle
recognised as representing the closure of the semilunar valves,
namely, a short distance after the end of the systolic plateau.

(b) The Venous Pulse in Animals and Man.—Pulsation
of the veins of the neck in pathological conditions is often such.
an obvious phenomenon that it must have been recognised for
many centuries. References to venous pulsation can be traced
in the writings of Lancisi (°°, p. 182) and Morgagni (**) in the
early and middle years of the eighteenth century. In 1794
Hunter described pulsation in the veins of a dog; but it is ques-
tionable if these writers appreciated the extent of the movement ;
their observations appear to have been confined to the veins in
the immediate neighbourhood of the heart. Later, similar move-
ments were described by Weldemeyer (8) in the veins of a horse.*
Friedreich (14) took venous curves from the neck of pathological
subjects in 1865; and two years later Potain (*°) obtained simul-
taneous tracings of the apex beat, carotid, radial and jugular
pulses in the normal human subject, and his description of the
events and his interpretation of them are,’ in the light of our
present knowledge, wonderfully accurate. From the time of
Potain’s contribution, observations have been published by many _ |
writers, amongst whom may be mentioned, Mosso, Gottwalt (1%),

plateau ; the tracings repeated in Marey’s book show the second positive wave, and
the third positive wave occurs at the close of systole. The collected curves given
by Chauveau in 1887 (Assoc. franc. p. l'avane, d. Sciences) are very various, but
as a rule show the three chief waves distinctly.

1 The point is estimated by differential pressure tracings,

2 Porter’s curves were from the left auricle, and show, like most others, some —
variation in their last phases.

3 For full historical accounts the reader is referred to Mackenzie's earlier \
papers, and the recent xt pabBowtio of Baum (?). /.

°

THE EVENTS OF THE HUMAN CARDIAC CYCLE 85

Riegel (*), and Frangois-Franck (")._ In 1893-4 Mackenzie (***)
published his first papers, which, with his collected observations on
“The Study of the Pulse,” appearing in 1902, have given the
impetus to a careful investigation of the whole subject.

Pulsation in the veins of animals is not confined to the larger
vessels feeding the auricles ; it is a constant phenomenon in dogs,
cats, and rabbits, and may be seen extending in many of them
into the smaller veins of the neck and limbs. Gottwalt was of
opinion that the jugular veins of all normal persons pulsate, and
this conception is receiving constant confirmation. ‘It is possible
at the present time to obtain venous records from the neck of a
large percentage of normal individuals ; Wenchebach states that
it is feasible in most subjects, healthy or diseased. Pulsation is
frequently so well marked as to be visible, and in thin or anemic
subjects often constitutes an obvious movement. It is highly
probable that with improved apparatus curves will be invariably
obtainable... Any agency which tends to promote a heightened
venous pressure, such as raised intra-thoracic or abdominal pres-
sure, or gravitation, increases the force and visibility of venous
pulsation. It is for this reason that tracings are best taken
in the reclining posture, and that in those cases, where pulsation
is feeble, expiratory suspension of respiration increases its
prominence.

In man, the venous pulse is seen and recorded with the greatest
facility in those veins which have but a short distance to travel
before reaching the heart. A special and valuable anatomical
description of the veins of the neck in relation to this subject has
recently been given by Keith (?§). Tracings may be taken direct
from the external jugular vein when this is engorged, but more
often the receiving instrument must be applied to the jugular
bulb, which lies a little above and 25 mm. external to the sternal
end of the clavicle.* A needle passed back into the neck at this
_ point strikes the internal jugular vein at a point where it is
guarded by a pair of valves, which, when the path to the auricle
_is obstructed, or when blood is regurgitated, produces a bulging
in the vessel from which the “ bulb” derives its name. Passed
further on the needle transfixes the subclavian artery. Tracings
1 If they are not already.

_ * The receiver should be as a rule applied between the two heads of origin of
shi sterno-mastoid muscle.

>

86 PULSE RECORDS IN THEIR RELATION TO

are obtained from the neck, in which the sterno-mastoid is relaxed,
by applying to it with light pressure a small receiver, whose width
is about 4 cm., and depth 1 cm.! The interior of the shallow
cup communicates with a delicate tambour carrying a writing
style. This simple apparatus is perhaps the most satisfactory as
yet employed. The accuracy of its records has been checked by
Mackenzie, its originator, and by Gerhardt, by comparisons with
the tracings given by light levers directly attached to the skin
overlying a superficial vein; and the movements of the recording
tambour and lever, so far as the main waves are concerned, have
had their reliability checked by comparison with the tracings
yielded by a Hiirthle manometer (Gerhardt). Air transmission is
employed, and the curves obtained from the jugular bulb are
frequently complicated by the primary wave of the carotid pulse,
which in clinical work is not without its advantages, and by the .
respiratory movements when these are present. Curves are best
obtained from the right side of the neck, for here the course of
the innominate is shorter and more direct from neck to heart
(Friedreich, p. 282); clinically they may also be taken from the
pulsating liver.

With regard to the rest of the mechanism little comment is
necessary ; when the apparatus described is adjusted to a modified
Dudgeon sphygmograph, as in Mackenzie’s original instrument, the.
fitting of a reliable time-marker renders it cumbersome. Another
convenient instrument for clinical work is ‘“‘ Mackenzie’s ink
polygraph,” 2 with which tracings of any length and at various
speeds: may be taken. It allows a simultaneous record of any
two given pulsations, and carries a reliable time-marker. The |
curves from the jugular vein give, considering the indirect methods
of determining them, surprisingly constant results, and in this lies
their chief justification.

1 There is a tendency, not without its advantages, towards the use of smaller
receivers. si

2 The apparatus, an account of which is published in the British Medical
Journal for June 13, 1908, p. 1411, is open to improvement; more particularly
the writing styles, and that portion of the mechanism used for the record of the
radial pulse. The momentum of the levers and membranes is considerable, and
extraneous movements cannot be entirely excluded. For the interpretation of the _
main waves it answers its purpose admirably, but for the investigation of me minor
waves more delicate apparatus would be requisite.

It is necessary to insist on the disuse of time markers whose movement depends
on the clockwork which drives the paper.

‘THE EVENTS OF THE HUMAN CARDIAC CYCLE 87

In animals curves have been secured from the vein wall
or blood stream, by Gottwalt, Frangois-Franck, Morrow (*’),
Fredericq (?*°), Rautenberg (*°), and others. The results in man
and animals are in such general agreement that one description
_ of them will suffice.

Speaking broadly, the venous pulse, like the auricular curve,
shows three main elevations and three main depressions ;! the
general outlines of venous and auricular curves are such as to
leave no reasonable doubt that the factors ultimately concerned
in the production of their waves are identical for each, a relation
on which many writers have laid emphasis. The final evidence
depends on the detailed analysis of each wave of the curves and
will be undertaken subsequently. For the time being it will be
convenient to recognise the three main elevations of the venous
curve (the “a,” “c,” and “v” waves of Mackenzie) as corre-
sponding to the three positive waves of the auricular pressure curve,
and ye three main dips of the venous tracing (the “x,” “x’,”
and “ y” depressions of Mackenzie) as corresponding to “the three
chief cA es waves of the auricle. These events are represented
in the accompanying figure (Fig. 1), and their relations may be
tabulated as follows :—

oe Slee ; : , . First positive wave.
oh ates é : , . First negative wave.
Sor 34 ; ° ‘ . Second positive wave.
whe tage , ; . . Second negative wave.
iy: i : ; . Third positive wave.
bby? ird :

: ile : : ; . Third negative wave.

The waves of the jugular pulse have not received such an
_ accurate comparison to standard movements as have the auricular
in animals. This is but natural, for with the indirect
methods available the sources of error are comparatively large,
and little advantage is to be gained by the use of more rapidly
travelling recording surfaces. But writers are in the habit of
expressing themselves dogmatically as to the time instants. at
which certain events are taking place, while at the same time
they appear to lack a due appreciation of the comparatively rough
‘methods by which the standard movements of the cardiac cycle
fixed in man. Cardiographic curves are notoriously uncertain,

1 A record of the venous pulse is shown in Fig. 3, at the end of this article.

88 PULSE RECORDS IN THEIR RELATION TO

-14 05 0503 22

"4

06 }03 *37 Secs.

S.C line) |
line.

tie
}
5
/]

2h Pes.
Pos.

Pou
HA
As *
.
P
‘
“ ¥] as, 3
3
PA
oe

Fic. 1.—Diagrammatic representation of the events of the cardiac cycle and of
the carotid and jugular pulses in relation to standard movements. The scale ©
of abscissee is 1 mm. to x}, sec. §.C.=semilunar valve closure; A.O.=auriculo-
ventricular valves open. The broken lines indicate those geese of the respective
curves over which there is doubt or controversy.

THE EVENTS OF THE HUMAN CARDIAC CYCLE 89

and carotid tracings must be judged on their merits. The dis-
crepancies in the findings are greater in the case of jugular curves
than they are in the case of the auricular. Considerable confusion
appears to exist as to the events occurring in that portion of the
heart’s cycle which lies between the closure of the semilunar valves
and the opening of the tricuspids. Further work is needed, and
the first appeal must obviously be to experiments upon the time
relations of the venous curve in animals. But though there are
differences of opinion, it must be understood that they are in the
main of a minor character, and their complete elucidation is
chiefly necessary that the origin of the waves may be accurately
determined. The differences which have so far arisen are, in
other words, of such a nature as to in no way invalidate the
information which can be obtained at the bedside.

The majority of writers are agreed in timing the commence-
ment of the “c” wave in man as synchronous or almost syn-
chronous with the primary wave of the carotid at the same level
of the neck. Fredericq ('°), moreover, has recently shown them
to be simultaneous in the carotid and jugular of the dog. For
practical purposes the two waves may be taken as starting
together, but the actual evidence for their absolute synchronicity
is perhaps not convincing. In certain instances Fredericq found
a slight deviation, and Bard (?”) has obtained similar results
in man.!

The “a” wave and “x” dépression have together a duration
of 4 to 4 sec. (Mackenzie, Gibson ('*), and many other writers),
and constitute the a-c interval. This a-c interval, the time dis-
tance between the beginnings of the waves representing the com-
mencement of auricular and ventricular systole, is taken as a
measure of the function of the heart in respect of the conduction
of impulses from auricle to ventricle, and is of great clinical
importance.

Over the relations of the “v” wave there is some difference
_ of opinion, and this apparently for several reasons. In the first
place, it shows considerable variation in form; it may show a
division into two; it assumes an entirely new outline and new

1 Bard’s tracings (?») are not beyond criticism. It is not expressly stated that

jhe jugular and carotid curves were taken at the same level in the neck, and the
deviation might be attributable to transmission delay. Professor Bard has recently
ublished further notes ('*) on this subject. Bachmann has confirmed his results
Amer. Journ, Med. Sci., vol. 136, 1908, p. 674).

90 PULSE RECORDS IN THEIR RELATION TO

time relations in conditions where there is engorgement of the
right side of the heart. Secondly, different writers refer it to
different standard events, which constitutes a wide source of
error, and but rarely indicate the evidence from which the stan-
dards are derived. Thirdly, it is frequently impossible to be certain
whether writers are referring to the actual time relations of the
events, or whether a phase of the “v” wave is attributed to a
particular ventricular movement. It so happens that a definite
statement of the relationship of the “v” wave to a standard
movement is not of common occurrence. The collected evidence
as to the time relations in the normal subject is so involved that
it is impossible to consider it in detail. It is held by the majority
that the wave commences during the systolic plateau. Gerhardt ("*)
and Wenchebach consider that it is a purely diastolic event.
Gerhardt times its occurrence with the commencement of the .
dicrotic wave; and Wenchebach finds it synchronous with a
notch on the downstroke of the cardiogram. The evidence of the
tracings of individual writers is nevertheless in favour of the
view that the point of commencement is subject to variation, and
that it may commence during the plateau or near its termination.
Its termination in the “y” depression is universally stated to be
synchronous with the opening of the auriculo-ventricular valves.
The evidence for this last relationship does not appear to be so
conclusive as one might expect from the statements made on the
subject. Thus in Mackenzie’s tracings the point as a rule corre-
sponds to the bottom of the cardiographic downstroke,! while in
certain of those of Wenchebach (as in Figs. 6 and 7 of his paper),
it starts at a point distinctly later. A critical examination of
the subject reveals many sources of fallacy, and the majority of
tracings are taken on comparatively slow-moving surfaces, so that
the error in marking the points is large. Later when cesophageal
tracings are discussed it will be seen that the fixation of the “y”
depression at the A.O. line involves an obvious discrepancy.

Other waves have been described on the venous tracing; a
positive wave preceding the “a” wave (Gibson and Ritchie’s
sinous wave |’); a positive wave between “a” and “c” (Bard’s
accident inter-systolique '*); a fourth positive wave following “v”
(Morrow’s second outflow wave *°).
opinion on the subject, and these waves cannot be regarded as

1 Or to the bottom of the dicrotic notch. Potain and Gottwalt agree.

There is no unanimity of —

THE EVENTS OF THE HUMAN CARDIAC CYCLE 91

_ fundamental and constant, or at present of any great practical
significance. It would be premature and unprofitable to discuss
them.

(ce) The Evidence obtained from Intra-cesophageal Trac-
ings.—By means of an cesophageal bougie, fitted with a small elastic
balloon, tracings have been obtained from the heart, which are
not without value. The auricular curves are from the left auricle,
which lies in contact with the gullet. They are to be used-with
caution, for they suffer in a measure from the same defect as do
cardiographic curves; it is not possible to say to what extent
they are volume and to what extent pressure curves. Moreover
they show considerable variation according to the level at which
the balloon is placed (Young and Hewlett®’). In dogs such
tracings were obtained as early as 1888 by Fredericq, and.recently
Minkowski (*5), Rautenberg (****), Joachim (*’), Young and Hewlett,
and others have secured them in man. The tracings are in the
main in fair agreement, and show curves similar to those of
intra-auricular pressure in animals. Disagreement, however, has
arisen over that portion of the curve representing auricular
contraction.

According to the earlier observations, auricular contraction is
indicated by a depression in the tracing, whereas Rautenberg (***),
in all tracings but one (Fig. 5), attributes a convexity to the same
event. °

Now cardiographic curves from the ventricles, when taken
from any other point than the apex of the left ventricle, show a
curve which is roughly an inverted picture of the intra-ventricular
_ pressure. In one respect the picture shows no inversion, the
auricular wave when present retains its intra-ventricular form.
Briefly, those portions of the curve are inverted which are de-
pendent on active movements of the ventricular wall. In the
same way it would be expected that when intra-auricular and
cesophageal curves were compared, those portions of the ceso-
phageal curve would show inversion, which were independent_of
ventricular movements. The curves as interpreted by Fredericq,
Joachim, and Minkowski fulfil this expectation; Rautenberg, on
the other hand, finds as a rule no inversion of any part of the curve.
As Hering states, it is difficult to understand how a contracting
left auricle can raise the cesophageal pressure, at a point at which

92 PULSE RECORDS IN THEIR RELATION TO

this chamber is alone in contact with the gullet. Rautenberg
has attempted to defend his position by taking tracings in animals
from the cesophagus, simultaneously with others from the right
auricle, the apex beat or jugular vein. But his tracings do not
offer convincing evidence, and necessitate the assumption that the
apex beat is long delayed, an assumption which is not borne out
by the simultaneous tracings from apex beat and cesophagus. It
must be admitted that the auricular contraction may give a
negative curve, and if at the same time it is to be recognised that
a positive curve may result, the possibility of intermediate types,
half negative and half positive, introduces serious difficulties into
the interpretation of the tracings. The same problem arises in
the case of those curves obtained

ab G from the auricle through the chest
PNY wall. Erlanger’s curves taken from .

the auricle, and already referred to,

show the auricular waves inverted,

eed while Rautenberg’s curves (#4) re-

H . . . .
Sa corded in a similar manner are in-
Fic. 2. terpreted as showing a convex wave.

Here again there is the necessary
assumption of delay in the appearance of the apex beat, some-
times amounting to‘lsec. An illustration (Fig. 2 of this article),
based on one of Rautenberg’s curves (***) (No. 2), will make this
point clearer. The upper curve is from a point on the chest wall
overlying the right auricle; the lower curve is from the apex
beat. Four corresponding points have been marked on the
curves, the upper of which is open to two interpretations.
According to Rautenberg, auricular contraction is represented
by a-c, and there is a delay, c—d, between the commence-
ment of systole and the upstroke of the cardiogram. On the
other hand, it may justly be argued that the contraction of the
auricle is represented by b—d, and that the curve is inverted ;
and this view receives confirmation from two sources. In the first
place, other observers do not find delays in the upstroke of the
cardiogram of a nature comparable to those given by Rautenberg ;
and secondly, Rautenberg’s cardiographic curve itself shows a rise
which can only be attributed to the auricular wave, namely, at 0.
In view of the argument which might be raised, that the auricular
wave is delayed, it would perhaps be safer to await further work

THE EVENTS OF THE HUMAN CARDIAC CYCLE 93

before pronouncing a definite opinion as to the time relations
of the auricular contraction as represented in esophageal
curves ; and this the more as the example given is one of the
most simple.

It is requisite that the delay in onset of the “a” wave in the
neck should be definitely ascertained, but at Febiets the data are
insufficient."

(Esophageal curves show the second positive wave with great
constancy (Fredericq, Joachim, Minkowski, Rautenberg, and
Young and Hewlett), and its onset is said to coincide with
ventricular systole. Young and Hewlett, and Rautenberg agree
in showing that it occurs on these curves earlier than the “c”
wave upon the jugular tracings. According to the former, the
delay ® is ‘1 sec. ; according to the last named, ‘079 sec.* (average
of six observations). The necessity of fixing the time difference be-
tween the second positive and the “c” wave will be obvious when
the following facts are taken into consideration. As we have seen
the a-c interval is of great clinical importance, and is usually of
‘2 sec. duration as recorded with the polygraph from the jugular
vein in the neck. Such evidence as we possess tends to show that
the time difference between the onset of auricular and ventricular
contraction, as registered by cesophageal and direct auricular curves
in man and animals, is less, and amounts to little more than ‘1
sec. The difference in the two figures can only be accounted for,
assuming them to be correct, -by the quicker appearance of the
“a” wave in the neck. |

In cesophageal tracings a third positive wave is present. Here,
as in the case of the “ v ” wave, opinion is divided as to its moment
of onset. Minkowski finds that it commences with the second
sound; Young and Hewlett represent it as commencing in the
middle of the ventricular plateau, and ending at or a little before

1 The electrocardiogram taken simultaneously with the jugular curve should give
a speedy answer to this question. A few such curves obtained by the author show
a delay of approximately ‘08 sec. (For which see appended note and Fig. 3.)

2 It is necessary to anticipate the discussion of the identity of the two waves.
The full evidence will be considered later. =

* The figures are in agreement with other values, for allowing ‘05 sec. for the —
_ presphygmic interval and ‘03 sec. for transmission from aorta to carotid or sub-

clavian, we obtain a delay in the arterial shock of -08 sec
* Einthoven's electrocardiograms show an interval varying from -1 to ‘2 sec.
between onset of auricular and ventricular — change. The average is about
“14 sec. in man.

94 PULSE RECORDS IN THEIR RELATION TO

the opening of the auriculo-ventricular valves. In these par-
ticulars as to the positive wave the curves of Rautenberg agree
in that the third negative wave starts at the end of the plateau.
According to Young and Hewlett the wave occurs ‘1 sec. earlier
than the “v”’ wave in the neck, and they attribute much of the
confusion which has arisen in its interpretation to a neglected
consideration of this delay. Rautenberg finds a delay both in
man and animals; the average of observations on six human
subjects gives the figure at ‘081 sec.

If the diagram (Fig. 1) is again referred to, the discrepancy
mentioned at the end of the last section will be understood. The
majority of the intra-auricular pressure diagrams show the third
negative. waye as commencing at the A.O. line. If the “y”
depression is fixed at the same point, no delay is allowed for. For
this reason a curve more nearly corresponding to those given by
Porter of intra-auricular pressure is also introduced. If the
third negative wave is regarded as terminating on the A.O. line,
it becomes necessary to move the “y” depression to a position
indicated in the figure by the broken line, marked +.

In connection with the delays, it is important to note that
transmission of pressure waves in the venous channels is slower
than in the arterial, for the tension is less in them, and the waves
travel ‘against and not with the stream. Young and Hewlett
estimated the rate of transmission in a case of tricuspid failure
at 1:2 m. per sec. Rautenberg’s figures indicate a transmission
velocity of 1:5 m. per sec. Morrow found in animals a variation
in velocity from 1 to 3 m. per sec.”

The main conclusions to be drawn from cesophageal curves
are, first, the similarity of intra-auricular curves in man and
animals ; and secondly, the fact that the separate waves of the
jugular pulse show an appreciable delay in transmission from
auricle to neck.* They are also of importance in providing a

1 A point estimated apparently as half way down the downstroke of the cardio-
gram. It frequently happens, as in this instance, that the evidence upon which
this standard instant is timed is not fully stated.

2 The rate of transmission of the several waves is not of necessity the same. As
will subsequently be seen, it is improbable that they are all of the same nature.

° Of further conclusions which have been drawn, there is one which deserves
notice. Joachim and Rautenberg have shown in certain cases of heart block that
right and left auricles beat in unison. The statement is only approximately true

and applies to clinical work. Some recent observations may be quoted: in this
connection. Stassen (**) finds that the right auricle in dogs contracts °02 sec.

‘THE EVENTS OF THE HUMAN CARDIAC CYCLE 95

‘means of recording the movements of the left auricle. As a
routine practice the method is naturally impossible, and con-
traction of the left auricle is also frequently represented on the
cardiographic curve. In this connection it is of interest to notice
that the auricular wave in the cardiogram often shows a shortened
duration, as does that in the cesophageal, when compared to that
in the jugular.

The evidence so far considered has led to certain aaa
as to the time relations of the events of the cardiac cycle in the
normal human subject, and these conclusions have been incor-
porated as carefully as possible in the figure given on page 88.
The subsequent discussion will be based to a large extent on the
assumption that the events are correctly represented, That they
are approximately correct is beyond doubt, but that they are
rigidly correct is perhaps improbable. The diagram represents
the conclusions which the evidence we possess to-day appears to
warrant.

III. THe INTERPRETATION OF THE AURICULAR PRESSURE
CURVE AND THE JUGULAR PULSE TRACING

In passing to a consideration of the events involved in aes
production of the three main waves and three main depressions
of the tracings, it will first be convenient to examine the ultimate
factors to which each in its turn is due, whether it occurs on the
jugular, cesophageal, cardiographic, or auricular curve, and then
to briefly notice, where necessary, the modifications which occur
in the jugular tracing by the interposition of interfering factors.

(a) The First Positive or “a” Wave.—tThe presystolic
onset of this wave leaves little doubt that it is due to the con-
traction of the auricle, and it is universally attributed to this
cause. According to Fredericq ('°) it disappears from the
tracing, when as a result of tetanisation of the auricle, this
chamber ceases to beat. In ‘cases of partial heart block, in
which the auricles maintain a rhythm which is a multiple of the
before the left; that on the other hand the left ventricle contracts ‘03 to ‘04 sec.

before the right ; and that the delay between the onset of auricular and ventricular
systole is ‘08 to ‘10 sec. Schmidt-Nielsen’s figures (**) for the delay from right to

~ left auricle agree with those of Stassen. Compare Fredericq’s remarks (!).

1 Hering (”*) has confirmed this result by the use of vagal inhibition.

— oe

96 PULSE RECORDS IN THEIR RELATION TO

ventricular rhythm, the wave occurs more frequently upon the —
jugular tracing and at equal time intervals. Experimentally it
has also been shown that cessation of ventricular contraction does
not affect it. The wave is consequently established as due to
auricular contraction and auricular contraction only.

The question arises as to how it is propagated in the neck.
It may be supposed to result from regurgitation of blood into the
veins at the auricular systole. Such a view could apply only to
its production in the veins in the immediate neighbourhood of
the heart. But whether such regurgitation actually takes place is
by no means easy to settle. For even assuming that the right
auricle is supplied at the entrance of the swperior vena cava with a
specialised band of muscular tissue, the tenia terminalis (Keith),
which effectually closes the orifice by its guillotine action, yet it
might be supposed that a slight degree of regurgitation occurred
prior to the complete closure. The most direct evidence which ~
we possess is that given by Frangois-Franck, and this applies solely
to the veins of the neck. He found on fitting a Chauveau’s instru-
ment into these veins (in the donkey and horse) that there was
no sign of reflux, as indicated by a retrograde movement of the
blood column, at any period of the cardiac cycle.

Secondly, it may be attributed to a positive and centrifugal
wave of pressure originating in the auricle, or at the mouth of
the superior vena cava, and ascending the vein. Thirdly, the
wave may be regarded as due to the filling of the veins when the
outlet is obstructed ; namely, as consequent upon stasis. So far
as the second and third views are concerned there is little or no
evidence on which to base a discussion. The former tends to
recognise the wave as one mainly of pressure, the latter as one
mainly of volume. The curves obtained from the neck by means
of the tambour and pelotte are chiefly pressure curves, while the.
receiving capsule, usually used, yields curves for the most part

1 The instrument used was Chauveau’s hemodromograph. Both Frangois-
Franck and Chauveau and Faivre state that they have observed regurgitation from
the auricle into the roots of the great veins. But Francois-Franck says he is con-
vinced that there is no reflux into the neck veins by experiments too long to report.

The evidence for the tributaries of the inferior vena cava is even less complete,
There is of course every reason to suppose that it occurs in pathological conditions,
Experimental work on the subject is rendered very difficult, as the opening of the
chest which is usually necessary, produces serious alterations in the pressures of
the veins and right heart.

EVENTS OF THE HUMAN CARDIAC CYCLE 97

re ntative of volumes (Bard); it is possible that a careful
comparison of curves obtained by the two methods might throw
some light on the subject.

But whatever its method of propagation, the main fact rests
on an assured basis; the wave may be taken as an indication of
auricular contraction. ,

(b) The Second Positive or “c” Wave.—tThe discussion
which centres around this wave involves many questions of
considerable intricacy. :

It is sometimes held that no such wave occurs in the curve of
intra-auricular pressure, but the tracings of Porter and Fredericq
demonstrate it too clearly and constantly to allow of doubt.
While the weight of evidence is in favour of its presence, yet Frey
and Krehl fail to show its presence in their tracings, and recently
Hering (?**) has published a similar curve. Hering’s experiments
were performed under perfusion; the chest wall was removed ;
and the conditions generally were of an extremely artificial

character.”
In man its presence is attested not by the jugular curves so
- much as by the cesophageal, and the results of such observations
warrant the statement that it is a normal event of the human
intra-auricular pressure curve.

It is timed by all those who admit its occurrence as commencing,
in the auricle with ventricular.systole. According to Fredericq
the wave persists when by faradisation the auricle is caused to
fibrillate, and when the chest is opened. It disappears when the
ventricle ceases to beat. The wave must consequently have its
origin in ventricular systole.®

It is often held to originate in the bulging of the auriculo-
_ ventricular valves, at the onset of the systole (Chauveau, Fredericq,
and Porter). Chauveau in examining the heart of a living horse
(Chauveau and Faivre*) inserted his finger into the beating

1 Porter estimated the auricular pressure in the dog during auricular contraction
at9mm. Hg. This and other auricular pressures are given by Porter at page 533,
and will be subsequently. quoted. They are the pressures from one curve. .

® Moreover it must be stated that Hering (*) firmly believes in the presence
of this wave in the auricular pressure curve. He has recently commented upon
Song’ q his own curve and also that of Cushny and Grosh, published by
_% Similar experiments have been performed by Fredericq with the chest wall
act, either by vagal stimulation, or by stimulating through the chest wall.

' G

t

98 PULSE RECORDS IN THEIR RELATION TO

auricle, and reported that the ring is not completely closed in
ventricular systole, for the multiple dome of the tricuspid valves
is palpable at this phase.1 It must be remembered that such an
experiment is conducted with the thorax open, and also that
the palpating finger is frequently misled in attempting to gauge
changes of volume where there are also changes of pressure. Ina
consideration of the possibility of this bulging the experiments of
Roy and Adami are of importance. These observers recorded the
contractions of the papillary muscles by means of a hook passed
through the wall of the auricle and around a chorda; they
registered, simultaneously, the movements of the heart wall itself.
The conclusion arrived at was that there is an appreciable delay
between the onset of ventricular wall and papillary muscle con-
traction. Now this conclusion has been called in question by
Haycraft and Paterson. In the freshly excised heart they found

the contraction of the papillary muscles and adjoining part of the

ventricular wall to be synchronous. The subject has recently
received further attention from Saltzman (#4), who experimented
on the perfused heart. His findings, though they lack complete
uniformity, on the whole favour the view that the musculature
of the heart contracts according to the length of the branches of
the Purkinje system which supply the particular part considered.
The order of contraction in his typical experiments is as follows :
First, the base of the heart; secondly, the papillary muscles and
adjoining wall; and thirdly, the apex. Previous results, which
were conflicting, are thus brought nearer into line, thovgh they
do not show complete conformity.2 In four experimeuts the base
contracted on the average -031 sec. before the papillary muscles,
and the papillary muscles -036 sec. before the apex. There is a
variation on either side of these figures of ‘02 sec. Hering, how-
ever, in a preliminary note (**), states that he finds the papillary
muscles contract before either base or apex. Whatever the actual
events, the delayed pull of the papillary muscles and chorde
observed by Roy and Adami requires explanation, and it appears
rational to assume that it is due to delayed contraction, stretching
of the chords, or to a relatively greater shortening of the ven-
tricular muscle, and it constitutes evidence that under the con-
ditions of the experiment the valves bulge back into the auricle.

1 Fredericq (}*) makes the same statement.
2 In some cases Saltzman found the order of contraction reversed or irregular,

{s

THE EVENTS OF THE HUMAN CARDIAC CYCLE 99

At the moment when the valves may be supposed to balloon
into the auricle, that chamber is rapidly enlarging, and it may be
held that any decrease in the capacity of the auricles from the
former source will be fully compensated by the dilatation of the
organ. But granted that a positive wave of pressure is started
by the tricuspid valves,! its appearance in a recognisable form upon
the curve of intra-auricular pressure will depend on the relation-
ship of the pressures represented in this wave and the pressures
produced by other influences tending to expand the auricle; thus
there is no reason to deny the possibility of the appearance of the
wave on the auricular pressure curve. Again its conduction into
the veins of the neck will depend on the relationship of the rate
at which the wave is propagated and the rate at which the blood
enters the auricle, and, assuming its origin in the auricle, there
is every reason to believe that this relationship is such as fo allow
of conduction.
From the collected evidence we may conclude that the second
a positive wave is a real auricular event in man and that it may appear
tn the neck as a component part of the jugular pulse.
* In considering the causal factors of the “c” wave in the neck
z further complications arise. The shock of arterial pulsation may
5 be transmitted to the receiver, for it occurs at or about the instant
: when the “c” wave has its onset. There is also the possibility
of a direct conduction of the arterial pulsation, either aortic, in-
nominate, or carotid to the accompanying veins with which these
vessels are in contact. Each of these factors has been advocated
in turn as the chief element in the production of the “c” wave
(cp. Friedreich *, p. 289, Belski*). The leading points and
arguments alone require consideration.
It is held by Mackenzie, Gerhardt and Wenchebach that the
“ec” wave is due to the impact of the neighbouring artery ? alone.
Given in the main by Mackenzie, the chief evidence in favour of

* ‘1 The origin of the second positive wave in the bulging of the auriculo-ventricular
valves cannot be regarded as proven, though it appears to be the most rational view
to hold of its production. Hering has convinced himself that it is independent of

__ the shock of the root of the aorta, and auricular branches of the same, by numerous

experimental researches, but he does not detail the evidence (**).

? While the actual statement is frequently made that the impact is from the
carotid, yet it is understood that an arterial impact is intended, and that the
?p r artery involved is that which lies in the neighbourhood of the receiver
means of which the tracing is obtained. -In the light of Keith’s anatomia
cription it would appear that the artery is usually the subclavian.

100 PULSE RECORDS IN THEIR RELATION TO

this view is as follows: The proof of the occurrence of the second
positive wave in the auricle is not considered as final’; tracings
of an obviously arterial nature are obtained with the greatest
ease from many points of the neck; as the receiver is moved
higher in the neck the tracing gradually acquires the arterial
character and eventually loses all trace of jugular waves; the
wave is said to be synchronous with the primary wave of the
carotid pulse ; it is occasionally absent from the jugular tracing
when the latter has a large amplitude ;? it is said to be absent
from a type of liver pulse known as the auricular liver pulse.

There are many observations in opposition to this evidence.
Morrow (°"») finds that clamping the carotid ‘near its origin does
not affect the wave.’ Fredericq ('*°) states that in animals the
wave persists when the artery is completely separated from the
vein from which the record is taken. Bard (1°) has also noted the
““c¢”? wave in a subclavicular vein, isolated from all arteries, and
Rautenberg has recorded it in its full dimensions in the superior
vena cava of a dog. Hering states that in heart bigeminus where
the second pulse beat has a longer presphygmic interval than the
first, there is no corresponding delay in the appearance of the
““¢” wave in the neck.

There can be no doubt that in many tracings of the jugular
pulse the arterial shock contributes to the “c” wave; the diffi-
culty is frequently in avoiding the arterial pulsation. The main
question is as to whether it is the only factor, or as to whether
on occasion it may contribute but slightly or even take no part
in its production. The character of the wave is of importance.
In many tracings it is very prominent and peaked, and shows

1 This question has already been dealt with as fully as space will permit.
It is questioned if the apparatus used in recording auricular pressures may not tend
to the production of the wave. The apparatus has varied very greatly, as has
also its position in the process of recording ; yet the majority of the curves show
the same characters. Porter has registered the wave in the pulmonary veins, and
Rautenberg in the superior vena cava ; more recently Delchef has recorded the wave
in the inferior vena cava (Archiv. Internat. d. Physiol., vii. 1908, p. 96).

2 Hering (*) explains this by the magnitude of the “a” wave in the tracings
given, and states that the “ carotid shock” may also disappear.

3 Morrow holds that the essential part of the ‘“‘c” wave is conducted from the
auricle where it may be produced by—

1. A force exerted during ventricular systole, through the auriculo-ventricular
valves. i

2. Contraction of the ring of muscle in the auriculo-ventricular junction.

3. Pressure exerted upon the auricles by the systolic twist of the heart.

_ THE EVENTS OF THE HUMAN CARDIAC CYCLE 101

no outward resemblance to the waves of the pure carotid pulse.
Briefly, in such cases it must be assumed that the primary wave
is alone transmitted, an assumption which it is difficult to make.
It may be asked why, if the primary wave is recorded, the
dicrotic should not also leave its impression on the tracing. Again,
it requires as a rule a firmer pressure to bring out a maximum
arterial tracing than it requires for the venous. Venous tracings
of the greatest amplitude are often to be obtained by the lightest
application compatible with closure of the mouth of the receiver.
We have further seen that the synchronicity of the “c” wave
and the carotid shock has not been fully established (Bard and
Bachmann). The tracings given to show simultaneous onset often

_ show a slight deviation, which may of course be explained by a

difference in level at which they were obtained and to a slight
transmission delay. The argument that the “c” wave is absent
from the liver pulse is the strongest of those sibicht in favour
of its arterial origin, and has not yet met with a satisfactory
explanation. The liver tracings are of a very complex nature,
combining expansile pulsation with up and down movements of
the whole organ. Rautenberg (**°) has given a tracing in which
the ““c” wave appears to be present, but it is possible that in
this instance insufficient care was employed to avoid the trans-
paved shock from the aorta. The author is of opinion that the
*“¢” wave is occasionally visible in the veins of the neck.

Finally, it cannot be affirmed at present that the “c” wave is
purely arterial or purely venous in origin, and while : cannot be
denied that both factors may be contributory under certain conditions,
it is highly probable that in one case the arterial and in another the
venous element will predominate.

As to whether there is a transmitted shock from the aorta or its
branches direct to the veins, there is little evidence beyond that
already examined. Fredericq points out that, as the rate of trans-
mission is dissimilar in artery and vein, the view is incompatible
with the opinion that the waves appear together in the neck.
Morrow uses, as an argument against such transmission, the fact
that the “c” wave is frequently absent from the femoral venous
curve, though the venous channel which connects the femoral vein
to the heart is throughout in close contact with pulsating arteries.

~ 2 The question has been recently discussed. more fully by the author (Brit. Med.
Journ., Nov. 1905).

102 PULSE RECORDS IN THEIR RELATION TO

Whatever the ultimate factors involved, the practical outcome
remains unaffected. The “c” wave in the jugular may be safely
taken for clinical purposes as synchronous with the primary wave of
the arterial pulse in the neck at the same point, and it thus forms a
valuable standard in the interpretation of tracings.

(c) The Third Positive or “v” Wave.—The chief difficulty

ce ”

in interpreting the third positive or “v” wave lies in the dif-
ference of opinion in regard to its instant of onset. The ex-
planation of its occurrence, as given by any particular author,
depends upon the time relations which he accepts for its various
phases. Thus, those who believe in its onset during systole
of the ventricle, consider that the venous flow which fills the
auricle during this phase is an important contributory cause
(Potain, Porter, Gottwalt, Mackenzie, Morrow, Hering). Those
who regard it as arising with the commencement of ventricular
diastole, attribute it to an elevation of the auriculo-ventricular
ring (Porter,? Gerhardt). A similar view is held by Wenchebach.
It has also been attributed in part to dicrotic rebound at aorta
and pulmonary orifices (Riegel *) ; and to tricuspid regurgitation *
(Mackenzie).

For our present purposes it will be convenient to regard the

onset of the ““v” wave as inconstant in position, and to briefly

discuss those factors held to take part in the production of the
wave, either in that portion of it which is said to occur before,

1 The second positive wave was estimated by Porter as representing an auricular
pressure of 5 mm. Hg.

2 Porter recognised it as a contributory cause.

3 Cp. criticisms of Gerhardt and remarks by Hering (**).-

4 The difficulties of this question are very great. That the wave is enhanced
when there are evidences of tricuspid regurgitation is generally admitted. The
opinion rests chiefly on the proposition that tricuspid reflux may be a normal
event. Such a reflux is not admitted by physiologists, but is strongly held
by the northern schools of clinical medicine. The evidence cited is the
presence of a systolic murmur, regarded as an indication of tricuspid insufficiency.
Whether those presenting such a murmur, a sound which is said to be of common
occurrence, are to be recognised as falling within the category of normal subjects,
is a question outside the bounds of this article. Full references and many inter-
esting observations may be found in the writings of Gibson (!") and in the first
articles of Mackenzie. Our ignorance of the conditions under which tricuspid
leakage may occur in its earlier stages appears to be very great, and little or no
experimental work has been done on the subject. Statements attributing to
Gibson the view that regurgitation is a factor in the production of the ‘‘v” wave
are without foundation.

THE EVENTS OF THE HUMAN CARDIAC CYCLE 103

or in that which it is claimed occurs subsequent to the S.C.
closure. .

During the systole of the ventricle, the auricular pressure falls

and the blood pours into that chamber. There is no exit for the

stream and the reservoir must gradually fill. If the systolic
plateau is prolonged or the filling is rapid, it is reasonable to expect
that the pressure in the auricle will rise, for any influences, other
than the passive one, which tend to dilate the auricle, must of
necessity be diminishing during the last phases of ventricular
systole. When in a venous or auricular curve, there is a rise
which can but be attributed to events occurring before the ter-
mination of systole, it is rational to attribute it to this auricular
filling and to a stasis wave passing back into the veins. As yet
no curves indicative of the changing velocities in the large veins
have been obtained.

The second possible factor in the production of the “v”
wave, namely, the upward spring of the auriculo-ventricular
junction at the beginning of diastole, must be dealt with at greater

length.

: The direction of movement of the different parts of the heart
7 wall has been for many years the subject of contention, and there
is accumulated evidence that the earlier observations, in which the
heart was exposed, were fallacious. The experiments which chiefly
concern us are those of Briicke (°) and Haycraft (74). The method °
employed was the same in each case, and is in all probability a
: very accurate one. Needles were used, and the chest wall and
heart muscle was transfixed. The needles carried light straw
levers from the movements of which the excursion of the heart
___-wall could be observed. As a result it was shown that in systole
the apex is the only fixed point of the musculature, and that all
other parts tend to move towards the mid-line and apex. The
auriculo-ventricular line is considered by most authorities to have
a decided downward movement in systole, and a corresponding
upward fling in diastole. Keith, who regards the mouths of the
great vessels as other fixed points, has recently laid much stress -
on this movement of the A-V line. According to this author,
whose researches are in the main anatomical, the systole of the
ventricle causes expansion of the auricle, and diastole of the ven-
_ tricle its collapse. The auricle is opened like a concertina, and
_ the upward movement of the A-V line in diastole is said to pro-

104 PULSE RECORDS IN THEIR RELATION TO

pagate a positive wave in the uppermost chamber.! Now the
movements of the A-V line are also offered as an explanation of
an earlier negative wave (second negative or “‘ x’” depression), and
the view, as we shall subsequently see, has much to support it.
If the descent of the A-V line is sufficient to produce a negative
wave, its ascent must assuredly be adequate to determine a second
wave of equal intensity but of opposite sign. The explanation is
a feasible one, and there remains but one serious difficulty. A
positive wave of the sort, if propagated, may be entirely swamped
by other events occurring at or about the same time. And the
event which has to be considered is the effect of the lowering of
ventricular upon auricular pressure. It must be noted that the
factor can only be of avail between the S.C. and A.O. points; and
until there is more unanimity as to the timing of these events

opinion must necessarily vary as to the part played by the A-V line |

in the production of the “v”’ wave.?

The interpretation of the “v”’ wave which has just been dis-
cussed attributes it to a movement of the ventricle, and makes it
independent of auricular contraction or relaxation. Fredericq has
found that when the ventricle is thrown into a state of fibrillation,
the wave is abolished. Frangois-Franck and Morrow, on the other
hand, give curves in which some portion of it at least remains when
the ventricle is no longer beating. It is for this reason that Morrow
is more inclined to attribute it to inflow and stasis. In cases of
heart block there is as a rule no “v” wave corresponding to the
purely auricular beats, but in a tracing of Wenckebach’s a small
wave is seen. It ts probable that both factors play a part in the
production of the wave under certain circumstances ; that with quick
filling of the auricle or sustained plateau the first will be prominent,
and that with slower filling and quicker heart beat the pressure in the
auricle will be low when the ventricle passes into diastole, and that
as a consequence the tricuspid valves will open later. Under these
circumstances the second factor may be the more pronounced.

1 This movement of the auriculo-ventricular junction was described by Chauveau
in 1887 (Assoc. frang. p. l’avanc, d. Sc.), in a paper in which he gives a figure (No.
12), illustrating views very similar to those recently published by Keith. The
movement is fully discussed by Fredericq (!*), and many other writers,

2 Allowing the S.C. to A.O. instant at ‘04 to ‘06 sec., there is time for the
production of an appreciable wave. But this time interval is very difficult to
measure with any degree of accuracy, and it cannot be held that our estimates of
it are at present anything more than approximate.

vv

‘THE EVENTS OF THE HUMAN CARDIAC CYCLE 105

If the view is accepted that both are contributory causes, not
only do many of the apparently discordant observations assume
an aspect of greater harmony, but the occasional division of the
wave at or about the time of S.C. closure is no longer difficult to
appreciate.’

(d) The First and Second Negative Waves, or “x” and
“x’” Depressions.—The two first depressions of auricular and
jugular tracings may be considered together, for the line of
descent is usually continuous, and is but broken by the second
positive or “c” wave. The complete depression commences
with the relaxation of the auricle,? and is continued well into
the systolic plateau. The fall in pressure is a marked one, and
attracted much attention from earlier writers, for it causes a
collapse of the veins of the neck. Hunter (*°) regarded systole
of the ventricle as a valuable aid to the filling of the auricle, by
the creation of a partial vacuum in the chest. This view was
readvanced by Briicke and Mosso. Francois-Franck performed
some experiments with a schematic apparatus to demonstrate its
ft possibility. But Francois-Franck himself, and also Gottwalt and
. Riegel, clearly showed that it is a factor of little importance, for
the fall remains after the chest is opened. Nevertheless it cannot
be denied that it contributes, for the systole of the ventricle pro-
duces a fall of intra-pleural pressure, which may be recorded by a
manometer in connection with that cavity. It is certain that it
is not the main cause of the fall.

Active relaxation of the auricle has never been demonstrated,
and its enlargement in the normal chest is attributable at its
onset to the low pressure in the chamber surrounding it (Frangois-
Franck). But the auricular relaxation is in itself insufficient to
account for the complete fall,* though it suffices to explain that
portion of it which occurs before the commencement of ventricular

| a eg

1 Bard finds this notch so constantly that he considers, and perhaps with justi-

fication, that the origin of the separate’ portions of the wave should be separately
_ discussed. It must be noted that Hering and Rautenberg strenuously deny. the
intervention of the second factor.

Porter gives the third positive wave a pressure value of 5 mm. Hg.

* Porter found that it occurred, as a rule, a little before relaxation of the
auricular appendix. This writer estimates the value of the complete fall at —10
mm. Hg.

* Fredericq’s tracings, with intact chest wall, in which auricle and ventricle
dissociated.

106 PULSE RECORDS IN THEIR RELATION TO

systole (first negative wave or “x” depression). Porter states that
relaxation of the auricular appendix proceeds for a variable time,
terminating at the beginning or end of the second positive wave ;
but the observation is of little value, for under the conditions of his
experiment the relaxation would depend in the main on passive
filling. When the ventricle is inhibited by vagal inhibition in the
dog, or if clamped off from the auricle in the tortoise, a negative
wave is still present (Francois-Franck); it also occurs in the
jugular pulse in certain cases of heart block when the ventricle
fails to respond to the auricular contraction (Wenckebach).
Morrow’s tracing (Fig. 12) shows similar characteristics ; but while
the ventricle is inactive, the depression, though still present, is
reduced in size. While Francois -Franck found it abolished by irri-
tation of the auricle, Fredericq ('*°) has shown that this is not
the case, and states (”*) that when the auricles have passed into .
delirium, at each ventricular contraction the auricular appendices
diminish in volume, and are, as it were, aspirated towards the cavity
of the auricle, and the negative wave persists.1

From these observations it is clear that the systole of the
ventricle plays a considerable part in causing the depression, and
it has been attributed by many writers to an event occurring at
this time, namely, descent of the A-V line (Fredericq, Porter,
Wenckebach, &c.).

In concluding this section it may be said that the two negative
waves which together form the most prominent depression of the

1 Frangois-Franck’s observations were carried out with the chest open. Fredericq
has controlled his own observations by repeating the experiments with the chest
intact, the advantages of which are obvious.

There is a fact which is often insufficiently appreciated, namely, that the
circulation is completely obstructed at two points during approximately half the
cardiac cycle. The obstructions are situated at the auriculo-ventricular valves,
Nevertheless it is only during a small fraction of the cardiac cycle, during systole
of the auricles, that blood is not pouring into the heart. The main function of the
auricles is not to load the ventricles ; the ventricles fill well when the auricles are
paralysed, and by comparison the auricles are small chambers. They serve mainly
as reservoirs, and during their brief contraction the large veins in their vicinity
adopt this function. In contracting the auricles return to the state of potential
reservoirs,

So the over-engorgement of the veins, which would otherwise occur, is prevented ;
and so it happens that in spite of the fact that the circulation of man is never an
open path, the flow of blood through peripheral vessels is constant and uninter-
mitting. While in heart block yenous stagnation is rare, clinical observations of
to-day point to its frequent origin in inefficient, ill-timed, or obstructed systole of
the upper chambers.

EVENTS OF THE HUMAN CARDIAC CYCLE 107

auricular and venous curves are due to three causes; the increased
negative pressure in the chest, consequent on ventricular systole ; the
auricular relaxation dependent on the original intra-pleural pressure ;
and the stretching of the auricular walls as a result of ventricular
systole. Of these causes, the first is insignificant; the second is
most active during the early phases, and the third most prominent
in the later phases of the depression.

(e) The Third Negative or “y” Depression.—With the
diastole of the ventricle, the pressure within it falls rapidly
and may become markedly negative. The fall of pressure is
accompanied by the opening of the auriculo-ventricular valves,
and the blood contained in the auricle passes into the ventricle.
As a consequence, the pressure in the auricle falls, and the depres-
sion in the auricular tracing timed to occur with the opening of
the valves } is universally attributed to this cause. The depression
may be due not only to a relief of the previous stasis, but to a
_ transmitted pressure wave of negative sign. To what extent the
negative pressure is thus transmitted to the auricle is uncertain.
Porter estimated the auricular pressure corresponding to this event
at ‘+5 mm. Hg, and as a consequence concluded that the negative
pressure in the ventricle has little direct effect upon the pressure
in the auricle. Porter’s experiments were carried out on dogs and

1 The timing of this instant in man and the dangers which the methods involve
have been repeatedly referred to; to emphasise them now entails tiresome but
necessary reiteration. The interpretation of the ‘‘y” depression may be correct,
but it has not been arrived at by scrupulously accurate methods. It cannot be
said that the intra-auricular curve falls at the A.O. instant, while the curves of
Porter and those of Young and Hewlett and Rautenberg show it otherwise.
Moreover the drop in the jugular curve must be placed later, to allow for the
delay in transmission which undoubtedly occurs. So that if the drop in the
jugular curve is to be placed at the A.O. instant, the drop in the human intra-

_ auricular curve must be placed approximately 1 sec. earlier, at a point at or near
the closure of the semilunar valves.

Almost all writers, early and late, express the opinion that the drop occurs both
on auricular and jugular curves at the A.O. instant, or refer to unanimous state-
ments to that effect. And it is attributed by similar processes of reasoning to a
definite cause: In the above synoptic account the same line is taken, but for that
very reason this proviso is essential. For if the auriculo-ventricular valves are
bulged into the auricle during early systole, they must remain bulged during the
plateau, and when the ventricular pressure begins to fall the tension in the valves
soaeeeg decrease, The fall in auricular pressure should therefore commence slightly

than the A.O. point, namely, at or near the S.C. point. Porter, who took
“ifferential curves of the pressures in the two caritios, actually found that the fall
: auricular pressure commenced at this instant. —

108 PULSE RECORDS IN THEIR RELATION TO

the chest was open. In this connection it must be remembered
that although lower pressures have been recorded in the ventricle
with the chest wall uninjured, yet pressures as low as —28 and
— 38 mm. Hg have been found in dogs by Goltz and Gaule, de Jager
and others,! with the thorax open.

The jugular and cesophageal curves in man often show the third
negative wave or “y” depression to be of considerable extent,
and a relief of stasis is certainly insufficient to account for it.

3
¥
$
Ys
bd

Fic. 3.

The evidence of the jugular pulse in this respect is occasionally
such as to indicate that the inflow from the veins is as great
during ventricular diastole as during ventricular systole. It is
probable that the larger the ventricle the greater is its power as
a suction pump.

APPENDED NOTE

In sending off the proofs, the author is able to include a simul-
taneous jugular curve and electrocardiogram (Fig. 3): The figure
shows :—time in % sec.; the jugular curve, taken photographically

1 Full references to these obsexvations will be found in Porter’s article.

with the polygraph, in which a delicate lever replaced the usual
pen, which is heavy for the purpose; and an electrocardiogram
taken in Professor Waller’s laboratory with an Einthoven “ string
_ galvanometer.” The jugular curve has been marked with the
_ letters used by Mackenzie and employed in the text. The
_electrocardiogram has been marked with the letters used by
Kinthoven ; P represents auricular contraction, R and T are the
result of ventricular contraction. The curves were obtained from
a lad with a prominent jugular pulse. :

The a-c interval, as measured in the jugular tracing, in the
first and last curves is ‘14 and ‘12 sec. respectively. The time
interval between auricular and ventricular contraction, as measured
in the electrocardiogram, is ‘11, -12, and ‘12 respectively. It will
_ be seen that the delay in the appearance of “a” and ‘‘c” waves
in the neck is practically identical, namely -12 sec., and that the
a-c interval is, as taken by this method, less than } sec. The
delay of -12 sec. in the appearance of the waves in the neck is the
uncorrected value. A deduction of ‘04 sec. must be made for
instrumental delay in the jugular curve. The true value is
consequently -08 sec.

The figures given are in agreement with others obtained from
the same subject, and accord very closely with the estimated
values quoted in the text.

‘

BIBLIOGRAPHY

1 Bard, (a) Jour. d. physiol. e. d. pathol. gén., mai 1906, pp. 454-459.
(b) Ibid., pp. 466-479. (c) Archiv, d, Maladies du Coeur, &c., juin 1908,
No. 6.
* Baum, Verhandl. d. phys.-med. Gesell. z. Wiirzburg, N. F., Bd. 38,
1906, s. 61-102.
* Bayliss and Starling, Internat. Monatssch. f. Anat. U. Phys., Bd. 11,
Hit. 9, 1894, pp. 426-435.
* Belski, Zeitsch. f, klin. Med., Bd. 57, Hft. 5 u. 6, 1905, s. 565,
5 Briicke, Vorlesungen iiber Physiologie, Wien, 1885, Bd. 1, Aufl. 4, s.
178-179.
* Chauveau and Faivre, Gaz. méd. de Paris, T. xi,, 1856, p. 406. :
? Chauveau aud Marey, ibid., 1861, p. 675.
§ Edgren, Skand. Archiv. f, Physiol., Bd. 1, 1889, s. 67-151.
__ * Einthoven and Geluk, Archiv. f. d. ges. Physiol., Bd. 57, 1894, s,
617-639,
® Erlanger, Johns Hopkins Bulletin, No. 177, vol. 16, 1905, pp, 394-397.

ce _

110 PULSE RECORDS IN THEIR RELATION TO

1 Frangois-Franck, Gaz, hebdo. d. méd, e. d. chir., fév., mars, av. 1882,
pp. 92, 225, and 255.

12 Fredericq, (a) Archiv. d. Biol. (Paris), T. 8, 1888, pp. 497-622. (b) Archiv.
Internat. Physiol., iv. 1906-7, pp. 57-75. (c) Ibid., v. 1907, pp. 1-25.

8 Frey and Krehl, Archiv. f. Anat. u. Phys., 1890, s, 31-88.

4 Friedreich, Deutsch, Archiv. f. klin, Med., Bd. 1, 1866, s. 241-291,

% Galabin, Journ, Anat. and Physiol., vol. 10, 1876, pp. 297-319,

16 Gerhardt, Archiv, f. exper. Path. u. Pharmak., Bd. 34, 1894, s. 402-445,
and Bd. 47, 1902, s. 250-266.

1 Gibson, Edinb. Med. Journ., 1880, vol. 25, pp. 979-991.

18 Gibson and Ritchie, Practitioner, vol. 78, No. 5, 1907, p. 602.

1 Gottwalt, Archiv. f. d. ges. Physiol., Bd. 25, 1881, s. 1-30.

2% Griinmach, Archiv. f. path. Anat., Bd. 102, 1885, s. 569-577.

* Haycraft, Journ. of Physiol., vol. 12, 1891, pp. 452 and 473.

2 Haycraft and Paterson, Journ. of Physiol., vol. 19, 1896, p. 262.

3 Hering, (a) Archiv. f. d. ges. Physiol., Bd. 106, 1904, s. 1-16. (b)
Verhandl. d. Kongress f. in. Med., 23. Kongress, Miinchen, 1906, s. 138.
(c) Deutsch. med. Woch., 1907, No. 46. (d) Zentralb. f. Physiol., Bd. 21, |
No. 22.

*4 Hewlett, Journ. Med. Research, O.S8., vol. 17, 1907-8, pp. 119-136.

% Hunter, A Treatise on the Blood, Inflammation, &c., London, 1794,
pp. 185 and 187.

6 Hiirthle, (a) Archiv. f. d. ges. Physiol., Bd. 49, 1891, s. 29-104. (b) Ibid.,
Bd. 60, 1895, s. 263-290. (c) Ibid., Bd. 43, 1888, s. 399-437.

27 Joachim, Berl. klin. Woch., Feb. 1907, s. 215-216.

* Keith, Journ. of Anat. and Physiol., vol. 42, Oct. 1907, pp. 1-25.

* Keyt, Sphygmography and Cardiography, London, 1887.

3 Lancisi, De motu cordis et aneurysmatibus, 1740 (earlier ed., Romae,
1728, is cited by Baum, loc. czt.).

31 Tandois, Die Lehre vom Arterienpuls, Berlin, 1872, s. 307.

8 Mackenzie, (a) Journ. of Path. and Bact., O.S., vol. 1, 1893, p. 53 ; ibid.,
vol. 2, 1894, pp. 84-154. (b) The Study of the Pulse, &., London, 1902.
(c) Amer, Journ. Med. Scien., July 1907, pp. 1-23. (d) Diseases of the Heart,
London, 1908.

33 Marey, (a) Physiologie médicale de la circulation du Sang, Paris, 1863.
()) La circulation du Sang, &c., Paris, 1881.

34 Martius, Zeitsch. f. klin. Med., Bd. 13, 1888, s. 344 and 346.

3 Minkowski, Zeitsch. f. klin. Med., Bd. 62, 1907, s. 371-384 ; and Deutsch,
med. Woch., 1906, No. 31, s. 1248-1250,

% Morgagnt, De selibus et caus. morbor., Napoli, 1762 (cited by Baum,
loe. ctt.).

8? Morrow, (a) Archiv. f. d. ges. Physiol., Bd. 79, 1900, s, 442-449. (b)
B.M.J., Dec. 22, 1906, p. 1807.

38 Mosso, Die Diagnostik des Pulses, u.s.w., Leipzig, 1879, s. 60-63.

3° Porter, Journ, of Physiol., vol. 13, 1892, pp. 513-553.

© Potain, Mém. d. 1. soc. méd. d. h. d. Paris, mai 1867, pp. 3-27.

‘1 Riegel, Deutsch. Arciiiv. f. klin, Med., Bd. 31, 1882, s. 1-62.

42 Rautenberg, (a) Deutsch. Archiv. f. klin, Med., Bd. 91, 1907, s, 251-290.

\
\

\ °

i . |
. « _

ad —— hare
‘HE EVENTS OF THE HUMAN CARDIAC CYCLE 111
Sy joen: Klin, Woch., iv. 1907, No. 21, s. 657. (c) Zeitsch. f. klin, Med., Bd.
r 35, Sept. 18, 1908. (d) Berl. klin, Woch., iv. 1907, No, 46, s. 1478,
* Roy and Adami, Practitioner, Bd. 44, 1890,
“ Saltzman, Skand. Archiv, f. Physiol., Bd. 20, 1908, s. 232-248,
*® Schmidt-Nielsen, Archiv. Internat. Physiol., iv. 1906-7, pp. 417-433.
* Stassen, ibid., v. 1907, pp. 60-75.
” Tigerstedt, Skand. Archiv. f. Physiol., Bd. 20, 1908, s, 249.

“ Weldemeyer, Untersuch, ii. d. Kreislauf. d. Blutes, Hannover, 1828
(cited by Baum, loc. cit.).

_ ® Wenckebach, Archiv. f. Anat. ii. Physiol. (Physiol. Abth.), 1906, s.
~=—- 297-354.
+5 og Young and Hewlett, Journ. Med. Research, O.S., vol. 16, 1907, p. 497-

THE VASCULAR SYSTEM AND BLOOD
PRESSURE

By LEONARD HILL

EXPERIMENTAL OPERATIONS ON THE VASCULAR SYSTEM

CARREL has opened up a new field of experimental work by show-
ing that it is possible to join together the divided ends of arteries
or veins, or a vein with an artery. Having inserted thread
through each end of the divided vessel, at three points in the
circumference apart from one another, he brings the ends of the
vessel together by these threads and stitches intima to intima
with a very fine needle and a running thread.1_ The outer coats
are finally stitched together. Then the blood flow being re-
established, he watches for the slightest sign of oozing, and if
any, stops it by further stitches.

He has succeeded not only in stitching an artery to a vein,
but in inserting a length of transplanted artery or vein between
the ends of a divided artery. More wonderful than all, he has
succeeded in transplanting whole organs from one animal to another.
In one experiment he dissected a length of the carotid of a young
dog, kept it in physiological salt solution for twenty days at 32° F.,
and finally inserted the piece in the course of the abdominal aorta
of a cat. On the forty-eighth day after he opened the abdomen
and found the artery of normal appearance and serving its func-
tion well. On the seventy-seventh day the cat was in perfect
condition.*

‘“‘Seven months ago,” he writes, “one of the animals had the

1 The needles are sixteen cambrics, the threads single strands of Chinese twist
silk sterilised in paraffin oil.

2 John Hunter stated that the arteries have considerable surviving power. On

transplanting them he obtained union thirty-six hours after their removal from the
body. Palmer's Edit., vol. iii. p. 157.

3 Guthrie not only has repeated this experiment, but has inserted a length of

artery hardened in formol; at the end of twenty-two days it was serving its
function perfectly. The dead artery is the scaffold on which repair of the living
vessel takes place. (Journ. Amer. Med. Amie 1908, 1. p. 1035.)

1 .

THE VASCULAR SYSTEM 113

peripheral end of the external jugular vein united to the central
end of the carotid artery. Now the circulation through the vein
is apparently as active as it was on the day of the operation. In
another case, where the jugular has numerous collaterals, there
appears to be some dilatation of the main portion of the vessel,
and feeble pulsations can be detected in the jugular of the other
side. In three cases of reversal of the circulation through the
thyroid gland the results seem to be permanent, even after

Fic. 1.—External jugular united to Fic. 2.—Preparation of host for receipt
carotid artery. Reversal of circulation of kidney graft. The viscera are covered
through the thyroid gland. A method with pads wet with warm saline during
of modifying the function of the gland the operation. Clips on divided aorta of
by producing hyperemia. vena cava.

several months. On no dog kept in the laboratory has oblitera-
tion of the vessels occurred, even after several months.

* At the present time we can only state that seven months after
the operation the veins have performed the main arterial functions
and that occlusion has not occurred.”

Carrel and Guthrie amputated and replanted a dog’s thigh.
“The circulation was easily and entirely re-established. The
pulsations of the femoral, popliteal, and posterior tibial arteries
were as strong as the pulsations of the corresponding arteries of
the other side. The arterial circulation was seemingly normal.
The capillary circulation was exaggerated, the temperature of the

H

114 THE VASCULAR SYSTEM

limb being higher and its hue redder, owing doubtless to the fact
that the vaso-motor nerves were cut. The venous circulation
was observed to be good immediately after the operation.” The
collodion dressing, however, contracted and impeded the circula-
tion in the limb which became swollen, so that after fifty hours
the animal was killed.1_ The most striking of these remarkable
experiments is that of transplanting the kidneys from one cat
to another. Secretion of urine may begin immediately after the
arterial circulation is re-established. In the best cases the func-

FS. Leh ae7/.

Fic. 3.—The graft aay for insertion. Fig. 4.—The operation completed.

tion of the kidney was for some twenty days almost normal.
120 to 160 c.c. of urine a day were secreted, and urea in proportion
to the proteid eaten. When fedl on raw meat 2°7 to 5:1 grms. of
urea were passed per diem. The\cats were fat and in good health,
with glossy skin and good appetites, playing, running, and jumping
about the room. Nevertheless there was some albumen in the
urine, and cedema of the kidneys leading to their slow and pro-
gressive enlargement. Upon the twenty-ninth day one cat was
well, and then gastro-intestinal symptoms set in and the animal
died on the thirty-first day.

1 Guthrie reports “a transplanted fore-limb without any serious derangement of
metabolism, six days after the operation.” (Journ. Amer. Med. Assoc.,1908, li. p.1658.)

AND BLOOD PRESSURE 115

In one case the kidneys of a middle-aged cat were successfully
grafted on to a young adult. The animal lived as a normal cat
for fifteen days, but then became emaciated and died on the thirty-
sixth day. The arteries of the young cat, the costal and bronchial
cartilages and all the scar tissue where it had been incised were
calcified as hard as glass. The transplanted kidneys and renal
vessels, on the other hand, showed no sign of calcification. The,
kidneys were somewhat cedematous but showed no very serious
pathological change. This result—the calcification of the host

Fic. 5.—The cat three weeks after the operation.

but not of the graft—was only obtained once, but it is one which
opens up a wide vista of new ideas and research.

In carrying out the operations the kidneys are deprived of
circulation for more than an hour, and are washed out with
Ringer’s solution. The vaso-motor nerves are cut—it has been
proved that kidneys can functionate normally after this operation—
and the anemia probably destroys the local renal ganglia, for
nerve cells in the central nervous system do not recover function
after at most twenty minutes! total deprivation of blood flow... It
is very important in such operations that the veins be given their
normal situation and direction. The writer’s explanation of this
is that every departure from the normal course by preventing the

1 In one case twenty-nine minutes (Guthrie).

116 THE VASCULAR SYSTEM

full action of the respiratory movements on the renal circulation
leads to diminished flow and cedema of the transplanted organ.
The capillaries and veins are naturally so arranged to run that
each muscular action of the body promotes the flow in them to-
wards the heart. It is important also that no bleeding take
place into the connective tissues during or after the operation, as
blood has an irritative effect and produces sclerosis. Bier has
utilised this property, and injected blood to excite callous forma-
tion in cases of pseudo-arthrosis.

The experiments of Carrel bring just within the limits of the

Fig. 6.—Operation method of J. E. Sweet (Journ. Hap. Med. vii. 163, 1905) for
joining the portal vein and vena cava (Eck’s operation). The double thread is the
wire of an electric cautery, and cuts the opening between the two vessels.

possible the operation of transplanting from a man killed by an
accident such an organ as the thyroid into the neck or other part,
where it may carry on its function and compensate for thyroid

inadequacy in the recipient. Guthrie has succeeded in exchang- |

‘ing the ovaries of black and white Leghorn hens, and finds the
foster-mother modifies the colour of the chicks hatched from the
eggs laid afterwards. The controls gave pure white or black
chicks.

THe ELASTICITY AND CONTRACTILITY OF ARTERIES

When the carotid artery of the ox or horse is exposed immedi-
ately after death, it is found to be soft and flaccid, more or less
flattened in section, with a large bore usually 5 or 6 mm. in diameter.
On exposure to the air, cooling, and especially on manipulation

AND BLOOD PRESSURE 117
the artery quickly becomes rigid and contracted, and circular in
section, with a calibre greatly lessened, the diameter being re-
duced to 2 or 3mm. orless. The artery becomes often so stiff that
a piece 7 or 8 mm. long may be held by one end in an almost
horizontal position. Arteries left undisturbed in situ for a day or
two after death and then exposed may show little sign of contrac-

Ba

a »

nth
il

Vchichs

Se

LM

os
—_

‘se — yi oe

ITS

——
———— —
—

{

3 W3
i
i

Gi

A

/2chicks

Fic. 7.—B2, white o ry grafted on black ; fertilisation by white cock. Ws, black
ovary grafted on white ; fertilisation by black cock (Guthrie).

tion at first, but under the influence of manipulation may soon
contract strongly and persistently, the contracted state lasting for
q days. John Hunter noticed that the arteries of the umbilical cord —
contracted up to the third day, and not on the fourth. Freezing
relaxes permanently the arteries, so that if the “pluck” of a
freshly killed ox be bought, and one piece of carotid be taken and
frozen on a freezing microtome, and another be manipulated, a
ing contrast between the two becomes demonstrable.

118 THE VASCULAR SYSTEM

Heating to 50° C. also causes a permanent loss of contractility.
The carotid behaves to moderate changes of temperature like
other unstriped muscle—retractor penis of dog, iris and bladder

—h

Fic. 8.—-Carotid (ox), contracted. Transverse strip; 8 hours p.m.
Second loading after 1? hours.

strips of cat, strips of lower portion of gullet—contracting on
cooling and relaxing on warming. The relaxing effect of warmth
is taken advantage of by the surgeon in passing catheters, &c.

The aorta and pulmonary artery con-
tract much less than the carotid, for in
them there is less muscle and more elastic
tissue.

In the case of a relaxed artery
MacWilliam —to whom we owe these
observations—finds the greatest amount
of extension is produced by the first

Fic. 9.—Elongation of con- +s . . +s
tracted artery with rise of #ddition of weight. Successive additions

internal pressure, 0-300 mm. cause diminishing increments in length

Hg. Length 16 mm. Ss went :
z ct per unit increase of weight. In the

early part of the process of stretching a contracted artery, the
resistance is solely muscular; later, when the muscular resistance

AND BLOOD PRESSURE 119

has been so far overcome that the strip is stretched to what would
be the normal length of a passive or relaxed artery, further stretch-
ing brings into play the resistance of the elastic elements and the
extension curve then becomes like that of a
relaxed artery. On repeating the stretching
the curve is like that of a relaxed artery
throughout. As the difference between con-
tracted and relaxed arteries depends on the
muscular element, it is much more evident
when transverse rather than longitudinal
strips are used. The increments of cubic
capacity of relaxed arteries, just as of veins,
when subjected to equal increments of in-
ternal pressure, is greatest at first, and suc-
cessively diminishes as the pressure is raised.
On repeating the distension a second time
the relaxed artery is found to yield much
more.

Contracted arteries, on the other hand,
yield relatively little at first, and go on
yielding with each increase up to very high
pressure, but only very gradually. The dis-
tension of an artery whose muscular coat is

Fic. 10.—Elongation of
: : ; relaxed artery with rise of
thin augments up to a certain point, and _ internal pressure. Length

21 mm.
then becomes less as the muscular resistance ~~"

is wholly overcome, and the elastic elements come into play.
Second distensions of contracted arteries cause much greater ex-
pansions. MacWilliam says that Roy’s conclusion which has been
generally given in the text-books—that maximum distensibility

|

0 4. 60 80 100 20 10 160 180 200 220 B40 260 80 300 320 340 360 380 400 420

Fig. 11.—Carotid (ox), strongly contracted (48 hours p.m.). Increase in
capacity on rise of pressure.

of arteries corresponds to normal blood pressure—was based on
experiments with arteries more or less in a post-mortem state
of contraction. Fully contracted muscular arteries and relaxed

120 THE VASCULAR SYSTEM

arteries both give results wholly different to those of Roy.
MacWilliam finds that there is a great tendency to elongation,
in the case of relaxed arteries, when submitted to even low or
— moderate internal pressures.
Prolonged and frequently
recurring periods of relaxa-
tion tend, he says, to pro-
duce tortuous arteries ;
0 8 4 GO 80 100 120 140 160 180 20 20 #0 hence the tortuosity of the
Fic. 12.-—Carotid (ox), weak contraction anastomotic arteries which

(5 days p.m.). Increase of capacity. dilate after the ligation of

a main trunk, and of the arteries of the uterus and mamme |
{

which develop so in size during pregnancy, and the extensive
pulsation of arteries in inflamed parts. The pulsatile expansion
of a contracted artery is very small at any pressure, and there
is no evident difference in its amount at different pressures.
Hence the assertion of the surgeon
is explained, that there is no evi-
dence of the transverse expansion

of an artery when exposed and aie a ee oe
measured with callipers (Lister). 9 ” # % & 100 20 Ho 10 10 200
On the other hand, the pulsatile FI, 2%, =, Caotld (or). relaxed,
expansion of a relaxed artery for several days. Length (between
font given pulse at 0: Mimi. He, ligatures) 14 mm. ‘Increase of capacity.
50 mm. Hg, and 100 mm. Hg is in the proportion3:2:1. The
measurements taken by Roy and others, which show the
extensibility of arteries to be increased in pathological states,
such as marasmus and phosphorus poisoning, in the light of
MacWilliam’s work, must be interpreted by showing that the

—

Oo 8 40 6 8 0 120 40 160 180 200 220 240 260 280 300 320 H40 360 360.400 420
Fie. 14.—Second elevation of pressure in same portion of artery as in Fig. 12.

muscular rather than the elastic elements are at fault, and —
. that the power of post-mortem contraction is lacking. The
extreme degree of contraction produced by exposure and manipu-

AND BLOOD PRESSURE 121

lation is of the greatest importance in stopping hemorrhage from
wounded arteries; the abolition of contractility produced by
freezing explains the extra hemorrhage which results after freezing
has been used as a local anesthetic for minor operations. The
contraction of excised arteries, says MacWilliam, is excited by
chloroform vapour and adrenalin, and abolished by sodium
fluoride. It is a vexed question how far the extreme degrees of con-
traction, such as may be excited post mortem, may occur in living
arteries in continuity under the influence of drugs, or in disordered
states of metabolism. The view has been put forward that such
contraction does occur, and that the arteries become so rigid in
consequence of it, that serious errors arise in the reading of blood
pressure by the accepted methods. It has been asserted that in
cases where high readings of blood pressure have been recorded
much of the pressure has gone in compressing the stiff walled
artery.

THE ARTERIAL PRESSURE IN MAN

There are two methods at our choice for measuring the arterial
pressure in man. The one, the method of obtaining the maximal
oscillation and reading the pressure at which this occurs. ‘The
other, the method of finding the pressure at which obliteration of
the artery occur and the pulse ceases to be felt. The instrument
4 hitherto! generally used is the armlet, independently invented
by Riva Rocci and by Hill and Barnard, which consists of a
rubber bag encased in soft leather. The rubber bag is connected
by tubing and T piece to a syringe bulb and a manometer; the
latter may be either a Hg manometer or some form of spring gauge.
{ Several forms of sphygmometers have been invented by
v. Basch and others for application to the radial artery. Small
rubber bags are used and connected with metal spring gauges.
The graduation of such spring gauges alters with time, and the
writer finds small bags cannot be applied so that the pressure
always wholly reaches the artery. Some of it may go to distending
___ the elastic wall of the bag or to distorting the surrounding tissues,

and thus large and unavoidable errors arise with the use of these

instruments. The rubber bag must be large enough to transmit
pressure equally to all parts of the tissues in which the artery lies ;

then the tissues—protoplasm contains 80 per cent. of water—
' transmit the pressure 7d to the artery. The bag must be

ae
a
‘ *

122 THE VASCULAR SYSTEM

flaccid, and so closely confined by a rigid covering that the pressure
cannot be spent in distending its wall rather than in compressing the tis-
sues. The armlet satisfies all the requirements if it be large enough
(20 cm. broad), and be bound round so as to closely fit the arm.
The writer has introduced a sphygmometer which gives the
same readings as the armlet, and can be carried conveniently in
the pocket. It consists of a flaccid rubber ball enclosed in a
silk cover, and a gauge which can be carried in a case like that
of a clinical thermometer. The gauge is formed of a glass tube
closed at one end and having a hole in the side near the open
end. If the open end be placed in water, the water meniscus
rises as far as the hole in the side.1 The rubber tube of the
bag is then slipped over the gauge until this hole is covered.
On now pressing the bag the meniscus rises up the gauge and

compresses the air before it. The air acts as a spring, and the -

stem of the gauge is calibrated in mm. Hg by testing it against
a Hg manometer. To use the instrument properly the bag must
be only partially full of air, and must be entirely covered with
the fingers and palm of the hand, and then pressed upon the
radial artery, the thumb of the hand exerting a counter pressure
against the back of the wrist.2, The arm must be held at the
same level as the patient’s heart apex to eliminate the influence
of gravity, and the radial artery must be felt with the fingers of
the other hand, the second finger being employed to prevent the
pulse regurgitating from the ulnar, while the first finger deter-
mines when the radial pulse disappears. The operator, when
setting the index, holds the gauge by the solid glass end, so that his
fingers may not heat the air within. The gauge when taken out of
the pocket must be cooled to room temperature before it is used.

The instrument may be used, but not very easily, to obtain
the maximal pulsation. To effect this as little air as possible
must be used in the bag, and the bag must be closely confined to
the hand. There is some debate as to when maximal pulsation
occurs. According to Roy and Adami, and to Howell and Brush, it
occurs when the pressure just exceeds the minimal or diastolic
pressure as recorded by a Hiirthle manometer connected directly
with the artery. Hill and Barnard, however, found when the armlet

1 If water gets into the side hole it must be blown out, or else the meniscus will
not rise.
* The fingers grip the junction of tube and gauge and support the latter.

AND BLOOD PRESSURE 123

was placed round the neck of a dog, the maximal pulsation corre-
sponded to about the mean pressure as indicated by a mercurial
manometer connected with the femoral artery, and C. J. Martin
supported this finding. If the pressure just exceeds diastolic
pressure the artery should fill in systole and be emptied in diastole.
It takes time to do this, and when the pulse is frequent and the
pressure oscillations are large, not only is a very rapidly acting
instrument required to follow accurately the pulses, but there may
not be time for the full swing of the
artery to be carried out. Thus in
aortic regurgitation the maximal pul-
sation extends over a wide area of
pressure. It is owing to this that
divergence of opinion arises as to
what the maximal pulsation indicates.
The obliteration pressure, on the other
hand, unquestionably indicates the
maximal or systolic pressure, and the
only error which can arise is that due
to rigidity of arterial wall, if the
instrument be properly used. v. Basch
and C. J. Martin found that a
sclerosed radial artery is collapsed
by a few millimetres of mercury.
The writer found the carotid of a
child collapsed by 2 mm. Hg.

Herringham and Womack, inves-
tigating a number of arteries taken
from the post-mortem room, found 4
to 18 mm. and in two cases 30 to
34 mm. The pressure required bore
no relation to the age of the men
from whom the arteries were taken ;
the varying amounts were probably due to post-mortem contrac-
tion, a conclusion which is confirmed by the fact that the two
brachials in one case differed as much as 10 mm. Hg.

W. Russell and G. Oliver disbelieve the readings of the armlet
method in the case of contracted and sclerosed arteries. Russell
says he has felt arteries in life almost as brittle as glass, in other
cases rigidly contracted. He thinks it impossible that the high

4.JU.HIGKS SOLE MAKER LONDON. PATENT.

Fic. 15.—The
Leonard Hill
sphygmometer.

MF Ba B4 BG BG ba 24 BS BA De

SE SS

124 THE VASCULAR SYSTEM

blood pressure, e.g. 250 mm. Hg, obtained, should be endured by
the circulatory mechanism. As to the question of brittle arteries,
in order that the obliteration method should fail, the artery must
be rigid in the whole of its course enclosed by the sphygmometer.
Rigid atheromatous patches with soft parts between would not
disturb the readings. On inquiry among clinicians and patho-
logists the writer has not obtained from them evidence of the
existence during life of such rigid contracted arteries as W. Russell
describes. The post-mortem carotid of the ox, contracted maximally
by mechanical irritation, feels as if it would require some pressure
to obliterate it. What pressure is required the writer has not suc-
ceeded in ascertaining owing to the difficulty of putting the whole
length of the artery which is enclosed in the gauge in a state of
such contraction. G. Oliver finds in states of sclerosis considerable

differences between the armlet readings and those obtained with his .

hemodynamometer,—a metal spring gauge used with a small fluid
pad on the radial artery,—and believes that the maximal pulsation

index thus obtained is the safer guide because it necessitates, not

the obliteration of the artery, but only the balancing of the pressure
wave. Now the maximal pulsation method shows two maxima,
one corresponding it is said to the diastolic pressure and the
other to the pressure which obliterates the artery, i.e. the systolic
pressure. The second maximum is produced by the pulse wave
striking against the upper edge of the pad or bag, and diminishes
when, as the pressure is lowered, the systolic wave just slips through
the artery (Erlanger).

Oliver prefers this index to that of pulse obliteration. He
gives readings taken from the arm and forearm, on the two arms
of the aged, by the obliteration method, and adduces the variation
of these as evidence that the method of obliteration is liable to
error. Thus—

Woman Recumbent, 90 Years old.

exes ap repeat had Armlet Obliteration Method.
; ., 1108 130 8 140 S
Right side, 95 D Forearm, 35D Arn, - oD.
: 1108 1458 180 S.
Left side, 05 D = ED | a

Oe

AND BLOOD PRESSURE 125

Woman Recumbent, 93 Years old.

—- Sete Ieee pee
gy Sem agree Armlet Obliteration Method.
’ so
soos, 1868 | 175 8 a 1908
Right side, iD | Forearm, 125D Arm, 130D
oc NSS 155 S 180 S
Left side, ib | a TED » TAD

The writer, however, investigating the accuracy of small un-
enclosed sphygmometer bags, has come to the conclusion that they
introduce grave errors. The pressure may not be transmitted by
them to the artery, but go to displacing surrounding tissues, or to
stretching the rubber bag. The bag must be big, must be flaccid,
and must be entirely enclosed by a rigid casing, e.g. the hand, or
leather cuff of the armlet. Oliver’s hemodynamometer appears
to him not free from the errors which pertain to small unenclosed
bags.

In seventeen out of the eighteen ‘ diastolic” readings taken
with the armlet cited by Oliver, the readings are almost the same
(within 5 mm. Hg) on forearm and arm, or right or left arm.’ On
the other hand they exceed by 15 mm. Hg, in all except one case,
those taken by the hemodynamometer. This suggests the inaccuracy
of the latter instrument, for the maximal pulsation index of the
armlet method has been tested against the blood pressure of dogs.
The writer has found the systolic pressure of old people may vary
with the different strokes of the heart, and in the young with
emotional excitement, and as the obliteration method gives us
the maximal stroke in any period, it is necessary to test the armlet
method by having two instruments at once on the opposite arms,
with two observers reading at the same time. Doing this Martin
Flack and the writer have found the readings taken by the ob-
literation method to be the same, not only in normal people but
in several cases of high pressure (180 to 230 mm. Hg) and of
thickened arteries. They have also taken the pressure with one
arm up and the other down, and found that the difference corre-
sponds to the pressure of the column of blood separating the top
of one armlet from the top of the other—top meaning the part
next the shoulder. If the rigidity of the arterial wall came

126 THE VASCULAR SYSTEM

seriously into play we should not expect this correspondence, for
it is unlikely that the arteries on the two sides would be equally
degenerated and rigid. It is also unlikely that they would be
equally contracted, because an artery exposed to lessened blood
pressure dilates, while to increased blood pressure it contracts.
We should expect, therefore, the artery in the upraised arm to
be less contracted than the other. In one case of aneurism they
were quite unable to make these tests owing to the greatly varying
inequality of the heart strokes. Tested on the thigh of dogs both
the armlet and the writer’s pocket sphygmometer gives the same
readings as the opposite femoral artery taken directly with cannula
and manometer.

The conclusion the writer has come to, then, is that the method
is exact, when carried out with either the armlet or the large

enclosed bag of his pocket sphygmometer, and that these are the .

simplest and best methods of testing the systolic arterial pressure
in man. The first act of obliteration must relax the artery and
make subsequent readings exact.

It has been suggested that during obliteration of such a large
artery as the brachial, the general arterial pressure may rise, but
no error arises thus, if two or three consecutive readings be taken.
The readings should be taken when the excitement and novelty of
the operation has passed off, as emotional excitement raises the
pressure considerably. Thus the writer’s pressure in the morning
is 110 to 115 in the holidays, and 140 when teaching and working
in the laboratory. He has observed the pressure to rise 10 mm. Hg
on addressing a question to the subject. There is no advantage
gained by reading the pressures nearer than within 5 mm. Hg, or
in the use of complicated instruments for recording the maximal
oscillations, such as that of Erlanger.

The average systolic\ pressure of the resting man according to
a number of observations taken by H. J. Starling is—

15 to 40 years ; ; ‘ ; 119
41 to 60 ,, 3 - - 142
6land over . 2 ; : 155

but some robust old men, he says, have pressures no » higher than
those of the young.

The writer has found the pressure to be as low as 80 mm. Hg
in children ; to be 80 to 110 in young adults ; and to be no higher

—_—

AND BLOOD PRESSURE 127

in several active men, eminent in their walk of life and carrying some
60 years. Oliver gives armlet systolic readings of 135 in a man of 100
years, and 185 to 190 in a woman of 96 years, and says: “‘ In women
the pressures are generally 5 to 10 per cent. less than in men.”
M‘Cay of Calcutta says the pressure there varied between
83 and 118, and the average of a large number of observations
was slightly over 100 mm. Hg (sitting position, arm level with
heart). The low pressure there he attributes to the hot climate
relaxing the cutaneous vessels. In the standing posture the
arterial pressure is no lower, and may be higher, than in the hori-
zontal posture, and this without more than 5 to 10 extra pulse
beats a minute. In exhausted states the frequency of the heart
may be 30 or 40 more in the standing posture, and yet the pressure
be lower than in the horizontal position. The change of pulse
frequency with posture is an excellent test of the vaso-motor tone.
The diastolic pressure in the small arteries, such as the
phalangeal, has been measured by G. Oliver by applying a small
bag (2°5 em.x9 cm.) round the third phalanx of the middle or
ring finger or the second phalanx of the thumb, and raising the
pressure till the maximal pulsation is obtained and felt by the
patient. To obtain the systolic pressure the finger is rendered
bloodless by squeezing a stout rubber ring over it as far as the
lower edge of the bag ; the pressure in the bag is then raised to over
100 mm. Hg, the ring removed, and the pressure lowered till the
bloodless finger suddenly flushes (Girtner). The lower range of

readings so obtained by Oliver are pie a 4 the higher og -

On the arm, he says, there is no difference in pressure between
the brachial and radial arteries, but the pressure in the phalangeal
artery at the level of the first phalanx is 10 to 25 mm. less, and at
the level of the third phalanx the pressure is a little less than half
that in the big arteries. Thus the fall is unnoticeable in the big,
and rapid in the small arteries. In the latter too the systolic and
diastolic pressure approximate more and more. The ingestion of
food, according to Oliver, raises the arterial pressure in the distal
area; the pressure in the last phalanx rises 15 to 20 mm. Hg
within an hour of taking food, and then slowly sinks down again.
Exercise raises the arterial pressure. In athletes immediately after
races the writer found systolic pressures of 140 to 220 mm. Hg.
The pressure falls markedly with over exhaustion. Thus after four

128 THE VASCULAR SYSTEM

exhausting bouts of boxing the pressure fell from 160 at the end
of the first bout to below 100, and rose to 130 after three minutes
rest. Inhalation of oxygen, then, lowers the pulse-rate and raises
the blood pressure, changes the respiration from the thoracic pressure
to the abdominal type, and restores the vigour of the athlete.-
The heart seems to be poisoned by unoxidised products such
as lactic acid during extreme efforts, and therefore the com-
pressive action of the diaphragm is held in check (L. Hill and
M. Flack). After exercise the brachial pressure falls, while the
phalangeal pressure remains higher owing to vaso-dilatation and
for some time particularly if the subject is heated by exercise

(Oliver).

THE VENOUS PRESSURE

Oliver presses the pad of his hemodynamometer onaselected vein _

of the back of the hand placed at heart’s apex level; next empties
the blood by stroking it on past the next valve; then relaxing the
pressure, notes the point when the vein just refills. The writer
and M. Flack have tested the method by applying the armlet to the
upper arm, and raising the pressure within it to say 60 mm. Hg.
The pressure in the veins below the armlet must then rise to
60 mm. Hg. Employing small bags in accordance with Oliver’s
method to test the pressure in the superficial veins, they have found
that they cannot be used accurately. A second armlet, however,
can be so used. This is placed round the forearm, and the pressure
raised above that in the veins, say to 70. The pressure in this
is then relaxed till some selected vein above this armlet, which
has been stroked empty up to the next valve, just refills; thus an
accurate reading of the venous pressure is obtained. Employing
the two armlets, they found the venous refilling pressure exactly
corresponded to that in the upper armlet which was obstructing
the venous return. A convincing proof of the general accuracy
of the armlet method can be gained by this method thus—find
the obliteration pressure for the brachial artery—say it is 150—
lower the pressure to 145 so that blood can get through, and then
find whether there is the same pressure, viz. 145, in the superficial
veins. If so, it is clear the arterial reading is correct within 5 mm.
They have done this in several cases, and in one where the
arterial wall felt full of stiff sclerosed patches, and have found no
evidence that the arterial wall influences the readings.

AND BLOOD PRESSURE 129

Another method of Oliver’s is to place the hand, with the
fingers extended, in the upright position and at the level of the
heart’s apex, taking care that the veins are not compressed by
clothes or the posture of the arm. He then observes the veins

«on the back of the hand, and raising the hand until the veins just
collapse, measures the vertical height of the veins above the apex
of the heart. This measurement gives him the venous pressure in
millimetres of blood. The method demands that the veins should
be visibly distended, which may not be the case in a cool atmos-
phere. The venous pressure varies with warm or cold atmosphere,

- with posture and muscular effort, pressure of the arm against the

body, pressure of clothes, &c., on the arm, and taking of food.
When the veins of the hand are contracted down with cold, we
cannot tell what positive pressure there is in the veins at the heart’s
apex level by either of the above methods. The veins contract
down to the thread of blood which they receive when the atmos-
phere is cold, and dilate to hold a large volume of blood when
brought into play as a part of the heat-losing mechanism of the
body. The best demonstration of this is the network of super-
ficial veins which become visible in a child in a hot bath, or a
horse heated with work.

