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A
MANUAL OF PHYSIOLOGY
Witb practical
BY
°N'.' STEW ART, M A ^ D Sc ^ M D EDIN ^ D
517
7. Urea ------ - 518
8. Ammonia in urine - - - - - '521
9. Total nitrogen in urine - - - 521
10. Uric acid ... . 523
11. Creatinin .... . 523
12. Hippuric acid - - - - - 524
13. Proteins in urine ... . 524
14. Sugar in urine - - 525
15. Pentoses in urine - - 528
16. Acetone in urine - - 529
17. Determination of the freezing-point of urine - - 529
1 8. Examination of urine - - 531
19. Urinary sediments - - 531
CHAPTERS X., XI., AND XII.
1. Glycogen . . 7j5
2. Catheterism - - - -
3. Experimental glycosuria . -
(1) Injection of sugar into the blood » - -
(2) Phlorhizin glycoauria .
(3) Alimentary glycosuria - - -
(4) Estimation of the sugar in blood - - -
4. Milk -
5. Cheese - - 719
6. Flour - - *. 719
7. Bread - ••• ... 720
8. Excretion of urea (and total nitrogen) and proteins in food - 720
9. Action of epinephrin - _ 720
10. Measurement of the heat given off in respiration - - 721
CONTENTS xxiii
CHAPTERS XIII. AND XIV.
PAGE
1. Difference of make and break induction shocks - - 807
2. Stimulation by the voltaic current - - 810
3. Ciliary motion - 811
4. Direct excitability of muscle — curara - - - 811
5. Graphic record of ' twitch ' - - 811
6. Influence of temperature on the muscle-curve - - 813
7. Influence of load on the muscle-curve - - 813
8. Influence of fatigue on the muscle-curve - 813
9. Seat of exhaustion in fatigue of the muscle-nerve preparation 813
10. Influence of veratrine on muscular contraction - 814
11. Measurement of the latent period of muscular contraction - 815
12. Summation of stimuli - - - 816
13. Superposition of contractions - - 816
1 1. Composition of tetanus - 816
15 Contraction of smooth muscles - - - 817
1 6 Velocity of the nerve-impulse - - - - 818
17. Chemistry of muscle - - - 819
1 8. Reaction of muscle in rest, activity, and rigor • - 820
CHAPTER XV.
1. Galvani's experiment - .... 842
2. Contraction without metals - .... 842
3. Secondary contraction - - 842
4. Demarcation and action currents with capillary electrometer 842
5. Action current of the heart - 844
6. Electrotonus - 844
7. Paradoxical contraction - 844
8. Alterations in excitability and conductivity produced in nerve
by a voltaic current - 844
9. Formula of contraction - 845
10. Formula of contraction for (human) nerves in situ - 846
11. Ritter's tetanus - - 846
CHAPTER XVI.
1 . Section and stimulation of nerve-roots •* 994
2. Reflex action in the ' spinal ' frog - - 995
3. Reflex time - - 995
4. Inhibition of the reflexes - 996
5. Spinal cord and muscular tonus - 996
6. Spinal cord and tonus of the bloodvessels • - 996
7. Action of strychnine - ...... 996
8. Mammalian spinal preparation - 996
9. Decerebrate cat preparation ----- 998
10. Swallowing reflex •« 1000
xxiv CONTENTS
PAGE
11. Reflex postural tonus .... IQOC
12. Reflexes in man - - 1000
13. Excision of cerebral hemispheres in the frog - - 1000
14. Excision of cerebral hemispheres in the pigeon - 1001
15. Stimulation of the motor areas in the dog - - 1001
CHAPTER XVIII.
1. Dissection of the eye - - 1101
2. Formation of inverted image on the retina - 1102
3. Helmholtz's phakoscope - 1102
4. Schemer's experiment - 1103
5. Kuhne's artificial eye - - - 1104
6. Astigmatism (ophthalmometer) - 1105
7. Spherical aberration - - 1106
8. Chromatic aberration - - 1106
9. Measurement of the field of vision - - noo
;o. Mapping the blind spot - noy
EX. The yellow spot - 1107
12. Ophthalmoscope - - 1108
13. Retinoscopy - - 1109
14. Pupillo-dilator and constrictor fibres - - - - mo
15. Colour-mixing - - - . _ -mi
1 6. After-images - - --mi
17. Retinal fatigue - . IIXI
18. Visual acuity - - . mi
19. Colour-blindness - - - _ . -1112
20. Talbot's law - - - - - . -1113
21. Purkinje's figures . . m?
22. Relation of pitch and vibration frequency - ... - 1113
23. Beats . - 1113
24. Sympathetic vibration . . . -1113
25. Galton's whistle - - . .
26. Cranial conduction of sound - - . .
27- Taste - ..... x
28. Smell - ... . I1I4
29. Touch and pressure - - - - . -1114
30. Temperature sensations - . - . -1115
31- Pa^ -
CHAPTER XIX.
1. Contractions of isolated uterine rings - . . - 1147
2. Comparison of changes of tone produced in uterus segments by
different concentrations of adrenalin
Partition of adrenalin between serum and corpuscles - 1149
A MANUAL OF PHYSIOLOGY
CHAPTER I
INTRODUCTION
LIVING matter, whether it is studied in plants or in animals, has
certain peculiarities of chemical composition and structure, but
especially certain peculiarities of action or function, which mark it
off from the unorganized material of the dead world around it.
Chemical Composition of Living Matter. — Although we cannot
analyze the living substance as such, we can to a certain, but
limited, extent reconstruct it, so to speak, from its ruins. When
subjected to analytical processes, which necessarily kill it, living
matter invariably yields bodies of the class of proteins, exceedingly
complex substances, which have approximately the following com-
position: Carbon, 51-5 to 54-5 per cent.; oxygen, 20-9 to 23-5 per
cent.; nitrogen, 15-2 to 17 per cent.; hydrogen, 6-9 to 7-3 per cent.,
with small quantities of sulphur. Nucleo-proteins, which are com-
pounds of ordinary proteins with nucleic acids, a series of sulphur-
free organic acids rich in phosphorus, are constantly met with.
Certain carbo-hydrates, composed of carbon, hydrogen, and oxygen
(the last two in the proportions necessary to form water), of which
glycogen (C6Hto05)w may be taken as a type, appear to be always
present. Fats, which consist of carbon, hydrogen, and oxygen, and
of which tristeaiin, a compound of stearic acid with glycerin, of
the formula C3H5,3(C18H3502), may be given as an example, are
often, and certain lipoids, e.g., lecithin (p. 4), are always, found.
Finally, water and certain inorganic salts, such as the chlorides and
phosphates of sodium, potassium, and calcium, are constantly present.
The Proteins. — The constitution of the protein molecule is still un-
known ; but when proteins are broken down by the action of ferments,
such as exist in gastric and in pancreatic juice, or by chemical methods
— for example, by boiling with dilute acids — the most important of
the cleavage products are various amino-acids (p. 360). It has there-
fore been suggested that proteins are built up by the linking together of
amino-acids, the different proteins differing quantitatively or quali-
tatively as regards the amino-acids present (E. Fischer). Thus serum-
albumin and egg-albumin yield no glycin or glycocoll (ammo-acetic
acid, CH2.NHa.COOH), while glycin is constantly found among the
cleavage products of serum-globulin. And while leucin (a-amino-
2 INTRODUCTION
isobutylacetic acid) is present to the extent of about 20" 5 per cent, in
the cleavage products of (horse's) serum-albumin, (hen's) egg-albumin
yields only 7' i per cent.
On the other hand, egg-albumin yields 8'i per cent, of alanin (amino-
propionic acid, C2H4.NH2.COOH), while serum-albumin yields only
2' 7 par cent. Of the aromatic amino-acids — that is, amino-acids united
to the benzene ring — phenyl-alanin (amino-propionic acid in which one
atom of H is replaced by phenyl, C6H5) is obtained to the extent of
4" 4 per cent, from egg-albumin, and a little over 3 per cent, from serum-
albumin. Ty rosin or oxyphenyl-alanin (amino-propionic acid in which
a H atom is replaced by oxyphenyl, C6H4.OH) appears to the amount
of 1*5 per cent, among the cleavage products of egg-albumin, and to
the amount of 2'i per cent, among those of serum-albumin. It is an
interesting point in this connection that gelatin, which yields i6'5 per
cent, of glycin, yields no tyrosin at all; tryptophane, an aromatic
amino-acid still more complex than tyrosin, is also absent. These facts
afford an explanation of certain colour reactions of proteins long known
empirically, but only recently understood (p. 8). The process by which
the protein molecule is thus decomposed is called hydrolysis — that is,
the molecule takes up water, and then splits into smaller molecules.
The hydrolysis occurs in various stages, bodies like acid- or alkali-
albumin (meta- or infra-proteins) being first formed, then proteoses,
then peptones. The peptones are further split into bodies containing
a relatively small number of amino-acids linked together. These bodies
are called polypeptides, which finally are decomposed so as to yield the
individual amino-acids, also called in this connection the peptides or
monopeptides, the " building-stones " out of which the protein molecule
is constructed. The inverse process can also be carried on to a certain
extent, and Fischer has taken an important step towards the eventual
synthesis of proteins by showing how polypeptides of increasing com-
plexity can be built up by linking amino-acids together. When two
amino-acids are so united, the resulting compound is called a dipeptide ;
with three amino-acids we get tripeptides, etc. Still more complicated
polypeptides may thus be formed in the laboratory, which give some of
the characteristic reactions of peptones.
The numerous substances included in the group of proteins may be
classified as follows, beginning with the simplest :
1. Protamins, such as the bodies called salmin and sturin present in
fish-sperm.
2. Histones, bodies separated from blood-corpuscles. Globin, the
protein constituent of haemoglobin, is one of them. Unlike the other
groups of proteins, they are precipitated by ammonia.
3. Albumins.
4. Globulins.
5. Sclero-proteins or albuminoids, such as gelatin and keratin.
6. Phospho-proteins, including such substances as vitellin, a body
obtainable from egg-yolk, and caseinogen, the chief protein of milk.
They are rich in phosphorus, but are to be distinguished from nucleo-
proteins, which also contain a relatively large amount of phosphorus,
by the fact that they do not yield the purin bases, the characteristic
products of the decomposition of nucleo-proteins.
7. Conjugated proteins, substances in which the protein molecule is
united to another constituent, usually spoken of as a ' prosthetic ' group.
Thus the nucleo-proteins consist of protein united with nucleic acid,
the chromo -proteins (e.g., haemoglobin) of protein united with a pig-
ment, and the gluco-proteins (e.g., mucin) of protein united with a
carbo-hydrate group.
CHEMICAL COMPOSITION OF LIVING MATTER 3
.Among the derivatives of proteins, the most important are those
already mentioned as being produced in protein-hydrolysis, viz. :
(a) Meta -proteins.
(6) Proteoses, including albumose, the proteose derived from albu-
min; globulose, that derived from globulin; gelatose, that derived from
gelatin, etc. The proteoses may be further subdivided, according to
the order in which they are formed in digestion into proto-proteoses,
hetero-proteoses, and deutero-proteoses.
(c) Peptones.
(d) Polypeptides. The majority of these are artificial products,
formed by the synthesis of amino-acids, although some can be obtained
from proteins by hydrolysis. Only a few of those hitherto prepared
give the biuret test.
However formidable the above list may appear to the student, it
gives an inadequate idea of the extreme complexity of the protein class
and its richness in individuals. For, apart from the fact that the list
has been purposely left incomplete, especially as regards the numerous
vegetable proteins, there is the best evidence that proteins of the same
name from different animal species have certain properties which dis-
tinguish them from each other. The serum-albumins can be crystal-
lized much more easily in some animals than in others. The same is
conspicuously true of the haemoglobins, which differ also in certain
animals in the relative proportion of sulphur and iron in the molecule,
as well as in the crystalline form. Even when no chemical or physical
differences have as yet been made out, proteins of the same name from
the blood or organs of different species show notable ' specific ' differ-
ences when subjected to certain biological tests (see, e.g., the paragraph
on Precipitins, p. 31 ; and that on Anaphylaxis, p. 32).
Carbo-Hydrates. — The most important carbo-hydrates in their physio-
logical relations are dextrose, levulose, galactose, lactose, maltose,
sucrose (cane-sugar), starch, and glycogen. As regards their chemical
constitution, the simplest carbo-hydrates are aldehydes or ketones —
that is, the first oxidation products of primary and secondary alcohols
respectively. Thus dextrose is the aldehyde of sorbite, a hexatomic
alcohol (an alcohol containing six OH groups), while levulose is the
ketone of the isomeric alcohol called mannite, and galactose the alde-
hyde of the isomeric alcohol called dulcite. The sugars containing six
carbon atoms are termed hexoses. They include dextrose, levulose,
and galactose. The empirical formula of these three simple sugars (or
monosaccharides) is the same (CjHjaOg), but, owing to the different
arrangement of the atoms or groups of atoms, they have each their
characteristic properties by which they can be easily distinguished.
For example, dextrose rotates the plane of polarization to the right,
levulose to the left. By the union or ' condensation ' of two molecules
of a monosaccharide, with loss of a molecule of water, a disaccharide is
formed. Cane-sugar, maltose, and lactose, all with the same empirical
formula, (C^H^On), are disaccharides. Cane-sugar yields on hydro-
lysis a mixture of equal parts of dextrose and levulose ; lactose, a mix-
ture of dextrose and galactose ; while maltose is converted into dextrose.
By the condensation of more than two molecules of monosaccharide
polysaccharides are formed, such as starch, dextrin, and glycogen. The
exact molecular weights of these substances are unknown. Their
general formula can be written (C6H10O5)», where n represents the
number of monosaccharide molecules condensed to form the poly-
saccharide, in the case of starch probably some hundreds.
Fats and Lipoids. — The fats are compounds of higher fatty acids
with glycerin (glycerin esters). The ordinary body-fat consi:ts of a
4 INTRODUCTION
mixture of three neutral fats (palmitin, stearin, and olein) which differ
both chemically and physically from each other — e.g., in melting-point
and in the so-called iodine value, the number which represents the
amount of iodine taken up from a standard solution. Olein melts at
-5° C., palmitin at 45° C., and stearin at a still higher temperature.
It is, therefore, the presence of olein which keeps the body-fat liquid
at the temperature of the body. The fats are soluble in ether, in hot
alcohol, and in many other liquids, but insoluble in water. Besides
the ordinary fats, the tissues and liquids of the body contain phospha-
tides, a group of compounds which stand in close relation to the fats,
but differ in containing phosphoric acid and nitrogenous bases. The
most important representative of this group is lecithin (C42H84NPO9),
a fat-like compound which yields on decomposition, in addition to
glycerin and a fatty acid, phosphoric acid and a nitrogen-containing
substance called cholin (p. 366). Lecithin, though found in all cells, is
especially abundant in nervous tissues. It is associated with choles-
terin and with other substances which, like lecithin and cholesterin,
are soluble in ether and similar solvents of fat. For this reason these
substances are often grouped together as lipoids, although some of
them are chemically different from fat. Cholesterin, for instance, is an
alcohol. Although usually present only in small amount, the lipoids
play a very important part in the structure and in the economy of the
cell.
Structure of Living Matter — The Cell.* — Bioplasm is the name
given to the living matter of cells. The portion of the bioplasm
differentiated as the nucleus is distinguished by the term karyo-
plasm, and the portion outside the nucleus by the term protoplasm
or cytoplasm. Protoplasm, when examined in its most primitive
undifferentiated condition in such cells as the amceba or the white
blood-corpuscles, appears on first view a homogeneous, structureless
mass, except for certain granules embedded in it, and consisting
either of products formed by its activity or of food materials. But
even here more careful study reveals a certain complexity of struc-
ture. At the very least, an external layer, or ectoplasm, can be dis-
tinguished from the interior mass, or endoplasm. There is reason
to believe that even where no histological demonstration of an
ectoplasmic layer or a definite envelope is possible, the surface of
the cell is physiologically different from its interior. In many cells
the protoplasm presents the appearance of a honeycomb or net-
work, with granules usually situated at the nodes, and holding in
its vesicles or meshes a fluid, perhaps containing pabulum, from
which the waste of the living framework is made good, or material
upon which it works, and which it is its business to transform.
Some observers, however, maintain that the network is an artificial
appearance produced by the precipitation of the colloid constituents
of the protoplasm by the fixing reagent, or even by the coagulative
processes associated with the act of dying, and that the unaltered
living substance is a homogeneous fluid or jelly. It is known that
* Space permits only the slightest sketch of this subject here. For de-
tailed information the student is referred to textbooks of histology.
STRUCTURE OF LIVING MATTER 5
changes of reaction occur when the living substance dies, and slight
changes of reaction, i.e., changes in the relative concentration of
hydrogen ions (H+) and hydroxyl ions (OH-), can bring about
similar precipitates in colloid solutions. Nevertheless in some cells
a certain differentiation in the structure of the protoplasm can be
seen during life and before the addition of any reagent, and in such
cases there can be no doubt that the structural details pre-exist
and are not arte-facts. In certain respects protoplasm behaves
like a liquid, and in others like a solid, a peculiarity which is un-
doubtedly associated with the fact that its chief constituents exist
in the colloid state, as experiments with such substances as gelatin
and agar have shown. In building up our typical cell we start with
a piece of protoplasm. Somewhere in the midst of this we find a
body which, if not absolutely different in kind from the protoplasm
of the rest of the cell or cytoplasm, is yet marked off from it by very
definite morphological and chemical characters.
This is the nucleus, generally of round or oval shape, and bounded
by an envelope. Within the envelope lies a second network of
fine threads, which do not themselves stain with nuclear dyes such
as hgematoxylin. But in or on these ' achromatic ' filaments lie
small, highly refractive particles, staining readily and deeply with
dyes, and therefore described as consisting of chromatin. This chro-
matin is either made up of nucleins (conjugated proteins particu-
larly rich in nucleic acid, and therefore in phosphorus), or yields
nucleins by its decomposition; and it seems to owe its affinity for
certain staining substances to the presence of nucleic acid. The
meshes of the nuclear reticulum contain a semi-fluid material,
which does not readily stain. The nucleus is distinguished from
the cytoplasm, even as regards its inorganic constituents, by the
absence of potassium.* Besides the nucleus, another much smaller
structure, the centrosome, is differentiated from the protoplasm
of many cells. This is a minute dot staining deeply with such dyes
as heematoxylin, and generally situated near the nucleus. Sur-
rounding it is a clear area, the attraction sphere, in and beyond
which fine fibrils radiate out into the cytoplasm. Both the attrac -
tion sphere and the nucleus play an important part in division of
the cell by the process known as karyokinesis, or mitosis, or in-
direct division, which is by far the most common mode.
When the nucleus is about to divide, the chromatin granules
arrange themselves into one or more coiled filaments or skeins,
which then break up into a number of separate portions called
* This has been shown microchemically. The potassium is precipitated
by a solution of hexanitrite of sodium and cobalt as orange-yellow crystals of
the triple salt, hexanitrite of potassium, sodium, and cobalt. Where very
minute traces of potassium are present, ammonium sulphide must be added,
after washing out the excess of the cobalt reagent. Black cobalt sulphide is
thus formed from the triple salt (Macallum, Frontispiece).
6 INTRODUCTION
chromosomes. These undergo a remarkable series of transforma-
tions, leading eventually to the segregation of the nuclear chromatin
in two separate daughter nuclei, each surrounded by a portion of
the original cytoplasm. Apart from its role in the division, and
therefore in the multiplication, of the cell, the nucleus is now known
to exert an influence perhaps not less important upon those chemical
changes in the cytoplasm which are necessary for its normal nutri-
tion and function.* It is doubtful whether any portion of proto-
plasm can permanently survive the loss of its nuclear material. It
must be remembered, however, that nuclear material may some-
times be present in diffuse form in cells which do not show a nucleus
in the histological sense.
When we carry back the analysis of an organized body as far as
we can, we find that every organ of it is made up of cells, which
upon the whole conform to the type we have been describing,
although there are many differences in details. Some organisms
there are, low down in the scale, whose whole activity is confined
within the narrow limits of a single cell. The amoeba sets up in life
as a cell split off from its parent. It divides in its turn, and each
half is a complete amoeba. When we come a little higher than the
amoeba, we find organisms which consist of several cells, and
' specialization of function ' begins to appear. Thus the hydra, the
' common fresh- water polyp ' of our ponds and marshes, has an outer
set of cells, the ectoderm, and an inner set, the endoderm. Through
the superficial portions of the former it learns what is going on in
the world; by the contraction of their deeply placed processes it
shapes its life to its environment. As we mount in the animal
scale, specialization of structure and of function are found con-
tinually advancing, and the various kinds of cells are grouped
together into colonies or organs. In some organs and tissues the
bond of union is simple juxtaposition and similarity of function of
the constituent cells. But in others the union is protoplasmic, pro-
cesses of the cytoplasm actually passing from cell to cell. This is
seen in certain epithelial tissues, and conspicuously in the cardiac
muscle.
The Functions of Living Matter. — The peculiar functions of living
matter as exhibited in the animal body will form the subject of the
main portion of this book ; and we need only say here : (i) That in all
living organisms certain chemical changes go on, the sum total of
which constitutes the metabolism of the body. These may be
divided into (a) integrative or anabolic changes, by which complex
substances (including the living matter itself) are built up from
* According to Hertwig, a precursor of chromatin, ' prochromatin,' a sub-
stance without characteristic staining reaction, is formed in the cytoplasm,
taken up by the nucleus, and there elaborated into chromatin. From the
nucleus chromatin and its derivatives return to the cytoplasm to be used in
its function.
FUNCTIONS OF LIVING MATTER 7
simpler materials; and (b) disintegrative or katabolic changes, in
which complex bodies (including the living substance) are broken
down into comparatively simple products. In plants, upon the
whole, it is integration which predominates; from substances so
simple as the carbon dioxide of the air and the nitrates of the soil
the plant builds up its carbo-hydrates and its proteins. In animals
the main drift of the metabolic current is from the complex to the
simple; no animal can construct its own protoplasm from the
inorganic materials that lie around it; it must have ready-made
protein in its food. But in all plants there is some disintegration;
in all animals there is some synthesis. The progress of biochemistry
in recent years has indeed shown that the synthetic powers of
animal cells have been greatly underestimated. (2) The living sub-
stance is excitable — that is, it responds to certain external im-
pressions, or stimuli, by actions peculiar to each kind of cell.
(3) The living substance reproduces itself. All the manifold activities
included under these three heads have but one source, the trans-
formation of the energy of the food. It is not, however, upon the
whole, peculiarities in food, but in molecular structure, that underlie
the peculiarities of function of different living cells. A locomotive
is fed with coal; a steam-pump is fed with coal. The one carries
the mail, and the other keeps a mine from being flooded. Wherein
lies the difference of action ? Clearly in the build, the structure of
the mechanism, which determines the manner in which energy shall
be transformed within it, not in any difference in the source of the
energy. So one animal cell, whi.-a it is stimulated, shortens or con-
tracts; another, fed perhaps with the same food, selects certain
constituents from the blood or lymph, and passes them through its
substance, changing them, it may be, on the way ; and a third sets
up impulses which, when transmitted to the other two, initiate the
contraction or secretion. In the living body the cell is the machine ;
the transformation of the energy of the food is the process which
' runs ' it. The structure and arrangement of cells and the steps
by which energy is transformed within them sum up the whole of
biology.
PRACTICAL EXERCISES ON CHAPTER I.
Reactions of Proteins.
i. General Reactions of Proteins.— Egg-albumin may be taken as a
type. Prepare a solution of it by adding water to white of egg, which
consists mainly of egg-albumin with a little globulin. In breaking the
egg, take care that none of the yolk gets mixed with the white. Snip
the white up with scissors in a large capsule, then add ten or fifteen
times its volume of distilled water. The solution becomes turbid from
the precipitation of traces of globulin, since globulins are insoluble in
distilled water. Stir thoroughly, strain through several layers of muslin,
and then filter through paper.
8 INTRODUCTION
Colour Reactions.
(1) Add to a little of the solution in a test-tube a few drops of strong
nitric acid. A precipitate is thrown down, which becomes yellow on
boiling. Cool, and add strong ammonia; the colour changes to orange
(xantho-proteic reaction). The reaction depends upon the presence of
aromatic groups in the protein (in phenylalanin, tyrosin, tryptophane,
oxytryptophane), which are converted into nitro-compounds.
(2) To a third portion add a drop or two of very dilute cupric sulphate
and excess of sodium or potassium hydroxide ; a violet colour appears
(Piotrowski' s test). Peptones and proteoses (albumoses) give a pink
(biuret reaction).* See p. 458.
(3) To another portion add Millon's reagent ;f a white precipitate
comes down, which is turned reddish on boiling. If only traces of
protein are present, no precipitate is caused, but the liquid takes on a
red tinge. The reaction is due to tyrosin. It is given by all aromatic
substances which contain the group C6H6 with at least one H replaced
by OH, i.e., the hydroxyphenyl group C6H4OH.
(4) Adamkiewicz's Reaction (Hopkins' s modification). — To a small
quantity of the albumin solution add the same bulk of dilute glyoxylic
acid.J Mix, and to the mixture add an equal volume of strong pure
sulphuric acid. A purple colour is obtained. The substance in the
protein molecule which gives the reaction is tryptophane (p. 360).
(5) The Formaldehyde Reaction. — Add to the albumin solution a few
drops of a very dilute solution of formaldehyde (i : 2,500), and then
allow some strong (commercial) sulphuric acid to run from a pipette
into the bottom of the test-tube. A purple ring appears at the surface
of contact. This reaction depends on the presence of tryptophane in
the protein.
Precipitation Rtactiontt
(6) Acidify another portion strongly with acetic acid, and add a few
drops of a solution of potassium ferrocyanide. A white precipitate is
obtained. Peptones do not give this reaction.
(7) Heat a portion to 30° C. on a water-bath. Saturate with crystals
of ammonium sulphate; the albumin is precipitated. Filter, and test
the filtrate for proteins by (2). None, or only slight traces, will be
found. The sodium hydroxide must be added in more than sufficient
quantity to decompose all the ammonium sulphate. It will be best to
add a piece of the solid hydroxide. Peptones are not precipitated by
ammonium sulphate, but all other proteins are.
(8) Add alcohol to a small quantity of the solution. The protein is
* The reaction is also given, although more faintly, with the hydroxides of
lithium, strontium, and barium. It is given by all substances containing at
least two CONH2 groups attached to one another (as in oxamide), or to the
nitrogen atom (as in biuret) , or to the same carbon atom.
f Millon's reagent consists of a mixture of the nitrates of mercury with
nitric acid in excess, and some nitrous acid. To make it, dissolve mercury in
its own weight of strong nitric acid, and add to the solution thus obtained
twice its volume of water. Let it stand for a short time, and then decant the
clear liquid, which is the reagent.
J A solution containing glyoxylic acid in the requisite strength can be
prepared by treating half a litre of a saturated solution of oxalic acid with
40 grammes of 2 per cent, sodium amalgam in a tall cylinder. When all the
hydrogen has been evolved, the solution is filtered, and diluted with twice its
volume of water. Oxalic acid and sodium binoxalate are also present in the
solution.
PRACTICAL EXERCISES g
precipitated. It can be redissolved at first, but rapidly becomes in-
soluble.
2. Special Reactions of Certain Proteins — (i) Heat-Coagulable Pro-
teins : (a) Albumins. — (a) Heat a little of the solution of egg-albumin in
a test-tube; it coagulates. With another sample determine the tem-
perature of coagulation, first very slightly acidulating with a 2 per cent,
solution of acetic acid.
To determine the Temperature of Coagulation. — Support a beaker by
a ring which just grips it at the rim. Nearly fill the beaker with water,
and slide the ring on the stand till the lower part of the beaker is im-
mersed in a small water-bath (a tin can will do quite well). In this
beaker place a test-tube, and in the test-tube a thermometer, both sup-
ported by rings or clamps attached to the same stand. Put into the
test-tube at least enough of the albumin solution to completely cover
the bulb of the thermometer, and heat the bath, stirring the water in
the beaker occasionally with a feather or a splinter of wood, or a glass
rod, the end of which is guarded with a piece of indiarubber tubing.
Note the temperature at which the solution becomes turbid, and then
the temperature at which a distinct coagulum or precipitate is formed.
Repeat with the unacidulated albumin solution.
(£) A similar experiment may be performed with serum-albumin
obtained as on p. 65.
(b) Globulins. — Use serum- globulin (p. 65), or myosinogen (p. 819).
Fibrinogen is also a globulin, but cannot easily be obtained in quantity.
Verify the following properties of globulins:
(a) They coagulate on heating.
(£) They are insoluble in distilled water (p. 65).
(7) They are precipitated by saturation with magnesium sulphate or
sodium chloride (p. 65).
They give the general protein tests (i) to (8).
Both the heat-coagulated proteins and such proteins as the solid
fibrin which is formed from fibrinogen in the clotting of blood give such
of the general protein tests, (i), (2), (3) (p. 8), as with suitable modifica-
tions can be instituted on solid substances. Thus, in performing (2), a
flake of fibrin or a small piece of the boiled egg-white should be soaked
for a few minutes in a dilute solution of cupric sulphate. Then the
excess of the cupric sulphate should be poured off, and sodium hydroxide
added, when the coagulated protein will become violet. Heat-coagu-
lated proteins are insoluble in water, weak acids and alkalies, and saline
solutions ; fibrin is slightly soluble in the latter.
(2) Gelatin. — Add some pieces of gelatin to cold water in a test-tube.
It does not dissolve. Immerse the tube in a boiling water-bath till the
gelatin goes into solution. Then cool the test-tube under the tap; the
solution sets into a jelly. On heating it redissolves.
Try the general protein reactions (p. 8) on a dilute solution. In
Piotrowski's test a violet colour is obtained. The tests which depend
on the presence of tyrosin or tryptophane are not given by a solution
of pure gelatin, since these ammo-acids are absent from the gelatin
molecule. Commercial gelatin may give a slight reaction due to
traces of other proteins.
3. Reactions of Certain Derivatives of Native Proteins — (i) Meta-
Proleins : (a) Acid-Albumin. — To a solution of egg-albumin add a little
o-4 per cent, hydrochloric acid, and heat to about body temperature —
say 40° C. — for a few minutes. Acid -albumin is formed. It can be
produced from all albumins and globulins by the action of dilute acid.
Make the following tests :
(a) Add to a portion of the solution in a test-tube a few drops of a
to INTRODUCTION
solution of litmus; the colour becomes red. Now add drop by drop
sodium carbonate or dilute sodium hydroxide solution till the tint just
begins to change to blue. A precipitate of acid -albumin is thrown
down . Add a little more of the alkali, and the precipitate is redissolved.
It can be again brought down by neutralizing with acid.
(/3) Heat a portion of the solution to boiling; no precipitate is formed .
(y) Add strong nitric acid ; a precipitate appears, which dissolves on
heating, and the liquid becomes yellow.
(b) Alkali- albumin. — To a solution of egg-albumin add a little sodium
hydroxide, and heat gently for a few minutes. Alkali-albumin is
produced. It can be derived by similar treatment from any albumin
or globulin.
(a) Neutralize, after colouring with litmus solution, by the addition
of dilute hydrochloric or acetic acid. Alkali-albumin is precipitated
when neutralization has been reached. It is redissolved in excess of
the acid.
(/3) To another portion of the solution of alkali-albumin add a few
drops of sodium phosphate solution, then litmus, and then dilute acid
till the alkali-albumin is precipitated. More of the dilute acid should
now be required to precipitate the alkali-albumin, since the sodium
phosphate must first be changed into acid sodium phosphate.
(y) On heating the solution of alkali-albumin there is no coagulation.
(2) Proteoses. — For preparation and reactions, see p. 458. They
differ from albumins and globulins in not being coagulated by heat, and
from meta -proteins in not being precipitated by neutralization. They
are soluble (with the exception of hetero-albumose) in distilled water,
and are not precipitated by saturation of their solutions with mag-
nesium sulphate or sodium chloride. Saturation with ammonium sul-
phate precipitates them. With a solution of ' commercial peptone,'
which consists chiefly of albumoses, and contains only a little true
peptone, perform the following tests:
(a) Boil the slightly acidulated solution; there is no coagulation.
(/3) Biuret reaction, p. 8.
(y) -
(y) To a portion of the solution add its own volume of saturated
ammonium sulphate solution. The primary albumoses (proto- and
hetero-albumose) are precipitated. Filter. Add a drop of sulphuric
acid to the filtrate and saturate it with ammonium sulphate crystals.
The secondary or deutero-albumoses are precipitated. Filter. The
filtrate stilljcontains peptones. Use it for (3).
(3) Peptones. — For preparation and tests, see p. 459. They differ
from heat-coagulable proteins and meta-proteins in the same way as
proteoses, and they differ from proteoses in not being precipitated by
ammonium sulphate. On the filtrate from (2) perform the biuret test,
as described in (7), p. 8; and note that the pink colour is the same as
that given by proteoses.
Carbo-Hydrates.
i. Glucose or Dextrose. — Make a solution of dextrose in water, and
apply to it Trommer's test for reducing sugar. Put some of the dextrose
solution in a test-tube, then a few drops of cupric sulphate, and then
excess of sodium or potassium hydroxide. The blue precipitate of
cupric hydroxide which is first thrown down is immediately dissolved
in the presence of dextrose and many other organic substances. Now
boil the blue liquid, and a yellow or red precipitate (cuprous hydroxide
or oxide) is formed.
PRACTICAL EXERCISES n
2. Cane-Sugar. — Perform Trommer's test with a sample of a solution.
A blue liquid is obtained, which is not changed on boiling. Now put
the rest of the solution in a flask. Add ^th of its bulk of strong hydro-
chloric acid, and boil for a quarter of an hour. Again perform Trom-
mer's test. Remember that excess of alkali must be present after the
acid is neutralized. The test now shows much reducing sugar. The
cane-sugar has been ' inverted ' — i.e., changed into a mixture of
dextrose and levulose.
3. Starch. — (i) Cut a slice from a well-washed potato ; take a scraping
from it with a knife, and examine with the microscope. Note the starch
granules with their concentric markings, using a small diaphragm.
Run a drop of dilute iodine solution under the cover-slip, and observe
that the granules become bluish. Examine also with a polarization
microscope. (2) Rub up a little starch in a mortar with cold water,
then add boiling water and stir thoroughly. Decant into a capsule or
beaker, and boil for a few minutes. After the liquid has cooled, perform
the following experiments:
(a) Add a few drops of iodine solution to a little of the thin starch
mucilage in a test-tube. A blue colour is produced, which disappears
on heating, returns on cooling, is bleached by the addition of a little
sodium hydroxide, and restored by dilute acid.
(b) Test the starch solution for reducing sugar by Trommer's test.
If none is found, boil some of the mucilage with a little dilute sulphuric
acid in a flask for twenty minutes, and again perform Trommer's test.
Abundance of reducing sugar will now be present.
4. Dextrin. — Dissolve some dextrin in boiling water. Cool. Add
iodine solution to a portion ; a reddish-brown (port- wine) colour results,
which disappears on heating. As a control, the same amount of iodine
should be added to an equal quantity of water in another test-tube.
The colour returns on cooling. The colour is also bleached by alkali,
restored by acid. Excess of iodine should be added for the bleaching
experiment (i.e., more than enough to give the maximum depth of tint).
If too little iodine has been added, there may be no restoration of the
colour by the acid. The addition of a little more iodine to the acid
solution will then cause the port-wine colour to return, and this may
be again bleached by alkali, and will now be restored by acid.
5. Glycogen. — See p. 715.
6. Molisch 's Test for Carbo-Hydrates. — This is a general test for carbo-
hydrates. It is also given by proteins which contain a carbo-hydrate
group. Put a drop of dextrose solution in a test-tube. Add a drop
of a 10 per cent, solution of a-naphthol in methyl alcohol, and then
o'5 c.c. of water. Then cautiously allow I c.c. of pure concentrated
sulphuric acid to run under the mixture, and shake gently. A violet or
reddish colour appears.
Fats.
1. Take a little lard or olive-oil, and observe that fat is soluble in
ether or warm alcohol, but not in water. Put a drop of the ethereal
solution of fat on a piece of paper, and note that it leaves a greasy stain.
2. Put a little alcohol in a test-tube, and then a drop of phenol-
phthalein solution and a drop or two of dilute sodium hydroxide to give
the solution a red colour. Add a few drops of an ethereal solution of
the lard or olive-oil. If the red colour persists, the fat is neutral; if it
disappears, the fat contains free fatty acids.
3. Saponification. — Melt some lard in a porcelain dish, and pour it
12 INTRODUCTION
into an alcoholic solution of potassium hydroxide previously heated on
a water-bath nearly to boiling. Mix well, and keep the mixture gently
boiling on the bath till saponification is complete. This only takes a
short time. Remove a little of the soap solution, and drop it into dis^
tilled water in a test-tube. If unsaponified fat is present, it will rise to
the top as drops of oil. In this case boiling should be continued. If
all the fat has been saponified, the soap solution will mix with the
water and no oil-drops will separate.
4. Fatty Acids. — Heat some 20 per cent, sulphuric acid in a small
flask nearly to boiling, and drop into it some of the soap obtained in 3.
The fatty acids separate put and rise to the top as an oily layer. Cool,
skim off the fatty acid, and wash it with distilled water till the wash-
water is no longer acid.
(a) Dissolve a little of the washed fatty acid in ether. Add a few
drops of an alkaline solution of phenolphthalein to a few c.c. of water
in a test-tube. Drop into this the ethereal solution of fatty acid. The
red colour is discharged.
(6) Put a small portion of the fatty acid on a glass slide resting on a
piece of white paper. Place on it a drop or two of a i per cent, solution
of osmic acid (osmium tetroxide). The osmic acid is reduced to a lower
oxide (which is black) by the action of oleic acid present in the fatty
acid mixture, which abstracts some of the oxygen. Any. fat which
contains olein or oleic acid, as body-fat does, is therefore blackened by
osmic acid.
(c) Add to a portion of the fatty acid some sodium hydroxide solution,
and warm. Sodium soap is formed. Add warm water and shake up.
A lather is produced. Keep the soap solution for 6. Keep a little of
the fatty acid for 5 (b) and 6 (b).
5. Glycerin. — (a) Add to a little glycerin in a dry test-tube a few
crystals of potassium bisulphate (KHSO4), and heat over the free flame.
Acrolein is given off, which is recognized by its pungent odour, and by
blackening a piece of filter-paper moistened with ammoniacal silver
nitrate solution, and held over the mouth of the test-tube. The paper
is blackened owing to the reducing action of the vapour on the silver
nitrate.
(b) Repeat this test with lard, and with a portion of the fatty acid
from 4. Acrolein will be given off by the lard because glycerin is con-
tained in neutral fat, but not by the fatty acid if it has been properly
separated from the glycerin.
6. Emulsification. — (a) Take three test-tubes and label them A, B,
and C. Put a few c.c. of water in A, a solution of soap in B, and a
dilute solution of sodium carbonate or sodium hydroxide in C. To each
add a few drops of fresh olive -oil and shake . An emulsion will be formed
in B, but not in A. Probably there will be some emulsification in C also,
owing to the presence in the oil of some fatty acid, which forms soap
with the alkali. But if the oil is free from fatty acid, no emulsion will
be formed.
(b) Repeat (a) with rancid olive-oil, which contains much fatty acid,
or with fresh olive-oil to which some of the fatty acid obtained in 4 has
been added. A good emulsion will be produced in C as well as in B.
7. Melting-Point of Fat. — Put into a very narrow test-tube or a short
piece of narrow glass tubing some finely divided mutton fat, freed, as
far as possible, from connective tissue. Fasten the test-tube on to the
bulb of a thermometer with a rubber band, and immerse the ther-
mometer and tube in a beaker filled with water and standing on a water-
bath, which is gradually heated. Observe the temperature at which
the fat melts. Repeat the experiment with hog's lard and dog's fat.
PRACTICAL EXERCISES 13
SCHEME FOR TESTING A SOLUTION FOR THE MORE COMMON
PROTEINS AND PROTEIN-DERIVATIVES, AND FOR CARBO-
HYDRATES
1. Note the reaction, and whether the liquid is coloured or colourless, clear
or opalescent. A reddish colour suggests blood ; opalescence suggests glyco-
gen or starch. Try one or more of the general protein tests (e.g., the xantho-
proteic or biuret). If the result is positive, proceed as in 2; if negative, pass
to 3.
2. Test for Proteins. — (i) If the reaction is acid or alkaline, neutralize with
very dilute sodium carbonate or sulphuric acid. A precipitate=acid- or
alkali-albumin, according as the original reaction is acid or alkaline. If the
original reaction is neutral, no acid- or alkali-albumin can be present in
solution. Filter off the precipitate, if any.
(2) Boil some of the nitrate from (i) (or some of the original solution if
it is neutral), acidulating slightly with dilute acetic acid. A precipitate =
albumin or globulin. Filter, and keep the nitrate.
(3) If a precipitate has been obtained in (2), (a) saturate some of the original
solution with magnesium sulphate, or half saturate it with ammonium sulphate
(i.e., add to it an equal volume of saturated ammonium sulphate solution).
If there is no precipitate, globulin is absent, and therefore the precipitate
obtained in (2) must be albumin. A precipitate =globulin. But albumin
may also be present in the solution. To see whether this is so, filter off the
globulin and boil the nitrate after acidulation with acetic acid. A precipitate
= albumin.
(b) Half saturate the filtrate from (2) with ammonium sulphate (i.e., add its
own volume of a saturated solution of the salt). A precipitate = primary
proteoses. Filter.
(c) Saturate the filtrate from (6) with ammonium sulphate crystals. A
precipitate = secondary proteoses. Filter.
(d) To the filtrate from (c) add excess of solid sodium hydroxide in small
pieces at a time. Much ammonia is given off. Allow the test-tube to stand
fifteen minutes, shaking it at intervals. Then add dilute cupric sulphate,
and if much of the sodium sulphate formed remains undissolved, add water
to dissolve it. A well-marked rose colour = peptone.
(4) If no precipitate has been obtained in (2) , the solution contains neither
albumin nor globulin. To test whether primary or secondary proteose or
peptone is present, apply (3) (b), (c), and (d).
3. Test for Carbo- Hydrates. — Use the original solution, freed from coagu-
lable proteins, if such have been found, by acidulation and boiling.
(1) Add iodine. If the solution is alkaline neutralize it before adding the
iodine. A blue colour = starch. Confirm by boiling with dilute sulphuric
acid and testing for reducing sugar. A reddish-brown colour with iodine =
glycogen or dextrin.
Glycogen gives an opalescent, dextrin a clear, solution. Glycogen is pre-
cipitated by basic lead acetate, dextrin is not (p. 715). Both are changed
into reducing sugar by boiling with dilute acid.
(2) Add to some of the original solution cupric sulphate and excess of
sodium hydroxide, and boil. Yellow or red precipitate = reducing sugar.
(3) If (i) and (2) are negative, boil some of the liquid with one-twentieth
of its volume of strong hydrochloric acid for fifteen minutes, and test as in (2).
A red or yellow precipitate indicates that a disaccharide like cane-sugar was
originally present, and has been inverted.
CHAPTER II
THE CIRCULATING LIQUIDS OF THE BODY
IN the living cells of the animal body chemical changes are con-
stantly going on; energy, on the whole, is running down; complex
substances are being broken up into simpler combinations. So long
as life lasts, food must be brought to the tissues, and waste products
carried away from them. In lowly forms like the amoeba these
functions are performed by interchange at the surface of the
animal without any special mechanism; but in all complex organ-
isms they are the business of special liquids, which circulate in
finely branching channels, and are brought into close relation at
various parts of their course with absorbing organs, with eliminating
organs, and with the tissue elements in general.
In the higher animals three circulating liquids have been dis-
tinguished: blood, lymph, and chyle. But it is to be remarked
that chyle is only lymph derived from the walls of the alimentary
canal, and therefore, during digestion, containing certain freshly-
absorbed constituents of the food; while both ordinary lymph and
chyle ultimately find their way into the blood, and are in their turn
recruited from it. The blood contains at one time or another
everything which is about to become part of the tissues, and every-
thing which has ceased to belong to them. It is at once the
scavenger and the food-provider of the cell. But no bloodvessel
enters any cell;* and if we could unravel the complex mass of
tissue elements which essentially constitute what we call an organ,
we should see a sheet of cells, with capillaries in very close relation
to them, but everywhere separated from them by a thin layer of
lymph. And to describe in a word the circulation of the food
substances we may say that the blood feeds the lymph, and the lymph
feeds the cell.
SECTION I. — MORPHOLOGY OF THE BLOOD.
The blood consists essentially of a liquid part, the plasma, in
which are suspended cellular elements, the corpuscles. When the
circulation in a frog's web or lung or in the tail of a tadpole is
* Fine intracellular canaliculi, communicating with the blood-capillaries,
and probably performing a nutritive function, since they seem to contain
blood -plasma, have been described by Schafer and others in the liver cells.
14
THE BLOOD-CORPUSCLES 15
examined under the microscope, the bloodvessels are seen to be
crowded with oval bodies — of a yellowish tinge in a thin layer, but
in thick layers crimson- — which move with varying velocity, now
in single file, now jostling each other two or three abreast, as they
are borne along in the axis of an apparently scanty stream of
transparent liquid. Nearer the walls of the vessels, sometimes
clinging to them for a little and then being washed away again,
may be seen, especially as the blood-flow slackens, a few com-
paratively small, round, colourless cells. The oval bodies are the
red or coloured corpuscles, or erythrocytes ; the colourless elements
are the white blood-corpuscles, or leucocytes; the liquid in which
they float is the plasma (Practical Exercises, p. 193).
The Red Blood-Corpuscles, or Erythrocytes, differ in shape and
size and in other respects in different animal groups. In amphib-
ians, such as the frog and the newt, they are flattened ellipsoids
containing a nucleus, and the same
is true of nearly all the other ver-
tebrates, except mammals. In
i-
mammals they are discs, hollowed
out on both the flat surfaces, or
biconcave, and possess no nucleus.
But the red corpuscles of the llama
and the camel, although non-
i , j 11- -j i • i Fig. i. — Diagram showing Relative
nucleated, are ellipsoidal in shape, |ize of Re« corpuscles of Various
like those of the lower vertebrates. Animals.
As to size, the average diameter
in man is between 7 and 8 fj,.* In the frog the long diameter is
about 22 /j,, while in Proteus it is as much as 60 /j,, and in Amphiuma,
the corpuscles of which can be seen with the naked eye, nearly
80 ft (Frontispiece) .
As regards the structure of the red corpuscles, the most prob-
able view is that they are solid bodies, with a spongy and elastic
structureless framework, denser at the surface of the corpuscle than
in its centre, but continuous throughout its whole mass (Rollett) .
The denser peripheral layer constitutes a physiological envelope
which permits the passage of certain substances into or out of the
corpuscles, and hinders the passage of others. In the large oval
corpuscles of Necturus (see Frontispiece) the envelope can be clearly
demonstrated as a detachable membrane comparable to the mem-
brane surrounding the nucleus.
Envelope and spongework are sometimes spoken of as the stroma
of the corpuscle, in contradistinction to its most important con-
stituent, a highly complex pigment, the haemoglobin. This pigment
is not in solution as such, for its solubility is not nearly great
enough to permit this, but either in solution as a compound with
* A micro-millimetre, represented bv symbol /*, is ^-^ millimetre.
16
THE CIRCULATING LIQUIDS OF THE BODY
some other unknown substance, or more probably bound in some
solid or semi-solid combination to the stroma, and filling up the
space within the envelope in the interstices of the spongework.
Since there is good reason to believe that the haemoglobin as
obtained artificially from the corpuscles is not quite the same sub-
stance as the native blood-pigment within them, the latter is some-
times distinguished by a separate name — hsemochrome. To the
physical properties of the stroma it is usual to attribute the great
elasticity of the corpuscles — that is, the power of recovering their
original shape after distortion — for their elasticity is in no wise
impaired by the removal of the haemoglobin.
Rouleaux Formation. — When blood with disc-shaped corpuscles is
shed, there is a great tendency for the corpuscles to run together into
groups resembling rouleaux, or piles of coin. No satisfactory explana-
tion of this curious fact has yet been given.
Crenation of the corpuscles, a condition in which they become
studded with fine projections, is caused by the addition of moderately
strong salt solution, by the passage of shocks of electricity at high
potential, as from a Leyden jar, or by simple exposure to the air. Con-
centrated saline solutions, which abstract water from the corpuscles
and cause them to shrink, make the colour of blood a brighter red,
because more light is now reflected from the crumpled surfaces. On
the other hand, the addition of water renders the corpuscles spherical;
more of the light passes through them, less is reflected, and the colour
becomes dark crimson (Frontispiece).
The White Blood-Corpuscles, or Leucocytes. — The red corpuscles
are peculiar to blood. The white corpuscles may be looked upon
as peripatetic portions of the mesoderm (see Chap. XIX.), and some
of them ought not in strictness to be called blood-corpuscles. They
are more truly body corpuscles. Similar cells are found in many
situations, and wan-
der everywhere in the
spaces of the connec-
tive tissue. They pass
into the bloodvessels
with the lymph, and
may pass out of them
again in virtue of
their amoeboid power.
They consist of proto-
plasm, less differ-
entiated than that
of any other cells in
the body, and under the microscope appear as granular, colour-
less, transparent bodies, spherical in form when at rest, and
containing a nucleus, often tri- or multi-lobed. Many of the leuco
cytes of frog's blood at the ordinary temperature, and of mam-
malian blood when artificially heated on the warm stage, may be
A.
D.
Fig. 2. — Amoeboid Movement. A, B, C, D, succes-
sive changes in the form of an amoeba.
THE BLOOD-CORPUSCLES if
seen to undergo slow changes of form. Processes called pseudo-
podia are pushed out at one portion of the surface, retracted at
another, and thus the corpuscle gradually moves or ' flows ' from
place to place, and envelopes or eats up substances, such as grains
of carmine, which come in its way. This kind of motion was first
observed in the amoeba, and is therefore called amoeboid. It is
perhaps due to local alterations of surface tension; at any rate,
similar phenomena can be thus produced artificially. The leuco-
cytes of human blood are not all of the same size, and differ also in
other respects. They may be classified according to the presence
or absence of granules in their protoplasm, and the fineness or
coarseness of the granules ; according to the chemical nature of the
dyes with which the granules most readily stain, and according to
the form of the nucleus. Five or six varieties of leucocytes may
thus be distinguished in normal blood (Frontispiece] :
1. Polymorphonuclear Neutrophile Cells. — The nucleus assumes a
great variety of forms, often contorted or deeply lobed, the lobes being
united by fine strands of chromatin. The cytoplasm contains numerous
fine refractive granules, which stain best neither with simple acid dyes
like eosin nor with simple basic dyes like methylene blue, but with
mixtures which roust be assumed to contain ' neutral ' stains, like
Ehrlich's so-called triacid stain.* These cells make up 65 to 75 per
cent, of the total number of leucocytes. Their diameter is 10 to
12 p.
2. Eosinophile Cells (12 to 15 /x in diameter), much less numerous in
normal blood than the neutrophiles (less than 5 per cent, of the whole),
but found in considerable numbers in the serous cavities, the connec-
tive tissue, and the bone-marrow. The granules in the cytoplasm are
coarser than the neutrophile granules, and stain much more deeply
with eosin. The nucleus may be simple, lobed, or even divided into
fragments between which no connection can be traced. It is less rich
in chromatin, and stains less easily with basic dyes, like methylene blue,
than the nucleus of the first variety.
3. Large Mononuclear (also called Transitional) Leucocytes, with a
diameter of 12 to 15 /*. They possess a large simple or slightly lobed
nucleus, poor in chromatin, surrounded by a relatively great amount
of cytoplasm, with faint neutrophile granules — i.e., granules which stain
with neutral dyes. They constitute 3 to 5 per cent, of the total number
of leucocytes.
4. Lymphocytes of Two Varieties — (a) Small Lymphocytes. — Smaller
cells than any of the preceding (diameter 6 p.), possessing a single large
nucleus, surrounded by a comparatively small amount of non-granular
cytoplasm; 20 to 25 per cent, of the leucocytes of the blood belong to
this group. The lymphocytes are markedly deficient in the power of
amoeboid motion in comparison with the other varieties of colourless
corpuscles.
(b) Large Lymphocytes. — The largest of all the white cells of the blood,
and at least twice as large as the small lymphocytes. They possess
a relatively great proportion of cytoplasm, which is devoid of granules.
They constitute no more than I per cent, of the total number of the
colourless corpuscles.
* A mixture of orange G., acid fuchsin, and methyl green.
2
t8 THE CIRCULATING LIQUIDS Of THE BOb\
5. ' Mast Cells,' or ' Basophiles,' the least numerous variety (o-5 per
cent, of the total number). Very few are to be found in the normal
blood of adults, but more in children. They are somewhat smaller
than the neutrophiles (average diameter about 10 p.). The nucleus is
irregularly trilobed. The protoplasm shows coarse granules, which do
not glitter like the granules of the eosinophile cells, and are therefore
less conspicuous hi the unstained condition. Unlike the eosinophile
granules, they stain with basic dyes, such as methylene blue.
Blood-Plates, or Thrombocytes. — When blood is examined im-
mediately after being shed, small colourless bodies (i to 3 // in
diameter) of various shapes, but usually round or oval, may be seen.
These are the blood-plates or platelets, also called thrombocytes,
on account of their function in the coagulation of blood. If the
blood is not at once subjected to some procedure which prevents
clotting, the platelets swell and then break up. There is reason to
believe that in most of the methods of preventing coagulation the
essential action is to hinder the break-up of the platelets (p. 37).
They can be isolated by receiving a drop of blood from the finger
upon a well-cleaned cover-slip, which is then laid, supported by two
thin glass fibres, on a carefully cleaned slide. The plasma with the
coloured corpuscles and leucocytes are washed away by irrigating
the space between slide and slip with a suitable solution, e.g., a
salt solution containing a certain proportion of manganese sulphate,
which prevents disintegration of the platelets. The platelets stick
to the cover-slip (Deetjen). They can then be fixed and stained.
The blood-plates can even, like leucocytes, be kept alive on
the warm stage in an appropriate medium (agar, to which certain
salts have been added), and then show lively amoeboid movements
(Deetjen). They have been described as nucleated cells, although
the nucleus is not easy to stain, and with the ultra-microscope, a
delicate means of testing whether such an object as a platelet is
optically homogeneous, no evidence of the presence of a nucleus
has been obtained. The origin of the platelets has been a matter of
lively controversy. They are not produced by the breaking up of
other elements of the shed blood, for they have been observed
within the freshly excised, and therefore still living, capillaries —
in the mesentery of the guinea-pig and rat (Osier). According to
the best evidence, they are derivatives neither of the erythro-
cytes nor of the leucocytes of the blood, but are developed from
special elements (so-called megakaryocytes) of the blood-forming
organs (bone-marrow) (J. H. Wright).
Enumeration of the Blood-Corpuscles. — This is done by taking a
measured quantity of blood, diluting it to a known extent with a
liquid which does not destroy the corpuscles, and counting the
number in a given volume of the diluted blood (p. 67) .
The average number of red corpuscles in a cubic millimetre of
blood is about 5,000,000 in a healthy man, and about 4,500,000 in
THE BLOOD-CORPUSCLES
1:4-10
a healthy woman, but a variation of 1,000,000 up or down can hardly
be considered abnormal. In persons suffering from profound anaemia
the number may sink to 1,000,000 per cubic millimetre, or even
less. In one case of pernicious anaemia, only 143,000 corpuscles
per cubic millimetre were present, the
lowest number recorded. In new-born
children the average is over 6,000,000,
and in the inhabitants of high plateaus
or mountains it may rise to 7,000,000 or
Fig. s.-Curveshowingthe Number eyen more. In the latter instance a
of Red Corpuscles at Different residence of a fortnight in the rarefied
Ages (after Sorensen's Estima- a|r js sufficient to bring about the in-
tions). The figures along the , , .j £
horizontal axis are years of age, crease> and a subsequent residence of a
those along the vertical axis fortnight in the lowlands to annul it.*
millions of corpuscles per cubic jn certain pathological conditions a
millimetre of blood. , • • j.« » i« -L £.
great increase in the relative number of
corpuscles (polycythsemia) is found. Over 13,000,000 erythrocytes
to the cubic millimetre have been counted in a case of cyanosis (im-
perfect oxygenation of the blood, with blueness of the lips, etc.), due
to congenital disease of the heart. An interesting form of experi-
mental polycythsemia is caused by injection of adrenalin.
The number of white blood-corpuscles is on the average about
10,000 per cubic millimetre of blood, or
one leucocyte for every 500 red blood-
corpuscles. But if the count is made
when digestion is relatively inactive,
four to five hours after a meal, it gives
no more than 7,000 to the cubic milli-
metre. In new-born children the
average number is over 18,000 per
cubic millimetre. The total leucocyte
count, and still more the so-called dif-
ferential count, i.e., the determination
of the relative number of the different
kinds of leucocytes, is often resorted to
in the study of pathological conditions.
A distinct increase in the number is
designated leucocytosis. In leukaemia
the number of white corpuscles is
enormously increased — on the average
to about 300,000, but in extreme cases
to 600,000 per cubic millimetre — while at the same time the number
* In 113 apparently healthy students (male) the average number of red
corpuscles was 5,190,000 per cubic millimetre. In 104 of these, the number
ranged from 4,000,000 to 6,400,000; in 71 (or 63 per cent, of the whole), from
4,400,000 to 5,500,000; in 3, from 3,500,000 to 3,900,000; in 5, from 6,500,000
to 7,000,000. In one observation the number reached 7,300,000.
m
Fig. 4. — Curve showing Propor-
tion of White Corpuscles to Red
at Different Times of the Day
(after the Results of Hirt). At
I the morning meal was taken ;
at II the midday meal; at III
the evening meal. During
active digestion the number of
lymphocytes in the blood is
greatly increased, both abso-
lutely and relatively to the
number of the other leucocytes.
40 THE CIRCULATING LIQUIDS OF THE BODY
of the red corpuscles is diminished; and the ratio of white to red
may approach 1:4. As the anaemia rapidly advances towards the
fatal termination of an acute case, and the erythrocyte count falls to
1,000,000, or even less, the ratio may come still nearer to unity. An
increase in the number of leucocytes has also been observed in cer-
tain infective diseases as part of the inflammatory reaction. There
are also physiological variations, even within short periods of time ;
for example, the number of lymphocytes is increased when digestion
is going on (digestive lymphocytosis) . The normal number of
blood-plates varies from a quarter to half a million to the cubic
millimetre, but may be greater in disease and at high levels
(Kemp).
Life-History of the Corpuscles. — The corpuscles of the blood, like
the body itself , fulfil the allotted round of life, and then die. They
arise, perform their functions for a time, and disappear. But
although the place and mode of their origin, the seat of their destruc-
tion or decay, and the average length of their life, have been the
subject of active research and still more active discussion for many
years, much yet remains unsettled.
Origin of the Erythrocytes. — In the embryo the red corpuscles, even
of those forms (mammals) which have non-nucleated corpuscles in
adult life, are at first possessed of nuclei, and approximately spherical
in form. In the human foetus, at the fourth week all the red corpuscles
are nucleated. Later on the nucleated corpuscles gradually diminish
in number, and at birth they have almost or altogether disappeared,
some of them, at least, having been converted by a shrivelling of the
nucleus into the ordinary non-nucleated form. In the newly born rat,
which comes into the world in a comparatively immature state, many
of the red corpuscles may be seen to be still nucleated. The first cor-
puscles formed in embryonic life are developed outside of the embryo
altogether. Even before the heart has as yet begun to beat, certain
cells of the mesoderm (see Chapter XIX.) in a zone (' vascular area ')
around the growing embryo begin to sprout into long, anastomosing
processes, which afterwards become hollowed out to form capillary
bloodvessels. At the same time clumps of nuclei, formed by division
of the original nuclei of the cells, gather at the nodes of the network.
Around each nucleus clings a little lump of protoplasm, which soon
develops haemoglobin in its substance; and the new-made corpuscles
float away within the new-made vessels, where they rapidly multiply
by mitosis. In later embryonic life the nucleated corpuscles continue
in part to be developed within the bloodvessels in the liver, allantois,
spleen, and red bone-marrow, and in certain localities in the connective
tissue, by mitotic division of previously existing nucleated corpuscles,
in part to be formed endogenously within special cells in the liver and
perhaps other organs. Still later the nucleated corpuscles give place in
the blood of the mammal to non-nucleated erythrocytes. Many of
these are doubtless derived from the nucleated corpuscles, but some
appear to be produced in the interior of certain cells of the connective
tissue, and are non-nucleated from the start.
In the mammal in extra-uterine life the chief seat of formation
of the red blood-corpuscles, or haematopoiesis, is the red marrow of
THE BLOOD-CORPUSCLES
21
the bones of the skull and trunk, and of the ends of the long bones
of the limbs. Special nucleated cells in the marrow, originally
colourless, multiply by karyokinesis, take up haemoglobin or, what
is much more likely, form it within their protoplasm, and are
transformed by various stages into the ordinary non-nucleated red
corpuscles, which then pass into the blood-stream. These blood-
forming cells have received the name of erythroblasts or haemato-
blasts. According to their size, erythroblasts have been distinguished
as normoblasts, megaloblasts, and microblasts. The normo-
blasts are most numerous, and have about the same diameter as
the full-formed erythrocytes, into which they are believed to
develop. The megaloblasts are larger, and the microblasts smaller,
and they are thought to be the precursors of those aberrant forms
of erythrocytes sometimes found in the blood in certain diseases.
After haemorrhage rapid regeneration of the blood takes place, so
that in a few weeks the loss of even as much as a third of the total
blood is made good. The plasma is much sooner restored to its
normal amount than the corpuscles. Microscopical examination
shows in the red marrow the tokens of increased production of
coloured corpuscles, and nucleated erythrocytes appear in the
blood, the normoblasts being, as it were, hurried into the circula-
tion before the transformation which normally results in the dis-
appearance of the nucleus is complete. The same is true in
severe pathological anaemias, e.g., pernicious anaemia. It is a
matter of interest that other organs also, which in embryonic
life perform a haematopoietic function, particularly the spleen,
may, in such emergencies, again take on the office of forming
blood-corpuscles.
A constant destruction of red blood- corpuscles must go on, for
the bile-pigment and the pigments of the urine are derived from
blood-pigment. The bile-pigment is formed in the liver. It con-
tains no iron ; but the liver cells are rich in iron, and on treatment
with hydrochloric acid and potassium ferrocyanide, a section of
liver is coloured by Prussian blue. Iron must therefore be
removed by the liver from the blood-pigment or from one of its
derivatives; and there is other evidence that the liver is either one
of the places in which red corpuscles are actually destroyed, or
receives blood charged with the products of their destruction.
Although it cannot be doubted that in all animals whose blood
contains haemoglobin the iron found in the liver bears an important
relation to the building up or breaking down of the blood-pigment,
the injection of haemoglobin or haemin, indeed, increasing markedly
the amount of iron in the liver, as well as in the spleen, bone-marrow
and other tissues, this does not seem to be the only function of the
hepatic iron, for the liver of the crayfish and the lobster, which
have no haemoglobin in their blood, is rich in iron. Destruction of
22 THE CIRCULATING LIQUIDS OF THE BODY
erythrocytes may also take place in the spleen and bone-marrow.
Although the statement that free blood-pigment exists in demon-
strable amount in the plasma of the splenic vein is incorrect, red
corpuscles have been seen in various stages of decomposition within
large amoeboid cells in the splenic pulp; and deposits containing
iron have been found there and in the red bone-marrow in certain
pathological conditions. But there is no good foundation for the
statement sometimes rather fancifully made that the spleen is in
any special sense the ' graveyard of the red corpuscles.' Some of
the coloured corpuscles may break up in the blood itself, forming
granules of pigment, which may then be taken up by the liver, spleen,
and lymph glands. Indeed, it is probable that a large proportion
of the worn-out erythrocytes are finally destroyed in the blood-
stream. The portal circulation may be more than other vascular
tracts a seat of this natural decay, perhaps in virtue of the presence
of substances with a hsemolytic action (p. 28) absorbed from the
alimentary canal.
It has been argued that the erythrocytes must be short-lived,
since they are devoid of nuclei (p. 6), and attempts have been
made to calculate the average time for which they survive in the
circulation from the amount of haemoglobin (or of its derivative,
haematin) required to furnish the daily excretion of bile-pigment.
The results arrived at, however, are not sufficiently trustworthy to
warrant their citation.
Origin and Fate of the Leucocytes. — There has been much dis-
cussion as to the origin of the white blood-corpuscles. The
numerous theories fall into two groups, which have been designated
somewhat pompously the monistic and the dualistic. According
to the first, all the colourless corpuscles arise from a single type
of parent cell, namely, the lymphocyte type, in its small or large
variety. According to the dualistic school, a fundamental distinc-
tion exists between the lymphocytes, or cells peculiar to lymphoid
tissues, and to the blood on the one hand, and the remaining varieties
of leucocytes on the other. The former are supposed to be derived
from the lymphoblasts of lymphoid tissue, and the latter from the
myeloblasts, the forerunners of the myelocytes of bone-marrow.
The question has recently been studied by Foot by a new method,
namely, by cultivating chicken marrow outside of the body, and
watching the transformation of certain of its cells. He concludes
in favour of the development of the polymorphonuclear leucocyte
from a lymphoid type of cell existing in the marrow, a conclusion
in harmony with the monistic view. As regards their immediate
source, the small lymphocytes of the blood are undoubtedly derived
from the lymph, and are identical with the lymph-corpuscles.
That they are formed largely in the lymphatic glands is shown
by the fact that the lymph coming to the glands is much poorer
THE BLOOD-CORPUSCLES 23
in corpuscles than that which leaves them. The lymphatic glands,
however, although the principal, are not the only seat of formation
of lymphocytes, for lymph contains some corpuscles before it has
passed through any gland ; and although a certain number of these
may have found their way by diapedesis from the blood, others are
developed in the diffuse adenoid tissue, or in special collections of it,
such as the thymus, the tonsils, the Peyer's patches and solitary
follicles of the intestine, and the splenic corpuscles. To a very
small extent white blood-corpuscles may multiply by karyokinesis
or indirect division in the blood.
The fate of the leucocytes is even less known than that of the
red corpuscles, for they contain no characteristic substance, like
the blood-pigment, by which their destruction may be traced. That
they are constantly disappearing is certain, for they are constantly
being produced. Not a few of them actually escape from the
mucous membranes of the respiratory, digestive, and urinary
tracts. The remnants of broken-down leucocytes have been found
in the spleen and lymph glands. It must be assumed that many
break up in the blood-plasma itself.
SECTION II. — GENERAL PHYSICAL AND CHEMICAL PROPERTIES OF
THE BLOOD.
Fresh blood varies in colour, from scarlet in the arteries to
purple-red in the veins. It is a somewhat viscid liquid, with a
saline taste and a peculiar odour.
Viscosity of Blood. — The viscosity of normal dog's blood is about
six times greater than that of distilled water at body temperature.
It can be determined by allowing the blood to flow through a capil-
lary tube of known dimensions under a definite pressure, and
measuring the amount which escapes in a given time. In general
the viscosity and specific gravity of the blood vary in the same
direction, although there is not an exact proportionality between
them. Thus, sweating, which causes a diminution of the water of
the blood, causes also an increase in its viscosity. With increasing
temperature the viscosity of the blood diminishes, as is the case
with other liquids (Burton-Opitz).
In polycythsemia, where the number of erythrocytes in propor-
tion to plasma is greatly increased, the viscosity of the blood in-
creases in an equal degree. In one case of polycythsemia, with a
blood-count of 8,300,000, the viscosity was 9-4 times that of water;
in a case of marked chlorosis it was only 2-14. But the importance
of this factor in causing an abnormal blood-pressure by increasing
or diminishing the resistance to the blood-flow has been exaggerated.
Although it has been shown that in the living vessels, so long as
24 THE CIRCULATING LIQUIDS OF THE BODY
their calibre remains constant, the flow is affected by changes in
the viscosity of the blood, just as in glass tubes, compensation by
adjustment of the vascular calibre is so ample and so easy thai
even the greatest alterations of viscosity produce little effect on
the mean blood-pressure.
Reaction of Blood. — In the sense in which the term is used in
physical chemistry, the reaction of a solution depends on the pro-
portion between its content of hydrogen (H + ) and hydroxyl
(OH — ) ions, an excess of hydrogen ions corresponding to an acid
and an excess of hydroxyl ions to an alkaline reaction. It has been
shown by a physical method (the determination of the electro-
motive force of a cell containing blood or serum as one liquid) that
hydroxyl ions are present only in small excess, and that blood is
really but a little more alkaline than distilled water. Practically,
it may be regarded as a neutral liquid. Under a great variety of
conditions, physiological and pathological, its reaction remains
almost unchanged. Yet it is known that acids (carbon dioxide,
lactic, phosphoric, and sulphuric acids) are constantly being pro-
duced in the normal metabolism of the tissues. The administra-
tion of large quantities of acid or alkali causes a surprisingly small
effect. In diabetes, even when it can be proved that an abnormal
production of acid substances is taking place, the blood shows little,
if any, diminution in the proportion of hydroxyl ions; it remains
to all intents and purposes a neutral liquid. In diabetic coma,
where the blood may in extreme cases turn blue litmus red, the
true reaction is only slightly altered.
The manner in which the reaction of the blood, the tissue liquids,
and probably the protoplasm itself, is regulated within such narrow
limits is a subject of great interest. For there is reason to believe
that it is of the utmost moment that the equilibrium should be
maintained not only in order that the functions of the tissues may
be properly performed, but that danger to life may be averted.
To be sure, the excretory organs, the lungs and the kidneys, provide
the means by which the excess of acid (or of alkali) is finally, under
normal circumstances, eliminated. Other regulative mechanisms
also exist. For example, it has been shown that when an excessive
production of acids (acidosis) occurs in conditions of disordered
metabolism, or when acids are purposely administered in large
amount, a greater quantity of ammonia, split off from the pro-
teins, is mobilized to aid in neutralizing the acids. But very
simple experiments on blood in vitro are sufficient to show that
the blood itself has a great capacity, as compared with water, to
resist a change in its reaction even when large amounts of acid or
alkali are added to it. The secret of the reaction-regulating power
lies, therefore, to a large extent in the blood itself. Two factors
have been shown to be of importance: (i) The power of the proteins,
GENERAL PHYSICAL AND CHEMICAL PROPERTIES 25
in virtue of their amphoteric character, to combine either with
acids or with bases, so that, when excess of base is added to blood,
the proteins act as acids, and neutralize the base; when excess of
acid is added, the proteins act as bases, and neutralize the acid.
(2) The equilibrium of certain of the inorganic constituents of the
blood (carbon dioxide, the carbonates, and the phosphates) is such
that even great variations in the concentration of any of these,
such as may normally occur, produce scarcely any effect upon the
concentrations of the hydrogen and hydroxyl ions.
Thus, when phosphoric acid and sodium hydroxide are added to
water in certain proportions, and the solution placed under a certain
tension of carbon dioxide (which is kept constant), we get a more or
less accurate imitation of blood as regards the inorganic substances
concerned in the regulation of its reaction, sodium bicarbonate
(NaHCO3) and disodium phosphate (NagHPC^) being present in the
solution as in blood. It is found that when the quantities are so chosen
that the H + concentration lies within the limits of variation of the
normal blood reaction, relatively large quantities of alkalies can be
added or withdrawn without causing much change in the H + concen-
tration. It can be shown both theoretically and experimentally that
precisely those weak acids present in blood (CO2, NaH2PO4) require the
largest addition of alkali to alter the reaction to a given extent, and
are therefore particularly suited to give stability to the reaction.
Thus carbon dioxide requires twenty-four times, and monosodium
phosphate thirty-three times, as much alkali as an equivalent solution
of acetic acid to cause a given alteration of colour in rosolic acid
(E. Henderson).
The so-called ' titratable ' alkalinity of blood or serum, measured by
the amount of standard acid which must be added before the colour of
the indicator used changes from alkaline to acid, bears no necessary or
fixed proportion to the actual alkalinity. When blood, for instance,
is titrated with hydrochloric acid, with methyl orange as indicator, at
the point where the red colour appears all the disodium phosphate and
sodium bicarbonate will have been changed into monosodium phos-
phate and carbon dioxide, all the alkali removed from combination
with proteins, a certain amount of acid -protein compounds formed,
and other minor reactions produced (Henderson). It is difficult to
correlate the quantity deduced from such a titration with any physio-
logical condition, although undoubtedly it bears some relation to the
acid-neutralizing power of the blood, and some relation to its real
reaction. Still, by titration information of value can be obtained
which is not yielded by the physico-chemical method in regard to the
potential ' acid capacity ' of the blood and its power of resistance against
acid-poisoning.
What is estimated here is the quantity of acid required to satisfy the
proteins and to react with the carbonates and phosphates before that
concentration of hydrogen and hydroxyl ions just necessary to cause
the change of colour is established. This is not the same for different
indicators, since there is a certain minimum ratio in the concentration
of these ions at which each indicator turns in one or the other direction,
none turning precisely at the neutral point. Thus serum appears to be
acid when tested with phenolphthalein, and alkali must be added to
the serum before the pink colour indicating alkalinity is produced.
On the other hand, with litmus or methyl orange it gives the alkaline
26 THE CIRCULATING LIQUIDS OF THE BODY
reaction, and a considerable amount of acid must be added before the
colour of the indicator which denotes acidity appears. The true re-
action of the serum is not, of course, at one and the same time both
alkaline and acid; but it is so near neutrality that it falls just below the
degree of alkalinity necessary to give the pink colour with phenol-
phthalein, and just below the degree of acidity which gives the pink
colour corresponding to an acid reaction with methyl orange. Certain
indicators — for example, rosolic acid — turn so as to give sharp colour
reactions at about the concentration of hydrogen and hydroxyl ions
in the blood, and these may possibly be of use in determining the
changes in the true reaction for clinical purposes (Adler) .
More closely related to the true alkalinity of the blood than the
titratable alkalinity is the carbon dioxide content. The estimation
of the total carbon dioxide in a sample of blood throws light upon
the capacity of the blood to perform one of its most important
functions — the transportation of carbon dioxide — and to preserve
one of its essential properties — an almost neutral reaction — in the
presence of an excessive intake or production of acid substances.
In herbivorous animals the carbon dioxide content of the blood is
easily lessened by the administration of acids, but in carnivora
and in man it is much more difficult to bring about such a decided
effect, for the reason already mentioned, the acid being neutralized
by ammonia. In many diseases, however, and particularly in those
accompanied by fever, this protective mechanism breaks down.
Specific Gravity of Blood. — The average specific gravity of blood
is about 1066 at birth. It falls during infancy to about 1050 in
the third year, then rises till puberty is reached to about 1058 in
males (at the seventeenth year), and 1055 in females (at the four-
teenth year). It remains at this level during middle life in males,
but falls somewhat in females. In chlorotic anaemia of young
women it may be as low as 1030 or 1035. It rises in starvation.
Sleep and regular exercise increase it (Lloyd Jones).* The specific
gravity of the serum or plasma varies from 1026 to 1032.
The Electrical Conductivity of Blood.— The liquid portion of the
blood conducts the current entirely by means of the electrolytes
dissolved in it, the most important of these being the inorganic
salts; and the conductivity of the serum varies, in different speci-
mens of blood, within a comparatively narrow range. The con-
ductivity of entire (defibrinated) blood, on the contrary, varies
within wide limits. For instance, in a case of pernicious anaemia
the conductivity of the blood was found to be almost double that
of normal human blood, while the conductivity of the serum was
normal. The most influential factor which governs this variation
* In 165 students (male) the average specific gravity of the blood, as deter-
mined by Hammerschlag's method (p. 62) was 1054-4. In 149 of these the
variation was from 1050 to 1065; in 94 (or 57 per cent, of the whole), from
1054 to 1060; in 4, from 1046 to 1049; in 9, from 1066 to 1070. In 3 the
specific gravity was only 1040 to 1042.
GENERAL PHYSICAL AND CHEMICAL PROPERTIES 27
is the relative volume of the corpuscles and serum. When the
blood is relatively rich in corpuscles and poor in serum, its con-
ductivity is low; when it is poor in corpuscles and rich in serum,
its conductivity is high. The explanation is that the corpuscle
refuses passage to the ions of the dissociated molecules, which, in
virtue of their electrical charges, render a liquid like blood a con-
ductor (p. 428), or permits them only to pass very slowly, so that
the intact red corpuscles have an electrical conductivity so many
times less than that of serum, that they may, in comparison, be
looked upon as non-conductors (Practical Exercises, p. 69).
The Relative Volume of Corpuscles and Plasma in Unclotted
Blood, or, what can be converted' into this by a small correction,
the relative volume of corpuscles and serum in defibrinated blood,
can be easily determined, with approximate accuracy, by com-
paring the electrical conductivity of entire blood with that of its
serum.* Another method, more suitable for clinical work, though
not so accurate, is the so-called hgematocrite method. A small
quantity of blood is centrifugalized in a graduated glass tube of
narrow bore until the corpuscles have been collected into a solid
' thread ' at the outer extremity of the tube. Their volume and
that of the clear plasma which has been separated from them are
then read off on the scale. The hsematocrite must rotate at such a
high speed (10,000 turns a minute) that separation of the corpuscles
from the plasma is accomplished before clotting has occurred.
Dilution of the blood with liquids which prevent clotting is not
permissible for exact work (Practical Exercises, p. 68). By these
and other methods too elaborate for description here, it has been
shown that the plasma or serum usually makes up rather less than
two-thirds, and the corpuscles rather more than one-third, of the
blood. But this proportion is, of course, liable to the same varia-
tions as the number of corpuscles in a cubic millimetre of blood.
It depends, further, the number of corpuscles being given, on the
average volume of each corpuscle. For instance, when the mole-
cular concentration, and therefore the osmotic pressure (p. 427),
of the plasma is reduced, as by the addition of water or the abstrac-
tion of salts, water passes into the corpuscles and they swell; when
the molecular concentration of the plasma is increased, by the
abstraction of water or the addition of salts, water passes out of
the corpuscles, and they shrink. In human serum the average
* The formula p *» «rr (174 - K(b)), where p is the number of c.c. of serum
in 100 c.c. of blood; K(b], K(s), the specific conductivities respectively of the
blood and serum (both measured at or reduced to 5° C., and, to obtain whole
numbers, multiplied by io4), may be used in the calculation. K is the specific
conductivity of the liquid — i.e., the conductivity of a cube of the liquid of
i centimetre side. The conductivity 01 a similar cube of mercury is 10,630.
28 THE CIRCULATING LIQUIDS OF THE BODY
depression of the freezing-point below that of distilled water, which
is a measure of the molecular concentration and of the osmotic
pressure, is about 0-56° C. (Practical Exercises, p. 73). For clinical
purposes, the determination of the relative volume of corpuscles and
plasma is most useful in cases where the average size of the erythro-
cytes departs from the normal, and where, accordingly, the enumera-
tion of the corpuscles would give an erroneous idea of their total mass.
Laking of Blood, or Haemolysis. — Even in thin layers blood is
opaque, owing to reflection of the light by the red corpuscles. It
becomes transparent or ' laky ' when by any means the pigment
is brought out of the corpuscles and goes into true solution. Re-
peated freezing and thawing of the blood, the addition of water,
the passage of electrical currents, constant and induced,* putre-
faction, heating the blood to 60° C., and many chemical agents (as
bile-salts, ether, saponin), cause this change. Certain complex
poisons of animal origin, such as snake-venoms, bee-poison, spider-
poison or arachnolysin, and certain toxins produced by pathogenic
bacteria — for instance, tetanolysin, formed by the tetanus bacillus
— also possess decided haemolytic power. The blood-serum of
certain animals acts on the coloured corpuscles of others, and sets
free their pigment — for example, the serum of the dog or ox causes
haemolysis of rabbit's corpuscles; the serum of the ox, goat, dog,
or rabbit lakes guinea-pig's corpuscles. But rabbit's serum does
not lake dog's corpuscles, and guinea-pig's serum is inactive towards
the corpuscles both of the rabbit and the dog. It has been shown
that in hsemolysis by foreign serum two bodies are concerned: one,
which is easily destroyed by heating to about 56° C., the so-called
complement, and another, the intermediary body or amboceptor,
which is not affected by being heated to this temperature. Thus
if dog's serum be heated to 56° C. for twenty minutes, no amount
of it will lake rabbit's washed corpuscles — that is, rabbit's corpuscles
freed from their own serum by repeated washing with salt solution
and centrifugalization. If, however, serum which is not itself
hsemolytic for rabbit's blood (e.g., rabbit's or guinea-pig's serum)
be added to the washed rabbit's corpuscles, they will be laked by
the heated dog's serum. Unheated dog's serum will lake rabbit's
corpuscles, whether they have been washed free from their own
serum or not (Practical Exercises, p. 71).
The hypothesis which best explains these facts and many similar
ones is that dog's serum contains both of the bodies necessary for
haemolysis of rabbit's corpuscles. When the complement has been
rendered inactive by heating, the amboceptor cannot cause laking
* The laking action of induced currents is due simply to the heating of the
blood. Condenser discharges, which cause liberation of the haemoglobin
without raising the temperature of the blood as a whole to the point at which
heat-laking occurs, possibly act in the same way by causing local heating of
the corpuscles owing to their high resistance.
GENERAL PHYSICAL AND CHEMICAL PROPERTIES 29
by itself. Rabbit's serum contains complement, but not the
specific amboceptor necessary for the laking of rabbit's corpuscles.
Accordingly, the addition of fresh rabbit's serum to heated dog's
serum restores complement to the latter, and thus it is again ren-
dered active for rabbit's corpuscles. The amboceptor is supposed
to unite on the one hand with certain groups in the corpuscle and
on the other with the complement, which is thus enabled to develop
its hsemolytic action upon the envelope or the stroma. The com-
plement is incapable of acting, even in the presence of amboceptor,
if the temperature is reduced to o° C. Nevertheless, the corpuscles
take up amboceptor at this temperature, and on this fact is based
a method of freeing serum from amboceptor. For example, if
dog's serum and excess of rabbit's washed corpuscles, both pre-
viously cooled to o° C., be mixed and placed at o° C. for some hours,
and the serum then removed, it will be found that it has lost the
power of laking rabbit's corpuscles, washed or unwashed, at air or
body temperature, although it will still do so on the addition of
dog's serum in which the complement has been destroyed by
heating it to 56° C. The real nature and mode of action of com-
plements and amboceptors are not yet satisfactorily determined.
The laws of chemical equivalents and definite proportions do not
seem to be observed in the reactions into which they enter. It has
therefore been suspected that the bodies in question belong to the
group of ferments, or are closely related thereto, and there is some
evidence that a fat-splitting enzyme, or lipase, is concerned in the
complement action (Jobling).
As to the manner in which haeraolytic agents cause the liberation of
the blood-pigment, the fact that in so many forms of laking the cor-
puscles swell up before the haemoglobin escapes indicates that the
entrance of water is an important step. The entrance of water is
favoured by changes produced in the chemical and physical condition
of certain constituents of the superficial layer (envelope) of the cor-
puscle, as well as by changes in its interior. Saponin and ether, for
example, are known to be solvents of cholesterin and lecithin, and
cholesterin and lecithin are important constituents of the stroma and
envelope of the erythrocyte. It is easy to understand that if a portion
of one or both of these substances is dissolved, or altered without being
actually dissolved, profound changes may be produced in the permea-
bility of the corpuscle to water and to the salts dissolved in the liquid
in which the erythrocytes are suspended. In addition to this change
of permeability, many laking agents, perhaps all, exert also a more direct
influence on the normal relations of the native blood-pigment to the
stroma. Ether and saponin, for instance, seem to act in two ways —
by disorganizing the envelope through solution of its lipoids, and thus
increasing its permeability to water; and by helping to dissociate the
blood-pigment-stroma complex by exerting a pull on the lipoids of the
stroma, while the water simultaneously exerts a pull on the pigment.
The conclusion follows from this view of haemolysis, that the erythro-
cytes, normally so perfectly adapted to the plasma in which they float,
may, when the conditions on which th'eir equilibrium with it depends
30 THE CIRCULATING LIQUIDS OF THE BODY
are altered, be rapidly and inevitably destroyed by that very plasma
itself. It is, indeed, the very fact of the exquisite adaptation of liquid
and cell for a strictly regulated exchange of material which constitutes
the danger when the regulation is upset. A liquid like mercury, which
is not adapted either to give anything to erythrocytes in contact with
it or to take anything from them, would not cause haemolysis, even if
the permeability of the corpuscles for water or sodium chloride were
increased to any extent. The continued survival of the erythrocytes in
an aqueous solution of salts and proteins like the plasma — nay, more,
the protection of the corpuscles up to a certain point by the plasma
against the attack of extraneous haemolytic agents — are facts we are
prone to take so much for granted as to forget that they depend entirely
upon a most delicate adjustment of the permeability of the corpuscles
for essential constituents of the plasma. Disturb these relations to a
sufficient degree, and the plasma becomes a poison to the erythrocytes
not much less deadly than distilled water.
When we add to blood a haemolytic substance, and see that presently
the blood-pigment has left the corpuscles, we are apt to attribute the
whole effect to the foreign material added, and to say that the saponin,
the ether, the alien serum, has laked the blood. In a certain sense this
is true, but it is not the whole truth. In reality the haemolytic agent
has acted in an essential degree, although nob exclusively, by overthrow-
ing the equilibrium between the corpuscles and the aqueous solution
of certain substances in which they are suspended. To say that the
foreign substance alone causes the haemolysis is no more accurate than
it would be to say that a man swimming strongly in a rough sea, who
sinks when hit and stunned by a piece of wreckage, was drowned by
the blow, and not by the sea. No doubt it is true that, but for the
blow, he would have continued to swim ; yet, in reality, he loses his life
because he is environed by a medium deadly to him as soon as his power
of adjustment to it has been too much diminished. On land, the blow
would have stunned, but would not have killed him. In like manner,
to glance at one phase of the natural decay of the corpuscles within the
body, an erythrocyte may float secure in its watery environment
through many rounds of the circulation. But its security is not static,
like that of a log floating on the water. It is dynamic, a triumph of
perfect physico-chemical poise, as the security of the swimmer, still
more of the tight-rope dancer, is dynamic, a triumph of perfect neuro-
muscular poise. The time, however, arrives when, either through
changes in the corpuscle itself (the changes of cellular senility, as we
may call them), or through changes in the environing medium, or
through a combination of the two, the adjustment is upset, and the
erythrocyte is now destroyed by the plasma in which it has so long
lived.
In general haemolysis by foreign serum is preceded by agglutina-
tion or aggregation of the corpuscles into groups. Agglutination
may be obtained without haemolysis by heating the haemolytic
serum to the temperature at which the complement is destroyed,
since the agglutinating agents, or agglutinins, are relatively resistant
to heat. Besides the amboceptors naturally present in the blood
of certain animals, and capable, in conjunction with complement, of
haemolyzing the corpuscles of certain other animals, amboceptors
may be produced in much greater strength by artificial means.
GENERAL PHyslCAL AMD CHEMICAL PROPERTIES 31
When the corpuscles of one animal are injected intraperitoneally
or subcutaneously into an animal of a different kind, the serum of
the latter acquires the property of agglutinating and laking the
corpuscles of an animal of the same kind as that whose corpuscles
have been injected. This is especially marked if the injection is
several times repeated at intervals of a few days. If, for instance,
dog's corpuscles are injected into a rabbit, the rabbit's serum after
a time becomes strongly hsemolytic for dog's corpuscles. It also
agglutinates them. This is due to the appearance in the rabbit's
serum of an amboceptor and an agglutinin which have a specific
action on dog's corpuscles. Such a serum is often termed an
immune serum, and the animal which has received the injections
is spoken of as immunized in regard to this particular kind of
corpuscles. For the reaction involved in the production of the
amboceptor and agglutinin is a particular case of the peculiar and
specific response which the body makes to the presence of foreign
juices or cells, including bacteria, and which constitutes an attempt
to render itself ' immune ' to them.
Many other animal cells besides the coloured blood-corpuscles give
rise, when injected, to similar specific substances (cytolysins), which
cause destruction of cells of the same kind— e.g., leucocytes and
spermatozoa.* The process of haemolysis is more easily followed
than the cytolysis of ordinary cells. Yet in its main features it is
essentially similar.
In each case the specific antibody seems to be produced in response
to the presence of some particular constituent of the foreign cell. The
substances which on injection give rise to antibodies are spoken of as
antigens. In the case of the erythrocytes there is evidence that the
antigens (both the haemolysinogen, which causes the production of
specific amboceptor, and the agglutininogen, the substance which gives
rise to specific agglutinin) are lipoids, or are so closely associated with
the lipoids of the corpuscles that they are extracted by the same solvents.
Thus ethereal extracts of erythrocytes cause the production of haemol-
ysin and agglutinin, just as the entire corpuscles do. The group of
antibodies known as precipitins is of special interest.
Precipitins. — When the serum of one animal is injected into
another of a different group, the serum of the latter acquires the
property of causing a precipitate in the normal serum of animals
of the same group as that whose serum was injected, but not
* Recent studies have tended to modify the view that the cytotoxins
formed after the introduction of different foreign tissues into animals are
quite specific for each tissue. Thus Lambert, using tissues cultivated on
media outside of the body for testing the toxic action, finds that the plasma
of guinea-pigs which have received injections of either chick embryo heart or
intestine becomes toxic for both of these tissues. In like manner the plasma
of guinea-pigs treated by injection of rat sarcoma, a tumour which can be
propagated by inoculation in rats, acquires a toxic action on cultures of both
rat sarcoma and the skin of embryo rats. And the plasma of guinea-pigs
treated with rat embryo skin is also toxic for cells of both types.
32 THE CIRCULATING LIQUIDS OF THE BODY
in the serum of any other kind -of animal. Thus, if human blood
or serum is repeatedly injected at short intervals into a rabbit, the
serum of the rabbit will cause a precipitate in diluted human blood
or serum, but not in the blood or serum of other, animals, except
that of monkeys, where a slight reaction may be obtained. The
specific bodies which cause the precipitation are termed precipitins.
The phenomenon has been made the basis of a method of dis-
tinguishing human blood for forensic purposes. Other animal
fluids and solutions containing tissue proteins likewise give rise to
the production of precipitins. Thus, when cow's milk is injected
into a rabbit, the rabbit's serum acquires the power of precipitating
the caseinogen of cow's milk. Indeed, the response of the animal
body to the presence of foreign proteins is so catholic, and at the
same time so approximately specific, that many artificially isolated
proteins, even those of vegetable origin, after as careful purifica-
tion as possible, occasion, when injected, the production of anti-
bodies which will precipitate from a solution only the variety of
protein injected, or sometimes also, though in slighter degree, pro-
teins nearly related to it.
Anaphylaxis. — Under certain conditions the injection of a toxin, a
serum, or a protein solution, instead of eliciting an immunity reaction
which tends to combat the effects of a subsequent injection of the same
material, produces the opposite result — namely, a sensitization of the
animal which renders the second dose far more harmful than the first.
Thus, Richet found that animals into which eel serum, or the poison
contained in the tentacles of Actinaria, was subcutaneously introduced
became much more sensitive to the toxic action of a second injection.
This phenomenon he designated anaphylaxis, as being the opposite of
the prophylaxis or protection afforded by previous treatment with the
toxins hitherto studied. Later on it was discovered that the sub-
cutaneous injection of a great variety of proteins alien to the animal
into which they are introduced causes anaphylaxis. Only very minute
amounts are necessary for the first or sensitizing dose, and an interval
considerably greater than that employed in the production of an
immune serum (p. 31) is allowed to elapse before the second injection
is made. The symptoms induced in the sensitized animal by a subse-
quent dose of the same material used in sensitization differ somewhat
in different animals, but may be designated in general terms as those
of collapse or shock (anaphylactic shock). They have been especially
studied in the rabbit and guinea-pig, the heart being particularly affected
in the former, and the lungs in the latter. The symptoms are very
severe, and manifest themselves within a very short time (a few minutes)
of the injection. A large proportion of the animals die. If an animal
recovers, it does so suddenly, and for some time afterwards it is in-
sensitive to the particular protein. While the real nature of protein
sensitization or anaphylaxis is not as yet understood, it affords a new
and delicate test for the detection and discrimination of proteins, and
has already been utilized in a number of practical applications. For
instance, the sophistication of sausages with other than the orthodox
ingredients — e.g., with horseflesh — can be thus exposed, since an animal
sensitized by horseflesh will exhibit anaphylaxis to horseflesh, but not
to beef or pork. In like manner, the anaphylactic reaction may be
GENERAL PHYSICAL AND CHEMICAL PROPERTIES 33
used for the identification of human blood. It is probable that an-
aphylaxis plays an important role in certain pathological reactions. It
is well known, for example, that some persons are so susceptible to
particular foods .that the slightest indulgence in them brings on an
attack of urticaria or nettlerash. It has been suggested that these
persons have become sensitized to certain foreign proteins — such as
those existing in eggs, veal, pork, strawberries, shellfish, or whatever
the peccant article of diet may be — possibly by absorption at some
previous time, owing to gastro-intestinal disturbance, of small quan-
tities of the proteins which, have escaped complete digestion.
It is only when proteins are introduced parenterally (i.e., by some
other route than the alimentary canal, such as the subcutaneous tissue,
the blood, or the serous cavities) that the immunity reactions already
described and the phenomenon of anaphylaxis can be experimentally
produced. For in digestion the protein molecule is decomposed, and
although, as will be seen later on, the decomposition products are not
the same for each kind of protein, the factor on which the specificity
of the molecule depends does not survive the hydrolysis.
COAGULATION OF THE BLOOD.
Since changes begin in the blood as soon as it is shed, having
for their outcome clotting or coagulation, we have to gather from
the composition of the stable factors of clotted blood, or of blood
which has been artificially prevented from clotting, some notion of
the composition of the unaltered fluid as it circulates within the
vessels. The first step, therefore, in the study of the chemistry
of blood is the study of coagulation.
When blood is shed, its viscidity soon begins to increase, and
after an interval, varying with the kind of blood, the temperature
of the air, and other conditions, but in man seldom exceeding ten,
or falling below three, minutes, it sets into a firm jelly. This jelly
gradually shrinks and squeezes out a straw-coloured liquid, the
serum. Under the microscope the serum is seen to contain few or
no red corpuscles; these are nearly all in the clot, entangled in the
meshes of a kind of network of fine fibrils composed of fibrin. In
uncoagulated blood no such fibrils are present ; they have accordingly
been formed by a change in some constituent or constituents of
the normal blood. Now, it has been shown that there exists in the
plasma — the liquid portion of unclotted blood — a. substance from
which fibrin can be derived, while no such substance is present in
the corpuscles. In various ways coagulation can be prevented or
delayed, and the plasma separated from the corpuscles. For
example, the blood of the horse clots very slowly, and a low tem-
perature lessens the rapidity of coagulation of every kind of blood.
If horse's blood is run into a vessel surrounded by ice and allowed
to stand, the corpuscles, being of greater specific gravity than the
plasma, gradually sink to the bottom, and the clear straw-yellow
plasma can be pipetted off. Or the addition of neutral salts to
3
34 THE CIRCULATING LIQUIDS OF THE BODY
blood may be used to delay coagulation, the blood being run direct
from the animal into, say, a third of its volume of saturated mag-
nesium sulphate solution. The plasma may then be conveniently
separated from the corpuscles by means of a centrifugal machine.
Again, two ligatures may be placed on a large bloodvessel, so that
a portion of it can be excised full of blood and suspended vertically
(the so-called experiment of the ' living test-tube ') ; coagulation
is long delayed, and the corpuscles sink to the lower end. In these
and many other ways plasma free from corpuscles can be got ; and
it is found that when the conditions which restrain coagulation are
removed — when, for instance, the temperature of the horse's plasma
is allowed to rise or the magnesium sulphate plasma is diluted with
several times its bulk of water — clotting takes place, with forma-
tion of fibrin in all respects similar to that of ordinary blood-clot.
The corpuscles themselves cannot form a clot.* From this we con-
clude that the essential process in coagulation of the blood is the
formation of fibrin from some constituent of the plasma, and that
the presence of corpuscles in ordinary blood-clot is accidental.
In accordance with this conclusion, we find that lymph entirely
free from red corpuscles clots spontaneously, with formation of
fibrin ; and when fibrin is removed from newly shed blood by whip-
ping it with a bundle of twigs or a piece of wood, it will no longer
coagulate, although all the corpuscles are still there.
What, now, is the substance in the plasma which is changed into
fibrin when blood coagulates ? If plasma, obtained in any of the
ways described, be saturated with sodium chloride, a precipitate is
thrown down. The filtrate separated from this precipitate does not
coagulate on dilution with water; but the precipitate itself — the
so-called plasmine of Denis — on being dissolved in a little water,
does form a clot. Fibrin is therefore derived from something in
this precipitate. Now, ' plasmine ' contains two protein bodies —
fibrinogen, which coagulates by heat at about 56° C., and serum-
globulin, which coagulates at about 75° C., and it was at one time
believed that both of these entered into the formation of fibrin
(Schmidt). Hammersten, however, has shown that fibrinogen alone
is a precursor of fibrin; pure serum-globulin neither helps nor
hinders its formation. This observer isolated fibrinogen from blood-
plasma by adding sodium chloride till about 13 per cent, was
present. With this amount the fibrinogen is precipitated, while
serum-globulin is not precipitated till 20 per cent, of salt is reached.
After precipitation of the fibrinogen, the plasma no longer coagu-
lates; and a solution of pure fibrinogen can be made to clot and
to form fibrin, while a solution of serum-globulin cannot. Blood-
* Bird's corpuscles, however, washed free from plasma, will form a clot
when laked in various ways, as by addition of water or by freezing and
thawing.
COAGULATION 35
serum, too, which contains abundance of serum-globulin, but no
fibrinogen, will not coagulate.
So far, then, we have reached the conclusion that fibrin is formed
by a change in a substance, fibrinogen, which can be obtained by
certain methods from blood-plasma. It may be added that there
is evidence that fibrinogen exists as such in the circulating blood;
for if unclotted blood be suddenly heated to about 56° C., the tem-
perature of heat-coagulation of fibrinogen, the blood for ever loses
its power of clotting. The liver seems to be an important place of
origin of fibrinogen, which may also be formed in the bone-marrow.
That the liver is intimately concerned in the production of fibrinogen
is indicated by a number of facts. In phosphorus poisoning, and
notably in poisoning by chloroform, which causes necrosis, especially
of the central portions of the hepatic lobules, the amount of
fibrinogen in the blood is quickly diminished. The diminution is
proportional to the extent of the injury to the liver, and the blood
loses more or less completely its power of clotting. If the injury
is repaired, the fibrinogen is rapidly regenerated (Whipple) . If the
blood is allowed to circulate for a time in the head and thorax of
an animal without passing into the rest of the animal's body, it
becomes incoagulable, and the fibrinogen is found to be markedly
deficient in amount. When the blood of an animal is defibrinated
by whipping, and reinjected, regeneration of the fibrinogen does
not occur if the liver has been eliminated, whereas it takes place
rapidly if the liver is intact (Meek) .
Since fibrinogen is readily soluble in dilute saline solutions, and
fibrin only soluble with great difficulty, we may say that in coagu-
lation of the blood a substance soluble in the plasma passes into an
insoluble form. How is this change determined when blood is
shed ? We have said that a solution of pure fibrinogen can be
made to coagulate, but it does not coagulate of itself. The addition
of another substance in minute quantity is necessary. This sub-
stance, to which the name thrombin has been applied, can be
obtained in various ways, although not in a state of purity; for
example, by precipitating blood-serum, or defibrinated blood, with
fifteen to twenty times its bulk of alcohol, letting the whole stand
for a month or more, and then extracting the precipitate with
water. All the ordinary proteins of the blood having been ren-
dered insoluble by the alcohol, the thrombin passes into solution
in the water, and the addition of a trace of the extract to a solution
of fibrinogen causes coagulation. When purified as well as possible,
thrombin still gives protein reactions, but it is not known whether
it is really a protein.
The action of thrombin on fibrinogen helps to explain many
experiments In coagulation. Thus, transudations like hydrocele
fluid do not clot spontaneously, although they contain fibrinogen,
36 THE CIRCULATING LIQUIDS OF THE BODY
which can be precipitated from them by a stream of carbon dioxide
or by sodium chloride. But the addition of a little thrombin
causes hydrocele fluid to coagulate. So does the addition of serum,
not because of the serum-globulin which it contains, as was once
believed, but because of the thrombin in it. The addition of blood-
clot, either before or after the corpuscles have been washed away,
or of serum-globulin obtained from serum, also causes coagulation
of hydrocele fluid, and for a similar reason, the thrombin having a
tendency to cling to everything derived from a liquid containing
it. On the other hand, serum which, although thrombin is present
in it, does not of itself clot, because the fibrinogen has all been
changed into fibrin during coagulation of the blood, can be made
to coagulate by the addition of hydrocele fluid, which contains
fibrinogen. We have thus arrived a step farther in our attempt to ex-
plain the coagulation of the blood: it is essentially due to the formation
of fibrin from the fibrinogen of the plasma under the influence of
thrombin. Up to this point there is agreement between physiologists.
Some difference of opinion exists, however, as to the manner in
which thrombin is formed or activated when blood is shed, aud a?
to the nature of its action upon fibrinogen once it is fully formed.
The Formation of Thrombin from its Precursors. — There is good
reason to believe that thrombin is formed by the interaction of three
factors: (i) A substance which, since it is a precursor of thrombin,
is called thrombogen, or prothrombin. It is already present in the
circulating plasma. (2) A substance liberated from the formed ele-
ments of the shed blood, but which can be obtained also from the
cells of all tissues. Since it has been supposed to act upon throm-
bogen, changing it into fully formed thrombin, much in the same
way as enterokinase (p. 370) acts upon trypsinogen, changing it
into fully formed trypsin, it is called thrombokinase (Morawitz).
(3) Calcium ions. The following experiments illustrate the role of
these three factors:
The plasma obtained by drawing off bird's blood — e.g., the blood of a
fowl or goose — through a perfectly clean cannula into a perfectly clean
vessel, without contact with the tissues, and then rapidly centrifugal-
izing off the formed elements, can be kept unclotted for days and even
weeks. The addition of a small amount of tissue extract (procured by
rubbing up blood-free liver, thymus, muscle, or other organs with sand,
and extracting for several hours with salt solution) to the bird's plasma
causes rapid coagulation. The plasma contains thrombogen and
calcium salts, but is lacking in thrombokinase, which is supplied by the
tissue extract. A solution of fibrinogen containing calcium will clot
if serum, in which fibrin -ferment is always present, be added. It will
not clot on addition of tissue-extract alone, nor on addition of bird's
plasma alone (obtained as above), but will readily coagulate if both
tissue extract and bird's plasma be added. Therefore, something in
the bird's plasma (thrombogen), plus something in the tissue extract
(thrombokinase), produce in the presence of calcium the same effect as
the thrombin of serum. It can be shown that calcium is only necessary
COAGULATION 37
for the formation of the thrombin, but not for its action on fibrinogen.
For instance, a calcium-free solution of fibrinogen can be made to clot
by serum from which the calcium has been removed.
If a soluble oxalate (potassium or ammonium oxalate) is mixed with
freshly drawn dog's blood to the amount of o'2 or o'3 percent., the blood
remains unclotted. The plasma separated from this oxalated blood
contains both thrombogen and thrombokinase, but it does not coagu-
late, because the calcium has been precipitated out in the form of in-
soluble calcium oxalate. In the absence of calcium the reaction of the
thrombogen and thrombokinase which leads to the formation of
thrombin does not take place. All that is necessary to bring about
coagulation is to add calcium chloride in somewhat greater quantity
than is required to combine with any excess of oxalate present. If more
than a certain amount of calcium be added, clotting is hindered instead
of being helped, so that it is only within certain limits of concentration
that calcium favours coagulation. From oxalate plasma a nucleo-
protein or a mixture of nucleo-proteins can be separated which contains
thrombogen and thrombokinase, but little or no calcium, and does not
cause clotting, but which on treatment with a calcium salt acquires the
properties of thrombin.
When sodium fluoride is added to freshly drawn blood to the amount
of o'3 per cent., coagulation is also prevented. But there is this differ-
ence between oxalate and fluoride plasma — that, although the calcium
has been precipitated in both, the addition of calcium chloride to fluoride
plasma is not sufficient to induce clotting. Tissue extract containing
thrombokinase must be supplied as well. In some way or other sodium
fluoride interferes with the liberation of thrombokinase from the formed
elements of the blood, although in the concentration mentioned it does
not hinder the action of fully formed thrombin, as is shown by the fact
that fluoride plasma coagulates on the addition of a little serum, which
supplies thrombin. The fluoride blood clots readily if it is diluted with
water, and at the same time mixed with calcium chloride solution, for
the water damages the formed elements, and thus favours the liberation
of thrombokinase.
Sodium citrate solution prevents the coagulation of blood run into
it, although there is no precipitation of the calcium. The addition of
calcium chloride to citrate plasma induces clotting, and the action of
the citrate is assumed to be due to the formation of a compound with
the calcium of the blood, which does not dissociate so as to yield calcium
ions. It ought to be remarked, however, that in all so-called decalci-
fied plasmas, as ordinarily obtained, blood-platelets are present, and
that platelets disintegrate under the influence of calcium salts. It
has been shown, indeed, that many of the reagents and procedures
which hinder the clotting of shed blood also prevent the breaking up of
the platelets. Thus, the cooling of the blood, the addition of hirudin,
sodium oxalate, sodium citrate, manganese salts, etc., which are
classical methods used in obtaining platelets for microscopical study,
are also classical methods of hindering coagulation. These facts have
not hitherto been sufficiently taken account of in interpreting experi-
ments on decalcified blood. They indicate that the decalcifying agents
may hinder clotting by interfering with the liberation of essential sub-
stances from the platelets, and that this may be the decisive factor, and
not merely the withdrawal of the calcium from the field where the
already liberated thrombokinase and thrombogen would otherwise
react to form thrombin.
When proteoses (or peptones) are injected into the circulation of a
dog or goose, the blood is deprived of the power of coagulation. The
38 THE CIRCULATING LIQUIDS OF THE BODY
peptone plasma must be assumed to contain both thrombogen and
thrombokinase, since it can be made to clot in various ways (e.g., by dilu-
tion with water or by slight acidulation with acetic acid) without the
addition of anything which could supply either of these factors. Yet
a little tissue extract causes it to clot much more rapidly than simple
dilution or acidulation, and more rapidly than the addition of serum.
So that either the thrombokinase already present in peptone plasma is
present in an unavailable form, or in some way the formation of throm-
bin from its precursors is hindered. But this is not the only cause of
the incoagulability of peptone plasma. It may be shown to contain
an antithrombin, a body which antagonizes the action of fully formed
thrombin, and which does not seem to be a ferment, since it acts quan-
titatively in proportion to the amount present. This is the reason why,
although peptone plasma can always be made to clot by the addition
of fibrin ferment, in serum, for instance, relatively large quantities of
it must be supplied (Practical Exercises, pp. 64, 65).
Fig. 5. — Fibrin Formation in Horse's Plasma (Ultramicroscope) (Stiibel). Several
clumps of disintegrated platelets from which the fibrin filaments radiate.
An extract of the head of the medicinal leech in salt solution prevents
the clotting of blood both in the test-tube and when injected into the
circulation. The plasma obtained differs from peptone plasma in
refusing to coagulate unless tissue extract is added. It is therefore
deficient in thrombokinase, or, rather, as has been shown, the kinase
present is unable to act, because neutralized by antikinase present in the
leech extract. Leech extract also contains an antithrombin, which can
be neutralized by a sufficient amount of thrombin. In the small
wound from which the leech sucks blood this sufficient amount is not
present, and the blood remains unclotted, as it also does in the alimen-
tary canal of the leech. The anticoagulant substance, hirudin, has
been isolated, and gives the reactions of an albumose.
Sources of Thrombogen and Thrombokinase. — It has already been
stated that thrombogen exists in the circulating plasma. This is
shown by the fact that fluoride plasma obtained from blood drawn
directly through a wide cannula into sodium fluoride solution, with
COAGULATION
all precautions to prevent alteration of the blood, and immediately
separated from the formed elements by the centrifuge, will clot
on the addition of tissue extract. The source of the thrombogen
has been thought to be the blood-plates, but this has not been
proved. Thrombokinase is not present in the circulating plasma.
In shed and clotting blood which has not been allowed to come into
contact with cut tissues, the only possible sources of thrombokinase,
so far as we know, are the corpuscles and the blood-plates. The
red corpuscles we may at once dismiss, for although the stromata,
especially of nucleated corpuscles, contain thrombokinase, or can
under artificial conditions be made to develop that action on
coagulation by which we recognize its presence, not only do they
remain intact under ordinary circumstances during coagulation,
but there is strong evidence, as
has already been pointed out,
that they do not make any essen-
tial contribution to the process.
We have left over the leucocytes
and the platelets, and it is highly
probable that from the platelets
thrombokinase is liberated in the
first moments after blood is
drawn, and, acting on the throm-
bogen already present in the plas-
ma, changes it into actual throm-
bin. This surmise is strengthened
by the fact that in freshly shed
mammalian blood extensive de-
struction of blood-plates takes
place. Viewed with the ultra-
microscope, the blood-platelets,
in a drop of clotting plasma,
which are at first homogeneous in appearance (optically empty),
become granular. Then the platelets begin to agglutinate and
swell up, and the agglutinated platelets are transformed into clumps
of granules, from which needles of fibrin shoot out. Other needles
and filaments of fibrin form in contact with the glass or free in
the plasma, and soon the field is occupied by a felt-work of
fibrin. The leucocytes have not been observed to be related to the
process, at least, in the blood of mammals (Stiibel). It is true that
the white layer or ' buffy coat ' which tops the tardily formed clot
of horse's blood, and consists of the lighter, and therefore more
slowly sinking colourless cells, causes clotting in otherwise in-
coagulable liquids like hydrocele fluid much more readily than the
red portion of the clot, and yields far more thrombin on treatment
with alcohol. It can also be easily verified that in mammalian
Fig. 6. — Fibrin Formation in Plasma from
a Case of Haemophilia (Ultramicro-
scope) (Stiibel). The needles of fibrin
are slowly formed, and very large.
40 THE CIRCULATING LIQUIDS OF THE BODY
blood collected in paraffined vessels, so as to delay clotting, and
immediately centrifugalized, coagulation begins in and around the
layer of white elements, and then spreads upwards in the stratum
of plasma and downwards in the stratum of erythrocytes. But in
this white upper layer platelets are always intermingled with leuco-
cytes. It has been shown, however, that the blood of the cray-
fish, which coagulates with extreme rapidity, contains certain
colourless corpuscles, which immediately it is withdrawn, break
up with explosive suddenness, and that substances which hinder
the breaking up of these corpuscles restrain coagulation (Hardy).
In the blood of another crustacean Limulus, the kingcrab, coagula-
tion is preceded by an agglutination of the leucocytes which exhibit
amoeboid movements. They become entangled by the interlacing
of the pseudopodia which they protrude (L. Loeb).
The disintegration of the platelets in shed blood has been attributed
by Deetjen to an increase in the alkalinity of the blood, by escape
of carbon dioxide, it may be. When blood is placed on a quartz
slide and covered with a quartz cover-slip, the platelets, according
to this observer, do not break up ; but if they are brought into con-
tact with a medium whose OH — concentration is raised ten times
or more above that of freshly drawn blood (still only a weak alka-
line reaction), disintegration ensues. He supposes that the contact
of glass acts harmfully on account of the alkali in it. It is im-
possible to say at present whether this observation has any bearing
on normal coagulation.
Thrombokinase has been shown to exist not only in the leuco-
cytes, the platelets, and the stromata of the coloured corpuscles, but,
as already stated, in all tissues hitherto examined. Under ordinary
circumstances it appears that a larger amount of thrombogen is
liberated or is already present in shed blood than can be changed
into thrombin by the thrombokinase set free, since serum contains
a surplus of thrombogen in addition to the fully formed ferment.
This is shown by the fact that the activity of a given quantity of
serum in causing the coagulation of a plasma not spontaneously
coagulable or of a fibrinogen solution is increased by the addition
of tissue extract (containing thrombokinase).
The thrombin of any particular kind of vertebrate blood has no
marked specific action — that is, will cause coagulation in solutions of
fibrinogen or plasma of very different origin. For example, the
sera of all vertebrates hitherto investigated induce clotting in
goose's plasma. On the other hand, it appears that a greater degree
of specificity exists in the case of the thrombokinase and throm-
bogen, the specificity being absolute in some cases, relative in others.
That is to say, the thrombokinase of one animal may activate the
thrombogen of an animal of another group, while it may fail to
activate the thrombogen of an animal belonging to a third group.
COAGULATION 41
But it will always activate the thrombogen of an animal of the
same kind.
To sum up, we may say that when blood is shed, thrombin is rapidly
formed by the action of thrombokinase, liberated from the leucocytes,
the blood-plates, and possibly to some extent from the erythrocytes,
upon thrombogen, already present in the circulating plasma. Further
— and this is of great practical importance — since no vessel is opened
under ordinary circumstances except through a wound in the overly-
ing structures, the cut tissues supply a store of thrombokinase at
the point where it is required to aid in the stanching of the wound.
Calcium is essential to the reaction by which thrombogen and thrombo-
kinase form thrombin, but is not necessary for that action of thrombin
on fibrinoges by which fibrin is produced (Practical Exercises,
pp. 62-65).
The Nature of the Action of Thrombin on Fibrinogen. — The usual
view, first advanced by Schmidt many years ago, is that thrombin
acts as an enzyme. Hence it is often spoken of as fibrin- ferment.
In support of this theory it has been stated that the thrombin
does not itself seem to be used up in the process, nor to enter bodily
into the fibrin formed; that a small quantity of it can cause an
indefinitely large amount of fibrinogen to clot; and that its power
is abolished by boiling (p. 335). There has been a disposition
among more recent observers to question this evidence. Accord-
ing to Rettger, the quantity of fibrin formed when a small amount of
thrombin is added to a fibrinogen solution tends to a fixed maxi-
mum, which does not increase with the time of action.* Under
certain conditions, also, it is said that thrombin is not destroyed at
the temperature of boiling water. Whatever the precise nature of
the reaction which leads to the precipitation of the fibrinogen in the
form of fibrils, thrombin is very loosely combined if combined at
all in the fibrin, since it is readily extracted by an 8 per cent,
solution of sodium chloride. This, indeed, is one of the best ways
of obtaining an active thrombin solution.
The view which we have followed above, in accordance with
Morawitz, that the substances in tissue extracts which favour
coagulation do so by activating prothrombin to fully formed
thrombin, has also been opposed by a number of the more recent
workers. Some consider that they exert a direct action upon
fibrinogen similar to, although not necessarily identical with, that
of thrombin, and speak of them as coagulins (L. Loeb). Howell
holds that these substances, which he prefers to term thromboplastic
substances, since this makes no assumption as to their mode of
action, play a quite different role, namely, that of neutralizing anti-
thrombin. His observations have led him to the conclusion that
* The inquiry is complicated by the fact that fibrin, once formed, tends to
adsorb the remaining thrombin and so tc interfere with its further action.
42 THE CIRCULATING LIQUIDS OF THE BODY
the effective thromboplastic substance in the tissues is a phos-
phatide, probably kephalin, united with protein.
Intravascular Coagulation Regulation of the Clotting Process,
or Thrombotaxis.— So far we have been considering the problem
of coagulation as if all the data for its solution could be
obtained by a study of the blood itself. In other words, our main
business up to this point has been the explanation of coagulation
in the shed blood; it has been only incidentally, and with the object
of casting light on the question of extravascular clotting, that we
have touched on the coagulation of the blood within the living
vessels. It is not possible here to adequately discuss, nor even to
define, the differences between the two problems. All we can do
is to warn the student, and to emphasize the warning by one or
two illustrations, that valuable as is the knowledge derived from
experiments on extravascular coagulation, it would be totally mis-
leading if applied without modification to the circulating blood.
For instance, we have recognized in the blood-plates an important
source of the thrombokinase which plays so great a part in the
clotting of shed blood; but we may be sure that blood-plates are
constantly breaking down in the lymph and the blood, and we have
to inquire how it is that coagulation does not occur, except in
disease, within the vessels. Calcium is not wanting to the circu-
lating plasma, fibrinogen is not wanting, and it has already been
mentioned that thrombogen exists in perfectly fresh and, as we
may say, still living blood. Why, then, does it not coagulate ?
Some have said that coagulation is ' restrained ' by the contact of
the living walls of the bloodvessels; but although it is certain that
the contact of foreign matter — and all dead matter is foreign to
living cells — does hasten the destruction of blood-plates or that
alteration in them on which the liberation of the precursors of the
ferment depends, it is evident that it is just this ' restraining ' in-
fluence of the vessels, if it is due to anything more than the mere
smoothness of their endothelial lining, which has to be explained.
The best answer which can be given to the question is: First, that
the quantity of thrombokinase free in the plasma at any given time
must be small, since no evidence of its presence in fluoride plasma
can be obtained. If thrombokinase is liberated in the circulating
blood, we may assume that it is changed into some inactive sub-
stance, or quickly eliminated. And it appears that, unlike the true
ferments, thrombokinase acts quantitatively — i.e., in proportion to
its amount — upon thrombogen. Second, an antithrombin exists
in the circulating plasma, and even if fully formed fibrin-ferment
were present, it could not cause coagulation until the antithrombin
had been neutralized. This antithrombin is probably not manu-
factured in the blood, or at least not exclusively in the blood, but
in the tissues, and there is no reason to deny the vessels themselves
COAGULATION 43
a share in its production, even if its presence has not hitherto been
demonstrated in the internal coat (L. Loeb) . So that living blood
within the living vessels may be said to be acted upon by two sets
of influences, one tending to favour coagulation, the other to oppose
it. In the clotting of extravascular plasma, free from corpuscles,
we may indeed see the continuation, under modified conditions, of
a normal process always going on within the bloodvessels. Under
normal conditions, the processes that make for coagulation never
obtain the upper hand.
Indeed the margin of safety within which what may be called
the thrombo-regulative mechanism works seems to be surprisingly
wide, and the equilibrium in the circulating blood far more stable
than observations on clotting outside of the body might lead us to
suppose. Very considerable quantities of thrombin or of de-
fibrinated blood or serum containing thrombin can be injected into
the blood-stream without ill effect. According to Ho well, the
presence of the abnormally great amount of thrombin causes the
formation of sufficient antithrombin to neutralize it, probably by a
protective reflex secretion. In like manner the injection of tissue
extracts or a solution of thrombo plastic substance (thrombokinase)
prepared from them by precipitation does not necessarily induce
coagulation in the vessels. On the contrary, when injected slowly
or in small amount into the veins of an animal, it abolishes for a
time the power of coagulation of the blood; and when this ' nega-
tive phase,' as it is called, has been once established, even a very
large and rapid injection produces no further effect, possibly because
an antibody which neutralizes the action of thrombokinase has
been produced. In both cases the limits of safety can be over-
stepped, and intravascular clotting induced by the injection either
of thrombin or of thrombokinase. When a considerable quantity
of the active substance in tissue extract is introduced at the first
injection, extensive coagulation in the vessels instantly ensues; the
animal dies in a few minutes; and the right side of the heart, the
venae cavae, the portal vein, and perhaps the pulmonary arteries,
may be found choked with thrombi. Here the injected thrombo-
kinase is responsible for the clotting, thrombogen and calcium being
already present. Curiously enough, intravascular coagulation fails
to be produced in a certain proportion of cases when albino animals
are injected with material from pigmented animals, while there is
no absolute failure of coagulation when albinos are injected with
material from albinos, and no failure when pigmented animals are
injected with material either from other pigmented animals or from
albinos. Intravascular coagulation on injection of tissue extracts
is especially striking in birds.
To a certain extent the action of tissue extracts in coagulation
can be imitated by other substances of animal origin, such as the
44 THE CIRCULATING LIQUIDS OF THE BODY
venoms of some vipers (Martin). It is not known whether these
substances act on the blood-plates, leucocytes, or other cells, and
thus cause an increased production or an increased liberation of
one or more of the precursors of thrombin, or whether they take
part directly in its formation. But there is some evidence that
the venoms which favour coagulation do so in virtue of their con-
taining a kinase. On the other hand, cobra- venom prevents coagula-
tion by means of an antikinase — that is, a substance which antago-
nizes the action of kinase, and so hinders the formation of thrombin.
It does not contain an antithrombin — that is, a body which will
prevent the action of thrombin already formed (Mellanby).
Relation of the Liver to Coagulation.— It is not known with any
degree of certainty whether the thrombo-regulative processes are
especially associated with any particular organ. But there are
facts which suggest that the relations of the liver to the coagulation
of the blood are peculiarly close. Not only, as previously shown,
does it take an important share in the formation of fibrinogen, but
there is some evidence that it is closely related to the formation
of antithrombin. We have already mentioned that the injection
of commercial peptone, which consists chiefly of proteoses, into
the blood of dogs causes it to lose its coagulability. The effect
gradually passes away, till after some hours the original power of
coagulation is restored (p. 63). The liver is known to be intimately
concerned in the production of this remarkable result, for if the
circulation through it be interrupted, the injection of proteose is
ineffective. Further, if a solution of proteose is artificially
circulated through an excised liver, a substance (perhaps an anti-
thrombin) is formed which is capable of suspending the coagula-
tion of blood outside of the body, a property which proteoses them-
selves do not possess, or possess only in slight degree. It is not
believed that the proteose is actually changed into this anticoagu-
lant substance, but rather that the liver cells produce it as a
' reaction ' to the presence of the foreign substance, being perhaps
stimulated in some way by the circulating proteose. In part the
abnormally great alkalinity of the peptone blood, due to the excess
of alkali secreted by the liver, is responsible for its slow coagulation.
Under certain conditions, some of which are known and others not,
the injection even of one or other of the purified proteoses causes
not retardation, but hastening, of coagulation; and if this has been
the result of a first injection, a second is equally unsuccessful. It
is possible that by an effort of the organism to restore the normal
coagulability of the blood, on which its very existence depends,
substances which favour coagulation are produced, and that the
result of an injection of proteose is determined by the relative
amount of coagulant and anticoagulant secreted in a given time.
Protamins (products obtained from the ripe milt of certain fishes,
COAGULATION 45
and believed to be the simplest proteins) exert, when injected
intravenously, a retarding influence on coagulation, and lower the
blood-pressure,, just as albumoses do (Thompson). Even serum-
albumin and serum-globulin possess this property in some degree.
All these substances also cause a diminution in the number of
leucocytes in the blood owing, in the case of albumose at any rate,
to their accumulation in the abdominal vessels, and not to any
actual destruction of them.
It has been lately announced that the adrenal glands have a relation
to the coagulation of the blood. Stimulation of the splanchnic nerve,
which supplies secretory fibres to the adrenal, greatly hastens coagula-
tion, but has no such effect if the adrenal on the corresponding side
has been previously removed (Cannon). It is possible that this effect
is exerted through the liver, since it is known that one important
function of the liver, the regulation of the sugar content of the blood,
is intimately dependent upon the adrenal, and is affected by excitation
of its splanchnic nerve-supply.
In certain pathological conditions the normal balance of the factors
that make for clotting and prevent it may be upset, and the scales may
tip in either direction. In patients suffering from the formation of
spontaneous clots in the veins (thrombosis) it is stated that the anti-
thrombin in the blood is diminished, the amount of prothrombin being
normal. The mere slowing of the blood-stream in conditions where
the circulatory mechanism is enfeebled may favour thrombosis. For
anything which cripples the circulation, and consequently limits the
free interchange between blood and tissues, interferes with the elimina-
tion or neutralization of the precursors of thrombin, and with the
entrance of the substances that render the fully formed thrombin in-
active. This, as well as the injury caused by the ligature, which may
favour the passage of thromboplastic substances into the lumen of the
occluded vessel, is a possible factor in the formation of the clot
on which the surgeon relies for the permanent sealing of ligated
vessels.
In haemophilia, a disease in which the coagulation of the blood is
characteristically slow, and in which even slight wounds may occasion
. severe or fatal haemorrhage, the thrombogen (prothrombin) has been
found deficient in amount, and the injection of normal serum or the
transfusion of normal blood has been used with temporary advantage
in the treatment of the condition. In certain cases of purpura, how-
ever, where haemorrhage also occurs with abnormal ease, no variation
from the normal could be detected in the content of either antithrombin
or prothrombin (Ho well). Some have supposed that in such conditions
the fault is an unnatural fragility of the small vessels rather than a
deficiency in the power of the blood to clot, but of this also no actual
evidence has been adduced. Another factor on which the promptness
and completeness of the sealing of wounded vessels may depend has been
recently brought into notice, namely —
The Vaso-Constrictor Property of Shed Blood. — It has been shown
that when blood is shed and no precautions are taken to prevent
clotting, it very quickly develops the power of causing marked
constriction of bloodvessels. This can be demonstrated by allow-
ing the serum to act on rings cut from arteries (Practical Exercises,
46
THE CIRCULATING LIQUIDS OF THE BODY
p. 66), or by perfusing the hind-legs of frogs with a saline solu-
tion containing serum. Plasma derived from blood in which the
platelets have been prevented from breaking down, and which
therefore remains unclotted, has no such effect, or a much slighter
Fig. 7. — Sheep Artery Rings. At 14 and 16 Ringer's solution was replaced by citrate
plasma (two different specimens). At 15 and 17 the plasmas were replaced by
the corresponding sera. At 18 and 19 the sera replaced Ringer's solution directly.
Time-trace, half-minutes. Tracings reduced to J.
effect. But when the platelets are separated from the plasma
and then decomposed, the resulting extracts of platelets are rich
in vaso-constrictor material. In the sealing of wounded vessels
the platelets would therefore appear to play a double role, yielding
Fig 8. — Frog Perfusion Experiment with Serum. The drops of liquid flowing through
the preparation are recorded. At n citrate plasma was injected; at 13 the
corresponding citrate serum. The tracing is to be read from left to right.
Time is marked in half -minutes.
a substance which causes constriction of the vessel in the neigh-
bourhood of the wound while a plug of clot is being formed, thanks
to other substances liberated from the platelets, which take an
essential part in coagulation. The vaso-constriction may perhaps
VASO-CONSTRICTOR PROPERTY OF SHED BLOOD
47
be looked upon as a form of ' first aid ' to diminish the haemor-
rhage, and also to make it less easy for the beginning clot to be
washed away. It is obvious that the two processes would be
mutually advantageous in dealing with those injuries of the vascular
system on the prompt repair of which the very existence of the
"A /v-
-Ar-
Z-LsjL. ~+\ ^
\l
\ z
x^
Jc.c Serum* citrate
/cc Plasma
/cc Plasma Id Seru/r'cUraie
Fig. 9. — Frog Perfusion Experiment with Serum. Curves showing the flow. The
number of drops per half-minute is laid off along the vertical axis, and the time
(in half-minutes) along the horizontal axis; 38 drops correspond to i c.c.
organism at all times depends, and it is not without interest to
find that special formed elements in the blood, the platelets, are
pre-eminently associated with both processes.
SECTION III. — THE CHEMICAL COMPOSITION OF BLOOD.
The serum of coagulated blood represents the plasma minus
fibrinogen; the clot represents the corpuscles plus fibrin. Thus:
Plasma - Fibrin (o gen) = Serum.
Corpuscles + Fibrin = Clot.
Plasma + Corpuscles — Serum +Clot
Blood.
Bulky as the clot is, the quantity of fibrin is trifling (0-2 to 0-4 per
cent, in human blood). The plasma contains about 10 per cent,
of solids, the red corpuscles about 40 per cent., the entire blood
about 20 per cent.
Serum contains 7 to 8 per cent, of proteins, about 0-8 per cent,
of inorganic salts, and small quantities of neutral fats, soaps,
cholesterin esters, lecithin, dextrose, urea, lactic acid, glycuronic
acid, amino - acids,
Solids
Cor/7usdes[~
and other sub-
stances. The chief
proteins are serum-
albumin and serum-
globulin. In the rab-
bit the former, in
the horse the latter, is the more abundant ; in man they exist in not
far from equal amount. A small quantity of nucleo -protein and of
fibrino-globulin (which some consider a soluble product formed from
Plasm*
Fig. 10. — Diagram showing Relative Quantity of Solids
and Water in Red Corpuscles and Plasma.
48 THE CIRCULATING LIQUIDS OF THE BODY
nbrinogen in clotting) is also present. Ferments which cause
hydrolysis of proteins and carbohydrates, a ferment (lipase) which
acts upon fats, and certain oxidizing ferments (oxydases), have also
been demonstrated. The chemical nature of the bodies which
confer on serum or plasma its specific haemolytic, agglutinating,
precipitating, and bactericidal properties has not been definitely
determined.
The quantitative composition of serum, especially as regards the
inorganic salts, is remarkably constant in animals of the same species,
and even in animals of different species belonging to the same, or to
not very widely separated, natural groups. In cold-blooded animals
the serum-albumin is scantier than in mammals, the globulin relatively
more plentiful.
Serum-albumin belongs to the class of native albumins. It has
been obtained in a crystalline form from the serum of horse's blood. It
Fig. ii. — Perspective View of Vivi-Diffusion Apparatus (Abel). This form of the
apparatus contains sixteen tubes. A, arterial cannula; B, venous cannula;
C, side tube for introduction of hirudin; D, inflow tube; E, outlet tube for the
blood; F, G, supporting rod attached at H and K to branched V-tubes; L, burette
for hirudin; M, N, tube for filling and emptying liquid in outer jacket; O, air
outlet; P, dichotomous branching-point of inflow tube; Q and R, quadruple
branching-points of the same ; S, S, wooden supports; T, thermometer. At
each of the points H and K the blood is collected from four tubes into one,
bending round to the back, and there redividing into four return flow tubes.
Arrows show the direction of the flow.
is soluble in distilled water, and is not precipitated by saturating its
solutions with certain neutral salts. Heated in neutral or slightly
acid solution, it coagulates first at 73°, then at 77°, then at 84° C.
Although this is not of itself sufficient proof, there is other evidence
that it consists of a mixture of proteins.
Serum-globulin, also called paraglobulin, belongs to the globulin
group of proteins. When heated, it coagulates at about 75° C. (p. 9).
It is insoluble in distilled water, and is precipitated by saturation with
such neutral salts as magnesium sulphate, or by half -saturation with
ammonium sulphate. It appears that, as thus obtained, it is not a
single substance, but a mixture of at least two proteins — eu-globulin,
CHEMICAL COMPOSITION OF BLOOD
49
which can be precipitated from its saline solution by dialyzing off the
salts, and pseudo-globulin, which cannot be so precipitated.
In addition to the nitrogen represented as protein, serum (or plasma)
contains non-protein nitrogen, the amount of which varies with the
nature of the food and the stage of digestion. Part of this fraction is
attributable to urea and other metabolites on their way to be excreted,
but another portion, and an important one, is due to amino-acids
absorbed from the intestine during the digestion of proteins and on
their way to be utilized in the tissues.
Of the inorganic salts of serum, the most important are sodium
chloride and sodium bicarbonate. Small amounts of potassium,
calcium, and magnesium, united with phosphoric acid or chlorine, and
a trace of fluoride, are also present. A portion of the salts is loosely
combined with the proteins.
Our knowledge of the chemistry of the circulating plasma is likely
to be notably augmented .by the method of vivi-diffusion recently intro-
duced by Abel. An artery of an anaesthetized animal is connected by
a cannula to a system of celloidin tubes immersed in a saline solution.
Blood passes from the artery through the tubes, where it exchanges
diffusible constituents with the solution, and is then returned to the
animal's body by another cannula attached to a vein. Coagulation
of the blood in the apparatus is prevented by hirudin, and under
aseptic conditions the circulation may proceed through the tubes for a
long time. The saline solution can then be analyzed for substances which
have entered it from the blood — amino-acids, for example (Fig. n).
The following tables give some details of the composition of blood :
1,000 GRAMMES OF PIG'S BLOOD (CORPUSCLES, 435*09; SERUM, 564*91)
CONTAINED
Corpuscles.
Serum.
Corpuscles.
Serum.
Water
272'2O
5l8*36
P2O5 as nuclein
0-0455
O-OI23
Solids
162-89
46*54
Na2O . .
*
2-401
Haemoglobin
I42'2O
K2O . .
2-157
0-152
Protein
8*35
38-26
Fe203
0-696
Sugar
0-684
CaO
0-0689
Cholesterin
0-213
0-231
MgO ..
0-0656
0-0233
Lecithin
1-504
0-805
Cl
0-642
2-048
Fat . .
1-104
P205 ..
0-895
O-III
Fatty acids
0-027
0-448
Inorganic P2O5
0-719
0-296
PROTEINS OF PLASMA IN 1,000 GRAMMES.
Albumin.
Globulin.
Fibrinogen.
Total.
Man
40-I
28-3
4-2
72-6
Dog
31-7
22-6
6-0
60-3
Sheep
38-3
30-0
4-6
72-9
Horse
28-0
47*9
4*5
80-4
Pig
44-2
29-8
6*5
80-5
* The pig's erythrocytes are peculiar in that the sodium appears to be
entirely confined to the plasma.
5<> THE CIRCULATING LIQUIDS OF THE BODY
The Coloured Corpuscles consist of rather less than 60 per cent, of
water and rather more than 40 per cent, of solids. Of the solids the
pigment haemoglobin makes up about 90 per cent. ; the proteins and
nucleo-protein of the stroma about 7 percent.; lecithin and choles-
terin 2 to 3 per cent. ; inorganic salts (which vary greatly in their
relative proportions in different animals, but in man consist chiefly
of phosphates and chloride of potassium, with a much smaller
amount of sodium chloride) about i per cent. Potassium has been
demonstrated microchemically in frog's erythrocytes (Macallum)
(Frontispiece] . There is evidence that a portion of the salts is more
firmly combined than the rest, so that, even after the action of the
most energetic laking agents, this fraction remains attached to the
stroma. The erythrocytes of some animals — e.g., the dog — contain
dextrose. When dextrose -is added to human blood it rapidly dis-
tributes itself over corpuscles and plasma (Rona), although not
exactly in proportion to their respective volumes (Masing). Hither-
to the dextrose in blood has been reckoned as if it all belonged to the
plasma.
Hemoglobin. — Of all the solid constituents of the blood, haemoglobin
is present in greatest amount, constituting as it does no less than
13 per cent., by weight, of that liquid. It is an exceedingly complex
body, containing car-
D c bon, hydrogen, nitro-
WA gen, and oxygen in
much the same pro-
portions in which they
exist in ordinary pro-
teins (p. i). Iron is
also present to the ex-
Pig. 12.— Diagram of Spectroscope. A, source of light ; tent °f almost exactly
B, layer of blaod; C, collimator for rendering rays one-third pi I percent.,
parallel ; D, prism ; E, telescope. an<3 there is alsoa little
sulphur. Haemoglobin
is made up of a protein element which contains all the sulphur and a
pigment which contains all the iron, the protein constituting by far
the larger portion of the gigantic molecule, whose weight has been
estimated at more than 16,000 times that of a molecule of hydrogen.
Since its percentage composition is still undetermined with absolute
precision, it is impossible to give an empirical formula that is more
than approximately correct. For dog's haemoglobin Jaquet gives
C-58Hi203Ni95S3FeO2i8- which would make the molecular weight 16,669.
Direct determinations of the molecular weight gave 15,115 for
oxyhsemoglobin of the horse, and 16,321 for that of the ox (Hiifner and
Gansser). Whilethese numbers need not be taken as more than a rough
approximation, they at least show that the haemoglobin molecule is an
exceedingly large one.
The most remarkable property of haemoglobin is its power of
combining loosely with oxygen when exposed to an atmosphere con-
taining it, and of again giving it up in the presence of oxidizable
substances or in an atmosphere in which the partial pressure of
oxygen (pp. 248-253) has been reduced below a certain limit. It
ChEMICAL COMPOSITION OF BLOOD
D E b F
i
640 630 620 610 600 SM 580 570 560 550 5W 5ti 5W\ 510 500 490
I 1 I I I I' i I i I I I II! ! I
lll(lllllllllllllll[llllllllllll[lllllllllllllllllljllll|lllllillllllllllll!lllllllllllllllMllllllllllllljlllill!l!!;:i!lllll!llllllllllllllHllllllllllllllll
Fig. 13. — Table of Spectra of Haemoglobin and its Derivatives (Ziemka and MiilJerj.
i, Oxyhosmoglobin ; 2, reduced haemoglobin 3, methasmoglobin ; 4, ac 'd haematia ;
5, alkaline haematin; 6, haemochromogen ; 7, acid hamatoporphyrin ; 8, alkaline
hajmatoporphyrin ; 9, carbon monoxide haemoglobin.
52 THE CIRCULATING LIQUIDS OF THE BODY
is this property that enables haemoglobin to perform the part of an
oxygen-carrier to the tissues, a function of the first importance,
which will be more minutely considered when we come to deal with
respiration.
The bright red colour of blood drawn from an artery or of venous
blood after free exposure to air is due to the fact that the haemo-
globin is in the oxidized state
— in the state of oxyhaemo-
globin, as it is called. The
amount of oxygen with which
haemoglobin combines to form
oxyhaemoglobin is such that
one atom of iron corresponds to
two atoms of oxygen. If the
formula for haemoglobin given
on p. 50 be represented by
the symbol Hb, a molecule of
oxyhaemoglobin would be re-
presented as Hb02. If the
oxygen is removed by means of
reducing agents, such as am-
monium sulphide, or by ex-
posure to the vacuum of an air-
pump, the colour darkens, the
blood-pigment being now in the
form of reduced haemoglobin.
In ordinary venous blood a
large proportion of the pigment
is in this condition, but there is
always oxyhaemoglobin present
as well. In asphyxia (p. 281),
however, nearly the whole of
the oxyhaemoglobin may dis-
appear.
Crystallization of H cemoglobin. — In the circulating blood the haemo-
globin is related in such a way to the stroma of the corpuscles that,
although the latter are suspended in a liquid readily capable of dissolv-
ing the pigment, it yet remains under ordinary circumstances strictly
within them. In a few invertebrates, however, it is normally in solution
in the circulating liquid. As a rare occurrence haemoglobin may form
crystals inside the corpuscles (p. 71). When it is in any way brought
into solution outside the body, it shows in many animals, but not in the
same degree in all, a tendency to crystallization ; and the ease with which
crystallization can be induced is in inverse proportion to the solubility
of the haemoglobin. Thus, it is far more difficult to obtain crystals of
haemoglobin from human blood than from the blood of the rat, guinea-
pig, or dog, whose blood-pigment is less soluble than that of man, and
for a like reason the oxyhaemoglobin of the bird, the rabbit, or the frog
crystallizes still less readily than that of human blood.
Fig. 14. — Oxyhaemoglobin Crystals (Frey).
a, b, from man ; c, from cat ; d, from guinea-
pig; e, from hamster; /, from squirrel.
CHEMICAL COMPOSITION OF BLOOD 53
As to the form of the crystals, in the vast majority of animals they
are rhombic prisms or needles, but in the guinea-pig they are sphenoids
belonging to the rhombic system, and in the squirrel six-sided plates of
tae hexagonal system (Fig. 14). Careful study of the crystallography of
haemoglobin from a large number of animals has established differences
and resemblances so constant and so clear-cut that they may be used for
the purposes of classification and for the identification of the source of
a specimen of blood (Reichert and Brown).
Reduced haemoglobin can also be caused to crystallize, though with
more difficulty than oxyhaemoglobin, since it is more soluble. Crystals
of reduced haemoglobin were first prepared from human blood by Hiifner,
who allowed it to putrefy in sealed tubes for several weeks.
When a solution of oxyhsemoglobin of moderate strength is ex-
amined with the spectroscope, two well-marked absorption bands
are seen, one a little to the right of Fraunhofer's line D, and the other
a little to the left of E. A third band exists in the extreme violet
between G and H. It cannot be detected with an ordinary spectro-
scope, but has been studied by the aid of a fluorescent eyepiece, by
projecting the spectrum on a fluorescent screen, and by photograph-
ing the spectrum. The addition of a reducing agent, such as
ammonium sulphide, causes the bands in the visible spectrum to
disappear, and they are replaced by a less sharply denned band, of
which the centre is about equidistant from D and E. This is the
characteristic band of reduced haemoglobin. The spectrum of
ordinary venous blood shows the bands of oxyhaemoglobin.
Carbonic oxide haemoglobin is a representative of a class of haemo-
globin compounds analogous to oxyhaemoglobin, in which the loosely-
combined oxygen has been replaced by other gases (carbon monoxide,
nitric oxide) in firmer union. Its spectrum shows two bands very like
those of oxyhaemoglobin, but a little nearer the violet end. Carbonic
oxide haemoglobin is formed in poisoning with coal-gas. Owing to the
great stability of the compound, the haemoglobin can no longer be
oxidized in the lungs, and death may take place from asphyxia. It
is, however, gradually broken up, and therefore artificial respiration
may be of use in such cases. Inhalation of oxygen and especially
transfusion of blood are also of great value.
Methcemoglobin is a derivative of oxyhaemoglobin which can be
formed from it in various ways — e.g., by the addition of ferricyanide of
potassium or nitrite of amyl (Gamgee), by electrolysis (in the neigh-
bourhood of the anode), or by the action of the oxidizing ferment
' echidnase ' in the poison of the viper (Phisalix) . It very often appears
in an oxyhaemoglobin solution which is exposed to the air. It has been
found in the urine in cases of haemoglobinuria, in the fluid of ovarian
cysts, and in haematoceles. The strongest band in its spectrum is
in the red, between C and D, but nearer C, nearly in the same position
as the band of acid-haematin. Reducing agents, such as ammonium
sulphide, change methaemoglobin first into oxyhaemoglobin and then
into reduced haemoglobin. It has by some been regarded as a more
highly oxidized haemoglobin than oxyhsemoglobin. Rebutting evidence
has, however, been offered to the effect that the same quantity of
oxygen is required to saturate both pigments, and this evidence appears
to be sound. The difference lies rather in the manner in which the
oxygen is united to the haemoglobin in the methaemoglobin molecule
than in the quantity of oxygen which it contains. For methaemo-
54
THE CIRCULATING LIQUIDS OF THE BODY
globin, unlike oxy haemoglobin, parts with no oxygen to the vacuum,
while, on the other hand, in the presence of reducing agents it yields up its
oxygen even more readily than oxyhaemoglobin does (Haldahe) (p. 248).
By the action of acids or alkalies oxyhaemoglobin is split into a pig-
ment, haematin, and a protein, globin, belonging to the histon group.
It is easily precipitated from solution by ammonia. On hydrolysis, it
if*
\l'/''-~.
• — -.^ —
I; 1
/
..-•""
I
Xxj>
•*•<;
D
o
E
Carbonic ox-ideftb.
Hafmcch romotfen
Hae-matcfiorfihyrm (acidj\
ft ctd Haematin I ^«fc
Alkaline Haematm r,hlef.
Reduced hb, \band
rig 15. — Diagram to show the Chief Characteristics by which Haemoglobin and
some of its Derivatives may be recognized Spectroscopically. The position of
the middle of each band is indicated roughly by a vertical line-
yields a large amount of histidin, to which its basic properties are chiefly
due From 100 grammes of oxyhaemoglobin about 4 grammes of hae-
matin are obtained. As to the pigment moiety, when haemoglobin is
acted on by acids in the absence of oxygen, h cemochromogen is first
formed, which then gradually loses its iron and is changed into haemato-
porphyrin. If oxy-
Liv»e 29-3
TTueclts 29'2
s,heirTv lungs Zi'7
Bones 8'Z
genital organs 6'3
^Ain 27
Kidneys 1'6
Nerve centres 7'2
SpJeen "i-
Fig. 16. — Diagram to illustrate the Distribution of the
Blood in the Various Organs of a Rabbit (after Ranke's
Measurements). The numbers are percentages of the
total blood.
gen be present, hae-
matin is the final
product. Haematin
may be considered
as the compound
which haemochro-
mogen forms with
oxygen. By the
action of alkalies re-
duced haemoglobin
yields haemochro-
mogen, which is stable in alkaline solution, and gives a beautiful
spectrum with two bands, bearing some resemblance to those of oxy-
hsemoglobin, but placed nearer the violet end. The band next the red
end is much sharper than the other (p. 76). Haemochromogen binds
exactly the same amount of oxygen as the haemoglobin from which it is
derived, and it is due to the haemochromogen in its molecule that the
blood-pigment fulfils its function of taking up and transporting oxygen.
Hesmatin (C32H 320^4. FeOH), the most frequent result of the splitting
up of haemoglobin, is generally obtained as an amorphous substance
with a bluish-black colour and a metallic lustre, insoluble in water,
but soluble in dilute alkalies and acids, or in alcohol containing them.
In addition to the iron of the haemoglobin, haematin contains the four
chief elements of proteins — carbon, hydrogen, nitrogen, and oxgyen
(Practical Exercises, p. 75).
H (ematoporphyrin (C33H38O6N4), or iron-free haematin, may be ob-
tained from blood or haemoglobin by the action of strong sulphuric
acid, from haematin or haemin by the action of hydrobromic acid. It
55
is distinguished from these pigments by the fact that it contains no
iron. When strong sulphuric acid is allowed to act on blood or haemo-
globin solution, haematoporphyrin is also produced, as may be easily
shown by the spectroscope. Its spectrum in acid solution shows two
bands, one just to the left of D, the other about midway between D
and E. Like oxyhsemoglobin, reduced haemoglobin, carbonic oxide
haemoglobin, methaemoglobin, and other derivatives of haemoglobin,
it also has a band in the ultra-violet.
Hamin (C32H 330^4. Fed) is readily obtained from haematin and
also from haemoglobin by heating with dilute hydrochloric acid, and also
directly from blood, as described in the Practical Exercises, p. 78. It
crystallizes in the form of small rhombic plates, of a brownish or
brownish-black colour (Fig. 24, p. 78). They are insoluble in water,
but readily soluble in dilute alkalies (Practical Exercises, p. 79).
Chemistry of the White Blood-Corpuscles. — The composition of pus-
cells and the leucocytes of lymphatic glands has alone been investigated.
The chief constituents of the latter are a globulin coagulating by heat
at 48° to 50° C. ; a nucleo-protein coagulating in 5 per cent, magnesium
sulphate solution at 75° C., and causing coagulation of the blood on
injection into the veins of rabbits; an albumin coagulating at 73° C. ;
and a ferment with powers like the pepsin of the gastric juice. In pus-
cells glycogen has been found, and it can be demonstrated micro-
chemically in the leucocytes of blood by the iodine reaction in various
conditions. Fats, cholesterol, and lecithin are also present, as well
as the so-called protagon. The ordinary inorganic constituents have
been demonstrated — namely, potassium, sodium, calcium, magnesium,
and iron, united with chlorine and phosphoric acid. The total solids
amount to n to 12 per cent.
SECTION IV. — QUANTITY AND DISTRIBUTION OF THE BLOOD.
The Quantity of Blood. — The quantity of blood in an animal is
most accurately determined by the method of Welcker. The animal
is bled from the carotid into a weighed flask. When blood has
ceased to flow the vessels are washed out with water or physiological
saline solution, and the last traces of blood are removed by chopping
up the body, after the intestinal contents have been cleared away,
and extracting it with water. The extract and washings are mixed
and weighed ; a given quantity of the mixture is placed in a hasma-
tinometer (a glass trough with parallel sides, e.g.), and a weighed
quantity of the unmixed blood diluted in a similar vessel till the tint
is the same in both. From the amount of dilution required, the
quantity of blood in the watery solution can be calculated. This is
added to the amount of unmixed blood directly determined. Since
haemorrhage is immediately followed by the entrance of liquid into
the bloodvessels from the lymph and tissue fluids, somewhat too ;
high a result will be obtained if the bleeding is at all prolonged. T t
is well, therefore, to take only a moderate amount of blood for din
estimation, and to compute the balance by the colorimetric method.
Many other methods have been devised on the principle of in-
jecting a known quantity of some substance into the circulating
blood, and then, after an interval has been allowed for mixture,
determining the change produced in a sample. Thus, the specific
56
gravity of a drop of blood having been measured, a certain quantity
of a solution of sodium chloride isotonic with the plasma may be
injected into a vein, and the specific gravity again determined. Or
the electrical resistance of a small sample of blood may be measured
before and after injection of a given quantity of isotonic salt solution.
The total mass of blood in a living man has been estimated by caus-
ing the person to inhale a mixture of carbon monoxide with oxygen
or air. The amount of carbon monoxide taken up is determined and
also, in a sample of blood taken from the finger the percentage
amount to which the haemoglobin has become saturated with carbon
monoxide. All that remains is to estimate the volume of carbon
monoxide (or, what is precisely the same thing, the volume of
oxygen) which 100 c.c. of blood will take up. This latter quantity
is called the percentage oxygen capacity. From these data the
total volume of the blood can be calculated. If the volume is
multiplied by the specific gravity the mass is obtained. Notwith-
standing the elegance of this method in principle, it is by no means
easy to obtain accurate results with it in practice. It unques-
tionably gives values for the total quantity of blood which are too
low. A better method is to inject into a vein a measured quantity
of a solution of a pigment (" vital red "), which is only slowly elimin-
ated and is not taken up to a sensible degree by the erythrocytes.
Samples of blood are drawn before and a short time after the injec-
tion and the plasma separated from each by the centrifuge. The
amount of pigment is then determined which must be added to the
first sample of plasma to make its tint the same as that of the
second. The total quantity of plasma can thus be calculated and
from it, by determining the relative proportion of corpuscles and
plasma in the blood, the total quantity of blood (Rowntree, etc.).
The quantity of blood in the body was greatly over-estimated by
the ancient physicians. Avicenna put it at 25 lb., and many loose
statements are on record of as much as 20 lb. being lost by a patient
without causing death. By Welcker's method the proportion of
blood to body-weight has been found to be in the dog i : 13, cat 1 : 14,
horse i : 15, frog i : 17, rabbit 1 : 19, fowl i : 20. In new-born
children the proportion was i : 19, in adult human beings (executed
criminals) i : 13. By the ' vital red ' method, the amount of
plasma was found to be one-twentieth and that of blood one-
eleventh to one-twelfth of the body-weight.
According to Dreyer, the blood volume is a function of the surface
of the body, so that the smaller and lighter animals in any given species
have a relatively greater blood volume than the larger and heavier
individuals. Accordingly, he considers that the practice of expressing
the volume of blood as a percentage of the body-weight should be
abandoned.
Fig. 16 (p. 54) illustrates the distribution of the blood in the
various organs of a rabbit. The liver and skeletal muscles each con-
tain rather more than one-fourth; the heart, lungs, and great vessels
LYMPH AND CHYLE 57
rather less than one- fourth ; and the rest of the body about one-fifth,
of the total blood. The kidney and spleen of the rabbit each contain
one-eighth of their own weight of blood, the liver between one-third
and one-fourth of its weight, the muscles only one-twentieth of their
weight.
SECTION V. — LYMPH AND CHYLE.
Lymph has been denned as blood without its red corpuscles
(Johannes Miiller); it resembles, in fact, a dilute blood-plasma,
containing leucocytes, some of which (lymphocytes) are common to
lymph and blood, others (coarsely granular basophile cells, present
only in small numbers) are absent from the blood. Lymph also
contains thrombocytes. The reason of this similarity appears when
it is recognized that the plasma of tissue-lymph (p. 460) is derived,
in large part at any rate, from the plasma of blood by a process of
physiological nitration (or secretion) through the walls of the
capillaries into the lymph-spaces that everywhere occupy the inter-
stices of areolar tissue, while the lymph of the lymphatic vessels is
in turn derived from the tissue fluid. But in addition to the con-
stituents of the plasma, lymph contains substances produced in the
metabolism of the tissues which pass into it directly. As collected
from one of the large lymphatic vessels of the limbs, or from the
thoracic duct of a fasting animal, lymph is a colourless or some-
times yellowish or slightly reddish liquid of alkaline reaction. Its
specific gravity is much less than that of the blood (1015 to 1030).
It coagulates spontaneously, but the clot is always less firm and less
bulky than that of blood. The plasma contains fibrinogen, from
which the fibrin of the clot is derived. Serum-albumin and serum-
globulin are present in much the same relative proportion as in blood,
although in smaller absolute amount. Neutral fats, urea, and sugar
are also found in small quantities. The inorganic salts are the same
as those of the blood-serum, and exist in about the same amount,
sodium preponderating among the bases, as it does in serum. The
following table shows the results of analyses of lymph from man and
the horse (Munk) :
Man.
Horse.
Water ....
95-0 per cent.
95-8 per cent.
[Fibrin
O-I }
O-I \
Other proteins -
4'i
2-9
Solids ] Fat -
I Extractives*
trace j- 5-0
o-3
trace V 4*2
O-I
[Salts - --.
0-5 )
i-i )
* The term ' extractives ' is somewhat loosely applied to organic substances
which exist in so small an amount, or have such indefinite chemical characters,
that they cannot be separately estimated, and are extracted together from the
residue by various solvents.
THE CIRCULATING LIQUIDS OF THE BODY
Chyle is merely the name given to the lymph coming from the
alimentary canal. The fat of the food is absorbed by the lym-
phatics, and during digestion the chyle is crowded with fine fatty
globules, which give it a milky appearance. There may also be in
chyle a few red blood-corpuscles, carried into the thoracic duct by a
back-flow from the veins into which it opens. Chyle clots like
ordinary lymph, the size of the clot varying according to the quantity
of fat present and enmeshed by the fibrin. Wounds of the thoracic
duct or of lymphatics opening into it are occasionally produced in
operations on the neck, and when these remain open chyle may be
readily collected. In samples obtained from a patient only a week
after the section of a branch of the duct during an operation for the
removal of tubercular glands, water constituted 928-90 parts in
1,000, total solids 71-10, inorganic solids 6-04, organic solids 65-06,
proteins 18-52, ether extract (fatty substances) 19-30 (Sollmann).
The following is the composition of a sample analyzed by Paton, and
obtained from a fistula of the thoracic duct in a man :
Water
Solids
Inorganic -
Organic -
Proteins
Fats -
Cholesterin
Lecithin
953-4
46-6
40-1
13-7
24-06
0-6
0-36
The quantity of chyle flowing from the fistula was estimated at as
much as 3 to 4 kilos per twenty-four hours, or nearly as much as the
whole of the blood. The flow has been calculated in various animals
at one- eighteenth to one-seventh of the body-weight in the twenty-
four hours. The quantity of lymph in the body is unknown, but it
must be very great — perhaps two or three times that of the blood.
Allied to tissue-lymph, but not identical with it, are the fluids
present in health in very small amount in such serous cavities as the
pericardium. The synovial fluid of the joints differs from lymph
especially in containing a small amount of a mucin-like substance.
The aqueous humour, and still more the cerebro-spinal fluid, are
characterized by a marked deficiency in solids, especially protein.
In the following table (from Spiro) the differences in the composition
of lymph and allied fluids from different parts of the body are illus-
trated.
Man : Ly:.".'r'h from
FistiM ia Thigh.
Horse : Lymph
from Xeck during
MasticStion.
Aqueous
Humour.
Cerebro-Spinal
Fluid.
Water - -
06-4 to 94-3
95
98-7
99 to 99-2
Salts - -
O-y ,, 0-87
o-75
0-5 to 0-8
Fat - -
Protein
O-O6 ,, O-22\
2-8 ,, 4-8 J
3'7
0-72
0-02 to 0-16
FUNCTIONS OF BLOOD AND LYMPH 59
The gases of the blood and lymph will be treated of in
Chapter IV., the formation of lymph in Chapter VIII., its circulation
in Chapter III.
SECTION VI. — THE FUNCTIONS OF BLOOD AND LYMPH.
We have already said that these liquids provide the tissues with
the materials they require, and carry away from them materials
which have served their turn and are done with. These materials
are gaseous, liquid, and solid. Oxygen is brought to the tissues in
the red corpuscles ; carbon dioxide is carried away from them partly
in the erythrocytes, but chiefly in the plasma of the blood and
lymph. The water and solids which the cells of the body take in
and give out are also, at one time or another, constituents of the
plasma. The heat produced in the tissues, too, is, to a large extent,
conducted into the blood and distributed by it throughout the body.
The leucocytes, as will be seen farther on, aid in some measure in the
absorption of certain of the food substances from the intestine. It is
not known whether, apart from this, they play any role in the normal
nutrition of other cells, although it is probable that they exercise an
influence on the plasma in which they live. But they have impor-
tant functions of another kind, to which it is necessary to refer briefly
here.
Phagocytosis. — Certain of the amoeboid cells of blood and lymph,
and the cells of the splenic pulp, are able to include or ' eat up '
foreign bodies with which they come in contact, in the same way as
the amoeba takes in its food. Such cells are called phagocytes ; and
it is to be remarked that this term neither comprises all leucocytes
nor excludes all other cells, for some fixed cells, such as those of the
endothelial lining of bloodvessels, are phagocytes in virtue of their
power of sending out protoplasmic processes, while the small,
relatively immobile lymphocyte is not a phagocyte.
Although it is not at present possible to assign a physiological
value to all the phenomena of phagocytosis, either as regards the
phagocytes themselves or as regards the organism of which they
form a part, there seems little doubt that under certain circumstances
the process is connected with the removal of structures which in the
course of development have become obsolete, or with the neutral-
ization or elimination of harmful substances introduced from with-
out, or formed by the activity of bacteria within the tissues. During
the metamorphosis of some larvae, groups of cilia and muscle-fibres
may be absorbed and eaten up by the leucocytes. In the metamor-
phosis of maggots, for example, the muscular fibres of the abdominal
wall, which are used in creeping, and are therefore not required in
the adult, degenerate, and are devoured by swarms of leucocytes
which migrate into them. In the human subject an example of
60 THE CIRCULATING LIQUIDS OF THE BODY
absorption of tissue by the aid of leucocytes is the removal of the
necrosed decidua reflexa, the fold of uterine mucous membrane
which envelops the ovum (Minot).
The behaviour of phagocytes towards pathogenic micro-organisms
is of even greater interest and importance. Metchnikoff laid the
foundation of our knowledge of this subject by his researches on
Daphnia, a small crustacean with transparent tissues, which can be
observed under the microscope. When this creature is fed with a
fungus, Monospora, the spores of the latter find their way into the
body-cavity. Here they are at once attacked by the leucocytes,
ingested, and destroyed. But after a time so many spores get
through that the leucocytes are unable to deal with them all ; some
of them develop into the first or ' conidium ' stage of the fungus ; the
conidia poison the leucocytes, instead of being destroyed by them,
and the animal generally dies. Occasionally, however, the leuco-
cytes are able to destroy all the spores, and the life of the Daphnia is
preserved. This battle, ending sometimes in victory, sometimes in
defeat, is believed by Metchnikoff to be typical of the struggle which
the phagocytes of higher animals and of man seem to engage in
when the germs of disease are introduced into the organism. He
supposes that the immunity to certain diseases possessed naturally
by some animals, and which may be conferred on others by vaccina-
tion with various protective substances, is, to a large extent, due to
the early and complete success of the phagocytes in the fight with
the bacteria; and that in rapidly- fatal diseases — such as chicken-
cholera in birds and rabbits, and anthrax in mice — the absence of
any effective phagocytosis is the factor which determines the result.
Others have laid stress on the action of protective substances sup-
posed to exist in the plasma itself. It is possible that such sub-
stances are manufactured by the leucocytes, and either given off by
them to the plasma by a process of ' excretion/ or liberated by their
complete solution.
The most recent investigations go to show that Metchnikoff's
phagocytic theory of immunity requires modification, at any rate in
the case of the higher animals and man, although the brilliant
biological observations on which it was originally built retain all
their value. He supposed that in the immunizing process the
leucocytes underwent certain changes, acquired, so to speak, a sort
of ' education ' that enabled them to cope with bacteria against
which they were previously powerless. It seems more probable
that in the presence of the substances that confer immunity, not only
the leucocytes, but other cells, are stimulated to produce bodies
which cut short the life, or inhibit the growth, of the bacteria
(alexins), or prepare them for being taken up by the phagocytes
(opsonins). It has been shown that bacteria which have been in
contact with serum containing the appropriate opsonins are taken
FUNCTIONS OF BLOOD AND LYMPH 61
up readily by leucocytes washed free from serum constituents by
physiological salt solution, whereas the washed leucocytes either do
not ingest bacteria which have not been acted on by serum, or take
them up in much smaller numbers. There is some evidence that in
certain bacterial infections — for example, chronic furunculosis, a
condition in which crops of boils continue to appear — the grip of the
bacteria on the body is perpetuated by a deficiency in the amount or
in the activity of opsonins capable of acting specifically upon the
micro-organisms in question. A numerical expression, which in
certain cases, perhaps, gives a measure of the patient's resistance to
the infection, has been worked out by Wright under the name
' opsonic index.' This index is the ratio between the average
number of bacteria taken up, under certain fixed conditions, by each
polymorphonuclear leucocyte in an emulsion made with the patient's
serum, and the average number taken up by similar leucocytes in an
emulsion made with normal serum. The significance of this index
and even the practicability of the methods used to ascertain it, are
still the subject of discussion.
Diapedesis. — The fact that leucocytes can pass out of the blood-
vessels into the tissues has a very important bearing on the subject
of phagocytosis. The phenomenon is called diapedesis, and is best
seen when a transparent part, such as the mesentery of the frog, is
irritated. The first effect of irritation is an increase in the flow of
blood through the affected region. If the irritation continues, or if
it was originally severe, the current soon begins to slacken, the
corpuscles stagnate in the vessels, and inflammatory stasis is pro-
duced. The leucocytes adhere in large numbers to the walls of the
capillaries, and particularly of the small veins, and then begin to pass
slowly through them by amoeboid movements, the passage taking
place at the junctions between, or it may be through the substance of,
the endothelial cells. Plasma is also poured out into the tissues,
the whole forming an inflammatory exudation. Even red blood-
corpuscles may pass out of the vessels in small numbers. The
exudation may be gradually reabsorbed, or destruction of tissue
may ensue, and a collection of pus be formed. The cells of pus are
emigrated leucocytes (Practical Exercises, Chap. III., p. 193).
Their emigration is connected with the defence of the organism
against the entrance of certain forms of bacteria at the seat of
injury, and with the repair of the injured tissue, but the nature of
the summons which gathers them there is not yet clearly under-
stood. It is probably some sort of chemical attraction (chemio-
taxis) between constituents of the bacteria or decomposition prod-
ucts of the injured tissue on the one hand, and constituents of the
leucocytes on the other.
As for the blood-plates, it will suffice to say by way of summary
that their important function in the sealing of wounded vessels (p. 46)
62 THE CIRCULATING LIQUIDS OF THE BODY
is the sole office which at present can be attributed to them. And
if it is permissible to consider the leucocytes as a patrol for the
defence of the tissues in general against invading micro-organisms, it
may perhaps not be too far-fetched an idea to look upon the blood-
plates as essentially a patrol in the interests of the anatomical
integrity of the vascular system itself. This does not exclude the
possibility that the clotting of extravasated plasma may furnish a
more favourable medium for the processes of repair in all injured
tissues.
PRACTICAL EXERCISES ON CHAPTER II.
N.B. — In the following exercises all experiments on animals which
would cause the slightest pain are to be done under complete ancesthesia.
1. Reaction of Blood. — (i) Put a drop of fresh dog's or ox blood on
a piece of glazed neutral litmus paper (the litmus paper can be glazed
by dipping it into a neutral solution of gelatin and allowing it to dry).
Wash the blood off in 10 to 30 seconds with distilled water. A bluish
stain will be left, showing that fresh blood is alkaline. (2) Repeat with
dog's or ox serum. It is not necessary to wash the serum off, as it
does not obscure the change of colour. (3) Repeat (i) with human
blood. With a clean suture-needle or a good-sized sewing-needle
which has been sterilized in the flame of a Bunsen burner, prick one of
the fingers behind the nail. Bandaging the finger with a handkerchief
from above downwards, so as to render its tip congested, will often
facilitate the getting of a good-sized drop, but for quantitative experi-
ments, like 2, 10, and 17 (4), this should not be done.
2. Specific Gravity of Blood — Hammer schlag's Method. — (i) Put a
mixture of chloroform and benzol of specific gravity i -060 into a small
glass cylinder. Put a drop of dog's or ox defibrinated blood into the
mixture by means of a small pipette. If the drop sinks add chloroform,
if it rises add benzol, till it just remains suspended when the liquid has
been well stirred. Then with a small hydrometer measure the specific
gravity of the mixture, which is now equal to that of the blood. Filter
the liquid to free it from blood, and put it back into the stock-bottle.
(2) Obtain a drop of human blood as in i, and repeat the measurement
of the specific gravity.
3. Coagulation of Blood.* — (i) Take three tumblers or beakers, label
them a, £, and y, and measure into each 100 c.c. of water. Mark the
level of the water by strips of gummed paper, and pour it out. (If a
sufficient number of graduated cylinders is available, they may of
course be used, and this measurement avoided.) Into a put 25 c.c
of a saturated solution of magnesium sulphate, into ft 25 c.c. of a i per
cent, solution of potassium or ammonium oxalate in 0-9 per cent,
solution of sodium chloride, and into y 25 c.c. of a 1-2 per cent, solution
of sodium fluoride in 0-9 per cent, salt solution If the dog provided
is a large one, these quantities may be all doubled ; for a small dog they
may be all halved.
* This experiment requires two laboratory periods, the various blood mix-
tures being obtained during the first and worked up during the second.
(2) Insert a cannula into the central end of the carotid artery of a
dog anaesthetized with morphine* and ether, or A.C.E. mixture. f
To put a Cannula into an Artery. — Select a glass cannula of suitable
size, feel for the artery, make an incision in its course through the
skin, then isolate about an inch of it with forceps or a blunt needle,
carefully clearing away the fascia or connective tissue. Next pass a
small pair of forceps under the artery, and draw two ligatures
through below it. If the cannula is to be inserted into the central
end of the artery, tie the ligature which is farthest from the heart,
and cut one end short. Then between the heart and the other
ligature compress the artery with a small clamp (often spoken of as
' bulldog ' forceps). Now lift the artery by the distal ligature, make a
transverse slit in it with a pair of fine scissors, insert the cannula, and
tie the ligature over its neck. Cut the ends of the ligature short. If
the cannula is to be put into the distal end of the artery, both ligatures
must be between the clamp and the heart, and the bulldog must be put
on before the first ligature (the one nearest the heart) is tied, so that
the piece of bloodvessel between it and the ligature may be full of
blood, as this facilitates the opening of the artery.
(3) Run into a, /3, and y enough blood to fill them to the mark.
Shake the vessels, or stir up once or twice with a glass rod, to mix the
blood and solution.
(4) Take a small thin copper or brass vessel, and place it in a freezing
mixture of ice and salt. Run into it some of the blood from the artery.
It soon freezes to a hard mass. Now take the vessel out of the
freezing mixture and allow the blood to thaw. It will be seen that it
remains liquid for a short time and then clots.
(5) Run some of the blood into a porcelain capsule, stirring it
vigorously with a glass rod. The fibrin collects on the rod; the blood
is defibrinated and will no longer clot.
(6) Now let some blood run into a small beaker or jar. Notice that
the blood begins to clot in a few minutes, and that soon the vessel
can be tilted without spilling it. Note the time required for clotting
to occur. Set the coagulated blood aside, and observe next day that
clear yellow serum has separated from the clot.
(7) Weigh out a quantity of Witte's ' peptone ' equivalent to
0-5 gramme for every kilo of body-weight of the dog. Dissolve the
peptone in about twenty times its weight of 0-9 per cent, salt solution.
Put a cannula into the central end of a crural vein (p. 212). Fill the
cannula with the peptone solution and connect it with a burette. Put
15 drops of the peptone solution into a test-tube labelled ' Peptone A.'
Put the rest into the burette, and see that the connecting tube is filled
with the solution and free from air. Run into the test-tube about
5 c.c. of blood from the cannula in the carotid. Now let the peptone
solution flow from the burette into the vein. Feel the pulse over the
heart as the solution is running in. If the heart becomes very weak,
stop the injection ; otherwise the animal may die from the great lower-
ing of blood-pressure (p. 214). As soon as the injection is finished,
draw off a sample of 5 c.c. of blood into a test-tube labelled ' Pep-
tone B,' and let it stand. In ten minutes collect five further samples
of 5 c.c. (' Peptone C, D, E, F, G '), and a large one, H; in half an hour
* One to 2 centigrammes of morphine hydrochlorate per kilogramme of
body-weight should be injected subcutaneously about half an hour before
the operation. Ten c.c. of a 2 per cent, solution is sufficient for a dog of
good size. Note that diarrhoea and salivation .are caused by such a dose.
For directions for fastening the dog on the holder, see footnote on p. 199.
f A mixture of i part of alcohol, 2 of ether, and 3 of chloroform.
64
THE CIRCULATING LIQUIDS OF THE BODY
another set of five small samples, and at as long an interval as possible
thereafter five more. Now letting the dog bleed to death, observe that
the flow of blood is temporarily increased by pressure on -the abdominal
walls, which squeezes it towards the heart, by passive mavements of
the hind-legs, and also during the convulsions of asphyxia, which soon
appear. Add to the peptone blood D '5 c.c. of serum, to E a little
sodium chloride extract of liver, to F a little extract of muscle, and to
G 15 drops of a 2 per cent, solution of calcium chloride, and put C, D,
E, F, and G into a water-bath at 40° C. Treat the other sets of small
samples in the same way. Note
how long each specimen takes to
clot, and report your results.*
(8) Observe that the blood in a,
8, and y has not coagulated. Label
four test-tubes ' Oxalate A, B, C,
D,' and put into each about 5 c.c.
of the oxalated blood. Add to A
and B 5 or 6 drops of a 2 per cent,
solution of calcium chloride, to C 12
drops, and to D as much as there
is of the blood. Leave A at the
ordinary temperature, put the other
test-tubes in a water-bath at 40° C.,
and note when clotting occurs.
(9) To 10 c.c. of the fluoride blood
add a little more CaCl2 than is re-
quired to combine with the excess
of fluoride present . Label four test-
tubes ' Fluoride A, B, C, D,' and
into each put about 2 c.c. of this
' recalcified ' fluoride blood. To B
add i c.c. liver extract, to C I c.c.
muscle extract, and to D 4 c.c.
water. Label two more test-tubes
' Fluoride E and F.' Into each put
2 c.c. of the fluoride blood without
CaCl2. Add also to E i c.c. liver
extract and to F i c.c. serum. Put
all the tubes in a bath at about
40° C., and observe in which and in
what time coagulation takes place.
(10) By means of a centrifuge
(Fig. 17) separate the plasma from
the corpuscles in a, ft, and y, and
also from the peptone blood.
With the oxalate plasma from /3,
and the fluoride plasma from y, repeat the observations in (8) and
(9), using smaller quantities of the plasma, if necessary, in small test-
tubes. With the plasma from a perform the following experiments:
Put a small quantity of the plasma (i c.c.) into four test-tubes, labelling
* Sometimes the injection of peptone hastens coagulation instead of hinder-
ing it. It has been asserted that this is only the case when small doses are
used (less than 0*02 gramme per kilo of bod y- weight) . But in 2 dogs out of
ii a dose of 0^5 gramme per kilo has been seen to hasten coagulation, and in
i out of 12 to leave it unaffected; in the other 9 coagulation was markedly
retarded
Fig. 17. — Centrifuge (Jung), The four
cylinders shown at the top of the
figure are so swung that they become
horizontal as soon as speed is up.
PRACTICAL EXERCISES 65
them ' Magnesium Sulphate A, B, C, D.' Dilute B with four times, C
with eight times, and D with twenty times as much distilled water as
was taken of the plasma. Observe in which, if any, coagulation occurs,
and the time of its occurrence, and report the result.
(n) With peptone plasma from H and from the peptone blood
obtained later repeat the experiments done in (7). In addition dilute
i c.c. of the plasma with three volumes of water and i c.c. of it with
ten volumes of water, and put in the bath at 40° C. Observe whether
clotting occurs.
Instead of dog's blood, the blood of an ox or pig may be obtained at
the slaughter-house.
4. Preparation of Fibrin-Ferment. — Precipitate blood- serum with
ten times its volume of alcohol. Let it stand for several weeks, then
extract the precipitate with water. The water dissolves out the fibrin-
ferment, but not the coagulated serum proteins.
3. Preparation of Tissue Extracts containing Thrombokinase. — In a
dog or rabbit killed by bleeding insert a cannula into the lower end of
the thoracic aorta. Fill the cannula with 0-9 per cent, salt solution,
and connect it with a bottle also containing salt solution. Wash
put the vessels of the lower portion of the body, making an opening
in the inferior vena cava above the diaphragm to allow the liquid
to escape. For the sake of cleanliness, a cannula armed with a
piece of rubber tubing should be inserted for this purpose into the
inferior vena cava. Continue the injection till the liquid issues colour-
less. Then remove portions of liver and muscle. Mince each separately.
Rub up with sand in a mortar. Add 0-9 per cent, sodium chloride
solution and rub up again. Put into bottles and keep in the ice-chest.
For use take off some of the liquid from the top with a pipette, or strain
through cheese-cloth.
6. Serum. — Test the reaction, and determine, both by the hydrom-
eter and the pycnometer, or specific gravity bottle, the specific
gravity of the serum provided, or of the serum obtained in experi-
ment 3.
Serum Proteins. — (i) Saturate serum with magnesium sulphate
crystals at 30° C. The serum-globulin is precipitated. Filter off.
Wash the precipitate on the filter with a saturated solution of mag-
nesium sulphate. Dissolve the precipitate by the addition of a little
distilled water, and perform the following tests for globulins : (a) Satu-
rate with magnesium sulphate. A precipitate is obtained, (b) Drop
into a large quantity of water, and a flocculent precipitate falls down.
(c) Heat. Coagulation occurs. Determine the temperature of coagu-
lation (p. 9).
(2) To a portion of the filtrate from (i) add sodium sulphate to
saturation. The serum-albumin is precipitated. (Neither magnesium
sulphate nor sodium sulphate precipitates serum-albumin alone, but
the double salt sodio-magnesium sulphate precipitates it, and this is
formed when sodium sulphate is added to magnesium sulphate.)
(3) Dilute another portion of the filtrate from (i) with its own bulk
of water. Very slightly acidulate with dilute acetic acid, and de-
termine the temperature of heat coagulation.
(4) Precipitate the serum-globulin from another portion of serum by
adding to it an equal volume of saturated solution of ammonium
sulphate. Filter. Precipitate the serum-albumin from the filtrate by
saturating with ammonium sulphate crystals.
(5) Dilute serum with ten to twenty times its volume of distilled
water, and pass through it a stream of carbon dioxide. The serum-
globulin is partially precipitated.
5
66 THE CIRCULATING LIQUIDS OF THE BODY
(6) Acidulate some serum with dilute acetic acid and boil. Filtei
off the coagulum, and to the filtrate add silver nitrate. A non-protein
precipitate insoluble in nitric acid, but soluble in ammonia, indicates
the presence of chlorides.
7. Action of Serum on Artery Rings. — Cut a number of rings about
i£ millimetres wide from a fresh carotid artery of the sheep, obtained
from the slaughter-house. Keep the rings in a dish in Ringer's solu-
tion.* They should be as nearly as possible of uniform width. A small
cylindrical glass vessel is supported on a stand in such a way that it
can be easily lowered into a bath of water kept at a temperature of
about 39° to 40°. A stock of Ringer's solution is kept in a beaker
or bottle immersed in the bath. A ring of the artery is put into the
small cylinder, where it is held between two aluminium hooks, one
fastened to the bottom of the cylinder, the other (the upper one) con-
nected with the short arm of a lever, the long arm of which is arranged
to write on a slowly revolving drum. A time-trace, say in half-
minutes, is recorded below. The small cylinder is now filled with
warm Ringer's solution and lowered into the bath. Oxygen is bubbled
through the solution by means of a side-tube near the bottom of the
cylindrical vessel. The artery ring is now stretched for five minutes
by a weight of 10 grammes attached to the long arm of the lever at the
same distance from the axis as that at which the ring is attached.
After the stretching period the weight is removed, and a little tune
allowed to elapse tUl the writing-point traces a horizontal line on the
drum. Then a bent pipette is filled with serum already heated to bath
temperature in a vessel immersed in the bath. The pipette is intro-
duced into the small cylinder so that its point is at the bottom, without
disturbing the ring, and the serum is allowed to run in till the Ringer
solution is displaced. The ring shortens under the influence of the con-
strictor substance in the serum, and the tracing is continued till the
shortening has reached its maximum and the trace is again horizontal
(Fig. 3, p. 46).
Various dilutions of the serum are now made with Ringer's solution,
and the greatest dilution in which the serum will still cause a percep-
tible constriction of the rings is determined. This affords a measure
of comparison with other sera of the strength of the constrictor action.
For each dilution of serum a separate ring must be used. It must be
remembered that comparisons of this kind can only be made with
arteries of the same sensitiveness, and different arteries vary much in
this regard.
8. Comparison of the Action of Serum and Adrenalin (Epinephrin) on
Artery Rings. — Tracings showing the effect of various dilutions of
adrenalin chloride on artery rings may now be taken for comparison
with the serum effects. The adrenalin dilutions should be made just
before use, as adrenalin is rapidly oxidized. Or a separate experiment
on the action of adrenalin may be made under ' Circulation,' as on
p. 216.
9. Comparison of the Action of Serum and Plasma on Artery Rings. —
Citrate plasma is obtained as follows: A cannula and attached rubber
tube are boiled, oiled inside with fresh olive-oil, and filled with a citrate
* This is the name given to a solution containing the most important of
the inorganic constituents of blood -serum in approximately the normal pro-
portions. The various ' Ringer's solutions ' used by different workers have
varied slightly. That recommended by Locke (for perfusion of the isolated
heart) contains NaCl, 0-9 per cent.; KC1, 0*042 per cent.; CaCl2, 0-024 per cent.;
NaHCO3, o-oi to 0-03 per cent.; with in addition o'i per cent, of dextrose,
which can be omitted for such experiments as 7.
PRACTICAL EXERCISES «7
solution made by dissolving sodium citrate in Ringer's solution to the
extent of- 2 per cent. The solution is prevented from escaping by a
clip on the tube. The cannula is inserted into the carotid of a dog,
the end of the rubber tube dipped below a quantity of citrate-
Ringer solution in a beaker, and a volume of blood equal to that of the
solution run in. Then the blood and solution are at once stirred gently,
but sufficiently to insure proper admixture.
Some blood is now run into another vessel, defibrinated, and
measured. An equal volume of the citrate-Ringer solution is added to
it while the mass of fibrin is still floating in the blodd. After mixing,
the fibrin is removed. Plasma is then separated by the centrifuge from
the first specimen of blood, and serum from the second, and comparison
experiments are made with each on artery rings. If the plasma has
been properly obtained, it will have little constrictor effect on the
rings in comparison with the serum. In making the comparison,
arteries which give a decided effect with serum should be employed.
The defibrinated blood and the unclotted citrate blood may also be
used for the comparison.
Fig. 18. — Thoma-Zeiss Haemocytometer. M , mouthpiece of tube G, by which
blood is sucked into S; E, bead for mixing; a, view of slide from above; b, in
section; c, squares in middle of B, as seen under microscope.
10. Enumeration of the Blood - Corpuscles. — Use the Thoma-Zeiss
apparatus (Fig. 18). (i) Suck a drop of ox or dog's blood up into
the capillary tube 5 to the mark i. Wipe off any blood which
may adhere to the end of the tube. Then fill it with 3 per
cent, sodium chloride to the mark 101. This represents a dilution of
100 times. Mix the blood and solution thoroughly, then blow put a
drop or two of the liquid to remove all the solution which remains in
the capillary tube. Now fill the shallow cell B with the blood mixture.
Put the cover-glass on, taking care that it does not float on the liquid,
but that the cell is exactly filled. Put the slide under the microscope
(say Leitz's oc. III., obj. 5), and count the number of red corpuscles
in not less than ten to twenty squares. Sixteen squares is a good
routine number. The greater the number of squares counted, the
nearer will be the approximation to the truth. Now take the average
number in a square. The depth of the cell is ^ mm., the area of each
square jj^ sq. mm. The volume of the column of liquid standing
upon a square is 1T^ cub. mm. One cub. mm- of the diluted blood
would therefore contain 4,000 times as many corpuscles as one square.
But the blood has been diluted 100 times, therefore i cub. mm. of the
6R THE CIRCULATING LIQUIDS OF THE BODY
undiluted blood would contain 400,000 times the number of corpuscles
in one square. Suppose the average for a square is found to be 13.
This would correspond to 5,200,000 corpuscles hi i cub. mm. of blood.
Compare your result with the true number supplied by the demon-
strator. (2) Prick the finger to obtain a drop of blood, and repeat
the crunt as in (i).*
To Count the White Corpuscles. — Add to i part of blood 9 parts of
i per cent, acetic acid, in order to lake the coloured corpuscles and
render it easy to see the leucocytes.
II. Relative Volume of Corpuscles and Plasma by Haematocrite. —
(i) For practice, fill the two graduated glass tubes with the defibrinated
blood of an animal. The rubber tube with mouthpiece supplied with
the apparatus is to be attached to the glass tube, and the blood sucked
up. Press the tip of the index-finger against the pointed end, and care-
fully remove the rubber tube . Place the tube in the haematocrite frame ,
blunt end outwards — that is, farthest from the axis of rotation — and
then slip the pointed end down into position against the spring. Instead
of the rubber tube, a special suction pipette for automatically filling
the graduated tubes may be employed (Daland) . Attach the haemato-
crite frame to the centrifuge, and rotate till the volume of sediment
Fig. 19.— Haematocrite. A, haematocrite attachment with graduated tubes; B, auto-
matic pipette for filling the tubes (Daland).
(corpuscles) ceases to diminish. The graduations are best read with a
hand lens. The leucocytes will be seen to form a thin whitish line
proximal to the column of red corpuscles.
(2) Prick the finger or the lobe of the ear, fill the tubes as in (i), and
centrifugalize. Everything must be done as rapidly as possible, so
that the blood may not clot till the separation of plasma and corpuscles
is completed. The centrifuge must rotate very rapidly (about 10,000
revolutions a minute) for two or three minutes. For clinical purposes
it is best to rotate the centrifuge always at the same speed for the
same length of time rather than to aim at reaching a constant length
of the column of corpuscles. In this way useful comparative results
can be obtained. It is well, to avoid the risk of accident, to rotate the
centrifuge under a guard.
12. Electrical Conductivity of Blood. — (i) Fill a small U-tube with
blood up to a mark. In each limb insert a platinum electrodef con-
* If the tube has not been properly filled, blow the blood out immediately.
On no account permit it to clot in the capillary tube.
t If the platinum electrodes are of good size and the resistance of the tube
of liquid considerable, it is not necessary to platinize them — i.e., to cover them
by electrolysis of a solution of platiuic chloride with a layer of platinum-black.
PRACTICAL EXERCISES 69
nected with a holder, which insures that the electrode shall always dip
to the same depth into the tube. Arrange the U-tube so that it is
immersed at least to the mark in water of constant temperature. Water
running freely from the cold-water tap into and out of a large vessel
will have a sufficiently constant temperature for the purpose. A ther-
mometer must be fixed in the water with its bulb in contact with the
U-tube. Connect the electrodes with a resistance -box in the Wheat-
stone's bridge arrangement (Fig. 231, p. 726), so that the U-tube
occupies the position of the unknown, resistance CD. Instead of the
battery F, connect the poles of the secondary of a small induction-coil,
arranged for an interrupted current, with A and C, and instead of the
galvanometer G insert a telephone. The resistances AB and AD will
be obtained by taking out two plugs from the appropriate part of the
resistance-box. Whether AB and AD should be equal (say, 10 : 10,
100 : 100, or 1,000 : 1,000 ohms) or unequal (say, 10 : 100, or
100 : 1,000, or 10 : 1,000 ohms) will depend upon the resistance of
the tube of liquid to be measured. Take out from the part of the box
corresponding to BC a plug representing a resistance something like
that which the tube of blood is expected to have. Close the primary
circuit of the induction-coil, and apply the telephone to the ear. A
buzzing sound will be heard, which will be louder the farther from the
true resistance of the tube the resistance taken out of the box is. Go
on altering the resistance in the box by taking out or putting in plugs
till the sound disappears, or is reduced to a minimum. The tempera-
ture of the water should now be read off. The resistance of the tube of
blood for this temperature can easily be calculated from the formula
on p. 726. It increases about 2 per cent, for each degree Centigrade of
diminution of temperature. The conductivity is the reciprocal of the
resistance. By determining once for all the resistance of the tube
when filled with a standard solution of a salt whose conductivity is
known, the specific conductivity of the blood can be expressed in
definite units, but this is not necessary for the purposes of the student.
Compare the resistances of defibrinated blood, serum, 0*9 per cent,
sodium chloride solution, and a sediment of blood-corpuscles separated
by centrifugalization.
(2) Instead of the resistance-box a wire mounted on a scale may be
used for the resistances AB, AD, the ends of the wire being connected
at B and D. A slider with an insulated handle moving along the
graduated wire is joined by a flexible wire with one pole of the secondary
coil, the other pole being connected at C. The resistance BC is consti-
tuted by a rheostat from which a fixed resistance can be taken out.
Instead of obtaining the minimum sound in the telephone by varying
the resistance BC in the box, the measurement is made by varying the
position of the slider; iu other words, by changing the ratio AB: AD.
(3) If no rheostat is available instructive comparative measurements
may still be made with the graduated wire by substituting for the
resistance BC a U-tube of another liquid.
If the tubes are of the same dimensions, and the liquids with which
they are filled are approximately at the same initial temperature, it
is not necessary to immerse them in water at constant temperature. It
is sufficient to place them side by side in the air. Perform the following
experiments in this way :
(a) Label the tubes A and B. Fill them both to the mark with
0-9 per cent. NaCl solution. Connect as in the figure, and move the
slider along the wire till the sound is a minimum. Probably the two
tubes are not exactly of the same dimensions, and therefore the slider
will not be exactly in the middle of the wire. Suppose it is at 49-0
TO THE CIRCULATING LIQUIDS OF THE BODY
the total length of the wire being 100. Then resistance of A : resistance
of B:: 49-0: 51-0, i.e., resistance of A = — resistance of B.
(6) Fill A with defibrinated blood, keeping B filled with NaCl solu-
tion, and repeat the measurement. The slider must now be moved
much farther away from the zero of the scale. Suppose the minimum
sound is obtained with the slider at 70*0. Then resistance of blood =
* x 2- resistance of the NaCl solution.
7 49
(c) Compare in the same way the resistance of serum with that of
the NaCl solution. It will be found much less than that of the blood.
(d) Centrifugalize some of the blood for as long as is convenient, and
compare the resistance of the blood from the top of the tubes and from
the bottom of the tubes with that of the NaCl solution. The resistance
of the blood from the bottom of the tubes will be found much greater
than that of the blood from the top.
13. Opacity of Blood. — Smear a little fresh blood on a glass slide, and
hold the slide above some printed matter. It will not be possible to
read it, because the light is reflected from the corpuscles in all directions,
and little of it passes through.
14. Laking of Blood by Chemical and Physical Agents. — (i) Put a
little fresh blood into three test-tubes, A, B, and C. Dilute A with an
equal volume, B with two volumes, and C with three volumes, of dis-
tilled water, and repeat experiment 9. The print can now be read
probably through a layer of A, but certainly through B and C, since
the haemoglobin is dissolved out of the corpuscles by the water and
goes into solution, the blood becoming transparent or laked. That the
difference is not due merely to dilution can be shown by putting an
equal quantity of blood in two test-tubes, and gradually diluting one
with distilled water and the other with a 0-9 per cent, solution of
sodium chloride, which does not dissolve out the haemoglobin. Print
can be read through the first with a smaller degree of dilution than
through the second. Examine the laked blood with the microscope
for the ' ghosts,' or shadows of the red corpuscles. The addition of a
drop or two of methylene blue will render them somewhat more distinct.
(2) Heat a little dog's or ox blood in a test-tube immersed in a water-
bath. Put a thermometer in the test-tube, taking care that there is
enough blood to cover the bulb. Keep the temperature about 60° C.
In a few minutes the blood becomes dark and laking occurs.
(3) (a) Put a little blood into each of four test-tubes. To one add a
little ether, to another a little chloroform, to the third dilute acetic
acid in 0-9 per cent. NaCl, and to the fourth a dilute solution of bile
salts (or of sodium taurocholate) in 0-9 per cent. NaCl solution. Laking
occurs in all.
(6) To 5 c.c. of blood add 0-5 c.c. of a 3 per cent, solution of saponin
in 0-9 per cent. NaCl solution, and put the mixture at 40° C. Laking
soon occurs.
(c) Using a 10 per cent, dilution of blood (blood to which nine volumes
of NaCl solution have been added) or a 5 per cent, suspension of washed
corpuscles in NaCl solution (i.e., a suspension of corpuscles which have
been washed free from serum by being repeatedly mixed with NaCl
solution and centrifugalized), determine the minimum dose of 0-3 per
cent, saponin solution which will just cause complete laking. Keep the
tubes at about 40° C., and observe them from time to time. Now add
to some of the 10 per cent, dilution or the 5 per cent, suspension of blood
an equal volume of serum from the same kind of blood, and repeat the
determination of the minimum dose of saponin necessary for laking.
PRACTICAL EXERCISES 71
It will be found that more is now required. The cholesterin in the
serum neutralizes the action of some of the saponin.
(4) (a) Put i c.c. of blood into each of two test-tubes. To one add
I c.c. of 2 per cent, aqueous solution of urea, and to the other 3 c.c.
Laldng will take place in the second, whether this has been the case in
the first or not.
(b) Repeat the experiment with a 2 per cent, solution of urea in
0-9 per cent. NaCl solution. Laking does not occur. This shows that
the urea in the first experiment did not act as a haemolytic agent.
Laking occurred because urea penetrates the corpuscles easily, and
therefore, although the freezing-point of the urea solution is not very
different from that of the NaCl solution, its actual osmotic pressure,
in relation to the envelopes of the corpuscles, is very much less, and the
laking is really water-laking.
(5) Put some blood into a flask or test-tube, cork up, and let it stand
till it begins to putrefy. It becomes laked. The same occurs when
the blood is collected aseptically in a sterile tube and sealed up, although
it takes a longer time for the laking to become complete.
(6) With blood containing nucleated corpuscles (necturus, frog or
chicken) diluted with isotonic salt solution, perform the following
experiments under the microscope :
(a) With a glass rod drawn to a fine point put a small drop of blood
on a slide, and near it a drop of distilled water. Carefully lower the
cover-slip and observe the interface with the microscope, first with the
low and then with the high power. Then mix and see complete laking.
Add a little methylene blue. Note that the nuclei still stain.
(6) Place a small drop of a 3 per cent, solution of saponin in isotonic
salt solution on a slide, and near it a small drop of blood. Observe as
in (a). Repeat with a 2 per cent, solution of sodium taurocholate in
salt solution. If necturus corpuscles, which are splendid objects for
such experiments on account of their great size, have been used,
intracorpuscular crystallization of the haemoglobin may be observed.
(c) Repeat (a) and (b) with mammalian blood. Note that the cor-
puscles swell before being laked by the saponin . If any of the corpuscles
are crenated, it may be seen that before being laked by the saponin
the crenations disappear, the corpuscles becoming round, while in the
taurocholate solution they may remain crenated till laking has occurred.
This indicates that the permeability of the envelopes is not affected in
the same way by the two laking agents.
15. Haemolysis and Agglutination by Foreign Serum. — (i) To a small
quantity of rabbit's blood add an equal volume of dog's serum. Mix
and let stand at 40° C. The colour of the blood is soon darker than
before, and it can be seen to be laked. Examine microscopically.
(2) Place a small drop of rabbit's blood and a somewhat larger drop
of the dog's serum on a slide, near, but not quite in contact with, each
other. Now put on a cover-slip, so that the drops just come together,
and examine at once with the microscope with a moderately high power.
Where the two drops mingle, the red corpuscles will be seen first to
become agglutinated into groups, and then to fade out, leaving only
their ' ghosts.' A few of the corpuscles which come into contact with
the, as yet, undiluted serum may be entirely dissolved.
(3) Heat some of the dog's serum to 60° C. for ten minutes, and
repeat (i) and (2). No laking will now be produced in the rabbit's
corpuscles, but agglutination may be observed as before.
(4) Repeat (i) and (2) with dog's bloo^ and rabbit's serum. The
blood will not be laked. although sometimes the dog's corpuscles may
become crenated. There will be no agglutination.
72 THE CIRCULATING LIQUIDS OF THE BODY
(5) With a 5 per cent, suspension of rabbit's washed corpuscles
perform the following experiments:*
Put into each of six small test-tubes i c.c. of the suspension. Label
the tubes A, A', B, B', C, C'.
(a) To A and A' add respectively o-i c.c. and 0-5 c.c. ox serum.
(b) To B and B' add respectively o-i c.c. and 0-5 c.c. dog's serum.
(c) To C and C' add respectively o-i c.c. and 0-5 c.c. of 0-9 per cent,
sodium chloride solution.
Put all the tubes in a bath at 40° C. Compare the amount of laking
and agglutination in the various tubes at intervals of two minutes or
less. Repeat (a), (b), and (c) with guinea-pig's washed corpuscles and
serum of ox and dog. Determine which of these sera has the strongest
haemolytic power.!
(6) Heat i c.c. of ox and dog's serum respectively to 56° C., keeping
it at that temperature, or not more than a couple of degrees above it,
for tenj minutes, and repeat experiment (5), labelling the tubes D, D',
E, E', F, F'. Save the rest of the heated sera for (8). There is no
laking in any of the tubes, but probably agglutination in D, D', and
E, E'. (The complement is destroyed, but not the intermediary body
or amboceptor, or the agglutinin — p. 28.)
(7) Put half of the contents of tubes D, D', E, E', into four separate
test-tubes, and add to each 0-2 c.c. of rabbit's serum. If there is laking
now it is because the rabbit's serum contains complement. Save the
balance of D, D', E and E' for (8).
(8) Allow 0-5 c.c. of ox serum to act at o° C. on the rabbit's washed
corpuscles contained in 5 c.c. of the 5 per cent, suspension after removal
of the sodium chloride solution. The ox serum and rabbit's corpuscles
are separately cooled to o° C. before being mixed, and the mixture is
then kept at o° C. for one hour. Centrifugalize the serum off rapidly.
Label it ' Serum S.' To 0-2 c.c. of the original 5 per cent, suspension
of rabbit's washed corpuscles add o;i c.c. of this serum (labelling the
tube G), and put at 40° C. with a control-tube containing the same
amount of suspension plus salt solution instead of serum. Add the
rest of the serum S, cooled to o° C., to the same cooled rabbit's cor-
puscles, and leave for a further period at o° C. Then Centrifugalize
rapidly, and to 0-2 c.c. of the original suspension of washed rabbit's
corpuscles add o-i c.c. of serum S (labelling the tube H), and put at
40° C. with a sodium chloride tube as control. There may be no
* The material obtained from one medium-sized dog, two rabbits, and one
guinea-pig is enough for fifty or sixty students, working together in sets of
two, to perform experiments (5) to (8). In order to obtain a serum more
strongly haemolytic for rabbit's corpuscles than normal dog's serum, a dog
may be ' immunized ' by previous injection of all the washed corpuscles
obtainable from a rabbit. The injection should be made under the skin or,
better, into the peritoneal cavity — of course, with aseptic precautions. It
should be repeated not less than twice, with an interval of ten days between
the successive injections, and the dog's blood should be drawn off about ten
days after the last injection.
f To determine the amount of laking at any given moment, drop the small
test-tubes into the metallic centrifuge cups after shaking them up, and centrif-
ugalize. A very short time is sufficient to separate a clear supernatant
liquid, from the tint of which the extent of the haemolysis can be deduced.
Before replacing the tubes in the thermostat, they should, of course, be shaken
up. Small test-tubes of about 8 mm. internal diameter and short enough to
go conveniently into the centrifuge cups are the most serviceable.
J For exact work a longer time is recommended. But for the student the
time is made as short as possible, and it is only in exceptional cases that ten
minutes is not enough.
PRACTICAL EXERCISES 73
laking in either G or H, or if there is laking it may be greater in G than
in H. The amboceptor has been removed from serum S by the rabbit's
corpuscles. Add o-i c.c. of this ' inactivated ' serum to the balance
of D, D', and E, E' (left from 6). Laking will occur because the serum S
contains complement, and the heated serum added in (6) to these tubes
contains amboceptor. Wash the rabbit's corpuscles which have been
treated with ox serum at o° C. with cooled sodium chloride solution.
Add to them some of serum S (that from the top of tube H will do if
no more is left), and put at 40° C. Laking will occur, showing that the
amboceptor was fixed by the rabbit's corpuscles at o° C. To a further
portion of the washed rabbit's corpuscles which were treated with ox
serum at o° C. add normal rabbit's serum, and put at 40° C. If laking
occurs it is because the rabbit's serum contains complement.
Dog's serum may be used instead of ox serum for experiment (8).
1 6. Osmotic Resistance of the Coloured Corpuscles. — Fill a burette
with a I per cent, solution of sodium chloride and another with dis-
tilled water. Take a series of ten test-tubes and run into the first
6 c.c. of the NaCl solution, into the second 5-8 c.c., into the third
5-6 c.c., and so on, always making a difference of 0-2 c.c. between
successive test-tubes. From the other burette run in enough distilled
water to make up 10 c.c. of solution in each tube — that is, 4 c.c. of dis-
tilled water for the first tube, 4-2 c.c. for the second, and so on. Shake
up. The tubes now contain a series of solutions of salt differing in
strength by 0-02 per cent, in successive tubes, the strongest being 0-6
per cent., and the weakest 0-42 per cent. Number the tubes i to 10,
beginning with the strongest solution. Put into each tube one drop of
perfectly fresh blood. Shake moderately so as to mix the blood and
salt solution, and allow the tubes to stand for ten to thirty minutes.
Observe the colour of the clear liquid above the sediment of corpuscles.
Determine in which tube the first tinge of haemoglobin appears. The
next higher concentration of the salt solution is that in which all the
corpuscles are just able to retain their haemoglobin, and is a measure of
the minimum osmotic resistance of the corpuscles, or the resistance
of the weakest corpuscles. Repeat with blood which has stood at room
temperature for twelve to twenty -four hours. For clinical purposes
tubes, each containing 5 c.c. of salt solution, may be used. A single
drop of blood can then be distributed between the tubes with a fine
pipette or a glass rod, beginning with the most concentrated solution,
and passing down to the less concentrated. The blood must be dis-
tributed rapidly before coagulation occurs. Only such concentrations
of the salt solution as are known to correspond to the possible variations
of the osmotic resistance for any particular disease or for any particular
variety of blood need be employed.
17. Blood-Pigment — (i) Preparation of Haemoglobin Crystals. — (a)
To a little dog's blood in a narrow test-tube add its own volume or
twice its volume of chloroform. Invert the tube ten or twelve times
so as to allow the chloroform to act on the blood, but avoid violent
shaking. When the tube is now allowed to stand for a few minutes
the laked blood all rises to the top. Remove a little of the layer of
blood without taking with it any of the chloroform layer, and examine
the oxyhaemoglobin crystals with the microscope. They form long
rhombic prisms and needles (Fig. 14, p. 52).
(b) Add a little crude saponin to dog's blood in a test-tube. Shake
up well, and allow it to stand till the colour becomes dark. Then shake
vigorously, and a mass of haemoglobin crystals will be formed.
(c) Put a small drop of guinea-pig's blood on a slide. Mix with a
74
drop of Canada balsam and cover. Tetrahedral crystals of oxy-
hsemoglobin will form after a time. The slide may be kept.
(2) Spectroscopic Examination of Haemoglobin and its Derivatives.
— (a) With a small, direct-vision spectroscope look at a bright part of
the sky or a white cloud. Focus by pulling out or pushing in the eye-
piece until the numerous fine dark lines (Fraunhofer's lines), running
vertically across the spectrum, are seen. Narrow the slit by moving
the milled edge till the lines are as sharp as they can be made. Note
especially the line D in the orange, the lines E and 6 in the green,
and F in the blue. Always hold the spectroscope so that the red is
at the left of the field. Now dip an iron or platinum wire with a
loop on the end of it into water, and then into some common salt or
sodium carbonate, and fasten or hold it in the flame of a fishtail burner.
On examining the flame with the spectroscope, a bright yellow line
will be seen occupying the position of the dark line D in the solar
spectrum. This is a convenient line of reference in the spectrum, and
in studying the spectra of haemoglobin and its derivatives, the position
of the absorption bands with regard to the D line should always be
noted. The dark lines in the solar spectrum are due to the absorption
of light of a definite range of wave-lengths by metals in a state of vapour
in the sun's atmosphere, and of course no dark lines are seen in the
spectrum of a gas-flame. Put some defibrinated blood into a test-tube.
Fig. 20. — Direct Vision Spectroscope ot Simple Type. A , slot in which a pin on the
eyepiece C slides in focussing the spectrum; B, milled head, by the rotation
of which the slit is narrowed or widened.
Fasten it vertically in a clamp in front of the flame and examine it
with the spectroscope, holding the latter in one hand with the slit close
to the test-tube, and focussing the eyepiece with the other. Or arrange
the spectroscope, test-tube and gas-flame on a stand as in Fig. 21.
Nothing can be seen till the blood is diluted. Pour a little of the blood
into another test-tube, and go on diluting till, on focussing, two bands of
oxyhesmoglobin are seen in the position indicated in Fig. 13, p. 51 . Draw
the spectrum; then dilute still more, and observe which of the bands
first disappears. Now put 5 c.c. of the blood into another test-tube,
and dilute it with four times its volume of water. Take 5 c.c. of this
dilution, and again add four times as much water, and so on till the
solution is only faintly coloured. Note with what degree of dilution
the bands disappear. Then examine each of the solutions with the
spectroscope and draw its spectrum.
(b) Make a solution of blood which shows the oxyhaemoglobin bands
sharply. Add some ammonium sulphide solution to reduce the oxy-
haemoglobin. Heat gently to about body temperature. A single,
ill-defined band now appears, occupying a position midway between
the oxyhEemoglobin bands, and the latter disappear. This is the
band of reduced hemoglobin (Fig. 13).
(c) Carbonic Oxide Hemoglobin. — Pass coal-gas through blood for
PRACTICAL EXERCISES
75
a considerable time. Examine some of the blood (after dilution)
with the spectroscope. Two bands, almost in the position of the
oxyhaemoglobin bands, are seen; but no change is caused by the
addition of ammonium sulphide, since carbonic oxide haemoglobin is
a more stable compound than oxyhaemoglobin.
(d) Methcemoglobin. — Put some blood into a test-tube, add a few
drops of a solution of ferricyanide of potassium, and heat gently. On
diluting a well-marked band will be seen in the red. On addition of
ammonium sulphide this band disappears; the oxyhaemoglobin bands
are seen for a moment, and then give place to the band of reduced
haemoglobin (Fig. 13, p. 51).
(e) Acid Hcematin. — To a little diluted blood add strong acetic acid
and heat gently. The colour becomes brownish. The spectrum
shows a band in the red between C and D, not far from the position
of the band of methaemoglobin. The addition of a drop or two of
ammonium sulphide causes no change in the spectrum, and this is a
means of distinguishing acid haematin from methaemoglobin. If more
ammonium sulphide be added,
haematin will be precipitated
when the acid solution has been
rendered neutral, and a further
addition of ammonium sulphide
or sodium hydroxide will cause
the haematin to be again dis-
solved, a solution of alkaline
haematin being formed. This A
in its turn may be reduced by
an excess of ammonium sul-
phide, and the spectrum of
Jest' tube
haemochromogen may be ob-
tained (Fig. 13, p. 51).
Since the watery solution
of acid haematin obtained as
above is usually somewhat tur-
bid, a solution in acid ether is
sometimes employed for spec-
troscopic examination. Add to
a little undiluted defibrinated
blood about half its volume of
glacial acetic acid, and then not
less than an equal volume of
Spectroscope
Solution.
0
Fig. 21. — Spectroscopic Examination of
Blood-Pigment.
ether. Mix well, pour off the ethereal extract and examine it with the
spectroscope, diluting, if necessary, with ether and glacial acetic acid.
It shows a strong band in the red somewhat farther from the D line
than the methasmoglobin band. On dilution, three additional fainter
bands may be seen.
(/) Alkaline Hcematin. — To diluted blood add strong acetic acid and
warm gently for a few minutes. Then, when the spectroscopic ex-
amination of a sample shows that acid haematin has been formed,
neutralize with sodium hydroxide. A brownish precipitate of haematin
is thrown down, which dissolves in an excess of sodium hydroxide,
giving a solution of alkaline haematin (or alkali haematin).
Or add sodium hydroxide to blood directly, and warm for a couple of
minutes after the colour has changed decidedly to brownish-black.
The spectrum of alkaline haematin is a broad but ill-defined band just
overlapping the D line, and situated chiefly to the red side of it (Fig. 13).
The solution should be shaken up with air before being examined, as
76 THE CIRCULATING LIQUIDS OF THE BODY
some of the alkali haematin is changed into haemochroraogen by re-
ducing substances formed by the action of the alkali on the blood.
(g) Hcemochromogen. — To a solution of alkaline haematin add a drop
or two of ammonium sulphide. The band near D disappears, and two
bands make their appearance in the green (Fig. 13, p. 51).
(A) Hcsmatoporphyrin. — Put some strong sulphuric acid into a test-
tube. Add a few drops of blood, agitate the test-tube till the blood
dissolves, and examine the purple liquid, diluting it, if necessary,
with sulphuric acid. Its spectrum shows two well-marked bands, one
just to the left of D, and the other midway between D and E (Fig. 13).
(3) Guaiacum Test for Blood.-^A test for blood — much used in
hospitals, and, indeed, a delicate one, but quite untrustworthy unless
certain precautions be taken — is the guaiacum test. A drop of freshly-
prepared tincture of guaiacum is added to the liquid to be tested, and
then peroxide of hydrogen. If blood be present, the guaiacum strikes
a blue or greenish-blue colour. The decomposition of the peroxide
by the blood is due mainly to the haemoglobin of the corpuscles. Any
derivative of haemoglobin which still con tarns the iron will act, and
boiling does not abolish this power. On the other hand, oxydases or
oxidizing ferments present, not only in the formed elements of blood,
but elsewhere, e.g., in fresh vegetable protoplasm, milk, seminal fluid,
and pus, will cause the same colour (p. 271), but not if they have been
previously boiled.* The test has been considered chiefly of value as
a negative test. When the blue colour is not obtained, we have good
evidence that blood is absent. But, according to Buckmaster, if the
precaution of first boiling the liquid suspected to contain blood be
adopted, it is also a good positive test. It is, however, far inferior to
the haemin test (p. 78) where that can be obtained, and of course in-
ferior to the identification of erythrocytes with the microscope, or to
the spectroscopic identification of the blood-pigment where the material
is suitable for this.
(4) Quantitative Estimation of Haemoglobin — (a) By Haldane's Modi-
fication of Gowers' Hcemoglobinometer. — Place in the graduated tube B
(Fig. 22.) an amount of water less than will ultimately be required to
dilute the blood to the required tint. Puncture the finger or lobe of
the ear with one of the small lancets in F, and fill the capillary pipette D
to a little beyond the mark 20. Wipe the point of the pipette and dab
it on a piece of filter-paper till the blood stands exactly at the mark.
Blow the blood into the water in B, and rinse the pipette with the water.
Attach the cap of tube G to a gas-burner. Introduce the rubber tube
into B nearly to the level of the water, and allow gas to pass for a few
seconds. Withdraw the tube while the gas is still passing. Immediately
close the end of B with the finger, and move the tube so that the
liquid passes from end to end of it at least a dozen times, to saturate
the haemoglobin with carbonic oxide. While this is being done, the
tube should be held in a cloth, otherwise it will become heated, and
liquid will spurt out when the finger is removed. Water is now added
* The formed elements of blood really contain no less than three ferments
of interest in this connection: (i) A catalase which decomposes peroxide of
hydrogen into water and molecular oxygen (i.e., oxygen not in the atomic
or nascent state). This reaction is given by both blood and pus. (2) An
oxydase (also spelled oxidase), which oxidizes guaiacum and similar substances
without the presence of hydrogen peroxide. This reaction is obtainable even
from aqueous extracts of leucocytes. (3) A peroxydase (also spelled peroxi-
dase) which causes the oxidation of these substances only in the presence of
hydrogen peroxide, a reaction also given by leucocytes. These ferments are
all inactivated iby boiling (Kastle).
PRACTICAL EXERCISES
drop by drop with the pipette stopper of the bottle E, which is used
for holding the water, the tube being inverted after each, addition,
till the tint in B is the same as that in A. In comparing the tubes,
they should be held against the light from the sky or from an opal
glass lamp-shade. It is necessary to transpose the tubes repeatedly.
The level at which the tints are equal is read off on B half a minute
after the addition of the last drop of water. Water is now again added
by drops till the tint in B is just roticeably weaker than in A, and the
mean of the two readings is taken. The result is the percentage actually
present of the average proportion of haemoglobin in the blood of healthy
adult males. Healthy women give an average of only 89 per cent.,
and healthy children an average of only 87 per cent., of the proportion
in men. The liquid in A is a i per cent, solution of blood containing
the average percentage of haemoglobin found in the blood of healthy
Fig. 22. — Haldane's Modification of Gowers' Haemoglobinometer.
adult males, and having an oxygen capacity of 18 5 per cent. — i.e.,
100 c.c. of the blood with which the standard was made would take
up in combination from air 18-5 c.c. of oxygen. The solution in A has
been saturated with carbonic oxide.
This method is probably more accurate than any other used in clinical
work, the error, in the hands of an experienced observer, not exceeding
i per cent.
(b) By Fleischl's Hcemometer (Fig. 23). — Fill with distilled water that
compartment a' of the small cylinder (above the stage) which is over
the tinted wedge. Put a little distilled water into the other compart-
ment a. Now prick the finger and fill one of the small capillary tubes
with blood. See that none of the blood is smeared on the outside of
the tube. Then wash all the blood into the water in compartment a,
and fill it to the brim with distilled water. By means of the milled
78 THE CIRCULATING LIQUIDS OF THE BODY
head T move the tinted wedge K till the depth of colour is the same
in the two compartments. The percentage of the normal quantity
of haemoglobin is given by the graduated scale P. For example, if the
reading is 90, the blood contains 90 per cent, of the normal amount;
if 100, it contains the normal quantity. The observations should be
made in a dark room, the white surface S, arranged below the compart-
ments a and a', being illuminated by a lamp. Or the instrument may
be placed in a small box, lighted by a candle. It is best that each result
should be the mean of two readings, one just too large and the other
just too small. In any case the instrument does not give readings
accurate to less than 5 per cent.
(c) Hoppe-Seyler's Method. — Two parallel-sided glass troughs are
used. In one is put a standard solution of oxy haemoglobin of known
strength, in the other a measured quantity of the blood to be
tested. The latter is diluted
K
with water until its tint
appears the same as that
of the standard solution,
when the troughs are placed
Fig. 23. — Fleischl's Hasmometer.
Fig. 24.— Crystals of Hamin
(Frey).
side by side on white paper.
From the quantity of water
added it is easy to calculate
the proportion of haemo-
globin in the undiluted
blood. Greater accuracy is obtained if the haemoglobin in the standard
solution and that of the blood are converted into carbonic oxide haemo-
globin by passing a stream of coal-gas through them.
(d) Tallquist's Method. — In this method the tint produced by a
drop of blood on a piece of white filter-paper is compared with a scale
representing 10 percentages of haemoglobin (from 10 to 100 per cent.).
The standard filter-paper is supplied in the form of a book with the
scale. To make an estimation, all that is necessary is to touch a drop
of blood with a piece of the filter-paper, and allow the blood to diffuse
slowly through the paper, so as to give an even stain. The position
of the stain is then determined by the scale; e.g., it may be deeper
than 90, but fainter than 100, in which case the percentage of haemo-
globin lies between 90 and 100. The method is by no means a very
accurateone, but more accurate than it appears at first sight.
(5) Microscopic Test for Blood-Pigment. — Put a drop of blood on a
slide. Allow the blood to dry, or heat it gently over a flame, so as to
evaporate the water. Add a drop of glacial acetic acid ; put on a cover-
PRACTICAL EXERCISES . 79
glass, and again heat slowly till the liquid just begins to boil. Take
the slide away from the flame for a few seconds, then heat it again for
a moment; and repeat this process two or three times. Now let the
slide cool, and examine with the microscope (high power). The small
black, or brownish-black, crystals of haemin will be seen (Fig. 24, p. 78).
This is an important test where only a minute trace of blood is to be
examined, as in some medico-legal cases. If a blood-stain is old, a
mimite crystal of sodium chloride should be added along with the
glacial acetic acid. Fresh blood contains enough sodium chloride.
A blood-stain on a piece of cloth may first of all be soaked in a small
quantity of distilled water, and the liquid examined with the spectro-
scope or the micro-spectroscope (a microscope in which a small spectro-
scope is substituted for the eyepiece). Then evaporate the liquid to
dryness on a water-bath, and apply the hasmin test. Or perform the
haemin test directly on the piece of cloth. In a fresh stain the blood-
corpuscles might be recognized under the microscope. Very few
liquids, however, are available for washing out the blood, as all ordinary
solutions, and even serum itself, cause laking of dried corpuscles
(Guthrie). Absolute alcohol, or 35 per cent, potassium hydroxide,
may be used to soak and rub up the cloth in.
CHAPTER III
THE CIRCULATION OF THE BLOOD AND LYMPH
THE blood can only fulfil its functions by continual movement.
This movement implies a constant transformation of energy; and in
the animal body the transformation of energy into mechanical work
is almost entirely allotted to a special form of tissue, muscle. In
most animals there exist one or more rhythmically contractile
muscular organs, or hearts, upon which the chief share of the work
of keeping up the circulation falls.
SECTION I. — PRELIMINARY ANATOMICAL AND PHYSICAL DATA.
Comparative. — In Echinus a contractile tube connects the two vascu-
lar rings that surround the beginning and end of the alimentary canal,
and plays the part of a heart. In the lower Crustacea and in insects
the heart is simply the contractile and generally sacculated dorsal
bloodvessel; in the higher Crustacea, such as the lobster, it is a well-
defined muscular sac situated dorsally. A closed vascular system is
the exception among invertebrates. In most of them the blood
passes from the arteries into irregular spaces or lacunae in the tissues,
and thence finds its way back to the heart. In the primitive vertebrate
heart five parts can be distinguished as we proceed from the venous
to the arterial end: (i) The sinus venosus, into which the great veins
open; (2) the auricular canal, from the dorsal wall of which is developed
— (3) the auricle; (4) the ventricle; (5) the bulbus arteriosus, from which
the chief artery starts (Fig. 25, p. 81). Amphioxus, the lowest verte-
brate, has a primitive lacunar vascular system; a contractile dorsal
bloodvessel serves as arterial or systemic heart, a contractile ventral
vessel as venous or respiratory heart. From the latter, vessels go to
the gills. Fishes possess only a respiratory heart, consisting of a venous
sinus, auricle, ventricle, and bulbus arteriosus. This drives the blood
to the gills, from which it is gathered into the aorta; it has thence to
find its way without further propulsion through the systemic vessels
Amphibians have a venous sinus, two auricles, a single rentricle, and
an arterial bulb; reptiles, two auricles and two incompletely-separated
ventricles. In birds and mammals the respiratory and systemic
hearts are completely separated. The former, consisting of the right
auricle and ventricle, propels the blood through the lungs; the latter,
consisting of the left auricle and ventricle, receives it from the pul-
monary veins, and sends it through the systemic vessels.
The sinus venosus seems to be represented in the mammalian heart
by certain small portions of tissue, especially the so-called sino-auricular
node, a little knot of primitive fibres near the mouth of the superior
80
ANATOMICAL AND PHYSICAL DATA
81
vena cava. The auricular canal is probably represented by the
auriculo-ventricular bundle (conveniently designated as the a. -v. bundle),
which will again be referred to in relation to the conduction of the heart-
beat from auricles to ventricles (p. 147). This bundle starts from a
clump of primitive tissue, the auriculo-ventricular node (a.-v. node)
at the base of the interauricular septum on the right side, below and
to the right of the coronary sinus, and runs down the interventricular
septum. The sino-auricular and the auriculo-ventricular nodes are
connected by fibres which run in the interauricular septum, so that it
may be considered that the primitive cardiac tube is still represented
from base to apex of the adult
mammalian heart, although only
by very slender threads of tissue,
amidst the massive secondary
developments of auricular and
ventricular muscle (Keith and
Flack).
General View of the Circulation
in Man. — The whole circuit of the
blood is divided into two portions,
very distinct from each other,
both anatomically and function-
ally— the respiratory or lesser
circulation, and the systemic or
greater circulation. Starting from
the left ventricle, the blood passes
along the systemic vessels — ar-
teries, capillaries, veins — and, on
returning to the heart, is poured
into the right auricle, and thence
into the right ventricle. From
the latter it is driven through the
pulmonary artery to the lungs,
passes through the capillaries of
these organs, and returns through
the pulmonary veins to the left
auricle and ventricle. The portal Fifl ^.-Diagram of Primitive Vertebrate
_.- .- •*•_ 1-1 OOT-T <^*-im Kin in cr H AQT111"AQ Trmniri in T l-nn
system, which gathers up the
blood from the intestines, forms
a kind of loop on the systemic
circulation. The lymph-current
is also in a sense a slow and stag-
nant side -stream of the blood -
circulation; for substances are
constantly passing from the
bloodvessels into the lymph -spaces, and returning, although after a com-
paratively long interval, into the blood by the great lymphatic trunks.
Physiological Anatomy of the Vascular System. — The heart is to be
looked upon as a portion of a bloodvessel which has been modified to
act as a pump for driving the blood in a definite direction. Morpho-
logically it is a bloodvessel; and the physiological property of auto-
matic rhythmical contraction which belongs to the heart in so eminent
a degree is, as has been mentioned (p. 80), an endowment of blood-
vessels in many animals that possess no localized heart. Even hi
some mammals contractile bloodvessels o'ccur; the veins of the bat's
wing, for example, beat with a regular rhythm, and perform the func-
tion of accessory hearts.
Heart, combining Features found in the
Eel, Dogfish, and Frog (Flack, after
Keith), a, Sinus venosus; b, auricular
canal; c, auricle; d, ventricle; e, bulbus
cordis; /, aorta; i-i, sino-auricular junc-
tion and venous valves; 2-2, junction of
canal and auricle; 3-3, annular part of
auricle; 5, bulbo-ventricular junction.
82 THE CIRCULATION OF THE BLOOD AND LYMPH
The whole vascular system is lined with a single layer of endothelial
cells. In the capillaries nothing else is present; the endothelial layer
forms the whole thickness of the wall. In young animals, at any rate,
the endothelial cells of the capillaries are capable of contracting when
stimulated; and changes in the calibre of these vessels can be brought
about in this way. The walls of the arteries and veins are chiefly
made up of two kinds of tissue, which render them distensible and
elastic: non-striped muscular fibres and yellow elastic fibres. The
muscular fibres are mainly arranged as a circular middle coat, which,
especially in the smaller arteries, is relatively thick. One conspicuous
layer of elastic fibres marks the boundary between the middle and
inner coats. In the larger arteries elastic laminae are also scattered
freely among the muscular fibres of the middle coat. The outer coat
is composed chiefly of ordinary connective tissue. The veins differ
from the arteries in having thinner walls, with the layers less distinctly
marked, and containing a smaller proportion of non-striped muscle
and elastic tissue ; although in some veins, those of the pregnant uterus,
for instance, and the cardiac ends of the large thoracic veins, there is
a greater development of muscular tissue. Further, and this is of prime
physiological importance, valves are present in many veins. These
are semilunar folds of the internal coat projecting into the lumen in
such a direction as to favour the flow of blood towards the heart,
but to check its return. In some veins, as the venae cavae, the pulmonary
veins, the veins of most internal organs, and of bone, there are no valves ;
in the portal system they are rudimentary in man and the great majority
of mammals. The valves are especially well marked in the lower limbs,
where the venous circulation is uphill. When a valve ceases to perform
its function of supporting the column of blood between it and the
valve next above, the foundation of varicose veins is laid; the valve
immediately below the incompetent one, having to bear up too great
a weight of blood, tends to yield in its turn, and so the condition spreads.
The smallest veins, or venules, are very like the smallest arteries, or
arterioles, but somewhat wider and less muscular. The transition
from the capillaries to the arterioles and venules is not abrupt, but
may be considered as marked by the appearance of the non-striped
muscular fibres, at first scattered singly, but gradually becoming closer
and more numerous as we pass away from the capillaries, until at length
they form a complete layer.
In the heart the muscular element is greatly developed and differ-
entiated. Both histologically and physiologically the fibres seem to
stand between the striated skeletal muscle and the smooth muscle. In
the mammal the cardiac muscular fibres are generally described as
made up of short oblong cells, devoid of a sarcolemma, often branched,
and arranged in anastomosing rows, each cell having a single nucleus
in the middle of it. But it has recently been shown that the muscle
fibrils run right through the apparent cell boundaries, and form a con-
tinuous sheet of tissue anastomosing in every direction. The fibres
are transversely striated, but the striae are not so distinct as in skeletal
muscle. A sarcolemma is not absent, although it is more delicate
than in skeletal muscle, and perhaps of a different nature. Many
fibres pass from one auricle to the other, and from one ventricle to the
other.
In the frog's heart the muscular fibres are spindle-shaped, like those
of smooth muscle, but transversely striated, like those of skeletal
muscle. From the sinus to the apex of the ventricle there is a con-
tinuous sheet of muscular tissue.
ANATOMICAL AND PHYSICAL DATA 83
The problems of the circulation are partly physical, partly vital.
Some of the phenomena observed in the blood-stream of a living
animal can be reproduced on an artificial model ; and they may justly
be called the physical or mechanical phenomena of the circulation.
Others are essentially bound up with the properties of living tissues ;
and these may be classified as the vital or physiological phenomena of
the circulation. The distinction, although by no means sharp and
absolute, is a convenient one — at least, for purposes of description;
and as such we shall use it. But it must not be forgotten that the
physiological factors play into the sphere of the physical, and the
physical factors modify the physiological. Considered in its
physical relations, the circulation of the blood is the flow of a liquid
along a system of elastic tubes, the bloodvessels, under the influence
of an intermittent pressure produced by the action of a central
pump, the heart. But the branch of dynamics which treats of the
movement of liquids, or hydrodynamics, is one of the most difficult
parts of physics, and even in the physical portion of our subject we
are forced to rely chiefly on empirical methods. It would, therefore,
not be profitable to enter here into mathematical theory, but it may
be well to recall to the mind of the reader one or two of the simplest
data connected with the flow of liquids through tubes:
Torricelli's Theorem. — Suppose a vessel filled with water, the level
of which is kept constant; the velocity with which the water will
escape from a hole in thejside of the vessel at a vertical depth h below
the surface will be v= *2gh, where g is the acceleration produced by
gravity.* In other words, the velocity is that which the water would
have acquired in falling in vacua through the distance h. This formula
was deduced experimentally by Torricelli, and holds only when the
resistance to the outflow is so small as to be negligible. The reason of
this restriction will be easily seen, if we consider that when a mass
ra of water has flowed out of the opening, and an equal mass m has
flowed in at the top to maintain the old level, everything is the same
as before, except that energy of position equal to that possessed by
a mass m at a height h has disappeared. If this has all been changed
into kinetic energy E, in the form of_visible motion of the escaping
water, then ~E = %mv2=mgh, i.e., v= *J-2gh. If, however, there has been
any sensible resistance to the outflow, any sensible friction, some of
the potential energy (energy of position) will have been spent in over-
coming this, and will have ultimately been transformed into the kinetic
energy of molecular motion, or heat.
Flow of a Liquid through Tubes. — Next let a horizontal tube of uni-
form cross-section be fitted on to the orifice. The velocity of outflow
will be diminished, for resistances now come into play. When the
liquid flowing through a tube wets it, the layer next the wall of the
tube is prevented by adhesion from moving on. The particles next
this stationary layer rub on it, so to speak, and are retarded, although
not stopped altogether. The next layer rubs on the comparatively
slowly moving particles outside it, and is also delayed, although not
so much as that in contact with the immovable layer on the walls of
* I.e., the amount added per second to the velocity of a falling body
(g = 32 feet).
84
THE CIRCULATION OF THE BLOOD AND LYMPH
the tube. In this way it comes about that every particle of the liquid
is hindered by its friction against others — those in the axis of the tube
least, those near the periphery most — and part of the energy of position
of the water in the reservoir is used up in overcoming this resistance,
only the remainder being transformed into the visible kinetic energy
of the liquid escaping from the open end of the tube.
If vertical tubes be inserted at different points of the horizontal
tube, it will be found that the water stands at continually decreasing
heights as we pass away from the reservoir towards the open end of
the tube. The height of the liquid in any of the vertical tubes indicates
the lateral pressure at the point at which it is inserted ; in other words,
the excess of potential energy, or energy of position, which at that
point the liquid possesses as compared with the water at the free end,
where the pressure is zero. If the centre of the cross-section of the
free end of the tube be joined to the centres of all the menisci, it will
be found that the line is a straight line. The lateral pressure at any
point of the tube is therefore proportional to its distance from the free
end. Since the same quantity of water must pass through each cross-
section of the horizontal tube in a given time as flows out at the open
end, the kinetic energy of the liquid at every cross-section must be
constant and equal to \mvi,
where v is the mean velocity
(the quantity which escapes in
unit of time divided by the
cross-section) of the water at
the free end.
Just inside the orifice the
total energy of a mass m of
water is mgh; just beyond it
at the first vertical tube, mgh'
+ %mvz, where h' is the lateral
pressure. On the assumption
that between the inside of the
orifice and the first tube no
energy has been transformed
into heat (an assumption
the more nearly correct the
smaller the distance between
it and the inside of the orifice is made), we have mgh=mgh' + %mv2,
i.e., %mv2 = mg(h-h'). In other words, the portion of the energy of
position of the water in the reservoir which is transformed into the
kinetic energy of the water flowing along the horizontal tube is measured
by the difference between the height of the level of the reservoir and
the lateral pressure at the beginning of the horizontal tube — that is,
the height at which the straight line joining the menisci of the vertical
tubes intersects the column of water in the reservoir. Let H represent
the height corresponding to that part of the energy of position which
is transformed into the kinetic energy of the flowing water. H is easily
calculated when the mean velocity of efflux is known. For v= */2gH
by Torricelli's theorem (since none of the energy corresponding to H
-.2
is supposed to be used up in overcoming friction), or H=— . At the
second tube the lateral pressure is only h". The sum of the visible
kinetic and potential energy here is therefore \mv* + mgh". A quantity
of energy mg(h' - h") must have been transformed into heat owing to
the resistance caused by fluid friction in the portion of the horizontal
Fig. 26. — Diagram to illustrate Flow of
Water along a Horizontal Tube connected
with a Reservoir.
ANATOMICAL AND PHYSICAL DATA 85
tube between the first two vertical tubes. In general the energy of
position represented by the lateral pressure at any point is equal to
the energy used up in overcoming the resistance of the portion of the
path beyond this point.
Velocity of Outflow. — It has been found by experiment that v, the.
mean velocity of outflow, when the tube is not of very small calibre,
varies directly as the diameter, and therefore the volume of outflow
as the cube of the diameter. In fine capillary tubes the mean velocity
is proportional to the square, and the volume of outflow to the fourth
power of the diameter (Poiseuille). If, for example, the linear velocity
of the blood in a capillary of 10 p, in diameter is \ mm. per sec., it will
be four times as great (or 2 mm. per sec.) in a capillary of 20 p diameter,
and one-fourth as great (or £ mm. per sec.) in a capillary of 5 p. diameter,
the pressure being supposed equal in all. The volume of outflow per
second is obtained by multiplying the cross-section by the linear
velocity. The cross-section of a circular capillary, 10 /* in diameter,
is TT (5 x TfiW)2 = » sav> TaioiF scl- mm- The outflow will be ^ gsffo x i
= 05^0 cub. mm. per sec. The outflow from the capillary of ,».o /*
diameter would be sixteen times as much, from the 5 /* capillary only
one-sixteenth as much. Some idea of the extremely minute scale
on which the blood-flow through a single capillary takes place may
be obtained if we consider that for the capillary of 10 /* diameter a
flow of -2500TJ cub. mm. per sec. would scarcely amount to I cub. mm
in six hours, or to i c.c. in 250 days.
When the initial energy is obtained in any other way than by means
of a ' head ' of water in a reservoir — say, by the descent of a piston
which keeps up a constant pressure in a cylinder filled with liquid —
the results are exactly the same. Even when the horizontal tube is
distensible and elastic, there is no difference when once the tube has
taken up its position of equilibrium for any given pressure, and that
pressure does not vary.
Flow with Intermittent Pressure. — When this acts on a rigid tube,
everything is the same as before. When the pressure alters, the
flow at once comes to correspond with the new pressure. Water
thrown by a force-pump into a system of rigid tubes escapes at every
stroke of the pump in exactly the quantity in which it enters, for
water is practically incompressible, and the total quantity present
at one time in the system cannot be sensibly altered. In the intervals
between the strokes the flow ceases; in other words, it is intermittent.
It is very different with a system of distensible and elastic tubes.
During each stroke the tubes expand, and make room for a portion
of the extra liquid thrown into them, so that a smaller quantity flows
out than passes in. In the intervals between the strokes the distended
tubes, in virtue of their elasticity, tend to regain their original calibre.
Pressure is thus exerted upon the liquid, and it continues to be forced
out, so that when the strokes of the pump succeed each other with
sufficient rapidity, the outflow becomes continuous. This is the state
of affairs in the vascular system. The intermittent action of the
heart is toned down in the elastic vessels to a continuous steady flow.
SECTION II. — THE BEAT OF THE HEART IN ITS PHYSICAL OR
MECHANICAL RELATIONS.
Events in the Cardiac Cycle. — In the frog's heart the contraction
can be seen to begin about the mouths of the great veins which open
into the sinus venosus. Thence it spreads in succession over the
86 THE CIRCULATION OF THE BLOOD AND LYMPH
sinus and auricles, hesitates for a moment at the auriculo- ventric-
ular junction, and then with a certain suddenness invades the
ventricle. In the mammalian heart the contraction likewise com-
mences, so far as can be ascertained by inspection or the study of
tracings, in the region near the mouths of the veins opening into the
auricles. It will be seen, when the question of the origin of the
rhythmical beat is being discussed (p. 141), that the actual starting-
point is probably the sinus tissue of the right auricle (p. 142) near the
opening of the superior vena cava, which is richly provided with
muscular fibres akin to those of the heart. But the wave advances
so rapidly that it is difficult to trace in its course a regular progress
from base to apex, although the ventricular beat undoubtedly
follows that of the auricle, and in a heart beating normally the
electrical change associated with contraction of the ventricle
begins at the base, then reaches the apex (p. 853), and finally passes
towards the orifices of the great arteries.
The most conspicuous events in the beat of the heart, in their
normal sequence, are: (i) the auricular contraction or systole, (2) the
ventricular contraction or systole, each followed by relaxation. (3) the
pause. The auricles, into which, "and beyond which into the ven-
tricles, blood has been flowing during the pause from the great
thoracic veins, contract sharply, the right, perhaps, a little before
the left. The contraction begins in the muscular tissue that
surrounds the orifices of the veins, so that these, destitute of valves
as they are, are functionally, at least, if not anatomically, sealed up
for an instant, and regurgitation of blood into them is to a great
extent, if not entirely, prevented. Apparently, complete closure
of the inferior cava is unnecessary, the pressure of the blood in it
being sufficiently high to hinder any important back-flow. The
action of the circular fibres of the veins in closing their orifices is
reinforced by the contraction of a band of muscle (the tania ter-
minalis) in the roof of the right auricle. This band compresses
especially the mouth of the superior vena cava. The filling of the
ventricles is thus completed. The actual amount of extra blood
injected into the ventricles by the auricular contraction is not large.
The ventricles are already nearly charged, but the auricles, so to
speak, ram the charge home. The ventricular contraction follows
hard on the relaxation of the auricles. The mitral and tricuspid
valves, whose strong but delicate curtains have during the diastole
been hanging down into the ventricles and swinging freely in the
entering current of blood, are floated up as the intraventricular
pressure begins to rise, so that, in the first moment of the sudden
and powerful ventricular systole, the free edges of their segments
come together, and the auriculo-ventricular orifices are completely
closed (Fig. 98, p. 206). In the measure in which the pressure in the
contracting ventricles increases, the contact of the valvular seg-
MECHANICS OF THE HEART-BEAT 87
merits becomes closer and more extensive; and their tendency to
belly into the auricles is opposed by the pull of the chordae tendineae,
whose slender cords, inserted into the valves from border to base, are
kept taut, in spite of the shortening of the ventricles by the con-
traction of the papillary muscles. The arrangement and connec-
tions of the muscular fibres of the heart are such that during the
auricular systole the auriculo-ventricular groove moves towards the
base of the heart, while during the systole of the ventricles it moves
towards the apex, which constitutes a relatively fixed point on
account of the mutual action of the numerous fibres which converge
here and constitute the ' whorl.' The line joining the apex and
the origin of the aorta does not shorten when the ventricles contract,
but all parts of the heart are drawn towards this line. The apex is,
therefore, pushed forwards, while the rest of the ventricular surface
is being drawn inwards. During the systole, the ventricles change
their shape in such a way that their combined cross-section — which
in the relaxed state is a rough ellipse with the major axis from right
to left — becomes approximately circular, and they then form a right
circular cone. As soon as the pressure of the blood within the con-
tracting ventricles exceeds that in the aorta and pulmonary artery
respectively, the semilunar valves, which at the beginning of the
ventricular systole are closed, yield to the pressure, and blood is
driven from the ventricles into these arteries.
The ventricles are more or less completely emptied during the
contraction, which seems still to be maintained for a short time after
the blood has ceased to pass out. The contraction is followed
by sudden relaxation. The intraventricular pressure falls. The
lunules of the semilunar valves slap together under the weight of the
blood as it attempts to regurgitate, the corpora Arantii seal up the
central chink, and the aorta and pulmonary artery are thus cut off
from the heart. Then follows an jnterval during which the whole
heart is at rest, namely, the interval between the end of the relaxa-
tion of the ventricles and the beginning of the systole of the auricles.
This constitutes the pause. The whole series of events is called a
cardiac cycle or revolution (see Practical Exercises, p. 201).
It will be easily understood that the time occupied by any one of
the events of the cardiac cycle is not constant, for the rate of the
heart is variable. If we take about 70 beats a minute as the average
normal rate in a man, the ventricular systole will occupy about
0-3 second; the diastole,* including the ventricular relaxation, about
* The term ' diastole ' is variously used, as meaning the pause, the pause
plus the period during which relaxatidn is occurring, or the period of re-
laxation alone. We shall employ it in the second sense. Henderson refers
to the period during which the ventricular muscle is at rest, from the end of
its relaxation to the onset of the auricular systole, as the ' diastasis ' and the
period during which the relaxation is taking place as the 'diastole,' a termin-
ology which seems worthy of general adoption.
88 THE CIRCULATION OF THE BLOOD AND LYMPH
0-5 second. The systole of the auricle is one-third as long as that of
the ventricle.
This rhythmical beat of the heart is the ground phenomenon of
the circulation. It reveals itself by certain tokens — sounds, surface-
movements or pulsations, alterations of the pressure and velocity of
the blood, changes of volume in parts — all periodic phenomena,
continually recurring with the same period as the heart -beat, and all
fundamentally connected together. And if we hold fast the idea
that when we take a pulse-tracing, or a blood-pressure curve, or a
plethysmographic record, we are really investigating the same fact
from different sides, we shall be able, by following the cardiac rhythm
and its consequences as far as we can trace them, to hang upon a
single thread many of the most important of the physical phenom-
ena of the circulation.
The Sounds of the Heart. — When the ear is applied to the chest, or
to a stethoscope placed over the cardiac region, two sounds are
heard with every beat of the heart. They follow each other closely,
and are succeeded by a period of silence. The dull booming ' first
sound ' is heard loudest in a region which we shall afterwards have
to speak of as that of the ' cardiac impulse ' (p. 90) ; the short, sharp,
' second sound ' over the junction of the second right costal cartilage
with the sternum.
The heart-sounds can be registered by placing over the chest a
microphone receiver connected with a string galvanometer. The
magnified sounds are translated into electrical changes which cause
movements of the fibre of the galvanometer, and the movements are
photographed on a travelling plate (Einthpven). The record is called
a cardiophonogram. When this is studied, a third sound can be
detected, and it is probable that it is present in all persons, although it
is as a rule inaudible to auscultation. It occurs early in diastole very
shortly after the second sound. In those persons in whom it is audible
it is most distinct over the region of cardiac impulse. It is described
as softer and of lower pitch than the second sound (Thayer).
There has been much discussion as to the cause of the first sound.
That a sound corresponding with it in time is heard in an excised
bloodless heart when it contracts is certain ; and therefore the first
sound cannot be exclusively due, as some have asserted, to vibra-
tions of the auriculo-ventricular valves when they are suddenly
rendered tense by the contraction of the ventricles, for in a bloodless
heart the valves are not stretched. Part of the sound must accord-
ingly be associated with the muscular contraction as such.
Again, the fact that the first sound is heard during the whole, or
nearly the whole, of the ventricular systole is against the idea that
it is exclusively due to the vibrations of membranes like the valves,
which would speedily be damped by the blood and rendered in-
audible. But while there is good reason to believe that the vibra-
tion of the suddenly-contracted ventricles is the fundamental factor,
the shock sets up vibrations also in the blood, the chest-wall, and
MECHANICS OF THE HEART-BEAT 89
perhaps the resonant tissue of the lungs. Further, as we shall see
later on (p. 760), the sound caused by a contracting muscle readily
calls forth sympathetic resonance in the ear, and the peculiar boom-
ing character of the first sound may be due to the superposition of
these various resonance tones upon the muscular note. But, in
addition, the vibration of the auriculo-ventricular valves un-
doubtedly contributes to the production of the sound, and some
observers have been able to distinguish in the first sound the valvular
and the muscular elements, the former being higher in pitch than the
latter, but a minor third below the second sound. In the excised
empty heart the deeper tone of the first sound is alone heard, while
the higher note is elicited when in a dead heart the auriculo-ventric-
ular valves are suddenly put under tension (Haycraft) . When the
mitral valve is prevented from closing by experimental division of
the chordae tendineas, or by pathological lesions, the first sound of
the heart is altered or replaced by a ' murmur.' This evidence is
not only important as regards the physiological question, but of
great practical interest from its bearing on the diagnosis of cardiac
disease. It may be added that the point of the chest-wall at which
the first sound is most easily recognized is also the point at which a
changed sound or murmur connected with disease of the mitral valve
is most distinctly heard. The sound is, therefore, best conducted
from the mitral valve along the heart to the point at which it comes
in contact with the wall of the chest. Changes in the first sound con-
nected with disease of the tricuspid valve are heard best, in the com-
paratively rare cases where they can be distinctly recognized, in the
third to the fifth interspace, a little to the right of the sternum.
The second sound is caused by the vibrations of the semilunar
valves when suddenly closed, ' the recoiling blood forcing them back,
as one unfurls an umbrella, and with an audible check as they
tighten ' (Watson). The sharpness of its note is lost, and nothing
but a rushing noise or bruit can be heard, when the valves are hooked
back and prevented from closing. It is altered, or replaced by a
murmur, when the valves are diseased. As there is a mitral and a
tricuspid factor in the first sound, so there is an aortic and a pul-
monary factor in the second. The place where the second sound is
best heard (over the junction of the second right costal cartilage and
sternum) is that at which any change produced by disease of the
aortic valves is most easily recognized. The sound is conducted up
from the valves along the aorta, which comes nearest to the surface
at this point. Changes connected with disease of the pulmonary
valves are most readily detected over the second left intercostal
space near the edge of the sternum, for here the pulmonary artery
most nearly approaches the chest- wall. The first sound is ' systolic '
— that is, it occurs during the ventricular systole; the second is
' diastolic/ beginning at the commencement of the diastole
THE CIRCULATION OF THE BLOOD AND LYMPH
Various explanations of the third sound have been given, but, as
the authors who have studied it are not even agreed as to whether it
is produced at the auriculo-ventricular orifices or at the aortic and
pulmonary orifices, it would not be useful to discuss them at present.
The Cardiac Impulse. — A surface-movement is seen, or an impulse
felt, at every cardiac contraction in various situations where the
heart or arteries approach the surface. The pulsation, or impulse,
of the heart, often styled the apex-beat, is usually most distinct to
sight and touch in a small area lying in the fifth left intercostal
space, between the mammary and the parasternal line,* and gener-
ally, in an adult, about an inch and a half to the sternal side of the
former. It is due to the systolic hardening of the ventricles, which
are here in contact with the chest-wall, the contact being at the
same time rendered closer by their change of shape, and by a slight
movement of rotation of
the heart from left to right
during the contraction
(Practical Exercises,
p. 207). When the left
ventricle is in contact with
the chest at the position of
the apex-beat, as is usually
the case, an important
element in the impulse is
the actual forward thrust
of the apex. When the
apex-beat corresponds in
position with the right
ventricle, there is no
actual forward movement,
although the hardening of
the ventricle may be felt as a thrust by the ringer. Even in health
the position of the impulse varies somewhat with the position of
the body and the respiratory movements. In children it is usually
situated in the fourth intercostal space. In disease its displacement
is an important diagnostic sign, and may be very marked, especially
in cases of effusion of fluid into the pleural cavity. It is sometimes,
though not invariably, a little lower in the standing than in the
sitting position, and shifts an inch or two to the left or right when
the person lies on the corresponding side.
Various instruments, called cardiographs, have been devised for
magnifying and recording the movements produced by the cardiac
impulse. Marey's cardiograph (Fig. 27) consists essentially of a small
* The mammary line is an imaginary vertical line supposed to be drawn
on the chest through the middle point of the clavicle. It usually, but not
necessarily, passes through the nipple. The parasternal line is the vertical
line lying midway between the mammary line and the corresponding border
of the sternum.
Fig. 27. — Diagram of Marey's Cardiograph.
MECHANICS OF THE HEART -BEAT gi
chamber, or tambour, filled with air, and closed at one end by a flexible
membrane carrying a button, which can be adjusted to the wall of the
chest. This receiving tambour is connected by a tube with a recording
tambour, the flexible plate of which acts upon a lever writing on a
travelling surface — a uniformly-rotating drum, for example — covered
with smoked paper. Any movement communicated to the button
forces in the end of the tambour to which it is attached, and thus
raises the pressure of the air in it and in the recording tambour; the
flexible plate of the tatter moves in response, and the lever transfers
the movement to the paper. The tracing, or cardiogram, obtained in
this way shows a small elevation corresponding to the auricular systole,
succeeded by a large abrupt rise corresponding to the beginning of
the first sound, and caused by the ventricular systole. This ventricular
elevation is the essential portion of the curve ; it is alone felt by the
palpating hand, and the auricular elevation is often absent from the
cardiogram in man. The rise is maintained, with small secondary
oscillations, for about 03 of a second in a tracing from a normal man,
then gives way to a sudden de-
scent, that marks the relaxation
of the ventricles, the beginning
of the second sound, and the
closure of the semilunar valves.
An interval of about 0-5 second
elapses before the curve begins
again to rise at the next auricular
contraction.
Such was the interpretation
which Chauveau and Marey put
upon their tracings. . Although
neither their results nor their
deductions from them have Pi& 28.— Cardiogram taken with Marey s
escaped the criticism of succeed- Cardiograph A, auricular systole;
ine investigators it is doubtful V> ventncular systole ; D, diastole.
whether *Sv Seonate Reason The arrow shows the directi°Q * which
whether any adequate reason the tracing is to be read.
has been brought forward for
discarding them, and Chauveau has furnished further proofs of their
accuracy. The difficulties that beset the subject are great, for the
cardiogram is a record of a complex series of events. The very rapid
variation of pressure within the ventricles, the change of volume and
of shape of the heart, the slight change of position of its apex, must
all leave their mark upon the curve, which is besides distorted by the
resistance of the elastic chest-wall, the inertia of the recording lever,
and the compression of the air in the connecting tubes. It is only by
comparing in animals the cardiographic record with the changes of
blood-pressure in the heart and arteries that our present degree of
knowledge of the human cardiogram has been attained. Could we
register directly the fluctuations of pressure in the interior of the human
heart, the cardiographic method would be rarely employed. For
cl.nical purposes the receiving tambour can be advantageously replaced
by a small glass funnel or a small metal cup, the open end of which is
applied without a membrane over the cardiac impulse, the stem being
connected with the recording tambour. In cases in which the right
ventricle is in contact with the chest-wall at the position of the apex-
beat the cardiogram is ' inverted ' — that is to . say, the chest-wall is
drawn in during systole and protruded during diastole of the ventricles.
Inversion of the cardiogram is, therefore, not an infallible sign of the
pathological condition known as adherent pericardium (Mackenzie).
Aur:\~- J I; A ,
92
Endocardiac Pressure. — The function of the heart is to maintain
an excess of pressure in the aorta and pulmonary artery sufficient to
overcome the friction of the whole vascular channel, and to keep up
the flow of blood. So long as the semilunar valves are closed, most
of the work of the contracting ventricles is expended in raising the
pressure of the blood within them. At the moment when blood
begins to pass into the arteries, nearly all the energy of this blood is
potential; it is the energy of a liquid under pressure. During a
cardiac cycle the pressure in the cavities of the heart, or the endo-
cardiac pressure, varies from moment to moment, and its variations
afford important
data for the study
of the mechanics of
the circulation.
Manometers. — For
the study of the endo-
cardiac pressure, the
ordinary mercurial
manometer (p. no)
is unsuitable, since,
owing to the rela-
tively great amount
of work required to
produce a given dis-
placement of the mer-
cury, it does not
readily follow rapid
changes of pressure,
and the mercurial
column, once dis-
placed, continues for
a time to execute
vibrations of its own,
which are compoun-
ded with the true oscillations of blood-pressure. But by introducing
in the connection between the manometer and the heart a valve so
arranged as to oppose the passage of blood towards the heart, while it
favours its passage towards the manometer, the maximum pressure
attained in the cardiac cavities during the cycle may be measured with
considerable accuracy. When the valve is reversed the apparatus
becomes a minimum manometer. In this way it has been found that
in large dogs the pressure in the left ventricle may rise as high as 230
to 240 mm. of mercury, and sink as low as — 30 to - 50 mm. ; while in
the right ventricle it may be as much as 70 mm., and as little as
— 25 mm. In the right auricle a maximum pressure of 20 mm. of
mercury has been recorded, and a minimum pressure of — 10 mm. or
even less. But these results were obtained under somewhat exceptional
experimental conditions, and the normal maximum pressures in the
heart cavities in man are probably not so high, especially in the right
auricle and ventricle.
Our knowledge of the maximum and minimum pressure attained
in the cavities of the heart, even if it were far more precise than it
actually is, would only carry us a little way in the study of the endo-
cardiac pressure-curve, for it would merely tell us how far above the
Vt nt: V
AS VS
Fig. 29. — Curves of Endocardiac Pressure taken with
Cardiac Sounds. Aw., auricular curve; Vent., ven-
tricular curve; AS, period of auricular systole, in-
cluding relaxation; VS, of ventricular systole, including
relaxation; D, pause.
MECHANICS OF THE HEART-BEAT
93
base-line of atmospheric pressure the curve ascends, and how far below
the base-line it sinks. To exhaust the problem, we require to have
tracings of the exact form of the curve for each of the cavities of the
heart, and to know the time -relations of the curves so as to be able to
compare them with each other, and with the pressure-curves of the great
arteries and great veins. To obtain satisfactory tracings of the swiftly-
changing endocardiac pressure i
is a task of the highest techni- /
cal difficulty, and it is only in vvwvzittAJ.
very recent years that it has
been accomplished, with any ap-
proach to accuracy by the use
of elastic manometers, in which
the blood-pressure is counter-
balanced, not by the weight of
a column of liquid aSKin.the Fig. 3o.-DiagrL of Hurthle's Elastic ManoT
mercurial manometer, but by J^g, r> °small chamber covered by mem.
the resistance to compression brane; /t tube communicating with interior
01 a small column of air or the Of heart; L, compound lever to magnify the
tension of an elastic disc or of movements of the membrane,
a spring. Modifications in the
nature and dimensions of the elastic resistance of the recording apparatus
and of the size of the cavity have produced successive improvements, as,
e.g., in the manometers of Hiirthle (Fig. 30).
The penetrating analysis of the principles of manometer construction
by Frank has recently stimulated renewed investigation of the whole
subject with the aid of instruments whose movements are optically re-
Fig. 31. — Diagram of Optical Manometer (Wiggers).
A is a vertical glass tube surmounted by a hollow
brass cylinder, B, which contains a stopcock, C,
whose lumen comes into apposition with a plate,
a, having a small opening in it. By opening the
stopcock more or less, the pulsations will be ' damped '
to a smaller or greater extent. Above a the cylinder
ends in a segment capsule b (i.e., a capsule cut away
at one side) 3 mm. in diameter, covered with rubber
dam. Upon this a small piece of celluloid carrying
a little mirror, c, is fastened, so that it pivots on the
chord side of the capsule. Over the capsule and its
recording mirror is mounted a support bearing an
inclined reflecting mirror, E, adjustable about a
horizontal axis by a screw, so that the image of the
recording mirror appears within it. Upon this
image a strong light is focussed. The incident rays
are doubly reflected, as shown in the figure, and the
movements of the capsule are thus greatly magnified.
The beam of light is photographed on a moving
plate.
c--
corded on a photographic plate, so as to eliminate all unnecessary fric-
tion. Fig. 31 is a diagram of the manometer devised by Wiggers on
this principle.
Hurthle's spring manometer consists of a sn^all drum covered with
an indiarubber membrane, loosely arranged so as not to vibrate with
a period of its own. The drum is connected with the heart or with
a vessel, and the blood -pressure is transmitted to a steel spring by
means of a light metal disc fastened on the membrane. The spring
94 THE CIRCULATION OF THE BLOOD AND LYMPH
acts on a writing lever. The instrument is so constructed that for a
given change of pressure the quantity of liquid displaced is as small
as possible, and it is on this that its capacity to follow sudden varia-
tions of pressure chiefly depends. The manometer is connected with
the cavity of the heart by an appropriately curved cannula of metal
or glass, which, after being filled with some liquid that prevents co-
agulation (Practical Exercises, p. 211), is pushed through the jugular
vein into the right auricle or ventricle, or through the carotid artery
and aorta into the left ventricle. Some observers fill only the cannula
with fluid, and leave the capsule of the elastic manometer and as much
of the connections as possible full of air. Others fill the whole system
with liquid. And around the question of the relative merits of ' trans-
mission ' by liquid and by air has raged a controversy which, however,
now shows signs of coming to an end. For there is reason to suppose
that the character of the curves obtained is modified among other
circumstances by the manner in which the pressure is transmitted, as
it is certainly modified by the dimensions and mass of the moving parts
and the method of recording. As Wiggers has pointed out, the differ-
ences in the records obtained by different observers, even with the latest
methods of optical registration, are determined largely by the sensitive-
ness and degree of damping of the manometer.
The Ventricular Pressure-Curve. — Thus, the pressure-curve of the
ventricle, according to most of those who have employed mano-
meters with liquid transmission and small inertia of the moving
parts (Fig. 33), remains after the first abrupt rise, which undoubtedly
corresponds to the ventricular systole, well above the abscissa line
for a considerable time, and then 'descends somewhat less suddenly
than it rose. This systolic ' plateau,' although usually broken by
minor heights and hollows, which may be partly due to inertia oscilla-
tions of the liquid or the recording apparatus, would indicate that
the ventricular pressure, after its first swift rise, maintained itself at
a considerable height throughout the greater part of the systole.
The tracings yielded by most of the manometers with air trans-
mission show the same suddenness in the first part of the upstroke
and the last part of the descent — that is, the same abruptness
in the beginning of the contraction and the end of the relaxa-
tion. But they differ totally in the intermediate portion of the
curve, which, climbing ever more gradually as it nears its apex,
remains but a moment at the maximum, then immediately descend-
ing forms a ' peak/ and not a plateau. It ought to be distinctly
understood, however, that the use of the term ' plateau ' must not be
taken to imply that the pressure remains constant and the curve
parallel to the abscissa during this interval.
Wiggers, using the optical method of recording the pressure-
curve in the right ventricle (p. 93), finds that when the auricular
pressure and the pressure in the pulmonary artery are normal the
curve of intraventricular pressure may be divided into (i) an auric-
ular period; (2) a period of rising pressure while the ventricle is
contracting and its cavity is closed by the auriculo- ventricular and
semilunar valves; (3) an ejection period during which the pressure
MECHANICS OF THE HE ART -BE AT
95
still rises, reaches a summit, and then slowly falls; and (4) a relaxa-
tion period (Fig. 32).
Without entering further into a technical discussion, we may say
Gtrotid
Fig. 32. — Intraventricular Pressure Curves with Optical Recording (Wiggers). Three
types of normal curves are reproduced, taken with manometers of different
degrees of sensitivene'ss. The second at the left-hand side was taken with the
least sensitive, a — b, auricular systolic; 6 — d, isometric period, during which
the auriculo-ventricular and the semilunar valves are both closed; d — /, ejection
period; after/, diastole.
the bulk of the evidence goes to show that the plateau is not, as the
advocates of the peak have claimed, an artificial phenomenon, but
does in reality correspond to that continuation of the systole of the
Fig- 33- — Simultaneous Record of Pressure in Left Ventricle (V) and Aorta (A).
(Hurthle.) The tracings were taken with elastic manometers; o indicates a
point just before the closure of the mitral valve; i, the opening of the semilunar
valve ; 2, beginning of the relaxation of the ventricle ; 3, the closure of the semi-
lunar valve; 4, the opening of the mitral valve. The ventricular curve shows
a ' plateau.'
ventricle, that dogged grip, if we may so phrase it, which it seems to
maintain upon the blood after the greater portion of it has been
expelled.
g6 THE CIRCULATION OF THE BLOOD AND LYMPH
This conclusion is essentially in accordance with the results of
Chauveau and Marey, obtained long ago by means of their" ' cardiac
sound,' which was in principle an elastic manometer.
It consisted of an ampulla of indiarubber, supported on a frame-
work, and communicating with a long tube, which was connected with
a recording tambour. The ampulla was introduced into the heart (of
a horse) through the jugular vein or carotid artery in the way already
described. Sometimes a double sound was employed, armed with
two ampullae, placed at such a distance from each other that when
one was in the right ventricle the other was in the auricle of the same
side. Each ampulla communicated by a separate tube in the common
stem of the instrument with a recording tambour, and the writing
points of the two tambours were arranged in the same vertical line.
When any change in the blood-pressure takes place, the degree of
compression of the ampullae is altered, and the change is transmitted
along the air-tight connections to the recording tambours.
On most of the endocardiac pressure tracings taken with modern
manometers, whether the curves belong to the type of the peak or of
the plateau, no sudden change of curvature, no nick, or crease, or
undulation reveals the moment of opening or closure of any valve.
This has been considered by some writers a striking tribute to the
smooth working of the cardiac pump. There is reason to think,
however, that the smoothness of the curve is still in some degree
artificial, and on some of the records obtained by optical methods
(Fig. 32) indications of changes of curvature, associated with the
action of the valves, may be observed. But even in the absence of
such indications, by experimentally graduating a pair of elastic
manometers, and obtaining with them simultaneous records of the
pressure in auricle and ventricle, or by using a ' differential ' mano-
meter, in which the pressures in two cavities are qpposed to each
other, so that the movement of the membrane corresponds to their
difference, we can calculate at what points of the ventricular curve
the pressure is just greater than and just less than the pressure in the
auricle. The first point, it is evident, will correspond to the instant
at which the mitral or tricuspid valve, as the case may be, is closed,
and the second to the instant at which it is opened. And in like
manner, by comparing the pressure-curve of the aorta with that of
the left ventricle, the moment of opening and closure of the semi-
lunar valves may be determined (Figs. 33 and 34). According to the
best observations, the closure of the semilunar valves takes place at
a time corresponding to a point on the upper portion of the descend-
ing limb of the intraventricular curve.
On the blood-pressure curve of the aorta, simultaneously registered,
the corresponding point is near the bottom of the so-called ' aortic '
notch (p. 105) which precedes the dicrotic elevation. For clinical
purposes, in man the moment of closure of the semilunar valves
(denoted by the abbreviation S.C. point) may be taken as 0-03 second
before the bottom of the aortic notch in sphygmographic tracings
from the carotid, this being approximately the average time occupied
MECHANICS OF THE HEART-BEAT 97
by the pulse-wave in travelling from the aorta to the carotid. The
S.C. point, the A.O. point, or moment of opening of the auriculo-
ventricular valves, and the beginning of the ventricular systole, are
three important points of reference in the measurement and inter-
pretation of pulse-tracings in clinical work. The A.O. point in man
may be taken as a point ' 0-03 second in advance of the summit of
the dicrotic wave ' on the carotid pulse-tracing (Lewis). But this is
the most difficult of the three standard points to determine clinically
with anything like accuracy.
The study of the curves of endocardiac pressure enables us to add
precision in certain points to the description of the events of the
cardiac cycle which we have already given, and, as regards the
ventricles, to divide the cycle into four periods:
(1) A period dtiring which the pressure is lower in the ventricles than
either in the auricles or the arteries, and the auricula-ventricular valves
are consequently open, and the semilunar valves closed. This is the
period of ' filling ' of the heart, or the pause.
(2) A period, beginning with the ventricular systole, during which the
pressure is increasing abruptly in the ventricles, while they are as yet
completely cut off from the auricles on the one hand and the arteries on
the other by the closure of both sets of valves. This is the period of
' rising pressure, ' during which the ventricles are, so to say, ' getting up
steam.' The interval between the beginning of the ventricular systole
and the opening of the semilunar valves is termed the ' presphygmic '
interval.
(3) A period during which the pressure in the ventricles overtops that
in the arteries, and the semilunar valves are open, while the aiiriculo-
ventricular valves remain shut. This is the period of ' discharge ' or
' sphygmic ' period.
(4) A period during which the pressure in the ventricles is again less
than the arterial, while it still exceeds the auricular pressure, and both
sets of valves are closed. This is the period of rapid relaxation. The
interval between the closure of the semilunar and the opening of the
auriculo-ventricular valves is sometimes called the ' post-sphygmic '
interval.
Of the four periods, the second and fourth are exceedingly brief.
The third is relatively long and constant, being but slightly depen-
dent on either the pulse-rate or the pressure in the arteries. The
duration of the first period varies inversely as the frequency of the
heart ; with the ordinary pulse-rate it is the longest of all.
From records taken in a person with a defect in the chest-wall which
rendered the heart accessible the following results were obtained as
to the duration of the various events of the cardiac cycle : First and
fourth periods together, 0-445; third period, 0-254; second period (pre-
sphygmic interval), 0-051 second, the pulse-rate being 80 a minute
(Tigerstedt) . In another case with a similar defect the first period
lasted 0-32, the fourth period (post-sphygmic interval) 0-06, the second
and third periods together 0-4, and the auricular systole o-i second,
the pulse-rate being 66.
7
98
THE CIRCULATION OF THE BLOOD AND LYMPH
The Auricular (and Venous) Pressure-Curve. — The fluctuations of
pressure in the auricles, although confined within narrower limits
than in the ventricles, are of equal interest. They have been studied
in considerable detail both in animals and by indirect methods in
No fewer than three distinct elevations or ' positive waves,'
man.
separated or followed by three depressions or ' negative waves,'
have been described on the curve of intra-auricular pressure.
The first elevation corresponds to the systole of the auricle. The
second coincides with the onset of the ventricular systole, and is
Fig. 34. — Schematic Comparison of Pressure Curves in the Auricle (or Superior
Vena Cava), the Ventricle and the Aorta in the Dog (Fredericq). In the auricular
curve are to be distinguished ab, the first positive or presystolic wave, corre-
sponding to the auricular systole (a wave) ; bb' or be, second positive wave or
first systolic wave, which corresponds with the beginning of the ventricular
systole (c wave); b'cd, the steep negative wave of which the beginning corre-
sponds to the opening of the semilunar valves; def, the third positive wave
(v wave), more or less serrated, ending at/, the point of opening of the auriculo-
ventricular valves; fg, a negative wave corresponding to the relaxation of the
ventricle. The time is indicated along the abscissa in tenths of a second, the
pressure along the vertical axis at the left in mm. of mercury.
probably due to the sudden bulging of the auriculo- ventricular valve
into the auricle, or even to a slight regurgitation of blood from the
ventricle through the valve before it has completely closed. The
cause of the third elevation, which occurs during the period occupied
in the ventricular pressure-curve by the plateau, is less clearly made
out. In man, the events taking place in the right auricle during its
MECHANICS Of THE HEARTBEAT
systole can be followed to some extent by recording the venous pulse
in the jugular veins, especially the internal jugular, at the root of the
the neck (Fig. 36). Successful tracings can be obtained, not only in
certain pathological conditions, but in many normal individuals, and
it is probably only a matter of improved technique to obtain them
in all. The jugular venous pulse-tracing Ifop fhfr
If! " ""
Identical features are observed on records
of the normal venous pulse taken from veins
of dogs near the heart, and on records of the
pulse taken by a sound in the oesophagus.
The oesophagus pulse is related to the pul-
sation of the left auricle, the venous pulse to
the changes of pressure in the right auricle.
The first elevation, called the a (auricular)
or p (presystolic) wave, begins with, and is
the result of, the auricular systole. It is
probably produced by stasis in the veins due
to the contraction of the auricle, as well as
to the effect of the impact of the auricular
systole. The downstroke on the curve which
succeeds this first elevation corresponds to
the first negative wave or presystolic fall,
which is due to the auricular relaxation . Thi*
Fig- 35- — Schema of Events in the Cardiac Cycl«,
in Relation to the Venous Pulse (Ewing). i, Tracing
from Vena Cava, showing presystolic rise and fall,
PR, PF (a wave) ; SR, systolic rise and fall
(c wave); O', first onflow wave and, DR, diastolic
rise and fall (v wave); O*, second onflow wave;
2, auricular myogram (tracing of contraction of
auricle) ; 3, ventricular myogram (tracing of con-
traction of ventricle); 4, record of the movement
of the auriculo-ventricular septum; 5, ventricular
volume curve (plethysmographic curve of dis-
charge of the ventricles ) ; 6, curve of aortic pressure ;
7, intraventricular pressure-curve.
fall of pressure is terminated by a rise — the second positive wave — which
begins at the same moment as the ventricular systole, and is the ex-
pression on the venous pulse-curve of that second elevation of the
intra -auricular pressure whose probable cause has already been found
in the sharp protrusion of the auriculo-ventricular valve into the
auricular cavity under the stress of the ventricular systole while the
semilunar valve are still closed. In addition to the actual bulging of
the auriculo-ventricular valves, the impact of the sudden contraction
of the ventricle on its contents transmitted through the valve to
the contents of the auricle may aid in producing the rise of venous,
pressure. The second elevation has been termed the c wave by certain
too
THE CIRCULATION OF THE BLOOD AND LYMPH
writers, who studied it on jugular tracings, because they supposed it
to be simply transmitted from the pulse in the adjacent carotid artery.
This, however, has been shown to be erroneous, although it is true
enough that pulsations transmitted from the great arteries of the
thorax and neck may augment or distort the second elevation of the
venous pulse. It has been proposed that the second positive wave
should be called the s (systolic) wave. It lasts practically throughout
the presphygmic period of the ventricular systole ; the opening of the
semilunar valves, as indicated by the appearance of the pulse in the
innominate artery, occurs just before the end of the second elevation
(Porter, Ewing, etc.). The rapid discharge of the ventricle through the
open semilunar valves, and its consequent diminution in size, especially
in its longitudinal diameter, is associated with a dilatation of the
auricular cavity and a fall of intra- auricular pressure which is expressed
on the venous pulse -curve as the downstroke succeeding the second
positive wave. This second negative wave gives place to the third
positive wave, due to the steady inflow of blood into the auricle
from the veins. According to Ewing, the third positive wave, the v
Vs \\o\o Pulse
Fig. 36. — Normal Apex and Venous Pulses, Photographically Recorded (reduced
nine- tenths) (Niles and Wiggers). P, presystolic (or a) wave ; S, systolic (or c)
wave ; Dlf first diastolic (v) wave. In this venous record a second diastolic
wave, D2, is present. S1, vibrations corresponding to first sound ; S2, to second
sound.
wave of Mackenzie, really consists of two waves, the " first onflow
wave " and the " diastolic rise " or d wave. This last is terminated by
the third negative wave or diastolic fall of venous pressure coincident
with the opening of the auriculo-ventricular valves. The re-examina-
tion of the venous pulse with apparatus of which the moving parts
have an exceedingly small mass and optical methods of recording (see
p. 93) has confirmed the existence on the phlebogram of three essential
waves. A fourth is sometimes added when the cardiac cycle is long.
The first wave is clearly presystolic, the second systolic, as agreed by
all observers who have used polygraph tracings. The third wave,
however, is diastolic, as is, of course, the fourth when it exists. The
position of these waves can be definitely fixed by simultaneous heart
apex tracings, since on such optically recorded cardiograms the heart-
sounds are represented by distinct vibrations, except where the chest
wall is too thick or the heart overlaid by emphysematous lung. Some-
times heart-sound vibrations may be present also on the record of the
venous pulse (Wiggers).
MECHANICS OF THE CIRCULATION IN THE VESSELS 101
The jugular curve, when properly interpreted, affords valuable
information as to the action of the auricle, information of the same
kind as that afforded by the arterial pulse-tracing and the cardiogram
as to the action of the ventricle. In the in|^rprft°^on «•>*•'* he venous^
pulse-tracings, a simultaneous .record of the ja.rfia.1 or-Jae&er. the
carotid puls'eTor ofjJTg_^pex-beat--i£ always import aiit>^ajid^often
inj3rlpPn~n'hl'n. ?"r it^ryflhfp'i ; th? tilTIP nf nnSpt "f *^p wn?rTriilar
"ystol°jt£Lbg ^Rrk"^ "p^" *hp phlphngram (the venous trace), and
truTiacUitates the identification of the a wave, which must immedi-
ately precede, and the c or s wave, which should coincide with the
beginning of the contraction of the ventricle. The student must,
however, be warned that the proper interpretation of such tracings
in the study of cardiac disease is often difficult and requires special
knowledge and training.*
Suction Action of the Ventricle. — We have already said that a
negative pressure may be detected in the cardiac cavities by means of
a special form of mercurial manometer. This is confirmed by an
examination of the tracings written by good elastic manometers, for
the curves of both ventricles may often descend below the line of
atmospheric pressure. The cause of this negative pressure has been
much discussed. In part it may be ascribed to the aspiration of the
thoracic cage when it expands during inspiration (p. 226). But since
the pressure in a vigorously-beating heart may still become negative,
when the thorax has been opened, and the influence of the respiratory
movements eliminated, we must conclude that the recoil of the some-
what narrowed, or at least distorted, auriculo-ventricular rings, and of
elastic structures in the walls of the ventricles, exerts of itself a certain
suction upon the blood. This, however, is not an important factor in
the maintenance of the circulation.
SECTION III. — PHYSICAL OR MECHANICAL PHENOMENA OF THE
CIRCULATION IN THE BLOODVESSELS.
The Arterial Pulse. — At each contracton of the heart a quantity of
blood, probably varying within rather wide limits (p. 139). is forced
into the already full aorta. If the walls of the bloodvessels were
rigid, it is evident (p. 85) that exactly the same quantity would pass
at once from the veins into the right auricle. The work of the
ventricle would all be spent within the time of the systole, and only
while blood was being pumped out of the heart would any enter it.
Since, however, the vessels are extensible, some of the blood forced
into the aorta during the systole is heaped up in the arteries, beyond
which, in the narrow arterioles and in the capillary tract, with its
relatively great surface, the chief resistance lies. The arteries are
accordingly distended to a greater extent than before the systole,
and, being elastic, they keep contracting upon their contents until
the next systole over-distends them again. • In this way, during the
pause, the walls of the arteries are executing a kind of elastic systole,
* The necessary details must be sought in such works as Mackenzie's
Diseases of the Heart.'
loz THE CIRCULATION OF THE BLOOD AND LYMPH
and driving the blood on into the capillaries. The work done by the
ventricle is, in fact, partly stored up as potential energy in the tense
arterial wall, and this energy is being continually transformed into
work upon the blood during the pause, the heart continuing, as it
were, to contract by proxy during its diastole. Thus, the blood
progresses along the arteries in a series of waves, to which the name
of ' blood-waves ' or ' pulse-waves ' may be given. ^Wherever the
pulse-wave spreads it manifests itself in various ways — by an increase
of blood-pressure, an increase in the mean velocity of the blood-flow,
an increase in the volume of organs, and by the visible arrd palpable
signs to which the name of pulse is commonly given in a restricted
sense. The intermittence in the flow with which the pulse-wave is
necessarily associated is at its height at the beginning of the aorta.
In middle-sized arteries, such as the radial, it is still well marked, but
it dies away as the capillaries are reached, and only under special
conditions passes on into the veins, where, however, as has just been
mentioned, pulsatory phenomena of a different origin maybe detected.
The pulse was well known to the Greek physicians, and used by
them to a certain extent as an indication in practical medicine.
Harvey demonstrated with some clearness the relation of the pulse
to the contraction of the heart, but Thomas Young was the first to
form a proper conception of it as the outward token of a wave prop-
agated from heart to periphery.
When the finger is placed over a superficial artery like the carotid,
the radial, or the temporal, a throb or beat is felt, which, without
measurement, seems to be exactly coincident with the cardiac
impulse. In certain situations the pulse can be seen as a distinct
rhythmical rise and fall of the skin over the vessel. The throbbing
of the carotid, especially after exertion, is familiar to everyone, and
the beat of the ulnar artery can be easily rendered visible by extend-
ing the hand sharply on the wrist. When the pulse is felt by the
finger, it is not the expansion, but the hardening of the wall of the
vessel, due to the increase of arterial pressure, that is perceived ; and
even a superficial artery, when embedded in soft tissues so that it
cannot be compressed, gives no token of its presence to the sense of
touch. Sometimes an artery is longitudinally extended by the
pulse-wave, and this extension may be far more conspicuous than
the lateral dilatation. This is particularly seen when one point of
the vessel is fixed and a more distal point offers some obstruction to
the blood- flow, as at a bifurcation or in an artery which has been
ligatured and divided.
By means of the sphygmograph, the lateral movements of the
arterial wall, or, rather, in man, the movements of the skin and other
tissues lying over the bloodvessel, can be magnified and recorded.
It would be very unprofitable to enumerate all the sphygmographs
which ingenuity has invented and found names for. The first attempt
MECHANICS OF THE CIRCULATION IN THE VESSELS 103
Fig. 37. — Scheme of Marey's Sphygmo-
graph. A, toothed wheel connected with
axle H, and gearing into toothed upright
B; C, ivory pad which rests over blood-
vessel and is pressed on it by moving G,
a screw passing through the spring J ;
E, writing-lever attached to axle H, and
moved by its rotation. E writes on D, a
travelling surface moved by clockwork F.
to magnify the movements of the pulse was made by loosely attaching
a thin fibre of glass or wax to the skin with a little iard, in order to
demonstrate the venous pulse which appears under certain conditions.
In all modern sphygmographs there is a part, usually button-shaped,
which is pressed over the artery by means of a spring, as in Marey's
and Dudgeon's sphygmographs,
or by a weight, or by a column of
liquid. In Marey's instrument,
the button acts upon a toothed
rod gearing into a toothed wheel,
to which a lever, or a system of
levers, is attached. The lever has
a writing-point which records the
movement on a smoked plate, or
a plate covered with smoked
paper, drawn uniformly along by
clockwork (Figs. 37, 100). Special
forms of sphygmographs (poly-
graphs) have been devised, which,
by the addition of one or more
recording tambours, permit the
simultaneous record of movements from two or more points of the
vascular system — for example, the radial artery and the jugular vein,
or the radial or carotid artery, jugular vein, and the apex of the heart.
In rare cases, with de-
fect of the chest wall,
a tracing may be ob-
tained even from the
aorta (Fig. 40).
In a normal arterial
pulse-tracing (Fig. 38)
the ascent or ana-
erotic limb is abrupt
and unbroken ; the
descent or katacrotic
limb is more gradual,
and is interrupted by
one, two, or even
three or more, second-
ary wavelets. The
most important and
constant of these is
Fig. 38. — Pulse-Tracings, i, primary elevation ; 2, predi-
crotic or first tidal wave ; 3, dicrotic wave. The
depression between 2 and 3 is the dicrotic or aortic
notch ; 3 is better marked in B than in A. C, dicrotic
pulse with low arterial pressure; D, pulse with high
arterial pressure — summit of primary elevation in the
the one marked 3,
which has received the
name of the dicrotic
wave. Usually less
marked, and some-
times absent, is the
wavelet 2 between the dicrotic elevation and the apex of the curve.
It is generally termed the predicrotic wave. Oscillations, due to
vibrations of the recording apparatus, appear on many pulse-
form of an ascending plateau. E, systolic anacrotic
pulse; the secondary wavelet « occurs during the
upstroke corresponding to the ventricular systole.
F, presystolic anacrotic pulse; a occurs just before
the systole of the ventricle. In this rarer form of
anacrotism, a may sometimes be due to the auricular
systole when the aortic valves are incompetent.
io4
tracings, and it is important to recognize their cause, so that no
weight may be given to them.
In the explanation of the pulse-tracing, a fundamental fact to be
borne in mind is the elasticity of the vessels. When an incompres-
sible fluid like water is injected by an intermittent pump into one end
of an elastic tube a wave is set up, which is transmitted to the other
end of the tube. It is a positive wave — that
is, it causes an increase of pressure and an
expansion of the tube wherever it arrives;
and if a series of levers be placed in contact
with the tube, they will rise and sink in
succession as the wave passes them. After
the passage of this primary wave the walls of
the tube, instead of coming instantly to rest
in their original position, regain it by a series
of oscillations, first shrinking too much, then
expanding too much, but at each movement
coming nearer to the position of equilibrium.
Each vibration of the elastic wall is of course
accompanied by a change of pressure in the
contents of the tube. This change of pressure
runs along the tube as a wave; and such
waves, succeeding the primary one, may be
called secondary waves of oscillation. These
secondary waves will be set up in an elastic
system whether the distal end of the system
be closed or open. But if it is closed, or
sufficiently obstructed without being actu-
ally closed, secondary waves of another kind may also be generated,
the primary wave on arriving at the distal end being reflected there.
The reflected wave running back towards the central end may there
again undergo reflexion, and pass out once more towards the distal end
as a centrifugal, twice-reflected wave. When the liquid ceases to enter
the tube at the end of the stroke, a wave of diminished pressure — a
negative wave — is generated at the central
end, and is propagated to the distal end,
where it may be reflected just like the posi-
tive wave.
Although under certain conditions the
dicrotic wave is so marked that the double
beat of the pulse was discovered and
named by physicians long before the in-
vention of any sphygmograph, perhaps
no physiological question has been more
discussed or is less understood than the
mechanism of its production. Two
points, however, seem to be clear : (i) That
it is a centrifugal, and not a centripetal, wave — that is to say, it
travels away from, and not towards, the heart ; (2) that the aortic
semilunar valves have something to do with its origin.
It is not a centripetal wave, for in tracings taken at all parts of the
arterial path, no matter what the distance from the heart and the
Fig. 39. — Pulse - Tracings
from Different Arteries
(v. Frey). T, temporal;
R, radial ; P, artery of foot.
Fig. 40. — Pulse-Curve from
Human Aorta (after Tiger -
stedt).
MECHANICS OF THE CIRCULATION IN THE VESSELS 105
capillaries (e.g., the origin of the carotid and the radial at the wrist),
the dicrotic wave is separated by the same interval from the begin-
ning of the primary elevation. This can only be explained by
supposing that it has the same point of origin, and travels with the
same velocity and in the same direction as the primary wave. It is
not, then, a wave reflected directly from the peripheral distribution
of the artery from which the pulse-tracing is taken.
Some writers have contended that it is a centrifugal twice-reflected
wave, and, indeed, traces of such waves may be detected in the vessels
of newly-killed animals when changes of pressure of the same order
of magnitude as the arterial pulse are artificially produced by a pump
and recorded by elastic manometers connected with the interior of
an artery. It has been supposed that these secondary waves are
reflected first from peripheral points at which the blood-flow is particu-
larly obstructed (the bifurcations of the larger arteries, and the small
arteries and capillaries in general), and that, running towards the heart,
they are again reflected outwards from the semilunar valves. It has
been urged in support of this view that in very small animals (guinea-
pigs) no dicrotic elevation occurs on the pulse-tracing, since the path
which the reflected wave has to follow is so short that it arrives at the
root of the aorta before the primary elevation is over. But this
argument is by no means conclusive, and, indeed, the great difference
in the distance from the heart of the numerous points at which reflection
must take place is one of the chief difficulties of the hypothesis. For
it is not easy to understand how the reflected fragments of the primary
wave, arriving at different intervals at the heart, can be integrated into
the single considerable dicrotic elevation.
The explanation that best takes account of the facts and renders
most clear the role of the semilunar valves is somewhat as follows:
When the systole abruptly comes to an end and the outflow from the
ventricle ceases, the column of blood in the aorta tends still to move
on in virtue of its inertia, and a diminution of pressure, accom-
panied by a corresponding contraction of the aorta, takes place
behind it, just as a negative wave is set up in the central end of the
elastic tube when the stroke of the pump is over. At the same
moment, and while the semilunar valves are still for an instant in-
completely closed, the diminution of pressure in the beginning of the
aorta is intensified by the aspiration of the relaxing ventricle, which
sucks the blood back against the valves, and draws them a little way
into its cavity. A negative wave, therefore — a wave of diminished
pressure, represented in the pulse-curve by the ' aortic notch ' — •
travels out towards the periphery. The diminution of pressure is
quickly followed by a rebound, as always happens in an elastic
system. The recoiling blood meets the closed semilunar valves.
The aorta expands again, and the expansion is propagated once more
along the arteries as the dicrotic elevation. Lt is possible that this
elevation may be reinforced by a reflected wave produced in the
manner described.
io6 THE CIRCULATION OF THE BLOOD AND LYMPH
When the semilunar valve becomes incompetent in disease, or is
rendered insufficient in animals by the artificial rupture of one or
more of its segments, the dicrotic wave, as will be readily understood
from the manner in which it is produced, either disappears altogether
or is markedly enfeebled. But apart from any anatomical lesion or
functional defect in the aortic valves, the prominence of the wave
varies with a great number of circumstances, some of which are in a
measure understood, while others remain obscure. It varies in par-
ticular with the abruptness of discharge of the ventricle and the ex-
tensibility of the arteries. The conditions are usually favourable when
the arterial pressure is low, for the blood then passes quickly from the
ventricle into the arteries, which, already only moderately tense, are
easily dilated by the primary wave, then sharply collapse, and are again
abruptly distended when the dicrotic wave arrives. And, in fact, an
exaggeration of the dicrotic wavelet may be artificially produced by
nitrite of amyl (Fig. 102, p. 209), a drug which lessens the blood-pressure
by dilating the small arteries. Muscular exercise (Fig. 101, p. 209),
running or bicycling, for instance, has a similar effect on the sphygmo-
gram, although the explanation can scarcely be the same, since the blood-
pressure mounts rapidly when moderate exercise begins, and only
gradually falls during its continuance, with an abrupt decline to normal
or below it on cessation of work (Bowen). The increase in the pulse-
rate may have something to do in this case with the exaggeration of the
dicrotism, which is very frequently, although by no means invariably,
associated with a rapidly -beating heart, and therefore is often seen in
fever. On the other hand, in certain diseases associated with a high
arterial pressure, the dicrotic elevation almost disappears. Ather-
omatous arteries, being very inextensible, do not allow a dicrotic pulse.
Since the pulse represents a periodical increase and diminution in
the amount of distension of an artery at any point, the line joining
all the minima of the pulse-curve will vary in its height above the
base-line, or line of no pressure, according to the amount of permanent
distension, i.e., permanent blood-pressure, which the heart in any given
circumstances is able to maintain. Any circumstance that tends to
lessen the permanent distension will cause a fall of the line of minima,
and any circumstance tending to increase the distension will cause that
line to rise. If, for example, the arm be raised while a pulse-tracing
is being taken from the wrist, the line of minima falls because the
permanent pressure in the radial artery is diminished.
The form of the pulse-curve varies in the different arteries, and
therefore in making comparisons the same artery should be used.
When the wave of blood only enters an artery slowly, the ascending
part of the curve will be oblique. This is normally the case in a
pulse-curve of a distant artery, such as the posterior tibial. The
height of the wave is also less than in an artery nearer the heart, such
as the carotid, or even the axillary, where the primary elevation is
relatively abrupt (Fig. 39, p. 104).
Anacrotic Pulse. — As a rule, the ascent of the tracing is unbroken
by secondary waves, but in certain circumstances these may appear
on it. This condition, which, when well marked at any rate, may
be considered pathological, is called anacrotism (Fig. 38). It is seen
when the discharge of the left ventricle into the aorta is slow and
difficult — e.g., in cases where the orifice of the aorta has been
MECHANICS OF THE CIRCULATION IN THE VESSELS 107
narrowed from disease of the semilunar valves (aortic stenosis).
Since this condition is associated with hypertrophy and dilatation
of the left ventricle, the slow emptying of the ventricle is partly due
to the greater quantity of blood which it contains. In whatever
way the delay in the emptying of the ventricle is brought about, the
most probable explanation of the anacrotic pulse is that the delay
affords time for one or more secondary waves to be developed in the
arterial system before the summit of the curve has been reached, and
that these are superposed upon the long-drawn primary elevation.
In aortic insufficiency, where the left side of the heart is never cut off
entirely from the aorta, the auricular impulse is sometimes marked
on the pulse-curve as a distinct elevation; and this gives rise to a
peculiar kind of anacrotic pulse, especially in the arteries nearest the
heart (Fig. 38, F, p. 103).
Frequency of the Pulse. — In health, the working of the cardiac
pump is so smooth and apparently so self-directed that it needs a
certain degree of attention to perceive that the rate of the stroke is
not absolutely constant. It is, in reality, affected by many internal
conditions and external influences.
At the end of foetal life the rate is given as 144 to 133 ; from birth
till the end of the first year, 140 to 123 ; from 10 to 15 years, 91 to 76 ;
from 20 to 25 years, 73 to 69. It remains at this till 60 years, and
increases again somewhat in old age.* At all ages the pulse is some-
what quicker in the female than in the male, the excess amounting to
about 8 beats a minute. So that if we take the average rate for a
man (in the sitting position) as 72, the average for a woman will be
80. The difference is partly due to the fact that the average man
is taller than the average woman; and it is known that in persons of
the same sex and age the pulse-rate has an inverse relation to the
stature. But there may be, in addition, a real sexual difference.
It must not be forgotten that a certain number of perfectly healthy
persons, who may even be noted for their powers of physical en-
durance, have an habitually slow pulse, not above 50 in the minute.
The position of the body exercises a slight, but relatively constant,
influence on the rate, which is greater in the standing than in the
sitting posture, and greater in the latter than in the recumbent
position. And this is true even when muscular action is as far as
possible eliminated by fastening the person to a board. The pulse
* It must be remembered that these numbers are merely averages. Some
healthy individuals have a much lower pulse-rate than 72 per minute, and
some a rate considerably greater. Thus, while the average pulse-rate (taken
in the sitting position) of 87 healthy (male) students, whose ages ranged from
18 to 36 years, was 73, the extreme variation was from 54 to 89. In the
standing position the average was 80, and the variations 64 to 105. In
the supine position, average 69, and variations 48 to .98. After a short spell
of muscular exercise (generally running up and down some nights of stairs)
the average in the standing position was 119, the variations 75 to 164, and
the average increase 32.
lo8 THE CIRCULATION OF THE BLOOD AND LYMPH
is further affected by the respiratory movements, especially when
they are exaggerated in forced breathing, being accelerated during
each inspiration (p. 293). It is also increased by the taking of food,
and especially of alcoholic stimulants, by muscular exercise, in fever
and many other pathological conditions, and by a high external
temperature. A warm bath, for example, causes a very distinct
acceleration of the heart; and Delaroche found that in air at the
temperature of 65° C. his pulse went up to 160. A cold bath may
depress the pulse-rate to 60, or even less. During sleep it may fall
to 50. It is greatly influenced by psychical events, and that in the
direction either of an increase or a decrease. Finally, it ought to be
remembered as of some practical importance that the pulse-rate in
women and children, but particularly in the latter, is less steady
than in men, and more apt to be affected by trivial causes. And it
is a good general rule to let a short interval elapse after the finger is
laid on the artery before beginning to count the pulse, so that the
acceleration due to the agitation of the patient may have time to
subside.
Rate of Propagation of the Pulse-Wave. — When pulse-tracings are
taken simultaneously at two points of the arterial system unequally
distant from the heart, by two sphygmographs whose writing-points
move in the same vertical straight line, it is found that the ascent
of the curve begins later at the more distant than at the nearer point.
Since waves like the pulse-wave travel with approximately the same
velocity in different parts of an elastic system like the arterial ' tree,'
this ' delay ' must be due to the difference in the length of the two
paths. The difference in length can be measured; the time- value of
the ' delay ' can be deduced from the rate of movement of the re-
cording surface; dividing the length by the time, we arrive at the
rate of propagation of the pulse-wave. The average rate has been
found to be about 7 metres per second in man in the arteries of the
upper limb, and 8 metres in those of the lower limb, the difference
being due to the smaller distensibility of the latter. In sleep the
velocity diminishes almost a metre a second. It increases in arterio-
sclerosis, where the distensibility of the arteries is diminished, and
in chronic nephritis with hypertrophy of the heart, in which the
blood-pressure is increased. The mean velocity of the pulse-wave
is about the same as the speed of a moderately fast steamship (say,
17 miles an hour), but less than that of a wave of the sea in a strong
gale. The velocity of the pulse-wave must not be confounded with
that of the blood-stream itself, which is not one-thirtieth as great.
A ripple passes over the surface of a river at its own rate — a rate
that is independent of the velocity of the current. The passage of
the ripple is not a bodily transference of the particles of water of
which at any given moment the wave is composed, but the propaga-
tion of a change of relative position of the particles. The mere fact
MECHANICS OF THE CIRCULATION IN THE VESSELS 10$
that the ripple can pass upstream as well as down is sufficient to
illustrate this. The pulse-wave does not, however, correspond in
every respect to a ripple on a stream, for the bodily transfer of the
blood depends upon the series of blood-waves which the heart sets
travelling along the arteries. Every particle of blood is advanced,
on the whole, by a certain distance with every pulse-wave in which
for the time it takes its place. But no particle continues in the
front of the pulse- wave from beginning to end of the arterial system.
The ' delay ' or ' retardation ' of the pulse (the interval, say, between
the beginning of the ascent of the carotid and radial curves) is
practically constant in the same individual, not only in health, but
also in most diseases. But the retardation is markedly increased
when the pulse-wave has to pass through a portion of an artery
whose lumen is either greatly widened (in aneurism) or greatly
constricted (in endarteritis obliterans).
The Blood-Pressure Pulse in the Arteries. — In man it is only
possible to trace the pulse-wave along the arteries by movements of
the walls of the vessels transmitted through the overlying tissues.
In animals the changes of pressure that occu" in the blood itself can
be directly registered, and these changes may be spoken of as the
blood-pressure pulse. At bottom, as already pointed out, the
phenomenon is exactly the same as that we have been dealing with
in our study of the external pulse. We are only now to follow, by
a more direct, and in some respects a more perfect method, the same
wave of blood along the same channel.
Measurement of the Arterial Blood-Pressure. — Hales was the first to
measure the blood-pressure. This he did by connecting a tall glass
tube with the crural artery of a horse. The height to which the blood
rose in the tube indicated the pressure in the vessel. Poiseuille, nearly
half a century later, applied the mercury manometer, which had already
been used in physics, to the measurement of blood-pressure. Ludwig
and others improved this method by making the manometer self-
registering by means of a float in the open limb, supporting a style
which writes on a revolving drum, or kymograph. (For the method
of taking a blood-pressure tracing, see p. 210.)
For reasons already mentioned, the mercurial manometer is better
suited for measuring the mean blood -pressure, or for recording changes
in the pressure which last for some time, than for following the rapid
variations of the pulse -wave. For the latter purpose, one of the class
of elastic manometers is required (p. 93).
A blood-pressure tracing taken from an artery with a manometer
of this sort yields the truest picture of the pulse-wave which it is
possible to obtain, because the reproduction of it is the most direct.
The fact that such a tracing shows a close agreement with the trace
of a good sphygmograph properly applied to the corresponding artery
on the other side is a striking proof of the general accuracy of the
sphygmographic method for physiological purposes, and enables us to
guide ourselves in transferring to man, in whom, of course, the sphyg-
mograph can alone be used, the information derived from direct
manometric observations in
110
THE CIRCULATION OF THE BLOOD AND LYMPH
For the same reason it is unnecessary to discuss the manometric
tracings, as regards the pulsatory phenomena, in all their details.
It will be sufficient to say that, while the form of the blood-pressure
pulse-curve varies with the mean blood-pressure, the dicrotic wave
is always marked on it, preceded by one or more oscillations falling
within the period of the systole, and followed by one or more within
the period of the diastole. When the blood-pressure is low, the first
or primary elevation is the highest of the whole curve (Fig. 42). When
the blood-pressure is high, the maximum falls later coinciding with
one of the secondary
systolic waves, bux
always preceding the
dicrotic wave; and the
curve assumes an ana-
erotic character.
That all the secondary
oscillations, including the
dicrotic wavelet, are cen-
trifugal, and not centrip-
etal, may be shown, just
as in the sphygmographic
method, by recording the
blood -pressure simultane-
ously at two points of the
arterial system at differ-
ent distances from the
heart — e.g., in the crural
and carotid arteries. The
secondary waves are
found, by measuring the
tracings, to reach the
more distal point later
than the more central.
The increase of pres-
sure during the systole,
as indicated by the height
of the primary elevation,
is always very large, much
larger than it appears in a
tracing taken with a mer-
cury manometer. In the
rabbit this pulsatory variation is one -third to one -fourth of the minimum
pressure. In the dog it is still greater, owing to the slower rate of the
heart, and often amounts to 50 mm. of mercury, while under favourable
conditions (low minimum pressure and slowly - beating heart) the
systolic increase of pressure may be actually more than double the
minimum (Hiirthle). Pick found also, by means of his spring man-
ometer, that the pulsatory variations of blood-pressure were greater
than the respiratory variations (p. 289), although in the records of
the mercury manometer the reverse appears often to be the case.
Landois, too, in the course of experiments in which a divided artery
was allowed to spout against a moving surface, and to trace on it a
sort of pulse-curve painted in blood (a haemautogram as it is called),
Fig. 41.- — Arrangement for taking a Blood-Pressure
Tracing. M, manometer; Hg, mercury; F, float
armed with writing-point; A, thread attached to
a wire projecting from the drum and supporting
a small weight. The thread keeps the writing-
point in contact with the smoked paper on the
drum. B is a strong rubber tube connecting the
manometer with the artery; C, a pinchcock on
the rubber tube, which is taken off when a tracing
is to be obtained.
MECHANICS OP THE CIRCULATION IN THE VESSELS in
observed that the rate of escape of the blood was nearly 50 per cent,
greater during the systole than during the pause of the heart. The
existence of the dicrotic wave on this tracing was long looked on as the
best proof that it was not an artificial phenomenon.
The wave of increased pres-
sure, as it runs along the arterial
system, carries with it wherever
it arrives an increase of potential
energy. But this excess of po-
tential energy is continually being
worn down, owing to the friction
of the vascular bed ; and although
in the comparatively large arteries
the loss of energy is not great, it
rapidly increases as the arteries
approach their termination, and
begin to break up into the narrow
arterioles which feed the capillary
network. For not only is the ratio
of the total surface to the total
cross-section, and therefore the
friction, increased with every
bifurcation, but the mere change
of direction and division of the
wave cannot take place without
loss of energy. For this reason
the fluctuations of blood-pres-
sure are greater in the large arteries near the heart than in arteries
smaller and more remote. In the wide and much-branched capillary
bed the pulse-wave disappears altogether, and the blood-pressure
becomes relatively constant or permanent. And it is for some
purposes convenient to look upon
the blood-pressure in the arteries as
made up of a permanent element,
with pulsatory oscillations super-
posed on it. Since no portion of the
arterial system is more than partially
emptied in the interval between two
blood-waves, the minimum or per-
manent pressure is always positive
— i.e., always above that of the atmosphere, the beats of the heart
succeeding each other so rapidly that the successive waves over-
lap or ' interfere,' and are only separated at their crests.
If the heart is stopped while a blood-pressure tracing is being
taken— and we shall see later on how this can be done (p. 157) — the
minimum line of the tracing goes on falling towards the zero-line.
Fig. 42. — Curves of Blood-Pressure taken
with a Spring Manometer from the
Carotid Artery of a Dog (Hiirthle).
When i was taken the blood-pressure
was high; 2 corresponds to a medium,
3 to a low, and 4 to a very low, blood-
pressure; p is the primary elevation
— this and the succeeding elevations
between p and a are called systolic
waves; the systolic waves are followed
by a marked elevation d, which corre-
sponds to the dicrotic wave.
V v'W
Fig- 43- — Blood - Pressure Tracing.
The horizontal straight line inter-
secting the curves is the line of
mean pressure.
When .the heart begins beating again, the pressure-curve rises, not
by a continuous ascent, but by successive leaps, each corresponding
to a beat of the heart, and each overtopping its predecessor, till the
old line of minimum or of mean pressure is again reached.
The mean arterial blood-pressure is the permanent pressure plus
one-half of the average pulsatory oscillation. In a blood-pressure
tracing the line of permanent pressure joins all the minima; the line
of maximum pressure joins all the maxima ; the line of mean pressure
is drawn between them in such a way that, of the area included
between it and the blood-pressure curve, as much lies above as below
it (Fig. 43). As has been said, a tracing taken with a mercury man-
ometer gives approximately the mean blood-pressure. Each beat of
the heart is represented on it by a single elevation of variable size,
sometimes not amounting to more than one-twentieth of the height
of the curve above the line of zero or atmospheric pressure, but some-
times much larger. The oscillations due to the heart-beat are
superposed upon much longer, and often, as registered in this way,
larger waves, caused by the movements of respiration. So much
having been said by way of definition, we have now to consider the
amount of the mean arterial pressure, the variations which it under-
goes, and the factors on which its maintenance depends.
As to its amount, it will be sufficiently accurate to say that in the
systemic arteries of warm-blooded animals in general (including
birds), and of man in particular, the mean pressure does not, under
ordinary conditions, descend much below 100 mm. of mercury, nor
rise much above 200 mm. ; while in cold-blooded animals it seldom
exceeds 50 mm., and may fall as low as 20 mm.
It does not seem possible, at least with our present data, to further
subdivide these two great groups; nor do we know precisely whether
the distinction depends mainly on morphological or mainly on physio-
logical differences, whether, that is to say, the warm-blooded animal
has a higher blood-pressure than the cold-blooded chiefly because its
vascular system (and especially its heart) is anatomically more perfect.
or because its heart beats faster and works harder. It may be that
it is for both of these reasons that the birds, which in certain other
respects are more nearly related to the reptiles than to the mammals,
mount, as regards the pressure of the blood, into the mammalian class,
and that a manometer in the carotid of a goose will rise as high, or
almost as high, as in the carotid of a horse, a sheep, or a dog, while the
pressure in the aorta of a tortoise is no higher than in the aorta of a frog.
But we know that the mere average rate of the heart has of itself com-
paratively little influence on the blood-pressure within either group,
for the heart of a rabbit beats, on the average, very much faster than
the heart of a dog, and yet the arterial pressure in the dog is certainly
at least as great as in the rabbit. Nor does the size of the body seem
to have any definite relation to the mean pressure, even in animals
of the same species ; and there is no reason to suppose that the pressure
is materially less in the radial artery of a dwarf than in the radial artery
of a giant.
MECHANICS OF THE CIRCULATION IN THE VESSELS
Measurement of the Blood-Pressure in Man. — In man the blood-
pressure has been estimated by adjusting over an artery an instru-
ment known as a sphygmomanometer or sphygmometer, which, in
its most modern form, consists essentially of a hollow rubber pad or
bag containing air, and connected with a metallic pressure gauge or
a mercurial manometer.
The simplest method is that devised by Riva-Rocci (Fig. 44). An
armlet in the form of a broad rubber bag, supported externally by
canvas or leather, is adjusted round the upper arm. The interior of the
bag is connected with a mercury manometer, and also with a strong
rubber bulb provided with a valve. By rhythmical compression of
the bulb the pressure can be raised. Between the pressure bulb and
the rest of the system is a thin rubber balloon, which by its distension
renders the changes of pressure more gradual. The finger of the
observer is placed over the radial artery, ^nfl th*»
pressure is raised until the, pulse disappears. Then
the pressure is allowed to fall gradual! vT~ and the
manometer reading at the moment when the pulse
first reappears in the radial gives the maximum or
systolic pressure in the brachial artery.
Instead of palpating the radial artery, a stetho-
scope may be placed over the brachial just below
the edge of the armlet, according to the method of
Korotkoff , by which, in addition to the systolic, the
determined^ This is much the best of
all the methods of measuring the arterial
pressures in man. The pressure is
raised somewhat above that necessary
to obliterate the pulse, and then allowed
to fall slowly. At the moment when
pulsations first begin to break through
below the armlet, a succession of sharp
taps, synchronous with the pulse, is
heard. The tapping sound grows rapidly
louder as the artery opens up more and
more, then abruptly diminishes and
changes its character, and gradually dis-
appears. Several phases have been distinguished after the first maxi-
mum. Everybody agrees that the pressure shown by the manometer
thft gmmd is first heard is the svst<">1i>. jr^gg^r^ This corresponds
Fig. 44. — Riva-Rocci Apparatus.
a, armlet; b, manometer tube;
c, bottle containing mercury,
into which b dips ; d, thin
rubber bulb ; e, thick rubber
bulb for getting up pressure.
,
closely with the systolic pressure as determined by palpating the radial ;
and it can be shown experimentally that at pressures in the armlet
exceeding this the lumen of the brachial artery is actually obliterated
and not merely narrowed to such a degree as to prevent the passage of
the pulse wave, while still permitting the passage of some blood (see
Practical Exercises, p. 213).
The diastolic pressure is the, pressure at which a. sudden ^weakening
arm-firming ol the sound occurs (beginning of the fourth phase), and not
tne pressure at which the sound becomes altogether inaudible (Mac-
William, etc.). The sound seems to be due to vibrations set up in the
walls of the artery and the structures in con-tact with it, when it is
suddenly opened by the pulse waves. According to Erlanger, the essen-
tial thing is the ' water hammer ' action of the blood when, moving
through the artery under compression in the armlet, it strikes the stag-
nant blood in the uncompressed artery below and distends it.
THE CIRCULATION OF THE BLOOD AND LYMPH
Various instruments have been devised for determining the blood
pressure from the changes in the oscillations communicated to the arm-
let by the artery as the pressure in the armlet is allowed to fall or caused
to rise. The sphygmomanometer of Erlanger (Fig. 45) is arranged to
obtain graphic records of the pulse
from which both the maximum
and the minimum blood-pressures
may be deduced. The mean pres-
sure cannot be directly measured,
but must lie much nearer to the
minimum than to the maximum,
since the line of mean pressure bi-
sects the area enclosed by the
pulse curve, and this area is broad
at the base and narrow at the apex.
The rubber bag is applied in the
form of a cuff or armlet to the arm
above the elbow over the brachial
artery. It communicates with a
mercury manometer, which gives
the pressure exerted upon the arm.
It is also connected with a rubber
bulb, B, enclosed in
a glass bulb, G, and
through a stopcock
with a syringe bulb,
V, .provided with a
valve. ^The space
between" B and G
communicates (i)
with the tambour ;
(2) with the exterior
through the stopcock
by the tube E, and
also through a pin-
point opening in the
membrane of the
tambour. While the
armlet is
being ad-
justed the
stopcock is
* turned so
that the rubber bag is
in communication with
the external air through
F. The same is true of
the space TS in the
glass -bulb. The tam-
bour is thus protected
against undue strain during adjustment* The stopcock is now rotated
so as to cut off the armlet from the exterior and to permit the entrance
of air through F from V, which is used as a pump to raise the pressure,
the space TS and the tambour being still in communication with the
exterior. When the desired pressure has been reached, the stopcock
is turned into an intermediate position, which cuts off both the armlet
and the space TS from the exterior, and the pulse is then transmitted to
the tambour and recorded on the drum. By certain adjustments of the
Fig. 45. — Sphygmomanometer of Erlanger.
MECHANICS OF THE CIRCULATION IN THE VESSELS
115
stopcock air can be allowed to escape more or less rapidly from the
armlet.
To determine the maximum or systolic blood-pressure, the air-
pressure in the armlet is raised considerably (about 50 mm. Hg) above
what it is expected to be. While the lever is writing on the drum
the small oscillations due to the impact on the bag of the pulse-waves
in the central portion of the obliterated artery, the pressure is gradually
diminished by allowing air to escape. At the moment when the
pressure upon the arm falls below the maximum blood-pressure, and
the pulse-wave is first able to break through the brachial artery, the
oscillations of the lever will more or less abruptly increase in amplitude.
The pressure shown by the manometer at this point is the systolic
blood-pressure. To obtain the minimum or diastolic pressure, the air-
pressure in the armlet is raised somewhat (10 to 15 mm. Hg) above the
pressure expected. The pressure is diminished by 5 mm. Hg at a time,
records of the oscillations being taken on the drum. The manometer
reading at the point at which the oscillations, after reaching the maxi-
mum, begin abruptly to diminish, corresponds to the minimum blood-
pressure.
According to Brooks and Luckhardt, the criteria which are supposed
to fix the systolic and diastolic pressures in these and similar methods
yield results which are too high. The personal equation also seems to
introduce a considerable error in the selection of the points on the trac-
ings at which the characteristic changes are supposed to occur (Kilgore).
In using the sphygmometer of Hill and Barnard (Fig. 46), the bag
is inflated till the pulsation indicated by the gauge reaches a maxi-
mum. The mean
pressure shown
at this point is
assumed to be
equal to.or some-
what greater
than, the dia-
stolic pressure.
The effect of
muscular exer-
cise upon the
pressure is in-
fluenced by the
nature of the
work. Such an
effort as the lift-
ing of a heavy
weight causes
a sudden and
great increase,
which is very
transient. Thus,
the average arterial pressure in a number of men was in before,
1 80 during, and no two to three minutes after the lift (McCurdy). The
rise of pressure in this case is due largely to the marked diminution of
the calibre of the bloodvessels mechanically produced by the strong
and sustained contraction of the muscles. This increases the resistance
to the passage of the blood along the arteries, while the veins are emptied
by the pressure, and more blood thus reaches the right side of the heart.
It is obvious that the heart and vessels may easily be exposed to an
injurious strain during such efforts. In such an exercise as running,
while the pressure mounts to some extent at first, as already mentioned,
Fig. 46. — Sphygmometer of Hill and Barnard. It consists of
a broad armlet, A, connected by a T-tube, B, with a pressure
gauge, C, and a small compressing air-pump, D, fitted with
a valve.
u6 THE CIRCULATION OF THE BLOOD AND LYMPH
the rise is not maintained, owing to the dilatation of the cutaneous
vessels. In the anterior tibial artery of a boy whose leg was to be
amputated, the blood-pressure, measured by means of a manometer
connected directly with the artery, was found to vary from 100 to
1 60 mm., according to the position of the body and other circum-
stances. In a woman sixty years old, in good health, the following
readings were obtained with a sphygmomanometer :
June 28 - 126 — 130 mm. of mercury.
,, 29 ----- 126 — 136 „
Aug. 3 132 — 144
,,7 134— M0
„ 12 136 — 144
Such measurements on man show that the mean blood-pressure
under similar conditions in one and the same artery, and in one and
the same individual, may vary for a considerable time only within
comparatively narrow limits.
This relative constancy of the general arterial pressure is the
result of a delicate adjustment between the work of the heart, the
resistance of the vessels, and the volume of the circulating liquid.
The quantity of the blood is tolerably steady in health, and con-
siderable changes may be artificially produced in it (p. 191) without
affecting the pressure in any great degree. On the other hand, the
work of the heart and the peripheral resistance are highly variable
and vastly influential. A narrowing of the arterioles throughout
the body or in some extensive vascular tract increases the peripheral
resistance ; and if the heart continues to beat as before, the pressure
must rise. If the arterioles are widened, while the heart's action
remains unchanged, the pressure must fall. In like manner an
increase or a decrease in the activity of the heart, in the absence of any
change in the peripheral resistance, will cause a rise or a fall in the
blood-pressure. But if a slowing of the heart is accompanied by an
increase in the peripheral resistance, or a dilatation of the arterioles
by an increase in the activity of the heart, the one change may be
partially or completely balanced by the other, and the pressure may
vary within narrow limits or not at all.
Not only is the mean pressure, as measured in a large artery,
tolerably constant, but if recorded simultaneously in two arteries at
different distances from the heart, it is seen to decrease very gradu-
ally so long as the arteries remain large enough to hold a cannula.
It is nearly as high, for instance, in the crural artery of a dog as in
the carotid. It is easy to see that this must be so, for the resistance
of the arteries between the point where the arterioles are given off
and the heart is only a small fraction of the total resistance of the
vascular path; and we have said (p. 84) that the lateral pressure at
any cross-section of a system of tubes through which liquid is flow-
ing is proportional to the resistance still to be overcome. This is
also the reason why the pressure is always much lower in the pul-
monary artery and right ventricle than in the aorta and left ventricle
MECHANICS OF THE CIRCULATION IN THE VESSELS 117
(only one-fifth to one-sixth as great), for the total resistance of the
vascular path through the lungs is much less than that of the
systemic circuit. In dogs with natural respiration the pressure in
the pulmonary artery was found to vary between 14 and 26 mm. of
mercury, averaging about 20 mm.
The Velocity-Pulse. — We have seen that the blood is propelled
through the arteries in a series of waves that travel from the heart
towards the periphery. The particles in the front of the pulse-wave
are constantly changing, but since every section of the arterial tree
is successively distended, every section contains more blood while
the pulse-wave is passing over it than it contained immediately
before. And since there is always a fairly free passage for this blood
towards the periphery, there is a bodily transfer on the whole of a
certain quantity with every wave.
The translation of the blood, instead of being entirely intermittent,
as it would be in a rigid tube or in an elastic system with a slow
action of the central pump, is to some extent constantly going on ;
for a portion of a blood- wave is always passing through every section
of the arterial channel. Thus, we arrive at the same distinction as
to the onward movement of the blood itself as we previously reached
in regard to the blood-pressure, the distinction between the constant
or permanent factor of the velocity and the periodic factor, which
we may call the velocity-pulse.
The Velocity of the Blood. — By the velocity or rate of flow of a river
we should mean, if the flow were uniform throughout the whole cross-
section, the rate of movement of any given portion or particle of the
water. If we could identify a portion of the water, we could determine
the velocity by measuring the distance travelled over by that portion
in a given time. If the velocity was uniform over the channel, we could
predict the actual time which would be required to traverse any
fractional part of the measured distance. If, however, the velocity
of the current changed from point to point, then we could only deduce
from our observation the mean rate of the river for the measured dis-
tance. To determine the actual rate for any given portion of this
distance over which the rate was uniform, we should have to make a
separate observation for this portion alone.
But as soon as we pass from an ideal frictionless river to an actual
stream, in which the water at the bottom and near the banks flows
more slowly than that in the middle and on the surface, we are in every
case restricted to the notion of mean velocity. We may distinguish
between the velocity of different parts of the current, between that of
the mid-stream and the side current, the bottom and the surface layers ;
but when we consider the river as a whole, we take cognizance only
of the mean or average velocity. And at any cross-section this may
be defined as the volume of water passing per hour, or whatever the
unit of time may be, divided by the cross-section of the current. It is
evident that this does not enable us to determine the actual velocity
of any given particle of the water at any given moment within a
measured interval ; nor does it tell us whether or not the average velocity
of the current has itself undergone variations within the period of
observation.
n8
We have dwelt upon this point because the measurement of the
velocity of the blood, to which we must now turn, involves the same
considerations. Within the smaller arteries, as the microscope
shows us, and as we should in any case expect from what we know
of fluid motion, the blood-current, apart from the periodical varia-
tions in its velocity, due to the action of the heart, varies in speed
from point to point of the same cross-section. The layer next the
periphery of the vessel, the so-called peripheral plasma-layer or
Poiseuille's space, moves more slowly than the central portion, the
axial stream. In fact, we must suppose that in the large as well as
in the small vessels the layer just in contact with the vessel-wall is
at rest, while the stratum internal to this slides on it and has its
velocity diminished by the friction. The next layer again slides on
the last, but since this is already in motion, its velocity is not so
much diminished, and so on. The velocity must therefore increase
as we pass towards the axis of the bloodvessel, and reach its maxi-
mum there (p. 193).
Again, the velocity must be altered wherever an alteration occurs
in the width of the bed, that is, in the total cross-section of the
vascular system ; for since as much blood comes back in a given time
to the right side of the heart as leaves the left side, the same quantity
must pass in a given time through every cross-section of the circula-
tion. Wherever the total section of the vascular tree increases, the
blood-current must slacken; wherever it diminishes, the current
must become more rapid. Now, the total section, increasing some-
what as we pass from the heart along the branching arteries, under-
goes an abrupt augmentation, and reaches its maximum in the
capillary region. It suddenly diminishes again at the venous end
of the capillary tract, and then more gradually as we pass heart-
wards along the veins, but never becomes so small as in the arterial
tract. We must, therefore, expect the mean velocity to be greatfig*
in the large arteries, less in the veins, and least in the arterioles,
capillaries, and venules. It must, of course, be remembered that the
total section varies from time to time at any given distance from the
heart. The capillary tract is especially variable in its area, and
capillaries full of blood at one moment may be collapsed and empty
at another, according to the changes of calibre and pressure in the
arteries which feed and the veins which drain them.
Although in strictness we are only at present concerned with the
arteries, it will be well to consider here what a change of velocity at
any part of the vascular channel really implies. To say that when
the channel widens the velocity diminishes is not to explain the
meaning of this diminution. A diminution of velocity implies a
diminution of kinetic energy, and it is necessary to know what becomes
of the energy that disappears. The stock of energy imparted by the
contraction of the heart to a given mass of blood constantly diminishes
as it passes round from the aorta to the right side of the heart, for
friction is constantly being overcome and heat generated. This energy,
ng
as we have seen, exists in a moving liquid in two forms, potential and
kinetic, the former being measured by the lateral pressure, the latter
varying directly as the square of the velocity. Whenever the velocity,
and therefore the kinetic energy, of a given mass of the blood is
diminished without a corresponding increase in the potential energy,
some of the total stock of energy must have been used up to overcome
resistance (p. 84).
In a uniform, rigid, horizontal tube, as has been already remarked,
the velocity (and consequently the kinetic energy) is the same at
every cross-section of the tube, while the potential energy, represented
by the lateral pressure, diminishes regularly along the tube. When
the calibre of the tube varies, it is different. Suppose, for instance,
that the liquid passes from a narrower to a wider part, the velocity
must diminish in the latter. The kinetic energy of visible motion
which has disappeared must have left something in its room. Here
there are three possibilities: (i) The kinetic energy that has disappeared
may be just enough to overcome the extra friction in the wider part of
the tube due to eddies and consequent change of direction of the lines
of flow; in this case the potential energy of a given mass of the liquid
will be the same at the beginning of the wider part as in the narrower
part. The lost kinetic energy will have been transformed into heat.
(2) The kinetic energy which has disappeared may be greater than is
enough to overcome the extra resistance ; a portion of it must, therefore,
have gone to increase the potential energy, and the lateral pressure will
be greater in the wide than in the narrow part. (3) The lost kinetic
energy may be less than enough to overcome the extra resistance; in
this case both the lateral pressure and the velocity will be less in the
wide than in the narrow part. It has been experimentally shown that
when a narrow portion of a tube is succeeded by a considerably wider
portion, and this again by a narrow part, case (2) holds; and the liquid
may, under these conditions, actually flow from a place of lower to a
place of higher lateral pressure.
In the vascular system the conditions are not the same. The
widening of the bed which takes place as we proceed in the direction
of the arterial current is not due to the widening of a single trunk,
but to the branching of the channel into smaller and smaller tubes.
In the larger arteries the increase of resistance is so gradual that both
the potential and the kinetic energy diminish only slowly, and the
lateral pressure and velocity are not much less in the femoral artery
than in the aorta or carotid. But in the arterioles the friction
increases so greatly that although the velocity, and therefore the
kinetic energy, in the capillary region is much less than in the
arteries, the amount of kinetic energy lost is not upon the whole
equivalent to the energy consumed in overcoming the extra resis-
tance; the potential energy of the blood is also drawn upon, and the
lateral pr.essure falls sharply in the capillary region, as well as the
velocity. Where the capillaries open into the veins, the lateral pres-
sure again sinks abruptly, while the velocity begins to increase, till in
the largest veins it is probably about half as great as in the aorta.
Where does the extra kinetic energy of the blood in the veins come
from ? To say that the vascular channel again contracts as the
blood passes from the capillaries into the veins, and that, since the
120 THE CIRCULATION OF THE BLOOD AND LYMPH
same quantity must flow through every cross-section of the channel,
the velocity must necessarily be greater in the narrower than in the
wider part, does not answer the question. The greater portion of
the kinetic energy of the arterial blood is, as we have seen, destroyed,
or, rather, changed into an unavailable form, into heat, in the capil-
lary region. The mean velocity of the blood in the capillaries is not
more than -g-^ to ;I^ of the velocity in the aorta; the kinetic energy
of a given mass of blood in the capillaries cannot therefore be more
than (-2-5T7)2, or 4 0 * 0 0 of its kinetic energy in the aorta. In the veins,
taking the velocity at half the arterial velocity, the kinetic energy
of the mass would be one-fourth of that in the aorta, or at least
10,000 times as great as in the capillary region. This extra kinetic,
energy comes partly from the transformation of some of the poten-
tial energy of the blood. The resistance in the veins is very small
compared with that in the capillaries; less of the potential energy
represented by the lateral pressure at the end of the capillary tract
is required to overcome this resistance, and some of it is converted
into the kinetic energy of visible motion, the lateral pressure at the
same time falling somewhat abruptly. Contributory sources of
kinetic energy in the veins are the aspiration caused by the respira-
tory movements and the pressure caused by muscular contraction
in general, which, thanks to the valves, always aids the flow towards
the heart. From these two sources new energy is supplied, to rein-
force the remnant due to the cardiac systole (p. 133).
Measurement of the Velocity of the Blood — i . Direct Observation. —
(a) This method can be applied to transparent parts by observing the
rate of flow of the corpuscles under the microscope. But it is only
where the blood moves slowly, as in the capillaries, that the method
is of use. (6) Part of the path of the blood through a large vessel may
be artificially rendered transparent by the introduction of a glass tube,
of approximately the same bore as the vessel (Volkmann). The tube
is filled with salt solution, and the blood admitted by means of a stop-
cock at the moment of observation. The time which the blood takes
to pass from one end of the tube to the other is noted, and the length
divided by the time gives the velocity of the blood in the tube. If the
calibre of the tube is the same as that of the artery, this is also the
velocity in the vessel ; but if the calibre is different, a correction would
have to be made. The method is not a good one, for the reason, among
others, that the long tube introduces an extra resistance.
2. Ludwig's Stromuhr. — This instrument measures the quantity of
blood which passes in a given time through the vessel at the cross-
section where it is inserted. It consists of a U-shaped tube, with the
limbs widened into bulbs, but narrow at the free ends, which are con-
nected with a metal disc. By rotating the instrument, these ends
can be placed alternately in communication with a cannula in the
central, and another in the peripheral, portion of a divided artery;
or they can be placed so that none of the blood passes through the bulbs,
but all goes by a short-cut. One limb of the instrument is filled with
oil, and the other with defibrinated blood. The limb containing the
oil is first put into communication with the central end, and that con-
taining the blood with the peripheral end, of the artery. The blood
MECHANICS OF THE CIRCULATION IN THE VESSELS 121
from the artery rushes in and displaces the oil into the other limb, the
defibrinated blood passing on into the circulation. As soon as the blood
has reached a certain height, indicated by a mark, the instrument is
reversed and the oil is again displaced into the limb it originally
occupied. This process is repeated again and again, the time from
beginning to end of an experiment being
carefully noted. The number of times
the blood has filled a bulb in that
period, the capacity of the bulb and the
cross-section of the vessel being known,
all the data required for calculating the
velocity of the blood in the vessel have
been obtained.
Suppose, for example, that the cap-
acity of the bulb up to the mark is 5 c.c.,
and that it is filled twelve times in a
minute, the quantity flowing through
the cross-section of the artery is I c.c.,
or 1,000 cub. mm., per second. Let the
diameter of the vessel be 3 mm., then its
sectional area is re x (- \ =— — -=7-06
sq. mm. The velocity is
-- ^
= 11 mm
Fig. 47.— StromuhrofLudwigand
Dogiel. A, B, glass bulbs; a, a
metal disc, to which A and G
are attached, and which can be
rotated on the disc 6 ; E, F, can-
nulae attached to b, and con-
nected with the peripheral and
central ends of a divided blood-
vessel. At the beginning of the
experiment, A and the junction
between A and B are filled with
oil; B is filled with physiological
salt solution or defibrinated
blood: a being turned into the
position shown in the figure, the
blood passes through F and D
into A , and the oil is forced into
JB. As soon as the blood has
reached the mark m, the disc a,
with the bulbs, is rapidly ro-
tated, so that C is now opposite
F. The blood now passes into
B, and the oil is again driven
into A. When the oil has
reached D, reversal is again
made, and so on.
per second.
Various improvements in this method
have been made, such as a graphic regis-
tration of the reversals of the stromuhr.
3. A tube or box, in which swings a
small pendulum, is inserted in the course
Fig. 48.— Pitot's Tubes.
of the vessel. The pendulum is deflected
by the blood, and the amount of the
deflection bears a relation to the ve-
locity of the stream (Vierordt's hczmatachometer ; Chauveau and Lortet's
much more perfect dromograph) (Fig. 49).
4. Pilot's Tubes. — If two vertical tubes, a and b, of the form shown in
Fig. 48, be inserted into a horizontal tube in which liquid is flowing hi
the direction of the arrow, the level will be higher in a than would be
the case in an ordinary side-tube without an elbow ; in b it will be lower.
For the moving liquid will exert a push on the column in a, and a pull
122
THE CIRCULATION OF THE BLOOD AND LYMPH
on that in b. The amount of this push and pull will vary with the
velocity, so that a change in the latter will correspond to an alteration
in the difference of level in the two tubes. Instruments on this prin-
ciple have been constructed by Marey and Cybulski, the former regis-
tering the movements of the two columns of blood by connecting the
tubes to tambours provided with writing levers, the latter by photo-
graphy (Fig. 50).
5. The electrical method, described on p. 135,
for the measurement of the circulation time, can
also be applied to the estimation of the mean
velocity of the blood between two cross-sections
of the arterial path which are separated by a
sufficient distance. For example, salt solution
can be injected into the left ventricle or the be-
ginning of the aorta, and the interval which it
takes to reach a pair of electrodes in contact with,
say, the femoral artery determined. Knowing
the distance between the point of injection and
the electrodes, we can then calculate the mean
velocity.