If the hand be held at such a level that the veins are just
collapsed, and then deep and prolonged expiratory efforts or a
succession of coughs be made (Oliver), they will be seen to swell,
and this is owing to raised arterial pressure and little if at all to
obstructed venous outlet (T. Lewis). Prolonged inspirations, on
the other hand, cause the visibly swollen veins to vanish. The
influence of posture is seen on holding the hand and arm still
in the dependent position, particularly in a warm atmosphere,
or after exercise, or food. The veins fill under the hydrostatic
pressure, and the colour of the hand becomes bluish owing to the
lessened velocity of blood flow. A dull feeling of pressure arises
which is uncomfortable and causes one to move the part. Con-
traction of the muscles of the hand empties the blood in the

_ capillaries and veins on past the valves, and so long as the hand

4

is at work no distension or discomfort arises. If the hand be

kept quite still at the level of the heart’s apex little congestion

arises. How much bodily movements further the circulation of

_ the blood can be seen by alternately placing the hand dependent,

and elevating it above the head, and observing how the hand
I

=

130 THE VASCULAR SYSTEM

changes from the flushed to the blanched state. The vaso-con-
strictor control of the hand (for changes of posture) seems to be
much less than that of the foot. If in a warm atmosphere foot and
hand be lowered together from the heart’s apex level and be kept
still in the dependent posture, it will be seen that congestion arises
much less quickly in foot than in hand, and the pressure in the
veins on the back of the hand reaches the full gravity effect much
sooner than in the veins on the dorsum of the foot. It is the same
with the face. The parts always exposed to the atmosphere
congest quickest. The control of course varies with the effect of
external temperature on vaso-dilatation, as may be seen by plung-
ing the hand and foot in iced or in hot water and then repeating
the observation. The pumping action of the movements of walk-
ing may be observed very well on the veins of the back of the
foot. Let the reader stand still with the feet bare, and observe _
the veins of his feet becoming prominent. If he bend to feel them
he can estimate the high pressure within. Now let him take a
few steps and observe the veins again. They are emptied by the
movements, squeezed between skin and muscle, and feel soft for
some little time until they fill again on standing still. Similarly
the contractions of the muscles which occur with slight changes
of posture empty the veins and prevent congestion when we sit
working at a desk. It is the deficient flow or quality, not the
pressure, of blood which leads to cedema, degeneration, distension
of the venous wall, and varicose veins in those whose occupation
requires them to stand for long periods of time. Some attention
has been drawn to a curious hereditary oedema of the legs which ~
commences about the seventeenth year. It occurs in members
of certain families on standing, and is prevented by bandaging.
The venous pressure is raised, owing to vaso-dilatation, by warmth,
rest, sleep or food, together with the pressure in the arterioles as
measured in the distal phalanx, while the pressure in the large
arteries falls. The arterial and venous pressures in the arm are
both raised during muscular effort, owing to increased ventricular
output, splanchnic constriction, and local dilatation.

THE CAPILLARY PRESSURE

As much light can be thrown upon the principles which govern
the circulation of the blood, from the comparative structure of
j :

°

AND BLOOD PRESSURE __ 131

the vascular systems, the writer cites the following suggestive
passages from the admirable Principles of Animal Histology of
Dahlgren and Kepner, in which he underlines certain sentences
which bear in particular on the arguments that follow.

“The main blood channel system itself has many differentiated
régions. The region of thin-walled capillaries and lacune, the
strong-walled conducting vessels, the blood-forming organs, and
the muscular pumping stations or hearts . . . most specific of these
portions are the capillaries and lacuna, for it is here that the real
; work of the blood is accomplished, the exchange of material with
; the tissues. Here the walls of the vessels are thinnest or even

apparently wanting. In this case the connective tissue cells that
surround the channel, while not differentiated into definite channel
walls, act in that capacity, so that we cannot say that retaining walls
are altogether absent. The vessels of the periphery have in all cases .
a larger total cross section than any other total cross section in
the circuit. This results in the surface of contact between blood
and tissue being large enough to effect necessary exchanges of
materials as well as making the circuit slower to give requisite
time for such exchanges. The smaller but more numerous branches
of the periphery unite to form large channels that serve to conduct
the blood to other portions of the periphery, or to and from the
central pumping stations, or to the blood glands. These vessels
and the veins, together with the vessels carrying blood back to
the periphery, the arteries, act as the long-distance carriers of
the circulatory system, and their walls are usually very strongly
constructed.

“The pumping region comprises one or more parts of the larger
channel or channels that have acquired the power of rhythmic
contraction. Sometimes this region occupies a considerable
extent of the larger vessels. At other times it is found in a more
{ specialised form, occupying only a short section of the tube, but
very intensely developed. Such an organ is known as a heart.
Both of the preceding conditions may be found together, as
they are in the squid and other cephalopod molluscs where there
_ __ are three or five separate hearts, and in addition the larger parts
of the arteries are also constantly engaged in driving the blood on its
course by wave-like pulsations. Other regions of the blood-channel
_ system are found in which the walls are differentiated and in which
_ the blood moves but slowly and sometimes almost comes to rest.

132 THE VASCULAR SYSTEM

These form the so-called blood glands, and in them the blood is
renovated by the removal of some of its old parts and the addition
of other new ones or both.”

“ The internal tissue of a Turbellarian worm is a loose aggregate
of several kinds of weakly differentiated cells, known as parenchyme.
These cells do not touch each other at all points, but are connected by
strands, and in consequence there may be easily seen between them a
great many spaces, known as the intracellular spaces, which are united
into a large connecting system that extends throughout the body. This
system of spaces is filled with a fluid, and this fluid carries the digested
food materials, the oxygen supply for internal cells, the combustion
products, and in every other way acts as a simple blood. This is the
undifferentiated and unorganised form of blood-vessel system, and a
sort of circulation must inevitably take place as a result of the ordinary
movements of the animal’s body. This grade of structure is to be |
seen in a number of the lower and simpler animal forms and some-
times as an accessory apparatus to several grades of complete blood-
channel systems.” In the several typical forms studied by Dahlgren
and Kepner, the walls of the blood channels show a strong analogy
based on the physiological (which are here mechanical) needs of
the vessels. The blood fluid must be confined to the channels,
and this is usually done by the single inner layer of cells, the intima.
In some forms the intima is formed not by the cells themselves
but by a cuticle which is the product of these cells (lobster, &c.).
‘The intima may alone confine the blood stream, or if the pressure
is too great, it may be reinforced by the connective tissue cells
that immediately surround it. These cells develop their connective
tissue as fibrils or plates or webs with which they bind and hold the
vessel intact when the blood presses on its walls. Again, these
primitive mesoderm cells may develop into muscle cells that sur-
round the channel and by their contractile strength cause it to
pulsate and drive the blood on its course. The arrangement of
these three classes of tissues to form the wall of the vessel falls,
naturally, into layers, the so-called coats of the blood vessels.
Each kind of coat usually has a particular position with reference to
the lumen. This position, however, is sometimes changed in the several
groups for no apparent reason, All these cells and the tissues that
they form were probably not cells that were bound in the course
of their development to become so specialised, but as far as can
be told, they were such of the connective tissue cells as happened

AND BLOOD PRESSURE 133

to be in the course of the developing blood channel as it pushed
its way among them, and were developed in response to the needs of
the vessel.” .

The first capillaries in the area vascular of the developing
; chick have their origin in the secretory activity of the cells which
first form vacuoles and finally networks of capillary spaces. It is
the functional activity of the cells which determines the rate of
flow and pressure within, and finally the structure of the vessels
and of the power of the heart. The increase in size of the lumen
of a vessel, says Thoma, depends upon the rate of blood flow.
Hence the dilatation of collateral pathways and establishment of
efficient anastomoses which follows the ligation of a main artery.
The growth in thickness of the vessel wall is dependent upon the
diameter of the lumen of the vessels and the blood pressure. The
tension in the circular direction of a tube is equal to the product of
the pressure by the radius. The longitudinal tension is equal to
half this product. The wider channels first formed in the area
vasculosa thus develop into arteries ; collateral capillaries develop
into arteries when a main artery is tied; and the thyroid vein
develops the structure of an artery when the central end of the
carotid is joined end to end on to it.

Thoma states that at all points where the transverse sectional
areas of the lumina of the arterial trunks has been investigated
the sum of the sectional areas of the main trunks is equal to that
of their branches. Thus the sectional area of the ascending aorta
equals the sum of that of the two carotids, and subclavians and
the descending aorta, together with such smaller-branches as were
given off above the place of measurement. Similarly the sectional
area of the abdominal aorta taken 2 cm. above its bifurcation
is equal to that of the two common iliacs and the smaller
branches. The same law holds good, Thoma says, in the case of
the arterioles of the tongue or web of the frog. As, he says, the
transverse section of the main artery is equal to the transverse
section of all its branches, the average rate of flow is the same
in all arteries, and the quantity flowing through the transverse
section of any artery in a given time is proportional to the section
of the artery. This law only holds good so long as disturbing
influences due to vaso-dilatation and functional activity are in
abeyance.

That the ramification of the small arteries is homonomous

134 THE VASCULAR SYSTEM

is proved, says Thoma, by the microscopic observation of the axial
stream. The stream of corpuscles moves so fast that it appears
either completely homogeneous or faintly striated, both in the
artery and its branches (excluding the capillaries), and thus must
be flowing at the same rate, for the slightest diminution alters the
homogeneity. When the tongue of a frog is drawn forward from
the mouth of a curarised frog and pinned out for examination,
there follows at first considerable deviation from homonomous
ramification, owing to injury and local dilatation. Half-an-hour
later the tongue is hyperemic, but the flow 1 is again of the same
rate in all the arterial ramification.

The generalisation follows on these observations of Thoma
that the total cross sectional area of the arterial ramification
measured at any place is the same,! and that the sudden increase

occurs in the ramification of the capillaries, so that the rate of

flow is lessened therein from 500 mm. to 3} mm. or less a second.
This important generalisation, so opposed to accepted teaching,
requires confirmation or refutation.

The capillary system in the tissues of man is like the blood
channel system of the Turbellarian worm, a vast system of tissue
_ spaces lined by cells which confine the corpuscles, and by shrinking
or swelling and by varying osmotic state regulate in part the
outflow and inflow of lymph. These cells are capable of phagocytic
action and of dividing and producing the primary type of leucocyte.
The arteries deliver the blood to these spaces. and many or few of
them are filled at any moment and in any tissue according as the
arteries dilate and increase the supply, or the venous flow is im-
peded by gravity or external pressure. It is absurd, therefore, to
calculate the size of the capillary bed from the relative velocity in
the aorta and in the capillaries of a transparent membrane.

The cells both of the tissues and the capillaries swell or shrink
under:the influence of the solutions which bathe them, and thus
alter both the volume of the organ and the capacity of the vascular
system which is included in it. The tissue cells adapt themselves
slowly to altered osmotic conditions of the tissue fluids, and do
not by any means come into equilibrium with them. With the
return to normal physiological relations the recovery of the normal
concentrations of the cellular contents is rapid and complete.
The influence on the capillary circulation of osmotic and surface

1 Supposing the state of constriction to be the same. .

— -

AND BLOOD PRESSURE

energy can be no less than that effected by the heart and vaso-
motor system, and is, probably, as important in controlling the
flow of blood. In the active conditions of life the contents of
the capillaries are continually being emptied onwards by the
contractions of the skeletal muscles, pressure against external
bodies, and the influence of gravity in changes of posture. The
capillary system is as a sponge squeezed and filled continually by
the active motions of the body. The attempts which have been
made to estimate capillary pressure have all been made on trans-
parent membranes in the motionless animal fixed in the horizontal
position, or on man’s skin with the part fixed, immobile during
the observation. In the animal microscopic observations have
been made by Roy and Brown on the frog’s mesentery, the
capillaries being compressed by a sheet of transparent peritoneal
De membrane which formed the base of a glass capsule, in which the
f fluid pressure could be made greater or less. A pressure of 100
7 to 250 mm. H,0 sufficed to stop the circulation in the capillaries
under these conditions, while a pressure of 200 to 350 mm. H,O
__ expelled the blood from the arterioles. When the heart was in-
hibited the pressure sank to 0, rising again to 70 to 100 mm. H,O
as the veins filled. The anemia so produced was followed by
| hyperemia and increased pressure.
+ Measurements of capillary pressure have been made on man
by v. Kries, v. Recklinghausen, and others, the method being the
finding of that pressure which just blanches the skin. V. Kries
weighted a glass plate 4 sq. mm. big placed behind the finger nail.
He found 0°25 grm. was the smallest difference which produced a
visible effect. Now as 1 grm. equals the weight of 1 ¢.c. of H,O,

135

1 and Taam." 1 250 mm., the error of observation would be
ian =62°5 mm. H,O, a very large one considering the smallness

of the pressure measured. H. W. Recklinghausen places a small
flaccid rubber bag on the skin, through the centre of which he has
punched: a hole. He moistens skin and bag with glycerine, and —
covers the hole with a glass slide, holding it so as to make an*air-
_ tight junction between bag skin and glass, and then through a
side tube blows air into the bag until the skin blanches. A mano-
meter connected with the side tube gives the pressure. These
methods necessitating the fication and immobility of the part, cannot
be applied rapidly, and therefore do not give the capillary pressure

136 THE VASCULAR SYSTEM

under ordinary conditions. Moreover the pressure so applied is
spent largely in deforming the horny convex plate of the epidermis,
and in the case of v. Kries’ method the size of the horny layer
which is depressed is much larger than the square glass plate.
This can easily be seen by taking a set of broom bristles and fasten-
ing them to matches in lengths of about an inch, and then finding
the bristle which will just blanch the skin when pressed on it till
it bends. It can be seen that the bristle depresses a horny plate
selected, say, on the back of the hand, much larger than its own
sectional area. If some of the horny layer be carefully removed
with a razor (without producing hyperemia) a weaker bristle will
effect the blanching. Observations of this kind show that these
methods are too inaccurate to use as a measure of capillary pres-
sure ; nor can they be used to give exact comparative differences of

pressure under varying conditions, for the error cannot be taken °

the same all through. V. Kries found that the blanching pressure
at the root of the nail did not give the full gravity effect on change
of posture. Here the time of fixation in any posture is an im-
portant and undetermined factor.

Difference of Level of Finger

from Top of Head in mm. Pressure in mm. H,0.

0 328
205 397
490 513
840 738

Lewy has calculated the pressure required to overcome the re-
sistance in the capillaries from the known facts concerning pressure,
velocity, and the viscosity of the blood. The average length of the
capillaries is 0'4 to 0°7 mm., their radius 0°0045 mm., and velocity
0°5 to 0'9 mm. per second. There flows per second through a capillary
a quantity varying from 7 x 0°5 x 0:0045? up to = x 0°9 x 0°0045? c.c.
From the Poisemille formula—determined for flow in capillary glass

tubes—Q = K x Ls where Q=the quantity per second, / the pressure

difference between beginning and end of tube, d the diameter and / the
_ length of the tube, and K a constant representing the coefficient of
viscosity, from this formula Lewy calculates h to be equal to 10 to
150 mm. of blood. The mean arterial pressure being taken as 115 mm. Hg
or 1500 mm. of blood the fall of pressure in the capillaries is 45 of this

AND BLOOD PRESSURE 137

at the least or ,'; at the greatest estimate. So wide a difference makes
the calculation of little value except as an indication of the fact that
there is little resistance in the capillaries. In making such estimates
the velocity of flow in the capillaries is observed in their membranes
with the animal motionless and in the horizontal posture. We have,
moreover, no reason to think that the same laws hold good for glass
tubes and the living capillaries. The cross section of a capillary 10p
in diameter is some yz}y5 8q- mm., the outflow per second will be
rztoo x $ if the velocity is 0°5 mm. per second, or 1 c.mm. in about
six hours, or 1 c.c. in 250 days (Stewart).

The writer has measured the capillary-venous pressure in the
brain by finding the pressure which just overcomes the pressure
_with which the brain bulges into a trephine hole. The “ brain
pressure ” is due to the blood pressure in the capillaries and veins
which is left over after the resistance in the arteries has been over-
come, and distends the brain substance. When the circulation
ceases the brain collapses away from the trephine hole and no
longer exerts any pressure. The intra-cranial pressure cannot be
greater than that in the pial veins, for otherwise these would be
obliterated, and the pressure within them must then rise to the
intra-cranial pressure. Observation can be made by screwing a
glass tube into the trephine hole, the tube being filled with water
and closed by a flaccid thin rubber membrane at the brain end,
and connected to pressure bottle and manometer at the other end.
An air bubble is introduced into the glass tube to mark the zero
7 pressure. When the tube is put in place, the air bubble is pushed
? outwards, and on raising the pressure bottle and pushing it back
# to zero the “brain pressure” is balanced and the manometer
indicates its amount.

In the horizontal anwsthetised animal the “ brain pressure ”
is about 100 mm. H,0, sinking even to 0 in the vertical head up
position, and rising considerably in the vertical head down posture.
The cay‘'lary pressure in the brain varies proportionately with the
rise and fall ot vena cava pressure—time being granted for the
_ capillaries to follow the alteration of venous pressure. The brain
pressure does not follow in exact proportion alterations of aortic
pressure, because between the capillaries and the aorta is placed
the varying resistance of the arterioles. The cerebral venous
_ pressure can be measured by inserting a tube into the torcular

-Herophili, and the pressure of the cerebro-spinal fluid (the lymph

‘.

138 ‘THE VASCULAR SYSTEM

of the brain) by inserting a tube through the lamina of the axis.
The brain pressure, the cerebral venous pressure, and the cerebro-
spinal fluid pressure are one and the same.

The writer has also measured the capillary-venous pressure in
the eyeball by the same method, inserting a hollow needle into
the aqueous. The globe formed by the corneo-sclera is analogous
to the rigid case formed by the skull because its internal capacity

is strictly limited, and cannot be increased. The intra-ocular

pressure, like the intra-cranial, is purely circulatory in origin and
represents the capillary-venous pressure within the eye. The venous
sinus of the canal of Schlemm, according to Thomson Henderson,
is formed of tributaries from the whole anterior portion of the
uveal tract, and it thus offers the lowest pressure with which the
aqueous humour comes into direct contact, just as the pial veins,

where they pass into the sinuses, offer the lowest pressure to the ©

cerebro-spinal fluid. The intra-ocular fluid, just like the intra-
cranial, transmits pressure equally in all directions, and therefore

when its exit is diminished the tension rises, and the whole of -

the elastic intra- vascular system tends to be converted into a
rigid one. —

Koster has proved experimentally the unyielding nature and
rigidity of the globe under conditions of increased intra-ocular
tension. If the internal pressure were raised from 19 to 70 mm. Hg,
the increase in volume of the globe was only y955 of the original
volume.

In the globe of the eye the capillary-venous pressure is the intra-

ocular pressure. The intra-ocular pressure in fact equals that in the ©

venous sinus of Schlemm’s canal, just as in the skull the pressure
of the cerebro-spinal fluid is equal to that in the pial veins.
Supposing the intra-ocular tension, owing to the increased

secretion of the ciliary process, rise above the pressure within

Schlemm’s canal, then the pressure of the aqueous will obliterate
the wall of the sinus until the venous pressure rises within it to

that in the aqueous. Similarly, supposing by increased secretion —

of the choroidal fringes in the brain the pressure of the cerebro-
spinal fluid rise above that in the pial veins, then these would be

obliterated until the pressure of the blood within them rise to that

of the cerebro-spinal fluid. Actual measurements show that the
pressure of the cerebro-spinal fluid and of the cerebral venous
pressure are the same.

- tiedtItz=p.=z=z Ve

—e ee = -. —

AND BLOOD PRESSURE . 139

If the arteries dilate in the brain or eyeball, room must be
‘made by increased outflow of cerebro-spinal fluid—or aqueous—or
by narrowing of the veins, or by both means. Probably each
pulsatile expansion of the arteries helps to drive a little of the
cerebro-spinal fluid or aqueous into the veins, and thus the effective
- circulation of these tissue lymphs is maintained. Each pulsatile
expansion of the arteries also causes a pulsatile expulsion of venous
blood into the venous sinuses and thus helps the circulation. A
rise of arterial pressure accompanied by expansion of the arteries
of the brain or eye, cannot compress the veins so as to produce
venous congestion or stasis, for the pressure transmitted through
the walls of the arteries must always be less than the pressure
transmitted directly through the blood within the vessels. The
veins are narrowed to compensate for the expansion of the arteries
- until the whole system becomes more like a rigid system, and the
-___ velocity of flow is increased, less of the head of pressure being spent
in overcoming the resistance in the arterioles, more going to the
kinetic energy of flow. Experimental observations show that the
- outflow is always increased by a rise of arterial pressure.
In pathological states the intra-ocular or intra-cranial pressures
are often increased. Such increase is entirely circulatory in origin.
In inflammatory states the toxins produced by bacteria on the
one hand dilate the blood-vessels, and on the other hand alter the
metabolism of the tissues, and increasing those cell products which
are crystalloidal in character, thus raise the osmotic pressure. The
tissues swell, and the blood pressure rises, keeping pace with the
* pressures of the tissue lymph. The swelling must be at the ex-
pense of the blood supply of other surrounding parts, where there
is no toxin to excite and no vaso-dilatation or edema. The
anemia so produced may in its turn damage the tissue metabolism
of these parts, and set up congestion and cedema therein, and thus
a vicious circle may be established. Relief is obtained by opening
or softening the confining capsule, and so allowing free flow of
blood and free exudation of lymph through the inflamed part.
The lymph brings with it neutralisers of the toxins, the phagocytes
and their opsonins, the chemical repairers of disordered cell meta-
bolism. If the products of tissue damage are successfully removed
_ by the increased flow in the surrounding dilated vessels the whole
mischief subsides, and the killed tissues are removed and replaced
_ by growth of scar tissue. During inflammation of such an organ as

140 THE VASCULAR SYSTEM

pneumococcus (Carnegie Dickson).

The author has borrowed these figures to show

y capillaries.

tance from tissue into blood-vessels may take place,

congested vein and its tributar,

bs

great]

how.large a transference of su

cage?
e" ¢ 2 xy

Fic. 16.—Transverse section of marrow of femur of normal rabbit and of one infected with

Note in the latter the

——————
:

AND BLOOD PRESSURE 141

~ the brain or bone marrow the amount of blood can be enormously

increased by the transference of tissue fluid and tissue substance
from the tissue cells into the blood channels.

The way in which increased tension may arise can be illustrated
by a consideration of the cause of glaucoma of the eye.

In glaucoma the cribriform ligament is sclerosed, and by wall-
ing in Schlemm’s canal prevents the free circulation of the aqueous
humour which is necessary for the proper metabolism of the eye.
When the cribriform ligament is sclerosed the aqueous has to get
away mostly by the veins of the iris through the iris crypts, and
thus it comes about that atropine induces an attack of glaucoma
by dilating the pupil and closing the orifices of the crypts of the

iris. Ividectomy, on the other hand, relieves glaucoma by opening

up new channels for escape of the aqueous, as the surface of
the iris never scars up, but remains open and unaltered after it
has been cut (Thomson Henderson).

The cedema of the tissues of the eye which occurs in glaucoma
may be ascribed to the deficient circulation of aqueous, leading to

altered metabolism and increase of osmotic pressure. The conges-

tion of the blood vessels must be also set down to the irritant
effect of the products of disordered metabolism. A rise of
general vascular pressure may, it is said, precipitate an acute
attack of glaucoma; probably by increasing the secretion of
aqueous; this finds room at the expense of the veins which
are narrowed, ¢.e. the absorbirig surface ; the excess of aqueous
cannot escape again when the general pressure falls, and thus the
tension of the eyeball remains heightened, the circulation in the
eye lessened and the mischief increased.

The conditions which hold good for the eye and brain also
apply in part to the limbs enclosed by the skin, and to the other
organs, such as the kidney, which are enclosed in capsules. The
writer and M. Flack estimated the capillary pressure in man by
pushing a hollow needle into the subcutaneous tissue of the arm

_ or leg, and connecting this with a glass tube containing an air

bubble, and the tube with an Hg manometer and a pressure bottle.
The air bubble indicates when the pressure is sufficient to over-
come the capillary pressure and drive the water in, and as the
subject feels the smart of the water, he can give a confirmatory
signal, The observations made in this way showed that a pressure

of 10 to 20 mm. H,O was sufficient to overcome the capillary

“

142 THE VASCULAR SYSTEM

pressure in the arm placed at the heart’s apex level. In the leg
at a level 380 mm. below the arm 90 mm. H,0 sufficed, giving
a difference of 70 mm. H,O against a gravity difference of
380 mm. H,O. On supplying the armlet and raising the pressure
in it to 910 mm. H,0O, the capillary pressure in the forearm rose to
45 mm. H,O, at a time when the venous pressure had risen to
that in the armlet. On another occasion it was 57 mm. H,0O,
and in the armlet and veins 910 mm. H,0.

These observations only prove what any one can feel for him- -
self by holding a limb motionless and dependent for some time
and then estimating with his finger the pressure in the veins and
the capillary areas of the skin. Every movement that occurs under
the varying conditions of active life squeezes on the capillary and
venous blood. The tissues and pressure sense organs are thus
protected from any great increase of vascular pressure. After an -
area of capillaries has been squeezed empty, the blood pressure
for a.time must be nil within it. The blanching effect of clenching
the fist demonstrates this. Thus in spite of the hydrostatic pressure
due to gravity, equal to 140 mm. Hg in a man six feet high standing
vertical, in spite of this the same bristle will blanch the capillaries
of his feet and hand, so. long as he does not keep the parts for long
immobile, but by contractions of his muscles every now and then
expresses the blood from the capillaries onward past the venous
valves. The vaso-motor system by constricting the arterioles—
the arteries constrict of themselves to increased pressure—prevents
over rapid filling of dependent parts, so that it takes some little
time for the dependent and warm immobile hand to become greatly
congested, and still longer the foot, while in a cold atmosphere,
owing to vaso-constriction, congestion is only very slowly pro-
duced by the dependent posture.

So that while arterial and venous pressure in a relaxed limb
exactly follow the variations of hydrostatic pressure on change of
posture, the capillaries do not. Likewise on obstruction of the
veins, while the venous pressure rapidly rises to the pressure of
the obstructing armlet, the capillary pressure rises only very
slowly. This fact which seems at first sight contrary to physical
laws, in that the pressure is high in the artery which feeds and in
the vein which drains but not in the capillary area which joins
together the two, this fact is explained if we suppose that the
capillary bed is a sponge work emptied by every movement, and

4
:

AND BLOOD PRESSURE 148

taking time to fill up again, and that there are wider channels
connecting the arteries and veins through which the pressure is
transmitted to the veins. The existence of such wide channels is
recognised by histologists. Inspection of the hand and foot when
kept still, and held first in the dependent, and then in the horizontal
position, when held in the dependent position and before and after
contracting the muscles of the part (e.g. clenching the hand), teach
the enormous importance of movement in maintaining the circula-
tion of the blood." Muscular exercise, by increasing the combustion
of food stuffs, and by _ ————E
furthering the circula- — _— 4
tion of the blood, and |
so elimination of tissue
waste, is the greatest
source of vigorous bodily
and mental health.
Standing erect and
with a leg relaxed the Nw
arterial and venous pres- Fic. 17. rea pressure recorded in carotid
sures in this leg become 2nd in femoral artery, each artery in turn being

5 placed in the axis of rotation of the animal holder.
higher than those inthe 4, horizontal ; F, D, vertical feet-down posture.

arm by the column of The difference between the pressures in this posture
was equal to the column of blood separating the

blood separating the two two arteries. Note increased action of respiratory
points of measurement. PU)

In students hanging head dowhwards by their feet, M. Flack and
the writer found the arterial pressure in the arm little altered from
the normal taken in the horizontal posture. Thus—horizontal,
brachial 126, post-tibial artery 126; standing, 140 and 204; head
down, 116 and 42. The pressure in the circle of Willis was about
20 mm. less than in the brachial in the standing, and about
10 mm. more in the head-down posture. Now the column of
blood above the point of observation is then in the six foot man
almost equal to the normal arterial pressure taken in the hori-
zontal position. The heart by lessened output and the vaso-motor
mechanism by increased dilatation can compensate for this hydro-
static pressure, and it is clear that the heart and brain are so_pro-
tected from a greatly increased arterial pressure. In the standing

1 Butchers say it is easy to bleed all the tissues of an ox if it is pole-axed after
being driven off the road into the yard, but difficult if it has lain down for some
hours.

144 THE VASCULAR SYSTEM

posture the column of blood in the vessels of the limbs can be
broken up into segments by muscular action, and the blood per-
mitted to circulate by alternate and appropriate contraction and
relaxation of the muscles. A most important and hitherto almost
unexplored reflex mechanism is here engaged, a mechanism in
which the skeletal muscles and the muscular wall of the arteries
each take a part, and in which sensory “receptors” are engaged,
tuned in sensitivity to capillary blood pressure.

To sum up then, the function of the heart is to drive the blood
into the capillary bed, the function of the arterioles is to regulate
the distribution and switch the current on to one or other part
of the capillary bed and limit the pooling of the blood under the
stress of gravity; the function of the skeletal muscles and res-
piratory pump, aided by the valves in the veins, is to drive the
blood back from the capillary bed to the heart, to prevent hypo- -
static congestion, and to act as a pump to the vascular system
of no less importance than the heart. The respiratory pump even ~
may drive the blood through the right heart and lungs.

Tue ACTION OF THE RESPIRATORY PUMP

The writer’s argument that the circulation is largely maintained
by bodily movement and varies continuously with every change
of posture and muscular contraction, and is liable to an extent
which defies analysis in the living active animal, is borne out by
recent researches of T. Lewis on the effect of respiration on the
blood pressure of man.

To determine this on man the sphygmograph can be used, but it
must not be fixed by a band encircling the wrist, because this entails
a serious fallacy due to the swelling of the volume of the arm. A
sphygmograph applied with a band acts like a plethysmograph.
T. Lewis fixed the sphygmograph by a suspension method and con-
trolled the results with a sphygmomanometer. The effect of pure
intercostal or pure diaphragmatic breathing in a trained subject
he found to be as follows :—

Suspended Suspended

Inspiration. Inspiration. Expiration. Expiration.
Thoracic . - \ = + + ~
Abdominal... + - - +

AND BLOOD PRESSURE 145

If both abdomen and chest participate in the breathing, inter-
mediate results will be obtained,—one effect will counteract the
other; and if abdomen or chest do not participate to the same
relative extent during different instants of a particular act, com-
plex curves will result which are beyond analysis. When a patient
is asked to take a deep breath, the breathing is often disorderly

\ f\ 1)

J I
J L/ ay et a ys * fe pith) Jv MI YN IN WI ied nl

—

Insp.
—BPLine _

D cwesr

Fic. 18.—Influence of chest and abdominal breathing on the pulse (Lewis).

in character, starting perhaps as intercostal and finishing as
abdominal.

In man a deep intercostal respiration, if not prolonged, yields a
fall of pressure, and conversely a deep diaphragmatic inspiration
yields a rise. But as the normal respiratory curves of blood
pressure are of very complex origin, and the different factors in-
volved vary widely, it is not possible to state what the effeet on
blood pressure will be, unless the conditions and nature of the
respiratory act are known. The ordinary statement in the text-
books that inspiration raises and expiration lowers blood pressure
is altogether unjustified by the records. The pressure almost

K

blk 7

146 THE VASCULAR SYSTEM ;

always falls when the patient is told to take a deep breath, and
thus what has been termed the pulsus paradoxus and considered
of pathological import, turns out to be quite a normal event.

In animals, says Lewis, under deep anesthesia, the abdomen

plays no part in the production of respiratory curves. The in-
spiratory rise is due to the lessened pressure in the pericardium
and consequent increased filling of the heart. It is abolished by
allowing free access of atmospheric air to the pericardial sac. The
varying intra-pleural pressure affects intimately the filling of the
heart, while its influence on the resistance and capacity of the
pulmonary vascular area is a matter of assumption rather than of
experimental proof. We are at present, says Lewis, justified by
experiment in ascribing the inspiratory rise in animals on intercostal
breathing to the effect on the heart only.

Tigerstedt found that ligation of the vessels of the left lung, .

-out of thirty-one observations, produced in eighteen no noticeable

effect on the output per second of the heart. In eleven cases it
produced a decrease of 6 to 10 per cent., and in two cases a decrease
of 18 to 20 per cent. In twenty-three cases the arterial pressure
was unaltered by this operation, in seven it was decreased
6 to 10 per cent., and in one case over 10 per cent. Thus the
pulmonary circuit can be shut off to a very large extent—at least
in the animal with artificial respiration—and the remainder
suffice to deliver an unlessened quantity of blood to the heart.
Tigerstedt’s observations also show that the arterial pressure may
sometimes remain constant when the output of the heart varies
considerably ; the explanation of this is that the arterial system
contracts down on the blood that it contains.

In Valsalva’s experiment—a deep expiration with the mouth
and nose shut—the abdominal pressure rises very greatly, and
this is the chief cause of the rise of arterial pressure which then
occurs. If a stiff-walled rubber tube is used as a rectal sound,
and is connected to a manometer, an estimate of intra-abdominal
pressure may be obtained, and this can be compared with the
expiratory pressure obtained by expiring against a mercurial
manometer. In one case the rectal pressure rose to 94 mm. Hg,
and the tracheal pressure to 87 mm. Hg. The same conditions
occur in coughing.

In deep abdominal breathing the rectal pressure may rise to-

30 mm. Hg, and frequently shows a range of 20 mm. Hg, a fact

4 °

1
a ae a

AND BLOOD PRESSURE 147

which shows what an effect such deep breathing has both on the
return of venous blood and on the resistance in the splanchnic area.
The action of abdominal breathing on the return of venous blood
may be easily demonstrated by opening the thorax of a cat just
above the diaphragm, and cutting a hole in the vena cava inferior.
With each descent of the diaphragm the blood spurts out. The
muscles of the abdomen and the levator ani support the abdominal
pressure, and the avoidance of prolapse of the viscera depends on
the proper exercise of these muscles and on the presence of an
adequate amount of fat in the belly.

EFFect OF MENTAL WorkK AND EMOTION

In curarised animals excitation of the cortex cerebri in the
motor areas of the limbs and trunk muscles raises the arterial]

Fic. 19.—1, Volume of abdominal organs; 2, volume of arm ; 3, respiration ;
+, pleasant; ,-— unpleasant taste.

‘pressure, by causing contraction of the splanchnic area, and dilates
the blood vessels of the limbs. Dilatation of the splanchnic area

148 THE VASCULAR SYSTEM

similarly is accompanied by constriction of the vessels of the
limbs. The cortex discharges motor impulses and alters the
circulation in accordance with the needs of the moving parts.
E. Weber has recorded in man the volume of the arm by means
of a plethysmograph, and the volume of the abdominal organs by
a rectal sound with balloon attached to the end of it, the sound

¥ic. 20.—1, Volume of abdominal organs; 2, volume of arm; 3, respiration.

From — to +, suggestion to hypnotised subject of his execution.

being connected to a strong tambour. He also has repeated
Mosso’s experiment of placing a man in the horizontal posture on
a long balanced board and seeing whether the head or feet end
becomes heavier in different emotional states. Weber put the
abdomen mostly on the foot side of the axis, instead of on the
head side as Mosso, and balanced by weights on the head side. He
found that mental work and painful emotions determine blood
to the abdomen, while pleasurable ideas and those of active move-
ment send blood from the abdomen into the peripheral parts.

AND BLOOD PRESSURE 149

Pleasurable feelings are accompanied by relaxation of the muscles
of the limbs and dilatation of the vessels of the limbs—relaxation
in contrast to the strained taut condition of work. It is not the
brain, as Mosso supposed, but the belly within which the blood
collects during mental effort. The brain, limited in its expansion
by the rigid cranial wall, contains a quantity of blood which can
vary but little, except when the tissues of the brain actually lose
or gain water, and so shrink or swell. Rise of arterial pressure
produced by the contraction of the splanchnic area does not
expand the brain so much as increase the proportion of arterial
blood to venous blood within it and accelerate the velocity of
flow. In muscular exercise the limbs receive more and the venous

cistern in the abdomen contains less. The stagnation of the blood

in the abdominal veins and liver during mental work and the
sluggish circulation caused by the arm-chair posture must have a
direct bearing on the irritable dyspepsia of brain-workers. Was
not Thomas Carlyle cured of his by horse riding? Exercise
sweeps the body clean of unoxidised food stuffs by the swirling
current of blood and the greatly increased rate of metabolism.
The breathing volume of a boxer after a three minutes bout may
go up from the resting volume 9 to 40 litres per minute. How the
muscles must squeeze the blood in his organs and drive it to the
right heart !

THE FintRatTion HyPoruHEsis

In the explanation of physiological and pathological processes
capillary pressure has been since the teaching of Ludwig constantly
evolved as a deus ex machina for producing filtration. Thus the
glomerular capillaries have been generally supposed to filter water
and salts into the renal capsules under the pressure of the blood,
which is supposed to be higher than that of the urine in the renal
tubule. Similarly in dealing with the formation of lymph, filtra-

_ tion by capillary pressure is supposed to be an important factor,
% a school of physiologists of whom Starling and Cohnstein in

st have been chief exponents. Dropsy and cedema, such as
occur in cardiac incompetence, have been attributed to filtration
brought about by increased capillary pressure; an altered per-
meability of the capillaries being admitted as an accessory patho-

logical factor in the explanation of the fact that increased vascular

ae

150 THE VASCULAR SYSTEM

pressure does not per se produce cedema in the healthy tissues.
To show to what an extreme limit this view may be carried, the
following example may be cited. Asher, a chief opponent of the
mechanical theory of lymph formation, has sought to overthrow
it by a number of ingenious experiments, of which the following is
one. He injected into the vein of a dog a concentrated solution
of sugar, and immediately killed the animal. The lymph flow from
the thoracic duct was measured, and this, in spite of the animal
being dead, increased from 4 to 37 ¢.c. per 10 minutes. In this
case, says Asher, there can be no question of a filtration pressure
because the animal is dead and the circulation at an end.» In an
argument upholding the filtration hypothesis, Bainbridge suggests,
however, that the sugar, by raising the osmotic pressure of the
blood, drew water from the tissues into the blood, and thereby

increased the volume and the mean (residual) hydrostatic pressure —

in the vascular system. ‘‘ The capillary pressure after death will
therefore,” he says, ‘be unusually high, and there will be an
excessive transudation of lymph, so that on analysis, the
experiment is seen to support, rather than to oppose, Starling’s
views.”

Now to make the mechanical theory possible we must suppose
that the blood is driven through a system of rigid tubes with a
sieve-like structure. If water be driven under pressure through a
coil of hose which leaks, and the coil of hose be sunk in a tub of
water, then it is. true water will filter through and the tub will
overflow. But,in an organ of the body the conditions are quite
otherwise, and an effective filtration pressure cannot exist because,
as the writer has proved in the case of the brain, the blood in the
capillaries, the tissue cells and lymph are at one and the same
pressure, viz. the capillary-venous pressure.

Let us take the example of the salivary gland. Asher has
pointed out that while lymph flows in increased amount when the
gland is thrown into secretory activity, from an atropinised gland
no lymph flows when the chorda tympani is excited, although the
arteries dilate, and the capillary pressure is raised. Here is an
experiment, he says, which is against the filtration hypothesis,
for capillary pressure is raised and yet lymph does not flow. The
experiment may prove Asher’s chief contention, that it is functional
activity with the consequent production of metabolites of high
osmotic pressure which determines the flow of lymph, but is not

4
.
n

AND BLOOD PRESSURE 151

required to disprove the filtration hypothesis because the con-
ditions are the same both in the resting and the excited gland,
in as far as the whole of any lobule of the gland must be at the
same pressure, and therefore no filtration pressure exists in the
one state more than in the other.

_ The gland is composed of a connective tissue framework, hold-
ing together tubules full of secreting cells, whose protoplasm con-
tains some 80 per cent. of water, the tissue spaces surrounding
the tubules are full of lymph, the capillaries of blood, and the
tubules of saliva. The wet films of protoplasm which form the
walls of the tubules, the capillaries, and the lymphatics, may act
as colloidal surfaces separating fluids of different chemical con-
stitution, but cannot possibly act as rigid sieve-like structures.
There cannot be a difference of hydrostatic pressure on either side
of the films, as is required by the mechanical theory. Molecular
not molar forces are here at play. The salivary cells are endowed
by their colloidal structure with the power of linking up or setting
free crystalloids brought to them in solution, and are thus the seat
of the play of complex forces of surface and osmotic energy, and
at the same time are the seat of chemical reaction, selective in
_ character and depending on the ferments they contain—-the keys
which fit the locks of chemical constitution. These living cells
control the passage of fluid in one or other direction, and the
mystery of the secretory process requires the same solution as in
the case of the unicellular organism, and this solution at present
is just as far from attainment in the one case as in the other.

The comparative study of the structure of the nephridial
tissues shows how far away from the truth are the mechanical
theories of renal secretion which have held their ground in physio-
logical text-books for the last fifty years. The writer has con-
densed the following passages from the work of Dahlgren and
Kepner.

In the unicellular animals the excretory organ is formed by
contracting vacuoles which form channels leading from the endo-
plasm to the exterior of the cell. The fluid that the vacuoles
throw out by their rhythmic expansion and contraction is drained
from the cell and is charged with uric acid. The contractile
vacuoles of Paramecium are two in number and permanent
_ features of the cell. Their inner surface dips into the endoplasm
___ and their outer surface opens through the ectoplasm to the exterior.

152 THE VASCULAR SYSTEM

Into each contractile vacuole a radiating series of drainage channels
lead. The channels are filled as the contractile vacuole discharges
its contents. In the higher animals tissues, selected for the secre-
tion of urates, form the nephridia. In the lowest Metazoa, so far
as is known, any surface cells may take on nephridial functions. The
higher forms of nephridial tissues are usually mesodermal structures.
These tissues are always epithelial; one face of the epithelium is
directed towards the fluids from which waste products are being
taken, the other face forms the surface of a retaining or conducting
cavity. In the Ascidians the renal epitheliuin is a vestigial cuelomic
epithelium. Into this blind space waste products are excreted
and stored as solid particles. All other nephridial sacs or tubules
deliver the waste products to the exterior through nephridial pores
or ducts. In all the simpler forms where the nephridial tubules
have a small lumen, the latter is intracellular. In invertebrates
where the lumen becomes larger, and in all vertebrates it is inter-
cellular.

The fluids from which the waste products are taken may be
intercellular fluid, coelomic fluid or blood. Intercellular fluid and
ceelomic fluid when associated with nephridia bathe them on their
proximal surfaces. The blood supply is effected in two ways. In
a few types the nephridial tissues are merely bathed in the blood
(Insecta). Blood is usually supplied to the nephridial tissues
through the capillaries of a circulatory system. In the simplest
tissues there is but an ordinary supply. In the vertebrates there
is a general capillary supply as well as a terminal supply. The
terminal capillary structure is a more or less distorted plexus
which is supported upon a connective tissue framework at
definite terminal regions of the nephridial tissues, forming a
“ glomus.” \

We may rest assured that the nephridial tissues act in
much the same way in every class of animal, viz. form vacuoles
containing granules of excretory substances and expel the con-
tents of these into tubules, Examination of the kidneys of
hibernating and thirsting animals show evidence of secretory
granules and vacuoles forming in the resting kidney. These
disappear when diuresis is established. There is no question of
filtration pressure in the excreting vacuole of Parameecium, none
~ in the case of Insecta where the nephridia lie in a bath of blood,
and consideration of the structural conditions which pertain in

AND BLOOD PRESSURE 153

_ the mammalian kidney will show that there can be no question of
a capillary pressure which can produce filtration therein.

The formation of glands in the embryo displays the same pro-
gressive evolution from the simple to the complex state, as is
observed in ascending the animal scale. The most perfect and
complex glands of the higher animals resemble in embryo the
secretory organs of the lower animals. The arborescent ramifica-
tions of the blood vessels accompany the ducts in their develop-
ment, and in proportion as the development of a secreting plane
surface into a cecum and ramified ceca proceeds, the vascular
layer of the originally simple membrane spreads as a closely in-
vesting network around them. The ramified secreting tubes,
which, when the structure is simple as in Insecta and Crustacea
and in the pancreas of the rabbit, lie free freely and unconnectedly,
in proportion as their evolution is carried further acquire a common
covering or capsule; and thus a solid organ is produced. The
vascular conditions in the simple and the complex are the same.
No one would be rash enough to suggest that filtration of fluid
could occur from the capillaries of the rabbit’s pancreas through
the ramified tubules exposed ia the mesentery in a thin sheet.
The tubules and the capillaries here are obviously at one and the
same pressure, that of the abdominal cavity, alike squeezed. by
the respiratory muscles, and pulsed by the wave of blood which
distends the abdominal arteries at each cardiac systole. There
is barely a positive pressure in the capillaries, but this, aided by
the rhythmic squeeze of the respiratory muscles, is sufficient to
maintain the onward flow of blood. The gland cells when excited
at times secrete their juice at a positive pressure, which with the
help of the peristaltic wave of the muscular wall of the tubules
drives the fluid into the intestine. Similarly in the case of the
kidney, the blood in the capillary networks, the tissue lymph, and
the urine in the tubules are all at one and the same pressure—
the capillary-venous pressure. The whole kidney is expanded by
_ each arterial pulse, and drops of urine may be squeezed thereby
into the pelvis from the mouths of the tubules. The whole kidney
is rhythmically squeezed by the respiratory muscles. The tubules
are formed of watery cytoplasm, surrounded by lymph spaces full
of fluid, and networks of capillaries full of blood. There is nothing
of a rigid structure here, nothing of the nature of membranes which
can separate fluid at one pressure in one system of tubes from

154 THE VASCULAR SYSTEM

fluid at another pressure in another system. If the capillary-
venous pressure were higher than the pressure in the tubules, the
latter would be obliterated until the pressures became the same,
likewise if the pressure in the tubules were higher than that in
the veins. If the ureter be obstructed so that the pressure rises
within it to say 40 mm. Hg, the capillary-venous pressure and
tension of the whole kidney rises to this amount, and it takes a
pressure of 40 mm. Hg to drive water through a hollow needle
into the kidney substance. If the renal vein be obstructed till

the pressure in the renal venules rises to 40 mm. Hg, the same must .

hold good, and the pressure of the urine in the renal tubules be-
come the same. If the arterioles of the kidney be dilated the
whole organ swells in its capsule, and the tension of the whole
rises, the vascular system and the tubular system together ap-

proximating towards the mgid condition, but both at the same ©

pressure, viz. the capillary-venous pressure. Under these con-
ditions the velocity of blood flow is greatly increased, and if the
kidney be enclosed in plaster of Paris, so that it cannot expand,
it makes no jot of difference, because the arteries dilate at the
expense of the veins, which are narrowed until a rigid system with
a rigid flow is produced. When the blood reaches the glomerular
capillaries, three courses are open to the fluid part, the capillary
wall retaining the corpuscles. It may pass on by the efferent

venules or by the lymphatics, or into the capsular ends of the’

renal tubules. Which course it takes depends on the play of
such forces as surface tension, adsorption, and osmosis. Filtration
has nothing to do with it, for the fluid pressure must be the same
on either side of the wet films engaged, which are of a tenuity
comparable to that of the bubbles of a soap lather.

Confirmation of the above views may be drawn from the per-
fusion experiments carried out by Sollmann on excised kidneys
in spite of the fact that the flow he obtained from the ureter was
attributed by him to filtration. He perfused 1 per cent. salt
solution at arterial pressure through the renal artery, and collected
and measured the outflow both from the renal vein and the ureter.
He found the venous flow reached its maximum in fifteen minutes,
while the ureter flow continued to increase for one to two hours,
thus rising slowly to a maximum. As the ureter flow increased
the venous flow declined slowly, and then. the two flows ran a
parallel course. Subsequently undergoing minor oscillations—the

a ~

—— ———

AND BLOOD PRESSURE 155

venous flow increasing slightly, and the ureter flow decreasing
at first, and then increasing. On altering the arterial perfusion
pressure the venous flow and ureter flow, the volume of the kidney,
the maximal venous pressure and the maximal ureter pressure all
varied in the same sense, but the maximal venous and ureter
pressures were at a lower level than the injection pressure owing
to leakage through capsular collaterals. If the perfusion pressure
were made rhythmically intermittent the venous and ureter outflow
were increased. Obstruction of the renal vein caused swelling of
the kidney and almost complete cessation of the ureter flow. A
graduated increase in the venous pressure, produced by raising the
level of the venous outflow tube, diminished the venous and ureter
flow and expanded the kidney, especially when the pressure rose
above 40 to 60 mm. Hg. The venous and ureter outflow varied
with the molecular concentration of the perfusion fluid. Hyper-
tonic solutions caused lessened resistance in, and more flow from,
the tubules and vessels, and hypertonic solutions the opposite.
In volume a hypertonic solution produced at first a sharp fall,
followed by a rise to original level, while a hypotonic solution gave
a progressive diminution in renal volume. Many of these results
are difficult to explain, but none are in favour of filtration. Vernon
has shown that the fluid coming from the kidney under these
conditions does not correspond to that sent into the artery. The
kidney metabolism continues for days after death in a modified
form. At first we see the perfused fluid found its way through
the capillary-venous system, and only much more slowly made a
passage through the renal tubules. At the start the capillaries
were distended with the perfused fluid, the lumina of the capsules
almost obliterated; the surface tension of the capillaries there-
fore was high, that of the capsules low. The surface energy of
the latter therefore was high. It may have been these conditions
which led to the transference of the fluid from one side to the other

of the wet film formed by the capillary and capsular epithelial
_ cells. We may suppose with justice that the epithelium retains

the corpuscles and the native colloidal material of the blood. -We
know some colloids may pass. Sollmann found gum arabic, added
to the perfused fluid passed through, and egg albumen passes into
the urine of normal people if much be eaten. In the case of the
renal tubules at the time when the capillaries become distended

_ with fluid, the epithelium of the tubules contains stores of ex-

5 Sa ae
’

156 THE VASCULAR SYSTEM

cretory products, some in colloidal linkage, some as crystalloidal
substance. In these cells there comes about a complex play of the
forces of osmosis and surface tension. Supposing the epithelium
of the tubules swells owing to their surface energy being great in
comparison with the capillaries where the surface tension is great,
then the epithelium in its turn will have a higher surface tension
than the lumina of the tubules, and this surface energy will cause
the transference of liquid from vessel to tubule. We have in the
kidney a gelatinous foam-like structure, the meshes of the foam
containing fluid, and the meshes being formed of two sets of ramified
channels, the one set leading to the venous and the other to the
ureter outlet. Blood is driven. in pulses into the vascular mesh-
work. By such forces as adsorption and surface tension the
fluid part of the blood pervades the tubular meshwork, while the
living cells concentrate, and extrude vacuoles filled with, urinary
excretions. The mystery of the whole process is hidden from us, but
we may be sure that an excretory cell in a bath of collecting fluid
and provided with an excretory channel form the structural basis of
the mechanism, and that the mechanical filtration theories may be
relegated to the conceits of a science in its more primitive days.
It has always been assumed by those who maintain the de-
fence of the filtration theory that the capillary pressure must be
raised not only when the general venous and arterial pressure rise
together, but also when the general venous pressure is raised, so
long as there is.no fall of arterial pressure compensating for this
venous rise. No such assumption can be made in regard to a
rise of arterial pressure because of the unknown factor—the re-
sistance in the arterioles. Now the experiments of Martin Flack
and the writer made on the arterial venous and capillary pressure
of their own limbs show that the above assumptions are, at any
rate in the case of the limbs, not valid. The capillary system is
not filled to distension ; there is a large potential space which only
gradually fills when the venous return is impeded, and thus the
venous pressure—the veins being filled by broad paths of low
resistance—-may rise greatly while the capillary pressure in large
areas drained by these veins is scarcely altered. The gradual
filling of the capillary system, while producing distension of the |
. part, enormously increases the surface exposure of the blood fluid
and the surface tension of the \capillary films, and these are pro-
bably factors of the greatest importance in the formation of lymph,

AND BLOOD PRESSURE 157

another factor being the alteration of tissue metabolism produced
by the impeded blood flow with consequent want of oxygen, setting
free of crystalloids from colloidal combination, and increase of
waste products, leading to a rise of osmotic pressure and swelling
of the tissues.

- In the case of such an organ as the liver a great expansion
takes place when the outflow from the vena cava inferior is impeded,
or excess of blood or saline is injected intravenously. Here again
increase of surface exposure and stagnation of flow are the factors
at work which produce the greater outflow of lymph—not the
increased capillary pressure. That the capillary pressure is in-
creased in such capsulated organs as the kidney, salivary gland,

liver, and brain when the outflow of venous blood (or secretion)

is impeded is proved by the increased tension of the organ, but this
increase must be uniform throughout each lobule, if not through-
out the whole organ, and cannot act as a filtering agent.

THE RESIDUAL VASCULAR PRESSURE IN THE DEAD ANIMAL

The vascular system as a whole is not filled to distension.
There is in the dead animal no uniform positive mean pressure
throughout the vascular system. If there did exist in the system
such a positive ‘mean hydrostatic pressure ” when the heart is
arrested and the skeletal muscles are relaxed by death, it must be
produced by some secretory power of the vascular epithelium or
by the osmotic pressure of the blood. The blood must possess a
greater power of holding water than the tissues, and the wet film
of the capillary wall must be able to retain the water, so that the
whole system is filled to distension. The shrinkage of the face
in fainting, and how much more in death, shows the error of this
conception. After death there is a residual pressure in the aorta
owing to the resistance in the arterioles which contract and do
not allow the last of the blood to leak through into the capillary-
venous system. There is also 4 residual pressure in the vene cave
produced by the influence of gravity and the post-mortem con-
traction of the viscera which drives the blood from the capillary
areas into the vene cave. These residual pressures are, however,
unequal, and cannot be taken as representing a “ mean hydrostatic
pressure” of the whole system. Thus the writer found in a ©

_ morphinised dog :—

=

158 THE VASCULAR SYSTEM

Aorta. | Vena Cava.
Mm. Hg. Mm. Hg.
165 | 3 Normal,
30 | 14 Heart arrested by
| vagus.
and in a morphinised and curarised dog :—
= aa 7
Aorta. | Vena Cava. |
Mm. Hg. | Mm. Hg. ie
80 | 3 Normal.
| 14 | * 6 Heart arrested by
vagus.

In the uncurarised animal the convulsive movements of res-
piration by compressing the abdominal vessels raise the vena cava
and lessen the fall of aortic pressure.

_ Similarly in Cohnheim’s classical experiments, when he injected
oil into the pericardium to study the effect of impeding the filling
of the heart, there resulted no equality of residual pressures in the
aorta and vena cava. .

It has been supposed that a general constriction of the arterioles,
such as may be produced by the injection of adrenalin, would by
reducing the capacity of the vascular system raise the “ mean
hydrostatic pressure,” and therefore the capillary pressure. The
writer produced by injecting adrenalin a rise of arterial pressure
from 80 to 180 mm. Hg, and then arrested the circulation by
clamping the ascending aorta. The vena cava pressure fell to the
same residual pressure as when the aorta was clamped before the
injection of the adrenalin. A rise of pressure of 1500 mm. of blood
in the aorta may be accompanied only by a rise of 50 mm. in the
vene cave, and this small rise is due not to diminution of the total
capacity of the vascular system, but to a greater return to the
vene cave of blood squeezed from the splanchnic area and the
failure of the heart to empty itself in the face of the high resistance.

It has been supposed that the intravenous injection of physio-
logical saline, or the injection of concentrated sugar solution—this
produces hydremia by drawing water out of the tissues into the
blood—it has been supposed that either of these agents increases

AND BLOOD PRESSURE 159

_ the flow of lymph by adding to the total volume of fluid in the
- vascular system, and thus increasing the capillary pressure and
’ filtration through the capillary wall. Now in a case of poly-

cythwmia studied by the writer, the arterial, the venous, and the
capillary pressure in the arm, held at heart’s apex level, were the
same as in himself. There was not a sign of congestion, except a
redness of the hands and face and fulness of the veins, and not a
trace of cedema in this man. And yet he had a hemoglobin per
cent. of 155, 33 times the normal oxygen capacity, 12,000,000 red
corpuscles per c.mm. of blood, and a total blood volume 2} times
the normal as determined by A. 8. Boycott.

During the temporary arrest of the circulation in the dog the
writer has injected rapidly 30 c.c. and more of physiological saline
solution into the venz cave, and observed only a temporary and
slight rise of pressure in the ven cave during the injection and
no effect at all on the residual pressure in the arteries ; an experi-
ment which shows without question that there is no such thing as
a positive “mean hydrostatic pressure” in the vascular system,
and that the pressure can be raised in one part witbout influencing .
another, owing to the unfilled areas of capillaries, and the roomy
capacity of the veins.

Dog: Cannulex, in Aorta and Vena Cava Superior, connected with
Manometers filled with 1 per cent. Sodium Citrate Solution.

l
mime, Beta Aortic enya Vena Cara |
Mm. H,0. Mm. H,0. | |
317 | 114 89 Pulmonary artery
| occluded. wa
3°18-19 114 204 Convulsive respira-
tions.
3:30 70 64 Heart poisoned by |
chloroform |
} 832 70 127 100 cc. saline in- |
jected into femoral
| vein.
3°35 76 7
3°45. | 63 56

Tue Erect or Onsrructine THE Vena Cava
Some remarkable experiments by C. Bolton may be cited here

in connection with these experiments of the writer. Bolton

160 THE VASCULAR SYSTEM

studied the result of totally obstructing and of narrowing the
ven cave in order to arrive at the share in the production of
dropsy which increased capillary pressure had. He tried at first
to produce cardiac deficiency by constriction of the pericardium by
means of sutures, so as to prevent the proper diastolic expansion
of the heart, but gave up this line of work as he found it very
difficult to hit the right amount of constriction. The animals
either died or recovered without symptoms. To obstruct the
ven cave he made an incision one to two inches long parallel to
the ribs in the third right intercostal space for the superior, and
seventh space for the inferior cava. Artificial respiration was put
on, the ribs drawn apart by retractors and the lung held aside by a
spatula, and incomplete obstruction set up by encircling the vein
with a short piece of soft rubber catheter of appropriate diameter.

The thorax was then closed, after squeezing out the air, and the:
animal allowed to recover. The venous pressures were measured
in some of the animals after varying degrees of constriction had
been established, the measurements being taken in the external
iliac; at the lower end of the femoral above the ankle; in the
splenic branch of the portal; and in the post-auricular branch of
the external jugular. Complete occlusion of the superior cava
caused the death of the animal in one to six days. There was
caused considerable cedema of the mediastinum and exudation of
venous fluid in the pericardial and pleural sacs. The animal
refused food, wasted, and passed less urine. When the obstruction
was made above the azygos vein, one anima! survived, efficient
anastomoses becoming established by way of the internal mammary,
azygos, veins of diaphragm and comes nervi phrenici. There was
cedema and fluid in the pleura and pericardium until these
anastomoses were established properly. Another animal died
eighteen days after operation, and 145 c.c. of fluid were found in
the right and 125 c.c. in the left pleural cavity. In the cases of
partial obstruction Bolton found constriction to three-fifths of the
normal size produces cedema and hydrothorax.

Such obs*zuction only raises the venous pressure in the external
jugular by 20 to 40 mm. of blood, and quite temporarily. Com-
plete obstruction altered the arterial pressure very slightly and
raised the pressure in the external jugular by 130 mm. of blood,
but within an hour the pressure was normal again. The cedema
and dropsy were produced next day long after the pressure had

AND BLOOD PRESSURE 161

become normal again. Complete obstruction of the inferior cava
caused death in a few hours (as was determined by R. Lower in
the days of Charles II.). The arterial pressure at once fell to
30 to 40 mm. Hg, and the venous pressure in the external iliac
tose by 100 mm. of blood or more, but within an hour fell back to
its old level.

Partial constriction to more than three-fifths caused death.
The diameter of the vena cava is about 5 mm., and on constriction
to 3 mm. the animal survived, while on 2 to 24 mm. it might or
might not die. The arterial pressure fell about 20 mm. Hg when
the constriction was to 3 mm., and the pressure in the external
iliac vein rose 20 to 30 mm. of blood, but this rise was quite tem-
porary. Ascites resulted until proper anastomoses were established
by way of the veins of the abdominal wall; but the first signs of
ascites occurred long after the venous pressure had returned to
normal. Constriction of the portal vein from its normal diameter
4 mm. to 14 mm. gave the same results as constriction of the
vena cava inferior. Constriction of both cave to 3 mm. produced
dropsy of the pleure and peritoneum just as in a case of uncom-
pensated heart disease.

Finally Bolton observed that 130 c.c. physiological saline (an
amount equal to from two-thirds to the whole blood quantum)
might be slowly injected in the course of one and a half hours, the
blood pressures remaining normal, and some ascites being produced
meanwhile.

In the experiments on the effect of complete obstruction of the
inferior vena cava he records that while the pressure in the external
iliac vein rose by 100 mm. of blood or more, that in the femoral
vein above the ankle only rose by some 60 mm. _ The writer
attributes this to the low pressure in the arteries, the derivation
of the arterial blood through the lower resistance channels—the ab-
dominal vessels—and consequent slow filling of the veins of the legs.

Bolton’s observations show that the ascites and cedema occur
when the general venous and arterial pressures are normal. They
must be ascribed, therefore, to altered tissue metabolism, greater
filling of and stasis in capillary areas, and consequent change in
the conditions of surface and osmotic energy.!

1 The work of B. Moore and his co-workers has shown how the osmotic pressure
____ of the complex of colloids and crystalloids which forms the serum or tissue proteid
is altered by slight changes in alkalinity, &c. See Bio-Chemical Journal, vol. iii.
| - P- = 1908,
L

162 THE VASCULAR SYSTEM

The mechanical theory as to the causation of cardiac dropsy
has been summed up by Bainbridge as follows :—

“First, in an uncompensated heart, there is a fall of arterial
pressure, and a rise of venous pressures near the heart. There is
also a fall of capillary pressure, in consequence of the fall of arterial
pressure, in the kidneys, intestines, and peripheral parts of the
body. The fall of capillary pressure lessens filtration, and for a
time upsets the balance between filtration and absorption ; con-
sequently an excess of fluid is absorbed by the blood vessels from
the intestines and peripheral tissues.

“Secondly, this continued absorption associated with the
diminished urinary secretion, leads to hydremic plethora, and
increases the mean systemic pressure.

‘“‘ Thirdly, this hydreemic plethora raises the capillary pressure

all over the body, and promotes increased filtration, the more so

because the venous state of the blood damages the capillaries,
and increases their permeability. A further subsidiary factor is
the obstruction to the entrance of lymph into the great veins at
the thoracic duct owing to the excessive venous pressure.”

The writer controverts these views in each particular—the
arterial pressure is not altered in uncompensated cases of heart
disease unless death is imminent; neither is the venous pressure
altered, nor the capillary pressure.

Neither hydremic nor blood plethora raises the arterial venous
or capillary pressures excepting during the period of intra-venous
injection. Even if the capillary pressure were raised it would not
cause filtration because the blood in the capillaries and the tissue
lymph in any organ are and must be at one and the same hydro-
static pressure.

THE EFrFrect OF OBSTRUCTING THE BLOOD VESSELS

While cessation of the blood flow in the “ higher level ” centres
of the brain abolishes consciousness in a second or two, perma-
nent recovery from a complete anemia may occur which has lasted
some minutes, at the outside twenty minutes (Stewart and Guthrie).
The heart quickly stops beating when the coronary arteries are
closed, but can be recovered by transfusion hours after. Muscle

1 A temporary recovery may occur after sixty minutes, Guthrie transplanted

the head of a dog, and obtained reflex movements of the eyes, &c. ‘The circulation
in the brain had been interrupted twenty-nine minutes.

AND BLOOD PRESSURE 163

can stand a much longer anemia than the heart and viscera, and
connected tissue and epithelia still longer. After the obstruction of
arteries, beyond the possibility of an efficient current being set up
by way of anastomotic pathways, the capillary-venous area of the
| part affected fills by the slow inflow from surrounding areas, the
plasma passes out owing to the altered osmotic conditions, and
the red corpuscles heap together. Such congestion is seen in the
tongue of the curarised frog after tying the artery on either side
of the under surface. If the root of the ear of a rabbit be confined
by a ligature for eight to ten hours, and the string be loosened,
the ear swells and becomes very red, and the tissue lymph and
white corpuscles increase in the tissue spaces. After ligation for
twenty-four hours, small hemorrhages occur, the permeability of
the capillaries being then seriously altered.

The effect of back congestion has been studied in the frog’s
tongue after tying the veins which on either side carry the blood
from the tongue to the larger veins in the floor of the mouth
(Cohnheim, Thoma). The. congestion can be observed micro-
scopically as it spreads backwards. The veins and capillaries
widen in the tongue, but scarcely so in the web of the foot where the
surrounding tissue is inextensile. As the plasma escapes into the
tissue spaces, the capillaries and veins become choked with red
corpuscles. If a cannula is placed in the lymphatics on the outer
side of the leg of a dog, and a hgature is drawn round the thigh so
as to obstruct the veins, the lymph—before scarcely moving—
begins to flow, and the foot may swell, gradually becoming
cedematous. Division of the vaso-constrictor nerves increases the
effect. This is well seen on obstructing the veins of the root of the
rabbit’s ear and dividing the cervical sympathetic nerve.

If the veins of the dog’s leg are entirely obstructed by injecting
plaster of Paris into the vein on the dorsum of the foot—confining
the thigh by a ligature during the injection—the leg next day is
become cylindrical with cedema. The kidney swells after ligation
of the renal vein to double or treble the size, and bloody extra-
vasations appear in its substance. In the frog’s tongue the red
cells may be seen escaping through bulgings which appear in the
capillaries and small veins, that is when the venous obstruction
is complete. In all these cases increased capillary pressure is not

_ the prime cause of the phenomena. They result from stagnation,
altered metabolism, and altered osmotic energy dnd surface energy

164 THE VASCULAR SYSTEM

of the capillary cells and tissues. The appearance of a part in a
state of passive hyperemia is livid and bluish, swollen, pitted by
pressure ; its temperature is lowered. The degree of swelling
depends on the relative in and out flow of blood. It is little
in hypostatic congestion because of the feeble arterial supply.
Whether the tissues live or die depends on the maintenance of
some flow by collateral paths.

When a vein is slowly closed by a thrombus, collateral path-
ways have time to enlarge. “Thrombosis of the common iliac
vein or vena cava inferior produces oedema of the lower limbs
and compensatory enlargement of the cutaneous vessels of the
legs and abdominal wall. Thrombosis of the subclavian vein can
be compensated by collateral paths through the internal mammary
and intercostal veins, and even thrombosis of the innominate vein
fails to produce cedema if the laryngeal descending veins remain
open.” The effects depend on the rapidity with which the throm-
bosis takes place, 7.e. on the relative damage of the tissues by
deficient flow. If the inferior cava is thrombosed rapidly, general
oedema occurs below the level, and blood and albumen appear in
the urine if the renal veins are involved. Closure of the portal
vein by a tumour or of its branches by cirrhosis of the liver, leads
to congestion of the intestines, enlargement of the spleen, and
ascites. Here again the results are due entirely to deficient flow
and altered constitution of blood and tissue cells. The cranial
sinuses are liable to thrombosis. They are wide, of irregular
lumen, with Pacchionian granulations dipping into them, and in
some cases bands crossing them. The current is forwarded by
respiration but cannot be influenced directly by muscular con-
tractions. Hence thrombosis occurs in marasmic states, with
feeble respiration and deficient cardiac power. Sudden blockage
of an artery by ligature or embolus is of little effect so long as there
are adequate collateral anastomotic paths. These rapidly dilate,
and while the blocked artery shrinks up the anastomotic capillary
paths, where the flow is increased, develop the structure of arteries.
Retinal, coronary, renal, splenic, and cerebral arteries beyond the
circle of Willis behave as terminal arteries. Closure of these and
of the superior mesenteric artery in spite of its collateral paths, —
leads to stasis and necrosis. It seems to be possible for an embolus
to be driven by the respiratory and muscular movements in a
retrograde fashion down the large veins by coughing or expiratory

AND BLOOD PRESSURE 165

effort, for after the injection of emulsions of white sand into the
jugular or femoral vein, grains have been found in the veins of
the face, liver, kidney, as well as in the venew cave. Thus the old
Galenical doctrine that the blood is driven down the veins from the
liver to the body has a grain of truth in it.

PLETHORA

When freshly defibrinated dog’s blood, warmed to body
temperature, is injected into a dog by way of the jugular vein, the
arterial pressure may rise with each injection some 20 to 30 mm. Hg,
but quickly returns to its old level. After blood to the extent of

3 to 4 per cent. of the body weight has been injected the arterial
pressure may reach the height of 170 to 180 mm. Hg, but much
beyond this it cannot be driven. If the transfusion be continued
until more than 10 to 12 per cent. of the body weight has been
introduced—t.e. more than twice the normal blood quantum—
significant upward and downward variations of pressure occur,
which presage cardiac failure. All the animals die in the course
of a day or so who have received over 10 to 12 per cent. of their
body weight.

During each period of injection the heart being better filled
responds with an ampler output and raises the arterial pressure.
The pressure returns to its old level so soon as the injected blood is
swallowed up by the capillary-venous reservoirs.

Finally, when so much blood has been introduced that the
venze cave and liver have become distended, the heart becomes
over-loaded, and having to perform its systole in a dilated state
and owing to its greater output against an increased resistance,
begins to fail. The share of the vaso-motor system in the restitu-
tion of the pressure in the early stages of the experiment is made
manifest by dividing beforehand the spinal cord in the lower
cervical region. The low arterial pressure, which obtains after
such a lesion, is driven up by each injection until the normal arterial
pressure is reached and restitution of pressure between the injec-
tions then occurs. The falling back of the pressure after that point
has been reached is due to the escape of the blood from the arteries
into the capacious capillary-venous areas.

It is in the small veins and capillaries and particularly in the

___ abdominal organs that the excess of blood lodges. The pressure

166 THE VASCULAR SYSTEM

in the vene cave rises during each injection but sinks again owing
to the extensibility and large potential capacity of the capillary-
venous system. The liver holds a great deal and becomes large
and firm to the touch, and when excised a great quantity of blood
streams from it. The large abdominal veins and liver by receiving
most of the blood injected protect the heart from over-distension,
but if the transfusion into the jugular vein be made too rapidly,
no time is given for the filling out of the liver and other capillary-
venous reservoirs, and the heart becomes over-loaded and fails.

Plethysmographic records of the heart showed Johansson and
Tigerstedt that with a sufficiently slow transfusion there is an
increase in the systolic output and no passive congestion of the
heart occurs. With a more rapid rate of transfusion the heart
fails to empty itself and expels a smaller amount of blood than |
before. Hence the constancy of the arterial pressure during
transfusion is to be ascribed largely to the heart’s action.

Rabbit: period of transfusion of 20 per cent. of blood
quantum marked by the vertical lines :—

Output measured by Stromihr introduced into Ascending Aorta

Arterial pressure . 78 | 88 99 97/114 131 134 133 140
Output of heart per 18 | 32 53 39/| 31 33 32 38 36
minute per kgm.
of body weight
144 147 148 146 148 147 148 149 147
36 3606 «633806 (360 33244 45 OSC

145 131 119 112 107 104 101 99 94 90
66 66 66 61 59 59 59 54 50 51

The following shows the effect of a larger rapid injection =
50 per cent. of the blood quantum :—

Arterial pressure . 78 | 89 120 130 144 158 160|151 146 136

Minute volume . 33 | 49 80 71 51 35 32] 31 32 33
131

and so on to >, and then to | = the output rising as the arterial

pressure fell and the heart recovered as the blood fluid found room
in the capillary-venous system and tissue spaces.

After an injection of 69 per cent. of the normal blood quantum _

in the period of fourteen minutes the heart worked well at first,
and the arterial pressure rose from 50 to 125 mm. Hg. After
twenty minutes the heart failed, the minute volume sank to half

AND BLOOD PRESSURE 167

its original value, and the pressure fell from 117 to 37 mm. Hg.
On, bleeding the rabbit 12 c.c. and then 20 c.c., and then again
another undetermined amount, the pressure rose and reached 40
mm. Hg some twenty minutes after the first signs of cardiac failure.
At the end of another twenty minutes it had risen to 79 to 86

It is possible that the cardiac failure may be due in part to
other causes than the mere mechanical overloading of the heart.
Some experiments made by Bier seem to show that defibrinated
blood has a toxic influence, for he found that if he transfused the
excised limb of a pig with pig’s blood, defibrinated and oxygenated,
at arterial pressure, an active hyperemia ensued at first, and the
- blood flowed from the veins in a full stream. Soon, however, the
outflow diminished and became very small, and the limb turned
deep blue in colour. Arterial blood transfused directly into the
limb from another pig had no such effect ; the limb at each trans-
fusion became hyperemic for a time and then returned to its
natural colour.

Worm-Miiller observed that bleeding an animal, to the extent
only of that amount of blood which had been injected, killed it,
if the transfusion had been a large one. The excess of blood fluid
in part pooled in the expanded capillary-venous system and in
the tissue spaces, in part excreted, could not be drawn on quickly
enough to maintain an adequate supply to the heart.

Much has been made of the increased resistance which is said
to occur in plethora owing to transudation and excretion of the
blood fluid and the concentration of the corpuscles. To the
greater viscosity so produced the overstrain and failure of the
heart has been attributed. The researches on surviving organs
show on the whole the same proportion between viscosity and
flow, as in a glass viscometer. If the viscosity is increased
50 per cent. the flow will be about 50 per cent. slower. Such
an alteration of viscosity is, however, of little significance in the
vascular system, for a slight excitation of the vaso-motor nerves
can alter the flow 100 per cent. or more. In the chewing muscles
of the horse the flow may increase four times or more during work
owing to vaso-dilatation and the furthering of the blood flow by
the alternate relaxation and contraction of the muscles. A drug
such as Yohinbim may in the first stage of its action lessen flow
_ 50 per cent. and pressure 18 per cent., and subsequently increase

168 THE VASCULAR SYSTEM

flow 250 per cent. and pressure 11] per cent., so great is the
effect of vaso-dilatation coupled with increased cardiac efficiency
(Brodie and Miiller).

In polycythemia, where the blood is more than doubled in
quantity and the number of corpuscles twelve million instead of
five, there are no signs of high pressure, hypertrophy of heart, &c.
The heart continues to circulate about the normal amount, and
the excess is stored away in the peripheral capillary-venous areas.
Increased viscosity is compensated for easily by dilatation of the
arterioles. The toxic conditions which arise in cases of poly-
cythemia are probably due in part to the long time much of the
blood must take to complete the circulation. Thrombosis also
results in the cerebral veins. The viscosity of the blood may be
increased nearly 100 per cent. by stasis—produced by confining it
within a limb for twenty minutes by means of a rubber bandage.
The increase is due to the passage of blood fluid into the tissues.
In cholera and polycythemia the viscosity co-efficient has been
observed to be as high as 20 in place of 4:8, the normal worth.
A current of carbonic acid led through the blood, it is said, in-
creases the viscosity 50 per cent. The maximal effect of hard
work or Turkish baths and sweating is an increase of 20 to 30
per cent. .

HyDR2MIA

Extraordinary amounts of physiological saline can be infused
without harm—up to 60 to 70 per cent. of the body weight! No
bad after effects follow the injection of threefold the fatal amount
of blood. The arterial pressure is not notably altered, and the
vena cava pressure, while rising by some 200 mm. of blood during
the injection, soon returns again to the old level. The velocity of
flow in the capillaries is greatly increased, as may be seen in the
frog’s web, owing to the dilated arterioles and lessened viscosity.
The output of the heart is immediately increased, and the heart
shows no sign of failure. Thus Tigerstedt found on injecting into
the rabbit 25 c.c. Ringer sol. (period of injection marked by
vertical lines) :—

Arterial pressure . 90| 96 99 97 | 8% 92 89
Minute volume perkg. 51 | 64 78 100 | 95 122 122

falling in a few minutes to .

AND BLOOD PRESSURE 169

The greater part of the water passes rapidly out of the vascular
system, the glands all actively secrete, watery urine is passed, the
saliva drips, the guts become filled with watery solutions, the
lymph flows in a continuous stream from the abdominal organs
but not from the lymphatics of the limbs. After death the sub-
cutaneous and intermuscular cellular tissues and the central nervous
system and usually the thoracic organs are as dry as normal, while
the abdominal organs are markedly oedematous and the peritoneal
cavity contains fluid. Scalding, toxic agents, temporary anemia,
by altering the vascular tone and conditions of surface and osmotic
energy of a limb, render it cedematous when the state of hydraemia
is produced. An hydremia maintained by daily injection has the
same effect, so that ligation of the femoral vein, which normally
does not produce cedema in the animal, in such case does.

A number of toxic substances are known which have the effect
of so altering the relations of osmotic and surface energy that
hydremia causes cedema in the limbs. The cedema which occurs
in renal disease is probably to be explained on these lines. The
factors to consider are—a scanty output of urine, particularly of
solid constituents, retention of salts and other waste products,
with consequent alteration in osmotic conditions leading to the
passage of fluid into the tissue spaces; excessive metabolism of
the muscles resulting from the defect of renal functions ; an effort
on the part of the tissues to-excrete into the body spaces waste
substances (this is the normal process in the ascidian) when the
nephridial tissue fails. Mellanby maintains that the creatin
found in the muscles is a waste product stored therein with
advancing life.

The injection into the blood of a concentrated solution of a
crystalloid such as sugar produces hydremia. Water is drawn
from the tissue space into the blood vessels and to such an extent
that the injection of 45 c.c. of 75 per cent. solution of dextrose may
temporarily double or treble the volume of blood fluid in a dog,
as measured by the alteration in number of red cells (Starling).
The lymph flow which is greatly increased in quantity is ascribed
to increased capillary pressure and filtration. In confirmation of
this view Starling found that if he drew off an adequate amount of

1 If a shrunken tissue cell border on a distended capillary, the surface tension of

the capillary will be high and its energy low ; while the surface tension of the tissue
_ ell will be low and its energy high—the one strives to shrink, the other to swell,

=

170 THE VASCULAR SYSTEM

blood beforehand so as to compensate for the incoming of the
tissue fluid, no noteworthy increase in the lymph flow occurred.
Objections to the filtration hypothesis have already been fully
stated ; it remains to suggest another explanation for Starling’s
results. The following hypothesis, for the present, may be found
adequate.

The injection of the sugar increases the osmotic energy of the
blood above that of the tissues, and draws water into the vascular
system. The capillaries are better filled and the surface energy
of the tissue spaces is increased in proportion as the surface tension
is increased in the capillaries. Sugar passes through the permeable
film formed by the capillary wall into the tissue spaces and cells,
and thus the osmotic pressure of the blood falls. Surface energy
then gets the upper hand and water passes from the distended

capillaries into the tissue spaces. This occurs particularly in the

highly vascularised abdominal organs where the flow of lymph is
furthered by the respiratory pump.

HYPERAMIA

The blood supply of each organ is in relation to its functional
activity, and thus while half of the whole blood quantum is esti-
mated to be in the viscera, and the blood they contain may be
equal to one-fifth of their weight, that within the locomotor organs
in the resting state of the animal is said to be not more than
2 to 3 per cent. of their weight. The capillaries of the skin are
normally far from filled. The effect of an irritant on the vessels
of the skin or conjunctive and on the mucous membrane of the
lip demonstrates the striking difference in the capillary supply.
Hypereemia may be active and arterial in origin, or passive and
due to venous congestion. Active hyperemia may be caused by
increased resistance in other vascular fields—the arterial supply
to the brain is increased by constriction of the splanchnic area—
or it may result from vaso-dilatation, and this in its turn may be
produced by the vaso-motor nerves, or by physical or chemical
agents acting locally, e.g. effect of heat and cupping on the skin,
pilocarpine on the salivary glands and diuretics on the kidneys.
It is suggested that the products of secretion cause vaso-dilatation
in the salivary gland when the chorda is excited, saad as excretory
products dilate the renal vessel.

AND BLOOD PRESSURE 171

The arterial wall responds to increased tension by contraction,

and to diminished tension by expansion, and thus tends auto-

matically to compensate variations in aortic pressure and keep

. the blood flow constant. That the vaso-motor centres have no
share in this is shown by an experiment of Bier. He amputated
the limb of a pig, leaving it connected with the body by an arterial
cannula only, and found that an active hyperemia followed a
temporary arrest of the arterial supply.

The following is one of the most interesting experiments of Bier.
He produced venous congestion of the arm by means of a bandage,
then tightened the bandage so as to obliterate the artery, and
lastly after five minutes loosened the bandage. The venous con-

gestion was at once replaced by an active arterial hyperemia.
He concludes then while arrest of the arterial flow is followed by
active hyperemia, venosity of the blood causes arterial constriction.
To confirm this conclusion Bier rendered bloodless the limb of a
pig for ten minutes by means of an Esmarch bandage, and then
loosened it. The limb responded by the usual active hyperemia.
He next closed the windpipe of the animal, and noted that the
limb first became blue and then paled. On opening the windpipe
the active hyperemia returned, to be abolished once more on
closing it.

One more example of the influence of chemical state of the
blood on the circulation is the following. Bier exposed the rabbit’s
intestine in a bath of warm salt solution, and stopped the blood
supply to two loops of it, one of which was empty and the other
filled with milk at body temperature. On lessening the ligatures,
the one filled with milk responded by an active hyperemia, the
other not. Bier says the intestine of a fasting animal does not

become hyperemic after a temporary anwmia, while that of a fed
' one does, an observation which is of some interest to the surgeon.
The stomach of the rabbit does not give the hyperemic reaction
while that of the dog does, so that ligation of the chief arterial
supply of the stomach causes necrosis in the one and not in the
other animal. Man is like the rabbit in this respect. While
obliteration of the mesenteric arteries for a length of only 3 cm.
produces necrosis in the small intestine, 10 cm. is the minimum in
the colon of the rabbit.

Bier points out that every organ in functional activity is in a
____ state of active hyperemia, so too where tissue growth is great as

172 THE VASCULAR SYSTEM

in the regeneration of feathers after moult. The procreative and
reproductive functions too are accompanied by active hyperemia.
Hypereemia is the natural reaction of the tissues to injury, foreign
material and bacterial invasion, and this hyperemia is not to
be combated, but regarded as the natural healing agent. Anti-
phlogistic treatment, says Bier, may relieve the pain, but it retards
the healing process, and may render it less complete. The treat-
ment of Bier and of A. Wright is to promote the flow of plasma
into the infected or inflamed tissues. Venous congestion or cupping
are the methods employed by Bier.

The knife of the surgeon employed in the opening of ab-
scesses, &c., has the same influence in relieving tension and allow-
ing the free transudation of plasma. Wright employs sodium
citrate solutions as a drug or locally as an irrigant to lessen coagu-.
lability and thus increase the permeation of the infected part.
Chronic disease is chronic because the bacterial excitant does not
provoke an active hyperemia; make this appear and healing
follows. Animals infected with anthrax and streptococci have been
protected by the induction of venous congestion in the infected
part owing to the intensified “antitropic ” action of the plasma.
The defence lies in the plasma, and hence while blood infection is
rare local infection is of every-day occurrence. The plasma is
turned on to the infected local area in full stream, and if nature
fails to do this, the surgeon must aid the transudation. Salt
tubbed into wounds of slaves after whipping by osmotic force has
this effect, while hot fomentations produce hyperemia and soften
the skin and so allow more transudation.

Resorption is favoured by the hyperemia which follows venous
congestion, especially if massage be employed. Potassium ferro-
cyanide solution, introduced into a joint, appears thirty minutes
later in the urine. When hyperemia of that joint is induced the
salt appears in the urine in six to ten minutes. Lactose is a good
test substance to inject because its presence in the urine can be
detected by the polarimeter. The resorption of this is doubled or
more in rate by exposure of the animal to hot air and made very
slow by packing the limb in ice. When two limbs of an animal,
with the bones fractured, are splinted, and “one limb surrounded —
with an air bath at 38° C. and the other at 10° C., a callus forms
in six to seven days in the limb which is kept warm, while the re- —
generative process has just begun in the other. Hence the curative

AND BLOOD PRESSURE 173

effect of poultices and stimulating solutions lies in the hyperemia
and greater flow of plasma which they produce. The old ideas
underlying the words “ derivants” and “ revulsants ” are entirely
wrong. Mustard poultices and turpentine stoups do not draw
the blood from the deeper diseased parts into the superficial,
but produce hyperemia of both. The abdominal organs are ren-
dered hyperemic by exposing the abdomen to a hot air bath.
The intra-pleural temperature may be raised slightly (owing to
hyperemia) by applying an irritant to the skin of the chest, and
may be raised several degrees by applying hot poultices. The
greater warmth of the part not only induces hyperemia but in-
creases phagocytic and other actions. Herein we find the explana-

tion of the success of these old-fashioned remedies in the treatment
of fevers and inflammation. Bleeding likewise may have been
effectual by drawing tissue lymph into the blood and so increasing
the stock of bactericidal and opsonic substances. It is unlikely
that our forefathers bled fever-patients for nothing excepting
the fee.

SHocK AND COLLAPSE

When a large hutch rabbit is held for a few minutes in the
vertical position with its limbs stretched out and head uppermost,
it may become unconscious and die from cerebral anemia. The
blood collects in the large flaecid abdomen, the animal not being
able to return it to the heart by changing its posture. It struggles
to maintain a circulation—cerebral anemia excites convulsions
which squeeze the blood from the limbs, &c., into the heart—but the
difficulty in face of the circulation is too great and the animal dies.
A wild rabbit with taut abdomen is not affected in this way, neither
is a cat or dog, but a goat is with its capacious belly. The wild
rabbit can, however, be brought into like state by a dose of chloral,
and so can the dog by chloroform poisoning or by bleeding. The
emotional fainting of a man is.due to the inhibition of the nervous
system—a neutralisation of all other afferent stimuli by one all-
powerful one—the consequent sudden relaxation of muscular tone,
collapse of the body and non-return of venous blood to the heart.
The horizontal postute or compression of the abdomen immediately
restores from syncope the rabbit or the man. The condition of
shock which results from division of the spinal cord in the lower
cervical region is recovered from and cannot be renewed by

174 THE VASCULAR SYSTEM

a subsequent section or total destruction of the spinal cord
(Sherrington). It is caused by the sudden interruption of the
nervous tonic influence which proceeds from the brain to the
muscular system. The incessant inflow of visual and labyrinthine
impulses no doubt maintain this tone ; just as the wires of a piano-

tet tat ay tate Et tye yy Yt yy ty testi

ah
“ mV!) yin
; Singita, ded ater dsb Mii bphttots
if prep MRM HR iit aR MIAN

x

s
5
%

Hg

Fic. 21.—Carotid and superior vena cava pressures’ of dog. FD, animal
turned into the vertical feet-down posture with the cannule in the axis of
rotation. The arterial pressure fell in fifty minutes from 110 to 42 mm. Hg.
From C to EX the animal was immersed in a bath which was deepened to the
chin at D. Note the increased effect of respiration on the venous pressure
after FD, and again after the bath. Note the fall of pressures at FD and
the compensatory rise in arterial pressure, which gradually weakens.

forte are ceaselessly kept humming by the noise of the world, so
is the neuro-muscular system. Shock may be caused in man by
any severe injury, and is generally attributed to paralysis of the
vaso-motor centre. The centre is said to be exhausted by the
violence of the sensory stimulation (Crile). Porter objects to this
view, and says it is disproved by the fact that the centre responds
to excitation of a sensory nerve in the usual way, and in an animal

*

AND BLOOD PRESSURE 175

in a condition of shock from injury raises the arterial pressure from
its low level by an amount which is no less than in a normal animal.
The centre, he says, is able to act quite efficiently. The fault
may lie, however, in the sensory synapses. The centre fails to
be excited by the usual weak excitation streaming into it, or the
usual effect may be reversed—pressor turned into depressor reflexes,
and so the arterial tone flags.

sayliss has brought forward evidence that there exists a

Fic. 22.—Inhibition of constrictors in Lovén reflex. Upper curves, volume of
hind-limb ; lower curves, arterial pressure. First excitation, median nerve ; second,
sixth lumbar posterior root (Bayliss).

reciprocal innervation in the case of vaso-motor reflexes as in
those affecting skeletal muscle. Under normal conditions the
arterioles are in a state of moderate contraction or tone, which
may continue even when the vessels are separated from connection
with the nervous system. Such tone is a normal property of smooth
muscle, and in the case of the vessels it seems to be kept up by
the contractile reaction of the arterial wall to the distending force
of the pulse, as well as, it is thought, by the internal secretion of
the adrenal glands acting on the sympathetic nerve plexus in the

176 THE VASCULAR SYSTEM

wall (Elliot). This tone can be increased by vaso-constrictor
and diminished by vaso-dilator impulses. These impulses may
be continuous, resulting from a state of tonic excitation of the
respective centres, which is partly of reflex origin and partly de-
pends on the quality of the blood circulating through the centres,
e.g. by the percentage of and CQ, in the blood. Bayliss finds
that in depressor reflexes there
is, along with inhibition of tone
in the vaso-constrictor centres,
an excitation of the vaso-
dilator centres, and that in
pressor reflexes along with ex-
citation of constrictors there
is under appropriate conditions

inhibition of dilator tone.

When an afferent nerve
from any particular organ is
excited there is produced along
with the usual pressor reflex on
the general blood pressure a
vaso-dilatation in the organ
itself. By this means the
maximal supply of blood is
sent to an active organ. In
these local or Lovén reflexes
as they are called, Bayliss
finds evidence of both excita-

_Fic. 23.—F, depressor; R, pressor tion of dilators and inhibition
afferent nerves affecting arteriole muscle :
through C.C., constrictor, and D.C., of constrictors. Chloral .and
dilator centres, as shown by + and - signs ghloroform convert pressor into
_ (Bayliss).

depressor reflexes, acting not

on the afferent neurone, but on some point in the reflex arc,
probably the synapse.

It is not possible to cause a great fall of arterial pressure merely
by severe sensory excitation in an etherised and morphinised
animal, The pressure falls lower the longer the animal is kept
aneesthetised on the table exposed to cold, to chloral or chloroform,
or to operations which expose large surfaces and lead to actual loss
of blood fluid or to obstruction of venous return, vaso-dilatation,
congestion and transudation. Opening the abdomen and exerting

AND BLOOD PRESSURE 177

traction on the intestines is the most certain method of producing
fall of pressure. The shock produced by severe injuries or operations
is probably, therefore, of the same nature as collapse produced by
bleeding. In man after a severe
injury owing to the shock to the
sensory synapses, there is loss of
reflex tone, and relaxation of both
skeletal and vascular muscle. The
entire cessation of movement leads
to the pooling of blood in the peri-
pheral fields, and at the same time
the injury may entail considerable
~ loss of blood fluid. Toxic products
of altered metabolism probably arise
in the cooled and stagnant blood
which secondarily poison the ner-
vous system. Adrenalin and pitui-
tary extract by constricting the
arteries restore the blood pressure,
the former for a brief, the latter
for a much longer time (Mummery
and Symes).

Chloroform, says Bayliss, con-
verts pressor into depressor reflexes
in the rabbit by reversing the usual
excitation of constrictors into inhibi-
tion. Strychnine, he says, converts
the inhibitory phase of all reflexes
into excitation ; thus the depressor
nerve produces a rise instead of the
usual fall under full doses of strych-
nine. The constrictor centre is ex- yg, 24. , constrictor; D,
cited by the mechanism which dilator neurones; A, arterial

: normally inhibits it. The first B, alleeat uaced ai tibery inhaese
, effect of a small dose in the normal ing bulbar and spinal centres as
animal is to increase the action of “"°Y™Y + and —signs (Bayliss).
the vaso-constrictor centre on the viscera and dilate the cutaneous
vessels. The synapses of the pressor fibres with the constrictor
centre are the first to show paralysis as the dose is increased.
Thus the usual pressor effect which follows excitation of a sensory

- M

178 THE

nerve then becomes depressor.

VASCULAR SYSTEM

By increasing the cardiac power,

and the action of the skeletal muscles, those of respiration in

arterial
E, after

on

cond dose ;

D, of se

ffect of excitation of anterior crural nerve

4

E
t of first dose of strychnine ;

).

A, under ether; B, after chloral; C, effec
Bayliss

Fic. 25.—Antagonism of chloral and strychnine.

strychnine

pressure,

sound and rational. method of
are to fill the heart, increase

signs of recovery.

particular, strychnine may act
favourably.

Those who, like Crile, main-
tain that strychnine is useless
as a drug in shock can argue
that the constrictor synapses are
easily paralysed in this condition
by the drug, and thus it may
accentuate rather than alleviate
the fall of arterial pressure, for
it will then excite the vaso-
dilators which supply all parts,
and the limbs in particular. The
cutaneous dilatation will favour
the loss of body heat. Bandaging
the limbs and particularly the
abdomen partly restores the
arterial pressure and _ cerebral
circulation in a rabbit, which
has been fixed in the vertical
position, as it does in the dog
chloroformed or collapsed from
loss of blood. Crile has intro-
duced a rubber pneumatic suit
for confining the body in states
of shock. An equable air pres-
sure is kept up so that the
arterial pressure measured with
the sphygmometer is restored.
Flaps are arranged in the dress
which can be removed for the
surgeon to operate. The pres-
sure of the air can be reduced
gradually as the patient shows
This seems a
treatment. The objects in view
the resistance in the arterioles,

and compress the capillary-venous areas of the limbs and trunk

AND BLOOD PRESSURE 179

so that the cerebral, coronary, and pulmonary vessels are well

Direct transfusion of human blood from artery to vein has been
used by Crile in extreme cases of simple shock. It is unwise to
use this in any state of toxemia, for hemalysins may then
come into play. Injection of physiological saline is found a
valuable aid.

In collapse brought about by the Sr ae of bacterial toxins,
it is said, the synapses of the vaso-motor centre are at fault, so
that neither excitation of a sensory nerve nor asphyxia provoke
any rise of arterial pressure, while compression of the abdomen or
of the descending aorta provokes it, showing that the heart is not
exhausted and can still respond with increase of energy to better
filling, and increased resistance to its output (Romberg).

Rabbit : 0°2 gm. Chloral intra-venously injected.

|

Excitant. Arterial Pressure.

Mm. Hg.

eae 565

Sciatic faradised 1280
Abdomen massaged 147-0
Aorta compressed . 153-5
Asphyxia : 139°5
Sus 815

Splanchnic nerves divided.

ses | 340

Sciatic faradised 34°5
Abdomen 119°0
Aorta compressed . 1320
Asphyxia 27°5
eee 33°0

Chloral injected again.

ds _ 20-0

. Abdomen massaged . | 66:0
Aorta compressed . 52-0

23°0

These figures show the relative effect of paralysis of vaso-motor
nerves and of damaging the heart ka chloral, and with them the

following may be contrasted : _

i

180 THE VASCULAR SYSTEM

Rabbit ; 1:2 c.m. Diphtheria Toxin injected.
Collapse after Diphtheria Toxin.

Excitant. Aortic Pressure.

Mm. Hg.

ie 39°0

Sciatic faradised . a 47°0
Abdomen compressed. 81:0
Asphyxia ° “6 310

Last stage of collapse

Ms 175

Abdomen compressed. 62-0
Asphyxia : : : 18-0

Mr. H. P. Dean informs the writer that in spinal anesthesia
produced by Stovain (injected into the lumbar part of the spinal
canal), the sensory anesthesia spreads upwards to a higher level
than the motor paralysis, and the medullary centres are unaffected
or almost so when the anesthesia has spread even to the head.
The sensory synapses are the first to fail. The blood pressure
falls some 20 mm. Hg only, showing that the visceral vaso-
constrictor nerves are maintained in good state. To sum up
then, the condition of shock or collapse is associated with cessation
of the reflexes which maintain the body in a state of vascular
tone and muscular activity. Hence the stagnation of the blood,
fall of blood pressure, and loss of body heat.

BIBLIOGRAPHY

Carrel, Journ. Exper. Med., ix., p. 226, 1907.
MacWilliam, Proc. Roy. Soc., lxx., p. 109, 1902.
Lister, Brit. Med. Journ., 1899, 1, p. 924.

W. Russell, Arterial Hypertonus, Sclerosis and Blood Pressure, 1907.
G. Oliver, Studies in Blood Pressure, 1908.

Roy and Adami, The Practitioner, xlv., p. 32.

Howell and Brush, Bost. Med. Surg. Journ., cxiv., 146, 1901,

C. J. Martin, Brit. Med. Journ., 1905, 1, p. 870.

Erlanger, Amer. Journ. of Physiol., x., 1904.

McCay, Lancet, 1907, i., p. 1484.

Dahlgren and Kepner, The Principles of Histology, Macmillan, 1908.
Thoma, Textbook of General Pathology, Trans. A. Bruce, 1896,

AND BLOOD PRESSURE 181

y
Roy and Brown, Journ. of Physiol., 2, p. 323, 1879-80.
V. Recklinghausen, Arch. f. Exp. Path. in Pharm., 55, 375, 1906.
Lewy, Arch. f. d. ges. Physiol., 65, 447, 1897.
Stewart, Manual of Physiology, 1895, p. 59.
Leonard Hill, The Phys. and Path. of the Cerebral Circulation, London,
1896. Cerebral Anewmia, Trans. Roy. Soc., Journ. of Physiol., xxvii.,
p- 337, 1901; and xxviii, p. 122, 1902. Article Circulation, Schifer’s
Textbook of Physiology, vol. ii., 1900.
T. Henderson, Ophthal. Soc. Trans., xxviii., 1908. The Ophthalmoscope,
s Oct. 1908.
| 7’. Lewis, Journ. of Physiol., xxxviii., p. 240, 1908.
Tigerstedt, Ergeb. der Physiologie, vi., p. 269.
E. Weber, Arch. f. Physiol., 1907, p. 300.
Mosso, Die Furcht, 1889.
Bainbridge, Practitioner, lxxv., p. 633, 1905.
Sollmann, Amer. Journ, of Physiol., 1905, 13, p. 241.
Bolton, Journ, Path. and Bact., 1903, p. 67.
Stewart, Guthrie, dc., Journ. Exper. Med., viii., 289, 1906 ; x., 371-490,
1908.
Cohnheim, Vorlesungen iiber Allgem. Pathologie, 1882.
Worm-Miiller, Transf. u. Plethora, Christiania, 1875.
R. du Bois Raymond, Brodie, and F. Miiller, Arch. f. Physiol., 1907,
Suppl. Bd., p. 37.
Starling, Schifer’s Physiology, 1, 285, 1898.
Bier, Hyperamie als Heilmittel, 1903, Leipzig.
A. Wright, The Practitioner, Ixxx., p. 600, 1908.
Sherrington, The Integrative Action of the Nervous System, 1906.
Porter and Quinby, Amer. Journ. of Physiol., xx., p. 500, 1907-8.
Bayliss, Proc. Roy. Soc., 80, p.339, 1908.
Elliott, Journ. of Physiol., 32, 401, 1905.
Crile, Blood Pressure in Surgery, 1903.
Mummery and Symes, Brit. Med. Journ., Sept. 19, 1908.
Romberg, Piissler, &c., Deutsch. Arch, f. Klin. Med., Bd. 64, p. 652, 1899 ;
Bd. 77, p. 96, 1903.

For a general list of recent literature consult Heinz. Handb. der exper.
P: Path, u. Pharm., vol. 2, p. 283.

THE MECHANISM OF RESPIRATION IN MAN

By ARTHUR KEITH.

THE following is a summary of the chief points dealt with in this
article :—

(1) The lung is composed of elements of varying degrees of
extensibility ; hence the expansion of its parts are unequal
during inspiration.

(2) The infundibula or air sacs are the essential distensible —
(inspiratory) elements of the lungs. The distensibility of any part
of the lung will depend on the number and size of the infundibula
in that part.

(3) The bronchial musculature regulates the tension of the
infundibular air and may regulate the distribution of air and
blood throughout the lung.

(4) The lungs do not expand equally in all directions, but
execute a movement in certain definite directions during in-
spiration.

(5) The roots of the lungs are not fixed but undergo a res-
piratory movement.

(6) The great fissure of the lung is of functional significance.
The upper lobe is chiefly expanded by a mechanism formed by
the upper ribs, the lower lobe by a compound mechanism formed
by the diaphragm and lower ribs.

(7) Expiration is controlled by muscular action.

(8) The extensibility and elasticity of the thorax are factors
in producing expansion or compression of the lung only when
the ribs pass into extreme inspiratory or expiratory positions.

(9) Tue first pair of ribs and the manubrium sterni are parts
of a single mechanism which may be described as the thoracic
operculum. The sterno-manubrial joint is of functional im-

. portance.

(10) In observing and analysing the respiratory mowseiiaitl
of the thorax it is advantageous to treat the costal cartilages
aa)

\
\
\ .
\
\

RESPIRATION IN MAN 183

and their musculature as an individual part of the respiratory
mechanism.

(11) The diaphragm acts as a true piston, moving the ab:lominal
contents downwards and forwards, the direction depending on the
type of respiration. The effect of its contraction depends on the
action of its antagonists.

, (12) That in describing the movements of the ribs it is neces-
4 sary to recognise at least two types, one representative of the
upper costal mechanism and the other of the lower or diaphrag-
matic mechanism. The movements of the lower set are correlated
with the action of the diaphragm; those of the upper set work
independently of the diaphragm.
(13) The floating ribs (eleventh, twelfth, and often the tenth) are
functionally parts of the abdominal wall.
(14) The articulations, muscles, movements, and conforma-
tion of the ribs of the lower set differ widely from those of the
. upper set.

(15) The action of the intercostal muscles depends on the
antagonists brought into use. Some intercostal spaces are
widened and some diminished during inspiration, and the same
is true during expiration. ;

(16) The levatores costarum have no action on the ribs; they
are purely spinal muscles.

In this article the writer proposes to summarise certain recent
papers dealing with the respiratory expansion and contraction of
the human lungs. The evidence contained in these papers is
derived from three sources: (1) From measurements of the res-
piratory movements of the body wall by photography, by X-rays,
by recording tambours, by direct measurements, or by tracings

’ taken with strips of lead moulded on the body. When possible the
| writer has selected those observations which deal with the normal
| unconscious respiratory movements rather than records made on
--—s conscious subjects taking exaggerated breaths. (2) From observa-
tions on the anatomy of parts concerned in respiratory Move-
| ments, for whatever theory be adopted of these movements, it
must give a rational and complete explanation of the form and
arrangement of the structures concerned in them. (3) From clinical
observations made by means of percussion and auscultation. When
the evidence from these three sources is summarised it is found

184 THE MECHANISM OF

to necessitate a considerable alteration in our current teaching
of the mechanism of respiration.

THe EXTENSIBILITY AND ELasticiry oF THE LuNG

It is usually presumed that the lungs are equally extensile
throughout, but an examination of their structure shows that this
cannot beso. From an anatomical point of view the lung may be
divided into three zones: (1) A root zone containing the bronchus,
artery, and vein, and their main divisions, with lymphatic glands
and vessels, and much fibrous tissue, all structures offering great
resistance to a distending force. (2) An intermediate zone in which
vascular and bronchial ramifications radiate towards the surface
of the lung with pulmonary tissue implanted between the rays.
It is a zone containing structures of varying degrees of extensi-
bility, the veins being the least extensile and the pulmonary tissue
the most. (3) An outer zone, estimated roughly at 25 to 30 mm.
in depth, which expands much more freely and equally than the
intermediate zone. Perhaps the subpleural stratum of the outer
zone should be distinguished, for if a lung, which has been re-
moved from the body, be gradually inflated, it will be found that
the subpleural stratum is at first elevated at certain points into
plateaux about 2 mm. above the surface of the lung, and from
these elevated points the process of distension of the subpleural
stratum spreads out in all directions. This at first appeared to
be due to a more complete collapse of the subpleural air sacs, but
microscopic sections show that in the collapsed condition these
sacs are still as large as the deeper, so it may be concluded that,
when distended, they are larger than the deeper sacs, and collapse
to a greater degree. Seeing that the lung is intersected with
radiating bronchio-vascular rays, of a much lower degree of
extensibility than the pulmonary tissue between them, one must
suppose that these rays during the inspiratory expansion of the
lung must move apart so as to permit the pulmonary tissue lying
between them to expand. A consideration of the anatomy of the —
lung and of its movement during inspiration shows that the
expansion of the lung is not the simple dilatation it was believed
to be; its expansion is a regulated act resembling more the
opening of a Japanese fan than the distension of a simple elastic
sac. Among recent writers, Tendeloo is the only one to emphasise

RESPIRATION IN MAN 185

the varying degree of extensibility of the structures of the lung.
In all mammalian lungs the veins and arteries occupy a definite
and constant relationship to the bronchial ramifications—a relation-
ship which must have a functional significance. Amongst the
various means the writer employed to estimate the extensibility of
| the several parts and structures of the lung was that of marking the
| surface of the partly inflated organ with points placed at regular
intervals, and then measuring the distances bctween these points
when the lung was more fully inflated. The parts of the lung
which were found to expand most were the central areas of the
costal and of the diaphragmatic surfaces. The method was.
abandoned because it was found that the expansion obtained by
inflating the lung did not correspond to the expansion of the lung
by means which imitated the normal action of the thoracic walls.
Hutchinson discovered long ago that the form assumed by the
thorax when the lungs are inflated after death, differs altogether
from the inspiratory position of the thorax. His observation,
however, has been forgotten, and models of lungs so inflated are at
present the only ones on the market. Several anatomical papers
have been published recently giving the inspiratory position of the
apices of the lungs, that position being determined by artificial
inflation of the lung. In the dead body the lung, when inflated, -
expands in the direction of least resistance.

On THE FUNCTION AND NATURE OF THE INFUNDIBULA

Closely related to the extensibility of the various elements of the
lung is the question of the function and nature of the infundibula.
In the most valuable work recently published by Oppel the use of
the term infundibulum is condemned. He prefers to follow Miller
; in distinguishing the following terminal air spaces in the lung :—
| (1) The terminal bronchiole, with its sphincter-like arrange-
ment of musculature ; (2) the vestibule; (3) the atrium; (4) the
air sacs; (5) the alveoli implanted on the walls of the air sacs.
) Such an elaborate nomenclature obscures the functional nature
; of the final pulmonary elements, for while the terminal bronchus
is one functional element, and the alveoli another, the vestibule,
the atrium, and air sacs combined form but one element, namely,
the essential distensible air spaces of the lung (bellows part), and
it is well to retain the term infundibulum to designate the com-

186 THE MECHANISM OF

plex space in which a terminal bronchiole ends. In the frog’s
lung the central space represents the infundibular element of the
mammalian lung; in reptiles it is represented by the thin walled
posterior part of the lung; in birds it is represented by the air
sacs ;*in the mammalian lung the distensible elément is scattered
throughout the lung, whereas in all other vertebrate it forms a
separate part. If out of a rubber balloon a model of the terminal
bronchiole infundibulum and alveoli be made and inflated, it is
the central or infundibular space which expands most, the alveoli
implanted on its walls being widened but at the same time ren-
-dered more shallow. The point which one seeks to emphasise
is that it is not the alveoli but the infundibula that should be
regarded as the essential expansile parts of the lung; the larger
and more plentiful the infundibula in a part of the lung, the more

readily will that part respond to any distending force. Oppel ©

gives the diameters of the infundibula in the apical part of the
lung as ‘12 mm. at the third year and -45 mm. at the seventieth ;
in the basal part of the lung as ‘38 mm. at the third year and -85
mm. at the seventieth. They are largest in the subpleural zone
and smallest in the root zone. One infers, therefore, that, when a
breath is taken, the base expands more readily and to a greater
extent than the apical part, and the subpleural more than the part
at the root. When emphysema occurs it is the infundibula which
first become hyperdistended, and the parts most liable to emphysema
are those in which the infundibula have normally the greatest size.

THE BRONCHIAL MUSCULATURE

The older physiologists regarded the bronchial musculature as
expiratory in function; even now most medical writers ascribe
the reflex contraction of the lung (Abram’s reflex) which follows
any stimulation of the chest wall to the action of:the bronchial
musculature. It is more probable that the retraction of the lung
is due to a reflex contraction of the musculature of the body wall.
The action of the musculature of the bronchioles in regulating
the tension of the air within the infundibula has not received the

attention it deserves. The more the calibre of the bronchiole is —

diminished during inspiration the greater must be the negative
tension within the infundibula, a tension which must act on and
distend the capillaries and various blood spaces embodied in the

a

RESPIRATION IN MAN 187

walls of the infundibula. The bronchial musculature by diminish-
ing or increasing the access to the infundibula in various parts
of the lung may regulate the distribution of the indrawn air
throughout the lung. By regulating the intra-alveolar pressure it
may also influence the distribution of blood throughout the lung,
and take the part of the vaso-motor mechanism which has not
been proved to exist in the lung.

Tue NEcEssIty OF RECOGNISING SuRFACES OF Direct EXPANSION
AND SURFACES OF INDIRECT EXPANSION ON THE LUNG

The lung is usually regarded not only as being equally dis-
tensible in all its parts, but also of expanding equally in all
directions during inspiration. This is far from being true of the
mammalian lung. Of the five areas which one may distinguish
on the surface of the human lung, three are in contact with
stationary parts of the thoracic wall, and therefore cannot be
directly expanded. These three pulmonary surfaces are—(1) The
mediastinal, in contact with the pericardium and structures of the
mediastinum ; (2) the dorsal surface, in contact with the spinal
column and with the spinal segments of the ribs—those parts of
the ribs to which the erector spine is attached; (3) the apical -
_ surface, the pulmonary area lying in contact with Sibson’s fascia
at the root of the neck. It is not strictly true to say that these
three parts of the pleural wall are stationary, for the heart being
conical in shape, with its base resting on the diaphragm, it is clear
that the mediastinal surface of the lungs may expand inwards
with the inspiratory descent of the heart; only the dorsal part
of the apical surface is stationary, for the ventral or anterior part
is elevated with the first rib, but the fact remains that during

4 inspiration the apical resonance does not extend into the neck
) but decreases (Colbeck), and by placing a tambour on the neck
over the apex of the lung it is found that the apex descends when-
ever the diaphragm is well in action, even if the first rib remains
| stationary. The two surfaces of the lung which are directly~ex-
| panded are the diaphragmatic and ventro-lateral or sterno-costal.
Thus if the diaphragm and lower ribs are in action the whole lung
is expanded in a downward and forward direction, the apical
surface remaining stationary or descending until the structures
of the neck become sufficiently tense to resist a further descent.

188 THE MECHANISM OF

The negative tension, in such an inspiration, falls first and most
in the basal part of the lung; hence one finds very frequently a
horizontal groove (Harrison’s sulcus) on each side of the thorax
corresponding to the level of the domes of the diaphragm and
to the zone of greatest negative pressure in those who have had
the respiratory passage obstructed. Meltzer found the degree of
negative pressure within the thorax of rabbits increased as the
diaphragm was approached ; it is least along the stationary walls
of the thorax. It is thus apparent that a certain degree of the
expanding force transmitted by the thorax to the surfaces of direct
expansion is lost as it passes through the lung to the surfaces of
indirect expansion. Further, the extent to which any part of the
lung is expanded depends on the distensibility of that part, being
greatest in the superficial zone of the lung and least in the root
zone. That the expansion of the lung does not take place instan-
taneously and equally throughout all its parts is well substantiated
by clinical observation. Huggard and Clive Riviere observed
independently that if percussion and auscultation of the lung
were carried out before a deep breath were taken, the apices of
the lungs, especially in those who were regarded as being the
subjects of a phthisical tendency, were less in action than the
rest of the lungs; Lloyd Jones records that when a breath is
taken the resonance of the anterior part of the apex of the lung
increases much more than the posterior; Gerhardt noticed that
when a pleural effusion was being absorbed the apex of the lung
was the last part to regain its normal resonance. It is a well-
known clinical fact that a localised consolidation is surrounded
by an area of increased resonance, showing that the diminution
of one part of the lung is not followed by an expansion of the
whole lung but only of the part immediately adjacent. When it
is remembered that those who lead sedentary lives use their lungs
to only 10 per cent. or even less of the full pulmonary capacity,
the importance of recognising that a thoracic movement only
affects that part of the lung directly subject to the movement will
become apparent. In those who have contracted a lazy habit of
body it is possible for the parts of the lung which are the most

remote from the surfaces of direct expansion and at the same —

time of a low degree of distensibility, to pass into a condition of
partial or almost complete disuse; such a part is that region of
the apex where phthisis so frequently commences.

RESPIRATION IN MAN 189

RESPIRATORY MOVEMENTS OF THE Roots OF THE LUNGS

The root of the lung has hitherto been regarded as the most
fixed part of the lung, the part from which the expansion of the
lung takes place. Were this so it is manifest that those parts of

x Verteb. Col.------- i a tar aeons
Apex ;

Root (inspir. —

Pericard----@

lower Bord. lexp. :
Lower Bord. (inspir, ce

Crus (inspir)

Crus (expir)

D

Fic. 1,—Mediastinal aspect of the right lung to show the respiratory movement
of the root. The crus of the diaphragm is also indicated, and its attachment to the
root of the lung through the pericardium. The arrows indicate the direction of the
inspiratory movement of the various parts of the lung.

the lung which lie between the root and the stationary walls of
the thorax could undergo no expansion. The truth is that during
a complete inspiration the whole lung, root included, undergoes

a

a definite movement. In the normal mixed inspiration, where
diaphragm and ribs co-operate equally or almost equally, the
lung expands in three directions—downwards, forwards, and out-
wards, the root sharing in the combined moyements. When the
abdominal breathing is well marked, the trachea can be felt de-
scending in the neck as the epigastrium comes forwards. By the
use of X-rays the heart, and therefore the roots of the lungs, for
the heart is bound firmly to them, can be seen to follow the move-
ments of the chest wall; with a thoracic breath, the heart follows
the movement of the sternum; with a diaphragmatic breath, it
descends with the diaphragm. The great muscular crura of the
diaphragm, forming one-third of that muscle, can act directly on
the roots of the lung through the pericardium and heart. In cases
where the roots of the lungs are bound to the posterior or stationary
wall of the thorax through adhesions set up by mediastinitis, ©
Wenckebach observed that both the respiratory and circulatory
movements were abnormal in character.

190 THE MECHANISM OF

THE FUNCTIONAL SIGNIFICANCE OF THE: DIVISION OF THE
Lunes Into LoBEs

Tt is usually said that the division of the lungs into lobes has
no functional significance. This opinion is founded on the fact
that they may be only partially developed or completely oblite-
rated by disease without altering the functional capacity of the
lung. The obliteration of the pleural cavity by adhesions has so
little apparent effect on the respiratory movements that their
presence cannot be detected during life. In one case, where
the lungs were completely adherent, Hutchinson found the vital
capacity to be 680 cc. above the average amount. This method
of reasoning is liable to lead one into great error, for there are
many functional organs in the body which may be removed with-
out any marked disturbance of the bodily economy. When the
normal respiratory movements of the lung are fully understood
it will be found that the great fissure, which divides the upper
from the lower lobe, is functional in its significance. The upper
lobe is normally expanded by one mechanism, the lower by
another. When the lung is removed from the body and slightly
inflated there will be seen marked out on the lateral and anterior
aspects of the upper lobe—especially in the lungs of women— 4

ale

RESPIRATION IN MAN 191

- the impressions of the first, second, third, fourth, and fifth ribs

and costal cartilages. These impressions are marked in two ways :

the part of the lung lying under the rib is less pigmented and is

grooved ; the zones corresponding to the intercostal spaces are
more pigmented and are elevated above the level of the costal
zones. To obtain such results, for these marks cannot be post-
mortem effects, the relationship of the upper lobes to the upper
ribs must have been stationary during life; there could have
been no gliding of the lung across the ribs and spaces during
inspiration and expiration. But on the lower lobe, except for
an occasional impression of the seventh costal cartilage, at the
anterior angle, these costal impressions are absent; the pigment
is evenly distributed, or if not, does not correspond to spaces. The
inference one draws is that the lower lobe glides beneath the ribs
during the respiratory movements ; there is not, as in the upper
lobe, a constant relationship between ribs and spaces. But it
must be noted, too, that the dorsal surface of the upper lobe does
not show these costal impressions; here, too, there must be a
downward and upward movement, one which I had inferred to
take place before my attention was drawn to the costal markings
as a guide to the respiratory movements of the lung. When
dealing with the movements and mechanism of the ribs it will
become apparent that the lower lobe and the dorsal part of the
upper lobe are chiefly expanded by a diaphragmatic mechanism,
and the upper lobe by the upper five ribs. It must not be sup-
posed that these markings are to be found on the lungs of every
individual; they are constant in the lungs of women, and their
frequent absence on men’s lungs can be understood when one re-
members how many there are that obtain their chief inspiratory
expansion by a moderate use of the diaphragmatic mechanism
alone. Pleuritic sounds and pleuritic pains are most intense
over the lower lobe; Fowler and Pasteur have recorded cases
of paralysis of the diaphragm where the collapse was confined to
the lower lobe. The upper lobe is always relatively larger in
women than in men, a result to be expected from their manner
of breathing. It is true that pleuritic friction can frequently be
detected over the upper lobe; this fact must certainly be taken
into consideration, but it must be remembered that a localised
pleurisy has a powerful reflex influence on the respiratory muscu-

lature corresponding to that part, and it is therefore probable that

192 THE MECHANISM OF " 4

there is a grave disturbance of the normal respiratory movements
in such cases.

THE ACTION OF THE RESPIRATORY MUSCULATURE IN
NorMAL EXPIRATION

A consideration of the evidence now at our disposal makes it
difficult to believe that normal expiration is merely the result of
an elastic recoil. The recoil is evidently under muscular control.
The antagonist of the diaphragm is the musculature of the belly
wall; it is difficult to believe that the replacement of the dia-
phragm and the abdominal viscera at the end of an inspiration
is merely an elastic recoil of the abdominal musculature. One
cannot deduce the elasticity of a living muscle from the study of
the dead, but I may put on record here the following observation. —
A piece of the human rectus abdominis 135 mm. long stretched
to 180 mm. when a weight of 10 kilos was attached to it; on
removing the weight it had retracted in five minutes to 150 mm.
It is improbable that the muscles which are attached to the ribs
are carried by the ribs as passive burdens during expiration. The
reflex co-ordination which Sherrington has shown to exist between
so many antagonistic groups of muscles, probably holds true also
for the inspiratory and expiratory groups of muscles. Duchenne
found that the abdominal musculature was brought into action
when the phrenic nerve is stimulated. Spina and Mislawsky
observed that stimulation of the apparent fibres in the phrenic
had an inhibitory action on the abdominal musculature. Baglioni
obtained an expiratory movement of the body wall when the dia-
phragm itself was stimulated. At least one can feel the upper part
of the rectus abdominis harden under the fingers during expiration,
as if it were inaction. The observation of Treves, the Italian physio-
logist, also points to expiration being a muscular act. He found
that if an inspiration is arrested, it is followed by an expiration of
normal amount. Mosso observed that the respiratory movement
became thoracic in type when the horizontal position was
assumed, a result which cannot be ascribed to an alteration in
the elastic recoil of the lung. Mosso concluded that the assump- —
tion of the thoracic type of respiration in the supine position is |
brought about through a reflex action of the vagus, but in the
writer’s opinion the change is due to an alteration in the

°

“a
)
4
}
j

RESPIRATION IN MAN 193

action of the expiratory muscles. The erect posture neces-
sitates an increased action of the musculature of the belly wall
in order. to balance the body, the ribs being thus more firmly
fixed than in the supine position; with the assumption of the
supine position the musculature of the belly wall is relieved of
its postural function, thus lessening the strain on the ribs and
allowing them to move more freely. If expiration were an elastic
recoil uncontrolled by muscular action one would expect the thorax
to diminish simultaneously in all its parts; this is not so, for ex-
piration like inspiration is a definite movement commencing in the
upper or lower part of the thorax and spreading gradually to the
rest. Those who regard normal expiration as a result of the elastic

recoil of the lungs cite as conclusive evidence of their opinion

those cases of fracture of the spine or section of the spinal cord
where the diaphragm is the sole respiratory muscle in action. In
such cases the writer has observed that the patient lies on the
back or turned somewhat on the left side; the epigastric move-
ments are greater than normal; pressure of the hand applied to
the epigastrium gives immediate distress and completely alters the
type of respiratory movement, the lower ribs being then raised
and the lower part of the chest expanded. Further, the writer
observed that the diaphragm in such cases is kept in a condition
of over-action; in one case the diaphragm worked some 25 to |
30 mm. below its normal level, thus compressing the abdominal
contents and obtaining a recoil from the weight and tension
of the abdominal viscera. To what extent the tonus of the
abdominal and thoracic musculature is lost in these cases has
not been determined. Mosso has shown that tone varies indepen-
dently of the contractibility, and that the abdominal musculature
possess a high degree of tone. The parietal layer of the peritoneum
is highly extensile and elastic to preserve its smoothness in the
various states of movement.

Tue RESPIRATORY VALUE OF THE ELASTICITY OF ~~
THE THORAX

The degree of elasticity of the living thorax has to be esti-
mated from experiments made on the dead. We now know, from

observations made by the use of X-rays, that the diaphragm is

N

194 THE MECHANISM OF “s

in a position of ultra-expiration after death, and we infer that if
. the elasticity of the thorax is in antagonism to the elasticity of

the lungs at the end of expiration, then the elastic recoil of the

thorax in the dead is an exaggeration of that in the living. Sir

Douglas Powell made observations on ten subjects; he noted the

expansion of the thorax when the pleural cavity was punctured

and the lungs allowed to collapse. In six of these there was no

expansion of the thorax; in four the average expansion forwards
of the chest wall was 2°3 mm. When it is remembered that the

lateral or antero-posterior thoracic expansion varies from 1 to 2

mm. in normal respiration, even in men with the thoracic type of

breathing, it is evident that the elasticity of the thorax can play

but a slight part in normal expiration. Any observation made on

the dead body is vitiated by the rigor mortis and post-mortem

changes of the muscles. I observed that when the muscles are

removed from the thorax that the weight of the ribs and sternum

was enough to cause the thorax to assume an expiratory position

when the body was turned in the feet-down position, and to pass

into the inspiratory position when the body was inverted. One

must conclude from a study of the thorax of the dead that the rib

movements are so free that elastic recoil of the thorax comes to

be a factor in expiration and inspiration only towards the extreme |
limits of respiratory movements.

Recently the writer had reason to compare the elasticity and col-
lapsibility of the thorax in living subjects with that of dead subjects.
The matter has some importance in determining the best method
for performing artificial respiration on the apparently drowned, ©
and also in selecting the position of patients in performing intra-
thoracic operations. Elsberg, for instance, asserts that the pleura
may be opened without collapse of the lung if the patient be
placed in the prone position ; it is certainly possible to reduce the
capacity of the thorax in adult human beings to a point when it
is too small to contain the collapsed lungs, and hence a part is
extruded as a hernia. The writer’s investigations show that the
living and dead thorax react quite differently when compressed,
the difference bemg due, in his opinion, to the reflex action of the
respiratory musculature. The following table gives the results of
his experiments ; the measurements for the living are the average
for ten students varying from eighteen to twenty-four years
of age; those given for the dead are the averages from five

RESPIRATION IN MAN 195

4 dissecting-room subjects varying in age from fifty to seventy-
two years, in whom the compressibility of the thorax is expected
to be greatly diminished.

Results of Compression of the Thorax. Living. Dead,
1. The front-to-back diameter of the thorax was
] diminished in turning from the supine to
the prone position , ; . ‘ . 174mm. 21°4 mm.

2. The side-to-side diameter in the same experi-
ment increased. ‘ ; ‘ ; - 221mm. 135 mn.

3. The front-to-back diameter decreased on
placing 10 kilos. on the thorax (subject
supine) . ° P ‘ , ‘ z . 23°7mm, 29°6 mm.

4. The transverse diameter increased in the same
experiment . ° ° : : : . 56mm. 135 mm.

5. The front-to-back diameter of the thorax de-
creased on placing 10 kilos. on the thorax
(subject prone). ‘ : , , - 128mm. 46mm.

6. The transverse diameter increased in the same
experiment . . : . ; ; - 38Omm. 8°6 mm.

These experiments show that the compressibility of the thorax is —
largely modified by the action of muscles during life, and that in
the prone position a very great degree of the natural elasticity
of the thorax is lost.

Freund, whose observations are receiving active attention in
Germany, after many years of neglect, is of opinion that the
elastic torsion which occurs in the cartilage of the first rib during

inspiration is one of the chief active forces in producing an
7 expiratory recoil of the thorax ; he also regards emphysema as a
result of loss of elasticity of the costal cartilages. His opinion
concerning the expiratory recoil of the cartilage of the first rib
will be referred to in dealing with the sterno-manubrial joint; as
regards the loss of elasticity of the cartilages causing emphysema,
it may be said that surgeons have put Freund’s belief into practice
by section of the costal cartilages in such cases, but the results
of such experiments have not yet been determined. Certainly
calcification of the costal cartilages frequently occurs without
emphysema.

196 THE MECHANISM OF

THe First Ris, MANUBRIO-STERNAL JOINT, AND THEIR
RESPIRATORY SIGNIFICANCE

The first rib has always been treated as merely one of the
costal series. Its articulation to the spine, its ligaments, its
muscles, its shape, its costal cartilage, its intimate union with
the manubrium sterni, differ so markedly from the corresponding
features of other ribs, that were only the anatomical evidence avail-
able, one would conclude that it differed from all the others in
its respiratory function. An examination of its movements and
of the part it plays in expanding the lung shows this is so. The
first pair of ribs and the manubrium sterni are bound intimately

Manub.(exp.)—- ca sy

AW OY
\ Ags

Fic. 2.—Diagram to show the respiratory movements of the first pair of ribs and
manubrium sterni, and the effect of these movements on the expansion of the apex
of the lung. :

together by the broad and short first pair of costal cartilages,
and form with the manubrium, a united structure which may be
described as the lid or operculum of the thorax. Behind, this
lid is articulated to the spinal column by a joint which is set more
transversely and is wider in the extent of its attachment than
any other of the costal arcs; in front the lid is articulated with
the body of the sternum at the manubrio-sternal joint. The
manubrio-sternal joint must be counted amongst the important
respiratory joints. Anchylosis of this joint is rarely seen before
the fiftieth year, and it is uncommon before the sixtieth. The
respiratory movement which occurs at it varies with the indi-
vidual, with the type of respiration, being greatest in. those with

———

RESPIRATION IN MAN 197

the thoracic type, and with the extent of the respiratory move-
ment. Braune estimated its movement at 5° to 13°, Rothschild,
who regards limitation in the movement of this joint as a cause
of consumption, estimated the average movement (in full inspira-
tion) to be 15°85° in the male and 12°85° in the female ; while the
writer, who was unaware of Rothschild’s observations, found it
varied from 1° to 16°. The degree of movement depends chiefly
on the inspiratory behaviour of the body of the sternum, which
is extremely variable. In some individuals the lower end of the
sternum during the elevation of the thorax during inspiration may
be drawn towards the spine or move forward to a less degree than

the upper end of the body of the sternum; in such, the sterno-
- manubrial movement is free. If, on the other hand, the lower
end of the sternum moves more freely away from the spine than
the upper end, the movement at the joint is less extensive. At
the sterno-manubrial joint, the operculum or lid of the thorax
articulates with the anterior thoracic wall. The prominence of this
joint on the surface of the thorax is extremely variable—so many
conditions may render it unduly prominent. Ludwig, the Parisian
physician, is said to have regarded an undue prominence of the
articulation (Angulus Ludovici) as an indication of phthisis ; but
researches made by recent German writers have failed to trace -
such a statement in Ludwig’s writings. Rothschild found that
the sterno-manubrial movements were limited or absent in
phthisical subjects, and ascribed the susceptibility of the apex to
phthisis as due to an anchylosis or limitation of movement at this
joint. In his opinion a free manubrio-sternal movement is neces-
sary if the apex of the lung is to be properly expanded. Freund
attributes the incomplete expansion of the apex in the phthisical
action to a congenital shortening and ossification of the cartilage
of the first rib. It is true that the necks of the first pair of ribs
are so articulated to the spine that with the elevation of the
manubrium sterni there is some degree of torsion of their cartilages,
but the amount of the torsion is slight in extent because of the
particularly loose manner in which the heads of those ribs are —
bound to the first dorsal vertebra. The writer, unaware of the
observations and theories of Freund and Rothschild, had concluded
that the ossification of the first costal cartilage and limitation of
the sterno-manubrial movements were consequences rather than
_ causes of a limited expansion of the apices of the lungs. In

198 THE MECHANISM OF |

dealing with the significance of the division of the lungs into lobes,
the direct influence of the diaphragm on the apices of the lungs
has been already pointed out. The upward movement of the
first pair of ribs and manubrium expand chiefly the anterior or
ventro-lateral part of the apex of the lung; the movement has
but an indirect influence on the dorsal part of the apex, espe-
cially that part lying in front of the necks of the first and second
pair of ribs. It is the dorsal part of the apex of the lung that
is the common initial site of pulmonary tuberculosis. To secure
a free expansion of that area of the lung a full diaphragmatic con-
traction is much more effective than any movement of the upper
thorax.

THE RESPIRATORY MOVEMENTS OF THE CosTAL CARTILAGES

In man, and it is true of nearly all mammals, the costal carti-
lages progressively increase in length and in their declivity to the
sternum as one passes from the first downwards. The following are
the lengths of the cartilages in millimetres of a well-built man
from the first to the ninth ribs :—first, 25; second, 37; third, 50;
fourth, 62; fifth, 75; sixth, 87; seventh, 112; eighth, 137;
ninth, 160. Although the eighth and ninth cartilages do not
directly reach the sternum, yet for functional purposes they really
do through their close union with the seventh costal cartilage,
and hence their length is estimated as if they did reach the
sternum. The costal cartilage of the first rib descends to reach
the sternum; that of the second normally lies horizontal and joins
the sternum at a right angle; the third ascends to the sternum,
and the degree of ascent becomes greater with each succeeding
cartilage until, at the lower end of the sternum, the seventh pair
of costal cartilages form together the subcostal angle which varies
from 45° to 90°, 65° being a common size in well-formed adults.
In observing the respiratory movements of any individual it is well
to regard the costal cartilages as a separate part of the respiratory
mechanism ; they have their own muscles ; during inspiration the
interchondral muscles (anterior part of the internal intercostals)
and the anterior digitations of the diaphragm raise them into a
more horizontal position, increasing the transverse diameter of the
thorax and the size of the subcostal angle. The cartilages are
depressed and the subcostal angle decreased by the upper part of

RESPIRATION IN MAN 199

the transversalis and triangularis sterni; the rectus abdominis

also depresses the cartilages, but its action, owing to its peculiar

insertion, is really that of a depressor of the whole thorax.
Measurements of the respiratory movements of the subcostal
angle are useful in distinguishing between’ an inspiratory move-
ment effected by an upward movement of the thorax as a whole,
and one in which the upward movement is accompanied by a
tilting upwards of the outer ends of the cartilages. For instance,
during a forced inspiration, in three individuals, selected at random,
the increase at the subcostal angle was 6°, 9°, and 30°. Unfor-
tunately nearly all the observations published on the movements
of this angle relate to forced inspiration ; in quiet inspiration the

increase is about 1:5° for those with an abdominal type of respira-

tion, and about half that amount in those with a thoracic type.
The writer, from observations made by the aid of X-rays, has
come to regard a free movement of the subcostal angle as an index
of a free action of the diaphragm.

Tue AcTION AND MOVEMENTS OF THE DIAPHRAGM

In recent years anatomists have had an opportunity, thanks
to the discovery of Rontgen, of correcting their inferences as to
the action of the various parts of the diaphragm by direct obser- —
vation on the living. When tested in this way the elaborate
deductions of Hasse as to the internal respiratory movements have
proved to be remarkably near the truth. He inferred that the
central or pericardial part of the diaphragm must also participate
in all respiratory movements, that the diaphragmatic movement
as a whole must be in a forward as well as in a downward direc-
tion, and that all diaphragmatic movements were accompanied
by a definite movement of the abdominal viscera. The writer
has shown that the diaphragm is made up of two parts which are
different in origin, different in their nerve supply, and different in
their action. These two parts are the spinal or crural part, the
fibres of which arise from the spinal column and arcuate ligaments,
and ascend to be inserted into the posterior or concave margin of
the central aponeurosis; these fibres are normally from 125 to
150 mm. long, and weigh about 60 grammes. The other part of
the diaphragm—the sterno-costal—weighs about 96 gramines ; its

several digitations vary in length, that from the ninth costal car-

200 THE MECHANISM OF

tilage being longest; the fibres pass backwards as they ascend.
Thus while the spinal segment of the diaphragm tends to elongate
the thorax in a vertical direction, the sterno-costal part pulls
forwards and downwards the abdominal viscera, increasing the
back-to-front diameter in the lower part of the thorax. The
resultant movement of the diaphragm is one in a downward and
forward direction ; the more the thorax is elevated the greater is
the forward visceral movement; the more the downward move-
ment, the more are the abdominal viscera depressed. The writer
has observed in patients who were described clinically as neuras-
thenic, that the spinal part of the diaphragm may act forcibly
while the sterno-costal part is almost passive. Duchenne showed
conclusively that if descent of the abdominal viscera is restrained

the diaphragm spent its force in elevating the thorax. Dally |

observed, and the observation has been frequently verified, that
the curvature of the domes of the diaphragm is scarcely altered
during even a profound inspiration. We have come to see that
the diaphragm, rendered semi-solid by the abdominal viscera and
having its circumferential zone kept constantly applied to the
inner wall of the lower part of the thorax by the negative intra-
thoracic pressure, acts as a true piston—a piston moving in a
downward and forward direction, the lung expanding into the
space it vacates. The action of the diaphragm depends on which
group of muscles comes into play as its antagonists. If the
abdominal contents are rendered fixed by the abdominal muscu-
lature, the lower margin of the thorax moves towards the domes
of the diaphragm ; if, on the other hand, the ribs are fixed by the
intercostal muscles, and the abdominal musculature is reflexly
relaxed, the domes of the diaphragm move towards the lower
aperture of the thorax. In subjects of extreme visceroptosis
Wenckebach observed that the diaphragm was thrown out of
action by its visceral fulcrum being lost, and breathing was carried
on by an elevation of the upper part of the thorax. Seeing how
variable the action of the diaphragm is in the same individual,
and how much it differs in its action from individual to individual,
it is rather misleading to make any precise statement of the ampli-
tude of the movements of its domes. In quiet breathing Dally
found, by the use of the orthodiascope, that the mean descent
of the right dome in 100 individuals was 12°5 mm.; the left
dome, 12 mm.; the central part rather less than the left dome.

RESPIRATION IN MAN 201

Hultkranz estimated the average inspiratory descent of the whole
diaphragm at 10°5, Guillemot at 15 to 18mm. About half an inch
is its ordinary descent, the right dome moving rather more than
the left, and the left more than the central part. From Hutchin-
son’s, Dally’s, and my own observations the area of the diaphragm
in contact with the lungs may be estimated at 250 sq. cm. A
descent of 10 mm. all over gives an increase of 250 c.c. of thoracic
space ; if one estimates an average quiet breath at 400 c.c. it will
be seen that the diaphragmatic movement plays a larger part
than the costal movement. Hultkranz estimated that in taking
a breath of 490 c.c. 170 was the result of the diaphragmatic, and
320 of the thoracic movement. Sewall and Pollard found that a

larger breath could be taken by a thoracic inspiratory movement
than by an abdominal one. R. T. Mackenzie has again verified
Hutchinson’s observation that there is no relationship between
the extent to which the chest can be expanded in circumference
and the amount of breath that is thereby taken in. The thorax
can be enlarged so that the abdominal viscera instead of air is
drawn into the thoracic cavity. At the London Hospital there
was an old acrobat who could draw in this way all his abdominal
viscera up into the thorax, so that the abdominal aorta was felt

_ pulsating under the fingers from the epigastrium downwards. -
When the thorax is expanded beyond the extensibility of the lungs
the abdominal viscera are drawn upwards to occupy the thoracic
space; highly trained gymnasts at the army schools invariably
obtain their great chest expansions in this way. .

a

THE RESPIRATORY MOVEMENTS OF THE RIBS

In describing the respiratory movements of the thorax most
teachers restrict their description to a typical rib, in order to
secure simplicity of description. Two movements are recognised,
one round an axis corresponding to the spinal articulation of the

_ rib, and another round the spino-sternal articulation. The first
movement gives increase of the back-to-front diameter, the other
of the side-to-side. Now, although in a general sense this de-
scription is essentially true, yet when one comes to study the
costal movements in the living and the arrangement of parts in
the dead, it is found to afford a very imperfect explanation of
_what is seen. The ribs vary in size, shape, inclination, articula-

7

tion, and action from the first to the twelfth; to describe the
action and movement of each would cause the student to be lost
in detail. It is enough, in the writer’s opinion, to-recognise that
in the thorax there are two parts which are functionally inde-
pendent ; these are (1) the upper mechanism connected with the
expansion of the upper lobe of the lung (the part above the great
fissure), consisting of the second, third, fourth, and fifth ribs, and
their attached muscles; and (2) the lower mechanism, consisting
of the sixth, seventh, eighth, ninth, and tenth ribs, and their
attached muscles, designed for the expansion of the lower lobe.
In this lower mechanism the diaphragm is the dominating part.
The lower set of ribs is specially adapted to act with the diaphragm ;
they are an intrinsic part of the diaphragmatic mechanism. The
floating ribs, the eleventh and twelfth, and in 40 per cent. of bodies
the tenth also belongs to this group, are, from a functional point —
of view, essentially a part of the abdominal wall; their articula-
tions and movements are peculiar. The peculiar shape and action
of the first rib has already been described. In the writer’s opinion
it is necessary, for a full analysis of the respiratory movements
in health and in disease, to distinguish four parts in the costal
series—(1) The first rib, part of the thoracic operculum ; (2) the
upper costal series (second to fifth); (3) the lower costal |
series (sixth to tenth), an intrinsic part of the diaphragmatic
mechanism; (4) the floating series, functionally a part of the
_ abdominal wall..

902 THE MECHANISM OF

THe RESPIRATORY MOVEMENTS OF THE LOWER CosTAL SERIES

The muscles and movements of the lower series are totally
different from those of the upper. The dominating muscle is the
diaphragm ; the other muscles are so arranged in their attach-
ments as to act either as synergic muscles (the ilio-costalis, the
external intercostals, the interchondrals) or as antagonists (the
external oblique, the internal oblique, the internal intercostals,
and the transversalis). The ribs of the lower series are articulated _
to the spinal column in such a manner that the lateral and anterior
part of each moves outwards more than the one above it during
inspiration. The spinal part of each (50 to 70 mm. in length)—
the part to which the erector spine is attached—rotates and
actually moves forwards (sternal-wards) during inspiration. The —

4
*

RESPIRATION IN MAN 203

tubercle of the rib glides downwards and forwards on the flat
upper facets on the transverse processes. The axis of the move-
ment in the lower set does not correspond to the neck of the rib ;
it corresponds to its spinal segment and is determined by the action
of the muscles rather than by the shape of the articulations and
ligaments. Anteriorly the diaphragmatic set of ribs is inserted
to the lower end of the sternum by the strong peculiar complex
formed by the costal cartilages of the sixth, seventh, eighth, and
ninth ribs. As the diaphragm and external intercostals elevate
the lower costal series, they also raise the sternum upwards through
the cartilage complex. The ilio-costalis, rising from the iliac crest,
steadies the spinal segments of the ribs, or during an energetic

inspiration actually draws them downwards. The result of a

movement of the lower ribs—or better, of the action of the
diaphragmatic mechanism—is to increase the transverse and back-
to-front diameter of the lower thorax and the vertical diameter of
the whole cavity.

- RESPIRATORY MOVEMENTS OF THE FLoatiInG Riss

As already mentioned, the eleventh and twelfth ribs are
functionally parts of the belly wall. Sibson observed that the
tenth and eleventh intercostal spaces widen during inspiration,
and diminish during expiration, an observation which the writer
has frequently verified. The opposite is true of the other spaces.
The twelfth rib is not only controlled by the quadratus lumborum
and erector spine muscles, but also by a strong and constant
ligamentous membrane, the function of which has been entirely
overlooked. This membrane, really an extension of the middle
layer of the lumbar fascia, anchors the lower border of the twelfth
rib to the transverse processes of the first and second lumbar ver-
tebree ; it is continued up between the spinal parts of the lower
five ribs. Thus the lower five ribs at and near their angles are

_ bound to the spinal column in such a way as to strictly limit the

upward movement of the spinal segments of the ribs. On the
other hand, the lateral and anterior parts of the ribs are not so
limited ; the whole arrangement is designed to secure the move-
ments of the lower ribs round an axis, not corresponding to their

necks, but to their spinal segments, the parts to sso the erector
aa is attached.

™

204 THE MECHANISM OF

RESPIRATORY MOVEMENTS OF THE Upper RIBS

The upper ribs differ from the lower set (1) in their muscu-
lature ; (2) in their articulation and ligaments; (3) in their shape
and arrangement; (4) in their movements. Their movement is
designed for the expansion of that part of the lung which lies
above the great fissure. The musculature of these ribs is the inter-
costal and interchondral. The first rib and its muscles provide a
fulcrum towards which the upper set of ribs may be raised, while
the lower set of ribs, fixed by the abdominal musculature, affords
a fixed base towards which they may be depressed during expira-
tion. Now the spaces between the ribs of the upper set are
peculiarly wide on the anterior and lateral aspect of the chest—
the area covered by the pectoral muscles and the upper part of
the serratus magnus. It is in these spaces that most observations
on the action of the intercostal muscles have been made. Duchenne
noted that during life the musculature of these spaces was tense
during inspiration and lax during expiration in the living, and
inferred that both external and internal intercostals were in action
during inspiration, and out of action during expiration. That was
also Haller’s opinion. Rutherford and many others also drew
that inference from experiments on the articulated thorax. Sibson,
who was an accurate observer, also agreed that the internal inter-
costals of the subpectoral region of the chest are inspiratory in
function. Both internal and external muscles have the power
of diminishing the intercostal spaces, and may therefore act as
inspiratory or expiratory muscles according to whether they act
from the first rib or from the sixth. One must receive with
caution the inferences drawn from experiments which involve a
wide disturbance of the circulatory and reflex mechanisms—such
as those of Martin and Hartwell. They found the interchondral
as well asthe internal intercostal muscles were expiratory, a con-
clusion altogether at variance with the fact that these cartilages
are elevated during inspiration. In other parts of the thorax,
with the exception of the anterior and lateral aspect of the upper
part of the thorax, the internal intercostals are normally a
muscles.

The spinal articulations of the ribs of the upper set differ from
those of the lower set. The articulation on the tubercle is a con-

ris

RESPIRATION IN MAN 205

vex ovoid facet, and fits into a corresponding hollow facet on the
transverse process. unlike the flat facets of the lower rib. Each
transverse process from above downwards is tilted a little more
backwards than the one above, so that the angle at which the ribs
are set to the spine increases as one passes down the series. The
double articulation of each rib to the spine by its head and by its
tubercle prevents any rotation of the rib round a sterno-spinal axis.
There can be no “ bucket-handle”” movement. The axis on which
the upper ribs move corresponds to their necks. The only part of
the erector spine which can influence their movement is the acces-
sorius. The series of slips included in this muscle rises from the
lower set and is inserted into the upper set of ribs. It is
physically possible for this muscle to act on the upper set during
expiration. The muscles named levatores costarum increase in
size from first to twelfth, being thus largest to the rib which is in
least need of elevation ; they are so inserted to the ribs as to be
unable to influence the movements of the ribs; they are not con-
cerned in respiration but in lateral movements of the spine.

One can see from the shape of the upper ribs that their
mechanism is totally different to the lower set. The ribs of the
upper set have a concave upper margin, the lower convex; the
upper ribs are shaped like the blade of a sickle; each successive
rib from second to fifth making a greater lateral and forward
sweep than the rib above it. The ribs of the lower set form a
vertical series, the one situated vertically above the other. The
upper set is designed for the expansion of the conical upper lobe,
the lower set for the expansion of the lower lobe which is a segment
of a cylinder.

Recently Dally has again directed attention to extension of
the spine as a normal means of expanding the thorax. He has
studied the spinal movements by means of the othodiascope.
Hutchinson and Hasse have each demonstrated a normal in-
spiratory extension of the spine. Extension of the spine causes
an increase in all three diameters of the thorax.

It would carry this article to an undue length were the writer
to deal fully with other matters connected with the mechanism
of respiration, such as its influence on the circulation (see Wencke-

bach and T. Lewis); with the changes which set in soon after
adult life and gradually increase until.old age (see Mehnert). He
feels he has scarcely done justice in his review to the articles of

~~
*

206 THE MECHANISM OF

du Bois Raymond, Boruttau, and Hart, the last named having
compiled a most useful summary of German literature treating of
the relationship of phthisis to the mechanism of respiration.

BIBLIOGRAPHY

Abrams, Lancet, Oct. 10, 1903, p. 1052.

Du Bois Reymond, Mechanik der Atmung. Ergebnesse der Physiol. Bd.1
1902, Abth. Bio-physik., p. 277.

H. Boruttau, Die Atembegwegungen und ihre Innervation. Handbuch
der Physiol. der Menschen, Nagel, Braunschweig, 1905, Bd. 1, Abth. 1,
pp. 1-56.

Braune, Der Sternelwinkel, Angulus Ludovici, in Anatomische und Klin-
ische Beziehung. Archiv. fur Anat. und Physiol, Anat. Abth. 1888, p. 306.

Colbeck and Pritchard, An Explanation of the Vulnerability of the Apices
in Tuberculosis of the Lungs. Lancet, June 8, 1901. :;

&. H. Colbeck, The Phenomena of Tidal Percussion at the Apices of the
Lungs. Practitioner, March 1903.

J. F. H. Dally, A Contribution to the Study of the Mechanism of Respira-
tion. Proc. Roy. Soc., Feb. 6, 1908 ; Lancet, June 27, 1903, p. 1802.

Duchenne, Physiologie des Movements, Paris, 1867.

Elsberg, Zentralbl. fur Chirur., No. 10, 1908.

W. A. Freund, Der Zusammenhang gewisses Lungen Krankenheiten mit
Primaren Rippen Knorpelanomalien Erlanger, 1859, p. 127. (For references
to Freund’s later papers see Hart.)

K. Gregor, Die Entwickelung der Atemmechanik in Kindesalter. Anat.
Anz., Bd. xxii., p. 119, 1902.

C. Hart, Die Mechanische Disposition der Lungen spitzen zur tuberku-
losen Phthise, Stuttgart, 1906, p. 267.

C. Hasse, Die Formen des menschlichen Korpers und die Wort viccalae
rungen bei der Atmung, Jena, 1888—90, parts i—ii.

C. Hasse, Ueber die Atembemegungen des Menschlichen Korpers. Arch.
f, Anat. u. Physiologie, 1901 and 1903.

W. R. Huggard, Brit. Med. Journ., Oct. 14, 1905.

J. Hutchinson, article on “‘ Thorax.” Todd’s Cyclopedia of Anatomy and
Physiology, vol. iv., 1852.

E. Lloyd Jones, The Physical Examination of the Upper Regions of the
Chest. Brit. Med. Journ., Oct. 24, 1903.

A, Keith, A Variation which occurs in the Manubrium Sterni of Higher
Primates. Journ. Anat. and Phsyiol., vol. xxx., 1896,

A. Keith, A Contribution to the Mechanism of Respirationin Man, Proe-
Anat. Soc. of Gréat Brit. and Ir., May 1903.

A. Keith, Why does Phthisis attack the Apex of the Lung? London |
Hospital Gazette, Nov. 1903.

A. Keith, The Nature and Anatomy of Enteroptosis. eee Marchi a
1903, p. 634.

—-

*

RESPIRATION IN MAN 207

_ &, T. Mackenzie, The Relationship of the Thoracic Type to Lung Capacity.
- Montreal Medical Journ., vol. xxxiii., 1904, p. 237.

_ Martin and Hartwell, On the Action of the Intercostal Muscles. Journ.
of Physiol., vol. ii., 1879, p. 24.

EE, Mehnert, Ueber topographische Altersveranderungen des Atmungs-
apparates, Jena, 1901.

Meltzer, The Respiratory Changes of the Intrathoracic Pressure. Journ.
of Physiol., vol. xiii., 1892.

H, von Meyer, Der Mechanismus der Rippen. Archiv. fur Anat. und
Entwickel, Leipzic, 1885, p. 253.

A. Moso, Action des centres spinaun sur la Toncite des Muscles Respi-
rateurs, Archiv. Ital. de Biol., t. xli., 1904, p. 111; also t. vii. p. 93.

A. Mosso, Le Movements ‘yeapiratoires du Thorax et du diaphragme.
Arch. Ital. de Biol., t. xl., 1903, p. 43.

_ A. Oppel, Lehrbuch der mikroscopischen Anatomie der Wirbeltiere: part
vi., Atmungs Appar., Jena, 1905,

W. Pasteur, Massive Collapse of the Lung. Lancet, Nov. 7, 1508, p. 1351.

Sir R. Douglas Powell, On some Effects of Lung Elasticity in Health and
Disease. Medico-Chir. Soc., vol. lix., 1876, p. 165.

A. Ransome, Observations in the Movement of the Chest. Journ. of Anat
and|Physiol., vol. iv., 1870, p. 140.

Clive Riviere, Lancet, June 8, 1907, p. 1603.

Rothschild, Ueber die physiologische und pathologische Bedeutung des
Sternelwinkels, XVII. Kongr. f. inn. Med., Karlsbad, 1899. (Hart gives full
references to his later papers.)

Rutherford, Note on the Action of the Intercostal Muscles. Journ. of Anat.
and Physiol., vol. x., 1876, p. 608.

Sewall aud Pollard, On the Relationship of Diaphragmatic and Costal
Respiration to Phonation. Journ. of-Physiol., vol. xi., 1890, p. 159.

F. Sibson, On the Mechanism of lespiration. Philosophical Trans., vol.
exxxvi., 1846, p. 501.

N. Ph. Tendeloo, Studien ueber die Ursachen der Lungen Krankenheiten,
Wiesbaden, 1902, p. 480.

K. F. Wenckebach, Ueber Pathologische Beziehungen Zwischen Atmung
und Kneislauf beim Menschen. “Sammlung klinischer Vortrage, Neue Folge,
Leipzig, 1907.

THE PHYSIOLOGY OF MUSCULAR WORK

By M. 8. PEMBREY

CHAPTER I
INTRODUCTION

ALTHOUGH muscular work hes always been one of the most im-
portant factors in every-day life, it has not received sufficient
attention from medical men. It has been the subject of much

writing, numerous casual observations, but few scientific investi-

gations. The practical importance of a knowledge of the influence
of muscular work was never greater than it is at the present time.
The migration from the land to the towns has deprived the youth
of this country of many of the opportunities for healthy muscular
exercise which their forefathers possessed. The increasing use
of machinery in all occupations has reduced the demand for
healthy muscular labour, and has thrown an extra strain upon the
nervous system of the working man. The much-vaunted advances
of medicine and surgery have prevented oftentimes the beneficent
action of the law of the survival of the fit, and a morbid sentimen-
tality under the guise of charity has pampered the degenerates of the
country. The bad must be taken with the good, but this necessity
does not make any thinking man satisfied with the conditions of
modern civilisation. Its defects are well recognised, and for this
reason the outlook is hopeful. The fear of a physical deterioration of
the race found expression recently in the appointment of a depart-
mental committee of inquiry, and serves at the present time as a
strong argument in the hands of the advocates of compulsory
military service. If degeneration is to be prevented, the public
must recognise more fully the vanity of luxury and the benefits
of healthy muscular exercise, whether it be as work or play, and

must insist that the population is not weakened by immoral efforts _

to diminish the birth-rate and a healthy struggle for existence.
Physiologists have often neglected the question of muscular

* work or have devoted a vast amount of time and ingenuity to
208

THE PHYSIOLOGY OF MUSCULAR WORK — 209

experiments upon the isolated muscles of frogs. This has been
reflected in the teaching and training of medical students. The
underlying idea of the supporters of the school of muscle and
nerve appears to be or to have been that a thorough investigation
of the properties of two tissues would solve the problem of vital
activity. The mystery is greater than ever it was. The day of
that school of physiology is passing. A reaction set in some
years ago, has not waned, but has steadily gained in strength.
. Some extremists would maintain that the investigation of isolated
muscles and nerves is strictly not physiology ; that a muscle and
nerve under such abnormal conditions is pathological and patho-
logical to a degree which does not obtain under the ordinary
- conditions of life. It cannot, however, be denied that such ex-
perimental work has its value, for all knowledge is useful if it be
properly appraised. Muscle and nerve are not units of life; the
unit is the living organism. Muscular activity under natural
conditions is exhibited only by the organism, and under such
conditions it should be studied.

Athletes and the trainers of men and animals for sport have
done much for the practical study of the physiology of muscular
work. The practice of training is even at the present time ahead
of the theory, and each year physiological investigations show the
value of the methods introduced by athletes. Experience has
been the guide of athletes, and experience is the result of nume-
rous physiological experiments upon a large number of men. The »
diversity and gradation of the muscular exercise involved in the
numerous forms of sport render it suitable for all men, young and
old, strong and weak. In these and many other respects sport is
far superior to physical drill and gymnastic exercises, and as such

. deserves even more recognition and study than it already receives.
: The main purpose of this article is the physiology of muscular
work in man. It will be necessary, however, to glance at some
of the elementary facts concerning the structure and properties
of muscle considered as a tissue.

Tue Structure oF Muscie

There are many interesting differences in the naked eye and
microscopical structure of muscle, and these must be considered in
relation to the various functions of the different kinds of muscular
te)

210 THE PHYSIOLOGY OF MUSCULAR WORK

tissue. In muscle the power of contraction, which is present in
the primitive cell, has been especially developed in the process of
division of labour and differentiation of structure. Three kinds
of muscle are recognised—voluntary, cardiac, and involuntary.
Their minute structure, which has given rise to much con-
troversy, is strictly a question of anatomy, and will not be
discussed here. There are not only differences in the structure,
composition, and properties of voluntary muscles in different
animals, but also in the same animal. The best known example
is the red and the white muscle of the rabbit (+). Simple inspec-
tion of the muscles of a rabbit directly its skin is removed de-
tects a marked contrast in the colour of the different muscles ;
the masseters and some of the muscles of the hind limbs, such as
the soleus and semi-membranosus, are red in colour, but most of
them are pale. This difference is not due solely to variations in -
the vascular supply, for even after the blood has been removed a
contrast remains. The red muscle fibre contains hemoglobin and
myohematin within its substance, and these pigments are pro-
bably of some importance in the process of internal respiration.
The capillary blood vessels have dilatations, which are not pre-
sent in the case of the pale muscles. The red fibres are thin with
nuclei in their substance as well as under the sarcolemma, and the
transverse striation is less regular. Functional differences can be
easily demonstrated. The red muscle contracts and relaxes slowly,
in marked contrast to the rapid wave of contraction in white
muscle ; red muscle is more easily tetanised, and does not pass into
rigor mortis so rapidly.

THE PHYSICAL AND CHEMICAL PROPERTIES OF MUSCLE

One of the most important characteristics of muscle is its
elasticity. A muscle fibre regains its original length after it has
been stretched within certain limits; it possesses perfect elas-
ticity and conforms to Hooke’s law; the successive increments in
length produced by equal increments of weight are equal. It is
only when the muscle has been extended beyond the limits to
which it is exposed in the living body that its perfect elasticity
is impaired (*). ie

In the normal condition muscles are stretched between their
points of attachment and by the action of antagonistic muscles ;

THE PHYSIOLOGY OF MUSCULAR WORK 2l1

if a muscle be cut across its ends retract in the wound. The
practical importance of this elasticity is found in the more prompt
performance of work; the muscles are taut and have not to take in
slack when they begin to contract. The extensibility of a muscle
is greater during contraction than in the condition of rest. This
is a further safeguard to the muscle in any sudden or vigorous
contraction against a great resistance; the shock and strain are
lessened and rupture of the muscle is prevented. It is more
common to find bones fractured than muscles ruptured by violent
contraction. Later it will be shown that in addition to this elas-
ticity the muscles have a condition of tone or tonic contraction,
which increases their efficiency in the performance of work.

Muscle consists of 25 per cent. of solids and 75 per cent. of
water ; twenty parts of the solids are proteins, and the remaining
five parts are extractives and inorganic salts. From the muscle
can be expressed a viscid alkaline juice which soon becomes
acid and clots. The chief constituents of this muscle plasma
are the proteins investigated and named by Halliburton (*) para-
myosinogen and myosinogen; they correspond respectively to
the myosin and myogen of Von Fiirth(*). These proteins in most
respects resemble the globulins; para-myosinogen is coagulated
by heat at 47°, myosinogen at 63°. The myosinogen gives rise to
soluble myosin in the process of clotting, and this substance, which ~
is coagulated by heat at 40°, is a normal constituent of the muscle
plasma of cold-blooded animals.

The statements made concerning the proteins of muscle plasma
may soon need revision, for in a recent preliminary communication
Mellanby (°) has maintained that there is only one protein in muscle
and that it is not a globulin.

A comparison of the protein constituents of the different kinds
of muscle brings out an interesting difference. Nucleo-protein is
most abundant in plain muscle, and least abundant in volun-
tary or striated muscle ; cardiac muscle occupies an intermediate
position in this respect. In simple cells nucleo-protein is a typical
constituent ; plain muscle is the least and voluntary muscle the
most differentiated of the three kinds of muscle; thus changes
in function and structure have been accompanied by a corre-
sponding gradation in the amount of nucleo-protein.

Another point of great interest has been discovered by a com-
_ parison of the Peeaperwiares at which the different protein con-

212 THE PHYSIOLOGY OF MUSCULAR WORK |

stituents coagulate (*). When an excised voluntary muscle of a
mammal is heated, it begins to shorten at 43°, shortens more at
47°, and again when the temperature reaches 58°. The excita-
bility of the muscle is destroyed when the shortening occurs at
47°, and this corresponds with the temperature at which para-
myosinogen is coagulated. The internal temperature of a healthy
mammal is about 36° to 37°, and it is well known that life is
endangered when owing to fever or some other cause the tem-
perature of the body rises to 44°. Birds are also warm-blooded
animals, but their internal temperature is several degrees above
that of mammals; the temperature of a sparrow is 42°, that of a
hen 41° to 43°. There must therefore be some difference in the
heat-rigor of the proteins of their muscles; experiments on this

point have proved that the coagulation of the protein does not

occur until the temperature is raised to 53°.

The temperatures at which coagulation begins are not rigidly
fixed, for prolonged heating at a lower temperature will produce
that change of state; it is necessary also to remember that the
excised muscles are devoid of a circulation of blood, and no doubt
are in a condition which is not the same chemically as the normal
muscle. These criticisms do not invalidate the practical importance
of heat-rigor in connection with the effects of hyperpyrexia and
the pathological changes which occur in muscle during prolonged
fever. It is necessary, however, to exercise care in any argument
from the part to the whole body.

The next constituents of muscle which must be considered are
the extractives ; these can be divided into two classes, the non-
nitrogenous and the nitrogenous. The former group is repre-
sented by glycogen, dextrin and sugars, inosite, fat, and lactic acid.

Glycogen or animal starch (C,H,,0,), is a polysaccharide which
appears to be intimately associated with the source of muscular
energy. The amount of glycogen which can be extracted from a
muscle varies according to its activity, and this fact will explain
the lack of agreement in the percentages found by different ob-
servers. Resting muscle contains from 0°1 to 2°5 per cent. of
glycogen. The amount not only varies in different animals, but
also in different muscles of the same animal: the more active
muscles contain less. By prolonged activity the glycogen. of the
muscles can be removed, but it disappears from the liver first ;
poisonous doses of strychnine which cause violent convulsions.

THE PHYSIOLOGY OF MUSCULAR WORK 213

bring about a loss of about 90 per cent. of the glycogen of the

muscle. During starvation glycogen disappears from the liver

sooner than from the muscles. These facts raise the question

whether glycogen is supplied to the muscles by the blood-stream

which has taken up glycogen from the liver or whether it can be
formed by the activity of the muscles themselves. There is no
conclusive evidence to show that the latter is the case, but it will
be better to defer the consideration of this point until the sources
of muscular energy are discussed in detail.

Dextrin and Sugars.—Between these bodies and glycogen there
is a close relationship. Glycogen appears to be the form in which
carbohydrate is stored up, probably in loose combination with

_ the proteins of the muscle ; dextrin, maltose, and glucose represent
the stages through which the reserve material passes on its way
to yield energy during combustion. The glycogen of an excised
muscle rapidly decreases and the sugar at the same time increases.
This conversion can be effected by the ferments which are found
in muscle; there is an amylolytic enzyme and a maltase, and by
their. action dextrin, maltose, and finally dextrose are formed.
The relation of sugar to muscular activity will be considered
later.

Inosite is found in small quantities in the muscles. It was
formerly known as muscle sugar, owing to the fact that it has the
same molecular formula (C,H,;0,) as glucose. It is not, however,
a sugar, but a crystallisable substance belonging to the aromatic
series. Nothing appears to be known of its physiological im-
portance, although it is found in other parts of the body besides
muscle.

| Fat is constantly present between the muscle fibres, but it is

| uncertain whether it is a normal constituent of muscle; there is
no definite evidence of its presence within the substance of the
fibre. Leathes (*) found that the red muscles of the rabbit contain
considerably more fat than the white muscles.

Lactic acid, paralactic or sarcolactic acid, CH,(CH.OH)COOH.
There has been a great conflict of opinion upon the question whether

the normal muscle contains lactic acid, which is always present

in dead muscle. Recently, however, the discrepancies have been
explained by Hopkins and Fletcher (*) in an important research
upon lactic acid in amphibian muscle ; by this work the knowledge

_ of the conditions under which lactic acid is formed in muscle has

9 «

214 THE PHYSIOLOGY OF MUSCULAR WORK

been greatly extended. Their results are given in the following
summary taken from their paper :—

‘Freshly excised resting muscle is found to yield very small
quantities of lactic acid, and these small amounts are possibly not
mote than can be accounted for by the unavoidable minimum of
manipulation prior to extraction.

‘« A large increase of the yield of lactic acid is found as the result
of mechanical injury, of heating, and of chemical irritation.

‘ Lactic acid is spontaneously developed under anaérobic con-
ditions in excised muscles. During the survival periods of sub-
sisting irritability, and not after, equal increments of acid arise
in equal times. After complete loss of irritability the lactic acid
yield remains stationary.

“ Fatigue due to contractions of excised muscle is accompanied
by an increase of lactic acid. The amount of acid attainable by —
severe direct stimulation is found, with notable constancy, to be
not more than about one-half of that reached in the production
of full heat-rigor, or by the action of other destructive agencies
than heat.

‘“‘In an atmosphere of oxygen there is no survival development
of lactic acid for long periods after excision.

“ From a fatigued muscle, placed in oxygen, there is a disappear-
ance of lactic acid already formed.

“‘ This disappearance of lactic acid due to oxygen does not occur,
or is masked, at supra-physiological temperatures. It is not found
in muscle which has suffered mechanical injury; one essential
condition for this effect of oxygen appears to be the maintenance
of the normal architecture of the muscle.

‘The amount of lactic acid produced in full heat-rigor is con-
stant for similar muscles. This ‘acid maximum’ of heat-rigor is
not affected by a previous appearance within the excised muscle
of lactic acid due to fatigue, or by a previous disappearance of
acid in the presence of oxygen, or by alternate appearances and
disappearances several times repeated.”

It will be necessary later to consider this work in its bearing
upon the effects of muscular activity, upon hyperpneea and muscle
soreness; at the present time only the chemical characteristics
of muscle have to be discussed.

The nitrogenous extractives of muscle form a large group; the
chief ones are creatin, carnic acid, inosinic acid, carnosin and purin

THE PHYSIOLOGY OF MUSCULAR WORK 215

bodies. It is impossible to give a satisfactory account of their
significance in the physiology of muscular work, but an attempt
will be made to pick out the observations of most interest.

Creatin is a substance which crystallises out when an aqueous
extract of meat is allowed to evaporate. It has the formula
C,H,N,0.. E. Mellanby(°) has found that it is present in
different amounts in the muscles of various animals; as a general
rule there is a greater quantity in the muscles of animals in an
ascending scale of development from the cold-blooded to the
warm-blooded. This is illustrated by the following table :-—

Lamprey . . ‘25 percent. Hedgehog (winter) . . °2 per cent.
Skate. ee a5 ‘ (summer) oh eee
Cod . : 3 4 Rats (two months old) . 3 __s,,
Frogs ‘ 2 EG: Ps Bullock . ; i 6. Bi gs
Fowl , Par) eae Pig. c : : es Seer
Guinea pig . ‘32, Rabbits . : : ee

A further interesting difference was discovered by an analysis
of the muscles of similar animals during several stages of de-
velopment.

Rabbits (foetal, 21 days) . ; : : . a trace.
» ‘@daysold . : ‘ : ; . ‘191 per cent.
es: aes a a een... apes
of AS yl ee ee. ae
410. 2 ne ee ms lee
» > ar oe en ee
a a ee ee ae na
gs fs mee Od oe en ca TRE
» adult a ra OF ee
Chick embryo, before 12thday. . . . .~ no trace.
" » Weight 671 grms. 12th day . : . a trace,
s Ps a 119° 14th, : . 38 mgre. total.
! ” ” » %W3 ,, 16th » °¢ . . 66 ”
i. . =. $60. 10th eo S18 .
ee ee ns |) ae
Chick, weight 36-0 grms. 1 ig) after re but
no food taken . P . 230 3

In the embryo chick creatin is absent at a stage of develop-
ment when muscle is present ; in hedgehogs the quantity of
creatin in the muscles remains constant throughout the year,
notwithstanding the great differences in the metabolism of these
animals during the periods of hibernation and activity.

216 THE PHYSIOLOGY OF MUSCULAR WORK

Creatin is absent from invertebrate muscle, although morpho-
logically and physiologically the cross striated muscle of these
animals is identical with that of vertebrates. The closely related
substance creatinin, C,H,N,O, is not present in muscle, and is
not formed from creatin during prolonged work. Creatin has
apparently no influence on muscular contraction or the passage of
a nervous impulse into muscle. From a consideration of these and
other facts, Mellanby suggests that creatinin is formed into creatin
and-stored in the muscle, and that the development of the liver
in the vertebrates may account for the presence of creatin in their
muscles; the gland of the mid-gut of invertebrates, although it
has been called a liver by some biologists, has no morphological or
physiological connection with the liver of vertebrates. The urine
of young children is almost free from creatinin, and chicks do not
excrete creatinin until about a week after hatching, by which time —
their muscles are saturated with creatin.

The other nitrogenous extractives found in muscle are carnic
acid, C,,H,,N,O,, combined with phosphorus to form phospho-
carnic acid ; carnosin, C,H,,N,O,; iosinic acid, C,H, .N,PO.5
small quantities of wrea, CO(NH,).; and of the following purine
bodies—hypoxanthine or oxypurine, C,H,N,O ; xanthine or dioxy-
purine, C,H,N,O, ; and uric acid or trioxypurine, C;H,N,O;. The
significance of these substances in the metabolism of muscle is
unknown.

THE INORGANIC SALTS OF MUSCLE

There are considerable variations in the quantity of the in-
organic salts which are present in the muscles of different animals,
but in all the samples analysed potassium and phosphorus are the
most abundant constituents. The following results expressed in
parts per 1000 were obtained by Bunge (1°) :—

Lean Beef. Fat Beef.

KO. . . » « #@5d 4°160
NaO. « « «© Of 0811
a 0-072
MgO. «. iv oe » hee 0381
BOD. \ oho cee cn hus Rae »>
2 a eee eee 4580
Gos CO Se eee
BOR \: Nb 0:010

s ; ‘ , ‘ otras 2°211 -

THE PHYSIOLOGY OF MUSCULAR WORK 217

In the above table the sulphur is represented in two divisions ;
the first gives the sulphate which can be extracted by water, and
the second the total sulphur after incineration. The difference
is due to the large quantity of sulphur which is set free by the
destruction of the proteins of the muscle.

Interesting observations upon the distribution of potassium
in muscle have been made by Macallum ("'), who precipitated the
potassium as the hexanitrite of cobalt, sodium, and potassium. In
striated muscle there is a condensation of the potassium in the
dim bands, the rest of the fibre remaining free from the precipitate ;
in involuntary muscle it is smaller in amount and is diffused
throughout the cytoplasm, and in cardiac muscle it is distributed
-as in voluntary muscle. Macallum suggests that the potassium
is associated with the rapidity of contraction.

THE PIGMENT OF MUSCLE

The exact nature of the pigment, which is present in muscle
after the blood has been washed out, has given rise to much con-
troversy. MacMunn (*) found associated with hemoglobin in the
muscles a pigment which gave a different spectrum ; this he named
myohematin. He observed it in a compressed fresh muscle when
it was held before the slit of a spectroscope, and on account of its
capacity for oxidation and reduction he considered it to be a
respiratory pigment. It was maintained on the other hand by
Hoppe Seyler and his pupils that the pigment was either hemo-
globin or a derivative produced by putrefaction. After the lapse
of some years the subject has been reinvestigated by Mérner (?%),
who confirms MacMunn’s view, and suggests that the pigment
differs from hemoglobin in the combination of its hematin with
some other protein or in a different linkage of the components.

THE FERMENTS OF MUSCLE

Modern investigations have demonstrated the great importance
of unorganised ferments in physiological: processes (1*) ; the living
cell may be compared to an organised ferment which produces
unorganised ferments or enzymes. In voluntary muscles there
have been found amylolytic, glycolytic, and peptic enzymes, or in
_ other words, ferments which act upon glucose, glycogen, and protein

218 THE PHYSIOLOGY OF MUSCULAR WORK

respectively ; there are also present maltase and an oxidising
ferment, or oxydase. These ferments doubtless play important
parts in the exchange of material in the muscle, for in addition to
their definite action there is the probability of a reversible action ;
the breaking down process may, according to the condition of
the tissue, be replaced by the building up or synthetic process.

CHAPTER II

Facts concerning the structure, and the physical, chemical, and
physiological properties of muscle, have been given as an intro-
duction to the physiology of muscular work. It is now necessary

to study the effects of muscular exercise or work upon the living

organism, especially man.

The origin of muscular activity we cannot trace, nor can we
think of its beginning in the offspring of any animal. Muscular
activity is a specialised form of protoplasmic movement, and the
capacity for such movement is an attribute of the minute male
and female cells from the union of which the offspring arises.
There has been a continuity of life from parent to offspring through
countless generations, and this carries with it the potentiality of
muscular movement. Heredity has a far-reaching influence upon
muscular development and activity; even at birth the power of
co-ordination possessed by some animals is remarkable. A guinea-
pig is born with its eyes open and its body covered with fur, and it
is able to run about: a calf within a few minutes of first seeing the
light is able to walk and seeks its mother’s teats. These young
animals do not learn to walk, but learn by practice to make perfect
the power of walking which they possess at birth. A marked
contrast is seen in the newly born rabbit, rat, and mouse; they
are blind, naked, and helpless. A study of birds reveals a similar
difference. Within an hour or two of hatching the chick is able
to run about and peck up its food ; the pigeon, on the other hand,
is for several days blind, naked, and helpless. The maturity or
immaturity of different classes of animals at birth is related to the
natural habits of the race and to adaptation.

The condition of the newly born child is intermediate between —

the extreme examples just given; its muscular development and
power of co-ordination are considerable, and are especially seen

i
‘“

THE PHYSIOLOGY OF MUSCULAR WORK — 219

in its capacity to grasp with the hands and feet. Most interesting
observations have been made upon this subject (15), which affords
strong support for the Darwinian theory of evolution. Infants
at the very beginning of their separate existence possess a remark-
ably strong grip; they can hang by their hands from a horizontal
bar and support their own weight, and the strongest may maintain
their position for two minutes. Most adults would find it difficult
to support themselves in this way for a quarter of the time. Infants
possess also a power of grasping with the foot; the great toe is
abducted and the foot is held more in the position of a hand. This
power is gradually lost as the child grows up, and is only found
greatly developed in the adult in those rare cases of congenital
absence of the arms and hands. These prodigies may be seen at
fairs exhibiting their skill in using their feet for all the purposes
for which an ordinary man uses his hands.

For these characteristics of the infant there appears to be
no adequate explanation except the one suggested by Dr. Louis
Robinson. He considers that they are examples of atavism ; that
the infant of primitive man was carried in a manner similar to that
seen in apes, the offspring clinging to the parent by grasping with
its hands and feet the hair under the arms and over the pubes.
Grasping their parents’ hair is well known to afford infants their
earliest form of amusement. Dr. Robinson has also pointed out
that his view would offer an explanation of the great development
of hair over the pubes and in the axille at the time of puberty.

It is well known that the foetus often makes active movements
in the uterus; these movements are known as “ quickening with
child,” and by one of those subtilties in which the legal mind
delights have acquired some importance, for they entitle any preg-
nant woman who is condemned to death to at least a temporary
reprieve. In many cases, however, no active movements may be
detected even in the last days of pregnancy.

There is another striking example of muscular power and co-
ordination in the infant. Within a few seconds of its birth it
draws its first breath, and continues to ventilate its lungs by
alternate contraction and relaxation of its respiratory muscles,
although up to this time its respiration has been entirely carried
out by the placenta. Ahlfeld (!*) maintains that this activity of
_ the respiratory muscles is not suddenly assumed at birth, but

_ that slight respiratory movements can be detected in the fcetus

220 THE PHYSIOLOGY OF MUSCULAR WORK

inside its mother’s womb during the last months of pregnancy.
These movements he has studied both by palpation and by a
graphic record; they resemble the respiratory movements of a
newly born infant in their irregular rhythm and in periods of
waxing and waning. The criticism that such respiratory move-
ments would draw the amniotic fluid into the lungs is not a serious
one, for the movements are slight, and even if the fluid were drawn
_ further than the naso-pharynx it would be rapidly absorbed, and
being sterile and isotonic, would not injure the foetus. It would
appear, therefore, that all the muscles of the body are exercised
during foetal life for the work which they have to perform after
birth. It is impossible to say that muscular contraction appears
at any definite time.

Great advances have been made in the study of muscular
movements in man and animals since the introduction of in- |
stantaneous photography. Before that time too much stress had
been laid upon the anatomical aspect of muscular movements.
It is impossible to analyse movement in the living by an examina-
tion of the points of origin and insertion of the different muscles
acting upon the joints of dead subjects. Such imperfect know-
ledge could only be partly corrected by careful observation of
the natural movements; for the eye is not able to follow the
real sequence of events; the impression given to the observer is a
composite one of several movements. It is owing to this fact that
many instantaneous photographs of men and animals in motion
do not appear true to nature and are inartistic. The credit of
first analysing movements by relays of instantaneous photographs
is due to Muybridge; his work has been greatly extended by
Marey and others. If such photographs are seen in rapid succs-
sion the observer receives the impression that the objects are in
motion ; this is due to the persistence of visual impressions, and
is the principle involved in the bioscope.

Another method introduced for the analysis of movements is
the graphic one developed by Marey. It may be explained as an
extension of the simple method of footprints. A man skilled in
woodcraft can tell the nature and pace of an animal from its
spoor or footprints, and by the examination of the fossils of such
impressions geologists have been able to study the movements of
animals which became extinct before the time of man.

It would be outside the scope of this article to pursue this

THE PHYSIOLOGY OF MUSCULAR WORK 221

subject further, but it may not be amiss to point out how efficiently
movements are carried out; the means are adapted to the end in
view, and by practice the man or animal unconsciously learns to
perform the movement in the most economical manner. “ Practice
makes perfect”; natural movements cause less fatigue than con-
ventional ones, and herein lies the explanation of the fact that
the pace and style of one man may be quite unsuited for another.
An adult experiences more fatigue when he adjusts his pace to
that of a child than when ‘he walks the same distance at his usual
speed. A child learns to crawl, walk and run, even if it receives
no assistance from its mother ; healthy exercise is all that is needed,
and the experience thus obtained is a far better guide than any
system of teaching or drill. A movement which is suitable for one
individual is unsuitable for another; some men have long legs,
some short legs, and each walks most efficiently at his own pace.
This is not sufficiently recognised by many trainers, but the re-
cords of many a contest on land and water show that style’is a
personal factor which can never be rigidly fixed.

Muscular work is not a localised expenditure of energy; all
parts of the body are involved in a greater or smaller degree ; it is
useless to attempt to simplify the analysis of the process by experi-
ments upon the isolated muscle. Such a preparation is artificial,
and the issue is confounded. A recognition of the complexity
of the changes involved in muscular work enables us to under-
stand how far reaching are the effects which can be produced by
exercise. Anatomical changes are produced in the body; not
only do the muscles become larger, but the pull exerted by them
causes changes in the size and shape of the bones. In certain
cases such great changes are produced by the repeated contrac-
tions of certain groups of muscles that the occupation of a man
may be determined by an examination of his skeleton (1).

- The law of the conservation of energy shows that without an
adequate supply of energy in the form of food there can be no
transformation into the energy of muscular work. The food must
be adjusted to the work obtained from a man or beast, a truth
which is constantly neglected with disastrous results. A man or
horse works best when he is well fed, and feeds best when he is
well worked. This is recognised by those who have extracted the
_ greatest and most prolonged efforts from each. Napoleon is
_ credited with the saying that “a soldier fights on his belly.” A

~

‘ale

222 THE PHYSIOLOGY OF MUSCULAR WORK

man who takes enough active exercise does not overfeed and be-
come corpulent, even if the supply of food is unlimited; his
appetite is the expression of the needs of his body, and when these
are satisfied the desire for food ceases.

The digestion and assimilation of the food involve the activity
of the alimentary canal and its various glands. Muscular work
produces hunger, and “ hunger is the best sauce ” ; healthy exercise
enables a man to enjoy and digest food which otherwise he could
not eat. Pity for the labouring poor on account of the plainness
of their fare is misplaced.

The muscles are thrown into activity in response to various
impulses, and in this way the whole of the nervous system, in-
cluding the special senses, is influenced by muscular work. It is
not a question of the discharge of motor impulses alone, but a
general effect upon the whole system, so that a man overwrought |
by sedentary mental work often finds the best restorative in
muscular exercise.