6. In the calorimetnc method of measuring the
quantity of blood which passes through such
parts as the hands (or feet) in man, the flow is
deduced from the quantity of heat given off by
the part in a given time, and the difference be-
tween the temperatures of the blood entering and
leaving the part. The hands are immersed in a
large bath of water (a few degrees below arterial
blood temperature) for a sufficient time to permit
any change of temperature of the parts due to
the difference in temperature between them and
the water to be established. The hands are then
rapidly transferred to calorimeters previously
filled with water at the same temperature as that
of the bath. All the heat henceforth given off
can be assumed to be due to the cooling of the
blood passing through the hands, since the small
amount of heat produced in the resting hands is
negligible for this purpose. The temperature of
the arterial blood at the wrist is taken as 0-5° C.
below that of the rectum, this being the relation
actually found in a normal man.* The tempera-
ture of the venous blood leaving the hand is taken
as that of the calorimeter, since it has been found
that blood withdrawn from the hand veins by
puncture, and collected with suitable precautions
to prevent loss of heat as far as possible and to
permit the calculation of the unavoidable loss,
has a temperature only a negligible fraction
of a degree above that of the bath in which the hand is im-
mersed. The flow in grammes per minute is obtained from the formula
Q= — rr — THV ~> where Q is the quantity of blood, H the number
Wl \\- J. j S
* The temperature of the arterial blood at the wrist was assumed to be the
calorimeter temperature at which the calorimeter neither loses heat to the hand
nor g-uns heat from it. If the heat production in the resting hand is negligible,
this must correspond to the temperature of the entering blood.
Fig. 49. — Chauveau's
Dromograph. A, tube
connected with blood-
vessel; B, metal cylin-
der in communica-
tion with A. The upper
end of B has a hole in
the centre, which is
covered by a mem-
brane, m, through
which a lever, C,
passes; C has a small
disc, p, at its end,
which projects into the
lumen of A, and is de-
flected in the direction
of the blood - stream
through A. The de-
flection is registered by
a recording tambour in
communication by the
tube E with a tambour
D, the flexible mem-
brane of which is con-
nected with the lever
or pendulum C.
MECHANICS OF THE CIRCULATION IN THE VESSELS 123
of small calories (gramme-calories) given off in m minutes, T the tem-
perature of the blood entering the hand, T1 the temperature of the
blood leaving the hand, and s the specific heat of blood (0-9). For
purposes of comparison the volume of the hands is measured, and the
blood-flow expressed in grammes per 100 c.c. of hand per minute.
Further details are given in the Practical Exercises (p. 219). Fig. 51
shows one of the calorimeters on its adjustable stand. The collar of
thick felt which fits closely around the wrist, and prevents loss of heat
from the orifice through which the hand is
inserted, is shown standing on the top of
the calorimeter, as also the thermometer
with the small sliding lens, or ' reader.' In
Fig. 108, p. 220, the position of the subject
with hands in the calorimeters is shown.
Fig- 50- — Cybulski's Arrangement for recording
Variation's in the Velocity of the Blood. A, tube
connected with central, B with peripheral, end
of divided bloodvessel. The blood stands higher
in the tube C than in D. A beam of light passing
through the meniscus in both tubes is focussed by
the lens L on the travelling photographic plate E.
The velocity at any moment is deduced from the
height of the meniscus in the two tubes C and D.
Fig. 51. — Calorimeter with
stand for measuring
blood-flow in hand.
Of these methods, 3 and 4 are alone suited for the study of the
velocity-pulse, that is, the change of velocity occurring with every
beat of the heart. The curves obtanied by Chauveau's dromo-
graph show a general agreement with blood-pressure tracings taken
by a spring manometer, and with records of the external pulse
obtained by a sphygmograph. There is a primary increase of
velocity corresponding with the ventricular systole, and a secondary
increase corresponding with the dicrotic wave (Fig. 54). Like all
the other pulsatory phenomena, the velocity- pulse disappears in the
capillaries, and is only present under exceptional circumstances in
the veins.
1 24 THE CIRCULATION OF THE BLOOD AND LYMPH
Fick, from a comparison of sphygmographic and plethysmographic
tracings (p. 128), taken simultaneously from the radial artery and
the hand, has demonstrated that in man the velocity-pulse exhibits
Fig. 52. Fig. 53-
Fig. 52. — The highest of the three curves is a plethysmographic record taken from
the hand; the second curve is a sphygmogram taken simultaneously from the
corresponding radial artery; the lowest (interrupted) curve is the curve of velocity
deduced from a comparison of the first two (Fick).
Fig- 53. — Simultaneous plethysmographic and sphygmographic tracings.
the same general characters as in animals (Figs. 52 and 53). And
v. Kries has confirmed Fick's conclusions by actual records .of the
velocity-pulse obtained by means of an arrangement called a gas
tachograph (Fig. 55).
Fig. 54. — Simultaneous Tracings of the Velocity (Upper Curve) and Pressure (Lower
Curve) (Lortet). The tracings were taken from the carotid artery of a horse.
The curve of velocity was obtained by the dromograph. The dicrotic wavs is
marked on it. The slightly curved ordinates drawn through the curves indicate
corresponding points.
This consists of a plethysmograph connected with the tube of a gas-
burner. When the part enclosed in the plethysmograph expands, air
issues from the connecting tube, and causes an increase in the height of
the flame. When the part shrinks, air is drawn in from the flame,
which is depressed. Since the speed of the blood in the veins may be
considered constant during the time of an experiment, the rate at which
MECHANICS OF THE' CIRCULATION IN THE VESSELS 125
the volume of the part alters at any moment is a measure of the pulsa-
tory change of velocity in the arteries of the part. And by photo-
graphing the movements of the flame on a travelling sensitive surface,
the velocity-pulse is directly recorded.
The mean velocity, like the mean blood-pressure, is more variable
in the large arteries near the heart than in the smaller and more
di stant arteries.
Dogiel found in
measurements
taken with the
stromuhr (a good
instrument for the
estimation of mean
speed), within a
period of two
minutes, velocities
ranging from over
200 mm. to under
100 mm. per second
in the carotid of the
rabbit, and from over 500 mm. to less than 250 mm. in the carotid of
the dog. Chauveau, with the dromograph, found the velocity in the
carotid of a horse to be 520 mm. per second during systole, 150 mm.
during the pause, 220 mm. during the period of the dicrotic wave.
It is probable, however, that, if these numbers are at all accurate
for bloodvessels in the immediate neighbourhood of the heart, there
must be a rapid diminution in the velocity even while the arteries
are still of considerable calibre. For it has been found . by the
electrical method that, in anaesthetized dogs at any rate, as is shown
in the following table, the mean velocity between the origin of the
aorta and the crural artery in the middle of the thigh is usually less
than 100 mm. per second.
Fig- 55- — Photographic Record of the Velocity-Pulse ob-
tained by the Gas Tachograph (v. Kries). The upper
curve is the photographic representation of the move-
ments of the flame, and corresponds to the curve of
velocity.
No. of
Experi-
ment.
Body,
weight
in Kilos.
Distance
between Point
of Injection and
Electrodes,
in Millimetres.
Average Time be-
tween Injection
and Arrival of the
Salt Solution, in
Seconds.
Average
Pulse-rate
per Minute.
Average
Velocity
per
Second,
in Milli-
Average
Distance
traversed per
Heart-beat,
in Milli-
I.
34'55
42O
4 '62
105
90-9
51-9
II.
17-5
495
57
69
86«8
75*4
III.
14-99
400
5'0
102
80-0
47-0
IV.
10-32
470
7-12
74-5
72-9
58-7
V.
7-165
330
7-83
46-3
42-1
54'5
(weak beat)
i
In I. the injecting cannula was in the descending part of the thoracic
aorta, in V. at the very origin of the aorta, and in II., III., and IV.
in the left ventricle.
126
THE CIRCULATION OF THE BLOOD AND LYMPH
As to the speed of the blood in the arteries of man, our data are
insufficient for more than a loose estimate. But it does not seem
likely that the mean velocity of a particle of blood in moving from
the heart to the femoral artery can exceed 150 mm. per second for
the whole of its path. This would correspond to rather more than
a third of a mile per hour. In the arch of the aorta the average
speed may be twice as great. ' The rivers of the blood ' are, even
at their fastest, no more rapid than a sluggish stream. A red cor-
puscle, even if it continued to move with the velocity with which it
set out through the aorta, would only cover about 15 miles in twenty-
four hours, and would require five years to go round the world.
The average flow through the hands of a healthy young man, as
determined in eighteen experiments on different dates ranging over
two years, at room temperatures varying from 19° to 27° C., was
12-8 grammes per 100 c.c. of hand per minute for the right hand, and
12-3 grammes for the left. Ten of the observations on this man are con-
densed in the table.
Blood-flow in Grammes
Temperature of—-
per 100 c.c. of Hand
per Minute.
Date.
Room. '
Arterial
Blood.
Calorim.
Right
Left.
November 30, 1910 -
20-2
36-6
28-0
I0'l
9'4
December 22, 1910 -
2I-I
36'8
29-7
I3'7
12-5
February I, 1911
22-8
36-9
30-3
12-6
12-7
March 17, 1911
2I-I
36-6
29-9
n-8
n-3
May 24, 1911 -
27-0
36-8
30-9
18-5
17-5
November 3, 1911 -
25-I
36-7
30-0
I2-I
n-7
November 9, 1911 -
24-I
36-7
30-8
IS'?
12-5
November 15, 1911 -
25-2
36-8
30-8
I4'O
13-8
December n, 1911 -
24-5
36-6
3I-I
12-4
12 '0
March 26, 1913
24-5
36-6
31'5
14-7
I5'I
Since the great function of the circulation in the skin is the regulation
of the temperature of the body (see Chapter XII.), the blood-flow in
the hands is, of course, much influenced by the external temperature.
Thus, by far the greatest flow in the above table corresponds to the
high room temperature of 27° C. With a given external temperature,
the degree of humidity of the air also affects the flow. Under similar
conditions of external temperature and daily routine, including diet,
the hand flow in one and the same individual does not vary greatly
when measured at about the same hour on different days. Different
individuals, when tested under apparently similar conditions, show a
greater range in the blood-flow. Some normal persons know and say
that their hands are habitually cool or cold; others, like the man on
whom the above results were obtained, that their hands are habitually
warm. The former may be expected to show a relatively small, and
the latter a relatively large, flow of blood through the hands. It is
MECHANICS OF THE CIRCULATION IN THE VESSELS 127
possible that such habitual differences are associated with differences
in the total heat value of the food consumed or in the proportions of
the various food substances, especially of proteins (see p. 605),
for it is well known that even persons engaged in the same work, and
living under similar external conditions, may differ greatly in their
dietetic habits, both as to quantity and quality of the food. And since
the cutaneous circulation is by far the most important factor in the
loss of heat from the body, the hearty eaters, other things being equal,
may be expected to have the largest blood-flow through parts like the
hands. The importance of the flow through the skin in the total hand
flow is illustrated by the fact that the flow per unit of volume through
the distal half of the hand, which, of course, has a large surface in
proportion to its volume, is considerably greater than through the hand
as a whole. For the forearm the flow per 100 c.c. is, in its turn, much
less than in the hand (Hewlett) . In the foot the blood-flow, as estimated
by the calorimetric method, is smaller per unit of volume of the part
than in the hand, the ratio of foot flow to hand flow per 100 c.c. of the
part usually lying in normal persons between i to 3 and i to 2. This
is largely due to the proportionally greater proportion of skin in the
hand, as well as to the smaller proportion of bone, which has not an
active circulation. In the sitting position the following results were
obtained for the flow in the feet on the person whose hand flows have
been given above :
Blood-flow in Grammes
Temperature of—
per 100 c.c. of Foot
per Minute.
Date.
Room.
Arterial
Blood.
Calorim.i
Right.
Left
May 2, 1911 -
25-2
36-8
30-4
3'5
^_
May 18, 1911 - •
26-4
36-9
31'4
3'5
—
June 17,1911 -
21-8
37-o
30-6
4'9
4*2
March 26, 1913
24-5
36-5
31-4
3'9
4-1
The great variations in the vascularity of different organs and parts,
as revealed by the examination of injected specimens or by inspection
of the organs during life, indicate that there must be great differences
in the blood-flow. Observations with the stromuhr in animals have
shown that this is the case. The following list gives the number of
c.c. of blood passing per minute through 100 grammes of organ, according
to the results of Burton-Opitz, Tigerstedt, and other observers :
Posterior extremity. « 5 Liver (venous) . 59
Skeletal muscle „ . 12 Liver (total) . . .84
Head .... 20 Brain . . ... . 136
Stomach .. 21 Kidney .. . 150
Liver (arterial) > 25 Adrenal . . . 500
Intestines . . 31 Thyroid gland . 560
Spleen ..» 58
The Volume-Pulse. — When the pulse-wave reaches a part it dis-
tends its arteries, increases its volume, and gives" rise to what may
be called the volume-pulse.
128
THE CIRCULATION OF THE BLOOD AND LYMPH
This may be readily recorded by means of a pie thy s mo graph, an
instrument consisting essentially of a chamber with rigid walls which
enclose the organ, the intervening space being filled up with liquid
(Fig. 56). The hiovements of the liquid are transmitted either through
a tube filled with air to a recording tambour, or directly to a piston or
float acting upon a writing lever. Special names have been given to
plethysmographs adapted to particular organs; for example, Roy's
oncometer for the kidney. The method has been successfully applied
to the investigation of circulatory changes in man, a finger, a hand or
an entire limb being enclosed in the plethysmo graph. With a fairly
sensitive arrangement, every beat of the heart is represented on the
tracing by a primary elevation and a dicrotic wave (Fig. 57).
The general appearance of the
curve is very similar to that of an
ordinary pulse-tracing, though
there are some differences of detail,
especially in the time relations. A
volume-pulse has been actually ob-
served not only in limbs and por-
tions of limbs, but also (in animals)
in the spleen, kidney and brain
and other organs, and in the orbit.
Fig. 56. — Plethysmograph (Mosso). M, balanced test-tube, in communication with
the glass vessel, D, which contains the arm, escape of water being prevented by
the rubber cuff, A . When water passes from vessel D to M , or from M to D,
M moves down or up, and its movements are recorded by the writing-point .V.
M is steadied by the liquid in P, into which it dips.
The so-called cardio-pneumatic movements also constitute a
volume-pulse, although of complex origin. This name is given to
the rhythmical changes of pressure accompanying the beat of the
heart, which can be detected in the air of the respiratory passages
when one nostril is connected with a recording tambour, or water
manometer, the other nostril and the mouth being closed, and the
respiration suspended in inspiration, with the glottis open. Or the
MECHANICS OF THE CIRCULATION IN THE VESSELS 129
'mouth may be. connected with the recording apparatus, the nostrils
being closed. One factor in the production of these movements may
be the change of blood- volume in the soft tissues of the mouth, naso-
pharynx, and perhaps also in the lower respiratory passages accom-
panying the heart-beat. Another factor, and a more influential one,
is the rhythmical alteration of pressure caused directly by the alter-
nate systole and diastole of the heart in the air contained in the
lung-tissue surrounding it, which acts as a kind of air plethysmo-
graph. One interesting way in which the cardio-pneumatic move-
ments may reveal themselves is by a variation with each beat of the
heart in the intensity of a note prolonged in singing, especially after
fatigue has set in. Upon the whole, the air-pressure falls during
systole, owing to the expulsion of blood from the chest, and rises
during diastole. The main cardio-pneumatic movement is, there-
fore, a systolic inspiration and a diastolic expiration (Practical
Exercises, p. 303).
Doubtless the weight of an organ would also show a pulse correspond-
ing to the beat of the heart, and so would the temperature^-at least,
of the superficial parts. For the amount of heat given off by the blood
Fig- 57- — Plethysmograph Tracing from Arm. The tracing was taken by means 01
a tambour connected with the plethysmograph. The dicrotic wave is distinctly
marked.
to the skin increases with its mean velocity, and, therefore, although
the difference may not in general be measurable, more heat is pre-
sumably given off during the systolic increase of velocity than during
the diastolic slackening. And this, along with other considerations,
suggests that, at any rate in certain situations and under certain con-
ditions, there may even be a pulse of chemical change ; that is, a slight
and as yet doubtless inappreciable ebb and flow of metabolism corre-
sponding to the rhythm of the heart.
The Circulation in the Capillaries. — From the arteries the blood
passes into a network of narrow and thin- walled vessels, the capil-
laries, which in their turn are connected with the finest rootlets of
the veins. Physiologically, the arterioles and venules must for
many purposes be included in the capillary tract, but the great
anatomical difference — the presence of circularly-arranged muscular
fibres in the arterioles, their absence in the capillaries — has its
9
130
physiological correlative. The calibre of the arterioles can be
altered by contraction of these fibres under nervous influences; the
calibre of the capillaries, although it varies passively with the blood-
pressure, and is possibly to some extent affected by active con-
traction of the endothelial cells, cannot be under the control of vaso-
motor nerves acting on muscular fibres (but see p. 173).
Harvey had deduced from his observations the existence of
channels between the arteries and the veins. Malpighi was the first
to observe the capillary blood-stream with the microscope, and thus
to give ocular demonstration of the truth of Harvey's brilliant
reasoning. He used the lungs, mesentery and bladder of the frog.
The web of the frog, the tail of the tadpole, the wing of the bat, the
mesentery of the rabbit and rat, and other transparent parts, have
also been frequently employed for such investigations. From the
apparent velocity of the corpuscles and the degree of magnification,
Fig- 58- — Diagram to illustrate the Slope of Pressure along the Vascular System.
A, arterial; C, capillary; V, venous tract. The interrupted line represents the
line of mean pressure in the arteries, the wavy line indicating that the pressure
varies with each heart-beat. The line passes below the abscissa axis (line of
zero or atmospheric pressure) in the veins, indicating that at the end of the venous
system the pressure becomes negative.
it is easy to calculate the velocity of the capillary blood-stream.
It has been estimated at from 0-2 to 0-8 mm. per second in different
parts and different animals.
The comparative slowness of the current and the disappearance
of the pulse are the chief characteristics of the capillary circulation.
The explanation we have already found in the great resistance of
the narrow arterioles and the much-branched capillary vessels.
Although the average diameter of a capillary is only about 10 u,
(5 to 20 ft in different parts of the body), the number of branches
is so prodigious that the total cross-section of the systemic capillary
tract has been estimated at 500 to 700 times that of the aorta.
Such estimates are, of course, by no means exact.
The total cross-section of the vascular channel gradually widens
as it passes away from the left ventricle. In the capillary region
it undergoes a great and sudden increase. A part of this increase
is to be attributed to the arterioles, which, although individually
very narrow, have a total bed considerably greater than that of the
arteries from which they spring. Where the arterioles pass into
the capillaries proper, a further and a still greater and more abrupt
increase in the bed occurs. At the venous end of this region the
cross-section is again somewhat abruptly contracted, and then
gradually lessens as the right side of the heart is approached; but
the united sectional area of the large thoracic veins is greater than
that of the aorta.
Attempts have been made to measure the blood-pressure in the
capillaries by weighting a small plate of glass laid on the back of one of
the fingers behind the nail, until the capillaries are just emptied, as
shown by the paling of the skin (v. Kries), or by observing the height of
a column of liquid that
just stops the circula-
tion in a transparent
part (Roy and Graham
Brown). The last-
named observers found
that a pressure of 100
to 150 mm. of water
(about 7 to ii mm.
of Hg) was needed to
bring the blood to a
standstill in the capil-
laries and veins of the
frog's web; that is,
about a third of the
blood-pressure in the
frog's aorta. The pres-
sure in the capillaries
at the root of the nail
Fig. 59. — Relation of Blood- Pressure, Velocity, and
Cross-Section. The curves P, V, and S represent the
blood-pressure, velocity of the blood, and total cross-
section respectively in the arteries A, capillaries C,
and veins V.
in man varies from
30 to 50 mm. of mercury, as estimated by the method of v. Kries. But
the method is exposed to serious errors. The method of measuring the
venous pressure described on p. 132 can also be applied to the capillaries,
and is somewhat more satisfactory.
Under certain conditions the pulse-wave may pass into the
capillaries and appear beyond them as a venous pulse. Thus, we
shall see that when the small arteries of the submaxillary gland are
widened, and the vascular resistance lessened, by the stimulation of
the chorda tympani nerve, the pulse passes through to the veins.
And, normally, a pulse may be seen in the wide capillaries of the
nail-bed — especially when they are partially emptied by pressure —
as a flicker of pink that comes and goes with every beat of the heart.
We have seen that the lateral pressure at any point of a uniform
rigid tube through which water is flowing is proportional to the amount
of resistance in the portion of the tube between this point and the outlet.
In any system of tubes the sum of the potential and kinetic energy
must diminish in the direction of the flow; and although the problem
132 THE CIRCULATION OF THE BLOOD AND LYMPH
is complicated in the vascular system by the branching of the channel
and the variation in the total cross-section, yet theory and experiment
agree that in the larger arteries the lateral pressure diminishes but
slowly from the heart to the periphery, the resistance being small com-
pared with the resistance of the whole circuit. In the capillary region
the vascular resistance abruptly increases; the velocity (and therefore
the kinetic energy) abruptly diminishes, and the lateral pressure falls
much more steeply between the beginning and the end of this region
than between the heart and its commencement. In the veins only a
small remnant of resistance remains to be overcome, and the lateral
pressure must sink again rather suddenly about the end of the capillary
tract. Fig. 59 shows by a rough diagram the manner in which the
pressure, velocity and cross-section probably change from part to part
of the vascular system.
The Circulation in the Veins. — The slope of pressure, as we have
just explained, must fall rather suddenly near the beginning and
near the end of the capillary tract. It continues falling as we pass
along the veins, till the heart is again reached. In the right heart,
and in the thoracic portions of the great veins which enter it, the
pressure may be negative — that is, less than the atmospheric
pressure. And since nowhere in the venous system is the pressure
more than a small fraction of that in the arteries, its measurement
in the veins is correspondingly difficult, because any obstruction
to the normal flow is apt to artificially raise the pressure. A man-
ometer containing some lighter liquid than mercury, such as water
or a solution of sodium citrate or magnesium sulphate, is usually
employed, so that the difference of level may be as great as possible.
In the sheep the pressure was found to be 3 mm. of mercury in the
brachial, and about u mm. in the crural vein. Burton-Opitz
obtained the following pressures in dogs (of about 15 kilos): left
facial vein, 5-1 ; right external jugular, - o-ii ; central end of superior
vena cava, — 2'8; femoral vein, 5-4; renal vein, 10-9; portal vein,
8' 9 mm. of mercury.
Estimation of Venous Pressure in Man. — The venous pressure in man
has been estimated by several observers with more or less satisfactory
results. The best-known method is that of v. Recklinghausen. A
circular rubber bag, with a central opening, is laid over the course of
a vein, so that the vein can be observed through the opening, as in
Fig. 60. The bag is smeared with glycerin. A glass plate is laid over
the opening and held firmly, so that the vein and the surrounding skin
are in a closed chamber. The bag is provided with a side-tube, which
connects it with a pump and a water manometer. By means of the
pump air is forced into the bag till the vein is just seen to collapse.
The pressure indicated on the manometer at this moment is taken as
the pressure in the vein.
By means of a modification in this method, Eyster and Hooker have
found that the pressure in the small veins of the arm or hand generally
varies between 3 and 10 cm. of water. In conditions of congestion of
the venous system the pressure may rise to 20 cm. of water (say 15 mm.
of mercury) or more.
In making this measurement it is necessary to take account of the
MECHANICS OF THE CIRCULATION IN THE VESSELS 133
position of the vein, since the hydrostatic factor (p. igo) in the venous
pressure is so important. Thus it is obvious that the pressure in the
veins of the hand will be greater when it is hanging down than when
it is raised to level of the heart or above it. Accordingly, the actual
readings of the manometer must always be corrected for the vertical
distance between the vein and the heart, the' height of a column of
blood equal to this distance being deducted from or added to the
manometer reading, according to whether the vein is below or above
the heart level. For practical purposes the heart level is supposed to
correspond to the lower end of the sternum (costal angle).
For the measurement of the pressure in the right auricle, the follow-
ing simple and elegant method has been given by Gaertner, following
a suggestion of Frey: He raises the arm of the sitting patient, and
observes a small vein on the back of the hand. At the moment when the
vein collapses the elevation of the arm is stopped, and the vertical
distance between the vein and the heart measured. This expressed in
millimetres of blood (i.e., approximately of water) is the pressure in
the auricle, since the veins of the arm constitute manometer tubes
connected with the auricle.
The venous pressure being so low, or, in other words, the potential
energy which the systole of the heart imparts to the blood being so
greatly exhausted /t
before it reaches
the veins, other in-
fluences begin here
appreciably to
affect the blood-
stream :
1. Contraction of
the Muscles. — This
compresess the
neighbouring veins,
and since the blood is compelled by the valves, if it moves at
all, to move towards the heart, the venous circulation is in this
way helped.
2. Aspiration of the Thorax. — In inspiration the intrathoracic
pressure, and therefore the pressure in the great thoracic veins, is
diminished, and blood is drawn from the more peripheral parts of
the venous system into the right heart (p. 226).
3. Aspiration of the Heart. — When the heart after its contraction
suddenly relaxes, the endocardiac pressure becomes negative, and
blood is sucked into it, just as when the indiarubber ball of a syringe
is compressed and then allowed to expand. But we cannot attribute
any great importance to this; and, of course, it is only the relaxa-
tion of the right ventricle which could directly affect the venous
circulation.
4. Every change of position of the limbs, as in walking, aids the
venous circulation (Braune), and this independently of the muscular
contraction. When the thigh of a dead body is rotated outwards, and
Fig. 60. — Diagram of Measurement of Venous Pressure
(v. Recklinghausen). H, back of hand, with V, a vein;
B, the rubber bag with central opening; T, tube leading
from bag to manometer and pump ; G, glass plate.
134 THE CIRCULATION OF THE BLOOD AND LYMPH
at the same time extended, a manometer connected with the femoral
vein shows a negative pressure of 5 to 10 mm. of water. When the
opposite movements are made, the pressure becomes positive.
It follows from the number of casually-acting influences which
affect the blood-flow in the veins that it cannot be very regular or
constant. We have seen that in the great arteries there is a con-
siderable variation of velocity and of pressure with every discharge
of the ventricle, and although this variation is absent from the
veins, since normally the pulse, due to the ventricular discharge,
does not penetrate into them, the venous flow is, nevertheless, as a
matter of fact, more irregular than the arterial. So that if it is
difficult to give a useful definition of the term ' velocity of the
blood ' in the case of the arteries, it is still more difficult to do so in
the case of the veins. Where voluntary movement is prevented,
one potent cause of variation in the venous flow is eliminated; and
in curarized animals certain observers have found but little differ-
ence between the mean velocity in the veins and in the corre-
sponding arteries. Others have found the velocity in the veins
considerably less, which is indeed what we should expect from the
fact that the average cross-section of the venous system is greater
than that of the arterial system. Burton-Opitz, by means of a
stromuhr, obtained a mean velocity of 147 mm. per second in the
external jugular vein of a 13-kilo dog.
To sum up, we may conclude that, upon the whole, the blood
passes with gradually-diminishing velocity from the left ventricle
along the arteries; it is greatly and somewhat suddenly slowed in the
broad and branching capillary bed; but the stream gathers force
again as it becomes more and more narrowed in the venous channel,
although it never acquires the speed which it has in the aorta.
Venous Pulse. — To complete the account of the circulation in the
veins, it may be recalled that, in addition to the venous pulse
described on p. 131, which, as an occasional phenomenon, may
travel through widened arterioles and capillaries from the arteries
into the veins, and therefore in the direction of the blood-stream,
a so-called venous pulse, travelling from the heart against the blood-
stream and depending on variations of pressure in the right auricle,
may be detected in the jugular veins in healthy persons, and more
distinctly in certain disorders of the circulation, where indeed it
may be evident at a greater distance from the heart — for example,
over the liver as the so-called liver pulse. In animals a venous
pulse of this nature has been demonstrated in the venae cavae, the
jugular vein, and with a delicate manometer even in the large veins
of the limbs. It moves with a speed of I to 3 metres a second
(Morrow). It is most easily observed in the jugular veins in man,
because of their proximity to the heart. We have already pointed
out the significance of the study of this venous pulse for the analysis
MECHANICS OF THE CIRCULATION IN THE VESSELS 135
of cardiac events (p. 100). A jugular venous pulse of a perfectly
different origin is seen in cases of incompetence of the tricuspid
valve. Here the chief elevation is synchronous with the ventricular
systole, and is caused by the regurgitation of blood from the right
ventricle through the auricle into the veins. The so-called ' com-
municated venous pulse ' is simply due to the proximity of some
large artery, especially when enclosed in a common sheath, whose
pulsations are directly transmitted to the vein. The changes of
pressure in the great veins accompanying the respiratory move-
ments (p. 290) are also sometimes spoken of as a venous pulse, but
they are produced in a different way — namely, by the rhythmical
alteration in the intrathoracic pressure, which alternately favours
and hinders the venous return to the heart.
The Circulation-Time. — Hering was the first who attempted to
measure the time required by the blood, or by a blood-corpuscle, to
complete the circuit of the vascular system. He injected a solution of
potassium ferrocyanide into a vein (generally the jugular), and collected
blood at intervals from the corresponding vein of the opposite side.
After the blood had clotted, he tested for the ferrocyanide by addition
of ferric chloride to the serum. The first of the samples that gave the
Prussian blue reaction corresponded to the time when the injected salt
had just completed the circulation. This method was improved by
Vierordt, who arranged a number of cups on a revolving disc below the
vein from which the blood was to be taken. In these cups samples of
the blood were received, and the rate of rotation of the disc being known,
it was possible to measure the interval between the injection and appear-
ance of the salt with considerable accuracy. Hermann made a further
advance by allowing the blood to play upon a revolving drum covered
with paper soaked in ferric chloride, and by using the less poisonous
sodium ferrocyanide for injection.
Even as thus modified, the method laboured under serious defects.
It was not possible to make more than a single observation on one
animal, at least without allowing a considerable interval for the elimina-
tion of the ferrocyanide, and, further, the method was unsuited for the
estimation of the circulation-time in individual organs. In both of
these respects the more recently introduced electrical method presents
considerable advantages; for by its aid we can not only obtain satis-
factory measurements of the circulation-time in such organs as the
lungs, liver, kidney, etc., but we can repeat them an indefinite number
of times on the same animal.
A cannula, connected with a burette (or a Mariotte's bottle, or a
syringe), containing a solution of sodium chloride (usually a 1*5 to
2 per cent, solution), is tied into a vessel — say the jugular vein. Sup-
pose that the time of the circulation from the jugular to the carotid is
required — that is, practically the time of the lesser or pulmonary circu-
lation. A small portion of one carotid artery is isolated, and laid on
a pair of hook-shaped platinum electrodes,* covered, except on the
concave side of the hook, with a layer of insulating varnish. To
further secure insulation, a bit of very thin sheet -indiarubber is slipped
between the artery and the tissues. By means of the electrodes the
* The electrodes can easily be made by beating out one end of a piece of
thick platinum wire to a breadth of 5 or 6 mm., and then bending the flattened
part into a hook, or by bending pieces of stout platinum foil,
136
THE CIRCULATION OF THE BLOOD AND LYMPH
piece of artery lying between them, with the blood that flows in it, is
connected up as one of the resistances in a Wheatstone's bridge (p. 726).
The secondary coil of a small inductorium, arranged for giving an inter-
rupted current, and with a single Daniell or dry cell in its primary, is
substituted for the battery, and a telephone for the galvanometer,
according to Kohlrausch's well-known method for the measurement of
the resistance of electrolytes. It is well to have the induction machine
set up in a separate room and connected to the resistance-box by long
wires, so that the noise of the Neefs hammer may be inaudible. The
bridge is balanced by adjusting the resistances until the sound heard
in the telephone is at its minimum intensity, the secondary coil being
placed at such a distance from the primary that there is no sign of
stimulation of muscles or nerves in the neighbourhood of the electrodes
Fig. 61. — Measurement of the Pulmonary Circulation -Time in Rabbit by Injection
of Methylene Blue.
when the current is closed. A definite, small quantity of the salt solu-
tion is now allowed to run into the vein by turning the stop-cock of the
burette. It moves on with the velocity of the blood, and reaching the
artery on the electrodes causes a diminution of its electrical resistance
(p. 26). This disturbs the balance of the bridge, and the sound in the
telephone becomes louder. The time from the beginning of the injec-
tion to the alteration in the sound is the circulation - time between
jugular and carotid. It can be read off by a stop-watch, or more
accurately by an electric time-maker writing on a revolving drum
(Fig. 62). Instead of the telephone a galvanometer may be used, the
equal and oppositely directed induction shocks being replaced by a
weak voltaic current, and the platinum by unpolarizable electrodes
(p. 731). But this is less convenient.
137
The circulation-time of an organ like the kidney can be measured by
adjusting a pair of electrodes under the renal artery and another under
the renal vein, and reading off the interval required by the salt solution
to pass from the point of injection first to the artery and then to the
vein. The difference is the circulation -time through the kidney.
For certain purposes, and particularly for measurements on small
animals like the rabbit, or on organs whose vessels are too delicate to
be placed on electrodes without the risk of serious interference with
the circulation, another method may be employed with advantage. It
depends on the injection of a pigment, like methylene blue, which at
first overpowers the colour of the blood and shows through the walls of
the bloodvessels, but is soon reduced to a colourless substance (Fig. 61).
The details of the method are given in the Practical Exercises (p. 217.)
It may be said in general terms that in one and the same animal
the time of the lesser circulation is short as compared with the total
circulation-time, relatively constant, and but little affected by changes
of temperature. In animals of the same species it increases with the
size, but more slowly, and rather in proportion to the increase of
surface than to the increase of weight.
Thus a dog weighing 2 kilogrammes had an average pulmonary
circulation-time of 4*05 seconds, while that of a dog weighing ir8 kilos
was 8*7 seconds, and that of a dog with a body-weight of 18*2 kilos only
ip'4 seconds. It is probable that in a man the pulmonary circulation-
time is not usually much less than 12 seconds, nor much more than
15 seconds.
The circulation-time in the kidney, spleen and liver is relatively
long and much more variable than that of the lungs, being easily
affected by exposure and changes of temperature (increased by
cold, diminished by warmth).
In a dog of 13-3 kilos weight the average circulation-time of the
spleen was 10-95 seconds; kidney, 13-3 seconds; lungs, 8-4 seconds.
The circulation-time of the stomach and intestines is (in the rabbit)
comparatively short, not exceeding very greatly that of the lungs,
but it is lengthened by exposure. The circulation-time of the
retina and that of the heart (coronary circulation) are the shortest
of all.
The total circulation-time is properly the time required for the whole
of the blood to complete the round of the pulmonary and systemic
circulation. But there are many routes open to any given particle of
blood in making its systemic circuit. If it passes from the aorta through
the coronary circulation it takes an exceedingly short route. If it passes
through the intestines and liver, or through the kidney, or through the
lower limbs, it takes a long route. So that to determine the total cir-
culation-time by direct measurement we must know (i) the quantity
of blood that passes on the average by each path in a given time, and
(2) the average circulation-time of each path. If the average weight of
blood in each organ be represented by w^, wz, w3, etc. ; and the average
circulation-times by tlt tz, t3, etc. ; and t be the total systemic circulation.
time ; then WJ-T , w^. , w^. , etc., will represent the quantity of blood
passing through each organ in t seconds, since in the average circula-
THE CIRCULATION OF THE BLOOD AND LYMPH
tion-time of an organ the whole of the blood in it at the beginning of
the period of observation will have been exchanged for fresh blood.
But the whole of the blood in the body, which we may call W, passes
once round the systemic circulation in t seconds. Therefore,
w^-r + a>^7 +to3— , etc., =W. In this equation everything can be de.
*1 '2 *3
termined by experiment except t, and therefore t can be calculated.
Adding t to the pulmonary circulation -time, we arrive at the tota
circulation -tune .
Although our experimental data are as yet too meagre to make the
calculation more than a rough approximation, it appears probable that
in certain animals the total circulation-time is five or six times as great
as the pulmonary circulation -time. If the same ratio holds good in
man, the total circulation-time is unlikely to be much less than a minute
. or much greater than a
_ | 1 . minute and a quarter.
We shall see directly
that this estimate is
confirmed by data de-
rived from a different
source. In the mean-
time, we may use it
II
m
provisionally to calcu-
late the work done by
the heart. Let us take
for simplicity the total
circulation - time as i
minute in a 70 -kilo
man, the quantity of
blood as 4 £ kilos, * and
the mean pressure in
the aorta as 150 nun.
of mercury. Up to the
time when the semi-
lunar valves are opened ,
the work done by the
left ventricle is spent
in raising the intra ven-
tricular pressure till it
is sufficient to over-
come the pressure in
the aorta. If a vertical
tube were connected
with the left ventricle,
the blood would rise till
the column was of the same weight as a column of mercury of equal section
and 150 mm. high. This column of blood would be about 1-92 metres in
height. If a reservoir were placed in communication with the tube at
this height, a quantity of blood equal to that ejected from the ventricle
would at each systole pass into the reservoir; and the work which the
blood thus collected would be capable of doing, if it were allowed to
fall to the level of the heart, v/ould be equal to the work expended by
the heart in forcing it up. Thus, in i minute the work of the left ven-
tricle would be equal to that done in raising 4^ kilos of blood to a height
* The mean of the 5^ kilos given by most writers, and of the 3^ kilos ob-
tained by Haldane and Smith (p. 56).
_JLJL.fl .0-JLJLJLJlJLJl-n-JLJLJ B HJLJLJl
Fig. 62. — Time of the Lesser Circulation. Cat anaes-
thetized with Ether. Time-trace, seconds. The line
above the time-trace was written by an electro-
magnetic signal, the circuit of which was closed at
the moment when injection of methylene blue into
the jugular vein was begun, and opened at the
moment when the change of colour in the carotid
was observed. I, normal circulation-time; II, cir-
culation-time after section of both vagi (much
diminished) ; III, circulation-time during stimulation
of the peripheral end of one vagus (much increased).
MECHANICS OF THE CIRCULATION IN THE VESSELS 139
of i'92 metres — that is, about 8^64 kilogramme-metres; in 24 hours it
would be, say, 12,450 kilogramme-metres. Taking the mean pressure
in the pulmonary artery at one-third of the aortic pressure, we get for
the daily work of the right ventricle about 4,150 kilogramme -metres.
The work of the two ventricles is thus about 16,600 kilogramme-metres,*
which is enough to raise a weight of nearly 4 pounds from the bottom
of the deepest mine in the world to the top of its highest mountain, or
to raise the man himself to ij times the height of the spire of Strasburg
Cathedral, or twice the height of the loftiest ' skyscraper ' in New York.
By friction in the bloodvessels this work is almost all changed into its
equivalent of heat, nearly 40,000 gramme-calories (p. 688) . Further, since
the contraction of the heart is always maximal (p. 154), and there is
reason to believe that the quantity of blood ejected at a single systole
by the left ventricle (being dependent upon the inflow from the pulmon-
ary veins, and therefore upon the inflow into the right side of the heart
from the systemic veins) varies widely, some of the mechanical effect
of the contraction must be wasted when the quantity is less than the
ventricle is capable of expelling.
Output of the Heart. — If 4$ kilos of blood pass through the heart in
i minute with the average pulse-rate of 72 per minute, the quantity
ejected by either ventricle with every systole will be — — =62-5 grm.,
or a little less than 60 c.c. The output may be expressed in grammes
or cubic centimetres per minute (the minute volume), or per second, or
per beat. It has been measured in animals in several ways — e.g., by
inserting a stromuhr (p. 121) on the course of the aorta, or by recording
the variations in the volume of the heart, or, better, of the ventricles,
by means of a plethysmograph (cardiometer of Henderson), in which
the organ is enclosed. Another method, which does not entail the
opening of the chest, is to allow a salt solution to run slowly, for a de-
finite number of seconds, into the left ventricle through a tube passed
into it from the carotid artery. A sample of the mixture of blood and
salt solution is collected from a branch of the femoral artery, where its
arrival is detected by the change of electrical resistance (p. 135). From
the amount of salt solution which must be added to a normal sample
of blood drawn before the injection to make its conductivity the same
as that of the sample taken during the passage of the mixture, the
quantity of blood with which the solution was mixed in the ventricle
during the injection can be approximately determined. By this method
it has been shown in a series of experiments on more than twenty dogs,
ranging in weight from 5 to nearly 35 kilos, that the output of the
left ventricle per kilo of body-weight per second diminishes as the size
of the animal increases ; and the relation between body-weight and out-
put is such that in a man weighing 70 kilos we can hardly suppose that
the ventricle discharges, during bodily rest, more than 105 grm. of
blood per second, or 87 grm. (80 c.c.) per heart-beat with a pulse-rate
of 72. Putting this result along with that deduced from the circulation-
time, we can pretty safely conclude that the average amount of blood
thrown out by each ventricle at each beat is not more than 70 or 80 c.c.
Zuntz, from the quantity of oxygen absorbed by the blood in the lungs
in a definite short time, and the difference between the oxygen content
of samples of the arterial and venous blood, has estimated the output
per beat at 60 c.c. But according to him this may be doubled during
* Since the blood on expulsion is moving with a certain velocity, an addi-
tion might be made for its kinetic energy. But this would only increase the
total work by a small fraction (about i per cent.).
140 THE CIRCULATION OF THE BLOOD AND LYMPH
severe muscular work, when, as a matter of fact, by the aid of the
Rontgen-rays or by percussion of the chest, the volume of the heart
may be shown to be considerably increased. Tigerstedt, on the basis
of stromuhr measurements in animals, puts the ventricular output per
beat in man at 50 to 100 c.c. ; Plesch, on the basis of gasometric ob-
servations on man, at 59 c.c. Recently Krogh, using a gasometric
method based on the absorption of nitrous oxide gas in the lungs, found
that the minute volume during rest may vary between wide limits
(2-8 to 8'7 litres of blood per minute, corresponding, with a pulse-rate
of 70, to 40 c.c. to 120 c.c. per beat). During muscular work there is
a great and immediate Increase, up to, it may be, 21-6 litres per minute.
These great variations in the output of the ventricle depend primarily
upon variations in the rate of return of the blood to the heart by the
veins. According to Henderson, however, such great variations in the
output per beat as are postulated by the majority of physiologists who
have worked at the subject do not occur, and the fundamental variable
is the rate of the beat.
In healthy persons in whom the pulse-rate is permanently much
below the normal (p. 107) the output of the ventricle per beat must, of
course, be correspondingly increased. In a man with a pulse -rate
always below 40 during rest in the sitting position, the flow in the hands
was found to be normal in amount, and all the signs of a normal delivery
of blood from the left ventricle were present. Here the output per
beat must have been twice the usual amount during rest.
SECTION IV. — THE HEART-BEAT IN ITS PHYSIOLOGICAL
RELATIONS.
So far we have been considering the circulation as a purely
physical problem. We have spoken of the action of the heart as
that of a force-pump, and perhaps to a small extent that of a suction-
pump too. We have spoken of the bloodvessels as a system of more
or less elastic tubes through which the blood is propelled. We have
spoken of the resistance which the blood experiences and the pressure
which it exerts in this system of tubes, and we have considered the
causes of this resistance, the interpretation of this pressure, and the
physical changes in the vascular system that may lead to variations
of both. But so far we have not at all, or only incidentally and very
briefly, dealt with the physiological mechanism through which the
physical changes are brought about. We have now to see that,
although the heart is a pump, it is a living pump ; that, although the
vascular system is an arrangement of tubes, these tubes are alive;
and that both heart and vessels are kept constantly in the most
delicate poise and balance by impulses passing from the central
nervous system along the nerves.
In many respects, and notably as regards the influence of nerves
on it, we may look upon the heart as an expanded, thickened and
rhythmically-contractile bloodvessel, so that an account of its
innervation may fitly precede the description of vaso-motor action
in general.
THE HEART-BEAT IN ITS PHYSIOLOGICAL RELATIONS 141
The Relation of the Heart to the Nervous System. — A very simple
experiment is sufficient to prove that the beat of the heart does not
depend on its connection with the central nervous system, for an
excised frog's heart may, under favourable conditions, of which the
most important are a moderately low temperature, the presence of
oxygen, and the prevention of evaporation, continue to beat for days.
The mammalian heart also, after removal from the body, beats for
a time, and indeed, if defibrinated blood be artificially circulated
through the coronary vessels, for several or even many hours. But
although this proves that the heart can beat when separated from
the central nervous system, it does not prove that nervous influence
is not essential to its action, for in the cardiac substance nervous
elements, both cells and fibres, are to be found.
The Intrinsic Nerves of the Heart. — In the heart of the frog
numerous nerve-cells occur in the sinus venosus, especially near its
junction with the right auricle (Remak's ganglion). A branch
from each vagus, or rather from each vago-sympathetic nerve (for
in the frog the vagus is joined a little below its exit from the skull
by the sympathetic), enters the heart along the superior vena cava
(pp. 157, 198).
Running through the sinus, with whose ganglion-cells the true vagus
fibres, or some of them, are believed to make physiological junction
(p. 163), the nerves pursue their course to the auricular septum. Here
they form an intricate plexus, studded with ganglion-cells. From the
plexus nerve-fibres issue in two main bundles, which pass down the
anterior and posterior borders of the septum to end in two clumps of
nerve-cells (Bidder's ganglia), situated at the auriculo-ventricular
groove. These ganglia in turn give off fine nerve-bundles to the ven-
tricle, which form three plexuses — one under the pericardium, another
under the endocardium, and a third in the muscular wall itself, or myo-
cardium. From the last of these plexuses numerous non-medullated
fibres run in among the muscular fibres and end in close relation with
them. Similar plexuses of nerve-fibres exist in the mammalian ventricle.
But while scattered ganglion-cells are found in the upper part of the
ventricular wall, most observers have been unable to demonstrate any
either in the mammal or the frog in the apical half. In the rat's heart,
according to the careful observations of Schwartz, true ganglion-cells
are confined to an area on the posterior surface of the auricles, lying
always under the visceral pericardium. Other writers, however, have
stated that ganglion-cells do exist in the apex both of the cat's and of
the frog's heart. In connection with the whole question it must be
borne in mind that in other organs improved histological methods have
brought typical nerve-cells to light in situations where they were not
suspected or were denied to exist, and. further, that all investigators
are not agreed upon the histological criteria by which ganglion-cells are
to be distinguished.
Cause of the Rhythmical Beat of the Heart. — Scarcely any physio-
logical question has excited greater interest for many "years than the
mechanism of the heart-beat. Several properties of the cardiac
tissue ought to be distinguished in discussing this question: (i) Its
I42 THE CIRCULATION OF THE BLOOD AND LYMPH
automatism — i.e., its power of beating in the absence of external
stimuli; (2) its rhythmicity — i.e., its power of responding to con-
tinuous stimulation by a series of rhythmically repeated contrac-
tions; (3) its conductivity — i.e., its power of conducting the contrac-
tion wave or the impulse to contraction once it has been set up ; and
(4) the power of co-ordination, in virtue of which the various parts
of the heart beat in a regular sequence.
The excitability of the cardiac tissue — that is, its power of appro-
priate response (namely, by contraction) to a suitable stimulus —
does not particularly concern us here, since it is in no wise a property
special to the heart. Only, as we shall see in the sequel, the time-
relations of this excitability are of interest, for the existence of a
refractory period — that is, an interval during which the cardiac
muscle refuses to respond to excitation — throws light upon the
rhythmicity of the heart-beat. The tonicity of the heart — i.e., its
power of remaining contracted to a certain extent in the intervals
between successive beats — is another property of great importance
in certain aspects, but which only needs to be mentioned at present.
Automatism of the Heart-Beat — Neurogenic and Myogenic Hypo-
theses.— That the heart-beat is automatic is sufficiently shown by
the fact that, as already mentioned, an excised and empty heart
will go on beating for a time, for many hours or even for days in the
case of cold-blooded animals. When blood, or even a suitable
solution of such inorganic salts as exist in serum, is caused to circu-
late through the coronary vessels of the excised heart of a warm-
blooded animal, it also continues to contract for a long time. In
trying to understand the real significance of the automatic beat of
the heart, physiologists have endeavoured, first, to compare different
portions of the heart as regards the degree in which they possess this
property of automaticity ; and, second, to associate, if possible, one
or other of the active tissues that compose the organ, muscle, and
nervous tissue, with this characteristic property. It cannot be
pretended that a final answer to this question is possible at present.
Nor is the historical controversy which it has occasioned perhaps as
important in itself as the space usually devoted to it in textbooks
might imply. Yet it is probable that the series of fundamental
facts in the physiology of the heart elicited in the long discussion can
be best presented, even for the purposes of the elementary student,
as they were originally brought forward in the form of pros and
cons, of arguments for and against the neurogenic or the myogenic
hypothesis. There is good evidence that as in the amphibian
heart the contraction starts in the sinus venosus, so in the mam-
malian heart it starts in the sinus tissue of the right auricle in the
region of the sino-auricular node. Attempts have been made to
demonstrate that the origination of the impulses which are after-
wards conducted to all parts of the heart is normally confined to
THE HEART-BEAT IN ITS PHYSIOLOGICAL RELATIONS 143
the node itself, and the sino-auricular node is by some authors
denominated the pace-maker of the heart, the tissue which sets the
pace for the rest of the organ and gives the time to auricles and
ventricles alike. The experimental results, however, are by no
means harmonious, some observers finding that destruction of the
region of the node causes no change in the rate of the heart-beat,
others that the beat is permanently slowed. But even were we in
a position to sharply delimit a given region of the heart as the point
at which the strong tendency to contraction inherent in the cardiac
tissue as a whole first breaks into an actual beat, this would scarcely
enable us to decide offhand where the cause of the automatism
resides, in the muscular tissue or in the intrinsic nervous apparatus,
because in nearly all animals hitherto investigated the muscular
tissue, ganglion-cells, and nerve-fibres are inseparably intermingled.
In Limulus, however, the horseshoe or king crab, the cardiac
ganglion-cells are collected in a nerve-cord running longitudinally in
the median line along the dorsal surface of the segmented heart, and
Fig. 63. — The Heart ana che Heart Nerves of Limulus: Dorsal View (Carlson). (The
heart is figured one-half the natural size of a large specimen.) aa, Anterior
artery; la, lateral arteries; In, lateral nerves; mnc, median nerve-cord; os, ostia.
sending off at intervals branches to two lateral cords, and also
branches which enter the heart muscle directly (Fig. 63). When
the median nerve-cord is§me way a
portion of the heart, such as the apex of the ventricle, when stimu-
lated in the quiescent condition by an interrupted current, responds
by a rhythmical series of beats, and not by a tetanus. It is evident
that the cardiac muscle, like ordinary striped muscle, is for some
time after excitation incapable of responding to a fresh stimulus —
i.e., there is a relractory period^ But this is immensely longer in
cardiac than in skeletal muscle. When the phenomenon is analyzed,
it is found that a stimulus falling into the heart muscle between the
moment at which the contraction begins and the moment at which
it reaches its maximum produces no effect — is, so to speak, ignored.
When the stimulus is thrown in at any point between the maximum
of the systole and the beginning of the next contraction, it causes
what is called an extra contraction. The extra contraction is
followed by a longer pause than usual — a so-called compensatory
pause — which just restores the rhythm, so that the succeeding
systole falls in the curve where it would have fallen had there been
no extra contraction (Fig. 68).
In man, extra systoles followed by compensatory pauses may occur
under pathological conditions, giving rise to an important group of
cardiac irregularities. These extra systoles may be either auricular or
ventricular, the auricle or the ventricle contracting prematurely without
waiting for the signal of the sinus rhythm. The analysis of pulse-
tracings showing these irregularities has led to results of great physio-
logical and clinical interest (Cushny, Mackenzie, etc.), but cannot be
dwelt on here. When every second beat is an extra systole, generally
weaker than the preceding and the succeeding normal beat, the condi-
tion is called pulsus bigeminus. The weaker beat is always followed
by a compensatory pause of greater duration than that preceding it.
From the pulsus bigeminus must be distinguished that form of alterna-
ting pulse termed pulsus alternans, in which every second beat is dimin-
shed in size, but the intervals separating the beats are of uniform length.
THE CIRCULATION OF THE BLOOD AND LYMPH
The refractory period is shorter for strong than for weak stimuli,
and is markedly diminished by raising the temperature of the heart.
So that stimulation of the heated heart with a series of strong
induction shocks may cause a tetaniform condition, if not a typical
tetanus. The con-
traction of the
normally beating
heart is really a
simple contrac-
tion, and not a
tetanus. The
electrical changes
correspond to a
single contraction
(p. 833); and when
the nerve of a
nerve-muscle pre-
paration is laid
on the heart, the
muscle responds
to each beat by a
simple twitch,
and not by tet-
3. — Refractory Period and Compensatory Pause
A frog's heart was stimulated at a point corre-
sponding to the nick in the horizontal line below each
curve. In i and 2 there was no response ; in 3 and 4 there
was an extra contraction, succeeded by a compensatory
pause.
anus (p. 203).
That the cardiac
muscle itself, apart from the intrinsic nervous mechanism, shows
the phenomenon of ' refractory state ' has been shown in the
Limulus heart after extirpation of the ganglion (Carlson).
Like ordinary skeletal muscle, the cardiac muscle is at first bene-
fited by contraction, perhaps by an ' augmenting ' action of fatigue-
products such as carbon dioxide (Lee), so that when the apex is
stimulated at regular intervals each contraction is somewhat
stronger than the preceding one. To this phenomenon the name of
the staircase or ' treppe ' has been given, from the appearance of the
tracings (p. 749).
SECTION V. — THE NERVOUS REGULATION OF THE HEART
(EXTRINSIC NERVOUS MECHANISM OF THE HEART).
While, as we have seen, the essential cause of the rhythmical beat
of the heart resides in the tissue of the heart itself, it is constantly
affected by impulses that reach it from the central nervous system.
These impulses are of two kinds, or, rather, produce two distinct
effects: inhibition, shown by a diminution in the rate or force of the
heart-beat, or in the ease with which the contraction is conducted
over the heart-wall; and augmentation, or increase in the rate or
THE NERVOUS REGULATION OF THE HEART
'57
force of the beat or in the conductivity. Both the inhibitory and
th.3 augmentor impulses arise in the medulla oblongata, and perhaps
a narrow zone of the neighbouring portion of the cord ; and they can
be artificially excited by stimulation in this region. They pursue
their course to the heart by fibres which may in certain animals be
• mingled together, but are anatomically distinct. We may, there-
fore, divide the extrinsic or external nervous mechanisrr of the
heart into a cardio-inhibitory centre with its efferent inhibitory
nerve-fibres and a cardio-augmentor centre with its efferent acceler-
ator or augmentor fibres. Both of those centres, as we shall see,
have, in addition, extensive relations
with afferent nerve-fibres from all parts
of the body, including the heart itself.
It was in the vagus of the frog that
inhibitory nerves were first discovered
by the brothers Weber seventy years
ago, and even now our knowledge of the
cardiac nervous mechanism is more com-
plete in this animal than in any other.
We shall, therefore, first describe the
phenomena of inhibition and augmen-
tation as we see them in the heart of the
frog, and then pass on to the mammal.
In the frog the inhibitory fibres leave
the medulla oblongata in the vagus nerve.
The augmentor fibres come off from the
upper part of the spinal cord by a branch
from the third nerve to the third sympa-
thetic ganglion, and thence find their way
along the sympathetic cord to its junction
with the vagus, in which they run, mingled
with the inhibitory fibres, down to the heart.
When the vago-sympathetic in the
frog or toad is cut, and its peripheral
end stimulated, . the heart in the vast
majority of cases is stopped or slowed,
or its beat is distinctly weakened without, it may be, any marked
slowing. In other words, the rate at which the heart was
working before the stimulation is greatly diminished, or reduced
to- zero. Such an effect, a diminution of the rate of working,
we call Inhibition. What precise form the inhibition shall take,
whether the stoppage shall be complete or partial, and if partial
whether the beats shall be simply weakened without being slowed
or both slowed and weakened, appears to depend partly upon the
strength of the stimulus used and partly upon the state of the
heart itself. Some hearts it may be impossible to stop with weak
stimulation, although other signs of inhibition may be distinct;
Fig. 69. — Diagram of Extrinsic
Nerves of Frog's Heart (after
Foster). Ill, 3rd spinal
nerve; AV, annulus of Vieus-
sens; X, roots of vagus; IX.
glosso-pharyngeal nerve; VS.
combined vagus and sympa-
thetic; i. 2, and 3, the ist,
2nd, and 3rd sympathetic
ganglia. The dark line indi-
cates the course of the sym-
pathetic fibres. The arrows
show the direction of the aug-
mentor impulses.
158 THE CIRCULATION OF THE BLOOD AND LYMPH
while they are readily stopped by stronger stimulation. In other
cases the strongest stimulation may not produce complete standstill.
Again, the inhibitory effect produced on a heated heart by a given
strength of stimulation of the vagus may be greater than that caused
in a heart at the ordinary temperature or a cooled heart. This is
especially evident on the auricular tracings when these are recorded
separately from those of the ventricle. Even on the verge of heat
standstill of the heart inhibition is easily obtained (Fig. 71). Some
writers have assumed that the different inhibitory effects produced
by the vagus are due to the existence in it of separate groups of fibres,
some affecting only the rate of the contraction, others its strength,
Fig. 70. — Tracing from Frog's Heart. A, auricular, V, ventricular tracing. Sinus
stimulated (primary coil 70 mm. from secondary). Heart at temperature
11-2° C. Complete standstill. The time-tracing between the curves marks
intervals of two seconds.
others still the conductivity of the muscular tissue and its excita-
bility. This theory has enriched the vocabulary of physiology
with a number of sonorous terms derived from the Greek, but has
not otherwise established itself, although it has been ugfftil in
'emphasizing the fact that the inhibitory nerves can inflnenrp ^jie
heail "beat hi several distinct wavs.
~ but there are other points of importance to be noted in regard to
this inhibition : (i) It does not begin for a little time after stimulation
has begun. In other words, there is a distinct latent period; and
the length of this latent period is related to the phase of the heart's
THE NERVOUS REGULATION OF THE HEART
159
contraction at which the stimulus is thrown in, and to the rate at
which the heart is beating. As a general rule, the heart makes at
least one beat before it stops.^-" " . -
"(2)" The inhibition does not continue indefinitely, even if stimula-
tion of the nerve is kept up. Sooner or later, and usually, in fact,
afterari interval of a few seconds, the heart begins again to beat iTTt .^, ccO?*
haTbeencpmrjletelvstoppeo^ or to quicKen its beat if it has only b"een
slowed, or JxTstrengthen it n the inhibition has onlyj^e^ker^edjthe
j±s,oid rate oi
^
_
so, but very often there follows a longer or shorter period during
which the heart works at a greater rate than it did before the inhibi-
tion, and this greater rate of working may be manifested by increased
Fig. 71. — Activity of Vagus on Verge of Heat Standstill. Auricular and ventricular
contractions of toad's heart recorded. Heart at 34'5° C., v 50, stimulation of
vagus (distance of coils 50 mm.). The ventricle was already in heat standstill;
the auricle was at once inhibited. Then follows secondary augmentation (due
to the sympathetic fibres), during which the ventricle also resumes beating.
An interval of a minute elapsed between the first and second parts of the
tracing, during which the heart remained at 34'5° C. The auricle, was almost
in standstill (contractions can still be seen on the curve with a lens), when the
vagus was again stimulated at v 50 with the same distance between the coils.
Complete inhibition followed by secondary augmentation.
frequency of beat, or increased strength of beat, or by both. When
the temperature of the heart is low, increased frequency; when it is
high, increased strength, is generally seen during this period of
secondary augmentation. * The cause of this secondary augmentation,
and of the primary augmentation sometimes seen in fresh prepara-
tions and often in hearts that have been long exposed (Fig. 73),
excited much speculation before it was known that sympathetic
fibres existed in the vagus. There is no longer any doubt that it is
due to the stimulation of these accelerator or, as it is better to call
* Augmentation is termed ' secondary ' when it is preceded by inhibition,
primary ' when it is not so preceded
160 THE CIRCULATION OF THE BLOOD AND LYMPH
them (since mere acceleration is not the only consequence of their
stimulation), augmentor fibres in the mixed nerve. Fr»r lr\ pYrjfci-
tion of the roots of the vagus proper within the skull, and therefore
above the junction of the sympathetic fibres, causes no secondary
augmentation, or very little, and the inhibition lasts far longer than
when the mixed trunk is stimulated. (2) Excitation of the upper
or cephalic end of the sympathetic cord before it has joined the
vagus causes, after a relatively long latent period, marked augmenta-
tion. And if the contractions of the heart are registered, the
tracing bears a close resemblance to the curve of secondary augmen-
tation following excitation of the mixed nerve on the other side
with an equally strong stimulus and for an equal time. (3) When
the vago-sympathetic is stimulated weakly there is little or no
Fig. 72. — Frog's Heart: Vagus stimulated. Temperature of heart 8° C.; 78 mm.
between the coils. Diminution in force of auricle and ventricle, but not com •
plete standstill. Time-tracing shows two-second intervals.
secondary augmentation. Now, it is known that the augmentor
fibres require a comparatively strong stimulus to cause any effect
when they are separately excited, whereas a weak stimulus will
excite the inhibitory fibres.
The question arises at this point, why it is that, when the inhibitory
and augmentor fibres are stimulated together in the mixed nerve (and
the same is true when the sympathetic on one side and the vagus on
the other are stimulated at the same time), the inhibitory effect always
comes first, when there is any inhibitory effect, while the augmentation
always has to follow. The answer has sometimes been given, that the
latent period of the augmentor fibres is longer than that of the inhibitory
fibres. But although this is certainly the case, the answer is insuffi-
cient. For the period of postponement may be much greater than the
THE NERVOUS REGULATION OF THE HEART
161
latent period of the sympathetic fibres when stimulated by themselves.
The inhibition apparently runs its course without being affected by the
simultaneous augmcntor effect, which, lying latent until the end of the
inhibition, then bursts out and completes its own curve. It is not like
the passing of two waves through each other, but rather like the stopping
of one wave until the other has passed by. It seems as if augmentation
cannot develop itself in the presence of inhibition — at least, until the
latter is nearly spent. Like a musical-box devised to play a series of
melodies in a fixed order, and from which a particular tune cannot be
obtained till those preceding it have been run through, the heart, in
some way or other, is arranged, in the presence of competing impulses
from its extrinsic nerves, to play the tune of inhibition before the tune
Fig. 733. — Frog's Heart. A, auricular, V, ventricular tracing. Ventricle beating very
feebly. Vagus stimulated (60 mm. between coils). Marked augmentation of
ventricular beat.
of augmentation. In the frog, at any rate, the two processes can hardly
be considered as antagonistic, in the sense that a definite amount of
augmentor excitation can overcome a definite amount of inhibitory
excitation. Nor is it the case that, when the heart is played upon at
the same time by impulses of both kinds, it pits them against each other
and strikes the balance accurately between them. It is possible, how-
ever, that when the inhibitory fibres are very weakly, and the augmentor
fibres very strongly stimulated, the amount of inhibition may be some-
what diminished. In mammals, on the other hand, a true antagonism
seems to exist; and stimulation of the inhibitory nerves is less effective
when the augmentors are excited at the same time. The cardiac nerves
affect not only the rate and force of the contraction, but also the con-
162
THE CIRCULATION OF THE BLOOD AND LYMPH
ductivity of the heart. Thus in the frog's heart during stimulation of
the vagus, the contraction passes more slowly, and during stimulation
of the sympathetic more quickly, from auricles to ventricle.
In mammals (and in what follows we shall restrict ourselves chiefly
to the dog, cat, and rabbit, as it is in these animals that the subject
has been most carefully studied) the inhibitory fibres run down the
vagus in the neck and reach the heart by its cardiac branches. They
are derived from the bulbar roots of the spinal accessory, whose inner
branch joins the vagus. The augmentor fibres leave the spinal cord in
the anterior roots of the second and thira thoracic nerves, and possibly
to some extent by the fourth and fifth. Through the corresponding
Fig. 736- — Miniature Myocardiograph (actual size)
(Wiggers). C, light. aluminium. segment capsule
covered by tightly stretched rubber dam, upon
which is cemented an aluminium plate pivoting
upon the chord side of the capsule. The plate
carries a light arm, A, with an eyelet at its end.
A similar arm, A1, is rigidly fastened to the body
of the capsule. The arms can be bent so that
the distance between the eyelets varies from
3 to 25 millimetres, and are connected by
stitches through the eyelets to points on the
auricular surface. The approximation of the
points causes a negative pressure in the cap-
sule, and in the recording capsule (see descrip-
tion of Fig. 31, p. 93) connected with it by the
tube T. Hence, the down-stroke of the^curve
represents contraction, the up-stroke relaxation.
The apparatus is supported by a very', light
spring, S. This enables it to follow varying
degrees of distension and movement of the
auricle without affecting the curve of contrac-
tion. The small mass (less than 2 gm.)'and
high vibration frequency of the instrument
insure a more faithful record of the con-
traction than with older forms.
white rami communicantes they reach the sympathetic cord, and
running up through the stellate ganglion (first thoracic), and the
annulu* of Vieussens, which surrounds the subclavian artery, to the
inferior cervical ganglion, they pass off to the heart by separate ' acce-
lerator ' branches, taking origin either from the annulus or from the
inferior cervical ganglion. Some augmentor fibres are often, if not
always, present in the dog's vago-sympathetic in the neck. It is
especially easy to demonstrate their presence five or six days after
section of the nerve, when the excitability of the inhibitory fibres has
disappeared.
In the dog the vagus and cervical sympathetic are, in the great
majority of cases, contained in a strong common sheath, and pass
THE NERVOUS REGULATION OF THE HEART 163
together through the inferior cervical ganglion. Upon opening this
sheath they may with care be separated, the fibres running in distinct
strands, and not mixed together as in the vago-sympathetic oi the frog.
For some distance below the superior cervical ganglion the cervical
sympathetic is not connected with the vagus, and here the nerves may
be separately stimulated without any artificial isolation. In the rabbit
and some other mammals, including man, the vagus and sympathetic
run a separate course in the neck.
In the mammal, the inhibitory fibres have a smaller direct action
on the ventricle than in the frog. It indeed beats more slowly when
the auricle is slowed, but this is only because in the normally beating
heart the ventricle takes the time from the auricle. The strength
of the ventricular contractions may be not at all diminished, even
when the auricle is beating very feebly during inhibition. When the
auricle is completely stopped, which does not occur so readily as in
the frog, the ventricle also stops for a short time, but soon begins to
beat again with an independent rhythm of its own. In the frog the
ventricle is directly affected by stimulation of the vagus, and the
force of its beats is diminished independently of the inhibitory
effects in the auricles (Practical Exercises, pp. 198, 203).
It has been shown by delicate optical methods of recording the
contraction of small units of the auricular musculature (designated
as the ' fractionate ' contraction by Wiggers) by the method illus-
trated in Fig. 736, that the diminution in the size of the contrac-
tion produced by stimulation of the vagus is essentially due to
depression of the contractility of the muscle, and not, or at any rate
not primarily, to a diminution in its excitability. In other words,
the strength of stimulus needed to elicit a contraction of the muscle
when under the influence of vagus excitation, in the early part of
the inhibition at least, is not increased, whereas the size of the
contraction evoked by a given stimulus is diminished (Fig. 74) .
It is not doubted that the excitation of the vagus does reduce the
excitability of the auricular muscle, but this reduction seems not to
occur so early as the reduction in the amplitude of the beat, and
cannot therefore be responsible for it. The duration of each
(fractionate) contraction is not altered by vagus excitation. It
can likewise be shown that the depression of contractility is not
secondary to the depression of conductivity produced by the vagus.
Finally, it is not dependent upon the slowing of the rhythm which
accompanies the diminution in the contraction of the naturally
beating auricle. For when the auricle is compelled to beat with an
artificial rhythm by applying to it a series of regularly spaced
electrical stimuli at a more rapid rate than the normal rhythm,
stimulation of the vagus still causes reduction in the amplitude of
the contraction without change in the rate (Fig. 74). One other
point is worthy of note. Excitation of the vagus causes an increase
in the size of the first, or occasionally of the first two subsequent
I64
THE CIRCULATION OF THE BLOOD AND LYMPH
contractions of the auricular muscle when the rhythm is slowed,
but not otherwise. It is probable that this is due to the beneficial
influence of the longer period of rest associated with the diminution
in frequency of the beat before the inhibitory action has had time
to cause depression in the amplitude (Wiggers).
Fig. 74. — Influence of the Vagus on the Contraction of the Dog's Right Auricle
The two upper curves are simultaneous records of the contraction of very short
portions of the auricle (so-called fractionate contraction) taken from two
regions, one near the sinus node P, and one far from it, D. The contraction
begins and ends slightly sooner in the proximal than in the distal region.
The lowest curve shows the depressant effect of the vagus excitation mani-
fested when an artificial rhythm (a series of electrical break shocks), which is
not altered by stimulation of the vagus, is substituted for the normal rhythm
sustained by the ' pacemaker.'
The inhibitory fibres, then, influence the heart particularly
through the auricles; they are par excellence auricular nerves. On
the other hand, the accelerantes in all mammals which have been
investigated not only extend to the ventricles, but are even mainly
distributed to them. They are emphatically ventricular fibres, and
THE NERVOUS REGULATION OF THE HEART 165
in accordance with its greater mass the left ventricle receives more
fibres than the right.
Stimulation of the accelerator nerves in the dog causes an
increase in the force of both the auricular and ventricular con-
traction, and as a rule, in addition, some increase in the rate of
the beat.
As to the nature of the physiological linkage between the cardiac
nerves and the muscular tissue of the heart we know but little.
Ganglion-cells lie on the course of the vagus fibres after they
have entered the heart, and although the view has been advocated
that they are simply stations where the inhibitory impulses pass
from medullated to non-medullated fibre s, and where possibly other
Fig. 75- — L ood-Pres-u 2 Tracings: Rabbit. Vagus stimulated at i. Stimulus
siruuger in B than in A (Hiirthle's spring manometer).
anatomical changes and rearrangements occur, they may be inter-
mediate mechanisms which essentially modify the physiological
impulses falling into them. It has been stated that in the dog the
right vagus controls chiefly the rate of the heart, and the left vagus
chiefly the conduction from auricles to ventricles, and the suggestion
has been made that this is because the right vagus has a special
relation to the sino-auricular node, in which impulses are supposed
to arise, and the left vagus a special relation to the auriculo-ven-
tricular node, the upper end of the A-V bundle, the main conduction
system (Cohn and Lewis).
The nervi accelerantes are already non-medullated before they
166 THE CIRCULATION OF THE BLOOD AND LYMPH
reach the heart. The fact that the action of the accelerantes can
be restored by perfusing the heart with a nutrient solution at a
much longer interval after somatic death than the action of the
vagus strengthens the suggestion that ganglion-cells are interposed
on the inhibitory though not on the augmentor path, without,
however, proving of itself that such a difference exists In one
experiment the heart of an anthropoid ape was revived wnen thiee
successive periods — viz., four and a half, twenty-eight and a half,
and fifty-three hours respectively — had elapsed after the death of
the animal, although during the last period the heart had been
twice frozen hard. The vagus was shown to be still capable
of causing some inhibition six hours after death, and the
accelerans some augmentation as late as fifty-three hours after
death (Hering).
In the discussions over the relation of the extrinsic to the intrinsic
cardiac nervous apparatus appeal has frequently been made to the
action of certain poisons on the heart. Thus, after nicotine stimulation
of the vago-sympathetic causes no inhibition of the frog's heart ; it may
cause augmentation. But stimulation of the junction of the sinus and
auricle still causes inhibition. Atropine not only abolishes the inhibi-
tory effect of stimulation of the vagus trunk, but also that of stimula-
tion of the junction of sinus and auricle. Muscarine causes diastolic
arrest in a heart already poisoned with nicotine, but not in a heart
under the influence of atropine. And a heart brought to a standstill by
muscarine can be made to beat again by the application of atropine,
although not by nicotine.
These facts may be explained as follows : Nicotine paralyzes, not the
very ends of the vagus, but the ganglia through which its fibres pass.
Stimulation of the sinus, which is practically stimulation of the vagus
fibres between the ganglion-cells and the muscular fibres, is therefore
effective, although stimulation of the nerve-trunk is not (Langley).
On the other hand, the atropine group paralyzes the nerve-endings
themselves, or interferes with the reception of the inhibitory impulses
by acting on a so-called receptive substance in the muscle (p. 182), so
that neither stimulation of the sinus nor of the nerve-trunk can cause
inhibition. Muscarine, on the contrary, stimulates the vagus fibres
between the nerve-cells and the muscle, or the actual nerve -end ings, or
exerts an inhibitory action on the muscle itself through the appropriate
receptive substance, and thus keeps the heart in a state of permanent
inhibition, which is removed when atropine cuts out the nerve-endings,
or combines with the receptive substance. It is quite in accordance
with this that muscarine has no effect on a heart whose vagus nerves,
as occasionally happens, have no inhibitory power. Pilocarpine has
very much the same action as muscarine.
Stannius' Experiment.— Another series of phenomena, intimately
related to our present subject, have excited, since they were first made
known by Stannius, an enormous amount of discussion. The chief
facts of this classical experiment we have already mentioned (p. 144),
and they are also described in the Practical Exercises (p. 194). They
are easy to verify, but difficult to interpret. The most probable explana-
tion of the standstill caused by the first ligature is that the lower portion
THE NERVOUS REGULATION OF THE HEART
167
of the heart, when cut off from the sinus in which the beat normally
originates, needs some time for the development of its automatic power
to the point at which an independent rhythm can be maintained. The
effects following the second Stannius ligature seem to depend upon the
power of the ventricle to develop and maintain an independent rhythm,
but the contractions are supposed by some to be started by stimulation
of the muscular tissue in the auriculo- ventricular groove by the ligature.
Nature of Inhibition and Augmentation.— So far we have been dis-
cussing the phenomena of inhibition and augmentation as ultimate
facts. We have not attempted to go behind them, nor to ask what it
is that really happens when inhibitory impulses fall into a heart, which
from the first days of embryonic life has gone on beating with a regular
rhythm, and in the space of a second or two bring it to a standstill.
The question cannot fail to press itself upon the mincl of anyone who
has ever witnessed this most beautiful of physiological experiments;
Fig. 76. — Frog's Heart. Sympathetic stimulated (30 mm. between the coils).
Temperature 12°. Marked increase in force. Only auricular tracing rcpro.
duced. Time-trace, two-second intervals.
but as yet there is no answer except ingenious speculations. The most
plausible of these is the trophic theory of Gaskell, who sees in the vagus
a nerve which so acts upon the chemical changes going on in the heart
as to give them a trophic, or anabolic, or constructive turn, and thus to
lessen for the time the destructive changes underlying the muscular
contraction. The augmentor nerves, on the other hand, are supposed
to exert a katabolic influence, and to favour these destructive changes.
And while, according to Gaskell, the natural consequence of inhibition
is a stage of increased efficiency and working power when the inhibition
has passed away, the natural complement of augmentation is a tem-
porary exhaustion. It is very risky, however, to rely, as Gaskell did,
upon a supposed change of sign in the electrical effects during vagus
stimulation, and the only chemical test to which the theory has been
subjected, the comparison of the oxygen consumption of the heart during
and in the absence of inhibition, is adverse to it. The amount of oxygen
used up relatively to the functional activity of the heart as measured by
the product of the frequency of the beat and the maximal increase of pres-
sure caused by it, is not increased by stimulation of the vagus (Rohde).
163 THE CIRCULATION OF THE BLOOD AND LYMPH
Whatever the exact mechanism of augmentation may be, there is
no basis for the statement that the cardio-augmentor nerves have
an action on the heart so fundamentally different from the action of
motor nerves on skeletal muscle that they cannot originate contractions
in a heart entirely at rest. Excitation of the cardio-augmentor nerves
can cause rhythmical contractions in the perfectly quiescent heart of
molluscs, and a sudden and prolonged outburst of beats of great
force in the frog's heart, which has been brought to a standstill by
cautiously heating it to 40° to 43° C. (Practical .Exercises, p. 194) fo'r
a minute or two, or to a considerably lower temperature, for a longer
time (Fig. 77). A similar effect can be obtained on the quiescent
mammalian heart by stimulation of the nervi accelerantes.
28" 5
S30
M 1 1 1 1 m 1 1 ii i 1 1 1 1 1 1 n M i 1 1 1 1 1 1 1 1 1 n 1 1 1 1 1 n rr
jqg. 77. — Effect of Stimulation of Frog's Cardiac Sympathetic during Complete
Standstill of the Heart at 28-5° C. Upper tracing, auricle ; lower, ventricle.
To be read from right to left. Time-trace, two-second intervals.
The Normal Excitation of the Cardiac Nervous Mechanism.—
We have now to inquire how this elaborate nervous mechanism is
normally set into action. And we may say at once, that striking as
are the effects of experimental stimulation of the vagus trunk or the
nervi accelerantes in their course, it is only under exceptional cir-
cumstances that the efferent nerve-fibres, at any rate before they
have entered the heart, can be directly excited in the intact body.
In certain cases the pressure of a tumour or an aneurism on the
nerve-trunks, or, in the case of the accelerators the progress of a
pathological change in the sympathetic ganglia through which the
THE NERVOUS REGULATION OF THE HEART 169
nerve-trunks, or, in the case of the accelerators, the progress of a
pathological change in the sympathetic ganglia through which the
fibres pass, has been thought to bring about by direct stimulation
a slowing or a quickening of the pulse. In some individuals the
vagus has been excited by compressing it against a bony tumour
in the neck; and by compressing the nerve against the vertebral
column it is possible to cause inhibition in many normal persons,
although it ought to be stated that the experiment is not free from
danger. But it is from the cardie-inhibitory and cardio-augmcntor
centres in the medulla oblongata that the impulses which regulate
the activity of the heart are normally discharged. Inhibitory im-
pulses are constantly passing out from the medulla, for section of
both vagi causes almost invariably an increase in the rate of the
heart, at least in mammals, although the increase is less conspicuous
in animals like the rabbit, whose normal pulse-rate is high, than in
animals like the dog, whose pulse-rate is comparatively low. Section
of one vagus usually causes only a comparatively slight increase, for
the other is able of itself to control the heart. It is not certainly
known whether the augmentor centre in like manner discharges a
continuous stream of impulses, or is only roused to occasional activity
by special stimuli. For the results of section of the nervi acceler-
antes, or the extirpation of the inferior cervical and stellate ganglia,
are dubious and conflicting. But if it does exert a tonic influence
on the heart, this is feebler than the tone of the inhibitory centre.
As to the nature of this inhibitory tone, and the manner in which it
is maintained, we know but little. It may be that the chemical
changes in the nerve-cells of the inhibitory centre lead of themselves
to the discharge of impulses along the inhibitory nerves. But there
is some evidence that, in the complete absence of stimulation from
without, the activity of the centre would languish, and perhaps be
ultimately extinguished. For when the greater number of the
afferent impulses have been cut off from the medulla oblongata by
a transverse section carried through its lower border, division of the
vagi produces little effect on the rate of the heart. Also, when the
upper cervical cord and the brain are resuscitated after a period of
anaemia, the return of cardio-inhibitory tone is tardy in comparison
with the return of the truly automatic function of respiration, and
does not seem to precede the opening up of the afferent paths to the
cardio-inhibitory centre. Indeed, reflex inhibition may be produced
at a time when the inhibitory centre has regained none of its tone.
The suggestion is that the normal tone of the centre is largely
dependent upon reflex impulses. Be this as it may, we know that
the activity of the inhibitory centre is profoundly influenced — and
that both in the direction of an increase and of a diminution — by
impulses that fall into it through afferent nerves and by stimuli
directly applied to it. And we may assume that the same is true
of the augmentor centre. The common statement that stimulation
I7<> THE CIRCULATION OF THE BLOOD AND LYMPH
of the central end of one vagus, the other being intact, produces
distinct inhibition does not hold for all mammals. In dogs this is
sometimes the case, but often (under anaesthesia, at any rate) there
is little or no inhibition, or even augmentation. In etherized cats,
on the other hand, some inhibition is always seen. Of all the afferent
fibres of the vagus, the pulmonary fibres produce the most marked
reflex inhibition. The cardiac fibres are much less effective.
These pulmonary nerves also influence the respiratory and vaso-
motor centres. The respiration is temporarily arrested, and the
blood-pressure falls through the dilatation of the small arteries when
they are excited. It is of interest in connection with the subject
of death during the administration of anaesthetics, that the afferent
vagus fibres coming from the alveoli of the lungs can be chemically
stimulated when irritant vapours, such as chloroform, hydrochloric
acid, ammonia, bromine, or formaldehyde are inhaled through a
tracheal cannula, causing reflex arrest of the heart and of the respira-
tory movements and a fall of blood-pressure through vaso-dilatation
(Brodie). At a certain stage in chloroform anaesthesia, before it
has become very deep, comparatively trifling causes may bring
about great and sudden changes in the pulse-rate, owing to the
abnormal mobility of the vagus centre (MacWilliam).
The depressor nerve, a branch of the vagus, which is easily found
in the rabbit as a slender nerve running close to the sympathetic
in the neck, and a little to its inner side, but in the dog is usually
blended with the vago-sympathetic, falls into the same category
^•ith the vagus itself as regards its reflex action on the heart, to
which it bears an important relation. In all mammals some of its
fibres end in the wall of the aorta, but some of them may run down
over the heart to the ventricle. Stimulation of its peripheral end
has no effect, for the fibres in it which influence the circulation are
afferent, not efferent. But excitation of its central end causes a
marked fall of blood- pressure (p. 185), accompanied by, but not
essentially due to, a distinct slowing of the heart. If the animal is
not anaesthetized, there may be signs of pain, and for this reason the
depressor has sometimes been spoken of, somewhat loosely, as the
sensory nerve of the heart. The abdominal sympathetic (of the
frog) also contains afferent fibres, through which reflex inhibition of
the heart can be produced when they are excited mechanically by a
rapid succession of light strokes on the abdomen with the handle
of a scalpel. .
On the other hand, when the central end of an ordinary peripheral
ne/ve like the sciatic or brachial is excited, the common effect is pure
augmentation (Fig. 78), which sometimes develops itself with even
greater suddenness than when the accelerator nerves are directly
stimulated. Occasionally, however, the augmentation is abruptly
followed by a typical vagus action. Here the reflex inhibitory effect
seems to break in upon and cut short the reflex augmertor effect.
THE NERVOUS REGULATION OF THE HEART 171
These examples show that certain afferent nerves are especially
related to the cardio-inhibitory, and others to the car dio- augment or,
centre, or at least that the central connections of some nerves are
such that inhibition is the usual effect of their reflex excitation,
while the opposite is the case with other nerves. But it is im-
probable that the effect of a stream of afferent impulses reaching
the cardiac centres by any given nerve is determined solely by
anatomical relations. The intensity and the nature of the stimulus
seem also to have something to do with the result. For when
ordinary sensory nerves are weakly stimulated, augmentation is
said to be more common than inhibition, and the opposite when
they are strongly stimulated. And while a chemical stimulus, like
the inhaled vapour of chloroform or ammonia, causes in the rabbit
Fig. 78. — Myocardiographic Tracing of Cat's Ventricle. The signal line shows the
point at which the central end of the brachial nerve was stimulated during
resuscitation of the animal after a period of cerebral anaemia. Some augmenta-
tion of the ventricular beat is seen. The notches in the ventricular tracing are
doe to the artificial respiration. Time-trace, seconds.
reflex inhibition of the heart through the fibres of the trigeminus
that confer common sensation on the mucous membrane of the nose,
the mechanical excitation of the sensory nerves of the pharynx
and oesophagus when water is slowly sipped causes acceleration.*
The stimulation of the nerves of special sense is followed sometimes
by the one effect and sometimes by the other. To complete the
catalogue of the nervous channels by which impulses may reach the
cardiac centres in the medulla, we may add that there must be an
extensive connection between them and the cerebral cortex, since
every passing emotion leaves its trace upon the curve of cardiac
action. The so-called ' reflex cardiac death/ which is an occasional
consequence of intense psychical influences (anxiety, fright, etc.),
* In 78 healthy students the average pulse-rate (in the sitting position \
was increased from 73 to 85 per minute by sipping water.
172 THE CIRCULATION OF THE BLOOD AND LYMPH
may be due to the prolonged excitation of the cardio-inhibitory
centre, as well as to the disturbance of other centres in the bulb by
the cortical storm. It is a remarkable fact, too, and one that can
only be explained by such a connection, that although in the vast
majority of individuals the will has no influence whatever on the
rate or force of the heart, except, perhaps, indirectly through the
respiration, some persons have the power, by a voluntary effort, of
markedly accelerating the pulse. In one case of this kind it was
noticed that perspiration broke out on the hands and other parts of
the body when the heart was voluntarily accelerated. A rise of
blood-pressure due to constriction of the vessels has also been
observed. The effort cannot be kept up for more than a short time,
and the pulse-rate quickly goes back to normal. It has been
recently shown that this peculiar power is more common than has
been supposed, and that where it is present in rudiment it can be
cultivated, although it is a dangerous acquisition.
As an example of the direct action on a cardiac centre of a
changed chemical composition of the blood, we may cite the
inhibition produced by injection of bile into a vein and revealed
in the slow pulse of many cases of jaundice ; and as an instance
of the direct action of a physical change, the slowing of the heart
as the blood-pressure rises (p. 188) in asphyxia or on clamping the
aorta. The variation in the pulse-rate associated with changes
in the position of the body, to which we have already referred
(p. 107), is brought about by direct stimulation of the in-
hibitory centre by the increase of blood-pressure in the medulla
oblongata when a person who has been standing assumes the supine,
or even the sitting, posture. But it is also due in part to changes in
the amount of muscular contraction, since muscular exercise causes
acceleration of the heart either reflexly, through afferent muscular
nerves, or by a direct effect of waste products of the metabolism of
the muscles on the cardiac centres in the bulb or on the heart itself
(p. 280).
Theoretically, quickening of the heart might be caused either by
a diminution in the inhibitory tone or by an increase in the activity
of the augmentor centre; and slowing of the heart might be due
either to a diminution in the augmentor tone, if such exists, or to
an increase in the activity of the inhibitory centre. So that it is
not always easy to interpret such results as we have quoted above.
But it would appear that under ordinary conditions the rate of the
heart is mainly regulated by the inhibitory centre, which, within a
considerable range, can produce variations in either direction. The
augmentor mechanism is perhaps merely auxiliary to the inhibitory,
being called into action only in emergencies.
THE NERVOUS REGULATION OF THE BLOODVESSELS 173
SECTION VI. — THE NERVOUS REGULATION OF THE BLOODVESSELS
(VASo-MoTOR NERVES;.
Just as the muscular walls of the heart are governed by two sets
of nerve-fibres, a set which keeps down the rate of working and a
set which may increase it, the muscular walls of the vessels are under
the control of nerves which have the power of diminishing their
calibre (v aso- constrictor) , and of nerves which have the power of
increasing it (vaso-dilator). All nerves that affect the calibre of the
vessels, whether vaso-constrictor or vaso-dilator, are included under
the general name vaso-motor. These vaso-motor nerves, like the
augmentor and inhibitory fibres of the heart, are connected with a
centre or centres, which in turn are in relation with numerous afferent
nerves. It is convenient to distinguish the afferent nerves which
cause on the whole a vaso-constriction and a consequent increase
of arterial pressure as pressor nerves, and those which cause on the
whole vaso-dilatation, with fall of pressure, as depressor nerves,
reserving the terms vaso-constrictor and vaso-dilator for the efferent
portions of the reflex arcs. It is through this reflex mechanism
that the bloodvessels are mainly influenced, although the endings
of the vaso-motor nerves in the smooth muscular fibres or the
muscular fibres themselves are sometimes directly affected by sub-
stances circulating in the blood. Proteoses, for instance, cause by
peripheral action dilatation of the vessels and a fall of blood-pressure
(p. 215); suprarenal extract, or its active principle, adrenalin, or
epinephrin, constriction, with a rise of pressure (pp. 216, 655). Apo-
codeine paralyzes the vaso-motor nerve-endings after a preliminary
stimulation, and now adrenalin causes no constriction. Chryso-
toxin, an active principle of ergot, causes a marked rise of blood-
pressure by stimulating the sympathetic ganglion-cells or the pre-
ganglionic fibres of the vaso-constrictor path. Vaso-motor nerves
control chiefly the small arteries. They have no direct influence on
the capillaries.* Nor has the existence of an effective vaso-motor
regulation of the calibre of the veins, except in the portal system,
been proved up to this time by any clear and unambiguous experi-
ment, although there are grounds on which it has been surmised
that the nervous system does influence the ' tone ' of the whole
venous tract. These grounds will be mentioned in the proper place.
* It is usually taught that the capillaries, being devoid of muscular fibres
in their walls, are not supplied with vaso-motor fibres, and that the only kind
of active contraction of which they are capable is due to a process analogous
to the turgescence of vegetable cells, the thickness of the wall being increased
at the expense of the lumen, while the total cross-section of the vessel remains
unchanged. It has been asserted, however, that a true contraction, in which
both the total section and the lumen are diminished, may be caused in the
capillaries of the nictitating membrane of the frog either by direct stimulation
or by excitation of vaso-motor fibres in the sympathetic (Steinach and Kahn).
174 THE CIRCULATION OF THE BLOOD AND LYMPH
Meanwhile, before describing the distribution of the best-known
tracts of vaso-motor fibres and defining the position of the vaso-
motor centres, we must glance at the methods by which our know-
ledge has been attained.
(1) In translucent parts inspection is sufficient. Paling of the part
indicates constriction; flushing, • dilatation of the small vessels. This
method has been much used, sometimes in conjunction with (2), in such
parts as the balls of the toes of dogs or cats, the ear of the rabbit, the
conjunctiva, the mucous membrane of the mouth and gums, the web of
the frog, the wing of the bat, the intestines, etc.
(2) Observation of changes in the temperature of parts. This method
has been chiefly employed in investigating the vaso-motor nerves of
the limbs, the thermometer bulb being fixed between the toes. In such
peripheral parts the temperature of the blood is normally less than that
of the blood in the internal organs, because the opportunities of cooling
are greater. The effect of a freer circulation of blood (dilatation of the
arteries) is to raise the temperature ; of a more restricted circulation
(constriction of the arteries), to lower it.
(3) Measurement of the blood-pressure. If we measure the arterial
blood-pressure at one point, and find that stimulation of certain nerves
increases it without affecting the action of the heart, we can conclude
that upon the whole the tone of the small vessels has been increased.
But we cannot tell in what region or regions the increase has taken place ;
nor can we tell whether it has not been accompanied by diminution of
tone in other tracts.
But if we measure simultaneously the blood-pressure in the chief
artery and chief vein of a part such as a limb, we can tell from the
changes caused by section or stimulation of nerves whether, and in
what sense, the tone of the small vessels within this area has been altered.
For example, if we found that the lateral pressure in the artery was
diminished, while at the same time it was increased in the vein, we
should know that the ' resistance ' between artery and vein had been
lessened, and that the blood now found its way more readily from the
artery into the vein. If, on the other hand, the venous pressure was
diminished, and the arterial pressure simultaneously increased, we should
have to conclude that the vascular resistance in the part was greater
than before. If the pressure both in artery and vein was increased, we
could not come to any conclusion as to local changes of resistance with-
out knowing how the general blood-pressure had varied.
(4) The measurement of the velocity of the blood in the vessels of
the part. This may be done by the stromuhr or dromograph, or by
allowing the blood to escape from a small vein and measuring the
outflow in a given time, or, without opening the vessels, by estimating
the circulation-time (p. 135). When changes in the general arterial
pressure are eliminated, slowing of the blood-stream through a part
corresponds to increase of vascular resistance in it; increase in the rate
of flow implies diminished vascular resistance. Sometimes the red colour
of the blood issuing from a cut vein, and the visible pulse in the stream,
indicate with certainty that the vessels of the organ have been dilated.
(5) Alterations in the volume of an organ or limb are often taken as
indications of changes in the calibre of the small vessels in it. We
have already seen how these alterations are recorded by means of a
plethysmo graph (p. 128). The brain is enclosed in the skull as in a
natural plethysmograph, and changes in its volume may be registered
by connecting a recording apparatus with a trephine hole.
THE NERVOUS REGULATION OF THE BLOODVESSELS 175
(6) For the separation of the effects of stimulation of vaso-constrictor
and vaso-dilator fibres when they are mingled together, as is the case
in many nerves, advantage is taken of certain differences between them.
For example, the vaso-constrictors lose their excitability sooner than
the vaso-dilators when cut off from the nerve-cells to which they belong.
So that if a nerve is divided, and some days allowed to elapse before
stimulation, only the dilators will be excited. The vaso-dilators are
more sensitive to weak stimuli repeated at long intervals than to strong
and frequent stimuli, and the opposite is true of the constrictors. When
a nerve containing both kinds of fibres is heated, the excitability of
the vaso-constrictors is increased in a greater degree than that of the
dilators; when the nerve is cooled, the dilators preserve their excita-
bility at a temperature at which the constrictors have ceased to respond
to stimulation (Fig. 79).
The Chief Vaso-Motor Nerves. — The first discovery of vaso-motor
nerves was made in the cervical sympathetic. When this nerve is
Fig. 79- — Plethysmograms: Hind-Limb of Cat (after Bowditch and Warren). To be
read from right to left. On the left hand is shown the effect of slow stimulation
ot the sciatic (i per second); on the right hand the effect of rapid stimulation
(64 per second). In the first case the limb swelled owing to excitation of the
vaso-dilators; in the second, it shrank tl/:ough excitation of the vaso-constrictors.
cut, the corresponding side of the head, and especially the ear,
become greatly injected owing to the dilatation of the vessels. This
experiment can be very readily performed on the rabbit, and the
changes are most' easily followed in an albino. The ear on the side
of the cut nerve is redder and hotter than the other; the main
arteries and veins are swollen with blood, and many vessels formerly
invisible come into view. The slow rhythmical changes of calibre,
which in the normal rabbit are very characteristically seen in the
middle artery of the ear, disappear for a time after section of the
sympathetic, although they ultimately again become, visible.
Stimulation of the cephalic end of the cut sympathetic causes a
marked constriction of the vessels and a fall of temperature on the
same side of the head. From these facts we know that the cervical
176 THE CIRCULATION Op THE BLOOD AND LYMPH
sympathetic in mammals contains vasoconstrictor fibres for the
side of the head and ear, and that these fibres are constantly in
action. Certain parts of the eye, and the salivary glands, larynx,
oesophagus, and thyroid gland, are also supplied with vaso- motor
(constrictor) nerves from the cervical sympathetic.
It has been asserted that the cervical sympathetic contains some of
the vasoconstrictor fibres that supply the corresponding half of the
brain and its membranes, but this has been disputed, and some ob-
servers deny that the vessels 01 the brain have any vaso-motor nerves.
Non-medullated nerve-fibies, however, may be seen in and around the
walls of the cerebral and spinal bloodvessels, and it is difficult to believe
that these have not a vaso-motor function, although this has not as
yet been clearly demonstrated by experimental methods.
It has sometimes been argued that we ought not to expect the brain
to be supplied with vaso-motors. For it is enclosed in a rigid box, and
the quantity of blood in it can be increased or diminished only to the
slight extent to which the cerebro-spinal liquid can be displaced into
the vertebral canal. Important changes in the cerebral blood-supply
are therefore brought about, it is said, not by a widening or narrowing
of the cerebral vessels, but by an alteration in the velocity of the blood
in them as a result of a rise or fall of the systemic arterial pressure.
This argument, however, leaves out of account the consideration that
in general the brain does not function as a whole, but that certain
parts of it may often become active and relatively hyperaemic, while
other parts are inactive and relatively anaemic, and that important
changes in the distribution of the blood in the encephalon may be
effected, although the total mass of blood in the organ undergoes little
or no alteration. It is, of course, true that it is not the absolute quantity
of blood in an organ which is a function of its activity, but the rate at
which it is renewed. And it is theoretically possible that an organ at
rest should contain as much blood as when it is active, or even more.
But such cases, if they exist, are certainly rare. The fact that adrenalin
generally constricts the vessels of a perfused brain (Wiggers) is in favour
of the existence of vaso-motors. The retina, which from the stand-
point of development is a portion of the brain, is undoubtedly supplied
with vaso-constrictor fibres which run in the cervical sympathetic.
That the cervical sympathetic contains some dilator fibres is
proved by the fact that stimulation of the cephalic end in the dog
causes flushing of the mucous membrane of the mouth on the same
side. Further, after division of the nerve on one side in the rabbit
it may be observed that when the animal is excited.the vessels of the
ear whose nerve is intact may become still more dilated than those
whose constrictor fibres have been paralyzed. The only explana-
tion is that vaso- dilators are being excited from the central nervous
system.
The vaso-motor fibres of the head run up in the cervical sympa-
thetic, and then pass into various cerebral nerves, of which the fifth
or trigeminus is the most important.
The trigeminus nerve contains vaso-constrictor nerves for various
parts of the eye (conjunctiva, sclerotic, iris), and for the mucous
THE NERVOUS REGULATION OF THE BLOODVESSELS Ifj
membrane of the nose and gums, and section of it is followed by
dilatation of the vessels of these regions. The lingual branch of
the trigeminus supplies vaso-motor fibres to the tongue, and ap-
parently both vaso-constrictor and vaso-dilator.
In some animals — the rabbit, for instance — the ear derives part
of its vaso-motor supply through the great auricular nerve, a branch
of the third cervical nerve, which they reach as grey rami from the
stellate ganglion.
Another great vaso-motor tract, the most influential in the body,
is contained in the splanchnic nerves, which govern the vessels of
many of the abdominal organs. Section of theSvi nerves causes an
immediate and sharp fall of arterial pressure. The intestinal vessels
are dilated and overfilled with blood. As a necessary consequence
of their immense capacity, the rest of the vascular system is under-
filled, and the blood-pressure falls accordingly. Stimulation of the
peripheral end of the splanchnic nerves causes a great rise of blood-
pressure, owing to the constriction of vessels in the intestinal area.
We therefore conclude that in the splanchnics there are vaso-motor
fibres of the constrictor type, and that impulses are constantly
passing down them to maintain the normal tone of the vascular
tract which they command. When the splanchnic nerves are
stimulated, the adrenal glands are so affected that adrenalin passes
out by the veins into the blood-stream. It is clear that if the quan
tity thus liberated were sufficiently large and its liberation suffi-
ciently prompt it might play a part in the rise of pressure (p. 661)
which follows stimulation of the nerves, whether they are excited
directly or in the normal course of events reflexly. But it has not
been demonstrated that this is an effective factor. Dilator fibres
(for the intestines and the kidney, for example) have also been
discovered in the splanchnic nerves, although the constrictors
predominate, and special methods have to be employed for the
detection of the dilators.
The same is true of the nerves of the extremities, which certainly
contain vaso-dilator fibres in addition to vaso-constrictors, although
the difficulty of demonstrating the presence of the former is fully
as great as it is in the splanchnics. For the investigation is com-
plicated by the fact that such nerves as the sciatic supply with
vaso-motor fibres two leading tissues — skin and muscle; and these
are not necessarily affected in the same direction or to the same
extent by stimulation of their vaso-motor fibres. The vaso-con-
strictors under ordinary conditions preponderate, so that section of
the sciatic or the brachial is generally followed by flushing of the
balls of the toes and rise of temperature of the feet, stimulation by
paling and fall of temperature. By taking advantage, however, of
the unequal excitability of dilators and constrictors in a degenerating
nerve, and of the differences between the two kinds of fibres in their
i?3 THE CIRCULATION OF THE BLOOD AND LYMPH
reaction to electrical stimuli (p. 175), it has been shown that vaso-
dilators are also present, and come to the front when the conditions are
rendered favourable for them and unfavourable for the constrictors.
Vaso-motor fibres for the fore-limb (dog) issue from the cord in the
anterior roots of the third to the eleventh dorsal nerves, and for the
hind-limb in the anterior roots of the eleventh dorsal to the third lumbar.
Stimulation of most of these roots causes constriction of the vessels,
but stimulation of the eleventh dorsal may cause dilatation (Bayliss
and Bradford).
The Vaso-Motor Nerves of Muscle. — When the motor nerve of the thin
mylo-hyoid muscle of the frog, which can be observed under the micro-
scope, is cut, and the peripheral end stimulated, the vessels are seen to
dilate distinctly, and this effect is not abolished when contraction of
the muscle is prevented by a dose of curara insufficient to paralyze the
vaso-motor nerves. This indicates the existence in the nerve of vaso-
dilator fibres. But we must be cautious in transferring this result to
ordinary skeletal muscle, for the mylo-hyoid is more closely allied to
the muscles of the tongue than, for example, fo the muscles of the limbs,
and in the mammal the tongue muscles are known to be better supplied
with vaso-dilator fibres than the limb muscles. The average flow of
blood through a mammalian muscle is indeed increased during volun-
tary contraction, and during rhythmically repeated artificial tetaniza-
tion of its motor nerve. The outflow of blood from the main vein of
the levator labii superioris, one of the muscles used in feeding in the
horse, was found to be in one experiment nearly eight times, in another
about seven times, and in a third three and a half times as great during
voluntary work with it (in chewing) as in rest. But as no increase in
the blood-flow through the skeletal muscles of a completely curarized
mammal during excitation of their nerves has ever been satisfactorily
demonstrated, we must conclude that they are very scantily provided
with vaso-dilator fibres or not at all. It is uncertain whether they are
supplied with vaso-constrictors. The undoubted increase in the blood-
flow in contraction may therefore be connected in some way with the
mcjchanical or chemical changes in the muscular fibres themselves.
It has been suggested that the muscular vessels are widened by the
direct action of the acid products of the active muscle, since very dilute
acids (lactic acid, e.g.] cause general dilatation of the small vessels.
-A similar explanation has been extended to the dilatation of the vessels
of the brain during cerebral activity by some of those who deny the
existence of vaso-motor nerves for that organ, but here the evidence
is by no means satisfactory. The vagus has been stated to contain
vaso-constrictor, and the annulus of Vieussens vaso-dilator, fibres for
the coronary arteries of the heart. But this question is far from being
settled. Adrenalin causes dilatation and not constriction of the
coronary vessels. There is some reason to believe that the metabolic
products liberated in the heart-muscle, e.g., carbon dioxide, govern the
changes in the calibre of the coronary arterioles. A close relationship
exists between the output of carbon dioxide and the rate of flow through
the coronary circulation. In asphyxia the flow through the coronary
vessels is notably increased; indeed, it is at its maximum just before
the heart fails altogether, as if an effort were being made to keep the
heart going to the last by making up to it in the quantity of the blood
supplied what it lacks in quality. As this increased flow is seen in the
isolated heart-lung preparation, it has been concluded that metabolites
produced in the cardiac muscle itself cause an increased coronary flow
when increased demands are made on the heart, a local regulative
THE NERVOUS REGULATION OF THE BLOODVESSELS i-tg
mechanism being thus constituted. There is some evidence that carbon
dioxide is not the most potent of these substances.
Vaso-Motor Nerves of the Lungs. — There has been much discussion as
to the course , and even as to the existence , of vaso-motor fibres for the
lungs. The problem is perhaps the most difficult in the whole range of
vaso-motor topography, for the pulmonary circulation is so related to
other vascular tracts, that changes produced in the vessels of distant
organs by the stimulation or section of nerves may affect the quantity
of blood received by the right side of the heart, and therefore the
quantity propelled through the lungs and the pressure in the pulmonary
artery. And changes in the systemic arterial pressure may favour or
hinder the discharge of the left ventricle, and therefore affect the pres-
sure in the left auricle and the pulmonary veins. Nevertheless, evidence
has been obtained from a number of sources that the lungs are supplied
with vaso-constrictor fibres. Plumier, perfusing isolated, ' surviving '
lungs with blood under constant pressure and measuring the outflow,
showed that adrenalin and also stimulation of the annulus of Vieussens
caused great diminution in the flow — that is, constriction of the vessels.
Wiggers also obtained constriction with adrenalin. Fiihner and
Starling, working with a preparation including the heart as well as the
lungs, found that adrenalin caused a rise of pressure in the pulmonary
artery coupled with a fall of pressure in the left auricle, which could
only be due to constriction of the vessels of the lungs. It is assumed
that adrenalin produces vaso-constriction only ia vessels supplied with
vaso-constrictor nerves (p. 655), and that in organs where this substance
does not cause vaso-constriction no such fibres are present. In mam-
mals the vaso-constrictor fibres seem to pass out from the upper half
of the dorsal spinal cord, and some of them can be detected nearer their
destination in the annulus of Vieussens. The vago-sympathetic of the
tortoise contains vaso-constrictors for the lung of the same side (Krogh).
Vaso-Dilator Fibres. — In most of the peripheral nerves these are
mingled with vaso-constrictors; but in certain situations, for an
anatomical reason that will be mentioned presently, nerves exist in
which the only vaso-motor fibres are of the dilator type. Of these,
the most conspicuous examples are the chorda tympani and the
nervi erigentes or pelvic nerves; and, indeed, it was in the chorda
that vaso-dilators were first discovered by Bernard. The chorda
tympani contains vaso-dilator and secretory fibres for the sub-
maxillary and sublingual salivary glands. With the secretory fibres
we have at present nothing to do; and the whole subject will have
to be returned to, and more fully discussed in Chapter VI. But a
most marked vascular change is produced by stimulation of the
peripheral end of the divided chorda tympani nerve. The glands
flush red; more blood is evidently passing through their vessels.
Allowed to escape from a divided vein, the blood is seen to be of a
bright arterial colour and shows a distinct pulse. The small arteries
have been dilated by the action of the vaso-motor fibres in the nerve.
The resistance being thus reduced, the blood passes in a fuller and
more rapid stream through the capillaries into the veins, and on the
way there is not time for it to become completely venous. These
vaso-dilator fibres are not in constant action, for section of the
l8o THE CIRCULATION OF THE BLOOD AND LVMPH
nerve, as a rule, produces little or no change. Vaso-constrictor
fibres pass to the salivary glands from the cervical sympathetic
along the arteries, and stimulation of that nerve causes narrowing of
the vessels and diminution of the blood-flow, sometimes almost to
complete stoppage.
The nervi erigentes are the nerves through which erection of the
penis is caused. When they are divided there is no effect, but
stimulation of the peripheral end causes dilatation of the vessels of
the erectile tissue of the organ, which becomes overfilled with
blood. During stimulation of these nerves, the quantity of blood
flowing from the cut dorsal vein of the penis may be fifteen times
greater than in the absence of stimulation. It spurts out in a strong
stream, and is bi filter than ordinary venous blood (Eckhard).
Stimulation of the peripheral end of the nervus pudendus causes
constriction of the vessels of the penis, so that it contains vaso-
constrictor fibres which are the antagonists of the nervi erigentes.
Vaso-Motor Nerves of Veins. — Like arteries, veins have plexuses
of nerve-fibres in their walls, and contract in response to various
stimuli. In some cases — e.g., in the wing of the bat — rhythmical
contractions of the veins are strikingly displayed, but they do not
depend on the central nervous system, as they persist after section
of the brachial nerves. The existence of vaso-constrictor fibres for
the venules given off in the liver by the portal vein is indicated by the
fact that adrenalin diminishes the blood flow through the organ even
when the hepatic artery has been tied (Burton-Opitz ; Macleod and
Pearce, etc.). Stimulation of the distal end of the hepatic plexus
causes similar effects. The fibres issue from the spinal cord by the
anterior roots of the third to the eleventh dorsal nerves, but chiefly
in the fifth to the ninth dorsal. The arterioles arising from the
hepatic artery have their own vaso-motor supply, which is more com-
plete than that of the portal vessels. When the liver is enclosed in
a plethysmograph, and the central end of an ordinary sensory nerve,
like the sciatic, excited, reflex vaso-constriction takes place in the
portal area, the volume of the organ diminishes, and the blood-pres-
sure rises in the portal vein (Francois-Franck).
The vena portae and its branches are in the physiological sense
arteries rather than veins, since they break up into capillaries, and
it was to be expected that the regulation of the blood-flow in them
would be carried out in the same way as in ordinary arteries, namely,
by means of vaso-motor nerves. But we must not, without special
proof, extend the results obtained in the portal system to ordinary
veins. A certain amount of evidence, however, exists that even
such veins as those of the extremities are supplied, though scantily,
with vaso-constrictor (veno-motor) fibres. After ligation of the
crural artery or aorta, stimulation of the peripheral end of the
sciatic has been seen to cause contraction of short portions of the
superficial veins of the leg.
THE NERVOUS REGULATION OF THE BLOODVESSELS 181
Finally, adrenalin (epinephrin) causes constriction of rings of
' surviving ' veins just as of artery rings, although in correspondence
with the smaller amount of muscular tissue in the former the con-
traction is not so strong. As adrenalin is assumed to act only upon
muscle supplied by sympathetic nerve-fibres (p. 655), this would
seem to indicate the existence of such a supply for veins. The
question is an important one in connection with the regulation of
the filling, and therefore of the discharge, of the heart (Henderson),
but the experimental data are as yet too meagre to justify further
discussion of the matter here.
Course of the Vaso-Motor Nerves. — In the dog the vaso-constrictors
pass out as fine medullated fibres (1-8 to 3-6 p. in diameter) in the
anterior roots of the second dorsal to about the second lumbar nerves.
They proceed by the white rami communicantes to the lateral sym-
pathetic ganglia, where, or in more distal ganglia such as the inferior
mesenteric, they lose their medulla, and their axis-cylinder processes
(p. 851) break up into fibrils that come into close relation with
the nerve-cells of the ganglia. These ganglion-cells in their turn send
off axis-cylinder processes, which, enveloped by a neurilemma, pass as
non-medullated fibres by various routes to their final destination, the
unstriped muscular fibres of the bloodvessels. Their course to the head
has been already described. To the limbs they are distributed in the
great nerves (brachial plexus, sciatic, etc.), which they reach from the
sympathetic ganglia by the grey rami communicantes.
The outflow of vaso-dilator fibies is not restricted to the same portion
of the cord from which the outflow of constrictor fibres takes place.
Their existence is indeed most easily demonstrated in nerves springing
from those regions of the cerebro-spinal axis from which vaso-constrictor
fibres do not arise, and where, therefore, we have not to contend with
the difficulty of interpreting mixed effects. Vaso-dilators for the
external generative organs and the mucous membrane of the lower end
of the rectum pass out as small medullated fibres of the anterior roots
of certain of the sacral nerves (mainly the second and third in the cat)
into the pelvic nerve (nervus erigens). They end in relation with
ganglion-cells in the neighbourhood of the organs which they supply.
The seventh and ninth cranial nerves carry vaso-dilator fibres which
are distributed by way of the lingual and other branches of the fifth
to the salivary glands, the tongue, the mucous membrane of the floor
of the mouth, and part of the soft palate. Those in the lingual, passing
through the chorda tympani, end in gangi ion-cells near the submaxillary
and sublingual glands, and the axons of these cells continue the path
to the vessels of the glands. It is supposed that the vaso-dilators dis-
tributed in other branches of the fifth also have ganglion-cells on their
course. In fact, there is good evidence that every efferent vaso-motor
fibre is interrupted by one, and only by one, ganglion-cell between the
cord and the bloodvessels. The statement has been made that for
certain regions of the body, especially the skin of the limbs, the vaso-
dilator nerves are contained, not in the anterior, but in the posterior
roots. And these, it is claimed, are not aberrant efferent fibres which
have strayed in the course of development into the wrong roots, but true
posterior root-fibres whose cells of origin lie in the spinal ganglia, and
which conduct efferent vaso-dilator impulses in the wrong direction, so
to speak, from the cord to the periphery — ' antidromic ' impulses
(Bayliss).
1 82 THE CIRCULATION OF THE BLOOD AND LYMPH
Effect of Nicotine on Nerve-Cells. — A method which has been found
most fruitful in studying the relations of sympathetic ganglion-cells to
the vaso-motor fibres, as well as to the pilo-motor* and secretory fibres
which in certain situations are so intricately mingled with them, must
here be mentioned. It depends upon the fact that when a suitable
dose of nicotine (10 milligrammes in a cat) is injected into a vein, or a
solution is painted on a ganglion with a brush, the passage of nerve-
impulses through the ganglion is blocked for a time (Langley). The
nerve-fibres peripheral to the ganglion are not affected. The question
whether efferent fibres are connected with nerve-cells between a given
point and their peripheral distribution can, therefore, be answered by
observing whether any effect of stimulation is abolished by nicotine.
If, for instance, the excitation of a nerve caused constriction of certain
bloodvessels before, and has no effect after, the application of nicotine
to a ganglion, its vaso-constrictor fibres, or some of them, must be con-
nected with nerve-cells in that ganglion. Langley has brought forward
evidence that many of the bodies which are commonly supposed to act
upon nerve-endings (as nicotine, curara, atropine, pilocarpine, adrenalin,
etc.) really act upon ' receptive ' substances of the cells in connection
with which the nerve-fibres end. These receptive substances are con-
ceived to be capable of being specifically affected by chemical bodies
and by nervous stimuli, and in their turn to be capable of influencing
the metabolism of the main cell substance on which its function depends.
The receptive substances thus form beyond the histological link of the
nerve-ending a kind of chemical link between the nerve-fibre and the
cell which it supplies.
We have thus traced the vaso-motor nerves from the cerebro-
spinal axis to the bloodvessels which they control ; it still remains
to define the portion of the central nervous system to which these
scattered threads are related, which holds them in its hand and acts
upon them as the needs of the organism may require.
Vaso-Motur Centres. — Now, experiment has shown that there is
one very definite region of the spinal bulb which has a most intimate
relation to the vaso-motor nerves. If while the blood-pressure in
the carotid is being registered, say, in a curarized rabbit, the central
end of a peripheral nerve like the sciatic is stimulated, the pressure
rises so long as the bulb is intact, this rise being largely due to the
reflex constriction of the vessels in the splanchnic area. If a series
of transverse sections be made through the brain, the rise of pressure
caused by stimulation of the sciatic is not affected till the upper
limit of the bulb is almost reached. If the slicing is still carried
downwards, the blood-pressure sinks, and the rise following stimu-
lation of the sciatic becomes less and less. When the medulla has
been cut away to a certain level, only an insignificant rise or none
at all can be obtained. The portion of the medulla the removal of
which exerts an influence on the blood-pressure, and its increase by
reflex stimulation, extends from a level 4 to 5 mm. above the point
of the calamus scriptorius to within I to 2 mm. of the corpora
quadrigemina. Stimulation of the medulla causes a rise, destruc-
* Pilo-motor nerves supply the smooth arrector pili muscles, whose contrac-
tion causes the hair to ' stand on end.'
THE NERVOUS REGULATION OF THE BLOODVESSELS 183
tion of this portion of it a severe fall, of general blood-pressure.
There is evidently in this region a nervous ' centre ' so intimately
related, if not to all the vaso-motor nerves, at least to such very
important tracts as to deserve the name of a vaso-motor centre.
Experiment has shown that this is much the most influential centre,
and it is usually called the chief or general vaso-motor centre. Some
writers prefer to speak of it as the vaso-constrictor centre, since it
is undoubtedly connected with most or all of the vaso-constrictor
paths, and has not been shown to be similarly connected with the
vaso-dilator paths. There is, indeed, not the same solid evidence
for the existence of a general vaso-dilator centre in the bulb as for
the existence of the general vaso-constrictor centre. Yet there are
facts which indicate that the bulbar vaso-motor centre or centres,
when reflexly stimulated, can, and often do, respond not merely by
an increase or a remission of vaso-constrictor tone, but by a simul-
taneous inhibition of vaso-constrictor fibres and excitation of vaso-
dilators leading to a fall of pressure, or by a simultaneous inhibition
of vaso-dilators and excitation of vaso-constrictors leading to a rise
of pressure.
The spinal cells of origin of the pre-ganglionic segments of the
vaso-constrictor paths constitute subordinate centres which either
normally support a certain degree of vascular tone, or come to do so
after the chief vaso-motor centre has been cut off.
Thus, in the frog it is possible to go on destroying more and more
of the cord from above downwards, and still to obtain reflex vaso-
motor effects, as seen in the vessels of the web, by stimulating the
central end of the sciatic nerve. Although these effects indeed
diminish in amount as the destruction of the cord proceeds, yet a
distinct change can be caused when only a small portion of the cord
remains intact.
Similarly, in the mammal evidence has been obtained of the
existence of ' centres ' at various levels of the cord, capable of acting
eventually, if not at once, as vaso-constrictor centres after the loss
of the controlling influence of the bulb. The best example of a
vaso-dilator centre is that situated in the lumbar cord, which controls
the erection of the penis. After total section of the cord at the upper
limit of the lumbar region, erection, which is known to be due to a
reflex dilatation of the arteries of the organ through the nervi eri-
gentes, can still be caused (in dogs) by mechanical stimulation of
the glans penis, so long as the afferent fibres of the reflex arc con-
tained in the nervus pudendus are intact. Destruction of the lumbar
cord abolishes the effect. It is impossible to avoid the conclusion
that a vaso-dilator or erection centre, which is in relation on the
one hand with the nervi erigentes, and on the other with the nervus
pudendus, exists in the lower portion of the spinal cord. Vaso-
motor centres for the hind-limbs have also been located in the
i84 THE CIRCULATION OF THE BLOOD AND LYMPH
same region. When the brain, the bulb, and the upper portion of
the cord have been eliminated by ligation of all the arteries from
which blood can possibly reach them, a sufficient vascular pressure
persists to permit the circulation to go on in the lo\ver portion of
the body for hours. And while section — or freezing (Fig. 80) — of
the cord in the lower cervical region causes a marked fall of pressure,
this r, not permanent if the animal is allowed to survive. Forty-one
days after total section of the cord at the seventh cervical segment
in a dog an arterial pressure of 130 mm. of mercury was found. A
mechanism for the maintenance of vascular tone exists even beyond
the limits of the central nervous system. For when the lower
portion of the cord is completely destroyed, the dilatation of the
vessels of the hind-limbs, which is at first so conspicuous, passes
away after a time, the functions of vaso-motor centres having
perhaps been assumed by the sympathetic ganglia (Goltz and
Ewald). When the lumbo-sacral sympathetic chain is extirpated,
Fig. 80. — Effect on Blood- Pressure of Freezing Spinal Cord (Pike). At i the first
or second dorsal segment of a dog's cord was frozen with liquid air; at 2 and 3
central end of sciatic stimulated without effect on pressure (respectively one and
a half and three minutes after freezing of cord). (Four-fifths of original size.)
there is a further loss of vascular tone in the affected region. But
even this is not irremediable. After a time recovery again occurs,
although it may be more partial and tardy than before. This may
take place either through the intervention of still more peripheral
ganglia, or through the development of a certain tonus by the
muscular fibres of the vessels when abandoned to themselves.
As to the nature of the tone of the general vaso-motor centre, the
same question may be asked which has been already discussed for
the cardio-inhibitory centre. Is it reflex, or does it depend upon
direct excitation of the centre by some constituent of the blood or
lymph, or some substance produced in the centre itself ? The best
answer which can at present be made is that a constant central
excitation by the carbon dioxide formed in the centre or circulating
in the blood is a not unimportant factor in the maintenance of the
vaso-motor tone. A marked diminution in the carbon dioxide
tension of the blood, a condition which is termed ' acapnia,' may
indeed contribute to the severe fall of blood-pressure associated with
THE NERVOUS REGULATION OF THE BLOODVESSELS 185
surgical shock (Henderson). In addition to the direct influence of
carbon dioxide, and possibly of other substances, the arrival of
afferent impulses at the centre seems to play a part in maintaining
that continual discharge of efferent impulses along the vaso-motor
nerves which constitutes its tone. In this regard, the vaso-motor
centre occupies an intermediate position between the respiratory
centre, the most purely automatic, and the cardio-inhibitory centre,
the most purely reflex of the three great bulbar mechanisms.
Of the anatomical relations of the nerve-cells that make up the
bulbar and spinal vaso-motor centres, little more is known than may
be deduced from the physiological facts we have been reciting. It has
been surmised on histological grounds that certain cells of small size
scattered up and down the thoracic and upper lumbar regions of the
cord in the lateral horn (intermedio-lateral tract), and perhaps cropping
out also in the bulb, are vaso-motor cells. There is good evidence that
the pre-ganglionic sympathetic fibres, including the vaso-motor fibres
which we have already discovered emerging from the cord in the spinal
roots, are connected with these cells. And, indeed, there is reason to
believe that the connection is made without the intervention of any
other nerve-cells, and that the axis-cylinders of these vaso-motor fibres
are the axis-cylinder processes of the vaso-motor cells. So that the
simplest efferent path along which vaso-motor impulses can pass may
be considered as built up of two neurons, one with its cell-body in the
cord, and the other in a sympathetic ganglion. Less is known of the
elements which constitute the bulbar centre and of their connections.
But since it would appear that the spinal vaso-motor centres are under
the control of the chief centre in the bulb, it is necessary to suppose
that the axis-cylinder processes of some of the cells of the bulbar centre
come into relation with the spinal vaso-motor cells, and that impulses
passing, let us say, from the bulb to the vessels of the leg, would have
to traverse three neurons (p. 852).
Vaso-Motor Reflexes. — We have already seen that the cardiac
centres are constantly influenced by afferent impulses, and that in
the direction either of augmentation or inhibition. The vaso-motor
centre in the bulb is equally sensitive to such impulses. They
reach it for the most part along the same nerves, and by increasing or
diminishing its tone cause sometimes constriction and sometimes
dilatation of the vessels, the result depending partly upon the ana-
tomical connection of the afferent fibres, but apparently in part also
upon the state of the centre.
Of the afferent nerves that cause vaso-dilatation, the most im-
portant is the depressor, whose reflex inhibitory action on the heart
has been already described. The fall in the arterial pressure is due
chiefly, not to the inhibition of the heart, but to inhibition of the
vaso-constrictor tone of the bulbar vaso-motor centre, combined
with stimulation of vaso-dilator nerves, and consequent general dila-
tation of the arterioles throughout the body. That' the depressor
action involves excitation of vaso-dilators follows from the fact that
vaso-dilatation occurs in the limbs on stimulation of the depressor
after their vaso-constrictor nerves have been cut. Stimulation of the
central end of the depressor may also cause dilatation of the
1 86
THE CIRCULATION OF THE BLOOD AND LYMPH
vessels of the submaxillary gland even on the opposite side, whether
the sympathetic has been divided or not, so long as the chorda
tympani is intact, and this dilatation is not accompanied by a flow
of saliva. Stimulation of the depressor produces its usual result after
section of the vagi. It has been suggested that the function of the
nerve is to act as an automatic check upon the blood-pressure in the
interest both of the heart and the vessels, its terminations in the
aorta or the ventricular wall being mechanically stimulated when the
pressure tends to rise towards the danger limit. In rare cases,
efferent inhibitory fibres for the heart have been found in the depres-
sor of the rabbit.
Many of the peripheral
' nerves contain fibres
whose stimulation is fol-
lowed by dilatation of the
Fig. 81. — Diagram of Depressor
in Rabbit. X, vagus ; SL,
superior laryngeal ; D, de-
pressor. Arrows show course
of impulses.
Fig.82. — Blood- Pressure Tracing: Rabbit. Central
end of depressor stimulated at i ; stimulation
stopped at 2. Time- trace, seconds.
bloodvessels in special regions, usually the areas to which they are
themselves distributed, accompanied by constriction of distant and,
it may be, more extensive vascular tracts. Thus, the usual local effect
of stimulating the afferent fibres of the lowest three thoracic nerves,
in whose anterior roots run the vaso-motor fibres for the kidney, is
a dilatation of the renal vessels (Bradford) , and the usual local effect
of stimulating the infra-orbital or supra-orbital nerve a dilatation
of the external maxillary artery. But the general effect in both
cases is vaso-constriction in other regions of the body, which more
than compensates the local dilatation, so that the arterial blood-
pressure rises. It is not difficult to see that both of these changes
render it easier for the part to obtain an increased supply of blood.
Sometirres the reciprocal relation between vaso-dilatation in one part
of the body and vaso-constriction in another is only apparent. For
example, stimulation of the cut end of the sciatic causes, as we have
already seen, extensive vaso-constriction and a notable rise in the blood-
pressure. The constriction certainly involves the splanchnic area; but
THE NERVOUS REGULATION OF THE BLOODVESSELS i87
superficial parts, as the lips, may be seen to be flushed with blood.
In asphyxia, when the vaso-motor centres are directly stimulated by
the venous blood, this apparent antagonism is still better marked : the
cutaneous vessels are widely dilated and engorged, the face is livid,
but the abdominal organs are pale and bloodless (Heidenhain) . The
blood-pressure rises rapidly, reaches a maximum, and then gradually
falls as the vaso-motor centre becomes paralyzed (Figs. 84 and 85). It
has been shown that in both cases vaso-constriction ot the skin is really
produced as well as vaso-constriction of the internal organs, but the
increased blood-pressure mechanically overcomes the constriction of
the cutaneous vessels.
The kind of stimulus seems to have something to do with the
direction of the reflex vaso-motor change. For while electrical
stimulation of every muscular nerve, even of the very finest twigs
that can be isolated and laid on electrodes, provokes always, whether
the shocks follow each other rapidly or slowly, a rise of general
Fig. 83. — Pressor Effect of Stimulation cf Central End of Vagus in a Cat during
Resuscitation after Cerebral Anaemia. The depressions in the signal line ABC
indicate the duration of three successive excitations of equal strength, sixty-five,
seventy-three, and seventy-nine minutes respectively after restoration of the
circulation. The pressor effect increases as resuscitation proceeds. Later on
the original depressor effect was again obtained. The upper tracing is that of
the artificial respiration. (Two-thirds original size.)
blood-pressure, mechanical stimulation of a muscle, as by kneading
or massage, causes a fall. The condition of the afferent fibres also
exerts an influence. For example, excitation of the central end of a
sciatic nerve that has been cooled is followed by vaso-dilatation
and fall of pressure, the opposite of the ordinary result. These and
similar facts have led to the idea that most afferent nerves contain
two kinds of fibres, whose stimulation can affect the activity of the
vaso-motor centres — ' reflex vaso-constrictor,' or ' pressor ' fibres,
and ' reflex vaso-dilator/ or ' depressor ' fibres. The branch of the
vagus, however, to which the name ' depressor * has been specially
given is usually described as the only peripheral nerve'the excitation
of which is in all circumstances followed by a general diminution of
arterial pressure. But this is not strictly correct, for at an early
period in the resuscitation of the brain after anaemia excitation of
188 THE CIRCULATION OF THE BLOOD AND LYMPH
the rabbit's ' depressor ' causes a slight rise of pressure not followed
by any fall. This, perhaps, indicates the presence in the ' depressor '
of a small number of pressor fibres, which are resuscitated sooner
than the depressor fibres proper. The same phenomenon, only
more marked, may be seen when the central end of the cat's vagus,
containing the depressor fibres, is excited at intervals during resus-
citation (Fig. 83). Or the result may depend upon a change in the
response of the altered vaso-motor centres to impulses reaching
them along the depressor fibres. If specific ' depressor ' fibres exist
in other nerves, they are so mingled with ' pressor ' fibres that their
action is masked when both are stimulated together. The state of
the vaso-motor centre is unquestionably a factor which has some
importance in determining the result of reflex vaso-motor stimula-
tion. For instance, in an animal deeply anaesthetized with chloro-
form or chloral, excitation of pressor fibres (in an ordinary sensory
Fig. 84. — Rise of Blood- Pressure in Asphyxia : Rabbit. Respiration stopped at i.
Interval between 2 and 3 (not reproduced) 44 seconds, during which the blood -
pressure steadily rose. At 4, respiration resumed. Time-trace, seconds.
nerve) causes, not a rise, but a fall of blood-pressure; while in an
animal fully under the influence of strychnine stimulation of the
depressor nerve causes not a fall, but a rise.
The vaso-motor reflexes in man can be conveniently studied by
the calorimetric method described on p. 221. One of the most
important of the vaso-motor reactions is that by which the vessels
of the skin respond to the temperature of the environment so as
to regulate the loss of heat from the body (p. 699). When one
hand, e.g. the left, is immersed in cold water (say at about 8° C.),
the blood-flow in the right is at once reduced owing to reflex vaso-
constriction. Other parts of the body are also affected, but not so
readily as the contra-lateral hand, since the segments of the cord
into which the afferent fibres from a given skin area run are at the
same time the segments from which the efferent vaso-motor fibres
for the symmetrically-placed area on the opposite side of the body
arise. The reflex diminution in the flow persists for a time which
THE NERVOUS REGULATION OF THE BLOODVESSELS t8g
varies with the individual, the external temperature, and other
circumstances, and then as a rule rather suddenly the vaso-con-
striction gives way and the flow begins again to increase, even while
the left hand is still kept in the cold water. When the left hand is
transferred from the cold to warm water (at 43° or 44° C.), the first
effect is a transient diminution in the blood-flow in the right hand.
This soon gives place to an increase (vaso- dilatation). As an ex-
ample, the following table gives the condensed results of three
experiments on two young men. Experiments II. and III. were on
the same man at an interval of three days.
Experi-
ment.
Temperature of —
Duration
of
Observation
in Minutes.
Flow in Grms.
per too c.c.
of Right Hand
per Minute.
Left Hand in —
Room.
Arterial
Blood.
Calorim.
(28-9}
(3i-i
16
12-2
_
I.
J 29-0 1
I 29-0 f
36-6
J3I-7
J3I-2
4
6
6-9
9-9
Cold water.
Cold water still.
U9'iJ
132-3
II
11-6
Warm water.
[24--9
13
IO-I
—
24-2
3i-3
13
5-o
Cold water.
II.
- 23-9 I
23-9
U3-9;
36-0
131-4
31-5
V3I-7
2
3
7
3-4
8-4
15-0
Warm water.
Warm water still.
Warm water still.
(24*1
(3i-6
15
12-4
—
24-4
32-1
5
5-9
Cold water.
ill.
l 24'4 [
36-5
S32-2
5
10-7
Cold water still.
24-4
32-4
3
7-9
Warm water.
124-5;
V32-6
7
17-6
Warm water still.
Such facts enable us to some extent to understand the manner in
which the distribution of the blood is adjusted to the requirements
of the different parts of the body, so that to a certain degree of
approximation no organ has too much, and none too little. The
blood-supply of the organs is always shifting with the calls upon
them. Now, it is the actively-digesting stomach and the actively-
secreting glands of the alimentary tract which must be fed with a
full stream of blood, to supply waste and to carry away absorbed
nutriment. Again, it is the working muscles of the legs or of the
arms that need the chief blood-supply. But wherever the call may
be, the vaso-motor mechanism is able, in health, to answer it by
bringing about a widening of the small arteries of the part which
needs more blood, and a compensatory narrowing of the vessels
of other parts whose needs are not so great.
It is also through the vaso-motor system, and especially by the
action of that portion of it which governs the abdominal vessels, and
too THE CIRCULATION OF THE BLOOD AND LYMPH
of the nerves that regulate the work of the heart, that in animals
to which the upright position is normal (monkey) and in man the
influence of changes of posture on the circulation is almost com-
pletely compensated.* The pressure in the upper part of the
human brachial artery has been measured with a sphygmoman-
ometer, first in the horizontal and then immediately afterwards in
the standing posture, and in health it has been found to remain
practically unchanged (Hill). But if the person was overworked or
out of sorts, the compensation was less complete. It is well known
that in debilitated persons, especially if long confined to bed, the
sudden assumption of the upright position may cause vertigo, and
even syncope, the normal compensatory mechanism being deranged.
In such animals as the rabbit this compensation is totally inefficient.
When a domesticated rabbit, which has been kept in a hutch, is
suspended vertically with the feet down, the blood drains into the
abdominal vessels, syncope speedily ensues, and in a period that
ranges from less than a quarter to three-quarters of an hour the
animal dies in the convulsions of acute cerebral anaemia (Salathe,
Hill). The head- down position has no ill-effects. In wild rabbits,
whose abdominal wall is more tense and elastic, these fatal symp-
toms are not easily produced, and the same is true of cats and dogs.
But in all animals, when the compensation is destroyed, as in
paralysis of the vaso-motor centre by chloroform, the circulation
may be profoundly influenced by the position of the body : elevation
of the head may lead to cerebral anaemia, syncope, and even death ;
elevation of the legs, and particularly the abdomen, may restore the
sinking pulse by filling the heart and the vessels of the brain. If a
chloralized dog be fastened on a board which can be rotated about
a horizontal axis passing under the neck, the blood-pressure in the
carotid artery falls greatly when the animal is made to assume the
vertical position with the head up, and either rises a little or remains
practically unchanged when the head is made to hang down. So
great may the fall of pressure be in the former position that death
may occur if it be long maintained (Practical Exercises, p. 213).
* Two factors may be distinguished in the blood-pressure, the hydrostatic
and the hydrodynamic elements. The hydrostatic portion of the pressure is
due to the weight of the column of blood acting on the vessel; the hydro-
dynamic portion of the pressure is due to the work of the heart. If a dog be
securely fastened to a holder arranged in such a way that the animal can be
placed vertically, with the head up or down, and the mean blood-pressure in
the crural artery be measured in the two positions, there will be a considerable
difference. For when the legs are uppermost the heart has to overcome the
weight of the column of blood rising above it to the crural artery; when the
head is uppermost the action of the heart is reinforced by the weight of the
blood. And if no change were produced in the action of the heart, or in the
general resistance of the vascular path, by the change of position, this differ-
ence would be equal to the pressure of a column of blood twice as high as the
straight-line distance between the cannula and the point of the arterial system
at which the pressure is the same with head up as with head down (indifferent
point).
THE XERVOUS REGULATION OF THE BLOODVESSELS 191
Finally, it is in virtue of the amaxing power of accommodation
possessed by the vascular system, as controlled by the vaso-motor
and cardiac nerves, that so long as these are not disabled the total
quantity of blood may be greatly diminished or greatly increased,
without endangering life, or even causing more than a transient
alteration in the arterial pressure. It is not until at least a quarter
of the blood has been withdrawn that there is any notable effect
on the pressure, for the loss is quickly compensated by an increase
in the activity of the heart and a constriction of the small arteries.
An animal may recover after losing considerably more than half its
blood.* Conversely, the volume of the circulating liquid may be
doubled by the injection of blood or physiological salt solution
without causing death, and increased by 50 per cent, without any
marked increase in the pressure. The excess is promptly stoweH
1 n 1 1 » 1 1 1 1 n i 1 1 1 1 1 1 1
F-g. 85. — Blood- Pressure Tracing from a Dog poisoned with Alcohol.
Therespiratory centre beingparalyzed, respiration stopped, and the
typical rise of blood-pressure in asphyxia took place. The pressure
had again fallen, and total paralysis of the vaso-motor centre was
near at hand, when at A the animal made a single respiratory
movement. The quantity of oxgyen thus taken in was enough to
restore the vaso-motor centre, and the blood-pressure again rose.
repeated five or six times. (Three- fourths original size.)
away in the dilated vessels, especially those of the splanchnic area;
the water passes rapidly into the lymph, and is then more gradually
eliminated by the kidneys.
From these facts we can deduce the practical lesson, that blood-
letting, unless fairly copious, is useless as a means of lowering the
general arterial pressure, while it need not be feared that transfusion
of a considerable quantity of blood, or of salt solution, in cases of
severe haemorrhage, will dangerously increase the pressure. And
from the physiological point of view the term ' haemorrhage ' includes
more than it does in its ordinary sense. For as dirt to the sani-
tarian is ' matter in the wrong place,' haemorrhage to the physiolo-
gist is blood in the wrong place. Not a drop of blood may be lost
from the body, and yet death may occur from haemorrhage into the
pleural or the abdominal cavity, into the stomach or intestines.
Not only so, but a man may bleed to death into his own blood-
* It is not usually possible to obtain quite two-thirds of the total blood by
bleeding a dog from a large artery. In seven dogs bled from the carotid,
the ratio of the weight of the blood obtained to the body-weight was
i : 24-7. i : zi"j. i : 22-7. i : 20-6, i : 18-6. i : 16, i : 13-5. In the last case, the
blood clotte I with abnormal slo .vnes ;. and the animal died in a few minutes.
IQi THE CIRCULATION OF TH£ BLOOD A\'D LYMPH
vessels ; in surgical (also sometimes called traumatic or vascular)
shock, it would appear that the blood which ought to be circulating
through the brain, heart, and lungs may stagnate in the dilated veins.
The essential nature of ' vascular ' shock, which should be dis-
tinguished from the spinal shock described in Chapter XVI. is so
little understood, in spite of the large amount of work devoted to
the subject, that it would not be profitable to discuss it here. It may
be remarked, however, that there is no reason to suppose that ex-
haustion orlossof sensitiveness of the vaso-mo tor centre is concerned.
While an undue proportion of the blood is accumulated in the great
veins, the arterioles and capillaries of the splanchnic area, like those
of the skin, are contracted and contain less blood than normal (Lyon,
Janeway and Jackson, etc.).
SECTION VII. — THE LYMPHATIC CIRCULATION.
As has already been stated, some of the constituents of the blood,
instead of passing back to the heart from the capillaries along the veins,
find their way by a much more tedious route along the lymphatics.
The blood capillaries are everywhere in very intimate relation with
lymph capillaries, which, completely lined with epithelioid cells, lie in
irregular spaces in the connective-tissue that everywhere accompanies
and supports the bloodvessels. The constituents of the blood-plasma
are filtered through, or secreted by the capillary walls into these lymph
spaces, and mingling there with waste products discharged by the cells
of the tissues, form the liquid known as tissue liquid or tissue lymph.
From the tissue liquid the lymph capillaries take up the constituents
of the ' lymphatic ' lymph, which then passes into larger lymphatic
vessels, with lymphatic glands at intervals on their course. These fall
into still larger trunks, and finally the greater part of the lymph reaches
the blood again by the thoracic duct, which opens into the venous
system at the junction of the left subclavian and internal jugular veins.
The lymph from the right side of the head and neck, the right extremity,
and the right side of the thorax, with its viscera, is collected by the
right lymphatic duct, which opens at the junction of the right sub-
clavian and internal jugular veins. The openings of both ducts are
guarded by semilunar valves, which prevent the reflux of blood from
the veins. Serous cavities like the pleural sacs, although differing
from ordinary lymph spaces, are connected through small opening',
called stomata, with lymphatic vessels.
The rate of flow of the lymph in the thoracic duct is very small com-
pared with that of the blood in the arteries — only about 4 mm. per
second, according to one observer. Nevertheless, a substance injected
into the blood can be detected in the lymph of the duct in four to seven
minutes (Tschirwinsky) . The factors which contribute to the main-
tenance of the lymph flow are :
(1) The pressure under which it passes from the blood capillaries into
the lymph spaces and from the lymph spaces into the lymph capillaries.
The pressure in the thoracic duct of a horse may be as high as 12 mm.
of mercury; in the dog it may be less than i mm. The difference is
probably due, in part at least, to a difference in the experimental con-
ditions, dogs being usually anaesthetized for such measurements, horses
not. The pressure in the lymph capillaries must, of course, be higher
than in the thoracic duct — how much higher we do not know.
(2) The contraction of muscles increases the pressure of the lymph
by compressing the channels in which it is contained, and the valves
193
with which the lymphatics are even more richly provided than the
veins, hinder a backward and favour an onward flow. The contractions
of the intestines, and especially of the villi, aid the movement of
the chyle. By the contraction of the diaphragm, substances may
be sucked from the peritoneal cavity into the lymphatics of its
central tendon, through the stomata in the serous layer with which
its lower surface is clad. It is even possible by passive movements of
the diaphragm in a dead rabbit to inject its lymphatics with a coloured
liquid placed on its peritoneal surface. Passive movements of the
limbs and massage of the muscles are also known to hasten the sluggish
current of the lymph, and are sometimes employed with this object in
the treatment of disease.
(3) The movements of respiration aid the flow. At every inspiration
the pressure in the great veins near the heart becomes negative, and
lymph is sucked into them (p. 226).
(4) In some animals rhythmically - contracting muscular sacs or
hearts exist on the course of the lymphatic circulation. The frog has
two pairs, an anterior and a posterior, of these lymph hearts, which
pulsate, although not with any great regularity, at an average rate ol
sixty to seventy beats a minute, and are governed by motor and inhibi-
tory centres situated in the spinal cord. The beat is not directly ini-
tiated from the cord, but the tonic influence of the cord is necessary in
order that the lymph hearts may continue to beat (Tschermak). Such
hearts are also found in reptiles. It is possible that in animals without
localized lymph hearts the smooth muscle, which is so conspicuous an
element in the walls of the lymphatic vessels, may aid the flow by
rhythmical contractions.
PRACTICAL EXERCISES ON CHAPTER III.
i. Microscopic Examination of the Circulating Blood.— (i) Take a
tadpole and lay it on a glass slide. Cover the tail with a large cover-
slip, and examine it with the low power (Leitz, oc. III., obj-. 3).
Generally the tail will stick so closely to the slide, and the animal will
move so little, that a sufficiently good view of the circulation can be
obtained. If there is any trouble, destroy the brain with a needle.
Observe the current of the blood in the arteries, capillaries and veins.
An artery may be easily distinguished from a vein by looking for a
place at which the vessel bifurcates. In veins the blood flows in the
two branches of the fork towards the point of bifurcation, in arteries
away from it. Sketch a part of a field.
To Pith a Frog. — Wrap the animal in a towel, bend the head forwards
with the index-finger of one hand, feel with the other for the depression
at the junction of the head and backbone, and push a narrow-bladed
knife right down in the middle line. The spinal cord will thus be
divided with little bleeding. Now push into the cavity of the skull a
piece of pointed lucifer match. The brain will thus be destroyed. The
spinal cord can be destroyed by passing a blunt needle down inside the
vertebral canal.
(2) Take a frog and pith its brain only, inserting a match to prevent
bleeding. Pin the frog on a plate of cork into one end of which a
glass slide has been fastened with sealing-wax. Lay the web of one
of the hind-legs on the glass and gently separate two of the toes, if
necessary by threads attached to them and secured to the cork plate.
Put the plate on the microscope -stage and fasten by the clips (see
pp. 15, 118).
(3) After the normal circulation has been studied thoroughly put a
very small drop of tincture of cantharides on the portion of the web
13
194 THE CIRCULATION OF THE BLOOD AND LVMPti
which is in the field of the microscope, using a fine pipette. Observe
the process of inflammation, including stasis and diapedesis (p. 61).
2. Anatomy of the Frog's Heart. — Expose the heart of a pithed frog
by pinching up the skin over the abdomen in the middle line, dividing
it with scissors up to the lower jaw, and then cutting through the
abdominal muscles and the bony pectoral girdle. The external ab-
dominal vein, which will be observed on reflecting the skin, can be
easily avoided. The heart ^yill now be seen enclosed in a thin mem-
brane, the pericardium, which should be grasped with fine-pointed
forceps and freely divided. Connecting the posterior surface of the
heart and the pericardium is a slender band of connective tissue, the
fraenum. A silk ligature may be passed round this with a threaded
curved needle, or curved fine-pointed forceps; and tied, and then the
fraenum may be divided posterior to the ligature. The anatomical
arrangement of the various parts of the heart should now be studied.
Note the single ventricle with the bulbus arteriosus, the two auricles,
and the sinus venosus, turning the heart over to see the latter by means
of the ligature. Observe the whitish crescent at the junction of the
sinus venosus and the right auricle (Fig. 86).
3. The Beat of the Heart. — Note that the auricles beat first, and
then the ventricle. The ventricle becomes smaller and paler during
its systole, and blushes
red during diastole.
Count the number of
beats of the heart in a
minute. Now excise the
heart, lifting it by means
of the ligature, and tak-
ing care to cut wide of the
sinus venosus. Place the
heart in a small porce-
lain capsule on a little
blotting - paper moist -
ened with physiological
salt solution.* Observe
that it goes on beating.
Put a little ice or snow
in contact with the heart
and count the number of
beats in a minute. The
rate is greatly dimin-
ished. Now remove the ice and blotting-paper, cover the heart with
the salt solution, and heat, noting the temperature with a thermometer.
Observe that the heart beats faster and faster as the temperature rises.
At 40° to 43° C. it stops beating in diastole (heat standstill). Now at
once pour off the heated liquid, and run in some cold salt solution. The
heart will begin to beat again.
4. Cut off the apex of the ventricle a little below the auriculo-
ventricular groove. The auricles, with the attached portions of the
ventricle, go on beating. The apex does not contract spontaneously,
but can be made to beat by stimulating it mechanically (by pricking
it with a needle) or electrically. Divide the still contracting portion
of the heart by a longitudinal incision. The two halves go on beating.
5. Heart Tracings. — (i) Fasten a myograph-plate (Fig. 87) on a
stand. Take a long light lever, consisting of a straw or a piece of
* For frog's tissues this should be 0-7 to 0-75 per cent, sodium chloride
solution, for mammalian tissues a little stronger (about 0-9 per aent.).
Fig. 86. — Frog's Heart with Stannius* ligatures in
Position (Cyon). Anterior surface of heart shown
on the left, posterior surface on the right, a, right
auricle; 6, left auricle; c, ventricle; d, bulbus arte-
riosus; e, f, aortae; g, sinus venosus.
PRACTICAL EXERCISES
195
Fig. 87. — Arrangement for obtaining a
Heart Tracing from a Frog.
thin chip, armed at one end with a writing-point of parchment-paper,
supported near the other end by a horizontal axis, and pierced not
far from the axis by a needle carrying on its point a small piece of
cork or a ball of sealing-wax.
A counterpoise is adjusted on the short arm of the lever in the form
of a small leaden weight. Cover a drum with glazed paper and smoke
it. The paper must be put on so tightly that it will not slip.
To smoke the drum, hold it by the spindle in both hands over
a fish-tail burner, depress the drum in the flame, and rotate
rapidly. The speed of the drum can be varied by putting in
or taking out a small vane. Arrange an electro-magnetic time-
marker for writing seconds (Fig.
88). Pith a frog" (brain only),
expose the heart, and put under
it a cover-slip to give it support.
Pin the frog on the myograph-
plate, and adjust the foot of the
lever so that it rests on the ven-
tricle or the auriculo-ventricular
junction. Bring the writing-point
of the lever and that of the time-
marker vertically under each other
on the surface of the drum. Set off
the drum at the slow speed (say,
a centimetre a second) . When the
lever rests on the auriculo-ventricular junction, the part of the tracing
corresponding to the contraction of the heart will be broken into two
portions, representing
the systole of the auri-
cles and ventricle re-
spectively. Cut the
paper off the drum
with a knife (keeping
the back of the knife
to the drum to avoid
scoring it) and carry
it to the varnishing-
trough, holding the
tracing by the ends
with both hands,
smoked side up. Im-
merse the middle of it
in the varnish, draw
first one end and then
the other through the
varnish, let it drip
for a minute into the
trough, and fasten it
up with a pin to dry.
Fig. 88. — Electro - Magnetic Time - Marker connected
with Metronome. The pendulum of the metro-
nome carries a wire which closes the circuit when
it dips into either of the mercury cups, Hg.
(2) Heart Tracing,
with Simultaneous Re-
cord of Auricular and Ventricular Contractions. — (a) For this purpose two
levers may be arranged, one resting on the auricle, the other on the ven-
tricle, the writing-points being placed in the same vertical straight line
on the drum. A convenient form of apparatus is shown in Fig. 89.
(b) Gaskeirs Method (a modification of). — Attach a silk ligature to
the very apex of the ventricle. Divide the frsenum, cut the aorta
196
THE CIRCULATION OF THE BLOOD AND LYMPH
across close to the bulbus, pinch up a tiny portion of the auricle and
ligature it. Remove the intestines, liver, lungs, etc., care being taken
in cutting away the liver not to injure the sinus. Then remove the
lower jaw, and cut away the whole of the body except the head, part
of the oesophagus, and the tissue connecting it with the heart. Fix
the head in a clamp sliding on an ordinary stand. The heart is held
at the auriculo-ventricular junction in a Gaskell's clamp supported on
a separate stand. The thread connected with the ventricle is brought
round a pulley and attached to a lever above the heart. The auricle
is connected with another lever. The writing-points of the two levers
are arranged in a vertical line on the drum. The small pulley must
be oiled from time to time to lessen the friction (Fig. 90).
If tortoises or turtles are available, the much larger heart of these
animals may be used for Experiments 5 (2) (a) and (&). The animal
having been killed by cutting off its head, the ventral portion of the
carapace is detachc d by the saw. The pericardium can now be slit
open, and the pads of the levers arranged on auricles and ventricle
fad fo rest an Aurtcte
/ . Pad to rest on Ventrtcte
Fig. 89. — Apparatus for obtaining a Simultaneous Tracing of Auricular and
Ventricular Contractions.
respectively, as in Experiment 5 (2) (a), without further disturbing
the heart. Or the heart may be removed, together with the upper
portion of the body, the pericardium opened, and the liver cut away.1
The aortic trunk is then divided, and the portion of it attached to
the heart grasped by a small forceps clamp. Fine silk ligatures are:
attached to the apex of the ventricle and the top of the right auricle..
The vagus nerves are exposed in the neck, ligated, and divided. The
upper portion of the body is supported on a stand. The forceps grasp-
ing the aorta is fixed in an ordinary holder, and the threads are attached
to the levers, as in Experiment 5 (2) (b).
With the vagi, Experiment 7 may be performed. It must be remem-
bered that the activity of the two vagi is unequal in the tortoise, the
right being the more active.
6. Dissection of the Vagus and Cardiac Sympathetic Nerves in the
Frog. — (i) Put the tissues in the region of the neck on the stretch by
passing into the gullet a narrow test-tube or a thick glass rod moistened
with water, and by pinning apart the anterior limbs. Expose the heart
PRACTICAL EXERCISES
197
by cutting through the pectoral girdle in the way described in 2 (p. 194).
On clearing away a little connective tissue and muscle with a seeker,
three large nerves will come into view. The upper is the glosso-
pharyngeal, the lower the hypoglossal; the vagus crosses diagonally
between them (Fig. 91). Above the vagus trunk, running parallel to
it, and separated from it
by a thin muscle and a
bloodvessel (the carotid
artery), lies its laryngeal
branch. The vagus should
be traced up to the gang-
lion situated on it near its
exit from the skull.
(2) Then cut away the
lower jaw, dividing and
reflecting the membrane
covering the roof of the
mouth. At the junction
of the skull and the back-
bone will be seen on each
side the levator anguli
scapulae muscle (Fig. 92).
Remove this muscle care-
fully with fine forceps.
Clear away a little con-
nective tissue lying just
over the upper cervical
vertebrae, and the sym-
pathetic chain, with its
ganglia, will be seen. Pass
a fine silk thread beneath
the sympathetic about the
level of the large brachial
nerve, by means of a
sewing-needle which has
been slightly bent in a
flame and fastened in a
handle. Tie the ligature,
divide the sympathetic be-
low it, and isolate it care-
fully with fine scissors up
to its junction with the
vagus ganglion.
Batteries — To set up a
Daniett Cell. — Fill the por-
ous pot (Fig. 230, p. 724),
previously well soaked in
water, with dilute sulph-
uric acid (i part of com-
mercial acid to 10 or 15
parts of water) to within
i£ inches of the brim, and place in it the piece of amalgamated zinc. If
the zinc is not properly amalgamated, leave it in the pot fo'r a minute or
two to clean its surface. Then lift it out, pour over it a little mercury,
and rub the mercury thoroughly over it with a cloth. Put the pot
into the outer vessel, which contains the copper plate, and is filled
with a saturated solution of sulphate of copper, with some undissolved
B
— B
Fig. 90. — Arrangement for recording Auricular
and Ventricular Contractions (and studying the
Influence of Temperature of the Heart). C,
clamp holding the heart at the auriculo-ven-
tricular groove; P, pulley round which a thread
attached to the apex of the ventricle passes to
the lever L'; L, lever connected with auricle.
(The rest of the arrangement is for studying the
influence of temperature on the heart and its
nerves, G being a vessel filled with physiological
salt solution in which the heart is immersed; R,
an inflow tube from a reservoir containing salt
solution at the temperature required; O', an out-
flow tube by which G may be emptied into the
beaker B'; O, a tube passing to the beaker B to
prevent overflow from G; T, a thermometer.)
198
THE CIRCULATION OF THE BLOOD AND LYMPH
crystals to keep it saturated. After using the Daniell, it must always
be taken down. The outer pot is left with the copper plate and the
sulphate solution in it. The zinc is washed and brushed bright. The
sulphuric acid is poured into the stock bottle, and the porous pot put
into a large jar of water to soak.
The Bichromate Cell contains only one liquid — a mixture of i part
of sulphuric acid with 4 parts of a 10 per cent, solution of potassium
bichromate. In this is placed one, or in some forms two, carbon
plates and a plate of amalgamated zinc. After using the battery, take
the zinc out of the liquid.
The Leclanche battery consists of a porous pot filled with a mixture
of manganese dioxide and carbon packed around a carbon plate, which
forms the positive pole. The pot stands in an outer jar of glass filled
with a saturated solution of ammonium chloride, into which dips an
amalgamated zinc rod, which constitutes the negative pole. Various
forms of dry batteries can be conveniently used for running indue tion-
coils or time-markers, but are not
rrvi
LqryngeaL
branch of
'
adapted for yielding constant cur-
rents of long duration.
7. Stimulation of the Vagus in
the Frog. — Make the same arrange-
ments as in 5 (i) (p. 195), but in
addition set up an induction
machine arranged for an inter-
rupted current (Fig. 93), with a
Daniell, a bichromate, a Leclanche,
or a dry cell in the primary circuit,
which should also include a simple
key. Insert a short-circuiting key
in the secondary circuit. Attach
the electrodes to the short-circuit-
ing key, push the secondary coil
up towards the primary until the
shocks are distinctly felt on the
tongue when the Neef 's hammer is
set going and the short-circuiting
key opened. Pith the brain of a
frog, expose the heart, dissect out
the vagus on one side, ligature it
as high up as possible, and divide
above the ligature. Fasten the electrodes on the cork plate by means
of an indiarubber band, and lay the vagus on them. Set the drum
off (at slow speed). After a dozen heart -beats have been recorded,
stimulate the vagus for two or three seconds by opening the short-
circuiting key. If the nerve is active, the heart will be slowed,
weakened, or stopped. In the last case the lever will trace an unbroken
straight line ; but even if the stimulation is continued the beats will
again begin.
8. Stimulation of the Junction of the Sinus and Auricles. — After a
sufficient number of the observations described in 7 have been taken
with varying time and strength of stimulation, take the writing-points
off the drum, apply the electrodes directly to the crescent at the junc-
tion of the sinus venosus with the right auricle, and stimulate. The
heart will be affected very much in the same way as by stimulation of
the vagus, except that during the actual stimulation its beats may be
quickened and the inhibition may only begin after the electrodes have
been removed (Fig. 70, p. 158)'.
Fig. 91. — The Relations of the Vagus
in the Frog.
9- Effect of Muscarine (or Pilocarpine), and Atropine. — Paint on the
sinus venosus with a small camel's-hair brush a very dilute solution oi
muscarine (or of pilocarpine). The heart will soon be seen to beat
more slowly, and will ultimately stop in diastole. Now apply a dilute
solution of sulphate of atropine to the sinus. The heart will again
begin to beat. Stimulation of the vagus will now cause no inhibition
of the heart, because its endings have been paralyzed by atropine.
(Muscarine or pilocarpine has also been applied to the heart, but it
could be shown by a separate experiment that atropine by itself has
the same effect on the vagus endings — p. 16 .)
10. Stannius' Experiment. — Pith a frog. Expose the heart in the
way described under 2 (p. 194). Ligature the frsenum with a fine silk
thread, and use the thread to manipulate the heart. With a curved
needle pass a moistened silk thread between the aorta and the superior
vena cava, and tie it round the
junction of the sinus and right
auricle (Fig. 86). The auricles
and ventricle stop beating as
soon as the ligature is tightened.
The sinus venosus goes on beat-
ing. Now separate the ven-
tricle from the rest of the heart
by an incision through the
auriculo-ventricular groove, or
tie a second ligature in the
groove. The ventricle begins
to beat again, the auricle re-
maining quiescent in diastole
(p. 166). Occasionally both
auricle and ventricle, or only
the auricle, may begin to beat.
n. Stimulation of Cardiac
Sympathetic Fibres in the Frog
— (i) In the vago-sympathetic
after the inhibitory fibres have
been cut out by atropine. —
Arrange everything as in 7
(p. 198). Assure yourself, by
£AS
Fig. 92. — Relation of the Sympathetic to
the Vagus in the Frog (after Gaskell).
Sym, sympathetic chain ; G, ganglion of
the vagus; VS, vago-sympathetic; GP,
glosso-pharyngeal nerve; LAS, levator
anguli scapulae muscle ; SA, subclavian
artery; A, descending aorta; V, vertebral
column; OC, occipital part of skull; 1-4,
spinal nerves.
stimulating the vagus, that it
inhibits the heart, and take
a tracing during stimulation.
Then paint a dilute solution
of atropine on the sinus.
Stimulation of the vagus, which is really the vago-sympathetic (see
Fig. 92), will now cause, not inhibition, but augmentation (increase
in rate or force, or both), since the endings of the inhibitory fibres have
been paralyzed by atropine. The strength of the stimulating current
required to bring out a typical augmentor effect is greater than that
needed to stimulate the inhibitory fibres. Take a tracing to show
augmentation produced by stimulating the nerve.
(2) By direct stimulation of the cervical sympathetic. — Make the same
arrangements as in n (i), but, instead of isolating the vagus, dissect
out the sympathetic on one side in the manner described in -6 (2) (p. 197),
and do not apply atropine to the heart. Lay the upper (cephalic) end
of the sympathetic on very fine and well-insulated electrodes, and
stimulate (Fig. 76, p. 167). (To insulate electrodes the points may be
covered with melted paraffin. When the paraffin has cooled, a narrow
200
THE CIRCULATION OF THE BLOOD AND LYMPH
groove, just sufficient to lay bare the wires on the upper side, is made
in it, and the nerve is laid in this groove.)
Experiments 7, n (i) and n (2) will be rendered more exact by
connecting a second electro-magnetic signal with a Pohl's commutator
without cross-wires (Fig. 94), in such a way that the circuit is inter-
rupted at the instant when stimulation begins.
12. The Action of Inorganic Salts on Heart- Muscle. — Expose and
remove the heart of a tortoise or turtle (p. 196). Cut off the apical two-
thirds of the ventricle by an incision parallel to the auriculo-ventricular
groove. By a second parallel cut remove a ring of tissue 2 or 3 milli-
metres wide from the upper end of this portion of the ventricle. Divide
the ring at opposite ends of a diameter, so as to form two strips. Tie
a fine silk thread to each end of one strip. Attach one of the threads
to the short limb of a glass rod bent at right angles, so that it can be
immersed at will in a beaker. The other end of the rod is fixed in a
holder sliding on a stand. Attach the second thread to the short arm
Fig- ?3- — Arrangement of Induction Machine for Tetanus. B, battery; K, simple
key ; P, primary coil ; S, secondary coil ; A, C, binding screws to be connected
with battery 46r single shocks; F, G, binding screws for tetanizing current; N,
Neef's hammery D, short-circuiting key in secondary; E, electrodes. D and E
are drawn to a much larger scale than the rest of the figure.
of a counterpoised lever arranged to write on a slowly-moving drum.
If the strip is still beating, wait till the contractions have ceased ; then
(1) Immerse the strip in a beaker filled with o'y per cent, solution of
sodium chloride. After a time it begins to beat rhythmically. The
contractions become rapidly stronger, and then after a while diminish,
and gradually cease. The tone or tonus of the strip is diminished by
the solution.
(2) Arrange the other strip in the same way, and immerse it in a
solution of calcium chloride (about I per cent.) isotonic with the sodium
chloride solution used in (i). If the strip is contracting, the contrac-
tions will cease. Rhythmical contractions will not appear as in the
sodium chloride solution. The tone of the strip may be increased.
(3) Remove most of the calcium chloride solution from the beaker,
and fill it up with 0-7 per cent, sodium chloride solution. The rhythmi-
cal contractions will appear after a longer or shorter latent period, and
will be stronger and last for a longer time than in the sodium chloride
solution alone.
(4) Immerse a fresh strip in a solution containing sodium chloride
PRACTICAL EXERCISES aol
(o-7 per cent.), calcium chloride (o-o25 per cent.), and potassium
chloride (0-03 per cent.) (a modified Ringer's solution). A longer
series of rhythmical contractions will be obtained than in either (i)
or (3). That this is not due to the potassium chloride acting alone
can be shown by immersing a strip in a solution of potassium chloride
(about o '9 per cent.) isotonic with the sodium chloride solution used
in (i). No contractions will be caused.
13. The Action of the Mammalian Heart. — Inject under the skin of a
dog (preferably a small one) i c.c. of a 2 per cent, solution of morphine
hydrochlorate for every kilo of body-weight. As soon as the morphine
has taken effect (in 15 to 30 minutes, but better after an hour), fasten
the animal back down on a holder (as in Fig. 135, p. 301), pushing the
mouth-pin behind the canine teeth and screwing the nut home.* In
the meantime select a tracheal cannulaf of suitable size, and get ready
instruments for dissection — one or two pairs of artery-forceps, a pair
of artery-clamps (bulldog pattern), two or three glass cannuloc of
'B'
Fig- 94- — Arrangement for recording the Beginning and End of Stimulation. C.
Pohl's commutator without cross-wires; B, battery in circuit of primary coil P;
B', battery in circuit of electro-magnetic signal T; K, simple key in primary
circuit; S, secondary coil. When the bridge of the commutator is tilted into
the position shown in the figure, the primary circuit is closed and the circuit of
the signal broken.
various sizes for bloodvessels, ten strong waxed ligatures, sponges,
hot water, a towel or two, and a pair of bellows to be connected with
the tracheal cannula when the chest is opened. Arrange an induction -
* A simple but efficient and convenient holder for a dog may be easily
constructed as follows: Take a board of the length required (2^ to 5 feet,
according to the size of the dog) . At one end fasten two short upright wooden
pins, with a clear space of 4 to 6 inches between them. These are pierced
from side to side with four or five holes at different heights. An iron pin passes
behind the canine teeth of the animal through two corresponding holes in the
uprights, and the muzzle is tied over this by a cord which secures the head.
For a large dog an upper pair of holes is used, for a small dog a lower pair.
The feet are fastened by cords to staples inserted into the sides of the board,
the fore-legs being drawn tailwards for all operations on the neck or head,
headwards for operations on the thorax. A rabbit-holder can be made in
exactly the same way.
f A tracheal cannula is easily made by heating a piece of glass tubing,
about 6 inches long, a short distance from one end, and drawing it out slightly
so as to form a ' neck.' The tubing is then bent about its middle to an obtuse
angle, and the end next the neck is ground obliquely on a stone. The diameter
of the cannula should be about the same as that of the trachea, into which it
is to be inserted by its oblique end.
202 THE CIRCULATION OF THE BLOOD AND LYMPH
coil and electrodes for a tetanizing current (Fig. 93, p. 300). With
scissors curved on the flat clip away the hair from the front of the
neck. Put the hair carefully away, and remove all the loose hairs
with a wet sponge so that they may not get into the wounds. Give ether,
or pour into the stomach by a tube 5 c.c. of a 0*5 per cent, solution
of chloroform, in 10 per cent, alcohol per kilo of body-weight, diluted
before administration with 3 or 4 volumes of water (Grehant's method).
To put a Cannula in the Trachea. — The hair having been clipped in
the middle line of the neck and the skin shaved, a mesial incision is
to be made, beginning a little below the cricoid cartilage, which can
be felt with the finger. The trachea is then cleared from its attach-
ments by forceps or a blunt needle, and two strong ligatures are passed
beneath it. A single loop is placed on each of these, but is not drawn
tight. Raising the trachea by means of the upper ligature, the student
makes a longitudinal incision through two or three of the cartilaginous
rings, inserts the cannula, and ties the lower ligature firmly around its
neck. The upper ligature can now be withdrawn.
Clip off the hair on each side of the sternum. Make an incision on
each side through the skin and down to the costal cartilages about
2 inches from the edge of the breast-bone, and long enough to expose
about four costal cartilages (say, 3rd to 6th). With a curved needle
pass waxed ligatures round the cartilages, and tie firmly to compress
the intercostal vessels. The bellows should now, or earlier if any
symptoms of impeded respiration have appeared, be connected with
one end of the horizontal limb of a glass T-piece, the other end of
which is similarly connected with the tracheal cannula. The stem of
the T-piece is provided with a short piece of rubber tubing, which,
when artificial respiration is being carried on, Is to be alternately closed
and opened — closed during inflation of the lungs, and opened when
the air is to be allowed to escape from them. Or a screw-clamp may
be adjusted on the piece of tubing so that the opening is sufficiently
narrow to permit the lungs to be properly inflated when the bellows
are compressed, and yet sufficiently wide to permit easy escape of the
air and collapse of the lungs at the end of each inflation. Ether may,
when necessary, be administered, by inserting between the T-piece and
the tube from the bellows an ether bottle with two tubes passing through
the cork to within an inch or two of the ether. If the cannula has a
side-opening, as is usually the case v/ith metal cannulae, the T-piece
may be dispensed with. One student should take sole charge of the
artificial respiration, which ought to be begun as soon as the chest has
been opened, and continued at the rate of about twenty inflations
per minute. The costal cartilages are rapidly cut through with strong
scissors just on the sternal side of the ligatures, the artificial respira-
tion being suspended for an instant, as each cut is made, to avoid
wounding the lungs. The sternum is divided at its lower end and
turned up. If there is much bleeding a ligature should be tied round
its tipper end. With a curved needle a ligature is passed below the
internal mammary arteries as they approach the sternum. That bone
may now be removed, and the heart, enclosed in the pericardium, comes
into view. A thread is passed with a suture-needle through each side ol
the pericardium, which is then stitched to the chest-wall and opened.
(a) Note the various portions of the heart, right and left ventricles,
right and left auricles, with the auricular app.ndices. Feel the heait
with the hand, and observe that the right ventricle is softer and has
thinner walls than the left, and that the auricles are softer than the
ventricles. Note how all the parts of the heart harden in the hand
during systole and soften during diastole (pp. 86, 90).
PRACTICAL EXERCISES
203
D
(b) Dissect out the vago-sympathetic on one side in the neck of the
dog. The guide to the nerve is the carotid artery. These two struc-
tures and the internal jugu-
lar vein lie side by side in
a common sheath. Feel
for the artery a little ex-
ternal to the trachea, cut
down on it, open the sheath ,
isolate the vago - sympa-
thetic for about an inch,
pass two ligatures under it,
tie them, and divide be-
tween the ligatures. The
peripheral and central ends
of the nerve may now
be successively stimulated.
Stimulation of the peri-
pheral end causes slowing
of the heart, or stoppage
in diastole. Feel that it
softens when it stops. It
soon begins to beat again.
Stimulation of the central
end of the vago-sympa-
thetic may or may not
cause inhibition . If it does,
expose the other vago-
sympathetic, divide it, and
repeat the stimulation of
the central end . There will
now be no inhibition of the
heart. Incidentally it may
be seen that stimulation
of the central end of the
vago - sympathetic causes
strong, though, of course,
withopened chest.abortive,
respiratory movements.
(c) Pith a frog (brain
and cord), dissect out the
sciatic nerve on one side up
to the sacral plexus. Cut
off the whole leg. Drop the
cut end of the nerve on the
heart, and hold the prep-
aration so that the nerve
touches the heart also by
its longitudinal surf ace. At
each cardiac beat the nerve
is stimulated by the action
current (p. 833), and the
muscles of the leg contract.
(d) Raise the board so
that the head of the animal
is down and the hind-feet
up, and note whether there
is any effect on the action
P\U
Fig. 95- — Myocardiograph of Adami and Roy
(modified by Cushny and Matthews). AB, a
perpendicular rod descending from a universal
joint, which is not shown in the figure; CD, a
brass sheath, moving easily on the rod, and
bearing on its upper end an ivory pulley, and at
its lower end a horizontal bar, which is inter-
rupted by a plate of hard rubber, I. The per
pendicular rod EF moves on the horizontal bai
by the hinge-joint, J. EF is hooked at one end
for attachment to the heart, and bored at the
other for a thread which, passing over the pulley
at C, passes through the universal joint and
moves a writing lever not shown in the figure.
CD is prevented from moving up AB by a ring of
brass, G, which is screwed to AB, but is not
attached to CD ; the hook F can therefore move
to and from AB, and can rotate round it, while
it cannot move up or down. The hooks F and B
are insulated from each other by the hard rubber,
I. H is a binding post through which, and
through another connected with A, induction
shocks may be sent at will into the portion
of the heart lying between the hooks.
204
THE CIRCULATION OF THE BLOOD AND LYMPH
and filling of the heart. Repeat the observation with head up and
feet down.
(e) Compress the aorta with the fingers, and observe the effect on
the degice of dilatation of the various cavities of the heart. Repeat
the experiment with the inferior vena cava, and compare the results.
(/) Smoke a drum. Insert the
hooks of the myocardiograph (Fig. 95)
into the ventricle, taking care not
to penetrate deeply into the -wall.
Arrange the lever to write on the
drum. While a tracing is being
taken stimulate the peripheral end of
the vagus. Unhook the cardiograph.
(g) Stop the artificial respiration,
and observe the changes which take
place in the auricles and ventricles,
comparing particularly the right side
of the heart with the left. Before
the heart has stopped beating, re-
commence the artificial respiration.
(h) Connect a cylinder of oxygen
with a good-sized rubber catheter,
'C
Fig. 96. — Arrangement to illustrate Action of Cardiac Valves in the Heart of an Ox
(Gad). C, glass window in left auricle; D, window in aorta; E, tube inserted
through apex of heart into left ventricle and connected with pump P; A, side
tube on E, through which wires are connected with a'tiny incandescent lamp in
the ventricle; W, water in bottle B; T, T', tubes.
and pass the catheter down the trachea! cannula or through a separate
opening in the trachea. Allow a small stream of oxygen to flow into
the lungs. Artificial respiration is now unnecessary. The lungs
remain at rest, yet the blood is sufficiently oxygenated, and the heart
goes on beating. The myocardiographic tracing thus goes on undis-
turbed by respiratory movements.
(i) Stop the oxygen, and resume the artificial respiration. Make a
PRACTICAL EXERCISES
205
Small penetrating wound with a scalpel in the left ventricle. Observe
the course of the haemorrhage, and note especially the difference in
systole and diastole.
(/) Lay the electrodes on the heart, and stimulate it with a strong
interrupted current. The character of the contraction soon becomes
profoundly altered. Shallow, irregular
contractions flicker over the surface, with
a kind of simmering movement sugges-
tive of a boiling pot (delirium cordis,
fibrillar contraction). Now kill the ani-
mal by stopping the artificial respiration.
Observe how l9ng the heart continues to
beat, and which of its divisions stops
last.
(k) Make a dissection of the cervical
sympathetic up to the superior cervical
ganglion, and down through the inferior
cervical ganglion to the stellate or first
thoracic ganglion. Make out the annulus
of Vieussens and the .cardiac sympa-
thetic (accelerator) branches going off
from the annulus or the inferior cervical
ganglion to the cardiac plexus.
14. Perfusion of the Isolated Mam-
malian Heart. — The heart of a dog em-
ployed for some other experiment may
be used. Or a rabbit may be killed by
a blow on the back of the head, and
the heart at once removed. The aorta
should not be cut off too short. Tie a
cannula into the aorta and attach it to
a T-piece connected by rubber tubes,
which must be perfectly clean, with two
bottles, one containing Ringer's solution
(pp. 66, 201), preferably that made with
dextrose, the other containing defibrin-
ated blood diluted with Ringer's solu-
tion. The defibrinated blood should be
strained so as to remove any small pieces
of fibrin. The bottles are supported on a
high stand, so that the level of the bottles
above the heart can be altered, and the
pressure of the perfusion liquid thus
varied. Perfusion may be begun with
Ringer, to wash out any remaining blood
and obviate the possible formation of
clots in the small vessels. Oxygen is
allowed to bubble through the Ringer's
solution, but this is not necessary for the
blood, since, if shaken up, it will retain
far more oxygen than the Ringer's solu-
tion. The temperature of the liquids
should be at about 40° C. when nearing the heart.
,\
: : ~
~:~
- - a
-"-""-
ri~;
- -C
b
1~
- ~~
;,--=-'£
lit
9-
/.
N_
Fig. 97- — Mammalian Heart Per.
fusion Apparatus (Gunn). a,
. Liebig .condenser, cut off as
shown; b, inlet for the warm
water; d, thermometer almost
filling up the lumen of the thin
glass tube c ; e, cork ; /, cannula
for aorta fitted with a collar of
rubber tubing, g, in the end of
the tube c ; h, Y-tube connected
with two reservoirs, one contain-
ing Ringer's solution, the other
any other liquid which is to be
perfused.
can
~ ........... ____ o _________
easily insured by interposing a worm immersed in a heated bath or
other heating arrangement between the cannula and the T-tube, and lor
the study of its movements by inspection the heart itself can be place
in a glass vessel immersed in the bath. tract!
When records of the contract!
2ob
THE CIRCULATION OF THE BLOOD AND LYMPH
are to be obtained, threads are attached to the auricle and to the apex
of the ventricl:. The heart is suspended by fastening the cannula in a
holder on a stand, and the threads, after passing over pulleys to give
them a convenient direction, are attached to writing-levers.
As the heart cannot now be easily kept immersed in the bath, it is
suspended in the air, and can be kept warm by the following simple
arrangement: A copper pipe about 4 inches long is slit on one side, and
on the opposite side is screwed or riveted to a copper rod, under which
is hung a spirit-lamp. The lamp is adjusted at such a point on the rod
that when the copper tube is placed around the heart the heat conducted
along the rod keeps the air around the heart at about body-temperature.
The perfusion liquid before it enters the heart may be heated thus:
A Liebig's condenser is cut through the middle, and the large end
closed by a paraffined cork. A glass tube is run down from the top
through this cork, and the aorta is attached directly to this, so that
the heart is very near the condenser. This tube is mostly filled up by
a thermometer, so that the perfusion liquid passes through it in a thin
stream which is easily heated By the water in the condenser, which
contains a second ther-
mometer. This water is
kept constantly flowing
through the condenser
from a heated bath. The
T-piece connecting with
the perfusion bottles is
attached to the upper
end of the glass tube
to which the heart is
attached (Gunn and
Cushny).
15. Action of the
Valves of the Heart.—
(i) Study the action of
the valves of the ox-
heart, connected with
the pump P and bottle B
in the artificial scheme,
as shown in Fig. 96. The
cavity of the heart is
illuminated by means of
a small electric lamp, the
wires of which pass in at
Fig. 98.— Diagram of Valves of the Heart. The
valves are supposed to be viewed from above, the
auricles having been partially removed. A, aorta
with semilunar valve; B, pulmonary artery and
valve; C, tricuspid, and D, mitral valve; E, right,
andF, left coronary artery ; G, wall of right, and H,
of left auricle, I, wall of right, and J, of left ventricle.
A. When the piston of the pump is pushed down, water is forced
through the aorta D along the tube T into the bottle, and flows back
again into the left auricle by the tube T'. During each stroke of the
pump the auriculo-ventricular valve is seen through the glass disc
inserted into C to close, and the semilunar valve is seen through the
glass in D to open. When the piston is raised, the semilunar valve is
seen to be closed and the auriculo-ventricular valve to be opened.
For comparison, a human heart with a valvular lesion might be used.
(2) With the sheep's or dog's heart provided, perform the following
experiments :
(a) Open the pericardium and notice how it is reflected around the
great vessels at the base of the heart. Distinguish the pulmonary
artery, the aorta, the superior and inferior venae cavae, and the pul-
monary veins. The trachea and portions of the lungs may also be
attached. If so, remove them carefully without injuring the heart.
PRACTICAL EXERCISES 207
(b) Take two wide glass tubes, drawn slightly into a netk at one end.
One of the tubes should be about 10 cm. long, and the other about
50 cm. Tie the short tube A firmly by its neck into the superior vena
cava- the long tube B into the pulmonary artery. Ligature the inferior
vena cava. Connect A by a small piece of rubber tubing with a funnel
supported in a ring on a stand. Pour water into the, funnel till the
right side of the heart is full. It will escape from the left azygos vein,
which must be tied. Put on any additional ligatures that may be
needed to render the heart water-tight. Support B in the vertical
position by a clamp. Fill the funnel with water, and it will rise in B
to the same level as in the funnel. Now compress the right ventricle
with the hand, and the water will rise higher in B. Relax the pressure
and notice that the water remains at the higher level in B, being pre-
vented by the semilunar valves from flowing back into the ventricle.
By alternately compressing the ventricle and allowing it to relax, water
can be pumped into B till it escapes from its upper end, and if this is
so curved that the water falls into the funnel, a ' circulation ' which
imitates that of the blood can be established. Note that during the
pumping the sinuses of Valsalva, behind the semilunar valves at the
origin of the pulmonary artery, become prominent.
(c) Take out B and tear out one of the segments of the semilunar
valve. Replace B, and notice that, while compression of the ventricle
has the same effect as before, the water no longer keeps its level on
relaxation, but regurgitates into the ventricle. This illustrates the
condition known as insufficiency or incompetence of the valves. But
if the injury is not too extensive, it is still possible, by more vigorously
and more rapidly compressing the heart, to pump water into the funnel.
This illustrates the establishment of compensation in cases of valvular
lesion.
(d) Now remove both tubes. Tie the pulmonary artery. Cut away
the greater part of the right auricle. Pour water into the auriculo-
ventricular orifice, and notice that the segments of the tricuspid valve
are floated up so as to close the orifice. Invert the heart, and the
ventricle will remain full of water. Open the right ventricle carefully,
and study the papillary muscles and the chordae tendineai, noting that
the latter are inserted into the lower surface of the -Segments of the
tricuspid valve, as well as into their free edges.
(e) Repeat (b), (c), and (d) on the left side of the heart, tying tube B
into the aorta as far from the heart as possible, and A into the left auricle.
(/) Separate the aorta from the left ventricle, cutting wide of its
origin so as not to injure the semilunar valves, and tie a short wide
tube into its distal end. Fill the tube with water, and notice that the
valves support it. Cut open the aorta just between two adjacent segments
of the valve, and notice the pockets behind the segments, and how they
are related to each other, and connected to the wall of the vessel.
1 6. Sounds of the Heart. — (a) In a fellow-student notice the position
of the cardiac impulse, the chest being well exposed. Use both a
binaural and a single-tube stethoscope. Place the chest-piece of the
stethoscope over the impulse, and make out the two sounds and the
pause, (b) With the hand over the radial or brachial artery, try to
determine whether the beat of the pulse is felt in the period of the
sounds or of the pause. . (c) Listen with the stethoscope over the
junction of the second right costal cartilage with the "sternum, and
compare the relative intensity of the two sounds as heard here with
their relative intensity as heard over the cardiac impulse.
17. Cardiogram. — Smoke a drum, and arrange a recording tambour
and a time-marker beating half or quarter seconds to write on it (Fig. 88,
2o8
THE CIRCULATION OF THE BLOOD AND LYMPH
p. 195). Apply the button of a cardiograph (Fig. 27, p. 90) over your
own cardiac impulse, and fasten it round the body by the bands attached
to the instrument. Connect the cardiograph by an indiarubber tube
with a recording tambour (Fig. 99). Set the drum off at a fast speed,
take a tracing, and varnish it. Compare with Fig. 28 (p. 91), and if
the tracing is sufficiently typical, as is often not the case with human
cardiograms, measure out the time -value of the various events in the
cardiac revolution.
Fig. 99.— Marey's Tambour.
For the cardiograph, a small glass funnel, or thistle-tube, the stem
of which is connected with the recording tambour, may be substituted,
the broad end of the funnel being pressed over the apex-beat.
1 8. Sphygmographic Tracings. — Attach a Marey's sphygmograph
(Fig. 37, p. 103) to the arm. Fasten a smoked paper on the plate D.
Apply the pad C of the sphygmograph to the wrist over the point
where the pulse of the radial
artery can be most distinctly
felt. Ad just the pressure by
moving the screw G. The
writing-point of the lever E
will rise and fall with every
pulse-beat. When everything
is satisfactorily arranged, set
off the clockwork which
Fig. 100. — Dudgeon's Sphygmograph.
moves the plate D, and a pulse tracing will be obtained. Study the
changes which can be produced in the pulse curve — (a) by altering the
position of the body (sitting, standing, and lying down); (6) by exercise
(Fig. loi) ; (c) by inhalation of 2 drops of amyl nitrite poured on a hand-
kerchief by the demonstrator (Fig. 102); (d) by raising the arm above
the head and letting it hang at the side ; (e) by compression of the brachial
artery at the bend of the elbow; (/) by altering the pressure of the pad
Varnish the tracings after marking on them the conditions under which
they were obtained.
A Dudgeon's sphygmograph (Fig. 100) may also be employed. In
this the clockwork carries the strip of blackened paper aloirg beneath
PRACTICAL EXERCISES
209
Fig. 101. — Effect of Exercise on the
Pulse (Marey). Upper tracing,
normal ; lower, after running.
the needle which records the movements of the artery. Or a small
glass funnel or thistle-tube connected with a recording tambour may
be pressed over the carotid artery. The lever of the tambour writes
on a drum, on which at the same time half or quarter seconds are
marked by an electro-magnetic signal.
19. Venous Pulse Tracing from the
Jugular Vein. — Arrange a recording
tambour to write on a drum. Con-
nect the tambour with the stem of a
small glass thistle-tube or funnel (or
with a small metal cup) by a piece of
narrow rubber tubing, and apply the
cup-shaped end of the thistle-tube
over the right jugular bulb of a
fellow-student. This lies about i inch
external to the right sterno-clavicular
articulation, and a little above it. The
receiver may have to be moved about
a little until the best pulsation is
obtained. The ' patient ' should be
lying down, the shoulders slightly raised, the head on a pillow and turned
slightly to the right, in order to relax the right sterno-mastoid muscle
(Mackenzie).
20. Polygraph Tracings.— Arrange the polygraph over the radial
artery, as with an ordinary sphygmograph, so that the lever will record
the radial pulse when the strip of paper is set moving. If the instru-
ment has only one tambour, con-
nect the tambour to a receiver
or thistle-tube over the jugular
bulb. The writing-point of the
tambour is arranged so as to be
immediately below the writing-
point connected with the radial.
If the polygraph is provided
with clockwork to record time,
set off the time -marker writing
fifths of a second. When it is
seen that the writing-points are
marking properly, start the
clockwork which moves the
strip of smoked paper. Repeat
the observation with the tam-
bour connected with the apex-
beat. Letter the curves as far
Fig. 102.— Effect of Amyl Nitrite on the as possible as in Figs. 65 and
Pulse (Marey). Upper tracing, normal; 66 (p. 149) without at present
lower, after inhalation of amyl nitrite. attempting their exact analysis.
If the polygraph has two tam-
bours, simultaneous tracing of the radial pulse, the jugular pulse, and the
cardiac impulse, or of the carotid pulse, the jugular pulse, and the apex-
beat, may be taken, and other combinations as well. If no polygraph
is available, a drum may be employed, the tracings being all taken with
thistle-tubes connected with recording tambours. The levers of the
tambours must be arranged to write on the drurh in the same vertical
straight line, or, without making the adjustment quite exact, vertical lines
of reference may be drawn through each curve, with the drum at rest,
indicating the relative positions of the writing-points.
2io THE CIRCULATION OF THE BLOOD AND LYMPH
21. Plethysmographic Tracings. — Connect the vessel D (Fig. 36,
p. 128), directly with a recording tambour by the tube F, omitting for
simplicity the recording arrangement in the figure. Place the arm
in the plethysmograph, and adjust the indiarubber band to make
a watertight connection. Support D so that the arm rests easily
within it, and fill it with water at body temperature. No water must get
into the tambour, and it is well to insert a piece of glass tubing in the
connection between it and the plethysmograph, so that it may be seen
when the water is rising too high. A T -piece with a short piece of
rubber tubing on the stem should be inserted in the course of the tube
leading to the tambour. All adjustments are made with the T-piece
open, and when a tracing is to be taken the short rubber tube is closed
by a clip. Arrange a time-marker to write half or quarter seconds
(Fig. 88, p. 195). Adjust the writing-point to write on a drum, and
close the upper tubulure C with a cork. The quantity of blood in the
arm is increased with every systole of the left ventricle, diminished in
diastole. The lever will therefore rise when the ventricle contracts,
and sink when it relaxes.
(1) Take tracings with the arm (a) horizontal, (b) hanging down.
(2) With the arm horizontal, take tracings to show the effect (a) of
closing and opening the fist Inside the plethysmograph;* (b) of apply-
ing a tight bandage round the arm a little way above the indiarubber
band ; (c) of inhaling 2 drops of amyl nitrite.
Instead of the arm plethysmograph, a small plethysmograph to hold
a finger may be employed. It consists of a glass tube drawn out at
one end. The wide end is provided with a rubber collar. The narrow
end is connected by a small rubber tube with a very small and sensitive
recording tambour, a T-piece being inserted on the connection as before.
With the T-piece closed fill the tube with water. Then, holding up the
wide end of the tube, the tip of the finger is put in so as just to close
the tube. The T-piece is then raised and opened, and the finger pushed
in as far as it will go. The collar must fit the finger so as to form a
watertight joint. Now get the proper pressure in the tambour by
blowing into the T-piece, and close the clamp. A time-tracing can be
taken as before.
22. Pulse-Rate. — (i) Count the radial pulse for a minute in the
sitting, supine, and standing positions. Use a stop-watch, setting it
off on a pulse-beat and counting the next beat as one. Make three
observations in each position.
(2) Count the pulse in a person sitting at rest, and then again in the
sitting position immediately after active muscular exertion. Note how
long it takes before the pulse-rate comes back to normal.
(3) Count the pulse in a person sitting at rest. Repeat the observa-
tion while water is being slowly sipped, and note any change.
(4) With one hand over the thorax of a rabbit, count its pulse. Then
notice the effect (a) of suddenly closing its nostrils, (b) of bringing a
small piece of cotton-wool sprinkled with ammonia or chloroform in
front of the nose (reflex inhibition of the heart}.
23. Blood-Pressure Tracing. — (a) Put a dog under morphine (p. 63).
Set up an induction machine arranged for an interrupted current
(Fig. 93, p. 200). Fill the U-shaped manometer tube (if this has
not already been done) with clean mercury to the height of 10 to
12 cm. in each limb. If the float tends to stick, half an inch of oil
may be put above the mercury in the distal (straight) limb before
putting in the float. But where the mercury is clean and dry, and the
* Closing the fist causes a fall in the curve — i.e., a diminution in the volume
of the arm. On opening the hand, the curve regains its level.
PRACTICAL EXERCISES 211
size of the float properly adjusted to that of the tube, this is not neces-
sary, and is to be avoided. Then, tilting the tube carefully, fill the
proximal limb (i.e., the limb which is to be connected with the blood-
vessel) with a saturated solution of sodium carbonate or a half -saturated
solution of magnesium sulphate, or, what is better for most purposes,
a 2 per cent, solution of sodium citrate. This is easily done by means
of a pipette furnished with a long point. Now attach a strong rubber
tube to the proximal end of the manometer, and fill it also with the
solution. All air must be got out of the manometer and its connecting-
tube. Raise the end of the rubber tube and blow into it, so as to cause
a difference of about 10 cm. in the height of the mercury in the two
limbs of the manometer, and, without releasing the pressure, clamp the
tube with a pinchcock or screw clamp (Fig. 4 - , p. no).
Now smoke a drum, and arrange the writing-point of the manometer-
float so that it will write on it. Suspend a small weight by a piece of
silk thread from a support attached to the stand of the drum, so that
it hangs down outside of the writing-point of the manometer-float and
always keeps it in contact with the smoked surface without undue
friction. Or a piece of glass rod drawn out to a fine thread in the
blowpipe flame answers very well. Below the writing-point of the
float, and in the same vertical line with it, adjust the writing-point
of a time-marker beating seconds (Fig. 88, p. 195).
Next fasten the animal on a holder, back down. Give ether and
insert a tracheal cannula (p. 202). (The tracheal cannula is not abso-
lutely required for the experiment, but it is convenient, as the animal
is more under control, and artificial respiration can be begun at any
moment, should this be necessary.) Insert a glass cannula, armed
with a short piece of rubber tubing, into the central (cardiac) end of
the carotid artery (p. 63). Leaving the bulldog forceps on the artery,
fill the cannula and tube with the sodium citrate or one of the other
solutions. Slip the rubber tube over a short glass connecting-tube. Fill
this also with the solution, and connect it with the manometer-tube,
seeing that both are quite full of liquid, so that no air may be enclosed.
Where a permanent working place is provided for blood-pressure
experiments it is convenient to connect the cannula and manometer
with a pressure -bottle containing the sodium citrate solution, and to
use a three-way cannula for the bloodvessels (Fig. 103). The cannula
has a bulbous enlargement, which hinders clotting. The end of the
cannula is connected with the tube from the pressure -bottle, which is
closed by a clip, and the side-tube is connected with one limb, E, of
the manometer shown in Fig. 104. E is itself provided with a side-
tube, F, armed with a short piece of rubber tubing. The cannula does
not require to be filled with liquid before being inserted into the artery.
By opening F and releasing the clip on the tube from the pressure-
bottle the cannula and the tube connecting it with the manometer can
be filled, and any blood-clots can be easily washed out in the course of
an experiment. Before the bulldog forceps is taken off the artery to
obtain a blood-pressure tracing, F must be closed, and the clip on the
tube from the pressure-bottle opened. The bottle is attached to a
strong cord passing over a pulley, by which it is raised to a height
sufficient to balance approximately the pressure in the artery. The
tube to the pressure-bottle is then clipped. If no manometer with
side-tube is available, a T-piece can be inserted in the connection
between the cannula and the manometer, and the cannula can be
washed out through this.
Now take the bulldog forceps off the artery, and allow the drum to
revolve at slow speed. The writing-point of the manometer-float will
212
THE CIRCULATION OF THE BLOOD AXD LYMPH
trace a curve showing an elevation for each heart-beat, and longer
waves due to the movements of respiration.
(6) Isolate the vago-sympathetic nerve
in the neck. Ligature doubly, and cut
between the ligatures. Stimulate the peri-
pheral (lower) end ; the heart will be slowed
or stopped, and the blood-pressure will fall. -.
Stimulate the central (upper) end; there B
may be inhibition of the heart or accelera-
tion, and the pressure may fall or rise
(p. 170).
(c) Expose and divide the other vago-
sympathetic while a tracing is being taken.
4gain stimulate the central end of the
nerve and observe whether there is any
effect.
(d) Expose the sciatic nerve in one leg,
as follows: The leg having been loosened
from the holder, the foot is seized by one
hand and lifted straight up, so as to put
Fig. 103. — Three-way Cannula.
the skin of the thigh on the stretch. An
incision is now made in the middle line on
the posterior aspect of the thigh, through
the skin and subcutaneous tissue. The
muscles are separated in the line of the
incision with the fingers, and the sciatic
nerve comes into view lying deeply be-
tween them. Place a double ligature on it,
and divide between the ligatures. Stimu-
late the upper (central end) ; the blood-
pressure probably rises, and the heart may
be accelerated. Stimulate the peripheral
end of the nerve ; there is little change in
the blood-pressure and" none in the rate of
the heart.
(e) Note, incidentally, that stimulation
of the central end of the sciatic or the upper
(cephalic) end of the vago-sympathetic
may cause increase in the rate and depth of the respiratory movements.
Dilatation of the pupil is also caused by stimulation of the upper end of
Fig. 104. — Manometer with
Side-tube (Guthrie). A, float ;
B, collar through which the
wire C of the float moves; D.
vertical wire fixed to mano-
meter-holder, which keeps the
writing-point on the drum;
E, limb of manometer con-
nected with cannula, with its
side-piece, F.'
ZI3
the vago-sympathetic through the sympathetic (pupillo-dilator) fibres
that supply the iris.
(/) Again stimulate the peripheral end of one vagus, or of both at
the same time, while a tracing is being taken, and see how long it is
possible to keep the heart from beating. Sometimes, but rarely in the
dog, inhibition can be kept up so long that the animal dies.
(g) Close the tracheal cannula so that air can no longer enter the
lungs. In a very short time the blood-pressure curve begins to rise
(rise of asphyxia). After some minutes the pressure falls, and finally,
when the circulation has stopped completely and the pressure has
become equalized throughout the whole vascular system, a residual
pressure of only a few mm. (usually about 10 mm. Hg) is indicated.
In order to^get the true zero pressure, disconnect the arterial cannula
S { i m ul oi i on of
centrol end .stopped
Peripheral end
.fet A rn u 1 air e cl
c e n t r c* 1
ti inulated-
Fig. 105. — Blood- Pressure Tracing from a Dog: Stimulation of Central and Peripheral
Ends of Vagus. The other vagus was intact. Stimulation of the peripheral end
caused stoppage of the heart and a marked fall of pressure. Stimulation of the
central end produced a great rise of pressure, with, perhaps, a slight acceleration
of the heart.
from the manometer, and allow the writing-point to trace a horizontal
straight line (line of zero pressure) on the drum (Figs. 84 and 85).
24. Estimation of the Arterial Blood-Pressure in Man. — Use the Riva-
Rocci apparatus, as described on p. 113. Begin with the subject in the
sitting position. The observer's left hand may be used for palpating
the pulse, and the right for working the bulb. Employ the ausculta-
tory method as well as palpation, and determine the systolic and dias-
tolic pressures. Repeat the observations with the person standing up
and lying down. Investigate the effect of muscular exercise on the
blood-pressure.
25. The Influence of the Position of the Body on the Blood-Pressure.
— Inject into the rectum of a dog 3 to 4. gnu. of chloral hydrate dis-
solved in a little water. See chat it does not run out again immediately
214 THE CIRCULATION OF THE BLOOD AND LYMPH
after injection. In ten minutes anaesthetize the animal fully with a
mixture of equal parts of alcohol, chloroform, and ether (one of the
so-called A.C.E. mixtures), or with chloroform, and tie it very securely,
back downward, on a board, which can be rotated around ajiorizontal
axis, corresponding in position to the point at which the cannula is to
be inserted.* Set up a drum and manometer as in 23 (p. 210), but with
a rubber connecting-tube of such length as will allow free rotation of
the board. Put a cannula in the trachea. Insert a cannula into the
central end of the carotid artery at a point immediately above the axis
of rotation of the board, and connect it with the manometer.
(a) Take a blood-pressure tracing with the board horizontal.
(6) Whilst the tracing is being taken, rotate the board so that the
position of the animal becomes vertical, with the feet down. Mark
on the tracing the moment when the change of position takes place.
The pressure falls. Replace the dog in the horizontal position. The
manometer regains its former level. Now rotate the board, till the
animal is again vertical, but with feet up and head down, and observe
the effect on the blood-pressure. The respiratory variations in the
pressure are usually greater with feet down than with head down.
Notice in both cases whether there is any change in the rate of the heart.
(c) Take the board off the stands, lay it on a table, expose the femoral
artery, and insert a cannula into it. Shift the axis so that it now lies
below this cannula. Replace the board on the stands, and repeat (a)
and (6). The fall of pressure will now take place in the head-down
position. f In the feet-down position (with the cannula in the femoral
artery) a rise of pressure in general takes place. But sometimes this
is very small, and lasts only a few seconds, being succeeded by a fall,
during which the heart-beats on the tracing are much weaker than
before, since enough blood is not reaching the heart to enable it to
maintain the pressure. In the feet-down position see whether the
corneal reflex can be got. If not, as is likely, turn the animal into the
head-down position. The reflex may now soon be obtained, and it
may again disappear on putting the animal in the feet-down position.
If the chloroform anaesthesia is light the reflex may not be abolished
in the feet-down position, although strong respiratory movements may
occur, owing to anaemia of the medulla oblongata.
26. Effects of Haemorrhage and Transfusion on the Blood-Pressure.
— Anaesthetize a dog with morphine and ether, and insert a cannula
into the trachea. Put a cannula into 'the central end of the carotid
artery and another into the central end of the femoral artery. Then
insert a cannula, which should have a piece of indiarubber tubing 2 to
3 inches in length on its wide end, into the central end of the femoral
vein on the opposite side. In doing this more care is necessary than
* A simple arrangement for this purpose is a board with a number of staples
fastened in pairs into its lower surface, so that an iron rod can be pushed
through any pair, and form a horizontal axis at right angles to the length of
the board. The dog having been tied down, the rod is pushed through the
pair of staples corresponding to the position of the cannula in the artery that
is to be connected with the manometer. The projecting ends of the rod rest
in two ordinary clamp-holders, fastened at a convenient height on two strong
stands, whose bases are clamped to the end of a table. The other end of the
board is supported by a piece of wood that rests on the floor, and can be re-
moved when the board is to be rotated.
f In 1 6 dogs the fall of pressure in the carotid in the feet-down position
varied from 12 to 100 mm. of mercury; average fall, 44-4 mm. In 12 out of
the 16 animals the rise of pressure in the head-down position varied from
2 to 36 mm. ; in i there was no change; in 3 there was a fall of 5 to 24 mm.
PRACTICAL EXERCISES 215
in putting a cannula into an artery. Feel for the femoral artery, cut
down over it, and with forceps or a blunt needle separate the femoral
vein from it for about an inch. Pass two ligatures under the vein, and
tie a loose loop on each. Put a pair of bulldog forceps on the vein
between the ligatures and the heart. Now tie the lower (distal) liga-
ture, and cut one end short. The piece of vein between it and the
bulldog forceps is thus distended with blood, and this facilitates the
next step. With fine-pointed scissors make a snip in the wall of the
vein. The cannula is now pushed through the slit in the vein, and
the upper ligature tied firmly round its neck. By the aid of a pipette,
made by drawing a piece of glass tubing out to a long point, the canmila
and rubber tube are then completely filled' with o'g per cent, salt
solution. Be sure to pass the point of the pipette right down to the
point of the cannula, so as to dislodge any bubble ol air that may tend
to cling there. Then, holding up the open end of the rubber tube,
close it, without allowing any air to enter, by means of a screw clamp
or bulldog forceps, or a small piece of glass rod. Connect the cannula
in the carotid with a manometer, arranged to write on a drum as in
experiment 23 (p. 210). Take the bulldog off the carotid, and measure
the difference in the level of the mercury in the two limbs of the man-
ometer with a millimetre scale.
(1) (a) While a tracing is being taken, draw off about 10 c.c. of blood
from the femoral artery, and observe whether there is any effect on
the tracing. Mark on the tracing the moment when the removal of
the blood begins and ends.
(b) Repeat (a), but run off about too c.c.* of blood, and let this be
immediately defibrinated. Then draw off portions of 100 c.c.* at short
intervals until a distinct fall of blood-pressure has been produced. All
the samples of blood should be denbrinated and strained through
cheese-cloth.
(2) (a) Now, while a tracing is being taken, inject the whole of the
denbrinated blood slowly through the cannula in the femoral vein by
means of a funnel supported by a stand at such a height that the blood
runs in easily. A pinchcock should be put on the tube connecting the
funnel and the cannula, and this should be closed before the funnel is
quite empty, so as to obviate any risk of air getting into the vein. Of
course, the cannula and connecting-tubes must all be freed from air
before injection is begun. Again measure the difference in the level
of the mercury and compare the pressure with that observed before
the first haemorrhage.
(b) Inject into the vein, while a tracing is being obtained, about
100 c.c.* of o'9 per cent, salt solution heated to 40° C., and go on
injecting portions of 100 c.c. until a distinct rise of pressure has taken
place, keeping a record of the total amount injected, and marking the
time of each injection on the curve.
(c) After an interval of thirty minutes, again measure the height of
the mercury in the manometer. Then bleed the dog to death while a
tracing is being recorded.
27. The Influence of Proteoses (and Peptones) on the Blood-Pressure.
— Set up the apparatus for taking a blood-pressure tracing as in experi-
ment 23 (p. 2 TO), but omit the induction-coil. Weigh a dog. Weigh
out a quantity of Witte's peptone equivalent to 0*5 grm. for every kilo
of body-weight. Dissolve the peptone in about ten time's its weight
of o'Q per cent, salt solution. Anaesthetize the dog with morphine and
ether or A.C.E. mixture. Insert a cannula into the trachea. Put
cannulae into the central end of one carotid and of one femoral vein
* 200 c.c. for a large dog.
216 THE CIRCULATION OF THE BLOOD AND LYMPH
(p. 214). Connect the carotid with the manometer, and the femoral
vein with a burette or large syringe containing the peptone solution.
Take care that the connecting-tube and cannula are free from air.
Now commence to take a blood-pressure tracing, and while it is going
on inject the peptone solution. The pressure falls owing largely to
a dilatation of the small arteries through the direct action of the pep-
tone on the ir muscular tissue or on the endings of the vaso-motor nerves.*
28. Effect of Suprarenal Extract on the Blood-Pressure. — Make the
arrangements for a blood-pressure tracing from a dog as in 23 (p. 210).
Put a cannula in the carotid and another in the femoral vein or one of
its branches (p. 214). Expose both vagi in the neck, and pass threads
loosely under them. Connect the carotid with the manometer and
take a tracing. Then, while the tracing is continued, inject slowly
into the femoral vein an amount of watery extract corresponding to
about 0*2 grm. of suprarenal, or, what is more convenient, a few c.c.
of a solution of adrenalin chloride of the strength of i to 50,000 in
0*9 per cent/ sodium' chloride solution, the dose depending, of course,
on the size of the animal. The blood-pressure risesf owing to con-
Fig. 106. — Effect of Injection of Peptone on the Blood-Pressure in a Dog.
(To be read from right to left.)
striction of the arterioles by direct excitation of the junction between
their vaso-constrictor nerves and their muscular tissue. The heart is
slowed, but its beat is strengthened. At once cut both vagi while a
tracing is being taken; the blood-pressure rises still more (p. 655).
The rise of pressure is sometimes so great that to prevent the mercury
from being forced out of the manometer the tube must be clipped.
The rise is not long maintained, but a second injection causes a renewed
increase of pressure.
29. Action of Epinephrin (Adrenalin) on Artery Rings. — The experi-
ment (8) described on p. 66 in connection with the constrictor action
of serum may equally well be performed here.
* In 12 dogs the blood-pressure always fell, the amount of the fall varying
from 81 to 21 mm. of mercury (average, 60 mm.). It sometimes returned to
normal in twenty to thirty minutes, but usually required a longer time. In
some dogs, after the injection of the whole of this amount of peptone, death
occurs before there has been any considerable recovery of the pressure.
f The amount of the initial rise of pressure is very variable, since the slow-
ing of the heart tends to diminish the pressure, while the constriction of the
arterioles tends to increase it. Thus, in one experiment the increase of pres-
sure on injection of the extract was only 6 mm. of mercury, while in another
it was 56 mm. On section of the vagi in this second experiment, there was
an additional rise of 64 mm., and after a second injection a further rise of
70 mm., making an increase of 190 mm. in all above the original pressure.
PRACTICAL EXERCISES
2J7
30. Determination of the Circulation-Time. — (a) Begin with ail arti-
ficial scheme (Fig. 107). Fill the syringe with a 0-2 per cent, solution
of methylene blue. Allow the water to flow from the bottle by loosen-
ing the clamp. Inject a definite quantity of the methylene-blue solu-
tion, and with a stop-watch observe how long it takes to pass from
the point of injection to the end of the glass tube filled with beads
Make ten readings of this kind, and take the mean. Then raise the
bottle so as to increase the ra' e of flow of the water, and repeat the
observations. The ' circulation- time ' will be found to be diminished.
^a This corresponds to an increase of
, .F\^ : blood- pressure due to increased act
tivity of the heart, without change
in the calibre of the bloodvessels.
Next, leaving the bottle in its present
position, diminish the outflow by
tightening Ihe clamp; the circulation-
time will be increased. This corres-
ponds to an increase of blood-pressure
due to diminution in the calibre of
the small arteries.
(b) Fill the syringe* with methy-
lene-blue solution (0-2 per cent, in
Fig. 107. — Artificial Scheme to illustrate a Method of measuring the Circulation-
Time. B, bottle containing water, the rate of outflow of which is regulated by
screw-clamp a; S, syringe filled with methylene-blue solution, connected with
T-piece A; M, beaker containing methylene-blue solution; b, c, screw-clamps;
C, T-piece, inserted in the course of the flexible tube E, and connected with the
glass tube T, which is filled with beads; F, outflow tube. The clamp c having
been closed and b opened, the syringe is filled with the methylene-blue solution;
b is then closed, c opened, and a definite quantity of the solution injected into the
system. The time from the beginning of injection till the appearance of the blue
at G is measured with the stop-watch.
0-9 per cent, salt solution), as in (a). Keep the solution warmed to
40° C. by immersing the small beaker containing it in a water-bath, or
heating it over a Bunsen with a small flame. Weigh a rabbit or cat.
In the case of the rabbit, inject 1 grm. chloral hydrate into the rectum,
and later on give ether if necessary. If a cat, give ether alone, or
urethane (1-5 grm. per kilo by stomach tube i to 2 hours before).
Fasten it on a holder, back downwards (Fig. 61, p. 136). Cover it with
a towel to keep it warm. Clip off the hair on the front of the neck, and
make an incision i J inches long in the middle line, beginning a little
* A burette, sloped so as to make a small angle with the horizontal, may
be substituted for the syringe. The burette is supported on a stand at such
a height (say 10-15 cm. above the level of the caiinula) that the methylene-
blue solution runs without great force into the jugular. The danger of pro-
ducing an abnormal result by suddenly raising the pressure in the right side
of the heart is thus avoided.
2i8 THE CIRCULATION OF THE BLOOD AND LYMPH
way below the cricoid cartilage. Reflect the skin and isolate the
external jugular vein, which is quite superficial. Carefully separate
about £ inch of the vein from the surrounding tissue, and pass two
ligatures under it. but do not tie them. Compress the vein with a pair
of bulldog forceps between the heart and the ligatures. Now tie the
uppermost of the two ligatures (that next the head), but only put a
single loose loop on the other. The piece of vein between the upper
ligature and the bulldog is now distended with blood. With fine-
pointed scissors make a small slit in the vein, taking great care not to
divide it completely, insert the cannula, and tie the loose ligature firmly
over its neck. Fill the cannula and the small piece of rubber tubing
attached to it with 0*9 per cent, salt solution by means of a pipette
with a long point. Expose the carotid on the other side, isolate it lor
f inch, clear it carefully from its sheath, slip under it a strip of thin
sheet indiarubber, and between this and the artery a little piece of white
glazed paper. Connect the cannula in the jugular with the T-piece
attached to the syringe. Care must be taken that no air remains in
the cannula or its connecting-tube, as a rabbit not unfrequently dies
instantaneously when a bubble of air is injected into the right heart,
although a considerable quantity of air can generally be injected into
the jugular of a dog without killing it.
Now take off the bulldog from the vein, and make a series of observa-
tions on the pulmonary circulation-time. The animal must be so
placed that a good light falls on the carotid. If necessary, the light
of a gas-flame may be concentrated on it by a lens. The student holds
the stop-watch in one hand, and injects a measured quantity of the
methylene-blue solution with the other. Uniformity in the quantity
injected is secured by fastening on the piston of the syringe a screw-
clamp, which stops the piston at the desired point. The observation
consists in setting off the watch at the moment when injection begins
and stopping it when the blue appears in the carotid. After each
injection the screw-clamp or pinchcock on the tube connected with the
cannula must be tightened, the other opened, and the syringe refilled.
Great care must be taken never to open the two clamps at the same
time, as in that case blood may regurgitate through the jugular and
fill the syringe, or methylene blue may be sucked into the circulation.
As many observations as possible should be taken, and the mean
determined. The circulation -time observed is approximately that of
the lesser circulation, the time taken by the blood to pass from the
left ventricle to the carotid being negligible for the purposes of the
student.
The specific gravity of the blood may also be tested at the beginning
and end of the experiment by Hammerschlag's method (p. 62). If
a large number of injections have been made in quick succession, the
specific gravity will be less than normal; but if a considerable interval
has been allowed to elapse after the last injection, little or no differ-
ence may be found, as the surplus liquid readily passes out of the
bloodvessels.
Necropsy. — Observe particularly the state of the lungs, whether the
bladder is distended or not, and whether any of the serous cavities or
the intestines contain much liquid; so as to determine, if possible, by
what channel the water injected into the blood may have been elimin-
ated. Study the distribution of the methylene blue in such organs as
the kidneys and the muscles immediately after death, and notice that
the blue colour becomes more pronounced after exposure for a time to
the air. Make a longitudinal section through a kidney, and observe
that the pigment is found especially in the cortex and around the
PRACTICAL EXERCISES 219
pelvis at the apices of the pyramids, or it may be only in the cortex.
The urine is greenish. If some methylene blud has been injected after
the heart ceased to beat, the bloodvessels, particularly in the mesentery,
may be beautifully mapped out by the pigment. This is not the
case if the last injection took place before death, since the methylene
blue is rapidly reduced by living tissues to a colourless substance,
leuco-methylene blue.
31. Measurement of the Blood-Flow in the Hands. — Arrange the
calorimeters as in Fig. 108. The thermometers in the calorimeters
should be graduated in tenths of a degree, so that by means of the small
lenses or ' readers ' which slide on the stems hundredths of a degree
can be estimated. Where it is desirable that a number of students
should make observations in as short a time as possible, one calorimeter
can be allotted to each subject, the other hand being kept in the pocket
or covered with a glove if the room is cool, so as to avoid reflex vaso-
motor interference. A felt collar is chosen which fits the wrist closely.
A horizontal pencil-mark is made at the lower edge of the styloid
process of the ulna, and another parallel mark at a distance above this
slightly greater than the thickness of the collar. When this second
mark is just kept in view above the collar with the hand in the
calorimeter, the first (lower) mark will be jiut below the level of the
lid. A large bath holding 20 or 30 litres or niore (a clean ' garbage '
or ' offal ' can is suitable) is filled with water at about 32° C. The
exact temperature is not important, but it should be about the same
in all measurements which are to be compared. An ordinary ther-
mometer graduated in degrees is all that is necessary for reading the
temperature of the bath. The calorimeters are now filled from the
bath. They are conveniently made of such a size that 3 litres of water
and the hand can be contained in them without any slopping over
when the water is stirred. Time is saved by having a metal flask
which just holds the quantity of water that goes into each calorimeter.
The orifices of the calorimeters are closed by felt discs. The subject,
sitting in a high chair placed between the calorimeters, now immerses
his hands in the bath to a point between the two marks. The fingers
are kept spread. The bath is occasionally stirred. An ordinary ther-
mometer suspended at the back of the chair gives the room tempera-
ture. After ten minutes the hands are withdrawn from the bath, the
wrists rapidly dried with a towel, the hands at once introduced into the
calorimeters, and the felt collars adjusted round the wrists. The sub-
ject leans back comfortably in the chair, allowing the arms to hang
down without effort. The fingers are kept slightly spread. The ob-
server sits on a low seat behind the subject, and reads the thermometers
from time to time, always after stirring the water well with goose-
feathers passing through the stirring-holes in the lid. The readings
can be made at intervals of a minute, two minutes, or any interval
which is convenient. At the end the hands are quickly withdrawn,
the felt discs put over the orifices, and the water vigorously. stirred for
ten or fifteen seconds before the thermometers are read. In this way
any errors due to imperfect stirring or to accidental contact of the
hands with the thermometers are eliminated.
The volume of each hand is now measured by immersing it exactly
to the lower mark in water contained in a glass douche-can connected
by a short rubber tube with a pipette furnished with a side-tube at its
lower end. The lowest graduation on the burette (50 on a 50 c.c.
burette) is brought level with the water before the hand is immersed,
While the hand is being held steadily and vertically in the water by
an assistant, the level of the water in the burette is read off. All that
220 THE CIRCULATION OF THE BLOOD AND LYMPH
is necessary to get the volume of the hand is to pour water into the
can from a graduated measure after withdrawal of the hand until the
same level is reached. Or the value of a division of the burette can
be determined once for all. The burette is simply used as a transparent
scale. When the two hands are successively measured, the small
amount of water removed by the first is automatically restored by
dipping the second into a separate vessel of water, and putting it wet
into the douche-can. The rectal t mperature should now be obtained.
The temperature of the arterial blood entering the hand is taken as
0-5° C. below that of the rectum. If only the mouth temperature can
be got, the thermometer should be put in a second time without shaking
Fig. 108. — Calorimetric Method of measuring Blood-Flow in Hands.
down to see if it rises any more. The mouth temperature is taken as
equal to the arterial blood temperature.
After thorough stirring, the calorimeter temperatures can now be
read again. The two being noted, the amount of cooling of the calor-
imeters can be determined. This has to be added to the actually
observed rise of the thermometers during immersion of the hands.
Suppose an experiment yielded the following data: Rise of ther-
mometer in a calorimeter in twenty minutes during immersion of a hand
in it, ro° C. ; temperature of calorimeter at beginning of the twenty
minutes, 3i'o° C. ; at end of twenty minutes, 32-0° C. ; cooling of calor-
imeter in twenty minutes, o'l8 C. ; water in calorimeter, 3,000 c.c.;
PRACTICAL EXERCISES 221
volume of hand, 450 c.c.; rectal temperature, 37'o° C.; water equivalent
of calorimeter, 100 c.c.
The water equivalent of the hand is 450 x o-8*= 360 c.c.
The water equivalent of the calorimeter is - 100 c.c.
Water - - 3,000 c.c.
Total - - 3,460 c.c.
3,46ox n = 3,8o6 small calories given off by the hand in twenty
minutes.
Temperature of arterial blood (36' 5°) minus temperature of venous
blood (31*5*, the mean temperature of the calorimeter) = 5*0.
3,806 lot
Flow per minute through hand=- x — ' =42*3 grm.
20 x 5 9
Flow per 100 c.c. of hand per minute = 9' 4 grm.
The readings of the calorimeter thermometers for the first one or two
minutes may not be usable, owing to disturbance caused by the intro-
duction of the hands. As soon as they begin to rise steadily and
uniformly, the readings can be utilized for the calculation of the flow.
32. Vasomotor Reflexes. — Begin as in 31,, Then, after the hands
have been in the calorimeters for a sufficient period (say ten minutes) to
allow satisfactory readings for the determination of the blood-flow to
be obtained, rapidly transfer one hand to cold water (at about 8° C.),
while the other remains in the calorimeter. Continue reading the
calorimeter thermometer. Its rise will be checked by reflex vaso-
constriction. If the hand is kept for a few minutes in the calorimeter,
the reflex vaso-constriction of the hand in the calorimeter will probably
disappear, and the thermometer will rise faster. When a sufficient
number of readings have been obtained for calculating the alteration
in the flow, which will usually be the case in eight or ten minutes,
transfer the hand from the cold water to warm water (at about 43° C.),
and continue reading the calorimeter thermometer. There is usually
a reflex vaso-constriction followed by vaso-dilatation.
* This factor is the product of the specific gravity and the specific heat of
the hand. The volume multiplied by the specific gravity gives the mass of
the hand, which multiplied by the specific heat, gives the water equivalent of
the hand.
t The reciprocal of the specific heat of blood (see formula, p. 122).
CHAPTER IV
RESPIRATION
RESPIRATION in its widest sense is the sum total of the processes by
which the ultimate elements of the body gain the oxygen they
require, and get rid of the carbon dioxide they produce.
SECTION I. — PRELIMINARY ANATOMICAL DATA.
Comparative. — In a unicellular organism no special mechanism of
respiration is needed; the oxygen diffuses in, and the carbon dioxide
diffuses out, through the general surface. The simple wants of such
multicellular animals as the coelente rates, the group to which the sea-
anemone belongs, are also supplied by diffusion through the ectoderm
from and into the surrounding water, and through the endoderm from
and into the contents of the body-cavity and its ramifications.
But in animals of more complex structure special arrangements
become necessary, and respiration is divided into two stages: (i) Ex-
ternal respiration, an interchange between the air or water and a cir-
culating medium or blood as it passes through richly vascular skin,
gills, trachea?, or lungs; and (2) internal respiration, an interchange
between the blood, or lymph, and the cells.
In the lower kinds of worms respiration goes on solely through the
skin, under which plexuses of bloodvessels often exist, but in some
higher worms there are special vascular appendages that play the part
of gills. The Crustacea also possess gills, while in the other arthropoda
respiration is carried on either by the general surface of the body (in
some low forms), or more commonly by means of trachea, or branched
tubes .surrounded by blood spaces and communicating externally with
the air and internally by their finest twigs with the individual cells.
Most of the mollusca breathe by gills, but a few only by the skin.
Among vertebrates the fishes and larval amphibians breathe by gills,
but most adult amphibians have lungs. The skin, too, in such animals
as the frog has a very important respiratory function, more of the
gaseous exchange taking place through it in some conditions than
through the lungs.
One small group of fishes, the dipnoi, has the peculiarity of possessing
both gills and a kind of lungs, the swim-bladder being surrounded with
a plexus of bloodvessels and taking on a respiratory function.
In all the higher vertebrates the respiration is carried on by lungs;
the trifling amount of gaseous interchange which can possibly take
place through the skin is not worth taking into account. The lungs
are to be regarded as developed from outgrowths of the alimentary
canal, beginning near the mouth.
22*
PRELIMINARY ANATOMICAL DATA 223
The object of all special respiratory arrangements being, in the first
instance, to facilitate the gaseous exchange between the surrounding
medium (air or water) and the blood, a prime necessity of a respiratory
organ, be it skin, gill, trachea, or lung, is a free supply of blood, in
vessels so fine and thin that diffusion readily takes place into them
and out of them. But a free supply of blood would be of no avail if the
medium to which the blood gave up its carbon dioxide and from which
it drew its oxygen was not being constantly and sufficiently renewed.
Sometimes the natural currents of the water or the air are of them-
selves sufficient to secure this renewal; in other cases, artificial currents
are set up by cilia, or special bailing organs, like the scaphognathites
of the lobster. In all the higher animals, active movements by which
air or water is brought into contact with the respiratory surfaces, are
necessary; and it is possible that such movements take place even in
the tracheae of insects and other air-breathing arthropoda. Fishes, by
rhythmical swallowing movements, take in water through the mouth
and pass it over the gills and out by the gill-slits, while the frog distends
its lungs by swallowing air.
Physiological Anatomy of the Respiratory Apparatus.— In man the
respiratory apparatus consists of a tube (the trachea) widened at its
upper part into the larynx, which contains the special mechanism of
voice, and communicates through the nose or mouth with the external
air. Below, the trachea divides dendritically into innumerable
branches, the ultimate divisions of which are called bronchioles. Each
bronchiole ends in several openings or vestibula, each of which in turn
leads into a dilatation called an atrium. From each atrium are given
off two, or more, often funnel-shaped diverticula, the infundibula, the
walls of which are everywhere pitted with recesses or alcoves, called
alveoli. The atria are also lined with alveoli. The infundibula (with
the atria) constitute the essential distensible elements of the lung, by
the alternate stretching and relaxation of which the respiratory changes
in the volume of the organ are mainly brought about. The trachea and
bronchi are strengthened by hyaline cartilage which renders them rela-
tively rigid. But the fact that the cartilage does not form complete
rings permits small changes of calibre to take place.
In the bronchioles, no cartilage is present, but the circularly-arranged
muscular fibres still persist, and also form a thin layer in the infundi-
bula. In the air-cells, or alveoli, however, there are no muscular fibres.
Their walls consist essentially of a network of elastic fibres, continuous
with a similar layer in the infundibula and bronchioles, and covered on
the side next the lumen by a single layer of large, clear epithelial scales,
with here and there a few smaller and more granular polyhedral cells.
From the larynx to the bronchioles the mucous membrane is ciliated
on its free surface, the cilia lashing upwards so as to move the secre-
tion towards the larynx and mouth. In the infundibula the ciliated
epithelium begins to disappear, and is absent from the alveoli. Part
of the nasal cavity and the upper part of the pharynx are also lined with
ciliated epithelium. Mucous glands are present in abundance in the
upper porticn; of the respiratory passages, but disappear in the smaller
bronchi.
Blood-Supply of the Lungs. — The quantity of blood traversing the
lungs bears no proportion to the amount required for their actual
nourishment. Small, however, as this latter quantity is, it cannot
apparently be derived from the vitiated blood of the right ventricle,
but is obtained directly from the aortic system by the bronchial arteries.
These are distributed with the bronchi, which they supply as well as
the connective tissue of the interlobuiar septa running through the
224 RESPIRA TION
substance of the lung, the pleura lining it and the walls of the large
bloodvessels. Most of the blood from the bronchial arteries is returned
by the bronchial veins into the systemic venous system, but some of it
finds its way by anastomoses into the pulmonary veins.
The branches of the pulmonary artery are also distributed with the
bronchi, and break up into a dense capillary network around the alveoli.
From the capillaries veins arise which, gradually uniting, form the large
pulmonary veins that pour their blood into the left auricle.
The same quantity of blood must, on the whole, pass per unit of
time through the lesser as through the greater circulation, otherwise
equilibrium could not exist, and blood would accumulate either in the
lungs or in the systemic vessels. But it does not follow that at each
heart-beat the output of the two ventricles is exactly equal. If, indeed,
the capacity of the lesser circulation were constant, the quantity
driven out at one systole by the right ventricle would be the same as
that ejected at the next by the left ventricle. But it is known that
the capacity of the pulmonary vessels is altered by the movements
of respiration and probably in other ways, so that it is only on the
average of a number of beats that the output of the two ventricles can
be supposed equal.
The time required by a given small portion of blood — e.g., by a single
corpuscle — to complete the round of the lesser circulation, is, as we
have seen (p. 137), much less than the average time needed to complete
the systemic circulation. In man the ratio is probably about i : 5.
Since all the blood in a vascular tract must pass out of it in a period
equal to the circulation time, the average quantity of blood in the
lungs and right heart of a man would thus be about one-fifth of that in
the systemic vessels. That is to say, not less than 700 grm. out of the
4^ kilos* of blood in a yo-kilo man would be contained in the lesser cir-
culation, and about 3^ kilos in the greater. This corresponds sufficiently
well with calculations from other data.
For example, the average weight of the lungs in three persons exe-
cuted by beheading,' was 457 grm. (Gluge). The average weight of
the lungs in a great number of persons who had died a natural death
was 1,024 grm. (Juncker). The weight of the pulmonary tissue alone
in the first set of cases must be less than 457 grm., for the lungs of a
person who has bled to death are never bloodless. In a dog killed by
bleeding from the carotid, one-quarter of the weight of the lungs con-
sisted of blood. Assuming the same proportion for the decapitated
individuals, we get 343 grm. as the net weight of the blood-free lungs.
Deducting this from 1,024 gmi., we arrive at 681 grm. as the average
quantity of blood in the lungs. Adding to this the quantity in the
right side of the heart (p. 140), we get, in round numbers, 750 grm.
as the amount in the lesser circulation. It is true that in the living
body the conditions are not the same as after death ; but it is probable
that in a large number of cases taken at random the differences would
be approximately equalized.
It has been further calculated that the total area of the alveolar
surface of the lungs of a man is about 100 square metres (sixty times
greater than the area of the skin), of which, perhaps, 75 square metres
are occupied by capillaries. The average thickness of this immense
sheet of blood has been reckoned to be equal to the diameter of a red
blood-corpuscle, or, say, 8 u. This would give 600 c.c. (630 grm.) as
the quantity of blood in tne lunge, which is probably somewhat too
low an estimate.
* See footnote on p, 139
MECHANICAL PHENOMENA OF EXTERNAL RESPIRATION 225
If we take the pulmonary circulation-time as 13 seconds (p. 137).
o* /"r x 60 x (3o
and the quantity of blood in the lungs as 700 grm., then -
= 194 kilos of blood will pass through the lungs in an hour, or 4,656
kilos (say, 4,400 litres) in twenty-four hours. This would fill a cubical
tank in which the man could almost stand upright with the lid closed.
SECTION II. — MECHANICAL PHENOMENA OF EXTERNAL
RESPIRATION.
The lungs are enclosed in an air-tight box, the thorax; or it may
be said with equal truth that they form part of the wall of the
thoracic cavity, arid the part which has by far the greatest capacity
of adjustment. The alveolar surface of the lungs is in contact with
the air. The pleura, which covers their internal surface, is reflected
over the chest-walls and diaphragm, so as to form two lateral sacs,
the pleural cavities. In health these are almost obliterated, and the
visceral and parietal pleurae, separated and lubricated by a few
drops of lymph, glide on each other with every movement of
respiration. But in disease the pleural cavities may be filled and
their walls widely separated by exudation, as in pleurisy, or by
blood, as in rupture of an aneurism, or by air in -the condition
known as pneumo-thorax. Between the two pleural sacs lies a mesial
space, tne mediastinum, commonly divided into an anterior medias-
tinum in front of the heart, and a posterior mediastinum behind it.
The pleural and pericardial sacs and the mediastinum constitute
together the thoracic cavity. The external surface of the chest-
wall and the alveolar surface of the lungs are subjected to the
pressure of the atmosphere, to which the pressure in the thoracic
cavity (intra-thoracic pressure) would be exactly equal if its bound-
aries were perfectly yielding. But in reality the intra-thoracic
pressure is always normally something less than this. For even
the lungs, the least rigid part of the boundary, oppose a certain
resistance to distension, and so hold off, as it were, from the thoracic
cavity a portion of the alveolar pressure; and in any given position
of the chest the intra-thoracic pressure is equal to the atmospheric
pressure minus this elastic tension of the lungs.
The object of the respiratory movements is the renewal of the air
in contact with the alveolar membrane — in other words, the ventila-
tion of the lungs. Two main methods are followed by sanitary
engineers in the ventilation of buildings: they force air in, or they
draw it in. In both cases the movement of the air depends on the
establishment of a slope of pressure from the inlet to the interior.
In the first method, this is done by increasing the pressure at the
inlet; in the second, by diminishing the pressure at the outlet. In
certain animals Nature, in solving its problem of ventilation, has
made use of the first principle. Thus, the frog forces air into its
15
226
RESPIRA TION
lungs by a swallowing movement. In artificial respiration, as
practised in physiological experiments, the same method is usually
employed: air is driven into the lungs under pressure. But in the
vast majority of air-breathing animals, including man, the opposite
principle has been adopted ; and the ' indraught ' of air from nose
and pharynx to alveoli is not set up by increasing the pressure in
the former, but by diminishing it in the latter. This ' indraught,'
or inspiration, is brought about by certain movements of the chest-
wall, which increase the capacity of the
thoracic cage and lower the pressure in the
thoracic cavity. The expansion of the
highly- distensible lungs keeps pace with
the diminution of pressure in the pleural
sacs, and they follow at every point the
retreating chest -wall and diaphragm,
although they do not expand equally in
all directions. The dorsal surface in con-
tact with the vertebral column, the
mediastinal surface in contact with the
pericardium and the contents of the
mediastinum, and the surface of the apex,
move but little. The surfaces in contact
with the diaphragm, ribs, and sternum
have the greatest range of movement.
Intermediate portions of the parenchyma
of the lungs expand in a degree determined
by their distance from the relatively
stationary and mobile surfaces. The pres-
sure of the air in the alveoli during the
rapid expansion of the lungs necessarily
sinks below that of the atmosphere, and
air rushes in through the trachea and
bronchi till the difference is equalized.
Then commences the movement of ex-
piration. The expanded chest falls back
to its original limits; the pressure in the
thoracic cavity increases; the distended
lungs, in virtue of their elasticity, shrink to their former volume;
the pressure of the air in the alveoli rises above that of the atmo-
sphere, and with this reversal of the slope of pressure air streams
out of the bronchi and trachea.
In inspiration the chest dilates in all its diameters. Its vertical
diameter is increased by the contraction of the diaphragm, which,
composed of a central tendon, a peripheral ring of muscular tissue,
and the two muscular crura, bulges up into the thorax in the form
of two flattened domes, one on each side, and thus closes its lowe*
Fig. 109. — Scheme to illus-
trate the Movements of the
Lungs in the Chest. T is
a bottle from which the
bottom has been removed;
D, a flexible and elastic
membrane tied on the
bottle, and capable of being
pulled out by the string S
so as to increase the ca-
pacity of the bottle. L is
a thin elastic bag repre-
senting the lungs. It com-
municateswith the external
air by a glass tube fitted
airtight through a cork in
the neck of the bottle.
When D is drawn down, the
pressure of the external air
causes L to expand. When
the string is let go, L con-
tracts again, in virtue of
its elasticity.
MECHANICAL PHENOMENA OF EXTERNAL RESPIRATION 227
aperture. When the diaphragm contracts, even in ordinary quiet
breathing, the central tendon descends distinctly (about half an
inch) after the manner of a piston. The acute angle which the
muscular ring makes during relaxation with the thoracic wall opens
out around its whole circumference, so as to form a groove of trian-
gular section. But the most peripheral portion of the ring is always
kept in close apposition to the chest-wall by the negative intra-
thoracie pressure. The lungs follow the descending diaphragm,
their lower borders keeping accurately in contact with it. The
descent of the diaphragm is not directly downwards, but downwards
and forwards. For it is compounded of two movements, the spinal
segment of the muscle (the crura) causing a vertical elongation of
the thorax, while the sterno-costal part (the muscular ring) pushes
the abdominal viscera downwards and forwards (Keith). Since
the diaphragm is attached to the lower ribs, there is a tendency
during its contraction for these to be drawn inwards and upwards;
but this is opposed by the pressure of the abdominal viscera, and by
the action of the quadratics lumborum, which fixes the twelfth rib,
and of the serratus posticus inferior, which draws the lower four
ribs backward. When these and the other inspiratory muscles
that act especially upon the ribs are paralyzed by injury to the
spinal cord, and respiration is carried on by the diaphragm alone,
the line of its attachment to the ribs is distinctly marked during
inspiration by a shallow circular groove.
The thorax is also enlarged by the action of certain muscles that
act upon the ribs. Among the elevators of the ribs, as their name
indicates, are usually reckoned, although erroneously, the levatores
costarum — twelve in number on each side. They arise from the
transverse processes of the last cervical and first eleven dorsal
vertebrae, and passing obliquely downwards and outwards, are in-
serted between the tubercle and the angle into the first or second rib
below their origin. They do not elevate the ribs, but take part in
lateral movements of the spinal column. The scalene muscles,
which may in a lean person be felt to be tense during inspiration,
fix the first and second ribs (scalenus anticus and medius, the first ;
scalenus posticus, the second rib), and so afford a fixed line for the
intercostal muscles to work from on the lower ribs.
The most important elevators of the ribs are the external inter-
costals. The intercartilaginous portions of the internal inter-
costals (the intercartilaginei muscles, as they are sometimes called)
also contract simultaneously with the diaphragm, and may there-
fore be included in the list of inspiratory muscles; but instead of
elevating the ribs they depress the costal cartilages, and 'thus help
to widen the angles between them and the ribs. In addition to
increasing the capacity of the chest, the contraction of the external
intercostals and the intercartilaginous muscles aids in inspiration
228 RESPIRATION
by augmenting the rigidity of the intercostal spaces, and so pre-
venting them from being drawn in as easily as would otherwise be
the case when the thorax is expanded by the action of the dia-
phragm and the other inspiratory muscles.
Leaving out of account the floating ribs, which functionally form
a part of the abdominal wall, the ribs in relation to their respiratory
functions may be divided into the following groups: (i) The first
rib, which, moving itself very little, provides a fixed line towards
which the next set of ribs may be raised.
(2) An upper costal series consisting of the ribs from the second
to the fifth. These are raised in inspiration towards the fixed first
rib by the contraction of the intercostal muscles. The movement
of these ribs is, mainly at any rate, a rotation around a transverse
axis, the axes on which they move corresponding to their necks.
The manner in which they are articulated to the vertebrae prevents
any sensible rotation around an antero-posterior axis or ' bucket-
handle ' movement. Since these ribs slant downwards and forwards
to their sternal attachments, the sternum is raised when they are
elevated; or, rather, since the manubrium is practically immovable
in ordinary breathing, the body of that bone is bent on the manu-
brium at the manubrio-sternal joint. This causes an increase in
the antero-posterior diameter of the thorax. Further, since the
arches formed by the ribs widen in regular progression from above
downwards in the upper portion of the thoracic cage, so that the
second rib is a segment of a larger circle than the first, and the
third than the second, it is clear that a general elevation of the chest
will tend to increase the transverse diameter at any given level.
Such an increase is also favoured by the opening out of the angles
between the bony ribs and the costal cartilages under the influence
of the couple (or pair of oppositely directed forces) that acts on them
— viz., the upward pull of the external intercostals exerted on the
ribs, and the downward pull of the intercartilaginei and the resist-
ance of the sternum to further displacement exerted on the carti-
lages. The whole arrangement is perfectly adapted to permit the
expansion of the roughly conical upper lobes of the lungs.
(3) The lower costal series, consisting of the ribs from the sixth
to the tenth. These ribs, with their muscles, form a mechanism
which normally acts along with the diaphragm (Keith). They are
so arranged that in inspiration the lateral and anterior part of
each moves outwards to a greater extent than the one above it.
There is not only a rotation around a transverse axis, by which the
lower end of the sternum, connected to these ribs by the combined
cartilages of the sixth to the ninth, is elevated, but also a rotation
around an antero-posterior axis. The movement of the lower ribs
results, therefore, in increasing both the back-to-front diameter and
the transverse diameter of the lower portion of the thorax. The
MECHANICAL PHENOMENA OF EXTERNAL RESPIRATION 229
widening of the thorax from side to side may also be in a slight
degree ascribed to a twisting movement of the ribs, which tends to
evert their lower borders. With the diaphragm, these lower ribs
arranged in a vertical series of not very different curvature con-
stitute a mechanism for the inspiratory expansion of the roughly
cylindrical lower lobes of the lungs.
Expiration in perfectly tranquil breathing is brought about with
less aid from active muscular contraction. The sense of effort
disappears as soon as the chest ceases to expand. The diaphragm
and the elevators of the ribs relax. The structures that have been
stretched or twisted recoil into their original positions; the struc-
tures that have been raised against the force of gravity fall back
by their weight, and in the measure in which the pressure increases
in the thoracic cavity the elasticity of the lungs causes them to
shrink. The pressure in the alveoli, which at the end of inspiration
was just equal to that of the atmosphere, is thus increased, and the
air expelled. It is probable that, even in man and in quiet respira-
tion, the interosseous portions of the internal intercostals help by
their contraction in depressing the ribs, and that a slight contrac-
tion of the abdominal muscles hastens the return of the diaphragm
to its position of rest. In reptiles and birds, expiration is normally
effected by an active muscular contraction. This is also true in
some mammals — the rabbit, for instance, in which the external
oblique muscles of the abdominal wall take an important share in
the expiratory act.
Types of Respiration. — Differences exist also, not only between
different groups of animals, but even between women and men, in
the relative importance in inspiration of the diaphragm and the
muscles that raise the lower ribs on the one hand, and the muscles
that elevate the upper ribs on the other. When the movements of
the diaphragm predominate, the respiration is said to be of the
abdominal or diaphragmatic type ; when the movements of the upper
ribs and sternum are most conspicuous, of the costal or thoracic type.
In abdominal respiration, the inspiratory movement commences at
the diaphragm, and then involves the lower ribs and the tip of the
sternum. In costal respiration, the upper ribs initiate the move-
ment, and are followed by the abdomen. In the rabbit, during
quiet breathing, the respiration is purely diaphragmatic, the ribs
remain motionless; and herbivorous animals in general conform
more or less closely to this type. In the carnivora, on the contrary,
the costal type prevails. Man allies himself as regards his respira-
tion with the rabbit and the sheep ; he uses his diaphragm more than
his upper ribs. Civilized woman falls into the class of the wolf and
the tiger; she uses her upper ribs more than her diaphragm. The
cause of the difference between men and women has been much
discussed. It is not a primitive sexual difference, for it is far from
23o RESPIRATION
being universal; in the uncivilized and semi-civilized races that
have been investigated, the women breathe like the men. It is
therefore probable that the predominance of the costal type among
women of European race is a peculiarity developed by a mode of
dressing which hampers the movements of the diaphragm \vhilc
permitting the elevation of the ribs. This conclusion is strengthened
by the fact that in children no difference exists ; both boys and girls
show the abdominal type of respiration.
All this refers to ordinary breathing. In forced respiration, when
the need for air becomes urgent, costal breathing always becomes
prominent alike in men, in women, and in animals, for by elevation
of the ribs the capacity of the chest can be increased to a greater
degree than by any contraction of the diaphragm.
In forced inspiration, indeed, all the muscles that can elevate the
ribs may be thrown into contraction, as well as other muscles which
give these fixed points to act from. During a paroxysm of asthma,
for example, the patient may grasp the back of a chair with his
hands, so as to fix the arms and shoulders and allow the pectorals
and serratus magnus to raise the ribs. Similarly in forced expiration
all the muscles are used which can depress the ribs, or increase the
intra-abdominal pressure and push up the diaphragm.
Artificial Respiration. — An efficient pulmonary ventilation can be
obtained by various methods when the natural breathing is in abey-
ance. In animals the method most commonly employed for ex-
perimental purposes is the rhythmical inflation of the lungs by a
pump or bellows, or by a stream of compressed air which is regularly
interrupted, the chest being allowed to collapse after each inflation.
When the animal is to be kept alive after the experiment the inflation
is produced through a tube introduced through the glottis. If the
animal is not to be kept alive, the apparatus is generally connected
with a cannula in the trachea. When it is desired to avoid move-
ments of the lungs, respiration may be maintained by a stream of
oxygen through a catheter passed down the trachea (method of
insufflation). In man the exchange of air between the atmosphere
and the lungs may be most readily accomplished by strong rhythmi-
cal compression of the lower part of the chest. This forces out
some of the air from the lungs; on relaxing the pressure the chest
expands again and air is drawn in. Schafer has shown that this is
the most efficient method of respiration in resuscitation of the ap-
parently drowned. ' The patient is placed face downwards on the
ground, with a folded coat under the lower part of the chest. The
operator puts himself athwart or at the side of the patient, facing his
head and kneeling upon one or both knees (Fig. no), and places his
hands on each side over the lower part of the back (lowest ribs) . He
then slowly throws the weight of his body forward to bear upon his
own arms, and thus presses upon the thorax and forces air out of
the lungs. He then gradually relaxes the pressure by bringing his
MECHANICAL PHENOMENA OF EXTERNAL RESPIRATION 231
own body up again to a more erect position, but without moving
the hands.' Air is thus drawn into the lungs. The process is
repeated twelve to fifteen times a minute.
Certain accessory phenomena (movements and sounds) are asso-
ciated with the proper movements of respiration. The larynx rises
in expiration, and sinks in inspiration. The glottis (and particu-
larly its posterior portion, the glottis respiratoria) is widened during
deep inspiration and narrowed during deep expiration. The same
is the case with the nostrils, and, indeed, iri some persons the alae
nasi move even in ordinary breathing. It has long been known
that in deep respiration changes in the calibre of the bronchi syn-
chronous with the respiratory movements may occur. In young
persons it may be directly observed with the bronchoscope, an
instrument used by laryngologists for exploring the larger bronchi,
that these dilate
in inspiration
and constrict in
expiration (In-
galls). In part
at least these
movements are
passively pro-
duced by the
changes of intra-
thoracic pres-
sure, but it has
not been defi-
nitely deter-
mined whether
they are not in
part caused by
alternate contraction and relaxation of the circular bronchial
muscles. To these muscles has sometimes been attributed the
function of regulating the flow of air into and out of the infundib-
ula, as the muscle of the arterioles regulates the distribution of the
blood in the organs.
As regards the respiratory sounds, all that is necessary to be said
here is that when we listen over the greater portion of the lungs with
the ear, or, much better, with a stethoscope, a soft breezy murmur,
that has been compared to the rustling of the wind through distant
trees, is heard. This has been called the vesicular murmur. It is only
heard in health during inspiration and the very beginning of expira-
tion, and is louder in children than in adults. Around the larger
bronchi and the trachea a blowing sound is heard, which certainly
originates at the glottis, and is strengthened by the resonance of the
air-tubes. In health this is not recognized over the greater portion of
the lung. But in certain diseases in which the alveoli are devoid of
air, whether from compression or because they are filled up with
exudation, and in other conditions, this bronchial or tubular breathing
Fig. no. — Artificial Respiration in Cases of Drowning (after
Schafer).
232 RESPIRATION
may be heard over the affected area. The bronchi themselves, how-
ever, must still be patent and contain air. The most commonly
accepted explanation is that the laryngeal sound is better conducted
through the smaller bronchi towards the surface of the lungs when
their walls have been rendered more rigid by the solidification of the
parenchyma, in spite of the fact that the consolidated tissue as such
docs not conduct the sound so well as the air-containing alveoli. It
seems probable that, in addition, the columns of air in the bronchi,
which arc encased in solid tissue, may actually increase the intensity
of the transmitted laryngeal murmur by resonance.
It has been much debated whether the vesicular murmur also arises
at the glottis, and is modified by transmission through the pulmonary
tissue, or whether it arises somewhere in the terminal bronchi, the
infundibula or the alveoli. Both views may be supported by certain
arguments, and to both some objections may be raised, 'the fact
appears to be that there are two elements in the inspiratory murmur —
a true vesicular sound, produced about the place where the terminal
bronchioles give off the infundibula, and a resonance sound set up in
the trachea and bronchi by the glottic murmur. This resonance sound
as heard over portions of the lung containing only small bronchi has
a different character from that heard over large bronchi, inasmuch as
the fundamental note, and to a still greater extent the overtones
]p. 310), are much weakened in those small and easily-distensible
tubes. The true vesicular element is heard all over the lungs, but
the resonant laryngeal element in large animals, like the horse and ox,
dies out as an audible murmur before it reaches the remotest lobules,
and can only be distinguished over a portion of the pulmonary area.
When the glottic sound is eliminated by causing an animal to breathe
through a tracheal fistula, the vesicular murmur is still heard, and in
the horse is even somewhat sharper than normal, although in the dog
it is softer and weaker. The expiratory murmur does not seem to
contain a true vesicular element, but is exclusively due to the resonance
of the expiratory glottic sound (Marek). It is ge'nerally admitted, and
this is of great importance in practical medicine, that when the normal
vesicular sound is heard over any portion of the lung tissue, it may be
inferred that this portion is. being properly distended, and that air is
freely entering its alveoli.
Up to this point we have contented ourselves with a purely
qualitative description of the mechanical phenomena of respiration.
We have now to consider their ^ quantitative relations, and the
methods by which these have been studied.
The expansion of the lungs in inspiration may be easily demonstrated
in man, and even a rough estimate of its amount obtained, by the clinical
method of percussion. For example, the resonant note that is elicited
when a finger laid on the chest at a part where it overlies the right
lung is smartly struck can be followed down until it is lost in the ' liver
dulness.' If the lower limit of the resonant area be marked on the
chest -wall first in full inspiration, and then in full expiration, the mark
will be lower in the former than in the latter, and the difference will
represent the difference in the vertical length of the shrunken and dis-
tended lung. A similar enlargement in the transverse direction may
be demonstrated in the same way, the inner borders of the lungs coming
nearer to the middle line in inspiration, and receding from it in expira-
tion. The examination of the chest by the Rontgen rays has also
MECHANICAL PHENOMENA OP EXTERNAL RESPIRATION 233
yielded results of importance in the study of normal respiratory con-
ditions, and still more important results in pulmonary disease.
For most physiological purposes, however, a faithful graphic record
of the respiratory movements is indispensable. This may be obtained —
(1) By registering the movements
of a single point, or the variations in
a single circumference, of the bound-
ary of the thoracic cavity. In man
changes in the circumference of the
thorax at any level can be recorded
by means of a tambour adjusted to
the chest (Figs, in and 134), and in
communication with another, which
is provided with a writing lever
(Figs. 99 and 137). Or an elastic
tube, with a spiral spring in its
lumen, may be fastened around the
thorax or abdomen and connected
with a piston-recorder (a small cylin-
der in which works a piston carrying
a writing-point) (Fitz).
(2) By recording the changes of
pressure produced in the air-passages
by the respiratory movements. This
can be done by connecting a cannula
in the trachea of an animal with a
recording tambour in the manner
described in the Practical Exercises
(p, 3oo). The variations of pressure
may be measured by connecting a
manometer with the trachea, or in
man with the nostril.
(3) ; By writing off the changes of pressure which occur in the thoracic
cavity during respiration. For this purpose a trocar (Fig. 113) is intro-
duced through an intercostal space into one of the pleural sacs, without
the admission of air, or into the pericardium, and then connected with
a manometer or other recording apparatus. Or a tube, similar in con-
struction to a car-
diac sound (p. 96),
may be pushed
down the cesopha-
gu?. The varia-
tions in the intra-
thorrxic pressure
are transmitted to
the air in the elas-
tic bag, and thence
to a tambour.
(4) In the rabbit
the part of the dia-
phragm attached to the ensiform cartilage may be isolated from the
rest and its contractions recorded by a lever (Head). For scone purposes
this is the best method.
When the respiratory movements are studied in any of these ways,
it is found that there is practically no pause between the end of
Fig. in. — Scheme of Tambour for
recording Respiratory Movements.
C, a metal capsule connected airtight
with B, A, two caoutchouc mem-
branes, the chamber formed by which
can be inflated by means of the tube
and stopcock E. The tube D con-
nects the space H with a registering
tambour provided with a lever. The
membrane A is applied to the chest,
round which the inextensible strings
Fare tied. At every expansion of the
chest the pressure in H is increased,
and the increase of pressure is trans-
mitted to the registering tambour.
Fig. ii2.— Respiratory Tracing from Man (Marey). Down
stroke, inspiration; up stroke, expiration.
234
RESPIRATION
inspiration and the beginning of expiration. Nor, although the
chest collapses more gradually than it expands, is there any distinct
interval in ordinary breathing between the end of expiration and
the beginning of the succeeding inspiration. When, however, the
respiration is unusually slow, an actual pause (expiratory pause)
may occur at this point. Expiration takes
somewhat longer time than inspiration, the
ratio varying from 7 : 6 to 3 : 2, according to
age, sex, and other circumstances.
The frequency of respiration is by no means
constant even in health. All kinds of in-
fluences affect it. It is difficult even to direct
the attention to the respiratory act without
bringing about a modification in its rhythm.
In the adult 15 to 20 respirations per minute
may be taken as about the normal. In young
children the frequency may be twice as great
(new-born child, 50 to 70; child from i to 5
years old, 20 to 30 per minute). It is greater
in a female than in a male of the same age. A
rise of temperature increases it; 150 respira-
tions per minute have been seen in a dog with
a high temperature. Sudden cooling of the skin,
exercise, and various emotional states, increase
the rate, and sleep diminishes it. The will can
alter the frequency and depth of respiration
for a time, and even stop it altogether, but in
less than a minute, in ordinary individuals, the
desire to breathe becomes imperative. Cato's
assertion that he could kill himself at any time
' merely by holding his breath ' is only a proof
that he was a better philosopher than physi-
ologist. After a period of forced respiration
the breath can be held for a much longer time.
This is due to the ' washing out ' of the carbon
dioxide, the normal stimulus to the respiratory
centre (p. 281). After six minutes of forced
breathing the interval of voluntary inhibition can be extended be-
yond four minutes. A professional diver has remained under water
in a tank for about four and three-quarter minutes. When oxygen
is inhaled instead of air during the last few breaths of the forced
respiration, the interval during which the breath can be held may
be much increased (up to nine or ten minutes). In animals the rate
of respiration can be greatly affected by drugs and by the section
and stimulation of certain nerves ; but to this we shall return when
we come to consider the nervous mechanism of respiration.
L--
Fig. 113. — Simple
Pleural Cannula. B,
a line of small spurs
which, after the can-
nula C has been
pushed without ad-
mission of air through
an intercostal space
into the pleural
cavity, stick in the
parietal pleura and
securely fasten the
cannula. Traction
being made on the
cannula, a ligature is
tied at L around the
protruding tissue for
greater security. S,
side-tube by which the
cannula is connected
with a manometer or
tambour.
MECHANICAL PHENOMENA OF EXTERNAL RESPIRATION 235
It cannot fail to be observed that to a great extent the rate of
respiration is affected by the same circumstances as the frequency
of the heart (p. 107), and in the same direction. And, indeed, in
health, these two physiological quantities, amid all their absolute
variations, maintain to each other a fairly constant ratio (i to 4 or
f _ -.._._ i to 5 in man). Even in many diseases
this proportion remains tolerably
stable, although in others it is dis-
turbed.
The total quantity of air expired, or,
what comes to the same thing, the
alteration in the capacity of the chest
during expiration, can be measured by
means of a gas-meter or of a spiro-
meter (Fig. 114), which consists of an
inverted graduated glass cylinder dip-
ping by its open mouth into water
and balanced by weights. The vessel
is sunk till it is full of water, the air
being allowed to escape by a cock.
The expired air is now permitted to
enter it through a tube, and displaces
some of the water. The spirometer
is adjusted so that the level of the
water inside and outside is the same,
and then the volume of air contained in it is read off. This gives
the volume of the expired air at atmospheric pressure. Similarly,
by breathing air from the spirometer the amount inspired can be
measured (p. 303).
From 400 to 500 c.c. of air* are taken in and given out at each
respiration in quiet breathing. This is called tidal air. It amounts
to 35 pounds by weight
I
Fig. 114. — Diagram of Spirometer.
A, vessel filled with water. B,
glass cylinder with scale C,
swung on pulleys and counter-
poised by weights W. D, tube
for breathing through.
Vital
Copacit(j\
ear
Tidal _..
Supplemental air
Residual air
Fig. 115. — Diagram to illustrate the Relative Amount
of Complemental, Tidal, Supplemental, and Residual
Air.
in twenty-four hours,
or enough to fill, at
atmospheric pressure,
a cubical box with a
side of 8 feet. With
the deepest possible in-
spiration room can be
made for 2,000 c.c. more ; this is called complemental air. By a forced
expiration 1,500 c.c. can be expelled besides the tidal air ; and to this
* The average for 81 healthy students, with an average body-weight of
66 kilos, was 460 c.c., or 7 c.c. per kilo. In 4 new-born children the tidal air
varied from 20 to 30 c.c., and from y6 to 7' 3 c.c. per kilo, which is not very
different from the amount in the adult. The pulmonary ventilation must
therefore be far more rapid in the child, since its respiratory frequency is so
much greater.
236 RESPIRA TION
quantity the name of supplemental or reserve air has been given.
After the deepest expiration there always remains 1,000 to 1,200 c.c.
of air in the lungs (Durig), and this is called the residual air. After
a normal expiration following a normal inspiration the lungs still
contain stationary air to the amount of about 2,500 c.c.
The term vital or respiratory capacity is applied to the quantity
of air which can be expelled by the deepest expiration following the
deepest inspiration, and amounts in an adult of average height to
3,500 or 4,000 c.c. The maximum quantity of air which the lungs
can contain is evidently equal to vital capacity plus residual air.
At one time the vital capacity was thought to be capable of affording
valuable information in the diagnosis of chest diseases; but little
stress is now laid upon it, as it varies from so many causes. For
instance, it can be increased by practice with the spirometer. It is
greater in mountaineers than in the inhabitants of lowland plains.
The Dead Space. — It is clear from the figures we have given that in
ordinary breathing only a small proportion of the air in the lungs
comes in direct at each inspiration from the atmosphere, and only a
small proportion escapes into the atmosphere at each expiration.
The greater part of the air in the lungs is simply moved a little farther
from the upper respiratory passages, or a little nearer them; and
fresh oxygen reaches the alveoli, as carbon dioxide leaves them,
mainly by diffusion, aided by convection currents due to inequali-
ties of temperature, and to the churning which the alternate expan-
sion and shrinking of the lungs, and the pulsations of their arteries
must produce. But that some of the tidal air strikes right down
to the alveoli is evident enough. For the respiratory ' dead space '
— that is, the capacity of the upper air-passages and the bronchial
tree down to the infundibula — is only 140 c.c., or one-third of the
amount of the tidal air (Zuntz, Loewy). There is no direct way of
determining whether any respiratory exchange goes on through the
walls of the upper air-passages. But by indirect methods it has
been estimated that about 30 per cent, of the volume of the tidal air
is pure air (Haldane and Priestley). This, of course, corresponds
to the ' effective ' dead space. Taking the average tidal air at
460 c.c. (p. 235), it is clear that the effective corresponds very closely
with the anatomical dead space— that is to say, the respiratory
function of the air-passages above the point where the infundibula
are given off is negligible. Although such calculations can only b2
approximately correct, the agreement is of interest. Some observers
have stated that great variations occur in the size of the dead space
with changes in the depth of respiration, its volume being increased
four or even eight times by very deep breathing. This, however,
is incorrect, although with maximum expansion of the lungs the
increase may amount to 100 c.c. (Krogh and Lindhard, Pearce).
The Amount and Variations of the Intrathoracic Pressure. — In
the deepest expiration the lungs are never completely collapsed ; their
MECHANICAL PHENOMENA OF EXTERNAL RESPIRATION 237
elastic fibres are still stretched; and the tension of these acts in the
opposite direction to the external atmospheric pressure, and dimin
ishes by its amount the pressure inside the thoracic cavity. In th^
dead body Bonders measured the value of this tension, and there-
fore of the negative pressure of the thorax, by tying a manometer
into the trachea, and then causing the lungs to collapse by opening
the chest. It varied from 7-5 mm. of mercury in the expiratory
position to 9 mm. in the inspiratory. So far as can be judged from
observations made on persons suffering from various diseases of the
respiratory organs, the alterations during ordinary breathing do not
Fig. 116. — Variations of Intraihoracic Pressure. Upper curve>*carotid blood-pres-
sure (dog) lower curve, intrapleural pressure. At 42 the trachea was closed ;
the blood-pressure curve shows the rise of asphyxia, and the intrapleural curve,
greatly exaggerated pressure variations due to the strong and slow but abortive
respirations.
amount to more than 3 or 4 mm. of mercury. But when an attempt
is made in the dead body to imitate a deep inspiration by making
traction on the chest walls so as to expand the lungs, the intra-
thoracic pressure may fall to —30 mm. of mercury; and in a living
rabbit, during a deep natural inspiration, a pressurs of —20 mm.
has been seen.
The reason why the lungs collapse when the chest is opened is
that the pressure is now equal on the pleural and alveolar surfaces,
being in both cases that of the atmosphere. There is therefore
nothing to oppose the elasticity of the lungs, which tends to con-
tract them. So long as the chest is unopened, the pressure on the
pleural surface of the lunge is less than that on the alveolar surface
238 RESPIRATION
and the elastic tension can only cause them to shrink until it just
balances this difference.
In intra-uterine life, and in stillborn children who have never
breathed, the lungs are completely collapsed (atelectatic), and there
is no negative intrathoracic pressure. They are kept in this con-
dition by adhesion of the walls of the bronchioles and alveoli. If
the lungs have been once inflated, this adhesion ceases to act, and
they never completely collapse again.
Amount and Variations of the Respiratory or Intrapulmonary
Pressure. — As we have already remarked, the pressure in the alveoli
and air-passages is less than that of the atmosphere while the in-
spiratory movement is going on, greater than that of the atmosphere
during the expiratory movement, and equal to that of the atmo-
sphere when the chest-walls are at rest. When the external air-
passages are closed — e.g., by connecting a manometer with the
mouth and pinching the nostrils — the greatest possible variations
of pressure are produced. In the deepest inspiration under these
conditions a negative pressure of about 75 mm. of mercury (i.e., a
pressure less than that of the atmosphere by this amount) has been
found, and in deep expiration a somewhat greater positive pressure*
(Practical Exercises, p. 304).
But with ordinary breathing, the variations of pressure as
measured by this method do not exceed 5 to 10 mm. of mercury
above or below the pressure of the atmosphere.
When the external openings are not obstructed, as, for example,
when the lateral pressure is taken in the trachea of an animal by
means of a cannula with a side-tube connected with a manometer,
still smaller, and doubtless truer, values have been found (2-3 mm.
of mercury as the positive expiratory pressure and i mm. as the
negative inspiratory pressure in dogs). But since the respiratory
passages are abruptly narrowed at the glottis, the variations of
pressure must be greater below than above it, and in general they
must increase with the distance from that orifice, being greater, for
instance, in the alveoli than in the bronchi.
The mechanical phenomena of respiration having been described,
it might seem logical to consider next the nervous mechanism by
which the respiratory movements are controlled ; but the regulation
of these movements through the nervous system is in so important
a degree a chemical regulation that it cannot be properly understood
without some knowledge of the chemical changes in the blood
associated with external and internal respiration. We therefore
pass to the consideration of —
* The maximum negative pressure in deepest inspiration averaged for 49
students -73 mm. (highest observation -137 mm.) of mercury; the maxi- »
mum positive pressure in deepest expiration, -f- So mm. (highest observation '
+ 140 mm.).
THE CHEMISTRY OF EXTERNAL RESPIRATION 239
SECTION III. — THE CHEMISTRY OF EXTERNAL RESPIRATION.
Our knowledge of this subject has been entirely acquired in the
last 200 years, and chiefly in the last century.
Boyle showed by means of the air-pump that animals die in a
vacuum, and Bernouilli that fish cannot live in water from which
the air has been driven out by boiling.
Mayow, of Oxford, seems to a considerable extent to have antici-
pated Black, who in 1757 demonstrated the presence of carbonic
acid (carbon dioxide) in expired air by the turbidity which it causes
in lime-water.
A fundamental step was the discovery of oxygen by Priestley in
1771, and his proof that the venous blood could be made crimson,
like arterial, by being shaken up with oxygen.
Lavoisier discovered the composition of carbonic acid, and applied
his discovery to the explanation of the respiratory processes in
animals, the heat of which he showed to be generated, like that of a
candle, by the union of carbon and oxygen. He made many further
important experiments on respiration, publishing some of hi 3 results
in 1789, when the French Revolution, in which he was to be one of
the most distinguished victims, was breaking out. He made the
mistake, however, of supposing that the oxidation of the carbon
takes place in the blood as it passes through the lesser circulation.
That some carbon dioxide is formed in the lungs there is no reason
to doubt, and the quantity may even be considerable. But that
they are not the chief seat of oxidation was sufficiently proved as
soon as it was known that the blood which comes to them from the
right heart is rich in carbon dioxide, while the blood which leaves
them through the pulmonary veins is comparatively poor.
There are two main lines on which research has gone in trying to
solve the chemical problems of respiration: (i) The analysis and
comparison of the inspired and expired air, or, in general, the in-
vestigation of the gaseous exchange between the blood and tho air
in the lungs. (2) The analysis and comparison of the gases of
arterial and venous blood, of the other liquids, and of the solid
tissues of the body, with a view to the determination of the gaseous
exchange between the tissues and the blood. We shall take these
up as far as possible in their order.
The methods which have been used for comparing the composi-
tion of inspired and expired air and estimating the respiratory ex-
change are verv various.
(i) Breathing into one spirometer and out of another, the inspired
and expired air being directed by valves. The contents 'of the spiro-
meters are analyzed at the end of the experiment (Speck). In the
arrangement of Zuntz and Geppert, instead of the whole of the expired
air, a sample is collected for analysis during the entire duration of the
experiment, while the total volume expired is measured by a gas-meter.
This is a very convenient method for observations on man, especially
24o RESPIRATION
in disease, but each experiment can only be carried on at most for
fifteen to twenty minutes.
(2) A small apparatus, much on the same principle, was used for
rabbits by Pfliiger and his pupils. A cannula in the trachea was con-
nected with a balanced and self-adjusting spiro meter containing oxygen,
and the inspired and expired air separated by potassium hydroxide
valves, which absorbed the carbon dioxide. The amount of oxygen
used could be read off on the spirometer, and the amount of carbon
dioxide produced estimated in the liquid of the valves.
(3) Elaborate arrangements, such as Pettenkofer's great respiration
apparatus, and the still larger and more efficient modifications of it
constructed since his time, in which a man, or even several men, can
remain for an indefinite period, working, eating, and sleeping: Air is
drawn out of the chamber by an engine, its volume being measured
by a gas-meter. But as it would be far too troublesome to analyze
the whole of the air, a sample stream of it is constantly drawn off, which
also passes through a gas-meter, through drying-tubes containing
sulphuric acid, and through tubes filled with baryta water. The baryta
solution is titrated to determine the quantity of carbon dioxide; the
increase in weight of the drying tubes gives the quantity of aqueous
vapour. A similar sample stream of the air before it passes into the
chamber is treated exactly in the same way, and from the data thus got
the quantity of carbon dioxide and aqueous vapour given off can readily
be ascertained. The oxygen can be calculated, as the difference be-
tween the final body-weight and the original body-weight plus the
weight of the carbon dioxide and water eliminated, but may also be
directly estimated by special methods.
(4) Haldane and Pembrey have elaborated a gravimetric method,
which is very suitable for small animals. It depends upon the absorp-
tion of carbon dioxide by soda lime. (See Practical Ex'ercises, p. 30%)
In Atwater's so-called respiration calorimeter, which will be referred to
again under ' Animal Heat,' and by which, not only the gaseous metab-
olism, but the heat production can be measured in man, the carbon
dioxide is estimated in the same way.
Inspired and Expired Air. — The expired air is at or near the body
temperature, and is saturated with watery vapour. In ordinary
breathing it contains about 4 per cent, of carbon dioxide, while the
inspired air only contains a trace. The expired air contains 16 or
17 per cent, of oxygen, the inspired air about 21 per cent. There are
in addition in expired air small quantities of hydrogen and marsh-
gas derived from the alimentary canal, either directly from eructa-
tion or after absorption into the blood. Sometimes a trace of
ammonia can be detected in the air of expiration, but this is due to
decomposition of proteins taking place in the mouth, especially in
carious teeth, or in the air-passages and lungs in disease of these
organs. It has indeed been shown that the lungs are practically
impermeable for ammonia. Expired air is entirely free from float-
ing matter (dust), which is always present in the inspired air. The
volume of the expired air, owing to its higher temperature and ex-
cess of watery vapour, is somewhat greater than that of the inspired
air, but if it be measured at the temperature and degree of satura-
tion of the latter, the volume is somewhat less. Since the oxygen
of a given quantity of carbon dioxide would have exactly the same
THE CHEMISTRY OF EXTERNAL RESPIRATION 24i
volume as the carbon dioxide itself at a given temperature and
pressure, it is clear that the deficiency is due to the fact that all the
oxygen which is taken up in the lungs is not given off as carbon
dioxide. Some of it, going to oxidize hydrogen, reappears as water.
Alveolar Air. — The percentage of carbon dioxide in the air of the
alveoli is of course greater and that of oxygen less than in the
ordinary expired air. For the relatively pure air of the dead-space
makes up a substantial fraction of the tidal air. The mean of the
oxygen or carbon dioxide percentages in samples taken from the
last portions of the air of two deep expirations, one following an
ordinary inspiration and the other following an ordinary expiration,
corresponds fairly well with the mean percentage in the alveoli
during ordinary breathing. This method becomes untrustworthy
during muscular work. The average percentage of oxygen may
be taken as 14*5, corresponding to a partial pressure (p. 248)
of 109 mm. of mercury. The percentage of carbon dioxide in
the alveolar air with the body at rest is remarkably constant in one
and the same individual at constant atmospheric pressure. It
varies in different men from 4-6 to 6*2 (mean 5-5) per cent, of the dry
alveolar air. In women and in children of both sexes it is less than
in men. From this we conclude that in men the partial pressure
of carbon dioxide in the alveoli may be at least one-eighteenth of
an atmosphere, or 42 mm. of mercury (Fitzgerald and Haldane).
Respiratory Quotient. — The quotient of the volume of oxygen
given out as carbon dioxide by the volume of oxygen taken in is
the respiratory quotient. It shows what proportion of the oxygen
is used to oxidize carbon. It may approach unity on a carbo-hydrate
diet which contains enough .ox^gyen to oxidize all its own hydrogen
to water. With a diet rich in fat it is least of all; with a diet of
lean meat it is intermediate in amount. For ordinary fat contains
no more than one-sixth, and proteins not one-half, of the oxygen
needed to oxidize their hydrogen (p. 620). In man on a mixed diet
the respiratory quotient may be taken as 0-8 or 0-9. So long as the
type of respiration is not .changed, the respiratory quotient may
remain constant for a wide range of metabolism. In hibernating
animals, however, the respiratory quotient may become very small
during winter sleep (as low as> 0-25), both the output of carbon
dioxide and the consumption of oxygen falling enormously, but
the former in general more than the latter. This has been explained
on the assumption that oxygen is stored away in winter sleep in the
form of incompletely oxidized substances. On the other hand, in
dyspnoea accompanying muscular exertion the respiratory quotient
has been found as high as 1-2. It must be remembered that even
a voluntary increase in the respiratory movements causes an imme-
diate temporary increase in the respiratory quotient, owing to the
' washing out ' of carbon dioxide from the blood and tissues. This
change has no metabolic significance. Indeed, the determination
16
of the respiratory quotient for short periods has only a limited
value, and such observations must be interpreted with great care.
In starvation the respiratory quotient diminishes, the production
of carbon dioxide falling off at a greater rate than the consumption
of oxygen, for the starving organism lives on its own fat and pro-
teins, and has only a trifling carbo-hydrate stock to draw upon.
In a diabetic patient, fed on a diet of fat and protein alone, the
respiratory quotient was only 0-6 to 07, just as in a starving man.
Total Respiratory Exchange. — The amount of oxygen absorbed in
a man at rest has been determined under certain conditions as about
0-29 gramme per hour, and the discharge of carbon dioxide as about
°'33 gramme per hour per kilogramme of body- weight. In an
average man weighing 70 kilos the mean production of carbon
dioxide is about 800 grammes (400 litres) in twenty-four hours, and
the mean consumption of oxygen about 700 grammes (490 litres).
But there are very great variations depending upon the state of the
body as regards rest or muscular activity and on other circum-
stances. In hard work the production of carbon dioxide was found
to rise to nearly 1,300 grammes, and in rest to sink to less than
700 grammes, the consumption of oxygen in the same circumstances
increasing to nearly 1,100 grammes and diminishing to 600 grammes.
In rest, in moderate exertion, and in hard work, the production of
carbon dioxide was found to be nearly proportionate to the numbers
2, 3, and 6 respectively. When unaccustomed work is performed,
the increase in the carbon dioxide output (and oxygen intake) may
be much greater. With training it diminishes. In a case of diabetes
the consumption of oxygen was 50 per cent, greater than in a healthy
man, corresponding to the higher heat-equivalent of the food of
the diabetic patient.
Ventilation. — Taking 400 litres per twenty-four hours, or 17 litres
per hour, as the mean production of carbon dioxide by an average male
adult at rest or doing only light work, we can calculate the quantity of
fresh air which must be supplied to a room in order to keep it properly
ventilated.
It has been found that when the carbon dioxide given off in respiration
amounts to no more than 2 parts in 10,000 in the air of an ordinary
room, the air remains sweet. When the carbon dioxide given off reaches
4 parts in 10,000, the room feels distinctly, and at 6 in 10,000 disagree-
ably, close, while at 9 parts in 10,000 it is oppressive and almost in-
tolerable. This is not due to the carbon dioxide as such, for pure
carbon dioxide added alone in similar proportions to the air of a room
has not the same bad effect, and the amount of this gas is only taken
as an index of the extent to which the air has been vitiated by some
other products or processes connected with the occupation of the
room. Very often the mere rise of temperature in a crowded and ill-
ventilated space is sufficient to induce disagreeable symptoms, especially
as it is inevitably associated with an ijncrease in the humidity of the
air, which reduces the capacity of the body to cool itself by increasing
the secretion of sweat. Thus it has been found that persons in a
respiratory chamber feel quite comfortable with only moderate ventila-
tion when the carbon dioxide has risen to i per cent., if care is taken
THE CHEMISTRY OF EXTERNAL RESPIRATION 243
that the temperature and the proportion of watery vapour do not rise
too high. In addition, however, it has been supposed by some that a
volatile poison exhaled from the lungs is peculiarly responsible for the
evil effects. Certain observers, indeed, alleged that the condensed
vapour of the breath, when injected into rabbits, produced fatal symp-
toms. But this has been shown to be erroneous; and the most careful
experiments have failed to detect in the air expired by healthy persons
any trace of such a poison. It has therefore been suggested that the
odour and some of the other ill-effects of a close room are due to sub-
stances given off in the sweat and the sebum, and allowed by persons
of uncleanly habits to accumulate on the skin, and also to the products
of slow putrefactive processes constantly going on, under favourable
conditions, on the walls, floor, or furniture, but only becoming per-
ceptible to the sense of smell when ventilation is insufficient. In a
small, newly-painted chamber, presumably free from such impurities,
it was not until the carbon dioxide reached 3 to 4 per cent., an immensely
greater proportion than occurs even in very badly ventilated rooms,
that marked discomfort, with dyspnoea, began to be felt. No close
odour could be detected.
Nevertheless, experience has shown that it is a good working rule for
ventilation to take the limit of permissible respiratory impurity at
2 parts of carbon dioxide per 10,000; and the 17 litres of carbon dioxide
given off in the hour will require 85,000 litres (or 3,000 cubic feet) of
air to dilute it to this extent. This is the average quantity required
for the male adult per hour. For men engaged in active labour, as in
factories or mines, twice this amount may not be too much. For
women and children less is required than for men. If a room smells
close, it needs ventilation, whatever be the proportion of carbon dioxide
in the air. It must be remembered that in permanently occupied
rooms mere increase in the size will not compensate for incomplete
renewal of the air, although it may be easier to ventilate a large room
than a small one without causing draughts and other inconveniences.
But as few apartments are occupied during the whole twenty-four hours,
a large room which can be thoroughly ventilated in the absence of its
inmates has a distinct advantage over a small one in its great initial
stock of fresh air. The cubic space per head in an ordinary dwelling-
house should be not less than 28 cubic metres or 1,000 cubic feet.
The quantity of carbon dioxide given off (and of oxygen consumed)
is not only affected by muscular work, but also by everything which
influences the general metabolism. In males it is greater on the
average than in females (in the latter there is a temporary increase
during pregnancy), but for the same body- weight and under similar
external conditions there is no difference between the sexes. The
gaseous exchange is greater in proportion to the body-weight in the
child than in the adult. This depends largely on the fact that,
other things being equal, the metabolism is relatively to the body-
weight more active in a small than in a large organism, since
the surface (and therefore the heat loss) is relatively greater in the
former. But it has been shown that even in proportion to the
surface the metabolism is greater in youth than in adult life, and
greater in the vigorous adult than in the old man. So that the age
of the organism has an influence apart from the extent of surface.
The taking of food increases the gaseous exchange, partly from the
244
RESPIRATION
increased mechanical and chemical work performed by the ali-
mentary canal and the digestive glands. But that this is not the
sole cause of the increase is shown by the fact that it varies with
different kinds of food to a greater extent than can be explained
by differences in the ease with which they are digested. For in-
stance, maize produces a much greater increase than oats when
given in equal amount, and a protein diet a greater increase than a
diet of carbo-hydrate or fat. Sleep diminishes the production of
carbon dioxide partly because the muscles are at rest, but also to
some extent because the external stimuli that in waking life excite
the nerves of special sense are absent or ineffective. Even a bright
light is said to cause an increase in the atmount of carbon dioxide
produced and of oxygen consumed ; but probably only by increasing
muscular movements, including the movements of respiration.
The external temperature also has an influence. In poikilothermal
animals (such as the frog), the temperature of which varies with
that of the surrounding medium, the production of carbon dioxide,
on the whole, diminishes as the external temperature falls, and
increases as it rises. In homoiothermal animals, that is, animals
with constant blood temperature, external cold increases the pro-
duction of carbon dioxide and the consumption of oxygen. But if
the connection of the nervous system with the striated muscles has
been cut out by curara, the warm-blooded animal behaves like the
cold-blooded (Pfliiger and his pupils in guinea-pig and rabbit).
These interesting facts will be returned to under ' Animal Heat.'
Cold-blooded animals produce far less carbon dioxide, and con-
sume far less oxygen, per kilo of body-weight than warm-blooded.
The following table shows the relation between the body-weight
and the excretion of carbon dioxide in man :
Age.
Weight in Kilos.
COj excreted per Kilo
per Hour.
r.58
84-6
0-41 gramme
44
76-5
0-48
Male 35
6o5
82
0-51
0-49
16
57'7
o-59
I 9'6
22
0-92
C66
66-9
o-39
Female j 3°
53-9
55'7
o-54
o-45
Uo
23
0-83
The next table illustrates the difference in the intensity of metab-
olism in different kinds of animals, a difference, however, largely
dependent upon relative size:
THE CHEMISTRY OF EXTERNAL RESPIRATION
245
Oxygen absorbed per
Kilo per Hour.
Carbon Dioxide given off
per Kilo per Hour.
Respiratory Quotient
Animal.
CO2 Oo (in COa)
In Grms.
In C.C.
In Grms.
InCC.
02 °r 02
Greenfinch -
I3-000
9091
13-590
6909
0-76
Hen -
I-058
740
I-327
675
O-gi
Dog -
I-303
911
I-325
674
o-74
Rabbit
0-987
690
1-244
632
0-91
Sheep -
0-490
343
0-671
341
0-99
Boar -
0-3QI
273
0-443
225
0-82
Frog -
O'IO5
73'4
0-113
577
0-78
Crayfish
0-054
38
0-064
32-7
0-86
Forced respiration, although it will temporarily increase the
quantity of carbon dioxide given off by the lungs, and thus raise
for a short time the respiratory quotient, does not sensibly affect
the production; it is only the store of already formed carbon dioxide
in the body which is drawn upon. The amount of oxygen taken
up is little altered by changes in the movements of respiration.
Within wide limits the oxygen consumption of the organism is in-
dependent of the supply of oxygen offered to it.
How it is that the depth of the respiration may affect the rate at
which carbon dioxide is eliminated, we can only understand when
we have examined the process by which the gaseous interchange
between the blood and the air of the alveoli is accomplished; and
before doing this it is necessary to consider the condition of the
oxygen and carbon dioxide in the blood.
SECTION IV. — THE GASES OF THE BLOOD.
Physical Introduction. — Matter may be assumed to be made up of
molecules beyond which it cannot be divided without altering its essen-
tial character. A molecule may consist of two or more particles of
matter (atoms) bound to each other by chemical links. The kinetic
theory of matter supposes the molecules of a substance to be in constant
motion, frequently colliding with each other, and thus having the direc-
tion of their motion changed.
In a gas the mean free path, that is, the average distance which a
molecule travels without striking another, is comparatively long, and
far more time is passed by any molecule without an encounter than is
taken up with collisions. Although the average velocity of the mole-
cules is very great, these collisions will produce all sorts of differences
in the actual velocity of different molecules at any given time. Some
will be moving at a greater, some at a slower rate, than the average;
while some may be for a moment at rest. If the gas is in a closed
vessel, the molecules will be constantly striking its sides and rebounding
from them. If a very small opening is made in the vessel, some mole-
cules will occasionally hit on the opening and escape altogether. If the
opening is made larger, or the experiment continued for a longer time
24« RESPIRA TION
with the small opening, all the molecules will in course of time have
passed out of the vessel into the air, while molecules of the oxygen,
nitrogen, and argon of the air will have passed in. In a gas, then, not
enclosed by impenetrable boundaries, there is no restriction on the path
which a molecule may take, no tendency for it to keep within any limits.
When two chemically indifferent gases are placed in contact with each
other, diffusion will go on till they are uniformly mixed. The diffusion
of gases may be illustrated thus. Suppose we have a perfectly level
and in every way uniform field divided into two equal parts by a visible
but intangible line, the well-known whitewash line, for instance. On
one side of the line place 500 blind men in green, and on the other 500
blind men in red. At a given signal let them begin to move about in
the field. Some of the men in green will pass over the line to the ' red '
side; some of the men in red will wander to the ' green ' side. Some
of the men may pass over the line and again come back to the side
they started from. But, upon the whole, after a given interval has
elapsed, as many green coats will be seen on the red side as red coats
on the green. And if the interval is long enough there will be at length
about 250 men in red and 250 in green on each side of the boundary-
line. When this state of equilibrium has once been reached, it will
henceforth be maintained, for, upon the whole, as many red uniforms
will pass across the line in one direction, as will recross it in the other.
In a liquid it is very different; the molecule has no free path. In the
depth of the liquid no molecule ever gets out of the reach of other
molecules, although after an encounter there is no tendency to return on
the old path rather than to choose any other; so that any molecule
may wander through the whole liquid. Although the average velocity
of the molecules is much less in the liquid state than it would be for
the same substance in the state of gas or vapour (gas in presence of its
liquid), some of them may have velocities much above the average.
If any of these happen to be moving near the surface and towards it,
they may overcome the attraction of the neighbouring molecules and
escape as vapour. But if in their further wanderings they strike the
liquid again, they may again become bound down as liquid molecules.
And so a constant interchange may take place between a liquid and its
vapour, or between a liquid and any other gas, until the state of equi-
librium is reached, in which on the average as many molecules leave the
liquid to become vapour as are restored by the vapour to the liquid, or as
many molecules of the dissolved gas escape from solution as enter into it.
For the sake of a simple illustration, let us take the case of a shallow
vessel of water originally gas-free, standing exposed to the air. It will
be found after a time that the water contains the atmospheric gases in
certain proportions — in round numbers, about Tfoj of its volume of
oxygen and £G of its volume of nitrogen (measured at 760 mm. mercury
and o° C.).
Now, let a similar vessel of gas-free water be placed in a large airtight
box filled with air at atmospheric pressure, and let the oxygen be all
absorbed before the water is exposed to the atmosphere of the box.
The latter now consists practically only of the nitrogen of the air, and
its pressure will be only about four-fifths that of the external atmo-
sphere. Nevertheless, the quantity of nitrogen absorbed by the water
will be exactly the same as was absorbed from the air. If the box
was completely exhausted, and then a quantity of oxygen, equal to that
in it at first, introduced before the water was exposed to it, the pressure
would be found to be only about one-fifth that of the external atmo-
sphere; but the quantity of oxygen taken up by the water would be
exactly equal to that taken up in the first experiment.
THE GASES OF THE PJ.OOD
*\\
Two well-loiown physical laws are illustrated by our supposed ex-
periments: (i) In a mixture of gases which do not act chemically on each
other the pressure exerted, by each gas (called the partial pressure of the
gas) is the same as it ivould exert if the others were absent. (2) The quan-
tity (mass) of a gas absorbed by a liquid which does not act chemically upon
it is proportional to the partial pressure of the gas. It also depends upon
the nature of the gas and of the liquid, and on the temperature, increase
of temperature in general diminishing the quantity of gas absorbed.
It is to be noted that when the volume of the absorbed gas is measured
at a pressure equal to the partial pressure under which ic was absorbed,
the same volume of gas is taken up at every pressure.
The volume of a gas (reduced to o° C. and 760 mm. pressure) physi-
cally absorbed or dissolved in i c.c. of a liquid exposed to the gas at
760 mm. pressure is called the absorption coefficient of the gas in that
liquid. The following table from Bohr shows the absorption coefficients
of the three gases of physiological interest — oxygen, nitrogen, and
carbon dioxide in water, blood-plasma, whole blood and blood-corpuscles
at the body temperature (38° C.) :
Oxygen.
Nitrogen.
Carbon Dioxide.
Water
0-0237
O-OI22
o'555
Blood-plasma
0'023
O-OI2
0-541
Blood - ---
O-O22
O-OII
0-511
Blood-cells -
0-019
o-oio
0-450
Suppose, now, that a vessel of water, saturated with oxygen and
nitrogen for the partial pressures under which these gases exist in the
air, is placed in a box filled with pure nitrogen at full atmospheric pres-
sure. As we have seen, there is a constant interchange going on between
a liquid which contains gas in solution and the atmosphere to which it
is exposed. Oxygen and nitrogen molecules will therefore continue to
leave the water; but if the box is large, few oxygen molecules will find
their way back to the water, and ultimately little oxygen will remain
in it. In other words, the quantity of oxygen absorbed by the water
will become again proportional to the partial pressure of oxygen, which
is not now much above zero. On the other hand, molecules of nitrogen
will at first enter the water in larger number than they escape from it,
for the pressure of the nitrogen is now that of the external atmosphere,
of which its partial pressure was formerly only four-fifths. In unit
volume of the gas above the water there will be 5 molecules of nitrogen
for every 4 molecules in the same volume of atmospheric air. There-
fore, on the average 5 nitrogen molecules will in a given time get en-
tangled by liquid molecules for every 4 which came within their sphere
of attraction before. On the whole, then, the water will lose oxygen
and gain nitrogen, while the atmosphere of the airtight box will gain
oxygen and lose nitrogen.
In the case of water, in which oxygen and nitrogen are absorbed
solely in solution, the partial pressures of these gases under which the
water was originally saturated could, of course, be easily" calculated
from the amount dissolved and the ccefficient of absorption. But
supposing that these partial pressures were unknown, it is evident that
by exposing it to an atmosphere of known composition, and afterwards
determining the changes produced m the composition of that atrnp'
248
RESPIRATION
feFQ
•G
sphere by loss to, or gain from, the gases of the water, we could find out
something about the original partial pressures. If, for example, the
quantity of oxygen in the atmosphere or the
chamber was increased, we could conclude that
the partial pressure of oxygen under which the
wattr had been saturated was greater than
that in the chamber at the beginning of the
experiment. And if we found that with a
certain partial pressure of oxygen in the atmo-
sphere of the chamber there was neither gain
nor loss of this gas, we might be sure that the
partial pressure (the temperature being sup-
posed not to vary), was the same when the
water was saturated. We shall see later on
how this principle has been applied to deter-
mine the partial pressure of oxygen or carbon
dioxide which just suffices to prevent blood, or
any other of the liquids of the body, from
losing or gaining these gases when they are not
merely dissolved, but also combined in the
form of dissociable compounds. This pressure
is evidently equal to that exerted by the gases
of the liquid at its surface, which is sometimes
called their ' tension ' ; for if it were greater,
gas would, upon the whole, pass into the blood ;
and if it were less, gas would escape from the
blood. Thus, the tension of a gas in solution in
a liquid is equal to the partial pressure of that
gas in an atmosphere to which the liquid is ex-
posed, which is just sufficient to prevent gain or
loss of the gas by the liquid (p. 258).
The following imaginary experiment may
further illustrate the meaning of the term ' ten-
sion ' of a gas in a liquid in this connection.
Suppose a cylinder filled with a liquid con-
taining a gas in solution, and closed above by
a piston moving airtight and without friction,
in contact with the surface of the liquid (Fig.
117). Let the weight of the piston be balanced
by a counterpoise. The pressure at the sur-
face of the liquid is evidently that of the
atmosphere. Now; let the whole be put into
the receiver of an air-pump, and the air
gradually exhausted. Let exhaustion proceed
until gas begins to escape from the liquid and
lies in a thin layer between its surface and the
piston, the quantity of gas which has become
free being very small in proportion to that
still in solution. At this point the piston is
acted upon by two forces which balance each
other, the pressure of the air hi the receiver
acting downwards, and the pressure of the gas
escaping from the liquid acting upwards. If
the pressure in the receiver is now slightly
increased, the gas is again absorbed. The pressure at which this just
happens, and against which the piston is still supported by the impacts
of gaseous molecules flying out of the liquid while no pressure is as yet
Fig. 117. — Imaginary Ex-
periment to illustrate
' Tension ' of a Gas in a
Liquid. P, frictionless
piston; L, liquid in cy-
linder; G, gas beginning
to escape from liquid.
P is exactly counter-
poised. In addition to
the manner described in
the text, the experiment
may be supposed to be
performed thus: Let the
weight, W, be deter-
mined which, when the
receiver is completely
exhausted, suffices just to
keep the pir :on in contact
with the liquid. The
pressure of the gas is
then just counter-
balanced by W; and if
S is the area of the cross-
section of the piston, the
pressure of the gas per
W
unit of area is ^-. Or, if
o
the piston is hollow, and
mercury is poured into
it so as just to keep it in
contact with the liquid,
the height of the column
of mercury required is
also equal to the pressur e
or tension of the gas.
THE GASES OF THE BLOOD
249
exerted directly between the liquid and the piston, is obviously equal
to the pressure or tension of the gas in the liquid.
From the above principles it follows that a gas held in solution may
be extracted by exposure to an atmosphere in which the partial pressure
of the gas is made as small as possible. Thus, oxygen can be obtained
from liquids in which it is simply dissolved by putting them in an
atmosphere of hydrogen or nitrogen, in which the partial pressure of
oxygen is zero, or in the vacuum of an air-pump, in which it is extremely
small. Heat also aids the expulsion of dissolved gases. Some gases
held in weak chemical union, like the loosely-combined oxygen of
oxyhaemoglobin, can be obtained by dissociation of their compounds
Fig. 1 1 8.- — Scheme of Gas-Pump. A, the blood
bulb; B, the froth chamber; C, the drying tube;
D, fixed mercury bulb ; E, movable mercury
bulb connected by a flexible tube with D; F,
eudiometer; G, a narrow delivery tube; i, 2, 3, 4,
taps, 4 being a three-way tap. A is filled with
blood by connecting the tap i by means of a
tube with a bloodvessel. Taps i and 2 are then
closed. The rest of the apparatus from B to D is
now exhausted by raising E, with tap 4 turned
so as to- place D only in communication with G,
till the mercury fills D. Tap 4 is now turned so as
to connect C with D, and cut off G from D, and E
is lowered. The mercury passes out of D, and air
passes into it from B and C. Tap 4 is again turned
so as to cut off C from D and connect G and D. E
is raised and the mercury passes into D and forces
the air out through G, the end of which has not
hitherto been placed under F. This alternate
raising and lowering of E is continued till a man-
ometer connected between C and 4 indicates that
the pressure has been sufficiently reduced. The
tap 2 is now opened ; the gases of the blood bubble up into the froth chamber, pass
through the drying-tube C, which is filled with pumice-stone and sulphuric acid, and
enter D. The end of G is placed under the eudiometer F, and by raising E, with
tap 4 turned so as to cut off C, the gases are forced out through G and collected
in F. The movements required for exhaustion can be repeated several times till
no more gas comes off. The escape of gas from the blood is facilitated by immersing
the bulb A in water at 40° to 50° C.
when the partial pressure is reduced. More stable combinations may
require to be broken up by chemical agents — carbonates, for instance,
by acids.
Extraction of the Blood-Gases. — This is best accomplished by ex-
posing blood to a nearly perfect vacuum. The gas-pumps which have
been most largely used in blood analysis are constructed on the principle
of the Torricellian vacuum. A diagram of a simple form of Pfliiger's
gas-pump is given in Fig. 118. The gases obtained are ultimately dried
and collected in a eudiometer, which is a graduated glass tube with its
mouth dipping into mercury. The carbon dioxide is estimated by
introducing a little potassium hydroxide to absorb it. The diminution
in the volume of the gas contained in the eudiometer gives the volume
of the carbon dioxide. The oxygen may be estimated by putting into
the eudiometer more than enough hydrogen to unite with all the oxygen
so as to form water, and then, after reading off the volume, exploding
the mixture by means of an electric spark passed through two platinum
wires fused into the glass. One-third of the diminution of volume
represents the quantity of oxygen present. It can also be estimated
250 RESPIRATION
by absorption with a solution of pj-rogallic acid and potassium hydrox-
ide, or an alkaline solution of sodium hydrosulphite, which is more
cleanly. The remainder of the original mixture of blood-gases, after
deduction of the carbon dioxide and oxygen, is put down as nitrogen
(with, no doubt, a small proportion of argon). For the sake of easy
comparison, the observed volume of gas is always stated in terms of its
equivalent at a standard pressure and temperature (760 mm., or some-
times on the Continent i metre of mercury, and o° C.).
It is also possible in various ways to estimate the amount of oxygen
in blood without the use of the pump. Thus, since a definite volume of
oxygen (i -338 c.c. at o° C. and 760 mm. pressure) combines with it
gramme of haemoglobin, we can calculate the total volume of oxygen
present if we know how much of the blood-pigment is in the form of
oxyhaemoglobin ; and this can be determined by means of the spectro-
photometer. Or potassium ferricyanide may be added to the blood.
This expels the oxygen from its combination with the haemoglobin,
which then unites with an exactly equal amount of oxygen obtained
from the ferricyanide to form methaemoglobin (Haldane) (p. 75).
In the hands of Barcroft and his pupils this method has been highly
developed, so that accurate results can be obtained with small quantities
of blood (i c.c., and with the smaller apparatus even o-i c.c.). Bar-
croft's differential apparatus consists essentially of two small bottles,
as nearly alike as possible, connected by a manometer filled with oil (of
cloves). The amount of oxygen liberated in one of the bottles by
potassium ferricyanide from a measured amount of blood can be esti-
mated from the displacement of the liquid in the manometer. The
function of the second bottle is to automatically eliminate effects due
to changes in the temperature of the bath in which the apparatus is
immersed, etc., since both bottles are affected alike.
The Quantity of the Blood-Gases.— In arterial and in venous blood
oxygen, carbon dioxide, nitrogen, and argon are constantly found.
Both the oxygen and the carbon dioxide vary considerably in
amount in the arterial blood, even of individuals of the same animal
group, and, of course, much more in the venous blood, as might
naturally be expected, since even to the eye it varies greatly accord-
ing to the vein it is obtained from, the rapidity of the circulation,
and the activity of the tissues which it has just left. In one
observation on blood obtained directly from a human artery, 2i«6c.c.
of oxygen, 40*3 c.c. of carbon dioxide, and 1-6 c.c. of nitrogen were
found in 100 c.c. of blood. The quantity of oxygen taken up outside
of the body by specimens of human blood drawn from six normal
persons, when shaken up with atmospheric air, varied from 17-6 c.c.
to 22-5 c.c. per 100 c.c. of blood, the variations depending mainly
on the haemoglobin content. The arterial blood as it actually left
the lungs of those persons must have contained somewhat less oxygen
(about i c.c. less per looc.c. of blood), since the partial pressure of
oxygen in the alveolar air is decidedly below that in atmospheric
air. In dogs the amount of carbon dioxide in arterial blood has
been found to vary from 35 to 45 c.c. per 100 c.c. of blood, the
differences being due to variations in the extent of the pulmonary
ventilation and to other factors.
THE GASES OF THE BLOOD 251
In a series of observations on the venous blood of dogs the oxygen
content ranged from 5-5 to 16-6 c.c. (average 11-9 c.c.), and the carbon
dioxide content from 38-8 c.c. to 47-5 (average 44-3 c.c.) per 100 c.c.
of blood (Schoffer) . It will be sufficiently accurate to assume that
on the average,
Volumes of
67 C02. N£
100 volumes of arterial blood yield 20 40 1-2
,, ,, mixed venous blood (from
right heart) yield - 10-12 45-50 1-2
(reduced to o° C. and 760 mm. of mercury).
Average venous blood contains 7 or 8 per cent, by volume less
oxygen, and 7 or 8 per cent, more carbon dioxide, than arterial
blood. Thus, in the lungs the blood gains about twice as many
volumes of oxygen per cent, as the air loses, and the air gains about
half as many volumes of carbon dioxide per cent, as the blood loses.
It is easy to see that this must be so, for the volume of air inspired
in a given time is about twice as great as that of the blood which
passes through the pulmonary circulation (pp. 223, 236). Even
arterial blood is not quite saturated with oxygen; it can still take
up a variable small amount. The percentage saturation with
oxygen of the arterial blood of a normal woman from whom
blood was being transfused into a patient was directly determined.
The blood proved to be 94 per cent, saturated — i.e., it could stili
have taken up about one-sixteenth of the quantity contained in
it. Nor is venous blood nearly saturated with carbon dioxide;
when shaken with the gas it can take up about 150 volumes per cent.
The total oxygen capacity of the blood in any individual can be
determined, if the volume of the blood is known (p. 56), by estimating
the amount of oxygen needed to saturate a sample of the blood.
This is most conveniently done by the ferricyanide method with
Barcroft's apparatus. Suppose, for example, that i c.c. of blood,
after being thoroughly shaken up with air or oxygen, gives off
0-2 c.c. of oxygen when acted upon by ferricyanide, and that the
total volume of the blood has been determined to be 5 litres, then
the total oxygen capacity of the blood will be 1,000 c.c. This
quantity, it is clear, is a measure of the power of the blood to trans-
port oxygen. The oxygen capacity of a sample of blood is propor-
tional to the amount of hemoglobin in it, so that the estimation of
the percentage amount of haemoglobin by a properly standardized
haemoglobinometer is really an estimation of the oxgyen capacity of
the quantity of blood used for the determination. The total oxygen
capacity of the body cannot, of course, be derived from such an
observation, any more than the total quantity of haemoglobin, unless
the amount of blood in the body is known.
When the gases are not removed from blood immediately after
252 RESPIRATION
it is drawn, it yields more carbon dioxide and less oxygen than if it
is evacuated at once (Pfliiger). From this it is concluded that
oxidation goes on in the blood for some time after it is shed. The
oxidizable substances are, however, confined to the corpuscles,
which suggests that ordinary metabolism simply continues for
some time in the formed elements of the shed blood, and that the
disappearance of oxygen is not due to the oxidation of substances
which have reached the blood from the tissues. It is an interesting
fact that the rate of oxygen consumption of nucleated (bird's) erv-
throcytes is much greater than that of non-nucleated mammalian
corpuscles. The young non-nucleated erythrocytes, which in experi-
mental anaemia in mammals (e.g., after haemorrhage) find their way
in large numbers into the circulation, have a relatively intense
metabolism, and therefore consume a relatively large amount of
oxygen.
The Distribution and Condition of the Oxygen in the Blood. — The
oxygen is nearly all contained in the corpuscles. A little oxygen
can be pumped out of serum (0-2 or 0-3 per cent, by volume), but this
follows the Henry-Dalton law of pressures — that is, it comes off in
proportion to the reduction of the partial pressure of the oxygen in
the pump, and is simply in solution.
When blood at body temperature is shaken up with air at the
ordinary pressure, corresponding to a partial pressure of oxygen
of a little over one-fifth of an atmosphere (in round numbers 160 mm.
of mercury), the blood-pigment becomes saturated with oxygen or
nearly so. When the blood is now pumped out, very little oxygen
comes off till the pressure has been reduced to about half an atmo-
sphere, corresponding to a pressure of oxygen of about 80 mm.
At about 70 mm. partial pressure the dissociation is somewhat
greater. At a third to a quarter of an atmosphere (50 to 40 mm.;
the amount of oxygen liberated is markedly increased, and the dis
sociation becomes more and more rapid as the pressure falls to-
wards zero. This behaviour shows that the oxygen is not simply
absorbed, but is united, as a dissociable compound, to some con-
stituent of the blood. The same thing is, of course, seen when
defibrinated blood is saturated at body temperature with oxygen at
different pressures. As the partial pressure of the gas is increased
from zero the first increments of pressure correspond to a much
greater absorption of oxygen than further equal increments. Thus
as is seen in Fig. 120, with an oxygen pressure of 10 mm. 100 c.c.
of blood took up 6 c.c. of oxygen, or 30 per cent, of the amount
required to saturate it. When the pressure of oxygen was 30 mm.
over 16 c.c. of oxygen was absorbed, the blood being 80 per cent,
saturated. A further increase of the oxygen pressure to 40 mm.
increased the quantity of the gas taken up by only 2 c.c. (to 90 per
cent, saturation). Ttu next increment of 10 mm. in the oxygen
THE GASES OF THE BLOOD
253
385
7
pressure only produced an additional absorption of I c.c., and above
this increasing the pressure had very little effect.
We may suppose that at the ordinary temperature and pressure
some oxygen is continually escaping from the bonds by which it is tied
to the haemoglobin; but, on the whole, an equal number of free mole-
cules of oxygen, coming within the range of the haemoglobin molecules,
are entangled by them, and thus equilibrium is kept up. If now the
atmospheric pressure, and therefore the partial pressure of oxygen
is reduced, the tendency
of the oxygen to break ne»-ce"tage of OxvQC'> >s>.
off from the haemoglobin
will be unchanged, and as
many molecules on the
whole will escape as before ;
but even after a consider-
able reduction of pressure
the haemoglobin, such is its
avidity for oxygen, will still
be able to seize as much
oxygen as it loses. The
more, however, the partial
pressure of the oxygen is
diminished — that is to say,
the fewer oxygen molecules
there are in a given space
above the haemoglobin—
the smaller will be the
chance of the loss being
made up by accidental cap-
tures. At a certain pressure
the escapes will become
conspicuously more numer-
ous than the captures ; and
the gas-pump will give evi-
dence of this. The higher
the temperature of the
haemoglobin is, the greater
will be the average velocity
of the molecules, and the
Fig. 119. — Curves of Dissociation of Oxyhaemo-
globin freed from salts by dialysis (after Bar-
croft). Along the horizontal axis are plotted
the partial pressures (numbers below the curve)
of oxygen in air, to which a solution of haemo-
globin was exposed. The corresponding per-
centages of oxygen are given above the curve.
Along the vertical axis is plotted the percentage
saturation of the haemoglobin with oxygen.
greater the chance of escape of molecules of oxygen.
It is easily proved that the substance in the corpuscles which
unites with oxygen is the blood-pigment. Although a solution of
oxyhaemoglobin crystals behaves towards oxygen somewhat differ-
ently from blood containing the same proportion of the native pig-
ment, the maximum amount of oxygen taken up is the same for
each. Much labour has been spent in determining curves which
express the relation between the partial pressure of oxygen to which
blood or a haemoglobin solution is exposed, and the proportion to,
which the blood pigment becomes saturated with oxygen under
each pressure. The differences in the results of the various in-
vestigators who have worked out the curves of dissociation for
haemoglobin and for blood (Figs. 119, 120, 121) have been largely
cleared up by the researches of Barcroft and his co-workers. One
254
RESPIRATION
factor which was overlooked in the earlier observations is the
influence of salts.
The form of curve (a rectangular hyperbola, Fig. 119) which Hiifner
put forward by an unjustifiable generalization, as the curve of dis-
sociation of oxyhaemoglobin is only found when the haemoglobin solu-
tion is thoroughly freed from salts, as by prolonged dialysis. When
this condition is fulfilled it can be shown that the curve is always a
rectangular hyperbola, but a different one for each temperature at
which the observations are made. For haemoglobin solutions not freed
from salts or for blood or dilutions Of blood the curve is of a different
order altogether, a curve with a double contour (S-shaped). (Figs. 120,
121). If to a solution of haemoglobin freed from salts and yielding a
rectangular hyperbola as its dissociation curve, salts be added in the
quantities and of the kind known to exist in dog's blood, the curve of
no
7
is &a
16 ec
14 cc
1 2 co
IOC&
see.
6 C.C
4CC.
2 C.C.
03C.C,
0 10 to 30 40 10 M 70 80 00 100 110 120 130 140 ISO
Fig. 120. — Curves of Dissociation of Oxygen for Horse's Blood (B) and Dog's Hemo-
globin solution (H) at 38° C. (Bohr). The figures along the base-line are the
partial pressures of oxygen to which the bLood and haemoglobin solution were
exposed. Those along the vertical axis on the left are the percentage saturations
with oxygen. The figures along the vertical at the right give the actual number
of c.c. of oxygen chemically combined by 100 c.c. of the blood for each pressure
of oxygen. The interrupted line P indicates the amount of oxygen dissolved in
the plasma of the blood at each partial pressure on the assumption that the
plasma is two-thirds of the volume of the blood. Thus, at 150 mm. oxygen
pressure the plasma of 100 c.c. of blood took up 0-3 c.c. oxygen.
dissociation given by dog's blood is obtained. The addition of the
salts appropriate to human blood in the proper amounts causes the
hyperbolic curve of the pure haemoglobin solution to change into an
S-shaped curve, such as is given by human blood, and so on.
The foundation has thus been removed from the theory that
different animals possess haemoglobins differing in their capacity
to take up oxygen. The salts are supposed to alter the dissociation
curve, by changing the degree of aggregation of the haemoglobin
molecules- — i.e., by causing them to adhere to each other to a greater
or less extent according to the quantity and kind of salts present.
Another factor which greatly influences the binding power of
haemoglobin for oxygen, and therefore the dissociation curve, is
the reaction of the blood (p. 24). When the hydrogen-ion concen-
TtiE CASES OF THE BLOOD 255
tration is increased, as by addition of carbon dioxide (Fig. 121) or
lactic acid, the effect is to increase the dissociation tension of
o. \\-lKemoglobin, or what is a different way of expressing the same
thing, to diminish the amount of ox3
(42-5)
CO (^
[Wolffberg -
—
(26)
18-37
C J^ H
Nussbaum -
—
(27)
24-33
f«
Loewy and Schrotter ~\ ~
Haldane and Smith J man
(.200 +
—
(37'7)
34-59
(45)
It is chiefly the enormous differences in the recorded oxygen
tensions of the arterial blood which excite surprise. To some ex-
tent, indeed, these also may depend upon differences in the partial
pressure of the oxygen in the alveoli, and it has been shown experi-
mentally (by the aerotonometer) that with increasing oxygen tension
of the inspired air the oxygen tension of the arterial blood increases
(Fredericq). Still, the differences which can possibly have existed
in the partial pressure of the oxygen in the alveoli in the various
series of observations can only to a small extent account for the
differences in the results. The main reason for the great range of
values lies unquestionably in the different experimental procedures
* The numbers in brackets are averages.
262 RESPIRA TION
by which the)' were obtained. There is no doubt that in the earlier
observations with the aerotonometer (Strassburg) the oxygen of
the blood could not have come into equilibrium with the mixture
in the gas space, in which the oxygen pressure was at the beginning
much lower than that in the blood; the results are therefore too low.
The same is true for the oxygen tension of the venous blood, but as
this is in any case considerably smaller than that of the arterial
blood, the proportional error is not so great. The later experiments
(of Herter), given in the second line of the table, yield much higher
values, owing to improved technique, but the findings are still to be
regarded as minimal and not average results. At the other end of
the scale stand the results of Haldane and Smith, who found in man
an oxygen tension in the arterial blood of over 200 mm. of mercury
equal to more than 26 per cent, of an atmosphere. This exceeds
the partial pressure of oxygen in the external air, and is about twice
as great as that of the air of the alveoli. In the bird they found
an oxygen tensien of between 300 and 400 mm., equal to 45 per
cent, of an atmosphere.
The chief interest of this discussion of the blood-gas tensions lies
in their fundamental importance in the problem of the gaseous
exchange in the lungs, on the one hand, and between the blood and
tissues on the other. In the presence of such results Haldane and
Smith necessarily adopted a secretion theory of gaseous exchange
in the lungs. For it was manifestly impossible for oxygen to diffuse
from the alveoli into the blood against the slope of pressure.
Their findings, however, differed so vastly from those of all observers
who had used tonometric methods, and it seemed so difficult to assign
an adequate physiological value to the slight increase in the percentage
saturation of the haemoglobin with oxygen (see Figs. 119-121), which
could be brought about by even a great excess of oxygen tension above
that of atmospheric air, that there was a general disposition to distrust
the accuracy of their method. At the same time the ordinary tono-
metric technique left so much to be desired that there seemed little
hope of bringing the matter to a decisive test. The introduction a
few years ago by Krogh, of better aerotonometric methods, and the
remarkable series of researches carried out by their aid, have changed
the whole aspect of the question. He showed that in the arterial blood
of rabbits the oxygen tension was in all cases somewhat (usually 2 to
3 per cent, of the atmospheric pressure, or 15 to 23 mm. of mercury)
lower than the oxygen tension in air from the bifurcation of the trachea.
In animals it is not possible to obtain the actual alveolar air. These
results agree very well with those of Fredericq, who found in dogs
oxygen tensions of 13 to 14 per cent, of an atmosphere — i.e., something
like 100 mm. of mercury, when the animals breathed atmospheric air.
Krogh proved that the amount of oxygen lost by self-reduction of
the blood (see p. 261) in his aerotonometer was negligible, even in
rabbits, although it is known that rabbit's blood uses up more oxygen
than that of higher mammals. He also pointed our some sources of
error in the Haldane-Smith method. About the same time Haldane,
after a careful re-examination of the question, came to the con-
clusion that his previous results were much too high; and that
THE GASES OF THE BLOOD 263
during rest and when normal air is breathed the oxygen tension in
arterial blood never exceeds the tension in the alveolar air. He still
believes, and brings forward evidence for his belief, that even the best
aerotonometric methods yield with arterial blood oxygen pressures
lower than the true oxygen pressure in the blood leaving trie pulmonary
capillaries. But he no longer doubts that a sufficient slope of pressure
exists between the alveoli and the blood to explain the absorption of
oxygen under ordinary conditions.
To all intents and purposes, then, we may look upon the contro-
versy as closed, and with the happy result, too rare in physiological
disputes, that a practically unanimous conclusion has been arrived
at. While the oxygen tension in arterial blood may fall only slightly
below that in alveolar air, the difference perhaps being even less than
that found by Krogh, the slope of pressure is always, under ordinary
conditions at least, from the alveoli to the blood.
Mechanism of the Gaseous Exchange in the Lungs. — Granting
that this is so, it must still be asked whether the diffusion of oxygen
from the lungs into the blood can take place rapidly enough to
account for the quantities actually absorbed.
Calculations made on the basis of such anatomical and physical data
as are available (total surface of the lungs, thickness of the membrane
which separates the air of the alveoli and the blood in the capillaries,
rate of ' invasion,' or entrance of the gases into water; velocity of
diffusion of oxygen and carbon dioxide), indicate that even with differ-
ences of oxygen tension between the blood and the alveolar air, which
would lie within the limits of error of our present methods of measure-
ment, enough oxygen could diffuse across the pulmonary membrane to
cover the whole normal intake.
For example, it has been shown from determinations of the ' invasion-
coefficient ' of oxygen that 300 c.c. of oxygen, the amount ordinarily
absorbed in a minute, in an average man, can be carried from the alveo-
lar air into the wet surface of the pulmonary epithelium with a difference
of oxygen pressure of a little over 3 mm. of mercury. If during mus-
cular exercise six or seven times as much oxygen were absorbed, the
necessary difference of oxygen pressure would still be only about 20 mm.
of mercury, less than 3 per cent, of an atmosphere.
It is one thing, however, to know that the necessary oxygen can be
taken up into the surface of the pulmonary membrane by a purely
physical process, but quite another to prove that it can also be trans-
ported with sufficient speed across the thickness of the alveolar wall
into the blood. A direct test of this question, made by Krogh, has
also yielded an affirmative answer. He determined the amount of
carbon monoxide actually taken up in a given time in a human subject.
It was about 20 c c. per mm. of partial pressure in. the alveolar air per
minute when the subject was at rest, and a little above 30 c.c. when
breathing was forced, as it would be during heavy work. Now the
speed of diffusion of oxygen is somewhat greater than that of carbon
monoxide, so that at rest the subject could have absorbed between
200 and 300 c.c. of oxygen per minute with a difference _of oxygen
tension of only 10 mm. of mercury between the alveolar air and the
arterial blood. Even during hard muscular work the observed differ-
ences of oxygen tension seem adequate to the transport of the necessary
amount of oxygen.
264 RESPIRATION
So far, then, as the absorption of oxygen is concerned, there is every
reason to conclude that it is managed by physical processes alone.
Haldane, it is true, still contends that under exceptional conditions
when the call for oxygen is much increased, as during active mus-
cular exercise, or when an adequate intake is hampered by reduced
atmospheric pressure, as at high altitudes, the oxygen tension in
the arterial blood may materially exceed that in the alveolar air.
Those who have worked with other methods do not, however, grant
that even under these conditions there is any excess of oxygen
pressure in the blood. It may, of course, be formally admitted that
even if diffusion can account for the absorption of the whole of the
oxygen, this is not of itself a proof that it is by diffusion that the
thing is actually done ; it is only a reason for refusing to call in the
aid of a more recondite hypothesis, until the necessity for doing so
is clearly demonstrated.
As regards the carbon dioxide the evidence is fully as clear. The
speed of diffusion of carbon dioxide across such a membrane as the
alveolar wall being much greater than that of oxygen, still smaller
differences of tension would suffice to permit the whole normal out-
put of that gas to be eliminated by diffusion.
According to the observations of Bohr, nearly 500 c.c. of carbon
dioxide per minute could pass out of the blood by diffusion into the
alveolar air under a difference of partial pressure of i mm. of mercury.
This is with the ordinary breathing of a man at rest. With the in-
creased respiration associated with hard muscular work, this quantity
would be increased to between 700 and 800 c.c. The amount of carbon
dioxide eliminated during rest in an average adult (300 c.c.) can there-
fore be easily excreted by diffusion with a tension-difference of i mm.
of mercury. Even during very hard work the necessary tension differ-
ence need not be more than 3 mm. With a movement of carbon dioxide
so free as this, it is obvious that if the excretion of that gas is solely a
matter of diffusion its partial pressure in the arterial blood must be
nearly identical with its partial pressure in the alveolar air.
A glance at the table on p. 261 shows that while the carbon di-
oxide tension of venous blood may sometimes, perhaps generally,
exceed that of the alveolar air, the difference is quite small. The
average for the observations on man with the pulmonary catheter
was 45 mm., which compares with an average alveolar tension of
42 mm.
Experiments made by more modern methods have placed the
matter beyond doubt. Krogh proved, for example, that in rabbits
the carbon dioxide tension in the arterial blood was always slightly
(on the average 0-4 per cent, of an atmosphere, or 3 mm. of mercury)
higher than in air taken from the bifurcation of the trachea. Now
this air is known to contain slightly less carbon dioxide than the
alveolar air. Haldane 's results on the regulation of the respiration
(p. 281) would be unintelligible unless the carbon dioxide pressure
in the arterial blood adjusted itself with great rapidity, to changes
THE GASES OF THE BLOOD 265
in the tension of carbon dioxide in the alveolar air, so as always
to preserve a definite relation. It is quite generally assumed that
this relation is one of practical equality, and the classical method
of measuring the carbon dioxide tension in the arterial blood in man
is to determine it in the alveolar air.
Evidence in favour of the view that there is, besides diffusion,
an element of selective secretion in the exchange of gases through
the pulmonary membrane has been found by some writers in the
results of a study of the gases of the swim-bladder in fishes. This
study has demonstrated the existence of animal cells which actually
secrete gases. This fact, however, even if it removes a presump-
tion against, does not establish a presumption in favour of, the
secretion theory of external respiration. These gases consist of
oxygen, nitrogen, and usually a small quantity of carbon dioxide,
but in very different proportions from those in which they exist in
the air or the water. Thus, as much as 87 per cent, of oxygen has
been found in the bladder of fishes taken at a considerable depth,
but a smaller amount in those captured near the surface. When
the gas is withdrawn by puncturing the bladder with a trocar, the
organ rapidly refills, and the percentage of oxygen increases.
Further, this process of gaseous secretion is under the influence of
nerves, for gas ceases to accumulate in the organ when the branches
of the vagi that supply it are cut. In the tortoise stimulation of
the peripheral end of the vagus causes a fall of gaseous exchange
in the corresponding lung, with an accompanying rise in the other
lung. But this is a consequence of an alteration in the pulmonary
circulation through the vasomotor fibres for the lungs which are
known to run in the vagus in this animal. In the mammal, no such
effect has been demonstrated, and the decisive proof that the lungs
are gas-secreting glands which would be afforded by the discovery
of secretory nerves is wanting.
We have now completed the description of the phenomena of
external respiration, with the discussion of its central fact, the
exchange of gases between the blood and the air at the surface of
the lungs. It remains to trace the fate of the absorbed oxygen,
and to determine where and how the carbon dioxide arises.
SECTION V. — INTERNAL OR TISSUE RESPIRATION.
Seats of Oxidation. — The suggestion which lies nearest at hand
and which, as a matter of fact, was first put forward, is that the
oxygen does not leave the blood at all, but that it meets with
oxidizable substances in it, and unites with their carbon to form
carbon dioxide. While there is a certain amount of truth in this
view, oxygen, as already mentioned, being to some extent taken up
by freshly shed blood, and also by blood under other conditions,
to oxidize bodies, other than haemoglobin, either naturally contained
366 RESPIRATION
in it or artificially added, there is no doubt that the cells of the body
are the busiest seats of oxidation. This is shown by the presence
of carbon dioxide in large amount in lymph and other liquids which
are, or have been, in intimate relation with tissue elements ; by its
presence, also in considerable amount, in the tissues themselves —
in muscle, for instance ; by its continued and scarcely lessened pro-
duction not only in a frog whose blood has been replaced by physio-
logical salt solution, and which continues to live in an atmosphere
of pure oxygen, but in excised muscles ; and by the remarkable con-
nection between the amount of this production and the functional
state of those tissues. In insects the finest twigs of the tracheae,
through which oxygen passes to the tissues, actually end in the cells ;
and in luminous insects, like the glow-worm, it has been noticed
that the phosphorescence, which is certainly dependent on oxidation,
begins and is most brilliant in those parts of the cells of the light-
producing organ that surround the ends of the tracheae. Microscopic
evidence has been obtained that intracellular oxidation proceeds
most rapidly near surfaces like the nuclear and plasma membranes
— e.g., in the indophenol (p. 272) and similar reactions the coloured
oxidation products are deposited chiefly in and around the nuclei of
such cells as liver and kidney cells and frog's red corpuscles (Lillie).
The Passage of Oxygen from the Blood into the Tissues. — A
fundamental fact of tissue respiration is that the amount of oxygen
taken up by the cells depends essentially upon their needs, and not
upon the amount of oxygen offered to them in the blood. In every
case studied, an increase of functional activity on the part of an
organ leads to an increased call for oxygen by that organ, and an
increased consumption of oxygen in it. The cells cannot be cajoled,
so to say, into consuming more oxygen merely by increasing the
available supply. Nor can they be prevented from absorbing and
consuming more of whatever supply is available when they are
caused to work harder.
For skeletal muscle at rest, Barcroft gives 0-004 c.c. per gramme
per minute as the oxygen consumption; during maximal activity
twenty times as much (o«o8 gramme) . In the heart of a small dog
through which blood was pumped by a larger dog the oxygen intake
when the heart was beating feebly was, on the average, about
o-oi c.c. per gramme of heart-muscle per minute. When the heart
was caused to beat very strongly under the influence of adrenalin,
the oxygen intake rose in one case to 0-08, and in two others to 0-04.
In the resting pancreas the oxygen intake has been found to be 0-03
to 0*05 c.c. per gramme per minute; in the active pancreas, o-i c.c.
The corresponding number for the submaxillary gland at rest is
0-03, and in activity 0-09; for the kidney, 0-03 at rest or during
scanty secretion, and 0-07 or even 0-09 during active secretion; for
the liver in fasting animals o-oi, in fed animals 0-035.
INTERNAL OR TISSUE RESPIRATION 267
We are as yet less precisely informed as to the manner in which
the tissues regulate the amount of oxygen which they take up from
the blood, than in the case of the passage of oxygen into the blood
from the lungs. The problem, indeed, is superficially at least a
different and probably a more complex one. In the lungs the task
is to saturate, or nearly to saturate, the haemoglobin with oxygen,
whether the blood passes fast or slow. It is a monotonous invariable
process of 'oxygen-grabbing,' with no possibility of its ever being
overdone. In the tissues, the task is to meet the widely varying
demand from blood which is always charged with oxygen to ap-
proximately the same degree. How is this thing managed ? There
is little doubt that the process is again fundamentally a matter of
diffusion. The oxygen dissociated from the oxyhgemoglobin in the
capillaries must find its way through the plasma across the capillary
walls into the tissue lymph, and thence into the interior of the cells.
There is evidence that it can do so by physical diffusion. For the
oxygen tension in the capillary blood is in general higher than the
oxygen tension in the tissues. The common statement that the
partial pressure of oxjrgen in the tissues is zero, or nearly zero, fits
in very well with the conclusion that the oxygen is transported into
the cells from the blood of the capillaries by a process of diffusion.
For the slope of oxygen pressure thus maintained would ordinarily be
greater than in the lungs, since even at the end of the capillary tract
the venous blood still has a considerable partial pressure of oxygen.
The fact that such liquids as lymph, bile, urine, the serous fluids,
saliva, pancreatic juice and milk contain little or no oxygen was sup-
posed to support the view that the pressure of oxygen must be very low
in the tissues by which they are secreted, or with which they have been
in intimate contact. From isolated muscles no free oxygen at all can
be pumped out, and muscle being taken as a type of the other tissues
in regard to the problems of internal respiration, it was concluded that
the scarcity of oxygen in the parenchymatous liquids which bathe the
tissues deepens in the tissues themselves into actual famine. The
inference seemed plain. Either the tissues used up oxygen so rapidly
that with an average blood flow their wants could just be supplied,
or without actually consuming it they ' fixed ' and stowed it away in
some compound in which it was still available for oxidation in the meta-
bolic processes of the cell, but had lost the properties of free oxygen.
On the first alternative, an increased consumption of oxygen could only
be met by an increase in the blood flow; on the second assumption
the stored oxygen would supply the means of temporarily increasing
the metabolism even without an immediate augmentation of the blood
flow. Although it was recognized that even the resting metabolism
of certain organs was not inconsiderable, and required a good supply
of oxygen, it was always difficult to understand why inactive tissues
should have such an avidity for oxygen that practically every molecule
seemed to be captured as soon as it appeared. Nor did it help much to
assume that some of the tissue oxidation might really take place in
the tissue lymph, oxidizable products split off in the metabolism of
the cells passing out into the lymph before being burnt, and thus
diminishing the oxygen tension outside the capillary walls.
268 RESPIRATION
Recent work has indicated, however, that the oxygen pressure
in some tissues is far from negligible. In the resting submaxillary
gland, indeed, it seems to be practically equal to the oxygen pres-
sure in the venous blood leaving the organ (over 40 mm. of mercury
in certain experiments). In general, the same was found to be
the case for the kidney. This does not mean, of course, that in
such organs there is no slope of oxygen pressure from blood to
tissue, in virtue of which oxygen can be moved out of the blood
by diffusion. For at the beginning of the capillary tract the whole
difference in oxygen pressure between the arterial and the venous
blood would be available. At the end of the capillary tract, the
blood by the loss of oxygen to the tissues would have come approxi-
mately into equilibrium with them. These observations enable us
to understand better the manner in which the tissues themselves
can regulate their intake of oxygen. If the glands are using little
oxygen their oxygen tension will be relatively high, and the passage
of a comparatively small amount of oxygen from the blood in the
capillaries will suffice to bring it into equilibrium with the tissues,
after which the diffusion of oxygen will cease. If, on the other
hand, the consumption of oxygen in the glands is suddenly in-
creased, their oxygen pressure will fall, the pressure gradient be-
tween them and the blood will become steeper, and oxygen will
diffuse more rapidly into them from the capillaries. It must be
remarked, also, that up to a certain point the existence of a sub-
stantial oxygen pressure in the tissues permits them at once to
increase their intake of oxygen from the blood without the neces-
sity of an immediate increase in the blood flow. For, as the cells
consume the oxygen already present in and between them, the
tissue oxygen tension falls, and the gradient between the interior
and the exterior of the capillaries is thus rendered more abrupt.
These results were not obtained by direct tonometric measurement
of the oxygen pressure in the glands investigated, but were deduced
from observations on the quantities of oxygen taken up by them when
different oxygen pressures were produced in the capillaries by altering
the oxygen tension in the inspired air. The quantity of oxygen which
diffuses out of the capillaries in a given time will be proportional to
the difference of oxygen pressure on the two sides of the capillary wall.
If the pressure on the side of the tissues is always zero, then the quantity
of oxygen passing out will vary directly as the intracapillary oxygen
pressure. Far from doing this, the amount of oxygen taken up by the
glands was found to be about the same with intra-capillary oxygen
pressures as different as 61 mm. and 16 mm. of mercury. It should be
distinctly understood that no great importance must be attached to
the actual numbers in experiments of this kind. But the general con-
clusion that in some tissues, at any rate in the resting condition, a
sensible partial pressure of oxygen exists, seems to be established
(Yerzar). The application of the same method to muscle has led to
a different result. Here, the possible partial pressure of oxygen was
found decidedly less than that of the venous blood, although at times
a small oxygen pressure was detected in resting muscle (25 mm. or less)
269
Muscle may accordingly be taken as a type of tissues in which
the oxygen pressure is so low that the blood-flow through them
cannot be much diminished without interference with their absorp-
tion of oxygen, while in tissues like the resting submaxillary gland
a considerable diminution of the blood-flow can occur without
diminution of the oxygen consumption of the tissue. Whether
this difference is merely a quantitative one, depending upon the
great oxygen requirement of active muscle, or a qualitative difference
connected with the peculiar relations of oxygen to the muscular
contraction, is unknown. These relations have so great an interest
in connection with the problem of intracellular oxidation, and have
been so much more minutely studied than the relations of oxygen
to the functional work of other tissues, that a few words on the
respiration of muscle may fitly be introduced here. The subject
must be returned to later on (Chapters XII. and XIII.).