The respiratory system is thrown into greater activity to supply
the increasing demand for the intake of oxygen and the discharge
of carbon dioxide. The heart and the vaso-motor system must
likewise respond with increased activity to maintain an adequate
supply of blood and to adjust the flow to the different organs
according to their relative needs. The sweat glands are stimu-
lated by the increased heat of the body, and the kidneys will
be influenced by the waste products of muscular activity and
digestion.

It may be said that it is unnecessary to lay so much stress upon
the value of muscular activity. It is not so. The benefits of
muscular work cannot be overestimated. It is a physiological
need of a primitive kind, and cannot be eliminated by civilisation.
If all men were well worked and well fed many of the great social
problems of the present day would be solved. Physiological
truths might be carried with advantage into the consideration of
social questions. Would there be any danger to the race if those
who did not work were not well fed? Do not those who have
not to earn their bread show their recognition of the virtue of
muscular work by their devotion to manly sports ?

Muscular exercise is a necessary condition of a healthy exist-
ence; it is difficult to find the man who has been injured by
muscular work, it is easy to procure many who have. been ruined

]
:

THE PHYSIOLOGY OF MUSCULAR WORK — 223

by the lack of it. The child or young animal which is not active

for the pure love of activity is unwell. The belief that progress

lies chiefly in mental training is less rampant than formerly. The

| compulsory education of young children has increased the in-

fectious diseases to which they are liable, has stunted the growth
of their originality as well as their bodies, and has in many cases
produced that mental instability which has revealed itself at a
later stage of life in crime, insanity, or suicide. The sup-
pression of the instinct to play has gone so far that it has become
necessary to found societies for the purpose of teaching children
how to play. Even the believers in compulsory education of young
children have taken alarm, and think they can undo the harm by
compulsory systems of monotonous drill, unnatural postures, and
breathing exercises. The irony of it is that this kind of physical
training is said to be based upon the teachings of physiology. It is
a false physiology which does not recognise that natural exercise
is the best, that instincts in healthy children ought not to be unduly.
suppressed, and that heredity is more potent than systems of
education.

Types or MuscuLar EXERCISE

Notwithstanding the numerous gradations of muscular exercise
between the slightest and the most severe and prolonged exertion,
it is convenient to recognise three types (78) : (1) Exercises of speed
are those in which each individual effort is produced rapidly, but
the maximum contraction of any single skeletal muscle is not
reached ; (2) exercises of endurance are characterised, by long
and continuous efforts of moderate strength; (3) exercises of
strength are those in which the muscular exertion is very great
for a brief period, such as the lifting of a heavy weight. In these
different forms of exercise it can be shown that the effects produced

| upon the body are not the same, and a different type of physique (?*)
is found in men and animals who excel in any one of them. This
is well seen in a comparison of a runner with a navvy or of a race-
horse with a dray-horse. It is necessary to remember the im-
portance of build and heredity in this respect, and to avoid an
overestimate of training.
The general effects of muscular activity have been sufficiently
indicated ; its influence upon the different systems of the body
must now be considered.

294 THE PHYSIOLOGY OF MUSCULAR WORK

Tue Errects or EXERCISE UPON THE MuscuLaR SysTEM

The muscles of the body are in a condition of partial contraction
even during apparent rest. This so-called tone is related to the
motor and sensory nerves which supply the muscle. If these
nerves be divided and do not regenerate the muscles will first
waste or atrophy, owing to disuse, and then degenerate. De-
struction of the motor cortex of the brain will cause atrophy of
the muscles, but they do not degenerate, for through their motor
and sensory nerves they are still under the influence of the spinal
cord.

The tone of the muscles is diminished by sleep ; the observant
mother knows when her child has fallen to sleep in her arms by
the relaxation of its body. A far greater decrease in tone is pro- -
duced by the action of anesthetics; the arm of a patient drops
in a limp and lifeless manner when he is deeply anzsthetised.

From time to time the tone of the muscles varies in response
to impulses from the skin and other parts of the body; it is in-
creased by cold, diminished by heat, and herein appears to lie the
chief explanation of the effects of different climates. The body is
invigorated by a bracing atmosphere, it is depressed by a relaxing
one. The tone of the muscles is accompanied by chemical changes
and the production of heat ; in a stagnant moist and warm atmos-
phere the body does not lose heat rapidly, and therefore in the
maintenance of a constant internal temperature produces less heat
by diminishing the activity of its muscles, and as far as possible
favours the loss by a dilatation of the blood vessels of the skin.
The opposite effects are produced by a cold dry atmosphere, or even
by warm air if it be sufficiently dry and in motion. European
children afford a good instance of these influences; they will not
flourish in the hot moist districts of India. Two more examples
will be sufficient. The value of a cold bath on getting up in the
morning lies not in its cleansing properties so much as in the
bracing or stimulating effect which it has upon the whole muscular
system, including the muscles of the cutaneous arterioles. The
contrast between the walk of a man on a cold frosty morning and
on a damp warm day is known to every one who lives in this —
country.

The tonic contraction of the muscles may be so greatly increased

————

THE PHYSIOLOGY OF MUSCULAR WORK 225

that it passes into visible contractions of an involuntary nature ;
shivering thus arises, and in most cases appears to be a protective
response to the effects of cold. It is true that it may occur apart
from external cold during nervous excitement, but even in this
case observations may show that the temperature of the skin has
been lowered by a sudden and vigorous contraction of its blood
vessels.

Voluntary contraction is the shortening of the muscles pro-
duced by an effort of the will. This is only a general definition,
for movements such as walking may be performed unconsciously.
During ordinary movements the change of state is not confined to a
single muscle ; others are also involved, it may be in active contrac-
tion or in relaxation. The important researches of Sherrington *
upon reciprocal innervation have shown how the muscles can in-
fluence the activity of one another by means of their motor and
sensory nerves: the contraction of one muscle brings about the
relaxation of its antagonist. The muscle possesses in its muscle
spindles a special sensory ending which is stimulated by the
stretching produced by the contraction of its antagonistic muscle ;
in this way not only can reflex effects be produced upon the muscle,
but also upon the vaso-motor and respiratory mechanisms.

A simple movement, such as removing the finger from a key
at a given signal, may or may not, according to the individual’s
type of reaction, be preceded by a movement of the opposite kind.
This may be called the antagonistic form of reaction in contrast
to the ordinary form in which the lifting of the finger is carried
out at once (?°).

Such a movement of the finger can only be repeated about eight
to twelve times a second by the ordinary man, but a pianist by
practice and by using muscles in relays can press the keys at a
faster rate. In short, sharp, and rhythmical movements of the
fingers the rate may be as rapid as forty a second.

The nature of a voluntary contraction, whether it be a single
twitch or a spasm, requires consideration. It has been studied
in two ways, by a determination of the note of the sound produced
by the contraction of the muscle, and by graphic records. The
muscle note corresponds to forty vibrations a second, but the diffi-
culty in such a determination by the ear lies in the fact that it

1 Article Spinal Cord, ‘‘Textbook of Physiology,” edited by Schiifer, vol. ii.,

1900.

P

226 THE PHYSIOLOGY OF MUSCULAR WORK

cannot perceive a note much lower than one of that frequency.
It is probable that the muscle note really represents the overtone
corresponding to the second octave of the vibration ten a second.

The work of Horsley and Schifer (2) shows that the rate of
contraction is determined chiefly by the rate of discharge of the
nerve cells concerned in the movement. A muscle can contract
at a faster rate, a nerve can conduct impulses more quickly than
ten a second, if they be stimulated artificially. An interesting
contrast is revealed by a comparison of the rates of contraction of
a muscle when it is stimulated respectively through the cortex of
the brain, the corona radiata, the spinal cord, and the motor nerve.
In the last case only is the muscle thrown into such rapid contrac-
tion that complete tetanus is produced.

The rhythm of the muscular response (?*) to volitional impulses

in man is about eight to thirteen per second, the number of waves ©

varying in different individuals and in the same individual under
different conditions of work. A voluntary contraction is an
incomplete tetanus, in which each component is a single con-
traction prolonged long enough to produce imperfect fusion of
the waves.

The conditions which affect the activity of the muscles engaged
in a simple movement can be studied by the apparatus introduced
by Mosso, and called the ergograph. The movements of a finger
or limb are transmitted by a system of levers to a writing point
which marks a graphic record of the movement upon a piece of
smoked paper fixed to a revolving drum. With this instru-
ment many observations (7°) have been made to determine the
influence upon the performance of work of practice, the rate of
contraction, load, rest, hunger, mental activity, various foods and
drugs. Many of the results, however, nwust be accepted with
caution, for there is one source of fallacy which has not been suffi-
ciently recognised by some investigators; \complications can be
readily introduced during an experiment by the influence of sug-
gestion upon the subjects of the research, and it is not possible to
eliminate these entirely by employing as subjects men who have
no special knowledge of, or interest in, the research.

Ergographic studies have shown that general or local fatigue
and hunger diminish, while previous practice, rest, sleep, and food
increase the power of voluntary muscular contraction. These
results are in accordance with the general experience of mankind,

any
int

‘

:

4

THE PHYSIOLOGY OF MUSCULAR WORK — 227

and it is doubtful if a more exact measurement or analysis has
been obtained by such experiments limited to a small group of
muscles.

The ergograph is a convenient instrument for demonstrations,
but the conditions are so different from those of ordinary life that
it is safer to rely upon experience and special experiments, such as
those ! of Zuntz and Atwater, upon men marching or performing
some other kind of general muscular work.

Upon the physical and chemical changes which occur in an
isolated muscle during contraction a vast amount of work has been
done. Here it is only necessary to mention briefly those facts
which have a bearing upon ordinary muscular work. The ex-
tensibility of the muscle is increased during contraction, and its
temperature is raised. Even in the resting condition the muscle
is about 0°1° to 0°6° warmer than the blood which supplies it, and
during contraction an increase of 1:15° has been observed in the
muscles of a dog after the blood vessels had been ligatured. Under
normal conditions, however, the rapid circulation of the blood
distributes the heat so efficiently that the internal temperature of
the body is only raised a degree or two by hard work.®

The blood supply is greatly increased in the active muscle ;
according to Chauveau and Kaufmann’s observations the flow
is 4-5 times as rapid as during rest. The causes of this change
will be considered later in relation to the effect of exercise upon
the heart and circulation. .

The chemical changes are shown by an increased absorption
of oxygen and an increased discharge of carbon dioxide ; a muscle
paralysed by section of its nerve uses 0°003 c.c. of oxygen for one
gramme of its weight per minute, but this is raised to 0°006 or
0-020 c.c. by tonic activity. The glycogen of the muscle de-
creases, owing apparently to its combustion for the supply of
energy. These and other similar questions, including the increased
growth of muscle, must be discussed in a later portion of this
article, which will deal with the general changes in metabolism
during muscular work.

1 See page 233.

* See article by Burdon-Sanderson, “ Textbook of Physiology,” edited by Schafer,
1900, vol. ii., p. 352; and one by v. Frey in Nagel’s Handbuch der Physiologie
des Menschen, 1907, Bd. iv., s. 427. ;

® See page 243.

* Barcroft, Ergebnisse der Physiologie, vii. Jahrgang, 1908, p. 699.

228 THE PHYSIOLOGY OF MUSCULAR WORK

Tue Errects or Muscutar EXERCISE UPON THE HEART
AND CIRCULATION

There is little doubt that the heart is the organ which is most
easily damaged by exercise unsuited to the weak and untrained.
Trainers of both men and animals rightly attach the greatest im-
portance to the condition of the heart, and a vast medical literature
upon cardiac strain, the athlete’s heart, and the soldier’s heart
bears witness to the importance of the subject to the medical man.

It will be well therefore to indicate the most practical methods
for the examination of the heart in relation to the effects of exercise.
There is no question here of a consideration of a heart in a con-
dition of disease, and nothing will be said about inspection, palpa-
tion, percussion, and auscultation, which ate recognised methods
in an ordinary clinical examination. In order to test the capacity’
of a heart to bear the strain of muscular work the most useful
method appears to be a comparison of the rate of cardiac con-
traction at rest, directly after moderate exercise of a few minutes’
duration, and again after periods of five, ten, or more minutes’ rest.
The effect of exercise is an augmentation of the rate; during the
rest which follows the work the beats rapidly decrease in the case
of a strong well-trained heart, but slowly in the case of a weak
and untrained one. The following example of such an observa-
tion (24) will show the contrast :—

| : Trained Man. Untrained Man.
Fi Fi
Rest, | Guereine, | Minutes | Rest, | Usb afteF| acinutes
| 16 33 is | 47 38 | 24
greta 14 30 14 21 40 24
15 26 13 17 38 23

The exercise lasted thirty seconds, and consisted in running
down and up stairs.

In some special cases examination of the heart by means of the
Rontgen rays may elucidate certain questions, but the method is of
limited application and is beset with sources of error. The same
remarks apply to the cardiograph, the records of which may be
so complicated as to be misleading.

The pulse not only furnishes information on the rate and force
of the beat of the heart, but also on the condition of the peripheral
circulation. The sphygmograph affords a graphic record of the

THE PHYSIOLOGY OF MUSCULAR WORK — 229

pulse wave, and in some cases extends the information which may
be obtained by the hand alone. By palpation it is possible for the
practised hand to gauge the pressure of the blood, but for accurate
determinations the Riva Rocci sphygmometer is generally used.

_ The circulation can be studied in several ways; by inspection
the colour of the skin affords a guide to the flow of blood in the
peripheral parts, and the information so obtained may be checked
and extended by the use of flat bulb thermometers with which
the temperature of the surface of the skin can be determined.
The plethysmograph will measure the changes in the volume of
a limb which are due to alterations in the supply of blood, and
modifications of the sphygmometer, which indicate the pressures
at which the arterioles, capillaries, and veins are blanched, will
measure the pressure of the blood in those vessels.

This is not the place for details of the practical use! of the
various instruments which have been mentioned, but it will not
be amiss to point out that the simplest are the best. The striving
for exact results by the use of complicated pieces of apparatus
often defeats the aim; it is far better to multiply simple obser-
vations under different conditions than to spend much time and
labour in obtaining a record with a complicated instrument, how-
ever exact it may appear to be. For this warning there are two
strong reasons. The effects of muscular exercises upon the heart
and circulation quickly disappear when a healthy man takes rest ;
the recovery begins at once, and during the seconds and minutes
spent in the adjustment of apparatus great changes may occur.
The second reason is a practical one. The medical man engaged
in a busy practice has not the time, means, or experience necessary
for the successful use of many scientific instruments, and it is far
better that he should rely upon his own powers of observation by
sight and touch.

In the study of the effects of muscular exercise upon the heart
and circulation it is always necessary to know the normal con-
ditions of the subject during rest. The personal variations in
different individuals are so great that data are deprived of a great
_part of their value unless they combine the results of observations
both before and after exercise.

It is desirable that a writer should give the results of investi-
gations conducted by himself or in conjunction with others. The

1 See “Practical Physiology,” by Beddard, Edkins, Hill, Macleod, and

) Pembrey, second edition, 1905,

230 THE PHYSIOLOGY OF MUSCULAR WORK

following table contains the results of observations! made by
Captain L. E. L. Parker, R.A.M.C., and the author as part of the
work of a committee appointed to report upon the physiological
effects of food, training, and clothing on the soldier.

Individual Variations in the Pulse during Rest.

| Pulse.
Number Average Average
ae et iead of Days. | Time of Day. | ytaxi.| Mint rn ee of Mean
, mum.) mum.) oF each | pr pees of each
Day. Day. Day.
ce afte : 60 10 9-10a.m. (110| 55 | 93 68 80
men \3 6 2 2-3 P.M. 100 | 77! 99 85 92
4 1 10-1 ae. »'|°90:| 72°), 90 72 78
B{ ,° 4 1 2-3 P.M. (100 90) 100 90 93
2 50 | 10 |10.30-11.30 a.m.) 92} 68| 87 72 80 .
12 3 |10.30-11.30 a.m.| 88 | 60| 83 | 68 75
2 {o°} 36 3 10-11 a.m. |104| 60| 99 65 78
©.{ men} 4 20 5 10-llam. |104| 52| 965 59 7
3 3 1 8-8.30 am. | 88) 76 | 38 76 82
15 | 174 | 36 10] 52} 93 | 71 | 81

* Including one of Group B.

The next table gives the results obtained after marching; the
figures are arranged so that the same groups of men may be dis-
tinguished, but are not classified to indicate the influence of dis-
tance, external temperature, clothing, and load.

Individual Variations in the Pulse after Marching.

Pulse.
Number :
Number of _ | Number a {| f
Men. Orationa | of Days. ote Mien anes of| Minton of Mester
7 * | each Day. | each Day. | each Day.
Ad men}® 245 10 | 150 | 70 115 89 | 101
8 1 | 112 88 108 93 101
fe {s 50 10 | 160 72 123 100 112 |
men | 4 12 3 114 72 105 85 95 r
5 15 3 | 126 70 119 78 98
Cf ne {é 20 5 126 80 112 88 101
ments 3 1 138 84. 138 84 117
p{ 6 f6 6 1 | 120 | 93 | 190 93 | 106
359 | 34 | 160 | 70 118 87 104

1 Second Report of Committee, 1908.

THE PHYSIOLOGY OF MUSCULAR WORK — 231

The figures for the pulse in the last table are certainly somewhat
under-estimated, for it was not possible to take all the observations
immediately after the march; the rate of the pulse begins to de-
crease directly the work is at an end, and this is especially the case
in the well-trained man.

These results represent the condition which probably obtains
in active healthy men of the physique of the ordinary infantry
soldier; the men were not picked men, and the data are not to
be considered as rigidly exact, for it was not always possible to
guard against the influence of nervousness in the first examination
and of a brief rest directly after marching.

The next table gives the results of observations in the pulse

of healthy men before and after running :—

Subject. Distance in | Pulse at Rest| Pulse just Pulse atine Rest ne wakes
Miles. before Run. | after Run. Periods. |
C. 1 68 164 98 (15 min.)
. 128 (10 min.), 100 (30 min).
2 70 164 82 (60 min.)
B. {5 76 152 oes
/( $ more = 144 112 (5 min.) |
| 1 56 160 124 (1 min.) |
120 (2 min.), 106 (33 min.) |
2 66 a0 84 (77 min.), 74 (107 min.) |
104 (15 min.), 88 (45 min.) |
2 A 196 86 (75 min.)
.. 70 _ 84 ee
more one * 104 92 (5 min.) |
76 120
more in 140 100 (5 min. ye |

The heart beats more quickly during muscular work. The
object is clear, but the means whereby it is attained are complex.
It has already been shown that a more rapid circulation is necessary
to meet the various demands of muscular activity: the blood sup-
plies these needs, and the heart is the pump which forces it to
circulate through the various parts. The adjustment begins with
the performance of work, and it is necessary to study the means
whereby this is brought about.

The heart and the arterioles are under the control of the nervous
system ; by the action of the vagus nerve the beats become slower ;
they are quickened by impulses passing down the sympathetic
nerve. During rest the vagus nerve appears to exert a constant
inhibitory action upon the heart, but directly impulses pass from

*
- 5 »
® “4 f =
™~ - i .
< ——_ _s -,

232 THE PHYSIOLOGY OF MUSCULAR WORK

the motor cortex of the brain down to the muscles the inhibitory
action is diminished and the accelerator nerve is stimulated.
This is important, for it throws light upon the great influence of
training upon the orderly contraction of the heart, and in relation
' to that subject it will need further consideration later. In addi-
tion to this nervous control, it would appear that other influences
are at work. The products of muscular activity act upon the
heart directly and indirectly through the nervous system; carbon
dioxide is one of the most important of these metabolites, and it
quickens the beat of the heart (**). Muscular work raises the
pressure of carbon dioxide in the alveolar air of the lungs, as
Haldane and Priestley! have shown; the breathing becomes
more rapid or deeper for the maintenance of a constant level in

the pressure of that gas in the alveolar air and presumably in the ~

blood of the lungs. Thus there is a mutual dependence of the
heart and lungs upon one another, and an insight is afforded into
the close association between the heart and lungs which is ex-
pressed by a “ good wind.” Sarcolactic acid is another metabolite
formed during muscular activity, and directly or indirectly may
influence the heart.

The temperature of the body rises during muscular activity,

it may be as high as 102° F. in a healthy man, and it is known |

that the heart responds to an increased temperature by a more
rapid beat. In addition vaso-motor changes occur, more blood
goes to the active muscles and more to the skin when the
temperature rises, and in some cases at least a more rapid beat
of the heart appears to be an effort of compensation for the fall
of blood pressure which may arise from the dilatation of the vessels
in those parts.

The response of the heart to muscular work and to rest is so
extremely rapid that it would appear to be due in the first place
to nervous influences; the effects of metabolites and of the rise in
the temperature of the body develop more slowly and persist for
a considerable time after the work has ceased.

The heart is a muscle, and resembles the skeletal muscles in its
response to work. Gradually increasing work with good nutrition
and periods of rest strengthens it. There is an increased growth,
a physiological hypertrophy which is more or less proportional to

the development of the skeletal muscles. The untrained muscle

1 See page 240.

THE PHYSIOLOGY OF MUSCULAR WORK 233

is overstretched and injured by severe and prolonged exertion,
but the damage is more easily done and less easily repaired in
the case of the heart. The skeletal muscles become fatigued and
painful during movement, and the enforced rest gives them time
to recover; the heart cannot take such a profound rest, it must
continue to beat, if life is to be maintained, and can rest only by
beating less frequently and less vigorously. In the case of the
untrained heart over-exertion produces palpitation, overdistension,
| and dilatation. The duration of systole to diastole, that is, of
| work to rest, may be less than 1:1 in the fatigued heart, whereas
in the normal heart the proportion is 1 : 3.

The increase in the rate of the heart beat is within certain
narrow limits proportional to the work done. The pulse rate
may be readily doubled by running down and up stairs for thirty
seconds, but such vigorous exercise rapidly produces dyspnoea
and cannot be maintained. The heart not only works more
rapidly, but it has to pump the blood into the aorta at a pressure
which may be one-half greater than the pressure at rest. Thus a
healthy well-trained man who had performed such an exercise
showed the following changes in the pulse and blood pressure ;
the pulse was increased from 56 to 124, and the blood pressure in
the brachial artery from 126 to 142 mm. Hg. A high blood pressure
is not maintained, for during the continuation of exercise the
cutaneous arterioles dilate.

The limit of efficiency as regards the rate of the heart beat
appears to be reached at about 160 per minute, but there are
doubtless individual differences.

The influence of marching with a load has been especially
investigated by Zuntz and Schumberg (?*) ; they not only found an
increase in the rate of the contraction of the heart but also evidence
of engorgement of the liver and heart with blood. The frequency
| of increased hepatic and cardiac dulness on percussion was 56, 70,
| and 87 per cent., when the soldiers marched carrying loads of
| 22, 27, and 31 kg. respectively. The average increase of cardiac
dulness was 1 cm., that of the liver 2°3cm.; the highest figures were
35 and 5cm. respectively. The cardiac dilatation involved the right
ventricle on sixty-two occasions, and the left also on thirty-one
occasions. The engorgement did not coincide with the increase in
the rate of the pulse, but with the inereased breathing and the rise
_ in the temperature of the body. In such experiments the belts and

234 THE PHYSIOLOGY OF MUSCULAR WORK

straps of the equipment as well as the load produce a hindrance
to free breathing, but nevertheless the engorgement of the liver
must be considered as a means of relieving the heart from still
greater distension. The tendency to strain upon the heart is
diminished by its increased beat, for the area of the inner surface
of the ventricle exposed to the pressure of the blood is diminished
during its contraction.

After severe exercise the pulse shows an exaggerated dicrotic
notch ; this has been observed in a considerable number of healthy
men, and is no doubt a normal sign of the reaction to the high
blood pressure during work. The following figure is a repro-
duction of a tracing obtained from the radial artery of an athlete
on the day following a severely contested game of Rugby football
in a “ cup-tie ” match.

The blood pressure is the force exerted by the blood upon the —

MII SN

The rate of the pulse was 72 per minute.

walls of the blood vessels, and is dependent upon the pumping
action of the heart and the resistance of the vessels, especially of
the arterioles. The blood pressure will be raised by a more rapid
or more powerful contraction of the heart, if the peripheral re-
sistance remains the same or does not diminish in proportion to
the increase in the work done by the heart. During muscular
work it is known that the peripheral resistance varies; the vessels
supplying the muscles are dilated, and, if the exercise is continued
and the temperature of the body rises, the cutaneous arterioles
expand. This statement applies to those forms of exercise or
work in which there is no prolonged straining effort ; directly the
muscles of a limb are rigidly contracted and the thorax is fixed
in order that a better purchase may be given to the contracting
muscles, as, for example} in lifting a heavy weight, or in wrestling,
a great peripheral resistance may be introduced. During some
efforts the pulse may disappear at the wrist owing to the com-
pression of the arteries by the forcible contraction of the muscles

THE PHYSIOLOGY OF MUSCULAR WORK — 235

and to the hindrances offered to the free passage of the blood
through the heart. For these reasons it is necessary to consider
the nature of the muscular exertion in any discussion of its effects
upon the blood pressure.

M‘Curdy (27) has drawn special attention to this question ;
he recorded the blood pressure in seventy-seven experiments upon
twenty-three men before, during, and two or three minutes after
an exercise of strength or effort. The exercise consisted in the
maximum lift for each man; the weight lifted varied from 118 to
249 kilos., and the time of an average lift was five seconds. The
following are the average values of all the measurements :—

Blood Pressure in Mm. Hg.

Before Lift. | During Lift. | T° aed ha na

111 180 | 110

The highest blood pressure before the lift was 127 mm. Hg.,
the lowest 93; the maximum during the lift was 210 and the
minimum 146. The rise in blood pressure was not accompanied
by any great change in the pulse rate ; some men showed an in-
crease, others no change, and. others a decrease. Such exercises
subject the heart and blood vessels to a great and sudden strain,
and cannot be considered beneficial. A man must be carefully
and progressively trained to lift great weights; otherwise there is
a great danger of overstrain of the heart.

These results may be compared with those obtained by
Bowen (**), who investigated the changes in the beat of the heart
and the blood pressure during bicycling. He found that there
was a rapid rise in the blood pressure when the work began ; the
maximum was reached in about four minutes, but during the con-
tinuation of the exercise the pressure declined slowly. The extent
of this fall depends upon the dilatation of the blood vessels of the
skin, and this in turn depends upon the temperature of the body
and its surroundings. This factor does not come into play during
an effort such as a lift; the powerful and sustained contraction —
of the muscles during the lifting of a weight nearly obliterates the
lumen of the blood vessels, and thereby increases the peripheral

236 THE PHYSIOLOGY OF MUSCULAR WORK

resistance enormously ; the increase in the volume of the blood
driven out of the heart raises the blood pressure quickly to a great
height, because the blood already in the arteries is prevented from
escaping.

The changes in the blood pressure are effected very rapidly,
as is shown by the following examples taken from a series of ob-
servations (7°) upon two men, one well-trained, and the other un-
trained. The exercise lasted only thirty seconds, and consisted in
running down and up stairs.

Trained Man. Untrained Man,
past | Sambar [Pregame nan | getter [Fim ont
110 mm. Hg 134 118 104 134 108
122 =, 134 126 110 140 106
122 -, 152 132 118 126 110
126 142 130 116 148 103
1168. 3, 136 129 122 148 116

The blood pressure does not remain at a high level during the
prolongation of exercise, but falls gradually and may become
lower than it was before the beginning of the work. Such a con-
dition has been observed during a march of seven miles; the fall
in the blood pressure was associated with a dilatation of the
cutaneous blood vessels, which was shown by the increased colour
and temperature of the skin.

The causes of the quickening of the beat beat during muscular
work are to be sought, as already mentioned, in-nervous regulation,
effected reflexly or directly by the products of muscular activity,
and in the action of those metabolites and the rise of temperature
upon the heart itself. It might be expected that the control of
the blood vessels is similarly effected, for the heart is developed
from blood vessels. The evidence from experiments upon the
flow of blood through muscles is conflicting. Gaskell’s (2°) work
led him to the conclusion that vaso-dilator fibres are stimulated
reflexly when muscles contract, but Bayliss (#4) obtained only
slight dilatation on stimulation of the dorsal nerve roots. Lactic
_ acid was found by Gaskell to produce a dilatation of the arteries
of a frog, but Osborne and Vincent could not obtain a similar

result in mammals; carbon dioxide dilates the blood vessels in

THE PHYSIOLOGY OF MUSCULAR WORK ~— 237

the muscles of frogs, as Bayliss has shown. There is no doubt
about the close association of dilatation of the cutaneous vessels
with a rise in the temperature of the body produced by muscular
work. Further observations, however, are necessary to explain
the means whereby muscular work influences the heart and
circulation.

INFLUENCE OF MuscuLAR WORK UPON THE RESPIRATION

Even during rest the differences in the rate and depth of breath-
ing of healthy men are considerable ; some men breathe slowly
and deeply, others take rapid and shallow respirations. The
“tidal air”? may vary from 100 to 1000 c.c., and the total volume
of air breathed per minute shows a similar wide range, the deter-
minations ranging from 3000 to 9000 c.c. These figures have
been taken from the results of different observers ;! in addition
may be given a series (**) recently made upon sixteen subjects, all
of whom, with two exceptions, were medical students :—

|
Volume of Average
Subject. Teen su bag gr pte eee | ger a cnee oe
Months. inches. * Litres, | Pe? Minute. iacekl
1 | 212 154 Blk, 6560 | 225 291
2 | 18-4 132 57 7867 «19°34 406
3 27°1 144 511 7660 | 165. 465 |
4 18 115 5d 9234 =| Ql 441 |
5 21 155 Bll 9°150 17°7 517 |
6 148 91 4°8 6030 | 14 431
7 22°9 173 6:24 9°753 10 981
8 20°4 140 6:0 5113. | 17 300
9 20 133 5°7 5008 =| sid 47 341
10 19°5 129 56 | 6350 | 10 638
11 21 131 56 5'168 | 19 271
12 22°1 123 55 7570 | 194 392
13 20 140-510 9-504 24 396
14 21°6 126 57 5°560 13°5 416 |
15 “| 19% 134 55 ° 7900 17 463 |
16 219 126 56 5458 | 12°4 450
Average} 205 | 134 | 57 7118? | 167 449? |

1 See article Chemistry of Respiration, by M. S. Pembrey, in “ Textbook of
Physiology,” edited by Schiifer, vol. i., 1898, p. 748.
2 Measured at 15° moist.

238 THE PHYSIOLOGY OF MUSCULAR WORK

These results compare very well with those obtained by Haldane
and Priestley (°°) upon fifteen men; the means of their results
were :—

vets | afta | SEER") ree, esi
| | inches. | Mfoiat in Litres, | Pe? Minute. Moist.
—————E———

154 5°11 8°55 | 152 | 604

There is little doubt from the results shown in these two tables
that many of the older estimates, which give much lower figures,
are incorrect.

The composition of the alveolar air is not the same in different
adult subjects, for FitzGerald and Haldane (*4) found that the
percentage of carbon dioxide varied from 5°86 to 4:29 in men
and from 5:40 to 3:99 in women. From this the conclusion
must be drawn that there is a personal variation in the
response of the nervous system to the stimulating action of
carbon dioxide.

The effect of muscular work is always an increased respiratory
exchange and increased ventilation of the lungs to meet the greater
demand for the supply of oxygen and the removal of carbon dioxide.
The breathing becomes quicker or deeper, or more often is affected
in both ways; hyperpncea is produced and, if the work be severe,
laboured breathing or dyspnoea may follow and give rise to so much
discomfort that the man will pant and stop work to “recover his
breath.”

At rest the healthy man breathes through his nose; the in-
spired air is warmed, moistened, and cleansed of foreign particles
by passing over the moist surface of the nose and naso-pharynx.
During vigorous exercise, however, mouth-breathing constantly
replaces nasal breathing, for there is then less resistance to the entry
and exit of the air, and the exposure of the moist vascular surface
of the mouth assists in the cooling of the body. The man who
resists the inclination to breathe through the mouth during active
exercise throws an additional and unnecessary amount of work
_ upon his respiratory muscles, and thereby increases his discomfort
and distress.

The increase in the ventilation of the lungs during exercise

THE PHYSIOLOGY OF MUSCULAR WORK ~— 239

| may be shown by the following examples from experiments upon
three healthy men :—

Ventilation No. of
Subject. | in Litres | per Respirntions. Ratag «eee Remarks.

B. 1 18 60 _—_ At rest.
15 31 124 —- After running ¢ of mile.

| 9 29 70 At rest.
| 12 22 84 | After running } of mile.

C. 1 20 72 At rest.
143 25 110 After running } of mile.

The causes of hyperpnoea and dyspnoea have been the subject
of many experiments and much controversy, and even at the
present time it is impossible to maintain that the question is closed.
It is generally admitted that the work of Haldane and Priestley (*)
has shown that the factor which regulates the respiratory move-
ments during rest is the pressure of the carbon dioxide in the
blood, as gauged by the pressure of that gas in the pulmonary
alveoli. The rate of breathing may be altered, but the subject
of the experiment will also change the depth, so that the mean
pressure of the carbon dioxide remains almost the same, as shown
by the following results obtained by these authors :—

Percentage of Carbon Dioxide
in Alveolar Air.
sues. | Sara
At End of _ At End of Mean
Inspiration | Expiration. ;
9 5°59 5°87 5°73
: J. 8. H. ; 19 5°56 | 5-70 5°63
)
9 533 | Csi '47 5°40
J. 8. H. { 20 5°44 | 5°60 5°52
: 105 595 | 674 6°35
J.G. P. { 30 598 =| «= 6:05 6-02

During muscular work Haldane and Priestley found that there
was a slight but distinct rise in the percentage of carbon dioxide
in the alveolar air. Their results are given in the next table.

-
-
*

240 THE PHYSIOLOGY OF MUSCULAR WORK

Effects of Work on the Percentage of Carbon Dioxide in the

Alveolar Air
weir Gaeaiaiea | Alveolar CO, per Cent. |
Subject. Foot-Pounds ane mae | mae | =
r ie
se niacaa Normal=1. Fastration: cptretion.
_— : i ee eS
i ee: 1880 rs 5'10 5:80 =| «545
4140 ie 5°56 6°51 | 6-085
4850 a 5:20 619 | 5695
3380 ea 5-42 578 | 560
3160 i) 5:79 5:88 | 5835
2530 ae 5:48 6°15 5815
Mean J. S. H. 3320 49 544 6°05 5°75
Mean J. S. H. Rest 1 5°54 | 5:70 5°62
Spare eae 2420 - 653 | 713 | 683
1940 = 661 | 651 6°56
2460 at 660 | 7-04 6°82
2540 - 6:06 | 7:26 6.64
Mean J. G. P. 2340 38 645 | 6-98 6-72
Mean J. G. P. Rest 1 617 | 639 | 6-28
Mean of J.S.H.| 2800 43 5945 D1 | «6-235
and J. G. P. Rest 1 | 5855 | 6045 | 5:95

From these data they conclude that the hyperpnoea of muscular
work is due to a_rise in the pressure of carbon dioxide in the res-
piratory centre, but it is necessary to bear in mind that they
measured the pressure of carbon dioxide in the alveolar air, not
in the blood.

The history of the different views upon the causation of the
hyperpnceea produced by muscular work illustrates extremely well
those fluctuations between old and new theories which are so
constantly observed in the biological sciences. Muscular activity
increases the ventilation of the lungs, the intake of oxygen and the
output of carbon dioxide. It was but natural, therefore, that the
hyperpneea should be attributed to a deficiency of oxygen or to
an excess of carbon dioxide in the blood due to the greatly in-
creased metabolism. To these causes hyperpnoea was generally
attributed until Geppert and Zuntz (**) found that muscular activity
was accompanied by an increase in the oxygen and a decrease in
the carbon dioxide of the blood. These observers considered that

THE PHYSIOLOGY OF MUSCULAR WORK 241

the hyperpnoea was produced by some product of muscular activity
which was absorbed by the blood, and thus carried to the medulla
oblongata, where it stimulated the respiratory centre. Loewy (%7)
also maintained that carbon dioxide was not the factor, for he
found that, whereas the rate of respiration was doubled by muscular
work when the increase above the normal amount of carbon dioxide
in the expired air was only 0°5 per cent., the same amount of
_ dyspnoea could be produced during rest only by artificially raising
the percentage of carbon dioxide to a much higher point, about
5 per cent.

The alkalinity of the blood is diminished during muscular
activity, and this observation revived the question whether pro-
ducts of activity stimulated the respiratory centre. Forty years
ago Pfliiger (°°) suggested that lack of oxygen might act indirectly
as a stimulus to respiration; products such as lactic acid un-
oxidised owing to the deficiency of oxygen in the tissues might

be the exciting agents.

The work of Haldane and Priestley effected a return to the
view that carbon dioxide was the chief factor which increased the
respiration during muscular work. But quite recently the whole
question of muscular hyperpnoea and dyspnoea has been reopened,
and it is necessary to consider the possible action of such factors
as lack of oxygen, metabolites such as lactic acid, increased tem-
perature of the body and nervous impulses from various parts.
The muscular work performed by Haldane and Priestley was
slight, and their analyses of the alveolar air do not include the
amount of oxygen. After vigorous exercise the alveolar air some-
times shows a considerable rise in the percentage of carbon dioxide,
and at other times a fall below the normal (*°). It becomes im-
portant, therefore, to determine the respiratory quotient, the ratio
of the carbon dioxide discharged to the oxygen absorbed. Such
analyses show quotients as high as 1:2 during muscular dyspnea.

It is necessary to consider whether the lack of oxygen produces
dyspnoea directly or indirectly through metabolites which remain
unoxidised owing to the lack of that gas. A man at rest breathes
with practically the same frequency and depth whether he be
breathing air or pure oxygen (*), and his response to an increase of
carbon dioxide in his lungs appears to be unaffected by breathing
oxygen (*'). Directly after exercise, however, breathing oxygen
_ diminishes the dyspnoea, and enables the man to tolerate a higher

; Q

242

THE PHYSIOLOGY OF MUSCULAR WORK

percentage of carbon dioxide. The following are examples of
the results obtained :—

Composition of Mixture in Spirometer at Breaking Point.

Subject. | Started with Started with Pare
Per Cent. Per Cent.
Ear ee sb 3500,
A. B
After exercise { we vs ao 0.

|
|
|
|

The complexity of muscular dyspncea is shown by the fact
that it does not increase if the exercise be continued, but on the
contrary decreases. This is well known to athletes. During the
first quarter of a mile run the hyperpncea increases until panting”
and distress are experienced, but if in spite of the discomfort the
run be continued the difficulty of breathing disappears and the
exercise can be maintained with comfort at the same or even at a
greater pace.
interesting phenomenon has not been thoroughly investigated,
but it would appear that the distress is associated with a high
respiratory quotient, with a relative deficiency of oxygen (4).

Composition of Alveolar Air before and after the Advent of

The runner has now

6c“

got his second wind.”

“ Second Wind.”

This

| Percentage Percentage co Pulse Rate
Subject. | of Carbon of Rated E in 15 Remarks,
Dioxide. | Oxygen. 0, Seconds.
Pp: 5-11 ae ee 19 Rest.

5:55 15-49 10 30 After 8 laps (} mile);
panting ; pulse irre-
gular.

5°50 15°39 0°99 35 After 18 further laps;
“second wind” at
10th lap; pulse more
regular ; sweating, f

R. 5:27 14°32 0:79 ye das is
7:36 14:03 1:06 After 6 laps.
591 14-62 0°93 After 8 further laps;
“second wind” ; sweat- .
ing,
B. 6:04 1448 | 093 19 Rest.

8:13 13:17 1-04 38 After 8 laps,

7°39 12°8 0:90 36 After 19 further laps ;
“second wind” at
16th lap; sweating.

THE PHYSIOLOGY OF MUSCULAR WORK 243

Other factors are probably involved in these conditions; the
contraction of the heart is often irregular during the period of
distress, and becomes regular when the “ second wind ” has arrived.
A rise in the temperature of the body, vascular changes and sweat-
ing, also accompany “second wind,” and further experiments
are necessary to determine their significance in relation to the
respiratory movements.

Ryffel has found lactic acid in the sweat and urine after muscular
exercise, but no pronouncement can be justly made for or against
the theory that lactic acid stimulates the respiratory centre.

It is known that a rise in the internal temperature (**) of the
body quickens the respiratory movements; this is especially

- marked in the dog; the rate of its respiration may be increased
from 28 to 230 per minute when it is necessary for it to cool its
body by the evaporation of moisture from its tongue and mouth (*).

It is probable, moreover, that nervous impulses from various
parts of the body, especially from the heart and lungs, may in-
fluence the activity of the respiratory centre and produce such
a co-ordination of the respiratory movements that an adequate
supply of blood is maintained through the lungs. The sensory
nerves of muscles may take part, for the respiratory movements
are altered in type, rate, and depth by the nature of the exer-
cise performed. During rowing a well-trained man adjusts his
breathing to his stroke. ;

The quantitative changes in the respiratory exchange during
exercise will be considered later in connection with the exchange of
material, of which they form an essential part.

—— lO aS

INFLUENCE oF MuscuLarR EXERCISE UPON THE TEMPERATURE
OF THE Bopy -

It is necessary here, equally with the other systems of the
body, to consider the normal variations in the temperature of the
body. One might maintain that it is more necessary, for on ther-
mometers and temperature charts the point 98°4° (36-89°) has
been marked as the normal ; this practice has had the unfortunate
result of preventing the full recognition of the daily and personal
variations in the temperature of man. Confusion is still greater
when it is remembered that many physicians rely upon the tem-
perature of the mouth, others upon that of the axilla, and a

—?

244 THE PHYSIOLOGY OF MUSCULAR WORK

small number upon that of the rectum. It is easy to appreciate

the reasons of delicacy which prevent the determination of the

temperature in the rectum in the case of most patients, but there
is no excuse for the constant neglect on the part of clinicians to

mention in their reports the time and place where the temperature

was taken. Accurate results can only be obtained by the deter-
mination of the temperature in the rectum or stream of urine,
for the cavity of the mouth is bounded by such thin walls, and
is so readily cooled by exposure, breathing, and sweating, that
it often does not indicate the true internal temperature of
the body.

The temperature of man shows a daily variation; it rises
during the day, the time of activity, and falls during the night,

the time of rest and sleep. The range is from 36-0° (96°8°) to

37°8° (100°0°); these are average figures for the temperature of
the rectum and urine, and do not include the absolute physio-
logical range.

The temperature is raised during muscular work (*); it may
be as high as 38°9° (102°) in a healthy man. This truth is now
generally accepted, although a few years ago, owing to observa-
tions based upon temperatures taken in the mouth, it was generally
denied or contested. The explanation of the disagreement is found
in the fact that the temperature of the mouth may fall during the
time that the temperature in the rectum and urine is raised.

The heat of the body depends upon the production and loss of
heat. During muscular work the production is greatly increased,
owing to the vigorous combustion of material in the tissues, espe-
cially in the active muscles. This combustion is indicated by
the great rise in the discharge of carbon dioxide and in the ab-
sorption of oxygen. The loss of heat also undergoes an augmenta-
tion, otherwise the temperature of the body would steadily rise,
and would soon reach a height incompatible with the performance
of work and even with life itself. Indeed this does occur under
special conditions, when a man is forced to work in a hot atmos-
phere so laden with moisture that the cooling of his body by the
evaporation of sweat is prevented.

Under ordinary conditions the effect of muscular work is to
cause a rise in the internal temperature ; the increased production
of heat is not compensated by a corresponding loss. It appears

that a rise of temperature, within certain narrow limits, is bene-

THE PHYSIOLOGY OF MUSCULAR WORK 245

ficial. The chemical changes associated with muscular work are
probably facilitated by a temperature a degree or two above the
temperature during complete rest, and it may be that the dilatation
of the blood vessels of the skin relieves the heart from too great a
blood pressure. Most men find that they can work more com-

fortably and efficiently when they have “warmed up” to the
work, and some maintain that they work better when they begin

to sweat. The first half mile of a walk is not so well performed as
the later portions. Such evidence, however, would not justify a
statement that the improvement is solely due to a rise of tem-
perature, for there are other factors to consider. Among these

_ should be mentioned the adjustment of the heart and respiration,

the increased flow of blood through the muscles, and probably an
increased secretion of synovial fluid in the joints. This much,
however, may be said. Muscular work both in the case of man
and other warm-blooded animals is constantly accompanied by a
rise in the internal temperature; the time of activity coincides
with the rise in the daily variation of temperature, the time of
rest and sleep with the fall to the minimum. Moreover, the daily
variation in temperature is accompanied by corresponding changes
in the pulse and the respiratory exchange.

The following table will show the effect of various forms of
exercise upon the temperature of man :—

Temperature before Temperature after
Exercise. ercise,

Subject. Remarks.

Urine. ‘Rectum, Mouth.| Urine. |Rectum.

Mouth.
Degrees. ees.| Degrees. Degrees. | Degrees.
00| 3722| 37-67| 3645 3794| 38°00 Walk of about 4 miles,
‘80| 37-22| 37-55) 36-32) 37-83| 37°94) Digging for 45 minutes.
Sa ... | 36°60 | 38°35| 38°70 Work for about 2 hours
in snow.
P. | 376 | 372 | 376 | 37:°3.| 38:0 | 38:1 | Bicycle ride for 3}
. miles; temperature
of air in shade, 33°6

d
36°22) ... ... | 38°40 Pian iger of Simelihorn
(2752 m.).
37°53 | 36°67 | 37-72) 38-13 or seat ride for about
20 miles.
-36°78| .... | 39:00) Game of fives for 30
36°22; ...° | 38°89 minutes,

246 THE PHYSIOLOGY OF MUSCULAR WORK |

In addition to the above data may be given the results of
observations upon soldiers after marching : |—

Number) Number | Number} yj. Mini- Average of | Averageof | Average of
ts) of — mat | ants Maxima of Minima of Mean of
Men. |Observations.| Days. | ™U™- ) mm | each Day. each Day. each Day.
21 359 | 34 |102-4° | 98°8° 101°4° 100:2° 100°7°
(39°11) (37°11) (38°56) (37°89) (38°17)

In observations upon the temperature of the body it is necessary
to determine both the deep and surface temperature, for there is
no doubt that the greatest discomfort arises when the temperature
of the skin is abnormal. It is in the skin that the sensations of
heat and cold arise. A rise in both the deep and surface tem-
perature shows that the body is warmed in all its parts, and dis-
comfort is then experienced: if, on the other hand, the skin be
kept cool by sweating or exposure, no discomfort and no bad
effects are experienced by a healthy man whose internal tempera-
ture has been raised a degree or two degrees by hard work. After
exercise the temperature of the body falls, and the reaction is
generally seen in a temperature below the normal for a day
of rest.

All men know that it is easier to work hard if the clothing be
sufficiently light and loose to allow of the free evaporation of
sweat. Work can only be performed efficiently under such con-
ditions on a warm and damp day. When a labourer keeps on
his coat he does not mean to do a fair day’s work, and there
is very little doubt that he is being paid by the day and not
by the piece.

A man who is not forced to work finds in his sensations of
heat a safeguard against overwork and heat-stroke; he works
more slowly when he feels too hot, or, if he «wishes to continue to
work hard, he increases his loss of heat by the removal of his
coat or waistcoat and by turning up his sleeves. The evapora-
tion of sweat is thus facilitated, as shown by the following
comparative observations? upon soldiers after a march of seven
miles :— ~ 2

1 Committee on Physiological Effects of Food, Training, and Clothing on the
Soldier, Second Report, 1908. (
* Ibid., Fourth Report, 1908,

THE PHYSIOLOGY OF MUSCULAR WORK = 247

In in Rectal | Loss of Moisture from Increase in External
Increase in Pulse.| “Temperature. | Body inGrammes. | W¢lghtofClothes| Tempera.
Max.) Min. |Aver.| Max. | Min. Aver.| Max. Min. | Aver. | Max. Min. |Aver. Ra —
——S ——— | —S EE
52 | 16 | 28 |1°6° F.|0°6° 1:07] 1430 | 1000 | 1200 | 250! 0O|109|67°| 58°
48 | 24] 41 /1°8 0°8 (15 2000 | 1200 | 1500 480) 90 | 254! 69 59
|

and load.

* Drill order without jacket.

+ Drill order with jacket.

When the temperature of the air is high both by the dry and
wet bulbs the evaporation of sweat must be greatly increased in
order to cool the body. This is shown by a comparison of the
results obtained upon the same men, when they performed the
march on hot and cold days with the same clothing, equipment,

Increase in Pulse.

Number of Men.

sei Min.

me

84 | 52

24; 8

-
7

.| Max.

16

2°3° F.

Increase in Rectal
Temperature.

Min. | Aver.

1°4°
0'8

|

Loss of Molatare £ | Increase in External
Body feagerntcaials Pee eee isp rr
Max. | Min. | Aver. | Max.) Min. |Aver. nt c-
: ea SS ee
2390 | 1140 | 1816 | 640} 60 | 320! 79°| 67°5°
555 3CO 419 | 40} OO] 27) 45 | 38

—_

The limits of the regulation of temperature are passed when

a man is obliged to work under unfavourable conditions of clothing
in a very hot and moist atmosphere ; the temperature of his body
rises to an abnormal height; the production of heat exceeds the
loss, and a point is soon reached at which the metabolism becomes
extravagant; more and more heat is produced, and heat-stroke (**)
is the result. This condition is seen in soldiers forced to march
carrying a load, and wearing unsuitable uniform and equipment
in a hot and humid atmosphere.

1 Committee on Physiological Effects of Food, Training, and ater: on the
Soldier, cond Report, 1908,

248 THE PHYSIOLOGY OF MUSCULAR WORK

THE INFLUENCE OF MuscuLAR Work UPON THE EXCHANGE
OF MATERIAL

It has already been pointed out that the law of the conser-
vation of energy applies to the performance of muscular work,!
and data have been given to prove the great increase in the intake
of oxygen, the output of carbon dioxide and the production of
heat. The respiratory exchange represents only a portion of the
total exchange which must be determined in any experiment upon
the total income and output. The nitrogenous exchange must be
estimated from the total nitrogen of the food ingested and of the
urine and feeces excreted. In addition, the composition of the
food in terms of carbohydrate and fat as well as of protein should

be known, and also the amount of water taken in by, and discharged —

from, the body.

It is impossible in this article to consider this subject fully,
but attention may be directed to the chief results of experiments.
The nitrogenous output is dependent upon the intake of nitro-
genous food, not upon the performance of muscular work; the
intake of oxygen and the output of carbon dioxide are immediately
raised by muscular exercise, and under normal conditions are pro-
portional to the work done. It will be understood that the term
work is here used in the sense of physiological work which may
or may not be immediately apparent as physical work expressed
in foot-tons or kilogrammetres. The first time a man performs
work, to which he is unaccustomed, he expends more energy than
he will do in performing the same work after. frequent practice.
One of the most important effects of training is the economical
performance of work.

The fact that the nitrogenous output is not increased by work
would suggest that the energy is supplied by carbohydrates and
fats. It is necessary to give briefly the evidence upon these points.
In the first place the experiments of Pettenkofer and Voit (*") show
that: the excretion of nitrogen in the urine is the same whether a
man does work or is at rest; the output of nitrogen is determined
by the amount of that substance taken in the food. In their first
series of experiments the mean excretion of nitrogen in the urine
during hunger was 12°4 grms. during a day of rest and 11°8 grms.

1 See Atwater, Hrgbenisse der Physiol., 3ter Jahrgang, Abtheilung 1, 1904, s. 497.

,

- —_—

THE PHYSIOLOGY OF MUSCULAR WORK 249
during a day of work, the time of labour being nine hours. In

the series of experiments when the man received food the figures

were 16°8 grms. during rest and 17:1 grms. during work. There
is no increase in the discharge of nitrogen on the days following
the work, provided that the man started with stores of energy
in the form of glycogen and fat sufficient to prevent any demand
upon the protein of his tissues to supply the energy required for
the performance of the work.

There is no doubt that the amount of food required by a man
depends upon the muscular work which he performs. So much
follows from our knowledge of the conservation of energy, but

_ that law gives us no guidance as to the relative amounts of protein,

carbohydrate, and fat which are required. To obtain evidence upon
these points we must examine the diets of men whose occupations
entail different amounts of manual labour.

Atwater calculated the energy value of the dietaries of civilians
living under different conditions, and upon these data based his
well-known standards of diet. These are given in the table on
the following page, together with other dietaries for the sake of
comparison.

Special importance must be attached to the dietaries of prisoners
both military and civil, for in these cases it was impossible for
the men to obtain extra food ; work was regularly performed, and
medical inspection and the weights of the men at different times
showed that their health was satisfactory.

During the last two or three years special attention has been
directed to the question of diet. Chittenden’s (*%) experiments
and writings have given rise to much discussion, for he maintains
that most men eat too much protein and impair their health by
this extravagance. His contention is that the large amount of

_ protein consumed overtaxes the kidneys in their work of excreting

the waste products of digestion. For this he gives no evidence.
On the other hand it is well known that the body is overcompen-
sated and is able to adjust itself within certain limits to a wide
range of work. This capacity is no doubt shared by the kidneys,
for one kidney may for years efficiently remove the waste products
which are normally discharged by two kidneys.

It is impossible here to examine fully Chittenden’s experiments
and views, but it may be well to emphasise again the importance

__ of instinct and experience as guides to questions of food. Healthy

THE PHYSIOLOGY OF MUSCULAR WORK

250
| Protein. | Fat. ayorates Calories. Remarks,
| |
Grammes. Grammes. Grammes.
No work 4 | Pe 2700 ae jac of
. : s at and carbohydrate
Light work E 110 3000 aoe. give bus
Moderate work . .% 125 3500 they must be suffi-
Hard work 3 150 | 4500 cient to make upwith
; 8 | the protein the num- | ,
Very hard work | oe | 5500 ber of calories, The
i standards are for
| food actually eaten.
Average food sup-| 133 | 115 424 3369 | Waste included, but
pe gratis to four not extra food
ritish regiments ! bought.
British soldiersinde-| 127 — 65 497 3272 | Rations allowed.
tention undergoing |
sentences exceeding
forty-two days with-
out hard labour !
British soldiers in de- | 141 69 560 3614 | Rations allowed.
tention undergoing
sentences exceeding
forty-two days with
hard labour +
Ordinary _ prisoners,| 135 35 536 3115 | Food supplied.
Scotland,light work,
mostly sedentary
Convicts, Scotland,| 173 57 602 3707 | Food supplied.
“hard labour,” so
called ;
Food supplied free, 91 48 406 =) Seamen and boys are
seamen, Koyal Navy! '| also allowed 4d. a
Food supplied free,| 107 69 406 2845 | day to buy the extra
boys, Royal Navy1 food required.
British army mini-} 138 105 528 3903
mum war ration
(South Africa) *
Russian army war| 187 27 775 4891
ration (Manchuria)!
Japanese army war| 158 27 840 4343
ration (Manchuria)!
Members of two col-| 225 334 633 6812 | Food eaten.
lege football teams, ;
United States of
America

1 Third Report, 1908, Committee on Physiological Effects of Food, Training,

and Clothing on the

Soldier.

fe

ly

THE PHYSIOLOGY OF MUSCULAR WORK 251:

men and animals do not eat too much, if they perform an adequate
amount of work.

The increased consumption of food which is associated with
muscular work generally involves an increase of protein, carbo-
hydrate, and fat, as shown in the dietaries already given. There
is need of more protein, even although it is agreed that the destruc-
tion of that substance in the body ‘is not increased by muscular
work: there is a retention of nitrogen during muscular work, and
this nitrogen appears to be stored or built up in the body as protein.
Bornstein ! found that he retained in eighteen days an amount of
nitrogen which would correspond to 800 grms. of muscle. Muscles
develop during work, and thus the protein of the tissues is increased.

For the supply of energy during muscular work the carbohydrates
and fats are increased. These foods stuffs can replace one another,
for fat is formed from carbohydrate in the body, and there is evi-
dence to show that fat may give rise to carbohydrate. The relative
amounts of these articles of food selected by different men appear
to depend upon individual tastes and the comparative cost. Fat
is dearer than carbohydrate, but it is a concentrated food.

The energy values of the different foods are most conveniently
expressed in terms of the heat which they yield on combustion.
One gramme of dry protein or of carbohydrate yields 4:1 calories,
and an equal weight of fat yields 9:3 calories. The protein does
not undergo complete combustion in the body; for this reason
the physiological value given above is less than the physical value
as determined by the calorimeter. For the supply of the energy
needed during the performance of muscular work the different
food substances can be substituted according to their equivalent
quantities ; thus 100 grammes of fat, 211 grammes of protein, and
230 grammes of carbohydrate are physiologically isodynamic. The
- muscles obtain energy from each kind of food, but the carbohydrates
and fats are the ones most readily used. The relative quantities
will depend upon the diet ; carbohydrates form a large proportion
of the food consumed by most working men.

A man absorbs per kilogramme of his body weight and per
hour about 0°29 grm. of oxygen and discharges about 0°33 grm.
of carbon dioxide, when he is at rest; directly he performs work
the respiratory exchange increases, thus a walk at the rate of about
three miles an hour will raise the values four or five times. If

a See Cohnheim, Ergebnisse der Physiol, Zweiter Jahrgang, Abtheilung 1, s. 621,

SS = ~~ 7 “ —

a

the work be of an unusual kind the exchange is much greater the
first time that it is performed, but by practice it may be reduced
to two-thirds of its original value. This economical working of the
muscles is one of the most striking results of training. The well-
trained body is far more efficient than the best engine.

252 THE PHYSIOLOGY OF MUSCULAR WORK

INFLUENCE OF MuscuLaR WoRK UPON THE GLANDULAR
; SysTEMS

It is impossible to consider this subject fully within the limits
fixed for this article, but attention may be directed to two im-
portant glands, the kidney and the sweat glands.

The sweat glands are thrown into activity by muscular work,
and the evaporation of the sweat cools the body and removes waste —
products. Figures + have been given to show how large an amount
of water and heat may be removed from the body in this way.
During work the production of heat is raised four or five times,
but the increased loss of heat due to the exposure of the blood
in the dilated vessels of the skin is insufficient to prevent the
temperature of the body from rising to a dangerous height. The
cooling of the body in such a case is effected by the evaporation
of sweat and moisture from the respiratory tract. A very striking
instance of the limitations and dangers incurred by a failure to
sweat has been recorded by Zuntz and Tendlau (*). The man
upon whom they made observations had no sweat glands, and
directly his temperature rose to 39° on exposure to the sun or as
the result of moderate work he breathed double as much air as
during rest. His skin was flushed with blood, but these efforts of
compensation were insufficient to prevent his temperature rising.
He found that he could continue to work in summer only by
frequently soaking his shirt in water; with this wet covering on
his body he was able to supply a substitute for sweat.

The great loss of moisture during sweating reduces the amount
of water secreted by the kidneys, unless an adequate supply of
water be taken by the mouth. The urine is concentrated, and on
cooling throws down a Jeposit of urates. After vigorous exercise
albumin is frequently found in the urine. This so-called “ func-
tional albuminuria ” MES investigation on account of its

1 Pp 247.
\ age

\ e
\ .
\

THE PHYSIOLOGY OF MUSCULAR WORK ~ 253

great medical importance. The majority of the best athletes
examined have passed albumin in their urine after contests in sport,
such as rowing, running, and football (°°). Is this albuminuria to
be considered pathological or physiological? It is probably the
expression not of disease but of disturbance in the supply of blood
and oxygen to the kidneys during strenuous work. This is pro-
bably the reason why most cases of albuminuria are found among
the best cfews and teams; the men with the best physique and
the best training are capable of the greatest exertion. During
rest the albuminuria disappears.
The subject demands attention, for there is no doubt that men
have been rejected for life insurance on account of this albuminuria,
and many have been treated as the subjects of serious disease of the
kidneys. It is difficult to imagine how much worry and misery
may have been caused by the failure to recognise that albuminuria
is not necessarily a sign of renal disease.

MuscutarR Work As A CAUSE oF FATIGUE

Fatigue is a condition which it is very difficult te define or
analyse. Excessive activity of any part of the body brings about
a state of increasing inefficiency. The chief characteristic of
fatigue is inefficiency, and a classification of fatigue might be based
upon its apparent seat of origin. Fatigue due to muscular activity
alone needs consideration in this article, but it must not be thought
that the condition is one in which the muscles alone are involved ;
it is impossible to exclude other parts of the body, for muscular
activity affects all parts ; the body works as a whole.

Muscular work produces fatigue, and its onset depends upon
the nature of the work, its duration, and the external conditions
-under which it is performed. An analysis of the sensations of
this fatigue shows that there is a local fatigue, a muscular soreness
and discomfort due to the excessive use of one group of muscles,
and a general sense of fatigue which follows a more uniform activity
of the muscular system, Local fatigue may quickly manifest itself
when a special movement, to which the body is not accustomed,
is performed. The muscles quickly tire and respond with weaker
and less orderly contractions. The causes of this condition are
not well known, but it would appear that lack of sufficient nutri-
_ tion, including oxygen, is one of the most important ; waste pro-

254 THE PHYSIOLOGY OF MUSCULAR WORK

ducts such as lactic acid may be formed and may injuriously affect
the activity of the muscle fibres or their nerve endings. It may
be, as Hough (*') and Hill (5*) have suggested, that the muscular
soreness experienced during work and for some hours afterwards
is due to the waste products of activity, such as lactic acid.

There is another kind of muscular soreness which is not ex-
perienced at all during the time of exercise, but is felt the next
day as an uncomfortable or even painful stiffness which gradually
disappears during movement, but may be noticeable for two or
three days. This form of soreness Hough thinks may be due to
ruptures within the muscle fibres. It is difficult to obtain evidence
upon this point, and it would appear more reasonable to attribute
it to similar causes to those given for the first kind of muscular
soreness.

The onset of fatigue, both local and general, can be delayed —
or largely prevented by progressive training. This may be due
to the fact that the body by practice performs work more econo-
mically and adjusts more readily the circulation of the blood to
meet the general and local needs of nutrition. It may be that
the body acquires an immunity to its waste products or increases
its capacity for oxidising or otherwise rendering them inert. The
‘receptive substance”? between the nerve and the muscle may
be an important element in muscular fatigue.

Weichardt (5%) maintains that there is a toxin which causes
fatigue, that this toxic substance is not lactic acid, and that the
living body produces an antagonistic substance, an antitoxin.
The injection of blood, serum, or other fluids containing the toxin
is said to produce in an animal all the signs of fatigue, unless it
has been previously protected by a dose of the antitoxin. These
observations need confirmation, but in support of the view other
arguments have been advanced. The toxicity of the urine is
increased by muscular exercise and the sweat secreted during
hard work is toxic, whereas that poured out by a man at rest but
exposed to a heated and moist atmosphere is free from harmful
substances. It is well known that an untrained man experiences
the day after hard and prolonged exercise a general feeling of
lassitude and disorder; this has been attributed to an auto-intoxi-
cation or poisoning by the products of the unusual muscular activity.

Ryffel has found that even after moderate exercise lactic acid
can be detected in the urine and sweat, but further observations

THE PHYSIOLOGY OF MUSCULAR WORK ~— 255

are necessary to show the relationship of this substance to
muscular fatigue.

Undue stress is frequently laid upon the capacity of the heart
to perform work. This is not peculiar to the heart, a similar
condition is seen in the respiratory muscles. Their activity is
rhythmic, work followed by rest; they have been progressively
trained from birth and work efficiently and economically. By
constant practice a corresponding capacity for work can be
developed in the ordinary muscles of the body. When an
unusual amount of work is thrown upon the heart and the
respiratory muscles, signs of fatigue are observed in them similar
to those shown by other muscles.

The absence of fatigue in nerves need not be discussed here,
for in the living body the nerve is a part of the nerve cell, and the
nerve cells are without doubt subject to fatigue. How largely
the nervous system is involved in fatigue is shown by the fact
that a much greater amount of work can be performed, without
the immediate experience of fatigue, when the subject is spurred
on by nervous excitement. The fatigue, however, in these cases
is only postponed, and the reaction is greater. The nervous ex-
citement inhibits the sensations of fatigue, and under such con-
ditions the body can be readily overtaxed.

Nervous impressions may diminish the sensations of fatigue ;
soldiers at the end of a long-march step out more briskly when
the band strikes up a lively tune. The interaction between the
nervous and muscular systems is of the closest nature. Good
mental work cannot be done after a hard day’s sport, and study
for a serious examination is incompatible with training for a race.

Fatigue is a protective sensation, a warning that the body needs
rest. .There is nothing to be gained by resisting it by the use of
_ drugs. Work performed under such conditions is extravagant, and
the price is paid later in a greater reaction and depression. The
decrease in the general sensibility produced by fatigue renders a
man unmindful of discomforts which under ordinary conditions
would be intolerable; he can sleep profoundly and thus restore
his energy.

The rational method is to prevent as far as possible the con-
ditions which are favourable to fatigue. Progressive training
enables the body to work more economically, to adjust the supply
_ of blood to the needs of the various parts, and to strengthen the

256 THE PHYSIOLOGY OF MUSCULAR WORK

body uniformly, so that no extra strain is thrown upon it by the
early failure of any part, especially of the heart and lungs. This
method has stood the test of experience, and is the only one recog-
nised by good trainers of athletes and horses.

BIBLIOGRAPHY

+ Ranvier, Arch. de physiol. norm, et path., 1874.

* Haycraft, Journal of Physiology, vol. xxxi., 1904, p. 392.

% Halliburton, Journal of Physiology, vol. viii., 1887, p. 133. Biochem-
istry of Muscle and Nerve, 1904.

“ Von Fiirth, Ergebnisse der Physiol., 1902, i., Abt. 1, s. 110.

5 Mellanby, Proc. Physiol. Soc., Journ. Physiol., 1908, vol. xxxvii., p. xxxiv.

® Brodie and Richardson, Phil. Trans. Roy. Soc., 1899, B, vol. exci., p. 127.
Vernon, Journ. of Physiol., 1899, vol. xxiv., p. 239.

* Leathes, Problems in Animal Metabolism, 1906, p. 99 ; Journ. Physiol.,
1904, vol. xxxi., p. ii.

8 Fletcher and Hopkins, Journ. Physiol., 1907, vol. xxxv., p. 247.

® Mellunby, Journ. Physiol., 1908, vol. xxxvi., p. 445.

10 Bunge, Zeitschr. f. physiol. Chem., 1885, Bd. ix., s. 60.

4 Macallum, Journ. Physiol., 1905, vol. xxxii., p. 95.

12, MacMunn, Proc. Physiol. Soc., Journ. Physiol., vol. v., 1884, p. xxiv.
Phil. Trans., 1886, p. 267. Pete f. physiol. Chem., 1888, "Bd. 13, s. s. 497,

13 Mérner, Jahresber. f, Thierchem., 1897, s. 456.

14 Jacoby, Ergebnisse der Physiol., 1902, i, Abt. 1, s, 213.

15 Robinson, Brit. Med, Journ., 1891, aoe li, p. 1226; Nineteenth
Century, 1891, Buckman, ibid., 1894. Mumford, Brain, 1897, vol. xx.,

290.

. 16 Ahlfeld, Woaischrite fiir Ludwig, Marburg (1890), s.

1 Arbuthnot Lane, Guy’s Hospital Repoctas vol. xliii., oa p. 321; ibid.,
vol. xliv., 1887, p. 359.

18° MS Curdy, Amer. Journ. Physiol., 1901, vol. v., p. 95.

19 Tait Mackenzie, Journ. Anat. and Physiol., 1898, vol. xxxii., p. 468.

20 W, G. Smith, Proc. Physiol. Soc., Journ. Physiol., 1900, vol. xxv, ;
Mind, vol. xii., N.S., No. 45.

*1 Horsley and Schifer, Journ. Physiol., 1886, vol. vii., p. 96.

22 Schifer, Journ. Physiol., vol. vii., 1886, p. 111. Griffiths, ibid., vol. ix.,
1888, p. 39. Haycraft, ibid., vol. xi., 1890, p. 352. Fraser Harris, ibid., vol.
xvii., 1894-1895, p. 315.

* Warren Lombard, Journ. Physiol., vol. xiii, 1892, p. 1; vol, xiv.,
1893, p. 97.

*4 Pembrey and Todd, Proc, Physiol. Soc., Journ, Physiol., vol. xxxvii., 1908.

2 Henderson, Amer. Journ. Physiol., vol. xxi., 1908, p. 126.

% Zuntz and Schwmberg, Physiologie des Marsches, Berlin, 1901.

27 M‘Ourdy, Amer. Journ, Physiol., 1901, vol. v., p. 95,

28 Bowen, Amer, Journ, Physiol., 1904, vol, xi., p. 59.

- THE PHYSIOLOGY OF MUSCULAR WORK ~— 257

*® Pembrey and Todd, Proc, Physiol. Soc,, Journ, Physiol., vol. xxxvii., 1908.
% Gaskell, Journ, Physiol., vol, i., pp. 108 and 262; Journ, Anat, and
Physiol., vol, xi., 1877, p. 720.
*t Bayliss, Ergebnisse der Physiol., v. Jahrgang, 1906, s, 331.
_ * Schlesinger and Pembrey, Proc. Physiol. Soc., Journ, Physiol., vol.
xxxvii., 1908.
*% Haldane and Priestley, Journ. Physiol., vol. xxxii., 1905, p. 246.
* FitzGerald and Haldane, Journ. Physiol., vol. xxxii., 1905, p. 486.
% Haldane and Priestley, Journ. Physiol., vol. xxxii., 1905, p. 225.
% Geppert and Zuntz, Arch. f, d. ges. Physiol. Bonn, 1888, Bd. xlii., s, 189.
Loewy, ibid., s. 281; and 1890, Bd. xlvii., s. 601.
%8 Pfliiger, ibid., 1868, Bd. 1, s. 61.
3° Pembrey and Cook, Proc. Physiol. Soc., Journ. Physiol., vol. xxxvii.,
1908. Hill and Flack, Journ. Physiol., vol. xxxvii., 1908, p. 108.
_ © Schlesinger and Pembrey, Proc. Physiol. Soc., Journ. Physiol., vol.
Xxxvii., 1908. -
“1 Pembrey and Cook, ibid., p. xli.
*2 Pembrey and Cook, Proc, Physiol. Soc., Journ. Physiol., vol. xxxvii.,
1908, Oct. 17.
* Boycott and Haldane, Proc. Physiol. Soc., Journ. Physiol., vol. xxxiii.,
1905-1906.
Richet, Compt. rend. Soc. de biol., Paris, 1887, p. 482.
Pembrey and Nicol, Journ. Physiol., vol. xxiii., 1898, p. 386. Pembrey,
Arkle, Bolus, and Lecky, Guy’s Hospital Reports, vol. lvii., 1902, p. 283. In
these papers the literature of the subject is considered. Pembrey, Brit. Med.
Journ., vol. i., 1904, Feb. 27. Hill and Flack, Journ. Physiol., vol. xxxvi.,
) 1907-1908, p. 11.
“© Haldane, Journ. Hyg., 1905, vol. v., p. 494. Rogers, Journ. Royal
Army Medical Corps, 1908, vol. x.; p. 25. Sutton, Journ. Path. and Bact.,
1908, vol. xiii., p. 62. Pembrey, Guy’s Hospital Reports, 1902, vol. lvii.,
p. 261.

“ Pettenkofer and Voit, Zeitsch. f. Biol., Bd. ii., 1866, s.537. Sce Tigerstedt
Die Physiologie des Stoffwechsels, Handbuch der Physiologie des Menschen,
von Nagel, Bd. i., 1906, s. 441.

“8 Chittenden, Physiological Economy | in Nutrition, London, 1905. The
Nutrition of Man, London, 1907.
Zuntz and Schumberg, Physiologie des Marsches, Berlin, 1901, s. 311.
5° Collier, Brit. Med. Journ., 1907, vol. i., p. 4. Dunhill, ibid., p. 1031.

51 Hough, Amer. Journ. Physiol., 1902, vol. vii., p. 76.
*2 Hill and Fluck, Brit. Med. Journ., Aug. 22nd, 1908.
58 Weichardt, Arch. f. Physiol., 1905, s. 219.

SOME CHAPTERS ON THE PHYSIOLOGY OF
NERVE

By N. H. ALCOCK

I. Introduction. II. The Nerves in the Living Animal. III. Fatigue.
IV. Regeneration. V. The Theory of the Nervous Impulse.

I. INTRODUCTION

THE physiology of the peripheral nervous system has certain
peculiarities which too often deter the would-be student from
the study of the subject. The experimental facts are simple
and easy to understand, and have been determined with great
accuracy, yet the explanation is apt to be complex and lengthy
to a degree unusual even in physiology, and the task of mastering
the literature and understanding the various theories of what at
first sight appears far removed from any practical application is
one which is too often deferred indefinitely. It is a matter for
regret that this should be so, for the study of living tissues cannot
be separated into watertight compartments; no one subject can
be neglected without hindrance to the rest. The processes under-
lying the injury current of nerve are governed by the same
laws that determine the secretion of the salivary glands, of the
cells of the stomach or of the kidney, and it is only because
so much interest has been aroused about the obvious and
tangible results of the activity of these tissues that the under-
lying causes have for the moment been lost sight of. As soon as
one reflects as to the reason why a cell of the stomach sends
HCl in one direction rather than another, one comes across
problems that rest on the same physico-chemical basis as in the
apparently simpler case of nerve.

For those who demand an immediate practical advantage from ~
everything they read there is one comparatively minor considera- _
tion that may perhaps appeal. The charlatan and quack, ever
with us, take advantage of the prevailing neglect of electro- |

258

'
;
|
|

THE PHYSIOLOGY OF NERVE 259

physiology ; it is hardly necessary to quote the instances of
electropathic battery belts, the claim that nerve contracts on
excitation (1), and the “records” of the electrical response in
metals (*), to show that folly of a kind that one moment’s reflection
should dissipate finds a ready acceptance with those who consider
the experimental facts of animal electricity too dull for their
enlightened minds.

There is, however, one quite genuine difficulty in the study of
our present subject that makes it less interesting than it will be
in the future. None of the theories are in any way complete, and
we come across many facts which appear to conflict with the best

arranged of these explanations. All that can be done in such a

case is to record these facts in the hope that later on the proper
place may be found for them; the simple and easy receipt for the
manufacture of hypotheses by the inclusion of favourable instances
and the exclusion of everything that contradicts the theory is one
that does not lead to a result on which much reliance can be
placed.

PRELIMINARY NOTES

It is unnecessary to do more than briefly recapitulate the
experimental facts that have been made out concerning excised
medullated nerves that are still in a surviving condition, yet as
they form the starting point of what follows it may not be
out of place to give a short summary of the most important
phenomena.

After the nerves have been excised from the body they are
best kept in an approximately isotonic solution of NaCl, to which
a small quantity of glucose may with advantage be added. When
the effect of the excision has passed off, such nerves are isoelectric,
that is, they give no current in the galvanometer, and they have
apparently (except in certain known particulars) resumed the con-
dition they were in before they were removed from the body.

Three main varieties of electrical phenomena directly connected
with function can be observed in such nerves—(1) Current of
injury; (2) current of action or negative variation; (3) electro-
tonic currents; giving to each the usual name. Excellent reasons
can be given for the disuse of each of these terms, but as their
significance is perfectly clear, it seems better for our present

_ purpose to use words with which the student is already familiar

260 SOME CHAPTERS ON THE

rather than introduce confusion by the employment of theoreti-
cally more perfect but unknown expressions.

The explanation of these terms is simple. If in an isoelectric
nerve an injury be made at any point, that spot becomes electrically

Qu Zn
+ —_
LL NS SS
() <— ()
FF Qurrent of injury.

negative (zincative !) to the uninjured part, and this difference of
potential gives rise to the current of injury (Fig. 1).

If such an injured nerve be excited, the uninjured part also
becomes electrically negative (zincative), and as this gives rise to

ee

Fig IL a a pa GIO PO Og pO gO pg OOD gnc

a+ ——— —" pe

Figl= eee Sa
Ewcit: action.

an opposing current to the current of injury, the latter appears to
be diminished, and therefore the result is to produce a diminution
or “ negative variation ” of the injury current (Fig. 2a). . i
If an uninjured nerve be excited, the normal effect is that a
wave of zincativity passes down the nerve, each point becoming —

1 Like the zinc of a Daniell cell.

PHYSIOLOGY OF NERVE 261

successively electrically negative (zincative) to the rest. This has
been termed the current of action, and the negative variation is
evidently only a particular case of this, namely, when the response
from one spot is altered by the presence of an injury there (*),
neglecting for the present certain possibilities to be considered
later.

These remarks can therefore be summarised thus :—

(1) Any injured spot is electrically negative (zincative) to any
uninjured.

(2) Any active spot is as a rule electrically negative (zincative)
to any inactive spot. ©
_-- Injury and excitation give, therefore, as a rule, an electrical
response of the same sign. Whether this is the result of the same
process or not is a matter that is not quite as simple as at first

> ——

Fig IL LOLOL A AL AD LA AL AL AL AL AL ALAA AAPA OPO” OPPO OL a oo

q D q (perewe
\
ee a er,

sight might be supposed, though there is undoubtedly a close
| connection between the two responses.

| pete i"
|
|

There is still another phenomenon to be noted in excised
medullated nerve. If a constant current be passed through one
part of the nerve, the extra-polar parts of the same nerve also give
a current, the electronic current (Fig. 3).

These various electric effects have been subjected to elaborate
investigation and experiment, because they are the only direct
unequivocal signs of nerve activity. The actual metabolism of
nerve is at best very slight in amount. It is true that deprivation

- of oxygen for some hours paralyses a nerve (* ® 7), that the result
of excitation gives an effect similar to that of CO, (§), and that
experiments to be noted later give some indication of fatigue,
but there is no detectable change in the reaction of nerves_as a
result of activity (unless certain experiments referred to later are
to be interpreted in this sense), and there is no other effect such as

_ that of heat produced or of mechanical shortening? that shows

1 If a nerve is excited at one end by maximal induction shocks, and the
; other end examined with suitable precautions under a microscope magnifying 200
_ diameters, no shortening or movement of any kind can be detected. But Waller

262 SOME CHAPTERS ON THE

whether a nervous impulse is passing or not, so that the electrical
signs of nerve activity have assumed a greater importance than
is the case in the physiology of other organs of the body. Further,
these effects, occurring in such a highly specialised structure as
nerve, have seemed a suitable object for the attempted explana-
tion of many problems of general physiology. It becomes then
a matter of great interest to see how far these electrical effects
observed on excised nerve represent the events occurring in nerve
still in the body, especially as evidence has been brought forward
to show that it may be possible, under exceptional circumstances,
to have a nervous impulse without the corresponding electrical
change (*).

II. NERVES IN THE Livinc ANIMAL

The first of the modern instances we shall quote is from the
work of Gotch and Horsley (*). In this there is one series of
experiments that bear on this question. In the cat and the
monkey both the sciatic nerves and the cut end of the spinal cord
gave unmistakable evidence of a negative variation which accom-
panied the excitation due to the reflex discharges from the
nervous centres when these were excited by absinthe or (more
markedly) by strychnine. Negative variations produced in this
manner corresponded exactly with those produced by the electri-
cal excitation of the cortex and other parts, and except in so far
as the nerve impulse might be altered centrally by the drug
(Sherrington !), these variations represent the results of the
normal excitation of the nerve fibre by the nerve cells.

Bernstein (14) in 1898 observed a similar phenomenon. If a
pithed frog be lightly strychninised, the muscles of the hind legs
fall into tetanus whenever any stimulus reaches the spinal cord.
These tetanic contractions are more or less synchronous, and if
by a modification of Bernstein’s method one of the legs of the
frog be connected with a myograph, and the sciatic nerve of the
other be placed on electrodes, and connected with a galvanometer
or electrometer, it can be easily seen that when there is a con-
traction of the muscles there is a negative variation in the sciatic
has shown that if strong induction shocks are \passed lengthwise through a nerve
(or any other moist conductor), that the heating effect of the current produces

either lengthening or shortening, according as evaporation or rise of temperature
predominate. .

‘iz

;

a

PHYSIOLOGY OF NERVE 263

nerve. The reflex contraction can be called out by stimulating an
afferent nerve by the induced current, or even by the impulses
reaching the cord as a result of touching or pinching the animal.

The E.M.F. of the negative variation is about *00025 volt, as

determined by the capillary electrometer (!*).

It is possible to take a step further and examine the negative
variation in nerves which are conducting the impulses which
naturally traverse them without the complication of any disturb-
ing agency. Two nerves have been employed for experiments of
this kind, the phrenic and the vagus. Both these conduct im-
pulses which are repeated at each act of respiration, and so it is
possible to arrange the rather elaborate apparatus required with
some degree of certainty of obtaining the phenomenon often
enough to be readily investigated. Reid and Macdonald (!%) ex-
amined the phrenic ; Lewandowsky (14), Aleock and Seemann (!”),
and Einthoven (!5) the vagus. The latter is by far the easier object
to study, and allowing for the increasing delicacy of the instruments
employed, the results agree very closely as far as the nervous
phenomena are concerned.

Lewandowsky, using the ordinary galvanometer, found that one
negative variation occurred every time the lungs were artificially
blown out. Alcock and Seemann, with the capillary electrometer,
observed the same phenomenon. They found in addition that a
negative variation occurred at each natural inspiration, and that
an effect was also observed when the air was sucked out of the
lungs. Einthoven, using his string galvanometer, by far the most
sensitive instrument yet invented,’ was able to add certain very
interesting details which are worthy of careful consideration.

Einthoven’s results will be understood from an examination of
Fig. 4. The upper line is the shadow of the “string” (a fibre

_ 3 This galvanometer consists of a fibre of silvered quartz, about 2°54 in diameter,
suspended in a powerful magnetic field (20,000 C.G.S. units). The fibre is illuminated
by the light of the electric arc, and the shadow of the fibre, magnified 600 diameters,
is thrown on a photographic plate. The instrument is thus a ‘‘ moving coil”
galvanometer, with the coil reduced to its simplest expression. When a current
of electricity passes down. the fibre, it is deflected, and 10-* amperes give a
measurable deflection. P

The instrument therefore measures current not voltage ; but if the resistance of
the circuit is known, the voltage can be determined very simply by Ohm's law. In
nearly all electro-physiological problems it is the E.M.F. that is of interest, as the
resistance and consequently the current is varied by circumstances not bearing

on the experiment.

264 SOME CHAPTERS ON THE

of quartz silvered on the surface), moving up and down according
to the current traversing it;

eee 228i 84
a : = & the second line indicates the
tit HS : = 6 respiration, inspiration mark-
; £2 ing upwards. A slow wave
Suerte sects =3 of negative variation occurs
: ase *= at each inspiration (indicat-
ae ing that an impulse passes
sess aH if oe up the nerve at this time), a
desea 2= conclusion arrived at on quite
“© other grounds by those who
Be: < HHH 23 have observed the pheno-
: 38 menon of respiration.
: : HY 5 There are many things of
fps racesectetereeeesed Hy % interest to be observed in
Bisse. soccer rssesee +] =£ studying this photograph. In
Hh ce the first place, the curve is
rH 2 3 Z a double one; superposed on
gee a: +7 22 the long respiratory waves
: HH 3 Bs are shorter ones, the result
z HE gE ae of the contractions of the
se: HH 42 2 heart. Secondly, to any one
ieees HHH 22° used to the study of the
: Hit] ~ = & negative variations recorded
Suess sees ‘22. by the capillary electrometer
at 22% two differences are most strik-
: +H 5 72 ing—the E.M_F. of the current
BES and the time taken by the
; 222 wave. In Gotch’s (**) analysis
Sih HERS T we of the electrometer curve the
: gue E.M.F. of the negative varia-
sists : #8 tion in the sciatic of the frog
fesatetae. ts sass: /B8e2 is ‘03 volt and the time
HTH "=". -Ol sec.; here the E.M.F. of
fipseeticsceesttitess é Be the respiratory curve is
aH = 5
: EE tg 00005 volt and the dura-
@4 S58 tion 5 secs. The question
: ar & immediately presents itself—
ae : sa

Are these phenomena, which
alike have been callect “‘ negative variation,” in reality the same ?

PHYSIOLOGY OF NERVE 265

One possibility may be dismissed from the mind. As far as
our present knowledge goes, these curves are not current escape
or any error of the apparatus. They are abolished by ligature of
the nerve, by touching the nerve with ammonia, and by “ electro-
eution.” If the peripheral end of the other vagus is stimulated,
the cardiac waves disappear, as the heart is stopped, while the
respiratory waves continue, as can be seen in Fig. 4. In apnea,
the cardiac continue and the others cease.

Both the E.M.F. and the time relations of these curves agree
with the older observations with the electrometer. Alcock and
Seeman (loc. cit.) give the E.M.F. of the respiratory response

as ‘00005 to -0002 volts, and the time as about 4 secs.; the
maximum on prolonged inflation of the lungs as 00025 volt.

What, then, is the explanation? The differences in potential
may be due (and to some extent are certainly due) to the fact
that only a few of the fibres of the nerve are in action at any
one time, but how is the difference in time to be accounted for ?
There are several possibilities. These long waves of small E.M.F.
might be the algebraic sum of many short waves; and if we had
the electrometer records alone to go by, these might be too slow
to indicate the successive teeth of such a curve. But there is no
trace of such a summation in the string galvanometer photograph,
although the instrument is sensitive and quick enough to detect
‘000005 volt lasting for the ;}; of a second. Further, this instru-
ment is free from the peculiarity of the electrometer that shows
the effect of equal alternate currents of short duration as a dis-
placement of the meniscus in the direction of the sulphuric acid.
The exact relation of these two phenomenon which we have called
by the name of negative variation is therefore one of the pro-
blems still awaiting solution, and we have only the suggestion

- by Einthoven that possibly his curves are more nearly related to
the electronic currents than to the short steep curves the result
of single induction shocks, that Gotch has analysed in the sciatic
of the frog. | ;

Einthoven finally gives a very interesting photograph showing
the variations in potential in the wninjured vagus as a result of
the various nerve impulses passing both up and down the nerve.
The exact analysis of the course is, however, so complex that we
must await the result of future work before we understand the

_ full meaning of the photograph.

266 SOME CHAPTERS ON THE

III. Faticue

The apparent absence of fatigue in nerve, which is one of the
earliest phenomenon that the observer meets with and the student
hears discussed, is philosophically considered a very curious pro-
perty of these structures, and has both a greater importance and
a ‘closer connection with what has gone before than might at first
sight be supposed. The fundamental experiments are known to
every one. Medullated (17 1® 1%) and non-medullated (7°) nerves
can be stimulated for hours, the impulse being blocked (by cold,
ether vapour, the constant current and so forth), and when the
block is removed the end organ responds to an amount apparently
identical with that with which the observation began. As far as
this class of experiment goes, no fatigue can be detected, and —
even in isolated nerve, completely removed from any possibility
of the natural circulation being maintained, Waller (*) has shown
that fatigue is not found.

Various explanations could be found of this result. The most
obvious, that as no fatigue can be detected there is in reality none,
would be, if true, a most remarkable phenomenon. It would
mean that a nervous impulse was conducted along a. living
structure, that connected with this was an electrical change of a
measurable amount, and yet that no energy was made use of in
the process, a phenomenon unlike any other occurring in the body.

The next explanation, and the one that seems the most pro-
bable, is that although there is a certain amount of fatigue, and
a certain expenditure of energy, that the loss is very quickly made
good, and the process of repair is so rapid? that even between
induction shocks following one another at 500 per second (and none
of the induction coils used for the first class of experiment ran
at anything like this rate) there is time for the nerve to recover
its initial state.

There arose at one time a curious little controversy of which
a short account may not be out of place. Waller (*) made the ~
suggestion that the rapid repair just referred to might be due to
the medullary sheath acting as the storehouse of reserve material,

1 Other examples of very rapid repair of tissues that admittedly show fatigue
could be quoted. For example, the wing muscles of insects contract about 300

times per second, and continue in action for hours at a time, yet no one imagines
that they are incapable of fatigue on this account.

PHYSIOLOGY OF NERVE 267

and therefore that non-medullated nerve not possessing this store
should prove much more easily fatiguable. Miss Sowton (?"), using
the olfactory nerve of the pike, stated that this was the case ;
but she omitted to exclude the possibility of the so-called “ stimu-

lation fatigue,” that is, the local injury at the spot where the

exciting electrodes rested. Garten (**), in his classic researches on
the same object (of which only very brief and incidental mention
can be made here), excluded this possibility, and found that true
fatigue of the conducted negative variation actually occurred, re-
covery taking place after a suitable interval, even in excised nerve.

The objection might be made that the olfactory nerve of the
pike is not comparable to mammalian nerve, and certainly in the
latter “stimulation fatigue” is more easily observable than that
of the propagated change (**), but it is probable that the difference
that exists is one of degree rather than of kind. It would be
interesting to try the experiments quoted in the next section on
non-medullated mammalian nerve ; the probability is that fatigue
would be demonstrated even more readily than in the medullated
variety. It is not unlikely, therefore, from these and other reasons
to be presently referred to, that the structures known as sheath
(including under this heading medullary sheath and neurilemma)
act as stores of food material, and this does not exclude the idea
of Boruttau, that the Cae substance may also function in
this capacity.

There is, however, a more indirect way of approaching the
question that has led to very interesting results. If there is any
expenditure of energy in transmitting a nerve impulse, a second
impulse rapidly following the first should show some alteration.
This is found to be the case.