Fig. 123. — Fatigue of a Pair of Sartorius Muscles (Fletcher). A, in an atmosphere of
oxygen; B, in an atmosphere of nitrogen. A is partially restored by a rest of
five minutes.
Respiration of Muscle. — It is a remarkable fact that an excised
frog's muscle is capable of going on yielding carbon dioxide for a
long time, in the entire absence of oxygen, in a chamber, for instance,
filled with nitrogen or other indifferent gas. Not only so, but it
can be made to contract many times in this oxygen-free atmosphere,
although it loses its power of contraction sooner than in oxygen,
and does not show the same capacity for recuperation during an
interval of rest. In mammals the muscles can also be made to
contract repeatedly when the dissociable oxygen has, as far as pos-
sible, been got rid of from the blood by asphyxiating the animal, and
to give off a correspondingly large quantity of carbon dioxide,
although they lose their contractibility much more rapidly than the
muscles of the frog. This has usually been interpreted as meaning
that the carbon dioxide does not arise, so to speak, on the spot, from
*70 RESPIRATION
the immediate um'on of carbon and oxygen, but that a stock of
it is taken up by the muscle, and stored in some compound or
compounds, which are broken down during contraction, and more
slowly during rest, carbon dioxide in both cases being one of
the end-products. In a normal muscle with intact circulation,
while carbon dioxide is given off, certain of the other decomposition
products are supposed, in conjunction with oxygen and some sub-
stance rich in carbon, like sugar, to be regenerated into the material
which breaks down in contraction. When oxygen is not available,
as in an atmosphere of nitrogen, carbon dioxide is still given off, but
the other decomposition products are supposed not to be regenerated
to contractile substance, but to accumulate in the muscle, producing
the phenomena of fatigue, and eventually of rigor.
When muscle goes into rigor (Chapter XIII.) — and this is most
strikingly seen when the rigor is caused by raising the temperature
of frog's muscle to about 40° or 41° C. — there is a sudden increase in
the quantity of carbon dioxide given off. Moreover, in an isolated
muscle the total quantity of carbon dioxide obtainable during rigor is
markedly less if the muscle has been previously tetanized. From this
it has been argued that the hypothetical substance (' inogen '), the
decomposition of which yields carbon dioxide in contraction, is also
the substance which decomposes so rapidly in rigor; that a given
amount of it exists in the muscle at the time it is removed from the
influence of the blood; and that this can all ' explode ' either in con-
traction or in rigor, or partly in the one and partly in the other.
However, according to Fletcher, there is no increase in the amount
of carbon dioxide given off during tetanus by an excised frog's
muscle unless the stimulation is so severe and prolonged as to
hasten the onset of rigor. He therefore supposes that in the con-
traction the decomposition does not proceed quite to the formation
of carbon dioxide, which in the intact body is afterwards liberated
from some more complex carbon-containing waste-product. He
considers that the carbon dioxide yielded by excised muscles is
really performed carbon dioxide, already existing in a state of loose
combination, from which it is displaced by the lactic acid formed
after excision. There is no reason to suppose that any independent
new formation of carbon dioxide occurs within the isolated muscle
in the absence of a good supply of oxygen. However this may be,
there is good evidence that oxygen is used up in recovery processes
after the contraction is over, and that these recovery processes are
not completed when oxygen is lacking. Hill's work on the heat
production of muscle (Chapter XIII.) has tended to rehabilitate the
older conceptions, at least to this extent, that his results are in
favour of the view that oxygen is used largely during the recovery
after contraction in reactions ' whereby the molecular machine — like
a steam-engine charging an accumulator — builds up bodies contain
INTERNAL OR TISSUE RESPIRATION *7i
ing considerable amounts of potential energy which (like the accu-
mulator) can be discharged by appropriate stimuli.'
The respiration of muscles in situ can be studied by collecting
samples of the blood coming to and leaving them and analyzing the
gases. The mere difference of colour between the venous and
arterial blood of a muscle, or other active organ, is sufficient to show
that oxygen is taken up and carbon dioxide given out by it to the
blood. This is the case in muscle sat rest, and even in muscles
with artificial circulation after they have become inexcitable. In
active muscles more oxygen is used up and more carbon dioxide
produced than in the resting state. Chauveau and Kaufmann, in
their experiments on the levator labii superioris musck of the horse in
feeding, found that the consumption of oxygen and the production
of carbon dioxide might be many times as great in activity as in rest.
Thus in one experiment the amount of oxygen taken in, expressed
in c.c. per gramme of muscle per minute, was 0-008 during rest, and
0-14 during work; the corresponding quantities for the carbon dioxide
given off were 0-006 and 0-18. The respiratory quotient rose to 1-3 in
two experiments, and even to 1-7 in a third, snowing that the increase
in the production of carbon dioxide was relatively greater than the
increase in the intake of oxygen. These experiments were performed
under conditions so normal that the animal continued to eat its hay
with seeming unconcern throughout the observations, although these
involved the exposure of the main bloodvessels of the muscle, and the
collection of samples of blood from them.
By means of the modern technique permitting the use of small
quantities of blood for the gas analysis, similar experiments have been
performed on a muscle as small as the cat's gastrocnemius. In one
experiment it was found that as a result of stimulation of the sciatic
lasting about 25 seconds the intake of oxygen was increased for at least
220 seconds. In this time the muscle used up 0-75 c.c. of oxygen, as
compared with 0-26 c.c., which it would have consumed had it not been
stimulated (Verzar).
Nature of the Oxidative Process. — When we have recognized the
cells as the seat of oxidation, the question immediately presents
itself, How do they accomplish the feat of burning such masses of
food substances as can only be rapidly oxidized in the laboratory
at the temperature of the body by the most energetic chemical
reagents ? The researches of late years have furnished a key to
the solution of this long-standing puzzle by demonstrating the
existence in the tissues of oxidizing ferments or oxydases. Of these,
one of the most widely distributed is a ferment which splits off
oxygen from hydrogen peroxide. Since any oxidation produced
is only secondary to this decomposition, ferments which decompose
hydrogen peroxide are often spoken of as catalases, to distinguish
them from the oxydases proper. A catalase is found in practically
all the tissues of the body, as well as in vegetable cells, and we have
already mentioned instances of its action in connection with the
oxidation of the guaiaconic acid in tincture of guaiacum in the
272 RESPIRA TION
presence of the peroxide (p. 76). As regards the activity of this
ferment, blood comes first; then follow spleen, liver, pancreas,
thymus, brain, muscle, and ovary. It is present in the blood-free
organs as well as in the blood. Some tissues, both animal and
vegetable, contain a ferment, .an oxydase, which causes the oxida-
tion of guaiaconic acid in the presence of atmospheric oxygen, and
these do not need peroxide of hydrogen in order to render guaiacum
blue. An allied ferment which also induces the blue colour in
tincture of guaiacum is the so-called laccase found in the most active
form in the latex of the tree from which Japanese lacquer is ob-
tained, but also in many other plants. Many fungi contain a fer-
ment, tyrosinase, which oxidizes tyrosin, and in certain animals
tyrosinases have also been demonstrated. Another well-known
oxidizing ferment in fresh animal tissues is characterized by the
property of forming indophenol by oxidation in an alkaline solution
of paraphenylenediamin and a-naphthol, and may therefore be
termed indophenyloxydase. The colourless solution becomes
reddish or violet. This ferment is contained in pancreas, salivary
glands, spleen, thymus, and bone marrow, but has not been de-
tected in muscle, lungs, brain, kidneys, and other organs. It is
to be expected that other oxydases capable of favouring oxida-
tion of specific kinds of food substances or their decomposition
products will be discovered, but it ought to be remarked that
those at present known are only capable of attacking relatively
simple organic substances, and it would be rash to conclude
that this is the only way in which living protoplasm can bring
about the rapid, but at the same time the regulated, oxidation
which is so characteristic a feature of its activity. Yet the capacity
of the cell to regulate the intensity and the extent of the intra
cellular oxidations would seem to find a simple explanation if we
assign an important role to oxidizing ferments formed by the cell
itself in accordance with its needs. In this connection we may
mention a ferment, aldehydase, which was formerly included
among the oxydases, but is now known to be a hydrolytic enzyme.
It splits aldehydes so as to yield the corresponding acid — e.g.,
salicylic aldehyde is split into salicylic acid and saligenin. Evidence
of its presence in most organs has been obtained.
The Passage of Carbon Dioxide from the Tissues into the Blood.
— Since nearly the whole of the carbon dioxide eventually found in
the blood is formed in the tissues, and only a small amount in the
blood itself, it might be supposed that the partial pressure of the
gas in the tissues would necessarily be greater than in the blood.
This would certainly be true if the whole of the carbon dioxide
was transported in the form of dissolved gas. This, however, is
not the case. Much of it is combined, and as the proportion of
free to combined carbon dioxide in the blood is variable, it may be
INTERNAL OR TISSUE RESPIRATION 273
assumed that it is also variable in the tissues. There is no evidence
and little probability that the variations are always parallel. Quan-
titative and even qualitative differences in the substances which can
bind carbon dioxide are known to exist between the blood and the
tissues, and it is uncertain how much interchange of such compounds
carrying with them combined carbon dioxide, which may after-
wards become dissociated, takes place between the blood and the
tissue lymph or the cells. However probable, then, it may be that
the transportation of carbon dioxide from the cells to the lymph,
and from the lymph to the blood is managed in the same way as
that of the carbon dioxide from the blood to the alveolar air, namely,
by diffusion of the gas in solution, it cannot be said that at present
clear proof of this has been obtained. Results are, indeed, on
record, which purport to show that the partial pressure of carbon
dioxide in various tissues or in physiological liquids which have
been in contact with them is higher than that of the arterial or even
than that of the venous blood. But these results are of unequal
and some of them of doubtful value for the solution of the problem
under discussion.
Lymph, bile, urine, and the serous fluids contain, so much carbon
dioxide that the pressure of that gas in all of them is greater than in
arterial blood, while in lymph alone (taken from the large thoracic
duct) has it been found less than that of venous blood. And it is pro-
bable that lymph gathered nearer the primary seats of its production
(the spaces of areolar tissue) would show a higher proportion of carbon
dioxide. Strassburg found that with a pressure of carbon dioxide in
the arterial blood of 21 mm. of mercury, the pressure in bile was 50 mm. ,
in peritoneal fluid 58 mm., in urine 68 mm., in the surface of the empty
intestine 58 mm. Saliva, pancreatic juice, and milk, also contain much
carbon dioxide. From muscle as much as 15 volumes per too of carbon
dioxide can be pumped out, some of which is free — that is, is given
up to the vacuum alone — while some of it is fixed, and only comes off
after the addition of an acid.
Before leaving the subject of the gaseous exchange between
tissues and blood and between blood and air some important con-
sequences of the form of the dissociation curve of oxyhsemoglobin,
and of the modifications produced in it by change of temperature,
by salts and by acids, must be alluded to. They have been developed
in masterly fashion by Barcroft. The flattening of the hyperbolic
dissociation curve of dialyzed oxyhaemoglobin when the tempera-
ture is raised (Fig. 119) makes it obvious that for any percentage
saturation which can exist in blood as it leaves the systemic capil-
laries, the corresponding partial pressure of oxygen must be much
greater at the body temperature (38° C.) than at 16° C. For haemo-
globin which is 50 per cent, saturated it is twenty-five times as
great. This favours the giving up of oxygen to the tissues by blood
in which the percentage saturation is considerably reduced. On
i8
274 RESPIRA TION
the other hand, the absorption of oxygen in the lungs is not seriously
interfered with, because the available alveolar partial pressure of
oxygen is so high (100 mm. or more) that it can be considerably
diminished without causing any appreciable diminution in the
percentage saturation.
There is evidence that in dialyzed haemoglobin solutions the
haemoglobin is all in the form of single molecules. The addition of
salts as they exist in blood produces a certain amount of aggrega-
tion or clumping of the molecules, and as already pointed out, this
alters the shape of the dissociation curve. The S-shape of the
curve of blood indicates that blood will part with its oxygen at
low oxygen pressures, as in passing through the tissues, much more
readily than a corresponding solution of salt -free oxyhaemoglobin ;
and that it will take up oxygen more easily at high pressures, as
in passing through the lungs. As regards the effect of acids, it
was observed by Bohr (p. 255) that an increase in the carbon dioxide
tension of blood diminishes its combining power for oxygen, and
therefore favours the giving up of oxygen to the lymph and tissues.
This may have an important influence on internal respiration. The
effect is much more marked where the oxygen tension is low than
where it is high, so that in the lungs the taking up of oxygen is
scarcely interfered with even by a high carbon dioxide tension.
According to Barcroft, the combined effect of the increased tem-
perature, the salts and the carbon dioxide of blood (at the partial
pressure of 40 mm. of mercury) is to make possible a diffusion of
oxygen into the tissues at 100 times the speed at which it would
diffuse from a salt-free solution of oxyhaemoglobin at a tempera-
ture of 16° C. This astonishing feat is accomplished without
sensibly decreasing the percentage saturation with oxygen of the
blood passing through the lungs.
SECTION VI. — RELATION OF RESPIRATION TO THE NERVOUS
SYSTEM.
The Respiratory Centre and its Connections. — Unlike the beat of
the heart, the respiratory movements are entirely dependent on the
central nervous system. The ' centre ' which presides over them is
situated in the spinal bulb. It is a bilateral centre — that is, it has
two functionally symmetrical halves, one on each side of the middle
line. Each of these halves has to do more particularly with the
respiratory muscles of its own side, for destruction of one-half of
the spinal bulb causes paralysis of respiration only on that side.
Anatomically the respiratory centre has not been sharply localized,
but it lies lower than the vaso-motor centre, not far from the point
of the calamus scriptorius. Stimulation of this region during apncea
(p. 283) is stated to cause co-ordinated inspiratory movements and
RELATION OF RESPIRATION TO THE NERVOUS SYSTEM 275
widening of the opening of the glottis through abduction of the
vocal cords. The centre is brought into relation with the muscles
of respiration by efferent nerves. The phrenic nerves to the dia-
phragm, and the intercostal nerves to the muscles which elevate
the ribs, are the most important of those concerned in ordinary
breathing. The respiratory centre is further related to afferent
nerves, of which the most influential are those which supply the
respiratory tract itself, particularly the pulmonary fibres and superior
laryngeal branch of the vagus. But almost any afferent nerve may
powerfully affect the centre ; and it is also influenced by fibres pass-
ing to it from the higher parts of the central nervous system.
Section of the spinal cord in animals above the origin of the
phrenic nerves causes complete paralysis of respiration, and con-
sequent death. The phrenics arise from the third and fourth
cervical nerves, and are joined by a branch from the fifth; and in
man fracture of any of the four upper cervical vertebrae is as a rule
instantly fatal. But in one case respiration was carried on, and
life maintained for thirty minutes, merely by the contraction of the
muscles of the neck and shoulders in a man entirely paralyzed
below this level (Bell). Section of the cord just below the origin of
the phrenics leaves the diaphragm working, although the other
respiratory muscles are paralyzed. A case has been recorded of a
man in whom, from disease of the spine in the lower cervical region,
all the ribs became completely immovable. He was able to lead
an active life, and to carry on his business, although he breathed
entirely by his diaphragm and abdominal muscles.
Section of one phrenic is followed by paralysis of the correspond-
ing half of the diaphragm, section of both phrenics by complete
paralysis of that muscle, and although respiration still goes on by
means of the muscles which act upon the ribs, it is usuaUy inadequate
to the prolonged maintenance of life. In the horse, however, not only
has survival been seen after this operation, but the animal, after
the first temporary increase in the frequency of the breathing had
disappeared, could be driven in a light vehicle without any marked
dyspnoea. The phrenic nuclei in the two halves of the cord are
connected across the middle line. For when a semisection of the
cord is made between this level and the respiratory centre in the
medulla, respiratory impulses are still able to reach both phrenic
nerves. In some animals both halves of the diaphragm go on con-
tracting. But when, as usually happens, this is not the case, and
the diaphragm on the side of the semisection has ceased to act, it
at once begins to contract again when the opposite phrenic nerve
is cut, and the respiratory impulse, descending from the bulb, is
blocked out from the direct, and forced to follow the crossed path.
It has been shown that the crossing takes place at the level of the
phrenic nuclei, and nowhere else (Porter).
276 RESPIRATION
The Regulation of the Respiration through the Afferent Vagus
Fibres. — When one vagus is divided, there is little or no change in
the respiratory movements. Half an inch of one vagus nerve has
been excised in removing a tumour, and the patient showed no
symptoms whatever. But section of both vagi in such animals as
the dog, cat and rabbit causes respiration to become much deeper
and slower, the one change for a time compensating the other, so
that the total amount of air taken in and given out, the amount of
carbon dioxide eliminated, and the partial pressure of that gas in
the pulmonary alveoli are not greatly altered. The relative dura-
tion of the two respiratory phases is completely changed, inspira-
tion being much more prolonged than expiration. It has been
shown that the effect is really due to the loss of impulses that nor-
mally ascend the vagi, not to any irritation of the cut ends. For a
nerve can be frozen without exciting it ; and when a portion of each
vagus is frozen, the respiration is affected in precisely the same
way as when the nerves are divided.
After section of both vagi certain fibres coming from the brain
above the respiratory centre appear to take a share in the regulation
of the respiratory movements. The bloodvessels supplying these
fibres, or the centres from which they come, can be blocked by
injection of paraffin wax into the common or internal carotid, or
the bulb can be severed with the knife above the level of the re-
spiratory centre, without any effect being produced upon the breath-
ing, except that the rate is as a rule somewhat lessened. But
when both the vagi and these upper paths are cut the character of
the respiration is changed, exceedingly prolonged inspiratory
spasms alternating with long periods of complete relaxation of the
diaphragm till the animal dies.
From these facts it appears that the periodic
of thft respiratory centre are being continually controlled and modi-
fied by impulses passing up the vagus, and that in the absence of
"tnese impulses a certain degree of control is exercised by the higher
paths, which, however, do not appear to be normally in action, at
any rate to the full measure of their capacity. When the vagi are
severed, the control of the higher paths comes into play, and is
sufficient still to keep the breathing regular, although it is slowed.
When the higher paths are cut off, the vagus of itself is able to regu-
late the discharge. But when both are gone, the respiratory centre,
freed from nervous control, passes into a condition of alternate
spasm and exhaustion. Of the central connections of these upper
paths but little is surely known. The corpora quadrigemina, how-
ever, seem to contain centres which can affect _the respiration.
Certain areas on the cerebral cortex have also been described, the
excitation of which modifies the respiratory movements. There is
no question that the cortex is connected, and extensively connected,
RELATION OF RESPIRATION TO THE NERVOUS SYSTEM 277
with the respiratory centre, since the rate and depth of the co-
ordinated respiratory movements, which are universally acknow-
ledged to involve the activity of the centre, can be altered not only
by the will, but by the most varied psychical events.
The rhythmical excitation of the regulating vagus fibres must
be brought about by either mechanical stimulation of the nerve-
endings in the lungs, due to the alternate stretching and shrinking,
or by chemical stimulation of these endings depending on the changes
that occur with each respiration in the content of oxygen and carbon
dioxide in the alveolar air, and therefore in their pressure (p. 260)
in the blood. Both views have found advocates, but whatever
influence the chemical changes in the blood "may exert, there is no
doubt that the mechanical factors are the more important. That
the vagus is really excited is shown by the fact that a negative varia-
tion (p. 824) is set up in the nerve when the lungs are inflated.
An electrical change is also observed when air is sucked out of the
lungs (Alcock and Seemann, Einthoven).
When the normal excitation of the vagus fibres by expansion of
the lungs is exaggerated by closing the trachea at the end of in-
spiration, the diaphragm immediately relaxes, and a long expira-
tory pause ensues, broken at last by a series of inspirations much
deeper and more prolonged than those which were taking place
before occlusion. When the trachea is occluded at the end of
expiration, a series of deep and long-drawn inspirations occurs, the
first of which begins at the moment when the next normal inspira-
tion ought to have taken place had the windpipe been left free.
The most obvious explanation of these results is that the expansion
of the lungs sets up impulses in the vagi which cut short the in-
spiratory activity of the respiratory centre (inspiration-inhibiting
fibres), while in collapse impulses are set up which excite it to re-
newed inspiratory discharge (inspiration-exciting fibres). Since
ordinary expiration is in the main not associated with active muscular
contraction, the inspiration-inhibiting fibres would be at the same
time expiration-exciting. Clearly this would constitute a so-called
' self-steering ' arrangement, each inspiration leading inevitably to
the succeeding expiration, and each expiration providing the neces-
sary stimulus for the succeeding inspiration. On this hypothesis
section of the vagi must necessarily be followed by slowing of the
respiratory movements, and we have seen that this is the case.
A rival hypothesis is that the automatic activity of the respira-
tory centre leads normally to the discharge of motor impulses to
the inspiratory muscles, which are cut short at each expansion of
the lungs by the inhibitory action of the vagus, the nerve not being
excited during pulmonary collapse, and therefore carrying no in-
spiratory impulses to the centre. On this assumption, we may
think of the centre as being ' wound up ' like a clock, the periodic
278 RESPIRATION
arrival of regulating impulses acting like an escapement movement,
and allowing a certain amount of discharge. When the vagi are
cut, the inspirations are greatly prolonged and deepened, because
the check on the discharge of the centre has been removed.
Attempts have been made by experimental stimulation of the
vagus trunk to determine whether, as a matter of fact, it contains
both inspiratory and expiratory fibres. But the results are neither
so clear nor so constant that we can confidently appeal to them in
making a decision, and even some of the investigators who main-
tain the existence of but one anatomical set of fibres believe that
these are affected differently by different kinds of stimulation —
momentary stimuli, for example, setting up in them impulses
which we may call inspiratory, and long-lasting stimuli impulses
which we may call expiratory.
Excitation of the central end of the cut vagus below the origin
of its superior laryngeal branch, with induction shocks of moderate
Fig. 124. — Respiratory Tracings: JJog. A, normal; B, ettect of stimulation of the
central end of vagus; C, effect of section of both vagi. (Tracing taken as in
Fig. 135, p. 301.) Time-tracing, seconds.
strength, certainly causes quickening of respiration. If the excita-
tion be strong, there is arrest in the inspiratory phase. A brief
mechanical stimulus, or a series of such, has a similar effect. But
chemical stimulation (e.g., with a strong solution of potassium
chloride) or long-continued mechanical excitation like that produced
by stretching or compression of the nerve, or certain kinds of elec-
trical stimulation — for instance, the very weakest induction shocks,
or the closure of an ascending voltaic current* — cause slowing of
the respiratory movements or expiratory standstill. This is also
the usual, though not the invariable result of stimulating the
superior laryngeal, even when weak induction shocks are employed.
With stronger stimulation energetic contractions of the expiratory
muscles may occur. These facts undoubtedly suggest the existence
in the vagus of two kinds of afferent nerve-fibres that affect the
* I.e., a current passing towards the head in the nerve.
RELATION OF RESPIRATION TO THE NERVOUS SYSTEM 279
respiratory centre in opposite ways — inspiratory fibres, which
stimulate it to greater activity of discharge, and expiratory fibres,
which inhibit its action. The latter variety we may suppose to be
more numerous in the superior laryngeal, the former in the pul-
monary branches of the vagus. And there is nothing forced in the
hypothesis that certain kinds of stimuli act particularly on the one
set of fibres, and certain kinds on the other, for we have already
seen an instance of this in studying the differences between the vaso-
constrictor and the vaso-dilator nerves (p. 173).
The most probable conclusion, and the one which best reconciles the
conflicting hypotheses, is that two sets of fibres are present : (i) Fibres
which inhibit inspiration (and cause expiration), and are excited in
ordinary inspiration by the expansion of the lungs. (2) Fibres which
Fig. 135. — Effect of Stimulation of Central End of Vagus in a Cat. Upper Traes,
Respiration; Lower Trace, Blood-Pressure. At the top are the time-trace
(seconds), and below it the signal line, the depression in which indicates the
duration of the excitation. Practically no effect was produced on the respira-
tion, but a fall of blood-pressure with slowing of the heart.
cause inspiration (and inhibit expiration), and are excited in strong
expiration, as in dyspnoea, by the collapse of the lungs, but are not
active in ordinary expiration.
However this may be, the facts we have been discussing have an
importance of their own, apart from any hypothetical explanations
of them. Some of them have been more than once unintentionally
illustrated on man. In one case the left vagus trunk was included
in a ligature with the common carotid. The respiratory move-
ments immediately stopped, the pulse was slowed, and death
occurred in thirty minutes (Rouse). The superior laryngeal fibres,
unlike those of the vagus proper, are not constantly in action, as
section of both nerves has no effect on respiration. Any source of
irritation in the larynx may stimulate these fibres and produce a
RESPIRA TION
cough, which may also be caused by irritation of the pulmonary
fibres of the vagus.
Action of Other Afferent Fibres on the Respiration. — The cutaneous
nerves, and especially those of the face (fifth nerve), abdomen and
chest, have a marked influence on respiration. They can be easily
excited in the intact body by thermal and mechanical stimulation.
A cold bath, for instance, usually causes acceleration and deepening
of the respiratory movements ; and the efficacy of mechanical stimu-
lation of sensory nerves in stirring up a sluggish respiratory centre
is well known to midwives, who sometimes slap the buttocks of a new-
Fig. 126. — Effect of Stimulation of Central End of Brachial Nerve on Respiration
(Upper Tracing) and Blood-Pressure (Lower Tracing) in the Cat. At the top of
the figure are the time-trace (seconds) and the signal line, showing beginning and
end of stimulation.
born child to start its breathing. The reflex expiratory standstill
caused in rabbits by inhalation of such sharp-smelling substances as
ammonia, acetic acid, and tobacco-smoke is due to afferent impulses
passing up the trigeminus fibres from the mucous membrane of the
nose, and is still obtained after section of the olfactory nerves.
Another set of afferent nerves which have been supposed by some
to bear an important relation to the respiratory centre are those
which supply the muscles. We have already noticed that the
frequency of respiration is greatly augmented by muscular exercise.
The simplest explanation would seem to be that afferent muscular
nerves are stimulated either by mechanical compression of their
RELATION OF RESPIRATION TO THE NERVOUS SYSTEM 281
terminal 'spindles/ or by the chemical action on them of certain
waste products produced in contraction. It is quite likely that this
is one way in which the adjustment is achieved. But this is not
the only, and perhaps not the most important, way. For an in-
crease in the respiratory movements is caused by tetanizing the
muscles of a limb whose nerves have been completely severed, and
which is indeed connected with the rest of the body by no other
structures than its bloodvessels. This can only be due to two things :
a direct action on the respiratory centre by the blood that has
p"a"ssjed through, and been altered in, the contracting muscles, or an
action exerted by the blood indirectly on the centre through the
excitation of afferent respiratory nerves whose connection with it
is still intact — for example, the other muscular nerves or the pul-
monary branches of the vagus. That the action is direct is shown
by the fact that after section of the vagi, the sympathetic, and the
spinal cord below the origin of the phrenics, an increase in the
respiratory movements is still produced by tetanizing a limb.
The Chemical Regulation of the Respiration. — However im-
portant the regulation of respiration by afferent nervous impulses
may be, the normal discharge of the respiratory centre is intimately
associated with the gases of the blood.
It is generally acknowledged that the centre may be excited both
by blood that is rich in carbon dioxide and by blood that is poor in
oxygen. Stimulation by deficiency of oxygen has to some minds
presented a metaphysical difficulty — namely, that it is not easy to
see how the absence of a thing could cause stimulation. The diffi-
culty does not exist, but none the less there is some evidence that
when oxygen is lacking the respiratory centre can be excited by
substances like lactic acid, which are easily oxidizable and rapidly
disappear from properly oxygenated blood.
Be that as it may, it has been the subject of long-continued dis-
cussion whether excess of carbon dioxide or deficiency of oxygen is
the more potent stimulus for the respiratory centre. The best evi-
dence points to the conclusion that comparatively small alterations
in the amount of carbon dioxide in the inspired air cause a relatively
great increase in the respiration, while in the case of the oxygen the
departure from the normal proportion must be much more decided
to bring about any notable effect. Nor is it at all out of harmony
with this that, when very large quantities of carbon dioxide (30 per
cent, and upwards in rabbits) are inhaled, a condition of narcosis
comes on without any previous respiratory distress. For many
substances act differently in large and in small doses. HaHane has
pointed out how exquisitely sensitive the respiratory centre is to even
small changes in the partial pressure of carbon dioxide in the alveo-
lar air, and therefore in the arterial blood and the centre itself, and
has demonstrated that this is the way in which the amount of the
282 RESPIRATION
pulmonary ventilation (the volume of air breathed per unit of time)
is chiefly regulated in ordinary breathing.
For instance, an increase of as little as 0-2 per cent, of carbon
dioxide in the alveolar air, corresponding to an increase of 1-4 mm.
of mercury in the partial pressure (p. 247) of the gas, caused an
increase in the pulmonary ventilation of 100 per cent. The alveolar
oxygen pressure had to be diminished to 13 per cent, of an atmo-
sphere before any decided increase in the respiration occurred.
During moderate muscular work the percentage of carbon dioxide
in the alveolar air, and therefore in the hlpn^
causing an increase in the ventilation, and this is nnp of +HP
he hvperpncea associated with
about. In_severe work lack of oxygen, with accumulation of lactic
acid and olher metabolic products, which increase the hydrogen-ion
concentration in the blood and thus stimulate the respiratory
centre or render it excitable by smaller pressures of carbon dioxide,
also plays a part. There is some evidence that in the case of
carbon dioxide also the actual excitation of the respiratory centre is
due to the increased hydrogen-ion concentration. Some physiolo-
gists hold the view that the respiratory centre reacts in the same
way to a given, increase in hvdro^en-ion r.nnrentra+im|_pr> matter
what the~acid may be, and that there is nothing specific in the
action of carbon dioxide. If it be assumed that changes in the
hydrogen-ion concentration of the blood are only caused by sub-
stances like carbon dioxide, which are eliminated by the lungs,
or by substances like lactic acid, which are either got rid of by oxi-
dation or are not liberated into the blood in the presence of a good
oxygen supply, no serious theoretical objection can be urged against
this conclusion. For increased activity of the respiratory centre
would favour the elimination of carbon dioxide and absorption of
oxygen, and in both ways would tend to maintain the normal
hydrogen-ion concentration in the blood. If, however, the hydrogen-
ion concentration can be influenced by substances which are not
directly affected by the respiratory process, it would seem unlikely
that the respiratory centre should blindly respond to such changes
just as if they had been produced by substances, the amount of
which it can effectively control.
To sum up, the regulation of normal breathing is twofold — a chemical
regulation (through the carbon dioxide, possibly by changes produced
in the hydrogen-ion concentration in the blood) of the amount of air
moved into and out of the lungs per unit of time ; and a nervous regu-
lation (chiefly through the vagi] of the rate and depth of the movements
necessary to effect the given amount of ventilation.
When the vagi have been divided, an increase in the carbon
dioxide pressure within certain limits is responded to by an increase
in the total ventilation, just as in the normal animal, but the form
of the response is different. Whereas in the normal animal both
RELATION OF RESPIRATION TO THE NERVOUS SYSTEM 283
the rate and the depth of respiration are increased, in the vagoto-
mized animal there is a marked increase in depth, with little or no
increase in rate (Scott).
When the gaseous exchange in the lungs from any cause becomes
insufficient, the respiratory movements are exaggerated, and ulti-
mately every muscle which can directly or indirectly act upon the
chest -wall is called into play in the struggle to pass more air into
and out of the lungs. To a lesser and greater degree of this exag-
geration of breathing the terms Hyperpncea and Dyspnoea have been
respectively applied. If the gaseous interchange remains insuffi-
cient, or is altogether prevented, asphyxia sets in. Sometimes in
man impending asphyxia from loss of function by a part of the lungs
(with crippling of the lesser circulation), as in pneumonia, may be
warded off by inhalations of oxygen. Increase in the temperature
of the blood circulating through the spinal bulb, as when the carotid
arteries of a dog are laid on metal boxes through which hot water
is kept flowing, also causes dyspnoea (heat-dyspncea.) (p. 3°2). But
if the temperature be too high, the respiratory movements may be
slowed, perhaps by a partial paralysis or inhibition of the respiratory
centre. When the blood is cooled the respiration becomes deeper
and slower, but if the temperature is greatly and suddenly lowered,
the centre may be stimulated and the breathing quickened. In
man the increased temperature of the blood in fever is a cause,
though not the only one, of the increase in the rate of respiration.
Apncea. — The physiological opposite of dyspnoea is apncei. This
condition may be produced in an animal by rapid or prolonged
artificial respiration. It is especially easy to obtain in an animal
in which the circulation through the brain and bulb is interrupted
for a time and then restored, while artificial respiration is being kept
up. Spontaneous respiration returns after a longer or shorter
interval, but if the artificial respiration be still maintained, it again
ceases. In a successful experiment the animal remains without
breathing for many seconds after the artificial respiration is stopped.
In apnosa the chest remains at rest in the expiratory phase if the
lungs have been inflated by the artificial respiration and then allowed
to collapse of themselves (expiratory apnoea), but in the inspiratory
phase if they have been emptied by suction and then permitted of
themselves to expand (inspiratory apnosa). The apnoea is not pro-
duced, as some have thought, by the accumulation of an excess of
oxygen in the blood, for rapid and repeated inflation of the lungs
with hydrogen may cause the condition. Indeed, towards the end
of the apnosic period the venous blood may be very distinctly poorer
in oxygen than normal venous blood. Apnoea is easily caused in
man by a period of deep and rapid breathing and in other ways.
The essential thing in this chemical or true apnoea (apncea vera)
is the lowering of the partial pressure of carbon dioxide in the
alveolar air, and therefore in the arterial blood and the respiratory
284 RESPIRATION
centre. The carbon dioxide is washed out of the body, so to say,
by the excessive pulmonary ventilation.
In addition to chemical apnoea, which is obtainable whether the
vagi are intact or not, a so-called mechanical apnoea, or apncez vagi,
exists — -that is to say, a stoppage of the respiration due to an
inhibitory effect produced through the vagi on the respiratory centre
when the vagus endings in the lungs are excited mechanically by
inflation. Some observers state that this vagus apncea does not
outlast the inflation. Others believe that the results of successive
inflations can be ' summated ' in the centre, giving rise to an apnoea
which persists after stoppage of the artificial respiration. That a
' memory ' of a prolonged rhythmical inflation of the lungs can
impress itself in some way on the respiratory centre is shown by
the curious phenomenon that in resuscitation of the bulb after a
period of anaemia the natural respiration, when it returns, may
have for a short time exactly the same rhythm as the artificial
respiration which has just been stopped.
That the blood when the gaseous exchange in the lungs is inter-
ferea with produces dyspnoea by acting on some portion of the brain
may be shown in an interesting manner by establishing wrhat is
called a cross-circulation in two rabbits or dogs. The vertebral
arteries and one carotid are tied in both animals; the remaining
carotids are divided and connected crosswise by glass tubes, or,
what is better, as it avoids the risk of clotting, they are crossed by-
suturing the cut ends, so that the brain of each is supplied by blood
from the other. When the respiration is artificially hindered or
stopped in one of the animals, it shows no dyspnoea; it is in the
other, whose brain is being fed with improperly ventilated blood,
that the respiratory movements become exaggerated. The point
of attack of the ' venous ' blood has been further localized in the
spinal bulb by the observation that when the brain has been cut
away above it, the cord severed below the origin of the phrenics,
and all other nerves connected with the region between the two
planes of section divided, any interference with the gaseous ex-
change in the lungs is at once followed by dyspnoea.*
Automaticity of the Respiratory Centre. — The question has been
raised whether, in the absence of this ' natural ' stimulation by the
blood, and of the impulses that constantly reach the centre along
its afferent nerves, it would continue to discharge itself, or whether
it would sink into inaction. We have already discussed a similar
question in regard to the cardiac and vaso-motor centres, and the
subject must again present itself when we come to examine the
functions of the central nervous system. In the meantime it is only
necessary to say that there is evidence that it is not the mere
* The conclusion is doubtless correct, but this experiment is not decisive.
For the phrenic nerves themselves contain afferent fibres, the stimulation of
•which can influence the respiration after section of the vagi.
RELATION OF RESPIRATION TO THE NERVOUS SYSTEM 285
presence of carbon dioxide (or other substances) in the blood circu-
lating through the respiratory centre which determines the constant
excitation of the centre, but rather the accumulation of carbon
dioxide, or the increase of hydrogen-ion concentration, in the
centre itself when the partial pressure of that gas in the blood
is raised. The idea that the contimous excitation of the centre
is ' autochthonous ' — in other words, that it is due to an internal
stimulating substance or substances manufactured in the centre
itself, as well as carried to it in the blood — renders it easy to under-
stand that the discharge of the respiratory centre, although modified
by the quality of the blood which circulates in it, is not essen-
tially dependent on it. Indeed, in cold-blooded animals whose
blood has been replaced by physiological salt solution, and (in frogs')
even after the circulation has been stopped altogether by excision
of the heart, quiet, regular breathing may be seen for a considerable
time. Of course, blood is essential for the continued nutrition of the
centre and its connections, and it eventually breaks down and ceases
to discharge. The respiratory discharge is still less dependent for its
initiation upon the arrival of afferent impulses. For after section
of the bulb above the centre, of the cord below the origin of the
phrenics, of the vagi and of the posterior roots of all the upper cer-
vical nerves, the spasmodic respiration which we have already
described as occurring when the vagi and the higher paths have been
severed continues without essential modification. It has also been
observed that during resuscitation of the bulb and upper cervical
cord after a period of anaemia, stimulation of afferent nerves, in-
cluding the vagi, is entirely without influence on the respiratory
movements for some time after respiration has returned, presumably
because the synapses (p. 852) on the afferent paths lying within the
previously anaemic area are as yet unable to conduct the nerve
impulses. Nevertheless, the respiratory centre continues steadily
to discharge itself along the efferent paths, whose synapses are
situated beyond the anaemic region. Section of the bulb above
the level of the respiratory centre, and of the cord below the origin
of the phrenic nerves, in addition to the anaemia, makes no essential
difference in the result. The initial rate of discharge of the centre
thus isolated from afferent impulses is approximately constant in
different experiments (about four a minute in cats).
Spinal Respiratory Centres. — Although the chief respiratory centre
lies in the medulla oblongata, under certain conditions impulses to
the respiratory muscles may originate in the spinal cord. Thus, in
young mammals (kittens, puppies), especially when the excitability
of the cord has been increased by strychnine, in birds and in alli-
gators, movements, apparently respiratory, have been seen after
destruction of the brain and spinal bulb. In adult cats, when
the functions of the brain, medulla, and cervical cord have been
abolished by occlusion of their vessels, similar movements of the
286 RESPIRATION
thoracic and abdominal muscles may be seen, but they are not suffi
cient for effective respiration. No proof has ever been given that
in the intact organism the spinal cord below the level of the bulb
takes any other part in respiration than that of a mere conductor of
nerve impulses; and it is not justifiable to assume the existence of
automatic spinal respiratory centres on the strength of such experi-
ments as these.
Death after Double Vagotomy. — Alterations in the rhythm of respira-
tion are not the only effects that follow division of both vagi (or vago-
sympathetics) in the neck. In certain animals, at least, this operation
is incompatible with life. In the rabbit, as a rule, death takes place in
twenty-four hours. A sheep may live three days, and a horse five or
six. Dogs often live a week, occasionally a month or even two, and in
rare instances they survive indefinitely. The most prominent symp-
toms (in the dog), in addition to the marked and permanent slowing
of respiration, quickening of the pulse and contraction of the pupils,
are difficult deglutition, accompanied by frequent vomiting and pro-
gressive emaciation. The appetite is sometimes ravenous, but no
sooner is the food swallowed than it is rejected ; and this is particularly
true of water or liquid food. Sometimes the rejected food is simply
regurgitated after having reached the lower end of the oesophagus,
without entering the stomach. The fatal result is usually caused, or
at least preceded, by changes of a pneumonic nature in the lungs. The
precise significance of the pulmonary lesion is obscure. But it would
seem that paralysis of the laryngeal and cesophageal muscles, with the
consequent entrance of saliva, food, or foreign bodies, carrying bacteria
into the lungs, is responsible to a great extent. And when only a partial
palsy of the glottis is produced, by dividing the right vagus below the
origin of the recurrent laryngeal, and the left as usual in the neck, pneu-
monia either does not occur or is long delayed . It may be that the tissue
of the lungs is rendered particularly susceptible to such insults in conse-
quence of trophic or vascular changes induced by section of the pul-
monary and cardiac fibres in the vagi. It may be quite clearly demon-
strated, however, in animals which live for some weeks, that, not-
withstanding the paralysis of the glottis associated with aphonia, no
pulmonary symptoms may be present till a day or two before death.
The picture presented in these cases is that of an animal suffering,
above all, from alimentary disturbances. The respiration is, to be sure,
very different from the normal in frequency, depth, and type, but there
is nothing to suggest that the lungs are the seat of any pathological
process. Suddenly the picture changes. Pulmonary symptoms ob-
trude themselves. The physical signs of consolidation of the lungs
may be detected, and in a short time the animal is inevitably dead.
Occasionally the determining cause of the pulmonary lesion seems to
be some external circumstance, as a sudden fall of the air temperature.
The idea is exceedingly apt to present itself to the observer that the
pneumonia is an accident, an acute intercurrent affection breaking the
course of a chronic malnutrition, which in any case must have ended
in death. Of course, the vagotomized animal is predisposed to this
accident, but there is no definite time after section of the nerves at
which it must take place. The vomiting is certainly connected with the
paralysis and consequent dilatation of the oesophagus ; and by previously
making an artificial opening into the stomach or by a surgical prophy-
laxis still more heroic, the establishment of a double gastric and
oesophageal fistula (p. 4OT). death may be prevented for many months.
Elimination of all the pulmonary fibres of the vagi, by extirpation of
RELATION OF RESPIRATION TO THE NERVOUS SYSTEM 287
one lung, followed after an interval by section of the opposite vagus
in the neck, is not fatal in rabbits. This is also in favour of the view
that in double vagotomy the stress falls mainly on the digestive system .
Innervation of the Bronchial Muscles. — Both constrictor and
dilator fibres for the bronchi are contained in the vagus. They are
not constantly in action, but can be reflexly excited, most easily
(in the dog and cat) by stimulating the nasal mucous membrane,
and particularly a small area well back upon the nasal septum.
Cauterization of the corresponding area in man is said to give per-
manent relief in certain cases of spasmodic asthma, a condition in
which the recurrent attacks of dyspnoea seem, according to the most
generally accepted view, to be associated with spasm of the bronchial
muscles.
Special Modifications of the Respiratory Movements. — Cheyne-
Stokes Respiration is the name given to a peculiar type of breathing,
marked by pauses of many seconds alternating with groups of
respirations. In each group the movements gradually increase to
a maximum amplitude, and then become gradually shallower again,
till they cease for the next pause. The phenomenon often occurs in
certain diseases of the brain and of the circulation, and pressure on
the spinal bulb may produce it. In cats in which the circulation
in the brain and medulla oblongata has been interrupted for a time
and then restored it is often noticed at a certain stage of resuscita-
tion of the respiratory centre. In frogs, Cheyne-Stokes breathing
has been observed as the result of interference with the circulation
in the spinal bulb, ' drowning,' or ligature of the aorta, and also as
a consequence of removal of the brain, or parts of it (hemispheres
and optic thalami). But it is not peculiar to pathological conditions,
being also seen, more or less perfectly, in normal sleep, especially in
children, in healthy men at high altitudes, in hibernating animals,
and in morphine and chloral poisoning.
Well-marked Cheyne-Stokes breathing can be obtained experi-
mentally in normal persons in a variety of ways. If, for example,
the subject is caused to breathe deeply and frequently for about two
minutes, so as to produce a prolonged apncea, the respiration, when
it is resumed spontaneously, is of the Cheyne-Stokes type (Haldane).
The explanation given by Haldane is that the fall in the partial
pressure of the oxygen in the pulmonary alveoli (p. 283) during the
primary apnoea, with the consequent fall of oxygen pressure in the
arterial blood and the respiratory centre, leads to the production
of lactic acid in the respiratory centre and elsewhere, which stimu-
lates the centre in the same way as carbon dioxide, and thus, permits
it to be excited by a smaller partial pressure of carbon dioxide than
that normally necessary. As soon as the pressure of carbon dioxide,
which is increasing during the period of apnoea, has reached the
exciting value breathing is resumed. The respirations, beginning
as very feeble movements, rapidly increase in strength till the
288 RESPIRA TION
breathing becomes quite deep or actually dyspnoeic. The store of
oxygen is replenished by this thorough ventilation of the lungs, the
changes in the excitability of the respiratory centre due to lack of
oxygen disappear (perhaps by oxidation of the lactic acid), and the
centre relapses into a period of repose. During this period of apnoea
the oxygen pressure sinks once more to the point at which the change
in the excitability of the respiratory centre by carbon dioxide occurs,
and the breathing again starts. In pathological cases the want of
oxygen may be associated either with deficient circulation through
the bulb-centre or with deficient intake by the lungs. The adminis-
tration of oxygen through a mask has been shown in such cases to
abolish the periodicity in the respiration, and to render it more
normal.
Peculiarly modified, but more or less normal, respiratory acts are
coughing, sneezing, yawning, sighing, and hiccup.
A cough is an abrupt expiration with open mouth, which forces
open the previously closed glottis. It may be excited reflexly from
the mucous membrane of the respiratory tract or stomach through
the afferent fibres of the vagus, from the back of the tongue or
mouth, and (by cold) from the skin.
Sneezing is a violent expiration in which the air is chiefly expelled
through the nose. It is usually excited reflexly from the nasal
mucous membrane through the branch of the fifth nerve which
supplies it. Pressure on the course of the nasal nerve will often
stop a sneeze. A bright light sometimes causes a sneeze, and so in
some individuals does pressure on the supra-orbital nerve, when the
skin over it is slightly inflamed.
Yawning is a prolonged and very deep inspiration, sometimes
accompanied with stretching of the arms and the whole body. It
is a sign of mental or physical weariness.
A sigh is a long-drawn inspiration, followed by a deep expiration.
Hiccup, or hiccough, is due to a spasmodic contraction of the dia-
phragm, which causes a sudden inspiration. The abrupt closure of
"the glottis cuts this short and gives rise to the characteristic sound.
The following readings of the intervals between successive spasms
were obtained in one attack: 13 sees., 12 sees., 15 sees., 9 sees.,
14 sees., etc. — i.e., one-fourth or one-fifth of the frequency of the
ordinary respiratory movements. The mere fixing of the attention
on the observations soon stopped the hiccup.
Hiccup is generally considered to be a reflex movement, brought
about through the respiratory centre by afferent impulses originating
in the stomach. The irritation may be merely due to some slight
digestive disturbance set up by overfilling of the stomach, perhaps.
This is exceedingly common in infants. But persistent hiccup may
also be a distressing symptom of very formidable diseases — for
example, carcinoma of the pylorus. Experimentally, reflex con-
tractions of the diaphragm can sometimes be elicited by stimulation
INFLUENCE OF RESPIRATION ON THE, BLOOD-PRESSURE 289
of the central end of the vagus at a time when no ' spontaneous
respiratory movements are going on. This has been observed, for
instance, in cats during resuscitation of the brain after a period of
anaemia. In man also, in a case of Cheyne- Stokes respiration accom-
panied by hiccup, it was seen that the hiccup persisted during the
periods of apncea. If the respiratory centre is the centre 'for the
hiccup reflex, it can therefore be excited by afferent nervous im-
pulses at a time when it is not excited by the normal chemical
stimulus (MacKenzie and Cushny).
SECTION VII. — THE INFLUENCE OF RESPIRATION ON THE BLOOD-
PRESSURE.
We have already stated, in treating of arterial blood-pressure
(p. in), that a normal tracing shows a series of waves corresponding
with the respiratory movements.
The relationship between the respiratory phases and the rise and
fall of the blood- pressure is not by any means a simple and invariable
one. It depends upon a number of factors, which need not be
equally influential under different conditions or in different animals
(Lewis). Something depends upon the rate, something upon the
relative preponderance of costal and abdominal respiration, and
something probably upon the size of the animal. For instance, an
inspiratory rise of blood-pressure occurs in man with pure dia-
Insp. —
Inso -
(\ ' A A A
Fig. 127. — Respiratory Waves in the Blood-Pressure: Simultaneous Tracings of
Movements of Respiration and of Radial Pulse in Human Subject (Lewis). In
A the respiration was diaphragmatic; in B, costal. In A the respiratory tracing
was taken from the abdominal wall; in B, from the chest.
phragmatic, and a fall with pure thoracic, breathing (Fig. 127). In
cats with fairly fast and not very deep respiration the blood-pressure
rises in expiration and sinks in inspiration. With deep and slow
respiration the opposite effect may, upon the whole, be seen. In
dogs, according to Einbrodt, although the mean blood-pressure is
falling for a short time at the beginning of inspiration, it soon reaches
its minimum, then begins to rise, and continues rising during the
19
RESPIRA TION
rest of this period. At the commencement of expiration it is still
mounting, but soon reaches its maximum, begins to fall, and con-
tinues falling through the remainder of the expiratory phase.
A partial explanation is afforded by a consideration of the mechan-
ical changes produced in the thorax by the respiratory movements.
Of these, the influence of variations in the intrathoracic pressure
on the filling of the heart is of special importance. With deep
abdominal breathing the changes of intra-abdominal pressure also
affect the filling of the heart, an increase of pressure (in inspiration)
tending to cause more blood to be squeezed from the abdominal
veins towards the chest. The changes of vascular resistance in the
lungs, due to the alteration in the calibre of the pulmonary vessels,
may also contribute, but, for such variations of intrathoracic
pressure as normally occur, only in a minor degree. The changes
in the vascular capacity of the lungs — that is, in the amount of
blood contained in the pulmonary vessels — are of importance espe-
cially in delaying or accelerating the alterations of blood- pressure in
the systemic arteries due to the other factors.
The intrathoracic pressure, which, as we have seen, is always less
than that of the atmosphere, unless during a forced expiration when
the free escape of air from the lungs is obstructed, diminishes in
inspiration and increases in expiration. The great veins outside the
chest, the jugular veins in the neck, for example, are under the
atmospheric pressure, which is readily transmitted through their
thin walls, while the heart and
thoracic veins are under a
smaller pressure. The venous
blood both in inspiration and ex-
piration will, accordingly, tend
to be drawn into the right
auricle. In inspiration the ven-
ous flow will be increased, since
the pressure in the thorax, and
therefore in the pericardial
cavity, is diminished; and upon
the whole more venous blood
will pass into the right heart
during inspiration than during expiration. Now, the right ventricle is
not in general working as hard as it can work. Hence, the excess of
blood which reaches it during an inspiration is at once sent into the
lungs, although not even the first of it can have passed through to
the left side of the heart at the end of the inspiration, since the
pulmonary circulation-time (four to five seconds in a small dog,
two to three seconds in a rabbit) is longer than the time of a com-
plete inspiration at any ordinary rate. The increase in the quantity
of blood pumped into the pulmonary artery will, if not counteracted
by other circumstances, tend to raise the blood-pressure in the
Fig. 128. — The upper tracing shows the
respiratory movements in a rabbit with
rather deep and slow diaphragmatic
breathing; the lower tracing is the
blood-pressure curve; /, inspiration;
E, expiration, including the pause.
INFLUENCE OF RESPIRATION ON THE BLOOD-PRESSURE 291
artery and its branches, and therefore at once to accelerate the out-
flow through the pulmonary veins. This will be aided if at the
same time the vascular resistance in the lungs is reduced, as is
generally stated to be the case. The left ventricle, like the right,
is capable of discharging more blood than it ordinarily receives. The
excess of blood coming to it is easily and promptly ejected. The
systemic arteries are better filled and the arterial pressure rises.
In expiration the contrary will happen. The return of blood to
the thorax will be checked. This is well shown by the swelling of
the veins at the root of the neck in expiration, their shrinking in
inspiration, the so-called respiratory venous pulse. Less blood
being drawn into the right heart, less will be pumped into the pul-
monary artery, in which the pressure will, of course, fall. The out-
flow into the left auricle will thus be diminished — all the more if in
the expiratory phase the vascular resistance in the lungs is increased
— and the systemic arterial pressure will be lowered. In both cases,
however, the change seen in the blood-pressure curve will be belated,
and will not coincide exactly with the commencement of the inspira-
tion or the expiration. If it is delayed for a period about equal to
the length of an inspiration or an expiration, the blood-pressure
will be seen to sink in inspiration and to rise in expiration. If
the period of delay is less than this, the pressure will be mounting
during a part of each respiratory phase and falling during the
rest. As to the explanation of the delay, several factors may be
concerned.
The negative pressure of the thorax acts on the aorta, as well as
on the thoracic veins, although, on account of the greater thickness
of its walls, to a smaller extent than on the veins. The diminution
of pressure in inspiration tends to expand the thoracic aorta, and to
draw blood back out of the systemic arteries, while expiration has
the opposite effect. And although the hindrance caused in this way
to the flow of blood into the arteries during inspiration, and the
acceleration of the flow during expiration may not be great, they
will, of course, be better marked in small animals with compara-
tively yielding arteries than in large animals. Yet, whether great
or small, the tendency will be to diminish the pressure in the one
phase and increase it in the other. As soon as the changes of pres-
sure produced by alterations in the flow of venous blood into the
chest and through the lungs are thoroughly established, the arterial
effect will be overborne; but before this happens — that is, at the
beginning of inspiration and expiration — it will be in evidence, and
will help to delay the main change.
Another factor in this delay is found in the changes of vascular
capacity which take place in the lungs when they pass from the
expanded to the collapsed condition. The expansion of the lungs
in natural respiration causes a widening of the pulmonary capillaries,
with a consequent increase of their capacity and diminution of their
2Q2
RESPIRA TION
resistance. When the vessels at the base of the heart are ligatured
either at the height of inspiration or the end of expiration, so as
to obtain the whole of the blood in the lungs, it is found that they
invariably contain more blood in inspiration than in expiration.
During inspiration, as we have seen, the right ventricle is sending
an increased supply of blood into the pulmonary artery; but before
any increase in the outflow through the pulmonary veins can take
place, the vessels of the lung must be filled to their new capacity.
The first effect, then, of the lessened vascular resistance of the lungs
in inspiration is a temporary falling off in the outflow through the
aorta, and therefore a fall of arterial pressure. As soon as a more
copious stream begins to flow through the lungs, this is succeeded
by a rise. In like manner the first effect of expiration, which in-
creases the resistance and diminishes the capacity of the pulmonary
vessels, is to force out of the lungs into the left auricle the blood
for which there is no room. This causes a rise of arterial blood-
pressure, succeeded by a fall as soon as the lessened blood- flow
through the lungs is established.
The changes in the diastolic capacity of the chambers of the heart
itself, with the changes of pericardial pressure, must also act in the
Fig. 129. — Effect on Blood-Pressure of Inflation of the Lungs: Rabbit. Artificial
respiration stopped in inflation at i. Interval between 2 and 3 (not reproduced)
51 seconds, during which the curve was almost a straight line. Time tracing
shows seconds.
same direction. It is obvious, then, how greatly the rate and depth
of respiration in relation to the size of the animal and the other cir-
cumstances already mentioned may influence the time relations of
the respiratory oscillations in the arterial pressure curve, so that we
ought not to expect them to be absolutely constant.
In artificial respiration oscillations of blood-pressure, synchronous
with the movements of the lungs, are also seen. During inflation
(inspiration) the arterial pressure rises; during deflation (expiration) it
falls. When artificial respiration is stopped at the height of inflation
and the lungs kept inflated (Fig. 129), the arterial blood-pressure falls
rapidly, and continues low until the rise of asphyxia begins. In the
INFLUENCE OF RESPIRATION ON THE BLOOD-PRESSURE 293
fall of pressure the increased intrathoracic pressure due to the inflation
is an important factor. When the respiration is stopped in collapse,
instead of a fall a steady rise of pressure occurs (as in Fig. 84, p. 188).
This ultimately merges in the elevation due to asphyxia, which shows
itself sooner than in inflation. When the tracheal cannula is closed in
natural respiration, no initial fall of pressure takes place (Fig. 130).
Besides the mechanical effects of the respiratory movements on
the circulation, it may be influenced by changes in the cardio-
inhibitory and vaso-motor centres synchronous with the rhythm of
the respiratory centre. In many animals (the dog, for instance)
and in man, it can be very easily made out that the rate of the heart
is greater during inspiration, especially towards its end, than in
expiration. The phenomenon is especially distinct in deep and
slow respiration. It is caused by a rhythmical rise and fall in the
activity of the cardio-inhibitory centre, synchronous with the
respiratory movements, for the difference disappears after division
of both vagi. The normal respiratory oscillations of blood-pressure
are not due in any great degree to such changes in the rate of the
heart, for they persist after section of the vagi, and they are seen in
animals like the rabbit, in which in ordinary breathing little or no
variation in the rate of the heart is connected with the phases of
respiration. The most probable explanation of the respiratory
Fig. 130.— Blood-Pressure Tracing: Rabbit, under Chloral. Natural respiration
stopped at I in inspiration, at E in expiration. The mean blood-pressure is
scarcely altered; but the respiratory waves become much larger owing to the
abortive efforts at breathing. Time tracing shows seconds.
variations in the pulse-rate is that the respiratory centre, when it is
discharging itself in inspiration, sends out impulses as a sort of over-
flow along fibres connecting it with the cardio-inhibitory centre.
These increase the tone of that centre, but, owing to the long latent
period of the cardio-inhibitory apparatus, the inhibition does not
reveal itself till the succeeding expiration. It may be, however, that
the impulses discharged from the respiratory centre in inspiration
diminish the tone of the cardio-inhibitory centre, and thus lead to
acceleration of the heart towards the end of the inspiratory phase.
In certain pathological conditions the influence of the respiration on
the pulse-rate is exaggerated (so-called ' respiratory arhythmia ').
Traube-Hering Curves. — Rhythmical changes in the activity of
the vaso-motor centre, also associated with periodic discharges from
294 RESPIRATION
the vaso-motor centre, also associated with periodic discharges from
the respiratory centre, may be observed under certain conditions —
e.g., when in an animal paralyzed by curara, and therefore unable to
breathe spontaneously, the artificial respiration is stopped for a time.
If such a dose of curara be given as will still permit slight spontaneous
respiration to go on, and both vagi be cut, it can be seen on stopping
the artificial respiration that the waves on the blood-pressure curve
are exactly synchronous with the slow respiratory movements. The
Traube-Hering waves sink in inspiration and rise in expiration.
The fact that they have invariably a longer period than the
natural respiratory movements indicates that they are not concerned
in the production of the normal respiratory oscillations of arterial
pressure. Probably the reason why the Traube waves appear after
section of the vagi is the increased vigour of the slow respiratory
discharges, coupled with a hyperexcitability of the vaso-motor
centre, due to the long pauses in the aeration of the blood. In the
asphyxial rise of pressure in a curarized dog they are constantly
seen, and are often observed when the circulation in the medulla
Fig. 131. — Traube-Hering Waves as the Blood-Pressure is falling during Occlusion
of the Cerebral Arteries in a Cat.
oblongata is in any way interfered with (Fig. 131). In addition to
the true Traube-Hering waves, other and much longer periodic
variations in the blood-pressure are sometimes noticed. If spon-
taneous respiration is going on, their long sweeping curves then show
the ordinary respiratory waves superposed on them.
The normal respiratory oscillations in the veins, as might be
expected, run precisely in the opposite direction to those in the
arteries, and so do the Traube-Hering curves. The increased flow
from the veins to the thorax during inspiration lowers the pressure
in the jugular vein, while it increases the pressure in the carotid.
The constriction of the small bloodvessels to which the Traube-
Hering curves are due increases the blood-pressure in the arteries,
because it increases the peripheral resistance to the blood- flow; in
EFFECTS OF BREATHING CONDENSED AND RAREFIED AIR 295
the veins it lowers the pressure, because less blood gets through to
them. Accordingly, when the Traube-Hering curve is ascending in
the carotid, it is descending in the jugular.
The respiratory variations in the volume of the brain, which are
so striking a phenomenon when a trephine hole is made in the
skull, but which can also take place, thanks to the displacement of
cerebro-spinal fluid (p. 174), when the cranium is intact, have by
some been attributed to interference with the venous outflow from
the cranial cavity during expiration, and by others to those changes
in the arterial pressure whose causes we have just been discussing.
The truth is that neither factor is exclusively concerned. The ques-
tion turns largely upon the time-relations of the movements. The
swelling of the brain is sometimes synchronous with expiration, and
the shrinking with inspiration. Here the damming back of the
blood in the sinuses when the outflow is checked by the expiratory
rise of pressure in the thoracic veins either conspires with an expira-
tory rise of arterial pressure or is more than enough to counter-
balance an expiratory fall of pressure in the cerebral arteries if the
respiratory conditions are such as to lead to an expiratory fall. But
sometimes the dura mater bulges into the trephine hole in inspira-
tion and sinks down in expiration. Here the increase in the volume
of the brain produced by the increased pressure in the arteries and
capillaries in inspiration is more than sufficient to counterbalance
the quickened escape of blood from the cerebral veins.
SECTION VIII. — THE EFFECTS OF BREATHING CONDENSED AND
RAREFIED AIR.
These are— (i) mechanical, shown chiefly by changes in the cir-
culation, in the blood-pressure, for instance ; (2) chemical.
The mechanical effects differ according to whether the whole body,
or only the respiratory tract, is exposed to the altered pressure.
When the trachea of an animal is connected with a chamber in
which the pressure can be raised or lowered, it is found that at first
the arterial blood-pressure rises as the pressure of the air of respira-
tion is increased above that of the atmosphere. But a maximum
is soon reached; and when respiration begins to be impeded, the
pressure falls in the arteries and increases in the veins. When the
pressure of the air in the chamber is diminished a little below that
of the atmosphere, there is a slight sinking of the arterial blood-
pressure, which rises if the air-pressure is further diminished.
It is clear that any change of the air-pressure which tends to diminish
the intrathoracic pressure will favour the venous return to the heart,,
and therefore, if the exit of blood from the thorax is not proportionally
impeded, the filling of the arteries. An increase in the mtra-alveolar
pressure must tend on the whole to increase, and a diminution in it to
lessen, the pressure inside the thorax, which always remains equal to
the intra-alveolar pressure, minus the elastic tension of the lungs.
296 REBP1RA TlOtf
Breathing compressed air should, therefore, under the conditions
described, be upon the whole unfavourable to the venous return to the
heart and to the filling of the arteries, and the arterial pressure should
fall ; while breathing rarefied air should have the opposite effect. But
a very great diminution of the intrathoracic pressure is not necessarily
favourable to the circulation, since the auricles are then unable to con-
tract perfectly.
Certain chest diseases have been treated by the use of apparatus by
which the patient is made to breathe either compressed or rarefied air ;
or to inspire air at one pressure and to expire into air at another pressure.
And it has, upon the whole, been found, in agreement with theory,
that condensed air cannot help the circulation however it is applied, but
always hinders it; while rarefied air aids the circulation both in inspira-
tion and in expiration. But
the increased work of the in-
spiratory muscles may coun-
terbalance the advantage.
Valsalva's experiment,
which is performed by closing
the mouth and nostrils after
a previous inspiration, and
Fig. 132. — Pulse Tracing in Valsalva's Experi- then forcibly trying to expire ,
ment (Rollett). is an imitation of breathing
into compressed air. The
intrathoracic pressure is raised, it may be, to considerably more than
that of the atmosphere; the venous return to the heart is impeded,
and may be stopped ; and the pulse curve is altered in such a way as
to indicate first an increase and then a decrease of the arterial blood-
pressure succeeded by a second rise (Fig. 132).
Muller's experiment, which should be bracketed with Valsalva's,
consists in making, after a previous expiration, a strong inspiratory
effort with mouth and nostrils closed. Here the intrathoracic pressure
is greatly diminished, more blood is drawn into the chest, and upon the
whole effects opposite to those of Valsalva's experiment are produced
(Fig. 133). Neither experiment is
quite free from danger. In both
the dicrotism of the pulse becomes
more marked.
When the whole body is sub-
jected to the changed pressure,
J . , ,, Fig. 133.— Pulse Tracing in Muller s
as in a balloon or on a mountain, Experiment (Rollett).
in a diving-bell or a caisson used
in building the piers of a bridge, the conditions are very different.
For the blood-pressure, the intrathoracic pressure, and the intra-
alveolar pressure, all fall together when the pressure of the atmo-
sphere is diminished, and all rise together when it is increased. It
is possible not only to live, but to do hard manual labour, at very
different atmospheric pressures.
As regards the chemical effects of condensed and rarefied air,
Loewy found that the quantity of oxygen absorbed by a man breath-
ing air in the pneumatic cabinet remained constant at all pressures
between about two atmospheres and half an atmosphere. At 440 mm.
of mercury dyspnoea became evident ; but if the person was now made
to work, the dyspnoea passed away, and did not again manifest itself
EFFECTS OF BREATHING CONDENSED AND RAREFIED AIR 297
till the pressure was reduced to 410 mm. There are towns on the
high tablelands of the Andes, and in the Himalayas, where the
barometric pressure is not more than 16 to 20 inches, yet the in-
habitants feel no ill effects. And in the caissons of the Forth Bridge
the workmen were engaged in severe toil under a maximum pressure
of over three atmospheres, while in the caissons of the St. Louis
Bridge in America a maximum pressure of over four atmospheres
(i.e., more than three atmospheres in addition to the ordinary air-
pressure) was reached.
Inside the caissons the men sometimes suffer from pain and noise in
the ears, due to excessive pressure on the external surface of the tym-
panic membrane. If the pressure in the tympanum is raised by a
swallowing movement, which opens the Eustachian tube and permits
air to enter it, the symptoms generally disappear. The suddenness of
the change of pressure has much to do with its effects, and it is found
that the men are most liable to dangerous symptoms while passing
through the air-lock from the caissons to the external air. It may be
concluded, from experiments on animals, that some of the most serious
of these — the localized paralysis usually affecting the legs (paraplegia)
and the circulatory disturbances — are due to the formation of gaseous
emboli, by the liberation of nitrogen in the blood and other body-
fluids when the pressure is abruptly reduced. And, indeed, it is found
that the symptoms can often be caused to disappear, both in animals
and men, by promptly subjecting them again to compressed air. To
avoid gas embolism on decompression, the shift should be so short that
the body-fluids do not become fully saturated with nitrogen, and the
decompression should be slow. Even with a rate of decompression of
twenty minutes for each atmosphere of excess pressure, the equilibrium
between the dissolved and the atmospheric nitrogen is not entirely
established fifteen minutes after decompression.
But that the action of air under a high pressure is not merely mechan-
ical follows from the singular fact that in pure oxygen at a pressure
of 4 to 5 atmospheres, which corresponds to air at 20 to 25 atmospheres,
convulsions are often produced in vertebrate animals, while exposure
to 6 to 25 atmospheres of oxygen causes dyspnoea and coma, usually
without convulsions. All animals, so far as investigated, are instantly
convulsed and killed under a pressure of 50 atmospheres of oxygen
(Hill and Macleod). Even seeds and vegetable organisms in general
are killed in a short time in oxygen at 3 to 5 atmospheres; and an
atmosphere of pure oxygen, equal to 5 atmospheres of air, hinders
the development of eggs. Lorrain Smith has shown that in small birds
and mice exposure for many hours to a pressure of between I and 2
atmospheres of pure oxygen causes pneumonia. He confirms Bert's
observations on the acute toxic effects produced by higher pressures,
and supposes that in the production of caisson disease the special action
of the oxygen at high pressure may play a part as well as the rapid
decompression. Even atmospheres containing 80 to 96 per cent, of
oxygen under normal barometric pressure produce in rabbits, in 24 to
48 hours, congestion and oedema of the lungs, and finally a fibrinous
broncho-pneumonia. Still smaller oxygen pressures may cause similar
effects in a longer time (Karsner).
When the air-pressure is diminished below a certain limit, death
takes place from asphyxia, more or less gradual according to the
rate at which the pressure is reduced. The haemoglobin cannot get
298 RESPIRA TION
or retain enough oxygen to enable it to perform its respiratory func-
tion; its dissociation tension is no longer balanced by an equal or
greater partial pressure of oxygen in the air. The tension of carbon
dioxide in the blood is also lessened, owing to the dyspnoea and
the consequent increase of pulmonary ventilation.
To such changes, as well as to the cold, some of the deaths in high
balloon ascents must be attributed. Messrs. Glaisher and Coxwell
supposed that they reached the height of 37,000 feet; the former became
unconscious at 29,000 feet (8,800 metres), at which height the amount
of oxygen in the arterial blood would probably not exceed 10 volumes
per cent., but recovered during the descent. The symptoms of the
1 mountain sickness ' so familiar to Alpine climbers (nausea, headache,
and marked depression), the undue hyperpncea produced by muscular
exertion, and the sleep disturbed by irregular breathing, are also mainly
due to deficiency of oxygen in the blood. The most rational prophy-
laxis is to leave the high peaks severely alone. But for the enthusiasts
who cannot do this a portable apparatus for generating oxygen has been
devised. Experiments in the pneumatic cabinet indicate that the
hyperpncea is due to the indirect action of want of oxygen already
referred to in discussing the normal regulation of respiration (p. 281)
— that is, to the formation, in consequence of the insufficient oxygen
supply, of lactic acid or other substances which have the same influence
as carbon dioxide on the respiratory centre — so that less carbon dioxide
is required to excite the centre. Although the hyperpncea leads to a
diminution in the partial pressure of carbon dioxide in the pulmonary
alveoli, there is no evidence that lack of carbon dioxide (' acapnia ') is
the primary cause of mountain sickness (Haldane). It must be remem-
bered, however, that here the influence of the low barometric pressure
is complicated by other conditions. For example, while in the pneu-
matic cabinet, as already stated, diminution of the pressure does not
affect the oxygen consumption, it is relatively much greater on the
high mountain levels both during rest and during work than on the
plains. This is not the case in balloon ascents. And evidence has been
brought forward that changes in the mechanics as well as in the chem-
istry of respiration are concerned (the breathing, for instance, taking
on a periodic character, with some approach to the Cheyne-Stokes type
— p. 287), and that there is something not connected with the want of
oxygen which diminishes the capacity for muscular work. This ' some-
thing ' is perhaps a peculiar excitation of the nervous system in the
fierce light of those high levels, which acts not only on the retina, but
on the skin, and may even affect the distribution of the blood. It is
said that a so-called light bath, as used in the treatment of certain
diseases, may increase the quantity of blood in rabbits by 25 per cent,
in four hours. The shorter wave-lengths which are relatively more
intense in the mountain light are most effective. Recent investigations
of the effects of high mountain climates have been conducted by
Haldane, Henderson, and others, on Pike's Peak, and by Barcroft and
his associates on the Peak of Teneriffe and in the Alps. As already
mentioned, Haldane concluded that there was evidence of oxygen
secretion by the lungs which became more marked with the duration
of residence on the mountain (14,000 feet above sea-level). The total
oxygen capacity, and therefore the total amount of haemoglobin,
gradually increased. The total volume of the blood was but slightly
augmented, and the percentage of haemoglobin rose decidedly. The
changes in the circulation have been especially studied by Schneider,
CUTANEOUS RESPIRATION 299
who found a marked increase in the rate of blood-flow through the
hands, associated with an acceleration of the heart beat, dilatation of
the arterioles and a fall in the venous pressure. In ' aviator's sick-
ness ' the essential factor is also oxygen deficiency.
SECTION IX. — CUTANEOUS RESPIRATION.
It has already been remarked that a frog survives the loss of its lungs
for some time, respiration going on through the skin. Indeed, it has
been calculated that in the intact frog, under ordinary conditions, as
much as three-quarters of the total gaseous exchange may be cutaneous.
Two frogs were seen to live thirty- three days, and one even forty days,
after excision of the lungs. The effect of exclusion of the pulmonary
respiration on the gaseous exchange depends on the previous intensity
of the metabolism. If this is high the gaseous exchange sinks markedly ;
if it is low there is scarcely any alteration. At their maximum efficient y,
the frog's lungs are capable of sustaining a much greater exchange
than the skin. Besides this quantitative, there is a qualitative differ-
ence, the carbon dioxide passing more easily through the skin than the
oxygen, so that the respiratory quotient is increased by elimination of
the lungs. In mammals the structure of the skin is different, and
respiration can only go on through it to a very slight extent. The
amount of carbon dioxide excreted in man, although only about 4 grm.
or 2 litres in twenty-four hours, is much greater than corresponds to
the quantity of oxygen absorbed through the skin. It has been as-
serted, and no doubt with justice, that some at least of the carbon
dioxide given off is due to putrefactive processes taking place on the
surface of the body. Such processes, as has already been pointed out,
seem also responsible in part for the heavy odour of a ' close ' room.
For no harmful products appear to be exhaled from the skin when it is
properly cleansed. In spite of the romantic statements to the con-
trary in ancient and modern books (for instance, the story of the child
that was gilded to play the part of an angel at the coronation of a
medieval pope, but died before the ceremony began), the whole of the
human skin may be coated with an impermeable varnish without any
ill effects. The entire surface of the body of a patient with cutaneous
disease was covered with tar, and kept covered for ten days. There was
not the least disturbance of any normal function. The serious effects
of varnishing the skin in animals are due, not to retention of poisonous
substances, but to increased heat loss. Varnishing is not so rapidly
harmful in large animals like dogs as in rabbits, which have a relatively
great surface and a delicate skin. The danger of widespread superficial
burns is well known. But it is not due to diminished excretion by the
skin, for death occurs when large cutaneous areas remain uninjured.
The patient nearly always dies when a quarter of the whole skin is
burnt; yet the remaining tl.ree-quarters may surely be considered
capable, from all analogy, of making up the loss by increased activity.
One kidney is enough to eliminate the products of the nitrogenous
metabolism of the whole body. It is difficult to see why the excretion
of the trifling amount of solid matter in the perspiration should be
interfered with by the loss of 25 per cent, of the sweat-glands. The real
explanation of the serious effects of extensive superficial burns is
perhaps the excessive irritation of the sensory nerves, which may lead
to changes in the nervous centres, or reflexly in other organs, or the
chemical changes in the damaged tissue, for example, in the blood-
corpuscles, or the transudation of lymph at the injured part, and con-
sequent increase in the concentration of the blood.
300
RESPIRATION
PRACTICAL EXERCISES ON CHAPTER IV.
i. Tracing of the Respiratory Movements in Man. — Pass a tape
through the rings B of the stethograph shown in Fig. 134, and then
around the neck or over
the shoulders, so as to sup-
port the instrument on
the chest at a convenient
height. Fasten tapes to
the hooks and tie
them by a slip-knot
'round the chest. The
tube E is connected
to a recording tambour,
writing on a drum. Or use
the belt stethograph or
spirograph of Fitz (p. 233),
fastening the elastic tube
round the chest with the
chain, and connecting it
with a tambour or the
bellows recorder shown in
Fig. 134. — Stethograph.
Fig. 137. Compare the ex-
tent of the excursion when
the tube is adjusted at different levels over the thorax and abdomen.
2.* Production of Apnoea and Periodic Breathing in Man. — Arrange
for taking tracings of the respiratory movements from a fellow-student
as in i . Let the subj ect of the experiment recline in a perfectly easy
position in an armchair. Let him then breathe deeply and frequently
for about two minutes, so as to produce a prolonged apnoea of about
two minutes' duration. Whenever any desire to breathe returns, the
breathing is to be allowed to take its own course. It may be expected
at first to be of the periodic (Cheyne-Stokes) type.
3. Tracing of the Respiratory Movements in Animals. — (a) Set up
the arrangement shown in Fig. 135, and test whether it is air-tight.
Have also in readiness an induction machine and electrodes arranged
for an interrupted current. Anaesthetize a rabbit with chloral or
ether (p. 217), or a small dogf with morphine and ether, or A.C.E.
mixture. Insert a cannula into the trachea (p. 201), and connect it
with the large bottle by a tube. Connect the bottle with a recording
tambour adjusted to write on a drum, and regulate the amount of the
excursion of the lever by slackening or tightening the screw-clamp.
Set the drum off at slow speed, and take a tracing.
(6) Then disconnect the cannula from its tube. Dissect out the vagus
in the lower part of the neck, pass a ligature under it, but dp not tie it.
Connect the cannula again with the bottle, and while a tracing is being
taken ligature the vagus. Cut below the ligature and stimulate its central
end with weak shocks, marking the time of stimulation on the drum.
Repeat the stimulation with strong shocks, and observe the results.
* This experiment is only to be attempted under the direct supervision of
the demonstrator.
f If a large dog is used the bottle should be omitted, the tracheal cannula
being connected with the stem of a T-tube. One end of the horizontal limb
of the T-tube is connected with the tambour; the other is provided with a
rubber tube, which can be partially closed by a screw-clamp to regulate the
excursion. Ether may be given when required by connecting the horizontal
limb of the T-tube with a bottle with two glass tubes in the cork (p. 201).
PRACTICAL EXERCISES 301
(c) Apply a strong solution- of potassium chloride with a .camel's-
hair brush to the central end of the vagus while a tracing is being taken,
and observe the effect.
(d) Isolate the sciatic nerve (p. 212), ligature it, and cut below the
ligature. Stimulate its central end while a tracing is being taken.
The respiratory movements will be increased.
(e) Disconnect the cannula, and isolate the vagus on the other side.
While a tracing is being taken, divide it. The respiratory movements
will probably at once become deeper and less frequent.
(/) Again disconnect the cannula. Isolate the superior laryngeal
branch of the vagus. This will be found entering the larynx at the
point where the laryngeal horn of the hyoid bone is connected with the
thyroid cartilage. If the finger is passed back along the upper border
Fig. 135. — Arrangement for Respiratory Tracing. Two glass tubes are inserted
through a cork in the mouth of the large bottle. One of them has a small piece of
indiarubber tubing on it, which is closed or opened, as may be required, by a
screw-clamp. The other is connected by a rubber tube with a recording tambour.
The tubulure at the bottom of the bottle is closed by a cork, through which
passes a glass tube, connected by a rubber tube with the tracheal cannula. If
no bottle with tubulure is available, it is only necessary to pass through the cork,
down to the bottom of the bottle, a third glass tube, which is connected with the
tracheal cannula. While a tracing is being taken the animal breathes the air
contained in the bottle. When this becomes vitiated the respiratory movements
are exaggerated and a normal tracing is no longer obtained. For this reason
the tracheal cannula must be connected with the bottle only at the moment
when a tracing is to be taken. The arrangement is most suitable for a small
animal.
of the thyroid cartilage, this point will easily be felt. Ligature the
nerve, and divide it between the larynx and the ligature. Reconnect
the cannula. Take a tracing first with weak, and then with strong
stimulation of the central end of the superior laryngeal.
(g) Make an incision through the abdominal wall in the linea alba,
and study the movements of the diaphragm. Find the nerves from
which the phrenics take origin in the neck. In the dog they arise from
the fifth, sixth, and seventh cervical nerves. Divide the phrenic fibres
302
RESPIRA TION
on one side, and observe that the diaphragm on the corresponding side
is now paralyzed.
(h) Insert a cannula into the carotid artery. While a respiratory
tracing is being taken, allow blood to flow from the artery. Dyspnoea and
exaggeration of the respiratory movements will be seen when a consider-
able quantity of blood has been lost. Mark and varnish the tracings.
In the whole of this experiment the tracheal cannula is to be dis-
connected, except when the lever is actually writing on the drum, in
order that the period during which the animal must breathe into the
confined space of the bottle may be diminished as much as possible.
Instead of the method described, the stethograph shown in Fig. 136
may be used to obtain respiratory tracings from animals, a broad canvas
band being put round the animal's chest. To each end of this band is
clamped with sufficient tension a strong thread (F), fastened to a small
metal disc on the inside of the
rubber dam closing the obliquely-
cut ends of the metal cylinder D.
The tube G is connected with a
tambour or with a bellows recorder
(Fig. 13?)-
4. The Effect of Temperature on
tha Respiratory Centre— Heat Dysp-
noea.— Set up an arrangement for
Fig. 136.— Stethograph (Crile).
Fig. 137. — Bellows Recorder. B. a
lead tube connected with the
small bellows A, which consists of
a light wooden base and top. to
which is cemented very flexible
(organ key) leather, properly
creased for expansion and con-
traction; C, writing lever.
taking a respiratory tracing as in 2
(footnote, p. 300). Anaesthetize a
dog, and fasten it, back downward,
on a holder. Make an incision in
the middle line of the neck, com-
mencing a little below the cricoid
cartilage, and extending down for
4 or 5 inches. Insert a cannula into the trachea. Isolate both carotid
arteries for as great a distance as possible, and arrange them on the
brass tubes shown in Fig. 138. Connect two adjacent ends of the
tubes by a short rubber tube. Connect one of the remaining ends to a
funnel, supported on a stand, and the other to a rubber tube hanging
over the table above a large jar. Slip two or three folds of paper
between the tubes and the vagus nerves. Heat two or three litres of
water to about 65° C. (a) Now connect the tracheal cannula with the
tambour. As soon as the tracing is under way, let the hot water run
through the funnel and tubes into the jar. Mark on the tracing the
point at which the flow of the hot water was begun, and go on passing
it until it has produced an effect. Then stop the drum, and circulate
water at the ordinary temperature till the breathing is again normal.
Then, while a tracing is being taken, pass ice-cold water through the
tubes, and again notice the effect.
PRACTICAL EXERCISES
303
(6) Expose the sciatic. Pass ice-water through the tubes, and while
a respiratory tracing is being taken stimulate its central end with in-
duction shocks so weak as just to cause an effect. Pass water at air
temperature through the tubes, and repeat the stimulation with the
coils at the same distance. Do the same while hot water is being passed
through the tubes, and compare the results. Always allow the water
to pass for a time before making an observation.
5. Measurement of Volume of Air inspired or expired — Vital Capacity.
— A spirometer (Fig. 114, p. 235) of sufficient accuracy for this experi-
ment can be made by removing the bottom of a large bottle with a
capacity of not less than 4 litres. A good cork, through which passes
a glass tube connected with a rubber tube, is fitted into the neck. The
bottle is fixed vertically, mouth downwards, the glass tube being closed
for the time, and graduated, by pouring in measured quantities of water,
say 100 c.c. at a time, and marking the level. The divisions are then
etched in. If the cork does not fit air-tight, it is covered with wax.
The bottle is swung on two pulleys, counterpoised and immersed,
bottom down, in a large
glass jar or a small cask
nearly full of water. A
smaller bottle may be used
for the determination of the
tidal air, so as to reduce the
error of reading.
(i) Submerge the bottle
to the stopper, after opening Fig. 138.— Arrangement for Heating or Cooling
the Blood in the Carotid Arteries. A, cylin-
drical portion of tube; B, flattened portion in
the groove, between which and A the artery
lies; C, cross-section, showing the lumen extend-
ing into B; D, rubber tube attached to a brass
tube soldered into A. The other end of A has
a similar brass tube soldered into it (not shown
in the figure). This is connected by a rubber
tube with a similar apparatus, on which the
other carotid lies. D is connected with a funnel
containing hot or cold water or with the outflow
tube, as the case may be.
the pinchcock on the rub-
ber tube. Breathe into the
bottle, close the cock, ad-
just the bottle so that the
level of the water is the
same inside and outside, and
then read off the level. De-
termine the volume of air
expired in —
(a) A normal expiration
after a normal inspiration
(tidal air) ;
(b) The greatest possible expiration after a normal inspiration
(supplemental air plus tidal air) ;
(c) The greatest possible expiration after the greatest possible
inspiration (vital capacity).
(2) Open the cock and raise the bottle till it is nearly full of air.
Determine the volume of air inspired in —
(a) A normal inspiration after a normal expiration (tidal air) ;
(b) The greatest possible inspiration after a normal expiration
(complemental air plus tidal air) ;
(c)- The greatest possible inspiration after the greatest possible
expiration (vital capacity).
Make several observations of each quantity, and take the mean.
(3) Count the rate of respiration for three minutes, keeping the
breathing as nearly normal as possible; repeat the observation; and
from the mean result and the amount of the tidal air calculate the
quantity of air taken into the lungs in twenty-four hours (pulmonary
ventilation).
6. Cardio-Pneumatic Movements. — Fill a U-tube with tobacco-
smoke. One end of the tube is placed in the nostril of a fellow-student.
304 RESPIRA TION
and made tight with a little cotton-wool. The other nostril and the mouth
are closed, and respiration suspended. The column of smoke moves
in and out at each beat of the heart. By feeling the apex-beat, try to
verify the fact that during systole the cardio-pneumatic movement is
inspiratory, and in diastole expiratory.
7. Auscultation of the Lungs. — This is taught in the course of physical
diagnosis, but in connection with the subject the student may perform
the following experiment on a dog used for some other purpose : Open
the trachea as described on p. 201. Insert into it the cross-piece of a
glass T-tube of as large a bore as possible, tying the trachea over it on
each side of the stem. The stem projecting from the wound is armed
with a short piece of rubber tubing, which can be closed at will with a
clip. When the tube is thus closed the animal breathes through the
glottis in the ordinary way. When the tube is open, and the mouth
and nose covered tightly with a cloth, no air goes through the glottis.
The tube being closed, listen with the stethoscope or the ear alone over
a part of the chest where the vesicular murmur is well heard. If the
Fig. 139. — Haldane's Apparatus for measuring the Quantity of CO2 and Aqueous
Vapour given off by an Animal. A, chamber into which the animal is put;
i and 4, Woulff's bottles filled with soda-lime to absorb carbon dioxide; 2. 3, and
5, Woulflt's bottles filled with pumice-stone soaked in sulphuric acid to absorb
watery vapour; B, glass bell-jar suspended in water, by means of which the
negative pressure is known; P, water-pump which sucks air through the appar-
atus: i and 2 are simply for absorbing the carbon dioxide and water of the
ingoing air.
rubbing of the hairs below the stethoscope causes disturbing sounds,
shave a portion of the skin. Continue listening while an assistant
closes the tube and covers up the animal's muzzle. Determine whether
any change takes place in the vesicular sound.
Repeat the observation while listening over the lower part of the
trachea, and determine whether any change takes place in the bronchial
breathing sound.
8. Respiratory Pressure. — Connect a strong rubber tube with a glass
bulb, and the bulb with a mercurial manometer provided with a scale,
(i) Fasten the tube with a little cotton-wool in one nostril, breathe
through the other with closed mouth, and observe the amount by which
the level of the mercury is altered in ordinary inspiration and ex-
piraton.
(2) Repeat the observation with forced breathing, pinching the tube
at the height of inspiration and expiration, and reading off the maximum
inspiratory and expiratory pressure.
PRACTICAL EXERCISES ^
(3) Repeat (i) with the tube connected to the mouth by a glass
tube held between the lips, and the nostrils open.
(4) Repeat (2) with the tube in the mouth and the nostrils closed.
9. Estimation of the Quantity of Water and of Carbon Dioxide given
off by an Animal (Haldanes Method). — (i) Connect the apparatus
shown in Fig. 139 with the water-pump. Allow a negative pressure
of 5 or 6 inches of water to be established in it, as shown by the rise of
water in the bell-jar B. Then close the open tube of carbon dioxide
bottle i, and clamp the tube between the water-pump and the bell-jar.
If the negative pressure is maintained, the arrangement is air-tight.
Now weigh bottle 3 and bottles 4 and 5, the last two together. Place
a cat in the respiratory chamber A, connect the chamber directly with
the water-pump, and test whether it is tight. Then take the stopper
out of bottle i, and adjust the rate at which air is drawn through the
apparatus. Let the ventilation
go on for a few minutes, then
insert bottles 3, 4, and 5 again.
Note the time exactly at this
point, and after an hour dis-
connect 3, 4, and 5, and again
weigh. The difference of the
two weighings of 3 shows the
quantity of water given off by
the animal in an hour ; the dif-
ference in the combined weight
of 4 and 5, the quantity of
carbon dioxide . Weigh the cat ,
and calculate the amount of
water and of carbon dioxide
given off per kilo per hour.
(2) For the student it is
more convenient to use smaller
animals. The mouse may be
taken as an example of a
warm-blooded animal, and the
frog of a cold-blooded. Instead
of the Woulff 's bottles use wide
test - tubes connected as in
Fig. 140, and for the animal
chamber a small beaker, closed
with a very carefully fitted
cork which has been boiled in paraffin. The inlet and outlet tubes of
the chamber are to be introduced through this cork. The holes for these
are to be bored with the greatest care, and the tubes to be put in while
the cork is still hot from boiling in paraffin. Also insert a thermom-
eter about 6 inches long registering from o° C. to 45° C. Modeller's
wax is to be used finally to render all the junctions air-tight.
Add to the series of tubes described in the apparatus a single tube
jntaining baryta- water. This is placed to the left of tube 5, and so
arranged that the air-current bubbles through the water. As long
as the absorption of carbon dioxide is complete, the baryta-water
remains clear. Beyond this a water-bottle should be placed to act
as a valve and to indicate the negative pressure in the apparatus. It
can be most simply constructed by using a cylinder of stout glass
tubing in a wide-mouthed bottle containing some water, the inlet and
outlet tubes passing through a paraffined cork which seals the upper
end of the cylinder. 20
Fig. 140. — Absorption Tubes for CO2 and
Moisture. A, soda -lime tube; B, [sul-
phuric acid tube; C, wooden frame, in
which A and B are supported by wires d ;
>, wire hook, which grips the glass tube
firmly, and by means of which the tubes
are lifted out of the frame in order to be
weighed; a, short piece of glass tubing,
by taking out which the absorption tubes
are disconnected from the rest of the
apparatus; e, glass tube going off to animal
chamber.
3°8 RESPIRA T/O.V
Before making an observation, test whether the apparatus is air-
tight, as explained above, after introducing the animal into the cham-
ber, sealing the latter with wax, and connecting it with the absorption-
tubes. But a negative pressure of 2 or 3 inches of water is a sufficient
test for the small apparatus.
To make an observation, set the air-current going at the desired
rate. Allow it to run for a few minutes till the carbon dioxide, which
has accumulated during the testing, has been swept out. At a time
which has been decided on and noted, stop the current by disconnecting
the water-pump. Disconnect and stopper up the animal chamber, and
weigh it as quickly as possible. Connect up again, using only recently-
weighed absorption-tubes, and finally connect with the water-pump
and allow the current to pass for a definite period, say an hour.
The soda-lime should not be too dry, or absorption is not sufficiently
rapid. The following facts are made out: (a) Loss of weight by the
animal chamber (chiefly loss by the animal) ; (b) gain of the sulphuric
acid tube in water; (c) gain of the soda-lime tubes in carbon dioxide.
The total loss and total gain do not correspond, the gain being always
greater than the loss. The surplus can only be oxygen absorbed by the
animal and added to the hydrogen and carbon of its substance to form
water and carbon dioxide. Calculate the respiratory quotient (p. 241).
10. Muscular Contraction in the Absence of Free Oxygen (see p. 267).
— Pith a frog (brain and cord). Cut off one hind-leg at the middle
of the thigh, and strip the skin from it. Pass a thread under the tendo
Achillis, tie it, and divide the tendon below it. Free the tendon and
the gastrocnemius muscle from the loose connective tissue lying between
them and the bones of the leg, and divide the latter just below the knee.
Remove superfluous thigh muscles, and fasten the gastrocnemius in
a moist chamber by means of the femur. Attach the thread on the
tendon to a lever. Connect the poles of the secondary coil of an induc-
tion machine by fine copper wires to the femur and the tendon. Put
a battery and simple key in the primary, and arrange it for single shocks.
Stimulate the muscle and observe the height of the contraction. Now
pass into the chamber a current of washed hydrogen gas from a bottle
containing granulated zinc, upon which a little dilute sulphuric acid
is poured from time to time. The air in the moist chamber will soon
be entirely displaced by the hydrogen, but the muscle will contract on
being stimulated, and the stimulation can be repeated many times.
11. Oxidizing Ferments. — Wash out the bloodvessels of a dog or
rabbit (Practical Exercises, p. 65). Chop up finely portions of pancreas,
spleen, muscle, lungs, and kidney, keeping each separate, and avoiding
any contamination of one by another. Grind up half of each portion
with sand in a small mortar, and extract with a small quantity of water,
keeping all the extracts separate. Into each of eleven test-tubes put
10 c.c. of a colourless dilute alkaline solution of paraphenylenediamin
and a-naphthol (freshly made by mixing solutions of the two sub-
stances in equimolecular proportions* and adding a little sodium
carbonate). To five of the tubes add the chopped organs, to five the
watery extracts of the organs, and enough water to make the volume
equal in all the tubes. To the remaining tube add the same amount
of water. Observe in which tube a change of colour takes place (p. 272).
* I.e., the weight of each of the two substances in the mixture should be
proportional to its molecular weight. A convenient solution contains 0-144
per cent, of a-naphthol and o'io8 pei cent, of paraphenylenediamin. These
quantities are one-hundredth-molecular. Sod urn carbonate is added to the
amount of 0-25 per cent. The a-naphthol can be kept as a i per cent, solu-
tion in 50 per cent, alcohol.
CHAPTER V
VOICE AND SPEECH
Voice. — Sounds of various kinds are frequently produced by the
movements of animals as a whole, or of individual organs. The
muscular sound, the sounds of the heart and of respiration, we have
already had to speak of. Such sounds may be considered as purely
accidental as the footfall of a man or the buzzing of a fly. The
wings of an insect beat the air, not to cause sound, but to produce
motion; the respiratory murmur is a mere indication that air is
finding its way into the lungs, it is in no way related to the oxidation
of the blood in the pulmonary capillaries. But in many of the
higher animals mechanisms exist which are specially devoted to the
utterance of sounds as their prime and proper end. In man the
voice-producing mechanism consists of a triple series of tubes and
chambers : (i) The trachea, through which a blast of air is blown ;
(2) the larynx, with the vocal cords, by the vibrations of which
sound-waves are set up ; and (3) the upper resonance chambers, the
pharynx, mouth, and nasal cavities, in which the sounds produced
in the larynx are modified and intensified, and in which independent
notes and noises arise.
The larynx is a cartilaginous box, across which are stretched,
from front to back, two thin and sharp-edged membranes, the (true)
vocal cords. In front the cords are attached to the thyroid carti-
lage, one a little to each side of the middle line; behind they are
connected to the vocal or anterior processes of the pyramidal
arytenoid cartilages. The thyroid and the two arytenoids are
mounted upon a cartilaginous ring, the cricoid. The arytenoids
! can rotate on the cricoid about a vertical axis, while the cricoid can
rotate on the thyroid cartilage around a transverse horizontal axis.
The cricoid can thus be raised by the contraction of the crico-
thyroid muscle, and the vocal cords stretched. By the pull of the
posterior crico-arytenoid muscles, attached to the external or mus-
i cular processes of the arytenoid cartilages, the vocal processes are
rotated outwards, the cords separated from each other or abducted,
and the chink between them, the rima glottidis, widened. When
:i the vocal processes are approximated by contraction of the lateral
307
3oS VOICE AND SPEECH
crico-arytenoid muscles and the consequent forward movement of
the muscular processes, the vocal cords are brought close together,
or adducted, and the rima is narrowed. The transverse or posterior
arytenoid muscle, which connects the two arytenoid cartilages
behind, also helps, by its contraction, to narrow the glottis by shift-
ing the cartilages on their articular surfaces somewhat nearer the
middle line. Running in each vocal cord, and, in fact, incorporated
with its elastic tissue, is a muscle, the thyro-arytenoid, the external
portion of which may to some extent cause inward rotation of the
vocal processes and adduction of the cords ; but the main function,
at least of its inner part, is to alter the tension of the cords. The
diagrams in Figs. 141 and 142 illustrate the action of the abductors
and adductors of the vocal cords.
The crico-thyroid muscle and the deflectors of the epiglottis are
supplied by the superior laryngeal branch of the vagus, which also
Fig. 141. — Diagrammatic Hori-
zontal Section of Larynx to
show the Direction of Pull of
the Posterior Crico-Arytenoid
Muscles, which abduct the
Vocal Cords. Dotted lines
show position in abduction.
Fig. 142. — Direction of Pull- of
the Lateral Crico-Arytenoids,
which adduct the Vocal
Cords. Dotted lines show
position in adduction.
contains the sensory fibres for the mucous membrane of the larynx
above the vocal cords. In the dog 'and rabbit motor fibres also reach
the crico-thyroid by the so-called middle laryngeal nerve which
arises from the superior pharyngeal branch of the vagus. All the
other intrinsic muscles are supplied by the recurrent laryngeal
branch of the vagus. It receives these motor fibres from the spinal
accessory, and supplies sensory fibres to the mucous membrane of
the larynx below the vocal cords and to the trachea.
The voice is produced, like the sounds of a reed instrument, by
the rhythmical interruption of an expiratory blast of air by the
vibrating vocal cords. When a bell is struck, vibrations are set up
in the metal, which are communicated to the air. It is not the same
with the vibrations of the vocal cords; if they were plucked or
struck, they would only produce a feeble note. The air in the
mouth, pharynx, larynx, trachea, and lungs is the real sounding
VOICE 309
body ; a pulse of alternate rarefaction and condensation is set up in
it by the interference, at regular intervals, of the vocal cords with
the expiratory blast. Forced abruptly from their position of equi-
librium as the blast begins, they almost immediately regain and
pass below it, in virtue of their elasticity, and continue to vibrate as
long as the stream of air continues to issue in sufficient strength.
Not only do they vibrate up and down, but also towards and away
from the middle line, so that, at least in the chest voice, they come
into contact with each other at each swing. The sound-waves thus
set up spread out on every side, impinge on the tympanic membrane,
set it quivering in response, and give rise to the sensation of sound.
We may say, in a word, that the whole exquisite mechanism of
cartilages, ligaments, and muscles, has for its object the production
of a sufficient pressure in the blast of air driven through the wind-
pipe by an expiratory act, and of a suitable tension in the vibrating
cords. An approximation of the cords, a narrowing of the glottis,
is essential to the production of voice; with a widely-opened glottis
the air escapes too easily, and the necessary pressure cannot be
attained. The pressure in the windpipe was found in a woman
with a tracheal fistula to be about 12 mm. of mercury for a note of
medium height, about 15 mm. for a high note, and about 72 mm.
for the highest possible note. The period of vibration of structures
like the vocal cords depends on their length, thickness, density and
tension ; the shorter, thinner, more dense and less tense a stretched
string is, the greater is the vibration frequency, the higher the note.
In the child the cords are short (6 to 8 mm.), in woman longer
(10 to 12 mm. when slack, 13 to 15 mm. when stretched), in man
longest of all (14 to 18 mm. in the relaxed, and 18 to 22 mm. in the
stretched position) ; and the lower limit of the voice is fixed by the
maximum length of the relaxed cords. A boy or a woman cannot
utter a deep bass note, because their vocal cords are relatively
short, and do not vibrate with sufficient slowness. It is true that
by the action of the crico-thyroid muscle the cords can be length-
ened, and that the maximum length in a woman approaches or
exceeds the minimum length in a man. But the lengthening of the
vocal cords in one and the same individual is always accompanied
by other changes — increase of tension, decrease of breadth and
thickness — which tell upon the vibration frequency in the opposite
way, and more than compensate the effect of the increase of length,
so that for high notes the cords are longer than for low. The con-
traction of the thyro-arytenoid muscle is a more influential factor
in altering the tension of the cords than the contraction of the crico-
thyroid. It is probable that, when the highest notes are uttered,
only the anterior portions of the cords are free to vibrate, their
posterior portions being damped by the approximation of the vocal
processes of the arytenoid cartilages by the contraction of the
3io VOICE AND SPEECH
lateral crico-arytenoid and transverse arytenoid muscles. The
range of an ordinary voice is 2 octaves; by training z\ octaves can
be reached; but in exceptional cases a range of 3, and even 3^,
octaves (as in the celebrated singer Catalini) has been known.
The development of the voice in children is of great interest. At
the age of six years the boy's voice has a rather narrower range than
the girl's in both directions. The boy's voice reaches its full height
in the twelfth and its full depth in the thirteenth year, when the range
is almost 3 octaves, its upper limit being a semitone higher than the
girl's, but its lower limit a whole tone deeper. When the voice ' breaks '
in boys at the age of puberty it falls about an octave. The control of
the vocal organs becomes so incomplete that only in one-fourth of the
cases can notes of sufficient steadiness to be used in music be produced.
The vocal cords, as may be seen with the laryngoscope, are frequently,
though not always, congested.
The pitch of a note, while it depends chiefly, as has been said, on
the tension of the vocal cords, rises and falls somewhat with the
strength of the expiratory blast ; the highest notes are only reached
with a strong expiratory effort. The intensity of all vocal sounds
is determined by the strength of the blast, for the amplitude of
vibration of the cords is proportional to this. Besides pitch and
intensity, the ear can still distinguish the quality or timbre of sounds ;
and the explanation is as follows: Two simple tones of the same
pitch and intensity, that is, the sounds caused by two series of air-
waves of the same period and amplitude — of the same frequency
and height, to use less technical terms — would appear absolutely
identical to the sense of hearing; just as the aerial disturbances on
which they depend would be absolutely alike to any physical test
that could be applied. But no musical instrument ever produces
sound-waves of one definite period, and one only; and the same is
true of the voice. When a stretched string is displaced in any way
from its position of rest, it is set into vibration; and not only does
the string vibrate as a whole, but portions of it vibrate independently
and give out separate tones. The tone corresponding to the vibra-
tion period of the whole string is the lowest of all. It is also the
loudest, for it is more difficult to set up quick than slow vibrations.
The ear therefore picks it out from all the rest ; and the pitch of the
compound note is taken to be the pitch of this, its fundamental
tone. The others are called partial or overtones, or harmonics of
the fundamental tone, their vibration frequency being twice, three
times, four times, etc., that of the latter. Now, the fundamental
tone of a compound note or clang produced by two musical instru-
ments may be the same, while the number, period, and intensity
of the harmonics are different ; and this difference the ear recognizes
as a difference of timbre or quality. The timbre of the voice de-
pends for the most part on partial tones produced or intensified in
the upper resonance chambers.
VOICE 3"
A great deal of our knowledge as to the mode and mechanism of
the production of voice has been acquired by means of the laryngo-
scope (Fig. 143)- This consists of a small plane mirror mounted on
a handle, which is held at the back of the mouth in such a position
that a beam of light, reflected from a larger concave mirror fastened
Dn the forehead of the observer, is thrown into the larynx of the
patient. The observer looks through a hole in the centre of the
large mirror; and an image of the interior of the larynx is seen in
the small mirror, in which the parts that are anterior appear as
posterior, the arytenoid cartilages in front, the thyroid behind, and
the vocal cords stretching between. The small mirror is warmed to
body-temperature before being introduced, so as to prevent the
condensation of moisture on it. The tendency to retch, which is
Concave Mirror
Larynx.
Fig. 143. — Diagram of Laryngoscope.
caused by contact of the instrument with the soft palate, may be
removed or lessened by the application of a solution of cocaine.
Examined with the laryngoscope during quiet respiration, the
glottis is seen to be moderately, though not widely, open, and the
vocal cords almost motionless. Although the portion between the
arytenoid cartilages has received the name of glottis respiratoria, in
contradistinction to the glottis vocalis between the vocal cords, the
rima in its whole extent from front to back is really concerned in
the respiratory act. In deep expiration the vocal cords come nearer
to the middle line, and the glottis is narrowed ; in deep inspiration
they are widely separated, and the rings of the trachea, and even
its bifurcation, may be disclosed to view. When a sound is produced
a note sung, for example — the cords are approximated (Figs. 144
d 145) ; and with a high note more than with a low-
312
VOICE AND SPEECH
The essential difference between the production of notes in the lower
register, or chest voice, and in the higher register, or falsetto, has been
much debated. The lowest notes which can be uttered by any given
voice are chest notes, the highest are falsetto notes; but there is a de-
batable land common to both registers, and medium notes can be sung
either from the chest or from the head. Chest notes impart a vibration
or fremitus to the thoracic walls, from the resonance of the lower air-
chambers, the trachea and bronchi; and this can be distinctly felt by
the hand. In head notes or falsetto the resonance is chiefly in the
upper cavities, the pharynx, mouth, and nose. As to the mechanical
conditions in the larynx, there is a pretty general agreement that during
the production of falsetto notes the vocal cords are less closely approxi-
mated than in the sounding of chest notes. The escape of air is conse-
quently more rapid in the head voice, and a falsetto note cannot be
maintained so long as a note sung from the chest. But it is only the
anterior part of the rima glpttidis that is wider in the falsetto voice ;
the whole of the glottis respiratoria, and even the posterior portion of
the glottis vocalis, are closed during the emission of falsetto notes.
Fig. 144. — Position of the
Glottis preliminary to the
Utterance of Sound, rs, false
vocal cord; vi, true vocal
cord; ar, arytenoid cartilage;
b, pad of the epiglottis.
fi
Fig. 145. — Position of Open Glottis.
I, tongue; e, epiglottis; ae, ary-
epiglottidean fold; c, cartilage of
Wrisberg; ar, arytenoid cartilage;
o, glottis; v, ventricle of Mor-
gagni; tit true vocal cord; ts, false
vocal cord.
Oertel has stated, and the statement has been confirmed by others,
that the free edge of the vocal cord alone vibrates in the falsetto voice,
one or more nodes or motionless lines parallel to the edge being formed
by the contraction of the internal part of the thyro-arytenoid muscle,
which thus acts like a stop upon the cord.
Approximation of the vocal cords may take place in certain
acts unconnected with the production of voice. Thus, a cough, as
has already been mentioned, is initiated by closure of the glottis.
During a strong muscular effort, too, the chink of the glottis is
obliterated, and respiration and phonation both arrested. The
object of this is to fix the thorax, and so afford points of support
for the action of the muscles of the limbs and abdomen. But con-
siderable efforts can be made even by persons with a tracheal fistula.
Speech. — Ordinary speech is articulated voice — voice shaped and
fashioned by the resonance of the upper air-cavities, and jointed
SPEECH
313
together by the sounds or noises to which the varying form of these
cavities gives rise. Here we come upon the fundamental distinction
between vowels and consonants. Vowels are musical sounds; con-
sonants are not musical sounds, but noises — that is to say, they are
due to irregular vibrations, not to regularly recurring waves, the
frequency of which the ear can appreciate as a definite pitch. This
difference of character corresponds to a difference of origin: the
vowels are produced by the vibrations of the vocal cords; the con-
sonants are due to the rushing of the expiratory blast through
certain constricted portions of the buccal chamber, where a kind of
temporary glottis is established by the approximation of its walls.
One of these ' positions of articulation ' is the orifice of the lips; the
consonants formed there, such as p and b, are called labials. A
second articulation position is between the anterior part of the
tongue and the teeth and hard palate. Here are formed the dentals,
t, d, etc. The ordinary English r, and the r of the Berwickshire and
East Prussian ' burr,' also arise in this position through a vibratory
motion of the point of the tongue. The third position of articulr.-
tion is the narrow strait formed between the posterior portion of th :
arched tongue and the soft palate. To the consonants arising here
the name of gutturals has been given. They include k, g, the
Scottish ch, and the uvular German r. The latter is produced by
a vibration of the uvula. The aspirated h is a noise set up by the
air rushing through a moderately wide glottis, and some have there-
fore included the glottis as a fourth articulation position for con-
sonants. Certain sounds like n, m, and ng, when final (as in pen,
dam, ring), although produced at the glottis, are intensified by the
resonance of the air in the nose and pharynx, and are sometimes
spoken of as nasal consonants.
As we have said, the vowels are produced by vibrations of the
vocal cords, but to what they owe their special timbre or quality has
been much discussed. According to the view with which Helm-
holtz's name is particularly connected this is due to the reinforce-
ment of certain overtones by the resonating cavities, the shape and
fundamental tone of which are different for each vowel.
When a vowel is whispered, the mouth assumes a characteristic
shape, and emits the fundamental tone proper to the form and size
of the particular ' vowel-cavity,' not as a reinforcement of a tone set
up by the vibrations of the vocal cords, but in response to the rush of
air through the cavity; just as a bpttle of given shape and size gives out
a definite note when the air which it contains is set in vibration, by
blowing across its mouth. A whisper, in fact, is speech without voice ;
the larynx takes scarcely any part in the production of the soifiid ; the
vocal cords remain apart and comparatively slack ; and the expiratory
blast rushes through without setting them in vibration.
The fundamental tone of the ' vowel-cavity ' may be found for each
vowel by placing the mouth in the position necessary for uttering it,
then bringing tuning-forks of different period in front of it, and noting
VOICE AND SPEECH
which of them sets up sympathetic resonance in the air of the mouth,
and so causes its sound to be intensified. The. fundamental tone is
lowest for u (as in lute). Next comes o ; then a (as in path] ; then a (as
in fane) ; then i ; while e is highest of all. A simple illustration of
this may be found in the fact that when the vowels are whispered in
the order given, the pitch rises. When u or o is sounded, the buccal
cavity has the form of a wide-bellied flask, with a short and narrow neck
for u, a still shorter but wider neck for o. For e the tongue is raised
and almost in contact with the palate, and the cavity of the mouth
is shaped like a flask with a long narrow neck and a very short belly.
For i the shape is similar, but the neck is not so narrow. For a (as in
path] the vowel-cavity is intermediate in form between that of u and e,
being roughly funnel-shaped, and the mouth is rather widely opened.
For u (oo) the resonating cavity is made as long as possible, the larynx
being depressed and the lips protruded; for e the resonating cavitj is
at its shortest, the larynx being raised as much as possible and the lips
retracted (Figs. 146 to 148).
According to Helmholtz, all that the resonating cavity does is to
strengthen certain of the partials or overtones of the laryngeal note.
ou
Fig. 146.
Fig. 147.
Fig. 148.
If this is true, the partials which give a vowel-sound the timbre by
which we recognize it as different from other vowel-sounds cannot
preserve the same numerical relation to the fundamental tone when
the pitch of the latter is altered. Suppose, for example, that a given
vowel is sounded with a pitch corresponding to 100 vibrations a second,
and that the partial which is particularly strengthened by the resonance
of the mouth cavity is the fifth overtone, corresponding to 600 vibra-
tions. Then when the same vowel is sounded with a pitch of 200 vibra-
tions, the reinforced partial which will now give the quality to the sound
will still correspond to 600 vibrations a second, since this is the rate
which most easily elicits the resonance, but it will not now be the fifth
but the second overtone.
Universally accepted for a time, the Helmholtz theory has been in
recent years assailed, especially by Hermann, who bases his criticism
on microscopic examination of curves obtained by the Edison phono-
graph, and on reproductions of such records obtained by photographing
on a moving drum covered with sensitive paper a beam of light re-
flected from a small mirror attached to a system of levers whose move-
ments follow the curves faithfully and greatly magnify them. Hermann
SPEECH
315
has come to the conclusion that the mouth does not act as a mere
resonator, but that for each vowel, in addition to the fundamental
note due to the vibration of the vocal cords, the pitch of which is, of
course, variable, one or, it may be, two other notes (formants, as he
calls them), not necessarily harmonics of the laryngeal note, but separ-
ated from it by a constant or nearly constant musical interval, are
directly produced by the passage of the regularly interrupted expiratory
blast through the mouth, the air contained in that cavity being for
an instant set into vibration at each interruption. On this view it
is the musical effect produced by the oscillation or continual recurrence,
in short series, of these vibrations which gives the vowels their quality.
The fact that it is by no means difficult to sing (with the larynx) and
whistle (with the mouth) at the same time, shows the possibility of
Hermann's view, that a fixed tone can be generated in the mouth by
the intermittent stream of air issuing from between the vibrating vocal
cords, just as a tone is generated in a pipe by blowing into or over it,
and his records do show continually recurring groups of vibrations as
his theory requires. McKendrick takes up a middle position, believing
that both theories are partially true, and this seems to be the best
conclusion which can at present be arrived at. It seems clear, at any
rate, that more than one factor is concerned in the timbre of the vowel
sounds.
When the vowels are being uttered, the soft palate closes the
entrance to the nasal chambers completely, as may be shown by
holding a candle in front of the nose, or trying to inject water
through the nares. If the cavities of the nose are not completely
blocked off, the voice assumes a nasal character in pronouncing
certain of the vowels; and in some languages this is the ordinary
and correct pronunciation.
Many animals have the power of emitting articulated sounds; a
few have risen, like man, to the dignity of sentences, but these only
by imitation of the human voice. Both vowels and consonants can
be distinguished in the notes of birds, the vocal powers of which
are in general higher than those of mammalian animals. The latter,
as a rule, produce only vowels, though some are able to form con-
sonants too.
The nervous mechanism of voice and speech will have to be
again considered when we come to study the physiology of the brain
and spinal cord. But the curious physiological antithesis between
the functions of abduction and of adduction of the vocal cords may
be mentioned here. The abductor muscles are not employed in the
production of voice; they are associated with the less specialized,
the less skilled and purposive function of respiration. The adductor
muscles are not brought into action in respiration; they are asso-
ciated with the highly specialized function of speech. Correspond-
ing to this difference of function, we find that adduction is pre-
ponderatingly represented in the cortex of the brain, abduction in
the medulla oblongata. Stimulation of an area in the lower part
of the ascending frontal convolution, near the fissure of Rolando, in
the macaque monkey, causes adduction of the vocal cords, never
3*6 VOICE AN'D SPEECH
abduction. In the eat, however, abduction of the cords may also
be obtained by stimulation of the cortex. The same is true of the
dog, but only when the peripheral adductor nerves have been
divided. Stimulation of the medulla oblongata (accessory nucleus)
causes abduction, never adduction. The skilled adductor function
is, therefore, placed under control of the cortex. The vitally im-
portant, but more mechanical, abductor function is governed by
the medulla. The abductor movements are more likely to be
affected by organic disease, the adductor movements by functional
changes. But the distinction between the two groups of muscles
is not entirely due to a difference of central connections, since by
altering the strength of the stimulus and the external conditions
the one or the other may be separately excited through the inferior
laryngeal nerve. Thus, strong stimulation of the inferior laryngeal
causes closure of the glottis, for although it supplies both abductors
III
Fig. 149. — Diagram of Vocal Cords in Paralyses of the Larynx, a, Paralysis of both
inferior laryngeal nerves. The vocal cords have taken up the ' mean ' position.
b. Paralysis of right inferior laryngeal nerve. An attempt is being made to
narrow the glottis for the utterance of sound. The right cord remains in its
5 mean ' position, 'c. Paralysis of the abductor muscles only, on both sides. The
cords are approximated beyond the ' mean ' position by the action of the
adductors.
and adductors, the latter, as the stronger muscles, prevail. With
weak stimulation, and in young animals, the abductors, owing to
the greater excitability of the neuro-muscular apparatus, carry off
the victory, and the glottis is opened (Russell).
When the nerve is cooled the abductors give way before the
adductor;. The same is true when it is allowed to become dry.
And after death in a cholera patient it was observed that the pos-
terior cric.o-arytenoid, an abductor muscle, was the first of the
intrinsic laryngeal muscles to lose its excitability. Lesions of the
medulla oblongata are often accompanied by marked changes in
the character of the voice and the power of articulation.
Section or paralysis of the superior laryngeal nerve causes the
voice to become hoarse, and renders the sounding of high notes an
impossibility, owing to the want of power to make the vocal cords
tense. Stimulation of the vagus within the skull causes contraction
SPEECH ^17
of the crico-thyroid muscle and increased tension of the cords. Sec-
tion or paralysis of the inferior laryngeal nerves leads to loss of voice
or aphonia, and dyspnoea (Fig. 149). Both adductor and abductor
muscles are paralyzed ; the vocal cords assume their mean position —
the position they have in the dead body — -and the glottis can neither
be narrowed to allow of the production of a note, nor widened during
inspiration. It is said, however, that young animals, in which the
structures around the glottis are more yielding than in adults, can
still utter shrill cries after section of the inferior laryngeals, the
contraction of the crico-thyroid muscle alone being able, while in-
creasing the tension of the cords, to draw them together.
Interference with the connections on one side between the higher
cerebral centres and the medulla oblongata, as by rupture of an
artery and effusion of blood into the posterior portion of the internal
capsule (giving rise to hemiplegia, or paralysis of the opposite side
of the body), is not followed by loss of voice; the laryngeal muscles
on both sides are still able to act.
CHAPTER VI
DIGESTION
IN the last chapter we have described the manner in which the
interchange of gases between the tissues and the air is carried out.
We have now to consider the digestion and absorption of the solid
and liquid food, its further fate in relation to the chemical changes
or metabolism of the tissues, and finally the excretion of the waste
products by other channels than the lung.
Logically, we ought to take metabolism after absorption and
before excretion, tracing the food through all its vicissitudes from the
moment when it enters the blood or lymph till it is cast out as useless
matter by the various excretory organs. Unfortunately, however,
many of the intermediate steps of the process are as yet hidden from
us ; we know best the beginning and the end. We can follow the food
from the time it enters the alimentary canal till it is taken up by the
tissues of absorption; and we have really a fair knowledge of this
part of its course. We can collect the end-products as they escape
in the urine, or in the breath, or in the sweat; and our knowledge of
them and of the manner in which they are excreted is considerable.
But of the wonderful pathway by which the dead molecules of the
food mount up into life, and then descend again into death, we
catch only a glimpse here and there. Only the introduction and
the conclusion of the story of metabolism are at present in our
possession in fairly continuous and legible form. We will read these
before we try to decipher the handful of torn leaves which represents
the rest.
SECTION I. — PRELIMINARY ANATOMICAL AND CHEMICAL DATA.
Comparative. — In the lowest kinds of animals, such as the amoeba,
there is neither mouth, nor alimentary canal, nor anus: the food,
wrapped round by pseudopodia, is taken in at any part of the animal
with which it happens to come in contact. A vacuole is formed around
it. Acid is secreted into the vacuole, the food is digested within the
cell-substance, and the part of it which is useless for nutrition is cast
out again at any part of the surface.
Coming a little higher, we find in the Coalenterates a mouth and
alimentary tube, which opens into the body-cavity, where a certain
PRELIMINARY ANATOMICAL AND CHEMICAL DATA 319
amount of digestion seems to take place, and from which the food is
absorbed either through the cells of the endoderm, or, as in Medusa,
by means of fine canals, which radiate from the body-cavity into its
walls, and form part of the so-called gastro-vascular system. In the
Echinodermata we have a further development, a complete alimentary
canal with mouth and anus, and entirely shut off from the body-cavity.
In many Arthropods it is possible already to distinguish parts corre-
sponding to the stomach, and the small and large intestines of higher
forms, the digestive glands being represented by organs which in some
groups seem to be homologous with the liver, and in others with the
salivary glands of the higher Vertebrates. A few Molluscs seem in
addition to possess a pancreas.
Among Vertebrates fishes have the simplest, and birds and mammals
the most complicated, alimentary system. In the lowest fishes the
stomach is only indicated by a slight widening of the anterior part of
the digestive tube. In water-living Vertebrates there are no salivary
glands. In birds the oesophagus is generally dilated to form a crop,
from which the food passes into a stomach consisting of two parts,
one pre-eminently glandular (proventriculus), the other pre-eminently
muscular (ventriculus). Among mammals a twofold division of the
stomach is distinctly indicated in rodents and cetaceae, but this organ
reaches its greatest complexity in ruminants, which possess no fewer
than four gastric pouches. The differentiation of the intestine into
small and large intestine and rectum is more distinct, both anatomically
and functionally, in mammals than in lower forms ; but there are marked
differences between the various mammalian groups both in the relative
size of the several parts of the digestive tube, and in the proportion
between the total length of the alimentary canal and the length of the
body. In general, the canal is longest in herbivora, shortest in carni-
vora. Thus, the ratio between length of body and length of intestine
is in the cat I : 4, dog i : 6, man I : 5 or 6, horse i : 12, cow i : 20, sheep
i : 27. The relative capacity of the stomach, small intestine, and large
intestine, is in the dog 6:2: 1-5, in the horse i : 3-5 : 7, in the cow
7:2:1. The area of the mucous surface of the alimentary canal is
very considerable, in the dog more than half that of the skin, the
surface of the small intestine being three times that of the stomach
and four times that of the large intestine. In the horse the mucous
surface has twice the area of the skin.
Anatomy of the Alimentary Canal in Man. — The alimentary canal
is a muscular tube, which, beginning at the mouth, runs under the
various names of pharynx, oesophagus, stomach, small intestine, large
intestine, and rectum, till it ends at the anus. Its walls are largely
composed of muscular fibres; its lumen is clad with epithelium, and
into it open the ducts of glands, which, morphologically speaking, are
involutions or diverticula formed in its course. In virtue of its muscular
fibres it is a contractile tube; in virtue of its epithelial lining and its
special glands it is a secreting tube ; in virtue of both it is fitted to per-
form those mechanical and chemical actions upon the food which
are necessary for digestion. Its inner surface is in most parts richly
supplied with bloodvessels, and in special regions beset with peculiarly-
arranged lymphatics; by both of these channels the alimentary tube
performs its function of absorption. From the beginning of the osso-
phagus to the end of the rectum the muscular wall consists, broadly
speaking, of an outer coat of longitudinally -arranged fibres, and a
thicker inner coat of fibres running circularly or transversely around
the tube. Between the layers lies a plexus of non-medullated nerves
and nerve-cells (Auerbach's plexus). In the stomach the longitudinal
32* DIGESTION
fibres are found only on the two curvatures, and a third incomplete
coat of oblique fibres makes its appearance internal to the circular
layer. In the large intestine, again, the longitudinal fibres are chiefly
collected into three isolated strands. In the pharynx the typical
arrangement is departed from, inasmuch as there is no regular longi-
tudinal layer; but the three constrictor muscles represent to a certain
extent the great circular coat. The muscles of the mouth and of the
pharynx are of the striped variety. So is the muscle of the upper half
of the oesophagus in man and the cat, and of the whole oesophagus
in the dog and the rabbit. In the rest of the alimentary canal the
muscle is smooth, except at the very end, where the external sphincter
of the anus is striped. In certain situations the circular coat is de-
veloped into a regular anatomical sphincter, a definite muscular ring,
whose function it is to shut one part of the tube off from another
(sphincter pylori, ileo-colic sphincter), or to help to close the external
opening of the tube (internal sphincter of anus). Elsewhere a tonic
contraction of a portion of the circular coat, not anatomically de-
veloped beyond the rest, creates a functional sphincter (cardiac sphincter
of stomach).
Throughout the greater part of the digestive tract the peritoneum
forms a thin serous layer, external to the muscular coat. Internally
the muscular coat is separated from the mucous membrane, the lining
of the canal, by some loose areolar tissue containing bloodvessels,
lymphatics, and nerves (Meissner's plexus), and called the submucous
coat. Between the mucous and submucous layers, but belonging to
the former, in the whole canal below the beginning of the oesophagus,
is a thin coat of smooth muscular fibres, the muscularis mucosae, con-
sisting in some parts, e.g., in the stomach, of two, or even three,
layers. Between this and the lumen of the canal lie the ducts and
alveoli of glands, surrounded by bloodvessels and embedded in adenoid
or lymphoid tissue, which in particular regions is collected into well-
defined masses (solitary follicles, Peyer's patches, tonsils), extending,
it may be, into the submucous tissue. In the mouth, pharynx, and
oesophagus, the glands lie in the submucosa, as do the glands of Brunner
in the duodenum; everywhere else they are confined to the mucous
membrane proper. Between the openings of the glands the mucous
membrane is lined with a single layer of columnar epithelial cells, some-
times (in the small intestine) arranged along the sides of tiny projec-
tions or villi. When the intestine is contracted the villi are long and
cylindrical in shape, when it is relaxed or distended they are flat and
conical. At the ends of the alimentary canal, viz., in the mouth,
pharynx, and oesophagus, and at the anus, the epithelium is stratified
squamous, and not columnar.
The purpose of food is to supply the waste of the tissues, to
replenish the stores of material from the oxidation of which the
energy required for the running of the bodily machine is derived,
and thus to maintain the normal composition of the body. In the
body we find a multitude of substances marked off from each other,
some by the sharpest chemical differences, others by characters
much less distinct, but falling upon the whole into the few fairly
definite groups already described (p. i).
Now, although it is by no means necessary that a substance in
the body belonging to one of these great groups should be derived
from a substance of the same group in the food, it has been found
PRELIMINARY ANATOMICAL AND CHEMICAL DATA 321
that upon the whole no diet is sufficient for man unless it contains
representatives of all; a proper diet must include proteins, carbo-
hydrates, fats, inorganic salts, and water. These proximate prin-
ciples have to be obtained from the raw material of the foodstuffs —
that is, as regards the first three groups, which can alone yield
energy in the body, from the tissues and juices of other living things,
plants or animals; it is the business of digestion to sift them out and
to prepare them for absorption. This preparation is partly mechan-
ical, partly chemical.
The water and salts and some carbo-hydrates, such as dextrose,
are ready for absorption without change. Fats are split into
glycerin and fatty acids before absorption. Indiffusible colloidal
carbo-hydrates, like starch and dextrin, are changed into diffusible
and readily soluble sugars, and the natural proteins into diffusible
peptones, and eventually into much simpler decomposition products.
These changes are obviously favourable to absorption. But this is
not their whole significance. For disaccharides, such as cane-sugar,
maltose, or lactose, although easily soluble in the contents of the
gut, and in themselves perfectly capable of being absorbed without
change, are, unless present in unusually large amount, all converted
into monosaccharides, such as dextrose, levulose, or galactose, either
in the lumen or in the wall of the alimentary tube. The reason is
that the disaccharides are unsuitable as pabulum for the cells.
Digestion is not only a preparation of the food for absorption by
the gut, but for assimilation by the tissues after absorption. An
equally important instance of this double function is seen in the
digestion of proteins. The complete shattering of the protein mole-
cule into amino-acids and the other groups yielded by its decom-
position (p. 360) is required, in the case of that portion of the protein
which goes to build up the tissues, because of the high degree of
specificity of the tissue proteins. The myosinogen of beef cannot
be cobbled into the myosinogen of human muscle, still less we may
suppose into the serum-albumin of human blood. It is necessary
that the food protein should be completely ' wrecked ' in digestion
so that protein which is to take its place in protoplasm may be built
exactly to order from the bricks. A satisfactory ' fit ' cannot be
obtained with ready-made protein. Mechanical division of the food
is an important aid to the chemical action of the digestive juices. We
shall see that this mechanical division forms a great part of the work
of the stomach, but it is normally begun in the mouth, and it is of
consequence that this preliminary stage should be properly performed.
SECTION II. — THE MECHANICAL PHENOMENA OF DIGESTION.
Mastication. — -It is among the mammalia that regular mastication
of the food first makes its appearance as an important aid to diges-
tion. The amphibian bolts its fly, the bird its grain, and the fish
322 DIGESTION
its brother, without the ceremony of chewing. In ruminating
mammals we see mastication carried to its highest point ; the teeth
work all day long, and most of them are specially adapted for
grinding the food. The carnivora spend but a short time in masti-
cation; their teeth are in general adapted rather for tearing and
cutting than for grinding. Where the diet is partly animal and
partly vegetable, as in man, the teeth are fitted for all kinds of work ;
and the process of mastication is in general neither so long as in the
purely vegetable feeders, nor so short as in the carnivora.
In man there are two sets of teeth: the temporary or milk teeth,
and the permanent teeth. The milk teeth are twenty in number,
and consist on each side of four incisors or cutting-teeth, two
canines or tearing-teeth, and four molars or grinding-teeth. The
central incisors emerge at the seventh month from birth, the other
incisors at the ninth month, the canines at the eighteenth, and the
molars at the twelfth and twenty-fourth month respectively.
Each tooth in the lower jaw appears a little before the corresponding
one in the upper jaw. Each of the milk teeth is in course of time
replaced by a permanent tooth, and in addition the vacant portion
of the gums behind the milk set is now filled up by twelve teeth,
six on each side, three above and three below. These twelve are
the permanent molars; they raise the number of the permanent
teeth to thirty-two. The permanent teeth which occupy the
position of the milk molars now receive the name of premolars.
The first tooth of the permanent set (the first true molar) appears
at the age of 6£ years; the last molar, or wisdom-tooth, does not
emerge till the seventeenth to the twenty-fifth year.
In mastication the lower jaw is moved up and down, so as to
alternately separate and approximate the two rows of teeth. It has
also a certain amount of movement from side to side, and from front
to back. The masseter, temporal and internal pterygoid muscles
raise, and the digastric, with the assistance of the mylo- and genio-
hyoid, depresses, the lower jaw, but its downward movement is
mainly a passive one. The external pterygoids pull it forward
when both contract, forward and to one side when only one con-
tracts. The lower fibres of the temporal muscle retract the jaw.
The buccinator and orbicularis oris muscles prevent the food from
passing between the teeth and the cheeks and lips. The tongue
keeps the food in motion, works it up with the saliva, and finally
gathers it into a bolus ready for deglutition.
Deglutition. — This act consists of a voluntary and an involun-
tary stage. Just before the beginning of the voluntary stage
mastication is suspended, and a slight contraction of the dia-
phragm generally takes place. The anterior part of the tongue
is suddenly elevated and pressed against the hard palate, and the
elevation travels back from the tip towards the root, as the mylo-
THE MECHANICAL PHENOMENA OF DIGESTION 323
hyoid muscles in the floor of the mouth contract sharply so as to
thrust the bolus through the isthmus of the fauces. As soon as this
has happened, and the food has reached the posterior portion of the
tongue, it has passed beyond the control of the will, and the second
or involuntary stage of the process begins.
This stage may be divided into two parts: (i) Pharyngeal,
(2) oesophageal — both being reflex acts. During the first the food
has to pass through the pharynx, the upper portion of which forms
a part of the respiratory tract, and is in free communication with
the larynx during ordinary breathing. It is therefore necessary
that respiration should be interrupted and the larynx closed while
the food is being moved through the pharynx. But that the inter-
ruption may be short, the food must be rapidly passed over this
perilous portion of its descent. The main propelling force under
which the bolus is shot through the back of the pharynx is derived
from the contraction of the mylo-hyoid muscles already mentioned,
assisted to some extent by the stylo- and palato-glossi ; and that
none of the purchase may be lost, the pharyngeal cavity is cut off
from the nose and mouth as soon as the bolus has entered it. The
soft palate is raised by the levator palati and palato-pharyngei
muscles; at the same time the upper part of the pharynx, narrowed
by the contraction of the superior constrictor, comes forward to
meet the soft palate, closes in upon it, and so prevents the food
from passing into the nasal cavities. The pharynx is cut off from
the mouth by the closure of the fauces through the contraction of
the palato-pharyngeal muscles which lie in their posterior pillars.
The upper free end of the epiglottis (the so-called pharyngeal part)
aids the back of the tongue in completing a movable partition across
the pharynx, which keeps close to the bolus as it passes down
between the posterior surface of the epiglottis and the posterior
wall of the pharynx. Almost immediately after the contraction
of the mylo-hyoids the larynx is pulled upwards and forwards by
the contraction of the thyro-hyoid muscle, and the elevation of the
hyoid bone by the muscles which connect it to the lower jaw.
The base of the tongue is simultaneously drawn backwards by the
stylo- and palato-glossus. The lower or laryngeal portion of the
epiglottis is thus caused to come into contact with the upper orifice
of the larynx, occluding it completely, but the pharyngeal portion
projects beyond the larynx, and takes no share in its closure
(Eykman). The glottis is closed by the approximation of the vocal
cords and the arytenoid cartilages. The epiglottis, however, is not
absolutely indispensable for closing the larynx, since swallowing
proceeds in the ordinary way when it is absent. The morsel of
food, grasped by the middle and lower constrictors as it leaves the
back of the tongue, passes rapidly and safely over the closed larynx,
the process being accelerated by the pulling up of the lower portion
324 DIGESTION
of the pharynx over the bolus by the action of the palato- and stylo-
pharyngei.
The second or cesophageal portion of the involuntary stage is
a more leisurely performance. The bolus is carried along by a
peculiar ' peristaltic ' contraction of the muscular wall of the
oesophagus, which travels down as a wave, constricting the tube
and pushing the food before it. In front of the constricting wave
moves a wave of inhibition, so that the part of the oesophagus into
which the bolus is about to pass is always relaxed, while the part
behind it is contracted. This exact co-ordination of inhibition
and contraction is the essential thing in peristalsis. When the food
reaches the lower end of the gullet the tonic contraction of that part
of the tube is for a moment relaxed by reflex inhibition, and the
morsel passes into the stomach. Beaumont saw, in the case of
St. Martin, that the oesophageal orifice of the stomach contracted
firmly after each morsel was swallowed, and so did the gastric walls
in the neighbourhood of the fistula when food was introduced by
this opening. In the dog the whole process of swallowing from
mouth to stomach has been shown to occupy four to five seconds,
but the time is by no means constant. In man the peristaltic wave
requires about five to six seconds to travel from the level of the
glottis to the cardiac orifice. The rate of movement is greater in the
upper than in the lower portion of the oesophagus.
Such is the mechanism of deglutition when the bolus is of such
consistence and size that it actually distends the oesophagus. But
it has been shown that liquid food is swallowed in a different way.
The food lying on the dorsum of the tongue, suddenly put under
pressure by the sharp contraction of the mylo-hyoid muscles, is
shot rapidly down to the lower part of the lax oesophagus, or, occa-
sionally, some of it even into the stomach. So far the process has
only occupied one-tenth of a second. After several seconds, the
food, or the portion which still remains in the oesophagus, is forced
through the cardiac sphincter into the stomach by the arrival of
the tardy peristaltic contraction of the cesophageal wall (Kronecker
and Meltzer). Two sounds may be heard in man on listening in
the region of the stomach or oesophagus during deglutition of liquids,
especially when, as generally happens, they are mixed with air.
The first sound occurs at once, and is due to the sudden squirt of
the liquid along the gullet ; the second, which is heard after a distinct
interval (about six seconds), is caused by the forcing of the fluid
through the cardiac orifice of the stomach by the contraction of the
oesophagus.
There are certain peculiarities which distinguish this peristaltic
movement of the oesophagus from that of other parts of the alimen-
tary canal. It is far more closely related to the central nervous
system, and, unlike the peristaltic contraction of the intestine, can
THE MECHANICAL PHENOMENA OF DIGESTION 3*5
pass over any muscular block caused by ligature, section, or crush-
ing, so long as the nervous connections are intact. But division
of the cesophageal nerves causes, as a rule, stoppage of oesophageal
movements; although an excised portion of the tube retains its
vitality for a long time, and may, under certain circumstances, go
on contracting in the characteristic way after removal from the body
(p. 8i>). Stimulation of the mucous membrane of the pharynx will
cause reflex movements of the oesophagus, while stimulation of its
own mucous membrane is ineffective. From these facts we learn
that although the cesophageal wall may possess a feeble power of
spontaneous peristaltic contraction, yet this is usually in abeyance,
or at least overmastered by central nervous control ; so that impulses
discharged as a ' fusillade ' from successive portions of the vagus
centre, and travelling down the oesophageal nerves, excite the
muscular fibres in regular order from the upper to the lower end
of the tube.
Nervous Mechanism of Deglutition. — 'The centre for the whole
involuntary stage (both pharyngeal and oesophageal) lies in the
upper part of the medulla oblongata. When the brain is sliced
away above the medulla, deglutition is not affected ; but if the upper
part of the medulla is removed, the power of swallowing is abolished.
In man, disease of the spinal bulb interferes far more with deglutition
than disease of the brain proper.
Normally, the afferent impulses to the centre are set up by the
contact of food or saliva with the mucous membrane of the posterior
part of the tongue, the soft palate and the fauces, the nerve-
channels being the superior laryngeal, the pharyngeal branches of
the vagus, and the palatal branches of the fifth nerve.* A feather
has sometimes been swallowed involuntarily by a reflex movement
of deglutition set up while the soft palate or pharynx was being
tickled to produce vomiting. Artificial stimulation of the central
end of the superior laryngeal will cause the movements of deglutition
independently of the presence of food or liquid; but if the central
end of the glosso- pharyngeal nerve be stimulated at the same time,
the movements do not occur. The glosso-pharyngeal is therefore
able to inhibit the deglutition centre, and it is owing to the action
of this nerve that in a series of efforts at swallowing, repeated within
less than a certain short interval (about a second), only the last is
successful. It is also through the glosso-pharyngeal nerve that
the respiratory movements are inhibited during deglutition. When
the central end of this nerve is stimulated, respiration is stopped
* It appears that the most influential reflex paths may differ in different
animals. In the rabbit, e.g., the reflex is set up by excitation of the trigeminal
fibres which supply the mucous membrane anterior to the tonsils, in the dog
and cat by excitation of the glosso-pharyngeal fibres in the posterior wall of
the pharynx, and in monkeys by excitation of the trigeminal branches dis-
tributed to the mucous membrane over the tonsils (Kahn).
326 DIGESTION
for four or five seconds, and this cessation is distinguished from
that produced by any other afferent nerve by the circumstance
that it occurs not in expiration exclusively or in inspiration ex-
clusively, but with the respiratory muscles in the precise degree of
contraction in which they happened to be at the moment of stimu-
lation. The efferent nerves of the reflex act of deglutition are the
hypoglossal to the tongue and the thyro-hyoid and other muscles
concerned in raising the larynx; the glosso-pharyngeal, vagus,
facial and fifth to the muscles of the palate, fauces, and pharynx;
the fifth to the mylo-hyoid; and the vagus to the larynx and
oesophagus. Section of the vagus interferes with the passage of
food along the oesophagus; stimulation of its peripheral end causes
cesophageal movements.
Movements of the Stomach. — The whole of the stomach does
not take part equally in the movements associated with digestion.
We may divide the organ, both anatomically and functionally, into
two portions — a pyloric portion, or antrum pylori, comprising about
a fifth of the stomach, and a larger cardiac portion, or fundus*
At the junction of the antrum and the fundus the circular muscular
coat is slightly thickened into a ring called the ' transverse band/
or ' sphincter of the antrum.' In the living stomach the region
of the transverse band is usually contracted so strongly and con-
tinuously that a distinct groove is seen to separate the tubular
antrum from the bag-like cardiac end. The suggestion of a massive
constricting ring of muscle is belied by an examination of the dead
viscus. The transverse band is really little more than a physio-
logical sphincter. The empty stomach is contracted and at rest.
A few minutes after food is taken contractions begin in the antrum,
and run on in constricting undulations (in the cat at the rate of
six in the minute) towards the pyloric sphincter. Each wave takes
about twenty seconds (in the cat) to pass from the middle of the
stomach to the pylorus. Feeble at first, they become stronger and
stronger as digestion proceeds, and gradually come to involve the
portion of the fundus next the sphincter of the antrum, but their
direction is always towards the pylorus, never, in normal diges-
tion, away from it. The food is thus subjected to energetic churn-
ing movements in the pyloric end of the stomach, and worked up
thoroughly with the gastric juice. Kept in constant circulation,
it gradually becomes reduced to a semi-liquid mass, the chyme,
which is at intervals driven against the pylorus by strong and
regular peristaltic contractions of the lower end of the stomach,
* Here ' fundus ' is used in the sense in which it is generally employed in
speaking of the stomach of the dog 01 cat as signifying the wnole of the organ
with the exception of the antrum pyiori. By the fundus of the human stomach
most writers mean only the cul-'Je-sac at the cardiac end; the portion inter-
vening between it and the aucrum pylori is often termei the body of the
ttomach.
THE MECHANICAL PHENOMENA OF DIGESTION
327
II A.M
the sphincter relaxing from time to time by a reflex inhibition to
admit the better-digested portions into the duodenum, but tighten-
ing more stubbornly at the impact of a hard and undigested morsel.
The nature, as well as the consistence of the food, influences the
length of its sojourn in the stomach. Carbo-hydrate food passes
more rapidly through the pylorus than fatty food, and fat more
rapidly than protein. The reason is that
the acidity of the gastric juice varies
with the different kinds of food, hydro-
chloric acid being secreted in abundance
in the presence of proteins, and to a
much smaller extent in the presence of
fats and carbo-hydrates. Now, dilute
hydrochloric acid when introduced into
the stomach remains there for a much
longer time than water. This depends
upon the fact that such portions of the
acid as get into the duodenum stimulate
afferent fibres in its mucous membrane,
and so cause reflex spasm of the pyloric
sphincter. When the acid chyme be-
comes neutralized to a certain point by
the bile and pancreatic juice, inhibitory
impulses pass up from the duodenum
and cause the sphincter to relax. The
cardiac division of the stomach, with
the exception of the portion that borders
the transverse band, takes no share in
the peristaltic movements. And, indeed,
it is far more difficult to cause such con-
tractions by artificial stimulation in the
fundus* than in the pylorus. The two
portions of the stomach are partially, or
in certain animals from time to time
completely, cut off from each other by
the contraction of the sphincter of the
antrum. The fundus, so far as its
mechanical functions are concerned, acts
chiefly as a reservoir for the food, which,
like a hopper, it gradually passes into
the pyloric mill as digestion goes on by a tonic contraction of its
walls. The existence of this reservoir enables larger quantities of
food to be taken at one meal, which can then be digested gradually.
* The common idea, however, that the fundus is completely inactive is
erroneous. Rhythmical variations in tone with a period of i to 3 minutes have
been observed during digestion. In hunger vigorous peristaltic contractions
sweep over the whole stomach, beginning at the cardiac end.
Fig. 150. — Cat's Stomach seen
by Rontgen Rays (Cannon).
The outlines of the stomach
containing food mixed with
bismuth subnitrate were
drawn at intervals from
ii a.m. to 4.30 p.m.
DIGESTION
These facts have been mainly ascertained by v observations on
animals, such as the dog and the cat, either by direct inspection
after opening the abdomen (Rossbach), or in the intact body, under
absolutely physiological conditions, by means of the Rontgen rays
(Cannon). In the latter method the food is mixed with subnitrate
of bismuth, which is opaque to these rays, so that when the animal
is looked at through a fluorescent screen the stomach appears as a
dark shadow in the field (Fig. 150). This method has even been
applied with success to the study of the passage of the food along
the human alimentary canal from deglutition to defaecation (Hertz).
It has been shown in this way that in the living body in the erect
position the long axis of the stomach is much more nearly vertical
than had been supposed. When food is taken it sinks into the
lower (pyloric) end, and at the upper end gas collects.
When the person lies down the lower end of the stomach passes
more towards the left, so that the long axis lies more transversely.
Other methods have thrown light on the gastric movements — e.g.,
direct inspection through a fistula of the stomach, and the study
Fig. 151. — Human Stomach studied by Roatgen Rays, a. Empty stomach in ver-
tical position ; b, shortly after a meal (peristaltic contractions are occurring at
the pyloric end) ; c, full stomach in vertical position. (Halliburton after Hertz.)
of records showing the changes of pressure in the viscus obtained
by means of small balloons introduced into it. Such balloons
attached to a rubber tube have been swallowed by normal men
and kept for long periods in the stomach (Carlson). Even in the
excised stomach, kept in salt solution at the body-temperature,
the typical movements can be observed proceeding for some time.
Movements of the Small Intestine. — In the small intestine two
kinds of movements are to be seen : (i) Gentle, swaying, ' pendulum '
movements, sometimes irregular, but often recurring rhythmically
at the rate (in the dog) of 10 or 12 in the minute. Both the longi-
tudinal and the circular muscular coats contract, causing slight
waves of constriction, which may originate at any part of the gut,
but, under normal circumstances, nearly always travel from above
downwards, with a velocity of 2 to 5 centimetres per second. These
movements cause the coils of the intestine to sway gently from side
THE MECHANICAL PHENOMENA OF DIGESTION 329
to side. Under abnormal conditions, as in the exposed ' surviving '
intestines of the rabbit, contractions, probably similar to the
pendulum movements, but running indifferently in both direc-
tions, can be set up by local stimulation. The function of these
pendulum movements seems to be the thorough mixing of the food
with the digestive juices in the intestine. When an animal is fed
with food containing bismuth subnitrate and observed with the
Rontgen rays, it is seen that the food in a coil is often divided into
small segments, which then join together to form longer masses,
these being in turn again divided. This segmentation is rhyth-
mically repeated (in the cat at the rate of thirty times a minute).
Although of itself it insures only the mixing of the contents of the
gut, and not their onward progress, it is usually accompanied by
peristalsis, so that while the food is undergoing segmentation it is
also slowly passing down the intestine. Often, however, a column
of food remains for a considerable time, dividing, uniting, and divid-
ing again, without sensibly shifting its position. In addition to the
relatively rapid pendulum movements, much slower periodic varia-
tions of tone of the whole musculature may be normally observed.
(2) True peristaltic movements, in which a ring of constriction,
obliterating the lumen, moves slowly down the tube, with a speed,
it may be, no greater than i mm. per second. The portion of the
intestine immediately below the advancing constriction is relaxed
and motionless, so that we may say that a wave of inhibition pre-
cedes the wave of contraction. The peristaltic movements of the
small intestine, the most typical of their kind, are most easily
excited by mechanical stimulation of the mucous membrane, as
by the contact of a morsel of food or an artificial bolus of cotton-
wool. Travelling, under normal conditions, always downwards,
the constriction squeezes the contents of the tube before it, and the
wave usually ends at the ileo-csecal valve, which separates the small
intestine from the large. The cause of the definite direction of the
peristaltic wave is grounded in the anatomical relations of the
intestinal wall. For when a portion of the intestine is resected,
turned round in its place and sutured, so that what was before its
upper is now its lower end, the contraction wave is unable to pass,
and the obstruction to the onward flow of the intestinal contents
causes marked dilatation of the gut, and sometimes serious disturb-
ance of nutrition. The most probable explanation is that the peri-
stalsis is governed by a local reflex nervous mechanism (Auerbach's
plexus), the stimulation of which by the contact of the food with
the mucous membrane or by the distension of the gut "causes
excitation of the circular muscular fibres above the point of stimula-
tion, and inhibition of them below it. The automatic pendulum
movements, and also the slow, rhythmical variations of tone, have
a different relation to the local nervous mechanism, for they behave
differently to poisons like cocaine and nicotine, which act on that
33<> DIGESTION
mechanism. The pendulum movements are, if anything, increased
in intensity and made more regular. But the peristaltic waves,
although they can be locally excited by direct stimulation of the
muscular fibres, are no longer propagated, and a bolus introduced
into the intestine remains at rest where it is placed. Some have
interpreted these facts as indicating that the pendulum movements
are myogenic in origin. But evidence has lately been obtained that,
although they are not reflex movements elicited by afferent impulses
from the mucous membrane, since they continue in unaltered in-
tensity, in isolated loops of intestine immersed in Ringer's (or
Locke's) solution (p. 66) after removal of both mucosa and sub-
mucosa, they are nevertheless dependent upon Auerbach's plexus.
For when the circular muscular coat is separated from this plexus,
the automatic movements of this coat are abolished, although the
excitability of the musculature to
direct stimulation is not affected.
The longitudinal coat, which is
still in connection with Auerbach's
plexus, goes on contracting spon-
taneously (Magnus). Under certain
conditions a movement of food or
secretions in the reverse of the
normal direction can be set up in
the small intestine in the intact
body — e.g., in the case of obstruc-
Fig. 152.— Intestine Segment beating tion of the intestine leading to
in Ringer's Solution. At 6 the oxy- vomiting of its Contents. But this
gen stream was increased. To be does not necessarily indicate a re-
read from left to right. Time trace, , , ,, J , .. ,. .
half-minutes. (Reduced to one -half.) versal of the normal direction of
the peristalsis. Such a reversal,
if it occurs at all, is not easy to realize by artificial stimulation, and
even when an antiperistaltic wave is apparently started, it travels
up the intestine only for a short distance and then dies out. A
third variety of intestinal movement has sometimes been described,
the so-called ' peristaltic rush ' (Meltzer, etc.). It consists of a
rapidly moving peristaltic contraction, preceded by relaxation of
a long portion of the tube. Such a contraction may even sweep
down without pause from the duodenum to the end of the ileum.
The Movements of the Large Intestine differ from those of the
small mainly in the great frequency of antiperistalsis. This, indeed,
seems to be the usual movement of the transverse and ascending
colon. The antiperistalsis recurs in periods about every fifteen
minutes, and each period generally lasts about five minutes. The
constrictions, running towards the caecum, thoroughly churn and
mix the remnants of the food, a considerable absorption of which
may take place in the upper part of the large intestine. Regurgita-
tion into the ileum in man is prevented partly by the oblique entry
THE MECHANICAL PHENOMENA OF DIGESTION 331
of the ileum through the wall of the colon (so-called ileo-caecal
valve), but essentially by the tonic contraction of the ileo-colic
sphincter. The sphincter usually permits the passage of material
only in the direction from small to large intestine. But as an
occasional phenomenon, a reverse movement may occur. Thus
food may actually pass back through the ileo-colic sphincter into
the small intestine under the action of a long-continued and vigorous
antiperistalsis, and in this way a considerable portion of a bulky
enema may be eventually disposed of (Cannon). This so-called
antiperistalsis is not precisely the same kind of movement, leaving
out of account its direction, as the peristalsis already described in the
small intestine, since it is not preceded by a wave of inhibition.
True peristaltic contractions preceded by relaxation of the gut may
also be observed to start in the caecum, and to travel down the large
intestine. They are not very frequent in comparison with those
of the small intestine, and they die away before reaching the end
of the colon, allowing the food to be driven back again towards
the caecum by the antiperistalsis. A true downward peristalsis
is more commonly seen in the descending colon, and is here asso-
ciated with the propulsion and collection of the faeces, which are
mainly stored in the sigmoid flexure. These peristaltic contractions
do not normally reach the rectum, which, except during defaecation,
remains at rest.
Influence of the Central Nervous System on the Gastro- Intestinal
Movements. — As we have already said, these movements are much
less closely dependent on the central nervous system than are those
of the oesophagus. They can not only go on, but are in general
better marked when the extrinsic nervous connections are cut; they
cannot spread when the continuity of the tube is destroyed, and
the mere presence of food will excite them when other than local
reflex action has been excluded by section of the nerves. Never-
theless, the central nervous system does exercise some influence
in the way of regulation and control, if not in the way of direct
initiation of the movements, and the swallowing or even the smell
of food has been observed to strengthen the contractions of a loop
of intestine severed from the rest, but with its nerves still intact.
The vagus is the efferent channel of this reflex action : stimulation
of its peripheral end may cause movements of all parts of the
alimentary canal from cesophagus to large intestine, and may
strengthen movements already going on; but section of it does not
stop them, nor hinder the food from causing peristalsis wherever
it comes. The vagus also contains inhibitory fibres for the lower
end of the cesophagus and the whole of the stomach. Stimulation
of it is followed first by inhibition, and then, after an interval, by
an increase of tone and augmentation of the contraction of the
whole stomach, including the cardiac and pyloric sphincters. The
332 DIGESTION
splanchnic nerves contain fibres by which the intestinal movements
can be inhibited, and they appear to be always in action, for after
section of these nerves the movements are strengthened. On the
other hand, stimulation of the peripheral end of the cut splanchnic
causes arrest of the movements. Occasionally, however, it has
the opposite effect. Contractions of the small intestine are more
easily caused by excitation of the vagus after the inhibitory splanch-
nic nerves have been cut. The splanchnics also contain inhibitory
fibres for the stomach, and it is only when these are intact that
complete reflex inhibition of the organ can be obtained in the rabbit
(Auer). The gastric movements are not permanently affected by
section of these nerves alone, or even by simultaneous section of
the splanchnics and the gastric branches of the vagi. But if the
vagi are cut while the splanchnics remain intact, the peristalsis of
the stomach is weakened, its onset delayed, and the proper emptying
of the viscus through the pylorus interfered with. In all probability
these results are due to the uncontrolled action of the inhibitory
fibres. The splanchnics have a special relation to the ileo-colic
sphincter, which closes when they are stimulated, and becomes in-
sufficient when they are cut. The vagus does not affect it.
The lower part of the large intestine is influenced by the sacral nerves
(second, third, and fourth sacral in tlie rabbit), and by certain lumbar
nerves, in the same way as the higher parts of the alimentary canal, and
particularly the small intestine, are influenced by the vagus and the
splanchnics. Stimulation of these sacral nerves within the spinal
canal, or of the pelvic nerves (nervi erigentes) into which they pass,
causes contraction of the parts of the large intestine concerned in
defaecation — that is, in the dog, of the whole colon, with the exception
of the caecum; in the cat, of the distal two-thirds of the colon. The
colon first undergoes rapid shortening due to the contraction of the
longitudinal fibres and the recto-coccygeus muscle. After a few
seconds this is followed by contraction of the circular fibres, beginning
at the lower limit of the region in which antiperistalsis can occur, and
spreading downwards, so as to empty the portion of the bowel involved
in the contraction. This is a very close imitation of what occurs in
natural defaecation. In man the parts involved in these movements
are probably the sigmoid flexure and rectum. In addition to these
characteristic motor effects on the lower part of the large intestine,
stimulation of the pelvic nerves causes an increase in the antiperistalsis
of its upper portions. Stimulation of the lumbar nerves or of the por-
tions of the sympathetic into which their visceral fibres pass (lumbar
sympathetic chain from second to sixth ganglia, or the rami from it to
the inferior mesenteric ganglia) causes inhibition of the movements of
the caecum and the whole colon, including the antiperistaltic move-
ments. Excitation of the sacral nerves initiates or increases the con-
traction of both coats of the portions of the large intestine on which
they act, excitation of the lumbar nerves inhibits both. And in the small
intestine the same law holds good ; the two coats are contracted together
by the action of the vagus or inhibited together by that of the splanchnics.
Defaecation is partly a voluntary and partly a reflex act. But
in the infant the voluntary control has not yet been developed;
THE MECHANICAL PHENOMENA OF DIGESTION 333
in the adult it may be lost by disease; in an animal it may be
abolished by operation, and in each case the action becomes wholly
reflex. Owing to the tonic contraction of the rectum and the acute
angle formed at the pelvi-rectal flexure, the faeces are arrested at
this point. In consequence the pelvic colon becomes filled with
faeces from below upwards, and the rectum remains empty till
immediately before defalcation. This has been verified in man by
observations with the Rontgen rays (Hertz). In persons whose
bowels are opened regularly after breakfast, the passage of faeces
into the rectum gives rise to the characteristic sensation which
may be termed the ' call to defaecation. ' It is the distension of the
rectum, and of the rectum alone, which is associated with this
sensation, for in persons from whom the entire rectum has been
removed for malignant disease the sensation is absent, and it may
be elicited by artificially distending the rectum, though not any
other part of the alimentary canal. The minimum pressure required
to elicit the sensation is smaller the greater the length of the gut
exposed to it, varying in one individual from 32 to 48 mm. of
mercury, according to the length of a balloon introduced into the
rectum. The passage of the faeces from the pelvic colon into the
rectum is due to the discharge of that reflex contraction of the lower
portion of the bowel already described (p. 332), of which the pelvic
nerves constitute the efferent path. This reflex peristalsis is elicited
by various causes, among which one of the most important is the
taking of food at breakfast into the empty stomach, and another
the muscular activity associated with getting up and dressing.
The desire to defalcate may for a time be resisted by the will, or it
may be yielded to. In the latter case the abdominal muscles, and,
according to Hertz, the diaphragm also, are forcibly contracted;
and the glottis being closed, the whole effect of their contraction
is expended in raising the pressure within the abdomen and pelvis,
and so aiding the muscular wall of the bowel itself in driving the
faeces from the sigmoid flexure to the rectum. The two sphincters
which close the anus — the internal sphincter of smooth muscle,
and the external of striated — are now relaxed by the inhibition of
a centre in the lumbar portion of the spinal cord, through the
activity of which the tonic contraction of the sphincters is normally
maintained. This relaxation is partly voluntary, the impulses
that come from the brain acting probably through the medium
of the lumbar centre. But in the dog, after section of the cord in
the dorsal region, the whole act of defaecation, including contraction
of the abdominal muscles and relaxation of the sphincters, still
takes place, and here the process must be purely reflex. Even after
complete destruction of the lumbar and sacral portions of the spinal
cord the tone of the sphincters returns after a time, and defalcation
is carried on as in a normal animal, the control of the sphincters
334 DIGESTION
being due either to a property of the muscular tissue itself or to
local ganglia. The contraction of the levatores ani helps to resist
overdistension of the pelvic floor and to pull the anus up over the
faeces as they escape. The nervi erigentes carry efferent constrictor
fibres, and the hypogastrics, as a rule, efferent dilator fibres, to the
sphincters. While the internal sphincter is by itself capable of
maintaining a tonus of considerable strength, the external sphincter
contributes an important share (30 to 60 per cent.) to the closure
of the rectum. If the call to defaecation is neglected, the desire
passes away. This is not due to the faeces being carried back into
the pelvic colon by antiperistalsis, as has generally been stated.
The faeces which have passed into the rectum remain there, as can
be shown by examination with the finger after the desire to empty
the bowels has disappeared. The reason for the disappearance
of the sensation is the relaxation of tone which occurs in the
muscular coat of the rectum after a period of distension. It is not
till it has been again distended by the entrance of a further portion
of faeces that the call to defaecation is again experienced. When
the call is repeatedly neglected, the sensibility of the rectum to dis-
tension becomes blunted, and this is a common cause of constipation.
The time of passage of substances through the alimentary canal
has been studied by administering collodion capsules filled with
subnitrate of bismuth to human beings, and observing their pro-
gress by taking shadow pictures of them at intervals with the
Rontgen rays. During the first twenty minutes two such capsules
swallowed at the same time by a healthy young man were clearly
seen in the greater curvature of the stomach, but in the interval
between the first half-hour and the seventh or eighth hour no further
trace of them was detected. About the eighth hour they re-
appeared in the caecum, where they remained with little or no
onward movement till the fourteenth hour. From the fourteenth
to the sixteenth hour they travelled along the ascending colon, and
tarried a long time at the left angle of the colon. From the nine-
teenth to the twenty-second or twenty-fourth hour they slowly
passed downward in the descending colon, and stopped at the sig-
moid flexure till their expulsion in defaecation. In some subjects
the entire passage of the capsules was complete in sixteen hours, in
others not until after thirty hours. A one cent piece swallowed by
a healthy child four years old was recovered in the fasces 52 hours
later, and a button, slightly larger, swallowed by the same child,
appeared after almost exactly the same interval.
Vomiting. — We have seen that under normal conditions the
movements of the alimentary canal always tend to carry the food
in one definite direction, along the tube from the mouth to the
rectum. The peristaltic waves generally run only in this direction,
and, further, regurgitation is prevented at three points by the
THE MECHANICAL PHENOMENA OF DIGESTION 335
cardiac and pyloric sphincters of the stomach and the ileo-colic
sphincter and valve. But in certain circumstances the peristalsis
may be reversed, one or more of the guarded orifices forced, and the
onward stream of the intestinal contents turned back. In obstruc-
tion of the bowel, the faecal contents of the large intestine may pass
up beyond the ileo-caecal valve, and, reaching the stomach, be driven
by an act of vomiting through the cardiac orifice; in what is called
a ' bilious attack,' the contents of the duodenum may pass back
through the pylorus and be ejected in a similar way; or, what is
by far the most common case, the contents of the stomach alone
may be expelled.
Vomiting is usually preceded by a feeling of nausea and a rapid
secretion of saliva, which perhaps serves, by means of the air
carried down with it when swallowed, to dilate the cardiac orifice
of the stomach, but may be a mere by-play of the reflex stimula-
tion bringing about the act, since evidence of stimulation of other
bulbar centres (vaso-motor and cardio-inhibitory) has also been
obtained. The diaphragm is now forced down upon the ab-
dominal viscera, first with open and then with closed glottis. The
thoracic portion of the oesophagus is thus placed under diminished
pressure, and therefore widened, while saliva and air are aspirated
into it out of the mouth. The abdominal muscles strongly con-
tract. At the same time the stomach itself, and particularly
the antrum pylori, contracts, the cardiac orifice relaxes, and the
gastric contents are shot up into the lax oesophagus, and through
it into the pharynx, and issue by the mouth or nose. The move-
ments of the stomach during vomiting induced by apomorphine
have been studied in the cat by the Rontgen ray method. There is
first observed extreme relaxation of the cardiac end; then a deep
constriction appears a little below the cardiac orifice, and runs
towards the pylorus, increasing in depth as it goes. When the
transverse band is reached, this contracts firmly and remains con-
tracted, and the constriction passes on over the antrum pylori.
Ten or twelve similar waves follow, at the end of which time the
constriction in the region of the transverse band divides the stomach
into the firmly-contracted antrum and the relaxed fundus. Now
follows a sudden contraction of the diaphragm and abdominal
muscles accompanied by the opening of the cardiac orifice. Either
the diaphragm and abdominal muscles alone, without the stomach,
or the diaphragm and stomach together, without the abdominal
muscles, can carry out the act of vomiting. For an animal whose
stomach has been replaced by a bladder filled with water -can be
made to vomit by the administration of an emetic (Magendie) ;
and Hilton saw that a man who lived fourteen years after an injury
to the spinal cord at the height of the sixth cervical nerve, which
caused complete paralysis below that level, could vomit, though
with great difficulty. In a young child in which very slight causes
336 DIGESTION
will induce vomiting, the stomach alone contracts during the act.
But in the adult such a contraction is ineffectual, and the same la
the case in animals, for a dog under the influence of a moderate
dose of curara, which paralyzes the voluntary muscles but not the
stomach, cannot vomit.
The nerve-centre is in the medulla oblongata. It may be
excited by many afferent channels : the sensory nerves of the fauces
or pharynx, of the stomach or intestines (as in strangulated hernia) ,
of the liver or kidney (as in cases of gall-stone or renal calculi), of
the uterus or ovary, and of the brain (as in cerebral tumour), are
all capable, when irritated, of causing vomiting by impulses passing
along them to the vomiting centre.
The vagus nerve in man certainly contains afferent fibres by the
stimulation of which this centre can be excited, for it has been
noticed that when the vagus was exposed in the neck in the course
of an operation, the patient vomited whenever the nerve was
touched (Boinet, quoted by Gowers). In meningitis, vomiting is
often a prominent symptom, and is sometimes due to irritation of
the vagus nerve by the inflammatory process.
Some drugs act as emetics by irritating surfaces in which efficient
afferent impulses may be set up, the gastric mucous membrane,
for example; sulphate of zinc and sulphate of copper act mainly
in this way. Apomorphine, on the other hand, stimulates the
centre directly, and this is also the mode in which vomiting is pro-
duced in certain diseases of the medulla oblongata. The efferent
nerves for the diaphragm are the phrenics, for the abdominal
muscles the intercostals. The impulses which cause contraction
of the stomach pass along the vagi. Dilatation of the cardiac
orifice is brought about by the inhibitory fibres in the vagus already
mentioned.
SECTION III. — THE CHEMISTRY OF THE T IGESTIVE JUICES.
Ferments. — The chemical changes wrought in the food as it
passes along the alimentary canal are due to the secretions of
various glands which line its cavities or pour their juices into it
through special ducts. These secretions owe their power for the
most part to substances present in them in very small amount,
but which, nevertheless, act with extraordinary energy upon the
various constituents of the food, causing profound changes with-
out, upon the whole, being themselves used up, or their digestive
power affected. The active agents are the enzymes, sometimes
spoken of as unformed or unorganized ferments — unorganized
because their action does not depend upon the growth of living
cells, which was long supposed to be the case for some other fer-
ments, such as yeast. Since it has been shown that specific enzymes
can be separated from cells which were formerly believed to act
33?
by their mere growth, the distinction between formed and unformed
ferments has lost its significance, and has to a great extent been
superseded by the distinction between intra- and extra-cellular
enzymes (also called endo- and exo-enzymes) — i.e., between
ferments which normally act in the interior of the cells where they
are produced and ferments which act outside of the cells that secrete
them. From yeast cultures, for instance, by crushing the cells,
a ferment (zymase*) can be obtained which in the complete absence
of living yeast-cells, and, indeed, of any living micro-organism, forms
alcohol and carbon dioxide from sugar, just as living yeast does.
There is every reason to believe that it is by the intracellular action
of this endoenzyme that the yeast-cell normally causes alcoholic
fermentation. The digestive ferments are typical extracellular
enzymes. Their chemical nature has not been exactly made out;
some of them at least do not appear to be proteins, or to contain
a protein group. Many of them apparently exist in the colloidal
condition, although this has not been shown for all. In certain
cases the more or less stable union of a definite inorganic substance
with the ferment, or its actual inclusion in the ferment molecule,
seems to be a condition of its action. Thus there is reason to believe
that in gastric digestion hydrochloric acid is loosely combined with
the pepsin. In the plant oxydase, laccase (p. 272), manganese is
present. And the fact that manganese salts oxidize certain substances
as laccase does suggests that it is the manganese in combination
with some protein or other organic compound in the ferment
molecule which confers upon laccase its oxidizing power. A similar
relation between iron and some animal oxydases is possible, though
not definitely proved. But none of the ferments of the digestive
juices has as yet been satisfactorily isolated, and at present it is
only by their effects that we recognize them. The difficulty of
isolating them is increased by the fact that, like other colloids,
they readily adhere to surfaces, and are carried down by the most
diverse precipitates of substances to which they are chemically
indifferent. On the other hand, this very property is taken advan-
tage of to procure more concentrated, although still impure, solutions
of them than exist in the natural secretions. Thus in the prepara-
tion of many ferments the first step is to produce an inert pre-
cipitate, such as calcium phosphate, in the juice or extract. Some
of the ferments act best in an alkaline, some in an acid medium.
They all agree in having an ' optimum ' temperature, which is more
favourable to their action than any other ; a low temperature sus-
pends their activity, and boiling abolishes it for ever. The
optimum temperatures of the majority of enzymes lie between
* Ferments are usually designated by names with the termination ' ase,'
and indicating the kind of substances on which they act, or sometimes their
source. Thus proteases are ferments acting on proteins, amylases ferments
acting on starch, etc.
3?* DIGESTION
37° and 53° C. ; the ' killing ' temperatures between 60° and 75* C.
when they are heated in solutions, but considerably higher when
they are heated dry. The action of the digestive enzymes is
hydrolytic — i.e., it is accompanied with the taking up of the elements
of water by the substance acted upon. The accumulation of the
products of the action first checks and then arrests it. In many
cases this seems to be due to combination of the ferment with one
or other of the end products, and the consequent segregation of
the ferment from the reaction mixture. The enzyme is not affected
indiscriminately by any of the end products. On the contrary,
their action is curiously selective. Thus the hydrolysis of lactose
by lactase is retarded by galactose, but not by the other end
product dextrose. The hydrolysis of cane-sugar by invertase is
retarded by levulose, but not by dextrose. The splitting of the
dipeptid (p. 2) glycyl-/-tyrosin by a ferment in the expressed juice
of yeast-cells is greatly delayed by one of the products (/-tyrosin),
but not by the other (glycocoll). Combination of the ferment with
an end product is not, however, the only way in which the reaction
may stop before the whole of the substrate, as the substance
acted on by the ferment is termed, has been changed. It has been
demonstrated in some cases that this is due to the action of the
enzymes being reversible. For example, lipase (p. 363) not only
decomposes the esters ethyl butyrate or glycerin butyrate, but
also builds them up again from the decomposition products — ethyl
butyrate from ethyl alcohol and butyric acid, glycerin butyrate from
glycerin and butyric acid (Kastle and Loevenhart, Hanriot). Thus:
C3H7COOC2H5 +H2O^=?'C3H7COOH + C2H6OH.
Kthyl butyrate. Water. Butyric acid. Ethyl alcohol.
The action of the enzyme is merely to accelerate the establish-
ment of the proportions in which the four bodies entering into the
reaction are in equilibrium, and the point of equilibrium is the same
whether we start from one or the other side of the equation repre-
senting the reaction. Such reversible reactions in the presence of
enzymes seem to afford the key to the explanation of many of the
syntheses which are known to occur in the body. Sometimes the
action is not strictly reversible in the sense that precisely the original
material is reconstructed, but from the products of the hydrolysis
substances are synthesized or condensed, which are then incapable
of being split by the ferment. When a concentrated solution of
dextrose is acted on for a long time by yeast maltase, a ferment
obtained from yeast which changes maltose into dextrose, some of
the dextrose is reconverted into isomaltose and dextrin-like bodies.
Isomaltose is not again hydrolysed by maltase. The ferment
emulsin contained in almonds behaves in the converse way. It
hydrolyses isomaltose so as to form dextrose, and then condenses
dextrose to maltose (Armstrong).
THE CHEMISTRY OF THE DIGESTIVE /VICES 339
Many of the ordinary substances of the laboratory will accelerate
reaction which goes on slowly in their absence. These are called
catalysers. Some writers also speak of catalysers which retard
a reaction progressing quickly in their absence. The process by
which the reaction is accelerated (or retarded) is termed catalysis.
A typical catalyser can exert its action when it is present in ex-
ceedingly small amount in comparison with the substance acted
upon. However it may enter into the reaction, it does not take
part in the formation of the final products nor contribute to the
energy changes, and for this reason is often apparently unaltered
at the end of the process. The catalysers have therefore been
compared to the lubricants used for machinery as contrasted with
the coal or other source of energy. If it be remembered that the
expression is a purely metaphorical one, we may say that the
catalyst oils the reaction so that it slips on smoothly and swiftly
to an end-point which would, however, have been reached just the
same in time. A classical instance of catalysis is the inversion
of cane-sugar by weak acids, i.e., the change of the cane-sugar into
a mixture of equal quantities of dextrose and levulose — a reaction
which may be represented by the equation
= C6H12O6 + C6H12O6.
Cane-sugar. Water. Dextrose. Levulose.
This is a reaction which occurs also when the sugar is simply dis-
solved in water, but with extreme slowness at the ordinary tempera-
ture, although more rapidly at 100° C. The effect of the acid is
to catalyse the reaction, to markedly accelerate it. The hydrogen
ions of the free acid are responsible for the catalysis, and they are
not used up in the process, for the reaction at the end is unaltered.
The same action upon cane-sugar is exerted by an enzyme, invertase,
found in intestinal juice, although the laws governing the reaction
are somewhat different. Reversibility of the reaction can be even
more clearly demonstrated for catalysers than for enzymes. For
example, the condensation of acetone to diacetone-alcohol, which
is accelerated by hydroxyl ions (as by the addition of sodium
hydroxide, ammonia, etc.), only proceeds to a certain point, at which
equilibrium is established between the proportions of acetone and
the condensation product. Henceforth as much of the latter is
decomposed as is condensed. Thus :
2CH3.CO.CH3^=H>CH8.cb.CH2.C(CH3)2OH.
Acetone. Acetone alcohol.
On the other hand, the final equilibrium point need not be the same
for a catalyser and an enzyme. For example, amyl butyrate is
formed and decomposed according to the equation
C6HUOH +C3H7COOH«=II?' CgHyCOO.CgHn +H2O.
Amyl alcohol. Butyric acid. Amyl butyrate. Water.
$4« DIGESTION
The reaction can be accelerated either by a catalyst — e.g., H ions—
as by addition of free hydrochloric or picric acid, or by pancreas
lipase. When the concentrations of the reacting substances are
appropriately chosen, the same equilibrium point will be reached
from either side of the equation — i.e., the same percentage of the
butyric acid will be converted into the ester if we start with the
alcohol and acid, as will remain combined as ester if we start with
the amyl butyrate. But the proportion will not be the same when
the reaction is acclerated by H + as when it is accelerated by the
enzyme. And although it is probable that there is no fundamental
difference between the action of the digestive enzymes and that of
the inorganic catalysers, it is much too early to dogmatize.
Not even the m .rkedly specific action of the digestive ferments
can be considered an essential distinction. It is true that invertase
will act upon dextrose, and not at all upon maltose or lactase.
But there are other sugars, e.g., raffinose, a trisaccharide with the
formula QgHggOjg, obtained from beet-sugar residues, which it will
hydrolyse. Raffinose is made up of one molecule each of dextrose,
levulose, and galactose. On heating with dilute acids, it is decom-
posed into these substances. Invertase, however, only splits off
the levulose molecule, leaving a disaccharide isomeric, but not
identical with lactose. Similarly lactase, which is without action
upon cane-sugar or maltose, will hydrolyse the /3-galactosides, and
maltase, inert as regards cane-sugar or lactose, will hydrolyse the
a-glucosides. On the other hand, emulsin decomposes the /3-gluco-
sides, to which group most of the natural glucosides belong, as well
as the /3-galactosides and lactose. From raffinose emulsin splits
off galactose, leaving cane-sugar. Since the a and ft compounds
are isomeric, and differ not in their composition but in their struc-
ture, it has been concluded that the structure of the molecule of
a substance must be related to the structure of the enzyme which
can act on it, in some such way as a lock is related to its proper key.
Thus the key lactase fits in the lock lactose, but not in the lock
dextrose or the lock maltose. Although the same specificity is
not to be observed in the action of catalysers as in the action of
enzymes, it is not difficult to find many instances in which inorganic
substances show a marked limitation of their catalytic effects to
particular reactions. Thus hydriodic acid is slowly oxidized in
presence of hydrogen peroxide, with formation of iodine and water.
This reaction is accelerated by the addition of many substances,
e.g., tungstic acid. But tungstic acid has no catalytic effect on the
oxidation of hydriodic acid by bromic acid.
The existence of an optimum temperature for ferment action,
above which it rapidly decreases, and eventually comes to a com-
plete stop, is also in all probability only a superficial distinction
between enzymes and catalysers. For enzymes are easily altered,
THE CHEMISTRY OF THE DIGESTIVE JUICES 341
or even destroyed, at temperatures which very likely would favour
their action were they as thermostable as the majority of catalysing
agents. And inorganic catalysts are known which also show the
phenomenon of an optimum temperature depending on changes
produced in their physical condition when the temperature is
raised above this point. Thus a colloidal solution (or ' sol/ as it is
called) of platinum, prepared by passing electric sparks between
two platinum electrodes immersed in distilled water, and containing
the metal in the form of ultra-microscopic particles, acts as a cata-
lyser of a number of reactions. As the temperature is increased
up to a certain ' optimum,' the velocity of the catalysed reaction
is increased. But beyond this, as the boiling-point is approached,
the colloidal platinum is precipitated, and ceases to influence the
reaction.
As to the manner in which an enzyme increases the velocity of its
appropriate reaction, it is not easy to make any very positive statement.
Several possibilities are recognized, of which two have been especially
discussed, (i) The existence of the enzyme in colloidal solution may
be important. It is characteristic of colloidal solutions, in which the
dissolved substance is present in the form of extremely fine particles,
that the total surface of the particles is very great in proportion to
the mass of the substance in solution. Thus, a sphere of about the
same volume as the eyeball, with a diameter of, say, 2 centimetres,
would have a surface of 12*5 square centimetres. If this material were
subdivided into spheres of about tbe same volume as a leucocyte, with
a diameter of, say, 10 p, it would form eight thousand million of these
spheres, with a total surface of over i\ square metres. If the small
spheres were further subdivided into spherical particles, with a diameter
only the thousandth part of that of a leucocyte, say -^-, each would
form a thousand million of these particles, and the total surface of all
the particles would be about 2,500 square metres.
Now, it is known that the intensity of action of some of the inorganic
catalysers is proportional to the surface exposed. For example,
hydrogen peroxide, if left to itself, is slowly decomposed into water and
oxygen. The addition of finely divided v platinum, in the form of
platinum black, greatly hastens the decomposition, and the oxygen
bubbles off. The colloidal platinum sol is still more effective. The
nature of the surface effect is not entirely clear. One factor has been
thought to be an increase in the concentration of dissolved substances
or condensation of gases at the surface, and the better opportunity
for mutual action thus afforded to the ferment and the substrate.
The great extension of the surface cannot be the only factor in the
catalysis; otherwise any fine powder or suspension would have a cata-
lytic action. But kaolin, or fine sand, or colloidal solutions of ordinary
proteins or gelatin, have little, if any, effect on the decomposition of
hydrogen peroxide.
(2) Enzymes may produce their effects by contributing to the for-
mation of bodies intermediate between the substrate and the end-
products. If the time required for the formation of a given quantity
of the intermediate compound and the time required for the decom-
position of this compound into the final products of the ferment action
are in sum less than the time required for the direct change of the
DIGESTION
substrate into the end-products, the enzyme will clearly act as a cata-
lyser of the reaction. It has been shown that in the case of certain
inorganic catalysers this does occur. Thus, in the oxidation of hydriodic
acid by hydrogen peroxide, which has been already referred to,
molybdic acid has the power of acting as a catalyser. It has been proved
that the reaction occurs in two stages, permolybdic acid being first
formed by the action of the peroxide on molybdic acid. The permol-
ybdic acid then acts on hydriodic acid, producing iodine and water,
and being itself reduced again to molybdic acid, which therefore comes
out at the end of the reaction unchanged. The velocity of the double
reaction is much greater than that of the direct oxidation of hydriodic
acid by hydrogen peroxide.
There is evidence that the ferment actually combines with the sub-
strate, the combination then breaking up to form the end-products.
For instance, it has been shown that the amount of lactose hydrolysed
by lactase in a given time, when the ferment is present in very small
quantity in comparison with the substrate, is proportional to the con-
centration of the ferment, and independent of the concentration of
the lactose. Also with a given small concentration of ferment the
amount of lactose hydrolysed is at first the same for successive equal
intervals of time. These facts can only be explained by the assump-
tion that the ferment first combines with a portion of the substrate, the
rest of which remains inactive as regards the reaction, and that this
combination then takes up water and decomposes into the end-
products, in this case dextrose and galactose, setting free the ferment
to combine with another portion of the substrate.
The Quantitative Estimation of Ferment Action. — Since we have as yet
no certain method of freeing the digestive ferments from impurities,
our only quantitative test is their digestive activity. And since a very
small quantity of ferment can act upon a practically indefinite amount
of material if allowed sufficient time, we can only make comparisons
when the time of digestion and all other conditions are the same. If
we find that a given quantity of one gastric extract, acting on a given
weight of fibrin, dissolves it in half the time required by an equal
amount of another gastric extract, or dissolves twice as much of it in a
given time, we conclude that the digestive activity of the pepsin is twice
as great in the first extract as in the second. But this does not permit
us to say that the one contains twice as much pepsin as the other. For
it has been found that the amount of digestion in a given time is not
directly proportional to the quantity of ferment present, but to the
square root of the quantity of ferment (Schutz's law). This law was
deduced by Schiitz for pepsin, but is said to hold also for trypsin,
steapsin, and ptyalin (Pawlow, Vernon). To determine the amount of
proteolysis the nitrogen of the protein which has gone into solution may
be estimated (p. 521). The following table shows the results of one
experiment :
Digested Nitrogen in Grammes.
Pepsin Solution used
inC.C.
Found.
Calculated.
I
O'O23O
O-Q223
4
0*0427
0*0446
9
0-0686
0^0669
16
0-0889
0^0892
343
Or a piece of a glass capillary-tube filled with heat-coagulated egg-white
may be cut off and placed in the digestive mixture (Mett's tubes). At
the end of the period of digestion the length of the piece of tube and
that of the undigested remnant of the column of coagulated protein
are measured with a millimetre scale under a low- power microscope.
The difference gives the length of the column digested. If i c.c. of
gastric juice caused in a given time digestion of 2 mm. of the egg-white,
4 c.c. of the same juice would digest in the same time and under identical
conditions about 4 mm., and 9 c.c. about 6 mm. As a test of the
activity of a diastatic ferment, we take the amount of sugar formed in
a given time in a given quantity of a standard starch solution. To
determine the activity of a liquid, say, the pancreatic juice, as regards
fat-splitting ferment, the acidity of the emulsion formed by the juice
and fat after standing for a definite time at, a given temperature (with
occasional shaking) can be estimated by titration with baryta solution.
In addition to the ferments of the digestive juices which act extra-
cellularly in the lumen of the alimentary canal, and those which
do their work intracellularly in its walls, micro-organisms are
present in the gut, and even in normal digestion contribute to the
changes brought about in the food ; while under abnormal conditions
they may awaken into troublesome, and even dangerous, activity.
It is now known that these act by producing intracellular enzymes.
It may be noted here, although the subject must be again referred
to (p. 390), that specific substances capable of inhibiting the action
of ferments exist. Some of these antiferments are normally present
in the body — an antitrypsin, for instance, in normal blood-serum.
Numerous antiferments may be artificially obtained by immunizing
animals with the original ferments. Thus an antilipase is found
in the serum of rabbits after injection of pancreatic lipase, and an
antiemulsin after injection of emulsin. Injection of rennin causes
the formation of antirennin, which can be demonstrated in the
blood-serum and milk of the immunized animal. Besides the anti-
ferments, bodies, sometimes spoken of as ' co-enzymes, ' are known
which aid the action of certain enzymes, not in the general way
in which, for instance, increase of temperature up to the optimum
does, but in some quite special manner. Thus, as we shall see,
bile salts greatly facilitate the fat-splitting action of lipase. This
co-operation is not to be confounded with the activation of the
proferment or zymogen which in many cases represents the inactive
form of the enzyme, while it is still within the secreting cells. For,
once activated, the fully formed enzyme cannot be made to revert
to the zymogen stage. For example, the active trypsin of the
pancreatic juice cannot be changed into inactive trypsinogen,
whereas substances which simply co-operate or co-act with enzymes
leave the latter unaltered when they are removed. Thus lipase does
not preserve the increased activity conferred upon it by bile salts
when the bile salts are again separated from the digestive mixture.
It is now necessary to consider in detail the nature of the various?
344
DIGESTION
juices yielded by the digestive glands, and the mechanism of their
secretion. Since it is along the digestive tract that glandular action
is seen on the greatest scale, this discussion will practically embrace
the nature of secretion in general. And here it may be well to say
that, although in describing digestion it is necessary to break it up
into sections, a true view is only got when we look upon it as a
single, though complex, process, one part of which fits into the other
from beginning to end. It is, indeed, the business of the physiologist,
wherever it is possible to insert a cannula into a duct and to drain
off an unmixed secretion, to investigate the properties of each juice
upan its own basis; but it must not be forgotten that in the body
digestion is the joint result of the chemical work of five or six
secretions, the greater number of which are actually mixed together
in the alimentary canal, and of the mechanical work of the gastro-
intestinal walls.
Saliva. — The saliva of the mouth is a mixture of the secretions
of three large glands on each side, and of many small ones. The
large glands are the parotid, which opens by Stenson's duct opposite
the second upper molar tooth; the submaxillary, which opens by
Wharton's duct under the tongue ; and the sublingual, opening by
a number of ducts near and into Wharton's. The small glands are
scattered over the sides, floor, and roof of the mouth, and over the
tongue.
Two types of salivary glands, the serous or albuminous and the
tmtcous, are distinguished by structural characters and by the
nature of their secretion; and the distinction has been extended
to other glands. The parotid of many, if not all, mammals is a
purely serous gland; it secretes a watery juice with a general re-
semblance in composition to dilute blood-serum. The submaxillary
of the dog and cat is a typical mucous gland; its secretion is viscid,
and contains mucin. The submaxillary gland of man is a mixed
gland; mucous and serous alveoli, and even mucous and serous
cells, are intermingled in it. The submaxillary of the rabbit is
purely serous. The sublingual is, in general, a mixed gland, but
with far more mucous than serous alveoli. Some of the small
glands are serous, others mucous in type.
The mixed saliva of man is a somewhat viscous, colourless liquid
of low specific gravity (1002 to 1008, average about 1005), alkaline
to litmus, acid to phenolphthalein, but when tested by the electrical
method (p. 24) almost neutral. Besides water and salts, it contains
mucin (entirely ^rom the submaxillary, the sublingual and the
small mucous glands of the mouth), to which its viscidity is due,
traces of serum-albumin and serum-globulin (chiefly from the
parotid), and a ferment, which hydrolyses starch, and therefore
belongs to the group of amlyases or diastases. It differs somewhat
from the amylase of pancreatic juice. But the small differences
THE CHEMISTRY OF THE DIGESTIVE JUICES
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346 DIGESTION
usually found between ferments of the same kind derived from
different sources may be due to the presence of other substances,
and do not necessarily indicate that the ferments are distinct. For
the present it may be assumed that the amylase of saliva is the
same ferment encountered in the pancreatic juice, and in many,
or all, of the tissues. An oxydase or oxidizing ferment is also
present in saliva. The salts are calcium carbonate and phosphate
(often deposited as ' tartar ' around the teeth, occasionally as
salivary calculi in the glands and ducts), sodium bicarbonate,
sodium and potassium chloride, and almost always a trace of sul-
phocyanide of potassium, detected by the red colour which it strikes
with ferric chloride.* The total solids amount only to five or six
parts in the thousand. A great deal of carbon dioxide can be
pumped out from saliva, as much as 60 to 70 c.c. from 100 c.c.
of the secretion — i.e., more than can be obtained from venous blood.
Only a small proportion of this is in solution, the rest existing as
carbonates. Oxygen is also present even in saliva which has not
come into contact with the air, and, indeed, in somewhat greater
quantity than in serum (about 0*6 volume per cent, in dog's saliva).
Under the microscope epithelial scales, dead and swollen leucocytes
(the so-called salivary corpuscles), bacteria, and portions of food,
may be found. All these things are as accidental as the last —
they are mere flotsam and jetsam, washed by the saliva from the
inside of the mouth. But greater significance attaches to certain
peculiar bodies, either spherical or of irregular shape, that are seen
in the viscid submaxillary saliva of the dog or cat. They appear
to be masses of secreted material. The quantity of saliva secreted
in the twenty-four hours varies a good deal. On an average it is
from i to 2 litres (Practical Exercises, p. 454).
Besides its functions of dissolving sapid substances, and so allow-
ing them to excite sensations of taste, of moistening the food for
deglutition and the mouth for speech, and of cleansing the teeth
after a meal, saliva, in virtue of its ferment, amylase, has the power
of digesting starch and converting it into the disaccharide maltose,
a reducing sugar (Ci^w^u)- ^n man the secretion of any of the
three great salivary glands has this power, although that of the
parotid is most active. In the dog, on the other hand, parotid saliva
has little action on starch, and submaxillary none at all; while in
animals like the rat and the rabbit the parotid secretion is highly
active. In the horse, sheep, and ox, the saliva secreted by all the
glands seems equally inert.
When starch is boiled, the granules are ruptured, and the starch
* In 100 students the saliva only once failed to give the reaction, and in
this individual a trace of sulphocyanide was present 3 days later. It is absent
from the saliva of many animals. In 25 dogs submaxillary saliva obtained
by stimulation of the chorda tympanj only once gave the ferric chloride
reaction, and then faintly.
THE CHEMISTRY OF THE DIGESTIVE JUICES 347
passes into colloidal solution, yielding an opalescent liquid. If a
little saliva be added to some boiled starch solution which is free
from sugar, and the mixture be set to digest at a suitable temperature
(say 40° C.), the solution in a very short time loses its opalescence
and becomes clear. It still, however, gives the blue reaction with
iodine; and Trommer's test (p. 10) shows that no sugar has as yet
been formed. Later on the iodine reaction passes gradually through
violet into red; and finally iodine causes no colour change at all,
while maltose is found in large amount, along with some isomaltose
(p. 338), a sugar having the same formula as maltose, but differing
from it in the melting-point of the crystalline compound formed by
it with phenyl-hydrazine (p. 525). Traces of dextrose, a sugar
which rotates the plane of polarization less than maltose, but has
greater reducing power, may be found among the end-products
when the digestion is conducted in vitro. It is probable that this
is produced from the maltose by another enzyme (maltase), present
in small amount in saliva. In any case it is well known that mal-
tose may be a stage in the hydrolysis of starch to dextrose, and can
be detected among the intermediate products when the starch is
acted on by dilute acid under conditions which permit a gradual
decomposition of the fragments into which the polysaccharide
molecule is successively split. But the observation has also been
made that the saliva itself (in the cat) may contain a trace of dex-
trose (Carlson).
The red colour indicates the presence of a kind, or a group, of
dextrins sometimes called erythrodextrin, because of this colour
reaction; the violet colour shows that at first this is still mixed with
some unchanged starch. Soon the dextrins which give the red colour
disappear, and are succeeded by other dextrins, which give no colour
with iodine, and are therefore called achrodextrins. These are
partly, but in artificial digestion never completely, converted into
maltose, and can always at the end be precipitated in greater or
less amount by the addition of alcohol to the liquid. It is probable
that a whole series of dextrins is formed during the digestion of
starch. But little is known of their chemical nature. Recently,
however, some of these intermediate bodies have been obtained
in crystalline form. One of these appears to be a hexa-amylose —
i.e., it consists of six C6H10O6 groups, and would therefore be
capable of yielding, on the assumption of water, three molecules
of maltose or six of dextrose. This is accordingly a relatively
small fragment of the big original molecule of starch. When the
sugar is removed as it is formed, as is approximately the case when
the digestion is performed in a dialyser, the residue of unchanged
dextrin is less than when the sugar is allowed to accumulate (Lea).
In ordinary artificial digestion, for instance, under the most favour-
able circumstances at least 12, to 15 per cent, of the starch is left
348 DIGESTION
as dextrin; in dialyser digestions the residue of dextrin may be
little more than 4 per cent. This goes far to explain the complete
digestion of starch which takes place in the alimentary canal, a
digestion so exhaustive that, although dextrins may be found in
the stomach after a starchy meal, they do not occur in the intestine,
or only in minute traces. Here the amylolytic ferment of the
pancreatic juice, which is essentially the same in its action as the
amylase of saliva, only more powerful, must effect a very complete
conversion of the starch molecules accessible to its attack. It is
not inconsistent with tliis, that unchanged starch granules may
sometimes be excreted in the fasces, especially when imbedded in
raw vegetable structures. For it may be easily shown that un-
boiled starch is digested by amylase with far greater difficulty than
boiled starch, an illustration of the important part played by
cooking in the preparation of the food for digestion.
It is a notable fact that amylases, also called diastases, are not
confined to the animal body, but are widely distributed in plants.
The polysaccharide starch forms the great reserve of carbohydrate
material in plant nutrition, and is mobilized for the use of the
vegetable cells by being hydrolysed to simple sugars under the in-
fluence of these enzymes, just as the polysaccharide glycogen, the
great carbohydrate reserve of animal nutrition (p. 533), is mobilized
in the form of dextrose under the influence of the diastase of the
liver. A diastase, which is present in all sprouting seeds, and
may be readily extracted by water from malt, forms dextrin and
maltose from starch. The optimum temperature of malt diastase,
however, is about 55° C., while that of ptyalin is about 40° C.
While a neutral or weakly alkaline reaction is not unfavourable
to salivary digestion, it goes on best in a slightly acid medium.
It has been shown that the activity of ptyalin on starch, both
having been previously dialysed to get rid as far as possible of salts,
is increased by the addition of very small amounts of acids and of
the neutral salts of strong monobasic acids. The action is decreased
by larger amounts of acid (0-0007 to 0-0012 per cent, of hydrochloric
acid) and by neutral salts of weak acids. An acidity equal to that
of a o-i per cent, solution of hydrochloric acid stops salivary
digestion completely, although the ferment is still for a time
able to act when the acidity is sufficiently reduced. Strong acids
or alkalies permanently destroy it. These facts indicate that in
the mouth, where the reaction is weakly alkaline, the conditions
are comparatively favourable to the action of the ptyalin. They
are still more favourable in the stomach for some time after the
beginning of a meal, while the reaction is yet weakly acid. It has
been observed that (in cats) salivary digestion may go on for an
hour or more in the cardiac end of the stomach, since free hydro-
chloric acid does not appear here before that time. Since the con-
349
tents of the cardiac end are not freely intermixed with those of the
pyloric end, a greater proportion of sugar is found in the former,
and the difference is more marked with solid than with liquid food
(Cannon and Day). But during the greater part of gastric digestion
the degree of acidity is such that the ptyalin must be hindered.
Although the food stays but a short time in the mouth, there is no
doubt that, in man at least, some of the starch is there changed into
sugar (p. 356)- But this is not the case in all animals. Something
depends on the amylolytic activity of the saliva, and something
upon the form in which the starchy food is taken, whether it is
cooked or raw, enclosed in vegetable fibres, or exposed to free ad-
mixture with the secretions of the mouth.
The fact already mentioned that hydrolytic changes of the same
nature as those produced by enzymes can be brought about in other
ways holds good for the salivary amylase. If starch is heated for
a time with dilute hydrochloric or sulphuric acid, it is changed
first into dextrin, and then into a sugar, which, however, is not
the disaccharide maltose, but the monosaccharide dextrose — that
is to say, the hydrolysis with acid proceeds a step farther than the
hydrolysis in the presence of ptyalin. If maltose is treated with
acid in the same way, it is also changed into dextrose. When
glycogen (p. i) is boiled with dilute oxalic acid at a pressure of three
atmospheres, isomaltose and dextrose are formed (Cremer). Facts
already mentioned, and others to be cited later on, show that the
action of the other digestive ferments can also be imitated by
purely artificial means. Indeed, we may say that the ferments
accomplish at a comparatively low temperature what can be done
in the laboratory at a higher temperature, and by the aid of what
may be called more violent methods.
Gastric Juice. — The Abbe Spallanzani, although not, perhaps,
the first to recognize, was the first to study systematically, the
chemical powers of the gastric juice, but it was by the careful
and convincing experiments of Beaumont that the foundation of
our exact knowledge of its composition and action was laid.
It is difficult to speak without enthusiasm of the work of Beaumont,
if we consider the difficulties under which it was carried on. An army
surgeon stationed in a lonely post in the wilderness that was then
called the territory of Michigan, a thousand miles from a University,
and four -thousand from anything like a physiological laboratory, he
was accidentally called upon to treat a gun-shot wound of the stomach
in a Canadian voyageur, Alexis St. Martin. When the wound healed,
a permanent fistulous opening was left, by means of which food could
be introduced into the stomach and gastric juice obtained "from it.
Beaumont at once perceived the possibilities of such a case for physio-
logical research, and began a series of experiments on digestion. After
a while, St. Martin, with the wandering spirit of the voyagsur, returned
to Canada without Dr. Beaumont's consent and in his absence.
Beaumont traced him, with great difficulty, by the help of the agents
of a fur-trading company, induced him to come back, provided for his
350 DIGESTION
family as well as for himself, and proceeded with his investigations,
A second time St. Martin went back to his native country, and a second
time the zealous investigator of the gastric juice, at heavy expense,
secured his return. And although his experiments were necessarily less
exact than would be permissible in a modern research, the modest book-
in which he published his results is still counted among the classics of
physiology. The production of artificial fistulae in animals, a method
that has since proved so fruitful, was first suggested by his work.
Gastric juice when obtained pure, as it can be from an acci-
dental fistula in man, or, better, by giving a dog with an oesophageal
as well as a gastric fistula a ' sham-meal ' (p. 402), is a clear, thin,
colourless liquid of low specific gravity (in the dog 1003 to 1006)
and distinctly acid reaction. The total solids average about
5 parts per thousand, of which the ash (chiefly sodium and potas-
sium chloride, with small quantities of calcium and magnesium
phosphate) represents about a fourth, and heat-coagulable sub-
stances (proteins, nucleoprotein) about a third. None of these has
any special importance in digestion. Of quite a different significance
are the three ferments present: pepsin, which changes proteins
into peptones; rennin, which curdles milk; and a fat-splitting fer-
ment or lipase which, under certain conditions at least, splits
up emulsified neutral fats — e.g., the fat of milk — into the
alcohol (glycerin) and the fatty acids linked with it, but has so
little action upon non-emulsified fat, that when this is taken into
the stomach, it eventually passes into the duodenum practically
unchanged. The acidity is due to free hydrochloric acid, the other
important constituent of the juice. In the dog the proportion of
this acid varies from 0-46 to 0-58 per cent. In such analyses as
have been made of approximately pure human gastric juice a smaller
percentage of hydrochloric acid has usually been obtained (at most
0-35 to 0-4 per cent.). But there is some reason to believe that if
the human juice could be collected in a faultless manner, and
especially free from any admixture with saliva or with a pathological
secretion of mucus, it would show as high a percentage of acid as
the dog's juice.
In cases of cancer, whether the growth is situated in the stomach
or not, the free hydrochloric acid of the gastric juice is usually
much reduced, and often absent. Under such conditions some
lactic acid may be present in the stomach, being produced from the
carbo-hydrates by the action of bacteria (Bacillus acidi lactici),
which are normally held in check by the hydrochloric acid, although
not rendered incapable of growth when they have passed on into
the intestine. Even in the strength of 0-07 to 0-08 per cent, hydro-
chloric acid prevents the formation of lactic acid from dextrose.
Indeed, when all the hydrochloric acid of the gastric juice is com-
bined with proteins, the protein-acid compound still inhibits the
growth of bacteria in the stomach, although not so efficiently as the
ftt£ blGbStlVE JUICES 351
Same amount of free acid. That in normal gastric juice the acidity
is not due to lactic acid can be shown by shaking the juice with
ether which takes up lactic acid, and then applying Uffelmann's
test to the ethereal extract (Practical Exercises, p. 460)-
More than this, it is not due to an organic, but to an inorganic
acid, for healthy gastric juice causes such an alteration in the
colour of aniline dyes like congo-red and methyl violet as would
be produced by dilute mineral acids, and not by organic acids, even
when present in much greater strength.* Finally, when the bases
and acid radicles of the juice are quantitatively compared, it is
found that there is more chlorine than is required to combine with
the bases; the excess must be present as free hydrochloric acid
In the pure gastric juice of fishes like the dogfish and skate, however,
the acid is said not to be hydrochloric but an organic acid. The
quantity of gastric juice secreted depends upon the nature and
amount of the food. It has been estimated at as much as 5 litres
in twenty-four hours, or several times the quantity of saliva secreted
in the same time. With sham feeding a dog may yield 200-300 c.c.
in an hour.
The great action of gastric juice is upon proteins. In this two
of its constituents have a share, the pepsin and the free acid. One
member of this chemical copartnery cannot act without the other ;
peptic digestion requires the presence both of pepsin and of acid ;
and, indeed, an active artificial juice can be obtained by digesting
the gastric mucous membrane with dilute (0-2 to 0-4 per cent.)
hydrochloric acid. A glycerin extract of a stomach which is not
too fresh also possesses peptic power, the zymogen or mother
substance, pepsinogen, having been activated to pepsin. Free
acid very readily effects this activation, but this is far from being
the only function of the hydrochloric acid, for active pepsin still
requires the addition of a sufficient quantity of acid to render its
proteolytic power available.
Well- washed fibrin obtained from blood is a convenient protein
for use in experiments on digestion; although, of course, for many
purposes only isolated purified proteins can be employed. Since the
blood contains traces of pepsin, the fibrin should be boiled to destroy
any which may be present (see also p. 453).
If we place a little fibrin in a beaker, cover it with gastric juice
obtained from a dog or with 0-4 per cent, hydrochloric acid, to which a
small quantity of pepsin or of a gastric extract has been added, and
put the beaker in a water-bath at 40° C., the fibrin soon swells up and
becomes translucent, then begins to be dissolved, and in a short time
has disappeared (see Practical Exercises, p. 458). If we examine the
* A dilute solution of congo-red is turned violet by organic and blue by
inorganic acids; the gastric juice turns it blue. Methyl violet is rendered blue
by an inorganic acid like hydrochloric acid, and green if more of the acid be
added. It is not altered by organic acids. Gastric juice turns it blue.
35>2 DIGESTION
liquid before digestion has proceeded very far, we shall find chiefly
so-called acid -albumin in solution; later on, chiefly albumoses; and of
these some authors distinguish the primary albumoses (proto -albumose
and hetero-albumose), the first to appear in quantity, followed by
secondary or deutero-albumoses (p. 10).* Still later, peptones in large
and always relatively increasing amounts will be present along with
the albumoses. From this we conclude that acid-albumin is a stage
in the conversion of fibrin into albumose, and albumose a half-way
house between acid -albumin and peptone. It must not be supposed,
however, that all the protein is first changed into acid-albumin before
any of the acid-albumin is changed into albumose, or that all the
protein has already reached the albumose stage before peptone begins
to appear. On the contrary, a certain amount of albumoses and of
peptones are present very early in peptic digestion, while the greater
part of the original protein is still unaltered. • Among the somewhat
vaguely characterized group of bodies comprised under the term
peptones, there are no doubt decomposition products of the proteins
in which the hydrolysis has been carried to different degrees. Similar,
but not identical, intermediate substances occur in the digestion of the
other proteins, including that of bodies like gelatin, which are not
ordinary proteins, but which pepsin can digest. The generic name of
proteose properly includes all bodies of the albumose type, the term
' albumose ' itself being sometimes reserved for such intermediate
products of the digestion of albumin; while those of fibrin are called
fibrinoses; of globulin, globuloses; of casein, caseoses; and so on. The
peptones produced from different proteins are also not absolutely
identical. If the digestion is prolonged, the peptones first formed are
in turn further hydrolysed, so that eventually a considerable proportion
of the original protein is converted into bodies which no longer give the
biuret reaction.
In the stomach, during the four or five hours for which gastric
digestion ordinarily lasts, none of the protein passes beyond the
stage of proteose and peptone, including those relatively simple
' abiuret ' compounds which still consist of several ' building-stones, '
chiefly, it would seem, the amino-acids, phenylalanin, and prolin,
linked together. When precautions are taken to prevent the
passage of any portion of the contents of the duodenum into the
stomach, no amino-acids can be detected in the gastric contents
during the digestion of protein. In this connection it is interesting
to note that none of the polypeptides hitherto prepared (p. 2) are
decomposed by pepsin. It is not known at what points in the link-
age of the groups that compose the complex protein molecule the
pepsin ruptures the chain, but the points of attack are different from
those of trypsin. The pancreatic juice, as we shall see later on, not
* In the light of modern investigation the results of fractional precipitation
by salts of the products of proteolysis have lost a good deal of their interest,
and it is seen that undue importance has often been attached to them. The
student should be warned that such terms as ' albumose ' and ' peptone ' do
not indicate precise chemical differences between the products separated in
this way, nor even invariably such differences in molecular weight as the
current schemata of the digestive processes are apt to imply. Some so-called
' peptones ' may indeed have a higher molecular weight and be more nearly
related to the original protein than some so-called ' albumoses.'
THE CHEMISTRY OF THE DIGESTIVE JUICES 353
only effects a more complete conversion into peptones, but can split
up the whole or a very large proportion of the peptones themselves
into amino-acids and the other ' building-stones ' of the original
protein. Since the subject of protein digestion must come up again,
it will be well to postpone any closer discussion of the process till we
can view it as a whole. In the meantime it is only necessary to
repeat that pepsin alone cannot digest proteins at all. Its action
requires the presence of an acid; in a neutral or alkaline medium
peptic digestion stops. The precise mode of action of the acid is by
no means clear.
Dilute acid alone does not dissolve coagulated proteins like boiled
fibrin, or does so only with extreme slowness. But it causes them to
swell up by imbibition of water, and probably in this way facilitates
the entrance of the ferment. Uncoagulated proteins are readily
changed by acid into acid-albumin ; and by the prolonged action of
acids, especially at a high temperature, further changes of much the
same nature as those produced in peptic digestion may be caused in
all proteins. But under the ordinary conditions of natural gastric
digestion, it may be said that the acid alone does little until it is
aided by the ferment, just as the ferment alone does nothing without
the aid of the acid. The acid enters into a temporary combination
with the protein, the more highly hydrolysed proteins, such as
peptones, combining with a greater proportion of acid than such
proteins as fibrin or albumin. These compounds so easily undergo
hydrolytic dissociation that, in spite of its union with the proteins,
the hydrochloric acid is able to act along with the pepsin, so that
peptic digestion goes on even when enough protein is present to
combine with all the acid. There is some evidence that in the
gastric juice the pepsin exists in the form of an unstable compound
with hydrochloric acid, and it is probably this pepsin-hydrochloric
acid compound which is the actual catalytic agent in peptic digestion.
Although hydrochloric acid acts most powerfully, other acids, such
as nitric, phosphoric, sulphuric, or lactic (arranged in the order of
their efficacy), can replace it.
The Milk-Curdling Action of Gastric Juice. — The milk-curdling
ferment, rennin, or chymosin, is contained in large amount in an
extract of the fourth stomach of the calf, which, as rennet, has long
been used in the manufacture of cheese. It exists in the healthy
gastric juice of man, but disappears in cancer of the stomach and in
chronic gastric catarrh. It has been stated by a number of observers
that the properties of rennin are never found in gastric juice or any
preparation obtained from it or from the gastric mucous membrane
unless pepsin is present. This has suggested that there is no separate
milk-curdling ferment, but that the clotting or precipitation of
caseinogen is merely an associated a.ction of the pepsin. Ferments
of the most varied origin will curdle milk. Pawlow has maintained
354
that the milk-curdling property not only of the gastric juice, but also
of the pancreatic juice and of the secretion of Brunner's glands, is
associated with the proteolytic ferment.
He asserts that when the comparison is instituted under proper
conditions there is an exact parallelism between the proteolytic and
the milk-curdling power of these secretions, no matter what the
circumstances may be in which they are collected, or the influences
to which they are exposed after collection. He has found it im-
possible to separate from any one of them a fraction which has
milk-curdling power without proteolytic power. On the other hand,
the majority of investigators maintain the separate identity of
rennin. Hammarsten especially states that he can destroy the
peptic activity without destroying the milk-curdling power of gastric
extracts, and vice versa. According to Burge, when a solution dis-
playing both peptic and milk-curdling power is electrolyzed, the
pepsin action is abolished at a certain stage, while the rennet action
is unaffected. It would seem, then, that the balance of evidence
is in favour of the separate identity of the rennet enzyme.
However this may be, the curdling of milk by the gastric ferment
includes two processes: (i) An action on caseinogen in the course of
which it acquires new properties, becoming changed into casein.
This substance is not capable of being converted into casein,
and remains in solution in the whey. (2) The altered casein-
ogen or casein combines with soluble calcium salts and in the
presence of these is precipitated as the curd. The change which
occurs in the caseinogen has been the subject of much discussion,
which has not yet led to a definite conclusion. According to some
observers, the change consists in a decomposition of caseinogen, in
the course of which a new substance, whey-protein, not previously
present in the milk, is split off. This substance is not capable of
being precipitated by lime salts, and remains in solution in the whey.
According to others, the molecule of caseinogen is simply changed
into two molecules of casein (van Slyke). Dilute acid will of itself
precipitate caseinogen, and the presence of acid, and particularly
hydrochloric acid, in the gastric juice helps its milk-curdling action.
But that a ferment is really concerned is indicated by the fact that
the juice, after being made neutral or alkaline, still curdles milk, and
that this power is destroyed by boiling. The optimum temperature
is the same as that of the other ferments of the digestive tract, about
40° C. (p. 337). The persistence of the milk-curdling activity in the
presence of OH ions, while for peptic activity free H ions are neces-
sary, is a further and, indeed, a strong argument in favour of the
separate existence of the rennet ferment.
As to the exact function of the milk-curdling ferment of the
gastric juice in digestion, we have no precise knowledge. It seems
superfluous if we suppose that the free acid is able of itself to do all
THE CHEMISTRY OF THE DIGESTIVE JUICES 355
that the ferment does along with it. But there is evidence that the
curd produced by the ferment is more profoundly changed than the
precipitate caused by dilute acids; for the latter may be redissolved,
and then again curdled by rennin in the presence of calcium salts,
while this cannot be done with the former. We may suppose, then,
that the ferment is capable of effecting changes more favourable to
the subsequent action of the pepsin upon the casein than those
which the acid alone would effect. Or it may be that the ferment
acts in the early stages of digestion before much acid has been
secreted. The curdling of milk probably plays a part in ensuring
the retention of this food, the proper digestion of which is all-impor-
tant for the suckling, for a sufficient length of time in the stomach.
Otherwise, like water and watery liquids in general, it would be
rapidly passed into the duodenum. Even if this were not the case,
there is another reason for early curdling. Milk is a very dilute
food, and the immense proportion of water in it might weaken the
gastric juice too much for rapid digestion of the proteins. The
separation of the whey and its prompt escape through the pylorus
would obviate this. But caution should be exercised in giving a
physiological value to all the details of the milk-curdling action of
the gastric juice. Milk-curdling ferments, or, at any rate, ferments
with a milk-curdling influence, have an extremely wide distribution,
both in secretions which in normal circumstances can never come
into contact with milk, and in the tissues of animals and plants.
Many bacteria produce them. And it appears that in the suckling,
where it might be expected, if anywhere, to have a definite and
important office, the rennet action of the gastric juice is distinctly
less than in the adult. It is worthy of note that the curd formed by
rennet from human milk is more finely divided than that formed
from cow's milk, and therefore is more easily digested. The addition
of lime-water or barley-water to cow's milk keeps the curd from
adhering in large masses, and thus aids its digestion — a fact which
is sometimes usefully applied in the artificial feeding of infants.
Gastric Lipase. — On fats gastric juice has usually been supposed
to have no action, although everybody admits that it will dissolve
the protein constituents of fat-cells and the protein substances which
keep the fat-globules of milk apart from each other. It has, how-
ever, been recently shown that both in the stomach and in vitro
(with glycerin extracts of the gastric mucous membrane) a consider-
able amount of well -emulsified fat may be split up, and that this is
due to a ferment which is different in several respects from the
lipase of pancreatic juice. Gastric juice splits up fat, both in
neutral and in weakly acid solutions. The slightest excess of alkali
checks the action. The glycerin extract is much more resistant to
alkali, while very sensitive to hydrochloric acid. This indicates
that the fat-splitting ferment exists in the mucous membrane in a
356
DIGESTION
different form from that in which it exists in the juice — namely, as
a zymogen or mother-substance. But while the zymogen of the
pancreatic lipase is activated by bile, this is not the case with the
mother-substance of the gastric lipase. It appears that in the
suckling the lipase of the gastric juice plays a more important part
than in later life. This is obviously in accordance with the fact that
the specific food of the suckling — milk — contains as an essential con-
stituent a large proportion of emulsified fat. The conditions for
the emulsification of fat do not exist in the gastric juice, and this is
the reason why the gastric lipase has so slight an effect upon un-
emulsified fat, which presents a surface of contact proportionally so
small. In any case the amount of fat hydrolysed in the stomach
under ordinary con litions is small in comparison with the amount
split in the intestine, although it has been shown that with a diet
rich in fat some of the intestinal contents, including pancreatic
lipase, may pass back into the stomach.
As regards the carbo-hydrates, the swallowed saliva will continue
to act on starch in the stomach, so long as the acidity is not too great ;
while the hydrochloric acid of the gastric juice is able to invert cane-
sugar, changing it into a mixture of dextrose and levulose,* and
also, doubtless, to hydrolyse to dextrose a portion of the maltose
formed by the saliva. Altogether, there is no doubt that the pro-
portion of the carbo-hydrates of the food digested in the stomach is
far from insignificant.
The Antiseptic Function of the Gastric Juice. — The stomach, with
its acid contents, forms during the greater part of gastric digestion
a valve or trap to cut off the upper end of the intestine from the
bacteria-infested regions of the mouth and pharynx, and to destroy
or inhibit the micro-organisms swallowed with the food and saliva.
The occasional presence in vomited matter of sarcinae or regularly
arranged groups of micrococci, generally four to a group, shows that
under abnormal conditions the gastric contents are not perfectly
aseptic ; and even from a normal stomach active micro-organisms
of various kinds can be obtained. But upon the whole there is no
doubt that the acidity of the gastric juice is an important check on
bacterial activity during the first part of digestion, and in the upper
portion of the alimentary canal. Koch has shown that the acidity
of the gastric juice of a guinea-pig is sufficient to kill the comma
bacillus of cholera. Normal guinea-pigs fed with cholera bacilli
* These are both reducing sugars, but, as their names indicate, they rotate
the plane of polarization in opposite directions. The specific rotatory power
of levulose is greater than that of dextrose, so that when cane-sugar is com-
pletely inverted, although equal quantities of dextrose and levulose are pro-
duced, the plane of polarization is rotated to the left. Cane-sugar itself rotates
it to the right. The term ' inversion ' has been extended to include the
similar hydrolysis of other sugars of the disaccharide group — e.g., maltose to
dextrose, and lactose to a mixture of dextrose and galactose, even although
the products are not levo-rotatory.
THE CHEMISTRY OF THE DIGESTIVE JUICES 357
were unaffected. But if the gastric juice was neutralized by an
alkali before the administration of the bacilli the guinea-pigs died.
Charrin found, too, that digestion with pepsin and hydrochloric acid
causes an appreciable destruction or attenuation of diphtheria toxin.
Bacteria, like the lactic acid bacillus, which form acid products, may
be less profoundly affected by the acid gastric juice than the putre-
factive bacteria, which, on the whole, form alkalies, and are there-
fore accustomed to an alkaline medium. Yet we have seen that the
growth of even the lactic acid bacillus is very strictly controlled when
the gastric juice contains the normal amount of hydrochloric acid.
It has been supposed by some that this bactericidal action is the
chief function of the stomach, and the question has been asked why
we should attribute any digestive importance to the secretion of that
viscus, since the pancreatic juice can do all that the gastric juice
does, and some things which it cannot do. Further, it has been
shown that a dog may live five years after complete excision of the
stomach, comport himself in all respects like a normal dog, and when
killed for necropsy show every organ in perfect health (Czerny). In
man, too, the stomach has been excised with a successful result.
But if this is to be admitted as evidence against the digestive function
of the stomach, it is just as good evidence against the bactericidal
function, particularly as it has in addition been shown that even
putrid flesh has no harmful effect on a dog after excision of the
stomach, any more than on a normal dog. And, indeed, the reason-
ing is fallacious which assumes that what may happen under ab-
normal conditions must happen when the conditions are normal.
For nothing is impressed more often on the physiological observer
than the extraordinary power of adaptation, of making the best of
everything, which the animal organism possesses. Doubtless a dog
without a stomach will use to the best advantage the digestive fluids
that remain to him ; and the pancreatic juice, with the aid of the bile
and the succus entericus, may be adequate to the complete task of
digestion. So, too, a man from whom the surgeon has removed a
kidney, or a testicle, or a lobe of the thyroid gland, may be in no
respect worse off than the man who possesses a pair of these organs.
But what do we deduce from this ? Not, surely, that the excised
thyroid, or testicle, or kidney was useless, or the gastric juice in-
active, but that the organism has been able to compensate itself for
their loss. Further, it would seem that the fate of the protein or of
part of the protein digested and absorbed by the stomach is different
from that digested and absorbed by the intestine. For after the
operation of gastro-enterostomy (the establishment of an artificial
opening between the stomach and the small intestine through which
the food passes rapidly without having to submit to the challenge
of the pyloric sphincter), the ingested nitrogen is more quickly
eliminated than when the protein is first subjected to full gastric
358 DIGESTION
digestion. So that when the quantity of protein in the food is
increased above that necessary for nitrogen equilibrium (p. 602), none
of the excess is assimilated and stored up, as is the case in a normal
animal (Levin, etc.).
Pancreatic Juice. — Pancreatic juice, bile, and intestinal juice are
all mingled together in the small intestine, and act upon the food,
not in succession, but simultaneously. But by artificial fistulae in
animals they can be obtained separately ; and occasionally some of
them can be procured through accidental fistulae in man. It is said
that under certain conditions, especially when fat or oil is introduced
into the stomach, the pylorus may remain open long enough to
permit the passage of pancreatic juice or bile from the duodenum into
the stomach, and this has been recommended as a practical method
of obtaining these secretions in man.
Human pancreatic juice, as obtained from a fistula, is a clear, only
slightly viscid liquid of distinctly alkaline reaction to litmus. Its
specific gravity is about 1007 to 1010. The total solids constitute
about i'5 or 2 per cent., of which a little less than i per cent, is made
up of inorganic salts, chiefly sodium carbonate, with small quantities
of chlorides. The balance of the solids consists mainly of proteins.
The alkaline reaction is due to the sodium carbonate, and it is
worthy of remark, as showing the important part taken by this
secretion in the neutralization of the chyme, that when titrated
against standard acid the alkalinity of the pancreatic juice is not
much less than the acidity of the gastric juice when titrated against
standard alkali. The quantity of pancreatic juice secreted during
the twenty-four hours in an average man has been estimated at
500 to 800 c.c. from observations on cases of fistula. Probably
under perfectly normal conditions it is greater. A so-called arti-
ficial pancreatic juice can be made by extracting the pancreas with
water or glycerin. Since better methods of obtaining the natural
juice have been developed, these extracts have lost some of their
importance.
Fresh pancreatic juice contains four ferments : (i) Thezymogen or
mother-substance, trypsinogen, of a proteolytic or protein-digesting
ferment, trypsin ; (2) an amylolytic ferment, or amylase ; (3) a fat-
splitting or lipolytic ferment, steapsin ; (4) a milk-curdling ferment.
The question whether the last is a different body from the
proteolytic ferment has been discussed just as in the case of the
gastric rennin (see p. 353). In any case, it cannot be considered as
taking any practical share in digestion, since it can hardly ever
happen that milk passes through the stomach without being curdled.
Trypsinogen has no action upon proteins, but in normal digestion
it is changed into active trypsin by the enterokinase of the intestinal
juice (p. 372). Pancreatic juice collected without contact with
intestinal contents or with the mucous membrane of the intestine
THE CHEMISTRY OF THE DIGESTIVE JUICES 359
does not digest proteins. The same is true of extracts of perfectly
fresh pancreas, but if the pancreas is allowed to stand for a time, the
extracts contain active trypsin, perhaps because some decomposition
product has activated the trypsinogen. Some writers, however,
state that when contamination of the gland with intestinal contents
or contact with the mucosa has been avoided in its removal from
the body, such extracts will remain inactive for months, although
the trypsinogen can at once be activated to trypsin by the addition
of enterokinase.
Trypsin, to a certain extent, corresponds with pepsin in its action
on proteins. But it acts energetically in an alkaline as well as in a
not too acid medium (a very slight amount of digestion may go on in
distilled water) ; and its action, unlike that of pepsin — at least in
digestions of moderate duration — does not stop at the peptone stage,
but goes on rapidly to the production of the amino-acids, the basic
substances arginin, lysin, and histidin, known as the hexone bases,
and most of the other decomposition products obtained by boiling
proteins with dilute acids. The most important of these products,
so far as they have been isolated and identified, are enumerated in
the table on p. 360 (see also pp. 1-3).
As to the chemical nomenclature of these bodies, the student should
refer to his textbook of organic chemistry. It need only be remarked
here, by way of illustration, that when, e.g., leucin is designated as
a-amino-isobutylacetic acid, this indicates that it can be derived from
the fatty acid isobutylacetic acid by the substitution of an amino group,
NH2, for a hydrogen atom in the a-carbon group (see p. 556) of the
fatty acid — i.e., the group next the carboxyl (COOH) group. Thus,
~H3NcH.CH2.CH2.COOH , £§3\CH.CH«.CH.COOH.
CH3/ * ^ <-H3/ ' |
Isobutylacetic acid. Leucin. NH2
When norleucin, an amino-acid found especially in the proteins of
nervous tissue, is termed a-amino-caproic acid, it is indicated that NH2
replaces one H in the aCH2 group of caproic acid (CH3.CH2.CH2.CH2.
CH2.COOH). The long chemical name of isoleucin (a compound also
derived from the proteins of nervous tissue and from some plant proteins}
indicates that in propionic acid,
CH3.CHa.COOH,
0 «
NH2 is introduced into the a group, yielding
CHg.CH.COOH,
ft I
NH2
or amino-propionic acid (alanin); while in the j8 group one H is replaced
by a methyl (CH3) group, and another H by an ethyl (G>H5) giouy,
yielding finally isonuclein :
H*3 \CH.CH.COOH.
NH2
DIGESTION
CHIEF DECOMPOSITION PRODUCTS OF PROTEINS.
MONOAMINO-ACIDS AND THEIR COMPOUNDS.
/Glycin or glycocoll (aminoacetic acid), CH2(NH2)COOH.
Alanin (aminopropionic acid), CH3CH(NH2)COOH.
Serin or oxyalanin (oxyaminopropionic acid),
CH2OH.CH(NH2).COOH.
Valin or aminovalerianic acid, ^3/CHCH(NH2)COOH-
Leucin (a-aminoisobutylacetic acid) £^3^)CHCH2CH(NH2)COOH.
Norleucin («-amino-caproic acid),
CH3.CH2.CH2.CH2.CH(NH2).COOH.
Isoleucin (a-amino-/3-methyl-/3-ethyl-propionic acid),
rH \
^3^>CH.CH(NH2).COOH.
Cystein (a - amino-/3 - thiopropionic acid), CH2 (SH).CH(NH2)COOH,
which is unstable, two molecules of it easily yielding cystin
di-(n-amino-/3-thiopropionic acid) ,
COOH.CH(NH2).CHa.S.S.CH2.CH(NHj).COOH.
fAspartic or aminosuccinic acid, CH(NH2).COOH.
Jen I
CH2COOH.
Q rt I Glutamic or glutaminic acid, C
*—~
•a -si
Prolin (pyrrolidin carboxylic acid).
Oxyprolin (oxypyrrolidin carboxylic acid).
Tryptophane (a-amino-j3-indol-propionic acid),
yNH— CH
\N — C— CH2.CH(NHa).COOH.
Histidin (/J-imidazol-a-aminopropionic acid), C6H9N3O2.
DlAMINO-ACIDS AND THEIR COMPOUNDS.
Lysin (a-amino-€-amino-caproic acid, CH2NH2(CH8)3CH(NH2)COOH.
Arginin (guanidinaminovalerianic acid),
ufa — p/ NH2
\NH CH2 (CH2)2CH (NH2) COOH .
Ammonia (representing the so-called ' amide-nitrogen,' and liberated
from the products of acid hydrolysis of proteins by heating the
mixture after addition of alkali). It has not been shown that
ammonia is itself one of the ' Bansteine ' of the proteins. •
THE CHEMISTRY OF THE DIGESTIVE JUICES 361
In the artificial compounds of two or more amino-acids which have
been synthesized by Fischer and named by him polypeptides (p. 2),
the carboxyl group of one amino-acid is linked with the amino group
of another. For example, a molecule of alanin and a molecule of glycin
form, with loss of a molecule of water, a molecule of alanyl-glycin,
according to the equation
NH2.CHa.CO|pH +H!NH.CH.CH3— H2O= NH2.CH2.CO.NH.CH.CH3.
COOH COOH
Glycin. Alanin. Glycyl-alanin.
Two or more molecules of the same amino-acid can be linked in the
same way; e.g., two molecules of glycin yield a molecule of glycyl-glycin,
and so on. It has been proved that polypeptides identical witn some of
these synthetic bodies are present in the peptone mixtures derived from
the native proteins, so that it must be assumed that one of the ways
at least in which amino-acids are linked in the protein molecule is that
described.
It has been suggested that the early appearance of some of these
amino-acids in pancreatic digestion is not really due to trypsin, but
to other ferments, peptases, which act upon the peptones formed by
the trypsin. There is, however, no clear evidence of the existence
of a separate peptone-splitting enzyme in pancreatic juice, like the
erepsin of intestinal juice, and it is therefore most natural to suppose
that under the influence of trypsin the protein molecule breaks at
different points from those at which it ruptures under the influence
of pepsin.
After the most prolonged artificial digestion with trypsin, a
residue of the protein remains unconverted into these relatively
simple substances. But even this small portion of the original
protein has undergone a great change, for it no longer gives the
biuret reaction. It can be split into amino-acids, etc., by heating
with acid, and also by the action of the erepsin of the intestinal juice,
and then yields mainly prolin and phenylalanin, substances which
are generally not to be detected among the decomposition products
of protein after digestion with pancreatic juice. This illustrates the
important fact that some of the ' building stones ' of the protein
molecule can be separated from it with far greater ease than others.
Tyrosin, tryptophane, and cystin appear very early in the digestive
fluid, and tyrosin, as shown in the following example from Abder-
halden, may be completely liberated at a time when glutaminic acid
is scarcely more than beginning to appear.
The plant protein edestin, obtained from cottonseed, was digested
with pancreatic juice or an extract containing trypsin. The quan-
tities of tyrosin and glutaminic acid liberated at different periods
of the experiment are expressed as percentages of the total amounts
of these substances contained in the edestin.
362
DIGESTION
Duration of Digestion :
i Day.
2 Days.
3 Days. : 7 Days, j 16 Days.
Tyrosin
Glutaminic acid
78-4
4' 3
97'6
7*4
97'6
io'9
100
3ri
IOO
60' 2
When trypsin ads upon protein already digested by pepsin, this
partially hydrolysed residue is smaller than when the trypsin acts
alone, no matter for how long a time. Also the decomposition of
a given quantity of protein by trypsin is accomplished in a notably
shorter time if it has been previously subjected to the action of
pepsin. This illustrates the co-operative relation of these two
ferments — a relation still more clearly implied in the fact that,
although trypsin readily forms albumoses and peptones from native
protein when such is offered to it, yet in natural digestion the great
albumose- and peptone-forming ferment is pepsin. In the lumen of
the intestine the trypsin is confronted mainly with protein already
hydrolysed to the albumose and peptone stage in the stomach. In
other words, instead of the very large molecules of the original
protein food with a weight of perhaps 5,000 to 7,000, the trypsin
begins its action on a much larger number of much smaller molecules
of only one-twentieth the initial weight or less. The statement is
sometimes made that trypsin is a stronger proteolytic ferment than
pepsin. This may be true in the sense that trypsin carries the de-
composition down to bodies of smaller molecular weight than pepsin.
But within the range of its hydrolytic action pepsin decomposes
certain proteins and allied bodies more readily than trypsin — e.g.,
the serum proteins, and especially elastin and the constituents of
connective tissue.
In all that we have hitherto said regarding tryptic digestion we
have supposed that putrefaction has been entirely prevented — e.g.,
by the addition of toluol. If no antiseptic is added to a tryptic
digest, it rapidly becomes filled with micro-organisms, and emits a
very disagreeable faecal odour ; and now various bodies which are not
found in the absence of putrefaction make their appearance, such as
indol, skatol, and other substances, to which the fascal odour is due.
They are not true products of tryptic digestion, but are formed by
the putrefactive micro-organisms, which can themselves split off
from proteins numerous decomposition products, including tyrosin,
and change tyrosin into indol.
Amylase or pancreatic amylase, the diastatic or sugar- forming
ferment of pancreatic juice, changes starch into dextrin and maltose,
just as the ptyalin of saliva does. The two ferments are possibly
identical, but under the conditions of action of the pancreatic juice
its diastatic power is greater than that of saliva, and it readily acts
THE CHEMISTRY OF THE DIGESTIVE JUICES 363
on raw starch as well as boiled. Pancreatic amylase is mainly,
perhaps entirely, present in the juice in the form of active ferment.
If a zymogen stage exists, the mother-substance is less stable or less
easily extracted from the gland than is trypsinogen. In this respect
amylase also resembles ptyalin. A small amount of maltase is
contained in pancreatic juice, and further hydrolyses to dextrose a
portion of the maltose formed by the amylase.
Steapsin or pancreatic lipase splits up neutral fats into glycerin and
the corresponding fatty acids. The latter unite with the alkalies of
the pancreatic juice and the bile to form soaps. In this important
process bile acts as the helpmate of pancreatic juice; together they
effect much more than either or both can accomplish by separate
action. Many tissues contain fat-splitting ferments or Upases, some
of which are perhaps identical with the pancreatic lipase. The lipase
exists as active ferment in the pancreatic j uice, but there is reason
to believe that a portion of it may be present as a zymogen in the
gland, and probably in the secretion as well. It is changed Jnto
active ferment by the bile salts. Active lipase can also be extracted
from the pancreas by glycerin or water. It is to be noted that it is
only the proteolytic enzyme which is totally inactive till it reaches
the intestine. The significance of this will be discussed later on.
Bile. — Bile is a liquid the colour of which varies in different groups
of animals, and even in the same species is not constant, depending
on the length of time the fluid has remained in the gall-bladder and
other circumstances. When it is recognized that the colour is due
to a series of pigments, which are by no means stable, and of which
one can be caused to pass into another by oxidation or reduction,
this want of uniformity will be easily intelligible. The fresh bile of
carnivora is golden-red. The bile of herbivorous animals is in
general of a green tint, but, when it has been retained long in the
gall-bladder, may incline to reddish-brown. Fresh human bile, as
it flows from a fistula just established, is of a reddish-brown, golden-
yellow or yellow colour. Beaumont speaks of the yellowish bile
which he could press into the stomach of St. Martin by manipulating
the abdomen. In a case observed by the writer, it was seen that
when the bile flowing from a fistula was allowed to spread out in a
dressing, it became greenish, because of oxidation of a part of the
bilirubin to biliverdin, although as it actually escaped from the fistula
it was yellow. The bile of a monkey taken from the gall-bladder
immediately after death is dark green, but if left a few hours in the
gall-bladder it is brown, the green pigment having been reduced. It
should be remembered that human bile from the post-mortem room
may alter its colour in the interval which must elapse before it can
usually be procured after death. Bile, as obtained from fistulse in
otherwise healthy persons, has a specific gravity of about 1008 to
lo 10. In the gall-bladder water is absorbed from the bile and
DIGESTION
mucin added to it, so that the specific gravity of bladder bile is as
high as 1030 to 1040. The reaction is feebly alkaline to litmus.
The composition of two specimens of human bile — one from a fistula,
the other from the gall-bladder — is shown in the following table :
Bladder Bile.
Fistula Bile.
Water -
898-1
977*4
Solids -
101-9
22'6
Mucin and other substances insoluble
in alcohol
I4'5
2-3
Sodium taurocholate and sodium
glycocholate
56-5
IO-I
Inorganic salts ...
6-3
8-5
Fat )
Lecithin }- -
30-9
0-05
CholesterinJ
0-56
The substance which renders bladder bile viscid, but which is present
in much smaller amount in bile from a fistula, and is probably entirely
absent from the fluid as it is secreted by the liver-cells, is commonly
termed 'mucin.' It has been shown, however, that in many animals —
for example, the ox, dog, sheep, etc. — the substance is not a true mucin.
It does not yield, like mucin, on boiling with dilute acid, a carbo-
hydrate group (viz., glucosamine, C6HuO5Nll2, corresponding to
dextrose in which OH is replaced by NH2). It is relatively rich in phos-
phorus, and consists — mainly, at any rate — of a phospho-protein (p. 2).
The mucilaginous substance of human bile consists largely of true mucin.
Mucin is scarcely to be looked upon as an essential constituent of
bile ; it is not formed by the actual bile-secreting cells, but by mucous
glands in the walls and goblet-cells in the epithelial lining of the larger
bile-ducts, and especially of the gall-bladder.
Bile-Pigments. — It has been said that these form a series, but only
two of the pigments of that series are present in normal bile, bilirubin,
and biliverdin. In human bile, the former, in herbivorous bile and
that of some cold-blooded animals, such as the frog, the latter is the
chief pigment. But bilirubin can be extracted in large amount from
the gall-stones of cattle ; while the placenta of the bitch contains bili-
verdin in quantity, although, as in all carnivora, it is either absent
from the bile or exists in it in comparatively small amount. These
facts show that the two pigments are readily interchangeable, but there
is no question that bilirubin is the pigment which is formed by the
liver-cells.
Bilirubin (C32H36N4O6) can be prepared from powdered red gall-
stones by dissolving the chalk with hydrochloric acid, and extracting
the residue with chloroform, which takes up the pigment. From this
solution, on evaporation, or from hot dimethyl anilin, beautiful rhombic
tables or prisms of bilirubin separate out.
Biliverdin (C32H36N4O8) can be obtained from the placenta of the
bitch by extraction with alcohol. It is insoluble in chloroform, and by
means of this property it may be separated from bilirubin when the two
happen to be present together in bile. Biliverdin can also be formed
from bilirubin by oxidation. By the aid of active oxidizing agents,
THE CHEMISTRY OF THE DIGESTIVE JUICES 365
such as yellow nitric acid (which contains some nitrous acid), a whole
series of oxidation products of bilirubin is obtained, beginning with
biliverdin, and passing through bilicyanin, a blue pigment, and other
intermediate bodies, to choletelin, a yellow substance. It is question-
able whether these are all definite compounds. This is the foundation
of Gmeliris test for bile-pigments (see Practical Exercises, p. 462)- The
same colours are produced, and in the same order, when a solution of
bilirubin in chloroform is treated with a dilute alcoholic solution of iodine .
The positive pole of a galvanic current causes the same oxidative
changes, the same play of colours, while the reducing action of the
negative pole reverses the effect, if the action of the positive electrode
has not gone too far. These reactions can also be used for the detection
of bile -pigments.
By the reducing action of sodium amalgam on bilirubin, hemi-
bilirubin (C33H44N4O6) is obtained. It gives a beautiful red colour with
^-dimethylaminobenzaldehyde (Ehrlich's reaction). Hemibilirubin is
identical with the urobilinogen of urine from which urobilin is derived.
Urobilinogen and urobilin (often called in this connection stercobilin)
are also found in the faeces from birth onwards, although not in the
meconium (p. 424). Urobilinogen is derived from the normal bile-
pigment by reduction in the intestine itself, where reducing substances
due to the action of micro-organisms are never absent in extra -uterine life .
The bile of most animals shows no characteristic absorption spectrum.
But the fresh bile of certain animals, the ox, for instance, does show
bands. These, however, are not due to the normal bile-pigment, and
they are not essentially changed when this is oxidized or reduced by
electrolysis. MacMunn attributes the spectrum of the bile of the ox
and sheep to a body which he calls cholohaematin, and which does not
belong to the bile-pigments proper.
The Bile-Salts. — These are the sodium salts of certain acids, of which
glycocholic and taurocholic are the chief. In the bile of omnivora,
including man, both are in general present, and in various proportions;
in human bile there is more glycocholic than taurocholic acid; some-
times taurocholic acid is entirely absent. In the bile of many carnivora
— e.g., the dog and cat — only taurocholic acid is found; in that of the
carnivora generally it is by far the more important of the two acids.
In the bile of most herbivora there is much more glycocholic than
taurocholic acid. The bile acids are paired acids: glycocholic acid
(better named cholyl-glycin) formed by the union of glycin and cholic
acid, and taurocholic acid (or cholyl-taurin), consisting of cholic acid
united with taurin.
The decomposition of the bile-acids into these substances is effected
by boiling them with dilute acid or alkali, a molecule of water being
taken up; thus —
06 + H20 = CH2 (NHa) .COOH + C24H40O6 ;
Glycocholic acid. Glycin. Cholic acid.
C26H45NS07 + H20 = CH2(NH2).CH2.S02.OH + C24H40O5.
Taurocholic acid. Taurin. Cholic acid.
A notable difference between glycocholic and taurocholic acid is that
the latter contains sulphur. The whole of this belongs to the taurin.
Both glycin and taurin are derived from the disintegration of proteins.
We have already seen that among the products of protein hydrolysis a
sulphur-containing body, cystein, which is readily changed into cystin,
is found, and there is good evidence that taurin is derived from cystein
or cystin. In certain pathological conditions cystui appears in the
urine (cysfcinuria). The source of the chohc acid which goes to form
the bile acids is unknown, but it has been surmised that it may be
derived from cholesterin. Thus,
[CH2.SH+3O CH2.SO2.OH CH2.SOa.OH
CH.NH2 = CH.NH2 = CH.NH2
COOH COOH— CO2
Cystein. Cysteinic acid. Taurin.
Traces of cholic acid, formed by hydrolysis from the bile-acids by
the action of putrefactive bacteria, are found in the intestines, especially
in the lower portion.
Pettenkofer s test for bile-acids (Practical Exercises, p. 462), acciden-
tally discovered in examining the action of bile upon sugar, depends upon
three facts: (i) That cholic acid and furfuraldehyde give a purple colour
when brought together; (2) that the bile-salts yield cholic acid when
acted upon by sulphuric acid ; (3) that when cane-sugar is decomposed
by strong sulphuric acid, furfuraldehyde is formed.
Since a similar colour is given when the same reagents are added to a
solution containing albumin, it is necessary to remove this, if present,
from any liquid which is to be tested for bile-acids.
Lecithin and cholesterin, or cholesterol, are by no means peculiar to
bile (p. 4). They are very widely distributed in the body. Lecithin
(C44^oNPO9) belongs to the group of phosphatides, fat-like phosphorus-
containing substances present in all cells. It is a compound of glycerin
with two molecules of fatty acid and one of phosphoric acid. The
phosphoric acid is at the same time united with a base cholin (C6H15NO2) .
The fatty acid (stearic, palmitic, oleic, etc.) varies in different varieties
of lecithin . Heated with baryta-water, lecithin yields the corresponding
fatty acid in the form of a soap, along with cholin and glyceryl-phos-
phoric acid. Glyceryl-phosphoric acid can be further split so as to
yield a molecule of glycerin and one of phosphoric acid.
Cholesierin is a substance with the empirical formula C^I^gO. It
contains an alcohol group in virtue of which fatty acids can be linked
to it, forming esters. It is best obtained from white gall-stones, of
which it is the chief, and sometimes almost the sole constituent (see
Practical Exercises, p. 463).
All the compounds related to cholesterin are grouped together under
the name of sterins. The sterins are very widely distributed both in
animals (zoosterins) and in plants (phytosterins) . Every cell seems to
contain sterins and sterin esters (compounds of the same nature as the
compounds of fatty acids with the alcohol glycerin which constitute the
neutral fats) . In the vertebrates cholesterin and its product: constitute
the chief, perhaps the only sterins, but in invertebrate animals and
plants there is a much greater variety of these substances.
The chief inorganic salts of bile are sodium chloride, sodium carbonate,
and alkaline sodium phosphate. The phosphoric acid of the ash comes
partly from the phosphorus of organic compounds (lecithin and bile-
mucin), the sulphuric acid from the sulphur of taurocholic acid, the
sodium largely from the bile-salts. Iron is a notable inorganic con-
stituent of bile, although it exists only in traces, in the form of phosphate
of iron. Manganese is also present in minute amount. 100 c.c. of
fresh bile yields 50 to TOO c.c. of carbon dioxide, part of which is in
solution and part combined with alkalies.
THE CHEMlSTRy OF THE DIGESTIVE J VICES 367
The quantity of bile secreted in twenty-four hours in an average
man is probably from 750 c.c. to a litre. In nine cases of fistula ol
the gall-bladder in patients operated on for gall-stones or echino-
coccus the daily quantity varied from 500 to 1,100 c.c. (Brand).
Digestive Functions of Bile. — The great action of the bile in
digestion is undoubtedly the preparation of the fats for absorption.
In this preparation four processes are important: two chemical
actions, hydrolysis of neutral fats to glycerin and fatty acids, and
saponification, or the formation of soaps by the union of fatty acids
with bases, especially sodium ; and two physical processes, emulsifi-
cation, or the formation of a mechanical suspension of such fine
globules of unaltered neutral fat as exist in milk, and solution of
soaps and fatty acids. While there has been much discussion as to
the relative share taken by these processes, and especially by saponi-
fication and emulsification in the absorption of fat (p. 441), there is
no doubt that they are all concerned in the digestion of fat or the
preparation of it for absorption and assimilation. In this, indeed,
the processes are complementary to each other, for an essential pre-
liminary to emulsification in the intestine seems to be the format-ion
of a certain amount of soaps, soluble in the intestinal contents, while
the formation of an emulsion enormously increases the surface of
contact between the unaltered fat and the digestive juices, and so
favours more rapid hydrolysis, saponification, and solution. In the
whole series of changes the bile plays a part, though not an indepen-
dent one; it acts always in conjunction with the pancreatic juice.
While no complete explanation has been given of the precise
nature of this partnership, it is certain that the fat-splitting ferment
of the pancreatic juice on the one hand, and the bile-salts on the
other, contribute largely to the total action. An alkaline solution,
a solution of sodium carbonate, e.g., is unable of itself to emulsify
a perfectly neutral oil ; but if some free fatty acid be added, emulsifi-
cation is rapid and complete (p. 12). Now, there is no doubt that
here a soap is formed by the action of the alkali on the fatty acid,
and there is equally little doubt that the formation of the soap is an
essential part of the emulsification. But it is not clear in what
manner the soap acts, whether by forming a coating round the oil-
globules, or by so altering the surface-tension, or other physical
properties of the solution in which it is dissolved, that they no longer
tend to run together. However this may be, in pancreatic juice we
have the two factors present which this simple experiment shows
to be necessary and sufficient for emulsification ; we have a ferment
which can split up neutral fats and set free fatty acids, and an alkali
which can combine with those acids to form soaps. Accordingly,
pancreatic juice is able of itself to form emulsions with perfectly
neutral oils. It is possible that the protein constituents of pancreatic
juice may have a share in emulsification, since the addition of protein
368 DIGESTION
— e.g., egg-white — to a soap solution increases the stability of the
emulsions formed by the soap. In bile, on the contrary, although
the alkali is present, there is no fat-splitting ferment, and, according
to the best experiments, bile alone has no emulsifying power on
perfectly neutral fat. But we now come to a remarkable fact: this
inert bile when added to pancreatic juice greatly intensifies its
emulsifying action, and a solution of bile-salts has much the same
effect as bile itself. The fact is undoubted, but the explanation is
obscure. What it is that the bile or bile-salts can add to the
pancreatic juice which so increases its power of emulsification, we do
not know. It has been surmised that a characteristic physical
property of bile, the diminution of the surface-tension of watery
liquids to which it is added, may play an important part, perhaps,
in enabling the fat-splitting ferments or the emulsifying soaps to get
into closer contact with the unaltered fat. It is also true that
bile, presumably in virtue of the chemical action of its alkaline
salts, can, in presence of a free fatty acid, rapidly form an emulsion.
But the pancreatic juice itself contains so considerable a quantity of
sodium carbonate that it would scarcely seem to require the rela-
tively feeble reinforcement of the alkaline salts of the bile.*
An important part of the effect of the bile is certainly due to its
favouring the fat- splitting action of the pancreatic juice. By the
addition of bile, the quantity of fat split up by a definite amount of
dog's pancreatic juice may be increased two to threefold. It has
been shown that this is an action of the bile-salts. The sodium
salts of synthetically-obtained glycocholic and taurocholic acids
produce the same effect. It is in virtue of this action that the bile-
salts are sometimes spoken of as the co-ferment of the lipase. As
already pointed out, this action is exerted in presence of the fully
formed enzyme, and should not be confounded with the effect of the
bile-salts in activating the lipase zymogen. The capacity of dis-
solving soaps, which is a property of the bile-salts, is also of great
importance in supplementing the solvent power of the intestinal
liquids for the products formed by the pancreatic juice. The
solution of soaps in the bile- salts has the power in its turn of dis-
solving free fatty acids. The significance of this in fat absorption
will be referred to again. A further illustration of the mutual
adaptation of the various digestive juices, of the remarkably precise
manner in which the action of each dovetails into the action of
others, is afforded by the facts already mentioned in connection with
the lipase of the stomach. It is highly probable that the fatty acids
formed by the gastric lipase, even if formed only in small amount,
may exertan important influence in emulsifying the fat as soon as it
enters the intestine. The intestinal juice itself also unquestionably
takes a share in the digestion of fat along with the pancreatic
* It has lately been shown that bile-salts accelerate the formation of soap
from oleic acid by sodium bicarbonate (Kingsbury).
THE CHEMISTRY OF THE DIGESTIVE JUICES 369
secretion and the bile. There exists also, as will be seen later on, a
certain adaptation between the food and the digestive secretions.
Not the best illustration of this, but one which suits the present topic,
is the fact that the food itself probably always contains some free
fatty acids when it contains fat at all. Although our knowledge of
the mutual action of the pancreatic juice and the bile on the digestion
of fats is still incomplete, there is no doubt that they are equally
necessary. For in some diseases of the pancreas fat or fatty acid
often appears in the stools, and this token of imperfect digestion of
the fatty food may be confirmed by the wasting of the patient. The
same may occur when the bile is prevented by obstruction of the
duct or by a biliary fistula from entering the intestine. Yet in some
cases of fistula, where there is every reason to believe that all the bile
is escaping externally, the nutrition of the patient — at any rate, on a
diet not abnormally rich in fat — is unaffected. The mere deficiency
of bile in the intestine is, of course, complicated in obstructive
jaundice by the harmful effects of the biliary constituents circulating
in the blood.
The white stools of jaundice owe their colour, not merely to the
absence of bile -pigment, but also to the presence of fat. Their highly
offensive odour used to be adduced as evidence that bile is the ' natural
antiseptic ' of the intestine. It seems rather to be due to the coating
of the particles of food with undigested fat, which shields the proteins
from the action of the digestive juices, while permitting the putrefactive
bacteria to revel in them unchecked. As a matter of fact, the bile
itself has little, if any, power of hindering the growth of micro-organisms,
although the free bile-acids are tolerably active antiseptics. In suckling
children it is not uncommon to see the faeces white with fat. This is a
less serious symptom than in adults, and perhaps betokens merely that
the milk in the feeding-bottle is undiluted cow's milk, which is richer
in fat than human milk, and ought to be mixed with water.
Bidder and Schmidt found that the chyle in the thoracic duct of a
normal dog contained 3-2 per cent, of fat. In a dog with the bile-duct
ligatured the proportion fell to 0-2 per cent. It is an instance of the
extraordinarily exact adaptation of the digestive juices to the nature
of the food, the mechanism of which will present itself for discussion
later on, that the reinforcing action of the bile upon the fat-splitting
ferment of the pancreatic juice is said to be greater when the food is
rich in fat (p. 414).
Bile has been credited with a physical power of aiding the passage
of fat through membranes moistened with it by diminishiiig the surface
tension, and it has been inferred that this has an important bearing
on the absorption of fat from the intestine. But the inference does
not follow from the statement, and the statement has been itself
denied. There is at present no evidence that the digestive function
of the bile extends beyond the preparation of the food for absorption
to the preparation of the mucosa for absorbing it.
On proteins bile has either no digestive action, or only a feeble
one. Fibrin is slightly digested by the bile of the dog and of man.
But the addition of it to fresh pancreatic juice considerably increases
the proteolytic power of that secretion (Rachford), although not so
decidedly as in the case of the fat-splitting action. The amylolytic
370 DIGESTION
action of the pancreatic juice is also favoured by the bile, and in
about the same degree as its proteolytic effect. Although bile some-
times exerts by itself a feebly amylolytic action, this is not to be
included among its specific powers, for a diastatic ferment in small
quantities is widely diffused in the body.
The addition of bile or bile-salts to a gastric digest causes the
precipitation of any unaltered native protein, acid-albumin, albu-
mose, and pepsin. The precipitate, which is a salt-like compound
of protein with taurocholic acid, is redissolved when the liquid is
rendered alkaline, and therefore in excess of bile, or of a solution of
bile-salts, but the pepsin has no longer any power of digesting
proteins. Pait of the bile-acids and bile-mucin is also thrown down
by the acid of the digest. It has been suggested that by thus
precipitating the constituents of the chyme which have not been
carried to the peptone stage bile prepares them for the action of the
pancreatic juice. But it is difficult to see how the precipitation of
a substance can prepare the way for its digestion, and it is more
probable that if any physiological value is to be given to this reaction,
it has the function of preventing the absorption of proteins which
have not been sufficiently split up. There is little doubt, however,
that the rendering of the pepsin inactive has physiological signifi-
cance, for pepsin exerts an injurious influence upon the ferments of
the pancreatic juice. In digestion, then, the bile has a twofold func-
tion, favouring greatly the activity of the pancreatic ferments, especially
the fat-splitting ferment, and aiding in establishing the conditions
necessary for the transition of gastric into intestinal digestion.
Succus Entericus. — This is the name given to the special secretion
of the small intestine, which is supposed to be a product of the
Lieberkuhn's crypts or intestinal glands. In order to obtain it pure,
it is of course necessary to prevent admixture with the bile, the pan-
creatic juice, and the food. This can be done by dividing a loop of
intestine from the rest by two transverse cuts, the abdomen having
been opened in the linea alba. The continuity of the digestive tube
is restored by stitching the portion below the isolated loop to the
part above it. One end of the loop is sewed into the lips of the
wound in the linea alba, and the other being closed by sutures, the
whole forms a sort of test-tube opening externally (Thiry's fistula).
Or both ends are made to open through the abdominal wound (Vella's
fistula). Another method is to make a single opening in the intes-
tine, and by means of two indiambber balls, one of which is pushed
down, and the other up through the opening, and which are after-
wards inflated, to block off a piece of gut from communication with
the rest. Or several openings may be made at different levels in the
intestine, each being allowed to heal into a wound in the abdominal
wall. When pure juice is required it is collected from the lower
fistulae, while the upper fistulae are opened to permit the escape of the
THE CHEMISTRY OF THE DIGESTIVE JUICES 371
secretions which enter the higher portions of the alimentary canal
(gastric juice, pancreatic juice, and bile). The intestinal juice so
obtained is a thin yellowish liquid of alkaline reaction, generally
somewhat turbid from the presence of a certain number of leucocytes
and epithelial cells. Its specific gravity is about 1010, the total
solids about 1-5 per cent. It contains a small amount of proteins,
including serum albumin and serum globulin, and about the same
proportion of inorganic salts as most of the liquids and solids of the
body, namely, 0-7 or 0-8 per cent., chiefly sodium carbonate and
sodium chloride; but, like the other digestive liquids, it is adapted
to the nature of the food, and therefore its composition is not quite
constant. Like bile, intestinal juice acts but feebly on the food
substances by itself, and if we contented ourselves with examining
the pure and isolated secretion, we should greatly underestimate its
importance. The sodium carbonate, in which it is relatively rich,
will, to be sure, form soaps with fatty acids produced by the action
of the pancreatic juice or of the fat-splitting bacteria in which the
intestine abounds, and thus aid in the digestion of fats. A lipase,
feebler than that of the pancreatic juice, or present in smaller con-
centration, is also a constituent of the succus entericus. That a
great deal of fat may be split up in the alimentary canal in the
absence both of bile and pancreatic juice is well ascertained. The
alkali of the succus entericus must at the same time aid in neutraliz-
ing the original acidity of the chyme, and in preserving the proper
reaction of the intestinal contents. A ferment called invertase, or
sucrase — which is not introduced with the food or formed by bacterial
action as has been suggested, since it occurs in the aseptic intestine
of the new-born child — will invert cane-sugar. The ferments maltase
and lactase will cause a corresponding change in maltose and lactose
(see footnote, p. 356). It is worthy of remark that these inverting
enzymes are present in the intestinal mucosa as well as in the
intestinal juice, and extracts of the mucosa are usually distinctly
more active than the juice itself. So that there is reason to believe
that hydrolysis of the disaccharides may take place both in the
lumen of the gut before absorption and in the wall of the gut during
absorption. Inverting enzymes appear in the intestine early in
embryonic life. Maltase is the most generally distributed of all
these enzymes, and it is found along with lactase in the intestine of
the embryo pig, while invertase is missing till after birth (Mendel).
On native proteins and starch the isolated succus entericus has little
or no action. But it contains a ferment, erepsin, which, although it
does not affect native proteins like serum- and egg-albumin (fibrin
and caseinogen may be slightly digested), exerts a powerful action
on the first products of protein hydrolysis, albumoses, and peptones,
breaking them up into bodies which no longer give the biuret re-
action (ammonia, mono-amino acids, hexone bases, etc.). It
37*
DIGESTION
destroys the diphtheria toxin, which is also rendered innocuous by
trypsin. Erepsin, however, is not specific to the secreted intestinal
juice, for it occurs also, not only in the mucous membrane of the
intestine, which, indeed, contains a greater quantity of it than the
succus entericus, but in all animal tissues hitherto investigated. It
is said even to be sometimes present in pancreatic juice, since in-
activated pancreatic juice, which does not digest other proteins, will
sometimes digest casein. But the matter is far from being settled,
and the presence of erepsin in the pancreatic tissue is a complicating
circumstance. For under abnormal conditions, most glands pro-
vided with artificial fistulae have an increased liability to injuries
of various kinds, which might permit constituents not normally
present in the secretion to pass into it from the cells. The kidney in
mammals is even richer in erepsin than the intestinal mucous
membrane. Next to these come the pancreas, spleen, and liver,
then at a long interval the heart muscle, while skeletal muscle and
brain-tissue are poorest of all in the ferment. The intestinal mucosa
varies in its erepsin content at different levels and on different diets.
In cats on a meat or a mixed diet the duodenum is about five times
richer in the ferment than the stomach. The ileum is about half as
rich as the duodenum, and the jejunum occupies an intermediate
position between the duodenum and ileum (Vernon). The secretion
of Brunner's glands in the duodenum, which resemble in structure
the pyloric glands of the stomach, digests coagulated albumin,
although its proteolytic powers are feebler than those of the pan-
creatic juice.
Enterokinase. — The most characteristic constituent of succus
entericus is a ferment, enterokinase, which differs from all the fer-
ments we have hitherto described in acting not directly upon the
foodstuffs, but upon the trypsinogen of the pancreatic juice, chang-
ing it into the active enzyme trypsin. It may therefore be spoken of
as a ferment of ferments. It has been previously stated that freshly
secreted pancreatic juice is without action upon proteins. The
addition of succus entericus immediately confers upon it a high
degree of proteolytic power. In one experiment pancreatic juice,
obtained by a temporary fistula, required four to six hours to dissolve
fibrin, and did not attack coagulated albumin even in ten hours.
On addition of succus entericus, the same pancreatic juice dissolved
fibrin in three to seven minutes, and rapidly digested coagulated
albumin (Pawlow). In like manner a glycerin extract of a fresh
pancreas has hardly any effect on proteins; a similar extract of a
stale pancreas is active. The fresh pancreas contains trypsinogen,
which is soluble in glycerin, for the inert extract becomes active
when it is treated with dilute acetic acid, or even when it is diluted
with water and kept at the body-temperature. If the fresh pancreas
be first treated with dilute acetic acid, and then with glycerin, the
THE CHEMISTRY OF THE DIGESTIVE JUICES 373
extract is at once active. The trypsinogen can therefore be activated
within the pancreatic cells, gradually when the pancreas is simply
allowed to stand after excision, more rapidly in presence of the dilute
acid. The ordinary tests for ferment action (destruction by boiling,
activity in very small amounts, etc.) have shown that this property
of the intestinal juice is due to a ferment, although it differs in
certain respects from most ferments — -for instance, in requiring a
relatively high temperature to inactivate it. The smallest trace
of enterokinase will convert a large quantity of trypsinogen into
trypsin if time be given. At the same time, although to a much
smaller extent, the fat-splitting and starch-digesting activity of the
pancreatic juice is increased. The secretion of the duodenum causes
a greater increase in the proteolytic power than that of the other
portions of the small intestine, while no such difference has been
made out in the case of the amylolytic and lipolytic functions. It is
probable that the enterokinase, which is secreted mainly in the upper
two -sevenths of the small intestine, and solely by the intestinal
epithelium, acts only on the trypsinogen, and that the amylopsin
and steapsin are aided in some other way. Enterokinase is only
found in the intestinal juice when pancreatic juice is present in the
gut. It is therefore secreted in response to the presence of tryp-
sinogen or of some other constituent of the pancreatic juice.
Delezenne has attempted to explain the interaction of enterokinase
and trypsinogen as an adaptive phenomenon of the same kind as the
formation of antitoxins and hsemolysins (p. 31). According to him,
enterokinase acts like a complement in haemolysis, while trypsinogen
plays the part of an intermediary body or amboceptor which enables
the enterokinase to attack the protein molecule. He asserts that
enterokinase, or a substance which produces a similar effect on tryp-
sinogen, is contained not only in the mucous membrane of the intestine,
but also in leucocytes, in fibrin (one of whose properties it is to pick
out ferments from liquids containing them), in lymph-glands, in snake
venom, and even in certain anaerobic bacteria. On this view trypsin
would not be a definite substance produced by the interaction of
enterokinase and trypsinogen, but only an expression for these two
bodies acting together. Strong evidence against this view, and in
favour of the independent existence of trypsin, haj been brought forward
by Bayliss and Starling, and it does not seem to merit further con-
sideration. According to Mellanby, enterokinase is really a proteolytic
ferment, and trypsinogen contains a protein moiety with which trypsin
is firmly combined. The conversion of trypsinogen into trypsin
depends on the digestion of this protein moiety, and the consequent
liberation of trypsin. Vernon has put forward the view that, while
enterokinase starts the activation of trypsinogen in the intestine,- and
can no doubt in time complete it, the .trypsin a.s it is formed aids in the
activation of more trypsinogen to trypsin, and so on by a process of
so-called auto-catalysis of the trypsinogen. This idea can be har-
monized with Mellanby's conception by assuming that the trypsin
formed from trypsinogen can itself digest the protein moiety of a further
portion of trypsinogen.
374 DIGESTION
According to Pawlow, the reason why the trypsin is not secreted
in the active form is that active trypsin readily destroys the amylo-
lytic and lipolytic ferments. In the intestine, where trypsin is
rendered active by enterokinase, these ferments are protected from
its attack by the proteins of the food and by the bile. Enterokinase
is itself immediately destroyed in the presence of free acid (centi-
normal hydrochloric acid).
Having now finished our review of the chemistry of the digestive
juices, our next task is to describe what is known as to their secre-
tion— the nature of the cells by which it is effected and their histo-
logical appearance in activity and repose, and the manner in which
it is called forth and controlled.
SECTION IV. — THE SECRETION OF THE DIGESTIVE JUICES —
MICROSCOPICAL CHANGES IN THE GLAND CELLS.
The digestive glands are formed originally from involutions of the
mucous membrane of the alimentary canal, the salivary glands from
the ectoderm, the others from the endoderm (Chap. XIX.). Some are
simple unbranched tubes, in which there is either no distinction into
body and duct, as in Lieberkuhn's crypts in the intestines, or in which
one or more of the tubes open into a duct, as in the glands of the f undus
of the stomach. Some are branched tubes, several of which may end
in a common duct ; such are the glands of the pyloric end of the stomach
and the Brunner's glands in the duodenum. In others the main duct
ramifies into a more or less complex system of small channels, into each
of the ultimate branches of which one or more (usually several) of the
secreting tubules or alveoli open. The salivary glands and the pancreas
belong to this class of compound tubular or racemose glands, and so
does the liver of such animals as the frog. But in the latter organ the
typical arrangement is obscured in the higher vertebrates by the pre-
dominance of the portal bloodvessels over the system of bile-channels
as a groundwork for the grouping of the cells.
In every secreting gland there is a vascular plexus outside the cells
of the gland-tubes, and a system of collecting channels on their inner
surface ; and in a certain sense the cells of every gland are arranged
with reference to the bloodvessels on the one hand, and the ducts on
the other. But in the ordinary racemose gland the blood-supply is
mainly required to feed the secretion ; the cells of the alveoli have either
no other function than to secrete, or if they have other fxmctions, they
are* not such as to entail a great disproportion between the size of the
cells and the lumen of the channels into which they pour their products.
For both reasons the relation of the grouping of the cells to the duct-
system is very obvious, to the blood-system very obscure. In the liver,
the conditions arc precisely reversed. We cannot suppose that the
manufacture of a quantity of bile less in volume than the secretion of
the salivary glands, though doubtless containing far more solids,
requires an immense organ like the liver, and a tide of blood like that
which passes through the portal vein. And, as we shall see, the liver
has other functions, some of them certainly of at least equal importance
with the secretion of bile, and one of them evidently requiring from
its very nature a bulky organ. Accordingly, both the richness of the
blood-supply and the size of the secreting cells are out of proportion to
THE SECRETION OF THE DIGESTIVE JUICES 375
the calibre of the ultimate channels that carry the secretion away.
The so-called bile-capillaries, which represent the lumen of the secreting
tubules, are mere grooves in the surface of adjoining cells; and the
architectural lines on which the liver lobule is built are: (i) the inter-
lobular veins which carry blood to it; (2) the rich capillary network
which separates its cells and feeds them; and (3) the central intra-
lobular vein which drains it. Thus a network of cells lying in the
meshes of a network of blood-capillaries takes the place of a regular
dendritic arrangement of ducts and tubules; and in accordance with
this the bile-capillaries, instead of opening separately into the ducts,
form a plexus with each other within the hepatic lobule (see also foot-
note, p. 14).
The ducts and secreting tubules of all glands are lined by cells of
columnar epithelial type, but the type is most closely preserved in the
ducts. In none of the digestive glands is there more than a single
complete layer of secreting cells. But the alveoli of the mucous
salivary glands show here aiul there a crescent-shaped group of small
deeply-staining cells (crescents of Gianuzzi) outside the columnar layer
(Fig. 158, A", B"), and between it and the basement membrane, while
the gland-tubes of the f undus of the stomach have in the same situation
a discontinuous layer of largo ovoid cells, termed parietal from their
position, oxyntic (or acid -secreting) from their supposed function
(Figs. 155-157). Access to the lumen of the glands is provided for
these deeply-placed parietal cells and for the cells of the crescents by
fine branching channels which enter and surround the cells. The
serous salivary glands, the pyloric glands of the stomach, and the
Lieberkiihn's crypts, have but a single layer of epithelium; and since
there is no hepatic cell which is not in contact with at least one bile
capillary, the liver may be regarded as having no more. The same is
true of the pancreatic alveoli, except that in the centre of many of the
acini a few spindle-shaped cells (centro-acinar cells), apparently con-
tinued from the lining of the smallest ducts, may be seen. Remarkable
histological changes, evidently connected with changes in functional
activity, have been noticed in most of the digestive glands. In dis-
cussing these, it will be best to omit for the present any detailed reference
to the liver, since, although there are histological marks of secretive
activity in this gland as well as in others, and of the same general
character, they are accompanied, and to some extent overlaid, by the
microscopic evidences of other functions (p. 534). The serous salivary
glands and the pancreas can be taken together; so can the glands of the
various regions of the stomach; the mucous salivary glands must
be considered separately.
Changes in the Pancreas and Parotid during Secretion.— The cells
of the alveoli of the pancreas or parotid during rest, as can be seen
by examining thin lobules of the former between the folds of the
mesentery in the living rabbit, or fresh teased preparations of the
latter, are filled with fine granules to such an extent as to obscure
the nucleus. In the parotid the whole cell is granular, in the
pancreas there is still a narrow clear zone at the outer edge of the
cell which contains few granules or none; in both, the divisions
between the cells are very indistinct, and the lumen of the alveolus
cannot be made out. During activity the granules seem to be
carried from the outer portion of the cell towards the lumen, and
376
there discharged. The clear outer zone of the pancreatic cell grows
broader and broader at the expense of the inner granular zone, until
at last the granular zone may in its turn be reduced to a narrow
contour line around the lumen (Fig. 153). In the uniformly clouded
parotid cell a similar change takes place; a transparent outer zone
arises; and, after prolonged
secretion, only a thin edging
of granules may remain at
the inner portion of the cell
(Fig. 154). In both glands
the outlines of the cells be-
come more clearly indicated,
and a distinct lumen can
now be recognized. The
cells are smaller than they
A B are during rest.
A , alveolus of rabbit's pancreas,
(resting) ; B, ' discharged '
Fig. 153--
' loaded
(active), observed in the living animal
(Kiihne and Lea).
The disappearance of
granules from without in-
wards during activity sug-
gests that these are manu-
factured products eliminated in the secretion, and they are generally
spoken of as zymogen granules.
Bensley, who has made a careful study of the pancreas in the
guinea-pig, has been able to distinguish, even in fresh preparations
examined in the animal's own serum, but better after staining with
such a dye as neutral red, another kind of granules, which he regards
Fig. 154. — Alveoli of Parotid Gland: A, at Rest; B, after a Short Period of Activity;
C, after a Prolonged Period of Activity (Fresh Preparations) (Langley). In A
and B the nuclei are obscured by the granules of zymogen.
as zymogen granules in the course of formation, and therefore
designates prozymogen granules. The resting acini show a clear
basal zone which is unstained, and a zone next the lumen containing
coarse zymogen granules which are faintly stained. In the active
gland — e.g.. after a meal or after the injection of secretin (p. 407) —
prozymogen granules which stain much more intensely than the
zymogen granules with neutral red make their appearance between
the zymogen granules, now much reduced in number and size, and
THE SECRETION OF THE DIGESTIVE JUICES
377
the clear outer zone. After prolonged secretion the zymogen granules
may be entirely absent from the cells, and only a narrow rim of
prozymogen granules can be seen around the lumen.
In one respect the pancreas differs remarkably from the salivary
glands — namely, in the presence of the islets of Langerhans —
characteristic groups of small
polygonal cells, richly sup-
plied with bloodvessels, but
not arranged in the form of
alveoli. Some observers state
that they are remarkably in-
creased in size, and even in
number when the pancreas is
caused to secrete actively by
repeated injections of secretin,
and also in starvation. But
it has been shown that this
conclusion was based upon
faulty methods of counting
the islets, and even of identi-
fying the islet cells. There
appears to be no foundation
for the view that they are
derived from the ordinary
secreting cells, and that they
can, in turn, give rise to new
alveoli by a process of pro-
liferation. It is far more
probable that they are inde-
pendent structures, with a
different function from the
pancreatic alveoli (p. 6^,8).
Changes in the Glands of
the Stomach during Secre-
tion.— The mucous membrane
of the stomach is covered
with a single layer of colum-
nar epithelium, largely con- Fig. 156.— A Fundus Gland prepared by
sisting of mucigenoUS goblet- GolSi>s Method, showing the Moda of Com-
,, J T ° j A ,° . , munication of the Parietal Cells with the
IS Studded Wltn Gland-Lumen (Schafer, after E. Muller).
minutt pits, into which open
the ducts of the peptic and pyloric glands, the ducts being lined
with cells just like those of the general gastric surface. Three
varieties of gastric glands have been distinguished: (i) The
glands of the cardia. In man these occupy a small portion of
the mucous membrane at the cardiac end, near the orifice of
Fig. 155. Fig. 156.
Fig. 155. — A Fundus Gland of Simple Form
from the Bat's Stomach (Osmic Acid Pre-
paration) (Langley). c, Columnar epithe-
lium of the surface; n, neck of the gland
with chief or central and parietal cells;
/, base, occupied only by chief cells, which
show the granules accumulated towards
the lumen of the gland.
378 DIGESTION
the oesophagus. Some of the glands are single tubules, but
others have two or more tubules opening into a common duct.
Both are lined by a single layer of short columnar epithelium,
which contains granules. (2) The glands of the pyloric canal
or antrum. These consist of short, branched tubules, which open
by twos and threes into long ducts. (3) The glands of the
fundus or oxyntic glands, occupying the intermediate and greater
portion of the organ. The gland tubules are long and seldom
branched, and the ducts, into each of which open from one to three
tubules, are relatively short. The secreting parts of both kinds of
glands are lined by short columnar granular cells; and in the pyloric
tubules no others are present. But, as we have said, in the glands
of the fundus there are besides large ovoid cells scattered at intervals
like beads between the basement membrane and the lining or chief
cells. The cells of the pyloric glands have a general resemblance to
the chief cells of the fundus glands, but they are not quite the same.
For example, the granules are less distinct in the pyloric glands. In
the human stomach it is only quite near the pylorus that the parietal
cells disappear altogether. The parietal cells also contain granules,
but they are smaller and less numerous than those of the chief cells,
so that the deeper portions of the fundus glands are much darker in
appearance than the more superficial portions, since the oxyntic or
parietal cells are more numerous in the neighbourhood of the ducts
(Bensley).
The histological changes connected with gastric secretion do not
differ essentially from those described in the pancreas and the
parotid, but there is much greater difficulty in making observations
on the living, or at least but slightly altered, cells. For the mammal
the best method is to use animals with a permanent gastric fistula,
and to remove from time to time small portions of the mucous
membrane for examination in the fresh condition. During digestion
the granules disappear from the outer part of the chief cells of the
fundus glands, leaving a clear zone, the lumen being bordered by a
granular layer. Or, more rarely, there may be a uniform decrease
in the number of granules throughout the cell. The total volume
of the cell is less than in the fasting condition. The parietal cells,
which are small in the fasting animal, swell up, so as to bulge out the
membrana propria. They reach their maximum size (in the dog)
very late in digestion (the thirteenth to the fifteenth hour). No
such definite changes in their contents as those observed in the other
cells have been made out. The granules in the ovoid cells during
and after activity seem to be as large and as numerous as in the
resting cell, or even larger. After sham feeding in dogs the histo-
logical changes in the gastric glands are very slight, even when con-
siderable amounts of gastric juice have been secreted (Noll and
Sokoloff).
THE SECRETION OF THE DIGESTIVE JUICES
379
The chief cells of the oxyntic, and the similar if not identical cells
of the pyloric glands, are believed to manufacture the pepsin-form-
ing substance. The ovoid cells of the former are supposed to secrete
the hydrochloric acid. The evidence on which this belief is based
is as follows:
The glands of the antrum pylori in the dog, in which in most
situations no ovoid cells are to be seen, secrete pepsin, but no acid.
The pyloric end of the stomach or a portion of it has been isolated,
Fig- I57- — The Gastric Glands (Ebstein). On the left, oxyntic; right, pyloric.
the continuity of the alimentary canal restored by sutures, and the
secretion of the pyloric pocket collected. It was found to be alka-
line, and contained pepsin. The glands of the frog's oesophagus,
which contain only chief cells, secrete pepsin, but no acid. It seems
fair to conclude that the chief cells of the fundus glands in the
mammal secrete none of the free hydrochloric acid, but certainly
some of pepsin. But it does not follow that all the pepsin is formed
by these cells, although it would seem that all the hydrochloric acid
380 DIGESTION
must be secreted by the only other glandular elements present, the
parietal or ' border ' cells. And, indeed, the glands in the fundus
of the frog's stomach, which are composed only of ovoid cells, whilst
secreting much acid, also form some pepsin, although far less than
the cesophageal glands. During winter sleep (in the marmot) the
production of hydrochloric acid in the parietal cells stops altogether,
while the chief cells continue to accumulate granules of pepsinogen.
That some pepsin is secreted by the pyloric end of the stomach
is not difficult to prove. The secretion collected from the isolated
pyloric portion is, indeed, like the secretion of the Brunner's glands
in the duodenum, quite unable to digest protein until dilute hydro-
chloric acid is added. But this is because in both cases the juice as
it flows from the glands is slightly alkaline, and, as we have already
seen, pepsin only acts in the presence of an acid. The milk-curdling
action of these two juices also unfolds itself only when the secretions
are first acidulated, and later on again neutralized ; in other words,
the ferments must be activated by the addition of an acid. In normal
digestion the pepsin of the (in itself) alkaline secretion of the pyloric
end of the stomach becomes a constituent of the acid gastric juice;
and it may perhaps be considered a morphological accident, so to
speak, that the oxyntic cells of the fundus should mingle their acid
products with the (presumedly) alkaline secretion of the chief cells
in the lumen of each gland-tube, instead of being massed as a
separate organ with a special duct.
We are not without other examples of digestive juices fitted or
destined to act in a medium with an opposite reaction to their own.
The ' saliva ' of the cephalopod Octopus macropus, strongly acid
though it is, contains a proteolytic ferment which in vitro acts, like
trypsin, better in an alkaline than in an acid solution. And trypsin,
whose precursor is a constituent of the alkaline pancreatic juice, while
the enterokinase which activates it is a constituent of the alkaline
succus entericus, performs a part at least of its work in an acid
medium.
Attempts made to demonstrate an acid reaction in the border cells
have hitherto failed. Harvey and Bensley on the basis of experiments
with dyes (cyanimin and neutral red), which give different colours
according to whether the reaction is acid, alkaline, or neutral, have
concluded that free acid exists only on the internal surface of the
stomach, or at most also in the necks of the glands. The parietal cells
they find alkaline. They suggest that these cells form in some way,
of course ultimately from the chlorides of the blood, a chloride of an
organic base which does not decompose so as to yield free hydrochloric
acid until it reaches the mouth of the gland. The nature of this decom-
position, if it occurs, is unknown. It may be mentioned, although only
as a matter of historical interest, that some observers have denied that
the acid is secreted in the depths of any cell from the chlorides of the
blood, and have asserted that it is formed at the surface of contact of
the stomach-wall with the gastric contents from the sodium chloride of
the food by an exchange of sodium ions (p. 428) for hydrogen ions from
THE SECRETION OF THE DIGESTIVE JUICES 381
the blood or lymph. It was pointed out in favour of this view that
when, instead of sodium chloride, sodium bromide is given in the food,
the hydrochloric acid in the stomach is to a large extent replaced by
hydrobromic acid. And it was argued that this cannot be due to the
decomposition of the bromide by hydrochloric acid, since it occurs in
animals deprived for a considerable time of salts, and in ' salt-hunger '
the stomach contains no acid (Koeppe). It may be, however, that
even in ' salt -hunger ' the presence of sodium bromide in the stomach
stimulates the secretion of hydrochloric acid, which then decomposes
the bromide, with the formation of hydrobromic acid. The sodium
chloride formed in the double decomposition might be re-absorbed,
and the stock of chlorides in the blood remain undiminished. It is in
any case a decisive objection to this now defunct theory that a copious
secretion of gastric juice, containing hydrochloric acid in abundance,
can be obtained, without the introduction of any food into the stomach,
either by the process of sham feeding (p. 401) or by psychical simulation
of the gastric glands when food is shown to an animal.
Changes in Mucous Glands during Secretion. — In the mucous salivary
and other mucous glands similar, but apparently more complex, changes
occur. During rest the cells which line the lumen may be seen in fresh,
teased preparations to be filled with granules or ' spherules.' After
active secretion there is a great diminution in the number of the
granules. Those that remain are chiefly collected around the lumen,
although some may also be seen in the peripheral portion of the cell;
and there is no very distinct differentiation into two zones. That a
discharge of material takes place from these cells is shown by their
smaller size in the active gland. That the material thus discharged is
not protoplasmic is indicated by the behaviour of the cells to proto-
plasmic stains such as carmine. The resting cells around the lumen
stain but feebly, in contrast to the deep stain of the demilunes, while
the discharged cells take on the carmine stain much more readily.
Further, when a resting gland is treated with various reagents (water,
dilute acids, or alkalies), the granules swell up into a transparent sub-
stance identical with mucin, which fills the meshes of a fine protoplasmic
network.
In ordinary alcohol-carmine preparations only the network and
nucleus are stained ; the nucleus, small and shrivelled, is situated close
to the outer border of the cell. When a discharged gland is treated in
the same way there is proportionally more ' protoplasm ' (or ' bioplasm ')
and less of the clear material, what remains of the latter being chiefly
in the inner portion of the cell, while the nucleus is now large and
spherical, and not so near the basement membrane (Fig. 158).
Everything, therefore, points to the granules in what we may now
call the mucin-forming cells as being in some way or other precursors
of the fully-formed mucin ; manufactured during ' rest ' by the proto-
plasm and partly at its expense, moved towards the lumen in
activity, discharged as mucin in the secretion. It has been asserted
that not only is the protoplasm lessened in the loaded cell and re-
newed after activity, but that many of the mucigenous cells may be
altogether broken down and discharged, their place being supplied
by proliferation of the small cells of the demilunes. This conclusion,
however, is not supported by sufficient evidence. The cells of the
crescents contain fine granules, but none which can be changed into
382 DIGESTION
nmcin. They are of serous and not of mucous type. But the fact
on which we would specially insist is that the granules of the resting
mucigenous cell may be looked upon as a mother-substance from
which the mucin of the secretion is derived ; they are not actual, but
potential, mucin.
So in the pancreas, the serous or albuminous salivary glands, and
the glands of the stomach, there is every reason to believe that the
granules which appear in the intervals of rest, and are moved
towards the lumen and discharged during activity, are the pre-
cursors, the mother-substances, of important constituents of the
secretion. These granules are sharply marked off from the proto-
plasm in which they lie and by which they are built up. By every
mark, by their reaction to stains, for instance, they are non-living
substance, formed in the bosom of the living cell from the raw
material which it culls from the blood, or, what is more likely,
formed from its own protoplasm, then shed out in granular form and
Fig. 158. — Mucous Cells (from Submaxillary of Dog) in Rest and Activity (Langley).
A, B, fresh; A', B', after treatment with dilute acetic acid; A", B*, alveoli hard-
ened in alcohol and stained with carmine. A, A', and A* represent the loaded;
B, B', and B", the discharged condition.
secluded from further change. The granules in the ferment-forming
glands are not in general composed of the actual ferments, and,
indeed, in several instances it has been shown that the actual fer-
ments are not present in the secreting cells at all.
We have already seen that the pancreas and even the fresh pan-
creatic juice are devoid of active trypsin. Similarly, a glycerin
extract of a fresh gastric mucous membrane is inert as regards
proteins, or nearly so. But if the mucous membrane has been pre-
viously treated with dilute hydrochloric acid, the glycerin extract
is active, as is an extract made with acidulated glycerin. Here we
must assume the existence in the gastric glands of a mother-sub-
stance, pepsinogen, from which pepsin is formed. The rennin of the
gastric juice, which is formed in the chief cells, also has a precursor,
which, if the ferment is identical with pepsin (p. 353), must be
pepsinogen. The proteolytic power of an extract of the pancreas,
THE SECRETION OF THE DIGESTIVE JUICES 3.83
when the trypsinogen has been activated into trypsin, or of the
gastric mucous membrane, when the pepsinogen has been changed
into pepsin, seems to be, roughly speaking, in proportion to the
quantity of granules present in the cells. Therefore it is concluded
that the granules represent mother-substances of the ferments or
zymogens. Some observers believe they have obtained evidence of
stages in the elaboration of the ferments still further back than the
mother-substances, grandmother-substances so to speak, or pro-
zymogens. Bensley, e.g., concludes that the nuclei of the chief cells
in the fundus glands of the stomach take part in the formation of a
prozymogen, the precursor of the zymogen or pepsinogen, as pepsino-
gen is the precursor of the enzyme pepsin.
A glycerin or watery extract of the salivary glands always con-
tains active amylolytic ferment, if the natural secretion is active.
So that if ptyalin is preceded by a zymogen in the cells, it must be
very easily changed into the actual ferment.
But we should greatly deceive ourselves if we supposed that granules
of this nature in gland-cells are necessarily related to the production of
ferments. The mucigenous granules have no such significance. Most
digestive secretions contain protein constituents, with which the
granules may have to do as well as with ferments. And bile, a secretion
which contains no mucin, no proteins, and either no ferments or mere
traces, as essential and original constituents, is formed in cells with
granules so disposed and so affected by the activity of the gland as to
suggest some relation between them and the process of secretion. In
the liver-cells of the frog, in addition to glycogen, and oil-globules small
granules may be seen, especially near the lumen of the gland tubules ;
they diminish in number during digestion, when the secretion of bile is
active and increase when food is withheld and secretion slow. And
in fasting dogs the secreting cells of Brunner's glands, the pyloric glands
and the pancreas, as well as the lining epithelium of the bile-ducts,
have been found to contain many fatty granules. Possibly some of
these represent the fat which is known to be excreted into the alimentary
canal (pp. 443, 444).
The Nature of the Process by which the Digestive Secretions are
Formed. — We have spoken more than once of the gland-cells as
manufacturing their secretions. It is an idea that rises naturally
in the mind as we follow with the microscope the traces of their
functional activity. And when we compare the composition of the
digestive juices with that of the blood-plasma and lymph, the
suggestion that the glands which produce them are not merely
passive niters, but living laboratories, acquires additional strength.
It is evident that everything in the secretion must, in some form
or other, exist in the blood which comes to the gland, and in the
lymph which bathes its cells. No glandular cell, if we except the
leucocytes, which in some respects are to be considered as unicellular
glands, dips directly into the blood ; everything a gland-cell receives
must pass through the walls of the bloodvessels. (But see footnote
384 DIGESTION
on p. 14). So that anything which we find in the section and do
not find in the blood must have been elaborated by the gland
epithelium (or by the capillary endothelium) from raw material
brought to it by the blood.
Take, for example, the saliva or gastric juice. These liquids both
contain certain things that also exist in the blood, but in addition
they contain certain things specific to themselves: mucin in saliva,
hydrochloric acid in gastric juice, ferments in both. It is true that
a trace of 'pepsin and a trace of a diastatic ferment may be dis-
covered in blood; but there is no reason whatever to believe that
this is the source of the pepsin of the gastric juice, or the ptyalin
of the salivary glands, except, perhaps, in animals like the cat,
whose saliva contains a diastase in still smaller concentration than
the serum (Carlson). On the contrary, it is possible that the fer-
ments of the blood may be in part absorbed from the digestive
glands, the rest being formed by the leucocytes and liberated when
they break down.
Formation of Bile. — The liver affords an even better example of
this ' manufacturing ' activity of gland-cells, and many facts may
be brought forward to prove that the characteristic constituents
of the bile, the bile-pigments and bile-acids, are formed in the liver,
and not merely separated from the blood. Bile-pigment has indeed
been recognized in the normal serum of the horse, and bile-acids in
the chyle of the dog, but only in such minute traces as are easily
accounted for by absorption from the intestine. Frogs live for some
time after excision of the liver, but no bile-acids are found in the
blood or tissues. But if the bile-duct be ligatured, bile-acids and
pigments accumulate in the body, being absorbed by the lymphatics
of the liver (Ludwig and Fleischl). If the thoracic duct and the
bile-duct are both ligatured in the dog, no bile-acids or pigments
appear in the blood or tissues. Wertheimer and Lepage state that
bile or bilirubin injected into a bile-duct appears sooner in the
urine than in the lymph of the thoracic duct, and therefore conclude
that the bloodvessels are the most important channel of absorption.
This conclusion, however, cannot be accepted until it is shown that
in these experiments the injection did not cause rupture of some
of the hepatic capillaries and direct entrance of the bile-pigment
into the blood. It is not improbable that the pressure attained by
the bile in the bile-capillaries is a factor in determining the path
by which it is absorbed, and that when the pressure rises beyond
a certain limit it may pass both into the bloodvessels and into the
lymphatics. In mammals life cannot be maintained for any length
of time after ligature of the portal vein, since this throws the whole
intestinal tract out of gear. But after an artificial communication
has been made between the portal and the left renal vein or the
inferior cava, the portal may be tied and the animal live for months
THE SECRETION OF THE DIGESTIVE JUICES 385
(Eck). The liver can- now be completely removed, but death
follows in a few hours. A good method of establishing an- Eck's
fistula i's to make a longitudinal incision in the inferior vena cava
and the portal or superior mesenteric vein, and to suture the edges
of the two openings together with a very fine sewing-needle and
thread (Carrel and Guthrie). In birds there exists a communicating
branch between the portal vein and a vein (the renal-portal) which
passes from the posterior portion of the body to the kidney, and
there breaks up into capillaries ; and not only may the portaL be
tied, but the liver may be completely destroyed without immedi-
ately killing the animal. In the hours of life that still remain to it
no accumulation of biliary substances (acids or pigments) takes*
place in the blood or tissues. A further indication that bile-pig-
ment is produced in the liver is the fact that the liver contains
iron in relative abundance in its cells (p. 21), and eliminates small
quantities of iron in its secretion. Now, bile-pigment, which con-
tains no iron, is certainly formed from blood-pigment, which is rich
in iron. For haematin, when injected under the skin, has been found
to appear almost quantitatively in the form of bile-pigment in the
bile, and haematoidin (Fig. 159), a crystalline
derivative of haemoglobin found in old ex-
travasations of blood, especially in the brain
and in the corpus luteum, is identical with
bilirubin. The fact that one of the derivatives
of haematin, haematoporphyrin (C33H38N4O6),
contains no iron, and is probably nearly
related to bilirubin (C32H36N4O6), suggests
that haematoporphyrin may be an inter- pig I59Z^raatoidin.
mediate step in the formation of bile-pigment
from blood- pigment. In any case, the seat of formation of bile-
pigment might be expected to be an organ peculiarly rich in iron.
The existence of haematoidin, however, shows that bile-pigment
may, under certain conditions, be formed outside of the hepatic
cells. The occurrence of biliverdin in the placenta of the bitch
points in the same direction. But the pathological evidence in
favour of the pre-formation of the biliary constituents tends rather
to shrink than to increase. For many cases of what used to be
considered ' idiopathic ' or ' haematogenic ' jaundice, i.e., an accumu-
lation of bile-pigments and bile-acids in the tissues, due to defective
elimination by the liver, are now known to be caused by obstruction
of the bile-ducts and consequent re-absorption of bile (' obstructive '
or ' hepatogenic ' jaundice).
But if substances such as the ferments, mucin, hydrochloric acid,
the bile-salts and bile-pigments, are undoubtedly manufactured in the
gland-cells, it is different with the water and inorganic salts which
form so large a part of every secretion. No tissue lacks them ; no
25
386
DIGESTION
physiological process goes on without them ; they are not high and
special products. As we breathe nitrogen which we do not need
because it is mixed with the oxygen we require, the secreting cell
passes through its substance water and salts as a sort of by-play or
adjunct to its specific work. But this is not the whole truth. The
gland-cell is not a mere filter through which water and salts pass in
the same proportions in which they exist in the liquids that the
cell draws them from. When, e.g., the salivary glands secrete
against the resistance of an abnormally high pressure in the ducts,
the percentage of salts in the saliva increases. The secretions of
different glands differ in the nature, and especially in the relative
proportions, of their inorganic constituents. They differ also in
their osmotic pressure and electrical conductivity, which depend
so largely upon those constituents, notwithstanding the fact that
the osmotic pressure and conductivity of the blood-serum (p. 26)
vary only within narrow limits. Even the secretion of one and the
same gland is by no means constant in this respect, as we shall
have to note more especially when we come to deal with the in-
fluence of the nervous system on secretion (p. 395). The following
tables illustrate this point :
Dog.
Blood-Serum.*
Filtrate of Gastric Contents.
At
KJ(5°C.)xio«.
A
KI(5°C.)xio«.
I.
II.
III.
0-643°
0-628°
O'6O2°
92-0
87-6
87-7
0-5850
0-585°
0-642°
312-5
179-4
351-7
Vomit of man with complete intes-
tinal obstruction -
0-433°
84-7
Pancreatic Juice of Dog (Pincussohn) .
Diet.
A
Milk
o-57°— <
j-630
Cauliflower
0-58°— <
3-63°
Horseflesh
0-62°— <
>-63°
* The blood and gastric contents were obtained from the animals twenty-
four hours after the last meal.
f The depression of the freezing-point below that of distilled water.
J See footnote on p. 27. The number in brackets is the temperature at
which the measurement was made.
THE SECRETION OF THE DIGESTIVE JUICES
387
Gastric Juice from Miniature Stomach in a Dog in Different
Experiments (Bickel) .
Milk Diet.
Meat Diet.
A
K(25oC.)Xio*.
A
K(2s°C.)xio«.
0-52°
195*9
0-60°
310-3
0-65°
402'6
O-yi0
473-5
0-64°
436-5
1-21°
483*3
0-69°
404-2
o-79°
5i4'i
0-81°
436-5
0-70°
SH'i
A of Blood and Saliva Compared (Jappelli}.
A of Blood.
A of Submaxillary Saliva of Dog.
0-570°
0-610°
0-600°
0-590°
0-580°
0-605°
0-650°
0-610°
0-410°
0-350°
0-430°
0-410°
0-450°
0-425°
0-380°
0-475°
A of Human Fistula Bile.
A of Human Bladder Bile.
0-56°
0-547°
0-615°
0-60°
0-545°
0-65°
0-865«
0-78°
0-92°
A of Dog's Submaxillary Saliva.
Chorda stimulated :
Left submaxillary - 0-293*
Both glands - 0-408°
Spontaneous secretion :
Right submaxillary - - - -0-195°
A of dog's serum - - 0-590°
The protein substances, such as serum-albumin and globulin,
common to blood and to some of the digestive secretions, take a
middle place between the constituents that are undoubtedly manu-
338
DIGESTION
factured in the cell and those which seem by a less special and
laborious, though a selective, process to be passed through it from
the blood. Their practical absence from bile, and, as we shall see,
from urine, their relative abundance in pancreatic and scantiness
in gastric juice, point to a closer dependence upon the special
activity of the gland-cell than we can suppose necessary in the case
of the salts.
Although it is in the cells of the digestive glands that the power of
forming ferments is most conspicuous, it is by no means confined to
them. It seems to be a primitive, a native power of protoplasm.
Lowly animals, like the amoeba, lowly plants, like bacteria, form ferments
within the single cell which serves for all the purposes of their life.
TTie ferment-secreting gland-cells of higher forms are perhaps only lop-
sided amoebae, not so much endowed with new properties as dispro-
portionately developed in one direction. The contractility has been
lost or lessened, the digestive power has been retained or increased;
just as in muscle the power of contraction has been developed, and
that of digestion has fallen behind. The muscle-cell and the cartilage-
cell are parasites, if we look to the function of digestion alone. They
live on food already more or less prepared by the labours of other cells;
and it is a universal law that in the measure in which a power becomes
useless it disappears. But the presence of pepsin in the white blood-
corpuscles, the parasites as well as the scavengers of the blood, and of
amylolytic, proteolytic and lipolytic ferments in many tissues, should
warn us not to conclude that the power of forming ferments belongs
exclusively to any class of cells. There is good and growing evidence
that food-substances absorbed from the blood are further decomposed
and, in turn, elaborated by ferment action within the tissues them-
selves ; while many facts show that the power of contraction is widely
diffused among structures whose special function is very different,
and a few point to its possession in some degree even by glandular
epithelium. On the other hand, it must be remembered that none of
the digestive glands absorb food directly from the alimentary canal to
be then digested within their own cell-substance; the ferments which
they form do their work outside of them ; their cells feed also upon the
blood.
Why are the Tissues of Digestion not affected by the Digestive
Ferments ? — This is the place to mention a point which has been
very much debated. Why is it that the stomach or the small intes-
tine does not digest itself ? This is really a part of a wider question :
Why is it that living tissues resist all kinds of influences, which attack
dead tissues with success ? And we have to inquire whether the
immunity of the alimentary canal to the digestive juices is an
example of a general resistance of all living tissues to destructive
agencies, or a specific resistance of certain tissues to certain in-
fluences.
That all living tissues cannot withstand the action of the gastric
juice has been shown by putting the leg of a living frog inside the
stomach of a dog; the leg is gradually eaten away (Bernard).
It is true that it has first been killed and then digested, but the
question is, why the stomach-wall is not first killed and then
THE SECRETION OF THE DIGESTIVE JUICES s8g
digested ? When the wall has been injured by caustics or by an
embolus, the gastric juice acts on it. But the living epithelium
that covers it is able to resist the action of the acid and pepsin,
which destroys the tissues of the frog's leg. The explanation is not
to be found in the alkalinity of the blood, for the frog's blood is also
alkaline, and the cells that line the intestine are preserved from the
pancreatic juice, which is intensely active in an alkaline medium,
while the living frog's leg is not harmed by a weakly alkaline pan-
creatic extract, which does not digest the epithelium because it
cannot kill it. A certain amount of protection may be afforded to
the walls of the stomach by the thin layer of mucus which covers the
whole cavity, for mucin is not affected by peptic digestion. And
a mucous secretion seems in some other cases to act as a protective
covering to the walls of hollow viscera, whose contents are such as
would certainly be harmful to more delicate membranes, e.g., in
the urinary bladder, large intestine, and gall-bladder. Still, how-
ever important such a mechanical protection may be, it does not
explain the whole matter, and it is necessary to suppose that the
gastric epithelium has some special power of resisting the gastric
juice, either by turning any of the ferment which may invade it
into an inert substance and neutralizing any intrusive acid, or by
opposing their entrance as the epithelium of the bladder opposes the
absorption of urea. There is reason to believe that, as a matter of
fact, free hydrochloric acid cannot penetrate the living cells, and
it is to be noted that both active pepsin and free acid must be
present at the same point within the cells before digestion of them
can take place. In the gland-cells of the pancreas the protoplasm
is, no doubt, shielded from digestion by the existence of the ferment
in an inert form as zymogen ; and it is possible that this is one of the
reasons for the existence of the mother-substance. But no such
explanation is, of course, available for the intestinal epithelium.
Trypsin when injected below the skin causes the tissue to break
down and ulcerate. And while an active solution of trypsin can
be allowed to remain a long time in an isolated loop of small intes-
tine without producing any ill effect, damage is soon caused not
only to the intestinal wall, but also to the liver, when the mucous
membrane of the loop has been injured before the introduction of
the trypsin. We must suppose, then, that the normal mucous
membrane of the intestine prevents the absorption of trypsin, or,
if it absorbs any of it, renders it harmless. On the other hand, .the
intestinal mucosa is injured by the natural gastric juice when intro-
duced directly into it unless the animal takes food simultaneously
or a little earlier. But for reasons already given (p. 370) injury to
the intestine cannot be produced in this way in normal digestion.
It is impossible to escape the conclusion that each membrane becomes
accustomed, and, so to speak, ' immune,' to the secretion normally
39°
DIGESTION
in contact with it, although not necessarily to other secretions.
It is easy to multiply illustrations of this principle.
The mucosa of the dog's urinary bladder is digested by the
natural activated pancreatic juice of the dog, and still more readily
by the natural gastric juice. Yet few tissues but the lining of the
urinary tract or of the large intestine could bear the constant contact
of urine or faeces. When urine is extravasated under the skin, or
the contents of the alimentary canal burst into the peritoneal
cavity, they come into contact with tissues which, although alive,
are much less fitted to resist them than the surfaces by which they
are normally enclosed; and the consequences, which are not wholly
due to infection, are often disastrous. Leucocytes thrive in
the blood, but perish in urine. Blood does not harm the endo-
thelial cells of the vessels, but kills a muscle whose cross-section
is dipped into it. The defensive or, in some cases, offensive
liquids secreted by many animals are harmless to the tissues
which produce and enclose them. A caterpillar investigated
by Poulton secretes a liquid so rich in formic acid that the mere
contact of it would kill most cells. The so-called saliva of Octopus
macropus contains a substance fatal to the crabs and other animals
on which it preys. The blood of the viper contains an active
principle similar to that secreted by its poison-glands, but its tissues
are not affected by this substance, so deadly to other animals.
A step in the solution of our problem has been taken by Wein-
land. Starting with the idea that if special protective mechan-
isms against the digestive juices were anywhere to be found, it would
be in the intestinal parasites whose whole existence is passed among
them, he has made the important discovery that in these parasitic
worms specific antiferments exist — i.e., substances which inhibit the
action either of pepsin or of trypsin or of both. These substances can
be precipitated from the expressed juice of the worms by alcohol,
without completely losing their activity. Fibrin can be impreg-
nated with them, and it is then, just like the ' living tissue,' rendered
for a longer or shorter time unassailable by the proteolytic ferments.
These facts are full of suggestion for future work, although the sup-
posed proof that similar antiferments are contained in the cells of
the mucous membrane of the stomach and intestines of the higher
animals appears to have broken down. Substances can indeed be
obtained by Weinland's method from the gastric and intestinal
mucosa which, when added to a digestive mixture, strongly inhibit
the digestion of proteins. But there is no clear proof that these sub-
stances are specific antiferments. They are probably merely some
of the split products of protein (Langenskjold). There is, however,
some evidence of the existence of an antipepsin in many tissues
including the mucous membrane of the stomach. As already men-
tioned, it is known that an antitrypsin exists in the blood, with the
INFLUENCE OF NERVOUS SYSTEM ON DIGESTIVE GLANDS 391
same properties as the antitrypsin in the intestinal worms (Hamill).
This explains the resistance of blood-serum to the digestive action
of trypsin. In addition to this body, which hinders the action of
fully-formed trypsin, and has no effect upon enterokinase, the
serum of some animals contains an antikinase — i.e., a substance
which hinders the action, not of trypsin, but of enterokinase, pre-
venting it from activating the trypsinogen into trypsin.
SECTION V. — THE INFLUENCE OF THE NERVOUS SYSTEM
ON THE DIGESTIVE GLANDS.
The Influence of Nerves on the Salivary Glands. — All the salivary
glands have a double nerve-supply, from the medulla oblongata
through some of the cranial nerves, and from the spinal cord through
the cervical sympathetic (Fig. 160).
In the dog the chorda tympani branch of the facial nerve carries the
cranial supply of the sublingual and submaxillary glands. It joins the
lingual branch of the fifth nerve, runs in company with it for a little
way, and then, breaking off, after giving some fibres to the lingual,
passes, as the chorda tympani proper, along Wharton's duct to the
submaxillary gland. In the hilus of this gland most of its fibres break
up into fibrils around nerve-cells situated there, and lose their medulla
in doing so. A few fibres terminate in a similar manner before entering
the hilus, and a few deeper in the gland. The nervous path is continued
by the axis-cylinder processes (p. 851) of these nerve-cells, which,
passing in as non-medullated fibres, end in a plexus on the basement
membrane of the alveoli. From the plexus fibrils run in among the
gland-cells, but do not seem to penetrate them. The lingual, the
chorda tympani proper, and Wharton's duct form the sides of what is
called the chordo-lingual triangle. Within this triangle are situated
many ganglion cells, a special accumulation of which has received the
name of the submaxillary ganglion. This, however, should rather be
called the sublingual ganglion, since its cells, as well as the others in the
chordo-lingual triangle, are the cells of origin of axons which proceed
as non-medullated fibres to the sublingual gland. The sublingual gland
receives its cerebral fibres partly from branches given off from the
lingual in the chordo-lingual triangle after the chorda tympani proper
has separated from it, and ending around the nerve-cells within that
triangle, partly from the chorda itself in the terminal portion of its
course. These statements rest on anatomical and physiological evi-
dence. The latter we shall return to.
The cerebral fibres for the parotid (in the dog) pass from the tympanic
branch of the glosso-pharyngeal (Jacobson's nerve) through connecting
filaments to the small superficial petrosal branch of the facial, with
this nerve to the otic ganglion, and thence by the auriculo-temporal
branch of the fifth to the gland.
The sympathetic fibres for all the salivary glands appear to arise from
nerve-cells in the upper dorsal portion of the spinal cord. Issuing
from the cord in the anterior roots of the upper thoracic nerves (first to
fifth, but mainly second thoracic for the submaxillary), they enter the
sympathetic chain, in which they run up to the superior cervical
ganglion. Here they break up into terminal twigs, and thus come into
DIGESTION
VJ1
relation with ganglion cells, whose axons pass out as non-medullated
fibres, and, surrounding the external carotid, reach the salivary glands
along its branches. Langley has shown, by means of nicotine (p. 182),
that the sympathetic fibres for the submaxillary and sublingual, and,
indeed, for the head in general in the dog and cat, are connected with
nerve-cells in this ganglion, but not between it and their termination,
or between it and their origin from the spinal cord.
Stimulation of the
Cranial Fibres. — When
in a dog a cannula is
placed in Wharton's
duct, and the saliva
collected (p. 456), it is
found that stimulation
of the peripheral end
of the divided chorda
causes a brisk flow of
watery saliva, and at
the same time a dila-
tation of the vessels
of the gland, which we
have already described
in dealing with vaso-
motor nerves (p. 179).
Notwithstanding the
vaso - dilatation, the
volume of the gland
is in general dimin-
ished, owing to the
rapid passage of water
into the duct (Bunch).
The blood has been
shown to lose water in
making the circuit of
the submaxillary
gland during excita-
tion of the chorda,
but doubtless some
of the water of the
saliva comes directly
Fig. 160 — Nerves of the Salivary Glands. SM and SL,
submaxillary and sublingual glands; P, parotid;
V, fifth nerve; VII, facial; GP, glosso-pharyngeal;
L. lingual; CT, chorda tympani; CL, chordo-lingual ;
D, submaxillary (Wharton's) duct; C, ganglion cell
of so-called submaxillary ganglion in the chordo-
lingual triangle, connected with a nerve fibre going
to sublingual gland; C", ganglion cell in hilus of sub-
maxillary gland; SSP, small superficial petrosal
branch of the facial; OG, otic ganglion; IM, inferior
maxillary division of fifth nerve; AT, auriculo-
temporal branch of fifth; JN, Jacobson's nerve;
C', gangUon cells in superior cervical ganglion (SG)
connected with sympathetic fibres going to parotid,
submaxillary and sublingual glands. The figure is
schematic.
from the cells or from
the lymph. That the increased secretion is not due merely to the
greater blood- supply, and the consequent increase of capillary pres-
sure, is shown by the injection of atropine, after which stimulation
of the nerve, although it still causes dilatation of the vessels, is not
followed by a flow of saliva. This can be shown fully as well by
injecting a small quantity of yohimbin into the submaxillary artery.
Great dilatation of the vessels is produced, but no saliva is secreted;
INFLUENCE OF NERVOUS SYSTEM ON DIGESTIVE GLANDS 393
nor is the amount of oxygen consumed by the gland increased.
Mere increase of pressure could not in any case of itself account for
the secretion, since it has been found that the maximum pressure
in the salivary duct when the outflow of saliva from the duct is
prevented may, during stimulation of the chorda, much exceed the
arterial blood-pressure (Ludwig). In one experiment, for example,
the pressure in the carotid of a dog was 125 mm., in Wharton's
duct 195 mm. of mercury.
Even in the head of a decapitated animal a certain amount of
saliva may be caused to flow by stimulation of the chorda, but too
much may easily be made of this. And since the blood is the ultimate
source of the secretion, we could not expect a permanent or copious
flow in the absence of the circulation, even if the gland-cells could
continue to live. In fact, when the circulation is almost stopped by
strong stimulation of the sympathetic, the flow of saliva caused by
excitation of the chorda is at the same time greatly lessened or
arrested, even though the sympathetic itself possesses secretory
fibres. So that, while there is no doubt that the chorda tympani
contains fibres whose function is to increase the activity of the
gland-cells, its vaso-dilator action is, under normal conditions,
closely connected with, and, indeed, auxiliary to, its secretory action,
although the dilatation of the vessels does not directly produce the
secretion. This is only a particular case of a physiological law of
wide application, that an organ in action in general receives more
blood than the same organ in repose, or, in other words, that the
tissues are fed according to their needs. The contracting muscle, the
secreting gland, is flushed with blood, not because an increased blood-
flow can of itself cause contraction or secretion, but because these
high efforts require for their continuance a rich supply of what blood
brings to an organ, and a ready removal of what it takes away.
Evidence exists that in the salivary glands, as in muscle (p. 178),
metabolic products given off during functional activity contribute
to the dilatation of the vessels. This is the simplest explanation of
the fact that the dilatation caused by chorda stimulation lasts longer
when saliva is being secreted than when the secretion has been
abolished by atropine.
The quantity of blood passing through the parotid of a horse
when it is actively secreting during mastication may be quadrupled
(Chauveau). The parallel between the muscle and the gland is
drawn closer when it is stated that electrical changes accompany
secretion (p. 838), and that the rate of production of carbon dioxide
and consumption of oxygen (in the submaxillary gland) is three or
four times greater during activity than during rest. The temperature
of the saliva flowing from the dog's submaxillary during stimulation
of the chorda has been found to be as much as 1-5° C. above that
of the blood of the carotid, although with the gland at rest no con-
stant difference could be detected between the arterial blood and
394 DIGESTION
the interior of Wharton's duct. But such measurements are open
to many fallacies; and while there is no doubt that more heat is
produced in the active than in the passive gland, it will not be
surprising, when the vastly-increased blood-flow is remembered,
that no difference of temperature between the incoming and out-
going blood has been satisfactorily demonstrated.
It has already been mentioned that most of the fibres of the chorda
tympani proper become connected with ganglion-cells, and lose their
medulla inside the submaxillary gland, only a few having already lost
it by a similar connection with ganglion-cells in the chordo-lingual
triangle. These facts have been made out by means of the nicotine
method previously described (p. 182). Thus, it is found that, after
the injection of nicotine (5 to 10 mg. in a rabbit or cat, 40 or 50 mg. in
a dog), stimulation of the chorda tympani proper or of the chordo-
lingual nerve causes no secretion from the submaxillary gland; but
stimulation of the hilus of the gland is followed by a copious secretion —
as much, if the stimulation is fairly strong, as was caused by excitation
of the nerve before injection of nicotine. That this is due neither to
any direct action on the gland-cells, nor to stimulation of the sympa-
thetic plexus on the submaxillary artery, but to stimulation of chorda
fibres beyond the hilus, is shown by the fact that after atropine has
been injected in sufficient amount to paralyze the nerve endings of the
chorda, but not of the sympathetic, stimulation of the hilus causes little
or no flow of saliva. The application of nicotine solution to the chordo-
lingual triangle does not affect the submaxillary secretion caused by
stimulation of the chordo-lingual nerve, even in cases where a few
secretory fibres for the submaxillary do not leave the chordo-lingual
nerve in the chorda tympani proper, but are given off to the chordo-
lingual triangle. This shows that none of the ganglion-cells in the
triangle are connected with the secretory fibres of the submaxillary
gland. By observations of the same kind they are known to be con-
nected with fibres going to the sublingual. In a similar way, by observ-
ing the effects of stimulation of the chorda on the bloodvessels before
and after the application of nicotine, it has been found that the vaso-
dilator fibres are connected with ganglion-cells in the same positions as
the secretory fibres (Langley).
Stimulation of the Sympathetic Fibres. — The sympathetic, as has
been already indicated, contains both vaso-constrictor and secretory
fibres for the salivary glands. If the cervical sympathetic in the
dog is divided, and the cephalic end moderately stimulated, a few
drops of a thick, viscid and scanty saliva flow from the submaxillary
and sublingual ducts, while the current of blood through the glands
is diminished. As a rule, no visible secretion escapes from the
parotid, but microscopic examination shows that many of the
ductules are filled with fluid, which is apparently so thick as to plug
them up (Langley) ; while the cells show signs of ' activity ' (p. 376).
Simultaneous Stimulation of Cranial and Sympathetic Fibres. —
When the chorda and sympathetic are stimulated together, the
former prevails so far, with moderate stimulation of the iatter, that
the submaxillary saliva is secreted in considerable quantity, and is
not particularly viscid. It is, however, richer in organic matter
than is the chorda saliva itself. When the chorda is weakly, and
INFLUENCE OF NERVOUS SYSTEM ON DIGESTIVE GLANDS 395
the sympathetic strongly, excited, the scanty secretion (if there is
any) is of sympathetic type, thick and rich in organic matter. With
strong stimulation of both nerves, the secretion, at first plentiful
and watery, soon diminishes, even below the amount obtained by
stimulation of the chorda alone, because of the diminution in the
blood-flow, and therefore in the oxygen-supply, produced by the
vaso -constrictors of the sympathetic (Heidenhain). With stimula-
tion just strong enough to cause secretion when applied separately
to either nerve, there is no secretion when it is applied simul-
taneously to both.
All this refers to the dog. In this animal, then, there seems to be
a certain amount of physiological antagonism between the secretory
action of the two nerves. But it differs in one respect from the
antagonism between their vaso-motor fibres; for with strong stimu-
lation the constrictors of the sympathetic always swamp the dilators
of the chorda, while the secretory fibres of the chorda appear upon
the whole to prevail over those of the sympathetic. And in all
probability this apparent secretory antagonism is very superficial,
and is due largely to the difference in the vaso-motor effects of the
two nerves. For it has been shown that, when the blood- flow
through the submaxillary gland is artificially diminished by gradu-
ated compression of its artery, stimulation of the chorda gives rise
to a thick, viscid and scanty saliva, relatively rich in organic solids
(Heidenhain). When the amount of blood passing through the
gland is made approximately the same as during stimulation of the
sympathetic, the chorda saliva becomes practically identical in
composition with the sympathetic saliva. This is one reason,
perhaps the chief one, why the sympathetic, when both nerves are
stimulated together, without artificial interference with the blood-
supply, always appears to add something to the common secretion
when there is a secretion at all, this something being represented
by an increase in the percentage of organic matter. The observation
that the sympathetic effect persists after stimulation has been
stopped, and that excitation of the chorda after previous stimula-
tion of the sympathetic causes a flow of saliva richer in organic
matter than would have been the case if the sympathetic had not
been stimulated, has long been considered a proof that the secretory
fibres of the two nerves are widely different in function. To explain
this result, Heidenhain assumed the existence in the sympathetic
of a preponderance of fibres concerned in the building up in the
cells of the organic constituents of the saliva (so-called ' trophic/
or, better, since the word ' trophic ' is usually associated with the
building up of the bioplasm itself, ' trophic-secretory ' fibres). It
would seem, however, that the increase in organic constituents is
only realized when a sufficient time has not been allowed, after
stimulation of the sympathetic, for the normal circulation to become
re-established in the gland. The saliva obtained by stimulation of
396 DIGESTION
the chorda immediately after a period of artificially diminished
blood-flow, without any previous excitation of the sympathetic,
also contains a surplus of organic matter (Carlson).
Indeed, the distinction between chorda and sympathetic saliva,
which, by taking account of the parotid as well as the submaxillary
and sublingual glands, has been generalized into a distinction
between cerebral and sympathetic saliva, and which, when the
vaso-motor conditions are left out of account, appears to hold good
in the dog and the rabbit, breaks down before a wider induction.
For in the cat the sympathetic saliva of the submaxillary gland,
although more scanty, is more watery than the chorda saliva
(Langley), which, however, is by no means viscid; and the two
secretions differ far less than in the dog. The discovery of Carlson
that the usual effect of stimulation of the cat's cervical sympathetic
with a weak interrupted current is a marked augmentation in the
blood-flow* through the submaxillary gland affords an explanation.
In accordance with this functional similarity, there is a much
smaller difference in the action of atropine on the two sets of fibres
in the cat than in the dog, although even in the cat the sympathetic
is less readily paralyzed than the chorda.
In their secretory action there is not even an apparent antagonism
in the cat, with minimal stimulation of both nerves, which causes
as much secretion as would be produced if both were separately
excited. Further, even in the dog, after prolonged stimulation of
the sympathetic, the submaxillary saliva is no longer viscid, but
watery, the proportion of solids, and especially of organic solids,
being much lessened, as it is also in chorda saliva after long excita-
tion. When the cerebral nerve of the resting gland is strongly
excited, it is found that up to a certain limit the percentage of
organic matter in a small sample of saliva subsequently collected
during a brief weak excitation increases with the strength of the
previous stimulation; this is also true of the inorganic solids. But
there is a striking difference when the experiment is made on a gland
after a long period of activity; here increase of stimulation causes
no increase in the percentage of organic material, while the inorganic
solids are still increased. In both cases the absolute quantity of
water, and therefore the rate of flow of the secretion, is augmented.
All this pojnts to the same conclusion as the microscopic appear-
ances in the gland-cells, that the cells during rest manufacture the
organic constituents of the secretion, or some of them, and store
them up, to be discharged during activity. The water and the
inorganic salts, on the other hand, seem rather to be secreted on
the spur of the moment, so to speak, and not to require such
elaborate preparation. And it has been stated that when the
* The increased blood-flow, which can be even better elicited by injection of
adrenalin, immediately succeeds the secretion of saliva, and seems to be due
not to the presence of vaso-dilator fibres in the sympathetic, but to metabolic
product*.
INFLUENCE OF NERVOUS SYSTEM ON DIGESTIVE GLANDS 397
chorda tympani is stimulated with currents of varying strength,
the quantity of organic substances in small samples of saliva
collected from a fresh gland is more nearly proportional to the rate
of secretion than is the quantity of water and salts, which varies
also with the blood-supply.
Lest the apparently insignificant result of artificial stimulation
of the sympathetic in such animals as the dog should cause its
secretory action to be aopraised at too low a value, it should be
remembered that in me intact body the sympathetic secretory fibres,
when they are excited, are, it may be assumed, excited independently
of the vaso-constrictors, and even in conjunction with the vaso-
dilators'of the salivary glands.
It is conceivable that such differences between chorda and
sympathetic saliva as are not accounted for by the differences in
the blood-flow during their stimulation are due, not to the nerve
fibres, but to the end organs with which they are connected; that
is, the two nerves may supply, not the same, but different gland-
cells. And it is well known that even after prolonged stimulation
of the chorda or chordo-lingual alone, some alveoli of the dog's
submaxillary gland remain in the ' resting ' state ; after stimulation
of the sympathetic alone, the number of unaffected alveoli is much
greater; while after stimulation of both nerves, few alveoli seem
to have escaped change. If there is no essential difference between
the cranial and sympathetic secretory fibres, it is easy to understand
that they will be distributed to different secreting elements. The
supposed proof that there must be some overlapping in the nerve-
supply — i.e., that some cells must be supplied from both sources,
since excitation of the sympathetic influences the amount of organic
material in the saliva obtained by subsequent stimulation of the
chorda — is, as we have just seen, by no means so cogent as has been
assumed. And, indeed, we know nothing of a division of labour
between the cells of a gland, except when there are obvious anatom-
ical distinctions. Thus, the submaxillary gland in man contains
both serous and mucous acini, and mucin-making cells are scattered
over the ducts of most glands, and, indeed, on nearly every surface
which is clad with columnar epithelium. In these cases we cannot
doubt that one constituent — mucin — of the entire secretion is manu-
factured by a portion only of the cells. In the cardiac glands of the
stomach, too, the ovoid cells, in all probability, yield the whole of
the acid of the gastric juice. But, so far as we know, every hepatic
cell is a liver in little. Every cell secretes fully-formed bile ; every
cell stores up, or may store up, glycogen. So it is with the secretory
alveoli of the pancreas, if we consider the islands of Langerhans as
having no connection with the alveoli; one cell is just like another;
all apparently perform the same work; each is a unicellular pan-
creas. (See p. 638.)
Paralytic Secretion. — When the chorda tympani is divided, a slow
' paralytic ' secretion from the submaxillary gland begins in a few
398 DIGESTION
hours, and continues for a long time accompanied by atrophy of the
gland. There is also a secretion of the same kind from the submaxillary
on the opposite side, but it is less copious. This is called the ' antilytic '
secretion, which is most pronounced in the first few days after the
operation, and seems to be a transient phenomenon. It can be at once
abolished by section both of the chorda and the sympathetic on the
corresponding side, ana is therefore due to impulses arising in the
central nervous system. The cause of the paralytic secretion has not
been fully made out. If within two or three days of division of the
chorda the sympathetic on the same side is cut, the secretion is greatly
diminished or stops altogether; and it is concluded that up to this time
it is maintained by impulses passing along the sympathetic to the gland
from the salivary centre, the excitability of which has been in some way
increased by division of the chorda, possibly by some such degenerative
process in the cells as the changes seen in cerebro-spinal motor cells
whose axons have been divided (p. 858). This may also account for the
antilytic secretion. But if section of the sympathetic is not performed
for several days, it has no effect on the paralytic secretion, which at
this stage seems to depend on local changes in or near the gland itself,
leading to a mild continuous excitation of those nerve-cells on the
course of the fibres of the chorda to which reference has already been
made. Section of the sympathetic alone causes neither secretion nor
atrophy, nor does removal of the superior cervical ganglion. The
histological characters of the gland-cells during paralytic secretion are
those of ' rest.'
Reflex Secretion of Saliva. — The reflex mechanism of salivary
secretion is very mobile, and easily set in action by physical and
mental influences. It is excited normally by impulses which arise
in the mouth, especially by the contact of food with the buccal
mucous membrane and the gustatory nerve-endings. The mere
mechanical movement of the jaws, even when there is nothing
between the teeth, or only a bit of a non-sapid substance like india-
rubber, causes some secretion. The vapour of ether gives rise to a
rush of saliva, as does gargling the mouth with distilled water.
The smell, sight, or thought of food, and even the thought of saliva
itself, may act on the salivary centre through its connections with
the cerebrum, and make ' the teeth water.' A copious flow of
saliva, reflexly excited through the gastric branches of the vagus,
is a common precursor of vomiting. The introduction of food into
the stomach also excites salivary secretion.
The researches of Pawlow and his pupils have shown that the
salivary glands are not excited indifferently by everything which
comes into contact with the buccal mucous membrane. A remark-
able adaptation exists between the properties of food or foreign
bodies introduced into the mouth and their effects upon the secre-
tion of saliva. When solid dry food is given to a dog saliva is
copiously poured out; much less is secreted when the food is moist.
Acids or salts induce an abundant flow, in order that they may
be neutralized, diluted or washed out of the mouth. In this case
a watery liquid, poor in mucin, flows from the mucous glands.
Mucin is a lubricant to facilitate the swallowing of solid food, and
INFLUENCE OF NERVOUS SYSTEM ON DIGESTIVE GLANDS 399
here it could be of no use. When clean pebbles are put in the dog's
mouth the animal may try to chew them, but eventually ejects
them. Either no saliva or very little is secreted, since it could
not aid in their expulsion. If, however, the very same stones are
reduced to sand and again introduced into the animal's mouth,
saliva is plentifully secreted to wash it out.
The serous and mucous salivary glands are not necessarily excited
by the same food materials, and here again we can trace an astonish-
ingly exact adaptation. A permanent parotid or submaxillary
fistula can easily be made in a dog by freeing Stenson's or Wharton's
duct from the surrounding mucous membrane for a little distance,
bringing the natural orifice of the duct out through a small wound
in the cheek, and stitching it in position there. When it is desired
to collect saliva, the wide end of a funnel-shaped tube, whose stem
is bent so as to hang vertically, can be attached by a little shellac
of low melting-point to the skin around the orifice of the duct and
at some distance from it, and on the narrow end can be hung a small
graduated tube, into which the saliva drops. When fresh meat is
given to the animal little or no parotid saliva is secreted, while a
copious flow takes place from the submaxillary gland, mucin being
required to lubricate it for deglutition, while water is not specially
needed. But if the meat is in the form of a dry powder the parotid
pours out a plentiful secretion, while the submaxillary also secretes
a fluid relatively rich in mucin. The same difference is seen between
fresh moist bread and dry bread. The afferent nerve-endings from
which impulses are carried to the reflex centres (or the portions of
the salivary centre) which preside over the various salivary glands
must possess the power of very delicate selection as regards the
kinds of stimulation by which they are affected. The mere relish
of the animal for the different kinds of food plays but a small part.
Most dogs display a much livelier interest in a piece of meat than
in a piece of dry biscuit, yet it is the biscuit which excites the parotid
to activity.
The sight of dry food causes an abundant flow of watery saliva
from the parotid, and a flow of fluid rich in mucin from the sub-
maxillary. Various uneatable substances, including substances
which in contact with the mucous membrane of the mouth produce
strong and disagreeable stimulation of it, and excite disgust, cause
also, when viewed from a distance, secretion by all the salivary
glands; but the submaxillary saliva, as ought to be the case for
substances unfit for food, and therefore not destined to be swallowed,
is poor in mucin. When the animal is shown pebbles and sand
the phenomena are qualitatively the same as when they are put
into its mouth — the glands remaining inactive in presence of
the pebbles, but secreting plentifully at sight of the sar^d. In
short, the same adaptation is observed in the case of the so-called
psychical secretion as when the stimulating substances act directly
4oo DIGESTION
upon the endings of the afferent salivary nerves in the buccal
mucous membrane. It is further worthy of note that when the
animal is hungry the psychical secretion is most copious and most
easily obtained. After a full meal it cannot be excited at all.
When food (or other exciting substance) is repeatedly shown to a
fasting animal the reaction becomes each time weaker, and finally
the glands cease to respond. All that is then necessary to restore
the reaction is to put into the animal's mouth a little of the food
(or other object) . When it is now shown it at a distance the ordinary
effect follows promptly. This indicates that the condition of the
salivary centre exercises an important influence upon the psychical
secretion, its excitability to the weaker stimulus set up by the sight
of the object being increased by the stronger reflex stimulation
coming directly from the mouth. In the condition of satiety the
inexcitability of the centre may be due to the action of food-
products in the blood.
In most animals and in man the activity of the large salivary
glands is strictly intermittent. But the smaller glands that stud
the mucous membrane of the mouth never entirely cease to secrete,
and the same is the case with the parotid in ruminant animals.
The centre is situated in the medulla oblongata, stimulation of
which causes a flow of saliva. The chief afferent paths to the
salivary centre are the lingual branch of the fifth and the glosso-
pharyngeal ; but stimulation of many other nerves may cause reflex
secretion of saliva. In experimental reflex stimulation, the sole
efferent channel seems to be the cerebral nerve-supply of the glands.
After section of the chorda, no reflex secretion by the submaxillary
gland can be caused, although the sympathetic remains intact.
It was alleged by Bernard that, after division of the chordo-
lingual, a reflex secretion could be obtained from the submaxillary
gland by stimulating the central end of the cut lingual nerve between
the so-called submaxillary ganglion and the tongue, the ganglion
being supposed to act as ' centre.' It has been shown, however, that
this is not a true reflex effect, but is due to the excitation of certain
(recurrent) secretory fibres of the chorda that run for some distance
in the lingual, then bend back on their course and pass to the gland.
It may be in part a pseudo- or axon-reflex (p. 913), elicited by
excitation of efferent fibres, which send branches to some of the
ganglion-cells.
The salivary centre can also be inhibited, especially by emotions
of a painful kind — for instance, the nervousness which often dries
up the saliva, as well as the eloquence, of a beginner in public
speaking, and the fear which sometimes made the medieval ordeal
of the consecrated bread pick out the guilty.
In rare cases the reflex nervous mechanism that governs the
salivary glands appears to completely break down; and then two
opposite conditions may be seen — xerostomia, or ' dry mouth,' in
INFLUENCE OF NERVOUS SYSTEM ON DIGESTIVE GLAtiDS 46!
which no saliva at all is secreted, and chronic ptyalism, or hydro-
stomia, where, in the absence of any discoverable cause, the amount
of secretion is permanently increased. Both conditions are said
to be more common in women than in men.
The Influence of Nerves on the Gastric Glands. — Like saliva, gastric
juice is not secreted continuously, except in animals such as the
rabbit, whose stomachs are never empty. The normal and most
efficient stimulus is the eating of food and its presence in the
stomach. Mechanical stimulation of the gastric mucous membrane
with a non-digestible substance, such as a feather or a glass rod,
causes secretion of mucus, but not of gastric juice. But the
observations mentioned above on the difference of response of the
salivary glands to different substances suggest that the local mechan-
ical stimulation of the food on the gastric glands may be more
effective. There is also at first thought much to indicate that the
gastric glands are stimulated chemically in a more direct manner
than the salivary glands by the local action of food substances
reaching the cells by a short-cut from the cavity of the stomach,
or in a more roundabout way by the blood. And it might be very
plausibly argued that the gastric glands are favourably situated
for direct stimulation, while the large salivary glands are not ; and
that the great function of saliva being to aid deglutition, an almost
momentary, and at the same time a perilous act, it is necessary to
provide by a nervous mechanism for an immediate rush of secre-
tion at any instant, while it is not important whether the gastric
juice is poured out a little sooner or a little later, and therefore it is
left to be called forth by the more tardy and haphazard method of
local action. Nevertheless, on looking a little closer, we find that
this does not exhaust the subject, and that the gastric secretion
can be influenced by events taking place in distant parts of the
body, just as the salivary secretion can. In a boy whose oesophagus
was completely closed by a cicatrix, the result of swallowing a strong
alkali, and who had to be fed by a gastric fistula, it was found
that the presence of food in the mouth, and even the sight or smell
of food, caused secretion of gastric juice (Richet).
Here there must have been some nervous mechanism at work.
The secretion cannot have been excited by the direct action of
absorbed food-products circulating in the blood — an explanation
which might be given, though an insufficient one, of the secretion
seen in an isolated portion of the cardiac end of the stomach during
the digestion of food in the rest. The efferent nervous channels
through which these effects are produced have been defined by
Pawlow's experiments on dogs. He first made a gastric fistula,
then a few days afterwards divided the oesophagus through a
wound in the neck, and stitched the two cut ends to the edges of
the wound. After the animals had recovered, it was observed that
when meat was given to them by the mouth, a copious secretion of
402
DIGESTION
Py/oru.
Plexus gast
anterior
gastric juice followed in five or six minutes, notwithstanding the
fact that in this ' sham feeding ' the food immediately escaped from
the opening in the upper portion of the divided oesophagus. Much
the same result was seen when the food was simply shown to the
animal. Indeed, when a hungry animal is tempted with the sight
of meat, the flow of gastric juice, always occurring after a latent
period of five or six minutes, may be even greater than with sham
feeding. Division of the splanchnic nerves had no effect on this
reflex secretion, while it could not be obtained after division of both
vagi below the origin of their cardiac and pulmonary branches, by
which disturbance of the heart and respiration are avoided.
Further, stimulation of the peripheral end of the vagus in the neck*
caused secretion. These experiments show that secretory fibres
for the gastric glands run in the vagi. It is probable that the vagi
also contain
efferent fibres
which inhibit
ophagus ,
the gastric
Plexus gastn'eus T,, '
posterior vagi, secretion. 1 ne
excitation of
the secretory
fibres is not
produced re-
flexly by the
processes of
mastication
and deglutition
as such. Di-
lute acid is the
most powerful
chemical stim-
ulus for the
buccal mucous
membrane, and
when it is introduced into the mouth of a dog with a double
cesophageal and gastric fistula, an abundant secretion of saliva at
once ensues. But no matter how long the animal continues to
swallow the mixture of saliva and acid, no gastric juice is formed.
The same is the case in sham feeding with salt, pepper, mustard,
smooth stones, and even extract of meat. It is the desire for food
—the appetite, as we call it — and the feeling of satisfaction associa-
ated with eating food that the animal relishes, which is the efficient
cause of the gastric secretion in sham feeding. The more eagerly
the dog eats, the greater is the flow of gastric juice.
* The nerve was not stimulated till a few days after the section, so as to
allow the cardio-inhibitory fibres to degenerate. Otherwise the heart would
have been stopped by the stimulation.
Fig. 161. — Pawlow's Stomach Pouch. AB, line of incision;
C, flap for forming the stomach pouch. At the base of 'the
flap the serous and muscular coats are preserved, and only
the mucous membrane divided, so that the branches of the
vagus going to the pouch are not severed.
INFLUENCE OF NERVOUS SYSTEM ON DIGESTIVE GLANDS 403
rosa
cularis
Pawlow also performed the converse experiment. In dogs in
which a pouch had been isolated from the stomach and made to
open to the exterior by the surgical procedure illustrated in Figs. 161
and 162, he introduced into the large stomach, without the animal's
knowledge, food of various kinds. This is best done in a sleeping
dog. The secretion of gastric juice, both in the main stomach and
in the pouch or miniature stomach", which is known in a great
variety of conditions to present an exact picture of the process of
secretion in the large, is markedly delayed and scanty when it does
appear. Bread and coagulated egg-white did not yield a single
drop during
the first hour
or more. Raw
flesh excited a
secretion, but
after an inter-
val of fifteen
to forty - five
minutes, in-
stead of five
or six to ten,
as in sham
feeding. It was
very scanty
during the
first hour
(only o n e -
third the nor-
mal amount),
and possessed
a very low di-
gestive power.
The impor-
tance of the
psychical ele-
ment is shown by the fact that in one dog, which, after a weighed
amount of meat had been introduced into its stomach (without its
knowledge), received a sham meal of meat, the amount of protein
digested after one and a half hours was five times greater than in
another animal treated exactly in the same way, except that the sham
meal was omitted. But even after division of the vagi, gastric secre-
tion is still caused by the introduction of various substances into the
stomach, especially water and meat extract. The active substances
in the meat extract are, for the most part, insoluble in alcohol.
Kreatin is inactive. It is in virtue of these substances that raw
meat placed directly in the stomach causes some secretion after a
Fig. 162. — Pawlow's Stomach Pouch. S, the completed pouch;
V, cavity of stomach.
4°4 DIGESTION
time. Milk and gelatin solution are also direct excitants of gastric
secretion apart from the water in them. Starch, fat, and egg-white
are totally inert. After section of both vagi in dogs, no marked
qualitative or quantitative changes have been observed in the
gastric juice. The secretion caused by the presence of food in the
stomach is still obtained when, in addition to the vagi, all other
nerves which can possibly connect the central nervous system with
the organ have been severed and the sympathetic abdominal
plexuses have been destroyed (Popielski). We must therefore sug-
pose that the gastric glands, while normally under the control of a
nervous mechanism in the upper portion of the cerebro- spinal axis
whose efferent fibres run in the vagi, are also capable of being locally
stimulated throug!i the peripheral ganglia in the stomach walls or
the chemical action of the products of digestion absorbed into the
blood. Edkins showed that the injection of food substances or the
products of their digestion (broth, dextrin, peptone) or of acid into
the blood caused no secretion of gastric juice, while the injection
of an extract of the pyloric mucous membrane, made by boiling it
with water, acid, or peptone, excited a certain amount of secretion.
He therefore concluded that the secondary secretion of gastric juice
is determined, not by local stimulation of a reflex mechanism in the
gastric wall, but by the production in the mucous membrane of the
pyloric end of a chemical substance, the gastric secretin or gastric
hormone,* which is absorbed by the blood, and acts as an excitant
to all the gastric glands. The cardiac mucosa was found incapable
of forming this substance.
It is not to be imagined that the ' psychical ' secretion and the
secretion called forth by the direct action of the food or food-
products in the stomach perform independent offices. They can,
in various instances, be shown to supplement each other. For
example, not more than one-half or one-third of the gastric juice
secreted during the digestion of bread or boiled egg-albumin can
be ascribed to the psychic effect. Yet these substances, when
introduced directly into the stomach, cause practically no secretion.
We must suppose that during the digestion of the bread and albu-
min by the psychically secreted juice certain products analogous to
those in the meat extract are formed, which act as chemics.1 excitants
of the local secretory apparatus. The psychic juice is indispensable
in this case to start the process, ' to set the stove ablaze,' as Pawlow
puts it. In the case of meat it is not indispensable, since the meat
can chemically excite the gastric glands; but it greatly hastens the
process of digestion. These facts emphasize the importance of
* ' Hormone ' (from 6p/taw, I arouse or excite) is the name given to a sub
stance which, carried by the blood from the place where it is formed, acts as
a chemical messenger in exciting the activity of some more or less distant
organ. The classical example is the pancreatic secretin which, manufactured
in the intestinal mucosa, excites the secretion of the pancreatic juice.
INFLUENCE OF NERVOUS SYSTEM ON DIGESTIVE GLANDS 405
appetite in digestion, a truism in treatment which thus receives
for the first time a rational explanation. The influence of good-
humour upon nutrition, which experience has crystallized into the
proverb ' Laugh and grow fat,' has also been shown to depend —
in great part, at least — upon a beneficial action on the digestive
functions, both motor and chemical. The movements of a cat's
stomach and intestines have been observed to cease when the
animal became angry or excited by unpleasant emotions; and in a
dog whose gastric glands were pouring out a copious psychical
secretion in response to a sham meal, secretion stopped abruptly
when the animal's wrath was awakened by what is probably to the
normal dog the most specifically ' adequate ' stimulus for the emotion
of anger — the sight of a cat which he was restrained from chasing.
By means of experiments with the miniature stomach it has been
further shown. that each kind of food has its own characteristic
curve of gastric secretion. With flesh diet the maximum rate of
secretion occurs during the first or second hour, and in each of the
first two hours the quantity of juice furnished is approximately
the same. With bread diet we have always a sharply-indicated
maximum in the first hour, and with milk a similar one during the
second or the third hour (Fig. 163). The juice secreted on different
diets also differs in digestive power — i.e., in the amount of protein
which a given quantity of it will digest in a given time. ' Bread
juice ' is much stronger in ferment than ' meat juice/ and ' meat
juice ' somewhat stronger than ' milk juice ' (Fig. 164). But
' meat juice ' has a higher acidity than ' bread juice,' ' milk juice '
being intermediate. These differences do not necessarily indicate
that the gastric mucous membrane responds in a specific way to
each kind of food substance, as suggested by Pawlow. They may
depend on several circumstances, and particularly on this — that the
quantity, though not the quality, of the psychical or ' appetite '
juice is related to the relish with which the animal eats the food.
The products formed in the digestion of the different foods by the
psychical juice may therefore be different in nature and amount,
and thus the quantity of the gastric hormone which determines the
secondary secretion may vary with the food.
The young mammal, like the adult, secretes gastric juice before
the food reaches the stomach. In puppies from one to eighteen
days old sham feeding (sucking the teats of the mother after'an
oesophageal fistula has been made in the younger animals and a
double oesophageal and gastric fistula in the older) causes a liquid
with the properties of gastric juice to gather in the stomach. This
power, then, is a congenital one. The individual does not gain it
by experience; it comes into the world with him (Cohnheim).
The Influence of Nerves on the Pancreas. — Like the stomach, the
pancreas receives secretory fibres through the vagus. These are
406
DIGESTION
45678 » 23456 789101 23456
probably connected with a reflex centre in the medulla oblongata.
It has long been known that when the medulla is stimulated a flow
of pancreatic juice is occasionally set up, or is increased if already
going on. The same is true when the vagus is stimulated in the
ordinary way in the neck. But the experiment often failed, for
the pancreas
is peculiarly
susceptible
to circulatory
disturbances,
and stimula-
tion of the
bulb or the
vagus may
interfere with
the blood-
flow through
the gland by
exciting its
vaso-con-
strictor fibres or causing inhibition of the heart. These disturbing
influences may be avoided, as Pawlow has shown, by stimulating the
vagus, three or four days after dividing it, with slowly-recurring
stimuli (induction shocks or light blows from a small hammer
worked by an
Flesh, 200 grm.
Bread, 200 grm.
Milk, 600 c.c.
Fig. 163. — Rate of Secretion of Gastric Juice with Diets of Meat,
Bread, and Milk (Pawlow).
electro - mag- H°urs
10.0
net at the
rate of about t go
one in the «j
second). The £| e,o
secret or y ^3
fibres are still ° « *.°
susceptible of J
excitation,
while the car- c
dio-inhibitory
fibres, which
degenerate Fig. 16-
more rapidly. digest
i *_. protei
are almost or nour>
altogether in-
2345678234 5678923456
/
^
i
i
\
\
^
— _
— '
/
\
f
S
\
__
^
\
/
\
/
\
/
\
^--
j ^ j ^
Flesh, 200 grm. Bread, 200 grm. Milk, 600 c.c.
).. — Digestive Power of Gastric Juice (Pawlow). The
ive power of the juice, as measured by the length of the
n column digested in Mett's tubes, is represented hour by
with diets of flesh, bread, and milk.
excitable, and the vaso-constrictors are but little affected by
these slow rhythmical stimuli, which excite the secretory nerves
(p. 175). A pancreatic fistula has previously been established by
excising a small portion of the duodenal wall containing the open-
ing of the pancreatic duct, closing the intestine by sutures, and
I NFL UENCE OF NER VO US S YSTEM ON DIGEST I VE GLA NDS 407
stitching the orifice of the duct into the abdominal wound. On
stimulation of the vagus the juice will begin in two to three minutes
to drop from a cannula in the duct, and will continue to flow for
several minutes after cessation of the stimulus. The sympathetic
also contains secretory fibres for the pancreas. Efferent fibres
which inhibit the secretion have been also discovered in the vagus.
Their presence may be most clearly demonstrated when that nerve
is stimulated during the flow of pancreatic juice excited by the
introduction of dilute acid into the duodenum. Stimulation of the
central end of the vagus and oi the other nerves is capable of
reflexly inhibiting
the pancreatic secre-
tion. Painful im-
pressions have a
strong inhibitory in-
fluence. This is one
of the reasons why
many observers
failed to detect the
secretory nerves.
The inhibition
caused by vomiting
is probably due to
impulses ascending
the vagus. It is pos-
sible that through
these nervous chan-
nels the pancreatic
secretion is affected
by the psychical con-
ditions connected
with eating and the
desire for food, just
as in the case of the
gastric secretion ; but
our information on
this subject is scantier and less precise. A flow of juice may un-
doubtedly take place within three or four minutes after food is taken,
but it is not quite certain whether this is not determined by the
passage of some of the acid gastric contents into the duodenum.
Secretin. — We have already referred to the fact that pancreatic
secretion is excited by the presence of acid in the duodenum. The
mechanism of this action is of great interest. Two or three minutes
after the introduction of 0-4 per cent, hydrochloric acid into the
duodenum, pancreatic juice begins to flow. A similar effect is seen
when the acid is placed in the jejunum, but not when it is injected
Fig. 165. — Secretion of Pepsin. C shows the quantity
of pepsin(ogen) in the mucous membrane of the
cardiac end of the stomach at different times during
digestion; P, the quantity of pepsin(ogen) in the
mucous membrane of the pyloric end ; S, the quantity
of pepsin in the secretion of the cardiac glands. The
numbers marked along the horizontal axis are hours
since the last meal. About five hours after the
meal, S reaches its maximum. From the very be-
ginning of the meal C falls steadily down to the
tenth hour, and then begins to rise — i.e., the gland-
cells of the cardiac end of the stomach become
poorer in pepsin(ogen) as secretion proceeds.
403 DIGESTION
into the lower part of the ileum. It is obtained as strongly and as
promptly from an isolated loop of intestine when all the nerves
passing to it have been cut, and the solar plexus extirpated, and also
after the administration of atropine, which paralyzes the endings of
secretory nerves elsewhere. The secretion accor lingly does not
depend upon a local reflex mechanism, with its afferent endings in
the intestinal mucous membrane, but upon some substance which is
carried to the pancreas by the blood, and acts directly upon its cells.
This substance is not the acid, for the injection of 0-4 per cent,
hydrochloric acid into the blood produces no effect upon the pan-
creas. It has been shown by Bayliss and Starling that the exciting
substance is a diffusible body of low molecular weight, probably of
organic nature, but not a protein, which they call secret in. It is
soluble in alcohol or alcohol and ether, and is not destroyed by
boiling. It is produced in the mucous membrane of the jejunum or
duodenum on exposure to dilute hydrochloric acid. Extracts of
mucous membrane so treated cause a copious pancreatic secretion,
and a smaller secretion of bile, when injected in small quantities into
the blood of animals in which no such secretion is taking place, but
have no influence on any other gland. At the same time the arterial
blood-pressure falls somewhat. The substance which produces the
fall of blood-pressure is different from secretin, since acid extracts
of the lower end of the ileum, which have no effect on the flow of pan-
creatic juice, diminish the blood-pressure. A precursor of secretin,
called pro-secretin, exists in the intestinal mucous membrane, and
can be extracted from it by physiological salt solution. ' It does not
affect the pancreatic secretion. By boiling or by the action of acid
secretin is split off from it. Pro-secretin is most abundant in the
duodenum, and diminishes as we pass down the .intestine.
Secretin is very widespread in the animal kingdom. In the
monkey, dog, cat, rabbit, man, ox, sheep, pig, squirrel, goose,
tortoise, salmon, dog-fish, and skate evidence of its presence has
been obtained. The secretin of one animal will excite a flow of pan-
creatic juice in an animal of a different kind as well as in one of the
same kind. In normal digestion secretin is formed under the
influence of the acid chyme, not in the stomach, but after it has
passed into the duodenum. The passage of the chyme through the
pylorus, as previously mentioned (p. 337), is regulated by the re-
action of the duodenal contents, as well as by the consistence of the
gastric contents. So long as the liquid in the duodenum is acid, the
pylorus remains closed. As soon as the first small portion of acid
chyme ejected from the stomach has been neutralized by the in-
creased secretion of the pancreatic juice and the outpouring of bile
from the gall-bladder in response to the stimulus of the acid, the
pylorus opens again.
According to Pawlow, certain food substances, notably fat, and
I NFL UENCE OF NER VO US S YSTEM ON DIGESTI VE GLANDS 409
water stimulate the pancreatic secretion, and with great promptness,
even before any acid has been produced in the stomach, and there-
fore before any can have passed into the duodenum. Possibly this
effect is elicited through the long reflex paths already described as
running in the vagi or through a local nervous mechanism, which,
although it does not take part in the excitation of the pancreatic
secretion by acid, may yet exist for the performance of other offices.
It is more probable, however, that it is due to the passage of some of
the gastric contents through the pylorus; for when oil is introduced
into the small intestine, it causes the production of secretin, although,
unlike dilute acid, it is quite ineffective in forming secretin when
rubbed up with the scraped-off mucous membrane. That secretin
acts on the pancreatic cells in a different way from the secretory
nerve fibres contained in the vagus is indicated by the difference in
the characters of the juice secreted under the influence of the two
mechanisms. The nervous secre-
tion is thick and opalescent, rich
in enzymes, including trypsin in
the active form, and proteins, but
its alkali content is low. Like
other secretions excited through
nerves, it is inhibited by atropine.
The chemical secretion due to
secretin, is thin and watery, rich Fi«- 166.— Rate of Secretion of Pan-
n v • j creatic Juice. S shows the variation
in alkalies, poor in proteins and in the rjate o{ secretion of the pan.
in enzymes, and among the latter, creatic juice in a dog; P, the varia-
trypsin occurs only in the inactive tion in the percentage of solids in
/c ., •, x the juice. It will be seen that the
n ^awitSCnj. < maxima of S fall at the same time
The pancreatic, like the gastric, as the maxima of P. The numbers
juice is said to vary as regards alonS the horizontal axis are hours
j-. _,• /• •,T~ ,-u since the last meal,
its digestive properties with the
nature of the food. On a diet of bread the juice is very poor
in fat-splitting ferment, while on a diet of flesh it is richer, and
on a diet of milk richest of all. With bread the juice is relatively
rich in amylolytic ferment. When we take the quantity of the
juice as well as its strength in ferments into consideration, it is
stated that bread occasions the secretion of a juice with a greater
quantity of proteolytic ferment than either milk or meat, although
it is relatively dilute (Fig. 169). The vegetable proteins require
more ferment to digest them than proteins of animal origin. * There
is no more evidence that the adaptation of the pancreatic juice to the
nature of the food is due to a specific sensibility of the duodenal
mucosa to the various food-stuffs than there is in the case of the
adaptation of the gastric juice. If the volume of the chyme and its
acidity are related to the nature of the food, then the amount of
secretin formed, and therefore the intensity of secretion in the
4io DIGESTION
pancreag, will be similarly related. The one apparently proved
example of specific adaptation of the pancreatic juice has not stood
the test of a critical examination. It was asserted that in dogs fed
for some days with food containing lactose (milk) the ferment,
lactose, is present in that secretion, while the pancreatic juice of
dogs whose food is free from lactose does not contain lactase. The
adaptation of the pancreas to lactose was supposed to be achieved
through some substance produced by the action of lactose on the
i n in iv v i M in iv vviviivmi ii in iv v vi intestinal mucous
membrane, which
plays the part of
a specific chemical
stimulus to the
pancreatic cells or
their secretory
nervous mechan-
ism, causing them
to form lactase.
But it has been
conclusively shown
that when dogs
are fed with lac-
tose for weeks no
lactase appears in
the pancreatic
juice (Plimmer).
The natural se-
cretion of pan-
creatic juice is by
no means so inter-
mittent as that of
saliva. In the rab-
bit the pancreatic,
like the gastric,
juice flows con-
tinuously. In the
dog it begins al-
most as soon as
food is taken, rises in two or three hours to a maximum, then
faUs till the fifth or sixth hour, after which it may mount 'again
somewhat, and then, gradually diminishing, ultimately stops (Figs
166, 167) . D uring normal activity the bloodvessels of the gland are
dilated. But under experimental conditions the increased secretion
caused by secretin is accompanied sometimes by an increase and
sometimes by a diminution in the blood-flow, and secretion may
continue for some time after complete cessation of the circulation
Flesh, 100 grm. Bread, 250 grm.
Milk, 600 grm.
Fig. 167. — Secretion of Pancreatic Juice with Different
Diets (Pawlow). The hours are in roman numerals.
I NFL UENCE OF NER VO US S YSTEM ON DIGESTI VE GLA NDS 411
while the increased consumption of oxygen which goes hand in hand
with the increased secretion is also independent of the blood-supply
(May, Barcroft and Starling). This shows how far the secretory pro-
cess is from a mere mechanical nitration, although it does not follow
that, under normal conditions, a decreased blood-flow ever does
accompany an increased secretion. There is one difference between
the normal secretion of pancreatic juice and of saliva which may still
be mentioned : the pressure of the latter in the submaxillary duct may,
as we have seen, greatly exceed the arterial blood-pressure, without
reabsorption and consequent oedema of the gland occurring ; but the
secretory pressure of the pancreatic cells is very low, not more than
a tenth of that of the salivary glands.
(Edema begins before a manometer in
the duct shows a pressure of 20 mm.
of mercury, the secreted fluid passing
very easily into the lymph spaces.
The mutual relations of the spleen
and pancreas have formed the subject
of numerous inquiries. Some authors
maintain that the spleen plays an im-
portant role in the elaboration of the
proteolytic ferment of the pancreas,
forming a substance which we may call
pro-trypsinogen, since it is supposed to
be carried in the blood to the pancreatic
cells, and changed by them into trypsin-
ogen. There is some evidence that
extracts of the spleen prepared from it
when congested during digestion exert a
favourable influence on the proteolytic
power of the pancreas (Mendel). And
there is no doubt that the spleen, like
other organs, contains an intracellular
enzyme which can aid in the digestion
of protein. The products of the action
in an acid medium of this enzyme are the same as those formed by
trypsin in an alkaline medium (Leathes). But this is not enough to
prove that the spleen has any special relation to pancreatic digestion.
The Influence of Nerves on the Secretion of Bile. — Although bile is
secreted constantly, it only passes at intervals into the intestine.
For the liver in many animals, unlike every other gland except the
kidney, has in connection with it a reservoir, the gall-bladder, in
which its secretion accumulates, and from which it is only expelled
occasionally. We have therefore to distinguish the bile- secretion
from the bile-expelling mechanism. To study the rate of secreting
of bile (Fig. 168), a fistula of the gall-bladder can be established.
Fig. 168.— Rate of Secretion of
Bile. S shows how the rate of
secretion of bile falls in a dog
when a biliary fistula is first
made, and the bile thus pre-
vented from entering the intes-
tine ; P shows the fall of the per-
centage of solids. The numbers
along the horizontal axis are
quarters of an hour since bile
began to escape through the
fistula. The numbers along
the vertical axis refer only to
curve S, and represent the rate
of secretion in arbitrary units.
412 DIGESTION
But to learn the function of bile in digestion it is more important
to know when and at what rate it enters the intestine. For this
purpose a fistula is made by cutting the natural orifice of the common
bile-duct with a piece of the surrounding mucous membrane out of
the intestine and transplanting it upon the serous coat, where it is
sutured. The loop of intestine, with the orifice of the duct facing
outwards, is then stitched into the abdominal wound, where it is
allowed to heal. Of course, since a circulation of the bile-acids
takes place — i.e., an absorption from and r^ -excretion into the
intestine — the formation of that juice cannot proceed upon abso-
lutely normal lines when the bile no longer enters the duodenum.
The only condition under which fistula bile could have the same
composition as normal bile would be that in which as great an
amount of bile-acids is introduced into the gut as escapes through
the fistula. A circulation of a smaller proportion of the bile-pig-
ments is also probable. A circulation of the biliary cholesterin is
denied by some observers (Stadelmann) but affirmed by others. It
is certain that cholesterin is of importance in the body, and if the
supply of sterins (p. 570) in the food is insufficient it is to be sup-
posed that some of the biliary cholesterin would be used over again.
Of the direct influence of nerves, either on the secretion of bile or on
its expulsion, we have scarcely any knowledge, scarcely even any guess
which is worth mentioning here. It is true the secretion of bile may
be distinctly affected by the section and stimulation of nerves which
control the blood-supply of the stomach, intestines, and spleen, for the
quantity of blood passing by the portal vein to the liver depends upon
the quantity passing through these organs, and the rate of secretion is
diminished when the blood-supply is greatly lessened. In this way
stimulation of the medulla oblongata, the spinal cord, or the splanchnic
nerves stops or slows the secretion of bile by constricting the abdominal
vessels ; and the same effect can be reflexly produced by the excitation
of afferent nerves.
The right splanchnic nerve contains inhibitory with some motor
fibres, and the vagi (especially the left) contain motor fibres for the
gall-bladder. Probably its contraction takes place naturally in
response to reflex impulses from the mucous membrane of the duo-
denum, for the application of dilute acid to the mouth of the bile-
duct causes a sudden flow of bile,* and the acid contents of the
stomach, when projected through the pylorus into the intestine,
have a similar effect. But, in addition, as we have seen, the secretin
formed will cause an increase in the rate of secretion of the bile. In
studying the effect of secretin it is necessary to obtain it free from
bile- salts, since these cause of themselves an increased secretion of
bile. When this is done by dissolving out with alcohol any bile-salts
which may be present in the extract of intestinal mucous membrane,
* This result seems to be difficult to realize experimentally. Bainbridge
and Dale could not elicit reflex contraction of the gall-bladder (in anaesthetized
animals) in this way.
/ NFL UENCE OF NER VO US S YSTEM ON DIGESTI VE GLA NDS 413
a solution of the residue containing the secretin still evokes a rapid
secretion of bile. The fact that the same hormone excites the
formation both of pancreatic juice and bile is obviously related to
that common action of the two juices in digestion on which we have
already dwelt.
When food passes into the stomach, there is at once a sharp rise in
the rate of secretion of bile. A maximum is reached from the fourth
to the eighth hour — that is, while the food is in the intestine. There
is then a fall, succeeded by a second smaller rise about the fifteenth
or sixteenth hour, from which the secretion gradually declines to its
minimum. Upon the whole, the curves of secretion of pancreatic
juice and bile show a fairly close correspondence, except that the
latter is more nearly continuous. But when we compare the curves
representing the rate at which the bile actually enters the intestine
with the curve of pancreatic secre-
tion (Fig. 169), we are struck by
their almost absolute parallelism.
This lends additional support to
the conclusion deduced from their
chemical and physical properties,
that in digestion they are partners
in a common work.
While the rate at which bile
passes into the intestine seems to be
influenced by digestion much in the
Same way as the rate Of pancreatic sent the hourly rate of pancreatic
Secretion, the details are as yet less secretion, and the lower the rate at
pvartlv krmwn Tn thp fasting which the bile enters the intestine ;
,tiy Known. „„& *. «'. milk diet; b, b', meat; c, c',
animal no bile enters the gut. When bread. Only the general form of
food is taken, the flow begins after the curves is to be compared. The
a definite interval, which varies for scale of the ordi nates of the various
,, , , curves was not the same.
the different kinds of food. As
long as digestion lasts bile continues to escape, but both the
quantity and quality depend upon the nature of the food. Water,
raw egg-white, and starch paste, whether given by the mouth or
introduced directly into the stomach of a dog, cause no flow of bile.
But fat, the extractives of meat, and the products of digestion of
egg-white produce a copious discharge. This discharge may be
determined by the relatively large amount of acid chyme passed
through the pylorus when proteins are digested in the stomach and
the stimulus to the formation of secretin occasioned by the presence
of this chyme or of fatty material in the duodenum. In the case of
fat a further favourable influence on the secretion of bile is the
absorption of bile-salts which accompanies the absorption of the
fatty acids and soaps produced in fat digestion. Bile-salts stimulate
the secretion of bile, including bile-salts themselves. An increased
4*4 DIGESTION
flow of bile-salts into the intestine accelerates the splitting of fats by
the pancreatic juice, and therefore the absorption of bile- salts acting
as solvents for, or chemically united to, the fatty acids and soaps.
A circle analogous to the ' vicious circle ' of the logicians, but con-
stituting a physiological adaptation of most potent virtue in the
digestion of fats, is thus established. Not only is the quantity of
bile poured into the intestine increased on a diet rich in fat, but it
is said that a given amount of it aids the fat-splitting action of the
pancreatic juice more powerfully than if the diet were poor in fat.
This may depend upon an increase in the concentration of the bile-
salts in bile secreted when a large amount of fat is ingested. But it
is well to recognize that we do not at present know with any great
exactness the mechanism by which the rate of secretion and ex-
pulsion of bile and the properties of that juice are influenced by
digestion. It has been conjectured that the first abrupt rise may be
started by reflex nervous action, and that later on secretin and, in the
case of fat digestion, bile-salts may directly excite the hepatic cells.
The pressure under which the bile is secreted is higher than the
pressure of the portal blood, and therefore the liver ranges itself with
the high-pressure salivary glands rather than with the low-pressure
pancreas. But although the biliary pressure is high relatively to
that of the blood with which the secreting cells are supplied, it is
absolutely low, the maximum being no more than 25 mm. of mer-
cury.* This is a point of practical importance, for a comparatively
slight obstruction to the outflow, even such as is offered by a con-
gested or inflamed condition of the duodenal wall about the mouth
of the duct, may be sufficient to cause reabsorption of the bile
through the lymphatics, and consequent jaundice. Of course,
complete plugging of the duct by a biliary calculus is a much more
formidable barrier, and inevitably leads to jaundice, just as ligature
of a salivary duct, in spite of the great secretory pressure, inevitably
causes oedema of the gland.
The Influence of Nerves on the Secretion of Intestinal Juice. — As
to the influence of nerves on the secretion of the succus entericus, our
knowledge is almost limited to a single experiment, and that an in-
conclusive one. Moreau placed four ligatures on a portion of the
small intestine, so as to form three compartments separated from
each other and from the rest of the gut. The mesenteric nerves
going to the middle loop were divided, and the intestine returned to
the abdomen. After some time a watery secretion was found in the
middle compartment, little or none in the others. This is a true
' paralytic ' secretion, and not a mere transudation depending
simply on the vascular dilatation caused by section of the vaso-
* In the dog, cat, and monkey the average maximum pressure at which
as much bile is secreted as is taken up from the bile-paths by the portal
lymphatics is about 300 mm. of bile. The highest pressure recorded was
373 mm. of bile in a cat (Herring and Simpson).
INFLUENCE OF NERVOUS SYSTEM ON DIGESTIVE GLANDS 415
constrictor nerves, for it has the same composition and digestive
action as normal succus entericus obtained from a fistula. The
secretion begins about four hours after section of the nerves, goes on
increasing for about twelve hours, and then rapidly diminishes, so
that after about two days the middle loop, as well as the other
two, will be found empty. The interpretation usually put upon the
experiment is that nerves which normally inhibit the local secre-
tory mechanism have been divided. But there is no real proof of
the existence of such nerves.
The same adaptation is seen in the secretion of the succus entericus
as in the secretion of the other digestive juices, and the adaptation
is naturally most striking in regard to those points in which the
intestinal juice is peculiar. While mechanical stimulation of the
stomach is ineffective as regards the secretion of gastric juice,
mechanical stimulation of the intestine, as by the contact of a
cannula, produces a free flow of succus entericus. The reaction is a
localized one, the secretion only taking place from the portion of the
mucous membrane stimulated. This fact acquires significance when
we reflect that the food moves very slowly in the intestine, and a
secretion could be of use only at the points where the food happened
to be. The juice secreted in response to mechanical stimulation is
poor in enterokinase. But if a little pancreatic juice be put into the
intestine, and left there for some time, the juice afterwards secreted
is rich in enterokinase.
Summary. — Here let us sum up the most important points relat-
ing to the secretion of the digestive juices. They are all formed' by
the activity of gland-cells originally derived from the epithelial lining
of the alimentary canal. The organic constituents or their precursors
(including the mother-substances of the ferments) are prepared in the
intervals of rest — absolute in some glands, relative in others — and
stored up in the form of granules, which during activity are moved
towards the lumen of the gland tubules, and there discharged.
The nerves of the salivary glands are, as regards their origin, (a)
cerebral, (b) sympathetic ; the former group is vaso-dilator, the latter
(usually] vaso-constrictor ; both are secretory. Secretion of saliva
depends strictly on the nervous system. That nerves influence the
gastric and pancreatic secretions is also made out. The psychical secre-
tion is of greater importance for the saliva and gastric juice than for
the pancreatic juice. The direct action of secretin (produced in the
intestinal mucous membrane by the influence of the chyme) is the most
characteristic factor in pancreatic secretion. As regards the intestinal
glands and the liver, it has not been proved that their secretive activity
is under the control of the nervous system, except in so far as the latter
may indirectly govern it through the blood-supply, although various
circumstances suggest the probability of a more direct action. All the
digestive juices show a certain adaptation to the nature of the food,
4i 6 DIGESTION
although it has not been demonstrated that this is due to a specific sensi-
bility of the mucous membranes for each kind of food-stuff. The
action of one juice on the secretion of another is also of great significance.
Thus, the water of the saliva directly excites a flow of gastric juice when
it reaches the stomach ; the acid of the gastric juice excites a fiow of
Pancreatic juice when it reaches the duodenum; and the pancreatic
juice excites the intestinal mucous membrane to the production of
enter okinase, the most characteristic constituent of the succus entericus.
In all the glands the blood-flow is increased during activity ; in some
(salivary glands) this is known to be caused through vaso-motor nerves.
In the salivary glands electro-motive changes accompany the active
state, and more heat is produced. Both in the salivary glands and the
Pancreas it has been shown that much more carbon dioxide is given off,
and much more oxygen used up, during secretion than during rest. In
the other glands we may assume that the same occurs. This is one
proof that work is done in the separation or manufacture of the con-
stituents of the various secretions.
SECTION VI. — SURVEY OF DIGESTION AS A WHOLE.
Having discussed in detail the separate action of the digestive
secretions, it is now time to consider the act of digestion as a whole,
the various stages in which are co-ordinated for a common end.
The solid food is more or less broken up in the mouth and mixed
with the saliva, which its presence causes to be secreted in consider-
able quantity. Liquids and small solid morsels are shot down the
open gullet without contraction of the constrictors of the pharynx,
and reach the lower portion of the oesophagus in a comparatively
short time (fa second); while a good-sized bolus is grasped by the
constrictors, then by the oesophageal walls, and passed along by a
more deliberate peristaltic contraction.
Chemical digestion in man begins already in the mouth, a part of
the starch being there converted into dextrins and sugar (maltose),
as has been shown by examining a mass of food containing starch
just as it is ready for swallowing (p. 456). This process is no doubt
continued during the passage of the food along the oesophagus.
The first morsels of a meal which reach the stomach find it free
from gastric juice, or nearly so. They are alkaline from the ad-
mixture of saliva ; and the juice which is now beginning to be secreted,
in response to the psychical excitement, and reflexly through the
presence of the food and the water of the saliva in the stomach, is for
a time neutralized, and amylolytic digestion still permitted to go on.
For 20 to 40 minutes after digestion has begun there is no free
hydrochloric acid in the stomach, although some is combined with
proteins, and during this period the ptyalin of the swallowed saliva
will be able to act even better than in the mouth, being favoured by
SURVEY OF DIGESTION AS A WHOLE 417
a weakly acid reaction. Indeed, for a time, as the meal goes on, the
successive portions of food which arrive in the stomach will find the
conditions more and more favourable for amylolytic digestion. But
as the acidity continues to increase, the activity of the ptyalin will
first be lessened, and ultimately abolished; and, upon the whole, a
considerable proportion of the starches must usually escape com-
plete conversion into sugar until they are acted upon by the pan-
creatic juice. This is particularly the case with unboiled starch, as
contained in vegetables which are eaten raw ; and, indeed, we know
that sometimes a certain amount of starch may escape even pan-
creatic digestion, and appear in the faeces. Meanwhile, pepsin and
hydrochloric acid are being poured forth; the latter is entering into
combination with the proteins of the food ; and before the end of an
ordinary meal peptic digestion is in full swing. The movements of
the pyloric end of the stomach increase, and eddies are set up in its
contents, which carry the morsels of food with them, and throw them
against its walls. In this way not only are the contents thoroughly
mixed, and fresh portions of food constantly brought into contact
with the gastric juice secreted mainly in the more passive cardiac
end, but a certain amount of mechanical disintegration is brought
about. This is aided by the digestion of the gelatin-yielding con-
nective tissue which holds together the fibres of muscle and the cells
of fat, and the digestible structures in vegetable tissue which enclose
starch granules. Such nucleo-proteins as come into contact with the
gastric juice will be split up and the proteins digested to peptone.
The globin of the blood pigment will undergo the same change, while
the haematin is not much affected. If milk has formed a portion of
the meal, the caseinogen will have been curdled soon after its
entrance into the stomach, by the action of the rennet ferment alone
(see p. 353) when the milk has been taken at the beginning of
digestion before the gastric contents have become distinctly acid, by
the acid and ferment together when it has been taken later. The
caseinogen and other proteins of milk, like the myosinogen and other
proteins of meat, and the globulins, albumins, and other proteins of
bread and of vegetable food in general, are acted upon by the pepsin
and hydrochloric acid, yielding ultimately peptones; while variable
quantities of these proteins and of the acid-albumin and proteoses
derived from them may escape this final change, and pass on as such
into the duodenum. In the dog, indeed, a very large proportion of
a meal of flesh has been found to be digested to the peptone stage
while still in the stomach, leaving for the juices that act on it in the
intestine only its further hydrolysis to amino-acids, etc. But we
may safely assume that, in the case of a man living on an ordinary
mixed diet, a good deal of the food proteins passes through the
pylorus chemically unchanged, or having undergone only the first
steps of hydration. For, even a few minutes after food has been
•27
418 DIGESTION
swallowed, especially liquid food or water, the pyloric sphincter
may relax and allow the stomach to propel a portion of its contents
into the intestine; and such relaxations occur at intervals as diges-
tion goes on, although it is not for several hours (three to five) that
the greater portion of the food reaches the duodenum. During this
period the acidity has at first been constantly increasing, although
for a time the hydrochloric acid has combined, as. it is formed, with
the proteins of the food. Then comes a stage where the hydrochloric
acid has so much increased that, after combining with all the proteins,
some of it remains over as free acid. After a time the total acidity
begins to fall, the partially digested proteins continually passing on
through the pylorus, while a considerable proportion is so fully
digested as to be absorbed by the gastric mucous membrane itself.
Thus, in one experiment on the digestion of meat in a dog, it was
found that 30 per cent, was absorbed in the stomach, while 40 per
cent, passed through the pylorus as peptone, over 20 per cent, as
undissolved or soluble protein (acid-albumin), and a little more than
8 per cent, as proteose (Tobler). The large proportion of peptone
is noteworthy, as indicating some kind of selective passage of the
different digestive products from the stomach into the duodenum.
For the gastric contents contain plenty of proteose, although only
traces of peptone. The total ' titratable acidity ' goes on diminishing
till the third or fourth hour, the proportion of free to combined acid
continuing, nevertheless, to rise, since nearly all that is now secreted
remains free. In addition to a certain amount of protein, small
quantities of soluble and easily diffusible substances, like sugars and
some of the organic crystalline constituents of meat — e.g., kreatin —
may also be absorbed into the blood by the gastric mucous membrane.
The substances which reach the duodenum are — (i) The greater
part of the fats. The partial digestion in the stomach of the enve-
lopes and protoplasm of the cells of adipose tissue, and of the protein
which keeps the fat of milk in emulsion, prepares the fats which are
not split up by the gastric juice for what is to follow in the intestine.
(2) All the proteins which have not been carried to the stage of
peptone, and much peptone. (3) All the starch and dextrins — and
glycogen, if any be present — which have not been converted into
sugars, and probably a portion of the sugars. (4) Nucleins, haematin,
cellulose, and other substances not digestible, or digestible only with
difficulty, in gastric juice. (5) The constituents of the gastric juice
itself, including pepsin. Most of the pepsin is soon destroyed in the
unfavourable environment of the intestinal contents. But it has
been shown that a certain amount of active pepsin may be present
for a rime in the intestine, even in the free condition, and still more
when enclosed in the interior of masses of protein which protect it,
and which still continue to be digested by it. This is particularly
true of certain materials, like elastin and connective tissue, which are
SURVEY OF DIGESTION AS A WHOLE 419
more readily hydrolysed by pepsin than by trypsin. The ptyalin
of the saliva has been already destroyed in the stomach.
It must be remembered that all this time, even from the beginning
of digestion, a certain amount of pancreatic juice has been finding
its way into the duodenum in response first perhaps to the psychical
excitation, and later to that action of the acid chyme on the in-
testinal mucous membrane which has been described. In the
duodenum its trypsinogen is becoming activated to trypsin by the
enterokinase of the intestinal juice. The secretion of bile, too, has
quickened its pace, the gall-bladder is getting more and more full as
the meal proceeds and gastric digestion begins, and some of the bile
may very soon escape into the intestine. The pylorus opens occa-
sionally for a moment whenever the small portions of chyme which
at this stage are beginning to pass through have been sufficiently
neutralized by the pancreatic juice and bile, although it is not
necessary that the reaction should become actually neutral. When
the acid chyme, a greyish liquid, turbid with the debris of animal and
vegetable tissues— with muscular fibres, fat globules, starch granules,
and dotted ducts — gushes through the pylorus and strikes the
duodenal wall, the muscular fibres of the gall-bladder contract, and
sudden rushes of bile take place from the common duct. By-and-by
as bile and pancreatic juice continue to be poured out, the reaction
in the duodenum becomes less acid and even weakly alkaline.
The observations purporting to show changes in reaction of the
intestinal contents at different levels made with indicators like
litmus, phenolphthalein, methyl orange, etc., have lost much of
their value since the introduction of physico-chemical methods for
measuring the hydrogen-ion concentration. However, properly
chosen colour indicators can still be employed for estimating the
acidity of the gastric contents, at least with sufficient accuracy for
most clinical purposes. It must be remembered that the differ-
ences in true reaction at different stages of intestinal digestion and
at different levels of the gut below the duodenum are slight. There
is never a great preponderance either of hydroxyl or of hydrogen
ions between the point at which the pancreatic juice and bile are
mingled with the gastric chyme and the lower part of the ileum.
In the duodenal contents of adult human beings a hydrogen-ion con-
centration of 0-00000002 (or ax icrs) normal has been found by the
gas chain method (McClendon) and about the same in the intestinal
contents of dogs (Auerbach and Pick). This is a slightly alkaline
reaction, the hydrogen-ion concentration of pure water being about
five times as great (O-ooooooi, or i x 10-7). In the stomach, of course,
a very different state of affairs is found. The hydrogen-ion concen-
tration rises in the course of i to 3 or 4 hours after a meal to a maxi-
mum which is very considerable. In a series of patients, including a
number suffering from gastric disorders, the hydrogen-ion concentra-
tion ranged from 0*03 to 0-00000007 (or jx io-s). The lowest concen-
420 DIGESTION
tration is practically the same as that of water. In other words, in
this patient the gastric contents after the test meal were neutral, and
it would be impossible for peptic digestion to. proceed. It must be
distinctly noted that the acidity of the gastric contents during the
digestion of test meals is not the same thing as the acidity of the pure
gastric juice. Observations on juice obtained from a case of gastric
fistula without admixture with saliva showed that in ' hunger ' juice,
where continuous secretion was going on, the hydrogen-ion concentra-
tion varied from 0-056 to o-ioo normal in several samples collected on
different days (Menten).
This question of reaction has significance in two ways : in the first
place the reaction determines whether a given ferment shall be
destroyed or not by another ferment or by the alkalinity or acidity
of the medium. Thus pepsin can be destroyed by the alkali of the
pancreatic juice, enterokinase and trypsin by the hydrochloric acid
of the gastric juice, trypsinogen by the pepsin and hydrochloric
acid. Trypsin has no destructive effect on enterokinase or tryp-
sinogen (Mellanby). Secondly, the reaction affects the activity of
this or that ferment on the food substances. The optimum hydro-
gen-ion concentration for peptic digestion is relatively high (0-02
to 0-03 normal). When it is decreased to o«oooi normal the rate
of digestion is only one-half to one-fifth as rapid. The high con-
centration of hydrogen-ions in the gastric contents of healthy persons
is clearly advantageous, and the low concentration in the gastric
contents in cases of hypoacidity clearly disadvantageous. Trypsin
acts best in a medium which contains more hydroxyl than hydrogen
ions. When the alkalinity is diminished it becomes less active,
although it is not entirely inhibited even by an acid reaction until
the hydrogen-ion concentration reaches about o-oooi (or IXIQ-*)
normal. (See footnote, p. 1139.)
In the intestine it is possible that trypsin may perform its work
in a medium which is sometimes acid; and although the cause of
the acidity and the character of the medium are far from being the
same as in the gastric juice, it is obviously an advantage that the
chief proteolytic ferment should be able to act upon the proteins in
all parts of the intestine and at every stage of intestinal digestion
whether the reaction is acid or alkaline. The proteins of the chyme
are all carried by the trypsin to the stage of peptone, and the pep-
tone, even in perfectly normal digestion, is further split up into
amino- and diamino-acids by the trypsin and by the erepsin of the
succus entericus.
In the lower portions of the small intestine bacteria of various
kinds are present and active; and it is not unlikely that even
throughout its whole length a certain range of action is permitted
to them, checked by the acidity of the chyme, though scarcely by
the feeble antiseptic properties of the bile.
The lower end of the small intestine is not cut off by any bacteria-
proof barrier from the large intestine, in which putrefaction is con-
SURVEY OF DIGESTION AS A WHOLE 421
stantly going on. It has been actually shown that small particles,
such as lycopodium spores, suspended in water, soon reach the
stomach when injected into the rectum. So that micro-organisms,
aided by the antiperistalsis of the colon, may be able to work their
way above the ileo-colic sphincter and valve, even against the
downward peristaltic movement of the small intestine. But even if
this were not the case, a few bacteria or their spores, passing through
the stomach with the food, would be enough to set up extensive
changes as soon as they reached a part of the alimentary canal
where the conditions were favourable to their development. In-
deed, from the time when the first micro-organism enters the diges-
tive tube soon after birth, it is never free from bacteria; and their
multiplication in one part of it rather than another depends not so
much on the number originally present to start the process, as on
the conditions which encourage or restrain their increase.
A certain amount of already emulsified fats is broken up into
their fatty acids and glycerin in the stomach, unemulsified fats
entirely by the fat-splitting ferment of the pancreatic juice. The
acids will form soaps with alkalies wherever they meet them in the
intestinal contents, or even in the mucous membrane. A portion
of those soluble soaps may be immediately absorbed; the rest will
aid in the emulsification of the fats not yet chemically decomposed,
and thus greatly hasten the fat -splitting action of the pancreatic
juice. The phosphatides are in all probability acted upon in the
alimentary canal much in the same way as the fats. Lecithin is
decomposed by pancreatic and intestinal juice into fatty acids and
glyceryl-phosphoric acid, and cholin is liberated. As regards the
behaviour of the sterins of the food little is known, but it is not
unlikely that their esters are split up, and the sterins thus set free
as well as those originally free in the food may then be absorbed,
in part at least, without further change. The starch and dextrin
which have escaped the action of the saliva are changed into
maltose by the amylase of the pancreatic juice, and the maltose
into dextrose by the maltase of the same secretion and of the succus
entericus.
The succus entericus, in addition to its important functions
already mentioned, aids as an alkaline liquid in lessening the acidity
of the chyme and establishing the reaction favourable to intestinal
digestion. It will convert into monosaccharides any cane-sugar,
maltose, or lactose, which may reach the intestine; but it cannot
be doubted that some cane-sugar may be absorbed by the stomach,
after being inverted by the hydrochloric acid of the gastric juice
or by inverting ferments taken in with the food, or on its way
through the gastric walls.
Upon the whole no great amount oi water is absorbed in the small
intestine, or at least the loss is balanced by the gain, for the intestinal
422 DIGESTION
contents are as concentrated in the doudenum as in the ileum. But
as soon as they pass beyond the ileo-caecal valve water is rapidly
absorbed, and the contents thicken into normal faeces, to which the
chief contribution of the large intestine is mucin, secreted by the
vast number of goblet cells in its Lieberkiihn's crypts.
Bacterial Digestion. — So far we have paid no special attention to
other than the soluble ferments of the digestive tract, although
we have incidentally mentioned the action of the lactic acid bacilli
on carbo-hydrates and of the fat-splitting bacteria on fats. It is
now necessary to recognize that the presence of bacteria is an
absolutely constant feature of digestion; and although their action
must in part be looked upon as a necessary evil which the organism
has to endure, against the consequences of which it has to struggle,
and to which in all probability it has to a great extent adapted
itself, it is not unlikely that in part it may be ancillary to the pro-
cesses of aseptic digestion. But bacteria are not essential (in mam-
mals, at any rate, living on milk), as some have supposed. For it
has been shown that a young guinea-pig, taken by Caesarean section
from its mother's uterus with elaborate aseptic precautions, and
fed in an aseptic space on sterile milk, grew apparently as fast as one
of its sisters brought up in the orthodox microbic way. The ali-
mentary canal remained free from bacteria (Nuttall and Thierfelder).
On the other hand, chickens hatched from sterile eggs and kept in
a sterile enclosure lived, indeed, for a time, but did not thrive in
comparison with the control animals, and died at latest after eighteen
days (Schottelius) . It is probable that the difference in the results
is to be attributed to the difference in the food, purely vegetable
food requiring the aid of bacteria for its proper digestion, especially
for the decomposition of the cellulose, while an easily-digestible
food like milk does not.
Among the more important actions of bacteria on the protein
food-products in the intestines may be mentioned the formation
of indol, phenol, and skatol, the first having tyrosin for its precursor,
and being itself after absorption the precursor of the indican in the
urine; the second being to a small extent thrown out with the faeces,
but chiefly absorbed and eliminated by the kidneys as an aromatic
compound of sulphuric acid; the third passing out mainly in the
faeces.
The view put forward by Metchmkoff, that in the putrefactive
bacteria of the intestine the body carries within itself the seeds of
premature decay, owing to the harmful effects of absorbed products
of decomposed protein, cannot be looked upon as established,
although certainly the prophylaxis suggested by him (the increase
of the lactic acid content of the intestine by the addition of sour
milk, butter-milk, etc., to the diet) might well be a useful modifica-
tion of the dietetic habits of many persons, especially if associated
SURVEY OF DIGESTION AS A WHOLE 423
with a reduction in the total amount of protein consumed. That
the intestinal contents may include substances capable of inducing
severe toxic symptoms if absorbed unchanged scarcely needs proof.
Filtered extracts of faeces from normal persons made with salt
solution cause, when injected in small amounts into the circulation
of dogs, a fall of blood-pressure which may be speedily recovered
from or may be quickly fatal according to the specimen (Fig. 170).
The large intestine is the chosen haunt of the bacteria of the
alimentary canal; they swarm in the faeces, and by their influence,
especially in the caecum of herbivora, but also to some extent in
man, even cellulose is broken up, the final products comprising
certain fatty acids, such as butyric, acetic and valerianic acids,
carbon dioxide and marsh gas. A cellulose-dissolving enzyme of
great activity is present in the hepatic secretion of the snail, which
rapidly produces sugar from that polysaccharide. Dextrose is also
formed when it is hydrolysed by dilute acid. Apart from the im-
portance of solution of the cellulose in facilitating the action of the
digestive juices on the starch and other nutrient materials enclosed
by it, it can be assumed that some of the intermediate products of
its hydrolysis by the bacteria — e.g., bodies analogous to the dex-
trins which appear in the hydrolysis of starch — can be acted on by
the ferments of the succus entericus and the pancreatic juice, so
as to form dextrose, which on absorption then takes its place in
the carbo-hydrate metabolism just as if it had been derived from
starch. In the herbivora the contribution thus made to the nutri-
tion of the animal may be of considerable importance; in omnivora
it is not negligible. In man as much as 40 per cent, of the cellulose
of young vegetables is said to be capable of assimilation. In car-
nivorous animals, however, it appears that cellulose when taken in
the food is quantitatively excreted in the faeces. In addition to
the action of the intestinal flora on cellulose, certain of the bacteria
of the alimentary canal affect some of the other carbo-hydrates in a
not unimportant way. Dextrose, for instance, can be decomposed
into two molecules of lactic acid, according to the equation
C6H12O6 = 2C3H6O3.
This is called the lactic acid fermentation, and is due to a special
bacillus.
Another micro-organism splits up dextrose into butyric acid,
carbon dioxide and hydrogen, the so-called butyric acid fermenta-
tion, according to the equation
C6H12O6 - C4H8O2 + 2CO2 + 2H2.
The contents of the large bowel are generally acid from the
products of bacterial action, although the wall itself is alkaline.
Faeces. — In. addition to mucin, secreted mainly by the large
424 DIGESTION
intestine, the faeces consist of indigestible remnants of the food, such
as elastic fibres, spiral vessels of plants, and in general all vegetable
structures chiefly composed of cellulose. They are coloured wich a
pigment, stercobilin, derived from the bile -pigments. Stercobilin
is identical with urobilin, which forms a common, though not an
Fig. 170.— Effect of Extract of Faeces on Blood-Pressure. The extract was injected
at 2. Time-trace, seconds.
invariable, constituent of bile itself. A portion of it is absorbed by
the intestine and then excreted in the urine, the urobilin in which
is often much increased in fever (' febrile ' urobilin). No bilirubin
or biliverdin occurs in normal faeces, although pathologically they
may be present. The dark colour of the faeces with a meat diet is
due to haematin and sulphide of iron, the latter being formed by
the action of the sulphuretted hydrogen which is constantly present
in the large intestine on the organic compounds of iron contained in
the food or in the secretions of the alimentary canal. A small
amount of altered bile-acids and their products is also found; and
in respect to these, and to the altered pigments, bile is an excretion.
And although its entrance into the upper instead of the lower end
of the intestine, the ascertained importance of its function in diges-
tion, and the fact that the greater part of the bile-salts is reabsorbed,
show that in the adult it is very far from being solely a waste product,
the equally cogent fact, that the intestine of the new-born child
is filled with what is practically concentrated bile (meconium),
proves that it is just as far from being purely a digestive juice.
Skatol and other bodies, formed by putrefactive changes in the
proteins of the food, are also present in the faeces, and are responsible
for the faecal odour. Masses of bacteria are invariably present, and
often make up a very considerable proportion of the total faecal
SURVEY OF DIGESTION AS A WHOLE 425
solids. Of the inorganic substances in faeces the numerous crystals
ot triple phosphate are the most characteristic. When the diet is
too large, or contains too much of a particular kind of food, a con-
siderable quantity of digestible material may be found in the fasces —
e.g., muscular fibres and fat. But it should be remembered that
under all circumstances the composition of the faeces differs from
that of the food. The intestinal contribution is always an important
one, although relatively more important with a flesh than with a
vegetable diet. The purin bases normally found in human faeces
come both from the food directly and from the metabolism of
the tissues. They are increased in amount on a diet rich in
purin bodies (such as meat extract or thymus), but are also formed
on a diet like milk, from which purin bases cannot be obtained.
An interesting constituent of faeces on which light has recently been
thrown, especially by the researches of Gardner, is the so-called copro-
sterin (dihydrocholesterin), which appears to be produced from
cholesterin by reduction, probably under the influence of bacteria,
and perhaps also from the phytosterins of vegetable food.
CHAPTER VII
ABSORPTION
SECTION I. — PRELIMINARY PHYSICO-CHEMICAL DATA.
Imbibition, or molecular imbibition, is the term applied to the en-
trance of liquid into a colloid, without the loss of its properties as a solid,
when no preformed capillary spaces are present. The entrance of water
into a piece of gelatin, or an epidermic scale, is an example of molecular
imbibition. Most animal and vegetable tissues possess this property,
which is believed to be of importance in such physiological processes as
absorption, secretion, and the excretion of water from the lungs and
skin. The process by which liquid passes into a solid with preformed
capillary spaces — e.g., a sponge — is sometimes spoken of as capillary
imbibition.
Diffusion. — When a solution of a substance is placed in a vessel, and
a layer of water carefully run in on the top of it, it is found after a time
that the dissolved substance has spread itself through the water, and
that the composition of the mixture is uniform throughout. The
result is the same when two solutions containing different proportions
of the same substance, or containing different substances, are placed in
contact. The phenomenon is called diffusion. The time required for
complete diffusion is comparatively short in the case of a substance like
hydrochloric acid or sodium chloride, exceedingly long in the case of
albumin or gum. In both it is more rapid at a high temperature than
at a low.
Osmosis. — If the solution be separated from water by a membrane
absolutely or relatively impermeable to the dissolved substance, but
permeable to water, water passes through the membrane into the solu-
tion. This phenomenon is called osmosis. E.g., a membrane of ferro-
cyanide of copper, nearly impermeable to cane-sugar, can be formed
in the pores of an unglazed porcelain pot by allowing potassium ferro-
cyanide and cupric sulphate to come in contact there. If the pot is
filled with, say, a i per cent, solution of cane-sugar, closed by a suitable
stopper, connected to a manometer, and then placed in a vessel of water,
water passes into it till the pressure indicated by the manometer rises
to a certain height. With a 2 per cent, solution it reaches twice this
height, and in general the osmotic pressure, as it is called, is in an}'
solution proportional to the molecular concentration* of the solution,
* The molecular concentration is strictly denned as the number of
grammes of the dissolved substance in a litre of the solution divided by the
gramme-molecular weight. The gramme-molecular weight, or gramme
molecule, is the number of grammes corresponding to the molecular weight.
Thus, the gramme-molecular weight of sodium chloride (NaCl) is 58*36
grammes, and of cane-sugar (CjsH^Ojj), 342 grammes.
426
PRELIMINARY PHYSICO-CHEMICAL DATA
427
JO.
or, in other words, to the number of molecules of the dissolved substance
in a given volume of the solution. If in this sentence we substitute
' gaseous pressure ' for ' osmotic pressure,' and ' gas ' for ' solution,'
we have a statement of Boyle's law, which asserts that the pressure of a
gas is proportional to its density. Indeed, it has been shown that the
osmotic pressure of the dissolved substance is the same as the pressure
that would be exerted by a gas, say hydrogen, if all the water were
removed, and a molecule of hydrogen substituted for each molecule of
the substance, or as would be exerted by the substance itself if, after
removal of the solvent, it could be left as a gas filling the
same volume. And the osmotic pressure of a solution of
one substance is the same as that of a solution of any
other substance which contains in a given volume the
samo number of molecules of the dissolved substance.
In other words, the osmotic pressure is not dependent on
the nature, but on the molecular concentration, of the
substance. The analogy of the laws of osmotic to those
of gaseous pressure becomes still more obvious when
it is added that the osmotic pressure of a substance with
any given molecular concentration is proportional to the
absolute temperature ; and that when a solution contains
more than one dissolved substance the total osmotic pres-
sure is the sum of the partial osmotic pressures
which each substance would exert if it were
present alone in the same volume of the solution.
The osmotic pressure of a solution may reach
an enormous amount. Thus, a i per cent, solu-
tion of cane-sugar has a pressure at o° C. of
493 mm. of mercury. A 10 per cent, solution
of cane-sugar would have an osmotic pressure of
more than six atmospheres, and a 17 per cent,
solution of ammonia a pressure of no less than
224 atmospheres. The manner in which the
phenomenon known as osmotic pressure is de-
veloped is not definitely known. One -Cheory
attributes it to the attraction between the
dissolved molecules and the molecules of the
solvent on the other side of the membrane.
The most commonly accepted view is that the
osmotic pressure is due to the kinetic energy
of the moving molecules. Where the mole-
cules are hindered from passing a bounding
membrane, the pressure excited by their im-
pacts on the boundary is greater than where
the membrane is easily permeable, because in
the latter case many of the molecules pass
through, carrying with them their kinetic
energy. The pressure must be still less when
a dissolved substance diffuses freely into water ;
but however small it may become, it is in the same force which gives
rise to the osmotic pressure of the molecules of the dissolved substance
that the cause of diffusion must be sought. Recently interest in the
nature of the membrane itself as an important factor in osmosis has been
revived (Kahlenberg, Armstrong, etc.). There are many facts which
indicate that in physiological processes the affinity of the dissolved sub-
stances for, or their solubility in, the cell envelopes or the cytoplasm
plays an important role.
Fig. 171. — Beckmann's
Apparatus. For de-
scription, see p. sac.
428 ABSORPTION
It is as yet impossible or at least very difficult to directly measure
the osmotic pressure with accuracy by means of a semi-permeable mem-
brane. Recourse is therefore had to indirect methods, especially one
which depends on the fact that the freezing-point of a solution is lower
than that of the solvent, salt water, e.g., freezing at a lower temperature
than fresh water. The amount by which the freezing-point is lowered
depends on the molecular concentration of the dissolved substance, to
which, as we have seen, the osmotic pressure is also proportional. When
a gramme-molecule of a substance is dissolved in water, and the volume
made up to a litre, the freezing-point is lowered by r86° C. ; the osmotic
pressure is 22-35 atmospheres (16,986 mm. of mercury). It is therefore
easy to calculate the osmotic pressure of any solution if we know the
amount by which its freezing-point is lowered. A i per cent, solution of
cane-sugar, for example, would freeze at about — 0-054° C. Its osmotic
pressure = —,^x 16,986=493 mm. of mercury.
A convenient apparatus for making freezing-point measurements is
shown in Fig. 171. The details of the method are given in the Practical
Exercises, p. 529.
The osmotic pressure of different solutions may also be compared
by observing the effect produced on certain vegetable and animal cells.
When a solution with a greater osmotic pressure than the cell-sap (a
hyperisotonic solution) is left for a time in contact with certain cells in
the leaf of Tradescantia discolor, plasmolysis occurs — that is, the proto-
plasm loses water and shrinks away from the cell-wall. If the osmotic
pressure of the solution is lower than that of the coloured cell-sap
(hypoisotonic solution), no shrinking of the protoplasm takes place. By
using a number of solutions of the same substance but of different
strength, two can be found, the stronger of which causes plasmolysis,
and the weaker not. Between these lies the solution which is isotonic
with the cell-sap — that is, has the same molecular concentration and
osmotic pressure. The strength of an isotonic solution of some other
substance can then be determined in the same way with sections from
the same leaf.
Animal cells (red blood-corpuscles) may also be employed, the libera-
tion of haemoglobin or the swelling of the corpuscles, as measured by
the haematocrite (p. 27), being taken as evidence that the solution in
contact with them is hypoisotonic to the contents of the corpuscles.
Here we may suppose that the impacts of the molecules of the salts of
the corpuscle on the inside of its envelope, not being balanced by
similar impacts on the outside, tend to distend it, and thus to create a
potential vacuum for the surrounding water, which accordingly enters.
If the corpuscles shrink, the solution is hyperisotonic to their contents.
But since the cells are much more permeable to certain substances than
to others, this method does not always yield trustworthy results.
Electrolytes. — We have said that the osmotic pressure is proportional
to the concentration of the solution, but this statement must now be
qualified. For certain compounds, including all inorganic salts and
many organic substances, the osmotic pressure decreases less rapidly
than the theoretical molecular concentration as the solution is diluted.
The explanation is that in solution some of the molecules of these bodies
are broken up into simpler groups or single atoms, called ions. Each
ion exerts the same osmotic pressure as the molecule did before. The
proportion between the average number of these dissociated molecules
and of ordinary molecules is constant for a given concentration of the
solution and a given temperature. But as the solution is diluted, the
proportion of dissociated molecules becomes greater. The bodies which
PRELIMINARY PHYSICO-CHEMICAL DATA 429
behave in this way are electrolytes — that is, their solutions conduct a
current of electricity; bodies which do not exhibit this behaviour do
not conduct in solution. And there are many reasons for believing
that the dissociation of the electrolytes is the essential thing in elec-
trolytic conduction. We may suppose that in a solution of an electro-
lyte— sodium chloride, for instance — a certain number of the molecules
fall asunder into a kation (Na+),* carrying a charge of positive elec-
tricity, and an anion (Cl— ), carrying an equal negative charge. These
electrical charges, it must be remembered, are not created by the
passage of a current through the solution. We do not know how they
arise, but the ions must be supposed to be electrically charged at the
moment when the molecule is broken up. And the ions of different sub-
stances must each be supposed to carry the same quantity of electricity.
But since they are all wandering freely in the solution, no excess of
negative or of positive electricity can accumulate at any part of it — in
other words, no difference of potential can exist. When electrodes
connected with a voltaic battery are dipped into a solution of an elec-
trolyte, a difference of potential, an electrical slope, is established in the
liquid, and the positively charged kations are compelled to wander
towards the negative pole, the negatively charged anions towards the
positive pole. In this way that movement of electricity which is called
a current is maintained in the solution. It is clear that the greater
the number of ions, and the faster they move in the solution, the greater
will be the quantity of electricity carried to the electrodes in a given
time, when the difference of potential between the electrodes, or the
steepness of the electric slope, remains constant. In other words, the
specific conductivity of a solution of an electrolyte varies as the number
of dissociated molecules in a given volume and the speed of the ions.
It increases up to a certain point with the concentration, because the
absolute number of dissociated molecules in a given volume increases.
The molecular conductivity — that is, the conductivity per molecule, or,
strictly, the ratio of the specific conductivity to the molecular concen-
tration— increases with the dilution, because the relative number of
dissociated molecules, as compared with undissociated, increases. At
a certain degree of dilution the molecular conductivity reaches its
maximum, for all the molecules are dissociated. The ratio of the
molecular conductivity of any given solution to this maximum or
limiting value is therefore a measure of the proportion between the
number of dissociated, and the total number of molecules. The molec-
ular conductivity of the salts dissolved in the liquids of the animal
body, for the degree of dilution in which they exist there, is such that
we must assume them to be for the most part dissociated.
Surface Tension. — This is a property of surfaces which is typically
illustrated in such instances as a globule of mercury, a drop of water
on a greasy slide, or a drop of oil suspended in a liquid with which it
does not mix. The tendency of such drops to assume the spherical
form when not large enough to be distorted by gravity is due to the
fact that the surface layer is under a certain tension in virtue of which
it strives to contract and to render the surface of the drop as small as
* It has been shown that the chemical atoms themselves are not homo-
geneous, but are all built up of simpler particles and possess a certain struc-
ture. All atoms, e.g., contain electrons, minute particles charged with negative
electricity. The number of electrons in an atom appears to be not far from
half its atomic weight. Thus in the carbon atom there are 6 electrons, in the
oxygen atom 8, and in the hydrogen atom probably only i. There is
evidence that the electrons in the atom are divided into groups or rings
one within another (Thomson) .
43o ABSORPTION
possible, just as if it were a stretched elastic membrane. The cause
of this tension is to be sought in the mutual attraction exerted by mole-
cules which are very close to each other. This molecular pull is
enormously strong. It has been calculated, for instance, that the
so-called internal pressure which is due to it is in the case of water not
less than 23,000 atmospheres. In the interior of the drop each mole-
cule, being surrounded by other molecules, is pulled by this attractive
force equally in all directions — that is to say, on the whole it is not
pulled at all, since the pulls of all the surrounding molecules balance
each other. At the free surface, on the contrary, the molecules are
pulled towards the surface, but not away from it, and the pull of the
molecules below the surface layer is not balanced by the pull of mole-
cules above it. The resultant tension on this layer is the surface tension.
Changes in the amount of this surface tension in the case of a given
liquid can be produced by bringing gases, solids, or other liquids into
contact with the surface layer — that is, by bringing molecules of other
substances so near the surface molecules of the liquid that they can
attract them, and so to a greater or less degree, depending upon the
nature of the substances, balance the attraction of the molecules
beneath the surface of the drop. Another way in which the surface
tension can be altered is by changing the temperature. The higher
the temperature, the greater is the average velocity with which the
molecules of the liquid are moving, and the greater the average distance
between the molecules (expressed as the expansion of the liquid) . Increase
of temperature therefore causes the molecules, through the kinetic
energy of heat imparted to them, say, from an external source, to
repel each other, and to that extent counteracts their mutual attrac-
tion. Accordingly, at the surface the tension, which, as stated, depends
upon the excess of this attraction acting towards the interior of the
drop, will be diminished. When the temperature is diminished the
surface tension will increase. The surface tension can also be altered
by altering the electrical charge on the surface. An instance of this
is described on another page in connection with the capillary electrom-
eter (p. 702). In such ways, then, the surface tension at the inter-
face where the cells lining the intestine come into contact with the
contents of the gut or with the tissue lymph, or at the interfaces within
the cells where solid and liquid ' phases ' come into contact with each
other or where different liquids touch, may undergo alterations in
either direction. If the tension of the surface is alte-red. the surface
energy or power of doing work inherent in the existence of this tension
will, of course, be altered too. In this way the energy, or a portion of
it, which is unquestionably expended in absorption may be supplied
ultimately at the expense of the chemical energy of cell constituents
or of food substances on their way through the cells, by means of which
the original surface tensions are restored. It has been surmised that
changes of surface tension may also be concerned in the secretion of
glands, in muscular contraction (p. 744), and other functions (Macallum,
Bernstein, etc.).
Adsorption. — Connected with the peculiar properties of surfaces
referred to in the last paragraph are certain phenomena spoken of as
adsorption phenomena. Adsorption is typically seen when a solid in
such a form that the surface is greatly increased (e.g., a fine powder or
a colloidal solution in which the substance is suspended in the form
of exceedingly small particles) is placed in contact with a gas or a
solution. There occurs a diminution in the concentration of the gas
or the dissolved substance, and a corresponding accumulation of it on
the suvl'ace of the solid. Equilibrium is rapidly established, and the
MECHANISM OF ABSORPTION 431
characteristic thing about adsorption is that at the equilibrium-point
the concentration of the dissolved substance (or the gas) on the surface
is immensely greater than in the general mass of the solution. The con-
centration on the surface can, indeed, be increased by increasing the
concentration of the solution, but in a far smaller proportion. Accord-
ing to the thermodynamic law enunciated by Willard Gibbs, sub-
stances which diminish the surface tension must tend to accumulate
at the surface, and substances which increase the surface tension must
tend to diminish in concentration at the surface. If a small quantity
of a substance diminishes the surface tension at a given surface more
in proportion than a larger quantity, not only will there be an accumula-
tion of the substance at the surface, but this will be proportionally
greater for small than for larger concentrations of the substance in the
solution. This characteristic feature of adsorption may thus depend
entirely on surface forces due to the conditions under which the attrac-
tion of the molecules for each other acts at the surface. It has not been
shown, however, that chemical forces due to the interaction of the
electrically charged ions are not also concerned. What is especially
important to point out is that in the tissues of the body there is a
great development of surfaces. The cell walls or cell envelopes come
into contact with the tissue lymph or the contents of the digestive
tube or the secretions in the alveoli of glands on the one side, and the
cell contents on the other, and constitute in the aggregate an immense
surface. The surfaces separating the nuclei from the cytoplasm, and,
above all, the surfaces of the particles of the contents of cytoplasm
and nuclei suspended in colloid solution, offer prodigious opportunities
for such surface phenomena as adsorption.
SECTION II. — MECHANISM OF ABSORPTION.
In the preceding chapter we have traced the food in its progress
along the alimentary canal, and sketched the changes wrought in
it by digestion. We have next to consider the manner in which it
is absorbed. Then, for a reason which has already been explained,
instead of following its fate within the tissues, until it is once more
cast out of the body in the form of waste products, it will be best
to drop the logical order and pick up the other end of the clue — in
other words, to pass from absorption to excretion, from the first
step in metabolism to the closing act, and afterwards to return and
fill in the interval as best we can.
Comparative. — And here, first of all, it should be remembered that
the epithelial surfaces, through which the substances needed by the
organism enter it, and waste products leave it, are, physiologically con-
sidered, outside the body . The mucous membranes of the alimentary,
respiratory, and urinary tracts are in a sense as much external .as the
fourth great division of the physiological surface, the skin. The two
latter surfaces are in the mammal purely excretory. Absorption is
the dominant function of the alimentary mucous membrane, but a
certain amount of excretion also goes on through it. The pulmonary
surface both excretes and absorbs, and that in an equal measure. But
it is by no means necessary that the surface through which oxygen is
taken in and gaseous waste products given off should be buried deep in
the body, and communicate only by a narrow channel with the exterior.
432
ABSORPTION
In the frog the skin is largely an absorbing as well as an excreting
surface ; oxygen passes freely in through it, just as carbon dioxide passes
freely out. In most fishes, and many other gill-bearing animals, the
whole gaseous interchange takes place through surfaces immersed in
the surrounding water, and therefore distinctly external. In certain
forms it has even been shown that the alimentary canal may serve con-
spicuously for absorption and excretion of gaseous, as well as liquid
and solid substances. Still lower down in the animal scale, the surface
of a single tube may perform all the functions of digestion, absorption
and excretion. Lower still, and even this tube is wanting, and every-
thing passes in and out through an external surface pierced by no per-
manent opsnings.
Indeed, even in man the functions of the various anatomical divisions
of the physiological surface are not quite sharply marked off from each
other. Though gaseous exchange goes on far more readily through the
pulmonary membrane than anywhere else, swallowed oxygen is easily
enough absorbed from the alimentary canal and carbon dioxide given
off into it ; and to a small extent these gases can also pass through the
skin. Though water is excreted chiefly by the skin, the pulmonary
and the urinary surfaces, and on the whole absorbed chiefly from the
digestive tract, there is no surface which in the twenty-four hours pours
out so much water as the mucous membrane of the stomach. Under
normal conditions, it is true, by far the greater part of this is reabsorbed
in the intestine, yet in diarrhoea, whether natural or caused by purga-
tives, the intestines themselves may, instead of absorbing, contribute
largely to the excretion of water. Again, although the solids of the
excreta are normally given off in far the greatest quantity in the urine
and faeces (only part of the latter is truly an excretion, since much of
the faeces of a mixed diet has never been physiologically inside the
body at all), yet salts and traces of urea are constantly found in the
sweat, and salts and mucin in the excretions of the respiratory tract.
Further, although the solids and liquids of the food are usually taken
in by the alimentary mucous surface, it is possible to cause substances
of both kinds to pass in through the skin; and a certain amount of
absorption may also take place through the urinary bladder. So that
really it may be considered, from a physiological point of view, as more
or less an accident that a man should absorb his food by dipping the
villi of his intestine into a digested mass, rather than by dipping his
fingers into properly prepared solutions, as a plant dips its roots among
the liquids and solids of the soil ; or that he should draw air into organs
lying well in the interior of his thorax, instead of letting it play over
special thin and highly vascular portions of his skin ; or that the surface
by which he excretes urea should be buried in his loins, instead of lying
free upon his back.
It has been already explained that, although digestion is a
necessary preliminary to the absorption of most of the solids of
the food, we are not to suppose that all the food must be digested
before any of it begins to be absorbed. On the contrary, the
two processes go on together. As soon as any peptone, or, at
least, any amino-acids, have been formed from the proteins, or
any dextrose from the starch, they begin to pass out of the ali-
mentary canal ; and by the time digestion is over, absorption is well
advanced.
Even in the mouth it has already begun, although the amount of
MECHANISM OF ABSORPTION* 433
absorption here is quite insignificant, and it is continued with
greater rapidity in the stomach. Here a not inconsiderable part
of the proteins — at least, in the easily digested form of animal food —
a certain amount of the sugar representing the carbo-hydrates and
diffusible substances like alcohol, and the extractives of meat,
which form an important part of most thin soups and of beef-tea,
are undoubtedly absorbed. Water is very sparingly taken up by
the stomach. It is in the small intestine that absorption reaches its
height. The mucous membrane of this tube offers an immense
surface, multiplied as it is by the valvulae conniventes, and studded
with innumerable villi. Here the whole of the fat, much sugar,
proteose and peptone, or rather the products of the further action
of the ferments of the intestine on these derivatives of the native
proteins, and certain constituents of the bile are taken in. In the
large intestine, as has been already said, water and soluble salts are
chiefly absorbed.
What now is the mechanism by which these various products are
taken up from the digestive tube, and what paths do they follow on
their way to the tissues ?
Theories of Absorption. — Not so very long ago it was supposed by
many that the processes of diffusion, osmosis and nitration offered a
tolerably complete explanation. of physiological absorption. At that
time the dominant note of physiology was an eager appeal to chemistry
and physics to ' come over and help it ' ; and as new facts were dis-
covered in these sciences they were applied, with a confidence that was
almost na'ive, to the problems of the animal organism. The phenomena
of the passage of liquids and dissolved solids through animal membranes,
upon which the work of Graham had cast so much light, seemed to find
their parallel in the absorptive processes of the alimentary canal.
And when digestion was more deeply studied, facts appeared which
seemed to show that its whole drift was to increase the solubility and
diffusibility of the constituents of the food. But as time went on, and
more was learnt of the phenomena of absorption and the powers of
cells, these crude physical theories broke down, and discarded ' vital-
istic ' hypotheses began once more to arouse attention. Then came
the investigations of De Vries, Van 'T Hoff, and others in the domain
of molecular physics, which gave to our notions of osmosis the precision
that was wanted before its relation to many physiological processes
could be profitably discussed. At the present time it must be admitted
that we possess no full explanation of absorption, none which is much
more than a confession of ignorance, and does not itself need to be
explained. Yet some progress has been made at least in defining the
boundary between what is clearly known and what is still dark, and
in showing that familiar physical processes are not without influence.
Some physiologists, impressed with the vast progress of physics and
chemistry, believe that it will eventually become possible to explain
on mechanical and chemical principles all the peculiar phenomena which
we observe in the passage of substances through the walls of the ali-
mentary canal. As an aid to the framing of practical working hypo-
theses this attitude has everything in its favour. Others, taking
account of the number and nature of these peculiarities, oppressed with
the perennial paradox of vital action, incline to the less sanguine view,
28
434 ABSORPTION
that after all physical explanations have been exhausted, the real secret of
the cell will still lurk in some ultimate ' vital ' property of structure or of
function, and still elude our search. The only sense in which this attitude
can be said to be a useful one is that it presents a standing protest against
the acceptance of superficial ' physical ' explanations merely because they
are physical. Both the .optimists and the pessimists, the adherents
of the physical and the adherents of the vitalistic hypothesis, have,
unfortunately, as a rule taken up an extreme position, as if their theories
were mutually exclusive. They agree, however, in admitting that the
phenomena of absorption are essentially connected with the cells that
line the alimentary canal, and not with any more or less inert ' cement '
substance between them. But the one school must confess what the other
proclaims, that while the processes carried on in these cells are definite,
well ordered, and evidently guided by laws, these laws have as yet
for the most part denied themselves to the modern physiologist, with
chemistry in one hand and physics in the other, as they denied them-
selves to his predecessor, equipped only with his scalpel, his sharp eyes,
and his mother- wit. So that in the present state of our knowledge all
we can really say is that, while absorption is certainly aided by physical
processes, like osmosis and diffusion, possibly by physical processes
like imbibition, and is very likely not unrelated to the molecular proper-
ties of surfaces (surface tension, adsorption), it is at bottom the work
of cells with a selective permeability which we do not fully understand,
or at least which we cannot as yet explain in terms of known physical
processes acting through a membrane of known physico-chemical
structure.
Thus, dissolved substances pass with equal ease in either direc-
tion through an ordinary diffusion membrane, but in general they
pass, with the water in which they are dissolved, more readily out
of the intestine than into it. This normal direction of the stream
is still maintained for a considerable time after stoppage of the
circulation, provided that the intestine is kept in good condition —
for example, by being suspended in well-oxygenated blood. Water
or solutions of sodium chloride or sugar disappear from the lumen.
And this is not due to mere imbibition by the intestinal wall, but
the liquid is actually transported across it. The theory that liquids
might be taken up from the gut by imbibition, and the water then
mechanically removed by the blood flowing on the other side of the
imbibing cells, is incompatible with this experiment (Cohnheim).
Nor is it necessary that differences of concentration of the dissolved
substances on the two sides of the absorbing intestinal membrane,
which would permit osmosis and diffusion to go on, should exist.
When the excised intestine of a holothurian was filled with sea-
water and suspended in the same sea-water, its contents continued
to diminish in bulk for hours or entirely disappeared. Here a liquid
identical in composition and concentration with the external liquid
was moved in a definite direction across the wall of the intestine
from the lumen to the exterior surface. In like manner, when a
piece of intestine from a newly-killed rabbit is stretched across a
vessel of salt solution so as to divide if into two separate compart-
ments, the solution continues for a while to leave the compartment
MECHANISM OF ABSORPTION
435
to which the mucosa is turned, and to accumulate in the other. In
the cases mentioned the transportation of the liquid depends upon
the survival of those properties of the mucous membrane which
characterize its elements as living cells. For when the cells that
line the intestine are injured or destroyed, or subjected to the
action of certain poisons, absorption from it is diminished or
abolished. In the dead intestine the characteristic set of the tide
out of the lumen across the mucosa can no longer be observed. It
must be remarked further, in this connection, that in its normal state
the mucous membrane does not take up indiscriminately all kinds
of diffusible substances, or absorb those which it does take up in
the direct ratio of their diffusibility. Nor does it reject everything
which does not diffuse. Albumin, for example, which does not
pass through dead animal membranes, is to a certain extent taken
up from a loop of intestine without change. Cane-sugar (after
inversion) and dextrose are absorbed more rapidly than their
velocity of diffusion would indicate, when compared with inorganic
salts. Glauber's salt diffuses in water fifteen times as fast as cane-
sugar, but cane-sugar is absorbed from the intestines ten times faster
than Glauber's salt. The velocity of absorption is different even
for simple stereoisomeric sugars — i.e., sugars whose molecule, with
the same number of atoms combined in the same way, has a dif-
ferent form (Nagano). Nor is there any clear relation between the
rate of absorption of the various sugars and their osmotic pressure.
Dextrose and cane-sugar are always absorbed in greater amount
than lactose from solutions of the same osmotic pressure. Indeed,
as we shall see, lactose is practically not taken up at all as such
(p. 445), and in concentrated solutions may even cause a reversal
of the normal movement of water, and act as a purgative. Even the
water, organic and inorganic solids of the serum of an animal, are
absorbed from a loop of its intestine when the blood-pressure in the
capillaries of the intestinal wall is considerably greater than the
pressure in the cavity of the gut. Since the serum in the intestine
and the plasma in the capillaries must be isotonic, and practically
identical in chemical composition, the absorption cannot be due
to ordinary osmosis or diffusion. Nor can it be due to filtration,
since the slope of pressure is from the capillaries to the lumen of
the gut (Reid). It is therefore extremely difficult to reconcile this
experiment with any purely physical theory of absorption. The
same investigator, summing up the result of careful experiments on
the absorption of weak solutions of glucose, concludes that, ' with
the intestinal membrane as normal as the experimental procedure
will permit, phenomena present themselves which are as distinctly
opposed to a simple physical explanation as those previously
studied in the absorption of serum.'
There is also evidence that even during the absorption of liquids
436 ABSORPTION
which undergo no chemical changes in the gut — e.g., salt solutions
of different kinds and different concentrations— chemical energy
must be transformed, and on no mean scale, in the intestinal
mucosa, for the consumption of oxygen and the production of
carbon dioxide by the intestine is markedly increased (Brodie and
Vogt).
It may be taken, then, as quite certain that in absorption from
the alimentary canal an essential factor is the activity of the living
cells of the mucosa, which, in some way at present unknown, main-
tain the ' set of the tide ' from the lumen to the bloodvessels (or
lymph spaces), whether the slope of concentration of the dissolved
substances favours or opposes it, or when the concentration is the
same on both sides of the membrane. It is even probable that this
action of the cells is much the most important of all the factors
involved. It would be highly misleading, however, to assume that,
because this is so, other factors — osmosis, diffusion, possibly even
nitration due to differences of pressure caused by the intestinal
movements or the contractions of the muscular fibres of the villi
(p. 443) — are of necessity negligible. On the contrary, these other
factors cannot be adequately taken account of, nor can there be
any possibility of assigning to them their proper value until it is
recognized that their influence in absorption from the digestive
tract is never under ordinary conditions expressed as a simple and
uncomplicated effect, such as may be observed in experiments with
dead membranes, but, on the contrary, is constantly overlaid,
thwarted, or totally reversed, by the special action of the cells.
For this reason the discussion of the mechanism of absorption under
the time-honoured captions of ' mechanical or physical theory '
versus ' physiological or vital theory/ as if the process must of
necessity be purely ' physical ' or purely ' vital,' has lost interest.
It may be confidently assumed, indeed, that just because the
physiological factor is so dominant, the familiar physical forces
must often appear to exert a smaller influence than is really the
case, and that, could we disentangle the currents which they create
and sustain from that steady drift of material out of the lumen of
the gut maintained at the expense of its chemical energy by the
still unknown machinery of the cells, we should be impressed with
the magnitude rather than the insignificance of their total effect.
The following attempt by Hober to analyze on these lines an old
experiment of Heidenhain, which the latter observer had interpreted
as showing that diffusion and osmosis play no essential part in absorp-
tion from the alimentary canal, is of interest in this connection. A
loop of small intestine was tied off at both ends, but its circulation was
not otherwise interfered with. Solutions of sodium chloride of dif-
ferent strengths were introduced into the loop, and in each observation
after fifteen minutes the contents of the loop were recovered and
analyzed for the chloride.
MECHANISM OF ABSORPTION
437
Introduced.
Recovered,
c.c.
Parcentage of
NaCl.
Total NaCl in
Grammes.
C.C.
Percentage of
NaCl.
Total NaCl in
Grammes.
I2O
0-30
0-36
18
O-6O
O'loS
120
0-50
0-60
35
0-66
0-230
II7
i-oo
1-17
75
0-90
0-670
120
1-46
i'75
109
1-20
I-3IO
Here it is seen that, from the markedly hypotonic solutions of the
first two observations, sodium chloride was absorbed, of course, along
with much water. But from the strongly hypertonic solution of the
last observation some water was also taken up, instead of water passing
into it from the blood. The suggested explanation of these and other
data yielded by the experiment is that an osmotic stream of water out
of the loop into the blood is established on introduction of the hypo-
tonic solutions, which raises their percentage of salt, while in the case of
the hypertonic solution a diffusion stream of sodium chloride is estab-
lished in the same direction, and its salt content falls. The volume of
the hypotonic solutions in the loop rapidly diminishes because the
osmotic current conspires with the normal ' physiological ' drift from
the lumen outwards. In this drift both salt and water are involved,
as if the cells were filters which maintained through expenditure of
their own energy a slope of hydrostatic pressure from free surface to
depth. The hypertonic solution diminishes only slowly in bulk, be-
cause the ' physiological ' current out of the lumen is opposed by the
osmotic stream of water into the lumen. Nevertheless, even the hyper-
tonic solution is gradually absorbed, because the pull of the cells — the
suction, if it may be so expressed, of the cellular pump — is powerful
enough to overcome the osmotic current and to force water up the
slope into the blood or into the tissue liquid, whose osmotic pressure is
not much more than half that of the solution.
Permeability of the Intestinal Epithelium and Lipoid-Solubility
of Absorbed Substances. — If the. cells of the intestinal mucosa are
to move materials out of the lumen of the gut, it is obvious that
these materials must first be able to enter the cells. The ease or
difficulty with which different substances are absorbed may there-
fore depend upon the degree in which the cells are permeable for
them. The question of the factors on which the permeability of
cells depends has already been discussed to some extent in the case
of the coloured blood-corpuscles. A famous theory attributes the
degree of permeability of erythrocytes and many other animal and
plant cells to given substances to the degree of the solubility of
these substances in the lipoids which are supposed to form the
essential constituents in the outer layer or envelope of cells (Overton)
Substances which are readily soluble in lipoids are supposed to gain
an easy entrance by going into solution in the envelope ; those which
are insoluble in lipoids are checked at the boundary. Attempts
have been made to apply this theory to the explanation of selective
438 ABSORPTION
absorption by the intestine, but without much success. The very
fact that the theory is held to apply to practically any cell greatly
circumscribes at the outset its power of dealing with cells like those
lining the intestine, which are adapted to absorb nutrient materials
for all the body, and must necessarily differ in their permeability
from cells adapted for some limited function involving only a
limited and specialized nutritive exchange. Thus sodium chloride
practically does not penetrate the red blood-corpuscles, the muscle
fibres, and many other tissue elements. It is a lipoid-insoluble sub-
stance, and the lipoid theory says that this is the reason why it
penetrates these cells with such difficulty. But sodium chloride
must and does penetrate the intestinal mucosa, and with consider-
able ease, in order that the body, especially its extracellular liquids,
may obtain a sufficient supply of this indispensable material. It is
still a lipoid-insoluble substance, and pays no heed to the lipoid
theory at all. It is perfectly true that some substances — e.g., ethyl
alcohol — which are much more soluble in lipoids than sodium
chloride, are also even more readily absorbed from the intestine.
It has been stated also that, as regards the velocity of their absorp-
tion, the three alcohols, glycerin, erythrite, and mannite, are related
to each other in the same way as in regard to their lipoid-solubility.
There is, of course, some reason for this, and also some reason why
ethyl alcohol is taken up more easily than salt, but we do not know
that it has anything to do with lipoid-solubility. If there is a
lipoid layer at the free ends of the cells covering the villi, it is very
possible that a substance soluble in lipoids may be able to enter cells
which would otherwise have denied it entrance. It may even inflict
temporary or permanent injury on the cells in doing so, and may
thus be taken up in greater amount than by normal cells, and this
possibility has to be reckoned with in giving a physiological value
to experiments with materials essentially foreign to the intestine,
and to which it cannot have developed any adequate adaptation.
For the essential food materials it is quite certain that, apart from
any general relations of cell envelope and environing liquids which
are common to the intestinal and to other cells, special relations of
an adaptive nature have been developed between the intestinal cells
and the very special liquids, elsewhere unknown in the body, with
which they come in contact in the lumen of the gut. It is unlikely
that the mucosa has developed a special adaptation for lipoid-
soluble food materials; it must have developed an adaptation for
such food materials, lipoid-soluble or not, as have been offered to
it through countless ages, and as are necessary for the nutrition of
the organism.
But if it be true that the action of the columnar epithelium of the
intestinal mucous membrane in the absorption of the food is in the
main a process of selective secretion such as is found in glandular
MECHANISM OF ABSORPTION 439
organs, an action which we may perhaps describe as making use
of purely physical processes, but not mastered by them, the possi-
bility must be admitted that in the cells of endothelial type which
line the serous cavities, the lymphatics, the bloodvessels, the alveoli
of the lungs, and the Bowman's capsules of the kidney (p. 489), the
element of secretion may be less marked, and more overshadowed
by the physical factors. And it may very plausibly be urged that
changes of considerable physiological complexity can only be
wrought on substances that have to pass through a cell of con-
siderable depth, while a mere film of protoplasm suffices for, and
indeed favours, mechanical filtration and diffusion. We have
already seen (p. 264), in the case of the lungs, that whatever the
complete explanation may be of the gaseous exchange which takes
place through the alveolar membrane, physical diffusion undoubtedly
plays an important part. We shall see, too (p. 500), that in the case
of the kidney the endothelium of the Bowman's capsule, although
by no means devoid of selective power, does seem to have allotted to
it a simpler task than falls to the share of the ' rodded ' epithelium.
Absorption from the Peritoneal Cavity. — Further, it has been stated
that interchange between blood-serum, circulated artificially in the
vessels of dogs and rabbits which have been dead for hours, and
liquids introduced into the peritoneal cavity, is essentially the same
as in the living animal, and can be explained on purely physical
principles (Hamburger). But there is one experiment, at any rate,
which is certainly difficult so to explain — viz., the absorption from
the peritoneal cavity of sodium chloride solution isotonic with the
blood-serum, an absorption which goes on with considerable
rapidity. Starling has supposed that this is due to the circum-
stance that the proteins of the serum exert osmotic pressure, the
peritoneal membrane being almost or altogether impermeable for
them in comparison to its permeability for the salt solutions. In
consequence, water passes into the bloodvessels from the peritoneal
cavity. The solution thus becomes more concentrated as regards
sodium chloride, some of which accordingly enters the blood
by diffusion, and so on. But even isotonic serum is absorbed
from the peritoneal cavity, and it seems to savour of special pleading
to suggest, as has been done, that this takes place through the
lymphatics, and not at all through the bloodvessels.
Up to a certain point an increase in the intraperitoneal pressure
favours absorption, but beyond this it hinders it by interfering with
the circulation. The removal of a portion of the fluid in this con-
dition facilitates the absorption of the rest — a fact which has long
been applied in the operation of tapping. Ligation of the thoracic
duct has little effect on the fate of liquids injected into serous
cavities, since the bloodvessels play the chief part in their absorp-
tion, just as strychnine, when injected under the skin — i e., into
440 ABSORPTION
the lymph spaces of areolar tissue — is taken up by the blood and
does not appear in the lymph.
But even if we admit that substances can pass, by physical pro-
cesses alone, from serous cavities into the blood, and from the blood
into serous cavities, this has little bearing upon the question of
intestinal absorption. For we can hardly put anything into the
peritoneal cavity which is not foreign to it. It was never intended
to come into contact with the hundred and one solutions, extracts,
suspensions, and what not, which the industrious experimenter has
offered to its unsophisticated endothelium. It cannot possibly have
developed any high degree of ' selective ' power. In the intestine
everything is different. The mucosa is adapted to come into
contact with an immense variety of materials, all kinds of food-
substances mingled with many kinds of refuse, the products of
the action of numerous digestive ferments, and of a vigorous and
varied bacterial flora. All these it has to sift and try. It cannot fail
to have properties which suggest a severe and searching selection.
The difference between a serous cavity and the intestine is well
illustrated by the following experiment, in which the changes in the
composition of a hypotonic (3 per cent.) solution of dextrose introduced
into the peritoneal sac and into a loop of intestine respectively were
compared (Cohnheim).
Introduced.
After
Recovered.
Peritoneum -
50 c.c.
90 mins. -
19-5 c.c., containing i per cent,
dextrose and 0-55 per cent.
NaCl.
Intestine - -
44 »
25 ..
19 c.c., containing 3-8 per cent,
dextrose and 0-04 per cent.
NaCl.
Here the water and sugar are both taken up from the intestine and
the peritoneal cavity; but while the sugar concentration in the serous
sac falls markedly, as ought to be the case if the sugar is diffusing into
the blood along the slope of concentration, the percentage of sugar in
the intestine actually increases. Still more striking is the fact that
sodium chloride accumulates in the peritoneal liquid in a concentration
obviously tending to equality with that of the blood, as would happen
if the peritoneal lining were a dead diffusion membrane. On the other
hand, practically no sodium chloride passes into the lumen of the gut.
Closely connected with the question of absorption from and
secretion (or transudation) into the serous cavities is the question
of the factors concerned in the formation of the lymph (which will
be considered in the next chapter), even although recent researches
throw grave doubt on the common view that these sacs are merely
expanded lymph spaces, and indicate that the liquid found in them
has a different origin from lymph.
ABSORPTION OF THE VARIOUS FOOD SUBSTANCES 44*
•>. ••?", » te*«>i
SECTION III. — ABSORPTION OF THE VARIOUS FOOD SUBSTANCES.
Absorption of Fat — How the Fat gets into the Intestinal Epithelium.
— It has been already mentioned that fat is split up in the intestine
into the corresponding alcohols (mostly glycerin) and fatty acids,
but it has been a subject of discussion whether it all undergoes this
change or only a portion of it. The common view has long been
that the greater part of the fat escapes decomposition, and, after
emulsification by the soaps formed from the liberated fatty acids,
is absorbed as neutral fat by the epithelial cells covering the villi. If
an animal is killed during digestion of a fatty meal, these cells are
found to contain globules of different sizes, which stain black with
osmic acid, are dissolved out by ether, leaving vacuoles in the cell
substance, and are therefore fat (Fig. 172). It has always been
difficult to explain how droplets of
emulsified fat could get into the
interior of the epithelial cells, al-
though, perhaps, no more difficult
than to explain the passage of living
tubercle bacilli from the contents of
the intestine into the chyle of the
thoracic duct — a fact which has been
clearly demonstrated (Ravenel) . The
fat is certainly contained within the
cells, and not between them. When
fat is found in the cement sub-
stance between the cells, it has been
mechanically squeezed out of them
by the shrinking of the villi in
preparation. This difficulty is obviated if we suppose that the
whole of the fat is split up in the intestine, the products being
absorbed in solution, the glycerin as such, and the fatty acids either
as soaps or in the free state, or partly free and partly saponified.
If this is the true theory — and the evidence of its truth has of late
years been continually growing — neutral fat must again be built
up in the epithelial cells from the absorbed glycerin and the fatty
acids or soaps. Now, it has been shown that when an animal is fed
with fatty acids they are not only absorbed, but appear as neutral
fats in the chyle of the thoracic duct, having combined with glycerin
in the intestinal wall; and the epithelial cells contain globules of
fat, just as they do when the animal is fed with neutral fat. Further,
it is known that fat-splitting goes on in the alimentary canal to a
much greater extent than would be necessary merely for the forma-
tion of a quantity of soap sufficient to emulsify the whole of the fat
in the food. Indeed, at certain stages of digestion most of the
Fig. 172. — Mucous Membrane of
Frog's Intestine during Absorp-
tion of Fat (Schafer). ep, epithe-
lial cells; sir, striated border;
C, lymph corpuscles; /, lacteal.
442 ABSORPTION
fatty material, both in the small and large intestine, has been found
to consist of fatty acids. The reversibility of the reaction under
the influence of lipase, which has already been alluded to, does not
enter into the question so far as fat-splitting in the intestine is con-
cerned, for the products of the reaction can be absorbed as quickly
as they are formed. To clinch the matter, it has been proved that
when mixtures of paraffin and fat, which can be emulsified in a
watery solution of sodium carbonate, are eaten, the paraffin is com-
pletely excreted with the faeces, while the greater part of the fat is
absorbed. And fatty substances which are not easily split up and
saponified (for example, lanolin, the fat of sheep's wool, a mixture
of compounds of fatty acids with isocholesterin, a substance closely
related to cholesterin and allied bodies) are not absorbed even when
they are easily emulsified. Even fats with a melting-point far
above the temperature of the body can be absorbed after being split
up. The palmitate of cetyl alcohol, the chief constituent of sper-
maceti, melting at 53° C., was absorbed to the extent of 15 per
cent., 85 per cent, being excreted in the faeces. It appeared as
palmitin in the chyle of a human being flowing from a fistula, the
palmitic acid having been absorbed as such, or as a sodium soap, and
having then united with glycerin to form the neutral fat, palmitin.
Some observers have endeavoured to show that the fat is absorbed
without change by introducing into the intestine fat stained with
dyes, such as alkanna red or Sudan III., which are insoluble in
water. The stained fat was found in the epithelial cells of the villi,
in the lacteals, and, in the case of a patient suffering from chyluria,
in the urine. But this evidence is not conclusive, for it has been
shown that the pigments might easily have been absorbed after
decomposition of the fat, since, although insoluble in water, they are
soluble in fatty acids, and therefore to some extent in the intestinal
contents, and readily pass into the lymph.
As already pointed out, the bile plays an important part in the
solution of the fatty acids, which may form loose compounds with
the amide group of the bile-acids. In these loose combinations,
soluble in water, the fatty acids can be absorbed from the intestinal
contents (Pfliiger). In whatever way the fat which can be seen
in the epithelial cells during absorption of fat gets into them, it
must be carefully noted that there is no quantitative proof that it
represents all or even the greater part of the absorbed fat. So far
as microscopic observations go, much of the fat may pass through
the mucosa in the form of soluble decomposition products without
appearing in particulate form in the epithelium.
How the Fat gets out of the Intestinal Epithelium. — Leucocytes
have been asserted to be active agents in the absorption of fat.
They have been described as pushing their way between the
epithelial cells, fishing, as it were, for fatty particles in the juices
ABSORPTION OF THE VARIOUS FOOD SUBSTANCES 443
of the intestine, and then travelling back to discharge their cargo
into the lymph. This view, however, is erroneous. But, although
the leucocytes do not aid in the absorption of fat from the intestine,
they may take up a certain amount of it from the epithelial cells,
and convey it through the spaces of the network of adenoid tissue
that occupies the interior of the villus, to discharge it into the
central lacteal, where it mingles with the lymph and forms the so-
called molecular basis of the chyle. It has been supposed that a
part of the fat may reach the lacteal in another way. The con-
traction of the smooth muscular fibres of the villus and the peristaltic
movements, of the intestinal walls, which alter the shape of the
villi, alter as well the capacity of the lacteal chamber, and so
alternately fill it from the lymph of the adenoid reticulum, and
empty it into the lymphatic vessel with which it is connected. By
this kind of pumping action the passage of fat and other substances
into the lymphatics may be aided. There is, however, no proof
that all the fat accumulated in the intestinal epithelium leaves
it without further change. It is quite as probable that the lipase
which is known to be contained in the cells again hydrolyses the
fat, or a portion of it, and that the constituents then pass out into
the lymph, or even in part into the blood. In the dog most of the
fat goes into the lacteals, and thence by the general lymph-stream
through the thoracic duct into the blood. And in man the chyle
collected from a lymphatic fistula contained a large proportion of
the fat given in the food (Munk). But this bare statement would
be misleading if we did not add that the fat taken in can never be
entirely recovered in the chyle collected from the thoracic duct.
A small fraction of the deficit might be accounted for as fat directly
used up for the nutrition of the intestinal wall itself. But even after
ligation of the thoracic and right lymphatic ducts a large proportion
of a meal of fat (32 to 48 per cent.) is absorbed from the intestine,
obviously by the channel of the bloodvessels, since the fat-content
of the blood increases up to, it may be, six times the highest amount
present in the blood of fasting animals. The statement that only
fatty acids can be absorbed under these conditions is erroneous
(Munk and Friedenthal).
A dog normally absorbs 9 to 21 per cent, of the fat in a meal in
three to four hours; 21 to 46 per cent, in seven hours; and 86 per
cent, in eighteen hours (Harley). After excision of the pancreas
the absorption of fat is hindered, though not abolished. More fat,
indeed, can be recovered from the intestine than is given in the food.
This at first sight paradoxical result is explained by the well-estab-
lished fact that a certain amount of fat is normally excreted into
the intestine.
Mechanism of Fat Synthesis in the Intestinal Mucosa. — As to the
manner in which the synthesis of the fat in the intestinal epithelium
444 ABSORPTION
is accomplished, the most fascinating theory is that which attributes
it to the reversed action of lipase, possibly the very same lipase as
originally split it up in the intestine. The reversibility of the action
of various enzymes under changed conditions, especial] 3^ changes in
the relative concentration of the bodies concerned in the reaction,
has been previously mentioned. It has been shown, e.g., that the
pancreas, intestinal mucous membrane, lymph glands, etc., and
even cell-free extracts of these organs have the power of synthesizing
the ester ethyl butyrate from butyric acid and ethyl alcohol
(p. 338), as well as the power of decomposing the ester into the
fatty acid and the alcohol. Moore, however, states that in the
case of ordinary fats the synthesis takes place in the intestinal wall
only in situ, and while the circulation is going on. In the intestinal
mucosa the greater part of the fatty acid is already combined with
glycerin as neutral fat, although considerable quantities of free fatty
acid are also present. In the lymph coming directly from the
mesenteric glands practically the whole of the fatty acids are in
the form of neutral fat.
An additional, and in some respects even more remarkable, illus-
tration of the synthesizing powers of the intestinal wall is the dis-
covery of Munk, already referred to (p. 441), that fatty acids given
by the mouth appear in the lymph of the thoracic duct as neutral
fats, having somewhere or other, in all probability on their way
through the epithelium of the gut, been combined with glycerin.
Since, however, the amount of neutral fat recovered from the
thoracic duct is not equivalent to more than one-third of the fatty
acids given, it has been suggested that this synthesis of fat is only
apparent, and that the whole of the fat which appears in the chyle
after a meal of fatty acids comes from the fat excreted into the
intestine (Frank), which is increased when fatty acids are given by
the mouth. But the suggestion is more ingenious than the evidence
advanced in its support is convincing. And, as we have seen
(p. 443), a part of the deficit may be accounted for by absorption
directly into the bloodvessels.
In concluding our review of the absorption of fat, certain general
considerations which have a close relation to the question may be
alluded to. There is some reason to think that the lipises are
enzymes less finely adjusted to minute differences in the structure
of the fats on which they act than other digestive ferments — eg.,
maltase or lactase, to details in the chemical structure of their
substrates. If this be so, a very few lipases, or even a single one,
may suffice to accomplish all the enzymatic changes which occur
in the fats both in the lumen of the intestine and in all the various
tissue cells. At the same time the possible variation in those decom-
position products which constitute the ' building-stones ' of the fats
is less than in the case of, say, the proteins. Two consequences
ABSORPTION OF THE VARIOUS FOOD SUBSTANCES 445
follow as regards the absorption of fat: (i) Each cell may be capable
of dealing with the original neutral fats of the food, and of adapting
them to its needs by decomposing and resynthesizing them so far
as is necessary in its own substance. In this case it would not be
necessary for assimilation by the cells that the fats should be com-
pletely split or even split at all in the alimentary canal, however
important this might be for their absorption from its lumen.
(2) If it were necessary for absorption that decomposition of the
fats should take place in the lumen of the digestive tube, the whole
of the fat, or at any rate such portion of it as was not at once needed,
might without disadvantage for the tissues be resynthesized after
absorption. It is not difficult to see that it might even be advan-
tageous that not only the relatively fixed reserve in the fat cells,
but also what might be termed the floating or circulating reserve
constituted by the emulsified fat in the blood should be in the
insoluble form of neutral fat.
Absorption of Carbo- Hydrates. — Carbo-hydrates are normally
absorbed from the alimentary canal only in the form of mono-
saccharides, such as dextrose, levulose or fructose, and galactose,
but especially dextrose. These monosaccharides are readily
formed from polysaccharides like starch and dextrin, and the disac-
charide maltose, which they yield on digestion with amylase, as
well as from disaccharides like cane-sugar and lactose, by the fer-
ments already studied. That, as a matter of fact, the hydrolysis
in the intestine must convert practically all the carbo-hydrate into
monosaccharides before absorption, can be shown in various ways.
The ferment lactase, while present in the small intestine of all
young mammals, is regularly absent in some mammalian groups
in the adult. In other species, including man, it is found in some
adults, but not in all. In birds and other animals below the mam-
mals, it has not hitherto been found at any age. It has been sur-
mised that these differences depend upon the presence or absence
of lactose (milk) as a regular constituent of the food. (But see
p. 410.) If, now, lactose is introduced into a loop of intestine in an
animal which does not possess lactase — e.g., an adult rabbit — it is
not absorbed, but remains in the lumen till it is at last decomposed
by bacterial action. In animals in which lactase is present the
lactose is rapidly absorbed. Maltose is easily taken up from the
intestine because of the action of the ferment maltase, which is the
most widely spread of all the inverting ferments. The dextrose formed
by the maltase is so rapidly absorbed that none, or only traces, of it
can be detected in the contents of the intestinal loop. But if absorp-
tion be interfered with by injuring the intestine, maltose disappears,
and the dextrose produced from it accumulates in the lumen. The
reason for the discrimination exercised by the intestinal mucosa in
favour of the monosaccharides becomes apparent when an attempt is
446 ABSORPTION
made to circumvent it by injecting the sugars parenterally — i.e., into
subcutaneous or intramuscular connective tissue, into a serous sac,
or directly into the blood. Cane-sugar and lactose so introduced
are excreted unchanged in the urine. Dextrose, levulose, and
galactose are used up in the body, and some maltose likewise,
thanks to the presence of maltase in the blood and tissues. The cells
of the body in general wall burn only monosaccharides, and not di- or
poly-saccharides. Galactose and fructose are probably first con-
verted into dextrose before being utilized by the tissues, a change
which can also be readily induced in the test-tube. Therefore the
intestine admits the simple, but rejects the more complex sugars.
It is only in the presence of abnormally great quantities or ab-
normally great concentrations of the sugars which are not directly
utilizable that they are to a certain extent taken up unaltered,
to be for the most part quickly excreted as such (p. 540). In like
manner we have seen that the rtative proteins can, so to speak,
force their way by storm through the intestinal mucosa when
offered to it in exceptionally large amount. The sugar absorbed
from the intestine passes normally into the rootlets of the portal vein,
not into the chyle, for no increase in the quantity of that substance
in the contents of the thoracic duct takes place during digestion,
while the sugar in the portal blood is increased after a starchy meal.
The blood of the portal vein of a dog in the fasting condition con-
tained 0-2 per cent, of dextrose. During absorption of a meal rich
in carbo-hydrates it contained as much as 0-4 per cent. In the
lymph issuing from the thoracic duct the amount was the same in
both conditions — viz., 0-16 per cent. In a case of lymph (chyle)
fistula in a human being, where almost all the lymph from the
digestive tract escaped through the fistula, out of 100 grammes of
carbo-hydrate taken (50 grammes starch and 50 grammes sugar),
only £ gramme, or not I per cent, of the sugar corresponding to the
carbo-hydrates of the food, could be recovered in the chyle. But
when a large amount of a dilute solution of sugar is introduced into
the intestine, some of it is taken up by the lacteals.
Absorption of Water and Salts. — The main channel for absorption
of these is the bloodvessels of the intestine. As much as 3 to 5 litres
of water can be absorbed in a day in the intestine of a healthy man,
exceptionally even 6 to 10 litres, without the faeces altering their
normal consistence. Absorption of the water and dissolved salts
may theoretically take place either through the epithelial cells (intra-
epithelial absorption), or between the cells (interepithelial absorp-
tion). According to Hober, most metallic salts (silver, mercury,
lead, bismuth, copper, manganese, etc.) are absorbed interepitheli-
ally, while iron salts form an exception, and pass into the epithelial
cells. The distinction between interepithelial and intra-epithelial
absorption does not rest upon an absolutely sure foundation. Yet
ABSORPTION OF THE VARIOUS FOOD SUBSTANCES
447
it is probable that everything which is useful in the nutrition of
the body is taken up by the cells, while such substances as metallic
salts which are foreign to the organism, and are denied entrance
into the cells, may pass in small amount between them, their passage
being perhaps associated with more or less injury to the interstitial
substance. The vigilant selection exercised by the mucosa is well
illustrated by the facts that, although manganese and iron are
chemically so closely related, iron, which is necessary for the
formation of the blood-pigment, is absorbed in immensely greater
amount than manganese; and that chlorides, especially sodium
chloride, are readily taken up, sulphates with difficulty. Iron is
absorbed by the bloodvessels, but also to some extent by the lacteals.
From the blood it is carried to various organs, especially the spleen
and liver. There is reason to believe that the eosinophile leucocytes
take some share in its transportation.
It was supposed by Bunge that only organic compounds of iron
could be absorbed, and that the undoubted benefit derived from
the administration of inorganic iron compounds, such as ferric
chloride, in chlorosis, was due not to their direct absorption, but
to their shielding the organic compounds from the attack of the
sulphuretted hydrogen in the intestine (p. 424). But this theory
has been shown to be inconsistent with the facts. For instance,
after the administration of salts of iron, the iron in the blood,
liver, spleen, and other organs increases, but there is no accumula-
tion of iron in the liver of an animal to which salts of manganese
have been given, although these are equally decomposed by sul-
phuretted hydrogen.
Absorption of Proteins. — 'The proteins of the food or their digested
products also pass directly into the blood-capillaries which feed
the portal system. For it has been shown that after ligature of
the thoracic duct protein substances are still absorbed from the
intestine, and the urea corresponding to their nitrogen appears in
the urine. The total nitrogen in the chyle flowing from a fistula
of the thoracic duct in a man was not found to be increased during
the digestion of protein food. The quantity of chyle escaping in a
given time was also unaffected, whereas during the digestion of fats
it was greatly augmented (Munk).
Although a certain amount of egg-albumin, serum-albumin, alkali-
albumin, and other native or slightly altered protein substances
can be absorbed as such by the small, and even by the large, in-
testine, there is no evidence that, under ordinary conditions, this
mode of absorption is of any practical importance in nutrition,
although in another relation it may possess a certain interest (p. 32),
For when native proteins, with the possible exception of the
serum proteins from an animal of the same species, are introduced
' parenterally,' so that they do not reach the tissues by way of
448 ABSORPTION
the alimentary canal, they behave in a very different manner from
the same proteins when given by the mouth. One notable differ-
ence is that the parenterally administered proteins give rise in
general to the formation of antibodies — -e.g., specific precipitins^
(p. 31). This is not the case when they are administered per os,
unless, like raw egg-white, which, as already mentioned (p. 404),
evokes no secretion of gastric juice, they remain long undigested
in the alimentary canal, when an amount sufficient to cause the
production of precipitins may eventually be absorbed unaltered.
This has also been shown by means of the anaphylactic reaction.
Secondly, they are not, as a rule, utilized in the metabolism of the
body, or are utilized very incompletely. Egg-albumin, for instance,
when injected into the blood, is excreted in the urine. It has been
previously pointed out that the various proteins differ remarkably
not so much in the kinds as in the relative quantities of the amino-
and diamino-acids which can be obtained from them (p. 2). This
is unquestionably one important reason why the food proteins are —
for the most part, at any rate — so thoroughly hydrolysed before
absorption. Another may be that it is easier for the intestine to
take up the small molecules of the decomposition products than
the large colloid aggregates of the original protein solutions.
So far as the first reason is concerned, the degree of decomposi-
tion need not be the same for all the food proteins, although all
must be decomposed, for even among the proteins the products of
whose hydrolysis do not exhibit qualitative differences, no two
have hitherto been discovered which show the same quantitative
relations among the ' building-stones. ' A new house has to be built
from the materials of an old one. How far the work of demolition
must be carried will depend upon the difference between the plans
of the two houses. Sometimes the main part of the old building
may be saved, and only the wings require reconstruction. In like
manner it is conceivable that the central group or nucleus of the
molecule of a given food protein may be identical with that of a
given body protein, and that only the side-chains may be so different
that they must be broken up and reconstructed. Or, again, the
whole architectural plan of the new house may be so distinct from
that of the old that the only feasible method is to completely
demolish the latter, and then to use the individual bricks in the
new construction; just as a protein in the food may differ so
radically from a tissue protein into which it is to be transformed
that it must be decomposed into the simplest products of proteo-
lysis before the reconstruction of the molecule can begin. It is not
known what the minimum degree of hydrolysis is which will permit
of effective absorption and utilization. But it would seem that it
must be very complete. Even a body so simple in comparison with
the proteins as the tripeptide (p. 2) alanyl-glycyl-tyrosin, con-
449
taining only three ' building-stones,' can only be changed into the
tripeptide alanyl-tyrosyl-glycin by first hydrolysing it into its three
components and then synthesizing these afresh. On the other
hand, in obtaining the tripeptide glycyl-tyrosyl-alanin from alanyl-
glycyl-tyrosin, the dipeptide group glycyl-tyrosin can remain un-
decomposed, and it is only necessary to split alanin off and link it
up to the dipeptide to obtain the desired glycyl-tyrosyl-alanin
(Abderhalden). There can be no doubt that by far the greater
part, if not the whole, of the proteins of the food is first changed into
proteoses and peptones. But proteose and peptone are absent
from the blood, and, indeed, when injected into the blood they
are excreted in the urine. When injected in larger amount, they
pass also into the lymph, from which they gradually reach the blood
again, and are eventually, as before, eliminated by the kidneys.
The clear inference is that if they are absorbed as such from the
alimentary canal, they must be changed in their passage through its
walls. The fact that a portion at any rate of the peptones and
proteoses is decomposed into amino-acids, etc., in the lumen
of the intestine has been already alluded to. It is certain that
this portion is a very large proportion of the whole, although the
question how much, if any, of the peptone passes as such from the
lumen into the mucosa must still be left undecided. It is true
that along with amino-acids peptones are always found in the
intestine during the digestion of protein, and the quantity of
amino-acids actually present in the lumen at any moment may
DC small in proportion to the quantity of peptone. But this is
precisely what is to be expected if the peptone as such is incapable
of absorption. For the easily absorbed amino-acids will disappear
from the gut as fast as they are formed, leaving behind the peptone
for further hydrolysis. The fact that all the amino-acids which the
proteins are capable of yielding can be detected in the contents of
the intestine, including even those which appear late and, as it
were, reluctantly in artificial digestion, is a proof that the decom-
position of the protein goes fast and far in the alimentary canal.
If it is not complete, if some of the partially hydrolysed protein is
taken up by the mucous membrane in the form of peptones or
possibly even of proteoses, it would seem that this is similarly
decomposed by the action of erepsin in the intestinal wall. y
It has been stated that during the digestion of a protein meal the
mucosa of the stomach and intestine contains proteose and pep-
tone, while none is present in the muscular coat or in any other
organ. They rapidly disappear from a portion of the mucous mem-
brane kept at a temperature of about 40° C. outside of the body, and
their disappearance is due, not to their regeneration into serum
proteins, as was once supposed, but to their decomposition by the
erepsin. We must suppose that the serum and organ proteins are
29
450 ABSORPTION
built up from the products of this decomposition. But whether the
mucosa of the alimentary tract is especially a seat of the synthesis
is unknown (p. 573). On a priori grounds, it is at least equally
probable that it occurs in all the cells of the body, each one building
up for itself the particular kind of protein which it needs. The
direct way of testing the question would be to examine the blood
coming from the intestine during the absorption, of proteins, and to
determine quantitatively any changes which might have occurred in
the nitrogenous constituents. But the flow of blood through the
intestine is so great, the absorption of the digestive products so
gradual, and their removal from the blood by the tissues, in all
probability, so rapid, that there is no reason for surprise that till
lately the results of such determinations were ambiguous. Leathes,
however, showed some time ago that when peptone, proteose, or the
final products of tryptic digestion are introduced into a ligated
segment of a dog's small intestine, there is always, when absorption
occurs, an increase in the nitrogenous substances in the blood, in the
form of compounds which are not precipitated by tannic acid, and
therefore are neither native proteins nor proteose. Urea accounts
for about one-half of the increase ; the rest he considered to represent
probably amino-acids and similar substances. Quite recently it
has been conclusively demonstrated by improved methods that the
digestion of protein is associated with an increase of non-protein
nitrogen in the blood, due, there is every reason to believe, to amino-
bodies derived from the hydrolysed protein (Folin and Denis, Van
Slyke, Abel). This proves for the mammal what had been deduced
by Cohnheim for a much lower form from experiments made on the
intestines of certain octopods, which, when excised and suspended
in the oxygenated blood, will live for many hours. A solution of
peptone was introduced into the isolated intestine, and after twenty
hours the crystalline products, leucin, tyrosin, lysin, and arginin,
were found in the blood. In the intact animal none of these bodies
could be detected in the blood (Cohnheim). The inference was
that protein in these animals is absorbed in the form of amino-acids,
etc., which are then carried to the tissues and utilized there. In
the mammal the same thing appears to be true. For the increase
in the amino-acids during digestion of proteins occurs not only in
the portal blood, but in the blood of the general circulation. So
that, although a part of the absorbed amino-bodies may be removed
by the liver, a portion at least is available for the tissues in general.
That the tissues actually take up such decomposition products of
proteins is indicated by the fact that during and after the digestion
of protein in a loop of intestine the non-protein nitrogen of the
tissues is increased (Folin). It may be that some of the proteose
and peptone are regenerated by a shorter process, and without
having been further split up, but of this, too, -there is no definite
ABSORPTION OF THE VARIOUS FOOD SUBSTANCES 451
proof. The regeneration, wherever it occurs, must presumably take
place in cells, and the only available cells in the digestive mucous
membrane are those which line the tube, or the leucocytes which
wander between them. Accordingly, both have been credited with
the power of absorbing (and perhaps transforming) these substances,
but the balance of evidence is in favour of the epithelial cells. We
cannot, however, as in the case of the fat, single out any particular
tract of epithelium as alone engaged in the absorption (and possibly
in the resynthesis) of the products of the digestion of the proteins.
In all likelihood the cells covering the villi are actively concerned,
but there is no valid reason for denying a share to the general lining
of the stomach and small intestine, even perhaps including the
Lieberkiihn's crypts or intestinal glands, which morphologically
form a kind of inverted villi. It is, indeed, true that the crypts
do not take part in the absorption of fat, for no granules blackened
by osmic acid occur in them during digestion of a fatty meal. But
this is a ground for attributing to them other absorptive functions
rather than for altogether denying to them a share in absorption,
unless, indeed, we assume that the secretion of the succus entericus
engrosses the whole activity of this extensive sheet of cells. Even
within physiological limits distension of the gut causes the crypts
to become shorter and broader, by a process of partial unfolding
which permits a greater part of their epithelium to come into con-
tact with the intestinal contents. In extreme distension they may
be completely smoothed out.
The extraordinary efficiency of the small intestine in digestion
and absorption is shown by the fact that, after removal of even
70 to 83 per cent, of the combined jejunum and ileum in dogs, the
metabolism is not necessarily much affected. On a diet poor in
fat the animals absorb as much of the fat as a normal dog, although
a smaller proportion when the diet is rich in fat. It has been
generally stated that it is never permissible to remove more than
one-third of the small intestine in man. But in one case 2f metres
was resected, or quite one-half, and the patient recovered. Even
the large intestine, which possesses Lieberkiihn's crypts, but no villi,
is able to absorb not only peptones and sugar, especially mono-
saccharides like dextrose, but also fats and native proteins. And
although these are powers which can be rarely exercised to any great
extent in normal digestion, they form the physiological basis of the
important method of treatment by nutrient enemata. The observa-
tion already mentioned (p. 331), that considerable quantities of
food administered by the rectum can pass through the ileo-colic
sphincter and valve into the lower part of the ileum, thanks to the
antiperistaltic movements of the large intestine, indicates that an
important part of the preliminary digestion and of the absorption
of enemata may occur in the small intestine. But remnants of the
452 ABSORPTION
proteolytic, amylolytic, fat-splitting, and inverting ferments which
have done their work in the small intestine are passed on into the
large, and may be demonstrated in its contents. Doubtless these
are able to act upon food substances which may have escaped com-
plete digestion and absorption in the higher parts of the alimentary
canal, as well as upon food substances injected into the rectum.
Summary. — With the proviso that in the case of the fats the
statement may in the present condition of our knowledge be some-
what ' diagrammatic,' we may sum up in a few words the chief
points in the absorption of the food materials. All the fats must be
split in order to be absorbed in soluble form from the intestine, but
need not be split in the lumen of the gut in order to be utilized by the
cells. For this reason they are to a great extent resynthesized to
neutral fat after absorption, and find their way into the blood, mainly
by way of the lymph, in particulate form. Proteins could perhaps to
a small extent be absorbed as such, but must be thoroughly hydrolysed
in order to be utilized by the tissues, and also in order to be freely
taken up from the gut. Carbo-hydrates in certain forms (mono-
saccharides) are capable without change of being both freely absorbed
from the intestine and thoroughly utilized by the cells ; only the more
complex carbo-hydrates need to be hydrolysed in order to be absorbed,
but all above the monosaccharides must be hydrolysed to monosac-
charides in order to be utilized. The substances which eventually
circulate in the blood in solution reach it through the gastro-intestinal
capillaries ; the substances which eventually circulate in the blood in
particulate form reach it through the lymphatics.
PRACTICAL EXERCISES ON CHAPTERS VI. AND VII.
i. Contraction of Isolated Intestines in Ringer's Solution. — Arrange
a good-sized water-bath (a water-tight garbage-can holding 20 litres
will do) so that the temperature of the water is kept at 37° to 38° C.
For this a gas regulator is most convenient, and also a stirring arrange-
ment worked by a small motor. But if neither of these is available,
a student, by a little care, can easily keep the water at the required
temperature by raising and lowering the gas flame and stirring occasion-
ally by hand. In the bath, support (a) a stock bottle of Ringer's
solution (footnote, p. 66), (b) a wide-mouthed bottle containing Ringer
for the reception of the stock of intestine, (c) a small cylinder for
segments of intestine whose contractions are to be recorded, (c) is
conveniently made in different sizes by cutting down glass T-pieces.
One which holds 4 or 5 c.c. is convenient. The bottom is plugged with
a rubber cork in which is fastened a hook. In the side-piece is fixed
by a rubber cork a glass tube ending in the cylinder in a narrow
orifice. This is connected with the oxygen-supply, conveniently ob-
tained under constant pressure from a small gas-container which is
periodically replenished from an oxygen cylinder. A separate oxygen
cylinder is connected with a tube passing to the bottom of (b) . A lever
with two arms is arranged on the same stand as (c), so that it can be
thrown on and off a slow-moving drum by a single movement of the stand .
All being ready, a rabbit is killed by being struck on the back of the
PRACTICAL EXERCISES 453
head. The small intestine is immediately removed. It may be cut
between double ligatures into several pieces for this purpose. The
contents are rapidly washed out by a stream of warm Ringer, and
the pieces placed in (b) , through which oxygen is kept bubbling. The
pieces are conveniently supported in the liquid by threads fixed by
the cork of the bottle. There is a hole in the cork for the escape of
the oxygen. The movements of the intestines in (&) can be studied
very well by inspection. Or a separate length of intestine maybe kept
for this purpose, the contents not being removed, but prevented from
escaping by ligatures at each end. This can be most easily observed in a
shallow dish of warm Ringer. Or a separate experiment can be made
in which the whole alimentary canal of a rabbit is carefully removed
and examined in oxygenated Ringer's solution.
A segment of intestine about 2 or 2^- cm. in length is now cut off
one of the pieces. A small ring of platinum or aluminium is tied to
a point on the circumference of one end of the preparation by a silk
thread passed through the wall. The other end is caught by a serve-
fine at a point exactly corresponding to the attachment of the ring, so
that the pull of the contracting longitudinal muscle should be in the
straight line joining these two points. The serve-fine has attached to
it a thread with a hook on the other end. In preparing the intestinal
segment it lies on a plate of glass above a vessel of warm water. The
small cylinder (c) is now partially filled with warm Ringer's solution.
The ring is grasped by fine forceps, and made to engage with the hook
at the bottom of the cylinder, care being taken not to injure the prepara-
tion in the process. The, cylinder is then fastened on its stand and
lowered into the bath. The thread is connected by its attached hook
to the lever, and oxygen allowed to bubble slowly and regularly through
the cylinder. Very soon rhythmical contractions begin (Fig. 173), and
continue for a long time. The effect on these contractions of abolish-
ing, reducing, or increasing the oxygen-supply may first be studied.
2. Effect of Blood-Serum on, the Contractions of Intestinal Segments.
— While a tracing is being taken as in i, fill a small bent pipette with
serum already warmed in the bath, pass the point of the pipette down to
the bottom of the cylinder without interfering with, the preparation, and
allow the serum to flow in till the Ringer's solution is displaced. Almost
at once the lever will begin to rise, indicating strong tonic contraction.
The increase of tone lasts for some time, but can soon be removed on
washingthe preparation with Ringer. This is most easily done, while the
drum is stopped, by introducing pipetteful after pipetteful of Ringer's
solution into the cylinder in the way described, allowing the liquid to
overflow into the bath. The subsequent addition of serum causes a
renewed increase of tone, and this may be many times repeated.
Determine the greatest dilution of the serum which still produces a
distinct effect upon the intestinal segment.
3. Action of Epinephrin (Adrenalin) on Intestinal Segments. — Pro-
ceed as in 2, but use various dilutions of adrenalin chloride instead of
serum. They must be freshly prepared. Instead of increase of tone,
inhibition of the movements and decrease of tone will be obtained
(Fig. 173).
This experiment may be performed at another stage in the course
(p. 720).
4. Quantitative Estimation of Ferment Action. — For pepsin an easy
method, although not a very accurate one, of estimating the rate at
which the fibrin disappears is to use fibrin stained with carmine. As
solution goes on, the dye colours the liquid more and more deeply, and
by comparing the depth of colour at any time with standard solutions
of carmine, we get the quantity of dye set free, and therefore of fibrin
454
DIGESTION AND ABSORPTION
digested. This method cannot be used for trypsin. A much better
method is that of Mett (p. 343). Fluid egg-white is sucked up into
fine glass tubes (of i to 2 mm. bore). The tubes are then heated in a
bath at 95° C. For use short pieces (i or 2 cm. long) are cut off and
placed in i or 2 c.c. of the liquid to be tested, the whole being kept at
38° to 40° C.
For amylolytic ferments where rapid work is required, glass tubes
filled with tinted starch paste may be used in the same way as the
Mett's tubes. A more accurate method, and yet a rapid and convenient
one, is based upon the time which is necessary in order that the iodine
reaction with starch may just disappear when a standard starch solution
is digested with a dilution
of the ferment solution
at 40° C.
5. Saliva — Collection
and Microscopic Examina-
tion of Saliva. — Chew a
piece of paraffin-wax, or
inhale ether or the vapour
of strong acetic acid . The
flow of saliva is in creased.
Collect it in a porcelain
capsule. Examine a drop
under the microscope. It
may contain a few flat
epithelial scales from the
mouth and a few round
granular bodies, the sali-
vary corpuscles, the gran-
ules in which often show
a lively, dancing move-
ment (Brownian motion) .
Filter the saliva to free it
from air-bubbles, and per-
form the following ex-
periments :
(a) Test the reaction
with litmus paper. It is
usually alkaline. An acid
reaction may indicate
that bacterial processes
are abnormally active in
Fig. 173. — Effect of Serum and Adrenalin on Con-
tractions of a Segment of Intestine. Rabbit's
intestine contracting in Ringer's solution. At
55 the Ringer's solution was replaced by dog's
serum, and this at 56 by adrenalin (1:5,000,000)
in serum. At 57 this weak adrenalin solution was
replaced by a stronger one (i: 500,000) in serum.
Time-trace, half-minutes. (Reduced to half.)
the mouth.
(6) Add dilute acetic acid. A precipitate indicates the presence of
mucin (p. 344). Filter.
(c) Add a drop or two of silver nitrate solution to the filtrate from
(b). A precipitate insoluble in nitric acid, soluble in ammonia, proves
that chlorides arc present.
(d) Add to another portion a few drops of dilute ferric chloride
slightly acidulated with dilute hydrochloric acid, and the same quantity
to as much distilled water in a control test-tube. A reddish coloration
is obtained, due to the presence of sulphocyanic acid, which is com-
bined with potassium and other bases in the saliva. The colour is dis-
charged by mercuric chloride. Or, a drop of saliva may be allowed to
fall from the mouth on a test-paper (prepared by soaking filter-paper
with a dilute starch solution, containing a little iodic acid, and allowing
it to dry in the air). The paper is coloured blue by the union of the
PRACTICAL EXERCISES 455
starch with iodine set free from the iodic acid by the action of the sulpho-
cyanic acid.
(e) Take some boiled starch mucilage, and test it for reducing sugar
by Trommer's test (p. 10). If no sugar is found, take three test-
tubes, label them A, B, C, and nearly half fill each with the boiled
starch. To A add a little saliva,* to B some saliva which has been
boiled, to C a little saliva which has been neutralized, and as much
0-4 per cent, hydrochloric acid as has been taken of the mucilage, so as
to make the strength of the acid in the mixture 0-2 per cent., a propor-
tion well below that of the gastric juice . Put the test-tubes into a water-
bath at 40° C. In a few minutes test the contents for reducing sugar.
Abundance will be found in A, none in B or C. In B the ferment
ptyalin has been destroyed by boiling; in C its action has been inhibited
by the acid. If the test-tubes have been left long enough in the bath,
no blue colour will be given by A on the addition of iodine, but a strong
blue colour by B and C—i.e., the starch will have completely disappeared
from A.
(/) Put some starch in a test-tube, add a little saliva, and hold in the
hand or place in a bath at 40° C. On a porcelain slab place several
separate drops of dilute iodine solution. With a glass rod add a drop
of the mixture in the test-tube to one of the drops of iodine at intervals
as digestion goes on. At first only the blue colour given by starch will
be seen; a little later a violet colour, due to the presence of erythro-
dextrin in addition to some unaltered starch. A little later the colour
will be reddish, the starch having disappeared and the erythrodextrin
reaction being no longer obscured. Later still no colour reaction will
be obtained, the erythrodextrin having undergone further changes, and
only sugar (maltose, isomaltose, and perhaps a trace of dextrose) and
achroodextrin — a kind of dextrin which gives no colour with iodine —
being present.
(g) Put two pieces of glass tube filled with tinted starch paste (p. 454)
into separate test-tubes. Cover one with 3 c.c. and the other with
6 c.c. of saliva. The saliva must all be taken from the same stock, and
must not be collected separately. Put in a bath at 38° C., and when a
fair amount of digestion has taken place in each, measure the length
of the column digested, and determine the relation between the amount
digested in the two tubes (p. 342).
(h) Dilute 2 c.c. of saliva with distilled water up to 20 c.c., and filter.
Take six test-tubes of the same width, and label them A, B, C, etc.
Measure into A 3 c.c. of the diluted saliva, into B 2 c.c., into C 1-3 c.c.,
intoDo'9C.c.,into Eo'6c.c., and into F 0-4 c.c. Thus a series is obtained
in which each tube contains (approximately) two-thirds as much ferment
as the one it follows. Add distilled water to tubes B to F, sufficient to
make up the volume in each to 3 c.c. Place the tubes in a beaker of
iced water; add to each 10 c.c. of a I per cent, solution of boiled starch
previously cooled in iced water, and shake so as to mix the contents.
Each tube now contains starch in uniform concentration, and ferment
in varying concentration. The low temperature prevents digestion till
all the tubes are ready. Now put the tubes simultaneously into a water-
bath at 40° C. for half an hour, and then back again into iced water
to prevent further digestion. Move them about in the iced water to
cool rapidly. Fill up the tubes with distilled water nearly to the top.
add a drop or two of iodine solution to each, and mix uniformly. The
tubes to which the smallest amounts of saliva were added will probably
* As it filters slowly, unriltered saliva may be used for Experiments (e),
-456
DIGESTION AND ABSORPTION
still show a distinct blue colour, while those at the other end of the
series will be brown or yellow, and the intermediate tubes bluish- violet.
Suppose D is the last tube still showing a bluish tint, then in the next
higher tube, C, all the starch has been hydrolysed at least to dextrin —
that is, 1-3 c.c. of the ten-times diluted saliva, or 0-13 of the original
saliva, has been sufficient to change all the starch in 10 c.c. of the i per
cent, solution. With another specimen of saliva the same result might
be reached in tube E, containing an amount of ferment equal to that
in 0-06 c.c. of the original saliva". We could then conclude that the
diastatic power of the second saliva was about twice as great as that
of the first. A closer approximation can now be made by setting up
two fresh tubes (C and E respectively for the two salivas) and deter-
mining the time required for the blue reaction with iodine to disappear,
taking out a drop from time to time and testing on a porcelain slab.
(«') Put a little distilled water into a porcelain capsule, and bring the
water to the boil. Now put into the mouth some boiled starch paste,
and move it about as in mastication. After half a minute spit the
starch out into the boiling water. Divide the water into two portions.
Test one for sugar, and the other for starch. Repeat the experiment,
but keep the starch two minutes in the mouth. Report the result.
(;') Starch solution to which saliva has been added is placed in a
dialyser tube of parchment-paper for twenty-four hours. At the end
of that time the dialysate (the surrounding water) should be tested for
sugar and for starch. Sugar will probably be found, but no starch.
If no reaction for sugar is obtained, the dialysate should be concen-
trated on the water-bath, and again tested.
6. Stimulation of the Chorda Tympani. — (i) Having previously
studied the anatomy of the mouth and submaxillary region in the dog
by dissecting a dead animal (Fig. 174), put a good -sized dog under
morphine. Set up an induction-machine- for a tetanizing current
(p- 200), and connect it with fine electrodes. Fasten the dog on the
holder, give ether if necessary, and insert a cannula in the trachea
(p. 202). Then make an incision 3 or 4 inches long through skin and
platysma muscle, along the inner border of the lower jaw, beginning
about the angle of the mouth, and continuing backwards towards the
angle of the jaw. Such branches of the jugular vein as come in the way
may be generally pushed aside, but if necessary they may be doubly
li gated and divided. Feel for the facial artery, so as to be able to
avoid it. Divide the digastric muscle about its anterior third, and
clear it carefully from its attachments; or, without dividing it, pull it
outwards with a hook. The broad, thin mylo-hyoid muscle will now
be seen with its motor nerve lying on it. Divide the muscle about its
middle at right angles to its fibres, and raise it carefully. The lingual
nerve will be seen emerging from under the ramus of the jaw. It runs
transversely towards the middle line, and then, bending on itself, passes
forwards parallel to the larger hypoglossal nerve. In its transverse
course the lingual will be seen to cross the ducts of the submaxillary
and sublingual glands. These structures having been identified, the
lingual nerve is to be ligatured before it enters the tongue and cut
peripherally to the ligature. Then a glass cannula of suitable size is to
be inserted into the submaxillary duct (the larger of the two), just as if
it were a bloodvessel (p. 63). A short piece of narrow rubber tubing
is carefully slipped on the end of the cannula. The lingual is now to be
lifted by means of the ligature, and traced back towards the jaw till its
chorda tympani branch is seen coming off and running backwards along
the duct. The chordo-lingual nerve (Fig. 160, p. 392) is then to be
cut centrally to the origin of the chorda tympani, which can now be
PRACTICAL EXERCISES
457
easily laid on electrodes by means of the ligature on the lingual. On
stimulating the chorda, the flow of saliva through the cannula will be
increased. The current need not be very strong. If the flow stops
after a short time, it can be again caused by renewed stimulation after
a brief rest. A quantity of saliva may thus be collected, and the experi-
ments already made with human saliva repeated.
(2) Expose the vago-sympathetic nerva in the neck on the same
side ; ligature it ; divide below the ligature ; and note the effect pro-
duced by stimulation of the upper end on the flow of saliva.
(3) Set up another induction-machine, and connect it with electrodes.
Stimulate the chorda, and note the rate of flow of the saliva. Then,
while the chorda is still being excited, stimulate the vago-sympathetic,
and observe the effect. If the experiment is successful, finish by
stimulating the chorda for a long time. Then harden both sub-
Digastric
Muscle (cut).
Hypoglossal
Nerve.
Mylo-hyoid Lingual Wharton's
Muscle (cut). Nerve. Duct.
Fig. 174. — Dissection for Stimulation of Chorda Tympani (after Bernard).
maxillary glands in absolute alcohol, make sections, stain with carmine,
and compare them.
7. Effect of Drugs on the Secretion of Saliva. — (i) Proceed as in
6 (i), but, in addition, insert a cannula into the femoral vein (p. 218).
On the cannula put a short piece of rubber tubing, filled with 0-9 per
cent, salt solution and closed by a small clamp, or a small piece of
glass rod, or a pair of bulldog forceps. While the chorda is being
stimulated inject into the vein 10 to 15 milligrammes of sulphate of
atropine by pushing the needle of a hypodermic syringe through 'the
rubber tube. This will stop the flow of saliva, and abolish the effect
of stimulation of the chorda. See whether the sympathetic is also
inactive, and report the result.
(2) Now empty the cannula in the submaxillary duct by means of a
feather, and fill it with a 2 per cent, solution of pilocarpine nitrate by
means of a fine pipette. Fill also the short rubber tube attached to
the cannula, and close it again. Compress the tube, and so force into
458 DIGESTION AND ABSORPTION
the duct a small quantity of the solution. Open the tube. Secretion
of saliva will again begin, and stimulation of the chorda will again cause
an increase in the flow. But after a few minutes the action of the
atropine will reassert itself, and the flow will stop. Renewed secretion
may be caused by a fresh injection of pilocarpine.
8. Gastric Juice — (a) Preparation of Artificial Gastric Juice. — Take
a portion of the pig's stomach provided, strip off the mucous membrane
(except that of the pyloric end, which is relatively poor in pepsin), cut
it into small pieces with scissors, and put it in a bottle with 100 times
its weight of 0-4 per cent, hydrochloric acid. Label and put in a bath
at 40° C. for three hours, and then in the cold for twelve hours. Then
filter.
(b) Take another portion of the mucous membrane, cut it into pieces,
and rub up with clean sand in a mortar. Then put it in a small bottle,
cover it with glycerin, label, and set aside for two or three days. The
glycerin extracts the pepsin.
(c) Take five test-tubes, A, B, C, D, E, and in each put a little washed
and boiled fibrin or a small cube of coagulated egg-white. To A add a
few drops of glycerin extract of pig's stomach, and fill up the test-tube
with 0-4 per cent, hydrochloric acid. To B add glycerin extract and
distilled water; to C glycerin extract and i per cent, sodium carbonate;
to D 0-4 per cent, hydrochloric acid alone; to E glycerin extract which
has been boiled, and 0-4 per cent, hydrochloric acid.
Put up another set of five test-tubes in the same way, except that a
few drops of a watery solution of a commercial pepsin are substituted
for the glycerin extract. Label the test-tubes A', B7, C', D', E'.
Into another test-tube put a little fibrin (or an egg-white cube), and
fill up with the filtered acid extract from (a). Label it F. Place all
the test-tubes in a tumbler, and set them in a water-bath at 40° C.
Put a piece of a Mett's tube (p. 343) into each of two test-tubes, and
add 15 c.c. of 0-4 per cent, hydrochloric acid. To one tube add 5 drops
and to the other 10 drops of the same filtered glycerin extract of gastric
mucous membrane. Put the tubes in the bath, and when digestion is
distinct at the ends of both tubes measure the length of the column
digested in each. What is the relation between the two (p. 342) ?
The experiment can be repeated with the hydrochloric acid extract of
the mucous membrane.
After a time the fibrin (or egg-white) will have almost completely dis-
appeared in A, A', and F, but not in the other test-tubes. Filter the
contents of A, A', and F into one dish.
(d) Test the filtrate for the products of gastric digestion :
(a) Neutralize a portion carefully with dilute sodium hydrox-
ide. A precipitate of acid -albumin may be thrown
down. Filter.
(jS) To a portion of the filtrate from (a) add excess of sodium
hydroxide and a drop or two of very dilute copper
sulphate. A rose colour indicates the presence of
proteoses or peptones. The cupric sulphate must be
very cautiously added, because an excess gives a violet
colour, and thus obscures the rose reaction. If still
mere cupric sulphate be added, blue cupric hydroxide
is thrown down, and nothing can be inferred as to the
presence or the nature of proteins in the liquid.
(y) Heat another portion of the filtrate from (a) to 30° C.,
and add crystals of ammonium sulphate to saturation.
A precipitate of proteoses (albumoses) may be ob-
tained. Filter off.
PRACTICAL EXERCISES
459
(6) Add to the filtrate from (y) a trace of cupric sulphate and
excess of sodium hydroxide. A rose colour indicates
that peptones are present. More sodium hydroxide
must be added than is sufficient to break up all the
ammonium sulphate, for the biuret reaction requires
the presence of free fixed alkali. A strong solution of
the sodium hydroxide should therefore be used, or the
stick caustic soda. The addition of ammonium sul-
phate will cause the red colour to disappear; so will the
addition of an acid. Sodium hydroxide will bring it
back. Ammonia does not affect the colour.
(e) To some milk in a test-tube add a drop or two of rennet extract,
and place in a bath at 40° C. In a short time the milk is curdled by
the rennin. (See p. 353 )
9. (i) To obtain Normal Chyme.— Inject subcutaneously into a dog,
one and a half hours after a meal of minced meat and water, 2 mg. of
apomorphine. Half of one of the ordinary tabloids is enough. Collect
the vomit.
(2) To obtain Pure Gastric Juice. — If the laboratory possesses a dog
with Pawlow's double cesophageal and gastric fistula, the juice may
be obtained in large amount by sham feeding with meat (p. 4°2)- I*
not, proceed as follows: Put a fasting dog under ether, and fasten on
the holder. Clip the hair and shave the skin in the middle line below
the sternum. Make a longitudinal incision
through the skin and subcutaneous tissue
from the xiphoid cartilage downwards for
3 or 4 inches. The linea alba will now be seen
as a white mesial streak. Open the abdomen
by an incision through it. Pull over the
stomach towards the right, and stitch it to
the abdominal wall, open it, and insert a
stomach cannula (Fig. 175). Make an incision
through the serosa and muscularis. Doubly
ligate and divide any vessels exposed in the
submucosa. Then make an opening in the mucosa of sufficient size to
just admit the gastric cannula. This will go into a smaller opening if it
is provided with a nick in the flange which enters the stomach. Be
careful to prevent blood from getting into the stomach. Immediately
stitch the wound in the stomach over the flange of the cannula, but
do not pass the stitches through to the internal surface of the mucosa.
Suture the muscles and skin separately. Then stitch up the wound in
the abdomen. Wash out any stomach contents with warm water. Put
a cork in the cannula, and cover the animal with a cloth. The follow-
ing experiments may now be performed: Expose both vagi in the neck.
Connect two pairs of electrodes with the secondary coil of an induc-
torium arranged for single shocks. By means of a key in the primary
stimulate the nerves with slow rhythmical induction shocks at the rate
of about one a second. Continue the stimulation for fifteen minutes,
collect any juice that may have been secreted, and apply the tests in (3).
If secretion is slow, a little distilled water may be put into the stomach,
and the vagus stimulation repeated. Mechanical stimulation of the
mucous membrane with a feather causes no secretion of acid gastric
juice, but may cause a secretion of alkaline mucus.
(3) (a) Test the reaction to litmus of the chyme obtained in (i), and
of the pure juice obtained in (2).
(b) Test their proteolytic powers by putting in a bath at 40° C. for
two hours two test-tubes containing respectively filtered chyme and
Fig. 175. — Stomach
Cannula.
46o
DIGESTION AND ABSORPTION
fibrin, and gastric juice and fibrin. The fibrin will be digested in both.
Estimate the proteolytic power quantitatively by Mett's tubes (p. 454).
(c) Add a few drops of the chyme and gastric juice to milk in two
test -tubes, and place them in a bath at 40° C. Repeat (c) after neutral-
izing the liquids.
(d) Examine a drop of the unfiltered chyme under the microscope.
Partially digested fragments of the food will be seen — muscular fibres
or fat cells. Filter, and proceed as in 8 (d) (p. 458).
(4) Test the filtrate from the chyme and the gastric juice for lactic
acid by Uffelmann's test or Hopkins 's test (p. 821), and for hydrochloric
acid by Gunzburg's reagent.
Uffelmann's Test for Lactic Acid. — The reagent is a dilute solution
of carbolic acid to which dilute ferric chloride has been added till the
colour is bluish (say a drop of a I per cent, ferric chloride solution to
5 c.c. of a i per cent, carbolic acid solution). The blue colour of the
mixture is turned yellow by lactic acid, but not by dilute hydrochloric
acid. Since Uffelmann's test is given also by phosphates, alcohol, and
sugar, which may sometimes be present in the stomach contents, it is
best to shake the gastric contents with ether, dissolve the ethereal
extract in water, and then make the test on the watery solution.
Gunzburg's Reagent for Free Hydrochloric Acid in Gastric Juice is
made by dissolving 2 parts of phloroglucinol and I part of vanillin in
30 parts by weight of absolute alcohol. A few drops of the reagent
are added to a few drops of the filtered gastric juice in a small porcelain
capsule, and the whole evaporated to dryness over a small bunsen
flame. If free hydrochloric acid is present, a carmine-red residue is
left. If all the hydrochloric acid is united to proteins in the stomach
contents, the reaction does not succeed. It is also hindered by the
presence of leucin.
10. Pancreatic Juice. — (a) Take a piece of the pancreas of an ox or
dog which has been kept twenty-four hours at the temperature of the
laboratory, and make a glycerin extract in the same way as in the
case of the pig's stomach in 8 (6). Put in a small bottle, and set aside
for a day or two.
(6) Put a little boiled fibrin into each of six test-tubes, A, B, C, D, E.
F. To A add a few drops of glycerin extract of pancreas, and fill up
with a i per cent, sodium carbonate solution ; to B add glycerin extract
and distilled water; to C glycerin extract and excess of 0^05 per cent,
hydrochloric acid ; to D i per cent, sodium carbonate alone ; to E i per
cent, sodium carbonate in which a few drops of glycerin extract of
pancreas have been previously boiled ; to F glycerin extract and excess
of 0-2 per cent, hydrochloric acid.*
Set up six test-tubes, A', B', C', D', E', F', in the same way, but
substitute a few drops of a solution of commercial pancreatin for the
glycerin extract. Set up two test-tubas as in expsriment 8 (p. 458)
with Mett's tubes. Put all the test-tubes in a tumbler, and place in a
bath at 40° C. The fibrin will be gradually eaten away in A and A1,
by the action of the trypsin, but will not swell up or become clear
before disappearing, as it does in dilute hydrochloric acid with glycerin
* With hydrochloric acid of different strengths the rapidity of digestion
of boiled fibrin by glycerin extract of dog's pancreas (i volume of extract
to 25 of acid) was found about the same for 0-3 and o'iy per cent, acid; much
less for o-o8 per cent., while in 0^04 per cent, acid there was practically no
digestion at all. In 0-4 per cent, acid digestion took place more rapidly than
in o-o8 per cent., but much less rapidly than in 0-17 per cent. In acid of all
strengths digestion was markedly slower than in i per cent, sodium car-
bonate.
PRACTICAL EXERCISES 46i
extract of stomach. Filter the contents of these test-tubes. Neutralize
the filtrate with dilute acid ; a precipitate will consist of alkali-albumin.
If such a precipitate is obtained, filter it off and test the filtrate for
proteoses and peptones as in 8 (d) (p. 458). Some digestion, and perhaps
a considerable amount, may also have taken place in F and F'; less
or none at all in C and C' ; and none in the other iest-tubes (pp. 359, 420).
(c) Add a few drops of the glycerin extract to a test-tube containing
starch mucilage, which has been previously found free from reducing
sugar. Put in a bath at 40° C. After a short time abundance of
reducing sugar will be found, owing to the action of the ferment,
amylopsin, or pancreatic amylase.
(rf) Mince thoroughly a good-sized piece of fresh pancreas, and shake
up well with three or four times its bulk of water. Put 5 c.c. of fresh
cream into a test-tube, then 10 c.c. of the extract, a few drops of chloro-
form to prevent the growth of bacteria, a few drops of litmus solution,
and if necessary enough of very dilute sodium hydroxide to just render
the colour distinctly blue. Shake up, and divide the mixture into two
portions, A and B. Boil one portion (B), and place the test-tubes at
40° C. Examine from time to time. The blue colour will disappear in
A, owing to the formation of fatty acids from the neutral fats, and
sodium hydroxide must be added to it to restore the colour. In B the
fat-splitting ferment has been destroyed by boiling, and fat-splitting
will not occur. Probably a distinct result will not be obtained for
several hours, and it will be best to leave the tubes in the incubator
overnight.
(e) If the laboratory possesses an animal with a pancreatic fistula,
the following experiment may be done by a limited number of students
with fresh pancreatic juice* collected from the fistula. Take five test-
tubes, A, B, C, D, E. Add 5 c.c. of pancreatic juice to each tube. Boil
E, and then cool it. Put into A and B small pieces of heat-coagulated
egg-white, into C a little starch mucilage, and into D and E 5 c.c. of
fresh cream. Add further to B a scraping of the mucous membrane of
the upper part of the small intestine which has first been washed free of
contents. To D and E add a drop or two of litmus solution, and, if
necessary, enough of dilute sodium hydroxide to just establish a blue
colour. Then put the test-tubes at 40° C., and examine after a time.
No digestion will have taken place in A, because the pancreatic juice, as
secreted, does not contain active trypsin. In B digestion may take
place, because the enterokinase in the intestinal mucous membrane
will activate the trypsinogen to trypsin. In C and D there will be
evidence of the production of reducing sugar and fatty acids respec-
tively, since the pancreatic juice, as secreted, contains active amylase
and steapsin. E will be unchanged unless by bacterial action.
(/) Leucin and Tyrosin. — As examples of amino-acids formed when
pancreatic digestion of proteins (fibrin or casein, e.g.) is allowed to go
on for some days.fleucin and tryosin maybe isolated. Add bromine-
water by drops to 5 c.c. of the digest; a pink colour indicates trypto-
phane. If the ' digest ' be neutralized, then filtered, and the filtrate
concentrated and allowed to stand, a crop of tyrosin crystals will
separate out, since tyrosin is only slightly soluble in watery solutions
of neutral salts. These crystals having been filtered off, the proteoses
(albumoses) and peptones can be precipitated together by alcohol, and
* A considerable flow of pancreatic juice can be obtained from a dog with
a pancreatic fistula by injecting intravenously an extract of intestinal mucous
membrane containing secretin (p. 407).
• | A little chloroform is added to prevent bacterial growth.
4&a DIGESTION AND ABSORPTION
afterwards separated, if that is desired, by redissolving the precipitate
in water and throwing down the proteoses by saturation with am-
monium sulphate. The alcoholic nitrate will contain any leucin that
may be present, since that body is moderately soluble in alcohol, as
well as traces of tyrosin, which, however, is much less soluble in this
medium. On concentration, crystals of both substances will be ob-
tained. Tyrosin crystallizes characteristically from animal liquids in
beautiful silky needles united into sheaves, leucin in the form of in-
distinct fatty-looking balls, often marked with radial striae and coloured
with pigment (Figs. 186 and 187, p. 488).
Tests for Tyrosin by M timer's Test. — Put a small quantity of tyrosin
into a test-tube. Add about 3 c.c. of the reagent,* and heat gradually
and gently to the boiling-point. A green colour is obtained.
II. Bile. — (a) Test the reaction of ox bile. It is alkaline to litmus.
(b) Add dilute acetic acid. A precipitate of bile-mucin (really
nucleo-albumin) falls down. Some of the bile-pigment is also pre-
cipitated. Filter. (Pig's bile contains more of the mucin-like sub-
stance than ox bile.)
(c) Put a little of the filtrate from (&) or of the original bile into a
porcelain capsule, add a drop or two of a dilute solution of cane-sugar,
and mix with the bile. Then add a few drops of strong sulphuric acid,
and stir; then a few drops more of the sulphuric acid, stirring all the
time. A purple colour appearing at once, or after gentle heating,
shows the presence of bile-acids (Pettenkofer's reaction). The bile
may be diluted before the addition of the sulphuric acid. In this case
a greater amount of the acid must be added. Examine the purple
liquid in a test-tube with a spectroscope (p. 74). Dilute the liquid with
water, adding some sulphuric acid to partially clear up the precipitate
caused by the water. Two absorption bands are seen, one to the red
side of D, and the other, a stronger and broader band, over and to the
right of E. When only a very small amount of bile-salts is present,
the reaction is made more sensitive if a solution of f urf uraldehyde (i to
i.ooo) is used instead of cane-sugar.
(d) Hay's Sulphur Test. — Sprinkle a little sulphur (in the form of
the fine powder known as flowers of sulphur) on the surface of some
bile in a small beaker or deep watch-glass. The sulphur will soon sink
to the bottom. Repeat with water; the sulphur will float. The
reaction is due to the diminution of the surface tension produced by
the bile -acids, and succeeds also in a solution of bile -salts. The test
is very sensitive. But in stomach contents, vomit, or stools, it rarely
gives good results, since alcohol or acetic acid is often present in the
gastric liquid, and phenol and its derivatives in intestinal contents,
and all of these cause such an alteration in the surface tension that the
sulphur sinks. Ether, chloroform, turpentine, benzine and its deriva-
tives, anilin and soaps, also vitiate the test in the same way.
(e) Add yellow nitric acid (containing nitrous acid) to a little bile on
a white porcelain slab. A play of colours, beginning with green and
running through blue to yellow and yellowish-brown, indicates the
presence of bile-pigment (Gmelin '^reaction). The reaction may also
be obtained by putting some yellow nitric acid into a test-tube, and
then running a little bile from a pipette on to the surface of the acid.
The play of colours is seen at the surface of contact. Where the bile-
pigment is present only in traces, some of the liquid may be filtered
* The reagent for this test is prepared by mixing thoroughly i volume of
formalin, 45 volumes of distilled water, and 55 volumes of concentrated
sulphuric acid.
PRACTICAL EXERCISES 463
through white filter-paper, and the test applied by putting a drop of
the nitric acid on the paper.
(/) Cholesterin or Cholesterol (Fig. 176) — Preparation. — Extract a
powdered gall-stone (preferably a white one) with hot alcohol and ether
in a test-tube. Heat the test-tube in warm water, not in the free flame.
Put a drop of the extract on a slide. Flat crystals of cholesterin, often
chipped at the corners, separate out. (a) Carefully allow a drop of
strong sulphuric acid and a drop of dilute iodine to fun under the cover-
glass. A play of colours — violet, blue, green, red — is seen.
($) Evaporate a drop of the solution of cholesterin. in a small porce-
lain capsule, add a drop of strong nitric acid, and heat gently over a
flame. A yellow stain is left, which becomes red when a drop of am-
monia is poured on it while it is still warm.
(7) Dissolve a little cholesterin in chloroform. . Add an equal bulk
of strong sulphuric acid, and shake gently. The solution turns red
and the subjacent acid shows a green fluorescence.
(S) Put a drop or two of water in a watch-glass, and add a drop of an
ethereal solution of cholesterin. The cholesterin is precipitated, and
will not dissolve in the water even on heating. Repeat the observation
with bile instead of water. The cholesterin dissolves in the bile.
(g) To a little of the filtrate from a
peptic digest (e.g., fibrin which has been
digested for twenty-four hours with
pepsin and hydrochloric acid) add some
bile. A precipitate is thrown down,
which is redissolved in excess of the
bile (p. 370).
(h) Shake up a little bile with some
rancid olive -oil in a test-tube. An emul-
sion is formed. Repeat the experiment
with the same quantities of bile and oil,
but use perfectly fresh oil. Compare the
stability of the two emulsions, allowing
the tubes to stand together for a while. Fig. 176. — Crystals of Cholesterin
(i) To some starch mucilage, shown (Frey).
to be free from sugar, add a little bile,
and place in a bath at 40° C. After a time test for reducing sugar.
Report the result. Bile often has a slight diastatic power.
(/) To demonstrate the Presence of Iron in the Liver Cells. — Steep sec-
tions of liver in a solution of potassium ferrocyanide, and then in dilute
hydrochloric acid. Or a 1-5 per cent, solution of potassium ferrocyanide
in 0-5 per cent, hydrochloric acid may be used. (The iron may pre-
viously be fixed in the tissue by hardening it in a mixture of alcohol
and ammonium sulphide.) The sections become bluish from the
formation of Prussian blue. A fine-pointed glass rod or a platinum
lifter should be used in manipulating them. A steel needle cannot be
employed. Mount in glycerin or Farrant's solution, or (after dehy-
drating with alcohol and clearing in xylol) in xylol-balsam. Blue
granules may be seen under the microscope in some of the hepatic cells.
Sections of spleen may also be examined for this reaction.
12. Microscopical Examination of Faeces. — Examine under the micro-
scope the slides provided. Draw, and as far as possible determine the
nature of, the objects seen (p. 424).
13. Absorption of Fat. — (a) Feed a rat or frog with fatty food; kill
the rat in three or four hours, the frog in two or three days. Imme-
diately after killing the rat open the abdomen, carefully draw out a
loop of intestine, and look through the thin mesentery. The white
464 DIGESTION AND ABSORPTION
lacteals will probably be seen ramifying in the mesentery. They
appear white on account of the presence of globules of fat in the chyle
with which they are filled. Strip off tiny pieces of the mucous mem-
brane of the small intestine, and steep them in \ per cent, solution of
osmic acid for forty-eight hours. Then tease fragments of the mucous
membrane in glycerin and examine under the microscope. To preserve
the specimens take off the glycerin with blotting-paper and mount in
Farrant's medium, which is a preservative glycerin mixture. Other
portions of the mucous membrane may be hardened for a fortnight in
a mixture of 2 parts of Miiller's fluid and i part of a i per cent, solution
of osmic acid. Sections are then maae with a freezing microtome after
embedding in gum. No process must be used by which the fat would
be dissolved out (Schafer). (See Fig. 172, p. 441.)
(6) Feed a cat with 30 grammes of butter stained a deep red with the
dye Sudan III. After five hours anaesthetize the animal with ether,
insert a cannula in the carotid artery, and obtain a sample of blood.
Defibrinate the blood, and separate the serum by the centrifuge. If
digestion and absorption of the fat have proceeded normally, the
serum will contain numerous fat droplets, and will be tinged pink by
the dye, which can be dissolved out of it by shaking up with ether. On
opening the abdomen it will be seen that the mucous membrane of the
small intestine, as far down as the fat has reached, is stained pink, and
that the lacteals in the mesentery are also pink. Observe whether any
of the pigment has passed into the urine.
14.* Time required for Digestion and Absorption of Various Food
Substances. — Feed three dogs, A, B, and C, which have previously fasted
for twenty-four hours, with a meal containing starch (proved to be free
from sugar), lard, and meat.
(1) After fifteen minutes inject subcutaneously into A 2 c.c. of a
o-i per cent, solution of apomorphine. Note the time which elapses
before the animal vomits. Collect the vomit.
(a) Examine a little of it under the microscope, and make out fat
globules, muscular fibres and starch granules. The latter can be recog-
nized by their being coloured blue by a drop or two of iodine solution.
(b) Filter the chyme, mixing it, if necessary, with a little water, and
test it as in 8 (d) (p. 458) for the products of digestion of proteins. In
addition, test for starch, dextrin, and reducing sugar.
(2) One and a quarter hours after the meal inject apomorphine into
dog B, and proceed as in (i).
(3) Two and a half hours after the meal inject apomorphine into
dog C, and proceed as in (i). Compare the results from the three
specimens of chyme.
15.* Quantity of Cane-Sugar inverted and absorbed in a Given Time. —
Take three dogs, A, B, and C, which have fasted for twenty-four hours.
The animals should be about the same size. Feed A and B with
100 c.c. of a standard solution of cane-sugar (about a 20 per cent, solu-
tion), or as much more as they will take. If the dogs have been kept
without water for a day they will more readily take the sugar solution.
Or it may be given through a tube passed into the stomach, and in
this case a larger quantity of sugar can be given. A gag consisting of
a piece of wood with a hole in the middle of it, through which the tube
is passed, must first be secured in the dog's mouth. Feed C with
* Experiments 14 and 15 are conveniently done in a class by assigning
each of the three animals to a separate set of students. The contents of the
stomach and intestine are divided into three portions, so that each set has
a sample from each dog.
PRACTICAL EXERCISES 465
50 grammes of powdered cane-sugar mixed with lard, the mixture being
rolled into little balls.
(1) After a quarter of an hour put A under chloroform or the A.C.E.
mixture, and fasten it on a holder. Kill the animal with chloroform,
open the abdomen, tie the oesophagus, place double ligatures on the
pyloric end of the stomach and the lower end of the small intestine, and
divide between them. Cut out the stomach and intestine ; wash their
contents into separate vessels, and test the reaction with litmus paper.
Add water and rub up thoroughly. Filter. Wash the residue re-
peatedly with small quantities of water, and pass all the washings
through the filter. Make up each of the two nitrates to 200 c.c.
(a) Test the filtrates from the contents of the stomach and intes-
tines qualitatively for dextrose by Trommer's (p. 10) or Fehling's
(p. 526) and the phenyl-hydrazine test (p. 525).
(b) If no reducing sugar is present, add to 20 c.c. of each filtrate I c.c.
of hydrochloric acid, boil for half an hour, and again test for reducing
sugar. If it is now found, some cane-sugar is present.
(c) If reducing sugar is found, estimate its amount as dextrose by
Fehling's solution (p. 527) in a measured quantity of the original
filtrate of the gastric or intestinal contents before and after boiling
with one-twentieth of its volume of hydrochloric acid.
(d) Estimate in the same way the amount (as dextrose) of the invert
sugar in the standard solution of cane-sugar after inversion, and before
inversion if it gives the qualitative test for reducing sugar before it has
been boiled with acid.
From the data obtained (and taking 95 parts of cane-sugar as equal
to 100 parts of dextrose) calculate the amount of cane-sugar absorbed,
left unchanged, and inverted, though not absorbed.
(2) One and a half hours after the meal anaesthetize B, and proceed
as in (i).
(3) Two hours after the meal proceed in the same way with C. But
in addition observe the lacteals in the mesentery, by gently lifting up
a loop of intestine immediately after opening the abdomen. If the
absorption of the fat has begun, they will be easily visible, as a network
of fine milk-white vessels. Also examine the gastric and intestinal
contents with the microscope for fat globules. Compare your results
on the amount of sugar obtained from the three animals. Probably
much more unabsorbed sugar will be found in C than in B, as the lard
hinders it from being dissolved.
16. Auto-Digestion of the Stomach. — In some of the previous experi-
ments the stomach of an animal killed during digestion should be
removed from the body after double ligation of oesophagus and duo-
denum, and placed in a water-bath at 40° C. After several hours the
contents should be washed out and the mucous membrane examined.
It may be entirely eaten away in parts.
FORMATION OF LYMPH
Different Kinds of Lymph. — -We ought to distinguish the lymph
as we collect it from the great lymphatic trunks, not only from the
liquids of the serous cavities, but still more sharply from the liquid
which fills the multitudinous clefts and spaces of the tissues. It is
now pretty definitely established that the tissue spaces do not com-
municate by actual passages with the lymphatic vessels, but that
the latter form everywhere a closed system like the blood- vascular
system, the lymph capillaries merely lying in the tissue spaces
(Sabin, etc.). This conception entails a radical change in the
current views of lymph production. If the lymphatics form a
closed system, the lymph cannot be actual tissue fluid, but only
tissue fluid modified by its passage through the walls of the lymph
capillaries, just as tissue fluid is not actual blood-plasma, but plasma
modified by its passage through the walls of the blood capillaries
as well as by exchange with the tissue elements.
Although it is customary to speak of the lymph obtained from
the lymphatic vessels as if it were perfectly homogeneous, there is
no experimental ground for supposing that the lymph from different
tracts, or the tissue liquid in contact with the cells of different
organs, or even the tissue liquid in contact with one and the same
cell at different parts of its periphery, has a uniform composition,
or even a uniform molecular concentration. There are, indeed,
certain general considerations which show that this cannot be so.
Still less can it be assumed that the serous cavities, although they
come into relation with lymphatics and bloodvessels in their walls,
are analogous to colossal tissue spaces or even to expansions of the
closed lymphatic system, or that the liquids contained in them,
normally in scant amount, are simply tissue, or if not tissue, then
simply lymphatic lymph. The cerebrospinal fluid, which bathes
the external surface of the central nervous system and fills its
cavities, and the special liquids of the eyeball — the aqueous humour
and the liquid of the vitreous humour — although no doubt, in
addition to their other functions, they may in some degree minister
to the nutrition of the tissues with which they are in contact, are
466
FACTORS CONCERNED IN LYMPH FORMATION 467
as regards their composition and mode of formation scarcely more
closely allied to lymph than sweat is. They are almost free from
protein, and are secreted by special structures — the choroid plexus
and the uveal epithelium — quite different from any that can be
concerned in the formation of ordinary lymph.
It is very true these liquids are not blood, but that is scarcely a
sufficient reason for calling them lymph, else we might classify
sweat or even milk as lymph also. If a term is desirable to indicate
that they have certain relations with lymph, they might perhaps
be spoken of as lymphoid secretions. It may be that the essential
difference in the chemical composition of these lymphoid secretions
and lymph — the practical absence of protein — is related to the
difference in the manner of their formation. The uveal and choroidal
epithelial cells, interposing the depth of their columns or cubes
between the blood and the free surface at which the liquid escapes,
may well be suited to hinder the passage of the protein molecules
which find their way with greater ease through the thin endothelium
of the capillary wall into the tissue spaces, and from these into the
lumen of the closed lymphatics (see p. 439)- Nevertheless, we shall
recognize later on in the glomeruli of the kidney an instance of
blood capillaries but little pervious to proteins, and there are several
other facts which show that the capillaries may differ considerably
in different organs in the readiness with which they permit the
various constituents of the plasma to pass through their walls.
Further, in discussing the mechanism by which lymph is formed,
we shall see reason to doubt whether mechanical filtration, due to
differences of hydrostatic pressure on the two surfaces of the
capillary endothelium, has much, if anything, to do with the
passage either of protein or of the other constituents of the lymph
from the lumen of the capillaries into the tissue spaces. At first
glance, indeed, such a process would seem to be admirably fitted to
explain the fact that, while lymph differs but little from blood-
plasma in the proportions of its other constituents, it is at most no
more than half as rich in protein. For there are many filters which
allow substances in ordinary solution and their solvent to pass
through without alteration in their relative proportions, while
substances like proteins in colloid solution are kept back to a
greater or less extent.
Factors concerned in Lymph Formation. — The teaching of Ludwig,
that lymph is formed by the filtration, and in a minor degree by the
diffusion, of the constituents of blood- plasma through the walls of the
capillaries into the tissue spaces, was based en such facts as the
increase in the tissue liquid of a limb or organ which occurs when
the exit of blood from it by the veins is hindered, or when the
quantity of the circulating liquid is increased by the injection of
blood or salt solution. It was first seriously called in question by
468 FORMATION OF LYMPH
Heidenhain, who advanced the theory that lymph is secreted by
the endothelium of the blood capillaries. One of Heidenhain's
strongest arguments in favour of his secretion theory was the
existence of substances which, when injected into the blood, in-
creased the flow of lymph from the thoracic duct of the dog without
affecting appreciably the arterial pressure. He divided these so-
called lymphagogues into two classes: (i) Substances like peptone,
extracts of the head and liver of the leech, extract of crayfish
muscle, egg-albumin, etc., which cause not only an increase in the
rate of flow, but an increase in the specific gravity and total solids
of the lymph; (2) crystalloid substances, like sugar, salt, etc., which
cause an increased flow of lymph more watery than normal.
Starling has shov.n that, although the lymphagogues of the second
class do not raise the arterial pressure, they do, by attracting water
from the tissues and thus causing hydraemic plethora (an excess of
blood of low specific gravity), bring about a marked rise of venous,
and therefore, what is the important thing for lymph filtration, of
capillary pressure. But it can be demonstrated that vaso-dilala-
tion with increase of capillary pressure is not in itself sufficient to
increase the formation of lymph. We have seen, e.g. (p. 179), that
when the chorda tympani nerve is stimulated in the dog the arteri-
oles of the submaxillary gland are dilated, and no doubt the pres-
sure in the capillaries is increased. No increased flow of lymph,
however, takes place from the submaxillary lymphatics during even
prolonged excitation of the chorda, nor do the lymph spaces of the
gland become distended (Heidenhain). In the horse also the spon-
taneous flow of lymph from the quiescent parotid is not appreciably
altered by excitation of the secretory nerves of the gland or by
pilocarpine (Carlson). There is every reason to believe that during
active secretion of saliva tissue liquid is really formed from the
blood in increased amount, and that it is from the tissue spaces
that the gland-cells directly obtain the increased supply of water
and other substances necessary to sustain the increased secretion.
But a balance is maintained between the production of tissue liquid
and its removal by the gland-cells. When the gland is quiescent,
the small amount of tissue liquid normally formed from the blood
capillaries for the nutrition of the cells is balanced by, upon the
whole, an equal amount of lymph secreted from the tissue spaces
into the lymph capillaries.
We may say, indeed, that the closed lymphatic system has for
its great function the regulation of the quantity and quality of the
tissue liquid. In glands with an external secretion increased irriga-
tion of the tissue spaces from the blood does not as a rule lead to
increased flow of lymph, because the surplus fluid is required to
form the secretion. In other organs, however, such as the muscles
and the ductless glands, it is probable that the augmented irriga-
FACTORS CONCERNED IN LYMPH FORMATION 469
tion rendered necessary by functional activity is always associated
with an accelerated flow of lymph, which carries off the surplus
liquid, including a portion of the waste products. It is probable
that an important factor in the production of oedema may be the
derangement of the mechanism, whatever it is, through which the
adjustment of the rate of formation of tissue liquid to that of
lymphatic lymph is achieved. But it must be remembered that in
all the organs the blood capillaries not only supply materials to the
tissue spaces, but take up materials from them. Indeed, there are
facts which indicate that in general water and dissolved substances
pass more easily and in greater amount back from the tissues into
the blood than into the lymphatics. So that, while the lymphatics
constitute an accessory drainage system, the bloodvessels irrigate
the tissues and drain them as well. A consequence of this, as well
as of the great difference in the capacity of the different tissues for
storing water, is that the amount of tissue lymph formed can never
be estimated from the amount of lymphatic lymph leaving an organ.
Thus the flow of lymph from the limbs at rest is very small in com-
parison with the flow from the abdominal viscera, which constitutes
the great bulk of the lymph passing along the thoracic duct. This,
however, does not prove that very little liquid passes out of the
limb capillaries, for"the chief tissue of the limbs, the muscles, pos-
sesses a far greater storage capacity for water than the intestines and
digestive glands. In the one case we have a field whose soil takes
up a great deal of water and is not easily saturated; in the other a
field whose soil soon becomes water-logged and refuses to take up
any more. With the same supply from the irrigating ditch, little
or no water may drain off at the foot of the first field, a great deal
at the foot of the second.
Where the main lymphatics are themselves blocked by mechanical
pressure or by inclusion in a ligature, the balance is, of course,
grossly upset by the failure of the outflow of lymph to keep pace
with its formation. Where an obstruction on the course of the
veins is responsible for the oedema, the lymphatic outflow, to be
sure, is not directly interfered with. But the nutrition and the
respiration of the vascular walls themselves, including the endo-
thelium of the capillaries, necessarily suffers from the insufficiency
of the blood- flow, and the crippled capillaries may very well become
abnormally permeable for water, salts, and the other constituents
of lymph. And while ordinary mechanical filtration may not be a
factor, or a very unimportant one, in the passage of liquid through
the normal capillary wall, it may become far more effective when
it acts on a damaged wall. The tissue cells also suffer from lack
of oxygen and nutritive material, and from the accumulation of
waste products, including acid substances, which cause them to
take up and to hold more water than normal. Even in the absence
47° FORMATION OF LYMPH
of changes in the mechanical conditions of the blood and lymph
circulations, alterations in the tissues must be recognized as among
the causes of oedema (Fischer). Thus it is clear that the interpre-
tation of such an apparently simple experiment as the production
of oedema by the ligation of a vein needs great care. Whatever it
proves, it may be said with confidence that it does not prove that
the increased capillary pressure is the direct cause of the oedema.
A mere increase in the capillary blood-pressure does not of itself
accelerate the formation of tissue liquid from the blood any more
than that of lymph from the tissue liquid, as is shown by the fact
that, when the chorda tympani is stimulated after injection of a
dose of atropine sufficient to prevent all salivary secretion, there is
neither oedema of the gland nor increase in the flow of lymph from
it, although the arterioles are as widely dilated as before. When the
blood-pressure is greatly increased in the anterior portion of an
animal by clamping the aorta, or in the whole animal by continued
stimulation of the cut medulla oblongata or the splanchnic nerves,
the blood does not alter in concentration in the least, showing that
no sensible increase in the passage of water into the lymph has
occurred. After division or embolism of the medulla oblon-
gata, and consequent paralysis of the vaso-motor centre and
general vascular dilatation, it is stated that the injection of sodium
chloride produces an increase in the lymph-flow as great and as
durable as in the normal animal, and which can continue even after
death (Pugliese). The action of the first class of lymphagogues,
which cannot be explained as the consequence of an increase of
capillary pressure, because the pressure in the capillaries is not
consistently increased, and may even in the case of some of these
lymphagogues be diminished, is attributed by Starling to an injurious
effect on the capillary endothelium (and especially on the endo-
thelium of the capillaries of the liver, since nearly the whole of the
increased lymph-flow comes from that organ), which increases its
permeability. But it is not easy to distinguish an increase of per-
meability produced by lymphagogues from an increase of secretory
activity of the endothelial cells.
Hamburger, too, has brought forward results which it is difficult
to reconcile with a theory of filtration even for the second class of
lymphagogues. Further, Heidenhain has shown that some time
after injection of a crystalloid substance, like sugar, into the blood,
a greater percentage of the substance may be found in the lymph
than in the blood. Now, when a mixture of crystalloids and col-
loids is filtered through a thin membrane, the percentage of crystal-
loids in the filtrate is never, at most, greater than in the original
liquid. And although Cohnstein states that, if time enough be
allowed, the maximum concentration of sodium chloride in the
lymph, after intravenous injection, becomes approximately the
FACTORS CONCERNED IN LYMPH FORMATION 47*
same as the maximum in the blood, this fact loses its weight as
an argument in favour of the filtration hypothesis when we re-
member that, according to Asher, all the solids of the lymph are
markedly increased when even small quantities of crystalloids are
injected into the veins. Upon the whole, then, it may be con-
cluded that up to the present it has not been shown that filtration
due to the excess of pressure in the capillaries over that in the
lymph spaces is an effective factor in the formation of lymph. Nor
is it at all easier to explain lymph formation as a matter of pure
osmosis or diffusion. Lazarus-Barlow found, for example, that in
the great majority of his experiments the injection of a concen-
trated solution of sodium chloride, dextrose or urea into a vein was
followed, not by an initial diminution in the outflow of lymph (as
might have been expected if the exchange of water between the
blood and the tissue spaces, and between the tissue spaces and the
lymph capillaries, was regulated solely by differences in osmotic
pressure), but by an immediate increase. And Carlson has shown
that the osmotic pressure of lymph coming from the active salivary
glands, as measured by the freezing-point method, may, under
chloroform or ether anaesthesia, be distinctly less than that of the
blood-serum. Water must therefore be passing from a liquid of
higher to one of lower osmotic concentration.
Nevertheless, it would be erroneous to assume that because
osmosis and diffusion have not been shown to satisfactorily account
for all the phenomena of lymph formation, they exert no influence
upon it. It is probable, indeed, that their action is fully as im-
portant as in absorption from the alimentary canal, although, as in
absorption, it is often overlaid and always modified by the specific
permeability of the blood-capillary walls, the lymph-capillary walls,
and the tissue cells in general, in virtue of which they exert an
action upon the quantity and composition of the lymph analogous
to the action exerted in a higher degree by the cells of the digestive
glands upon the quantity and composition of the liquids passing
into their ducts.
It is not difficult to illustrate the fact that phenomena of osmosis and
diffusion emerge, although not of course in such purity as in physical
experiments, when we study the interchange between the blood and
the tissue liquids. If, for example, a hypertonic solution of sodium
chloride is injected into the blood, water rapidly passes from the tissues
to the blood as it would through a semipermeable membrane, and the
blood becomes diluted. At the same time sodium chloride leaves the
blood and passes into the tissues, as it would do by diffusion from a
place of higher to a place of lower concentration. But after this has
gone on for some time, and the concentration of the blood in salt has
sunk, it may be, to that in the lymph, salt still continues to pass out
of the blood, and the excess of water also leaves the bloodvessels till the
osmotic pressure of the blood has again become normal. When isotonic
and even hypotonic solutions of sodium chloride are injected, salt also
472 FORMATION OF LYMPH
leaves the blood and enters the lymph, although it ought not to do so
by diffusion, while water, which might pass from the hypotonic blood
into the lymph by osmosis, moves in the same direction from the blood
to which the isotonic salt solution has been added. Regulative mechan-
isms, in short, exist which tend, with, but also without, the co-opera-
tion of diffusion and osmosis, and even, so to say, in their teeth,
to bring back the quantitative and qualitative composition of the
blood to the normal. Exactly similar phenomena are witnessed when
the equilibrium is upset from the other side by the injection of salt
solutions into the subcutaneous tissue or the intramuscular connective
tissue. Hypotonic sodium chloride solution injected into the sub-
conjunctival connective tissue quickly loses water and gains sodium
chloride, as it ought to do if under the influence of osmosis and diffusion,
and hypertonic salt solutions gain water. But eventually hypertonic,
hypotonic, and isotonic solutions, and even serum itself, are completely
absorbed, which could not occur in the presence of diffusion and
osmosis alone. Sometimes in dropsy it appears that the oedema liquid
is absorbed when the patient is put on a diet free as far as possible
from salts. The suggestion is that the regulative mechanism which
tends to keep the molecular concentration of the blood and lymph
approximately constant provides that as the salt content of the body
falls, which it does through continued excretion of salts in the urine,
water is eliminated in corresponding amount.
The Contribution of the Tissue-Cells to the Lymph. — So far we
have considered the passage of the lymph constituents, on the one
hand through the endothelium of the blood capillaries into the
tissue spaces ; on the other, from the tissue spaces through the endo-
thelium of the lymph capillaries. But it is not to be supposed that
the liquid lying in clefts, partly bounded by blood capillaries, partly
by lymph capillaries, partly by tissue-cells, should be affected solely
by the first two. The third anatomical element must contribute
something to, or withdraw something from, the tissue liquid, and
may thus play a part in the formation of lymph from the latter.
The recent researches of Asher and his pupils have raised the ques-
tion of the relation between the physiological activity of the organs,
and especially of the glands, and the formation of the lymph. They
conclude that the common doctrine that lymph is simply a diluted
blood-plasma is erroneous. Lymph*, they say, far from being a
mere nitrate or even a secretion from the blood, is formed by the
activity of the organs, and may actually be absorbed by the blood
from the tissue spaces. In fact, according to their view, the in-
travenous injection of lymphagogues, both crystalloid and colloid,
only causes an increased flow of lymph in so far as it leads to in-
creased glandular secretion. But this generalization has had only
a short-lived vogue, and one by one some of the main results which
seemed to support it have been disproved or shown to be capable
of interpretation in a different sense. For example, it was stated
that secretin causes a flow of lymph from the lymphatics of the
pancreas, as well as a flow of pancreatic juice. But it has been
shown that the increased production of lymph is not due to the
INFLUENCE OP NERVES ON LYMPH FORMATION 473
secretin at all, but to lymphagogue substances, including proteose,
extracted with the secretin from the intestinal mucous membrane.
A solution of secretin can be prepared which causes a considerable
increase in the secretion of pancreatic juice and bile, but no augmen-
tation whatever in the flow of lymph from the thoracic duct.
Again, it was asserted that peptone, a noted lymphagogue, produces
a great increase in the biliary secretion. It has been demonstrated,
however, that the action of the peptone is merely to cause expul-
sion of the contents of the gall-bladder by the mechanical effect of
the swelling of the liver, and not at all to stimulate the liver-cells
to form more bile. For it produces no effect on the flow of bile
if the gall-bladder be emptied or the cystic duct tied before the
injection (Ellinger). That active salivary secretion is not accom-
panied by increased lymph-flow from the lymphatics of the salivary
glands has been mentioned above. Nevertheless, we may safely
assume that the activity of the organs does make a contribution to
the lymph — to its solids, if not in any important degree to its water-
content, although to say that they alone are concerned in its forma-
tion, to the exclusion of the capillaries, is altogether an over-state-
ment. The waste-products of the tissues pass into the lymph, and
possibly, as Koranyi suggests, may, by increasing its molecular
concentration, cause the passage of some water into it from the
blood. Or the decomposition of the large protein molecules, which
in tissue metabolism are breaking down into numerous smaller
molecules, may entail an increase of osmotic pressure in the cells
themselves, which in turn may lead to withdrawal of water by the
cells from the tissue liquid. The osmotic pressure of the liquid
may thus rise, and water may pass into the tissue spaces from the
blood. The molecular concentration of lymph (except in anaesthe-
tized animals as mentioned above) is in general somewhat greater
than that of blood- serum — e.g., in one observation A of serum
was 0-605° C., and of lymph 0-610° C. For the solid tissues, the
freezing-point of which, however, cannot be as satisfactorily deter-
mined as that of liquids, the following values of A were obtained :
Brain, 0-65°; muscle, 0-68°; kidney, 0-94°; liver, 0-97°; while for
blood it was 0-57° (Sabbatani).
To sum up, we may say that while the physical processes of filtra-
tion, osmosis and diffusion may play a part in the passage of water
and solids through the walls of the blood capillaries, as well as from
the tissue-cells into the tissue spaces, and from these spaces into the
lymph capillaries, there is much which they leave unexplained, and
which at present, for the want of a more precise term, we must attribute
to secretory activity.
Influence of Nerves on Lymph Formation. — In one instance
it appears to have been shown that lymph may be formed
under the influence of secretory nerves. In the males of certain
474 FORMATION OF LYMPH
aquatic birds erection is due to the filling of the corpus cavernosum.
not with blood, but with lymph. The lymph is secreted rapidly by
the so-called bodies of Tannenberg when certain sympathetic nerve-
fibres are experimentally stimulated, and passes into the corpus
cavernosum, which swells up. If a small incision is made in the
corpus, a large quantity of clear lymph, which clots slowly on stand-
ing, escapes. There is a simultaneous vasodilatation. After erection,
the lymph is rapidly and completely reabsorbed (Eckhard, Muller).
Although no definite lymph-secretory nerve-fibres have as yet
been discovered in mammals and for ordinary tissues, it is possible
that they exist (Sihler). As already pointed out, the same volume
of liquid as escapes into the ducts of the active submaxillary gland
must, upon the whole, pass out of the blood capillaries. On what
principle shall we distinguish one only of these processes as physio-
logical secretion ? They begin together when the chorda tympani
is stimulated. A drug which paralyzes secretory nerve-endings
abolishes both effects. The simplest explanation is that the chorda
contains secretory fibres which influence the formation both of
saliva and of the tissue liquid from which it is recruited; and, so
far as this consideration goes, it is just as logical to consider the
increase in the supply of tissue liquid as the cause of the increase
in the flow of saliva as to consider the increased salivary secretion
as the cause of the increased flow of liquid into the tissue spaces.
The increased flow of liquid may be brought about either by an
action of the nerve on the gland-cells, causing them to produce a
hormone, which then effects the blood capillaries (Carlson), or by
a direct action on the capillary endot helium. The advantage to
cells engaged in the active secretion of saliva of being immersed in
an abundant bath of tissue liquid is obvious.
The post-mortem flow of lymph, which may continue in some
cases long after complete cessation of the circulation — for an hour
after injection of dextrose to produce hydrsemic plethora; for as
much as four hours after injection of extract of the strawberry,
which is a lymphagogue of Heidenhain's first group (Mendel and
Hooker) — is a phenomenon whose relation to normal lymph forma-
tion has not been definitely settled.
It ought to be remembered in this whole discussion that the
epithelium of ordinary glands derives its supplies of material from
the tissue lymph. The vicissitudes of blood-pressure affect it only
in a secondary and indirect manner. On the other hand, the endo-
thelial cells of the capillaries are in direct contact with the blood.
And it is interesting to observe that in this respect the glomeruli
of the kidney and the alveoli of the lungs (if the endothelial lining
of Bowman's capsule and the alveolar membrane are assumed to
be complete) take a middle place between the glands proper and
the quasi-glandular capillaries.
CHAPTER IX
EXCRETION
WE have now followed the ingoing tide of gaseous, liquid, and solid
substances within the physiological surface of the body. There we
leave them for the present, and turn to the consideration of the
channels of outflow, and the waste products which pass along them.
In a body which is neither increasing nor diminishing in mass the
outflow must exactly balance the inflow; all that enters the body
must sooner or later, in however changed a form, escape from it
again. In the expired air, the urine, the secretions of the skin, and
the faeces, by far the greater part of the waste products is elimin-
ated. Thus the carbon of the absorbed solids of the food is chiefly
given off as carbon dioxide by the lungs; the hydrogen, as water
by the kidneys, lungs and skin, along with the unchanged water
of the food ; the nitrogen, as urea by the kidneys. The f seces in
part represent unabsorbed portions of the food. A small and
variable contribution to the total excretion is the expectorated
matter, and the secretions of the nasal mucous membrane and
lachrymal glands. Still smaller and still more variable is the loss
in the form of dead epidermic scales, hairs, and nails. The dis-
charges from the generative organs are to be considered as excre-
tions with reference to the parent organism, and so is the milk, and
even the foetus itself, with respect to the mother.
Excretion by the lungs and in the faeces has been already dealt
with. All that is necessary to be said of the expectoration and
the nasal and lachrymal discharges is that the first two generally
contain a good deal of mucin, and are produced in small mucous
and serous glands, the cells of which are of the same general type
as those of the mucous and serous salivary glands. The lachrymal
glands are serous like the parotid ; and the tears secreted by them
contain some albumin and salts, but little or no mucin. The sexual
secretions and milk will be best considered under reproduction
(Chap. XIX.), so that there remain only the urine and the secre-
tions of the skin to be treated here.
475
EXCRETION
SECTION I. — EXCRETION BY THE KIDNEYS — THE CHEMISTRY OF
THE URINE.
Normal urine is a clear yellow liquid acid to litmus and similar
indicators, but nearly neutral or very weakly acid in the physico-
chemical sense (p. 24). The average specific gravity is about 1020,
the usual limits being 1015 and 1025, although when water is taken
in large quantities, or long withheld, the specific gravity may fall
to 1005, or even less, or rise to 1035, or even more. The quantity
passed in twenty-four hours is very variable, and is especially
dependent on the activity of the sweat-glands, being, as a rule,
smaller in summer when the skin sweats much, than in winter when
it sweats little. The average quantity for an adult male is 1,200 to
1,600 c.c. (say, 40 to 50 oz.).*
Composition of Urine. — This is very closely related to the quantity
and quality of the food. Hence it is impossible to speak of a
definite normal composition of the urine. It is essentially a solu-
tion of urea and inorganic salts, the proportion of the latter being
generally about 1-5 per cent., or double the usual amount of physio-
logical liquids. Besides urea, there are other nitrogenous bodies
in much smaller quantity, such as ammonia, uric acid, and the
allied purin bases, hippuric acid, and kreatinin. Some of these at
least are products of the metabolism of proteins within the tissues.
And besides the inorganic salts there are certain organic bodies —
indoxyl, phenyl, pyrokatechin", skatoxyl — united with sulphuric
acid, which are primarily derived from the products of the putre-
faction of proteins within the digestive tube.
Folin has published analyses of ' normal ' urines from six persons,
weighing from 56-6 to 70-9 kilos (average 63-4 kilos), who were kept
for seven days on one standard uniform diet. The diet consisted of
500 c.c. of milk, 300 c.c. of cream (containing 18 to 22 per cent, of fat),
450 grammes of ^ggs, 200 grammes of Horlick's malted milk, 20 grammes
of sugar, 6 grammes of sodium chloride, water enough to make the
whole up to two litres, and 900 c.c. of additional water. The ingredients
contained 119 grammes of protein, about 148 grammes of fat, and
225 grammes of carbo-hydrates. The average results of all the deter-
minations are given in the following table :
* The average quantity of urine varies not only with the season, but also
with the habits of the person, especially as regards the amount of liquid
taken. The average for seventeen healthy (American) students, whose urine
was collected for six to eight successive days in winter, was 1,166 c.c. The
highest average in any one individual for the observation period was 1,487 c.c.
(for seven days), and the lowest 743 c.c. (for eight days). The greatest quan-
tity passed in any one period of twenty-four hours was 2,286 c.c. (by the in-
dividual whose average was the highest). The smallest quantity passed in
twenty-four hours was 650 c.c. (by the individual whose average was the
lowest.
47
Grammes.
Containing
Nitrogen
(Grammes).
Percentage
of Total
Nitrogen.
Urea -
Ammonia
Kreatinin -
Uric acid -
Nitrogen in other compounds
29-8
*'55
o-37
I3'9
0-70
0-58
O'I2
0-60
87-5
4'3
3.6
0-8
3'75
Total nitrogen
—
16-00
—
Inorganic SO3 ...
Ethereal SO3 - - - -
' Neutral ' SO3
2-92
0-22
O'I7
Percentage of Total
Sulphur.
87-8
6-8
5'i
Total sulphur as SO3
3'3I
Total phosphates as P2O5 -
Chlorine
3-87
6'i
Titratable acidity in c.c. of decinormal acid - 617
Indican (Fehling's solution =100*) - "77
Volume of urine ...
organic,
- 1430 c.c.
The great influence of diet on the composition of the urine is illus-
trated in the following table. Urine I. was obtained from a man weigh-
ing 87 kilos on the standard protein-rich diet described above. Urine II.
was obtained from the same person on a diet very poor in protein
(400 grammes of starch and 300 c.c. of cream), containing only about
i gramme of nitrogen, as against 19 grammes in the first diet.
I.
II.
Volume of urine
1170
c.c.
3850
.c.
Grammes.
Per Cent.
Grammes.
Per Cent.
Total nitrogen -
16-8
3-60
Urea-nitrogen -
14-70 =
87-5
2-2O =
61*7
Ammonia-nitrogen
0-49 =
3-o
0-42 =
n-3
Uric acid-nitrogen
O'i8 =
i-i
O'O9 =
2'5
Kreatinin-nitro ge n
0-58 =
3-6
0-60 =
17-2
Nitrogen in other compounds -
0-85 =
4'9
0'27 =
7'3
Total SO3
3-64
Inorganic SO3 •
3'27 =
90-0
0-46 =
60-5
Ethereal SO3
0-19 =
5'2
O-IO =
13-2 .
Neutral SO3'
0-18 =
4-8
0-20 =
26-3
Total phosphates as P2O5
4'i
I'O
Chlorine - 6-1
1-6
mineral, 398 /mineral, 123.
organic, 407 ^ ^(organic, 201
120 - o
* The indican is given in arbitrary units, the indigo blue being obtained
from the urine and then estimated colorimetrically, using Fehling's solu-
N (
Titratable acidity in c.c. -- acid - 805-^
Indican (Fehling's solution = 100)
EXCRETION
The titrable acidity of urine (see p. 25) is chiefly due to the acid (mono-
basic) phosphates, such as acid sodium phosphate (NaH2PO4), but in
an important degree also to organic acids. According to Folin, indeed,
the organic acidity may be more than half the total acidity. Normally
the acidity diminishes distinctly, or even gives place to alkalinity,
during digestion, when the acid of the gastric juice is being secreted.
This is sometimes fancifully denominated the alkaline tide. After a
fast, as before breakfast, the opposite condition, the acid tide, occurs.
The acidity varies with the quantity of vegetable food in the diet.
The urine of herbivora and vegetarians is alkaline, and is either turbid
when passed, or on standing soon becomes turbid from precipitated
carbonates and phosphates of earthy bases, while that of carnivora
and of fasting herbivora, which are living on their own tissues, is
strongly acid and clear. Normal human urine may deposit urates soon
after discharge, as they are more soluble in warm than in cold water.
They carry down some of the pigment, and therefore usually appear as
a pink or brick-red sediment. When urine is allowed to stand after
being voided, what is generally described as ' acid fermentation ' occurs.
The acidity gradually increases; acid sodium urate is produced from
the neutral urate, and comes down in the form of amorphous granules,
while the liberated uric acid is deposited often in ' whetstone ' crystals,
coloured yellow by the pigment (Fig. 177). Calcium oxalate may also
Fig. 177. — Uric Acid
Fig. 178.— Calcium Oxalate
be thrown down as ' envelope/ a, b, or less frequently, ' sand-glass '
crystals, c (Fig. 178). If the urine is allowed to stand for a few days,
especially in a warm place, or in a place where urine is decomposing,
the reaction becomes ultimately strongly alkaline, owing to the forma-
tion of ammonium carbonate from urea by the action of micro-organ-
isms (Micrococcus urece, Bacterium urees, and others) which reach it
from the air, and produce a soluble ferment urease, in whose presence
the urea is split up with assumption of water. Thus :
/NH2 /O.NH,
C=0 +2H20 - C=0
\NH2 \O.NH4,
Urea.
Ammonium carbonate.
This is a reaction of considerable interest, for the reverse reaction
occurs when blood containing ammonium carbonate is circulated
through the liver, the ammonium carbonate being converted into urea
with loss of water. The enzyme urease is present in higher plants than
bacteria and fungi. A solution containing it, conveniently prepared
from the soy bean, can be used for the quantitative estimation of urea,
and this is probably the easiest and most accurate method.
tion as a standard. Fehling's solution is employed because it is a blue liquid
of a definite depth of tint already prepared in every physiological laboratory.
479
The substances insoluble in alkaline urine are thrown down, the
deposit containing ammonio-magnesic or triple phosphate, formed by
the union of ammonia with the magnesium phosphate present in fresh
urine, and precipitated as clear crystals of ' knife-rest ' or ' coffin-lid '
shape (Fig. 179), along with amorphous earthy phosphates, and often
acid ammonium urate in the form of dark balls occasionally covered
with spines (Fig. 182). Calcium phosphate (CaHPO4) is another phos-
phate found in sediments deposited from alkaline or faintly acid urine.
It is usually amorphous, but sometimes in the form of long prismatic
crystals arranged in star fashion, and hence spoken of as stellar phos-
phate (Fig. 181). It is not pigmented.
It is only in pathological conditions that the alkaline fermentation
takes place within the bladder. The reaction of the urine can readily
o
Fig. 179. — Triple Phosphate. Fig. 180. — Cystin.
Fig. 181.— Stellar Phos-
phate Crystals.
be made alkaline by the administration of alkalies, alkaline carbonates,
or the salts of vegetable acids like malic, citric, and.tartaric acid, which
are broken up in the body and form alkaline carbonates with the alkalies
of the blood and lymph. It is not so easy to increase the acidity of the
urine, although mineral acids do so up to a certain limit. If the admin-
istration of acid be pushed farther, ammonia is split off from the pro-
teins, and is excreted in the urine as the ammonium salt of the acid.
Determination of the Acidity. — A titration method is described in
the Practical Exercises (p. 515). In speaking of the reaction of blood,
it has already been mentioned (p. 25) that we can-
not determine by titration the true acidity or alka-
linity of a liquid in the physico-chemical sense — i.e.,
the concentration of the dissociated hydrogen and
hydroxyl ions respectively. E.g., when we titrate
equal quantities of decinormal* acetic acid and deci-
normal hydrochloric acid with decinormal potassium
hydroxide, using, say, phenolphthalein as the indi-
cator, nearly the same volume of the potassium
hydroxide solution will be needed to neutralize each
acid. Yet it can be shown by physico-chemical
methods that the acetic acid in the strength used is
only dissociated to the extent of a little more than i per cent., while
about 80 per cent, of the hydrochloric acid is dissociated. The concen-
tration of the hydrogen ions is therefore eighty times as great in the
hydrochloric as in the acetic acid solution. What we determine by the
titration is not the true acidity , but the total amount of hydrogen which
can be replaced by metal. The concentration of the hydrogen ions in
normal urine is very small, on the average only about 0-003 milli-
* A normal solution of a substance contains in a litre a number of grammes
of the substance equal to the number which expresses its equivalent weight
— a decinormal (usually written ^) solution one-tenth of this amount, a
centinormal one-hundredth, etc. Thus, a normal solution of potassium
hydroxide contains 56 grammes of KOFI, and a decinormal solution 5*6
grammes in 1,000 c.c.
Fig. 182. — Ammo-
nium Urate (after
Milroy).
48« EXCRETION
gramme in the litre, or about thirty times as much as is present in the
purest distilled water. Urine departs about as much from neutrality in
the one direction as blood does in the other.
Urea, CO(NH2)2, is the form in which by far the greater part of the
nitrogen is under ordinary conditions discharged from the body. Its
amount is as important a measure of protein metabolism as the quantity
of carbon dioxide given out by the lungs is of the oxidation of carbon-
aceous material. Yet a glance at the table on p. 477 shows that, when
the total protein metabolism is greatly reduced by diminishing the
protein in the food, the relative as well as the absolute amount of
nitrogen eliminated as urea suffers a great diminution. The relative
amount of the other nitrogenous urinary constituents, especially of
the kreatinin, is markedly increased. The significance of this difference
is alluded to in speaking of the kreatinin content of urine, and will have
to be again considered under Protein Metabolism. Urea is soluble in
water and in alcohol, and crystallizes from its solutions in the form of
long colourless needles, or four-sided prisms with pyramidal ends. It
can be easily prepared from urine. Urea can also be obtained artificially
by heating its isomer, ammonium cyanate (NH4 — O— CN), to 100° C.
This reaction is of great historical interest, as it forms the final step
in Wohler's famous synthesis of urea, the first example of a complex
product of the activity of living matter being formed from the ordinary
materials of the laboratory. Heated in watery solution in a sealed
tube to 1 80° Ci, urea is entirely split up into carbon dioxide and am-
monia, a change which can also be brought about, as already mentioned,
by the action of micro-organisms. Nitrous acid, hypochlorous acid, and
salts of hypobromous acid carry the decomposition still farther, carbon
dioxide, nitrogen, and water being the products of their oxidizing action
on urea. Thus: CO.2(NH2) +3NaBrO=3NaBr + 2H2q+CO2+ N2.
This reaction is the basis of the hypobromite method of estimating the
quantity of urea in urine (Practical Exercises, p. 319).
Ammonia. — The ammonia in urine is united with acids in the form
of salts. Its formation from proteins is determined, as we shall see
later on, by the necessity of neutralizing certain acids produced in
metabolism — e.g., those derived from the sulphur and phosphorus of the
proteins, or acids administered experimentally. According to some
observers, the percentage amount of the total nitrogen in the urine
in the form of ammonia remains the same whether the food be rich or
poor in protein (Schittenhelm, etc.), but others state that when the
protein is reduced there is a relative increase in the ammonia-nitrogen
(see table on p. 477) (Folin).
Uric acid (QH^l^Cy exists in large amount in the urine of birds.
The excrement of serpents consists almost entirely of uric acid. In
both cases it is mainly in the form of acid ammonium urate. In con-
trast to urea, uric acid is very insoluble, requiring 1,900 parts of hot
and 15,000 parts of cold water to dissolve it. In man and mammals
the quantity is comparatively small in health, but is increased after
a meal containing material (e.g., thymus gland) rich in nucleins,
from the nucleic acid of which purin bodies are derived, or sub-
stances containing purin bases in the free state — e.g., hypoxanthin
in meat. In mammals the amount of uric acid excreted depends
little, if at all, upon the quantity of protein in the food, but a great deal
upon the quantity of purin bodies, whether free or combined. When
nitrogenous food is omitted altogether, the absolute quantity of uric
acid is diminished, but the proportion of the total nitrogen of the urine
eliminated rs uric acid is increased, since the ' endogenous ' uric acid
(p. 596) still continues to be formed and excreted.
CHEMISTRY OF URINE
481
The purin bases (sometimes called the nuclein bases, the alloxuric
bases, or the xanthin bases) are a group of substances allied to uric
acid, and including, besides xanthin itself, hypoxanthin, guanin, adenin,
and other bodies. They exist in very small amount in urine, but, like
uric acid, are increased in amount by the ingestion of nuclein-contain-
ing substances. The greater part of the purin bases produced in the
body is transformed into uric acid ; it is only the untransformed residue
which appears in the urine. An interesting fraction of the purin bases
in the urine which is not related to the nuclein metabolism is composed
of the so-called heteroxanthin, derived from caffeine in the coffee and
tea, /-methylxanthin, derived from theobromine in the cocoa, and para-
xanthin, derived from theophyllin in the tea, consumed as beverages.
Hippuric acid (C9H9NO3) occurs in considerable quantity in the urine
of herbivora (Practical Exercises, p. 524); in the urine of carnivora and
of man only in traces; in that of birds not at all. Its amount is much
more dependent on the presence of particular substances in the food
than that of the other organic constituents of urine. Anything which
contains benzoic acid, or substances which can be readily changed into
it (such as cinnamic and quinic
acids), causes an increase of the
hippuric acid in urine. In fact,
one of the best ways of obtaining
the latter is from the urine of a
person to whom benzoic acid is
given by the mouth; the sweat
Fig. 183.— Creatin.
Fig. 184. — Creatinin-Zinc-Chloride.
may also in this case contain a trace of hippuric acid. Chemically it
is a conjugated acid formed by the union of benzoic acid and glycin.
Amino-Acids. — The only amino-acid hitherto detected with certainty
in normal urine is glycin.
Oxalic acid is always present, although in very small amount. Some
of it comes from the oxalates of the food, but a portion of it arises in
the metabolism of the tissues, probably from the decomposition of uric
acid. It is known that outside of the body uric acid may be made to yield
oxalic acid. Calcium oxalate crystals are -often seen in urinary sediments.
Creatinin (C4H7N3O). — Creatinin is the anhydride of creatin
(Fig. 183). Its formula differs from that of creatin only in possessing
the elements of one molecule of water less; and creatinin can be
obtained by boiling creatin with dilute sulphuric acid. From its
alcoholic solution it crystallizes in colourless prisms. Creatinin forms
crystalline compounds with various acids and salts. One of the best
known of these is creatinin-zinc-chloride, formed on the addition of
zinc chloride to an alcoholic or waterv solution of creatinin, often in
the shape of beautiful thick-set rosettes of needles (Fig. 184). A por-
482 EXCRETION
tion of the urinary creatinin is derived from the creatin of the meat
taken as food. But this is not its only source, for on a meat-free diet
and in starvation creatinin is still excreted. The absolute quantity in
the urine on a meat-free diet is constant for one and the same individual,
although different in different persons, and independent of the total
amount of nitrogen eliminated. Hence on a diet poor in protein the
percentage of the total nitrogen excreted as creatinin is much greater
than on a protein-rich diet, as shown in the table on p. 477. So constant
is the quantity that a determination of the creatinin may be used as a
check upon the complete collection of the urine.
Carbo-hydrates are normally present in human urine, but only in
very small amounts. Three are known with certainty — dextrose,
isomaltose, and the so-called animal gum or urine dextrin. Glycuronic
acid (C6H10O7), a body which can be derived from dextrose, is con-
stantly present in small amount as a conjugated acid, paired with
phenol or indoxyl. It gives Fehling's test, and thus may easily be
mistaken for sugar. Glycuronic acid becomes coupled very easily with
a large variety of substances, including many drugs, and care must be
taken after the administration of camphor, chloral hydrate, chloro-
form, nitrobenzol, etc., not to confound the largely increased excretion
of conjugate glycuronates in the urine with glycosuria. The yeast test
will turn out negative if the reduction is due to glycuronic acid, and
the polarimeter will show rotation to the right if it is due to dextrose.
The total quantity of carbo-hydrates, including glycuronic acid,
excreted in the urine of the twenty-four hours has been estimated at
2 to 3 grammes. The quantity of dextrose in normal human urine is
about 0-02 per cent., or about one-fifth of the proportion in blood.
Proteins, mainly serum-albumin, are also found in normal urine in
minute quantities, on the average about 0-0036 per cent. (Morner).
Pigments of Urine. — The pigments of urine have not hitherto been
exhaustively studied ; but we already know that normal urine contains
several, and pathological urines probably additional, pigmentary sub-
stances. The best-known pigments in normal urine are urochrome,
the yellow substance which gives the liquid its ordinary colour;
uroerythrin, the pink pigment which often colours the deposits of urates
that separate even from healthy urine ; and urobilin, which, as has been
already stated, is identical with the faecal pigment stercobilin, and occurs
not only in many febrile conditions, but also in cases with no fever, such
as functional derangements of the liver, dyspepsia, chronic bronchitis,
and valvular diseases of the heart. The urobilin of urine represents,
mainly at least, the portion of the stercobilin which is not excreted with
the faeces, but absorbed from the intestine into the blood. The urobilin
in normal urine only exists in small amount in the fully-formed con-
dition, most of it being present as a chromogen or mother-substance
(urobi Imogen), which by oxidation, as on standing exposed to the air,
is converted into urobilin. On the addition of ammonia and zinc
chloride to a solution of urobilin a beautiful green fluorescence is
obtained, and the solution now shows an absorption band between
b and F. Urobilin and urochrome are related substances, bat the exact
nature of the relation has not been settled. There is some evidence
that a portion of the urobilin of urine is not derived from the intestine,
but manufactured probably in the liver. In hunger urobilin is still
excreted in the urine, although in greatly reduced amount. During
menstruation it is markedly increased, both in fasting and in normally
fed individuals. Urorosein is a red pigment which is produced from
its chromogen by the action of mineral acids — e.g., strong hydrochloric
acid — in the presence of an oxidizing agent, especially nitrites.
CHEMISTRY OF URINE
483
The pigments of the blood and bile and some of their derivatives are
of common occurrence in the urine in disease. Hcematoporphyrin has
not only been found in some pathological conditions, but is constantly
present in minute traces in normal urine. Certain drugs — e.g., sulphonal
— cause an increase in its amount. In paroxysmal hsemoglobinuria,
methcsmoglobin, mixed with some oxyhaemoglobin, is found in the urine in
large amount ; and it is worthy of note that it is not formed in the urine
after secretion, but is already present as such when it reaches the bladder.
In the rare condition termed alkaptonuria, a body, alkapton, now
known to be identical with homogentisinic acid, C6H3.(OH)2CH2.COOH,
a dioxyphenylacetic acid, is present. The urine becomes dark brown
on the addition of an alkali, or simply on exposure to air. It gives
Fehling's test for sugar. The substance has relations to the aromatic
amino-acids tyrosin and phenyl-alanin, and when either of these is
given to a person suffering from alkaptonuria, the amount of alkapton
excreted is increased. We may suppose, therefore, that in this con-
dition the normal decomposition of these products of proteolysis is
interfered with.
Ferments. — The urine contains traces of proteolytic and amylolytic
ferments (Fig. 185). These may be easily separated from it by putting
a little fibrin, which has the power of fixing (adsorbing) enzymes, into
the urine.
Of the inorganic constituents of urine the most important and
most easily estimated are the chlorine, phosphoric acid, and sul-
phuric acid.
Fig. 185. — Pepsin in Urine. Diastatic Ferment in Urine.
At Different Times of the Day (Hoffmann).
Chlorine. — Much the greater part of the chlorine is united with
sodium, a smaller amount with potassium. The chlorides of the urine
are undoubtedly to a great extent derived directly from the chlorides
of the food, and have not the same metabolic significance as the organic,
and even as some of the other inorganic constituents. But it is note-
worthy that in certain diseased conditions the chlorine may disappear
entirely from the urine, or be greatly diminished — e.g., in pneumonia,
and in general in cases in which much material tends to pass out ffom
the blood in the form of effusions (p. 515).
Phosphoric Acid. — The phosphoric acid of the urine is chiefly derived
from the phosphates of the food, but must partly come from the waste
products of tissues rich in phosphorus-containing substances, such as
lecithin and nuclein. The phosphoric acid is united partly with alkalies,
especially as acid sodium phosphate, and partly with earthy bases, as
phosphates of calcium and magnesium. The earthy phosphates are
precipitated by the addition of an alkali to urine, or in the alkaline
484
EXCRETION
'lermentation. In some pathological urines they come down when the
carbon dioxide is driven off by heating; a precipitate of this sort differs
from heat-coagulated albumin in being readily soluble in acids (Practical
Exercises, p. 524). A small amount of phosphorus may appear in the
urine in a less oxidized form than phosphoric acid.
Sulphuric Acid. — This is only to a slight extent derived from ready-
formed sulphates in the food. The greater part of it is formed by
oxidation of the sulphur of proteins. About nine-tenths of the sulphur
in normal urine is present as inorganic sulphates, mainly those of
potassium and sodium. Of the other tenth, a portion is represented
by ethereal sulphates, and the remainder by the so-called ' neutral '
sulphur, including the sulphur associated with the pigment urochrome.
A small amount of sulphur occurs in less oxidized forms than sul-
phates in such compounds as the sulphocyanide, which is probably,
in part but not entirely, derived from that of the saliva, and ethyl
sulphide, a substance with a penetrating odour, which appears to be a
constant constituent of dog's urine (Abel).
Thiosulphuric acid (H2S2O3) occurs almost constantly in cat's urine,
often in dog's. It is not free, but combined with bases.
The ethereal sulphates are compounds in which the sulphuric acid is
united with aromatic, bodies (indol, phenol, etc.). Such are potassium-
phenyl-sulphate (C6H5KSO4), potassium-kresyl-sulphate (C7H7KSO4),
potassium-indoxyl-sulphate (C8H6NKSO4) , potassium-skatoxyl-sulphate
(CjHgNKS^), and two double sulphates of potassium and pyrocatechin.
The formation of potassium indoyxl sulphate may be thus represented :
Indol, CftH4v I^TT' " on absorption from the intestine is changed into
v /C OH CH /OH
indoxyl, CeH4\NH ' which + SO2<^OK (potassium hydrogen
sulphate) yields SO2\Qj/ e (potassium indoxyl sulphate) + H8O.
The ' pairing ' of these aromatic bodies with sulphuric acid renders
them innocuous to the organism. Most of the compounds are present
in greater amount in the urine of the horse than in the normal urine of
man. But in disease the quantity of indican in the latter may be much
increased ; and to a certain extent it must be looked upon as an index
of the intensity of putrefactive processes in the intestine and of absorp-
tion from it. Munk made the observation that in the urine of a starving
dog the phenol-forming substances are absent, while in the urine of a
starving man they are present in abnormally large amount. The
indigo-forming substances (indican), on the other hand, are in hunger
excreted in considerable quantity by the dog, and not at all by man
(Practical Exercises, p. 518). According to Folin, the indoxyl potassium
sulphate or indican of the urine is not to any appreciable extent related
to protein metabolism, but for the most part to the putrefaction of
protein in the intestine. The indoxyl-potassium sulphate taken by itself
may therefore afford a rough index of the intensity of the intestinal
putrefactive processes. On the other hand, the total ethereal sulphuric
acid cannot be taken as an index of the extent of the putrefaction, for,
although absolutely diminished, it is increased relatively to the total
excretion of sulphur on a diet poor in protein, or even protein-free
(see tables on p. 477).
Phenol and kresol can easily be obtained from horse's urine by
mixing it with strong hydrochloric acid and distilling. These aromatic
bodies pass over in the distillate. Pyrocatechin remains behind, and
can be extracted by ether. It gives a green colour with ferric chloride,
which becomes violet on the addition of sodium carbonate.
CHEMISTRY OF URINE
485
The sulphur of the inorganic sulphates is the fraction of the total
sulphur which fluctuates in proportion to the total protein metabolism.
In this regard it follows the variations in the urea. It represents
' exogenous ' metabolism. The neutral sulphur occupies a position
analogous to that of the creatinin : the smaller the amount of protein
in the food, and the smaller therefore the total protein decomposed, the
larger is the fraction which the neutral sulphur forms of the total
sulphur. The neutral sulphur accordingly represents endogenous
metabolism. The ethereal sulphur takes an intermediate position in
this regard, but upon the whole it also becomes a more prominent
fraction of the total sulphur when the food contains little or no protein.
The ethereal sulphates are therefore not entirely derived from the
putrefaction of protein.
Carbonates of sodium, ammonium, calcium, and magnesium occur
in alkaline urine. Their source is the carbonates and the vegetable
organic acids of the food. In acid urine a certain amount of carbon
dioxide is present, although not firmly united with bases, so that most
of it can be pumped out.
So-called Physico-Chemical Analysis of Urine.— The freezing-point
of urine has often been determined to obtain a measure of the mole-
cular concentration, which with the total quantity of urine secreted
in a given time was erroneously assumed to afford an index of the
work done by the kidney. Clinically the method is of little use, but
for certain physiological questions freezing-point determinations are
of value and are sometimes combined with determinations of the
electrical conductivity, by which we obtain an approximate measure
of the number of dissociated ions in unit volume, mainly the inorganic
salts. Normally, A has a higher value for urine than for blood — i.e.,
the molecular concentration of the urine is higher than that of the
serum. But when large draughts of water are taken A may be lower
for urine than for blood, and in general it varies within far wider
limits (from 0-115° to 2-546° C., according to Koppe). The following
table from Kovesi and Roth-Sch,ulz shows the changes in A under the
influence of water :
Time.
Urine in C.C.
A
10 to 2
240
I -80
2 to 6
255
I'72
6 to 10
161
i-93
IO to 2
131
2-18
2 to 6
1 60
2-23
6 to i»
I2O
1-91
II to 12
1-8 litres ' Salvator ' water taken
—
12 tO 12.30
500
0-12
12.30 to i
444
O'll .
i to 1.30
442
O'lO
1.30 to 2
46
0-78
2 to 2.30
45
1-30
The Urine in Disease. — Although, strictly speaking, a truly patho-
logical urine has no place in physiology, the line which separates the
urine of health from that of disease is often narrow, sometimes invisible ;
while the study of abnormal constituents is not only of great importance
in practical medicine, but throws light upon the physiological processes
486 EXCRETION
taking place in the kidney, and upon the general problems of metabolism.
Even in health the quantity of the urine, its specific gravity, its acidity,
may vary within wide limits. A hot day may increase the secretion
of sweat, and correspondingly diminish the secretion of urine, and the
deficiency of water may lead to a deposit of brick-red urates. A meal
rich in fruit or vegetables may render the urine alkaline, and its alkalinity
may determine a precipitate of earthy phosphates. But neither the
scanty acid urine with its sediment of urates, nor the alkaline urine
with its sediment of phosphates, somes into the category of pathological
urines; the deviation from the normal does not amount to disease.
The maximum deviation from the line of health is the total suppression
of the urine. If this lasts long, a train of symptoms, oi which con-
vulsions may be one of the most prominent, and which are grouped
under the name of uraemia, appears. At length the patient becomes
comatose, and death closes the scene. Suppression of urine may be
the consequence of many pathological conditions, but there is one case
on record in the human subject which, in effect, though not in intention,
belongs to experimental physiology. A surgeon diagnosed a floating
kidney in a woman. With a natural impatience of loose odds and
ends of this sort, he offered to remove it, and in an evil hour the patient
consented. The surgeon, a perfectly skilful man, who acted for the
best, and to whom no blame whatever attached, carried the kidney to
a well-known pathologist for examination. The latter, to the horror
of the operator, suggested, from the appearance of the organ, that it
was the only kidney the woman possessed. This turned out to be the
fact. Not a drop of urine was passed. Apart from this ominous
symptom, all went well for seven or eight days; but then uraemic
troubles came on, and the patient died on the eleventh or thirteenth
day after the operation. The necropsy showed that her only kidney
had been taken away.
In disease the urine may contain abnormal constituents, or ordinary
constituents in abnormal amounts. Of the normal constituents which
may be altered in quantity, the most important are the water, the inor-
ganic salts, the urea, the uric acid, and the aromatic substances.
Water. — A marked and persistent diminution in the quantity of
urine — that is to say, practically in the water, with or without an
increase in the specific gravity — is suggestive of disorganization of the
renal epithelium. In some infective diseases the kidney is liable to
be secondarily involved, its secreting cells being perhaps crippled in the
attempt to eliminate the bacterial poisons. In the form of paren-
chymatous or tubal nephritis which so frequently complicates scarlet
fever, the quantity of urine has in some cases fallen to 50 or 60 c.c. in
the twenty-four hours.
In chronic interstitial nephritis (' granular kidney '), on the other
hand, where the structural changes in the tubules are, for a long time
at least, comparatively circumscribed, the quantity of urine is often
increased and of low specific gravity. In these cases the increase in
the blood-pressure, associated with hypertrophy of the heart, may be
a factor in the exaggerated renal secretion. In diabetes mellitus the
quantity of urine is greatly increased, perhaps in some cases because
more urea is excreted than normal, and urea acts as a diuretic, perhaps
also because the elimination of sugar draws with it an increased excretion
of water to hold it in solution. Although a specific gravity as low as
1002 has been seen in healthy persons (after copious potations), the
persistence of a density below 1010 should suggest hydruria. Watson
mentions the case of a boy with diabetes insipid us, who voided in
twenty-four hours 9 or 10 pints (5 to 6 litres) of urine with a specific
gravity of 1002. On the other hand, while the specific gravity has been
CHEMISTRY OF URINE 487
occasionally observed to mount in health to at least 1036, its persistence
at 1025 or 1030 CT anything above this, especially if the urine is pale
and apparently dilute, should suggest diabetes mellitus.
Inorganic Salts. — The changes in the quantity of the inorganic con-
stituents of the urine in disease are not, in the present state of our
knowledge, of as much importance as the changes in the organic con-
stituents. The chlorides are diminished in most acute febrile diseases
and may even totally disappear from the urine, and their reappearance
after the crisis is, so far as it goes, a favourable symptom. In most
cases in which the quantity of the urine is markedly lessened, all the
inorganic substances are diminished in amount.
Urea. — The quantity of urea is, as a rule, increased in fever, either
absolutely or in proportion to the amount of nitrogen in the food. In
the interstitial varieties of kidney disease the urea is usually not
diminished, but when the stress of the change falls on the tubules
(parenchymatous nephritis), it is distinctly decreased — it may be even
to one-twentieth of the normal.
Uric acid is diminished in the urine in gout (perhaps to one-ninth of
the normal), not only during the paroxysms, but in the intervals. It
accumulates in the blood and tissues, and, as sodium urare, may form
concretions in the joints, the cartilage of the ear, and other situations.
Watson relates the case of a gentleman who used to avail himself of his
resources in this respect by scoring the points at cards on the table with
his chalky knuckles. In leukaemia the quantity of uric acid and purin
bases in the urine is greatly increased, not only absolutely, but also in
proportion to the urea. As much as 4^ grammes of free uric acid, in
addition to about ij grammes of ammonium urate, has been found in a
urinary sediment in a case of leukaemia.
The aromatic bodies, of which indoxyl may be taken as the type,
are increased when the conditions of disease favour the growth of
bacteria in the intestine — e.g., in cholera, acute peritonitis, and carci-
noma of the stomach. A marked increase in the amount of the indican
in the urine may, as far as it goes, be taken as an indication that the
bacteria are gaining the upper hand in the intestinal tract; a marked
diminution is usually a sign that the battle has begun to turn in favour
of the organism (Practical Exercises, p. 517). Tryptophane, a sub-
stance which we have already recognized among the products of the
tryptic digestion of proteins, has been shown to be a precursor of indol,
which is formed from it under the influence of bacteria. When trypto-
phane is injected into the caecum of rabbits, the indican in the urine
is markedly increased. Putrefactive processes in other parts of the
body than the intestine may also increase the indican in the urine —
e.g., a collection of putrid pus in the pleural cavity.
Abnormal Substances in Urine. — Sugar, proteins, the pigments of bile
and blood, or their derivatives, are the most important abnormal sub-
stances found in solution in the urine. Normal urine, as has been
stated, contains a trace of dextrose, but so little that it cannot be
detected by ordinary tests, and for practical purposes it may be .con-
sidered absent. Dextrose is the sugar found in the urine in diabetes.
In the urine of nursing mothers lactose may be present. Pentoses,
sugars with five carbon atoms in the molecule (instead of six, as in the
hexoses, of which group dextrose is a member), may also occasionally
occur in urine. Pentoses give the ordinary reduction tests for sugar,
and yield osazones, but do not ferment with yeast. Various plants
contain pentoses, and when these are eaten the pentoses are excreted
in the urine, but in cases of true pentosuria they originate in the body,
possibly from nucleo-proteins. The condition has not the same sinister
significance as diabetes. Specific toxic substances produced by bac-
488 EXCRETION
terial action have been demonstrated in the urine in certain diseases.
Red blood-corpuscles and leucocytes (pus corpuscles, white blood-
corpuscles, mucous corpuscles) are the chief organized deposits; but
spermatozoa may occasionally be found, as well as pathogenic bacteria —
e.g., the typhoid bacillus; and in disease of the kidney casts of the renal
tubules are not uncommon. These tube-casts may be composed chiefly
of red blood -corpuscles, or of leucocytes, or of the epithelium of the
tubules, sometimes fattily degenerated, or of . structureless protein,
or of amyloid substance. Abnormal crystalline substances, stich as
the amino-acids, leucin (Fig. 186), tyrosin (Fig. 187), and cystin
(Fig. 1 80), may be on rare occasions found in urinary sediments; but
generally the unorganized deposits of pathological urine consist of
bodies actually contained in, or obtainable from, the normal secretion,
but present in excess, either absolutely, or relatively to the solvent
power of the urine. Cystin is of interest because of its relations to the
sulphur of the protein molecule (p. 360). It is not found in the normal
organism. It very occasionally forms calculi in the bladder. There
arc individuals who constantly pass as much as one-fourth of all the
sulphur in the form of cystin, without any other symptoms.
Various amino-acids are present in solution in the urine in many
pathological conditions. Of these the least soluble are leucin and
tyrosin, and this is the reason why they are most easily detected. A
general reaction for ammo-acids is their precipitation as sparingly
soluble compounds (|3-naphthalinsulphones) by /3-naphthalinsulpho-
cWpride in the presence of an alkali (sodium hydroxide). In acute
yellow atrophy of the liver leucin and tyrosin have been found in large
amounts in the liver itself, as well as in the urine. In phosphorus
poisoning these amino-acids, as well as glycocoll, have been detected in
the urine, and there is no doubt that other amino-acids, arising from
the decomposition of proteins, are also present in such conditions.
Sugar. — In diabetes mellitus, although the quantity of urine is usually
much increased, its specific gravity is above the normal; and this is due
chiefly to the presence of sugar (dextrose), which generally amounts
to i to 5 per cent., but may in extreme cases reach 10 or even 15 per •
cent., more than half a kilogramme being sometimes given off in twenty-
four hours.
The name of the tests for dextrose is legion. They are mostly
founded on its reducing action in alkaline solution. Hydrated oxide of
bismuth (Boettcher), salts of gold, platinum and silver, indigo (Mulder),
and a host of other substances, are reducsd by dextrose, and may
be used to show its presence. The reduction of cupric salts (Trommer),
Fig. 186. — Leucin Crystals. Fig. 187. — Tyrosin Crystals.
fermentation by yeast, and the formation of crystals of phenyl-gluco-
sazone are the best established tests. (See Practical Exercises, p. 517.)
Proteins. — Serum-albumin and serum-globulin are the proteins most
commonly found in pathological urine. Both are coagulated by heating
the urine, slightly acidulated if it is not already acid, or' by the addition
CHEMISTRY OF URINE 489
of strong nitric acid in the cold. Proteoses (albumoses) are also occa-
sionally present, e.g., in the disease called ' osteomalacia ' and in con-
ditions associated with the formation and especially with the decom-
position of pus. They may be recognized by the tests given in the
Practical Exercises (p. 525). It is doubtful whether the presence of
true peptone has as yet been satisfactorily made out.
The presence of bile-salts may be shown by Hay's test or Petten-
kofer's test (p. 46-2).
The pigments of blood and bile may be detected by the characters
described in treating of these substances; the spectrum of oxyhaemo-
globin, ormethaemoglobin, or any of the other derivatives of haemoglobin,
with the formation of haemin crystals, would afford proof of the presence
of the former, and Gmelin's test of the latter. The red blood-corpuscles,
seen with the microscope, are the most decisive evidence of the presence of
blood, as leucocytes in abundance are of the presence of pus. It should
be remembered that pus in the urine of women has sometimes no signifi-
cance except as showing that there has been an admixture of leucorrheal
discharge from the vagina. (See Practical Exercises, pp. 74, 531.)
SECTION II.— THE SECRETION OF THE URINE.
We have now to consider the mechanism by which the urine is
formed in the kidney from the materials brought to it by the blood.
And here the same questions arise as have already been discussed
in the case of the salivary and other digestive glands: (i) Are the
urinary constituents, or any of them, present as such in the blood ?
(2) If they do exist in the blood, can they be shown to be separated
from it by processes mainly physical or mainly ' vital ' — in other
words, by ordinary nitration, diffusion and osmosis, or by the selec-
tive action of living cells ? In the case of the digestive juices it
has been seen that some constituents are already present in the
blood, but that physical laws alone, so far as we at present under-
stand them, cannot explain the proportions in which they occur in
the secretions, or the conditions under which they are separated;
while other constituents — and these the more specific and important
— are manufactured in the gland-cells.
In the kidneys the conditions seem at first sight favourable to
physical separation, as opposed to physiological secretion. Urine
has been described as essentially a solution of urea and salts, and
both are ready formed in the blood. The arrangement of the blood-
vessels, too, suggests an apparatus for filtering under pressure.
Bloodvessels and Secreting Tubules of Kidney. — The renal artery splits
up at the hilus into several branches, which pass in between the Mal-
pighian pyramids, and form at the boundary of the cortex and medulla
vascular arches, from which spring, on the one side, interlobvlar arteries
running up into the cortex between the pyramids of Ferrein, and, on
the other, vasa recta running down into the boundary layer of the
medulla (Fig. 188). The interlobular arteries give off at intervals
afferent vessels. Each of these soon breaks up into a glomerulus or tuft
of vascular loops, which gather themselves up again into a single
efferent vessel of somewhat smaller calibre than the afferent. The
glomerulus is fitted into a cup or capsule (of Bowman), which is closely
490
EXCRETION
Pig. 1 88. — Diagram of Blood-
vessels of Kidney (Klein, after
Ludwig). ai, interlobular ar-
tery; vi, interlobular vein;
g, glomerulus, to which an
afferent artery is seen coming
from the interlobular artery,
and from which an efferent
artery proceeds to break up
into a capillary network sur-
rounding the renal tubules;
vs, vena stellata; ar, arteriae
rectae ; vb, leash of venae rectae ;
vp, vascular network round
ducts at apex of a papilla.
Fig. 189. — Diagram of Renal Tubule (Klein).
A, cortex ; a, layer of cortex immediately under
capsule containing no Malpighian corpuscles;
a', inner layer of cortex devoid of Malpighian cor-
puscles; B, boundary layer; C, papillary zone of
medulla; i, Bowman's capsule; 2, neck of cap-
sule; 3, proximal convoluted tubule; 4, spiral
tubule; 5, descending part of Henle's loop-
tubule; 6, the loop; 7, 8, and 9, ascending limb
of loop-tubule; 10, irregular tubule; n, distal
convoluted tubule; 12, junctional tubule; 13,
collecting tubule in a medullary ray or pyra-
mid of Ferrein; 14, collecting tubule in the
boundary layer; 15, large collecting tubule
ending in a duct of Bellini.
THE SECRETION OF THE URINE 491
reflected over it, except where the afferent and efferent vessels pass
through, and forms the beginning of a urinary tubule. If we suppose
the tuft plashed into the blind end of the tubule so as to indent it, it will
be easily understood that the single layer of flattened epithelium reflected
on the glomerulus is continuous with that lining the capsule, which in
its turn is continuous with the epithelial layer of the rest of the urinary
tubule. This has been divided by histologists into a number of parts
which it is unnecessary to enumerate here, further than to say that the
urinary tubule proper begins in the cortex in Bowman's capsule and
the proximal convoluted tubule (with its continuation, the spiral tubule),
and ends in the cortex with the distal convoluted tubule, the connection
between the two being made by a long loop (Henle's) with a descending
and an ascending limb (Fig. 189). Between the ascending limb and
the distal convoluted tube is interposed the zigzag tubule. The tubule
throughout its length is bounded by a basement membrane lined by a
single layer of epithelium, which differs in its character in different
parts of the tubule
The distal convoluted tubs joins by means of the short connecting
tubule one of the straight tubules which form the pyramids of Ferrein
or medullary rays in the cortex, and which run down into the medulla,
always uniting into larger and larger tubes as they go, until at length
they open as ducts of Bellini on the apex of a papilla. The two convo-
luted tubules (with the spiral and zigzag tubules) are lined by similar
epithelial cells with granular contents, and the tendency of the granules
to be arranged in rows perpendicular to the basement membrane gives
them a striated or ' rodded ' appearance (Fig. 190). The granules are
eosinophile (p. 17), which is also a character of the granules of other
secreting cells. Towards the lumen the cells may show a brush of pro-
cesses, looking like cilia, but in mammals these are not motile. The
ascending part of Henle's loop also has cells of the same general char-
acter, with numerous granules, although the ' rodding ' may not be so
distinct. We shall see directly that the morphological resemblance is
the index of a f unction »,1 likeness. The blood-supply of the tubules,
especially of the convoluted portions, is exceedingly rich, the efferent
vessels of the glomeruli breaking up around them into a close-meshed
network of capillaries, from which the blood is collected into inter-
lobular veins running parallel to the interlobular arteries between the
pyramids of Ferrein. The straight tubules of the medulla are also
surrounded by capillaries given off from straight arteries (arteriae
rectae) running down into it partly from the arterial arches and partly
from efferent vessels of the glomeruli nearest the boundary layer, the
blood passing away by straight veins (venae rectas) which join the larger
veins accompanying the arterial arches. The greater part of the
blood going through the kidney has to pass through two sets of capil-
laries, one in the glomeruli, the other around the tubules. Even the
portion of it which does not go through the glomeruli has for the most
part a long route to traverse in narrow arterioles and venules to and
from its capillary distribution. And the mean circulation-time through
the kidney has been found to be longer than that through most other,
organs (p. 137).
Theories of Renal Secretion. — To come back to our problem of
the nature of renal secretion, the anatomical structure of the kidney
might be expected to throw light upon the question. And, indeed,
it was on a purely histological foundation that Bowman established
his famous ' vital ' theory of renal secretion. Impressed with the
49« EXCRETION
resemblance between the renal epithelium and the epithelial cells
of other glands, and with the distribution of the bloodvessels in the
kidney, he came to the conclusion that the characteristic con-
stituents of urine, including urea, were secreted from the blood by
the tubules. To the Malpighian bodies he assigned what he doubt-
less considered the humbler office of separating water from the
blood for the solution of the all-important solids. To Ludwig, on
the other hand, with his whole attention fastened on the mechanical
factors by which the flow of urine could be influenced, the tubules
Fig. 190. — From a Vertical Section of Dog's Kidney to show the Structure of Different
Portions of the Renal Tubule (Klein), a, Bowman's capsule enclosing glomerulus,
the capillaries of which are arranged in lobules separated by a little connective
tissue. The capsule and glomerulus together constitute a Malpighian body or
corpuscle; n, neck of capsule; c, c, convoluted tubules, cut in various directions;
b, irregular or zigzag tubule; d, e, and/ are straight tubules, which take part in the
formation of a medullary ray or pyramid of Ferrein ; d, collecting tubule ; e, e, spiral
tubule; /, narrow part of ascending limb of Henle's loop-tubule; 6, c, and e are
lined with rodded epithelium.
seemed of secondary importance, while the glomeruli appeared a
complete apparatus for filtering urine from the blood into Bow-
man's capsule. He saw that the efferent vessel was smaller than
the afferent ; that it was therefore easier for blood to come to the
glomerulus than to get away from it, and that the pressure in the
capillaries of the tuft must be higher than in ordinary capillaries,
because the resistance beyond them in the comparatively narrow
efferent vessel, and especially in the second plexus, is greater than
the resistance beyond a single capillary network. And experi-
mental investigation soon showed him that the rate at which urine
THE SECRETION OF THE URTNE 493
was formed could be greatly influenced by changes in the blood-
pressure.
On such considerations, Ludwig founded the ' mechanical ' theory
of urinary secretion, which, although in a much' modified form, still
divides with the ' vital ' theory the allegiance of physiologists.
It is impossible here to enter in detail into a controversy that has
extended over more than half a century and produced an extensive
literature. The result of the discussion has been, in our opinion,
to establish in its essential principles the ' vital ' theory of Bowman,
or at least to show that no purely physico-chemical theory as yet
constructed will account for all the facts.
Ludwig supposed that the urine, qualitatively complete in all its
constituents, was simply filtered through the glomeruli, the work
done in this filtration being performed entirely at the expense of
the energy of the heart -beat represented as lateral pressure in the
vessels of the tufts. But as the proportion of salts, and especially
of urea, is very far from being the same in urine as in blood, it had
further to be assumed that the liquid which passes into Bowman's
capsule is exceedingly dilute, and that absorption of water, and
perhaps of other constituents, takes place in its passage along the
renal tubules. This process of reabsorption he pictured as a purely
physical diffusion between the dilute urine in contact with the free
ends of the epithelial cells lining the tubules and the much more
concentrated lymph with which their deep ends are bathed. The
great length of these tubules, as compared with those of most other
glands, might indeed seem to indicate a long sojourn of the urine
in them, and the probability of important changes being caused in
its passage along them. But if we consider the immense length
(60 to 70 cm.) of the seminal tubules and of their gigantic ducts
(epididymis 6 metres), where, of course, absorption of water on a
large scale is out of the question, it will be granted that little can
be built upon the mere length of the renal tubules. On the other
hand, the salivary glands, where there are no glomeruli, secrete as
much water as the kidneys are supposed to filter ; and the pancreas,
whose capillaries form the first of a double set, and therefore in this
respect correspond to the renal glomeruli, secretes less water than
the liver, whose capillaries correspond to the low-pressure plexus
around the convoluted tubules of the kidney. So that deductions
drawn from the anatomical relations of the bloodvessels are not in
this case of much value, unless supported by physiological results.
It is somewhat unfortunate that systematic writers have fallen
into the habit of discussing the mechanism of urinary secretion as
if the Ludwig theory and the Bowman theory presented an exact
antithesis, as if the one offered a complete ' mechanical ' explana-
tion of a process, which the other viewed as entirely ' vital,' and
therefore withdrawn from physical explanation.
We need not concern ourselves here with the historical develop-
494 EXCRETION
ment of this discussion. Three main questions require our
attention :
1. Is there any evidence that reabsorption actually occurs in the
tubules ? If reabsorption on an important scale does take place, it
follows at once that there must be a difference of function between
the two parts of the renal apparatus, through which urinary con-
stituents pass in opposite directions.
2. But if there is no reabsorption, or none of importance, it may
still be asked whether, the direction of movement of the urinary
constituents through the glomeruli and the tubular epithelium being
the same, some quantitative or qualitative difference in their
activity may not exist, certain constituents, e.g., passing mainly or
exclusively through the one or the other.
3. When these questions have been settled, we are in a position
to consider the nature of the process by which the urinary con-
stituents find their way from the blood into the lumen of the
capsules and the tubules, or, if there is reabsorption, out of the
tubules into the lymph and blood again, and to see whether or no
it can be entirely explained on mechanical and physico-chemical
principles.
The Question of Reabsorption from the Tubules. — That some
absorption can take place from the kidney when the pressure in
the ureter is abnormally raised need not be doubted, and when
substances like potassium iodide or strychnine are introduced into
the ureter or the pelvis of the kidney under these circumstances,
they can speedily be detected in the blood. When the ureter
pressure (in dogs) is only slightly increased, instead of evidence of
reabsorption, we obtain evidence of increased secretion. The
volume of urine, the total quantity of sulphate in the urine when
sodium sulphate is injected into the blood as a diuretic, and the
total amount of reducing sugar when phlorhizin is injected, are all
greater on the obstructed than on the normal side. These facts are
quite opposed to the idea that nitration and reabsorption are im-
portant factors in the preparation of normal urine (Brodie and
Cullis) . Changes in the blood-flow through the kidney have nothing
to do with the results, since the small increase in pressure in the
ureter was shown not to affect the rate of flow of the blood. The
attempt has been made to decide whether absorption normally
occurs by removing as much of the tubules as possible, and seeing
whether the character of the urine is altered. In rabbits the whole
or a large portion of the medulla has been excised from one kidney
and the other then extirpated. From the mutilated kidney two or
three times as much urine was said to flow as was secreted by a
control rabbit operated on in the same way, except for the removal
of the renal medulla (Ribbert). The conclusion was drawn that
the greater quantity of urine escaping was due to the smaller
opportunity for reabsorption of the water. But experiments men-
THE SECRETION OF THE URINE 495
tioned in Chapter XL suggest a different interpretation of these ob-
servations. And Boyd, who repeated Ribbert's work, obtained quite
different results after partial removal of the medulla. He found
it impossible to remove the whole. So that hitherto the direct
method of eliminating the tubules has left the matter where it was.
Some light has been thrown on this question, by taking advantage
of the anatomical fact that the kidney of batrachians, and, indeed,
that of fishes and ophidia as well, has a double blood-supply. The
renal artery gives off afferent vessels to the glomeruli; the vena
advehens, or renal portal vein, breaks up, like the portal vein in the
liver, into a plexus of capillaries surrounding the tubules, and there
seems to be no communication between the two vascular systems.
By tying all the arteries going to the kidneys in frogs the circula-
tion through the glomeruli can be completely cut off, while ligation
of the renal portal vein does not affect the blood-supply of the
glomeruli, though markedly interfering with that of the tubules.
Gurwitsch has found that, after ligation of the renal portal vein of
one kidney in (male) frogs, the flow of urine from that kidney is
much diminished as compared with the other. He argues that if
reabsorption of dilute urine filtered through the glomeruli takes
place in the tubules, the opposite result ought to be obtained, since
the glomeruli are not affected, while any absorptive power of the
tubules must be crippled or abolished.
Experiments on the Excretion of Pigments by the Kidney. — In
connection with the second question, and also incidentally with the
first, the results of experiments on the distribution of pigments in
the kidney after their injection into
the blood have often been appealed to.
Heidenhain injected indigo - carmine
into the blood of rabbits, and after a
variable time killed them, cut out the
kidneys, and flushed them with alcohol,
in which the pigment is insoluble. His
results were as follows: (i) When the
Fif- I9I--Diasrfn °* Distri])U- spinal cord was cut before the injec-
tion of Pigment in Kidney after ,f ., ,, ,
injection into Blood. The cor- tlon m order to reduce the blood-
tex between a and 6 and be- pressure, the blue granules were found
tween c and d was cauterized ifl the < roddecl • epithelium of the
before the injection. In the 1.1.1.1 j«
blank wedge-shaped portions, i, convoluted tubules and the ascending
there was no pigment, in the limb of Henle's loop, and in the lumen
zones shaded like 2 there was of the tubuleS, but nowhere else. '
some pigment, but no* so much -.-. i ,
as in the areas shaded like 3. Bowman s capsules contained no pig-
ment. The renal cortex was coloured
blue. (2) When the spinal cord was not cut, the pigment was found
in the medulla and pelvis of the kidney, as well as in the cortex,
but always in the lumen of the tubules, and not in the epithelium,
except in the situations mentioned. (3) If a portion of the cortex
496 EXCRETION
of the kidney had been cauterized with nitrate of silver before in-
jection of the pigment, the spinal cord being left intact, a wedge of
the renal substance, corresponding to this area, remained coloured
only in the cortex, although the rest was blue in the medulla
also. The ' rodded ' epithelium was filled with blue granules as
before (Fig. 191).
(i) shows that the epithelium is capable of excreting some sub-
stances at least. (2) appears to show that when the blood-pressure
is normal water is poured out from some part of the tubule, and
washes the pigment separated by the ' rodded ' epithelium down
towards the papillae. (3) suggests that it is through the glomeruli
that most of the water passes. For cauterization has not destroyed
the power of the epithelium to excrete pigment, and therefore,
presumably, would not have destroyed its power to excrete water
if it possessed this power in any great degree; and the glomeruli
and their capsules are the only other part of the renal mechanism
which can have been affected. It must be carefully noted that
these experiments do not prove that urea is secreted by the tubular
epithelium. Indeed, after section of the cord no accumulation
of urea takes place in the kidney (Cushny). It would be equally
erroneous to conclude from this that the cells of the tubules do not
secrete urea. For the reduction of the blood-supply may have
rendered them incapable of doing so.
When pigments are injected into the dorsal lymph- sac of a frog
without interference with the renal circulation, they are found
plentifully in the lumen of the convoluted tubules, and also in the
epithelial cells lining them. The suggestion has been made that
the pigments have been absorbed by the cells from the lumen, and
not excreted by them into it. And certainly pigments soluble in
the cytoplasm or in the substances that form the envelopes of cells,
and therefore capable, like methylene blue, of staining them during
life, might be taken up by the renal epithelium if excreted into the
tubules by the glomeruli, and might cause staining of them, par-
ticularly, of course, of the free ends of the cells next the lumen.
But this suggestion is inadmissible, since, on injection of the same
pigments after ligation of the renal portal vein, the convoluted
tubules contain little or no pigment in their lumen. And when the
urinary flow is stopped on one side in mammals by temporary com-
pression of the renal artery, the corresponding kidney takes up fully
as much carmine as its fellow (Carter). There is no doubt that not
only pigments capable of ' vital staining,' like methylene blue, but
also pigments which do not stain living cells, are taken up from
the blood (or lymph) by the epithelial cells, and, lying in vacuoles
in their cytoplasm, are transported towards the lumen, and there
extruded. It is not the solubility of the pigments in lipoids, and
therefore their solubility in the supposed lipoid envelope of the cells,
which determines whether they shall be excreted. The degree in
THE SECRETION OF THE URINE 497
which they are capable of being presented to the cells in non-colloid
solution appears to some extent to be a determining factor. The
pigments not taken up are highly colloidal (Gurwitsch, Hober).
Shafer has recently confirmed Heidenhain's statements as to the
place of excretion of indigo-carmine. When leuco-indigo-carmine
(a colourless reduction-product of indigo-carmine) was injected, the
blue oxidized substance was found in the lumen of the convoluted
tubules and in the collecting tubules, but not at all in the Bow-
man's capsule. The cells of the convoluted tubules were colour-
less, because they kept the pigment in its reduced condition, and it
only became oxidized in the lumina of those parts of the tubules
whose contents, according to Dreser, show an acid reaction. On oxi-
dation by peroxide of hydrogen the cells of the convoluted tubules
became faintly green, but the Bowman's capsule remained colourless.
This can only be explained on the assumption that the leuco-product
of the pigment was excreted by the cells of the convoluted tubules.
But these cells are far from taking up all pigments indifferently.
Some pigments are extruded mainly by one part, others mainly by
another part, of the renal tubule, and some even by the glomeruli,
as shown long ago for ammonium carminate. The glomeruli, how-
ever, are in general far less active in this regard than the epithelial
cells, and the fact that the latter pick out from the blood such sub-
stances as these foreign pigments, which pass through the Mal-
pighian tufts unchallenged, renders it likely that the tubules also
exercise a special function in the secretion of the normal con-
stituents of urine. More direct evidence of this is not wanting,
for Bowman saw crystals of uric acid in the epithelium of the
convoluted tubules of birds. Heidenhain found that urate of soda
injected into the blood of a rabbit is excreted by the epithelium of
the convoluted tubules and the ascending part of Henle's loop,
just as is the case with indigo-carmine. And Nussbaum's experi-
ments, although not quite conclusive, have made it probable that
in the frog urea is actually separated by the epithelium of the
tubules. They were founded on the anatomical peculiarity in the
renal circulation of the frog already mentioned. By tying the renal
arteries in that animal, he thought he could at will stop the circula-
tion in the glomeruli, and he found that after this was done there
was no further spontaneous secretion of urine. But when urea was
injected intravenously the secretion of urine again began, urea
being eliminated by the kidneys, and water along with it. Sugar;
peptone, and egg-albumin, injected into the blood, no longer passed
into the urine, even when the secretion was excited by simultaneous
injection of urea, although they readily did so when the arteries
were not tied. He concluded that the Malpighian corpuscles have
the power of excreting water, sugar, peptone, and albumin, while
the epithelium of the tubules excretes urea as well as water.
Beddard has confirmed Nussbaum's statement that when all th
32
49& EXCRETION
arteries going to the kidney are tied the glomeruli are completely
and permanently deprived of blood. The spontaneous secretion
of urine is totally stopped, as Nussbaum found, but only in three
experiments out of eighteen was it possible to start the secretion
by injection of urea. The epithelium of the tubules degenerated
and desquamated after complete ligation of all the renal arteries,
showing that it requires some arterial blood as well as the venous
blood from the renal portal to maintain its vitality. The degenera-
tion of the epithelium can be prevented by keeping the frogs in an
atmosphere of oxygen after ligation of the arteries. In six such
frogs, in which the complete elimination of the glomeruli was con-
trolled by subsequent injection, secretion of urine followed the
injection of urea, alone or in combination with dextrose, phlorhi/dn,
or di-sodium hydrogen phosphate (Na2HPO4) . In all the cases the
urine contained urea, chlorides, and sulphates, and was acid to
phenolphthalein. In one case after injection of urea and dextrose,
and in another after urea and phlorhizin, the urine reduced Fehling's
solution, and therefore presumably contained dextrose (Beddard
and Bainbridge). When the frog's kidney is perfused in situ with
oxygenated salt solution a certain flow of urine takes place. Sub-
stitution of non-oxygenated saline markedly slows the flow (Cullis).
Apparently, then, the tubules have the capacity to secrete prac-
tically all the constituents of urme, and when the flow of urine is
small, probably most of it comes from the tubules. When, as in
the diuresis produced by salt solutions, large quantities of water
and salts have to be rapidly excreted, the bulk of the liquid comes
from the glomeruli, but also by a process of secretion.
Lindemann has endeavoured to exclude the glomeruli in mam-
mals by injecting oil through the renal artery. After a short time,
according to him, the oil emboli clear away from practically all
parts of the kidney except the glomeruli, which remain plugged.
If indigo-carmine be subsequently injected into the blood, it is not
only taken up from it by the embolized kidney as well as by a normal
one, but is excreted. The quantity of urine is much diminished,
and its specific gravity increased, but its composition is not essen-
tially altered. He infers that the tubules are in a high degree
independent of the glomeruli as an apparatus for the secretion of
urine. More conclusive observations have lately been reported in
which the tubules were eliminated by producing an artificial nephritis
in rabbits by the subcutaneous injection of sodium tartrate. Tar-
trates act mainly upon the tubules, causing no, or a much smaller,
effect upon the glomeruli. After the intravenous infusion of a
solution containing sodium chloride and urea during pronounced
tartrate nephritis, all the chlorine appears in the urine within forty-
eight hours, but little, if any, of the urea. In the light of the
histological findings, this is interpreted to mean that under normal
conditions chlorides and water are passed through the glomerular
THE SECRETION OF THE URINE 499
mechanism, and urea through the convoluted tubules (Underbill,
Wells, and Goldschmidt) . These results constitute a direct and
striking confirmation of the Bowman hypothesis.
As regards our first two questions, we may conclude that there is
no good evidence that reabsorption of water or other constituents of the
urine in the renal tubules plays an important part in the preparation
of that secretion. Many facts favour the conclusion that the glomeruli
and the renal epithelium act as distinct, although, of course, mutually
supplementary mechanisms, the glomeruli separating the larger portion
of the water and salts, the epithelium the larger portion, if not the
whole, of the characteristic organic constituents.
As regards the third question, it is now generally admitted, even
by those who uphold a modified ' mechanical ' theory, that if
the urine is originally separated from the blood by filtration at the
expense of the energy of the heart-beat represented by the pressure
of the blood in the glomeruli, the reabsorption in the tubules cannot
be attributed to simple diffusion, but must be a selective process
analogous to absorption in the intestine and entailing the expendi-
ture of a large amount of work at the expense of the food materials
or the protoplasm of the epithelial cells. Every attempt at a
strictly mechanical explanation breaks down for the kidney, as for
other glands.
The practical absence from urine of the proteins and sugar of the
blood under normal circumstances, and the elimination by the
kidney of egg-albumin, peptone, and other bodies when injected
into the veins, show a selective permeability inexplicable by refer-
ence to any known structural or physico-chemical property of the
renal epithelium or the glomeruli, but precisely the kind of thing
which the physiologist has, without being hitherto able to explain
it, learnt' to associate with the activity of living cells. Urea and
dextrose, both highly diffusible substances, circulate side by side
in the bloodvessels of the kidney. The one is taken and the other
left. The urea is a waste-product of no further use in the economy.
The sugar is a valuable food-substance. The kidney selects with
unerring certainty the urea, of which only 4 parts in 10,000 are
present in the blood, but rejects the sugar, of which there is three
times as much. The theory that the dextrose of the blood or a
part of it is combined with substances in the colloid state, and not
in ordinary solution, has been advanced from time to time as an
explanation of the practical impermeability of the kidney for this"
sugar under normal conditions. But no proof of the truth of this
hypothesis has ever been given. On the contrary, there is good
evidence that all the dextrose which is estimated in blood by
analytical methods is in the free condition. For instance, dextrose
easily escapes from blood circulating in the vivi-diffusion apparatus
previously described (p. 48). And when the plasma of shed blood is
placed in a dialyser tube of animal membrane surrounded by a liquid
5oo EXCRETION
in which dextrose is dissolved in exactly the same concentration as
that determined in the plasma by the ordinary chemical methods,
the contents of the dialyser neither lose nor gain dextrose. Now,
the plasma ought to gain sugar by diffusion if a portion of the
dextrose in it exists in a combination which prevents its diffusion,
just as it does gain dextrose when the liquid outside the dialyser
contains sugar in greater concentration than the plasma (Michaelis
and Rona).
Egg-albumin injected into the blood passes through the renal
circulation side by side with the serum-albumin of the plasma.
Both are indiffusible through membranes, and to the physical
chemist the differences between them may appear superficial and
minute. But the kidney does not hesitate for an instant. A large
part of the egg-albumin is promptly excreted as a foreign substance ;
the serum-albumin passes on untouched.
Not only does the kidney exercise a power of qualitative selec-
tion; it also takes cognizance of the quantitative composition of
the blood. So long as there is less sugar in the plasma than about
1-5 to 2 parts in 1,000, it is refused passage into the renal tubules.
But when this limit is passed, and the proportion of sugar in the
blood becomes excessive, the kidney begins to excrete sugar, and
continues to do so till the balance is redressed.
The advocates of the theory of filtration through the glomeruli
under the influence of the difference of hydrostatic pressure in the
capillaries and in the lumen of the capsules have made their firmest
stand on the excretion of the inorganic constituents of the urine.
They have laid stress particularly on the fact that the hydraemic
plethora caused by intravenous injection of salts is accompanied
by diuresis. It is true that the direct introduction of water into
the blood, or its attraction from the lymph-spaces when the osmotic
pressure of the blood is increased by the injection of substances like
urea, sugar, and sodium chloride, may cause a condition of hydrcstnic
plethora, and that this plethora may sometimes be associated with
an increase of pressure in the capillaries in general, and therefore
in the vessels of the Malpighian tuft. It may also be admitted that
such an increase of pressure might be accompanied by an increased
filtration of water and salts into Bowman's capsule. Even in the
excised kidney, after the vital activity of its cells may be presumed
to have ceased, filtration of the most varied solutions occurs when
the organ is perfused with them through the renal artery. The
liquid which escapes from the ureter always has the same composi-
tion as the perfusion fluid (Sollmann). It would certainly appear
unlikely that the glomerular epithelium should make no use what-
ever for the furtherance of its task of the difference of hydrostatic
pressure on its two surfaces. It is in taking advantage of such
circumsta ces for the promotion of its specific work up to the
point at which they cease to favour it that a great part of the true
THE SECRETION OF THE URINE 501
secretory activity of cells may be supposed to consist. When we
see a barge passing through a lock, and being gradually lifted to
the proper level by the inrush of water, we never dream of saying
that the whole thing is an affair of the laws of hydrostatics. We
know that the part played by the lock-keeper, the opening and
closing of the gates and sluices at the proper time, is all-important,
although he does not lighten by one ounce the weight which the
water must lift. He uses the head of water for a specific purpose
— namely, to lift the barge. In like manner it is to be expected
that the glomerular epithelium, when the difference of pressure
on its two surfaces is increased by hydraemic plethora, will use the
increased facility of nitration to rapidly excrete a portion of the
water. But who will believe that the addition of a tumbler of
water, absorbed from the alimentary canal, to 4 or 5 litres of blood
circulating in a system of vessels whose capacity can and does vary
within wide limits, should cause in the capillaries of the kidney
an increase of pressure exactly proportional to the increase in the
elimination of water in the urine, lasting for the sarne time and
disappearing at the moment when the normal composition of the
blood is restored ? Nor is it easier to explain on any mechanical
hypothesis how it is that in a starving animal the quantity of
inorganic substances eliminated in the urine drops almost to zero,
while the proportional amount in the blood and tissues is little, if
at all, affected. In a rabbit rendered poor in sodium chloride by
feeding it with salt-free food, the injection of a solution of sodium
chloride isotonic with the blood produces no diuresis for a con-
siderable time, but, on the contrary, a diminished flow of urine,
while a similar solution injected into the veins of a rabbit previously
fed with salted food causes an immediate and considerable diuresis.
When small quantities of isotonic solutions of various salts are
injected, those not normally present in the blood produce a greater
diuresis than normal constituents. Sodium chloride, which is
present in normal plasma in greater amount than any other salt,
causes the smallest diuresis of all (Haake and Spiro).
Such facts suggest that the secreting cells of the kidney are stimu-
lated or inhibited by the contact of blood or lymph in which the
normal constituents are present in too great or in too small amount,
and that the intensity of the action is proportional to the degree of
deficiency or excess. The greater the velocity of the circulation
in the kidney, the more effective will be the stimulation produced"
by any given substance present in excess, and therefore the greater
the total amount of it eliminated in a given time. For in making
the round of the renal circulation the concentration of the sub-
stance in any given portion of blood will fall less, and therefore the
average stimulation exerted by it during the round will be greater
the faster the blood flows. It is quite in agreement with this that
when plethora is occasioned by transfusion of blood there is little
502 t EXCRETION
or no diuresis, although the increase of arterial, capillary, and
venous pressure, and the dilatation of the kidney, are evident.
For the rapid passage of liquid out of the vessels would lead to a
great increase in the relative proportion of corpuscles to plasma —
that is to say, to an abnormal condition of the blood. On the other
hand, when plethora is produced by injection of serum diuresis
occurs (Cushny). This, again, is what we should .expect, since the
elimination of the superfluous liquid will restore the normal pro-
portion. The diminished viscosity of the blood (p. 23) produced
by the excess of serum will aid the flow through the kidney and
therefore increase the diuresis, while in the case of the plethora
produced by injection of blood the elimination of liquid will at once
increase the viscosity, diminish the velocity of the renal flow, and
tend to lessen diuresis.
There is, then, little more reason to assume that the copious flow
of urine which follows the absorption of a large quantity of water
is due to a mere process of filtration than there is to believe that
nitration, and not selective secretion, is the cause of the gush
of saliva which precedes vomiting, or the sudden outburst of
sweat on sudden and severe exertion. In addition, there are the
positive proofs already mentioned that the ' rodded ' epithelium
of the tubules, which no one supposes to be abandoned more
to mere physical influences than the epithelium of the salivary
glands, plays a part in the secretion of some of the urinary
constituents.
Cushny has recently stated more clearly than had previously been
done a theory which he designates as the ' modern theory ' of urine
formation. He assumes that blood-plasma is filtered through the
glomeruli under the hydrostatic pressure of the blood, only the colloid
proteins being kept back. The filtrate contains the non-colloid con-
stituents approximately in the proportions in which they exist in
plasma. It is therefore very poor in urea and very rich in sugar as
compared with urine. In the tubules some of the constituents, which
he terms ' threshold bodies ' are reabsorbed. These are the sub-
stances like sugar, the sodium and chlorine ions, etc., which are only
excreted when they exceed a certain threshold value in the plasma.
Other constituents of the filtrate, like urea, are not reabsorbed. These
are called 'no-threshold bodies,' and are excreted in proportion to
their absolute amount in the plasma. The cells of the tubules are
supposed in some way at present unknown to take up from the filtrate
the threshold bodies, and always in a definite concentration — namely,
that in which they normally exist in blood. As Cushny puts it, the
filtrate is deproteinized plasma, from which ' Locke's fluid ' (p. 66)
is reabsorbed by the tubule cells. Apparently he thinks it simpler to
make the assumption that the renal cells are organized to absorb from
the lumen of the tubules a solution of invariable composition, leaving
a variable residue to be excreted, than to make the assumption, under-
lying the Bowman-Heidenhain theory, that they are organized to
leave behind in the blood or lymph an invariable residue by absorbing
from them a solution of variable composition. In reality, however, the
two assumptions are precisely on the same footing : they are equally
THE SECRETION OF THE URINE 503
simple or equally abstruse. For a cell which is able to take up
' Locke's fluid ' from a deproteinized plasma is able in that very act
to reject any constituent which does not belong to 'Locke's fluid,'
as well as an excess of any constituent which does belong to it. What is
rejected and its amount are quite as important, if the final product is
to be constant, as what is accepted and its amount. If we are willing
to attribute a power of this kind to the free end of a tubule cell we
need not shrink on the ground of added complexity from investing
the attached end of the cell with the power of refusing passage to
' Locke's fluid ' from the plasma or the lymph while accepting crys-
talloid constituents like urea which do not belong to it, as well as an
excess of any constituent which does belong to it. There is nothing
more ' occult ' about a cell which bars out sodium chloride till it
exceeds 0-9 per cent, in the fluid offered to it, and then lets the surplus
through, than there is about a cell which takes up sodium chloride
from the fluid offered to it till it has amassed a concentration of 0-9
per cent., and then bars out the surplus.* In like manner, the financial
organization required by a Government to take from a citizen in taxes
the surplus of his income above one hundred pounds would be of the
same general nature as that required to take from him his whole income,
returning him one hundred pounds to live on. If a machine could
manage the one operation, a mandarin would not be needed for the other.
It is impossible in this place to go further into the discussion of the
reabsorption theory so ably presented by Cushny. In the absence of
definite evidence of reabsorption on the great scale required by the
theory, it remains simply a working hypothesis, which is all that can
be claimed at present for any theory of urine formation. One of the
objections always urged against filtration (with reabsorption) theories
has been the enormous amount of liquid which must under certain con-
ditions be poured into the renal tubules. Heidenhain calculated that
in a man no less than 70 litres of liquid per day must be filtered through
the glomeruli in order that the urea found in the urine may be obtained
from a glomerular filtrate containing 0-05 per cent, of urea. This is
probably a moderate estimate, and considerably larger amounts of
nitrate in proportion to body and kidney weight have been deduced
from data obtained in animals. It has been argued by advocates of
the reabsorption theory that equally great quantities of lymph con-
taining urea in the small concentration in which it exists in the plasma
must be poured out around the attached ends of the tubule cells on
the hypothesis of direct secretion. This argument, however, is based
upon an erroneous conception of the manner in which exchange between
the blood and the tissues proceeds. There is no reason to suppose"
* The reabsorption theory is perhaps inferior to the ' direct secretion '
theory in one point. If a solution of constant composition is always absorbed
from the glomerular nitrate, the smaller the concentration in the filtrate of
any substance capable of being taken up by the cells, the greater will be the
proportion of it absorbed; and the greater its concentration in the filtrate,
the smaller will be the proportion of it absorbed. On the direct secretion
theory, the greater the concentration of a substance in the blood or lymph
in contact with the cells, the more of it will pass into the cells and be ex-
creted by them. The ' modern ' theory which sets out by saying to the
Bowman-Heidenhain theory, ' Stand by thyself, come not near to me, for I
am more physical than thou,' thus abandons a physical process, diffusion,
which its rival utilizes. The fact is that the simplification attained by postu-
lating filtration as the first stage in urine formation has to be paid for in
the reabsorption. The boat having shot the rapids in the glomeruli with
next to no physiological expense has straightway to be more or less painfully
locked a certain distance upstream.
504 EXCRETION
that the exchange between blood and tissue lymph is mainly accom-
plished by nitration from the capillaries of vast quantities of liquid
containing the crystalloid constituents and the gases in the concen-
tration in which they exist in plasma. On the contrary, the dissolved
substances are currently and no doubt correctly assumed to move to
a great extent by diffusion through the capillary walls (perhaps with
a certain amount of active intervention of the endothelial cells) and
across the thin sheets of tissue lymph on their way to and from the
cells. In other words, they move mainly through the water and not
with the water. An attempt to explain the gaseous exchange between
the blood and the tissues as a matter purely of nitration of plasma
containing dissolved gases, and not at all of diffusion of the gases,
would lead to curious results. There is no more reason to believe that
urea passes from the blood to the boundary of the tubule cells by a
filtration process independent of diffusion, and therefore entailing the
irrigation of the cells with a very large amount of lymph, than there
is to believe that when 100 c.c. of arterial blood loses 10 c.c. of oxygen
in passing through the capillaries, this is accomplished by filtration
into the lymph spaces of 4,000 c.c. of plasma containing 0-25 c.c. of
oxygen in 100 c.c. (p. 252).
As to the nature of the mechanism set in motion, and the series
.of events that take place as the constituents of the urine journey
from the interior of the bloodvessels to the lumen of the tubules,
we know no more than in the case of other glands. This alone
is clear, that the separation of the urine from the blood implies the
performance of a large amount of work by the kidney. A token of
the intensity of the metabolic effort required is the marked increase
in the absorption of oxygen which occurs during diuresis. In one
experiment the oxygen absorbed by a dog's kidneys was n per cent,
of what would have been used up by the entire animal under normal
conditions.
The mere fact that urine differs in its quantitative composition
from blood-plasma is sufficient to show that work must be done in
its separation from the blood. Although the amount of work
cannot be calculated from the difference in the osmotic pressures
of the two liquids, a comparison of the freezing-points affords quali-
tative evidence of the performance of work by the kidney. For
average urine, the value of A is several times as great as for the
plasma. Blood-plasma freezes at - 0-55° to - 0-65° C. (average,
- 0-6°, corresponding to an osmotic pressure of 5,662 mm. of mercury,
or about 75 metres of water). Human urine has been found to
freeze at -1-38° to -2»ii°C. (average, - i«8° C., corresponding to
an osmotic pressure of about 17,000 mm. of mercury, or 225 metres
of water). For highly concentrated urines, the depression of the
freezing-point may be considerably greater. Even when the
freezing-point is found in very dilute urines to be approximately
the same as in the blood-plasma, work may still have been done in
the separation of the urine, because although the total molecular
concentration may be the same in the two liquids, the concentra-
tion of each of the substances in solution may be different. For
THE SECRETION OF THE URINE 505
example, even in the most dilute urine, the concentration of urea
will in general be much greater than in the blood. It is of interest
in connection with the work performed by the kidney that when
the flow of urine is increased by diuretics like caffeine or sodium
sulphate, which cause the secretion of urine with a very different
crystalloid composition from that of the plasma, more oxygen is
used up, whereas the diuresis caused by the injection of Ringer's solu-
tion where the urine and plasma do not differ materially in the amount
or kind of the non-protein constituents, is accomplished practically
without change in the oxygen consumption of the kidney.
Significance of the Glomeruli. — What is the significance of the
peculiar arrangement of the glomerular bloodvessels, if the epithelium
of the capsules has secretive powers like that of ordinary glands ?
It is difficult to believe that these unique vascular tufts have not a near
and important relation to the renal function; but it is by no means
clear what that relation is. The secretion of water, and even its rapid
secretion, is not at all bound up with any set arrangement of blood-
vessels. Gland-cells all over the body secrete water under the most
varied conditions of blood-pressure, although a comparatively high
pressure is upon the whole favourable to a copious outflow.
But the kidney has perhaps other functions than excretion
(Chapter XI.). And it may be that the simplest part of the latter
process, the elimination of water and salts, is largely thrown upon the
Malpighian corpuscles, as a physiologically cheaper machine than the
epithelium of the tubules, which is left free for more complex labours.
These may include not only the separation of nitrogenous metabolites,
but also synthetic processes possibly concerned in the regulation of
protein metabolism. One characteristic synthesis, the union of benzoic
acid and glycin to hippuric acid, has already been referred to. As will
be shown later (p. 580), it takes place mainly, in some animals perhaps
exclusively, in the kidney. The epithelium of the glomerulus, being a
less highly organized and less delicately selective mechanism than that
of the convoluted tubules, may more easily respond to increase of blood-
pressure by increased secretion. At the same time, placed as it is at
the last flood-gate of the circulation, where the escape of anything
valuable means its total loss, the glomerular epithelium may be endowed
with a general power of resistance to transudation, which renders a
comparatively high blood-pressure a necessary condition of its acting
at all. And as a matter of fact water ceases to be secreted by the
kidney long before the blood-pressure in the glomeruli can have fallen
below that which suffices for the highest activity of the liver. Perhaps,
however, the high minimum pressure required (30 to 40 mm. of mercury
in the dog) is merely the necessary consequence of the long and difficult
path which most of the blood going through the kidney has to take, and,
that a sufficient blood-flow cannot be kept up with less. It may be,
too, that the comparatively small surface of the glomeruli, restricted
in order to leave room for the more highly organized parts of the renal
mechanism, entails the more intense and concentrated activity which
the high blood-pressure renders possible, and the simplicity of work
and organization renders harmless.
An obvious result, and perhaps an important one, of the peculiar
arrangement of the bloodvessels of the kidney is that the renal tubules
proper are shielded from an excessive blood-pressure by the inter-
position of the glomeruli as a block. This may be either because the
epithelium of the tubules would not perform its work so well under a
5o6 EXCRETION
high blood-pressure, or because there would be a danger of substances
which ought to be retained being cast out into the urine. In this con-
nection it is interesting to note that the specific constituents of urine
are separated by epithelium surrounded by capillaries of the second
order, and therefore with a smaller blood-pressure than exists in the
capillaries of most glands, while the same is true of bile, anothcf
(practically) protein-free secretion.
The maximum secretory pressure in the kidney, as shown by a
manometer tied into the divided ureter, is about 60 mm. of mercury
in the dog, or less than half that of saliva. If the escape of the
urine is opposed by a greater pressure than this, or if the ureter is
tied, the kidney becomes cedematous. Whether the oedema is due
to reabsorption of urine or to the pouring out of lymph owing to
the pressure of the dilated tubules on the veins has not been de-
finitely settled. It has been already pointed out that there is no
necessary relation between the blood-pressure in the capillaries of
a gland and its secretory pressure; and, so far as this goes, water
might just as well be secreted at a pressure of 60 mm. of mercury
from the low-pressure blood of the second set of renal capillaries
as from the high-pressure blood of the glomeruli. By obstruction
the molecular concentration of the urine is diminished to half or
three-quarters of the normal.
The Influence of the Circulation on the Secretion of Urine. —
Although the activity of no organ in the body is governed more
by the indirect effects of nervous action than that of the kidney,
no proof has been given of the existence of secretory fibres for it
comparable to those of the salivary glands. All the changes in the
rate of renal secretion which follow the section or stimulation of
nerves can be explained as the consequences of the rise or fall of
local or general blood-pressure, and of the corresponding variations
in the velocity of the blood in the renal vessels.
The best way to study variations in the calibre of the renal vessels is
the plethysmographic method, and the oncometer of Roy is a plethysmo-
graph adapted to the kidney (Fig. 192). It consists of a metal capsule
lined with loose membrane, between which and the metal there is a
space filled with oil. The two halves of the capsule open and shut on a
hinge ; and the kidney, when introduced into it, is surrounded on all
sides by the membrane, the vessels and ureter passing out through an
opening. The oil-space is connected with a cylinder also filled with oil,
above which a piston, attached to a lever, moves. The lever registers
on a drum the changes in the volume of the kidney — i.e., practically the
changes in the quantity of blood in it, and therefore in the calibre of
its vessels. A still better oncometer is that of Schafer, in which air is
employed instead of oil.
Nerves of the Kidney. — Both vaso-constrictor and vaso-dilator fibres
for the renal vessels, but most clearly the former, have been shown
to leave the cord (in the dog) by the anterior roots of the sixth thoracic
to second lumbar nerves, and especially of the last three thoracic.
They run in the splanchnics, and then through the renal plexus — around
the renal artery — into the kidney. The vaso -constrictors predominate,
THE SECRETION OF THE URINE
507
so that the general effect of stimulation of the nerve-roots, the splanch-
nics, or the renal nerves is shrinking of the kidney, with diminution or
cessation of the secretion of urine. But slow rhythmical stimulation
of the roots causes increase of volume, the scanty dilators being by this
method excited in preference to the constrictors.
The renal nerves, entering at the hilum, branch repeatedly, so as to
form a wide-meshed plexus around the arteries, and accompany them
even to their finest ramifications in the cortex. Coming off from the
nerves surrounding the arteries are fine fibres which are distributed to
the convoluted tubules. Some of them terminate in globular ends,
others in fine threads that pass through the membrana propria (Berkely).
Section of the renal nerves is followed by relaxation of the small
arteries in the kidney, and consequent swelling of the organ. The
flow of urine is greatly increased, and sometimes albumin appears
in it, the excessive pressure in the capillaries (particularly in those
of the glomeruli) being
supposed to favour the
escape of substances to
which a passage is refused
under normal conditions.
An experiment which is
sometimes quoted as a de-
cisive test of the relative
importance of changes in
the rate of flow, and in
the pressure of the blood
within the glomeruli, is
that of tying the renal
Fig. 192. — Diagram of Organ-Plethysmograph or
Oncometer. B, metal box in two halves open-
ing on the hinge H ; M, thin membrane ; A, space
filled with oil; O, organ enclosed in oncometer;
V, vessels of organ; t, tube for filling instrument
with oil; T, tube connected with D, which opens
into cylinder C ; C is also filled with oil ; P, pis-
ton attached by E to a writing lever.
vein. This undoubtedly
does not lower the intra-
glomerular pressure — on
the contrary, it must in-
crease it — -but the secretion of urine stops. If the venous outflow
from the kidney is only partiallyinterfered with, the flow of urine is
immediately diminished, but the administration of a diuretic like
potassium nitrate causes an increase. It is more than likely that
in these experiments the secretion stops or slackens not because a
high blood-pressure, but because an active circulation is its necessary
condition. When the blood stagnates in the kidney the natural
stimulus to the renal apparatus speedily disappears owing to the
elimination of the urinary constituents to the neutral or indifferent
point (pr 501). The experiment, however, is not perfectly conclu-
sive. For few glands can go on performing their function after the
circulation has ceased. The kidney must be able to feed itself in
order to continue its work. Above all, it ne'eds oxygen; and it
might be urged that if the blood in the glomeruli could be kept at
the normal standard of arterial blood, secretion might still go on
after ligation of the renal vein.
so8 EXCRETION
According to Ludwig, indeed, the flow of urine stops, in spite
of continued nitration through the glomeruli, because the swelling
of the veins in the boundary layer compresses the tubules, and may
even obliterate their lumen. There is no conclusive experimental
evidence, however, and no a priori probability, that the obstruction
so produced is sufficiently sudden or sufficiently complete to cause
instant and total cessation of the flow. It is even less justifiable
to conclude from the experiment that the liquid part of the urine
is, at any rate, not separated by the epithelium of the tubules, since
the blood-pressure in the capillaries around the tubules must rise
very greatly after ligature of the vein, and yet secretion is stopped.
It might equally well be argued that the renal epithelium normally
secretes water under a low blood-pressure, but is disorganized under
the excessive and entirely unaccustomed pressure which follows the
closure of the vein.
It is not only through nerves directly governing the calibre of the
vessels of the kidney that the rate of urinary secretion can be
affected. Any change in the general blood-pressure, if not counter-
acted by, still more if conspiring with, simultaneous local changes
in the renal vessels, may be followed by an increased or diminished
flow of urine ; and the law which explains all such variations, or at
least serves to sum them up, is that in general an increase in the
rate of the blood-flow through the kidney is followed by an increase in
the rate of secretion. It will be remarked that this is the converse
of the great law, of which we have already seen so many illustra-
tions, that functional activity increases blood-flow. It is probable
that this law holds for the kidney as well as for other organs, but
that the influence of activity on blood-supply is subordinated to
that of blood-supply on activity, while in most tissues, as in the
muscles, the opposite is the case. It is evident that an increase in
the blood- flow would favour the secretory activity of the renal cells,
since the average concentration of the blood presented to them as
regards those constituents which they select would remain relatively
high in its circuit through the kidney. The ' stimulus ' to secretion
would, therefore, be relatively intense.
Destruction of the medulla oblongata (i.e., of the vaso-motor
centre), or section of the cord below it, diminishes the secretion of
urine, because the arterial pressure is lowered so much as to over-
compensate the dilatation of the renal vessels, which the operation
also brings about. If the blood-pressure falls below 40 mm. of
mercury, the secretion is abolished. Stimulation of the medulla or
cord also lessens the flow of urine by constricting the arterioles of
the kidney so much as to over-compensate the rise of general blood-
pressure, caused by the constriction of small vessels throughout the
body.
If the renal nerves have been cut, stimulation of the medulla
THE SECRETION OF THE URINE 599
oblongata increases the urinary secretion, because now the rise of
general blood-pressure is no longer counterbalanced by constriction
of the renal vessels. An increase in the urinary flow can be pro-
duced in the rabbit by a lesion in a part of the funiculi teretes,
which can be reached in the floor of the fourth ventricle (Eckhard),
perhaps by destroying the portion of the vaso-motor centre governing
the renal nerves, while the rest remains uninjured, or is even stimu-
lated, and thus keeps up or even increases the general blood-
pressure. There is either no glycosuria, or it is very slight.
Section of the splanchnic nerves causes a fall of arterial pressure,
which is, however (in animals like the dog, in which compensation
soon takes place), more than balanced by the simultaneous dilata-
tion of the renal vessels, and therefore for some time the flow of
urine is increased, but not so much as when the renal nerves alone
are cut. In the rabbit there is no increase. On the other hand,
stimulation of the splanchnics stops the urinary secretion, because
the general rise of pressure is not enough to make up for the con-
striction of the renal vessels.
Diuretics are substances that increase the flow of urine. Some of
them act mainly on the circulation, as by increasing the general blood-
pressure, others mainly by a direct influence on the secreting mechanism.
Digitalis is a representative of the first class ; urea and caffein belong to
the second. The action of digitalis is to strengthen the beat of the
heart, which is at the same time somewhat slowed, and to constrict the
arterioles. Both effects contribute to the increase of pressure. The
accompanying diuresis, seen practically only in cardiac disease with
dropsical effusions, is due to the improvement of the renal circulation
and the absorption of the oedema fluid. Caffein, when injected into the
blood, affects the pressure but little. It causes dilatation of the renal
vessels after a passing constriction, and an increase in the flow of urine
after a temporary diminution. The vascular dilatation is not the
chief reason for the diuretic effect, for the latter is still obtained when the
vaso-motor mechanism has been paralyzed by chloral hydrate, and
even after the secretion of urine has been stopped by the fall of pressure
consequent on section of the spinal cord. Caffein, therefore, acts
directly on the renal epithelium. When these cells are asphyxiated by
temporary clamping of the renal artery, caffein after removal of the
clamp causes no diuresis, while the injection of Ringer's fluid still
causes a secretion of urine possessing the same crystalloid composition
as the plasma, just as it would have done if perfused through the excised
kidney. The action of urea, potassium nitrate, and saline diuretics
such as sodium sulphate is probably also a direct action on the secret-
ing structures, although some have supposed that their primary effect
is to cause vaso-dilatation in the kidney.
Summary. — Our knowledge of renal secretion may be thus
summed up: The water and salts of the urine are chiefly separated
by the glomeruli ; the process is not a mere physical filtration, but
a true secretion. Substances like sugar, peptone, egg-albumin, and
hemoglobin, when injected into the blood, are probably excreted mainly
by the glomeruli ; and so is the sugar of diabetes. Urea, uric acid,
and presumably the other organic constituents of normal urine, with
510 EXCRETION
a portion of the water and salts, are excreted by the physiological
activity of the ' rodded ' epithelium of the renal tubules. The rate of
secretion of urine rises and falls with the pressure, and still more with
the velocity, of the blood in the renal vessels. No secretory nerves for
the kidney have been found ; the effects of section or stimulation of
nerves on the secretion can all be explained by the changes produced in
the renal blood-flow. Some diuretics act by increasing the blood-flow,
others directly on the epithelium of the tubules or the glomeruli.
SECTION III. — EXPULSION OF THE URINE.
Micturition. — -The urine, like the bile, is being constantly formed;
although secretion varies in its rate from time to time, it never
ceases. Trickling along the collecting tubules, the urine reaches
the pelvis of the kidney, from which it is propelled along the ureters
by peristaltic contractions of their walls, and drops from their valve-
like orifices into the bladder. When this becomes distended, rhyth-
mical peristaltic contractions are set up in it, and notice is given
of its condition by a characteristic sensation, which is perhaps aided
by the squeezing of a few drops of urine past the tonically con-
tracted circular fibres that form a sphincter round the neck of the
bladder, and into the first part of the urethra. The desire to empty
the bladder can be resisted for a time, as can the desire to empty
the bowel. If it is yielded to, the smooth muscular fibres in the
wall of the viscus are thrown into contraction. This is aided by an
expulsive effort of the abdominal muscles. The sphincter vesicae
is relaxed; and the urine is forced along the urethra, its passage
being facilitated by discontinuous contractions of the ejaculator
urinae muscle, which also serve to squeeze the last drops of urine
from the urethral canal at the completion of the act.
Regurgitation into the ureters is to a great extent prevented by
their compression between the mucous and muscular coats of the
bladder, where they run for more than half an inch before opening
at the posterior angle of the trigone. But it has been shown that
a certain amount of back flow can take place. Small bodies like
diatoms suspended in water and pigments dissolved in it have been
found in. the pelvis of the kidney, the renal tubules, and even the
circulation after being injected into the bladder.
The pressure in the bladder of a man may be made as high as
10 cm. of mercury during the act of micturition; about half this
amount is due to the contraction of the vesical walls alone, the
rest to the contraction of the abdominal muscles. A pressure of
16 to 26 mm. of mercury is required to open the sphincter of a
rabbit's bladder in life.
Although the whole performance seems to us to be completely
voluntary, there are facts which show that it is at bottom a reflex
EXPULSION OF THE URINE 511
series of co-ordinated movements, that can be started by impulses
passing to a centre in the spinal cord from above or from below —
from the brain or from the bladder. In dogs, with the spinal cord
divided at the upper level of the lumbar region, micturition takes
place regularly when the bladder is full, and can be excited by such
slight stimuli as sponging of the skin around the anus (Goltz).
Here, of course, the act is entirely reflex; and the centre is situated
at the level of the fifth lumbar nerves. The efferent nerves of the
bladder, like those of the rectum, come partly from the cord directly
through the sacral nerves, and partly through the lumbar sympa-
thetic chain (second to sixth ganglia). The sacral fibres are con-
nected with nerve cells in the hypogastric plexus, and the sympa-
thetic, partly at least, in the inferior mesenteric ganglia. This
anatomical coincidence acquires interest in view of the striking
physiological similarity between the processes of micturition and
defaecation, a similarity which is emphasized by the fact that the
latter is almost invariably accompanied by the former. An im-
portant difference, however, is that the will can far more readily
set in motion the machinery of micturition than that of defaecation ;
a man can generally empty his bladder when he likes, but he cannot
empty his bowels when he likes.
Sometimes in disease, and especially in disease of the spinal cord,
the mechanism of micturition breaks down; the bladder is no
longer emptied; it remains distended with urine, which dribbles
away through the urethra as fast as it escapes from the ureters.
To this condition the term incontinence of urine is properly
applied.
Reflex emptying of the bladder, without an act of will or during
unconsciousness, is not true incontinence. The involuntary mic-
turition of children during sleep, for example, is a perfectly normal
reflex act, although more easily excited and less easily controlled
than in adults. Section either of both nervi erigentes, or of both
hypogastrics, is never followed by more than quite temporary dis-
turbance of function of the bladder in dogs, both male and female.
In a few days the urine is normally passed. In bitches the same
is true when both pairs of nerves are divided. But in male dogs
true incontinence of urine follows section of the four nerves, as well
as intense tenesmus due to paralysis of the lower part of the large
intestine.
SECTION IV. — EXCRETION BY THE SKIN.
Besides permitting of the trifling gaseous interchange already
referred to (p. 299), the skin plays an important part in the elimina-
tion of water by the sweat-glands.
Sweat is a clear colourless liquid of low specific gravity (1003 to
1006), consisting chiefly of water with small quantities of salts,
514 EXCRETION
neutral fats, volatile fatty acids, and the merest traces of proteins
and urea. It is acid to litmus except in profuse sweating, when it
may become neutral or even alkaline. It is secreted by simple
gland-tubes, which form coils lined with a single layer of columnar
epithelium, in the subcutaneous tissue, with long ducts running up
to the surface through the true skin and epidermis. Unless col-
lected from the parts of the skin on which there, are no hairs, such
as the palm, it is apt to be mixed with sebum, a secretion formed
by the breaking down of the cells of the sebaceous glands, which
open into the hair follicles, and consisting chiefly of glycerin and
cholesterin fats, soaps, and salts. Sebum is probably of consider-
able importance for maintaining the normal condition of the hair
and skin.
Although it is only occasionally that sweat collects in visible
amount on the1 skin, water is always being given off in the form of
vapour. This invisible perspiration leaves behind it on the skin,
or in the glands, the whole of the non-volatile constituents, which
may be to some extent reabsorbed ; and since even the visible per-
spiration is in large part evaporated from the very mouths of the
glands in which it is formed, the sweat can hardly be considered a
vehicle of solid excretion, even to the small extent indicated by its
chemical composition.
The total quantity of water excreted by the skin, and the relative
proportions of visible and invisible perspiration, vary greatly. A
dry and warm atmosphere increases, and a moist and cold atmo-
sphere diminishes the total, and, within limits, the invisible per-
spiration. Visible sweat — given the condition of rapid heat-produc-
tion in the body as in muscular labour — is more readily deposited
on freely exposed surfaces when the air is moist than when it is dry.
The air in contact with surfaces covered by clothing is never far
from being saturated with watery vapour. Here, accordingly, a
comparatively slight increase in the activity of the sweat-glands
suffices to produce more water than can be at once evaporated;
and the excess appears as sweat on the skin, to be absorbed by
the clothing without evaporation, or to be evaporated slowly, as
the pressure of the aqueous vapour gradually diminishes in con-
sequence of diffusion. The power of imbibition (p. 426) of water
by the various layers of the skin diminishes as we pass outwards,
and the cells of the epidermis are characterized by the rapidity with
which they return from a condition of excessive imbibition to their
normal state. This constitutes a protective mechanism against
excessive loss of water. When the skin is thoroughly moistened, its
degree of imbibition is three times the normal.
The quantity of sweat given off by a man in twenty-four hours
varies so much that it would not be profitable to quote here the
numerical results obtained under different conditions of tempera-
EXCRETION By THE SKIN 513
ture and humidity of the air (but see p. 691). It is enough to say
that the excretion of water from the skin is of the same order of
magnitude as that from the kidneys: a man loses upon the whole
as much water in'sweat as in urine. But it is to be carefully noted
that these two channels of outflow are complementary to each
other; when the loss of water by the skin is increased, the loss by
the kidneys is diminished, and vice versa.
The Influence of Nerves on the Secretion of Sweat. — The sweat-
glands are governed directly by the nervous system; and though
an actively perspiring skin is, in health, a flushed skin, the vascular
dilatation is a condition, and not the chief cause of the secretion.
Stimulation of the peripheral end of the sciatic nerve causes a
copious secretion of sweat on the pad and toes of the corresponding
foot of a young cat, and this although the vessels are generally
constricted by excitation of the vasomotor nerves. Not only so,
but when the circulation in the foot is entirely cut off by compres-
sion of the crural artery or by amputation of the limb, stimulation
of the sciatic still calls forth some secretion. As in the case of the
salivary glands, injection of atropine abolishes the secretory power
of the sciatic, while leaving its vaso- motor influence untouched; and
pilocarpine increases the flow of sweat by direct stimulation of the
endings of the secretory nerves in the glands.
That the sweating caused by a high external temperature is
normally brought about by nervous influence, and not by direct
action on the secreting cells, is shown by the following experiments.
One sciatic nerve is divided in a cat, and the animal put into a hot-
air chamber. No sweat appears on the foot whose nerve has been
cut, but the other feet are bathed in perspiration. Similarly, a
venous condition of the blood (in asphyxia) causes sweating in the
feet whose nerves have not been divided, but none in the other
foot ; and stimulation of the central end of the cut sciatic has the
same effect. All this points to the existence of a reflex mechanism ;
and it is certain that asphyxia acts by direct stimulation of the
centre or centres. The vaso-motor centre is at the same time
stimulated, and the bloodvessels constricted, as in the cold sweat
of the death agony. Fear may also cause a cold sweat, impulses
passing from the cerebral cortex to the vaso-motor and sweat
centres.
It is probable that a general sweat - centre exists in the medulla
oblongata, but its position has not been exactly determined nor even
its existence definitely proved. On the other hand, it is known that
in the cat there are at least two spinal centres, one for the fore-limbs
in the lower part of the cervical cord, and another for the hind-limbs
where the dorsal portion of the cord passes into the lumbar. That this
latter centre does not exist or is comparatively inactive in man is
indicated by the following case : A man fell from a window and fractured
his backbone at the fifth dorsal vertebra. The lower half of the body
was paralyzed for a time, but recovered. Ultimately, however, the
33
5I4 EXCRETION
paralysis returned ; and shortly before his death (twenty-one years after
the accident) it was noticed that a copious perspiration broke out
several times on the upper part of the body, while the lower portion
remained perfectly dry. If there is any functional spinal centre in man,
it appears to lie above the fifth spinal segment. For it was seen in a
professional diver who fractured his neck at that level, and lived three
months after the accident, that sweat frequently appeared on parts of
the body above the lesion, but never below. At the autopsy the whole
thickness of the cord, except perhaps a small portion of the anterior
columns, was found destroyed. Of course, it may be that in man the
spinal centres, although normally active, lose their function for a long
time after such severe injuries to the cord, owing to the condition known
as shock.
The secretory fibres for the fore-limbs (in the cat) leave the cord in
the anterior roots of the fourth to ninth thoracic nerves. They pass by
white ranii communicantes to the sympathetic chain, in which they
reach the ganglion stellatum, where they are all connected with nerve-
cells. Then, as non-medullated fibres, they gain the brachial plexus
by the grey rami, and run in the median and ulnar to the pads of the
feet. The fibres for the hind-limbs leave the cord in the anterior roots
of the twelfth thoracic to the third or fourth lumbar nerves ; pass by the
white rami to the sympathetic ganglia, in which they form connections
with ganglion cells ; then, as non-medullated fibres, run along the grey
rami, and are distributed to the foot in the sciatic.
The evidence of the direct secretory action of nerves on the sweat-
glands is singularly striking and complete, in contrast to what we
know of the kidney. In the latter, blood-flow is the important
factor; increased blood-flow entails increased secretion. In the
former, the nervous impulse to secretion is the spring which sets
the machinery in motion; vascular dilatation aids secretion, but
does not generally cause it. It would, however, be easy to lay too
much stress on this distinction, for in the horse the mere dilatation
of the bloodvessels of the head after section of the cervical sympa-
thetic has been found to be accompanied by increased secretion of
sweat, and urinary secretion can certainly be affected by the direct
action of various substances on the secretory mechanism, indepen-
dently of vascular changes. But the broad difference stands out
clearly enough, and the reason of it lies in the essentially different
purpose of the two secretions. The water of the urine is in the
main a vehicle for the removal of its solids; the solids of the sweat
are accidental impurities, so to speak, in the water. The kidney
eliminates substances which it is vital to the organism to get rid
of; the sweat-glands pour out water, not because it is in itself
hurtful, not because it cannot pass out by other channels, but
because the evaporation of water is one of the most important
means by which the temperature of the body is controlled. In
short, urine is a true excretion, sweat a heat-regulating secretion.
No hurtful effects are produced when elimination by the skin is
entirely prevented by varnishing it, provided that the increased
loss of heat is compensated. A rabbit with a varnished skin dies
PRACTICAL EXERCISES 5!5
of cold, as a rabbit with a closely-clipped or shaven skin does;
suppression of the secretory function of the skin has nothing to do
with death in the first case any more than in the second (p. 299).
PRACTICAL EXERCISES ON CHAPTER IX.
Urine.
For most of the experiments human urine is employed — in the
quantitative work the mixed urine of the twenty-four hours . Urine may
also be obtained from animals. In rabbits pressure on the abdomen
will usually empty the bladder. Dogs may be taught to micturate at
a set time or place, or kept in a cage arranged for the collection of urine.
Or a catheter may be used (p. 716).
i. Specific Gravity. — Pour the urine into a glass cylinder, and remove
froth, if necessary, with filter-paper. Place a urinometer (Fig. 193)
in the urine, and see that it does not come in contact
with the side of the vessel. Read off on the graduated
10 stem the division which corresponds with the bottom
0 of the meniscus. This gives the specific gravity.
,„ 2. Reaction. — (a) Test with litmus-paper. Generally
the litmus is reddened, but occasionally in health the
urine first passed in the morning is alkaline. Some-
times urine has an amphicroic reaction — i.e., affects
both red and blue litmus-paper. This is the case when
there is such a relation between the bases and acids
that both acid and ' neutral ' (dibasic) phosphates are
present in certain proportions. The acid phosphate
reddens blue litmus, and the ' neutral ' phosphate
turns red litmus blue.
(b) TitrataUe Acidity. — To 25 c.c. of urine add 15
to 20 grammes of powdered potassium oxalate, and
one or two drops of a i per cent, solution of phenol-
phthalein. Shake the ^mixture rapidly for a minute
Fig. 193. — Urin- or two, and then titrate with decinormal sodium hy-
ometer. droxide at once (while still cold from the solution of the
oxalate) till a faint pink colour remains permanent on
shaking. The potassium oxalate is added to counteract the tendency
of the calcium present in urine to form basic phosphates, which would
be precipitated, and the acidity of the urine thus increased (Folin).
3. Chlorides — (a) Qualitative Test. — Add a drop of nitric acid and a
drop or two of silver nitrate solution. The nitric acid is added to
prevent precipitation of silver phosphate. A white precipitate soluble
in ammonia shows the presence of chlorides. The precipitate appears
to be incompletely soluble in ammonia, since the ammonia brings down
a small precipitate of earthy phosphates.
(b) Quantitative Estimation. — The quantitative estimation of the
chlorine in urine without previous evaporation and incineration is best
made by one of the modifications of Volhard's method. It depends upon
the complete precipitation of the chlorine combined with the alkaline
metals, and also of sulphocyaiiic acid, by silver from a solution con-
taining nitric acid in excess ; and avoids the error introduced into simpler
methods, like Mohr's, by the union of some of the silver with other
substances than chlorine. A given quantity of a standard solution of
5i6 EXCRETION
silver nitrate (more than sufficient to combine with all the chlorine) is
added to a given volume of urine. The excess of silver is now estimated
by means of a standard solution of ammonium sulphocyanide, which
precipitates the silver as insoluble silver sulphocyanide. A fairly strong
solution of the double sulphate of iron and ammonium (known as iron-
ammonia-alum) is taken as the indicator, since a ferric salt does not
give the usual red colour with a sulphocyanide so long as any silver in the
solution is uncombined with sulphocyanic acid. The iron-ammonia-
alum forms the red salt, ferric sulphocyanide, when any excess of
ammonium sulphocyanide is present, but it does not react with silver
sulphocyanide .
The standard solution of silver nitrate can be made by dissolving
29-063 grammes of pure fused silver nitrate in distilled water and making
up the volume of the solution accurately to I litre. The solution should
be kept in the dark. One c.c. of this solution corresponds to
o-oi gramme NaCl or 0-00607 gramme Cl.
The standard solution of ammonium sulphocyanide is prepared as
follows: Dissolve 13 grammes of pure ammonium sulphocyanide
(NH4CNS) in a litre of distilled water. Measure with a pipette into
a beaker 20 c.c. of the standard silver nitrate solution, and add 5 c.c.
of the iron alum solution and 4 c.c. of pure nitric acid (specific gravity
1-2). Fill a burette with the sulphocyanide solution, and run it into
the silver nitrate solution until a faint permanent red tinge is obtained.
Note the number of c.c. of the sulphocyanide solution required, and
then dilute the solution till 2 c.c. of the sulphocyanide solution corre-
spond exactly to i c.c. of the silver solution, so as just to allow of the
end reaction with the iron solution being seen, and no more.
To carry out the method, put 10 c.c. of urine, which must be free
from albumin, in a stoppered flask, with a mark corresponding to ipo c.c.
or a graduated cylinder. Add 50 c.c. of water, 4 c.c. of pure nitric acid
(specific gravity 1-2), and 15 c.c. of the standard silver solution; shake
well, fill with water to the mark, and again shake. After the precipitate
has settled, filter it off. Take 50 c.c. of the nitrate, add 5 c.c. of the
solution of iron-ammonia-alum, and run in from a burette the standard
solution of ammonium sulphocyanide until a weak but permanent red
coloration appears.
Suppose x c.c. of the sulphocyanide solution are required, then the
chlorine in 10 c.c. of urine evidently corresponds to (15 — x), o'oi gramme
NaCl
4. Phosphates — (i) Qualitative Tests. — (a) Render the urine alkaline
with ammonia. A precipitate of earthy phosphates (calcium and mag-
nesium phosphates) falls down. Filter. The filtrate contains the
alkaline phosphates. To the filtrate add magnesia mixture.* The
alkaline phosphates (sodium, potassium, or ammonium phosphates)
are precipitated as ammonio-magnesic or triple phosphate, (b) Add to
urine half its volume of nitric acid and a little molybdate of ammonium,
and heat. A yellow precipitate of ammonium phospho-molybdate
shows that phosphates are present. This test is given both by alkaline
and earthy phosphates.
(2) Quantitative Estimation. — The quantitative estimation of phos-
phoric acid in urine is best done volumetrically, by titration with a
standard solution of uranium nitrate, using ferrocyanide of potassium
as the indicator. Uranium nitrate gives with phosphates, in a solution
containing free acetic acid, a precipitate with a constant proportion of
* Magnesium chloride no grammes, ammonium chloride 140 grammes,
ammonia (specific gravity 0-91) 250 c.c., and water 1,750 c.c.
PRACTICAL EXERCISES 517
phosphoric acid. As soon as there is more uranium in the solution than
is required to combine with all the phosphoric acid, a brown colour is
given with potassium ferrocyanide, due to the formation of uranium
ferrocyanide. In carrying out the method, 5 c.c. of a mixture of acetic
acid and sodium acetate (there are 10 grammes of sodium acetate and
10 grammes of glacial acetic acid in 100 c.c. of the mixture) are added
to 50 c.c. of urine, which is then heated in a beaker on the water-bath
almost to boiling. The standard uranium solution (which contains
35-5 grammes of uranium nitrate in the litre, and I c.c. of which corre-
sponds to 0-005 gramme PaO5) is now run in from a burette, until a drop
of the urine gives, with a drop of potassium ferrocyanide solution, on a
porcelain slab, a brown colour. Uranium acetate may be used instead
of uranium nitrate, but the latter keeps best. When uranium acetate
is employed it is not necessary to add the sodium acetate mixture.
5. Sulphates — (i) Qualitative Test. — Add to urine a drop of hydro-
chloric acid and then a few drops of barium chloride. A white pre-
cipitate comes down, showing that inorganic sulphates are present.
The hydrochloric acid prevents precipitation of the phosphates.
(2) Quantitative Estimation of the Sulphates (Inorganic and Ethereal).
— Add to 50 c.c. of albumin-free urine in a 2OO-C.C. Erlenmeyer flask
5 c.c. of a 4 per cent, potassium chlorate solution and 5 c.c. of strong
hydrochloric acid, and boil the mixture to break up the ethereal sul-
phates. In five to ten minutes it becomes perfectly colourless. While
it continues to boil, 25 c.c. of a 10 per cent, solution of barium chloride
are added by drops, at such a rate that it takes about five minutes to
add this quantity. The flask is now put on the water-bath for one-half
to one hour, till the precipitate has settled. Then filter through an
ash-free filter. Wash the precipitate on the filter for half an hour with
hot water. During the first twenty minutes of the washing, at intervals
of a few minutes, substitute hot 5 per cent, ammonium chloride solution
for the water. At the end of the half -hour's washing, as soon as the
water has run through the filter, fold up the latter and press it gently
between dry filter-papers to remove a portion of the water. Then place
the filter in a weighed porcelain crucible. Pour into the crucible 3 or 4
c.c. of alcohol, and ignite it, to dry and partially burn the filter-paper.
Then incinerate till all the carbon is burned off> cool, and weigh. From
the weight of the barium sulphate, the sulphuric acid in 50 c.c. of urine
is easily calculated (SO4 in I gramme of barium sulphate, 0-41187
gramme) (Folin).
(3) Quantitative Estimation of the Sulphuric Acid united with Aromatic
Bodies (Aromatic or Ethereal Sulphates). — Put 200 c.c. of the same urine
as used in (2) into a beaker. Add 100 c.c. of 10 per cent, barium
chloride solution in the cold. Let stand for twenty-four hours. Then
decant off the clear supernatant liquid, and filter it. Measure 150 c.c.
of the clear filtrate, corresponding to 100 c.c. of the urine, into a 400-0. c.
Erlenmeyer flask. Add 10 or 15 c.c. of concentrated hydrochloric acid
and 10 to 15 c.c. of 4 per cent, potassium chlorate. Heat the mixture
to boiling, and proceed as in (2). From the weight of the barium sul-
phate, the ethereal sulphuric acid in 100 c.c. of urine can be calculated.
Deducting this from the quantity per 100 c.c. of urine obtained in (2),
we get the amount of inorganic sulphuric acid per 100 «.c. (Folin).
6. Indoxyl (contained in the urine as indican, the potassium salt of
indoxyl-sulphuric acid) can be oxidized into indigo, and so detected
and estimated.
A qualitative test is the following: Ten c.c. of horse's urine is mixed
with 10 c.c. of Obermayer's reagent (pure concentrated hydrochloric
acid containing 2 to 4 parts of ferric chloride in 1,000), and shaken well
51 8 EXCRETION
for a minute or two ; a bluish colour appears if, as is generally the case,
indoxyl is present, indigo (C16H10N2O2) being formed by the oxidizing
action of the ferric chloride on the indoxyl, the compound of which
with sulphuric acid has been broken up by the hydrochloric acid. The
urine must be free from albumin. In performing the test in human
urine, which contains a smaller quantity of the indigo-forming sub-
stance, the fault blue liquid should be shaken up with a few drops of
chloroform. The latter takes up the colour, which is thus rendered
more evident. If there is difficulty in obtaining the reaction, the urine
may first be decolorized by precipitating it with acetate of lead,
avoiding excess. The precipitate is filtered off, and the test then
applied to the clear filtrate. The skatoxyl of urine can also be oxidized
to indigo, but it is present in far smaller amount. The average quantity
of indigo obtained from a litre of horse's urine is about 150 milligrammes ;
from a litre of human urine, not a twentieth of that amount.
For comparative quantitative determinations the method of Folin
may be used. One-hundredth of the twenty-four hours' urine is taken.
In this the indigo is developed by the addition of an equal volume of
Obermayer's reagent (p. 5l«7), and the indigo-blue dissolved by means
of 5 c.c. of chloroform. The chloroform solution is then compared
colorimetrically with Fehling's solution. This can be done by putting
the indigo solution and 5 c.c. of the Fehling's solution respectively into
small test-tubes of equal calibre, and comparing the depth of tint.
If the Fehling's solution is stronger than the indigo solution, run water
into the former from a pipette, graduated in tenths of a c.c., shaking
up after each addition, till equality of tint has been reached. If the
indigo solution has a stronger blue colour than the Fehling's solution,
dilute a measured amount of it first of all with such a quantity of
chloroform (say an equal volume) as will make its tint distinctly weaker
than that of the Fehling's solution. Then dilute the Fehling's solution
with water, as before, till the tint is the same. From the amount of
dilution the quantity of indigo can be expressed in arbitrary units,
taking Fehling's solution as 100. Thus, if I c.c. of water must be
added to the 5 c.c. of Fehling's solution, the indican can be expressed
as = 5— = 83. The comparison can be made more accurately by
5
a colorimeter, if one is available. To determine the absolute amount
of indigo obtained, comparison must be made with a standard solution
of indigo.
7. Urea — (i) Decomposition of Urea. — Heated dry in a test-tube, it
gives off ammonia. The residue contains biuret, which, when dissolved
in water, gives a rose colour with a trace of cupric sulphate and excess
ot sodium hydroxide (or of the hydroxides of certain other metals of
the alkalies and alkaline earths (p. 8). Some proteins — peptones and
albumoses — in the presence of the same reagents, give a similar colour,
the so-called biuret reaction.
(2) Quantitative Estimation — Marshall's Urease Method. (According
to Van Slyke). — One-half c.c. of urine is measured into the bottom of
tube A (Fig. 194). Five c.c. exactly of a 0-6 per cent, solution of
KH2PO4 is then run in from a burette, and I c.c. exactly of a 10 per
cent, watery solution of the dry urease powder. The phosphate is
added as a ' buffer ' to maintain the enzyme action near its maximum
rate, by preventing the development of alkalinity as the production of
ammonium carbonate goes on. The solutions in the tube are well
PRACTICAL EXERCISES 519
mixed, 2 drops of caprylic alcohol are added to prevent foaming during
the subsequent aeration (by Folin's method, p. 521), and the stopper
bearing the aerating tubes is put into place. Let stand twenty minutes
at room temperature of 15°, or fifteen minutes at 20° C. or above, for
complete decomposition of urea. This time must not be shortened
unless more enzyme is used, but no harm is done if it is longer. Mean-
while measure into tube B 25 c.c. |^ hydrochloric or sulphuric acid,
i drop of i per cent, sodium alizarine sulphonate indicator, and
i drop caprylic alcohol, and connect the
tubes as shown in Fig. 194. After the
twenty minutes for decomposition of urea
has elapsed, the air current is passed for
half a minute to sweep into B, a small
amount of ammonia which has escaped
into the air space of A during the decom-
position. Then A is opened, and 4 to
5 grammes potassium carbonate added to
liberate the ammonia from the ammonium
carbonate formed. Now let the air cur-
rent pass gently through the tubes for
the first minute and then rapidly until
all the ammonia has been brought into
the acid in B. The time necessary for
this will depend upon the speed of the
air current (varying from five minutes to
half an hour, according to the efficiency
of the pump or vacuum by which the air
is moved) and should be determined once
for all. The excess- acid in B is now
titrated with ^ sodium hydroxide. The
Fig. 194. — Apparatus for deter-
mining Urea Content by means
of Urease. (After Van Slyke.)
weight of nitrogen contained in the urea of 100 c.c. of urine is
(25 - x) x 0-056, where x is the number of c.c. of the sodium hydroxide
solution necessary to neutralize the acid. Included in the urea
nitrogen is the nitrogen of any ammonia originally present in the
urine. This can be determined separately, if desired, by putting
5 c.c. of urine into A without urease, adding the carbonate at once,
and then aerating through the acid in B. The acid neutralized in
this case is multiplied by 0-0056 to give the ammonia nitrogen in 100 c.c.
of urine, and this being deducted from the previous result, the net urea
nitrogen is obtained.
The method as above described is adapted for urine containing not
more than 3 per cent, urea, which is about the maximum found in human
urine. Cat's or dog's urine should first be diluted to reduce the urea
below 3 per cent.
Clinical Urease Method by Direct Titration of Urine. — Two 5 c.c.
portions of urine are put into flasks a and b of 200 to 300 c.c. capacity,
and diluted with distilled water to about 100 to 125 c.c. One c.c. of
10 per cent, urease is added to flask a, and a few drops of toluene to
each. The flasks are allowed to remain, well stoppered, at room tempera-
ture over night, then titrated to a distinct pink colour with ^ hydro-
chloric acid, using methyl orange as indicator. From the amount of
hydrochloric acid needed for a is deducted the amount needed for b;
and also the amount previously determined to be necessary to neutra-
lize the alkalinity of the enzyme solution. The remaining number of
c.c. multiplied by 0-6 gives the urea in gvammes per litre of urine, since
520
EXCRETION
i c.c. of N hydrochloric acid is equivalent to 3 milligrammes of urea.
Instead of the dried urease preparation, an extract of finely powdered
soy beans can be made by mixing 25 grammes of the powder with
250 c.c. of distilled water, and allowing it to stand with occasional
shaking for an hour. Twenty-five c.c. of ^ hydrochloric acid are then
added, and the mixture allowed to remain a few minutes longer (best
at about 35° C.). The mixture is filtered, treated with a few drops of
toluene, and preserved for use in a stoppered bottle. It must be made
up fresh after a few days as it does
not keep long. The solution is alka-
line to methyl orange, and 2 c.c. (the
quantity used in the above clinical
determination of urea) generally re-
quires about o«3 c.c. of N hydro-
chloric acid for neutralization.
A less exact method which is very
rapid, and is therefore much used in
clinical determinations, is the Hypo-
bromite Method. The urea is split up
by sodium hypobromite (p. 480), and
the carbon dioxide being absorbed by
the excess of sodium hydroxide used
in preparing the hypobromite, the
nitrogen is collected over water in an
inverted burette. It is easy to calcu-
late the weight of urea corresponding
to a given volume of nitrogen measured
at a given temperature and pressure.
The nitrogen of urea is f §, or fa of the
whole molecular weight. Now, i c.c.
of N weighs, at 760 millimetres of
mercury and o° C., 0-00125 gramme.
Therefore, i c.c. of N corresponds to
0-00125x^=0-00268 gramme urea.
Suppose, now, that i c.c. of urine was
found to yield 10 c.c. of N measured
at 17° C. and 750 millimetres barome-
tric pressure. Since a gas expands
volume at o° for every
Fig. 195. — Hypobromite Method
of estimating Urea. A, glass
thimble; B, bottle, through the
rubber cork of which pass two
short glass tubes, one connected ^_ w iw .„...„„, „,„ v iw C¥C1>
by the rubber tube C with a degree above o°, we must correct the
burette D, and the other armed apparent volume of nitrogen by multi-
plying by f |§. Since the volume of a
gas is inversely proportional to the
pressure, we must further multiply
by Ijft. Thus we get 10 x \ J$ x fflf -
**!££• =9*29 c.c. as the volume of the
"nitrogen reduced to o° C. and 760 milli-
metres of mercury. Multiplying this by 0-00268, we get 0-0249 gramme
urea for i c.c. urine, which for a daily yield of 1,200 c.c. would corre-
spond to 29-88 grammes urea.
As a matter of fact, however, it has been found that there is always
a deficiency of nitrogen — that is, a given quantity of urea yields less
than the estimated amount of gas. A gramme of urea in urine, instead
of giving off 373 c.c. of nitrogen, gives only 354 c.c. at o° C. and 760
millimetres pressure. We must therefore take i c.c. of N as correspond-
with a short piece of rubber tube
F. F is provided with a pinch-
cock. The burette is supported
on a stand, and immersed in
water contained in the glass
cylinder E.
PRACTICAL EXERCISES 521
ing to 0-00282 gramme, instead of 0-00268 gramme urea. But it is
affectation to make this correction if, as is seldom done in hospitals, the
temperature is not taken into account.
A convenient apparatus is shown in Fig. 195. In B place 10 c.c.
of a solution made by adding bromine to ten times its volume of 40 per
cent, sodium hydroxide solution. Mix 5 c.c. of urine with 5 c.c. of
water. Put 5 c.c. of the mixture into the thimble A, which is then set
in the small bottle B. The cork is now carefully fixed in B, and the
tube F being open, the level of the water in the burette is read off.
The pinchcock having been closed, the bottle B is now tilted so that
the urine in the thimble is gradually mixed with the hypobromite solu-
tion, and the nitrogen given off is added to the air in the burette and
its connections. The level of the water in the burette is therefore
depressed. When gas ceases to be given off, and a short time has been
allowed for the whole to cool, the tube is raised till the level of the
water is once more the same inside and out. The. level is again read
off ; the difference of the two readings gives the volume of nitrogen at
the temperature of the air and the barometric pressure. In order that
the temperature of the water may be the same as that of the air, the
cylinder should be filled a considerable time before the observations
are begun.
8. Estimation of the Ammonia in Urine (Folin's Method). — Ammonia
is liberated by addition of a weak alkali (sodium carbonate). Then
the ammonia is driven out at ordinary temperature by a strong current
of air and taken up in decinormal acid, which is then titrated with
decinormal alkali.
The apparatus employed consists of — (i) A cylinder of about 45 cm.
diameter, with a rubber stopper through which pass two glass tubes.
One of the tubes goes nearly to the bottom of the cylinder, and the
other end is connected, through a U-tube filled with cotton, with a tube
containing sulphuric acid. The second tube is cut off short below the
rubber cork, and its other end is connected, through a U-tube con-
taining cotton, with a sulphuric acid tube (or with two in series) . (2) A
water-pump to draw or force air through the apparatus (600 to 700
litres in an hour) .
Put into the first sulphuric acid tube 25 c.c., into the second 10 c.c.
decinormal acid and some water; into the cylinder 25 c.c. of filtered
urine, 8 to 10 grammes sodium chloride, 5 to 10 c.c. of petroleum or
toluol to prevent foaming, and last of all i gramme dried sodium
carbonate. At once close the cylinder and allow a strong stream of air
to pass through the apparatus. At a temperature of 20° to 25° (room
temperature), and using 600 to 700 litres of air an hour, all the ammonia
is in the sulphuric acid in one to one and a half hours. The contents
of the sulphuric acid tubes are put into a beaker and titrated with
decinormal alkali, using lacmoid (litmoid) or rosolic acid as indicator.
Deduct the number of c.c. of alkali used from the number of c.c. of the
decinormal acid originally taken, and multiply the remainder by 1-7034
to get the quantity of ammonia in milligrammes. The method can be
employed also for albuminous urine.
9. Estimation of the Total Nitrogen. — It is sometimes more important
to determine the total nitrogen of the urine than the urea alone. This
is conveniently done by Kjeldahl's method (or some modification of
it), which can also be applied to the estimation of the nitrogen in the
faeces, or in any of the solids or liquids of the body. It depends on the
oxidation of the nitrogenous matter (or, rather, in the case of urine,
mainly its hydrolysis) in such a way that the nitrogen is all represented
522 EXCRETION
as ammonia. The ammonia is then distilled over, collected and esti-
mated, and from its amount the nitrogen is easily calculated. In urine
the method can be carried out by adding to a measured quantity of it
(say 5 c.c.) four times its volume of strong sulphuric acid, and boiling
in a long-necked flask (capacity 200 c.c.), after the addition of a globule
of mercury (about o-i c.c.), which hastens oxidation and obviates
bumping. A part of the mercuric sulphate formed remains in solution ;
the rest forms a crystalline deposit. The heating should continue for
half an hour, or until the liquid is decolourized. It should be kept
gently boiling. This completes the process of oxidation ; and the next
step is to liberate the ammonia from the substances with which it is
united in the solution, and to distil it over. Dilute the liquid with
water, after cooling, up to about 150 c.c., and pour into a larger long-
necked flask. Add enough of a solution of sodium hydroxide (specific
gravity about 1-25) to render the liquid alkaline, avoiding excess, as
this favours bumping. The proper quantity can be found by deter-
mining beforehand how much of the alkali is needed to neutralize the
acid used for oxidation, and a little more than this amount should be
added. Twenty c.c. of strong sulphuric acid needs about 75 c.c. of
40 per cent, sodium hydroxide to neutralize it. Bumping may further
be prevented by the addition of a little granulated zinc. Shake the
flask two or three times. Add also about 12 c.c. of a concentrated
solution of potassium sulphide (i part to i£ parts water), which favours
the setting free of the ammonia from the amino-compounds of mercury
that have been formed during oxidation . Commercial ' liver of sulphur '
will do quite well. Immediately connect the distilling-flask with a
worm or Liebig's condenser, and distil the ammonia over into 50 c.c.
of standard (decinormal) sulphuric acid (see footnote, p. 473) con-
tained in a flask into which a glass tube connected with the lower end
of the worm dips. Heat the distilling-flask at first gently, then strongly,
and boil for three-quarters of an hour, or until about two-thirds of the
liquid has passed over. Then lift the tube out of the standard acid, and
continue the distillation for two or thiee minutes longer. The ammonia
is now all united with the standard acid, a certain amount of which is
left over. By determining this amount we arrive at the quantity com-
bined with ammonia, and therefore at the quantity of ammonia. Fill
a burette with a decinormal solution of potassium or sodium hydroxide.
Add a little methyl-orange solution to the standard sulphuric acid, to
serve as indicator. Then run in the potassium or sodium hydroxide
till the pink tinge gives place to a permanent but just recognizable
yellow. Let x be the number of c.c. run in. Since i c.c. of any deci-
normal solution is equivalent to i c.c. of any other, x represents also the
number of c.c. of the standard sulphuric acid left uncombined with
ammonia; and 50 — x, the quantity combined with ammonia. Then,
i c.c. of decinormal sodium or potassium hydroxide being equivalent
to i c.c. of decinormal ammonium hydroxide, and i c.c. of decinormal
ammonium hydroxide containing 0-0014 gramme nitrogen, we get
(50- x) x 0-0014 as the quantity of nitrogen in 5 c.c. of urine.
Instead of mercury, potassium sulphate and copper sulphate may be
added to the sulphuric acid in order to aid the decomposition in the
first stage of the estimation. About 3 grammes of potassium sulphate
and i gramme of copper sulphate are added to £ c.c. of urine, and then
5 c.c. of sulphuric acid. The liquid is gently boiled for an hour, or until
it is quite clear. The neutralization and distillation are conducted as
before, the proper quantity of sodium hydroxide being determined in
advance. No potassium sulphide is added, but a small quantity of
PRACTICAL EXERCISES 523
talc may be put in to prevent bumping. Instead of methyl orange,
' alizarin red,' which is bright red in the presence of the slightest trace
of alkali, may be used.
10. Uric Acid — (i) Qualitative Test for Uric Acid — Murexide Test. —
A small quantity of uric acid or one of its salts is heated with a little
dilute nitric acid. The colour of the residue left by evaporation
becomes yellow, and then red, and on the addition of ammonia changes
to deep purple-red. Potassium or sodium hydroxide changes the
yellow to violet. In the reaction alloxantin is formed by oxidation of
the uric acid. When ammonia acts on alloxantin it is changed into
purpuric acid, and this into its ammonium purpurate, the purple-red
substance called murexide. Thus:
C8H6N408+ NH3 =C8H5N60?+ 2HaO.
Alloxantin. Purpuric Acid.
The reaction is also given by theobromine (dimethylxanthin), an alkaloid
in cocoa, and theine or caffeine (trimethylxanthin), an alkaloid in tea
and coffee, which are also purin derivatives (p. 48 1')-
(2) Quantitative Estimation — • Folin's Modification of Hopkins' s
Method. — The chief reagent is a solution of 500 grammes ammonium
sulphate, 5 grammes uranium acetate, and 60 c.c. 10 per cent, acetic
acid, in 650 c.c. of water.
One hundred and fifty c.c. of urine is measured into a tall, narrow
beaker or a cylinder, and 37^ c.c. of the reagent added. If enough
urine is available, 200 c.c. of urine and 50 c.c. of reagent are to be used.
Allow the mixture to stand without stirring for about half an hour.