Gotch and Burch ('*) examined the electrical response in the

_ sciatic of the frog, when this was excited by induction shocks.

If these succeeded each other at longer interval than ,1, of a
second (taking round numbers), two negative variations were
observed ; if the interval were less than this, only the response
due to the initial stimulus appeared, and the time short enough
to abolish the second response was termed by these authors the
“ critical interval.” They found that this varied with the intensity
of the exciting stimulus and with the temperature of the nerve,
becoming longer as the temperature grew less. Stated differently,

_ this “ critical interval” is the “ refractory period ” of the nerve.

268 SOME CHAPTERS ON THE “?

Frohlich made a further advance, though before his results can
be considered in this light it is necessary to make a very important
assumption, viz. that the effect of anesthetics (ether, chloroform,
&c.) is the same as that of cold, and that the lengthening of
the “critical interval” or “refractory period” due to all these
agents is merely a slowing down of the processes occurring in a
normal nerve in the body.

If this is granted, Fréhlich’s experiments formed a very interest-
ing example of fatigue. He took a nerve which was in a definite
state of anesthesia, and stimulated this with induction shocks
which followed each other at an interval known to be a little
longer than the “critical interval.’ The attached muscie served
as the indicator. When the nerve was excited the muscle at first
fell into tetanus. This is only what might be expected ; the suc- |
cessive stimuli each gave rise to a separate impulse, and thesé
fused at the muscle. But as the excitation continued, the tetanus
very rapidly fell off, and the muscle ceased to contract, and
Fréhlich’s explanation is that the successive impulses fatigued
the nerve, so that the refractory period became longer, the rate
of stimulation was now less than the critical interval, each exci-
tation blocked the next, and so no impulse was propagated to
the muscle. Tait and Gunn (74) have extended these observations,
using Yohimbin lactate as the anesthetic. They find that this
substance has in some respects the same action as other anzs-
thetics, and they are able to confirm Froéhlich’s results and add
some interesting details. There is little doubt, therefore, that
under the action of reagents of this class nerve shows fatigue (and.
in all probability Waller’s (2 26) experiments with proto-veratrine
and aconitine come under this heading), and if the preliminary
assumption be accepted, it could be deduced from these observa-
tions that nerve fibres even in the body are fatiguable,’ and
only do not show this property under ordinary conditions because
the processes of repair are so rapidly carried out (?’).

IV. REGENERATION OF NERVE FIBRES

The effects of section of a nerve are known to every student,
and there is a general agreement amongst those who have experi-
mented on the subject as to the nature of the process. This may

1 For a different method that also leads to this conclusion, see Thérner (?%).

°

De E——— Ke SSrtci‘(i( ‘trl

PHYSIOLOGY OF NERVE 269

be briefly summarised as consisting of the degeneration of that
part of the nerve fibre which has been cut off from the appropriate
nerve cell. Whether the “ neurone theory” is anatomically exact

or no, as far as this particular physiological problem is concerned,

the degeneration exactly follows the law.

There is no such unanimity as to the events occurring subse-
quently. Under certain circumstances, to be considered shortly,
the degenerated part of the nerve fibre is regenerated, and the
particular point on which controversy has arisen is the source of
the new nerve fibres.

There are three possible ways in which such fibres might
arise.

I. They could grow downwards from the central end of the
divided nerve, as Waller originally described in 1850.

II. They could be formed in situ from the cells in the peripheral
portion, and then grow up towards the spinal cord.

III. They could wander in from the central end of other cut
fibres, to which they originally did not belong.

Each of these possibilities must now be considered.

I. While this source of the new nerve fibres is regarded by

_ most observers as at least the usual one, it must be remembered

that there are certain conditions which must be fulfilled before
regeneration can take place in this manner.

(a) The peripheral and central ends of the divided nerve must
be brought into some sort of connection. This is usually done
by apposition and suture of the two cut ends; but where there
has been loss of nerve substance, and a gap is left, this can be filled
by another nerve from the same individual, which is naturally the
best method, or failing this, by the interposition of some other
tissue. This can be either plain catgut, or a nerve from an-
other animal, the results are about equally good in both cases
(Kilvington *8), and Marinesco (**) has shown that an alien nerve is
absorbed™s a foreign body and presents no advantages over catgut.

(b) The negative side of the condition is interesting. If the
cut end of the peripheral part be enclosed in a rubber cap or
stitched to some part of the body where nerve fibres are scarce,
such as the peritoneum (*), no regeneration occurs at ali. This is
one of the arguments against the growth of the new fibres from
the peripheral end, as we shall see presently.

(c) The portion of the spinal cord from which the nerves

7

270 SOME CHAPTERS ON THE

originated must be intact, for if this is excised no regeneration
follows (Lugaro *),

(d) In the case of the posterior nerve roots no regeneration
takes place after the nerves have entered the spinal cord, and this
corresponds with the anatomical fact that here the nerves lose
their neurilemma. The inference is that the presence of this
structure is therefore necessary in some way for the growth of
new fibres.

(e) There must be a fresh section of both ends of the nerve,
for if a cut end is sutured to an uninjured longitudinal surface,
no regeneration takes place (Kilvington 8),

If these various conditions are fulfilled, the evidence that down-
growth takes place from the central end is very good.

Ramon y Cajal and Marinesco (**) figure the new fibres growing .

downwards ; these are at first seen only in the neighbourhood of
the suture, and gradually grow towards the periphery. The fibres
are often quaintly twisted, and the bulbous end shows curious
shapes which are probably the result of amceboid movements.
The new fibre seems to seek the old path by some force of chemio-
tactic attraction (*°). The medullary sheath is formed first at
the central end, later at the periphery, so that the former is the
oldest part of the new fibre. If a second cut is made, either
central to the line of suture (Langley and Anderson *) or _peri-
pheral to this (Halliburton), degeneration again takes place, but
only in the peripheral part of the new fibres.

Finally, the embryological evidence is in favour of the central
origin of the fibres, though it must be remembered that this
evidence is only available by making use of the assumption that
the regeneration is carried out by the same process as began
the growth in the embryo. Ross Harrison (*® #°) has verified
on various species of Rana, the original observations of His,
that all the parts of the nerve fibre grow outwards from

the cells of the epiblast that form the neural ridge, and that —

this is true not only for the axis cylinder, but also for the
medullary sheath and neurilemma, in this latter particular con-
troverting Bethe’s statements, referred to in the next section.
Harrison actually observed under the microscope in parts of
- embryos kept alive the outgrowth of new fibres from the’ neural
crest. Each fibre had a swelling at the free end like that of a

regenerating nerve, and this swelling showed amceboid movements.
od

al

|

PHYSIOLOGY OF NERVE 271

There was no growth of any structure such as neurilemma from
any other part of the embryonic tissue, though the conditions
were sufficiently good to permit of the development of striated
muscle from mesoblastic cells. Harrison further localised the cells
that gave rise to the anterior and posterior nerve roots; if the
back of the neural crest were cut away the latter did not develop ;
if His’s cells were excised the anterior nerve roots did not appear.

II. Regeneration from the peripheral end.

The evidence for this view would be much more satisfactory
if the third possibility to which we have referred did not exist.
Briefly, there are three points to be considered :—

(a) The growth of new fibres when the central end of the cut
nerve is no longer a possible source.

(b) The rapid return of sensation after section.

(c) Embryological and histological evidence.

(b) Kennedy (*) and others look on the rapid return of sensa-
tion (in a few days in some cases) as evidence of peripheral
regeneration. But Head (* * 4) has shown that the measure-
ment of returning sensation is by no means as simple as was at
one time supposed, and when the various explanations in any
given case have been disentangled there is very little left on which
to found a theory of autogenetic regeneration. Head’s experi-
ment on himself gave no support to this view, and here it was
possible to make more precise observations than had hitherto been
the case.

(c) Bethe’s (47) embryological researches led him to the con-
clusion that before the appearance of any trace of peripheral nerve
fibres a band of spindle-shaped cells can be seen in the place where
the nerve is to be found. These cells were supposed to combine
to make a syncytium, producing by differentiation of their proto-

- plasm the neuro-fibrils of the nerve fibres. Braus (*), as a result

of his very ingenious transplantation experiments on tadpoles, came
to a somewhat similar conclusion ; but as both these authors are
directly opposed to Ross Harrison in their explanation of their
observations, it is only possible to say that the experiments of
the latter seem, with our present knowledge, the more worthy of
credence.

Mott and Haliburton (*4), and later Graham Kerr (**), have
shown, however, that in the process of degeneration certain changes

_ take place in the peripheral end of the nerve that simulate the

272 SOME CHAPTERS ON THE

growth of new fibres. The cells of the neurilemma multiply
actively. They first act as phagocytes in removing the debris of
the degenerated nerve, and then elongating, form themselves into
long chains of cells ; but if no nerve fibres enter these chains, they
never, as far as can be seen, form either medullary sheath or axis
cylinder. So that although these neurilemmal cells doubtless have
important nutritive and other functions (we have already referred
to the suggestion that the failure of regeneration in the spinal
cord is due to the absence of the neurilemma), yet by themselves
these neurilemmal cells do not form new nerve fibres.

III. The third possibility, that regeneration may occur from
new fibres which wander into the cut peripheral end from an alien
central end, is one that gives rise to many interesting questions.

It has been known for a long time that intentional suture of .
nerves originally distinct leads to regeneration, but even when
actual suture is not performed, growth may take place if there
are any cut nerves in the vicinity, and it is occurrences of this
description that invalidate much of the evidence for autogenous
growth, as has been explained in the previous section.

There would appear to be degrees in the chemiotactic attrac-
tion which determines the direction of the fibres; efferent somatic
fibres unite most readily with their own kind, less readily with
pre-ganglionic fibres, and apparently not at all with post-ganglionic
fibres (5). Of the various possibilities of union thus summarised
there is one which has attracted special attention, as it has an im-
mediate bearing on surgical procedure. This is the particular case
in which different efferent somatic fibres are made to unite with
each other. Ballance (°°) was the first to make a practical applica-
tion of the fact, although he did so under the impression that
regeneration would occur from the peripheral end. He sutured
part of the spinal accessory nerve to the peripheral end of the
facial, and in his most successful case the patient recovered the
use of the paralysed facial muscles, but with the drawback that
there was a synchronous lifting of the shoulder.

Kilvington (28) has studied the experimental conditions under
which union of this class takes place, and two of the many
interesting facts he observed may be noted.

The optimum arrangement, as judged by the functional recovery
of movement, is shown \in Fig. 5. Here the internal and external
popliteal nerves are cut\across, the central end of the external

PHYSIOLOGY OF NERVE 273

popliteal turned up out of the way, and the central end of the
internal popliteal slit up lengthwise for a short distance. The
peripheral ends of both nerves are then sutured to the two parts
___ of the central internal popliteal.

' ——s'It is found that regeneration takes place, and after the
appropriate interval the dog has the use of his hind limb with
little or no apparent defect, and such delicate co-ordinated move-
ments as the scratch reflex are performed to all appearance as
£ well as in the normal animal. Kilvington infers that the fibres
from the internal popliteal have grown downwards into both

LP EP Le.) Er

1 (8 U

|

IP E.P : IP EP

Fic. 5.—Optimum arrangement for Fic, 6.—Arrangement giving ‘‘ axon
restoration of function. J.P. Internal reflex.”
and £.P. External Popliteal nerve.

internal popliteal and external popliteal. If this inference is a
just one, it follows that the muscles formerly supplied by the
external popliteal (and from the corresponding cells in the anterior
horn of the spinal cord) are now supplied from cells that formerly
supplied the internal popliteal, and through the nerve trunk the
antagonistic muscles. As the: co-ordination seems as good as
before, the cells that have been changed over must have learned
a new lesson, and this apparently applies, not only to the cells
in the spinal cord, but also, as Kennedy (**) has shown, to the
cells in the Rolandic cortex.

The earlier experiments of Langley and Anderson and Kilving-
ton, and the later of Kilvington and Osborne, provide another
fact. If the connections at the time of suture were arranged as

s

274 SOME CHAPTERS ON THE "i

in Fig. 6, that is, if the central end of the internal popliteal was
simultaneously sutured to both external and internal popliteal
together, then when regeneration has occurred three points are
noted. (Langley and Anderson observed a similar phenomenon
when the central end of the crural nerve is sutured to the in- |
ternal saphenous and also connects with its own muscular branch.)

(1) Co-ordination is nearly as good as in the normal animal.

' (2) There are more new fibres in the two branches than in the
central trunk.

(3) Excitation of, e.g., the peripheral end of the regenerated
external popliteal, gives a contraction of the muscles supplied by
the internal popliteal; even when all connection with the spinal
cord is removed by section some distance above the line of suture.
This contraction is termed the axon reflex, following Langley’s
terminology. .

Some of the new fibres in the trunk must therefore have a
double peripheral ending in the branches. The inference is that
either the peripheral fibres have joined together, which is a
process unknown elsewhere, or else that one central fibre has
branched into two at the line of suture. The latter explanation
is by far the most probable. The inference is that in this case
antagonistic muscles must be to some extent at least innervated
from the same anterior nerve cells. It is surprising, not that
co-ordination fails in the finer details, but that it exists at all
under these conditions.

V. THEORIES OF NERVE ACTIVITY

It is not possible to review, in the compass of a work of this
kind, one-tenth of the literature that exists on this subject. All
that can be done is to select such portions as seem worthy of con-
sideration, not so much for their intrinsic worth as for the indica-
tion they give as to the direction in which further researches will
advance.

From the physico-chemical standpoint all the phenomena of
the electric currents in nerve (and in all tissues) must be due, as
far as our present knowledge goes, to the movement of ions carry-
ing charges of electricity. Current of injury, negative variation
and electrotonic currents, must all ultimately have this explana-
tion ; and as no other hypothesis seems at present at: all probable, ‘

Ve ——

~ of Macallum (

—_— —

PHYSIOLOGY OF NERVE 275

the work of the electro-physiologist has received an entirely new
direction, namely, that of endeavouring to see how the laws of
solutions and electrolytes can be applied to living tissues. The
problem is by no means a simple one. The nature and composition

‘of the ions has to be determined. They might be either inorganic

electrolytes such as KCl, or more complex bodies such as occur in
the products of digestion. They might be present in the tissues
as such, or be formed by chemical action and then appear, and
their distribution may be controlled by semi-permeable membranes,
or by surfaces of separation which would act in a similar manner.

Before considering the modern theories of nerve action it will
be convenient to note briefly the result of the micro-chemical work
51, 8, 54) which has greatly influenced the theoretical
view of the subject in this country.

Of these papers, two deal with the subjects with which we
are now concerned, namely, the determination of (1) potassium
and (2) chlorides in cells and nerve fibres.

(1) To determine the potassium (51) fresh nerve fibres are placed
in a solution of cobalt sodium hexanitrite (Co,Na,(No,),) ; where
potassium is- present, a precipitate is formed. According to
Gilbert (°*) its formula is (Co(No,), 3(K/Na)No, nH,O). The
excess of the reagent is washed away with ice-cold water, and
the precipitate blackened with ammonium sulphide. Macallum
found a precipitate in the medullary sheath where the neuro-
keratine network is supposed to exist, in Lanterman’s imbrica-
tions, at the nodes of Ranvier, but not in the axis cylinder. Even
at the nodes of Ranvier, where the precipitate surrounds this:
structure, the axis cylinder itself is free.

(2) The distribution of the chlorides (5 5) was investigated by
the addition to the tissues of y'5 normal AgNo, solution con-

_ taining 15 per cent. HNo,. The result is briefly the reverse

picture of the potassium. Chlorides are absent from the medullary
sheath. They are present all along the axis cylinder whenever
the reagent can penetrate, either at a node of Ranvier or an
injured spot. Lantermann’s imbrications are an exception: K
and Cl are both found there.

Taken as they stand, Macallum’s researches would show that
in what is presumably the active part of the nerve, namely, the
axis cylinder, chlorides were present in greater amount than in either
the lymph outside or in the medullary sheath, while potassium was

present in the latter but not in the axis cylinder. Macdonald
has given a different explanation of these results, but it is not
improbable that the original view is the more correct.

We are now in a position to consider the bearing of these
observations on the theory of the nervous impulse. All the
modern workers agree in supposing that the dissolved electrolytes
are the cause of the electric currents, but as to the details of the
process each experimenter has a different view, and the more the
details are considered the less probable any given theory appears,
so that a very brief account here will be sufficient.

In general, it is possible that the currents can be caused by
any one of three different processes.

I. Chemical cells, of which the familiar type is the Leclanché.

II. Concentration cells, where the current is caused by the
diffusion of ions with different velocities from a place of high
concentration to one of lower.

III. Fluid cells, where the current is caused by the interchange
of the ions of two fluids separated by a membrane.

I. The chemical-cell theories present more difficulties in the
case of nerve than the other two, and in spite of the distinguished
men who have been advocates on this side the general opinion is
now rather adverse to this view. It is quite unlikely that there
are no chemical changes in nerve. But the small amount of nerve
metabolism, the difficulty of showing any change in this meta-
bolism as a result of activity, and the apparent absence of any
heat produced, are all observations which tell against the proba-
bility that chemical activity is directly concerned with the nervous
impulse.

One series of observations, however, can be taken as supporting
the chemical view, namely, those on the temperature coefficient.
It has been observed that the rate of change of a physical process
is less altered by variations in temperature than that of a chemical
one—in other words, that the temperature coefficient given by the
velocity at (T° + 10)

velocity at TS
case, more than this in the latter.

Maxwell (°°) has for this reason carefully measured the velocity
of the nervous impulse at different temperatures. He took the |
pedal nerve of the giant slug (Ariolimax Columbianus) as the
object, and although the observations are not easy even in this

,

276 SOME CHAPTERS ON THE

equation , is usually less than 1:2 in the former

PHYSIOLOGY OF NERVE 277

comparatively favourable object, it is probable that Maxwell’s
mean value of 1°78 is sufficiently near the truth, and Keith Lucas (**)
as a result of observations by a different method on the frog gives
a mean value of 1°79.

This is definitely higher than the usual physical value of 1:2,
and might be taken as indicating a chemical basis of nerve con-
duction if one could be certain (which is very far from being the
case) that a tissue which contains loose combinations of electro-
lytes with proteins would not have a similar coefficient. At any
rate Keith Lucas shows that the value 1-78 to 2°01 is very nearly
the same for conduction in both nerve and muscle, and markedly
different from that of 3°26 to 3:6 for the refractory period in
both tissues (5” 5), so that the underlying processes are probably
different in the two cases.

Maxwell makes the suggestion that if nervous impulse is a
chemical process it is probably not a direct oxidation, as if it were
the coefficient would be higher. This would agree with the absence
of heat produced. But we can hardly pursue the subject further
in the present state of our knowledge, though it presents interesting
problems that further work may solve.

II. Concentration Cells—Macdonald (5°) has adopted this theory
of the causation of the nervous phenomena, and as he has based
his views on a long series of ingenious experiments, they merit at
least a careful examination, even if his conclusions are not accepted
in every detail. Adopting the same plan as before, and separating
experimental facts from the inferences therefrom, Macdonald’s ©
work may be summarised as follows:— __

(1) The specific resistance of nerve (sciatic of cat) is 180 ohms,
approximately equal to ‘3 per cent. NaCl.

(2) When a nerve is placed for a short time in a dilute

‘solution of electrolytes, the injury current is increased ; in a strong

solution it is diminished. In the particular case of chlorides this
alteration follows the “ concentration law,” namely—

E,, = Ee x log F
where E,,=the final E.M.F. after immersion.
E,=the initial E.M.F. before immersion.
n=the concentration of the solution in gram-molecules per litre multiplied
by the dissociation coefficient.

(3) The inference is drawn from these and other considera-

278 SOME CHAPTERS ON THE

tions that a nerve fibre has a structure consisting of a “core”

containing a concentrated solution of electrolytes, a semi-permeable
membrane outside this, and outside the membrane a “sheath”
containing dilute electrolytes.

(4) From the concentration law E,=E, x log va calculation
can be made of the concentration of electrolytes in the core. For
when n=1, then as log 1=0, E, =0, therefore a solution of T

(dissociated) MCl would cause the injury current to vanish, and
would presumably be equal in E.M.F. to the solution of the
electrolytes in the axis cylinder. If these consist of KCl, this
concentration is nearly 10 per cent.

(5) The conductivity of this solution in the axis cylinder can
also be calculated, if this conductivity of the whole nerve is known,
if the relative amounts of axis cylinder, sheath, and connection
tissue are estimated, and if the conductivity of the sheath be
supposed to be the same as that of the solution in which the nerve
is placed for a short time. Macdonald gives the value from these
data as equal to 2°5 per cent. KCl very approximately.?

(6) Under the microscope the axis cylinder of a living tissue
is clear and transparent.? At the injured end granules are seen,
and these stain with neutral red. These red-stained granules
gradually appear further and further down the nerve, and the
rate of appearance varies as the concentration of the fluid bathing
the fibres, being -17 x 10—° cm. per second for 2 NaCl, :30 x 10-°

m

for 55 NaCl. Macdonald infers that this process gives a graphic

representation of the diffusion of the ions causing the injury
current. Toluidine blue gives a rather different appearance which
may represent the action current.

(7) Macdonald agrees with Macallum in his picture of the
distribution of chlorides in the axis cylinder, but disagrees as to
the distribution of potassium. He declares that while potassium

1 Some unpublished experiments indicate that this value may require revision.
The strength of solution in which the sciatic nerves of the cat remain unaltered in
weight is 1°16 per cent. NaCl (°°).

2 All authors agree with this. If the fibre is fixed different appearances are —
seen ; that usually accepted as the best shows longitudinal fibrils in.a clear or —
granular matrix. Ashworth (*'), examining the giant nerve cells and fibres of Halla
parthenopeia, where these appearances are very distinct, finds quite definite fibrils,
arising from the nerve cell and continued into the nerve fibre. If the nerves in
the animal resemble those in the frog, this observation supports the usual view. -

e

PHYSIOLOGY OF NERVE 279

is invisible under ordinary circumstances, the black precipitate is
invariably obtained in the axis cylinder at every injured spot.
Both neutral red and toluidine blue are readily precipitable by
_KCl, and the granules stained by these dyes are probably caused
by the diffusion of this electrolyte.

(8) The theory deduced from these observations is that the axis
cylinder is surrounded by an impervious wall except at Ranvier’s
nodes, and is filled with a colloidal solution with potassium chlorides
adsorbed on the surface of the colloid molecules. As the salt is
attached in this manner it is supposed to be masked, so that it
does not give the potassium reaction, and does not exert osmotic
pressure, but can still conduct electricity. Injury (and to a less
extent excitation) causes these colloid molecules to aggregate and
become larger (*). Their surface is therefore diminished, and the
electrolytes are set free into simple aqueous solution. From the
nature of the precipitates by Macallum’s methods the electrolyte
is inferred to be KCl, and the neutral red and toluidine blue
precipitates confirm this. The concentration of salt is from the
“concentration law” about 10 per cent. This theory is therefore
a purely physical one, and has a close relationship to the theory
propounded by Sutherland (*). Both these theories give an
intelligible explanation of what has always been a difficulty,
namely, the peculiar rate of transmission of the nervous
impulse (& ®),1

While this Macdonsld-Sutherland hypothesis would explain
the observations just referred to, there are still many difficul-
ties to be faced, some of which are of a formidable character.
Potassium chloride is supposed to be masked in such a manner
that it exerts no osmotic pressure, yet that the ions can move so
as to conduct electricity. It is supposed to be present as KCl,
yet Cl appears at once on the use of AgNO,, while the K is masked
and only appears when there is an injury—a return by a back door
to the “alteration-theory”” that had been abandoned. The rate
of diffusion of the +K ion is -00066, of the —Cl ion is -00069,

1 The most recent determinations (**) give the rate at 30 metres per second in the
frog’s nerves at ordinary temperatures, 65 metres per second at 35° C. Helmholtz
gave 33 metres per second for human nerve (which would make this process in
man at 36° occur at the same rate as in the frog at 15° C.) But as Tigerstedt
points out, the arm of this subject was cooled by a casing of plaster of Paris, and

so this’ value is too low. Waller gives 50 metres per second ; Alcock as the mean
of forty experiments on man gave 66 metres per second.

so that to produce a current in the right direction diffusion must
be supposed to be faster down the nerve than into the electrodes.
Finally, as the difference in velocity of the two ions is so small,
and as the E.M.F. is the difference of the diffusion into electrodes
and nerve, a very high concentration is needed—according to the
‘concentration law” equal to 10 per cent. KCl—yet the chemical
analysis of the tissue (as far as the observations go) shows that
even if all the K and Cl be supposed to be present in the axis
cylinder and none elsewhere, there is not enough to give a con-
centration of more than ‘5 per cent. at the outside.

IIT. The theories based on fluid cells are at first sight more
promising, especially as it has not yet been possible to give exact
details which can be put to the test of direct experiment.

The view of Brunings (*), perhaps the best instance of this
theory, is that animal electricity in general, and nerve in par-
ticular, is an example of a “diosmotic cell.” This is an arrange-
ment by which two fluids, which may be of the same osmotic
pressure but differ in composition, are separated by a membrane,
which is impermeable to both fluids as a whole, but permeable
to at least the kation of the fluid lying within the cell. Such an
arrangement would give a current on fracture of the membrane,
would not give heat externally, would show the same osmotic
phenomenon as a nerve, and does not require a greater concen-
tration of electrolytes than is met with elsewhere in the body.!
The electrolytes are supposed to be “ preformed” ; they might be
adsorbed on the surface of protein molecules or not.

Alcock (**) has published some results on the electrical con-
ductivity of nerve before and after chloroform and ether anesthesia
which bear on the question, if the assumption is made that these
agents produce a maximum injury. As both drugs cause an
electrical effect of the same sign as the injury current and of the
same order of magnitude this is not an unreasonable hypothesis.
The result is that in nerve there is no alteration of conductivity
(within 2 per cent.), while there is a marked diminution in the
polarisation.? The inference from this is that chloroform does

280 _ SOME CHAPTERS ON THE

1 Alcock and Lynch (®) give the figures for chlorine in nerve fibres. Some
unpublished results on the. potassium content support the view given above, but

_ the experiments are still too\few in number to justify the pronouncement of a final

opinion.
* Waller (°’) had previously observed the alteration in polarisation. His‘ results P
do not contradict those of Alcock, as Roaf and Alderson (**) suppose.

PHYSIOLOGY OF NERVE 281

not in nerve set free electrolytes! and if the preliminary
- assumption be granted, that there are none set free by an injury.
This is quite consonant with the theory just stated, but presents
some difficulty to the concentration cell theory. Macdonald’s
invocation of “ pseudo polarisation,” and his supposition that the
electrolytes in nerve are free to conduct electricity but not to
exert osmotic pressure, is an explanation that seems to require
a further experimental basis before it can be unreservedly
accepted.

It might be supposed that the location and properties of the
membrane or surface of separation which divides the fluids would
_ present some difficulties. Ostwald (7°) originally showed that such
a membrane could exist, and that it might be permeable to either
kations or anions, but not to both. .In the case of nerve the
membrane would have to be permeable to kations alone, as stated
above. Alcock’s (*) further observations on the action of chloro-
form showed that while the results on nerve could be taken either
way, the experiments on frog’s skin required for their explanation
the presence of such membranes situated just below the outer
surface, and that no simple diffusion process would be sufficient.
So that as far as the membrane is concerned both the “‘ concentra-
tion cell” and the “diosmotic”’ theories have some experimental
justification.

Here the subject must be left as far as the present occasion is
concerned. For the future we may hope that further experiment
will enable us to decide between the present series of conflicting .
hypotheses.

Although we have considered the matter solely from the stand-
point of nerve, it is admitted that the same laws govern the life
of every cell in the body, and the inquiry is really a fundamental
one into the properties of living matter. To any one who takes
an interest in anything beyond the routine work of examinations
such inquiries cannot fail to be of the greatest importance, and it
is only in physiology that it is necessary to defend the acquisition
of knowledge for its own sake.

* Moore and Roaf (**) and Roaf and Alderson (**) have advocated the contrary

view as far as the action of CHCl, is concerned, but the discussion is too elaborate
to be continued in this place.

2 SOME CHAPTERS ON THE

BIBLIOGRAPHY

1 J. C. Bose, Comparative Electrophysiology, London, 1907.

2 A. D. Waller, Proc. Physiol. Soc., J. Physiol., 37, xviii.

3 J, C. Bose, Response in the Living and Non-Living, London, 1902.

* F. Gotch, J. Physiol., 28, p. 32.

5 H. von Baeyer, Verworn’s Zeitschrift, Bd. 2, H. 1, p. 169.

° F. W. Fréhlich, Verworn’s Zeitschrift, Bd. 3, H. 1, p. 75.

? K. H. Baas, Pfluger’s Archiv., Bd. 103, p. 276.

8 A. D. Waller, Lectures on Animal Electricity, vol. i.

® F. Gotch and v. Horsley, Phil. Trans. Roy. Soc., 182, 1891, p. 514.

10 (, S. Sherrington, Integrative Action of the Central Nervous System,

New York, 1906.

1 Bernstein, Pfluger’s Archiv., Bd. 73, s. 376, 1898.
2 N. H. Alcock and J. Seemann, Pfluger’s Archiv., Bd. 108, s. 426.
8 W. Reid and J. S. Macdonald, J. Physiol., 23, p. 100.

14 M. Lewandousky, Pfliiger’s Archiv., Bd. 73, p. 288; and Inaug. Dissert.
Halle a. S., 1898.

%° W. Einthoven, Pfliiger’s Archiv., Bd. 124, s. 246.

6 F. Gotch and G. J. Burch, J. Physiol., 24, p. 410, 1889.

™ Bernstein, Pfluger’s Archiv., Bd. 15, p. 289.

8 Wedenski, Medisch. Zentralbl., 1884, p. 64.

® Bowditch, Du Bois Reymond’s Archiv., 1890, p. 489.

0 Brodie and Halliburton, J. Physiol., 28, p. 181, 1892.

1 S.C. M. Sowton, Proc. Roy. Soc., vol. 66, p. 379.

2 §. Garten, Beitrage zur Physiol. der Marklosen Nerven, Jena, 1903.

*3 V. H. Alcock, Proc. Roy. Soc., 1904, vol. 73, p. 166; 1906, vol. 77, p.

267; 1906, vol. 78, p. 159.

4 J. Tait and Gunn, Quart. Journ. Exper. Physiol., i. p. 1.

*% A.D. Waller, Proc. Physiol. Soc., J. Physiol., 25, p. i., and 36, p. xxx.
*° A. D. Waller, Proc. Physiol. Soc., J. Physiol., 36, xxx.

7 KH. Pfluger, Pfluger’s Archiv., Bd. 122, p. 593.

*8 B, Kilvington, British Medical Journal, 1905, i. p. 935 ; 1905, ii. p. 625;

1907, i. p. 988; 1908, i. p. 1414.

*® W. Thorner, Verworn’s Zeitschrift, Bd. 8, H. 5, p. 530.

82 Kilvington and Osborne, J. Physiol., 34, p. 267.

33 Marinesco, J. f. Psychiat. u. Neurologie, vii. p. 141.

%4 Halliburton, Mott, and Edmunds, Proc. Roy. Soc., B. 78, p. 259, 1906.

35 Langley and Anderson, J. Physiol., 30, p. 439.

3 Lugaro, Neurol. Zentralblatt, 25, p. 786.

°° Harrison, Ross, Archiv. f. Mikros. Anat. u. Entw., 57, 1901.

40 Harrison, Ross, Sitzungs b. d. N. Gesell. f. Nat. u. Heilk., 1904.

“ Ballance and Stewart, The Healing of Nerves, 1902.

“8 R. Kennedy, Phil. Trans., B. 188, 1897, p. 257; Brit. Med. Journ., 1904,
\

ii, p. 729.

“4 Head, Rivers, and Sherren, Brain, 28, p. 99, 1905.
“* Head and Sherren, Brain, 28, p. 116, 1905.

PHYSIOLOGY OF NERVE 283

© Head and Thompson, Brain, 29, p. 537, 1906.

“ Bethe, Alig. Anat. u. Physiol. der Nervensystems, 1903.

“ Braus, Anat. Anzeiger, 26, p. 433, 1905.

® Kerr, Graham, Roy. Soc. Edin. Trans., vol. 41, 1905, p. 121.

® Ballance and Stewart, Brit. Med. Journ., 1903, May 2.

5 A, Macallum, J. Physiol., 32, p. 95.

- © Gilbert, Inaug. Dissert., Tubingen, 1898.

53 Macallum and Menten, Proc. Roy. Soc., B. 77, p. 165, 1906.

54 4. Macallum, Proc. Roy. Soc., 76, p. 217.

% Mazwell, J. Biol. Chemistry, iii. 1907, p. 358.

5° Keith Lucas, J. Physiol., vol. 37, 1908, p. 112.

5? Bazett, J. Physiol., 36, p. 414, 1908.

88 Woolley, J. Physiol., 37, p. 122, 1908.

59 J, S. Macdonald, Proc, Roy. Soc., 67, p. 315, 1900, and p. 325, Lc.
Thompson-Yates Lab. Reports, 4, p. 2, 1902. J. 8. Macdonald and 8. C. M.
Sowton, ibid., Feb. 5, 1903. J. S. Macdonald, Proc. Physiol. Soc., J. Physiol.,
Dec. 17, 1904 ; March 18, 1905. Proc. Roy. Soc., 76 B., p. 322. Proc. Physiol.
Soc., J. Physiol., June 17, 1905. Proc. Roy. Soc., 79, p. 12, 1906.

© N. H. Alcock and G. Roche Lynch, J. Physiol., 36, p. 93.

%1 J. H. Ashworth, Proc. Roy. Soc., B., vol. 80, p. 463.

82 J. S. Macdonald, Science Progress, vol. 2, p. 482.

6’ W. Sutherland, Am. Journal Physiol., 1906, vol. 17, pp. 266, 297.
*« N. H. Alcock, Proc. Roy. Soc., 1903, vol. 72, p. 414.

* yon Miram, Engelmann’s Archiv., 1906, p. 533.

%® W. Brunings, Pfluger’s Archiv., Bd. 100, p. 367.

* A, D, Waller, Proc. Physiol. Soc., J. Physiol., 38, p. vi.

% B, Moore and H. E. Roaf, Proc. Roy. Soc., vol. 73, 1904, p. 382; B.,
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® H, E. Roaf and E. Alderson, Biochem. Journal, vol. ii. p. 412.

()stwald, Zeitsch. f. Physik. Chemie, vol. 6, 1890.

7

RECENT RESEARCHES ON CORTICAL LOCALI-
SATION AND ON THE FUNCTIONS OF THE
CEREBRUM

By JOSEPH SHAW BOLTON

INTRODUCTION

THE experimental study of the functions of the cerebrum, after a
period of activity lasting through three decades, reached its acme
in an important research (Sherrington and Griinbaum), which
resulted in the belated recognition of the histological investigation
of Bevan Lewis and Henry Clarke (1878) on the cortical localisa-
tion of the motor area of the brain. Of late years the histological
has largely replaced the experimental method, and the study of
cortical localisation, although still in its infancy, may now fairly
claim to be regarded as a branch ot exact science.
Owing to the far-reaching importance of the controversy regard-
ing the neurone theory, the majority of the numerous recent
publications on the anatomy and histology of the nervous system
deal with the finer histology of nerve cells and fibres. Of 711
contributions, for example, which appeared during the years 1905
and 1906, and which were critically abstracted and reviewed by
Edinger and Wallenberg in their last report, over 300 papers
were concerned with this subject, and few of the remainder were
of direct physiological significance. It is not the purpose of this
article to deal with purely histological investigations which have
no immediate bearing on cortical localisation, and therefore no
reference will be made to such contributions beyond the remark
that, of those by English writers, the papers of John Turner are .
especially worthy of attention. 7.
During the past eight years numerous publications have
appeared on the subject of cortical localisation by the histological
- method. In these several contributions the mode of evolution —
and the functional significance of the different cell layers of the i
cortex cerebri have been Scneiaanet from both the ontogenetic ‘

2

RECENT RESEARCHES 285

and the phylogenetic aspects; and the whole cortex cerebri in

many orders of mammals (including man) has been mapped out
into various histologically different regions.

Of these regions, experimental or histo-pathological proof of
the functions of the precisely-defined psychomotor and visuo-
sensory areas is complete. In the case of the prefrontal region,
which is the latest evolved, the most variable, and the most com-
plexly constructed portion of the human cerebreum, histo-patho-
logical evidence of its functional significance has’ been derived from
the examination of cases of mental disease, which method consti-
tutes an advance on the time-honoured study of cases of gross
lesion of the brain.

. Finally, with regard to the localisation of the language centres,
important papers by Marie and by Monakow, and a lengthy volume
by Moutier, have been published; and the existence of Broca’s

: speech area has thereby been seriously threatened if not ren-

| dered entirely doubtful. Articles on the psychological experiences

| connected with the different parts of speech, on the language

| mechanism and its psycho-physiology with regard to the functions
of the cerebrum, and on the subject of sense-deprivation, have also
been recently published.

In the course of the present article, the lamination of the cortex
cerebri and the functional significance of its several layers will
first be considered. The subject of cortical localisation by means
of the histological method will then be detailed. This description
will be followed by remarks on the mode of evolution of the
cerebral functions. The higher functions of the human brain will’
afterwards be dealt with, and in connection with this matter the
psycho-physiology of the language mechanism will be discussed.
The subject of sense-deprivation will next receive attention, as

_ @ preliminary to the consideration of the recent researches on
aphasia. The article will be concluded by references to certain
matters of interest with regard to the functions of the cerebrum,
and to a number of recent publications of importance, which
could not be conveniently included in the general text.

LAMINATION OF THE CorTEX CEREBRI

i? Since the year 1872, when Meynert published a description of
___ the structure of the cortex cerebri which, from the general aspect,

286 RESEARCHES ON CORTICAL LOCALISATION AND {™

has required little modification, numerous classifications of the
various layers of which it is composed have appeared.

The various subdivisions which have been made by the several
authors, owing to the different methods of preparation which have
been employed, to the different aspects from which the subject
has been studied, and to the different regions of the cortex cerebri
which have been examined, have resulted in the employment
of different numerals to designate the same or similar layers ;
and thereby much confusion has resulted. This will be avoided
during the following description by the employment of such
terms as clearly indicate the cell layers which are under
reference.

Whilst from the aspect of cell form, few if any of the published
descriptions equal in elaboration, and in probable accuracy, the —
account given by Cajal in the numerous papers he has produced
as the result of a systematic employment of various modifications

_ of the method of Golgi, his classification is at present of histo-

logical rather than of physiological interest.

Another and more recent classification, that of Brodmann (1906),
is more immediately useful, and, in consequence of the elaborate
and prolonged investigations of the author on the subject of
cortical localisation, deserves reference here. Brodmann divides
the cortex cerebri into the following layers :—

(1) A zonal layer, without cells (the equivalent of the tangential
layer of Krause)..

(2) A layer composed of the “ molecular” and “small pyra-
midal ” layers of other writers.

(3) A layer of medium and large pyramidal cells.

(4) An internal granular or stellate layer.

(5) A layer of ganglionic or deep pyramidal cells.

(6) A layer of deep spindle-shaped or polymorphous cells.

For the purposes, however, of this article, which deals with
the subject from the functional rather than the structural aspect,
the description has been adopted which was published by the
present writer in 1900, and which is based on the mode of develop-
ment of the several lamine of the cortex cerebri. This classifica-
tion, which has been adopted, amongst others, by Mott and by
Watson, is as follows :—

(1) The superficial layer of nerve fibres or “ molecular” layer
(outer fibre lamina). (Average prefrontal depth, -30054 mm.)

ON THE FUNCTIONS OF THE CEREBRUM — 287

(2) The layer of small, medium, and large pyramidal cells
(outer cell lamina). (Average prefrontal depth, ‘83116 mm.)

(3) The layer of granules (middle cell lamina). (Average pre-
frontal depth, :22883 mm.)

(4) The inner layer of nerve fibres or “ inner line of Baillarger,”
containing large and frequently solitary cells (inner fibre lamina).
(Average prefrontal depth, ‘23032 mm.)

(5) The layer of polymorphic cells (imner cell lamina).
(Average prefrontal depth, -30979 mm.)

This five-layered type, though subject in different regions to
structural modifications which probably possess in all cases a
functional significance, is common to the whole cortex cerebri,
with the exception of the hippocampus and the pyriform lobe,
which parts belong to the archipallic, in contradistinction to neo-
pallic cortex (Elliott Smith). In the psychomotor area, for example,
the Betz cells lie in the inner fibre lamina, and the middle cell
lamina is reduced in depth almost to vanishing point. Again, in .
the visuo-sensory area, the middle cell lamina is hypertrophied
and duplicated by the interposition of a special fibre layer, the
line of Gennari.”

The mode of development of this five-layered type of cortex will
now be briefly described.

In the foetus of four months lamination has not begun, and the
cortex consists solely of a superficial indifferent layer and of a
deeper layer of undifferentiated neuroblasts. The average depth
of the former is 0°154665 mm., and of the latter 0°67758 mm., a
total of 0°832245 mm., which is less than half the normal adult >
general average depth of 1-90064 mm. |

For simplicity of exposition, the process of development will
be first deseribed in the case of each separate layer, and the results
- will then be summarised.

Prmary Cet, LAMIN® OF THE Cortex

Lamina 2, Pyramidal Layer, Outer Cell Layer—The pyramidal
layer is the last cell layer of the cortex to develop during the
process of lamination. In a foetus of six months this layer is
separable from the subjacent middle cell layer owing to the less
differentiated condition of its cell elements, and it is at this period
only one-fourth of the depth to which it attains in the adult. At

ie Se o ’ ea

288 RESEARCHES ON CORTICAL LOCALISATION AND .

birth and in early infancy it is still little more than one-half of the
adult depth.

Lamina 3, Granule Layer, Middle Cell Layer.—The granule layer
develops in the sixth month of foetal life, and at this period it is
separable from the superjacent outer cell or pyramidal layer owing ~
to the more differentiated condition of its cell elements. At this
period it is already one-half of the adult depth, and by the time
of birth it has attained to a depth which is nearly three-fourths
of this.

Lamina 5, Polymorphic Layer, Inner Cell Layer—The poly-
morphic layer is the first cell layer to appear, and it is separated
off from the rest of the partially differentiated neuroblasts of the
cortex by the development of the fourth or inner fibre lamina at
the sixth month of foetal life. The polymorphic layer is already, —
at the period referred to, about three-fourths of the adult depth,
and it undergoes a slow further development until after birth. In
a child of six weeks it has attained a depth which is within 18 per
cent. of the adult normal.

PRIMARY FisRE LAMINA OF THE CorRTEX

Lamina 1, Superficial Layer, Outer Fibre Layer —At the fourth
month of foetal life the cortex consists of this layer and of a
deeper undifferentiated mass of neuroblasts. The layer under
description is already about one-half of the adult depth, and it
remains unchanged until the development of lamination in the
sixth month. At birth, however, it has attained to a depth which
is about two-thirds of the adult normal. It is probable that its
further development to the normal adult depth occurs in associa-
tion with that of the subjacent second, pyramidal, or outer cell
layer. :

ees 4, Inner Fibre Layer, Inner Line of Baillarger—This
layer appears in the sixth month of foetal life, and almost at once
attains to nearly the normal adult depth. The cleavage of the Vi
partially differentiated neuroblasts of the cortex into an upper and =
a lower portion by the development of this layer is the most striking i
feature of the process of lamination. In view of what will be 4
stated later concerning the functions carried on by the inner cell
layer, this cleavage of the neuroblasts is an occurrence of the

greatest significance.

ON THE FUNCTIONS OF THE CEREBRUM 289

Summary.—The inner cell layer, therefore, appears before the
others, in consequence of a cleavage of the undifferentiated neuro-
blasts into an upper and a lower portion, and it is almost at once
of a depth which is about 75 per cent. of the adult normal. It
remains at almost a stationary depth until after birth. Its depth
in a child of six weeks is 82 per cent. of the adult normal.

The middle cell layer is differentiated next in order, and is
almost at once about one-half of the normal adult depth. It
gradually increases in thickness, and at birth it has attained to a
depth which is 75 per cent. of the adult normal.

The outer cell layer is the last layer of the cortex to be
differentiated, and at this time it is only one-fourth of the normal
adult depth. It gradually increases in thickness, and in an infant
of six weeks it has attained to a depth which is about 60 per cent.
of the adult normal.

In the adult human cerebrum, as will at once be seen from
the measurements given on page 287, the outer cell lamina or
pyramidal layer, in spite of its late evolution, becomes the promi-
nent layer of the cortex, and in depth is greater than the depth
of the combined layers 3, 4, and 5, which lie below it. The
functional significance of the facts mentioned in this description
will be referred to later.

SS

The above account of the mode of evolution of the cortex cerebri
has recently been confirmed by G. A. Watson from the phylogenetic
aspect. This writer, whilst hitherto paying especial attention to the
insectivora, has carefully studied the cortex cerebri of many orders
of mammals. He adopts the above classification of the cortical layers,
but, for reasons which he details, employs a slightly different termi-
nology, grouping the first and second lamine together under the term
** supra-granular,” and the fourth and fifth together under the term

_ *infra-granular.” He remarks :—

“ Regarded from the developmental aspect—ontogenetic and phylo-
genetic—the facts adduced support the thesis that the mammalian
cerebral cortex (neopallium) is built up primarily on an infra-grandlar
basis, 7.e. the infra-granular portion is the earliest to appear in the
process of development, very quickly reaches maturity, and in the
adult, especially if average size of component nerve cell is taken into

consideration, presents remarkably little difference in absolute depth
in one of the lowest mammals and in the highest.
“The granular layer may be said to be the next addition to the

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290 RESEARCHES ON CORTICAL LOCALISATION AND

cortex. Ontogenetically it appears shortly after the infra-granular
portion of the cortex, and it reaches its maximum development in
depth and definiteness in the projection spheres of the cerebrum. The
last layer of the cortex to appear ontogenetically is the supra-granular
(pyramidal). It is the slowest of all the layers to reach maturity.
It is scarcely existent at all in certain regions in some of, if not all,
the lowest mammals, and even at its best in the latter it reaches
but a slight absolute depth as compared with its depth in practically
every region of the neopallium in the human subject.”

The above description of the mode of development of the cortex
cerebri is illustrated in the following figure, which indicates, in
graphic form, the five primary cell and fibre laminz of the cortex
of foetuses of four and six months, a new-born child, a normal
human adult, and a mole. It will be at once seen that the cortex
of the human adult differs from that of the insectivore chiefly in
the degree of development of the second, pyramidal, or outer cell -
lamina. In spite of the human brain being one of the largest and
that of the mole one of the smallest in the mammalian phylum, the
actual average depths of the granular and infra-granular portions
of the cortex (laminz 3, 4, and 5) are very similar in the two.

It may here be remarked that Brodmann, in the course of his
prolonged investigations into the structure of the cerebral cortex of
the mammalia, has incidentally and independently (1906) made similar
observations to those of Watson. He states that, during the ascent
of the mammalian series, his layer 3, which is substantially the outer
cell lamina or pyramidal layer of the writer and the supra-granular
layer of Watson, increases in depth, whilst his layer 6, which is
equivalent to the inner cell lamina 5 of the writer and the lower
part of the infra-granular region of Watson, on the whole diminishes
in depth. Brodmann also makes certain generalisations regarding
the variability of the individual layers of the cortex cerebri, which,
though they confirm the individual observations of several other
writers, are worthy of reference here owing to the wide field covered
by the investigations of this author. He remarks that his layer 4
(granule layer of other writers) is the most variable; that his layers 3
and 5 (medium and large pyramids, and infra-granular pyramidal-
shaped cells) exhibit the greatest histological differentiation ; and that
his layer 6 (polymorphic layer or inner cell lamina of the writer)
exhibits the greatest variation in breadth. He further remarks that
the psychomotor and striate (visuo-sensory) areas of the cortex cerebri
are most highly developed in primates,

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lamin of the cortex cereb

The Visuo-sensory Area.—The lamination in this

primary

f the human cortex cerebri, will now be briefly detailed,

ON THE FUNCTIONS OF THE CEREBRUM 291
Certain facts regarding the lamination, the period and the mode

of its evolution, and the functional significance of certain special

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292 RESEARCHES ON CORTICAL LOCALISATION AND —

specialised from the five-layered type already referred to, and -
consists of the following layers :—

1. The superficial layer of nerve fibres (outer fibre lamina).

2. The layer of pyramidal cells (outer cell lamina).

3a. The outer layer of granules.

3b. The middle layer of nerve fibres or “line of | (middle cell
Gennari ” containing solitary cells of Meynert. lamina).

3c. The inner layer of granules.

4. The inner layer of nerve fibres or “ inner line of Baillarger,”
containing solitary cells of Meynert (nner fibre lamina).

5. The layer of polymorphic cells (inner cell lamina).

The specialisation of the visuo-sensory cortex consists, there-
fore, in essentials, in a duplication of the third primary lamina of
the cortex, and in the interposition, between the double layer, of .
a layer composed of nerve fibres. Of this triple layer, layer 3a is
an additional feature; layer 3b is an exaggeration of a thin fibre
band, the “outer line of Baillarger,’ which in the adult cortex
lies between the second and third primary lamine, but is only
visible in sections prepared to show nerve fibres; and layer 3c is
the original third primary lamina increased in depth.

In congenital or long-standing blindness the depth of. layer 3b
is decreased by nearly 50 per cent., and that of layer 3a is
decreased by more than 10 per cent., owing to atrophy of the
optic radiations. The other layers of the cortex are unchanged
in depth by the existence of blindness.

These facts prove that the cortical region under consideration
is the projection centre for visual impressions or the visuo-
sensory area.

The cortex in this region rapidly attains to mature develop-
ment. The second, pyramidal, or outer cell lamina thus develops
much earlier than is the case in the visuo-psychic and prefrontal
regions. For example, in infants of one and three months re-
spectively, its depth is already 84 per cent. of the adult normal.
A further important fact is that in the normal adult this cell layer
of the visuo-sensory area\is only about five-ninths of its depth in
the visuo-psychic and prefrontal regions of the cerebral cortex.

The Visuo-psychic Region.—At the periphery of the visuo-sensory
area, where this passes in each direction into the neighbouring
cortex, termed by the writer “ visuo-psychic” (which word has
since been adopted by Campbell and by Mott), an abrupt change

ON THE FUNCTIONS OF THE CEREBRUM 293

in lamination takes place, layer 3b, the line of Gennari, suddenly
ceasing, and layers 3a and 3c, the two layers of granules, running
into one and becoming layer 3 of the visuo-psychic region, which

is thus of the ordinary five-layered type.

Congenital or long-standing blindness causes no modification of
the lamination of the visuo-psychic region, which fact proves that
this region possesses no “ visuo-sensory ” functions.

The cortex of this region reaches maturity later than the visuo-
sensory, but earlier than the prefrontal. The second, pyramidal,
or outer cell Jayer in infants of one and three months is respec-
tively nearly two-thirds and more than three-quarters of the
normal adult depth. This layer reaches to practically the same
adult depth as in the prefrontal region. In cases of mental disease
this layer does not vary in depth according to the degree of
dementia existing in the patients, though a small and practically
constant decrease in depth, which may be due either to sub-
development or to retrogression, is evident in such cases.

The Prefrontal Region.—The cortex of this region is late in
reaching maturity. As hes been stated, the pyramidal or outer
cell lamina is the last layer of the cortex to develop. Jt is visible
owing to the undifferentiated condition of its constituent neuro-
blasts in a foetus of six months, and is at this time only one-
quarter of the normal adult.depth. In infants at birth and at
the age of six weeks it is still less than two-thirds of the normal
adult depth.

It is the only cell layer of the cortex cerebri which varies -
measurably in depth in “ normal” brains.

In cases of mental disease it is under- -developed to different
degrees, not only in idiots and imbeciles, in the severer grades of
which its depth is only two-thirds of the adult normal, but also,
and here to a lesser extent, in chronic and recurrent lunatics
without dementia. The degree of its retrogression in demented
patients varies directly, and to an equally marked degree as its
subdevelopment in the case of amentia, with the amount of
dementia existing in the respective cases.

Of these three” regions of the cortex, therefore, the visuo-
sensory area first reaches maturity. Though highly specialised,
the cortex of this area is, however, not well developed, as the

outer cell lamina or pyramidal layer remains at but five-ninths of

* - F |

294 RESEARCHES ON CORTICAL LOCALISATION AND

the maximum adult depth. The visuo-psychic cortex attains to
maturity later, but then becomes of the maximum adult depth.

The prefrontal cortex is the last to reach maturity. The outer |
cell lamina in this region varies in its degree of development
according to the mental capacity of the individual and in its degree

of retrogression according to the amount of mental decadence
which exists. Further, it varies in measurable depth in “ normal ”
individuals.

All these variations regarding the degree of development occur
in the pyramidal or outer cell layer, which is the last lamina to
be evolved, and the most important feature of the human adult
cortex cerebri.

The inner cell lamina or polymorphic layer of the cortex, which
is the first to be evolved, is, on the other hand, in all the three ©
regions referred to above, of extremely constant average depth.
A very slight decrease in the average depth of this layer occurs,
in the prefrontal region, in cases of mild cerebral and mental
degeneracy (high-grade amentia), and in cases of chronic insanity
with moderate dementia. A considerable decrease, on the other
hand, exists, also in the prefrontal region, in more marked aments
(whether normal foetuses and infants, or idiots and imbeciles) and
in gross dements who are unable to carry on the ordinary animal
functions, such as attending to their own wants, &c.

FUNCTIONS OF THE DIFFERENT CELL LAMINZ OF
THE CORTEX CEREBRI

As has been stated, the cerebral cortex consists of three primary
cell lamine (layers 2, 3, and 5), and of two primary fibre lamine
(layers 1 and 4). The evidence above adduced regarding the
ontogenetic and phylogenetic development of these lamin enables _
certain definite conclusions to be drawn with regard to their
functional significance.

The outer cell lamina (2, pyramidal), to which may be added
the outer fibre lamina (1), is the prominent feature of the human
cortex, and constitutes a “higher level” basis for the carrying
on of the cerebral functions. It is the last cell layer of the cortex
to be evolved and the first to undergo retrogression. In the
visuo-sensory area (projection sphere) the outer cell lamina rapidly
attains maturity, but is then only about five-ninths of its depth

ON THE FUNCTIONS OF THE CEREBRUM = 295

in the visuo-psychic and prefrontal regions of the cerebral cortex.
In the visuo-psychic region this layer develops earlier than in the
prefrontal region, but later than in the visuo-sensory area, and
eventually attains to practically the same adult depth as in the
former. In this region it is of practically constant adult depth,
and does not vary in measurable depth according to the mental
capacity of the individual. In the prefrontal region the outer
cell lamina develops later than in the other regions referred to
It is the only cell layer of the cortex cerebri which varies definitely
in measurable depth in “normal” brains. It is under-developed to
different degrees according to the mental capacity of the individual
| in persons exhibiting various grades of mental subevolution ; and
| it undergoes degrees of retrogression which correspond to the
amount of dementia existing in cases which permanently suffer
from diminution or loss of their mental powers.

The second, pyramidal, or outer cell lamina of the human cerebral
cortex, therefore, subserves the “‘ psychic” or associational functions
of the cerebrum. These functions are pre-eminent in the prefrontal
region (centre of higher association); they are less important in
the visuo-psychic region (region of lower association) ; and they are
of least importance in the visuo-sensory region (projection sphere).
These three regions are therefore of different grades in the hierarchy
of cerebral function.

The results obtained by Watson during his histological investiga-
tion of the cerebral cortex of the mammalia supply the complement
from the phylogenetic aspect to the above (ontogenetic) conclusions. .
Watson finds that in the insectivora the pyramidal or outer cell layer
is in a rudimentary condition, though the lower layers of the cortex
approximate in depth to that of these layers.in the normal human
adult. Further, the pyramidal or outer cell layer is better developed
. in the rodents than in the insectivores; it is again better developed
in the ungulates and in the carnivores than in the rodents; and it
is strikingly more developed in the primates than in the carnivores.
He therefore functionally correlates this layer with the educa-
bility and general intelligence which appear in an increasing degree
during the ascent of the mammalian scale.
Watson remarks :—
“The supra-granular (pyramidal) layer—which is, relatively to
the infra-granular cortex, so poorly developed at birth—is slow in
reaching maturity, and is, even at its best, in certain lower mammals,

296 RESEARCHES ON CORTICAL LOCALISATION AND

such as the insectivora, only of an insignificant absolute depth—
subserves the higher associations, the capacity for which is shown by
the educability of the animal. It has therefore to do with all those
activities which it is obvious that the animal has acquired (or per-
fected) by individual experience, and with all the possible modifica-
tions of behaviour which may arise in relation to some novel situation,
hence with what is usually described as indicating intelligent as apart
from instinctive acts, the former being not merely accompanied but
controlled by consciousness (Lloyd Morgan).”

The middle cell lamina (3, granule) is developed after the fifth,
polymorphic, or inner cell lamina, and before the second, pyramidal,
or outer cell lamina. In the prefrontal region of a foetus of six
months it has just become differentiated, by commencing specialisa-
tion of its constituent cells, from the superjacent second or outer -
cell lamina, and it is already one-half of the normal adult depth.
In a child at birth it has become three-fourths of the normal adult
depth. .

In the visuo-sensory area the optic radiations end in the midst
of a hypertrophied and duplicated third or granule layer. The
duplication is due to the interposition in the midst of the hyper-
trophied third or granule layer of a well-marked fibre band, the
line of Gennari, which fibre band, as has already been stated, is
a hypertrophy of the outer of the two horizontal interradiary fibre
plexuses of the adult cortex, namely, the “ outer line of Baillarger.” .
In old-standing or congenital optic atrophy, the outer (and addi-
tional) of the granule layers is decreased in thickness by more than
10 per cent., and the line of Gennari is decreased in thickness by
nearly 50 per cent. .

As has been pointed out by Watson, a hypertrophied third,
granule, or middle cell lamina appears to be characteristic of the
projection areas of the cerebrum. In the case of the visuo-
sensory area (visual projection sphere), the third or granule layer
first becomes definitely duplicated in the order primates, though
slight indications of duplication occur in the higher carnivores.

The third, granule, or middle cell lamina, therefore, primarily
subserves the reception or immediate transformation of afferent im-
pressions, whether these arrive directly from the lower sensory neurones —
- or indirectly through other regions of the cerebrum. .

‘The fifth, polymorphic, or inner cell lamina is the first cell lamina
of the cortex cerebri to be differentiated during the process of

ON THE FUNCTIONS OF THE CEREBRUM ~ 297

lamination. In the prefrontal region of a foetus of six months it
is separated off from the rest of the cortex by the fourth or inner
fibre lamina, and is already within 29 per cent. of the normal
adult depth. In a child of six weeks it has advanced to within
18 per cent. of the normal adult depth.

It is of extremely constant average adult depth.

A very slight decrease in the depth of this layer exists in cases
of high-grade amentia and of chronic insanity with moderate
dementia. A considerable decrease, on the other hand, exists in
more marked aments (whether foetuses and infants, or idiots
and imbeciles), and in gross dements who are unable to carry on
_ the ordinary animal functions, such as attending to their own
wants, &c.

The fifth, polymorphic, or inner cell lamina of the human cerebrum,
therefore, in association with the fourth or inner fibre layer, subserves
the lower voluntary and instinctive activities of the animal economy,
and thus forms a lower level basis for the carrying on of cerebral
function.

Final proof of the last statement has, from the phylogenetic
aspect, been afforded by the researches of Watson, who has shown
that the “ infra-granular ” region contains the important cell layers
of the lower mammalia, and is very little inferior in depth (see
Fig. 1, page 291) to the normal adult human depth of the conjoined
fourth and fifth lamine. )

Watson’s conclusions on this question are as follows :—

“The infra-granular portion of the cortex (iv. and v.) (omitting
the constituent cells which possess motor or analogous functions) is
concerned especially with the associations necessary for the perform-
ance of the instinctive activities, that i is, all those which are innate
and require for their fulfilment no experience or education. These
form the basis of many complex actions necessary for the preservation
of the individual and the species, such as the seeking appropriate
shelter and protection, the hunting for food—each after his own kind
—and the quest of the opposite sex. Although these acts may be
accompanied by consciousness, there is no evidence to show that this
is ‘focal’ or that essentially they are controlled by consciousness
(Lloyd Morgan). It is believed that lower mammals have provided in
the infra-granular cortex (which is relatively so fully matured at birth
in them as well as in man, and which in the adult, even in animals

aS gd down in the mammalian scale, reaches such a great degree of

298 RESEARCHES ON CORTICAL LOCALISATION AND —

absolute development) a sufficient cerebral cortical mechanism for the
performance of these lower associations. The actions which are the
outcome of such associations are often complex, and as an instance
of the class included under this heading the tunnelling of the mole
may be mentioned. Such more or less stereotyped actions may show
signs of improvement in their performance, firstly, as the result of
perfection by use of an inherited mechanism, and secondly, as the
result of the intermingling of activities for which it is concluded that
the supra-granular layer is responsible. In the latter case, however,
the actions would merge into those which are more properly described
as habitual intelligent, or into the class of ‘incomplete instincts’
(Lloyd Morgan), or ‘ mixed instincts ’ (Romanes).”

Watson finally remarks, on the subject of the functions of the
“‘ supra-granular”’ (outer cell layer) and “ infra-granular” (inner
fibre layer and inner cell layer) :—

“In practical animal behaviour the two sets of processes are pro-
bably more or less constantly interwoven, the higher activities (supra-
granular layer) coming to the aid of the lower as far as the capability
of the animal allows. In the case of the lower mammals (e.g. insecti-
vora) the limits of this capability are comparatively soon reached,
and correspondingly these mammals possess a relatively poor supra-
granular layer. Many of these lower mammals have adopted a safe }
mode of life, others have resorted to fecundity. With these, which
may, for present purposes, be termed extraneous aids to survival,
their essentially instinctive activities have been relatively sufficient
to ensure their continued existence. There has, therefore, in these
mammals, been little necessity for the development of a supra-granular
layer, the infra-granular portion of the pallium providing most of the
necessary cortical physical basis required for practical behaviour. 4

“The infra-granular layers, with the reservation to which refer-
ence has been made, thus constitute the earlier developed and more
fundamental associational system of the cerebral cortex; the supra-
granular layer, a higher and accessory system superadded, and of
any considerable functional importance only in certain regions in
lower mammals, such as the insectivora.”

Before the question of cortical localisation receives attention, an
important communication by Mott (1904), on the progressive evolu-
tion of the structure and functions of the visual cortex in mammalia,
calls for reference, as a prominent feature of the article is the con-
sideration paid to the cell lamination of the visuo-sensory and visuo-
psychic regions. The paper deals with the subject from not only

ON THE FUNCTIONS OF THE CEREBRUM 299

the histological but also the clinico-anatomical and experimental
aspects, and contains a mass of interesting information. The author
_ describes the visual cortex of the insectivora, rodents, marsupials,
ungulates, carnivora, lemurs, and primates. He arrives at the
following conclusions :—

“There is a correlation of structure and function as exhibited by
a progressive complexity of cell lamination of the visual cortex in
mammalia from the insectivora to primates. The more the animal
depends on vision as a directive faculty in its preservation the more
complex is the structure.

“The transition of uniocular panoramic to perfect binocular
stereoscopic vision shows successive stages in the number of direct
fibres until, in the primates, there is semidecussation and, as far as
my observations go, this may be correlated with a progressive develop-
ment in the layer of higher associational pyramidal cells lying above
the layer of granules.

“The progressive evolution of vision as a directive faculty is
simultaneous with a motor adaptation, especially related to the mode
of feeding and defence rather than to a particular species.

“ Carnivorous animals, especially cats, therefore, have their eyes set
forward, abundant direct fibres, and good binocular vision, to enable
them to seize their rapidly moving prey with their teeth or paw.

“ Better motor adaptation, as Sherrington has independently
suggested from his flicker observations, then is probably the essential
cause of the direct path of the optic fibres and binocular vision.

“It is, however, in the primates that we have semidecussation
of the optic fibres, a macula lutea, eye movements in all directions
independent of head movements. Convergence and perfect binocular .
stereoscopic vision associated with the hand, which, in the apes, be-
comes the principal executive agent in the procuring of food, defence,
and flight. Visual images are now always associated with impressions
| of the exploring hand, and the ideas of form, substance, extension,
~ and qualities of objects are the: complex of the visual and tactile
kinesthetic images, and capable of endless variations. This we may
connect with the appearance in the zoological series of an occipital
lobe, a line of Gennari visible to the naked eye, a deep layer of
pyramids with a double layer of granules in the visuo-sensory striate
| area. But even more important than this is the appearance of a

definite associational zone in which there is a much greater depth
F of pyramidal cells, the third layer of which is characterised by very
large pyramids serving as higher complex association neurones between
the visual cortex and the auditory and tactile motor areas. As we

re
300 RESEARCHES ON CORTICAL LOCALISATION AND

rise in the scale of primates this associational zone increases with
the more perfect specialisation of the fore-limbs for manipulation
and the erect posture, and this we may correlate with the increase
in area of the associational or visuo-psychic zone, the increasing
development of the parietal lobe, and the pushing back and infolding
of the striate visuo-sensory cortex, so that in the highest types of
man it comes to occupy the infolded calcarine region of the mesial
strface, although some lower types still preserve the anthropoidal
character. It is probable that the same causes give rise to the shifting
forward of the anterior motor eye centres.”

In this connection reference may be made to a paper by Wilfred
Harris. This writer discusses the question of binocular and stereo-
scopic vision in man and other vertebrates, with regard to the de- ~
cussation of the optic nerves, ocular movements, and the pupil light
reflex.

CorTICAL LOCALISATION BY MEANS OF THE HISTOLOGICAL
METHOD

The researches of Flechsig on the development of the human
brain by a study of the process of myelination are so well known
to neurologists that any description of them may seem superfluous.

The conclusions at which he arrived are, however, of funda-
mental importance, and form the origin, if not entirely the basis,
of our present knowledge of cortical localisation by histological
methods. Again, his generalisations in the gross have success-
fully passed through a storm of discussion and dissent which is
almost unsurpassed in the history of research. Lastly, even at
the present time, except by neurologists, the researches of Flechsig
are by no means as generally understood and appreciated as they
merit. A short description of the main features of the investiga-
tions of this writer is therefore perhaps not entirely out of place
as an introduction to the subject under consideration.

By studying the exact period of myelination of different parts
of the cerebrum in the human fetus and infant, Flechsig was
enabled to divide the cortex cerebri into the two great classes
of “sensory centres”?\and “centres of association.” The former
myelinate earlier than the latter, and possess a well-marked system
of fibres of projection. ‘The latter myelinate later and are rich in
long systems of fibres of association. The difference is really one

of degree only, as Flechsig does not deny that fibres of projection

ON THE FUNCTIONS OF THE CEREBRUM — 301

exist in the association centres, and that association systems exist
in the sensory spheres.

In the whole cerebrum he described in 1898 no less than forty
separate myelogenetic fields which develop at different periods.
In 1901 he reduced these to thirty-six, and in 1903 he made no
alteration in the number although he stated that later investi-
gation might eventually cause him to do so.

Of the sensory spheres he describes four, namely, for (1) bodily
sensibility ; (2) visual; (3) auditory ; and (4) olfactory and gus-
tatory sensations. (1) has eight separate myelogenetic fields, and
each of the others has three each.

Of the centres of association he originally described four, namely,
the frontal, the parietal, the temporal, and the insular. Later he
combined the temporal and parietal centres into one, the great
posterior centre of association. In 1900, however, owing to his
discovery of a centre of projection in the gyrus subangularis, he

again separated these centres.

In Fig. 2 these sensory spheres and centres of association are
indicated.

In the temporal and parietal centres of association there exist,
according to Flechsig, peripheral zones, which develop earlier, and
central zones, which develop later; the former adjoin the sensory
centres, and are united to them by numerous arcuate fibres.

In the frontal centre of association similar zones exist, but
their disposition is much more complex.

The insular centre of association, and also that in the precuneus,
consist of peripheral zones only. Flechsig is of opinion that the
peripheral zones may be intermediate types between the central
territories of association and the sensory projection spheres.

Hence, of the centres of association, the frontal exhibits the

_ greatest complexity, the temporal and. parietal are intermediate in
structure, and the insular and that in the precuneus are the least
complex of the types.

ee ee ee el _— — =

Flechsig’s views on the functions of the central territories of the
areas of association are as follows: “ The central territories of the
zones of association (especially the middle of the angular gyrus, the
third temporal convolution, and the anterior half of the second frontal
convolution) are apparently the nodal points of the long systems of
association, whilst the peripheral zones only feebly show these char-

fa

-
‘

302 RESEARCHES ON CORTICAL LOCALISATION AND

“The central territories are terminal territories; they are essen-
tially characteristic of the human brain. Isolated destruction of *
these is never accompanied by phenomena pointing to disturbance

e sibility Project;
a of = On Cenp,,

UONeDosse
U9 Ieju08y

JO

gustatory projection
centre ; 7

a/ -
Centre of association

any sensibility Projecti
g0 - *

void

ye1gOSse

uote!
yo 243492 189

_ Visual
projection centre

Insular centre
of association

projection
: n
Parietal and temporal oe

céntres of association

Fic. 2 (after Flechsig).—In these diagrams the ‘‘centres of projection” and
‘centres of association” are mapped out according to Flechsig. The small dots

are placed in the chief focus of each centre of projection. Around these chief foci »
are the regions to which a smaller number of fibres of projection pass ; these are 4
indicated by larger dots. These figures, which represent the different cortical |

spheres indicated by Flechsig ‘as the result of his embryological studies, should be
compared with Figs. 3 and 4, and 5 and 6, which illustrate the various areas into
which the adult cerebral cortex has been subdivided by Campbell and Brodmann
respectively.

of motion or sensation. Motor phenomena, which occasionally
accompany lesions of these territories, must be interpreted as actions
a distance,

“The central territories of the zones of association. are in more

ON THE FUNCTIONS OF THE CEREBRUM 303

or less direct relationship, each with several sensorial zones, some
with all.

“ After their bilateral removal intelligence is affected, and especi-
ally is association of ideas interrupted. These central territories are
thus probably of great importance for the exercise of intellectual
activity, for the formation of mental images composed of several
sensory qualities, for the accomplishment of arts, such as the naming
of objects, speaking, &c. These functions are especially interfered
with in affections of the posterior centres of association. Clinical
observation establishes this fact, and thus justifies the legitimacy
of our division of the cerebral cortex into sensory centres (centres of
projection) and centres of association.” (Archiv de Neurologie, i.,
- 1900, pp. 337-338.)

The views of Flechsig were severely criticised by Hitzig, who,
4 however, is disposed to admit their general truth in a less positive
form; and by Vogt, who directly contradicted many of Flechsig’s
conclusions, and especially the thesis of the constancy and regu-
larity of myelination of the different systems of fibres. He is
inclined to look upon the majority of either early or late
myelinated fibres as projection fibres, and he regards the method
of Flechsig, though not valueless, as inferior to the more recent
methods of Campbell and Brodmann and himself, namely, the
. study of the cell and fibre architecture of the adult cerebrum.
Monakow, in his criticism, drew attention to the small proportion
which the projection fibres form of the total mass of cortical fibres

| of any of the convolutions, and he thinks that it is not possible,
however roughly it be done, to define the regions which are poor.

in these fibres and those which are abundantly supplied with them.

Sachs, whilst admitting that the sense centres are sharply defined

off at an early period from the rest of the cortex, considered it
impossible to prove later, when myelination has advanced, that
medullated projection fibres do not pass to the centres of associa-

tion. Bianchi also has for many years strongly combated the
generalisations of Flechsig. He is not satisfied that myelination

of the various bundles of cortical fibres follows a constant law or

- occurs in a regular sequence. He denies that the phenomena of
anatomical evolution need necessarily presuppose the existence
of functional activity of corresponding grade. He remarks, for
example, that there may be complete myelination of the supposed
centre for reading in the brain of an imbecile who has never learned

|

S “ea
304 RESEARCHES ON CORTICAL LOCALISATION AND —

toread. He is of the opinion that the only region of the brain which
can be regarded as purely associational in function is the prefrontal
area, which is generally acknowledged to possess no fibres of pro-
jection; and, excluding the language zone, he considers that the
whole post- and infra-Rolandic portion of the cortex cerebri is
perceptive in function. ‘One can symbolise the cerebral mantle
as a state with a representative system—a parliament and govern-
ment. The mantellar parliament would be constituted by the
perceptive zones. . . . The central government would be repre-
sented by the frontal lobes.” (Textbook, 1906, p. 172.) Bianchi,
in other words, denies that the post- and infra-Rolandic parts of
the cerebrum can be subdivided into areas of projection and zones
of association.

As a general statement it may be remarked that the conclusions
of Flechsig, in their essential features, have been widely accepted,
and that, whilst the projection areas, as has been already pointed
out, probably occupy neither the identical position nor the same
extent of cortex in the adult brain that they do in the foetus and
infant, it may be assumed.that a great parieto-temporal centre
of association exists posteriorly, and a more complex prefrontal
centre of association anteriorly, the insular and precuneal centres
being less complex in type, and probably of less importance, than
either of the former.

After this introduction to the question in its more general
aspects, the subject of cortical localisation by histological methods
will now be considered in detail.

The first important paper on cortical localisation was that of
Bevan Lewis and Henry Clarke, published in 1878, on the cortical
localisation of the motor area of the brain. This communication, ~
which localised the motor area in front of the furrow of Rolando,
attracted little attention owing to the fact that the conclusions
contained in it were opposed to the results of the numerous
physiological experiments which, during the last two decades of
the nineteenth century, largely monopolised the field of inquiry
into the functions of the cerebrum. The observations of Lewis
and Clarke have, however, at last obtained complete if belated
recognition in consequence of the experimental work of Sherrington
and Griinbaum, recently confirmed by Oscar Vogt, and the his-
’ tological researches of Campbell and of Brodmann. It is an
interesting and in many respects a fortunate fact that the experi-

ON THE FUNCTIONS OF THE CEREBRUM — 305

mental method, which was responsible for the non-recognition of
an important contribution to our knowledge, was also the method
which first supplied evidence of its truth.

With the exception of the elaborate cell and lamination studies
| of Hammarberg, which were published posthumously in 1895, and
, of a paper by Schlapp in 1898 on the cortex of the ape, no con-
tributions of direct interest appeared until the year 1900, when

the present writer communicated his paper on the exact histo-
logical localisation of the visual area of the human cerebral
cortex.

In this paper the exact limits of the human “ visuo-sensory
area’ were mapped out in six hemispheres derived from persons
with normal vision and from cases of long-standing and congenital
blindness, and the surrounding zone of cortex, the lamination of
which was unaffected by the absence of vision, was described
under the term “ visuo-psychic.”

The limits given to the former area indicated the approximate
truth of the opinion at this time held by Henschen and supported
by the embryological researches of Flechsig and the clinico-patho-
logical investigations of Seguin, Vialet, and others; and their
correctness has since been confirmed by Campbell, Brodmann,
Elliot Smith, and many other investigators.

: Since this paper was published, numerous contributions have
appeared on the subject of cortical localisation by the histological
method.

Of these the chief are by Brodmann (1902-1907), Campbell (1905), .
W. Kolmer (1901), Hermanides and Képpen (1903), Képpen and
Lowenstein (1905), Elliott Smith (1904-1907), O. Vogt (1906), Mott
(1907), G. A. Watson (1907), and Mott and Kelley (1908).

. In these papers the whole cortex’in many orders of mammals
has been mapped out into various histologically different regions,
but, except in the case of the psychomotor and visuo-sensory
areas, experimental or histo-pathological proof of the function of
these regions is not yet complete.

The most elaborate of these researches are those of Brodmann
and of Campbell. These authors have independently mapped out
into histologically different areas the whole human cortex cerebri,

as well as the cortex cerebri of many orders of mammals. Owing
. U

——

306 RESEARCHES ON CORTICAL LOCALISATION AND

to the great importance of the subject, which, however, it must
be remarked, is still in its infancy, the human maps of these
investigators are reproduced here as Figs. 3, 4, 5, and 6.

As might be expected in the case of such elaborate and totally
independent investigations, and in view of the great difficulties
involved in the cutting up, blocking, sectioning, orientating, and
reproducing in diagram form of the cortex of entire human hemi-
spheres, the maps given by Brodmann and by Campbell differ
considerably in detail from one another.

They agree with one another, on the other hand, much more
than either of them resembles the maps of Flechsig (see Fig. 2).
It must not be forgotten, however, that the diagrams of Flechsig
indicate the projection areas of the foetus, which there is reason
to suppose differ considerably in distribution from those existing
in the adult. This difference is due to the increased development —
of the later evolved associational spheres in the latter, which
affects both the position and the relative size of the earlier evolved
projection spheres. For example, Flechsig’s area for bodily sensi-
bility is both pre- and post-Rolandic, although he states that the
majority of the projection fibres pass behind the central fissure.
In the adult it is at least probable that this projection area is
entirely post-Rolandic; and it is known that the psychomotor
area is pre-Rolandic. At the period when the latter area was
considered to be both pre- and post-Rolandic, and to be sensori-
motor in function, its supposed distribution closely resembled the
foetal: bodily sensibility area of Flechsig; and the two were re-
garded as identical. The maps of Brodmann and of Campbell
must not therefore be regarded as impugning the general accuracy
of the diagrams of Flechsig with regard to the projection areas of
the foetus.

It may be remarked that in only two regions are the maps of
Brodmann and of Campbell in complete accord, namely, in the
psychomotor or Betz cell area (4 of Brodmann and “ precentral ”
of Campbell), and the visuo-sensory area (17 of Brodmann
and “ visuo-sensory”” of Campbell). The former of these is the
area mapped out by Lewis and Clarke (1878), and the latter is
that mapped out by the writer (1900). The extent of the visuo-
psychic region (18 of Brodmann), which was described by the
present writer as surrounding the visuo-sensory area, but was not
more closely defined owing to its somewhat indefinite limits,

Ms

ON THE FUNCTIONS OF THE CEREBRUM 307

Whi .
} oa WHS Z _ i
vi » GN ZA :
nwo AN <
Visuo- ‘ 2S > . <et
prychsc f y Z WY) hy Sos
' i} ; errs, 4 °

Visuo-

a
ee oe
= = =)

=

Fig. 4 (Campbell, 1905).

308 RESEARCHES ON CORTICAL LOCALISATION AND

2)
44a ‘F32;
RI GAR AACA
88 =

Fic. 6 (Brodmann, 1902-1907).

ON THE FUNCTIONS OF THE CEREBRUM = 309

is given so differently by Brodmann and by Campbell that it
might appear that no advance had been made on his original
description. A careful study of the maps of Brodmann and of
Campbell in the light of the writer’s special knowledge of the

histological characters of several portions of the cortex cerebri has,

however, convinced him that the more elaborately detailed map
of the former of these investigators is the more correct. In support
of this statement he would refer to the recent paper of Gordon
Holmes on the histology of the post-central gyrus, in which the
findings of Brodmann are confirmed. —~

The writer is, however, of the opinion that, whilst further histo-
logical research will undoubtedly enable certain other projection
areas to be as precisely defined as have been the psychomotor
and visuo-sensory areas (even if Brodmann’s findings in those
respects should not be confirmed in their entirety), the exact
differentiation of the remainder and greater portion of the grey
mantle into equally precise areas will be attended with great
difficulty owing to the probability that considerable differences
exist in the case of different individuals. He nevertheless regards
such precise differentiation as possible, and considers that light
will in the future be thrown on the histo-pathology of amentia or
cerebral sub-evolution by this means. For example, in the six
occipital regions mapped out by the writer in the paper already
referred to, the shape and apparent extent of the visuo-sensory
area exhibit considerable individual differences quite apart from
the questions of age and blindness. As such differences exist in
a projection area, it is probable that more marked variations will
occur in the case of the later specialised areas of different brains.
Though fissuration and histological differentiation do not run hand
in hand, the researches of Karplus on the fissuration of the human
cerebrum with regard to family likeness are worthy of mention in
this connection.

Beyond a relatively gross. subdivision of the cerebral cortex
into different areas, it is unlikely that the histological method
will be of assistance, as cerebral function, even when relatively
low in grade, consists of associational processes which involve
many related regions of the cortex. Further, as is shown espe-
cially by the study of sense deprivation, the maimed brains of
patients suffering from this disability are capable, to a remarkable
extent, of replacing the normal methods of association by dis-

310 RESEARCHES ON CORTICAL LOCALISATION AND

similar, though related, modes which in many instances fulfil their
purpose in an admirable manner.

Hence, the histological investigation of a given cerebrum is
probably capable of affording a rough criterion of the anatomical
basis which subserves, not the actual grade of functional activity,
but the possible limits of educability of the organ. It may be re-
marked that this mode of viewing the subject disposes of the chief
objection urged by Bianchi against the doctrine of Flechsig.

It may therefore be stated that.the exact limits of the psycho-
motor or Betz cell area, and of the visuo-sensory area, are known
beyond doubt, and that their functions have been proved by
experimental or histo-pathological methods. As regards the less
certainly defined visuo-psychic region, the associational, in contra-
distinction to receptive, function of this area has been develop-
mentally proved by facts stated earlier in this article. These
from a different aspect, that of the evolution of cortical lamina-
tion, confirm the doctrine of Flechsig with regard to centres of
association and of projection. A similar statement may be made
with regard to the well-known, but as yet not precisely defined,
prefrontal region of the cortex cerebri (10 of Brodmann). Further,
anatomical evidence points to the post-central gyrus or some part
of it as the projection area for bodily sensibility, and the recent
experiments of Oskar Vogt, who states that ablation of this gyrus
in the monkey is followed by ataxy without palsy, have finally
proved the truth of this view. There are anatomical grounds for
considering that the projection spheres for hearing and for olfactory
and gustatory sensations are more or less correctly located, but
experimental or histo-pathological proof in these cases is not yet
available. With regard to the numerous other areas mapped out
by Brodmann and by Campbell, there is little doubt that future
research will enable both their exact or variable limits to be
determined, and their functions to be finally proved.

It is ti: us possible to make the broad statement that the human
cerebral co.tex, excluding for the moment the frontal lobes, is
histologically differentiable into areas of projection connected with
the various senses, each of which areas possesses a zone of cortex
connected with or surrounding it, and into further areas which
- occupy the remainder of the cortex. Reasoning by homology on
the truths known with regard to the visuo-sensory and visuo-
psychic regions, it is possible to state that the areas of projection

ON THE FUNCTIONS OF THE CEREBRUM = 3il

are chiefly concerned with the reception of afferent impressions of
various kinds, and that the cortex in relation to each of these is
especially concerned with associational functions or psychic pro-
- cesses hall-marked by their several sensory areas. It may further
be provisionally stated that a large part of the remainder of the
cortex under consideration may probably be regarded as the
physical basis of language (not words, but word-groupings), 7.¢. a
mechanism for the symbolic integration of the various more or
less complex products of cerebral association. This question will
be considered later in connection with the subject of the higher
functions of the human cerebrum.

As regards the frontal lobes, but two regions call for especial
remark here, namely, the psychomotor area and the prefrontal
region.

With regard to the psychomotor area (‘ precentral” of Campbell,
4 of Brodmann), it is hardly necessary at the present time to
indicate the various reasons which prove that this area is asso-
ciational and not sensory in function, and that, in addition, it
possesses a direct efferent connection with the motor groups of
lower neurones.

The cerebral cortex may, in fact, be regarded as a complex
sensori-motor mechanism. Of this the non-frontal portion consists
of sensory areas (centres of projection) and of zones of association
of various types and grades of complexity. The frontal lobes, on
the other hand, contain the efferent portion of the mechanism.
The psychomotor area may be regarded as the lowest grade of
this, and as concerned on the one hand with the integration -
and on the other with the efferent transmission of the motor
expression of the associationally elaborated results of sensorial
stimulation.

The prefrontal region (10 of Bradmann) is the most complex
of the zones of association of Flechsig. It is the last portion of
the cortex to be evolved and the first to undergo retrogression.
The outer cell lamina or pyramidal layer of this region varies
directly in depth according to the mental power of the individual,
in the case of foetuses and infants, idiots and imbeciles, and chronic
* and recurrent lunatics without dementia. In cases of dementia,
degrees of retrogression occur which vary directly with the existing
grade of dementia. Finally this layer of the cortex is the only
layer which varies measurably in depth in normal individuals. On

312 RESEARCHES ON CORTICAL LOCALISATION AND

these grounds alone it is possible to assign to the prefrontal cortex
the highest and latest evolved functions of voluntary attention
and inhibition, and of selection and co-ordination of the various
individually complex processes of cerebral association. The pre-
frontal portion of the cortex is thus concerned in the performance
of the highest grades of cerebral function, and also bears to the
psychomotor area a similar relationship (though in the converse
direction as regards action) to that borne by the posterior regions
of association to the centres of projection.

To endeavour to indicate the functions of the cortex of the
intermediate portion of the frontal lobes would in the present
state of knowledge be to enter the realm of conjecture. It may,
however, be remarked that part of this associational zone un-

doubtedly contains the physical basis of the motor aspect of the _

mechanism of language, which is the instrument for the symbolic
integration of the various more or less complex processes of cerebral
association. Until the recent publication of the investigations of
Marie and of Monakow, Broca’s area was generally regarded, by
neurologists at least, as the region concerned with one portion of
this mechanism, namely, the “speech centre.”” Now, however, as
will be indicated later, a much broader view must be taken of
the complex mechanism of language, which possesses multifarious
associational connections with probably the whole cerebrum. The
mechanism of language must in fact be regarded, not merely as a
series of cortical centres, one or more of which may be blotted out
without more than local interference with the mental functions,
but as the absolutely essential factor to the so performance
of these.

With reference to the respective functions of the two greatest
centres of association, a large body of neurologists, notably Bastian,
Hughlings Jackson, Mott, Schifer, and Flechsig himself, are of
opinion that gross mental disabilities are more likely to occur in
lesions of the posterior centre than of the anterior, whilst Won
Hitzig, Ferrier, Bianchi, &c., hold the opposite view.

From the purely neunclogioal aspect, especially when con-
sidering the different varieties of “aphasia,” the former view
had undoubtedly much in its favour. For example, until quite
recently, cases of Wernicke’s (sensory) aphasia were generally
considered to exhibit gross mental disability, whilst cases of Broca’s
(motor) aphasia were supposed to be free from this symptom. The

-

,
:

ON THE FUNCTIONS OF THE CEREBRUM — 313

latter option i, however, disputed in toto by Marie, who has been
confirmed in his observations by numerous recent writers.

Premising, however, that the posterior centres of association
were concerned with processes of lower association alone, general
mental disability would still be evident in cases of gross lesion of
the hinder part of the hemispheres, as the patient would under
these circumstances be unable in many cases to produce satis-
factory evidence of general mental soundness. In many other
cases, also, such an entire disturbance of perceptive and ideational
processes as occurs, would be not unlikely to cause too great a
strain on the higher associational functions, and to directly result
in the development of symptoms of true mental alienation. This
is the result which actually ensues in many cases of sense depriva-
tion. It is further rendered probable by the fact that no less
than: one in every 280 of the general population is at the present
time suffering from mental alienation, and that the proportion of
potential psychopaths is very much greater. That this explana-
tion is correct is finally shown by the fact that the latest developed
and most complex portion of the human cerebrum, namely, the
prefrontal area, is, as has already been indicated, the region which
is especially affected in the subjects of mental disease.

Though it is not necessary to describe in detail the differences
in degree of development and in structure which exist between
the cerebrum of man and those of the anthropoid primates, it is
desirable, in this connection, to indicate here briefly the chief of
these. It consists, as may be seen by a study of the various
publications already indicated, in the immense development of the
anterior and posterior zones of association which has occurred in
the human brain. Concurrently with this increase in the extent
of the great zones of association there has developed in man the
power of abstract thought and the employment for this purpose
of highly complex articulate and written language. As the centres
of lower association in the anthropoid primates differ from those

of man in extent and complexity, so do the precepts of the former «* i

differ from the highly complex lower psychic units of the latter.
Equally does the rudimentary prefrontal region of the anthropoid
primates, which imperfectly marshals the relatively simple lower
psychic units of these animals, differ from the notable and still
developing prefrontal lobe of man, the capacity of which, for
co-ordinating the infinitely complex lower psychic units, which

Gene ~~ 7 » i

314 RESEARCHES ON CORTICAL LOCALISATION AND

are compounded in the human mind, into harmonious series of
concepts by means of voluntary attention and selection, is only
limited by the degree of functional development of this lobe in any
particular individual of the race. The lower associational centres
of man, which represent the physical basis of the content of mind,
are thus co-ordinate in development with the centre of higher
association and co-ordination, which represents the physical basis
of the capacity to voluntarily group into a harmonious and con-
nected sequence the higher psychic units of the mind.