The uranium precipitate has then settled, and the clear supernatant
liquid is removed by siphoning or decantation. One hundred and
twenty-five c.c. of this liquid is measured into another beaker, 5 c.c.
of strong ammonia added, and the mixture set aside till next day. The
precipitate is then filtered off, and washed with 10 per cent, ammonium
sulphate solution until the filtrate is quite or nearly free from chlorides.
The filter is then removed from the funnel, opened, and the precipitate
rinsed back into the beaker. Enough water to make about 100 c.c. is
added, and the precipitate is then dissolved by means of 15 c.c. con-
centrated sulphuric acid, and at once titrated with ^6 (one -twentieth
normal) potassium permanganate solution (made by dissolving
1-581 grammes of the permanganate in a litre of water), each c.c. of
which corresponds to 3-75 milligrammes of uric acid. The very first
pink coloration, extending through the entire liquid on the addi-
tion of two drops of permanganate solution, marks the end point.
A correction of 3 milligrammes, owing to the solubility of ammonium
urate, is added to the result.
11. Creatinin. — Qualitatively, creatinin may be recognized in very
small amounts by Weyl's test. A few drops of a dilute solution of
sodium nitro-prusside are added to urine, and then dilute sodium
hydroxide drop by drop. A ruby-red colour appears, which soon turns
yellow. If the urine is now strongly acidified with acetic acid and
heated, it becomes first greenish and then blue. Enough acid must be
added to more than neutralize the alkali.
Another test which has been made the basis of a quantitative method
by Folin is Jaffe's test. A little urine (say 5 c.c.) is put in a test-tube,
and then a solution of picric acid in water. The mixture is rendered
alkaline by the addition of potassium or sodium hydroxide solution,
and a reddish colour is produced, which turns yellow on the addition of
52 4 EXCRETION
acid. A similar red colour is given by dextrose, but not unless the
solution is heated.
Quantitative Estimation of Creatinin by Folin's Method. — It depends
upon the comparison of the colour which* creatinin gives with picric
acid in an alkaline solution with that of a standard solution of potassium
bichromate. Ten c.c. of urine is measured into a 500 c.c. measuring-
flask; 15 c.c. of a saturated picric acid solution (containing about
12 grammes per litre) and 5 c.c. of a 10 per cent, solution of sodium
hydroxide are added. The mixture is allowed to stand for five minutes.
Then water is added up to the 500 c.c. mark, and the flask shaken to
mix uniformly. Samples of the liquid are then at once compared
colorimetrically with a half-normal solution of potassium bichromate
containing 24-55 grammes per litre. The colour of the urine does not
introduce a sensible error on account of the great dilution". For exact
work the comparison must be made with a good colorimeter. It has
been found experimentally that, when to milligrammes of creatinin
are present in 500 c.c. of a solution made as described, a layer of the
solution 8-1 millimetres in thickness has the same depth of tint as 8 milli-
metres of the bichromate solution. Suppose it takes 9 millimetres ol
the urine-picrate solution to equal 8 millimetres of the bichromate,
O. j
then the 10 c.c. of urine contains 10 x — =9-0 milligrammes of
creatinin.
12. Hippuric Acid. — From horse's or cow's urine hippuric acid is
prepared by evaporating to a small bulk, and adding strong hydrochloric
acid. The crystalline precipitate is washed with cold water, then
dissolved in hot water, and filtered hot. Hippuric acid separates out
from the filtrate in the cold in the form of long four-sided prisms with
pyramidal ends. Heated dry in a test-tube, the crystals melt, and
benzoic acid and oily drops of benzonitrile, a substance with a smell
like that of oil of bitter almonds, are formed.
ABNORMAL SUBSTANCES IN URINE.
13. Proteins — (i) Qualitative Tests. — (a) Boil and add a few drops
of nitric acid. A precipitate on boiling, increased or not affected by
the acid, shows the presence of coagnlable proteins (serum-albumin or
globulin). A precipitate of earthy phosphates sometimes forms on
boiling. It is distinguished from a precipitate of proteins by dissolving
on the addition of acid.
(b) Heller's Test. — Put some nitric acid in a test-tube. Pour care-
fully on to the surface of the acid a little urine. A white ring at the
junction of the liquids indicates the presence of albumin or globulin.
If much albumose is present, a white precipitate, which disappears on
heating, may be formed. When this test is performed with undiluted
urine, uric acid may be precipitated and cause a brown colour at the
junction. A similar ring may be found in the absence of proteins when
the test is made on the urine of a patient who has been taking copaiba.
In very concentrated urine a white ring of nitrate of urea may be
formed. A coloured ring is frequently seen, owing to the oxidation of
certain chromogens of urine.
(c) Filter some urine, and add to the filtrate its own volume of acetic
acid. A precipitate may indicate mucin or nucleo -albumin. If any is
formed, filter ft off, and add to the filtrate a few drops of potassium
ferrocyanide. A white precipitate shows the presence of proteins.
(d) Test for Globulin in Urine. — Serum-globulin probably never
PRACTICAL EXERCISES 525
occurs in urine apart from serum-albumin. It may be detected thus:
Make the urine alkaline with ammonia, let it stand for an hour, and
filter. Half saturate the filtrate with ammonium sulphate — i.e., add
to it an equal volume of a saturated solution of ammonium sulphate.
Serum-globulin is precipitated, serum-albumin is not.
(e) Test for Albumose in Urine (Albumosuria] . — Coagulable proteins
are removed by boiling the urine (acidulated if necessary), and filtering
off the precipitate if any. The filtrate is neutralized. If a further
precipitate falls down it is filtered off, the clear filtrate is heated in a
beaker placed in a boiling water-bath, and there saturated with crystals
of ammonium sulphate. A precipitate indicates that albumoses
(proteoses) are present. A slight precipitate might possibly be due to
the formation of ammonium urate. A further test may be performed
on the original urine if it is free from coagulable proteins, or on the
filtrate after their removal. Add a drop or two of pure nitric acid.
If albumoses are present, a precipitate is thrown down which disappears
on heating, and reappears on cooling the test-tube at the cold-water tap.
(2) Quantitative Estimation of Coagulable Proteins (Serum-Albumin
and Globulin) — (a) Gravimetric Method. — Heat 50 to 100 c.c. of the
urine to boiling, adding a dilute solution (2 per cent.) of acetic acid by
drops as long as the precipitate seems to be increased. Filter through
a weighed filter. Wash the precipitate on the filter with hot water,
then with hot alcohol, and finally with ether. Dry in an air-bath at
110° C., and weigh between watch-glasses of known weight.
(6) Esbach's Method. — Esbach's reagent is made by dissolving
10 grammes of picric acid and 20 grammes of citric acid in boiling
water (800 or 900 c.c.), and then making up the volume to a litre. The
so-called albuminimeter is simply a strong glass tube graduated and
marked in a certain way. Fill the tube up to the mark U with the
urine. Then add the reagent up to the mark R. Close the tube with
the rubber cork, and invert it a dozen times without shaking. Set the
tube aside for twenty-four hours, then read off the graduation on the
tube which corresponds with the top of the precipitate. The figures
indicate the number of grammes of dry protein in a litre of the urine.
Suppose the top of the sediment is at 4, this will indicate 4 grammes per
litre, or 0-4 per cent. The method is of some clinical importance, owing
to its simplicity, although it is, of course, not very accurate.
14. Sugar — (i) Qualitative Tests — (a) Trommer's Test (p. 10). — It is to
be remarked that some substances present in small amount in normal
urine reduce cupric sulphate — e.g., uric acid (present as urates) and
kreatinin — but although a normal urine may thus decolourize the
copper solution, it rarely causes so much reduction that a yellow or red
precipitate is formed, as is the case in diabetic urine. Glycuronic acid
(p. 482) also reduces cupric salts, as does alcapton or homogentisinic
acid, a substance found in rare cases in disease (p. 483).
(6) Fehling's Test. — Fehling's solution (p. 526) is brought to the boil ill
a test-tube, a little of the urine then added, and the change of colour
noted. Benedict's modification of Fehling's solution may also be used.
It has the advantage that it keeps indefinitely, and therefore is always
ready for use, and is also said to be more delicate.
(c) Phenyl-Hydrazine Test. — This test depends upon the fact that
phenyl-hydrazine forms with sugars such as glucose (dextrose), maltose,
isomaltose, etc., but not with cane-sugar, characteristic crystalline
substances (phenyl-glucosazone, phenyl-maltosazone, etc.) which can
be recognized under the microscope, and are distinguished from each
other by melting at different temperatures. Phenyl-glucosazone
526
EXCRETION
melts at 205° C. To perform the test for dextrose in the
urine, proceed thus: Put 5 c.c. of urine in a test-tube, add I decigramme
of hydrochlorate of phenyl-hydrazine and 2 decigrammes of sodium
acetate. It is sufficiently accurate to add as much phenyl-hydrazine
as will lie on a sixpence (or a dime) and twice as much sodium acetate.
Heat the test-tube in a boiling water-bath for half an hour. Then cool
at the tap and examine the deposit under the microscope for the yellow
phenyl-glucosazone crystals (Fig. 196). Sometimes the osazone pre-
cipitate is amorphous. If this should be the case, the precipitate, if no
crystals can be seen, must be dissolved in hot alcohol. The solution is
then diluted with water and the alcohol boiled off, when the osazone,
if any be present, will crystallize out.
Very minute traces of sugar can be
detected in this way (as little as oa per
cent, in urine). Often in normal urine
yellow crystals are deposited during
the first fifteen minutes' heating.
They must not be mistaken for gluco-
sazone. They probably consist of a
compound of glycuronic acid and
phenyl-hydrazine. They are changed
as the heating goes on into an amor-
phous brownish - yellow precipitate
(Abel).
(d) The Yeast Test is an importanl
confirmatory test for distinguishing
the fermentable sugars from other re-
ducing substances, but it is not very
delicate, and will with difficulty detect
sugar when less than 0-5 per cent, is
present. It can be performed thus:
A little yeast (the tablets of com-
pressed yeast do very well) is added
to a test-tube half filled with urine.
The test-tube is then filled up with
mercury, closed with the thumb, and
inverted over a dish containing mer-
cury. The dish may be placed on the
top of a water-bath whose temperature
is about 40° C. After twenty-four
hours the sugar will have been broken
up into alcohol and carbon dioxide. The latter will have collected
above the mercury in the test-tube, and the former will be present in
the urine. The tests for sugar will either be negative or will be less
distinct than before. A control test-tube containing water and yeast
should also be set up, as impurities in the yeast sometimes yield a small
amount of carbon dioxide. Specially- constructed tubes are also often
used for performing the test.
(2) Quantitative Estimation of Sugar in Urine. — (a) Volumetrically,
the sugar can be estimated by titration with Fehling's solution. As
this does not keep well, two solutions containing its ingredients should
be kept separately and mixed when required. Solution I.: Dissolve
34-64 grammes pure cupric sulphate in distilled water, and make up the
volume to 500 c.c. Solution II.: Dissolve 173 grammes Rochelle salt
in 400 c.c. of water, add to this 51-6 grammes sodium hydroxide, and
make up the volume with water to 500 c.c. Keep in well-stoppered
Fig. 196. — Phenyl-Glucosazone and
Phenyl-Maltosazone Crystals (Mac-
leod). The phenyl - glucosazone
crystals are in the upper part of
the figure, the phenyl-maltosazone
in the lower.
PRACTICAL EXERCISES 527
bottles in the dark. For use, mix together equal volumes of the two
solutions. Ten c.c. of this mixture is reduced by 0-05 gramme dextrose.
To estimate the sugar in urine, put 10 c.c. of the mixture into a porcelain
capsule or glass flask, and dilute it four or five times with distilled water.
Dilute some of the urine, say ten or twenty times, according to the
quantity of sugar indicated by a rough determination. Run the
diluted urine from a burette into the Fehling's solution, bringing it to
the boil each time urine is added, until, on allowing the precipitate
to settle, the blue colour is seen to have entirely disappeared from the
supernatant liquid. The observation of the colour must be made while
the liquid is still hot. Benedict's modification of Fehling's solution*
may also be employed.
Suppose that 10 c.c. of Fehling's solution is decolourized by 20 c.c.
of the ten-times diluted urine. Then 2 c.c. of the original urine contains
0-5 gramme dextrose. If the urine of the twenty-four hours (from
which this sample is assumed to have been taken) amounts to 4,000 c.c.,
the patient will have passed 0-05x2,000=100 grammes sugar, in
twenty-four hours.
(6) The polarimeter affords a rapid and, with practice, a delicate
means of estimating the quantity of sugar in pure and colourless solu-
tions, but diabetic urine must in general be first decolourized by adding
lead acetate and filtering off the precipitate. What is measured is the
amount by which the plane of polarization of a ray of polarized light of
given wave-length (say sodium light) is rotated when it passes through
a layer of the urine or other optically active solution of known thickness.
Let a be the observed angle of rotation, / the length in decimetres of
the tube containing the solution, w the number of grammes of the
optically active substance per c.c. of solution, and (a)D the specific
rotation of the substance for light of the wave-length of the part of the
spectrum corresponding to the D line (i.e., the amount of rotation
expressed in degrees which is produced by a layer of the substance
I decimetre thick, when the solution contains i gramme of it per c.c.).
Then (a)D = ± — -.. In this equation a and / are known from direct
measurement; (a)D has been determined once for^all for most of the
important active substances, and therefore w is easily calculated. For
dextrose (a)D may be taken as 52-6°. It varies somewhat with the
concentration, but for most investigations on the urine these variations
may be neglected.
It is not possible to describe here the numerous forms of polarimeter
that are in use. Those constructed on what is called the ' half -shadow '
system (Fig. 197) give sufficiently satisfactory results. A half -shadow
polarimeter consists, like other polarimeters, of a fixed Nicol's prism
(the polarizer), and a nicol capable of rotation (the analyzer). In
addition, there is an arrangement which rotates by a definite angle the
plane of polarization in one -half of the field, but not in the other —
e.g., a small nicol occupying only half of the field. In the zero position
of the analyzer, both halves of the field are equally dark. The solution
to be investigated is placed in a tube of known length, the ends of which
* It contains 17" 3 grammes of cupric sulphate, I73'o grammes of sodium
citrate, ioo'o grammes of anhydrous sodium carbonate made up with
distilled water exactly to one litre. In making the solution the citrate and
carbonate are dissolved with the aid of heat in about 600 c.c. ot water, and
then made up to about 800 c.c. The cupric sulphate is dissolved in about
too or 150 c.c. of water and added to the other solution, the whole being then
made up to a litre.
5*8
EXCRETION
are closed by glass discs secured by brass screw caps. The glass discs
must be slid on, so as to exclude all air. The tube having been intro-
duced between the polarizer and analyzer, the sharp vertical line which
indicates the division between the two half-fields is focussed with the
eye-piece, and then the analyzer is rotated till the two halves are again
equally shadowed. The angle of rotation, a, is read off on the graduated
arc, which is provided with a vernier.
Pentoses reduce Fehling's solution, but do not give the yeast test.
They give the following characteristic tests, which may be performed
with gum arabic, a substance containing arabinose, one of the pentoses:
(i) Phloroglucin Reaction. — Warm in a test-tube some pure concen-
trated hydrochloric acid to which an equal volume of distilled water
has been added. Add phloroglucin until a little remains undissolved.
Fig. 197. — Mitscherlich's Polarimeter. (Half-shadow instrument.) (Simple form.)
Add a small quantity of gum arabic, and keep the test-tube in a water-
bath at 100° C. The solution becomes cherry-red, and a precipitate
gradually separates, which may be dissolved in amyl alcohol. The
solution shows with the spectroscope a band between D and E.
(2) Or tin Reaction. — Use orcin instead of phloroglucin in (i). The
solution becomes reddish-blue on warming, and shows a band between
C and D, near D. The colour quickly changes from violet to blue, red,
and finally green. A bluish-green precipitate separates, which is
soluble in amyl alcohol. Glycuronic acid gives all the above reactions
of pentoses.
Bile-Salts (Hay's Test). — Put a little finely-divided sulphur, in the
form of flowers of sulphur, on the top of a glass of urine. If bile-salts
are present the sulphur will sink to the bottom. If there are no bile-
PRACTICAL EXERCISES 5*9
Salts il will float on the top. The difference is due to an alteration in
the surface tension of the urine produced by the bile-salts. We must
exclude the presence of acetic acid, alcohol, ether, chloroform, turpen-
tine, benzine and its derivatives, phenol and its derivatives, anilin and
soaps, all of which also cause such an alteration in the surface tension
of urine that the sulphur sinks to the bottom. The urine should be
fresh, and if it has to be kept it should be preserved from decomposition
by cyanide of mercury, which does not alter the surface tension. The
reaction has the great advantage over other tests of being easily carried
out at the bedside.
Acetone — (i) Legal' s Test (Rothera's modification). — To 5 to 10 c.c.
of the acetone-containing urine add enough ammonium sulphate crystals
to form a layer at the bottom of the test-tube, then 2 or 3 drops cf
a fresh 5 per cent, solution of sodium nitro-prusside and i to 2 c.c. of
strong ammonia. The development of a colour like that of perman-
ganate of potassium, often in the form of a ring a little above the
undissolved salt, indicates the presence of acetone. The reaction must
not be declared negative till half an hour has elapsed. The colour
slowly fades.
(2) Where there is doubt as to the presence of acetone, it is best first
to distil it over. Put 250 to 500 c.c. of the urine suspected to contain
acetone into a litre flask. Add a few c.c. of phosphoric acid; connect
the flask with a worm, and distil over the urine into a small flask.
For qualitative tests it is best to collect only the first 20 to 30 c.c.,
as most of the acetone is contained in this. Test the distillate for
acetone by (i) or by
Lieben's Test. — To a few c.c. of the distillate in a test-tube add a few
drops of solution of iodine in potassium iodide, and then sodium or
potassium hydroxide. A precipitate of yellow iodoform crystals (six-
sided tables) is thrown down if acetone be present. Examine them
under the microscope. On heating, the odour of iodoform may be
recognized. If the precipitate is amorphous it may be dissolved in
ether (free from alcohol), which is allowed to evaporate on a slide,
when crystals may be obtained.
Determination of the Freezing-Point of Urine.* — Study Beckmann's
apparatus shown in Fig. 171, p. 427. Note the large thermometer D
graduated in hundredths of a degree centigrade. It is inserted through
a rubber cork into the inner test-tube A. A platinum wire, F, bent
at the lower end into a circle or a spiral, which passes easily up and
down between the bulb of the thermometer and the tube, serves to stir
the urine. The thermometer must be so supported by the rubber
cork that the bulb is in the axis of the tube and a centimetre or two from
the bottom of it. The side-piece E on the tube A is not absolutely
necessary, but it is convenient for ' inoculating ' the urine with a crystal
of ice at the proper time. A passes through a rubber cork into a shorter
and wider outer glass tube B. The space between A and B serves as a
badly conducting mantle, which prevents too rapid cooling of the
contents of A. B passes through a hole in the metal or wooden cover
of a strong glass jar, C, which contains the freezing mixture. B should
fit the hole so tightly that it does not bob up out of the mixture when
A is removed. In C is a stirrear, G, of strong copper wire, the end of
which passes through the lid. This serves to stir up the freezing
mixture from time to time.
Pulverize some ice by pounding it in a strong wooden box with a
heavy piece of wood. Take the inner tube with the thermometer out
of the apparatus. It is convenient to take the thermometer out of the
* This is not often of clinical value, but it affords an opportunity for the
student to practise a method of great importance in physiology.
34
530 EXCRETION
tube, and to hang it up carefully on a stand by means of a fine flexible
copper wire passing through the eye. The rubber cork can be taken
out with the thermometer, and the platinum wire also, the bent free
end of the latter supporting it in the cork, or it may be fastened tempor-
arily to the thermometer stem by a small rubber band, which is slid
up over the cork when the thermometer is reinserted. Tube A can be
set temporarily in a specially heavy test-tube rack. Remove the lid
of C, and with it tube B. Now put ice and salt alternately into C until
it is nearly full, mixing them up well. Add some cold water from the
tap till the stirrer G can move freely up and down in the mixture. For
very exact work the temperature of the freezing mixture must not be
more than a few degrees below the freezing-point of the liquid which is
being examined. Put on the lid, and immerse tube B. Into A, which
must be perfectly clean, put enough pure distilled water to fully cover
the bulb of the thermometer, and introduce the latter. For ordinary
purposes distilled water previously boiled to expel the carbon dioxide,
and then cooled in a stoppered flask, is sufficiently pure. Immerse A
directly in the freezing mixture through the hole by which G comes out,
or through a separate hole (not shown in the figure) till some ice has
formed in the water. Take A out of the mixture, wipe it with a cloth,
and hold the lower part of it in the hand till nearly the whole of the
ice has melted. If there is a cake of ice at the bottom, see that it is
displaced by the platinum stirrer. A trace of ice being still left floating
in the water, place A in B, and allow the temperature to fall to a few
tenths of a degree below the freezing-point you expect to get, as deter-
mined by a previous rough experiment. The freezing mixture is
stirred up occasionally. The meniscus of the thermometer is to be
carefully followed, as it goes on falling, by means of a weak hand lens.
Now stir the water in A briskly. Suddenly it will be seen that the
mercury begins to rise. Keep stirring with the platinum wire, and
read off the maximum height of the mercury, at which it is stationary
for some time. The temperature can be estimated between the gradu-
ations to thousandths of a degree. Take out A, and observe the fine
ice crystals in the water. Heat A in the hand as before till nearly all
the ice has disappeared ; then replace A in B, and make another freezing-
point determination. A third one may also be made, and the mean
of the three readings taken.
Take out the thermometer, and dry it and the platinum wire with
clean filter-paper, or dip them in some of the urine, which is then thrown
away. Dry A or rinse it with urine. Then make a determination of
the freezing-point of the urine in the same way as was done with the
water. The freezing-point of the urine will lie much lower on the scale.
Instead of freezing the liquid first and then leaving a little ice in it
when A is placed in B, A may be put into B before any ice has formed.
Cooling is then allowed to go on with gentle stirring to a few tenths of
a degree below the anticipated freezing-point. A small crystal of
clean dry ice is then introduced through the side-piece on a clean
splinter of wood or the loop of a cooled platinum wire, the end of which
passes through a piece of cork, by which it is held to prevent conduction
of heat. The platinum stirrer can be raised to receive the crystal. The
liquid is now vigorously stirred ; freezing occurs, and the observation is
made as before.
Instead of the above method, the liquid may first be cooled directly
in the freezing mixture, but not so much that ice forms. A is then put
in B, and cooling allowed to go on while it is being stirred. When it
has been undercooled to a certain extent — i.e., cooled below its freezing-
point — the vigour of the stirring is increased. Ice forms suddenly, as
before, and the temperature rises to the freezing-point. With urine
PRACTICAL EXERCISES
531
this method is sufficiently satisfactory, but it is not usually easy to get
freezing of the distilled water till the undercooling is considerable, and
it has been shown that this introduces some error.
Suppose the freezing-point of the distilled water on the scale of the
thermometer was 5-245 and that of the urine 3-625°, the value of A
for the urine is 1-620°. Since for most purposes it is sufficient to fix
the second decimal point, much smaller and less expensive thermometers
than the ordinary Beckmann may be employed.
In the same way the freezing-point of blood-serum (or blood), bile,
and other physiological liquids can be determined.
Systematic Examination of Urine. — In examining urine, it is con-
venient to adopt a regular plan, so as to avoid the risk of overlooking
anything of importance. The following simple scheme may serve as
an example; but no routine should be slavishly followed, the object
being to get at the important facts with the minimum of labour. More
extensive information must be sought in the treatises on examination
of the urine for clinical purposes.
1. Anything peculiar in colour or smell ? If the colour suggests
blood, examine with spectroscope, haemin test, guaiacum test (pp. 76,
272) ; if it suggests bile, test for bile-pigments by Gmelin's test (p. 462),
and for bile-salts by Pettenkofer's test (p. 462) and by Hay's test
(pp. 462, 528).
2. Reaction.
3. Sediment or not ? Sediment may be procured by letting the
urine stand in a conical glass, or in a few minutes by the centrifuge.
.If the appearance of the sediment suggests anything more than a little
mucus, examine with the microscope. The sediment may contain
organized or unorganized deposits.
Organized Sediments. — (a) Red blood-corpuscles (considerably altered
if they have come from the upper part of the urinary tract).
(6) Leucocytes. A few are present in health. A large number
indicates pus. When pus is present the sediment may be white to the
naked eye.
(c) Epithelium from the bladder, ureters, pelvis of the kidney or the
renal tubules. A few squamous epithelial cells from the urethra are
always present in normal urine.
(d) Tube casts.
(e) Spermatozoa (occasional).
(/) Bacteria.
(g) Parasites (rare).
(h) Portions of tumours (rare).
Unorganized Sediments.
IN ACID URINE.
Uric Acid. — Crystals coloured
brownish - yellow with urinary
pigment. Various shapes, espe-
cially oval ' whetstones,' rhom-
bic tables, and elongated crystals,
often in bundles (Fig. 177).
Urates. — Usually amorphous, in
the form of fine granules, often
tinged with urinary pigment,
sometimes brick-red. Soluble on
heating. On addition of acids
(including acetic acid) they dis-
IN ALKALINE URINE.
Triple Phosphate. — Clear, col-
ourless, coffin - lid or knife - rest
crystals. Also deposited in the
form of feathery stars (Fig. 179).
Calcium Hydrogen Phosphate
(' stellar ' phosphate), CaHPO4. —
Crystals often wedge-shaped and
arranged in rosettes. May also
occur in a dumb-bell form. (A
phosphate of calcium is also occa-
sionally seen in weakly acid urine.)
(Fig. 1 8 1, p. 479.)
532
EXCRETION
Unorganized Sediments (continued) — >
IN ACID URINE.
solve and uric acid cystals appear
in their place. Acid urate of
sodium and of ammonium occa-
sionally found in the crystalline
form (rosettes of needles) .
Calcium Oxalate. — Octahedral,
' envelope ' crystals, not coloured.
Insoluble in acetic acid. Soluble
in hydrochloric acid (Fig. 178,
p. 478).
Cystin. — Hexagonal plates.
Rare (Fig. i8o,p. 4 ;•.;).
Leucin and Ty rosin (Figs. 186,
187, p. 488). — Rare. Also found
in alkaline urine, but rarely.
Triple Phosphate. — Sometimes
found in weakly acid urine.
IN ALKALINE URINE.
Calcium Phosphate, Ca3(PO4)2 •—
Amorphous.
Magnesium Phosphate . — Long
rhombic tablets, which are dis-
solved at the edges by ammonium
carbonate solution, unlike triple
phosphate. All the above are
soluble in acetic acid without
effervescence.
Calcium Carbonate. — Small
spherical or dumb - bell - shaped
bodies soluble in acetic acid with
effervescence.
Ammonium Urate. — Dark balls,
often covered with spines. Soluble
in acetic or hydrochloric acid,
with formation of uric acid crys-
tals (Fig. 182, p. 479).
4. Specific gravity.
5. Quantity of urine in twenty-four hours. If the quantity is
abnormally large and the specific gravity high, test for sugar.
6. Inorganic constituents not generally of clinical importance, but
in special diseases they should be examined — e.g., chlorides in pneu-
monia.
7. Normal organic constituents. Sometimes quantitative estima-
tion of urea or total nitrogen in fever, and in diabetes and Bright's
disease.
8. Chemical examination for abnormal organic constituents, especi-
ally albumin and sugar.
Albumin. — (i) Heat to boiling some of the urine in a test-tube. A
precipitate insoluble on addition of a few drops of acetic acid consists
of coagulable protein. A precipitate soluble in acetic acid consists of
earthy phosphates.
(2) Heller's test. Put some strong nitric acid in a test-tube and
run on to it some urine. A white ring indicates protein.
A very rough quantitative estimation may be made by the method
of Esbach (p. 525).
Sugar. — (i) Trommer's test. (Fehling's solution may be used.) I*
the result is indecisive —
(2) Phenyl-hydrazine test (p. 525)-
(3) In case of doubt confirm by yeast test.
A quantitative estimation may be made with Fehling's solution or
the polarimeter.
CHAPTER X
METABOLISM, NUTRITION AND DIETETICS
WE return now to the products of digestion as they are absorbed
from the alimentary canal, and, still assuming a typical diet con-
taining carbo-hydrates, fats, and proteins, we have to ask, What
is the fate of each of these classes of proximate principles in the
body ? what does each contribute to the ensemble of vital activity ?
It will be best, first of all, to give to these questions what roughly
qualitative answer is possible, then to look at metabolism in its
quantitative relations, and lastly to focus our information upon
some of the practical problems of dietetics.
SECTION I. — METABOLISM OF CARBO-HYDRATES — GLYCOGEN.
The carbo-hydrates of the food, passing into the blood of the
portal vein in the form of dextrose, are in part arrested in the liver,
and stored up as glycogen in the hepatic cells, to be gradually given
out again as sugar in the intervals of digestion. The proof of this
statement is as follows:
Sugar is arrested in the liver, for during digestion, especially of a
meal rich in carbo-hydrates, the blood of the portal contains more
sugar than that of the hepatic vein. Popielski, on the basis of
experiments in which he fed with known quantities of sugar dogs
whose inferior vena cava and portal vein had been united by an
Eck's fistula, and determined the amount of sugar which passed
into the urine, estimates the quantity of sugar kept back by the
liver at from 12 to 20 per cent, of the whole. In the liver there
exists a store of sugar-producing material from which sugar is
gradually given off to the blood, for in the intervals of digestion the
blood of the hepatic veins contains more dextrose (2 parts per 1,000)
than the mixed blood of the body or than that of the portal vein
(about i part per 1,000). When the circulation through the liver
is cut off in the goose, the blood rapidly becomes free, or nearly free,
from sugar (Minkowski). And a similar result follows such inter-
ference with the hepatic circulation as is caused by the ligation of
the three chief arteries of the intestine in the dog, even when the
animal has been previously made diabetic by excision of the pancreas
(p. 636).
533-
534 METABOLISM, NUTRITION AND DIETETICS
The nature of the sugar-forming substance is made clear by the
following experiments: (i) A rabbit after a large carbo-hydrate
meal, of carrots for instance, is killed and its liver rapidly excised,
cut into small pieces, and thrown into acidulated boiling water.
After being boiled for a few minutes, the pieces of liver are rubbed
up in a mortar and again boiled in the same water. The opalescent
aqueous extract is filtered off from the coagulated proteins. No
sugar, or only traces of it, are found in this extract; but another
carbo-hydrate, glycogen, a polysaccharide giving a port-wine
colour with iodine and capable of ready conversion into sugar by
amylolytic ferments, is present in large amount. (See Practical
Exercises, p. 715.)
(2) The liver after the death of the animal is left for a time in
situ, or, if excised, is kept at a temperature of 35° to 40° C, or for
a longer period at a lower temperature; it is then treated exactly
as before, but no glycogen, or comparatively little, can now be
obtained from it, although sugar (dextrose) is abundant. The
inference plainly is that after death the hepatic glycogen is con-
verted into dextrose by some influence which is restrained or de-
stroyed by boiling. This transformation might theoretically be
due to an unformed ferment or to the direct action of the liver-cells,
for both unformed ferments and living tissue elements are destroyed
at the temperature of boiling water. It ha.- been clearly shown
that the action is brought about by a diastatic enzyme, which some
writers call glycogenase, for it readily occurs when the minced liver
is mixed with chloroform water, and chloroform kills all living
tissues. Although blood contains a diastase in small amount, the
change does not depend essentially upon this, since the glycogen
also undergoes hydrolysis (glycogenolysis) to dextrose when all the
blood has been washed out of the organ. Lymph also contains a
diastase, but there is evidence that the post-mortem glycogenolysis
is chiefly due to an enzyme contained in the hepatic cells (an endo-
enzyme) (Macleod). The diastases in the blood and lymph seem
to be ' discards ' of the tissues which are on the way to destruction
or elimination (Carlson). The post-mortem change is to be regarded
as an index of a similar action which goes on during life: sugar in
the intact body is changed into glycogen ; glycogen is constantly
being changed into sugar. There is no reason to doubt that here,
too, the hydrolysis is effected by the endo-enzyme. It might be
supposed, indeed, that the adjustment of the two processes glyco-
gcnesis and glycogenolysis is simply a matter of the alteration of
the equilibrium in a reversible reaction (p. 338), according to
whether the dextrose content of the blood tends to rise or fall. If
the concentration of dextrose in the blood is increased, more dex-
trose might be expected to ' diffuse ' into the hepatic cells, whose
content of dextrose in proportion to glycogen would increase till
the equilibrium was restored by the conversion of the excess of
METABOLISM OF CARBO-HYDRATES— GLYCOGEN 533
sugar into glycogen. Contrariwise, a diminution in the dextrose
content of the blood might be expected to lead to diffusion of
dextrose out of the liver-cells, and a consequent acceleration of the
hydrolysis of the glycogen. We have already learnt, however, that
in physiology — above all, perhaps, in the physiology of the glands
— ' simple ' explanations are usually suspect. And when we come to
study those conditions in which, as a consequence of the derange-
ment of the mechanisms which regulate the carbo-hydrate metabo-
lism, sugar appears in the urine, it will be seen that the matter is
more complicated. For one thing, the nervous system seems to
take a hand in the regulation, and where the nervous system takes
a hand things are generally doing which the experienced physiologist
does not expect to be simple. We may be certain, as in the case of
the intracellular proteolytic ferments, that the vital action of the
hepatic cells is a most important factor in controlling the rate of
production of the ferment, and therefore its concentration in rela-
tion to that of the substrate and the rate at which it works.
(3) With the microscope, glycogeri, or at least a substance which
is very nearly akin to it, which very readily yields it, and which
gives the characteristic port-wine colour with iodine, can be actually
seen in the liver-cells. The liver of a rabbit or dog which has been
fed on a diet containing much carbo-hydrate is large, soft, and very
easily torn. Its large size is due to the loading of the cells with a
hyaline material, which gives the iodine reaction of glycogen, and
is dissolved out by water, leaving empty spaces in a network of cell-
substance. If the animal, after a period of starvation, has been
fed on protein alone, less glycogen is found in the shrunken liver-
cells; if the diet has been wholly fatty, little or no glycogen at all
may be found. Glycogen can even be formed by an excised liver
when blood containing dextrose is circulated through it.
A fact of great interest recently demonstrated is that in animals
where the mobilization of the hepatic glycogeri is accelerated (as
in rabbits after puncture of the medulla), glycogen in the form of
granules and small masses can be seen in the blood capillaries
(or rather sinusoids) between the liver cells, and in the sublobular
veins (Huber and Macleod). Chemical evidence has also been
obtained of the presence of a glycogen-like polysaccharide in the
blood leaving the liver.
Formation of Glycogen from Protein. — In the liver-cells of the
frog in winter-time a great deal of this hyaline material — this
glycogen, or perhaps loose glycogen compound — is present; in
summer, much less. The difference is remarkable if we con-
sider that in winter frogs have no food for months, while summer
is their feeding-time; and at first it seems inconsistent with the
doctrine that the hepatic glycogen is a store laid up from surplus
sugar, which might otherwise be swept into the general circulation
and excreted by the kidneys. It has been found, however, that
536 METABOLISM, NUTRITION AND DIETETICS
the quantity of glycogen is greatest in autumn at the beginning of
the winter-sleep, and slowly diminishes as the winter passes on,
to fall abruptly with the renewal of the activity of the animal in
the spring. The glycogen present at any moment is, therefore,
believed to be a residue, which represents the excess of glycogen
formed over glycogen used up; and the amount is larger in winter,
not because more is manufactured than in summer, but because
less is consumed. It is possible, indeed, to produce the ' summer '
condition of the hepatic cells merely by raising the temperature of
the air in which a winter frog lives ; at 20° or 25° C. glycogen dis-
appears from its liver. Conversely, if a summer frog is artificially
cooled, a certain amount of glycogen accumulates in the liver. The
meaning of this seems to be that at a low temperature, when the
wheels of life are clogged and metabolism is slow, some substance,
probably dextrose, is produced in the body from proteins in greater
amount than can be used up, and that the surplus is stored as
glycogen; just as in plants starch is put by as a reserve which can
be drawn upon — which can be converted into sugar — when the
need arises. That carbo-hydrates may be formed from proteins
(or their constituent amino-acids) has been shown in various ways —
for example, by feeding dogs with almost pure protein (casein) after
the production of permanent glycosuria by removal of the pancreas
(p. 636). To induce the animal to take the casein it had to be
mixed with a certain amount of butter, or serum, or meat extract.
The amount of sugar excreted was much more than could possibly
have come from the glycogen originally present in the animal's body,
computing it on the most generous scale (41 grammes per kilo-
gramme of body-weight, according to Pfliiger), or from free carbo-
hydrate present in traces in the food, or as prosthetic groups (p. 2)
in the ingested protein. That the source of the sugar was protein
and not fat was indicated by the fact that when the amount of
protein food was increased, the dextrose and the nitrogen excreted
increased proportionally (see also p. 538)-
Glycogen-Formers. — As true glycogen-formeis in the higher
animals — that is, compounds whose elements (particularly the
carbon) actually enter into the composition of the glycogen mole-
cule— may be mentioned such substances as proteins (including
gelatin), the fermentable sugars, and glycerin. In the case of
proteins it is, of course, not the entire molecule which is transformed
bodily into glycogen, but amino-acids yielded by them, or dextrose
derived from the amino-acids. The liver is of itself capable of
dealing only with the dextrose, and not with the amino-acids. At
least, when the isolated liver (of the tortoise) is perfused with
blood containing amino-acids no increase in the glycogen of the
liver occurs. When glycerin is added to the blood the glycogen
content of the liver is very distinctly increased. Glycerin is a tri-
valent alcohol (C3H8O3) whose aldehyde, obtained from it by gentle
METABOLISM OF CARBO-HYDRATES— GLYCOGEN 537
oxidation, is glycerose (C3H6O3), a substance with the typical
properties of a sugar. In the laboratory it has been shown that
two molecules of glycerose can be combined to form one molecule of
sugar of the hexose type with six carbon atoms (C6H12O6) . A similar
transformation is accomplished in the liver, and then a number of
the monosaccharide molecules (C6H12O6) are condensed with loss of
water to form glycogen. Thus, w(C6H12O6) — «H2O = (C6H10O5)w.
Since glycerin is a normal product of the hydrolysis of fats, the
possibility that the fats of the food may contribute through their
glycerin component to glycogen formation must be admitted. The
monosaccharides dextrose, levulose, and galactose gave a similar
result, while the disaccharides cane-sugar and lactose caused no
increase in the glycogen of the perfused liver, since the liver contains
no ferment capable of splitting them into monosaccharides. And
although the first step in the linking of the monosaccharide mole-
cules would seem to be the formation of a disaccharide such as
maltose, the glycogen molecule must apparently be built up from
single ' bricks,' the monosaccharides, and cannot be constructed
from bricks which are already coupled in pairs, the disaccharides.
Of course, since the disaccharides are hydrolysed in the digestive
tube to simple sugars, they are to be reckoned with the true glycogen-
formers, for in the intact body they are presented to the hepatic
cells in the form of monosaccharides. It is probable that levulose
and galactose are first changed into dextrose.
By the action of alkalies such structurally related sugars can easily
be transformed into each other. Thus dextrose is an aldehyde of an
alcohol with six carbon atoms, and levulose the corresponding keto-
hexose.
By oxidizing the alcohol we get an aldehyde or a ketone, according
to whether a primary alcohol group (CHa.OH) or a secondary group
(CH.OH) is oxidized, with the loss of two atoms of hydrogen. The
aldehyde is characterized by the presence of the group £\v> the
ketone by the group CO. Both the aldehyde and the ketone are
sugars, and since each contains six carbon atoms, they are both sugars
of the group known as ' hexoses.' Dextrose, being not only a hexose
but an aldehyde, may be called an ' aldohexose,' and levulose, being
not only a hexose but a ketone, a ' ketohexose.'
CHa.OH C/2 CHa.OH
I lx I
CH.OH CH.OH CO
CH.(
CH.OH CH.OH CH.OH
CH.OH CH.OH CH.OH
CH.OH CH.OH CH.OH
CHa.OH CH2.OH CH2.OH
6-valent alcohol. Aldehyde. Ketone,
538 METABOLISM, NUTRITION AND DIETETICS
That levulose can be changed into dextrose in the body is indi-
cated by the observation that after extirpation of the pancreas in
dogs the administration of levulose is followed by an increase in
the excretion of dextrose nearly equal to the amount of levulose
ingested. It is also stated that, when the surviving liver of a
normal dog is perfused with a suspension of washed blood-corpuscles
to which levulose has been added, dextrose accumulates in the blood
and levulose disappears from it.
It has not hitherto been proved that the fatty acid component of
the food fats can be converted into glycogen. But a fatty acid,
propionic acid, is capable of complete transformation into dextrose
when given either by the mouth or subcutaneously to dogs under
the influence of phlorhizin (Ringer) . Many other bodies are known
to influence the formation of glycogen by ' sparing ' substances
which are true glycogen-producers, but their carbon does not actu-
ally take its place in the glycogen molecule. It has been shown that
proteins can directly form glycogen or sugar apart from carbo-
hydrate groups contained in the protein molecule. For the proteins
of meat, gelatin, and casein are capable of forming 60 per cent, of
their own weight of dextrose in diabetic metabolism, and even the
end-products of pancreatic digestion of meat yield so much sugar
that the greater part of it must have come from the amino-bodies,
and not from a sugar-group in the protein. When given to dogs
with total phlorhizin glycosuria (p. 551), glycin and alanin are
completely, glutamic and aspartic acids in great part (corresponding
to about three carbon atoms of their respective molecules), converted
into dextrose (Lusk and Ringer), and there is no reason to doubt
that when such substances are produced by hydrolysis of protein
in the normal body, and are not all utilized in rebuilding the bio-
plasm, a portion of the surplus, after deamidization, can be trans-
formed into glycogen.
Extra-Hepatic Glycogen. — While the liver in the adult (con-
taining as it does from 2 to 10 per cent, of glycogen, or even, with
a diet rich in sugar or starch, more than 18 per cent.) may be looked
upon as the main storehouse of surplus carbo-hydrate, depots of
glycogen are formed, both in adult and fcetal life, in other situations
where the strain of function or of growth is exceptionally heavy —
in the muscles of the adult (0-3 to 0-5 per cent, of the moist skeletal
muscle, or on a carbo-hydrate regimen 0-7 to 3-7 per cent.), in the
placenta, in many developing organs in the embryo (muscles, lungs,
epithelium of the trachea, oesophagus, intestine, ureter, pelvis of
kidney, and renal tubules). The foetus, however, is not, compared
with the adult, especially rich in glycogen. In the adult under
favourable circumstances the absolute amount of glycogen in the
muscles may be several times greater than that in the liver, and
METABOLISM OF CARBO-HYDRATES— GLYCOGEN 539
usually the hepatic glycogen makes up considerably less than half
the total glycogen of the body. That the muscles do not derive
their glycogen by the migration of hepatic glycogen, but can them-
selves form it from dextrose, has been shown by injecting that sugar
subcutaneously into frogs after excision of the liver. The muscle
glycogen was found to be increased.
Function and Fate of the Glycogen. — The glycogen store of the
liver fulfils a different function from that of the muscles. This is
indicated by the fact that when dogs, after being put on a given diet
for two or three days, are starved for a time, and then put again on
the original diet, the hepatic and the muscular glycogen behave
differently at first during the period of re-alimentation. While
glycogen accumulates in the liver in greater quantity than under
normal conditions of nutrition, in the muscles it at first accumulates
much less rapidly than normally. This is entirely in accordance
with the view that the hepatic glycogen store has for its great func-
tion the regulation of the sugar content of the blood in the interest
of all the tissues, while the glycogen store of the muscles and other
tissues is mainly in the interest of their own nutrition and a source
of energy for their own work. This does not imply that, when sugar
is being absorbed in quantities too great for the liver to deal with
after the current needs of the tissues have been satisfied, they do
not add to their glycogen reserves. There is every reason to suppose
that they do so, and thus act as a subsidiary regulating mechanism,
although a less elastic one than that supplied by the liver. A third
way in which a portion of the surplus sugar can be stored is in the
form of fat.
When a fasting dog is made to do severe muscular work, the
greater part of the glycogen soon disappears from its liver. When
a dog is starved, but allowed to remain at rest, the glycogen still
markedly diminishes, although it takes a longer time; and at a
period when there is still plenty of fat in the body, there may be
only a trace of hepatic glycogen left. The glycogen which is usually
contained in the skeletal muscles also diminishes very rapidly in the
first days of hunger, but the heart contains the normal amount of
glycogen at a time when the proportion in the skeletal muscles has
sunk to Jfr to -£$ of the normal.
These facts have been taken to indicate that glycogen and the sugar
formed from it are the readiest resources of the starving and working
organism, for the transformation of chemical energy into heat and
mechanical work. To borrow a financial simile, the fat of the body
has sometimes been compared to a good, but rather inactive security,
which can only be gradually realized; its organ-proteins to long-date
bills, which will be discounted sparingly and almost with a grudge;
its glycogen, its carbo-hydrate reserves, to consols, which can be turned
into money at an hour's warning. Glycogen, on this view, is especiallj
54° METABOLISM, NUTRITION AND DIETETICS
drawn upon for a sudden demand, fat for a steady drain, tissue-protein
for a life-and-death struggle. While there may be some such difference
in the tenacity with which the different kinds of reserve material are
held back from consumption when the floating supplies are wearing
low, modern investigation tends to the conclusion that the interchange-
ability of the various groups of nutritive substances is greater than
had been supposed, and that in the long-run the cells — in normal cir-
cumstances at least — never work without dextrose, even after the
glycogen store has been practically all consumed, but secure it from
other sources.
Pavy has put forward the heterodox view that the glycogen formed
in the liver from the sugar of the portal blood is never reconverted
into sugar under normal conditions, but is changed into some other
substance or substances, and he denies that the post-mortem formation
of sugar in the hepatic tissue is a true picture of what takes place
during life. But in spite of the brilliant manner in which he has
defended this thesis, both by argument and by experiment, it must be
said that the older doctrine of Bernard, which in the main we have
followed above, is attested by such a cloud of modem witnesses that it
seems to be firmly and finally established.
Fate of the Sugar — Glycolysis. — What, now, is the fate of the
sugar which either passes right through the portal circulation from
the intestine without undergoing any change in the liver, or is
gradually produced from the hepatic glycogen ? When the pro-
portion of sugar in the blood rises above a certain low limit (about
1-5 or 2 parts per 1,000), some of it is excreted by the kidneys
(Practical Exercises, p. 716).
A large meal of carbo-hydrates is frequently followed by a
temporary glycosuria, but much depends upon the form in which
the sugar-forming material is taken. We have seen that poly-
saccharides are quite incapable of absorption as such, and that they
must be very completely hydrolysed in the lumen of the alimentary
canal before their constituent sugars have any chance of reaching the
blood. It is therefore not to be expected that the rapid absorption
of such considerable quantities of sugar as would lead to its excretion
should easily occur when the carbo-hydrate is in this form. Miura
for example, after an enormous meal of rice (equivalent to 6-4
grammes of ash- and water-free starch per kilo of body- weight),
which, as he mentions, tasked even his Japanese powers of digestion
for such food to dispose of, found not a trace of sugar in the urine.
Dextrose, cane-sugar and lactose, on the other hand, when taken in
large amount, were in part excreted by the kidneys, as was also
the case with levulose and maltose in a dog (Practical Exercises,
p. 717).* The amount of any carbo-hydrate which can be eaten
* Twenty-four healthy students, whose urine had previously been shown
to be free from sugar, ate quantities of cane-sugar varying from 250 grammes
to 750 grammes. The urine was collected in separate portions for twelve
to twenty-four hours after the meal. In only three cases was reducing sugar
found in the urine (by Fehling's and the phenyl-hydrazine test), and then
merely in traces. In eight cases cane-sugar was found, and estimated by the
polarimeter, and, after boiling with hydrochloric acid, by Fehling's solution.
METABOLISM OP CARBO-HYDRATES 54!
without the appearance of sugar in the urine is sometimes called the
assimilation limit for that carbohydrate. The attsmpt has been
made to fix the limit of tolerance of dextrose for normal persons
and persons suffering from incipient diabetes, with the object of
aiding in early diagnosis of that condition. But the limit varies with
so many conditions, only some of which can be controlled, that such
observations are not easily interpreted.
Except as an occasional phenomenon, glycosuria other than ali-
mentary is inconsistent with health; and therefore in the normal
body the sugar of the blood must be either destroyed or transformed
into some more or less permanent constituent of the tissues. The
transformation of sugar into fat we have already mentioned, and
shall have again to discuss; it only takes place under certain con-
ditions of diet, and no more than a small proportion of the sugar
which disappears from the body in twenty-four hours can ever, in
the most favourable circumstances, be converted into fat. The
dextrose which is taken up from the blood by the tissues and there
condensed to glycogen suffers sooner or later the converse change,
in all probability under the influence of diastases or glycogenases
produced in the cells, and reappears as dextrose to take its place
in the cellular katabolism and begin the series of cleavages and
oxidations by which its chemical energy is set free. Accordingly,
it is the destruction of sugar which concerns us here, and there is
every reason to believe that this takes place, not in any particular
organ, but in all active tissues, especially in the muscles, and to a
less extent in glands.
It has been asserted that the blood which leaves even a resting
muscle, or an inactive salivary gland, is poorer in sugar than that
coming to it ; and the conclusion has been drawn that in the metabo-
lism of resting muscle and gland sugar is oxidized, the carbon
passing off as carbon dioxide in the venous blood. This is indeed
extremely likely, for we know that, when the skeletal muscles of a
rabbit or guinea-pig are cut off. from the central nervous system by
curara, the production of carbon dioxide falls much below that of
an intact animal at rest ; and the carbon given off by such an animal
on its ordinary vegetable diet can be shown, by a comparison of
the chemical composition of the food and the excreta, to come
largely from carbo-hydrates. But, considering the relatively feeble
metabolism of muscles and glands when not functionally excited,
the large volume of blood which passes through them, the difficulty
of determining small differences in the proportion of sugar in such
a liquid, the possibility that even in the blood itself sugar may be
The greatest quantity of cane-sugar recovered from the urine was 8 grammes
(7.92 grammes by Fehling's method and 8-29 grammes by the polarimeter) ;
the highest proportion of the quantity taken which appeared in the urine was
2-5 per cent. When dextrose was found, cane-sugar was always present as
well.
54* METABOLISM, NUTRITION AND DIETETICS
destroyed, or that it may pass from the blood, without being oxi-
dized, into the lymph, too much weight may be easily given to the
results of direct analysis of the in-coming and out-going blood.
And although the results of Chauveau and Kaufmann, obtained in
this way, fit in fairly well with what we have already learnt by less
direct, but more trustworthy, methods, such as the study of the
respiratory exchange, they cannot be accepted as yielding exact
quantitative information. They found that in one of the muscles
of the upper lip of the horse the quantity of dextrose used up during
activity (feeding movements) was 3-5 times as much as in the same
muscle at rest, and this corresponded with the deficit of oxygen in
the blood entering the muscle, and with the excess. of carbon dioxide
in the blood leaving it. More dextrose was also destroyed in the
active than in the passive parotid gland of the horse, but the excess
per unit of weight of the organ was far less than in muscle. In dogs
whose abdominal viscera have been removed, so that they constitute
practically preparations composed of skeletal muscles it has been
found that the amount of dextrose which disappears from 100 grammes
of blood per minute varies from 0-47 to 1-8 milligrammes, the irregu-
larities probably depending largely upon the irregular consumption
by the muscles of the glycogen stored in them (Macleod and
Pearce).
Intermediary Metabolism of Carbo- Hydrates. — Concerning the pro-
cesses and the stages by which dextrose is destroyed in the tissues,
we have no very exact information, and it cannot be definitely stated
at present what share is taken by cleavage and what by oxidation,
or rather through what intermediate products, formed, it may be,
now by simple cleavage, now by oxidation, again by a combination
of cleavage and oxidation, the dextrose molecule is finally resolved
into carbon dioxide and water. It must be remembered that the
synthetic powers of animal cells are now known to be very extensive.
They build carbo-hydrates, fats, phosphatides, and proteins, as
well as destroy them, and at any of the earlier stages at any rate
the degradation products of dextrose, or some of them, may be
utilized in the construction of new compounds — for example, of fat —
either in the cells where they arise or elsewhere in the body. In
like manner the decomposition of a molecule of dextrose begun in
one cell or in one tissue may be consummated in another to which
intermediate products are conveyed in the blood. In such ways
it is obvious that the katabolic processes may be finely regulated
both qualitatively and quantitatively in accordance with the
specific wants of different organs and the intensity of their func-
tional activity from time to time. It must be said, however, that
at present there are few definitely ascertained facts to guide us in
trying to form a scheme of the actual changes which occur in the
intermediate katabolism of carbo-hydrates, and the sequence which
METABOLISM OF CARBO-HYDRATES
543
they normally follow. Glycuronic acid has been previously men-
tioned as a substance occurring even in normal urine in small
amount. It is very closely related to dextrose, as a comparison of
their constitutional formulae shows:
COOH
H— C— OH
OH— C— H
I
H— C— OH
OH
i2OH
d-dextrose.
CHaOH
rf-glyconic acid.
COOH
rf-glycuronic acid.
Glycuronic acid agrees with dextrose in containing the character-
istic aldehyde group CTT, but differs in that by oxidation two
atoms of hydrogen in the primary alcohol group CH2OH have been
replaced by one atom of oxygen. There is reason to believe that
in the tissues glycuronic acid can be formed from dextrose in the
same way, possibly through the mediation of an enzyme, and it
may therefore represent a stage in the katabolism of sugar. But
it is not known whether this is a normal transformation through
which the whole or the greater part of the dextrose passes, or only
a transformation involving a small part of the sugar under normal
conditions. The appearance in the urine of large quantities of
glycuronic acid, paired as already explained with , various com-
pounds, in certain pathological states or after the administration
of certain drugs (p. 482) , might be explained either as the result of
an increased production of that substance through a deflection of the
normal trend of carbo-hydrate degradation, or as the result of a failure
on the part of the cells to further transform the glycuronic acid in
the quantities normally produced.
Lactic acid is the one intermediate stage in the decomposition of
dextrose in the tissues whose importance seems to be definitely
ascertained. The muscles and the liver have been proved to possess
the power of producing lactic acid from dextrose obtained directly
from the blood or from the hydrolysis of their own store of glycogen,
and there is little doubt that this power is shared by many, perhaps
by all, of the other organs. There is also good evidence that the
lactic acid thus formed can be, and under normal conditions is, in
large part oxidized so as eventually to yield carbon dioxide and
water, although there is reason to believe that a portion of it may
be utilized for the synthesis of more complex bodies.
The chemistry of the change or series of changes by which lactic
add is produced from dextrose and the end-products, carbon dioxide
544
METABOLISM, NUTRITION AND DIETETICS
and water, from lactic acid has given rise to much discussion, and is
not yet clearly known. The following scheme, based on the researches
of Embden and others, and quoted from Abderhalden, illustrates one
suggestion as to the course of the series of transformations, although
it must be taken only as a diagram of the sequence of some of the
possible stages. A molecule of dextrose is represented as giving rise
to two molecules of glyceric aldehyde, each of which then yields a mole-
cule of lactic acid. Each molecule of lactic acid, losing two atoms of
hydrogen, becomes converted into a molecule of pyruvic acid, which
by the loss of the elements constituting a molecule of carbon dioxide
becomes acetaldehyde or acetic aldehyde, and this by oxidation acetic
acid, which is then oxidized to carbon dioxide and water. Thus —
SH
H— C— OH
HO— C— H
H— C— OH
H— C— OH
CH2OH
({•dextrose.
COOH
CO -CO, —
H— C— OH
CH2OH
\
H— C— OH
CH2OH
2 molecules
gjyceric aldehyde.
COOH
H— C— OH -H2
CH,
d-lactic acid.
c/-o
U
+O
CH3
Pyruvic acid.
CH3
Acetaldehyde.
COOH
Acetic acid.
2COa
-> +
2HaO
Carbon dioxide
and water.
It has been shown that acetaldehyde and carbon dioxide are formed
from pyruvic acid by the action of a ferment contained in yeast, and
there is some evidence that a similar transformation may occur in the
liver.
It is to be particularly remarked that according to this scheme
the whole of the dextrose molecule is still represented in the lactic
acid formed from it. Up to this stage no part of the molecule has
been burnt. Nearly the whole of the chemical energy — i.e., all but
about 3 per cent, of it — is still available. For a gramme of lactic
acid yields 3,661, and a gramme of dextrose 3,762, small calories on
complete combustion. The intermediate products of the decom-
position may therefore be transported from the place of origin and
utilized elsewhere with scarcely any loss of energy. Further, it is
indicated in the scheme that the degradation process is not merely
a series of cleavages and oxidations, but that these may be inter-
spersed with stages of reduction. It is also clearly suggested that
at certain points the metabolism may become recessive and syn-
METABOLISM OF CARBO-HYDRATES
545
theses be started, which may go far to retrace the steps of the pre-
ceding katabolism in respect to a portion of the dextrose.
Thus, lactic acid can be retransformed into dextrose (Mandel and
Lusk), and this, of course, into glycogen. Pyruvic acid can be
changed into lactic acid by reduction, and dextrose can in this way
be again produced. There is evidence also that under certain
conditions pyruvic acid can yield dextrose in the organism by a
different reaction, being changed into acetaldehyde, which can
then undergo transformations leading back to dextrose (Ringer).
The formation of fat from sugar may also start from some of the
stages displayed in the scheme, for it is only a short step to obtain
by the reduction of glyceric aldehyde its alcohol glycerin. And
from acetaldehyde fatty acids can be derived.
Not only does lactic acid afford a point of contact between the
metabolism of carbo-hydrates and that of fats — a junction, so to
speak, where these two great metabolic currents cross each other,
and where material originating in the one may be shunted into the
other — but it also affords a point of junction and interchange with
the current of protein metabolism. For example, the amino-acid,
alanin, yields as a decomposition product a compound called
methylglyoxal (CH3.CO.CHO), a ketonic aldehyde, which by the
assumption of a molecule of water can be changed into lactic acid.
It may also be one of the intermediate stages in the decomposition
of dextrose as a precursor of lactic acid, and one of the ways in
which the conversion of amino-acids into dextrose is accomplished
may be through this link. The presence of a ferment glyoxalase,
or probably more than one ferment which rapidly changes methyl-
glyoxal into lactic acid, has been demonstrated in tissue extracts
and in leucocytes. The same change is effected when blood con-
taining methylglyoxal is perfused through an excised surviving
liver. The reaction can be reversed for methylglyoxal like lactic
acid when given to an animal rendered diabetic by phlorhizin can be
shown to yield dextrose, possibly being first converted into glyceric
aldehyde. The conversion of methylglyoxal into lactic acid is also
a reversible reaction, for in vitro, at any rate, lactic acid readily
yields methylglyoxal (Dakin).
Pyruvic acid is another possible link. As has just been mentioned,
it probably forms a stage in the decomposition of dextrose, and has, in
addition, chemical relations on the one hand to certain of the amino-
acids, especially to alanin, and on the other to glycerin and even to
fatty acids. Thus —
H.NH2 +
COOH
Alanin (a-amino-pro-
pionic acid.
CH3
« CO 4-NHa
COOH
Pyruvic acid.
CHo.OH
*
CH
CH.OH + 2O = CO + aHJD
CH2.OH
Glycerin.
COOH
Pyruvic acid.
35
546 METABOLISM, NUTRITION AND DIETETICS
The following scheme, doubtless incomplete, illustrates a probable
chemical sequence through which the interconversion of alanin, lactic
acid, methylglyoxal and dextrose may be brought about by reactions
only involving the addition or removal of water or ammonia (Dakin) :
Dextrose
Lactic acid Zl Methylglyoxal Z± Alanin
(CH3.CHOH.COOH) (CH3.CO.CHO) (CH3.CH.NH2.COOH)
Since pyruvic acid can be reduced to lactic acid, any reaction in
which it plays a part in the intermediary metabolism of carbohydrates
or proteins can also be fitted into the scheme.
The more completely the various steps in the metabolism of the
three great groups of food substances are unveiled, the more
clearly does it appear that, far from being independent circuits,
the three currents are constantly exchanging materials with each
other.
It is to be supposed that in many of these transformations
enzymes are concerned, although comparatively little is definitely
known as to this. Normal blood itself has been credited with a
ferment which has the power of destroying sugar (glycolysis).
But with rigid aseptic precautions the loss of sugar, even in several
hours, is small, and it is doubtful whether such a ferment exists.
Even under the most favourable circumstances the quantity of
dextrose which blood can destroy is so small a fraction of that which
disappears in the same time in the body, that it is probably of no
importance in carbo-hydrate metabolism (Macleod). On the
other hand, Cohnheim stated that while no glycolytic ferment can
be demonstrated in the pancreas, and only an exceedingly weak
glycolytic action in muscular tissue (Brunton), by combining ex-
tracts of pancreas and extracts of muscles, distinct glycolysis, due
to a ferment action, could be produced. He suggested that the
glycolytic ferment is activated by another substance, as trypsinogen
is activated by enterokinase (p. 372). This announcement aroused
great interest, since it is known that the pancreas is intimately
concerned in the metabolism of sugar. That sugar disappears
under the conditions of Cohnheim's experiments has been confirmed
by a number of observers. But his interpretation of his results has
not been generally accepted. According to Levene and Meyer,
the dextrose, far from being burnt, seems to be condensed to a poly-
saccharide, and can be recovered by hydrolysing this compound
when the mixture is acted on by dilute acid. The action of the
pancreas- muscle mixture is, therefore, not a true glycolysis. In-
deed, of all the tissues investigated by Levene, leucocytes alone can
be credited with a real glycolytic action. Excision of the pancreas
in dogs causes permanent glycosuria (pancreatic diabetes) (v. Mering
and Minkowski), which is prevented if a portion of the pancreas be
METABOLISM OF CARBO-HYDRATES— GLYCOSURI AS 547
left (p. 636). Diabetes in man is known to be frequently associated
with pancreatic lesions. Although much still remains obscure, the
study of this pathological form of glycosuria and of the experimental
glycosurias has thrown light upon the normal metabolism of carbo-
hydrates and upon those regulative mechanisms whose breakdown
is responsible for the excretion of sugar. It will be best to discuss
the experimental glycosurias first, and to begin with the form which
probably is better understood than any other, the so-called punc-
ture glycosuria.
Puncture Glycosuria — Sugar-Regulating Mechanism. — An arti-
ficial and temporary glycosuria, in which the sugar in the urine un-
doubtedly arises from the hepatic glycogen, can be caused by punc-
turing the medulla oblongata in a rabbit — for example, at a level
between the origins of the auditory nerves and the vagi. It is stated
that a puncture of the thalamencephalon, or 'tween-brain (p. 850),
produces the same effect. If the animal has been previously fed with
a diet rich in carbo-hydrates — that is, if it has been put under con-
ditions in which the liver contains much glycogen — the quantity of
sugar excreted by the kidneys will be large. The immediate cause
of the glycosuria is an increase in the sugar content of the blood
(hyperglycaemia), an increase which is most pronounced in the blood
of the hepatic vein. If, on the other hand, the animal has been
starved before the operation, so that the liver is free, or almost free,
from glycogen, the puncture will cause little or no sugar to appear
in the urine, and the proportion of sugar in the blood will remain
normal. That nervous influences are in some way involved in the
mobilization of the glycogen reserve of the liver is shown by the
absence of glycosuria if the splanchnic nerves, or the spinal cord
above the third or fourth dorsal vertebra, be cut before the puncture
is made. But sometimes these operations are themselves followed
by temporary glycosuria, due, it is believed, to irritation of the
same efferent nervous path whose elimination when the splanchnics
are divided prevents the glycosuria. The simplest explanation of
the phenomena is that a ' sugar centre ' — that is to say, a centre
which has the important office of regulating the sugar content of the
blood by governing the rate at which glycogen is built up and de-
composed in the liver, as the salivary centre regulates the rate at
which the constituents of saliva are formed and discharged— has
been injured or irritated by the puncture. If a nervous centre does
in fact preside over this internal secretion of the liver, it will, of
course, be connected with efferent and afferent nerves. The former,
as defined by the experiments alluded to, seem to be confined to
the splanchnic nerves; the latter are believed to run especially,
though not exclusively, in the vagus. Section of the vagi has no
effect either in causing glycosuria of itself or in preventing the
' puncture ' glycosuria, but stimulation of the central ends of these
548 METABOLISM, NUTRITION AND DIETETICS
and of other afferent nerves may cause sugar to appear in the
urine, although not, it is said, if precautions are taken to prevent
any degree of asphyxia. Asphyxia produces an increase in the
sugar content of the blood, an increase in the flow of urine and
glycosuria.
It has usually been assumed that this action of asphyxia is due to
the effect upon the centre of blood over-rich in carbon dioxide (and
other metabolic products) or impoverished as regards oxygen. But
there is some evidence that the altered blood may also affect the
liver-cells directly, or, what comes to the same thing in the long-run,
that interference with the internal respiration of the hepatic tissue,
operating, it may be, through an increase in the concentration of the
hydrogen ions, upsets the equilibrium of those intracellular reactions
by which glycogen is formed from dextrose and dextrose from
glycogen. In like manner it may be supposed that under normal
conditions the rate of transformation of the hepatic glycogen into
dextrose is adjusted to the dextrose content of the blood, not only
by reflex nervous impulses passing through the sugar-regulating
centre, but also by the direct influence of the dextrose itself circu-
lating in the blood, upon whose concentration the reaction of the
centre on the one hand and of the liver-cells on the other may in
part depend. So that when the proportion of sugar in the blood
tends to sink we may perhaps picture the centre as sending impulses
to the liver which increase the rate at which the glycogen is hydro-
lysed ; and when the proportion tends to rise, we may think of it as
sending impulses which inhibit the hydrolysis, both effects being
accentuated by the direct influence of the changes of concen-
tration on the hepatic cells. Whatever the mechanism may be
through which the puncture hastens the transformation of glycogen
into dextrose in the liver, there is no evidence that the amount of the
enzyme which hydrolyses the glycpgen is increased. Whether the
action of the enzyme is favoured in some other way — e.g., by the
production of a co-ferment or by some change in the condition of
the glycogen which renders it more open to attack — is unknown.
Certain facts have recently been brought forward which go to
show that the action of the splanchnic fibres on the liver is not
a direct action, but that in some way or other the concomitant
activity of the adrenal glands is essential. For if the adrenals have
been previously extirpated, the puncture does not cause glycosuria.
It was at first thought that the reason for this was that the removal
of - the adrenals is itself followed by the disappearance of glycogen
from the liver, and, as has been pointed out, the presence of glycogen
in the liver is essential to the success of the puncture experiment.
The matter, however, is not so simple. For although in certain
animals — e.g., the dog — the liver does lose all its glycogen when the
adrenals have been taken away, this is not the case in the rabbit,
METABOLISM OF CARBO-HYDRATES— GLYCOSURI AS 549
and yet in the rabbit also the urine remains free from sugar after
puncture in the absence of the adrenal glands. In some way or
other, then, the adrenals do intervene in the production of puncture
glycosuria. The observation, which is easily confirmed, that the
injection of adrenalin (or epinephrin) (p. 550) under the skin or into
the blood, or into one of the serous sacs, does cause a pronounced
increase in the sugar content of the blood, and the appearance of
dextrose in the urine, seemed at first to supply the missing link in
the chain of evidence. What could be simpler than the assumpt:, n
that the splanchnic fibres stimulated in the puncture experiment
were fibres going not to the liver, but to the adrenals, which occa-'
sioned an outpouring of adrenalin into the blood^and that puncture
glycosuria was therefore merely a particular case"of adrenalin glyco-
suria ? It is known that excitation of the splanchnic nerves cauces
the passage of adrenalin into the blood of the adrenal veins (p. 661).
It is known that puncture of the medulla oblongata diminishes the
epinephrin content of the adrenal glands. The argument seemed
straightforward, and the adrenal hypothesis of puncture glycosr.ria
triumphant. As soon, however, as the matter was put to the test
of quantitative experiments, the hypothesis began to crumble. It
was shown, for example, that during a stimulation of the splanchnic
nerves sufficient to cause a decided increase in the dextrose content
of the blood, a quantity of adrenalin was given off. to the Adrenal
veins, which, when mingled with the rest of the blood on its way
to the liver, could not possibly amount to more than one in a hundred
million parts of blood, a concentration in which adrenalin, when
introduced artificially into the blood-stream, produces no glycosuna
whatever. Still more significant is the fact that, after destroying the
hepatic plexus, stimulation of the splanchnic nerves causes no in-
crease in the blood-sugar in spite of the increased output of adrenalin
by the way of the adrenal veins. On the other hand, excitation
of the hepatic plexus causes hyperglycsemia (Macleod and Pearce).
It is not, then, a direct action on the liver of epinephrin secreted in
response to stimulation of splanchnic fibres supplying the adrenal
glands which is responsible for the increase in the dextrose content
of the blood. The adrenals, however, play some part. For in their
absence stimulation of the hepatic plexus is not followed by hyper-
glycaemia. But whether this is due to general derangement of the
normal carbo-hydrate metabolism in their absence, or to the loss of .
some special influence on the liver, without which stimulation of the
hepatic plexus is ineffective, is unknown.
Although several of the operations which lead to temporary
glycosuria undoubtedly bring about changes in the hepatic circula-
tion, it is as yet impossible to say whether vaso-motor effects con-
tribute essentially to the result, or whether it is due entirely to
nervous stimulation of the liver-cells, or to withdrawal of such
550 METABOLISM, NUTRITION AND DIETETICS
stimulation or control (see also p. 509). There is some evidence
that excitation of the uncut great splanchnic nerve (on the left side)
in dogs may cause hyperglycsemia, diuresis, and glycosuria, even
under conditions in which as far as possible circulatory effects are
eliminated. Contrariwise, when in the puncture experiment on an
unnarcotized animal the small instrument does not wound the
medulla oblongata in the right place, a rise of blood-pressure due
to excitation of the vaso-motor centre may occur without any
glycosuria. But absolute proof of the existence of glycogenolytic
nerve fibres going to the liver — that is, fibres whose stimulation
accelerates the hydrolysis of glycogen into dextrose (Macleod) — has
not yet been brought forward.
Adrenalin Glycosuria.— In adrenalin glycosuria the sugar-content
of the blood is increased. A given quantity of adrenalin introduced
subcutaneously produces a more marked hyperglycaemia and
glycosuria than the same amount injected into a vein or into muscle.
The best evidence is that the glycosuria is produced by some action
on the liver, possibly through the excitation of sympathetic fibres
controlling the production of dextrose from glycogen (Underbill and
Closson), or by a direct effect on the hepatic cells, which hastens the
normal transformation of glycogen into dextrose, or hinders the
normal transformation of dextrose into glycogen. It has been
stated that in the isolated surviving liver of the frog adrenalin causes
the glycogen to be rapidly converted into dextrose. While this
confirms the view that experimental adrenalin glycosuria is due to
an action on the liver which increases the sugar-content of the blood,
it does not necessarily show that the action is exerted directly on
the hepatic cells without the intervention of nerve fibres. For the
sympathetic nerve-endings may survive a considerable time. The
theory that epinephrin causes glycosuria by inhibiting the internal
secretion of the. pancreas, and that the condition is therefore a par-
ticular variety of pancreatic diabetes, is erroneous. Adrenalin
glycosuria does not seem to be in any way related to true
diabetes. The complete metabolism of dextrose is not interfered
with. Indeed, a much larger proportion of the total heat produced
comes from the destruction of sugar after the subcutaneous injection
of epinephrin into dogs than in the normal animals (Lusk and Riche).
If in spite of this glycosuria ensues, it is only because the carbo-
hydrate reserve of the body is mobilized so rapidly that it cannot
possibly be all consumed. Nor does epinephrin cause any increased
production of sugar from protein or from fat. For in dogs rendered
diabetic by phlorhizin and freed from glycogen by shivering, injec-
tion of epinephrin is not followed by an' increase of either sugar or
nitrogen in the urine (Ringer). After repeated injections of adren-
alin, a tolerance for it is established, and glycosuria is no longer
caused.
METABOLISM OF CARBO-HYDRATES-GLYCOSURIAS 551
Fhlorhizin Glycosuria, produced by subcutaneous injection of the
glucoside phlorhizin, agrees with pancreatic, but differs from punc-
ture diabetes in this, that it can be produced in an animal free
from glycogen, and is accompanied by extensive destruction of
proteins. It differs from other forms of diabetes in being associated,
not with an increase, but with a diminution, in the sugar of the blood.
This is best explained by supposing that the phlorhizin acts on the
kidney in such a way as to increase the permeability of the glomeru-
lar epithelium for sugar, or (in terms of the secretion theory of urine
formation) in such a way as to increase its sensitiveness to the
stimulus of sugar circulating in the blood. The sugar is therefore
rapidly swept out of the circulation, and this leads secondarily to
an increased production of sugar to make good the loss. In addi-
tion, within certain limits there is a total inability on the part of
the body to consume dextrose.
After the preliminary sweeping out of the sugar already in the
body, a definite ratio is established between the dextrose and the
nitrogen eliminated in the urine (dextrose : nitrogen : : 3~6or 37 : i).
The sugar at this stage is produced entirely from proteins, and not
at all from fat. It is a fact of considerable interest that, if small
quantities of dextrose are now given, the amount of protein de-
stroyed is reduced to some extent, although all of the dextrose is
excreted, and none of it is burnt (Ringer). This supports the
hypothesis of Landergren that in starvation some of the protein is
metabolized for the formation of the indispensable dextrose, and
that this fraction can be ' spared ' by carbohydrate, though not by
fat. The protein metabolized is so much increased under the
influence of phlorhizin that it exceeds the starvation requirement
by a greater amount than in pancreatic diabetes, perhaps because
the diminished content of sugar in the blood constitutes a more
insistent call upon the proteins to produce sugar. In pancreatic
diabetes, where hyper glycsemia exists, there can at least be no
reason for the formation of sugar from protein for the maintenance
of the normal sugar-content of the blood, and it is interesting that
in this condition the giving of dextrose does not seem to spare any
protein (p. 606). The degree of intolerance for carbo-hydrates in
pathological diabetes may be arrived at by putting the patient on
a diet of protein and fat (rich cream, meat, butter, and eggs), and
determining the ratio of dextrose to nitrogen excreted. If it as
3-6 or 3-7: i, intolerance is complete, none of the dextrose produced
from protein being burned (Lusk and Mandel).
Glycosuria can be caused in many other ways than those already
mentioned. Sometimes the action seems to be a direct one on the
sugar-regulating centre — e.g., in concussion of the brain, occlusion
and subsequent release of the arteries supplying the brain and
cervical cord, and acute haemorrhage. Carbon monoxide has a
552 METABOLISM, NUTRITION AND DIETETICS
similar action owing to the deficiency of oxygen occasioned by it.
Many drugs also cause glycosuria, including curara, morphine,
strychnine, phosphorus, chloroform, ether, and other substances,
some of which may act on the ' sugar centre,' although others — e.g.,
phosphorus and chloroform— are poisons which can affect the liver
directly. It is probable that some of the experimental hyper-
glycaemias are due to an associated acidosis. For when the hydrogen-
ion concentration of the blood is increased the transformation of
glycogen into dextrose in the liver is accelerated. The adminis-
tration of alkali is said to have a beneficial influence upon the
oxidation of dextrose in dogs after total or partial extirpation of the
pancreas (Murlin and Kramer). Injection of water or physiological
salt solution into the bile-ducts, or into the mesenteric veins, or of
salt solution in considerable amount into the general circulation,
is followed by glycosuria (Fischer, etc.). It is a mistake to apply
the term diabetes to most of the forms of artificial hyperglycaemia
and glycosuria. The condition produced by removal of the pan-
creas, which will be returned to in Chapter XI., is, however, a true
diabetes, a derangement of metabolism of the sam° general nature
as that which underlies human diabetes.
Diabetes Mellitus. — In the natural diabetes of man, as in all
the forms of glycosuria mentioned, with the exception of that pro-
duced by phlorhizin, the immediate cause of the glycosuria is the in-
crease of sugar in the blood. Instead of the i part per 1,000, or a
little more or less, which constitutes the normal proportion in a
healthy man, in diabetes 3 or 4 parts, and in exceptional cases even 7
to 10 parts per 1,000 may be present. The riddle of diabetes is the
explanation of this persistent hyperglycaemia. Innumerable hypo-
theses have been framed to account for this, but on the whole
three possibilities have been emphasized: (i) That the power of
temporarily storing carbohydrates is deranged; (2) that the power
of the tissues to utilize carbo-hydrates (i.e., eventually dextrose)
is diminished or abolished ; (3) that too much sugar is produced in
the body. In addition, some writers have postulated a fourth
factor to explain certain cases (of so-called ' renal diabetes ') — to wit,
an increase in the permeability of the kidneys for sugar, as in
phlorhizin glycosuria. Lest the student should be bewildered
amongst all these theories, he should take note that while the second
factor is now recognized as the essential one, there is some reason
to believe that diabetes mellitus is not in every case a single patho-
logical condition, but may comprise a group of such conditions.
Some cases may therefore present a picture conforming closely to
one or to another of the experimental glycosurias, but others a
picture compounded of features characteristic of two or of several
of these experimental conditions.
METABOLISM OF CARBO-HYDRATES— GLYCOSURI AS 553
It is possible that in some cases the sugar coming from the ali-
mentary canal passes entirely or in too large amount through the
liver, owing to a deficiency in its power of forming glycogen. But
although in certain cases of diabetes specimens of the hepatic cells,
obtained by plunging a trocar into the liver, have been found free,
from glycogen, in others glycogen has been present. The muscles
also are usually stated to be much poorer in glycogen than normal
muscles, but this might just as well be the case because glycogen
was being transformed into sugar with abnormal ease as because
there was interference with glycogen formation. Indeed, it is said
that in the heart muscle of depancreatized dogs there is more glycc-
gen than in normal heart muscle. It must be carefully remembered
that the amount of glycogen present in a tissue gives no information
as to the rate at which it is being formed or decomposed. And if
the cause of the supposed defect in glycogen-forming power be the
absence of a glycogen-forming ferment, or its production in too small
an amount, the same circumstance may occasion a too tardy
transformation into sugar of whatever glycogen happens to be
present. In this case the sugar-regulating function of the glyco-
gen store would be equally lost, whether the storehouses were
permanently filled with long-formed glycogen or only half-filled or
empty.
In addition to an interference with the due and regulated storage
of the surplus sugar as glycogen, it has usually been thought neces-
sary for a rational explanation of the facts of diabetes, to assume
that from some change in the tissues sugar has ceased to be a food
for them, or is used up in smaller amount than in the healthy body.
More and more the evidence points to this as the fundamental
change both in the human disease and in experimental pancreatic
diabetes.
Why the tissues cannot decompose and utilize dextrose as they
normally do, if it be really the case that they fail in this regard, is a
question of great interest, but as yet no satisfactory answer can
be given. It appears probable that the failure occurs at one or more
of the earliest stages in the intermediate metabolism of carbo-
hydrates (p. 542) or in the preliminary processes, whatever they
may be, which, without profoundly altering the dextrose molecule,
prepare it for the series of decompositions, in the course of which it
eventually parts with all iis chemical energy. For it has been
shown that many of the products of the cleavage or oxidation of
sugar, even those in which the decomposition has proceeded but a
little way — e.g., glyconic and glycuronic acids (p. 543) — are com-
pletely utilized by the tissues of diabetics and of depancreatized
dogs. And the derangement in the normal sequence of events, of
whatever nature it may be, is not so deep-reaching as to prevent
554 METABOLISM, NUTRITION AND DIETETICS
the retracing of the chemical steps by which sugar is synthesized
from such derivatives of the proteins as amino-acids or their further
degradation products. As to the actual cause of the alleged in-
capacity of the tissues to consume dextrose, the change has by some
been supposed to be the loss or diminution of a glycolytic ferment
or a substance necessary for the activation of such a ferment. And
although the sugar-destroying power of blood from diabetic patients,
or from animals in which glycosuria has been caused by phlorhizin,
is not at all inferior to that of healthy blood, it has been maintained
that the intracellular glycolytic ferments, if such really exist, are
much less active, especially in the more severe forms of the disease,
which conform so closely in their clinical manifestations to the pic-
ture presented by the depancreatized animal. Nevertheless, up to
the present ah1 attempts to satisfactorily demonstrate for isolated
tissues a loss or even a diminution in the capacity to utilize dextrose
have broken down. In eviscerated dogs, for example — that is, in
preparations consisting mainly of skeletal muscle — it has been found
impossible to make out any deficiency as compared with normal
animals in the amount of dextrose disappearing in a given time
from the blood, even when the animals have been deprived of the
pancreas as long as a week before the experiment, and therefore
exhibit the condition of pancreatic diabetes in full intensity
(Macleod and Pearce). This conclusion has been confirmed for the
isolated heart -lung preparation.
As regards the hypothesis that an increased production of sugar
from proteins, or it may be from fat, is the essential proximate cause
of the hyperglycaemia and the glycosuria, there is no good evidence
that this factor, acting by itself in the absence of a derangement of
the regulative influence of the glycogen store, and in the absence of
a derangement of the normal katabolism of dextrose, is ever respon-
sible for pathological diabetes. But a secondary overproduction
of sugar unquestionably occurs in many cases. The tissues, bathed
as they are in liquids rich in dextrose, are nevertheless starving for
sugary if they cannot use what is offered to them, and the body
labours to avert the famine by increasing its production of sugar,
the sugar- forming tissues being stimulated to their task either
through nervous influences or by chemical messengers circulating
in the blood.
In depancreatized dogs, and in dogs under the influence
of phlorhizin, glycerin, given by the mouth, causes an increase in
the excretion of sugar up to two or three times the original amount.
The giving of fat does not increase the amount of sugar excreted,
which, however, is increased by such substances as egg-yolk, which
contain lecithin. These should accordingly be avoided in cases in
which a strictly antidiabetic diet is desired. It is much more im-
portant to exclude carbo-hydrates largely or entirely from the food,
METABOLISM OF CARBO-HYDRATES— GLYCOSURI AS 555
although oatmeal and potatoes are said to occupy an exceptional
position, and have even been recommended as beneficial. Calcium
chloride has been stated to diminish the sugar excretion in diabetes
(Boigey), and it has a similar effect in certain of the artificial glyco-
surias (Brown, Fischer).
In many cases, even when carbo-hydrates are completely, or
almost completely, omitted from the food, sugar, derived from the
breaking-down of proteins, and possibly to some extent from fats,
still continues to be excreted, although in smaller quantity. Other
products formed or imperfectly transformed in the deranged meta-
bolism, especially of fats, such as acetone, aceto-acetic acid, and
oxybutyric acid (the so-called acetone bodies), may also appear in the
urine (ketonuria), or, accumulating in the blood, may, by uniting with
its alkalies, seriously diminish the quantity of carbon dioxide which
that liquid is capable of carrying, and thus lead to the condition
known as diabetic coma. The small amount of carbon dioxide in
the venous blood may also be partly due to the hyperpnoea, marked
by increased depth of the respiratory movements produced by
stimulation of the respiratory centre by other substances than carbon
dioxide. The increased ventilation causes a fall in the carbon
dioxide pressure in the alveolar air, and therefore an increased
elimination of that gas from the blood. This form of coma appears
to be really in part an acid-poisoning comparable to the condition
produced in animals by doses of mineral acids too large to be
neutralized by the ammonia split off from the proteins. The ad-
ministration of very large doses of alkalies (sodium bicarbonate,
for instance, to the amount even of hundreds of grammes) has
been recommended for the treatment of this serious complication,
and in some cases i.t is successful in staving it off for a time. Often,
however, in spite of a prolonged course of treatment, during which
the urine has continued distinctly alkaline, fatal coma eventually
occurs. The coma then is not merely a symptom of acidosis,
but is also due to the specific toxic effects of the acids even when
neutralized. Other toxic products may also be formed in the
deranged metabolism. The appearance of the acetone bodies in
diabetes presents a problem which cannot be said to have been as
yet completely solved. Oxybutyric acid, from which aceto-acetic
acid and acetone are easily derived (p. 567), seems to be one of the
intermediate steps in the normal metabolism of fats. But whereas
under ordinary circumstances it is readily oxidized in the body, in
diabetes the power of the tissues to burn oxybutyric acid seems to
suffer just as does the power to utilize dextrose. The suggestion
that in diabetes the abnormally great consumption of fat entailed by
the loss of availability on the part of the carbo-hydrates causes the
intermediary metabolism of fats to be scamped, as it were, is not
satisfactory. For many animals and some races of men dwelling
5j6 METABOLISM, NUTRITION AND DIETETICS
in cold climates consume with impunity much greater quantities
of fat than any diabetic organism.*
N II. — THE METABOLISM OF FAT.
Chemistry of Fats. — The fats are compounds (esters) of an alcohol
with fatty acids, and can be split, with assumption of water, into these
constituents by the action of acids or alkalies or of enzymes (lipases).
In the majority of the ordinary fats, and in all those which are of
physiological importance (the triglyce rides), the alcohol is glycerin.
The fatty acid components which may be united with the glycerin are
very numerous, and the physical properties of the different fats — e.g.,
their melting-points and solubilities — are closely related to the physical
properties of the corresponding fatty acids. Thus palmitic and
stearic acids are solid at ordinary temperatures, and so are palmitin
and stearin, the glycerin esters or fats formed with these acids. Olcic
acid, on the contrary, is fluid at the ordinary temperature, and the
corresponding fat, olein, is a liquid fat or oil. On the chemical side
the fatty acids can be distinguished as saturated and unsaturated.
The fatty acids of the series CnH^+x-COOH are saturated acids.
Where n is o we have formic acid, H.COOH; where n is i, acetic acid,
CH3.COOH; where n is 2, propionic acid, CH3.CHa.COOH ; where
n is 3, butyric acid, CH3.CH2.CHa.COOH, and so on, each acid in the
series differing from the one immediately preceding it in possessing an
additional CHa group. In the case of the higher members of the series
these carbon chains become very long. In palmitic acid, for instance,
CHS.(CH2)14.COOH, there are fourteen CHa groups, and in stearic acid,
CHs.tCH^.COOH, sixteen. Oleic acid,C8217"X=C/™ . COOH
is a representative of a series of unsaturated fatty acids whose general
formula is CnH^-i-COOH. As the formula of oleic acid shows, the
unsaturated fatty acids contain hi their molecule two carbon atoms
united by a double link, and one of these valencies can be occupied by
halogens (e.g., chlorine) or by oxygen. Erucic acid, a fatty acid occur-
ring in certain vegetable oils — for example, in rape oil — also belongs to
this series, and linolic acid, found in linseed oil, to another series of
unsaturated fatty acids. Then there are the so-called oxyfatty acids,
which in their turn comprise saturated and unsaturated acids. They
differ from the ordinary fatty acids in containing one or more OH
groups. Thus a dioxystearic acid, C17H33(OH)2.COOH, in which two
of the H atoms in stearic acid are replaced by OH, is found in castor-oil.
It is clear, from the great variety of the fatty acids, that by their union
with glycerin (with loss of water) a very large number of different fats
can be formed . Thus, when all the OH groups in the trivalent alcohol are
replaced by palmitic acid we have tripalmitin ; when they are replaced
by stearic acid, tristearin ; when they are replaced by oleic acid, triolein ;
and so on. As a group such fats may be termed homo-acid fats, since all
the OH groups are replaced by the same fatty acid. Thus —
CHj.OH C^H^.COOH
CH.OH + CH
CHj.OH C^H
Glycerin. 3 molecules stearic acid. Tristearin. \Vatet.
* The importance of controlling the diet, even to the extent of introducing
periods of fasting, so as to keep the diabetic free from acidosis and glycosuria,
has been recently emphasised (Allen) .
THE METABOLISM OF FAT 557
But it is not necessary that each OH group in the alcohol should be
replaced by the same fatty acid, and when this does not occur we have
hetero-acid fats. For instance, one can be replaced by steeiric acid,
and the remaining two by palmitic acid, yielding a fat called ' stearo-
dipalmitin.' Conversely, one OH may be replaced by palmitic and two
by stearic acid, forming palmito-distearin. Similarly, a dioleo-stearin
(glycerin combined with two molecules of oleic and one of stearic acid),
and an oleo-distearin (glycerin combined with two molecules of stearic
and one of oleic acid) are known. Such compounds have been isolated
from the fat of animals, and also formed synthetically. Again, each
of the OH groups in the alcohol can be replaced by a different fatty acid.
It is obvious, then — and this is the point to which these chemical
details are intended to lead up — that the number of different fats
which the animal organism has at its disposal for concocting those
varied mixtures designated as body fat is very great, and that there
is room for a considerable degree of specificity in the fat stores of
different animals, and it may be in the fat contained in different
organs of the same animal, even if this specificity is not as marked
as in the case of the proteins. It may be added, in connection with
the composition of the body fat, that small quantities of free fatty
acids and of glycerin may be present ; but there is reason to believe
that these are simply the surplus of raw materials which is about to
be synthetized to neutral fat, or the surplus of decomposition
products of the neutral fat which have not yet left the fat depots
to take their place in the metabolism of the tissues.
The discussion of the metabolism of fat involves a study — (i) of
the transformations and migrations of the food fat before it begins
to be utilized ; (2) of the possible production of fat from other con-
stituents of the food ; (3) of the processes and the stages by which
fat, whatever its origin, undergoes katabolism to its end products.
The fat of the food, passing along the thoracic duct into the blood-
stream, is soon removed from the circulation, for normal blood
contains only traces, except during digestion. Where does it go ?
What is its fate ?
Transformation and Migration of the Food Fat. — The presence
of adipose tissue in the body might suggest a ready answer
to these questions. The fat-cells of adipose tissue are ordinary
fixed connective-tissue cells which have become filled with fat,
the protoplasm being reduced to a narrow ring, in which the
nucleus is set like a stone. It would, at first thought, seem natural
to suppose that the fat of the food is rapidly separated by these
cells from the blood, and slowly given up again as the needs of 'the
organism require, just as carbo-hydrate is stored in the liver for
gradual use. And it has been found that a lean dog, fed with a
diet containing much fat and little protein, puts on more fat, as
estimated by direct analysis, or keeps back more carbon, as esti-
mated by measurements of the respiratory exchange, than can be
accounted for on the supposition that even the whole of the carbon
of the broken-down protein corresponding to the excreted nitrogen
558 METABOLISM. NUTRITION AND DIETETICS
has been laid up in the form of fat. Even with a diet of pure fat — •
and with such a diet digestion and absorption are carried on under
unfavourable conditions — more carbon is retained than can have
come from the metabolism of the proteins of the body, as measured
by the nitrogen given off in the urine and faeces: the fat passes
rapidly from the blood into the organs, and especially into the liver
(Hofmann, Pettenkofer and Voit). It is thus certain that some of
the absorbed fat may be stored up as fat in the body.
This is borne out by the careful experiments of Munk and Lebe-
deff, who found that, when dogs are fed with excess of foreign fat
(linseed oil, rape oil, mutton fat), a fat is laid down which is quite
different from dog's fat, and has the greatest resemblance to the fat
of the food. Thus, when rape oil, which contains a fatty acid,
erucic acid, not found in animal fat, was given, erucic acid could be
detected in the fat laid on. When the dogs were fed with mutton
fat, whose melting-point is much higher than that of dog's fat, the
fat laid on did not melt till it was heated to 40° C. or more. When
they were fed with linseed oil, the body-fat was found liquid even
at o° C. We have already referred (p. 444) to the fact that neutral
fat can be built up in the wall of the intestine from fatty acids given
in the food. Munk has shown that fat formed in this way can also
be laid down as body-fat. But besides the fat and fatty acids of
the food, the fat of the body has other sources, and some of it is
produced by more complex processes.
The fat of a dog consists of a mixture of palmitin, olein, and
stearin. When a starved dog was fed on lean meat and a fat con-
taining palmitin and olein, but no stearin, the fat put on contained
all three, and did not sensibly differ in its composition from the
normal fat of the dog (Subbotin). Stearin must, therefore, have
been formed in some way or other in the body. If it was produced
from the olein and palmitin of the food, the portion of these deposited
in the cells of the adipose tissue must have undergone changes before
reaching this comparatively fixed position. But there is conclusive
evidence that fat may be derived from other sources, certainly
from carbo-hydrates, and probably from proteins; and the stearin
may have been formed from the carbo-hydrates or proteins of the
food or tissues, and not directly from fat. And if the stearin was
produced from proteins or carbo-hydrates, it is evident that the
olein and palmitin might have been formed in this way too, the
portion of the carbo-hydrate or protein devoted to this purpose
being sheltered from oxidation by the combustion of the fats of the
food. It is well known that not only neutral fats, but also fatty
acids, exert such a ' protein-sparing ' action. It is possible also that
the fat which is normally excreted into the intestine (p. 443), and
which is perhaps derived from broken-down proteins, may be re-
absorbed, and take its place among the fat ' put on.'
THE METABOLISM OF FAT 559
At this point in the discussion it is necessary to remark that a
distinction ought to be established between that store of surplus fat
laid down in the connective tissue which, in order to avoid com-
plicating the matter unduly, has hitherto been referred to as if it
constituted the whole of the body-fat, and the fat which is contained
in greater or less amount in all the tissue cells. The fat con-
tained in the tissue elements — e.g., in the liver cells — in the visible
form of droplets, and which can be easily extracted from them by
solvents such as chloroform, should also be distinguished from the
fat which is so intimately incorporated or combined with the cell
substance that it can only be extracted after this has been digested
by the aid of proteolytic ferments or acids. The latter fraction of
the body-fat is probably an integral and indispensable constituent
of the protoplasm. Now, it is in the great fat depots of the sub-
cutaneous tissue and the mesentery and omentum that variations
in the proportions of the various fatty acids corresponding to varia-
tions in the nature of the food-fat are most easily produced, or, at
least, most easily observed. These depots are laid down, not in
the interest of the fat cells themselves, but to serve the purpose of
a reserve of fat which may be drawn upon for the nutrition of the
body as a whole, just as the glycogen store of the liver forms a
general carbo-hydrate reserve. The free fat in the cells of the organs
is superficially analogous to the glycogen reserves of such tissues
as muscles and glands, and certain facts are known which might
be interpreted as indicating that this fraction of the body-fat, like
the fat of the connective tissue, is not a definite and specific mixture
of fats with an unvarying composition for each kind of animal, but
a mixture whose composition can be made to vary by altering the
nature of the fats in the food. On the other hand, the fat combined
in the tissues appears to preserve a certain specificity which is inde-
pendent of the fats supplied in the food. Thus, wh'en dogs were
fed with rape oil, and had accumulated considerable quantities of
this fat of low melting-point in the subcutaneous and other fat
depots, \ he fat combined in the organs remained in all respects the
same as normal dog's fat. This was also the case with animals
fed on fat of high melting-point, such as sheep's tallow (Abderhalden).
Although the liver appears to have a special relation to the metabo-
lism of fat, it is not known whether any particular organ is more
than the rest responsible for the manufacture of this specific mix-
ture of fats. It appears more probable that each cell has the power
of forming for itself the characteristic fats from the crude materials
represented by the food-fat directly absorbed from the tissue lymph,
or the fat of the depots after it has been mobilized and has found
its way again into the blood, or, finally, from other materials than
fats, such as dextrose or some of its decomposition products.
Even in the case of the subcutaneous and similar collections of
560 METABOLISM. NUTRITION AND DIETETICS
fat, it must be noted that upon the whole, under normal conditions,
it is their specificity of composition rather than their dependence
upon the composition of the fat mixture in the food which is the
striking fact, and undue weight can easily be given to the results
of feeding experiments where great quantities of quite foreign fats
are administered. When small quantities of fats very far removed
in their properties from the normal fat of an animal are given
in the food, they are either completely utilized before reaching
the fat depots, or transformed into normal body- fat, since no change
whatever can be detected in the latter. If they have been utilized,
then it may be that a corresponding amount of fat, formed, say,
from dextrose, has been laid down in the fat stores. If this fat is
formed from dextrose, it will, of course, be the kind of fat which
the particular animal is accustomed to form from dextrose — that
is, the fat characteristic of the animal. If the foreign fat is itself
transformed into body-fat when given in small amount, this same
feat can without doubt be gradually accomplished in the case of
the surplus of foreign fat laid down in the depots when a large
quantity of it is given in the food.
Formation of Fat from Other Sources than the Fat of the Food —
(i) From Carbo- Hydrates. — It has been found that the addition of
protein to a diet of fat, and especially to a diet of carbo-hydrate,
in larger amount than is just necessary for nitrogenous equilibrium
(p. 602), leads to a more rapid increase in the carbon deficit — that
is, in the fat put on — than if the minimum quantity of protein
required for nitrogenous equilibrium had been given. From this it is
inferred that the carbonaceous residue of the broken-down protein is
shielded from oxidation by the fat, and to a still greater extent by
the carbo-hydrates, and so retained in the body as fat. And there
is little doubt that the high repute of carbo-hydrates as fattening
agents is in part due to their taking the place of proteins and fats
in ordinary ' current ' metabolism, and so allowing body-fat to be
laid down from these. Voit, indeed, has gone so far as to assert
that this is the only sense in which carbo-hydrates can be said to
form fat, and that, in carnivorous animals at least, a direct con-
version never occurs. But the experiments of Rubner have shown
that in a dog fed with a diet rich in carbo-hydrates, and containing
but little fat and no proteins at all, the carbon deficit was greater
than could be accounted for by the proteins being broken down in
the body and the fat of the food. In the pig and goose, too, the
direct formation of fat from carbo-hydrates has been demonstrated.
For example, in an experiment by Tscherwinsky two young pigs
of the same litter were taken. They weighed respectively 7,300 grammes
and 7,290 grammes. One was killed, and the amount of fat and nitrogen
in its body directly estimated. From the nitrogen the maximum
quantity of protein which could be present was calculated. The other
pig was fed for four months with barley, which was analyzed. The
excreta were also analyzed to determine the amount of unabsorbed
THE METABOLISM OF FAT 56*
fat and protein. At the end of the iour months the pig was killed.
It now weighed 24 kilogrammes, and contained 2-52 kilogrammes
protein and 9-25 kilogrammes fat. Subtracting the protein (0-96 kilo-
gramme) and fat (0-69 kilogramme) originally present, 1-56 kilogrammes
of protein and 8-56 kilogrammes of fat must have been put on. The
amount of protein taken in the food was 7-49 kilogrammes, and of fat
0-66 kilogramme. Therefore, 5-93 kilogrammes of protein must have
been used up, and 7-90 kilogrammes of fat laid on. At least 5 kilo-
grammes of this fat must have come from the carbo-hydrate of the
food. Only a small amount of the fat put on could possibly have come
from the protein.
The production of wax by bees, which used to be given as a proof
of the formation of fat from sugar, is not decisive, for in raw honey
proteins are present ; and even when bees fed on pure honey or sugar
manufacture wax, it may be derived from the broken-down proteins
of their own bodies.
It is probable that in the formation of fats the carbo-hydrates
are first split up to some extent, and that the fats are then con-
structed from their decomposition products, oxygen being lost in
the process, since fat is much poorer in oxygen than carbo-hydrate.
But the chemistry of the transformation as it takes place in the body
is still imperfectly known, and all that can be done here is to indicate
one or two of the ways in which chemists conceive that it may occur.
The formation of the glycerin component of the neutral fats from
carbo-hydrates would appear to present little difficulty. In dis-
cussing the formation of glycogen from glycerin (p-536), it was stated
that two molecules of glycerose (glycerin aldehyde), a triose or sugar
with three carbon atoms, can be condensed to form a hexbse or sugar
with six carbon atoms like dextrose, from the condensation or union
of a number of molecules of which, with abstraction of water, glycogen
is built up. The reaction can be worked equally well in the reverse
direction — that is, from the hexose dextrose two molecules of glycerin
aldehyde can be formed, and then from each molecule of the alde-
hyde, by reduction, a molecule of the alcohol glycerin. As a matter of
fact, it has been demonstrated that glycerin is produced when the cor-
responding aldehyde is brought into contact with minced liver.
As regards the fatty acid components of the fats, it will be seen from
the schematic representation of the katabolism of dextrose on p. 544
that acetic acid, a fatty acid, is represented at one of the stages as being
formed by the oxidation of a molecule of acetaldehyde. Lactic acid
is represented in the same scheme as a previous stage in the decom-
position of dextrose, and lactic acid can be converted into acetaldehyde
and formic acid, the lowest of the same series of fatty acids of which
acetic acid is the next highest member. Thus :
H.COOH
Lactic acid. Acetaldehyde. Formic acid.
Aldehydes (as well as ketones) have a great capacity for entering into
reactions with other substances, and their molecules show also a marked
tendency to combine with one another, forming new compounds by
their condensation. Thus, from two molecules of acetaldehyde one
36
362 METABOLISM, NUTRITION AND DIETETICS
molecule of aldol is formed, which by transposition of certain groups,
becomes butyric acid, the fourth member of the fatty acid series of
which acetic acid is the second member, and palmitic and stearic acids,
which form such important constituents of the ordinary body - fats,
the sixteenth and eighteenth members respectively. By oxidation aldol
becomes /3-oxybutyric acid, which by further oxidation yields aceto-
acetic acid, compounds already referred to in connection with diabetes
(p. 555). The following equations illustrate these reactions:
= CH3.CH(OH) .CH
Acctaldehyde. Acetaldehyde. Aldol.
CH3.CH (OH) .CH2.CHO - CH3.CH2.CHa.COOH
Aldol. Butyric acid.
CH3.CH(OH).CHa.CHO+ O =CH3.CH(OH).CH,.COOH
Aldol. j8-oxybutyric acid.
CHS.CH (OH) .CH2.COOH + O = (CH3.CO) .CHa.COOH + H2O
j8-oxybutyric acid. Oxygen. Aceto-acetic acid. Water.
By reduction aceto-acetic acid is reconverted into /3-oxybutyric acid.
Other aldehydes can react in similar ways, and thus many of the other
fatty acids can be formed.
It may be added that acetone (another of the so-called acetone
bodies which appear in the urine in diabetes mellitus) is easily obtained
from aceto-acetic acid by the splitting off of carbon dioxide. Thus :
(CH3.CO).CHa.COOH =CH3.CO.CH3 + CO2
Aceto-acetic acid. Acetone. Carbon dioxide.
Formation of Fat — (2) From Protein. — Dry protein contains on
the average 16 per cent, of nitrogen and 50 per cent, of carbon, and
urea contains 46 per cent, of nitrogen and 20 per cent, of carbon.
Urea is therefore three times as rich in nitrogen as the protein from
which it is derived, but two and a half times poorer in carbon ; and
less than one-seventh of the carbon of protein will be eliminated
in a quantity of urea sufficient to carry off all the nitrogen. It
is probable that a portion of the remaining carbon may, after passing
through various stages, take its place as the carbon of fat. We
have seen that certain amino-acids derived from proteins can be
converted into dextrose, and that dextrose can be converted into
fat. So that the mere question whether carbon atoms or carbon
chains originally present in protein molecules are ever capable of
appearing in fat molecules can be straightway answered in the
affirmative. But it is still in doubt whether amino-acids can be
transformed into glycerin or into fatty acids, or into both, by
processes which do not involve the production of dextrose from
them. And in any case proof is required that the extent of the
transformation, let the steps be what they may, is great enough
to be satisfactorily demonstrated. In regard to this point it must
be said that absolutely flawless experiments to prove the direct
production of fat from protein seem still to be wanting.
Phosphorus Poisoning and Migration of Fat. — In the experiments
of Bauer, the amount of oxygen consumed and of carbon dioxide
and nitrogen excreted was determined in starving dogs. Phosphorus,
which, as is well known, causes extensive fatty changes in the
organs, was then administered in small doses for several days.
The excretion of nitrogen was doubled, the excretion of carbon
dioxide and the consumption of oxygen diminished to one-half. When
the animals died, in a few days, the organs were all found loaded with
fat. In one case 42-4 per cent, of the solids of the muscles and 30 per
cent, of the solids of the liver consisted of fat. This is much more than
the normal amount. It was assumed that the fat could not have been
simply transferred from the adipose tissue, since the dog had been
starved for twelve days before the phosphorus was given, and died on
the twentieth day of starvation. Now, after such a period of hunger
the amount of fat in the adipose tissue is greatly reduced. It was there-
fore concluded that the source of the fat could cnly have been the
broken-down pro-tern. Since the nitrogen excretion was increased, while
the carbon excretion was diminished, it was supposed that a residue
rich in carbon must have been split off from the proteins, and, remaining
unburnt in the body, must have been converted into fat. Experiments
of this kind are open to criticism on several grounds, but especially on
this : that unless the fat-content of the whole body before the adminis-
tration of the poison is known, it is impossible to be sure that the fat
in a particular tissue has not been increased simply by the transportation
of fat from some other tissue. It has been conclusively shown that
migration of preformed fat does occur, and on an extensive scale, in
phosphorus poisoning. For example, a dog was fed for a time with
sheep's tallow, and fat was laid down in its adipose tissue with the
physical and chemical characters, not of dog's, but of sheep's fat. The
animal was then poisoned with phosphorus, and the fat which accumu-
lated in the liver examined. It also resembled sheep's fat,, as it should
have done had it migrated from the adipose tissue, and not dog's fat,
as it might have been expected to do had it been formed in the hepatic
cells from protein. The ease with which connective-tissue fat — i.e., food
fat — migrates to the liver suggests, with other facts, that the liver has a
special relation to the transformation of this fat into the fat of the organs.
This ' organized ' intracellular fat differs in various ways from the fats
of adipose tissue. Its ' iodine value ' (p. 4) is higher (Leathes), and a
large proportion of it consists of phosphatide lipoids (p. 571.)
The most convincing evidence that fat is not produced in increased
amount under the influence of phosphorus has been obtained by deter-
mining by actual analysis the total fat in animals, then poisoning
similar animals with phosphorus and again estimating the total fat.
Far from being increased, the fat may even be decreased in the poisoned
animals (Taylor, etc.). There is no ground, then, for the assumption
that phosphorus and other substances, like arsenic, antimony, etc., which
bring about so-called ' fatty degeneration ' of the organs, act by causing
or accelerating the transformation of protein into fat. Yet there is good
evidence that they do accelerate the decomposition of protein, or at
least interfere with its normal metabolism, for after phosphorus poison-
ing amino-acids (leucin, tyrosin, glycin) appear in the urine. The
observations of Lusk and his pupils indicate that phosphorus does not
directly increase the amount of protein broken down, but does so
indirectly, by favouring the conversion of the carbohydrate -like radicle
of the protein molecule into leucin, tyrosin, and perhaps fat, and
thereby necessitating an increased consumption of protein.
A celebrated experiment, performed nearly forty years ago, was long
564 METABOLISM, NUTRITION AND DIETETICS
supposed to furnish an absolute proof of the formation of fat from
protein, under strictly physiological conditions, although in a humble
form of animal life. Maggots were allowed to develop from the egg on
blood containing a known amount of fat. The quantity of fat in the
eggs was also known. After the maggots had grown, ten times as
much fat was found in them as had been contained in the blood and
eggs together. The trifling quantity of sugar in the blood was utterly
inadequate to account for the fat, which, it was concluded, must there-
fore have come from the proteins of the blood (Hofmann). It can be
objected to this experiment that no precautions were taken to prevent
the growth of micro-organisms on the blood, and fat might have been
formed by them from the proteins. Further, the fat estimations would
scarcely pass muster according to the present standards.
The experiments of Pettenkofer and Voit, which were supposed to
have demonstrated that in the higher animals also fat is formed from
proteins under normal conditions, are in the same position. According
to them, a dog fed for a time on a liberal diet of lean meat may go on
excreting a quantity of nitrogen equal to that in the food, while there
is a deficiency in the carbon given off. Or if the dog is not in nitrog-
enous equilibrium (p. 602), but putting on nitrogen in the form of
' flesh,' the deficiency in the carbon given off may be too great in pro-
portion to the nitrogen deficit to warrant the assumption that all the
retained carbon has been put on in the form of protein. In either case,
carbon in large amount can only come from the proteins of the food,
and can only be stored up in the body in the form of fat. For lean meat
contains but a trifling quantity of carbon in any other proximate
principle than protein, and the non-protein carbon of the animal body
is only to a very small extent contained in carbo-hydrates or other
substances than fat.
Pfliiger has criticized these experiments, and has shown that lean
meat contains more fat than was supposed, and this is now generally
admitted. He has endeavoured to show that the fat and glycogen in
the meat given to the animals fully accounts for the carbon retained.
Pfliiger, indeed, takes up the position that the fat of the body comes
exclusively from the carbo-hydrates and fats of the food, and not at all
from the proteins. But there is little doubt that in this he has gone too
far, although his criticism has rendered it impossible any longer to appeal
to Pettenkofer and Voit's results as good evidence on the other side.
If none of the supposed quantitative proofs of the conversion of
proteins into fat which have hitherto been brought forward are
free from flaw, the same is true of the alleged qualitative indications
of its possibility and of its actual occurrence. The accumulation
of fat between the hepatic cells caused by phlorhizin is, at the best,
no better evidence than the accumulation within the cells in phos-
phorus poisoning. The formation of adipocere (a cheesy substance,
rich in fatty acids united with calcium or ammonium), sometimes
seen in dead bodies which have remained a long time under water
or in moist graveyards, is largely, if not entirely, due to the fat
akeady present in the parts which have undergone the change,
or to fat removed by the water from other parts of the body.
If any portion of the adipocere represents fat formed from protein,
this transformation may well be credited to the numerous micro-
organisms present, and throws no light upon the question of fat
formation in the normal organism. The fat in the cells of the
THE METABOLISM OF FAT 5^5
sebaceous glands, and of the mammary glands, may be produced
from protein by a transformation of the cell-substance. But abso-
lutely convincing proof is wanting. The old idea that the cells of
these glands underwent a physiological process of transformation
into fat analogous to the fatty degeneration of pathology, and then
broke down bodily into the secretion, has been long since disproved
for milk formation, and is probably erroneous also as regards the
secretion of sebum. The rule which experience has taught, that
a woman during lactation requires an excess of proteins in her food
corresponding not only to the proteins, but also to the fat given off
in the milk, suggests such an origin for the milk-fat, but does not
prove it. Other fat-containing secretions are the ear-wax formed
by glands in the wall of the external auditory meatus, and the
smegma formed by the glands of the prepuce, but nothing is known
of the sources from which the fatty substances are derived.
The Intermediary Metabolism of Fat. — The mechanism and the
stages of the transformation, including the migration, of fats is
not well understood — indeed, not as well as that of the carbo-
hydrates. Many of the tissues contain intracellular, soluble,
fat-splitting ferments called Hpases, especially the liver, the
active mammary gland, and the intestinal mucosa. We have
already seen that there is evidence that these lipases, like some
other enzymes, have a reversible action. They are either fat-
splitting or fat-forming ferments, according to the conditions
(Kastle and Loevenhart). It is stated that the perfectly aseptic
blood does not split ordinary neutral fats, although it contains a
ferment which splits up monobutyrin (glycerin butyrate) into
glycerin and butyric acid.
The question how the fat, after absorption from the intestine,
passes from the blood into the cells, and how it is enabled again to
pass out of the fat-cells when the needs of the tissues call for its
mobilization, cannot at present be definitely answered. It is
possible that just as fat is split in the lumen of the intestine before
being absorbed, and then rebuilt in the epithelium, so it is split in
the blood or in the lymph before being taken up by the fat-cells.
The lipase in these cells would then be capable of synthetizing the
glycerin and fatty acids to fat in their interior. When the fat is
about to pass out of the cells in response to the call, of whatever
nature it is, of the tissues for fat, it may again be split, resynthetized
in the blood, and again hydrolysed for entrance into the tissue
cells. Or it may be carried to the cells in the form of glycerin and
fatty acids, or soaps, in such small concentration as to be harmless,
and there built up again into the original fat, or transformed into
other fats characteristic of the particular tissues, including the fatty
acid components of the phosphatides, or utilized without synthesis
into fat. An alternative hypothesis avoids this series of decomposi-
566 METABOLISM, NUTRITION AND DIETETICS
tions and syntheses by assuming that the fat passes in the lorni of
very fine droplets through the walls of the cells and of the capil-
laries. The reader will observe that we seem to be discussing again,
and almost in the same terms, the question of the absorption of fat
from the intestine. It is indeed at bottom the same question, and
it might be argued that by analogy it should receive the same solu-
tion. Analogy, however, is a dangerous guide in such matters, and
it is even more difficult to secure an unambiguous experimental test
of the manner in which the internal migration of fat is accomplished
than to secure the like for its absorption from the digestive tube.
As to the ultimate fate of the fat, from whatever source it may
be derived, our knowledge may be compressed into very few sen-
tences : Sooner or later it is split and oxidized to carbon dioxide and
water, its energy being converted into heat or, directly or indirectly, into
mechanical or other functional work ; some of the fat absorbed from the
intestine rapidly undergoes this change without entering the fat-cells of
the adipose tissue. A portion of the fat may be changed into carbo-
hydrt&s. This has been proved for the glycerin component ; its possi-
bility must be admitted for the fatty acids, but proof has not yet been given.
Of the intermediate stages by which the fatty acids are degraded
into the simple end products but little is surely known. Included
among these stages must be the compounds with which the forma-
tion of the acetone bodies (p. 562) starts, if and in so far as their
formation is a normal event which is merely unveiled by the dis-
turbance of the ordinary course of the metabolism in diabetes.
Among these intermediate stages must also be included, it is to be
supposed, the compounds, whatever they may be, which act as
connecting links between the currents of fatty acid and of carbo-
hydrate metabolism, and with which the transformation of fatty
acids into carbo-hydrates commences, if this occurs at all.
According to the observations of Knoop, the saturated as well as
some of the other series of fatty acids when oxidized decompose in a very
characteristic way. As already remarked, these acids are made up of a
larger or smaller number of CH8 groups forming a chain which at one
end terminates with a carboxyl (COOH) group, and at the other with a
CH3 group. The carbon atoms in the chain are designated by Greek
letters, c, j8, etc., the a position being that next the carboxyl group,
the /3 position one remove from the carboxyl group, and so on. Accord-
ing to Knoop, the oxidation of the fatty acid chain takes place in such
a way that the chain is shortened by the cutting off from the carboxyl
end the a CH2 group along with the carboxyl group, while in place of the
/3CH2 group there is left a carboxyl group, an operation which might
be fancifully compared to the naval manoeuvre of breaking the enemy's
., CHo.CHo.CHa-CHo. CH..COOH, "
line. Thus from caproic acid e £ y p a we
get by oxidation butyric acid, CHs-CH2.CH,.O >H, carbon dioxide
and water. It appears that the oxidation proceeds in two stages, the
hydrogen of the /3 group being first oxidized with formation of an
THE METABOLISM OF FA T 567
oxyacid oxycaproic acid, C^.CHa.CHg.CHOH.CHg.COOH, which is
then by further oxidation converted, with loss of two carbon atoms,
into butyric acid. The oxidation process may then start afresh on
the /3 group of butyric acid. On the long carbon chains of the higher
fatty acids this operation may be repeated again and again, the chain
losing two atoms of carbon at each attack. If this represents what
occurs in the normal metabolism, the groups cut off may then and there
undergo the fate of the ships isolated by a successful application ofjthe
manoeuvre alluded to, complete destruction — that is to say, oxidation
to the end products carbon dioxide and water, a portion of the energy
of the fatty acid being thus liberated at each oxidation of the /3 group.
Eventually a fatty acid or acids with very few carbon atoms will be
left. There is some reason to think that acetic acid (and perhaps
similar simple acids) may be one of the normal stages in the decom-
position. Thus, butyric acid may first yield by oxidation of the
/3 group the oxyacid /3-oxybutyric acid, CH3.CHOH.CHa.COOH,
which by further oxidation of the /3 group and the cutting off of the a
and carboxyl groups would give CH3.COOH, or acetic acid.
If this is the general course of the oxidation of the fatty acids in
the body, it is to be assumed that numerous intermediate stages
unrepresented in such a simple scheme may exist. Thus it is known,
as has been mentioned more than once in other connections (p. 562),
that /3-oxybutyric acid by oxidation yields aceto-acetic acid, by
losing from the /3 group two atoms of hydrogen which unite with
oxygen to form water. A molecule of aceto-acetic acid contains
the elements of two molecules of acetic acid minus the elements of
one molecule of water. It is therefore possible that aceto-acetic
acid, if it is a normal stage in the katabolism of fatty acids, yields
by its hydrolysis as a further step acetic acid, according to the
equation
CH3.CO.CH2.COOH + H2O=2(CH3.COOH).
Aceto-acetic acid. Acetic acid.
It is worth while, perhaps, to point out once more that even the
relatively simple products now arrived at are not necessarily at
once completely oxidized to their end products. That, it is to be
assumed, will depend upon the needs of the organism. Acetic acid,
for example, when added to blood and perfused through the sur-
viving liver, can be transformed into aceto-acetic acid, and may
thus become the starting-point of new syntheses.
The Liver and Fats. — The liver seemstoplay an important part in
the metabolism of fat, as it does in the metabolism of carbo-hydrates
and of proteins. It contains an oxidizing ferment, /3-oxybutyrase
(or j8-hydroxybutyrase) , which transforms /3-oxybutyric acid into
aceto-acetic acid (Dakin). This oxidation appears to occur in the
normal as well as in the diabetic organism. The liver seems also to
possess the power of transforming aceto-acetic acid into acetone, a
reaction which does not involve an oxidation, and this may also be
accomplished by means of an enzyme. But it is not at all likely
5<>8 METABOLISM, NUTRITION AND DIETETICS
that acetone forms a stage in the normal katabolism of the fatty
acids or of the /3-oxyacids derived from them. The importance of
the liver in the metabolism of fats is further indicated by the extent
of the migration of fat to that organ when the fat stores are mobilized
in unusual amount (p. 563). The reason for this migration seems
to be that the fats undergo preparatory changes which facilitate
their utilization by the tissues. For example, there is evidence
that saturated fatty acids are changed in the liver into unsaturated
acids, which are then carried to the organs to be metabolized.
The desaturation may serve the purpose of facilitating the rupture
of the long carbon chains, or their capacity for entering into reac-
tions with other substances, at the points where double links exist
between carbon atoms (p. 556).
Non-Nutritive Functions of Fat. — In connection with the metabo-
lism of fat, it ought to be noted that, in addition to their value as
reserve material for the nutrition of the body, the deposits of fat
under the skin and in other situations perform important functions
in protecting delicate structures from mechanical injury, in facili-
tating their movements upon each other, and in hindering the loss
of heat. It would doubtless be a gross exaggeration to say that the
mechanical and physical properties of the fat depots are as im-
portant in comparison to their chemical relations as is the case for
the bones and ligaments, but it would be an error not less gross to
consider them as of little account. It will even, perhaps, be
thought not unworthy of mention, from the point of view of the
propagation of the race, that in the human species, at least, the
amount and distribution of the cutaneous fat play a part of some
consequence in the aggregate of qualities which determine the
physical attractiveness of the individual, especially of the female,
although the standard in this regard varies widely in different
communities.
It is perhaps partly because the fat depots have important
mechanical functions that the fat reserve is far less mobile than the
glycogen reserve. The semi-solid panniculus adiposus, the fatty
tissue around the great nerve trunks, between the muscles, around
the eyeball, on the soles of the feet, etc., possesses as a protective
packing the good qualities of a water cushion with none of its dis-
advantages. But if the fat-cells were subject to sudden depletion, as
the hepatic cells are — nay, in still greater degree, since they contain
hardly any protoplasm — they would never serve for such a function.
Of course, in the emergency of starvation, when even the glands
and the muscles themselves are wasting, the fat reserves are neces-
sarily mobilized, let their mechanical functions suffer as they may.
Obesity. — The proportion of the total mass of the body which is made
tip of fat varies greatly in different individuals, and often in the same
individual at different stages in life. When the accumulation of fat
THE METABOLISM OF FAT 569
passes beyond a certain point it causes obvious changes in the contours
of the body, and often some embarrassment in its movements. This
condition is termed obesity. It is extremely difficult to say when the
condition oversteps the physiological boundary and becomes actually
pathological. Some individuals who are notoriously stout are noted
also for their intellectual activity, and may not fall below the average
even in the ordinary kinds of physical effort. It would be an exaggera-
tion to speak of such persons as suffering from a disease. In other cases
the pathological stamp is clearly imprinted upon the metabolic anomaly
which leads to the overfilling of the fat depots. This is perhaps best
illustrated in those cases of extreme obesity in children where, in spite
of the intense metabolism associated with growth, with the restless
muscular activity characteristic of that age, and with the relatively
great surface through which heat is lost, great quantities of fat continue
to be put on. Muscular activity by itself is no certain antidote to or
• prophylactic against obesity, and it is a mistake to suppose that the
condition is exceedingly rare among manual workers sufficiently well
paid to be able to gratify their tastes in the quality and quantity of
their food. Statistics or rough estimates covering the whole of the
hand-workers of a country throw no light on such a question, for few
indeed are the lands where the masses of the people have such well-filled
purses that they are able to nourish themselves according to their wishes.
While it is true that the great majority of normal individuals (although
not all, since even in the fattening of stock for market some animals are
rejected as bad feeders) can be compelled to lay on fat when overfed
with fat and especially with carbo-hydrates, and prevented from taking
much exercise or from losing heat freely, the most important factor in
the excessive storing of fat by human beings leading a free life seems to
be an anomaly in the metabolism which permits the machine to be run on
less than the usual amount of fuel. From the point of view of thermo-
dynamics the fat man, in very many instances at least, grows fat and
fatter because his body is a machine whose ' efficiency ' is greater than
the normal — that is to say, a machine which is capable of doing a given
amount of work and of keeping itself in repair with a food intake of
smaller heat value than is usually needed. Whether this anomaly is to
be considered a metabolic fault or a metabolic virtue depends largely
upon the ease with which the intake is adjusted to the actual require-
ment of the body. If the adjustment is rendered accurate, the man
with the anomalous tendency to put on fat, the adiposophil, ashe might
be called, is in all probability just as well off in every physiolog ical sense
on a smaller diet than a so-called normal individual of the same age,
weight, and daily routine, on a larger quantity of food, and on this
smaller diet he does not become fat. In this connection it may be
recalled that, in speaking of the blood-flow in the hands and feet (p. 127),
which are in this relation to be regarded as essentially an ' outcrop ' ,
of the cutaneous circulation, it was pointed out that some healthy
persons have habitually small flows and a habitually cool skin which
perspires little, in comparison with others living practically the sam e life;
It was suggested that this difference in the blood-flow through the skin,
which of course would correspond with a difference in the rate of heat
loss, and therefore in the rate of heat production, may be correlated with
a difference in the intensity of the metabolism and the intake of food.
The difficulty of adjusting the appetite to the actual physiological
requirement is perhaps the real anomaly in adiposophilia. Several
factors seem to be involved in the group of sensations comprised under
appetite and hunger (Chapter XVIII), and the onset and intensity of
these sensations are unquestionably influenced by habit. The real
570 METABOLISM, NUTRITION AND DIETETICS
question in many cases of obesity may be not why the metabolism is
managed so parsimoniously — that is, in the physiological sense, so
thriftily — but why the fat man or the man tending to become fat still
experiences so strong a desire for food after he has eaten what in pro-
portion to his metabolic wants is enough, whereas the man with no
tendency to obesity is no longer hungry after he has eaten an amount
of food sufficient for the requirements of his tissues. Is there here
perhaps an anomaly in the nervous mechanism in virtue of which, for
instance, the gastric hunger contractions are more readily initiated
and less easily stilled than in the normal person ? It is recognized
that in the usually much more serious anomaly of the carbo-hydrate
metabolism, diabetes mellitus, the nervous element may be important.
The influence of the loss of certain of the internal secretions on the
deposit of fat will be alluded to in the next chapter.
In the treatment of obesity the factor of appetite and hunger control
has to be specially kept in mind. Bulky but comparatively innu-
tritious food, such as green vegetables, e.g., in the form of salads, should
form an important constituent of the dietary, since the mere distension
of the stomach staves off hunger. The total heat value of the food
must be reduced gradually. Carbo-hydrates must be largely excluded,
and also fats, although a certain amount of fat, say in the form of
butter, is permissible and even beneficial as aiding in the passage of
the food along the digestive tube. Alcoholic beverages are in general
contra-indicated, because alcohol, as an easily oxidizable substance,
protects the carbo-hydrates and fats from oxidation, and perhaps also
because the normal oxidative power of the tissues may be depressed by
its habitual use. On the other hand, tobacco smoking, which has some
power of inhibiting the gastric hunger contractions, may be permitted.
Muscular exercise, cold baths, light clothing both during the day and
at night, and a cool environment, are favourable to the reduction of
fat by increasing the consumption of material and the loss of heat,
just as a sedentary life in an overheated house in a person predisposed
to obesity, and eating too much for his requirements, favours the
putting on of fat. But if the appetite of the patient is allowed to
govern the intake of food, the increased decomposition brought about
by exercise, etc., is very likely to be balanced by an increased ingestion,
and no progress will be made.
Metabolism of Sterins or Sterols. — It has been previously stated
that cholesterin appears to be the only representative of the sterins
in the higher animals. Its source and function have been much
discussed of late years. As to its source, there seems to be no
reason to believe that any part of the cholesterin of the tissues is
formed from decomposition products of ordinary fats, carbo-
hydrates, or proteins. It is probably entirely derived from the
cholesterins of animal, and the phytosterins of vegetable food. On
this assumption, its metabolism, unlike that of the great groups of
food substances, is carried on in a closed circuit. Evidence that
it can be synthesized from other substances in the body is lacking.
No increase in the cholesterin has been observed during the develop-
ment of eggs, and the cholesterin content of growing chickens
appears to correspond to the sterins taken in the food (Gardner).
The portion of the cholesterin which is ingested in the form of esters
THE METABOLISM OF FAT 571
is probably split, with liberation of the fatty acid, in the course of
digestion. But if this be so, cholesterin esters are again formed
in the tissues, for the cells and the blood contain both cholesterin
esters and free cholesterin. While some cholesterin is excreted in
the faeces (p. 423), there is evidence that a portion of the cholesterin
of the bile may be reabsorbed, a ' circulation ' of cholesterin taking
place analogous to the circulation of bile-salts. The appearance of
cholesterin in the bile has been connected by some writers with the
destruction of erythrocytes in the liver, or the conveyance of the
products of their decomposition to that organ (p. 21), but there
are no means of distinguishing between the cholesterin set free from
blood-corpuscles and that liberated from other cells. Since it is
contained in all cells, every cell may be supposed to contribute
something from time to time to the cholesterin excretion.
As to the office of the tissue-cholesterin, it can only be suggested
that a substance so ubiquitous must be important. There is some
evidence that cholesterin, free or combined, plays a part in con-
ferring on the cells those peculiarities in their permeability upon
which their functions, and indeed their integrity, depend. Free
cholesterin, for instance, hinders the haemolytic action of the
saponins (p. 28), apparently by forming compounds with them.
Whether it or its esters are actually concentrated at the surface of
the cell, and contribute to the formation there of the so-called
' lipoid ' envelope, is not definitely known, although there are facts
in favour of this idea.
Metabolism of Phosphatides. — The lecithins, which are the best-
known members of this class of compounds, have been already
described (p. 366). They are built up of glycerin, fatty acids,
phosphoric acid in the form of glyceryl-phosphoric acid, and a
nitrogenous base cholin. There is some reason to think that the
lecithins of the tissues are, in part at least, not free, but combined
with proteins or with carbo-hydrates. Other bodies belonging to
the phosphatide group are kephalin, a constituent of nervous tissue
and of yolk of egg, cuorin found in heart muscle, etc.
It is probable, as stated in the chapter on Digestion, that the
phosphatides of the food are hydrolysed in the alimentary canal
with liberation of the glycerin, fatty acids, and the other com-
ponents. It is not known whether they are resynthesized in the
intestinal wall, but it is more probable that they pass directly to
the tissues, where they can be utilized for building up the phos- "
phatides of the cells. Cholin is found in small quantities free in the
tissues, and also, it is said, in the blood-plasma. Glyceryl-phos-
phoric acid has also been obtained in small amount from various
tissues. The other components of lecithin are, of course, never
wanting, and there can be no doubt that the cells possess the power
of reconstructing phosphatides from such materials. They can do
572 METABOLISM, NUTRITION AND DIETETICS
more than this: they can prepare the 'building-stones 'themselves.
For even when the ingestion of phosphatides in the food is excluded,
or the intake is so small as to be negligible, the formation of phos-
phatides in the body goes on apparently without check. An instance
of this will be given on a future page in discussing experiments on
the relative value of different proteins for nutrition and growth.
A very striking observation has been recorded by McCollom, who
fed three hens on a diet almost free from fat. In about three and a
half months they laid fifty-seven eggs, containing over 9 per cent, of
phosphatides. Calculation showed that here, first of all, fats or their
components must have been constructed from carbo-hydrates.
Then the nitrogenous component of the phosphatides (cholin in the
case of lecithin, at least) must have been obtained from some source,
possibly from an amino-acid by the addition of methyl groups
(CH3), of which cholin, OH.H2C.H2C -N<3 (trimethyl-oxyethyl-
\ ^
OH
ammonium hydroxide) contains three.
SECTION III. — METABOLISM OF PROTEINS.
Blood-Proteins. — The two chief proteins of the plasma, serum-
globulin and serum-albumin,* must, as has been already pointed out,
be recruited from proteins absorbed from the intestine and for the most
part, at any rate, profoundly altered in its lumen and in their passage
through the epithelium which lines it. Even when proteins are being
actively absorbed, the plasma, after the blood-proteins have been
separated, contains no substances which give the biuret reaction
(p. 449). So that the peptones, which can be demonstrated in the
intestinal contents, suffer great changes before or during their
absorption. The physiological reasons for this alteration are in a
measure known, and have already been alluded to in connection
with the digestion of proteins. No doubt the far-reaching decom-
position of the protein molecule may to some extent facilitate the
absorption of protein food. No doubt also it is imperative that
such comparatively slightly hydrolysed products as peptone, and
particularly proteose, should not appear in quantity in the blood,
for when injected they cause profound changes in that liquid, one
expression of which is the loss of its power of coagulation, and are
rapidly excreted by the kidneys, or separated out into the lymph.
But the passage of the food from the stomach is so gradual an affair,
the quantity of digesting protein present at one time in any loop
of intestine is so small, and the rush of blood which irrigates the
* It is probable that plasma contains a mixture of different albumins anf1
globulins.
METABOLISM OF PROTEINS 573
active mucosa is so large, that the concentration of peptone or
proteose necessary to produce injurious effects could hardly in any
case be realized. Again, there is no evidence thai the simpler
decomposition products of further hydrolysis are not in equal con-
centration as poisonous as proteose and peptone.
Apart from any influence which it may have in favouring absorp-
tion, the complete shattering of the protein molecule has a double
significance. In the first place, as already pointed out, the food-
proteins cannot be used directly in the upbuilding and repair of the
protoplasm (p. 448), since the tissue-proteins differ from them and
from each other in the amount and nature of the amino-acids and
other groups in their molecule (p. 2). Secondly, under ordinary
dietetic conditions a surplus of nitrogen in the protein food has to
be got rid of by being converted into urea without being built up
into the tissue substance. Here we come upon the fundamental
fact that the protein katabolism is not a single uniform process.
Two forms may be distinguished which are essentially independent
in course and character. One kind varies extremely in its quantita-
tive relations, according to the amount of protein in the food. Its
chief end-products are urea, representing the nitrogen, and inorganic
sulphates, representing the sulphur of the proteins. Since this form
of katabolism, as we shall see directly, is not essentially connected
with the life and nutrition of the living substance, it is termed
exogenous. The other variety is practically constant in amount
for one and the same individual, and independent of the quantity
of protein in the food. Its characteristic end-products are creatinin
and neutral sulphur. This form of protein katabolism is essentially
an expression of the waste of the living substance itself, and is
therefore spoken of as endogenous.
Some have supposed that the intestinal mucosa has as one of its
special functions the resynthesis of a great part of the digestive
decomposition products into the proteins of the blood-plasma. If
this is the case, these proteins must be again decomposed in the
cells of the various tissues in order that the ' building-stones ' may
be recombined to form the tissue-proteins. For the proteins of the
organs are not the same as those of the blood, and the proteins of
different organs differ characteristically from each other. The
significance of the synthetic function of the intestinal wall would
then lie in this: that from the varying mixture of amino-acids, etc.,
derived from the food-proteins an always uniform and suitable'
protein mixture (the blood-proteins) is fabricated for the feeding
of the tissues. Experiments intended to test this hypothesis have
hitherto yielded a negative result. No accumulation of protein in
the wall either of the intestine in situ or of the isolated surviving
intestine has been detected during absorption of the decomposition
products of protein. An alternative assumption, and superficially
at least a simpler one, is that no more extensive synthesis of proteins
574 METABOLISM, NUTRITION AND DIETETICS
occurs in the wall of the alimentary canal than is necessary for the
needs of the tissues composing it, and, perhaps in addition, for the
maintenance of the normal composition of the plasma, and that the
decomposition products of the proteins are mainly absorbed as such,
and pass in the blood to the tissues for which they are destined. If
this is the case, the blood-proteins can no longer be looked upon as
representing the main current of protein supply for the organs, but
rather the store of protein material proper to the circulating tissue
blood itself, and which confers on it certain chemical and physio-
chemical properties (e.g., the due degree of viscosity) necessary for
its function. Slowly accumulated, under ordinary conditions, and
slowly consumed, this protein store may, of course, be at the dis-
posal of the organs in an emergency — for instance, in starvation —
or may be rapidly recruited from the organ-proteins, as after
haemorrhage, just as in prolonged hunger the proteins of skeletal
muscle may be utilized to feed the heart. That the blood-proteins
can serve as nutritive material for the cells without undergoing
digestion in the alimentary canal is well shown by the observations
of Carrell and Burrows on the growth of isolated tissues in a medium
composed of clotted blood-plasma. But, as previously pointed out
in another connection (p. 449), a portion, and probably a large
portion, of the digested protein is absorbed from the intestine by
the blood in the form of amino-acids. Considerable quantities of
these compounds can be separated by dialysis from blood drawn
off during the absorption of proteins or by the process of vivi-
diffusion (p. 48) (Abel). Among these amino-acids, glycocoll,
alanin, glutaminic acid, and leucin, have been identified. While
the quantity of amino-acids in the blood, which is very small in the
fasting animal, is decidedly increased during protein digestion, it
is probable that even in starvation amino-acids derived from the
decomposition of the body-proteins are not entirely lacking. The
normal concentration of amino-acids in the general blood of man and
of the dog is about o-i per cent. — i.e., about the same as that of
dextrose, and it may be nearly twice as great in the portal blood
of dogs after a heavy protein meal. The amino-acids are very
rapidly absorbed by the tissues from the blood, and can be demon-
strated in muscles and other organs as free amino-acids. They
accumulate there in much greater concentration than that in which
they exist in the blood. Accordingly, the tissues take them up from
the blood by some other process than simple diffusion (Van Slyke) .
It has been surmised that amino-acids constitute the form in which
proteins are transported from tissue to tissue, as well as the form in
which proteins are normally utilized by the cells.* Although this
cannot be regarded as yet established, there is reason to believe that
• Recent experiments of Abel tend to rehabilitate the old view that some
protein is absorbed as proteoses, which can also be isolated from the tissues-
METABOLISM OF PROTEINS
573
the amino-acids play a great part in protein metabolism, perhaps as
great a part as the dextrose does in the metabolism of the carbo-
hydrates. There is some evidence that serum-albumin is more
directly related to the proteins of the food than serum- globulin.
And it is said that during starvation the albumin is relatively
diminished, and the globulin relatively increased. It is, of course,
not at all improbable that the plasma-proteins have a double source
— organ-proteins on the one hand, food-proteins on the other. In
any case, it is certain that serum-albumin and serum-globulin
cannot be interchangeable without far-reaching decomposition, for
their composition is very different. The globulin, e.g., yields glyco-
coll, but the albumin does not. That the plasma-protein mixture
maintains a very constant composition in the face of wide variations
in the composition of the food-protein is indicated by the following
experiment :
A horse fed mainly on hay and oats was bled to the amount of
6 litres, and in the total protein of the serum the content of tyrosin and
glutaminic acid was determined. In order to eliminate the influence
of remains of the food in the digestive canal, nothing was given to the
animal for a week. Then 6 litres of blood were again removed, and the
tyrosin and glutaminic acid in the serum-protein again estimated.
The horse was now fed with gliadin (one of the prolamins or alcohol-
soluble proteins obtained from flour), a substance which contains 36-5 per
cent, glutaminic acid and 2-37 per cent, tyrosin — that is, about the
same amount of tyrosin as the serum-protein, but about four times as
much glutaminic acid. The serum-protein was again analyzed for the
two amino-acids after this diet. The results of one experiment are
shown in the table :
Normal.
After 8 Days'
Hunger.
After Feeding
with 1,500
Grammes
Gliadin.
After Feeding
again with 1,500
Grammes
Gliadin.
Tyrosin -
Glutaminic acid
2-43
8-85
2 -60
8-20
2-24
7-88
2-52
8-25
No increase in the glutaminic acid content of the serum-protein
occurred, although, owing to the loss of blood, much new serum-protein
must have been formed. If the amino-acids of the gliadin were used
without change to build up the new serum-protein, three-quarters of
the glutaminic acid must have been superfluous, and the nitrogen of
this portion may have been straightway changed into urea and excreted.
But the possibility that the glutaminic acid, or a portion of it, may-
have been changed into other amino-acids in the body cannot be
excluded. In the case of some of the amino-acjds it has been shown
that such a transformation occurs (p. 613) (Abderhalden).
The high degree of independence of the food and body proteins is
still more clearly exhibited in the table from Abderhalden on p. 576,
in which the proteins of milk are compared with some of the proteins
which must be formed from them in the body of the suckling. The
numbers represent percentages of the weight of each protein.
576
METABOLISM, NUTRITION AND DIETETICS
Living and Dead Proteins. — Carried to the tissues, the decomposition
products of the food -proteins, or the regenerated proteins of the plasma,
which in ordinary language are still to be regarded as dead material,
are built up into the living protoplasm, at any rate to the extent neces-
sary to make good its waste. In this form they sojourn for a time
within the cells, and then they become dead material again. The
nature of this tremendous transformation has, of course, been the
subject of speculation, but the truth is that we do not understand
wherein the difference between a living and a dead cell, between a living
and a dead particle in one and the same cell, really consists. All we
know is that now and again a protein molecule or an aggregate of such
molecules incorporated in the colloid mass which constitutes the proto-
plasm of a muscle-fibre, or a gland-cell, or a nerve-cell, must fall to
pieces. Now and again a molecule of protein, hitherto dead (or perhaps,
to speak moBe correctly, hitherto not a constituent of living protoplasm.
Since protoplasm is certainly more than protein), or a molecule of a
particular amino-acid, or perhaps a polypeptide group intermediate in
complexity between amino-acid and protein, coming within the grasp
of the molecular forces or chemical affinities of the living substance, is
caught up by it, takes on its peculiar motions, acquires its special powers,
and is, as we phrase it, made alive. Each cell has the power of selecting
and, if necessary, further decomposing or further synthesizing the
protein materials offered to it ; so that a particle of serum-albumin or a
mixture of amino-acids may chance to take its place in a liver-cell and
help to form bile, while an exactly similar particle or mixture may
furnish constituents to an endothelial scale of a capillary and assist in
forming lymph, or to a muscular fibre of the heart and help to drive on
the blood, or to a spermatozoon and aid in transferring the peculiarities
of the father to the offspring. And just as a tomb and a lighthouse, a
palace and a church, may be, and have been, built with the same kind
of material, or even in succession with the very same stones, so every
organ builds up its own characteristic structure from the common
quarry of the blood.
i
!
Milk-
Albumin.
Serum-
Albumin.
Serum-
Globulin.
O
1
E
Histon
(Thymus).
_d
1
3
M
Glycocoll -
O
O
0
3'5
O
3-o
o-5
26-0
4'7
Alanin
0-9
2'5
2-7
2'2
4'2
3-6
3'5
6-6
1 "5
Valin
I'O
0-9
some
some
I'O
I'O
0-9
Leucin
10-5
19-5
20 -o
18-7
29-0
15-0
ii-8
21-4
7-1
Serin
0'2
—
0-6
0-6
some
—
—
Cystin
O'O7
—
2 '3
0-7
0-3
—
—
—
0-6
Asparaginic acid
Glutaminic acid
I '2
I I'O
I'O
IO'O
7-7
4'4
1-7
2-0
8-0
~.
0-8
IO'O
3'7
Lysin
5-8
—
—
4'3
—
6-9
—
Arginin
4-8
—
—
—
5 '4
—
*5'5
0-3
—
Phenylalanin -
2'4
3-1
3-8
2'O
2 '2
3-9
—
Tyrosin -
4'5
I'O
2'I
2*5
i «5
3'5
5*2
°'34
3'2
Prolin
4-0
I'O
2 '8
2*3
i'5
1-7
3-4
Histidin -
2-6
—
—
I I'O
—
METABOLISM OF PROTEINS 577
It is not any difference in the kind of protein offered them which
determines the difference in structure and action between one organ
and another. In this quarry alongside of the plasma proteins the tissue
cells find what is probably more important for their individual nutrition,
the building-stones of the shattered food-protein molecules. They are
only under exceptional circumstances confronted with intact molecules
of food -proteins. ' The body cells do not know what the kind of food
was ' (Abderhalden). In the case of the more highly developed tissues,
at least, no mere change of food will radically alter the structure of the
cells, nor even, as we have seen, the composition of the tissue proteins.
A cell may be fed with different kinds of food, it may be overfed, it may
be ill-fed, it may be starved; but its essential peculiarities remain as
long as it continues to live. What may be called its organization, per-
haps at bottom a more or less metaphorical expression for its essential
physico-chemical make-up, dominates its nutrition and function.
' We must assume that many of the enigmatical properties of living
matter depend upon the activity of intact protein molecules. We can
obtain some idea of the possible variety in "the combinations of the
'* building-stones " of the proteins by recalling the fact that they are as
numerous as the letters of the alphabet, which are capable of expressing
an infinite number of thoughts. Every peculiarity of species and every
occurrence affecting the individual may be indicated by special com-
binations of the "building-stones " — that is to say, by specific proteins.
Consequently we may readily understand how peculiarity of species
may find expression in the chemical nature of the proteins constituting
living matter, and how they may be transmitted through the material
contained in the generative cells ' (Kossel). Add to the great variety
of compounds rendered possible by the enormous number of permuta-
tions and combinations of the protein ' building-stones,'* the still greater
variety rendered possible by the fact that the quantitative relations of
given amino-acids may vary greatly in different proteins, and it will be
seen what a practically infinite power of functional adjustment and
reaction, correlated with a practically infinite variety of chemical
changes in the midst of which the cell still preserves its specificity
through and through, may be conferred upon the living substance by
its content of protein.
Some have supposed that the protein of the living substance is es-
sentially different from dead protein, especially in possessing a character-
istic instability, a prodigious power of dissociation and reconstruction.
All the older theories which attempted to explain this alleged difference
require revision in accordance with the newer chemistry of proteins,
and speculations on the subject are probably in any case premature
till the constitution of the proteins is thoroughly understood. In the
meantime it is enough to say that the velocity of the reactions into
which the proteins of living protoplasm or their constituent amino-
acids may enter must depend upon intracellular conditions, which may
vary rapidly and within wide limits. For example, enzymes may be
present in greater or smaller concentration, or be activated and aided
more or less powerfully by other substances, or by a more or less favour-
able chemical reaction of the medium. The protein itself, too, or such
part of it as is ready for decomposition, may exist in a physical con-
dition now more and again less favourable to the attack of the enzymes.
* Twenty different amino-acids, each used only once, but in a different order,
would be capable of forming about 2,000,000,000,000,000,000 (two thousand
million times a thousand millions) of different polypeptides, all containing the
various amino-acids in the same proportions (Abderhalden) .
578 METABOLISM, NUTRITION AND DIETETICS
It may not be superfluous at this point to again warn the reader that
protoplasm and tissue -profeins are by no means synonymous. The
physical, physico-chemical, and chemical changes involved in the
katabolism of the colloid aggregates, including water, salts, phosphatides,
sterins, and probably fats and dextrose as well as proteins, to which
the term protoplasm is applied, may be many and complex before the
individual proteins known to the chemist come face to face in the
interior of the cells with the ferments which decompose them. On the
other hand, it has not been proved that in the katabolic processes of the
living substance isolated proteins ever form a stage. It may well be
that without the complete decomposition of the protein molecules, or
even without their complete detachment from the protoplasm, indi-
vidual amino-acids or mixtures of amino-acids, or polypeptide groups,
are cut out of the protoplasmic mass.
It is now necessary to follow, as far as is possible, the steps
in the degradation of the body-proteins. Since there is reason to
believe that these, like the food-proteins, are first split up into the
amino-acids from which they were originally synthesized before
undergoing further decomposition, a study of protein metabolism
is to a great extent a study of the metabolism of amino-acids. In
this study it is for most purposes impracticable, even if it were
desirable, to distinguish between amino-acids directly derived from
the food, and which have not yet been, and may never be, built up
into tissue-proteins, and those derived from the tissue proteins.
There is nothing to indicate that the fate of a given amino-acid,
once it has reached the blood, depends in the least upon its source.
It may be said at once that the katabolism of the amino-acids is not
a single and uniform process, one step in which inevitably follows
another till the final end-products are reached. On the contrary,
certain of the stages may become the starting-points of syntheses,
which may lead back to the original or to another protein, or it
may be to sugar or to fat. The extent of such synthesis, and
even in some degree the stage from which it starts, may be assumed
to depend upon the needs of the tissues and the relative abundance
of protein and of other foods.
Formation of Amino-Acids from Tissue-Proteins. — That amino-
acids are formed in the metabolism of the cells and by the action of
intracellular enzymes is indicated by the fact that proteolytic en-
zymes (proteases) are invariably present in the tissues, and can
be obtained from them by appropriate methods — e.g., by subjecting
the organ in a finely divided state to a high pressure and collecting
the expressed juice. Not only do unicellular organisms, like leuco-
cytes, yeast cells, and bacteria, which must naturally depend upon
themselves alone for all enzymatic reactions, yield ferments which
have the power of splitting proteins, peptones, and polypeptides
into amino-acids, but their existence has been demonstrated in
practically all the organs of the higher animals and man. When a
piece of liver, e.g., is removed with aseptic precautions and kept at
579
body-temperature, extensive auto-digestion occurs, and ammonia
and other basic substances, glycin, and tryptophane, appear among
the products. Tyrosin appears so early that it is scarcely possible
to doubt that it must be a product of protein decomposition in the
liver-cells under normal conditions — a decomposition which could
be observed also in the organ in situ were the circumstances as
favourable. The circumstances are less favourable in an organ
whose circulation is going on, because the amino-acids are removed
by the blood as they are formed. Further, it is to be assumed that
the regulation of the ferment action, which is a characteristic
property of the normal cell, becomes feebler the longer it is with-
drawn from normal conditions. Similar autolytic processes have
been observed in the spleen, muscle, lymph-glands, kidneys, lungs,
stomach wall (independently of pepsin), thymus, and placenta;
also in pathological new growths like carcinoma, in the breaking
down of which and in the removal of such exudations as occur in
the alveoli in pneumonia, these proteolytic ferments seem to play
a part. It is to be assumed that the syntheses of the proteins or
their products, which are scarcely less characteristic of the tissue
cells than the decompositions effected by them, are also due to
the action of separate intracellular ferments or upon the reversed
activity of the proteolytic ferments.
More direct proofs of the production of amino-acids in the tissues
are not lacking. A rare condition known as cystinuria has been
alluded to on a previous page (p. 488). Here there is a continuous
excretion of the sulphur-containing amino-acid cystin in the urine.
Sometimes the cystin is accompanied by other amino-acids, as
leucin and tyrosin, a condition which might be called amino-
aciduria. Cystinuria, while of course resulting from a gross anomaly
in metabolism, is of little clinical importance unless the sparingly
soluble cystin should form calculi somewhere in the urinary tract.
The most plausible explanation of the condition is that in the
normal course of the metabolism each of the ' building- stones ' of
the proteins is sooner or later further decomposed by special fer-
ments, and that for some reason the ferment which acts on cystin
is absent, or if it is still produced, the conditions are more or less
unfavourable to its action. Unable to take its place in the meta-
bolic current, except in so far as it can be utilized to form taurin,
and therefore taurocholic acid — for this property it has not lost —
cystin becomes a chemical outcast in the body of the cystinuric
individual, and is got rid of by the kidneys as an ' unemployable.'
By comparing the amount of cystin excreted with the amount
ingested in the food-proteins and with the (undiminished) amount
contained in the tissues (especially the hair and the nails, since
keratin is exceptionally rich in cystin), it has been shown that a
portion of the cystin in the urine must have come from the tissues
5So METABOLISM, NUTRITION AND DIETETICS
(Abderhalden). Observations on animals in prolonged starvation
afford additional evidence. The hair and nails continue to grow
and to maintain the high cystin content, and taurocholic acid con-
tinues to be excreted. In like manner glycin continues to be pro-
duced and to unite with cholic acid to form the glycocholic acid of
the bile.
There are other and more striking proofs that glycin can be
formed in the body in large amount. For example, as already
stated (p. 481), when benzoic acid is ingested it is not excreted as
such in the urine, but coupled with glycocoll as hippuric acid.
Thus —
C6H5.COOH + CH2(NH2).COOH - H2O =C6H5.CO.NH.CHa.COOH
Benzoic acid. Glycocoll. Hippuric acid.
Benzoic acid, therefore, meets glycin in the body, and combines
with it, as fatty acids meet glycerin and combine with it. Even
starving animals fed with benzoic acid excrete large quantities of
hippuric acid. Yet their tissues, as shown by analysis after death,
yield as much glycocoll as starving animals which have received no
benzoic acid, and excreted little or no hippuric acid. Many other
acids which are totally foreign to the body are, when ingested,
paired in the same way with glycocoll and excreted in the urine.
Even substances whose chemical nature does not permit of a direct
union with the glycin are often altered by oxidation or reduction
till they can unite with it, and then the coupling takes place, and
the conjugated acid is eliminated by the kidneys. The paired or
aromatic sulphuric acid which we have already recognized as a
normal constituent of the urine affords another instance of this
coupling. Cystein among the derivatives of proteins, and glycu-
ronic acid (p. 482) among the derivatives of carbo-hydrates, can
also unite in the same way with numerous compounds. There is
some evidence that the physiological significance of this process is
that the toxicity of the foreign substances, or, as in the case of the
aromatic sulphuric acid of the urine, of substances formed by
bacteria in the intestine, or even produced in the metabolism of the
tissues, is diminished by the pairing.
The place and manner of formation of hippuric acid have been
investigated with the following result : If an excised kidney is per-
fused with blood containing benzoic acid, or, better, benzoic acid
and glycin, hippuric acid is formed. Oxygen is required, for if the
blood is saturated with carbon monoxide, or if serum is employed
for perfusion, the synthesis does not take place. The kidney cells
must be intact, for if a mixture of blood, glycin, and benzoic acid
be added to a minced kidney immediately after its removal from
the body, hippuric acid is produced, but not if the kidney has been
crushed in a mortar. Nevertheless, there is some evidence that a
METABOLISM OF PROTEINS 581
ferment is concerned, and the known mechanism of similar reactions
in the body scarcely permits the physiologist to acquiesce in any
other explanation. It must not be forgotten that the urinary
constituents which must come into contact with the ferment when
the kidney is crushed may injure or inhibit the enzyme. In
herbivora hippuric acid cannot normally be detected in the blood;
it is present in large quantities in. the urine ; it must therefore be
manufactured in the kidney, not merely separated by it. In certain
animals, as the dog, the kidney is the sole seat of the production
ol hippuric acid. But in the rabbit and the frog some of it must
also be formed in other tissues, for after extirpation of the kidneys
the administration of benzoic acid causes hippuric acid to appear
in the blood. It has, indeed, been recently shown that when the
rabbit's liver is perfused with blood containing benzoic acid, hip-
puric acid is produced. The benzoic acid required for the normal
excretion of hippuric acid comes mainly from substances of the
aromatic group contained in vegetable food, but a small amount is
produced in the body, since hippuric acid does not entirely dis-
appear from the urine in starvation.
The differences which may exist in the metabolism of different
groups of animals is well illustrated by the fact that in birds, when
benzoic acid is given in the food, it unites not with glycin, but with
ornithin, a derivative of arginin, forming not hippuric acid, but
ornithuric acid (dibenzoyl-ornithin) . A much more important
instance of such a difference will be seen when we come to consider
the formation of urea and uric acid.
The method by which the presence and the production of glyco-
coll in the body are demonstrated by coupling it with benzoic acid,
and so saving it from decomposition and bringing it to excretion,
can also be applied to other amino-acids. If instead of fishing
with the bait benzoic acid we fish with a bait caUed brom-benzol or
bromo-benzene (C6H5.Br), a substance derived from benzol by
the substitution of an atom of bromine for an atom of hydrogen,
we capture the amino-acid cystein in the form of a compound
called mercapturic acid, produced by the union of brom-benzol with
cystein and acetic acid, with oxidation and loss of water. In other
words, when this substance is administered, mercapturic acid is
excreted in the urine, the cystein, which is very unstable and readily
changes into cystin (p. 360), being thus preserved from decom-
position. Another instance in which amino-acids (tyrosin and
phenylalanin), which would normally be decomposed and so escape
detection, come to the surface by being excreted in the urine, has
a'ready been alluded to in connection with alkaptonuria (p. 483).
In this condition, which seems to have no serious significance so
far as the well-being of the patient is concerned, not only does the
taking of food containing the aforesaid amino-acids lead to an
582 METABOLISM, NUTRITION AND DIETETICS
increased excretion of homogentisinic acid, but even in starvation
this substance still continues to appear in the urine. Since homo-
gentisinic acid is undoubtedly formed from tyrosin and from phenyl-
alanin, this observation constitutes a convincing proof that these
amino-acids are produced from tissue-proteins. A striking illus-
tration of the fact that the amino-acids of the tissues are not simply
a store of reserve material derived directly from the alimentary canal
is the failure of a period of starvation to make any impression upon
their amount. They normally constitute 2 to 4 per cent, of the dry
weight of the tissues, and if anything, tend somewhat to increase
in the tissues of a starving animal.
Fate of Amino- Acids in the Body. — The problem of the kata-
bolism of proteins is thus reduced to the question, What becomes of
the amino-acids ? Where, how, by what stages, and to what end-
products are they decomposed ? Some, possible or probable steps
in their metabolic history have been already suggested in dealing
with the intermediary metabolism of carbohydrates (p. 542).
Something more will have to be said of the where and the how of
their chemical degradation in treating of the place and manner of
urea formation. As to the end-products by which they are repre-
sented in the final balance-sheet of the bodily economy, the answer
is easy. The amino-acids, whatever intermediate stages they may
pass through, whatever cleavages, oxidations, or reductions they may
undergo, yield eventually carbon dioxide, water, and comparatively
simple nitrogen-containing substances, which after further changes
appear in the urine principally as urea, and in birds and reptiles as
uric acid. When amino-acids are fed to mammals or introduced
parenterally, a very large proportion of the nitrogen appears in the
urine as urea. The same is true when, instead of simple amino-
acids, polypeptides, like glycyl-glycin, alanyl-alanin, or leucyl-leucin,
are given. When amino-acids are administered to birds, the great
bulk of the nitrogen is excreted in the form of uric acid. Whether
in mammals, and if so to what extent, uric acid is also one of the
nitrogenous end-products of the decomposition of ordinary proteins
or of the amino-acids which they yield, are moot questions. In
any case, the most important and characteristic source of the uric
acid in mammals and the other groups of animals whose chief
nitrogenous end-product is urea, is not the ordinary proteins, but
the nucleins which form constituents of the nucleo-proteins.
We have no definite information as to the production of water from
the hydrogen of the tissues, except what can be theoretically deduced
from the statistics of nutrition (p. 620). A few words will be said
a little farther on about the production of carbon dioxide from
proteins; we have now to consider the seat and manner of formation
of the nitrogenous metabolites. And since in man and the other
mammals urea contains, under ordinary conditions, by far the
METABOLISM OF PROTEINS 583
greater part of the excreted nitrogen, it will be well to take it
first.
Formation of Urea. — The starting-point of all inquiries as to the
place of formation of urea is the fact that it occurs in the blood in
small amount (4 to 6 parts per 10,000 in man; 3 to 15 parts per
10,000 in the dog), the largest quantity being found when the food
contains most protein and at the height of digestion, the smallest
quantity in hunger (Schondorff). Evidently, then, some, at least,
of the urea excreted in the urine may be simply separated by the
kidney from the blood; and analysis shows that this is actually
the case, for the blood of the renal vein is poorer in urea than that
of the renal artery, containing only one-third to one-half as much.
If we knew the exact quantity of blood passing through the kidneys
of an animal in twenty-four hours, and the average difference in
the percentage of urea in the blood coming to and leaving them,
we should at once be able to decide whether the whole of fhe urea in
the urine reaches the kidneys ready made, or whether a portion of
it is formed by the renal tissue. Although data of this kind are as
yet inexact and incomplete, it is not difficult to see that all, or most
of, the urea may be simply separated by the kidney.
If we take the weight of the kidneys of a dog of 35 kilos at 160 grammes
(^Oth of the body-weight is the mean result of a great number of
observations in man), and the average quantity of blood in them at
rather less than one-fourth of their weight, or 35 grammes, and con-
sider that this quantity of blood passes through them in the average
time required to complete the circulation from renal artery to renal
vein, or, say, ten seconds, we get about 300 kilos of blood as the flow
through the kidneys in twenty-four hours. Even at 0-3 per 1,000, the
urea in 300 kilos of blood would amount to 90 grammes. Now, Voit
found that a dog of 35 kilos body-weight, on the minimum protein diet
(450 to 500 grammes of lean meat per day) which sufficed to maintain
its weight, excreted 35 to 40 grammes of urea in the twenty-four hours.
If, then, the renal epithelium separated somewhat less than half of the
90 grammes urea offered to it in the circulating blood, the whole excre-
tion in the urine could be accounted for, and the blood of the renal vein
would still contain more than half as much urea as that of the renal
artery. So that the whole of the urea in the urine may be simply
separated by the kidney from the ready-made urea of the blood.
Another line of evidence leads to the same conclusion : that the
kidney is, at all events, not an important seat of urea-formation.
When both renal arteries are tied, or both kidneys extirpated, in a
dog, urea accumulates in the blood and tissues; and, upon the whole,
as much urea is formed during the first twenty-four hours of the
short period of life which remains to the animal as would under
normal circumstances have been excreted in the urine.
Where, then, is urea chiefly formed ? The answer to this question
is that, while some urea is probably produced from amino-acids in
all the tissues, one organ is particularly associated with this function
— namely, the liver.
584 METABOLISM, NUTRITION AND DIETETICS
There is no reason to suppose that the hepatic cells, so far as the
repair of their own protoplasm or the supply of energy for their own
special work is concerned, require to metabolize particularly large
quantities of amino-acids as compared, for instance, with the
muscles. Glycin, however, they must have for the manufacture of
glycocholic.andcystin for the manufacture of thetaurin of taurocholic
acid. In addition, the liver is known to possess the power of utilizing
amino-acids for the formation of dextrose and eventually of glyco-
gen, and a portion of the surplus amino-acids of the food may be
withdrawn from the blood of the portal vein for this purpose, just
as the surplus of dextrose is withdrawn.
The liver contains a relatively large amount of urea, and there is
strong evidence that it is the manufactory in which a great part of
the nitrogenous relics of broken-down proteins, including amino-
acids, reach the final stage of urea. This evidence may be summed
up as follows:
(1) An excised ' surviving ' liver forms urea from ammonium
carbonate mixed with the blood passed through its vessels, while
no urea is formed when blood containing ammonium carbonate is
sent through the kidney or through muscles. Other salts of am-
monium, such as the lactate, the formate, and the carbonate, under-
go a like transformation in the liver. It is difficult, in the light of
this experiment, to resist the conclusion that the increase in the
excretion of urea in man, when salts of ammonia are taken by the
mouth, is due to a similar action of the hepatic cells.
(2) If blood from a dog killed during digestion is perfused through
an excised liver, some urea is formed, which cannot be simply
washed out of the liver-cells, because when the blood of a fasting
animal is treated in the same way there is no apparent formation
of urea (v. Schroeder). This suggests that during digestion certain
substances which the liver is capable of changing into urea enter the
blood in such amount that a surplus remains for, a time unaltered.
These substances may come directly from the intestine ; or they
may be products of general metabolism, which is increased while
digestion is going on ; or they may arise both in the intestine and in
the tissues. Leucin — which, as we have seen, is constantly, or, at
least, very frequently, present in the intestine during digestion —
can certainly be changed into urea in the body. So can other
amino-acids of the fatty series, like glycocoll or glycin, and aspartic
acid, and it has been shown by perfusion experiments that this
change can take place in the liver. Further, the blood of the portal
vein during digestion contains several times as much ammonia as
the arterial blood, and the excess disappears in the liver.
(3) During digestion the blood loses a greater proportion of its
amino-nitrogen (amino-acids) in passing through the liver than in
passing through other organs, as shown by the fact that the excess
METABOLISM OF PROTEINS 585
in the portal blood, as compared with the blood of the hepatic vein,
is greater than the difference between the arterial and the vena
cava blood. Now it has been proved that the liver does not store
amino-acids to an appreciable extent as such, and therefore it must
either have destroyed or condensed them into proteins. There is no
evidence that the liver forms a store of reserve protein from amino-
acids as it does of glycogen from carbohydrates, although this is
possible. But there is good reason to believe that a portion at least
of the amino-acids taken up by the liver is quickly broken down,
and- that urea is formed from them. For when amino-acids were
injected into a vein in such amount that the content of amino-acids
in all the tissues was considerably increased, they disappeared far
more rapidly from the liver than from muscle or kidney, and their
disappearance from the liver was accompanied by an increase in the
urea content of the blood (Van Slyke) .
(4) Uric acid — which in birds is the chief end-product of protein
metabolism, as urea is in mammals — is formed in the goose largely,
and almost exclusively, in the liver. This has been most clearly
shown by the experiments of Minkowski, who took advantage of
the communication between the portal and renal-portal veins
(p. 385) to extirpate the liver in geese. When the portal is ligated
the blood from the alimentary canal can still pass by the round-
about road of the kidney to the inferior cava, and the animals
survive for six to twenty hours. While in the normal goose 50 to
60 per cent, of the total nitrogen is eliminated as uric acid, in the
urine, and only 9 to 18 per cent, as ammonia, in the operated goose
uric acid represents only 3 to 6 per cent, of the total nitrogen, and
ammonia 50 to 60 per cent. A quantity of lactic acid equivalent
to the ammonia appears in the urine of the operated animal, none
at all in the urine of the normal bird. The small amount of urea in
the normal urine of the goose is not affected by extirpation of the
liver. And while urea, when injected into the blood, is in the
normal goose excreted as uric acid, it is in the animal that has lost
its liver eliminated in the urine unchanged.
(5) After removal of the liver in frogs, or in dogs which have
survived the previous connection of the portal vein with the inferior
vena cava by an Eck's fistula (p. 385), the quantity of urea excreted
is markedly diminished, and the ammonium salts in the urine are
increased. When the Eck's fistula is established and the portal
vein tied, without any further interference with the hepatic circula-
tion, the amount of urea in the urine is not lessened to nearly the
same extent, evidently because the substances from which urea is
formed still, for the most part, gain access to the liver through the
hepatic artery and by means of the back-flow which is known to
take place through the hepatic vein. Yet while in normal dogs the
proportion of ammonia to urea in the urine is only 1 :22 to i : 73,
586 METABOLISM, NUTRITION AND DIETETICS
in dogs with Eck's fistula it rises to i : 8 to 1 : 33. If the animals
are kept on a diet poor in proteins, no symptcms may develop for
a considerable time. But if much protein is given, characteristic
symptoms, including convulsions, always appear. These may be
produced by the saturation of the organism with ammonia com-
pounds, which are formed from the proteins as in the normal animal,
but which the liver, with its circulation crippled, is unable to cope
with, and to completely change into urea, although the statement
has been made that when ammonia or ammonium salts are injected
into the blood larger quantities must be present to produce these
symptoms than are found in animals with the Eck's fistula.
Although the portal vein carries to the liver a greater supply of
blood than the hepatic artery (about twice as much, according to
Opitz and Macleod and Pearce), ligation of the latter causes a
greater diminution in the ratio of the amount of urea to the total
nitrogen in the urine than ligation of the former. While the blood
of the hepatic artery is, of course, nearly saturated with oxygen,
that of the portal vein is not half saturated, so that the total quan-
tity of oxygen transported to the liver by the hepatic artery is
actually greater than the quantity transported by the portal vein.
This indicates that a good supply of oxygen is an important factor
in the formation of urea in the liver (Doyen and Dufourt). But
this is no proof that the process by which it is formed is an oxidation.
The work of the liver, like that of other tissues, is no doubt deranged
by lack of oxygen.
(6) In acute yellow atrophy, and in extensive fatty degeneration
of the liver, urea may almost disappear from the urine, and leucin,
tyrosin, and other amino-acids may appear in it along with a much
larger amount of ammonia than normal. Here it may be supposed
that the amino-acids and ammonia formed in the intestine in
the digestion and absorption of proteins, perhaps also amino-groups
formed in the tissues which would normally be culled from the blood
by the hepatic cells for the manufacture of urea, pass unchanged
through the degenerated liver, and are excreted by the kidney.
It would, however, be very easy to overdo this argument ; for it
is sometimes observed that in pathological and experimental condi-
tions in which the liver has suffered severely considerable quantities
of urea continue to be excreted. Urea does not entirely cease to
be produced even when the liver is removed; and it must again
be pointed out that there is reason to believe that the formation
of urea is not a function peculiar to the liver, but one shared prob-
ably with all tissues. The liver certainly does not arrest the whole
of the amino-acids coming from the alimentary canal ; for the non-
protein nitrogen in the muscles is distinctly increased during the
absorption of amino-acids, and the muscular tissue, even when freed
from blood, contains some urea, which in all probability is formed
METABOLISM OF PROTEINS 587
there in the decomposition of amino-acids. Some writers, indeed,
take the view that the muscles, containing as they do three-fourths
of the proteins of the body, and utilizing as they appear to do a
large proportion of the amino-acids of the food-protein, are more
important seats of urea formation than the liver. Yet the fact that
it is far easier to demonstrate this power — e.g., by perfusion experi-
ments— for the liver than for such tissues as the muscles, renders it
difficult to avoid the conclusion that in the preparation of an end-
product so important as that in which the great bulk of the nitrogen
leaves the body, a certain degree of specialization has been developed,
and that this preparation has been largely entrusted to a special
organ. And, while it may be true that larger amounts of amino-acids
are taken up and utilized by the muscles than by the liver under
certain conditions, this does not show that amino-groups removed
from the amino-acids in the muscles may not be largely transferred
to the liver before being changed into urea. Further, the transforma-
tion of amino-acids into dextrose (and glycogen) may be assumed to
entail a considerable absorption of amino-acids by the hepatic cells.
Processes by which Urea is formed. — In the case of only one of the
amino-acids derived from proteins can urea be obtained by a simple
process of hydrolytic cleavage. This is arginin (o-amino-5-guanidin-
w-valerianic acid) — that is to say, normal valerianic acid,
CH3.CH2.CHa.CHa.COOH,
i y ft a
in which an amino group is attached to the o carbon atdm, while
guanidin NrT2^C.NH is attached to the S carbon atom (p. 566)-
When arginin is hydrolysed by barium hydroxide it yields urea and
ornithin (diamino-valerianic acid), half of the nitrogen of the arginin
appearing in each. Thus,
NHa
aO >
Arginin.
NHa
.CH.C
=O+ NH2.CHa.CHa.CHa.CH.COOH
UreaT Ornithin.
The amount of arginin, and therefore the amount of urea which can be
artificially obtained in this way, varies extremely with the different
proteins. Thus, salmin, a protamin (p. 2), prepared from the milt
of salmon, yields 84-3 per cent, of its weight of arginin, while the
casein of cow's milk yields only 4-8 per cent., and gluten-fibrin, one of
the proteins of wheat, only 3 per cent. In the body the hydrolysis of
arginin to urea and ornithin is accomplished by the ferment arginase
(Kossel and Dakin). This ferment is found in the liver, and also in
many other organs. The urea formed in this way appears very
rapidly in the urine. The ornithin itself is then more slowly transformed
into urea. Since the ordinary food-proteins are poor in arginin, the
588 METABOLISM, NUTRITION AND DIETETICS
amount of urea which can possibly be formed in mammalian metabolism
by this process cannot be large, even if most of the arginin, as is the
case when it is fed to an animal, is transformed into urea.
There is no reason to suppose that urea can be directly split off from
the other amino-acids with which we are concerned. A comparison
of their constitutional formulae with that of urea (or with that of uric
acid) shows that a more far-reaching decomposition must take place
before products are obtained from which urea (or uric acid) can be
formed. Urea has been artificially obtained from protein by oxidation
with an ammoniacal solution of permanganate at body-temperature.
When the protein is first split into its cleavage products, and these are
then oxidized, a very large amount of urea is produced — e.g., as much
as 3 grammes of urea from 10 grammes of glycin.
While these facts suggest possible ways of formation of urea in the
body, we cannot assume that what happens in the test-tube must
happen in the tissues. The best evidence is to the effect that in the
body the removal of the amino-group (NH8) in the form of ammonia
from the amino-acids is the essential step in the formation of at least
a great part of the urea, which is then synthesized from ammonia and
carbonic acid . The possibility exists that this deamini zation (or deamidi-
zation) of the amino-bodies is the result of hydrolysis, or of oxidation, or
of reduction, or of a combination of these processes. Evidence has been
found that in the case of some of the amino-acids the deaminization is
associated not with hydrolysis in which hydroxyl is substituted for
the NH2 group, but with oxidation (Neubauer) . But this has not been
shown to hold good for all amino-acids. In either case, however,
whether the deaminization process is oxidative or hydrolytic the nitrogen
is split off as ammonia, and it is to such ammonium compounds as have
been already mentioned as being transformed into urea when circulated
through an excised liver (p. 584) that we have to look for the source of,
at any rate, a large portion, of the urea. Ammonia in the form of
carbonate or carbamate is constantly found in the blood (p. 585). The
excess of ammonia in the portal blood, which, however, is not admitted
by all observers to be very large or very constant, has been interpreted
as indicating that a considerable decomposition of iamino-acids with
liberation of the amino-groups occurs in the intestinal lumen or the
intestinal wall. It is not established beyond doubt that ammonia is
itself present in the protein molecule, or that its liberation in the
hydrolysis of proteins can take place except at the expense of further
decomposition of amino-bodies. It has been shown, however, that a
great part of the ammonia in the blood is produced in the decomposition
of protein in the digestive tube by putrefactive bacteria (Folin and
Denis). This is a necessary part of the reaction by which phenol and
indol are formed in the intestine.
It has been generally taught that the deaminization of the surplus of
amino-bodies takes place chiefly in the liver, the extra nitrogen being
thus ' shunted ' out of the blood-stream before it has had a chance to
reach the tissues. It would seem more advantageous in the light of
our present knowledge that a large and, so to say, a miscellaneous
assortment of amino-bodies should be placed at the disposal of the
tissues to facilitate the selection of those which are indispensable.
We have seen that tissues such as muscle can and do take up amino-
acids when protein is digested in the intestine, and it is very probable
that they take up not merely the relatively small amount necessary to
replace their wear and tear, but also a portion of the surplus, which
after deaminization in the cells takes its place as a source of energy
to drive the machine. The nitrogen in the form of ammonia may pass
METABOLISM OF PROTEINS 589
back into the blood, and may thus be carried to the liver for conversion
into urea. It is not necessary, however, to suppose that all of the
nitrogen must perforce make this journey before being changed into
urea. There is evidence that all the tissues share to some extent with
the liver the power of forming urea just as they share with the liver the
power of splitting off NH2 from the amino-bodies. It may be that
the liver surpasses other tissues in its deamidizing power just as it seems
to surpass other tissues in its power of transforming ammonium com-
pounds into urea. But this does not prevent at least a considerable
proportion of the amino-substances absorbed from the intestine from
passing into the general circulation. It is of importance to remark
that such hydrolytic cleavages as are associated with the splitting of
protein into amino-acids, etc., only slightly reduce the available energy
of the compounds. In so far as the liberation of the nitrogen from
the amino-acids is also accomplished by hydrolytic cleavage (sup-
posedly by a ferment desaminase), the residue, relatively rich in carbon,
will still be available for yielding to the body by its oxidatien an amount
of energy not much less than could be obtained from the original protein.
The combination of ammonia with carbon dioxide and the conversion
of the carbonate into urea, perhaps through the intermediate stage of
ammonium carbamate, does not require any oxidation. Thus,
/OH /O.NH, /O.NH4 /NHfi
,
\OH \O.NH4 \NH2 \NH2
Carbonic acid. Ammonium Ammonium Urea.
carbonate. carbamate.
Another way in which some of the urea may be produced is by the
direct formation of ammonium carbamate in the katabolism of amino-
acids without the preliminary liberation of ammonia. By the loss of a
molecule of water the carbamate would then become urea. But if, as
there is every reason to believe, a part of the carbonaceous residue is
converted into carbo-hydrate, a certain amount of oxidation must
occur in the transformation.
Such compounds as guanin, sarkin or hypoxanthin, xanthin, uric
acid, and creatin, used to be cited as among the possible intermediate
substances between protein and urea. But while there is now complete
evidence that the first three bodies can be and are converted into uric
acid, there is nothing at all to indicate that they are stages on the
way to urea. Uric acid is, indeed, very closely related to urea, and
can be made to yield it by oxidation outside the body. Not only so,
but it is, in part at least, excreted as urea when given to a mammal
by the mouth and it replaces urea as the great end-product of nitro-
genous metabolism almost wholly in the urine of birds and reptiles.
But none of these things can be admitted as evidence that in the
normal metabolism of mammals uric acid lies on the direct line from
protein to urea. Creatin exists in the body in greater amount than
any of these, muscle containing from 0-2 to 0-4 per cent, of it; and the
total quantity of nitrogen present at any given time as creatin is not
only greater than that of the nitrogen present in urea, but greater
than the whole excretion of nitrogen in twenty-four hours. But
although there are facts which indicate that creatin is an important
derivative of the decomposed tissue proteins (p. 597) there is no
evidence that it is related to urea formation.
Summary : Here may be summed up the most probable view of the
normal decomposition in the body of the amino-acids, whether they undergo
decomposition without being incorporated into the tissue proteins or proto-
590 METABOLISM, NUTRITION AND DIETETICS
plasm, or are liberated as the protoplasm breaks down. The first step may
be conceived of as the splitting off of the NH2 group, which yields ammonia.
The ammonia is transformed into urea. The non-nitrogenous residue
after removal of the amino-group differs according to the amino-acid.
Some of the amino-acids, such as alanin, glycin, prolin and aspartic acid,
yield substances which can be changed into dextrose in the body, as shown
by the increased amount of dextrose excreted by phlorhizinized animals
when the amino-acids are fed to them.* Other amino-acids — e.g., lysin,
histidin and tyrosin, phenylalanin, etc., have such a chemical structure
that the non-nitrogenous compounds derived from them cannot form dextrose.
From certain amino-acids, such as histidin, phenylalanin, tyrosin and
leucin, it has been shown that acetone bodies can be derived. These facts
explain how sugar can be formed and the acidosis associated with the
acetone bodies developed in diabetes, even when the diet consists of protein
only or when the patient is living on his own tissues.
Formation of Uric Acid. — Uric acid, like urea, is separated from
the blood by the kidneys, not to any appreciable extent formed in
them. In birds, and often in man, it can be detected in normal
blood. It is present in increased amount in the blood and transuda-
tions of gouty patients, in whose joints and ear-cartilages it often
forms concretions. ' Chalk-stones ' may contain more than half
their weight of sodium urate.
As to the place and manner of formation of uric acid, it has already
been stated that in birds, after extirpation of the liver, the uric acid
excretion is greatly diminished, and that ammonium lactate appears
instead in the urine. The simplest interpretation of this result is,
that ammonia and lactic acid pass into the urine because they can
no longer be utilized for the synthesis of uric acid. Chemical
schemata can indeed be constructed, which show more or less
plausibly how lactic acid, pyruvic acid (p. 545) and other substances
reacting with ammonia or with the urea derived from it (and birds
form some urea) might yield uric acid. It has been further stated
that when blood containing ammonium lactate is circulated through
the surviving liver of the goose, an increase in the uric acid content
of the blood occurs. As demonstrated by control experiments, this
increase is too great to be due merely to the sweeping out of pre-
viously formed uric acid from the hepatic cells ; also the feeding of
lactic acid, pyruvic acid, and other organic acids leads to an increased
output of uric acid. The story seems fairly complete, although
criticisms have not been lacking. It has been suggested, for instance,
that for some reason the loss of the liver leads to acidosis, an in-
creased production of acids, especially lactic acid, in the organism ;
that ammonia, which would otherwise be employed in the formation
of uric acid, is needed to neutralize these acids, and that the appear-
ance of this ammonia in the urine is only a secondary consequence
of the elimination of the liver. The deficiency in the uric acid
* In animals under the influence of phlorhizin sugar is formed from all
substances capable of producing it in the organism.
METABOLISM OF PROTEINS 59*
excreted, it is said, is therefore due, not to inability on the part of
the remaining tissues to form uric acid, but to the absence of the
ammonia which they require for its formation. This criticism, if
it were admitted as against the current interpretation of such ob-
servations on the bird's liver, could scarcely be denied some validity
as against the current interpretation of similar observations on the
results of interference with the mammalian liver. It is therefore
important to point out that there is still the same deficiency of uric
acid when alkali is administered to neutralize the acids, although
ammonia ought now to be available. There can be no question,
then, that the liver in birds is the seat of an extensive synthesis of
uric acid, and there is little doubt that ammonia compounds are
essentially concerned in the process, whatever the role of the lactic
or other acids may be. A similar synthetic formation of uric acid
from ammonia and a derivative of lactic acid may take place in
mammals, and probably exclusively in the liver, but it is of much
less importance. Another way in which uric acid arises both in
mammals and in birds is by the splitting and oxidation of nucleins.
This is by far the most important mode of formation in mammals,
as synthesis is the chief mode of formation in birds. In both groups
of animals the oxidative production of uric acid takes place, not in
any particular organ, but in the tissues in general, including the liver.
It has been shown that when air is blown through a mixture of
splenic pulp and blood, uric acid is formed from purin bodies already
present in the spleen. When the quantity of these is increased by
the decomposition of nucleins induced by slight putrefaction, the
yield of uric acid is also increased. Uric acid is also formed by the
perfectly fresh surviving spleen, liver, and thymus in the presence
of oxygen, and the quantity is increased when purin bodies are
artificially added.
Sources of the Uric Acid. — It is well established that in the bird
it arises both from amino-acids derived from the hydrolysis of
protein and from nuclein compounds and their derivatives in the
food and tissues. The amino-acids constitute by far the greatest
source of uric acid in these animals and in the reptiles, and it is
practically certain that the course of the decomposition of the
amino-acids and the form in which nitrogen is liberated from them
in its transformation into this end-product are not essentially differ-
ent from what obtains in the formation of urea in the mammal and
the amphibian. This is sufficiently illustrated by the rdle played by
ammonia and ammonia compounds in the production of uric acid
in the birds and their congeners. In the mammal, the taking of
food rich in nucleated cells, and therefore in nucleo-proteins and
nucleins, the characteristic conjugated proteins of nuclei (thymus
gland, pig's pancreas, and herring roe), or of food rich in purin
bases (Liebig's meat extract), increases the quantity of uric acid in
592 METABOLISM, NUTRITION AXD DIETETICS
the urine. The increase is mainly due to the production of uric
acid from the nuclein substances of the food. But this is not the
only source of the uric acid, since extracts of the thymus gland
containing only traces of nucleins or nucleic acid cause, when in-
jected, a characteristic increase in the uric acid excretion, just as
the entire gland does when taken by the mouth. And during the
period of increased nitrogen excretion occasioned by a meal contain-
ing protein, the increase in the uric acid occurs particularly in the
hours immediately following the ingestion of the food, and does not
last so long as the increase in the urea. Now, the nucleins of the
food are comparatively little affected during the earlier stages of
digestion (Hopkins and Hope). Whether in mammals any portion
of the uric acid comes from amino-acids is still in doubt, but there
are facts which indicate that a fraction of it may do so. We may
conclude, therefore, that in the mammal, as well as in the bird, a
portion of the uric acid, although certainly a far smaller portion in
the mammal, is derived from bodies other than the nuclein substances
of the food — that is io say, from the nuclein substances of the tissues
contained particularly in the cell-nuclei and probably from the
ordinary proteins of both food and tissues. The portion derived
irom the proteins may be assumed to be that small fraction which
has already been spoken of as synthetically formed.
Metabolism of the Nucleic Acids and Purin Bases. — Our know-
ledge of the metabolism of the nucleo-proteins and nucleins has
been greatly augmented in recent years. When nucleo-protein is
digested by gastric juice, a certain amount of protein is easily split
off and hydrolysed to peptone and the other ordinary products
of proteolysis. An insoluble residue of nuclein remains. This is
acted upon with difficulty by gastric juice, although eventually an
active juice will split it up also. By the action of pancreatic juice,
or by heating with dilute acids, it is more easily hydrolysed, yielding
a further quantity of protein along with nucleic acid. This second
fraction of protein, which is split off with so much more difficulty
than the first, undergoes proteolysis in the usual way. The result-
ing amino-acids no doubt take their place in the general metabolism
precisely like the amino-acids derived from ordinary proteins, and
yield the same end-products. As regards the nucleic acid (or rather
acids, since different nucleo-proteins contain different nucleic acids),
pancreatic juice is practically inert, although succus entericus can
effect a partial hydrolysis. For their complete decomposition more
drastic treatment is required — namely, heating with hydrochloric
acid in a sealed tube. Thus treated, nucleic acids yield a number
of components, out of which they may be assumed to be built up,
as the proteins are built up out of amino-acids, etc. The charac-
teristic components are purin bases (adenin, C5H3N4.NH2; guanin,
C6H,N4O.NH2; hypoxanthin, C6H4N4O; and xanthin, C5H4N4O2);
METABOLISM OF PROTEINS
593
pyrimidin bases (uracil, C4H4N2O2; cytosin, C4H3N2O.NHa; thymin
C4H3NaOa.CH3); phosphoric acid and a carbo-hydrate group.
Some of the nucleic acids contain all these components; they are
sometimes spoken of as the true nucleic acids. In others certain of the
components are absent, and to these nucleic acids the name nucleotids
has been applied. The purin bases are always present. The carbo-
hydrate group varies in different nucleic acids, being in some a hexose
(p. 537), in others a pentose (p. 487). The pentose d-ribose is especially
often met with. It is probable that the nucleotids are merely simpler
decomposition products of the true nucleic acids. Thus, inosinic acid,
a nucleotid first isolated from meat extract, yields phosphoric acid,
<2-ribose, and the purin base hypo xan thin. The nucleotid guanylic acid
found in the pancreas yields phosphoric acid, d-ribose, and the purin
base guanin. There is evidence that nucleic acids may be built up out
of a number of nucleotid groups, and for this reason they have been
termed polynucleotids (Levene). The purin bases have a very close
chemical relationship to uric acid, which, like them, is characterized by
the possession of a group called the purin nucleus. For convenience
of reference the atoms composing the purin nucleus are numbered,
and the purin bodies are named with reference to the position of the
carbon atom or atoms at which oxygen or the amino-group (NH2) is
introduced. Purin consists of the nucleus with H atoms introduced at
the points shown in the constitutional formula. Adenin is a 6-a.mino-
purin — i.e., purin in which NH2 replaces the H attached to C(«j. Guanin
is 2-amino-6-oxypurin, NH2 being united with C@) and oxygen with C«j)
in purin. Uric acid is 2, 6, 8-trioxypurin — i.e., purin in which oxygen
is united to the carbon atoms 2, 6, and 8. Hypoxanthin is 6-0 xy purin,
oxygen being introduced at the position of C(6) in purin. By removal
of the amino-group from, adenin hypo xan thin is formed. Xan thin is
2, 6, dioxypurin, oxygen being introduced at C(2> and C(6) in the purin
molecule. Xan thin can be derived from guanin in the same way as
hypoxanthin from adenin.
C(6) - N(T)
N(3) C,4)— N(9)
N=CH
HC C— NH
;CH
N— C— N
Purin nucleus.
Purin.
N =C.NH2
I I
HC C— NH
>H
N— C— N
Adenin.
NH2.C
NH— CO
L
NH
NH— CO
Jo c!-:
N=C.OH
NH— CO
•NH HC C— NH
o
NH
CH
CO
N — C— N
Guanin.
NH— C— NH
Uric acid.
>
CH
N— C— N
Hypoxanthin.
NH— C— N
X anthin.
)CH
Besides the purin bases combined in the nuclein substances, purin bases
and uric acid are widely spread in the tissues in the free state, although
in very small amounts.
A portion of the intake of purin bodies is therefore ready formed,
especially in the animal constituents of the food, and does not require
the decomposition of nucleic acid for its liberation. The nuclei of
vegetable cells contain nucleo-proteins, and accordingly can contribute
to the purin intake. The most interesting contribution of vegetable
38
594
METABOLISM, NUTRITION AND DIETETICS
origin has been previously alluded to (p. 481) — namely, the methyl
purins forming the active "principles of tea, coffee, and cocoa, caffein,
or i, 3, 7-trimethylxanthin (C8H10N4O2), theobromin, or 3, y-dimethyl-
xanthin (C7H8N4O2), and theophyllin, or i, 3 - dimethylxanthin
(C6H8N402).
CH3.N— CO
CO C— N.CH3
>H
CH,.N— C— N
Caffein.
NH— CO
:o
CH3.N — C
Theobromin.
CH3.N— CO
. 482), and its complete independence of the
changes in the total nitrogen excretion, show that it has a. different
significance in protein metabolism from the urea. Evidence is accumu-
lating that it is especially in the metabolism of the organized or tissue
protein that the product eventually excreted as creatinin arises ; in other
words, that it represents especially the nitrogenous waste connected
with the wear and tear of the bodily machinery, while urea represents
also, and under ordinary conditions of diet chiefly, the nitrogen of the
surplus amino-acids which are not utilized in the building of new or the
repair of old tissue elements. The fact that the amount of creatinin
excreted by different persons seems to be related to the weight of active
tissue in the body, excluding fat, is in favour of this suggestion, and
METABOLISM OF PROTEINS 599
there is other evidence pointing in the same direction ; for example
in ordinary circumstances creatin is either absent from the urine or
present in very small amount, except in young children. When, how-
ever, the decomposition of tissue-protein is abnormally increased, as in
starvation, in fevers, in women after delivery, while involution of the
uterus and the associated destruction of a considerable mass of smooth
muscle is taking place, creatin appears in larger quantities in the urine,
perhaps because it can no longer be all converted into creatinin. Now,
the increased excretion of creatin in starvation can be prevented by
giving carbo-hydrate food, which is known (p. 606) to lead to sparing
of tissue-protein (Mendel and Rose). That the depletion of the body
of carbohydrate is in some way related to the elimination of creatin
is further shown by the fact that creatinuria is associated with diabetes
and with the action of substances like phlorhizin, hydrazin, phosphorus,
etc., all of which cause carbo-hydrate deficiency. Something more is
involved, however, for under conditions of diet which produce acidosis
(an increase in the hydrogen-ion concentration of the blood), creatin
appears in the urine no matter how rich the food may be in carbo-hy-
drate. For example, a diet of oats and maize, which are typical acid-
producing foods, causes creatinuria in rabbits, which promptly disappears
when carrots, a base-producing food, are added (Underhill).
The statement that the content of the urine in creatinin is increased
by muscular work may indicate that the muscular machine wears out*
faster during activity than during rest, or perhaps only that already-
formed creatin leaves the muscles in greater amount when the blood-flow
in increased; but recent observations tend to show that this statement
may require revision.
As to the manner in which creatin is changed into creatinin in the
body, a highly suggestive fact is the presence of ferments in various
organs which possess this power. Ferments also exist which can
decompose both creatin and creatinin. The existence of such enzymes
is presumptive evidence that the changes which they are capable of
producing actually occur in the organism ; but the seat of the changes
if they do take place, and their metabolic significance, are unknown.
Creatin when given by the mouth or injected into the blood does not
cause any increase in the urinary creatinin, nor when administered in
moderate quantities does it seem to be excreted as creatin. Like urea,
creatinin, and amino-acids, it is taken up very rapidly by the muscles.
Creatinin, on the other hand, when added to the food, causes an increase
in the creatinin of the urine.
Intracellular Ferments — Autolysis. — As to the agencies by which
the decomposition of the proteins is carried out in the cells, we have
already spoken of the oxidizing cell ferments, or oxydases (p. 272).
Reducing ferments, or reductases, are also known, and can be ex-
tracted from most organs, if not all. Like oxydases, they act in a
weakly alkaline medium, causing in the presence of hydrogen such
reductions as the formation of nitrites from nitrates. There is some
evidence that one and the same ferment may act as an oxydase or
a reductase according to the conditions. Recent researches have
brought to light in addition hydrolytic intracellular ferments, which
split up proteins very much in the same way as the proteolytic
ferments of the digestive juices.
The significance of these autolytic enzymes in the normal metabo-
6oo METABOLISM, NUTRITION AND DIETETICS
lism of proteins has been already discussed (p. 578) ; indeed, so many
of the chemical reactions of the body have been found to depend
upon enzymes that modern physiology may at first thought seem
almost to have reverted to the position of Van Helmont and his
school in the seventeenth century, who resolved all difficulties by
murmuring the magic word ' ferment.' No fewer than eleven fer-
ments have been stated to be present and active in the liver alone
— viz., a proteolytic and a nuclein-splitting ferment, a ferment
which splits off ammonia from amino-acids, a milk-curdling ferment,
a fibrin ferment, a bactericidal ferment, an oxydase, a lipase, a
maltase, a ferment called glycogenase, which changes glycogen into
dextrose, and an autolytic ferment. In the presence of such an
array of enzymes the organs might seem to be little more than
incubators in which the ferments do their work. It must not be
supposed, however, that the intracellular ferments, whether they
cause decomposition or synthesis, oxidation or reduction, work in-
dependently of what, for want of a better name, we must call the
organization of the cell. We may be sure they are the servants
and not the masters of the protoplasm, and that a drop of an extract
containing intracellular ferments has very different powers from a
living cell. ' It is not in the existence of the ferments, but in their
combined action at the proper time and in the proper intensity, that
the riddle of metabolism lies ' (Hober) .
Summary. — At this point let us sum up what we have learnt as
to the relation between the approximate principles of the tissues and
the proximate principles of the food. Inside the body we recognize
representatives of the three groups of organic food-substances in a
typical diet — proteins, carbo-hydrates, and fats. But we should
greatly err if we were to imagine that the three streams of food-
materials have flowed from the intestines into the tissues each in its
separate channel, neither giving to nor taking from the others.
The fats of the body may, indeed, in part be composed of molecules
which were present as fat in the food ; but they may also be formed
from carbo-hydrates, and probably from proteins. The carbo-hydrates
of the body — the glycogen of the liver and muscles, the sugar of the blood
—may undoubtedly be derived from carbo-hydrates in the food, but they
may also be derived from proteins and from fats (certainly from their
glycerin constituent, perhaps from the fatty acids as well) . The pro-
teins of the body come mainly, if not solely, from the proteins of the food.
Although, of course, neither fats nor carbo-hydrates can by themselves
form protein, being devoid of nitrogen, it is possible that products
arising in the intermediary metabolism of either may, by combining
with nitrogenous groups, be tranfsormed into amino-bodies, which can
then take part in the synthesis of proteins. In any case there is no
doubt that both carbo-hydrates and fats can economize proteins and
shield them from an overhasty metabolism.
STATISTICS OF NUTRITION
60 1
SECTION IV. — STATISTICS OF NUTRITION — THE INCOME AND
EXPENDITURE OF THE BODY IN TERMS OF MATTER.*
Preliminary Data. — The office of the food is to maintain the con-
stituents of the body upon the whole in their normal proportions. A
knowledge of the chemical composition of the body is, therefore, an
important datum in the consideration of the statistics of its metabolism.
The body of a man analyzed by Volkmann had the following composition :
Inorganic substances Pn^lmatte; - - 6« per cent.
{Carbon 1 8 -4 pe r cent . ^
NSro"!nn 11 I; [-9-7 ..
Oxygen 6-0 ,, J
The muscles, the adipose tissue, and the skeleton form nearly four-
fifths of the total body-weight in the adult. The following table shows
the percentage amount of each of these tissues in a man, a woman, and
a child (Bischoff) :
Man.
Woman.
New-born
Child.
Voluntary muscles
Adipose tissue
Skeleton
Rest of body
41-8
18-2
15-9
24-I
35-8
28-2
15-1
20-9
23-5
13-5
I5'7
47'3
The nitrogen is contained chiefly in the muscles, glands, and nervous
system, and in the constituents of the connective tissues, which yield
gelatin, various mucoids, and elastin. The ordinary proteins make up
about 9 per cent, of the weight of the body, or 22 per cent, of its solids ;
the albuminoids or sclero-proteins (gelatin-yielding material, etc.) (p. 2)
about 6 per cent, of the body-weight. Nitrogen exists in proteins to
the extent of 16 per cent., so that the 6-5 kilos of protein of a yo-kilo
body contain about I kilo of nitrogen.
The carbon is contained chiefly in the fat, which forms a very large
proportion of the water-free substance of the body, and in the proteins.
A small amount is present as calcium carbonate in the bones. In the
body of a strong young man weighing 68-6 kilos, Voit found the following
quantities of dry fat in the various tissues :
Adipose tissue
Skeleton
Muscles
Brain and spinal cord
Other organs
Total -
8809-4 grammes.
2617-2 ,,
636-8
226-9 .»
73-2
- 12363-5
equivalent to 18 per cent, of the whole body-weight, or 44 per cent, of
the solids. In dry fat rather more than 75 per cent, of carbon is present,
and in protein about 50 to 55 per cent. ; so that while the fat of the body
analyzed by Voit contained more than 9 kilos of carbon, only about a
third of this amount would be found in the proteins.
* The income and expenditure of the body in terms of energy are considered
in Chapter XII.
602 METABOLISM, NUTRITION AND DIETETICS
In the fat there is, roughly speaking, 12 per cent, of hydrogen, in
proteins only 7 per cent. ; so that from three to four times as much
hydrogen is contained in the fat of the body as in its proteins.
Oxygen forms about 12 per cent, of fat, and 20 to 24 per cent, of
proteins; the protein constituents of the body, therefore, contain about
as much of its oxygen as the fat.
Of the inorganic salts, calcium phosphate, Ca3(PO4)2, is much the
most abundant, owing to the large amount of it in bone, in the ash of
which it is found to the extent of 83 per cent., along with 13 per cent,
of calcium carbonate.
INCOME AND EXPENDITURE OF NITROGEN — THE NITROGEN
BALANCE-SHEET.
Nitrogenous Equilibrium. — It is a matter of common experi-
ence that the weight of the body of an adult may remain approxi-
mately constant for many months or years, even when the diet varies
greatly in nature and amount. And not only may the weight remain
constant, but the relative proportions of the various tissues of the
body, so far as can be judged, may remain constant too. Here it
is evident that the expenditure of the body must precisely balance
its income: it must lose as much nitrogen as it takes in, otherwise
it would put on flesh; it must lose as much carbon as it takes in,
otherwise it would put on fat. Or, again, the body may be losing
or gaining fat, giving off more or less carbon than it receives, while
its ' flesh ' (its protein constituents) remains constant in amount,
the expenditure of nitrogen being exactly equal to the income.*
In both cases we say that the body is in nitrogenous equilibrium.
A starving animal or a fever patient, on the other hand, is living
upon capital, the former entirely, the latter in part ; the expenditure
of nitrogen is greater than the income. A growing child is living
below its income, is increasing its capital of flesh. In neither case
is nitrogenous equilibrium present.
The starving animal, as long as life lasts, excretes urea, kreatinin,
and other nitrogenous substances, and gives off carbon dioxide;
but its expenditure, and especially its expenditure of nitrogen, is
pitched upon the lowest scale. It lives penuriously, it spins out
its resources; its glycogen goes, its fat goes, a certain part of its
protein goes, and when its weight has fallen from 25 to 50 per cent,
it dies. At death the heart and central nervous system are found
to have scarcely lost in weight ; the other organs have been sacrificed
to feed them. Fig. 199 shows the percentage loss of weight and
the proportion of the total loss which falls upon each of the organs
of a cat in starvation (Voit).
* For long experiments extending over many days the nitrogen balance
may be considered as practically the same as the protein balance, but this
is not necessarily true of short periods of time, since the stock of nitrogen
present in the body in other forms than proteins, although relatively small,
is subject to variations.
STATISTICS OF NUTRITION
603
For the first day of starvation the excretion of urea in a dog or
cat is not diminished; it takes about twenty- four hours for all the
nitrogen corresponding to the proteins of the last meal to be elimin-
ated. On the second day the quantity of urea sinks abruptly;
then begins the true starvation period, during which the daily output
of urea remains constant or diminishes very slowly until a short time
before death, when it rapidly falls, and soon ceases altogether. An
increase in the excretion may precede the final abrupt decline (pre-
mortal increase). This seems to indicate the time at which all the
available fat has been used up, and after which protein is no longer
' spared ' by the fat.* If the animal has little fat in its body to
begin with, the rise in the urea excretion takes place even after the
first few days. So long as the fat lasts the rate at which it is
42-1 Muscle
Z6-Z Fat
8-7 Skin
S-5 Bones
4- -8 Liver
3-6 Blood
Z-0 Mestines
0-6 Kidneys •
^0-5 Spleen
0-3 Lungs
0-1 Pancreas
Oil Testes
(O-/ Brain & Cord
{(?•/ Heart
Fig. 198. — Diagram showing Loss of Weight of the Organs in Starvation. The
numbers under I. are the percentages of the total loss of body-weight borne by
the various organs and tissues. The numbers under II. give the percentage loss
of weight of each organ calculated on its original weight as indicated by com-
parison with the organs of a similar animal killed in good condition.
destroyed — as estimated from the amount of carbon given off minus
the carbon corresponding to the broken-down proteins — remains
very nearly constant after the first day. The fat to a certain extent
economizes the proteins of the starving body, but however much
fat may be present, a steady waste of the tissue-proteins goes on.
If non-nitrogenous food in the form of sugar is supplied to an other-
wise starving animal, the premortal rise in the nitrogen excretion
does not occur. By giving a sufficient quantity of sugar, or df
sugar and fat, but practically no protein (so-called nitrogen starva-
tion), the excretion of nitrogen may be reduced to one-third of its
amount when no food at all is given. This is true both in animals
* If the animal has been for some time on a diet containing an abundance
of proteins, several days may elapse before the constant excretion of urea
is reached; if the previous diet has been poor in protein, the constant star-
vation output may be at once established.
604 METABOLISM, NUTRITION AND DIETETICS
and man. In this way the daily excretion of nitrogen in a man has
been reduced to 4 grammes. It is a remarkable fact that while a
mixture of carbo-hydrate and fat will act just as well as carbo-
hydrate alone in bringing about this reduction in the nitrogen
output, fat without carbo-hydrate is much less effective. The
hypothesis suggested by Landergren to explain this is alluded to
on another page (p. 551).
The results obtained on fasting men differ in some respects from
those obtained on starving animals. In ten days of hunger, Cetti,
a professional ' fasting man ' of meagre habit, excreted 112 grammes
nitrogen, or an average of n grammes a day. The excretion was
least on the eighth, ninth, and tenth days — namely, about 9 grammes
a day. On the third day it was higher than on the second, and
almost as high on
the fourth as on the
third. A similar rise
in the nitrogen
excretion on the
second day has been
observed in other
fasting men, but is
either rare or absent
in fasting dogs. The
explanation appar-
_fl •_ ^al :„ tv.e Fig. 199.— Excretion of Urea in Starvation. A is a curv«
,ntiy 1 nai in me representing the quantity of urea excreted daily by a
ordinary tOOd OI fat dog in a starvation period of sixty days. B is the
man there is a curve of urea excretion in a lean young dog in a
cn-Aafpr ahiinrlanrp starvation period of twenty-four days. Both are con-
structed from Falck's numbers, but in A only every
Of car DO - hydrates third day js put m> in order to save space. The num.
and fats, the pro- bers along the vertical axis represent grammes of urea;
tein - sparing action those along the aorizontal axis davs flom the beginning
,5 , ? of starvation,
of which is most
pronounced at the very beginning of the starvation period. The
quantity of chlorine and alkalies in the urine was also diminished,
while the phenol was increased. The respiratory quotient sank to
0-66 to 0-69 — even less than the quotient corresponding to oxida-
tion of fats alone. The meaning of this, in all probability, is that
some of the carbon of the broken-down proteins was laid up in the
body as glycogen (Zuntz). In another professional fasting man
(Succi) with a considerable amount of body-fat, the excretion of
nitrogen was found to diminish continuously during a fast of thirty
days, being less than 7 grammes on the tenth day. In another fast
of twenty-one days by the same person it was a little less than
3 grammes on the last day. The surprisingly small nitrogenous
waste in this case is perhaps to be accounted for by the protein-
sparing action of the abundant body-fat. The nitrogenous metabo-
STATISTICS OF NUTRITION
605
lism has also been investigated during long-continued hypnotic sleep
(Hoover and Sollmann). The results were very much the same as
in an ordinary starvation experiment.
It might be supposed that' if an animal was given as much nitrogen
in the food in the form of proteins as corresponded to its daily loss
of nitrogen during starvation, this loss would be entirely prevented
and nitrogenous equilibrium restored. The supposition would be
very far from the reality. If a dog of 30 kilos weight, which on
the tenth day of starvation excreted 11-4 grammes urea, had then
received a daily quantity of protein equivalent to this amount —
that is to say, about 34 grammes of dry protein, or 175 grammes of
lean meat — the excretion of nitrogen would at once have leaped
up to nearly double its starvation value. If the quantity of protein
in the diet was progressively increased, the output of urea would
increase along with it, but at an ever- slackening rate; and at length
a condition would be reached in which the income of nitrogen
exactly balanced the expenditure, and the animal neither lost nor
gained flesh.
In an experiment of Volt's, for instance, the calculated loss of flesh
in a dog with no food at all was 190 grammes a day. The animal was
now fed on a gradually increasing diet of lean meat, with the following
result :
Flesh in the
Food.
Flesh used up in
the Body.
Net Loss oi
Body -flesh.
O
IQO
190
250
341
91
350
4II
61
4OO
454
54
450
471
21
480
492
12
The loss of nitrogen in the urine and faeces is what was measured.
Knowing the average composition of ' body-flesh ' (muscles, glands,
etc.), it is possible to translate results stated in terms of nitrogen into
results stated in terms of ' flesh.' Muscle contains approximately
3-4 per cent, of nitrogen. Here, with a diet of 480 grammes of meat, the
dog was still losing a little flesh; it would probably have required from
500 to 600 grammes for equilibrium. The results are graphically
represented in Fig. 200, p. 607.
The quantity of protein food necessary for nitrogenous equili-
brium varies with the condition of the organism ; an emaciated body
requires less than a muscular and well-nourished body. The least
quantity which would suffice to maintain in nitrogenous equilibrium
the famous 35 kilo dog of Voit, even in very meagre condition, was
480 grammes of lean meat, corresponding to 16 grammes of nitrogen,
or 35 grammes of urea — that is, about three times the daily loss
606 METABOLISM, NUTRITION AND DIETETICS
during starvation. From this lower limit up to 2,500 grammes oi
meat a day nitrogenous equilibrium could always be attained, the
animal putting on some flesh at each increase of diet, until at length
the whole 2,500 grammes was regularly 'used up in the twenty- four
hours. A further increase was only checked by digestive troubles.
A man, or at least a civilized man, can consume a much smaller
amount both absolutely and in proportion to the body- weight.
Rubner, with a body-weight of 72 kilos, was able to digest and absorb
over 1,400 grammes of lean meat; Ranke, with about the same
body-weight, could only use up 1,300 grammes on the first day of
his experiment, and less than 1,000 grammes on the third. But
whether the surplus of protein food above the necessary minimum
is great or small, nitrogen equilibrium is eventually attained, and
thereafter all the nitrogen of the food regularly appears in the
excreta; the explanation of this fact will be considered a little
later (p. 609).
So much for a purely protein diet. When fat is given in addition
to protein, nitrogenous equilibrium is attained with a smaller quantity
of the latter. A dog which, with protein food alone, is putting on
flesh, will put on more of it before nitrogenous equilibrium is reached
if a considerable quantity of fat be added to its diet. Fat, therefore,
economizes protein to a certain extent, as we have already recog-
nized in the case of the starving animal. On the other hand, when
protein is given in large quantities to a fat animal, the consumption
of fat is increased ; and if the food contains little or none, the body-
fat will diminish, while at the same time ' flesh ' may be put on.
The Banting cure for corpulence consists in putting the patient
upon a diet containing much protein, but little fat or carbo-hydrate ;
and the fact just mentioned throws light upon its action.
All that we have here said of fat is true of carbo-hydrates. To a
great extent these two kinds of food substances are complementary.
Carbo-hydrates economize proteins as fat does, but to a greater
extent, so that with an abundant supply of carbo-hydrate in the
food the minimum protein requirement can be forced down much
below what is possible on a diet of protein and fat alone. Carbo-
hydrates also economize fat, so that when a sufficient quantity of
starch or sugar is given to an otherwise starving animal, all loss of
carbon from the body, except that which goes off in the urea, krea-
tinin, etc., still excreted, can be prevented. Of course, the animal
ultimately dies, because the continuous, though diminished, loss of
protein cannot be made good. The fact that carbo-hydrates econo-
mize proteins so much more efficiently than fat indicates that sugar
is essential in the bodily metabolism, so that when carbo-hydrates
are absent from the food some of the protein must be broken down
so as to yield eventually the compounds necessary for the formation
of carbo-hydrate. It is probable, indeed, that purified proteins,
STATISTICS OF NUTRITION
607
vfOO
4.00
200
!OO
0 100 1$0
absolutely free from admixture with carbo-hydrates, which, of
course, is not the case with the natural protein foods, will not per-
manently suffice for nutrition, but that the protein must be supple-
mented by a certain amount of carbo-
hydrate in some form available for the
tissues. It would appear, indeed, that
fats are not absolutely indispensable
either for maintenance or for growth.
White rats have been seen to grow nor-
mally over long periods with dietaries
devoid of fat ; for example, mixtures of the
purified protein edestin (from hemp seed)
or casein with starch, sugar, and ' protein-
free milk ' freed from fat by extraction
with ether (Osborne and Mendel). While
in these experiments the food might not
have been free from the so-called ' lipoids/
it has been demonstrated that an impor-
tant group of substances of this class, the
phosphatides, can be synthesized in the
body, the necessary phosphorus being ob-
tainable even from inorganic phosphates
(McCollom).
Relation between Nitrogen excreted and
the Quantity of Protein Food. — At this
point we may consider a little more
closely a phenomenon already alluded to,
and to which much discussion used to be
devoted by writers on metabolism. It
has been stated that within the limits of
nitrogenous equilibrium, which is the nor-
mal state of the healthy adult, the body
lives up to its income of nitrogen ; it lays
by nothing for the future. In the actual
pinch of starvation the organism, when
its behaviour is tested by a comparison
of the intake and excretion of nitrogen,
appears to have become suddenly econo-
mical. When a plentiful supply of protein
is presented to the starving body, it seeins,
judged by the same criterion, to pass at
once from extreme frugality to luxury.
Some flesh may be put on for a short time, some nitrogen may be
stored up ; but the excretion of nitrogen is soon adjusted to the new
scale of supply, and the protein income is apparently spent as freely
as it is received. These facts were usually summed up in the
Fig. 200. — Curves constructed
to illustrate Nitrogenous
Equilibrium (from an Ex-
periment of Voit's). The
loss of flesh in grammes is
laid off along the horizontal
axis. The income and
expenditure corresponding
to a given loss are laid off
(in grammes of ' flesh ')
along the vertical axis. The
continuous curve is the
curve of income ; the dotted
curve, of expenditure. With
no income at all the expen-
diture is 190 grammes;
with an income of 480
grammes the expenditure
is 492 and the loss 12
grammes. Nitrogenous
equilibrium is represented
as being reached with an
income of about 530
grammes; here the two
curves cut one another.
608 METABOLISM. NUTRITION AND DIETETICS
dictum, often dignified as a ' law ' of nitrogenous metabolism that :
Consumption of protein is largely determined by supply (Practical
Exercises, p. 720).
To explain this many hypotheses were invented. The famous theory
of Voit assumed that the food-protein after absorption (the so-called
' circulating-protein ') is carried to the tissues and taken up by the
cells, where the greater part of it, without being incorporated with the
protoplasm, is nevertheless acted upon, rendered unstable, shaken to
pieces, as it were, by the whirl of life (by the intracellular enzymes we
might now say less dramatically) in the organized framework, the
interstices of which it fills.
Pniiger, on the other hand, maintained that we have no right to
draw a distinction between the consumption of organ- and circulating-
protein; that the whole of the latter ultimately rises to the height of
organ- or tissue -protein, and passes on to the downward stage of
metabolism only through the topmost step of organization. An increase
in the supply of nitrogenous material in the blood must, on this view,
be accompanied with an increased tendency to the break-up, the dis-
sociation, as Pfliiger put it, of the living substance. The actual organ-
ized elements, however, the existing cells, were not supposed to be
destroyed ; the building remained, for although stones were constantly
crumbling in its walls, others were being constantly built in.
A much less plausible view was that the tissue elements themselves are
short-lived ; that the old cells disappear bodily and are replaced by new
cells; and that the whole of the proteins of the food take part in this
process of total ruin and reconstruction. Histo logical evidence, as soon
as the methods of examining tissues with the microscope became
sufficiently refined, told strongly against this idea. Although the cells
of certain glands, such as the mammary, perhaps the mucous glands,
and especially the sebaceous glands (p. 565), exhibit changes which,
hastily interpreted, might seem to indicate that they break down
bodily, as an incident of functional activity, no proof could be obtained
of the production of new cells on the immense scale which this theory
would require. The relatively small and constant amount of the
endogenous metabolism indicates that the actual protoplasmic sub-
stance, the living framework of the cell, is comparatively stable;
that it does not break down rapidly; and that only a small and
fairly constant amount of food- or circulating-protein, or of the
decomposition products of protein, is required to supply the waste
of the organ -protein.
We have referred to these theories because there could scarcely be a
more instructive instance of the way in which theories become obsolete
with the advance of knowledge and of the way in which, with the
advance of knowledge, a phenomenon which appears an absolute riddle
to one generation may become fairly intelligible to the next, perhaps
childishly simple to a third. The student will not derive much benefit
from the perusal of this page should he fail to recognize that the
hypotheses of the twentieth century are mortal too, and bound for the
same bourne as those of the nineteenth.
It is apparent in the first place from our study of the metabolism
of the proteins that the conclusion, ' consumption of protein is pro-
portional to supply,' cannot be drawn from the equality of nitrogen
intake and nitrogen output. The amino-acids derived from proteins,
except that relatively small fraction employed in repairing the
STATISTICS OF NUTRITION
609
waste of the tissues, which in nitrogen equilibrium is exactly com-
pensated for by a corresponding release of amino-acids or their
equivalent from the cell-proteins, are indeed speedily deaminated
and the nitrogen of the amino-groups excreted as urea (with
ammonia compounds and creatinin). But, as we have seen, only a
small proportion of the chemical energy of the amino-acids and only
a small fraction of their carbon are liberated in this process. The
carbon-containing residues are katabolized only to the extent re-
quired by the momentary needs of the tissues, any balance being
stored as part of the reserve of carbo-hydrate or of fat. The body
does not possess the means of storing surplus amino-acids as such
or even in the form of proteins, except to the small extent corre-
sponding to any increase which may occur in the body-protein
when the food-protein is increased beyond the minimum required
for nitrogen equilibrium. Why the organism has not developed
the capacity to store large quantities of protein is, of course, an
interesting question, but it need scarcely be discussed here. One
obvious reason is that protein is not a suitable source, nor are amino-
acids apparently a suitable source of energy for the tissues until
they have been deaminated and have probably undergone further
decomposition and transformation. Therefore they are decomposed
at once and their available residue stored, if it is in any case to be
stored, in the more available form of carbo-hydrate (or fat).
Where the food-proteins differ greatly from the body-proteins in
the proportions of the various amino-acids, there would be no object
in storing a great surplus of those which are most" plentiful in the
food, if they were at the same time the scarcest in the tissues, or,
in the case of gland-cells, the scarcest in the proteins which they
manufacture for their secretions.
At any moment the magnitude of this non-utilizable surplus will
depend upon the quantity of that one of the indispensable amino-
acids which is present in the smallest amount. For the proper
proportion must be preserved between the different ' stones ' out of
which the molecule is built. When a single amino-acid is intro-
duced into the body, it is at once changed into urea and excreted,
since it cannot be utilized by itself for building up protein.
When the cells have once culled from the mixture circulating in
the blood the amino-acids, a full supply of which they have most
difficulty in obtaining, a residue, large or small, according to the
quantity and quality of the protein intake, will be left, and this can
only be utilized to supply energy or to add to the fat and carbo-
hydrate stores. For these uses removal of the amino-group is an
essential preliminary. The question whether the deamination of a
large part of the amino-acids coming from the intestine takes place
in the liver, so that the surplus nitrogen is shunted out of the main
metabolic current at its very source, has been already touched upon
39
6io METABOLISM, NUTRITION AND DIETETICS
(p. 588). Some writers conceive that in such a short-cut from pro-
tein to urea we have a kind of physiological safety-valve to protect
the tissues from the burden of an excessive metabolism. And il
by this is meant that it is advantageous to the tissues that a special
mechanism should exist to eliminate a surplus of nitrogen which they
do not require, and which they cannot store, and to present them
with a residue which they can utilize, the conception is certainly
correct. But there is no good evidence that in the presence of an
over-abundant supply of amino-acids the endogenous protein meta-
bolism would be essentially modified.
Relation of Nitrogenous Metabolism to Muscular Work. — This is
another of those classical physiological problems which it is difficult
to present properly apart from its historical setting. The general
result of much experimental work and long-continued discussion is
that when the work does not transgress what may be called ' normal
limits,' the excretion of nitrogen is nearly independent of mus-
cular work — that is to say, the quantity of nitrogen excreted by a
man on a given diet is practically the same whether he rests or works.
Before this was known it was maintained by Liebig that proteins
alone could supply the energy of muscular contraction — that, in
fact, proteins were solely used up in the nutrition and functional
activity of the nitrogenous tissues, while the non-protein food
yielded heat by its oxidation. As exact experiments multiplied, it
was found that muscular work, the production of which is the
function of by far the greatest mass of protein-containing tissue,
had little or no effect upon the excretion of urea in the urine. More
than this, it was shown that a certain amount of work accomplished
(by Pick and Wislicenus in climbing a mountain) on a non-nitrog-
enous diet had double the heat equivalent of the whole of the pro-
tein consumed in the body, as estimated by the urea excreted during,
and for a given time after, the work. On the assumption that all
the urea corresponding to the protein broken down was eliminated
during the time of this experiment, a part at least of the work must
have been derived from the energy of non-nitrogenous material.
And other experiments in which account was taken of the increase
in the carbon dioxide given off (as conspicuous an accompaniment
of muscular work as the constancy of the urea excretion), showed
that during muscular exertion carbonaceous substances other than
proteins — that is to say, fats and carbo-hydrates — are oxidized in
gi eater amount than during rest.
So the pendulum of physiological orthodoxy came full-swing to the
other side. Liebig and his school had taught that proteins alone were
consumed in functional activity; the majority of later physiologists
following Voit denied to the proteins any share whatever in the energy
which appears as muscular contraction. The proteins, they said,
1 repair the slow waste of the framework of the muscular machine,
replace a loose rivet, a worn-out belt, as occasion may require ; the
STATISTICS OF NUTRITION 611
carbo-hydrates and fats are the fuel which feeds the furnaces of life,
the materal which, dead itself, is oxidized in the interstices of the
living substance, and yields the energy for its work.'
Now, it is a singular circumstance, and full of instruction for the
ingenuous student of science, that the facts which were supposed
absolutely to disprove the older theory, and- absolutely to establish its
more modern rival, are now seen to do neither the one thing nor the
other. The fact — and it is a fact — that the excretion of nitrogen is
but little affected by muscular contraction, does not prove that none
of the energy of muscular work comes from proteins; the fact that,
under certain conditions, some of the muscular energy must apparently
come from non-nitrogenous materials, does not prove that these are the
normal source of it all. The distinction had again been made too
absolute. The pendulum must again swing back a little; and the
experiments of Pfliiger and his pupils were soon to set it moving.
In the first place, it is not perfectly correct to say that work
causes no increase in the excretion of nitrogen; excessive work in
man, and work, severe but not excessive, in a flesh- fed dog (Pfliiger),
do cause somewhat more nitrogen to be given off. On the first day
of work the increase is always much less than on the second and third ;
and on the first and second rest days, following work, the elimina-
tion of nitrogen is still increased. After excessive exercise in man
not only is the urea increased, but also the ammonia, kreatinin, and
if the subject is in poor training, the uric acid and purin bases (Paton,
Stockman, etc.). Moderate exercise causes no increase on the first
day, but a slight increase on the second. The meaning of these
facts seems to be that during muscular work the intensity of which
does not exceed certain limits, the protein waste of the muscular
substance itself is no greater than during rest. When, however, the
machine is ' speeded up ' beyond a certain point the wear and tear
is sensibly increased and an excess of tissue-protein is katabolized.
There is no reason to suppose that the tissue-protein thus broken
down will not yield energy for the muscular work by the oxidation
of its non-nitrogenous residue, just as well as the surplus amino-
bodies derived from food-protein. The muscular machine has the
peculiarity that it is constructed of combustible material ; even the
dust and the splinters, if we may so express it, which represent the
wear and tear of the machine can be burnt in the furnace which keeps
it going.
In the second place, even if the excretion of nitrogen were entirely
unaffected by work, this would not prove that none of the
energy of the work comes from proteins. For, as we have seen,
it is after the nitrogen has been split off and converted into urea
that the energy of a great part of the food-protein is developed by
oxidation. Further, since the animal body is a beautifully-balanced
mechanism which constantly adapts itself to its conditions, it is
conceivable that it may, when called upon to labour, save proteins
from lower uses to devote them to muscular contraction. In this
612 METABOLISM. NUTRITION AND DIETETICS
case the excretion of nitrogen would not necessarily be altered ; the
proteins which, in the absence of work, would have been oxidized
within the muscular substance or elsewhere, their energy appearing
entirely as heat, may, when the call for protein to take the place of
that broken down in muscular contraction arises, be diverted to this
purpose.
In any case, there is no doubt that a dog fed on lean meat may
go on for a long time performing far more work than can be yielded
by the energy of fat and carbo-hydrates occurring in traces in the
food, or taken from the stock in the animal's body at the beginning
of the period at work. A large portion, and perhaps the whole, of
the work, must in this case be derived from the energy of the pro-
teins (Pfliiger). On the other hand, it is well established that when
fats and carbo-hydrates are present in sufficient quantity in the
tissues or the food, they constitute the main source of the energy
of muscular contraction (p. 772), and there is some evidence that of
the two classes of food materials carbo-hydrates in the form of
dextrose (or glycogen) is the material of election.
The outcome, then, of this famous controversy is essentially a
compromise. Everybody now admits that the muscular machine
can and does utilize predominantly any one of the great groups
of food substances, be it carbo-hydrate, fat, or protein, when the
dietetic conditions are such that only one of these is offered to it
in large amount, the others being either absent or offered in small
amount. To be sure, amino-acids are not the first choice, but if
it must do so the muscle can make shift with them, and can indeed
make them serve excellently well. When all the food substances
are present in abundance, carbo-hydrate is favoured above fat, and
fat above protein.
Experience has shown that the minimum quantity of nitrogen
required in the food of a man whose daily work involves hard
physical toil is higher than the minimum required by a person lead-
ing an easy, sedentary life. This is evidently in accordance with
the view that protein is actually used up in muscular contraction ;
but it is not inconsistent with the opposite view. For the body of a
man fit for continuous hard labour has a greater mass of muscle
to feed than the body of a man who is only fit to handle a composing-
stick, or drive a quill, or ply a needle ; and the greater the muscular
mass, the greater the muscular waste. But if an animal just in
nitrogenous equilibrium on a diet of lean meat when doing no work
is made to labour day after day, it will lose flesh unless the diet
be increased. This must mean that some of the protein is being
diverted to muscular work, and that the balance is not sufficient
to keep up the original mass of ' flesh ' (see p. 628).
Relative Value of Different Proteins in Nutrition — Synthesis of
Amino-Acids. — The fact that the various proteins differ quantita-
STATISTICS OF NUTRITION 613
tively and qualitatively in respect to their amino-acids raises the ques-
tion of the relative value of different proteins in nutrition. In this is
involved the further question, whether the body can itself synthesize
from other materials any of the amino-acids which may be deficient,
or change one amino-acid into another. That the ' peptones ' derived
from a protein which is itself capable of permanently supplying
the whole nitrogenous intake of the organism can be substituted
for the protein scarcely needs demonstration, since it is known that
the protein is converted into peptones in digestion. Nevertheless,
this has been proved conclusively by feeding experiments with
peptones. It was to be expected, too, leaving out of account all
consideration of the means of overcoming the repugnance of animals
to accepting such unnatural food substances, that the further
products of protein hydrolysis, the amino-acids, etc., could be
substituted for the original proteins when these were themselves
adequate. For it is in the form of amino-acids or at most of such
relatively simple polypeptide groups as may still hang together
after complete digestion and absorption, that the nitrogenous food
substances are normally offered to the tissues. Experimental
demonstration of the feasibility of this substitution has also been
obtained. The split products of meat, for example, will keep an
animal in nitrogen equilibrium as well as the meat from which they
are derived. But what happens when one or more of the amino-
acids found in the proteins of the body are missing from the protein
of the food ? That the components of an amino-acid like arginin
(ornithin and urea), into which it can be split not only by the
possibly crude and violent methods of the chemical laboratory, but
also by the delicate and precisely-adapted ' biological ' action of a
special enzyme (arginase), should be able to replace the original
amino-acid is a fact which does not greatly help towards an answer.
For when these components, or ornithin alone, since urea is always
present in the body, are given instead of arginin, the reversal of the
enzyme reaction by which arginin is decomposed is all that is neces-
sary for its synthesis, and the reversal of such a reaction is doubtless
a very commonplace affair in tissue metabolism. The formation
of one amino-acid from another, or from materials which do not
originate exclusively from protein, is a different thing, and the
answer to the question raised, so far as it can yet be given, is that
the way in which the body deals with a deficiency in the protein
' building stones ' depends upon the nature of the missing amino-
acids. Thus, the phospho-protein casein does not yield glycin on
hydrolysis; yet it has been shown that casein is a perfectly adequate
or complete protein food capable of covering the whole nitrogen
requirement of the body over long periods. The same is true of the
cleavage products of casein which has been subjected to pancreatic
digestion. In an animal fed on no other protein than casein, with
614 METABOLISM, NUTRITION AND DIETETICS
suitable quantities of carbo-hydrate and fat in addition, the glycin
contained in certain of the body proteins must therefore have been
produced in the body itself. We have already- seen (p. 580) that
for the synthesis of hippuric acid after the administration of benzoic
acid, glycin is necessary, and the quantity of hippuric acid which
can be thus produced is so great that it is impossible to suppose
that it all comes from glycin preformed in the body or from glycin
in the food substances. It may accordingly be taken as proved
that the tissues have the power of synthesizing at least this one of
the amino-acids (amino-acetic acid), reckoned among the protein
' building stones. ' It is said that if the casein has been hydrolysed
by acid, the products will not preserve nitrogen equilibrium, per-
haps because the acid has broken up all the polypeptides (p. 2),
some of which the cells may need as the starting-point of protein
synthesis. This, however, is uncertain.
Lysin also appears to be capable of being synthesized in the body,
and protein foods free from lysin, or containing only a trace of it,
may yet be adequate for nutrition and growth. Prolin, too, is not
indispensable, and this is of special interest, for the amino-acids
hitherto mentioned as capable of being built up in the tissues are
all more or less directly related to each other, being derivatives of
the series of saturated fatty acids. The task of changing one of
these into another in which the food is deficient may, therefore, be
considered a comparatively easy one. But prolin has no obvious
relation to most of the other amino-acids.
It is a-pyrrolidin carboxylic acid,
CHg — CHj CH2 — CHg
CH8 CH.COOH— i.e., pyrrolidin, CH2 CH2
NH NH
in which H in one of the CH2 groups is replaced by carboxyi (COOH) .
It has been suggested that prolin may be formed in the body from
glutaminic (amino-glutaric) acid, which by loss of a molecule of water
can be made to yield a-pyrrolidon carboxylic acid. Thus,
CH8.CH2.CH.COOH CH2— CHt
COOH NH2 -H2O = CO CH.COOH
NH
Glutaminic acid. a-pyrrolidon carboxylic acid.
By reduction the latter compound might be changed into prolin.
With proteins deficient in certain other amino-acids a totally
different result has been obtained. Gelatin, for example, contains
most of the amino-acids and other groups which compose the body
proteins, but tyrosin, cystin, 'and tryptopha*ne are lacking in the
STATISTICS OF NUTRITION 615
gelatin molecule. Zein, an alcohol-soluble protein or prolamin*
derived from maize, yields no tryptophane, glycin, or lysin. Now,
it is found that neither gelatin nor zein can replace the whole of
the ordinary proteins in the food. When only enough protein is
taken to prevent loss of nitrogen from the body, one-fifth of the
necessary nitrogen can be supplied in the form of gelatin. When
the food is much richer than this in ordinary protein, a correspond-
ingly greater proportion of the protein can be replaced by gelatin.
The surplus is not used in the endogenous metabolism of the cells
(p. 573), but supplies energy to the body after the elimination of
its nitrogen as urea, just as the surplus protein would do. Thus
gelatin economizes protein in the same way that fat and carbo-
hydrates do, but also to some extent in a different way by supplying
' building stones ' for the protoplasm. It is therefore an interesting
question whether gelatin can fully replace protein when the missing
substances are given in addition. Kauffmann has stated that his
own nitrogen requirement (15 -2 grammes) was almost completely
covered by a mixture containing 93 per cent, of the nitrogen in the
form of gelatin, 4 per cent, as tyrosin, 2 per cent, as cystin, and
i per cent, as tryptophane, in addition to the same amounts of
carbo-hydrate and fatty food as in the comparison diet, in which
the nitrogen was supplied in the form of plasmon, a commercial
preparation of casein.
Similar results have been reported in experiments on animals in
which attempts have been made to ' complete ' such inadequate
proteins by addition of the missing amino-bodies, with fair but,
according to Osborne and Mendel, not entirely satisfactory results.
The converse experiment, in which an amino-acid such as trypto-
phane has been purposely eliminated from the food mixture, has
also been tried, with the result that rapid deterioration in the
condition of the animal ensued. It would seem, indeed, that
whatever capacity the animal body may have for synthesizing
certain of the amino-acids, this power does not extend to the cyclic
compounds tryptophane, tyrosin, phenylalanin, and histidin, which
must be supplied in the food. It has been suggested by Osborne
that in this regard an essential difference exists between the animal
and the plant, the latter alone being endowed with the function of
' cyclopoiesis,' or formation of substances of the cyclic type. It
is not clearly understood as yet on what this difference really hinges,
whether, as some have supposed, on the inability of the animal
organism to form the appropriate fatty acid radicals, or on some
* The prolamins are so called because on hydrolysis they yield exceptionally
large amounts of prolin (p. 360) and ammonia. They are insoluble in water
and absolute alcohol, but soluble in 70 to 80 per cent, alcohol and in dilute
acids and alkalies. Besides zein they include gliadin (from wheat and rye),
hordein (from barley), and bynin (from malt). They are extraordinarily rich
in glutaminic acid, hordein yielding more than any protein hitherto investi-
gated (over 41 per cent).
6ib METABOLISM, NUTRITION AND BIETETICS
other limitation of its chemical powers. While the cyclic (and hetero-
cyclic) compounds cannot be replaced by other ' Bausteine ' of the
proteins, they may to some extent replace each other. Thus it would
seem that tyrosin can be replaced by phenylalanin (Abderhalden) .
While some of the food proteins like casein are sufficient by
themselves to supply all the amino-bodies necessary not only for
the maintenance, but also for the growth of the body, and can
accordingly be termed adequate or complete protein food sub-
stances, others, like gelatin, are insufficient by themselves to supply
the protein required for mere maintenance, still less for growth,
Fig. 201. — Two Female Rats of the Same Age (140 days). The upper one was fed on
an ordinary diet, and is of the normal weight for its age. The lower one was
fed on a diet composed of a mixture of isolated food-stuffs. Its weight is only
equal to that of a normal rat thirty-six days old (Osborne and Mendel).
and may be spoken of as inadequate or incomplete proteins. There
is a third intermediate group, comprising proteins which suffice
when given as the sole protein food to maintain the body for an
indefinitely long period, and to repair the tissue waste without per-
mitting growth of the animal to take place. Gliadin and hordein
(see footnote, p. 615) are representatives of this group. The ex-
periments of Osborne and Mendel with gliadin are of special interest,
since this substance is very differently constituted from the ordinary
food proteins, as well as from the tissue proteins of the animal
body. While, as already stated, it yields very large quantities of
glutaminic acid, prolin, and ammonia, it either contains no lysin
STATISTICS OF NUTRITION 617
and no glycin, or yields too little to be detected with certainty.
It also yields comparatively little histidin and arginin. Now, it
has been found that a dietary containing carbo-hydrate in the form
of starch, fats in the form of lard, and inorganic salts, but no pro-
tein except gliadin* suffices to maintain adult rats in good condition
for very long periods (up to 290 days), and also to maintain young
rats in a stationary condition as regards growth, but in perfect
health. The youthful appearance of the rats whose growth was
thus inhibited was very striking, and corresponded with their size
rather than with their age. The capacity for growth on a normal
diet was apparently not in the least diminished; the growth pro-
cesses simply remained in abeyance.
' In one rat, after a continuous suppression of growth lasting 277 days,
when the animal was 314 days old — an age at which normally little or
no growth takes place — satisfactory growth was resumed on a suitable
diet.' A still more remarkable experiment was the following: ' A male
rat, kept for 154 days with gliadin as the sole protein in the food, was
paired with a female also on the gliadin diet. At the end of 178 days
on the gliadin diet she gave birth to four young, which were satisfactorily
nourished by the mother, still on gliadin, during the first month of
their existence. After a month three of the young rats were removed
from the mother and put on diets of casein food (i.e., casein plus suitable
proportions of carbo-hydrate, fat, and inorganic materials), edestin
food and milk food respectively. The fourth was left with the mother.
The fourth rat began to evince a failure to grow at about the period
(thirty days) when young rats are wont to depend upon extraneous
food.
The meaning of this last observation can only be that the young
animal, when obliged to depend upon its share of the gliadin food,
left with the mother in place of the milk formed by the mother
from this same gliadin food mixture, showed the typical failure to
grow on a diet inadequate as regards the power of producing growth
in respect to the protein contained in it. On the other hand, in the
body of the mother this inadequate diet had been so transformed
that not only had she maintained her body-weight and repaired
* Certain accessory substances of unknown nature, contained in some of
the natural foods must also be supplied (p. 632). Osborne and Mendel, for
instance, gave their animals a certain amount of ' protein-free milk,' contain-
ing the salts of milk, but only traces of milk proteins. The important thing
in the ' protein-free milk ' is neither the slight residue of protein nor the salt,
but an unknown substance, a so-called 'water-soluble vitamine.' When this
was supplied in the ' protein-free milk ' the animals were maintained on the
artificial diet for very long periods, although they did not grow. It has since
been rendered probable that in addition to the water-soluble vitamine, fat-
soluble vitamine (McCollom) is necessary for full growth of rats and the main-
tenance in health of the adults, upon otherwise complete artificial diets, for
a great part of their natural life-span. Such fat-soluble vitamines may be
supplied by replacing a part of the lard by butter-fat, egg-yolk fat, beef fat,
or codliver oil.
618 METABOLISM, NUTRITION AND DIETETICS
her tissue waste completely, but she had produced from it every-
thing necessary for the development of the embryo rats up to full
term, and after that everything necessary (in the form of milk)
for their normal growth during the period of suckling. On the
whole, a very large amount of body tissue in proportion to the
original weight of the mother must have been formed or renewed
in the 200 days or more during which the experiment continued,
and during which gliadin was being steadily transmuted into tissue
protein, and latterly into the proteins of milk as well, by what
might almost be called a feat of chemical legerdemain. There must
have occurred a synthesis ' not only of the Bausteine (the " building-
stones ") deficient in the protein intake, but likewise of tissue and
milk components like the nucleic acids (with their content of purins,
pyrimidins, and organically combined phosphorus) and phospho-
proteins like casein, etc., which were completely missing ' in the food.
It has been suggested that the bacteria of the alimentary canal,
which, of course, are plant cells, may have and may exercise on a large
scale the power of building up new amino-acids from a variety of
materials in the intestinal contents, and that they may thus be synthe-
sizing agents, thanks to which inadequate proteins may be reshaped to
proteins adequate to the needs of the body. It is precisely, however,
in the case of incomplete proteins like gelatin deficient in cyclical
compounds, that the body fails to effect the necessary transformation
in spite of the fact that plant cells are supposed to be specially capable
of forming these compounds. In any case bacterial action would not
explain why proteins like gliadin and hordein are only adequate for the
renewal of tissue, and not for its growth. This points rather to the
possibility that the processes by which the nitrogenous compounds
degraded in cellular metabolism are replaced are not of the same char-
acter as the processes by which new nitrogenous complexes are built
up into growing protoplasm. If, for instance, the protein molecule is
not completely disrupted in ordinary metabolism, it will not need to be
completely reconstructed, while in the formation of new tissue complete
protein molecules will have to be synthesized. Incomplete proteins
like gliadin may furnish building-stones adequate for repairing the
house, but inadequate for building it from the foundations.
Income and Expenditure of Carbon — The Carbon Balance-Sheet. —
This division of the subject has been .necessarily referred to in
treating of the nitrogen balance-sheet, and may now be formally
completed.
Carbon Equilibrium. — A body in nitrogenous equilibrium may or
may not be in carbon equilibrium. It has been repeatedly pointed
out that the continued loss or gain of carbon by an organism in
nitrogenous equilibrium means the loss or gain of fat ; and, since
the quantity of fat in the body may vary within wide limits without
harm, carbon equilibrium is less important than nitrogen equili-
brium. It is also less easily attained when the carbon of the food
is increased, for the consumption of fat is not necessarily increased
STATISTICS OF NUTRITION 619
with the supply of fat or fat-producing food, and there is by no
means the same prompt adjustment of expenditure to income in
the case of carbon as in the case of nitrogen.
Carbon equilibrium can be obtained in a flesh-eating animal, like
a dog, with an exclusively protein diet; but a far higher minimum
is required than for nitrogenous equilibrium alone. Voit's dog
required at least 1,500 grammes of meat in the twenty- four hours
to prevent his body from losing carbon. For a man weighing
70 kilos, the daily excretion of carbon on an ordinary diet is 250 to
300 grammes. About 2,000 grammes of lean meat would be re-
quired to yield this quantity of carbon; and, even if such a mass
could be digested and absorbed, more than three times the necessary
nitrogen would have to undergo preliminary cleavage and excretion
as urea or be thrown upon the tissues.
Not only may carbon equilibrium be maintained for a short time
in a dog on a diet containing fat only, or fat and carbo-hydrates, but
the expenditure of carbon may be less than the income, and fat may
be stored up. But, of course, if this diet is continued, the animal
ultimately dies of nitrogen starvation.
So far we have spoken only of the income and expenditure of
carbon and nitrogen; and from these data alone it is possible to
deduce many important facts in metabolism, since, knowing the
elementary composition of proteins, fats, and carbo-hydrates, we
can, on certain assumptions, translate into terms of proteins pr fat
the gain or loss of an organism in nitrogen and carbon, or in carbon
alone. But the hydrogen and oxygen contained in the solids and
water of the food, and the oxygen taken in by the lungs, are just as
important as the carbon and nitrogen; it is just as necessary to take
account of them in drawing up a complete and accurate balance-
sheet of nutrition. Fortunately, however, it is permissible to
devote much less time to them here, for when we have determined
the quantitative relations of the absorption and excretion of the
carbon and nitrogen, we have also to a large extent determined
those of the oxygen and hydrogen.
Income and Expenditure of Oxygen and Hydrogen. — The oxygen
absorbed as gas and in the solids of the food is given off chiefly as
carbon dioxide by the lungs; to a small extent as water by the lungs,
kidneys, and skin; and as urea and other substances in the urine
and faeces. The hydrogen of the solids of the food is excreted in
part as urea, but in far larger amount as water. The hydrogen and
oxygen of the ingested water pass off as water, without, so far as
we know, undergoing any chemical change, or existing in any other
form within the body. But it is important to recognize that
although none of the water taken in as such is broken up, some
water is manufactured in the tissues by the oxidation of hydrogen.
6ao METABOLISM, NUTRITION AND DIETETICS
We have already considered (p. 241) the gaseous exchange in the
lungs, and we have seen that all the oxygen taken in does not
reappear as carbon dioxide. It was stated there that the missing
oxygen goes to oxidize other elements than carbon, and especially
to oxidize hydrogen. We have now to explain more fully the cause
of this oxygen deficit
The Oxygen Deficit. — The carbo-hydrates contain in themselves
enough oxygen to form water with all their hydrogen ; they account for
a part of the water-formation in the body, but for none of the oxygen
deficit.
The fats are very different ; their hydrogen can be nothing like com-
pletely oxidized by their oxygen. A gramme of hydrogen is contained
in 8-5 grammes of dry fat, and needs 8 grammes of oxygen for its com-
plete combustion. Only i gramme of oxygen is yielded by the fat
itself; so that if a man uses 100 grammes of fat in twenty -four hours,
rather more than 80 grammes of the oxygen taken in must go to
oxidize the hydrogen of the fat.
The proteins also contribute to the deficit. In 100 grammes of
dry proteins there are 15 grammes of nitrogen, 7 grammes of hydrogen,
and 21 grammes of oxygen. The carbon does not concern us at present.
The 33 grammes of urea, corresponding to 100 grammes of protein,
contains 15 grammes of nitrogen, a little more than 2 grammes of
hydrogen, and a little less than 9 grammes of oxygen. There remain
5 grammes of hydrogen and 12 grammes of oxygen. But 5 grammes of
hydrogen needs for complete combustion 40 grammes of oxygen ; there-
fore 28 grammes of the oxygen taken in must go to oxidize the hydrogen
of 100 grammes of protein. Taking 140 grammes of protein as the
amount in a liberal diet for a man, we get 39 grammes as the required
quantity of oxygen. This, added to the 80 grammes needed for the
hydrogen of the fat, makes a total of, say, 120 grammes, equivalent to
about 85 litres of oxygen. A small amount of oxygen also goes to
oxidize the sulphur of proteins.
With a diet containing less fat and protein and more carbo-hydrate,
the oxygen deficit would of course be less.
The Production of Water in the Body.— One gramme of hydrogen
corresponds to 9 grammes of water. In 140 grammes of proteins and
100 grammes of fat there are, in round numbers, 22 grammes of hydro-
gen; in 350 grammes of starch, 21-5 grammes. With this diet,
43 '5 grammes of hydrogen is oxidized to water within the body in
twenty-four hours, corresponding to a water production of 391 grammes,
or 15 to 20 per cent, of the whole excretion of water. It has been
observed that during starvation the tissues sometimes become richer
in water, even when none is drunk. The only explanation is that the
elimination of water does not keep pace with the rate at which it is
produced from the hydrogen of the broken-down tissue-substances, or
set free from the solids with which it is (physically ?) united.
Inorganic Salts. — The inorganic salts of the excreta, like the
water, are for the most part derived from the salts of the food,
which do not in general undergo decomposition in the body. A
portion of the chlorides, however, is broken up to yield the hydro-
chloric acid of the gastric juice. Within the body some of the salts
STATISTICS OF NUTRITION 621
are more or less intimately united to the proteins of the tissues and
juices, some simply dissolved in the latter. The chlorides, phos-
phates and carbonates are the most important ; the potassium salts
belong especially to the organized tissue elements, the sodium salts
to the liquids of the body; calcium phosphate and carbonate pre-
dominate in the bones. The amount and composition of the ash
of each organ only change within narrow limits. In hunger the
organism clings to its inorganic materials, as it clings to its tissue-
proteins; the former are just as essential to life as the latter. In a
starving animal chlorine almost disappears from the urine at a time
when there is still much chlorine in the body; only the inorganic
salts which have been united to the used-up proteins are excreted,
so that a starving animal never dies for want of salts.
When sodium chloride is omitted as an addition to the food of
man, the decomposition of protein seems to be slightly accelerated,
but for a time, at least, there are no serious symptoms (Belli).
It is a general rule that purely carnivorous animals do not desire
salt, and the same is true of human beings living on a purely animal
diet, while vegetable feeders eagerly seek it. On the other hand,
when an animal, even a carnivore, is fed with a diet as far as possible
artificially freed from salts, but otherwise sufficient, it dies of salt-
hunger. The blood first loses inorganic material, then the organs.
The total loss is very small in proportion to the quantity still
retained in the body; but it is sufficient to cause the death of a
pigeon in three weeks, and of a dog in six, with marked symptoms
of muscular and nervous weakness. A deficiency of lime salts
causes changes particularly in the skeleton, although the nutrition
of the rest of the body is also interfered with. These changes are
of course most marked in young animals, in which the bones are
growing rapidly. In pigeons on a diet containing very little calcium
the bones of the skull and sternum become extremely thin and
riddled with holes, while the bones concerned in movement scarcely
suffer at all (E. Voit).
It is not indifferent in what form the calcium is taken, nor can it be
replaced to any great extent by other earthy bases, as magnesium or
strontium. Weiske fed five young rabbits of the same litter on oats,
a food relatively poor in calcium. One of the rabbits received in
addition calcium carbonate, another calcium sulphate, a third mag-
nesium carbonate, and a fourth strontium carbonate. At the end of a
certain time it was found that the skeleton of the rabbit fed with calcium
carbonate was the heaviest and strongest of all, and contained the
greatest proportion of mineral matter. Then came the rabbit fed with
calcium sulphate. The animal which received only oats had the worst-
developed skeleton; the condition of the animals fed with magnesium
and strontium carbonates was but little better.
Milk as a Food.— Milk is a food rich in calcium and also in phos-
phorus, a circumstance evidently related to the rapid development
622 METABOLISM, NUTRITION AND DIETETICS
of the skeleton in the young child. As in the other natural foods,
the calcium and phosphorus are partly in the form of organic com-
pounds, united with the proteins, the calcium especially with
caseinogen, and partly in the form of inorganic salts. Both of these
elements are more easily assimilated by the body in the organic
than in the inorganic form. The same is true of iron, which exists
in organic combination in the bran of wheat, in the haemoglobin of
the blood and of muscular fibres, in the nuclei of most cells, vegetable
and animal, and conspicuously in the nuclein compounds of the yolk
of the egg. Attempts have been made to increase the amount of
iron in hen's eggs by giving them food mixed with preparations of
iron — e.g., iron citrate. An increase takes place, but only after a
long time. Thus in one experiment 100 grammes of egg- substance
contained 4-4 milligrammes of Fe2O3 before the administration of
the iron was begun; after feeding with iron for three and a half
weeks the amount was 4-5 milligrammes, after more than two
months 7-4 milligrammes; and after a year only 7-3 milligrammes.
Although, as we have seen, inorganic iron can be absorbed, it is
certainly the case that under ordinary conditions all the iron that
the body receives or needs is taken in the form of organic com-
pounds, since there is no inorganic iron in the natural food sub-
stances. Stockman, from careful estimations of the quantity of iron
in a number of actual dietaries, finds that it only amounts to about
8 to 10 milligrammes a day. He concludes that the greater part of
it must be retained in the body and used over and over again.
Milk is poor in iron, but this does not hinder the development of
the young child, except when it is weaned too late, when it is apt to
become anaemic unless the milk is supplemented with a food rich
in iron, such as yolk of egg. The explanation is that the foetus,
especially in the last three months of intra-uterine life, accumulates
a store of iron in the liver and other organs; so that, in proportion
to its body-weight, it is at birth several times richer in iron than the
adult. This iron, of course, all comes from the mother, and the
loss is not exactly balanced by the excess of iron in her food ; certain
of her organs, the spleen, for instance, though not apparently the
liver, are impoverished as regards their content of iron.
.SECTION V. — DIETETICS.
There are two ways in which we can arrive at a knowledge of the
amount of the various food substances necessary for an average
man: (a) By considering the diet of large numbers of people doing
fairly definite work, and sufficiently, but not extravagantly, fed —
e.g., soldiers, gangs of navvies, or plantation labourers; (b) by making
special experiments on one or more individuals.
Voit, bringing together a large number of observations, concluded
DIETETICS 623
that an ' average workman/ weighing 70 to 75 kilos, and working
ten hours a day, required in the twenty-four hours 118 grammes
protein, 56 grammes fat, and 500 grammes carbo-hydrate, corre-
sponding to about 18-8 grammes* nitrogen, and at least 328 grammes
carbon.
Ranke found the following a sufficient diet for himself, with a
body- weight of 74 kilos :
Proteins - ... IOQ grammes.
Fat - 100
Carbo-hydrates - 240 ,,
This corresponds to only 16 grammes nitrogen and, say, 230 grammes
carbon.
A German soldier in the field receives on the average :
Proteins - - - - - 151 grammes.
Fat ... - 46
Carbo-hydrates - 522
representing about 24 grammes nitrogen and 340 grammes carbon.
The average ration for four British regiments in peace-time con-
tained 133 grammes protein, 115 grammes fat, and 424 grammes
carbo-hydrate ( = 3,400 calories). But in addition the soldiers
constantly obtained at their own expense a supper, generally com-
prising meat (Pembrey). The Russian army war ration in/ the
Manchurian campaign is said to have comprised 187 grammes
protein and 775 grammes carbo-hydrate, but only 27 grammes fat
( = 4,900 calories). The diet of certain miners (Steinheil) and lum-
berers (Liebig) contained respectively 133 and 112 grammes protein,
113 and 309 grammes fat, and 634 and 691 grammes carbo-hydrates.
The diet of a Japanese jinricksha man with a body- weight of
62 kilos contained 158 grammes protein, and its total heat value
was 5,050 calories. The work of these men in running long dis-
tances with passengers is very laborious. They consume large
amounts of fish, eggs, beef, and pork during their periods of rest,
and large quantities of rice during their working periods (McCay).
The diet of prize-fighters and of athletes in training is richer in
protein than any of these. The members of two college football
teams are stated to have consumed on the average 225 grammes
protein, 334 grammes fat, and 633 grammes carbo-hydrates
( = 6,800 calories). Caspari, from a study of the phenomena -of
training, concluded that continuous bodily work at a rate above
the ordinary requires a large amount of protein (2 to 3 grammes a
day per kilo of body- weight). But there seems to be a considerable
difference between different individuals. So that a definite and
typical diet for severe labour does not exist. And although perhaps
the hardest physical work ever done in the world is to break athletic
* Taking the percentage of nitrogen in protein at 16.
624 METABOLISM, NUTRITION AND DIETETICS
records, to cut and handle timber, to mine^coal, and to make war,
the diet on which these things are accomplished is very variable.
Recent observations tend to reduce the amount of protein con-
sidered necessary for a person under ordinary conditions. Siven
remained in nitrogen equilibrium, for a time at least, with an intake
of only 0-07 to 0-08 gramme of nitrogen (0-4 to 0-5 gramme of
protein) per kilo of body-weight, or not much more than one-third
of the amount in Ranke's diet. It is obvious that the endogenous
protein katabolism sets the limit below which it must be impossible
permanently to reduce the allowance of protein. But it would be
very hazardous to assume that this theoretical minimum limit
corresponds with the permissible physiological limit. From ex-
periments on men of various callings extending over many months,
Chittenden has concluded that the average man eats at least twice
as much protein as he really requires. We have already seen that
the amount of nitrogen required to repair the actual waste of the
tissues is comparatively small, and that with the ordinary amount
of protein in the food a very large fraction of the total nitrogen is
rapidly excreted as urea. There is no doubt, also, that many
persons consume too much protein, at any rate in the form of
animal food, and would feel better, work better, and probably live
longer, if they restricted themselves in this regard. But there is
no evidence that the digestion of such quantities of protein as the
average healthy man eats, or the elaboration and excretion of the
corresponding amounts of urea, ' strain ' in the least the digestive
apparatus, the liver, or the kidneys. And it may just as well be
argued that it is advantageous that much more than the minimum
protein requirement should be offered to the tissues, so that the
appropriate amino-acids, even the scarcest of them, may be sure
to be present in sufficient amount, rather than that the organs
should be subjected to the unnecessary ' strain ' of reconstructing
some of the amino-acids themselves, supposing that they possess
this power. In a question of this sort the immemorial experience
and instinct of mankind cannot be lightly waved aside.
McCay points out that while Bengalis in Lower Bengal subsist on
food containing only about one-third the amount of protein in such
a ' standard ' diet as Voit's (6 to 7 grammes of nitrogen a day), and
may therefore be supposed to be immune from the dangers of an
excessive protein metabolism, the large intake of carbo-hydrate
rendered necessar y by the poverty of the food in protein is associated
with perhaps g reater evils, among them a marked predisposition to
diabetes and renal troubles. Their weight, chest measurement, and
muscular development are inferior to those of other Asiatics living
in the same climate, but with dietetic habits or economic conditions
which ensure them a larger supply of protein. Thus the natives of
Behar, with a larger intake of nitrogen, derived from wheat, and the
natives of Eastern Bengal with a larger intake of nitrogen, derived
DIETETICS 625
from wheat and fish, are physically much superior to the rice-eating
Bengalis of Lower Bengal, although all belong to the same race.
If we decide the matter merely on physiological grounds, we may
say that for a man of 70 kilos, doing fairly hard, but not excessive,
work, 15 grammes nitrogen and 250 grammes carbon are a sufficient
allowance. The 15 grammes nitrogen will be contained in 95
grammes dry protein, which will also yield 50 grammes of the
required carbon. The balance of 200 grammes carbon could
theoretically ~ be supplied either in 450 grammes starch or in
260 grammes fat. But it has been found by experiment and by
experience (which is indeed a very complex and proverbially expen-
sive form of experiment) that for civilized man a mixture of these
is necessary for health, although the nomads of the Asian steppes,
and the herdsmen of the Pampas, are said to subsist for long periods
on flesh alone, and a dog can live very well on proteins* and fat.
The proportion of fat and carbo-hydrates in a diet may, however,
be varied within wide limits. Probably no ' work ' diet should
contain much less than 40 grammes of fat, but twice this amount
would be better; 80 grammes fat give about 60 grammes carbon,
so that from proteins and fat we have now got no grammes of the
necessary 250, leaving 140 grammes carbon to be taken in about
310 grammes starch, or an equivalent amount of cane-sugar or
dextrose. Adding 30 grammes inorganic salts, we can put down as
the solid portion of a normal diet sufficient from the physiological
point of view for a man of 70 kilos :
95 grammes proteins - - =T&, 2 s s
•a C ««
>>o S =
c« ^S S
1^
«-J8
S * 3 S g >
§S S5 ^ c
^ o^-°e
" ^So^
a*1*?
•§§ -3
rt r- <"
.: -5 M .5 w
S -3 N C -™
,
r* r-> *»^ *-* j *" "
ilssia^;
»-* « d » *S „ "C
l^lm1
?se«
W^P§
8) ** **
-el
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ADRENALS
663
the latent period of the secretion is so short that the reaction follows
the commencement of stimulation of the nerve after a time-interval
sensibly the same as when it is elicited by the corresponding amount
Fig. 213. — -20, Pocket Experiment with Stimulation of ^Right Splanchnic in Abdo-
men after Section of Both Splanchnics. 21, repetition of 20, but with a shorter
time of stimulation. The epinephrin rise of blood-pressure after 20 is consider-
ably greater than after 21. Time-trace, half-minutes (f reduction).
of adrenalin injected at the level of the adrenal veins. Even when
the glands have ceased to respond to stimulation of the nerves,
epinephrin can still be liberated into the blood by massaging the
glands with the fingers (Fig. 214).
Fig. 214. — Showing the Effect of Massage in Liberating Epinephrin from the Left
Adrenal whose Nerves had been Cut Five Weeks before. 27, cava pocket with
massage, the left adrenal vein being open to the pocket. 47 to 49, pocket with
massage, the left adrenal vein having been closed at 45 and opened at 48, after'
closure of the pocket. Massage begun at 45-A, stopped at 46. Blood-pressure
tracing from carotid artery. Time-trace, half-minutes (reduced to $).
A centre for epinephrin secretion seems to exist in the upper part
of the thoracic region of the spinal cord. After section of the cord
in the cervical region, even as low as the level of the last cervical
segment, the secretion persists, but it is abolished when the cord is
divided at the third or fourth dorsal segment.
064 INTERNAL SECRETION— ENDOCRINE GLANDS
The relation of the nervous system to the adrenal medulla has been
further illustrated by comparison of the amount of epinephrin which
can be extracted from the two adrenals when the nerves of one have been
cut. Under the influence of anaesthetics and some other drugs, bac-
terial toxins, such as diphtheria toxin, etc., the epinephrin store is
markedly diminished in the gland whose nerve supply has been left
intact as compared with the other.
For example, in a cat the fibres coming from the sympathetic to the
left semilunar ganglion, including the left splanchnic nerves, were cut,
and the animal allowed to recover. Several days later when it is known
that equality of epinephrin load in the two adrenals would have been
restored, morphin was administered to the animal, and after a few
hours it was killed, and the epinephrin in the adrenals assayed. The
left gland contained 0-28 milligramme, the right, o-ii milligramme. If
the animal had been suddenly killed without morphin, the two adrenals
would have been found to contain equal amounts of epinephrin. There-
fore the deficiency in the right gland must have been due to the fact
that it was not protected by section of its nerves.
A similar deficiency has been found in the unprotected gland aftei
administration of a drug, /3-tetrahydronaphthylamine, after surgical
operations (post-operative deficiency), and in many other conditions.
When the animal recovers the deficiency is gradually made good, the
adrenal having the power of forming and storing epinephrin up to a
ce "tain point in the absence of its nerve supply, although it is unable
to liberate it into the blood.
There is no foundation for the statement that emotional disturb-
ances, as fright or anger, cause a depletion of the epinephrin store of the
adrenals.
Summary : — The existence of a nervous mechanism through which
the gland is stimulated to secrete epinephrin into the blood can there-
fore be considered as definitely established. It is the function of the
epinephrin, once it has entered the circulation that is involved in doubt.
Although it is highly improbable that the concentrations necessary for
direct stimulation of sympathetic endings ever exist in the general mass
of the blood, it is quite possible that a ' sensitizing ' influence is exerted
by epinephrin upon the sympathetic peripheral mechanisms which
renders them more susceptible to nerve impulses originating in other
ways. The possibility of a more direct action of epinephrin upon the
chemistry of carbo-hydrate metabolism, particularly upon glycogenolvsis
or even upon glycogen formation has been emphasized by some writers.
But glycogen can be formed abundantly, and certain experimental
hyperglyccemias which depend upon the rapid transformation of
glycogen into dextrose can be produced after the epinephrin secretion
of the adrenals has been abolished.
Chemistry and Formation of Adrenalin. — It has been shown (Stolz,
Dakin) that adrenalin (C9H33NO3) is a dioxyphenyl-ethanol-methy
lamin,
CH
OH.C/\C.CH(OH).CH2NH.CH,
OH.C\/CH
CH
ADRENALS 665
It has been prepared synthetically, and in the body appears to be
formed, probably by the introduction of a methyl (CH3) group, from
a compound arising from an aromatic amino-acid (tyrosin or phenyl-
alanin). While the natural adrenalin rotates the plane of polarization
to the left, the artificial substance is optically inactive. This is because
it consists of equal parts of laevo-rotatory and dextro-rotatory adrenalin.
The artificial adrenalin has approximately half the effect of the natural
on the blood-pressure, from which it may be inferred that the dextro-
rotatory isomer has only a very slight pressor effect. The left and right
rotatory moieties have been separated. The former has exactly the
same power of raising the blood-pressure as the natural adrenalin, the
latter only ^ to -^s as much. Practically the same proportion holds
when the power of the two isomers in producing glycosuria is compared.
This constitutes important corroboration of the view already referred
to (p. 550), that adrenalin glycosuria is caused by an action on the
sympathetic system, for the effect on the blood-pressure is known
to be thus produced (Cushny).
It is in the medulla of the adrenals that the epinephrin is formed.
The medullary cells contain a substance which gives a yellow or brown
stain with chromic acid or chromates, and for this reason the cells are
called chromaffin or chromaphil. Similar cells are found elsewhere in
the body — e.g., within the sympathetic ganglia, and also strung out
in clumps along the course of the abdominal aorta below the level of
the adrenal glands (Vincent). These outlying masses of chromaffin
tissue appear to contain epinephrin, or a substance with similar physio-
logical actions, so that the formation of this compound seems to be a
property common to chromaphil tissue, no matter what its situation
may be. A remarkable fact, and one calculated to induce caution
in assigning a physiological function to epinephrin, is that the so-called
parotid gland of a Jamaican toad secretes it in a concentration not
much short of 5 per cent. (Abel).
Function of the Adrenal Cortex. — The function of the cortical cells is
obscure, but there is evidence that they, and not the chromaffin cells
of the medulla, are concerned in the production of the internal secretion,
whatever its nature may be, the loss of which leads so speedily to death
on removal of the adrenals. For example, the period of survival after
this operation is practically unaffected by the continuous intravenous
administration of adrenalin, although the loss of the medulla- might
be supposed to be compensated in this way. Still more convincing
is the fact already referred to that after removal of one adrenal and
denervation of the other in cats, epinephrin ceas>es to be discharged
in detectable amount, and yet the animal survives in good health. In
Addison's disease adrenalin is likewise powerless.
The weakness (asthenia) of the skeletal, and to some extent of the
cardiac, musculature which is characteristic of Addison:s disease, is
produced experimentally within a few hours by ligation of both adrenals,
and all the evidence goes to show that it is the cortical and not the
mediillary region which is related to this disease. When the adrenals
are not completely extirpated, compensatory hypertrophy of the re-
maining portions may occur, and the animal survive indefinitely. In
such cases it has been found that the hypertrophy is confined to the
cortex.
In animals like the rabbit in which accessory adrenals are not un-
common, when these are present complete removal of both adrenals
does not cause death. Now, the accessory adrenals consist of cortical
substance without medulla. Portions of the adrenal are readily
grafted under the skin, but only the cortex survives and grows.
666 INTERNAL SECRETION— ENDOCRINE GLANDS
The functional difference between cortex and medulla is easily under-
stood when we reflect that the morphological history of the two tissues
is quite different. The medulla is developed from cells which push
their way into the gla id from the rudiments of the sympathetic ganglia
at that level, and is therefore of ectodermic origin. The cortex is
derived from the same mesodermic structure which gives rise to the
kidneys and genital organs.
Embryologically, the cortical cells are related to the interstitial cells
of the ovaries and of the testes, and like these are characterized by their
richness in lipins (or lipoids). There is some evidence of an inter-
relation between the thyroid and all these groups of sex cells (interstitial
cells of ovary and testes, cortex of adrenal). Removal of a large part
of the adrenals in the rabbit causes slight though definite hypertrophy
of the thyroid and lymphoid hyperplasia. This is also seen in
Addison's disease in man.
Pituitary Body or Hypophysis. — In the pituitary body two parts
essentially different in origin and function may be distinguished:
(1) The large anterior lobe, or pars anterior, consisting of epithelial
cells, many of which are filled with granules of the type seen in
glandular epithelium, and abundantly provided with bloodvessels;
(2) the smaller posterior or nervous lobe, or pars nervosa, also
called the infundibular portion, consisting chiefly of neuroglia, the
whole connected with the floor of the third ventricle by a stalk
called the infundibulum.
A further subdivision of the epithelial portion is made into the
anterior lobe proper and the pars intermedia or intermediate lobe, con-
sisting of epithelial cells, less granular and less richly supplied with
bloodvessels than those of the pars anterior. The pars intermedia
forms an epithelial investment of the pars nervosa, almost completely
surrounding it and throwing out offshoots of epithelial cells into its
substance, which is also invaded by colloid material secreted by the
cells of the intermediate lobe. The differences in the structure of the
anterior and posterior lobes of the pituitary body correspond to a
difference in their development. The anterior lobe is developed (in
man in the fourth week of intra-uterine life) from an ectodermal pouch
(Rathke's pouch), which is pushed up from the roof of the bucco-
pharyngeal cavity towards the mid-brain. The posterior lobe is
developed from an extension of the neural ectoderm, which grows back-
wards as the infundibular process till it meets and blends with that
portion of the buccal pouch which gives rise to the pars intermedia.
The pars intermedia is separated from the anterior lobe proper by a
cleft which represents what is left of the lumen of Rathke's pouch.
In connection with the interpretation of the results of experiments on
removal of the pituitary body, it is of consequence to remember that
a residue of the same epithelium which develops into the anterior lobe
appears always to get cut off in the vault of the pharynx, constituting
the so-called pharyngeal hypophysis, and consisting of a cord of cells
identical with those of the anterior lobe (Haberfeld). Embryonic
' rests ' of hypophyseal tissue are also often found in the dura of the
sella turcica, in which the pituitary body lies, and in the body of the
sphenoid bone. Cells of the intermediate lobe also run up the stalk
of the infundibulum, and even stretch for a little distance along the
floor of the third ventricle. Add to this the formidable nature of the
ADRENALS 667
operations required for the extirpation of the hypophysis from its
sheltered position within the skull, and it will not be wondered at that
complete harmony has not been attained as to the consequences of its
removal. The best evidence at present is to the following effect:
When the pituitary body is completely removed, death speedily
and invariably ensues, in dogs, on the average within twenty-four
to forty-eight hours. Puppies often live as long as two or three
weeks. The much longer periods of survival occasionally witnessed
are due to failure to remove some small portion of the hypophyseal
epithelium. On the day after the operation the animals may be
able to walk about, to eat and drink, and may show an interest in
their surroundings. The temperature, pulse, and respiration at
this time may be normal. Soon, however, they become lethargic,
then comatose, with characteristically incurved spine, slow respira-
tion, with long-drawn inspiration, a feeble pulse, perfectly limp
muscles, and often a subnormal temperature, and the appearance
of sugar in the urine. This deep coma passes into death, with no
perceptible transition, and without a struggle (Paulesco, Gushing).
The ablation of a part of the cortical substance of the anterior
(epithelial) lobe of the hypophysis is compatible with permanent
survival, and gives rise to no symptom of disorder. The same is
true when only the posterior lobe is removed. This does not seem
to be followed by any recognizable symptoms. In some animals,
however, kept tinder observation for long periods after partial
removal of the anterior lobe, a marked tendency to accumulate
fat has been noted, accompanied by hypoplasia of the generative
organs in adults or the persistence of the infantile condition in
immature animals. On the other hand, complete removal of the
anterior lobe causes death, just as if the whole gland had been
taken away. Of all the structures included in the pituitary body,
the most important from the functional point of view appears to be
the superficial layer of the anterior lobe.
Mere separation of the stalk of the hypophysis may produce
effects sometimes as serious as those of total removal of the gland,
probably owing to the disturbance caused in the circulation. It is
stated, indeed, by some observers that the vulnerable point is the
base of the infundibulum, and that if this is not injured extirpation
of the hypophysis is not incompatible with continued existence,
and that in adult animals the resultant changes are only slight,
although much more pronounced, especially as regards the disturb-
ances in metabolism and development in young animals. It has
been asserted that the pituitary undergoes (compensatory ?) hyper-
trophy after thyroidectomy. Some observers have accordingly
assumed a similarity of function for these organs. It has even been
stated that the production of colloid material by the cells of the pars
intermedia is increased, and that colloid accumulates in the
668 INTERNAL SECRETION— ENDOCRINE GLANDS
nervous portion of the posterior lobe. But this colloid, whatever
its function may be, is very different from that of the thyroid
alveoli, for the (sheep's) pituitary contains no iodine after extir-
pation of the thyroid any more than before (Simpson and
Hunter). And in man pathological changes (tumours) in the
pituitary body are associated, not with myxcedema, or other
disease connected with changes in the thyroid, but frequently with
another condition, called acromegaly, in which the bones of the
limbs and face, especially the hands and feet and the lower jaw,
become hypertrophied.
Another condition often associated with tumours of the pituitary
is gigantism — a condition occurring before the normal growth of
the bones is completed, and resulting in a great increase in the
length of the bones both in the limbs and the trunk.
Action of Intravenous Injection of Extracts of the Pituitary. —
The effects on the vascular system of intravenous injection of
extracts of the pituitary gland are also very different from those
caused by thyroid extracts. The posterior lobe, or infundibular
body, including the pars intermedia, contains two active substances,
one pressor and the other depressor. The former is soluble in salt
solution, but insoluble in absolute alcohol and ether; while the
latter is soluble in salt solution as well as in alcohol and ether. The
pressor substance (obtained in fairly pure form in the preparation
called pituitrin, and in still greater concentration in a preparation
to which the name hypophysin has been given) causes a rise of
blood-pressure, due partly to constriction of the arterioles and
partly to an increase in the force of the heart-beat, both of which
are brought about by direct action. This rise of pressure lasts for
a considerable time, and is sometimes accompanied by a slowing
of the heart. A second dose injected before the effect of the first
has passed off is inactive ; and this distinguishes the pituitary from
the suprarenal extract. Associated with the pressor effect is an
increase in the flow of the urine. Whether this is due to a separate
diuretic substance, as some maintain, has not been definitely settled.
Indeed, the factors on which the diuretic action depends are
complex, and sometimes in spite of an increase of general arterial
pressure, and of the volume of the kidney, there is no increased flow of
urine. In diabetes insipidus pituitrin has been found to produce pre-
cisely the opposite effect — namely, diminution in the excessive urinary
flow. The pressor substance, unlike adrenalin, directly stimulates
smooth muscle fibres (especially the arteries, uterus, and spleen) irrespec-
tive of their innervation ^Dale).
Many other points of difference exist between the pressor principles
of the infundibular body and the adrenal medulla. For example,
pituitrin constricts the pupil and diminishes the flow of saliva from the
submaxillary gland, whereas adrenalin dilates the pupil and causes an
increased flow of saliva. Hypophysin and other preparations of the
posterior lobe have been employed to stimulate the uterine contractions
in obstetrical practice, but their use does not seem to be free from
ADRENALS
669
danger. . When injected intramuscularly, regular1 and powerful con-
tractions of the uterus are excited in two or three minutes at any stage
in parturition. Another effect of extracts of the infundibular body is
on the mammary gland. An increased flow of milk follows the injec-
Fig. 215. — Action of Extract of Infundibular Lobe (Pars Nervosa of Ox Pituitary).
P, Carotid pressure; K, kidney volume; U, drops of urine; S, signal showing point
at which pituitary extract was injected; T, time- trace in zo-second intervals.
T is also the zero of the blood-pressure (Hering).
tion of pituitrin (Simpson). But it is in doubt whether this is due to
increased secretion and not solely to stimulation of the smooth muscle
of the organ with expulsion of milk already formed. The depressor
substance produces a marked fall of blood-pressure, even when it is
injected during the rise of pressure caused by an injection of the pressor
Fig. 216. — Action of Extract of Hypophyseal Lobe of Pituitary on the Blood- Pressure
(W. W. Hamburger). The signal line at the top shows the time and length of
injection of the saline extract into the blood. Time-trace (at bottom) shows
second intervals. The figure is to be read from left to right.
substance. The anterior lobe, or hypophysis, also contains a depressor
substance. Intravenous injection of a saline extract causes a distinct
fall of blood-pressure, accompanied usually by acceleration and weaken-
ing of the heart (Fig. 216). A second injection immediately following
the first produces no change in the pressure (W. W. Hamburger) .
670
INTERNAL SECRETION— ENDOCRINE GLANDS
An active substance which has been termed ' tethelin,'* because of its
influence on growth, has been separated from the anterior lobe. On
intravenous injection into rabbits, it causes a slight fall of blood pres-
sure and rto diuresis. Its effects are therefore quite different from those
of the posterior lobe. Mixed with the food
f* /I"! /\ °^ m*ce' *t has Deen found to exert a charac-
'.' rJ / '* teristic influence upon their growth, retard-
ing it at certain stages, and accelerating it
at other stages (Robertson) .
It is not at present possible to deduce
from such clinical and experimental
observations as those described any co-
herent theory of the function of the
pituitary. That there is some connection
between the normal action of the gland,
and in particular of its Anterior lobe, and
the normal growth and nutrition of the
body, including the skeleton, is scarcely
to be doubted. The fact that administra-
tion of the dried gland substance to dogs
causes an increased excretion of calcium
on a diet rich in calcium is a further
indication of its influence on the meta-
bolism of bone (Malcolm). But so far
is the precise nature of this influence, if
it exists, from being fully understood,
that authorities of repute are still divided
on the question whether the symptoms
of acromegaly and gigantism are due to
atrophy or to hypertrophy of the active
3of
Fig. 217. — Action of Infundi-
bular Extract upon Virgin
Uterus of Guinea- Pig. The
same dose was applied three
times in succession to an iso-
lated segment, at the points
marked by the arrows at
the bottom of the curves.
After each application the
segment was washed with
Ringer's solution at R. The
tracings have been made to
overlap. (Reduced to one-
half.) (Dale.)
elements of the gland, to loss of its internal secretion, or to its
manufacture in excessive amount. There is evidence that the
colloid secretion of the posterior lobe, probably formed by the
epithelial cells of the pars intermedia, passes through the nervous
portion to enter the infundibulum and the third ventricle of the brain,
where it breaks down in the cerebro-spinal fluid (Hering). And
it has been suggested that in virtue of the action of the hormones
(p. 404) in this secretion on the vascular system in general, and on
the renal cells and the renal circulation in particular, the posterior
lobe constitutes a mechanism for the control of the secretion of urine.
But this suggestion is still in the realm of hypothesis. Some support
is given to it by the observation that continued irritation of the
posterior lobe by a plug of the gutta-percha compound used by
dentists for temporarily filling teeth introduced through the floer
of the sella turcica caused permanent polyuria in dogs, analogous
to the diabetes insipidus seen in man (Matthews).
* From T£0/;Xu>s, growing, nourishing.
67i
Pineal Gland. — Extracts of the pineal gland injected into the circula-
tion have no effect other than that due to the inorganic constituents
of the calcareous concretions or ' brain sand,' which are its character-
istic feature. Since in early life the organ has a glandular structure
which is later replaced by fibrous tissue, it has been supposed that it
may exercise some function in connection with growth. But so far
the physiology of the pineal body is practically a blank sheet, or, at
best, a budget of contradictory statements from which nothing certain
can be deduced. Thus in two of the most recent papers, each based
on a large number of careful experiments, one author concludes that
removal of the gland in male guinea-pigs is associated with hastened
development of the sexual organs, and in females with a tendency to
breed earlier than the normal controls (Horrax). The other observer
finds that feeding young guinea-pigs with pineal tissue from young
animals determines an earlier sexual maturity than normal, and in-
creases the rate of growth of the body (McCord) .
The alleged influence of the invasion of the gland in young children
by pathological growths in accelerating the development of the skeleton
and reproductive organs, which has been supposed to indicate that it
normally exerts a restraining or regulative influence on this develop-
ment, is at present purely fanciful.
Kidney. — The experiments of Bradford, which seemed to indicate
that the kidney, in addition to its function as an excretory organ, plays
an important, and indeed indispensable, part in protein metabolism,
possibly by forming something of the nature of an internal secretion,
Fig. 218.— Effect of Bone-Marrow on Blood-Pressure. Intravenous Injection of
Saline Extract Vagi Intact. The uppermost line is a signal trace showing the
time and length of injection. Below this is the record of the respirat ^ry move-
ments, and lowest the blood-pressure tracing. To be read from leU to right.
have not been confirmed. He stated that, when the half or two-thirds
of one kidney and the whole of the other have been removed from a
dog by successive operations, death ensues, although the quantity both
of water and urea excreted by the fragment of renal substance that
remains is far above the normal. In spite of the increased elimination
S^A thHatfsubs,tance ,was ^d to accumulate in the tissues.Towing
that the destruction of protein was increased— a conclusion which
seemed to derive support from the wasting of the animal. It has since
been shown that an increased output of nitrogen is not of constant
occurrence and only takes place under the same conditions aT^
starvation (p. 603). As a matter of fact, the animals waste and d£
672 INTERNAL SECRETION— ENDOCRINE GLANDS
within a few days or weeks largely because they refuse to eat. Polyuria
(increase of urine beyond the normal) does not necessarily occur. It
is well known that when only one kidney is extirpated the other hyper-
trophies, and no ill-effects ensue.
The statement that extracts of the kidney when injected into the
veins of an animal cause a rise of arterial blood-pressure, essentially
through direct action on the peripheral vaso-motor mechanism, is of
considerable interest, for it may possibly have some bearing on the rise
of pressure and consequent hypertrophy of the heart associated with
certain renal diseases. But there is not as yet sufficient evidence that
the hypothetical pressor substance, to which the name ' renin ' has
been given, in any sense represents an internal secretion of the kidney.
.^^ The pressor substance (so-called
^JpM||L ' urohypertensine ') which can be
Jfr ^\ extracted by ether from normal
^Jf \ human urine (Abelous) is probably
Ajyt^Mr \| only excreted by the kidney, and
KP^^ ^\ ^.^ perhaps arises from the putrefac-
\jM|N ^on °* proteins in the intestine.
If For it has been shown that in the
putrefaction of (horse-) meat bases
U«^^ rijfrf
, _ ••— — blood-pressure. The most active
Fig. 219. — Injection *of Extract of Bone- of these is a body known as
Marrow with the Vagi Cut. To be read ^-hydroxyphenylethylamine,
from left to right. formed from tyrosin (Barger and
Walpole). Whether the pressor
(vaso-constrictor) substance which appears to be liberated from the
platelets when blood is shed, and may therefore be presumed to be more
slowly liberated from such platelets as normally break down in the
circulating blood, has any relation to the pressor substance of urine
is unknown. It is also quite uncertain whether, as has been stated by
some observers, extracts of the kidney or blood from the renal vein
stave off for a time the onset of the uraemic symptoms that follow
removal of both kidneys or ameliorate them when they have already
appeared.
Spleen. — The spleen does not produce an internal secretion
necessary to life, for it can be removed both in animals and in
man, without the development of serious symptoms. Its blood-
forming and blood-destroying functions (p. 22) are taken on by
other structures (particularly the red bone-marrow).
The most definite changes following splenectomy are transient
anaemia, increased resistance to haemolytic agents, and an increase
in the content of cholesterol in the blood (Pearce). These effects
are more pronounced in the young. This is intelligible if the spleen
normally plays a considerable part in the destruction of worn-out
erythrocytes with liberation of haemoglobin, the source of the bile-
pigment. The formation of the bile-pigment is said to be inter-
fered with, and its amount reduced by more than 50 per cent.
(Pugliese).
The spleen can be auto-transplanted readily into the subcutaneous
tissues of animals. There is a great difference in the behaviour of
ADRENALS 673
such transplants according to the age of the animal (Marine and
Manley). In young rabbits, the transplants grow rapidly if the
spleen is removed at the time of transplantation, while in sexually
mature rabbits they do not grow and often undergo gradual absorp-
tion. Likewise, transplants which have grown rapidly in young
animals decrease in size after adult life is reached, indicating that
the function of the spleen is more necessary in young than in older
animals ; or that its function is more easily and completely assumed
by other tissues, probably the bone marrow, in adults. A further
and very suggestive fact, is that a subcutaneous spleen graft which
has ' taken,' but is not growing, in a young animal whose spleen has
not been removed, can be made to grow by removal of the spleen.
These results indicate that splenic insufficiency is a necessary con-
dition of growth of a splenic transplant, just as thyroid insufficiency
is a necessary condition of growth of a thyroid transplant. The
stimulus to growth in the one case, as in the other, must be assumed
to be a chemical stimulus transmitted through the blood, and not
dependent upon the nervous system.
The salivary glands may be extirpated without any sensible change
being produced in the normal metabolism. It has been stated how-
ever, that the secretion of the gastric juice is diminished. It has been
supposed that this may be due to the absence of a hormone (p. 404)
normally produced in the salivary glands. A temporary increase in
the gastric secretion is said to be caused when extracts of the glands
of normal dogs are injected into the veins or into the peritoneal cavity
of dogs deprived of their salivary glands (Hemmeter). But later
experiments contradict the theory of the existence of a hormone in the
salivary glands, which stimulates the secretion of gastric juice. The
average rate of secretion into a Pawlow gastric pouch (p. 403) was not
diminished in dogs after extirpation of the glands (Swanson.)
Extracts of nervous tissue (sciatic nerve, white matter of brain, and
spinal cord, but especially grey matter of brain) cause, on injection into
the veins, a decided fall of arterial blood-pressure, which soon passes
off, and can be renewed by a fresh injection. The fall of pressure is
due to direct action upon the bloodvessels of a depressor substance in
the extracts, and not to the action of vaso-motor nerves. It can be
obtained after section of the vagi.
Extracts of muscular tissue also cause a distinct though transient
fall of pressure, but not so great a fall as in the case of extracts of
nervous tissue. Saline decoctions of other tissues (testis, kidney,
spleen, pancreas, liver, mucous membrane of stomach and intestine,
lung, and mammary gland) all produce a fall of blood-pressure (Osborne
and Vincent). The same is true of bone marrow (Brown and Guthrie;
Figs. 218, 219). It must be repeated that there is no evidence that
these depressor substances are specific internal secretions in the same
sense as epinephrin.
43
CHAPTER XII
ANIMAL HEAT
FROM the earliest ages it must have been noticed that the bodies of
many animals, and particularly of men, are warmer than the air
and than most objects around them. The ' vulgar opinion ' of
Bacon's time, ' that fishes are the least warm internally, and birds
the most,' if it does not imply a very extensive knowledge of animal
temperature, at least shows that the fundamental distinction of
warm and cold-blooded animals, which is to-day more accurately
expressed as the distinction between animals of constant tempera-
ture (homoiothermal) and animals of variable temperature (poi kilo-
thermal), had been grasped, and was even popularly known. Since
that time the accumulation of accurate numerical results, and the
advance of physical and physiological doctrine, have given us
definite ideas as to the relation of animal heat to the metabolic
processes of the body. It is impossible to understand the present
position of the subject without an elementary knowledge of the
science of heat. For this the student is referred to a textbook of
physics. All that can be done here is to preface the physiological
portion of the subject by a few remarks on the physical methods and
instruments employed:
SECTION I. — THERMOMETRY AND CALORIMETRY.
Temperature. — Two bodies are at the same temperature if, when
placed in contact, no exchange of heat takes place between them.
They are at different temperatures if, on the whole, heat passes from
one to the other, and that body from which the heat passes is at the
higher temperature. It is known by experiment that if two bodies of
different temperature are placed in contact, heat will pass from one to
the other till they come to have the same temperature. If, then, we
have the means of finding out the temperature of any one body, we
can arrive at the temperature of any other by placing the two in con-
tact for a sufficiently long time, under the proviso that the quantity of
heat necessary to bring the temperature of the first body, which may be
called the ' measuring ' body, to equality with that of the second is so
small as not to make a sensible difference in the latter. This is the
principle on which thermo metric measurements depend. A mercurial
thermometer consists of a quantity of mercury ordinarily contained in
a thin glass bulb, the cavity of which is continued into a tube of very
674
THERMOMETRY AND CALORIMETRY 675
fine bore in the stem. Like most other substances, mercury expands
when the temperature rises, and contracts when it sinks, and the amount
of expansion or contraction is shown by the rise or fall of the mercurial
column in the stem of the thermometer. The point at which the
meniscus stands when the bulb is immersed in melting ice or ice-cold
water is, on the centigrade scale, taken as zero ; the point at which it
stands when the thermometer is surrounded by the steam rising from
a vessel of boiling water is taken as 100 degrees. The intermediate
portion of the stem is divided into degrees and fractions of degrees.
When, now, we measure the temperature of any part of an animal with
such a thermometer, we place the bulb in contact with the part until
the mercury has ceased to rise or fall. We know then that the mercury
has ceased to expand or contract, and therefore that its temperature
is stationary, and presumably the same as that of the part. It is to
be noted that we have gamed no information whatever as to the amount
of heat in the body of the animal. We have only observed that the
mercury of the thermometer when its temperature is the same as that
of the given part expands to an extent marked by the division of the
scale at which the column is stationary. And we know that if the
mercury rises to the same point when the thermometer is applied to
another part, the temperature of the latter is the same as that of the
first part; if the mercury rises higher, the temperature is greater; if
not so high, it is less. The thermometer, then, only informs us whether
heat would flow from or into the part with which it is in contact if
the part were placed in thermal connection with any other body of
which the temperature is known. In other words, the temperature is
a measure of the heat ' tension,' so to speak; and difference of tempera-
ture between two bodies is analogous to difference of potential between
the poles of a voltaic cell (p. 724), or to difference of level between the
surface of a mill-pond and the race below the wheel.
The temperature of an animal is measured in one of the natural
cavities, as the rectum, vagina, mouth, or external ear, or in the axilla,
or at any part of the skin. For the cavities a mercury thermometer
is nearly always used ; the ordinary little maximum thermometer is most
convenient for clinical purposes. The temperature of the skin may be
measured by an ordinary mercury thermometer, the outer portion of
the bulb of which is covered by some badly conducting material. An
uncovered thermometer, heated nearly to the temperature expected,
will also give results sufficiently accurate for most purposes, especially
if the bulb is flat or in the form of a flat spiral, which can be easily
applied to the surface. A theoretically better method, but more
laborious in practice, is the use of a thermo-electric junction, or a resist-
ance thermometer formed of a grating cut out of thin lead-paper or tin-
foil (Fig. 220). This is especially useful for comparing the temperature
of two portions of skin . The temperature of the solid tissues and liquids
of the body may also be measured or compared by the insertion of mer-
curial or resistance thermometers or thermo-electric junctions (p. 764).
Calorimetry. — The quantity of heat given off by an animal is generally
measured by the rise of temperature which it produces in a known
mass of some standard substance. Sometimes, however, as in the ice-
calorimeter of Lavoisier and Laplace, and the ether calorimeter of
Rosenthal, a physical change of state — in the one case liquefaction of
ice, in the other evaporation of ether — is taken as token and measure
of heat received by the measuring substance, the number of units of
heat corresponding to liquefaction of unit mass of ice or evaporation of
unit mass of ether being known. The unit generally adopted in the
measurement of heat is the quantity required to raise the temperature
676
ANIMAL HEAT
of a kilogramme of water i° C., which is called a calorie,* or kilocalorie
or large calorie. The thousandth part of this, the quantity needed to
raise the temperature of a gramme of water by i°, is termed a small
calorie or millicalorie or gramme-calorie.
In the calorimeters which have been chiefly used in physiology either
water or air has been taken as the measuring substance. The simplest
form of water calorimeter is a box with double walls, the space between
which is filled with a weighed quantity of water. The animal is placed
inside the vessel, and the temperature of the water noted at the begin-
ning and end of the experiment. Suppose that the quantity of water
is 10 kilos, and that the temperature rises i° in thirty minutes, then the
amount of heat lost by the animal is
10 calories in the half -hour, or 480
calories in the twenty -four hours; and
if the rectal temperature is unchanged,
this will also be the amount of heat
produced.
Here we assume (i) that all the heat
lost by the animal has gone to heat the
water and none to heat the metal of the
calorimeter; (2) that none has been
radiated away from the outer surface of
the latter. The first assumption will
seldom introduce any sensible error in a
prolonged physiological experiment ; but
it is very easy to determine by a separate
observation the water-equivalent of the
calorimeter — that is, the quantity of
water whose temperature will be raised i °
by a quantity of heat which j ust suffices
to raise the temperature of the metal by
i° (p. 721). Then the water-equivalent
is added to the quantity of water actu-
ally present, and the sum is multiplied by
the rise of temperature. If the tempera-
ture of the room is constant, as will be
approximately the case in a cellar, any
error due to interchange of heat between
Fig. 320. — Resistance Thermom-
eter for measuring Temperature
of Skin. G, grating of lead-
paper, attached to a cover-slip,
and mounted on a holder; W,
W, wires to the Wheatstone's
bridge. An increase of tem-
perature causes an increase in
the resistance of the lead. The
balance of the bridge is thus dis-
turbed. By experimental grad-
uation the temperature value
of the deflection, or of the change
of resistance that balances it, is
known (p. 725).
the calorimeter and its surroundings may be eliminated by making the
initial temperature of the water as much less than that of the air as the
final temperature exceeds it. Then if the loss of heat by the animal is
uniform, as much heat is gained during the first half of the experiment
by the calorimeter from the air as is lost by it to the air during the last
half. Or, without lowering the temperature of the water, the amount
of heat lost by the calorimeter during an experiment may be previously
determined by a special observation, and added to the quantity cal-
culated from the observed rise of temperature. Or, finally, two similar
calorimeters may be used, one containing the animal and the other a
hydrogen flame, or a coil of wire traversed by a voltaic current, which
is regulated so as to keep the temperature the same in the two calorim-
eters. From the quantity of hydrogen burnt, or electricity passed,
the heat-production of the animal can be calculated.
In Atwater's great respiration calorimeter (Fig. 221) both the heat
production and the respiratory exchange are measured. The heat pro-
duced by the person in the calorimeter is carried away from it by a
* The student should carefully note that when the term ' calorie ' is used
without qualification, a large calorie, i.e., 1,000 gramme-calories, is meant.
THERMOMETRY AND CALORIMETRY
677
stream of water flowing through the chamber in a series of tubes, the
temperature within the calorimeter being kept constant by regulating
the temperature and velocity of the entering stream of water. The
quantity of the escaping water and the increase in its temperature are
measured, and the heat-production can then be calculated. The
apparatus consists of a chamber in which a human being can live for
several days and nights. A stream of air is supplied, and the chemical
changes produced in. this are investigated in the manner already
described (p. 240).
Fig. 22 1. —Respiration Calorimeter (Atwater). Interior of chamber. A corner 2 ANIMAL HEAT
and the nitrogen excretion are increased. These phenomena mav
last for several days (Ott, Richet, Aronsohn, and Sachs), and are
due to stimulation of the portions of the brain in the immediate
neighbour hoed of the injury. Electrical stimulation of this region
has a similar effect. When the temperature has returned to
normal, a fresh puncture may again cause a rise.
As to the manner in which these centres are excited, there is
some evidence that, in addition to any influence exerted on them
by afferent nerves, they are capable of being directly affected by
the temperature conditions of the blood passing through them, as
well as by numerous drugs. Thus it is stated by Barbour and Wing
that direct application of cold to the region of the corpus striatum.
especially its caudate nucleus, in rabbits causes a rise in the rectal
temperature, associated with shivering and consequent increase of
heat-production in the contracting muscles, and with peripheral
vaso-constriction and consequent diminution in the heat-loss.
The application of warmth has the opposite effect : the peripheral
bloodvessels dilate, the animal becomes quiet, and the rectal tern
perature falls.*
Some observers hold that the chief seat of the increased metab
olism in the puncture fever is the skeletal muscles, others the liver.
The question turns largely upon the success of the puncture ex-
periment after the previous administration of curara on the one
hand, and of strychnine on the other. For curara cuts out the
motor innervation of the skeletal muscles, and strychnine convul-
sions exhaust the store of hepatic glycogen. Certain investigators
have found that after an adequate dose of curara no puncture fever
can be obtained, and they locate the increased metabolism asso-
ciated with the fever in the muscles. Others maintain that even
after curara the puncture is followed by fever, but is not followed
by fever if strychnine has first been given. They accordingly con-
clude that the rapid combustion of the glycogen (or the dextrose
derived from it) is the primary factor in the increased metabolism.'
It may be pointed out, however, that neither experiment is a crucial
test. For if strychnine reduces the liver glycogen, it also reduces
the glycogen of the muscles. And if in the puncture fever the liver
glycogen is transformed into dextrose more rapidly than usual, the
dextrose is probably in great part used up in the muscles more
rapidly than usual, eiss it would appear in the urine. The effect
of strychnine on the puncture fever, then, is no proof that the
muscles are not essentially concerned in it. On the other hand, the
alleged absence of the fever after curara is not sufficient to show
that the muscles are alone concerned. For curara causes a lowering
of the body-temperature, which, if it be not overcompensated, may
* Other observers, however, have failed to confirm these results (Cloetta
and Waser).
PEVER 703
mask the fever. The positive result of the puncture in curarized
animals, which some observers say they have obtained, would, if
animals, which some observers say they have obtained, would, if
confirmed, be important evidence that the primary effect is not on
the muscles, or, at least, not solely on them, but would not prove
that it is on the liver. That the liver is concerned, however, is more
directly indicated by the fact that during the puncture fever the
liver continues to be what it is under normal conditions, the warmest
organ in the body, warmer than the blood in the root of the aorta
by about i° C. The most probable conclusion is that the increased
production of heat in this form of experimental fever is due to an
increased metabolism of carbo-hydrate (glycogen) both in the liver
and in the muscles.
Temperature Regulation in Hibernating Animals. — The behaviour
of hibernating mammals, such as the marmot, dormouse, hedgehog,
and bat, is of interest in connection with the temperature regulation.
In the active waking state these animals are homoiothermal, but in
profound winter sleep they are poikilothermal, the body-tempera-
ture rising and falling with that of the air. The rectal temperature
may be as low as 2° C. There is an intermediate state in which the
animal is partially awake, though inactive, and its temperature is
much below the normal, but considerably above that of its environ-
ment. In this condition it has an imperfect thermotaxis, something
like that of an ordinary mammal (including the human infant) in
the period of immaturity, immediately after birth. When the
hibernating mammal awakes the rise of temperature is enormous
and abrupt. The temperature of a dormouse rose in an hour from
13' 5° C. to 357° C., and that of a bat in fifteen minutes from 17° C.
to 34° C. (Pembrey).
Fevers. — Fever is a pathological process generally caused by the
poisonous products of bacteria, and characterized by a rise of
temperature above the limit of the daily variation (p. 712). It is
further associated with an increase in the rate of the heart and the
respiratory movements, and a diminution in the alkalies and carbon
dioxide of the blood. The total excretion of nitrogen is increased,
at least in proportion to the amount of protein ingested, indicating
an increase in the consumption of tissue-protein. The distribution
of the nitrogen among the urinary constituents is altered. The
ammonia (in the form of ammonium salts of organic acids), the
uric acid, and to a smaller extent the creatinin (Leathes), are in-
creased, while the urea is relatively decreased, even when its abso-
lute amount is greater than normal. Creatin, which is not normally
present in urine, unless the food contains it, may also appear in
fever (Shaffer). It has been suggested that the proximate cause of
fever is the action of bacterial poisons or of other substances on the
' heat centres,' and that antipyretics, or drugs which reduce the
temperature in fever, do so by restoring the centres to their normal
704 ANIMAL HEAT
state, by preventing the development of the poisons, aiding their
elimination, or antagonizing their action. In favour of this view,
it has been stated that when the basal ganglia are cut off, by section
of the pons, from their lower nervous connections, fever is no longer
produced by injection of cultures of bacteria which readily cause it
in an intact animal, while antipyrin has no influence upon
the temperature (Sawadowski). And while it is almost certain
that some pyrogenic or fever-producing agents — cocaine, e.g. — act
indirectly, through the brain or cord, it is quite possible that others
affect directly the activity of the tissues in general, just as some
antipyretics or fever-reducing agents, such as quinine, act imme-
diately upon the heat-forming tissues, so as to diminish their
metabolism, while others, like antipyrin, affect them through the
nervous system. Quinine has no influence upon ' puncture ' fever
in rabbits. A still more important action of antipyrin, and the
group of antipyretics to which it belongs, is the increase in the heat-
loss which they bring about by the dilatation of the bloodvessels
of the skin. This effect is also produced through the nervous system.
Fever is a condition so interesting from a physiological point of
view, and of such importance in practical medicine, that it will be
well to consider a little more closely the possible ways in which a
rise of temperature may occur. It must not be forgotten that the
febrile increase of temperature is always accompanied by other
departures from the normal, and that all the fundamental febrile
changes may even, in certain cases, be present without elevation,
and even with diminution of temperature. But here we have only
to do with the disturbance of the normal equilibrium between the
loss and the production of heat; and it is evident that any of the
five conditions illustrated in the diagram (Fig. 226) may give rise
to an increase of temperature. It is not necessary to discuss
whether cases of fever can actually be found to illustrate every one
of these possibilities. It is probable that not infrequently dimin-
ished loss and increased production may be both involved; and it
ought to be remembered that the healthy standard with which the
heat-production of a fever patient should be compared is not that
of a man doing hard work on a full diet, but that of a healthy person
in bed, and on the meagre fare of the sick-room. When this is kept
in view, the comparatively low heat-production and respiratory
exchange which have sometimes been found in fever cease to excite
surprise. But in any case, no mere change in the absolute quantities
of heat formed and lost is sufficient to explain the febrile rise of
temperature; there must be a change in the relative proportion.
That an increase in heat-production is not of itself enough to produce
fever is proved by the fact that severe muscular work, which in-
FEVER
7°5
creases the metabolism more than high fever, only causes in a
healthy man a rise of about i° C. in the rectal temperature. When
the work is over, the temperature comes rapidly back to normal.
The essence of the change in fever is a derangement of the mechanism
by which in the healthy body excess or defect of average metab-
olism, or of average heat-
loss, is at once compensated
and the equilibrium of tem-
perature maintained.
This derangement only lasts
as long as the temperature
is rising. -When it becomes
stationary at its maximum
we have again adjustment,
again equality of production
and escape of heat; but the
adjustment is now pitched
for a higher scale of tempera-
ture. A rough analogy, so
far as one part of the process
is concerned, may be found
in the behaviour of the
ordinary gas-regulator of a
water-bath. It can be ' set '
for any temperature. That
temperature, once reached,
remains constant within nar-
row limits of oscillation; but
the regulator can be equally
well adjusted for a higher or
a lower temperature. It is,
however, important to note that the equilibrium is more unstable
in fever than in health, so that changes of external temperature more
easily depress or increase the temperature of a fever patient than of
a healthy man.
Rosenthal has concluded from calorimetric observations that, in
the first stage of fever, while the temperature is rising, there is
always increased retention of heat. Maragliano actually found
evidence, by means of the plethysmograph, that the cutaneous
vessels are at this stage constricted, and that the constriction may
even precede the rise of temperature. The blood- flow in the feet
in cases of typhoid fever investigated by the calorimetric method
(p. 122) was not found to exceed the normal flow, and was usually
decidedly below the normal. Hyperexcitability of the vaso-con-
strictor mechanism of the peripheral parts, especially of the skin,
45
Fig. 226. — Diagram to show tha Possible
Relations between Heat- Production and
Heat -Loss in Fever.
706 ANIMAL HEAT
was present. All these observations lend support to the famous
* retention ' theory of Traube. It has been suggested that the
significance of the increased action of the cutaneous vaso-constrictor
mechanism in typhoid fever is that the peripheral vaso-constriction
is a compensatory arrangement which secures for the organs mainly
suffering from the infective process an increased flow of blood to
combat the infection. On this hypothesis the rise of temperature
in so far as it depends upon diminished loss of heat is a secondary
phenomenon inevitably following the redistribution of the blood,
and unavoidable except by a corresponding diminution in the total
metabolism. In the great majority of cases the production of heat
is also increased, on the average by 20 to 30 per cent, of the normal
production of a resting man. The increase may be much greater
during the chill which ushers in so many infections on account of
the muscular contractions in shivering. During the period of rising
temperature the production of heat is not necessarily increased.
At the height of the fever there is often, though apparently not
always, an increase in the heat-production. After the crisis, while
the fever is subsiding, the rate at which heat is lost rises sharply.
As to the explanation of the increase of metabolism in fever,
and especially of the increased metabolism of tissue-protein,
various views have been held. Some have gone so far as to say
that the increase is merely the consequence, not the cause, of
the rise of temperature. But the rebutting evidence which has
been brought against this view is strong and, indeed, overwhelming.
It is perfectly true that, when the temperature of the body is
artificially raised by preventing the free loss of heat for a sufficient
time (so-called physiological fever), the destruction of protein is
augmented. A fasting dog whose temperature was increased to
40° or 41° C. for twelve hours eliminated 37 per cent, more nitrogen
than when the body-temperature was normal. But this increase
in the protein metabolism could be entirely prevented by giving
the animal a sufficient amount of carbo-hydrate. Similar results
have been obtained in man. The carbon dioxide excretion and
oxygen absorption are, of course, also markedly increased. But the
increase in the nitrogen excretion is often much greater in fever than
any increase which can be brought about by artificially raising the
temperature of a healthy individual by means of hot baths. A
typhoid patient was found to lose 10-8 grammes of nitrogen a day
(corresponding to 318 grammes of muscle) during eight days of
fever (F. Miiller). A portion of the loss of nitrogen on the routine
fever regimen may be due to the fact that the ordinary typhoid
patient is really on a semi-starvation diet, the heat-equivalent cf
which is not much more than half his heat-production. Yet it
has not been found possible to completely prevent the loss of
FEVER 707
nitrogen by putting the fever patient on a diet rich in protein, or
on a diet containing a moderate amount of protein with a large
quantity of fat and carbo-hydrate, even when the total heat- value
of the diet is much in excess of the 32 or 33 calories per kilo of body-
weight which corresponds to the heat-production of a resting man.
Another suggestive fact is that the excessive excretion of nitrogen
does not run parallel with the rise of temperature in fever, but is
often most marked after the crisis. During the stage of defer-
vescence an enormous amount of urea is sometimes given off. In a
case of typhus, in the mixed urine of the third and fourth days after
the crisis, no less than 160 grammes of urea was found (Naunyn), or
nearly three times the normal amount for a man on full diet. Again,
when fever is caused by the injection of bacteria or their products,
the increase in the carbon dioxide eliminated and oxygen consumed
occurs even when the temperature is prevented from rising by cold
baths. It seems perfectly clear, then, that the increase of metab-
olism is, in many cases at least, a primary phenomenon of fever.
Its course and incidence, falling as it does so largely upon the
proteins, the steady loss of tissue nitrogen, and the inability of the
tissues to recoup their losses from the protein of the food or to
shield their own protein by burning more carbo-hydrate or fat, all
suggest that the cells are poisoned by toxic products of the infective
process. The poisoned bioplasm falls an easy prey to the hydro-
lysing and oxidizing agents always present in the tissues. It breaks
down more rapidly and builds itself up more slowly than normal
bioplasm. This increased, and to some extent perverted, metab-
olism, far from being occasioned by the febrile temperature, is quite
probably the cause of the thermo-regulative upset which we call fever.
For Mandel has shown — (i) that one of the purin bases (xanthin)
causes fever in monkeys; (2) that the purin bases in the urine are
increased both in infective fevers and the so-called aseptic or surgical
fever — that is, in cases where the temperature rises after such injuries
as extensive crushing of tissues without infection. There is a con-
stant relation between the height of the fever and the quantity of
purin bases excreted. The source of the purin bases in aseptic fever
is presumably the autolysis of the injured tissue, from which they
pass into the blood without being oxidized to uric acid. The xanthin
fever can be prevented by salicylates, though not by antipyrin.
It has been very generally admitted that the chief seat of excessive
metabolism in fever is the muscles; but U. Mosso has stated that
cocaine fever — the marked rise of temperature produced by injec-
tion of cocaine — can be obtained in animals paralyzed by curara.
This, even if true, would not support the conclusion that a ' nervous
fever ' — that is to say, a fever due solely to increased metabolism
in the nervous system — exists; for in a curarized animal a large
7o8 ANIMAL HEAT
amount of ' active ' tissue (glands, heart, smooth muscle) still
remains in physiological connection with the brain and cord. But,
as a matter of fact, in an animal under a dose of curara sufficient
to completely paralyze the skeletal muscle cocaine causes no appre-
ciable rise of rectal temperature ; and this is strongly in favour of
the view that the fever produced in the non-curarized animal is
connected with excessive muscular metabolism.
Significance of the Increased Temperature in Fever. — It remains
to ask whether the rise of temperature is anything more than a
superficial and, so to speak, an accidental circumstance. The
question has already been raised in discussing the changes in the
circulation in fever (p. 706). The orthodox view for many ages
has undoubtedly been that the increase of temperature is in itself
a serious part of the pathological process, a symptom to be fought
with and, if possible, removed. And, indeed, it is not denied by
anyone that the excessive rise of temperature seen in some cases of
febrile disease (to 43° C., or even to 45°) is, apart from all other
changes, a most imminent danger to life, unless, as is sometimes the
case (in influenza, e.g., where a temperature of 44° has been observed),
the high temperature lasts only a short time. Experimental heat
paralysis, a condition in which all voluntary and reflex movements
are abolished, is produced in frogs by raising the internal tempera-
ture to about 34° C. On cooling, the animal recovers. A similar
condition can be induced in mammals, but, of course, at a higher
temperature. The central nervous system succumbs before the
peripheral structures. The superior cervical ganglion in the cat 01
rabbit loses the power of transmitting nerve impulses at 50° C.
But some evidence has been brought forward, mostly from the field
of bacteriology, to support the idea that in infective processes the
rise of temperature is of the nature of a protective mechanism, that
the fever is, indeed, a consuming fire, but a fire -that wastes the body,
to destroy the bacteria. The streptococcus of erysipelas, for ex-
ample, does not develop at 39° to 40° C., and is killed at 39*5° to
41° C., and erysipelas infections in rabbits are less virulent if the
body -temperature be artificially raised. Anthrax bacilli, kept at
42° to 43° C. for some time, are attenuated, and when injected into
animals confer immunity to the disease. Heated for several days
to 41° to 42° C., pneumococci render rabbits immune to pneumonia,
and in rabbits in which ' puncture ' fever has been induced pneumo-
coccus infections run a milder course. These bacteriological results
are supported to a certain extent by clinical experience. For it has
been observed that a cholera patient with distinct fever has a
better chance of recovery than a case which shows no fever. But
too much weight ought not to be given to isolated facts of this sort,
and adverse evidence can be produced both from the laboratory
TEMPERATURE TOPOGRAPHY 709
and the hospital. For although hens are immune to anthrax under
ordinary conditions, but can be infected by inoculation when
artificially cooled, frogs, equally immune at the temperature of the
air, become susceptible when artificially heated. And it is impos-
sible to deny that the use of cold baths in typhoid fever is sometimes
of remarkable benefit. This benefit, however, while very unlikely
to be connected with any directly unfavourable action of the reduced
body-temperature on the growth of the bacilli, may perhaps be due,
in some part at least, to an increase in the cutaneous vaso-con-
striction which helps to send through the infected intestine a more
copious stream of blood.
SECTION IV. — DISTRIBUTION OF HEAT — -TEMPERATURE
TOPOGRAPHY.
The great foci of heat-formation — the muscles and glands — would,
if heat were not constantly leaving them, in a short time become
much warmer than the rest of the body ; while structures like the
bones, skin, and adipose tissue, in which chemical change and heat-
production are slow, would soon cool down to a temperature not
much exceeding that of the air. The circulation of the blood
insures that heat produced in any organ shall be carried away and
speedily distributed over the whole body; while direct conduction
also plays a considerable part in maintaining an approximately
uniform temperature. The uniformity, however, is only approxi-
mate. The temperature of the liver is several degrees higher than
that of the skin, and the temperature of the brain several degrees
higher than that of the cornea. The blood of the superficial veins
is colder than that of the corresponding arteries.
The crural vein, for example, carries colder blood than the crural
artery, and the external jugular than the carotid. The heat produced
in the deeper parts of the regions which they drain is more than counter-
balanced by the heat lost in the more superficial parts. When loss of
heat from the surface is sufficiently diminished by an artificial covering,
or prevented by the protected situation of any organ with an active
metabolism, the venous blood leaving it is warmer than the arterial
blood coming to it. The temperature of the blood passing from the
levator labii superioris muscle of the horse during mastication may be
sensibly higher than that of the blood which feeds it ; the blood in the
vena profunda femoris, and in the crural vein of a dog with the leg
wrapped in cotton-wool, is warmer byo-i°to 0-3° than of the crural
artery. The difference is due to the heat produced in the muscles, and it
ought to be of this order of magnitude. The quantity of blood in a
y-kilo dog is about £ kilo ; J of this, or ^ kilo, is in the skeletal muscles,
and the average circulation-time through them may be taken as ten
seconds. Six times in the minute, or 360 times in the hour, ^ kilo of
blood passes through the muscles, and is heated on the average by 0-2°.
"^60 "2
This represents a heat-production of about ^- x — , or 9 calories per
hour. Now, the total heat-production of a y-kilo dog is about
7io
ANIMAL HEAT
19 calories per hour, of which somewhat less than one-half is formed
in the skeletal muscles.
The blood of the inferior vena cava at the level of the kidneys may
be 0-1° colder than that of the abdominal aorta, but is warmer than
the blood of the superior cava. The right heart, therefore, receives
two streams of blood at different temperatures, which mingle in its
cavities. A controversy was long carried on as to the relative tem-
perature of the blood of the two sides of the heart; but the researches
of Heidenhain and Korner have shown that a thermometer passed into
the right ventricle through the jugular vein stands, as a rule, slightly
higher than a thermometer introduced through the carotid into the
left ventricle. The method gives not so much the temperature of the
blood in the two cavities as that of their walls. The thin-walled right
ventricle is heated by conduction from the warm liver, from which it is
only separated by the diaphragm, while the left ventricle loses heat
to the cooler lungs. The difference of temperature is not caused by
cooling of the blood in its passage through the pulmonary capillaries,
for even when respiration is suspended, a difference of temperature
between the two sides of the heart is found. Under ordinary circum-
stances, the inspired air is already heated almost to body-temperature
before it reaches the alveoli. But, while this is the case, a fall of less
than j\j° in the temperature of the blood passing through the lungs
would account for all the heat lost by the expired air. If half of the
loss took place in the upper air-passages, less than ^5° would be suffi-
cient. A slight difference of temperature in the blood of the two ven-
tricles might be caused, even in the absence of respiration, by the heat
developed in the cardiac 'muscle itself during contraction, a large pro-
portion of which must be conveyed by the coronary veins into the right
heart.
The surface temperature varies between rather wide limits with the
temperature of the environment. The temperature of cavities like
the rectum, vagina, and mouth, and of secretions like the urine, approxi-
mates to that of the blood in the great vessels or the heart, and under-
goes only slight changes. An increase in the velocity of the blood causes
the internal and surface temperatures to come nearer to each other,
the former falling and the latter rising. When the loss of heat from
a portion of the surface is prevented, the temperature of this portion
approaches the internal temperature. For this reason a thermometer
placed in the axilla approximately measures the internal temperature,
and not that of the skin; and a thermometer in the groin of a rabbit,
and completely covered by the flexed thigh, may stand as high as, or,
it is said, even higher than, a thermometer in the rectum (Hale White).
The temperature in the mouth is not a very reliable index of the deep
temperature of the body, especially in cold weather or after exercise,
as it is apt to be influenced by the inspired air. The mouth must, of
course, be kept closed during the measurement. On the average its
temperature is about the same as that of the axilla, and 0-4° C. below
that of the rectum. The rectal temperature is 0-2° or 0-3° above that
of the urine. In point of accuracy rectal observations are the best, and
next to them determinations of the temperature of the stream of urine.
The latter method, although subject to obvious limitations, is rapid and
free from the danger of conveying infection to the person (Pembrey).
The surface temperature is a rough index of the rate of heat-loss;
the internal temperature, of the rate of heat-production. A normal
skin temperature and a rising rectal temperature would probably in-
dicate increased production of heat; an increased rectal temperature,
TEMPERATURE TOPOGRAPHY 711
in conjunction with a diminished surface temperature, as in the cold
stage of ague, might be due either to diminished heat-loss while the
heat-production, remained normal, or to diminished heat-loss plus
increased heat-production.
The following tables illustrate the differences of temperature found
in the body. It should be remembered that the numbers are not
strictly comparable with each other; the temperature of the mammals
in which direct observations have been made on the blood is not
exactly the same as that of man, the temperature of the dog, for
example, being a little (about i° C.) higher. Then in the same animal
there is no very constant ratio between the temperature of the blood
in two vessels or of the skin at two points. Even in the same vessel
the temperature may vary with many circumstances, such as the
velocity of the stream, and the state of activity of the organ from which
it comes. Apart from physiological variations, experimental fallacies
sometimes cause a want of constancy, especially in measurements of
blood temperature. The insertion of a mercurial thermometer into a
vessel is very likely to obstruct the passage of the blood; and if the
blood lingers in a warm organ, it will be heated beyond the normal.
In man the blood-temperature in the arteries at the wrist has been
estimated indirectly by the calorimetric method of measuring the
blood-flow in the hand (p. 122), probably with greater accuracy than
would be attainable by the direct insertion of a thermometer, were
this permissible. The temperature of the calorimeter is determined at
which it neither imparts heat to the blood nor gains heat from the blood.
On the assumption that the heat-production of the resting hand is
negligible for this purpose,* the temperature so fixed will be that at
which the blood enters the hand — i.e., the temperature of the arterial
blood at the wrist.
Blood. (Dog.)
Right heart - - - - 38-8° C.
Left ,, - - 38-6
Aorta - - 38-7
Superior vena cava - - 36-8
Inferior ,, ... 38-1
Crural vein- - ... 37-2!
,, artery - 38-0
Profunda femoris vein - 38-2
Portal vein - 38-39 ) Varies with activity
Hepatic vein - - 38-4-39- 7 / of digestive organs.
Arterial blood at wrist in man - 0-5 below rectal temperature.
* Since, of course, some heat is produced in the hand even at rest, although
doubtless less per unit of weight than in the resting body as a whole, the
arterial blood temperature as thus determined must be somewhat too high.
No error is caused by this in the calculation of the blood-flow in the hand
(p. 122) ; for while the factor T — T' in the denominator is somewhat too great,
thtt corresponding quantity of heat produced in the hand is included in H in
the numerator.
f The following numbers were obtained (in an anaesthetized dog whose
rectal temperature had fallen 2° C.) for the temperature of the walls of the
crural artery and vein, as measured by an electrical resistance thermometer.
Leg of dog lightly wrapped in wool. ~\
Crural artery 34'95
,, vein ------ 34-76 1 Rectum, 36*2
Leg more carefully wrapped up. [Air, i6'3
Crural artery ----- 34-70
7" ANIMAL HEAT
Tissues.
Brain - - - - - - 40° C
Liver. - - 40-6-40*9
Subcutaneous tissue 2-1 lower than,
that of subjacent muscles (man).
Anterior chamber of eye - - 31-9) / uu--n
Vitreous humour - - 36-i}(rabblt)-
Cavities. (Man.)
Axilla - 36-3-37-5° C. (97'3-99-5° F-)-
Rectum - 36-37-8
Mouth - - 37-25
Vagina - - 37-5-38
Uterus - - 37-7-38-3
External auditory meal us - 37'3-37'8
Bladder (temperature of the
escaping urine) - - 36-0-37-5
Respiratory Passages. (Horse.)
Air fMiddle of nasal cavity - - 23-4° C.
temperature, j ,, trachea - - 32-4 in inspiration.
4-5° C. I ,t ». - 34'4 in expiration.
Natural Surfaces*
Cheek (boy, immediately after running) - 36-25°
f Anterior surface of forearm - 33'5-34'4
(Man) Posterior ,, ,, - 34-0
Room J Skin over biceps - 35-0
temperature ,'\ ,, ,, head of tibia - - 31-9
17-5° ,, immediately below xiphoid cartilage - 34-7
^ ,, over sternum - - 33^2
On hair (boy) - - 30-0
Under hair over sagittal suture (boy) - 33'7-34'O
Shaved skin of neck (rabbit) - 36-5
On hair ,, ,, - 31-5
,, between eyes ,, - - - 30-7
Artificial Surfaces.
(Surface of trousers over thigh - 23-7-28-7°
temperature, coat over arm
j_._o ,, waistcoat ----- 26-0
Normal Variations in the Temperature. — The internal tempera-
ture, as has been already said, is not strictly constant. It varies
with the time of day; with the taking of food; with age; to some
extent with violent changes in the external temperature, such as
those produced by hot or cold baths; and possibly with sex. On
the average the range of variation in the temperature of the rectum
or urine of a healthy man is from 36-0° C. (96-8° F.) to 37*8° C.
(100-0° F.).
In the monkey a very distinct and constant diurnal variation has
been observed, and the range is much wider than in man (as much
as 5*4° F.), the maximum falling between 6 and 8 p.m. and the
minimum between 2 and 4 a.m. (Simpson).
TEMPERATURE TOPOGRAPHY
713
The daily curve of temperature shows a minimum in the early
morning, between two and six o'clock (36-3° C.), and a maximum
in the evening, between five and eight o'clock (37*5° C.) ,(Fig. 227),
The daily range in health may be taken as a little over i° C., 01
about 2° F. In fever it is generally greater, but the maximum and
minimum fall at the same periods; and it is of scientific, and also
of practical, interest that the early morning, when the temperature
and pulse-rate are at their minimum, is often the time at which the
flagging powers of the sick give way. From two to six o'clock in
the morning the daily tide
of life may be said to reach
low-water mark. Even in
a fasting man the diurnal
temperature curve runs its
course, but the variations
are not so great. The ta-
king of food of itself causes
an increase of temperature,
although in a healthy man
this rarely amounts to more
than half a degree. The rise
of temperature is certainly
due in part to the increased
work of the alimentary
canal, but it is in the main
connected with the increase
of metabolic activity which the entrance of the products of digestion
into the blood brings about. The heat-production is especially
increased by proteins.
A dog weighing 15-3 kilos, the heat-production of which was 22-3 calo-
ries during an hour previous to feeding, was given 1,200 grammes of
meat at noon. The heat-production rose to 36 calories in the 2nd hour,
and 42 calories in the 3rd. It remained above 40 calories per hour
beyond the loth hour, and in the i4th hour it had only fallen to 37 calo-
ries, to reach 25 calories in the 2ist hour. On the whole, the increase
in heat-production ran parallel with, and was proportional to, the
increase in the excretion of nitrogen (Williams, Richie and Lusk).
The relatively unimportant share taken by the increased work of the
gastro-intestinal tract in the augmentation of the metabolism is illus-
trated by the fact that a high rate of heat-production was maintained till
the 1 4th hour, even although by this time three-quarters of the nitrogen
corresponding to the food protein had been eliminated in the urine, and
the work of digestion and absorption must have been largely completed.
The rise of temperature during digestion is gradual, the maximum
being reached during the fourth hour, or even later.
The cause of the daily variation of temperature has been much
discussed. There is no doubt that several factors are concerned,
among the most important being the variation in the amount of
contraction of the skeletal muscles and the influence of food. Mus-
Fig. zij. — Curve showing the Daily Variation
of Body-Temperature.
425 MS
cular exercise is capable of causing a considerable rise in the tem-
perature of the rectum and urine, to 38*5° C. (101-3° F.) or even
38*9° C. (102° F.) without producing any feeling of distress. Other
unknown influences seem also to be involved, as is shown by the
fact that in persons who work at night and sleep during the day
the curve of temperature, although greatly altered, is not reversed.
Recent observations on this subject are those of Benedict. By
means of a resistance thermometer in the rectum, readings were
taken usually every four minutes.
With such a thermometer no disturb-
ance of the person's sleep is necessary
to obtain a reading. He can sit with-
out discomfort in any position, walk
about the room (returning to the ob-
server's table for the observations),
and even ride a stationary bicycle.
Even years of night- work do not elim-
inate the tendency to a fall of tempera-
ture at night, a minimum in the early
morning, and a morning rise.
As to the relation of age and sex to
temperature, it is only necessary to
remark that the mean temperature
both of the young child and of the
old man is somewhat higher than
that of the vigorous adult; but a
point of more importance is the rela-
tive imperfection of the heat-regulation
in infancy and age, and the greater
effect of accidental circumstances on
the mean temperature. Thus, old people and young children are
specially liable to chills, and a fit of crying may be sufficient to
send up the temperature of a baby. In infants an hour or two old
the temperature may be as low as 34° C. (93*2° F.) or 33*0° C.
(91-4° F.) even when they are fully clothed in a room at 15° C.
(59° F.). It rises gradually during the first day or two, but shows
marked variations. On the fifth day after birth, e.g., the rectal
temperature ranged from 36*2° C. (97-16° F.) to 33-5° C. (92-3° F.)
in a child weighing 5^ pounds (Babak). The temperature of women
is generally a little higher than that of men, and is also somewhat
more variable. A fall of temperature, rarely amounting to more
than i° F., is associated with the menstrual period.
After death the body cools at first rapidly, then more slowly
(Fig. 2:8). But occasionally a post-mortem rise of temperature
may take place. In certain acute diseases (like tetanus) associated
with excessive muscular contraction this has been especially noticed;
in bodies wasted by prolonged illness it does not occur. Nearly an
28
Fig. 228. — Curve of Cooling after
Death : Guinea - Pig. Time
marked along horizontal, and
temperature along vertical axis.
At a ether and chloroform
given to kill animal; death, as
indicated by stoppage of the
heart, took place at b. The
dotted line shows the course
the curve would have taken if
death had occurred at the
moment the anaesthetics were
given. Air of room i7-6°.
PRACTICAL EXERCISES 715
hour after death, in a case of tetanus, the temperature was found
to be 45-3°, while before death it was 44-7° (Wunderlich). In dogs
a slight post-mortem rise may be demonstrated, especially when
the body is wrapped up; but when an animal has been long under
the influence of anaesthetics no indication whatever of the phenom-
enon may be obtained. The explanation of post-mortem rise of
temperature is to be found : (i) In the continued metabolism of the
tissues for some time after the heart has ceased to beat, for the cell
dies harder than the body. (2) In the diminished loss of heat, due
to the stoppage of the circulation. (3) To a small extent in physical
changes (rigor mortis, coagulation of blood) in which heat is set free.
PRACTICAL EXERCISES ON CHAPTERS X., XI., AND XII.
i. Glycogen* — (i) Preparation. — (a) Cut an oyster into two or three
pieces, throw it into boiling water, and boil for a minute or two. Rub
up in a mortar with clean sand, and again boil. Filter. Precipitate
any proteins which have not been coagulated, by adding alternately
a drop or two of hydrochloric acid and a few drops of potassio-mercuric
iodide so long as a precipitate is produced. Only a small quantity of
these reagents will be required, as the 'greater part of the proteins has
been already coagulated by boiling. Filter if any precipitate has formed.
The nitrate is opalescent . Precipitate the glyco gen from the nitrate (after
concentration on the water-bath if it exceeds a few c.c. in bulk) by the
addition of four or five times its volume of alcohol. Filter off the precipi-
tate, wash it on the filter with alcohol, and dissolve it in a little water.
To some of the solution add a drop or two of iodine ; a reddish-brown
(port wine) colour is produced, which disappears on heating, returns on
cooling, is removed by an alkali, restored by an acid. Add saliva to some
of the glycogen solution, and put in a bath at 40° C. In a few minutes
reducing sugar (maltose) will be found in it by Trommer's test (p. 10).
Note that dextrin (erythrodextrin) gives the same colour with iodine
as glycogen does. Dextrin is also precipitated by alcohol, but a
greater proportion must be added to cause complete precipitation.
Glycogen is completely precipitated by saturation with magnesium
sulphate or ammonium sulphate, so that the filtrate no longer gives
the reddish colour with iodine. A pure solution of erythrodextrin is
not precipitated. On the addition of a drop or two of a solution of
basic lead acetate to a solution of glycogen in distilled water, a pre-
cipitate forms immediately. When the same reagent is added to a
solution of dextrin in distilled water there is no immediate precipitate.
Maltose is formed when dextrin is digested with saliva.
(&) Cut another oyster into pieces, throw it into boiling water acidu-
lated with dilute acetic acid, and boil for a few minutes. Rub up in a
mortar with sand, boil again, and filter. Test a portion of the ni-
trate with iodine for glycogen. Precipitate the rest with alcohol,
filter, dissolve the precipitate in water, and test again for glycogen.
On boiling some of the opalescent solution for a few minutes after the
addition of a few drops of sulphuric acid the opalescence disappears, and
* For the quantitative estimation of glycogen in organs, Pfluger's method
is the best. The organ is minced and heated with strong (60 per cent.) potas-
sium hydroxide. The glycogen is precipitated with alcohol, and then, after
hydrolysis with hydrochloric acid, estimated as dextrose.
716 METABOLISM AND ANIMAL HEAT
when the solution has been neutralized with sodium hydroxide it gives
Trommer's test, owing to the hydrolysis of the glycogen into dextrose.
(2) Deeply etherize a dog or rabbit five hours after a meal rich in
carbo-hydrates — e.g., rice and potatoes in the case of the dog, carrots
in the case of the rabbit. Fasten it on a holder. Clip off the hair
over the abdomen in the middle line. Make a mesial incision through
the skin and abdominal wall from the ensiform cartilage to the pubis.
The liver will now be rapidly cut out (by the demonstrator) and divided
into two portions, one of which will be (distributed among the class
and) treated as in (a) or (b) ; the other will be kept for an hour at a
temperature of 40° C., and then subjected to process (a) or (b). Little,
if any, sugar and much glycogen will be found in the portion which
was boiled immediately after excision. Abundance of sugar will be
found in the portion kept at 40° C. ; it may or may not contain glycogen.
2. Catheterism. — In many physiological experiments it is necessary
to obtain urine from the bladder by means of a catheter. It is possible
to pass a fine rubber catheter into the bladder of a male dog. A
larger one is easily passed in a male rabbit, and a still larger in a bitch,
which is often used for experiments on metabolism. Even in the bitch
the opening of the urethra lies entirely concealed within the vagina,
much deeper than the cul-de-sac in the mucous membrane, into which
the beginner usually tries to force the catheter. For a first attempt
the animal should be etherized and fastened on a holder. The little
or index finger of the left hand is passed into the vagina till the sym-
physis pubis can be felt. A little below this is the opening of the
urethra. With the right hand the point of a catheter of suitable
calibre is directed along the finger, and after a little ' guess and trial '
it slips into the bladder, its entrance being announced by the escape of
urine. A glass tube drawn out to a sufficiently small calibre and bent
near the point is the easiest form of catheter to pass in a bitch. The
point must, of course, be rounded in the flame. The insertion of the
catheter is much facilitated by the use of a speculum.
When the bitch is to be used in a long series of experiments an
operation is sometimes performed first of all to render the urethral
orifice more accessible.
3. Glycosuria. — (i) (a) Weigh a dog (female by preference) or rabbit.
Fasten on a holder, and etherize. Insert a glass cannula into the
femoral or saphena vein of the dog, or into the jugular of the rabbit
(p. 214). Fill a burette with a 2 per cent, solution of dextrose in
physiological salt solution, connect it with the cannula by means of an
indiarubber tube, taking care that there are no air-bubbles in the tube,
and slowly inject as much of the solution as will amount to £ or f- grm.
of sugar per kilo of body- weight. Tie the vein, remove the cannula, and
in half an hour evacuate the bladder by passing a catheter, by pressure
on the abdomen, or, if both of these methods fail, by tapping the bladder
with a trocar pushed through the linea alba (supra pubic puncture).
In an hour again draw off the urine. Test both specimens for sugar.
In this experiment the opportunity may also be taken to demon-
strate that egg-albumin, when injected into the blood, is excreted by
the kidneys, a filtered solution containing the albumin of one egg and
sugar in the quantity mentioned being injected.
The catheter may be inserted before the injection is begun, and the
bladder evacuated. After the injection the urine that drops from the
catheter may be collected in test-tubes, first every two minutes, and
then, as soon as sugar is found, every ten minutes. Determine the
interval between injection and the appearance of the first trace of
sugar and albumin. If a sufficient amount of urine is obtained, the
PRACTICAL EXERCISES 7*7
quantity of sugar in successive specimens may be estimated and com-
pared. The rate of flow of the urine as measured by the number of
drops falling from the catheter may also be estimated from time to time
in order to determine whether diuresis is taking place.
If a rabbit is used for this experiment, the sugar solution may be
injected into the ear vein. The vein is caused to swell up by pressing
on it with the finger and thumb, and the hypodermic needle is then
inserted towards the heart.
(b) Instead of collecting the urine by a catheter in the bladder, the
abdomen of the dog may be opened, and a cannula tied into each ureter.
The two cannulse are then connected by short rubber tubes with a
glass Y-piece, on the stem of which a test-tube is tied for collecting the
urine. Replace the test-tube by a fresh one from time to time. The
urine already in the bladder is removed by pressure or by a trocar, and
tested for sugar, since the anaesthetic itself may cause a certain amount
of glycosuria. Test the samples of urine obtained from the ureters
for sugar, and in those in which it is present estimate its amount. Note
also any changes in the rate of secretion of urine, and any abnormal
constituents, as albumin.
(2) Phlorhizin Glycosuria. — Dissolve J grm. of phlorhizin in warm
water, and inject it subcutaneously into a rabbit. Obtain a sample of
the urine at the end of two hours, by pressure on the abdomen with
the thumb or by passing a catheter, and test for sugar. If none is
present, wait some time longer, and again test the urine.
This experiment can also be performed without risk on man. One
grm. of phlorhizin has been injected twice a day without disturbing the
individual. Much sugar is found in the urine, but it disappears the
day after the administration of phlorhizin is stopped. The phlorhizin
may also be given by the mouth, but more is required, and it is not
very easily absorbed, and often causes diarrhoea (v. Mering).
(3) Alimentary Glycosuria. — The urine having been tested for sugar
for two successive days, and none being found —
(a) A large quantity of dextrose is to be taken in the form which is
most agreeable to the student some hours after a meal. The urine of
the next twenty -four hours is to be collected and measured. A sample
of it is then to be tested for reducing sugar by Trommer's and the
phenyl-hydrazine test. If any sugar is found, the reducing power of a
definite quantity of the urine is to be determined by titration with
Fehling's solution (p. 526).
(b) Instead of dextrose use cane-sugar and proceed as in (a). But
estimate the reducing power of the urine (a) before and (/3) after boiling
with hydrochloric acid (p. 465).
(c) A large meal of rice and arrowroot, sweetened with as much dex-
trose as the observer can induce himself to swallow, is to be taken, and
the urine treated as in (a).
(d) A large number of sweet oranges may be eaten.*
4. Estimation of the Sugar in Blood — Method of Lewis and Benedict,
somewhat modified. — The blood must be used immediately after being
drawn. When only a single sample is required it can be obtained by
puncturing a vein with a large-sized hypodermic needle. If a number
of students have to be provided with blood an animal may be killed
by decapitation. Long anesthetization is to be avoided, as this causes
hyperglycaemia. To take blood from a' vein, place a few crystals of
potassium oxalate in the tip of a 2 c.c. pipette, and having punctured the
vein with a needle, draw up blood into the pipette to a little above the
* These experiments may be distributed among the class so that each
student does one.
718 METABOLISM AND ANIMAL HEAT
mark. Allow the blood to run back just to the mark, and immediately
discharge the contents of the pipette into a large test tube (about 50 c.c.
capacity) containing 8 c.c. of distilled water. Shake until haemolysis
is complete. Then add 15 c.c. of saturated aqueous solution of pure
picric acid ; shake thoroughly to precipitate the proteins of the blood,
and filter through a small filter paper. Into each of two long narrow
test tubes (capacity about 25 c.c.), which have been marked accurately
with a file at 10 c.c., measure 7 c.c. of the filtrate, add 2 c.c. of the
saturated solution of picric acid and i c.c. of a 10 per cent, solution of
anhydrous sodium carbonate. A duplicate determination wrill thus be
made. The test tubes are placed in an autoclave (according to Pearce's
modification of the method), and the pressure gradually brought up to
20 to 25 pounds to the square inch (2-5 kilogrammes to the square centi-
metre), and kept at this level for twenty-five minutes. Picramic acid is
formed by the reducing action of the sugar, and from the amount of
picramic acid estimated by a colorimeter the amount of sugar is de-
duced. Let the autoclave cool down till the pressure is zero, remove
the tubes and allow them to cool to room temperature. Sufficient
water is now added to each tube to bring the volume back to the 10 c.c.
mark, and after shaking the contents are filtered through cotton into
the (Duboscq) colorimeter bottles. The determination is made by
comparison with a solution containing a known amount of pure dex-
trose which has been carried through the same process, or with a
picramic acid standard solution.*
A solution of pure dextrose may be used as a standard instead of the
picramic acid, as follows : Into a test tube place 4 c.c. of a solution,
corresponding to 0-56 milligramme dextrose; add 5 c.c. of the saturated
picric acid solution, and i c.c. of 10 per cent, solution of anhydrous
sodium carbonate. Place in the autoclave and proceed as above
described, bringing the final volume again to 10 c.c., and filtering
through cotton into one of the colorimeter bottles.
Calculation :
Reading of standard mgm. dextrose in standard^ mgm. dextrose per
Reading of unknown c.c. blood used J~ c.c. blood.
The amount of blood taken for each of the duplicate determinations
is •£§ x 2 c.c. =0-56 c.c. The standard=o-56 milligramme dextrose in
10 "c.c., so that the second fraction on the left side of the equation
becomes unity, and the reading of the standard divided by the reading
of the unknown gives at once the number of milligrammes of dextrose
in i c.c. of blood.
5. Milk. — (i) Examine a drop of fresh cow's milk with the micro-
scope. Note the fat globules of various sizes.
(2) Determine the specific gravity of the milk with a hydrometer
(lactometer). Then centrifugalize some of the milk to separate the
cream, which rises to the top of the tubes. Remove the cream and
determine the specific gravity of the skimmed milk. It will be found
to have increased, since the fat is of lower specific gravity than the
rest of the milk. Normal cow's milk has a specific gravity of 1,028
to 1,034, skimmed milk 1.033 to 1,037.
* Picramic acid, 56 milligrammes, anhydrous sodium carbonate, 100
milligrammes, and distilled water to make up 1,000 c.c. Dissolve the sodium
carbonate in about 50 c.c. of water, add the picramic acid and dissolve it
with the aid of heat. When cooled to room temperature add enough water
to make 1,000 c.c. Picramic acid obtained on the market varies in the amount
of colour produced in the preparation of this solution. The standard should
therefore be compared with a solution of pure dextrose which has been standard-
ized by another method, and then treated by the Lewis and Benedict method.
PRACTICAL EXERCISES 719
(3 ) Test the reaction of the milk to litmus-paper . It is slightly alkaline.
(4) (a) Put 10 c.c. of milk in a test-tube, and nearly fill it up with
water. Add strong acetic acid drop by drop. A precipitate of casein-
ogen is thrown down which entangles the fat, and carries it down
mechanically along with it. Filter off the precipitate. Keep the
filtrate for (b). Wash the precipitate with water, scrape a portion of
it off the filter, and add to it some 2 per cent, sodium carbonate solution.
The caseinogen dissolves, while the fat remains in suspension. The
solution gives the colour reactions for proteins (p. 8).
(6) Test some of the filtrate (p. 10) for lactose. Add dilute sodium
carbonate solution to another portion till it is only slightly acid. Boil,
and lactalbumin is coagulated. Remove the lactalbumin by filtering,
and test this filtrate for earthy (i.e., calcium and magnesium) phos-
phates by adding a few drops of ammonia, which precipitates them as
a slight cloud.
(c) To 5 c.c. of milk add an equal volume of saturated ammonium
sulphate solution. The caseinogen is precipitated, entangling the fat.
Filter off. The filtrate may be used to test for lactalbumin by boiling.
The addition of water to the precipitate of caseinogen (and fat) on the
filter causes the caseinogen to dissolve, as it is soluble in weak salt
solutions. Caseinogen can also be precipitated by saturating milk
with sodium chloride or magnesium sulphate.
(5) To 5 c-c- °* milk a(ld. a couple of drops of 20 per cent, sodium or
potassium hydroxide, and then a few c.c. of ether. Shake up. The
ether dissolves the fat, and the opacity of the milk diminishes. Take
off the ether with a pipette, evaporate away most of it on a water-bath,
and place a drop or two of the remainder on a filter-paper. A greasy
stain is left, showing the presence of the fat of the milk, or butter.
(6) Clotting of Milk. — (a) To a few c.c. of milk in a test-tube add a
few drops of rennet. Place the tube in a bath at 40° C. In a short
time a clot or curd is formed, consisting of casein, which is derived from
the caseinogen. The fat is entangled in the clot. On standing some
time the clot contracts, and exudes the whey. Boil some of the whey
after slight acidulation with acetic acid; the lactalbumin and whey-
protein are coagulated. Test another portion of whey for proteins by
one of the general protein tests (p. 8) — e.g., the xanthoproteic.
(b) Repeat (a) but use rennet which has been previously boiled. The
milk is not curdled, because the ferment has been inactivated by boiling.
(c) To 10 c.c. of milk add 3 c.c. of i per cent, potassium oxalate.
Divide the oxalated milk into three portions — A, B, and C. To A add
a few drops of rennet, to B i c.c. of 2 per cent, calcium chloride solu-
tion and a little rennet, and to C i c.c. of 2 per cent, calcium chloride
solution alone. Put the tubes at 40° C. Clotting will occur in B, but
not in A or C.
6. Cheese. — (i) Rub up some finely-grated cheese in a mortar with
2 per cent, sodium carbonate solution. Filter. The filtrate contains
casein, which can be precipitated by adding dilute acetic acid by drops
to a portion of the filtrate. The precipitate is soluble in excess of the
acid. With another portion of the filtrate perform some of the general
protein tests (p. 8).
(2) Shake up some finely-grated cheese in a dry test-tube with ether.
Take off the ether with a pipette, and evaporate on a water-bath till
only a few drops remain. With a glass rod put a drop of the ether on
a piece of filter-paper. A greasy spot is left, showing that fat is present.
7. Flour. — (i) Mix some wheat-flour v/ith a little water into a stiff
dough. Let it stand for a few minutes at body-temperature to facilitate
the formation of gluten. Wrap a piece in cheese-cloth, forming a kind
720 METABOLISM AND ANIMAL HEAT
of bag, and knead it with the fingers in a capsule of water. The
starch grains come through the cheese-cloth. Pour the water into a
beaker. It is opaque, and on standing the starch grains sink to the
bottom, (a) Test for starch with the iodine test, and also examine
microscopically. The grains are round, with a central hilum, and are
smaller than those of potato starch (p. n). (b) Test for sugar by
Trommer's test (p. 10). None is present unless the flour has been made
from inferior grain in which some germination has taken place.
(2) Go on kneading the dough till no more starch comes through.
The sticky mass which remains in the bag is a protein called gluten,
which is formed from certain globulins and other proteins in the flour
on addition of water. Oatmeal, ground rice, and other grains poor in
gluten-forming globulins do not form dough when mixed with water.
Suspend some of the gluten in water in a test-tube, and apply to it the
general protein colour tests (p. 8).
8. Bread. — (i) Rub up a small piece of the crumb of a stale loaf in a
mortar with water. Strain through cheese-cloth. The fluid which
passes through contains starch grains, (a) Filter it, and test a portion
of the filtrate for dextrose by Trommer's test. A positive result
is obtained. Test another portion with iodine for erythrodextrin.
(b) Test a portion of the residue of the bread which has not passed
through the cheese-cloth for protein by the general protein tests — e.g.,
the xanthroproteic or Millon's tests.
(2) Repeat (i) using the crust of the bread. Both dextrose and
erythrodextrin are present in the cold-water extract, but the dextrose
is less plentiful than in the crumb, having been converted into caramel
in the baking. The sugar and dextrin are formed from the starch of the
flour by the ferments of the yeast employed to make the bread rise.
9. Variations in the Total Nitrogen (p. 521) and in the Quantity of
Urea excreted, with Variations in the Amount of Proteins in the Food. —
The student should put himself, or somebody else if he can, for two days
on a diet poor in proteins, then (after an interval of forty-eight hours
on his ordinary food) for two days on a diet rich in proteins. A suitable
table of diets will be supplied. The urine should be collected on ths
six days of the period of experiment, on the day before it begins, and
on the day after it ends. Small samples of the mixed urine of the
twenty-four hours for each of these eight days should be brought to the
laboratory, and the quantity of urea determined by the hypobromite
method. The volume of the urine passed in each interval of twenty-
four hours being known, the total excretion of urea for the twenty-four
hours can be calculated, and a curve plotted to show how it varies
during the period of experiment.* If sufficient time is available, the
experiment will be made still more instructive by determining the
total nitrogen in each sample in addition to the urea. A curve showing
the variation in the total nitrogen can then be plotted on the same paper
as the urea curve, and a table calculated giving the percentage of the
total nitrogen contained in the urea for each day of the experiment.
10. Action of Epinephrin (Adrenalin). — Several experiments to illus-
trate this are given in the Practical Exercises following other chapters,
but may equally well be performed here. (See Experiment 8, p. 66;
Experiment 3, p. .453-.)
* In 17 healthy students the average amount of urea excreted in twenty
four hours on the ordinary diet was 29-51 grammes (minimum 19-35 grammes
maximum 46-01 grammes) ; on a diet poor in protein, average 20-75 grammes
(minimum 9-52 grammes, maximum 32-86 grammes) ; on a diet rich in protein,
average 38*83 grammes (minimum 23-26 grammes, maximum 67-82 grammes).
PRACTICAL EXERCISES 721
ii.* Measurement of the Quantity of Heat given off in Respiration. —
This may be done approximately as follows: Put in the inner copper
vessel, A, of the calorimeter shown in Fig. 224 (p. 682) a measured
quantity of water sufficient to completely cover the series of brass discs.
Place A in the wide outer cylinder, the bottom of which it is prevented
from touching by pieces of cork. The outer cylinder hinders loss of
heat to the air. Suspend a thermometer in the water through one of the
holes in the lid. In the other hole place a glass rod to serve as a stirrer,
Read off the temperature of the water. Put the glass tube connected
with the apparatus in the mouth, and breathe out through it as regu-
larly and normally as possible, closing the opening of the tube with
the tongue after each expiration and breathing in through the nose.
Continue this for five or ten minutes, taking care to stir the water fre-
quently. Then read off the temperature again. If W be the quantity
of water in c.c., and t the observed rise of temperature in degrees Centi-
grade, Wt equals the quantity of heat, expressed in small calories
(p. 675), given off by the respiratory tract in the time of the experiment,
on the assumptions (i) that all the heat has been absorbed by the water,
(2) that none of it has been lost by radiation and conduction from the
calorimeter to the surrounding air. Calculate the loss in twenty -four
hours on this basis ; then repeat the experiment, breathing as rapidly
and deeply as possible, so as to increase the amount of ventilation.
The quantity of heat given off will be found to be increased, f
In an experiment of short duration (2) is approximately fulfilled.
As to (i), it must be noted that in the first place the metal of the
calorimeter is heated as well as the water, and the water-equivalent
of the apparatus must be added to the weight of the water (p. 676).
The water-equivalent is determined by putting a definite weight of
water at air temperature T into the calorimeter, and then allowing a
quantity of hot water at known temperature T' to run into it, stirring
well, and noting the temperature of the water when it has ceased to
rise. Call this temperature T". Enough hot water should be added
to raise the temperature of the calorimeter about 2° C. The quantity
run in is obtained by weighing the calorimeter before and after the
hot water has been added. Suppose it is m. Let the mass of the cold
water in the calorimeter at first be M, and let M'=the mass of water
which would be raised i° C. in temperature by a quantity of heat suffi-
cient to increase the temperature of all the metal, etc., of the calorimeter
by i° — in other words, the water-equivalent of the calorimeter.
The rnass m of hot water has lost heat to the amount of m (T' — T"),
and this has gone to raise the temperature of a rnass of water M,
and metal equivalent to a mass of water M', by (T" — T) degrees.
.-. m (T'— T") = M(T"— T) + M'(T"— T). Everything in this equation
except M' is known, and .•'. M', the water-equivalent of the calorimeter,
can be deduced, and must be added in all exact experiments to the mass
of water contained in it.
Secondly, all the excess of heat in the expired over that in the inspired
air is not given off to the calorimeter, for the air passes out of it at a
slightly higher temperature than that of the atmosphere. At the
beginning of the experiment this excess of temperature is zero. If
at the end it is i° C., the mean excess 13 0-5° C. Now, when respiration
* This experiment is given as an example of a simple calorimetric measure-
ment, which can be easily performed with sufficient accuracy by students,
and involves the essential principles of such determinations.
f The average heat-loss by the lungs for 51 men (calculated for the 24 hours)
was 312,000 small calories for normal, 919,000 for the fastest, and 195,000 for
the slowest breathing.
722
METABOLISM AND ANIMAL HEAT
is carried on in a room at a temperature of 10° C., the expired air has
its temperature increased by nearly 30° C. About jfa of the heat
given off by the respiratory tract in raising the temperature of the air
of respiration would accordingly be lost in such an experiment. But
since the portion of the heat lost by the lungs which goes to heat the
expired air is only £ of the whole heat lost in respiration (p. 682), the
error would only amount to 5^ of the whole, and this is negligible.
Thirdly, the air leaves the calorimeter saturated with watery vapour
at, say.. 10-5°, while the inspired air is not saturated for 10° C. Now,
the quantity of heat rendered latent in the evaporation of water suffi-
cient to saturate a given quantity of air at 40° C. (the expired air is
saturated for body-temperature) is six times that required to saturate
the same quantity of air at 10°. If, then, the inspired air is half
saturated, the error under this head is -^ , or 8£ per cent. If the inspired
air is three-quarters saturated, the error is ^V or about 4 per cent. If the
air is fully saturated before inspiration, as is the case when it is drawn
in through a water-valve (Fig. 229) by a tube fixed in one nostril, the
only error is that due to the slight excess of temperature of the air
leaving the calorimeter over that of the inspired air. The latent heat
of the aqueous vapour in saturated air at 10-5° C. is about more
than the latent heat of the aqueous vapour in the same
mass of saturated air at 10° C., or about T^0 of the
latent heat in saturated air at 40°. The error in this
case would therefore be under i percent. The tubes
must be wide and the bottle large.
12. In the observations on the blood-flow in the
hands (Experiment 31, p. 219) data on the quantity
of heat given off by the hands when immersed in water
at a given temperature have already been obtained.
Additional data should be got by putting the hand
into the calorimeter without previous immersion in
the bath, and comparing the heat given off during
the period when the hand is acquiring the temperature
of the calorimeter with that (riven off when the steady
state has been reached. Different calorimeter tmi-
peratuies should be employed. It will be found that
as the calorimeter temperature is diminished the
quantity of heat given off may be increased although
the blood-flow is diminished, each gramme of blood passing through
the hand giving off more heat the lower the calorimeter temperature.
The quantity of heat lost by the hand, at a given temperature
of the calorimeter, per square centimetre of skin surface can be cal-
culated. If no special instrument for measuring the area of irregular
surfaces is available, the surface of the hand can be arrived at ap-
proximately by covering it with strips of gummed paper of known
breadth, and noting the length used to cover the whole hand up to the
lower level of the styloid process of the ulna. Or an old thin glove
which fits the hand can be cut off at this level and weighed. As large
a piece as possible of regular shape is then cut from the glove, weighed,
and its area deduced by measuring it with a rule. The area of the
whole glove, on the assumption that it is of uniform thickness, is thus
known. Or, without cutting the glove, it may be laid flat on a piece
of paper, an outline of it traced, and the paper cut out. The weight
of the paper cut out is compared with that of a piece of paper of known
area, and its area deduced. Obviously this is approximately equal to
half the surface of the hand.
Fig. 229. — Bottle
arranged for
Water-Valve.
CHAPTER XIII
THE PHYSIOLOGY OF THE CONTRACTILE TISSUES
SECTION I. — PRELIMINARY OBSERVATIONS — PHYSICAL AND
TECHNICAL DATA.
IN all the great functions of the body muscular movements play
an essential part. The circulation and the respiration, the two
functions most immediately essential to life, are kept up by the
contraction and relaxation of muscles. The movements of the
digestive canal, the regulation of the blood-supply to its glands and
to all parts of the body, and that immense class of movements
which we call voluntary, are all dependent upon muscular action,
which, again, is indebted for its initiation, continuance, or control,
to impulses passing along the nerves from the nerve-centres.
Hitherto we have not gone below the surface fact, that muscular
fibres have the power of contracting, either automatically, or in
response to suitable stimuli. In this chapter and the two next we
shall consider in detail the general properties of muscle, nerve, and
the other excitable 'tissues.
Lying deeper than the peculiarities of individual muscles, muscular
tissue has certain common properties — physical, chemical, and
physiological. The biceps muscle flexes the arm upon the elbow,
and the triceps extends it. The external rectus rotates the eyeball
outwards. The intercostal muscles elevate the ribs. The sphincter
ani seals up by a ring-like contraction the lower end of the alimentary
canal. These actions are very different, but the muscles that carry
them out are at bottom very similar. And it cannot be doubted
that the functional differences are due entirely, or almost entirely,
to differences of anatomical connection, on the one hand with bones
and tendons, on the other with the nerve-cells of the spinal cord and
brain , The common properties in which all the skeletal muscles
agree are the subject-matter of the general physiology of striated
muscle.
The cardiac muscle differs more, both in structure and in function,
from the skeletal muscles than these do among themselves; the
smooth muscle of the intestines and bloodvessels still more. But
every muscular fibre, striped or unstriped, resembles every other
723
THE PHYSIOLOGY OF THE CONTRACTILE TISSUES
muscular fibre more than it does a nerve- fibre or a gland-cell or an
epithelial scale. The properties common to all muscle make up the
general physiology of muscular tissue.
A nerve-fibre is at first sight very different from a muscular fibre.
It has diverged more widely from the primitive type of undiffer-
entiated protoplasm, but.it retains, in common with the muscle-
fibre, susceptibility to stimulation, or excitability, the capacity for
growth, and to a limited extent the capacity for reproduction ; and
while it has lost the power of contraction or contractility, it has
developed in a higher degree than any other tissue the power of
conducting the excited state. This inheritance of primitive pro-
perties, retained aliko by both tissues, is the basis of the general
physiology of muscle and nerve.
The electrical organ of Torpedo or Malapterurus is inter-
mediate in some respects between muscle and nerve, and has
properties common to both. In the gland-cell the chemical powers
of native protoplasm have been specialized and developed. Con-
tractility has been, in general, entirely lost ; but excitability remains.
The idea that certain common en-
dowments find expression in the
action of muscle, nerve, electrical
organ, gland, etc., in the midst
of all their apparent differences, is
the basis of the general physiology
of the excitable tissues.
It is impossible to understand the
general physiology of muscle and
nerve without some acquaintance
with electricity. It would be out of
place to give even a complete sketch
of this preliminary but essential
knowledge here; and the student is expressly warned that in this book
the elementary facts and principles of physics are assumed to be part
of his mental outfit. But in describing some of the electrical apparatus
most commonly used in the study of this portion of our subject, and
which are employed in the Practical Exercises, it may be useful to recall
some of the physical facts involved.
Batteries. — The Daniell cell is perhaps better suited for physiological
work than any other voltaic element, although for special purposes
Grove, Leclanche, bichromate of potassium or dry batteries may be
employed (p. 197). Storage batteries or current from the street supply
may also be used.
Inside the Daniell cell the current (the positive electricity) passes
from zinc to copper; outside, from copper to zinc. The copper is called
the positive, the zinc the negative, pole. When the current is passed
through a tissue, the electrode by which it enters is termed the anode,
and that by which it leaves the tissue the kathode. The anode is,
therefore, the electrode connected with the copper of the Daniell's cell;
the kathode is connected with the zinc.
Potential — Current Strength — Resistance. — We do not know what
in reality electricity is, but we do know that when a current flows along
Fig. 230. — Daniell Cell. A, outer vessel;
B, copper; C, porous pot; D, zinc rod;
D is supposed to be raised a little so as
to be seen.
PRELIMINARY DATA 725
a wire energy is expended, just as energy is expended when water flows
from a higher to a lower level. Many of the phenomena of current
electricity can, in fact, be illustrated by the laws of flow of an incom-
pressible liquid. The difference of level, in virtue of which the flow
of liquid is maintained, corresponds to the difference of electrical level,
or potential, in virtue of which an electrical current is kept up. The
positive pole of a voltaic cell is at a higher potential than the negative.
When they are connected by a conductor, a flow of electricity takes
place, which, if the difference of level or potential were not constantly
restored, would soon equalize it, and the current would cease; just as
the flow of water from a reservoir would ultimately stop if it was not
replenished. If the reservoir was small, and the discharging-pipe large,
the flow would only last a short time ; but if water was constantly being
pumped up into it, the flow would go on indefinitely. This is prac-
tically the case in the Daniell cell. Zinc is constantly being dissolved,
and the chemical energy which thus disappears goes to maintain a
constant difference of potential between the poles. Electricity, so to
speak, is continually running down from the place of higher to the place
of lower potential, but the cistern is always kept full.
The difference of electrical potential between two points is called
the electromotive force; and from its analogy with difference of pressure
in a liquid, it is easy to understand that the intensity or strength of the
current — that is, the rate of flow of the electricity between two points of
a conductor — does not depend upon the electromotive force alone,
any more than the rate of discharge of water from the end of a long-
pipe depends alonfe on the difference of level between it and the reser-
voir. In both cases the resistance to the flow must also be taken account
of. With a given difference of level, more water will pass per second
through a wide than through a narrow pipe, for the resistance due to
friction is greater in the latter. In the case of an electrical current, a
wire connecting the two poles of a Daniell's cell will represent the pipe.
A thick short wire has less resistance than a thin long wire; and for a
given difference of potential, of electric level, a stronger current will
flow along the former. But for a wire of given dimensions, the in-
tensity of the current will vary with the electromotive force. The
relation between electromotive force, strength of current, and resistance
17
were experimentally determined by Ohm, and the formula C= ~ »
which expresses it, is called Ohm's Law. It states that the current
varies directly as the electromotive force, and inversely as the resist-
ance.
For the measurement of electrical quantities a system of units is
necessary. The common unit of resistance is the ohm, of current
the ampdre, of electromotive force the volt. The electromotive force
of a Daniell's cell is about a volt. An electromotive force of a volt,"
acting through a resistance of an ohm, yields a current of one ampere.
But the current produced by a Daniell's cell, with its poles connected
by a wire of i ohm resistance, would be less than an ampere, because
the internal resistance of the cell itself — that is, the resistance of the
liquids between the zinc and the copper — must be added to the external
resistance in order to get the total resistance, which is the quantity
represented by R in Ohm's Law.
Measurement of Resistance. — To find the resistance of a conductor,
we compare it with known resistances, as a grocer finds the weight of a
packet of tea by comparing it with known weights. The Wheatstone's
bridge method of measuring resistance depends on the fact that if four
resistances, AB, AD, BC, CD, are connected, as in Fig. 231, with each
726 THE PHYSIOLOGY OF 711 L CONTRACTILE TISSUES
other, and with a galvanometer. G, and a battery, F, no current will
A T$ 'R'"*
flow through the galvanometer \\lien YTS=QFJ-
In making the measurement, a resistance box, containing a large
number of coils of wire of different resistances, is used. The resistances
corresponding to AB and AD may be made equal, or
may stand to each other in a ratio of i : 10, i : 100,
etc. Then, the unknown resistance being CD, BC
is adjusted by taking plugs out of the box till, on
closing the current, there is either no deflection, or the
deflection is as small as it is possible to make it with
the given arrangement.
Galvanometers. — A galvanometer is an instrument
used to detect a current, to determine its direction,
and to measure its intensity. Since, by Ohm's law,
electromotive force, resistance, and current strength
are connected together, any one of them may be
measured by the galvanometer. A galvanometer of
Fig. 231. Wheat- the kind ordinarily used in physiology consists essen-
stone s Bridge, tially of a small magnet suspended in the axis of a
coil of wire, and free to rotate under the influence
of a current passing through the coil. The most sensitive instruments
possess a small mirror, to which the magnet is rigidly attached. A ray
of light is allowed to fall on the mirror, from which it is reflected on
to a scale ; and the
rotation oi the mir-
ror is magnified and
measured by the ex-
cursion of the spot
of light on the scale.
The method of read-
ing by a telescope
can be applied to any
mirror galvanometer, B
and is often extreme-
ly convenient in
physiological work.
Sometimes a small
scale is fastened on
the mirror itself, and
o'bserved directly
through a low-power
microscope.
Fig. 232. — Diagram of String Galvanometer. The string or fibre CC is stretched be-
tween the poles of a powerful electromagnet. When a current passes down the
string it is deflected in the direction of the larg» arrow a — i.e., at right angles to
the magnetic field NS. When the current is reversed, the string moves in the
opposite direction. The movements of the string can be observed by a micro-
scope, A (objective E), passing through a hole bored through the centre of the
magnet poles. For obtaining records a source of light is placed at B and con-
centrated on the fibre by a condenser, F, and the movements of the shadow are
recorded by photography.
In the d'Arsonval galvanometer the current passes through a small
coil of fine wire suspended in the field of a strong magnet. When
the current passes the coil is deflected, carrying with it a small mirror
attached to the suspending filament. A great advantage of this galvano-
meter in many situations is that it is unaffected by neighbouring currents.
PRELIMINARY DATA
727
The string galvanometer of Einthoven has peculiar merits for certain
physiological purposes. It consists of a silvered quartz- or glass-fibre
stretched in a very strong magnetic field. When traversed by a current
the fibre is deflected, and by means
of a beam of light the deflection is
greatly magnified (Fig. 232).
A rheocord is an instrument by
means of which a current may be
divided, and a definite portion of it
sent through a tissue (Fig. 233).
A compensator is simply a rheo-
cord from which a branch of a current
is led off, to balance or ' compen-
sate ' any electrical difference in a
tissue, like that which gives rise to
the current of rest of a muscle, for
example (Fig. 234).
An electrometer is an instrument
for measuring electromotive force —
Fig. 233 — Diagram of Rheocord (after
Du Bois-Reymond's Model).
Fig. 234. — Compensator.
Description of Fig. 233 : 1 to VII are pieces of brass connected with the wires a to f
in such a way that, by taking out any of the brass plugs i to 5, a greater or less
resistance may be interposed between the binding-screws A and B. The two wires
a are connected by a slider s, filled with mercury or otherwise making contact between
the wires. The current from the battery B divides at A and B, part of it passing
through the rheocord, part through N, the nerve, muscle, or other conductor which
forms the alternative circuit. When a sufficient resistance R is interposed in the
chief circuit to make the total strength of the current independent of changes in the
resistance of the rheocord, the strength of the current passing through N will vary
inversely as the resistance of the rheocord. When all the plugs are in, and the slider
close up to A, there is practically no resistance in the rheocord, and all the current
passes across the brass pieces and plugs to B, and thence back to the battery. As s
is moved father away from A, the resistance of the rheocoid is increased more and
more, and the intensity of the current passing through N becomes greater and greater.
The scale S shows the length of wire interposed for any position of s, and this gives a
rough measure of the fraction of the current passing through N. When plug i or 2 is
taken out, a resistance equal to that of the two wires a is interposed; plug 3, twice
that of a ; plug 4, five times; plug 5, ten times.
Description of Fig. 234': W is a wire stretched alongside a scale S. A battery B is
connected to the binding-screws at the ends of the wire. A pair of unpolarizable
electrodes are connected, one with a slider moving on a wire, the other through a
galvanometer with one of the terminal binding-screws. In the figure a nerve is
shown on the electrodes, one of which is in contact with an uninjured portion, the
other with an injured part. The slider is moved until the twig of the compensating
current just balances the demarcation current of the nerve and the galvanometer
shows no deflection..
728 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES
that is, differences of electric potential. Lippmann's capillary elec-
trometer has been much employed in physiology. A simple form,
suitable for students working in a class where a considerable number of
copies of the instrument is needed, can be conveniently made as follows :
A glass tube is drawn out to a capillary at one end and filled with mer-
cury. The tube is inserted into a small glass bottle,* and fastened in
its neck by a cork or a plug of sealing-wax which does not quite fill the
opening, so that the interior of the bottle is still in communication with
the external air. The upper end of the tube is connected by a short
piece of rubber tubing with a glass T-tube as in Fig. 235. The bottle
is partially filled with 5 to 10 per cent, sulphuric acid, under which the
capillary dips. By means of a small reservoir made from a piece of
glass tubing filled with mercury, and connected with the stem of the
T-tube, a little mercury is forced through the capillary so as to expel
the air in it. When the pressure is lowered again, sulphuric acid is
drawn up, and now lies in the capillary in contact with the meniscus
of the mercury. A platinum wire fused through the tube, or simply
inserted through its upper end, dips into the mercury. Another,
passing through the cork, or, better, fused through the bottom of the
bottle, makes contact with the sulphuric acid through some mercury.
The bottle is fastened on the stage of a microscope, the capillary brought
into focus, and the meniscus adjusted by raising or lowering the reser-
voir. When the platinum wires are connected with points at different
potential, a current begins to pass through the instrument, and the
meniscus of the mercury in the capillary tube, where the current density
is the greatest, becomes polarized by the ions separated from the
sulphuric acid at the surface of contact between the acid and the mer-
cury, so that the meniscus is no longer in equilibrium in the tube.
The surface tension (p. 429) is diminished when the direction of the
current is from mercury to acid (mercury at a higher potential than
acid), and is no longer able to counterbalance the hydrostatic pressure
of the mercury. The meniscus therefore moves down in the tube.
With the opposite direction of current (mercury at a lower potential
than acid) the surface tension is increased, and the meniscus moves
up. The polarization develops itself almost instantaneously, and thus
an electromotive force is at once established in the opposite direction to
that between the points connected with the electrometer, and equal to
it so long as the external electromotive force is not sufficiently great to
cause continuous electrolysis of the acid — that is, so long as it is below
about 2 volts. The external current is therefore at once compensated,
and after the first moment no current passes through the instrument,
which is accordingly not a measurer of current, but of electromotive
force.
Induced Currents. — When a coil of wire in which a current is flowing
is brought up suddenly to another coil, a momentary current is developed
in the stationary coil in the opposite direction to that in the moving
coil. Similarly, if instead of one of the coils being moved a current is
sent through it, while the other coil remains at rest in its neighbour-
* A parallel-sided bottle is best, as it gives the clearest image of the menis-
cus. But it is easiest to make a cylindrical bottle from a piece of wide glass
tubing, and to insert a platinum wire into it before closing it at the bottom in
the blow-pipe flame. The tube can then be firmly fastened with sealing-wax
in a depression in a piece of wood, the wire being brought out through a
hole in the wood. Once the instrument is arranged, there is little chance
of the capillary getting broken, and there is very little evaporation of the
acid.
PRELIMINARY DATA
729
hood, a transient oppositely-directed current is set up in the latter.
When the current in the first coil is broken, a current in the same
direction is induced in the other coil.
Fig. 236.
Fig. 235. — A Simple Capillary Electrometer. B bottle containing sulphuric acid;
Hg, mercury; E,E', platinum wires. £ dips into the mercury in the vertical
tube, and E' is fused through the bottom of B, so as to make contact with the
mercury in B, the other end of it passing out through a small hole in the
wooden platform F, on which B rests. F is fastened to the stage of the
microscope S by a pin, G, passing through one of the clip-holes, and to
the wooden upright D by the pin H. D fits tightly over the microscope
stage, but can be moved laterally a little so as to bring the capillary into the
middle of the field. /, stem of glass T-tube passing through a hole in D.
L, rubber tube connecting the capillary point with the vertical portion of the
T-tube. A is a reservoir containing mercury connected by the rubber tube
M to I. A can be raised or lowered by sliding it in the clips K. C, magnified
portion of the capillary tube showing the meniscus.
Fig. 236. — Capillary Electrometer (after Frey).
Du Bois-Reymond's Sledge Inductorium (Fig, 237). — This consists of
two coils, the primary and the secondary, the former having a com-
paratively small number of turns of fairly thick copper wire, the latter
a large number of turns of thin wire. The object of this is that the
resistance of the primary, which is connected with one or more voltaic
730 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES
cells, may not cut down the current too much; while the currents
induced in the secondary, having a high electromotive force, can readily
pass through a high resistance, and are directly proportional in intensity
to the number of turns of the wire.
By means of various binding-screws and the electro -magnetic inter-
rupter or Neef 's hammer, shown in the figure and explained below it,
the current can be made once in the primary or broken once, or a con-
stant alternation of make and break can be kept up. We can thus get
a single make or break shock in the secondary, or a series of shocks,
sometimes called an interrupted or faradic current. Such a series of
stimuli can also be got by making and breaking a voltaic current at any
given rate.
A ' self -induced ' current can also be obtained from a single coil ; for
instance, from the primary coil alone of the induction apparatus. The
Fig. 237. — Du Bois-Reymond's Inductorium. B, primary, B', secondary, coil.
H, guides in which B' slides, with scale; D, electro-magnet; E, vibrating spring;
i, wire connecting wire of D to end of primary; v, screw with platinum point,
connected with other end of primary ; A, A', binding-screws, to which are attached
the wires from battery. A' is connected with the wire of the electro-magnet D;
and through it and t with the primary.
reason of this is, that when a current begins to flow through any turn
of a coil of wire it induces in all the other turns a current in the opposite
direction, and, when it ceases to flow, a current in the same direction
as itself. The former current, ' the make extra shock,' being in the
opposite direction to the inducing current, is retarded in its develop-
ment, and reaches its maximum more slowly than ' the break extra
shock.' But, as we shall see, the suddenness with which an electrical
change is brought about is one of the most important factors in elec-
trical stimulation, and therefore the break extra shock is a much more
powerful stimulus than the make. Owing to these self-induced cur-
rents, the stimulating power of a voltaic stream may be much in-
creased by putting into the circuit a coil of wire of not too great
reristance.
The self-induction of the primary also affects the stimulating power
of the currents induced in the secondary; the shock induced in the
secondary by break of the primary current is a stronger stimulus than
that caused at make of the primary. The reason is that with a given
distance of primary and secondary, and a given intensity of the voltaic
current in the primary, the abruptness with which the induced current
PRELIMINARY &ATA
73»
in the secondary is developed depends upon the rapidity with which the
primary current reaches its maximum at closing, or its minimum (zero)
at opening. Now, the make extra current retards the development of
the primary current, while in the opened circuit of the primary coil the
current intensity falls at once to zero.
The inequality between the make and break shocks of the secondary
coil can be greatly reduced by means of Helmholtz's wire. Connect one
pole of the battery with v (Fig. 237), and the other with A'. Join A
and A' by a short, thick wire. With this arrangement the primary cir-
cuit is never opened, but the current is alternately allowed to flow
through the primary, and short-circuited when the spring touches v.
The ' make ' now corresponds to the sudden increase of intensity of
the current in the primary when the short-circuit is removed, and the
' break ' to its sudden decrease when the short-circuit is established.
In both cases self-induced currents are developed, and therefore both
shocks are weakened. But the opening stimulus is now slightly the
weaker of the two, because the opening extra shock has to pass through
a smaller resistance (the short-circuit) than the closing extra shock
(which passes by the battery), and therefore opposes the decline of
current intensity on short-circuiting more than the closing shock
opposes the increase of
current intensity on long-
circuiting through the
primary.
By means of wires con-
nected with the terminals
of the secondary coil,
and leading to electrodes,
a nerve or muscle may
be stimulated . It is usual
to connect the wires to
a short - circuiting key
(Fig. 240), by opening
which the induced current is thrown
lated. For some purposes
Fig. 238. — Unpolarizable Electrodes. A. hook-
shaped; B, U -tubes; C, straight; D, clay in
contact with tissue; S, saturated zinc sulphate
solution ; Z, amalgamated zinc wire.
into the tissue to be stimu-
the electrodes may be of platinum;
but all metals in contact with moist tissues become polarized when
currents pass through them — that is, have decomposition products of
the electrolysis of the, tissues deposited on them. And as any slight
chemical difference, or even perhaps a difference of physical state, be-
tween the two electrodes will cause them and the tissues to form a
battery evolving a continuous current, it is often desirable to use un-
polarizable electrodes.
Unpolarizable Electrodes. — Some convenient forms of these are
represented in Fig. 238. A piece of amalgamated zinc wire dips into
saturated zinc sulphate solution contained in the upper part of a glass
tube. The lower end of the tube may be straight, but drawn out so
as to terminate in a not very large opening, or it may be bent into a
hook, in the bend of which a hole is made. Before the tube is filled
with the zinc sulphate solution, the lower part of it is plugged with
china clay made up with physiological salt solution. The clay just
projects through the opening, and thus comes in contact with the
tissue. When these electrodes are properly set up, there is very little
polarization for several hours, but for long experiments, U-shaped
tubes, filled with saturated zinc sulphate solution, are better. The
amalgamated zinc dips into one limb, and a small glass tube filled with
clay, on which the tissue is laid, into the other.
732
Pohl's Commutator or Reverser (Fig. 239) consists of a block of paraf-
fin or wood with six mercury cups, each in connection with a binding-
screw (not shown in the figure). Cups i and 6 and 2 and 5 are connected
by copper wires, which cross each other without touching. The bridge
consists of a glass or vulcanite cross-piece a, to which are attached two
wires bent into semicircles, each connected with a straight wire dip-
ping into the cups 3 and 4 respectively. With the bridge in the posi-
tion shown in the figure, a current coming in at 4 would pass out by
the wire connected with i, and back again by that connected with 2, in
the direction shown by the arrows. When the bridge is rocked to the
other side so that the bent wires dip into 5 and 6, the direction of the
current is reversed. The cross-wires may be taken out altogether, and
the commutator used to send a current at will through either of two
circuits, one connected with i and 2, and the other with 5 and 6.
Du Bois -Reymond's Short-
circuiting Key. — A cheap and
convenient form is shown in
Fig. 240.
Time - Markers — Electric Sig-
nal.— It is of importance to know
the time relations of many
physiological phenomena which
are graphically recorded ; for
Fig. 239.— Pohl's Commutator.
Fig. 240. — Short-Circuiting Key.
example, the contraction of a skeletal muscle or the beat of a heart.
For this purpose a tracing showing the speed, of the travelling sur-
face in a given time is often taken simultaneously with the record
of the movement under investigation. For a slowly-moving surface
it is sufficient to mark intervals of one or two seconds, and this is
very readily done by connecting an electro-magnetic marker (such
as the electric signal of Deprez) with a circuit which is closed and
broken by the seconds pendulum of an ordinary clock or a metronome
(Fig. 88, p. 195). Special clocks have also been constructed which
permit of the time intervals being varied. For shorter intervals a
tuning-fork is used, which makes and breaks a circuit including an
electromagnetic marker, or writes on the drum directly by means of
a writing-point attached to one of the prongs.
Amoeboid movement (p. 16) is the most primitive, the least
elaborated form of contraction. The maximum velocity of the
movement has been reckoned at o-ooS millimetre a second. Stimu-
CILIA 733
lation with the constant current or induction shocks causes the
whole of the pseudopodia to be drawn in. This illustrates a
universal property of protoplasm, excitability, or the power of re
sponding to certain influences, or stimuli, by manifestations of the
peculiar kind which we distinguish as vital or physiological. Many
unicellular organisms and the chief varieties of the white blood-
corpuscles possess the power of amoeboid movement ; and we have
already dwelt upon some of the important functions fulfilled by
such movement in the higher animals and in man. A great dis-
tinction between this kind of contraction and that of a muscular
fibre is that it takes place in any direction.
Cilia. — Cilia possess a higher and more specialized grade of
contractility. They are very widely distributed in the animal
kingdom; and analogous structures are also found in many low
plants, such as the motile bacteria.
In the human subject ciliated epithelium usually consists of
several layers of cells, the most superficial of which are pear-shaped,
the broad end being next the surface, and covered with extremely
fine processes, or cilia, about 8 fj, in length, which are planted on
a clear band. It lines the respiratory passages, the middle ear and
Eustachian tube, the Fallopian tubes, the uterus above the middle
of the cervix, the epididymis, where the cilia are extremely long,
and the central cavity of the brain and spinal cord.
Ciliary motion can be readily studied by placing a scraping from
the palate of a frog or a small portion of a gill of a fresh-water mussel
under the microscope in a drop of physiological salt solution. The
motion of the cilia is at first so rapid that it is impossible to make
out much, except that a stream of liquid, recognized by the solid
particles in it, is seen to be driven by them in a constant direction
along the ciliated edge. When the motion has become less quick,
which it soon does if the tissue is deprived of oxygen, it is seen to
consist in a swift bending of the cilia in the direction of the stream,
followed by a slower recoil to the original position, which is not at
right angles to the surface, but sloping streamwards. All the cilia
on a tract of cells do not move at the same time ; the motion spreads
from cell to cell in a regular wave. The energy of ciliary motion
may be considerable, although far inferior to that of muscular con-
traction. The work which cilia are capable of performing can be
calculated by removing the membrane, fixing it on a plate of glass,
cilia outwards, putting weights on the glass plate, and allowing the
cilia, like an immense number of feet, to carry it up an inclined plane.
Bowditeh found in this way that the cilia on a square centimetre of
mucous membrane did nearly 7 gramme-millimetres of work per
minute (equal to the raising of 7 grammes to a height of a milli-
metre).
734 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES
Since the cilia in the respiratory tract all lash upwards, they
must play an important part in carrying up foreign particles taken
in with the air, and the mucus in which
they are entangled, as well as patho-
logical products. Engelmann found
that the energy of ciliary motion in-
creases as the temperature is raised
up to about 40° C., after which it
Fig. 241— Ciliated Cell (M.
Heidenhain). From a
' liver duct ' of the garden
snail x 2,500.
Fig. 242. — Ciliated Cell (Schneider).
From a flatworm (Planocera folium).
i, space between two adjoining
ciliated cells; 2, basal bodies; 4,
inner granule; 5, 'cilia roots';
6, boundary layer.
diminishes quickly. Over-heating causes cilia to come to rest, but
if the temperature has not been too high, and has not acted too
long, they recover on cooling, thus exhibiting the phenomena of
heat standstill which we have already studied in the heart.
It is not well understood in what way the contraction of the cilia
depends upon their connection with the body of the ciliated cell. Very
few cases occur in which cilia have the power of independent motion
when severed from the cell-body. It has been observed in certain low
forms of animals that cilia which have been broken off from the cell
are still able to contract when a small portion of the substance of the
cell-body at the point where the cilium is attached to the cell, the
so-called basal piece, or basal body (Fig. 242), has come off along with
them. In other forms isolated cilia can contract in the absence of
anything corresponding to the basal piece. It cannot, therefore, be
said that continuity with the basal piece is absolutely necessary. Nor
is it known what significance for the ciliary movements is possessed
by the long fibrillse, called the ' roots of the cilia,' which in some animals
PHYSICAL PROPERTIES OF MUSCLE 735
run down through the cell from the basal bodies (Figs. 241, 242). In
some worms and molluscs ciliated cells are supplied with nerve-fibres,
but this has not been demonstrated for the higher animals.
SECTION II. — PHYSICAL PROPERTIES AND STIMULATION OF MUSCLE.
Since most of our knowledge of the general physiology of muscle
has been gained from striped muscle, in what follows we always
refer to ordinary skeletal muscle, unless it is otherwise stated.
The sartorius and the gastrocnemius are the classical objects for
experiments on striated muscle. For smooth muscle the adductor
muscle of Anodon, the fresh-water mussel, a ring cut from the middle
portion of the frog's stomach, the rabbit's ureter and uterus, and
the cat's bladder, have been most used.
Physical Properties of Muscle — Elasticity. — All bodies may have their
shape or volume altered by the application of force. Some require a
large force, others a small force, to produce a sensible amount of dis-
tortion. The elasticity of a body is the property in virtue of which it
tends to recover its original form or bulk when these have been altered.
Liquids and gases have only elasticity of volume; solids have also
elasticity of form. Most solids recover perfectly, or almost perfectly,
from a slight deformation. The limits of distortion within which this
occurs are called the limits of elasticity, and they vary greatly for
different substances. Living muscle has very wide limits of elasticity;
it may be deformed — stretched, for example — to a very considerable
extent, and yet recover its original length when the stretching force
ceases to act.
The extensibility of a body is measured by the ratio of the increase
of length, produced by unit stretching force per unit of area of the
cross-section, to the original length of a uniform rod of the substance.
Is
If e is the extensibility, e= =-=> where / is the increase of length,
L the original length, 5 the cross-section, and F the stretching force.
Suppose we wish to compare the extensibility of two substances.
Let A and B be strips or rods of the substances, the length of A being
500 mm., that of B 1,000 mm.; the cross-section of A, 100 sq. mm., of
B, 200 sq. mm. Let the elongation produced by a weight of i kilo
be 10 mm. in each, then the extensibility of A is — — = 2 ; and that
500 x i
10 x 200
of B is - — = 2; that is, the substances are equally extensible.
. 1,000 x i
Young's modulus of elasticity, or the coefficient of elasticity, is the
quotient of the deforming force acting on unit area of the given body
by the deformation produced (within the limits of elasticity). In the
"pj T f?
above example it is — -*-?-• that is, -=—, the reciprocal of the extensi-
bility e. For steel the coefficient of elasticity is very large, for muscle
small. Or, as we may otherwise express it, living muscle within its
limits of elasticity is very extensible ; a small force per unit area of
cross-section of a prism of it will produce a comparatively great elonga-
tion. The extensibility, however, diminishes continually with the
elongation, so that equal increments of stretching force produce always
736 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES
less and less extension. If, for instance, the sartorious or semi-mem-
branosus of a frog be connected with a lever writing on a blackened
surface, and weights increasing by equal amounts be successively
attached to it, the recording surface being allowed to move the same
distance after the addition of each weight, a series of vertical lines,
representing the amount of each elongation, will be traced. When the
lower ends of all the vertical lines are joined, a smooth curve with the
concavity upwards is obtained (Fig. 243). This is a property common
to living and dead muscle and to other animal structures, such as
arteries. Marey's method, in which the weight is continuously in-
creased from zero and then continuously decreased to zero again by
the flow of mercury into and out of a vessel attached to the muscle,
gives directly the curve of extensibility.
The elongation of a steel rod or other
inorganic solid is proportional within
limits to the extending force per unit of
cross-section ; and a curve plotted with the
weights for abscissae and the amounts of
elongation for ordinates would be a straight
line. But this is not a fundamental dis-
tinction between animal tissues, and the
materials of unorganized nature, as some
writers seem to suppose. For when the
slow after-elongation which follows the
first rapid increase in length in the loaded,
243 — Curves of Extensi- excised muscle is waited for, the curve of
bility. M, of muscle; S, of an extensibility comes out a straight line
ordinary inorganic solid. (Wundt), and within limits this is also the
case for human muscles in the intact body.
And although a steel rod much more quickly reaches its maximum
elongation for a given weight when loaded, and its original length when
the weight is removed, than does a muscle, time is required in both cases,
and the difference is one of degree rather than of kind. When muscle
(striated or smooth) is not stretched beyond the limit of physiological
relaxation, the amount of stretching is proportional to the weight, and
the same is true of all the simple tissues of the body (Haycraft).
Dead muscle is less extensible than living, and its limits of elasticity
are much narrower. In the state of contraction the extensibility is
increased in excised frog's muscle. When fatigue comes on after many
excitations, the after-elongation becomes more pronounced, but the
return after unloading is very incomplete. Donders and Van Mans-
veldt have found that contraction causes little difference in the muscles
of a living man, although fatigue increases the extensibility.
The great extensibility and elasticity of muscle must play a con-
siderable part in determining the calibre of the vessels, and in lessening
the shocks and strains which the heart and the vascular system in
general are called upon to bear, and must contribute much to the
smoothness with which the movements of the skeleton are carried out,
and immensely reduce the risk of injury to the bones as well as to the
muscles themselves, the tendons and the other soft tissues. And not
only is smoothness gained, but economy also; for a portion of the
energy ol a sudden contraction, which, if the muscles were less ex-
tensible and elastic, might be wasted as heat in the jarring of bone
against bone at the joints, is stored up in the stretched muscle and
again given out in its elastic recoil. The skeletal muscles, too, are
even at rest kept slightly on the stretch, braced up, as it were, and
STIMULATION OF MUSCLE
737
ready to act at a moment's notice without taking in slack. This is
shown by the fact that a transverse wound in a muscle ' gapes,' the
fibres being retracted, in virtue of their elasticity, towards the fixed
points of origin and insertion. Smooth muscle, as we meet it in the
hollow viscera, is highly distensible and elastic, as is suited to organs
whose capacity is continually varying within wide limits (Fig. 244).
In the further study of muscle it is necessary first of all to consider
the means we have of calling forth a contraction — in other words, the
various kinds of stimuli.
Stimulation of Muscle. — A muscle may be excited or stimulated
either directly or through its motor nerve. It is usual to classify
stimuli as electrical, mechanical, chemical, or thermal. Electrical
stimuli are by far the most commonly employed, and will be dis-
cussed in detail. A prick, a cut, or a blow are examples of mechani-
Fig. 244. — Extensibility of Smooth Muscle (Griitzner). The upper group of four
cells (i to 4) is from a hollow organ, whose walls are contracted, and its lumen
almost abolished; the under group represents the same fibres when the organ is
full. The fibres are longer and somewhat darker. They are also displaced
somewhat along each other.
cal stimuli. The action of a fairly strong solution of common salt
or of a dilute solution of a mineral acid is usually described as
chemical stimulation. But in considering the excitation of nerve
(p. 783) we shall see that physical changes are often mixed up with
so-called chemical stimulation. The contraction caused is not a
single brief twitch, as is the case with a not too severe mechanical
excitation, but a sustained contraction or a tetanus. Sudden cooling
or heating acts as a stimulus for muscle, but thermal stimulation is
somewhat uncertain. It is not quite settled whether the contrac-
tion which can be obtained from a muscle when it is subjected to
brief local heating — to a ' thermic shock/ as some writers prefer
to say (e.g., by the momentary glow of a platinum wire below but
not touching it) — is an ordinary muscular contraction, or a physical,
although transient, contracture analogous to that caused by certain
drugs (Waller). Smooth, like striped, muscle is susceptible to
electrical, mechanical, thermal, and chemical stimulation. In
addition, in certain situations it can be excited by light (photic
stimulation), as in the case of the excised iris of fish and amphibia.
In all artificial stimulation there is an element of sudden or abrupt
change, of shock, in other words; but we cannot tell in what the
' natural ' or ' physiological ' stimulus to muscular contraction in
47
738 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES
the intact body really consists, nor how it differs from artificial
stimuli. All we know is that there must be a wide difference, and
that our methods of excitation must be very crude and inexact
imitations of the natural process.
Direct Excitability of Muscle. — The famous controversy on the
existence of independent ' muscular irritability ' has long been
forgotten, and has no further interest except for the antiquaries of
science, if such exist. The direct excitability of muscle in the modern
sense is not quite the same as the ' muscular irritability/ the dis-
cussion of which occupied Haller and his contemporaries. What
the modern physiologists have been called upon to decide is whether
muscular fibres can be caused to contract except by an excitation
that reaches them through their nerves. In this sense there can
exist no doubt that muscle is directly excitable, and some of the
proofs are as follows:
(i) The ends of the frog's sartorius contain no nerves, yet they
respond to direct stimulation. (2) Certain chemical stimuli —
ammonia, for instance — excite muscle but not nerve. (3) When
the motor nerves of a limb are cut they degenerate, and after a
certain time stimulation of the nerve-trunk causes no muscular
contraction, while the muscles, although atrophied, can be made
to contract by direct stimulation. (4) Finally, there is the cele-
brated curara experiment of Claude Bernard, which is described in
a somewhat modified form in the Practical Exercises, p. 811. A
ligature is tied firmly round one thigh of a frog, omitting the sciatic
nerve; then curara is injected, and in a short time the skeletal
muscles are paralyzed. That the seat of the paralysis is not the
contractile substance of the muscles itself is shown by their vigorous
response to direct stimulation. The ' block ' is not in the nerve-
trunk, nor above it in the central nervous system, for the ligated
leg is often drawn up — that is, its muscles are contracted — although
the poison has circulated freely in the sacral plexus and the spinal
cord. Further, if the nerve of the ligated leg be prepared as high
up above the ligature as possible, where the curara must undoubtedly
have reached it (just above the ligature the nerve has been isolated
and the circulation in it more or less interrupted), stimulation
of it will cause contraction of the muscles of the limb ; while excita-
tion of the other sciatic is ineffective.
It can be also shown, by means of the negative variation or
current of action (p. 824), that a nerve-trunk on which curara has
acted remains excitable, and capable of conducting the nerve-
impulse. The conclusion, therefore, is that the curara paralyzes
neither nerve-fibre nor the contractile substance of the muscular
fibre, but some link between the two. If the assumption be made
that the efferent medullated nerve-fibres within the muscle, since
STIMULATION OF MUSCLE 739
they are anatomically similar to those in the nerve-trunk till near
their terminations, are similarly affected by curara — and it is a
justifiable assumption — the seat of the curara paralysis must either
be the nerve-ending or some mechanism, physiological if not
anatomical, interposed between the nerve-ending and the con-
tractile substance. Now, Langley has shown that the contractions
caused by the local application of dilute nicotine solution to points
of the skeletal muscles of the frog, both in normal muscles and in
muscles whose motor nerves and nerve-endings have degenerated
after section of the nerves, are prevented by curara. He there-
Fig- 245. — -Frog's Motor Nerve-Ending (Wilson). A, B, C, three muscle-fibres. The
medullated nerve a loses its medullary sheath and breaks up on B at i. It gives
off at 2 a large non-medullated branch, which also breaks up on B. The nerve-
endings send ultraterminal fibrillae to A, B, and C, some of which were seen to
end in small knobs. A separate non-medullated nerve, n, is shown, which forms
a small plexus on B, one fibre of which penetrates to a lower plane than the other,
and ends by forming a knob under the sarcolemma.
fore concludes that, since nicotine produces its effects by a
direct action on muscle, and not by an action on nerve-endings
or on any special structure (such as the protoplasmic mass or ' sole '
at the nerve-ending in many animals) interposed between the nerve
and the muscle, no such special structure existing in the frog
(Fig. 245), curara must also act directly on the muscle. But
obviously curara does not paralyze the general contractile substance
of the muscle, else the curarized muscle would not contract on direct
stimulation. Langley accordingly assumes that, in addition to the
contractile or ' general ' substance, ' receptive ' substances exist
in the fibre, through which the excitation is tx^ansferred to the con-
tractile substance when the motor nerve is stimulated. He pictures
these receptive substances as ' side-chains ' of the contractile mole-
cule, in accordance with Ehrlich's theory of immunity (p. 31),
and distinguishes those in the neighbourhood of the nerve-ending
740 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES
from those present throughout the muscle fibre. Both the slow
local tonic contraction an4 the quick, brief conducted contractions
or twitches set up in a muscle fibre by nicotine, but especially the
latter, are much more easily elicited in that part of it which lies
under the nerve-ending than elsewhere. Indeed, the position of
the nerve-endings in the superficial fibres of a muscle can be ascer-
tained by observing the points which respond most readily to nico-
tine. Nicotine and curara, etc., are supposed to combine with the
receptive substance, which is then in both cases rendered incapable
of being affected by nerve impulses. In the case of nicotine an
additional action results from the combination with the receptive
substance — -viz., the change in the contractile substance which leads
to contraction. Curara paralyzes the transmission of the excitation
from the motor nerves to smooth muscle — the muscles of the
Fig. 246. — Tonic Contraction of Muscle during Passage of Constant Current. Two
sartorius muscles of frog connected by pelvic attachments. Current from 12
small Daniell cells in series passed through their whole length. Current closed
at m, opened at ft. Time trace, two-second intervals.
bronchi, for instance — with much greater difficulty than to ordinary
skeletal muscle, and the same is true of the inhibitory nerves of
the heart.
The action of curara gives us the means of stimulating muscle
directly; when electrical currents are sent through a non-curarized
muscle, there is in general a mixture of direct and indirect stimula-
tion, for the nerve-fibres within the muscle are also excited. Induced
currents stimulate nerve more readily than muscle. Voltaic currents
may excite a muscle whose nerves have degenerated, while induced
currents are entirely without effect.
For direct stimulation, a curarized frog's sartorius or semi-mem-
branosus is generally used on account of their long parallel fibres. For
indirect excitation, a muscle-nerve preparation, composed of a frog's
gastrocnemius with the sciatic nerve attached to it, is commonly em-
ployed, as it is easy to isolate the muscle without hurting its nerve.
STIMULATION OF MUSCLE
741
Stimulation by the Voltaic Current. — While the current continues to
pass through a nerve without any sudden or great change in its in-
tensity, there is no stimulation, and the muscle connected with the
nerve remains at rest. The same is true of striated muscle when a
weak current is passed directly through it. But in muscle the con-
stancy of the rule is more and more frequently broken by exceptional
results as the current is strengthened, a state of permanent contrac-
tion being very apt to show itself during the whole time of flow (Wundt)
(Fig. 246). Above a certain intensity of current a greater or less
degree of permanent contraction is invariably produced. This is some-
times called the ' closing tetanus.' It is, however, not a true tetanus,
but a tonic contraction, which is strongest in the neighbourhood of the
kathode, and does not spread far from it. A similar condition, the
so-called galvanotonus, is normally seen in human muscles when they or
their motor nerves are
traversed by a stream
of considerable inten-
sity. Under certain con-
ditions, too — e.g., when
a strong current is
allowed to flow for a
comparatively long time
through a muscle — the
muscle remains contrac-
ted after the opening of
the current (so-called
' opening or Hitter's tet-
anus '). Smooth muscle
is excited to contraction
even when a voltaic cur-
rent is very gradually
passed into it and slow-
ly increased, and again
when it is caused very
gradually to disappear.
But striped muscle is
not stimulated under
Fig. 2471 — Tonic Contraction during and after Flow
of Voltaic Current. Curve from frog's gastroc-
nemius. At M constant current closed, at B broken.
Contracture continues after opening of current.
Time trace, two-second intervals.
these conditions.
For nerve, and with these qualifications for muscle, too, the law
holds that the voltaic current stimulates at make and at break, but not
during its passage. Or, generalizing this a little, since it has been
shown that a sudden increase or decrease in the strength of a current
already flowing also acts as a stimulus, we may say that the voltaic
current stimulates only when its intensity is suddenly and sufficiently
increased or diminished, but not while it remains constant.*
When a strong current is closed through a muscle there is an im-
mediate sharp contraction (initial contraction). The muscle then
promptly relaxes, but incompletely. When the current is opened,
there is another contraction (Fig. 247). The force of the initial con-
traction, as measured by the resistance necessary to prevent it, is
greater than that of the tonic contraction which follows it.
A second law of great theoretical importance is that of polar stimula-
tion. At make the stimulation occurs only at the kathode ; at break only
at the anode. This is true both for muscle and nerve, but it is most
* This law of Du Bois-Reymond has been questioned by Hoorweg and others.
It seems to need modification, but the subject cannot be discussed here.
743 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES
directly and simply demonstrated on muscle. A long parallel-fibred
curarized muscle is supported about its middle; the two ends, which
hang down, are connected with levers writing on a revolving drum, and
a current is sent longitudinally through the muscle. It is not difficult
to see from the tracings that at make the lever attached to the kathodic
end moves first, and that the other lever only moves when the contrac-
tion started at the kathode has had time to reach it in its progress
along the muscle. Similarly, at break the lever connected with the
anodic end moves first. The law of polar excitation holds both for
striated and for smooth muscle. Not only is there no excitation of
unstriped muscle at the anode on closure of the current, but a previ-
ously existing contraction disappears. For skeletal muscle the make is
stronger than the break contraction. It has not been proved that this
is the case for smooth muscle.
SECTION III. — PHYSICAL AND MECHANICAL PHENOMENA OF THE
MUSCULAR CONTRACTION.
When a muscle contracts, its two points of attachment, or, if it
be isolated, its two ends, come nearer to each other; and in exact
proportion to this shortening is the increase in the average cross-
section. The contraction is essentially a change of form, not a
change of volume. The most delicate observations fail to detect
the smallest alteration in bulk (Ewald). Living fibres kept con-
tracted by successive stimuli can be examined under the microscope ;
or fibres may be ' fixed ' by reagents like osmic acid, and sometimes
a very good opportunity of studying the microscopic changes in
contraction is given by a group of fibres in which the ' fixing '
reagent has caught a wave of contraction, and, so to speak, pinned
it down. It is then seen that the process of contraction in the fibre
is a miniature of that in the anatomical muscle. The individual
fibres shorten and thicken, and the sum-total of this shortening
and thickening is the muscular contraction which we see with the
naked eye. The phenomena of the muscular contraction may
be classified thus: (i) Optical, (2) Mechanical, (3) Thermal,
(4) Chemical, (5) Sonorous, (6) Electrical. (5) will be treated under
' Voluntary Contraction ' ; (6) in Chapter XV.
(i) Optical Phenomena — Microscopic Structure of Striped Muscle. —
The structure of striped muscle has long been the enigma of histology ;
and the labours of many distinguished men have not sufficed to make
it clear. On the contrary', as investigations have multiplied, new
theories, new interpretations of what is to be seen, have multiplied in
proportion, and a resolute brevity has become the chief duty of a writer
on elementary physiology in regard to the whole question.
The muscle-fibre, the unit out of which the anatomical muscle is
built up, is surrounded by a structureless membrane, the sarcolemma.
The length and breadth of a fibre vary greatly in different situations.
The maximum length is about 4 cm. ; the breadth may be as much
as 70 /* and as little as 10 ft. When we come to analyze the muscle-
fibre and to determine out of what units it is built up, the difficulty
begins. The fibre shows alternate dim and clear transverse stripes, and
OPTICAL PHENOMENA OF MUSCULAR CONTRACTION 743
can actually be split up into discs by certain reagents. It also shows
a longitudinal striation, and can be separated into fibrils. Some have
supposed that the discs are the real structural units which, piled end
to end, make up the fibre. The fibrils they consider artificial. This
view is erroneous. It seems certain that the fibres are built up from
fibrils ranged side by side, and that the discs are artificial. The con-
tents of the muscle-fibre appear to consist of two functionally different
substances, a contractile substance, and an interstitial, perhaps nutri-
tive, non-contractile material of more fluid nature. The contractile
substance is arranged as longitudinal fibrils embedded in interfibrillar
matter (sarcoplasm). In a muscle impregnated with chloride of gold
the interfibrillar matter appears as a network.
Schafer has described the contractile elements of the muscle-fibre
(Figs. 248, 249) as fine columns (sarcostyles), divided into segments
(sarcomeres) by thin transverse
discs (Krause's membranes), occu-
pying the position of the middle of
each light stripe. Each sarcomere
contains a sarcous element la. por- ,
tion of the dark stripe) with a clear
substance at its ends, filling up the
Fig. 248. — Living Muscle of Water-
Beetle (highly magnified) (Schafer).
s, sarcolemma ; a, dim stripe ;
b, bright stripe; c, row of dots in
bright stripe, which appear to be
the enlarged ends of rod-shaped
particles, d, but in reality represent
expansions of the interstitial sub-
stance (sarcoplasm).
Fig. 249. — Portion of Leg
Muscle of Insect, treated
with Dilute Acetic Acid
(Schafer). S, sarco-
lemma; D, dot -like en-
largement of sarcoplasm;
K, Krause's membrane.
The sarcous elements
have been swollen and
dissolved by the acid.
space between the sarcous element and Krause's membrane, and con-
stituting a portion of the light stripe. The sarcous element is itself
double, and if the fibre be stretched, the two portions separate at a
line which runs transversely across the middle of the dim stripe (Hensen's
line). Schafer considers that the appearance of longitudinal fibrillation
in the sarcous elements is due to the presence in them of fine longi-
tudinal canals or pores.
The Krause's membrane of the individual fibrils is scarcely ever
visible in an intact mammalian fibre, and the apparent line in the clear
stripe of an intact fibre is an optical appearance due to interference of
light. Kuhne, who was fortunate enough to find one day a small
nematode worm moving in the interior of a fibre, saw it pass along
the fibre with perfect freedom, ignoring Krause's membrane. Possibly,
however, it was moving in the sarcoplasm, the fibrils being simply
pushed aside.
744 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES
Changes during Contraction — Theories of Contraction. — In contractions.,
according to Schafer, the clear substance between Krause's membrane
and the sarcous element passes into the canals, which are open towards
Krause's membrane, but closed towards Hensen's line. The sarcous
element therefore swells up, and the sarcomere is shortened. In the
extended muscle the clear substance leaves the pores of the sarcous
element, and accumulates in the space between it and Krause's mem-
brane. The sarcomere is thus lengthened and narrowed. While the
existence of Schafer's pores is not admitted by all observers, there is a
pretty general agreement that the sarcomere, like the cytoplasm of an
amoeboid cell, does consist of two substances, one of which (the hyalo-
plasm of the cell, the clear material of the sarcomere) interpenetrates
the other (spongioplasm of the cell, substance of the sarcous element) ;
and that in relaxation the clear fluid passes from the sarcous element
to the ends of the sarcomeres, whereas in contraction it passes in the
reverse direction into the sarcous elements. Whether the fluid passes
into and out of the meshes of an actual network, or along actual physical
pores in the sarcous element, or whether it is transferred by some
process like molecular imbibition (p. 426), need not be discussed here,
since it is not definitely known. The fundamental question by what
process the transference is determined when,, the muscle is excited also
remains unsettled. So far as is known at present, it is probable that
the mechanical energy of the contracting muscle must be derived from
the transformation of chemical energy into one of three forms : energy
associated with osmotic processes, energy associated with imbibition,
and energy associated with changes of surface tension. It is not diffi-
cult to see that a sudden increase in the osmotic concentration in the
sarcous element, due to the breaking up of large molecules or colloid
aggregates into small molecules, or the liberation of electrolytes from
the colloids, might lead to the rapid passage of water into it from
the bright bands. A sudden change of permeability of the sarcous
elements for dissolved substances in the clear fluid would have a
similar effect. The same is true of a change in their power of imbibi-
tion. But, according to Bernstein, it is scarcely to be supposed that
the extraordinarily rapid movement of water molecules which must
occur in contraction can be accounted for either by osmosis or by im-
bibition. A more plausible theory is that the surface tension — say
between the substance of the sarcous element and the clear fluid — is
altered. That the shortening of the muscle in fatigue (p. 749) and
rigor (p. 774), as well as its shortening in normal contraction, is due in
some way to the liberation of metabolic products, especially lactic acid,
is a theory of some standing, and fresh evidence in its favour has been
recently supplied. Thus it has been pointed out that the course of
heat production in the active muscle, and its relation to the time of
the mechanical response, and the development and time relations of
the electrical change which precedes that response, can be very naturally
explained on the supposition that the liberation of lactic acid on or
near some surface in the contractile substance is an essential factor in
the contraction (Mines, etc.). It is known that in the presence of acid
on the surface of certain colloid structures shortening occurs (Fischer
and Strietman).
The substance of the sarcous element which forms the dark stripe
is doubly refracting, and therefore rotates the plane of polarization,
but the clear substance of the light stripe is singly refracting. When
an uncontracted fibre is viewed with crossed nicols, the dim stripe
accordingly appears bright in the otherwise dark field. In the con-
tracted fibre the doubly refractive material remains in the stripe which
MECHANICAL PHENOMENA OF MUSCULAR CONTRACTION 745
is dim in ordinary light. There is no transference of it, but, according
to most writers, the bands which are dim in ordinary light increase in
size by the transference of liquid from the isotropous band.
Diffraction Spectrum of Muscle. — When a beam of white light passes
through a striped muscle, it is broken up into its constituent colours,
and a series of diffraction spectra are produced, just as happens when
the light passes through a diffraction grating (a piece of glass on which
are ruled a number of fine parallel equidistant lines). The nearer the
lines are to each other, the greater is the displacement of a ray of light
of any given wave-length. It has accordingJy been found that when ?,
muscular fibre contracts, the amount of displacement of the diffraction
spectra increases. At the same time the whole fibre becomes more
transparent.
(2) Mechanical Phenomena. — The muscular contraction may be
graphically recorded by connecting a muscle with a lever which is
moved either by its shortening or by its thickening. The lever writes
on a blackened surface, which must
travel a.t a uniform rate if the form
and time-relations of the muscle
curve are to be studied, but may be
at rest if only the height of the con-
traction is to be recorded. The whole
arrangement for taking a muscle-
tracing is called a myograph (Fig.
287, p. 812). The duration of a
' twitch ' or single contraction (in-
cluding the relaxation) of a frog's
muscle is usually given as about
one-tenth of a second, but it may
vary considerably with temperature,
fatigue, and other circumstances.
It is measured by the vibrations of
a tuning-fork written immediately
below or above the muscle curve.
When the muscle is only slightly
weighted, it but very gradually
reaches its original length after con-
traction, a period of rapid relaxation
being followed by a period of ' resi-
dual contraction,' during which the
descent of the lever towards the base-line becomes slower and slower,
or stops altogether some distance above it. The duration of the con-
traction of smooth muscle evoked by a single momentary stimulus is
much greater than that of striped muscle (two to seven seconds for the
rabbit's ureter; five to fifteen seconds for the cat's nictitating mem-
brane; one to two minutes for the frog's stomach).
Latent Period. — If the time of stimulation is marked on the tracing,
it is found that the contraction does not begin simultaneously with it,
but only after a certain interval, which is called the latent period.
This can be measured by means of the spring myograph (Fig. 251)
or of the pendulum myograph, a pendulum which in its swing carries
a smoked plate against the writing-point of a lever connected with a
muscle. The carrier of the recording plate opens, at a definite point
in its passage, a key in the primary coil of an induction machine, and
so causes a shock to be sent through the muscle or nerve, which is con-
nected with the secondary. The precise point at which the stimulus
is thrown in can be marked on the tracing by carefully bringing the
Fig. 250. — Living Muscular Fibre (from
Geolrupes stercorarius). i, in or-
dinary; 2, in polarized light. (Van
Gehuchten.) In living muscle (at
least in fibres which are not extended)
in contrast to dead muscle after treat-
ment with reagents, the doubly re-
fracting or anisotropous substance is
present in the greater part of the fibre ;
and with crossed nicols the position of
the singly refracting or isotropous
material is indicated only by narrow
transverse black lines or rows of dark
dots.
745
plate to the position in which the key is just opened, and allowing
the lever to trace here a vertical line (or, rather, an arc of a circle).
The portion of the time-tracing between this line and a parallel line
drawn through the point at which the contraction begins gives the
latent period.
Helmholtz measured the length of the latent period by means of the
principle of Pouillet, that the deflection of a magnet by a current of
given strength and of very short duration is proportional to the time
during which the current acts on the magnet. He arranged that at
the moment of stimulation of the muscle a current should be sent
through a galvanometer, and should be broken by the contraction of
the muscle the moment it began. In this way he obtained the value
of Y^JJ second for the latent period of frog's muscle. The tendency of
ILL
Fig. 251. — Spring Myograph. A, B, iron uprights, between which are stretched the
guide-wires on which the travelling plate a runs; k, pieces of cork on the guides
to gradually check the plate at the end of its excursion, and prevent jarring;
b, spring, the release of which shoots the plate along; A, trigger-key, which is
opened by the pin d on the frame of the plate.
later observations has been to make the latent period shorter. Burdon
Sanderson found that the change of form begins in unweighted or very
slightly weighted muscle with direct stimulation in y^y second after,
and the electrical change (p. 824) simultaneously with, the excitation.
It is known that the apparent latent period depends upon the resistance
which the muscle has to overcome in beginning its contraction.
The maximum shortening, or ' height of the lift,' depends upon the
length of the muscle, the direction of the fibres, the strength of the
stimulus, the excitability of the tissue, and the load it has to raise.
In a long muscle, other things being equal, the absolute shortening,
and therefore the maximum height of the curve, will be greater than
in a short muscle; in a muscle with fibres parallel to its length — the
sartorius, for instance — it will be greater than in a muscle like the
gastrocnemius, with the fibres directed at various angles to the long
axis. For stimuli less than maximal, the absolute contraction increases
MECHANICAL PHENOMENA OF MUSCULAR CONTRACTION 7*7
with the strength of stimulation, and a given stimulus will cause a
greater contraction in a muscle with a given excitability than in a
muscle which is less excitable. Under ordinary experimental condi-
tions ,vt least, weak stimuli cause a smaller contraction than strong,
not only because each stimulated fibre contracts less, but because a
smaller number of fibres are excited (p. 155). The objects used for the
study of muscular contraction contain many fibres, and it is not in
Fig. 252. — Curve of a Single Muscular Contraction or Twitch taken on Smoked Glass
with Spring Myograph and photographed. Vertical Jine A rr.arks the point at
which the muscle was stimulated; time tracing shows t$-(7 of a second (reduced).
general possible to distribute the stimulus equally to all. This is true
for smooth muscle as well as for striped. Finally, increase of the load
per unit of cross-section of the muscle diminishes above a certain limit
the ' height of the lift.'
Influences which affect the Time-Relations of the Muscular Contrac-
tion.— Many circumstances affect the form of the muscle curve and its
time-relations .
(a) Influence of the Load — Isotonic and Isometric Contraction. — The
first effect of contraction is to suddenly stretch the muscle, and the
more the muscle is loaded the greater will this
elongation be. So that at the beginning of the
actual shortening part of the energy of contraction
is already expended without visible effect, and has
to be recovered from the elastic reaction during
the ascent of the lever.
The contraction of a muscle loaded by a weight
which is not increased or diminished during the
contraction is said to be isotonic, for here the
tension of the muscle is the same throughout, and
its length alters . When the muscle is attached very
near the fulcrum of the lever, so that it acts upon
a short arm, while the long arm carrying the
writing-point is prevented from moving much by
a spring, the muscle can only shorten itself very
slightly; but the changes of tension in it will be
related to those in the spring, and therefore to the
curve traced by the writing-point. Such a curve
is called isometric, since the length of the muscle
remains almost unaltered. In the body muscles
usually contract under conditions more nearly
allied to those of the isometric than to those of
the isotonic contraction.
The work done by a muscle in raising a weight is equal to the product
of the weight by the height to which it is raised. Beginning with no
load at all, it is found that the weight can be increased up to a certain
limit without diminishing the height of the contraction; perhaps the
height may even increase. Up to this limit, then, the work evidently
increases with the load. If the weight is made still greater, the con-
Fig. 253. — Contrac-
tions ol Smooth Mus-
cle: Cat's Bladder
(C. C. Stewart).
Stimulated with pro-
gressively stronger
induction shocks.
The lowest line is the
time trace (lo-second
intervals). Immedi-
ately below the mus-
cular contractions are
marked the points at
which the stimuli
were thrown in.
748 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES
traction becomes less and less, but up to another limit the increase oi
weight more than compensates for the diminution of ' lift,' and the
work still increases. Beyond this, further increase of weight can no
Fig. 254. — Influence of Load on the Form of the Muscle Curve, i. curve taken with
unloaded lever; 2, 3, 4, weight successively increased; 5. abscissa line: time trace,
•jfaf second (reduced).
longer make up for the lessening of the lift, and the work falls off till
ultimately the muscle is unable to raise the weight at all.
The ' absolute contractile force ' of an active muscle may be measured
by determining the weight which, brought to bear upon the muscle at
Fig. 255. — Influence of Temperature on the Striated Muscle Curve. 2, air tempera-
ture; i. 25° — 30° C. ; 3, 7° — 10° C. ; 4, ice in contact with muscle. The fifth curve
was taken at a little above air temperature.
the instant of contraction, is just able to prevent shortening without
stretching the muscle. It, of course, depends, among other things, on
the cross-section of the muscle. During the contraction the absolute
force diminishes continually, so that a smaller and smaller weight is
MECHANICAL PHENOMENA OF MUSCULAR CONTRACTION 749
sufficient to stop any further contraction the more the muscle has
already shortened before it is applied. At the maximum of the con-
traction the absolute force is zero. Hence a muscle works under the
most favourable conditions when the weight decreases as it is raised,
and this is the case with many of the muscles of the body. During
flexure of the forearm on the elbow, with the upper arm horizontal, a
weight in the hand is felt less and less as it is raised, since its moment,
which is proportional to its distance from a vertical line drawn through
the lower end of the humerus, continually diminishes.
(b) Influence of Temperature on the Muscular Contraction. — Increase
of temperature of the muscle up to a certain limit diminishes the latent
period and the length of the curve, and increases
the height of the contraction, but beyond this limit
the contractions are lessened in height (Fig. 255).
Marked diminution of temperature causes, in
general, an increase in the latent period and length,
and a decrease in the height of the contraction. In
the heart the effect of cold in strengthening the
beat is often very marked. Temperature affects
the contraction curve of smooth muscle much in the
same way as that of striated muscle (Fig. 256).
(c) Influence of Previous Stimulation — Fatigue.
—If a muscle is stimulated by a series of equal
shocks thrown in at regular intervals, and the
contractions recorded, it is seen that at first
each curve overtops its prede-
cessor by a small amount.* This
phenomenon, which is regularly
_ observed in fresh skeletal muscle
Fig. 256. — Influence of Temperature on the Smooth Muscle Curve: Cat's Bladder
(C. C. Stewart). Contractions at different temperatures with the same strength
of stimulus. The temperatures (Centigrade) are marked on the curves.
(Fig. 260), although it was at one time supposed to be peculiarly a
property of the muscle of the heart (Fig. 261), is called the staircase,'
and seems to indicate that within limits the muscle is benefited by
contraction and its excitability increased for a new stimulus. Soon,
however, in an isolated preparation, the contractions begin to decline
in height, till the muscle is at length utterly exhausted, and reacts
no longer to even the strongest stimulation (Figs. 258, 259, 288).
A conspicuous feature of the contraction-curves of fatigued
muscle is the progressive lengthening, which is much more marked
in the descending than in the ascending periods; in other words,
* Guthrie has recently described an interesting series of phenomena illus-
trating the influence of previous stimulation on the irritability of muscle.
Under given conditions, for example, strong stimulation increases the response
of skeletal muscles to subsequent single stimuli, it may be, by hundreds per
cent.
75o THE PHYSIOLOGY OF THE CONTRACTILE TISSUES
relaxation becomes more and more difficult and imperfect (Fig. 288,
p. 814). In smooth muscle (cat's bladder or ring from frog's stomach)
fatigue can be very easily demon-
strated in the same way, and the
curves present similar features, with
the exception that, instead of be-
coming longer in fatigue, the suc-
cessive contractions become shorter.
It is by no means so easy to
fatigue a muscle still in connection
with the circulation as an isolated
muscle. But even the latter, if left
to itself, will to some extent re-
cover, and be again able to con-
tract, although exhaustion is now
more readily induced than at first.
Fig. 258. — Fatigue Curve of Muscle-.
Frog's Gastrocnemius. The arrange-
ment with which the curve figured
was obtained was a so-called auto-
matic muscle interrupter (Fig. 257).
A wire on the lever is made to close
and open the primary circuit of an
inductorium, the muscle or nerve
being connected with the secondary.
Every time the needle touches the
mercury the muscle is stimulated
automatically.
A'
Fig. 257. — Automatic Muscle Interrupter.
K. battery; P, primary; S, secondary coil;
A, axis of lever; N. needle; Hg, mercury
cup.
In man, muscular fatigue can be studied by means of an arrange-
ment called an ergograph (Fig. 262). A record of successive con-
t-'ig. 259. — Fatigue Curve taken on a Slowly-moving Drum (reduced to Half): Frog's
Gastrccnemius. Excited through the sciatic nerve by maximal shocks once i«
six second*.
MECHANICAL PHENOMENA OF MUSCULAR CONTRACTION 751
•tractions, say, of one of the flexor muscles of a finger, in raising a
weight (isotonic method) or in deforming a spring (isometric method)
is taken on a drum. When the contractions are repeated every
second, or every half-second, distinct evidence of fatigue is seen on
the tracing after a longer or shorter
period, according to the conditions.*
What is the cause of muscular
fatigue ? An exact answer is not
possible in the present state of our
knowledge, but we may fairly con-
clude that in an isolated preparation
it is twofold : (i) Waste products,
among which some are so directly
related to the onset of fatigue as to
deserve the name of ' fatigue sub-
stances,' are formed by the active
muscle faster than they can be re-
moved, oxidized or otherwise decom-
posed. (2) The material necessary for
contraction is used up more quickly
than it can be reproduced or brought
to the place where it is required. That the accumulation of fatigue
products has something to do with the exhaustion is shown by the
fact that the muscles of a frog, exhausted in spite of the continuance
of the circulation, can be restored by bleeding the animal, or washing
out the vessels with physiological salt solution, while injection of a
watery extract of exhausted muscle into the bloodvessels of a
Fig. 260. — ' Staircase ' in Skeletal
Muscle : Frog. Stimulation by an
automatic arrangement.
Fig. 26?. — 'Staircase' in Cardiac Muscle. Contractions recorded on a much more
4iuilfely moving drum than in Fig. 260. The contractions were caused by stimu-
'lati^j a heart reduced to standstill by the first Stannius' ligature (p. 199). The
..contractions gradually increase in height.
curarized muscle renders it less excitable (Ranke). This observer
supposed that it was specially the removal of the acid products of
contraction which restored the muscle. Such acid products as
carbon dioxide and lactic acid, or the lactates which it may form
with bases in the blood, lymph or tissues, when they act on muscle
* Recent observations (by Ryan and Agnew) with improved methods have
emphasized the necessity for care in the interpretation of ergographic records.
This caution is timely, inasmuch as in modern war the question of the rela-
tion of fatigue to industrial practice acquires first-class importance.
752 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES
in more than a certain concentration, produce the same effects on
its power of contraction as are produced by fatigue, and there is
some reason to suppose that lactic acid is the most influential of the
fatigue substances. In smaller concentration, on the contrary, they
increase the excitability of the muscle, and, according to Lee, the
phenomenon of the ' staircase ' is due to the augmenting action of
these, and perhaps other fatigue substances, before they have accu-
mulated sufficiently to cause fatigue.
The lack of oxygen holds a conspicuous place among the con-
ditions which permit an excessive accumulation of fatigue substances,
and may contribute also to the failure of the processes normally
going on in the muscle which replenish the store of materials
needed for contraction. An isolated muscle is necessarily an
asphyxiated muscle, and the favourable action of an atmosphere
of oxygen on restoration of its contractile power after exhaustion
Fig. 262. — Ergograph (Mosso's, modified by Lombard).
(Fig. 123, p. 269) shows that asphyxia is itself an important*ilctor
in the onset of fatigue. Injection of arterial blood, or even of
an oxidizing agent like potassium permanganate, into the* vessels
of an exhausted muscle causes restoration (Kroneckeif. The
depletion of the available store of carbo-hydrate in the form of
glycogen (and dextrose) seems to be another factor in fatigue,
although not the chief direct cause of the phenomena associated
with that condition.
Seat of Exhaustion in Fatigue. — When a fatigued muscle responds
no longer to indirect stimulation, it can still be directly excited.
The seat of exhaustion must therefore be either the nerve-trunk
or the nerve-endings. It is not the nerve-trunk which is first
fatigued, for this still shows the negative variation (p. 824) on being
excited. And if the two sciatic nerves of a frog or rabbit be stimu-
MECHANICAL PHENOMENA OF MVSCULAk CONTRACTION 75$
lated continuously with interrupted currents of equal strength,
while the excitation is prevented from reaching the muscles of one
limb till those of the other cease to contract, it will be found that
when the ' block ' is removed the corresponding muscles contract
vigorously on stimulation of their nerve. The passage of a constant
current through a portion of the nerve or the application of ether
between the point of stimulation and the muscles may be used to
prevent the excitation from passing down (p. 813). Or a dose of
curara just sufficient to paralyze the motor inner vation may be
given to a rabbit, and the animal kept alive by artificial respiration.
The sciatic is now stimulated for many hours. As soon as the
influence of the curara begins to wear off, the muscles of the leg
contract.
The possible seats of fatigue caused by voluntary muscular con-
traction are (i) the muscle; (2) the nerve-endings (or the receptive
substances in the muscles, p. 739) ; (3) the nerve-trunk ; and (4) the
path of the voluntary motor impulses in the central nervous
system, which includes the pyramidal cells in the motor region of
the cerebral cortex (p. 875), the fibres of the pyramidal tract, and
the motor cells in the anterior horn of the spinal cord.
The two weak links in this chain appear to be the motor nerve- /•
endings and the muscles. The nerve-fibres, whether peripheral
or central, are certainly the strongest link. Ergographic experi-
ments have hitherto yielded results too discordant to justify any
very definite statement as to the point at which the chain snaps in
complete fatigue, if, indeed, it al vays necessarily breaks at the same
point. The muscles and motor en.iings appear to be always affected.
The position of the nerve centres, including the synapses (p. 852),
is in doubt. That the synapses easily lose their power of con-
ducting nerve impulses under the influence of repeated excitations
is indicated by the experiments of Sherrington on fatigue of reflex
mechanisms in which two or more afferent paths can cause discharge
along a common efferent path (p. 902). When excitation of one
of tke afferent paths has ceased to be effective, the reflex contrac-
tions can still be obtained on exciting the other. In this case the
molvor aieuron from cell-body to nerve-ending and the muscle are
eliminated as the seats of the fatigue block. Whether the tem-
porary loss of conduction in this case is comparable to the fatigue
of muscle, or is a perfectly different phenomenon (' pseudo-fatigue '
of Lee), scarcely bears on our present question. For if ' pseudo-
fatigue ' of afferent synapses can cause a reflex to miss fire, this at
least shows that the conductivity of the synapse is very easily affected
by repeated excitation, just as it is known to be very easily affected
by anaemia. The fact that a muscle, completely fatigued by direct
electrical stimulation, can still be voluntarily contracted, has been
supposed to indicate that the voluntary excitation is more effective
t54 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES
than any artificial stimulus. But the alternative explanation that
the electrical stimuli cannot be applied to a muscle in situ, so as to
cause uniform excitation, and therefore uniform fatigue, of all the
fibres of the muscle, is more probable (Hough).
It has been shown that the injection of the blood of an animal
exhausted by running or other muscular effort into the circulation
of a normal animal produces in the latter all the symptoms of fatigue.
Here the fatigue-producing substances will have the opportunity
of acting on both the central and the peripheral mechanisms. There
are reasons for believing that the fatigue process is fundamentally
the same in different tissues. The fatigue substances produced in
Fig. 253. — Influence of Mental Fatigue on Muscular Contraction, i, series of con-
tractions of flexors of middle finger before, and 2, series of contractions imme-
diately after, a period of three and a half hours' hard mental work. In both
cases the muscles were stimulated directly every two seconds by an electrical
current, and caused to raise a certain weight till temporary exhaustion occurred.
In the first series fifty-three contractions were found possible, in the second only
twelve (Maggiora).
muscle, and not immediately eliminated or transformed during
active muscular exertion, may therefore very well be a factor in
inducing fatigue of the central nervous mechanisms in addition to
the formation of fatigue products, and the using up of necessary
material in these mechanisms themselves. Conversely, active
and long-continued mental exertion may occasion muscular fatigue
(Fig. 263). The sensation of fatigue is alluded to in Chapter XVIII.
(d) The Influence of Drugs on the Contraction of Muscle. — The total
work which a muscle can perform, its excitability and the absolute
force of the contraction, may all be altered either in the plus or the
minus sense by drugs. But in connection with our present subject
those drugs which conspicuously alter the form and time-relations of
the muscle-curve have most interest. Of these veratrine is especially
MECHANICAL PHENOMENA OF MUSCULAR CONTRACTION 755
important. When a small quantity of this substance is injected below
the skin of a frog, spasms of the voluntary muscles, well marked in the
limbs, come on in a few minutes. These are attended with great
stiffness of movement, for while the animal can contract the extensor
muscles of its legs so as to make a spring, they relax very slowly, and
some time elapses before it can spring again. If it be killed before the
reflexes are completely gone, the peculiar alterations in the form of the
muscle-curve caused by veratrine will be most marked. The poisoned
1
wwwwwwww mw/mwm
Fig. 264. — Veratrine Curve compared with Normal: Frog's Gastrocnemius. The
tuning-fork marks hundredths of a second. Between i and 2 a portion of the
tracing corresponding to one and a half seconds has been cut out, and between
2 and 3 a portion corresponding to one second. The veratrine curve does not
show a peak. At 3 it has not yet fallen to the base-line.
muscle, stimulated directly or through its nerve, contracts as rapidly
as a normal muscle, while the height of the curve is about the same,
but the relaxation is enormously prolonged (Fig. 264). This effect
seems to be to a considerable degree dependent on temperature, and
it may temporarily disappear when the muscle is made to contract
several times without pause. Barium salts, and, in a less degree, those
of strontium and calcium, have an action on muscle similar to that of
veratrine. Sometimes the curve shows a peak (Fig. 265), due to a
rapid descent of the lever for a certain distance. This is followed by
a slow relaxation. The
peak appears to be analo-
gous to the initial con-
traction when a strong
voltaic current is passed
through a muscle, and
the rest of the curve to
the tonic contraction.
(e) The individuality of Fig 265.— Veratrine Curve: Frog's Gastrocnemius.
the muscle itself has an The curve shows a peak, the lever falling a littk
influence on the muscle- before the sustained contraction begins.
curve. Not only do the
muscles of different animals vary in the rapidity of contraction, but
there are also differences between the skeletal muscles of the same animal.
In the rabbit there are two kinds of striped muscle, the red and the
pale (the semitendinosus is a red, and the adductor magnus a pale
muscle), and the contraction of the former is markedly slower than
that of the latter. In many fishes and birds, and in some insects, a
similar difference of colour and structure is present.
Even where there is no distinct histological difference, there may be
great variations in the length of contraction. In the frog, for instance,
the hyoglossus muscle contracts much more slowly than the gastroc-
756 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES
nemius. The wave of contraction, which in frogs' striped muscle lasts
only about 0-07 second at any point, may last a second in- the forceps
muscle of the crayfish, though only half as long in the muscles of the tail.
In the muscles of the tortoise the contraction is also very slow. The
muscles of the arm of man contract more quickly than those of the leg.
Summation of Stimuli and Superposition of Contractions. — Hitherto
we have considered a single muscular contraction as arising from a
single stimulus, and we have assumed that the muscle has completed
its curve and come back to its original length before the next stimulus
was thrown in. We have now to inquire what happens when a second
stimulus acts upon the muscle during the contraction caused by a first
stimulus, or during the latent period before the contraction has actually
begun; and what happens when a whole series of rapidly-succeeding
stimuli are thrown into the muscle.
First let us take two stimuli separated by a smaller interval than
the latent period (p. 745). If they are both maximal — i.e., if each by
itself would produce the greatest amount of contraction of which the
muscle is capable when excited by a single stimulus — the second has
no effect whatever; the contraction is precisely the same as if it had
never acted. But if they are less
than maximal, the contraction,
although it is a single contraction,
is greater than would have been
due to the first stimulus alone; in
other words, the stimuli have been
summed or added to each other
during the latent period, so as to
produce a single result.
Next let us consider the case of
two stimuli separated by a greater
interval than the latent period, so
Fig. 266 -Superposition of Contractions. that the second falls lnto the
i is the curve when only one stimu us j during the contraction pro-
is thrown in; 2, when a second stimulus ,, 9- ™
. acts at the time when curve i has nearly duced by the first The result here
reached its maximum height. 1S verY different : traces of two con-
tractions appear upon the muscle-
curve, the second curve being that which the second stimulus would have
caused alone, but rising from the point which the first had reached at the
moment of the second shock (Fig. 266). Although the first curve is
cut short in this manner, the total height of the contraction is greater
than it would have been had only the first stimulus acted ; and this is
true even when both stimuli are maximal. Under favourable circum-
stances, when the second curve rises from the apex of the first, the total
height may be twice as great as that of the contraction which one
stimulus would have caused (p. 816). It is worthy of note that striated
muscle has no power of summation of subminimal stimuli each of which
is just too weak to cause contraction. No matter how rapidly they are
thrown in, the muscle remains at rest. It is otherwise with smooth
muscle. Stimuli which are singly ineffective cause contraction when
repeated.
Tetanus. — Not only may we have superposition or fusion of two
contractions, but of an indefinite number; and a series of rapidly
following stimuli causes complete tetanus of the muscle, which
remains contracted during the stimulation, or till it is exhausted
(Fig: 267).
MECHANICAL PHENOMENA OF MUSCULAR CONTRACTION 757
The meaning of a complete tetanus is readily grasped if, beginning
with a series of shocks of such rapidity that the muscle can just
completely relax in the intervals between successive stimuli, we
gradually increase the frequency (p. 816). As this is done, the
ripples on the curve become smaller and smaller, and at last fade
out altogether. The maximum height of the contraction is greater
than that produced by the strongest single stimulus ; and even after
complete fusion has been attained, a further increase of the fre-
quency of stimulation may cause the curve still to rise.
Fig. 267. — Analysis of Electrical Tetanus (reduced to f ). Four curves showing the
effect of increasing frequency of stimulation of the frog's gastrocnemius through
its nerve. In the lowest curve the frequency is such that the muscle relaxes
almost completely between the successive contractions. In the uppermost
curve, with a frequency more than three times greater, the contractions are
almost completely fused. In all the curves the fusion becomes more nearly
complete as stimulation goes on, owing to the slower relaxation of the fatigued
muscle.
It is evident from what has been said that the frequency of
stimulation necessary for complete tetanus will depend upon the
rapidity with which the muscle relaxes; and everything which
diminishes this rapidity will lessen the necessary frequency of
stimulation. A fatigued muscle may be tetanized by a smaller
number of stimuli per second than a fresh muscle, and a cooled by
a smaller number than a heated muscle. The striped muscles of
insects, which can contract a million^ times in an hour, require
300 stimuli per second for complete tetanus, those of birds 100,
of man 40, the torpid muscles of the tortoise only 3. The pale
muscles of the rabbit need 20 to 40 excitations a second, the red
758 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES
muscles only 10 to 20; the tail muscles of the crayfish 40, but the
muscles of the claw only 6 in winter and 20 in summer. The
gastrocnemius of the frog requires 30 stimuli a second, the hyo-
glossus muscle only half that number (Richet). The frequency of
stimulation necessary for complete tetanus of unstriped muscle
is much less than for striped muscle. Smooth tetanus of a band of
muscle from the frog's stomach was obtained with strong opening
induction shocks at the rate of i in 5 seconds.
There appears also to be an upper limit beyond which a series of
stimuli becomes too rapid to produce complete tetanus, and at which an
interrupted current acts like a constant current, causing a single twitch
at its commencement or at its end, but no contraction during its pas-
sage. This limit does not depend upon the frequency of stimulation
alone; the intensity of the individual excitations, the temperature of
the muscle, and probably other factors, affect it. For Bernstein found
that with moderate strength of stimulus tetanus failed at about 250
per second, and was replaced by an initial contraction; with strong
stimuli at more than 1,700 per second, tetanus could still be obtained.
Kronecker and Stirling saw tetanus even with 4,000 shocks a second.
Kries in a cooled muscle found tetanus replaced by the simple initial
twitch at 100 stimuli per second, although in a muscle at 38° C. stimu-
lation of ten times this frequency still caused tetanus. Einthoven,
exciting the nerve of a frog's nerve-muscle preparation with extremely
frequent oscillatory condenser discharges, observed tetanus up to even
a million vibrations a second, if the current intensity was at the same
time very greatly increased (to more than 16,000 times the intensity
needed with a constant current). These results are not really so dis-
cordant as they appear ; for it is known that with electrical stimulation
the number of excitations is not necessarily the same as the nominal
number of shocks. By applying a telephone to a muscle excited through
its motor nerve, it has been shown that the pitch of the note produced
by the tetanized muscle corresponds exactly to the rate of excitation
up to a certain frequency. This frequency is about 200 per second for
frog's and about 1,000 per second for mammalian muscle under the
best conditions. If the rate of excitation is still further increased, there
is no corresponding increase in the pitch. Therefore, some of the
stimuli are now producing no effect — ' falling flat,' so to speak (Weden-
sky). A physical reason for this is the overlapping of the make and
break shocks (Erlanger and Garrey) ; and a physiological reason, the
alterations of conductivity and excitability, which even very brief
currents leave behind them (Sewall), and which we shall have to discuss
in another chapter.
It is only while the actual shortening is taking place that a tetanized
muscle can do external work. But, although during the maintenance
of the contraction no work is done, energy is nevertheless being ex-
pended for the metabolism of a muscle during tetanus is greater than
during rest, and, among other changes, lactic acid is produced. There
are great differences in the ease with which different muscles can be
exhausted by tetanus. For example, the muscles which close the
forceps of the crayfish or lobster have, as everyone knows, the power
of most obstinate contraction. Richet tetanized one for over seventy
minutes, and another for an hour and a half, before exhaustion came
on, while a tetanus of a single minute exhausted the muscles of tLe
crayfish's tail. The gastrocnemius of a summer frog kept up for twelve
minutes, and a tortoise muscle for forty minutes.
Continuous stimulation is not always necessary for the production
of continuous contraction; in some conditions a single stimulus is suffi-
cient. A blow with a hard instrument may cause a dying or exhausted,
and in thin persons even a fairly normal, muscle to pass into long-
continued contraction. This so-called ' idio-muscular ' contraction
seems to depend, in part at least, on the great intensity of the stimulus.
It can sometimes be obtained in the frog's gastrocnemius, particularly
in spring after the winter fast. It is not a tetanus and is not propa-
gated along the muscular fibres, as an electrical tetanus is, but remains
localized at the spot where it arises. Similar non-tetanic contractions
have already been mentioned, such as the tonic contraction during the
passage of a strong voltaic current and the sustained veratrine contrac-
tion. Ammonia causes also a long but non-tetanic contraction, and this,
too, does not spread when the substance has acted only on a portion
of the muscle. The contraction force of all these tonic contractions,
as measured by the resistance necessary to overcome or prevent them,
is less than the contraction force in electrical tetanus (Schenck).
The rate at which the wave of muscular contraction travels may be
measured by stimulating the muscle at one end, and recording, by
means of levers, the movements of two points of its surface as far
apart from each other as possible. Time is marked on the tracing by
means of a tuning-fork, and the distance between the points at which
the two curves begin to rise from the base-line divided by the time gives '
the velocity of the wave. Another method is founded upon the measure-
ment of the rate at which the negative variation (p, 824) passes over
the muscle, this being the same as the velocity of the contraction-wave.
In frog's muscle it is about three metres a second, or six miles an hour.
Rise of temperature increases, fall of temperature lessens it. When a
muscle is excited through its nerve, the contraction springs up first of
all about the middle of each muscular fibre where the nerve-fibre enters
it, and then sweeps out in both directions towards the ends. But so
long is the wave, that all parts of the fibre are at the same time involved
in some phase or other of the contraction.
The wave of contraction in unstriped muscle lasts a relatively long
time at any given point, and in tubes like the intestines and ureters,
the walls of which are largely composed of smooth muscle arranged in
rings, the wave shows itself as a gradually-advancing constriction
travelling from end to end of the organ. There is no evidence that
the contraction of smooth muscular fibres is discontinuous — that is,
:omposed of summated contractions like a tetanus ; it appears to be a
greatly-prolonged simple contraction. An artificial stimulus, mechani-
cal or electrical, causes, after a long latent period, a very definitely-
localized contraction in a rabbit's ureter, which slowly spreads in a
peristaltic wave in one or both directions along the muscular tube.
Here, as in the cardiac muscle, the excitation passes from fibre to fibre,
while in striped skeletal muscle only the fibres excited directly or
through their nerves contract. That the rhythmical contraction of
the heart is not a tetanus has already been seen. It is a simple con-
traction, intermediate in its duration and other characters between the
twitch of voluntary muscle and the contraction of smooth muscle. The
contraction both of unstriped and of cardiac muscle is lengthened and
made stronger by distension of the viscera in whose walls they occur,
just as a skeletal muscle contracts more powerfully against resistance.
760 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES
Voluntary Contraction. — There is evidence that the voluntary
contraction is a tetanus. One of the strongest buttresses of the
theory of natural tetanus has been the muscle-sound, a low rumbling
note which can be heard by listening with a stethoscope over the
contracting biceps, or, when all is still, by stopping the ears with the
fingers and strongly contracting the masseter and the other muscles
concerned in closing the jaws.* Discovered about ninety years
ago, first by Wollaston and then by Erman, half a century passed
away before it was investigated more fully by Helmholtz. The
latter observer, confirming the results of his predecessors, put down
the pitch of the sound at 36 to 40 vibrations per second. He found,
however, that little vibrating reeds with a rate of oscillation of about
19-5 per second were more affected when attached to muscle thrown
into voluntary contraction, than those that vibrated at a smaller
or a greater rate. He therefore concluded that the fundamental
tone of the muscle corresponded to this frequency, although, since
such a low note is not easily appreciated, the sound actually heard
was really its octave or first harmonic (p. 310).
The objection has been brought forward that the resonance tone of
the ear also corresponds to a vibration frequency of 36 to 40 a second.
In other words, this is the natural rate of swing of the elastic struc-
tures in the middle ear, the rate they will most easily fall into if set
moving by an irregular mixture of faint, low-pitched tones and noises,
and not compelled to vibrate at some other rate by a distinct sound
of definite pitch. Now, this resonance tone might be elicited by a
quivering muscle if, among many diverse rates of oscillation of different
portions of its substance, the rate of 36 to 40 a second anywhere ap-
peared, and the note corresponding to the real rate of vibration of the
muscle as a whole might be overpowered. Or, even if there were no
regular rate of vibration of the whole muscle, but, instead, a series of
irregular tremors or pulls due to irregularities in the contraction, con-
nected with a want of co-ordination of all the fibres (Haycraft), the ear
might from time to time pick out of the turmoil of feeble aerial waves
those corresponding to its resonance tone, just as a tuning-fork or a
piano-string attuned to a particular note would catch it up amid a
thousand other sounds and strengthen it.
But while this renders it highly probable that the resonance of the
ear contributes to the production of the muscle-sound, and shows that
we cannot from the pitch of the muscle-sound alone deduce the rate
at which the muscle-substance is vibrating, it does not invalidate
Helmholtz's objective observations with the oscillating reeds.
And several observers (Schafer, Horsley, v. Kries) have noticed
periodic oscillations, at the rate of 10 or 12 per second, in the
curves taken from muscles (Fig. 268), contracted voluntarily
against a small resistance. When the resistance is greater, the
rate may be as much as 18 or 20 a second, and in quick and rapidly
* In order that a muscular sound may be produced there must be a certain
abruptness in the contraction. Thus, the slowly-contracting smooth muscles
do not produce a sound, nor the slowly-contracting heart-muscle of cold-
blooded animals.
MECHANICAL PHENOMENA OF MUSCULAR CONTRACTION 761
repeated movements of the fingers even 40 a second. In habitual
movements, such as those employed by a man in his trade, the
tremors are much less coarse than in unaccustomed movements.
For this reason the tremors of the left hand are greater than those
of the right in executing a movement usually made with the latter
(Eshner). In disease these tremors are often increased — e.g., in
the clonic convulsions of epilepsy — tout the frequency is the same.
Fig. 268. — Vibrations of Contracted Arm Muscles (Griffiths). The arm was stretched
out, holding a weight of about 6 kilos.
Similar vibrations, and at about the same rate, are seen in curves
traced by muscles excited through stimulation of the motor areas
of the surface of the brain. Since this rate remains the same whether
the motor cortex, the corona radiata, or the spinal cord is excited,
and, unlike the rate of response to excitation of peripheral nerves,
is independent of the frequency of stimulation (so long as the rate
of stimulation is greater than 10 or 12 a second), it has been supposed
to represent the /
rhythm with which
impulses are dis-
charged from the
motor cells of the cord
(Fig. 269). It is prob-
able that the cortical
centres discharge at
about the same rate,
for not only is it im-
possible to articulate
more rapidly than
eleven syllables per
second, but it is impossible to reproduce the act of articulation in
thought at a greater rate than this (Richet). But while this rate
of 10 or 12 a second does seem to represent a fundamental rhythm
of the central discharge, there are facts which indicate that upon
this relatively slow rhythm a quicker rhythm is superposed. In
other words, each of these discharges is itself discontinuous, and
made up of a number of separate impulses.
Fig. 269.-
-Contractions caused by Stimulation of the
Spinal Cord.
762 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES
Thus, according to Piper, the total number of simple discharges,
each associated with an electrical change in the muscle, as recorded by
the string galvanometer, is 47 to 50 a second. The rhythm of strych-
nine tetanus in the frog is about 8 to 12 per second. By means of the
capillary electrometer (p. 729) large electrical oscillations at this rate
can be demonstrated, each of which represents a short tetanic spasm,
as is shown by the fact that a number of smaller electrical oscillations
are superposed upon the large ones (Sanderson). The electrical changes
suggest that each discharge causes a simple contraction much more
prolonged than the twitch of a directly stimulated muscle. This
removes the difficulty of understanding how such a small number as
10 contractions per second could be smoothly fused, and indicates that
even the shortest possible voluntary movement, which can be executed
in i"& to -£$ of a second, is not caused by a single impulse, but is a
tetanus. For these brief movements the frequency of oscillation, as
shown by the action currents, is the same as for sustained contractions.
The electrical changes in the voluntarily contracted muscle seem to
differ in amplitude or abruptness from those produced in experimental
tetanus. For secondary tetanus (p. 833) is not caused by muscle in
voluntary contraction. But this is also the case with the other pro-
longed contractions caused by continuous artificial stimulation — e.g.,
Ritter's tetanus (p. 741) and the contraction produced by sodium
chloride or ammonia. We need not hesitate to conclude, then, that
the voluntary contraction is discontinuous, in the sense that it is not
a perfectly smooth and uniform tonic contraction, although we still
lack a decisive proof that it is maintained by a strictly intermittent
outflow of nervous energy, and not by a continuous outflow causing a
sustained contraction, which, it may be, remits and is reinforced at
intervals. The apparent discrepancies as to the rate of discharge in
the results obtained by different observers, and by different methods,
far from exciting distrust of them all, really lend support to the idea
of a fundamental and fairly constant rhythm in the outflow as soon
as it is recognized that the higher rates are approximately multiples
of the lower. Thus, the number deduced by Helmholtz from the ex-
periment of the springs is twice the lowest rate calculated from graphic
records of the contraction. The rates corresponding to the muscle-
sound and to the frequency of the electrical oscillations are about four
times this number. Now, in a vibrating elastic body like a contracting
muscle, a simple mathematical relation of this sort might be expected
to appear when determinations of the rate of oscillation and of accom-
panying periodic changes are made by methods varying in principle and
in delicacy. For instance, an arrangement suited to record and to
count coarse vibrations could not be expected to give the same result
as an arrangement suited to record and count fine vibrations. But if
both the coarse and the fine vibrations were related to a fundamental
rhythm, a simple proportion might be expected to exist between the
two sets of results.
(3) Thermal Phenomena and Transformation of Energy in the
Muscular Contraction. — When a muscle contracts, its temperature
rises ; the production of heat ,jn it is increased. This is most dis-
tinct when the muscle is tetanized, but has also been proved for
single contractions. The change of temperature can be detected
by a delicate mercury or air thermometer; and, indeed, a ther-
mometer thrust among the thigh-muscles of a dog may rise as much
THERMAL PHENOMENA OF MUSCULAR CONTRACTION 763
as i° to 2° C. when the muscles are thrown into tetanus. In the
isolated muscles of cold-blooded animals the increase of tempera-
ture is much less ; and thermo-electrical methods, which are the
most delicate at present known, have generally been used for its
detection and measurement.
They depend upon the fundamental fact of thermo-electricity, that
in a circuit composed of two metals a current is set up if the junctions
of the metals are at different tempera-
tures.
Where no very fine differences of
temperature are to be measured, a single
thermo-j unction of German silver and
iron, or copper and iron, is inserted into
a muscle or between two muscles. But
the electromotive force, and therefore
the strength of the thermo-electric cur-
rent, is proportional for any given pair
of metals to the number of junctions,
and for delicate measurements it may
be necessary to use several connected
together in series. A thermopile of
antimony - bismuth junctions gives a
stronger current for a given difference of
temperature than the same number of
German silver-iron couples, but from its
brittle nature is otherwise less convenient .
The direction of the current in the cir-
cuit is such that it passes through the
heated junction from bismuth to anti-
mony and from copper or German silver
to iron. Knowing this direction, we are
aware of the changes of temperature
which take place from the movements
of the mirror of the galvanometer with
which the pile is connected. In the
thermopiles employed in the recent ex-
tensive investigations of Hill the alloy
constantan is coupled with iron, the
electromotive force of this combination
being exceptionally great.
The muscle which is to be excited is
brought into close contact with one
junction or set of junctions, the other
set being kept at constant temperature.
The image will now come to rest on the
scale; and excitation of the muscle will
cause a movement indicating an increase
of temperature in it, the amount of which
can be calculated from the deflection. In
one form (Fig. 270) the thermopile con-
stitutes a hollow cone, in which a muscle can be arranged so as to eliminate
largely the errors due to differences of temperature of the muscle, or to
the " slip " of the contracting muscle over the junctions.
In this way Helmholtz observed a rise of temperature of 0-14° to
o -18° C. in excised frogs' muscles when tetanized for a couple of minutes .
S
Fig. 270. — Conical Thermopile
containing Gastrocnemius Mus-
cle Reversed. C, copper leads
to galvanometer; S, stimulating
wire. The straight lines indicate
iron, the crossed lines constan-
tan, the external junctions em-
bedded in the ebonite frame
being at a, the internal junc-
tions, b, in contact with the
muscle.
764 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES
Heidenhain, with a very delicate pile, found a rise of 0-001° to
0-005° C. for a single contraction of a frog's muscle. On the assump-
tion that the pile had time to take on the temperature of the
muscle before there was any appreciable loss of heat, this would
be equal to the production by every gramme of muscle of a thou-
sandth to five-thousandths of a gramme-calorie (p. 676) of heat.
From pick's observations we may take about three-thousandths
of a gramme-calorie as the maximum production of a gramme of
frog's muscle in a single contraction.
Hill has shown that in the case of the single contraction or twitch
the evolution of heat may be so rapid as to be practically instan-
taneous, indicating that it depends upon some sudden ' explosive '
chemical reaction; or, on the other hand, under certain conditions
it may last as long as two
seconds — that is, from four
to ten times as long as the
contraction itself. In the
absence of oxygen, when
the muscle is left, for in-
stance, in an atmosphere of
hydrogen, the heat produc-
tion becomes markedly pro-
longed. When abundant
oxygen is supplied, the dura-
tion of the discharge of heat
is decreased. In a tetanus
the evolution of heat lags
behind the excitation, and
the discharge associated
with each stimulus is not
complete till 0-5 to 2-5
seconds after the stimulus. In a prolonged complete tetanus
the heat production corresponding to the first tenth of a second
of excitation is far greater than that corresponding to the second
tenth of a second, and so on, until eventually a uniform dis-
charge of heat, at a rate much smaller than the initial rate, is
reached. When frogs' muscles are rapidly stimulated indirectly
(through the nerves) till fatigue has occurred, the maximum value
of the heat evolved approximates to 0-9 gramme - calorie per
gramme of muscle, about 70 or 80 per cent, being liberated in the
first two minutes (Peters).
A fact of great significance in regard to the relation of the reaction
upon which the heat production depends and the mechanical
conditions in the acti^ muscle is that the production of heat is
determined by the length of muscular fibres existing at the time
when the heat is being evolved. From this it has been assumed
that the production of heat in active muscle is a surface effect, and
Fig. 271. — A, a single copper-iron thermo-
electric couple ; B,two pairs, one inserted into
the tissue b, the other dipping into water in a
beaker a. The temperature of the water
may be adjusted so that the galvanometer
shows no deflection. The temperature of the
tissue is then the same as that of the water.
THERMAL PHENOMENA OF MUSCULAR CONTRACTION 765
not an effect taking place uniformly throughout the muscle substance
and related accordingly to the volume or mass of the muscular
substance (Blix). Much evidence has been accumulated in favour
of this hypothesis. For example, a muscle contracting isometrically
(p. 747) produces more heat the greater is the initial tension (the
more it is stretched at the begining of the excitation) — 'that is,
the greater its length during contraction (Heidenhain). When a
muscle is allowed to shorten in a tetanus, the heat production as
compared with that of an isometric contraction of the same dura-
tion, and evoked by the same strength of stimulus, is diminished
by as much as 40 per cent.
Relation between the Development of Mechanical Energy and
Heat Production in Active Muscle. — There is no simple relation
between the external work done in a muscle twitch and the heat
set free. The efficiency of the muscular machine, as estimated
by the proportion of the work done to the total energy degraded,
varies with a number of factors — e.g., the load, the number of fibres
excited, and the intensity of the excitation of each fibre, the two
lattjer factors depending upon the strength of the stimulus.
The greater the resistance, so long as the muscle can overcome
it so as to do its utmost amount of external work,* the larger is
the proportion of energy which appears as work, the smaller the
proportion which appears as heat. For every muscle, under given
conditions, there is a certain load which can be raised more advan-
tageously than any other; but even in the most favourable case,
an excised frog's muscle never does work equal to more than £ of
the heat given off. Generally the ratio is much less, and may sink
as low as -£g. In the intact mammalian body the muscles work
somewhat more economically than the excised frog's muscles at
their best; for both experiment and calculation show (p. 687)
that in a normal man under the most favourable conditions as
much as 1 of the energy is converted into work. According to
Zuntz and Katzenstein, 35 per cent, of the total energy appeared
as muscular work in climbing a mountain, and in bicycling only
25 per cent. Movements which have been much practised are
more economically performed than unaccustomed ones, and this
explains the superior efficiency of the muscles concerned in climbing,
for no movements can possibly be more familiar than those con-
cerned in locomotion. So far as this indication goes, it would seem
that in the treatment of obesity unfamiliar, and therefore physio-
logically expensive, forms of exercise should be recommended, in
so far, of course, as they do not injuriously react upon the general
condition, especially upon the circulation.'
* This statement, based on experiments with excised frog's muscles, is not,
of course, inconsistent with the fact mentioned on p. 687, that in the intact
body the fraction of the energy transformed into heat is greater in hard than
in moderate work.
766 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES
When a muscle, excited by maximal stimuli, is made to lift con-
tinuously increasing weights, both the work done and the heat given
out increase up to a certain limit. The muscle, as it were, burns the
candle at both ends. The heat-production reaches its maximum some-
what sooner than the work.
It is certain that when work is done by a muscle an equivalent
amount is subtracted from its sum-total of energy, and under proper
conditions this can be actually demonstrated by the deficiency in the
heat-production. This is done by means of a contrivance called a
work-adder. It consists of a wheel, the rotation of which raises a
weight attached to a cord wound round its axle. The muscle acts on
the periphery of the wheel, and by rotating it raises the weight a little
at each contraction. At the end of the contraction the wheel is pre-
vented from moving back by a catch. The work done in a series of
contractions is calculated from the total height to which the weight
has been raised. Suppose a frog's gastrocnemius is made to contract
a certain number of times while attached to the work-adder, and that
simultaneously the heat- production is measured by means of a thermo-
pile. Let H represent the heat actually produced, and h the heat
equivalent of the work done. Now let the muscle be disconnected from
the adder and made to raise the same weight, directly attached to it,
by a series of contractions elicited in precisely the same way as the
previous ones, except that the weight is allowed to fall with the muscle
when it relaxes after each contraction. Here heat corresponding to the
external work disappears from the muscle during the contraction just
as in the first experiment, but this heat is returned to the muscle during
the relaxation, since on the whole no external work is done. The heat
produced in the second experiment is found, as a matter of fact,
allowing for unavoidable errors, to be equal to H'+h.
According to Hill, the true ' efficiency ' of the muscle is not the
ratio W/H, where W is the external work and H the total heat liberated,
but T/H where T is the maximum increase of tension set up during the
twitch when the muscle is contracting isometrically. This fraction T/H
is constant whatever be the initial tension, the number of fibres excited,
or the strength of excitation of each fibre. For the theory of the
muscular contraction the tension auring an isometric muscle twitch,
which represents the potential energy suddenly developed in conse-
quence of the excitation, is accordingly much more important than the
height of the contraction, which is related to the work actually done.
The essential thing in muscular contraction may be the abrupt develop-
ment of this tension through a chemical reaction which liberates certain
substances at some membrane or surface in the muscle. The potential
energy once in being may or may not be transformed into work, and if
so transformed the change may be accomplished economically or waste-
fully, according to the conditions of the contraction. The ratio T/H
decreases in fatigue, and with the time during which the muscle has
been deprived £fi its blood-supply. Hill has calculated the absolute
value of the hfcat-production in tetanus of a sartorius or semimem-
branosus muscle of the frog. This quantity, reckoned per centimetre
of length of the muscle, per gramme weight of the tension developed
and per second of maintenance of the tension, is relatively constant at
about 0-000015 'gramme-calorie. Including the recovery processes of
oxidation following the contraction the total heat-production would
amount to about 0-000025 calorie. The potential energy possessed by
a muscle of a length of a centimetre when maintaining a tension of a
gramme is abowt 0-000004 calorie. So that to maintain this state of
potential energy six or seven times as much energy must be liberated
CHEMICAL PHENOMENA OF MUSCULAR CONTRACTION 767
per second. The maintenance of prolonged tension is, therefore, from
the point of view of the mechanical result, an exceedingly wasteful
process, with a very low efficiency in comparison with the high efficiency
in a rapid twitch. This enables us to see how important a part in heat-
production, and therefore in temperature regulation, the tonusof muscle
and the prolonged contractions of shivering may possess (p. 695).
We are as yet in the dark as to the precise relation of the energy
which appears as heat and of that which is converted into work.
The ultimate source of both is, of course, the oxidation (and
cleavage) of the food substances. It was at one time a favourite
theory that in a muscle, as in a heat-engine, the chemical energy
is first converted into heat, and part of the heat then transformed
into work. There is no evidence that this is the case. It is,
indeed, impossible that such differences of temperature can exist
as would be compatible with the known efficiency of the muscular
machine. Hypotheses based on the assumption that the chemical
energy is immediately changed into work, perhaps through the pro-
duction of surface effects, have met with increasing favour, but
data are as yet too few for the formulation of any really satisfactory
theory. The close relation between the heat-production and the
formation of lactic acid in contraction which have been shown to
exist, is a suggestive fact whose full significance will only be revealed
by further investigation. The restitution processes by which the
original state of the muscle is restored after contraction are, of
course, intimately related to those concerned in the actual shorten-
ing ; but unless we know how, and in consequence of what chemical
or physical changes, the equilibrium of the resting muscle has been
disturbed, we cannot know how, or in consequence of what chemical
or physical changes, it is restored.
SECTION IV. — CHEMICAL PHENOMENA OF THE MUSCULAR
CONTRACTION.
The composition of dead mammalian muscle of the striped variety may
be stated, in round numbers, as follows, but there are considerable
variations, even within the same species:
Water - 75 per cent.
Proteins - - 20 ,,
Fats, lecithin, and cholesterin - - 2 „
Nitrogenous extractives, creatin (about 0-4 peri
cent.), carnosin, phospho-carnic acid, inosinic
acid, purin bodies, such as uric^cid, hypoxan-
thin, xanthin, etc. -
Carbo-hydrates (glycogen, dextrose, maltose)
Non-nitrogenous organic substances (lactic acid,
inosit)
Pigment (myohaematin or myochrome, a haemoglobin not precisely
identical with that of blood).
Inorganic substances less than i per cent, (chlorides, carbonates,
phosphates, and sulphates of potassium, sodium, iron, calcium,
magnesium) . Potassium is absent from the nuclei (Frontispiece).
758 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES
Of the nitrogenous extractives, creatin (p. 597) and carnosin are
present in greatest quantity, muscle containing 0-2 to 0-4 per cent, of
kreatin. Carnosin (CgHj^^C^) is a substance with basic properties,
and can be split up into histidin and /3-amino-propionic acid, an
amino-acid not identical with alanin (or a-amlno-propionic acid), but
having the NH2 coupled to the tf instead of the a carbon atom (p. 566^.
There is more water in the muscles of young than of old animals
(v. Bibra), and more in tetanized than in rested muscle (Ranke). The
fats are variable in amount, and belong to a small extent to the actual
muscle-fibres. For even when the visible fat is separated with the
utmost care, nearly i per cent, of fat still remains (Steil).
The glycogen content varies extremely in different muscles and in
the same muscle under different nutritive and functional conditions.
Thus, in one and the same dog the biceps brachii contained 0-17 and
the quadriceps femoris 0-53 per cent. In dogs on a diet rich in carbo-
hydrate and protein the percentage in the whole skeletal musculature
ranged from 0-7 to 3-7, and in the heart from o-i to 1-2. The average
for human muscles has been given as 0-4 per cent. In lean horse-flesh
Pfliiger found 0-35 per cent, of glycogen, but no sugar. The total
nitrogen was 3-21 per cent, of the moist tissue. The lactic acid of
muscle and other tissues is the d- lactic acid , which rotates the plane of
polarization to the right. By the action of certain bacteria on cane-
sugar /-lactic acid is obtained, which is left rotatory. The optically
inactive fermentation lactic acid is obtained by the fermentation of
lactose.
Smooth muscle is somewhat richer in water than the striated variety
from the same species, because skeletal muscle is richer in fat. Glycogen
is either absent or present only in traces in the smooth muscle (of the
stomach and bladder). Lactic acid, creatin, and creatinin are also
found in much smaller amount than in striped muscle (Mendel and Saiki) .
As in striated muscle, hypoxanthin is the conspicuous purin base
occurring in the free form — i.e., obtainable in muscle extracts. The
most remarkable difference in the quantitative relations of the inorganic
constituents is that in striated muscle potassium preponderates over
sodium and magnesium over calcium, whereas in the smooth variety
this relation is reversed.
It would be natural to expect that the proteins, which bulk so
largely among the solids of the dead muscle, and which are so obvi-
ously important in the living muscle, should be affected by contrac-
tion. But up to the present time no quantitative difference in the
proteins of resting and exhausted muscle has ever been made out.
The quantity of creatin (and creatinin) is said by some authorities
to be increased. The following chemical changes have been defi-
nitely established. In an active muscle —
(a) More carbon dioxide is produced, (b) More oxygen is consumed.
(c) Lactic acid is formed, (d) Qfc^>gen is used up. (e) The substances
soluble in water diminish in ai^^Ht; those soluble in alcohol increase.
Production of Carbon Dioxide and Consumption of Oxygen during
Contraction. — This subject has already been dealt with in part in
connection with tissue respiration (p. 266). The fact that muscular
exercise increases the carbon dioxide output and the oxygen absorp-
tion at the pulmonary surface, shows that oxidation processes
involving ultimately the combustion of carbon-containing substances
CHEMICAL PHENOMENA OF MUSCULAR CONTRACTION 7&>
are associated with the activity of the muscular tissue, but does
not of itself prove that the final steps of the oxidation occur in the
muscles themselves. This has been demonstrated, however, by
observations on isolated muscles. When well supplied with
oxygen, these, in addition to the stock of carbon dioxide in solution,
in the form of carbonates and in other combinations, which they
possess at the moment of isolation, continue to produce carbon
dioxide, and this production is markedly increased by stimulation.
The best evidence is to the effect that only preformed carbon dioxide
is given off by isolated muscles in the absence of oxygen. They
can go on contracting indeed, as previously stated, in an atmosphere
of hydrogen or nitrogen, and may seem to be producing carbon
dioxide, but the increased output appears to be due simply to an
accelerated decomposition of already existing carbonates, or perhaps
other combinations in which carbonic acid is loosely held, brought
about by lactic acid, which in the absence of oxygen, is not trans-
formed as it is under normal conditions, and accumulates in the
muscular substance, uniting with bases, and thus displacing
carbonic acid.
Formation of Lactic Acid — Reaction of Muscle. — To litmus-paper
fresh muscle is amphicroic — that is, it turns red litmus blue and blue
litmus red. This is due, partly at least, to the phosphates. Mono-
phosphate (tribasic phosphoric acid, H3PO4, in which one hydrogen
atom is replaced, say, by sodium or potassium) reddens blue litmus,
while diphosphate (where two hydrogen atoms are replaced) turns red
litmus blue. Litmoid (lacmoid) differs from litmus in not being affected
by monophosphates. Diphosphates turn red litmoid blue, and so does
fresh muscle, which has no effect on blue litmoid. A cross-section
of fresh muscle is about neutral (sometimes faintly acid) to turmeric
paper, which is turned yellow by monophosphates. A muscle which
has entered into rigor or has been fat \gued by prolonged stimulation is
distinctly acid to blue litmus and to brown turmeric, reddening the
former and turning the latter yellow, but does not affect blue litmoid.
Perfectly fresh resting muscle excised with avoidance of all un-
necessary manipulation contains very little lactic acid (as little as
0-02 per cent, expressed as zinc lactate). Mechanical injury,
heating, and chemical irritation cause a marked increase in the
amount. Under anaerobic conditions — in an atmosphere of
hydrogen, for instance — lactic acid is spontaneously developed in
the resting muscle so long as irritability persists, but not longer.
In air, which for even^mall excised muscles corresponds to a partial
asphyxia, there is a small increase in the lactic acid, but its pro-
duction is very slow in comparison with that in the hydrogen
atmosphere. In pure oxygen not only is there no accumulation
of lactic acid for a long time after excision, but a portion of the
amount originally present in the resting excised muscle disappears.
The same is true of the lactic acid formed in a muscle fatigued by
stimulation when it is afterwards placed in an atmosphere of pure
49
770 THE PHYSIOLOGY OP THE CONTRACTILE TISSUES
oxygen. There is no doubt that the production of lactic acid in
functional activity and its transformation into other substances
are processes that go on also in the muscles of the intact body.
The formation of the acid in the excised muscle, far from being a
sign of death, is an index of the ' survival ' of a process by which
it is normally formed, as the accumulation of it is an index of the
crippling, in the absence of oxygen, of a mechanism by which it is
normally transformed.
The lactic acid which accumulates in the excised muscle in rigor
and activity does not remain free, since blue litmoid paper is not
reddened as it would be by free lactic acid. It causes a repartition
of the bases at the expense of the sodium carbonate and disodium
phosphate, the latter being changed into monophosphate, which,
in part at least, accounts for the acid reaction to turmeric (Roh-
mann). It is of great interest that this oxi dative transformation
of lactic acid only occurs in muscle whose structure is so far pre-
served that its irritability is not lost. In minced or triturated
muscle it does not take place.
The relations between the heat production, the formation of
carbon dioxide, and the production of lactic acid indicate that
liberation of lactic acid from some precursor is an essential stage
in the sudden, ' explosive ' reaction or series of reactions which
precedes and induces the mechanical response to stimulation. This
stage takes place whether oxygen be present or absent, and it seems
to be accompanied by a considerable liberation of energy, at the
expense of which alone the anaerobically contracting muscle works.
It is most probable that the liberation of lactic acid follows the same
course in the muscle abundantly supplied with oxygen, although it
has not been shown that oxidative processes, resulting in the forma-
tion of carbon dioxide, do not contribute also at this stage to the
energy which is transformed into the mechanical effect. But while
in the absence of oxygen the reaction stops at the formation of
lactic acid, when oxygen is available the cycle is completed by
restitution processes which lead to the disappearance of the lactic
acid either by restoration to its original position in the precursor
from which it is derived, or perhaps in the case of a portion of the
tactic acid to its combustion to carbon dioxide and water. For
these restitution processes oxygen is essential, and it is to be
supposed that the energy required for the rebuilding of the lactic
acid precursor, or, to speak more generally, for the restoration of
the muscle to its original state in readiness for a fresh contraction,
is derived largely from oxidations in which carbon dioxide makes
its appearance.
The Precursor of Lactic Acid. — What material is the lactic acid
formed from ? There are reasons for thinking that lactic acid is an
intermediate substance which in metabolism serves as a link between
CHEMICAL PHENOMENA OF MUSCULAR CONTRACTION 771
the products of protein decomposition and carbo-hydrates, and
between carbo-hydrates and fat. From what we know of the
production of lactic acid both outside the body and in the intestine
from carbo-hydrates, it might seem a most plausible suggestion
that in the active muscle it comes from glycogen.
Glycogen is the one solid constituent of muscle which has been
definitely proved to diminish during activity. It accumulates in
a resting muscle, especially in a muscle whose motor nerve has been
cut; but rapidly disappears from the muscles of an animal made
to do work while food is withheld; or from the muscles of an animal
poisoned by strychnine.which causes violent muscular contractions.
But the best evidence points the other way — e.g., in rigor mortis
lactic acid is produced just as in muscular contraction. Nay,
more, the amount of lactic acid (as much as 0-5 per cent, expressed
as zinc lactate) produced in full heat rigor (at 40° to 45° C.) is con-
stant for similar excised muscles. This ' acid-maximum ' is the
same when fresh muscle is at once put into rigor; or when fatigue
is first induced, with formation of lactic acid, before rigor; or,
finally, when the lactic acid of the fatigued muscle is caused to
disappear under the influence of oxygen, and heat rigor is then
brought about in the muscle (Fletcher and Hopkins). Yet in rigor
mortis the quantity of glycogen is unaltered (Boehm). Further,
under certain conditions an excised muscle is capable of producing
a quantity of lactic acid much greater than could be derived from
the glycogen contained in it.
An indirect argument against the view that the lactic acid pre-
cursor is glycogen has been based by Hill on the results of his studies
on the heat production of surviving muscle. From the amount
of heat evolved, he calculates that the precursor of lactic acid
must have a heat value 10 per cent, greater than that of lactic acid.
Now, the heat of combustion of dextrose is only about 3 per cent,
more than that of lactic acid. He concludes that the precursor
which yields lactic acid is a body of greater energy than dextrose.
This, of course, does not preclude the possibility that the complex,
whatever it is, from which lactic acid is liberated, contains a carbo-
hydrate group. But it would not be profitable to pursue these
speculations at present. The facts just mentioned suggest that it
is the same precursor which yields the lactic acid developed with
the onset of rigor. Further evidence of the close relations between
the chemical changes occurring in contraction and those occurring
in rigor will be developed in considering the latter phenomenon.
The Substances metabolized in Muscular Contraction. — If the
liberation of lactic acid were assumed to be the immediate cause of
the mechanical changes in muscular contraction, if the nature of
the body which yields lactic acid were known, and if it were proved,
which is far from being the case, that the whole of the energy con-
77* THE PHYSIOLOGY OF THE CONTRACTILE TISSUES
cerned in initiating and carrying out the mechanical effect is derived
from the decomposition of this precursor, the question would still
confront us, What are the materials at the expense of the energy
of which the muscle is restored to its original condition ready for
another contraction ? If the lactic acid is used over and over
again, it is indeed the metabolism of these substances which will
be chiefly represented in the waste products given off by the muscle ;
the lactic, acid complex will merely represent a chemical machine
through which the energy of these other substances is transformed
into mechanical energy, and they will constitute the ultimate source
of energy of the muscular contraction. In this sense the muscular
glycogen, whether it yields lactic acid or not, is almost certainly
one source of energy for the active muscle, being converted into
dextrose, of course, before utilization. Dextrins and maltose, the
intermediate products of this decomposition, have been detected
in muscle, more maltose, indeed, than dextrose being present
(Osborne), since the dextrose is rapidly oxidized. Glycogen cannot
be the only source of muscular energy, for its amount is too small.
For example, the heart of an average man, which weighs 280 grammes,
contains about 60 grammes of solids, and among these certainly not
more than i gramme of glycogen. In twenty-four hours it produces
120 calories of heat (pp. 138, 688), equivalent to the complete com-
bustion of a little less than 30 grammes of glycogen. To supply this
amount, the whole store of glycogen in the heart would have to be used
and replaced every fifty minutes. But the accumulation of glycogen
is immensely slower in the muscles of a rabbit made glycogen-free by
strychnine, and therefore we have to look around for some other source
of energy to supplement the glycogen. We have already brought
forward evidence (p. 610) that, under ordinary circumstances, not a
great deal, at any rate, of the energy of muscular contraction comes
from the proteins. Of carbo-hydrates, the only one except the glycogen
of the heart muscle which is at all adequate to the task of supplying so
much energy is the dextrose of the blood. The quantity of blood
passing through the coronary circulation has been estimated at 30 c.c.
per 100 grammes of cardiac muscle per minute (Bohr and Henriques),
which would be equivalent for an average man to about 120 litres in
twenty-four hours. This quantity of blood will contain at least
1 20 grammes of dextrose, and about 32 grammes will suffice to supply
all the heat produced by the heart. There is no reason to suppose that
this dextrose must first be changed into muscular glycogen, which only
represents a certain amount of reserve carbo-hydrate. Of proteins a
little less than 30 grammes would be needed, of fat a little more than
12 grammes. We see, therefore, how intense must "be the metabolism
that goes on in an actively contracting muscle. On any probable
assumption as to the source of muscular energy, a quantity of material
equal to half of its solids must be used up by the heart in twenty-four
hours. Or, to put it in another way, the heart requires not less than
two-fifths of its weight of ordinary solid food in a day. The body as a
whole requires £$ to ^ of its weight.
The general conclusions to which physiologists have been led
as to the relative importance of the different food substances for
CHEMICAL PHENOMENA OF MUSCULAR CONTRACTION 773
muscular work have been previously given (p. 612), and need not
be repeated here. It may be added that the various food substances
yield muscular energy in isodynamic relation. In other words, a
given amount of muscular work requires the expenditure of approxi-
mately the same quantity of chemical energy, whether it comes
almost entirely from protein, or chiefly from carbo-hydrates, or
chiefly from fat. Some observers have stated that the taking of
even a comparatively small quantity of sugar vastly increases the
capacity for muscular work as measured by the ergograph (p. 750).
But although it is not to be doubted that sugar is under normal
circumstances one of the most important substances used up in
muscular contraction, the claim that sugar is, par excellence, the
food for muscular exertion has not yet been made out.
Physico-Chemical Conditions of Muscular Contraction. — For excised
fresh muscle A (p. 427) has been estimated at 0-68° C. But this is
probably higher than in the living body, for after excision waste products,
with their relatively small and numerous molecules, are still for a time
produced, and are no longer removed by the blood. In salt solutions
isotonic with the muscle substance — e.g., for the frog's gastrocnemius
at room-temperature a 0-75 per cent, solution of sodium chloride — the
resting muscle neither gains nor loses water for some hours. The active
muscle behaves quite differently. When a muscle immersed in isotonic
salt solution is tetanized, water enters it, leading to an increase in
weight and a diminution in specific gravity (Ranke, Loeb, Barlow).
The same occurs even when blood is circulated through active muscles,
the blood becoming poorer in water (Ranke). This may be explained
by the increase of osmotic pressure in the muscle substance which must
accompany the decomposition of large molecules into small. As fatigue
progresses, a movement of water in the reverse direction occurs, and
the muscle rapidly loses water. Exposure of the fatigued muscle for a
sufficient time to an atmosphere of oxygen restores the osmotic proper-
ties of the resting muscle. Striking differences have also been demon-
strated in the behaviour of resting and fatigued muscle to hypotonic
solutions or water. Hales observed long ago that, on injecting large
quantities of water into the bloodvessels of a dog, so as to replace the
blood, marked swelling of the muscles occurred. This physiological fact
is well known to the pork-butchers in China, who have given it a
practical, if not a very praiseworthy, application in sophisticating their
product by increasing its weight (MacGowan).
So long as the muscular fibres are uninjured they are permeable or
impermeable for exactly the same compounds as other animal and
vegetable cells. All substances easily soluble in media like ether or
olive oil readily penetrate them (Overton). To most salts they are
relatively impermeable, as is shown by the fibres retaining their original
volume in isotonic solutions of them. In particular, they cannot easily
take up or retain the salts of the blood-plasma, otherwise the observed
qualitative differences — e.g., the preponderance of potassium in the
muscle and sodium in the plasma — could not be maintained. There are
facts which indicate that temporary changes in the permeability to ions,
not only of muscular fibres, but also of nerve fibres and other excitable
structures, are concerned in their stimulation. Potassium salts after a
time seem to produce an effect upon frog's muscle, which alters its
permeability so that it takes up water from hypertonic solutions.
774
Calcium salts have the opposite effect (Loeb). Sodium (and in a minor
degree lithium) salts have a peculiar relation to the contraction of
skeletal muscle, for which they appear to be indispensable. Yet sodium
chloride produces a paralyzing action on the frog's motor nerve-endings,
so that after perfusion with a solution of that salt stimulation of the
motor nerve causes no contraction, or with a slighter degree of paralysis
contraction only after a long interval. The effect can be counteracted
by solutions containing calcium salts (Locke, Gushing).
Rigor Mortis. — When a muscle is dying, its excitability, after
perhaps a temporary rise at the beginning, diminishes more and
more until it ultimately responds to no stimulus, however strong.
The loss of excitability is not in itself a sure mark of death, for,
as we have seen, an inexcitable muscle may be partially or com-
pletely restored; but it is followed, or, where the death of the muscle
takes place very rapidly, perhaps accompanied, by a more decisive
event, the appearance of rigor. The muscle, which was before soft
and at the same time elastic to the touch, becomes firm; but its
elasticity is gone. The fibres are no longer translucent, but opaque
and turbid. If shortening of the muscle has not been opposed, it
may be somewhat contracted, although the absolute force of this
contraction is small compared with that of a living muscle, and a
slight resistance is enough to prevent it. The reaction is now
distinctly acid to litmus. This is rigor mortis, the death-stiffening
of muscle.
An insight into the real meaning of this singular and sometimes
sudden change was first given by the experiments of Kiihne. He
took living frog's muscle, freed from blood, froze it, and minced it
in the frozen state. The pieces were then rubbed up in a mortar
with snow containing I per cent, of common salt, and a thick neutral
or alkaline liquid, the ' muscle-plasma,' was obtained by filtration.
This clotted into a jelly when the temperature was allowed to rise,
but at o° C. remained fluid. The clotting was accompanied by a
change of reaction, the liquid becoming acid. An equally good,
or better, method is to use pressure for the extraction of the plasma
from the frozen fragments of muscle. A low temperature is essential,
otherwise the plasma will coagulate rapidly within the injured
muscle. A similar plasma can be expressed from the skeletal
muscles of warm-blooded animals (Halliburton), and with greater
difficulty from the heart.
When the muscle, after exhaustion with water, is covered with a
solution of a neutral salt, a 5 per cent, solution of magnesium sulphate
or 10 per cent, solution of ammonium chloride being the best, certain
proteins are extracted which clot or are precipitated much in the same
way as the muscle-plasma obtained by cold and pressure; and the
process is hastened by keeping them at a temperature of 40° C.
In the extracts of mammalian muscle three chief proteins are present :
paramyosinogen (v. Furth's myosin), coagulating by heat at 47° to
50° C. ; myosinogen (v. Fiirth's myogen), coagulating at 55° to 60° C.,
usually about 56°); and serum-albumin, coagulating about 73°. The
CHEMICAL PHENOMENA OF MUSCULAR CONTRACTION 775
serum-albumin belongs to the blood and lymph, and is not a constituent
of the muscle-fibre. The most recent work on the subject is that of
Botazzi, who obtained muscle juice without the addition of water or
salt solutions, by rubbing muscles up with sand, and then subjecting the
triturated material to a pressure of many atmospheres. He finds that,
leaving out of account the serum-albumin, muscle juice contains only
one protein in solution, and this corresponds upon the whole in its
properties to myosinogen. A second protein, and only these two have
been proved to exist in muscle juice, is not in solution, but in the form
of very fine granules revealed by the ultramicroscope. This corresponds
in a general way to paramyosinogen. Botazzi supposes that it repre-
sents the substance of the muscular fibrils. The granules show a ten-
dency even at the ordinary temperature to agglutinate and to be pre-
cipitated. The process is hastened by dilution with water, removal of
the salts by dialysis, addition of acids, and the agglutination and pre-
cipitation are accomplished very rapidly at 45° to 55° C., giving rise
to ' heat coagulation.' The protein in solution (myosinogen) is in-
soluble in distilled water when thoroughly freed from salts, and is pre-
cipitated by dialysis, but not so easily as paramyosinogen. The total
proteins in the juice obtained by pressure varied from 5-3 to 9-5 per
cent., a great deal of the muscle protein being, of course, left in the
residue. The granules (paramyosinogen) constituted from a third to
two-thirds of the protein in different experiments, and the true pro-
portion must have been considerably higher, since on account of their
small size the loss in separating them by filtration was great. The
' myosin ' precipitate, which rapidly forms in muscle-plasma at body
temperature, is sometimes called the muscle-clot, and the liquid which
is left the muscle-serum, but it would probably be better to avoid these
terms, as they suggest an analogy with the coagulation of blood-plasma,
which is apt to be misleading. A similar precipitate or clot seems to
be formed in the interior of the muscular fibres in natural rigor and in
the rapid rigor produced by heating a muscle to a little above the body-
temperature. But in natural rigor the whole of the paramyosinogen
and myosinogen do not undergo the change, since a certain amount of
these substances can as a rule be extracted from dead muscle by saline
solutions. Thus, in rabbit's muscles, before the onset of rigor mortis,
87-3 per cent, of the total protein was found to be soluble in 10 per cent,
ammonium choride solution, and only 12-7 per cent, coagulated; while
after rigor had occurred, 71-5 per cent, was coagulated, and only 28-5 per
cent, remained soluble (Saxl). It is not known whether in the living
muscle paramyosinogen and myosinogen exist as such. It has, indeed,
been stated that, if a tracing is taken from a muscle which is gradually
heated, it first shortens at the temperature of coagulation of para-
myosinogen, and then again at that of myosinogen, and that in frog's
muscle there is an additional shortening at 40°, the temperature at
which in extracts an additional heat precipitate occurs. The conclusion
has been drawn that these substances must be present as such in the
living fibres, and that the successive shortenings are mechanical phe-
nomena due to their heat coagulation. Similar shortenings have been
described in nerve and liver tissue at about the temperatures at which
the proteins in extracts of these tissues are coagulated by heat. But
Meigs has shown that the supposed correspondence is far from being
exact, and that muscles whose proteins have been already coagulated in
a mixture of alcohol and salt solution still show the typical shortening
on being heated. The heat shorter ing is, therefore, dependent on
some other process than aggregation of the particles of coagulable
protein.
776 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES
Certain analogies between rigor and muscular contraction were
early pointed out. In both there is (i) shortening; (2) heat-pro-
duction; (3) formation of lactic acid; (4) discharge of carbon
dioxide; (5) electrical changes. As regards the production of lactic
acid, there is reason to believe that the process is fundamentally
the same as in contraction, and the study of rigor, especially of
certain of the artificially induced forms — e.g., heat rigor — in relation
to the liberation of lactic acid, carbon dioxide, and heat, has thrown
light upon the changes normally occurring in muscle. Another
analogy might be forced into the list by anyone who was deter-
mined to see only rigor in contraction: the rigor passes off as the
contraction passes off, although the ' resolution ' of a rigid muscle
takes days, the relaxation of an active muscle a fraction of a second.
The disappearance of rigor is not dependent on putrefaction; it
takes place when growth of bacteria is prevented (Hermann).
Possibly it is connected with autolytic processes due to intracellular
ferments (p. 599).
Why does coagulation of myosin occur at the death of the muscle ?
To this question no clear answer can be given. Some have looked
on the process as analogous to the clotting of blood when it is shed,
and it has even been suggested that just as a fibrin ferment is
developed when the leucocytes and blood-plates begin to die, a
myosin ferment, which aids coagulation, is developed in dead or
dying muscle. But no proof has been given of the existence of such
a ferment. And it is easy to make too much of the apparent
analogy between the clotting of muscle and the clotting of blood,
for there are differences as well as resemblances. For instance, the
addition of potassium oxalate does not prevent coagulation of
muscle extracts, as it does of blood and blood-plasma. If the
development of lactic acid in the muscle is not the primary cause
of the coagulation which constitutes the essential feature of rigor
mortis, it seems to be closely related to it. For when excised
muscles are abundantly supplied with oxygen, no lactic acid
accumulates in them, and the final loss of excitability of the muscle
is not followed by rigor. In any case, direct precipitation of
hitherto unclotted muscle proteins may be induced by the acid, or
the acid salts formed in its presence. Deficiency of oxygen is
associated with the occurrence of rigor mortis, as it is with the
accumulation of lactic acid, and a developing rigor can be abolished
by oxygen, and its onset long or indefinitely delayed. When strict
aseptic technique is observed an excised sartorius muscle of the
frog may remain irritable in sterile Ringer's solution, even without
oxygenation, for as long as three weeks (Mines).
Various influences affect the onset of rigor. Fatigue hastens
it; heat has a similar effect; the contact of caffeine, chloroform,
and other drugs causes most pronounced and immediate rigor,
CHEMICAL PHENOMENA OF MUSCULAR CONTRACTION 777
Blood applied to the cross-section of a muscle first stimulates the
fibres with which it is in contact, and then renders them rigid.
But it is to be remembered that normally the blood does not come
into direct contact even with the sarcolemma, much less with its
contents.
The effect of heat is of special interest. A skeletal muscle of
a frog, like the gastrocnemius, if dipped into physiological saline
solution at 40° or 41° C. goes into rigor at once; the frog's heart
requires a temperature 3° or 4° higher; the distended bulbus aortae
can withstand even a temperature of 48° for a short time. An
excised mammalian muscle passes into immediate rigor at 45° to
50°. In heat rigor the reaction of the muscle becomes strongly
acid owing to the formation of lactic acid, and the evolution of
carbon dioxide is also increased.
The total discharge of carbon dioxide in heat rigor induced at 40°
amounts to 35 to 40 c.c. per 100 grammes of muscle. An additional
15 to 20 per cent, is obtained on heating to 75° C. to completely coagu-
late the proteins, and a further 15 to 20 per cent, on heating to about
100° C. When a muscle is scalded by being suddenly immersed in
boiling salt solution, lactic acid is not formed, but carbon dioxide to the
amount of 60 to 70 per cent, is discharged. An excised muscle kept in
oxygen for many hours, during which it has discharged several times
as much carbon dioxide as is ever liberated by heating, still yields the
normal discharge on heating whether to 40° C. or to 100° C. On the
other hand, previous survival in an anaerobic atmosphere (of nitrogen)
reduces greatly or abolishes the yield of carbon dioxide at 40° C.,
although not that at 100° C., the sum of the carbon dioxide given off to
the atmosphere of nitrogen and that given off on heating to 100° C.
being about equal to the total amount which would have been dis-
charged by a freshly-excised muscle on heating first to 40° C. and then
to 100° C. If acid is added to a fresh muscle at about o° C. even more
carbon dioxide is liberated than in heat rigor, while the yield of lactic
acid is, even after many hours, very little increased above the normal
amount for fresh resting muscle. When the acidified muscle after the
discharge of the carbon dioxide is now heated to 40° C., the yield of
lactic acid is increased, but only traces of carbon dioxide are given off.
From these and similar observations, Fletcher concludes that the
carbon dioxide discharged during heat rigor at 40° C. is pre-existent
carbon dioxide set free from carbonates or other compounds by
the lactic acid known to be produced in heat rigor. The carbon
dioxide discharged at 75° and 100° C. he regards as held by
muscle colloids or in combination with amino-acid groups. These
results tend to discredit the ' inogen ' theory (p. 270), with its
assumption that ' intramolecular oxygen ' is stored away in the
muscle, which was largely based upon erroneous observations on
the discharge of carbon dioxide from heated muscles. According
to this theory, carbon dioxide and lactic acid were supposed to arise
from a common precursor into which oxygen had been previously
introduced.
778 THE PHYSIOLOGY OF THE CONTRACTILE TISSUES
The production of heat in heat rigor is also of great interest.
Hill has shown that it amounts to from 0-6 to i-o gramme calorie
per gramme of muscle. Of this no more than 0-05 calorie can be
due to the heat of neutralization of lactic acid by the sodium
bicarbonate in the muscle, with which it reacts as soon as it is
liberated. The rest of the heat is associated with the chemical
reaction by which lactic acid is formed from its precursor, a reaction
which, there is every reason to believe, is the same as that which
occurs in muscular contraction. The heat production can only
be due in very slight degree to the physical alteration (clotting or
precipitation) of the muscle proteins.
The so-called rigor caused by water, which is not a true rigor,
causes no increase in the carbon dioxide given off. Chloroform,
on the other hand, produces a marked increase in the carbon
dioxide production, and this is evidently related to its action in
hastening the onset of rigor. Rigor mortis is to some extent in-
fluenced by the nervous system, for section of its nerves retards
the onset of rigor in the muscles of a limb. Ante-mortem stimula-
tion of the peripheral ends of the vagi, even with currents too weak
to cause a perceptible effect upon the heart-beats, prolongs the
period of spontaneous contraction and the irritability of the ven-
tricles after death, and retards the onset of rigor (Joseph and
Meltzer). Cold rigor is obtained when frog's muscles are cooled
to —15° C. The muscles remain perfectly translucent. They
do not recover their irritability on thawing, but if cooled only to
— 7° C. they recover (Folin).
In a human body rigor generally appears not earlier than an
hour, and not later than four or five hours, after death. In ex-
ceptional cases, however, it may come on at once, and the annals
of war and crime contain instances where a man has been found
after death still holding with a firm grip the weapon with which
he had fought, or which had been thrust into his hand by his
murderer (so-called cataleptic rigor). It is related that after
one of the battles of the American Revolutionary War some of the
dead were found with one eye open and the other closed as in the
act of taking aim. A high temperature favours a rapid onset; a
body wrapped up in bed will, other things being equal, become rigid
sooner than a body lying stripped in a field. Muscular exhaustion,
as we have said, is another favouring condition: hunted animals
and the victims of wasting diseases go quickly into rigor. It is
a rule, but not an invariable one, that rigor, when it comes on
quickly, is short, and lasts longer when it comes on late. All the
muscles of the body do not stiffen at the same time; the order
is usually from above downwards, beginning at the jaws and neck,
then reaching the arms, and finally the legs. After two or three
days the rigor disappears in the same order. The position of the
CHEMICAL PHENOMENA OF MUSCULAR CONTRACTION 779
limbs in rigor is the same as at death; the muscles stiffen without
any marked contraction. This can be strikingly shown on a newly-
killed animal by cutting the tendons of the extensors of one foot
and the flexors of the other ; when natural rigor comes on, the feet
remain just as they were. If heat rigor, however, is caused, the
one foot becomes rigid in flexion and the other in extension; and
the contraction-force is considerable, although not so great as that
of an electrical tetanus in a living muscle.
The Possibility of Recovery of Muscles after Rigor. — When the circu-
lation in the hind legs of rabbits is interrupted by compression or
ligation of the abdominal aorta (Stenson's experiment), the muscles lose
their excitability, but speedily recover, if they have not been deprived
of arterial blood for too long a time, when the blood is again allowed to
reach them. A longer interruption of the circulation leads not only
to total inability to respond to stimulation, but also to rigor, and most
observers are agreed that, as regards the skeletal muscles at least, this
is the irrevocable end of excitability. Brown-Sequard, indeed, stated
that after the full development of rigor in the rabbit's muscles (Stenson's
experiment), and also in the hand of an executed criminal through
which an artificial circulation was established, recovery ensued. But
probably the rigor was incomplete or did not involve all the fibres. In
heart muscle the conditions appear to be somewhat different, and Heubel
has alleged that rhythmical contractions of the frog's heart can be
restored by filling its cavity with blood, after rigor has been caused by
heat and in other ways, and we have already seen that the same is true
of the mammalian heart alter the onset of rigor. Excised frog's
muscles which have undergone rigor mortis become less stiff when
exposed to an atmosphere of oxygen.
CHAPTER XIV
NERVE
THE voluntary movements are originated by efferent or outgoing
impulses from the brain, which reach the muscles along their
motor nerves. The involuntary movements and the secretions
are in many cases able to go on in the absence of central connec-
tions, but are normally under central control. Afferent impulses
are continually ascending to the cord and brain from the skin,
joints, bones, muscles, and organs of special sense like the eye and
the ear. Everywhere the connection between the nervous centres
and the peripheral organs, and between different parts of the
central nervous system, is made by nerve- fibres. Those which
run outside the brain and cord are called peripheral nerve-fibres
to distinguish them from the intracentral fibres of the central
nervous system itself.
In this chapter we propose to consider certain of the general
properties of nerve-fibres. Most of our knowledge of these proper-
ties has been derived from experiments on the peripheral, and
particularly the peripheral motor nerves ; but there is every reason
to believe that the main results are true of all nerve-fibres, afferent
and efferent, peripheral and central.
What we call nerve-fibres were known and named, and many im-
portant facts in their physiology discovered, long before their true
morphological significance was recognized. The researches of recent
years have shown that every nerve-fibre is, as regards its essential con-
stituent the axis-cylinder, a process of a nerve-cell. The nerve-cells,
each of which, including all its processes, may be conveniently termed
a neuron, are the essential elements of the nervous system. The cell-
bodies of most of the neurons are situated in, or in close relation to, the
spinal cord and the brain, and therefore the detailed description of
them will be reserved till we come to treat of the central nervous system
(see p. 850 and Figs. 328 to 340). It is enough to say here that in
general a nerve-cell gives off two kinds of piocesses: (i) one or more
dendrites or protoplasmic processes, which repeatedly bifurcate like the
branches of a tree into thinner and thinner twigs, and extend only for
a relatively short distance from the cell-body; (2) an axis-cylinder
process or axon, which as a rule runs for a considerable distance without
altering its calibre, and either gives off no branches (as in the peripheral
nerves) or only a comparatively small number of lateral twigs (col-
780
THE NERVE-IMPULSE OR PROPAGATED DISTURBANCE 781
laterals). Ultimately the axis-cylinder process and its collaterals, if it
has any, end by breaking up into a brush, a plexus or a feltwork or
basketwork of fibrils. The axons of different nerve-cells vary greatly
in length. Some terminate within the grey matter of the brain or spinal
cord not far from their origin; others run in the white tracts of the
central nervous system or in the peripheral nerves for half the height
of a man. All except the shortest axis-cylinder processes become
clothed at a little distance from the cell-body with a protective covering,
which continues to invest them (and their collaterals) throughout the
rest of their course, disappearing only when they begin to break up at
their terminations. An axis-cylinder process (spoken of simply as the
axis-cylinder, when considered apart from the nerve-cell) constitutes,
with its covering, a nerve-fibre.
The axis-cylinder is the essential conducting part of the fibre, for it is
present in every nerve-fibre, running from end to end of it without break,
and towards the periphery it is alone present. It is made up of fine
longitudinal fibrils embedded in interstitial substance (Fig. 329, p. 851).
Such a fibrillar structure is best shown after treatment of the nerve-
fibres with certain reagents, although it is certain that it exists pre-
formed in the living fibres.
SECTION I. — THE NERVE- IMPULSE OR PROPAGATED DISTURBANCE:
ITS INITIATION AND CONDUCTION.
So far as we know, the only function of nerve-fibres is to conduct
impulses from nerve-centres to peripheral organs, or from peripheral
organs to nerve-centres, or from one nerve-centre to another.
In the normal body these impulses never, or only very rarely,
originate in the course of the nerve- fibres; they are set up either
at their peripheral or at their central endings. By artificial stimu-
lation, however, a nerve-impulse may be started at any part of a
fibre, just as a telegram may be dispatched by tapping any part of
a telegraph wire, although it is usually sent from one fixed station
to another.
Nature of the Nerve- Impulse. — What the nerve-impulse actually
consists in we do not know. All we know is that a change or dis
turbance of some kind, of which the most evident token is an
electrical change, passes over the nerve with a measurable velocity,
and gives tidings of itself, if it is travelling along efferent fibres —
that is, out from the central nervous system — by the contraction
or inhibition of muscle or by secretion; if it is travelling along
afferent fibres — that is, up to the central nervous system — by sensa-
tion, or by reflex muscular or glandular effects.
Whether the wave which passes along the nerve is a wave of
chemical change (such, to take a very crude example, as runs
along a train of gunpowder when it is fired at one end), or a wave
of mechanical change, a peculiar and most delicate molecular
shiver, if we may so phrase it, or a shear in a definite direction along
the colloidal substance of the axis-cylinder (Sutherland), there is
no absolutely definite experimental evidence to decide. An
7&z NERVE
electrical change accompanies the nerve-impulse travelling at the
same rate, and although this is to be distinguished from the impulse
itself, there is little doubt that the latter is essentially connected
with a disturbance of the electrical equilibrium of the nerve-
substance.
An attempt has been made to settle the question by determining the
temperature coefficient of the velocity of conduction of the impulse —
i.e., the quantity which measures the change of velocity for a given
change of temperature. For most physical processes the quotient
velocity at T»+ 10° .
— TT T-~ . where Tn is any given temperature, is not greater
than 1-2, while for frog's sciatic nerve the temperature coefficient for
the most part lies between 2 and 3 (Snyder). The mean value of a
large number of observations is 1-79, with T«= 8° to 9° C. (Lucas). For
the pedal nerve of the giant slug the mean value of the temperature
coefficient is 1-78 (Maxwell). In other words, while for the majority of
physical processes an increase of 10° C. increases the velocity of the
process by at most one-fifth, the same increase of temperature increases
the velocity of conduction of the nerve-impulse by four- fifths, or even
more. While it is true that it may not be entirely safe to apply such a
criterion to a biological process which need not be either entirely chemical
or entirely physical, and very likely is a complex one, the suggestion,
so far as it goes, is undoubtedly in favour of the chemical hypothesis.
That chemical changes go on in living nerve we need not hesitate to
assume; and, indeed, if the circulation through a limb of a warm-
blooded animal be stopped for a short time, the nerves lose their
excitability. Even the nerves of cold-blooded animals gradually
become inexcitable and incapable of conduction when placed in an
oxygen-free medium, as the oxygen already contained in the tissue is
exhausted. The excitability and conductivity of the nerve are restored
by oxygen. It is clear, then, that even a resting nerve requires oxygen,
and it can be shown that the loss of function is acceleiated by stimulation
in the absence of oxygen. But the metabolism is very slight compared
with that in muscle or gland. Until recently even in active nerve no
measurable production of carbon dioxide had ever been observed, nor,
in fact, had any chemical difference between the excited and the resting
state ever been unequivocally made out. However, it has been
announced that by the aid of an extremely delicate method of estimating
small quantities of carbon dioxide, a measurable production of carbon
dioxide can be detected even in resting frogs' nerves, and that this pro-
duction is increased two to three times on stimulation (Tashiro). This
result is somewhat puzzling in view of the fact that neither in cold-
blooded nor in mammalian nerves is there any sensible rise of temper-
ture during stimulation. With the apparatus shown in Fig. 272 (an
electrical resistance thermometer or bolometer whose use depends upon
the fact that the electrical resistance of a metallic conductor varies
with its temperature) an increase even of 0-0003° C. in the temperature
of the sciatic nerves of dogs could not be detected during tetanization.
Rolleston failed to find evidence of a rise of even 0-0002° C. in frog's
nerves during stimulation. And according to the latest investigation
with a more suitable and much more sensitive thermo-electric arrange-
ment, the passage of a single nerve impulse along a frog's nerve cannot
be associated with an increase of temperature in the nerve of even the
hundredth million of a degree (A. V. Hill). The difficulty of inducing
fatigue in nerves under ordinary conditions has been considered a strong
B
THE NERVE-IMPULSE OR PROPAGATED DISTURBANCE 783
support of the physical nature of the conduction process. Neverthe-
less, it is possible to show by special methods that nerve can be tempor-
arily fatigued, although it recovers very rapidly. When a medullated
nerve is stimulated, a brief period ensues during which it refuses to
respond to a second stimulus. This refractory period is normally very
short — not more than 0-002 second for the frog's sciatic. But it can
be greatly prolonged by cold, asphyxia, or anaesthesia, especially by
the alkaloid yohimbine (Tait and Gunn), and when the refractory period
is thus prolonged, fatigue phenomena are readily induced by stimulation.
And while the nerves of warm-blooded animals at body temperature
and those of cold-blooded animals at about 32° C. can hardly be shown
to undergo fatigue when tetanized in atmospheric air, fatigue phe-
nomena are easily elicited when the temperature is lowered even
although air is supplied (Thorner).
Stimulation of Nerve. — With some differences, the same stimuli
are effective for nerve as for muscle (p. 737) ; but chemical stimula-
tion is not in general so easily obtained. The so-called thermal
Fig. 372. — Electrical - Resistance o p
Thermometer (Natural Size) as > ¥ ¥ 3
used for investigating heat-pro-
duction in mammalian nerves in
situ. A, a piece of hard rubber in
the hook-shaped part of which the
fine platinum wire P is fixed, and
covered with insulating varnish;
c, c, thick copper wires connected •
with P, fastened in grooves, and »
covered with paraffin. Above they
end in contact with the small
binding posts, B1P B2. B is a hard
rubber sliding piece, with a slot s.
When B is in position the screw, a,
projects through the slot. By a nut
on this screw B is fixed on A when
the nerve has been arranged in the ^'
groove. P
stimulation is not a real stimulation due to the sudden change of
temperature. The irregular contractions of the muscle caused by
the local application of heat to the nerve are dependent on desicca-
tion of the nerve.
Chemical Stimulation. — When hyper- or hypo tonic solutions are em-
ployed, the withdrawal or entrance of water may be an important factor.
For salts which penetrate the fibres with equal difficulty this factor
can be eliminated by applying them as isotonic solutions. There is
evidence that chemical stimulation proper, as distinguished from the
stimulation produced by changes in the water content of the fibres by
osmosis, is connected with the electrical charges on the dissociated ions
of the salts (p. 428). Electrical stimulation, indeed, may only be a
variety of chemical stimulation (Loeb, Mathews, etc.).
Mechanical Stimulation may be applied to a nerve by allowing a small
weight to fall on it from a definite height or by permitting mercury to drop
upon it from a vessel with a fine outflow tube. A regular tetanus may
thus be obtained. Tigerstedt found that the smallest amount of ,vork
spent on a frog's nerve which would suffice to excite it was a little less
784 NERVE
than a gramme-millimetre — that is, the work done by a gramme falling
through a distance of a millimetre, or (taking an erg as equivalent to
i^rro gramme-centimetre) about 100 ergs. No doubt a great part of
this is wasted, as a much smaller quantity of work done by a beam of
light on the retina or by an electrical current on an isolated nerve, both
of which may be supposed to act more directly on the excitable con-
stituents, suffices to cause stimulation. Thus, the work done by the
minimal, natural or specific, stimulus for the retina in the form of green
light may be as little as — g erg (S. P. Langley), or only one-ten-thousand -
millioneth part of the minimum work necessary for mechanical stimula-
tion. Again, with electrical stimulation (closure of a voltaic cuirent,
or condenser discharges) it has been shown that an amount of work
equal to — 4 erg may be enough to cause excitation of a frog's nerve.
This is ten thousand times as great as the minimal luminous stimulus,
but a million times less than the minimal mechanical stimulus.
The laws of electrical stimulation for nerve are essentially the same
as those we have already discussed for muscle (p. 741). The voltaic
current stimulates a nerve, as it does a muscle, at closure and opening.
During the flow of the current, so long as its intensity remains constant,
there is as a rule no excitation, or at least none which is propagated
along the nerve, so that the muscles supplied by it remain uncontracted.
But under certain conditions — for example, when the nerve is more
excitable than usual (as is the case with nerves taken from frogs which
have been long kept in the cold) — a closing tetanus may be seen while
the current continues to pass through the nerve, and an opening tetanus
after it has ceased to flow, just as when the current is led directly
through the muscle. Sensory nerve-fibres, too, are stimulated by a
voltaic current during the whole time of flow. Induction shocks are
relatively more powerful stimuli for nerve than the make or break of a
voltaic current. The opposite, as we have seen, is true of muscle; and,
upon the whole, we may say that muscle is more sluggish in its response
to stimuli, and is excited less easily by very brief currents, than nerve
is. An apparent illustration of this difference is the fact that the
nervous excitation has no measurable latent period, while muscular
excitation has. But it is quite possible that, if the conditions of experi-
ment were as favourable in nerve as in muscle, a sensible latent period
might be found here too.
In nerve as in muscle, strength of stimulus and intensity of response
correspond within a fairly wide range, when we take the height of the
muscular contraction or the amount of the negative variation (p. 824)
as the measure of the nervous excitation. Summation of stimuli, super-
position of contractions, and complete tetanus, are caused by stimulating
the muscle through its nerve, just as by stimulating the muscle itself
(p. 756).
Excitability of Nerve. — It has usually been stated that the ex-
citability of frog's nerve, as measured by the muscular response to
stimulation, is increased by rise of temperature, and diminished by
fall of temperature. It has, however, been shown that this increase
of excitability is only apparent, and due to the strengthening of
the current by diminution of the resistance, since the resistance
of all animal tissues, like that of electrolytic conductors in general,
diminishes as the temperature rises (Gotch). When precautions
THE NERVE-IMPULSE OR PROPAGATED DISTURBANCE 785
are taken to keep the current intensity the same at the various
temperatures compared, it is found that cooling of a (frog's) nerve,
even to 5° C., increases the excitability for currents of long duration
(several hundredths of a second). It has, indeed, been shown both
for muscle and for nerve that the cooler tissue requires a smaller
current strength for its excitation when the current is of long dura-
tion. With brief currents this effect is masked, either partially or
completely, by the greater increase of current strength needed in the
case of the cooler tissue to compensate fora given decrease in duration
(p. 789) (Lucas and Mines). This is the reason that for induction
shocks or voltaic currents of short duration, the excitability of the
nerve seems to be increased by a rise of temperature (up to about
30° C. in the case of frog's nerve), and diminished by cooling.
Drying of a nerve at first increases its excitability; and the same
is true of separation of a nerve from its centre. In the latter case
the increase of irritability begins at the proximal end of the nerve,
and travels towards the periphery. As time goes on, the excita-
bility diminishes, and ultimately disappears in the same order
(Ritter-Valli Law). At a certain stage it may be found that a
given stimulus causes a smaller and smaller contraction the farther
down the nerve — that is, the nearer to the muscle — it is applied.
On this was based the now abandoned ' avalanche theory/ according
to which the impulse continually unlocked new energy as it passed
along the nerve, and so gathered strength in its course like an
avalanche. It is now known that no material change takes place
in the intensity of the excitation while it is being propagated along
a normal uninjured nerve. For instance, experiments on the
phrenic nerve, in its natural position, and with all its connections
intact, have shown that with a given strength of stimulus the
amount of contraction of the diaphragm is the same whether the
nerve be excited in the upper, middle, or lower portion of its course.
In the above experiment on the isolated, and therefore injured,
nerve, the contraction varies in height with the distance of the
point of stimulation from the muscle, not because the excitation
grows as it travels, but because it is already greater at the moment
when it sets out from a point near the central end of the nerve
than at the moment when it sets out from a point near the muscle.
Electrotonus. — Although the constant current does not, unless
it is very strong or the nerve very irritable, cause stimulation during
its passage, it modifies profoundly the excitability and conductivity
of the nerve. In the neighbourhood of the kathode the excitability
is increased (condition of katelectrotonus), while around the anode
it is diminished (anelectrotonus). Immediately after the opening
of the current these relations are for a brief time reversed, the
excitability of the post-kathodic area (area which was at the kathode
during the flow) being diminished, and that of the post-anodic
50
786
NERVE
increased. In the intrapolar area there is one point the excita-
bility of which is not altered. This indifferent point, as it is called.,
shifts its position when the intensity of the current is varied, moving
towards the kathode when the current is increased, towards the
anode when it is diminished.
It is only under certain definite conditions that these phenomena, first
described by Pfluger, appear in their purity and uncomplicated by other
changes. The nerve should be quite fresh, the current a weak or at
most a moderately strong one, and the stretch of nerve employed
should be as far as possible from the cross section, and from the cross
sections of branches. The middle region of the frog's sciatic nerve is
the best. When all these conditions are fulfilled, the whole stretch
of nerve in katelectrotonus — i.e., the part on both sides of the kathode
and at the kathode itself shows an increased stimulation effect, the
more pronounced the nearer to the kathode the point of stimulation.
This condition, however, only lasts an instant. Then the excitability
begins to sink sharply first at the kathode, then on both sides of it, till
it ultimately becomes decidedly less than
the initial excitability. This secondary
depression of excitability, always most
marked at the very kathode, is just as con-
Fig. 273 . — Katelectrotonus. Weak
tetanus of muscle (the right-hand
elevation), greatly intensified in
katelectrotonus of the motor nerve
(th« left-hand elevation).
Fig. 274. — Anelectrotonus. Strong
tetanus of muscle (left-hand ele-
vation), lessened in strength by
anelectrotonic condition of the mo-
tor nerve (right-hand elevation).
stant a phenomenon as the preliminary increase. The stronger the cur-
rent the more profound is the depression, the more quickly it is de-
veloped, and the greater is the distance to which it spreads along the
nerve. With a certain strength of current the depression appears so
rapidly that the preliminary increase of excitability may be completely
missed. When the current is opened the excitability quickly increases
again, but with strong currents it may remain depressed for a while. At
the anode changes in the reverse direction may be observed, although
they are less pronounced than at the kathode. Thus at the anode
during the passage of the current the initial depression of the excitability
tends to give place to an increase (Werigo).
These statements have been made on the strength of experiments in
which the height of the muscular contraction was taken as the index of
the excitability of the nerve at any given point. It is difficult, however,
to disentangle the effects of alterations in the excitability from the
effects of alterations of conductivity — i.e., of the power of a portion of
the nerve to conduct an impulse set up elsewhere. Whether these two
properties are distinct or not is a question which will be considered a
little later on. But it is perfectly clear that in deducing conclusions
THE NERVE-IMPULSE OR PROPAGATED DISTURBANCE
as to the effect produced on a nerve by excitation at a given point from
the resultant effect on the muscle to which the nerve is attached (or
on a galvanometer or electrometer if we are following the effect by
means of the electrical changes), we must know whether the change
set up in the nerve at the
point of excitation can pass
freely along the nerve to the
muscle or to the point at
which it is led off to the
galvanometer. Now, changes
of conductivity are certainly
produced in a nerve by the
constant current, which even
outlast its flow. For all
currents above a certain
strength the conductivity at
the kathode and in its neigh-
bourhood is eventually dim-
inished, and with currents
still only moderately strong
the block deepens into im-
passability. The conduc-
tivity at the anode is, during
this stage, higher than at the
kathode, so that at the time
of full kathodic block the
nerve - impulse still passes
through the region around
the positive pole. With still
stronger currents the con- 275._Diagram Of Changes of Excitability
ductivity here, too, dimm- and Conductivity produced in a Nerve by a
Voltaic Current. E, changes of excitability
during the flow of the current, according to
Pfliiger. These are seen most typically with
the weaker currents. In particular the in-
creased excitability at and around the kathode
when the current is strong very quickly gives
place to depression. The ordinates drawn
from the abscissa axis to cut the curve repre-
sent the amount of the change. C(i), changes
of conductivity found shortly after the closure
and during the flow of a moderately strong
current. Conductivity greatly reduced around
kathode; little affected at anode. C(2),
changes of conductivity during flow of a very
strong current. Conductivity reduced both in
anodic and kathodic regions, but less in the
former. C1, changes of conductivity just after
opening a moderately strong current. Con-
ductivity greatly reduced in region which was
formerly anodic; little affected in region for-
merly kathodic.
ishes, until the anode as well
as the whole intrapolar re-
gion is blocked. After the
opening of the current, the
relation between kathodic
and anodic conductivity is
reversed, for now the post-
kathodic region conducts the
nerve-impulse relatively bet-
ter than the post -anodic. It
will be seen that these
changes of conductivity up-
on the whole run parallel to
the (secondary) changes of
excitability, depression of
excitability correspond ing to
depression of conductivity,
and vice versa. With the
relatively strong currents re-
quired to produce decided
effects on the conductivity,
any preliminary change in the same sense as the (so-called primary)
effects on the excitability (increase at kathode, decrease at anode)
might be expected to be fleeting, and therefore less easy to detect.
The above facts serve to explain the manner in which the effects of
stimulation of a nerve with the constant current vary with the strength
788
NERVE
and direction of the stream. These effects, so far as the contraction of
the muscles supplied by the nerve is concerned, have been formulated
in what has been somewhat loosely termed the law of contraction. In
this formula the direction of the current in the nerve is commonly dis-
tinguished by a thoroughly bad but now ingrained phraseology, as
ascending when the anode is next the muscle, and descending when the
kathode is next the muscle.
Current.
Ascending.
Descending.
M.
B.
M.
B.
Weak -
C
C
Medium -
C
C
C
C
Strong -
C
C
—
Here M means ' make,' B, ' break,' of the current; C means ' con-
traction follows.'
The explanation generally given is as follows: Wherever there is an
increase of excitability sufficiently rapid and sufficiently large, stimula-
tion is supposed to take place; where there is a fall of excitability,
stimulation does not occur. Accordingly, at closure the kathode stimu-
lates— the anode does not; while at opening, the anode, at which the
depressed excitability jumps up to normal or more, is the stimulating
pole; the kathode, at which it declines to normal or under it, is inactive.
With a weak current, (i) contraction only occurs at make, and (2) the
direction of the current is indifferent. The explanation of the first fact
is that the make is a stronger stimulus than the break, and when £he
current is weak enough the break is less than a minimal stimulus. No
sensible change of conductivity is caused by weak currents, which
suffices to explain (2).
With a ' medium ' current, contraction occurs at make and break with
both directions. Heie the break excitation is effective as well as the
make. With anode next the muscle (ascending current), there is, of
course, nothing to prevent the opening excitation, which starts at the
anode, from passing down the nerve and causing contraction ; and since
there is no block around the anode or in the intrapolar region with
' medium ' currents, there is nothing to keep the closing (kathodic)
excitation from reaching the muscle too. With the kathode next the
muscle (descending current), the closing excitation, which starts from
the kathode, has no reigon of diminished conductivity to pass through,
nor has the opening (anodic) excitation, for the kathodic block, caused by
moderately strong currents, is removed as soon as the current is broken.
With ' strong ' currents there are only two cases of contraction out
of the four, just as with ' weak,' but for very different reasons. There
is a break-contraction with ascending, and a make-contraction with
descending current. With ascending current the anode is next the
muscle, and the break-excitation starting there has nothing to hinder
its course. The make-excitation, although as strong or stronger, has to
pass through the whole intrapolar region and over the anode, and here
the conductivity is depressed and the nerve-impulse blocked. With
descending current the kathode is next the muscle, and there is no
hindrance to the passage of the make-excitation. The break-excitation,
however, has to traverse the whole intrapolar region, and this does not
THE NERVE-IMPULSE OR PROPAGATED DISTURBANCE 789
at once, after a strong current, become passable. The break-excitation,
accordingly, cannot get through to the muscle.
A formula similar to the law of contraction has been shown to hold
for the inhibitory fibres of the vagus (Bonders) , ' inhibition ' being
substituted for ' contraction.' There is also some evidence that a
similar law obtains for sensory nerves.
It is not difficult to see that with currents of brief duration the break
follows so quickly on the make that interference of their opposed effects
may occur. This is the reason — or, at least, one reason — why, ; bove
a certain frequency, a muscle or nerve ceases to respond to all of a
series of rapidly recurring electrical stimuli (p. 758). It is also the
reason why, with single very brief stimuli, a greater current intensity
must be employed in order to cause excitation than when the duration
of the stimulating current is greater (Wood worth, Lucas).
The Law of Contraction for Nerves ' in Situ.' — When a nerve is stimu-
lated without previous isolation — in the human body, for instance,
through electrodes laid on the skin — the current will not enter and
leave it through definite small portions
of its sheath, nor will it be possible to
make the lines of flow nearly parallel to
each other and to the long axis of the
nerve, as is the case in a slender strip of
tissue when there is a considerable dis-
tance between the electrodes.
On the contrary, when, as is usual in
electro-therapeutical treatment, a single
electrode — say, the positive — is placed
over the position of the nerve, and the
other at a distance on some convenient
part of the body, the current will enter
the nerve by a broad fan of stream-lines
cutting it more or less obliquely, and pass
out again into the surrounding tissues;
so that both an anode (surface of en-
trance) and a kathode (still larger surface
of exit) will correspond to the single
positive pole. Similarly, the single nega-
tive electrode will correspond to an
anodic surface where the now narrowing
sheaf of lines of flow enters the nerve, and
a smaller kathodic surface, where they emerge. Even if the two elec-
trodes were on the course of the nerve, the stream-lines would still cut
it in such a way that each electrode would correspond both to anode and
kathode (Fig. 276).
It is impossible under these circumstances to take account of the
direction of a current in a nerve, or to connect direction with any specific
effect. When we place one of the electrodes over the nerve and the
other at a distance, the law of contraction only appears in a disguised
form; for since a kathode and an anode exist at each pole, there is, with
a current of sufficient strength (' strong current '), excitation at each,
both at make and break. The negative make contraction is, however,
stronger than the positive, for the excitation corresponding to the latter
arises at the secondary kathodic surface, where the sheaf of current-lines
spreading from the positive electrode passes out of the nerve. Now,
this is much larger than the primary kathodic surface, through which
the narrow wedge of stream-lines passes to reach the negative electrode,
and the current density at the latter is accordingly much greater. The
Fig. 276. — Diagram of Lines of
Flow of a Current passing
through a Nerve. A, an isolated
nerve ; B, a nerve in situ. Secon-
dary anodes ( + ) are formed
where the current re-enters the
nerve below the negative elec-
trode after passing through the
tissues in which it is embedded
and secondary kathodes ( - )
where the current passes out of
the nerve into the surrounding
tissues below the positive elec-
trode.
790 NERVE
positive break-contraction is, for a similar reason, stronger than the
negative.
With a ' weak ' current, the only contraction is a closing one at the
kathode; with a ' medium ' current there are both opening and closing
contractions at the positive pole, and a closing but no opening con-
traction at the negative (Practical Exercises, p. 846).
Conductivity of Nerve. — The disturbance which is called the
nerve-impulse, once set up, is propagated along the fibres. Are
the changes in the nervous substance involved in the initiation of
the disturbance at a given point identical with those involved in
its transmission from one point to the next, or are they different ?
This is a question which has been much discussed, and many
attempts have been made to prove that the two processes can be
dissociated by acting on nerves with substances like carbon dioxide,
ether, and alcohol, which gradually suspend their functions, by
cutting nerves off from the circulation and allowing them to die
gradually, by depriving them of oxygen and in other ways. Many of
the results obtained from such experiments seem at first sight to
be favourable to the view that the local change is different from the
propagated disturbance. Nevertheless, careful examination of the
results on which such statements are based indicates that none of
them supplies a crucial test of the question at issue. For example,
when a stretch of frog's sciatic nerve is treated with ether or another
of the narcotics which act on nerve, and the strength of stimulus
determined which is necessary to elicit a contraction when applied
to an untreated portion more remote from the muscle than the
narcotized area, this strength is found, for some time after the
application of the narcotic, to be just the same as it was previous
to the application. ' The conductivity ' of the narcotized stretch
appears to be unaltered. On the othxar hand, the stimulus, when
applied within the narcotized region, must be strengthened, and
the narcotic appears to have diminished the ' excitability ' of the
nerve. When the narcotic has acted for a longer time, the reverse
effect appears. No stimulus, however strong, applied to the central
non-narcotized stretch will cause a contraction, the ' conductivity '
having been apparently totally abolished by the narcotic, whereas
a strong stimulus applied in the narcotized region will still cause
a contraction, showing that ' excitability ' still remains. As to
the facts there is general agreement; it is their interpretation
which is in doubt. Now, it has been shown that in passing along
a narcotized nerve the propagated disturbance diminishes in pro-
portion to the length of nerve which it has to traverse. Accordingly
in the second stage of narcosis the failure of the stimulus applied
to the upper part of the nerve to elicit a contraction is explained
most naturally as due to the extinction of the disturbance, which
must pass through the whole narcotized region, whereas the dis-
turbance set up by stimulation in that region succeeds in reaching
THE NERVE-IMPULSE OR PROPAGATED DISTURBANCE 79i
the muscle, since it has a shorter stretch of narcotized nerve to
traverse. This experiment, then, in reality affords no proof that
excitability and conductivity can vary independently. Facts are
also known, to which allusion need not be made here, but which
greatly modify the ordinary interpretation of the experimental
results obtained in the first stage of narcosis, and upon the whole
it may be said that these direct methods of determining the question
have failed to yield a satisfactory answer. Indirect evidence
exists, however, that the local process initiated by stimulation is
not quite the same as the process involved in the propagation of
the disturbance (Lucas); Thus, a brief current too weak to set up a
propagated disturbance, nevertheless causes so me change at the pomt
of stimulation, since a second current, also too weak to be effective
by itself, will, when thrown in a short time after the first, cause
a disturbance which is propagated along the nerve. There is good
reason to believe that the change produced by the first current is
not the same in kind as that produced by the second, only weaker,
but that it is inherently different in quality. Above all, it is a
local change incapable of being itself propagated, but constituting
the necessary prelude to the starting of the propagated disturbance.
Lucas has called this preliminary local effect the ' local excitatory
process.'
There are many facts which indicate that the capacity of different
functional or anatomical groups of nerve-fibres for responding to stimu-
lation and for conducting the nerve-impulse can be differently affected
by one and the same influence. For example, pressure abolishes the
conductivity of sensory fibres sooner than that of motor fibres.
Cocaine locally applied to a nerve diminishes or abolishes its con-
ductivity, according to the dose. It exercises a selective action as
regards nerve-fibres of different kinds, picking out and paralyzing
sensory fibres before motor; vagus fibres conducting upwards before
those conducting downwards, vaso-constrictors before vaso -dilators,
and broncho-constrictors before broncho-dilators (Dixon).
The conduction or propagation of a definite disturbance or impulse is
a phenomenon not confined to nervous tissue. It is also characteristic-
ally seen in muscle, although there the mechanical effect which con-
stitutes the normal response to the arrival of the propagated disturbance
obtrudes itself and tends to divert attention from the latter. It is
unlikely that the conduction process in muscle should be essentially
different from that in nerve, and in muscle, as in nerve, there is
evidence that it is associated with only a small, perhaps not even a
detectable, liberation of heat. The main heat-production in muscle
is essentially a feature not of conduction, but of contraction. Con-
duction in muscle can be completely dissociated from the contraction
process in various ways. For example, if a portion of a muscle is
immersed for a time in distilled water, so-called water rigor ensues, and
the altered muscle has lost the power of contraction. It will never-
theless conduct the impulse which on reaching the unaltered part of the
muscle causes it to contract normally.
Double Conduction. — When a nerve (or muscle) is stimulated
artificially, the excitation runs along it in both directions from the
792 NERVE
point of stimulation; so that nerve-fibres which in the intact body
are afferent can conduct- impulses towards the periphery and
efferent fibres can conduct impulses away from the periphery. In
the normal state, however, double conduction must seldom occur,
for efferent fibres are connected centrally, and afferent fibres
peripherally, with the structures in which their natural stimuli
arise. In general, too, an impulse, if it did pass centrifugally along
an afferent fibre, would not give any token of its existence, for the
peripheral organ would not be able to respond to it; and there is no
ground for assuming that the central mechanisms connected with
afferent fibres are better fitted to answer such foreign and un-
accustomed calls as impulses reaching them along normally efferent
nerves. There is good evidence that muscular excitation is not
carried over to the motor nerve- fibres; in other words, the wave
of action flows from the nerve to the muscle, but cannot be got
to flow backwards. Excitation of the central end of an efferent
(anterior) spinal root is not transferred to the corresponding afferent
(posterior) root, the connection between the efferent and afferent
neurons presenting the character of a physiological ' valve,' which
permits impulses to pass only in one direction. We have seen that
vaso-dilator impulses possibly pass out to the limbs over fibres
which, morphologically speaking, are afferent fibres (p. 181). And
we shall see that a nutritive influence is exerted over the afferent
fibres of the spinal nerves by the ganglion cells of the posterior root
ganglia (p. 796), an influence which must spread along these fibres
in the opposite direction to that of the normal excitation.
The best proofs of double conduction in nerves, with artificial stimu-
lation, are: (i) The propagation of the negative variation or action
current in both directions. This holds for sensory as well as for motor
fibres, as du Bois-Reymond showed on the posterior roots of the spinal
nerves of the frog and the optic nerves of fishes. (2) Stimulation of the
posterior free end of the electrical nerve of Malapterurus (p. 841) causes
discharge of the electric organ, although the nerve-impulse travels nor-
mally in the opposite direction. (3) If the lower end of the frog's
sartorius is split into two, gentle stimulation of one of the tongues causes
contraction of individual fibres in the other. This is supposed to be due
to conduction of the nerve-impulse up a twig of a nerve-fibre distributed
to the one tongue, and down another twig of the same fibre going to the
other tongue. A similar experiment can be done on the gracilis of the
frog. This muscle is divided by a tendinous inscription into two parts,
each supplied by a branch of a nerve which divides after entering the
muscle. Stimulation of either twig is followed by contraction of both
parts of the muscle (Kuhne).
Bert's much-quoted experiment on the rat is valueless as a proof of
double conduction. He caused union of the point of the tail with the
tissues of the back, then divided the tail at the root, and found that
stimulation of what was now the distal end caused pain. From this he
concluded that the sensory fibres of the ' transposed ' tail conducted
in the direction from root to tip. But the conclusion is not warranted,
for sensation disappeared in the tail after the section, and did not
THE NERVE-IMPULSE OR PROPAGATED DISTURBANCE 793
return till some months later, when the nerve-fibres, after degenerating,
would have been replaced by new sensory fibres growing down from
the dorsal nerves (Ranvier). For a similar reason the so-called union
of the peripheral end of the cut hypoglossal nerve (motor) with the
central end of the cut lingual (sensory) proves nothing as to double
conduction, nor as to the possibility of motor nerves taking on a sensory
function. For while sensation is after a time restored in the affected
portion of the tongue, this is due to the growth of sensory fibres from the
central stump of the lingual down through the degenerated hypoglossal,
and not to the conduction upwards of sensory impulses by the motor
fibres of the latter.
Every fibre of a nerve is physiologically isolated from the rest,
so that an impulse set up in a fibre runs its course within it, and
does not pass laterally into others (law of isolated conduction). In
connection with this physiological fact there is the anatomical fact
that nerve- fibres do not normally branch in the trunk of a peripheral
nerve. (But see p. 802.) It has, however, been shown that bifurca-
tion of nerve-fibres may occur in the spinal cord (Sherrington).
The axis-cylinder of a peripheral nerve-fibre only begins to branch
where complete isolation of function is no longer required, as within
a muscle. The experiment of Kuhne on double conduction, men-
tioned above, shows that an excitation set up in one twig or one
fibril of an axis-cylinder which has branched can spread to the rest.
Velocity of the Nerve- Impulse. — We have said that the nerve-
impulse travels with a measurable velocity. It is now time to
describe how this has been ascertained (p, 818). For motor fibres
the simplest method is to stimulate a nerve successively at two
points, one near its muscle, the other as far away from it as possible,
and to record the contractions on a rapidly-moving surface (pendu-
lum or spring myograph) (p. 746). The apparent latent period of
the curve corresponding to the nearer point will be less than that
of the curve corresponding to the point which is more remote, by
the time which the impulse takes to pass between the two points.
The distance between these points being measured, the velocity is
known. Helmholtz found the velocity for frog's nerves at the
ordinary temperature of the air to be a little under, and for human
nerves, cooled so as to approximate to the ordinary temperature,
a little over 30 metres per second. For observations on man the
contraction curves of the flexors of one of the fingers or of the
thumb may be recorded, first with stimulation of the brachial plexus
at the axilla, and then with stimulation of the median or ulnar
nerve at the elbow. Probably at the same temperature there is
little difference in the rate of transmission in the nerves of warm-
blooded and cold-blooded animals, but temperature has a con-
siderable influence (p. 782).
By cooling a frog's nerve Helmholtz reduced the rate to ^ of its value
at the ordinary temperature. In the human arm he found a variation
from 30 to 90 metres per second, according to the temperature, 50 metres
794 NERVE
being about the normal rate. This is greater than the speed of the
fastest train in the world. According to Piper's recent measurements
the velocity in human medullated nerve is even greater than Helmholtz
concluded, about 120 metres a second under ordinary conditions. The
rate is independent of the intensity of the excitation. The velocity
with which the negative variation is propagated (p. 824) is the same as
that of the nerve-impulse.
In sensory nerves there is no reason to believe that the velocity of the
nerve-impulse differs from that in motor nerves, but experiments on
man really free from objection are as yet wanting.
The usual method is to stimulate the skin first at a point distant from
the brain, and then at a much nearer point. The person experimented
on, as soon as he feels the stimulation, makes a signal, say, by closing
or opening with the hand a current connected with an electric time-
marker, writing on a moving surface. There is, of course, a measurable
interval between the excitation and the signal, and this being in general
longer the more remote the point of stimulation is from the brain, it is.
assumed that the excess represents the time taken by the nerve-impulse
to pass over a length of sensory nerve equal to the difference in the
length of the path. But there is this difficulty, that the propagation
of the impulse from the point of stimulation to the brain is only one
link in the chain of events of which the signal marks the end. The
impulse has first to be transformed into a sensation, and then the will
has to be called into action, and an impulse sent down the motor nerves
to the hand. And while the time taken by the excitation in travelling
• up and down the peripheral nerve-fibres is probably fairly constant, the
time spent in the intermediate psychical processes is very variable.
SECTION II. — CHEMISTRY, DEGENERATION, AND REGENERATION OF
NERVE.
Chemistry of Nerve. — Our knowledge of this subject is still scanty;
and most of what we do know has been obtained from analyses,
not of the peripheral nerves, but of the white matter of the central
nervous system
Proteins are present, especially in the axis-cylinder. The proteins of
nervous tissue include two globulins, one coagulated by heat at 47° C.,
the other at 70° to 75° C., and a nucleo -protein coagulating at 56° to
60° C.
Very important constituents are certain substances soluble in organic
solvents, like benzol and ether, and comprising cholesterin, certain
phosphatides (kephalin and lecithin], and certain cerebrins or cerebrosides.
The cerebrins are glucosides containing nitrogen, but no phosphorus,
and they yield a reducing sugar (galactose) on hydrolysis. In the
nervous tissue there is also present, according to some authorities, a
compound called protagon. Others consider it a mere mixture of phos-
phatides and cerebrosides. The lipoids of nerve-fibres belong largely to
the medullary sheath, but they are not confined to it, since non-medul-
lated nerves also yield a considerable quantity of lipoids (11*5 per cent,
of the solids as against 46-6 per cent, for medullated nerves). Non-
medullated nerves (splenic nerves of the ox) are distinguished from
medullated nerves (human sciatic) by the high proportion of their total
lipoids constituted by the phosphatides (kephalin and lecithin) and
cholesterin. Thus, in non-medullated fibres 47 per cent, of the lipoid
CHEMISTRY OF NERVE 795
extract consisted of cholesterin, and 23-7 per cent, of kephalin; while
in the medullated fibres cholesterin made up only 25 per cent, of the
extract, and kephalin 12-4 per cent. On the other hand, the cere-
brosides are present, both relatively and absolutely, in much larger
quantity in medullated than in non-medullated nerves. In both
varieties of fibres kephalin, and not lecithin, is the chief phosphorus-
containing body (Falk). The medullary sheath further contains a
kind of network of a peculiar resistant substance, neurokeratin. The
neurilemma consists of substances insoluble in dilute sodium hydroxide.
Gelatin is obtained from the connective tissue which binds the nerve-
fibres together. There may also be ordinary fat in the meshes of the
epineurium connecting the bundles. Small quantities of xanthin,
hypoxanthin, and other extractives, can also be obtained from nerve.
According to Halliburton's analyses, the water in sciatic nerves amounts
to 65*1 per cent., and the solids to 34-9 per cent. The proteins make up
29 per cent, of the solids.
For an analysis of the white matter of the brain, see Chapter XVI.
Nerve-cells contain no potassium, according to Macallum; and this
is true both of the dendrites and the axons. In medullated nerves, how-
ever, potassium compounds are present external to the axons, chiefly at
the nodes of Ranvier (Frontispiece) and in the neurokeratin framework
of the sheath.
The only chemical difference between living and dead nervous tissue
which has been made out with any degree of certainty is that the former
is neutral or faintly alkaline, and the latter acid, in reaction to such
indicators as litmus. This is especially true of the grey matter of the
central nervous system, although the white matter also is often found
acid. The change of reaction is due to the accumulation of lactic acid.
Such a change has not hitherto been clearly demonstrated in peripheral
nerves, either after death or after prolonged stimulation. The (non-
medullated) splenic nerves of the dog, even after stimulation for six
hours, never became acid (Halliburton and Brodie).
Degeneration of Nerve. — Nerve-fibres are ' bound in the bundle
of life ' with the nerve-cells from which their axis-cylinders arise;
the connection between cell and axon once severed, the nerve-
fibre dies inevitably. This is an illustration of a general law that
no portion of a cell can live once it is separated from the nucleus.
We shall see later on that changes also occur in the nerve-cell whose
axon has been divided from it, although they are of a different
nature (rather a slow atrophy than an acute degeneration), and
do not necessarily lead to the destruction of the cell. We must
regard the neuron not only as a morphological unit, a single cell
from nucleus to remotest end-brush, but also as a functional and
nutritive unit, the fortune of any portion of which is not in-
different to the rest. Thus, when a man's arm is amputated the
arm fares worse than the man, for the arm dies. But the man is
not unaffected. He lives, but he suffers much temporary disturb-
ance and some permanent loss. What is left of him is not quite
the same as it was. The acute changes that occur in severed nerve-
fibres are most conveniently studied in the peripheral nerves,
although essentially similar phenomena take place also in the fibres
of the central nervous system.
796
NERVE
A spinal nerve is composed of efferent fibres whose cells of origin
are in the grey matter of the anterior horn, and afferent fibres
whose cells of origin are in the posterior root ganglion. When such
a nerve is cut below the junction of its roots, muscular paralysis
and impairment of sensation at once follow in the region supplied
by the nerve; but for a time the nerve remains excitable to direct
stimulation. The excitability
gradually diminishes, and in a
few days is completely gone.
If portions of the nerve distal
to the lesion are examined at
different periods after section, a
remarkable process of degenera-
tion (commonly spoken of as
Wallerian degeneration) is seen
to be going on. In the medul-
lated fibres this begins on the
second or third day with a
swelling of the axis-cylinder,
which breaks up into detached
pieces (fragmentation), and as-
sumes a granular appearance.
The medullary sheath also under-
goes fragmentation at the lines
of Lantermann, and a little later
separates into clumps and drop-
lets of myelin. The nuclei under
the neurilemma increase in size,
proliferate by mitosis, and in-
sinuate themselves between the
fragments of the medullary
sheath and axis-cylinder, which
ultimately disappear, leaving the
nerve- fibre represented only by a
kind of mummy of connective
tissue, in which the neurilemma
with its abnormally numerous
Fig. 277. — Degeneration of Nerve-Fibres
after Section (Barker, after Thoma).
I, normal fibre; II, degenerating fibre;
III, further stage of degeneration;
S, neurilemma ; m, medullary sheath;
A, axis-cylinder; L, Lantermann's line
or cleft; R, node; mt, drops of myelin;
a, remains of axis-cylinder ; w, prolifera-
ting cells of neurilemma.
nuclei can still be recognized.
The fragmentation of the myelin
sheath is not dependent upon the proliferation of the nuclei, since it
occurs also in nerves removed from the body and kept under con-
ditions in which the nuclei do not proliferate (Feiss and Cramer).
The protoplasm around the nuclei of the neurilemma also increases in
amount, and undergoes other changes, which will be more particularly
referred to in describing the regeneration of nerve. The degenerative
process begins near the cut end, and extends gradually to the peri-
DEGENERATION OF NERVE
797
phery, and more rapidly in warm- than in cold-blooded animals. At
any rate, that is the interpretation generally given to the fact that at
a given period after section the changes — especially the breaking-
up of the myelin — are more pronounced near the proximal end of
the peripheral stump. In a mammal degeneration is far advanced
in a fortnight, although the last remnants of the myelin may not
be absorbed for months. In the degenerated nerve (cat's sciatic)
the percentage of phosphorus undergoes a diminution from about
the third day. About the eighth day the loss of phosphorus — i.e.,
of the phosphatides (lecithin, kephalin) — is markedly accelerated,
coinciding with the appearance of a strong Marchi* staining re-
action. By the twenty-ninth day the degenerated nerve is prac-
tically devoid of phosphorus. A progressive increase in the water
and a diminution in the total
solids also culminate about the
same time (Mott and Halli-
burton). In the portion of the
nerve-fibre still connected with
the nerve-cell the degeneration
only extends as far back as the
next node of Ranvier, and seems
to be due to the direct effect of
the injury. In non-medullated
fibres, such as the fibres arising
from the cells of the superior
cervical ganglion (Tuckett), the
degeneration is confined to the
axis-cylinders. It begins in
about twenty-four hours after section, and the loss of excitability
and conductivity is complete by the fortieth hour.
It follows from what has been said as to the position of the cells
of origin of the root fibres of the spinal nerves that section of
the anterior root causes degeneration on the peripheral, but not on
the central side of the lesion, f Only the anterior root fibres in the
mixed nerve degenerate. Section of the posterior root above the
ganglion causes degeneration of the central stump, but not of
the portion still connected with the ganglion, nor of the posterior
root fibres below the ganglion or in the mixed nerve. Section of
the posterior root below the ganglion causes degeneration of the
fibres of the root below the section and in the mixed nerve, but not
above it.
* The chief constituents of Marchi's solution are potassium bichromate and
osmic acid. It stains medullated nerve-fibres black in the earlier stages of
degeneration.
| A few fibres in the peripheral stump of the anterior root do not degenerate,
and a few fibres in the central stump do. These are the 'recurrent fibres,'
whose course is described on p. 892.
Fig. 278. — Degeneration of Spinal Nerves
and their Roots after Section. The
shading shows the degenerated portions.
798 NERVE
Regeneration of Nerve. — Degeneration of nerve is followed, if
its divided ends are not kept artificially apart, by a process of re-
generation, already distinct under favourable conditions in from
three to four weeks after the section, and indeed in some cases
commencing as early as the second week. This consists in the
outgrowth of new axis-cylinders, in the form of fine fibres, from
the ends of the divided axis-cylinders of the central stump of the
nerve. These push their way into and along the degenerated
fibres, ultimately acquire a medullary sheath, and develop into
complete nerve-fibres, restoring first sensation, and later 'on volun-
tary motion, to the paralyzed part. The process needs several
months for its completion, even in warm-blooded animals. It
takes place under the influence of the nucleated portion of the
neuron (the cell-body), and is never completed if the peripheral
and central portions of the nerve are permanently separated by a
substance through which the new axis-cylinders cannot grow or
by a gap too wide for them to bridge over. When the 'cut ends of
the nerve are carefully sutured together, the conditions for com-
plete and speedy regeneration are rendered more favourable — a
fact which finds its application in the surgical treatment of injured
nerves. The cycle of chemical changes described in the degenerating
nerve is retraced in the reverse order. In the cat's sciatic the
first sign of the return of the phosphorus was seen with the beginning
of the normal myelin reaction about the sixtieth day after section.
At the one-hundredth day the phosphorus content was almost as
great as that of the normal nerve (a little under i per cent, of the
solids for the regenerated, as compared with a little over i per cent,
for the normal nerve).
It is not as yet well understood how the regenerating fibres are
directed in their growth, so that they join their centres to the appro-
priate end-organs without mistake. That they have a high capacity
for finding their way is indicated by the results of cross-suturing
such nerves as the median and ulnar — i.e., of uniting the central end
of the one with the peripheral end of the other. Howell and Huber
found that after this operation in the dog, both co-ordinated volun-
tary motion and sensation returned in large measure in the parts
supplied by the nerves. Here the motor fibres of the median nerve
must, of course, have made connection with muscles previously
supplied by the ulnar, being guided to them along the nerve-sheaths
of the latter. Doubtless the old nerve-sheaths serve to some
extent as mechanical guides by offering to the new axons a path of
least resistance. And when a nerve-trunk containing motor and
sensory fibres is simply crushed so as to destroy all physiological
continuity, but is not cut, no distortion of the motor and sensory
' patterns ' of the nerve — in other words, no ' straying ' of the fibres
from their old paths — can be detected on regeneration. When the
REGENERATION OF NERVE
799
nerve is cut and then sutured, a certain amount of distortion of the
pattern is inevitable. The mechanical apposition of central and
peripheral stumps is, of course, much more nearly perfect in the
crushed nerve than in the cut nerve, however exact the suturing
may be (Osborne and
Kilvington). Yet, even
after crushing or liga-
tion of nerves, or after
section and suturing,
the regenerating fibres
do not pass straight
through the scar tissue
from the central to the
peripheral stump, but
cross and mingle, ap-
parently in the most
inextricable confusion
(Feiss) (Fig. 279). This
is due to the prolifera-
tion of cells in the scar
which run in all direc-
tions, and show no
signs of following the
Fig. 279. — Regenerating Fibres crossing in the Scar
after Ligation of a Dog's Sciatic Nerve 165 Days
previously. Weigert-Pal stain. Drawn under oil-
immersion (Feiss).
parallel arrangement of the nerve-sheaths in the central or the
distal segment. These being formed before the regenerating
nerve- fibres, the latter must necessarily grow also in all direc-
\Sk±.fyMt*\ tions in the scar.
J^A This, however, is a
,NeUro«vo.i ~*-,'''^.-%r*' '• local phenomenon.
Beyond the scar the
, 4~^;-->--,r_ «:_ .-'/• arrangement of the
IPJ \ ,.y regenerating axis-
',/ cylinders recovers
^ its regularity, and
H^^ the amount of dis-
tortion of the nerve
pattern, as indicated
by histological ex-
amination and
functional tests, is
by no means so
great as the com-
plete effacement of the pattern in the scar might appear to promise.
That the degenerated peripheral stump directs the growth of
the axons from the central stump in some other than a merely
mechanical way is evident from the experiments of Langley on
Ext.
Fig. 280. — Semidiagrammatic Representation of Longi-
tudinal Section through Neuroma or Scar produced by
ligating the Sciatic Nerve with Catgut, and crushing it
with a hasmostat just above its Division into the Ex-
ternal and Internal Popliteal Nerves. Weigert-Pal
preparation (Feiss).
8oo NERVE
regeneration of the cervical sympathetic in the cat after section
below the superior cervical ganglion. The nerve contains fibres
of various functions which reach it from the upper thoracic nerves.
The anterior roots of the first and third thoracic nerves supply the
cervical sympathetic mainly with fibres which end in the ganglion
around cells that give off dilator fibres for the pupil. The fibres
connected with the cells in the ganglion which send vaso-motor
fibres to the vessels of the ear are for the most part contained in
the anterior roots of the second and fifth thoracic nerves; and the
fibres connected with the cells that give origin to the pilo-motor
fibres for the hairs of the face and neck in the anterior roots of the
fourth to the seventh. Stimulation of any one of the upper thoracic
roots accordingly causes a specific effect, which, according to
Langley, is in general the same after regeneration as before section
of the cervical sympathetic. We must assume, therefore, that each
regenerating fibre seeks out either the ganglion cell with which it
was originally connected, or one belonging to the same class. No
mere mechanical guidance of the growing axons by the old neuri-
lemmas will suffice to explain this selective growth. It is necessary
to postulate, in addition, an attraction of a chemical or physico-
chemical nature (chemiotaxis), dependent upon a specific relation
between the new axons and the scaffolding of the peripheral stump
or the ganglion cells. But it is not possible at present to form any
very precise conception of the properties on which the chemiotactic
phenomena depend. And the specificity is not an absolute one.
Under certain conditions these pre-ganglionic nerve-fibres (that is
to say, nerve-fibres running from the spinal cord to end around the
sympathetic ganglion cells) can form connections with nerve-cells
of a different class — e.g., pupillo-dilators with cells whose axons
end in the erector muscles of the hairs. Further, after section of
the sympathetic above the superior cervical ganglion, the post-
ganglionic nerve-fibres (i.e., the fibres coming off from the cells of
the ganglion) may also, if the opportunity be favourable during
regeneration, exchange their old end-organs for new ones ; pilo-
motor fibres, for instance, finding their way into the iris and becoming
pupillo-dilators. After excision of the superior cervical ganglion,
the cervical sympathetic does not recover its function. Accordingly
the pre-ganglionic fibres cannot form direct functional connection
with the post-ganglionic fibres, but can become connected with
them only indirectly through the ganglion cells: Nor can efferent
post-ganglionic fibres achieve regenerative union with a cerebro-
spinal (somatic) motor nerve, although they can themselves re-
generate, as has been shown, e.g., in the case of the vaso-constrictors
of the limbs. On the other hand, union easily takes place between
pre-ganglionic fibres and efferent somatic fibres, and vice versa.
For example, the cervical sympathetic can unite with the phrenic
8oi
nerve, and cause contraction of the diaphragm, or with the recurrent
laryngeal nerve, and cause movement of the vocal cords, or with
the spinal accessory, and cause contraction of the sterno-mastoid
muscle. Conversely, the phrenic nerve, when united with the cer-
vical sympathetic, can, when stimulated, produce the usual effects
observed on exciting the latter nerve (Langley and Anderson).
Central and Autogenetic Theories of Regeneration. — Although
the establishment of connection with the central end of the
cut nerve is necessary for complete regeneration, it must not
be supposed that no share whatever is taken in the process by
the peripheral stump. Even while it remains completely isolated
from the central nervous system, changes occur which are often
described as the third or final stage of degeneration, but which are
more correctly interpreted as forming a stage in the regenerative
.cycle. Spindle-shaped cells or fibres with elongated nuclei make
their appearance, produced by the proliferation of the nuclei of the
primitive sheath already described, and the increase of the proto-
plasm in which these nuclei are embedded. These so-called axial
strand fibres or this fibrillated protoplasm may appear long before
the remains of the degenerated axis-cylinder and myelin sheath
have been completely removed. It is generally acknowledged that
in the adult they do not develop beyond this, so long as the peri-
pheral portion of the nerve remains completely isolated, but neither
do they disappear even after a very long interval. When strict
precautions against union with other nerve-trunks were taken, the
radial nerve of an adult cat was found in this resting-stage nearly
a year and a half after division, and the same was true after two
years and a half in a nerve divided in a human being. The fibres
are incapable of being excited or of conducting nerve impulses.
The precise relation between these axial strand fibres of the peri-
pheral stump and the myelinated fibres found there after regenera-
tion has been much debated. All are agreed that nerve-fibrils
sprout from the central stump, and the weight of evidence is in
favour of the long-accepted view that it is by the growth of these
fibrils along the peripheral stump that the new axons are formed,
and that all the changes in the distal portion of the nerve, however
important for directing and perhaps sustaining the growth of the
central fibrils, are subsidiary to this. But some maintain that the
outgrowing central fibrils meet and unite with corresponding fibrils
sprouting from the peripheral stump, and that the new axis-
cylinders arise from the fibrils of the axial strand. It is said that
very shortly after being brought into connection with the central
portion of the same or of another nerve by careful suturing the
spindle cells begin to lengthen, and form non-medullated fibres,
like those of the sympathetic. Four weeks after union the afferent
fibres, although still non-medullated, are capable of being stimulated
51
802 NERVE
mechanically and electrically, and of conducting impulses towards
the centre. In about eight weeks they become medullated, but at
first are of small calibre (Head and Ham) . Bethe, the most strenuous
defender of the inherent regenerative power of the isolated peri-
pheral stump (autogenetic theory), has even stated that complete
regeneration occurs in young animals in nerves entirely separated
from their centres. There is no doubt that this result is due to
some error of technique or of interpretation. The controversy
turns largely upon the precautions judged necessary to prevent the
ingrowth of central fibres. And while it is comparatively easy to
make sure, by removing a large part of it, that the central end of
the nerve under observation shall remain completely unconnected
with the peripheral end, it is often a matter of the greatest difficulty
to prevent the union of the distal stump with central fibres from
other sources — e.g., from the nerves cut in the wound. Many of the
results which seemed to favour the autogenetic theory were cer-
tainly due to this cause.
The most conclusive evidence in favour of central and against
autogenetic regeneration, because the most direct and uncompli-
cated, has been afforded by the demonstration that the development
of axis-cylinders occurs in vitro in a suitable plasmatic medium, in
the absence of any other elements than the nerve-cells from which
they arise (Harrison). This observer, working with the medullary
plates of tadpoles, in which the nerve-cells originate in the embryo,
showed further that peripheral nerves do not develop when the
nerve-centres are removed, and that the sheath-cells of Schwann are
not essential to the growth of axis-cylinders, since in their absence
the latter continue to grow and reach their normal length. It has
also been proved that nerve-fibres grow out from pieces of the cere-
bellum and spinal ganglia (Fig. 281) of young mammals when cul-
tivated on clotted plasma outside of the body (Fig. 337, p. 857).
Many fibres sprouting out from the spinal ganglia attain a length of
more than half a millimetre in forty-eight hours, and their growth
need not be accompanied by either neuroglia or connective tissue.
When portions of normal peripheral nerve are incubated in plasma
no growth of axis cylinders -is ever observed, nor does the Wallerian
degeneration occurring in peripheral nerves incubated in Ringer's
solution take place (F;g. 282). On the other hand, if nerves in which
Wallerian degeneration has been produced by section are placed in
plasma on the fifth day after section or later, growth of the elements
of the sheath of Schwann may be seen, again unaccompanied by any
growth of axis cylinders (Ingebrigtsen).
A fact of great physiological interest, and also of practical impor-
tance, in connection with the anastomosis of nerves for the relief of
certain forms of paralysis, is the bifurcation of axons in regeneration,
when the conditions are such that the axons of the central stump are
offered more than one path along which to regenerate. If, for instance,
a limb nerve-trunk containing motor fibres is cut, and its central end
REGENERATION OF NERVE
803
sutured both to its own distal end and to the distal end of an adjacent
nerve-trunk, the sum of the nerve-fibres in the two distal trunks after
regeneration has occurred is greater than the number of fibres in the
central stump (Kilvington). That this is due to splitting of axons is
Fig. 281. — Two-day-old Culture of Spinal Ganglia of a Guinea Pig Six Days Old
(Ingebrigtsen).
Fig. 282- — Microphotograph of Nerve Fibres from the Sciatic Nerve of a Rabbit,
incubated in Plasma for Twelve Days. Hardened in formalin and stained
with hasmatoxylin. No trace of Wallerian degeneration (Ingebrigtsen).
shown by the fact that an axon reflex (p. 913) can be elicited on dividing
one of the distal trunks and stimulating its central end after complete
separation of the proximal or parent stem from the central nervous
system. Even when the second path offered to the regenerating motor
axon is a sensory path, bifurcation of the axon occurs, one branch
8o4 NERVE
passing down along the previous motor path to its proper muscular
termination, and the other passing down the sensory path. Although
there is no evidence that efferent fibres can unite with afferent fibres, a
degenerated afferent path can therefore serve as a chemiotactic scaffold-
ing or guide for the growth of regenerating motor axons, though not
such an efficient one as a degenerated motor path. Sensory fibres,
however, cannot regenerate along motor paths or make functional union
with the receptive substance of skeletal muscle.
Regeneration of the fibres of the central nervous system either does not
in general occur, or is exceedingly difficult to realize. This lends support
to the doctrine of the importance of the neurilemma in regeneration,
since its elements are scantily developed in the fibres of the brain and
cord (p. 860) . Regeneration of the fibres which proceed from the cells of
the spinal ganglia along the posterior roots into the cord may take place
after the roots have been cut, so that the normal reflexes through the res-
piratory, cardiac, and vaso-motor centres may be once more obtained.
Degeneration of Muscle. — Experimental section or, in man,
traumatic division or compression of a nerve leads not only to its
degeneration, but ultimately, if regeneration of the nerve does not
take place, to degeneration of the muscles supplied by it as well.
The muscle- fibres dwindle to a quarter of their normal diameter;
the stripes disappear; the longitudinal fibrillation fades out; and at
length only hyaline moulds of the fibres are left, filled, and separated
by fatty granules and globules and surrounded by engorged capil-
laries. Amidst the general decay, the muscular fibres of the
terminal ' spindles ' with which the afferent nerves of muscles arc
connected alone remain unchanged (Sherrington). Certain dis-
eases of the cord which interfere with the cells of the anterior horn
cause degeneration of motor nerves, and ultimately of muscles.
The motor nerve-endings degenerate sooner than the sensory.
Both may, under suitable conditions, regenerate (Huber).
Reaction of Degeneration. — Muscles whose motor nerves have been
separated from their trophic centres show, when a certain stage in
degeneration has been reached, a peculiar behaviour to electrical
stimulation, called the ' reaction of degeneration.' To the constant
current the muscles are more excitable, and the contraction slower and
more prolonged than normal. When a current, either constant or
induced, is passed through a normal muscle, the muscular fibres may be
stimulated either directly, or indirectly through the intramuscular
nerves. Under ordinary conditions the nerves respond more readily
than the muscular fibres, especially to momentary stimuli like induction
shocks, and therefore the so-called direct stimulation of uncurarized
muscle is as a rule an indirect stimulation. When the muscle is
curarized and the nerves thus eliminated, the excitability to induced
currents is found to be diminished. The same is the case in a muscle
which exhibits the reaction of degeneration after section of its motor
nerve, only the loss of excitability to induced currents is greater, and
may even be complete. The common statement that the closing anodic
contraction is stronger than the closing kathodic — the opposite of the
ordinary law — is subject to so many exceptions that it has no diagnostic
value. The nerves are inexcitable either to constant or induced
currents. The reaction of degeneration is only obtained from paralyzed
muscles when the paralyzing lesion is situated in the cells of the anterior
TROPHIC NERVES 805
horn irom which the motor nerves take origin, or below that level.
Accordingly, it is sometimes of use in localizing the position of a lesion.
For instance, a group of muscles might be paralyzed by a lesion in the
grey matter of the brain or in the nerve-fibres connecting this with the
grey matter of the anterior horn of the cord, or in the grey matter of
the anterior horn itself, or in the peripheral nerve-fibres leading from
this to the muscles. In the first two cases the reaction of degeneration
would be absent, although the muscles, if the lesion was of long standing,
would be atrophied to some extent; in the last two there would be acute
atrophy of the muscles, and the reaction of degeneration would be
obtained.
Trophic Nerves. — There is no question that nerves exert a very
important influence upon the nutrition of the parts supplied by
them, in influencing the specific function of those parts. So that
in this sense all nerves are trophic nerves. The fact that the proper
nutrition of nerve-fibres and striated muscular fibres is dependent
on their connection with nerve-cells has been by some writers
generalized into the doctrine that all tissues are provided with
' trophic ' nerves, which, apart from any influence of functional
activity, regulate the nutrition of the organs they supply. But the
evidence for this view, when weighed in the balance, is found
wanting; and it may be said that up to the present no unequivocal
proof, experimental or clinical, has ever been given of the existence of
specific trophic fibres, anatomically distinct from other efferent or
afferent nerves.
It is true that in various diseases and injuries of the nervous system
nutritive changes in the skin, and sometimes in the bones and joints,
are apt to appear. But it is very difficult in such cases to disentangle
the effects produced by accidental injuries acting on structures whose
normal sensibility is lost or lessened, or whose circulation is deranged,
from true trophic changes. The most that can be said is that there is
some evidence that the power of the skin to resist injury, and the
capacity of recovering from it, are diminished by interference with its
nerve-supply, so that a large sore may result from a trifling lesion, and
healing may be slow and difficult. Experimentally it has been found
that division of the trigeminus nerve within the skull is sometimes
followed by cloudiness of the cornea, going on to ulceration, and ulti-
mately inflammation and destruction of the eyeball. Ulcers also form
on the lips and on the mucous membrane of the mouth and gums ; and
the nasal mucous membrane on the side corresponding to the divided
nerve becomes inflamed. But in this case the sensibility of the eye is
lost, and reflex closure of the eyelids ceases to prevent the entrance of
foreign bodies. The animal is no longer aware of the contact of particles
of dust or bits of straw or accumulated secretion with the conjunctiva,
and makes no effort to remove them. The lips, being also without
sensation, are hurt by the teeth, particularly as the muscles of mastica-
tion on the side of the divided nerve are paralyzed, and decomposed
food, collecting in the mouth, and inhaled dust in the nose, will tend
still further to irritate the mucous membranes. There is thus no more
need to assume the loss of unknown trophic influences in order to
explain the occurrence of the ulcerative changes than there is to
explain the production of ordinary bed-sores, bunions or corns on parts
peculiarly liable to pressure. And, as a matter of fact, if the eye be
8o6 NERVE
artificially protected, after section of the trigeminal nerve, the
ophthalmia either does not occur or is much delayed.
In man, too, a case has been recorded in which both the fifth and
the third nerves were paralyzed. The eye was still shielded by the
contraction of the orbicularis oculi supplied by che seventh nerve, as
well as by the drooping of the upper eyelid that accompanies paralysis
of the third. It remained perfectly sound for many months, till at
length the tumour at the base of the brain which had affected the other
nerves involved the seventh too. The eye was now no longer com-
pletely closed; inflammation came on, and vision was soon permanently
lost (Shaw). In another case a patient lived for seven years with
complete paralysis of the fifth nerve, yet the eye remained free from
disease and sight was unimpaired (Cowers).
The so-called ' trophic ' effects following division of both vagi we
have already discussed (p. 286) so far as they are concerned with the
respiratory system. The degenerative changes sometimes seen in the
heart are perhaps due to its being overworked in the absence of nervous
restraint on its functional activity. The nutritive alterations in
muscles and salivary glands after section of motor and secretory nerves
seem to depend in part on functional and vaso-motor changes. In the
paralyzed muscles nutrition is not only interfered with in consequence
of their inactivity, as would be the case even if the paralysis were due
to a lesion above the level of the anterior cornual cells, but the already
poorly nourished fibres are continually pressed upon by the capillaries,
which are dilated owing to the division of the vaso-motor nerves. The
degeneration may also be in part ascribed to the loss of a reflex tonic
influence exerted on the muscles by the spinal cord, through the
ordinary motor nerves (p. 917). When all allowance has been made for
these factors, the rapid and characteristic degeneration of the striated
muscles, after their connection with the central nervous system is
severed, is still inexplicable, except on the assumption that their
nutrition is specially related to the integrity of their efferent nerves.
In other words, it is necessary to suppose, not, indeed, that distinct
trophic nerves exist for the muscles, but that an influence or impulses,
which can be termed trophic or nutritive, do normally pass out to them
from the spinal cord along their motor nerves.
Section of the cervical sympathetic in young rabbits and dogs increases
the growth of the ear and of the hair on the same side. But it is
impossible to separate these consequences from the vaso-motor paral-
ysis; and the same is true of the hypertrophy following section of the
vaso-motor nerves of the cock's comb and of the nerves of the bones.
After section of the superior laryngeal the vocal cord on the side of the
section is at once rendered motionless, and remains so, but the muscles,
notwithstanding their inaction, do not degenerate. And Mott and
Sherrington have found that, although section of the posterior roots in
monkeys is followed after a time (three weeks to three months) by
ulceration over certain portions of the foot, no corresponding lesions
occur in the hand. They believe, therefore, that the lesions are not due
to the withdrawal of a reflex trophic tone, but are accidental injuries
in positions specially exposed to mechanical or microbic insults.
One of the best examples of interference with the proper nutrition of
a part produced by a lesion in the nerves supplying it is an eruption
(herpes zoster), limited to the skin supplied by the nerve-fibres coming
from one or more spinal ganglia, and depending on an (infectious)
inflammatory change in the ganglia. It has been suggested that the
vesicles are formed either because the passage of afferent impulses
normally concerned in the nutrition of the skin is interfered with or
CLASSIFICATION OF NERVES
807
because the skin is bombarded by antidromic (p. 181) impulses dis-
charged from the inflamed ganglia. But an alternative hypothesis is
that a toxine spreads out along the nerves from the ganglia, just as
in traumatic tetanus the toxine is known to pass in the opposite direc-
tion along the nerves from the seat of injury to the central nervous
system.
Classification of Nerves. — Omitting the group of ' trophic ' nerves,
and the even more problematical' thermogenic ' fibres (which some
have supposed to preside over the production of heat, and therefore
to assist in the regulation of the temperature of the body, but of
whose existence as distinct and specific nerve-fibres with no other
function there is not the slightest proof), peripheral nerves may be
classified as follows:
Centripetal
or afferent
fibres.
' Smellv
Taste.
Hearing.
Sight.
Touch (light touch).
Pressure (perhaps in-
cluding the nerves oi
muscular sense).
Warmth— Cold.
Pain.
Calibre of small arteries
(pressor, depressor).
Action of heart.
Respiratory movements.
Visceral movements.
Glandular secretion.
Ordinary skeletal
muscles.
Skeletal muscles
Visceral , ,
Vascular / Vaso -constrictor
vdocuidr .. i f^ * . .
I Cardio-augmentor.
Erector muscles of hairs (pilo-motor
fibres).
( Visceral muscles
2. Inhibitory nerves for \ ( Vaso-dilator.
I Vascular ,, \ Cardio-inhibi-
3. Secretory nerves [ tory.
* It is not known whether the afferent portion of a reflex arc is always com-
posed of fibres included in the first two categories, although undoubtedly in
some cases it is.
Centrifugal
or efferent
fibres.
I. Nerves of special sensation
2. Nerves of general sensation
3.* Possibly nerves other than
those included under i
and 2, concerned in
reflex changes in
i. Motor nerves for
PRACTICAL EXERCISES ON CHAPTERS XIII. AND XIV.
i. Difference of Make and Break Shocks from an Induction Machine.
— Connect a Daniell or other cell B (p. 724) with the two upper binding-
screws of the primary coil P, and interpose a spring key K in the circuit.
Connect a pair of electrodes with the binding-screws of the secondary
coil (Fig. 283).
8o8
MUSCLE AND NERVE
Electrodes can be very simply made by pushing copper wires through
two glass tubes, filling the ends of the tubes with sealing-wax, and
binding them together with waxed thread. The projecting points may
be filed, and the nerve laid directly on them, or they may be tipped with
small pieces of platinum wire soldered on.
(a) Push the secondary away from the primary, until no shock can
be felt on the tongue when the current from the battery is made or
broken with the key. Then bring the secondary gradually up towards
the primary, testing at every new position whether the shock is per-
ceptible. It will be felt first at break. If the secondary is pushed still
further up, a shock will be felt both at make and at break. From this
we learn that for sensory nerves the break shock is stronger than the
make. The same can easily be demonstrated for motor nerves and
for muscle.
(6) Smoke a drum and arrange a myograph, as shown in Fig. 287.
But omit the brass piece F, and do not connect the primary through
the drum, as there shown, but connect it as in Fig. 283. Pith a frog
(brain and cord), and make a muscle-nerve preparation.
To make a Muscle-Nerve Preparation. — Hold the frog by the hind legs
back upwards; the front part of the body will hang down, making an
angle with the posterior
portion. With strong
scissors divide the back-
bone anterior to this
angle, and cut away all
the front portion of the
body, which will fall
down of its own weight.
Make a circular incision
at the level of the tendo
Achillis, and another at
the lower end of the
femur, through the skin.
The sciatic nerve must
now be dissected out, as
follows : Remove the
skin from the thigh, and,
holding the leg in the
Fig. 283. — Arrangement of Coil for Single Shocks.
left hand, slit up the fascia which connects the external and internal
groups of muscles on the back of the thigh. Complete the separa-
tion with the two thumbs. Cut through the iliac bone, taking
care that the blade of the scissors is well pressed against the bone,
otherwise there is danger of severing the sciatic plexus. Now divide
in the middle line the part of the spinal column which remains above
the urostyle. A piece of bone is thus obtained by means of which the
nerve can be manipulated without injury. Seize this piece of bone with
the forceps, and carefully free the sciatic plexus and nerve from their
attachments right down to the gastrocnemius muscle, taking care not
to drag upon the nerve. The muscles of the thigh will contract, as the
branches going to them are cut. This is an instance of mechanical
stimulation. Now pass a thread under the tendo Achillis, tie it, and
divide the tendon below it. Strip up the tube of skin that covers the
gastrocnemius, as if the finger of a glove were being taken off. Tear
through the loose connective tissue between the muscle and the bones
of the leg, and divide the latter with scissors just below the knee. Cut
across the thigh at its middle.
Fix the preparation on the cork plate of the myograph by a pin passed
PRACTICAL EXERCISES
809
through the cartilaginous lower end of the femur, and attach the
thread to the upright arm of the lever by one of the holes in it. Hang
not far from the axis by means of a hook a small leaden weight (5 to
10 grammes) on the arm of the lever which carries the writing-point,
and move the myograph plate or the muscle-nerve preparation until
this arm is just horizontal. Fasten the electrodes from the secondary
coil on the cork plate with an indiarubber band ; lay the nerve on them ;
and cover both muscle and nerve with an arch of blotting-paper
moistened with physiological salt solution, taking care that the blotting-
paper does not touch the thread. Or put the preparation in a moist
chamber* (Fig. 322, p. 843). Muscle troughs of various kinds may also
Fig. 284. — Lucas's Muscle Trough. A, trough made of hard rubbsr; B, a hard rubber
boss with a hole drilled in it to receive the pin which fastens the gastrocnemius
preparation; H, H, electrodes cased in hard rubber except at the ends, which
in the trough carry platinum wires; C, a brass plate mounted on one side of the
trough, carrying a lever with a vertical arm F ending in a hook, which is attached
by a loop of thread to the tendon of the preparation; G, the writing arm of the
lever; K, M, holes in G for loading the muscle. C can be slid horizontally by
means of the slots in it, and clamped by the screw E. I, tube for running off
the solution.
be used, which permit immersion of a muscle (or nerve) in Ringer's
solution. A convenient form is shown in Fig, 284, but a trough suffi-
cient for the purposes of the student can be easily improvised in any
laboratory. Adjust the writing-point to the drum. Begin with such
a distance between the coils that a break contraction is just obtained
on opening the key in the primary circuit, but no make contraction.
The lever will trace a vertical line on the stationary P- 748. shows a series of curves obtained in this way.
7. Influence of Load on the Muscle- Curve. — Arrange everything as
in 6. Take a tracing first with the lever alone, then with a weight oi
10 grammes, then with 50, 100, 200, and 500 grammes (Fig. 254, p. 748).
8. Influence of Fatigue on the Muscle-Curve. — Arrange as in 7, but
leave on the same weight (say 10 grammes) all the time. Place the
nerve on the electrodes. Leave the short-circuiting key open. The
nerve will be stimulated at each revolution of the drum, and the writing-
point will trace a series of curves, which become lower, and especially
longer, as the preparation is fatigued. Two or four curves can be
taken at the same time, if both ends of one or of two brass slips be
arranged so as to make contact with the projecting wire at an interval
of a semicircumference or quadrant of the drum (Fig. 287). (For
specimen curve, see Fig. 288, p. 814.)
9. Seat of Exhaustion in Fatigue of the Muscle-Nerve Preparation for
Indirect Stimulation. — When the nerve of a muscle-nerve preparation
has been stimulated until contraction no longer occurs, the muscle can,
under ordinary conditions, be made to contract by direct stimulation.
The seat of exhaustion is, therefore, not the general contractile sub-
stance of the muscular fibres themselves. To determine whether it is
the nerve-fibres or some structure or substance intermediate between
them and the ordinary contractile substance of the muscle, perform
the following experiments :
(a) Pith a frog; make two muscle-nerve preparations; arrange them
both on a myograph plate, which has two levers connected with it.
Attach each of the muscles to a lever in the usual way, and lay both
nerves side by side on the same pair of electrodes. Cover with moist
blotting-paper. The electrodes are connected with the secondary of an
induction machine arranged for tetanus. With a camel's hair brush
3i4
MUSCLE AND NERVE
moisten one of the nerves between the electrodes and the muscle with a
mixture ol equal parts of ether and alcohol, diluted with twice its volume
of water, to abolish the conductivity. Or put the mixture in a small
bottle, in which dips a piece of filter-paper. The projecting end of the
filter-paper is pointed, and the nerve is laid on the point. As soon as
it is possible to stimulate the nerves without obtaining contraction in
this muscle, proceed to tetanize both nerves till the contracting muscle
is exhausted. If the other muscle begins to twitch during the stimu-
lation, more of the ether mixture must be painted on the nerve. As
soon as the stimulation ceases to cause contraction in the non-etherized
preparation, wash off the mixture from the other nerve with physio-
logical salt solution, and soon contraction may be seen to take place in
Fig. 288. — Fatigue Curve of Skeletal Muscle: Gastrocnemius of Frog. Indirect
stimulation; taken with arrangement shown in Fig. 287 (p. 812). Time-tracing,
J-JT of a second.
the muscle of this preparation. This shows that the nerve-trunk is still
excitable. Now, both nerves have been equally stimulated, and there-
fore the exhaustion in the non-etherized preparation was not due to
fatigue of the nerve-fibres, but of something between them and the
contractile substance of the muscle.
10. Influence of Veratrine on Muscular Contraction. — Arrange a
drum as in Fig. 287. Pith a frog (brain only), expose the sciatic nerve
in one thigh, and isolate it for \ inch from the surrounding tissues.
Pass under it a strong thread, and ligature everything except the nerve.
Now inject into the dorsal or ventral lymph -sac a few drops of o-i per
cent, solution of sulphate of veratrine. In a few minutes make two
muscle-nerve preparations from the posterior limbs. First put the
preparation from the unligatured limb on the myograph plate. Lay
PRACTICAL EXERCISES 815
the nerve on electrodes connected through a short-circuiting key with
the secondary of an induction machine arranged as in Fig. 287. Put
the writing-point en the drum and set it off (fast speed). Open the
short-circuiting key till the nerve has been once stimulated, then close
it again. The curve obtained differs from a normal curve, in that
the period of descent (relaxation) is exceedingly prolonged. Now
connect the preparation from the ligatured limb with the lever, and
take a tracing of a single contraction. Put on a time-tracing with the
electrical tuning-fork (see Figs. 264, 265, p. ,755).
ii. Measurement of the Latent Period of Muscular Contraction. —
(i) For this the drum must travel at a faster speed than usual. It
is most convenient to use a drum rotated very rapidly by a cord
attached to a falling weight or by the recoil of a stretched rubber band
or spring. The arrangement for automatic stimulation described in
Experiment 6 (p. 813) may be employed. Or an electro-magnetic signal
may be connected in the primary circuit of the induction coil so that
when the primary is closed or opened the writing-point of the signal
moves. Arrange the writing-point of the signal on the drum in the
same vertical line as the writing-point of the muscle lever, and in the
same line place the writing-point of a vibrating electric tuning-fork.
The coil is adjusted for single opening shocks as in Experiment 5
(p. 811). Pith a frog, and make a muscle-nerve preparation. Arrange
it on the myograph plate. The muscle, or the nerve very near the
muscle, is to be excited by a single opening shock while the drum is
moving. When the curve has been traced, the latent period is got by
drawing a vertical line through the point at which the curve just begins
to rise from the abscissa line, and another through the signal mark.
The number of vibrations of the tuning-fork included between these
two verticals gives the latent period.
Or (2) use the spring myograph (Fig. 251, p. 746), raising it oa blocks
of wood. Smoke the glass plate over a paraffin flame, or cover it with
paper, and smoke the paper. Connect the knock-over key of the myo-
graph with the primary circuit of an induction coil. Arrange a muscle-
nerve preparation on the myograph plate. Place electrodes below the
nerve as near the muscle as possible, and connect by a short-circuiting
key with the secondary. Bring the writing-point in contact with the
smoked surface of the spring myograph, so as to get the proper pressure.
See that the writing-point of the tuning-fork is in the right position for
tracing time. Then push up the plate so as to compress the spring,
till the rod connected with the frame which carries the plate is held by
the catch.
With the short-circuiting key closed, press the release and allow an
abscissa line to be traced. Again shove back the frame till it is caught.
Push home the rod by means of which the prongs of the tuning-fork are
separated, and rotate it through 90°. Close the knock-over key, open
the short-circuiting key, shoot the plate again, and a muscle-curve and
time-tracing will be recorded. Again close the short-circuiting key,
withdraw the writing-point of the tuning-fork, push back the plate,
close the trigger key, then open the short-circuiting key, and, holding
the travelling frame with the hand, allow it just to open the knock-
over and stimulate the nerve. The writing-point now records a vertical
line (or, rather, an arc of a circle), which marks on the tracing the
moment of stimulation. The latent period is obtained by drawing a
parallel line (or arc) through the point of the muscle-curve where it just
begins to diverge from the abscissa line. The value of the portion of the
time-tracing between these two lines can be readily determined, and
is the latent period.
8i6 MUSCLE AND NERVE
12. Summation of Stimuli. — Arrange two knock-over keys on the
spring myograph at such a distance from each other that the plate
travels frcm one to the other in a time less than the latent period.
Connect each key with the primary circuit of a separate induction coil
having a couple of Daniells in it. Join two of the binding-screws of
the secondaries together; connect the other two through a short-
circuiting key with electrodes, on which the nerve of a muscle-nerve
preparation is arranged. Push up the secondaries till the break shocks
obtained on opening the two knock-over keys are maximal. Then
shoot the plate as described in n, first with one trigger key closed, and
then with both. The curves obtained should be of the same height in
the two cases, as a second maximal stimulus falling within the latent
period is ignored by the nerve or muscle. Repeat the experiment with
submaximal stimuli — i.e., with such a distance of the coils that opening
of either trigger key does not cause as strong a contraction as is caused
when the coils are closer. The curve will now be higher when the two
shocks are thrown in successively than when the nerve is only once
stimulated. This shows that (submaximal) stimuli can be summed in
the nerve. The same could be demonstrated for muscle (p. 756).
13. Superposition of Contractions. — Smoke a drum arranged for auto-
matic stimulation as in Fig. 287. Adjust the brass points with a
distance of, say, i centimetre between them, so that a second stimulus
may be thrown into the nerve at an interval greater than the latent
period of muscle. Put two Daniells in the primary circuit. Lay the
nerve of a muscle-nerve preparation on electrodes connected through a
short-circuiting key with the secondary. Allow the drum to revolve
(fast speed) ; open the short-circuiting key till both brass points have
passed the projecting wire, then close it. Now bend back the second
brass point, and take a tracing in which the first curve is allowed to
complete itself. This will not rise as high as the second curve obtained
when the two stimuli were thrown in. Repeat the experiment with
varying intervals between the brass points — that is, between the two
successive stimuli. Put on a time-tracing with the electrical tuning-
fork. (For specimen curve, see Fig. 266, p. 756.)
14. Composition of Tetanus. — (a) Adjust a muscle-nerve preparation
on a myograph plate, the nerve being laid on electrodes connected
through a short-circuiting key with the secondary of an induction
machine, the primary circuit of which contains a Daniell cell and is
arranged for an interrupted current (Fig. 93, p. 200). The lever should
be shorter than that used for the previous experiments, or the thread
should be tied in a hole farther from the axis of rotation, so as to give
less magnification of the contraction. Set the Neef's hammer going,
let the drum revolve (slow speed), and open the key in the secondary.
The writing-point at once rises, and traces a horizontal or perhaps
slightly-ascending line. Close the short-circuiting key, and the lever
sinks down again to the abscissa line. If it does not quite return, it
should be loaded with a small weight. This is an example of complete
tetanus.
(b) Connect the spring shown in Fig. 289 with one of the upper
terminals of the primary coil, and the mercury cup with the other.
Fasten the end of the spring in one of the notches in the upright piece
of wood by means of a wedge, so that its whole length can be made to
vibrate. Let the drum off, set the spring vibrating by depressing it
with the finger, then open the key in the secondary. The muscle is
thrown into incomplete tetanus, and the writing-point traces a wavy
curve at a higher level than the abscissa line. Close the short-circuiting
key, and the iever falls to the horizontal. Repeat the experiment with
PRACTICAL EXERCISES
817
the spring fastened, so that only f , £, £, J of its length is free to vibraie.
The rate of interruption of the primary circuit increases in proportion
to the shortening of
the spring, and the
tetanus becomes more
and more complete,
till ultimately the
writing -point marks
an unbroken straight
line. Put on a time-
tracing by means of
an electro - magnetic
marker connected
with a metronome
beating seconds or
half-seconds (Fig. 88,
p. 195). (For speci-
men curves, see Fig.
267, p. 757-)
15. Contraction of
Smooth Muscles —
(i) Spontaneous
Rhythmical Contrac-
tions. — Immerse in
oxygenated Ringer's
solution a ring of
Fig. 289. — Arrangement for Tetanus. A, upright with
notches, in which the spring S is fastened (shown in
section); C, horizontal board to which A is attached,
and in a groove in which the mercury-cup E slides.
The primary coil P is connected with E, and through
a simple key, K, with the battery B, the other pole
of which is connected with the end of the spring.
The wires from the secondary coil, P', go to a short-
circuiting key, K', from which the wires F go off to
the electrodes.
oesophagus obtained
immediately after death from a cat, or, still better, from a chicken. Or
a segment of rabbit's intestine may be employed as described on p. 456.
Use the arrangement
described on p. 456. In
the case of the cat's oeso-
phagus the ring should
be taken from the lower
half of the oesophagus,
since the upper portion
contains purely striated
muscle. Obtain tracings
of the rhythmical con-
tractions on a slowly-
moving drum (Fig. 290).
(2) Fix one end of
a piece of cat's oeso-
phagus, 2 to 5 centi-
metres long, to a muscle-
clamp in a moist
chamber, and the other
end to a lever writing
on a drum. Connect
thin copper wires from
the secondary coil of an
inductorium with the Fig. 290. — Rhythmical Contractions of (Esophagus of
two ends of the piece Chicken (Botazzl).
of oesophagus. Take
tracings to show (a) the curve of a single contraction caused by a single
make or break shock, with estimation of the latent period, as in Experi-
ment ii, p. 815; (b) summation, as in Experiment 12, p. 816; (c) genesis
52
8iS MUSCLE AND NERVE
of tetanus, as in Experiment 14, p. 816; (d) the relations between
strength of stimulus and amount of contraction. For this last experi-
ment the drum should be stationary while the contraction is being
recorded, and should be allowed to move a little between successive
contractions. Begin with the secondary at such a distance from the
primary that a contraction is just caused by a break shock. Then
gradually increase the strength of the stimulus (always using the break)
till maximum contraction is obtained. The gradual increase in the
response is very clearly seen with the cesophageal preparation (Waller).
For further experiments on the contraction of smooth muscle, see
pp. 66 and 457.
1 6. Velocity of the Nerve-Impulse. — Use the spring myograph
(Fig. 251, p. 746) or a very rapidly rotating drum. Make a muscle-
nerve preparation from a large frog (preferably a bull-frog), so that the
sciatic nerve may be as long as possible. Connect the knock-over key
with the primary circuit of an induction machine, which should contain
Fig. 291. — Arrangement for Measuring the Velocity of the Nerve-Impulse. A, travel
ling plate of spring myograph; M, muscle lying on a myograph plate; N, nerve
lying on two pairs of electrodes, E and E'; C, Pohl's commutator without cross-
wires; K, knock-over key of spring myograph (only the binding-screws shown);
K', simple key in primary circuit; B, battery; P, primary coil; S, secondary coil.
a single Daniell cell. Arrange two pairs of fine electrodes under the
nerve on the myograph plate, one near the muscle, the other at the
central end. Connect the electrodes with a Pohl's commutator (with-
out cross-wires), the side-cups of which are joined to the terminals of
the secondary coil, as shown in Fig. 291. By tilting the bridge of the
commutator the nerve may be stimulated at either point. Great care
must be taken to keep the nerve in a moist atmosphere by means of wet
blotting-paper or a moist chamber; but at the same time it must not
lie in a pool of salt solution, as twigs of the stimulating current would
in this case spread down the nerve; and we could never be sure that
the apparent was always the real point of stimulation. The writing-
points of the lever and tuning-fork having been adjusted to the smoked
plate, as in n (p. 815), the bridge of the Pohl's commutator is arranged
for stimulation of the distal point of the nerve, the plate is shot with
the short-circuiting key in the secondary closed, and an abscissa line
and time-curve traced. Then the writing-point of the fork is removed
and the plate again shot with the key in the secondary open, and a
PRACTICAL EXERCISES 819
muscle-curve is obtained. The commutator is now arranged for stimu-
lation of the central end of the nerve, and another muscle-curve taken.
Vertical lines are drawn through the points where the two curves just
begin to separate out from the abscissa line. The interval between
these lines corresponds to the time taken by the nerve-impulse to travel
along the nerve from the central to the distal pair of electrodes. Its
value in time is given by the tracing of the tuning-fork. The length of
the nerve between the two pairs of electrodes is now carefully measured
with a scale divided in millimetres, and the velocity calculated (p. 793).
17. Chemistry of Muscle. — Mince up some muscle from the hind-legs
of a dog or rabbit (used in some of the other experiments), of which
the bloodvessels have been washed out by injecting 0*9 per cent, salt
solution through a cannula tied into the abdominal aorta until the
washings are no longer tinged with blood. To some of the minced
muscle add twenty times its bulk of distilled water, to another portion
ten times its bulk of a 5 per cent, solution of magnesium sulphate.
Let stand, with frequent stirring, for twenty-four hours. Then strain
through several folds of linen, press out the residue, and filter through
paper, (i) With the filtrate of the watery extract make the following
observations :
(a) Reaction. — To litmus-paper acid.
(b) Determine the temperatures at which coagulation of the various
proteins in the extract takes place, according to the method described
on p. 9.* Put some of the water}' extract in the test-tube, and heat
the bath, stirring the water in the beakers occasionally with a feather.
Note at what temperature a coagulum first forms. It will be about
47° C. Filter this off, and again heat; another coagulum will form at
56° to 58°. Filter, and heat the filtrate; a third slight coagulum may
be formed at 60° to 65° C., but this represents merely a residue of the
myosinogen which was left in solution at the previous heating. A
fourth precipitate (of serum-albumin) will come down at 70° to 73°.
Saturate some of the watery extract with magnesium sulphate ; a large
precipitate will be formed, showing the presence of a considerable
amount of globulin. Filter off the precipitate and heat the filtrate;
coagulation will again occur at very much the same temperatures as
before, although the total amount of precipitate will be less. Note in
particular that there is still some precipitate at 47° to 50°. Paramyo-
sinogen possesses some of the characters of both globulins and albumins,
for it is partially but not entirely precipitated by saturation with
magnesium sulphate, and is not precipitated by sodium chloride.
(2) (a) Test the reaction of the magnesium sulphate extract. It
will usually be faintly acid to litmus.
(b) Heat some of it. Precipitates will be obtained at the same tem-
peratures as in (i) (b), but those at 47° to 50° and 56° to 58° will be
more abundant. Of the two, that at 47° to 50° will usually be the
larger when time is given for it to come down and the heating is gradual.
(c) Dilute some of the magnesium sulphate extract with three times,
another portion with four times, and another with five times, its volume
of water in a test-tube, and put in a bath at 40° C. Coagulation or
* It should be remembered that the temperature of heat-coagulation of
any substance is by no means an absolute constant. It depends on the
reaction, the proportion and kind of neutral salts present, perhaps on the
strength of the protein solution and the manner of heating. A solution oi
egg-albumin, e.g., can be coagulated at a temperature much below 70° when
it is heated for a week. Small differences in the temperature of heat-coagula-
tion, unless supported by well-marked chemical reactions, are not enough
to characterize protein substances as chemical individuals.
820 MUSCLE AND NERVE
precipitation will occur in one or all of these test-tubes. To another
test-tube of the extract diluted in the proportion which has given the
best ' muscle-clot ' add a few drops of a dilute solution of potassium
oxalate, and place in a bath at 40°. Coagulation occurs as before.
Filter off the clot from all the test-tubes. The filtrate is the ' muscle-
serum,' and yields a precipitate of serum-albumin at 70° to 73° C.
(3) Myosinogen, like other globulins, is insoluble in distilled water,
but soluble in weak saline solutions. Saturation with neutral salts like
sodium chloride and magnesium sulphate precipitates myosinogen, but
not albumin, from its solutions; saturation with ammonium sulphate
precipitates both. Verify the following reactions of myosinogen, using
the original magnesium sulphate extract of the muscle :
(a) Dropped into water, it is precipitated in flakes, which can be
redissolved by a weak solution of a neutral salt (say 5 per cent, mag-
nesium sulphate).
(b) When a solution of myosinogen is dialyzed, it is after a time pre-
cipitated on the inside of the dialyzer as the salts pass out.
(c) If a piece of rock-salt is suspended in a solution, the myosin
gradually gathers upon it, diffusion of the salt out through the precipi-
tated myosin always keeping a saturated layer around it.
(d) Saturate a solution containing myosinogen with crystals of
magnesium sulphate, stirring or shaking at frequent intervals. The
myosinogen is precipitated.
(e) Without adding any salt, simply shake a myosinogen solution
vigorously; a certain amount of the myosinogen will be precipitated
and the solution will become turbid. This reaction can also be ob-
tained with solutions of other proteins, such as albumins (Ramsden).
Extracts qualitatively similar to those obtained from the muscles
of a freshly-killed animal can be got from muscles that have entered
into rigor, but the quantity of the various proteins going into solution
is less.
18. Reaction of Muscle in Rest, Activity, and Rigor Mortis. — (a) Take
a frog's muscle, cut it across, and press a piece of red litmus-paper on
the cut end; it is turned blue. Yellow turmeric paper is not affected.
(b) Immerse another muscle in physiological salt solution (0-75 per
cent, for frog's tissues) at 40° to 42° C. It becomes rigid. The reaction
becomes acid to litmus-paper, and also turns brown turmeric paper
yellow.
(c) Plunge another muscle into boiling physiological salt solution.
It becomes harder than in (b).
(d) Stimulate another muscle with an interrupted current from an
induction machine (Fig. 93, p. 200), till it no longer contracts. The
reaction is now acid to litmus-paper. Brown turmeric paper may also
be turned yellow.
(e) To demonstrate the formation of lactic acid in muscle in heat
rigor or fatigue, perform the following experiment: Pith a frog, and
afterwards leave it for half an hour at rest, so that the lactic acid pro-
duced in the movements connected with the pithing operation may
disappear from the muscles. See that the circulation in the hind-limbs
is not interfered with by pressure or flexion. Then remove both hind-
limbs. Carefully, but rapidly, remove the muscles of one from the
bones with as little manipulation as possible. Immediately place them
in a small mortar cooled in ice, and containing some sand and 20 or
30 c.c. of ice-cold 95 per cent, alcohol, and quickly grind them up.
Produce heat rigor (p. 777) of the muscles of the other hind-limb, or
fatigus them with induction-shocks, and then grind them up under
alcohol in the same way. P'ilter the alcoholic extracts, and then
PRACTICAL EXERCISES 821
evaporate them to dryness on the water-bath. Rub up the residues
with a few c.c. of hot water. Add to each aqueous extract a small
quantity (say a decigramme) of finely powdered charcoal. Then heat
each extract to boiling in a test-tube, and filter. Evaporate the
filtrates to dryness, and apply
Hopkins 's Reaction for Lactic Acid. — The reagents required are (i) a
very dilute alcoholic solution of thiophene (C4H4S) (10 to 20 drops in
100 c.c.); (2) a saturated solution of copper sulphate; and (3) ordinary
strong sulphuric acid.
Have ready a glass beaker containing water briskly boiling. Place
about 5 c.c. of strong sulphuric acid in a test-tube, with i drop of the
copper sulphate solution.* Add to the mixture a few drops of the
solution to be tested, and shake well.f
(In the case of the muscle extracts the dry residues aro dissolved in
the 5 c.c. of strong sulphuric acid, the acid transferred to test-tubes,
and the test proceeded with by the addition of the copper sulphate
solution, etc.)
Now place the test-tube in the boiling water for one to two minutes.
Then cool it well under the cold-water tap, and add 2 or 3 drops of
the thiophene solution from a pipette. Replace the tube in the boiling
water, and immediately observe the colour. If lactic acid is present,
the liquid rapidly takes on a bright cherry-red colour, which is only
permanent if the test-tube be cooled immediately after its appearance.
The tube should always be cooled as described, before addition of the
thiophene, as the gradual appearance of the colour on re-warming
makes the test more delicate.
(The extract of the resting limb generally gives a negative, that of
the other a strongly positive, reaction.)
* The copper sulphate is added to hasten the oxidation that follows.
f For practice use a i per cent, alcoholic solution of lactic acid. The test
cannot be applied directly to material which chars with the strong sulphuric
acid used . In this case preliminary extraction of the lactic acid is necessary.
Alcohol should be used as the solvent, or if ether is employed it must first be
well washed to remove aldehyde-yielding products, since the colour-change is
due to an aldehyde reaction with thiophene.
CHAPTER XV
ELECTRO-PHYSIOLOGY
A LITTLE more than a hundred years ago the foundation both of electro-
physiology and of the vast science of voltaic electricity was laid by a
chance observation of a professor of anatomy in an Italian garden. It
is indeed true that long before this electrical fishes were not only
popularly known, but the shock of the torpedo had been to a certain
extent scientifically studied. But it was with the discovery of Galvani
of Bologna that the epoch of fruitful work in electro-physiology began.
Engaged in experiments on the effect of static and atmospheric elec-
tricity in stimulating animal tissues, he happened one day to notice
that some frogs' legs, suspended by copper hooks on an iron railing,
twitched whenever the wind brought them into contact with one of
the bars (p. 842). He concluded that electrical charges were developed
in the animal tissues themselves, and discharged when the circuit was
completed. Volta, professor of physics at Pa via, fixing his attention on
the fact that in Galvani's experiment the metallic part of the circuit
was composed of two metals, maintained that the contact of these was
the real origin of the current, and that the tissues served merely as
moist conductors to complete the circuit ; and after a controversy lasting
for more than a decade, he finally clinched his argument by constructing
the voltaic pile, a series of copper and zinc discs, every two pairs of
which were separated by a disc of wet cloth, or paper moistened with salt
solution. The pile yielded a continuous current of electricity. ' So,'
said Volta, ' it is clear that the tissue in Galvani's experiment only acts
the part of the cloth.' Galvani, however, had shown in the meantime
that contraction without metals could be obtained by dropping the nerve
of a preparation on to the muscle (p. 842) ; and it soon began to be recog-
nized that both Galvani and Volta were in part right, that the tissues
produce electricity, and that the contact of different metals does so
too. Although it is curious to note how completely the growth of
that science of which Volta's discovery was the germ has overshadowed
the parent tree planted by the hand of Galvani, yet animal electricity
has been deeply studied by a large number of observers, and many
interesting and important facts have been brought to light.
Since it is in muscle and nerve that the phenomena of electro-
physiology are seen in their simplest expression, and have been
chiefly studied, we shall develop the fundamental laws with reference
to muscle and nerve alone, and afterwards apply them to other
excitable tissues.
i. All points of an uninjured resting muscle or nerve are approxi-
mately at the same potential (or iso- electric). In other words, if any
822
DEMARCATION CURRENT
823
two points are connected with a galvanometer by means of un-
polarizable electrodes, little or no current is indicated. (Although
it is scarcely possible to isolate a muscle without its showing some
current, the more carefully the isolation is performed, the feebler
is the current; and between two points of the inactive, uninjured
ventricle of the frog's heart no electrical difference has been found.
Frogs' nerves kept ten to twenty hours after excision in physiological
salt solution to which a little calcium salt and frog's blood have
been added, are absolutely iso-electric.)
2. Any uninjured point of a resting muscle or nerve is at a different
potential from any injured point. The difference of potential is such
that a current will pass through the galvanometer from uninjured to
injured point and through the tissue from injured to uninjured point
(current of rest, or demarcation current, or injury response) (Fig. 292).
3. Any unexcited point of a muscle or nerve is at a different potential
from any excited point, and any less excited point is at a different
Fig. 292. — A, uninjured, B, injured,
portion of nerve; G, galvanometer.
The large arrows show direction of
demarcation current or current of
rest, the small arrows direction of
negative variation or action current.
Fig. 293. — Diagram of Currents of
Rest in a Regular Muscle, or Muscle
Cylinder. E, equator. The dotted
lines join points at the same po-
tential, between which there is no
current.
potential from any more excited point. The difference of potential
is such that a current will pass through the galvanometer to the
excited from the unexcited or less excited point (action current,
or negative variation, or excitatory electrical response).
It has been customary in physiological writings to speak of the
electrical change in injured or active tissue as a negative one, because
when the tissue is led off to a galvanometer the current passes from
the galvanometer to the injured or excited portion of the tissue.
It may be called with greater precision ' galvanometrically negative.'
It is in this sense that we shall employ the term.
The best object for experiments on the demarcation current is a
straight-fibred muscle like the frog's sartorius. If this muscle be taken,
and the ends cut off perpendicularly to the surface, a muscle-prism or
muscle-cylinder is obtained (Fig. 293). The strongest current is got
when one electrode is placed on the middle of either cross-section, and
the other on the ' equator ' — that is, on a line passing round the longi-
tudinal surface midway between the ends. The direction of this
current is from the cross-section towards the equator in the muscle.
If the electrodes are placed on symmetrical points on each side of the
equator, there is no current.
824 ELECTRO-PHYSIOLOGY
Current of Action, or Negative Variation. — When a muscle or
nerve is excited, an electrical change sweeps over it in the form of
a wave. Suppose two points, A and B (Fig. 294), on the longi-
tudinal surface of a muscle to be connected with a capillary electro-
meter (p. 729), the movements of the mercury being photographed
on a travelling surface — for example, a pendulum carrying a sensitive
plate. Let the muscle be excited at the end, so that the wave of
excitation will be propagated in the direction of the arrow. The
wave will reach A first, and while it has not yet reached B, A will
Fig. 294. — Diagram to illustrate Propagation of the Electrical Change along an
Active Muscle or Nerve. Suppose AB to be a horizontal bar representing the
muscle or nerve. Let C be a curved piece of wood representing the curve of the
electrical change at any point. Let W, W' be two glass cylinders connected by
a flexible tube, the whole being filled with water. Suppose the rims of the
cylinders originally to touch AB at the points A and B, and let them be movable
only in the vertical direction. The level of the water being the same in both,
there is no tendency for it to flow from one to the other. This represents the resting
state of the tissue when A and B are symmetrical points. Now let C be moved
along the bar at a uniform rate. The cylinder W, being free to move down, but
not horizontally, will be displaced by C, and, if it is kept always in contact with
its curved margin, will, after describing the curve of the electrical variation,
come again to rest in its old position at A. B will do the same when C reaches
it. But since C reaches A before B, the level of the water in B will at first be
higher than that in A, and water will flow from B to A as the current flows
through the galvanometer. This will correspond to the time during which the
point of the tissue represented by A would be galvanometrically negative to a
point represented by B. Later on, when C has reached the position shown by
the dotted lines, the level of the water in A will be higher than that in B, and a
flow will take place in the opposite direction to the first flow. This corresponds
to a second phase of the electrical variation.
become negative to B. If there is a resting difference of potential
between A and B, this will be altered, the new and transitory differ-
ence adding itself algebraically to the old. When the wave reaches
B, it may already have passed over A altogether, and B now be-
coming negative to A, there will be a movement of the meniscus
of the electrometer in the opposite direction. This is called the
NEGATIVE VARIATION
825
diphasic current of action. If the wave has not passed over A before
it reaches B, as would in general be the case in an actual experiment,
there will be first a period during which A is relatively negative to
B (first phase) ; this will end as soon as B has become iso-electric
with A, and will be succeeded by a period during which B is rela-
tively negative to A (second phase). Since the wave takes time to
reach its maximum, it is evident that a well-marked first phase will
be favoured when the interval between its arrival at A and at B is
long, for in this case A will have a chance of becoming strongly
negative while B is still normal. Similarly, if A has again become
normal, or nearly normal, before the maximum negative change has
passed over B, a strong second phase will be favoured. The heart-
muscle, accordingly, where the wave of contraction, and its accom-
panying electrical change, move with comparative slowness, te
better suited for showing a well-marked diphasic variation than
skeletal muscle, and still better suited than nerve. In the gastroc-
T*^* • • • r»
Fig. 295. — Photographic Electrometer Curves from Sartorius Muscle (Sanderson).
The darkly-shaded curve represents the diphasic variation of the uninjured
muscle; the lightly-shaded curve the monop basic variation of the muscle after
injury of one end. The toothed curve at the top is the time-tracing registered by
photographing the prong of a tuning-fork vibrating five hundred times a second.
nemius muscle of the frog, when excited through its nerve, the elec-
trical response begins about T> **'
R
Fig. 314. — Electro-Cardiogram from Man (String Galvanometer) (Lewis). From a
case of paroxysmal tachycardia. The heart-rate was 200 a minute. The upper
notched line is the time-trace in one-fifth seconds.
electro-cardiograms, (Fig. 309) is reproduced for their historical interest.
In their main features it is obvious that they agree with the records
obtained by the string galvanometer. The electro-cardiograms are
distinctly affected by exercise and by the position of the body, and very
markedly in disease.. The galvanometer may be connected with the two
ELECTRO-CARDIOGRAM
837
hands, or, better, with the right hand and the left foot. The two feet
are the most unfavourable combination. The reason is obvious from
the direction of the long axis of the heart, which determines the
direction of the lines of flow of currents due to differences of potential
between base and apex (Fig. 310).
Relation of the Waves of the Electro-Cardiogram to the Mechanical
Events in the Cardiac Cycle. — There is evidence that the excitation pro-
cess with its associated electrical change spreads over the auricle from the
sinus node, followed at each point by the mechanical change or contrac-
tion, in such a manner that the portions nearer the node begin to relax
before the more distal units have finished contracting. When a tracing
of the approximation of two distant points of the auricle is taken,
the total shortening represents the algebraic sum of the contractions
and relaxations of all the muscular units between the two points.
Fig- 3I5- — Upper curve, pressure in right auricle. Second curve from top, right
auricular myogram; the down-stroke corresponds to contraction. Third curve,
ventricular sounds. Bottom curve, electrocardiogram, lead II (left hind and
right fore leg) (Wiggers).
Electrical effects obtained by leading off from the heart in any particu-
lar way must also be more or less complex resultants of the changes at
different points. Certain general relations, however, have been estab-
lished between the mechanical events and the electro-cardiogram. In
Fig. 315 are shown simultaneous records of the contraction of the
auricle (auricular myogram), the intra-auricular pressure, the heart
sounds and the electro-cardiogram (Wiggers). The first electrical
variation, commencing at i, is seen to precede the rise of pressure in
the auricle, 2, by a definite interval (about 0-02 sec.), and the onset of
the mechanical shortening ,3, by a somewhat greater interval (0-03 sec.).
The length of these intervals is, of course, not precisely the same in
different experiments.
The relation of the beginning of the rise of intra-auricular pressure
and of the beginning of the mechanical systole of the auricles to the
838 ELECTRO-PHYSIOLOGY
P wave of the electro-cardiogram (the wave specially associated with
the passage of excitation over the auricle) is also slightly variable.
Roughly, the apex of the P wave may be taken as indicating the onset
of the auricular systole. The relation between the end of the auricular
systole, 4, and the electro-cardiogram, is still more variable, but in
general it falls not far from the summit of the R wave (a wave specially
associated with the passage of the excitation over the ventricle) . This
shows that the auricular systole still continues at a time when the ex-
citation process has already made considerable progress in the ventricle.
The mechanical contraction of the ventricle, as shown in Fig. 315, by
the position of the vibrations corresponding to the first sound, follows
very promptly the completion of the auricular systole.
Central Nervous System. — It was discovered by du Bois-Reymond
that the spinal cord, like a nerve, shows a current of rest between longi-
tudinal surface and cross-section, and that a current of action is caused
by excitation. Setschenow stated that when the medulla oblongata
of the frog was connected with a galvanometer, spontaneous variations
occurred which he supposed due to periodic functional changes in its
grey matter. Gotch and Horsley have made experiments on the spinal
cords of cats and monkeys. Leading off from an isolated portion of
the dorsal cord to the capillary electrometer, and stimulating the
' motor ' region of the cortex cerebri, they obtained a persistent nega-
tive variation followed by a series of intermittent variations. This
agrees remarkably with the muscular contractions in an epileptiform
convulsion started by a similar excitation of the cortex, which consist
of a tonic spasm followed by clonic or phasic (interrupted) contractions.
By means of the galvanometer, the same observers have made in-
vestigations on the paths by which impulses set up at different points
travel along the cord. To these we shall have to refer again (p. 895).
Electrical Phenomena of Glands. — These have been studied with any
care chiefly in the submaxillary gland and in the skin, although the
liver, kidney, spleen, and other organs also
show currents when injured. In the sub-
maxillary gland the hilus is galvanometrically
positive to any point on the external surface
of the gland ; a current passes from hilus to
surface through the galvanometer, and from
surface to hilus through the gland (Fig. 316).
Fig. 316. — Current of Sub- When the chorda tympani is stimulated with
maxillary Gland. rapidly - succeeding shocks of moderate
strength, there is a positive variation — i.e., the
hilus becomes still more positive to the surface. This variation can
be abolished by a small dose of atropine.
Skin Currents. — So far as has been investigated, the integument of all
animals shows a permanent current passing in the skin from the external
surface inwards. This is feebler in skin which possesses no glands. In
skin containing glands the current is chiefly, but not altogether, secre-
tory. As such, it is affected by influences which affect secretion, a
positive variation being caused by excitation of secretory nerves — e.g.,
in the pad of the cat's foot by stimulation of the sciatic. The deflection
obtained when a finger of each hand is led off to the galvanometer,
which was at one time looked upon as a proof of the existence of currents
of rest in intact muscles, is due to a secretion current.
Of more doubtful origin is the current of ciliated mucous membrane,
which has the same direction as that of the skin of the frog and the
mucous membrane of the stomach of the frog and the rabbit — viz., from
ciliated to under surface through the tissue, or from ciliated surface to
cross-section, if that is the way in which it is led off. The current is
ELECTROMOTIVE PHENOMENA OF THE EYE
839
strengthened by induction shocks, by heating, and in general by influ-
ences which increase the activity of the cilia. Some circumstances
point to the goblet-cells in the membrane as the source of the current;
but, on the whole, the balance of evidence is in favour of the cilia being
the chief factor (Erigelmann), although the mucin-secreting cells may
be concerned, too. Electrical changes associated with secretion have
been observed in the frog's tongue on excitation of the glosso-pharyngeal
nerve.
Eye- Currents. — If two unpolarizable electrodes connected with a
galvanometer are placed on the excised eye of a frog or rabbit, one on
the cornea and the other on the cut optic nerve, or on the posterior
surface of the eyeball, it is found that a current passes in the eye from
optic nerve to cornea, the fundus of the eye being therefore negative
as regards the cornea (Fig. 317). The current has the same direction
if the anterior electrode is placed on the an-
terior surface of the retina itself, the front of
the eyeball being cut away, or if one electrode
is in contact with the anterior and the ether
with the posterior surface of the isolated
retina. There is nothing of special interest in
this ; but the important point is that if light be
now allowed to fall upon the eye, or upon the
isolated retina, characteristic electrical changes
are caused. These are spoken of as the photo-
electric reaction, and are best studied by means
of the string galvanometer. The features of
the curve representing the photo-electric reaction vary with the duration
and intensity of the illumination and with the previous condition of the
eye as regards illumination. A careful analysis of the curves obtained
under different conditions supports the hypothesis that there occur in
the eye three separate processes, which may for convenience be con-
sidered to depend upon the existence in the retina of three separate
photo-chemical substances. When light of moderate intensity is
allowed to act upon an eye which has not shortly before been exposed
g. 317. — Eye-Current.
Fig. 318.— Photo -Electric Reaction of Frog's Eye (Einthoven and Jolly). The
duration of the flash (of green light) was o-oi second. The eye had been pre-
viously in the dark, i millimetre of the abscissa corresponds to 0-5 second,
i millimetre of the ordinate to 10 microvolts. Curve to be read from left to right.
to strong light, a form of curve is obtained which seems to represent
the combined reaction of the three substances (Einthoven and Jolly)
(Fig. 318). After a latent period a small preliminary negative deflec-
tion A is observed (downward movement of the string). This is at once
840
ELECTRO-PHYSIOLOGY
followed by a much larger upward movement (positive variation) in
the same direction as the resting effect, the fundus becoming relatively
more negative to the cornea than before. After the peak B has been
reached, the curve sinks first rapidly, then more gradually, but soon
mounts again, and reaches a second maximum C, vhichis higher than B
(second positive variation). Finally, the curve descends to its original
level.* The photo-electric reaction is substantially the same in all
vertebrate eyes hitherto investigated. In the cephalopcd retina, too,
the only important electrical change on illumination is in the same
direction as the resting effect.
The reaction depends upon the retina alone, and does not occur
when it is removed. Bleaching of the visual purple does not much
affect it, so that it is not connected with chemical changes in this
substance. Its seat must be the layer of rods and cones, since in the
Fig. 319. — Diagram showing Direction of Shock in Gymnotus.
cephalopods the structure called the retina contains only this layer, the
other layers of the vertebrate retina being represented in the optic nerve
and ganglion (Beck). Of the spectral colours, yellow light causes the
largest variation; blue, the least; but white light is more powerful than
either (Dewarand McKendrick). (For 'visual purple, 'see Chap. XVIII.)
Electric Fishes. — Except lightning, the shocks of these fishes were
probably the first manifestations of electricity observed by man. The
Torpedo, or electrical ray, of the coasts of Europe was known to the
Greeks and Romans. It is mentioned in the writings of Aristotle and
Pliny, and had the honour of
being described in verse 1,500
years before Faraday made the
first really exact investigation
of the shock of the Gymnotus,
or electric eel, of South America.
Another of the electric fishes,
Malapterurus electricus, al-
though found in many of the
African rivers, the Nile in par-
ticular, and known forages, was
scarcely investigated till fifty
years ago.
In all these fishes there is a
special bilateral organ immediately under the skin, called the electrical
organ. It is in this that the shock is developed. It consists of a
series of plates arranged parallel to each other. To one side of each
plate a branch of the electrical nerve supplying each lateral half of
* In the figure the last portion of the curve while it is still slowly descending
has not been reproduced.
Fig. 320. — Diagram showing Direction of
Shock in Malapterurus.
ELECTRIC FISHES 841
the organ is distributed, so that each half of the organ represents a
battery of many cells arranged in series.
In Gymnotus the plates are vertical, and at right angles to the long
axis of the fish, and the nerves are distributed to their posterior surface ;
the shock passes in the animal from tail to head. In Malapterurus,
although the direction of the plates is the same, and the nerve-supply
is also to the posterior surface, the shock passes from head to tail.
In Torpedo, the plates or septa dividing the vertical hexagonal prisms
of which each lateral half of the organ consists are horizontal ; the nerve-
supply is to the lower or ventral surface ; and the shock passes from belly
to back through the organ. In all electric fishes the discharge is dis-
continuous; an active fish may give as many as 200 shocks per second.
The electrical nerve of Malapterurus is peculiar. It consists of a
single gigantic nerve-fibre on each side, arising from a giant nerve-cell.
The fibre has an enormously thick sheath, the axis-cylinder forming a
relatively small part of the whole; and the branches which supply the
plates of the organ are divisions of this single axis-cylinder.
The electromotive force of the shock of the Gymnotus may be very
considerable; and even Torpedo and Malapterurus are quite able to
kill other fish, their enemies or their prey. Indeed, Gotch has esti-
mated the electromotive force of i cm. of the organ of Torpedo at
5 volts. Schonlein finds that the electromotive force of the whole
organ may be equal to that of 31 Daniell cells, or 0-08 volt for each
plate, and it is one of the most interesting questions in the whole of
electro-physiol'jgy, how they are pro-
tected from their own currents . There
is no doubt that the current density
inside the fish must be at least as
great as in any part of the water sur-
rounding it, and probably much
greater. The central nervous system
and the great nerves must be struck
by strong shocks, yet the fish itself is Fig. 321. — Diagram showing Direc-
not injured; nay, more, the young in tion of Shock in Torpedo,
the uterus of the viviparous Torpedo
are unharmed. The only explanation seems to be that the tissues of
electric fishes are far less excitable to electrical stimuli than the tissues of
other animals; and this is found to be the case when their muscles or
nerves are tested with galvanic or induction currents. It requires ex-
tremely strong currents to stimulate them ; and the electrical nerves are
more easily excited mechanically, as by ligaturing or pinching, than elec-
trically. In general, too, the shock is morg readily called forth by reflex
mechanical stimulation of the skin than by electrical stimulation. But
that the organ itself is excitable by electricity has been shown by Gotch.
He proved that in Torpedo a current passed in the normal direction
of the shock is strengthened, and a current passed in the opposite
direction weakened, by the development of an action current in the
direction of the shock. And, indeed, a single excitation of the electrical
nerve is followed by a series of electrical oscillations in the organ, which
gradually die away. The latent period of a single shock is about
^J0 second. The skate must be included in the list of electric fishes.
Although its organ is relatively small, and its electromotive force rela-
tively feeble, yet it is in all respects a complete electrical organ. It
is situated on either side of the vertebral column in the tail. The
plates or discs are placed transversely and in vertical planes. The
nerves enter their anterior surfaces; the shock passes in the organ from
anterior to posterior end. Gotch and Sanderson have estimated the
maximum electromotive force of a length of I cm. of the electrical
organ of the skate at about half a volt.
842 ELECTRO-PHYSIOLOGY
Whether the electrical organ is the homologue of muscle or of nerve-
ending, or whether it is related to either, has been much discussed.
Our surest guide in a question of this sort is the study of development;
and researches along this line have shown that there are two kinds oi
electrical organ, one being modified muscle (as in Gymnotus, Torpedo,
and the skate) ; the other transformed skin-glands (as in Malapterurus) .
The scanty blood-supply of the electrical organs in comparison with that
of muscle is noteworthy. In no case do bloodvessels enter the substance
of the plates.
PRACTICAL EXERCISES ON CHAPTER XV.
1 . Galvani's Experiment. — Pith a frog (brain and cord). Cut through
the backbone above the urostyle, and clear away the anterior portion
of the body and the viscera. Pass a copper hook beneath the two
sciatic plexuses, and hang the legs by the hook on an iron tripod. If
the tripod has been painted, the paint must be scraped away where the •
hook is in contact with it. Now tilt the tripcd so that the legs come
in contact with one of the iron feet. Whenever this happens, the
circuit for the current set up by the contact of the copper and iron is
completed, the nerves are stimulated, and the muscles contract (p, 822).
2. Make a muscle-nerve preparation from the same frog. Crush the
muscle near the tendo Achillis, so as to cause a strong demarcation
current. Cut off the end of the sciatic nerve. Then lift the nerve
with a small brush or thin glass rod, and let its cross-section fall on or
near the injured part of the muscle. Every time the nerve touches the
muscle a part of the demarcation current passes through it, stimulates
the nerve, and causes contraction of the muscle (p. 822).
3. Secondary Contraction. — Make two muscle-nerve preparations.
Lay the cross-section of one of the sciatic nerves on the muscle of the
other preparation (Fig. 305, p, 833). Place under the nerve near its
cut end a small piece of glazed paper or of glass rod, and let the longi-
tudinal surface of the nerve come in contact with the muscle beyond
this. Lay the nerve of the other preparation on electrodes connected
with an induction machine arranged for single shocks, with a Daniell
cell and a spring key in the primary circuit (Fig, 283, p. 808). On
closing or opening the key both muscles contract. Arrange the induc-
tion machine for an interrupted current. When it is thrown into one
nerve, both muscles are tetanized; the nerve lying on the muscle whose
nerve is directly stimulated is excited by the action current of the muscle.
4. Demarcation Current and Current of Action with Capillary Elec-
trometer. — (a) Study the construction of the capillary electrometer
(Fig. 235, p. 729). Raise the glass reservoir by the rack and pinion
screw, so as to bring the meniscus of the mercury into the field. Place
two moistened ringers on the binding-screws of the electrometer, open
the small key connecting them, and notice that the mercury moves, a
difference of potential between the two binding-screws being caused
by the moistened fingers.
(b) Demarcation Current. — Set up a pair of unpolarizable electrodes
(Fig. 238, p. 731). Fill the glass tubes about one-third full of kaolin
mixed with physiological salt solution till it can be easily moulded.
To do this, make a piece of the clay into a little roll, which will slip down
the tube. Then with a match push it down until it forms a firm plug.
Next put some saturated zinc sulphate solution in the tubes, above the
clay, with a fine-pointed pipette. Fasten the tubes in the holder fixed
in the moist chamber (Fig. 322). Now amalgamate the small pieces of
zinc wire (p. 197) which are to be connected with the binding-screws of
the chamber. (Or use Porter's ' boot ' electrodes. These are made of
unglazed potter's clay. In use the leg of the boot is half-filled with
PRACTICAL EXERCISES
843
saturated zinc sulphate solution, into which dips a thick amalgamated
zinc wire, in the toot ot the boot is a hollow (or well) which is filled
with physiological salt solution and serves to keep the feet well moist-
ened, with the salt solution. The nerve is laid on the feet of the boots.
When not in use the boots should be kept in physiological salt solution.)
The zincs are now placed in the tubes, dipping into the zinc sulphate.
A piece of clay or blotting-paper moistened with physiological salt solu-
tion is laid across the electrodes to complete the circuit between their
points, and they are connected with the electrometer to test whether
they have been properly set up. There ought to be little, if any, move-
ment of the mercury on opening the side-key of the electrometer. If the
movement is large,
the electrodes are
'polarized,' and must
be set up again. The
second pair of bind-
ing - screws in the
chamber are con-
nected with a pair of
platinum-pointed
electrodes on the one
side, and on the other,
through a short-cir-
cuiting key, with the
secondary coil of an
induction machine ar-
ranged for tetanus.
Next pith a frog
(cord and brain), and
make a muscle-nerve
preparation . Inj ure
Q' B
Fig. 322. — Moist Chamber. E, unpolarizable electrodes
supported in the cork C; M, muscle stretched over the
electrodes and kept in position by the pins A, B, stuck
in the cork plate P; B, binding-screws connected with
galvanometer or capillary electrometer. The other
pair of binding-screws serves to connect a pair of
stimulating electrodes inside the chamber with the
secondary coil of an induction machine.
the muscle near the
tendo Achillis. Lay
the injured part over
one unpolarizable
electrode, and an un-
injured part over the
other. Put a wet sponge in the chamber to keep the air moist, and place
the glass lid on it. Focus the meniscus of the mercury, and open the
key of the electrometer; the mercury will move, perhaps right out of the
field. Note the direction of movement, and, remembering that the
real direction is the opposite of the apparent direction, and that when
the mercury in the capillary tube is connected with a part of the muscle
which is relatively positive to that connected with the sulphuric acid,
the movement is from capillary to acid, determine which is the galvano-
metrically positive and which the negative portion of the muscle (p. 823).
(c) Action Current. — Now, without disturbing its position on the
electrodes, fasten the muscle to the cork or paraffin plate in the moist
chamber by pins thrust through the lower end of the femur and the
tendo Achillis. Lay the nerve on the platinum electrodes. Open the
key of the electrometer, and let the meniscus come to rest. This
happens very quickly, as the capillary electrometer has but little inertia.
If the meniscus has shot out of the field, it must be brought back by
raising or lowering the reservoir. Stimulate the nerve by opening the
key in the secondary circuit ; the meniscus moves in the direction oppo-
site to its former movement.
(d) Repeat (b) and (c) with the nerve alone, laying an injured part
(crushed, cut, or overheated) on one electrode, and an uninjured part
on the other. Of course, the nerve does not need to be pinned.
844 ELECTRO- PH YSIOLOG Y
Clean the unpolarizable electrodes, and he sure to lower the reservoir
of the electrometer ; otherwise the mercury may reach the point of the
capillary tube and run out.
In 4 a galvanometer (p. 726) may be used with advantage by
students, if one is available, instead of the electrometer, the un-
polarizable electrodes being connected to it through a short-circuit-
ing key. The spot of light is brought to the middle of the scale by
moving the control-magnet; or if a telescope-reading is being used, the
zero of the scale is brought by the same means to coincide with the
vertical hair-line of the telescope. The short-circuiting key is then
opened.
5. Action Current of Heart. — Pith a frog (brain and cord). Excise
the heart, and lay the base on one unpolarizable electrode, and the
apex on the other, having a sufficiently large pad of clay on the tips of
the electrodes to insure contact during the movements of the heart, or
having little cups hollowed in the clay and filled with physiological salt
solution, into which the organ dips. Connect the electrodes with the
capillary electrometer and open its key. At each beat of the heart the
mercury will move (p. 833).
6. Electrotonus. — Set up two pairs of unpolarizable electrodes in the
moist chamber. Connect two of them with a capillary electrometer
(or galvanometer), and two with a battery of three or four small Daniell
cells, as in Fig, 304. Lay a frog's nerve on the electrodes. When the
key in the battery circuit is closed, the mercury (or the needle of the
galvanometer) moves in such a direction as to indicate that in the extra-
polar regions parts of the nerve nearer to the
anode are relatively positive to parts more re-
mote, and parts nearer to the kathode are rela-
tively negative to parts more remote. The
direction of movement of the mercury (or gal-
vanometer needle) must be made out first for one
direction of the polarizing current. Then the
latter must be reversed, and the movement of
the mercury (or needle) on closing it again noted
(P Sao/
7. Paradoxical Contraction. — Pith a frog (brain
and cord) . Dissect out the sciatic nerve down to
the point where it splits into two divisions, one
for the gastrocnemius b, and the other for the
peroneal muscles a. Divide the peroneal branch
as low down as possible, and make a muscle-nerve
preparation in the usual way. Lay the central
323- — Paradoxical end of the peroneal nerve on electrodes con-
Contraction, nected through a simple key with a battery of two
Daniell cells. When the peroneal nerve is stimu-
lated, the gastrocnemius muscle contracts. This result is not due to the
current of action, for it is not obtained with mechanical stimulation
of the nerve. But it is not the result of an escape of current, for if the
peroneal nerve be ligatured between the point of stimulation and the
bifurcation, no contraction is obtained. The contraction is really due
to a part of the electrotonic current set up in the peroneal nerve passing
through the fibres for the gastrocnemius, where they lie side by side
in the trunk of the sciatic.
8. Alterations in Excitability (and Conductivity) produced in Nerve
by the Passage of a Voltaic Current through it. — Set up two pairs of
unpolarizable electrodes in the moist chamber. Connect a battery of
two or three Daniell cells, arranged in series through a simple key
PRACTICAL EXERCISES 84$
with the side-cups of a Pohl's commutator with cross-wires in. Con-
nect the commutator to one pair of the unpolarizable electrodes (' the
polarizing electrodes '), as in Fig. 324. The other pair of unpolarizable
electrodes (' the stimulating electrodes ') are to be connected through a
short-circuiting key with the secondary of an induction machine
arranged for tetanus. A single Daniell is put in the primary coil.
Pith a frog (brain and cord), make a muscle-nerve preparation, pin
the lower end of the femur to the cork plate in the moist chamber,
attach the thread on the tendo Achillis to the lever connected with the
chamber through the hole in the glass provided for this purpose, and
arrange the nerve on the electrodes so that the stimulating pair is
between the muscle and the polarizing pair. By moving the secondary,
seek out such a strength of stimulus as just suffices to cause a weak
tetanus when the polarizing current is not closed. Set the drum off
(slow speed), and take a tracing of the contraction. Then close the
polarizing current with a Pohl's commutator so arranged that the
anode is next the stimulating electrodes — i.e., the current ascending in
the nerve. Again open the short-circuiting key in the secondary; the
contraction will now be weaker than before, or no contraction at all
may be obtained. Allow the preparation two minutes to recover,
Fig. 3 H. — Arrangement for showing Changes of Excitability produced by the Voltaic
Current. M, muscle; N, nerve; Ej, Eg, electrodes connected with secondary
coilS; E3, E4, unpolarizable electrodes connected with Pohl's commutator (with
cross-wires) C; B', 'polarizing' battery; B, 'stimulating' battery in primary
circuit P; K, K", simple keys; K', short-circuiting key.
then stimulate again, as a control, without closing the polarizing
current. If the contraction is of the same height as at first, close the
polarizing current with the bridge of the commutator reversed, so
that the kathode is now next the stimulating electrodes. On stimu-
lating, the contraction will now be increased in height. (See Figs. 273.
274, P- 786.)
9. Pfliiger's Formula of Contraction (p. 788). — To demonstrate this,
connect two unpolarizable electrodes, through a spring key and a
commutator, with a simple rheocord (Fig. 286, p. 810), so as to lead
off a twig of a current from a Daniell cell. The unpolarizable elec-
trodes are placed in a moist chamber. A muscle-nerve preparation
is arranged with the nerve on the electrodes and the muscle attached
to a lever. The effects of make and break of a weak current, ascending
and descending, can be worked out with the simple rheocord. The
effects of a medium current will probably be obtained with a single
Daniell connected directly with the electrodes through a key. The
effects of a strong current will be got when three or four Daniells are
connected with the electrodes. Care must be taken to keep the prepara-
tion in a moist atmosphere, and more than one preparation may be
needed to verify the whole formula.
846
ELECTRO-PHYSIOLOG Y
10. Formula of Contraction for (Human) Nerves in Situ. — Connect
eight or ten dry cells in series.* Connect one terminal of the battery
to a large plate electrode, and the other to a small electrode, both
covered with cotton, flannel, or sponge, moistened with salt solution.
Include in the circuit a simple key for making or breaking the current,
and a commutator for changing its direction at will. Leave the key
open. Place the large electrode behind the shoulder (or on the back
of the neck), and the small electrode over the ulnar nerve at the elbow
between the internal cbndyle and the olecranon. Arrange the com-
mutator so that the small electrode shall be the kathode. Close, and
then open the key. If no contraction occurs at closing, the battery
is too weak, and more cells must be added. If contraction occurs at
closing, but not at opening, reverse the commutator, making the small
electrode the anode, and observe whether contraction now occurs at
closing, at opening, or at both. Note also the relative strength of the
various contractions. If the current is ' weak/ the only contraction
will be a closing one when the kathode is over the nerve. If the current
is of ' medium ' strength, a closing kathodic contraction and both
opening and closing anodic contractions will be obtained. With ' strong '
currents contractions will occur at closing and at opening, whether the
kathode or the anode is over the nerve. The contractions will vary
in strength, as described on p. 789. To work out the different cases
of the formula summarized in the table, the number of cells must be
increased or diminished.
Weak Currents.
Medium Currents.
Strong Currents.
KCC
KCC
KCC
—
ACC
ACC
—
AOC
AOC
—
—
KOC
The abbreviations KCC, ACC, are used respectively for kathodic
closing contraction and anodic closing contraction; KOC, AOC, for
kathodic opening contraction and anodic opening contraction. KCC
is stronger than KOC, and ACC than AOC. KCC is stronger than
ACC, and AOC than KOC. Therefore, as the strength of the current
is increased, in the case of normal tissues, KCC is first obtained, then
ACC, then AOC, and finally KOC.
n. Ritter's Tetanus. — Lay the nerve of a muscle-nerve preparation
on a pair of unpolarizable electrodes connected through a simple key
with a battery of three or four small Daniells. Connect the muscle
with a lever. Pass an ascending current (anode next the muscle) for
a few minutes through the nerve, and let the writing-point trace on
a slowly-moving drum. When the current is closed there may be a
single momentary twitch, or the muscle may remain somewhat con-
tracted (galvanotonus) as long as the current is allowed to pass, or it
may continue to contract spasmodically (' closing tetanus '). When
the current is opened the muscle will contract once, and then immedi-
ately relax, or there may be a more or less continued tetanus (Ritter's
qr ' opening tetanus '). If opening tetanus is obtained, divide the
nerve between the electrodes: the tetanus continues. Divide it be-
tween the anode and the muscle: the tetanus at once disappears. This
shows that the seat of the excitation which causes the tetanus is in
the neighbourhood of the anode (p. 831).
* If the laboratory possesses a battery (with rheostat), such as is used by
neurologists, the experiment is more conveniently performed with this.
CHAPTER XVI
THE CENTRAL NERVOUS SYSTEM
IN other divisions of our subject we have been able to follow to a
greater or less extent the processes which take place in the organs
described. The chemistry and the physics of these processes have
bulked more largely in our pages than the anatomy and histology
of the tissues themselves. In dealing with the central nervous
system, we must adopt a method the very reverse of this. Its ana-
tomical arrangement is excessively intricate. The events which
take place in that tangle of fibre, cell, and fibril are, on the other
hand, almost unknown. So that in the description of the physiology
of the central nervous system we can as yet do little more than
trace the paths by which impulses may pass between one portion
of the system and another, and from the anatomical connections
deduce, with more or less probability, the nature of the physiological
nexus which its parts form with each other and the rest of the body.
And here it may be well to remark that, although for convenience
of treatment we have considered the general properties of nerves
in a separate chapter, there is not only no fundamental distinction
between the central nervous system and the outrunners which
connect it with the periphery, but obviously a central nervous
system would be meaningless and useless without afferent nerves
to carry information to it from the outside, and efferent nerves along
which its commands may be conducted to the peripheral organs.
SECTION I. — STRUCTURE OF THE CENTRAL NERVOUS SYSTEM —
HlSTOLOGICAL ELEMENTS.
In unravelling the complex structure of the central nervous
system, we avail ourselves of information derived (i) from its gross
anatomy ; (2) from its microscopical anatomy ; (3) from its develop-
ment ; (4) from what we may call, although the term is open to the
criticism of cross-division, its physiological and pathological
anatomy.
Certain tracts of white or grey matter are differentiated from each
other by the size of their fibres or ceils. For example, the postero-
median column of the spinal cord has small fibres, the direct cere-
847
848 THE CENTRAL NERVOUS SYSTEM
bellar tract large fibres; the large pyramidal cells (giant cells or cells
of Betz), in what we shall afterwards have to distinguish as the ' motor
area ' (p. 950) of the cerebral cortex, are the cells of origin of fibres of
the pyramidal tract subserving the volitional movements of the limbs
and trunk. The pyramidal cells of the ' face area ' are comparatively
small. In general, an efferent or motor nerve-cell is larger the longer
its axon is — e.g., the largest of all the pyramidal cells in the ' motor '
region are found in the portion known as the ' leg area,' from which
the pyramidal fibres have to pass all the way down the cord to the
segments from which the spinal nerves going to the lower limbs arise.
The recent work of Brodman and of Campbell has shown that the
cerebral cortex may be histologically differentiated into regions which
correspond to a great extent to the various functional regions mapped
out by physiological methods (p. 958).
The study of development enables us not only to determine the
homology, the morphological rank, of the various parts of the brain
and cord, but also, by comparison of animals of different grades of
organization, sometimes to decide the probable function and physio-
logical importance of a strand of nerve-fibres or a column of nerve-
cells. It is of special value in helping us to differentiate the various
areas of grey matter on the surface of the brain, and to trace the various
tracts or paths into which the white matter of the central nervous
system may be divided. For the medullary sheath is not developed
at the same time in all the tracts, and a strand of nerve-fibres in which
it is wanting — e.g., the pyramidal tract (p. 878), which is the last of
the spinal tracts to become myelinated — is readily distinguished under
the microscope.
Then, again — and this is what we propose to include under the
fourth head — experimental physiology and clinical and pathological
observation throw light not only on the functions, but also on the
structure, of the central nervous system. For instance, complete or
partial sectioH, or destruction by disease, of the white fibres of the
cord or brain, or of the nerve-roots, or removal of portions of the grey
matter, is followed by degeneration in definite tracts. And since, as
we have already seen, degeneration of a nerve-fibre is caused when it
is cut off from the cell of which it is a process, the amount and dis-
tribution of such degeneration teaches us the extent and position of
the central connections of the given tract. Conversely, the cells in
which a tract of nerve-fibres arises may sometimes be identified by
the alterations in the chromatin (p. 859) and other changes which occur
in them after section of their axons. Particularly in young animals,
removal of a peripheral organ — an eye or a limb — or section of its
nerves, may be followed by atrophy of portions of the central nervous
system immediately related to it.
' Softening ' of a definite portion of the white or grey matter may
also in certain cases be caused by depriving it of its blood-supply by
the injection of artificial emboli, and the resulting degenerations may
then be studied. For instance, fine particles like lycopodium spores
are injected into the abdominal aorta between the origins of the renal
and inferior mesenteric arteries. They are prevented by clamps from
entering these vessels, and, passing through the lumbar arteries, stick
in the branches of the anterior spinal artery, and cause softening
mainly of the grey matter of the lumbar portion of the cord. When
the abdominal aorta of a rabbit is temporarily compressed (for about
an hour) below the origin of the renal arteries, the grey matter of the
corresponding portion of the cord is so seriously injured that it and
the fibres that arise from it degenerate, while the fibres whose cells of
325- — Formation of the Neural
Canal at an Early Stage (Beard).
origin are not situated in this part of the grey matter are not affected,
or at least completely recover.
Certain tracts may also be marked out by means of the electrical
variation, which gives token of
the passage of nervous impulses
along them when portions of the
central nervous system or peri-
pheral nerves are stimulated
(Horsley and Gotch) .
Development of the Central
Nervous System. — Very early in
development (Fig, 325) the keel
of the vertebrate embryo is laid
down as a groove or gutter in the
ectoderm of the blastodermic area
(Chap. XIX.). The walls of this
' medullary ' or ' neural ' groove
grow inwards, and at length there
is formed, by their coalescence, the ' neural canal ' (Fig. 326), which
expands at its anterior end to form four cerebral vesicles (Fig. 327).
Thus there is a continuous tunnel from
end to end of the primary cerebro-spinal
axis; and this persists as the central
canal of the spinal cord and the ven-
tricles of the brain, whose ciliated
epithelium represents the ectodermic
lining of the primitive neural canal. In
the adult portions of the canal may
become obliterated from an overgrowth
of the lining cells, and the cilia are, if
present at all, less distinct than in the
child, and far less distinct than in the
lower animals. From the wall of this
canal is formed the cerebro-spinal axis,
in which developing nerve-cells or neuro-
B
Fig. 327. — Diagram to illustrate
the Formation of the Cerebral
Vesicles. A. i indicates the
cavity of the secondary fore-
brain, which eventually becomes
the lateral ventricles. In B the
secondary fore-brain has grown
backwards so as to overlap the
other vesicles. I, first cerebral
vesicle (primary fore-brain or
'tween brain) ; II, second cerebral
vesicle (mid-brain); III, third
cerebral vesicle (hind-brain) ; IV,
fourth cerebral vesicle (after-
brain).
Fig. 326. — Neural Canal at a Later
Stage (Beard). C, neural canal;
G, posterior spinal ganglion.
blasts soon become differentiated from the supporting cells or spongio-
blasts, and wander outwards from the neighbourhood of the central canal
(Fig. 338) till their further progress is checked by the barrier of the mar-
54
85o THE CENTRAL NERVOUS SYSTEM
ginal veil, a closely-woven network or thicket, into which the processes of
the spongioblasts break up at the outside of the primitive cerebro-spinal
axis. Although the neuroblasts themselves are unable to penetrate
the marginal veil, the axis-cylinder processes of some of them do so,
and form the motor roots of the spinal nerves. The neuroblasts from
which the fibres of the white columns of the cord are developed are
apparently unable to send their axons through the marginal veil.
They are accordingly forced to assume a longitudinal direction, and
in this way the central grey matter becomes covered with a sheath of
longitudinal white fibres. For a time only motor nerve-cells and the
fibres connected with them are developed in the cerebro-spinal axis.
The ganglia on the posterior roots arise from a series of ectodermic
thickenings or sprouts from the neural crest which runs along the dorsal
aspect of the neural canal. These sprouts contain the neuroblasts
which develop into the spinal ganglion cells with the posterior root-
fibres. From each pole of each neuroblast a process grows out, one
towards the periphery, which forms a peripheral nerve-fibre, the other
centrally to connect the cell with the cord. From the after-brain (or
myelencephalon) is developed the medulla oblongata or spinal bulb,
from the hind-brain (or metencephalon) the cerebellum and pons,
from the mid-brain (or mesencephalon) the corpora quadrigemina and
crura cerebri. The fore-brain, or primary fore-brain (thalamencepha-
lon), gives rise of itself only to the third ventricle and optic thalamus;
but a secondary fore-brain (telencephalon) buds off from it and soon
divides into two chambers, from the roof of which the cerebral hemi-
spheres, and from the floor the corpora striata, are derived. Their
cavities persist as the lateral ventricles, which communicate with the
third ventricle by the foramen of Monro. The olfactory tracts are
formed as buds from the secondary fore-brain.
To complete the story of the development of the brain, it may be
added that the retina is really an expansion of its nervous substance.
A hollow process, the optic vesicle, buds out on each side from the
primary fore-brain. A button of ectoderm, which afterwards becomes
the lens, grows against the vesicle and indents it so that it becomes
cup-shaped, the inner concave surface of the cup representing the
retina proper, the outer convex surface the choroidal epithelium. The
stalk becomes the optic nerve.
Histological Elements of the Central Nervous System. — The central
nervous system is built up (i) of true nervous elements, (2) of sup-
porting tissue. The nervous elements have usually been described as
consisting of nerve-fibres and nerve-cells, but the antithesis of a time-
honoured distinction must not lead us to forget that the essential
part of a nerve-fibre, the axis-cylinder, is a process of a nerve-cell,
and the medullary sheath a structure whose integrity is intimately
related to that of the axis-cylinder.* In strictness, the term ' nerve-
cell ' ought to include not only the cell-body, but all its processes, out
to their last ramifications. But the habit of speaking of the position
of the ccll-bodyf as that of the nerve-cell is so ingrained, that it seems
better to continue the use of the latter term in its old signification, and
to speak of the cell and branches together as a neuron (also spelled
neurone).
* While the medullary sheath, like the axis-cylinder, seems to be as regards
its nutrition under the control of the nerve-cell, and must therefore be looked
upon as an integral portion of the neuron, although not essential for its de-
velopment, the neurilemma in respect both of its nutrition and its develop-
ment appears to be an independent structure.
f Foster and Sherrington call the cell-body the perikaryon.
HISTOLOGICAL ELEMENTS
851
The Neurons. — A typical nerve-cell (Figs. 328, 330, 332)15 a knot of
granular protoplasm, containing a large nucleus, inside of which lies
a highly refractive nucleolus. A centrosome and attraction sphere
(p. 5) have also been found in some nerve-cells, though not as yet
demonstrated in all. Pigment may also be present, especially in old
age. By certain methods of staining it may be shown that fibrils
(neuro-fibrils) run through the protoplasm of the cell, forming a felt-
work in it, and entering the dendrites on the one hand and the axis-
cylinder process on the other (Figs. 328, 331, 335). In the axis-
cylinders of nerve-fibres the fibrils (Fig. 329) appear to preserve their
identity down to the distribution of
the fibre. In the ground substance
between the fibrils lie round, an-
gular, or spindle-shaped bodies
(Nissl's bodies) which stain with
basic dyes (Fig. 340) . * These bodies
vary in appearance in different
kinds of nerve-cells, and in the
same nerve-cell under different con-
ditions. According to Macallum,
they contain organically combined
iron. In a multipolar cell, like those
Fig. 328. — Anterior Horn Cell from Man
showing Fibrils (Bethe).
Fig- 329. — Medullated Nerve-
Fibre showing Fibrils of Axis-
Cylinder (Bethe). The fibrils are
seen passing, without interrup-
tion, across a node of Ranvier.
in the anterior horn of the spinal cord, several processes — it may be five
or six, or even more — pass off from the cell-body (Frontispiece). The
most complete pictures of them are given by preparations impregnated
according to the method of Golgif (Figs. 330, 333). One of the pro-
* In Nissl's method the sections are stained in a solution of methylene blue,
and decolourized in anilin-alcohol.
f The method depends upon the deposition of mercury, or silver, in or
around the cell-bodies and their processes in tissues which have been hardened
in bichromate of potassium and then soaked in a solution of mercuric chloride
or silver nitrate. In Pal's improvement of Golgi's method a solution of sodic
sulphide follows the mercuric chloride.
852
THE CENTRAL NERVOUS SYSTEM
cesses of most nerve-cells is distinguished from the rest by the fact
that it maintains its original diameter for a comparatively great
distance from the cell, and gives off comparatively few branches.
This process, which in favourable preparations can be traced on till it
becomes the axis-cylinder of a nerve-fibre, is called the axis-cylinder
process, or more shortly the axon. The few slender brai ches that come
off from it, usually at right angles, are called collaterals. The collaterals
consist essentially of one or more fibrils of the axon. Both the main
thread of the axon and the collaterals end by breaking up into an
arborescent system of fibrils or telodendrion. The telodendrions vary
greatly in appearance from simple end -brushes to far-branching
thickets, or such special end-organs as motor plates (Fig. 335) or
muscular spindles. The rest of the processes of the cell, which are
termed dendrites or protoplasmic processes, very rapidly diminish in
diameter, as they pass away from the cell by breaking up into
Fig- 33O. — Multipolar Nerve-Cell: Golgi Preparation (Barker, after Kolliker).
», axon; c, collaterals.
fibrils like the branches of a tree. The Nissl bodies extend for some
distance into the dendrites, but not into the axon. The dendrites
of some cells, especially the pyramidal cells of the cerebral, and
the Purkinje's cells of the cerebellar cortex, have small swellings,
the so-called lateral buds or gemmules, on their course. Their signifi-
cance is unknown. The dendrites terminate at a little distance from
the cell, where they come into relation with the end -arborizations of
the axons of other neurons. In this way two or more neurons are
linked together to form a nervous path. According to the view most
commonly held (neuron hypothesis), the relation is not one of actual
anatomical continuity, but the processes come so close together that
nerve impulses are able to pass across from the terminal brush of the
axon of one nervous element to the dendrites or cell-body of another.
This kind of junction is called a synapse.
It has been suggested that the contact may be rendered more or less
close through amoeboid movements of the dendrites, and that in this
HISTOLOGICAL ELEMENTS
way the nervous impulse may be switched like a railway-train from
one path to another. But there is no experimental basis for this some-
what crude, if fascinating, hypothesis. Sherrington has suggested
that the presence of a ' membrane ' at the synapse may limit the con-
duction and determine its direction. Some membranes, such as frog's
skin, are known to possess a so-called irreciprocal permeability for
certain substances, permitting them to pass more easily in one direc-
tion than the other, and it is conceivable that a membrane at the
synapse might have a similar action in respect to the movement of ions
concerned in the propagation of the nervous excitation. Whatever
A.
Fig. 33I-— Nerve-Cells of Hirudo (Schafer,
after Apathy). A, unipolar motor cell;
a, network of neuro-fibrils near the sur-
face of the cell ; b, near the nucleus n ;
c, afferent, d, efferent neuro-fibril. B, bi-
polar sensory cell a with its nucleus n ;
cu, cuticle; ep, epidermis cells between
which a neuro-fibril passes up from its
branched ending near the surface of the
skin to the nerve-cell, where it forms a
network, which gives off a fibril passing
towards the central nervous system.
Fig. 332. — Large Pyramidal Cell of
Cerebral Cortex (Barker, after Bech-
terew). a, axon; b, dendrite.
the nature of the relation between two superposed neurons may be, it
does not permit the conduction of nerve-impulses indiscriminately in
both directions. For instance, stimulation of the central end of the
posterior root of a spinal nerve causes an electrical response (p. 824)
in the anterior root of the same segment, while no electrical change is
produced in the posterior root by stimulation of the anterior. We shall
see later on (p. 872) that some of the fibres of the posterior root and
their collaterals end by arborizing around the dendrites of the cells ot
the anterior horn. The excitation is, therefore, able to pass from the
854
THE CENTRAL NERVOUS SYSTEM
telodendrions of the posterior root-fibres through the dendrites of the
anterior horn cells towards their cell-bodies, but not in the opposite
Fig. 333. — * — e shows the development of the pyramidal nerve-cells of the cerebral
cortex in a typical mammal; a, neuroblast with commencing ax on; b, dendrites
appearing; d, commencing collaterals. A — D shows the different degree of com-
plexity in the fully-developed pyramidal cells in different vertebrates: A, frog;
B, lizard; C, rat; D, man (Donaldson, after Ram6n y Cajal).
direction, and in general the direction of conduction is from the den-
drites towards the cell-body.
Some investigators believe that the fibrils already spoken of as
forming a felt-work in the protoplasm of the nerve-cell may run right
Fig. 334. — Cells from the Gasserian Ganglion of a Developing Guinea-Pig.
originally bipolar cells are seen changing into cells apparently unipolar,
same process occurs in the cells of the spinal ganglia (Van Gehuchten).
The
The
through from one cell to another, thus constituting an actual anatomical
connection between the neurons, and that such a connection may be
established also by fibrils which do not enter the cells at all, but run in
the intercellular substance of the grey matter. Such a continuity of
HISTOLOGICAL ELEMENTS
fibrils from cell to cell has
been demonstrated in some
of the invertebrates — e.g.,
in annelids (Fig. 331) —
where previously the best
examples of strictly iso-
lated neurons were sup-
posed to be found (Apathy) .
The supporters of the
theory of continuity look
upon the cell-body as
merely necessary for the
nutrition of the nerve-net,
but deny that it is neces-
sary for the conduction of
nerve-impulses. If this is
the case, it is obvious that
the neurons can no longer
be considered as functional
units in which the law of
isolated conduction of
nerve-impulses (p. 793)
holds good. Nor is it by
any means so easy to un-
derstand as on the neuron
hypothesis such facts as the
strict limitation of Wal-
lerian degeneration to the
boundaries of the neurons
directly affected, or the
strict limitation of the
silver reduction in Golgi
preparations to single neu-
rons. It is, of course, true
that the simplicity and
order introduced by the
neuron hypothesis into our
conceptions of the nervous
conduction paths by no
means prove its accuracy.
Yet they are reasons for
not lightly abandoning it,
and it has recently been
corroborated by important
new evidence on the growth
of nerve-cells on artificial
media outside of the body
(p. 802; Fig. 337, p. 857).
Varieties of Neurons. —
Nearly all the nerve-cells
of the cerebrb-spinal axis
agree with the cells of the
anterior horn in the posses-
sion of an axon and one or
more dendrites, although
sometimes the dendrites
are scanty in number and
Fig. 335. — Scheme of Lower Motor Neuron
(Barker), a, h, axon-hillock (the portion of the
cell from which the axon comes off), containing
no Nissl bodies, and showing fibrillation; cue,
axis-cylinder or axon; m, medullary sheath,
outside of which is the neurilemma; c, cell-
substance (cytoplasm), showing Nissl bodies in
a lighter ground substance; d, protoplasmic
processes or dendrites containing Nissl bodies;
n, nucleus; »', nucleolus; n, R, node of Ranvier;
s,f, side fibril; n of n, nucleus of the neurilemma;
tel., motor end-plate; m', striped muscle-fibre;
s, L, incisure.
856
THE CENTRAL NERVOUS SYSTEM
insignificant in size. In the cerebral cortex the typical cells are oi
pyramidal shape. From the base comes off the axon, and from the
angles dendritic processes, a particularly massive dendrite proceeding
from the apex of the pyramid towards the surface of the brain.
Sometimes an axon, instead of ending in an arborization which
comes into relation with the dendrites of another nerve-cell, or, as is
more frequently the case, with the dendrites of more than one cell,
breaks up into a sort of basket-work of fibrils surrounding the cell-
body. The cells of Purkinje, for instance, in the cerebellum are sur-
rounded by such pericellular baskets (Fig., 336). The cells of the spinal
ganglia have two axons, which in the embryo arise one from each end
of the bipolar cell, but in the adult, in all vertebrates except some
fishes, are connected to the cell by a single process (Fig. 334)- It has
been commonly held that the unipolar cell with a single T-shaped
process is developed from a bipolar cell,
which grows towards one side, so that the
two processes come together and fuse.
Such observations as that of Harrison on
the bifurcation of the growing end of the
main process of isolated nerve-cells culti-
vated in vitro suggest an alternative and
a simpler explanation — viz., that the
T-shaped process is derived from the
splitting of a single chief process. If this
be the case, one of the original processes
at the poles probably undergoes a retarded
development or disappears, since the great
majority of the spinal ganglion cells with
the T-shaped process appear to have no
dendrites. Another kind of cell which
seems undoubtedly to be of nervous nature
is the ' granule-cell.' Granule-cells are
much smaller than the nerve-cells we have
been describing. Their processes are much
less easily followed, but all appear to give
off an axon and several dendrites. They
contain a relatively large nucleus (5 to 8 /j.
in diameter), with only a mere fringe of
cell-substance. The nucleus, unlike that
of a large nerve-cell, stains deeply with
hsematoxylin. Some parts of the grey
matter are crowded with these granule-cells — e.g., the nuclear layer
of the cerebellum and the substantia gelatinosa, or substance of
Rolando, which caps the posterior horn in the cord. In other parts
they are more thinly scattered, but probably they are as widely diffused
as the large nerve-cells proper, and no extensive area of the grey matter
is wholly without them.
Although there are several varieties of granules (Hill), they all
agree in this, that their axons run a comparatively short course, and
never, or rarely, pass beyond the grey matter. Another kind of neuron
which is also confined to the grey matter, and is typically seen in the
cortex of the cerebrum and cerebellum, presents the peculiarity of an
axon which branches into an intricate network immediately after
coming off from the cell (cell of Golgi's second type). Unlike the long
axon of the typical large nerve-cell, the axis-cylinder process of this
Golgi cell remains unmedullated.
The -sympathetic ganglion cells are developed from immature neuro-
Fig. 336. — Pericellular Baskets
(Schafer, after Cajal). Two
cells of Purkinje from the
cerebellum are seen sur-
rounded by end ramifications
forming a basket-work, b, de-
rived from the branching of
axons of small nerve-cells in
the molecular layer; a, axon.
HISTOLOGICAL ELEMENTS
857
blasts that migrate, in the course of development, from the rudiments
of the spinal ganglia, and gathering in clumps form the ganglia of the
sympathetic chain (His). They agree in general with the cells of the
cerebro-spinal axis in possessing an axon and one or more, commonly
several, dendrites, although a few of them are devoid of dendrites.
The great majority of the axons remain unmedullated, but a few
acquire a very fine medullary sheath.
The epithelium lining the central canal of the cord and the ventricles
of the brain has also been considered by some as of nervous nature.
The fact that the deep ends of the cells are continued into processes
which pierce far into the grey substance has been supposed to lend
weight to this opinion, but there is no good ground for it.
Growth of Neurons. — The growth of a neuron from origin to com-
pletion is a comparatively slow process in the higher animals. Early
in foetal life (about the third or fourth week in man) certain round
germinal cells make their appearance amid the columnar ectodermic
cells surrounding the neural canal. From their division are formed,
in the first months of embryonic life, the primitive nerve-cells or
neuroblasts. These soon elongate and push out processes, first the
Fig. 33,7.— Isolated nerve-cells from the spinal cord of a tadpole growing in clotted
Ivmph. A, B, C, are cells in different stages of growth. The lower view of C
was drawn under the microscope 4$ hours later than the upper (Harrison).
axon or axons, and then the dendrites (Fig. 333). The formation of
the axons from the nerve-cell is most clearly followed in isolated
cultures (Fig. 337). As development goes on, the cell-body grows
larger, and the processes longer and more richly branched. The axon
and its collaterals, when it has any, in the case of the great majority of
the nervous elements of the brain and cord, ultimately acquire a
medullary sheath, although, as we have said, the time at which medul-
lation is completed varies in different groups of elements, and in some
nervous tracts it is even wanting at birth. At birth, too, the branches
of many of the cells are less numerous, and the connections between
different nervous elements therefore less intimate than they will after-
wards become. For many years the processes, and particularly the
axons, continue not only to grow longer, but to grow thicker as well.
The cell-body also enlarges, and the quantity of material in it that
stains with basic dyes increases. In the growing (lumbar) spinal
ganglia of the white rat the increase in volume of the largest cell-
bodies is very closely correlated with the increase in area of the cross-
section of the nerve-fibres growing out of them. The cross-section
of the axis-cylinder is, and remains, almost exactly equal to the area
858
THE CENTRAL NERVOUS SYSTEM
of the medullary sheath (Donaldson). Even after puberty is reached
the anatomical organization of the nervous system may still continue
to advance, although at an ever-slackening rate, and the finishing
touches may only be given to its architecture in adult life. In old
age the nervous elements decay as the body does. The cell-
body diminishes in size; the stainable material lessens in amount;
vacuoles form in the protoplasm and pigment accumulates ; the nucleus
shrinks; the nucleolus is obscured or may disappear altogether. At
the same time the processes of the cell, and especially the dendrites,
tend to atrophy (Fig. 339).
Nutrition of the Neuron. — We have already seen that when an axon
is cut off from its cell-body, it and its medullary sheath, when it
possesses one, undergo a rapid degeneration. It was long supposed
Fig. 338. — Section
through Half of Neural
Tube (Barker, after
His). The pear-
shaped neuroblasts are
seen migrating out-
wards. The axons of
some of them are seen
pushing their way out
through the marginal
veil as the anterior
root of a spinal nerve.
Fig. 339. — i, spinal ganglion cells of a still-born male
child; 2, of a man ninety-two years old ( x 250)
— N, nuclei; 3, nerve-cells from the antennary
ganglion of a honey-bee just emerged in the per-
fect form; 4, of an old honey-bee. The nucleus is
black in the figure. In 3 it is very large, in 4 it
is shrunken and the cell-substance contains
vacuoles (Hodge).
that no change took place in the nerve-cell. The researches of recent
years have shown that not only does loss of the specific function and
trophic influence of the cell-body affect the nutrition of the axon, but
loss of function of the axon reacts on the cell-body. In many cases
at least, when a nerve-fibre is divided from its cell, characteristic
changes are produced in the latter and in its dendritic processes, and
they are scarcely less rapid, although usually less profound, and far
more transient than the degeneration in the peripheral portion of the
nerve-fibre. The cell-body and the nucleus swell. Many of the Nissl
bodies (Fig. 340) disintegrate, and are reduced to a finely granular
condition. After a time much of the disintegrated chromatic sub-
stance disappears altogether. The nucleus may be displaced to one
HISTOLOGICAL ELEMENTS
859
side of the cell. Certain changes in the neurofibrils of the cell may
accompany the changes in the chromatin. In rabbits after division
of the facial nerve the alterations in its nucleus of origin have been
found to reach a maximum in about three weeks, after which there is a
tendency to recovery on the part of the majority of the cells, even when
regeneration of the nerve has been prevented by cutting out a portion
of it. Some of the cells may completely atrophy and disappear.
Similar changes have been found by Warrington in the motor cells ol
the anterior horn after section of the posterior (dorsal) spinal roots.
Since in this case no anatomical injury has been inflicted on the motor
neurons, it has been surmised that the cause of the alterations is the
loss of impulses which normally reach them along their dendrites. In
short, we may say, with Marinesco, that the functional and anatomical
integrity of the neuron depends on the integrity of all its constituent
parts, and of the neurons which carry to it functional excitations — i.e.,
excitations connected with its proper physiological work. The neuron,
in fact, lives by its function, or, in common language, by doing its
work. Yet the anatomical tokens of mere disuse, as in the motor cells
Fig. 340. — Cells from the Nuclei of the Oculo-Motor Nerves of the Cat Thirteen Days
alter Division of the Root-Fibres on one Side: Nissl's Stain (Barker, after Flatau).
a, normal cell from side on which the roots were not cut ; b, cell from side operated
upon. Only a few Nissl bodies are present in b, and the nucleus is displaced to
one side of the cell.
of the anterior horn after division of the cord at a higher level, are less
distinct than those which follow section of the axon. Therefore it
must be concluded that the latter, although not indispensable for the
nutrition of the cell as the cell is for the axon, exerts an influence upon
it. Similar changes in the chromatin may also be produced in nerve-
cells by a period of anaemia, in extensive superficial burns, in tetanus
caused by the injection of bacterial cultures, in acute alcoholic poisoning,
in fatigue, and in other ways. According to Wright, the inhalation
of ether or chloroform (in dogs) so alters the chromatic substance
that it loses its affinity for aniline dyes. In long-continued anaesthesia
the nucleus is also affected, while the nucleolus is the last part of the
cell to suffer. A greater alteration occurs in the cells in the three hours
between the sixth and ninth hours of anaesthesia than in the five hours
between the first and sixth. Although the changes are transitory, the
cells, after a narcosis of nine hours, being practically normal in forty-
eight hours, they indicate that the duration of safe surgical anaesthesia
has a limit measured by hours.