Passing now from the highest to one of the lowest orders of
mammals, namely, the insectivora, one may obtain histological
evidence of equal importance with regard to the functions of the
cerebrum. Watson, in his recent paper, has mapped out the
minute brains of certain members of this order into histologically
different regions. Certain of these areas he regards as centres ~
of projection, and another, on the dorsal and mesial aspect, he
designates ,““ motor” from its histological structure. The: re-
mainder of the cortex, from the embryonic appearance of the —
cells contained in it, he designates “undifferentiated.” The
conclusions of Watson with regard to his investigation are best
expressed in his own words :—

4

“Tt seems necessary to assume that animals like the mole are
possessed of some means of simple sensory association, otherwise it
is probable that.the animal’s waking life would tend to be one of
almost continuous sensory confusion. Such association is called up
by the stimulation of one or other or more than one special sense,
and passes more or less directly to a motor or efferent result. This
appears to be the lowest grade of conscious neopallial association—
t.e. of psychic function—and it doubtless persists in mammals much
higher in the scale than the insectivora, and possibly in the highest,
though obscured in them by the development of a higher grade or
grades. It is not likely to exist as a random passing to and fro of
impulses from this sensory area to that, but to lie in some fusion zone.
Careful examination of the cortex of animals like the mole has failed
to reveal any ‘attempt at the development of a ‘psychic’ zone in
direct relation to any of the sensory projection spheres. The writer
does not consider that on histological grounds one is justified in
drawing close analogies between the areas he has termed ~“ undif-
ferentiated’ in the mole, &c., and the areas of cortex surrounding
the projection spheres in certain higher mammals. From the histo-

ON THE FUNCTIONS OF THE CEREBRUM — 315

logical aspect, therefore, the assumption that animals like the mole
possess any special areas of association, however small, appears to be
unjustified, and there is also, in view of the following remarks, some
reason for believing that such areas are in them physiologically unneces-
sary, in spite of the probable requirement by these animals of some
physical basis for simple sensory association.

“Dr. Bolton has suggested to the writer that in the mole and
similar animals the fusion zone for simple sensory impressions,
i.e. lowest grade of conscious association, lies in the area which has
been designated ‘motor.’ Taking the mole, for example, the areas
mapped out as kinesthetic, fifth sensory, visual, &c., are simple sensory
reception spheres for the respective senses, whilst area 1’’ (motor)
‘is the psychic equivalent of all these, and at the same time efferent.
Area 1” (motor) “‘ would thus receive impulses from each or all of the
sensory projection spheres and turn them into motor equivalents.
It is a general area of simple sensory association with the origin of
the efferent (motor) tracts included. This is as far as such an animal
as the mole has got in the direction of higher association. The struc-
ture of the cortex, however, even of this area, especially if regarded
as being of an associational type, is of a relatively elementary nature.

“The above suggestion does away with the apparent anomaly of
__ the relatively great extent of area 1’’ (motor) “if this be looked upon
as nothing more than a ‘ Betz cell’ region. It also coincides with
the fact that this area ranks with the best developed portion of the
cortex as regards supra-granular (pyramidal) layer which mammals
such as the mole possess, poor though this is.

“The writer’s views have been founded upon a study of the cortex
cerebri, not only in adult mammals but also in foetal and young animals.
He concludes that in the cerebral cortex of many—and probably of
all—adult lower mammals there are areas, considerable in extent, which
throughout life advance little—as regards complexity of their com-
ponent nerve cells—beyond their condition in the foetal or very young
animal. It is therefore on histological grounds presumed that such
areas are of comparatively little functional value to the animal.

“ He also considers it proved, as the result of the investigations
of Bolton and himself, that the structure of the neopallium is founded
upon an infra-granular basis. Further, it is suggested that in the
earliest attempts at evolution of structure which come to be of any
considerable functional value, the neopallium follows the plan of cor-
tical architecture long previously in the phylogenetic scale laid down
in the hippocampus, which plan in the latter situation has become
fixed, and, as a plan, permanent. The earliest and lowest grade of

316 RESEARCHES ON CORTICAL LOCALISATION AND

neopallial representation is thus, as regards structure, a repetition
of the hippocampal type—granular and infra-granular cortex. By
the accrescence of a supra-granular layer of varying degrees of depth ~
and complexity of its component nerve cells, different grades of repre-
sentation may be reached, and are reached to some extent in the
same animal, even if this occupies a lowly place in the mammalian
phylum, and to a greater extent the higher is the position in the scale .
to which the animal belongs.”

To summarise and correlate the mass of histological data which r
bears on mammalian cortical localisation from the aspect of
cerebral function would be beyond the scope of this article. Many ’
of the observations of the several authors differ greatly in detail, ,
as is naturally to be expected in the case of a subject still in its 7
infancy, and some are contradictory. Further, the greater part. ‘
of the published work deals with histological observations rather q
than with physiological deductions. It is thus not yet possible to ;
properly correlate the results of the various investigations which
deal with animal behaviour under different conditions, and the
deductions which may be drawn from them with regard to the
psychic processes which take place in the different members of
the various natural orders, with the histological data which have ;
hitherto been obtained with regard to the cerebra of the mammalia. ]

‘
:
EVOLUTION OF CEREBRAL FUNCTION q
:

The following broad statements, with regard to the mode of |
evolution of cerebral function, are, however,. possible, if they be
regarded in the light of a partially proved provisional hypothesis.

The term “ neopallium” has been introduced by Elliott Smith
to designate the cortex cerebri which is peculiar to mammals, and
which consists of a variable area intercalated between the pyriform
lobe and the hippocampus. This term is employed in contra-
distinction to the “ archipallium” of the lower vertebrates. The
neopallium increases in amount with the ascent of the mammalian
~ scale, and in man constitutes almost the whole of the cortex —
cerebri.

The functions of the neopallium are the reception of sensorial
stimuli, the conservation of associative memory, the performance
of the higher psychic processes, and the evolution.of the com- —

plicated motor phenomena, which depend on these, and which
serve as the sole objective indications of the performance of
psychic processes.

The neopallium is thus the highest sensori-motor ganglion of
the mammalia.

The archipallium is built on a basis which consists primarily
of but two cell lamin, which are homologous with the middle
(granule) and inner (polymorphous) cell lamine of the neopallium
(Turner, Watson). The neopallium is characterised by the ad-
ditional development of an outer (pyramidal) cell lamina, which
serves as the physical basis of “ psychic” in contradistinction to
“instinctive” processes. This cell lamina is barely present in
the neopallium of the lowest mammalia, and increases in depth
with the ascent of the mammalian scale (Brodmann, Watson).
It is earliest and also least developed in the projection areas, and
is later developed and more highly evolved in the regions con-
cerned with associational functions. The human brain is char-
acterised by the evolution of a prefrontal region of notable size,
and of great complexity of histological structure (Flechsig, Bolton,
Turner, Watson). The outer cell lamina of this region varies
measurably in depth in normal individuals, and in its degrees of
evolution and retrogression varies in depth according to the mental
capacity of the subjects of mental sub-evolution and dissolution.

In the earlier evolution of-the neopallium, certain projection
zones of simple structure exist, together with a rudimentary
“ motor” area, the function of which is to fuse the products of
the projection areas and turn them into motor equivalents. The
remainder of the cortex is embryonic in structure (Watson), and
is probably latent as regards functional activity.

During the ascent of the mammalian scale, the projection and

_ motor areas increase in complexity of structure (Brodmann, Elliott
Smith, Mott, &c.), and advance in functional activity. Until,
however, the carnivora are reached (Campbell), there is no indi-
cation of the development of histologically differentiable associa-
tional zones around or near the centres of projection. It is probable

that, in agreement with the relatively embryonic structure of the

test of the cortex, the functional activity of this is largely latent.

By the primates are reached, well-developed and histologically
differentiable zones of association exist in the neighbourhood of
_ the projection areas, and similarly developed cortex exists in front

ON THE FUNCTIONS OF THE CEREBRUM — 317

i bow

318 RESEARCHES ON CORTICAL LOCALISATION AND |

of the psychomotor area. The remainder of the cortex has largely
ceased to present embryonic features.

The cerebrum of the higher primates is thus characterised by
the evolution of regions of associational cortex, posteriorly be-
tween the projection areas, and anteriorly in front of the psycho-
motor area. The former is probably concerned with the higher
elaboration of the “sensorial,” and the latter with that of the
‘‘ motor” aspect of the cerebral functions.

In man the area of cortex devoted to associational functions
is enormously enlarged posteriorly, and is still more increased
anteriorly by the evolution of a notable prefrontal lobe. Con-
currently with this increase in the zones of association, language

has been evolved, from both “ sensorial” and “ motor” aspects, as ~
a complex mechanism for the symbolic integration of the various”

more or less individually complex products of cerebral associa-
tion; and the higher psychic functions, of voluntary attention
and inhibition, and of voluntary selection and co-ordination into
orderly sequence of the processes of lower cerebral association,
have been developed.

THE HicHEeR FUNCTIONS OF THE HUMAN CEREBRUM

The further consideration of the functions of the cerebrum,
namely, the description, or attempted description, of those func-
tions which are. peculiar to man, necessitates the passing of the
_border-line between physiology and psychology. Hitherto the
subject of aphasia has been regarded as a branch of the former
science, and has fallen under the purview of the neurologist.
Recent investigations, in particular those of Marie, have, however,
shown that a wider view must be taken of the relationship of
language to the psychic functions, and of the influence on
these of the disabilities which are described under the term

** aphasia.”

As a preliminary to the further consideration of the functions
of the cerebrum and to the description of these investigations, it
is therefore necessary, for the benefit of such readers as are not

versed in psychological terminology, to introduce here certain

general observations and definitions.
As has already been remarked, the cerebrum should be regan

as a great sensori-motor ganglion, the only objective indications —

7
‘

hg

ON THE FUNCTIONS OF THE CEREBRUM _ 319:

of the functions of which are derived from the various motor

exhibitions which are presented by its possessor.

In the lower animals these are of two kinds, evidences of feeling
or emotion, and evidences of intelligent (instinctive or acquired)
activity ; and either of these may be partly indicated by means of
articulatory exhibitions.

The same evidences of cerebral activity are presented by man,

in whom, however, the indications of emotion are more numerous
and complex, and the evidences of psychomotor activity are in-
finitely more elaborate. The latter, apart from the ordinary motor
indications of intelligence, consist of gestures and of spoken and
written language.
_ Any discussion of the theory of the emotions would be out of
place in this article, but it may be indicated in passing that they
are probably evolved from the lower or instinctive plane of motor
exhibition. This is suggested by the common observation that
very young infants “ make faces” indicative of various emotions
under the influence of gastro-intestinal irritation, long before they
present evidence of intelligent motor activity, and still longer
before they are able to articulate a word. Further, objective in-
- dications of probably experienced emotions become well-developed
in infants at a time when the ordinary motor indications of intelli-
gence are still highly inco-ordinate.

Of the indications of human psychic activity, the most im-
portant, namely, language, will now be considered.

The elements on which cerebral activity is based are the various
sensory impressions which arrive at the cortex and which are con-
served there as sensori-memorial images. These elements form
the raw material of the psychic processes and are spoken of as
sensations. To be understood, sensations require localisation in
_ space and reference to the objects from which they arise. The
cerebral process involved in the preliminary fusion of sensations
is spoken of as perception. For example, the sound of a clock
ticking results in the localisation of the sensation in a certain
direction and to a particular object, the clock. Not only, however,
does the process of perception involve the fusion of direct sen-
sations, but it also necessitates the awakening and fusion with
these of sensori-memorial images of former sensations. In the act
of identifying an object, e.g. a locomotive, the various sensations

arising from it awaken a variable number of sensori-memorial

ee ‘ 5 = ‘ zy

-

320 RESEARCHES ON CORTICAL LOCALISATION AND

images. Again, the sound of the word “horse ” awakens certain
sensori-memorial images, which may be of any type, from the
written word “ horse” to the last horse we have seen.

The presentation of a sensation, therefore, results in a cerebral
process which evolves the psychic product termed a percept.
This cerebral process necessarily varies on each occasion on which
it occurs. The word “ microscope,” for example, heard at different
times, evokes numerous related but dissimilar sensori-memorial
images.

Perception, therefore, is a cerebral process which is-similarin
nature but differs in detail on each occasion on which it occurs.
It is thus incorrect to speak of a cerebral centre for percepts,
which are psychic products that, except by accident, need never
be identical even if the arousing sensation is the same.

It may be remarked that perception can hardly be described as ©
the act of naming objects, for it is as often the reverse, namely,
the act of applying one or more sensori-memorial images to a
name; or the identifying of a sensation with a sensori-memorial _
image. The last corresponds to the crude perceptions of animals :
the others to perceptions involving the employment of the symbolic
mechanism of language.

The next grade of complexity of cerebral processes which is
rendered possible by the aid of language is the formation of a
concept or general notion, e.g. the evolution of a general name
such as animal, man, building. The psychic product is termed a
concept, and the process of conception involves the revivification
‘of numerous sensori-memorial images which present common
points of similarity.

The cerebral process involved becomes still more complex for
the evolution of such “abstract concepts” as heaviness, beauty,
religion.

It is at once evident that the process of conception, whether
it takes the form of generalisation from a series of sensori-memorial
images to a general name, or of revivification of a series of sensori-
memorial images in order that the meaning of a general name may
be interpreted, is a very complex one; and necessarily differs in
detail, in spite of a general similarity in nature, on each occasion
on which it occurs. It is thus incorrect to speak of a cerebral
centre for concepts.

A physical basis for the several words which symbolise the

ON THE FUNCTIONS OF THE CEREBRUM 321

variable cerebral processes termed conception undoubtedly exists
in the cortex cerebri. Common or abstract names, however, are
not concepts, but are merely symbols which enable former active
processes of conception to be recorded, and future acts of con-
ception to be evolved.

Proper, common, and abstract nouns may thus be compared in
function to the algebraic symbols employed by mathematicians,
whilst sensori-memorial images and crude sensations may be
compared to the numerals of arithmetic.

Language is, however, an infinitely more complex symbolic
system than is that employed by mathematicians; and its
“numerals,” 7.e. its sensori-memorial images and crude sensa-
tions, are innumerable.

As will be indicated later, the complete performance of the
respective psychic processes, with the resulting reintegration of
the particular percepts or concepts of which words are symbolic,
does not necessarily occur during the mechanical employment
of the language mechanism. Rowland, in fact, in her investiga-
tion of the psychological experiences connected with the different
parts of speech, distinguishes three stages of meaning—(1) A feeling
. of familiarity with the word ; (2) a feeling that she would know how
to use it; and (3) the unrolling of the images. The paper of this
author, which includes a valuable bibliography, is well worthy of
study in this connection. :

The cerebrum possesses an almost infinite capacity for the
development of symbolic systems. New languages may be ac-
quired, and as if on the principle of “the more the merrier,” with
each new acquisition the process of further acquirement appears
to become easier. The numerous skilled psychomotor perform-
ances which only compare with language in variety and complexity,
eg. music, painting, sculpture, &c., may also be indicated as allied
in nature to, though lower in grade than, the symbolic systems of
language and mathematics.

The language mechanism, like the routine systems and “red
tape” of every-day life, whilst a good servant, tends to become a
bad master, unless the cerebral processes necessary for the elucida-
tion of the meaning of the words employed are continually being
voluntarily performed. It is thus especially necessary, during
the voluntary employment of written or spoken language for the
evolution and reproduction of the highest psychic products, e.g.

2 7 =

“=n

322 RESEARCHES ON CORTICAL LOCALISATION AND

abstract thought, to continually revert to concrete examples. —
Many results of the higher reasoning processes would in fact be
quite unintelligible to the reader in the absence of concrete illus-
tration, and, what is even more important, the author himself
would not infrequently find a tortoise successful in its race with a
hare. Philosophic disputes have as a rule depended largely on
questions of definition, or on the employment of the same words
under slightly different connotations. Forms of words are worse
than useless unless their exact meaning is appreciated, and many
discussions and disputes have arisen owing to the critic holding
strictly to these, and thereby rendering it difficult or impossible
for their originator to make his intentions quite clear and in-
telligible.

The necessarily imperfect employment of the language
mechanism, owing to the occasional impossibility of satisfactorily
discovering a form of words in which to clearly express the exact
meaning of the writer or speaker, is in fact one of the most fruitful |
sources of disputation. It is not intended to imply by this remark
that such a person knows what he wishes to express. He is aware |
that the phrases he employs do not express what he desires, and |
at times his uncompleted cerebral processes may reach their goal
through the suggestion by another individual of a suitable form (
of words.

On the other hand, from the purely didactic aspect, a speaker .
occasionally finds his only safe refuge in generalities which are
capable of varied interpretation. Many a sermon is acceptable
to, and is approved by, a congregation, which would be up in
arms if the preacher produced concrete illustrations of his meaning,
e.g. his views with regard to certain political questions, &c.

The nature and mode of employment of the symbolic mechanism
of language will now be briefly discussed.

The whole of the higher intellectual processes are dependent
on, and develop pari passu with, the evolution of language. Till
of recent years the majority of, and even now many, individuals
depend on the sense of hearing for the acquisition of the greater
portion of their (human) psychic content, though persons who read
and write perhaps gain an equal amount by means of the sense
of sight, and the more intellectual members of the race probably
acquire the greater part by means of the latter sense. It may, —
however, be remarked that in some normal intelligent reading-

°

ON THE FUNCTIONS OF THE CEREBRUM 323

_- and-writing individuals visual association, and in others auditory

association, is the more natural method of acquisition.

Language, therefore, as the instrument of thought, or even as
its compeer, for the higher refinements of thought depend so
entirely on, and draw so much of their inspiration from, the
possession of a highly elaborate vocabulary, is of fundamental
importance for the performance of the higher, as of the less
complex, psychic functions.

Language, according to the type of sensorial or sensori-motor
avenues through which it is acquired and stored, and by means of
which it is employed, possesses four chief physical bases in the
cerebral cortex, namely, the auditory, visual, cheirographic, and
articulatory. For the sake of simplicity no attempt is made to
separate the kinesthetic from the purely motor divisions of the
latter two, though, in fact, it may be regarded as certain that these
are differently located. The kinesthetic divisions, are, however,
those which are at present under reference. All these “ word-
centres” naturally lie in or near the auditory, visual, and general
sensory projection spheres of the cortex, as words merely constitute
one variety of sensorial impression. It might therefore be sup-
. posed that loss of any one of the four afferent avenues to these
physical bases of language would not, owing to the commissural
connections between the several spheres, be of serious import,
apart from the non-reception of sensations through the absent
channel. That such a view is incorrect can, however, readily be
demonstrated. The spheres referred to, with their commissural
connections and their afferent and efferent projection systems,
merely form a convenient mechanism for the mechanical acquisi-
tion and reproduction of language, which would be meaningless
unless during the employment of its mechanism there occurred
an active associational participation on the part of practically the
whole mantle of the cerebrum.

A word, per se, represents merely an auditory or visual sensation,
or a cheirographic or articulatory kinesthetic impression, unless
it is employed as a symbol on which to integrate the percept or
concept which it signifies; and for this the cerebral mechanisms
or associational systems connecting the different projection and
sensori-memorial regions of the cortex are needed.

Further, both these developed percepts and concepts, and
also the associational processes involved in their formation, differ

~
. +

324 RESEARCHES ON CORTICAL LOCALISATION AND

not fundamentally but in detail on every occasion on which they
are evolved or employed.

Words may arise into consciousness through any of the
four language spheres. When, however, they are voluntarily and
silently reproduced, 7.e. thought of, words are invariably awakened |
through the articulatory word-centre under normal conditions. |
Further, this reproduction requires a muscular effort, and cannot |
take place without a definite articulatory attempt, usually, but
not necessarily accompanied by a slight expiration. Again, words
cannot be voluntarily repeated in thought by means of the cheiro-
graphic centre if the hand is not actually moved, unless such hand-
movements are replaced by slight movements of the head, or even
of the lower jaw or the eyes, through the agency of their respective
motor spheres. Such observations as have just been indicated
are valuable because they render it probable that the important
factors in the reproduction are not the muscular movements but
the sensorial impulses derived from these ; otherwise there is no
reason why such muscular movements should not be imagined
without any attempt at their actual performance. If words should
spontaneously arise in the visual or the auditory word-centre, the |
condition is so abnormal as to constitute a hallucination, which
the subject may or may not be able to distinguish from a true
visual or auditory sensation. A homologous phenomenon to such
a hallucination may be observed during the stimulation of the
psychomotor area of a monkey which has recovered from anesthesia. .
Such an animal regards the movement, say of the arm, with great
surprise, and at once performs a voluntary and opposite movement,
exactly as if the limb had been moved by an external agency.

There is thus reason to consider that words invariably arise
into consciousness by sensorial or sensori-memorial, and not by
psychomotor, means ; and the observation that normally they are
voluntarily awakened by the preliminary aid of the psychomotor
area is of significance with regard to the thesis that the frontal
lobes are concerned with psychic function from the higher asso-
ciational and also the motor aspect, and the remainder of the
cerebrum from the sensorial, sensori-memorial, and lower associa- —
\ tional.

However they arise into consciousness, words ‘naturally
possess very different symbolic values. Articles, pronouns, pre-
positions, conjunctions, interjections, and the simpler adjectives,

7%, } \ in — .- |

ON THE FUNCTIONS OF THE CEREBRUM — 325

adverbs and verbs, when thought of alone (articulatory word-
centre), as a rule arouse little beyond their respective visual
or auditory word-images, which, in themselves, are meaningless.
Adjectives, adverbs, verbs, and abstract nouns, when thought of
alone (articulatory word-centre), arouse first their respective visual
or auditory word-images. These, however, are meaningless until
by complex processes of association they are defined and illustrated
through the sensori-memorial spheres attached to the various
sensory or projection areas. Common or proper nouns, when
thought of alone (articulatory word-centre), may first arouse their
visual or auditory word-images, but they frequently at once awaken
a whole series of processes of association, and thereby determine
the reproduction of sensori-memorial images attached to one or
more of the several sensory or projection areas. It may be re-
marked that any such series of processes of association differs in
detail on each occasion on which it is evolved. For example, the
mental processes induced by the word “cat,” whether this be
thought of (articulatory sphere) or be heard or seen (auditory or
visual sphere), are different, not fundamentally but in detail, on
each occasion on which they are aroused. This ever-varying
perceptive content is consequent on the revivification of, and the
modification of the complex relations of, the numerous existing
sensori-memorial images, of which the word is symbolic, which
are constantly taking place under the influence of even apparently
unrelated afferent impressions.

Hence, the auditory, visual, cheirographic, and articulatory word-
centres merely signify the cortical regions in which lie the physical
bases of mental algebraic symbols. These, unless they serve as in-
citing agents from which spread, in different directions throughout
the cerebrum, complex impulses of association, signify no more than
_ unmeaning sounds, shapes, and musculo-kinesthetic sensations. _

Language is produced by the suitable co-ordination of the
verbal content of the auditory and articulatory word-centres. It
is originally acquired by imitation under the influence of audi-
tory sensations, and in educated persons language is more highly
evolved owing to education of the visual and cheirographic spheres.
When, however, it has once been acquired, language (¢.e. functional
activity of the several word-centres with their commissural systems)
is not necessarily employed as the instrument of thought, although
it has been primarily evolved for this purpose.

4

326 RESEARCHES ON CORTICAL LOCALISATION AND

Examples are common in which the mechanism of language is”
employed in a purely mechanical manner. Imbeciles can at times
learn by rote long paragraphs, of the meaning of which they are
ignorant. Children learn a large portion of their lessons in this
way. Adults, even, may learn the Lord’s. Prayer backwards, or
sentences in an unknown foreign tongue. Direct evidence of the
purely mechanical nature of these performances is often afforded
by the inability of the subjects to complete their feat, if they are
stopped during its course, unless they start again at the commence-
ment. Occasionally quite remarkable examples of mechanical
memory and of mechanical employment of the word-centres are
met with. From the former aspect may be mentioned the re-
production of long verbal or musical compositions after a single
reading or hearing, and from the latter the performances of “ cal-.
culating boys.” An interesting article on the latter subject has
recently been published by F. D. Mitchell.

Examples of this mode of employment of the language
mechanism may be readily drawn from every-day life. Many
word-complexes, which are frequently repeated, e.g. daily prayers,
are often gone through in a purely mechanical manner, whilst the
individual reproducing them is perhaps thinking of something
else. Again, it is appreciated by few that language, as normally
employed, is very largely a purely reflex, or, at any rate, automatic
function ; and that the significance of what is spoken is but feebly ©
appreciated by the speaker. In the majority of persons the word-
vocabulary which is in common use is very limited, and the phrase
vocabulary is both extremely limited, remarkably stereotyped,
and in many instances quite automatically | employed. In edu-
cated, and particularly in “well brought up” persons, on the
other hand, the word and phrase vocabularies, though equally
stereotyped) are much more extensive in range.

The voluntary employment of the language mechanism is
attended by greater executive difficulties than is the reflexly
induced and automatically performed mode which has just been
indicated ; and it is at times involuntarily incited, to the detri-
ment of the performer, by emotional disturbances. For example,
nervous persons, when in the presence of their real or imaginary, —
social or intellectual, superiors, speak haltingly and from a limited
vocabulary owing to the attempt to converse, not automatically,
but to order. On the other hand, in the voluntary employment

ON THE FUNCTIONS OF THE CEREBRUM = 327

‘of written or spoken language for the evolution and reproduction
of the highest psychic products, e.g. the production of an abstruse
thesis, the language mechanism is made use of solely for the pur-
pose for which it has been evolved, namely, as the instrument,
and the important assistant, of thought.

During the above observations an endeavour has been made
to indicate that language, though so commonly employed in a
largely automatic manner, and with but a feeble appreciation of
its signification, is nevertheless in essence a symbolic mechanism
for the integration of sensori-memorial images, and, though more
complex, is analogous, as an instrument, to the symbolic system
employed by mathematicians.

By its use it is the servant, and the necessary servant, of
thought ; by its abuse it becomes the compeer, or even the sup-
planter, of thought.

It is evident from the above considerations than any gross
structural or functional derangement of the language mechanism
must necessarily seriously impede, or even in certain cases pre-
vent, the adequate performance of those complex processes of
association which serve as the physical basis of the psychic
functions.

Apart from its general bearing on the higher functions of the
cerebrum, this discussion of the language mechanism has served a
further purpose, namely, the paving of the way to a clear under-
standing of the far-reaching importance of the investigations of
Marie on the subject of aphasia.

With the latter object in view, another allied subject will now
be considered, namely, the gross modifications of cerebral function
which are the necessary consequences of congenital or acquired
deprivation of the senses of hearing and sight. In cases of sense
_ deprivation, the structural and functional maiming of the cerebrum
concerns one or more of its earliest developed, most stable, and
functionally lowest parts, namely, the centres of projection. Such
lesions consequently present a simpler problem for study, in spite
of their far-reaching influence on the functions of the cerebrum,
than do the variable and often diffuse lesions which produce the
complex symptomatology of aphasia.

The senses of sight and hearing, especially the latter in un-
educated individuals, are so necessary to, and play such an im-
portant part in, both the evolution and the conservation of the

_
328 RESEARCHES ON CORTICAL LOCALISATION AND —

normal functions of the cerebrum, that deprivation of one or both
of these senses in congenital or early cases grossly modifies, and in
adult cases necessitates an entire readjustment of, the associa-
tional processes which constitute the physical basis of the psychic
functions.

In cases of deafness or blindness in which the deprivation is
congenital or is acquired in early life, the psychic functions are
either very imperfectly evolved, or are performed in an entirely
abnormal manner. In early or congenital deafness, the complex
mechanism for the reception, storage, and reproduction of lan-
guage, or the symbolic representation of the results of sensorial
excitation and of psychic association, is incapable of evolution,
unless the patients are laboriously educated through other avenues
of sensation. It is hardly necessary to add that mutism is a.
necessary consequence of this disability, though a considerable
development of lip-language can often be induced by education.
Such patients, in fact, unless educated by special methods, would
necessarily possess mental functions relatively little removed from ~
those of the lower primates. On the other hand, the congenital
or early blind can obtain a large and important part of their mental
content by means of the sense of hearing, just as do ordinary un-
educated (7.e. non-reading and non-writing) individuals. That
the former can supplement their methods for the acquisition and
communication of information by means of the deaf and dumb—
alphabet, &c., and the latter by means of the tactile motor sense,
does not affect the fundamental difference between them, which
is based on the fact that a highly important part of the mental
content is normally (in the uneducated) acquired by means of the
sense of hearing and not by that of sight.

In such cases deafness is therefore a more serious deprivation
than blindness, as, for the evolution of the functional activity of
the cerebrum, an entirely new development of associational spheres,
to replace those normally employed for auditory and spoken lan-
guage, has to be acquired. In the case of congenital or early
acquired blindness, on the other hand, the complex sphere of
language, with all its psychic components, can be employed in a
perfectly normal manner, and almost exactly as it is brought into
use in the case of persons who neither read nor write.

Deprivation of sight or hearing, when occurring later in life,
results, in the educated, in relatively less cerebral disability, and

ON THE FUNCTIONS OF THE CEREBRUM = 329

probably an approximately equal amount in the case of either
of these senses. In the uneducated, loss of hearing produces
greater cerebral disability than does loss of sight.

In all cases of acquired deafness or blindness, however, the
following results ensue. On the one hand, the patient suffers a
permanent loss of one or both of the important avenues of special
sensation, and on the other, all kinds and degrees of structural
and functional impairment develop in the cerebrum in conse-
quence of the deprivation. Not only does secondary atrophy of
the particular afferent fibres to the cerebrum result, but the com-
plex associational relations between the special projection area or
areas and the rest of the cerebrum are seriously affected. The
special sensori-memorial images dependent on the lost sense or
senses pass more and more into the sphere of the permanently sub-
conscious. The physical bases for the evolution of even the most
elementary (already experienced) percepts require readjustment to
the altered conditions. Finally, the mechanism for the development
of new and the correction and continuation of already experienced
percepts, which normally involves the majority of, if not all, the
projection or sensory areas of the cerebrum, together with their
related memorial spheres, becomes imperfect or “‘ maimed.”

In all these types, therefore, both sensory and also extensive
and grave associational deprivations exist; and the cerebrum,
as a machine, is maimed not’only in its most stable and earliest
acquired regions, namely, in one or more centres of projection
or sensory areas, but also throughout its intricate, later evolved,
and more important (from the psychic aspect) systems of lower
association.

Sense deprivation is, however, followed, in all, or nearly all,
early and congenital cases, and in many acquired cases, by still
more serious disturbances of the psychic functions than those
already indicated. In the former, imperfect evolution of the
higher functions of mind is usual if not invariable ; and in both
types dissolution of the centre of higher association, with conse-
quent dementia, is of common occurrence. In congenital cases
involution of the centre of higher association, with resulting
dementia, is eventually incited by the stress of prolonged sense
deprivation and the consequent abnormal modes of psychic asso-
ciation which result. In other words, the abnormally working
psychic machine sooner or later breaks down.

‘

330 RESEARCHES ON CORTICAL LOCALISATION AND

In persons who acquire sense deprivation later in life, the
mental stress involved on the one hand in the sense disability,
and on the other in the more or less unsuccessful attempts to
revive the related memories which tend to pass more and more
into the permanently subconscious, or to replace the absence of
these memories by the integration of percepts and concepts on
am unusual sensori-memorial basis, often, or perhaps invariably,
results in the development of irritability, or depression, or general
emotional instability. In rare cases like one cited by Clouston,
partial removal of the sense deprivation by operation (for cata-
ract) may result in a return to normal psychic life. In the case,
however, of individuals who possess higher cortical neurones of
deficient durability, insanity followed by dementia ensues.

It may finally be stated that cases of congenital or early
acquired deafness are more liable to imperfect mental development,
with which is associated mutism, than are cases of congenital or
early acquired blindness.

Further, both in the cases in which the sense deprivation is
congenital or acquired early in life, and in those in which it is
acquired after adult life has been reached, cerebral involution is
more likely to occur in the case of the deaf than in that of the
blind. This statement is supported by a series of cases which
were recently published by the writer, for, of the ten in the series,
three were deaf and dumb, two were deaf, four were almost or
totally deaf and blind, and only one, a well-marked high-grade
ament, who had been certified for thirty-seven years, was blind.

RECENT RESEARCHES ON APHASIA

The description of the language mechanism and the evidence
of its fundamental importance to the performance of the psychic
functions—especially that derived from the study of cases of
sense deprivation—have been given at considerable length. Whilst
the primary object of the writer has been the elucidation of the
manner in which the higher functions of the cerebrum are per-
formed, he has at the same time endeavoured to so present the
subject of language as to prepare the reader, not merely for the
appreciation of the gist of the recent researches on aphasia, but
for the acceptance of their results as truths of great importance.

The statements, that our views of aphasia require entire re-

ON THE FUNCTIONS OF THE CEREBRUM 331

vision, and that the time-honoured localisation of the motor speech

centre in the cortex of the posterior portion of the third frontal
gyrus (the speech area of Broca) is incorrect, are of so revolu-
tionary a nature that the reader may well require more evidence
of their truth than is afforded by the papers even of so renowned
a neurologist as Pierre Marie. Such evidence as can be derived
from the psycho-physiological study of the subject of language,
and from the results of recent research on cortical localisation and
cerebral function, the writer has endeavoured to produce.
Before indicating the views of Marie, it is desirable to refer
shortly to the theory of aphasia, advanced almost simultaneously
by Monakow in 1906. This investigator throws doubt on the
accepted localisation of the speech centre, and expresses the
opinion that aphasic disorders are caused less by destruction of
certain special regions of the cerebrum than by local losses of
functional continuity between the various centres which together
constitute the language mechanism. To this disturbance of
functional continuity he applies the term diaschisis. He indicates
that local affection of a connecting tract of fibres may cause tem-
porary suspension of the functions of one part of the mechanism
by removing from this the stimulus to action which normally
proceeds from another part. On the other hand, relatively inde-
pendent parts of the mechanism may pass into a state of abnormal
activity from lack of the controlling impulses which normally
proceed to them from other portions. Disturbances of local
function may thus arise in consequence of lesions situated in.
different parts of the brain.

This theory is propounded by Monakow to explain the frequent
discrepancies which exist between the clinical symptomatology
and the anatomical lesions of cases of aphasia.

He points out that many cases of aphasia occur in which search
for the expected lesion gives a negative result ; that a still larger’
number of cases recover although the lesion persists and even
becomes more extensive ; and that aphasic disorders often persist
in cases in which the lesion is found to be situated beyond the
limits of the speech area. He further remarks that “ sensory
aphasia” may occur with lesion of Broca’s gyrus, and “ motor
aphasia ” with lesion of the zone of Wernicke ; and that at times
the symptomatology varies greatly in cases in which the situation
and relations of the lesion are practically identical.

332 RESEARCHES ON CORTICAL LOCALISATION AND

The views of Monakow may thus be regarded as affording
a plausible explanation of the contrary and negative evidence,
with regard to the localisation of the speech-centre, which has
been published ever since the time of Charcot.

The articles of Pierre Marie, the first of which was published
some months earlier than the paper of Monakow, treat the subject
of aphasia in a more radical manner.

Marie, as the result of a study of the subject during a period
of ten years at the hospital at Bicétre, has expressed the opinion
that the whole of the accepted doctrines regarding aphasia require
reconsideration.

He distinguishes in the orthodox manner between “ motor
aphasia’ or the aphasia of Broca, “sensory aphasia” or the
aphasia of Wernicke, and “ anarthria” or the subcortical motor
aphasia of Déjérine.

In the first of these conditions the patient is usually described
as being unable to speak, although he understands what is said
to him, and as a rule retains his intellectual powers unimpaired.
In the second the patient is regarded as being able to speak in a
more or less intelligible manner, but to have more or less marked
impairment of intelligence. In the third, the only disability which
exists is loss or affection of the power of articulate speech.

In order to explain the views of Marie it is unnecessary to
consider in detail the various more or less complicated types of
symptomatology, which occur in cases of aphasia, and which are
readily classed under one or other of the aphasias of Broca and of
Wernicke. For such a description the reader is referred to the
various classical publications.

As the result of his investigations Marie considers that only
one form of true aphasia exists, namely, that of Wernicke, and
that the so-called “aphasia of Broca” is the “aphasia of Wer-
nicke ” + “ anarthria.”” He considers that Broca’s gyrus is not
concerned with the function of speech, that the “ area of Wernicke,”
namely, the supra-marginal and angular gyri, and the hinder
portions of the first and second temporo-sphenoidal gyri, is the
site of the lesion which causes true aphasia, and that a lesion of
the lenticular zone is the cause of anarthria.

Marie thus limits the lesion of aphasia to the region of the
cerebrum which has till of late been regarded as the seat of the
visual and auditory word-centres.

G

ON THE FUNCTIONS OF THE CEREBRUM — 333

Further, and this is the most important part of the doctrine,

Marie urges that in true aphasia intellectual impairment is
invariably present. “C'est quil y a chez les aphasiques
quelque chose de bien plus important et de bien plus grave
que la perte du sens des mots; il y a une diminution tres
marquée dans la capacité intellectuelle en général.” He considers
that the notion of intellectual impairment should dominate the
doctrine of aphasia.

He affirms that in all cases of the aphasias both of Broca and
of Wernicke there is a greater or lesser amount of difficulty in
the understanding of spoken language, and that evidence of definite
diminution of the intellectual powers can invariably be obtained
if the patients are properly studied. For this purpose he gives
his subjects complicated instructions. Instead, for example, of
telling the patient to cough, spit, put out his tongue, or shut his
eyes, he gives certain instructions of which the following two are
very commonly employed. “Of three pieces of paper of unequal
size which are placed on this table, you will give me the largest,
you will crumple up the medium one and throw it on the ground,
as to the least you will put it in your pocket.” ... “ You will
stand up, you will go and tap three times on the window with your
finger, then you will return before this table, you will walk round
your chair, and you will sit down.” He points out that, on
superficial observation, aphasics may appear to possess normal
intelligence, but that careful investigation readily enables their
defective mental powers to be determined. He gives, as an
illustration, a description of the blunders made by an aphasic who,
prior to the onset of his infirmity, had been a really good cook,
when he was provided with the necessary ingredients and instructed
to prepare an “ ceuf sur le plat” or fried egg. His account of the
incident is as follows :— ,

“Un de mes malades, atteint depuis des années d’une aphasie
d’intensité moyenne qui ne l’empéche d’ailleurs pas de se méler a
la vie commune, est un cuisinier, un bon cuisinier qui, sans aucun
doute, savait bien son métier. Je lui demandai un jour de me
faire un ‘ceuf sur le plat.’ Nous nous rendimes donc tous 4 la
cuisine, avec la surveillante qui devait remplir les fonctions
d’expert. La, devant le fourneau, on remit au malade les in-
grédients necessaires: un plat, un ceuf, du beurre, du poivre et du
sel et on lengagea & exercer ses talents. Cet homme hésite’ un

334 RESEARCHES ON CORTICAL LOCALISATION AND

moment, puis commet les solécismes suivants, qui nous sont au
fur et & mesure signalés par notre surveillante, passablement
scandalisée de voir un cuisinier se tirer aussi mal d’une épreuve
qui, pour une simple ménagére, n’efit été qu’un jeu: il commence
par casser son ceuf de fagon fort maladroite et le vide dans le plat
sans aucune précaution pour éviter de crever le jaune, puis il met
du beurre dans le plat, par-dessus l’ceuf, saupoudre de sel et de
poivre et met le tout au four. C’était la une faute capitale et la
surveillante nous fit remarquer qu'il avait fait l’inverse de ce qui
devait étre fait, le beurre devant étre chauffé au préalable et l’ceuf
jeté dedans. Inutile d’ajouter que le plat n’était absolument pas
présentable, ce qui, d’ailleurs, ne parut pas émouvoir outre
mesure notre malade. Ici encore il est bien évident qu'il ne
sagissait pas d’un trouble du langage, mais d’une déchéance
intellectuelle.”

Further, Marie denies that aphasics are able to express their
meaning, in the absence of speech, by means of descriptive mimicry.
For example, he states that he has never yet come across a patient
who was able in this way to indicate his occupation when asked
to do so.

He thus considers aphasia to be essentially characterised by
an impairment of the intellectual powers, and he therefore regards
the “area of Wernicke” as an intellectual and not a sensory |
centre. His views are consequently in accord with the more ‘
recent results of the study of cortical localisation, for the area of .
Wernicke is a zone of association and not an area of projection. ;
The visual and auditory word-centres naturally lie in either the
“sensory” or the “ psychic ” zones devoted to vision and hearing
respectively, for there is no essential difference between the cortical
projection of, and the conservation of the image of, a word, and
of any other cause of sensorial stimulation. Marie, in fact, though
he attributes word-deafness to defective comprehension and denies
the existence of this as a pure symptom, admits the existence of
word-blindness as a fairly pure symptom, associates it with hemia-
nopsia, and locates its lesion in the general visual centres. In
this connection the attention of the reader may be usefully drawn
to the observations already made on the psycho-physiology of
' the language mechanism in educated and uneducated persons.
Language is learned through the sense of hearing, and it is only
by education that it is further learned by the sense of sight. Word

j «

ON THE FUNCTIONS OF THE CEREBRUM = 335

vision is thus an additional acquisition superadded to the mechanism
of language, which under normal circumstances can carry on its
functions in the absence of the capacity to read and write. It is
therefore only to be expected that word-blindness should be found.
clinically to be fairly common as a pure symptom, and should be
less intimately associated with the general functions of the cerebrum
than word-deafness, which disability necessarily seriously maims
the normal, and earliest developed, mechanism for the acquisition
and reproduction of articulate speech.

It may be added that Marie does not .deny the existence of
pure motor aphasia, but he terms this “ anarthria,” and locates
_ its lesion in the lenticular zone, namely, “in the lenticular nucleus,
in its neighbourhood, in the anterior part and the genu of the
internal capsule, or, may be, in the external capsule.” That such
a lesion may cause the subcortical motor aphasia of Déjérine is
of course generally recognised, but Marie goes further and denies
that pure motor aphasia can also occur in consequence of a lesion
in Broca’s gyrus.

It is impossible to summarise here the pathological evidence
which is produced by Marie in support of his contention, but the
general scope of his inquiry may be indicated.

He states that an examination of the original specimens of
Broca clearly shows that they do not afford adequate support to
his localisation of the speech-centre in the posterior portion of
the third frontal gyrus. He remarks that when Broca enunciated
his doctrine in 1861 he was thirty-seven years of age, and was not
yet a professor; and that Bouillaud was sixty-nine years of age,
and had been professor of clinical medicine at la Charité for thirty
years. He then suggests that Broca’s views gained acceptance
owing to the still dominant influence of Bouillaud, who even in
1825 had localised the faculty of articulate speech in the frontal
lobes, which localisation Bouillaud regarded as confirmatory in
this respect of the phrenological doctrines of Gall. Marie then
traces the crystallisation of Broca’s views into the form of a dogma
to the experimental investigations of Fritsch and Hitzig, of Ferrier
and Yeo, &c.

With regard to his own researches, Marie states that his doctrine
of aphasia is based on the systematic examination, during a period
of ten years, of nearly a hundred cases of aphasia, which included
more than fifty autopsies.

336 RESEARCHES ON CORTICAL LOCALISATION AND

He adopts a twofold line of argument to prove that “la
troisiéme circonvolution frontale gauche ne joue aucun réle spécial —
dans la fonction du langage ” (p. 243). On the one hand he shows
that cases exist, in right-handed individuals, in which local de-
struction of the posterior part of the third frontal convolution is
not followed by aphasia. One of Marie’s figures in illustration
of such a case is reproduced opposite (Fig. 7).

On the other hand he shows that characteristic examples of
the aphasia of Broca occur in which the third left frontal convolu-
tion is absolutely intact. In Fig. 8 is reproduced an illustration
of such a case.

The patient was a beautiful example of the aphasia of Broca.
The gyrus of Broca is intact. The “aphasia of Broca” which
was presented by the patient is here attributed to a lesion R-R1,
which is the cause of the anarthria, and to a lesion R1-R11, which
has given rise to the aphasia.

The views of Marie, which in his first paper were indicated and
illustrated, rather than supported by the complete evidence on
which they are based, have naturally re-aroused interest in a
subject which of late years has been taught in dogmatic form
rather than investigated. One of his earliest critics was Déjérine,
who bitterly opposed his doctrines with regard to both sensory and
motor aphasia, and endeavoured to demonstrate that they are in
complete opposition to the facts derived from clinical observation.
Marie, in a subsequent article, replied in a masterly and restrained
manner to the vehement criticisms of Déjérine, and, in a third,
published an essay on the genesis and mode of evolution of the
doctrine of Broca.

In September 1907 an important discussion took place at the
International Congress at Amsterdam, and many of the leading
neurologists in the world expressed their views on aphasia. It
is a significant fact that the speakers as a whole appeared to lay
stress on the absence of definite knowledge regarding the exact
lesions which produce the different types of symptomatology
grouped under the term “aphasia,” rather than to discuss any
particular types of lesion.

The chief evidence on which the views of Marie are based has
recently been published by his pupil Moutier in a bulky volume
entitled L’Aphasie de Broca. In this work the whole question
of aphasia is elaborately and fully discussed. After a historical

.
|
;

-o—

Fic. 7. Fic. 8.

Fic. 7 (Marie, 1906).—Horizontal section of the left Paar aaeg of Ber...
The third frontal convolution is almost entirely destroyed by a softening. This
patient showed neither any sign of Aphasia nor any anarthric trouble.

Fic. 8 (Marie, 1906).—Horizontal section of the left hemisphere of Per. . . .

The softening met with here is the type of deep softening of form B. It is
indicated by the black line which, from R to R’, occupies the external capsule and
the base of the white substance of the convolutions of the insula. At R’ the
line of softening bifurcates and extends forward and inward towards the internal
capsule ; posteriorly the softening crosses the temporo-parietal isthmus, and passes
into the white substance of the temporo-occipital lobe R”, where it occupies the
neighbourhood of the external wall of the oe horn of the lateral ventricle, and
follows its contour closely ; it leaves this wall quite at the back of it and ends in
the white substance of the occipital lobe.

This patient was one of the finest cases of the Aphasia of Broca that I have had
the opportunity of observing. Here the Aphasia of Broca ‘had been set up, owing
to the ‘oles R R’ which had caused Anarthria, and to the lesion R’ R” which had
caused Aphasia,

na

7.

338 RESEARCHES ON CORTICAL LOCALISATION AND

description of the genesis and mode of evolution of the doctrine
of Broca, the following table (p. 96) is introduced—

RELEVE TOTAL DES CAS AVEC AUTOPSIE (1861-1906) . : . 804
Observations inutilisables . ‘ : : : : . ‘ . 201
1. Insuffisantes . : : : : : ; : . 26
2. Lésions trop étendues_ . ‘ ; , , ; . 175

RESTENT 103 OBSERVATIONS AVEC DESTRUCTION LOCALISKE :

1, Favorables a la 3° frontale (ou tenues pour telles) ‘ : . 19
(a) Lésion corticale : ‘ : . ; ' ; we
(b) Lésion sous-corticale . ; : : : , ramp &

2. Contraires a la 3¢frontale . , : : ; . 84
(A) Il y aaphasie. Le pied de F3 eat intact : : . 57

(B) Il n’y a pas d’aphasie. Le pied de F3 est détruit . 27
(a) Par traumatisme ; ; : ; 4
(6) Partumeur . : : : , ; . (14
(c) Par ramollissement. : : ‘ ; P 5
(ad) Des deux cétés : 2
(e) Chirurgicalement chez un droitier : 2

In this table the author summarises all the cases, recorded
up to 1906, in which the results of post-mortem examination are
stated. It will be noted by the reader that, of the 304 recorded
cases, but 103 possess the necessary details or exhibit sufficiently
circumscribed lesions, for their utilisation as evidence for or against
the doctrine of Broca. Of these 103 cases but 19 are in favour
of, and no less than 84 are against, the localisation of the speech-
centre in the posterior part of the third frontal convolution.

The subject of aphasia is considered in detail from both
anatomical and clinical aspects. A complete bibliography from
1861 to 1907 is inserted. According to their relative importance,
more or less lengthy details regarding the cases recorded in the
several publications are inserted in a convenient form for reference.
Half the volume is devoted to a description of the personal obser-

‘vations of the author. The methods employed for the clinical
examination of aphasics are described, and detailed records of
44 cases are inserted. The book contains 175 illustrations, many
of which are full-page plates.

The bearing of the views of Marie on the subject of cortical
localisation will now be considered.

It must at once be confessed that the doctrines of Marie are
destructive rather than constructive from the aspect of cortical

————— rl

- ON THE FUNCTIONS OF THE CEREBRUM — 339

localisation. On the other hand, from the aspect of cerebral
function, they are throughout constructive in tendency. From
both points of view, however, they are in accord with the results

of recent histological and psycho-physiological research.

From the aspect of cortical localisation, Broca’s speech-centre
is disrated by Marie. This is a conclusion for which modern
histological investigations have already prepared the way. On
referring to the maps of Brodmann and of Campbell, the reader
will see that both these observers indicate a histological type
of cortex (“intermediate precentral” of Campbell, and 44 of
Brodmann) in the posterior third of the inferior frontal con-
volution, which differs from that of the psychomotor area.
Campbell, in fact, whose monograph appeared before the publi-
cation of the papers of Marie, protested against the assumption
that a lesion of the area of Broca is the essential factor in the
production of motor aphasia on the ground that this region is
histologically undifferentiable from, and is included in, his “ inter-
mediate precentral” area. He cites two cases of destruction of
Broca’s area in which permanent motor aphasia existed. In a
third case, however, in which the area of destruction is even
more extensive, the patient, though twelve years previously he had
suffered from complete but transitory aphasia, exhibited no speech
defect whatever during the whole of this period and right up to
the time of his death.

The more detailed map of Brodmann, it is true, indicates a
special histological type (No. 44) in Broca’s area, but this type
does not possess “ motor” characteristics, and is indeed separated
from the psychomotor or Betz-cell region (No. 4) by an area (No. 6)
which, though less in extent, is similar in distribution to the “ inter-
mediate precentral” area of Campbell. If, as Campbell suggests,
this last area is “ specially designed for the control of skilled move-
ments of an associated kind,” his argument re motor aphasia is
strengthened by the exclusion from this “ intermediate precentral ”
region, by Brodmann, of Broca’s atea.

The views of Marie will now be considered with regard to. their
bearing on our knowledge of the functions of the cerebrum. Marie
states that the essential feature of aphasia is the existence of
intellectual impairment, although the patient may appear, from
the aspect of every-day life, to possess normal mental faculties.
To put this opinion into other words, Marie in effect states that

340 RESEARCHES ON CORTICAL LOCALISATION AND

the sufferer from aphasia is sane, but at the same time suffers
from intellectual disability.

As bas been remarked earlier in this article, the prefrontal _
region (No. 10 of Brodmann) is the highest zone of association,
and insanity depends on sub-evolution or dissolution of this region.
In the case of sub-evolution the patient may be permanently
idiotic or imbecile, permanently or temporarily insane, or liable
to the ‘onset of insanity: in the case of dissolution, according
to its degree, the patient suffers from a corresponding grade of
permanent dementia.

On the other hand, it has been stated that the post- and infra-
Rolandic regions of the cerebrum contain the sensory projection
spheres and the various zones of association subserving the
complex associational processes which occur with regard to the |
projection spheres individually and collectively. A gross lesion
situated in the “area of Wernicke,” 7.e. in the very midst of this
region of association, must therefore seriously interfere with the
performance of the cerebral functions of lower association, namely,
with the evolution of percepts of various types and grades of
complexity.

Further, according to the distribution and depth of the lesion
almost any grade and type of psycho-sensorial disability may be
expected. The greater its proximity to the visual or auditory
projection spheres, the greater must be the likelihood of relatively
pure word blindness or deafness. For reasons already stated,
the former of these disabilities can only occur in persons who
have learned to read and write, and it is the more likely to exist
in a pure form. The latter can occur in either educated or un-
educated individuals, and in either case is unlikely to exist in a
pure form (see pp. 334-5).

On the other hand, a lesion, and especially a superficial one,
located away from the projection spheres, would be expected to
cause disabilities with regard to the more complicated processes
of lower association, with resulting intellectual impairment.

As will have been gathered from the remarks on the function
of language, the complex mechanism which serves as its physical
basis must necessarily be co-extensive in distribution with the
projection spheres, and the whole region of lower assocviation.
The visual and auditory word-centres lie in or near the visual and
‘auditory projection spheres, as words seen and heard are merely

)
‘

ON THE FUNCTIONS OF THE CEREBRUM 341

one variety of sensorial impression. On the other hand, the more
or less complex cerebral processes which are needed for the evolu-
tion of the percept symbolised by a certain word may involve the

cortex in and near each of the several projection spheres. For

example, the word “ mouse” at once sets on foot processes of
association which pass to every projection sphere with the solitary
exception of the gustatory, and even this may be reached in a
person who has eaten a fried mouse in the hope of thereby re-
covering from an attack of whooping cough.

We may note a word, i.e. receive the sensorial impression
produced by it; we may go a step further and recognise it as
understandable ; but it is only when, by active, though not
necessarily voluntary, processes of cerebral association, numerous
sensori-memorial images of different orders have thereby been
aroused into the field of consciousness, that the word acquires
meaning. These processes of association are of widespread dis-
tribution, and differ in detail, though they are similar in their
general tendency, on each occasion on which they occur. In the
normal brain these processes of association are directed and con-
trolled, and suitable sensori-memorial neurone complexes are ac-
cepted, whilst undesirable are rejected, by means of the centre of
higher association. In dreamy states they follow certain natural
laws, and their course depends solely on the existing state, as
regards excitability, of the various associated groups of neurones.
In the maimed brain of an aphasic, whether it be functioning
in a controlled or in an involuntary manner, such processes
of association are necessarily imperfectly and inadequately
performed.

The fairly common, rather than very occasional, determination
of an “area of Wernicke,” and therefore of “ aphasia ” as a special
symptomatology, like the determination of other special symp-
tomatologies through local cerebral lesions, depends, in fact, on
the distribution, and consequent liability to occlusion, of certain
branches of the cerebral arteries. Had the arterial supply of the
cerebrum been evolved in a different manner, it is conceivable
that “aphasia,” as it occurs, would be unknown, for lesions due,
eg. to tumours, traumatism, &c., would not have sufficed for its
complete identification and description.

“ Aphasia,” however, exists, as a complex of varying types of
symptomatology ; and the study of these by Marie has produced

342 RESEARCHES ON CORTICAL LOCALISATION AND

a mass of evidence which confirms the correctness of the obser-
vations with regard to cortical localisation and cerebral function
which have been recorded during recent years. These observations
are difficult to correlate with—in fact, they are in many respects
opposed to—the hitherto current doctrines with regard to aphasia ;
but they have received confirmation and derived illumination from
the researches of Marie.

The attention of the reader will finally be drawn to certain
matters of interest with regard to the functions of the cerebrum,
and to a number of recent publications, the consideration of which
could not be conveniently introduced into the general text of this
article without interference with its continuity.

The first subject which will be briefly indicated is termed
“alteration of personality.” This may be conveniently defined
as a mental state in which the higher cerebral functions are
exercised, not over psychic processes founded on such recently
acquired time-related portions of the content of mind as con-
stitute the normal personality, but over psychic processes founded
on complex and time-related portions of the subconscious content
of mind, which exhibit such abnormal prominence as to entirely
replace for the time those recent experiences on which normal
cerebral activity depends. In such cases not only one, but several
such time-related portions of former experience, may separately
and at different times acquire abnormal prominence, and thereby
give rise to the phenomena of multiple personality. In the normal
individual, on the other hand, the recent time-related personality
cannot be voluntarily subordinated, and all that is possible in this
direction is the occurrence of some degree of associational elabora-
tion of former sensori-memorial images, which is always imperfect
and often incorrect. To test the truth of this statement, the
reader needs only to endeavour to recall, in a time-related manner,
the events of yesterday.

This “alteration of personality” or switching on of a former
period of cerebral activity, with temporary obliteration of later
experience, is common in hysteria, epilepsy, and hypnotic states.
The phenomenon is of importance in that it proves that, whilst
the exercise of the cerebral functions is an active process which
derives its pabulum from both the past and the present, the whole
of the psychic life is nevertheless recorded in the cerebrum in a@

ON THE FUNCTIONS OF THE CEREBRUM 343

time-related manner. Thus, in certain pathological states of the
cerebrum, not only may the clock of cerebral activity be put
back, but the subject may reproduce in exact detail lengthy
portions of former experience, and, stranger still, may start an
entirely new time-related psychic life from the point of former
experience to which he has returned. He may then, as if nothing
had happened, return to the normal point of cerebral activity
and recommence his ordinary time-related psychic life, with com-
plete obliteration, as far as his conscious knowledge is concerned,
of the experiences he has passed through whilst in the abnormal
psychic state. It is possible, then, for a person to live two or
more psychic lives, of which only one is normal, and in his normal
waking state to be entirely unaware of the existence, apart from
periods of time for which he cannot account, of his other, or
numerous, “sub-egos.” Interesting cases of “ multiple person-
ality ” which might seem incredible had they not been studied and
recorded by competent and entirely trustworthy observers, have
recently been published by Morton Prince and by Albert Wilson.
Three less important cases have also been published by Lemaitre.
Such cases differ somewhat from good examples of systematised
delusional insanity, which are, however, of interest in this con-
nection. In the latter the personality is altered, but this altera-
tion is due, in the developed state, to the permanently abnormal
prominence of certain time-related portions of what should be
part of the subconscious content of mind. These particular time-
related experiences serve as a basis on which develops a continually
increasing aggregation of abnormal psychic units. In other words,
in place of the normal gradually changing personality, a certain
former personality remains as a permanent basis on which is built
up a continually increasing abnormal psychic edifice. In such
cases, when they become “ chronic,” it is probable that the greater
part of the available psychic content consists of symbolic verbal
groupings which have become relatively stable through frequent
repetition ; and that the processes of cerebral association required
for the reintegration of the former percepts and concepts which
these verbal groupings symbolise, and for the revival of old sensori-
memorial images, are markedly reduced. These symbolic verbal
groupings continue throughout the life of the sufferer to entirely
dominate what would otherwise be relatively normal processes of
immediate cerebral activity, and in this, in effect though greater

f
:

344 RESEARCHES ON CORTICAL LOCALISATION AND

in degree, resemble the “opinions” of many of the one-idea-ed
“cranks” in the outside world.

It may be remarked that these various abnormal types of
cerebral activity are at present chiefly of academic interest, apart
from their obvious bearing on criminology. Our knowledge of the
psycho-physiology of the brain is still in its infancy, and though
it 4s at any rate certain that in such cases the cerebrum is not
functioning in a normal manner during the phases of “ alteration
of personality,” not only is no satisfactory explanation yet forth-
coming, but it is even difficult to be certain in the complicated
cases which of the several phases represents the “normal.” It
is probable, however, that the subject will receive illumination
when our present crude acquaintance with mental disease is
replaced by the scientific knowledge which will undoubtedly
follow its systematic study.

Though the more difficult question of the time-related recording
of psychic experience in the cerebrum, and of the influence of this
on the normal processes of cerebral association, is at present an
obscure one, the simpler problem of the manner in which the
immediate functions of the cerebrum are performed derives much
illumination from the study of insanity. It would be an un-
warrantable digression to discuss here the various abnormal
types of immediate cerebral activity which are met with during
the clinical investigation of mental disease. One or two examples
may, however, with advantage be introduced for illustrative
purposes.

In certain cases classed under the symptomatological group
of “ mania,” the centre of higher association is in functional abey-
ance, and the cerebrum acts as an uncontrolled sensori-psycho-
motor machine. Instead of, as normally happens, but a small
selected number of the ever-entering stream of afferent impres-
sions being noticed, almost every visual and auditory stimulus in
the neighbourhood of the patient is accepted. Processes of cerebral
association incited\by these occur pell-mell, and find motor ex-
pression in emotional disturbance, rapid movements, and a riotous
display of words. It is impossible to obtain more than the
momentary attention of the sufferer. This condition of uncon-
- trolled sensori-psychomotor activity may last for many weeks,
after which the patient becomes, at any rate for the time, sane.
Such patients usually exhibit numerous signs of physical and

e

ON THE FUNCTIONS OF THE CEREBRUM = 345

mental degeneracy ; but all grades exist, from individuals who
may be regarded, in their normal condition, as “ sane,” to others,
of greater cerebral degeneracy, who are never really so. In such
cases the cerebrum, as regards its lower complexes, is “ racing ” ;
and, in the more degenerate types, objective signs of generally
aberrent and sub-normal cerebral activity are permanently in
evidence.

On the other hand, cases are common in which, from toxemia
of the cortical neurones and consequent pathological conditions of
these elements, all grades and types of temporary or permanent
maiming of the processes of cerebral association are existent.
Such patients exhibit what is described as ‘‘ mental confusion.”
The earliest evolved and most stable parts, 7.e. the projection
spheres, are the least affected, and hence the patients are able
to receive sensory impressions in a more or less normal manner.
The later evolved zones of lower association (and especially the
latest evolved centre of higher association) are, however, more
seriously affected, and hence the patients make frequent mistakes
with regard to the identifying of sensations, suffer from halluci-
nations, and may exhibit any type and grade of defective com-
prehension and any symptom of “aphasia.” In such cases the
cerebrum is temporarily or permanently maimed owing to lesion
of its constituent elements. __

Though examples of abnormal cerebral activity of the immediate
type might be multiplied to any extent, those given above will
suffice to indicate that our knowledge of the higher functions of
the cerebrum, though still in its early stages, does not depend
solely on histological, neuro-pathological, and experimental data,
but may derive illumination and illustration from the study of
mental disease.

A number of recent papers of interest will now be referred to.

The mechanism and localisation of the psychic processes has
formed the subject of a recent paper by Jendrassik. This writer
denies the existence of an “ association centre,” on the ground that
the connections between memory images are not actual paths but
occur through a “‘ tuning” of associated images, with the result that
if one of these is evoked the images in harmony with it are also aroused
into consciousness. His theoretical discussion is rather unsatisfactory,
but the deduction may be readily drawn that he considers association
_ to be a process, and the psychic products, which are evolved as results

346 RESEARCHES ON CORTICAL LOCALISATION AND

of this, to have no fixed cerebral centres. His opinion thus approxi-
mates to the views enunciated during the course of this article.

Bianchi, on the other hand, considers that the cerebrum, apart
from the frontal lobes, is the seat of centres for percepts, and that a
centre for concepts exists in the prefrontal region. He argues that
both percepts and concepts exist apart from words, though the evidence
he adduces is chiefly or entirely in favour of the existence of words
in the absence of percepts and concepts. He severely criticises the
doctrine of Flechsig, chiefly on the ground that the phenomena of »
anatomical evolution do not correspond with those of the development —
of functional activity. For example, he remarks that the supposed
centre for reading in an imbecile may be completely myelinated although
the subject may never have learned to read. He states that histo-
logical evidence is not in favour of the areas of projection possessing
a simpler structure than the regions of association. He discusses the-
complex nature of the processes of association which are necessary
for the synthesis of a perception. He thus regards the portion of the
cortex which is now differentiated into areas of projection or sensory
areas and into posterior regions of association, as a series of perceptive
zones ; and he is of the opinion that the only regions of the brain
which can be regarded as associational are the prefrontal lobes, which
are generally admitted to contain no projection fibres. He regards
these lobes as the region of cerebral executive government, and con-
siders that here the elaborated products of the perceptive zones, or
mantellar parliament, are fused together.

Instead of three anatomical grades in the hierarchy of cerebral
function, namely, areas of projection, regions of lower association,
and a region of higher association, Bianchi thus recognises but two,
zones of perception and a centre for concepts.. Further, he regards
percepts and concepts as entities with an anatomical basis apart from
that for words. His opinion thus differs from the views elaborated
during the course »f this article, namely, that percepts and concepts
are merely psychc'ogical generalisations signifying the results of
‘processes of cerebrai association which differ in detail, though they
possess an underlying gen¢ral similarity, on each occasion on which
they occur. Bianchi regards words, not as symbols for the integration
of processes of cerebral axsociation without which they are meaningless,
but as means for the communication of already existing percepts and
concepts. Language, in the opinion of Bianchi, is thus merely a
mechanism for the expression of thought, and not, as is the view of —
the writer, a symbolic instrument without which it is impossible for
the psychic functions to be adequately performed.

|

ON THE FUNCTIONS OF THE CEREBRUM 347

Mills and Weisenburg have published a paper in which, after col-
lating the clinical evidence in favour of the localisation of the higher
psychic functions in the prefrontal lobe, they describe an interesting
case of left prefrontal tumour. The patient, a physician, was affected
with regard to his higher psychic functions, his judgment and powers
of comparison, his grasp of work, his disposition, &c.

Shepherd Ivory Franz has published a series of observations on
the effect of experimental lesions of the frontal lobes in monkeys and

cats. He finds that when these lobes are destroyed recently formed

habits are lost ; and he indicates his reasons for concluding that the
results are not due to shock. Unilateral lesions. are followed merely
by a slowing of motor impulses. He concludes that the frontal lobes

appear to be concerned in the performance of normal and daily associa-

tional processes, and that by means of them we are able to learn and
to form habits. R

Mills and Weisenburg have recently produced clinical and patho-
logical evidence indicating that the cortical areas for the representa-
tion of movements, of sensibility, and of stereognosis are distinct from
one another and are each divided into several sub-areas.

Oskar Vogt has published an interesting article on the functional
significance of the pre- and post-central gyri. He confirms from the
experimental aspect the researches of Sherrington and Griinbaum with
regard to the pre-Rolandic position of the excitable motor areas. He
shows that the anterior limits of the excitable limb areas correspond
accurately to those of Brodmann’s pre-central type (No. 4); and that
the centres for movements of the head and eyes and for mastication
correspond with the still more anterior histologically differentiated
area of Brodmann (No. 6). In certain of the lower apes he has found
that the excitable region does not extend as far back as the fissure
of Rolando, and that the motor type of cortex in these has the same
posterior limits. Further, by a study of the ‘effects of destructive
lesions in eleven lower apes, he concludes that palsy without ataxy

- follows destruction of the pre-central gyrus, and that considerable

ataxy but no palsy results from destruction of the post-central

Eugen Wehrli, in a paper dealing with lesions of the occipital
region, denies that these afford proof of the exact cortical localisation
of the visual area; and he is not disposed to regard local differences
of histological structure as evidence in favour of the localisation of’
the visual area in a special region of the cortex. This paper well
illustrates the critical attitude still held by many writers with regard
to the recent researches on cortical localisation, and indicates. that

348 RESEARCHES ON CORTICAL LOCALISATION AND

the most elaborately detailed investigations, even when repeatedly
confirmed, may still fail to gain general acceptance.

The last investigation which will be referred to is not of direct
physiological interest, but is nevertheless worthy of mention owing
to its bearing on the subject of heredity. J. P. Karplus has recently
published a work which deals with the fissuration of the human cere-
brum from the aspect of family likeness. He has examined in a series
of cases the cerebra of two or more members of a family, and also the
brains of several members of families in the ape, dog, rat, and goat.

He draws interesting conclusions with regard to the family likeness
of the pattern of the fissures. He further finds that, whilst in the
monkey the two hemispheres resemble one another, in man the original
bilateral symmetry of fissuration is lost, and the sulci of the individual
hemispheres possess a family permanence.

Whilst it is true that the convolutional pattern of the brain does-
not run hand in hand with, and in fact bears little relationship to,
the various histologically differentiated areas into which the cerebral
cortex has been divided, the truth that the former is susceptible to
the impress of heredity is at least suggestive with regard to the possi-
bility of this in the case of the latter.

BIBLIOGRAPHY

L. Bianchi, On the Teaching of Flechsig with regard to the Perceptive
and the Associative Zones. Internat. Med. Congress of Madrid, 1903. Text-
book of Psychiatry, translated by J. H. Macdonald, 1906.

J. S. Bolton, The exact Histological Localisation of the Visual Area of
the Human Cerebral Cortex. Phil. Trans., vol. 193, 1900. The Histological
Basis of Amentia and Dementia. Archives of Neurol., vol. ii., 1903. The
Functions of the Frontal Lobes. Brain, 1903. Amentia and Dementia: a
Clinico-Pathological Study. Journ. Ment. Sci., 1905-8, chiefly April 1905,
April 1906, and April and July 1908.

K. Brodmann, Beitrage zur histologischen Lokalisation der Grosshirnrinde,
‘Journ, fiir Psychol. und Neurol. Mitteilung I. Die Regio Rolandica. Bd. 2,
1902-3. Mitteilung II. Der Calcarinatypus. Bd. 2, 1903. Mitteilung IIT.
Die Rindenfelder der niedéren Affen. Bd. 4, 1905. Mitteilung IV. Der
Riesenpyramidentypus und sein Verhalten zu den Furchen bei den Karni-
voren. Bd. 4, 1905. Mitteilung V. Uber den allgemeinen Bauplan des
Cortex pallii bei den Mammaliern und zwei homologe Rindenfelder im
besonderen. Zugleich ein Beitrag zur Furchenlehre. Bd. 6, 1906. Mit-
teilung VI. Die Cortex gliederung des Menschen. Bd. 10, 1907,

A. W. Campbell, Histological Studies on the Localisation of Cerebral
Function. Cambridge, 1905.

ON THE FUNCTIONS OF THE CEREBRUM 349

J. Dé&erine, Liaphasie sensorielle. Sa localisation et sa physiologie patho-
logique. La Presse médicale, 11 Juillet 1906. L’aphasie motrice. Sa
localisation et sa physiologie pathologique. La Presse médicale, 18 Juillet
1906.

L. Edinger und A. Wallenberg, Bericht ueber die Leistungen auf dem
gebiete der anatomie des centralnervensystems. Dritter Bericht, 1905 und
1906.

S. I. Franz, On the Functions of .the Cerebrum. The Frontal Lobes.
Arch. of Psychology, March 1907.

W. Harris, Binocular and Stereoscopic Vision in Man and other Verte-
brates with regard to Decussation of Optic Nerves, Ocular Movements and
Pupil Light Reflex. Brain, cv., 1904.

Hermanides und Képpen, Uber die Furchen und iiber den Bau der Gross-
hirnrinde bei den Lissencephalen, insbesondere iiber die Lokalisation des
motorischen Zentrums und der Sehregion. Arch. f. Psychiatr., 37, 1903.

Gordon Holmes, A Note on the Condition of the Post-Central Cortex in
Tabes Dorsalis. Rev. of Neurol. and Psychiat., vol. vi., No. 1, 1908.

Ernst Jendrassik, The Mechanism and Localisation of the Psychical
Processes. Neurol. Centralb., xxvi., 1907, pp. 194 and 254,

J.P. Karplus, Zur Kenntnis der variabilitat und vererbung am zentral-
nervensystem des menschen und einiger siugetiere. Wien, 1907.

W. Kolmer, Beitrag zur Kenntniss der “ motorischen” Hirnrindregion,
Arch. f. mikr. Anat. u. Entwgesch., 57, 1901.

Koppen und Lowenstein, Studien iiber den Zellenbau der Grosshirnrinde bei
den Ungulaten und Karnivoren und iiber die Bedeutung einiger Furchen.
Monatsch. f. Psychiat. u. Neurolog., 18, 1905.

A, Lemaitre, Trois cas de dissociation mentale. Arch, de Psychol., 1907,
p- 252.

Bevan Lewis and Henry Clarke, The Cortical Localisation of the Motor
Area of the Brain. Proc. Roy. Soc., No. 185, 1878.

Pierre Marie, Revision de la question de l’aphasie. La Semaine médicale,
1906, 23 Mai, 17 Octobre, and 28 Novembre.

Millis and Weisenburg, Localisation of the Higher Psychic Functions.
Journ, Am, Med. Assoc., Feb. 1906. The Subdivision of the Representation
of Cutaneous and Muscular Sensibility and of Stereognosis in the Cerebral
Cortex. Journ. of Nerv. and Ment. Dis., Oct. 1906, p. 617.

F. D. Mitchell, Mathematical Prodigies. Am. Journ. of Psychol., Jan.
1907.

Von Monakow, Aphasia and Diaschisis. Neurol, Centralb., Noy. 16, 1906,

1026. .
ha F. W. Mott, The Progressive Evolution of the Structure and Functions

of the Visual Cortex in Mammalia. (Bowman Lecture, 1904.) Arch. of
Neurol., vol. iii., 1907.

Mott and Halliburton, Localisation of Function in the Lemur’s Brain.
Proc. Roy. Soc., 1907, B. vol. 80, p. 136.

Mott and Kelley, Complete Survey of the Cell Lamination of the Cerebral
Cortex of the Lemur. Proc. Roy. Soc., 1908, B. vol, 80, p. 488.

F. Moutier, L’aphasie de Broca, Paris, 1908.

~~

350 RESEARCHES ON CORTICAL LOCALISATION

Morton Prince, The Dissociation of a Personality : a Biographical Study
in Abnormal Psychology. New York, London, and Bombay, 1906.

Eleanor H. Rowland, The Psychological Experiences connected with the
different Parts of Speech. The Psychological Seige Monograph Supple-
ment, January 1907.

Elliott Smith, The Morphology of the Occipital Region of the Cerebral
Hemispheres in Man and the Apes. Anat. Anz., 24,1904. Studies in the
Morphology of the Human Brain, with Special Reference to the Egyptians,
No. 1, The Occipital Region. Records of the Egyptian Gov. School of Med,
2, 1904. A New Topographical Survey of the Human Cerebral Cortex,
Journ. of Anat. and Phys., 41, 1907.

John Turner, A Study of the Minute Structure of the Olfactory Lobe and
Cornu Ammonis. Brain, 1906, p. 57. The Structure of Grey Matter. Brain,
1907, p. 426.

0. Vogt, Uber strukturelle Hirncentra, mit besonderer Beriicksichtigung
der strukturellen Felder des Cortex pallii. Verhandl. der anatom. Gesellsch.,
1906, p. 74. Der Wert der myelogenetischen Felder der Grosshirnrinde.
Anat. Anz., 29, 1906.

G, A. Watson, The Mammalian Cerebral Cortex, with Special Reference
to its Comparative Histology. I. Order Insectivora. Arch. of Neurology,
vol, iii., 1907. «

E. Wehrli, Ueber die anatomisch-histologische Grundlage der sog.
Rindenblindheit und ueber die Lokalisation der corticalen Seesphere der
Macula lutea und die Projection der Retina auf die Rinde des Occipital-
Jappens. V. Graefe’s Archiv., lxii., 2, 1906.

Albert Wilson, Education, Personality, and Crime. London, 1908.

~~ ——__

STUDIES IN SPECIAL SENSE PHYSIOLOGY
By M. GREENWOOD, Juwr.

PART I.—VISUAL ADAPTATION

Ir one asked a number of students, taken at random, which de-
partment of physiology seemed to them the least interesting, I
am confident that a majority would award the palm of dulness
to that subdivision which treats of the special sense mechanisms.

It is, indeed, not difficult to understand such a result. Our
knowledge of special sense physiology is at once very complete and
very incomplete ; observations and experiments have accumulated
to an enormous extent, yet we are far from the synthesis of these
results which makes the inter-relationship of the various parts
clear and enables the intelligent reader to perceive that the sub-
ject is an harmonious system, not a mere collection of disconnected
fragments.

I think, therefore, the reader will more easily appreciate the
scope and method of this branch of science if I choose two
problems only, and examine them in detail, not so much because
they are of practical importance, but as illustrations of the lines —
upon which modern thought and experimental work seem to
advance. :

In the present section, I shall sketch the course of recent in-

_ quiries into the phenomena of adaptation of the eye to various

intensities of light, a subject which illustrates the practical methods
of work ; in the later section I shall attempt to set out the principles
of two modern theories of colour vision, and to show how far they
may be regarded as really new contributions to science, and to
what extent they are products of thought handed down to us from
remote ages. Here, as in so much of modern science, we shall
find that old and new are inextricably interwoven, that much of
what is taken to be modern is so only in a geological sense.

It has long been known that the nature of the response by the

86

Bs
352 _ STUDIES IN SPECIAL SENSE PHYSIOLOGY

eye to a stimulus largely depends upon whether, before the ex-
periment, the subjects have rested in a dark room or been exposed
to light—that is to say, whether there be a condition of light or
dark adaptation.

Many years ago, Aubert noticed that the response of the eye
to feeble stimulation was increased by resting in the dark, and also
laid down the rule that the threshold value of a stimulus in such
cases varied inversely as the area of surface stimulated. This
general statement received ample confirmation ; Charpentier (1),
for instance, found that the central part of the ‘“‘ dark”? retina,
although exhibiting an increased response as compared with the
same region in the “light” eye, was far less sensitive than the
periphery. This increased responsiveness was very marked in
respect of the short waved regions of the spectrum, indeed it .
is denied by many good observers that adaptation affects the
response to red light at all (Parinaud and v. Kries), while nobody
has demonstrated a large increase. |

Of the many who have studied the changes of responsiveness
in adaptation, all agree that they are far more prominent in the
peripheral than in the central region, but much dispute has arisen =
as to whether any part is absolutely unaffected. On the whole, :
it may be said that no satisfactory proof is forthcoming that 7
such a part exists. Experimentally, the problem is beset with '
difficulties, for it is hard to be certain of the exact limits of a very
small stimulated field, and it is possible that the time required for
adaptation is not the same in the fovea and the peripheral regions,
being probably longer in the former (Tschermak °)..

These changes in responsiveness immediately lead us to the
consideration of Purkinje’s “ phenomenon,” an effect which may
be described in the following terms. If one examines an ordinary
spectrum, the brightest part of it seems to occupy the neighbour-
hood of the yellow or orange-yellow ; if now its physical intensity
be diminished—for instance, by moving the source of light farther
away from the prism or grating—the maximum of brightness is.
shifted towards the violet end. With the feeblest illumination
which enables us to detect the spectral colours at all, the brightest
part is at the junction of the green and blue.

Hering (*) by means of a simple experiment has made it seem —

1 For brevity, I shall speak of an eye which has been rested in darkness as a
‘dark ” and one previously exposed to light as a ‘‘ light” eye.

—— ——

——

STUDIES IN SPECIAL SENSE PHYSIOLOGY = 353

probable that these changes are due to adaptation. Two rooms
which could be independently darkened are separated by a light-
proof partition in which two slits are cut and covered with pig-
mented glass. The amount of light transmitted by these slits
can be varied independently with the aid of reflectors. So long as
the room occupied by the observer is kept at a constant illumina-
tion, diminishing the physical intensity of the light traversing the
two slits, which are covered with blue and red glass respectively,
does not change their relative intensities. If, however, the ob-
servation room is darkened, the blue slit immediately appears
brighter than the red one, even while the physical intensity of light

passing through them is unaltered. This effect is enhanced by a

prolonged stay in darkness, and is more noticeable in indirect
(peripheral) than direct (central or foveal) vision. Burch, in a
series of experiments which I shall discuss later, has obtained
similar results, so that we may conclude that Purkinje’s “ pheno-
menon” depends not on physical intensity but visual adaptation,
and is a particular case of the general change already mentioned.
These facts naturally incline us to examine more closely the
differences between peripheral and central vision, and we shall

’ find that all work tends to show that the former is more susceptible

to adaptive changes and characterised by a heightened responsive-
ness to feeble stimuli.

Before going further, however, we must ask ourselves what: is
meant by saying that different colours are equally or unequally
bright. As a matter of fact, this question is more easily asked
than answered. -A similar difficulty is experienced in attempting
to ascertain what one means by saying that two notes of different
pitch are unequally loud. If we attempt to define our meaning in
terms of the physical properties of exciting stimuli, we become

confused, and perhaps the only valid excuse for employing the

expression is an empirical one. Ask a dozen normal persons to
look at a spectrum in daylight, and they will agree that the yellow
is the brightest part of it, meaning, I suppose, that the region, in
question produces, somehow, a predominant effect in consciousness.
This uniformity of results is a justification, perhaps the only justi-
fication, of the method, and allows us to compare different colours
with respect to brightness.

Bearing in mind the empirical and sensational nature of the
investigation, we can attain comparative results in numerous ways.

; Z

354 STUDIES IN SPECIAL SENSE PHYSIOLOGY — |

One of the best is the “ flicker” method which has been carefully
studied in England by Haycraft (*) and Rivers (°). If a series of
sectors are whirled round on a colour mixer, the rapidity necessary
to produce a fused sensation depends upon the brightness of the
sectors; hence with different sets of sectors equal in size, the
velocity of rotation which just extinguishes the sensation of flicker
will afford us a measure of brightness, this varying, within certain
limits, inversely as the rapidity of rotation. Many other plans
can be, and have been, adopted, some of which will be mentioned
later. The above should give the reader some idea as to how
researches can be arranged.

Hering, in 1890, noted the relative darkening of red as one
passes from central to peripheral vision ; he compared a pure red,
a spectral mixture of red and blue green (656 wu+470 uu) and
daylight. The converse was found to hold for spectral green
(505 wu), but his results were not quite pure, since momentary
dark adaptation occurred during the experiments (*). ‘Tschermak (°),
who studied the whole question systematically in the “light ” eye,
found with indirect vision a relative diminution in brightness for
light of wave length between 693 and 525 wu, no change from
525 to 516 wu, an increase from 516 to 466 uu. Similar changes
were observable in “dark” eyes.

Another line of research was to start with a large field of colour-
less light, produced by mixing together complementaries, and then
to diminish its size. It has been found that a colourless mixture
of spectral red and bluish-green becomes, with such areal diminu-
tion, redder and darker; if the change of size be an increase, it
becomes greener and brighter. In fact, both for “light” and
“dark” eyes, colourless matches valid for the periphery do not
hold for the centrum and vice versa. Apart from adaptation, it
_is interesting to see whether merely changing the physical in-
tensities of the two mixtures renders the match invalid. It is
agreed that mere intensity variation does not affect central matches,
but there is much dispute as to the periphery. V. Kries and his
fellow-workers have \brought forward experimental evidence on
the affirmative side,\but difference of opinion exists. Thus,
v. Kries (7) found the equation R+G=/Y, no longer valid on
diminishing the intensities of both fields, the binary colour growing
paler and brighter. We\ must remember that it is extremely
difficult to avoid changes in the state of adaptation, and as these

\

STUDIES IN SPECIAL SENSE PHYSIOLOGY 355

are especially important at the periphery, it is probable that
some of the results have been vitiated by this circumstance
(Tschermak ?).

- In connection with the supposed relation between physical
intensity and apparent brightness, an interesting set of observa-
tions may be noted regarding what is called the “achromatic
threshold of coloured light.” In studying Purkinje’s “ phenomenon”
we found that if the intensity of a spectrum were steadily diminished,
a point was reached at which the brightest region appeared to have
been moved towards the violet. What, it may be asked, happens
if the illumination be still further diminished ? Under normal
circumstances we soon reach a point at which the whole spectrum
appears colourless, differing, however, in brightness in the various
regions. Reduction beyond this yields an intensity which is
associated with no sensation at all. Hence it seemed necessary
to distinguish between the absolute liminal intensity of a spectrum,’
that is, the least intensity corresponding to a colourless sensation,
and the “ specific ” threshold or liminal value for which the spectral
zones could be seen to differ in hue.

A good many workers, including Purkinje, Helmholtz, Aubert,
Landolt, &c., observed this phenomenon, and the actual absolute
threshold values for various spectral lights and different parts of
the retina have been studied. Charpentier (') found the “ photo-
chromatic interval” (i.e. the difference between specific and abso-
lute threshold intensities) least for red and greatest for blue light,
and that the absolute thresholds were diminished by dark adapta-
tion, while the specific liminal values were not affected. It also
appeared that these results were more noticeable with peripheral
than central vision.

It was soon noticed, however, that the phenomena were in
_ reality complex. Some workers (e.g. Parinaud and v. Kries)
never obtained an achromatic value for red, and doubts arose as
to the existence of such intervals at all. Finally, on comparing
the brightness of central and peripheral lights, rendered colourless
by a reduction of physical intensity, unexpected and puzzling
results were obtained. _

Stegmann (°) performed the following experiments. Matches
were made between a series of lights from 640 to 480 uu, and a

1 The liminal value or threshold value of a stimulus is that intensity which
corresponds to a “‘ just-noticeable ” sensation. ,

.
356 STUDIES IN SPECIAL SENSE PHYSIOLOGY "

screen of blue-green or orange paper, illuminated by lamp light
passing through an absorbing medium, the fixed illuminant being
so chosen that no colour was discernible. The tested lights were
arranged in the first series of experiments at an eccentricity of
twenty degrees; in the second, at one of four degrees. In the
first set of observations, Stegmann found that, after five to fifteen
minutes’ dark adaptation, a diminution of 21 to 45 per cent. in
orange intensity, and an increase of 23 to 50 per cent. in blue-green
intensity were necessary in order to match the fixed standard ;
that is to say, below the chromatic threshold, the peripheral
responsiveness was increased with respect to the long waved light
and diminished with regard to the short-waved light, 7.e. a change
the exact converse of that associated with the ordinary Purkinje
effect. V. Kries concluded that these results depended on the.
feeble intensity of the stimulus employed, and that with light
stronger but still below the chromatic threshold, the results agreed
with the Purkinje effect, the discrepancy being therefore a conse-
quence of physical intensity; this view has not, however, been
generally accepted. Recently, G. J. Burch has published the
results of some interesting experiments on achromatic thresholds (°).
In the first place, Burch performed some qualitative experiments.
A Bunsen burner was completely covered by a metal chimney so
as to prevent any escape of light while not interfering with ventila-
tion. By bringing the flame into contact with the metal chimney
the latter could-be heated gradually to a point at which it became
luminous. If the experiment were performed in a room with
windows covered by ordinary blinds—that is to say, in a room
from which light had not been absolutely’ excluded—the first
appearance of light was a pearl-grey tint—the achromatic
threshold—as had been previously stated. But when the room
‘was changed to one without windows and absolutely dark,
the first appearance of luminosity was not grey but dull red.
On repeating this experiment, after spending a few minutes
in a lighted room, the former grey appearance was once more
obtained.

Burch then made exact. measurements, using spectral red
and violet, a Nicol prism and paper reflector (Fig. 1). He
found that after a prolonged rest in total darkness, a period
of two hours being necessary, no achromatic threshold existed
for either light.

Adaptation Values (Burch).
A. During the period of increasing adaptation.

STUDIES IN SPECIAL SENSE PHYSIOLOGY 357

I i I of
or ee Minimum Visible | Minimum Visible | Ratio, V : R.
Red, Blue- Violet.
9 16°63 254°76 15°32
21 11-14 5761 5:17
60 9-4 5:39 2:24

B. After spending two hours in the dark room.

EEE ———
-

__ Intensi
—_—* Sis “Mintnum Visible | Mintmum Visible Ratio, V : R.
(Mins. Red. Blue-Violet.
120, 10 1-0 10
122 | 1-20 1°63 1-34
125 2:69 514 191
127 5-04 12:44 2°47
130 50-02 225°72 4-51
C
vy
D
B / is
7

le

relative in

A Raped pre)

358 STUDIES IN SPECIAL SENSE PHYSIOLOGY

Burch, therefore, while confirming the statement that adapta-
tion increases the stimulus value of blue-violet relatively to that |
of red, inferred that the achromatic threshold had no existence,
and that the positive results obtained by other workers were due
to a compounding of the immediate stimulus with the effects of
previous exposure to light—z.e. after-images. By careful observa-
tions in a dark room he ascertained that diffused luminous effects—
his “dazzle tints ”’—persist for as long as two and a half hours
after entering the dark room, and that when these had disappeared
no achromatic interval existed for his own eye.

This evidence is sufficiently strong to render the existence of
an absolute as distinct from a specific threshold for coloured light
exceedingly doubtful in the case of foveal vision. On the other
hand, it is not clear from Burch’s paper that special attention was,
or could be, paid to the behaviour of the periphery ; so that we are
not entitled to conclude from it that an achromatic interval does
not exist when the peripheral retina is stimulated; indeed the
careful researches of Tschermak and others, who worked with pro-
longed dark adaptation (7), are opposed to such a belief.

Burch’s results merely, I think, emphasise the view I am en-
deavouring to develop that central and peripheral vision differ in q
kind and degree. His work does not appear to be fundamentally |
new, except in experimental technique, for Parinaud in 1898 |
remarked in his most suggestive and valuable book: “At the
fovea, on the contrary, a simple light of sufficient purity is per- .
ceived primarily as a colour, whatever be the intensity of the light, |
or whether the retina be or be not adapted ” (7°, p. 51).

Without therefore going the length of asserting that an
achromatic interval depends in some vague way on previous stimu-
‘lation, we must be very cautious in interpreting results, such as
Stegmann’s, obtained by this method.

So far, then, direct experiment seems to have established the
following points :—

(1) The peripheral regions of the retina are relatively more
sensitive than the fovea to light of moderate or short wave length.

(2) Adaptation to darkness is characterised by an increase in
responsiveness to short waved light, and this change is predomi-
nantly, if not entirely, extra-foveal.

The following tables illustrate these statements. The intensity
values are arbitrary, the measurement of eccentricity 3 is in terms
of the angle subtended at the nodal point.

———— i — lS a
‘ .

STUDIES IN SPECIAL SENSE PHYSIOLOGY 359
A. Relative Stimulus Values of different Spectral Regions (Parinaud‘),

Fraunhofer Lines. | Adapted Retina. | Unadapted Retina. |
B |
c =
: y oa
F 1 sho |
i ue i |

B. Increased Responsiveness of Peripheral Retina (Dark-adapted).
Stimulus: A bluish-white object, 35 degrees in diameter (v. Kries," p. 171).'

;

: : Responsiveness Temporal Nasal

CKrbitrary ap veto in Eooentricity in sal rh

| 10 1-07 0°85 192 |
1-78 1-22 1:06 2-28
712 1:70 1°38 3:08

| 16-02 2°3 1:92 4°22

| 28°48 30 2-58 5°58
44-50 3°75 3°33 | 7:08
64-08 4-04 404 | 808

1 Distances from the fovea centralis of any point on the retina can be con-
veniently measured in terms of the angle subtended at the nodal point by a segment
of the retina cut by a plane passing through the fovea, nodal point, and position of

Cc

Fie. 2.

the object and bounded by a straight line through the nodal point from the object
intersecting the retinal segment and by the principal axis. Z.g. if A be an object,
istorlrra ran and CC a section of the retina, the position (eccentricity) of the

Ra eto br to cage «

360 STUDIES IN SPECIAL SENSE PHYSIOLOGY

We must next consider certain facts which seem to bear in-
directly upon the problem under examination; of these the
most important are connected with the condition of total colour-
blindness.

Total colour-blindness is almost always a congenital defect,
and is characterised, apparently, by a complete absence of colour
perception—in the ordinary sense. A person in this state may
see a spectrum merely as a grey strip unequally bright in the
different regions which seem to us of various colours. To describe
the sensations of a second human being is, of course, an impossi-
bility ; but perhaps we may say, for the sake of comparison and
without pretending to any real precision, that a totally colour-
blind man receives from a coloured print impressions similar to
those excited in ourselves by an uncoloured one. The following |
summary of observations by Hering (!”) will give the reader a
tolerably clear impression of the facts.

The subject was a man of twenty years, whose colour vision
had always been abnormal. He said that he could read without
difficulty, provided the light were not too intense, but that his 1
eyes were readily fatigued by bright illumination. In twilight his
vision was especially good, particularly if the light were very
feeble. On examination, the following results were obtained. No
objective changes were detected with the ophthalmoscope, nor was .
any part of the retina insensitive; there was no scotoma. His
power of distinguishing two spots unequally bright—physically—
was much below that of a normal person, in bright light ; in a dark
room, it was much superior. Working with a spectrum, it was |
found that the area of red which produced any sensation was |
much diminished ; there was shortening of the red end, and those
parts which were effective seemed less bright than to a normal
eye. The violet end, on the other hand, was not shortened, and it
seemed relatively brighter than to the normal “light” eye, while
the region of maximum brightness was in the neighbourhood
of the Fraunhofer E and C lines. Brightness matches between
coloured sectors and mixtures of black and white gave the results
indicated in the table, which contains comparative values for
the normal “light” eye. It is to be noted that the colour-
blind’s matches were valid, 7.e. good matches, for a normal
' “dark” eye.

STUDIES IN SPECIAL SENSE PHYSIOLOGY 361

Hering’s Case of Total Colour-blindness.

et ee ae qe Valency of a
Coloured Circle. — Valency.1 the eloured Olrole tr
White. | Black. | | a Normal “ Light” Eye.
Degrees. | Degrees. | Degrees. Degrees.
Bluish red . ‘ 130 | 3470 | 188 | 40
Yellowish red. 55 . 3545 11-4 46
Orange . «| 870 | 3230 | 43-4 159
Yellow , . | 1366 | 223-5 | 1402 - 283
Arsenic green . | 2280 1820 | 230°5 205
Green . : .| 1520 | 2080 «1555 137
Greenish blue .| 1095 | 2505 = 113-7 89
Ultramarine blue 88-3 2717 | 928 | 34
Violet . ‘ ‘ 475 | 3125 52:7 32

Tests were also carried out by means of an ingenious polari-
scopic method. At one end of a horizontal tube, blackened inside,
a cork plate was fixed; the plate was perforated in the middle
and a doubly refracting prism inserted. The other end of the
tube was closed by a lid in which two equal and symmetrically
placed semicircular openings were made. With this contrivance
the ordinary and extraordinary images obtained by polarisation
appeared to form a series of spherical surfaces when the tube was
directed to a source of light—e.g. a piece of baryta paper stretched
over a glass plate. Between the eye and the prism a small tele-
scope and a Nicol prism were introduced, together with a graduated
arc. The diaphragm of the telescope removed the lateral images,
leaving only two magnified white circles, the halves of which could
have their brightness altered in opposite directions by rotating
the Nicol. In front of one opening in the tube a coloured glass
- was placed, and the Nicol so arranged that for the normal “ dark ”
or for the totally colour-blind eye, both halves appeared equally
bright. - The next table gives the readings for two observers. Some
of the variations may be explained by the fact that the normal-
sighted person was unpractised in this sort of work.

1 For methods of measuring white ‘‘ valency ” consult Hering (1*), p. 567, &c.
For the present purpose the figures in the third column of the table may be regarded

as a recalculation of the amounts of white in the sectors which match the coloured
circles, so as to admit of comparison with the figures of the fourth column.

1}

.
362 STUDIES IN SPECIAL SENSE PHYSIOLOGY

Precisely similar results were obtained in matching spectral
colours. :

Polariscopic Matches (Hering).
Yellow Glass. Blue Glass.

Vo |
“Total Colour-bling. | Normal aoe Total Colour-blina, | Normal ree

Degrees of Rotation. | Degrees of Rotation. || Degrees of Rotation. | Degrees of Rotation.
22:3 22°9 18:2 18°35

22°6 22°6 18-0 17°95
22°3 23-0 18-0 18°15
219 22°5 18°1 18°4
22°3 22°7 17°8 18-9
21:8 23°1

22°1 21°8

‘he analogy between normal vision under conditions of dark
adaptation and the vision of the totally colour-blind will also be
apparent from the next two tables. The first gives the intensity
values of the different parts of the spectrum for a normal “ dark ”
eye, as determined by Schaternikoff (1%), and the second Abney’s
observations (14) on two other cases of total colour-blindness. The
units of intensity in the two cases are not comparable, but it
will be observed that the two maxima occur in the same
part of the spectrum.

“ Twilight” Values of a Spectrum (Schaternikof.).

Wave Length. Intensity Value. | Wave Length. Intensity Value.
In millionths of a In millionths of a
mm. mm.
670°8 18:0 529°3 2736-0
651°8 36°5 §22°3 2532°3
634-3 83:3 515°4 2219°3
6181 216°9 508-7 19440
603°1 423°2 502°2 1475°8
589°3 881-7 490°0 10160
577-1 14249 478°6 633-0
566°4 2110°7 468:0 3645
556°0 2609°7 458°7 208°8
546-0 2899-0 451 1112
537:2 3000'0 443°9 69°6

STUDIES IN SPECIAL SENSE PHYSIOLOGY 363

Luminosity Values of two Cases of Total Colour-blindness (Abney).
(No. 40 in Abney’s scale is close to the E line.)

Scale of Spectrum. K. ba eoaearae P.'s Luminosity Value.
56 25
54 9-0
52 16:0 70
50 275 19-0
48 42°5 39:0
46 61-0 65:0
44 82°5 85:0
42 96°0 98:0
40 100°0 99-0
38 95°5 91:5
36 87°5 90°0
34 750 80:0
32 615 65:0
30 43-0 50°0
28 37:0 36:0
26 30-0 26°5
24 24°0 19°5
22 18°5 14:0
20 14°5 10-0
18 115 ee
16 9-0 55
14 70
12 50 . |
| |

As we have already seen that direct evidence points to dark
adaptation being chiefly an affair of the extra-foveal part of the ©
retina, it is reasonable to suppose that, in the totally colour-blind,
the fovea centralis is relatively insensitive. It has indeed been
asserted that a central scotoma, or totally insensitive area, is
found in these cases, and much dispute has arisen on this point.
Summarising the results of examination, we find that, out of
eighteen cases investigated (Grunert '), in seven an absolute or
relative central or para-central scotoma was definitely made out ;
in the other eleven this was absent. The importance of a central
scotoma has been greatly over-estimated for theoretical reasons,
as we shall see later. In most cases, very imperfect fixation or
actual nystagmus was observed. On reviewing the facts, it will,
I think, be admitted that the agreement in type between the vision
of the totally colour-blind and that of the normal “dark” eye

364 STUDIES IN SPECIAL SENSE PHYSIOLOGY

is exceedingly close. The importance of these facts in forming
conclusions as to the mechanism of visual processes will be pointed
out when we have considered a few more experimental observa-
tions regarding central and peripheral vision in the two phases of
adaptation...

A set of experiments, apparently of little practical import-
ance, has proved very interesting with respect to the phenomena
of adaptation. These deal with the effects which follow the
application of luminous stimuli for very short intervals of
time.

Such experiments can be carried out in at least two ways.
By a contrivance, similar to a photographic camera shutter, the eye
can be stimulated for a very short time, or, the gaze being fixed, a
source of light may be moved across the field of vision. For the -
latter experiment, we may employ a rotating mirror and a pro-
jection lantern, or a disc with a slit in it may be rotated in front of
a source of light. If the length of the object be J and v be the
velocity of movement, then J/v measures the time during which
each retinal area is exposed to the action of the stimulus, and by
a suitable choice of object and velocity this time becomes as short
as we please.

In principle the methods are alike, but the second is easier in
practice, and the results obtained of special interest.

The earliest observer seems to have been D’Arcy (}), who, in
1765, measured the duration of the response produced by a glow-
ing coal which was attached to the circumference of a wheel; the
wheel was rotated faster and faster until a complete circle of light
was seen. If a bright object be rotated against a dark back-
ground, in the manner described, the whole sensory effect is some-
what complicated, comprising under favourable circumstances the
following six phases : —

(1) A primary image; the immediate consequence of the
stimulus, its first and strongest effect. As compared with the
image due to a stationary illuminant it is more or less elongated
into a streak of light.

(2) Immediately following upon the primary image is a short
dark streak.

(3) After the dark streak we obtain a second phase of illumina-
tion which, if the stimulus be coloured, appears complementarily
tinged (this is often called, after its discoverer, the Purkinje after-

; at.

STUDIES IN SPECIAL SENSE PHYSIOLOGY 365

image). This phase, which is the most striking part of the whole
experiment, produces the effect of a second bright object coming
behind the first, so that its appearance was termed “ recurrent
vision ” (Young, Davis), the “ ghost ” (Bidwell), or the “ satellite ”
(Hamaker).

(4) The end of the satellite is not sharply defined and is followed
by another interval of darkness.

(5) After this, the field once more brightens, and a faint bright
or homoiochromatic phase is obtained (of the same colour as the
original stimulus). If this part of the phenomenon be well de-
veloped, it is found that with a velocity such that the satellite is
distinct a bright haze fills the whole field, hence more than one
- rotation should not be made.

(6) Sixthly, and lastly, another dark interval occurs.

It will be plain, even from this enumeration, that the phenomena
under consideration are by no means simple; hence nobody will
be surprised to learn that divergences, even flat contradictions,
exist in the literature of the subject not merely as to the inter-
pretation of these results, but even as to their bona-fide existence.
I shall follow, for the most part, the lucid statement of the case
which we owe to Professor J. von Kries(!"), indicating why I
believe his results to be reliable.

With respect to the experiment as a whole, we have three
phases of illumination—the primary image, the secondary or
satellite image, and the tertiary. In apparent brightness, these are
arranged in the order of their appearance. With low illuminations,
primary and secondary images alone are visible; with still lower
intensities, the secondary also disappears. Further, the lengths
of the images can be made to vary, the dark intervals being lost.
Fixing our attention for a moment on the primary, we may note
the following points. Very frequently it exhibits a striped appear-
ance, similar to the well-known Charpentier “‘ bands” (1) seen on
slow rotation of a white field. containing a black sector. Apart
from this, it seems to the “light” eye uniformly bright.~ As,
however, dark adaptation proceeds, we find that the primary
image not only increases in extension and brightness, but with
chromatic stimuli ceases to be uniform. Thus, with blue light,
only the anterior border is deep blue, being followed by a white
stripe. Macdougall (?*) finds this latter to commence at a distance
corresponding, in his experiments, to a time interval of y's second.

366 STUDIES IN SPECIAL SENSE PHYSIOLOGY

With other colours, except red, the same result is obtained, but.
less distinctly.
Although anticipating our theoretical summary, I must point out
how strongly this suggests the activity of two distinct mechanisms
with different latent periods. An analogous, but not identical,
result is the old illusion of the “ fluttering hearts.” Small heart-
shaped scraps of blue paper are pasted upon a red surface and the
whole examined in dim light. On moving the sheet backwards
and forwards, the blue scraps appear to lag behind the red back-
ground. This phenomenon does not occur on stimulation of the
fovea centralis.
The secondary, ghost, or satellite, begins } to ¢ second after the
commencement of the primary, and is, in general, complementary
to it. This rule must, however, be modified in the following way. —
If the primary be pure white, the secondary is bluish; indeed, the
secondary is always modified in the direction of bluishness. Even
with a feeble blue primary, the secondary may still be bluish. - It
is only with a saturated blue primary that a secondary of a really
complementary (yellow) hue is obtained. As regards brightness,
the result depends on the adaptation value of the primary. Two
lights of equal stimulus values for the “dark” eye give equally
bright secondaries. Red, with its relatively low stimulating power
as regards the “ dark ”’ eye, only gives a secondary when its physical
brightness is great.
As we should expect from its characteristics, the secondary is
dependent on dark adaptation, increasing to a maximum of dis-
tinctness as adaptation proceeds and then diminishing, although
Macdougall has obtained it after prolonged dark adaptation. We
thus see in the causative factors of the secondary image the pheno-
mena we have already learned to associate with peripheral vision :
(1) Relatively greater efficiency of short waves; (2) increased in-
tensity with increasing dark adaptation. It only remains to add
failure over the fovea centralis. “If one observes it in the form
of an after-coming image and fixates carefully a luminous point in
the track of ‘the object, one sees clearly that the satellite leaps
over a small central area, while it follows without a break similar
points of light moved over a paracentral region. Also, with
stationary objects, momentarily illuminated, of suitable form and
size, an analogous appearance can be demonstrated. Small objects
which lie entirely within the foveal region do not exhibit the

STUDIES IN SPECIAL SENSE PHYSIOLOGY = 367

characteristic secondary illumination ; small lines passing through
the fixation point exhibit a distinct interruption in the secondary
image ” (v. Kries,'” p. 225).
_ The great theoretical importance of this failure at the centrum
has led to much, at times, acrimonious discussion. Hess (2°) ob-
jected that v. Kries’ experiments were vitiated by the use of bright
objects as fixation marks and too short intervals between successive
stimulations. He showed that no interruption of the secondary
image of a bright line occurred at the fovea, and obtained with
chromatic stimuli similar results, except that for strong red light
the secondary was not complementary but homoiochromatic.
Hess, accordingly, was of opinion that no central difference exists
with regard to the secondary image.

These objections have been considered by v. Kries in an
interesting and lucid article (*").

Failure of a central secondary can be demonstrated by rotating
a screen with a slit in it before an ordinary projection lantern.
The best results are obtained with an arrangement such that the
object takes the form of a line 4° to 4° broad. If adaptation and
physical brightness are so chosen that the secondary is distinctly
separated from the primary, the latter’s failure over the fovea
is clearly demonstrated. Experiments conducted without bright
fixation points and with long intervals between the successive stimu-
lations gave the same results.- V. Kries, however, found that the
experiment failed if crossed lines were used or three small fields in
a row. This seems to be due to psychological factors, especially
the difficulty of concentrating the attention on any particular
point. Thus in the line experiments of Hess, the failure to obtain
a central interruption may be referred to an inability to fixate
steadily any given point, so that the relations of the moving images
are disturbed and a distinction becomes impossible.

_ The results of v. Kries have been essentially confirmed by
Macdougall (#*), and Hamaker (**) also failed to obtain foveal
secondaries for blue and green stimuli. On the whole, the evidence
in favour of v. Kries’ view is strong, and we may consider the third
point suggesting the peripheral nature of the secondary image—
its failure at the fovea—as established.

Passing to the tertiary image, the following characteristics
have been made out. The hue is best appreciated when one uses
red light, and may, in this case, be very distinct. With increasing

368 STUDIES IN SPECIAL SENSE PHYSIOLOGY .

dark adaptation, the tertiary gains in brightness and loses in
chromatic value ; indeed, owing to the high adaptive powers of blue
and green lights, when these are used at moderate intensities, the
colouration of the tertiary image is only visible at the beginning
of the experiment.

There is some difference of opinion as to whether the tertiary
can be obtained in direct vision ; since red light is the most suit-
able stimulus for calling up this image, it is reasonable to suppose
that it should be perceived by direct fixation. The suggestion is,
therefore, that the customary form of the tertiary image is due to
a chromatic element, unaffected by dark adaptation, and a bright-
ness element which is so affected.

We are almost in a position to attempt a sorting out of the
various experimental facts described ; only one group remains
for examination, namely, some researches into peripheral changes
which accompany the retinal alterations, and are important as
objective signs of the latter.

Schirmer asserted that the pupil width and its reaction were
related to the adaptive condition of the eye. With complete
adaptation to a given grade of light, the pupil reaches after initial
widening or narrowing a physiological mean position. Garten (?%)
found that momentary illumination produces in the “light ” eye
a weak sudden, in the “dark” eye a slow powerful contraction.
Proceeding further on these lines, Sachs (?*) discovered that the
pupillo-motor response to coloured lights followed closely their
adaptation values. Abelsdorff (?*) confirmed these results, using
the apparatus sketched (Fig. 3). One of the two lights serves as a
standard ; the subject looking through the strong convex lens at the
slit sees a bright point surrounded by a diffusion circle. If the light
falling on the eye be changed the diffusion circle increases or
diminishes in size. By rotation of a Nicol prism the new intensity
can be increased or diminished and the intensity is found for which
the diffusion circle produced by the standard light is not increased
or diminished by changing to the tested colour. Naturally, the
method does not yield very exact quantitative measurements ; the
mean error is said to be about 7 per cent. The next table (see
p- 370) gives some of Abelsdorff’s results.

; The close agreement between the pupillo-motor values and
those of apparent brightness justifies the method, and its importance
lies in the fact that we can employ it in experiments on animals.

—— a

STUDIES IN SPECIAL SENSE PHYSIOLOGY 369

We have no direct means of investigating adaptive changes in any
animals except man, but we can measure this pupillary response ;
if we find it changing in the manner described, it is not an unfair
inference to suppose that visual responsiveness may be similarly
affected by adaptation.

It has been found that intensities of red and blue which ap-
peared equally bright to and exerted the same pupillo-motor effect
upon a human “light” eye, did not produce identical changes

pone 9 ae Triplex Lamp.

Slit in Telescope.
=~} Separating Prism.

}- Oytinder of Blacked Paper 55 o.m.long.

<—— Conve Lens. Focal Length 10 cm.

) Unaccommodated Eye.

Fie, 3.—Abelsdorff’s apparatus for studying the pupillo-motor response.

_ in the pupils of the dove and the owl. For the former the red,
for the latter the blue was the stronger stimulus. Indeed the
pupillo-motor response to blue ‘in the owl’s eye was greater than
in the case of a total-colour-blind (Abelsdorff).

We have now completed a brief review of the experimental
facts and are at liberty to consider their importance in our general
conception of visual processes.

First of all, is there any functional difference between the spot
of distinctest vision, the fovea centralis retine, and the paracentral
or peripheral regions of the retina ?

= 2A

370 STUDIES IN SPECIAL SENSE PHYSIOLOGY —
Pupillo-Motor Values.

Comparison Lights.
Wave Length. | Dark Adacholl

rire 600 pn. Light Soe | ar’ nee tion.

Mm. Mm. | Mm.
640 6271 *3920 "2666
620 8523 8376 | *5670
600 9720 9822 ‘7260
580 9536 ‘9090 | *8065
560 8303 8739 *8865
540 5518 6141 | 9200
520 3333 | 2936 ‘5755
500 1181 | ‘09141 "1612

Brightness Values.

(Readings obtained when the same subject adjusted the intensities of
the lights until they seemed to be equally bright.)

Comparison Lights.
Wave Length. : ae ae ae:
py. 600 pup. Light Pp i Dark Pep aa
| Mm. Mm. Mm.
640 | 5253 | *3518 2529
620 | 8204 ‘7230 ‘5515
600 | 9431 9090 8536
580 ~ | 9431 ‘9090 8535
560 ‘8811 ‘8613 "9540
540 6259 6354 "9540
520 *3700 *3189 ‘5750
500 ‘1168 0944 i "1612

In view of the long series of experiments bearing upon the
Purkinje effect, the increase in brightness of the short waved
spectral lights at the expense of the long waved vibrations, the
reader is probably satisfied that this effect if not solely peripheral
is at least mainly so. I do not wish to disregard those who haye
obtained central adaptation, but even they admit the increase
to be far less marked than the peripheral alterations; we may,
without undue scepticism, entertain some doubts as to whether the
positive results might not have been due to some slight eccentricity
of fixation. However that may be, we are beyond question

STUDIES IN SPECIAL SENSE PHYSIOLOGY 371

justified in assigning to the periphery a predominating share in
the work of dark adaptation.

We have also seen that these adaptive changes consist in a
greatly increased responsiveness to light of short wave length,
such appearing more intense than under “ light ” conditions.

We have thus to account theoretically for a localised change in
responsiveness with respect to certain forms of stimulation.

The difference in histological structure between the fovea
centralis and the surrounding area caused Schultze forty years
ago (*4) to suggest a functional separation which he supported
on evidence drawn from comparative anatomy. In his time,
however, our experimental knowledge of adaptive changes was
little advanced and his conception went unheeded. The first de-
tailed investigation was due to H. Parinaud (”°), who has developed
a theory of adaptation in a series of memoirs dating from 1881.
Similar views have been carefully elaborated by Professor J. v.
Kries of Freiburg and his colleagues and pupils in a large number
of well-planned researches.

Essentially the theories of Parinaud and v. Kries may be
summarised quite simply. Two distinct visual mechanisms exist :
one, subserving both chromatic and achromatic responsiveness, and
represented in the retina by the cones; the other dealing with
achromatic sensations alone, represented by the rods and visual
purple. The former mechanisni is alone active in bright daylight
and is unaffected by resting in the dark ; the latter is brought into
play by shielding the eye from stimulation, being the sole or chief
agency of twilight vision ; it is characterised by special responsive-
ness to ethereal vibrations of short wave length. In view of the
double nature of the mechanisms postulated, the theory has been
christened the Duplicity Theory (Duplizititstheorie). Let us see
_ how far the hypothesis covers the experimental observations I
have enumerated.

If the theory be true, we should expect (1) spectral maximum
brightness to change in weak light in favour of the violet end ;
(2) this change not to occur for images formed at the fovea
centralis; (3) no achromatic threshold (vid. sup.) to be obtained
for any light at the fovea or for red light anywhere.

We have seen that each of these deductions is supported by
good experimental evidence.

Again, have we any forms of vision in which, apparently, the

-

372 STUDIES IN SPECIAL SENSE PHYSIOLOGY

basal mechanism is similar to that associated by the theory with
twilight vision and uncomplicated by the existence of a second
type of reaction? The subjects of total-colour-blindness appear
to enable us to answer the question affirmatively. We found that
the brightness judgments of these people agree well with those of
normal men in a state of dark adaptation ; that there is evidence
in such cases of diminished or absent foveal sensitivity, bad fixation,
inferior acuteness of vision, nystagmus, central scotoma (some-
times) and abnormally good vision in twilight.

Conversely, are there any cases in which the hypothetical day-
light mechanism alone reacts ?

Parinaud (1°) has investigated several cases of “night-blindness ”
or hemeralopia. He found that in such, vision was of the foveal

type ; the colour sense was normal, but the spectrum shortened at.

the violet end ; responsiveness to short waved light was abnormally
low. The investigations of Messmer (7*) and others make it pro-
bable, however, that the condition of night-blindness is not simple,

different forms and degrees being classified under the same heading. ~

In some cases, dark adaptation is very slowly induced, but after
a sufficiently long interval is normal in degree. In others some
adaptation comes on in a normal time but is of inferior extent.
It is important to bear these cautions in mind because night-blind-
ness is markedly heritable and has been used, in the writer’s opinion
illogically, as an argument in favour of the validity of the Mendelian
theory of inheritance. For our present purpose, we must admit
that night-blindness does not afford us so much information re-
specting visual processes as the apparently opposite condition of
total-colour-blindness. Provisionally, we may, perhaps, say that
the latter condition is consistent with the activity of the hypothe-
tical twilight mechanism functioning by itself, while some examples
’ of the former peculiarity suggest that the daylight mechanism alone
exists. But itis to be remembered that scarcely any theory, how-
ever absurd, which has been advanced in explanation of a difficulty
in sense physiology has failed to obtain the support of some patho-
logical phenomena which have been tortured into a semblance of
agreement with its postulates.

The complex results in sensation which follow the application
of short or moving stimuli to the retina have perhaps confused
some readers; let us see whether our hypothesis i is capable of
arranging them in an orderly manner.

*
ile i

STUDIES IN SPECIAL SENSE PHYSIOLOGY 373

I have already pointed out that the peculiar striping of the
primary image, the blue tailing off into white, suggests the interplay
of two processes ; I also emphasised the dependence of the secondary
image on adaptation and its (probable) absence at the fovea. We
can perhaps sum up the effects in terms of our hypothesis thus :—
The cone mechanism responds by two effects, the main part of
the primary and the colour component in the tertiary. The rod
apparatus responds in a threefold manner; it gives us the white
tail of the primary, the whole of the secondary, and contributes,
although slightly, to increasing the brightness of the tertiary.
This way of putting the facts does, I think, clarify our ideas, but
it certainly fails to remove all difficulties. Thus, if we are to
regard our twilight mechanism as solely responsible for the
secondary image, it is clear that we derive sensations of colour as
well as sensations of luminosity without hue from that mechanism,
since the secondary image is often coloured. Hence the mechanism
cannot be identical with that of a totally colour-blind eye ; so that
we must either give up the view that total-colour-blindness is a
condition in which the rods and purple react as in a normal eye,
or regard the secondary as due to something beyond rod stimula-
tion. V. Kries is disposed to adopt the latter alternative, but in
that case it is difficult to understand why the secondary is entirely
peripheral, and therefore how it is that the cones can only respond
with the rods in this case.

This I believe to be the most serious difficulty in the way of an
acceptance of the duplicity hypothesis. It is easy to evade the
objection by transferring the production of secondary images to
the brain (? consciousness), a course adopted by. Parinaud, but this
is undesirable, and I think it better to leave the difficulty where it
is. We can only say, in the stereotyped phrase of the embarrassed

- physiologist, further work is necessary to clear up the point.

We have so far examined the duplicity theory by the light of
the chief experimental facts, but a little more evidence has to be
considered.

It has long been known that the relative numbers of rods and
cones differ in various animals. Thus the rods are very large and
almost exclusively present in the retine of nocturnal animals, such
as owls, bats, and hedgehogs. In many other creatures, on the
other hand, including most birds, cones predominate. It was
indeed on the strength of this that Schultze advanced a theory

374 STUDIES IN SPECIAL SENSE PHYSIOLOGY

essentially similar to the one we are considering. Kiihne subse- —
quently showed (?7) that visual purple was present only in retine
containing rods. He was not, however, able to extract this pig-
ment from all rod-containing eyes, a notable exception being the
bat ; recently, Trendelenburg (7°) has obtained abundance of visual
purple from more than one species of bat. Experimentally, as we
have seen, Abelsdorff has shown that the owl is specially sensitive
to short waves and the dove relatively insensitive (tested by the
pupillo-motor response).

We all know that most nocturnal animals see badly in broad
daylight, while such birds as the pigeon exhibit normally a marked
degree of night-blindness. In Parinaud’s words :—

“It is a matter of common observation that hens and pigeons
see very imperfectly in artificial light and defend themselves with -
difficulty against the hand that tries to seize them; that as soon
as the sun goes down these animals seek their night shelter. The
old adage, ‘To go to bed with the hens,’ meaning to go to bed ©
early, evidently having its origin in this fact ” (1°, p. 66).

Biological investigation appears to show, therefore, a co-
existence of rods and visual purple with vision of the twilight

variety and of cones with optimal vision in daylight. It is easy
~ to lay too much stress on this sort of evidence. Reasoning from
analogy is dangerous and especially equivocal when dealing with
sense physiology. Take the history of opinion regarding a bat’s
vision. The objectors to the theory of duplicity pointed out that
no visual purple had been extracted from the bat’s retina. Its
partisans retorted that the bat relied on sensory mechanisms other
than sight, possibly scent currents, as seems to be the case with
moths. My friend Mr. Arthur Bacot points out to me that the
.temarkably rapid darting movements of a bat in pursuit of prey,
movements which are comparable in point of velocity with the
swift’s flight, seem hardly compatible with the type of twilight
vision we have agreed to associate with the rods, characterised as
that is by poor acuity of vision. We are now aware that many
species of bat possess visual purple. Hence, if the previous train
of reasoning be at all correct, the value of an outfit of rods and
visual purple to the twilight animals is rendered doubtful. In
precisely the same way, the early roosting of diurnal birds may be
due to causes other than a condition of night-blindness.

It is necessary to dwell upon these points because in no de- —

STUDIES IN SPECIAL SENSE PHYSIOLOGY 375

partment of physiology is there a greater tendency to advance
equivocal evidence in favour of an hypothesis than in that con-

cerned with the special senses.

I can now sum up the case presented. I hope I have rendered
it probable that—

(1) There is a marked difference between central and peripheral
vision, in regard to the phenomenon of darkness adaptation, the
former being little if at all affected in the process.

(2) These differences may be provisionally interpreted on the
supposition that visual sensations are bound up with two distinct
mechanisms : (a) That of the cones, with which chromatic sensitivity
and achromatic sensations under daylight conditions are associated ;
(b) that of the rods upon which depend achromatic sensations
under conditions of dark adaptation.

The objections to this view are neither few nor unimportant.
It has not been proved that no central adaptation whatever occurs.
The equations (colour matches) of totally colour-blind persons and
those of the normal “dark” eye agree well but not absolutely.
There is also a difficulty in interpreting the secondary image of
recurrent vision.

That the first of these objections (as well as the kindred one
that a central scotoma does not exist in all cases of total-colour-—
blindness) may be parried by supposing a trace of visual purple
and a few scattered rods to be present in the fovea, isclear. Recent
measurement by Fritsch (!7, p. 188) on a negro’s fovea gave an
absolutely rod-free zone of only ‘2 mm., corresponding to an ~
angular distance of less than a degree ; we could not allow much
weight to failures in the demonstration of such small adaptable
areas, even supposing them to be absolutely rod-free.

The difficulty regarding ‘‘total-colour-blinds” and normal
“dark” equations is not formidable. The fact is that sufficient
measurements have not been made to enable us to affirm that the
differences are significant. The more serious question as to the real
significance of the secondary image in recurrent vision has been
already considered ; it may prove the crucial point in the theory.
Accepting the above view of the réle of the visual purple and rods
as an important element in the physiological processes of vision
with low intensities of light, one is tempted to speculate as to the
nature of their activity. Parinaud was of opinion that the process
depended upon fluorescence of the retina mainly due to the presence

376 STUDIES IN SPECIAL SENSE PHYSIOLOGY

of visual purple. This view is certainly incorrect. A bleached
retina is more strongly fluorescent than one in which the visual
purple is unreduced (Kiihne 2’), although the bleached substance
itself may possess fluorescent properties, since Nagel and
Himstedt (?8) observed that a bleached solution of visual purple
was more strongly fluorescent than the solvent alone.

_ If then we accept, as a working hypothesis, the view that the
rods and visual purple form a link in the chain of processes by
means of which certain forms of stimuli are, under particular
conditions, associated with sensations, we must not, in the present
state of the question, attempt to assign to them any precise
physical or physiological share in the process.

In conclusion, the reader need not suppose that the cones of
the periphery are functionless, that in broad daylight peripheral .
vision is at all of the type we have been studying. As a matter of
fact, at the extreme periphery which is normally quite colour-blind,
brightness values are altogether different from those of the “ dark ”
eye, as is shown in the following table (v. Kries,!” p. 199) :—

Na line=100

Wave length. . 680 651 629 608 589 573 558 530 513
Peripheral value :
daylight . . 96 375 1775 101 100 796 522 285 146
Peripheral value
twilight . . 2? 34 140 35:5 100 256 351 321 198

The study of this problem of visual adaptation illustrates well
the patient and laborious experimental work necessary to de-
monstrate even a limited range of phenomena, the complexity of
results which appear at first simple and the necessity of caution
in framing satisfactory hypotheses. It has been chosen to de-
scribe because it is so instructive from these points of view.

BIBLIOGRAPHY

(This list is not, of course, complete. The papers marked with an asterisk
contain extensive bibliographies, )

1 Charpentier, Arch, d’Opthalmologie, vol. iv., pp. 291-323.

* A, Tschermak, Pfliiger’s Arch., vol. 70, pp. 297-328, A critical summary
* of work up to 1902 will be found in * Die Helldunkeladaptation des Auges
und die Funktion der Stabchen und Zapfen, by A. Tschermak, Ergebnisse
der Physiologie, lst Jahrgang, 2nd part, pp. 695, &c.

Po
_
7

—

STUDIES IN SPECIAL SENSE PHYSIOLOGY 377

® Hering, Pfliig. Arch,, vol. 60, pp. 519-642.

* Haycraft, Journal of Phy-iology, vol. 21, p. 126.

® Rivers, Journ, of Physiol., vol. 22, p. 137.

* Hering, Pfliig. Arch., vol. 47, », 417.

_ 7 V. Kries and Nagel, Zeitschrift f. Psychol. u. Physiol. der Sinnesorgane,
vol. 23, p. 161.

* Tschermak, Ergeb. d. Physiol., 1st Jahrg., 2nd part, p. 731.

* Burch, Proc. Roy. Soc., B, vol. 76, p. 199. See also Nagel and Schaefer,
Zeits. f. Psy. u. Phys, d. Sinnes., vol. 34, p. 271; Loeser, ibid., vol. 36, p. 1.

%” Parinaud, La Vision, Paris, 1898 (Doin), p. 51.

u* J. v. Kries, Die Gesichtsempfindungen, Handb. d. Physiol. d. Mensch.,
herausgegeben v. W. Nagel, vol. 3, pp. 109-282.

1 Hering, Pfliig. Arch., vol. 49, p. 563.

1% Schaternikoff, Zeits, f. Psy. u. Phys. d. Sinnes., vol. 29, p, 255. See also
Fujita, tbid., vol. 43 (pt. ii.), p. 243.

* Abney, Proc, Roy. Soc,, vol. 66, p. 179.

* * Crunert, Arch. f. Opthalmol., vol. 56, p. 182. Other papers on total-
colour-blindness are :—Hering, Pfliig. Arch., vol. 49, p. 563, Hess, Zeits. f,
Psy, u. Phys, d. Sinnes., vol. 29, p. 99. Hess and Hering, Pfliig. Arch., vol.
71, p. 105. V. Hippel, Klinische Monatsblatter f. Augenheilkunde, vol. 36,
p. 324. Nagel, Zeits. f. Psy. u. Phys. d. Sinnes., vol. 29, p. 118. Uhtoff,
Zeits. f. Psy. u. Phys. d. Sinnes., vol. 20, p. 326; and vol. 27, p. 344.

#® Quoted in * Helmholtz’s Handbuch d. Physiol. Optik., 2nd edit., p. 501.

" V. Kries, Nagel’s Handb. d. Physiol., &c., vol. 3, pp. 220-226.

8 Charpentier, Archives de Physiol., 1892, p. 541; also C. R. de l’Acad.
des Sciences, vol. 113, p. 149.

%” Macdougall, liritish Journal of Psychology, vol. 1, p. 78.

® Hess, Zeits. f. Psy. u. Phys. d. Sinnes., vol. 27, p. 1.

1 V. Kries, Zeits. f. Psy. u. Phys. d. Sinnes., vol. 29, p. 81.

* Hamaker, Zeits. f. Psy. u. Phys. d. Sinnes., vol. 21, p. 1.. Other
papers on recurrent vision are :—Bidwell, Proc. Roy. Soc., vol. 56, p. 132.
Charpentier, C. R. de PAcad. d. Scien., vol. 113, p. 149. Hess, Pfliig. Arch.,
vol. 49, p. 190. Hess, Arch. f. Opthalmol., vol. 44, p. 445; vol. 51, p. 225.
V. Kries, Zeits. f. Psy. u. Phys. d. Sinnes., vol. 12, p. 81; vol. 19, p. 175;
vol. 25, p. 239.

* Garten, Pfliig. Arch., vol. 68, p. 68. Sachs, Pfliig. Arch., vol. 52, p. 79.

- Abelsdorff, Zeits. f. Psy. u. Pliys. d. Sinnes., vol. 22, pp. 81, 451; vol. 34,

p. 111 (with Feitchenfeld).

* Schultze, Arch, f. Mikrosk. Anatm., vol. 2, pp. 175-273.

* Parinaud, Arch, Génér, de Med., 7th Series, vol. 7 (1881), pp. 403-414.
C. R. de Acad. d. Sciences, vol. 93, p. 286.

** Messmer, Zeits, f. Psy..u. Phys. d. Sinnes. (2te Abth. f. Sinnes-
physiologie (1907), vol. 42, p. 83.

* Kiihne, Hermann’s Handbuch der Phys., vol. 3, p. 235 (twenty-two
other papers published, 1877-9).

* Trendelenburg, Arch. f. Physiol., 1904, Suppl. Bnd., p. 228.

*® Nagel and Himstedt, Festschr, d. Univ. Freiburg i. Br., 1902 (quoted
in Nagel’s Handb., vol. 3, p. 96). .

STUDIES IN SPECIAL SENSE PHYSIOLOGY
PART II

Section [I.—HistToricAL INTRODUCTION

Any one who examines the current text-books of physiology
will find that in discussing colour vision great prominence is
given to two theories, those of Helmholtz and Hering respectively.
As the reader will also find it admitted that neither theory resumes ©
in an altogether satisfactory manner the data of observation and
experiment, he may be tempted to ask why so much stress is put
upon them. An obvious explanation is the authority attaching -
to any utterances of men who have notably advanced our know-
ledge in various fields. This cannot, however, be the sole reason ;
physiologists not less distinguished than Helmholtz and Hering have
before now promulgated theories which, being inconsistent with the
subsequent results of investigation, have perished. The vitality
of these particular theories of colour vision must therefore be
referred to some.principle other than that of mere authority.

The object of this essay is to show that these admittedly in-
complete theories are important because each brings into prominence
one aspect of the problem; the harmonising of these two aspects
must occupy those who come after us and examine the question
‘ by the light of fuller knowledge than we possess.

With this end in view, it will be necessary, before considering
the theories themselves and their relation to known facts, to
examine briefly some opinions as to the nature of visual processes
which were held long ago but have by no means lost all interest
for us. Of these speculations, the most important are due to the
Greek philosophers and men of science.

In attempting to estimate the scientific value of the Greek —
theories of vision, it is necessary to bear in mind certain limitations

1 A valuable account of Greek Sense Physiology and Psychology will be found

in “Greek Theories of Elementary Cognition from Alemzon to Aristotle,” by
Professor J. I. Beare (Clarendon Press, bt: p- 354).

STUDIES IN SPECIAL SENSE PHYSIOLOGY = 379

which were imposed upon them by imperfect means of investiga-
tion. Even with modern apparatus, it is not easy to obtain a pre-
cise idea of the elaborate structures contained in the eye—as every
student knows—hence workers unprovided with the simplest
microscope knew almost nothing of what is now common know-
ledge. Roughly, we may say that all the early theories agree in
regarding the “ pupil” of the eye and the “image” within it as
of primary importance. Again, the flash of light seen on pressing
or rapidly moving the eye was held to prove the existence of an
inherent or native “fire,” also of great significance. Thirdly, the
presence of a watery substance within the eyeball had to be
accounted for. The problem, as it presented itself to the earliest
writers, was to assign: their proper shares in the visual act to the
“ fire,” the “image,” and the “ water.”

One of the earliest of the Greek writers on this subject was
Alemeon of Cretona (fl. B.c. 500). Our knowledge of his views
seems fragmentary; he thought that seeing is accomplished by
rays passing from the ocular “ fire’ to the object, and that these
returning to the eye, altered in some way, are reflected in the
diaphanous “ water.” The “fire” is therefore the active element
in vision. The hypothesis hardly appears consistent with itself,
because the conception of a visual ray from the “ fire”? cannot
readily be harmonised with a mirror-like action of the “‘ water.”

Empedocles’ (circa B.c. 450) theory was more subtle and
elaborate, although it is not easy to reconcile different statements
attributed to him.

According to the first doctrine enunciated by Empedocles,
like perceives like. All bodies whatever are characterised by—
(1) All are made up of four elements, earth, air, fire, and water.
(2) All are permeated by minute passages or pores, and all give
- off emanations which enter the pores. Thus, in perception, emana-
tions from the object pass into the pores of the percipient organ.!
But, that this passage may be effected, it is necessary that the
emanations and the pores should correspond ; if the former are
too large or too small for the latter, no perception can occur.

Hence with the eye alone can we perceive emanations of colour

1 Cf. Lucretius, De Rer. Nat., bk. ii., 833—

* Noscere ut hine possis prius onmem efflare colorem
Particulas, quam discedant ad semina rerum.”
See also bk. iv., 72-86. :

380 STUDIES IN SPECIAL SENSE PHYSIOLOGY

because these are “ symmetrical” with the pores of the eye alone.
This correspondence is the basis of sense specificity. Further
there is a symmetrical arrangement within the eye itself with
respect to the different forms of stimulation. By means of the
intra-ocular fire we perceive the emanations of fire—i.e. white—
with the “‘ water” we see water—1.e. black—and so on.

“With earth we see earth, with water we see water, with air
we see the bright air; just as with love we (perceive) love, and
with hate, baleful hate” (1). Empedocles is said to have regarded
four colours, white, black, red, and green, as primaries (Stobeeus),
but only examines white and black in detail. He also taught
that rays issued from the visual “fire,” but how this process was
associated with his general doctrine of pores and emanations is
not certain.

Democritus (? 460-357) agreed with Empedocles in postulating
the entrance of particles from an object into pores contained in the
perceiving structure and in the dictum that “like is perceived by
like.” But he denied that there are four qualitatively distinct
elements, and believed that all things are made up of homogeneous
atoms moving in a vacuum and infinitely numerous. Vision is
due to the mirroring of an object in the eye, the latter’s character F
being somehow determined by its moist and porous nature. This
part of Democritus’ theory was sharply criticised by Aristotle,
who remarked : “ It is absurd also that it should not have occurred
to him to doubt why the eye alone sees, but nothing else in which
energies are apparent. That the sight is aqueous is true; yet it
does not happen that it sees because it is aqueous but because it
is diaphanous, which is also common to air” (2).

Democritus seems to have been the first writer to attempt a
detailed theory of colours, the simple ones being white, black, red,
and green; his account, which is somewhat elaborate, has not
played a sufficiently important part in the history of opinion to
need further description, but it is well to remember that he (anti-
cipating Berkeley!) held that colour had no objective reality.
“ ... the ultimate\elements—the plenum and the vacwum—are
destitute of all sensible qualities, while the things composed of
them possess colour (as they do every sensible quality) owing
merely to the order, figure, and position of the atoms, i.e. (a) to their

1 Cf. ‘*The First Dialogue between Hylas and Philonous,” especially pp. 314-
318 (Sampson's edition, vol. i.). Lucretius, loc. cit.

STUDIES IN SPECIAL SENSE PHYSIOLOGY 38l

order relatively to one another; (b) to their several shapes; and
(c) to the position of each in its place. The subjective aspects—
the qualities—of sensible objects are all due to these three things.
Colour has no objective existence, since the colours of bodies are
due to the position of the atoms in them ” (°).

The views of Anaxagoras (B.c. 499-428) and Diogenes of
Apollonia (5th cent. B.c.) may be passed over rapidly. Anaxagoras
held, in opposition to his contemporaries, although the opposition
is more formal than real, that perception is the result not of like
operating upon like, but of the reaction between contrary and
contrary. The “image ” is not reflected upon a part of like colour
to the object but upon a different colour. Diogenes, who be-
lieved that an all-pervading “air” was the ultimate agency in
nature, has left no distinct theory of colour vision.

One would naturally expect that Plato (429-347), to whom we
now turn, would have powerfully contributed to the advancement
of our knowledge of the physiological psychology of vision, but
this is not the case. His account of the physical side of the
problem is contained in a passage in the “ Timzus,” of which the
following quotation gives an idea :—

** And of the organs they first contrived the eyes to give light,
fixing them by a cause on this wise. They contrived that as much
of fire as would not have the power of burning, but would only
give a gentle light, the light ‘of every-day life, should be formed
into a body; and the pure fire which is within us and akin to
this they made to flow through the eyes in a single entire and ~
smooth substance, at the same time compressing the centre of the
eye so as to retain all the grosser element and only to allow this
to be sifted through pure. When therefore the light of day sur-
rounds the stream of vision, then like falls upon like, and there
is a union, and one body is formed by natural affinity according
to the direction of the eyes, wherever the light that falls from
within meets that which comes from an external body. And
everything being affected by likeness, whatever touches or is
touched by the stream of vision, their motions are diffused. over
the whole body and reach the soul, producing that perception
which we call sight ” (*).

In the genesis of colour, particles are discharged from external
things and impinge upon the eye, some being larger, some smaller,
and some equal in magnitude to the parts of the eye. All colours

382 STUDIES IN SPECIAL SENSE PHYSIOLOGY

are compounded of four; white, black, bright, and red. Bright
when mixed with red and white becomes golden-yellow; red
blended with black and white yields violet.

From statements in the “ Timzus” and “ Republic ” it would
seem that Plato, unlike Democritus, believed in the objective
existence of colour in things; but, as Helmholtz remarks (°), his
views seem to have varied. In the “ Theetetus,” colour is con-
sidered from an entirely different standpoint, as will be clear from {
the next quotation :—

‘We shall see that every colour, white, black, and every other
colour, arises out of the eye meeting the appropriate motion, and
that what we term the substance of each colour is neither the
active nor the passive element, but something which passes between
them and is peculiar to each percipient. . . .”

‘““When the eye and the appropriate object meet together
and give birth to whiteness and the sensation of whiteness which
could not have been given by either of them going to any other _ |
object ; while the sight is flowing from the eye, and whiteness
from the colour-producing element, the eye becomes fulfilled with
sight and sees, and becomes not sight but a seeing eye ; the object
which combines in forming the colour is fulfilled with whiteness
and becomes not whiteness but white ” (°).

Aristotle’s (B.c. 384-322) theory of vision is of very great
importance in the further development of the subject, and indeed
still survives in a modified form. We must therefore examine it
more closely.

According to Aristotle, the object of sight is colour. Colour
is at the surface of all visible objects, but, in order to be seen,
requires the presence of light, which is the medium of vision.?

Light again pre-supposes a diaphanous substrate which in its
turn is the medium of light. Examples of this “‘ diaphanous ” are
air, water, and many solids. The realisation or actualisation of
this potential quality of being diaphanous is light, its absence
darkness. When the former condition of actual light is estab-
lished in the diaphanous medium, any coloured body sets up a

——.

1 Of. Lucretius, De Rer. Nat., bk. ii., 795—

‘* Praeteria quoniam nequent sine luce colores
Esse, neque in lucem existunt primordia rerum,
Scire licet quam sint nullo velata colore.”

The whole passage, from 730 to 833, is of much interest in this connection.

~~

STUDIES IN SPECIAL SENSE PHYSIOLOGY 383

movement in it, between object and eye; this is the essential
process in colour perception.

The diaphanous substrate, upon which depends the existence
of light and, a fortiori, colour, is not peculiar to the bodies called
transparent or diaphanous, but is a species of universally diffused
natural power ; it is not indeed capable of existence independently
of “body” but subsists in varying degrees in all bodies. The
colour of a body either forms its surface or is upon that surface,
the latter opinion being the more exact since the indeterminate
“diaphanous” of air and water exhibits colour, which, however,
owing to the indeterminate boundary, is variable. This explains
_ the changing hues of sea or sky.

Bodies with a definite boundary have a fixed colour, so that
one might again define colour as the surface limit of the “ dia-
phanous ” in determinately bounded body. This definition is con-
sistent with the first given, viz. that which stimulates the actualised
“diaphanous”’ (light) between the object and the eye, but the
latter is a definition in terms of vision and the medium of vision,
the former in terms of the object as it exists apart from vision.

Colour is a genus comprising seven species ; it is a quality and
cannot therefore exist without a substrate. The seven species are
white, black, golden-yellow, crimson, violet, leek-green, and deep
blue. The colour genus (like all other genera of sensible qualities)
consists of species lying between extremes ; outside these extremes
there can be no colours, between them are specific boundaries.
By subdividing the scale limited by the extremes, we cannot _
obtain an infinite number of distinct colours because a sensible
quality is discrete not continuous. By dividing the substrate we
do not arrive at any new colour, the halves of a white object are
white. It is true that by sufficiently fine division no colour what-
ever may be perceptible, but on reuniting these portions we again
obtain white. The two limits are black and white; when one is
actually existent the other is only potential. The transition from
white to black is effected through the successive degrees which are
the species of colour. The substratum, of which these are the
qualities, is one, and is in strictness that which is changed; the
colours alternate.

Colour is not purely subjective. It is true that it depends
upon the eye, but it also depends upon the object. Actual colour
depends upon the possibilities of these two being realised together,

384 STUDIES IN SPECIAL SENSE PHYSIOLOGY

but the coloured object existed in nature as a potential colour
before the act of vision and apart from it. “It is light that at once
transforms the potential colour to actuality and the potentially
seeing to an actually seeing eye” (7).

In the colour scale (as among the elements) there is a sort of
opposition of positive and negative. White is the positive, black
the negative. ‘

This is Aristotle’s general account of colour and of the “ dia-
phanous”’ its vehicle—omitting his views of reflection which are
not important from the physiological or psychological standpoint.
He also treats of certain colours in detail.

The presence of some fire-like element is the cause of light in
the diaphanous, and in its absence we have darkness. In all de-
terminately bounded bodies we may assume something analogous .
with the presence and absence of this fiery element. Its absence
means blackness, its presence whiteness. Therefore, in deter-
minately bounded bodies, blackness is privation of whiteness.
Thus, blackness and whiteness are contraries within one sensory _
province, that of colour, and from them all the other colours are
to be explained. “The transition from white to black is possible
through continuous degrees of privation; that from white to
black is likewise possible by an ascending scale in the opposite
direction. The various colours are species which fall between -
the two contraries and are generated of certain combinations of
these’ (8). For instance, in passing from white to black we first
come to crimson. As the intervening stages in the passage mark
relative extremes, change can start from any point.!

With regard to the actual mode of origin of the intermediate
colours, what is actually effected in the above-mentioned process ?
Aristotle discusses and condemns the doctrine of atomic juxta-
position and that of superposition, taking the view that a complete
blending occurred. No individual part of the compound colour
retains its primitive characters unmodified.?

As specific illustrations of this theory, we may take red, which
is produced by light streaming through black, and purple, distin-
guished from crimson in possessing more of the dark ingredient.

|
|

1 Goethe, of course, maintained the correctness of this theory in the Farben-
lehre. (Cf. Goethe’s Theory of Colours, translated by Eastlake, London, 1840.)

* Aristotle does not give this account in all his works. Vide Beare, op. cit.,
pp. 74-76. i

STUDIES IN SPECIAL SENSE PHYSIOLOGY 385

Thus the sun shining through a fog is red; the feebler lamp ray
sometimes appears purple.

In this connection, Aristotle refers to positive and negative
after-images. After looking at the sun and closing the eyes we see
the object at first of the same colour as before ; this changes to
crimson, then to purple, then black, and finally vanishes. This
illustrates the genesis of colours from the blending of black and
white. Simultaneous contrast is explained along these lines—the
brightest rainbow appears in the darkest cloud, white wool has its
colour intensified when placed next black wool, &c.

Aristotle rejected altogether the theory of emanations and
pores (Empedocles, &c.), while his conception of a vibratile move-
‘ment imparted to the actualised “ diaphanous” may, perhaps, be
regarded as a partial anticipation of the modern doctrine of a
luminiferous ether. We cannot, however, push this comparison
very far, since he maintained, in opposition to Empedocles, that
light does not travel. It is not, I think, necessary to summarise
the Aristotelian teaching in so far as it deals with structure,
since, for the reasons already mentioned, it is of purely anti-
quarian interest. The curious reader will find ample material, if
he desires to pursue the matter further, in the works cited by
Professor Beare.

We can now consider for a moment the relations subsisting
between Greek doctrines and the modern development of visual
physiology and psychology.

The reader will have noticed already that the opinions I have
summarised are concerned both with the theory of visual sensations
proper, and the nature and functions of the eye itself. Or, roughly,
they are, in the modern terminology, partly psycho-physiological
and partly anatomical or histological.

Subsequent progress in these two departments has not been
equal. Thus, while we are less ignorant than the Greeks regarding
the structure of the eye and have framed formule more accurately
descriptive of physical concepts, the development of physiological
psychology has not been so great and is largely the work of recent
times. The result has been that our present way of looking at and
thinking about the structure of the eye and the physical changes
associated with colour vision owes comparatively little to the
Greeks, and may be said to date from the epoch-making discoveries
of Newton. Theories of colour sensations, on the other hand,

: 2B

:

may be traced through Hering to Goethe, and the latter almost
explicitly founded his work on that of Aristotle. |

It is true that the study of visual psychology received a consider-
able impetus at the beginning of the eighteenth century from the
work of Berkeley. But Berkeley’s writings are perhaps rather a
contribution to epistemology than to physiological -psychology as
we now understand it.t

I shall therefore. pass to the development of our knowledge as
to the actual process of stimulation, so far as experiment has
tended to display it, and the theoretical developments this has
received in modern times. We can then again take up the thread
of the narrative treating of visual sensations and attempt an
estimate of its modern outcome. Before leaving this pre-
liminary sketch, however, it is well to point out one difficulty
in framing an hypothesis of vision, which hampered the acutest
thinker of the Greek period, but from which we have partially
escaped.

It will have been seen that practically all these philosophers
either explicitly or implicitly adopted the postulate that like acts
upon like. Anaxagoras might appear to be an exception, but a
little thought convinces one that the exception is only formal.

In adopting the literal converse of the proposition he too is com-
mitted to the belief that there is some necessary connection in
kind between the processes occurring within the eye—or the mind—
and those supposed to exist outside of it. This idea pervades all
the Greek speculations—thus, since the external medium is trans-
parent, there must be some internal transparency ; since “ fire ”
is visible, there must be some internal “fire” by which it is
perceived, and so forth. In fact this “similarity hypothesis ”
~ might be regarded as the most primitive of all forms of specula-
tion. There is reason to believe that sympathetic or homeopathic
magic, an obvious extension of the same idea, is culturally older
than any religions, while most of the latter embody the conception
in some more or less changed form.

The real importance of what is called Miiller’s Law of Spétific
Sense Energy, is that it contains an explicit denial of any necessary _

386 STUDIES IN SPECIAL SENSE PHYSIOLOGY

1 For Berkeley’s views on colour, see ‘‘The First Dialogue between Hylas and —
Philonous”’ (vol. i., p. 314 e¢ seg.) ‘‘ Alciphoron,” Fourth Dialogue (vol. ii. —
p 288, &c.). Cf. also ‘‘ An Essay towards a\New Theory of Vision” (vol. i p. 79
et seg.). The references are to Sampson’s octien (Bell, 1898).

STUDIES IN SPECIAL SENSE PHYSIOLOGY 387

qualitative connection or resemblance between the physical pro-
cesses of stimulation and the psycho-physiological changes asso-
ciated therewith in the sense organ and “consciousness.” For
this reason, and although no definite proof of its applicability to
all cases of sensory stimulation has been furnished, the law marked
an important. step forward in the study of physiological psychology.

Section II.—NorMau Visuaut STIMULI

The physical basis of experimental work on colour stimulation
is to be found in the conception of a simple or homogeneous light,
and dates from Newton’s researches in prismatic analysis. By
homogeneous light we understand ethereal vibrations all having
the same wave length or vibration frequency (within assigned
limits). Prisms and gratings allow us to filter such lights from a
mixture and employ them for our experiments. A pure light is
uniquely defined by its wave length, and any such light may possess
any intensity. Unfortunately, the physical unit of intensity is not
readily fixed.

In any spectrum, the intensities of individual lights depend on
the source of illumination and the method of analysis—z.e. on the
extent of surface over which light of a given wave length is dis-
persed. In an interference spectrum, dispersion is uniform; in a
prismatic spectrum, on the other hand, it increases from red to
violet, so that the short-waved light is relatively less intense than
the long-waved. Spectra obtained by the two methods are not
therefore directly comparable.

By colour or light mixing we understand an arrangement by
means of which two or more homogeneous lights fall upon the
same retinal area. Numerous experimental methods have been
devised for this purpose, and the results obtained ? enable us to
formulate certain general statements respecting chromatic stimuli.

1 The application by Krarup (H. Krarup, Physisch- opthalmologische Grenz-
Leipzig, 1906) of Angstrém’s energy measurements is a step in the
right direction.

+ As this essay is chiefly concerned with the theories of colour vision, I assume
the reader to be acquainted with the main experimental data and methods. Such
knowledge can be obtained by consulting any good text-book, for instance Dr.
Rivers’ article in the second volume of Schiifer’s Text-book, or Prof. v. Kries’ article

in the third volume of Nagel’s Handbuch,

388 STUDIES IN SPECIAL SENSE PHYSIOLOGY

These statements owe their present form to Grassmann, and can
be summarised in the following way :—

1. If in a mixture one component be continuously varied, the
appearance of the mixture will likewise vary ; unequal lights mixed
with equal lights produce unequal mixtures.

2. On the other hand, lights which appear equal give, when
mixed, equal mixtures. A corollary is that proportional increase
of the intensity of each component does not destroy a match.

Passing to the actual observations, we at once note that the
effect of mixing spectral extremes is the production of a colour,
purple, not present in the spectrum at all. It thus follows that
any graphical representation of our results must take the form of a
closed curve, since, passing from red to violet, we can either travel
over the range of spectral colours or by way of purple.

If we mix lights not belonging to the extreme ends of the range
our results are quite different. The simplest cases are those of
mixing colours of wave length not less than 540 uu. For instance,
a red (670 wm) mixed with a yellow (580 uu) gives a pure colour
of intermediate wave length; the greater the proportion of the
long wave-lengthened component in the mixture, the nearer will the
position of the mixed colour be to the red end, and convetsely.?
The mixing relations for this part of the spectrum are therefore
straightforward ; but the results obtained—i.e. that two simple
lights when mixed give a colour matching that of a simple
light the wave length of which is intermediate between those of
its components—are only valid for a small part of the range. If
we mix a blue-green (510 uu) with a blue (460 uu), the mixture,
although resembling, perhaps closely, a pure intermediate, e.g.
_ 490 up, does not match it perfectly. The mixed colour is paler,
or as we say, “less saturated,” than any of the spectral colours.
This is still more evident when we choose our components in such
a fashion that the wave length of one is greater and that of the
other less than 517 wu. If one constituent is taken a little nearer
the red than 560 wm and the other diminished, in wave length,
in each experiment, then, with suitable proportions, the mixtures
pass from greenish yellow becoming paler and paler until we reach

1 It is very important to remember that when we say that two colours are
‘‘equal” or “match,” we only mean that viewed under apparently the same
conditions they look alike, i.e. are followed by the same results in consciousness.
Neglect of this truism has been a fertile source of misunderstanding.

STUDIES IN SPECIAL SENSE PHYSIOLOGY 389

a combination which corresponds to a sensation of whiteness. As
we tend to assign a unique position to white in our scale of
sensations, it is customary to complete the mixing laws by the
following addition :—

3. Any light mixture whatever can be matched by a mixture of
a définite homogeneous light (or a definite purple) and white light.
That our results may be as general as possible, it is well to note
that there is no necessity to accord a special place to white,
although it is convenient in practice.

We see then that the mixing experiments give us variations in
colour tone and variations in whiteness, that is, two variables, so

that our results ought to be expressible graphically by some plane

figure. We have also seen that we can pass from red to violet
through the spectral colours and back again to red through purple,
so that our graph should be a closed figure. Finally in virtue of
the fact that the position of any mixed colour depends directly
upon the relative proportions of its components, we infer that the
method of determining the position of the centre of inertia of
masses might be adapted to the task of ascertaining the position
of a mixed colour, given the nature and proportions of its
constituents.

If three colours, A, B, C, none of which can be mixed from the
other two, be represented by three points in a plane, then, on
assigning to them values in terms of any unit, the situations and
quantitative values of their mixtures can be ascertained. Thus a
colour mixed from a units of A and b units of B will lie on the
line A B at the point at which the centre of gravity of two masses
aA and bB (representing the proportions of each colour in the
mixture) would be situated.

In order to establish the correctness of this method it is

necessary to prove that, given the experimental laws of colour-

mixing, as above defined, this construction is valid in all possible
cases—i.e. that the situation of a mixed colour, in a diagram,
coincides with that of the centre of gravity of two equivalent
masses when—({1) The two constituents can be mixed from the
three chosen colours; (2) when one can and one cannot so be
mixed ; (3) when neither can so be mixed.

The proof is too long for insertion in this essay, but it is quite
straightforward (*). We can show that the co-ordinates of the point

= 1 Cf. on this point, J. v. Kries, Nagel’s Handb., vol. iii., p. 116.

390 STUDIES IN SPECIAL SENSE PHYSIOLOGY

at which the mixture must be situated according to the mixing
laws, are the co-ordinates of the centre of gravity of masses |
situated at the points at which the components are represented.

It is clear that a diagram constructed on these principles will
vary in accordance with our choice of units and fixed points. Thus
Newton chose white as a fixed point and arranged the simple
colours at equal distances from it, so that his diagram was a
circle. We should obtain this result except that the part of the
curve passing from violet to red must be a straight line, since purple
can only be mixed from these colours and therefore lies on the
chord joining them,

Recurring to the experimental facts previously mentioned, we

Green

a

Fic. 4.—Colour Table.

see that the most convenient form of diagram will be that
figured (Fig. 4). From red to yellow the curve is a straight line
since we found that mixtures of colours between these limits
- matched pure spectral lights; we then get a sharp bend in the
part of the diagram beyond green, representing the low saturation
of mixtures from this region; finally we have the straight line
through purple.

Suppose now we select three colours in the spectral series,
e.g. red, green, blue, then in accordance with our previous de-
ductions, all mixtures of these are represented in the triangle
RGB. This includes a good deal of our complete diagram, but
not all of it. If we choose, instead of blue, violet, then the ©
triangle RGV comprises nearly the whole spectral diagram; in
other words, nearly all colours can be matched by mixing three
chosen lights in suitable proportions (vid. infra, p. 404). There is

STUDIES IN SPECIAL SENSE PHYSIOLOGY 391

not, indeed, a complete super-position, because of the bend in
the spectral diagram between green and blue, which means that
mixtures of green and violet are less saturated than spectral
cyanide blue; we can, however, generalise a little.

If spectral greenish-blue be mixed with red in certain propor-
tions, it matches a mixture of green and violet-—

a.G Bl. +b.R.=c.Gr. +d.V.

Hence
a.G Bl. =c.Gr.+d.V. —b.R.

or we have the unmixable colour in terms of our three chosen

colours.

It is to be remarked that colour equations, as they are termed,
of the form
a.R.+b.Gr. Cc.V.=d.R.

seem to be a justifiable way of expressing the facts. Addition is
uniform, the same result being always obtained when the same
quantities are summed; it is commutative, the order of opera-
tions does not affect the result ; it is associative and homogeneous.
Analogies may be discerned in the process of colour mixing.
Green + (mixed with) Red + Violet = Red + Green + Violet = (Red
+ Violet) + Green.

If we define subtraction in terms of arithmetical quantity, as
uniform, non-commutative, and non-associative, similar analogies
can be observed. This, however, is of little importance; the
justification of using the symbol of addition in an arithmetical —
sense is sufficient for our purposes.

We can now consider some experimental points. Since practi-
cally all chromatic stimuli may be expressed in terms of three,
researches can be planned in the following way. A definite
spectrum, e.g. the prismatic spectrum of an Auer gas lamp, and
three lights of arbitrary but constant intensity, e.g. a red, a green,
and a violet, are selected; each part of the spectrum is then
matched by a mixture of all the three or of two, or by only one
of them. In this way, Koenig and Dieterici investigated normal
colour vision (1°). Details of the results need not detain us; all I
wish to emphasise here is the general conclusion that the experi-
mental facts of colour stimulation can be graphically represented
by a plane figure and the possible forms of stimuli reduced to

392 STUDIES IN SPECIAL SENSE PHYSIOLOGY

terms of three independent variables; that is to say, from the
point of view of stimulations, normal colour vision is trichromatic.
It is important to notice that a choice of variables is, from the
theoretical standpoint, arbitrary ; indeed, if a table be constructed
in terms of three primaries, A’, B’, C’, a second can be deduced
in terms of another three, A”, B’, C’, because, in view of what
has been said, we can evidently define any one of the new
variables, e.g. A”, in terms of the old ones by a linear relation of |

the form
A” =a.A’+b.B’+c.C’.

The process, in fact, merely involves a change of the co-ordinate
axes. Of course, if we choose the three primaries so close together
that we cannot experimentally reproduce all the spectral stimulus -
values, our table will involve negative directions, but this is of no
theoretical importance.

Summarising the points dealt with in the last few pages, we
find that—

(1) Fixing our attention on stimuli alone, mixing results are
functions of two variables and graphically expressible by means of
a plane figure. .

(2) Colour differences can be expressed in terms of three chosen
stimuli, the choice being theoretically unrestricted, but in practice
certain real stimuli are selected for convenience. |

I must reiterate here the fact that all these statements purport .
to be merely descriptive and to resume experimental observations |
as briefly as possible. Colour diagrams and the assertion that
colour vision is trichromatic are only short ways of expressing
experimental results; they contain no hidden theoretical assump-

“tions, and their truth, or falsehood, is purely a matter of observa-
tion and necessary inference from such observations. It is essential
to separate the theory I propose to discuss from the data which
have given birth to it.

Sreotion II{.—ParriaL CoLoUR-BLINDNESS

We have seen that, from the purely experimental point of
view, the characteristics of normal colour vision admit of relatively
simple arrangement, that in fact all the results of stimulation can
be expressed in terms of three different stimuli and no more; we —

STUDIES IN SPECIAL SENSE PHYSIOLOGY 393

must next consider some types of vision which, although abnormal,
throw light upon the normal mechanism. These are the commoner
forms of congenital partial colour-blindness.

_ The existence of abnormal colour perception in certain people
has been recognised for more than two centuries (4) ;} but John
Dalton, the great chemist, was the first who attracted much
attention to the subject (1).

Goethe in his Farbenlehre, which appeared in 1812, gives the ¢.4\°

following description : (1*)—

“* We will here first advert to a very remarkable state in which
the vision of many persons is found to be. As it presents a
deviation from the ordinary mode of seeing colours, it might fairly
be classed under morbid impressions ; but as it is consistent with
itself, as it often occurs, may extend to many members of a family
and probably does not admit of cure, we may consider it as bor-
dering only on the nosological cases and therefore place it first.

“T was acquainted with two individuals not more than twenty
years of age, who were thus affected. . . . They agreed with the
rest of the world in denominating white, black, and grey in the
usual manner. . . . They appeared to see yellow, red-yellow, and
yellow-red like others. . . . But now a striking difference presented
itself. If the carmine were passed thinly over the white saucer,
they would compare the light colour thus produced to the colour of
the sky and call it blue. If-a rose were shown them beside it,
they would in like manner call it blue; and in all the trials that
were made, it appeared that they could not distinguish light blue
from rose colour. ; .

“They confounded rose colour, blue, and violet on all occa-
sions; these colours only appeared to them to be distinguished
from each other by delicate shades of lighter, darker, intenser, or
fainter appearance.

_ “ Again they could not distinguish green from dark orange,
nor, more especially, from a red-brown.

“Tf any one accidentally conversing with these individuals,
happened to question them about surrounding objects, their answers
occasioned the greatest perplexity, and the interrogator began to
fancy his own wits were out of order. With some method we
may, however, approach to a nearer knowledge of the law of this
deviation from the general law.

“ These persons, as may be gathered from what has been stated,

394 STUDIES IN SPECIAL SENSE PHYSIOLOGY ;

saw fewer colours than other people : hence arose the confusion of
different colours. . . .”

Since the time of Goethe a great deal of attention has been
devoted to the subject and its literature has attained to formidable
proportions. I only propose to consider that aspect of the subject
which seems to be of theoretical interest.

The most obvious distinction between the vision of partial
colour-blinds and our own is their inability to perceive differences
which are plain to us. As Goethe says, they see fewer colours
than we do. This difficulty is of special interest because it is
something definite ; it is easy to find out whether a person can
distinguish between the effect produced on him by two stimuli
which certainly affect us differently, while what the actual nature
of the effect is, remains unknown. How, e.g., a certain green light .
affects a colour-blind eye, by what sensation it is followed, we can
only guess ; but we know that the effect cannot be distinguished
by the subject from that produced by a certain physical intensity
of red light.

We have thus to deal with a condition in which the conscious
responses to varied physical stimuli are fewer than in normal
persons; the question is whether experimental results can be
summarised in the simple manner that was possible in the case of
normal vision. It will be found that the results appear capable of
even simpler description.

We concluded that, for most experimental purposes, normal
colour stimulation is expressible in terms of three colours; the
vision of partial colour-blinds is expressible in terms of two only.
If we choose as our fixed lights a red and a blue, these, mixed in
suitable proportions, match any part of the spectrum, as the latter
appears to the partially colour-blind, and a mixture of the two
also matches unanalysed daylight. In the sense in which normal
colour vision is\trichromatic, this form is dichromatic.

But, just as in normal persons the actual proportions of the
constituents in mixtures equal to various spectral lights do not
agree completely, we also find different types of dichromatic vision,
distinguished by their respective mixing ratios. The two classes

1 The question of so-called abnormal trichromatic systems cannot be discussed
here. Consult Koenig, Zeits. f. phys. und psych. d. Sinnes., vol. 4, p. 317. Donders,
Arch. f. Anat. u. Phys. (Physiol. Abth.), 1884, p. 518. Vv. Kries, Zeits. 7. Psy. Ue
Physiol. d. Sinnesorg., vol. 19, p. 63. -

fet

Proportions of Standard Red and Blue in a Mixture of apparently the same Tint as
various Spectral Colours in four cases of Partial Colour Blindness (v. Kries).

ng pee ad tig Deuteranope (1). | Deuteranope (2). | Protanope (1). Protanope (2).
millionths of a
millim. Red. Blue. Red. Blue, Red. Blue. Red. Blue.
670°8 330 | ... 344). 53| ... 49
656-0 Mey 1) BOE) 91) |. 84
642-0 790 | ... 950. 19-0)... 18-0
628-0 1070| ... |1260 ... 38:0 | ... 385
615-0 1470| ... | 1380) ... 63:0) ... | 63-0
603-0 1510} ... | 1550)... 900... 84-0
591-0 1370] ... | 1440) ... | 1000! ... | 1050
5810 1240| ... |1290 ... | 1110 |... | 1130
5710 | 1030] ... | 1080| ... | 1200] ... | 126-0
561-0 820 |... 890 ... | 1080. ... | 1060
552-0 640 |... 650... (20)... | 1010
544°0 520 |... 560... 78:0 | ... 85°0
536-0 410| 63 | 374, 60 | 650] ... 67:5
525°0 26:0 | 12:0 | 21:0 103 | 383) 110 | 468] ...
515-0 15°0| 28:0 | 137 21:6 | 206| 340 | 328] 13-0
505°0 7-7| 360 75 | 32:2 98/350 | 17:2] 29°0
496°0 37 | 48-0 41 463 48| 470 | 84/ 33:0
488-0 16 | 62:0 19 | 58-0 2:2 | 57:0 53 | 49-0
480°0 0-9 | 64:0 0-9 | 67-0 09 | 660 | 29)| 71:0
469°0 03 | 700 03 656 03 | 670 | 10) 69-0
| 460°8 | 67:0 686 .. | 540 | ... | 660
= Fic. 5
z =
150
ro TINA
35 JAmNE
130} 7 ‘
a3 120 \
n0
ny
24 /) N
. fi f ALK
” H \ IN
3 5 ‘a X
=. / N
Ss ~
= ~ &
10 44 SSO = a=
2 BET SS
©12345678 IWN RB HS 6 11 819 2A
— = SF a =
PSSPHSSPR RESTS # = $2? 8
Wave Lengths of Spectrum.

\)

396 STUDIES IN SPECIAL SENSE PHYSIOLOGY

Amounts of Red (Lithiwm Line) required to match a Standard Yellow
(Sodium Line) by 11 Protanopes and 9 Deuteranopes (v. Kries).

Protanopes. Deuteranopes. |
| 214-0 | 8652
213-0 36°3 !
211°0 36°31!
205°0 36°5?
1960 38°4
198-0 373 |
210°0 37:0 |
| 200-0 37'0
210°0 37'8
203-0 37°0 |
225°0 369
| a 38:0

Ratio is 5: 1 (Approx.).

which have been most studied are known as Protanopes and
Deuteranopes. Their special characters will be described briefly.

Experimentally, we proceed as in the examination of normal
colour vision. A certain red and a certain blue are chosen; the
whole spectrum matched and expressed in terms of the standard
lights. The tables and diagram (p. 395) embody the results
obtained by J. v. Kries (#4).

An examination of the curves shows that the cases fall into
two groups in respect of red values. The four sets of blue values,
on the other hand, are not very dissimilar ; in fact, remembering
that the physical differences of macular absorption would be most
influential in that region of the spectrum where the blue values
agree worst, we may regard the similarity as fairly close.

Referring to the tables, we see that for matching spectral
lights of wave length greater than 530 wu no blue at all is
necessary, so that the forms of the red curves beyond this point
are especially instructive. In one group the curve rises fairly
sharply to a maximum in the neighbourhood of 571 up, and then
falls sharply, suggesting a relatively low stimulus value for long-
waved light ; in the other group the rise is more gradual, attaining
* a maximum at 603 wu, while the curve does not fall to so low
a point at the red end.

1 One subject.

STUDIES IN SPECIAL SENSE PHYSIOLOGY 397

Hence, within the region under examination, we may say with
fair accuracy, that the four subjects are grouped into a pair
relatively more sensitive to short-waved light and a pair relatively
more sensitive to long-waved light. The former are called prota-
nopes, the latter deuteranopes.

But we have thus far only examined four cases, and must see
if the results can be substantiated with the help of a larger number
of subjects. If the conclusions just stated be valid, in matching
yellow some partial colour-blinds will require enormously more
red than others (protanopes) ; and this experiment, which can be
readily performed, will test our conclusions. V. Kries made the
test on twenty cases, using red (lithium line) and a fixed yellow
(sodium line). As will be seen from the table (p. 396) the subjects
do in fact fall into groups, one set (protanopes) requiring approxi-
mately five times as much red as the other class (deuteranopes)
to match the standard yellow. The classification is therefore a
tolerably definite one.

This relative insensibility to long-waved light explains the
observation that in protanopes—who correspond to the class badly
named “Red Blinds”—the red end of the spectrum appears
shortened. The shortening is, however, of little interest from our
present standpoint.

It is to be remarked that individual differences occur within
each class. In the two protanopic cases, from 552 uu onwards
to violet, one subject constantly demanded more red in his mixture
than the other. The subject requiring less red may be presumed
to have a deeply pigmented macula, so that thé homogeneous light
was weakened by selective absorption, because the diminution in
red values agrees with the known increments of absorption as we
pass towards the violet. The difference is of some importance in
connection with an interesting peculiarity of dichromatic vision.
Since daylight can be matched, for the dichromatic eye, by a
mixture of red and blue, and since all spectral colours can be
matched by mixing these standards, we should expect some spectral
colour to match more or less closely unanalysed daylight. . The
situation of such a colour is called the “ Neutral Point” of the
spectrum. As for protanopes the stimulus value of lights falls off
rapidly towards the red, their neutral point should be nearer the
violet than that of deuteranopes, and this is generally the case.
But, if there is a good deal of macular pigmentation, the mixed

398 STUDIES IN SPECIAL SENSE PHYSIOLOGY
light undergoes selective absorption, and the homogeneous match
is nearer the red end. Thus the typical difference may be oblite-
rated and a simple determination of the neutral point would not
enable us to distinguish the two forms.

A study of the neutral point, however, immediately brings to
our notice that characteristic which has attracted the attention of
practical men. Spectral light between 490 and 500 uu induces
normally the sensation green; for the dichromatic it has the
same effect as unanalysed daylight or a mixture of red and blue.
Now this mixture contains much red and little blue, so that a 7
normal person asked to name the simple colour and the mixed .
colour which look alike to the dichromatic would probably call
them green and red; so that we can say that both protanopes
and deuteranopes confound red with green. Even here we observe
a class difference. In matching a given bluish-green, the prota-
nope, being relative insensitive to long waves, requires much red
in the red-blue mixture; the deuteranope takes about the same
amount of blue but much less red. Accordingly, a protanope will
match a light bluish red (physically speaking) with a green that
appears to us much darker, eg. a scarlet with olive green; a
deuteranope matches a far bluer red with a green which we should
take to be about equally bright. Hence, although both groups
confuse certain reds with certain greens, the matches of one class
are not usually valid for the other.

These then being the chief characteristics of the two common
forms of colour-blindness, we must endeavour to ascertain what
relations their visual systems bear to those of normal persons.
The mere fact that the systems are dichromatic would tell us com-
paratively little; we should indeed conclude that, owing to the
reduction of different stimulus forms, sensations of colour are less
numerous for dichromatics than for ourselves, but they might
be quite different, and what we seek is a relation between
stimuli. .

As early as 1837, Seebeck expressed the opinion that two lights
or mixtures of lights which appeared equal to the normal eye,
never appeared unequal when examined by a partial colour-blind.
If this be true, it is of importance, because it would show that
these people lack something possessed by a normal person, but —
have nothing, no stimulus reaction, which is not shared by the
normal eye; in other words, colour-blindness is purely an error of

nt

STUDIES IN SPECIAL SENSE PHYSIOLOGY 399

defect not excess. The validity of normal equations for the two
groups of partial colour-blindness has been recently tested by
v. Kries. His conclusions are clearly expressed in the following

“One employs the frequently cited equations between a homo-
geneous yellow and a mixture of red and yellowish-green (670°8 and
550 uu). As all lights in this region are of equal stimulus value
for the colour-blind, whatever be the ratio of red : yellowish-green,
one can always give the homogeneous yellow an intensity such
that the match is good either for a protanope or a deuteranope,
but in general the matches of the one are not valid for the other.
_ As we should expect, a strongly red mixture is for the protanope
equivalent to a yellow of relatively feeble intensity ; a deuteranope
finds in a match arranged by the protanope, the mixture too
bright and the pure yellow too dark. The relation is reversed for
strongly green mixtures. With extraordinary accuracy, however,
we find that for the ratio of red : yellowish-green that has for the
trichromatic an equal colour tone with the homogeneous yellow,
both groups agree; trichromatic equations are valid for both
protanopes and deuteranopes. Conversely, if we try to find an
equation valid for both groups, we arrive precisely at the one
valid for a normal person.” }

Additional evidence is afforded by the following considerations.
Suppose we prepare a table giving the mixing ratios for a normal
person in matching spectral colours between 670°8 wu and 550 uu.
The results are as follows :—

Spectral Region. Proportions of Standard Colours.
Wave Length. 670°8 pp. 552 wp.
670'8 88°5 oe
628-0 251-0 10
6150 276°0 27
603°0 270°0 49
591-0 | 202-0 67
581-0 123°0 76
571-0 | 73°0 91
561-0 21-0 80
552-0 | aay 71

1 Nagel’s Handb., vol. iii. p. 160.

er'er
*

400 STUDIES IN SPECIAL SENSE PHYSIOLOGY —

We also find that a certain deuteranope requires 33 units of the
standard 670°8 to match the spectral 670°8, and 64 units of the
same standard to match the spectral 552.

If deuteranopic vision be merely a reduction form, we ought to
be able to calculate from these data the stimulus values of the
intervening lights. Take as an example 591, which is matched
by 202 units of 670°8 plus 67 units of 552. We must change from
the arbitrary units of the normal system by dividing by 88°5
and 71 respectively, and then express in the deuteranope’s intensity
system by multiplying by 33 and 64. The stimulus value should
be therefore : 202 x 33 + 88:5 + 67 x 64 -- 71 = 135 (approx.) units.

This, then, is the stimulus value of 591 wm expressed in terms
of the intensity values of 670°8 and 552 wu on the hypothesis
that a match good for a trichromatic eye is valid for a dichromatic.
The observed value was 137. In this way the following table was
obtained : (!5)—

Stimulus Values for Deuteranope and Protanope.

Deuteranope. | Protanope.
Wave — ee eee ee ere eee
Length.
Calculated. Observed. Calculated. Observed.
|
670 83 33 | 4:9 49
628 106 107 | 28'8 38°5
615 126 145 | 54°2 63°0
603 145 151 86:0 84:0
591 135 137 108-0 105°0
581 114 124 | 117°0 113-0
571 110 103 137°0, 126°0
561 76 82 | 1110 106°0
552 64 64 | 101°0 1010
|

A further, but less satisfactory test is afforded by the con-
struction of a colour diagram or “ triangle” combining observa-
tions made upon the two classes of colour-blinds. As this would
involve the discussion of some rather technical details, and involves
certain assumptions of questionable validity, it will not be further
considered in this essay.*

1 See the memoir by v. Kries citel in the last footnote, also Nagel’s Handb., —
vol. iii, p. 162, and especially for the theory of a dichromatic ‘‘Fehlpunkt,” —
Helmholtz, op. cit., pp. 363, &c. I am deeply indebted to Professor v. Kries for
information respecting his work on dichromatic systems.

\ .

b
|

STUDIES IN SPECIAL SENSE PHYSIOLOGY 401

Summing up this rather difficult piece of work, I think the
reader will agree that :—

(1) The two commoner forms of partial colour-blindness are
distinguished one from another by a different responsiveness to
stimulation by long and medium wave-lengthened light. Protanopes
are relatively insensitive to long waves, deuteranopes to moderately
long waves.

(2) Each is an example of dichromatic vision, using the term
in a purely experimental sense.

(3) Each may be regarded as, to some extent, a reduction form
of normal vision, although, as we shall see later, this conclusion
cannot be pushed very far.

The forms of partial colour-blindness just described are of
everyday occurrence, and their recognition of obvious practical
importance ;' another type less common, and therefore less com-
pletely studied, is that known as blue or blue-yellow blindness.
This condition, unlike the last two, is not as a rule congenital,
usually one-sided, and associated with definite pathological changes
in the retina; it affects, generally, only a portion of the visual
field. Koenig’s observations make it probable that this type also
is dichromatic ;* two suitably chosen lights will match the entire

1 For the practical tests employed in the detection of colour-blindness, the
reader must consult the special treatises. It may be remarked that considerable
difference of opinion exists among ophthalmologists as to the reliability of the test
in common use.

2 For the reader’s convenience, I give a list of the chief papers dealing with
blue-yellow blindness. :

(1) J. Stilling, Beitrige : z. Lehre vy. den Farbenempfindungen Klinische
Monatsbl. f. Augenheilk. Jahrg. 13 (1875), 2nd Supp. p. 41, Jahrg. 14, 3rd Supp.
p- 1. Stuttgart, 1875-6.

(2) Cohn, Studien tiber angeborene Farbenblindheit, Breslau, 1879, pp. 139-148
(five cases with good bibliography).

(8) Donders, Annales d’Oculistique, 12th series, vol. 4, 1880, p. 212.

(4) Holmgrén, Centralbl. f. Augenheil., 5th Jahrgang, 1881, p. 476.

(5) Hermann, Ein Beitrag z. Casuistik d. Farbenblindheit. Inaugural Disserta-
tion, Dorpat, 1882. (Not seen.)

(6) V. Vintschgau, Pfliger’s Arch., vol. 48, p. 431. (A full account, without
theoretical bias, of a case in which no pathological changes were observed and a
precis of the observations contained in 1-5.)

(7) V. Vintschgau, Pfl. Arch., vol. 57, p. 191. (Continuation of (6).)

(8) Hering, Pfl. Arch., vol. 57, p. 308. (A study of v. Vintschgau’s case, which
Hering regards as yellow-blue blindness combined with a weak red-green sense.)

(9) Wundt's Philosophische Studien, vol. 8; p. 173, 1892. (Not seen.)

(10) Koenig, Ueber Blaublindheit, Sitzungsbericht. d. Preuss. Akad. d.
Wissenschaft. in Berlin, 29th Juli, 1897, xxxiv. p. 718 (Pathological).

= . 2c

402 STUDIES IN SPECIAL SENSE PHYSIOLOGY

spectrum. The neutral point is in the yellow, between 566 and
570 up.

At the risk of being tedious, I must emphasise the fact that the
truth or falsehood of the foregoing account depends entirely upon
the trustworthiness of the various observations. None of the
statements rely on any hypothesis as to the mode of action of |
the visual elements. .

Section IV.—AFTER-IMAGES : ‘+

Considerations of space make it impossible to discuss, even
in outline, the numerous interesting observations which have
been made upon visual after-images. I will merely, for the |
purpose of reminding the reader of facts with which he’
is doubtless familiar, tabulate the main results of modern .
work. |

(1) The distinction between “ positive ” and “ negative ” after-
images is not absolute but relative, depending on the nature of the
reacting stimulus.

(2) An image-producing or “retuning” stimulus changes the
stimulus value of a “reacting” (subsequently applied) light, but
only in such a way that the sensation response following exposure
to the “reacting” light is increased or diminished quantitatively.
Colour equations do not lose their validity.

(3) The latter statement is true in the case of foveal vision, but

not for peripheral stimulation.
| (4) We do not know the time relations of the retuning process,
nor whether it proceeds uniformly or in pulses.}

ee

(11) Piper, Zeitsch. f. Psy. u. Phys. d. Sinnesorg., vol. 38, p. 155, 1905 (Patho-
logical).

(12) Levy, Arch. f. Opthalmologie, vol. 62, 1906, p. 464.

(13) Collins und Nagel, Zeitsc. f. Psy. u. Phys. d. Sinnesorg., vol. 41, 2nd part,
p« 74, 1906 (Pathological).

(14) Schenck, Pfl. Arch., vol. 118, p. 161, 1907. (This memoir is mainly theo-
retical ; it describes a case, okey er.)

1 For full information, in addition to the treatises of Helmholtz and v. Kries, _
already frequently cited, see v. Tschermak, Uber das Verhéltnis von Gegenfarbe,
Kompensationsfarbe und Kontrastfarbe, Pfl. Arch., 1907, vol. 117, p. 473. G. J.
Burch, Proc. Roy. Soc. (1900), vol. 66, p. 204. Some amusing observations by
Goethe will be found in his Furbenlehre (Eastlake’s translation, p. 953

\

-
,

STUDIES IN SPECIAL SENSE PHYSIOLOGY 403

Secrion V.—THe Turee-CoLtour Hyporuesis or YounG
AS Mopiriep By HELMHOLTz

As we saw, in an earlier section, Newton’s researches demon-
strating the (conceptually) complex nature of white light and the
physical substratum of chromatic stimuli—as co-ordinated by the
undulatory hypothesis—enable us to frame a coherent, if not
necessarily final account of the physical elements involved in
retinal stimulation. On the other hand, the specificity of physio-
logical response, which finds a not quite accurate expression in

‘Miiller’s law, releases us from some of the difficulties attendant

upon the primitive theories of vision, the propounders of which
were hampered by their acceptance of the dogma of physico-
physiological identity.

On so broad a basis, it is of course possible to erect
many, more or less, substantial edifices. In a famous passage,
R. L. Stevenson relates that he once overheard two persons
arguing. ‘What I advance,” said one, “is true.” ‘ Yes,”
replied the other, “but not the whole truth.” “Sir,” was the
retort, “there is no such thing as the whole truth.” It is well
to bear that saying in mind when one considers the theories of
colour vision.

In attempting to arrive at'an adequate interpretation of any
experimental facts, more than one route is generally open. As a
rule, it does not much matter which path we choose so long as we
keep count of any assumptions made and avoid the introduction
of unnecessary steps. Let us start, then, from the experimental
laws of colour mixing, and see where we arrive by following the
most obvious route. We saw that, for most experimental pur-

_ poses, we could say that a sensation “produced by” a colour

stimulus could be matched by a sensation due to a stimulus obtained
by mixing not more than three lights. We saw that these three
lights did not coincide accurately with any spectral colours, but
that, if we admitted negative values into our colour equations, our

_vision could be regarded as definitely trichromatic, even in terms

of known stimuli. In order, however, to avoid this, let us so
choose our stimuli that only positive values of each are employed.
This means that they must be so chosen that the colour table is

404 STUDIES IN SPECIAL SENSE PHYSIOLOGY

circumscribed by the lines joining their representatiye points in a
plane, e.g. :—

g'

Red

Fic. 6.

This is our first assumption, and is little more than a generalisa- '
tion of experimental facts.