It is probable that the alterations in the chromatic substance should
THE CENTRAL NERVOUS SYSTEM
not be looked upon as the token of any specific lesion; they are the
common structural response of the cell to injurious influences of the
most varied nature.
Grey and White Matter. — Nerve-cells are the most distinctive his-
tological feature of the grey nervous substance. Sown thickly in the
cerebral cortex, the basal ganglia, the floor of the fourth ventricle, and
the cervical and lumbar enlargements of the cord, they are scattered
more sparingly wherever the grey matter extends. They also occur
in the spinal ganglia, and their cerebral homologues (such as the Gas-
serian ganglion), in the ganglia of the sympathetic system, and the
sporadic ganglia in general. But wide as is their distribution, and
great as is the size of the individual cells, some of which have a diameter
of 140 //, or even more, they yet make up but a small portion of the whole
of the central nervous substance, the total weight of the 9,000 millions of
nerve-cell bodies in the human brain being less than 27 grammes
(Donaldson). And although it is not to be wondered at that objects
so notable when viewed under the microscope should have struck the
imagination of physiologists, it is probable
that the very high powers which it is so
common to attribute exclusively to them
are, in part at least, shared with the network
or feltwork formed by their processes.
The grey matter, in addition to this ex-
ceedingly delicate feltwork of non-medullated
fibres and filaments representing the den-
drites and such axons and collaterals as
terminate within itself, contains also, as may
be seen in preparations stained by Weigert's
method,* great numbers of exceedingly fine
medullated fibres, many of which are the
collaterals of fibres that are passing out to the
white matter.
Only medullated nerve-fibres are met with
in the white matter of the cerebro-spinal axis.
They are commonly stated to be devoid of a
neurilemma (or neurolemma), and in the sense
that there is no continuous separate mem-
branous sheath corresponding to the sheath
of Schwann of the peripheral medullated
fibres this is correct. Sheath cells, however,
are present, and form a reticulum around each fibre in the meshes
of which myelin is contained. In diameter the medullated fibres of
the white matter vary from 2 /* to 20 /*. In Malapterurus electricus
the fibre in the cord which supplies the electrical organ is of immense
size; and in the anterior column of many fishes may also be seen a
single gigantic fibre on each side with a diameter of nearly 100 ft. It
cannot be said that any relation between the functions of neurons
and the calibre of their axons has been definitely established. Many
afferent fibres, it is true, are small — this is notably the case with the
fibres of the posterior column, and many motor fibres are large. But
the distinction can by no means be generalized, for the fibres of the
direct cerebellar tract (p. 866), which certainly are afferent, are amongst
the largest in the spinal cord ; and the vaso-motor fibres, which pass from
the cord by the anterior (ventral) roots (Fig. 341) into the sympathetic,
are smaller than the fibres of the posterior column. Even the motor
* Weigert's is a special method of staining the medullary sheath with
haematoxylin.
Fig. 341. — Transverse Section
of a Bundle of Nerve-
Fibres from the Anterior
(Ventral) Root of the First
Coccygeal Nerve of the Cat
(Dale). The great differ-
ence in the diameter of the
fibres is well shown. The
small fibres are vaso-motor.
86 1
nerve-fibres of striated muscles vary considerably in diameter, those of
the tongue, e.g., being smaller than those of the muscles of the limbs.
Further, the medullated fibres of the brain are, without reference to
function, in general finer than the fibres of the cord. As a rule the
fibres whose course is the longest are the thickest, but the rule is often
broken. For example, the average diameter of the fibres going to the
thigh of the frog is greater than that of the fibres going to the lower
part of the limb (Dunn). The cause of these differences in the size of
nerve-fibres is quite unknown. It is more likely to be morphological
than physiological.
Supporting Tissue. — The protective membranes of the central nervous
system consist of ordinary connective tissue derived from the meso-
derm. The supporting framework which interpenetrates the nervous
substance consists of a peculiar form of tissue derived from the ecto-
derm, and called neuroglia. The whole cerebro-spinal axis is wrapped
in four concentric sheaths. Next the walls of the bony hollow in which
it lies is the dura mater. Next the nervous substance itself, following
the convolutions of the brain and the fissures of the cord, and giving
off bloodvessels to both, is the pia mater. Between the dura and
the pia, separated from the latter by a jacket of cerebro-spinal fluid,
is the double layer of the arachnoid. The comparatively coarse septa
that run into the nervous substance as if coming off from the pia mater
are the main beams in the scaffolding of non-nervous material with
which that substance is interwoven, and by which it is supported.
The interstices are filled in by a thick-set f eltwork of interlacing neurog-
lia fibres, which lie close against the small glia cells. In preparations
impregnated by the Golgi method many of the neuroglia fibres appear
to be processes running out from the attenuated cell-body like the
arms of a microscopic crab or spider. But this is a deceptive appear-
ance, as has been shown by means of special methods in which the
neuroglia fibres are alone stained (Weigert, Huber, etc.). They
generally lie in close contact with, or embedded in, the protoplasm
of the neuroglia cells, from which they have become differentiated
structurally and chemically, but sometimes they may detach themselves
entirely from the cells and lie free in the intervening tissue. The
neuroglia is present in greatest abundance in the grey matter immedi-
ately surrounding the central canal of the cord and the ventricles of
the brain (the ependyma, as it is called), from which long neuroglia
fibres pass out radially, giving off branches on their course, and ending
in little knobs or enlargements attached to the pia mater.
SECTION II.— GENERAL ARRANGEMENT OF THE GREY AND WHITE
MATTER IN THE CENTRAL NERVOUS SYSTEM.
(1) Around the central canal, as we have seen, a tube of grey
matter sheathed with white fibres is developed. This tube, from
optic thalamus to conus medullaris, may be conveniently referred to
as the central grey axis or stem, which, in the lowest vertebrates — e.g.,
fishes — is much the most important part of the central nervous
system.
(2) On the outer surface of the anterior portion of the neural
axis, but not in the part corresponding to the spinal cord, is laid
down a second sheet or mantle of cortical grey matter. Between
862 THE CENTRAL NERVOUS SYSTEM
this and the primitive grey stem are interposed (a) the sheath of
white fibres that clothes the latter, and connects its various parts,
and (b) a new development of white matter (corona radiata, cere-
bellar peduncles), which serves to bring the cortex into relation
with the primitive axis, and through it with the rest of the body.
Although there are histological and developmental differences
between the cerebral and the cerebellar cortex, we may, for some
purposes, classify them together as cortical formations. And we
may also include under this head the corpora striata, which, although
for descriptive purposes generally grouped with the optic thalami
and the other clumps of grey matter at the base of the brain, as the
basal ganglia, are to be regarded as cortical in character. As we
mount in the vertebrate scale the cortex formation of the secondary
fore-brain and hind-brain acquires prominence.
In other words, the grey matter developed in the roof of the cerebral
vesicles I. and III. (Fig. 327) (the grey matter of the cerebral and cere-
bellar cortex) comes to overshadow the superficial grey matter hitherto
present only in the roof of vesicle II. (in the corpora bigemina). And
this cortex formation becomes larger in amount, and, in the case of
the cerebral grey matter, more richly convoluted, the higher we ascend,
until it reaches its culmination in man. As the anterior cerebral
vesicles develop, they spread continually backward, until at length the
cerebral hemispheres cover over, and almost completely surround, the
primary fore-brain and the mid- and hind-brains, so that the anterior
portion of the primitive stem comes, as it were, to be invaginated into
the second wider tube of cortical grey matter. This development of
the cortical grey substance is accompanied with a corresponding
development of nerve-fibres, for an isolated nerve-cell (apart, of course,
from possible embryonic rudiments which have not undergone com-
plete development) is no more conceivable than a railway-station the
track from which leads nowhere in particular, or a harbour on the top
of a hill.
But it is to be particularly observed that the new formation does
not supplant the old, but works through and directs it. The neuro-
blasts of the cortex do not throw out their axons to make direct junc-
tion with muscles and sensory surfaces. Such junction the cortex
finds already established between the primitive cerebro -spinal axis and
the periphery. It joints itself on by nerve-fibres to the cells of the
central stem; and we have reason to believe that no single axon in an
ordinary spinal or cranial nerve* runs all the way from the periphery
to the cortex, and no axon of a cortical nerve-cell all the way from the
cortex to the periphery, but that the connection is made by a chain
of at least two neurons, the cell-body of one of which is situate in this
primitive grey tube.
The fibres from the cortex of each cerebral hemisphere (corona
radiata), radiating out like a fan below the grey matter, are gathered
together into a compact leash as they sweep down through the isthmus
of the brain in the internal capsule, to join the crura cerebri. The
cortex of each cerebellar hemisphere, and the ribbed pouch of grey
* The olfactory and possibly to some extent the optic nerves are exceptions
to this statement. Their relation to the cortex, as is easily understood from
the manner of their development (p. 850), is different from that of the other
nerves.
GREY AND WHITE MATTER IN THE SPINAL CORD 863
matter, known as the corpus dentatum, which is buried in its white
core, are also connected by strands of fibres with the central stem and
the cerebral mantle. The restiform body or inferior peduncle brings
the cerebellum into communication with the spinal cord. The superior
peduncle by one path, and the middle peduncle by another, connect it
with the cerebral cortex. A great transverse commissure, the corpus
callosum, unites the cerebral hemispheres across the middle line, while
transverse fibres, that break through the middle lobe or worm, form
a similar though far less massive junction between the two hemispheres
of the cerebellum.
The fibres of the nervous system may be divided into (i) fibres
connecting the peripheral organs with nerve-cells in the central grey
axis; (2) fibres connecting nerve-cells in this central axis with cells
in the external or cortical grey tube; and (3) fibres linking cortex
with cortex, or central ganglia with each other. In the third group
are included (a) fibres which connect portions of the cortex on the
same side (association fibres) ; (b) fibres which connect portions on
opposite sides of the middle line (commissural fibres) ; (c) fibres which
connect the central grey matter at different levels — e.g., the proprio-
spinal or endogenous fibres of the cord. Our first task is, therefore,
to trace the peripheral nerves to their cells of origin or centres of
reception* in the nervous stem. And although there is reason to
believe that the whole of the peripheral nerves, cerebral and spinal
(with the exception of the olfactory and optic, which are rather
portions of the brain than true peripheral nerves), form a morpho-
logical series, it will be well to begin with the spinal nerves, since
their motor and sensory fibres are gathered into different and definite
roots, whose course within the cord is, in general, more easily traced
than the course of the cerebral root-bundles within the brain.
SECTION III. — ARRANGEMENT OF THE GREY AND WHITE MATTER
IN THE SPINAL CORD.
The grey matter of the spinal cord is arranged on each side in a
great unbroken column of roughly crescentic section, joined with
its fellow across the middle line by a grey bar or bridge, which
springs from the convexity of the crescent, and is pierced from end
to end by the central canal. The anterior horn of the crescent,
although it varies in shape at different levels of the cord, is, in
general, broad and massive, in comparison with the slender and
tapering posterior horn. In the lower cervical and upper dorsal
region a moulding or projection, forming a lateral horn, springs
from the fluted outer side of the grey substance. Within the grey
matter nerve-cells are found, sometimes so regularly arranged that
they form veritable cellular or vesicular strands. Of these the best
* The centre or nucleus of reception of a nerve contains the nerve-cells
around which its axons terminate; the nucleus of origin of a nerve contains
the cells from which its axons arise.
864
THE CENTRAL NERVOUS SYSTEM
marked are — (i) The tract or tracts made up by the cells of the
anterior horn (Fig. 342), which practically run from end to end of the
cord, swell out in the cervical and lumbar enlargements, where the
cells are very numerous and of great size (70 jj, to 140 JJL in diameter),
and contract to a thin thread in the thoracic region, where they are
relatively few, scattered, and small. In the enlargements there
are several groups of these cells corresponding with the segments
of the limbs, the movements
of the hand, forearm, and
upper arm being each repre-
sented by a group in the
StillinGS Cervical cerv^ca^ an<^ those of the foot,
Nucleus leg> and tnigh by groups in
CeruLCaL *he lumbar swelling. In the
Enlargement
rll- Lateral &ft- column
(.column of- jfe infer-
txxt)
rest of the
well-marked
are present in
horn, a
cord only
groups of
two
cells
the anterior
mesial and a lateral.
Stilling's dorsal
nucleus or Clark's
Column
Cefls of 1tx. anterior
Cornu
-Scattered cells cf
intermedia-
tract
(2) Clarke's column, whose
cells, mostly of good size and
somewhat rounded in outline,
are situated at the inner side
of the root of the posterior
horn just where it joins on to
the grey cross-bar. It gradu-
ally increases in size from
above downwards, usually
appearing first at the level of
the seventh or eighth cervical
nerve, attaining its maximum
development at the eleventh
or twelfth dorsal and dis-
appearing altogether, as a
continuous strand, at the level
of the second or third lumbar
nerves. Scattered nerve-cells,
however, constituting the so-
called cervical and sacral nuclei of Stilling, are frequently found
occupying the same position towards the upper and lower ends of
the cord, and may be looked upon as isolated portions of Clarke's
column. (3) A tract of small cells calle4 the intermedia- lateral
tract, lateral cell column, or lateral Jiqrn* situated at the outer edge
of the grey matter, about midway between the anterior and pos-
terior horns. It is best marked in the thoracic region, up to about
the second thoracic segment, although jii the corresponding situa-
tion there are scattered cells in the lumbar swelling and the cervical
Sacral
Fig. 342. — Diagram of Grey Tracts of Cord.
GREY AND WHITE MATTER IN THE SPINAL CORD 863
cord. There is reason to believe that the axons of cells of the inter-
medio-lateral tract, which pass out as small medullated fibres in
the anterior roots, form the preganglionic segments of the efferent
vascular and visceral nerves (p. 185)- (4) The cells of the posterior
horn, which, although numerous, are smaller than those of the
anterior horn. Throughout the whole cord, however, two small
groups of cells may be distinguished, one on the lateral side of the
horn, about its middle, and the other on the mesial side, a little
in front of — i.e., ventral to — the edges of the substance of Rolando.
Both of these groups are broken up by the passage through them
of bundles of fibres which form a network, and they are therefore
called respectively the group of the lateral and the group of the
posterior reticular formation.
The white matter of the cord is anatomically divided by the
position of the nerve-roots and the anterior and posterior fissures
Fig. 343. — Diagrammatic Section of the Spinal Cord in the Cervical and Lumbar
Enlargements, to show Tracts of Fibres (Starr), i, antero-median column;
2, antero-lateral column; 3, ascending antero-lateral or Gowers' tract; 4, mar-
ginal tract (ground bundle, consisting of short endogenous fibres); 5, lateral or
crossed pyramidal tract; 6, direct cerebellar tract; 7, tract of Lissauer; 8, ex-
ternal portion, and 9, root zone, of Burdach's column; 10, comma tract; u, pos-
terior commissural tract; 12, Coil's column; 13, septo-marginal tract.
into three columns on each side: the anterior, lateral, and posterior
columns. The first two, since they are not separated by a perfectly
definite boundary, are often grouped together as the antero-lateral
column. In the cervical region it may be seen with the microscope
that the posterior white column is almost bisected by a septum
running in from the pia mater towards the grey commissure. The
inner half is called the postero-median column, or column of Goll;
the outer half the postero-external column, or column of Burdach
(Fig. 343). No localization of any of the other conducting paths
in the cord is possible by gross anatomical examination; but by
means of the developmental method and the method of degenera-
tion the columns of Goll and Burdach can be followed throughout
the cord, and several similar areas can be mapped out. We shall
only mention those that are physiologically the most important.
55
866 THE CENTRAL NERVOUS SYSTEM
When the spinal cord is divided, and the animal allowed to survive
for a time, certain tracts are picked out by the degeneration of their
fibres, although in every degenerated tract some fibres remain un-
affected. We may distinguish the tracts that degenerate above
the lesion (ascending degeneration) from those that degenerate
below the lesion (descending degeneration).
Ascending Tracts. — Above the lesion degeneration is found both
in the posterior and the antero-lateral columns. Immediately
above the section nearly the whole of the posterior column is in-
volved. Higher up the degeneration clears away from Burdach's
tract, and, shifting inwards, comes to occupy a position in the
column of Goll. In the antero-lateral column two degenerated
regions are seen, both at the surface of the cord, one a compact,
sickle-shaped area extending forwards from the neighbourhood of
the line of entrance of the posterior roots, and the other an area of
scattered degeneration, embracing many intact fibres, and complet-
ing the outer boundary of the column almost to the anterior median
fissure. The compact area is called the dorsal or direct cerebellar
tract, or tract ofFlechsig (or the fasciculus cerebello-spinalis),the diffuse
area the antero-lateral ascending tract, or tract of Gowers, or ventral
cerebellar tract (or the fasciculus antero-lateralis superficialis) .* The
dorsal cerebellar tract is distinguished by the large size of its fibres.
It is only distinct in the dorsal and cervical regions of the cord. The
tract of Lissauer, or posterior marginal zone, is another small ascend-
ing tract at the outer side of the tip of the posterior horn. It is
made up of fine fibres from the posterior roots which soon pass into
the posterior column.
Descending Tracts. — When the cord is divided, say, in the upper
dorsal or cervical region, the following tracts degenerate below the
lesion :
(1) A small group of fibres close to the antero-median fissure,
which has received the name of the direct pyramidal tract — pyramidal
because higher up in the medulla oblongata it forms part of the
pyramid ; direct, because it does not cross over at the decussation of
the pyramids, but continues down on the same side. In the stan-
dard anatomical nomenclature it is termed the fasciculus cerebro-
spinalis anterior. The direct pyramidal tract is only present in man
and the higher apes.
(2) A tract of degenerated fibres in the posterior part of the
lateral column. This is the lateral or crossed Pyramidal tract (or the
fasciculus cerebro-spinalis later alis),a.nd is muchlarger thanthedirect.
In the medulla it also lies within the pyramid, but, unlike the direct
pyramidal tract, it crosses to the opposite side of the cord at the
decussation. The pyramidal tracts are also called cortico- spinal to
indicate their origin and termination.
* Some writers employ the terms dorsal and ventral spino cerebellar
tracts.
GREY AND WHITE MATTER IN THE SPINAL CORD 867
D. C
(3) A tract of scattered degeneration lying along the margin of the
cord in the anterior portion of the antero-lateral column, and partly
overlapping the tract of Cowers. It is called the antero-lateral
descending tract, or tract of Loewenthal, or the vestibule- spinal tract.
(4) The prepyramidal (or rubro-spinal) tract, or Monakow's tract
(also called the fasciculus intermedio-lateralis) , lying immediately in
front of the crossed pyramidal tract.
(5) A small, comma-shaped island of degeneration (comma tract]
can be followed downwards for a short distance in the middle of
Burdach's column. It is only
seen in the cervical and
upper thoracic regions.
Less well known descending
tracts are —
(6) The olivo - spinal and
thalamico - spinal tracts (or
Helweg's bundle) in the anterc-
lateral column opposite the
head of the anterior horn.
This tract does not pass down
beyond the lower cervical re-
gion. The olivo-spinal tract
appears to consist of fibres
running down from the olivary
body into the cord, while the
thalamico-spinal tract is made
up of descending fibres origina-
t/ng in the oftic thala'mu,
This is an important tract in
the lower vertebrates, but not
in man.
(7) The tract of Marie in the
anterior column is chiefly a
continuation into the cord of
the posterior longitudinal bundle, one of the conspicuous tracts of the
brain-stem or upper portion of the cerebro-spinal axis (p. 885). It
contains both ascending and descending fibres.
When we have deducted the long ascending and descending tracts
which have been described, there still remains in the antero-lateral
column a balance of white matter unaccounted for. This white
substance, which does not degenerate for any great distance either
above or below a lesion, is called the antero-lateral ground-bundle,
and lies chiefly in the form of an incomplete ring around the grey
matter. For descriptive purposes it is sometimes distinguished as
the anterior ground-bundle (or fasciculus anterior proprius) in the
anterior column, and the lateral ground-bundle (or fasciculus later alts
proprius) in the lateral column. It is believed to consist of fibres
(endogenous or proprio-spinal fibres) which run only a comparatively
short course in the cord, and serve to connect nerve-cells at different
levels. Some of these endogenous fibres are ascending, others
V.B
Fi£- 344.-Scheme of Cross-Sectton of Spinal
ord (Donaldson, after Lenhossek). On the
right side DR> posterior (dorsal) root;
VR anterior (ventral) root; C.P., crossed
pyramidal fibres; C., direct cerebellar tract;
A.L., antero-lateral tract; B.C., posterior
columns.
868
THE CENTRAL NERVOUS SYSTEM
descending. The septo-marginal bundle consists also largely of fibres
which begin and end in the cord (proprio-spinal fibres) . Some endog-
Fig. 345 . — Medulla Oblongata, Pons and
Corpora Quadrigemina (Dorsal or Pos-
terior View) (Sappey). i, corpora
quadrigemina ; 2, nates; 3, testes;
4, anterior brachium uniting the nates
to the lateral geniculate body; 5, pos-
terior brachium uniting the testes to
the internal geniculate body 6 ; 7, pos-
terior commissure; 8, pineal gland
pulled forward to show nates; 9, su-
perior peduncle of the cerebellum ; 10,
ii, 12, valve of Vieussens; 13, troch-
lear nerve; 14, lateral sulcus; 15, fillet;
16, superior, 17, middle, and 18', in-
ferior, peduncle of the cerebellum;
19, floor of fourth ventricle; 20, audi-
tory nerve ; 21, spinal cord; 22, postero-
median column, continued hi the me-
dulla as the funiculus gracilis; 23, the
clava, the continuation of the funiculus
gracilis.
Fig. 346. — Medulla Oblongata, Pons
and Crura Cerebri (Ventral or An-
terior View). i, infundibulum ;
2. tuber cinereum; 3, corpus mam-
inillare; 4, cerebral peduncle or crus
cerebri; 5, pons; 6, middle peduncle
of cerebellum; 7, pyramid; 8, decus-
sation of pyramids; 9, olive; 10, tu-
bercle of Rolando ; n, external
arcuate fibres ; 12, upper end of cord ;
13, ligamentum denticulatum ; 14,
dura mater of cord; 15, optic tract;
16, chiasma; 17, third nerve; 18,
fourth nerve; 19, fifth nerve; 20,
sixth nerve; 21, seventh. nerve; 22.
eighth nerve; 23, nerve of Wrisberg
(portio intermedia), which unites
with the facial; 24, glosso-pharyn-
geal nerve; 25, vagus; 26, spinal
accessory; 27, hypoglossal; 28, 29,
30, first, second, and third pairs of
cervical spinal nerves.
enous fibres may also be intermingled with the fibres of certain of
the long tracts, both in the antero-lateraland posterior columns, and
GREY AND WHITE MATTER IN CEREBRO-SPINAL AXIS 869
Sherrington has shown (in the dog) that long proprio-spinal fibres
passing down in the lateral column connect the upper with the lower
parts of the cord (p. 908).
The next question which arises is: How are the long tracts con-
nected below — i.e., with the periphery — and above — i.e., with the
higher parts of the central nervous system ? The answer to this
question, partly derived from clinical records and partly from
experimental results, is in the case of some of the tracts unexpectedly
full and minute, though meagre in regard to others. But to render
it intelligible it is necessary, first of all, to describe briefly —
SECTION IV. — ARRANGEMENT OF GREY AND WHITE MATTER
IN THE UPPER PORTION OF THE CEREBRO-SPINAL Axis.
In the medulla oblongata the grey and white matter of the spinal
cord is rearranged, and, in addition, new strands of fibres and new
nuclei of grey substance make their appearance. Of these nuclei the
most conspicuous is the
dentate nucleus of the in-
ferior olive, whi ch , covered
by a crust of white fibres,
appears as a projection on j
the antero -lateral surface
of the medulla. In front
of the olive, between it
and the continuation of
the anterior median fis-
sure, is another projec-
tion, the pyramid, which
looks like a prolongation
of the anterior column of
the cord, but is made up
of very different consti-
tuents. Dorsal to the
olive is the restiform body
or inferior peduncle of the
cerebellum, and behind
the restiform body lie two Fig. 347 —Medulla Oblongata and Cerebellum, with
thin columns, the fumcu- Fourth Ventricle (Hirschfeld). i, mesial groove
his cuneatus, which con- of floor of ventricle running down to the calamus
tinues the postero-exter- scriptorius; 2, striae acusticae; 3, inferior peduncle
nal column of the cord, of the cerebellum; 4, clava; 5, superior peduncle
and thefuniculus gracilis, crossing the inferior and passing to its internal
which continues the pos- side; 7, 7. lateral sulcus; 8, corpora quadrigemina.
tero-internal column. In
these f uniculi are contained collections of small or medium-sized nerve-
cells termed respectively the nucleus cuneatus and the nucleus gracilis.
The rearrangement of the constituents of the cord is due mainly to two
causes: (i) The opening up of the central canal to form the fourth
ventricle, and the folding out, on either side, of the grey matter which
lies posterior to it in the cord; (2) the breaking up of the grey matter
of the anterior horn by strands of fibres as they sweep through it from
the lateral pyramidal tract to take up a position in the pyramid of the
opposite side (decussation of the pyramids), and a little higher up by
870 THE CENTRAL NERVOUS SYSTEM
fibres passing across the middle line from the gracile and cuneate nuclei
(sensory decussation or decussation of the fillet). The mosaic of grey
and white matter formed in the medulla by the interlacing of longi-
tudinal and transverse fibres with each other and with the relics of the
anterior horn, is called the reticular formation (formatio reticularis).
It occupies the anterior and lateral portions of the bulb behind the
pyramids and olivary bodies, and is continued upwards in the dorsal
portion of the pons and crura cerebri, and downwards for a little way
into the upper part of the cervical cord.
The cerebro-spinal axis passes up from the medulla through the pons,
encircled and traversed by the transverse pontine fibres derived from
the middle cerebellar peduncle or commissure, which enclose every-
where between them numerous collections of nerve-cells (nuclei pontis).
Enlarged by the accession of many of these fibres which come from the
cortex of the cerebellum on the opposite side, as well as of fibres from the
nuclei of the cranial nerves that take origin in this neighbourhood (fifth
and eighth), the central nervous stem bifurcates above the pons into the
two divergent crura cerebri. From each crus a great sheet of fibres
passes up between the optic thalamus and the caudate nucleus of the
corpus striatum on the one hand, and the globus pallidus of the lenticular
nucleus on the other, as the internal capsule, from which they are dis-
persed, in the corona radiata, to the cerebral cortex. Both in the upper
part of the pons and in the crus a ventral portion, or crusta, containing
the fibres of the pyramidal tract, and a dorsal portion, or tegmentum,
can be distinguished, the line of separation being marked in the crus by
a collection of grey matter, called^ from its usual, though not invariable,
colour the substantia nigra (Fig. 352). A portion of the tegmentum is
continued below the optic thalamus.
SECTION V. — CONNECTIONS OF THE LONG PATHS OF THE CORD.
Coming back now to our question as to the connections of the long
tracts of the cord, let us consider, first of all,
The Connections of the Postero-Median and Postero- External
Columns. — When a single posterior root is divided, say, in the dorsal
region, between the cord and the ganglion, its fibres, as we have
already seen (p. 797), degenerate above the section. Since the cell-
bodies of these neurons lie in the ganglion, if a series of microscopic
sections of the spinal cord be made, well-marked degeneration will
be found at the level of entrance of the root on the same side of the
cord, while below that level there will be only a few degenerated
fibres in the comma tract. Immediately above the plane of the
divided root the degeneration will be confined to Burdach's column
and to its external border. Higher up it will be found in the internal
portion of Burdach's and the external rim of Coil's column. Still
higher up the degenerated fibres will be confined to the postero-
median column ; the postero-external will be free from degeneration.
When a number of consecutive posterior roots are cut, the whole
of the postero-external column in the sections immediately above
the highest of the divided roots will be found occupied by degene-
rated fibres, while Coil's column may be free from degeneration, or
CONNECTIONS OF THE LONG PATHS OF THE CORD 871
degenerated only at its outer border. Higher up degeneration will
be found to have involved the whole of the postero-median column,
and to have cleared away altogether from the postero-external.
The degeneration in the column of Goll may be traced along the
whole length of the cord to the medulla, although the number of
degenerated fibres diminishes as we pass upward. The explanation
of these appearances 'is as follows : It may be
seen in preparations of the cord impregnated by
Golgi's method that the fibres of the posterior
roots soon after their entrance into the cord
divide into two processes, one of which runs up
and the other down in the posterior column, or
in the adjoining portion of the posterior horn.
From both of these collaterals are given off at
intervals to the grey matter. The descending
branches run downwards only for a short dis-
tance, and the degeneration in the comma tract
seen after section
of the cord is due
to the division of
these branches.
Many of the as-
cending branches
pass up for a short
distance in the
postero-external
column, sweeping
obliquely through
it to gain the tract
of Goll. In this
tract some of them
run right on to
the medulla ob-
longata, to end by
arborizing among
the cells of the
nucleus gracilis.
Other fibres, both
of Coil's and of
Burdach's tract,
end at various
levels in the cord,
their collaterals, and ultimately the main branches themselves,
coming into relation with nerve-cells in the grey matter. When the
cervical posterior roots are cut, many of the degenerated fibres
remain in Burdach's column up to the medulla, where they terminate
Fig. 348. — Diagrams
of Degeneration at
Different Levels in
the Cord after Sec-
tion of a Number of
Posterior Roots of
Nerves forming the
Lumbo-Sacral Plex-
us (Mott).
Fig. 349. — Branching of Posterior
Root-Fibres in Cord (Donald-
son, after Cajal). Collaterals,
Col, are seen coming off from
the two main branches of the
root-fibres, DR, and ending in
arborizations. CC, cells in the
grey matter of the cord, whose
axons also give off collaterals.
872 THE CENTRAL NERVOUS SYSTEM
in the nucleus cuneatus. In the posterior column, then, the
numerous fibres of the posterior roots which do not end in the spinal
cord are arranged in layers, the fibres from the lower roots being
nearest the median fissure (in the postero-median column), and those
from the higher roots farthest away from it (in the postero-external
column. Thus, in a section through the upper cervical region Goll's
column is almost entirely composed of fibres from the posterior limb,
while the column of Burdach consists of fibres from the anterior
limb. Other collaterals from the posterior root-fibres, and many
of the main root-fibres themselves, run into the anterior horn and
terminate in arborizations around its cells; some pass into the
posterior horn, and doubtless come into relation with its scattered
cells and, in the dorsal region, with the cells of Clarke's column.
Some of the posterior root-fibres and their collaterals also form
synapses with the cells of the intermedio-lateral tract. Other
collaterals and probably some axons cross the middle line in the
anterior and posterior commissures and end.in the grey matter of the
opposite side.
Connections of the Direct or Dorsal Cerebellar Tract. — Since the
dorsal or direct cerebellar tract does not degenerate after section of
the posterior nerve-roots, but does degenerate above the level of the
lesion after section of the spinal cord, the nerve-cells from which its
axons arise must be situated somewhere or other in the cord. Now,
it has been observed that the vesicular column of Clarke first becomes
prominent in the lower dorsal region, and that in this same region
the direct cerebellar tract begins. Atrophy of the cells of Clarke's
column has sometimes in disease been shown to accompany de-
generation of the direct cerebellar fibres. After an experimental
lesion of these fibres in animals, some of the cells of the vesicular
column show the changes in the Nissl bodies and the other changes
which we have already described as occurring in nerve-cells whose
axons have been cut. After two or three months these cells may
be found almost completely atrophied (Schafer). Finally, axis-
cylinder processes have been seen sweeping out from Clarke's
column into the direct cerebellar tract (Mott). The evidence, then,
is complete that the cells of origin of this tract are in Clarke's column.
Clarke's cells are surrounded by arborizations, some of which, as
previously stated, represent the terminations of posterior root-fibres
and of their collaterals. The neurons whose axons run in the dorsal
cerebellar tract are therefore the second link in an afferent path.
The direct cerebellar tract runs right up to the cerebellum through
the restiform body, without crossing and without being further
interrupted by nerve-cells. The restiform body ends partly in the
dentate nucleus of the cerebellum, partly in the vermis, and among
the fibres which end in the vermis are those of the direct cerebellar
tract. In the dorsal cerebellar tract there is a definite stratification
CONNECTIONS OF THE LONG PATHS OF THE CORD
8/3
of the fibres: the fibres from the lowest segments of the cord lie
outermost ; beneath these come fibres from the lowest thoracic, seg-
ments, then fibres from the higher thoracic segments; and, internal
to all, fibres from the topmost thoracic and lowest cervical segments.
Connections of the Antero-Lateral Ascending Tract. — According to
Schafer, the axons of this tract are probably connected "with cells
situated in the middle and posterior parts of the grey crescent, mainly
nX'
.p.m.f. ff ».y f.c.
n.ZT.
c.c.
u.m.f.
Fig. 350. — Transverse Section of Medulla
Oblongata at the Level of the Decussa-
tion of the Fillet (Halliburton, after
Schwalbe). a.m.f, anterior, and p.m.f,
posterior, median fissure; f.a and /.a2,
external arcuate fibres; f.a', internal
arcuate fibres becoming external; n.a.r,
nuclei of arcuate fibres; py, pyramid;
o, o', lower end of nucleus of olive ; f.r,
formatio reticularis; n.l, lateral nucleus;
n.g, nucleus gracilis; f.g, funiculus gra-
cilis; n.c, nucleus cuneatus; n.c', external
cuneate nucleus ; f.c, funiculus cuneatus;
g, substance of Rolando; c.c, central canal
surrounded by grey matter ; n. XI, nucleus
of spinal accessory; n.XII, of hypoglos-
sal; a.V, ascending root of fifth nerve;
s.d, the decussation of the fillet, or
superior decussation.
i§>- 35i — Transverse Section of Medulla
Oblongata at about the Middle of the
Olive (Schwalbe). f.l.a, anterior median
fissure; n.a.r, arcuate nucleus; £., pyra-
mid; n.XII, hypoglossal nucleus; XII,
root bundle of hypoglossal nerve coming
off from the surface ; at b it runs between
the pyramid and the dentate nucleus of
the olive, o; f.a.e, external arcuate fibres;
n.l, lateral nucleus; a, arcuate fibres going
to restiform body c.r, partly through the
substantia gelatinosa g, partly superficial
to the ascending root of the fifth nerve
a.V; X, root-bundle of vagus; h.X, n.X',
two portions of vagus nucleus; f.r, for-
matio reticularis; n.g, nucleus gracilis;
n.c, nucleus cuneatus; n.t, nucleus of the
funiculus ter'es;'».am, nucleus ambiguus;
r, rap he; o', o", accessory olivary nucleus;
p.o.l, peduncle of the olive.
on the opposite side of the cord, although also on the same side. None of
the fibres of the tract can come directly from the posterior nerve-roots,
since no degeneration is seen in it on section of the roots alone.
The antero-lateral ascending tract passes up through the medulla,
where some of its fibres perhaps form synapses with the cells of the
874
THE CENTRAL NERVOUS SYSTEM
lateral nucleus, a collection of grey matter in the lateral portion of the
spinal bulb. But its main strand runs on unbroken through the
medulla, in front of the restiform body, and behind the olive, and after
reaching the upper part of the pons bends back over and in company
with the superior peduncle as the ventral spino-cerebellar bundle, to
end in the worm of the cerebellum (Fig. 363).
A few fibres of Gowers' tract may pass by the middle peduncle to the
opposite cerebellar hemisphere. Some of its fibres do not go to the
cerebellum at all. One group can be followed to the corpora quadri-
gemina (spino-tectal fibres], and another by way of the tegmentumof the
cms cerebrt to the optic thalamus (spino-thalamic fibres) .
Through the relay of the gracile and cuneate nuclei, the postero-
internal and postero-external columns of the cord are further con-
nected on the one hand with the cerebrum, and on the other with the
cerebellum. The cells of the nuclei give off fibres (internal arcuate
fibres) which, sweeping in wide arches across the mesial raphe to the
opposite side, take up
a position behind the
pyramid in the tract of
the fillet, a bundle of
fibres which becomes
more compact, and
therefore more distinct,
as it passes brainwards.
Receiving fibres from
other sources on its
way, and also giving
off fibres, it runs up-
wards through the dor-
sal or tegmental portion
of the pons. In the mid-
brain it divides into
two portions, the lateral
fillet, also called the
lower fillet or fillet of Reil, and the intermediate, also called the upper
fillet. The lateral fillet contains mainly fibres arising in the cochlear
nucleus of the auditory never, and ends in grey matter of the pos-
terior corpus quadrigeminum, and partly in the mesial geniculate
body. It appears to be a path for the conduction of auditory
impulses. The intermediate fillet contains chiefly the fibres that
come off from the gracile and cuneate nuclei, but is enlarged by the
accession of fibres from the sensory nuclei of the cranial nerves. It
terminates in the lateral nucleus of the optic thalamus by forming
synapses with nerve-cells, whose axons, passing through the posterior
limb of the internal capsule and the corona radiata, continue the
afferent path to the cerebral cortex.
Not all of the axons from the cells of the cranial sensory nuclei run
Fig. 352. — Diagrammatic Transverse Section of
Crura Cerebri and Aqueduct of Sylvius, a, an-
terior corpora quadrigemina 6, aqueduct; c, red
nucleus; d, fillet; e, substantia nigra;/, pyramidal
tract in the crusta of the crura cerebri; g, fibres
from frontal lobe of cerebrum; h, fibres from tern-
poro-occipital lobe ; i, posterior longitudinal bundle.
CONNECTIONS OF THE LONG PATHS OF THE CORD 875
in the fillet. Many of them occupy a position in the reticular forma-
tion of the tegmentum dorsal to the fillet as they pass through the
pons and mid-brain to end in the thalamus and the region below it
(sub-thalamic region). From the sensory nucleus of the fifth nerve
a separate bundle of fibres ascends to the thalamus, in the tegmen-
tum of the mid-brain lateral to the posterior longitudinal bundle.
Connections of the Pyramidal Tracts. — When the cortex in and in
front of the fissure of Rolando is destroyed by disease in man, or
removed by operation in animals, it is found that in a short time
degeneration has taken place in the fibres of the corona radiata which
pass off from this area. The degeneration can be followed down
through the genu and the anterior two-thirds of the posterior limb
of the internal capsule
(Fig- 353) and the
crusta of the cerebral
peduncle of the corre-
sponding side into the
medulla oblongata.
Below the decussation
of the pyramids it is
found that the degene-
ration has involved the
two pyramidal tracts, V ™- ^V/ )&\a£f
and only these — the INTERNAL
crossed pyramidal
tract on the side oppo-
site the cortical lesion,
the direct pyramidal
tract on the same side
— and that the cross-
section of the two de-
generated tracts goes
on continually dimin-
ishing as we pass down the cord. (We overlook for the moment, in
the interest of simplicity of statement, the fact that some degenerated
fibres are found in the crossed pyramidal tract on the same side as the
lesion.) This is proof positive that the cell-bodies of the neurons whose
axons run in these tracts are situated in the cerebral cortex. They
have indeed been identified with certain of the large pyramidal cells
(the so-called giant cells or cells of Betz) in the cortex of the ' motor '
region in front of the Rolandic fissure (p 950). For after division
of the motor pyramidal fibres in the upper cervical region of the cord
(in monkeys) changes in the chromatin (so-called chromatolysis) and
atrophy of these large cells occur. The same has been found to be
true in man in cases where the cord was injured by fracture of the
spine in such a way as to interrupt the tract (as well as other tracts)
MID. BRAIN
Fig. 353. — Pyramidal Path (after Cowers). Degenera-
tion after destruction of the ' motor ' area of the
right cerebral hemisphere. The degenerated areas
are indicated by the shading.
876 THE CENTRAL NERVOUS SYSTEM
completely and permanently, without entailing death for a consider-
able time (Holmes and May). The fact that after destruction of the
cortex or the path in its course the degeneration below the lesion does
not spread to the anterior roots shows that at least one relay of
nerve-cells intervenes between the pyramidal fibres and the root-
fibres. The results both of normal and morbid histology enable us
to identify the cells of the anterior horn as the cells of origin of the
axons of the anterior root-fibres. For
(i) Axis-cylinder processes have been actually observed passing out
from certain of the so-called, motor cells of the anterior horn to become
the axis-cylinders of the anterior root.
(2). In the pathological condition known as anterior poliomyelitis,
the cells of the anterior horn degenerate, and so do the anterior roots
of the affected region, the motor fibres of the spinal nerves, and the
muscles supplied by them.
(3) As already mentioned (p. 858), comparatively transient but
decided changes occur in the anterior horn cells on section of the corre-
sponding anterior roots.
(4) An enumeration* has been made in a small animal (frog) of the
cells of the anterior horn and of the anterior root-fibres, and it has been
found that the numbers agree in a remarkable manner. From all this
it cannot be doubted that most, at any rate, of the cells of the anterior
horn are connected with fibres of the anterior root. But since the
number of fibres in the pyramidal tracts (about 80,006 in each half of
the human cord) falls far short of the number of fibres in the anterior
roots (not less than 200,000 in man on each side), it is necessary to
suppose either that one pyramidal fibre may be connected with several
cells or that all the anterior root-fibres are not in functional connection
with the pyramidal tract.
There is no reason to assume any such connection in the case of the
fine medullated root-fibres arising in the lateral liorn and going to the
visceral and vascular muscles.
While there is no doubt that anterior root-fibres and pyramidal
fibres of the brain and cord form segments of the same nervous path,
the connection between the pyramidal fibres and the cells of the
anterior horn has not yet been anatomically demonstrated. Many of
the pyramidal fibres pass into the grey matter between the anterior
and posterior horns or near the base of the posterior horn. The
anterior horn cells are surrounded by arborizations. Some of these
are probably the terminations of axons whose cell-bodies are situated
in the posterior horn, others the terminations of posterior root-fibres
or their collaterals. Many of them very likely represent the end
arborizations of pyramidal fibres or their collaterals. Some ob-
servers, however, suppose that the pyramidal fibres do not come into
immediate relation with the anterior horn cells, but that another
neuron is intercalated between them and the cells.
The pyramidal fibres are unquestionably paths for voluntary
motor impulses passing down from the cortex to the cord. But
* Such enumerations can be made with great accuracy from photographs
of sections of the nerves (Hardesty, Dale). (See Fig. 341, p. 860.)
CONNECTIONS OF THE LONG PATHS OF THE CORD 877
they are not the only cortico-spinal efferent paths, and in many
animals they are not even the most important paths for voluntary
movements. It is the more skilled and delicate movements which
the pyramidal tract subserves in man, and it is' these movements
which are permanently lost when the tract is destroyed. The size
of the path is proportioned to the degree of development of the
brain. Thus, it is larger in the monkey than in the dog, larger in the
anthropoid apes than in the lower monkeys, and larger in man than
Fig. 354. — Paths from Cortex in Corona Radiata (Starr). A, tract from frontal con
volutions to nuclei of pons and so to cerebellum; B, motor pyramidal tract;
C, afferent tract for tactile sensations (represented in the diagram as separated
from B by an interval for the sake of clearness); D, visual tract; E, auditory
tract; F, G, H, superior, middle, and inferior cerebellar peduncles; J, fibres
from the auditory nucleus to the posterior corpus quadrigeminum ; K, decussa-
tion of the pyramids in the bulb; FV, fourth ventricle. The roman numerals
indicate the cranial nerves.
in even the highest of the apes. In the lower mammals it is exceed-
ingly small. While in man the pyramidal tracts constitute nearly
12 per cent, of the total cross-section of the cord, they make up
little more than i per cent, in the mouse, 3 per cent, in the
guinea-pig, 5 per cent, in the rabbit, and nearly 8 per cent, in the cat.
In some mammals, as the rat, mouse, guinea-pig, and squirrel, the
pyramidal tracts lie, not in the antero-lateral, but in the posterior
columns. In vertebrates below the mammals the pyramidal system
does not exist as a collection of neurons which send their axons with-
878
THE CENTRAL NERVOUS SYSTEM
out interruption down from the cortex to the cord. In birds, e.g.,
after the removal of a hemisphere, the degeneration does not extend
below the mid-brain (Boyce).
SECTION VI. — PATHS FROM AND TO THE CORTEX.
Thus far we have been able to map out two great paths from
the cerebral cortex to the periphery — one efferent, the other afferent,
(i) The great efferent or motor pyramidal path, which, starting in
the cortex in front of the fissure of Rolando, where its axons give off
numerous collaterals to the grey matter soon after emerging from
the cells, and sweeping down the broad fan of the corona radiata,
passes through the narrow
isthmus of the internal cap-
sule into the crusta of the
crus cerebri, and thence into
the pons (Figs. 354, 355). At
this level, the fibres destined
to make connection with the
motor nuclei of the cranial
nerves in the grey matter
underlying the aqueduct of
Sylvius and the fourth ven-
tricle terminate. Most of
these fibres decussate to make
physiological connection with
nuclei on the opposite side,
but some join nuclei on the
same side. The question
whether they arborize di-
rectly around the cells of the
motor nuclei or make junc-
Fig. 355. — Motor Pyramidal Tracts (Diagram-
matic) (Halliburton, after Gowers). The
convolutions are supposed to be cut in
vertical transverse section, the internal
capsule, I, C, and the crus in horizontal
section. O, TH, optic thalamus; CN, cau-
date nucleus; L2 and Lj, middle and ex-
ternal portions of lenticular nucleus; /, a, I,
fibres from the face, arm, and leg areas of
the cortex respectively; E, S, Sylvian fis-
sure. The genu or knee of the internal
capsule is indicated by the asterisk.
tion with them through
another intercalated neuron
is precisely in the same
position as the corresponding
question for the spinal pyra-
midal path (p. 876). On their
way through the pons they send off collaterals to the nuclei
pontis, as they do higher up to the grey matter of the basal
ganglia of the cerebrum and the substantia nigra, and the path
may be continued to the motor nuclei by axons arising here.
There is no proof, however, that this is the case. The rest of
the pyramidal fibres run on into the pyramid of the bulb,
where the greater part (usually about 90 per cent.) of the fibres
decussate, appearing in the cervical cord as the massive crossed
PATHS. FROM AND TO THE CORTEX
879
pyramidal tract of the opposite side. A few (usually about 10 per
cent.) remain on the same side as the slender direct pyramidal tract.
The size of this tract varies much in different individuals, and it
is occasionally absent. Its breadth constantly diminishes as it
proceeds down the cord, and it disappears before the middle of the
thoracic region is reached, its fibres continually decussating across
the anterior white commissure and plunging into the opposite
anterior horn. They
either end among its
cells, or, passing through
it, reinforce the crossed
pyramidal tract. The
fibresof thiscrossedtract
A _
'-F
IS
tf^E
are, in their turn, con-
tinually passing off into
the grey matter to make
connection (p. 876) with
the cells of the anterior
horn, whose axis-cylin-
der processes enter the
anterior roots of the
spinal nerves. The losses
which it suffers as it
descends the cord may
be in some slight degree
compensated by the bi-
furcation of some of its
fibres (geminal fibres),
but ultimately the whole
tract forms synapses
with cells in the grey
matter, and dwindles
awav as the lumbar re- FiS- 356.— Horizontal Section through the Right
J. , , /T^. Hemisphere to show the Constituents of the
glonisreached(Flg-343). internal Capsule (von Monakow). A, knee of
A certain number of the corpus callosum ; B, anterior, B', posterior, horn of
Calc.
T'
pyramidal fibres do not
decussate either in the
bulb or in the cord.
These are called homo-
lateral fibres. They run
down in the lateral py-
ramidal tract, and are
represented by the fibres
that degenerate in that
tract after a lesion in the
lateral ventricle; C, knee of internal capsule;
S, sensory fibres; V, visual tract; AH, Amraon's
horn; Calc, calcarine fissure; T, first, T', second,
temporal convolution; OR, optic radiation; Aud,
auditory tract ; D, retrolenticular region of internal
capsule; lo, lenticulo-optic division of internal
capsule; Cl, claustrum; op., operculum; I, island
of Reil ; E, external capsule ; Is, lenticulo-striate
division of internal capsule ; F, fibres from frontal
lobe; F', inferior part of third frontal convolution;
Th, optic thalamus; Put, putamen.
motor ' area of the same side (p. 875).
This would explain the escape in hemiplegia (paralysis of one side
88o
THE CENTRAL NERVOUS SYSTEM
Thalamo-Corfital FibrfS
/sense of position \
\ • •• movement/
5(>ino-Cerebe!Ur
Tracts
/Co- ordination &•]
\ Muscular Tone I
.Crossed Sensory Fibres
/PW Hci,t& Cold\
llouch & Pressure/
ioAl Nerve -'^
Fig. 357. — Ascending Nerve Tracts (after Holmes).
PATHS FkOM AND TO THE CORTEX 881
of the body) of those muscles which are accustomed to work with
the corresponding muscles on the opposite side — e.g., the respiratory
muscles, these being innervated to some extent from both cerebral
hemispheres.
(2) A great afferent or sensory path by which some at least of the
impulses carried up through the posterior roots of the spinal nerves,
after passing through various relays of nerve-cells, reach the cortex
of the cerebellum ; or the upper portions of the central grey tube, the
corpora quadrigemina and optic thalamus; or, finally (through the
tegmentum and the posterior limb of the internal capsule behind the
motor fibres), the cerebral cortex itself.
The efferent pyramidal path from the cortex to the periphery is
broken by at most two relays of nerve-cells — those intercalated cells
to which reference has already been made (p. 876), if they really
exist, and the motor cells of the anterior horn. The afferent path to
the cerebral cortex is interrupted by at least three relays with axons
of considerable length. One of the cells is situated in the ganglion
on the posterior root, another in the medulla oblongata, a third in the
optic thalamus ; and on some of the routes another, or even more than
one, is intercalated between the medulla and the cortex (Fig. 357).
The Internal Capsule. — We have already recognized the pyramidal
tract and the afferent tegmental path as constituents of the internal
capsule. The cranial fibres of the pyramidal tract occupy mainly
the genu or knee, the spinal fibres the posterior limb as far back as
the posterior border of the lenticular nucleus (Fig. 356).
The fibres from the various motor areas are to a certain extent
arranged in order in the capsule, those for the eyes and head lying
farthest forward, those for the leg farthest back, while the fibres
going to the face, arm and trunk occupy intermediate positions.
The separation, however, is far from complete, the fibres of neigh-
bouring regions being considerably intermixed (Hoche). As the
tracts pass downwards the intermingling becomes continually
greater (Simpson and Jolly) (Figs. 358, 359)- The afferent fibres
from the thalamus to the cortex, which we have described as the
last segment of the afferent tegmental path, lie in the posterior part
of the posterior limb. But here again there is no absolutely sharp
line of demarcation. Some motor fibres are intermingled with the
sensory in the posterior part of the capsule, for lesions of this region
produce a certain degree of paralysis as well as anaesthesia on the
opposite side of the body. A pure capsular hemianaesthesia — that
is, a loss of sensation on the opposite side due to a lesion in the
internal capsule and unaccompanied by motor defect — does not
appear to exist. Accordingly the common statement that the efferent
(motor) path occupies the anterior two-thirds, and the afferent
(sensory) path the posterior third of the posterior limb of the
internal capsule, while true in a general sense, is not strictly correct,
56
882
THE CENTRAL NERVOUS SYSTEM
The destination of the afferent fibres of the internal capsule has
not been definitely settled. There is no doubt that they pass up to
the convolutions around the fissure of Rolando (central convolu-
tions), and there is reason to believe that some of them terminate in
the ' motor ' region in front of that fissure, although many of the
fibres concerned in tactile sensations seem to end in the ascending
parietal convolution.
But we have not yet exhausted the constituents of the internal
capsule. Two great cones of fibres
sweep down into it, one from the
frontal, the other from the occipital
and temporal portions of the cerebral
cortex. The first passes through its
anterior limb, the second behind the
sensory path in its posterior limb.
The cells of origin of the frontal fibres
are known, and those of the occipital
and temporal fibres are supposed, to
be situated in the cortex. They are
therefore efferent fibres as regards
the cortex (cortifugal). Running on
through the crusta of the cerebral
peduncle (Fig. 352), the frontal tract
Fig. 358.— Pyramidal Tract in In-
ternal Capsule (Simpson and
Jolly). Horizontal section
through right cerebral hemi-
sphere, cutting fibres of internal
capsule transversely at an upper
level a little below the upper
surface of the lenticular nucleus.
The extent of the degeneration
following destruction of the
whole of the right ' motor ' cor-
tex, except the ' head and eyes '
area (in one of the lower mon-
keys), is shown. Note over-
lapping of fibres from face, arm,
and leg areas, as shown by ex-
periments in which one or other
of these areas was alone re-
moved.
Fig- 359- — Pyramidal Tract in Internal
Capsule at Lower Level (Simpson and
Jolly). CN, head of caudate nucleus;
OT, optic thalamus; Cl, claustrum.
internal, the occipito-temporal external, they end in the grey
matter of the pons, and serve as one segment of an extensive
connection between the cerebral and the cerebellar cortex of the
opposite side, the other segment being formed by neurons whose
cell-bodies are situated in the pons, and whose axons, crossing
PATHS FROM AND TO THE CORTEX
883
the middle line, pursue their course through the middle cerebellar
peduncle, to terminate in the superficial grey matter of the cere-
bellum. It is evident that the junction of the cerebral cortex with
this pontine grey matter, through and into which so many nerve-
tracts pass, multiplies the number of possible routes by which
impulses may travel between one part of the brain and another.
The corpus callosum forms a mighty link between the two cerebral
hemispheres. And intertwined in the corona radiata with the
callosal fibres are other systems, of which it is especially necessary
to mention the afferent (cortipetal) fibres that join the optic thalamus
with nearly every part of the cerebral cortex. Such fibres pass from
the cells of the grey matter of the thalamus to the frontal and parietal
Fig. 360. — Association Fibres (after Starr). Cerebral hemisphere seen from the side
A, A, association fibres between adjacent convolutions; B, between frontal and
occipital lobes; C, cingulum, connecting frontal and temporo-sphenoidal lobes;
D, uncinate fasciculus between frontal and temporal regions; E, inferior longi-
tudinal bundle between occipital and temporo-sphenoidal lobes; O.T., optic
thalamus; C.N., caudate nucleus.
regions through the anterior border of the internal capsule in front of
the frontal fibres previously described as running in the anterior
limb of the capsule to the pons; and from the thalamus to the occi-
pital region through the extreme posterior border of the internal
capsule, behind the occipital fibres that proceed to the pons. The
fibres that connect the thalamus with the occipital cortex are
spoken of as the optic radiation. Some of the fibres of the optic
radiation, however, proceed, not from the thalamus, but from the
anterior corpus quadrigeminum and the lateral geniculate body.
The thalamus is also connected with the cortex of the temporal lobe,
with the cerebellum, and through the fillet with the posterior part of
the tegmental system, the medulla cblongata and the spinal cord
(p. 874). Fibres also pass from the inner and deeper part of the
thalamus to the lenticular nucleus of the corpus striatum. The
884
THE CENTRAL NERVOUS SYSTEM
thalamus mast be regarded as a great sensory centre through which
afferent impulses stream on their way to all parts of the cortex.
The fibres which connect the cerebral cortex with lower levels of
the central nervous system are sometimes grouped together as
projection fibres in contradistinction to the commissural and associa-
tion fibres. A large proportion of the fibres of the corona radiata are
projection fibres, including efferent groups (pyramidal tract, fronto-
pontine fibres, temporo-
pontine fibres) and afferent
groups (the fillet system,
thalamo-cortical fibres from
the grey matter of the
thalamus to the cortex, in-
cluding the optic radiation).
SECTION VII. — CONNECTIONS
OF BRAIN STEM WITH CORD
— CONNECTIONS OF CERE-
BELLUM.
Connections of the Vestibulo-
Spinal or Antero-Lateral De-
scending Tract. — The main
origin of these fibres is the
nucleus of Deiters, a collection
of large multipolar nerve-cells
in the floor of the fourth ven-
tricle near the inner auditory
nucleus. This nucleus consti-
tutes an important intermedi-
ate station between the cere-
bellum and the cord. Its
cells give off axons which pass
into the posterior longitudinal
bundle of the bulb and pons,
mostly to the bundle of the
same side, but partly into that
of the opposite side. Here the
fibres bifurcate into an ascend-
ing branch, which passes up to
the oculo-motor nucleus, and a
descending (vcstibulo - spinal)
branch, which passes down-
wards to the spinal cord and
enters the antero-lateral de-
Fig. 361. — Fibres connecting Frontal and
Temporo-Occipital Lobes with Cerebellum,
etc. (Diagram) (after Gowers). Fr, frontal,
Oc, occipital lobe ; interrupted lines indicate
fibres (TOC) connecting cerebellum and
temporo-occipital cortex, and fronto-cere-
bellar fibres (FC). On left side the position
of these two groups of fibres and of motor
(pyramidal) tract, PY, in the crus, is indi-
cated by letters. The pyramidal tract is
seen on the right passing down from the
Rolandic area through posterior limb of
internal capsule 1C (the genu or knee of
which is indicated by asterisk) to decussate
in the bulb. AF, ascending frontal convolu-
tion; AP, ascending parietal convolution;
FR, fissure of Rolando; IPF, intraparietal
fissure; PCF, precentral fissure; Ipt, crossed
pyramidal, apt, direct pyramidal tract.
scending tract. The fibres of
Ihis tract ultimately pass into the anterior horn, where most of them
end by arborizing amongst the cells of the horn. Higher up corre-
sponding fibres from the posterior longitudinal bundle arborize in the
cranial motor nuclei.
Connections of the Rubro-Spinal Tract. — These fibres, as the name
given to the bundle implies, originate in the red nucleus and run down
into the cord. A little distance from their cells of origin they cross the
CONNECTIONS OF CEREBELLUM
885
median line, and then pass down first in the tegmentum, and below that
in the lateral column of the bulb and cord. On their way they come
into relation with the motor nuclei of the cranial nerves, and in the
cord with the cells of the anterior horn. It is obvious that in contrast
to the projection fibres the fibres of the rubro-spinal, vestibulo-spinal,
olivo-spinal, and thalamico -spinal tracts (p. 867) and the posterior
longitudinal bundle connect the brain stem or cerebral axis with the
cord, or different levels of the brain stem with each other.
Connections of the Grey Matter of the Cerebellum with the Periphery
and other Parts of the Central Nervous System. — Numerous as are the
nervous ties of the cerebral cortex, those of the grey matter of the
cerebellum are, in proportion to its mass, still more extensive, particu-
larly as regards afferent fibres, and perhaps not less important.
Speaking broadly, we may say that the restiform body or inferior
peduncle connects chiefly the dentate nucleus and the grey matter of
the worm with the spinal cord and medulla oblongata, and through
them with the periphery. The fibres which it receives from the direct
Fig. 362. — Direct Sensory Cerebellar
Path of Edinger. D, Deiters'
nucleus; v, median nucleus of
auditory nerve; t, nucleus of the
roof; g, nucleus globosus.
. e
Fig- 363- — Diagram of Dorsal and Ventral Spino
Cerebellar Tracts entering Cerebellum (Mott).
P.C.Q., posterior corpora quadrigemina; s.v.,
superior vermis of cerebellum; d.a.c., v.a.c.,
dorsal and ventral ascending Cerebellar tracts.
cerebellar tract (dorsal spino-cerebellar tract) of its own side it carries
to the worm. These fibres occupy the outer portion of the peduncle.
The fibres which reach the restiform body from the olivary nucleus of
the opposite, and ako in smaller numbers from that of the same side,
run mainly to the hemisphere. All these fibres are afferent in relation
to the cerebellum (cerebello-petal) . An uncrossed afferent connection
also exists between the cerebellum and the vestibular branch of the
auditory nerve, through certain of its nuclei of reception, and also
between it and the nuclei of other cranial nerves, such at> the trigeminus
and the vagus. The fibres pass up in the inner portion of the inferior
peduncle (direct sensory cerebellar path of Edinger, Fig. 362) to the
nucleus of the roof (nucleus tecti) and nucleus globosus. Some efferent
fibres (cerebellofugal) also run down from the cerebellum in the inferior
peduncle, including fibres from the nucleus tecti of the opposite side
which are on their way to the medulla oblongata.
886
THE CENTRAL NERVOUS SYSTEM
The middle peduncle is in the main a link between the cerebellar
cortex and the cerebral cortex of the opposite side, through the relay
of the pontine grey matter. Most of the fibres in it are afferent in rela-
tion to the cerebellum, their cells of origin being situated in the nuclei
of the pons, and sending their axons across the middle line to end in the
cerebellar cortex.
The superior peduncle connects chiefly the dentate nucleus of one
side with the cortex of the opposite cerebral hemisphere through the
red nucleus of the tegmentum of the crus cerebri and the optic thalamus
on the opposite side. The great majority, or perhaps all, of its fibres
are efferent fibres as regards the cerebellum — i.e., their cells of origin lie
in the dentate nucleus. Running upwards and forwards in the superior
peduncle towards the mid-
brain they cross the middle
line below the corpora
quadrigemina, and then
bifurcate into ascending
and descending branches.
The ascending branches end
mainly in connection with
cells in the red nucleus, but
some of them pass on to
the optic thalamus, with
which cells of the red
nucleus are also connected.
The thalamus, as we have
seen, is in its turn exten-
sively connected with the
cerebral cortex, and the
red nucleus (by the efferent
tract of Monakow) with the
grey matter of the cord.
Fig- 364. — Paths of Middle Cerebellar Peduncle
(Mingazzini). The scheme indicates the afferent
and efferent paths which run through the middle
cerebellar peduncle, connecting cerebellum with
opposite side of cerebrum, a, fibre coming from
a cell in the nuclei pontis and going to the cere-
bellar cortex; b, fibre from a cell in cortex of
The descending branches
of the fibres of the superior
peduncle, entering the re-
tic ular formation of the
pons, pass down, it is said,
to make connection with
the motor nuclei of the
cranial and spinal nerves.
The tract of Gowers, as
previously stated, comes
into relation with the su-
opposite cerebral hemisphere making connection
in the pons with a (a and b together constitute
an afferent path to the cerebellum); c, a fibre
springing from a Purkinje's cell in the cerebellar
cortex and making connection in the pons with
a cell d, which sends its axon to the cerebral
cortex of the opposite side, c and d constitute
an efferent path from cerebellum to opposite
cerebral hemisphere; e, f, represent a path
, coming from the cerebellar cortex, which crosses
the middle line in the pons, and then ascends
till it loses itself in the formatio reticularis.
perior peduncle, passing
backwards along its mesial border to the worm. Since the cortex of the
cerebellum is linked to the dentate nucleus, the superior peduncle affords
an indirect connection between it and the cerebral cortex. Through
the restiform body afferent impulses pass up to the cerebellum. From
the cerebellum they may proceed to the cerebrum. So that the path by
the restiform body, dentate nucleus, and superior peduncle may form an
alternative route for afferent impressions ascending from the periphery to
the great brain — a path broken by at least four relays of nerve-cells.
The cerebellar hemisphere may be connected by an efferent path through
the nucleus of Deiters and the descending antero-lateral tract with the
.motor roots of the same side. Another efferent path (from the dentate
nucleus) may be constituted by the fibres of the superior peduncle and
Monakow' s bundle.
FUNCTIONS OF CENTRAL NERVOUS SYSTEiM 887
We have purposely omitted to enumerate other paths by which
the various tracts of grey matter in the brain are brought into com-
munication with each other, and our knowledge of such connections
is no doubt far from complete. When we add that not only are the
cerebral hemispheres united by many ties to the subordinate portions
of the cerebro-spinal axis and to each other, but that cortical areas
of one and the same hemisphere are in communication by short
connecting loops of ' association ' fibres (Fig. 360), it will be seen that
the linkage of the various parts of the central nervous system is
extremely complex; that an excitation, blocked out from one path,
may have the choice of many alternative routes; and that the ap-
parent simplicity and isolation of the pyramidal tracts must not be
allowed too far to govern our views of the possibilities open to a
nervous impulse once it has been set going in the labyrinth of the
nervous network. Nor is it only by the main channel of the axis-
cylinder that nervous impulses can be conducted, they can also pass
along the collaterals. And the actual route taken by a given impulse
is determined not only by anatomical relations, but also by molec-
ular conditions, particularly in the terminal fibrils of the axons,
collaterals and dendrites, and in the substance, if such a substance
there be, which intervenes between the end arborizations of a neuron
and the dendrites or cell-bodies of the neurons with which they lie in
contact. So that a road open at one moment may be closed at
another. (See p. 902.) We may suppose that the greater the number
of connections between the cells of the central nervous system, the
greater is the complexity of the processes which may be carried on
within it. And, indeed, comparison of the brains of different animals
shows that it is not so much by excess in the number of nerve-cells
as by the increased complexity of linkage, that a highly-developed
brain differs from a brain of lower type; the higher the brain, the
more richly branched are the dendrites and the terminations of the
axons and their collaterals, and, therefore, the greater is the numbei
of possible paths between one nerve-cell and another.
SECTION VIII. — FUNCTIONS OF THE CENTRAL NERVOUS SYSTEM —
(i) THE SPINAL CORD (INCLUDING THE MEDULLA OBLONGATA).
Much of our knowledge of the functions of the central nervous
system and of its divisions has been gained by the removal or
destruction of more or less extensive tracts of nervous substance, or
the cutting off of connection between one part and another. But it
is well to warn the reader at the very outset that in no other part of
physiology is such caution required in making deductions as to the
working of the intact mechanism from the phenomena which mani-
fest themselves after such lesions.
888 THE CENTRAL NERVOUS SYSTEM
In the first place, every operation of any magnitude on the brain or
cord is immediately followed by a depression of the functional power of
the nervous tissue distal to the lesion, a depression which may extend
far from the actual seat of injury and manifest itself by various phe-
nomena, which are grouped together under the name of ' shock,' better
termed spinal or cerebro-spinal shock, to distinguish it from the cardio-
vascular or surgical shock already mentioned (p. 192). Thus, when the
spinal cord of a dog is divided, e.g., in the dorsal region, all power, all
vitality, one might almost say, seems to be for ever gone from the
portion of the body below the level of the section. The legs hang limp
and useless. Pinching or tickling them calls forth no reflex movements.
The vaso-motor tone is destroyed, and the vessels gorged with blood.
The urine accumulates, overfills the paralyzed bladder, and continually
dribbles away from it. The sphincter of the anus has lost its tone, and
the faeces escape involuntarily. And if we were to continue our observa-
tions only for a short time, a few hours or days, we should be apt to
appraise at a very low value the functions of that part of the cord
which still remains in connection with the paralyzed extremities. But
these symptoms are essentially temporary. They are the immediate
results of the section; they are not permanent ' deficiency ' phenomena.
And if we wait for a time, we shall find that this torpor of the lower
dorsal and lumbar cord is far from giving a true picture of its poten-
tialities; that, cut off as it is from the influence of the brain, it is still
endowed with marvellous powers. If we wait long enough, we shall
see that, although voluntary motion never returns, reflex movements
of the hind-limbs, complex and co-ordinated to a high degree, are readily
induced. A few months after transection of the cord it is easy to show
that, although the dog cannot use the hind limbs for continuous pro-
gression, the machinery for executing the appropriate movements exists
in the cord. When, for example, the animal is held in the proper
position and given a slight push forwards, it may take two or three steps
before its legs give way. The regulation of the movements necessary
for the maintenance of equilibrium cannot be achieved when the control
of the higher centres is eliminated. In water, where the problem of
the maintenance of the normal position is solved by the mechanical
properties of the medium, the dog can use the hind-legs in swimming.
The tone of the resting muscles below the lesion is even somewhat
greater than normal. Vaso-motor tone also comes back. The
functions of defaecation and micturition are normally performed.
Erection of the penis and ejaculation of the semen take place in a dog.
A man with complete paralysis below the loins and destitute of all
sensation in the paralyzed region has been known to become a father
(Brachet). Pregnancy carried on to labour at full term has been
observed in a bitch whose cord was completely divided above the
lumbar enlargement. The severity and duration of spinal shock are
greater in the monkey than in the dog, in man than in the monkey, and
in the whole mammalian group than in the lower vertebrates. The
mechanism of its production has been much discussed, and will be
referred to on another page (p. 912).
We cannot doubt that. the spinal cord takes an important share in
the recovery of function after shock. But here again it would be
erroneous to conclude that everything is due to the cord. For Goltz
and Ewald have been able to keep dogs alive for long periods after
preliminary section of the cord in the cervical region and subsequent
removal of large portions of it. They find tha.t even after destruction
of the lumbar and sacral regions of the cord the external sphincter of
the anus, striped and even voluntary muscle though it be, regains its
FUNCTIONS OF THE SPINAL CORD 889
tone, although it is temporarily lost after the first cervical section.
The bladder ultimately recovers the power of emptying itself spon-
taneously and at regular intervals. A pregnant bitch in which the
lumbar enlargement and the whole cord below it to the cauda equina
had been removed, and therefore all the nerve-roots supplying fibres
to the uterus cut, whelped in a normal manner, and the corresponding
mammary glands behaved exactly as the rest. Digestion went on as
usual when practically nothing of the cord except its cervical portion
was left. Certain vaso-motor phenomena were also observed which
suggest that the sympathetic system, independently of the cerebro-
spinal system, is itself possessed of regulative powers (p. 183).
Secondly, we must not run into the opposite error, and assume,
without proof, that all the functions which the brain or cord is capable
of manifesting under abnormal circumstances are actually exercised by
either when, under ordinary conditions, it is working along with and
guiding, or being guided by, the other. For example, in many animals
certain of the reflex powers of the cord are, if not increased, at all events
more freely exercised when the controlling influence of the higher centres
has been cut off than when the central nervous system is intact.
Thirdly, there is another class of phenomena which we must make
allowance for, and perhaps more frequently in the case of pathological
lesions in man than in experimental lesions in the lower animals. This
is the class of ' irritative ' phenomena. The irritation set up by a blood-
clot or a collection of pus, or in any other way, in a wound of the grey
or white matter, may cause a stimulation of nervous tracts by which,
for a time, the ' deficiency ' effects of the lesion may be masked.
In the fourth place, we must not hastily conclude that, when no
obvious deficiency seems to follow the removal of a portion of the central
nervous system, the function of that portion must necessarily be of
such a nature as to give rise to no objective signs. For there is reason
to believe that, to a certain extent, the function of one part may, in its
absence, be vicariously performed by another.
Bearing in mind the cautions we have just been emphasizing, we
may broadly distinguish between the functions of the cord (including
the bulb) and those of the brain proper by saying that the cord is
essentially the seat of reflex actions, the brain the seat of automatic
actions and conscious processes. But neither of these conceptions
is entirely correct. Both err by defect and by excess. The brain,
it is true, is pre-eminently automatic. The movements which are
started in the grey matter of the cerebral cortex are pre-eminently
voluntary (p. 946), but we cannot deny to the brain the possession of
reflex powers as well. The movements in which the only nerve
centres concerned are those of the spinal cord are above all reflex
(p. 897)- But some of its centres, and especially those lying in the
medulla oblongata — e.g., the respiratory centre — are, much as they
are influenced by afferent impulses, capable of discharging auto-
matic impulses too. And while consciousness is certainly bound up
with integrity of the brain, and in all the higher mammals is asso-
ciated with cerebral activity alone, it has been plausibly maintained
that the spinal cord, even of such an animal as the frog, may also be
endowed with something which might be called a kind of hushed
consciousness. Whether this be so or not for the frog, with its
THE CENTRAL NERVOUS SYSTEM
distinct though relatively ill-developed cerebral hemispheres, it
would seem by no means unlikely in the case of fishes and animals
below them, which are practically devoid of a cerebral cortex
altogether.
The functions of the spinal cord may be classified thus:
1. The conduction of impulses set up elsewhere — either in the
brain or at the periphery.
2. The modification of impulses set up elsewhere (reflex action).
3. The origination of impulses (?).
Cerebral
Fi.bre.for
Jfead J
fiecussation
cf Pyramids
ofDi.rect.
Pyramidal tract
cfAnt%m !5T
-TniTxjl Arborisation
of a Pyramids I Fibre,
around, cell of
' ' ffow
Anterior
Root
Fibres
Fig- 365. — Some Possible Paths of Efferent Impulses in the Central Nervous System
(Schematic). Details are omitted from the scheme. For instance, each pyra-
midal fibre is represented as arborizing around one anterior cornual cell only,
and no collaterals are shown. The hypothetical intercalated neurons between
the pyramidal fibres and the anterior horn cells (p. 876) are not shown.
I. Conduction of Nervous Impulses by the Cord. — The old con-
troversy as to whether the white fibres of the spinal cord are directly
excitable has long been settled in the affirmative.
The inquiry was complicated by the presence of the spinal roots,
which, since the experiments of Charles Bell, have been known to be
capable of excitation by artificial stimuli. But at length the difficulty
was overcome in this way: The posterior (dorsal) portion of several
FUNCTIONS OF THE SPINAL CORD 891
segments of the cord with the attached posterior roots and the grey
matter was excised. Long strands of the white matter of the anterior
(ventral) portion of the cord were isolated, and laid on electrodes, and
contractions of muscles were seen to follow stimulation, even when the
anterior roots nearest the stimulating electrodes had been cut, and every
precaution taken to avoid escape of current on to the distant anterior
roots of the nerves supplying the muscles. Indeed, apart from direct
experimental evidence, the fact that the white fibres of the brain are
universally admitted to be excitable by artificial means would be of
itself almost sufficient to decide the question, for we know of no essential
difference between the cerebral and the spinal fibres. But the con-
ditions must rarely occur under which direct stimulation of white fibres
in their course is possible in the intact body ; and the only impulses with
which we need concern ourselves here are those that reach the con-
ducting paths from grey matter in the cord itself or in the brain, or from
the peripheral organs.
What sort of impulses do the various tracts of the spinal cord
conduct ? For the dorsal or posterior roots this question was first
fully answered by Magendie; for the venlial or anterior roots,
although with a certain degree of ambiguity, by Sir Charles Bell.
Bell observed that when, in an animal just killed, he mechanically
stimulated the anterior roots, muscular contractions were obtained
at each touch of the forceps. He concluded that the anterior roots
are motor^and sensory, while the posterior roots are ' vegetative ' —
i.e., connected ^wrfh" the functions of the viscera, the so-called
' vegetative ' organs. But although he is often credited with the
discovery of the functions of the posterior roots as well, he was not
the first to make the decisive experiment necessary to show that they
are the conductors of sensory impulses. It was after Magendie's
discovery that only a portion of the nerves are sensitive, and that
there are nerves ' which are like tendons, aponeuroses, or cartilages
in insensibility/ that Bell formulated the law that the anterior roots
are purely motor, the posj£»or purely sensory. This law, often
termed Bell's Law, is more correctly denominated the Magendie-
Bell Law.
When the posterior roots are divided, loss of sensation occurs in
the region to .which they are distributed. If only one root is cut,
the loss of sensation is never complete in any part of the skin ; and
Sherrington has found that the cutaneous areas of distribution of
consecutive nerve-roots are not perfectly independent, but to some
extent overlap. Stimulation of the peripheral end of the divided
posterior root has no effect. Stimulation of the central end gives
rise, if the animal be conscious, to evidences of pain, and other signs
of the passage of afferent impulses — e.g., a rise in blood-pressure.
The latter may also be observed when the animal is anaesthetized.
Referred Pain. — The posterior roots contain sensory fibres not only
for the skin, but also for the deeper structures and the viscera. The
afferent fibres reach the viscera by the sympathetic, the vagus, and the
pelvic nerves or nervi erigentes. Clinical observations have thrown
892 THE CENTRAL NERVOUS SYSTEM
much light upon the distribution of the visceral fibres and their rela-
tion to the cutaneous sensory nerves. It has long been known that
in disease of an internal organ the pain is often referred to some super-
ficial part. It has now been demonstrated that each organ is related
to a more or lees definite region, or more than one region, of the skin.
In disease of the organ there is in this area increased excitability
(hyperalgesia) or tenderness to slight mechanical stimuli, and often
also increased excitability for heat or cold, and the reflexes elicited by
stimulation are exaggerated (Head, Dana).
The bond of connection appears to be the origin from the same spinal
segments of the autonomic* sensory fibres of. any viscus and the sensory
supply of the corresponding cutaneous area. The common anatomical
origin seems to carry with it a physiological correlation, either because
the irritation of the visceral fibres spreads in the cord to the somatic
afferent fibres which enter the corresponding segments, or because of
some action higher up in the cerebral centres, the nature of which will
be best considered along with the general topic of the localization of
sensory impressions (Chapter XVIII.) .
Recurrent Sensibility. — Although muscular contraction is the
most conspicuous event that follows stimulation of the peripheral end
of an anterior nerve-root, it is by no means the only one. It is
frequently observed, though not' in all kinds of animals, that here,
too, pain is caused. That this pain is not due to the muscular con-
traction is proved by the fact that it can still be elicited when the
nerve-trunk is divided between the junction of the roofs and the
periphery. The real explanation of the phenomenon is that certain
fibres from the posterior roots (' recurrent fibres/ see footnote on
p. 797) bend up for some distance into the anterior roots, and then
turn round again and pursue their course to their peripheral dis-
tribution in the mixed nerve, or run on in the motor roots to supply
the sheath surrounding them (nervi nervorum), and even the mem-
branes of the spinal cord.
The afferent impulses that enter the cord along the posterior roots
have the choice of many paths by which they may reach the brain.
The following are a few of the routes which they may follow :
(1) They may pass directly up through the postero-median column.
If they take this route, their course will be first interrupted by nerve-
cells in the gracile or cuneate nuclei in the medulla oblongata. Thence
they may find their way across the middle line by the arcuate fibres of
the upper or sensory decussation, and, sweeping along the fillet and the
sensory path in the hinder part of the posterior limb of the internal
capsule, finally arrive at the cerebral cortex. Between the gracile and
cuneate nuclei and the cortex they pass through nerve-cells in the optic
thalamus.
(2) They may pass up by the direct cerebellar tract and restiform
body to the grey matter of the cerebellar worm. If they take this
route their course will be interrupted very soon after their entrance into
* Langley uses the term autonomic nervous system to include the nerve
supply of heart muscle, all unstriated muscle, and all gland cells in, the body.
It embraces, in addition to the sympathetic, cranial autonomic fibres in
several of the cranial nerves and sacral autonomic fibres in the nervi erigentes
(see Chapter XVII.).
FUNCTIONS OF THE SPINAL CORD 893
the cord in the cells of Clarke's column. Since the superficial grey
matter of the vermis is connected by association fibres with the dentate
nucleus, and the dentate nucleus by the superior peduncle with the oppo-
site cerebral hemisphere, this is also a possible path to the great brain.
(3) They may reach the antero-lateral ascending tract of the same
side through its cells of origin in the spinal grey matter, and, passing
through the medulla and pons to the superior peduncle of the cere-
bellum, enter the grey matter of the superior worm.
(4) They may cross the middle line, after entering the cord, through
axons or collaterals (p. 872) which run in the anterior and also in the
posterior commissure, enter one of the ascending tracts on the other
side — e.g., the tract of Gowers — and continue without further decus-
sation up to their central destination.
(5) They may spread from neuron to neuron in the tangle of the grey
matter itself, and pass out again at a different level into one of the
white tracts on the same or on the opposite side of the cord.
Efferent impulses from the brain may travel —
(1) Through the direct or crossed pyramidal tract.
(2) From one side of the cerebral cortex to the other, and then down
the pyramidal tracts corresponding to that side (?).
(3) From the frontal part of the cerebral cortex, through the anterior
limb of the internal capsule to the grey matter in the pons, and thence
to the cerebellum by its middle peduncle.
(4) From the occipital or temporal cortex, in the hinder rim of the
internal capsule, to the pontine grey matter, and through the middle
peduncle to the cerebellum. From the cerebellum they may possibly
pass down to the nucleus of Deiters and thence along the antero-lateral
descending tract to the anterior horn of the cord, and indirectly to the
periphery.
All the paths enumerated, as well as others to which it would be
tedious to formally refer, and which the ingenuity of the reader may
profitably be employed in constructing for himself, from the data
already given, are to be looked upon as possible channels for the
passage of impulses between the brain and the periphery. But it
must be distinctly pointed out that what is certain is in this case
much more limited than what is possible. Among the efferent paths
it is certain that the pyramidal tracts are conductors of voluntary
motor impulses, and that in most individuals the great majority of
such impulses decussate in the medulla oblongata, only a small
minority in the cord. For a lesion involving the pyramidal tract
above the decussation of the pyramids causes paralysis of the oppo-
site side of the body, a lesion below the decussation paralysis of the
same side. It is certain that when one pyramidal tract has been
destroyed, in many animals at least, the resulting paralysis is soon
recovered from, at any rate to a great extent, and it is possible that
in this case the motor cortex on the side of the lesion has placed itself
again in communication with the paralyzed muscles through its
commissural connections with the opposite hemisphere. This,
however, is not the only alternative, for, as already pointed out, the
pyramidal tracts are not the only cortico-spinal paths which can
894 THE CENTRAL NERVOUS SYSTEM
subserve volitional movements, and division of the anterior portion
of the antero-lateral column may cause deeper and more permanent
paralysis than division of the pyramidal tract.
In the dog total section of the pyramids is not followed by com-
plete paralysis of voluntary movements, and stimulation of the
cortical motor areas can still elicit characteristic movements. It is
obvious that impulses emanating from the cortex can reach the
motor nuclei of the cord by other routes than the long pyramidal
fibres, possibly by paths with several segments, of which, for
example, the rubro-spinal tract (p. 867) may be one. Just as an
important business house may find it useful or indispensable to
supplement or replace the common telegraph service by private wires
in the interest of more prompt and satisfactory communication with
its principal correspondents, while still utilizing the ordinary channels
to some extent, so the higher brains may be supposed to have
developed more and more the direct service of the pyramidal tract
to tighten the grip of the cortex upon the motor nuclei of the cerebro-
spinal axis, while still availing themselves, although in diminishing
degree as their evolution proceeds, of the more primitive indirect
paths.
Decussation of the Sensory Paths. — On the other hand, it is certain
that pathological or traumatic lesions, apparently involving the
destruction of one lateral half of the cord in man and experimental
jemisections in some mammals, are followed by symptoms which
suggest that some kinds of sensory impulses decussate chiefly in the
spinal cord — viz., diminution or loss of sensibility to pain and to
changes of temperature on the opposite side below the level of the
lesion, with little or no impairment, and often increase of sensibility
(hypersesthesia) on the same side. Tactile sensibility is lost on the
side of the lesion, and likewise the muscular sense.
The first general description of this symptom-complex was given by
Brown-Sequard. On the basis of clinical observations in man, he
came to the conclusion that unilateral lesions of the cord, equivalent
approximately to a semisection, are associated with muscular paralysis
below the level of the lesion on the same side, and loss of cutaneous
sensibility on the opposite side, while on the side of the lesions there
may be an augmentation of sensibility. He interpreted these facts as
meaning that the sensory path decussates soon after its entrance into
the cord. The sensory path from the left side is therefore spared by a
lesion of the left side of the cord, but interrupted by a lesion of the
right side of the cord. The left and right motor paths, having already
decussated in the bulb, are cut by lesions in the left and right halves of
the cord respectively. Long afterwards Brown-Sequard saw cause to
retract this interpretation of the facts observed by him, but the majority
of subsequent observers have considered his original hypothesis more
satisfactory than his later ones. While it may be true that in man it has
not been rigidly demonstrated that the symptoms are associated with
a clean-out lesion precisely limited to one-half of the cord, clinical
observation lias on the whole tended to confirm the view that an
FUNCTIONS OF THE SPINAL CORD 895
important portion of the sensory path decussates in the cord. But it
is a curious circumstance that experimental physiologists have for the
most part obtained contradictory results. Thus Mott, working with
monkeys, found that the different kinds of sensation, far from being
abolished, are as a rule impaired in a smaller degree on the side opposite
to the semisection than on the same side, while Ferrier and Turner
obtained on the whole a contrary result, and one that corresponded
closely with Brown-Sequard's original description. The discovery that
no ascending degeneration, or only a trifling amount, is to be found on
the opposite side of the cord, either after semisection or after division
of posterior roots, does not of itself enable us to decide the question.
For while this latter fact shows that few or none of the afferent fibres
cross the middle line to enter the long conducting paths before being
interrupted by nerve-cells, it by no means proves that afferent impulses
do not decussate in the cord. The long paths of the posterior column,
indeed, do not decussate below the level of the bulb. The dorsal and
ventral spino-cerebellar tracts are also, in the main at least, uncrossed
spinal paths. A portion of the afferent impulses must therefore be
carried up to the cerebrum and the cerebellum without decussating in
the cord. But nobody can tell how massive a link between the two
halves of the cord may be formed by the grey matter and the endogenous
fibres of the white columns and their collaterals. We know that some
afferent impulses do decussate far below the level of the medulla. For,
(i) A part of the action current (p. 838) crosses the middle line and
ascends in the opposite half of the cord when the central end of one
sciatic is stimulated (Gotch and Horsley). (2) Crossed reflex move-
ments are possible ; and when excitation of the central end of the sciatic
is followed by contraction of the muscles of the opposite fore-limb, the
afferent impulses must either decussate in the lumbar cord, and then
run up on the opposite side to the level of the brachial plexus, or must
ascend on the same side and cross over somewhere between the plane
of the sciatic and the brachial nerve-roots. The only other hypothesis
on which crossed reflex action can be explained — but a hypothesis for
which there is not a tittle of evidence — is that the afferent impulse
always acts on the few motor cells whose axis-cylinder processes pass
over to the opposite side, and there enter anterior nerve-roots. But
while, for these reasons, it cannot be denied that some afferent impulses
decussate in the cord, it would be an error to conclude that all do so in
any animal, or that all animals are in this respect alike. It is indeed
extremely probable that in different species of animals, and even in
individuals of the same species, there are considerable differences in
the extent of the sensory decussation in the cord, just as there are in the
extent of the motor decussation in the bulb. In some animals the
greater part of the sensory path may decussate in the cord ; in others the
greater part may decussate in the bulb, or higher up. The lack of
agreement in the experimental results may be due partly to this cause.
When it is further remembered how difficult it sometimes is to interpret
the account which a man gives of his sensations, and to recognize
precisely the degree and nature of sensory defects produced by disease
in the human subject, it will not be thought surprising that experi-
ments on animals, from the time of Galen onwards, should have yielded
evidence which, although perhaps now at length tending to a definite
result, is still unfinished and in part conflicting.
If, leaving them out of account, not as valueless but as still
difficult of interpretation, we attempt to draw any general conclusion
896 THE CENTRAL NERVOUS SYSTEM
from the clinical observations which, however imperfect, are in such
questions our surest guide, it can only be this, that in man some
of the sensory impulses, and particularly those connected with the
cutaneous sensations of pain and temperature, decussate, in part at
least, in the cord. But there is also evidence that tactile afferent im-
pulses, including those coming from the muscles and related to the
muscular sense, and, it may be, some of the impulses associated with
pain, decussate, not in the cord, but in the bulb.
The Paths for Different Kinds of Sensory Impressions. — If this is the
state of our knowledge where the problem is merely to determine the
crossing-place of afferent impulses which are certainly known to cross,
it is only to be expected that we should be still more in the dark as
regards the routes by which different kinds of afferent impulses thread
their way through the maze of conducting paths in the neural axis to
reach their planes of decussation and gain the ' sensory crossway ' in
the internal capsule. Some authors have indeed cut the Gordian knot
by assuming that any kind of sensory impression may travel up any
afferent path. Direct stimulation of a naked nerve-trunk, it has been
argued in favour of this view, gives rise to a sensation of pain; stimula-
tion of the skin in which the end-organs of the nerve lie gives rise to a
sensation of touch or a sensation of temperature, according as the
stimulus is a mild mechanical or a thermal one, the contact of a feather
or of a hot test-tube. Why, it has been asked, should we imagine that
the difference in the result of stimulation depends on a difference in the
nerve-fibres excited, and not on a difference in the kind of impulses set
up in the same nerve-fibres ? This is a question which we shall have
again to discuss. But apropos of our present problem, we may
say that there is very clear proof from the pathological side that a
limited lesion in the conducting paths of the central nervous system
may be associated with defect or total loss of one kind of sensation, while
all the other kinds remain intact. And there seems no other tenable
hypothesis than that in such cases the pathological change has picked
out a particular group of fibres, either collected into a single strand or
scattered among unaltered fibres of different function. For example,
in syringo-myelia, a condition in which cavities are formed in the grey
matter of the cord secondary to a new growth of the neuroglia surround-
ing the central canal, a frequent symptom is the loss in a certain region
of sensibility to pain and to changes of temperature, while tactile
sensibility is unaffected (dissociation of sensations). Again, in loco-
motor ataxia, a disease in which inco-ordination of movement and
derangement of the mechanism of equilibration are prominent symptoms,
degeneration in the posterior column of the cord is a most constant
lesion. And there is strong evidence that afferent impulses from
muscles and tendons, which either give rise to impressions belonging to
the group of tactile sensations, or produce no effect in consciousness, and
which, according to the most widely accepted doctrine, serve as the
basis of the muscular sense, and play an important part in the main-
tenance of equilibrium (p. 941), pass up in the posterior column. It
may also conduct tactile impressions from the skin. A case has been
observed where a man received a stab which divided the whole of one
side of the cord and the posterior column of the other side. Sensibility
to touch was lost on both sides of the body below the level of the injury,
sensibility to pain only on the side opposite to the main lesion. In
another case, in which some small syphilitic tumours (gummata) in
FUNCTIONS OF THE SPINAL CORb $97
the lateral column on the left side caused marked degeneration in the
left direct cerebellar tract, the tract of Cowers, and the crossed pyram-
idal tract, without affecting the posterior columns, tactile sensibility
was only slightly impaired in the opposite leg, while the sensibility for
pain and temperature was much enfeebled. In the left leg, which was
paralyzed, there was slight hyperaesthesia. These observations indicate
that impressions of pain and temperature pass up in the antero-lateral
column, either in the tract of Cowers, or in the direct cerebellar tract, or
in both (Dejerine and Thomas).
But it does not follow that they cannot ascend by other paths as
well. It appears, indeed, that the grey matter of the cord, or, rather,
short endogenous fibres arranged in series in the antero-lateral column
so as to connect the grey matter at different levels, constitute such a
path, and that impulses which give rise to pain can be propagated along
a cord in which hardly a vestige of white substance remains uncut. In
man the path for pain and temperature impressions along these short
endogenous fibres seems to be mainly or entirely a crossed path. The
afferent paths for such vaso-motor reflexes as are elicited by stimulation
of the central end of the sciatic ascend in the lateral column, and the
impulses largely cross the middle line in the cord. The posterior
columns have nothing to do with the conduction of painful impressions,
for division of them causes not anaesthesia, but rather hyperaesthesia,
while if they are left intact, and the rest of the cord, including the grey
matter, divided, the animal is insensitive to pain below the level of the
lesion. Just as man differs from lower animals in the completeness
with which certain of the sensory impressions decussate in the cord, so
differences exist in the degree of localization of the different kinds of
impressions in particular tracts. One of the outstanding differences is
that in animals it seems to be easier for a still intact path to be substi-
tuted for a severed path as a conductor of impulses which normally
traverse the latter. The rapidity with which sensation is restored
below the lesion after semisection of the cord in animals is an illustration
of this. Another difference, which can be explained in the same way, is
that a sharply-marked dissociation of sensations — retention of tactile
sensibility, for example, with loss of sensibility to pain or to pain and
temperature changes — either cannot be produced experimentally in
animals, or is very difficult to realize.
The impulses which descend the cord give token of their arrival at the
periphery by causing either contraction of voluntary muscles, or con-
traction of the smooth muscular fibres of arteries, or secretion in glands.
They all pass down in the antero-lateral column, but the path of the
voluntary impulses in the pyramidal tracts is the best known and most
sharply defined.
2. Modification of Impulses set up elsewhere (Reflex Action). —
The spinal cord, although it is a conductor of nervous impulses
originating elsewhere, is by no means a mere conductor. Many of
the impulses which fall into the cord are interrupted in its grey
matter. Some of the efferent impulses proceeding from the brain
are perhaps modified in the cord, and then transmit ted to the muscles.
Some of the afferent impulses are modified, and then transmitted to
the brain ; some are modified, and deflected altogether into an efferent
path. These last are the impulses which give rise to reflex effects.
A reflex action has sometimes been defined as an action carried out
in the absence of consciousness: not necessarily, however, in the
57
898 THE CENTRAL NERVOUS SYSTEM
absence of general consciousness, but in the absence of consciousness
of the particular act itself. But the term is now more correctly
used so as to embrace all kinds of actions which are not directly
voluntary, whether the individual is conscious of them or not. For
example, when the sole of rhe foot is tickled, the leg is irresistibly
and involuntarily drawn up by reflex contraction of its muscles; yet
the person is perfectly cognizant both of the movement and of the
sensation which accompanies the afferent impulse. Many reflex
actions usually associated with sensations proceed normally when
consciousness is entirely in abeyance; during sleep most of the
ordinary reflexes can be elicited.
Anatomical Basis of Reflex Action. — Since the essence of reflex action
is that the arrival of afferent impulses in the spinal cord or brain causes
the discharge of efferent impulses, there must be some connection
between the incoming and the outgoing nerve-fibres. In unicellular
animals, such as amoeba, there is no differentiation of any special
nervous or conducting path. A stimulus applied at one point may
cause contraction anywhere. Even in the lowest multicellular animals
or metazoa — e.g., in the sponges — there is no special nervous tissue.
In some species of hydra, however, many of the surface or ectodermic
cells (p. 6) possess deeply-placed contractile or muscular processes,
and stimulation of the surface cells is followed by contraction of these
processes. We may imagine that the first beginnings of an actual
nervous system may have arisen by a further differentiation of such
an ectodermic cell into a receptive portion at the surface, a deeper con-
tractile portion, and an intermediate strand of protoplasm connecting
the two, and capable of conducting the excitation from surface to
muscular process. In such a reflex arc the nervous link would consist
only of the conducting strand analogous to the nerve fibre joining the
receptive or sensory element to the contractile element, and the dis-
tinction between afferent and efferent fibre would not exist. When
development has gone a step further, and the neuro-muscular process
is interrupted by a second epithelial cell transformed into a nerve-cell,
the afferent fibre enters one pole and the efferent fibre leaves the other
pole of the same cell. It is this condition which we actually find when
the nervous system first emerges in the animal scale as an unmistakably
differentiated structure — namely, in the Ccelenterates in such forms as
the jellyfishes. Here the three types of cell, receptive or sensory cell,
reactive or central cell, and motor or contractile cell, are connected
together by conducting paths or nerve-fibres. In a simple reflex action
three events can be distinguished : stimulation of a receiving mechanism,
conduction of the excitation, and the consequent reaction or end-effect.
The receiving mechanism or receptor may consist of ordinary sensory
nerve-endings in the skin, or of special sense-endings, as in the retina
or internal ear. The conducting mechanism or conductor in all except
the very simplest nervous systems is made up of at least two neurons,
one the afferent portion of the reflex arc connected with the receptor,
the other the efferent portion of the arc, connected with the organ,
sometimes termed the effector organ — a muscle, e.g., or a gland — which
accomplishes the end-effect. The transference of the excitation from
the afferent to the efferent neuron takes place across the intervening
synapce. The simple isolated reflex arc, as thus described, although
a convenient abstraction, corresponds but little to anything which
actually exists in one of the higher animals. With increasing com-
FUNCTIONS OF THE SPINAL CORD 899
plexity of organization the nervous impulse passing up an afferent
fibre is in general offered, instead of a single efferent path, a choice of
many potential routes when it reaches the spinal cord. We have
previously (p. 872) described the course taken by the fibres of the
posterior roots on entering the cord. It is obvious that through the
main fibres and their collaterals an extensive connection — partly direct,
partly by the link of intermediate neurons — is established with the
motor cells on both sides of the cord. But the facts of physiology
demonstrate an even ampler connection than the mere anatomical
study of the distribution of the root-fibres would suggest. Indeed, the
phenomena of strychnine-poisoning seem to show that every afferent
fibre is potentially connected with the motor mechanisms of the whole
cord, or at least with a very large proportion of them. For in a frog under
the influence of this drug, stimulation of the smallest portion of the skin
will cause violent and general convulsions, which are unaffected by de-
struction of the brain, but cease at once on destruction of the cord (p. 904) .
In an unpoisoned reflex frog — that is, a frog in which interference
with the single spinal reflexes has been prevented by section of the bulb
or destruction of the brain — the movements resulting from stimulation
of a given receptive area are by contrast surprisingly limited, localized,
and constant. Thus, a harmful stimulus of a certain intensity applied
to a toe will elicit time after time a raising of the leg — in other words,
an excitation of muscles whose motor nerves arise from cells in the same
region of the cord into which the afferent fibres from the receptive skin
area enter. The localization of the reflex is in this case without, doubt
dependent upon the fact that the connections of the afferent fibres with
the group of efferent neurons in question are more direct and more
intimate than with any other group. This anatomical isolation of a
given reflex arc is never complete, but so far as it goes it may be
assumed to be constant and incapable of variation. Under normal
conditions the anatomical isolation is always supplemented by a
physiological isolation, which is susceptible of variation in the direction
either of increase or of diminution.
It is therefore a question of great interest how the isolated con-
duction of the impulses in a given reflex arc, in so far as it depends upon
the physiological condition of the arc and of its connections, is normally
achieved. The best answer which can at present be given is that it is
not equally easy for a reflex excitation to pass across all the synapses
which, are potentially open to it, and that a lowering of the resistance
of the synapses in the favoured path is probably quite as important a
factor in the isolation as an increase of the resistance in those which
are to be barred. Following the path of least resistance, the excitation
traverses the synapse or synapses which it is easiest for it to break
through. What property of the synapse is associated with resistance
to the passage of the impulse is unknown. But it is a variable property,
and when a general reduction in the resistance is produced, as by strych-
nine or tetanus toxin, an excitation impressed upon a single afferent
path may force a great many synapses normally impervious to it.
While it is convenient in a preliminary survey to speak of the resist-
ance to spreading of the excitation in the cord being diminished by
strychnine or by tetanus toxin, we shall see presently that more than
this is involved (p. 903).
Principle of the Common Path. — In considering the architecture
of the cerebro-spinal nervous system as a basis of reflex action, one
feature is of such importance as to deserve special mention. The
QOO THE CENTRAL NERVOUS SYSTEM
afferent neurons, running from the receptive surfaces to the centres,
constitute each for its own receptive point a ' private ' path which
can only be used by impulses arising at that point, and not by
impulses arising at any other point. Through its central connec-
tions an afferent neuron from a single point may be put into com-
munication with numerous efferent neurons, and thus with numerous
and distant effector organs (muscles or glands). Conversely, the
efferent portion of a single reflex arc can convey reflex excitations
originating in numerous and distant receptive fields. It is the sole
path which all efferent impulses — let them originate where they may
— must use to reach the end-organ in question. It is therefore not a
private but a public path, and may be termed in this relation the
final common path (Sherrington).
The existence of the common path is of great importance in under-
standing the manner in which reflexes are compounded together, a
problem absolutely fundamental in nervous co-ordination. One
consequence of the existence of a common path is that when, among
the receptors which may use it, two are simultaneously stimulated
which, when separately excited, produce opposite effects upon the
sffector organ, only one of the effects is produced. In other words,
impulses which produce the two opposed effects can be successively,
but cannot be simultaneously, sent along the common path. Thus,
' excitation of the central end of the afferent root of the eighth or
seventh cervical nerve of the monkey evokes reflexly in the same
individual animal sometimes flexion at the elbow, sometimes ex-
tension. If the excitation be preceded by excitation of the first
thoracic root, the result is usually extension; if by excitation of the
sixth cervical root, it is usually flexion. Yet though the same root
may thus be made to evoke reflex contraction of the flexors or of the
extensors, it does not evoke contraction in both flexors and extensors
in the same reflex response. . . . The flexor-reflex, when it occurs,
seems, therefore, to exclude the extensor- re flex, and vice versa.
Either the one or the other results, but not the two together '
(Sherrington). It is obvious that this is an advantageous arrange-
ment. An algebraical summation of the opposed effects by the
common path would result in a useless action which was neither
effective flexion nor effective extension, a compromise and not a
co-ordination. The conditions which determine which of two or
more competing reflexes shall obtain possession of the final comi
path are considered on p. 902.
Role of the Receptor in Reflex Action. — The role of the
the reflex arc is above all to sift out from the various kinds of im-
pressions impinging upon the receiving surface the particular kind
to which the appropriate response is the reflex action in question.
As will be pointed out in greater detail in the study of the special
senses, each kind of afferent end-organ has become adapted to a
FUNCTIONS OF THE SPINAL CORD 90!
special, or, as it is termed, an ' adequate ' stimulus, so that it is
easily affected by this, and with difficulty or not at all by other
modes of stimulation. Thus, light is the adequate stimulus of the
end-organ of the optic nerve, heat that of the end-organs of the
nerves by which we perceive the sensation of warmth, mechanical
pressure that of the nerves by which we perceive the sensation of
pressure. Other kinds of stimuli are either entirely inactive or much
less effective in evoking the particular sensory response. There is
every reason to believe that the receptor in the reflex arc occupies -the
same position in regard to adequate stimuli as it does when it func-
tions as a sense-organ.
$herrington has shown that the different kinds of nerve-endings
in one and the same area of the skin (in the dog) must be assumed to
possess totally different spinal connections, since the movements
elicited by stimuli suitable for one form of nerve-ending are quite
different from those elicited by stimuli suitable for another.
The ' extensor-thrust ' is a reflex obtained in the hind-leg of the
dog, and characterized by a brief, strong extension at the hip, knee,
and ankle. . It is only elicited by a certain kind of mechanical stimu-
lation, best in the spinal dog — i.e., in a dog whose brain has been
destroyed or severed from the cord some time before — by pushing the
tip of the finger between the plantar cushion and the pads of the toes.
The stimulus is similar to that which normally liberates the reaction
— namely, the pressure of the ground on the sole of the foot during
locomotion. The reflex cannot be obtained by electrical stimula-
tion or by any kind of direct stimulation of afferent nerve-trunks.
The same is true of the pinna-reflex in the cat — i.e., the backward
crumpling of the ear elicited by squeezing or tickling its tip. The
scratch-reflex,* a scratching movement of the hind-foot, is much
more easily elicited in the spinal dog by mechanical stimulation
(rubbing, tickling, or tapping) applied to the skin of the back behind
the shoulder than by electrical stimulation, which often fails to
evoke it at all. The puzzling fact that, according to surgical ex-
perience, many of the internal organs — e.g., the ureters and bile-
ducts — can be handled, cut, and sutured without pain, while the
passage of a renal calculus or a gall-stone may cause excruciating
agony, becomes explicable in view of the apparently slight difference
which sometimes distinguishes an adequate from an inadequate
stimulus. Thus Sherrington has shown that very distinct reflex
effects — e.g., a rise of blood-pressure — can be obtained by sudden
distension of the bile-duct by the injection of salt solution into its
lumen. Distension is here the adequate form of mechanical stimu-
lation, and it is the form induced by the passage of a calculus, while
nerve-cutting, although a mechanical stimulus, is not an adequate one.
* The scratch-reflex is very easily obtained in. cats during resuscitation
after a period of cerebral anaemia.
902 THE CENTRAL NERVOUS SYSTEM
Characteristic Properties of the Reflex Arc. — Conduction in reflex
arcs shows certain peculiarities when compared with the conduction
in nerve-trunks already studied (p. 781) : (i) The direction of the
reflex conduction cannot be reversed. There is an absolute block
on the passage of impulses backwards through a synapse. (2) The
velocity of conduction over the whole reflex arc is much smaller
than over a nerve-trunk of equal length. Both of these differences
depend mainly on the fact that the impulses must be transmitted
from one neuron to another, and very likely on a fundamental
property of the synapse. The delay or ' lost time ' in the discharge
of the efferent impulses which constitute the reflex response to the
excitation of an afferent path increases with the complexity of the
response — that is, with the number of neurons and therefore of
synapses involved in it. (3) The reflex arc is easily fatigued, easily
affected by deprivation of oxygen and by drugs, in comparison with
the nerve-trunk. This difference is due to the portion of the arc
in the grey matter, including the synapse or synapses. Fatigue
expresses itself by an increase in the degree of block or resistance to
the passage of impulses along the arc. (4) The reflex end-effect may
much outlast the stimulus — in other words, "a marked ' after-dis-
charge ' is characteristic of reflexes. The more intense the stimulus
which liberates the end-effect, the greater is the duration of the after-
discharge. For example, the ' crossed extension reflex ' (extension
at the knee, ankle, and hip, produced in the spinal dog by stimula-
tion of the skin of the opposite or contralateral hind-limb), when
provoked by a stimulus of more than a certain intensity, may outlast
the stimulation by ten or fifteen seconds, and the after-discharge
may be stronger than any other part of the reflex (Sherrington).
(5) A succession of impulses may easily passj.lojjg a reflex arc when
one of the series would fail to pass (temporal summation). This
does not occur in a nerve-trunk. The first stimulus, though itself
unable to produce the reflex effect, facilitates the action of succeeding
stimuli, so that summation of the impulses occurs in the cord
(Stirling). A stimulus — e.g., a make-induction shock, far too weak
to produce the scratch-reflex when applied once only to a point of
that area of skin from which the reflex is normally elicited — has been
seen to cause the reflex after more than forty shocks had been
delivered at the rate of eighteen per second. The facilitation of the
passage of an impulse by the previous passage of impulses along the
same reflex path recalls a somewhat similar phenomenon already
alluded to in connection with the conduction of the propagated
disturbance in nerve- fibres (p. 791), although in the case of the reflex
arc the effect, it may be supposed, is exerted upon the fields of
conjunction, including the synapses, between the different neurons.
There is reason to believe that summation in the reflex arc is mainly
achieved by the removal of block or resistance. The phenomenon of
FUNCTIONS OF THE SPINAL CORD 903
facilitation is probably of great importance in the acquirement of
new reactions and in rendering these acquisitions stable. It is prob-
ably one of the main physiological foundations of habit, and there-
fore of education. In this connection it is important to note that
the very same repetition of stimuli which leads to facilitation leads
to fatigue when the stimuli are applied in too rapid succession.
(6) The rhythm and intensity of the reflex end-effect correspond
much less closely with the rhythm and intensity of the stimulus than
in nerve-trunks. (7) The phenomena of refractory period (p. 155),
inhibition and ' shock,' are much more conspicuous in the reflex arc
than in nerve-trunks.
Inhibition in Reflex Action. — Special emphasis must be laid upon
the part played by inhibition in reflex actions. For the proper
carrying out of many reflex movements it is necessary not only that
the appropriate effector organ, the appropriate muscle, or group of
muscles, should be caused to contract at the proper time, but that
their contraction, or that of other muscles, should be diminished or
abolished by inhibition, or even rendered for a certain period im-
practicable by the establishment somewhere in the reflex arc of a
refractory state, which is itself a phenomenon of inhibition. There is
good evidence that this is a central inhibition — i.e., it depends on
some process occurring in the spinal portion of the reflex arc.
As an example of the numerous class of reflexes in which the
excitation of certain muscles is accompanied by the inhibition of
their antagonists (reciprocal inhibition), we may take the ' flexion
reflex,' the flexion at the knee, hip, and ankle of the hind-limb
readily elicited in the spinal dog by ' nocuous ' or harmfm stimuli
(such as a prick, a strong squeeze, chemical agents, or excessive
heat), or by electrical stimuli applied to the skin of the limb or of
any afferent nerve of the limb.
Sherrington has shown that when the legs of the animal are so
prepared that only the flexors can act on one knee, and only the
extensors on the other, stimulation of symmetrical points on the
two sides in the area of skin (receptive field) from which the flexion
reflex can be evoked causes contraction (excitation) of the flexors and
simultaneous relaxation (inhibition) of the tone of the extensors. The
same is true when corresponding afferent nerve-twigs are stimulated
on the two sides. From this it is inferred that each of the nerve-fibres
from the receptive field of the reflex divides in the cord into two sets
of end-branches (e.g., collaterals) — a set which produces excitation
when it is stimulated, and another set which produces inhibition.
Reversal of Reflexes. — The difference in action is specific in the
sense that no mere change in the kind or intensity of stimulation
affects it. Yet there are facts which show that the specificity is not
absolutely immutable, and that a change of conditions in the spinal
cord may permit excitation of a given group of muscles to be pro-
9o4 THE CENTRAL NERVOUS SYSTEM
duced by the stimulation of an afferent path which is primarily
inhibitory for them. One of the most striking illustrations of this
possibility is seen in the action of strychnine. Stimulation of the
internal saphenous nerve below the knee — say in a dog after removal
of the cerebrum — is known always to produce inhibition of tl.e
portion of the quadriceps extensor whose contraction causes the
knee-jerk.
If now the animal be poisoned by a small dose of strychnine,
stimulation of the nerve causes no longer reflex relaxation, but reflex
contraction of the muscle. This fact indicates that the essential
action of strychnine is something different from a mere reduction of
the resistance to the spread of impulses in the cord (Sherrington).
Tetanus toxin produces a similar effect, though more slowly.
The reversal of the depressor reflex on the blood- pressure has been
previously alluded to (p. 188). A different type of reversal, and one
of most interest in connection with the co-ordination of reflexes, is
illustrated by such observations as the following: The extensor
thrust is only obtained by the adequate form of stimulation de-
scribed on p. 901, when the hind-limb is in a condition of flexion.
When the leg is passively extended at the time when the stimulus is
applied, the response is not the extensor thrust, but flexion of the
leg and thigh (direct flexion reflex). The passive assumption of a
condition of flexion at the knee and thigh appears, accordingly, to
favour the extensor reaction (Sherrington). The observations of
Magnus have shown that such relations are general ; for example,
the reaction is usually extension when the opposite posterior limb
is flexed at the time of stimulation, and flexion when the opposite
leg is extended. In the spinal cat, stimulation applied to the tail,
especially near the root, elicits always a stroke towards the side on
which at the time of stimulation the muscles are extended. The
phenomenon is dependent upon the integrity of the afferent nerves
of the passively extended or flexed muscles whose position influences
the reflex, and of the afferent nerves of the tendons and fascia re-
lated to them. The condition of the reflex centres is in some way
influenced by impulses conducted along those afferent paths.
Not only is the tone of the extensors diminished or abolished
during the activity of the flexors, but the contraction of the knee
extensors evolved by striking the patellar tendon, which is called
the knee-jerk, either fails to appear, or appears but feebly, when the
flexion reflex is simultaneously elicited, even when the mechanical
antagonism of the flexor contraction has been eliminated by pre-
viously detaching the flexors from the knee.
The Knee-jerk. — This is sometimes termed a pseudo-reflex. For
certain authorities believe that the mechanism by which it is pro-
duced is different from that concerned in the reflex blinking of the
eyelid, or the reflex retraction of the testicle, or the drawing-up of
FUNCTIONS OF THE SPINAL CORD 9<>5
the foot when the sole is tickled. The knee-jerk is obtained in
undiminished strength when the nerves of the ligamentum patellae
have been divided. It is therefore not a reflex movement caused by
stimulation of afferent nerves coming from the tendon, and the name
' tendon-reflex ' is clearly a misnomer. But that it is related in some
way or other to afferent impulses is certain, for division of the
posterior roots that enter into the anterior crural nerve abolishes
the knee-jerk. The phenomenon, according to these authors who
deny that it is a true reflex, comes under the head of what is called
myotatic irritability — that is, it depends on mechanical stimulation
of the slightly-stretched muscle by the pull of the tendon when it is
struck. It is necessary for this stimulation that the muscle should
be to a certain extent tonically contracted. So that when the
afferent fibres are interrupted, or the grey matter of the cord dis-
organized, and the reflex tone abolished, the knee-jerk disappears.
The strongest objection to considering it an ordinary reflex is the
shortness of the interval which elapses between the tap and the jerk,
which, according to some observers, is not much greater than the
latent period of the quadriceps muscle for direct electrical stimula
tion, as measured under the ordinary conditions of its contraction.
There is no doubt that the interval is very brief, although somewhat
conflicting results have been obtained by different observers for the
corrected latency — that is, the period between stimulus and response
minus the latent period of the muscle. In man this period seems
to be about 0-02 second. In a dog with divided spinal cord the
interval was found to be 0-014 t° 0-02 second (Applegarth) ; in the
rabbit only 0-008 to 0-005 second (Waller and Gotch). Recent
observations in which the electrical response of the muscle as re-
corded by the string galvanometer was employed instead of the
contraction have yielded results not very different from those
obtained by the older methods, o-on to 0-015 second according to
Synder. Taking account of the newer observations on the velocity
of the nervous impulse (p. 793), it would appear that the interval is
not really too short to prevent the knee-jerk from being classified
as a true reflex contraction, although a very brief one.* The rein-
forcement of the knee-jerk is referred to under another heading
(p. 911). It is admitted that, in addition to the direct stimu-
lation of the muscle on the same side, the tendon-tap may cause
also a true reflex knee-jerk on the opposite side, the interval between
tap and contraction being about £ second.
Spread or Irradiation of Reflex Action. — As the strength of the
stimulus which has been evoking a given reflex movement is in-
creased, the reflex effect becomes more and more extensive, spreading
out or irradiating in various directions. If, for example, the reflex
* There is really now no good reason for regarding the knee-jerk as anything
else than a true reflex. The term pseudo-reflex and other terms implying
that the knee-jerk is not a reflex should therefore be dropped.
go6
in question is the flexion reflex elicited by stimulation of the plantar
surface of the hind-foot in the spinal animal, increase of the stimulus
will cause, in addition to flexion of the same hind-foot, extension of
the opposite hind-limb, then in the homonymous fore-limb (i.e., the
limb on the same side) extension at the elbow and retraction at the
shoulder, then certain definite movements, the details of which need
not detain us here, in the opposite fore-limb, and ultimately also
definite movements of the head and tail (Sherrington). Obviously
there is a certain orderliness in the spread of the reflexes; they
follow a certain regular march; the irradiation in the tangle of the
spinal paths is not an indiscriminate one. The same fact emerges
quite as clearly when other reflexes are studied in a similar way; and
certain laws or rules which define the spread of the impulses in spinal
reflexes have been deduced. For descriptive purposes, in dealing
with reflex action, it is convenient to consider each lateral half of
the cord as divisible into regions each related on the one hand to a
certain area of the receptive surface (skin), and on the other to
certain muscles. Such regions are those of the neck, including the
pinna (cervical), the fore-limb (brachial), the trunk (thoracic), the
hind-limb (crural), and the tail (caudal). According to their rela-
tion to these regions the spinal reflexes can be classified as ' short '
or ' long.' The short spinal reflexes are those in which the muscular
response takes place in the same region as the application of the
stimulus. The long reflexes are those evoked when the stimulus is
applied to the receptive field of one region, and the response occurs
in the musculature of another region. For the short reflexes
Sherrington has given a number of rules, which may be stated as
follows: (i) The closer together their spinal segments, the easier is
it for stimulation of a given efferent root to excite reflex contractions
of muscles supplied by a given afferent root. (2) For each afferent
root there exists in its own spinal segment (of course, on its own side
of the cord) a reflex motor path of as low a threshold (i.e., as easily
set into action) and of as high potency (i.e., producing as great a
reflex effect) as any open to it anywhere. It has been shown that
the afferent nerves of a skeletal muscle are derived from the spinal
ganglion corresponding to the segment of the cord containing its
motor cells. (3) Motor mechanisms for the skeletal musculature
lying in the same region of the cord, and in the selfsame spinal
segment, show markedly unequal accessibility to the local afferent
channels as judged by the reflex contractions produced. For
example, the reflex contraction of the flexors of the knee on the
stimulated side, and of the extensors of the opposite knee, is in
many animals much more easily elicited than contraction of the
extensors of the homonymous and the flexors of the contralateral
(i.e., opposite) side. This, however, is not because the last-named
extensors and flexors are really incapable of being reflexly affected
through the afferent fibres of the corresponding spinal segments, but
FUNCTIONS OF THE SPINAL CORD 907
because the reflex effect produced by them is in this case not con-
traction, but inhibition. (4) The groups of motor cells contempor-
aneously discharged by spinal reflex action innervate synergic
muscles (muscles which act in the same direction in effecting a
harmonious movement), and not antergic muscles (which antagonize
each other).
This disproves the old idea that the movements, caused by ex-
citation of an efferent spinal root, are co-ordinated synergic move-
ments, since at many joints the flexors and extensors both receive
motor fibres from one and the same root, and stimulation of the
root must simultaneously excite antagonistic muscles. ' The
collection of fibres in a motor spinal root does not represent a reflex
figure — i.e., a number of simple reflexes occurring simultaneously —
nor does the receptive field of a reflex correspond with the distribu-
tion of an afferent root.'
(5) It follows from (i), (2), and (4) that the spinal reflex move-
ment which can be elicited in and from any one spinal region will
exhibit much uniformity even when the exciting stimulus is applied
at different and distant points within the receptive field. The
flexion reflex of the hind-limb, e.g., will have the same general char-
acter— i.e., flexion of each of the three main joints — whatever part
of the surface of the limb is stimulated. Yet the flexion movement
will be strongest at the joint whose flexors are innervated by motor
cells situated in a spinal segment near the entrance of the afferent
fibres from the stimulated skin area.
For the long spinal reflexes it is less easy to deduce definite rules,
for they can be less easily and constantly evoked than the short
reflexes. The so-called laws of spread formulated by Pfliiger for
the long spinal reflexes, and based mainly on observations made
in the brainless frog and on clinical records in cases of spinal lesion
in man, need not be stated here. For Sherrington has shown that
they require serious modification. Especially is this true of Pfliiger's
fourth law, that the reflex irradiation spreads always more easily
up in the direction of the medulla oblongata, so that stimulation of
a fore-limb does not cause reflex contraction of a hind-limb, although
excitation of a hind-limb may cause movement of one or both fore-
limbs. This law does not hold in the mammal. As a rule, indeed,
irradiation takes place more easily down than up the cord. Excita-
tion of the skin of the pinna easily causes reflex movements of the
limbs, while the reverse is rare. Reflex movements of the hind-
limb in the spinal animal are more easily evoked by stimulation of
the fore-limb than movements of the fore-limb by stimulation of
the hind. It is easier for the irradiation to cross the cord from
hind-limb to hind-limb than to pass up from hind- to fore-limb;
but it is often easier for irradiation to occur down the cord from
fore- to hind-limb than across the cord from one fore-limb to the
other. Afferent channels from the skin of the shoulder, through
90S THE CENTRAL NERVOUS SYSTEM
which the scratch- reflex is discharged (in the dog), are freely con-
nected with efferent paths to the muscles of the hip, knee, and ankle
by an uncrossed path descending the lateral column (Sherrington),
In cats, after temporary occlusion of the cerebral circulation, which
throws the brain out of gear, it is easy to elicit movements of the
hind-legs by pinching the fore-paws or the skin of the upper part
of the body. The scratch-reflex can also be very readily evoked,
and in great intensity, by stimulating the pinna, and is not confined
to the side stimulated. In anaemia of the brain and (cervical) cord
and subsequent resuscitation, homolateral reflexes (i.e., on the
same side as the stimulus) are submerged later and emerge sooner
than contralateral reflexes whose centres lie in the area which was
rendered anaemic (Pike, Guthrie, and Stewart).
Co- Ordination of Reflexes. — The co-ordination or orderly combina-
tion of muscular actions for the production of appropriate and har-
monious movements is one of the most important functions of the
central nervous system. Both the brain and the cord take a share
in this co-ordination. The role of the brain will be considered later
on, but it is essential to recognize now that many of the movements
which the brain directs represent spinal reflexes already synthesized,
compounded, or co-ordinated in a very high degree. This is the
reason why, in the spinal animal, the inexperienced observer may
sometimes be startled by the apparently ' purposive character ' of
a reflex movement — the scratch-reflex in the dog or cat, e.g., or the
extensive reflex movements of the hind-legs of a brainless frog
when the skin is pinched or painted with dilute acid, so plainly
directed to the seat of irritation. When a drop of acid is applied
to the flank of such a frog, it will attempt to wipe it off with the
foot which is situated most conveniently. If this foot be held, it
will use the other. These reactions are necessarily purposive in
character, since they have been evolved with reference to the ad-
vantage of the organism as a whole. They are the sort of complex
reactions which the intact animal would have had to improvise
by the combination of a considerable number of simple movements
when it was executing such defensive reactions, with the conscious
purpose of escaping from the irritant, were they not already present
as purposive reflexes in the ready-made condition.
In the combining of reflexes we may distinguish between simul-
taneous combination — i.e., the combination of reflex actions taking
place at the same time — and successive combination — i.e., the
combination of reflexes in such a way that they follow each other
in an orderly sequence. The facts already mentioned in speaking
of irradiation afford a partial explanation of the co-ordination of
reflexes by simultaneous combination. The movements are orderly
and harmonious because the spread of the reflexes is not indis-
criminate, but follows a definite ' march,' determined partly by the
FUNCTIONS Of THE SPINAL CORD 909
anatomical relations of afferent and efferent paths, partly by the
varying resistance of the synapses or other structures whose proper-
ties fix the threshold value of the excitation by which an arc can be
forced. In general it is not enough that the channel of the final
common paths (p. 899) to the muscles whose contraction produces
the reflex movement should be thus open to the afferent arcs that
elicit the movement; they must be closed to other afferent arcs
which might disturb the reflex. Not only so: there is evidence
that very frequently the final common paths are, so to say, more
widely opened to the afferent arcs in question by the ' reinforcing '
or ' facilitating ' influence of allied, though it may be distant,
afferent arcs, which are simultaneously excited (p. 911). Further,
the final common paths to antagonistic muscles must also be
temporarily closed. The closing of these central connections, or
rather the raising of their threshold sufficiently to bar the impulses
from passing through the door, is an inhibitory phenomenon. Ex-
citation of the desired movements and inhibition of antagonistic
movements go hand-in-hand in the simultaneous combination of
reflexes. It is obvious that if a movement is to be efficiently exe-
cuted, it cannot be the result of a compromise between competing
reflexes. A segment of a limb can be either flexed or extended, but
cannot at the same time undergo both flexion and extension. In
the interests of an effective movement, one or the other must give
way utterly. The reflex which eventuaUy prevails makes a clear
field for itself by inhibiting all other reflexes which do not co-operate
with it. For example, if the receptive area of skin from which the
scratch reflex is elicited be stimulated and a painful stimulation be
at the same time applied to the foot, we do not obtain a mixed
scratch and flexion reflex, which would result in a confused and
ineffective combination of movements, but a pure scratch or flexion
reflex, as a rule the latter.
The successive combination of reflexes is well illustrated by the
contraction of the oesophagus in deglutition. First one portion of
the tube and then the next below are involved in the reflex action.
The combination consists in the orderly sequence. The manner in
which this is secured in this class of reflex action has been lumin-
ously discussed by Sherrington,* but details cannot be given here.
While only allied reflexes — i.e., such as mutually reinforce and
therefore harmonize with each other — can be simultaneously com-
bined, and antagonistic reflexes cannot, both allied and antagonistic
reflexes can be successively combined. An example of the succes-
sive combination of allied reflexes is the series of scratch reflexes
caused by a parasite travelling across the receptive field of the
reflex. An example of the successive combination of antagonistic
* ' Integrative Action of the Nervous System, ' to which work the advanced
student is referred.
910 TH£ CENfKAL tiEttVOtiS
reflexes is afforded when either the scratch reflex or the flexion
reflex is induced and caused to interrupt the other while it is pro-
ceeding. The transition — e.g., from flexion to scratch reflex — is
made without any period of confusion. Thus, if the scratch reflex
has been induced and is being executed, and the foot is then pain-
fully stimulated, the scratch reflex immediately ceases, and the
flexor reflex takes its place. When the flexor reflex has termin-
ated, the scratch reflex may be resumed. The same holds good for
other antagonistic reflexes. In many cases the avoidance of con-
fusion is due to the inhibition of the first reflex, or often to inhibition
of the set of muscles which were active in the first reflex combined
with excitation of their antagonists (so-called interference). It is
obvious that this is an adaptation of great importance.
Influence of the Brain on the Spinal Reflexes. — The spinal reflexes
can be influenced by impulses descending from the higher centres.
For (a) it is a matter of common experience that a reflex movement
may be to a certain extent controlled, or prevented altogether by an
effort of the will, and it is worthy of remark that only movements
which can be voluntarily produced can be voluntarily inhibited.
(b) Long-continued muscular contractions may be caused in animals
after removal of the cerebral hemispheres by stimulation of afferent
nerves — for example, by scratching the mucous membrane of the
mouth in a ' brainless ' frog or Necturus. (c) By stimulation of
certain of the higher centres reflex movements which would other-
wise be elicited may be suppressed or greatly delayed. If the
cerebral hemispheres are removed from a frog, and one leg of the
animal dipped into dilute acid, a certain interval, the (uncorrected)
reflex time, will elapse before the foot is drawn up (p. 996). If,
now, a crystal of common salt be applied to the optic lobes, or
corpora bigemina.or the upper part of the spinal cord, and the experi-
ment repeated, it will be found either that the interval is much
lengthened or that the reflex disappears altogether. Stimulation
of the optic lobes relaxes the reflex sexual embrace of the male frog
when it is present. From such experiments it has been concluded
that centres which can inhibit the spinal reflexes are situated in the
thalamus, the corpora bigemina and the medulla oblongata of the
frog. In mammals, also, there is evidence of the existence of
mechanisms in the brain, the excitation of which diminishes the
reflex excitability of the cord. For example, stimulation of the
frontal convolutions in the dog causes a diminution in the height
of reflex contractions of the limbs. Strong stimulation of an
afferent nerve may abolish or delay a reflex movement which is
being elicited through other receptors, (d) If such, inhibitory
mechanisms exist, it is to be supposed that elimination of the brain
will render it easier to elicit reflexes from the cord. Experiment
shows that this is actually the case. An animal like a frog responds
FUNCTIONS OF ftiE SPINAL CORD 911
to stimuli by reflex movements more readily after the medulla
oblongata has been divided from the spinal cord or the brain re-
moved. In the dog the scratch reflex is elicited more easily after
removal of the cerebral cortex or its elimination by cerebral
anaemia. In the guinea-pig, after extirpation of the cortex of one
hemisphere, the scratch reflex is more readily evoked on the side
of the lesion (Brown).
That the brain exerts more than a merely inhibitory influence on
the production of reflex movements is suggested by many facts.
The knee-jerk, for example, is increased or ' reinforced ' if an instant
before the tendon is struck the patient makes a voluntary movement
or is acted on by a sensory stimulus (Bowditch and Warren). In
health it varies in strength with many circumstances which affect
the activity of the central nervous system as a whole (Lombard,
etc.). It often disppears in pathological lesions, situated high up
in the cord in man, and is markedly impaired after high section of
the cord in dogs. In hemiplegia (paralysis of one side of the body,
caused by disease in the brain) the cutaneous reflexes on the para-
lyzed side may sometimes be absent for years. Some observers
have even gone so far as to say that under normal conditions the
so-called spinal reflexes are really cerebral — in other words, that
the afferent impulses run up to the brain and there discharge efferent
impulses, which pass down to the motor cells of the anterior horn
and cause their discharge. It may be admitted that there is no
physiological ground for supposing that the afferent impulses which
have to do with the reflex contraction of the muscles of the leg
when the sole is tickled, stop short at the motor cells of those spinal
segments from which the efferent nerves come off, while the af-
ferent impulses which have to do with the sensation of tickling pass
up to the brain. The probability is that under ordinary circum-
stances such afferent impulses pass up the cord in long afferent
paths, as well as directly towards the motor cells along those fibres
of the posterior roots and their collaterals which bend forward into
the anterior horn at the level of their entrance into the cord. And
the only question is whether, as a matter of fact, the spinal motor
cells are most easily discharged by the impulses that reach them
directly, or by the impulses that come down to them by the round-
about way of the brain, and the efferent fibres tiiat connect it with
the cord. It is evident that the answer to this question need not
be the same for all kinds of animals. It may well be that in the
higher animals, in which the cortex has undergone a relatively great
development, the spinal motor mechanisms are more easily dis-
charged from above than from below, while in lower animals the
opposite may be the case. When the cord is cut off from the brain
the afferent impulses may overflow more easily into the spinal motor
cells since their alternative path is blocked. In the frog, where
912 THE CENTRAL NERVOUS SYSTEM
there is already a beaten track between the posterior root-fibres
and the cells of the anterior horn, this overflow may be established
immediately after section of the cord, and may of itself lead to an
exaggeration of the reflexes. In animals like the dog a longer time
may be necessary before the unaccustomed route from the end
arborizations of the afferent axons and their collaterals to the
dendrites or the bodies of the motor cells becomes natural and easy ;
in man a still longer interval may be required. Moore and Oertel
have made a careful comparative study of reflex action after com-
plete section of the cord in the cervical or upper dorsal region, and
conclude that the spinal reflexes in the higher animals are far more
dependent on the upper portions of the central nervous system than
in the frog.
Spinal Shock. — The phenomena of spinal shock and its varying
severity in different animals may be accounted for by the rupture of
the paths normally used in the reflexes. The theory that the shock is
due to an inhibition set up by the mechanical injury is untenable. For
shock affects only the portion of the central nervous system distal (or
aboral) to the lesion. When a dog is allowed to live after transection
of the cord in the lower cervical region till shock has been recovered
from, a second transection distal to the first is followed by only slight
and very transient depression of the reflex power, although the direct
effect of the second injury ought, of course, to be as great as that of the
first. Finally, according to Sherrington, the condition of the spinal
reflex arcs in shock differs from the condition caused by inhibition, and
resembles rather a general spinal fatigue in which conduction along the
arc and especially across the synapses is difficult and uncertain. This
condition is supposed to be due to the loss of a ' tonic ' influence of
higher centres, assumed to be necessary for the maintenance of the
normal conductivity of the arc. These cranial centres, if they exist, or,
at least, the most efficient of them, must be assumed to be situated
distal to the cerebral cortex, probably in the pons or mid-brain. For
section just behind the pons causes much more severe shock than
removal of the cerebral hemispheres.
Peripheral Reflex Centres. — The question whether any reflex centres
exist outside of the spinal cord and brain, and especially in the sympa-
thetic ganglia, has been the subject of a lengthy controversy. That
the spinal ganglia cannot act as reflex centres is generally acknowledged,
and it is not difficult to see that, for anatomical reasons, this must be so.
A reflex arc must, so far as we know, in all highly -organized animals
include at least two neurons. There is no proof that an afferent
impulse can ascend an axon to a cell-body and there excite an efferent
impulse, which, descending the same axon in a separate set of fibrils,
gives rise to a reflex contraction, or a reflex secretion. Now, the cells
of a spinal ganglion represent the original neuroblasts from which the
posterior root-fibres grew out as processes towards the cord on the one
side and the periphery on the other. A sensory fibre passing into the
ganglion makes connection with a cell by a T-shaped junction and
passes on its course again. No afferent fibres run from the nerve-trunk
into the ganglion, to end in arborizations around the ganglion cells,
and no efferent fibres arise from nerve-cells in the ganglion to pass out
into the trunk. For although a slightly greater number of medullatcd
fibres of small calibre is found in a spinal nerve-trunk immediately
FUNCTIONS OF THE SPINAL CORD gi<5
distal to the junction of the roots than in both roots taken together, this
appears to be due to the passage into the nerve (from the grey ramus
communicans) of medullated fibres which end in the bloodvessels or
other tissue of the ganglion (Dale). Here it is evident that there is no
possibility of a complete reflex arc. Indeed, it is not certain that the
normal afferent impulses pass through the bodies of the spinal ganglion
cells at all. For (i) a negative variation can be observed in the posterior
roots above the ganglia on stimulation of the trunk of a fr jg's sciatic
nerve more than two days after the death of the animal, when the
ganglion cells may be supposed to have completely lost their vitality,
and when no reflex negative variation can be detected in the central
stump of a severed anterior root on excitation of the sciatic or the
corresponding posterior root. Such a reflex action current is normally
obtainable from a fresh preparation. (2) When the blood-supply of the
posterior root-fibres and the ganglion is cut off without killing the frog,
the nerve impulse is still conducted by the fibres, as is shown by the
reflex movements elicited on stimulation of the central end of the sciatic,
at a time when the nerve-cells show marked histological alterations.
(3) Prolonged excitation of the posterior roots or the mixed nerve causes
no noticeable microscopical changes in the ganglion cells (Stcinach).*
(4) The application of nicotine to a spinal ganglion does not hinder the
passage of impulses through the corresponding afferent fibres, if it
acts on spinal ganglion cells as it does on sympathetic ganglion cells
(p. 182), this must be because the impulses do not require to traverse
the ganglion.
Axon-Reflexes. — In the ordinary sympathetic ganglia,! also, it is
doubtful whether the anatomical foundation for a reflex arc exists, and
the most careful physiological experiments have failed to connect them
with any reflex function. Sokownin, indeed, observed that stimulation
of the central end of the hypogastric nerve caused contractions of the
bladder, and he considered these movements to be reflex, the centre
being the inferior mesenteric ganglion. Langley and Anderson have
also found that when all the nervous connections of the inferior
mesenteric ganglion, except the hypogastric nerves, are cut, stimulation
of the central end of one hypogastric causes contraction of the bladder,
the efferent path being the other hypogastric. In addition, they have
observed an apparent reflex excitation of the nerves which supply the
erector muscles of the hairs (pilo-motor nerves) through other sympa-
thetic ganglia. They believe, however, that in neither case is the action
truly reflex, but that it is caused by stimulation of the central ends of
motor fibres, which come off from the spinal cord, and in passing through
the ganglion give off collateral branches to some of its cells. In the
case of the inferior mesenteric ganglion the spinal fibres passing down
in the left hypogastric would send branches to arborize around ganglion
cells which give origin to fibres of the right hypogastric, and vice versa.
When the central end of the left hypogastric is stimulated the excitation
is conducted up the spinal fibres, and so reaches their branches, and,
through the ganglion cells, the sympathetic fibres of the right hypogastric,
which convey it to the muscles of the bladder (see sartorius or gracilis ex-
periment of kuhne, p. 792) . Other examples of such axon-reflexes exist.
* Hodge obtained changes. In such experiments it is necessary that the
ganglion should not be directly excited by electrotonic currents or escape of
the stimulating current.
f The ganglion cells of Auerbach's and Meissner's plexus in the intestine
are not of ordinary sympathetic type, and, as has been previously pointed
out, it is probable that they, or some of them, are true reflex centres for the
stomach and intestines.
58
9M THE CENTRAL NERVOUS SYSTEM
Reflex Time. — When a reflex movement is evoked, a measurable
period elapses between the application of the stimulus and the
commencement of the movement. This interval may be called the
uncorrected reflex time or the latent period of the reflex. A part of
the interval is taken up in the transmission of the afferent impulse
to the reflex centre, a part in the transmission of the efferent impulse
to the muscles, a part represents the latent period of muscular
contraction, and the remainder is the time spent in the centre, or
the true reflex time. Ordinarily this time, though absolutely short,
is relatively so great that the total latent period of a reflex is much
longer than when a similar length of nerve-trunk is interposed be-
tween the point of application of the stimulus and the muscle.
When the conjunctiva or eyelid is stimulated on one side both eye-
lids blink. This is a typical reflex action reduced to its simplest
expression, and the true reflex time is correspondingly short — only
about Jff second (50 a*). An additional T^y second (10 a-) is con-
sumed in the passage of the afferent impulse along the fifth nerve
to the medulla oblongata, of the efferent impulse from the medulla
to the orbicularis palpebrarum along the seventh nerve, and in the
latent period of the muscle. When a naked nerve, like the sciatic,
is stimulated, the true reflex time is reduced to y^ to -^ second. As
estimated by Tiirck's method (p. 996), the uncorrected reflex time
is greatly lengthened, it may be to several, or even many, seconds.
For here it is evident that the time taken by the acid to soak
through the skin and reach the nerve-endings in strength sufficient
to stimulate them is included. But even when the peripheral
factors remain constant, the central factor may vary. With strong
stimulation, e.g., the reflex time is shorter than with weak stimula-
tion. With weak stimuli the latent period of the flexion reflex in
the dog is usually 60 a- or 120 a-. It may even be as long as 200 a.
With strong stimuli it may be as little as 30 cr. Even 22 a has been
seen, which is little more than for nerve-trunk conduction. Fatigue
of the nerve-centres delays the passage of impulses through them ;
and strychnine, while it increases the excitability of the cord, also
lengthens the reflex time.
Reflexes in Disease. — In order that a reflex action may take place,
the reflex arc — afferent nerve, central mechanism, and efferent nerve —
must be complete; and, in fact, a whole series of simple reflex move-
ments exists, the suppression, diminution, or exaggeration of which
can be used in diagnosis as tests of the condition of the reflex arc. It
is customary to divide these into superficial reflexes, elicited from
receptive fields on the, surface of the body (extero-ceptive fields), and deep
reflexes, elicited from receptors in the depth of the organism (proprio-
ceptiue fields), especially in the muscles and the tendons and joints con-
nected with them. The extero-ceptive reflexes are normally excited
by extraneous stimuli acting on the surface from the environment.
The proprio-ceptive reflexes are normally excited by changes (muscular
* r>rl *" the brain, two ipternal carotids
and two verteBrals. The vertebrals unite at the base of the Skull* to
form the~single mesial basilar artery, which, running forward in- a groove
in the occipital bone, splits into the two posterior cerebral arteries.
Each carotid, passing in through the carotid foramen, divides into a
middle and an anterior cerebral artery; the latter runs forward in the
great longitudinal fissure, the former lies in the fissure of Sylvius. A
communicating branch joins the middle and posterior cerebrals on each
side, and a short loop connects the two anterior cerebrals in front. In
this way a hexagon is formed at the base of the brain, the so-called
circle of Willis. While the anastomosis between the large arteries is
thus very free, the opposite is true of their branches. All the arteries
in the substance of the brain and cord are ' end-arteries ' — that is to
say, each terminates within its area of distribution without sending
communicating branches to make junction with its neighbours. The
consequence of these two anatomical facts is: (i) that interference with
the blood-supply of the brain between the heart and the circle of Willis
does not readily produce symptoms of cerebral anaemia; (2) that the
blocking of any of the arteries which arise from the circle or any of their
branches leads to destruction of the area supplied by it. Nearly, all
dogs recover after ligation in one operation of both carotids and both
vertebral arteries. In monkeys both carotids may, as a rule, be safely
tied, and one carotid in man. If, in addition to the two carotids, one
vertebral be ligated at the same time in the monkey, sopor results, and
this is generally followed by extensor rigidity, coma, and death in
twenty-four hours. In one case a monkey survived this triple ligation,
but became demented. The motor paralysis and rigidity were much
greater than in the dog. In the condition of partial anaemia the cortex .
is more excitable than normal, but the excitability disappears at once
when the anaemia is rendered complete (Hill).
The basal ganglia are fed by twigs from the circle of Willis and the
beginning of the posterior, middle, and anterior cerebral arteries. Of
these the most important are the lenticulo-striate and lenticulo-optic
branches of the middle cerebral, which are given off near its origin, and
run through the lenticular nucleus into the internal capsule, and thence
to the caudate nucleus and optic thalamus respectively. The chief part
of the blood from the circle of Willis is carried by the three great cerebral
arteries over the cortex of the brain. The white matter, with the
exception of that in the immediate neighbourhood of the basal ganglia,
is nourished by straight arteries which penetrate the cortex. The
middle cerebral supplies the whole of the parietal as well as that portion
of the frontal lobe which lies immediately in front of the fissure of
Rolando and the upper part of the temporal lobe. The rest of the
990 THE CENTRAL NERVOUS SYSTEM
frontal lobe is supplied by the anterior cerebral, and the occipital lobe,
with the lower part of the temporal lobe, by the posterior cerebral.
The medulla oblongata, cerebellum, and pons are fed from the verte-
brals and the basilar artery before the circle of Willis has been formed.
Resuscitation of the Central Nervous System after Total Anaemia.
— Complete temporary anaemia of the brain and upper cervical
cord can be produced in most cats by passing temporary ligatures
around the innominate artery and left subclavian proximal to
the origin of the vertebral artery. Artificial respiration is main-
tained through a tube passed through the glottis. The eye reflexes
disappear very quickly, and a period of high blood-pressure imme-
diately follows the occlusion. A fall of pressure succeeds, due to
vagus inhibition of the heart, and this is followed by a second rise
after the vagus centre succumbs to the anaemia. Respiration stops
temporarily (in twenty to sixty seconds) after occlusion; then
follows a series of strong gasps, and finally cessation of all respiratory
movements. The blood- pressure slowly falls to a level which is then
maintained approximately constant for the remainder of the occlu-
sion period. The anterior part of the cord and the encephalon lose
all function; no reflexes can be elicited from this part of the central
nervous system. The intra-ocular tension is much reduced, and the
cornea is characteristically wrinkled.
When the cerebral circulation is restored by releasing the vessels,
the general arterial pressure soon begins to rise if the period of
occlusion has not overstepped the limit of successful cardio- vascular
resuscitation. The respiration returns suddenly, the time of
return depending on the length of the occlusion and on other factors.
The respiratory rate, at first slow, soon becomes normal, and then
more rapid than normal. The eye-reflexes reappear more gradu-
ally; the intra-ocular tension increases, and the shrunken cornea
becomes smooth and hard. The anterior part of the cord recovers
its functions gradually; the reflexes connected with it return, first
the homonymous, then the crossed. A short period of quiet follows ;
then spasms of the skeletal muscles appear, gradually increase in
severity and extent, and terminate in (a) death, (b) partial, or
(c) complete recovery. In partial recovery, disturbances of loco-
motion, such as walking in a circle, paralysis, apparent dementia
or loss of intelligence, and loss of sight or hearing, may be observed.
Voluntary movements of the head, neck, shoulders, and fore-limbs
have been seen eight minutes after release from an occlusion of six
minutes. Blindness has been observed without loss of the pupillary
light reflex. In this case the visual cortex would seem to have
suffered more than the lower centres, an illustration of a general
rule. Complete recovery is rare after total anaemia lasting as much
as fifteen minutes, and has not been observed after an anaemia of
twenty minutes. Ten to fifteen minutes of total anaemia represent
CHEMISTRY OF NERVOUS ACTIVITY 991
the limit beyond which recovery of the brain, and therefore successful
resuscitation of the animal, cannot be expected.
Chemistry of Nervous Activity. — Of this we are practically ignorant.
The percentage composition of the solids and the percentage of
water in the brains of three persons of different ages are ex-
hibited in the following table (W. Koch) :
Child 6 Weeks
Child 2 Years
Adult 19 Years
(Brain 640 Grms.).
(Brain 1,100 Grms.).
(Brain 1,670 Grms.).
Whole Brain.
Grey.
White.
Whole
Brain.*
Grey.
White.
Whole
Brain, t
Proteins
46-6
48-4
31-9
40-I
47-1
27-1
37'i
Extractives . .
12-0
10-0
5'9
8-0
9-5
3'9
6-7
Ash
8-3
5-8
3'2
4'5
5'9
2-4
4'i
Lecithins and
kephalins . .
24-2
24-7
26-3
25-5
23-7
31-0
27-3
Cerebrins
69
8-6
17-2
12-9
8-8
1 6-6
12-7
Lipoid S as SO4
O-I
O-I
o-5
0-3
O-I
o-5
0-3
Cholesterinf
1-9
2 '4
15-0
8-7
4'9
18-5
n-7
Water
88-78
84-49
76-45
80-47
83-17
69-67
76-42
The next table shows the variations in the content of water,
solids, and protein in different parts of the nervous system (Halli-
burton) :
•
Water.
Solids.
Percentage of Pro-
teins in Solids.
Cerebral grey matter
83-5
l6-5
51
Cerebralwhite matter
69-9
30-1
33
Cerebellum
79-8
2O-2
42
Spinal cord as a whole . .
Cervical cord
71-6
72-5
28-4
27'5
31
3i
Dorsal cord
69-8
30-2
28
Lumbar cord
72-6
27-4
33
Sciatic nerves
65-1
34'9
29
The grey matter of the cerebrum in the adult contains 81 to
86 per cent, of water, the white matter 68 to 72 per cent., the
brain as a whole 81 per cent., the spinal cord 68 to 76 per cent.,
and the peripheral nerves 57 to 64 per cent. In the foetus more
water is present (92 per cent, in the grey and 87 per cent, in the
white matter).
The superior richness of the grey matter in proteins and the
preponderance of water in it are the chief chemical peculiarities
which distinguish it from the white matter. That it should have
* Calculated. f Calculated by difference.
992 THE CENTRAL NERVOUS SYSTEM
a high protein content is easily understood, for the protoplasmic
structures, the nerve-cells, are situated in the grey matter. But
that the most important functions should have their seat in a tissue
containing only 14 to 19 per cent, of solids is surprising, and should
warn us that the water is no less significant a constituent of living
• matter than the solids, and that it is not the mass of the solid
substances in a tissue which is the essential thing, but the whole
colloid complex, which cannot be constituted without the water.
Fresh nervous tissues are alkaline to litmus, but become acid
soon after death. No change of reaction has been detected during
activity.
That oxygen is used up during cerebral activity is certain, and
when the brain is coloured with methylene blue, by injecting it
into the circulation, any spot of it which is stimulated loses the
blue colour, the pigment being reduced. But if the animal is so
deeply narcotized that it does not respond to stimulation, the change
of colour does not occur.
Cholin (p. 366), a substance which can be derived from lecithin,
is believed to represent one of the waste products of nervous activity.
Exceedingly small traces of it are present in normal cerebro-spinal
fluid, and in certain diseased conditions of the brain, as in general
paralysis, the quantity is said to be notably increased, indicating
an increased decomposition of lecithin. The fatty acid constituent
of lecithin is liberated in degenerating nerve, giving rise to the
reaction with osmic" acid (p. 797). Some writers assert that this
increase in the cholin can be used as a test to distinguish organic
nervous disease from that which is purely functional. But the
matter is in dispute.
Cerebro-spinal Fluid. — The cerebro-spinal fluid, which fills the
ventricles of the brain and the central canal of the cord, is con-
tinuous with that contained in the subarachnoid space through the
foramen of Magendie, an opening in the piece of pia mater that helps
to roof in the fourth ventricle. It is secreted in part by the cubical
cells covering the choroid plexus, a fold of pia mater which projects
into each lateral ventricle. Extracts of choroid plexus, when in-
jected intravenously, increase the rate of secretion.
This action is dependent upon the presence of some substance in
the choroid plexus, which, however, is not a specific product of the
activity of the plexus, since extracts of the brain produce the same
effect. It may therefore be some product of the metabolism of the
brain which passes to the choroid plexus and stimulates secretion
by the epithelium. The substance is removed from the fluid by
filtration through a Chamberland filter, and is therefore probably
of high molecular weight. It is probable that variations in the rate
of secretion of the cerebro-spinal fluid by the choroid plexus are more
influential in governing the intracranial pressure than variations in
CEREBRO-SPINAL FLUID
993
the arterial and venous pressures. The idea that the cranial contents
constitute a fixed quantity, without the power of contraction or
expansion, can no longer be maintained (Dixon and Halliburton).
A graphic record of the rate of secretion of the cerebro-spinal fluid
in the dog may be obtained by inserting a hollow needle through the
occipito-atlantoid ligament into the great subarachnoid cistern,
and allowing the liquid to fall upon a drop-counter writing on a
drum (Fig. 399). It is not always possible, however, to be certain
by this method that the rate at which the fluid escapes represents
Fig. 399. — Influence of Extract of the Posterior Lobe of the Pituitary upon the Flow
of Cerebro-Spinal Fluid through a Hollow Needle inserted into the Cisterna
Magna through the Occipito-Atlantoid Ligament in a Dog. The animal was
anaesthetized by a constant method, insufflation of ether into the trachea. The
uppermost curve is respiration; the next, drops of cerebro-spinal fluid; the next,
arterial blood pressure; the fourth, signal line showing the point at which 50 mg.
of a dried extract of posterior lobe was injected into a vein. The signal line is
also the zero of blood pressure. The bottom trace is the time in seconds (Weed
and Cushing).
accurately the rate at which it is formed. A more exact method
appears to be the introduction of the needle into the third ventricle
(Fig. 400).
Cerebro-spinal fluid can easily be obtained in man by lumbar
puncture with a hypodermic needle sufficiently long to enter the
subarachnoid space in the spinal canal. The point usually selected
for the puncture is between the fourth and fifth lumbar vertebrae.
The normal pressure of the fluid is such that it trickles out by drops,
but in disease it is sometimes so high that it spurts out in a steady
stream. An examination of the fluid, especially for leucocytes or
bacteria, is of great diagnostic value in certain conditions. Nor-
mally it is a thin, clear, watery fluid, faintly alkaline in reaction
63
994
THE CENTRAL NERVOUS SYSTEM
to litmus, and with a specific gravity of about 1004 to 1007. It
contains the ordinary salts, but more potassium than sodium, unlike
other body fluids; a very small amount of protein (globulin) —
usually about o-i per cent. — and a little dextrose (Nawratzki).
Its composition is evidently different from that of ordinary lymph.
Only a few lymphocytes are present in health, but in some diseases
(as in general paralysis of the insane, tabes, and cerebro-spinal
syphilis) a marked increase occurs. In acute cerebro-spinal menin-
gitis numerous polymorphonuclear leucocytes are found, which are
absent from the normal fluid.
The depression of the freezing-point (A) usually lies between
0-60° and 0-65° C. In a case of hydrocephalus it was 0-65° C.
Normally, cerebro-spinal fluid ,is somewhat hypertonic to the blood-
Fig. 400. — Sagittal Section of Dog's Skull, showing the Needle introduced into Third
Ventricle to tap Cerebro-Spinal Fluid (Weed and Gushing).
serum. In injury of the cribriform plate of the ethmoid bone and
also in some cases where there is no traumatic injury, the fluid
escapes from the nose, and the rate of its formation can thus be
ascertained. In one case it was found to be as much as 2 c.c. to
nearly 4 c.c. in ten minutes.
PRACTICAL EXERCISES ON CHAPTER XVI.
i. Section and Stimulation of the Spinal Nerve-Roots in the Frog. — (a)
Select a large frog (a bull-frog, if possible). Pith the brain. Fasten
the frog, belly down, on a plate of cork. Make an incision in the middle
line over the spinous processes of the lowest three or four vertebrae,
separate the muscles from the vertebral arches, and with strong scissors
open the spinal canal, taking care not to injure the cord by passing the
blade of the scissors too deeply. Extend the opening upwards till two
PRACTICAL EXERCISES 995
or three posterior roots come into view. Pass fine silk ligatures under
two of them, tie, and divide one root central to the ligature, the other
peripheral to it. Stimulate the central end, and reflex movements will
occur. Stimulate the peripheral end ; no effect is produced. Now cut
away the exposed posterior roots and isolate and ligature two of the
anterior roots, which are smaller than the posterior. Stimulate the
central end of one : there is no effect. Stimulation of the peripheral end
of the other causes contractions of the corresponding muscles.
(b) Stimulation of the roots may be repeated on the mammal, using
the dog employed for the experiment on the motor areas (p. 1001).
PJace tue animal, belly down, and insert a good-sized block of wood
between it and the board at the level of the lumbar vertebrae of the
spine. Divide the skin and muscles on either side of this region till the
laminae of the vertebrae are exposed. Snip through them with strong
forceps, and open the spinal canal, exposing a length of cord correspond-
ing to three or four vertebras. Ligate and stimulate the roots as in (a).
2. Reflex Action in the ' Spinal ' Frog. — Pith the brain of a frog,
destroying it down to the posterior third of the medulla oblongata.
(i) Note the position of the limbs immediately after the operation, and
again thirty to forty minutes later. Its hind -legs possess tone, and are
drawn up against the flanks. The animal can still execute certain
co-ordinated movements — e.g., pulling away its leg if a toe is pinched.
The power of maintaining equilibrium is lost. If placed on its back, it
lies there. When thrown into water it sinks usually without any
attempt at swimming. Verify the following facts, using mechanical
stimulation (pinching the toes or skin of the leg) : (a) If the stimulus
provokes muscular movements only on one side of the body, this is
usually on the same side as the stimulated point, (b) When the stimulus
causes reflex movements on both sides of the body, the stronger con-
tractions are on the side to which the stimulus was applied.
Determine whether it is easier to obtain movement of a portion of the
body innervated from a region of the cord above the level of the stimu-
lated nerves or below that level.
(2) With electrical stimuli (using a coil arranged for single shocks de-
termine if reflex movements are elicited by a single induced shock ap-
plied to the skin. Verify the fact that a series of shocks is more efficient,
the effects of the separate stimuli being summated in the reflex centres.
(3) To test the effect of thermal stimuli, dip the leg into a beaker of
warm water. Vary the temperature of the water, using a .series of
beakers with water at io°C., I5°C., 2O°C., etc., above the temperature of
the room. Place the leg for a moment in each, and determine which is the
most efficient stimulus. Immediately on withdrawing the leg from each
of the hot-water beakers immerse it in a beaker of water at room tem-
perature. Finally, dip the leg into a beaker of cold water, and heat it
gradually to a temperature at which a reflex was previously obtained.
Probably it will not be elicited by the gradual warming.
(4) ' Purposive ' Movements. — Touch the skin of one thigh with blot-
ting-paper soaked in strong acetic acid. The leg is drawn up, and the
foot moved as if to get rid of the irritant. If the leg is held, the other
is brought into action. Immerse the frog in water to wash away the acid .
(5) Spread (Irradiation) of Reflexes.— Gently stimulate a toe or a small
spot on the flank with weak induction shocks or weak mechanical
stimuli, and note the reflex effect obtained. Then go on gradually
increasing the strength of stimulation without increasing the area of
the field stimulated, and observe the extent and order of spread of the
reflex movements.
3. Reflex Time. — Pass a hook through the jaws. Holding the frog by
996 THE CENTRAL NERVOUS SYSTEM
the hook, dip one leg into a dilute solution of sulphuric acid (0-2 to
0*5 per cent.), and note with the stop-watch the interval which elapses
before the frog draws up its leg (Tiirck's method of determining the
reflex time). Wash the acid off with water.
Determine how the reflex time varies with the strength of the stimulus.
This can be done by using various strengths of acid. The reflex time
will be shorter the stronger the stimulus up to a certain point. Compare
the reflex time of movements on the same side of the body as the point
of application of the stimulus and on the opposite side.
4. Inhibition of the Reflexes. — (i) Destroy the cerebrum of a frog.
Dip one leg into dilute sulphuric acid as in 3, and estimate the reflex
time. Then apply a crystal of common salt to the upper part of the
spinal cord. If the opening made for pithing the frog is not large enough
to enable the cord to be clearly seen, enlarge it. Again dip the leg in
the dilute acid. It will either not be drawn up at all, or the interval will
be distinctly longer than before.
(2) Expose the viscera, including the heart, taking care not to injure
the cardiac nerves. Tap the intestines sharply with the handle of a
scalpel many times in succession. The heart is inhibited.
(3) Tie strings tightly around both fore-legs of a normal frog. Place
the animal on its back; it does not turn over. The hind -legs may be
pulled about in various ways without the frog turning over into its
normal position. The reactions concerned in the maintenance of
equilibrium are inhibited. Remove the strings. The animal cannot
be made to lie on its back except by force.
5. Spinal Cord and Muscular Tonus. — Destroy the brain of a frog.
Isolate the gastrocnemius, and cut away the bone below the knee.
Isolate the sciatic nerve without injuring it. Remove the muscles from
the femur, cut the bone and fix it in a clamp for graphic recording.
Connect the tendon with a lever, weighted with 5 to 10 grammes. Take
a base line. Destroy the spinal cord, or cut the sciatic and again take
a base line. The length of the muscle is slightly altered.
6. Spinal Cord and Tonus of the Bloodvessels' — Destroy the brain of
a frog. Arrange the web of the foot on the stage of a microscope, and
note the calibre of the bloodvessels in the field. Destroy the cord, and
observe the change in their calibre. They will dilate.
7. Action of Strychnine. — Pith a frog (brain only). Inject into one of
the lymph-sacs three or four drops of a o-i per cent, solution of strych-
nine. In a few minutes general spasms come on, which have inter-
missions, but are excited by the slightest stimulus. The extensor
muscles of the trunk and limbs overcome the flexors. Destroy the
spinal cord; the spasms at once cease, and cannot again be excited.
8. Mammalian Spinal Preparation (Sherrington).* — Deeply anaes-
thetize a cat with ether. Insert a cannula into the trachea (p. 202), and
continue the anaesthesia through this. Expose and ligate both common
carotids. Make a transverse incision through the skin over the occiput,
and extend it laterally behind the ears. Pull back the skin so as to
expose the neck muscles at the level of the axis vertebra. Feel for the
* A similar preparation can be used for certain experiments on the circu-
lation (Crile, Guthrie). For these, as well as for the study of many reflexes,
a good preparation is obtained by occlusion of the cerebral blood-supply in cats
(without decapitation). Even a human 'spinal preparation' is capable of
executing reflex movements. The Turkomans are stated to have decapitated
their prisoners and immediately placed on the neck a hot metal plate, which
sealed up the cut vessels. The (reflex) movements, which are described as very
lively, were then watched with an interest, it is to be supposed, not wholly
scientific.
PRACTICAL EXERCISES 997
ends of the transverse processes of the atlas, and divide the muscles
down to the bone just behind these processes. Now start artificial
respiration (p. 202), or sooner if necessary. Notch the spinous process
of the axis with bone forceps. Pass a strong thick ligature by a sharp-
ended aneurism needle close under the body of the axis, and tie it tightly
in the groove left by the incision behind the transverse processes of the
atlas and the notch made in the spinous process of the axis. This com-
presses the vertebral arteries where they pass from transverse process
of axis to transverse process of atlas. Pass a second strong ligature
under the trachea at the level of the cricoid cartilage and include in it
the whole neck, except the trachea, but at present only tie a single loop
on it. Now decapitate the animal with a large knife (an amputating
knife) passed from the ventral aspect of the neck through the occipito-
atlantal space, severing the cord just behind its junction with the bulb.
At the moment of decapitation tighten the ligature round the neck and
complete the knot. Destroy the head. If there is oozing of blood from
the vertebral canal, arrest it by raising the neck somewhat above the
level of the body. The carcass must be kept warm by placing it on a
metal box or table containing hot water, and the air used for artificial
respiration must also be warmed, as by passing it through a coil of
rubber tubing immersed in a water-bath which is kept hot. Stitch the
skin-flaps together so as to cover the cut end of the spinal cord and the
other structures cut in decapitation. By this procedure the spinal cord
is usually severed about 4 millimetres behind the point of the calamus
scriptorius. Although the blood-pressure remains low, reflexes employ-
ing the skeletal muscles can be fairly well elicited for hours. Study on
the preparation the reflexes described in the text (pp. QOI, 904) — e.g., the
flexion reflex of the hind and fore limb, as elicited from the skin, or one
of the afferent nerves of the limb — the crossed extension reflex of hind
and fore limb, the scratch reflex.
(1) Scratch Reflex. — (a) Evoke the reflex by rubbing the skin of the
neck behind the pinna. The scratching movements are in the hind-leg
of the same side. • Record them on a drum, on which is also written a
time-tracing in seconds. The record can be obtained by tying a piece
of tape, not too tightly, round the foot, leg, or thigh, and connecting
this by a thread with a lever. The thread is passed over a pulley below
the lever, so that its pull may be exerted at right angles to the axis of
rotation of the lever. The lever is attached to a light spring or a rubber
band, which is stretched when it moves in one direction, and in recoiling
brings it back again to its position of rest at the end of the contraction.
If the reflex is not easily evoked, it can be facilitated by producing a
slight degree of asphyxia by temporarily clamping the respiration tube.
Some time must elapse after the decapitation before a fair scratch reflex
can be expected. It is usually sufficiently well marked within an hour.
(6) While the reflex is occurring, stimulate with an interrupted current
the central stump of the popliteal nerve of the opposite hind-limb.
The scratch reflex may be cut short by inhibition. Also, during the
stimulation of this nerve the reflex may be incapable of being elicited
till the excitation of the inhibitory afferent nerve is stopped.
(2) Flexion Reflex. — (a) Stimulate with a weak interrupted current
the skin of some part of the hind-limb — say one of the toes. The flexion
reflex of the hind-limb on the same side may be evoked — i.e., a flexion
movement at the knee, hip, and ankle. Record the movements of one
of the joints or of flexor muscles after severing them from their insertion.
(b) Stimulate with a weak interrupted (faradic) current the central
stump of one of the nerves of a hind-limb — say the peroneal nerve.
The flexion reflex of the same limb may be elicited. Record the move-
gg8 THE CENTRAL NERVOUS SYSTEM
ments. Now produce temporary asphyxia by clamping the respiration
tube, and repeat the stimulation at half-minute intervals. The reflex
will be increased by the asphyxia. Do not interrupt the respiration for
more than two or three minutes, and immediately start it if the heart,
which can be felt through the chest, begins to weaken.
(3) Elicit the knee-jerk, as described in the text (p. 904). It is
generally exaggerated.
(4) By the unipolar method (p. 951) stimulate with a point electrode
one lateral half of the cross-section of the cervical cord exposed in
decapitation. The large electrode is placed on a shaved part of a fore-
arm. Various effects may be elicited according to the point of the
cross-section stimulated — e.g., stepping and scratch movements of the
hind-limbs. Other facts mentioned in the text in regard to spinal
reflexes can be verified on this preparation.
9. Decerebrate Cat Preparation (Miller and Sherrington) . — This
preparation, which must be made by the demonstrator, differs from
the spinal preparation described in 8, in that the plane of the section
is considerably higher, passing through the posterior part of the mid-
brain ' entering the posterior colliculi (posterior corpora quadrigemina)
near their hinder end and emerging about a millimetre anterior to the
front edge of the pons.' Many reactions can be conveniently studied
on this preparation, some of which cannot be obtained with the spinal
preparation. The respiratory movements usually go on without inter-
ruption, and reflexes whose centres are situated in the bulb, such as
the swallowing reflex, can be elicited. The circulation is well main-
tained, and the preparation can be used for a number of the experi-
ments given after Chapters III. and IV.
Under deep anaesthesia (chloroform and ether), the carotids are
temporarily clamped opposite the uppermost tracheal cartilage, and
the cat is then placed on the decerebrator (Fig. 401) in the prone posi-
tion, with its neck on the upper edge of the neck-block.
The interparietal suture is exposed by an incision through the scalp
from beyond the coronal in front to the lambdoid ridge and supraocci-
pital protuberance behind. A distance of 30 millimetres is then
measured off from the coronal suture backward along the interparietal
and the point is marked by notching the longitudinal median ridge of
bone. The head is placed between the prongs of the yoke with the
tongue-guard of the yoke-plate inside the mouth above the tongue,
which it protects. The chin lies in the hollow of the yoke under the
yoke-plate, the lower canines covered by the plate. The pelvis lies
on the pelvic platform, P, the hind limbs hanging freely. The head
is pushed down, the tongue guard in the mouth, until the embayed end
of the yoke-plate on either side of the tongue-guard meets the anterior
edge of the coronoid process of the lower jaw. The hook attached
to the leather cord is fixed in a loop of string previously tied trans-
versely through the upper lip, and the snout is drawn firmly down by
the cord, securing the head in position. The cord is fastened to a
elect on the under surface of the neck-block. The nose-piece is now
slid up so as to engage and support in its notch the apex of the muzzle,
and is fixed by the screw-clamp. A knife consisting of a planing-blade
mounted in a wooden handle is used for the de cerebration.*
* The blade is 12-5 centimetres wide, 9 centimetres high, and 4 millimetres
thick. It is bevelled on one face, the bevelled edge being 2 centimetres deep.
The cutting edge does not extend the whole width of the blade, but stops short
at 1*5 centimetres from each lateral edge. The mid-width of the blade is
marked by an engraved line on the front of the knife.
PRACTICAL EXERCISES 99$
The operator, standing on the left side of the animal, applies the mid-
point of the sharp edge of the blade, bevelled side forward, to the
point notched in the interparietal ridge, the width of the blade being
kept truly at right angles to the median plane of the head. The knife
thus held in the left hand is kept vertical, or nearly so, and is directed
so that the plane of the blade if continued downward through the
Fig. 401. — Cat Decerebrator (Miller and Sherrington). N, wooden neck- block,
mounted firmly on a strong base-board. N is inclined at 22° to the vertical
and supported by two stout wooden props meeting it somewhat below its top
at an angle of 44°. The top edge of the neck-block (cut at right angles to the
face of the block) is therefore at an angle of 22° to the horizontal. Y, yoke, a
Y-shaped fork of wood with one of the prongs projecting 6 centimetres beyond
the top of the neck-block, the other prong truncated nearly to its base. A
Y-shaped steel plate (the yoke-plate) is screwed to Y. It is shaped somewhat
like the wooden yoke, but its two side prongs are of equal length, and between
them projects a shorter prong, T, the tongue-guard. S is a T-shaped wooden
nose-piece, adjustably attached to the front of the steel-covered yoke. In the
upper border of the cross-piece of the T, is a V-shaped notch. A slot in the stem
of the T allows the T-block to be slid up or down on the steel yoke-plate, and
it can be fixed at any position by a thumb-screw. C, a leather cord passing
through a hole piercing neck-block, yoke and yoke-plate. The top end of the
cord, issuing from the hole in the mid-line of the yoke-plate, carries a short
Strong hook. The point of the notch in the nose-piece slides up to and slightly
beyond this hole. P, a light single-pillared platform, somewhat saddle-shaped
at the top, which can be slid on the baseboard nearer to or farther from the
neck-block.
head would meet a horizontal line engraved on the side-prongs of the
yoke-plate. This line is at the level of the free end of the tongue-
guard. A light blow is then struck with a mallet on the top of the
handle of the knife, sufficient to engage the edge in the skull in the
proper direction — i.e., toward the horizontal line on the metal plate.
Then with a couple of heavier blows the head is severed in the desired
plane.
iooo THE CENTRAL NERVOUS SYSTEM
The preparation is then removed from the apparatus, the neck being
held laterally behind the wings of the atlas to control the vertebral
arteries. It is placed on the experiment table with the neck well raised
by a string passed through the skin over the occiput, to restrain any
haemorrhage. Some cotton is packed across the cut surface of the mid-
brain. Bleeding soon ceases, and in two or three minutes one carotid
can be undamped, arteries in the masseteric regions being tied if neces-
sary. In two minutes more the clamp can be removed from the other
carotid.
10. With the preparation described in 9, study the swallowing reflex,
evoked — e.g., by the application of water by drops to the pre-epiglotti-
dean sinus between the base of the tongue and the epiglottis, or by
allowing water to drop into the pharynx. Dilute alcohol (one part of
ethyl alcohol added to four parts of water) is even more effective
than water; oil much less effective.
n. Reflex Postural Tonus (Decerebrate Rigidity). — Study the dis-
tribution of the tonus in the decerebrate cat prepared as in 9 — e.g.,
in the extensor muscle of the knee (the vasto-crureus), the gastrocne-
mius, semimembranosus, triceps, supraspinatus, etc. Isolate the knee
extensor by paralyzing all the other muscles of both hind limbs by nerve
section. The vasto-crureus still maintains its postural reflex contrac-
tion. To observe the right vasto-crureus place the animal on its left
side. Begin with the knee nearly at full extension and determine what
weight, attached to the tibia and pulling it backward by a cord fastened
over a pulley — i.e., tending to flex the knee — is just counteracted by
the postural action of the muscle. Now forcibly flex the knee nearly
to the full, bending it steadily and not too quickly, so that the move-
ment occupies a couple of seconds. Apart from a slight partial return
towards extension, and this not always, the limb remains in the new
position. Although the length of the vasto-crureus is now greater
than before, the weight needed to counterbalance its pull is practically
the same. That is to say, the muscle has assumed a new postural
length without any sensible change of tension. This is the so-called
' lengthening reaction ' of the posturally contracted muscle. The
' shortening reaction ' can be obtained by repeating the observations
in the reverse order — i.e., starting with the knee in nearly full flexion
(Sherrington) .
12. Reflexes in Man. — Study systematically on a fellow-student
and on yourself the chief reflexes described in the text (p. 914),
especially —
The Knee-jerk. — (i) Elicit the jerk in the usual way by striking the
ligamentum patellae and observe its height. Then cause the patient to
make a strong voluntary movement (squeezing the hands together or
clenching the jaws) at the moment when the tendon is struck, and note
whether the height is increased by ' reinforcement.'
(2) Attach a suitable recording apparatus to the foot of a person
sitting with his legs over the edge of a table, and record the jerks
elicited by taps made as uniform in strength as possible. A small
hammer worked by an electro-magnet or a spring might be employed
for this purpose. Compare the records obtained when the jerk is
elicited while the person is squeezing his hands together with those
previously obtained. The influence of mental activity, especially of ex-
citement or irritation (opportunities of studying such physical states
occasionally offer themselves in physiological laboratories) in increasing
the height of the knee-jerk may also be verified (Lombard).
13. Excision of Cerebral Hemispheres in the Frog (Fig. 402). —
Anaesthetize a frog lightly by putting it under a bell-jar or tumbler
PRACTICAL EXERCISES
with a small piece of cotton-wool soaked in ether. Put very little ether
on the cotton, and leave the frog only a very short time under the
bell-jar. Then, holding it in a cloth, make an
incision through the skin over the skull in the
mesial line. With scissors open the cranium
about the position of a line drawn at a tangent
to the posterior borders of the two tympanic
membranes. Remove the roof of the skull in
front of this line with forceps, scoop out the
cerebral hemispheres, and sew up the wound.
As soon as the animal has recovered from the
ether, the phenomena described at p. 947 should
be verified. The frog will swim when thrown
into water, will refuse to lie on its back, and
will not fall if the board on which it lies be
gradually slanted. Let the frog live for a
day, keeping it in a moist atmosphere ; then
expose the brain again, determine the reflex
time by Tiirck's method ; apply a crystal of
common salt to the optic lobes, and repeat the
observation. The reflex movements will be
completely inhibited or delayed. Remove the
salt, wash with physiological salt solution,
excise the optic lobes, and see whether the
frog will now swim.
14. Excision of the Cerebral Hemispheres in
a Pigeon. — Feed a pigeon for two or three days
on dry food, etherize it by holding a piece of
cotton- wool sprinkled with ether over its beak,
or inject into the rectum | gramme chloral
hydrate. The pigeon being wrapped up in a
cloth, and the head held steady by an assis-
tant, the feathers are clipped off the head, an
incision made in the middle line through the
skin, and the flaps reflected so as to expose
the skull. Cut through the bones with scissors,
and make a sufficiently large opening to bring the cerebral hemispheres
into view. They are now rapidly divided from the corpora bigemina
and lifted out with the handle of a scalpel. The bleeding is very free, but
may be partially controlled by stuffing the cavity with the vegetable
fibre known as Pengavar Djambi, which should be removed in a few
minutes, the wound cleansed with iodoform gauze wrung out of physio-,
logical salt solution at 50° C., and sewed up. Study the phenomena
described on p. 948.
15. Stimulation of the Motor Areas in the Dog. — (a) Study a hardened
brain of a dog, noting especially the crucial sulcus (Fig. 382, p. 950), the
convolutions in relation to it, and the areas mapped out around it by
Hitzig and Fritsch and others. (6) Inject morphine under the skin of
a dog. Set up an induction-coil arranged for tetanus, with a single
Daniell in the primary circuit. Connect a pair of fine but not sharp-
pointed electrodes through a short-circuiting key with the secondary.
Fasten the dog on the holder, belly down, and put a large pad under the
neck to support the head. Clip the hair over the scalp. Feel for the
condyles of the lower jaw, and join them by a string across the top of the
head. Connect the outer canthi of the eyes by another thread. The
crucial sulcus lies a little behind the mid-point between these two lines.
Now give the dog ether, make a mesial incision through the skin down
Fig. 402. — Brain of Frog
(after Steiner). a, cere-
bral hemispheres ; b,
position of optic thala-
mi; c, optic lobes; d,
cerebellum; e, medulla
oblongata ; A , upper
end of spinal cord.
1002
to the bone, and reflect the flaps on either side. Detach as much of the
temporal muscle from the bone as is necessary to get room for two
trephine holes, the internal borders of which must be not less than
J inch from the middle line, so as to avoid wounding the longitudinal
sinus. Carefully work the trephine through the skull, taking care not
to press heavily on it at the last. Raise up the two pieces of bone with
forceps, connect the holes with bone forceps, and enlarge the opening as
much as may be necessary to reach all the ' motor ' areas. At this
stage only enough ether should be given to prevent suffering. Now
unbind the hind- and fore-limbs on the side opposite to that on which
the brain has been exposed, apply blunt electrodes successively to the
areas for the fore- and hind-limbs, and stimulate.* The ' unipolar '
method of stimulation (p. 951) may also be employed. Contraction of
the corresponding groups of muscles will be seen if the narcosis is not
too deep. Movements of the head, neck, and eyelids may also be called
forth by stimulating the ' motor ' areas for these regions. Stimulation
in front of the crucial sulcus may also cause great dilatation of the pupil,
the iris almost disappearing. The dilatation takes place most promptly
and is greatest on the opposite side, but the pupil on the same side is
also widened. Even after section of both vago-sympathetic nerves in
the neck, a slow and slight dilatation, greatest perhaps on the same side,
may be caused by cortical stimulation. Repeat the whole experiment
on the opposite side of the brain. In the course of his observations the
student will perhaps have the opportunity of seeing general epileptiform
convulsions set up by a localized excitation. They begin in the group
of muscles represented in the portion of the cortex directly stimulated.
After the convulsions have been sufficiently studied, they should be
again induced, and the stimulated ' motor ' area rapidly excised during
their course. In some cases this will be followed by immediate cessation
of the spasms, (c) The same animal can be used for stimulation of the
spinal nerve-roots, as described in Experiment I (p. 995).
• It is not necessary to remove the dura mater.
CHAPTER XVII
THE AUTONOMIC NERVOUS SYSTEM (THE SYMPATHETIC
AND ALLIED NERVES)
THE efferent fibres of the body can be divided into two classes:
(i) Those which supply multinuclear striated muscle (skeletal
muscle) ; (2) those which supply other structures (smooth muscle,
heart muscle, glands). The second group is called ' autonomic,'
to indicate that it possesses a certain independence of the central
nervous system, although this independence is far from absolute.
The autonomic fibres arise from four regions of the central nervous
system : (i) The mid-brain; (2) the bulb; (3) the thoracic and upper
lumbar cord; (4) the sacral portion of the cord. All autonomic
fibres after issuing from the central nervous system end sooner or
later by forming synapses around nerve-cells of sympathetic type,
by whose axons the path is continued to the peripheral distribution.
The autonomic path accordingly comprises two neurons, the fibre
which arises from the brain or cord being termed the ' pregang-
lionic,' and that which arises from the sympathetic ganglion the
' postganglionic ' fibre.
The autonomic fibres originating in the mid-brain emerge in the
oculo-motor nerve, and form synapses with cells in the ciliary
ganglion, which in turn send fibres to the ciliary muscle and the
constrictor muscle of the iris (pp. 923, 1024), The bulbar autonomic
fibres emerge in the seventh, ninth, and tenth cranial nerves. Those
in the vagus include inhibitory fibres for the heart muscle, motor and
inhibitory fibres for the smooth muscle of the alimentary canal from
the oesophagus to the descending colon, and for the muscles of the
trachea and lungs, and secretory fibres for the gastric glands and
the pancreas. The sympathetic ganglion cells with which these
preganglionic fibres form synapses have not always been definitely
located, but lie near or in the tissue supplied (p. 181). The auto-
nomic fibres in the seventh and ninth nerves supply the mucous
membranes of the mouth and nose with vaso-dilator and secretory
fibres. The preganglionic portion of the path terminates in such
ganglia as the submaxillary and sublingual (p. 391) and the spheno-
palatine and otic ganglia.
1003
1004
THE AUTONOMIC NERVOUS SYSTEM
Mid-
\Bulb
1
The part of the autonomic system which originates in the middle
region of the spinal cord (in the cat from the first thoracic to the
fourth or fifth lumbar nerves) is the sympathetic proper. The
course of the fibres has already been described in connection with
the vaso-motor nerves (p. 181)- Among the fibres may be men-
tioned the dilators of the pupil, the augment ors
of the heart, motor (viscero-motor) and inhibi-
tory fibres for the smooth muscle of the alimen-
tary canal, sweat-secretory, pilo-motor and vaso-
constrictor fibres. The preganglionic fibres issue
from the cord in the anterior roots, and leave
the corresponding spinal nerve in the white
ramus communicans, which connects it with the
corresponding ganglion of the lateral sympa-
thetic chain. A fibre may either end in this
ganglion by forming a synapse, or it may run up
or down in the chain for some distance before
terminating. Some of the preganglionic fibres,
particularly the vaso-constrictors for the ab-
dominal and pelvic viscera, do not end in the
lateral chain at all, but, issuing from it still as
medullated fibres, terminate in one of the pre-
vertebral ganglia — e.g., coeliac ganglion, inferior
mesenteric ganglion — from which postganglionic
fibres proceed to the viscera, as previously
described (p. 332). The postganglionic fibres
arising from cells of the lateral ganglia return
as non-medullated fibres in grey rami com-
municating to the spinal nerves, and are dis-
tributed with them to the head, limbs, and the
superficial parts of the trunk.
The autonomic fibres arising from the sacral
region of the cord emerge as preganglionic fibres
in the anterior roots of the second to the fourth
sacral nerves, from which they pass to the pelvic
nerve (nervus erigens) (pp. 181, 332). They
comprise vaso-dilator fibres for the rectum, anus,
and external genitals, motor (viscero-motor)
fibres for the smooth muscle of the descending
colon, rectum, and anus, inhibitory fibres for
the smooth muscle of the anus, and the
muscles of the external genitals, motor fibres for the bladder, etc.
The preganglionic fibres terminate by forming synapses with
sympathetic ganglion cells in the pelvic plexus, or in the neighbour-
hood of the organs which they supply. From these ganglion cells
the postganglionic fibres arise.
I
Fig. 403. — Diagram
showing the Cen-
tral Origin of the
Autonomic Fibres
(Langley).
FUNCTIONS OF THE AUTONOMIC SYSTEM 1003
Action of Nicotin and Adrenalin on the Autonomic System. —
The action of nicotin upon the sympathetic ganglion cells, or the
link between them and the preganglionic fibres, which has been
taken advantage of in tracing the course of the autonomic fibres,
has already been described (p. 182). The special relation of adrena-
lin or epinephrin to the sympathetic, although not to the rest of the
autonomic system, has also been alluded to (p. 655).
Functions of the Autonomic System. — The functions of the auto-
nomic nerves are sufficiently defined by the enumeration of the
peripheral organs with which they are connected. It is obvious
that they preside over functions for the most part withdrawn from
the control of the will, the so-called vegetative functions, like the
heart-beat, the tone of the bloodvessels, the movements of the
alimentary canal and of the uterus, the erection of the hairs, and
the secretion of sweat. It is no doubt advantageous that these
functions should be withdrawn from voluntary control, and this
withdrawal is, we may assume, secured either by the absence of
anatomical connections between the regions of the cortex connected
with voluntary movements and the ganglion cells in the cerebro-
spinal axis from which the preganglionic fibres arise, or by the
existence of a high threshold of resistance in such paths as exist.
There is no anatomical or physiological reason why autonomic
fibres should not carry impulses which would elicit voluntary move-
ments were such impulses once shunted on to an autonomic path,
and certain autonomic fibres do innervate structures which are
under voluntary control — e.g., the fibres to the ciliary muscle of
the eye and those to the urinary bladder. The power of voluntarily
accelerating the heart possessed by some individuals (p. 172) is
a further instance showing that the general rule is broken by ex-
ceptions.
CHAPTER XVIII
THE SENSES
HITHERTO we have been considering from a purely objective standpoint
the organs that compose the body, and their work. The student has
been assumed to be in the little world — the ' microcosm ' — of organiza-
tion which he has been studying, but not of it. He has listened to the
sounds of the heart, seen its contraction, felt it hardening under his
fingers; but we have not inquired as to the meaning or the mechanism
of this hearing, seeing, and feeling. We have now to recognize that all
our knowledge of external things comes to us by the channels of the
senses, and, like the light that falls through coloured windows on the floor
of a church, is tinged, and perhaps distorted, in the act of reaching us.
The Senses in General. — The old and orthodox enumeration of
' the five senses ' of sight, hearing, touch, taste, and smell, must
be augmented by at least two more, the senses of pressure and
temperature. The so-called temperature sensations are themselves
divisible into two groups of quite distinctive quality, sensations of
warmth and sensations of cold. The power of appreciating the
amount of a muscular effort; the power of localizing the various
portions of the body in space ; the sensations of pain, tickling, itching,
hunger, and thirst; the sensations accompanying the generative
act, etc., can certainly be no longer lumped together in the omnium
gatherum of 'common sensibility.' They are more appropriately
regarded as separate senses subserved by special nerves, and
perhaps connected with definite centres. In the development of
a simple sensation we may distinguish three stages: the stimulation
of a peripheral end-organ, the propagation of the impulses thus set
up along an afferent nerve, and their reception and elaboration in
a central organ.
We do not know in what manner a series of transverse vibrations in
the ether when it falls upon the eye, or a series of longitudinal vibrations
in the air when it strikes the ear, excites a sensation of light or sound.
We can trace the ray of light through the refractive media of the eyeball,
see it focussed on the retina, lead off the current of action set up in that
membrane, which, doubtless, gives token of the passage of nervous
impulses into and up the optic nerve. We can even follow the nervous
impulses to a definite portion of the cortex of the occipital lobe, and
determine that if this is removed no sensation of sight will result from
1006
THE SENSES IN GENERAL 1007
any excitation of retina or optic nerve. And it is fair to conclude that
in some manner this part of the cerebral cortex is essential to the pro-
duction of visual sensations. But in what way the chemical or physical
processes in the axis-cylinders or nerve-cells are related to the psychical
change, the interruption of the smooth and unregarded flow of conscious-
ness which we call a sensation of light, we do not know. To our
reasoning, and even to our imagination, there is a great gulf fixed between
the physical stimulus and its psychical consequence; they seem incom-
mensurable quantities; the transition from light to sensation of light is
certain, but unthinkable.
Each kind of peripheral end-organ is peculiarly suited to respond
to a certain kind of stimulus. The law of ' adequate ' or ' homol-
ogous ' stimuli is an expression of this fact. The ' adequate '
stimuli of the organs of special sense may be divided into (i) vibra-
tions set up at a distance without the actual contact of the object
— e.g., light, sound, radiant heat; (2) changes produced by the
contact of the object — e.g., in the production of sensations of taste,
touch, pressure, alteration of temperature (by conduction). Mid-
way between (i) and (2) lies the adequate stimulus of the olfactory
end-organs, which are excited by material particles given off from
the odoriferous body and borne by the air into the upper part of
the nostrils.
The end-organs of the special senses all agree in consisting essentially
of modified ectodermic cells, but they occupy areas by no means pro-
portioned to their importance and to the amount of information we
acquire through them. The extent of surface which can be affected by
light in a man is not more than 20 sq. cm. ; the endings of both nerves of
ligaring taken together do not at most expand to more than 5 sq. cm.;
the olfactory portion of the mucous membrane of the nose has an area of
not more than 10 sq. cm. ; the sensations of taste are ministered to by
an area of less than 50 sq. cm. ; the end-organs of the senses of pressure,
touch, and temperature are distributed over a surface reckoned by
square metres. As the physiological status of the sensory end-organs
rises, their anatomical distribution tends to shrink. The organs of com-
paratively coarse and common sensations are widely spread, inter-
mingled with each other, and seated in tissues whose primary function
may not be sensory at all. Even the nerve-endings of the sense of taste
are not confined to one definite and circumscribed patch, but scattered
over the tongue and palate ; and both tongue and palate are at least as
much concerned in mastication and deglutition as in taste. The
olfactory portion of the nasal mucous membrane, although a continuous
area with fairly distinct boundaries, is still a part of the general lining
of the nostril. The epithelial surfaces which minister to the supreme
sensations of sight and hearing — the retina and the sensitive structures
of the cochlea — are the most sequestered of all the sensory areas, as the
organs of which they form a part are, of all the organs of sense, the most
highly specialized in function, and anatomically the most limited. But
although hidden in protected hollows, they are endowed, either in virtue
of their own movements or of those of the head, with the power of
receiving impressions from every side, and their actual size is thus in-
definitely multiplied.
ioo8 THE SENSES
SECTION I. — VISION.
Physical Introduction. — Physically, a ray of light is a series of dis-
turbances or vibrations in the luminiferous ether, which radiates out
from a luminous body in what is practically a straight line. The ether
is supposed to fill all space, including the interstices between the mole-
cules of matter and the atoms of which those molecules are composed.
Suppose a bar of iron to be gradually heated in a dark room. In the
cold iron the molecules are moving on the average at a relatively slow
rate, and the waves set up in the ether by their vibrations are compara-
tively long. Now, the. long ethereal vibrations do not excite the retina,
because it is only fitted to respond to the impact of the shorter waves ;
and, indeed, the long waves are largely absorbed by the watery media
of the eye. As the temperature of the iron bar is increased, the mole-
cules begin to move more quickly, and waves of smaller and smaller
length, of greater and greater frequency, are set up, until at last some
of them are just able to stimulate the retina, and the iron begins to glow
a dull red. As the heating goes on the molecules move more quickly
still, and, in addition to waves which cause the sensation of red, shorter
waves that give the sensation of yellow appear. Finally, when a high
temperature has been reached, the very shortest vibrations which can
affect the eye at all mingle with the medium
and long waves, and the sensation is one of
intense white light.
We have said that a ray of light travels
in a straight line, and the direction of the
straight line does not change as long as the
medium is homogeneous. But when a ray
reaches the boundary of the medium through
which it is passing, a part of it is in general
turned back or reflected. If the second
medium is transparent (water or glass, e.g.),
the greater part of the ray passes on through
it, a smaller portion is reflected. If the
Fig. 404. — Reflection from a second medium is opaque, the ray does not
Plane Mirror. penetrate it for any great distance; if it is
a piece of polished metal, e.g., nearly the
whole of the light is reflected ; if it is a layer of lampblack, very little
of the light is reflected, most of it is absorbed.
Reflection. — The first law of reflection is that the reflected ray, the ray
which falls upon the reflecting surface (incident ray), and the normal to the
surface, are in one plane. The second law is that the reflected ray makes
with the perpendicular (normal) to the reflecting surface the same angle
as the incident ray. A corollary to this is that a ray perpendicular to
the surface is reflected along its own path.
Reflection from a Plane Mirror. — Let a ray of light coming from the
point P (Fig. 404) meet the surface DE at B, making an angle PBA with
the normal to the surface. The reflected ray BC will make an equal
angle ABC with the normal; and the eye at C will see the image of P
as if it were placed at P', the point where the prolongation of BC cuts
the straight line drawn from P perpendicular to DE. This is the posi-
tion of an ordinary looking-glass image.
Reflection from a Concave Spherical Mirror. — A spherical surface may
be supposed to be made up of an infinite number of infinitely small plane
surfaces. The normal to each of these plane surfaces is the radius of
the sphere, and the reflected ray makes with the radius at the point of
VISION
1009
incidence the same angle as the incident ray. Let D (Fig. 405) be the
middle point of the mirror, and C its centre of curvature — i.e., the
centre of the sphere of which it is a segment. Then CD is the principal
axis, and any other line through C which cuts the mirror is a secondary
axis. When the mirror is a small portion of a sphere, rays parallel to
the principal axis are focussed at the principal focus F midway between
C and D; rays parallel to any secondary axis are focussed in a point
••^i^^"""^"«^^^^^^" --^^^^^^^^—
Fig. 405. — Reflection irom a , Concave Fi^. 406. — Formation of Real Inverted
Spherical Mirror. Image by a Concave Spherical Mirror,
lying on that axis ; and rays diverging from a point on any axis are
focussed in a point on the same axis.
These facts afford a simple construction for finding the position of
the image of an object formed by a concave mirror. Let AB be the
object (Fig. 406). Then the image of A is the point in which all rays
proceeding from A and falling on the mirror, including rays parallel to
the principal axis, are focussed. But the ray AE, parallel to the prin-
cipal axis, passes after reflection through the principal focus F, there-
fore the image of A must lie on the straight line EF. .If any secondary
axis ACD be drawn, the
image of A must lie on
ACD. It must therefore
be the point of intersec-
tion, a, of EF and ACD.
Similarly, the image of B
must be the point of inter-
section, b, of GF and BCH.
The image ab of an object
AB farther from the mirror
than the principal focus
is real and inverted. The
Purkinje-Sanson image re-
flected from the concave
anterior surface of the
vitreous humour (Fig. 421)
is an example.
After reflection from a convex mirror, rays of light always diverge, and
only erect, virtual images are formed — i.e., images which do not really
exist in space, but which, from the direction of the rays of light, we, judge
to exist. The position of the image of an object AB (Fig. 407) may be
found by a construction similar to that for reflection from a concave
mirror. The image of a flame reflected from the anterior surf ace of the
cornea or lens is erect and virtual. It diminishes in size with increase
in the curvature or convexity of the reflecting surface (Fig. 421).
Refraction. — A ray of light passing from one medium into another
has its velocity, and consequently its direction, altered. It is said to
64
Fig. 407. — Formation of Image by a Convex
Mirror.
toio
be refracted. The first law of refraction is that the refracted ray is in
the same plane as the incident ray and the normal to the surface. The
second law is that the sine of the angle of incidence has a constant ratio
(for any given pair of media) to the sine of the angle of refraction. The
angle of incidence is the angle which the ray makes with the normal
to the surface, separating the two media ; the angle of refraction is the
angle made with the normal in the second medium. This ratio is called
the index of refraction between the two media. For purposes of com-
parison, the refractive index of a substance is usually taken as the ratio
of the sine of the angle of incidence to the sine of the angle of refraction
of a ray passing from air into the substance.
When a ray strikes a surface at right angles, it passes through without
suffering refraction. When a ray passes from a less dense to a denser
medium (e.g., from air to water), it is bent towards the perpendicular.
Fig. 40?. — Refraction at a Plane Surface,
AB is the incident; BD, the refracted
ray; CB, the normal to the surface.
When the ray passes from air into
another medium, the refractive index of
the latter is the fraction - — — .
Bin/5
Fig. 409. — Refraction by a Medium
bounded by Parallel Planes, P and
P'. The ray ABDE issues parallel
to its original direction; CB, FD,
normals to P and P'; o, angle of
incidence; 8, y, angles of refraction.
When it passes from a more dense to a less dense medium (as from
water to air), it is bent away from the perpendicular.
When a ray passes across a medium bounded by parallel planes, it
issues parallel to itself; in other words, it undergoes no refraction
(Fig. 409).
Refraction and Dispersion by a Prism. — The beam of light is bent
towards the .normal N as it passes across BA and away from the normal
N' as it passes across BC (Fig. 410) ; at both surfaces it is bent towards
the base of the prism AC. At the same time the light suffers dispersion
— that is, the rays of shorter wave-length are more refracted than those
of greater wave-length. The deviation of any given ray is measured by
the angle which the refracted ray makes with its original direction.
The amount of dispersion produced by a prism is measured by the
difference in the deviation of the extreme rays of the spectrum. The
dispersion produced by a given substance is proportional to the differ-
ence of its refractive indices for the extreme rays.
Refraction by a Biconvex Lens. — A straight line ABC passing through
the centres of curvature of the two surfaces of the lens is called the
principal axis. A point C lying on the principal axis between the
VISION
ton
two centres of curvature, and possessing the property that rays passing
through it do not surfer refraction, is called the optical centre of the
lens. Any straight line, DCE, passing through the optical centre, is a
secondary axis. Rays of light proceeding from a point in the principal
axis are focussed in a point on that axis. When the rays proceed from
an infinitely distant point in the principal axis — i.e., when they are
parallel to it — they are focussed in F, the principal focus. Similarly
rays parallel to, or
proceeding from, a
point- in a secondary
axis are focussed in
a point on that axis ;
but if the focus is to
be sharp, the angle
between the secon-
dary and the princi-
pal axis must not be
so large as is indi-
cated in Fig. 411.
Formation of Im-
age by Biconvex Lens
(Fig. 412).— Let AB
be the object; then
if AHD be the path
of a ray from A parallel to the principal axis, the image of A will be the
intersection of the straight line DF and the secondary axis passing
through A. Similarly, the image of B will be the intersection of GF
and the secondary axis BC. Where AB is farther from the lens than
the principal focus, the image ab is real and inverted. This is the case
with the image of an external object formed on the retina. When the
object is nearer than the principal focus, the image is virtual and direct.
Fig. 410. —Refraction and Dispersion by a Prism.
Fig. 411. — Refraction by a
Biconvex Lens.
Fig. 412. — Formation of Image by
Biconvex Lens.
The image formed by the objective of a microscope when the object is in
focus is real and inverted ; the ocular forms a virtual erect image of this
real image.
Refraction by a Biconcave Lens (Fig. 413). — Parallel rays are rendered
divergent by the lens; there is no real focus; but if the rays are pro-
longed backwards they meet in the virtual focus F, from which they
appear to come when received by the eye chrough the lens.
Formation of Image by Biconcave Lens (Fig. 414). — Let AB be the
object. Let AHDI be the path of a ray from any point A of the object
1012
THE SENSES
parallel to the principal axis. Produce DI backwards (dotted line);
it will pass through the principal focus F. Through A draw the second-
ary axis AC. The image of A must lie both on AC and on IDF i.e.,
it must be the intersection, a. of these straight lines. Similarly the
image of B is b, the intersection of KGF and BC. The image is virtual
and erect.
Absorption. — No substance is perfectly transparent; in addition to
what is reflected, some light is always absorbed. In other words, in
Fig. 413. — Refraction by
a Biconcave Lens.
Fig. 414. — Formation of Image by Biconcave Lens.
passing through a body some of the light is transformed into heat, a
portion of the energy of the short, luminous waves going to increase the
vibrations of the molecules of the medium, just as a wave passing under
a row of barges or fishing-boats set them swinging and pitching, and so
imparts to them a certain amount of energy, which is ultimately changed
into heat by friction against the water, and against each other, and bv
the straining and rubbing of
the chains at their points of
attachment. Some bodies ab-
sorb all the rays in the pro-
portion in which they occur in
white light ; whether looked at
or looked through, they appear
colourless or white. Other
substances absorb certain rays
by preference, and the amount
of absorption is proportional
to the thickness of the layer.
The colours of most natural
bodies are due to this selective
absorption. Even when looked
at in reflected light, they are
seen by rays that have pene-
trated a certain way into the
substance and have then been
Fig. 4I5. — Diagram to show Connection of Body reflected ; and, of course, a
Colour with Selective Atisorption. smaller number of the rays
which the body specially ab-
sorbs are reflected than of the rays which it readily transmits, for more
of the latter than of the former reach any given depth. This is called
' body colour '; and such substances have the same colour when seen by
reflected and by transmitted light. The colour of haemoglobin is due
to the absorption of the violet and many of the yellow and green rays,
as is shown by the position of the absorption bands in its spectrum (p. 51 ).
In Fig. 4 1 5 the violet rays are represented as being totally absorbed before
passing through the substance. Some of the green rays are reflected, some
VISION
1013
transmitted, some absorbed. The red rays are supposed to be mostly
reflected and transmitted, only to a slight extent absorbed. The colour
of such a substance, both when looked at and when looked through,
would therefore be that due to a mixture of red light with a smaller
quantity of green. Then there is another class of substances which owe
their colour to selective reflection. Certain rays only are reflected from
their surface, and the light transmitted through a thin layer is com-
plementary to the reflected light — that is, the reflected and transmitted
rays together would make up white light. These bodies have what is
called ' surface colour,' and include metals, various aniline dyes, and
other substances.
Comparative. — Many invertebrate animals possess rudimentary sense-
organs, by means of which they may receive certain luminous impres-
sions. It is true that the mere sensation of light is not in itself sufficient
for the exact appreciation of the form and situation of surrounding objects.
But even the closure of the eyelids does not prevent a person of normal
eyesight from distinguishing differences in the intensity of illumination.
Iris
TZars.
Cornea
^..Jdtliary tfuscle
•Suspensory
Ligament
-Sclerotic
Optic Nerve
—-. _,".»» 1 • •VWWXWUTOIU /
Fbvea Centnalis
Fig. 416. — Diagrammatic Horizontal Section of the Left Eye.
And it is possible that many of the humbler animals may, through the
pigment spots which are often called eyes, or perhaps, as in the earth-
worm, by means of end -organs more generally diffused in the skin,
attain to some such dim consciousness of light and shadow as will enable
them to avoid an obstacle or an enemy, to seek the sunny side of a
boulder or the obscurity of an overhangmg ledge of rock. But the
indispensable condition of distinct vision is that an image of each part
of an object should be formed upon a separate portion of the receiving
or sensitive surface. This condition is, to a certain exentt, fulfilled by
the compound eyes of some of the higher invertebrates (insects, e.g.).
Here rays from one point of the object pass through one of the funnel-
shaped elements of the compound eye, and rays from another point
1014
THE SENSES
Rod*
Cones.
through another. Rays striking obliquely on the facets are stopped
by the opaque partitions between them. In the Cephalopods we find
that this compound type of eye has already been abandoned ; the single
system of curved refracting surfaces so characteristic of the vertebrate
eye has made its appearance; and the formation of a clean-cut image
of the object on the retina, with the excitation of a sharply-bounded area
of that membrane, follows as a geometrical consequence from the theory
of lenses.
We have to consider (i) the mechanism by which an image is
formed on the retina, and (2) the events that follow the formation
of such an image and their relations to the stimulus that calls them
forth.
Structure of the Eye. — The eye may be described with sufficient
accuracy as a spherical shell, transparent in front, but opaque over
the posterior five-sixths of its
surface, and filled up with a
series of transparent liquids
and solids. The shell consists
of three layers concentrically
arranged, like the coats of an
onion: (i) An external tough,
fibrous coat, the sclerotic, the
anterior portion of which
appears as the white of the eye.
In front this external layer is
completed by the transparent
cornea, (2) A vascular layer,
the choroid, which, in the re-
stricted sense of the term, ends
in front in a series of folds or
plaits, the ciliary processes. The
choroid contains a greater or
smaller quantity of the black
pigment melanin. The ciliary
processes abut on the outer
boundary of the iris, which
may be looked upon as an
anterior continuation of the
choroidal or middle coat of the
eyeball. Between the corneo-
sclerotic junction and the an-
terior portion of the choroid is
interposed a ring of unstriped
muscular fibres, the ciliary
muscle. (3) The inner or sen-
sitive coat, termed the retina
(Fig. 417). This covers the
choroid as a delicate mem-
ciliary processes, where it ends in a
The optic nerve forms a kind of
Its point of entrance at
Fig. 417. — Diagram of Structure of Retina
(after Cajal). H, layer of nerve-fibres; G,
layer of ganglion cells; jF, internal mole-
cular layer ; E, internal nuclear layer ;
C, external molecular layer; B, external
nuclear layer; external limiting membrane ;
A , layer of rods and cones.
brane, extending to the
toothed margin, the ora serrata.
stalk to which the eyeball is attached.
the optic disc is a little nearer the median line than the antero-posterior
axis, which nearly passes through the centre of a small depression,
the fovea centralis, situated in the middle of the macula lutea, or
yellow spot. From the optic disc (^sometimes called the optic
VISION
1015
papilla) the optic nerve spreads over the retina as a layer of non-
medullated fibres, separated from the interior of the eyeball only
by the internal limiting membrane. This so-called membrane is formed
by the expanded feet of the fibres of Muller, which run like a scaffolding
or framework through nearly the whole thickness of the retina, ter-
minating at the outer limiting membrane. External to the layer of
nerve-fibres is the stratum of large ganglion cells, whose axons they
are; next to this the inner molecular layer, or inner synapse layer,
made up largely of the branching dendrires of these cells. The fifth
layer is the inner granular or nuclear layer, containing many fusiform
(bipolar) ' granule ' cells which send out axons into the fourth, and
dendrites into the sixth, or outer molecular layer, and are thus con-
nected with the ganglion cells of the third layer on the one hand, and
with the terminations of the rod and cone fibres of the seventh or outer
nuclear layer on the other. The arborizations of the axons of these
bipolar cells are situate at different
levels in the internal molecular
layer. The bipolar cells connected
with the rod fibres send their axons
right through the internal, mole-
cular layer to arborize around the
bodies of the ganglion cells, whereas
the axons of the bipolar cells con-
nected with the cone fibres ramify
about the middle of the layer
(Fig. 417). The seventh stratum
receives its name from the large
number of nuclei which it contains.
These belong to structures con-
tinuous with the rods and cones
of the ninth layer, which is divided
from the seventh by the external
limiting membrane. Each rod is
prolonged into the external nuclear
layer as a fine fibre, which has on
its course a swelling containing a
nucleus, and terminates (in mam-
mals) in a fine knob in the external
molecular layer among the den-
drites of the bipolar cells. Each
cone of the rod and cone layer is
directly prolonged into a nucleated enlargement in the external nuclear
layer. From this enlargement a fibre (cone fibre) , of considerably greater
calibre (hi mammals) than the rod fibre, passes into the external mole-
cular layer, where it forms an arborization, which comes into relation
with the arborization of the dendrites of a bipolar cells. At the fovea
centralis the rods are entirely absent, and the other layers of the retina
greatly thinned; over the optic disc neither rods nor cones are present.
The disc is pierced by the retinal bloodvessels (Fig. 418').
External to the rods and cones is a sheet of pigmented epithelial cells
of hexagonal shape, belonging to the choroid, but remaining attached
to the retina when the latter is separated, and therefore often reckoned
as its most external layer.
A little behind the cornea and anterior to the retina is the lens, en-
closed in a capsule, and attached to the choroid by the suspensory
ligament, or zonule of Zinn. The iris hangs down in front of the lens
like a diaphragm, with a central hole, the pupil. Incorporated in the
Fig. 418.— Retinal Bloodvessels (Henle).
The arteria centralis is seen issuing
from the optic dies and branching over
the retina. The shaded area in the
middle of the figure represents the
yellow spot with the fovea centralis in
its centre.
i oi6 THE SENSES
stroma or framework of the iris are two arrangements of smooth mus-
cular fibres, which confer on it the power of adjusting the size of the
pupil. One of these — the sphincter pupillae — consists of a well-defined
band of concentric fibres surrounding the margin of the pupil. The
other — the dilator pupillae — is less sharply differentiated. It is repre-
sented by radial bundles of elongated, spindle-shaped cells running in
from the ciliary border of the iris towards the pupil. Between the iris
and the posterior surface of the cornea is the anterior chamber of the
eye, filled with the aqueous humour. Between the iris and the anterior
surface of the lens lies the posterior chamber, which is rather a potenial
than an actual cavity. The space between the lens and the retina is
accurately occupied by an almost structureless semi-fluid mass, the
vitreous humour, enclosed by the delicate hyaloid membrane, which in
front is reflected over the folds of the ciliary processes, and blends with
the suspensory ligament of the lens. The attachment of the suspensory
ligament is rendered firmer by the connection of this part of the hyaloid
membrane to a circular fibrous portion of the vitreous. Around the
edge of the lens is left a space, the canal of Petit.
Chemistry of the Refractive Media. — The aqueous humour is a per-
fectly colourless, watery liquid, of slightly alkaline reaction to litmus.
The specific gravity is about 1008, and the total solids about i per
cent. Of the solids the inorganic salts (mainly sodium chloride) con-
stitute much the largest portion. A very small amount of protein
(o-oi to 0-04 per cent.) is present, also a little dextrose (0-05 per cent.),
and minute traces of urea and other substances. The liquid of the
vitreous humour has a very similar composition, except that it contains
a mucin-like body, hyalomucoid, to the amount of 0-06 to o-i per cent.
A similar mucin-like substance is present in the cornea. The freezing-
point of both liquids is a little lower than that of blood-serum, A being
ibout 0-6°.
The lens is far richer in solids than the aqueous and vitreous humours
with which it is in contact (30 to 35 per cent of solids, 60 to 65 per cent,
of water). The salts, with small quantities of lecithin and cholesterin,
make up about i per cent. ; the balance of the solids consists of proteins.
The physical alterations, with production of turbidity, which occur in
the lens, and presumably in its proteins, when water enters or leaves
it in too great amount through imbibition or osmosis, are of importance
in connection with the etiology of cataract. The anatomical and
physiological integrity of its capsule is a prime factor in the maintenance
of that high degree of transparency which is necessary for the function
of the lens. Cataract can be experimentally induced by injuring the
capsule. In like manner the cornea is protected against injurious
changes in its water-content (normally about 80 per cent.) and conse-
quent turbidity by the epithelium, which separates it from the tears,
and the endothelium, which separates it from the aqueous humour.
Secretion of the Intra-ocular Liquids. — The aqueous humour is
secreted by the uveal epithelium covering the ciliary processes, and
to some extent by that covering the iris. As it is continually secreted,
so it is continually absorbed, the absorbed constituents finding their
way eventually into the vein or venous sinus called the canal of Schlemm
and the bloodvessels of the iris and ciliary processes. The source of
the liquid of the vitreous body is also the uvea. While the intra-ocular
liquids differ from ordinary lymph, there is no reason to doubt that they
are secretions which contribute to the nutrition of those transparent
structures of the eye which are not, and, on account of their function,
cannot be supplied with bloodvessels. Their most obvious use is tc
VISION 1017
maintain the proper intra-ocular pressure on which the geometrical
figure of the eyeball, and therefore its efficiency as an optical instrument,
depend. The balance between secretion and absorption is accurately
adjusted in health, but in disease it may be upset, as in glaucoma, where
the intra-ocular tension is so much increased as to interfere with the
circulation, and injuriously affect the nutrition and function of the retina.
Experimentally, occlusion of all the arteries supplying the head causes
a rapid fall of tension, and the cornea becomes wrinkled and slack to
the touch. On restoring the circulation after not too long an interval,
the tension gradually returns to normal, and then becomes markedly
hypernormal, even when the general arterial pressure is still low. This
is probably due to the crippling of the elements which secrete and
absorb the intra-ocular fluids, or of the capillary walls, so that a proper
adjustment can no longer be attained, as happens in a tissue rendered
oedematous by temporary anaemia. Where asphyxia of the eyeball is
avoided or is brief the intra-ocular pressure varies directly as the blood-
pressure in the ocular vessels within a wide range (Henderson and Starling) .
Refraction in the Eye — Formation of the Retinal Image. — -The
amount of refraction which a ray of light undergoes at a curved
surface depends upon two factors — the radius of curvature of the
surface, and the difference between the refractive indices of the
media from which the ray comes and into which it passes. The
smaller the radius of curvature, and the greater the difference ol
refractive index, the more is the ray bent from its original direction.
A ray of light passing into the eye meets first the approximately
spherical anterior surface of the cornea, covered with a thin layer
of tears. Since the refractive index of the tears is much greater
than that of air, the ray is strongly refracted here. The anterior
and posterior surfaces of the cornea being practically parallel, and
the refractive indices of the tears and aqueous humour being nearly
equal, but little refraction takes place in the cornea itself. At the
anterior and posterior surfaces of the lens the ray is again refracted,
since the refractive index of the aqueous and vitreous humours is
less than that of the lens. The following tables show the radii of
curvature of the refracting surfaces and the refractive indices of
the dioptric media, as well as some other data which are of use in
studying the problems of refraction in the eye :
In accommodation for
Far Vision. Near Vision.
fCornea - - - - 7-8 mm. 7-8 mm.
Radius of curvature of -I Anterior surface of Ions - 10-0 ,, 6-0 ,,
[Posterior surface of lens - 6-0 ,, 5 -5 ,,
Anterior surface of cornea and an-
terior surface of lens - 3-6 ,, 3-2 ,,
Distance
between
Anterior surface of cornea and pos-
terior surface of lens - - 7*6 ,, 7-6
Anterior and posterior surface of lens - 4-0 ,, 4-4
Posterior surface of lens and retina - 14-6 ,, 14-6
Antero-posterior diameter of eye along the axis - 22-2 ,, 22-2
roiS
THE SENSES
Refractive Indices —
Air
Cornea - - - -
Aqueous humour •
Vitreous humour -
Lens (total refractive index) -
Water -.
I-OOO
1-377
1-3365
1-3365
1-437
1-335
It will be seen that the refractive indices of the aqueous and vitreous
humours are nearly the same as that of water. That of the lens
differs for its various layers, the central core having a higher re-
fractive index (1-411) than the more superficial portions (1-388).
Although such calculations are open to error, it has been computed
that the lens acts as a homogeneous lens of
the same curvatures, and with a refractive
index of 1-437 would do. This is called the
total refractive index of the lens.. The
apparent paradox that it is greater than the
refractive index even of the core is explained
by the consideration that the core taken by
itself has a greater curvature than the entire
lens, and therefore causes a greater amount of
refraction in proportion to its refractive index.
The optical problems connected with the
formation of the retinal image are complicated
by the existence in the eye of several media,
with different refractive indices, bounded by
surfaces of different and, in certain cases, of
variable curvature. For many purposes, how-
ever, the matter can be greatly simplified, and
a close enough approximation yet arrived at,
by considering a single homogeneous medium,
of definite refractive index, and bounded in
front by a spherical surface of definite curva-
ture, to replace the transparent solids and
liquids of the eye. The principal focus being supposed to lie
on the retina, the position of the nodal point — i.e., the point
through which rays pass without refraction — of such a ' reduced '
or ' schematic ' or ' simplified ' eye, and other constants, are shown
in the following table. The single refracting surface would be
situated behind the cornea and in front of the lens, at a rather
smaller distance from the anterior surface of the latter than from
the anterior surface of the former. The nodal point would be less
than half a millimetre in front of the posterior surface of the lens
(Fig. 419). The refractive index of the single transparent medium
would be a little greater than that of water.
Fig. 419. — The Reduced
Eye. S, the single
spherical refracting
surface, 2-2 mm. be-
hind the anterior sur-
face of the cornea; N,
the nodal point, 5 mm.
behind S ; F, the
principal focus (on the
retina), 20 mm. behind
S. The cornea and
lens are put in in
dotted lines in the
position which they
occupy in the normal
eye.
VISION 1019
Reduced Eye —
Radius of curvature of the single refracting surface - 5-1 mm.
Index of refraction of the single refracting medium - - 1*35* ,,
Antero-posterior diameter of redi.'^d eye (distance of
principal focus from the single refracting surface) - 20-0 ,,
Distance of the single refracting surface behind the
anterior surface of the cornea - - - - 2-2 ,,
Distance of the nodal point of the reduced eye from
[its anterior surface - - - - 5-0 ,,
Distance of the nodal point from the principal focus
(retina) - - ._..... i$.o it
Knowing the position of the centre of curvature of the single
ideal refracting surface — i.e., the nodal point of the reduced eye
— all that is necessary in order to determine the position of the
image of an object on the retina is to draw straight lines from its
circumference through the nodal point. Each of these lines cuts
the refracting surface at right angles, and therefore passes through
without any devi-
ation. The retinal
image is accord-
ingly inverted and
its size is propor-
tional to the solid
angle contained
between the lines
drawn from the p.g 420>_Figure to show how the Visuai Angle and
boundary OI the size of Retinal Image varies with the Distance of
object to the nodal an Object of Given Size. For the distant position
Doint Or the eaual of AB the visual angle is o, for the near position
, . T, (dotted lines) 8.
angle contained by
the prolongations of the same lines towards the retina. This angle
is called the visual angle, and evidently varies directly as the size
of the object, and inversely as its distance. Thus the visual angle
under which the moon is seen is much larger than that under which
we view any of the fixed stars, because the comparative nearness of
the earth's satellite more than makes up for its relatively small size.
The dimensions of the retinal image of an object are easily calculated
when the size of the object and its distance are known. For let AB
in Fig. 420 represent one diameter of an object, A'B' the image of this
diameter, and let AB7, BA', be straight lines passing through the nodal
point. Then AB and A'B' may be considered as parallel lines, and
the triangles of which they form the bases, and the nodal point the
common apex, as similar triangles. Accordingly, if D is the distance
of the nodal point from A, and d its distance from B', we have
-y=r— — T— • Now, d may approximately be taken as 15 mm. Suppose,
then, that the size of the moon's image on the retina is required. Here
0=238,000 miles, and AB (the diameter of the moon)= 2,160 miles.
* Or a little more than that of the aqueous humour.
1020 THE SENSES
•7 tfio A'T3' T sX'R'
Thus we get - —= ^-, or (say) —=--., from which A'B' (the
238,000 15 • }l no 15
diameter of the retinal image) = — — , or about \ mm.
no
A ship's mast 120 feet high, seen at a distance of 25 miles, will throw
,. , . ,, . 120 feet
on the retina an image whose height is -. — x 15 mm., i.e.,
25 miles J
i 20 feet i
— -f — T x 15 mm., or x 15 mm., equal to 0-013 mm., or
5,280x25 feet J 1,100 J
13 n in size. This is not much larger than a red blood-corpuscle, and
only four times the diameter of a cone in the fovea centralis, where the
cones are most slender. In this calculation the effect of aberration
(p. 1027) in enlarging the image has been neglected. This effect is, of
course, proportionately greater for small and distant than for large and
near objects; and it is doubtful whether the smallest possible image
can be confined to an area of the retina of the size of a single cone.
Accommodation. — A lens adjusted to focus upon a screen the
rays coming from a luminous point at a given distance will not be
in the proper position for focussing rays from a point which is
nearer or more remote. Now, it is evident that a normal eye
possesses a great range of vision. The image of a mountain at a
distance of 30 miles, and of a printed page at a distance of 30 cm.,
can be focussed with equal sharpness upon the retina. In an
opera-glass or a telescope accommodation is brought about by
altering the relative position of the lenses ; in a photographic camera
and in the eyes of fishes and cephalopods, by altering the distance
between lens and sensitive surface ; in the eye of man, by altering
the curvature, and therefore the refractive power of the lens. That
the cornea is not alone concerned in accommodation, as was at one
time widely held, is shown by the fact that under water the power
of accommodation is not wholly lost. Now, the refractive index
of the cornea being practically the same as that of water, no changes
of curvature in it could affect refraction under these circumstances.
That the sole effective change is in the lens can be most easily
and decisively shown by studying the behaviour of the mirror
images of a luminous object reflected from the bounding surfaces
of the various refractive media when the degree of accommodation
of the eye is altered. Three images are clearly recognized: the
brightest an erect virtual image, from the anterior (convex) surface
of the cornea; an erect virtual image, larger, but less bright, from
the anterior (convex) surface of the lens ; and a small inverted real
image from the (concave) posterior boundary of the lens (Purkinje-
Sanson images). The second image is intermediate in position
between the other two. It is possible with special care to make
out a fourth image; but since it is reflected from the posterior
surface of the cornea, at which only a slight change in the refractive
index occurs, it is less brilliant than the first three. When the eye
is accommodated for near vision, as in focussing the ivory point of
VISION
1021
the phakoscope (Practical Exercises), the corneal image is unchanged
in size, brightness, and position. The middle image diminishes
in size, comes forward, and moves nearer to the corneal image.
This shows that the curvature of the anterior surface of the lens
has been increased — that is to say, its radius of curvature diminished
— for the size of the image of an object reflected from a convex
mirror varies directly as the radius of curvature. A slight change
takes place in the image from the posterior surface of the lens,
indicating a small increase of its curvature too. By means of a
method founded on the observation of the changes in these images,
and a special instrument called an ophthalmometer which allows
of their measurement, Helmholtz
has calculated that during maxi-
mum accommodation, the radius
of curvature of the anterior surface
of the lens is only 6 mm., as com-
pared with 10 mm. when the eye
is directed to a distant object and
there is no accommodation. When
the lens has been removed for
cataract, fairly distinct vision may
still be obtained by compensating
for its loss by convex spectacles
of suitable refractive power (10
diopters* for distant vision, and
15 diopters for the distance at
which a book is usually held), but
no power of accommodation re-
mains. The person does indeed
contract the pupil in regarding a
near object, just as happens in the
intact eye; the most divergent
rays are thus cut off and the image
made somewhat sharper, and there
may appear to be some faculty of
accommodation left. But the loss
of the whole iris by operation does
not affect accommodation in the least; the iris, therefore, takes
no part in it. That no change in the antero-posterior diameter
of the eyeball, caused by its deformation by the contraction of the
^extrinsic muscles, can have any share in accommodation, as has
* A diopter (i D.) is the unit of refractive power generally adopted in
measuring the strength of lenses, and corresponds to a lens of i metre focal
length. A lens of 2 diopters (2 D.) has a focal length of £ metre, a lens of
4 diopters (4 D.) a focal length of J metre, and so on. The diverging power
of concave lenses is similarly expressed in diopters with the negative sign
prefixed. Thus, a concave lens of i metre focal length has a strength of — i D..
and will just neutralize a convex lens of i D.
Fig. 421. — Purkinje - Sanson Images.
A, in the absence of accommoda-
tion; B, during accommodation for
a near object. The upper pair of
circles enclose the images as seen
when the light falls on the eye.
through a double slit on a pair of
prisms; the lower pair show the
images seen when the slit is single
and triangular in shape.
1022 THE SENSES
been suggested, is clearly proved by the fact that atropine, which
does not affect the action of these muscles, paralyzes the mechanism
of accommodation. To the consideration of that mechanism we
now turn.
The Mechanism of Accommodation. — While everybody is agreed
that the main factor in accommodation is the alteration in the
curvature of the lens, there is by no means the same unanimity
as to the manner in which this is brought about. Helmholtz's
explanation, which has long been the most popular, is as follows:
In the unaccommodated eye the suspensory ligament and the
capsule of the lens are tense and taut, the anterior surface of the
lens is flattened by their pressure, and parallel rays (or, what is the
same thing, rays from a distant object) are focussed on the retina
without any sense of effort. In accommodation for a near object,
the meridional or antero-posterior fibres of the ciliary muscle by
their contraction pull forward the choroid and relax the suspensory
ligament. The elasticity of the lens at once causes it to bulge
forwards till it is again checked by the tension of the capsule.
The explanation of Helmholtz, although widely adopted in the text-
books, has not escaped question in the archives. Tscherning has put
forward the view that when the ciliary muscle contracts, the suspensory'
ligament is pulled backwards and outwards. Its tension is thus in-
creased, and the soft external layers of the lens are in consequence
moulded upon the harder nucleus, so as to increase the curvature
especially around the anterior pole. And Schoen, reviving a similar
theory originated fifty years ago by Mannhardt, believes that the
ciliary muscle, in contracting, exerts pressure on the anterior portion
of the lens, and so increases its curvature. He likens the process to the
bulging of an indiarubber ball when it is held in both hands and com-
pressed by the fingers a little behind one of the poles. It will be ob-
served that in both of these theories the suspensory ligament is supposed
to be stretched during accommodation, not relaxed as Helmholtz sup-
posed. While they have certain advantages over the theory of Helm-
holtz, particularly in taking account of the presence of radial and circular
as well as meridional fibres in the ciliary muscle, they do not agree so
well with such experimental tests as have been applied, and therefore
Helmholtz's explanation must still be regarded as the best.
It is supported by the observation .of Hess that when the ciliary
muscle has been very strongly contracted by eserine the lens can be
observed to move about with each slight movement of the eye. The
suspensory ligament must therefore be slackened by the contraction of
the ciliary muscle. (When atropine is applied the movability of the
lens soon disappears, owing to paralysis of the ciliary muscle. These
facts were first established in patients after iridectomy, but have also
been demonstrated in the normal eye. Even under the influence of
gravity alone, without any movements of the eye, the lens sinks about
± to J mm. in strong accommodation. An additional proof that the
suspensory ligament is perfectly slack during accommodation is derived
from the result of simultaneous measurements in animals of the pressure
in the anterior chamber and in the vitreous. Even in strong accommo-
dation no alteration occurs, although even slight contact with the outer
surface of the eyeball or contraction of the external eye muscles causes
VISION 1023
a distinct effect. In two cavities separated by a slack membrane no
differences of pressure would be expected.
Anderson Stuart lays stress upon the function of those fibres of the
suspensory ligament which are attached to the vitreous body, and are
put under tension by the contraction of the ciliary muscle, in anchoring
the lens during strong accommodation. He believes that the liquid
contents of the hyaloid canal move from its anterior to its posterior end
in accommodation, and in the opposite direction when accommodation
is relaxed, and that this movement tends to prevent strains in the
vitreous.
In cephalopods and fishes, which are normally short-sighted, accom-
modation for objects at a distance is effected by a movement of the lens
towards the retina. In the fish's eye this is accomplished by the con-
traction of a special muscle, the retractor lentis. In amphibia and most
snakes the -lens is moved towards the cornea and away from the retina
by changes of intra -ocular pressure (Beer).
Innervation of the Ciliary Muscle and the Muscles of the Iris. — The
ciliary muscle and the sphincter pupillae are supplied by autonomic
fibres (p. 1004) .reaching them through the short ciliary nerves arising
from the ciliary ganglion (Fig. 422). The preganglionic fibres take
origin from cells in the anterior part of the oculo-motor nucleus in the
mid -brain. Passing to the orbit in the third nerve, they reach the
ciliary ganglion, and end there by forming synapses with some of its
cells. The axons of these cells continue the path as post-ganglionic
fibres in the short ciliary nerves. The dilator pupilla? is supplied by the
long ciliary nerves coming from the ophthalmic branch of the fifth
nerve.
The preganglionic dilator fibres pass out by the anterior roots of the
first three thoracic nerves (dog, cat, rabbit), accompanied by vaso-
constrictor fibres for the iris. Reaching the sympathetic chain through
the corresponding rami communicantes, they traverse the first thoracic
ganglion, the annulus of Vieussens, the inferior cervical ganglion, and
the cervical sympathetic. They end by arborizing around some of the
cells of the superior cervical ganglion, whose axons eventually arrive at
the Gasserian ganglion, and running along the ophthalmic division of
the trigeminal to the eye, reach the iris by its long ciliary branches.
The exact origin of the dilator path in the brain has not been defi-
nitely settled. Some place it in the mid-brain, others in the bulb.
There must be at least one neuron on the path central to the spinal
neuron whose axon emerges from the cord as a preganglionic fibre.
The lower cervical and upper thoracic portion of the spinal cord has
received the name of the cilio-spinal region from its relation to the
pupillo-dilator fibres. It must not be looked upon as a centre in any
proper sense of the term, but rather as the pathway by which these
fibres pass down from the bulb, and where they may accordingly be
tapped by stimulation.
Stimulation of certain areas on the cortex of the frontal lobe of the
cerebrum (p. 1002) causes slight dilatation of the pupil even after the
sympathetic has been divided. This is due to inhibition of the pupillo-
constrictor fibres in the third nerve.
Changes in the Pupil during Accommodation. — It has been already
mentioned that along with the alteration in the curvature of the
lens a change in the diameter of the pupil takes place in accommo-
dation. When a distant object is looked at, the pupil becomes
larger ; when a near object is looked at, it becomes smaller. Narrow-
THE SENSES
ing of the pupil is thus associated with contraction of the ciliary
muscle, and widening of the pupil with its relaxation.
This physiological correlation has its anatomical counterpart ; for the
third nerve supplies both the iris and the ciliary muscle. Stimulation
of the nerve within the cranium causes contraction of the pupil, while
stimulation of certain portions of its nucleus in the floor of the third
ventricle and the Sylvian aqueduct or of the short ciliary nerves
(Fig. 422), which receive branches from the third nerve, or of the
ganglion itself, is followed by that change in the anterior surface of the
lens which constitutes accommodation (Hensen and Voelckers). This
can be observed either through a window in the sclerotic in a dog or by
following the movements of a needle thrust into the eyeball. By
carefully localized stimulation near the junction of the aqueduct with
in
Fig. 422. — Scheme of Innervation of Ciliary
and Iris Muscles (after Schultz). i, ciliary
ganglion; 2, oculo-motor nucleus; 3, spinal cell,
from which comes off the preganglionic fibre on
the pupillo-dilator path, which forms a synapse
with 4, a cell in the superior cervical ganglion.
The axon of 4 is shown passing (as an interrupted
line) through the Gasserian ganglion into the
ophthalmic division (Oph.) of the fifth nerve, V,
iid thence in a long ciliary nerve, 5, to the dilator of the iris, 8. From i axons
are shown passing by short ciliary nerves to the ciliary muscle, 6, and the constrictor
pupilleB, 7; 9, cell of origin (in mid-brain ?) of fibre which constitutes the central
neuron of the pupillo-dilator path; 10, optic nerve: III, third nerve; V, fifth nerve
with Gasserian ganglion.
the third ventricle, it is possible to bring about the forward bulging of
the lens without any change in the iris ; but the normal and voluntary
act of accommodation cannot be disjoined from the corresponding
alterations in the size of the pupil. Inward rotation of the eyes accom-
panies contraction of the pupil hi accommodation, and the question
may be raised whether the pupillary change is associated with the action
of the extrinsic muscles of the eyeball which cause convergence or with
the action of the intrinsic muscles which determine the changes in the
curvature of the lens. It is usually considered to be associated with
both. In any case, actual convergence is not necessary for the reaction,
since it may still be obtained on accommodation when convergence is
impossible on account of paralysis of the internal recti.
VISION 1025
Changes in the Pupil produced by Light. — It is not only by
accommodation that the size of the pupil may be affected. In
the dark it dilates, at first rapidly, then gradually, and it main-
tains the width it has reached for several hours. This has been
shown by taking photographs of the eye with the magnesium flash-
light. In this way the width of the pupil is recorded before it has
time to alter. Or a longer exposure to ultra-violet light, which
affects the pupil but little, may be employed. When ordinary
light falls upon the retina the pupil contracts, and the amount of
contraction is roughly proportional to the intensity of the light.
Contraction of the pupil to light is brought about by a reflex
mechanism, of which the optic nerve forms the afferent and the
oculo-motor the efferent path, while the centre is situated in the
floor of the aqueduct of Sylvius. The relation of this centre to
that which controls the changes in the pupil during accommodation
has not as yet been sufficiently elucidated; but this we do know,
that one of the paths may be interrupted by disease, while the other
is intact. For in tabes (locomotor ataxia), and in dementia para-
lytica (general paralysis), the light-reflex sometimes disappears,
while the constriction of the pupil in accommodation and conver-
gence still takes place (Argyll-Robertson pupil). Artificial stimula-
tion of the optic nerve has the same effect on the pupil as the
' adequate ' stimulus of light ; and in many animals (including man),
though not in those whose optic nerves completely decussate, there
is a consensual light-reflex — i.e., both pupils contract when one
retina or optic nerve is excited. This should be remembered in
using the pupil-reaction as a test of the condition of the retina.
For although the absence of contraction may show that the retina
of the eye on which the light is allowed to fall is insensible (unless
there is some physical hindrance to its passage, such as opacity
of the lens or cataract), the occurrence of contraction does not
exclude insensibility of the retina unless the other eye has been
protected from the light.
Stimulation of the cervical sympathetic causes marked dilata-
tion of the pupil, even when the third nerve is excited at the same
time. The pupillo-dilator fibres do not act by constricting the
bloodvessels of the iris. For dilatation of the pupil can be caused
in a bloodless animal by stimulating the sympathetic. And even
when the circulation is going on, a short stimulation of the sympa-
thetic causes dilatation of. the pupil without vaso-constriction,
while with longer excitation the dilatation of the pupil begins before
the narrowing of the bloodvessels. Nor does it seem possible to
accept the view that the sympathetic fibres are inhibitory for the
sphincter muscle of the iris. They act directly upon dilator muscu-
lar fibres. It has, indeed, long been known that in the iris of the
otter and of birds a radial dilator muscle exists; and it has been
65
1026 THE SENSES
shown by Langley and Anderson that in the ins of the rabbit, cat,
and dog, the presence of radially arranged contractile substance,
different it may be in some respects from ordinary smooth muscle,
must be assumed. Both the constrictor and the dilator muscles
of the iris are normally in a condition of greater or less tonic con-
traction, so that the size of the pupil at any given moment depends
on the play of two nicely balanced forces. Reflex dilatation of the
pupil through the sympathetic fibres is caused in man by painful
stimulation of the skin, by dyspnoea, by muscular exertion, and
in some individuals even by tickling of the palms. In animals the
stimulation of naked sensory nerves has the same effect. The ' start-
ing of the eyeballs from their sockets, ' which the records of torture so
often note, is due to a similar reflex excitation of the sympathetic
fibres supplying the smooth muscle of the orbits and eyelids.
Action of Drugs on the Function of the Intrinsic Eye Muscles. — The
local application of atropine causes temporary paralysis of accommoda-
tion and dilatation of the pupil. When the third nerve is divided, the
pupil dilates ; it dilates still more when atropine is administered after
the operation. Dropped into one eye in small quantity, atropine only
produces a local effect; the pupil of the other eye remains of normal
size, or somewhat constricted on account of the greater reflex stimula-
tion of its third nerve by the greater quantity of light now entering the
widely-dilated pupil of the atropinized eye. Even in the excised eye
the effect of the drug is the same. Introduced into the blood atropine
causes both pupils to dilate. Its action is to paralyze the endings of
the oculo-motor fibres to the sphincter pupillae and ciliary muscle.
Other mydriatic, or pupil-dilating drugs, are cocaine, daturine, and
hyoscyamine. Physostigmine or eserine, pilocarpine, and muscarine are
the chief miotics, or pupil-constricting substances. They also cause
spasm of the ciliary muscle, and inability to accommodate for distant
objects. They act by stimulating the structures (nerve-endings) (see
pp. 182, 739) which atropine paralyzes. The work of the mydriatics
can be undone by the miotics. Thus the dilatation produced by atro-
pine is removed by pilocarpine.
Functions of the Iris. — In vision the iris performs two chief
functions: (i) It regulates the quantity of light allowed to fall
upon the retina. The larger the aperture of a lens, the greater is
its collecting power, the more light does it gather in its focus. In
the eye, the area of the pupil determines the breadth of the pencil
of light that falls upon the lens. If this area was invariable, the
retina would either be ' dark from excess of light ' in bright sunshine,
or dark from defect of light in dull weather or at dusk. In ordei
that the iris may act as an efficient diaphragm it must be pig-
mented, and it is the pigment in it which gives the colour to the
normal eye. The vision of albinos, in whose eyes this pigment is
wanting, is often, though not invariably, deficient in sharpness.
There is always intolerance of bright light; and the same is true
in the condition known as irideremia, or congenital absence or
defect of the iris.
VISION
1027
(2) Another, and perhaps equally important, function of the iris
is to cut off the more divergent rays of a pencil of light falling upon
the eye, and thus to increase the sharpness of the image. This
leads us to the consideration of certain defects in the dioptric
arrangements of the eye.
Defects of the Eye as an Optical Instrument. — (i) Spherical Aberra-
tion.— It is a property of a spherical refracting surface that rays of
light passing through the peripheral portions are more strongly refracted
than rays passing near the principal axis. Hence a luminous point
is not focussed accurately in a single point by a spherical lens ; the image
is surrounded by fainter circles of light, the so-called circles of diffusion
representing the rays which have not yet come to a focus, or having been
already focussed have crossed and are now diverging. In the eye this
spherical aberration is partly corrected by the interposition of the iris,
which cuts off the more peripheral rays, especially in accommodation
for a near object, when they are most divergent. In addition, the
anterior surfaces of the cornea and Jens are not segments of spheres, but
of ellipsoids, so that the curvature diminishes somewhat with the dis-
tance from the optic axis,
and, therefore, the re-
fracting power as we pass
away from the axis does
not increase so rapidly
as it would do if the
surfaces were truly
spherical. Further, the
refractive index of the
peripheral parts of the
lens is less than that of
its central portions. Fig 423 .—Spherical Aberration. Rays passing
(2) Chromatic Aberra- through the more peripheral parts of a biconvex
tion. — All the rays of the lens L && brought to a focus F nearer the lens than
spectrum do not travel F', the focus of rays passing through the central
with the same velocity portions of the lens,
through a lens, and are,
therefore, unequally refracted by it, the short violet rays being focussed
nearer the lens than the long red rays. It was at one time supposed that
this chromatic aberration, as it is called, is compensated in the eye; and
it is said that this mistake gave the first hint that Newton's dictum as
to the proportionality between deviation and dispersion was erroneous,
and led to the discovery of achromatic lenses. But in reality the eye
is not an achromatic combination; and the violet rays are focussed
about J mm. in front of the red. Thus, in Fig. 424 the white light
passing through the lens is broken up into its constituents: the violet
focus is at V, and the red at R, behind it. A screen placed at R would
show not a point image, but a central point surrounded by concentric
circles of the spectral colours, with violet outside. If the screen was
placed at V, the centre would be violet and the red would be external.
For this reason it is impossible to focus at the same time and with perfect
sharpness objects of different colours : a red light on a railway track
appears nearer than a blue light, partly perhaps for the reason that it is
necessary to accommodate more strongly for the red than for the blue,
and we associate stronger accommodation with shorter distance of the
object, although other data are also involved in such a visual judgment.
When we look at a white gas-flame through a cobalt glass, which allows
only red and violet to pass, we see either a red flame, surrounded by a
1028
THE SENSES
violet ring, or a violet flame surrounded by a red ring, according as we
focus for the red or for the violet rays. But the dispersive power of
the eye is so small, and the capacity of rapidly altering its accommoda-
tion so great, that no practical inconvenience results from the lack of
achromatism, which, however, may be easily demonstrated by looking
at a pattern such as that in Fig. 425 at a distance too small for exact
accommodation .
It is also reckoned among the optical imperfections of the eye (3) that
the curved surfaces of the cornea and lens do not form a ' centred ' system
— that is to say, their apices and their centres of curvature do not all
lie in the same straight line; (4) that the pupil is eccentric, being
situated not exactly opposite the middle of the lens and cornea, but
nearer the nasal side, and that in consequence the optic axis, or straight
line joining the centres of curvature of the lens and cornea, does not
coincide with the visual axis, or straight line joining the fovea centralis
with the centre of the pupil, which is also the straight line joining the
centre of the pupil and any point to which the eye is directed in vision.
The angle between the optic and visual axis is about 5° (Fig. 416).
i£. 424. — Chromatic Aberration. The violet
rays are brought to a focus V nearer the lens
than R, the focus of the red rays.
Fig. 425. — To show Dispersion in
Eye (v. Bezold). View the
figure from a distance too small
for accommodation. Approach
the eye towards it; the white
rings appear bluish owing to
circles of dispersion falling on
them — i.e., circles of light of
different colours due to the
decomposition of white light
into its spectral constituents by
the media of the eye. A little
closer, and the black rings be-
come white or yellowish-white.
(5) Muscse volitantes, the curious bead-
like or fibrillar forms that so often flit
in the visual field when one is looking
through a microscope, are the token that
the refractive media of the eye are not
perfectly transparent at all parts ; they seem to be due to floating opacities
in the vitreous humour, probably the remains of the embryonic cells from
which the vitreous body was developed. (6) Lastly, it may be men-
tioned that slight irregularities in the curvature of the lens exist in all
eyes, so that a point of light, like a star or a distant street-lamp, is not
seen as a point, but as a point surrounded by rays (irregular astigma-
tism). In bringing this review of the imperfections of the dioptric
media of the normal eye to a close, it may be well to explain that what
are defects from the point of view of the student of pure optics are not
necessarily defects from the freer standpoint of the physiologist, who
surveys the mechanism of vision as a whole, the relations of its various
parts to one another and to the needs of the organism it has to serve,
the long series of developmental changes through which it has come
to be what it is, and the possibilities, so far as we can limit them, that
were open to evolution in the making of an eye. The optician may
perhaps assert, and with justice, that he could easily have made a better
lens than Nature has furnished, but the physiologist will not readily
admit that he could have made as good an eye.
VISION 1029
While the defects hitherto mentioned are shared in greater or
less degree by every normal eye, there are certain other defects
which either occur in such a comparatively small number of eyes,
or lead to such grave disturbances of vision when they do occur,
that they must be reckoned as abnormal conditions. In the normal
or emmetropic eye, parallel rays— and for this purpose all rays
coming from an object at a distance greater than 65 metres may be
considered parallel — are brought to a focus on the retina without
any effort of accommodation. The distance at which objects can
be distinctly seen is only limited by their size, the clearness of the
atmosphere, and the curvature of the earth; in other words, the
punctum remotum, or far-point of vision, the most distant point at
which it is possible to see with distinctness, is practically at an
infinite distance. When accommodation is paralyzed by atropine,
only remote objects can be clearly seen. On the other hand, the
normal eye, or, to be more precise, the normal eye of a middle-aged
Fig. 426. — Refraction in the (Normal) Emmetropic Eye. The image P' of a distant
point P falls on the retina when the eye is not accommodated. To save space,
P is placed much too near the eye in Figs. 426, 427.
adult, can be adjusted for an object at a distance of not more than
12 cm. (or 5 inches). Nearer than this it is not possible to see
distinctly; this point is accordingly called the punctum proximum
or near-point. The range of accommodation for distinct vision
in the emmetropic eye is from 12 cm. to infinity.
Myopia, or short-sightedness, is generally due to the excessive
length of the antero-posterior diameter of the eyeball in relation
to the converging power of the cornea and the lens. Even in
the absence of accommodation, parallel rays are not focussed on
the retina, but in front of it; and in order that a sharp image may
be formed on the retina the object must be so near that the rays
proceeding from it to the eye are sensibly divergent — that is to
say, it must be at least nearer than 65 metres — but as a rule an
object at a distance of more than 2 to 3 metres cannot be distinctly
seen. With the strongest accommodation the near-point may be
as little as 3 cm. from the eye. The range of vision in the myopic
1030
THE SENSES
eye is therefore very small. The defect may be corrected by con-
cave glasses, which render the rays more divergent. It is to be
noted that many cases of internal squint in children are connected
with myopia, the eyes necessarily rotating inwards as they are made
to fix an abnormally near object. The treatment both of the squint
and the myopia in these cases is the use of concave spectacles
(Fig. 427). Myopia, although a condition that shows a distinct
Fig. 427. — Myopic Eye. The image P' of a distant point P falls in front of the retina
even without accommodation. By means of a concave lens L the image may be
made to fall on the retina (dotted lines).
hereditary tendency, is rarely present at birth; the elongation of the
antero-posterior diameter of the eyeball develops gradually as the
child grows.
In hypermetropia, or long-sightedness, the eye is, as a rule, too
short in relation to its converging power; and with the lens in the
position of rest, parallel rays would be focussed behind the retina.
Accordingly, the hypermetropic eye must accommodate even for
Fig. 428. — Hypermetropic Eye. The knage P' of a point P falls behind the retina
in the unaccommodated eye. By means of a convex lens L it may be focussed
on the retina without accommodation (dotted lines).
distant objects, while even with maximum accommodation an
object cannot be distinctly seen unless it is farther away than the
near-point of the emmetropic eye. The far-point of distinct vision
is at the same distance as in the emmetropic eye — viz., at infinity —
the near-point is farther from the eye. The defect is corrected by
convex glasses (Fig. 428). Hypermetropia, unlike myopia, is
present at birth.
VISION 1031
Presbyopia, or the long-sightedness of old age, is not to be con-
founded with hypermetropia. It is essentially due to failure in
the power of accommodation, chiefly through weakness of the
ciliary muscle, but partly owing to increased rigidity and loss of
elasticity of the lens. Images of distant objects are still formed
on the retina of the unaccommodated eye with perfect sharpness —
i.e., the far-point of vision is not affected. But the eye is unable
to accommodate sufficiently for the rays diverging from an object
at the ordinary near-point ; in other words, the near-point is farther
away than normal. Convex glasses are again the remedy.
The near-point of distinct vision can be fixed in various ways —
among others, by means of Scheiner's experiment (Practical
Exercises, p. 1103). Two pin-holes are pricked in a card at a dis-
tance less than the diameter of the pupil. A needle viewed through
the holes appears single when it is accommodated for, double if it
is out of focus. The near-point of vision is the nearest point at
which the needle can still, by the strongest effort of accommoda-
tion, be seen single.
Astigmatism. — It has been mentioned that slight differences of
curvature along different meridians of the refracting surfaces exist
in all eyes. But in some cases the difference in two meridians at
right angles to each other is so great as to amount to a serious
defect of vision. To this condition the name of ' astigmatism ' or
' regular astigmatism ' has been given. It is usually due to an
excess of curvature in the vertical meridians of the cornea, less fre-
quently in the horizontal meridians; occasionally the defect is in
the lens. Rays proceeding from a point are not focussed in a point,
but along two lines, a horizontal and a vertical, the horizontal
linear focus being in front of the other when the vertical curvature
is too great, behind it when the horizontal curvature is excessive.
The two limbs of a cross or the two hands of a clock when they are
at right angles to each other cannot be seen distinctly at the same
time, although they can be successively focussed. The condition
may be corrected by glasses which are segments of cylinders cut
parallel to the axis (Practical Exercises, p. 1105).
The Ophthalmoscope. — The pupil of the normal eye is dark, and
the interior of the eye invisible, without special means of illu-
minating it. But this is not because all the light that falls upon the
fundus is absorbed by the pigment of the choroid, for even the pupil
of an albino appears dark when the eye is covered by a piece of
black cloth with a hole in front of the pupil. The explanation is
as follows :
Let the rays from a luminous point, P, be focussed by the lens,
L, at P' (Fig. 429). It is plain that rays proceeding from P' will
exactlv retrace the path of those from P and be focussed at P.
Now, the eye receives rays from all directions, and, when it is
1032
THE SENSES
sufficiently well illuminated, sends rays out in all directions. The
moment, however, that the observing eye is placed in front of the
observed eye, the latter ceases to receive light from the part of the
field occupied by the pupil of the former, and therefore ceases to
reflect light into it.
This difficulty is avoided by the use of an ophthalmoscopic
mirror. The original, and theoretically the most perfect, form of
such a mirror is a plate,
or several superposed
plates, of glass, from which
a beam of light from a
laterally placed candle or
lamp is reflected into the
observed eye, and through
Fig. 429. which the eye of the ob-
server looks (Fig . 430).
But the illumination thus obtained is comparatively faint ; and a
concave mirror is now generally used. In the centre is a small
hole or a small unsilvered portion of the mirror for the observer's
eye. In the direct method of examination (Fig. 432), the mirror
is held close to the observed eye, and an erect virtual image of
Fig. 430. — Figure to illustrate the Principle of the Ophthalmoscope. Rays of light
from a point are reflected by a glass plate M (several plates together in Helm-
holtz's original form) into the observed eye E1. Their focus would fall, as shown
in the figure, at P, a little behind the retina of E1. The portion of the retina
AB is therefore illuminated by diffusion circles; and the rays from a point of
it F will, if E1 is emmetropic and unaccommodated, issue parallel from E1 and
be brought to a focus at F1 on the retina of the (emmetropic and unaccommo-
dated) observing eye E.
the fundus is seen. When the eye of the observer and of the
patient are both emmetropic, and both eyes are unaccommodated,
the rays of light proceeding from a point of the retina of the
observed eye are rendered parallel by its dioptric media, and are
again brought to a focus on the observer's retina.
If the observed eye is myopic, the rays of light coming from
VISION
a point of the retina leave the eye, even when it is unaccommo-
dated, as a convergent pencil; and the emmetropic non-accom-
modated eye of the observer must have a concave lens placed
before it in order that the fundus may be distinctly seen.
When the observed eye is hyper-
metropic, the rays emerging from the
unaccommodated eye are divergent,
and a convex lens, the strength of
which is proportional to the amount
of hypermetropia, must be placed
before the observer's unaccommo-
dated eye if he is to see the fundus
distinctly. By accommodating, the
observer can see the fundus clearly
without 'a convex lens.
By this method errors of refraction
in the eye may be detected and
measured. The observer must always
keep his eye unaccommodated, and
if it is not emmetropic, he must
know the amount of his short- or
long-sightedness — i.e., the strength
and sign of the lens needed to correct
his defect of refraction, and must
allow for this in calculating the defect of his patient. Non-
accommodation of the eye of the latter can always be secured by
the use of atropine.
Fig. 431.— May's Electric Ophthal-
moscope.
Fig. 432, — Direct Method of using the Ophthalmoscope. Light falling on the per-
forated concave mirror M passes into the observed eye E' ; and, both E' and the
observing eye E being supposed emmetropic and unaccommodated, an erect
virtual image of the illuminated retina of E' is seen by E.
By the direct method of ophthalmoscopic examination, only a
small portion of the retina can be seen at a time, and this is highly
magnified. A larger, though less magnified, view can be got by
the indirect method. The observed eye is illuminated as before,
1034
THE SENSES
but the mirror and the observer's eye are at a greater distance
(Fig. 435). Here the rays from a considerable portion of the
retina are brought to a focus by a convex lens held near the eye
of the patient, so as to form a real and inverted aerial image of the
Fig. 433. — Use of the Ophthalmoscope (Direct Method) for testing Errors of Re-
fraction in Myopic Eye. Rays issuing from a point of the retina of E', the
observed (myopic and unaccommodated) eye, pass out, not parallel, but con-
vergent. They will therefore be focussed in front of the retina of the observing
(unaccommodated) eye E if the latter is emmetropic. By introducing a concave
lens L of suitable strength, however, a clear view of the retina of E' will be
obtained, and the strength of this lens is the measure of the amount of myopia.
retina. This image is viewed by the observer at his ordinary visual
distance. It is not necessary in this method that the observed
eye should be non-accommodated, although it is convenient as in
Fig. 434. Testing Errors of Refraction in Hypermetropic Eye. Rays from a point
of the retina of E', the observed eye, issue divergent, and are focussed behind
the retina of the observing (unaccommodated and emmetropic) eye E. The
strength of the convex lens L, which must be introduced in front of E to give
clear vision of the retina of E', measures the degree of hypermetropia.
the direct method to cause dilatation of the pupil by atropine, which
also relaxes the accommodation (Practical Exercises, p. 1108).
Skiascopy. — To a great extent the ophthalmoscopic method of
measuring errors of refraction has been replaced by the more modern
VISION
i°35
method of skiascopy (shadow test). It depends upon the following
observation: When one throws light from a little distance with a
concave mirror into an observed eye and then rotates the mirror
slowly around the long axis of the handle, one sees that the pupil,
which at first was completely illuminated, becomes dark from one
side as if covered by a shadow. This shadow will move in the same
direction in which the mirror is rotated or in the opposite direction,
according to whether the observer is farther from the observed eye
than its far-point, or between the eye and the far-point. If the
observer is exactly at the far-point, no direction of movement of
the shadow can be made out, but the pupil in its whole extent is
Fig. 435. — Indirect Method of using the Ophthalmoscope. The rays of light issuing
from E', the observed eye, are focussed by the biconvex lens L, and a real inverted
image of a portion of the retina of E ', magnified four or five times, is formed in
the air between the lens and the observing eye E. This image is viewed by E
at the ordinary distance of distinct vision (10 to 12 inches). (The exaggeration
of the size of the mirror makes it appear as if some of the rays from the lamp
passed through the lens before being reflected from the mirror. This would not
be the case in an actual observation.)
either illuminated or altogether dark. In this way the distance
of the far-point of a myopic eye can be easily determined by a
metre rule, and from this the degree of myopia. If the far-point
is either too near, as in strong myopia, or too distant, as in weak
myopia and emmetropia, or behind the observed eye, as in hyper-
metropia, it can be brought to a convenient distance by interposing
suitable lenses. The observer then determines the far-point exactly
by moving his eye nearer to or farther from the observed eye,
or, keeping his own eye fixed, by bringing the far-point of the
observed eye to coincide with it by inserting lenses (Practical
Exercises, pp. 1109, mo).
1036
THE SENSES
The phenomenon depends upon the interruption which the light pro-
ceeding from the observed retina experiences first at the margin of the
pupil of the observed eye, and then at the margin of the hole in the
mirror or of the observer's pupil. When the mirror is rotated, an illu-
minated point of the observed retina will move in the opposite direction
over the retina.* The light proceeding from this point when the
observed eye is emmetropic is so refracted by the lens and cornea that
it leaves the eye as a bundle of parallel rays in the direction of the
image of the source of light (I/) (Fig. 436). If the image of the flame
reflected by the mirror is situated on the principal axis of the observer's
eye, and if the pupils of observed and observer are of equal size, all
the rays coming from the observed retina will fall on the observer's
retina, and therefore the whole pupil of the observed eye will appear
light. If the mirror is now rotated so that the image of the source of
light moves away from the principal axis, and the illuminating rays are
no longer in that axis, the illuminated point will move in the opposite
direction from the principal axis, and the light returning from the pupil
of the observed eye will again issue in the direction of the image of the
Fig. 436.— Path of Rays in Skiascopy (Snellen). V, observed eye; Be, eye of ob-
server; Sf>, mirror; L, source of light; L', image of the source of light; A, A',
principal axis ; P, P', pupils.
source of light. It can then happen that none of the rays hit the
observer's pupil, and the observed pupil will appear entirely dark. Or
the direction of the rays may be such that a portion of them enters the
observer's pupil, the rest being interrupted by its border. In this case
the part of the observed pupil from which rays enter the observer's
pupil will appear light, while the rest is dark. From Fig. 436 it can be
seen that the light part of the observed pupil is on the opposite side of
the principal axis from the image of the source of light. If, therefore,
the image of the source of light moves to the right (by rotation of a
concave mirror to the right, or rotation of a plane mirror to the left)
the skiascopic appearance in the observed pupil moves to the left — i.e.,
in the opposite direction to the image of the source of light.
If the observed pupil is myopic — i.e., if its far-point is between the
observer and the observed eye, rotation of the mirror so far from the
principal axis that only a part of the rays issuing from the observed
pupil enter the observer's eye, will cause the pupil to appear light only
• When a concave mirror is rotated to the right, the inverted real mirror
image also moves to the right, and the illuminated point to the left. When
a plane mirror is rotated to the right, the virtual mirror image moves to the
left, and the illuminated point on the retina therefore to the right.
VISION
1037
on ojle side, and on account of the crossing of the rays this illuminated
portion will be on the same side of the principal axis as the image ol
the source of light (Fig. 437). When the image of the source of light is
moved to the right the light area of the observed pupil will also move
to the right — i.e., with rotation of a concave mirror in the same direction
as the image of the source of light, and with rotation of a plane mirror
in the opposite direction (Snellen).
A method of photographing the retina in the living eye has also been
employed as a means of investigating the fundus.
Single Vision with Both Eyes — Diplopia. — Scheiner's experiment shows
that it is possible to have double vision, or diplopia, with a single eye
when two separate images of the same object fall upon different parts
of the retina. In vision with both eyes, or binocular vision, an image
of every object looked at is, of course, formed on each retina, and we
have to inquire how it is that as a rule these images are blended in
consciousness so as to produce the perception of a single object; and
A —
Fig. 437. — Path of Rays in Skiascopy (Myopic Eye) (Snellen). PR, far -point ol
observed eye. The other references are as in Fig. 436.
how it is that under certain conditions this blending does not take
place, and diplopia results. Two chief theories have been invoked in
the attempt to answer these questions: (i) the theory of identical
points, (2) the theory of projection.
In regard to the second theory, we shall merely say that it assumes
that in some way or other the retina, or, rather, the retino-cerebral
apparatus, has the power of appreciating not only the shape and size
of an image, but also the direction of the rays of light which form it,
and that the position of the object is arrived "at by a process of mental
projection of the image into space along these directive lines. Where
the directive lines of the two eyes cut each other, the two images coin-
cide, and the object is seen single in the position of the point of inter-
section. The first theory we shall examine in some detail.
The Theory of Identical Points. — This theory assumes that every
point of one retina ' corresponds ' to a definite point of the other retina,
and that in virtue of this correspondence, either by an inborn necessity
or from experience, the mind refers simultaneous impressions upon two
corresponding or identical points to a single point in external space.
If we imagine the two retinae in the position which the eyes occupy
when fixing an infinitely distant object — that is, with the visual axes
parallel — to be superposed, with fovea over fovea, every point of the
one retina will be covered by the corresponding point of the other
retina, so that identical points could be pricked through with a needle.
10J8 THE SENSES
But since the actual centre of the retina does not correspond with the
fovea centralis (Fig. 416), but lies nearer the nasal side, the nasal edge
of the left retina will overlap the temporal edge of the right, and the
nasal edge of the right will overlap the temporal edge of the left; so
that a part of each retina has no corresponding points in the other.
The adherents of this theory claim, and with justice, that a small
object so situated that its image must be formed on corresponding
points of the two retinae does, as a rule, appear single, and, what is even
more striking, that a phosphene, or luminous ring produced by pressing
the blunt end of a pencil or the finger-nail on a point of the globe of one
eye (which Newton compared to the circles on a peacock's tail), is not
doubled by pressure over the corresponding point of the other eye,
although two circles are seen when pressure is made upon points which
do not correspond. Jf in rotating the eyes one eye is prevented by
pressure with the finger from following the movement of the other,
there is double vision. When strabismus or squinting is produced by
paralysis of the third (p. 924) or the sixth cranial nerve (p. 926), it is
accompanied by diplopia, until in course of time the mind iearns to
disregard one of the images. In some cases of squint the double images
are never completely suppressed, but a new abnormal form of visual
localization is developed, which, however, very seldom permits any
accurate judgment of depth. In strabismus it is obvious that the two
images of an object cannot fall on corresponding points.
But it is also a fact that, under certain conditions, images situated
on corresponding points may not, and that images not situated on
corresponding points may, give rise to a single impression. For ex-
ample, if one of the closed eyes be held slightly out of its ordinary
position by the finger, pressure on identical points of the two eyes gives
rise to two separate phosphenes. And some of the phenomena of stere-
oscopic vision (p. 1039) show clearly that images falling on points not
strictly corresponding may give a single impression; while we do not
habitually see double, although it is certain that the images of multi-
tudes of objects are constantly falling on points of the retinae not ana-
tomically ' identical.'*
The question therefore arises, How is it that we do not see these
double images? This is one of the difficulties of the theory of identical
points. The following is a partial explanation: (i) The images of
objects in the portion of the field most distinctly seen — that is, the
portion in the immediate neighbourhood of the intersection of the
visual lines, or the part to which the gaze is directed — are formed on
identical points; and by rapid movements the eyes fix successively
different parts of the field of view. (2) Vision grows less distinct as
we pass out from the centre of the retina, and we are accustomed to
neglect the blurred peripheral images in comparison with those formed
* In every fixed position of the eyes, the objects whose images fall on
corresponding points will be arranged on certain definite lines or surfaces
which vary with the direction of the visual axis and to which the name of
horopter, or point-horopter, has been given. For most eyes when directed
to the horizon — that is, with the visual axes parallel — the horopter is practi-
cally the horizontal plane of the ground, so that all objects within the field
of vision, and resting on the ground, fall upon corresponding points, and are
seen single. When the eyes are directed to a point at such a distance that
the lines of vision are sensibly convergent, the horopter consists (i) of a
straight line drawn through the fixing-point and at right angles to a plane
passing through the fixing-point and the two visual lines (visual plane) ; (2) of
a circle passing through the fixing-point and the nodal points of the two eyes
(the famous horopteric circle of Miiller).
on the fovea. (3) When the images of an object do not fall on identical
points, one of the points on which they do fall may be occupied with
the images of other objects, some of which may be so boldly marked
as to enter into conflict with the extra image and to suppress it.
(4) Lastly, the physiological ' identical pornt ' is not a geometrical
point, but an area which increases in size in tiis more peripheral zones
of the retina, and can also be increased by practice; and images which
lie wholly or in chief part within two corresponding areas practically
coincide.
Stereoscopic Vision. — Although the retinal image is a projection of
external objects on a surface, we perceive not only the length and
breadth, but also the depth or solidity of the things we look at. When
we look directly at the front of a build-
ing, the impression as to its form is the
same whether one or both eyes be used,
although with a single eye its distance
cannot be judged so accurately. But
when we view the building from such a
position that one of the corners is visible,
we obtain a more correct impression of
its depth with the two eyes. This is
partly due to the fact that to fix points
at different distances from the eyes the
visual lines must be made to converge
more or less, and of the amount of this
convergence we are conscious through
the contraction of the muscles which
regulate it. But there is another element
involved. When the two eyes look at a
uniformly - coloured plane surface, the
retinal image is precisely the same in
both. But when the two eyes are
directed to a solid object (say a book
lying on a table) the picture formed on
the left retina differs slightly from that
formed on the right, for the left eye sees
more of the left side of the book, and
the right eye more of the right side.
That there is a close connection be-
tween uniformity of retinal images and
impression of a plane surface on the one
hand, and difference of retinal images and
impression of solidity on the other, is
pjroved by the facts of stereoscopy. It
is evident that if an exact picture of the solid object as it is seen by
each eye can be thrown on the retina, the impression produced will
be the same, whether these images are really formed by the object
or not. Now, two such pictures can be produced with a near approach
to accuracy by photographing the object from the point of view of
each eye. It only remains to cast the image of each picture on the
corresponding retina, while the eyes are converged tc the same extent
as would be the case if they were viewing the actual object. This is
accomplished by means of a stereoscope (Fig. 438).
It is found that the resultant impression isithat of the solid object.
It is impossible to reconcile this with the doctrine of strictly identical
geometrical points. A pair of identical pictures gives with the stere-
oscope not the impression of a solid, but of a plane surface. If the
Fig. 438. — Brewster's Stereoscope.
p and TT are prisms, with their re-
fracting angles turned towards
each other. The prisms refract
the rays coming from the points
c, y of the pictures ab and a/3 so
that they appear to come from a
single point q. Similarly, the
points a and appear to be situ-
ated at/, and the points b and /3,
at a.
ro4o THE SENSES
relative position of any two points differs in the two pictures, the
blended picture has a corresponding point in relief. So great is the
delicacy of this test that a good and a bad banknote will not blend
under the stereoscope to a flat surface, and the method may be actually
used for the detection of forgery.
When the pictures are interchanged in the stereoscope so that the
image which ought to be formed on the right retina falls on the left, and
that which is intended for the left eye falls on the right, what were
projections before become hollows, and what were hollows stand out
in relief. The pseudoscope of Wheatstone is an arrangement by which
each eye sees an object by reflection, so that the images which would be
formed on the two retina?, if the object were looked at directly, are inter-
changed, with the same reversal of our judgments of relief.
Visual Judgments. — We say judgments of relief; for what we call
seeing is essentially an act that involves intellectual processes. As the
retina is anatomically and developmentally a projection of the brain
pushed out to catch the waves of light which beat in upon the organism
from every side, so, physiologically, retina, optic nerve, and visual
nervous centre are bound together in an indissoluble chain. We
cannot say that the retina sees, we cannot say that the optic nerve
sees — the optic nerve in itself is blind — we cannot say that the visual
centre sees. The ethereal waves falling on the retina set up impulses
in it which ascend the optic nerve; certain portions of the brain are
stirred to action, and the resulting sensations of light springing up, we
know not where, are elaborated, we know not how (by processes of
which we have not the faintest guess), into the perception of what we
call external objects — trees, houses, men, parts of our own bodies, and
into judgments of the relations of these things among themselves, of
their distance and movements.
A child learns to see, as it learns to speak, by a process, often un-
conscious or subconscious, of ' putting two and two together.' The
musical sounds united and terminated by noises which make up the
spoken word ' apple ' are gradually associated in its mind with the
visual sensation of a red or green object, the tactile sensation of a
smooth and round object, and the gustatory and olfactory sensations
which we call the taste or flavour of an apple. And as it is by ex-
perience that the child learns to label this bundle of sensations with a
spoken, and afterwards with a written, name, so it is by experience
that it learns to group the single sensations together, and to make the
induction that if the hand be stretched out to a certain distance and in
a certain direction — i.e, if various muscular movements, also associated
with sensations, be made — the tactile sensation of grasping a smooth
round body will be felt, and that if the further muscular movements
involved in conveying it to the mouth be carried out, a sensation agree-
able to the youthful palate will follow. At length the child comes to
believe, and, unless he happens to be specially instructed, carries his
belief with him to his grave, that when he looks at an apple he sees a
round, smooth, tolerably hard body, of definite size and colour; while
in reality all that the sense of sight can inform him of is the difference
in the intensity and colour of the light falling on his retina when he
turns his head in a particular direction.
An interesting illustration of the role of experience in shaping
our visual judgments is found in the sensations of persons born
blind and relieved in after-life by operation. A boy between
thirteen and fourteen years of age, operated on by Cheselden,
VISION
1041
thought all the objects he looked at touched his eyes. He forgot
which was the dog and which the cat, but catching the cat (which
he knew by feeling), he looked at her steadfastly and said, " So,
puss, I shall know you another time." Pictures seemed to him only
parti-coloured planes; but all at once, two months after the opera-
tion, he discovered they represented solids.' Nunnely, perhaps
remembering the dictum of Diderot, that ' to prepare and interro-
Fig. 439. — Illusion of Parallel Lines (Hering).
gate a person born blind would not have been an occupation un-
worthy of the united talents of Newton, Des Cartes, Locke, and
Leibnitz,' made an elaborate investigation in the case of a boy nine
years old, on whom he operated for congenital cataract of both eyes,
and, what is of special importance, instituted a set of careful
experiments and interrogations before the operation, so as to gain
data for comparison. Objects (cubes and spheres) which before
the operation he could easily recognize by touch were shown him
afterwards, but al-
though ' he could at
once perceive a differ-
ence in their shapes,
he could not in the
least say which was
the cube and which
the sphere.' It took
several days, and the
objects had to be
placed many times in
his hands before he
could tell them by
the eye. ' He said everything touched his eyes, and walked most
carefully about, with his hands held out before him to prevent
things hurting his eyes by touching them/
Many other illustrations might be given of the fact that ' seeing '
is largely an act of reasoning from data which may sometimes
mislead. Thus in Figs. 439 and 440 the long horizontal lines are
really parallel, but do not appear so owing to the confusion of
judgment produced by the short sloping lines. In Fig. 441 the
spaces covered by A, B, and C are equal squares, but A appears
66
XXXUXUXXXXIXUXK
MMffffffSffffU
mxxxxxuxxxxxxxxi
Fig. 4 to. — Illusion of Parallel Lines (Zcllner).
1042
THE SENSES
<° >
taller than B, and C smaller than either A or B. In the same
figure the lines D and E are of the same length, but E seems con-
siderably longer than D.
Illusions of movement are among the most interesting optical
illusions. If two similar objects are momentarily shown to the
eye in rapid succession and at points in space not separated by too
great a distance, the illusion is produced that the first object has
moved to the position of the second. Such illusions are the basis
of the so-called ' moving pictures ' shown by the cinematograph.
A series of instantaneous photographs of a movement are taken,
recording the successive positions assumed by the moving body.
When these are thrown on the retina in the same order and in rapid
succession, an illusion of the original movement is produced.
The apparent size and form of an object is intimately related to
the size, form, and sharpness of its image on the retina. We are,
therefore, able to dis-
A B C criminate with great
precision the un-
stimulated from the
excited portions of
that membrane, es-
pecially in the fovea
centralis, and also
the degree of excita-
tion of neighbouring
excited parts. But
instead of localizing the image on the retina as we localize on the
skin the pressure of an object in contact with it, we project the
retinal image into space, and see everything outside the eye.
In vision, in fact, we have no conception of the existence of either
retina or retinal image; and even the shadows of objects within the
eye — for instance, an opacity or a foreign body in any of the refractive
media — are referred to points outside it. Generally opacities in the
vitreous humour are movable, in the lens not.
Purkinje's Figures. — As was first pointed out by Purkinje, the
shadows of the bloodvessels in the retina itself, and even of the
corpuscles circulating in them, although neglected in ordinary
vision, may be recognized under suitable conditions, a conclusive
proof that the sensitive layer must lie behind the vessels.
If a beam of sunlight is concentrated on the sclerotic as far as possible
from the margin of the cornea, and the eye directed to a dark ground,
the network of retinal bloodvessels will stand out on it. Another
method is to look at a dark ground while a lighted candle, held at one
side of the eye at a distance from the visual line, is moved slightly to
and fro. In the first method, a point of the sclerotic behind the lens
is illuminated, and rays passing from it across the interior of the eyeball
in every direction cast shadows of the vessels of the retina on its sensi-
Fig. 441. — Illusions of Space-Perception.
VISION
1043
tive layer. In the second method, the image of the flame formed on
the retina by rays falling obliquely through the pupil becomes in the
general darkness itself a source of light, by interrupting the rays from
which the retinal vessels form shadows. The distance of the sensitive
from the vascular layer may be approximately calculated by measuring
the amount by which the shadows change their position, when the
position of the illuminated point of the sclerotic is altered. The nearer
a vessel lies to the sensitive layer, the smaller must be the angle through
which the apparent position of its shadow moves for a given move-
ment of the spot of light. In this way it has been calculated that the
sensitive layer is about 0-2 to 0-3 mm. behind the Stratum which con-
tains the bloodvessels.
This corresponds suffi-
ciently well with the
position of the layer of
rods and cones, which all
other evidence shows to
be the portion of the
retina actually stimulated
by light. The shadows of
the blood -corpuscles in
the retinal vessels may be
rendered visible by look-
ing at a bright and uni-
formly illuminated ground,
like the milk glass shade
of a lamp or the blue sky,
and moving the slightly
separated fingers or a
perforated card rapidly Fig- 442.— Method of rendering the Retinal Blood-
before the eve From the vessels visible by concentrating a Beam of Light
on the Sclerotic. From the brightly-illuminated
point of the sclerotic, a, rays issue, and a shadow
of a vessel, v, is cast at a'. It is referred to an
external point, a", in the direction of the straight
line joining a' with the nodal point. When the
light is shifted so as to be focussed at b, the
shadow cast at b' is referred to b" — i.e., it appears
to move in the same direction as the illuminated
point of the sclerotic.
rate of their apparent
movement, Vierordt cal-
culated the velocity of the
blood in the retinal capil-
laries at 0*5 to 0-9 mm.
per second. One reason
why the shadows of these
intra-retinal structures do
not appear in ordinary
vision seems to be their small size. The retinal vessels are in reality
only vascular threads; the thickest branch of the central vein is not
A, mm. in diameter. The apex of the cone of complete shadow
(umbra) cast by a disc of this size, at a distance of 20 mm. from a pupil
4 mm. wide, would lie only \ mm. behind the disc — that is to say, the
umbra of the retinal vessels would not reach the layer of the rods and
cones at all, and only the penumbra, or region of relative darkness,
would fall upon it.
When the eyes, after being closed for some time, are suddenly opened,
the branches of the retinal vessels may be seen for a moment. This is
especially the case after sleep; and a good view of the phenomenon
may be obtained by looking at a white pillow or the ceiling immediately
on awaking. If the eyes are kept open for a few seconds, the branch-
ing pattern fades away; if they are only allowed to remain open for
an instant, it may be seen many times in succession. The main vessels
appear to radiate out from a central point. But their actual junction
there is not seen, since it lies in the optic disc or blind spot.
1044
THE SENSES
The Blind Spot. — The fibres of the optic nerve are insensible to
light; light only stimulates them through their end-organs. This
can be proved by directing by means of an ophthalmoscope a beam
of light upon the optic disc, where the true retinal layers do not
exist. The person experimented on has no sensation of light when
the beam falls entirely upon the disc ; when its direction is shifted
so that it impinges upon any other portion of the retina, a sensation
of light is at once experienced. The blind spot is not recognized
in ordinary vision, for (i) the two optic discs do not correspond.
The left disc has its corre-
sponding points on a sensitive
part of the right retina, and
the right disc on a sensitive
part of the left retina; and the
consequence is that in binoc-
ular vision the objects whose
images are formed on the cor-
responding points fill up the
blind spots. (2) The optic
disc does not lie in the line of
direct, and therefore distinct,
vision. The eye is constantly
moving so as to bring the
surrounding objects succes-
sively on the fovea centralis;
and the gap which the blind
spot makes in the visual field
of a single eye is thus more
easily neglected. In any case
we ought not to see it as a
dark spot, for darkness is only associated with the absence of
excitation in parts of the retina capable of being excited by light.
There is no more reason why the optic discs should appear dark
than there is for our having a sensation of darkness behind us when
we are looking straight in front. And since the experience of our
other senses — the sense of touch, for example — tells us that the
objects we look at do not in general have a gap in the position corre-
sponding to the part of the image that falls on the blind spot, we
see, so to speak, across the spot.
By Mariotte's experiment, however, the existence of the blind spot
can not only be demonstrated, but its size determined and its boundaries
mapped out. Let the left eye be closed, and fix with the right the small
cross ; then, if the eye be moved towards or away from the paper, keeping
the cross fixed all the time, a position will be found in which the white
disc disappears altogether. In this position its image falls on the
blind spot (Fig. 444).
Fig. 443- — Method of rendering the Blood-
vessels of the Retina visible by Oblique
Illumination through the Cornea. Light
from a candle at a illuminates a', and
rays proceeding from a' cast a shadow of
the bloodvessel, v, at a", which is referred
to a'". When a is moved to 6, the
shadow on the retina moves to b", and
the shadow in the visual field of the illu-
minated eye to b'".
VISION
1045
Relation of the Rods and Cones to Vision. — We have more than
once referred to the rods and cones as the sensitive layer of the
retina. It is now necessary to develop a little more the evidence
in favour of this statement. And at the outset, since the sensitive
layer has been shown to lie behind the plane of the retinal blood-
vessels, the only competitors of the rods and cones are the external
nuclear layer and the pigmented epithelium. The nuclear layer
may be at once excluded as a separate mechanism, since, as we have
seen (p. 1015), the portions of the rod and cone elements in it are
continuous with the portions in the layer of the rods and cones
proper. In the fovea centralis, where vision is most distinct, the
nuclear layer becomes very thin and inconspicuous.
The layer of pigmented hexagonal cells, or at least their pigment,
cannot be essential to vision, for albino rats, rabbits, and men, in
whose eyes pigment is absent, can see. In man and most mammals
there are cones, but no rods in the yellow spot and fovea centralis;
the relative proportion of rods increases as we pass out from the
fovea towards the ora serrata. But this does not enable us to
Fig. 444, — Mariotte's Experiment.
analyze the bacillary layer into sensitive cones and non-sensitive
rods, for on the rim of the retina, which is still sensitive to light,
there are only rods; in the bat and mole there are said to be. no
cones even in the yellow spot, in the rabbit very few. Reptiles
possess only cones over the whole retinal surface, and birds, true
to their reptilian affinities, have everywhere more cones than rods,
as have also fishes. .
One of the difficulties in the way of understanding how a ray of
light can set up an excitation in a rod or cones is the transparency
of these structures. An absolutely transparent substance — that
is, a substance which would allow light to traverse it without the
least absorption — would, after the passage of a ray, remain in
precisely the same state as before; its condition could not be
altered by the passage of the light unless some of the energy of the
ethereal vibrations was transferred to it. But an absolutely trans-
parent body does not exist in Nature; and it is not necessary to
suppose that all the energy required to stimulate the end-organs
of the optic nerve comes from the luminous vibrations. These
may, and probably do, act by setting free energy stored up in the
io46 THE SENSES
retina, just as the touch of a child's hand could be made to fire a
mine, or launch a ship, or flood a province. Some have looked upon
the transverse lamellae into which the outer members of the rods
and cones can be made to split as an arrangement for reflecting
back the light to the inner members, and have compared them
to a pile of plates of glass, which, transparent as it is, is a most
efficient reflector. It is even possible, although here we are already
treading the thin air of pure speculation, that the light may be
polarized in the process of reflection, and that the rods and cones
may be less transparent to light polarized in certain planes than to
unpolarized light.
As to the nature of the transformation undergone by the ethereal
vibrations in the rods and cones, various theories have been formu-
lated. Some have supposed that the absorbed light-waves are
transformed into long heat-waves, and that the endings of the optic
nerve are thus excited by thermal stimuli. This hypothesis has so
little evidence in its favour that it is perhaps an unjustifiable waste
of time even to mention it. It is ruled out of court by the mere fact
that the long radiations of the ultra red, filtered from luminous rays
by being passed through a solution of iodine, and focussed on the
eye by a lens of rock-salt, produce not the slightest sensation of
light, although they are by no means all absorbed in their passage
through the dioptric media. Again, it has been suggested that the
energy of the waves of light is first transformed into electrical energy,
and that the visual stimulus is really electrical. In support of
this view it has been urged that the passage of a voltaic current
through the eye causes sensations of light, and that light, un-
doubtedly, causes (p. 839) an electrical change in the retina and
optic nerve. But, as has more than once been pointed out, an
electrical change is the token and accompaniment of the activity
of the excitable tissues in general; and all that the currents of
action of the retina show is that light excites the retina — a proposi-
tion which nobody who can see requires an objective proof of, and
which does not carry us very far towards the solution of the
problem how that excitation is brought about. Then there is
the photo-mechanical theory, according to which the pigmented
epithelial cells of the retina, altering their shape and volume under
the stimulus of light, press upon the rods and cones, and thus
mechanically stimulate them. Lastly, there is the photo-chemical
theory, which supposes that some chemical change produced in the
rods and cones under the influence of light sets up impulses in them
which ascend the optic nerve. This is the most probable of ah1 the
theories, notwithstanding the fact that the discovery by Boll of
the famous visual purple or rhodopsin, which at first seemed likely
to place it upon a sure foundation, has lost its significance in this
regard. But although the visual purple is not a photo-chemical
VISION 1047
substance through which the retinal elements are excited by
luminous stimuli, it seems to fulfil an important function in adapt-
ing the retina — i.e., rendering it more sensitive — -for vision in dim
light. In any case, its discovery is in itself so interesting and so
suggestive as a basis for future work, that a short account of the
properties of the substance cannot be omitted here.
Visual Purple. — If the eye of a frog or rabbit, which has been kept
in the dark, be cut out in a dimly -lighted chamber or in a chamber
illuminated only by red light, and the retina removed, it is seen, when
viewed in ordinary light, to be of a beautiful red or purple colour.
Exposed to bright light, the colour soon fades, passing through red and
orange to yellow, and then disappearing altogether. The yellow colour
is due to the formation of another pigment, visual yellow; the preceding
stages are due to the intermixture of this visual yellow with the un-
changed visual purple in different proportions. With the microscope
it may be seen that the pigment is entirely confined to the outer segment
of the rods, where it exists in most vertebrate animals. It may be ex-
tracted by a watery solution of bile-salts, and the properties of the
pigment in solution are very much the same
as its properties in situ ; light bleaches the
solution as it does the retina. Examined with
the spectroscope, the solution shows no definite
bands, but only a general absorption, which is
very slight in the red, and reaches its maxi-
mum in the yellowish-green. In accordance
with this, it is found that of all kinds of mono-
chromatic light the yellowish -green rays bleach
the purple most rapidly, the red rays most
slowly.
If a portion of the retina is kept dark while
the rest is exposed to light only the latter p. 445._Optogram. Part
portion is bleached. And when the image of of retina of rabbit> the
an object possessing well-marked contrasts of eye Of which had been
light and shadow (e.g., a glass plate with strips directed to an illumin-
of black paper pasted on it at intervals, or a ated plate of glass cpv-
window with dark bars) is allowed to fall on an ered with strips of black
eye otherwise protected from light, the pattern paper.
of the object is picked out on the retina in
purple and white. A veritable photograph or ' optogram ' may thus be
formed even on the retina of a living rabbit; and if the eye be rapidly
excised, the picture may be ' fixed ' by a solution of alum, and thus
rendered permanent.
These facts certainly suggest that light falling on the retina may
cause in some sensitive substance or substances chemical changes,
the products of which stimulate the endings of the optic nerve,
and set up the impulses that result in visual sensations.
The visual purple cannot itself be such a substance, for it is
absent from the cones of all animals and the rods of some. Frogs
and rabbits can undoubtedly see at a time when, by continued
exposure to bright sunlight, the purple must have been completely
bleached. And although the alleged absence of the pigment in
the eye of the bat might seem to afford a ready explanation of the
1048 THE SENSES
proverbial ' blindness ' of that animal, such a hasty deduction
would be at once corrected by the fact that birds with as sharp
vision as the pigeon are equally devoid of visual purple, while in
other nocturnal animals, like the owl, it is plentifully found. The
most probable hypothesis of the function of the visual purple is
indeed that which attributes to it the property, in virtue of its
capacity for regeneration in the dark, of adapting the eye for night
or twilight vision — in other words, of increasing the sensitiveness
of the retina for faint light, especially of the shorter wave-lengths.
If this is the case, it is precisely in nocturnal animals that we should
expect to find it in large amount; and recently visual purple has
been obtained from more than one species of bat (Trendelenburg).
The fact that central vision (p. 1058) in which the rodless fovea is
concerned is but little, if at all, susceptible of dark-adaptation,
while peripheral vision shows a marked capacity of adaptation,
agrees well with this hypothesis. We shall see later that there is
some evidence that it is the mere perception of luminous impressions
as such and of their intensity, without any distinction of quality
or colour, with which the rods have to do. They are, then, on the
hypothesis under discussion, elements concerned in achromatic
sensations under conditions of feeble illumination (twilight vision).
The cones are supposed on this theory to be more highly developed
elements than the rods, their function being connected, especially
with the perception of colour, but also with the perception of
achromatic sensations under daylight conditions.
The pigmented retinal epithelium is undoubtedly sensitive to light,
and has important relations to the formation of the visual purple!
When the eye is exposed to light, black pigment migrates along the
processes of the epithelial cells between the rods, even as far as the
external limiting membrane. In the dark the pigment moves back
again, and gathers around the outer portions of the rods, where the
visual purple is being regenerated. That the central nervous system
is not concerned in the pigment migration, or at least that it is not
indispensable for it, has been shown in the larvae of Amblystoma, one
of the tailed amphibia. Optic cups were transplanted to various parts
of the body, where they developed to form more or less perfect eyes.
The forward movement of the pigment in these transplanted eyes when
exposed to light was fully as great as in the normal eyes. Contraction
of the cones was also observed in them just as in the normal eyes. In
the eye exposed to the light, the cones, whose expanded length is 251*
shortened by more than 4/1 (Laurens and Williams). The precise mean-
ing of the changes in the pigmented cells is obscure.
The pigmented epithelium is known to be concerned in the regenera-
tion of the visual purple. When a frog is curarized, cedema occurs
between the retina and the choroid, so that the former membrane is
separated from the hexagonal epithelium. If the frog is now exposed
to sunlight till the visual purple is bleached, and the retina then taken
out and placed in the dark, no regeneration of the purple takes place.
When the same experiment is repeated on a non-curarized frog, the
visual purple is restored in the dark, and may be seen under the micro-
scope in the rods. The only difference in the two experiments is that
in the latter the pigmented epithelium adheres to the retina, and it
VISION 1049
must therefore have a hand in the regeneration of the pigment. Ever,
the visual purple of a retina from which the epithelium has been de-
tached will, after being bleached, be restored if the retina is simply laid
again on the epithelial surface. And it does not seem to be the black
pigment of the hexagonal cells which is the agent in this restoration,
for it takes place in the pigment-free retinae of albino rabbits or rats.
Even a retina isolated from the pigmented epithelium, and then
bleached, may, to a certain extent, develop new visual purple in the
dark. This is even true when it has been kept in the dark in a saturated
solution of sodium chloride, and is then, after washing with physio-
logical salt solution, bleached by light. Here the regeneration of the
pigment cannot be the result of vital processes, but must be due to
chemical changes in products formed from the original pigment by the
action of light. No such regeneration takes place in a retina which,
after having been bleached in situ, is removed without the pigmented
epithelium and placed in the dark; and the only probable explanation
of the difference is that in this case the photo-chemical substances
from which visual purple can be formed have been absorbed into the
circulation, and have so escaped.
The inner segments of the cones of certain animals (birds, reptiles,
amphibia, and some fishes) contain globules of various colours, ranging
over almost the whole spectrum, and including, besides, the non-spectral
colour, purple. The globules are composed chiefly of fat with the
pigments (chromophanes, as they have been called) dissolved in it.
The function of these globules is unknown. They cannot be concerned
in colour vision, or, at least, they cannot be essential to it, for in the
human retina they do not exist.
The yellow pigment of the macula lutea does not belong to the layer
of rods and cones ; it only exists in the external molecular layer and the
layers in front of it ; in the fovea centralis it is absent.
Time necessary for Excitation of the Retina by Light — Fusion of
Stimuli. — Whatever the exact nature of retinal excitation may be,
it is called forth by exceedingly slight stimuli. A lightning flash,
although it may last only th of a second, lasts long enough
' 1,000,000
to be seen. A beam of light thrown from a rotating mirror on the
eye stimulates when it only acts for 5 th of a second.- The
8,000,000
minimum stimulus in the form of green light corresponds, as we have
already seen (p. 784), to a quantity of work equivalent to no more
than — « erg — that is, about — rn gramme-millimetre, or — . milli-
io8 io10 £ io7
gramme-millimetre, which is the work done by - th of a
10,000,000
milligramme in falling through a millimetre; and it cannot be doubted
that a portion even of this Lilliputian bombardment is wasted as heat.
So quickly, too, is the stimulus followed by the response that no latent
period has as yet ever been measured. It is certain, however, that
there is a latent period, as surely as there is a latent period in the
excitation of a naked nerve-trunk, although this also has never been
experimentally detected. The analogies, in fact, between a muscular
contraction and a retinal excitation are numerous and close. Like the
muscle, the retina seems to possess a store of explosive material which
the stimulus serves only to fire off. The retina, like the muscle, is
exhausted by its activity, and recovers during rest. Like the muscle
curve, the curve of retinal excitation rises not abruptly, but with a
measurable slowness to its height, and when stimulation is stopped,
io5o THE SENSES
takes a sensible time to fall again, the retinal impression outlasting the
luminous stimulus by about one-eighth of a second. With compara-
tively slow intermittent stimuli the retinal, like the muscle curve,
flickers up and down. When the rate of stimulation is increased, the
steady contraction of the tetanized muscle is analogous to the fusion
of the individual stimuli by the tetanized retina (or retino-cerebral
apparatus) into a continuous sensation of light, such, e.g., as the bright
' trail ' of a falling star, or the fiery circle traced in the air when a fire -
brand is rapidly whirled round. But the maximum retinal excitation
which a stimulus of given strength can call forth depends much more
closely upon the time during which the stimulus acts than the maximum
contraction does upon the length of the muscular stimulus.
As the strength of the light increases in geometrical progression, the
time during which it must act in order to produce its maximum effect
decreases approximately in arithmetical progression (Exner) . For light
of moderate intensity this time is about J second. Since for complete
fusion the stimuli must follow each other at a much more rapid rate
than four in the second, the intensity of the resultant sensation is
always less when a succession of similar stimuli are fused than when one
of the stimuli is allowed to produce its maximum effect.
If the time of each stimulus is equal to the interval during which
there is no stimulation, the sensation, when complete fusion has been
reached, is the same as would be produced by a constant light of half
the strength employed. And, in general, if m be the proportion of the
time during which the eye is stimulated by a light of intensity 7, and n
the proportion of the time during which it is not stimulated, the resultant
impression is the same as that which would be produced by an un-
interrupted light of intensity I— — j/. This is Talbot's law, which
may be expressed without the aid of symbols thus: When a light of
given intensity is allowed to act on the eye at intervals so short that the
impressions are completely fused, the resultant
sensation is independent of the absolute length of
each flash, and is proportional only to the fraction
of the whole time which is occupied by flashes and
to the intensity of the light. Talbot's law may be
readily demonstrated by means of a rotating disc
with alternate white and black sectors (Fig.
427), so arranged that the same proportion of the
circumference of each of the three concentric
zones is black.
When the rotation is sufficiently rapid to give
Fig. 446. — Disc for de- complete fusion (say 20 to 30 times a second),
monstrating Talbot's the whole disc appears equally bright. However
law. much the rate of rotation is now increased, no
further change occurs. It has been shown that
even for stimuli as short as the aoo^oftoth of a second, repeated at
intervals of T*gth second, Talbot's law holds good. So that not only
does a flash so inconceivably brief affect the retina, but it sets up
changes which last for a measurable time. For intense stimuli Talbot's
law ceases to be true: the field appears brighter than it should be
(Grunbaum).
Two chief theories have been proposed to account for the fusion of
intermittent retinal stimuli: (i) The persistence theory, according to
which the excitatory process in the retina remains for a short time at
the maximum reached when the light ceases to act. Steady fusion is
supposed to be obtained when the interval between successive stimuli
does not exceed this time. (2) The theory of Fick, who maintains that
VISION 1051
as soon as the light is withdrawn the retinal excitation begins to sink,
at first rapidly, then more gradually. As the rate of stimulation is
increased the time allowed for the decline of the excitation is, of course,
correspondingly shortened, and ultimately the oscillations become so
small that a continuous smooth sensation results. Pick's theory
appears to explain the phenomena best.
The experiments of Charpentier have shown that the retina when
stimulated has a natural tendency to enter-into oscillations at the rate
of about 36 in the second, so that the effect of a flash of light when it
falls on a retinal area is not a single excitation which rises smoothly to
its maximum and then declines smoothly to zero, but a series of swings
which die away like the vibrations of an elastic body. This may be
demonstrated by slowly rotating a well-illuminated disc, one quadrant
of which is white and the rest black, while the eye is kept fixed on the
centre. A black band, or rather sector, running out from centre to
circumference, will be seen in the white quadrant a little behind the
border of it which first passes the eye. This band may be succeeded by
one or more fainter black bands placed at regular intervals in the white
portion of the disc. The explanation is this. At the moment when the
image of the advancing edge of the white quadrant falls upon the
retina it is excited, and we get the sensation of white. Then comes a
swing in the opposite direction which gives rise to the first black band,
and succeeding swings cause the other bands. The period of the oscil-
latory process can be calculated from the speed of the disc, and the
distance of the first band from the edge of the white quadrant. The
well-known fact that a single flash of lightning, or other intense stimulus,
may appear ^s two flashes, finds its explanation in these retinal oscilla-
tions.
Colour Vision. — Besides differences in the distance, size, shape,
and brightness of objects, the eye recognizes differences in their
colour ; and we have now to consider the physical and physiological
differences on which these depend.
Colours may differ from each other — (i) In tone or hue, e.g., red,
yellow, green. (2) In degree of saturation or fulness or purity, i.e., in
the degree in which they are free from admixture with white light, e.g.,
a ' pale ' or ' light ' blue is a blue mixed with much white light, a ' deep '
or ' full ' blue with kttle or none. (3) In brightness or intensity, i.e., in
the amount of the light coming from unit area of the coloured object.
Thus, a ' dark ' red cloth sends comparatively little light to the eye, a
' bright ' red cloth sends a great deal.
When a beam of sunlight falls into the eye, a sensation of ' white
light ' results. When a prism is placed before the eye, the sensation
is entirely different ; we see a spectrum running up from red through
green to violet, with a multitude of intermediate shades, the eye
being able to distinguish in the solar spectrum at least one thousand
different hues (Aubert). What, then, has happened ? Physically,
nothing more has taken place than a rearrangement of the rays
in the beam of white light. A few of them may have been lost by
reflection, but upon the whole the beam is made up of exactly the
same constituents as before; only the rays are now arranged in the
precise order of their refrangibility, the more refrangible, which are
also those of shortest wave-length, being displaced more towards the
base of the prism than the longer and less refrangible rays. In-
1052 THE SENSES
stead of the long and short rays falling together on the same ele-
ments of the retina, as they did in the absence of the prism, they
now fall, if proper precautions have been taken to secure a pure
spectrum, in regular order from one side to the other of the portion
of retina on which the image is formed. The physical condition,
then, of our sensations of the prismatic colours is, that rays of
approximately the same wave-length should fall unmixed with
other rays upon the retinal elements. Rays of a wave-length of
760 fifj,* to 650 IJ.IJL give the sensation of red; from 650 JUJLI to 590 JUJLL,
the sensation of orange; from 430 fijj, to 400 fjLfji, the sensation of
violet, and so on. When rays of all these wave-lengths fall together,
in the proportion in which they are present in sunlight, upon the
same part of the retina, the resultant physiological effect is very
different ; we are no longer able to distinguish red, blue, green, etc. ;
we receive the single sensation of white light. The sensation is a
simple one; in consciousness we have no hint that it has a multiple
physical cause.
But we find further that it is not necessary for the sensation of
white light that waves of every length present in the solar spectrum
should be mixed. If rays of wave-lengths 675 (JLfjL (which acting
alone produce the sensation of red) be mixed in certain proportions
— i.e., be allowed to fall on the same part of the retina — with rays
of wave-length 496 /ufj, (which give the sensation of bluish-green),
the resultant sensation is also that of white light. And an in-
definite number of sets can be combined, two and two, so as to give
the same sensation of white. Such colours are called comple-
mentary. The following are pairs of complementary colours :
Red and bluish-green. Yellow and ultramarine-blue.
Orange and cyan-blue. f Greenish- yellow and violet.
The green of the spectrum has no simple complementary colour;
purple, a colour not present in the spectrum, but obtained by
mixing light from the two spectral extremes — i.e., by mixing red
and violet — may be considered complementary to it. Suppose now
that one of a pair of complementary colours is added to the other
in greater intensity than is required to give white, the resultant
sensation is a colour which has a certain amount of resemblance both
to white and to the colour present in excess. Thus, if the two
colours are orange and blue, and the blue is present in greater in-
tensity than is necessary to give white, the resultant colour is a
whitish or pale blue, or, to use the technical phrase, an unsaturated
blue. The more nearly the intensity of the blue rays in the mixed
light approaches the proportion necessary to give white, the less
saturated is the resultant colour; the greater the excess of blue,
the more nearly does the resultant sensation approach that of the
saturated blue of the spectrum. But any non-saturated spectral
* nn is a symbol representing one-millionth of a millimetre.
| Cyan-blue is a greenish-blue.
VISION 1053
colour produced by the mixture of two complementary colours may
be equally well produced by the mixture of the corresponding
spectral colour with a certain quantity of ordinary white light.
And it is found that when two spectral colours which are not com-
plementary are mixed together the resultant is not white, but a
colour which may be matched by some spectral colour lying between
the two (or by purple), either without addition or plus a larger or
smaller quantity of ordinary white light. From all this it follows
that the retina may be excited by an infinite number of different
physical stimuli, and yet the resultant sensation may be the same.
This leads straight to the conclusion that somewhere or other in
the retino-cerebral apparatus simplification, or synthesis, of im-
pressions must take place ; and we have to inquire what the simplest
assumptions are which will explain all the phenomena. Now, it is
not possible, from two spectral colours alone, to produce a sensation
corresponding to all the others. By mixing three standard spectral
colours, however, in various proportions, we can produce not only
the sensation of white light, but that of every colour of the spectrum
(and of purple). These statements are based on demonstrated facts
obtained by very numerous experiments on colour mixtures. The
hypotheses framed to explain the facts are to be carefully dis-
criminated from the facts themselves.
Primary Colours. — The simplest assumption we can make, then,
is that there are three standard sensations, and that either the
retina itself can respond by no more than three distinct modes of
excitation to the multiplex stimuli of the luminous vibrations, or
that complex impulses set up in the retina are reduced to simplicity
because the central apparatus is capable of responding by only
three distinct kinds of sensation. Which three sensations we select
as fundamental or primary is, to a certain extent, arbitrary, pick
chose red, green, and blue; most commonly red, green, and violet
are accepted as the primary colours. Red, yellow, and blue,
although so long considered the primary colours, from data yielded
by the mixture of pigments, will not do; for no possible combination
of them will produce either a pure green or white light.
The Young-Helmholtz Theory. — The theory which has been most
widely accepted is that of Young, generally called, on account of
its adoption and extension by Helmholtz, the Young-Helmholtz
theory. Red, green, and violet are taken as the fundamental or
elementary colour sensations. In its more modern form it assumes
that in the retina, or in the retino-cerebral apparatus, there are
three kinds of elements — (i) a substance or a component chiefly
affected by light of comparatively long wave-length (red), to a less
extent by light of medium wave-length (green), and to a still less
extent by the shortest visible waves (violet) ; (2) a component mainly
affected by medium, but also to a certain extent by long and short
waves; (3) a component chiefly affected by the short vibrations,
1054
THE SENSES
less by the medium, and still less by the long waves. The curves
in Fig. 44^7 illustrate these relations.
The theory explains as follows the phenomena of colour- mixture
referred to above. When all the rays of the spectrum act upon
the retina together, the three components are about equally affected,
and this equal effect is supposed to be the condition of the sensation
of white light. When the green of the spectrum alone falls on the
retina, the ' green ' component is strongly excited, the other two
Fig. 447. — Curves of Excitability of Primary Sensations from Observations on
Colour Mixtures (Konig). The numbers give wave-lengths of the spectrum in
millionths of a millimetre.
only slightly ; this is the relation between the amount of excitation
in the three components which is associated with a sensation of
spectral green. When two complementary colours, such as red and
bluish-green, fall together on the same portion of the retina, the
three components are excited in the relative proportions associated
with the sensation of white light.
The colour triangle is a graphic method of representing various facts
in colour-mixture (Fig. 44Q).
The chief points to be noted are the following: (i) On the curve
the spectral colours are
arranged at such dis-
tances that the angle con-
tained between straight
lines drawn from the
point marked ' white,'
and intersecting the
curve at the positions
corresponding to any two
colours is proportional to
their difference in tone.
(2) The distance of any
Fig. 448.— Colour Triangle. point of the curve from
the point marked ' white '
is proportional to the stimulation intensity of the colour corresponding
to it. (If the stimulation intensities of all the colours be represented by
VISION 1055
proportional weights lying at the corresponding points on the curve, the
point ' wh ite ' will be the centre of gravity of the system.) (3) The position
of a colour produced by the mixture of any pair of spectral colours is
found by joining the corresponding points by a straight line. The mixed
colour lies on this line at distances from the two points inversely propor-
tional to the stimulation intensity of the two colours — i.e., it lies in the
centre of gravity of the weights representing the two colours. (4) It is a
particular case of (3) that the complementary colours are situated at
the points where straight lines drawn through ' white ' intersect the
curve, since the point marked ' white ' is the centre of gravity corre-
sponding to a pair of colours only when it lies on the straight line
joining them. Thus the orange and yellow lying between the red and
green are mixtures of the red and green sensations in different propor-
tions; the cyan -blue and indigo-blue are mixtures of the green and
violet sensations. The purples, represented by a broken line, are not
present in the spectrum, and are mixtures of red and violet.
It is a point of great theoretical interest that on the Young-Helm-
holtz theory the pure spectral colours, although physically saturated
(i.e., due to ethereal vibrations of a definite wave-length for each
colour), ought not to be physiologically saturated, since they all affect
the three components, although in different degrees. In other words,
the red, let us say, of the spectrum ought not to be the purest or fullest
red which it is possible to perceive. Now, it is found that this is really
the case. If, for example, we look first at the bluish-green, and then
at the red of the spectrum, the sensation of red is fuller or more saturated
than if we had looked at the red directly. Similarly, if we Ipok first at
a small bluish-green square on a black ground, and then at a red ground,
we see a more fully saturated square in the middle of the latter. The
explanation, on the Young-Helmholtz theory, is that the ' green '
component, being fatigued before the eye is turned upon the red, the
latter colour no longer affects it, or affects it less than it would other-
wise do, and therefore the excitation is almost entirely confined to the
red component in the area fatigued for green. This brings us to the
subject of retinal fatigue, and the related phenomena of after-images
and contrast.
After-images. — We have seen that the retinal excitation always takes
time to die away after the stimulus is removed. If a white .object is
looked at, especially when the eye is fresh, for a time not long enough
to cause fatigue, and the eye is then closed, an image of the object
remains for a short time, diminishing in brightness at first rapidly, then
more slowly. This is a positive after-image, and by careful observa-
tion it may, under certain conditions, be seen that the positive after-
image of a white object, of a slit illuminated by sunlight, for example,
undergoes changes of colour as it fades, passing through greenish-blue,
indigo, violet, or rose, to dirty orange. On the Young-Helmholtz
theory this is explained by the supposition that the excitation does
not decline with the same rapidity in the three hypothetical components.
If the object is looked at for a longer time, or if the eye is fatigued, a
dark or negative image may be seen upon the faintly-illuminated ground
of the closed eyes; but negative after-images may be more easily
obtained when the eye, after being made to fix a small white object on
a black ground, is suddenly turned upon a white or neutral tint surface.
Here Helmholtz supposed the portion of the retina on which the
image of the object is formed to be more or less fatigued. And this
fatigue will extend to all three kinds of fibres; so that white light of a
given intensity will now cause less excitation in this part than in the
rest of the retina. It is easy to understand that the negative after-
image of a coloured object will be seen, upon a white ground, in the
1056 THE SENSES
complementary colour, for the components chiefly excited by the latter
will have been least fatigued. The negative after-images seen when
the eye, after receiving the positive impression, is turned upon a coloured
ground, vary with the colour of the object and ground in a manner which
has been explained as due to fatigue of one or other component. It
is difficult, however, to reconcile the fatigue hypothesis of the after-
image with all the facts. Hering supposes that the retina is not
passively fatigued, but that a metabolic change is set up in it which is
of the opposite kind to that caused by the original excitation (see
p. 1057).
The phenomena of negative after-images are often included together
as examples of successive contrast, the name implying mutual in-
fluences of the portions of the retina (or retino-cerebral apparatus)
successively stimulated. We have now to consider simultaneous
contrast, often spoken of simply as contrast.
Contrast.— A small white disc in a black field appears whiter, and a
small black disc in a white field darker, than a large surface of exactly
the same objective brightness. A disc with alternate sectors of white
and black, so arranged that the proportion of white to black increases
in each zone from centre to circumference, when set in rotation, ought,
by Talbot's law, to show sharply marked and uniform rings, of which
each is brighter than that internal to it. But each zone appears
brightest at its inner edge, where it borders on a zone darker than itself,
and darkest at its outer edge, where it borders on a brighter zone. A
plausible explanation of this is based on the assumption that in the
neighbourhood of an excited area of the retina, as well as within the
area itself, the excitability is diminished ; and the same explanation has
been extended to the contrast phenomena of coloured objects. A small
piece of grey paper, e.g., is placed on a green sheet. The grey patch
appears in the complementary colour of the ground — viz., pink or
rose-red (Meyer). The red colour is much stronger if the whole is
covered with translucent tracing-paper. Here we may suppose that
the fatigue of the substance or component chiefly affected by the ground
colour spreads into the portion of the retina occupied by the image oi
the grey paper; the white light coming from the latter, therefore,
affects mainly the component connected with the sensation of the com-
plementary colour.
The curious phenomenon of coloured shadows is also an illustration
of contrast. They may be produced in various ways. For example,
when a lamp is lit hi a room in the twilight, before it has yet grown
too dark, the shadows cast by opaque objects on a white window-blind
are coloured blue. The yellow light of the lamp overpowers the feeble
daylight which passes through the blind, and the general ground is
yeflowish ; but wherever a shadow is thrown it appears of a bluish tint
hi contrast to the yellow ground. Here the only illumination the eye
receives from the region occupied by the shadow is the feeble daylight.
Falling upon an area in which the component chiefly affected by yellow
rays is more or less fatigued, it causes a sensation of the complementary
colour. As darkness conies on, the shadows become black, for now
practically no light at all comes from them.
Helmholtz looked upon simultaneous contrast as a result of false
judgment, and not of a change of excitability in parts of the retina
bordering on the actually excited parts. For the sake of perspective,
it will be worth while to apply this theory by way of illustrating it, to
the explanation of the case of contrast we have just been considering,
from the other point of view, in Meyer's experiment. Helmholtz 's ex-
planation of this experiment is as follows: When a coloured surface is
VISION 1057
covered with translucent paper, the latter appears as a coloured covering
spread over the field. The mind does not recognize that at the grey
patch there is any breach of continuity in this covering; it is therefore
assumed that the greenish veil extends over this spot too. Now, the
grey seen through the translucent white paper is objectively white — i.e.,
sends to the eye the vibrations which together would give the sensation
of white light. But with a green veil in front of it, this could only
happen if the really grey patch was the colour complementary to green
— that is, rose-red. The mind, therefore, judges falsely that the patch
is red. Hering has severely criticized this theory of Helmholtz as to
false judgments; and the weight of evidence certainly seems to be in
favour of the view that simultaneous, like successive, contrast is due
to the influence of one portion of the retina, or retino-cerebral apparatus,
on another.
Hering's Theory of Colour Vision. — The Young- Helmholtz theory
of colour vision has not met with universal acceptance. The best-
known rival theory is that of Hering, who takes his stand upon the
fact that certain visual sensations (red, yellow, green, blue, white,
black) do appear to us to be fundamentally distinct from each other,
while all the rest are obviously mixtures of these. Accepting these
six as primary sensations, he assumes the existence in the visual
nervous apparatus of substances of three different kinds, which may
be called the black-white, the green-red, and the blue-yellow. Like
all other constituents of the body, these substances are broken down
and built up again — in other words, undergo disassimilation and
assimilation, destructive and constructive metabolism. The sensa-
tions of black, of green, and of blue he supposes to be associated with
the constructive, and the sensations of white, of red, ^and of yellow
with the destructive, processes in the three substances. The black-
white substance is used up under the influence of all the rays of the
spectrum, but in different degrees; the smaller the quantity of light
falling on the retina, the more rapidly is it restored, and the more
intense is the sensation of black. The green-red substance is built
up by green rays, broken down by red. The blue- yellow substance
is destroyed by yellow rays, restored by blue. A prominent dif-
ference between this and the Young- Helmholtz theory, and, so far
as it goes, an advantage, is that Hering's theory attempts to assign
a direct objective cause for the visual sensations of white, black,
and yellow, as well as for red, green, and blue, instead of making
the sensations depend upon the magnitude of the stimulation pro-
cess. When any of the visual substances are consumed at one part
of the retina, they are supposed to be more rapidly built up in the
surrounding parts, and in this way many of the phenomena of
simultaneous ^contrast receive an easy and natural explanation. The
same is true of the simpler phenomena of after-images or successive
contrast. But in applying the theory to the more complicated
phenomena difficulties soon emerge, which, to say the least, are not
less formidable than those connected with the Young- Helmholtz
67
1058
THE SENSES
.
theory. Neith'sf theory, in short, can be considered more than a
partially successful attempt to grapple with a very complex mass of
facts. Each, however, has been fruitful in leading to the discovery
of new facts — a great merit in a scientific hypothesis.
Sensibility of Different Parts of the Retina — Perimetry. — The
perception of colours, like the perception of white light, is not
equally distinct over the whole retina. We have repeatedly had
occasion to refer to the fovea centralis as the region of most distinct
vision; but it would be a mistake to suppose that it is therefore
necessarily more sensitive than the rest of the retina. As a matter
of fact, when the minimum intensity of white light which will cause
an impression at all is determined for each portion of the retina, it
is found that the fovea
centralis requires a some-
what stronger stimulus
than the zone immedi-
ately surrounding it. Ob-
jects only a little brighter
than the general ground
on which they lie — e.g.,
very faint stars — are best
seen when the eye is
directed a little to one
side. This has been attri-
buted to the absence of
visual purple from the
fovea, in accordance with
the theory previously
alluded to that the visual
purple acts as a mechan-
ism which ' adapts ' the
retina for the perception
of light of varying inten-
sity. But, with this ex-
ception, the sensibility of
the retina diminishes steadily from centre to periphery, both for
white and for coloured light.
When the eye is fixed, and the visual field — that is, the whole
space from which light can reach the retina in the given position, or,
what comes to the same thing, the projection of the visual field on
the retina by straight lines passing through the nodal point —
explored by means of a perimeter (Figs. 449, 450), it is found that,
under ordinary conditions, a white object is seen over a wider field
than any coloured object, a blue object over a wider field than a
red, and a red over a wider field than a green object. The exact
shape, as well as size, of the visual field also differs somewhat for
Fig. 449. — Priestley Smith's Perimeter. K, rest
for chin; O, position of eye; Ob, object, white or
coloured, which slides on the graduated arc B ;
f, point fixed by the eye.
1059
different colours. In disease of the retina, or of the visual path
between it and the cortex, or of the visual cortex itself, the abridg-
ment of the field for white and for monochromatic light as mapped
out by observations with the perimeter is often of value in diagnosis.
Although it has been shown by Aubert and others that monochro-
matic light of considerable intensity can be perceived over the whole
retina, yet it may be said that the retinal rim is even then relatively
and, under ordinary conditions, absolutely colour-blind. This and
XI
vm
TV
Fig. 450. — Perimetric Chart of Right Eye (after Hirschberg). The numbers repre-
sent degrees of the visual field measured on the graduated arc of the perimeter.
w, boundary of field for white object ; b, for blue ; r , for red ; g, for green ; m, blind
spot; M, medial, and L, lateral side of the field of vision. The Roman numbers
represent twelve meridians of the retina, each making an angle of 30° with
the next. They fix the ' longitude ' of any point in the field. The concentric
circles indicated by Arabic numbers represent angular distances from the
fixation point in the planes of these meridians. They give the ' latitude ' of any
point.
other facts have given rise to thetheory (p. 1047) that the rods, which
are alone present at the ora serrata, are concerned in achromatic
vision (under conditions of dark adaptation), the cones in colour
vision as well as in achromatic vision (under daylight conditions).
This brings us to the subject of colour-blindness, a phenomenon
of great interest in its theoretical as well as in its practical bearings.
Colour-Blindness. — A considerable number of persons (about
4 per cent, of all males, but only one-tenth of this proportion of
1060 THE SENSES
females) are deficient in the power of distinguishing between certain
colours. They are said to be colour-blind ; but the term must not
be taken to signify that they are absolutely devoid of colour-sensa-
tions. A very small minority of the colour-blind appear to have
but one sensation of colour tone, everything appearing as white,
grey, or black (total colour-blindness, sometimes called mono-
chromatic vision) . All colours are confused by them, but differences
of brightness are correctly appreciated. Probably the totally
colour-blind person receives somewhat the same impressions from
a coloured picture as the normal person does from a reproduction
of the same picture in black-and-white. There are close resemblances
between the vision of the totally colour-blind eye and that of the
normal eye adapted by resting in the dark for twilight vision. The
fovea is relatively, and in some cases absolutely, insensitive to
light, while the peripheral portion of the retina is normal, or nearly
normal, in this regard. This is the foundation of the theory that in
total colour-blindness the cones are devoid of their normal func-
tions, and that the hypothetical mechanism for twilight vision (the
rods) is functioning alone. In another condition (night-blindness,
or hemeralopia) it is sometimes assumed that the other mechanism
(that of the cones) which is adapted for daylight vision, and has
little power of dark-adaptation, is alone acting. But it cannot be
said that this has been proved.
The rest of the colour-blind are dichromatic — i.e., their colour
reactions seem to correspond only to two of the fundamental colour
sensations of She normal person and their combinations, in addition
to white. Of the dichromates a very few confuse blue with yellow.
The great majority are unable to distinguish between red and green.
The condition will be most easily understood by considering some
of the extraordinary mistakes which may be made by the colour-
blind, without necessarily leading them to suspect that there is any-
thing abnormal in their vision. Thus, to quote the words of a
distinguished writer on this subject, himself a sufferer from the
deficiency : ' A naval officer purchases red breeches to match his
blue uniform ; a tailor repairs a black article of dress with crimson
cloth; a painter colours trees red, the sky pink, and human cheeks
blue.' The shoemaker, Harris, the discoverer of colour-blindness,
picked up a stocking, and was surprised to hear other people
describe it as a red stocking; it seemed to him only a stocking.
The celebrated Dalton was twenty-six years of age before he knew
that he was colour-blind. He matched samples of red, pink,
orange, and brown silk with green of different shades; blue both
with pink and with violet; lilac with grey.
When the condition of vision in dichromates is tested by means of
the spectrum, it is found that they fall into two classes: (i) A class
(of green-blind) by whom the whole of the spectrum from red to yellow is
described as yellow of different degrees of brightness (intensity) ; the green
ro6i
appears as a pale yellow with a grey or white band in its midst; while
the violet end is seen as different shades of blue. (2) A class of (red-
blind) whose whole spectrum, from red to green, is seen as green of
different intensities, the extreme red being entirely invisible. The
violet end is blue, as in (i), and there is a band of white or grey near
the blue end of the green.
Sir John Herschell explained Dalton's peculiarity of vision on the
hypothesis that he only possessed two, instead of three, primary
sensations.
On the Young-Helmholtz theory, the missing sensation is supposed
to be either red or green. At the intersection of the curves that repre-
sent the violet and green sensations (Fig. 447), the red-blind individual
will see what he describes as white — viz., the sensation produced by
the stimulation of the only two components he possesses. Similarly,
at the intersection of the red and violet curves the green-blind person
will see what is white to him.
Those who have attempted to explain colour-blindness on Hering's
theory have usually assumed that the colour-blind possess the blue-
yellow, but lack the green-red visual substance. So that on this theory
there should be no difference between red-blindness and green-blind-
ness. But v. Kries, in a study of twenty cases of congenital partial
colour-blindness, brings forward strong evidence that the red-green
blind can be divided, as regards the comparison of red (lithium) and
orange (sodium) light, into two sharply-separated groups — a result
which is, so far as it goes, in favour of the Young-Helmholtz theory,
and against the theory of Hering.
The observations of Burch on temporary colour-blindness produced
by placing the eye behind a transparent coloured screen and focussing
a beam of strong sunlight on it, lend additional support to the former
theory. Thus, if a spectrum is looked at after green-blindness has been
induced by exposure of the eye to green light, the red portion of the
spectrum seems to pass into the blue, and no intermediate green band
is seen. If the eye is exposed to yellow light it becomes temporarily
blind not only for yellow, but also for red and green. This is in favour
of the assumption of the Young-Helmholtz theory that the sensation
of yellow is caused when the retinal elements concerned in the production
of the sensations of red and green are simultaneously stimulated. It is,
however, equally difficult to reconcile some of the phenomena of colour-
blindness with the Young-Helmholtz theory. Anomalies and defects
of colour-sensation are common accompaniments of pathological lesions
of the visual apparatus, and can be produced by various drugs, as by
abuse of tobacco. But colour-blindness, in its true sense, is con-
genital, often hereditary; the colour-blind are ' born, not made.' And
although the condition cannot be cured, it is of great importance that
it should be recognized in the case of persons occupying positions such
as those of engine-drivers, railway-guards, and sailors, in which coloured
lights have to be distinguished. For, while it is true that the sensations
which red and green lights give the colour-blind are far from being
identical (Pole) under favourable conditions, it is precisely when the
conditions are unfavourable— as in a fog or a snow-storm — that the
capacity of distinguishing them becomes invaluable (Practical Ex-
ercises, p. 1112).
Irradiation. — The phenomenon known as irradiation was first
described by Kepler, who gave as an example the appearance known
as the 'new moon in the old moon's arms/ where the crescent of the
new moon seems to overlap and embrace the unilluminated portion of the
lunar disc. A white circle on a black ground (Fig. 451) appears, in
I062 THE SENSES
a good light, to be larger than an exactly equal black circle on a white
ground. The explanation is as follows: Owing to the aberration of the
refractive media of the eye (p. 1027), all the rays proceeding from, the
luminous object are not brought accurately to a focus on the retina,
and the image is surrounded by diffusion circles (p. 1028) which encroach
upon the unilluminated boundary. Physically these represent a
weaker illumination than that of the image proper, and therefore the
latter ought to stand out in its real size as a brighter area surrounded by
weaker haloes. That this is not the case, and that the image is pro-
jected in its full brightness for a certain distance over its dark boundary,
is due to the fact that the eye does not recognize very small differences
of brightness. When the accommodation is not perfect, the diffusion
circles are, of course, much wider, and irradiation is better marked when
the object is a little out of focus.
The Movements of the Eyes. — That the eyes may be efficient
instruments of vision, it is necessary that they should have the
power of moving independently of the head. An eye which could
not move, thoiigh certainly better than an eye which could not see,
would yet be as imperfect after
its kind as a ship which could
run before the wind, but could
not tack. The mere fact that
the angle between the visual
axes must be adapted to the
distance of the object looked at
p. renders this obvious; and the
beauty of the intrinsic mechan-
ism of the eyeball has its fitting complement in the precision,
delicacy, and range of movement conferred upon it by its extrinsic
muscles.
Not only are movements of convergence and divergence of the
eyeballs necessary in accommodating for objects at different dis-
tances, but without compensatory movements of the eyes it would
be impossible to avoid diplopiawith every movement of the head;
for the images of an object fixed in one position of the head would
not continue to fall on corresponding points of the retinae in another
position.
All the complicated movements of the eyeball may be looked
upon as rotations round axes passing through a single point, which
to a near approximation always remains fixed, and is situated about
1 77 mm. behind the centre of the eye.
The position which the eyeballs take up when the gaze is directed to
the horizon, or to any distant point at the level of the eyes, is called
the primary position. Here the visual axes are parallel, and the plane
passing through them horizontal. While the head remains fixed in this
position, the eyeballs can rotate up or down around a horizontal axis,
or from side to side around a vertical axis; or upwards and inwaids,
downwards and outwards, downwards and inwards, and upwards and
outwards around oblique axes, which always lie in the same plane as
the vertical and horizontal axes of rotation — i.e., in the vertical plane
VISION
1063
passing through the fixed centre of rotation. These facts, spoken of
collectively as Listing's law, and first deduced by him from theoretical
considerations, were afterwards proved experimentally by Helmholtz
and Bonders. It necessarily follows from Listing's law (and this is,
indeed, another way of stating it) that in moving from the primary posi-
tion into any other, there is no rotation of the eyeball round the visual
axis — no wheel-movement, as it is called.
A true rotation of the eye round the visual axis does, however, occur
when the eyes are converged as in accommodation for a near object,
each eyeball rotating towards the temporal side. This is especially the
case when the eyes are at the same time converged and directed down-
wards; and the rotation may amount to as much as 5°. When the
head is rolled from side to side, while the eyes are kept fixed on an
object, a slight compensatory rotation of the eyeballs takes place
against the direction of rotation of the head. The amount of rotation
of the eyes is relatively greater for small than for large movements of
the head (eye 5° for head 20°; eye 10° for head 80° — Kiister).
The Extrinsic Muscles of the Eyes. — The eyeball is acted upon by
six muscles arranged in three pairs, which may be considered,
roughly speaking, as antagonistic sets. These are the internal and
external recti, the superior and
inferior recti, and the superior ^ -—I — ^ . ^Obl SM
and inferior obliqui.
'Although the movements of the
eye have been very fully studied,
and are, upon the whole, well
understood, our knowledge of the
manner in which any given move-
ment is brought about, and of the
exact action of the muscles which
take part in it, is by no means
as copious and precise. From
the nature of the case, the greater
part of what we do know has
been inferred from the anatomical
relations of the muscles as re-
vealed by dissection in the dead
'Hint
sap
R ext B inf
Fig. 452. — Horizontal Section of Left
Eye. Arrows show direction of
pull of the muscles. The axis of
rotation of the external and internal
recti would pass through the inter-
section of a and /3 at right angles
to the plane of the paper.
body rather than gained from actual observation of the living eye.
A plane, called the plane of traction, is supposed to pass through the
middle points of the origin and insertion of the muscle whose action
is to be investigated, and through the centre of rotation of the
eyeball. A straight line drawn at right angles to this plane through
the centre of rotation is evidently the axis round which the muscle
when it contracts will cause the eye to rotate, provided that the
fibres of the muscle are symmetrically distributed on each side of
the plane of traction. The axes of rotation of the antagonistic
pairs almost, but not completely, coincide with each other. The
common axis of the external and internal recti practically coincides
with the vertical axis of the eyeball (Fig. 452) in the primary posi-
io64 THE SENSES
tion. The eye is turned towards the temple when the external
rectus alone contracts, towards the nose when the internal rectus
alone contracts. The common axis of the superior and inferior
recti, (3, lies in the horizontal visual plane in the primary position,
but makes an angle of about 20° with the transverse axis, its inner
end being tilted forwards. The consequence is that contraction
of the superior rectus turns the eye up, and contraction of the
inferior rectus turns it down, but both movements are also com-
bined with a slight inward rotation. The common axis of the
oblique muscles, a, makes an angle of 60° with the transverse axis,
the outer end of it being the most anterior. The direction of traction
of the superior oblique is, of course, given not by the line joining
its bony origin and its insertion, but by the direction of the portion
reflected over the pulley. When the superior oblique contracts
alone, the eyeball is rotated outwards and downwards ; the inferior
oblique causes an outward and upward rotation. None of the
common axes of rotation of the pairs of muscles, except that of the
external and internal recti, lies in Listing's plane. Now, as we have
seen that every movement which the eye, supposed to be originally
in the primary position, can execute may be considered as a rota-
tion round an axis in this plane, it is clear that every movement,
except truly transverse rotation, must be brought about by more
than one pair of muscles. For vertical rotation, the inward pull of
the superior rectus is antagonized by a simultaneous outward pull
of the inferior oblique ; for downward rotation, the inferior rectus
and superior oblique act together. In oblique movements, a muscle
of each of the three pairs is concerned. The effect on the eyeball
of simultaneous contraction of certain pairs of muscles may be
summarized thus:
External rectus (outward) + internal rectus (in ward) = none.
Superior rectus (upward and inward) + inferior oblique (upward and
outward) = upward.
Inferior rectus (downward and inward) + superior oblique (downward
and out ward)= downward.
SECTION II. — HEARING.
The transverse vibrations of the ether fall upon all parts of the surface
of the body, but only find nerve-endings capable of giving the sensa-
tion of light in the little discs, which we call the retinae. So the much
longer and slower longitudinal waves of condensation and rarefaction
which are being constantly originated in the air or imparted to it by
solid or liquid bodies that have been themselves set vibrating fall upon
all parts of the surface, but only produce the sensation of sound when
they strike upon the tiny mechanism of the internal ear.
But just as the ethereal vibrations, and especially those of greater
wave-length, are able to excite certain end-organs in the skin which
have to do with the sensation of temperature, so the sound-waves,
when sufficiently large, are also capable of stimulating certain cutaneous
HEARING
1065
nerves and of giving rise to a sensation of intermittent pressure or thrill.
This is readily perceived when the finger is immersed in a vessel of
water into which dips a tube connected with a source of sound, or when
a vibrating bell or tuning-fork is touched. So far as we know, what
takes place in the ear is essentially similar — that is to say, a mechanical
stimulation of the ends of the auditory nerve, but a stimulation which
acts through, and is graduated and controlled by, a special intermediate
mechanism.
As the visual apparatus consists of a sensitive surface, the retina,
which contains the end-organs of the optic nerve and of dioptric
arrangements which receive and focus the rays of light, the auditory
apparatus consists of the sensitive end-organs of the cochlear divi-
sion of the eighth nerve and of a mechanism which receives the
sound-waves and communicates them to these.
Physiological Anatomy of the Ear. — At the bottom of the external
auditory meatus lies the membrana tympani, a nearly circular mem-
brane set like a drum-skin in a
ring of bone, and separating the
meatus from the tympanum or
middle ear. Its external surface
looks obliquely downwards, and
at the same time somewhat for-
wards, so that if prolonged the
membranes of the two ears would
cut each other in front of, and also
below, the horizontal line passing
through the centre of each (Figs.
453.454)-" ,
The tympanum contains a
chain of little bones stretching
right across it from outer to inner
wall. Of these the malleus, or
hammer, is the most external.
Its manubrium, or handle, is in-
serted into the membrana tym-
pani, which is not stretched taut
within its bony ring, but bulges
in wards .at the centre, where the
handle of the malleus isattached.
The stapes, or stirrup, is the most
internal of the chain of ossicles,
and is inserted by its foot-plate
into a small oval opening — the
foramen ovale — on the inner wall of the tympanic cavity. A mem-
branous ring — the orbicular membrane — surrounds the foot of the
stapes, helping to fill up the foramen and attaching the bone to its
edges. The inner surface of the foot of the stapes is in contact with
the perilymph of the internal ear. The incus, or anvil, forms a link
between the malleus and the stapes. The auditory ossicles, as well as
the whole cavity of the tympanum, are covered by pavement epithelium.
The tympanum is not an absolutely closed chamber; it has one
channel of communication with the external air — the Eustachian tube
which opens into the pharynx. By the action of the cilia lining this
tube the scanty secretion of the middle ear is moved towards its
pharyngeal opening, which, usually closed, is opened when a swallowing
Fig. 453.^The Ear. m, external meatus;
/, head of malleus; o, short process of
malleus; g, handle of malleus; h, incus;
i, foot of stapes in oval foramen; e, tym-
panic membrane.
io66
THE SENSES
movement occurs. Its function is to keep the pressure in the middle
ear approximately that oj the atmosphere. ~in a pauooiT ascent an
excess of pressure is established on the internal surface of the tympanic
membrane. In the air-lock of a caisson when the air is being com-
pressed the excess of pressure is on the external surface of the membrane.