Thus far, we have merely asserted that any stimulus, R’, say,
can be expressed by the equation R’=2.R+y.G+z.V, where
x, y, z are positive real quantities. But, our only measure of stimu-
lation equality being corresponding sensation equality, we imply
(and this is our second and most important assumption) that there
is a definite relationship between the physiological excitatory pro-
cesses which lead up, somehow, to sensations, and the stimulus
magnitudes.

This assumption is justified if we can show that it leads to the
formulation of a satisfactory working hypothesis, and if we assume
the simplest relationship consistent with the experimental facts.
What, then, is the simplest relation we can suppose to subsist
between the stimulatory and excitatory processes? Clearly that,
‘just as stimuli may be reduced to terms of three independent
variables, excitatory processes’ are represented by three inde-
pendent variables. Thus, taking our previous example, any
stimulus, R’=2.R +y.G +z.V, then A=f, (2, y, z), B=f, (a, y, 2),
C=f, (x, y, z), and conversely, =F, (A, B, C), y=F, (A, B, C),
z=F, (A, B, C).

These latter expressions may be taken as “elements” or unit
excitatory processes, or any linear functions of them may be so
taken.!

1 The proof of this statement, although simple, requires some knowledge ot

analytical notation, and cannot therefore be reproduced here. See Helmholtz,
Handb. d. Phys. Opt., 2nd edition, pp. 342-3.

STUDIES IN SPECIAL SENSE PHYSIOLOGY 405

The conception is merely that three independent physiological]
processes exist, each of which is defined by an equation connecting
it with the three independent stimulus values which, as we have
seen, determine the effect of any given stimulus.

This statement represents the fundamental part of the hypo-
thesis, first sketched by Thomas Young, and elaborated by
Helmholtz. It is important to distinguish the essentials of the
theory from its subsidiary parts.

The effect produced by any chromatic stimulus is supposed to
depend upon the resultant changes set up in three independent
“* substances,” nothing whatever being postulated with respect to
these substances except that the magnitude of change in each is a
function of, i.e. depends on, the proportions of three independently
variable stimuli in terms of which the given stimulus can be
expressed. Conversely, any given stimulus value is a function
of the independent activities of three visual “substances.” The
nature of the substances, also the exact relation between them and
the stimuli, are left open. For convenience of illustration, Young
and Helmholtz assumed that the activity of each substance was
associated with a single colour sensation, and chose red, green, and
violet as “elementary sensations” from the present standpoint.
“Substance ” A, when stimulated, was supposed to give rise to the
sensation of red ; B, under similar conditions, to that of green ; and
C to that of violet ; in this way the well-known “ valency curves ”
of the text-books were obtained. The advantage of this method
is that the theory seems more definite, but the disadvantage is
entailed that if the illustration proves irreconcilable with facts of
experiment, the reader omits to notice that what is found wanting
is merely an illustration, not the basal theory.

It is especially important to remember that the colour equations
discussed in Section II. do not pretend to describe any direct
relationship between the hypothetical “ substances” and stimulus
magnitudes. .

In precisely the same way, for the sake of illustration, Helm-
holtz suggested the existence somewhere in the retino-cerébral
apparatus of three sets of fibres, each corresponding to one of the
hypothetical substances.

This suggestion was less happy because its utility was not so
great as, and the chance of misunderstanding greater than, in the
previous case. The red, green, and violet fibres have reigned long

406 STUDIES IN SPECIAL SENSE PHYSIOLOGY

and ingloriously over the student’s imagination: it is time to
remember that they are pure abstractions, no more essential to
the theory just sketched than the employment in algebra of the
letter x to denote an unknown quantity is an essential procedure
in that science. To avoid this source of misunderstanding, I shall
use Prof. v. Kries’ term, Components, and speak of the theory as
the “ Three Components Hypothesis.”

Another mistake is illustrated by the following quotation from
a paper by Miss Calkins : (*)—

“From the point of view of a psychological analysis of our
conscious sensations of colour, the postulates of this theory are
not in accordance with the facts of observation ; for, even granting
that violet is a simple fundamental colour sensation (which many
observers regard as complex), it can hardly be denied that yellow .
is just as well characterised and definite a sensation as red or
green. Yellow looks yellow, and does not seem at all like a mixture
of red and green, or indeed any other colour mixture.”

Objections of this type are simply irrelevant. The theory isonly —
an attempt to express physiological processes, of admittedly hypo-
thetical character, in terms of experimental facts ;1 it has nothing.
to do with a psychological analysis of sensations. Whether such
analysis be possible may be doubted ; in any case it is and can be
no part of our present inquiry, which is only concerned with visual
sensations in so far as the latter are signs of the existence of a
physiological reaction.

Having reduced the hypothesis to its simplest terms, let us
apply it to the facts reviewed in the former sections of this article.
Abnormal trichromatic systems are satisfactorily described if we
suppose one of the visual components to be defined in a peculiar
way. Thus, if a component A is normally defined as f, (2, y, 2),
in these cases it is some other function, /, (x, y, 2), say, of the
stimulus values.

Turning to dichromatic systems, we have seen that, from the
experimental standpoint, they are reduction forms of a normal
system. ‘Theoretically considered, the simplest reduction we could
imagine would be the absence or ineffectiveness of one of the three
normal components. Thus, if we take R, G, V (for the sake of
clearness) as the normal components, in the absence of R. all
sensations (sensation being used with the meaning above defined) —

1 i.e. in terms of stimulus values.
o

STUDIES IN SPECIAL SENSE PHYSIOLOGY 407

are functions of G and V, a condition approximating to that of
protanopia. If Gis absent, we get a form resembling deuteranopia.
Under such conditions, not only would the relation between
dichromatics and trichromatics be easily intelligible, but further
we could determine, from observations on dichromatics, the com-.
ponents of a normal system.1 A stimulus inoperative upon a
dichromatic eye must act exclusively upon the missing component.
We have learned how to find the situation of such a stimulus in
the colour diagram (the ‘‘ Fehlpunkt”’), and the two such points
obtained for the two systems of dichromatic vision determine the
stimulus relations of two visual components of a trichromatic eye.
All this depends, however, on the assumption that one com-

ponent is absent and everything else unchanged in a dichromatic

eye. Modern work renders it doubtful whether we may make
this assumption. In 1885, when the second edition of his great
treatise was being prepared, Helmholtz wrote as follows to Lord
Rayleigh : (17) “I have never doubted that our colour system de-
pended on three variables and no more. In regard to colour-
blindness, the recent observations of Donders and of my assistant
Dr. A. Koenig, show that this defect cannot be referred simply to

‘the lack of one of the fundamental colours, but that two of the

primaries (red and green) appear to acquire a more even distribu-
bution in the spectrum, so that now one and now the other makes
a more vigorous impression; in other words, the resulting curve
approximates now more to the red and now to the normal green
sensation. In addition to this we have every shade of lessened
power of discrimination. Consequently different individuals require —
very different mixtures of lithium and thallium light in order to
make up sodium light.”

But if we cannot regard dichromatic vision as differing from
the normal merely in the absence of a component, we can, in
terms of the fundamental hypothesis, assert that it depends upon
a visual system made up of two variables defined by such expres-
sions as & = dp, (A, B, C), and y=, (A ®, C).

This way of looking at the matter is consistent and logical, but
it is not free from objection. Thus we could not deduce from such
an expression any definite statements respecting the components
of normal systems; the interpretation of dichromatic systems is,
necessarily, expressed in such highly general terms as to be hardly
1 Or rather the stimuli which act exclusively upon such components.

408 STUDIES IN SPECIAL SENSE PHYSIOLOGY

capable of direct verification. To put the matter in a nut-shell,
the older conception of partial colour-blindness as due to the
absence of a normal component is simple and, if true, practical,
but is not, in fact, quite adequate; the more general form is
adequate, but not very helpful.

Next, what has the Component Hypothesis to say with regard
to the phenomena of after-images ?

A noteworthy feature of after-image experiments is, of course,
that stimulation with a given light increases responsiveness to its
complementary. It would appear, therefore, easy to imagine that
activity of the three components, or any one or two of them, in
a certain way diminishes their responsiveness in one direction,
increasing it in an opposite direction. This amounts to supposing
that we have a condition comparable with the state of the reflex _
arcs, so brilliantly described by Sherrington: the nervous path is
occupied by one form of motor discharge, and this very occupancy
paves the way for a discharge different, and even opposite in kind.

To so highly general a statement as this, no objection will be
found, but if we investigate details, difficulties arise. For instance,
the apparent saturation of spectral colours is greatly enhanced by
previously stimulating the eye with their complementaries. Helm-
holtz accordingly supposed that all the spectral colours stimulate
each visual component. But, if this be true, the simpler inter-
pretation of colour-blindness once more fails. Observations of
dichromatics suggest that lights having wave-lengths greater than
550 wu do not affect the third component (the “blue” or
“violet” component) at all, because no standard blue had to be
mixed with the standard red in-order to effect a good match. To
a normal eye, however, the saturation of spectral yellow (589 um)
18 unquestionably enhanced by previous exposure to blue. Either
spectral colours do not affect all three components, in which case
the theory does not cover after-image effects, or the simpler
explanation of partial colour-blindness must be abandoned. In
view of what has already been said, the reader will perhaps agree
that the second alternative is the more plausible, and conclude that
after-images are adequately described at the cost of strengthening
our suspicion that dichromatic and trichromatic systems cannot be
co-ordinated in any simple manner.

So far we have found that the Hypothesis of Three Components
describes with sufficient clearness the facts of normal colour vision, —

STUDIES IN SPECIAL SENSE PHYSIOLOGY 409

including the phenomena of after-images; that it also describes
the facts of partial colour-blindness adequately enough, but in
very general terms, the earlier direct explanation being insufficient.
We have now to see whether any experimental evidence can be
found pointing to the existence of independent visual components
satisfying the above conditions, or conceivably capable of satis-
fying them.

Evidence of this kind is furnished by the experimental pro-
duction of a peculiar form of colour-blindness by G. J. Burch. (!%)
This observer exposed his eye to direct sunlight in the focus of
a two-inch lens behind coloured glasses. A gelatine film stained

with magenta and combined with a medium ruby glass was found

to transmit a fairly pure red, three thicknesses of green glass
were used for green, and a tank of cupric ammonia-sulphate for
violet. Similar arrangements were made for the other hues, and
in some experiments a large spectroscope was employed. Two
minutes’ exposure was sufficient to produce the maximal effect in
the case of red.

After exposure to red light, the following effects were noted.
Scarlet geraniums appeared black, calceolarias and sunflowers green,
purple flowers, such as clematis, violet. Pink roses were sky blue.
Fatiguing with violet light caused objects reflecting violet light
to appear black, purples and reds seemed crimson. Green stimu-
lation made the foliage appear reddish or bluish-grey. But, after
these exposures, “the colour by which the eye has been dazzled,
and to which it is now blind, tints all those objects which naturally
reflect none of this.” The truth of this is illustrated by a simple
experiment. (!*) Suppose the eye to be somewhat fatigued by green,
as during a long country walk, if under these circumstances the
eye be directed to a small red spot on a black surface, e.g. a
geranium petal on the black cover of a book, and one walks
quickly with it into a dark shed or barn, the colour of the petal
changes from red through orange and yellow, becoming eventually
perhaps whitish. On coming into the light again the red re-
appears.

These experiments suggest that stimulation with red, green,
and violet alters responsiveness with respect to these stimuli alone,
and the same is found in the case of blue. Orange stimulation,
on the other hand, affects not only the appearance of the orange
but that of the red and green as well. Both positive and negative

410 STUDIES IN SPECIAL SENSE PHYSIOLOGY

effects pass off rapidly in the case of artificial red blindness (in
ten minutes), more slowly after violet fatigue (in two hours).

It is, 1 think, obvious that the state of affairs presented by
these experiments is highly complex. We are dealing with a
change of responsiveness, analogous to the retuning effects, as they
are called, produced in the study of after-images, but of greater
magnitude, and in less simple form. Take the experiment quoted
as to the apparent hue of a geranium petal after green stimula-
tion: this is an ordinary after-image effect, and differs in no way
from the results obtained by other workers; in the case of
exposure to stronger green light, the effect is similar. How does
this, we may ask, differ from the experiment with intense orange
light 2 Simply in the fact that “retuning” with orange, red
and green both act like orange itself in inducing a negative image. —
The conclusion that in this case the mechanism involved in the
production of orange is compounded of a mechanism yielding a
sensation of redness and a mechanism responding with a sensation
of greenness is reasonable, and finds some confirmation in a recent ~
experiment carried out by Burch. (?°)

We know that responsiveness to green is increased, relatively
to that for red stimulation, by resting the eye in darkness ; hence,
if orange or yellow depends upon a fusion of two physiological
processes, one concerned with green, the other with red, then,
under conditions of feeble illumination and dark adaptation, the
yellow should appear greenish, because the mechanism responding
by a sensation of greenness, is more active under these conditions
than that associated in the same way with redness.*

Burch found this actually to be the case ; “the sodium lines
appeared pale green when of the minimum visible intensity.”

These results do therefore support a contention that com-
ponents in the sense of our theory may possibly have a physio-
logical counterpart. I do not think, however, that the view that four
components—a red, a green, a violet, and a blue—exist is proved
by Burch’s experiments. To prove that any light acts upon only
one component it would be necessary to show that after dazzling
with, e.g., blue, any mixed light was altered by the subtraction
of blue, and that any light not containing blue had that colour
added to it. The facts that the condition is transitory, is perhaps

1 The reader must forgive the apparent confusion between object and subject of
vision which is rendered inevitable by the necessity of being concise.’

STUDIES IN SPECIAL SENSE PHYSIOLOGY 4il

attended with some risk, and almost certainly involves psychological
complications, render exact observations difficult. Under the
circumstances, it is perhaps best to say that, although the experi-
ments are perfectly consistent with a component hypothesis of the
type discussed, it would be rash, on the strength of them, to make
any general statement as to the nature of the components from
the physiological standpoint. Theoretically it does not matter
whether we adopt three or four components ; the algebraical form
of our theory would not be changed, but we should lose the
practical advantages of considering normal colour vision to be,
experimentally, trichromatic, which would be a serious objection.

Before finally summarising the case presented, two matters

“need attention. First, as to monochromatic vision or total colour-

blindness. It has been asserted that such a condition cannot be
described in terms of the Young-Helmholtz theory. As a matter
of fact, the assertion is inaccurate ; symbolically we could cover
the facts by supposing that the functions defining the variables
are identical thus: A=f(z, y, z)=B=f(g, y, z)=C=f(z, y, 2),
or, graphically, we can put it that the three valency curves coincide.
In any case, the reader will probably see reason to think that
monochromatic vision depends upon a mechanism entirely distinct
from the precursors of normal foveal vision, and its treatment
should be kept separate from that of the phenomena with which
we are here concerned.

In the second place, no aid has been made to Simul-
taneous Contrast. The reason is that it seems doubtful whether
the phenomena of simultaneous contrast are not of quite a special —
kind. It is true that the original hypothesis of Helmholtz, which
assumed that contrastive effects are dependent upon factors, purely
psychological in nature, can hardly be maintained without some
modification ; the subject is, however, so complex that its dis-
cussion would not be intelligible in the space at our disposal. It
must, however, be said that if subsequent work should compel us
to assign a purely physiological basis to the facts of simultaneous
contrast, it will probably be necessary to modify the theory of
components in such a way that it will become somewhat more
complicated than it is at present.

Leaving this matter for future consideration, we can say that
the Component Hypothesis associated with the names of Young
and Helmholtz supposes—(1) That colour sensations depend upon

‘

i
412 STUDIES IN SPECIAL SENSE PHYSIOLOGY :

the activity of three independent physiological substances of un-
known nature and situation. (2) That the relationship between
these components and the complex of stimuli is expressible
quantitatively by saying that the responsiveness of each component
is measured by a real linear function of three standard stimuli.
(3) The results of stimulating these components are unit sensa-
tions in a purely physiological sense, not units of consciousness.
(4) No spectral light acts upon only one hypothetical component.

The theory describes with sufficient accuracy the main facts,
and there is some direct experimental evidence—that of Burch—
which is consistent with its truth. Further, the main objection
to the hypothesis in its modern form is its highly general nature
and want of direct applicability to the immediate objects of
physiological and physical research. How far this is a real .
objection may be a matter of discussion, but it at least in-
clines one to examine those theories which are, in the colloquial
phrase, less up in the clouds. Such an examination will now
occupy us.

Section VI.—HeErtina’s THEORY OF VISUAL SENSATIONS

In the preceding section, I attempted to trace out the theo-
retical consequences which it seemed possible to reconcile with
the experimental facts of colour mixing. As I have pointed out,
with wearisome frequency, perhaps, the whole process depended
upon the observation that, in general, the effect of a given stimulus
or of a combination of stimuli was constant, so that we might
attribute to the stimulus a causal value. In other words, we have
regarded the sensations as the signs or differentie of stimulation
processes, and our theory, therefore, was in that sense not a theory
of visual sensations at all but a theory of visual stimuli.

If the estimate I formed of the value of this process be at all
just, it would follow that its weakness lay rather in what was
left unsaid than in any incorrectness or improbability in its positive —
teaching. An objector, let us say the hypothetical man in the
street, might perhaps express his criticism in the following terms :
“You compel me,” he might say, “to examine a great many facts,
- and force me to puzzle out some difficult quantitative reasoning, and
at the end you leave me with a few highly general theorems which,
you confess, only describe some of the phenomena. Whenever I —

°

STUDIES IN SPECIAL SENSE PHYSIOLOGY 413

clutched at a straw of definite specific statement, that straw was
instantly snatched away again. Is it worth while going through
so much for so little ? ”

- I do not think such an objection at all unreasonable. It is
good to be as simple as possible, provided we do not sacrifice truth
in the process, and we find that deductions from stimulus values
do not lead us to any very simple results. Let us see, therefore,
what fortune attends us when we pursue our quest by a different
path altogether; perhaps in this way we shall attain to some-
thing more intelligible and practical.

The other line of investigation practically resumes the problem
-at the point at which the Greeks left it, and dates from the
publication in 1810 of Goethe’s Farbenlehre.

The comparatively slight influence that has been exercised by
this work upon the development of modern physiological thought
respecting the nature of visual processes, is due to causes well
worth notice. The physical analysis of white light into mono-
chromatic constituents by Newton had naturally attracted the
chief, almost the exclusive, attention of those who occupied them-
selves with the study of colour vision. Goethe, however, saw
quite clearly that the difficulties of the problem were not to be
overcome by vague references to physical experiments. He saw
that the problem was one of sensations, and he therefore approached
it from a sensational standpoint. Had he contented himself
with this, with an analysis of sensations of colour, his work must
have had an enormous influence; but he went further. The
prevailing tendency to over-estimate the significance of the physi-
cal side of the problem in visual theories led Goethe into the
opposite error. He sustained the thesis that the Newtonian
analysis was physically incorrect, and that the alleged physical
analysis of white light was not in general possible. Consequently,
much of his work is devoted to an attack upon the Newtonian
hypothesis from the physical side. Since this attack failed,
more valuable portions of Goethe’s book became involved in the
discredit this produced.

I can best give an idea cf the valuable parts by quoting a few
significant passages.

“With regard to the German terminology, it has the advan-
tage of possessing four monosyllabic names no longer to be traced
to their origin, viz. yellow (Gelb), blue, red, green. They represent

414 STUDIES IN SPECIAL SENSE PHYSIOLOGY

the most general idea of colour to the imagination, without
reference to any very specific modification. If we were to add
two other qualifying terms to each of these four, as thus—red-
yellow and yellow-red, red-blue and blue-red, yellow-green and
green-yellow, blue-green and green-blue, we should express the
gradations of the chromatic circle with sufficient distinctness ; and
if we were to add the designations of light and dark, and again
define, in some measure, the degree of purity or its opposite by
the monosyllables black, white, grey, brown, we should have a
tolerably sufficient range of expressions to describe the ordinary
appearances presented to us, without troubling ourselves whether
they were produced dynamically or atomically.” (?*)

“Considered in a general point of view, colour is determined
towards one of two sides. It thus presents a contrast which we .
call a polarity, and which we may fitly designate by the expres- —
sions plus and minus.

Plus. Minus.
“ Yellow. ; Blue.
Action. Negation.
Light. Shadow.
Brightness. Darkness.
Force. Weakness.
Warmth. Coldness.
Proximity. Distance.
Repulsion. Attraction.
Affinity with Acids. Affinity with Alkalis.” (2*)

We see here formulated the conception of certain colour sensa-
tions as occupying unique places in our sensational field, and
presenting also, as it were, a species of sensational contrast one
with the other.

Not only is this conception present in the minds of those
who seek to influence us through the colour sense (painters), but
it is given effect to in their practice. |

In a dialogue on colours by Ludovico Dolce, published in 1565,
the following passage occurs : (7%) “He who wishes to combine
colours that are agreeable to the eye, will put grey next dusky
orange, yellow-green next rose colour, blue next orange, dark
purple, black, next dark green, white next black, and white next
flesh colour.” | . .

Titian, according to his biographer Ridolfi, was fond of opposing —

Ld

“a vil: . ——

a

STUDIES IN SPECIAL SENSE PHYSIOLOGY 415
red and blue to his flesh tints, and Rubens contrasted a bright

_ red with his “ still cooler flesh colour” (Eastlake).

The point to mark is the general agreement that certain of our
sensations of colour are really singled out from the whole group
as presenting sharply-defined, special characters. All sensational
theories are primarily concerned with the definition of these char-
acters, and secondarily with an attempt to describe the data in
terms of a physiological hypothesis.

Of such attempts the views developed by Professor Ewald
Hering and his pupils during the last five-and-thirty years are the
most valuable results. Whatever may be our ultimate conclusion
as to the validity of these theories, no one can doubt that they have

greatly advanced our knowledge of visual physiology, and their

study cannot be neglected by any one desirous of acquiring even a
superficial idea of modern conceptions.

According to Hering’s method of analysis our whole visual world
can be resolved into six elementary sensation qualities—white,
black, the toneless, and blue, yellow, green, red, the toned or
bright (bunte) colours.

If we consider the tone-free qualities, we can form a series of
shades or graduations passing from intensest white to deepest
black. If we attend to the toned colours, they can be arranged
in a circle with four divisions.

“Tf we choose in such a colour circle any colour as starting-
point, for instance a red similar to that with which a spectrum
usually begins at the long-waved end, we see the red colours
arranged in one direction gradually becoming more yellowish, while
the redness of the colours correspondingly diminishes, until finally,
passing through orange and golden-yellow, we arrive at a yellow
which contains no trace of the red which is still so apparent in

_ the orange. To this yellow succeed other yellow colours which

play more and more into the green (sulphur-yellow, canary-yellow) ;
further on (as in sap-green) the yellowishness recedes more and

1 In the work of Rembrandt, who is, I believe, regarded by those qualified to
judge as the greatest exponent of contrastive effects, the most striking results seém to
be rather light-dark contrasts, as in the Hague ‘‘ Anatomie,”’ than specific colour
oppositions. For instance, in the (so-called) ‘‘ Nachtwache,”’ the yellow sunlight and
yellow costume of one of the central figures, which produce such a magnificent
brightening effect, are balanced by general shadow without any apparent use of the

” This seems to apply also to the ‘*Staalmeesters.” A careful study
of the chief master-works of painting from the standpoint of the visual physiologist

- Lo Oneeelaiame

»*

- ~~ 5 fl / ie

416 STUDIES IN SPECIAL SENSE PHYSIOLOGY

more behind the steadily increasing greenishness, until we finally
reach a green which seems to be entirely free from’ yellow. To
this succeed green colours which already play into blue (water-
green); further on the bluishness of the colours becomes
increasingly stronger, the greenishness weaker, until we finally
reach a blue exhibiting no more greenishness at all. To this blue
succeed blue colours of increasing reddishness and eorrespondingly
diminishing bluishness (blue-violet, red-violet, purple-red), until
the last trace of bluishness vanishes in a definite red.” (?4)

If we define a pure green as a sensation free from admixture
with blue and yellow, and the other three sensation qualities in
the same manner, we see that our pure colours (from this point
of view) can be arranged in two pairs, yellow and blue forming
one and red and green the other. ‘he members of each pair can
be placed opposite one another in a diagram, because we can only —
pass from yellow to blue or from red to green by traversing the
province of a member of the other pair, as just explained. There
is no pure yellowish-blue or reddish-green sensation quality.

But there is yet another contrast, from the standpoint of sen-
sation quality, between yellow and red on the one hand, blue and
green on the other.

Somehow, in a manner difficult to express in words yet of
universal experience, the two former colours are associated with
a certain heightening and increased vividness of sensation-tone,
while the two latter exercise a depressing or subduing influence.
This finds its expression in the classification by artists of colours
into warm and cold. Goethe has emphasised these points :—

“We find from experience, agajn, that yellow excites a warm
and agreeable impression. Hence in painting it belongs to the
illumined and emphatic side. ‘

“This impression of warmth may be experienced in a very
lively manner if we look at a landscape through a yellow glass,
particularly on a grey winter’s day. The eye is gladdened, the
heart expanded and cheered, a glow seems at once to breathe
towards us.” (75)

Of blue he says: “This colour has a peculiar and almost
indescribable effect on the eye. Asa hue it is powerful, but it is
on the negative side, and in its highest purity is, as it were, a |
stimulating negation. Its appearance then is a kind of contra-
diction between excitement and repose.

iu i

STUDIES IN SPECIAL SENSE PHYSIOLOGY 417

. Rooms which are hung with pure blue appear in some
degree larger, but at the same time empty and cold.

“The appearance of objects seen through a blue glass is gloomy
and melancholy.” (**)

- How far these results depend on mental factors, e.g. an asso-
ciation of ideas, cannot be discussed in this place ; it is sufficient
to recognise their existence.

In the opinion of those whose theories we are examining,
the facts are most satisfactorily described by saying that in
any sensation-complex blue and green produce a darkening,
and yellow or red a brightening effect; the toneless colours,
black and white, also contribute respectively in a negative or

positive sense to the sum total of effects. We have, there-

fore, the brightness of a colour defined in strictly sensational
terms.

We have now arrived at the conception of six primary sensa-
tion qualities arranged in three pairs—white-black, red-green,
yellow-blue. The first member in each case increases, the second
diminishes the subjective intensity or brightness of a sensation-
complex of which it forms part."

“The brightness or darkness of a toned (bunte) colour is,
according to this view, the result of the inherent brightness or
darkness (Higenhell und Eigendunkel) of its constituent pure
colours, which as the pure constituents of that colour agreeably
to their respective distinctness determine the quality of the colour.
In any colour really existent for us is a definite inherent degree
of brightness and darkness, and in accordance -with whether the
brightness or the darkness be the more distinct, we call (the colour)
bright or dark.

“A toned colour may generally be regarded as made up of

_ four primary components, two toned and two tone-free (black and

white). Only in colours of the tone of a pure colour is one toned
constituent present by itself. In any red-yellow colour, e.g. orange,
we have accordingly to distinguish three bright, pure components

_ (red, yellow, white), and one dark (black); but in any green-blue,

three dark (green, blue, black) and one bright. The red-green
and green-yellow colours would contain, however, two bright and
two dark pure components.

_1 Sensation-Complex is a term used merely to indicate the supposed multiplicity

of infra-conscious representatives, not in a perceptual sense.

= ' 2D

7

418 STUDIES IN SPECIAL SENSE PHYSIOLOGY

‘From what has been said the following rules can be deduced :—

“Tf two colours of equal tone and equal purity differ in bright-
ness this is due to a difference in their black-white components.

“Two colours differing in tone may, notwithstanding equal
degrees of purity and equality as regards their black-white com- |
ponents, differ in brightness.

‘With equality of conditions as to the black-white components,

a yellow, a red, or a yellow-red colour is so much the brighter,
a blue, a green, or a blue-green so much the darker, the more
distinct the colour tone in comparison with the black-white con-
stituent.” (77)

This extract describes what is often called the theory of
the “specific brightness” of colours. All that has gone before
purports to be a faithful analysis of our visual sensations without
reference to any hypothesis whatever. That this is a perfectly
legitimate procedure I have already attempted to show: the next
step is to translate these facts, or supposed facts, into terms of
a physiological hypothesis. —

Such a translation can readily be effected.

It is supposed that somewhere in the retino-cerebral apparatus,
in the infra-conscious sphere, four distinct substances exist. Each
of these substances can undergo a building up or anabolic and a q
breaking down or katabolic change. External stimuli will, depend-
ing on their natures, induce either an anabolic or katabolic change
in the substances, and these are associated with a definite colour
sensation. The building up of the black-white substance corre-
sponds to a sensation of blackness, its breaking down to a sensation
of whiteness; anabolism of the red-green substance is associated
with green colouration, its katabolism with red colouration ;
similarly in the third substance yellow is katabolic in origin, blue
anabolic.

Before discussing these views in detail, I should like to clear
up certain popular misunderstandings. Some opponents have
asserted or suggested that the facts upon which the theory is
based differ in some perverse way from those data which are
ordinarily called facts of experiment. This is not the case. The
facts the hypothesis attempts to describe are as legitimately
objects of inquiry as any others within the purview of physiological
science. |

It is further to be noted that the four physiological “sub- —

STUDIES IN SPECIAL SENSE PHYSIOLOGY 419

stances ” have just as much and just as little real existence as the
three components of our other theory. It is idle to say that the
postulated anabolic and katabolic processes are essentially unlike
any chemical mechanisms with which we are acquainted. It is
equally vain to object that stimulation processes in animal nature
are, to all appearance, bound up with katabolic changes; this
would be a valid objection if we tried to identify the hypothetical
substances with any known retino-cerebral constituent. No such
identification is attempted; the suggestion that Hering and his
school identify the black-white substance with visual purple is
altogether false. The fact is that this theory can only be judged

on the grounds of scientific expediency, and in no other way. Does

this method of presenting the facts give us a clearer insight into
the phenomena of vision than the method based upon stimulus
relations? This is the only question which requires to be
answered.

We notice at once that the hypothesis, in the form in which
it has just been epitomised, offers two considerable advantages.
Firstly, it deals with the immediate data of vision, the visual
sensations of colour, directly, and not in terms of stimulation
magnitudes. In this sense it might be called a primary hypo-
thesis. In the second place it is essentially simple and easv of
comprehension, which is a very strong point in its favour.

But if we find, on testing this simple hypothesis with such
facts of experiment as have previously been detailed, that it
rapidly ceases to be simple ; if we find that its apparently direct
grip upon the objects of investigation is perceptibly weakened ; in
one word, if it ceases to be definite, then its characteristic advan-
tages will have disappeared.

Let us first of all attempt to express the facts of successive

. contrast, after-images in terms of the hypothesis. After resting

the eye on a white object, we should expect, under certain con-
ditions, a positive, under others a negative after-effect. The
experimental results agree perfectly with the theory. In the case
of colour stimuli, we can understand why complementary reacting
lights gain in saturation. For example, if the eye be stimulated
with green, anabolism will occur in the red-green substance, an
anabolism which will lead to the formation of a large quantity of
“material.” If now red light stimulates the retina, it produces

not only katabolism of the normal quantity of substance, but the

420 STUDIES IN SPECIAL SENSE PHYSIOLOGY

new formed material also falls to pieces and the correlative
sensation is greatly enhanced. All the simple phenomena of after-
images are adequately described, but a detailed examination yields
less promising results.

V. Kries found that the responsiveness of the eye to mono-
chromatic light was markedly altered by previous exposure to
white. He found that the stimulus value of the red he employed
was diminished in the ratio of about one to four by previous re-
tuning with white.!| How can this come about if the black-white
substance is independent of the red-green substance ?

Hering’s own views on this matter deserve careful study.(?%) He
objects that, in v. Kries’ experiments, the colour used as a reactor
(180° blue, 180° white on a disc) was not sufficiently saturated,
and brings forward the following experiment :—

Two discs are arranged, A and B. A consists of a black centre
surrounded by a white ring, B of a centre composed of 120° blue
and 240° black, encircled by a ring containing 356° blue and 4°
white. A point upon the internal margin of the white ring in A ©
is fixated for a given time, and the experimenter then turns his
eye to an exactly corresponding point in B. Hering always found
that the outer ring in B, under these conditions, looked more
saturated than the centre. |

As the term saturated is not used by Hering in the physical
sense, the exact bearing of his objection to v. Kries’ experiment
is not apparent. Presumably what is meant is that the “ blue-
ness” of such a disc was not distinctly separable from its
‘‘ whiteness,” with the result that the admitted change in the
latter on retuning with white was mistaken for a change in the
former. If this objection is admissible, it is, however, equally
fair to retort that in Hering’s counter-experiment the difference
between the amounts of blue in reacting and comparison fields
was so great that an enormous diminution in responsiveness over
-the retuned area would be necessary for the production of a good
match between the centre and periphery of B. Put briefly, the con-
tention is that after white retuning, a reacting blue and white can
be made to match a pure blue in brightness by adding more white ;
adding more blue will always make the reactor too saturated.
Hering’s experiment does not seem to prove more than that a

1 For an account of v. Kries’ work and some more recent observations of hi
pupils, see Nagel’s Handb., Bad. iii., p. 210, &e. ;

U a a "a 7

STUDIES IN SPECIAL SENSE PHYSIOLOGY 421

diminution of about 66} per cent. in apparent intensity cannot
be attained by retuning with the white he employed. That the
apparent brightness was correspondingly reduced is indeed favour-
able to his hypothesis, but it is to be noted that we have under
these conditions the difficulties of specific brightness comparison
in their most acute form.

The discussion of conflicting experimental methods is, how-
ever, always a thankless and mostly a dull task ; the reader’s special
attention is accordingly directed to the following remarkable
passage with which Hering concludes his memoir :—

“To the change of state experienced by an element of the

‘somatic visual field when acted upon by, e.g. blue light, with which

the blue sensation is associated, the whole somatic visual field reacts
by a change in the opposite direction which corresponds to the
oppositely coloured or yellow sensation, and any light that now
falls on the retina acts, in consequence of this chromatic retuning
of the visual field, as if its yellow valency were increased and its
blue valency correspondingly diminished. This retuning is maximal
in the immediate vicinity of the element acted upon by the blue
light, and diminishes with its distance from the same... . A
white light falling on the neighbourhood of the region which has
been stimulated with blue seems therefore more or less yellowish,
but a white light which falls together with blue on the spot that
has been stimulated with blue, seeing that it behaves as a more
or less yellow-valent light, neutralises the blue valency of the blue
light so much the more, the greater be the quantity of it mixed
with the latter. This explains the striking fact that the chromatic
quality of a saturated colour is so extremely quickly extinguished
by increasing the amount of white mixed with it. . . .”

“When v. Kries, therefore, supposed that, according to the
theory of opposite colours (Gegenfarben), the same result would be
obtained from a fatigued and an unfatigued area if the same
quantity of blue light were allowed to fall on both, but in addition
on the fatigued area a suitably chosen quantity of white light, he
was in error. In such a case, the blue valency of the blue light
at the unfatigued area is unaltered since no other light is mixed
with it; over the fatigued area the blue valency of the blue light
is partly neutralised by the admixture of white. Accordingly the
blue at this latter area must appear less saturated than at the

former. In fact a transitory equality in brightness and saturation

'

422. STUDIES IN SPECIAL SENSE PHYSIOLOGY

between the two areas is only obtained when white is indeed mixed
with blue for the fatigued area, but on the other hand, the blue
light for the unfatigued area is suitably diminished. In general, for
reasons already given, an equality in colour tone for blue can only
be obtained under exceptional circumstances, when the character
of the daylight is specially favourable and the tone of the blue
just right.” (7°)

It has been said by Professor William James that John Stuart
Mill was in the habit of boldly asserting in general terms the
truth of a philosophical theory derived from his father, and then
admitting in detail the validity of all objections to it. A trace of
this method can be discerned in the passage just quoted. The
whole memoir is designed to show that white retuning does not
affect colour valency. Experiments apparently in favour of the’
rival hypothesis are met by other experiments in support of this
contention. We are led to suppose that white retuning and colour
retuning are independent, and naturally infer that since white ~
retuning does not affect colour valency, colour retuning ought not
to affect white valency. This, however, is specifically asserted not
to be the case.

It is not, of course, to be supposed that the two propositions
are logically inconsistent, but the independence of the postulated
physiological processes is no longer paralleled by the facts of
sensational analysis. What is (from the standpoint of sensations)
a pure white has a definite colour valency. Pure white (in terms
of the physiological process in the black-white substance) is just
as hypothetical as anything postulated by the theory of stimuli.

It will, I think, be clear that in order to cover the facts of
retuning, the sensational theory loses some of its original simplicity.
It is interesting to notice that the theory becomes more difficult
to follow by developing in a direction opposite to that followed
by the stimulus theory; the latter became unsatisfactory, to —
some, by tending to be too general, the former by multiplying its
details.

I have enlarged upon the question of retuning, a matter not
perhaps of very special importance in itself, because, as I hope
to have shown, the facts are not quite so easily described by the
Hering theory as some of its supporters would lead one to
imagine. These very facts have been claimed by eager adherents —
of both schools as decisively favouring their respective beliefs.

STUDIES IN SPECIAL SENSE PHYSIOLOGY 423

Perhaps the ingenuous reader will conclude that neither claim
is admissible.

Space and the reader’s patience do not admit of analysing in
detail the further applications of the theory to visual phenomena.
I will merely say a few words on the Hering theory of dichromatic
systems.

It was originally thought that the theory covered these facts
extremely well, and even in so good a text-book as that of Professor
Howell it is suggested that an advantage of the sensational
theory is its better description of the facts of partial colour-blind-
ness. In reality, it seems very difficult to bring the facts into line
with the theory.

It was once suggested that both types, protanopes and
deuteranopes, depended on the non-existence of the red-green
substance, the typical distinction being due to varying degrees
of macular and lens pigmentation, combined with unequal respon-
siveness of the blue-yellow substance.

We have already seen that the characters of the two groups,
protanopes and deuteranopes, cannot be due to differences in
pigmentation, and the inconsistency of the colour equation,
R+G= 652, is difficult to reconcile with this view.

Tschermak, a prominent member of Hering’s school, seems
definitely to abandon this attempt to describe dichromatic vision, (®°)
and, so far as I know, an adequate expression of the facts in terms
of Hering’s hypothesis is not yet forthcoming. This is not a
fatal objection to the theory, because the sensational analysis of
dichromatic vision is extremely difficult, owing to the fact, among
others, that colour nomenclature is adapted to trichromatic vision,
trichromatics forming the large majority of all civilised races. It
must, however, be realised that this hypothesis does not seem likely
to advance our knowledge of colour blindness further than that of
three components.

Our general conclusion, therefore, may perhaps be expressed
in the following terms.

The theory associated with the name of Hering is an attempt
to arrive at a general conception of the visual processes by an
analysis and comparison of sensations. In this way prominence
is given to many interesting facts not specially or adequately
considered by the theory founded on stimulus relations. If,
however, we attempt to build up upon such data an hypothesis

fe wi

424 STUDIES IN SPECIAL SENSE PHYSIOLOGY

adequate to the task of describing all the experimental facts, we
encounter difficulties not less formidable than those we found to
be associated with the Young-Helmholtz theory.

In attempting to meet their respective difficulties, the two
theories become unsatisfactory in different ways. The stimulus
hypothesis becomes too general, the sensational hypothesis too
detailed. Examples have been described in the former’s treat-
ment of dichromatic vision and the latter’s account of after- —
images.

Perhaps the most tempting inference is that these theories are
in a sense complementary—that they both contain some measure
of truth, surveying the vast complex of phenomena from very
different points of view. Neither theory is wholly true nor yet
wholly false ; nor does adhesion to the one imply total rejection ~
of its 3 cusible rival.

I am only too conscious that, like Canning’s clerical friend, in
being brief I have by no means escaped being tedious. My only
excuse, and that but a poor one, is that if we are ever able to pro-
pound a complete theory of the visual processes, this comprehensive
formula will embrace both those I have described, and until that
time comes a critical examination and comparison of both lines
of thought will always be indispensable to those who wish to gain
a real knowledge of visual physiology. In conclusion, the reader
is most earnestly recommended to consult the original memoirs of
Hering and the treatise of Helmholtz dealing with this subject.
He will not, indeed, find them light reading—no really scientific
books ate ; but he will be repaid by a grasp of the matter in hand
such as can never be derived from text-books, however lucid, or
summaries, however long.

BIBLIOGRAPHY

1 Beare, op. cit., p. 18.

2 Aristotle, De Sensu et Sensilibus, Taylor’s Trans., vol. iii., p. 133,
° Beare, op. cit., pp. 36-37,

* Plato, Timeus, Jowett’s Translation, vol. ii., pp. 538-9.

5 Helmholtz, Handb. d. Phys. Optik., 2nd edit., p. 248.

° Plato, Thextetus, Jowett’s Trans., vol. iii., pp. 375, 378.

7 Beare, op. cit., p. 64.

* Beare, op. cit., p. 69.

® Helmholtz, Handb, d. Phys. Opt., pp. 328-330.

STUDIES IN SPECIAL SENSE PHYSIOLOGY 425

” Koenig and Dieterici, Zeits, f. Psy. u. ‘Physiol. d. Sinnesorg., vol.
iv., p. 241.

™ Turberville, Phil. Trans., 1684. Huddart, Phil. Trans., 1777. Whisson,
Phil. Trans., 1778. [Vide Koenig’s Bibliography appended to Helmholtz,
Phy. Opt., 2nd ed., for full bibliography.]

% J. Dalton, Literary and Philosophical Society of Manchester, 1794.

% Goethe, Theory of Colours, translated by Eastlake, London, 1840
(Murray), pp. 45-47.

™ J. v. Kries, Ueber Farbensysteme Zeits. f. Psy. u. Phys. d. Sinnes.,
vol. 13, pp. 241-324 ; and Nagel’s Handb., vol. 3, pp. 153-5. The technic is
partly described in Zeits. f. Psy. u. Physiol. d. Sinnesorg., vol. 12, pp. 4, &e.
® J. v. Kries, Zeits. f. Psy. u. Phys. d. Sinnesorg., vol. 13, p. 241.
© Miss Calkins, Arch. f. Physiologie, Supp. Bd., 1902, pp. 244 et seq.
" Koenigsberger, Life of Helmholtz, Engl. Trans. by Miss Welly, Oxford,

1907, p. 364.

8 G. J. Burch, Phil. Trans., B., vol. 191, pp. 1-34. Proc. Roy. Soe., vol.
66, pp. 216-219.

* Burch, Proc. Roy. Soc., vol. 66, p. 219.

*° Burch, Proc. Roy. Soc., B., 1905, p. 214.

* Goethe, op. cit. (Eastlake’s trans.), pp. 243-4.

*? Goethe, op. cit., p. 276.

*% Tbid., Note C.

* Ewald Hering, Grundziige der Lehre vom Lichtsinn, Leipzig, 1905, &c.
(separate publication not yet complete), p. 41.

*® Goethe, op. cit., p. 307.

*° Thid., p. 310.

*? Hering, op. cit., p. 61.

** Hering, Ueber die von der Farbenempflindlichkeit unabhangige Aende-
rung der Weissempflindlichkeit. Pfl. Arch., vol. 94 (1903), pp. 533, &c.

*® Hering, op. cit., p. 552. ie

%° Tschermak, Ergebn. d. Physiol., lst Jahrg., 1902, Ite Abth., s. 795, &c,

INDEX

ABDOMEN—
Blood determined to, by emotion
and mental work, 148, 149
Blood pressure in, Valsalva’s ex-
periment, 146
Compression of, restoration from
syncope by, 173
Large, production of cerebral
anemia by vertical suspension
of animals with, 173
Abdominal organs, volume of blood
circulation of, recorded by rectal
sound, 148
Abram’s reflex, 186
Acid—
Acetic, properties of, 7
Hippuric, 8
Lactic—
As a cause of fatigue, 254
In muscle, 213
Acids—
Amido—
Basie groups of, 7, 9
Chemical characteristics of,
8
Compounds of protein mole-
cules, 7
Found in muscle, 216
Achromatic threshold of coloured

light, 355; Burch, apparatus for
study of, 357
Adrenalin—

Constricting effect on arteries,
177

Injection of, effect on residual
vascular pressure, 158
Adsorption, examples of, 10
Age, old, and mechanism of respira-
tion, 205 ;
Air—
Alveolar—
Carbon dioxide in, 240
Composition of, and “second
wind,”’ 242
Breathed, total volume of, per
minute, 237
Exposure to, effect on venous
pressure, 130
Sacs, alveoli implanted on walls
of, 185
Spaces, terminal, in lung, 185
Albuminuria, functional, 252
Allorhythmia, induction of, 60, 62

Alveoli implanted on walls of air
sacs, 185

Amido acids. See under Acids

Anemia, 162-5

Anemia, cerebral, production
vertical suspension of animals with
large abdomen, 173

Anesthesia—
Spinal,produced by strain, effects
of, 180
Use of chloroform in, 5
Anesthetics, influence

on nerve
fatigue, 268 »°
Anarthria of Déjérine, 332
Anastomoses following ligation of
arteries, 133
Animals, supra-granular and infra-
granular layers of cortex in, 298
Atrium, terminal air space, 185
Aorta—
Contractility less than that of
carotid, 118
Residual pressure in, compared
with that in vena cava, 157, 159
Aphasia, 318
Aphasia, recent researches in, 330-6
Aqueous, deficient circulation of, in
glaucoma, 141
Arm, volume of blood circulation in,
148
Armlet—
For measurement of arterial
pressure, 121
Readings by, failure in case of
sclerosed arteries, 123, 124
Readings by, obliteration me-
thod compared with readings
by radial hemodynamometer,
124, 125, 126
Use of, 142
Use of, in recording venous
pressure, 128
Arterial origin of active hyperemia,
170
Arterial pulse, primary wave, “c
wave in jugular synchronous with,
102
Arteries—
Blood pressure in—
Constant under alterations
of output from ey 146 —
Effect of exercise and food ©
on, 127, 128 .

“ce ”»

E ae of inhalation of
Fall oh on, 128
how produced, 176,
Disaticedoeas by armlet, 121
— investigations,
12
Raised by excitation of
cortex cerebri, 147
Restoration by constricting
agents, 177
Systolic, variations due to
age, sex, and posture, 126,
12

Cerebral,
139
Contracted and relaxed, differ-
ence between, depends on
muscular element, 119, 121

Contracted and sclerosed, failure
of armlet readings, 123, 124

Contracted, stretching of, 118,
119

Development of, 133

Divided, insertion of lengths of

' transplanted arteries or veins
between, 112

Elasticity and contractility of,
116

Embolism of, 164

Expansion, increase in patho-
logical states, 120

esgr eball, pulsation expansion,

9

Ligation of, results, 133

Maximal pulsation in, 122, 124

Obliteration pressure by armlet
method, 121, 124

Obliteration readings to be taken
during repose, 126

ure in, determined by pos-

ture, 413

Proportion in size and area, 133

_ Relaxation of, permanently pro-
i by freezing and heating,

Relaxed, extension produced by,
first addition of weight, 118

pulsatile expansion,

Blood pressure in, 127
Ramification homonomous,

INDEX

427

Arteries (continued)
Tortuosity of, 120
Transfusion of blood from, to

veins in cases of shock,
179

Union of, with divided ends and
veins, 112

Walls: of, contraction and ex-
ansion of, in tension, 171
peer es, 231, 234
Constriction of, produced ex-
perimentally, 158
Function of, 144
Muscle of, action of pressor and
depressor afferent nerves on,
176
Tone of, 175, 176
Ascidians, excretory organ in, 152
Ascites, causes of, 149, 161
Association, centres of functions of,
312
Athletes, training of, 208
Atropine, induction of glaucoma by,
141
Auricle—
Contraction of—
As showing by intra-ceso-
phageal hae 91, 92
Indicated by * wave, 95
Filing of—
Influenced by
ventricle, 105
Possible factor in production
of ‘‘v”’ wave, 103, 104
Left, movements of, 68, 69
Movements during cardiac cycle,

systole of

Of heart, 43
Degree of see valley, 49
Distribution of
cells in, 46
Stimulation of, result, 57
Precedence of beat in right or
left, 66
Pressure in—
““C ”’ wave, normal event of
curve of, 97, 99
Experiments on, 75
Fall of, cause of ““y”’ de-
pression, 107
Pressure waves, 83
Relaxation of, 105, 106
Right, chief function, 67
Stretching of — of, factor in
production of “x” and By tae
depressions, 107
Tetanisation of, 95
Auricle and ventricle in mammalian
-heart; muscular connection be-
tween, 39, 63. See also Auriculo-
ventricular bundle

ganglion ~

428

Auricles—
Contraction of both, graphic re-
cords of, 73
Function as reservoirs, 103, 106
note
Auricular—
Canal, 44
Of human heart, 38
Cycle, relationship to
cular, 82
Ring, 38, 39
Invaginated portion of, 39
Stimulation of, result, 57
Systole, 67, 69
Auriculo-Ventricular (A-V) Bundle—
Agent and means of passage of
conduction of impulse, evi-
dence for, 61
‘** Antidromic ”’ conduction in, 66
Description of, 39-43
Isolation of, 36
Microscopic appearances, 41
Nerve-fibres in, 47
Position of, 45
Auriculo-Ventricular—
Groove, 53, 67, 69
Line movements of, 103, 106
Node, 40, 59
Node and nodal rhythm, 60
Valves, position of opening, 81,
107
Axis-cylinder of nerve fibre, 278

ventri-

BACTERIAL Toxins, collapse due to, 179
Bat, visual acuity in, 374
Bidder’s ganglia, extirpation and
stimulation of, 54, 55
Bioplasm—
Chemical nature of, 6
Crystalloids kept in union with
cell by, 26
Birds—
Infundibular element in wing of,
186
Vision in, 374
Bleeding, explanation of success of,
173 1
Blindness—
Blue or blue-yellow, 401
Hemeralopia, 372
In relation to the cortex, 292
See also Colour Blindness
Blood—
Alkalinity of, during muscular
activity, 241
Carbohydrate material present
in, 14
Channel system, 131
In Turbellarian worm, 132,
134 ; undifferentiated and
unorganised, 132, 134

INDEX

Blood (continued)—
Circulation of. See Circulation
vee toxic influence of,
7

Deficient flow, cause of varicose
veins, 130

Dependence of function of nerve
cells on supply of, 115

Deprivation of amount trans-
fused, fatal effect of, 167

Determined to abdomen by
mental work, 148, 149

Determined to peripheral parts
by emotion and movements,
148, 149

Distribution of, throughout lung,
187

Flow of, how increased, 167, 168

Glands, 132

Influence of chemical state on
circulation, 171

Injection of, to excite callous
formation, 116

In peripheral fields, 177

Osmotic energy of, 169, 170

Quantity in brain, 149

Serum, depression of freezing-
point, 21, 28 ;

Serum, percentages of chlorides
and phosphates in, 24

Stagnation of, in shock and
collapse, 180 ;

Supply, arterial, temporary
arrest followed by active
hyperemia, 171

Supply of, to nephridial tissues,
152

Supply, plethora of, effects, 165

Transfusion from artery to vein
in cases of shock, 179

Transfusion of, in excess, effects
of, 165, 166

Viscosity of, 167, 168

Volume, ventricular, changes in,
not indicated by curves of
intra-ventricular pressure, 79

See also Corpuscles

Blood Pressure—

Arterial, 123, 127, 146, 176

Capillary, 149, 156

Causes of increase in, 234

Determined by various positions
of holding limbs, 142, 143.

Effect of mental work and
‘emotion on, 147

Effects of expiration, inspiration,
and respiration on, 144, 146_

Fall of, in shock and collapse, 180

Fall of, in spinal anesthesia, 180 —

Intra-pleural effects of, 146

_ Venous, 128

Blood-vessels—
Coats of, development, 132, 133
Collateral, compensatory enlarge-
ment following thrombosis, 164
= of, in muscular work,
236
Structure of, how developed, 133
See also Arteries, Capillaries, and
Veins
Body heat, loss of, in shock and
collapse, 180
Body, movements of, factor in main-
tenance of circulation, 144
Brain—
Arteries in, pulsatile expansion,
139
Cortex—
Cell laminz of, 287
Development of, 289
Evolution of cerebral func-
tion, 316
Excitation of, raises arterial
pressure, 147
Higher functions of, 318
Histological method of local-
isation, 300, 305
Lamination of, 285, 291, 294
Localisation of function,
284-350
Marie’s doctrines, 338
Prefrontal region, 292, 310,
312, 314
Regions of, 292, 307
Quantity of blood contained in,
varies little, 149
‘** Brain pressure,” definition of, 137
** Brain-workers,”’ irritable dyspepsia
of, 149
Breathing. See Respiration
Brightness values, 370
Broca’s aphasia, 331
Bronchiole, terminal, 185
Bronchioles, musculature of, 186
Bulbus cordis, 45

Burch apparatus for study of achro-
matic t holds, 357

CatcrvuM salts, effect on heart muscle,
‘3

Callus—

Rapid formation of—
By injection of blood, 116
_ Under action of warmth, 172

Blood pressure in, 135, 156, 157
Hypothesis of filtration by,

149, 150
Method of estimation, 135,
141, 142
ve tissue cells act as
walls of, 131

INDEX 429

Capillaries (continued )—
Distended, passage of water
from, 170
Excess of blood lodged in, 165
Surface tension of, 169 note, 170
Capillary system, nature of, 134
Capillary-venous pressure, 150, 156
In brain and eyeball, 138
In kidney, 153, 154
Carbohydrates, value of, 251
Carbon-dioxide—
Amounts of, effects of, 31
Percentage of, in alveolar air, 238
Carboxyl group in amido-acid, 7
Cardiac cycle, human, pulse records
in relation to events of, 72-111
Cardiograms, time relations of ventri-
cular movements dependent on, 77
Cardiographic curves, uncertainty of,
87

Cardio-motor centre, 59
Carotid artery—
Contractility greater than that
of aorta and pulmonary artery,
118
Union of peripheral end of
external jugular vein to
central end of, 112, 113
Carotid, primary wave of synchronous
with ‘‘c”’ wave of venous pulse,
Carotid pulse, value as standard
movement, 80
Cat, transplantation of kidneys of,
114, 115
Cells—
And fats, union between, 15
Chemical, concentration and
fluid, effect on nervous im-
pulse, 276, 280
Effect of osmotic pressure on, 4
Electrolytes in, 25, 274
Energy supplies of, |
Equilibrium between ion and
cell, 20
Influence of drugs on, 32
Lamine of the cortex cerebri,
287; functions of, 294
Living, colloid and crystalloid
in, equilibrium of, 1-33
Living, union between, 14
Neurilemma, multiplication of,
272 ‘
Osmotic pressure and, 25, 28
Potassium and ions in, 17, 275
Sodium and chlorides in, 17, 23,
275
Solubility of cell substance, 19
Centres—
Association, myelination of, 300 ;
functions of, 312

430

Centres (continued )—
For language, 285
Sensory, myelination of, 300
Word, 324
Cerebro-spinal fluid, pressure of, 137
Chemical cells, 276, 280
Chemical stimuli for producing con-
tractility of cardiac muscle, 48
Chest, increased pressure in, factor
in production of venous pulse, 106,
107
Chick embryo, creatin in, 215
Chloral—
Conversion of pressor into de-
pressor reflexes by, 176
Injurious action on heart, 179
Intra-venous injection of, effects,
179
Chlorides in corpuscles and serum, 24
Chlorides in nerve fibres and cells,
275, 278
Chloroform—
Conversion of pressor into de-
pressor reflexes by, 176
Effect of, on the heart, 4
Chloroform anesthesia and electrical!
conductivity, 280
Cholera, viscosity of blood in, 168
Circulation of blood—
Dependent on bodily movement,

143

Effects of muscular exercise on,
228

Effect of respiratory muscles on,
153

Means for determining volume
of, 148

Obstruction of, at two points
during half of cardiac cycle,
106 note
Pulmonary obstruction of, effect
on output from heart, 146
Sluggish, in sedentary workers,
149
Therapeutic effects of accelera-
tion, 149
Varies with changes of posture
and muscular contraction, 144
Circulation and respiration, abnormal,
due to adhesions following medias-
tinitis, 190
Circulatory system, comparative ana-
tomy and histology of, 131
Clothing, effect of unsuitable, 247
Coagulation, protein, influence of
temperature on, 212
Ceelomic fluid, 152
Collapse, 173-180
: aused by injection of bacterial
toxins, 179, 180
Reflexes ceasing during, 180

INDEX “Sa

sass equilibrium of, in living onthe
3

Colloid union with crystalloid, 12
Colour—
Genesis of, 381
Mixing of, 387
Sensations—
Mixing of, 354
Purkinje’s phenomenon, 353
Young—Helmholtz theory,

403
Three-colour hypothesis _—_ of
Young, 403
Toned, brightness and darkness
of, 417

Colour-blindness—
Partial, 392, 395
Total, 360, 375
Hering’s case of, 361
Luminosity values of, 363
Colour-vision—
Normal, 396
Theories of, 378-425
Ceaser blindness and deafness,
328

Congestion, production of, 162
Connective tissue cells act as walls
of capillaries, 131
Contraction, muscular, determination
of, 48, 51, 98, 226
Corpuscles, chlorides. and phosphates
in, 24
Cortex cerebri. See Brain, Cortex
Costal cartilages—
Loss of elasticity, 195
Respiratory movements of, 198
Creatin in muscle, 169, 215
Cribriform ligament, sclerosis of, 141
Crystalloid—
Chemical reaction of, 12
ar of, in living cells,
Cycling, heart beat and blood pressure
during, 235

DARKNESS, effect on vision, 353
Deafness, causes of, 328
Death, vascular residual pressure in
animals after, 157
Depressor reflexes, 176
Deuteranopes, 396; stimulus values
for, 400
Dextrin in muscle, 213
Dextrose, effect of, on heart muscle, 2
Dextrose, injection into blood causing
hydremia, 169
Diaphragm—
Action of, 199
Piston-like, 200
Variability, 200
Antagonist of, 192 ~

l
_ Descent of, 147 See also Respira-
tion, abdominal
Movements of, 199
Muscular crura of, 190
oe of, 193 been,
aralysis of, collapse confined to
lower pulmonary lobe, 191
i tic pulmonary surface
directly expanded, 187
Diaschisis, 331
Dichromatic systems of vision, 423
Diet in relation to muscular work,
249
Diphtheria toxin, injection of, col-
apse following, 180
i , action of drugs upon, 32

: Dog—

Amputation and replantation of
thigh in, 113
Stomach of, subject to hyper-
mic reaction, 171
Dropsy—
Cause of, 149, 161
Cardiac, causation of, mechanical
theory, 162
Drugs—
Aetions of, 5, 32
Antagonistic action of, 20
Effects of on cells, 32
Dudgeon’s sphygmograph, 86
Duplicity theory of vision, 371
Dyspepsia, irritable, of brain-workers,
149

Dyspnea, causes of, 238, 241

Ear, middle, new instrument for
graphic records of, 77

Einthoven’s electrocardiogram, 93
note

Einthoven’s string galvanometer, 76,
77, 109

Elasticity, muscular, 210

Electric currents of nerves, 274-280

Electrical conductivity and chloro-
form anesthesia, 280

Electrical —— in excised

city, animal, a “ diosmotic

Electrocardiogram—
Einthoven’s, 93 note
J curve shown simul-
taneously with electrocardio-
gram, 108, 109 a je
experimental application
to heart, 70

of granules by, 279
In cell and nutrient medium, 25

INDEX 431

Electrometer, capillary, for graphic
records of heart sounds, 76
Embolism, arterial, how compen-
sated, 164
Embolus, downward movement in
large veins, 164, 165
Emotion—
Determines blood to abdomen,
148, 149
Effect on blood pressure, 147
Evolution of, 319
Emphysema—
Cause of, 195
Hyperdistention of infundibula
in, 186
Energy supplies of the cell, 1
Energy value of foods, 251
Equilibrium between cell and ion, 20
Equilibrium of colloid and crystalloid
in living cells, 1-33
Equilibrium, osmotic of the cell, 28
Ergograph of Mosso, 226
Ether anesthesia and electrical con-
ductivity, 280
Evolution of cerebral function, 316
Excitatory wave of heart impulse, 65,

Excretory organ—
In Ascidians, 152
In unicellular animals, 151
Exercise, muscular—
Cardiac and circulatoryeffects, 228
Effects of, 224
Over-exhaustion from, 127, 128
Physiology of, 208-257
Therapeutic effects of accelerated
circulation under, 149
Types of, 223
Expiration—
Effect on blood-pressure, 145
Normal, action of respiratory
muscles in, 192
Prolonged, effect on
pressure, 129
Extra-systole—
Method of production, 52
Ventricular, 74
Eye—
Adaptation of, to light, 351
(@dema of tissues of, in glau-
coma, 141
Retina of, rods and cones of, 373
Retina, sensitiveness of, to light,
358
Sensitivity to light, 420
are of, response to, 352,

Eyeball—
oe in, pulsatile expansion,

139
Capillary-venous pressure in, 138

'

venous

432

FarnTINnG, cause of, 173
Fat and cells, union between, 16
Fat—
Energy, value of, 251
Present in muscle, 213
Fatigue—
Muscular—
Causes of, 254
Lactic acid, produced by,
214
In nerves, apparent absence of,
266; influence of anesthetics
on, 268
Femur, amputation and replantation
of, in dog, 113
Ferments of muscle, 217
Fibre lamine of the cortex cerebri,
288
Fibres. See Nerves
Filtration hypothesis of capillary
pressure, 149, 152, 156, 170
Flechsig’s area for bodily sensibility.
306
“Flicker ’’ method in colour sensation,
354
Fluid cells, theories based on, 280
Foetus—
Cerebral cortex of, 296
Movements of, 219
Food—
Comparative energy values of,
251
Conservation of energy and, 221
Influence of, on output of
nitrogen, 248
Ingestion of, raises arterial pres-
sure, 127
Fovea centralis, sensitiveness of, to
light, 358
Freezing, permanent relaxation cf
arteries by, 117
Freezing point, depression of, of blood
serum, 21, 28
Frog, heart of, experiments on, 50, 70
Infundibular element in lung of,
186

GALVANOMETER. See String galvano-
meter, Einthoven’s, 76, 77
Ganglion, sensori-motor, 317
' Ganglion cells—
Heart-beat, independent of in-
vasion of, 58
In vertebrate heart, 45, 47
Gases, respiratory, pressure of, 30
Glands, formation of, progressive
evolution of, 153
Glandular system, influence of mus-
cular work on, 252
; rere causes and treatment of,

INDEX eS

Glycogen in the cell, 15
In muscle, 212
a egies following hyperglycemia,

Pee cell lamina of cortex cere-
bri, 296
Graphic records—
Of heart sounds, 76
Tnstrument for, 77
Marey’s receiver for, 75
Simultaneous from different pul-
sating points, value of, 72

H2MODYNAMOMETER, radial, maxi-
mum pulsation method, 124, 126
Hemoglobin—
Attachment of ions to, 23
Formed with oxygen,a dissociable
compound, 11
Hemorrhage, into connective tissues
to be avoided in operation on
kidneys. 116
Harrison’s sulcus, 188
Heart—
Action of—
Effect of transfusion of
blood on, 166
Increase by strychnine, 178
Vagus nerve on, 54
Adhesion to roots of lung, 190
Automaticity of, 47, 49, 59, 64
Block, 104, 106
Definition of, 73
Partial, 95
Cardiac cycle, 72-111
Effect of chloroform on, 4
ee of muscular exercise on,
28
Excitability of, varies in different
parts, 4
Experimental action of drugs on
different parts of, 58
Function of, 144
Human—
Auricles of, 38, 43, 68, 91
Sinus venosus in, how re-
presented, 37
Ventricles of, 44
Injurious action of chloral on,
179
Mammalian, muscular connec-
tion between auricle and
ventricle in, 39. See also
Auriculo-Ventricular Bundle
Microscopical anatomy of, 34
Movements of, 65, 76
Output of blood from, 146

Power of, how develo 133

Some. Frere Raya of, 76°
pec orm 0

region of blood channel, a

Hes leontinued)—
Vertebrate—

’ Morphology of, 36
Nervous elements of, 45
Primitive, chambers of, 36
Wall, direction of movement of
different parts of, 103
See a'so Auricle and Ventricle
Heart beat—
And inorganic ions, 3
Effect of oxygen pressure on, 4
Experimental methods for pro-
ucing cessation of, 48
Independent of invasion of
anglion cells, 58
Influence of muscular work on, 236
Revival after death, 58
See also Pulse

- Heart impulse—

Conduction of, 64

Excitatory wave of, 53, 56, 65, 70

Muscular conduction, 60

Site of origin, 59

Heart muscle—

Contraction of, 48, 51, 98

Effect of dextrose on, 2

Effect of sodium chloride on, 2

Excitability of, 48

Fibres of, 34

Nature of, 34, 36

Of invertebrates, how differing
from that of vertebrates, 56

Properties of, method of study
during beat, 51

Relaxation of, 52, 53

Rhythmic stimulation, effect, 5

Tetanisation, 51, 56 7
Tonicity of, 52, 53
Heat—
Body, loss of in shock and
collapse, 180

Effect of muscular work on, 244
Production of hyperemia by, 172
ing to 50° C., permanent relaxa-
tion of arteries produced by, 118
Hemeralopia, 372
Hens. See Leghorn hens
ity and muscular activity, 218
ngs theory of visual sensations,

. acid, 8 :
hle’s differential manometer, 76
"s manometer, 86

Hydremia, 168-170

a of on tissues and viscera,
Production of, 158, 162

41

Hydrostatic pressure—
Compensation for, 143
- Mean, 157, 159
Variations of, 142

INDEX

433

Hydrothorax caused by experimental
obstruction of vene cave, 160
Hyperemia, 170-173
Active, origin and production of,
170, 172
Passive, 164
Due to venous congestion,
170
Resorption favoured by, 172
Procreative and _ reproductive
functions accompanied by, 172
Reaction to, in stomach of dog,
rabbit, and man compared, 171
Hyperpneea, causes of, 238, 240

IMAGE, striping of, 373
Images, after-, 402, 408
Infants, grasping power in, 219
Inflammation, processes of, relieved
by flow of lymph, 139
Infundibula—
Function and nature of, 185
Hyperdistension in emphysema,
186
Injuries, severe, production of shock
by, 173
Ink polygraph, Mackenzie’s, 86, 93
Inosite in muscle, 213
Insecta, nephridial tissues in, 152
Insectivora, functions of brain in, 3l4

Inspiration—
Effect on blood pressure, 145, 146
Prolonged, effect on venous

pressure, 129
Instinctive activities, localisation of,
297
Intellectual processes,
upon language, 322
Intercellular fluid, 152
Intestines, hyperemia, after produc-
tion of temporary anemia, 171
Intra-cranial pressure increased by
inflammatory processes, 137, 139
Intra-ocular pressure increased by
inflammatory processes, 139
Tons—
Cells rich in, 17
Inorganic, and heart beat, 3
Phosphatic, cells rich in, 17
Presence of, in cells, 1
Various, distribution of, in cell
and fluid, 19, 23 d
Iridectomy, relief of glaucoma by, 141
Isoelectric nerves, 259
Isotonic and isometric curves of con-
tractility of cardiac muscle, 49

Jornts, drugs introduced into, subse-

~quentl pearing in urine, 172
Lalas Bulb, curves and traces from,
85

2E

dependent

434

Jugular pulse—
** A” wave, delay in onset, 93
*“C” wave, component part of,
99
*C” wave synchronous with

primary wave of arterial pulse,
102
Curve shown simultaneously

with electrocardiogram, 108

See also Venous pulse

Jugular vein—

External peripheral end united
to central end of carotid
artery, 112, 113

Pulsation in and tracings from,
85

KIpNEY—

Capillary-venous
153, 154

Disease, cedema in, explanation
of, 169

Excised, perfusion experiments
on, 154

Functions of, 156 :

Influence of protein on, 249

(Edema, production of, 163

Rhythmical squeezing by respi-
ratory muscles, 153 é

Transplantation of, experimental,
114, 116

Tubules of, 153, 155, 156

See also Excretory Organ;
Nephridial tissues

pressure in,

Lasour, bodily, effect on viscosity
of blood, 168 :
Lactic acid, 213, 254
Lactose, introduction into joint and
appearance in urine; 172
Language, 319
As instrument of thought, 322
Centres, localisation of, 285
Leghorn hens, black and white, ex-
change of ovaries in, 116
Leg, cedema, production of, 163
Legs, hereditary oedema of, 130
Levatores costarum, 205
Light—
As stimulus to the eye, 352
Coloured, achromatic threshold
of, 355
Mixing of, 387
The medium of vision, 382
Limbs—
Determination of blood pressure
by various positions of hold-
ing, 142, 14
(Edema in, 130, 163, 169
Lipoids, cells surrounded by, 18

INDEX

Liver—
Engorgement of, effect on heart,
233

Pulse, auricular, 100
Loven reflexes, 176

Lungs—

a ry of, inspiratory position,
85

Area of increased resonance
round localised consolidation
in, 188

Collapse of, 191, 194 >

Division into, functional signi- —
ficance of, 190

Elasticity of, 184, 192, 193
Extensibility of, 184, 188
Inflation of, after death, 185
Infundibula essential, expansile
parts of, 186
Lobes of, 190
Male and female differences be- _
tween, 191 ‘
Prolonged ventilation of, effects
of; 31
Reflex contraction of, 186
Roots of, 189, 190
Sedentary habits produce disuse
of parts of, 188
Ventilation of, during exercise,
238
Zones of, 184, 186
See also Circulation of blood,
pulmonary
Lymph—
Flow of—
From salivary gland, 150
Production, 169, 170
Formation of, 156, 157
Mechanical theory of, 149

MACKENZIE’S ink polygraph, 86, 93
Mackenzie’s receiver, 86
Mamma», arteries of, tortuosity, 120
M os
Functions of brain in, 295, 314
Infundibular element in lung of,
186
Manometer, 105, 121, 135, 137, 141,
146
Alteration in tension of ventricle
wall measured by, 49
Hiirthle’s, 86
Differential, 76
Manubrio-sternal joint— ;
Anchylosis, late occurrence in
life, 196
Limitation in movement as.
cause of phthisis, 197 3
Respiratory significance, 196
Marasmus, extensibility of arteries.
in, 120 ;

nay, 7 variations in the pulse

after, 230, 233

Marey’s receiver for graphic records,
5

7
Marie’s doctrines on cerebral localisa-
tion, 338

‘Mediastinal pulmonary surface, in-

directly expanded, 187
Mediastinitis, adhesions due to, caus-
ing abnormal respiratory and cir-
culatory movements, 190
Medullary centres, effect of spinal
anesthesia on, 180
Mental disease—
In relation to the cortex, 293
Proportion of cases to general
population, 313
Mental disease and “alteration of
personality,’’ 343

Mental work—

Determines blood to abdomen,
148, 149
Effect of, on blood pressure, 147
Mesocardia, functions of, 65
Metazoa, nephridial functions in, 152
Microphone for graphic records of
heart sounds, 76
Mole, sensory association in the, 314
Molecules, protein structure of, 7
Molluses, circulatory system in, 131
Mosso’s experiment, 148
Motor aphasia, 331
Movements—
Active, send blood from abdomen
to peripheral parts, 148, 149
Analysis of, by Marey and Muy-
bridge, 220 r
Factor in maintenance of circu-
lation, 144
See also Exercise

_ Muscearine, effect of on heart beat, 48
uscle—

Abdominal, effect of stimulation
of phrenic nerve on, 192

Cardiac, properties of, 47-53

See also Heart muscle

Chemical properties of, 210

Contractility, means of, 49

_ Contraction, voluntary, 225

Intercostal action of, 204 ,

Nitrogenous extractives of, 214

Of ventricle, function of longi-
tudinal layer, 67, 68

Protein constituents of,. 211

Physical properties of, 210

ry, action in normal

INDEX

435

Muscle (continued )—
Structure of, 209
See also Respiratory muscles
Muscular—
Conduction of heart impulse, 60
Exercise, See Exercise
Fatigue. See Fatigue
Work, physiology of, 208-257
Musculi pectinale of auricle, 67
Mustard poultices, hyperemic action
of, 173
Myogenic theory of excitatory wave,
54, 56, 58, 63
Myosinogen of Halliburton, 211

Necrosis, due to closure of terminal
arteries, 164
Neopallium, 315, 317
Nephridial tissues, 151, 152
Supply of blood to, 152
Nerve cells—
Action of —
Chloroform on, 5
Strychnine on, 14
Function dependent on supply
of blood, 115
Nerve-fibres—
Axis-cylinder of, 278
Central origin of, 270
Chlorides and potassium in, 275
In auriculo-ventricular bundle,
47
In vertebrate heart, 45, 46, 47
No growth of, from peripheral
ends, 269, 271
Regeneration of, 268
Nerves—
Activity of, theories of, 274
Afferent, pressor and depressor,
action on muscle of arterioles,
176 .
Chemical concentration and fluid
cells of, 276, 280
Degeneration, chemical pheno-
mena of, 16
Electric currents in, 274
Electrical conductivity of, 280
Endings in vertebrate heart, 46
Excised medullated eimai
connected with, 26
Fatigue in, apparent absence, 266
Impulse, effect of chemical and
other cells on, 276, 280; expen-
diture of energy and, 267
In living animal, 262
Isoelectric, after excision, 259
Physiology of, 258-283
Nervous system, influence of on the
heart, 231
Neurogenic theory of excitatory
wave, 54, 55

‘

436

Neurone theory, 269

Neutral point of spectrum, 397

Night-blindness, 372

Nitrogen, excretion of, determination
of, 248, 251

Nitrogenous extractives of muscle,
214

Nodal rhythm, 60

(pEMA—
Causes of, 149, 160
In limbs due to hydizemia, 169
In renal disease, explanation of,
169
Occurring under normal venous
and arterial pressure, 161
Of legs, hereditary, 130
Production of, 163
(sophagus, tracings from within, 91,
93, 97
Oil, injection of, into pericardium,
158
Organs, transplantation of, from one
animal to another, 112, 113
Orthodiascope, 205
Osmosis, 154, 156
In capillary system, 134
See also Blood, osmotic energy
of
Osmotic—
Energy, 169
Equilibrium of the cell, 28
Pressure, 4, 6, 161
Pressure and cells, 25, 29
Ovaries, exchange of, in black and
white Leghorn hens, 116
Oxygen—
Hemoglobin formed with, 11 fi
Inhalation of, raises arterial
pressure, 128
Pressure of, effects of, 30
Pressure, effect on heart beat, 4

Pancreas of rabbit, 153
Paralysis—
Motor, in spinal
limitations, 180
Of constrictor synapses, 177
Of diaphragm, 191
Of vaso-motor centra, 174
Of vaso-motor nerves,\ 179
Parameecium, vacuoles of, 151, 152
Para-myosinogen of Halliburton, 211
Perception and sensation, 319
Pericardium, injection of oil into,
158
Peripheral ends of nerves, regenera-
tion from, 271
Personality, alteration of, 342
Phagocytosis, increase by warm and
stimulating agencies, 173

anesthesia,

Phi

Cy ae
Pie Te

INDEX

Phosphates in corpuscles and serum,
24 ¥

Phosphorus poisoning, extensibility
of arteries in, 120
Phrenic nerve, stimulation of, effect
on abdominal musculature, 192
Phthisis, production through limita-
tion of manubrio-sternal joint, 197
Physical deterioration, causes of,
208, 222
Physiological saline solution, injec-
tions of, 158, 161, 168
Pial veins, pressure in, 137
Pigment of muscule, 217
Pituitary extract, constricting effect
on arteries restores blood pressure,
177
Plasma—
‘* Antitropic ”’ action of, 172
Flow of, 173
Plethysmograph—
Records by, 166
Volume of blood-circulation in
arm recorded by, 148
Pleurisy, lower pulmonary lobe most
affected in, 191
Pocket sphygmometer with
enclosed bag, value of, 126
Poiseuille formula, 136
Polarimeter, 172
Polycythemia, viscosity of blood in,
in, 168
Polygraph, 86, 93 4
Popliteal nerves, regeneration after
suture, 273
Portal vein, constriction of, 161
Post-sphygmic interval, 79
Posture—
Effect on blood pressure, 129,
143
Effect on circulation, 144
Potassium—
Cells rich in, 17, 275
Distribution of in axis-cylinder,
278
Ferro-cyanide solution introduc-
tion into joint and appear-
ance in urine,
In muscle, 217
Salts, effect on heart muscle, 3
Poultices, hot, induction of hyper-
zmia by, 173
Presphygmic interval, 79, 100
cure working estimate of, 80
Pressor reflexes, conversion into de-
pressor, 176
ure—
Aortic, and in vena cava, 157,
159
Atmospheric, effects of, 30
Auricular, 75, 83, 97, 107

large

Pressure (continued) —
Capi venous, 150, 156
tic, 142, 157, 159
Osmotic, 4, 6, 161
Cells and, 25, 29
Effects of chemical union, 10

Respiratory gases, 30

See also Arteries, Blood pressure,

and Ventricle
Prison diet, 249
Procreative functions accompanied
by hyperemia, 172
Protanopes—
Stimulus valves for, 400
Proteins—
Action of, upon blood serum, 22
Bodies, 6
And carbohydrate, union of, 15
In food, value of, 249
Of muscular plasma, 211
Protoplasm, chemical nature of, 5
Pseudo-arthrosis, excitation of callous
~ pee in, by injection of blood,
116
Pulmonary artery, contractility less
than that of carotid, 118
Pulse—
Human, advantages of study, 72
Irregularities, significance not
always pathological, 74
Rate, effect of exercise upon, 228
Study of from physiological ex-
periments on animals, 73
Variations in, in rest and exer-
cise, 230
* Youthful irregularity ”’ of, 74
See also Jugular and Venots
pulse
Pulsus oxus, normal as well as
pathological event, 146
Pupil, contraction of, 368
Pupillo-motor response, apparatus
or, 369
Purkinjé—
Cells, 41
Fibres, nature of, 39, 64, 98
Phenomenon, 352
dal—
- Layer of the cortex, 287, 296
Seat of psychic function, 295 |

RasBsBirs—
Creatin in muscles of, 215
Pancreas of, 153 :
Stomach of, not subject to
_ hyperemia reaction, 171

Radial artery, eerertion of sphyg-

mometer to, 1
Radial

INDEX | 437

Rectal sound, volume of blood circu-
lation in abdominal organs re-
corded by, 148

um—
Blood pressure in, use of, 146, 147
Temperature in the, 244

Reflexes—

Conversion of inhibitory, 177
See also Pressor, and Depressor
reflexes

Regeneration of nerve fibres, 268

Relaxation, muscular, accompanying
pleasurable feelings, 149

Remak’s ganglia, 54

Renal vein, flow from compared with
ureteral flow, 154

Reptiles, infundibular element in
lung of, 186

‘** Residual affinities ’
10, 13

Residual vascular pressures in the
dead animal, 157

Respiration—

Abdominal—
Effect on blood pressure,
144, 147
Movements of roots of lung
under, 190
Artificial, determination of best
method for, 194
Diaphragmatic movements of
roots of lung under, 190
Effect of excess oxygen on, 31
Human, mechanism of, 182-207
Influence of muscular work on,
237
Pumping action of, 144-147
Rate of, effect of muscular work
on, 243 ;
Thoracic—
Effect on blood pressure, 144
In supine position, how
produced, 192, 193
Movements of roots of lung
under, 190

Respiration and circulation, abnor-
mal, due to adhesions following
mediastinitis (Wenckebach), 190

Respiratory movements in the foetus,
219

Respiratory muscles—

Effect on circulation, 153

’

or adsorption,

Rhythmical squeezing of kidney.

by, 153
Retina, See Eye
Rhythm, low, of conservation to
hysiological stimuli, 52
Rib, Bret, respiratory significance, 196
Ribs—
wieeding: respiratory movements,

438

Ribs (continuzd)—
Respiratory movements of, 20]
Upper—
Mechanism different from
that of lower, 205
Respiratory movements, 204
Spinal articulations, 204
See also Costal cartilages
Ringer’s solution, 115
Action of, on nerves of heart, 58
Effect on heart beat, 4
Experimental injection of, 168
Rods and cones of retina, 373
Rubber bag for armlet, 121
Rubber pneumatic suit for use in
shock, 178
Running—
Composition of alveolar air in,
242
Variations in the pulse after, 231

SALINE, physiological, placing heart
in to produce cessation of beat, 48
Salivary cells, 151
Salivary gland, flow of lymph from,
150, 151
Salts—
Inorganic—
Of muscle, 216
Present in cells, 17
Sarcolemma and sarcoplasm, and
sarcostyles of cardiac muscle fibres,
35
Schlemm’s canal—
Venous sinus of, 138
Walling in of, 141
** Second wind ”’ and the composition
of alveolar air, 242.
Sedentary work, sluggish circulation
due to, 149
Semilunar valve, closure of, 104, 107
Sensation—
Head’s experiments in, 271
Localisation and, 319
Senses, special, physiology of, studies
in, 351-425
Sensibility, bodily, Flechsig’s area
for, 306 .
Sensory aphasia, of Wernicke, 33
Sensory centres, 300
Sensory “‘ receptors,’ 144
Septum—
Inter-auricular, 40
Inter-ventricular, origin and
mode of development, 44, 45
Shock, 173-180
Causes, 173, 174
Methods of production, 174
Reflexes ceasing during, 180
Rubber pneumatic suit for con-
fining body in, 178

INDEX eae

Shock (continued)—
Simple, transfusign of human
_— from artery to vein in,
Sibson’s fascia, 187
Sight. See Vision
Sino-auricular groove, 54
Sino-auricular node, 40, 59
Sinus venosus, 44
In human heart, 37
Skeletal muscles, function of, 144
Sleep. influence of, on muscular
system, 224
Sodium chloride, effect of, on heart
muscle, 2
Spectrum—
Intensities of lights in, 387
Neutral point of, 397
“Twilight ”’ values of, 362
And visual sensation, 355
Sphygmogram, clinical information
afforded by limited in value, 72
Sphygmographs, 75
Application by suspension me-
thod, 144
Dudgeon’s, 86
Sphygmography, methods of, 75
Sphygmomanometer, 144
Sphygmometer—
Bags, small, unenclosed, errors
introduced by, 125
oe eee to radial artery,

(Hill’s) description of, 122
See also Pocket Sphygmometer
Spinal anesthesia. See Anesthesia,
spinal
Spinal cord, division of, shock re-
sulting from, 173, 174
Spine—
Double articulation of upper
ribs to, 205
Extension of, as means of ex-
panding thorax, 205
Standard movement, value of, 77, 80
Stannius ligature experiment, 48, 54,
59
Sterno-costal pulmonary surface di-
rectly expanded, 187
— inspiratory movements of,
Stimulus— >
Normal visual, 387
Values for Deuteranope and
Protanope, 400
Stochiometric relationships, 12
Stomach—
Of dog subject to hyperemic
reaction, 171
Of rabbit and man, not subject

|

to hyperemic reaction, 171 |

ae "I

- Stovain,
by stovain, 180
as galvanometer, Einthoven’s,
1

hnine— .
Action of, on nerve cells, 14
Favourable action of, 177

ugar—
In the blood, 14
jection into blood causing
ydremia, 169, 170
In muscle, 213
Sweat, secretion of, and muscular
work, 246, 252
Sweating, effect on viscosity of blood,
168
Sympathetic nerve, how long active
after death, 58
| Syncitium—
Definition of, 34, 36
Heart muscle regarded as, 36

8 7 a
ey onstrictor, paralysis of, 177, 178
Sensory, 175, 177
In spinal anesthesia, 180
Of vaso-motor centre, 179
Syncope, restoration from, 173
Systole, onset of, in man, not easy to
fix, 76

TnI terminalis, 66, 67
Temperature—
uence of muscular work on,
243
Influence on nervous impulse, 276
Influence of, on protein coagula-
tion, 212
Tetanisation—
Of auricle, 95
Of heat muscle, 51, 56 -
Thigh. See Femur
Thorax—
Compression of, results, 195
Elasticity of, respiratory valve,
193, 194
Expansion of, 194
By means of extension of
spine, 205
' Horizontal groove on each side
of, 188
aa or operculum of, 196, 197
Wal of pressure in, 188
of, adhesion of roots of
ung to, 190
Thrombors compensato enlarge-
ment of collateral iekiwibedis

passage of water from

capillaries into, 170

INDEX
spinal anesthesia produced —

439

Torcular Herophili, 137
Toxins. See Bacterial toxin; Diph-
theria toxin
Trachea, blood pressure in, rise of, 146
Training. See Exercise
Transfusion of blood, in excess, effects
of, 165, 166
Tricuspid regurgitation, ‘‘ v ”
and, 102 and note
Tuberculosis—
Pulmonary—
Initial site of, 198
And mechanism of respira-
tion, 206
Turbellarian worm,
system in, 132, 134
Turkish baths, effect on viscosity of
blood, 168
Turpentine stoups, hyperemic action
of, 173

wave

blood-channel

UNICELLULAR
organ in, 151

Unions, chemical and physical, 12

Ureter, flow from, compared with
flow from renal vein, 154

Urine, resorption into, of drugs intro-
duced into joints, 172

Uterus, arteries of, tortuosity, 120

animals, excretory

VACUOLES of Paramececium, 151, 152
Vagus nerve—
Action on heart, 48, 54
How long active after death, 59
Valsalva’s experiment, 146
Varicose veins, due to deficient flow
or quality of blood, 130
Vascular pressure, residual,
dead animal, 157
Vascular system, experimental opera-
tions on, 112
Vaso-constrictor impulses, 176
Vaso-dilatation of active organs, 176
Vaso-dilator impulses, 176
Vaso-motor centre—
Paralysis of, 174
Synapses of, 179
Vaso-motor nerves—
Excitation of, effect on blood
flow, 167
Paralysis of, 179
Veins— &
Abdominal and thoracic, citcu-
latory function, 66, 67
Blood pressure in, 128, 130
o/-am structure of arteries,

Large, downward movement of
embolus in, 164, 165

Over-engorgement, prevention,
106 note

in the

440

Veins (continued)—

Preservation of normal situation
and direction in operations on
kidneys, 115, 116

Small, excess of blood lodged in,
165

Transfusion of blood from ar-
teries to, in cases Of shock, 179

Transplanted portions of, in-
sertion between divided ar-
teries, 112

Union of—

Divided ends of, 112
With arteries, 112
See also Varicose Veins
Vena cava—

Inferior, obstruction, complete,
effect on venous pressure, 161

Residual pressure in, 157

Obstruction of, effects, 159, 160

Venous blood, effect of deep abdomi-
nal respiration on, 147

Venous congestion, value of, 172

Venous pulse, 84

a-c interval, 89, 93, 104, 109

‘“ A ” wave, factors producing, 95

“A”? wave, indication of auri-
cular contraction, 95-97

“A”? wave, factors producing,
97, 99

‘“C”? wave synchronous with
primary wave of carotid, 89

Depressions ey x: 99 #66 5. ead oe y 25
87-91 |

Elevations (Sa; “é Ce “ce ve
waves), 87-91

“Vv” wave, 89, 90, 102

“XxX” and ‘“‘x’” depressions,

factors producing, 105

‘““y ”’ depression, factors pro-
ducing, 90, °94, 107

Ventricle—

Beating, action of drugs on, 53

Contractility of, 50

Contraction of both, graphic re-
cords of, 73

Degree of excitability, 49

Distribution of ganglion-cells in,

4
Effect of high intra-cardiac pres- |

sure on action of, 70
Of heart in man, 44
Movements during cakdiac cycle,
68
Movements of, time relations, 77
Muscle of, 67
Pressure in—
Curves of, 79
Experiments on, 75

Printed by BALLANTYNE, HANSON & Co,
Edinburgh & London .

INDEX

Ventricle (continued)—
Stimulation of, result, 57
Systole of, 103, 105, 107
Wall of, alteration in tension, 49

Ventricle and auricle—

Muscular connection between,
39, 63
See also
Bundle

Ventricular cycle—

Relationship to auricular, 82
And standard movements, 77

Ventricular extra-systole, 74

Ventricular systole, 69

Ventro-lateral pulmonary

See Sterno-costal
Vestibule, terminal air space, 185
Viscera, abdominal upward draught

of, 201

Visceroptosis, 200

Vision—

Colour, theories of, 351
Dichromatic systems of, 423
Effect of colour on, 353

In birds, 374

Progressive evolution of, 299
‘* Recurrent,” 365

Twilight, agency of, 371

Sce also Colour vision

Visual mechanisms, theory of, 371, 375

Visual sensations, Hering’s Sheory of,

412
Visual stimuli, normal, 387
Visuo-psychie region of the cortex

cerebri, 292
Visuo-sensory area of the cortex

cerebri, 291, 296, 299, 306

Auriculo-Ventricular

surface.

WarmtTH, rapid formation of callus
under action of, 172

Water, adsorption and chemical
combination of, 10, 13

Weight lifting, effect on blood pres-
sure, 235

Word-centres, 324

Words, language and thought, 323

Work, muscular, physiology of, 208-
257

YOHINBIM—
Administration of— ;
Effect on blood flow, nig as
Effect on nerve fati

Young-Helmholtz theory o nate ra
sensations, 412

Z1G-ZAG experiment of Engelmann, :
60, 63 GaN

Zincativity of injured nerve, 260 ~ ;,

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