The feeling of uncomfortable tension is relieved in both cases by swallow-
ing movements which allow the pressure in the tympanum to adjust
itself to that in the pharynx. In catarrh of the naso-pharynx the
orifice may be occluded, and this is accompanied by impairment of
hearing and a disagreeable sensation of tension in the ear, owing to
absorption and consequent rarefaction of the air in the tympanum.
The patient instinc-
tively makes efforts
which increase the pha-
ryngeal pressure from
time to time so as to
open the tube.
The loosely - jointed
chain of ossicles is
steadied and its move-
ments directed by liga-
ments and by the ten-
sion of its terminal mem-
branes. It forms a kind
of bent lever by which
the oscillations of the
membrana tympani are
transferred to the mem-
brane covering the oval
foramen, and at the
same time reduced in
size. Two slender
muscles, the tensor tym-
pani and stapedius, con-
tained in the tympanic
cavity, are also con-
nected with and may
act upon the ossicles.
The former lies in a
groove above the Eusta-
chian tube, and its
tendon, passing round a
kind of osseous pulley
(processus cochleari-
formis), is inserted into the handle of the malleus; the stapedius is
lodged in a hollow of the inner bony wall of the tympanum. Its
tendon is attached to the neck of the stapes near its articulation with
the incus. This inner wall is pierced not only by the oval foramen,
but also by a round opening, the fenestra rotunda, which is closed by
a membrane to which the name of secondary membrana tympani is
sometimes given.
The internal ear consists of the bony labyrinth, a series of curiously
excavated and communicating spaces in the substance of the petrous
portion of the temporal bone, filled with a liquid called the perilymph,
in which, anchored by strands of connective tissue, floats a correspond-
ing series of membranous canals (the membranous labyrinth), filled
with a liquid called endolymph. The labyrinth of the internal ear is
Fig- 454- — Tympanum of Left Ear, showing the
Ossicles (Morris), i, superior, and 4, external,
ligament of malleus; 2, head; 7, short process, and
10, manubrium or handle, of malleus; 5, longprocess
of incus, terminating in 9, the os orbiculare; 6, base,
and 8, head, of stapes; n, Eustachian tube; 12, ex-
ternal auditory meatus; 13, membrana tympani;
3, upper, and 14, lower, part of tympanum.
1067
divided into three well-marked parts: the cochlea, the vestibule, and
the semicircular canals (Fig. 455). The cochlea, the most anterior of
the three, consists of a convoluted tube which coils round a central
pillar, the columella or modiolus, like a spiral staircase. The lamina
spiralis projects from the modiolus and divides the tube into an upper
compartment, the scala vestibuli, and a lower, the scala tympani
(Fig. 456). The part of the lamina next the modiolus is of bone, but it
is completed at its outer edge by a membrane, the lamina spiralis mem-
branacea, or basilar membrane. The scala tympani abuts on the
fenestra rotunda, and its perilymph is only separated from the air of
the tympanic cavity by the membrane which closes that opening.
At the apex of the cochlea the lamina spiralis is incomplete, ending In
a crescentic border, so that the scala tympani and the scala vestibuli
here communicate by a small opening, the helicotrema. The scala
vestibuli communicates with the vestibule, and the vestibule with the
semicircular canals, so that the perilymph of the entire labyrinth forms
a continuous sheet separated from the cavity of the middle ear by the
2-...
Fig. 455. — Diagram of Right Membranous Labyrinth (after lestut). I, utricle;
2, 3, 4, superior, posterior, and horizontal semicircular canals; 5, saccule;
6, ductus endolymphaticus arising by two branches, 7, 7'; 8; saccus endo-
lymphaticus; 9, canalis cochlearis (canal of the cochlea) ending at 9', and 9*;
10, canalis reunions.
structures that fill up the round and oval foramina. In the mem-
branous labyrinth, and in it alone, are contained the end-organs of the
auditory nerve. The membranous portion of the cochlea is a small
canal of triangular section, cut off from the scala vestibuli by the mem-
brane of Reissner, which stretches from near the edge of the bony
spiral lamina to the outer wall (Fig. 457), to which it is attached by the
spiral ligament. The canal has received the name of the scala media,
or canal of the cochlea. The membrane of Reissner forms its roof.
Its floor is composed (i) of the projecting edge of the spiral lamina,
called the limbus, and (z) of the basilar membrane. The most con-
spicuous constituent of the basilar membrane is a layer of stiff, parallel,
transparent fibres arranged radially — i.e., in the direction from limbus
to spiral ligament. They are embedded in a homogeneous material.
Below the cochlear canal ends blindly, but communicates by a side-
channel with the portion of the membranous vestibule called the sac-
cule, which in its turn communicates with the utricle by the Y-shaped
origin of the ductus endolymphaticus. Into the utricle open the three
io68
THE SENSES
semicircular canals, the endolymph of which has, therefore, free com-
munication with that of the vestibule and cochlea. But although the
semicircular canals and vestibule belong anatomically to the internal
ear, and are supplied by branches of the auditory nerve, we have no
positive proof that in the higher animals, at least, they are in any way
concerned in hearing; and since experiment has assigned them a
definite function of another kind (p. 936), we shall not consider them
str.v.
Fig. 456. — Longitudinal Section through the Cochlea of a Cat (Schafer, after Sobotta)
X 25 . dc, canal or duct of cochlea ; scv, scala vestibuli ; set , scala tympani ; w, bony
wall of cochlea; C, organ of Corti ; mR, Reissner's membrane ; n, fibres of cochlear
nerve; gsp, ganglion spirale; str.v., stria vascularis.
further in this connection. The seala media contains the organ of Corti,
which (Fig. 458) consists of a series of modified epithelial cells planted
upon the basilar membrane. The epithelial cells are of three kinds:
(i) supporting epithelial cells; (2) the pillars or rods of Corti, in two
series (inner and outer), sloped against each other like the rafters of a
roof, and covering in a vault or tunnel which runs along the whole of
the scala media from the base to the apex of the cochlea; (3) the hair-
cells, around which the fibres of the auditory nerve arborize. These
last are columnar epithelial cells, surmounted by hairs. They are
HEARING
1069
arranged in several rows, one row lying just internal to the inner line
of pillars, and several rows external to the outer line of pillars. Be-
tween the outer hair-cells are supporting cells (cells of Deiters). A thin
membrane, the reticular lamina or membrana reticularis, composed of
fiddle-shaped rings or phalanges, covers the hair-cells, and through
openings in it the hairs project. A thicker membrane, the membrana
tectoria, springing from the edge of the osseous spiral lamina near the
attachment of Reissner's membrane, forms a kind of canopy over both
pillars and hair-cells. The outer wall of the canal of the cochlea is
clad by cubical epithelium covering a membrane richly supplied with
bloodvessels (stria vascularis). The fact that the hair-cells of Corti's
organ are connected with the fibres of the cochlear division of the
Fig. 457. — Vertical Section of the First Turn of the Cochlea (after Retzius). D.C.
canal of cochlea; tC, tunnel of Corti; b.m, basilar membrane; h.i, h.e, internal
and external hair-cells; Mt, membrana tectoria; s.sp, spiral groove; str.v, stria
vascularis; sp.l, spiral lamina; n, fibres of the cochlear nerve; /, limbus laminae
spiralis; R, Reissner's membrane; s.v, scala vestibuli; s.t, scala tympani; l.sp,
spiral ligament.
auditory nerve, and its elaborate structure, suggest that it must play
a peculiar part in auditory sensation. Comparative anatomy shows
us that the cochlea is the most highly developed portion of the internal
ear, the last to appear in its evolution, and the most specialized. It
is absent in fishes, which possess only a vestibule and one to three semi-
circular canals. It first acquires importance in reptiles, but attains
its highest development in mammals; and there is every reason to
believe that it is the terminal apparatus of the sense of hearing.
Functions of the Auditory Ossicles. — -The anatomical arrange
ments of the middle ear suggest that the tympanic membrane and
the chain of ossicles have the function of transmitting the sound-
waves to the liquids of the labyrinth; and observation and experi-
THE SENSES
ment fully confirm this idea. Tracings of the movements of the
ossicles have been obtained by attaching very small levers to them,
and their movements have been directly observed with the micro-
scope. Even in man it may be shown, by viewing the membrane
through a series of slits in a rapidly-revolving disc (stroboscope),
that it vibrates when sound-waves fall on it.
When the handle of the malleus moves inwards, rotating around
an axis which may be supposed to pass through its neck, its head
moves in the opposite direction. The joint between that bone and
the incus is thus locked, on account of the shape of the articular
surfaces. The long process of the incus, constituting the second
n
mb
Fig. 458. — Organ of Corti (Barker, after Retzius). mb, basilar membrane; tb, its
tympanal covering; vs, bloodvessel (vas spirale); re, medullated distal processes
of bipolar nerve-cells in the ganglion spirale, passing in to arborize around the
hair -cells; tS, epithelial cells continuous with the epithelium of the sulcus
spiralis internus; p, inner pillar of Corti, with its basal cell, b ; p', outer pillar
with its basal cell, b' ; i, 2, 3, supporting cells of Deiters, whose processes run up
to be attached to the lamina reticularis, r ; H, Hensen's supporting cells; C, cells
of Claudius ; i, internal hair-cell with its hairs, »' (the upper part of the hair -cell
is concealed by the head of the inner pillar of Corti) ; e, external hair-cell; e', hairs
of three external hair -cells; n, n1, to n*, cross-sections of the spiral strand of
cochlear nerve-fibres.
portion of the bent lever, passes inwards, carrying with it the stapes,
which is attached to it by an almost rigid joint, and the stapes is
pressed into the oval foramen. Since the long process of the incus
is about one-third shorter than the handle of the malleus, the ex-
cursion of the point of the former is correspondingly smaller than
that of the latter, but at the same time more powerful. When the
tympanic membrane passes outwards, the handle of the malleus
and foot of the stapes do the same. But the joint now unlocks, and
excessive outward movement of the stapes, which might result in
its being torn from its orbicular attachment, is prevented. The
ossicles vibrate en masse. It is only to a trifling extent that sound
HEARING 1071
can be conducted through them to the labyrinth as a molecular
vibration; for when they are anchylosed, and the foot of the stapes
fixed immovably in the foramen ovale, as sometimes occurs in
disease, hearing is greatly impaired.
Of course, every vibration of the tympanic membrane must cause
a corresponding condensation and rarefaction of the air in the
middle ear; and this may act on the membrane closing the fenestra
rotunda, and set up oscillations in the perilymph of the scala tym-
pani. That this is a possible method of conduction of sound is
shown by the fact that, even after closure of the oval foramen, a
slight power of hearing may remain. But under ordinary con-
ditions by far the most important part of the conduction takes
place via the ossicles. And when it is remembered that the tym-
panic membrane is about thirty times larger than that which fills
the oval foramen, it will be seen that the force acting on unit area
of the foot of the stapes may be much greater than that acting on
unit area of the membrana tympani, and that the mode of trans-
mission by the ossicles is a very advantageous method of trans-
forming the feeble but comparatively large excursions of the tym-
panic membrane into the smaller but more powerful movements of
the stapes. The average excursion of the membrane of the oval
foramen does not at most amount to more than 0-04 millimetre. -.
Even the so-called cranial conduction of sound when a tuning-fork /
is held between the teeth or put in contact with the head, which
was at* one time supposed to be due solely to direct transmission
of the vibrations through the bones of the skull to the liquids of
the labyrinth or the end-organs of the auditory nerve, has been
shown to take place, in great part, through the membrana tympani
and ossicles; the vibrations travel through the bones to the tym-
panic membrane, and set it oscillating. So that this test, when
applied to distinguish deafness caused by disease of the middle ear
from deafness due to disease of the labyrinth or the central nervous
system, may easily mislead, although it enables us to say whether
the auditory meatus is blocked — by wax, e.g. — beyond the tym-
panic membrane.
A membrane like a drum-head has a note of its own, which it gives
out when struck, and it vibrates more readily to this note than to any
other. It would evidently be a serious disadvantage if the tympanic
membrane, whose office it is to receive all kinds of vibrations, and
respond to all, had a marked fundamental tone which would be con-
tinually obtruding itself among other notes. The difficulty is obviated
by the damping action of the ossicles and the liquids of the labyrinth
on the movements of the membrane, which in addition is not stretched,
but lies slackly in its bony frame, so that when the handle of the malleus
is detached from it, it retains its shape and position.
The tensor tympani, when it contracts, pulls inwards the handle of
the malleus, and thus increases the tension of the tympanic membrane.
The precise object of this is obscure. It has been suggested that damp-
1072 THE SENSES
ing of the movements of the auditory ossicles is thus secured. Another
theory is that the increased tension of the membrane renders it more
capable of responding to higher tones, and that the muscle thus acts as
a kind of accommodating mechanism. But Hensen has observed that
the tensor only contracts at the beginning of a sound, and relaxes again
when the sound is continued ; and this is difficult to reconcile with either
of these hypotheses. The muscle is normally excited reflexly through
the vibrations of the membrana tympani, but some individuals have
the power of throwing it into voluntary contraction, which is accom-
panied by a feeling of pressure in the ear, and a harsh sound. The
function of the stapedius is unknown. Its contraction would tend to
press the posterior end of the foot-plate of the stapes deeper into the
foramen ovale, and cause the anterior end to move in the opposite
direction ; but it is not easy to see how this would affect the action of
the auditory mechanism.
The tensor tympani is supplied by the fifth nerve through a branch
from the otic ganglion; the stapedius is supplied by the seventh.
Paralysis of the fifth nerve may be accompanied with difficulty of
hearing, especially for faint sounds. When the seventh nerve is
paralyzed, increased sensitiveness to loud sounds has been observed.
We have already recognized the organ of Corti, particularly the
hair-cells, as a sensory epithelium which constitutes the terminal
apparatus of the cochlear nerve. The adequate stimulus of the
auditory receptors is the periodic changes of pressure in the endo-
lymph. But there are various opinions as to how these vibrations
are transmitted to the hair-cells, and as to how the vibrations of
the hair-cells are translated into nerve impulses in the auditory
fibres. The pillars of Corti, the basilar membrane, and the mem-
brana tectoria, have in turn been regarded as the structures im-
mediately set into vibration by the changes in the endolymph.
The case for the tectorial membrane is perhaps the most plausible,
for its position renders it most capable of acting on the hairs.
Others have supposed that the hairs of the hair-cells are directly
affected by the endolymph. Some, despairing of further analysis,
content themselves with the conclusion that the organ of Corti
vibrates as a whole. Some of these theories will be again referred
to in considering what is the greatest problem of the physiology of
hearing, viz. :
The Perception of Pitch — Analysis of Complex Sounds. — As the
eye, or, rather, the retina plus the brain, can perceive colour, so the
labyrinth plus the brain can perceive pitch. The colour-sensation
produced by ethereal waves of definite frequency depends on that
frequency ; and upon the frequency of the aerial vibrations depends
also the pitch of a musical note. But there is this difference be-
tween the eye and the ear : that while the sensation produced by a
mixture of rays of light of different wave-length is always a simple
sensation — that is, a sensation which we do not perceive to be built
up of a number of sensations, which, in other words, we do not
analyze — the ear can perceive at the same time, and distinguish
HEARING 1073
from each other, the components of a complex sound. When a
number of notes of different pitch are sounded together at the
same distance from the ear the disturbance which reaches the mem-
brana tympani is the physical resultant of all the disturbances pro-
duced by the individual notes, and it strikes upon the membrane as
a single wave. ' A single curve describes all that the ear can possibly
hear as the result of the most complicated musical performance.
... In the complicated sound the variations of the pressure of the
air are more abrupt, more sudden, less smooth, and less distinctly
periodic than they are in softer, purer, and simpler sound. But the
superposition of the different effects is really a marvel of marvels '
(Kelvin). The ear or brain must, therefore, possess the power of
resolving the complex vibrations into their constituents, else we
should have a mixed or blended sensation, and not a sensation in
which it is possible to distinguish the constituents of which it is
made up. Several hypotheses have been proposed to explain this
physiological analysis of sound, on the assumption that the analysis
takes place in the labyrinth. The most important, in spite of certain
defects, is still that of Helmholtz.
Helmholtz attempted to explain the perception of pitch on the
assumption that in the internal ear there exists a series of resonators,
each of which is fitted to respond by sympathetic vibration to a
particular note, while the others are unaffected; just as when a note
is sung before an open piano it is taken up by the string which is
attuned to the same pitch and ignored by the rest. Let us sup-
pose that a given fibre of the auditory nerve ends in an organ which
is only set vibrating by waves impinging on it at the rate of 100 a
second, and that the end-organ of another fibre is only influenced
by waves with a frequency of 200 a second. Then, on the doctrine
of ' specific energy ' (according to which the sensation caused by
stimulation of a nerve depends not on the particular kind of stimu-
lus but on the anatomical connection of the nerve with certain
nerve centres), in whatever way the first fibre is excited, a sensation
corresponding to a note with a pitch of 100 a second will be per-
ceived. Whenever the second fibre is excited, the sensation will be
that of a note of 200 a second, or the octave of the first. If both
fibres are excited at the same time the two notes will be heard
together. Now, Hensen actually observed that in the auditory
organs of some crustaceans, the hair-like processes of certain
epithelial cells can be set swinging by waves of sound, and, further,
that they do not all vibrate to the same note unless the sound is
very loud. In the lobster there are between four and five hundred
of these hairs, varying in length from 14 ft to 740 /JL ; and in some
insects, such as the locust, similar hairs, also graduated in length,
exist.
To gain an anatomical basis for his theory, Helmholtz supposed
first of all that the pillars of Corti were the vibrating structures,
68
1074 THE SENSES
and that, directly or through the hair-cells, their mechanical vibra-
tions were translated into impulses in the auditory nerve-fibres.
But apart from the fact that their number is too small (about 3,000)
to allow us to assign one rod to each perceptible difference of pitch,
and their dimensions too similar to permit of the requisite range
of vibration frequency, it was pointed out that birds do not possess
pillars of Corti — a fact which was decisive against the assumption
of Helmholtz, since nobody denies to singing-birds the power of
appreciating pitch. Helmholtz accordingly, choosing between the
remaining possibilities, gave up the pillars of Corti, and adopting
a suggestion of Hensen, substituted the radial fibres of the basilar
membrane as his hypothetical resonators. These are more ade-
quate to the task imposed on them, since their range of length is
far greater (41 fjL at the base to 495 fj, at the apex of the cochlea —
Hensen); and the elaborate structure of Corti 's organ certainly
suggests that some one or other of its elements may be endowed
with such a function. Experimentally, too, it has been shown
that destruction of the apex of the cochlea causes loss of appreciation
of low notes, and destruction of the base loss of appreciation of high
notes, which agrees with Helmholtz's view. But while the theory
of peripheral analysis of pitch tends upon the whole to be strength-
ened as evidence gathers, it is possible that the analysis is accom-
plished in some other way than by sympathetic resonance.
Ewald has developed a theory according to which each note causes
the basilar membrane to vibrate throughout its whple extent in such
a way that stationary waves are produced in it, like the Chladni's
figures seen on a metal plate strewed with sand when it is set into
vibration. The pattern of the movement, the ' sound-picture,' will be
different for each tone, since the interval between the waves will be
different. The hair-cells and auditory fibres of particular parts of the
organ of Corti will therefore be stimulated by the pressure of the mem-
brane, or escape stimulation, according to the position of the stationary
waves with reference to them for each note. In this way each sound-
picture will be printed, so to speak, upon the sensitive terminal appa-
ratus of the auditory nerve, as a letter is printed upon a piece of paper
by a type. The corresponding excitation pattern — i.e., the particular
distribution of cochlear fibres stimulated — is supposed to be associated
in consciousness with the appreciation of the pitch of the particular
note. Ewald has endeavoured to support his theory by showing that
fine membranes of the dimensions of the basilar membrane do yield
very distinct sound-pictures for different simple tones as well as for
complex tones. These can be observed with the microscope and photo-
graphed (Fig. 459).
One of the best-known theories of central analysis may be con-
veniently labelled the 'telephone theory,' in accordance with the simile
used by Rutherford. He supposed that the organ of Corti (or at any
rate the hair-cells) is set into vibration as a whole by all audible sounds,
and that its vibrations are translated into impulses in the auditory
nerve, which are the physiological counterpart of the aerial waves
and tiie waves of increased and diminished pressure in the liquids
of the labyrinth to which they give rise. Thus, a sound of 100
vibrations a second would start 100 impulses a second in the auditory
SMELL AND TASTE 1075
nerve; a loud sound would set up impulses more intense than a
feeble sound; and a complex wave, which is the resultant of several
sounds of different vibration-frequency, would also in some way or
other stamp the impress of its form on the auditory excitation wave ;
just as in a telephone every wave in the air causes a swing of the
vibrating plate, and thus sets up a current of
corresponding intensity and duration in the
wires. This theory evidently abandons the
doctrine of specific energy for the particular
case of the analysis of pitch, for it assumes
that differences of auditory sensation are
related to differences in the nature of the im-
pulses travelling up the auditory nerve, and
not merely to differences in the anatomical
connections (peripheral and central) of the
auditory nerve-fibres. It is unsatisfactory
because it takes no account of the remarkable
and suggestive structure of the telephone plate
• — i.e., of the organ of Corti — and gives no hint
of how the analysis is accomplished in the
central organ.
The range of hearing is very great. The
highest audible tone corresponds to 30,000 to
40,000 vibrations a second, the lowest to about pi^ 459. — photograph of a
30. Between these limits as many as 6,000 Sound-Picture (Ewald).
variations of pitch can be perceived.
Wien has elaborately investigated the question how the sensitive-
ness of the ear varies for tones of different pitch . A tone of 50 vibrations
a second, in order to be just heard, must have an intensity corre-
sponding to about 100 million times as much energy as is needed for a
tone of 2,000 vibrations. It is only on the extraordinary sensibility
of the ear for the range of tones used in ordinary speech that the
possibility of understanding speech depends when the circumstances
are unfavourable — e.g., at a great distance, or in the presence of much
stronger accompanying noises.
SECTION III. — SMELL AND TASTE.
Smell was defined by Kant as ' taste at a distance '; and it is
obvious that these two senses not only form a natural group when
the quality of the sensations is considered, but are closely associated
in their physiological action, especially in connection with the
perception of the flavour of the food. Their intimate relation is
further indicated by the fact that the cortical areas in which smell
and taste are represented lie close together or overlap each other
on the gyrus hippocampi and uncus (p. 968). The olfactory end-
organs in the mucous membrane of the upper part of the nostrils,
the so-called regio olfactoria, have been already described (p. 921).
In cases of anosmia, in which the olfactory nerve is absent or
paralyzed, smell is abolished; but substances such as ammonia and
acetic acid, which stimulate the ordinary sensory nerves (nasal
branch of fifth) of the olfactory mucous membrane, are still per-
ceived, though not distinguished from each other. In fact, the
so-called pungent odour of these substances is no more a true smell
1076 THE SENSES
than the sense of smarting they produce when their vapour comes
in contact with a sensory surface like the conjunctiva, or a piece
of skin devoid of epidermis.
It was at one time believed that odoriferous particles could not
be appreciated unless they were borne by the air into the nostrils;
but this appears not to be the case, for the smell of substances
dissolved in physiological salt solution is distinctly perceived when
the nostrils are filled with the liquid; and fish, as every line-fisher-
man knows, have no difficulty in finding a bait in the dark. The
odoriferous substances, even when air-borne, are dissolved in the
nasal secretion before they can affect the olfactory end-organs, and
it may be due to the peculiarities of this solvent that it is so difficult
to imitate a normal stimulation of the olfactory organs by solutions
experimentally introduced into the nose (Parker).
The substances which can affect the olfactory mucous membrane
can be divided into four groups :
1 . Those which act only on the olfactory nerves, the odours proper.
2. Substances which act at the same time on olfactory nerves, and on
nerves of common sensation (tactile nerves) — e.g., acetic acid.
3. Substances which act at the same time on the gustatory nerves.
4. Substances which act only on the nerves of common sen-
sation (tactile nerves) — e.g., carbon dioxide.
Zwaardemaker has classified the pure odours as follows :
(i) Ethereal odours, as those of fruits; (2) aromatic odours, as of
camphor or bitter almonds; (3) fragrant odours, as of flowers; (4) am-
brosial odours, as of amber or musk; (5) garlic odours, as of onion,
garlic, asafcetida; (6) empyreumatic, or burning odours, as of burnt
coffee or tobacco smoke; (7) caprylic or goat odours, as of sweat;
(8) repulsive odours, as the odour of the disease ozsena; (9) nauseating
odours, as of faeces or putrefying material.
The most interesting form of inadequate stimulation is electrical
excitation of the olfactory mucous membrane, which causes a sensation
like the smell of phosphorus. The sensation is experienced at the
kathode on closure and the anode on opening. As to the manner in
which the multitudinous adequate stimuli excite the olfactory nerves,
we can only suppose that they act as chemical stimuli. Smell and
taste are pre-eminently the ' chemical ' senses, as sight and hearing are
pre-eminently ' physical ' senses. But little is known of the relation
between the chemical constitution or physical properties of substances
and the quality of the odoriferous sensation which they excite, although
Haycraft has pointed out some interesting relations between the atomic
weights of certain elements and their power of exciting odours. The
number of distinct odours which can be perceived is so great that it is
scarcely conceivable that each is subserved by special olfactory fibres.
Marked changes occur in disease, and all odours need not be affected
to the same extent. Some may be almost normally perceived, while
relative or complete loss of smell exists as regards others. These and
other facts have given rise to the idea that there are several groups of
olfactory fibres, each concerned in the appreciation of a particular
odour or group of odours. Yet it has not proved possible to reduce them
to a limited number of fundamental odours and their combinations.
Acuteness of smell may be measured by arrangements called olfac-
tometers. Zwaardemaker 's olfactometer consists of a piece of india-
rubber tubing fitted inside a glass tube, through which air is drawn
SMELL AND TASTE 1077
into the nostrils. Another glass tube just fitting the rubber tube is
pushed inside it, so as to cover a portion of it. The minimum amount
of surface of the indiarubber tube which must be left exposed so that
the smell of the rubber may be perceived is a measure of the acuteness
of smell. To investigate other odours tubes of the corresponding
odorous substances can be constructed.
Taste. — The sense of taste is not so strictly localized as the sense
of smell. The tip and sides of the tongue, its root, the neighbour-
ing portions of the soft palate, and a strip in the centre of the dorsum,
are certainly endowed with the sense of taste ; but the exact limits of
the sensitive areas have not been defined, and, indeed, vary in
different individuals.
The nerves of taste are the glosso-pharyngeal, which innervates the
posterior part of the tongue, and the lingual, which supplies its tip
(see p. 925). The end-organs of the gustatory nerves are the taste-
buds or taste-bulbs, which stud the fungiform and circumvallate
papillae, and are most characteristically seen in the moats surrounding
the latter. They are barrel-like bodies, the staves of the barrel being
represented by supporting cells; each bud encloses a number of gusta-
tory cells with fine processes at their free ends projecting through the
superficial end of the barrel. They are surrounded by the end arboriza-
tions of the fibres of the gustatory nerves. Taste-buds are also found
on the posterior surface of the epiglottis and in the larynx. It has
been suggested that these form the afferent end-organs of a reflex
apparatus which guards the glottis against the entrance of food in
deglutition (Wilson). Epithelial buds, different from the olfactory
elements, also occur in the olfactory region of the nasal mucous mem-
brane. It is possible that the so-called nasal taste — e.g., the sweet
taste caused by chloroform when aspirated in not too small an amount
through the nose — depends upon these buds.
As to the properties in virtue of which sapid substances are
enabled to stimulate the gustatory nerve-endings, we know that
they must be soluble in the liquids of the mouth, and there our
knowledge ends. An attempt has been made by various authors
to connect the taste of such bodies with their chemical composition,
but researches of this kind have not hitherto yielded much fruit.
The number of distinct qualities of taste sensation is considerable,
but by no means so great as the number of qualities of olfactory
sensations, and they are more easily reduced to a few primary or
fundamental sensations. Sapid substances have generally been
divided into four classes as regards the fundamental sensations pro-
duced by them — viz.: (i) Sweet, (2) acid, (3) bitter, (4) saline.
All taste sensations seem to be combinations of these, or combina-
tions of one or more of them with olfactory sensations, or with sensa-
tions due to excitation of the ordinary sensory nerves of the tongue.
> Sweet and acid tastes are best appreciated by the tip, and bitter
tastes by the base, of the tongue. Differences have been detected
between individual papillae in their power of reaction to sapid sub-
stances which produce one or other of the fundamental sensation*.
Of 125 fungiform papillae tested with solutions of tartaric acid, sugar,
and quinine, 27 gave no sensation of taste. Tartaric acid evoked
1078 THE SENSES
its acid taste in 91 of the remaining 98, sugar its sweet taste in 79,
and quinine its bitter taste in 71 ; 12 reacted only to tartaric acid,
and 3 only to sugar (Ohrwall) . Such facts indicate, although they
do not definitely prove, the existence of specific receptors for each
of the fundamental taste sensations — i.e., gustatory end-organs,
which are easily excited by an adequate stimulus (acid, e.g., in the
case of an ' acid' taste-bud), with difficulty or not at all by an in-
adequate stimulus.
The form of inadequate stimulation most investigated is that pro-
duced when a constant current is passed through the tongue. An acid
taste is experienced at the positive, and an alkaline or bitter taste at the
negative pole ; and this is the case even when the current is conducted
to and from the tongue by unpolarizable combinations, which prevent the
deposition of electrolytic products on the mucous membrane (p. 731).
The sensations are due to stimulation of the gustatory end-organs and
not of the nerve-trunks.
Normal lymph, which bathes these end-organs, does not excite any
sensation of taste, but when the composition of the blood is altered in
disease or by the introduction of foreign substances, tastes of various
kinds may be perceived. Sometimes this may be due to the stimula-
tion of substances excreted in the saliva; but in other cases it seems
that, without passing beyond the blood and lymph, foreign substances
may excite the gustatory nerves.
Flavour embraces a group of mixed sensations in which smell and
taste are both concerned, as is shown by the common observation that
a person suffering from a cold in the head, which blunts his sense of
smell, loses the proper flavour of his food, and that some nauseous
medicines do not taste so badly when the nostrils are held.
In common speech, the two sensations are frequently confounded
with each other and with tactile sensations. Thus the ' bouquet ' of
wines, which most people imagine to be a sensation of taste, is in
reality a sensation of smell; the astringent ' taste ' of tannic acid is not
a taste at all, but a tactile sensation ; the ' hot ' taste of mustard is no
more a true sensation of taste than the sensation produced by the same
substance when applied in the form of a mustard poultice to the skin.
As already remarked, the substances which affect the olfactory end-
organs in air-breathing animals, like those which affect the gustatory
end-organs, must eventually go into solution before causing stimulation.
The most striking distinction between the two senses is the astonishingly
small concentration in which substances can elicit sensations of smell,
as compared with sensations of taste. Thus ethyl alcohol is a stimulus
for both smell and taste, but it can be recognized by smell in a dilution
24,000 times greater than the dilution necessary for taste (Parker).
SECTION IV. — CUTANEOUS AND INTERNAL SENSATIONS.
Under the sense of touch it was at one time usual to include a
group of sensations which differ in quality — and that in some in-
stances to as great an extent as any of the sensations which are
universally considered as separate and distinct — but agree in this,
that the end-organs by which they are perceived are all situated in
the skin, the mucous membranes, or the subcutaneous tissue.
They are more correctly designated ' cutaneous sensations.' Such
are the common tactile sensations — including pressure, tickling,
and itching — and the sensations of temperature, or, more correctly,
CUTANEOUS AND INTERNAL SENSATIONS
of change of temperature, or of warmth and cold. The sensation
of pain, although it cannot be absolutely separated from these, ought
not to be grouped along with them. It is called forth by the stimula-
tion of afferent nerve-fibres in their course; and it may originate,
under certain conditions, in internal organs which are devoid of
tactile sensibility, and the functional activity of which in their
normal state gives rise to no special sensation at all. The peculiar
sensation associated with voluntary muscular effort, to which the
name of the muscular sense has been given, also deserves a separate
place; for although it may in part depend on tactile sensations set
up through the medium of end-organs situated in muscle, tendon,
or the structures which enter into the formation
of the joints, other elements are, in all proba-
bility, involved.
The simplest form of tactile sensation is that
of mere contact, as when the skin is lightly
touched with the blunt end of a pencil. This
soon deepens into the sensation of pressure if
the contact is made closer; and eventually the
sense of pressure merges into a feeling of pain.-
Most physiologists agree that in the skin itself
four fundamental qualities of sensation are re-
presented— touch in the restricted sense (the
sensation elicited by light contact), warmth,
cold, and pain. Pressure is mainly a sensation
connected with the stimulation of structures
deeper than the skin — e.g., the sensation of
contact is abolished in cicatrices where the
true skin has been destroyed, while sensibility
to pressure persists — although the sensation of
light pressure may be to some extent re-
presented in the skin itself in association
with touch. In a somewhat diagrammatic
sense it may be said that the surface of the skin is divided into a
great number of very small areas, each of which is related especially
to one or other of the four fundamental sensations. Areas con-
cerned in one sensation are everywhere mingled with areas con-
cerned in the others. By appropriate methods it has been found
possible to determine the existence on the skin of the trunk and
limbs of not less than 30,000 ' warm-spots,' which always react to
stimulation by a sensation of warmth; 250,000 ' cold-spots,' which
react by a sensation of cold; and half a million touch-spots, whose
specific reaction is a sensation of touch. It is more difficult to
localize definitely bounded ' pain-spots,' partly because of the very
rich supply of pain-fibres to the skin. Yet there is reason to believe
that pain, like touch, warmth, and cold, is subserved by separate
Fig. 460. — Tactile Cor-
puscle from Skin of
Finger (Smirnow).
(Golgi preparation.)
The winding and in-
tersecting black lines
are the non-medul-
lated endings of the
one or more nerve-
fibres that enter the
corpuscle.
io8o THE SENSES
receptors. The simplest assumption which will satisfactorily
account for the distribution of the four fundamental cutaneous
sensations is that the skin is supplied with four kinds of nerve-
fibres, anatomically as well as functionally distinct. Some fibres
minister to the sensation of cold, others to that of warmth, others
to that of touch, and others still to pain. And just as stimulation
of the optic nerve gives rise to a sensation of light, so stimulation
of any one of the cutaneous nerves gives rise to the specific sensa-
tion proper to the group to which it belongs. The existence of
different forms of sensory end-organs in the skin and other tissues
(tactile or touch-corpuscles, corpuscles of Pacini, end-bulbs of
Krause, etc.) points in the same direction. The end-organs of the
touch sensations are believed to be the ring-like arrangements of
non-medullated nerve-fibres encircling the hair-follicles, and in
parts of the skin devoid of hairs the corpuscles of Meissner (v. Frey)
Touch-spots can easily be demonstrated by touching the skin lightly
with some small object such as a hair. The most exact quantitative
observations have been made by means of v. Frey's hair aesthesiometer.
This consists of a handle in which hairs of different diameter can be
fixed. The area of the cross section of each hair is measured under the
microscope, and the pressure necessary to bend it is determined by
pressing it upon the scale-pan of a balance. The pressure in milli-
grammes, divided by the cross section in square millimeters, gives the
pressure per square millimetre, which, according to v. Frey, permits
hairs to be chosen so as to give a uniform intensity of stimulation or
a variable intensity, according to the object of the investigation. Many
observers, however, believe that it is more accurate to take no account
of the pressure per unit of area, but to graduate the hairs according to
the total pressure needed to bend them. When touch-spots ascer-
tained in this way are excited, by an inadequate stimulus — e.g., an
alternating current of minimal strength, applied by the unipolar
method through the head of a pin as an electrode — they still respond
by their characteristic or specific reaction — namely, a sensation of
touch — in the case supposed, a vibrating sensation like that caused by
a tuning-fork in contact with the skin. In the spaces between the
touch-spots the sensation produced by the same strength of current, or
even by a weaker current, is not one of touch, but a painful pricking
sensation which has no vibratory character, but is permanent as long
as the current lasts.
The spots most sensitive to touch lie close to the hairs on their
' windward ' side — i.e., on the side away from which they slope. The
minimum pressure necessary to evoke a sensation of contact is not the
same for every portion of the skin. The forehead and palm of the
hand are most sensitive. According to Lombard the cutaneous pres-
sure and tickle sensations called out by delicate mechanical stimuli
(hairs, etc.), do not arise from the same spots.
If two points of the skin are touched at the same time there is a
double sensation when the distance between the points exceeds a cer-
tain minimum, which varies for different parts of the sensitive surface.
Practice increases the acuity of touch for the two points test. Even
in a few hours it may be temporarily quadrupled on some parts of the
skin. Since at the same time it is increased in the corresponding part
of the opposite side of the body, it is argued that the modification takes
place in the central nervous system, not in the end-organs themselves.
CUTANEOUS AND INTERNAL SENSATIONS
1081
Few of the internal organs are supplied with tactile nerves. The
mucous membrane of the alimentary canal from the upper end of the
oesophagus to the junction of the rectum with the anal canal is in-
sensitive to tactile stimulation (Hertz). The movements. of a tape-
worm in the intestines are not recognized as tactile sensations, nor the
movements of the alimentary canal during digestion, nor the rubbing
of one muscle on another during its contraction.
Number of Touch-
Spots per Sq. Cm.
Mean Threshold Value
. Grammes
Sq. Mm.
Wrist (ventral surface)
28
I'l
Wrist (dorsal surface) ...
28
1-2
Forearm .....
16
I'2
Elbow
12
i'3
Upper arm -
10
*'4
Foot (dorsal surface) -
23
1-2
Leg (ventral surface) ...
5
2-1
Thigh (ventral surface)
14
ITS
Breast •
21
2-7
Back
26
4'3
(Kiesow) .
Pressure is only perceived when it affects two neighbouring areas to
a different degree. Thus, the atmospheric pressure, bearing uniformly
on the whole surface of the body, causes no sensation ; we are so entirely
unconscious of it that it needed the inspiration of genius to discover
it, and the persistence of genius to force the discovery on the world.
When the finger is dipped in a trough of mercury at its own temperature,
no sensation is perceived except a feeling of constriction at the surface
of the liquid. The perception of light pressure and of the form and size
of objects in contact with the skin is believed to be due to the touch-
spots. Deep pressure, however, is appreciated, not by the skin, but
through sensory end-organs in deeper structures — probably, e.g.,
Pacini's corpuscles and the muscle-spindles (Fig. 471, p. 1096).
Distance at which Two Points
can be distinctly felt, in Mm.
Point of tongue -
I'l
Palmar surface of third
phalanx of finger
2-2
Dorsal surface of third
phalanx of finger
6-7
Tip of nose -
6-7
Back ....
II-2
Eyelids -
1 1 -2
Skin over sacrum
40-5
Upper arm -
67-6
Sensations of Warmth and Cold. — When a body colder or hotter
than the skin is placed on it, or when heat is in any other way
io82
THE SENSES
withdrawn from or imparted to the cutaneous tissues with sufficient
abruptness, a sensation of cold or warmth is experienced. And
when two portions of the skin at different temperatures are put in
contact, we feel that, relatively to one another, one is warm and
the other cold. But it is worthy of remark that it is only difference
of temperature (or, perhaps, rather the
rate at which heat is "being gained or
lost by the skin), and not absolute
height, which we are able to estimate
by our sensations. Thus, a hand which
has been working in ice-cold water will
feel water at 10° C. as warm; whereas it
would appear cold to a warm hand.
Blix, Goldscheider, and others have
shown that the whole skin is not en-
dowed with the capacity of distin-
guishing temperature, but that the
temperature sensations are confined
to minute areas scattered over the
cutaneous surface. The great majority
of these are 'cold* spots — i.e., respond
to stimulation only by a sensation of
cold — while a smaller number are
' warm ' spots, and respond only by a
sensation of warmth (Fig. 461). These
spots can be mapped out by bringing
into contact with the skin small pieces
of wire at a temperature a few degrees
above or below that of the skin. With
such mild stimuli a response can
generally be obtained only from one
kind of spot — that is, the cold wire
stimulates only the cold and not the
warm spots, and vice versa — but with
much more intense thermal stimuli —
say, temperatures of 45° to 50° C. —
not only do the warm spots respond
with the appropriate sensation, but
the cold spots respond with a sensation
of cold. This is well seen when a
beam of sunlight is focussed succes-
sively on a warm and a cold spot. Inadequate stimuli (mechanical
and electrical) also evoke the specific response of warmth from
warm spots, and of cold from cold spots.
When the hand is put into water at the temperature of the skin,
and the water slowly heated, the warm spots are at first alone stimu-
Fig. 461. — 'Warm' and 'Cold'
Areas on Skin (Goldscheider).
The areas are mapped out on
the palm of the left hand. In
the upper figure the relative
sensitiveness to warmth is
represented by the depth of the
shading, the black areas being
most sensitive, then the lined
areas, then the dotted, and
last of all the white areas. In
the lower figure the relative
sensitiveness to cold stimuli is
shown in the same way.
CUTANEOUS AND INTERNAL SENSATIONS 1083
lated, and the sensations of lukewarm and then of warm are experi-
enced. When the temperature of the water reaches 45° C., the
quality of the sensation changes to ' hot.' At a still higher tempera-
ture the sensation becomes painful or burning. The most probable
explanation of these facts is mentioned below (p. 1084).
It is not only of physiological interest, but of practical importance,
that most mucous membranes are in comparison with the skin but
slightly sensitive to changes of temperature. Only towards the ends
of the alimentary canal, in the mouth, pharynx, oesophagus, and anal
canal, is it possible to elicit warmth or cold sensations. There is some
difference of opinion whether a blunted sensibility appears in the
stomach also. The uterus, too, is quite insensible to moderate heat;
and hot liquids may be injected into its cavity at a temperature higher
than that which can be borne by the hand, without causing inconveni-
ence— a fact which finds its application in the practice of gynaecology
and obstetrics. It is, indeed, obvious that in the greater number of
the internal organs the conditions necessary for stimulation of tem-
perature nerves, even if such were present, could hardly ever exist.
It has already been mentioned that changes of external temperature
exert a remarkable influence on the intensity of metabolism -(p. 693),
and it has been supposed that this is brought about by afferent impulses
travelling up the cutaneous nerves. We have-also seen that for certain
kinds of stimuli the excitability of nerve-fibres is increased by cooling
(p. 784). It is possible that this is the case for the fibres in the skin
which are concerned in the regulation of the production of heat, and it
has been suggested that this fact may have a bearing on the reflex
regulation of temperature (Lorrain Smith) .
Pain Sensations. — While the cold and the warmth spots are irregu-
larly distributed over the skin in more or less compact groups, and
the touch sensations are intimately associated with the hair follicles,
the pain spots are more uniformly spread, and at the same time set
closer together. In parts of the body where but one of these
elementary forms of general sensibility is present, as in the central
parts of the cornea and in the dentine and pulp of the teeth, it is
always pain.
In certain situations pain and temperature sensibility are found
together, but not touch — e.g., at the margin of the cornea and on
the conjunctiva.
In general, the skin is far more sensitive to pain than the deeper
structures. The most painful part of an operation is generally the
stitching of the wound. The cutting of healthy muscle causes no
pain. In an operation in which an artificial connection was estab-
lished between the stomach and the small intestine (gastro-enter-
ostomy), and in which no anaesthetic was administered, the only
pain of which the patient complained was produced by the incision
in the skin (Senn). This, however, does not prove that the
abdominal viscera are devoid of pain nerves, for it has been shown
in animals that exposure of the intestines, etc., as in laparotomy,
leads to a rapid depression (exhaustion ?) of the sensibility for pain
1084 THE SENSES
(Kast and Meltzer). In the intact animal and human being painful
impressions can unquestionably be excited in the viscera by adequate
stimuli (p. 901). Thus, the spasmodic contraction of the intestines
and stomach causes the intense pain of colic and gastralgia. Labour
is an example of a strictly physiological function which is the
occasion of severe pain. It would appear from the observations
of Hertz that the only immediate cause of true visceral pain, as
distinguished from referred pain (p. 891) is distension acting on the
muscular coat of hollow organs and on the fibrous capsule of solid
organs. The sensation of pain in the alimentary canal is due to a
more rapid or a greater distension than that which constitutes the
adequate stimulus for the sensation of fulness. Visceral sensi-
bility seems to be exaggerated in such conditions as hypochondri-
asis, neurasthenia, and anaemia. Tissues normally insensible, or,
rather, but slightly sensible, to pain may become acutely painful
when inflamed.
The question has been raised whether the sensation of pain can
be caused by excessive stimulation of the nerves of common tactile
sensibility, or of the nerves that subserve the sensations of coolness
and warmth. It is true that when the skin is lightly touched in
the region of a touch-spot with a small object at its own temperature
the sensation is one of pure touch. As the pressure is increased, a
sensation of pressure, quite distinct from that of contact, may be
felt ; and if the pressure is stih1 further increased, a sensation of pain
may be elicited. It seems to be quite clearly made out that the
pressure sensation in this case is due not to excessive stimulation
of the touch-nerves, but to stimulation of the specific pressure-
nerves when the threshold is reached. The most natural explana-
tion of the pain sensation is that it, too, is due to excitation of the
nervous apparatus for pain. Similarly (as was stated on p. 1082),
if the skin is raised to higher and higher temperatures, the response
is at first a pure sensation of warmth, increasing in intensity without
changing its quality. When a certain temperature (about 45° C.)
is exceeded, the sensation changes to ' hot,' either because a pain
element is now added to the pure thermal sensation, or because the
cold spots are now stimulated as well as the warm spots, and mingle
their specific response (cold sensation) with that of the warm spots.
Further increase of the temperature will cause distinct pain, the
sensation assuming a burning character. When a cold spot is
tested with decreasing temperatures, an analogous series of sensa-
tions is run through, the pure sensation of coolness eventually giving
place to cold, intense cold, and finally pain. Here, also, it is simplest
to assume that the pain sensation is caused not by excessive stimu-
lation of warm or cold spots, but by excitation of the specific pain-
spots. In any case, there is no doubt that afferent ' pain ' fibres
exist which are anatomically distinct from the fibres of tactile and
CUTANEOUS AND INTERNAL SENSATIONS 1085
of temperature sensations. For the conducting paths in the spinal
cord are not the same for tactile and for painful impression^. And
in certain cases of disease sensibility to pain may be lost, while
tactile sensations are still perceived ; or, on the other hand, pain may
be felt in cases where tactile sensibility is abolished. Loss of tem-
perature sensation, however, is usually accompanied by loss of
sensibility to pain. When a nerve is compressed, the sensibility
of the tract supplied by it disappears for cold sooner than for
warmth.
Pain has been denned as ' the prayer of a nerve for pure blood.' The
idea is not only true as poetry, but, with certain deductions and limita-
tions, true as physiology; that is to say, pain, as a rule, is a sign
that something has gone wrong with the bodily machinery; freedom
from pain is the normal state of the healthy body. Physiologically,
pain acts as a danger-signal. It points out the seat of the mischief,
and even, in certain cases, by compelling rest, favours the process of
repair. Thus, the surgeon has sometimes looked upon pain as ' Nature's
splint.' But, as a matter of fact, a certain amount of pain occurring
at intervals is not incompatible with high health ; and probably nobody,
even when accidents and indiscretions of all kinds are avoided, is en-
tirely free from pain for any considerable time. Sometimes, indeed,
the mere fixing of the attention on a particular part of the body is
sufficient to bring out or to detect a slight sensation of pain in it; and
it is matter of common experience that a dull continuous pain, like that
of some forms of toothache, is aggravated by thinking of it, and relieved
when the attention is diverted.
As to the sensations of tickling and itching, it is enough to say
that physiologists are not agreed whether they represent specific
sensibilities subserved by special nerves distinct from those of touch
and pain, or merely modifications or mixtures of these sensations.
Phenomena observed after Section of Cutaneous Nerves. — The
innervation of the skin can be explored not only by appropriate
stimulation of the normal skin, but by study of the defects or altera-
tions of sensibility which follow section of a cutaneous nerve, and
which may be observed at different stages in its regeneration. In
recent years this has proved a fruitful method, especially in experi-
ments made by skilled observers in whom one or more cutaneous
nerves were intentionally divided.
An extensive investigation was made by Trotter and Da vies.
They divided at different times, extending over more than a
year, no fewer than seven of their own cutaneous nerves, in-
cluding the internal saphenous at the knee, the great auricular,
three divisions or branches of the internal cutaneous of the arm
just below the elbow, and a branch of the middle cutaneous of
the thigh. The operations were purposely done at such intervals
as would allow the experience gained in investigating one area
to be applied to others. About a quarter of an inch was cut out
of each nerve, and the ends then sutured together. ' In each
io86
THE SENSES
case the area of skin supplied by the nerve showed defects in seven
distinct functions: four sensory— namely, sensibility to touch, cold,
heat, pain — and three motor — namely, vaso-motor. pilo-motor,
sudo-motor (sweat-secretory). The sensory changes showed a
central area of profound loss, an area of moderate extent surrounding
STMHIHH ovniMt
Fig. 462. — Areas of Altered Sensibility produced by Section of all Three Branches
of the Internal Cutaneous Nerve of the Left Forearm (Trotter and Davies).
(Reduced by Two-thirds.) The thick lines show the areas of anaesthesia to the
brush. The thick continuous lines enclose the areas of the anterior and posterior
branches. The thick broken line and heavy shading mark the area of the in-
crease in anaesthesia which followed section of the middle branch. The thin
lines show the areas of minimal hypoaesthesia — i.e., the ' stroking outline.' The
complete oval outline is the ' stroking outline ' which followed section of the pos-
terior branch. The large addition to the oval on the right of the diagram shows the
increase in the ' stroking outline ' which followed section of the anterior branch.
fhe thin broken line and fine shading show the additions to the ' stroking out-
line ' produced by division of the middle branch.
this of partial loss, and a large area in which a qualitative change
could be alone detected.' The maximal extent of change, and
therefore the outer boundary of this third area, can be mapped out
by getting the subject to determine by light, stroking touches the
area which feels in any way unnatural when he touches it himself.
The most common feeling is that the skin has become smoother at
CUTANEOUS AND INTERNAL SENSATIONS
1087
the boundary as the stroking finger crosses it, coming from the
normal skin. This area is always much larger than the area in-
cluded in it, in which by quantitative methods — e.g., the use of a
.very fine camel's-hair brush, or more exactly by the v, Frey hairs —
the sensibility to touch can be shown to be diminished (region of
hypoaesthesia to touch) (Fig. 4^2).
For a variable distance within the ' stroking outline ' the hypo-
Fig. 463. — Middle Cutaneous: Left Thigh (Trotter and Davies) (reduced by One-
third Linear). Twenty-six days after section. Results of examination with
v. Frey hairs. Touch spots marked • responded to hair of 280 milligrammes'
pressure; those marked o to hair of 800 milligrammes; and those marked -f- to
hair of 2,280 milligrammes. The continuous line marks the limit within which
there was anesthesia to the camel's-hair brush.
aesthesia for tactile stimuli is so slight that it cannot be detected
with the brush or with cotton-wool, or even with the v. Frey hairs.
Like those of normal skin, 90 per cent, of its hair-bulbs respond to
a hair exerting a pressure of 70 milligrammes, and the remaining
10 per cent, to hairs exerting a pressure of 140 or 280 milligrammes.
Inside this zone of minimal hypoaesthesia the defect of sensibility
io88
THE SENSES
rapidly increases as we pass inwards, each line of hair bulbs re.
quiring a heavier pressure than the line external to it, till at
last 3i or 4 grammes' pressure is needed to cause a sensation of
touch, and inside of this line of hairs the skin does not respond
at all (Fig. 463).
For thermal sensibility there is also a region of complete anaes-
thesia and a region of partial anaesthesia. The best way of out-
Fig. 464. — Middle Cutaneous: Left Thigh (Trotter and Davies). Twenty-one days
after section. Results of examination with temperature of o° C. On spots
marked • stimulus was felt as cold; on spots marked o it was felt as cool. The
blank area is that of thermal anaesthesia. The continuous outline marks the
limit within which there was anaesthesia to the camel's-hair brush.
lining these is the use of a temperature of o° C. as the stimulus
(Fig. 464).
Outside the zone of complete thermal anaesthesia there is a region
in which temperature sensations are distinctly elicited, but do not
possess the normal intensity, the temperature of o° C., for example,
being felt only as cool, and not as cold. The outer limit of this
region is the line at which the temperature of o° C. is first felt as
CUTANEOUS AND INTERNAL SENSATIONS
1089
we work inwards from the normal skin to yield the sensation of
cool instead of cold. Similarly, the outer limit of thermo-hypo-
aesthesia can be determined by using a high temperature (50° C ).
It is the line at which the sensation of hot yielded by the normal
skin gives place to the sensation of warm. The two boundaries
correspond closely when allowance is made for the separate grouping
of cold and warmth spots on the normal skin.
Fig. 465. — Middle Cutaneous (External Branch): Left Thigh (Trotter and Davies).
Twenty-three days after section. Results of examination with algometer (an
arrangement by which a needle is pressed against the skin by a hair whose
pressure value has been determined). Spots marked • reacted by sensation of
pain to pressure of 1,860 milligrammes (normal threshold); spots marked o re-
quired 2,280 milligrammes. The continuous line marks the area within which
there was anaesthesia to the camel's-hair brush.
The investigation of the sensibility of the skin areas for painful
stimuli is complicated by the fact that during a certain period,
from about the second to the sixth week after division of the nerve,
hyperalgesia (increased sensitiveness to painful impressions) may
appear. This, however, does not seem to be a consequence of any
sensory loss, but rather a complication due to an irritative change.
When this is taken account of, it is found that the defect of sensi-
bility to pain after nerve section resembles the defects of sensi-
69
logo THE SENSES
bility to touch and temperature, showing a central area of absolute
anaesthesia surrounded by a zone of partial loss, which is slight
towards the outer boundary, but increases as we pass inwards
(Fig. 465)-
After section of a nerve function is recovered only as a result of
regeneration. This is true of all the sensory functions of the skin
and of the pilo-motor and sudo-motor functions. Vaso-motor tone
in the affected area is restored much sooner than the other functions.
This rapid recovery probably depends upon a local compensatory
mechanism, and not upon regeneration of the vaso-motor fibres.
Recovery of all the functions dependent upon regeneration begins
about the same time, and this recovery progresses over the area at
about the same rate for all, although the rate at which they progress
towards normal acuity is different.
Sensibility to touch probably appears a little earlier than sensi-
bility to cold and pain. Yet the recovery of touch does not progress
so fast, and for a while a given zone of the recovering area remains
hypoaesthetic (less sensitive than normal) to touch, while to cold
and pain it soon becomes even hypersensitive. The most remark-
able peculiarities of a recovering area are : (i) This qualitative
change, in virtue of which cold, pain, and the pain element of heat
are intensified, while touch is little altered, although more difficult
to elicit ; (2) the reference of sensations, not to the point stimulated,
but to distant parts of the area.
'When a spot which has developed this peripheral reference is
touched, one of two possibilities may occur: either the touch is
felt locally, and is referred as well, or nothing is felt locally, and
the touch is felt in the area of peripheral reference. The region
in which the referred touch is felt is always at the edge of the most
peripheral part of the anaesthesia/ perhaps more than a foot away
from the spot actually touched. The peripheral reference of cold
is even more striking, particularly in the remarkable intensity of
the referred sensation.
Peripheral reference occurs also with pain. ' The referred pain
shows three well-marked qualities: it is, proportionately to the
stimulus, very intense ; it does not reproduce a normal sensation
with the exactitude found in the case of touch or cold, but has a
special quality of strangeness and unpleasantness, such as no pin-
prick on normal skin can give; finally, it produces an almost irre-
sistible desire on the part of the subject to rub or scratch the region
in which it is felt.' As recovery proceeds the local sensory response
becomes more distinct, and the abnormal quality of both local and
referred sensations fades. But ' while peripheral reference is the
earliest phenomenon of recovery, it persists until recovery is so far
advanced that hypoaesthesia is scarcely detectable by any quanti-
tative methods.'
logi
The work of Head, who was the pioneer in this method of investiga-
tion, must also be mentioned. He found that when the median nerve
was divided in his own arm, recovery of sensation began with the
restoration of sensibility to pain and to extreme degrees of heat and
cold ; but the hand still remained for a time as insensitive as before to
such stimuli as slight touch. In the parts which had regained their
sensibility to severe stimuli, like pricking and extremes of heat and cold,
the sensation radiated widely, was referred to remote parts, and could not
be accurately localized. This form of sensibility Head calls protopathic.
As the nerve recovered further, a second form of sensibility appeared,
associated with accurate localization of cutaneous stimuli and dis-
crimination of two compass points. Light touch and moderate degrees
of heat and cold could now be again appreciated. This form of sensi-
bility he terms epicritic. A third form of sensibility (deep sensibility}
was investigated after complete division of the radial and external
cutaneous nerves at the elbow. The radial half of the arm and back
of the hand became totally insensitive to cutaneous stimuli, but re-
tained their sensibility to pressure or to any stimulus which deformed
the subcutaneous structures, as well as their power of localization of
such stimuli. The afferent fibres upon which this deep sensibility
depends must run with the motor nerves. According to Head, the
other two forms of sensibility (protopathic and epicritic) also depend
on two separate systems of nerves, of which the protopathic is the older
in the phylogenetic sense, and has a wider distribution. It is assumed
that the protopathic fibres regenerate more easily and speedily than the
epicritic or than the motor nerves of voluntary muscle. The proto-
pathic fibres are supposed by Head to exert a trophic influence. A
part deprived of its nerve-supply is liable to injuries, and the sores so
produced heal slowly. But as soon as ' protopathic ' sensibility returns
to the part, they heal rapidly, even in the absence of all epicritic sensa-
tion. The intestine is described as possessing 'protopathic,' but not
'epicritic,' sensibility — i.e., it reacts to extremes of heat and cold, but
not to moderate heat and cold or light touch.
Quite recently an elaborate study of the loss and return of the
skin sensations after section of a cutaneous nerve has been made by
Boring. His work is distinguished from that of all previous ob-
servers by the fact that he brought to his task the training of a
professional psychologist, and that he studied in detail for fifteen
months the area of skin with whose innervation he intended to
interfere. Section of the nerve chosen (the anterior branch of the
internal cutaneous nerve in the forearm) caused anaesthesia and
hypoaesthesia of a relatively small area of skin (on the volar aspect
of the forearm near the wrist), so that it was possible to make an
intensive study of it, and the observations were continued for more
than 1,000 days after the operation. Points on the affected area
were identified by reference to a series of points tattooed on the
skin represented by crosses in Fig. 466.
The sensations studied, in addition to those of warmth and cold,
were the four qualities which appear upon mechanical stimulation
of the skin: Contact, cutaneous pressure, subcutaneous or deep
pressure and pain. Boring uses the terms ' tickle-contact/ ' pene-
trating pressure,' ' dull pressure/ and ' sharpness ' for these quali-
THE SENSES
ties. The localization of the sensations and the power of discrimi-
nating two points were also investigated.
The general tendency during recovery was from anaesthesia or
hypoaesthesia through decreasing degrees of hypoaesthesia to normal.
Warmth and cold, however, passed from hypoaesthesia through a
stage of hyperaesthesia on their way to normal. Pain, pressure, and
cold approached normality at about the same rate, but in compari-
son with these the return of warmth sensation was much delayed
Fig. 466. — Volar Aspect of Left Forearm, showing Affected Region in Outline.
The larger area was that marked off by the subject with the camel's hair
brush as insensitive. The inclosed smaller area is that which was marked off
when the experimenter manipulated the brush, and the subject with closed
eyes reported when he felt anything at all. This smaller area was taken as
the region of greatest change in sensitivity, and the experiments on localization
and the discrimination of two points were mainly made within this area. The
dotted line shows the approximate course of the nerve, divided at S. The
horizontal and vertical lines dividing the area into small squares were impressed
by a rubber stamp on the skin, to facilitate identification of points. The
position of each point stimulated was fixed with reference to these rectilinear
co-ordinates, the tattooed point represented by the Maltese cross being taken
as the origin, and the distances in mm. measured in the central (C), peri-
pheral (P), radial (R), and ulnar (U) directions (Boring).
For all four the distribution of sensitivity over the skin was irregular
and patchy, and no definite boundaries could be drawn. In general,
however, immediately after division of the nerve the central zone
of the affected area was practi _:ally anaesthetic as regards cutaneous
sensation. This was surrounded by a zone of decreased sensitivity.
In the return of sensibility the outer zone preceded the inner.
No new modes or qualities of sensation were observed at any time,
although ' a number of unusual sensory complexes, which might be
described by an untrained observer as new sensations, were noted.
CUTANEOUS AND INTERNAL SENSATIONS 1093
. . . The most striking single experience was the intense algesic cold,
which occurred when the skin was hyperaesthetic to cold.' Deep
sensibility to pressure and pain was not altered. Localization
of pressures (of 20 gm.) and discrimination of two pressures (two-
point discrimination) remained unaffected.
This study on the whole confirms that of Trotter and Davies. How-
ever, the larger outer or third area defined by the so-called ' stroking
outline ' of Trotter and Davies is probably not an area of sensory
abnormality at all, but merely an area in which a physical change in
the skin, due, e.g., to some interference with the action of the sweat
glands, is appreciated by the stroking finger. This follows from the
fact that it can be mapped out approximately by an observer who
strokes it with his own finger without asking the subject to report his
sensations. The results of Boring's investigation are quite opposed to
the most essential of Head's conclusions. No evidence was found in
favour of Head's distinction between epicritic and protopathic sensi-
bility, and weighty evidence against it. There does not seem to be
any real necessity in the observed facts for introducing so revolutionary
a conception of the nervous system. Nor is it possible to uphold the
distinction in any thoroughgoing fashion for all structures. For in-
stance, in abdominal operations performed under local anaesthesia it
has been seen that the parietal peritoneum is quite insensitive to touch,
pressure, and temperature stimuli, including extreme temperatures
(Ramstrom), while pain is caused by traction on it. Its sensibility
is therefore neither purely epicritic nor purely protopathic in Head's
sense. In like manner the mucous membrane of the mouth, in which
sensibility only to touch and temperature is present, conforms entirely
to neither type. Its sensibility is not alone epicritic, since it responds
to extreme temperatures, nor is it purely protopathic, since a pin-prick
produces no painful sensation. These terms and the theory associated
with them should be dropped.
Localization of Cutaneous Sensations. — We not only perceive the
quality and estimate the intensity of sensations of touch, warmth, cold
pain, etc., but are able, more or less accurately, to localize the part of
the body from which the sensory impressions come. In other words,
two impressions from different parts of the body, although identical
in quality and intensity, are nevertheless stamped with a distinctive
something, which may be called the local sign. This power of localiza-
tion is not equal for all portions of the body nor for all kinds of sensa-
tions. It is best developed for touch (in the restricted sense), and all
the varieties of common sensation are better localized on the skin than
in any of the deeper structures. The precise mechanism of the localiza-
tion is unknown. But we must suppose that each peripheral area is
' represented ' in the brain, so that the arrival of afferent impulses from
it affects particularly the related cerebral area. The brain, therefore,
so to speak, associates excitation of a given cerebral area with stimula-
tion of the corresponding peripheral area, and thus not only recognizes
the quality and quantity of the resultant sensation, but also localizes
it; just as a waiter who watches the bell-indicator not only learns how
a bell has been rung, whether once or twice, peremptorily or languidly,
but also in which room it has been rung. If, to pursue the illustration
a little farther, he is aware that two rooms are connected with one
bell, but that one of the rooms is scarcely ever occupied, he associates
the ringing of the bell with a summons from the other room even when
it happens to be rung from the usually vacant room. In like manner
1094
THE SENSES
the brain seems to connect the arrival of sensory impulses from the
internal organs, which have few sensory fibres, and these perhaps not
often stimulated, with excitation in a related cutaneous region, from
which it is constantly receiving sensory impressions. The fact already
mentioned (p. 892), that in disease of internal organs the pain is re-
ferred to some portion of the skin, ma)' be thus explained.
An attempt has been made to explain certain illusions of touch
on the theory that just as an object is recognized as single by the eye
when its images fallen corresponding points of the two retinae (p. 1037),
so an object is recognized as single by the fingers when it comes into
contact with corresponding points or rather areas of the skin. These
are the areas which experience has taught us are in contact with an
object when it is held in the natural way. When now a single object is
made, by placing the fingers in an unnatural position, to touch areas
which could ordinarily be touched at the same time only by two or
by three objects, we experience the sensation of contact with two or with
three objects.
Fig. 467. — Illusion of Touch of
Aristotle. A small object placed
between the index and middle
fingers, crossed as shown, is felt
as two objects (Wassenaar).
Fig. 468. — An Object placed in contact with
the Index, Middle and Ring Fingers,
crossed as shown, is felt as three objects
(Wassenaar).
It is through the localization of touch sensations that the size and
form of objects in contact with the skin are perceived in the absence
of other than the cutaneous sensations, and especially in the absence
of visual and muscular sensations (stereognosis).
Muscular Sensations (Muscular Sense), etc. — Sometimes, although
rather loosely, grouped together as muscular sensations, are a number
of forms of sensation of which our knowledge is much less accurate
than it is in the case of the fundamental skin sensations. Among
these may be mentioned especially (i) the sensations by which the
position in space of the body as a whole or of particular parts is recog-
nized in the absence of visual sensations; (2) the sensations associated
with movements, passive as well as active ; (3) the sensations associated
CUTANEOUS AND INTERNAL SENSATIONS 1095
with resistance to movement. In none of these groups are we dealing
with purely muscular sensations; cutaneous tactile sensations and
pressure sensations elicited from other structures than muscles are
also involved.
Voluntary muscular movements are accompanied with a peculiar
sensation of effort, graduated according to the strength of the con-
traction, and affording data from which a judgment as to its amount
and direction may be formed.
It has been shown, however, that when pressure sensations are elimi-
nated or reduced to a minimum by enclosing the arm, held horizontally,
in a rigid apparatus such as that shown in Fig. 469, the moments of
rotation of a weight* fastened at different distances from the shoulder
can be discriminated v.'ith great exactness. The sensation of effort is
therefore an independent sensation (v. Frey).
Fig. 469- — Apparatus for Arm for Testing Muscle Sense. At the right is shown a lead
weight which can be placed on either of the hoops of the apparatus (v. Frey).
Some writers have supposed that this so-called muscular sense does
not depend upon afferent impulses at all, but that the nervous centres
from which the voluntary impulses depart take cognizance, retain a
record, so to speak, of the quantity of outgoing nervous force ; that the
effort which we feel in lifting a heavy weight is an effort of the cells
of the motor centres from which the groups of muscles are innervated,
and not of the muscles themselves.
But although this feeling of central effort or outflow (we can hardly say
of central fatigue) may be a factor, it cannot be doubted that the brain
is kept in touch with the contracting muscle by impulses of various
kinds which reach it by different afferent channels.
The corpuscles of Pacini, which exist in considerable numbers in the
neighbourhood of joints and ligaments, and in the periosteum of bones,
Fi?. 470. — Nerve-Ending in Tendon near the Insertion of the Muscular
Fibres (Go}e\\.
Fibres (Golgi).
would seem well fitted to play the part of end-organs for the tactile
sensations caused by the movements of flexion, extension, or rotation
of one bone on another, which form so large a portion of all voluntary
* With the arm horizontal the moment is the product of the weight by its
distance from the shoulder joint (see p. 749).
rog6
THE SENSES
muscular movements. And it has been stated that paralysis of these
bodies in the limbs of a cat by section of the nerves going to them
causes a characteristic uncertainty of movement which suggests that
something necessary to normal co-ordination has been taken away.
Tendons also possess afferent nerve-fibres, which terminate by breaking
up into reticulated end-plates (Fig. 470). We have already seen that
the skeletal muscles possess numerous afferent fibres (p. 941). Some
of these must be nerves of ordinary sensation. For, although when a
muscle is laid ba: * in man and stimulated electrically, the sensation
does not in general amount to actual pain, it is capable, under the
influence of strong stimuli, of taking on a painful character. And
nobody who has felt the severe and sometimes almost intolerable pain
of muscular cramp would be likely to deny the existence of sensory
muscular nerves. But after deducting these, we must assume that a
m'n.b.
Fig. 448. — Muscle Spindle (after Ruffini). c, sheath of the spindle ; n.tr., trunk
of nerve, which sends fibres through the sheath into the spindle, where they
form endings (pr.e., s.e., pl.e.) of various kinds; m.n.b.. bundle of motor fibres.
large proportion of the afferent nerves of muscle have other functions,
and among them may be the conveyance of impulses connected with
the muscular sense. The muscle-spindles or neuro-muscular spindles
(Fig. 471), peculiar structures which occur in large number in most
of the skeletal muscles, and have been carefully studied by Huber,
Sihler, Ruffini, and other observers, are the terminations of many of
the sensory fibres. They are long narrow bodies, with a thick sheath
of connective tissue enclosing fine striped muscular fibres. Medul-
lated nerve-fibres enter the spindle, and there, dividing into branches
and losing their medullary sheath, form endings of various kinds around
and between the muscular fibres. It is possible that in contraction
of the muscles the nerve-fibres in the spindles are compressed, and thus
mechanically stimulated.
In the spinal cord these impulses are conducted up through the
posterior column; and, although less is known as to the paths they
follow in the higher parts of the central nervous system, it is certain
that there is some afferent bond of connection between the cortical
motor areas and the muscles which they control (p. 963).
Tactile sensations set up in the skin or mucous membrane lying
over contracting muscles may also help the nervous motor mechanism
in appreciating and regulating the amount of contraction ; but the fact
that, in anaesthesia of the mucous membrane covering the vocal cords
produced by cocaine, the voice is not at all impaired, shows that mus-
cular contractions of extreme nicety can be carried on without any
such aid.
Sensations of Hunger and Thirst. — These are representatives of
the group of interior sensations. As Tiedemann pointed out long
CUTANEOUS AND INTERNAL SENSATIONS 1097
ago, at least two elements are involved in the somewhat vague
sensation of hunger : the local sensation of emptiness in the stomach,
and the general sensations of malaise, depression, and weakness.
There is some evidence that the general sensations are — in part at,
least — dependent upon the state of the stomach. But it would
appear that — at any rate, during prolonged deprivation of food — a
general condition of the tissues may exist which can arouse in con-
sciousness the sensation of hunger, even after the stomach has been
amply filled. Thus a patient with a fistula in the upper part of
the small intestine constantly suffered from hunger in spite of the
enormous quantities of food consumed. The stomach always felt
full, but as most of the food escaped from the fistula, the tissues
continued to be starved, and the general sensation of hunger re-
mained (Hertz). In diabetes the same thing may be observed.
On the other hand, it was noted by Carlson and one of his pupils
that after a fast of five days practically all of the mental depression
and some of the feeling of weakness disappeared during the first
meal. He therefore concluded that the depression of the central
nervous system was essentially a reflex condition, depending prob-
ably on afferent impulses from the digestive tract, rather than a
result of deficiency of nutrient material in the blood. Complete
recovery from the bodily weakness, however, did not take place
till the second or third day after breaking the fast.
Fig. 472. — Commencement of Gastric Hunger Contractions (the Large Elevations
in a Man. At x she belt was tightened and the hunger contractions inhibited.
To be read from left to right (Carlson and Lewis).
An important factor in the local sensations associated with
hunger is the strong periodical contractions of the empty stomach,
which have been shown to coincide with the hunger pains (Cannon
and Washburn).
Carlson was able in observations on a man with a permanent
gastric fistula to confirm this coincidence Even when the empty
stomach was artificially caused to contract by distending it with a
I09& THE SENSES
balloon, the man experienced a typical hunger pain. During his
own five days' fast Carlson recorded these contractions by means
of a small balloon attached to a rubber tube, which was swallowed
and allowed to remain in the stomach. The tube was connected
to a recording apparatus. It was found possible to go to sleep
with the balloon in the stomach, and to obtain a record all through
ii. .!:.»
j ; I I S f, I) H I I
III I
Fig. 473. — Gastric Hunger Contractions in a Man at a More Advanced and Intense
Stage than in Fig. 472. Tightening of the belt at x did not stop the con-
tractions which ran the usual course to their termination. To be read from
left to right (Carlson and Lewis).
the night. After the first day of starvation the hunger sensation
referred to the epigastrium was almost continuous, and did not
wholly disappear during the intervals between the periods of
vigorous gastric contractions. This feeble continuous hunger sen-
sation was obviously associated with the increased tonus and the
more or less continuous, although weak, rhythmical contractions
that correspond to the periods of relative quiescence of the empty
stomach during prolonged starvation. The precise manner in which
the hunger contractions of the stomach arouse the pangs or pains
of hunger remains in doubt. Since the sensation has a specific
character, it is to be supposed that it is subserved by a special
sensory apparatus with receptors in the stomach. The vagi do not
seem to be concerned. But the gastric contractions during digestion of
a meal notoriously do not cause such sensations, and therefore it has
been suggested that the nervous mechanism associated with the
local sensation of hunger becomes more and more excitable in the
absence of food, until at last the threshold is reached at which the
stimulus connected with the hunger contractions becomes effective.
It comes to the same thing to say that the presence of food in some
way inhibits the discharge which leads to the sensation. This,
CUTANEOUS AND INTERNAL SENSATIONS 1099
however, is only another way of saying that the true explanation is
still to seek.
Carlson was unable to confirm the common statement that
hunger disappears after the third day of starvation, although there
was certainly some decrease in the sensation of hunger, and especi-
ally in appetite, on the fourth and fifth days. As has been often
shown, the deprivation of food for long periods, or even till death,
when water is allowed, is not associated with acute suffering.
Appetite is distinguished from hunger by those observers who
have studied the question most precisely, but of the physiological
basis of the sensations that constitute appetite we know even less
than we do of the physiological basis of hunger. The taking of
food blunts the appetite, as it stills hunger. Fasting evokes both.
Yet during a prolonged fast, appetite, the desire for food and the
pleasure in the thought or at the sight of it, may disappear, or be
much lessened, while the hunger pangs are still sharp. The smell
and taste of agreeable food and the mental representations of these
sensations are elements in appetite, and even the associations con-
nected with the time and place of a customary meal and with those
who share it. But there is a gastric element as well: the mere
filling of the stomach apart from the passage of nutrient material
into the blood helps to satisfy the appetite; the emptying of the
stomach in the course of digestion seems of itself to take a part in
restoring the appetite for the next meal. To what extent, if at all,
the gastric element in the sensation of appetite is dependent upon
the same mechanism as the gastric element in hunger is unknown.
Some have supposed that the same stimulation which, when its inten-
sity is sufficiently increased, causes gastric hunger pains, causes in smaller
intensity a milder hunger sensation, which is the gastric factor in
appetite. According to Carlson, a factor in appetite is the memory
process of removal of hunger pangs by feeding, and he assumes that
the revival of such memories in consciousness depends upon the con-
dition of the alimentary canal, and is inhibited when the stream of
afferent impulses from the viscera is altered by changes in the motility
or secretory activity of the gastro-intestinal tract. He believes that
the secretion of the so-called appetite gastric juice, in man at least,
although clearly demonstrated on a case of gastric fistula during
mastication of palatable food, does not possess the great importance
attributed to it by Pawlow (p. 404), since normally there is a continuous
secretion of gastric juice in the absence of food in the stomach and of
psychical stimulation, and this is sufficient to initiate gastric digestion,
and therefore to insure a sufficient gastric secretion. The vagi do not
seem to contain fibres concerned in the sensations of hunger or appetite.
After section of these nerves, dogs, when they survive some time, eat
ravenously, although the food is often regurgitated.
Thirst.— This is a sensation, referred chiefly to the pharynx, and
certain of the sensory nerve fibres of this region, supplied by the
1 1 oo THE SENSES
glosso-pharyngeal nerve, may be assumed to be specifically related
to it. Under ordinary conditions the sensation is elicited through
the afferent nerves of the pharynx when the mucous membrane
becomes dry, as when dry or salt food is eaten, or dry and dusty
air inhaled, and local moistening of the area in question gives
temporary relief, even when no water is swallowed. When water
is long withheld, the water-content of all the tissues sinks, and a
more intense and distressing thirst, which cannot be allayed in any
way except by the ingestion of water, ensues. Probably in this
case afferent impulses originating in many organs, and conditioned
in some way by the abnormally low water-content of the blood and
tissues, as well as a more direct action of the loss of water upon the
(unknown) centre in which the sensation is represented, are re-
sponsible.
Relation of Stimulus to Sensation. — It is impossible to measure
sensation in terms of stimulus. All that we can do is to compare
differences in the intensity of stimuli and differences in the resultant
sensations, or, in other words, to compare stimuli together and to com-
pare sensations together. And when we determine the amount by
which a given stimulus must be increased or diminished in order that
there may be a just perceptible increase or diminution in the sensation,
it is found that (with certain limitations) the two are connected by a
simple law: Whatever the absolute strength of a stimulus of given kind
may be, it must be increased by the same fraction of its amount in order
that a difference in the sensation may be perceived (sometimes called
Weber's law). Thus, a light of the strength of one standard candle
must be increased by T^0th candle, a light of 10 candles by ^§Q, and in
light of 100 candles by a candle, in order that the eye may perceive
that an increase has taken place, just as the weight necessary to turn
a balance increases with the amount already in the pans. The fraction
varies for the different senses. It is about ^^ for light, £ for sound.
But it would appear that Weber's law does not hold for the pressure
sense, nor for the other senses above and below certain limits. Fechner,
making various assumptions, has thrown Weber's law into the form
y=k - — t where y is the intensity of sensation, x the intensity of
•*o
stimulation, x0 the smallest intensity of stimulus which can be perceived
(liminal intensity), and k, a constant. This so-called psycho-physical
law of Fechner states that the sensation varies as the logarithm of the
stimulus. But Fechner's law has been subjected to serious criticism,
and the subject cannot be further pursued here.
PRACTICAL EXERCISES 1101
PRACTICAL EXERCISES ON CHAPTER XVIII.
VISION.
I. Dissection of the Eye. — The student may profitably refresh his
memory on the anatomy of the eye by dissecting a fresh eye — that of
a large animal like an ox is preferable, but the eye of a sheep or dog
may also be used. The eye is removed from the orbit by cutting
through the conjunctiva where it is reflected on to the eyelids, care-
fully severing the extrinsic muscles and scooping the eyeball out of the
mass of loose connective tissue and fat in which it is embedded, and
which serves as a cushion to protect it from injury during its move-
ments. Observe the transparent cornea in front, blending at its pos-
terior border with the opaque sclerotic, which is covered by a layer of
conjunctiva reflected from the lids. On clearing the fat cautiously
away, the tendinous insertions of the external or extrinsic muscles of
the eyeball into the anterior part of the sclerotic will be seen. Identify
the various muscles (p. 1063).
Immerse the eye in water in a small glass dish, with the cornea
uppermost. The interior can now be seen, because the refractive
index of the cornea being nearly the same as that of water, the light is
only very slightly refracted there. The same effect is produced when
a cover-slip is placed over the cornea in the air ; a plane surface being
substituted for the curved anterior surface of the cornea, its refraction
is abolished. Observe in the fund us of the eye the optic disc, eccentric-
ally placed in the retina, and the retinal vessels radiating out from it.
A portion of the fundus shows brilliant iridescent colours in many
animals (the tapetum lucidum). This portion is abruptly bounded by
a line a little above the optic disc. The appearance is due to a peculiar
arrangement of the connective-tissue (including elastic) fibres in this
part of the choroid.
Pinch up with forceps a small portion of the sclerotic a little posterior
to its junction with the cornea, and clip it away with fine, blunt-
pointed scissors, being careful not to penetrate the choroid layer, which
lies immediately beneath the sclerotic. Extend the incision through
the sclerotic backwards, and then transversely, and peel off strips of
the sclerotic from behind forwards. The lower surface of the sclerotic
(the so-called lamina fusca) is dark, owing to the presence in it of the
same pigment which is so abundant in the choroid coat. Go on re-
moving the sclerotic piecemeal until a considerable area of the dark
choroid layer is exposed with the ciliary nerves passing forward on its
surface towards the iris. One or other of the long ciliary arteries may
also be seen coursing between the sclerotic and choroid if the sclerotic
happens to have been removed at its position. On the anterior part of
the choroid may be observed some pale fibres passing backwards from
the corneo-sclerotic junction. They are the meridional fibres of the
ciliary muscle (p. 1022).
The eye being immersed in water, remove cautiously with the forceps
and scissors the portion of the choroid exposed. The retina is now seen
as a pale membrane, transparent when quite fresh, but becoming whitish
soon after death. Cut through sclerotic, choroid, and retina about half-
way round the eyeball, a little posterior to the corneo-sclerotic junction.
The vitreous humour will bulge out. Since its refractive index is
nearly the same as that of water, it is scarcely observed when im-
mersed, and the interior of the eye can be easily seen through it.
The optic disc can now be again studied, with the stump of the optic
H02 THE SENSES
nerve entering it and the retinal vessels piercing the disc. In the
centre of the retina is the yellow spot.
In the anterior portion of the eyeball note the crystalline lens, and
at its circumference the radiating folds of the choroid called the ciliary
processes. Closely covering the ciliary processes, the anterior border
of the retina forms the ora serrata, a plaited arrangement like an old-
time ruff.
Now complete the separation of the anterior and posterior portions
of the eyeball. Remove the vitreous humour, noting that it is attached
to the ciliary processes and the posterior surface of the capsule of the
lens by its enveloping membrane, the hyaloid membrane. With
scissors snip through the corneo -sclerotic junction at one point down
to the border of the lens, and observe the suspensory ligament passing
from the ciliary body chiefly towards the anterior surface of the lens,
where it blends with the lens capsule. Open the anterior chamber of
the eye by an incision through the cornea in front of its junction
with the sclerotic. It is filled with the clear, watery, aqueous humour.
Note the pigmented iris projecting in front of the lens.
Remove the sclerotic and cornea for some distance along their line
of junction, using gentle pressure with the edge of a fine knife to separate
the junction from the attached border of the iris. The ciliary muscle,
forming a pale, narrow ring around the eye at the corneo-sclerotic
junction will be thus exposed. Its external surface is closely adherent
to the sclerotic, and its internal blends with the ciliary body. The
circumference of the iris is attached at its anterior border. Posteriorly
it passes into the choroid.
Take out the lens and observe the curvature of its anterior and
posterior surfaces. Determine which has the greater curvature. In
the excised eye the lens will, of course, be in the condition of relaxed
accommodation .
2. Formation of Inverted Image on the Retina. — Fix the eye of an ox
or of a dog or rabbit, after careful removal of part of the posterior
surface of the sclerotic, in one end of a blackened tube, with the cornea
in front. A tube made by rolling up a piece of thick brown paper will
do. Place a candle in front of the eye. Look through the other end
of the tube, and observe the inverted image of the candle formed on
the retina. Move the candle until the image is as sharp as possible.
Now bring between the candle and the eye a concave lens. The image
becomes blurred, the candle must be put farther away to render it
distinct, and perhaps no position of the candle can be found which will
give a sharp image. If the lens is convex, the candle must be brought
nearer, and a sharp image can always be formed by bringing it near
enough. If both a convex and a concave glass be placed in front of
the eye, they will partially or wholly neutralize each other. Instead
of the candle a window may be looked at. If the eye of an albino
rabbit can be obtained, it is not necessary to remove a part of the
sclerotic.
3. Helmholtz's Phakoscope (Fig. 474). — This instrument is em-
ployed in studying the changes that take place in the curvature of the
lens during accommodation. It is to be used in a darkroom. A candle
is placed in front of the two prisms P, P'. The observer looks through
the hole B; the observed eye is placed at a hole opposite the hole A.
The candle or the observed eye is moved till the observer sees three
pairs of images, one pair, the brightest of all, reflected from the anterior
surface of the cornea; another, the largest of the three, but dim, re-
flected from the anterior surface of the lens; and a third pair, the
smallest of all, reflected from the posterior surface of the lens (Fig. 421,
PRACTICAL EXERCISES 1103
p. 1021). The last two pairs can, of course, only be seen within the pupil.
The observed eye is now focussed first for a distant object (it is enough
that the person should simply leave his eye at rest, or imagine he is
looking far away), and then for a near object (an ivory pin at A).
During accommodation for a near object no change takes place in the
size, brightness, or position of the first or third pair of images; there-
fore the cornea and the posterior surface of the lens are not altered.
The middle images become smaller, somewhat brighter, approach each
other, and also come nearer to the corneal images. This proves (a) that
the anterior surface of the lens undergoes a change ; (6) that the
change is increase of curvature (diminution of the radius of curvature),
for the virtual image reflected from a convex mirror is smaller the
smaller is its radius of curvature. (The third pair of images really
undergo a slight change, such
as would be caused by a small
increase in the curvature of
the posterior surface of the
lens ; but the student need
not attempt to make this
out.)
4. Schemer's Experiment. —
Two small holes are pricked
with a needle in a card, the
distance between them being
less than the diameter of the
Fig. 474.— Phakoscope. pupil. The card is nailed on
a wooden holder, and a needle
stuck into a piece of wood is looked at with one eye through the holes.
When the eye is accommodated for the needle, it appears single; when
it is accommodated for a more distant object, or not accommodated at
all, the needle appears double. The two images approach each other
when the needle is moved away from the eye, and separate out from
each other when it is moved towards the eye. When the eye is ac-
commodated for a point nearer than the needle, the image is also
double; the images approach each other when the needle is brought
closer to the eye, and move away from each other when it is moved
away from the eye. If while the needle is in focus one of the holes be
stopped by the finger, the image is not affected. When the eye is
focussed for a greater distance than that of the needle, stopping one
of the holes causes the image on the other side of the field of vision
to disappear; if the eye is focussed for a smaller distance, the image
on the same side as the blocked hole disappears (Fig. 475). To de-
termine the near-point of distinct vision (p. 1029) the card may be
mounted vertically on a cork, and this fastened by a rubber band to
the end of a foot-rule. Move a needle, also inserted vertically into a
cork, along the rule, beginning at the end farthest from the eye, until
with the strongest effort of accommodation it is seen double. Then
push it back slightly to the point at which, again with maximum
accommodation, it is just seen single. Repeat the measurement with
a needle mounted horizontally. If regular astigmatism is present,
the distances will not be the same. Most eyes have slight regular
astigmatism.
In myopic persons the far-point of distinct vision can also be de-
termined by Schemer's experiment. The needle being left on a shelf
at the level of the eye, the person walks away from it backwards, re-
garding it all the time through the perforated card, till it is no longer
seen single.
1104
TfiE SENSES
5. Ktihne's Artificial Eye. — This is an elongated box provided with
a glass le;\s to represent the crystalline, and a ground-glass plate to
represent the retina. The box is filled with water to which a little
eosin has been added. The water must be perfectly clear. If the
tap-water is turbid it should be filtered or allowed to settle, or dis-
tilled water should be used. A beam of sunlight or electric light, or,
in case these are not available, a beam from an oil stereopticon, is made
to pass through the box. Many of the facts of vision can be illustrated
by means of this piece of apparatus. The modification of it introduced
by Lyon is very convenient.
(a) Let the rays of light pass through an arrow-shaped slit in a piece
of cardboard. An inverted image of the arrow is formed on the retina.
Move the retina nearer to or farther from the lens to make the image
sharp. In the eye of man and of most animals, accommodation is
not brought about by a change in the distance of retina and lens, but
by a change of curvature in the lens.
(6) Remove the lens. The focus is now far behind the retina. This
illustrates the state of matters after the lens has been removed for
cataract. The arrow
can again be sharply
focussed on the retina
by putting a convex
lens in front of the
artificial eye. But
this must be much
weaker than the lens
which has been re-
moved, for if the
latter be placed in
front of the eye, the
image is formed a
little behind the
cornea.
(c) Replace the lens.
Move the retina so
far back that the
image is focussed in
front of it. This is
the condition in the
myopic eye. Put a
weak concave lens in
front of the eye ; the image now falls more nearly on the retina. Move
the retina forward so that the focus is behind it. This corresponds
to the hypermetropic eye. Put a weak convex lens in front of the
eye to correct the defect.
(d) Observe that a plate with a hole in it, placed in front of the eye,
renders an indistinctly focussed image somewhat sharper by cutting
off the more divergent peripheral rays.
(e) Fill with water the chamber in front of the curved glass that repre-
sents the cornea. The focus is now behind the back of the eye alto-
gether. Refraction by the cornea is here abolished, as is the case in
vision under water. An additional lens inside the eye, or a weaker
one in front of it, corrects the defect. Fishes have a much more nearly
spherical lens than land animals, and a flat cornea.
(/) Fill the hollow cylindrical lens with water, and place it in front of
the artificial eye. The eye is now astigmatic. A point of light is
focussed on the retina, not as a point, but as a line. The vertical and
Fig. 475. — Schemer's Experiment. In the lower figure
the eye is focussed for a point farther away than the
needle, in the upper for a nearer point. The con-
tinuous lines represent ray's from the needle, the inter-
rupted lines rays from the point in focus.
PRACTICAL EXERCISES
1105
1IL v*******^*
in LII<= r' fitmre showing a number
^ . .
marked,
convenien
the Ophthalwometer. -— A
P^V/^nwninFigs. 476
Snined; H. ^S'tafe of ?SS
ated discs on which.r7"ri°us meri
ture of the
Hind.
until ^ XerTnd equally distinct
close together an a 4 | 4?7( d)
Rotate the o^rer\^n lines of the
until ^ long c^er^anne ^^
illuminated mires. or spurs ol 1 the ^a|nd the adjust-
But if the e^ is aff^r'e made to coincide so '^^ between
rotating A, the/h°_d the graduation is rea,^er^e between the two
a?e t oSry astigmatism.
iio6
THE SENSES
7. Spherical Aberration. — Close one eye, and bring a small object
(a pin or the point of a pencil) towards the other eye till it becomes
blurred. Interpose between the object and the eye a card perforated
by a small hole. The object becomes more distinct owing to the
cutting off of the peripheral rays (p. 1027),
8. Chromatic Aberration. — Look at Fig. 424 (p. 1028) from a distance
too small for perfect accommodation, and verify the facts given in
the description of the figure.
Fig. 477. — Vertical Section of Ophthalmometer. d, outer tube of the telescope
rotating in sleeve or collar s (supported by standard I, which is swivelled in
tubular support, g) ; k, diaphragm ; 10, eye-piece with lenses a and b ; n, a station-
ary disc, borne on collar s, graduated to indicate angle of rotation of u, a black
concave disc rotating with tube d, and having fixed in it two illuminated figures
(or mires), w, w, whose images reflected from the cornea are observed ; i is a pointer
carried on the tube d which shows on the graduated arc the amount of rotation;
12, 12, hemispherical shells containing small incandescent lamps for illuminating
the translucent mires. The lamps are connected with wires running in the
hollow stem t ; /is the inner tube of the telescope carrying the double prism, h, h.
By means of the rack o, projecting through the slot m, and engaged by the pinion
p, f is moved back and forth in the outer tube, thus approximating or separating
the corneal images of the mires. On the axis of p is a milled head for turning it,
and two duplicate discs graduated with a scale showing the radii of curvature
of the cornea in millimetres, and another scale showing their equivalent in
diopters.
$. Measurement of the Extent of the Field of Vision. — Use the peri-
meter shown in Fig. 449 (p. 1058).
(i) For White Light. — Fix in the holder, Ob, on the graduated arc,
a small piece of white paper, and put one of the charts supplied with
the instrument at the back of the wheel which revolves with the arc.
The observations can be recorded on this chart. The patient rests his
chin on K and adjusts one eye against O. This eye is kept fixed on
the mark at /during the whole period of observation, and the other eye
PRACTICAL EXERCISES
1107
Fig. 479-
Fig- 478J • i r>lane being moved to
eve, the other being
Led, and move over
a pencil
c
the
paper, 'until ^- ~— _
fust disappears. Make
a mark on the pape
atthispoint.andrepeat
?he observation for all
diameters of the field.
?hf blind spot is thus
marked -^Ficr- A8°^'
—-•
uoS THE SENSES
(2) Keep the eye closed for a short time. Then direct it to a surface
illuminated by a weak blue light. A dark blue or almost black spot
(Maxwell's spot), corresponding to the macula, is seen in the visual
field, owing to the absorption of the blue rays.
Fig. 481, — Composite picture of Blind Spot (not reduced). The blind spot of the
right eye was mapped by 31 men, the eye being always at a distance of 12 inches
from the paper. The maps were then superposed. The amount of white at
any point of the figure is intended to correspond to the number of maps which
overlapped at that point. Although the mechanical process of reproduction
gives rather an imperfect view of the composite map, the area in the centre of
the figure where the white is most continuous, and which represents the shape
of the majority of the blind spots, evidently bears a general resemblance to the
outline in Fig. 480.
12. Ophthalmoscope — (i) Human Eye (p. 1031). — Let A be the ob-
server, and B the person whose eye is to be examined. A and B
are seated facing each other. Suppose that the right eye of B is to
be examined. Close to the left ear of B is a lamp on a level with his
eyes : the room is otherwise dark. For a clinical examination, the pupil
should be dilated by putting into the eye a drop of a 0-5 per cent.
1 109
EXERCISES
or the
tut* We? on B-s temple. ^ .^ ffiethod.
IIIO
THE SENSES
of it, minus one diopter, the refraction can be estimated. Suppose,
for instance, that a convex lens of two diopters is required, then hyper-
metropia of one diopter exists.
In order to facilitate the introduction of the various lenses, instru-
H
15 17
27
Fig. 482. — Geneva Retinoscope and Ophthalmoscope. A, frame of instrument;
B, retinoscope attachment; C, ophthalmoscope attachment; D, base; i, mirror
handle; z, clip to hold the proper lens to correct the abnormality of refraction
of observer or patient when viewing the retina with the ophthalmoscope; 3, scale
indicating the meridian of handle and pointer ; 4, ring in which mirror cup rotates ;
6, mirror; 7, mirror spring for reflecting the light to a given point; 8, screws for
adjusting mirror; 9, screw for holding light and ring 4 in position; 10, handle
for swinging A from side to side; 13, opening in iris diaphragm, controlled by
handle 14; 15, lamp hood; 17, knurled handle for rotating disc containing the
full diopter lenses; 18, handle for rotating the disc containing the fractional
lenses (white numbers indicate plus lenses, and red minus lenses) ; 20, opening
through which observer looks when adjusting the retinoscope to the patient's
eye; 21, pinion for advancing or retracting instrument; 24, bracket ring of
retinoscope attachment B, which is slipped over ring 25 when putting retinoscope
attachment into place; 28, clips for ' fogging ' lenses through which the patient
looks to relax accommodation; 29, opening through which the pupil is viewed in
retinoscopy; 30, opening containing clip in which extra lenses may be inserted
when required, or the defect is over 8 diopters; 32, patient's eye-cup; 33, ring of
ophthalmoscope attachment C, which telescopes over 25; 34, ophthalmoscope
tube; 35, binding-screw which holds the instrument in a fixed position when
retinoscope is being used ; 37, rack to raise and lower the instrument ; 40, handle
controlling height of chin-rest 44; 46, forehead -rest.
ments called skiascopes or retinoscopes may be used, one of which is
shown in Fig. 482.
14. Pupillo-dilator and Constrictor Fibres. — (a) Set up an induction
machine arranged for tetanus, and connect a pair of electrodes through
PRACTICAL EXERCISES
glass, in your own eye, the
contract. hen the eye is accommodated tor a ^^ at
(c) Observe that when _ x ? when a distant oop ^ Qn
st -to-
of the rotating discs, ^y ^^ paper ^stened. o ^
produced, and any °^. hed by adding white to J^e three
thirty secondfthaefilament will appear dark^ or forty
r:
•"
' -
THE SENSES
of a millimetre. Set the card up in a good light, and walk backwards
from it till the individual lines just fail to be discriminated. Measure
the distance from the card at which this occurs, and calculate the size
of the retinal image (p. 1019).
19. Colour-Blindness. — Spread out Holmgren's coloured wools on
a sheet of white filter-paper in a good light. Do not mention the
colours of any of the wools, but (i) ask the person who is being tested
to pick out all the wools which seem to him to match a pale pure green
wool (neither yellow green nor blue green), which is handed to him.
He is not to make an exact match, but to pick out the skeins which
Fig. 483. — Apparatus for Colour-Mixing.
seem to have the same colour. If he makes any mistakes, by selecting,
e.g., in addition to the green skeins, any of the ' confusion colours,"
such as grey, greyish-yellow, or blue wools, there is some defect of
colour discrimination. To determine whether the person is red or green
blind, tests (z) and (3) are then made. (2) Give him a medium purple
(magenta) wool, and ask him to pick out matches for it. If he is red-
blind, he will select as matches to it only blues and violets, as well as
other purples. If he is green-blind, he will select only greens and
greys. (3.) The third test is a red wool. In selecting matches for this,
the red-blind will choose (with reds) greens, greys, or browns less bright
PRACTICAL EXERCISES
than the test. The green-blind will choose (with reds) greens, greys,
or browns which are brighter than the test.
It must be remembered that the results of tests with the coloured
wools need not be precisely the same as those with coloured lights,
and that when there is a discrepancy between the two the test with
the coloured lights should be accepted; for it is usually the normal
perception and discrimination of coloured lights which has practical
importance.
20. Talbot's Law. — Rotate a disc one sector of which is black and the
rest white, or a disc like that in Fig. 446 (p. 1050). A uniform shade is
produced as soon as a speed of about 25 revolutions a second has been
attained, and this is not altered by further increase in the speed.
21. Purkinje's Figures. — (a) Concentrate a beam of sunlight by a
lens on the sclerotic at a point as far as possible from the corneal margin,
passing the beam through a parallel-sided glass trough filled with a
solution of alum to sift out the long heat-rays. The eye is turned
towards a dark ground. The field of vision takes on a bronzed appear-
ance, and the retinal bloodvessels stand out on it as a dark network,
which appears to move in the same direction as the spot of light on the
sclerotic. A portion of the field corresponding to the yellow spot is
devoid of shadows (p. 1043).
(6) Direct the eyes to a dark ground while a flame held at the side of
the eye, and at a distance from the visual line, is moved slightly to and
fro. A picture of branching bloodvessels^appears. This experiment
is performed in a dark room.
(c) Immediately on awaking look at a white ceiling for an instant;
a pattern of branched bloodvessels is seen. If the eye be at once closed,
and then opened with a blinking movement, this may be observed again
and again. Ultimately the appearance fades away.
HEARING, TASTE, SMELL, TOUCH, ETC.
22. Monochord. — Study by means of the monochord, a stretched
string with a movable stop, the relation between the pitch of the nqte
given out by a vibrating string, and its length and tension.
23. Beats. — Cause two tuning-forks of nearly equal pitch to vibrate at
the same time. Make out the beats, and count their number per second.
24. Sympathetic Vibration. — Take three tuning-forks mounted on
resonators. Let two of them be of the same pitch. Strike one of
these; the other is thrown into sympathetic vibration, and continues
to give out a note after the first is quickly stopped by touching it.
The third fork is unaffected.
25. Determine by means of Galton's whistle the pitch of the highest
audible tone.
26. Cranial Conduction of Sound. — When a tuning-fork is held
between the teeth, a part of the sound passes out of the ear from the
vibrating membrana tympani; if one ear is closed, the sound is heard
better in this than in the open ear. If the tuning-fork is held between
the teeth, till, with both ears open, it becomes inaudible, it will be
heard for a short time if one or both ears be stopped ; and when in this
position the sound again becomes inappreciable.it can still be caught
if the handle be introduced into the auditory meatus.
27. Taste. — (i) Apply to the tongue by means of a camel's-hair
brush a solution of quinine (i to T.OOO), sodium chloride (i to 200),
cane-sugar (i to 50), and sulphuric acid (i to 1,000). Determine at
what part of the tongue the strongest sensations are elicited by each.
IH4
THE SENSES
(2) Prepare a series of solutions of sulphuric acid of gradually in-
M
creasing strength, beginning with a - '• — solution (a two-thousandth
gramme-molecular solution) (p. 426). Put into the mouth, after
previous rinsing with distilled water, 4 or 5 c.c. of one of the solutions
of the acid, beginning with the weakest, and determine at what con-
centration of the H ions the acid taste first appears, rinsing out the
mouth after each observation. Repeat the experiment with solutions
of hydrochloric acid, and determine whether the threshold value is the
same.
A similar comparison of the necessary concentration of the OH
ions can be made with solutions of sodium hydroxide and potassium
hydroxide.
(3) Connect two short pieces of platinum wire with the copper wire
from the poles of a Daniell or dry cell. Apply one platinum wire to
the inner surface of the lip and the other to the tip of the tongue.
Reverse the poles. Note the difference in the sensation according to
whether the anode or the kathode is on the tongue.
28. Smell. — (i) Pass a current through the olfactory mucous mem-
brane by connecting one electrode with the forehead and the other
by means of a small piece of sponge or cotton-wool soaked in physio-
logical salt solution with one nostril. An odour like that of phosphorus
will be perceived.
(2) To distinguish between Taste and Smell. — Use a solution of clove-
oil in water which can just be distinguished from water when it is placed
on the tongue by means of a camel's-hair brush. Close the nostrils,
and determine whether the clove-oil can now be detected.
29. Touch and Pressure. — (i) Prepare a number of hair aesthesio-
meters by fastening hairs of different thicknesses to small wooden
handles about 3 inches long by means of sealing-wax. Hairs as straight
as possible should be chosen, or straight portions of hairs. The hair is
to be fastened on one end of the piece of wood at right angles to the
long axis of the handle, so that about an inch of the hair projects to
one side. Determine the pressure value of each hair by pressing it
down upon the scale of a balance till it is slightly bent, and observing
the greatest weight in the other scale which it will lift. Mark the
number in milligrammes on the handle. In this way, when a hair is
placed at right angles to a point of the skin, and pressure exerted on
it till it begins to bend, the intensity of the touch stimulus — i.e., the
pressure exerted on the skin — is definitely measured, and by using
hairs of different pressure values the threshold value of the stimulus
for any touch area — i.e., the pressure which just gives the sensation
of light touch — can be determined (p. 1081).
(a) Using the back of the hand, note how light a touch of the aesthesi-
ometer applied to the end of a hair suffices to elicit a sensation of touch,
as compared with a part free from hairs. The hairs dimmish the
threshold of the stimulation by acting as levers, whose short arm
presses against the nerve-endings surrounding the hair-follicles, while
the stimulating weight acts on the long arm. When the skin is shaved
the threshold is always raised.
(6) Shave an area on the back of the hand, and make out the relation
of the touch-spots to the hair follicles. Each hair has an especially
sensitive touch-spot just on the ' windward ' side of the follicle (p. 1080).
Using sesthesiometers of different pressure values, determine the
threshold value for the shaved area. Outline an area of a square
centimetre on the skin, and determine the number of touch-spots,
using first a hair of the threshold value, and then going over the area
PRACTICAL EXERCISES 1115
again with a hair of a decidedly higher pressure value. The threshold
value for many parts of the hairy skin is obtained with a hair which
bends at 70 milligrammes. Repeat the determinations for other skin
areas, such as the back of the upper arm, the palm of the hand, the
anterior surface of the leg, the chest, the back, and the cheek, forehead,
and lips.
It is well that the subject should be blindfolded during the ex-
amination of the skin areas. He should understand by preliminary
practice what the sensation of light touch is, the perception of which
he is to indicate. With strong sesthesiometer hairs the pricking sen-
sation due to stimulation of pain-spots must be discriminated from
touch sensation. When the two sensations are elicited together, the
touch sensation is momentary, and the subject must be alert to detect
it immediately on stimulation. The pain sensation develops more
slowly, but lasts longer and becomes much more conspicuous than the
touch sensation, which accordingly is apt to be submerged by it in
consciousness.
(2) Touch the skin with a blunt point (at or about skin temperature).
With light contact the sensation is that of simple touch. On in-
creasing the pressure, the quite distinct sensation of deep pressure is
perceived.
(3) Touch a portion of skin with a camel's-hair brush of ordinary
size, pressing on it till the hairs of the brush begin to bend. The first
sensation of simple contact gives place to a sensation of pressure. Re-
peat with a camel's-hair brush of the finest hairs half a centimetre in
length, cut away till its cross section is only half a millimetre in diameter
at the base. Probably a pure sensation of touch, without any pressure
element, will be obtained when the brush is applied so as just to bend
the hairs.
(4) Find the least distance apart at which the points of the aesthesi-
ometer compasses can be recognized as two when applied to the back of
the hand, the forearm, upper arm, forehead, finger-tips, or tip of the
tongue. Both points of the compasses must be placed on the skin
at the same time, and the same pressure applied to both. The subject
must not see the points.
(5) Time Discrimination of Touch. — Touch the prong of a vibrating
tuning-fork lightly with the. tip of the finger. The taps of the prong
on the skin do not blend into a continuous sensation even when the
fork vibrates several hundred times per second.
30. Temperature Sensations. — For the investigation of these, pieces
of thick copper wire, filed at one end to a blunt point, and fixed by
the other in a small wooden handle, may be used. They can be heated
in a sand-bath or in a beaker of water to the desired temperature, or
cooled in cold water or in ice. Or a metal tube drawn out at one end,
through which water at the required temperature can be passed before
use, may be employed. Another device is a metal cylinder ending in
a point, and filled with water at the given temperature.
(i) On the dorsal side of the hand outline an area of skin with a
pen or a coloured pencil. Divide this into areas of 4 square milli-
metres. Go over the area with a wire or cylinder at a temperature of
about 40° C., and determine the extent and position of the spots which
on contact yield a sensation of warmth, marking them on the skin by
ink-dots, or mapping them on ruled paper. Then repeat the ex-
ploration with points at a temperature of about 15° C., and map the
spots which yield a sensation of coolness. Now note whether a warm
spot touched with a point at 15° C., or a cold spot touched with a point
at 40° C., yields any temperature sensation.
i "6 THE SENSES
(2) Touch the skin with a test-tube containing water at 50° C.( and
again with a test-tube containing ice. Do the sensations differ in any
way from those of pure warmth and coolness ? Repeat (i) with
temperatures of 50° and o°, and note whether there is any difference
in the quality of the sensations yielded by the warm and cold spots.
When a cold spot is touched with a point at a temperature of 50°, or
a warm spot with a point at a temperature of o°, is any sensation
obtained ? If so, what ?
(3) Apply successively to one and the same portion of the skin test-
tubes containing water at 50°, 45°, 40°, 35°, 30°, 25°, 20°, 15°, 10°,
5°, and o° (ice), and determine the sensations excited in each case.
The contact should only be momentary, so as not to cause extensive
and lasting change of temperature of the skin. Note that there is a
certain range of temperature above and below that of the skin within
which no sensation of heat or cold is given.
(4) Take three beakers of water at 20°, 30°, and 40° C. respectively.
Place a finger of one hand in the coldest beaker, a finger of the other
hand in the warmest, until no definite temperature sensations are felt
by either finger. Plunge both fingers into the beaker at 30° C.( and
temperature sensations will be perceived.
(5) Temperature Discrimination. — Find the least perceptible differ-
ence in temperature between two beakers of water at about o° C.
Repeat the experiment with two beakers of water at about 30° C., and
again with two beakers of water at about 55° C. Use the same hand.
Expose the same amount of surface to the water.
(6) Compare the acuteness of the temperature sensations of the
skin and the mucous membrane of the mouth, touching a given portion
of skin and then a portion of mucous membrane with tubes containing
water at various temperatures.
31. Pain. — (i) Using a pin, explore a cutaneous area to determine
whether every point of the skin yields the painful sensation of pricking.
Especially compare the result of stimulating the region in the imme-
diate neighbourhood of the hairs with the spaces between hairs. Dis-
criminate the touch sensation given by the light contact of the pin-point
from the painful impression caused when the pressure is increased.
Note that the touch element is more evanescent than the pain element.
(2) With strong v. Frey hairs determine the pressure at which the
sensation of touch passes into that of pain.
(3) Compare the sensibility to pin-pricks of the mucous membrane
within the mouth with that of the skin.
32. Having determined the systolic blood-pressure in one arm of
a fellow-student (p. 113), release the pressure in the cuff, then raise
the hand in the air so as to empty the arm of blood, and while it
is still raised, get up a pressure in the cuff equal to the systolic pressure.
Lower the hand and maintain this pressure by squeezing the bulb occa-
sionally. Be careful not to increase the pressure above the systolic
pressure. There is no disadvantage in letting it drop 5 to 10 milli-
metres below systolic pressure from time to time. Now compare the
acuity of the sensations of contact, pressure, warmth, cold, and pain
in the anaemic and the normal hand, always on symmetrically placed
areas of the two hands. Repeat the comparison at intervals till a
definite difference is found, and note the sensation for which the acuity
first diminishes. Do not prolong the experiment unduly. If the sub-
ject experiences discomfort, the pressure in the armlet is to be at once
released.
CHAPTER XIX
REPRODUCTION
Regeneration of Tissues. — In lower forms of animals and in all
or most plants, the power of regeneration is much greater than in
the higher animals and in man. A newt can reproduce an am-
putated toe, and every tissue — skin, muscle, nerves, bone — will be in
its place. After extraction of the crystalline lens in triton larvae,
a new lens is formed from the iris epithelium. Artificial mouths
surrounded by tentacles can be formedjn Cerianthus, an animal
belonging to the same group as the sea-anemonss, merely by
making a cut in the body-wall and preventing it from closing. In
an Ascidian, too (Cynone intestinalis), artificial openings in the
bianchial sac, surrounded by numerous pigmented points similar
to the eye-spots around the natural mouth and anus, have been
produced (Loeb). A classical example of regeneration in inverte-
brates is that of the rays of starfishes after amputation. According
to some observers, this massive regeneration, as well as other in-
stances of the regeneration of complicated organs in invertebrates,
depends, in some degree at any rate, upon the nervous system.
Even in the higher animals regeneration of tissues is a common
phenomenon. Since cells are constantly dying within the body,
they must be constantly reproduced. In some tissues the process
by which this is accomplished is more evident, and therefore better
known, than in others. The most highly-organized tissues are
with difficulty repaired, or not at all. The epidermis is always
wearing away at its surface, and is being constantly replaced by the
multiplication of the cells of the stratum Malpighii. In the corneous
layer we have only dead cells; in the Malpighian layer we have every
histological gradation from squames to columns, and every physio-
logical gradation from cells which are about to die to cells that have
just been born. The corpuscles of the blood undoubtedly arise at
first, and are recruited throughout life, by the proliferation of
mother-cells. The gravid uterus grows by the formation of new
fibres from the old, and by the enlargement of both old and new.
A severed muscle is generally united only by connective or scar
tissue, but under favourable conditions a complete muscular
1117
ni8 -'REPRODUCTION
' splice ' may be formed. A broken bone is regenerated by the
proliferation of cells of the periosteum, which become bone-
corpuscles. Gland cells — e.g., liver cells^are also, under certain
circumstances, capable of regeneration. Some of the most striking
instances of new formation of glandular tissues have already been
mentioned in connection with the growth of grafts of certain of the
endocrine organs (e.g., thyroid, adrenal cortex), when a physio-
logical insufficiency has been created by removal of the greater
portion of the organ (p. 648) . There is no evidence that the influence
of the nervous system is a factor. It is doubtful whether there is any
new formation of nerve-cells in the adult organism, but peripheral
nerve-fibres which have been destroyed by accident or operation
are readily regenerated, and the end-organs of efferent nerves may
share in this regeneration.
Thus, in a sense, reproduction is constantly going on within the
bodies even of the higher animals. But since the whole organism
eventually dies, as well as its constituent cells, a reproduction of the
whole, a regeneration en masse, is required.
A cell of the stratum Malpighii can only, so far as we know,
reproduce a similar cell, and this is characteristic of cells that have
undergone -a certain amount of differentiation, especially in the
higher animals. The fertilized ovum, on the other hand, has the
power of reproducing not only ova like itself, but the counterparts
of every cell in the body. And this is only the highest development
of a power which is in a smaller degree inherent in other cells in
lower forms. Plants and the lowest animals are far le^s dependent
upon reproduction by means of special cells. A piece of a Hydra
separated off artificially or by simple fission becomes a complete
Hydra, as was shown by Trembley a century and a half ago. A
cutting from a branch, a root, a tuber, or even a leaf of a plant, may
reproduce the whole plant. It is as if each cell in these lowly forms
carried within it the plan of the complete organism, from which it
built up the perfect plant or animal. -
Reproduction in the Higher Animals. — In regard to the secretions
of the reproductive glands, all that is necessary to be said here is
that, unlike other secretions, their essential constituents are living
cells. The spermatozoa in the male have, indeed, diverged far from
the primitive type. Certain cells (spermocytes) in the tubules of the
testicle divide, each forming two daughter spermocytes. Each of
the daughter spermocytes in turn divides, so that four cells (sperma-
tids) are formed from each spermocyte. In the final division which
produces the spermatids a reduction of the chromosomes (p. 1122)
occurs, so that the spermatid possesses only one-half the number
characteristic of the somatic cells of the species. The spermatids
elongate and become spermatozoa, the head of the latter repre-
senting the nucleus of the former; and it is this nucleus (with the
REPRODUCTION IN THE HIGHER ANIMALS 1119
middle piece originally containing the male centrosome and attrac-
tion sphere, p. 5) which is the essential contribution of the male to the
reproductive process. The tail of the spermatozoon is simply, from
the physiological point of view, a motile arrangement, whose function
it is to carry the nucleus of the male element, freighted with all that
the father can transmit to the offspring, into the neighbourhood of
the female reproductive element or ovum. After the spermatozoon
has penetrated the ovum its tail disappears, being probably
absorbed. The function of the accessory reproductive glands, the
prostate, the seminal vesicles, and Cowper's gland, are not well
understood. But the spermatozoa in the act of ejaculation are
mixed with the secretions of these glands, and therefore it is to be
supposed that they are of importance. When the prostate and the
seminal vesicles are removed in white rats, the female is no longer
fertilized, although the sexual power of the male is unaltered. The
testes apparently develop spermatozoa in the normal manner, but
for some reason they either do reach the ovum or do not react
with it normally if they do reach it. When the testes are re-
moved from a young animal, the development of the prostate is
interfered with; in an adult animal the gland atrophies.
The ovum also begins as a typical cell with nucleus (germinal
vesicle), nucleolus (germinal spot), centrosome and attraction sphere,
and it forms, by its repeated subdivision, all the cells of the fcetal
body. But, except in some (parthenogenetio) forms, it never
awakens to this reproductive activity till fecundation has occurred;
and fecundation essentially consists in the union of the mab with the
female element, or rather in the union of the male and female nuclei.
From time to time a ripe Graafian follicle, overdistended by its
liquor folliculi, bursts on the surface of the ovary and discharges an
ovum. It is probable that in the majority of mammals (e.g., the
cow, mare, sow, sheep, and bitch) ovulation, or the discharge of
the ovum, occurs spontaneously during oestrus (period of heat).
In others (e.g., the rabbit, ferret, and cat), it seems only to take place
as a result of copulation. Whether sexual intercourse has any in-
fluence upon ovulation in women can hardly be considered as settled.
The common opinion is that most ova are discharged spontaneously
at the time of the menstrual period, but some writers take the view
that the discharge bears no relation to menstruation. Only one
ovum seems to be shed each month. It was foimerly believed that
the frayed or fimbriated end of the Fallopian tube, rising up finger-
like from the dilatation of its bloodvessels, grasps the ovum. But
it is more than doubtful whether this occurs. It is more probable
that the ovum is first discharged into the pelvic cavity, and
is guided to the orifice of the Fallopian tube, not necessarily
that of its own side, by the movements of the cilia around the
orifice, and then passed slowly along the tube by the downward
1 120 REPRODUCTION
lashing cilia which line it. Probably the ovum takes as a rule eight
or ten days to reach the uterus, and it is during this time that
fertilization takes place. If not impregnated, it soon perishes amid
the secretions of the uterus — how soon has been matter of discussion,
and can hardly be considered as settled. If, however, impregnation
occurs, the ovum penetrating the superficial epithelium into the
subepithelial connective tissue becomes fixed in one of the crypts or
pouches of the uterine mucous membrane (cLecid.ua serotina), which
grows round it as the decidua reflexa. The Graafian follicle, after
the discharge of the ovum, fills up with blood, and a cellular struc-
ture, the corpus luteum, is developed in its interior from cells in
the wall of the follicle. In the absence of impregnation the corpus
luteum begins to disappear before the next menstrual period, and is
spoken of as a false corpus luteum. But when pregnancy occurs, it
continues to grow till the fourth or fifth month of pregnancy, and is
called a true corpus luteum.
Menstruation. — In the mature female, from puberty, the age at
which the reproductive power begins (thirteenth to fifteenth year),
on till the time of the menopause (fortieth to fiftieth year) , at which
it ceases, an ovum — or it may be in some cases more than one — is
discharged at regular intervals of about four weeks. This discharge
is accompanied by certain constitutional symptoms and local signs
that last for a variable number of days. The temperature of the
body diminishes somewhat, rarely more th.in i° F., and there is
also a slight fall in the pulse-rate. The genit;i I organs are congested,
and a quantity of blood, which varies in different individuals, but
is usually not over 50 c.c., is shed. If more than 60 c.c. is lost, the
flow is copious. Over 100 c.c. it is abnormally great (G. Hoppe-
Seyler). At the same time, the whole or a portion of the mucous
membrane of the uterus is cast off.
As to the physiological meaning of this menstruation, as it is
called, opinion is divided. Two chief theories have been proposed
to account for it, both of which agree in considering the phenomenon
to be connected with a preparation of the uterus for the reception
of the ovum. But according to the theory of Pfliiger, the mucous
membrane is stripped off (by a process analogous to the ' f eshening '
or paring of the indurated edges of a wound by the surgeon, in
order that union may occur when they are brought together) on
the chance, so to speak, that an impregnated ovum may arrive. On the
alternative theory, this change takes place because the ovum has not
been impregnated, and the bed prepared for it not being required,
the swollen and congested uterine mucous membrane undergoes
degeneration, and is in part cast off (Reichert, Williams, etc.).
However this may be, it is now pretty generally agreed that the
degenerative process involves only the superficial portion of the
mucosa, and not its whole thickness.
MENSTRUATION
The process of menstruation, and the nutrition of the genital
organs, especially the uterus, are intimately dependent upon the
ovaries. There is good evidence that the influence is exerted through
an internal secretion formed by some portion of the ovarian sub-
stance. When, for instance, the ovaries of young animals (guinea-
pigs) are removed from their normal situation and transplanted to
a distant part of the body, the external genitals, vagina, and uterus
undergo the normal development instead of being arrested in their
growth, as is the case when the ovaries are removed altogether. The
removal of the ovaries in adult animals leads to fibrous degeneration
of uterus and Fallopian tubes. On the other hand, removal of the
i terus has no effect on the development of the ovaries in a young
animal, and does not cause degeneration of the ovaries of an adult
animal. In monkeys, in which a menstrual flow comparable to that
in the human female occurs, it was found that menstruation took
place after the ovaries had been transplanted from their original seat,
and the flow stopped when the transplanted ovaries were removed.
The view has been put forward that the important part of the ovary
for these functions is the corpus luteum, which is considered to be
a gland with an internal secretion (Born). This secretion seems
to be connected with the implantation of the ovum and the sub-
sequent growth of both ovum and uterus. According to Fraenkel,
the absence of the corpus luteum prevents implantation. The
experiments of Marshall and Jolly also indicate that the corpus
luteum forms some substance, which exerts an action on the uterine
mucosa, during the earlier stages of pregnancy. When the ovum
has not been fertilized the corpus luteum brings about menstruation.
Where fertilization has occurred it prepares the uterus for the im-
plantation of the ovum. It is generally considered that as regards
their origin there is no difference between the true and the false
corpora lutea.
The mode of origin of the corpus luteum has given rise to much
discussion. Two chief views have been put forward: (i) That it is
a structure derived from certain large epithelium-like cells (theca
cells) in the connective-tissue wall (theca) of the discharged follicle
(v. Baer, et al.} ; (2) that it is developed from the follicular epithelium
(membrana granulosa) (Sobotta, et al.). The first view seems to be
best established. The theca cells multiply and grow into the cavity
of the discharged follicle. Their yellowish colour is due to the
presence in them of lipoid droplets.
The influence of the ovary on the formation of the decidua has
been illustrated in a very interesting way by the investigations of
L. Loeb on the artificial production of deciduomata. He has shown
that if a number of incisions are made into the uterus of a rabbit or
guinea-pig within a certain interval after the cestral period (period of
heat), a structure with the histological characters of the decidua
7*
iI22 REPRODUCTION
develops at each wound. Impregnation does not appear to be a
necessary factor, nor even contact of the ovum with the uterine
mucous membrane. On the other hand, ovulation, the discharge of
an ovum or ova, or at any rate the condition of the ovary associated
with this discharge, seems to be indispensable. For extirpation of
the ovaries in a large number of guinea-pigs prevented the formation
of deciduomata from wounds of the uterus made at the most favour-
able period after copulation. The uterus then appears to have an
inherent power of responding to such a stimulus as a mechanical
injury by the production of a decidual structure, but only under the
influence of the ovary. The ovarian factor is probably not nervous
but chemical, some specific substance which acts on the uterus
being liberated periodically in connection with the sexual rhythm.
Development of the Ovum. — Before fecundation, and apparently
as a preparation for it, the ovum is the seat of remarkable changes,
similar upon the whole to those seen in the mitotic or indirect
division of ordinary cells. * They have been most fully studied in
the eggs of certain invertebrate animals.
The division of the cell is initiated by changes in the centrosome and
attraction sphere. The centrosome divides into two daughter centro-
somes. These take up a position one at each pole of the nucleus.
Each daughter centrosome is surrounded by a system of radiating lines
or filaments, which are less conspicuous than the chromatin filaments
of the nucleus, since they do not stain as these do. Meanwhile the
nuclear membrane and the nucleoli disappear, or at any rate become
indistinguishable from the rest of the chromatin skein. The skein
breaks up into chromosomes, the number of which is constant for a given
species, but is not the same in all species of animals.
The daughter centrosomes or astrospheres are united by meridional
achromatic fibres, which form a spindle running through the nucleus
from one pole to the other. The chromosomes arrange themselves at
right angles {equatorially) to the spindle, and then each chromosome
divides longitudinally into two. The halves of the chromosomes now
pass toward their respective centrosomes, being perhaps guided by the
fibres of the spindle. It results from this that two daughter nuclei are
formed, each with the same number of chromosomes as the original
nucleus, although with only half the amount of chromatin. The cyto-
plasm divides also, so that the parent cell is now represented by two
daughter cells. In ordinary cell division the two daughter cells are of
equal size, but in the division of the ovum which occurs before fertiliza-
tion the two resulting cells are very unequal. The large cell continues
to be known as the ovum; the small one is the first polar body. After
extrusion of the first polar body the ovum again divides unequally. A
new spindle forms, and a second polar body, again much the smaller of
the two daughter cells, is cast off. There is a difference, however,
between the process of division which gives rise to the first and that
which gives rise to the second polar body. In the case of the latter a
so-called reduction-division occurs; the chromosomes do not split longi-
tudinally, but half .of the original number pass into each daughter
nucleus. As to the significance of these changes there has been much
discussion. It is agreed that the result of the process is the expulsion
* For figures illustrating the changes, see any good textbook of Histology.
DEVELOPMENT OF THE OVUM 1123
of a portion of the chromatin, the ovum now possessing only half the
original number of chromosomes, although nearly all the original
cytoplasm. In fertilization the original number is restored by the male
element when it arrives and penetrates the ovum. For in the final cell
division by which the mature spermatozoon is formed the chromosomes
of its nucleus are also, after two divisions essentially similar to those
occurring in maturation of the ovum, reduced to half the normal number.
The two reduced nuclei in the fertilized ovum are spoken of as the
male and female pronuclei. By their union a single nucleus is formed
with the number of chromosomes normal to the species.
An enormous amount of interesting work has been done with the
view of illustrating the connection of the complicated phenomena
described with the structure of the ovum. Only a bare reference
to one or two of the experiments is possible here. Driesch and
Hertwig find that the nucleus can be made artificially to change its
place with reference to the yolk, without hindering the development
of a normal animal. Lillie has shown that centriiugalization of the
eggs of annelids, although it markedly alters the distribution of the
yolk and other substances, does not affect the form of cleavage.
The polar bodies appear in the position which they would normally
occupy. In other words, no redistribution of the granules or nucleus
affects the polarity of the egg, which therefore is a function or
property of the ground substance of the protoplasm. The whole
of the protoplasm, however, is not necessary for complete develop-
ment. Even in Amphioxus, the lowest of the vertebrates, the
eggs have been broken up by shaking, and a complete animal
evolved from as little as one-eighth of an ovum. If the separation
was incomplete a kind of Siamese twins, or even triplets, could be
obtained (Wilson and Mathews). Nor is it always indispensable
that both pronuclei should be present.
Parthenogenesis. — Attempts have been made to separate the
constituents of spermatozoa which are essential to fertilization.
From the sperm of a sea-urchin a substance can be extracted by
strongly hypotonic salt solutions, containing ether, which acts as a
powerful fertilizing, agglutinating, and cytolyzing agent upon the
eggs. It is soluble in dilute acid, and is probably identical with a
fertilizing agent called oocytase present in blood-serum (Robertson).
Whatever it is that the spermatozoon supplies, the process of
fertilization can in certain forms be started artificially in the absence
of spermatozoa or any of their constituents. The studies of Loeb
and his pupils on artificially induced parthenogenesis are of special
importance. When the unfertilized eggs of the sea-urchin are
exposed for one or two minutes to 50 c.c. of sea-water, to which
3 or 4 c.c. of decinormal acetic acid has been added, the majority of
the eggs form the membrane characteristic of the entrance of the
spermatozoon. When these eggs are afterwards exposed for thirty
to forty minutes to 100 c.c. of sea-water, to which 14 or 15 c.c. of a
strong solution of sodium chloride (two and a half times the strength
1124 REPRODUCTION
of a normal solution, or about 14-6 per cent.) has been added, those
of the eggs which have formed membranes develop into swimming
larvas that rise to the surface. These larvas develop into perfect
sea-urchin larvas or ' plutei ' as fast as the larvas of eggs fertilized
with sperm. It has lately been shown that pricking of the unfer-
tilized egg of a frog with a needle suffices to induce normal develop-
ment of the egg (Bataillon). These parthenogenetic frogs have been
successfully reared, and apparently are all males (Loeb). These
observations have an important bearing on the question of the deter-
mination of sex. In the frog it would seem that the eggs are all
alike, since in the absence of a spermatozoon only one sex (the male)
is developed. The male frog is hetero-gametic for sex — i.e., there
are two kinds of spermatozoa, one with and the other without a sex
chromosome. If a spermatozoon of the former type enters an egg,
a female is produced. If a spermatozoon of the latter type, or no
spermatozoon at all, enters an egg, a male is produced.
It is impossible to enter here into a discussion of the factors which
determine sex. While due weight must be given to such morphological
distinctions as sex chromosomes in the gametes (or sexual reproductive
elements), evidence has been adduced that the fundamental factor may
be chemical and metabolic pecularities in the gametes. In pigeons^ .g-.,
— in which the female is the hetero-gametic sex, producing two kinds
of eggs — it has been shown that the egg which is to develop a female
is characterized by a lower metabolism, a lower percentage of water
and a higher total content of fat and phosphorus or of phosphatides,
than the egg which is to develop a male. There are indications that by
changing these chemical conditions sex can be to some extent controlled
(Whitman, Riddle).
The facts of parthenogenesis show that it is not absolutely neces-
sary for development that the ovum should have the normal number
of chromosomes restored. It can develop with half the number, the
chromosomes of the female pronucleus being sufficient for growth,
although, of course, in this case for a growth uninfluenced by the
properties of the male element. In like manner it is stated that
portions of the maturated ovum devoid of a nucleus can undergo
development if penetrated by a spermatozoon, the chromosomes of
the male pronucleus being sufficient for growth.
Formation of the Embryo. — Not till all these events have taken place
— extrusion of the two polar bodies, or maturation ; penetration of the
spermatozoon, and blending of its head (the male pronucleus) with the
remnant of the nucleus of the ovum (female pronucleus), or fecundation
— not till then does the ovum begin the process of repeated division by
which the whole body is reproduced. The fused or segmentation nucleus
divides into two, each containing the normal number of chromosomes
derived from the splitting of those contributed by both the male and
female elements. It is believed that the division takes place in such a
way that both male and female chromosomes are represented in each
nucleus. The cytoplasm being also cleft by a corresponding furrow.
FORMATION OF THE EMBRYO 1125
two complete nucleated cells make their appearance. These divide in
turn, till at length (in the mammal) the embryo is represented by a
hollow sphere or vesicle, with a cellular crust. During division the
upper or outer cells have always been larger than the inner and lower,
and have multiplied more rapidly; and thus it comes about that the
hollow sphere of large cells encloses a mass of smaller cells, along with
remnants of broken-down yolk and of fluid derived by absorption from
the contents of the uterus. The smaller cells continue to multiply and
arrange themselves as a lining to the sphere already formed, so that in a
short time it becomes double, and we have already differentiated two of
the primary embryonic layers — the ectoderm, also called the epiblast, or
superficial, and the endoderm, also called the hypoblast, or deep layer.
The whole sphere is called the blastoderm, or the blastodermic vesicle.
While this inner shell of endodermic cells is gradually creeping on to
completion, there appears at a part where it is already fully formed a
small opaque whitish disc, the germinal area or embryonal shield. This
represents the stocks on which the framework of the embryo is to be laid
down. The area elongates; at its posterior end appears a thickened
line, the primitive streak, soon furrowed by a longitudinal groove, 'the
primitive groove, that marks the direction in which the long axis of the
future embryo will lie, but is not itself a permanent line in the building,
and ultimately vanishes. The appearance of the primitive streak is the
signal that a rapid proliferation of the cells of the germinal area, and
especially of the ectoderm, has begun ; and this goes on until a third layer
is formed, intermediate in position to the original two, and therefore
named the mesoderm. While this is pushing its way over the germinal
area and into the rest of the blastodermic vesicle, the ectoderm in front
of the primitive streak rises up in two lateral ridges, enclosing between
them the medullary groove. The medullary groove is the beginning of
the cerebro-spinal axis ; its walls first come to overhang the furrow, and
then to coalesce; and the medullary groove has now become the neural
canal. Immediately under it the mesoderm forms a rod of cells, the
notochord, which is the forerunner of the vertebral column ; around this
the bodies of the vertebrae are afterwards developed from cubical masses
of mesodermic cells, arranged in pairs along the notochord, and called
the protovertebra. The rest of the mesoderm, running out on each side
from the protovertebrae, splits into two layers, an upper or somatic layer,
which unites with the ectoderm, forming with it the somatopleure, and
a lower or splanchnic layer, which unites with the endoderm to form
the splanchnopleure. Between the somatopleure and the splanchno-
fleure is a space called the coelom, or pleuro-peritoneal cavity (Fig. 485).
he layer of ectoderm which envelops the whole (termed the tropho-
blast, from its nutritive function), in conjunction with the underlying
mesoderm, represents the prechorion, the early stage of the chorion.
Up to the present, apart from the enclosure of the neural canal, all this
formative activitv is buried beneath the surface of the blastoderm, and
has not showed itself by any external token ; the embryo still appears as
a portion of the germinal area, and lies in its plane. But now a pocket,
or crease, or moat, beginning at the head as the head-fold, then pushing
under the tail, gradually creeps round and undermines the whole
embryo, which is raised above the general level, and, as it were, scooped
out from the rest of the blastoderm; till at length it lies on the latter,
something like an upturned canoe, enclosing a tube, complete in front
and behind, but still open in the middle, where it communicates with
the interior of the yolk- vesicle. Since this tube has been formed by the
tucking in of the three ancestral layers of the blastoderm, it follows that
it is lined by endoderm, supported externally by the splanchnic sheet
1 1 26 REPRODUCTION
of mesoderm. So that now the body consists of a dorsal tube (the
neural canal), essentially of ectodermic origin, a ventral tube (the
alimentary canal), essentially of endodermic origin, and between the
two a massive double layer of mesodermic tissue, which contributes
supporting elements to both. At this point it may be well to emphasize
the fact that this embryological distinction of the three primitive layers
has a deep and fundamental meaning, and corresponds to a physiological
distinction that endures throughout life. The endoderm, the lowest
layer in position, may also be described as the lowest in the physiological
hierarchy. It furnishes the epithelial lining of the alimentary canal
from the beginning of the oesophagus to near the end of the rectum, as
well as the epithelium of the organs which arise from diverticula of the
primitive intestine — viz., the digestive glands (with the exception of the
salivary glands), the lungs, and the passages leading to them, the
thyroid, and the greater part of the thymus gland in its primitive con-
dition before tha lymphoid tissue derived from the mesoderm has as
yet grown into it. According to some authorities, the notochord is also
derived from the endoderm.
Upon the whole, it may be said that the tissues of endodermic
origin are essentially concerned in chemical labours, in the absorption
of food material and excretion of waste products. The mesodermic
tissues are essentially concerned in mechanical labour; they are the
tissues of movement and of passive support. The ectodermic tissues
are at the top of the pyramid; they govern the rest.
From the mesoderm arise the muscles, the entire vascular system,
with its blood- and lymph -corpuscles, the bones and connective tissues;
and the Wolffian body and its appendages, which are the predecessors
of the genital glands and ducts, and of the chief portion of the renal
apparatus.
The ectoderm forms the epidermis and its appendages, the epithelial
end-organs of the nerves of special sense, and the nervous system,
cerebro-spinal and sympathetic. The salivary glands and the mucous
lining of the mouth and anus are developed from the ectoderm, which
is indented to meet the intestinal canal and give it access to the exterior
at either end.
It is not possible here to trace in detail the development of all the
organs of the embryo. Its nutrition and metabolism not only dis-
tinctly belong to the physiological domain, but, carried on as they are
under conditions that seem so strange, and even so bizarre, to one
acquainted only with adult physiology, are calculated to throw light
on the metabolic processes of the fully-developed body. And they
cannot be understood without reference to the peculiarities of the
vascular system in foetal life. These we shall accordingly describe, but
for further details as to the anatomy of the embryo the student is
referred to some standard anatomical textbook, such as Quain's
' Anatomv.'
Pevelopment of the Connections between the Embryo and the
Uterus. — In the first period of its development the ovum, nestling in
the pouch formed by the decidua serotina and reflexa, Is fed from the
maternal blood and tissues directly, without the mediation of foetal
bloodvessels, through the finger-like processes or villi with which its
external layer, the zona pellucida, becomes studded. At the earliest
stage at which a human ovum has been studied after implantation it is
already enveloped by a thick ectodermic covering (the trophoblastic
envelope), consisting of two layers of cells, one unquestionably of fcetal
origin, the so-called cells of Langhans, and the other the syncytium, the
origin of which is assigned by some authorities to the ovum, by other*
FORMATION OF THE EMBRYO
1127
line of union
prechorion
amnon
somatop/eure
coelom
sptancfinopleure
to the maternal tissues. The trophoblastic covering is everywhere in
contact with the maternal blood, which, pushing its way into the tropho-
blast at intervals, divides it into columns. Later on the foetal mesoderm
grows into these, and so the primary chorionic villi are formed. It is
not till after the first three weeks that bloodvessels make their way into
these villi, although the mesoderm of the foetus begins to enter the villi
about the end of the first, or the beginning of the second, week. The
scanty yolk of the human
ovum is totally inade-
quate to supply it with
nutriment for the time
that elapses before the
bloodvessels are devel-
oped, and food sub-
stances must be obtained
from the maternal liquids
by imbibition, osmosis,
diffusion, • or filtration,
aided, perhaps, by more
special absorptive pro-
cesses on the part of the
foetal tissues. Soon the
heart appears as a tube
(at first double), formed"
by cells belonging to the
splanchnic layer of the
mesoderm. It begins to
pulsate in the chick as
early as the middle of the
second day, although it as
yet contains neither nerve-cells nor fully-formed muscular fibres. In
the mammal pulsation is late in making its appearance, in man about
the beginning of the third week. A bloodvessel grows out from the
anterior end of the heart and divides into two primitive aortic arches,
from each of which a vessel (omphalo-mesenteric cr vitelline artery] runs
out in the mesoderm covering the umbilical vesicle, or yolk-sac. The
blood is returned to the heart by the vitelline veins coursing in on the
walls of the vitelline duct. In this way the store of nutriment in the
umbilical vesicle of the chick, which is the only solid or liquid food it
receives or needs during the whole period of development, is tapped,
and a regular channel of supply established. Oxygen is at the same
time absorbed through the porous shell; but later on this respiratory
function is taken over by the second or allantoic circulation. In the
mammal the circulation on the umbilical vesicle is of much less conse-
quence, for the quantity of material left over after the formation of the
blastoderm is exceedingly small; it is only with a few days' provision
in its haversack that the embryo starts out on its developmental march.
And the vitelline vessels deriving their further supply of food and
oxygen from the tissues of the mother in contact with the ovum cease
to be of use as soon as the second and more perfect placental circulation
is established, and soon shrivel up and disappear, as the umbilical
vesicle shrinks.
The second circulation of the embryo is developed in connection with
a remarkable offshoot from the hind-gut called the allantois,_ which,
before the fifth day in the chick and during the second week in man,
pushes its way out between the somatic and splanchnic layers of the
mesoderm — i.e., in the pleuro-peritoneal cavity — and grows through the
Fig. 48-'. — Showing the Folds of the Somatopleure
in a Bird's Ovum uniting over the Embryo
and becoming demarcated into Amnion and
Prechorion (Keith).
1128
REPRODUCTION;
umbilicus, carrying bloodvessels along with it in its mesodermic layer.
Still earlier, and, indeed, while the embryo is being separated oft" from
and raised above
the level of the rest
of the blastoderm
by the deepening
of the ditch around
it, the further
banks of this fur-
row, formed of
ectoderm and
somatic mesoderm.
have risen up on
every side, and,
growing over the
back of the em-
bryo, have finally
coalesced and en-
closed it in a
double- walled
pouch (Fig. 485).
The superficial
layer of the pouch
Fig. 485 —Diagram to illustrate Formation of Amnion and js called the false
Allantois. A. cavity of true amnion; F, F', folds about amnion • it soon
to coalesce and complete the amniotic cavity; m, meso- Dlen(js 'with the
dermic layer of amnion; B, allantois; I, intestinal cavity tuftecj chorion or
of embryo; Y, yolk-sac; h, endodermic layer; e, ecto- ,
dermic layer of embryo. The embryo is the shaded por- ' >m.m
tion in the middle of the figure. E is placed over the envelope Ol
head region. No attempt is made to delineate its actual Ovum,
form. The mesoderm is represented by the interrupted layer persists as
line. the true amnion ; a
liquid, the amniotic
fluid, is secreted in the cavity which it encloses; and the embryo, loosely
anchored for the rest of its intra-uterine life by the umbilical cord alone,
floats freely within it. The amniotic fluid acts as a water-jacket or
cushion, to break the force of the inevitable shocks and jars transmitted
from the mother to the foetus and from the foetus to the mother. To
some extent, in addition, it may serve as a nutritive fluid, for substances
can pass from the blood of the mother into the amniotic fluid, and the
amniotic fluid can be swallowed by the foetus. This is shown by the
fact that sodium sulphindigotate, when injected into the maternal
circulation, is found in the amniotic fluid and in the alimentary canal
of the foetus, although not in any of the foetal tissues. Fine lanugo
hairs from the foetal skin have also been found in the meconium.
The precise origin and manner of formation of the amniotic fluid
have not been settled. It is probably in the main a maternal secretion
or transudation. But something is contributed by the foetus in the
form of renal, and perhaps of skin, secretions. The fluid is poor in
solids. Its maximum content of protein, reached during the first half
of pregnancy, is only 0-7 per cent. Later on it diminishes, and at full
term is only one-tenth of this amount. The specific gravity is 1006 to
1009. Its osmotic concentration, as measured by the depression of the
freezing-point, is less than that of the mother's blood-serum.
The allantois, growing out at the umbilicus, in the manner described,
insinuates itself between the true and false amnion, and soon blends
with the latter. For a time the secretion of the primitive kidneys
continues to be poured into the cavity of the allantois, so that it serves
NUTRITION OF THE EMBRYO 1129
in pa*-t as an excretory organ, while in the bird it also performs the
function of respiration ; and in the mammal both food ana oxygen are
carried by its vessels to the foetus during the greater part of intra-
uterine life. But later on the outgrowth atrophies and disappears, all
except its origin from the alimentary canal, which dilates and persists
as the urinary bladder, and its bloodvessels, which grow in the form of
tufts or loops into the chorionic villi. The vessels are fed by two
umbilical arteries which arise from the hypogastric arteries and run out
at the umbilicus on the allantois. The blood is returned by an umbilical
vein, whose further course we shall have soon to trace. The shrivelled
stalk of the allantois, projecting through the umbilicus, takes part, with
its bloodvessels, in the formation of the umbilical cord, which contains
also the remains of the yolk-sac and is clothed externally by a layer of
the amnion. Continuous with the umbilical cord, and stretching from
the umbilicus to the urinary bladder, is a portion of the allantois which
is represented in extra-uterine life by a thin cord-like structure, the
urachus. The vascular tufts of the chorion, which at first cover the
whole surface of the ovum and suck up food and oxygen from decidua
serotina and reflexa alike, disappear in the region of the reflexa, hyper-
trophy all over the serotina — that is, where the ovum is in actual contact
with the uterine wall — and this part of the chorion is now distinguished
as the chorion frondosum. The giant villi of the chorion frondosum
push their way into the thickened decidua serotina, and ultimately
penetrate into the great capillaries or sinuses of the uterine mucous
membrane. At the same time the tissue of the villi external to the
vessels becomes reduced to a mere film, so that, except for a thin cover-
ing of decidual cells, the foetal vessels are bathed in maternal blood.
By this interweaving of decidua and chorion frondosum is formed the
placenta, which for the rest of intra-uterine life acts as the great
respiratory, alimentary, and excretory organ of the foetus.
Exchange of Materials in the Placenta. — The maternal blood, as
it streams through the colossal capillaries of the decidua, gives up
to the foetal blood oxygen and food substances and receives from it
carbon dioxide and in all probability urea. It is true that the blood
in the uterine sinuses is not itself fully oxygenated; it is not bright
red arterial blood. But it yet contains more oxygen, and oxygen at
a higher partial pressure (p. 247 ), than the purest blood of the foetus,
and is, therefore, able to part with some of the surplus to the dark
stream of oxygen-impoverished blood brought by the umbilical
arteries to the placenta. Thus, it has been found that while the
blood of the umbilical artery of the foetus of a sheep had 47 volumes
per cent, of carbon dioxide, and only 2-3 of oxygen, that of the
umbilical veins had 6-3 volumes of oxygen, and only 40-5 of carbon
dioxide (Zuntz and Cohnstein). In the exchange of gases between
the placental and the foetal blood the same general features present
themselves as in the external and internal respiration of the mother,
with this difference, that the exchange of oxygen is neither between
air and haemoglobin, as in the lungs, nor between haemoglobin and
tissue elements, as in the organs; but between maternal and foetal
haemoglobin, of course, through the mediation of the maternal and
foetal plasma. There is no reason to suppose that the mechanism
1 1 30 REPRODUCTION
of the exchange is essentially different from that of the more familial
forms of respiration. Diffusion of the gases from places of higher
to places of lower tension unquestionably plays an important
part. But this does not exclude the possibility of a more active
process of some other kind, although there is at present no direct
evidence of such a gaseous secretion as has been previously discussed
in connection with pulmonary respiration (p. 262). The presence of
oxydases in the placenta does not throw any light on the question.
For there is no proof that they act in transferring oxygen from the
one circulation to the other, and oxydases are found in the most
diverse tissues. Their significance for the combustion processes of
the body has already been alluded to (p. 271 ).
Salts soluble in water, including not only those necessary for
nutrition, like sodium chloride, but many foreign salts, pass readily
from the placenta to the foetus, and in general more easily the lower
their molecular weight. Such salts as potassium iodide, e.g., when
injected into the maternal circulation, appear in the foetus in a very
short time. On the other hand, colloidal solutions — e.g., of silver
or silicic acid — do not pass over at all. It is of practical importance
that substances like chloroform, ether, and other narcotics, and alka-
loids like morphine and scopolamine, when administered in obstetrical
practice, may find their way from the mother to the child, although
more slowly and more capriciously than the salts. While diffusion
and osmosis assuredly take part in the passage of materials from the
placenta to the foetus, there is no more reason to conclude that the
whole exchange, even for the salts, depends upon such simple physical
processes than there is in the case of the exchange between any one
of the maternal tissues and the maternal blood. The essential
similarity of placental and intestinal absorption, to take one instance,
is seen in the mechanism by which the foetus gains the iron required
for the development of its haemoglobin. The haemoglobin of the
mother appears to be the most important source of this iron.
Erythrocytes in all stages of decomposition can be found in con-
tact with the chorionic villi, and even in the epithelium covering
the villi. These corpuscles come partly from extravasations in
the maternal portion of the placenta, but it is possible that the
villi also possess the power of haemolyzing intact corpuscles in the
circulating placental blood. Iron can be demonstrated by micro-
chemical reactions in the epithelial cells of the chorionic villi as fine
granules, which increase in size towards the base of the cells. As we
pass deeper into the villus towards its central bloodvessel, the
granules again diminish in size. The picture is very like that seen
in the absorption of iron from the intestine. And if the micro-
chemical picture is practically the same, the process by which the
iron is absorbed is not likely to be fundamentally different m the
two cases (p. 447).
NUTRITION OF THE EMBRYO 1131
The same is true of the passage of fat across the placenta. Fat
can always be demonstrated microchemically in the chorionic villi.
The most superficial layer of the villi is free from visible fat droplets.
They increase in number towards the base of the epithelial cells.
As in the case of the intestine, these appearances agree well with
the view that the fat is split before being absorbed by the villi, and
undergoes resynthesis in the epithelium. That, as a matter of fact,
fat passes from the mother to the foetus is shown by the observation
that when pregnant guinea-pigs were fed with a foreign fat (from
cocoanuts), the characteristic fatty acid (lauric acid) was found in
the foetus. This, however, does not exclude the possibility that the
foetus may form fat in its own tissues from carbo-hydrates, and
perhaps from proteins, as it is destined to do in extra-uterine life.
Among the carbo-hydrates the passage of dextrose from the
maternal to the foetal blood has been experimentally demonstrated
A specially interesting proof is afforded in cases where the mother
suffers from diabetes mellitus. In one case in which the mother,
during diabetic coma, was delivered of a stillborn child, the blood
of the child contained 2-2 per cent, of sugar, its urine 5-24 per cent.,
and the amniotic fluid 0-47 per cent. The blood of the mother had
a sugar content of 0-8 per cent., and her urine a content of 6-94 per
cent. The sugar of the maternal blood is not the only source of the
carbo-hydrates of the foetus. The glycogen store of the placenta is
to be regarded as a second source, which is rendered available on
conversion into dextrose by the placental diastatic ferment. This
store of easily available food material is especially important in the
early stages of development of the ovum before a circulation has
been established in the villi. In the youngest ova investigated the
decidual covering has been found rich in glycogen.
While it is to be supposed that the products of the hydrolytic
decomposition of proteins can be absorbed by the foetal blood in its
passage through the placenta, to be synthesized to the appropriate
tissue proteins in the foetal organs, there is evidence that certain
proteins can be taken up without change. In this connection it
must be remembered that the mother is much more closely related
to the foetus as regards her protein composition than any ordinary
protein food can be to an animal in extra-uterine life. In some
respects, indeed, the foetus may be considered, especially, perhaps,
in the first stages of its development, as a part of the mother, an
additional, although very complex, organ rather than an independent
organism.
The blood of the umbilical artery, although far from the level of
the ordinary arterial blood of the mother as regards its gaseous
content, is yet the best the foetus ever gets; and by a series of con-
trivances it is assured that this best should go first to the most
important parts — the liver, the heart, and the head — while the legs
1 1 32 REPRODUCTION
and most of the abdominal organs have to put up with an inferior
supply. This is brought about mainly by the existence of three
short-cuts for the blood, which disappear in the adult circulation, the
ductus venosus, the ductus arteriosus, and the foramen ovale.
The blood of the umbilical vein, rich in oxygen for foetal blood,
passes partly through the circulation of the liver, but a part takes
the route of the ductus venosus, and empties itself into the inferior
vena cava. The latter gathers up the more or less vitiated blood
from the inferior extremities and the renal and hepatic veins, and
pours its mixed, but still fairly oxygenated,, contents into the right
auricle. By means of the Eustachian valve, the jet coming from
the mouth of the inferior vena cava is directed into the left auricle
through the foramen ovale in the inter-auricular septum. There
it is joined by the trickle of blood which is creeping through the
unexpanded lungs. The left ventricle propels its contents through
the aorta, and thus a large part of this comparatively pure or
second-best blood is sent to the head and upper extremities. It
returns in a vitiated state by the superior vena cava into the right
auricle, and owing to the position of the Eustachian valve and the
direction of the current, it flows now, not through the foramen ovale,
but into the right ventricle. Thence it is driven through the pul-
monary artery, but only a small quantity of it finds its way through
the lungs; the main stream is short-circuited through the ductu?
arteriosus, and mingles with the contents of the thoracic aorta
below the origin of the cephalic and brachial vessels.
We may now give something more of precision to the statements
that different parts of the body receive blood of different quality;
and it is possible roughly to divide the organs in this respect into
four categories : (i) The liver, which partakes both of the best and
the worst, the purified blood of the umbilical veins and the vitiated
blood of the intestines and spleen; (2) the heart, head, and upper
limbs, which receive the blood from the inferior extremities and
kidneys, mixed with the pure blood of the venous duct; (3) the
legs, trunk, intestines, and kidneys, which are fed chiefly by the
off-scourings of the cephalic end, mitigated, however, by a pro-
portion of mixed blood from the inferior cava; (4) the lungs, which
receive only a feeble stream of unmixed venous blood.
These peculiarities of the embryonic circulation are in obvious
correspondence with the physiological events taking place in the
foetal body. The liver is not only the greatest gland in the embryo,
as it continues to be in the adult, but its activity seems to dwari
that of all the other glands put together, and is in striking contrast
with the functional torpor of the lungs. From the third month of
intra-uterine life the secretion of bile begins and the intestines
gradually fill with meconium, of which the principal constituent is
bile. Accordingly the liver is most lavishly supplied with blood,
NUTRITION OF THE EMBRYO 1133
while the lungs are stinted. And since the liver has, as we have
already learnt, other and, in the adult at least, even more important
labours than excretion, a large portion of the blood it receives
is of the best quality: it enters the gland comparatively rich in
oxygen, and passes out comparatively poor; while the lungs, which
have to be nourished only for their own sake, and are of no use
whatever till the child is born and respiration has begun, must be
content with the poorest fare — with the crumbs that fall from the
table of fcetal nutrition. The full-fed cephalic end of the embryo
grows far more rapidly than the half-starved inferior extremities,
and the head of the new-born child is large in proportion to the rest
of the body.
Metabolism of the Embryo. — There are some other points in the
physiology of intra-uterine life which call for remark; and, to sum
up in a few words the grand distinction between foetal and adult
life, we may say that growth is the keynote of the former, work
(functional activity) of the latter. Thus, the muscles at an early
period in their development, long before any glycogen can be
found in the liver, become the seat of an accumulation of glycogen,
which, since it cannot be used up in contraction as in the adult
muscles, seems to be intimately connected with their own growth,
and perhaps also with the growth of other tissues. It is true
that the fostal tissues as a whole, including the muscles, are not
richer, as used to be taught, but poorer in glycogen than adult
tissues, and therefore the old doctrine that the foetal glycogen fulfils
a special ' formative ' function in the development of the tissues,
has lost its experimental basis. Nevertheless, there is a paral-
lelism between the growth of the foetus and its glycogen content.
In cases where the growth of the foetus has been spontaneously
arrested, the percentage amount of glycogen in its organs has been
found to be diminished out of proportion to the diminution in weight.
A similar retardation of development can be produced by repeatedly
injecting phloridzin into the mother, and thus reducing the glycogen
store of the foetus (Lochead and Cramer). Probably, then, the foetal
glycogen assists the growth of the embryo, which is known to be
accompanied by an intense carbo-hydrate metabolism, by furnishing
a store of easily oxidized material for the nutrition of the developing
tissues. When the muscles have been formed, their glycogen is
still consumed in growth, and their functional powers lie dormant,
but for the infrequent and feeble movements, generally regarded as
reflex, but possibly to some extent originated in the cerebral cortex,
which give the mother the sensation of ' quickening.' It is only
late in development that the embryonic liver takes on its glycogenic
function. In the earlier stages it is entirely free from glycogen. It
is an interesting illustration of that exact adaptation of means to
ends which so constantly impresses the investigator of the animal
1 1 34 REPRODUCTION
mechanism that the ferment which converts glycogen into dextrose
(glycogenase) is a?so either entirely absent from the liver earl}' in
gestation, or present only in traces ; and that as the glycogen-forming
and glycogen-storing functions of the organ increase in importance, it
becomes richer in glycogenolytic ferment. It cannot be doubted that
the glycogen found in the placenta is also deposited there in the
interest of the rapidly growing foetal tissues, perhaps as a kind of
current account on which they can operate at any moment of
emergency, when the more distant maternal reserves cannot be
drawn upon in time. The glycogen is formed in the placenta, prob-
ably from the dextrose of the maternal blood. By means of a
glycogen-splitting ferment, which can be extracted by glycerin from
the placenta, the glycogen appears to be reconverted into dextrose
for absorption by the foetus. In the earlier period of gestation the
placenta seems to perform vicariously the glycogenic function of the
liver, and as the glycogen content of the liver increases in the later
stages of intra-uterine life, that of the placenta diminishes pro-
portionally.
The excretory glands of the embryo, except the liver, scarcely
awaken to activity during foetal life. Urine may indeed be some-
times found in the bladder at birth, but it is often absent. It is a
dilute urine, with a molecular concentration only about half as great
as that of the blood, and although a portion of the amniotic fluid,
which contains traces of urea and salts, in addition to smaU quantities
of albumin, may be secreted by the renal tubules, and find its way
through the still open urachus into the amniotic sac, this contribution
cannot imply more than a slight degree of glandular action. Under
certain experimental conditions, however, it can be largely increased.
Thus, extirpation of the kidneys in a pregnant animal causes an
increase in the amount of amniotic fluid (hydramnios) through the
stimulation of the foetal kidneys to increased activity by the passage
of the unexcreted urinary constituents of the mother's blood into
that of the foetus. After the injection of phloridzin into the foetus
sugar has been found in abundance in the amniotic fluid, although
the injection of that drug into the mother caused no such effect. On
the other hand, after injection of sodium sulphindigotate into the
circulation of the foetus in the sheep, the foetal kidneys contained
particles of the pigment, while the amniotic fluid remained un-
coloured. Long before full term the sebaceous glands have
begun their work by the secretion of the vernix caseosa, an
oily material which covers the skin and serves to protect it
from the continual irritation of the fluid in which the embryo
floats.
The nervous system is even less active than the glandular tissues,
and not more active than the muscles. There is evidently no scope
for the exercise of the special senses. Psychical activity of every
NUTRITION OF THE EMBRYO 1135
kind must be at its lowest ebb. Consciousness, if it exists at all,
must be dull and muffled. And if motor impulses are discharged
from the cortex, the psychical accompaniments of such discharge are
doubtless widely different from those which we associate with
voluntary effort.
It is a remarkable fact that this functional calm, broken only by
the beat of the heart, is accompanied by a relatively intense
metabolism of the same order of magnitude as that of the adult.
In the hen's egg at all stages of development the consumption of
oxygen and production of heat (per kilogramme and hour) are the
same as in the adult hen. The oxygen consumption and carbon
dioxide production of pregnant guinea-pigs were determined before
and during compression of the umbilical cord of a foetus, and a dis-
tinct diminution was observed when the respiratory exchange of the
foetus was eliminated. From the results of a number of observations
it was calculated that the carbon dioxide produced by the mother
was 462 c.c., and by the foetus 509 c.c. per kilogramme of body-
weight per hour (Bohr and Hasselbach). A similar comparison
between women before and during pregnancy never showed any
diminution in the respiratory exchange reckoned on the unit of body-
weight in the pregnant condition. In one case, indeed, and that
the most exactly observed, there was an increase in pregnancy.
Now, in the pregnant woman a considerable part of the increase of
body-weight is due to the amniotic fluid, in which, of course, meta-
bolism does not go on. It is evident, then, that in the human fcetus
also the intensity of metabolism is at any rate not of a lesser order of
magnitude than in the mother, in spite of the much smaller amount
of muscular contraction taking place. The heat production of mother
and child together has been directly estimated in several cases in a
respiration calorimeter provided with a bed just before parturition
and just after it. After parturition the heat production of the
mother was also separately determined. From the difference it was
concluded that the heat production of the child per kilogramme
of body-weight per hour is approximately two and a half times
that of the mother under the same conditions. (Carpenter and
Murlin.)
The foetal heart beats at the rate of about 140 times a minute at
full term.* The blood-pressure in the umbilical artery of the
mature embryo (sheep) varies from 60 to 80 nun. of mercury;
but at the beginning of the aorta it will be more. The pressure in
* It has not been finally determined whether the rate of the heart varies
with the size or, what probably comes to the same thing, with the sex of the
foetus. As we have seen, the variation of the rate in the adult with the size
of the body is associated with a corresponding variation in the metabolism
and heat-loss, which are proportionally greater in a small than in a large
animal. If this is a causal connection we should not expect that in the
embryo in utero, where the conditions as regards heat-loss are entirely different,
such a relation should exist, at any rate within the same species.
ti36' REPRODUCTION
the pulmonary trunk must be about equal to that in the aorta, since
the comparatively short and easy circuit through the lungs does
not as yet exist ; and in accordance with this equality of pressure
(of work to be done) is the equality of thickness (of working power)
in the walls of the two sides of the heart.
Suppose, now, that the embryo contains 60 grammes of blood for
every kilo of body-weight, and that the whole of the blood passes
through the circulation in twenty seconds. Then in twenty-four
hours 259-2 kilos of blood will be forced through the heart for every
kilo of body-weight against a pressure of, say, 80 mm. of mercury,
or i metre of blood. This is equivalent, in round numbers, to 260
kilogramme-metres of work, or 0-6 calories. Now, taking the total
heat-production of the heart at three times the equivalent of its
mechanical work, we get 1-8 calories per kilo of body- weight in
twenty-four hours (see p. 676), or about ^ of the heat-production
of a resting adult.
Such movements of the skeletal muscles as occur cannot account
for any large proportion of the total metabolism, since they are
executed in a medium (the amniotic fluid) of nearly the same specific
gravity as that of the body, and therefore require the expenditure of
a very limited amount of energy. The ordinary functional activity
of the embryo, then, is quite incapable of accounting for the intensity
of the foetal metabolic processes. Still less can it be due to an active
combustion in the tissues to compensate for a rapid loss of heat,
for the foetus lies sheltered in the uterus as in a thermostat at its
own temperature, and can lose practically no heat unless its tempera-
ture be kept a little above that of the maternal blood. The only
remaining explanation of the magnitude of the foetal metabolism
is that the growth processes are associated with a large amount of
oxidation (and cleavage).
Notwithstanding the intensity of metabolism in the embryo, not
only is even the purest blood, as has already been stated, far from
saturated with oxygen, but the relative proportion of haemoglobin,
the oxygen-carrier, is less than in the adult ; and although constantly
increasing in amount from the moment of its first appearance, it is
still somewhat deficient, even at full term, but leaps sharply up at
birth. At an early period of development the embryo also contains
much more water than the adult; the specific gravity of its tissues
increases as development goes on.
The remarkable vitality of the foetus, and its resistance to
asphyxia, are related not to the feebleness of its metabolism, but to
the comparatively slight excitability and high endurance of nervous
centres like the respiratory, vaso-motor, and cardio-inhibitory.
Even when totally deprived of oxygen, as by pressure on the um-
bilical cord during delivery, the child does not perish in the two or
PARTURITION 1137
three minutes which decide the fate of the asphyxiated adult ; nor are
the convulsions, rise of blood-pressure, and slowing of the heart-beat
associated with asphyxia in the latter, so readily induced, nor
premature and fatal efforts at respiration easily excited in utero.
But although in such a case the embryo behaves as a separate
organism, governed by its own laws, there are circumstances in
which it becomes merely a part of the mother and participates in her
fate. Thus, the stream of oxygen which normally passes from the
maternal to the foetal blood is turned back if asphyxia threatens
the mother; the blood of the umbilical arteries, instead of being
purified in the placenta, loses the little oxygen it holds to the
blood of the uterine sinuses, and the tissues of the embryo are
impoverished to support the metabolism of the maternal organs.
In the same way, the phenomena of starvation have taught us
that the nutrition of the organism is not subject to the rules of
red tape. In normal circumstances the flow of nutriment follows
definite lines: the blood feeds the tissues through its intermediary,
the lymph, and recoups itself from the contents of the alimentary
canal. But when the normal sources of nutrient material fail, the
body falls back upon its stores. The organs immediately necessary
to life are kept, as far as possible, on full diet ; organs of secondary
importance have to be content with half-rations; organs less im-
portant still are drawn upon for supplies.
Parturition. — The period of gestation is abruptly closed about
280 days after the last menstruation, usually in what would have
been the tenth intermehstrual period had menstruation been occur-
ring. There is necessai'ily a considerable variation in the time when
reckoned in this way, since the cessation of the menses merely an-
nounces that conception has occurred some time after the last
period. It may even be disputed whether the fertilized ovum
corresponds to the last menstruation or to the first absent
period. Parturition, or the expulsion of the foetus, is accom-
plished by periodical contractions, the ' pains ' of labour, at first
confined to the uterus. Soon the os uteri begins to soften and
dilate, the walls of the vagina become congested, and its secretions
are augmented. The uterine contractions increase in frequency
and force, and are now accompanied by reflex contractions of the
abdominal muscles, and, if the woman is not anaesthetized, also by-
voluntary contractions of these and of other muscles, which can
increase the intra-abdominal pressure. The uterine contractions
can be initiated and modified by impulses coming from the central
nervous system by way of the extrinsic nerves of the organ. It is
known, e.g., that the gravid uterus can be excited to contraction by
the stimulation of various sensory nerves. Powerful mental impres-
sions, such as fright, may bring on premature labour. Conversely,
sudden cessation of labour pains during parturition is not uncom-
72
H38 REPRODUCTION
monly observed to be produced by emotional disturbances — for
instance, the entrance of a stranger into the room. Yet the con-
tractions of the uterus are not essentially dependent upon extrinsic
impulses. For not only do rhythmical contractions occur, but the
whole process of parturition has been seen to take place in a uterus
whose nerves have all been cut. Even the excised uterus may be
kept alive for as long as forty-eight hours, and may go on executing
periodical contractions when its bloodvessels are perfused with such
an artificial fluid as Locke's solution, or, indeed, when it is simply
immersed in the oxygenated solution (Kurdinowski) (Practical
Exercises, p. 1147).
It is a question of great interest how the uterine contractions are
started so abruptly at full term after so long a period of quiescence.
It can hardly be that the increasing mechanical distension of the
uterus, tolerated for so many months, should suddenly, in an hour,
become intolerable. For if the foetus dies before full term it is
expelled without reference to the bulk which the uterus has reached.
It is more likely that some chemical change associated with the
completion of intra- uterine development, a change which leads,
perhaps, to the production of some specific substance in the placenta
or the foetus, is the determining event. The placenta is a structure
whose function is strictly limited to the term of intra-uterine develop-
ment. The foetus is to live on, and so is the mother. May it not
be that the placenta or essential elements in it are timed to die, or
to begin to die, at full term, and that in their death or degeneration
the substance or substances are produced which start, and later
sustain, the uterine contractions ? And may not the contractions of
the uterus, by exciting its afferent nerves, or through the pressure
of the foetus the afferent nerves of the vagina, in turn evoke the
associated reflex contractions of the abdominal walls ? These are
questions which have been asked, but not as yet satisfactorily
answered. It has also been suggested that a hormone formed in the
mammary gland at full term stimulates the uterus and thus brings
on labour.
At birth, great changes take place in the foetal circulation, and these
are intimately connected with the commencement of the respiratory
activity of the lungs. The causes of the first respiration are: (i) The
increasing venosity of the blood circulating in the bulb, which stimu-
lates the respiratory centre when the umbilical cord has been cut o:
tied and the placental circulation thus interfered with ; (2) the stimula-
tion of the skin by the air, which, as we have seen, acts reflexly upon the
respiratory centre. That both of these factors may be involved is
shown by the fact that either compression of the umbilical cord alone,
or exposure of the foetus by opening the uterus of an animal without
interference with the circulation, has been observed to be followed
by attempts at breathing. Once distended, the lungs never again
completely collapse — not even after death, nor when the chest is
opened. The aspiration caused by the elevation of the chest- walls in
MILK 1139
inspiration (for the respiration of the newborn child is mainly costal)
SUCKS blood into the thorax, and expands the vessels of the lungs for
its reception ; and in the measure in which the blood passing through the
pulmonary trunk finds an easy way through the lungs, the quantity
which takes the route of the ductus arteriosus diminishes. The pul-
monary veins, and consequently the left auricle, are better filled ; and
the increasing pressure on this side of the septum tends to oppose the
passage of the blood through the foramen ovale, to approximate its
valve, and to close its orifice.
By the second or third day the ductus arteriosus has usually become
obliterated. The umbilical arteries and veins and the ductus venosus
become impervious soon after the interruption of the placental circula-
tion. The vein and venous duct remain in the adult as the round
ligament of the liver, the arteries as the lateral ligaments of the bladder.
Although from birth onwards the young mammal obtains its
oxygen and gets rid of its carbon dioxide through its own pulmonary
surface instead of through the placenta, it still lives, as regards its
food proper, on the tissues of the mother, and that in as literal a
sense as when it drew its supplies directly from the maternal blood.
Milk. — The milk secreted during the first few days of each lacta-
tion, the colostrum, as it is called, indeed may represent in part the
fragments of cells lining the alveoli of the mammary glands, which
have undergone a fatty change and been bodily broken down. The
colostrum corpuscles are leucocytes filled with fat globules taken up
from the contents of the alveoli. The chief chemical difference
between colostrum and ordinary milk is the greater richness of the
former in protein. It has been supposed that it is of special impor-
tance for the nutrition of the suckling, perhaps in virtue of the
enzymes contained in it, and it is said that young animals bear
artificial feeding much better if they have been allowed to suckle the
mother for the colostrum.
In addition to the fat, which when milk is allowed to stand rises to
the top as cream, milk contains a considerable quantity of caseinogen,
to whose coagulation, under the influence of the lactic acid produced
from the lactose, or milk-sugar, by certain bacteria, spontaneous
curdling is due. Another protein, lact-albumin (Halliburton), a large
amount of water, and some inorganic salts, are the most important of its
remaining constituents. Recently the presence of small amounts of
phosphatides intimately associated with the protein constituents, and
possibly combined with them as ' lecith-albumins ' has been shown
(Osborne and Wakeman) . The molecular concentration (p. 426) of milk,
as measured by its freezing-point, is almost exactly the same as that of
blood-serum. Its electrical conductivity varies extremely, since it
depends on the quantity of fat present, the fat globules, like the blood-
corpuscles, being practically non-conductors. The hydrogen-ion con-
centration of fresh cow's milk has been found to vary from 0-18 . io~8N
(PH— 6-75*) to 0-25 . io-6N(PH=6-6o) in the great majority of specimens.
* Instead of expressing the hydrogen-ion concentration as a fraction of ar
normal solution, it is more convenient for many purposes to take as a measure
of the concentration the logarithm of this number, omitting the negative sign,
represented by the symbol P. .
REPRODUCTION
This is distinctly greater than the hydrogen-ion concentration of blood.
— 6-io -8(PH =7-2) to 2-io-8(PH = 7'7). During the course of rennin
action there is no change in the hydrogen-ion contentration of milk
(Milroy ) .
The inorganic composition of milk is particularly interesting when
compared with that of the blood on the one hand and that of the
suckling on the other. Thus, 100 grammes of ash from each source
gave the following values for the rabbit (Abderhalderi) :
Rabbits (14 Days
Old.
Rabbit's Milk. Rabbit's Blood.
Rabbit's Blood-
Serum.
K2O
10-84
10-06
23-75
3-19
Na2O
5'96
7-92
3I-38
54-72
CaO
35'°2
35-65
0-81
1-42
MgO
2-19
2-20
0-64
0-56
Fe203 . .
0-23
0-08
6-93
o-oo
P205
41-94
39-86
ii-ii
2-98
Cl
4'94
5'42
32-66
47-83
The richness of the milk (and of the suckling) in calcium, phos-
phorus, and magnesium, as compared with the serum, is to be especially
remarked. This is, of course, essential for the development of the
bones. Whereas sodium predominates greatly over potassium in the
serum, the opposite is the case in the milk (and the suckling). This is
connected with the development of the tissue cells, which are richer in
potassium than in sodium. The high chlorine content of the serum is
in sharp contrast with the relative poverty of the milk in that element,
which preponderates in the tissue liquids and is relatively scanty in the
cells.
In addition to substances susceptible of chemical analysis, milk
contains enzymes like those present in blood-serum, including
oxydases and various hydrolytic ferments (proteolytic, diastatic,
and perhaps lipolytic). It is now universally acknowledged that
mother's milk is superior for the feeding of the infant to any
artificial substitute and one factor in this superiority may be the
presence of ferments specifically adapted for the digestion of the
human suckling. More important is the practical sterility of the
human milk and the necessarily finer adaptation of its quantitative
and qualitative composition, particularly the closer relationship of
its proteins with those of the child. In addition, there is some
evidence that the maternal milk contains immune bodies (anti-
bodies) which may increase the resistance of the suckling to
infections.
However this may be, there is no question that much of the high
infant mortality associated with the industrial conditions of our
great cities could be prevented if breast-feeding were carried out by
every mother physically capable of it.
As to the manner in which milk is secreted, there is no doubt
that its chief constituents are formed in the gland-cells. Caseinogen
CULTIVATION OF TISSUES 1141
and lactose do not exist in the blood or lymph. The former is
probably produced by an alteration in one or other of the serum
proteins, the latter by a change in the dextrose of the blood. The
fat of the milk may come partly from the fat of the blood, but it
may also be formed in the gland-celte from proteins, and carbo-
hydrates. The precise manner in which the fat globules are extruded
from the cells into the lumen of the alveoli is not clear, but there is
no good ground for believing that the cells or their free ends break
up bodily in the process.
Little is known as to the influence of the nervous system on the
secretion of milk, and no definite secretory fibres have as yet been
clearly demonstrated, although the fact that marked changes may
be produced in the milk of nursing women as the result of emotional
disturbances indicates that such nerves do exist. There is reason
to suppose that the stimulus for growth and development of the
mammary glands may be distinct from the stimulus which causes
increased secretion. Some observers lean to the opinion that milk
secretion is governed in an important degree by hormones carried
to the glands in the blood. The effect of- pituitrin has already been
alluded to (p. 669.).
Pregnancy is accompanied with vascular dilatation and hyper-
trophy of the mammary glands, but the mechanism by which these
changes are produced is unknown. It is probable that they depend
upon some internal secretion of the ovary or some other of the
organs of reproduction. Pregnancy is not an absolutely indispens-
able condition, and therefore it would seem that the exciting
substance, if any specific substance exists, is not a product of the
foetus or of the placenta. Intravenous injection of extract of
placenta is said to cause an increase in the flow of milk in goats, and
the deduction has been drawn that some ' internal secretion ' of
the placenta may be responsible for initiating the activity of the
mammary gland at the time of parturition. But precisely similar
phenomena are occasionally seen in animals which have not been
impregnated and even in men. Humboldt relates the case of an
Indian father, who so well understood the responsibilities of pater-
nity, and was so capable of fulfilling them, that he suckled his child
for five months on the death of the mother. Virgin bitches are
frequently known to produce milk, occasionally even in quantity
sufficient to rear pups, the flow occurring about the time when they
would have whelped had they conceived during the previous oestrus.
Bitches which after copulation have ' missed ' having pups have
been known to produce so much milk, beginning at the time they
were due to whelp, that they were able to rear litters of puppies
belonging to other bitches. Mules, which are themselves sterile,
may have enough milk to suckle a foal. The nipples of certain
monkeys become swollen and congested at each menstruation
1 142 REPRODUCTION
(Heape), and in women some development of the mammary glands
is often associated with the menstrual period. The stimulus to the
development of the gland in these cases appears to be some change
correlated with oestrus, and cannot be a change correlated with
pregnancy.
Cultivation of Tissues outside of the Body.- — Closely related to the
marvellous power of growth of the fertilized ovum in the favourable
nidus of the pregnant uterus, although, of course, incomparably
inferior, is the power of growth and reproduction of isolated tissue
cells in a suitable medium outside of the body. An instance of this
has already been described in the case of nerve-cells (pp. 803, 857).
Many other tissues have been successfully cultivated in sterile
coagulated lymph or blood-plasma. Connective-tissue cells grow
very easily, and can apparently be preserved indefinitely in the
living state. A strain of these cells, originally obtained from a
fragment of the heart of an embryo chick which had been pulsating
in vitro for 104 days, has been seen to proliferate rapidly outside of
the organism for more than sixteen months, and after more than
190 passages into fresh media. At the end of this time the rate of
proliferation of the connective-tissue cells was even greater than
that of fresh connective tissue taken from an embryo eight days old.
Extracts of tissues and tissue juices under certain conditions acceler-
ate the growth of connective tissue from three to forty times, the
growth being measured by the increase in area of the minute pieces
of tissue. This activating power is especially marked in extracts
of embryos, of adult spleen, and of certain sarcomas. This is
noteworthy as the great characteristic of malignant tumours is
their indefinite power of growth. The activating substance is
unable to pass through a Chamberland filter (Carrel). Cultures of
adult tissue have a smaller power of persistent growth. In the
majority of cases growth in plasma without the addition of a
stimulating tissue extract ceases after three or four generations
(Walton).
The time of survival of tissues at low temperatures under con-
ditions which do not encourage growth is also a matter of consider-
able interest, both from the physiological and the practical point of
view, since living sterile tissue is required for a number of surgical
operations — for example, skin for grafting. Skin has been suc-
cessfully grafted after being kept two to seven weeks in cold storage,
but after a longer period there were many failures. Embryonic
chick and rat tissues live longest at about 6° C., but not more than
twenty days under the most favourable conditions, according to
Lambert.
Transplantation of Tissues. — Besides the growth and regeneration
of tissues or organs, the simple displacement of them from their
normal situation and their implantation in a new environment have
TRANSPLANTATION OF TISSUES 1143
been studied. Normally, a migration of tissue elements is only
witnessed in the adult in the case of cells moving with the circulating
liquids, or endowed with the power of amoeboid movement. Under
pathological conditions fragments of tissue, such as tumour cells,
may be carried by the blood or lymph to distant parts, and, settling
there, may undergo development (forming metastases). In the
embryo the slow migration of tissue elements is a process which
is responsible for some of the anatomical pecularities of the adult.
The migration of the ovum from the ovary is the starting-point of
the process of reproduction. The artificial displacement of tissues
within the body of one and the same animal (auto-transplantation
or autografting) can be successfully accomplished in the case of
most normal organs and tissues, and also in the case of most tumours.
Instances have already been given in speaking of the endocrine
functions of the ovary, thyroid, spleen, thymus, etc. (Chap. XL).
A small piece of tissue or sometimes a small organ is simply inserted
in its new situation without provision for the immediate establish-
ment of a circulation. Necrosis of the central portion occurs, but
the peripheral zone soon becomes vascular, the graft ' takes ' and
under suitable physiological conditions grows. Hetero-transplan-
tation, or grafting between animals of different species, does not
succeed. Homceo-transplantation, or grafting from one animal to
another of the same species, is in the case of normal tissues success-
ful only in rather rare instances. In most cases, although some
of the homceo-grafted tissue may remain alive for some time, or
even begin to grow, its growth is soon checked, and it is eventually
absorbed. Certain tumours, however, can be readily grafted from
one animal to another of the same species, and can live and grow in
the new environment.
The difference in the fate of auto- and homoeografts illustrates in a
striking way the important chemical and metabolic differences which
exist, not only between different species, but between individuals of the
same species. In general, a piece of tissue from a rabbit is treated as
an ' unclean ' thing, which must eventually be cast out, not only when
it is introduced into the body of a dog, but when it is introduced into the
body of another rabbit. It is unable to adapt itself to its new en-
vironment, and soon perishes. But a bit of thyroid, of adrenal cortex,
or of uterus, may easily settle down as a successful colonist in very out-
landish places within the body of the animal to which it belongs. An
invasion of lymphocytes, and an ingrowth of fibroblasts, causing develop-
ment of bands of connective tissue, have been regarded by some observers
as the immediate causes of the failure of homoeografts to grow. It is
fully as probable, however, that the lymphocytes gather around and
invade the graft, and that the connective tissue trabeculse appear in it,
because it has already been injured by the antibodies of the host, or, if
not by specific antibodies, then simply by exposure to the more or less
altered metabolic conditions, which it is unable to face successfully.
The difference between the autograft and the homoeograft has not yet
been sufficiently taken account of by surgeons, e.g., in connection with
"44
REPRODUCTION
transfusion of blood. They have slowly learnt that in this case hetero-
grafting (for we can truly call transfusion the grafting of the fluid
tissue blood) is not permissible, and nobody now allows sheep's blood
to pass into the veins of a man. But the danger to the host of repeated
and massive homoeo-transfusions is only beginning to be recognized
by the men who have the power to ' bind and to loose ' veins and arteries.
Some normal organs, e.g., the ovary, are more readily homceografted
than others. Guthrie has shown that hens whose ovaries have been
interchanged are capable of laying eggs. When the hens were im-
pregnated and the eggs hatched out the colour characters of the resulting
offspring seemed to have been influenced, not only by the hen to which
the ovary originally belonged, but also by the hen to which it had been
transferred.
Young have also been obtained from guinea-pigs, whose ovaries had
been replaced by ovaries from other guinea-pigs. Eighteen months
after interchange of the ovaries in two sister puppies, it was shown by
histological examination that the engrafted ovaries contained numerous
normal Graafian follicles, as well as corpora lutea. Statements are on
record of successful ovarian homoeografts even in women.
Another point of great interest in connection with homoeografting
is that a small number of individuals of a species may constitute more
favourable hosts than the great majority for a tissue from another
Fig. 486.— Method of Transplantation (of both Kidneys) in Mass (after Guthrie)
Segments of the inferior vena cava and abdominal aorta are removed with the
kidneys and renal vessels, and interposed in the course of the vena cava and aorta
of another animal, according to the method of Carrel and Guthrie.
individual of the same species. For instance, a rabbit's thyroid
cannot as a rule be successfully grafted into another rabbit, even
when thyroid deficiency has been caused by removal of the greater
part of the thyroid from the host. But if a large number of rabbits
are tried one will occasionally be found in which thyroid homceo-
TRANSPLANTATION OF TISSUES
"45
grafts succeed (Marine and Manley) . It is not as yet known what
the circumstances are which so modify the usual adverse condi-
tions that a homceograft can take, grow and permanently survive.
k. . I
L
*
••
m
\
•
/
J3
11
Fig. 487. — Suturing Bloodvessels: Preliminary Fixation of Ends of Divided Vessels
(after Guthrie). Three fixing ligatures arc placed at equidistant points on the
circumference of the cut ends, each ligature being passed through corresponding
points of the two vessels. The ends of the vessels are approximated by drawing
on the ligatures, which are then tied, and the margins of the vessels sewed together
by continuous stitches in the intervals between the fixing ligatures, as in Fig. 488.
(Carrel's method).
But there is reason to believe that the solution of this problem would
be a long step towards answering the immensely important practical
question what the conditions are which permit the development
of malignant tumours.
Fig. 488. — Suturing Bloodvessels: Method of approximating Ldges aid putting in
Continuous Suture (after Guthrie). The needles are very hut ca ubric sewing-
needles, and the threads single strands of Chinese twist silk or human hair.
Needles and threads are sterilized in paraffin-oil. (Method of Carrel and Guthrie. )
Transplantation of organs may also be done with anastomosis oi
bloodvessels. The main vessels of the engrafted organ are sutured
to suitable arteries and veins in the ' host,' so that the circulation
is at once effective. Consequently there is practically no limit to
the size of the grafts. The kidney, spleen, and even a limb, have
H46 REPRODUCTION
been transplanted in this way from one dog to another. Although
from the operative point of view successful, the homoeo-transplants
do not permanently survive. Reimplantation of organs, however,
in one and the same animal with suturing of the bloodvessels has
often been successfully performed. Such organs as the kidney live
and function after reimplantation, and the operation is now a
recognized physiological method of insuring that an organ has been
completely disconnected from the central nervous system, since even
the nerves running in with the bloodvessels must have been cut.
It has been shown that a reimplanted kidney suffices to maintain a
dog in complete health for an indefinite period after the removal
of the other kidney.
In the case of structures like the large bloodvecsels, which
perform mainly a passive mechanical function, homoeo-transplanta-
tion succeeds. Segments of arteries preserved in cold storage
for a few days or even weeks, and even portions of arteries fixed by
formaldehyde, have been transplanted so as to take the place of
segments removed from arteries of living animals, and have con-
tinued to function perfectly for long periods. Portions of veins
have also been used to fill up gaps in arteries. Even heteroplastic
vascular grafts have been found to succeed, portions of dog's
arteries, e.g., grafted into a cat, and portions of rabbit's, cat's, or
human arteries grafted into a dog. Doubtless the favourable result
is largely due to the fact that the mechanical function of the large
arteries can be discharged even by a dead tube of the requisite
strength, and with the smooth interior presented by a dead endo-
thelial lining (Carrel, Guthrie).
Parabiosis. — Not only may an organ or a portion of tissue from
one individual be engrafted on another, but two individuals may be
so united that a greater or smaller degree of physiological in-
timacy is produced between them. Occasionally, as in the famous
Siamese twins, an anomaly of development results in such close
anatomical union of the circulatory and other systems that in
certain respects the two individuals constitute almost a single
organism, and cannot be separated by surgical interference. A
less intimate union can be established experimentally by opening
the peritoneal cavities of the two animals, and suturing the skin
and connective tissue together so as to permit of permanent
communication. Pairs of animals living in this condition (so-
called parabiosis) have been utilized for the study of certain
questions in immunity. White rats have been kept alive in para-
biosis for as long as thirty-four days in order to test the question
whether destructive antibodies for cancer are present in the circula-
tion (Rous), since it has been shown that circulating antibodies easily
pass from one to the other of such a pair of animals (Ehrlich).
PRACTICAL EXERCISES 1147
One of each pair of rats had a growing tumour produced by
transplantation, while the other had been proved resistant to the
same type of tumour. No evidence of the passage of an antibody
was found in this case.
PRACTICAL EXERCISES.
i. Contractions of Isolated Uterine Rings. — Kill a female adult
rabbit by striking it at the back of the neck. A rabbit which is not
pregnant, or only at the beginning of pregnancy, should be selected.
Open the abdomen, and carefully remove the uterus. While separating
the organ from the broad ligament and vagina, support the horns of
the uterus on soft threads. Ligature the vagina before cutting through
Fig. 489.— Contractions of Rabbit's Uterus Ring. At 41 Ringer's solution was
replaced by adrenalin solution, 1:1,000,000. Time-trace, half-minutes.
it, and cut below the ligature, which can then be used to manipulate
the uterus. Do not pinch the uterus with forceps, and handle it as
little as possible. At once place it in Ringer's or Tyrode's solution*
(p. 200), kept at body temperature (38° C.) in a small beaker immersed
in a water-bath, as in the experiment on the contraction of isolated
intestine (p. 452). Cut a ring of tissue about li centimetres in width
from one of the horns. Tie a loop with a fine silk thread at each end
of a diameter of the ring, pinching up a little of the external coat to do
so with fine forceps. Make the arrangements necessary for recording
contractions of the circular fibres of the ring while it is immersed in a glass
cylinder in the bath, as in Experiment i, p. 452. Connect another tiegment
* Tyrode's solution contains 0-8 gm. NaCl, 0-02 gm. KC1 0-02 gm CaCl
o-oi gm. MgCl2, 0-005 gm. NaH2PO4 o-i gm. NaHCO3 and OT gm. dextrose
ttrt f r\r\ r* /•• *->-f Airo'f/ir'
in too c.c. of water.
1148
REPRODUCTION
longitudinally to a lever as in that experiment, and make all the arrange-
ments mentioned there. After a longer or shorter interval spontaneous
rhythmical contractions of the uterus ring commence. As soon as they
are well established, and while the contractions are being recorded on a
very slow drum, replace the Ringer's solution by serum, defibrinated
blood, blood prevented from coagulating by citrate solution (p. 66), or
hirudin, or by plasma, and note the effect. The serum or plasma may
be diluted to a known amount with Ringer's or Tyrode's solution before
Fig. 490- — At ii Ringer's solution was replaced by citrate plasma. At 39 Ringer's
solution was replaced by hirudin plasma ; at 41 by the corresponding hirudin
serum.
application to the segment. Wash away the serum or plasma thor-
oughly with Ringer's solution. Replace the Ringer's solution by
adrenalin solution (i : 10,000,000). Note whether the tone of the ring
(as shown by its permanent shortening) or the rate and strength of the
contractions are increased. While a tracing is being taken repeat the
observation, adding a larger proportion of adrenalin. Determine in
what concentration a distinct effect is produced. A sufficient number of
uterus rings can be obtained from one animal for a considerable number
of experiments.
PRACTICAL EXERCISES
1149
2. Comparison of Changes of Tone Produced in Uterus Segments by
Different Concentrations of Adrenalin. — For this the uterus of a virgin
rabbit (full-grown or nearly so), is best, as it is advantageous that the
spontaneous contractions should be absent or feeble. Starting always
with the segment* in Ringer's or Tyrode's solution replace the solution
by adrenalin in different dilutions (i : 10,000,000, i : 50,000,000,
i : 1,000,000, etc.), washing off the adrenalin thoroughly with the
Ringer's solution, Compare the effect of serum or defibrinated blood
obtained from the rabbit itself or from some other laboratory animal
with that of a known solution of adrenalin.
If blood collected from the adrenal veins of an animal is available it
should be compared with blood from the same animal taken from the
Fig. 491. — Action on Rabbit's Uterus Segment of Blood Specimens from the Adrenal
Veins (of a Dog) with Different Concentrations of Epinephrin, and Comparison
with Adrenalin added to Blood. At 28 Ringer's solution was replaced by the
second adrenal specimen; at 29 by the third adrenal specimen; at 30 by the fourth
adrenal specimen; at 31 by the fifth adrenal specimen; at 37 by the sixth adrenal
specimen; at 41 by jugular vein blood. All bloods diluted with 15 volumes
Ringer's solution. At 34 adrenalin in jugular blood (i : 2,000,000); at 35 adre.na-
lin in jugular blood (i : 3,000,000); at 36 adrenalin in jugular blood (i : 4,000,000)
replaced Ringer's solution. The adrenalin bloods after being made up to the
concentrations mentioned, were diluted with 15 volumes of Ringer's solution
before application to the segment. (Reduced to one-half.)
general circulation (jugular vein or carotid artery). The tone-increasing
power of the adrenal vein blood will be greater than that of the in-
different blood, because both the serum and the epinephrin will act in
the same sense (Fig. 491).
3. Partition of Adrenalin between Serum and Corpuscles. — Add to
100 c.c. of dog's blood 0-5 c.c. of the 1:1,000 solution of adrenalin.
Centrifuge a portion of the mixture to obtain clear serum. Centrifuge
another portion of the dog's blood to which adrenalin has not been
added. Test on rabbit's uterus segments and also on intestine seg-
* It is best to arrange the segment to record the longitudinal shortening.
1150
REPRODUCTION
merits (p. 453) the defibrinated blood, the serum and the sediment of
corpuscles from the original blood and from the blood to which adrenalin
was added. The adrenalin action of the sediment will be much less
than that of the serum or of the blood (Fig. 492).
Fig. 492. — Action of Adrenalin Defibrinated Blood, Serum and Sediment on Rabbit's
Uterus Segments. At 42 Ringer's solution was replaced by adrenalin blood
serum (i part in 6 parts of Ringer's solution) ; at 43 by the same serum (i in n);
at 44 by the same serum (i in 16); at 52 by the same serum (i in 24); at 51
Ringer's solution was replaced by adrenalin blood (i in 24); at 53 by adrenalin
blood sediment (i in 6); at 54 by the adrenalin blood sediment (i in 24); at 55 by
the ordinary defibrinated blood (i in 6); at 56 by the ordinary defibrinated blood
(i in 24). (Reduced to one-half.)
APPENDIX A
O >MPARISON OF METRICAL WITH ENGLISH MEASURES.
Measures of Length.
I millimetre = 0-03937 inch,
i centimetre =0-39371 ,,
i decimetre = 3-9 3708 inches,
i metre = 39'37O79 ••
i inch = 25-3905 millimetres.
Measures of Weight.
I gramme = 15*432349 grains,
i kilogramme = 2-2046213 pounds.
I ounce = 28-3495 grammes.
I pound =453-5926
Measures of Volume.
i cubic centimetre= 0-061027 cubic inch.
i litre (1,000 cubic centimetres) — 61-027052 cubic inches.
= 1-760773 English or 2-11
American pints.
= 0-22009668 gallon.
i cubic inch = 16-3861759 cubic centimetres.
i cubic foot =28-3153119 cubic decimetres (or litres).
i pint = 0-567932 litre.
i gallon = 4-5434579 litres.
Measures of Work.
i kilogrammetre = about 7-24 foot-pounds.
i foot-pound =0-1381 kilogrammetre.
i (kilo)calorie of heat = 425-5 kilogrammetres of work.
Temperature Scales. — To convert degrees Fahrenheit into degrees
grade, subtract 32, and multiply the remainder by f. To convert
degrees C. into degrees F., multiply by f , and add 32 to the result.
APPENDIX B
BIBLIOGRAPHY.
CHAPTER I.
INTRODUCTION.
Colloids. — BECHOLD, Die Kolloide in Biologic und Medizin, Dresden, 1912,
VAN BEMMELEN, Die Absorption (colloids), Dresden, 1910. BOTAZZI,
Archivio di Fis., 1909, 7, 579- BUXTON and RAHE, Hofmeister's Beit.,
1908, 11, 479; FIELD and TEAGJJP, J. Exp. Med., 1907, 9, 222 (electric
charge of native proteins and agglutinins) . HARDY, J. Phys., 1905-6, 33,
251 (colloidal solution). HEARD, J. Phys., 1912, 45, 27. HOBER,
Hofmeister's Beit., 1908, 11, 64 (neutral salt actions) . PAULI, Hofmeister's
Beit., 1906, 7, 531 J 3, 225. ROBERTSON (T. B.) Die physikalische Chemie
der Proteine, Dresden, 1912. SCHRYVER, Proc. Roy. Soc., 1910, B 83,
96. WALPOLE, J. Phys., 1913, 47, p. xiv.
Coagulation of Proteins. — BUGLIA, Arch. Internat. de Physiol., 1910, 10,
224. CHICK and MARTIN, J. Phys., 1910, 40, 404; 1911, 43, i; 1912, 45,
61, 261. MURRAY (C.), Bioch. J., 1906, 1, 167. RAMSDEN, Proc. Roy.
Soc., 1903, B 72, 156 (surface layers of solutions and suspensions —
mechanical coagulation). SUTHERLAND, J. Phys., 1911, 42, p. vii.
Structure and Aggregate State ol Protoplasm. — CHAMBERS, Am. J. Phys.,
1917, 43, i. JENSEN, Pfliiger's Arch., 1901, 87, 361. HARDY, J. Phys.,
1899, 24, 158, 2o->, KITE, Am. J. Phys., 1913, 32, 146- MATHEWS, B'iol.
, .. Bull. ,1906, 11, 141. RHUMBLER, Z.f. allg. Phys., 1902, 1,279. SCHIFER,
Cju. J. Exp. Phys., 1910, 3, 285. SCHENCK, Pfluger's Arch., 1900,
81, 584. MACALLUM fA. TU ]. Phys 1905, 32, 95 (distribution of K in
cells).
Reaction of Protoplasm. — BARRATT, Brit. Med. J., June 18, 1904, p. 1413.
HENDERSON (L. J.) and BLACK (O. F.), Am. J. Phys., 1907, 18, 250.
Protoplasmic Movement. — JENSEN, -Ergeb. d. Physiol. (Bioph.), 1902, i.
KUHNE, Z. f. Biol., 1897, 35, 43;' ib., 1898, 36, 425. SCHENCK, Pfluger's
Arch., 1897, 66, 241 (oxygen and protoplasmic movement).
Differentiation and Specificity of Starches. — REICHERT (E. T.), Carnegie
Instit. Pub., 1913 (Washington).
Nucleus Plasma Relation. — HOWARD (W. T.), J. Exp. Med., 1908, 10, 207.
Combinations of Proteins and Inorganic Substances.— LOEB (J.), Am. J. Phys.,
1900, 3, 327 (ion-protein compounds). ROBERTSON (T. B.), Ergeb. d!
Physiol., 1910, 216. MANN (G.), Chemistry of the Proteids, London,
1906. PAULI and HANDOWSKY, Hofmeister's Beit., 1908, 11, 415.
Plant Proteins. — OSBORNE (T. B.), Ergeb. d. Phys., 1910, 47; Science 1908
28, 417-
1152
THE CIRCULATING LIQUIDS OF THE BODY 1153
CHAPTER II.
THE CIRCULATING LIQUIDS OF THE BODY.
BUCKMASTER (G. A.), The Morphology of Normal and Pathological Blood,
London, 1906.
Erythrocytes. — DEETJEN, Virchow's Arch., 1901, 165, 282 (envelope}. MEYER,
Arch. Int. Med., 1914, 14, 94 (colour index). ALBRECHT, Zentr. f. Phys.,
1905, 19, 19 (envelope). MEVES, Anat. Anzeig., 23, 212 (structure).
PESKIND, Am. J. Phys., 1903, 8, 414 (action of acids and acid salts).
LSHNER, Arch. Mikros. Anat., 1907, 71, 129 ('membrane' of). Rous
and TURNER, J. Exp. Med., 1916, 23, 219, 239 (living erythrocyles in vitro).
SCHAFER, Anat. Anzeig., 1905, 26 (structure). WEBER and SUCHARD,
Arch, de Phys., ib8o, 12, 521 (rouleaux) . STEWART (G. N.), Am. J.
Phys., 1902, 8, 118 (envelope of Necturus corpuscles).
Blood Formation and Regeneration. — FOOT, J. Exp. Med., 1913, 17, 43
(bone-marrow in vitro). HALL and EUBANK, ib., 1896, 1, 656. NOLL,
Ergeb. d. Phys. (Bioch.), 1903, 433. MALASSEZ, Arch, de Phys., 1882,
i. PEARCE (R. M.) ET AL., J. Exp. Med., 1912, 16, 758, 769, 780 (spleen).
SEEMANN, Ergeb. d. Phys. (Bioch.), 1904, 12. WOOLLEY, J. Lab. Clin.
Med., 1916, 1, 347 (in foetus). OPIE, J. Exp. Med., 1905, 7» 759- SEE-
MANN, Ergeb. d. Phys. (Bioch.), 1904, 30.
Blood at High Altitudes. — ABDERHALDEN, Z. f. BioL, 1902, 43, 125,443;
Pfluger's Arch., 1905, 110, 95. BURKER, ib., 1904, 105, 480. JAQUET,
Arch. Exp. Path. Pharm., 1900, 45, i. SCHNEIDER and HAVENS, Am. J.
Phys., 1915, 36, 380. HENOCCjUE,-Arch. de Phys., 1889, 710. GAULE,
Pfliiger's Arch., 1902, 89, 119. GUILLEMARD and MOOG, J. Phys. Path.
Gen., 1907, 9, 17; ib., 1910, 12, 869.
Destruction of Erythrocytes in the Body.— BAIN, J. Phys., 1903, 29, 352
(rdle of liver and spleen). FINDLAY, ib., 1910, 40, 445 (hcemolysis in the
liver?). KYES, Internat. Monatsch. Anat. Phys., 1914, 31, 543 (in birds).
Rous and ROBERTSON? J. Exp. Med., 1917, 25, 651, 665.
Variation in Number of Erythrocytes. — BOOTHBY and PERRY, Am. J. Phys.,
1915, 37, 378. HAWK, ib., 1904, 10, 384 (effect of exercise). BURKER,
Pfliiger's Arch., 1905, 107, 426 (technique). DOWNS and EDDY, Am. J.
Phys., 1917, 43, 415 (influence of secretin). HASSELBALCH and HEYERDAHL,
Skand. Arch. Phys., 1908, 20, 289 (some physical causes of variation).
WARD, Am. J. Phys., 1904, 11, 394. WELLS (J. J.) and SUTTON (J. E.),
Am. J. Phys., 1915, 39, 31 (blood counts in frog, turtle and mammals).
(For influence of Adrenalin see Chapter XI.)
Permeability of Erythrocytes. — DE BOER, J. Phys., 1917, 51, 211 (influence
of respiration on exchange of SO4 between corpuscles and plasma) . HAM-
BURGER, Osmotischer Druck und lonenlehre; Bioch. Z., 1915, 71, 464
(influence of osmotic pressure and the permeability problem) ; Z. f . Physikal.
Ch., 1909, 69, 663 (for Ca ions). HO^ER, Pfluger's Arch., 1904, 102, 196;
Oppenheimer's Handb. d. Bioch., 1908, 2, i. MASING, Pfliiger's Arch.,
1913, 149, 227 (glucose). MANWARING and KUSAMA, Soc. Exp. Biol.
Med., 1916, 13, 17/5 (for protein). ROHONYI, Kolloid. Chem. Beihefte,
1916, 8, 337, 377 (Physiol. Abstracts, 1917, 2, 178, 179). SPIRO and
HENDERSON, Bioch. Z., 1908, 15, 114 (influence ofCOz).
Osmotic Relations of Erythrocytes. — BANG, Bioch. Z., 1909, 16, 255.
EYKMAN, Pfluger's Arch., 1897, 68, 58 (permeability). HEDIN, ib., 68,
229 (permeability). HOBER, ib., 1904, 102. 196 (ion-permeability).
GRYNS, ib., 1896, 63, 86; ib., 1905, 109, 289. HAMBURGER, Z. f. Biol.,
1897, 35, 252, 289 (respiratory exchange and volume of erythrocytes) .
KORANYI and BENCE, Pfluger's Arch., 1905, 110, 532 (action of CO2).
KOEPPE, ib., 1897, 67, 189. MOORE and ROAF, Bioch. J., 1907, 3, 55.
SCOTT (F. H.), J. Phys., 1915, 50, 128. STEWART (G. N.), J. Phys.,
1900-1, 26, 470.
73
1 154 BIBLIOGRAPHY
Resistance of Erythrocytes. — CHALIER and CHARLET, J. Phys. Path. Gen.,
191 1, 13, 728 (effect of splenectomy). HAMBURGER (H. J.), ib., 1900, 2,
889. HILL (L. V.), Arch. Int. Med., 1915, 16, 809 (in the ancemias, etc.).
MUSSER and KRUMBHAAR, J. Am. Med. Ass., 1916, 67, 1894.
Haemolysis. — ARRHENIUS, Bioch. Z., 1908, 11, 161; Ergeb. d. Phys., 1908,
480. BASHFORD, Arch, de Pharmacodyn., 8, 101 ; 9, 451 (blood immunity) .
BAUMGARTEN, Bioch. Z., 1908, 11, 21 (osmological theory). BORDET,
Ann. Instit. Pasteur, 1900, 14, 257; BORDET and GAY, ib., 1908, 22
(hcemolytic sera). EHRLICH, Proc. Roy. Soc., 1906, B 66 ; Berl. Klin. Woch.
(numerous papers from 1899 onwards). FLEXNER and NOGUCHI, J. Exp.
Med., 6, 277; KYES, Berl. Klin. Woch., 1903, Nos. 42, 43; Bioch. Z.,
I9°7, 4, 99; J. Infect. Dis., 1910, 7, 181; MITCHELL and REICHERT,
Smithson. Contrib., 1886, 9 (venom h&molysis). GUTHRIE (C. C.), Am.
J. Phys., 1903, 8, 441 ; J. Lab. Clin. Med., 1917, 3, 87; GUTHRIE and LEE,
Soc. Exp. Biol. Med., 1914, 11, 149 (taking by hypertonic solutions).
JOBLING and BULL, J. Exp. Med., 1913, 17, 61 (relation of immune serum
lipase to hesmolysis). KRAUS and LEVADITI, Handb. d. Tech. u. Method,
d. Immunitatsforschung, 1, 57; 2, 903. MCPHEDRAN, J. Exp. Med.,
1913, 18, 527 (acids and hcemolysis). MANWARING, Brit. Med. J., 1906,
2, 1542; J. Inf. Dis., 1907, 4 (physical chemistry of hcemolytic serum);
J. Biol. Ch., 1907, 3, 387 (quantitative methods). MELTZER and WELCH,
J. Phys., 1884-5, 5, 255 (shaking). NOGUCHI, Bioch. Z., 1907, 6, 185.
TRAUBE, Bioch. Z., 1908, 10, 371; Pfluger's Arch., 1904, 105, 541, 559
(lipoids and hezmolysis). PESKIND (S.), Am. J. Phys., 1904, 12, 184
(ether laking). ROAF, Q. J. Exp. Phys., 1912, 5, 132 (taking by alkali,
hypotonic NaCl, heat). STEWART (G. N.), J. Pharm. Exp. Ther., 1909,
1, 49 (mechanism of hamolysis) ; Am. J. Phys., 1902, 8, 103 (nucleated
corpuscles); ib., 1903, 9, 72 (influence of cold) ; ib., 1904, 11, 250; 12, 363
(hcemolysinogenic and agglutininogenic action of laked corpuscles) ; J. Med.
Res., 1902, 8, 268; J. Phys., 1900-1, 26, 470. WASSERMANN, Immune
Sera (translated by Bolduan).
Cytolysins. — LAMBERT, J. Exp. Med., 1913, 19, 377. TAYLOR, J. Biol. Ch.,
1908, 5, 311.
Leucocytes.- — BUSCH and VAN BERGEN, J. Med. Res., 1902, 8, 408; ib., 1903,
10, 250 (differential count in dog and cat). DEETJEN, Arch. f. Phys., 1906
401 (division of human leucocytes in vitro). EVANS (F. A.), Arch. Int.
Med., 1916, 18, 692 (mononuclear) . HARDY and WESBROOK, J. Phys.,
1895, 18, 490. HAMBURGER (H. J.), Arch. f. Phys., 1902, Supp. Bd.,
119 (permeability of leucocytes). KANTHACK and HARDY, J. Phys.,
1894-5, 17, 81 (wandering cells of mammalia). HOWE and HAWK, Am. J.
Phys., 1912, 30, 174 (differential count during fasting). EHRLICH and
LAZARUS, The Histology of Blood, Normal and Pathological. Ross
(H. C.), J. Phys., 1908, 37, 327 (death of leucocytes). WALKER (C. E.),
Proc. Roy. Soc. (Lond.), 1906, B78, 53 ; ib., 1907, 79, 491, 495 (life history).
Blood-Platelets. — BROWN (W. H.), J. Exp. Med., 1913, 18,275 (histogenesis) .
BURKER, Pfluger's Arch., 1904, 102, 36 (in coagulation). BUNTING, J. Exp.
Med., 1909, 11, 541. BAYNE- JONES, Am. J. Phys., 1912, 30, 74 (pro-
thrombin and thromboplastin) . DEETJEN, Z. f. Physiol. Ch., 1909, 63, I.
DUKE, Arch. Int. Med., 1913, 11, 100; J.Am. Med. Ass., 1915, 65, 1600
(cause of variations in platelet count). EMMEL (V. E.), J. Med. Res., 1917,
37, 67 (erythrocytic origin). LEE and MINOT, J. Am. Med. Ass., Apr. 21,
1917, I2ii (significance). — LE SOURD and PAGNIEZ, J. Phys. Path. Gen.,
1909, 11, i (in coagulation); ib., 1912, 14, 1167 (in regeneration of blood) .
MINOT, Arch. Int. Med., 1917, 19, 1062 (in purpura, etc.). ZUCKER and
STEWART, Zentralb. f. Phys., 1913, 27, 85 (platelets and the vasoconstrictor
property of serum). KEMP and CALHOUN, Am. J. Phys., 1901, 5, iv.
WRIGHT (J. H.) and MINOT, J. Exp. Med., 1917, 26, 395. ZUCKER (T. F.),
Soc. Exp. Biol. Med., 1914, 11, 60 (platelets and clotting).
Viscosity of Blood. — BURTOX-OPITZ, J. Exp. Med., 1906, 8, 59, 240; J. Phys.,
1904-5, 32, 385; J. Am. Med. Ass., 1911, 57, 353; Am. J. Phys., 1914/35,
THE CIRCULATING LIQUIDS OF THE BODY 1155
51, 265. DENNING and WATSON, Proc. Roy. Soc., 1906, B 78, 328.
HttRTHLE, 1900, Pflilger's Arch., 82, 415. SNYDER and TODD, Am.
J. Phys., 1911, 28, 161.
Reaction of Blood. — ADLER, Am. J. Phys., 1907, 19, i. CULLEN, J. Biol.
Ch., 1917, 30, 369. HASSELBALCH and LUNDSGAARD, Skand. Arch. Phys.,
1912, 27, 13 ; Bioch. Z., 1912, 38, 77; ib., 41, 247 (effect ofCO2). MILROY,
Q. J. Exp. Phys., 1915, 8, 141; J. Phys., 1917, 51, 259. MCCLENDON,
J. Biol. Ch., 1916, 24, 519; ib., 25, 669 (method). PARSONS (T. R.), J.
Phys., 1917, 51, 440. SCOTT (R. V.), J. Lab. Clin. Med., 1916, 1, 608
(dissociation curve as index of H-ion concentration). PETERS, Am. J.
Phys., 1917, 43, 113 (COo). LEVY, ROWNTREE and MARRIOTT, Arch.
Int. Med., 1915, 16, 389. ROBERTSON, J. Biol. Ch., 1909, 7, 351-
Regulation of Reaction. — HENDERSON (L. J.) and BLACK (O. F.), Am. J.
Phys., 1908, 21, 420. HENDERSON, ib., 21, 173, 427; ib., 1907, 18, 250;
Ergeb. d. Phys., 1909, 254 ; J. Biol. Ch., 1909, 7, 29. MOORE and BIGLAND,
Bioch. J., 1909, 5, 32. McCLENDON ET AL., J. Biol. Chem., 1917, 31,
519. ROBERTSON, ib., 1909, 6, 313.
Relative Volume of Corpuscles and Plasma. — BLEIBTREU, Pfliiger's Arch.-
1892, 51, 151; ib., 1895, 60, 405. CAPPS, J. Med. Res., 1903, 10, 367
(volume index). FRAENCKEL (P.), Z. f. Klin. Med., 1904, 52, 470; STEWART
(G. N.), J. Phys., 1899, 24, 356 (electrical resistance method). HEDIN,
Pfliiger's Arch., 1895, 60, 360; KOEPPE, ib., 1905, 107, 187 (hematocrit) .
LARRABEE, J. Med. Res., 1911, 24, 15 (volume index).
Electrical Conductivity of Blood.— BRUNINGS, Pfluger's Arch., 1903, 100.
393. H6BER, Physikal. Chem. d. Zelte. HAMBURGER, Osmotischer
Druck. FRANK, Am. J. Phys., 1905, 14, 466 (during coagulation).
OKER-BLOM, Pfliiger's Arch., 1900, 81, 167. STEWART (G. N.), J. Phys.,
1899, 24, 211. WILSON (T. P.), Am. J. Phys., 1905, 13, 139; Bioch. J.,
1907, 2, 377 (in coagulation).
Blood-Coagulation. — ARTHUS, J. Phys. Path. Gen., 1901, 3, 887 (fluoride);
ib., 1902, 4, i, 281; Arch, de Phys., 1890, 22, 79. COLLINWOOD and
MACMAHON, J. Phys., 1912, 45, 119. CRAMER and PRINGLE, Q. J. Exp.
Phys., 1913, 6, i ; J. Phys., 1912, 45, p. xi. DELEZENNE, J. Phys. Path. Gen.,
I897, 333, 347 (bird's blood). HOWELL, Am. J. Phys., 1911, 29, 187
(antitkrombin) ; ib., 1914, 35, 143 (ultramicroscope) ; ib., 1916, 40, 526.
LOEB (L.), Hofmeister's Beit., 1907, 9, 185. LOEB and FLEISCHER, Bioch.
Z., 1910, 28, 169 (coagulins). MELLANBY, J. Phys., 1908, 38, 28. PICK
and SPIRO, Z. Physiol. Ch., 1900, 31, 235 (proteases). MORAWITZ, Ergeb.
d. Phys., 1905, 307; Deutsch. Arch. Klin. Med., 1903-4, pp. i, 215, 432.
REICHERT, J. Exp. Med., 1905, 7, 173 (second coagulation). RETTGER,
Am. J. Phys., 1909, 24, 406. DASTRE and FLORESCO, Arch, de Phys.,
1896, 402. STUEBEL, Pfliiger's Arch., 1914, 156, 361 (ultramicroscope).
Coagulation Time. — ADDIS, Q. J. Exp. Phys., 1908, 1, 305. BURKER, Pfliiger's
Arch., 1913, 149, 318. CANNON and GRAY, Am. J. Phys., 1914, 34, 232.
CANNON and MENDENHALL, ib., 1914, 34, 243 (adrenalin effect). SIMPSON
and RASMUSSEN, Q. J. Exp. Phys., 1916, 10, 159.
Calcium and Coagulation. — ARTHUS, Arch, de Phys., 1896, 47; ib., 1897, 219.
AUSTIN and PEPPER, Arch. Int. Med., 1913, 11, 305. ADDIS, Q. J. Exp.
Med., 1909, 2, 149. BEARD, J. Phys., 1917, 51, 294. HESS, Soc. Exp.
Biol. Med., 1916, 13, 59. GODDARD, Am. J. Phys., 1914, 35, 333.
MORAWITZ, Hofmeister's Beit., 1904, 4, 381. RICH, Am. J. Phys., 1917,
43,371-
Anticoagulants. — FRANZ (F.), Arch. Exp. Path. Pharm., 1903, 49, 342 (hirudin).
HAYCRAFT, ib., 1884, 18, 209 (leech extract). LEE and VINCENT, J. Med.
Res., 1915, 32, 445 (anaphylaxis and leech extract). MELLANBY (J.),
J. Phys., 1909, 38, 441 (venoms). MINOT, Am. J. Phys., 1915, 39, 131
(chloroform). PRINGLE and TAIT, J. Phys., 1910, 40, p. xxxv. ; ib., 1911,
42, p. xxxviii. SHATTUCK, Arch. Int. Med., 1917, 20, 167 (protein
intoxication) .
1 156 BIBLIOGRAPHY
Proteoses and Blood-Coagulation.— ARTHUS and HUBER, Arch, de Phys., 1896,
857. DASTRE and FLORESCO, ib., 1897, 210. DELEZENNE, ib., 1895, 8,
655; ib., 1898, 568 (relation of liver). GLEY and PACHON, ib., 1896,715
(liver). PICK and SPIRO, Z. Physiol. Ch., 1900, 31, 235. SCHMIDT-
MULHEIM, Arch. f. Phys., 1880, 33.
Fibrin, Fibrinogen. — HOWELL, Am. J. Phys., 1916, 40, 526 (fibrin-gel and
theories of gel -formation). MORAWITZ, Oppenheimer's Handb. d. Bioch.,
ii., 2, 60.
Origin of Fibrinogen. — GOODPASTURE, Am. J. Phys., 1914, 33, 70. MATHEWS
(A. P.), ib., 1899, 3, 53- MEEK, ib., 1912, 30, 161 (liver). OPIE, BARKER
and DOCHEZ, J. Exp. Med., 1911, 13, 162. WHIPPLE, Am. J. Phys.,
1914, 33, 50.
Thrombin, etc. — COLLINWOOD and MACMAHON, J. Phys., 1913-14, 47, 44
(thrombin and antithrombln) . GASSER, Am. J. Phys., 1917, 42, 378
(significance of prothrombin and thrombin in serum). HOWELL, Am. J.
Phys., 1914, 35, 474 (prothrombin). DRINKER (C. K. and K. R.), ib.,
1916, 41, 5 (prothrombin from bone-marrow). MINOT and DENNY, Arch.
Int. Med., 1916, 17, 101 (prothrombin and antithrombin factors in coagu-
lation). RICH, Am. J. Phys., 1917, 43, 549 (metathrombi n) . MELLANBY
(J.), J. Phys., 1917, 51, 396 (rate of formation from prothrombin).
Antithrombin. — DENNY and MINOT, Am. J. Phys., 1915, 38, 233. HESS,
J. Exp. Med., 1915, 21, 338.
Thromboplastic Substances in Coagulation. — HOWELL, Am. J. Phys., 1912,
31, i. MACRAE and SCHNACK, ib., 1913, 32, 211 (action in clotting).
McLEAN, ib., 1916, 41, 250; ib., 1917, 43, 586 (cepfialin).
Intravascular Coagulation. — DAVIS, Am. J. Phys., 1911, 29, 160. HALLI-
BURTON and BRODIE. J. Phys., 1894, 17, 135. MUDGE, Proc. Roy. Soc.
(Lond.), 1907, B 79, 103. PICKERING, J. Phys., 1896, 20, ?io (albinos).
WRIGHT (A. E.), J. Phys., 1891, 12, 184.
Coagulation in Invertebrates. — ALSBERG and CLARK, J. Biol. Ch., 1908, 5, 323
(limulus). LOEB (L.), Bioch. Z., 1910, 24, 478. TAIT, Q. J. Exp. Phys.,
1910, 3, i.
Blood-Proteins. — BRIGGS, J. Biol. Ch., 1915, 20, 7. CULLEN and VAN SLYKE,
Soc. Exp. Biol. Med., 1916, 13, 197 (methods). EPSTEIN, J. Exp. Med.,
1913, 17, 444. PORGES and SPIRO, Hofmeister's Beit., 1903, 3, 277
(globulins). ROBERTSON, J. Biol. Ch., 1912, 13, 325. THOMPSON, ib.,
1915, 20, i. WELLS, ib., 1913, 15, 37. WOOLSEY, ib., 1913, 14, 433.
HAMMARSTEN, Ergeb. d. Phys. (Bioch.), 1902, 330. MELLANBY (J.), J.
Phys., 1907-8, 36, 288.
Blood-Lipoids. — BLOOR, J. Biol. Ch., 1916, 25, 577 (man). BROWN (E. W.),
Am. J. Phys., 1899, 2, 306 (cholesterol in birds). JOSLIN, BLOOR and
GRAY, J. Am. Med. Ass., 1917, 69, 375; SEO, Arch. Exp. Path. Pharm.,
1909, 61, i (diabetes).
Cholesterol in Blood. — BLOOR, J. Biol. Ch., 1916, 24, 227; ib., 1917, 29, 437.
CSONKA, ib., 1916, 24, 431. GORHAM and MYERS, Arch. Int. Med., 1917,
20, 599- WESTON And KENT, J. Med. Res., 1912, 26, 531.
Blood-Fat. — BLOOR, J. Biol. Ch., 1914, 19, i. TERROINE, J. Phys. Path. Gen.,
1914, 16, 212.
Serum Ferments. — BRONFENBRENNER and SCOTT, Soc. Exp. Biol. Med.,
1915, 12, 137. JOBLING, PETERSEN and EGGSTEIN, J. Lab. Clin. Med.,
1916, 1, 172; J. Exp. Med., 1915, 22, 129, 568. SLOAN, Am. J. Phys.,
1915, 39, 9. CARLSON and LUCKHARDT, Am. J. Phys., 1908, 23, 148.
GOULD and CARLSON, ib., 1911, 29, 165; OTTEN and GALLOWAY, ib., 1910,
26, 347 (relation of pancreas to serum diastase). KING, ib., 1914, 35, 301.
VAN DER ERVE, ib., 1911, 29, 182 (diastatic enzymes in serum).
Vasoconstrictor Property of Serum. — ATKINSON and FITZPATRICK, Soc. Exp.
Biol. Med., 1912, 9, 49. CrsHNY and GUNN, J. Pharm. Exp. Ther.,
1913, 5, i (action of serum on perfused heart). O'CONNOR (J. M.), Arch.
THE CIRCULATING LIQUIDS OF THE BODY 115?
Exp. Path. Pharm., 1912, 67, 195- STEWART (H. A.) and HARVEY
(S. C.), J. Exp. Med., 1912, 16, 103. STEWART (G. N.) and ZUCKER,
j. Exp. Med., 1913, 17, 152. TATUM, J. Pharm. Exp. Ther., 1912,4, 115-
Anaphylactic or Protein Shock. — ANDERSON and SCHULTZ, Soc. Exp. Biol,
Med., 1910, 7, 32. AUER and ROBINSON, J. Exp. Med., 1913, 18, 450,
556. EISENBREY and PEARCE, J. Pharm. Exp. Ther., 1912, 4, 21.
JOBLING, PETERSEN and EGGSTEIN, J. Exp. Med., 1915, 22, 401 (ferment
actions). MANWARING and CROWE, J. Immunity, 1917, 2, 517; VOEGTLIN
and BERNHEIM, J. Pharm. Exp. Ther., 1911, 2, 507; WEIL, J. Immunity,
JQi/, 2, 525 (relation of liver to). WEIL, ib., 1917, 2, 429 (the vasomotor
depression in).
Haemoglobin and Derivatives. — BARCROFT and HILL, J. Phys., 1910, 39, 411
(nature of oxyhcemoglobin, molecular weight). HUFNER and GANSSER,
Arch. f. Phys., 1907, 209 (molecular weight). FISCHER (H.), Ergeb. d.
Phys., 1916, 185, 791 (blood and bile pigments). HALDANE, J. Phys.,
1900-1, 26, 497 (colorimetric determination); ib., 1898, 22, 298 (methamo-
globin). HARTLEY, J. Phys., 1907, 36, 62 (sulphhcvmoglobin). ALSBERG
and CLARK, J. Biol. Ch., 1910, 8, i; ALSBERG, ib., 1915, 23, 495 (hamo-
cyanin). MENZIES, J. Phys., 1895, 17, 402 (met hemoglobin). MILROY
(J. A.), J. Phys., 1909, 38, 384 (hcemochromogen); ib., 1909, 38, 392;
MENZIES, ib., 1914, 49, p. iv. (hcemalin). LAIDLAW, ib., 1904, 31, 464
(synthesis of heemalin). REICHERT, Am. J. Phys., 1903, 9, 97. REICHERT
and BROWN, Soc. Exp. Biol. Med., 1907-8, 5, 66; Proc. Am. Phil. Soc.
(Philadelphia), 1908, 47, 298. FRIEBOES, Pfliiger's Arch., 1903, 98, 434
(hemoglobin crystals).
Quantity of Blood. — DOUGLAS, J. Phys., 1905-6, 33, 493; ib., 1910, 40, 472.
HALDANE and SMITH, J. Phys., 1899-1900, 25, 331; SMITH (J. LORRAIN),
ib., p. vi. (CO method). DREYER (G.), RAY and WALKER, Skand. Arch.
Phys., 1913, 28, 299. KEITH, ROWNTREE and GERAGHTY, Arch. Int.
Med., 1915, 16, 547. PLESCH, Z. Exp. Path. Ther., 1909, 6, 380. ZUNTZ
and PLESCH, Bioch. Z., 1908, 11, 47.
Vividiffusion. — ABEL, ROWNTREE and TURNER, J. Pharm. Exp. Ther., 1914,
5, 275. ROHDE (A.), J. Biol. Ch., 1915, 21, 325 (ammonia of the circulating
blood).
Lymph. — CARLSON, GREER and LUCKHARDT, Am. J. Phys., 1908, 22, 91
(chlorides). CARLSON, WOELFEL and POWELL, ib., 1911, 28, 176 (local
hcBmodynamic action of tissue metabolites). GREEN (J. R.), ib., 1910,
26, 68; Rous, J. Exp. Med., 1908, 10, 537 (leucocytes). DAVIS and
PETERSEN, J. Exp. Med., 1917, 26, 693 (ferments). Ho WELL, Am. J.
Phys., 1914, 35, 483; LUSSKY, ib., 25, 354 (coagulation). HUGHES and
CARLSON, Am. J. Phys., 1908, 21, 236 (hcemolytic action). LUCKHARDT,
ib., 1910, 25, 345 (conductivity compared with serum).
Chyle.— HALL (W. S.), J. Am. Med. Ass., 1910, 55, 388. HAMILL, J. Phys.,
1906-7, 35, 151. PATON (D. NOEL), j. Phys., 1890, 11, in. SOLLMANN,
Am. J. Phys., 1907, 17, 487.
CHAPTER III.
THE CIRCULATION OF THE BLOOD AND LYMPH.
CARLSON, Biol. Bull., 1905, 8,123 (comparative physiology of invertebrate heart).
MACWILLIAM, J. Phys., 1885, 6, 192 (heart of eel); ib., 1888, 9, 167
(rhythm of mammalian heart). NUKADA (S.), Die Automatic und Koordi-
nation des Herzens, Tokyo, 1917 (limulus heart). ROY and ADAMI,
Phil. Trans. Roy. Soc., 1892, 183, 199 (physiology and pathology of heart).
TIGERSTEDT, Kreislauf . WIGGERS, The Circulation in Health and Disease,
1158 BIBLIOGRAPHY
Cardiac Cycle. — BACHMANN, Am. J. Phys., 1916, 41, 309 (inter auricular
interval}. WIGGERS, ib., 1916, 40, 218 (auricular myogram); ib., 1916,
42, 141 (events of auricular systole). HAYCRAFT and PATERSON, J. Phys.,
1895-6, 19, 496 (changes in heart's shape and position) ; ib., 262 (papillary
muscles). TUNNICLIFFE, ib., 1896, 20, 51 (diastole).
Heart Sounds. — BATTAERD, Heart, 1915, 6, 121 (graphic researches). BRIDG-
MAN, Heart, 1915, 6, 41. EINTHOVEN, Pfliiger's Arch., 1907, 120, 31.
SEWALL, Phila. Monthly Med. J., Sep., 1899 (papillary muscles). THAYER,
Arch. Int. Med., 1909, 4, 297 (third heart-sound). WIGGERS and DEAN,
Am. J. Phys., 1917, 42, 476 (nature of time relations).
Registration of Heart Sounds. — CREHORE and MEARA, J. Exp. Med., 1911,
13, 616 (micrograph). EINTHOVEN, Pfliiger's Arch., 1907, 117, 461.
HOLOWINSKI, Arch, de Phys., 1896, 823. HURTHLE, Pfliiger's Arch.,
1895,60,263. WEISS (O.), Phono-kardiogramme (Jena, 1909). WIGGERS
and DEAN, Am. J. Med. Sci., 1917, 153, 666.
Heart Rate. — BAINBRIDGE, J. Phys., 1915, 50, 65 (influence of venous filling on
rale). BUCHANAN (F.), ib., 1910, 40, p. xlii (in hibernation); ib., 1908,
37, p. Ixxix (in mouse); Sci. Progress, July, 1910 (in vertebrates). LOEB
and EWALD, Bioch. Z., 1913, 58, 177 (heart-rate as function of the
temperature).
Function of Pericardium. — BARNARD (H. L.), J. Phys., 1898, 22, p. xliii.
KUNO (Y.), ib., 1915, 50, i.
Endocardiac Pressure: Auricle. — WIGGERS, Am. J. Phys., 1914, 33, 13.
ZWALUWENBURG and AGNEW, Heart, 1912, 3, 343.
Endocardiac Pressure: Ventricle. — FRANK (O.), Z. f. Biol., 1897, 35, 478.
FRANCIS-FRANK, Arch, de Phys., 1890, 22, 395; ib., 1893, 25, 83.
PORTER, J. Exp. Med., 1896, 1, 296. TIGERSTEDT, Skand. Arch. Phys.,
1912, 28, 37; ib., 1914, 31, 241. WIGGERS, Am. J. Phys., 1914, 33, 382.
Coronary Circulation. — BARBOUR and PRINCE, J. Exp. Med., 1915, 21, 330
(epinephrin) . GUTHRIE and PIKE, Science, 1906, 24, 52 (coronary pressure
and action of heart). HYDE, Am. J. Phys., 1, 215 (dilation of ventricles
and coronary flow). LANGENDORFF, Pfliiger's Arch., 1899, 78, 423
(isolated heart). MAGRATH and KENNEDY, J. Exp. Med., 1897, 2, 13
(coronary circulation and ventricular beat). MARKWALDER and STARLING,
J. Phys., 1913, 47, 275. MILLER and MATTHEWS, Arch. Int. Med., 1909,
3, 476 (obstruction of left coronary). PORTER, J. Exp. Med., 1895, 1, 46
(closure of coronaries) ; Am. J. Phys., 1, 145 (influence of beat on coronary
flow).
PULSE.
Arterial Pulse. — DAWSON (P. M.), Am. J. Phys., 1917, 42, 613 (pulse velocity).
FRANK (O.), Z. f. Biol., 1899, 37, 483 (mathematical); ib., 1905, 46, 441.
HEWLETT, Arch. Int. Med., 1914, 14, 609 (reflection of primary wave).
HILL, BARNARD and SEQUEIRA, J. Phys., 1897, 21, 147 (effect of venous
pressure). HOORWEG, Pfliiger's Arch., 1905, 110, 598 (peripheral reflection).
HORTHLE, Pfliiger's Arch., 1890, 47, 17 (origin of secondary waves).
LEWIS (T.), J. Phys., 1906, 34, 414. LOHMAN, Pfliiger's Arch., 1904, 103,
632 (dicrotic wave). MACWILLIAM, KESSON and MELVIN, Heart, 1913,
4, 393 (conduction of pulse wave). TIGERSTEDT, Ergeb. d. Phys., 1909, 593.
WIGGERS, J. Am. Med. Ass., 1915, 64, 1483 (contour of normal pulse) .
Venous Pulse. — CUSHNY and GROSH, J. Am. Med. Ass., 1907, 49, 1254.
EWING, Am. J. Phys., 1914, 33, 158. EYSTER, J. Exp. Med., 1911, 14,
594; ib., 1910, 12, 257. FREDERICO,, Zentralb. f. Phys., 1908, 22, 297.
MCQUEEN and FALCONER, J. Phys., 1914, 48, 292 (' C ' wave). MORROW,
Brit. Med. J., Oct. 27, and Dec. 22, 1906; Pfliiger's Arch., 1900, 79,
442 (velocity). WIGGERS, J. Am. Med. Ass., 1915, 64, 1483.
Cardiopneumatic Movements. — HARRIS, J. Phys., 1905, 32, 495- HAYCRAFT,
ib., 1891, 12, 426. MELTZER, Am. J. Phys., 1898, 1, 117. STEWART
(G. N.), Arch. f. Phys., 1912, 460.
THE CIRCULATION OF THE BLOOD AtfD LYMPH 1159
BLOOD-PRESSURE.
Arterial Blood-Pressure. — BROOKS, Heart, 1910, 2, 5 (tracings from quiescent
animal). CAMPBELL (H.), J. Phys., 1898-9, 23, 301 (place of chief resist-
ance to flow). DAWSON, Am. J. Phys., 1906, 15, 244 (pressure at different
points of arterial tree). FRANK (O.), Z. f- Biol., 1907, 50, 281 (elastic
membranes). HURTHLE, Pfluger's Arch., 1905, 110, 421; ib., 1912, 147,
509 (pressure and velocity). MAC€RAKEN and WERNESS, J. Pharm.,
Exp. Therap., 1917, 9, 305 (overcoming clotting). PILCHER, Am. J. Phys.,
1915, 38, 209 (membrane manometer curves). RIDDLE and MATTHEWS,
Am. J. Phys., 1907, 19, 108 (birds). WIGGERS, ib., 1914, 33, i (pressure
curve in pulmonary artery). WOOD (H. C.), ib., 1899, 2, 352 (traube
waves). WOOLEY, J. Lab. Clin. Med., 1915, 1, 203 (CO^and blood-pressure).
Action of Proteoses on Blood-Pressure (and Coagulation). — CHITTENDEN,
MENDEL and HENDERSON, Am. J. Phys., 1899, 2, 142. PEARCE (R. M.)
and EISENBREY, Arch. Int. Med., 1910, 6, 218. THOMPSON, J. Phys.,
1896, 20, 455; 1899, 24, 374. UNDERBILL, Am. J. Phys., 1903, 9, 345.
ZUNZ, Arch. Int. de Phys., 1911, 11, 73. See also under Chapter II.
(proteoses and coagulation).
Arterial Blood-Pressure in Man. — BORACH and MARKS, Arch. Int. Med., 1913,
11, 485; ib., 1914, 13, 648. ELLIOTT (B. L.), Am. J. Phys., 1917, 42, 290
(effect of occlusion of bloodvessels). ERLANGER and HOOKER, Johns
Hopkins Hosp. Rep., 1904, 12, 145. HILL and ROWLANDS, Heart, 1912,
3, 219. LOMBARD, Am. J. Phys., 1912, 29, 335 (skin). McCuRDY, Am.
J. Phys., 1901, 5, 95 (exerffise). MULLER (F.), Harvey Lecture, New York,
1907. ROLLESTON, Heart, 1912,4,83 (in-aortic incompetence) . TAUSSIG,
Arch. Int. Med., 1913, 11, 542.
Measurement of Blood-Pressure in Man. — FRANK (O.), Tigerstedt's Handbuch
d. physiol. Methodik, 2, Abth. 4, 216. MACLEOD. J. Lab. Clin. Med.,
1915. 1» 62, 138 (resume).
Auscultatory Method. — BROOKS and LUCKHARDT, Am. J. Phys., 1916, 40, 49.
ERLANGER, ib., 40, 83. FOLEY, COBLENTZ and SNYDER, ib., 40, 5.54.
HILL (L.), Heart, 1909, 1, 73. HOOKER and SOUTHWORTH, Arch. Int.
Med., 1914, 13, 384. KILGORE, Arch. Int. Med., 1915, 16, 927. MAC-
WILLIAM and MELVIN, Heart, 1914, 5, 153. WARFIELD, Arch. Int. Med.,
1912, 10, 258. WIGGERS, J. Am. Med. Ass., 1915, 64, 1485 (segment
capsules, optical record).
Oscillatory Method. — ERLANGER, Johns Hopkins Hosp. Rep., 1904, 12, 53 ;
Am. J. Phys., 1908, 21, p. xxiv. KILGORE, Arch. Int. Med., 1915, 16, 893.
Venous Pressure. — BURTON-OPITZ, Am. J. Phys., 1903, 9, 198. HOOKER, ib.,
1914, 35, 73; ib., 1916, 40, 43. v. RECKLINGHAUSEN, Arch. Exp. Path.
Pharm., 1906, 55, 470. SEWALL, J. Am. Med. Ass., 1906, 47, 1279.
RATE OP PERIPHERAL BLOOD-FLOW.
BURTON-OPITZ, Am. J. Phys., 1914, 38, 64 (carotid) ; Quart. J. Exp. Phys.,
1910, 3, 297; ib., 1911, 4, 93; ib., 1912, 5, 83 (hepatic artery); ib., 1911,
4, 113; ib., 1912, 5, 189; ib., 1912, 5, 309 (portal vein). BRODIE and
RUSSELL, J. Phys., 1905, 32, p. xlvii.
Blood-Flow in Man. — EDMUNDS, Am. J. Phys., 1907, 18, 129 (influence of
drugs on velocity). FRANK (O.), Z. f. Biol., 1898, 37, I (velocity, Pitot's
tubes). HEWLETT and VAN ZWALUWENBURG, Heart, 1909,1,87 (arm);
Am. J. Med. Sci., 1913, 145, 656; Arch. Int. Med., 1911, 8, 591. HOUGH
and BALLANTYNE, J. Bost. Soc. Med. Sci., June, 1899 (skin, influence of
temperature). MACLEOD, J. Lab. Clin. Med., 1916, 1, 359 (resume).
MACLEOD and PEAltcli, Am. J. Phys., 1914, 35, 87 (liver). MATAS, J. Am.
Med. Ass., 1914, 63, 1441 (collateral circulation) . SHIELDS, J. Exp. Med.,
1896, 1, 71 (effect of odours and mental work). STEWART (G. N.), Heart,
• 1911, 3, 33 (hands); Am. J. Phys., 1911, 28, 190 (forced breathing); Arch.
Int. Med., 1912, 9, 706 (pressures on upper arm); J. Exp. Med., 1913,
Il6o BIBLIOGRAPHY
18, 354 (feet); ib., 18, 113 (an&mias); ib., 1915, 22, 694 (collateral circu-
lation after ligation of innominate) . v. KRIES, Z. Exp. Path. Therap., 1911,
9, 453 (arteries in man).
Rate of Blood-Flow in Veins. — BURTON-OPITZ, Am. J. Phys., 1903, 7, 435:
ib., Pfliiger's Arch., 1907, 121, 150 (stromuhr) ; ib., 1908, 121, 156.
Circulation Time. — HERIXG, VIERORDT, Vierordt's Physiologie, 1871, p. 147.
LANGLOIS and DESBOUIS, J. Phys. Path. Gen., 1912, 14, 282, 1113 (pul-
monary). STEWART (G. N.), J. Phys., 1893, 15, I (electrical and methylene
blue methods).
Heart Output. — BORNSTEIN (A.), Z. Exp. Path. Ther., 1911, 9, 382 (gaso-
tnetric method in man). COWL, Arch. f. Phys., 1900, 564 (Rontgen cardio-
graphs in man). DAWSON and GORHAM, J. Exp. Med., 1908, 10, 484
(pulse pressure as index). GESELL (R.), Am. J. Phys., 1915, 38, 404.
HENDERSON (Y.) and BARRINGER, Am. J. Phys., 1913, 31, 288 (conditions
determining output). HENDERSON (Y.) and PRIXCE, ib., 1914, 35, 106
(the oxygen pulse and the systolic discharge). KNOWLTON and STARLING,
J. Phys., 1912, 44, 206 (influence of temperature and blood-pressure on
performance of isolated heart). MURLIN and GREER, Am. J. Phys., 1914,
33, 253 (relation of heart-rate to respiratory metabolism). KROGH and
LINDHARD, Skand. Arch. Phys., 1912, 27, 100 (gasometric method in man).
KROGH, ib., 27, 126, 227. PATTERSON, PIPER and STARLING, J. Phys.,
1914, 48, 465 (output depends on inflow). PLESCH, Z. Exp. Path. Ther.,
1909, 6, 380 (in man). STEWART (G. N.), J. Phys., 1898, 22, 159 (dog).
TIGERSTEDT, Skand. Arch. Phys., 1907, 19, i; ib., 1909. 22, 115 (dog).
WOLF, Arch. Int. Med., 1911, 8, 463 (cat, influence of temperature).
Pulmonary Circulation. — FUHNER and STARLING, J. Phys., 1913, 47, 286.
PLESCH, Z. f. Exp. Path. Ther., 1913. 13, 165. TIGERSTEDT, Ergeb. d.
Phys. (Bioph.), 1903, 528; Skand. Arch. Phys., 1907, 19, 231. WIGGERS,
Am. J. Phys., 1912, 30, 233. WOOD (H. C.), Am. J. Phys., 1902, 6, 283;
J. Exp. Med., 1911, 14, 326.
ORIGIN OF HEARTBEAT.
Sino-Auricular Node. — COHX, KESSEL and MASON, Heart, 1912, 3, 311, 341.
EYSTER and MEEK, Arch. Int. Med., 1916, 18, 775 (conduction of excitation
from sino-auricular node). FLACK, J. Phys., 1910, 41, 64. LEWIS and
OPPENHEIMER (B. S. and A.), 'Heart, 1910, 2, 147 (location of pacemaker).
MACLEOD, J. Lab. Clin. Med., 1916, 1, 263 (origin and spread of impulse
— resume). MEEK and EYSTER, Am. J. Phys., 1914, 84,368 (location of
pacemaker); Heart, 1914, 5, 119, 227; Am. J. Phys., 1917, 42, 611; Am.
J. Phys., 1916, 39, 291. SCHLOMOVITZ and CHASE, Am. J. Phys., 1915,
41, 112 (pacemaker in turtle's heart). MOORHOUSE, ib., 1912, 30, 358;
ib., 1913, 31, 421. OPPENHEIMER (B. S. and A.), J. Exp. Med., 1912,
16, 613 (nerves in sino-auricular node). SANSUM, Am. J. Phys., 1912, 30,
411 (extra systoles caused by stimulation of node).
Cause of Heart Beat. — CARLSON, Am. J. Phys., 1904, 12, 67, 471 (limulus).
CARLSON and MEEK, ib., 1908, 21, 1 (embryonic heart rhythm in limulns).
CYON, Pfliiger's Arch., 1906, 113, in. DALE (D.) and THACKER, J.
Phys., 1914, 47, 493 (H-ion concentration). ERLANGER, Harvey Lecture,
New York, 1912-13. GREENE (C. W.), Am. J. Phys., 1899, 2, Sz
(blood salts). HERING, Pfluger's Arch., 1907, 116, 143. KRONECKER,
Z. f. Biol., 1896, 34, 529. — LANGENDORFF, Ergeb. d. Phys., 1902, 317;
ib., 1905, 764. LAKE, J. Phys., 1916, 50, 364 (growth of heart tissue in
vitro). MARTIN (E. G.), Am. J. Phys., 1912, 30, 182 (ventricular tonus
and causation of beat); Am. J. Phys., 1913, 32, 165 (blood salts) . PORTER
(W. T.), J. Phys., 1897, 2, 391-
Extra Contraction and Compensatory Pause.- CARLSON, Am. J. Fhys., 1908,
21, 19 (limulus); ib., 1907, 18, 71 (mechanism of refractory period);
ib., 1906, 16, 67 (excitation of heart during different phases of beat). CUSHNV.
Heart, 1912, 3, 257 (stimulation of isolated ventricle). CUSHNY and
THE CIRCULATION OF THE BLOOD AND LYMPH 1161
MATTHEWS, J. Phys., 1897, 21, 213 (effects of electrical stimulation of
mammalian heart). HIRSCHFELDER and EYSTER, Am. J. Phys., 1907,
18, 222. LANGENDORFF, Ergeb. d. Phys. (Bioph.), 1902, 282 (physio-
logical properties of heart muscle). MTJLLER (FR.), Harvey Lecture, New
York, 1907 (extra systoles). SCHULTZ (W. H.), Am. J. Phys., 1908, 22,
133 (refractory period). WENKEBACH, Arch. f. Phys., 1903, 57 (compen-
satory pause) . WOODWORTH (R. S.), Am. J. Phys., 1902, 8, 213 (refractory
period and compensatory pause).
Heart Muscle Strips. — ERLANGER, Am. J. Phys., 1910, 27, 87 (auricle).
MARTIN (E. G.), ib., 1904, 11, 103 (terrapin ventricle).
CONDUCTION OF CARDIAC EXCITATION AND CONTRACTION.
Atrio - Ventricular Conduction System: Auriculo - Ventricular Bundle. —
BARKER and HIRSCHFELDER, Arch. Int. Med., 1909, 4, 193. CARLSON,
Am. J. Phys., 1908, 21, n (limulus). COHN, Heart, 1909, 1, 167 (auricula-
nodal junction). CULLIS and DIXON, J. Phys., 1911, 42, 156. ENGEL-
MANN, Pfliiger's Arch., 1894, 56, 149; 1895, 61, 275; 1890, 62, 543-
ERLANGER, Am. J. Phys., 1909, 24, 375; Arch., Int. Med., 1913, 11, 334;
ib., 1912, 30, 395 (physiology of Purkinje tissue). FR^D^RICO., Arch. Int.
de Phys., 1912, 11, 405, 478. GAULT, Am. J. Phys., 1917, 43, 22
(turtle, influence of vagus and sympathetic). HERING, Pfliiger's Arch.,
1905, 108, 267; 107, 99- HOWELL, J. Am. Med. Ass., 1906, 46, Nos. 22, 23.
KEITH, Lancet, Mar. 5, 1904. KENT, J. Phys., 1893, 14, 233; Quart. J.
Exp. Phys., 4913, 7, 193; Proc. Roy. Soc., 1914, B 87, 198. LAURENS,
Am. J. Phys., 1916-17, 42, 89, 513 (tuvile). LEWIS, WHITE and MEAKINS,
Heart, 1914, 5, 289. LEWIS, ib., 1913, 5, 21 (rate in dog's auricle). PRINCE
and CERACI, Heart, 1915, 6, 167. SALTZMAN, Skand. Arch. Phys.,
1908, 20, 233 (papillary muscles). TAWARA, "Das Reizleitungssystem
des Saugethierherzens," Jena, 1906; Zentralbl. f. Phys., 1905, 19, 70.
WHITE and KERR, Heart, 1917, 6, 207 (whale). WILSON (J. G.), Proc.
Roy. Soc., 1909, B 81, 151 (nerves of atrio-ventricular bundle).
Heart-Block. — BACHMANN, Arch. Int. Med., 1909, 4, 238 (strophanthin).
BUCHANAN (F.), J. Phys., 42, p. xix (dissociation of auricles and ventricles
in hibernation). CHRISTIAN, Arch. Int. Med., 1915, 16, 341 (digitalis).
ERLANGER, J. Exp. Med., 1905, 7, 676; ib., 1906, 8, 8. ERLANGER and
BLACKMAN, Heart, 1910, 1, 177. EYSTER and MEEK, Arch. Int. Med.,
1917, 19, 117 (sino-auricular and sino-ventricular block). EYSTER and
EVANS, ib., 1915, 16, 832. GARREY, Am. J. Phys., 1912, 30, 283 (com-
pression of cardiac nerves of limulus). GESELL, ib., 1916, 40, 267.
Fibrillation in Heart. — GARREY, Am. J. Phys., 1908, 21, 283 (influence of
cardiac nerves on); ib., 1914, 33, 397. GUNN (J. A.), Heart, 1915, 5, i
(rate). LEVY (A. G.), J. Phys., 1914, 49, 54. MAC\VILLIAM, J. Phys.,
1887, 8, 296. PORTER, Am. J. Phys., 1898, 1, 71 (recovery of heart from) .
Influence of Temperature on the Heart.— CARLSON, Am. J. Phys., 1906, 15,
207. EVANS (C. L.), J. Phys., 1917, 51, 91 (mechanism of acceleration by
warmth and adrenalin). LANGENDORFF, Ergeb. d. Phys., (Biophys.),
1903, 517. STEWART (G. N.), J. Phys., 1892, 13, 119 (heat standstill).
Isolated Mammalian Heart. — BARCROFT and DIXON, J. Phys., 1906-7, 35,
182 (gaseous metabolism). CUSHNY and GUNN, J. Pharm. Exp. Therap.,
1913, 5, i ; MANWARING, MEINHARD and DENHART, Soc. Exp. Biol. Med.,
1916, 13, 173 (effect of serum). EVANS (C. L.), J. Phys., 1914, 47, 407
(effect of glucose on gaseous metabolism). GUTHRIE and PIKE, Am. J.
Phys., 1907, 18, 14 (relation of activity to pressure in coronary). GORHAM
and MORRISON, ib., 1910, 25, 419 (action of blood proteins). LANGENDORFF,
Pfluger's Arch., 1895, 61, 291; ib., 1897, 66, 3551 *'&•. 1898, 70, 473.
LOCKE and ROSENHEIM, J. Phys., 1907, 36, 205 (consumption of dextrose).
NEUKIRCH and RONA, Pfliiger's Arch., 1912, 148, 285 (consumption of
sugars by). PORTER (W. T.), Am. J. Phys., 1898, 1, 511. WALLER and
REID, Phil. Trans. (Roy. Soc., Lond.), 1887, B 178, 215 (action of excised
heart}.
II62 BIBLIOGRAPHY
RELATION OF SALTS TO HEART ACTION.
BENEDICT (S. R.), Am. J. Phys., 1908, 22, 16; CARLSON, ib., 16, 221; EGGERS
(H. E.), ib., 1907, 18, 64 [non-electrolytes]. BOTAZZI, Arch, de Physiol.,
1896, 882 (potassium). BURRIDGE, Q. J. Exp. Phys., 1915, 8, 303 (NaCl) ;
ib., 8, 331 (Ca salts and alkalies). CLARK (A. J.), J. Phys., 1913-14, 47,
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WALLER (M. D.), J. Phys., 1914, 48, p. xlvi (electrolyte concentrations
and frequency) .
C02 and Heart. — BAYLISS, J. Phys., 1900-1, 26, p. xxxii. CATHCART and
CLARK, ib., 1913, 47, 393- JERUSALEM and STARLING, ib., 1910, 40, 279.
KETCHAM, KING and HOOKER, Am. J. Phys., 1912, 31, 64.
Resuscitation of Heart. — CRILE and DOLLEY, J. Exp. Med., 1906, 8, 713 (after
anaesthetics and asphyxia). ERLANGER, ib., 1912, 16, 452 (sinus stimu-
lation as a factor). GUNN (J. A.) and MARTIN (P. A.), J. Pharm. Exp.
Ther., 1915, 7, 31 (intraspinal medication and massage). KEMP and
GARDNER, Medical News, 83, 184 (after chloroform) . KULIABKO, Pfliiger's
Arch., 1903, 97, 539- LANGENDORFF, Ergeb. d. Phys., 1905, 769. PIKE,
GUTHRIE and STEWART, J. Exp. Med., 1908, 10, 371.
Heart Nerves (Cardio-Regulative Nerves).— CARLSON, Ergeb. d. Phys., 1909,
371 (comparative physiology of heart nerves and heart ganglia in inverte-
brates). CLARK (G. H.), Heart, 1913, 4, 379 (influence of temperature).
COHN, J. Exp. Med., 1912, 16, 732 (differences between the two vagi in dog).
CULLIS and TRIBE, J. Phys., 1913, 46, 141 (distribution of nerves in heart).
CYON, Die Nerven des Herzens (Berlin) ; Les Nerfs du Cceur, Paris, 1905.
DOGIEL and ARCHANGELSKY, Pfliiger's Arch., 1906, 113, i. ENGELMANN,
Arch. f. Phys., 1900, 315; ib., 1902, Supp. Bd., i, 103, 443 (effects of vagus
on rate, force, etc.). GARREY, Am. J. Phys., 1912, 30, 451 (effects of vagi
in heart-block); ib., 1911, 28, 33 (turtle). GASKELL, J. Phys., 1883, 4, 43
(tortoise) ; Phil. Trans. (Roy. Soc., Lond.), 1882, 993 (frog). HARRINGTON
(D. W.), Am. J. Phys., 1898, 1, 383 (guinea pig). HOUGH (T.), J. Phys.,
1895, 18, 161 (escape of heart from vagus inhibition). HUNT (R.), J. Exp.
Med., 1897, 2, 151; Am. J. Phys., 1899, 2, 395 (relation of accelerator to
inhibitory nerves). LANGENDORFF, Ergeb. d. Phys. (Bioph.), 1902, 263
(heart muscle and intracardial innervation). LEWIS (T.), Heart, 1914, 5,
247 (vagal stimulation and antrio-ventricular rhythm). MEEK and EYSTER,
Am. J. Phys., 1912, 30, 271 (electrical changes in heart during vagus
stimulation). PATON (D. N.), J. Phys., 1912, 45, 106 (birds). SCHLOMO-
VITZ, EYSTER and MEEK, Am. J. Phys., 1915, 37, 177 (relation of nodal
tissue to inhibitory nerves). SEWELL and DONALDSON (F.), J. Phys., 1880-
82, 3, 357 (influence of intracardiac pressure on vagus action). STEWART
(G. N.), J. Phys., 1892, 13, 59; Z. f. Biol., 1913, 59, 531 (influence of
temperature of heart on activity of heart nerves); Am. J. Phys., 1909, 24,
341 (tortoise vagus). WIGGERS, Am. J. Phys., 1916, 42, 133 (influence
of vagus on "fractionate " contraction of right auricle).
Accelerators. — CYON, Pfliiger's Arch., 1906, 113, m. FRED^RICO. (H.),
Arch. Internat. de Phys., 1913, 13, 115. HERING (H. E.), Pfliiger's
Arch., 1905, 107, 125 (direct action on mammalian ventricle).
Action of Accelerated on Quiescent Heart. — CARLSON, Am. J. Phys., 1904,
12, 55 (molluscs). HERING, Pfliiger's Arch., 1906, 115, 354 (mammals).
STEWART (G. N.), J. Phys., 1892, 13, 83, 90 (amphibia).
THE CIRCULATION OF THE BLOOD AND LYMPH 1163
Voluntary Acceleration of Heart. — FAVILL and WHITE, Heart, 1917, 6, 175.
VAN DE VELDE, Pfluger's Arch,, 1897, 66, 232.
Cardio-Inhibitory Centre and Reflexes. — BAINBRIDGE, J. Phys., 1914. 48,
332. EYSTER and HOOKER, Am. J. Phys., 1908, 21, 373; FILEHNE and
BIBERFIELD, Pfliiger's Arch., 1909, 128, 443 (effect of increased blood-
pressure). HOOKER, Am. J. Phys., 1908, 19, 417 (reflex acceleration
independently of cardio-inhibitory centre?). MILLER and BOWMAN, Am.
J. Phys., 1915, 39, 149. WERTHEIMER and MEYER, Arch, de Phys., 1890,
284 (influence of deglutition on heart-rhythm) .
Relation of Salts to Inhibition. — BRINE (B. M.), Am. J. Phys., 1917, 44, 171;
BURRIDGE, J. Phys., 1917, 51, 45 (Ca and K). HOGAN and ORMOND, Am.
J. Phys., 1912, 30, 105 (Ca). HOWELL, ib., 1906, 15, 280 (salts of blood).
HOWELL and DUKE, ib., 1908, 21, 51 (output of K in inhibition) ; ib., 1908,
23, 174 (accelerators and Ca, K and N metabolism of isolated heart) ; J. Phys.,
1906-7, 35, 131 (isolated mammalian heart). LANGENDORFF and HUECK,
Pfluger's Arch., 1903, 96, 473 (Ca). LOEB (J.), J. Biol. Ch., 1906, 1,
427 (Mg and Ca on contractions of jellyfish). MARTIN (E. G.), Am. J.
Phys., 1904, 11, 370 (KCl).
VASOMOTOR NERVES.
BOWDITCH and WARREN, J. Phys., 7, 4l6 (of limbs). DRINKER (C. K. and
K. R.), Am. J. Phys., 1916, 40, 514 (of bone-marrow) . GASKELL (W. H.),
J. Phys., 1878-9, 1, 262 (vasomotors of muscles). LANGLEY, J. Phys.,
1891, 12, 345, 375 (course of sweat and vasomotor fibres of cat's foot) ; ib.,
1911, 41, 483 (frog's foot).
Vasomotors of Intestine. — BUNCH (J. L.), J. Phys., 1899, 24, 72. BURTON-
OPITZ, Am. J. Phys., 1915, 35, 203 (duodenum). HALLION and FRANCOIS-
FRANCK, J. Phys. Path. Gen., 1896, 478, 493.
Vasomotors of Lungs. — BRODIE and DIXON, J. Phys., 1904, 30, 476.
FRANCOIS-FRANCK, Arch, de Phys., 1896, 178. JACKSON, J. Pharm. Exp.
Ther., 1913, 4, 291. KROGH, Zentralbl. f. Physiol., 20, 802 (tortoise).
LANGLOIS and DESBOUIS, J. Phys. Path. Gen., 1912, 14,282. PLUMIER,
ib., 1904, 655. TIGERSTEDT, Ergeb. d. Phys. (Bioph.), 1903. 571.
TRIBE (E. M.), J. Phys., 1914, 48, 154. WIGGERS, J. Pharm. Exp. Ther.,
1909, 1, 341-
Cerebral Vasomotors. — BAYLISS and HILL, J. Phys., 1895, 18, 334. DIXON
and HALLIBURTON, Q. J. Exp. Phys., 1910, 3, 315. GULLAND (G. L.),
J. Phys., 1895, 18, 361; HUBER (G. C.), J. Comp. Neurol., 1899, 9, i;
HUNTER (W.), J. Phys., 1900-1, 26, 465 (histological). HILL and MACLEOD,
ib., 26, 394- JENSEN, Pfliiger's Arch., 1904, 103, 171, 196. WIGGERS,
Am. J. Phys., 1905, 14, 452; ib., 1907, 20, 206; ib., 1908, 21, 454; J. Phys.,
1914, 48, 109.
Vasomotors of Heart. — BRODIE and CULLIS, J. Phys., 1911, 43, 313. DOGIEL
and ARCHANGELSKY, Pfliiger's Arch., 1907, 116, 482. PORTER, Am.
J. Phys., 1912, 29, p. xxxi (method). WIGGERS, ib., 1909, 24, 391.
Vasomptors of Veins (Veno-Motors) . — BANCROFT, Am. J. Phys., 1898, 1, 477
(hind limb). BAYLISS and STARLING, J. Phys., 1894, 17, 120; BURTON-
OPITZ, Q. J. Exp. Phys., 1913, 7, 57 '> An*. J- Phys., 1914, 36, 325;
EDMUNDS (C. W.), J. Pharm. Exp. Ther., 1915, 6, 569 (portal vein).
FRANCOIS-FRANCK and HALLION, Arch, de Phys., 1897, 434 (liver).
HENDERSON (Y.), Am. J. Phys., 1917, 42, 589 (veno-pressor mechanism).
Vasomotor Mechanism. — ASHER, Ergeb. d. Phys. (Biophys.), 1902, 346.
BAYLISS, ib., 1906, 319. COTTON, SLADE and LEWIS, Heart, 1917, 6, 227
(contractile power of capillaries). EDWARDS (D. J.), Am. J. Phys., 1916,
35, 15 (compensatory phenomena during splanchnic stimulation). HOOKER,
Am. J. Phys., 1911, 28, 361 (chemical regulation of vascular tone). PORTER
and NEWBURGH, ib., 1914, 3«f, i (in pneumonia). PORTER and TURNER,
ib., 1915, 39, 236 (vasotonic and vasore flex mechanism).
H64 BIBLIOGRAPHY
Vasomotor Centres. — MATHISON, J. Phys., 1911, 42, 283; PORTER (\\. T.),
Am. J. Phys., 1913, 31, p. xxix (functional relation of nerve cells in); ib.,
1915, 36, 418 (vasotonic and vasoreflex centre). PORTER and CLARK, ib.,
1908, 21, p xv (difference between bulbar and spinal vasomotor cells).
PORTER and STOREY, ib., 1907, 18, 181 (effect of injuries of brain).
RANSON, ib., 1916, 42, i (chief vasoconstrictor centre). SOLLMANN and
PILCHER, ib., 1910, 26, 233 (effect of sciatic stimulation and curara).
Vasodilators. — BAYLISS, J. Phys., 1900, 26, 173; ib., 1902, 28, 276 (hind limb,
antidromic impulses'). BERNARD (CL.), Liquides de 1'organisme, 2, 269
(chorda). CARLSON (A. J.), Am. J. Phys., 1907, 19, 408; MCLEAN (F. C.),
ib., 22, 279 (vasodilators to siibmaxillary in, cat's cervical sympathetic).
ECKHARD, Beitrage, 3, 125; 4, 69 (mervi erigentes). KENDALL and
LUCHSINGER, Pfliiger's Arch., 1876, 13, 197 (difference between dilators
and constrictors after nerve section) .
Depressor. — BAYLISS, J. Phys., 1908, 37, 264. CYON, Pflitger's Arch., 1901,
84, 304. PORTER and BEYER, Am. J. Phys., 1900, 4, 283. RANSON
and BILUNGSLEY, Am. J. Phys., 1916, 42, 9. SEWALL and STEINER,
J. Phys., 1885, 6, 162. SOLLMANN and PILCHER, Am. J. Phys., 1912,
30, 369 (response of vasomotor centre to). TIGERSTEDT, Skand. Arch.
Phys., 1908, 20, 330. TSCIIIRWINSKY, Zentralb. f. Phys., 9, 777; 10,65.
Vasomotor Reflexes. — HENDERSON (V. E.) and LOEWI (O.), Arch. Exp. Path.
Pharm., 1905, 53, 56 (vasodilator excitation). HUNT, J. Phys., 1895, 18,
381 (fall of blood-pressure on stimulation of afferent nerves). LANGLEY,
J. Phys., 1912, 45, 239 (effect of strychnine). MARTIN and LACEY, Am.
J. Phys., 1914, 33, 212 (vasomotor reflex thresholds). MARTIN and
MENDENHALL,^., 1915, 38, 98 (vasodilator response to sensory stimulation) .
MARTIN and STILES, ib., 1916, 40, 194 (vasomotor summations) . PORTER,
ib., 1907, 20, 399 (uniform stimuli with blood-pressure at different levels);
ib., 1910, 27, 276 (relations of afferent impulses to vasomotor centres').
PORTER and MARKS, ib., 1908, 21, 460 (effect of hemorrhage). PORTER
and RICHARDSON, ib., 1908, 23, 131. STEWART (G. N.), Heart, 1911, 3,
76; STEWART and LAFFER, Arch. Int. Med., 1913, 11, 365; STEWART and
WALKER, ib., 11, 383 (elicited by warmth and cold in man). VINCENT and
CAMERON, Q. J. Exp. Phys., 1915, 9, 45.
Influence of Asphyxia on Circulation. — HILL and FLACK, J. Phys., 1908, 37,
77 (on circulation and respiration). MACWILLIAM, J. Phys., 1901-2, 27,
337 (asphyxia and cardiac failure) . MATHISON, ib., igii, 42, 283 (medul-
lary centres) ; ib., 1910, 41, 416. SOLLMANN and PILCHER, Am. J. Phys.,
1911, 29, 100 (reaction of vasomotor centre to asphyxia).
Pressor Amines. — ABELOUS andBARDiER, Compt. Rend. Soc. deBioL.Mar.ij,
1906; DALE and DIXON, J. Phys., 1909, 39, 25 (formed in putrefaction).
BAEHR and PICK, Arch. Exp. Path. Pharm., 1916, 80, 161 (point of attack).
BAIN (W.), Q. J. Exp. Phys., 1914, 8, 229 (pressor bases in urine). DALE
and LAIDLAW, J. Phys., 1911, 43, 182; LAIDLAW, Bioch. J., 1911, 6, 141
(action). WALPOLE, J. Phys., 1909, 38, 243.
Depressor Amine (" Vasodilation ") . — BARGER and DALE, J. Phys., 1911,
41, 499; MELLANBY and TWORT, ib., 1912, 45, 53 (in intestine wall).
Intracranial Pressure. — GUSHING (H.), Johns Hopkins Hosp. Bull., Sep., 1901.
EYSTER, BURROWS and ESSICK, J. Exp. Med., 1909, 11, 489.
Influence of Gravity on Circulation. — HILL (L.), J. Phys., 1895, 18, 15. HILL
and BARNARD, ib., 1897, 21, 323. SALATH:!:, Compt. Rend., 1877, 85, 445.
SHOCK.
BAINBRIDGE and BULLEN, Lancet (London), 1917, 2, 51. BAYLISS (W. M.),
Arch. Med. Beiges, 1917, 70, 793 (Physiol. Abstracts, 1918, 2, 625) (treat-
ment by intravenous injections). ERLANGER and WOODYATT, J. Am. Med.
Ass., 1917, 69, 1410; ERLAXGER, GESELL, GASSER and ELLIOTT, ib., 1917,
69, 2089. GUTHRIE, ib., 1917, 69, 1394. HENDERSON (Y.), Am. J. Phys.,
v RESPIRATION 1165
1908, 21, 126; ib., 1909, 23, 345; ib., 1310, 27, 152; HENDERSON and
SCARBROUGH, ib., igio, 26, 260 (acapnia and shock). HENDERSON,
ib., 1910, 25, 310, 385; HENDERSON, PRINCE and HAGGARD, J. Am. Med.
Ass., 1917, 69, 965. JANEWAY and JACKSON, Soc. Exp. Biol. Med., 1915,
12, 193; J. Am., Med. Ass., Oct. 16, 1915, 371. LYON and SWARTZ, Soc.
Exp. Biol. Med., 1910, 7, 139. MELTZER, Arch. Int. Med., 1908, 1, 571,
MORRISON and HOOKER, Am. J. Phys., 1915, 37, 86. PIKE and COOMBS,
J. Am. Med. Ass., 1917, 68, 1892. PORTER, Bost. Med. Surg. J., 1917,
177, 326. PORTER, MARKS and SWIFT, Am. J. Phys., 1907, 20, 444.
PORTER and QUINBY, Am. J. Phys., 1908, 20, 500. SEELIG and JOSEPH,
J.Lab. Clin. Med., 1916,1,283. SIMONDS, J. Am. Med. Ass., 1917,69,883.
Transfusion. — BOTAZZI and JAPELLI, Bioch. Z., 1908, 11, 331 (physico-chemical
properties of blood and lymph after). CARLSON and GINSBURG, Am. J.
Phys., 1915, 36, 280 (influence on hyperglyc&mia of pancreatic diabetes).
CRILE (G. W.), Soc. Exp. Biol. Med., 1906, 4, 6. HASKINS (H. D.), J.
Biol. Ch., 1907, 3, 321 (effect on N metabolism). OTTENBERG and
THALHIMER, J. Med. Res., 1915, 33, 213. RABENS, Am. J. Phys., 1914,
36, 294 (influence on kidneys).
Lymph Hearts. — ABEL and TUNNER, J. Pharm. Exp. Ther., 1914, 6, 91
(action after cardieciomy) . LANGENDORFF, Pfliiger's Arch., 1906, 115,
533. MOORE (A.), Am. J. Phys., 1901, 5, 87 (influence of ions); ib., 5,
196 (spinal centres). PRIESTLEY (J.), J. Phys., 1878-9, 1, i, 19 (older
literature). TSCHERMAK, Pfliiger's Arch., 1907, 119, 165 (spinal in-
nervation) .
Channels in Liver Cells communicating with Blood Capillaries. — SCHAFER,
Anat. Anzeig., 1902, 21, 18. HERRING and SIMPSON, Proc. Roy. Soc.,
1906, B 78, 455-
CHAPTER IV.
RESPIRATION.
Blood in Lungs. — KUNO, J. Phys., 1917, 51, 154.
Respiratory Movements. — BAGLIONI, Ergeb. d. Phys., 1911, 526. EYSTER,
AUSTRIAN and KINGSLEY, Am. J. Phys., 1907, 18, 413 (temporary occlusion
of aorta). FITZ (G. W.), J. Exp. Med., 1896, 1, 677. DU BOIS-REYMOND
(R.), Ergeb. d. Phys. (Bioph.), 1902, 377 (mechanics of respiration).
GUTHRIE and PIKE, Am. J. Phys., 1906, 16, 475; 1907, 20, 45 (effect oj
change in blood-pressure on). LUNDSGAARD and VAN SLYKE, J. Exp. Med.,
1918, 27, 65 (lung volume).
Temperature of Expired Air. — LOEWY and GERHARTZ, Pfliiger's Arch., 1914,
155, 231.
Artificial Respiration and Resuscitation. — SCHAFER, Lancet, May 30, 1903;
Trans. Roy. Med.-Chir. Soc., London, 1904, 86; Proc. Roy. Soc. (Edin.),
1904, 25, 39 (in the apparently drowned). STEWART (G. N.) and PIKE
(F. H.), Am. J. Phys., 1907, 19, 328 (resuscitation of respiratory and other
bulbar centres, with reference to their automatism).
Respiratory Dead Space. — DOUGLAS and HALDANE, J. Phys., 1912, 45, 235.
HALDANE (J. S.), Am. J. Phys., 1915, 38, 20. HENDERSON (Y.) ET AL.,
Am. J. Phys., 1915, 38, i. KROGH (A.) and LINDHARD (J.), J. Phys.,
1917, 51, 59; ib., 1913, 47, 30. PEARCE (R. G.) and HOOVER (D. H.),
Am. J. Phys., 1917, 44, 391.
Alveolar Air. — HOUGH (T.), Am. J.Phys., 1912, 30, 18 (alveolar air in muscular
exercise). HALDANE and PRIESTLEY, J. Phys., 1905, 32, 225. HENDERSON
(Y.) and MORRISS (W. H.), J. Biol. Ch., 1917, 31, 217. KROGH and
LINDHARD, J. Phys., 1914, 47, 431. MACLEOD (J. J. R.), J. Lab. Clin.
Med., 1916, 1, 522 (clinical method for determination of CO% in alveolar air).
PEARCE (R. G.), Am. J. Phys., 1917, 44, 369. VAN SLYKE, STILLMAN
and CULLEN, J. Biol. Ch., 1917, 30, 401 (alveolar COZ and plasma bicar-
bonate).
Ii66 BIBLIOGRAPHY
Respiratory Gaseous Exchange. — -BENEDICT and ROMANS, Am. J. Phys.,
1911, 28, 29. BENEDICT (F. G.). ib., 1909, 24, 345 (apparatus). BENE-
DICT and TOMPKINS, Boston Med. Surg. J., 1916, 174, 857, 898, 939
(apparatus for clinical use) . CARPENTER, Carnegie Instit. Pub., No. 216,
1915 (methods in man). JAQUET, Ergeb. d. Phys. (Bioch.), 1902, 457.
PEMBREY, J. Phys., 1901, 27, 66 (marmot). WOLF and HELE, J. Phys.,
1914, 48, 428 (decerebrate animal).
Respiratory Quotient. — BENEDICT, EMMES and RICHE, Am. J. Phys. 1911,
27, 383 (influence of preceding diet on). LUSK, Arch. Int. Med., 1915, 15,
939 (diabetes).
BLOOD GASES.
BARCROFT, J. Phys:, 1908, 37, 12; BARCROFT and HIGGINS, ib., 1911, 42,
512; BARCROFT and ROBERTS, ib., 1910, 39, 429 (differential method).
BUCKMASTER, J. Phys., 1917, 51, 164 (relations of COZ in blood). BUCK-
MASTER and GARDNER, J. Phys., 1910, 40, 373 (gas pumps); ib., 1910,
41, 60 (gases of arterial and venous blood); ib., 1912, 43, 401 (nitrogen).
COOKE and BARCROFT, J. Phys., 1914, 47, p. xxxv (percentage saturation
of O2 in arterial blood in man). FRIEDMAN (E. D.) and JACKSON (H. C.),
Arch. Int. Med., 1917, 19, 767 (CO2 of blood and alveolar air in obstructed
respiration). HALDANE, J. Phys., 1898, 22, 465 (analysis). KROGH,
Skand. Arch. Phys., 1908, 20, 259 (microtonometer) . MURLIN, EDELMANN
and KRAMER, J. Biol. Ch., 1913, 16, 79 (after clamping abdominal aorta
and inferior cava). PETERS (J. P.), Am. J. Phys., 1917, 43, 113 (C02
acidosis and cardiac dyspnoea). RASMUSSEN, Am. J. Phys., 1915, 39,
20; ib., 1916, 41, 162 (blood gases in hibernation).
Oxygen Tension of Arterial Blood. — HALDANE and SMITH, (J. L.), J. Phys.,
1896, 20, 497. KROGH, Skand. Arch. Phys., 1910, 23, 252. OSBORNE
(W. A.), J. Phys., 1907, 36, 48. SCOTT (R. W.), Am. J. Phys., 1917, 44,
196 (decerebrate cat).
C02 Tension. — BOOTHBY and SANDFORD, Am. J. Phys., 1916, 40, 547 (venous
blood, rest and work). CHRISTIANSEN, DOUGLAS and HALDANE, J. Phys.,
1914, 48, 244. HENDERSON (Y.) and PRINCE, J. Biol. Ch., 1917, 32, 325
(venous blood).
Oxygen Dissociation Curves (of Blood and Oxyheemoglobin) . — BARCROFT and
CAMIS, J. Phys., 1909, 39, 143. BARCROFT and ORBELI, ib., 1910, 41,
355 (influence of lactic acid). BARCROFT, ib., 1911, 42, 44 (altitude).
BARCROFT and KING, ib., 1907, 39, 374 (temperature). BOHR, HASSEL-
BALCH and KROGH, Skand. Arch. Phys., 1906, 16, 402 (influence of C02).
DOUGLAS and HALDANE (J. S. and J. B. S.), J. Phys.. 1912, 44, 275
(combination of Hb with COZ and O2). HUFNER, Arch. f. Phys., 1901,
Supp. Bd., 187 (dissociation of oxyh&moglobin). MATHISON, J. Phys.,
1911, 43, 347 (influence of acids on reduction of arterial blood).
Oxygen Capacity of Blood. — BARCROFT and BURN, J. Phys., 1913, 45, 493-
BURN, ib., 1913, 45, 482. DOUGLAS, ib., 1910, 39, 453 (after hemorrhage) ;
ib., 1910, 40, 472 (total Oz capacity and blood volume at different altitudes).
HALDANE, ib., 25, 295 (ferricyanide method). HUFNER, Arch. f. Phys.,
1894, 130; ib., 1903, 217 (Oz-capacity of blood pigment). PETERS, J. Phys.,
1912, 44, 131.
Carbon Monoxide. — GRJSHANT, Arch, de Phys., 1898, 315, 434 (absorption).
HALDANE, J. Phys., 18, 201, 430 (action). NASMITH and GRAHAM, ib.,
35, 32 (poisoning). NICLOUX, J. Phys. Path. Gen., 1914, 6, 145, 164
(absorption) .
Chemical Regulation of Respiration. — BAYLISS and STARLING, Ergeb. d.
Phys., 1906, 669. CAMPBELL, DOUGLAS, HALDANE and HOBSON, J.
Phys., 1913, 46, 301. GASSER and LOEVENHART, J. Pharm. Exp. Ther.,
1914, 5, 239 (decreased 02). GORDON and HALDANE, J. Phys., 1909,
38, 420. HALDANE and POULTON, ib., 1908, 37, 390 (Qy deficiency).
HALDANE and PRIESTLEY, ib., 1905, 32, 225. HOUGH, Am. J. Phys.,
RESPIRATION 1167
, 28, 369 (breathing a confined volume of air). HILL and FLACK,
J. Phys., 1908, 37, 77 (excess of CO2 and want of O2). PETERS, Am. J.
Phys., 1917, 44, 84 (H-ion concentration of blood). SCOTT (R. W.), Am.
J. Phys., 1917, 44, 196 (COZ and H-ion concentration in decerebrate cat).
Nervous Mechanism of Respiration. — BARRY, J. Phys., 1913, 45, 473 (afferent
impressions). BORUTTAU, Ergeb. d. Phys. (Biophys.), 1902, 403.
DEASON and ROBB, Am. J. Phys., 1911, 28, 57 (paths in cord). GAD,
Arch. f. Phys., 1880, i. GRUBER, Am. J. Phys., 1917, 42, 450. NICE,
Am. J. Phys., 1914, 33, 204 (thresholds for respiratory reflex). FROHLICH, .
Pfliiger's Arch., 1906, 113, 433 (elimination of vagus without stimulation).
HALDANE and MAVROGORDATO, J. Phys., 1916, 50, p. xli (vagus regulation).
LOEWY (A.), Pfliiger's Arch., 1888, 42, 273. LEWANDOWSKY, Arch. f.
Phys., 1896, 195. MELTZER, Arch. f. Phys., 1892, 340. NICOLAIDES,
Arch. f. Phys., 1907, 68. PORTER (W. T.), J. Phys., 1894-5, 17, 455
(phrenic path). PORTER and TURNER, Am. J. Phys., 1913, 32, 95 (reflex
respiratory movements). STEWART (G. N.), ib., 1907, 20, 407. STEWART
and PIKE, ib., 1907, 19, 328; ib., 20, 61 (resuscitation of nervous respira-
tory mechanism).
Respiratory Centre. — BAGLIONI, Ergeb. d. Phys., 1911, 588 (automatism of).
BORUTTAU, ib., 1904, 89. BROWN (T. G.), J. Phys., 1914, 48, p. xxxii
(a respiratory tract in mid-brain). HOOKER, J. Pharm. Exp. Ther., 1913,
4, 443 (perfusion in frog). LAQUEUR and VERZA"R, Pfliiger's Arch., 1912,
143, 395 (specific action of C0zon). LOEWY, ib., 1888, 42, 245 (repetition
of MARCKWALD'S experiments on paraffin injection [Z. f. Biol., 1890, 26,
259]).
Bronchi. — ABBOTT, J. Med. Res., 1912, 26, 513. DIXON and BRODIE, J. Phys.,
1903, 29, 97; DIXON and RANSOM, J. Phys., 1912, 45, 413 (innervation) .
DU BOIS-REYMOND (R.), Ergeb. d. Phys. (Bioph.), 1902, 396 (alterations
in calibre). HENDERSON (V, F..) and TAYLOR, J. Pharm. Exp. Ther.,
1910, 2, 153 (secretion). JACKSON, ib., 1914, 5, 479 (drugs).
Dyspnoea. — ATHANASIU and CARVALLO, Arch. d. Phys., 1898, 95 (heat dyspnoea).
LEWIS, RYFFEL, WOLF, COTTON and BARCROFT, Heart, 1915, 5, 45
(dyspnoea in cardiac and renal patients). MOORHOUSE, Am. J. Phys.,
1911, 28, 223 (heat dyspnoea).
Apncea. — BOOTHBY, J. Phys., 1912, 45, 328. Fol, Arch. di. Fis., 1911, 9,
453. GITHENS and MELTZER, Soc. Exp. Biol. Med., 1914, 12, 64.
MILROY, Q. J. Exp. Phys., 1913, 6, 373. Mosso, Arch. Ital. de Biol.,
40, i. PEMBREY and PITTS, J. Phys., 1899, 24, 305 (respiration in
hibernation). SCARBROUGH and HENDERSON, Am. j. Phys., 1910, 25,
p. xiii.
Cheyne-Stokes Respiration. — BARBOUR, J. Pharm. Exp. Ther., 1914, 5, 393
(morphine). CLARK (A. J.) and HAMILL, ib., 357 (circulatory changes in).
DOUGLAS, J. Phys., 1910, 40, 454 (at high altitudes). EYSTER, J. Exp.
Med., 1906, 8, 565. FULTON, Heart, 1915, 6, 77. GORDON and HALDANE,
J. Phys., 1909, 38, 401. MACKENZIE and CUSHNY, ib., 1907, 36, p. xiii.
PEMBREY, BEDDARD and FRENCH, ib., 1906, 34, p. vi. PEMBREY and
ALLEN, J. Phys., 1905, 32, p. xviii. POLLOCK, Arch. Int. Med., .1912,
9, 406.
Mechanism of Gas Exchange in Lungs.— BOOTHBY and BERRY, Am. J. Phys.,
1915, 37, 433; CHRISTIANSEN and HALDANE, J. Phys., 1914, 48, 273
(influence of distension of lungs). DIXON and RANSOM, J. Pharm. Exp.
Ther., 1914, 5, 539 (effect of altered vascular conditions in lungs) . DOUGLAS
and HALDANE, J. Phys., 1912, 44, 305 (causes of O2 absorption in lungs).
EVANS and STARLING, J. Phys., 1913, 46, 413 (oxidation in lungs).
HALDANE and LORRAIN SMITH, ib., 1898, 22, 231, 307. HARTRIDGE,
ib., X9i2, 45, 170 (O^secretion ?). KROGH (M.), ib., 1915, 49, 271 (diffusion
through lungs).
Swim Bladder. — BAGLIONI, Z. allg. Phys., igro, 11, 145. JAEGER, Pfluger's
Arch., 1903, 94, 65.
1 1 68 BIBLIOGRAPHY
•
Tissue Respiration. — BATTELLI and STERN, J. Phys. Path. Gen., 1907, 9, I,
34. BURROWS, Am. J. Phys., 1917, 43, 13 (O.z-pressure necessary for
tissue activity) . FLETCHER, J. Phys., 1898, 22, 10; 1902, 28, 54 (survival
respiration of muscle). JACKSON (D. E.), J. Lab. Clin. Med., 1916, 2,
145 (action of drugs on rate of O ^-consumption) . MANN and GAGE, J.
Phys., 1912, 45, p. ix (nuclei and metabolism, particularly in blood).
NEWMAN, Am. J. Phys., 1906, 15, 371 (limulus heart). VERNON, J. Phys.,
I9°9. 39, 149 (action of poisons); ib., 1907, 36, 81 (perfusion experiments);
ib., 1910, 40, 295 (tortoise heart). HARRIS (D. F.), J. Bio). Ch., 1915,
23, 469 (time required for reduction of oxyhcemoglobin in vivo). LESSER,
Ergcb. d. Phys., 1909, 742 (life without oxygen). PACKARD, Am. J. Phys.,
1907, 18, 164, ib., 1908, 21, 210 (resistance to lack of oxygen).
Reducing Power of Tissues. — HARRIS and IRVINE, Bio,ch. J., 1906, 1, 355.
HERTER, Am. J. Phys., 1904, 12, 128, 457.
Gaseous Metabolism of Organs. — BARCROFT and BRODIE, J. Phys., 1905, 32,
18; ib., 33, 52 (kidney). BARCROFT and DIXON, ib., 1906-7, 35, 182 (heart).
BARCROFT and SHORE, ib., 1912, 45, 296 (liver). BARCROFT and STARLING,
ib., 1904, 31, 496 (pancreas). BARCROFT and MULLER, ib., 1912, 44, 259
(submaxillary gland). BOYCOTT, ib., 1905, 32, 343 (intestine). EVANS,
ib., 1912, 45, 213 (heart and lungs). HILL and NABARRO, ib., 1895, 18,
218 (brain and muscle). LANGLEY and ITAGAKI, ib., 1917, 51, 202
(oxygen use of denervated muscle). NEUMAN, ib., 1912, 45, 188 (supra-
renal). PEARCE and CARTER, Am. J. Phys., 1915, 38, 350 (influence of
vagus on gaseous metabolism of kidney). VERZA"R, J. Phys., 1912, 44,
243; Ergeb. d. Phys., 1916, i (muscle).
Experiments Bearing on Mechanism of Oxidations in the Body. — BUNZEL,
J. Biol. Ch., 1909, 7, 157 (mechanism of oxidation of glucose by bromine).
CUSHNY, Arch. Exp. Path. Ther., Supp. Bd., 1908, 126 (action of oxidizing
salts). DAKIN, J. Biol. Ch., 1907, 3, 57 (simple aliphatic substances).
GUTHRIE (F. V.), Sac. Exp. Biol. Med., 1910, 7, 152 (modification of
tissue oxidation in vitro). HARDEN and MACLEAN, J. Phys., 1911, 43, 34
(oxidation of isolated tissues). MATHEWS and McGuiGAN, Am. J. Phys.,
1907, 19, 199 (oxidizing power of cupric acetate solutions). MCCLENDON,
J. Biol. Ch., 1915, 21, 275 (oxidizing power of oxyh&moglobin and
erythrocytes) . UNDERBILL and CLOSSON, Am. J. Phys., 1905, 13, 358
(met hylene blue, etc.). Usui, Pfliiger's Arch., 1912, 147, 100 (measure-
ment of tissue oxidations in vitro).
Oxidizing Ferments. — ABELOUS and BIARNES, Arch, de Phys., 1896, 311;
ib., 1898, 664; ib., 1897, 277. BATTELLI and STERN, Ergeb. d. Phys.,
191°. 10, 531; ib., 1912, 12, 96, 197. BERTRAND, Arch, de Phys., 1896,
23 (laccase). BUNZEL, J. Biol. Ch., 1916, 24, 91 (mode of action) ;ib., 1916,
28, 315 (relation to H-ion concentration); ib., 24, 103 (plants). KASTLE,
Hyg. Lab. Bull., No. 59, Dec., 1909. KASTLE and PORCH, J. Biol. Ch.,
1908, 4, 301 (peroxidase reaction of milk). LILLIE, J. Biol. Ch., 1913, 15,
237 (formation of indophenol at nuclear and plasma membranes of frogs'
blood-corpuscles). LOEVENHART and GROVE, J. Pharm. Exp. Ther., 1911,
3, 101. MOORE and WHITLEY, Bioch. J., 1909, 4, 136. REED, J. Biol.
Ch., 1915, 22, 99 (role in respiration); ib., 1916, 27, 299 (relation to H-ion
concentration).
Catalases. — AMBERG and WINTERNITZ, J. Biol. Ch., 1911, 10, 295 (sea-urchin
eggs). ARKIN, Am. J. Phys., 1917, 42, 603. BATTELLI and STERN, Ergeb.
d. Physiol., 1910, 531. BURGE, Am. J. Phys., 1917, 43, 545; 44, 75, 290;
ib., 1916, 41, 153 (muscles). BURGE, KENNEDY and NEILL, Am. J.
Phys., 1917, 43, 433 (effect of thyroid feeding). EVANS. Bioch. J., 1907,
2, 133 (blood). LOEW, Pfluger's Arch., 1909, 128, 560; IT. S. Dept. Agric.
Rep., No. 68, 1901. MENDEL and LEAVENWORTH, Am. J. Phys., 1908,
21 85 (tissues). SHAFFER, Am. J. Phys., 1905, 14, 299. WINTERNITZ
and MELOY, J. Exp. Med., 1908, 10, 759 (blood). WINTERNITZ and
PRATT, J. Exp. Med., 1910, 12, i, 115 (blood). WINTERNITZ and. ROGERS,
ib., 1910, 12, 12, 755 (eggs).
RESPIRATION- 1169
Reductases. — HARRIS (D. F.), J. Biol. Ch., 1915, 22, 535. HARRIS and
CREIGHTON, ib., 21, 303 ; 20, 179; Bioch. J., 1914, 8, 585.
Bioluminescence (Phosphorescence). — HARVEY, Am. J. Phys., 1915, 37, 230;
ib., 1916, 41,449, 454; ib., 1917, 42, 318; J. Biol. Ch., 1917, 31, 311.
KASTLE and MCDERMOTT, Am. J. Phys., 1910, 27, 122. MOORE, Bioch.
J., 1908, 4, i.
COMPRESSED AND RAREFIED AIR.
Caisson Illness. — BOYCOTT and DAMANT, J. Phys., 1907-8, 36, p. xiv. HAM
and HILL, ib., 1905-6, 33, pp. v, vi, vii. HILL and MACLEOD, ib., 1903,
29, 382, 492. HILL and GREENWOOD, Proc. Roy. Soc., 1906, B 77, 442;
1907, B 79, 21, 284; 1908, B 80, 12. TWORT and HILL, J. Phys., 1910,
41, p. v.
Effects of Atmospheres Rich in Oxygen. — BENEDICT and HIGGINS, Am. J.
Phys., 1911, 28, i (effect of Oz-rich mixtures on man). BULLOTT, J. Phys.,
1904, 31, 359 (action of O2 at low and high pressure on the cornea). HILL
and MACLEOD, Proc. Roy. Soc., B 70, 455, 465 (effects of an atmosphere of
O% on respiratory exchange and circulation in mouse and frog) . HILL and
FLACK, J. Phys., 1910, 40, 347 (effect of oxygen inhalation on muscular
work). KARSNER, J. Exp. Med., 1916, 23, 149. KARSNER and ASH,
J. Lab. Clin. Med., 1917, 2, 254. LORRAIN SMITH, J. Phys., 1899, 24, 19
(pathological effect of increased O2 tension). Mosso, Arch, de Phys. et
Path., 1878, 10, 76 (action of compressed air).
Influence of High Altitudes. — BARCROFT, J. Phys., 1911, 42, 44; ib., 1913,
46, p. xxx. BARTLETT, Am. J. Phys.r 1904, 10, 149. BOYCOTT and
HALDANE, J. Phys., 1908, 37, 355 (low atmospheric pressures) . COHNHEIM,
Ergeb. d. Phys. (Bioch.), 1903, 612. DOUGLAS, HALDANE, HENDERSON
and SCHNEIDER, Proc. Roy. Soc. (Lond.), 1913, B 85. DURIG and
ZUNTZ, Arch. f. Phys., 1904, Supp. Bd., 417. HUEPPE, Pfluger's Arch.,
1903, 95, 447. Mosso and MARRO, Arch. Ital. Biol., 1903, 39, 387.
SCHNEIDER ET AL., Am. J. Phys., 1908, 23, 90; ib., 1914, 34, 29; ib., 1916,
40, 380 (circulation). TISSOT, J. de Phys. Path. Gen., 1910, 12,520; ib.,
1911, 13, 75 (mountain sickness). WARD, J. Phys., 1908, 37, 378. ZUNTZ
and v. SCHROTTER, Arch. f. Phys., 1902, Supp. Bd., 430, 436 (balloon).
Influence of Respiration on Circulation. — GOLLA and SYMES, J. Phys., 1916,
50, p. xxxii (cerebrospinal pressure and respiratory movements). HENDER-
SON and BARRINGER, Am. J. Phys., 1913, 31, 399 (respiration and heart
output). SNYDER, Am. J. Phys., 1915, 27, 104 (causes of respiratory
change in heart rate] .
RespTatory Waves in Blood-Pressure. — ERLANGER and FESTERLING, J. Exp.
Med., 1912, 15, 370. LEWIS (T.), J. Phys., 1908, 37, 213, 233. SNYDER,
Am. J. Phys., 1915, 36, 430. WIGGERS, Am. J. Phys., 1911, 35, 124 (in
pulmonary artery).
Cutaneous Respiration. — BARRATT, J. Phys., 1897, 21, 192 (COZ and H2O);
ib., 24, ii (varnished skin). BOHR, Skand. Arch. Phys., 1900, 10, 74
(frog). REID and HAMBLEY, J. Phys., 1895, 18, 411 (C02infrog).
CHAPTER V.
VOICE AND SPEECH.
FLEEMING JENKIN and EWING, Trans. Roy. Soc. (Edin.), 1879, 28, 745 (vowe
sounds). GRUTZNER, Ergeb. d. Physiol. (Bioph.), 1902, 466 (voice and
speech). HERMANN, Pflugcr's Arch., 1901, 83, i, 33 (consonants) ; ib., 86,
92 (vowel sounds). MCKENDRICK, Trans. Roy. Soc. (Edin.), 37, Pt. 4.
MEYER, The Organs of Speech. PAULSEN, Pfluger's Arch., 1895, 61,
407 (the singing voice of children)', ib., 1899, 74, 570 (pitch of the voice).
RUSSELL (J. S. R.), Proc. Roy. Soc., 1892, 102 (innervation tff •glottis).
SCRIPTURE, Study of Speech Curves, Carnegie Instit. Pub., Washington,
1906.
74
CHAPTER VI.
DIGESTION.
MOVEMENTS OF ALIMENTARY CANAL.
CANNON, Mechanical Factors of Digestion, New York, 1911; J.A.M.A., 1903,
40, 749-
Deglutition. — BOTAZZI, J. Phys., 1899, 25, 157 (nerves}. CANNON, Am. J.
Phys., 1907, 19, 436 (cesophageal peristalsis after vagotomy). CANNON
and MOSER, ib., 1898, 1, 435. KAHN, Arch. f. Phys., 1903, Supp. Band.,
386 (nerves); ib., 1906, 355, 362. KAISER, Arch. Neerland de. Ph3's.,
1917, 1, 148. MELTZER, J. Exp. Med., 1897, 2, 453; Soc. Exp. Biol. Med.,
1906, 3, 52 (reflexes); Brit. Med. J., Dec. 22, 1906 (vagus reflexes); Soc.
Exp. Biol. Med., 1907, 4, 35 (secondary peristalsis of oesophagus). MILLER
and SHERRINGTON, Q. J. Exp. Phys., 1915-16, 9, 147 (reflex deglutition
in decerebrate animal). STILES, Am. J. Phys., 1901, 5, 338 (rhythmic
activity of oesophagus). STUART (T. P. ANDERSON), J. Phys., 1907, 35,
446 (epiglottis).
Stomach Movements. — AUER (J.), Am. J. Phys., 1908, 23, 165 (rabbit).
CANNON (W. B.), ib., 1911, 29, 250 (nature of gastric peristalsis); ib., 29,
267 (receptive relaxation). CARLSON, ib., 1912, 31, 151; ib., 1913, 32,
245 (empty stomach of man). HERTZ, Q. J. Med., 1910, 3, 373 (man).
Roux and BALTHAZARD, Arch, de Physiol., 1897, 85 (x-rays).
Innervation of Stomach.— AUER (J.), Am. J. Phys., 1910, 26, 334. BRUNE-
MEIER and CARLSON, ib., 1915, 36, 191 (reflexes from intestinal mucosa to
stomach). CANNON, ib., 1906, 17, 429. LANGLEY, J. Phys., 1898-9,
23, 407 (inhibitory fibres in vagus). MAY (W. P.), J. Phys., 1904, 31, 260.
Rogers, Am. J. Phys., 1917, 42, 605 (r:flex control of gastric vagus tone).
Sensibility of Stomach. — CARLSON and BRAAFLAADT, Am. J. Phys., 1915, 36,
153. HERTZ, COOK and SCHLESINGER, J. Phys., 1908, 37, 481 (stomach
and intestines). MILLER, J. Phys., 1910, 41, 409.
Pylorus Control. — BOLDYREFF, Pfliijer's Arch., 1907, 121, 13. CANNON,
Am. J. Phys., 1904, 12, 387; ib., 1907, 20, 283; ib., 1908, 23, 105 (acid
control). CATHCART, J. Phys., 1911, 42, 433. MORSE, Am. J. Phys.,
1916, 41, 439 (acid control). HEDBLOM and CANNON, Am. J. Med. Sci.,
Oct., 1909.
Movements of Intestines. — ALVAREZ, Am. J. Phys., 1914, 35, 177; ib., 1915,
37, 267 (rhythm of segments from different parts of intestine) ; J. Am. Med.
Ass., 1915, 65, 383. BAYLISS and STARLING, J. Phys., 1900, 26, 107, 125.
CANNON, Am. J. Phys., 1902, 6, 251; 1911, 29, 238; 1912, 30, 114 (tonus
and antiperistalsis) ; J. Am. Med. Ass., 1912, 59, i (large intestine); Arch.
Int. Med., 1911, 8, 417 (importance of tonus). ELLIOTT and BARCLAY-
SMITH, J. Phys., 1904, 31, 272; Hertz and Newton, J. Phys., 1913-14,
47, 57; LYMAN, Am. J. Phys., 1913, 32, 61 (colon). HAMBLETON, Am.
J. Phys., 1914, 34, 446 (movements ofvilli). HERTZ, J. Phys., 1913, 47,
54 (ileo-colic sphincter). MAGNUS, Pnujer's Arch., 1904, 102, 123, 349;
ib., 103, 515, 525; ib., 1906, 111, 152 (surviving intestine). MELTZER
and AUER, Am. J. Phys., 1907, 20, 259 (peristaltic rush).
Innervation of Intestine. — BUNCH, J. Phys., 1898, 22, 357; ib., 1899, 25, 22.
CANNON, Am. J. Phys., 1906, 17, 429. LANGLEY and MAGNUS, J. Phys.,
1905-6, 33, 34-
Defeecition. — CHARLES, Brit. Med. J., Sept. 30, 1899; FRANKL-HOCHWART and
FKOHLICH, Pflvijer's Arch., 1900, 81, 420 (tonus and innervation of anal
sphincters). HERTZ, Sensibility of the Alimentary Canal, 1911.
Vomiting: Emetics. — BROOKS and LUCKHARDT, Am. J. Phys., 1915, 36,
104 (blood-prsssure during vomiting) . EGGLESTON and HATCHER, J . Pharm.
Exp. Ther., 1915, 7, 225. MAGNUS, Ergeb. d. Physiol., 1903, 64 s.
MILLER (F. R.), Pflujer's Arch., 1912, 143, i; Am. J. Phys., 1915, 38,
240 (cardiac inhibition during vomiting).
DIGESTION
CHEMICAL PHENOMENA OF DIGESTION.
BOLDYREFF, Cj. J. Exp. Phys., 1916, 10, 175. GREENWOOD and SAUNDERS,
J. Phys., 1894, 16, 441 (protozoan digestion). LONDON, Z. Physiol. Ch.,
1905, 45, 381; ib., 1906, 47, 368 (protein digestion); ib., 1907, 51, 241;
ib., 1908, 56, 512 (carbohydrate digestion). PAWLOW, Work of the
Digestive Glands, London, 1910; Ergeb. d. Physiol. (Bioch.), 1902,
246 (physiological surgery of digestive canal). SHAW, Am. J. Phys.,
1913, 31, 439 (in birds — chick).
Catalysis, Catalysers. — BREDIG, Anorganische Fermente; Bioch. Z., 1907,
6, 283. BERG and GIES, J. Biol. Ch., 1906, 2, 489 (ions and catalysis).
BROWN (O. H.), Am. J. Phys., 1905, 13, 427. EULER, Z. f. Physiol. Ch.,
1905, 45, 420. KASTLE and LOEVENHART, Am. Chem. J., 1903, 29, 397.
563. LOEVENHART, Am. J. Phys., 1905, 13, 171 (H^O^. NEILSON and
TERRY, Am. J. Phys., 1905, 14, 248. DAKIN, J. Biol. Ch., 1909, 7, 49
(catalytic action of amino-acids, etc.). TAYLOR, ib., 7, 49; ib., 1910. 8, 503.
ENZYMES OR FERMENTS.
ARMSTRONG (H. E. and E. F.), Proc. Roy. Soc. (Lond.), 1907, B 79, 360
(nature of enzymes). ARMSTRONG and ORMEROD, ib., B 78, 376 (lipase).
BAYLISS, Nature of Enzyme Action, 1908; J. Phys, 1913, 46, 236; ib.,
1915, 50, 85 (enzyme action). BEARN and CRAMER, Bioch. J., 1907, 2,
174 (zymoids). BREDIG, Ergeb. d. Phys. (Bioch.), 1902, 134. BUNZEL,
J. Biol. Ch., 1915, 20, 697 (alfalfalaccase). BUCHNER, Arch. f. Phys., 1906,
548 (in micro-organisms). CROFT HILL, Brit. Med. J., June 20, 1903
(reversibility of maltase action). COLE (S. W.), J. Phys., 1904, 30, 281;
MATHEWS and GLENN, J. Biol. Ch., 1911, 9, 29; OSBORNE (W. A.), Z. f.
Physiol. Ch., 1899, 28, 399 (invertase). FALK (K. G.), J. Biol. Qh., 1917,
28, 389; VAN SLYKE and CULLEN, J. Biol. Ch., 1914, 19, 141 (mode of
action of urease and of enzymes in general). FISCHER (E.), Ber. Deutsch.
Chem. Ges., 28, 1429; Zentralb. Physiol., 10, 117 (configuration and
enzyme action). EULER, Ergeb. d. Phys., 1907, 239 (synthesis by ferments) ;
ib., 187 (chemistry). MUTCH, J. Phys., 1912, 44, 176 (histozym).
MICHAELIS and EHRENREICH, Bioch. Z., 1908, 9, 283 (adsorption analysis
of ferments). PAVY and BYWATERS, J. Phys., 1910, 41, 168. PETERS,
J. Biol. Ch., 1908, 5, 367 (adsorption of diastase and catalase). PORTER
(A. E.), Q. J. Exp. Phys., 1910, 3, 375 (inactivation of enzymes). OPPEN-
HEIMER, Ferments and their Actions, translated by Mitchell. S6RENSON,
Bioch. Z., 1907, 7, 45; ib., 1909, 22, 352.
Action of Substances on Ferments. — BIERRY, J. Phys. Path. Gen., 1912, 14,
253 (electrolytes in diastatic actions). COLE (S. W.), J. Phys., 1904, 30, 202
(acid on saliva) . MORSE, J. Biol. Ch., 1915, 22, 125 (halogens). NEILSON
and BROWN, Am. J. Phys., 1904, 10, 225, 335 (ions). QUINAN, J. Biol.
Ch., 1909, 6, 53 (hydroxyl-ion concentration and diastatic hydrolysis).
Enzyme Syntheses. — BRADLEY and KELLERSBERGER, J. Biol. Ch., 1912, 13,
425 (diastase and starch). BRADLEY, ib., 1912, 13, 431 (lactase of mammary
gland). TAYLOR (A. E.), ib., 1908, 3, 87 (trypsin and protein).
Proteolytic Enzymes. — CATHCART, J. Phys., 1905, 32, 299 (spleen enzyme)-
DAKIN, ib., 1903, 30, 84 (kidney enzyme). EFFRONT, Biochemical Cataly-
sis in Life and Industry, Proteolytic Enzymes (translated by Prescott),
1917. FRANKEL, J, Biol. Ch., 1916, 26, 31 (action on purified proteins).
HEDIN, J. Phys., 1904, 30, 155, 195. LEVENE and STOOKEY, Am. J. Phys.,
1904, 12, i (interaction of). KOBER, J. Biol. Ch., 1911, 10, 9 (method).
OPIE and BARKER, J. Exp. Med., 1907, 9, 207 (leucoprotease). SHACKLES
and MELTZER, Am. J. Phys., 1909, 25, 81 (effect of shaking). ROAF, Bioch.
J., 1908, 3, 188 (coldrimetric method). SLOAN, Am. J. Phys., 1917, 42,
568 (origin of proteoly tic ferments) .
Lipases. — ARTHUS, J. Phys. Path. Gen., 1902, 4, 56, 455 (lipase of blood).
BOLDYREFF, Z. Physiol. Ch., 1906-7, 50, 394 (lipase of intestinal juice).
BRADLEY, J. Biol. Ch., 1910, 8, 251 (lipase reactions). CONNSTEIN,
1172 BIBLIOGRAPHY
Ergeb. d, Phys. (Bioch.), 1904, 194- FALK, J. Biol. Ch., 19!?. 31, 07-
HULL and KEETON, J. Biol. Ch., 1917, 32, 127 (gastric lipase). LOEVEN-
HART, J. Biol. Ch., 1906, 2, 391; ROSENHEIM, J. Phys., 1910, 40, p. xiv
(co-emyme of lipase). LOEVENHART, J. Biol. Ch., 1906, 2, 427 (identity
of Upases); Am. J. Phys., 1902,6,331 (lipase andfat metabolism) . LONDON,
Z. f. Phys. Ch., 1906-7, 50, 125. JOBLING, EGGSTEIN and PETERSEN,
J. Exp. Med., 1915, 22, 707 (serum ester ase). MENDEL and LEAVENWORTH,
Am. j. Phys., 1908, 21, 95 (lipase in embryonic tissues). MELLANBY and
WOOLLEY. J. Phys., 1914, 48, 287; SHAW-MACKENZIE, J. Phys., 1915,
49, 216; D:; SOUZA, Bioch. J., 1916, 10, 108 (pancreatic lipase). QUINAN,
J. Med. Res., 1915, 32, 45 (tissue esterases). VON HESS, J. Biol. Ch., 1911,
10, 381 (relation of pancreas to blood and lymph lipase).
Anliferments. — BAYLISS, J. Phys., 1912, 43, 455 (anti-emulsin) . CATHCART,
J. Phys., 1904, 31, 497 ; JOBLING and PETERSEN, J. Exp. Med., 1914, 19,
459; WEIL. Arch. Int. Med., 1910, 5, 109 (serum antitrypsin). EULER,
Ergeb. d. Physiol., 1907, 229. HAMILL, J. Phys., 1906, 33, 479. JOBLING
and PETERSEN, J. Exp. Med., 1914, 20, 452 (bacterial). LANGENSKJOLD,
Skand. Arch., 1914, 31, i. WEINLAND, Z. f. Biol., 1902, 43, 86; 44, i
(tape-worm) .
SALIVARY DIGESTION.
CANNON and DAY, Am. J. Phys., 1903, 9, 396 (in stomach). MAXWELL,
Bioch. J., 1915, 9, 323 (salivary and gastric digestion).
Diastase in Saliva. — CARLSON and RYAN, Am. J. Phys., 1908, 22, i (cat).
EVANS, J. Phys., 1912, 44, 191 (amylo-clastic action of saliva). CHITTEN-
DEN and RICHARDS, Am. J. Phys., 1898, 1, 461 (man). MENDEL and
UNDERHILL, J. Biol. Ch., 1907, 3, 135 (dog). PALMER, Am. J. Phys.,
1916, 41, 483 (ox). SEYMOUR, Am. J. Phys., 1917, 43, 577 (horse).
Secretion of Saliva. — ASHER and CUTTER, Z. f . Biol., 1900, 40, 535. BARCROFT,
J. Phys., 1900, 25, 479 (movement of water in secretion). BUNCH, J. Phys.
1907, 36, i (changes in volume of submaxillary during activity). CARLSON
and McLEAN, Am. J. Phys., 1908, 20, 457 (O2 supply and secretion).
CARLSON, GREER and BECHT, Am. J. Phys., 1907, 20, 180 (blood-supply
and character of saliva) . CARLSON and CRITTENDEN, ib., 1910, 26, 169;
RYAN (J. G.), ib., 1909, 24, 234 (piyalin concentration). DEMOOR, Arch.
Intcrnat. de Phys., 1913, 13, 187. GRUNBAUM (O. F. F.), J. Phys.,
1898, 22, 385 (resistance to secretion and percentage of salts). HENDER-
SON (V. E.), J. Pharm. Exp. Ther., 1910, 2, i (action of drugs). LANGLEY,
J. Phys., 1885, 6, 71; ib., 1888, 9, 55; ib., 1890, 11, 123 (paralytic secre-
tion); 1916, 50, p. xxvi (trophic secretory fibres). JAPELLI, Z. f. Biol.,
1906, 48, 398 (physico-chemical conditions). LATIMER and WARREN,
j. Exp. Med., 1897, 2, 465 (zymogen of ptyalin). MATHEWS (A. P.), Am.
J. Phys., 1901, 4, 482 (atropin). PAWLOW, Ergeb. d. Physiol., 1904,
177 (psychical secretion); Arch. Internal, de Phys., 1904, 1, 119.
WERTHEIMER and BATTEZ, J. Phys. Path. Gen., 1914, 6, 438.
Salivary Glands and Gastric Juice. — HEMMETER, Bioch. Z., 1908, 11, 238.
SWANSON, Am. J. Phys., 1917, 43, 205. HYDE, Z. f. Biol., 1897, 35, 459
(Octopus macropits).
GASTRIC DIGESTION.
Gastric Juice. — CARLSON, Am. J. Phys., 1915, 37, 50 (secretion in man).
CARLSON, HAGAR and ROGERS, ib., 1915, 38, 248 (chemistry of normal
human gash- ic juice) . COHNHEIM and SOETBEER, Z. f . Physiol. Ch., 1902-3,
37, 467; GMELIN, Pfluger's Arch., 1904, 103, 618 (secretion of new-born).
EDKIN.S, J. Phys., 1906, 34, 133; EDKINS and TWEEDY, ib., 1909. 38, 263
(chemical mechanism of gastric secretion). HAMBURGER (W. W.), J.Exp.
Med., 191 T. 14, 535 (pepsin and so-called antipepsin). HARVEY (B. C. H.),
Am. J. Anat., 1907, 6, 207 (gastric glands). PORTER (A. E.), J. Phys.,
1911, 42, 389 (pepsin and rennet are independent). ROGERS, RAHE,
FA\VCETT and HACKETT, Am. J. Phys., 1916, 39, 345 (effect of organ ex-
tracts on gastric secretion).
DIGESTION 1173
Quantitative Relations of Pepsin Action. — HUPPERT (and S-&CHTZ), Pfliiger's
Arch., 1900, 80, 470. NEILSON and BONNOT, Arch. Int. Med., 1913,
11. 395- SPRIGGS, Z. f. Physiol. Ch., 1902, 35, 465.
HC1 of Gastric Juice. — FLEIG, J. Phys. Path. Gen., 1908, 10, 1009 (reactions
for). LUSK and FERRIS, Am. J. Phys., 1898, 1, 277 (inversion of cane
sugar by). PALMER, Bioch. J., 1906, 1, 398 (in carcinoma). SJOQVIST,
Skand. Arch. Phys., 1895, 5, 277. WEINLAND, Z. f. Biol., 1910, 55, 58
(in shark). WIDDICOMBE (J. H.), J. Phys., 1902, 28, 175 (digestion of
cane sugar) .
Acidity of Gastric Juice. — MENTEN, J. Biol. Ch., 1915, 22, 341 (in man).
MICHAELIS and DAVFDSOHN, Z. Exp. Path. Ther., 1910, 8, 398. TANGL,
Pfluger's Arch., 1906, 115, 64.
Formation of HC1 of Gastric Juice. — BENSLEY and HARVEY, Trans. Chicago
Path. Soc., 1913, 9, 221. BERGEIM, Soc. Exp. Biol. Med., 1914, 12, 21.
BENRATH and SACHS, Pfliiger's Arch., 1905, 109, 466. KOEPPE, Pfluger's
Arch., 1896, 62, 567. LIEBERMANN, Pfluger's Arch., 1891, 50, 25.
OSBORNE (T. B.), Am. J. Phys., 1901, 5, 180. MONTI, Archivio di Fisiol.,
1913, 11, 155 (function of the delomorphic cells). VON RHORER, Pfluger's
Arch., 1905, 110, 416. WESENER, ib., 1899, 77, 483.
Acidity of Gastric Contents. — FOWLER, BERGEIM and HAWK, Soc. Exp.
Biol. Med., 1916, 13, 58 (indicators). MCCLENDON, Am. J. Phys., 1915,
38, 191 (adults and infants, acidity in stomach and duodenum). MOORE,
ALEXANDER, KELLY and ROAF, Bioch. J., 1906, 1, 274.
Protein Digestion in Stomach. — TOBLER, Z. f. Physiol. Ch., 1905, 45, 185.
ZUNZ (E.), Ergeb. d. Phys., 1906, 622, "663. CHITTENDEN, MENDEL
and JACKSON, Am. J. Phys., 1898, 1, 164 (action of alcohol on digestion).
Proteoses, Albumoses. — CHITTENDEN and HARTWELL, J. Phys., 1891, 12, 12.
HASLAM, ib., 1907, 36, 164 (deutero-albumose) . KttHNE and CHITTENDEN,
Z. f. Biol., 1884, 20, n, 409.
Digestion of Nucleins. — AMBERG and JONES, J. Biol. Ch., 1911, 10, 81.
LEVENE and MEDIGRECEANU, ib., 9, 375.
Chymase (Eennin). — BANG, Z. f. Physiol. Ch., 1904-5, 43, 358. BOSWORTH,
J. Biol. Ch., 1913, 15, 231 ; ib., 1914, 19, 397. BURGE, Am. J. Phys., 1912,
29, 330. EDMUNDS, J. Phys., 1896, 19, 466. FULD., Ergeb. d. Physiol.
(Bioch.), 1902, 468. HAWK, Am. J. Phys., 1903, 10, 37. KENT, J. Phys.,
1911, 43, P- xxiv. LEARY and SHEIB, J. Biol. Ch., 1917, 28, 393. LOCKE,
J. Exp. Med., 1897, 2, 493. LOEVENHART, Z. f. Physiol. Ch., 1904, 41,
177. MELLANBY, J. Phys.r 1912, 45, 345. PAWLOW and PARASTSCHAK,
Z. f. Physiol. Ch., 1904, 42, 415. PORTER (A. E.), J. Phys., 1911, 42, 389.
TAYLOR (A. E.), J. Biol. Ch., 1908, 5, 399. WARREN (J. W.), J. Exp.
Med., 1897, 2, 475-
PANCREATIC JUICE.
BAYLISS and STARLING, J. Phys., 1904, 30, 61. BOLDYREFF, Q. J. Exp. Phys.,
1914, 8, i ; ib., 1916, 10, 175 ; Ergeb. d. Physiol., 1911, 121, 156. BRADLEY,
J. Biol. Ch., 1909, 6, 133 (human). DE ZILWA, J. Phys., 1904, 31, 230
(composition). FISCHER (E.) and ABDERHALDEN, Z. f. Physiol. Ch., 1907,
51, 264 (action on polypeptides). WELKER and FALLS, J. Biol. Ch., 1917,
32, 509 (influence of pancreatic digestion on non-colloidal N-content of
scrum).
Enzymes of Pancreas. — BAYLISS, J. Phys., 1907, 36, 221 (causes of rise of
electrical conductivity in trypsin action). EDKINS, ib., 1891, 12, 218
(action on casein). HEDIN (S. G.), ib., 1905, 32, 468; ib., 1906, 34, 370
(trypsin action). MAGNUS, Z. f. Physiol. Ch., 1906, 48, 376 (synthetic bile
acids and pancreatic fat-splitting). MAYS (K.), ib., 1907, 51, 182.
MELLANBY and WORLEY, J. Phys., 1913, 47, 338 (trypsin, tyypsinogen,
enterokinase); ib., 1913, 46, 159 (Ca and generation of trypsin from tryp-
sincgen). ROBERTSON (T. B.), J. Piol. Ch., 1908, 5, 31 (rdle of alkali i'i
hydrolysis of proteins by trypsin). TERROINE and SCHAEFFER, J. Phys.
II74 BIBLIOGRAPHY
Path. Gen., 1910, 12,884, 965 (trypsin and erepsin) . TERROIXE, ib., 1911,
13, 837 (saponifying ferments) ; ib., 1913, 15, 1125, 1148 (digestion and
absorption of fat). TERROINE and WEILL, ib., 1912, 14, 437 (starch
digestion). VERNOX, J. Phys., 1901, 26, 405 (trypsin); ib., 1910, 47, 325
(trypsinogen autocatalysis); ib., 27, 174 (pancreatic rennin and diastase);
ib., 1902, 28, 448 (zymogens); ib., 1904, 30, 330. ZUNZ, Arch. Internal.
Physiol., 1911, 13, 191 (action on proteins and proteases). RACHFORD,
J. Phys., 1899, 25, 165 (influence of bile); Am J. Phys., 1899, 2, 483.
Secretion of Pancreatic Juice. — VON AXREP, J. Phys., 1914, 49, i; ib., 1916,
50, 421 (vagus). CAMUS and GLEY, Arch. Internat. Phys., 1913, 13, 102
(pilocarpin) . HERRING and SIMPSON, Q. J. Exp. Phys., 1909, 2, 100
(secretory pressure). MAY (O.), J. Phys., 1904, 30, 400 (secretion and
blood supply). ROGERS, RAHE, FAWCETT and HACKETT, Am. J. Phys.,
1916, 40, 12 (effect of organ extracts). WERTHEIMER and BOULET, Arch.
Internat. Phys., 1912, 12, 247.
Secretin. — BAYLISS and STARLING, Ergeb. d. Physiol., 1906, 670; ib., 693
(chemical nature of hormones); J. Phys., 1903, 28, 325; ib., 29, 174.
BAINBRIDGE and BEDDARD, Bioch. J., 1906, 1, 429; EVANS, J. Phys.,
1912, 44, 461 (secretin and diabetes). DELEZENNE, J. Phys. Path. Gen.,
1912, 521, 540. DIXON and HAMILL, J. Phys., 1909, 38, 314. H£DON,
Arch. Internat. Phys., 1912, 12, 485. WERTHEIMER and LEPAGE,
J. Phys. Path. Gen., 1901, 3, 689, 708.
Adaptation in the Digestive Juices. — BAYLISS and STARLING, Ergeb. d. Physiol.,
1906, 681; J. Phys., 1904, 30, 64. PLIMMER (R. H. A.), J. Phys., 1906,
34, 93; ib., 1906, 35, 20 (adaptation of pancreas to lactose).
BILE.
Chemistry of Bile. — BRAND, Pfliiger's Arch., 1902, 90, 491; ROSENBLOOM,
J. Bio.l. Ch., 1913, 14, 241 (human bile). FISCHER (H.), Ergeb. d. Phys.,
1916, 185 (bile and blood pigment). HEYNSIUS and CAMPBELL, Pfliiger's
Arch., 1871, 4, 497; HAYCRAFT and SCOFIELD, Z. f. Physiol. Ch., 1890,
14, 73; STEWART (G. N.), Studies Physiol. Lab., Univ. Manchester, 1891,
201 (bile-pigment spectra). HAMMARSTEN, Ergeb. d. Physiol., 1905, 1.
OKADA, J. Phys., 1915, 50, 114 (reaction). GARDNER and KNOX, J. Phys.,
1907, 36, p. ix (cholesterol in bile). HAMMARSTEN, Z. f. Physiol. Ch.,
1904-5, 43, 127; LEWIS, Bioch. J., 1908, 3, 119; SCHRYVER, J. Phys., 1912,
44, 265 (bile-salts). SELLARDS, J. Exp. Med., 1909,. 11, 786 (reaction with
blood-serum) .
Bile and Bile-Pigment Formation. — WHIPPLE and HOOPER, Am. J. Phys.,
1916, 40, 332; ib., 1917, 42, 256, 544; ib., 1917, 43, 258, 275, 290; J. Exp.
Med., 1913, 17, 612 (from hemoglobin outside the liver).
Bile and Bile Pigment Secretion. — BARBERA, Arch. Ital. Biol., 1902, 38, 447.
BAYLISS and STARLIXG, Ergeb. d. Physiol., 1906, 677. DOYON and
DUFOURT, Arch, de Phys., 1896, 587; ib., 1897, 562. DASTRE, ib., 1890,
800. EIGER, Z. f. Biol., 1915, 66, 229 (vagus influence). HOOPER and
WHIPPLE, Am. J. Phys., 1917, 42, 264, 280 (influence of bile). OKADA,
J. Phys., 1915, 49, 457. PFAFF and BALCH, J. Exp. Med., 1897, 2, 49.
PUGLIESE, Arch. Ital. Biol., 1902, 38, 257. SIMPSON (S.), Soc. Exp. Biol.
Med., 1910, 7, 8.
Eck's Fistula. — BERNHEIM and VOEGTLIN, J. Pharm. Exp. Ther., 1909, 1, 463.
CARREL and GUTHRIE, Compt. Rend. Soc. Biol., June 30, 1906, 1104
(simple method). HAWK, Am. J. Phys., 1908, 21, 259. HERRICK (F. C.),
J. Exp. Med., 1905, 7, 751. SWEET, J. Exp. Med., 1905, 7, 163.
Absorption of Bile, Icterus. — HARLEY, Proc. Roy. Soc., 1892, (paths).
HAROLD, PEPPER and PERRY, J. Exp. Med., 1915, 22, 675. HERRING
and SIMPSON, Proc. Roy. Soc., 1907, B 79, 517 (secretory pressure and
absorption). PEARCE (R. M.) ET AL., J. Exp. Med., 1912, 16, 758, 769,
780 (h&molytic jaundice and the spleen). SUTHERLAND, Bioch. J., 1906,
1, 364. VOEGTLIN and BERNHEIM, J. Pharm. Exp. Ther., 1911, 2, 455.
DIGESTION ii?5
WERTHEIMER and LEPAGE, Arch, de Phys., 1897, 363 (paths of absorp-
tion); ib., 1898, 334; J. Phys. Path. Gen., 1899, 1, 259. WHIPPLE and
HOOPER, J. Exp. Med., 1913, 17, 593 ; 1916, 23, 137. WHIPPLE and KING,
ib., 1911, 13, 115.
Toxicity of Bile. — FROTHINGHAM and MINOT, J. Med. Res., 1912, 27, 79-
KARSNER and EISENBREY, ib., 1912, 26, 357 (antibodies). KING and
STEWART (H. A.), J. Exp. Med., 1909, 11, 573. MELTZER and SALANT,
ib., 1906, 8, 127. TATUM, J. Biol. Ch., 1916, 27, 243 (influence on autoly sis).
Bile Circulation. — STADELMANN, Z. f. Biol., 1897, 34, i. WERTHEIMER, Arch,
de Phys., 1892, 577.
Innervation of Gall-Bladder. — BAINBRIDGE and DALE, J. Phys., 1905, 33, 138.
FREESE, Johns Hopk. Hosp. Bull., 16, June, 1905. LIEB and MC\VHORTER,
Soc. Exp. Biol. Med., 1915, 12, 102.
Bile and Bile-Salts in Digestion. — CHITTENDEN and ALBRO, Am. J. Phys.,
1898, 1, 307 (influence on pancreatic proteolysis) . DE JONGE, Arch.
Neerland. Physiol., 1917, 1, 182. KINGSBURY, J. Biol. Ch., 1917, 29,
367. LOEVENHART and SOUDER, ib., 1906-7, 2, 415- PFLT}GER (E.)(
Pfliiger's Arch., 1902, 90, i. RACHFORD, J. Phys., 1891, 12, 93.
INTESTINAL JUICE.
BAYLISS and STARLING, Ergeb. d. Physiol., 1906, 678 (chemical reflexes).
HAMBURGER and HEKMA, J. Phys. Path. Gen., 1902, 4, 805; ib., 1904, 6,
40 (man). MENDEL, Pfliiger's Arch., 1896, 63, 425 (paralytic secretion).
MOSENTHAL, J. Exp. Med., 1911, 13, 319. PREGL, Pfliiger's Arch., 1895,
61, 359 (sheep). SALASKIN, Z. Physiol. Ck., 1902, 35, 419 (dog).
Ferments. — BLOOD (A. F.), J. Biol. Ch., 1910, 8, 215; COHNHEIM, Z. Physiol.
Ch., 1906, 47, 286; 1902, 35, 134; 36, 13, 244; REED and STAHL, J. Biol.
Ch., 1911, 10, 109; VERNON, J. Phys., 1905, 33, 81 (erepsin). HAMILL,
J. Phys., 1905-6, 33, 476; MELLANBY and WOOLLEY, ib., 1912, 45, 370
Reaction of Intestinal Contents. — MCCLENDON, SHEDLOV and THOMSON,
J. Biol. Ch., 1917, 36, 269 (ileum). MOORE and BERGIN, Am. J. Phys.,
1900, 3, 316.
Digestibility of Foods. — BRYANT and MILNER, Am. J. Phys., 1903, 10, 81
(vegetables). FRANK, J. Biol. Ch., 1911, 9, 463 (egg-white). LANGWORTHY
and HOLMES, U. S. Dept. Agric. Bull., 1917, 505, 507; LANGWORTHY, ib.,
1915, 310; SMITH, MILLER and HAWK, J. Biol. Ch., 1915, 23, 505 (fats).
ROCKWOOD, J. Biol. Ch., 1910, 8, 327 (flour).
Bacteria of Alimentary Canal.— BALDWIN, J. Biol. Ch., 1909, 7, 37. GUSHING
and LIVINGOOD, Johns Hopkins Hosp. Rep., 9, 543. GERHARDT, Ergeb.
d. Physiol. (Bioch.), 1904, 107. HERTER, Harvey Lect., New York,
Nov. 3, 1906. HERTER and KENDALL, J. Biol. Ch., 1909, 6, 499; ib.,
1909, 7, 203 (influence of diet on intestinal flora). KENDALL, J. Med. Res.,
1911, 25, 117. KIANIZIN, J. Phys. Path. Gen., 1911, 13, 689; J. Phys..
1916, 50, 391; NUTTALL and THIERFELDER, Arch. f. Physiol., 1895, 559;
SCHOTTELIUS, Arch. f. Hygiene, 34 (aseptic digestion).
Fseces. — ELLIS and GARDNER, Proc. Roy. Soc., 1912, B 86, 13 (excretion of
cholesterol).
CHAPTER VII.
ABSORPTION.
Adsorption. — BARRETT and EDIE, Bioch. J., 1907, 2, 443. BAYLISS, ib., 1906,
1,175. HEDIN, ib., 1907, 2, 112 (of enzymes). HOFMANN, Zentr. f . Phys.,
1910, 24, 805. MICHAELIS and RONA, Bioch. Z., 1908, 15, 196. ROBERT-
SON, J. Biol. Ch., 1908, 4, 35. VAN SLYKE, ib., 1908, 4, 259.
Diffusion.— DENIS (W.), Am. J. Phys., 1906, 17, 35 (salts of blood). FLEXNER
and NOGUCHI, Soc. Exp. Biol. Med., 1906, 3, 66. HEDIN, Pfliiger's Arch.,
1899, 78, 205. HOBER, ib., 1898, 71, 624 (in intestinal absorption); ib.,
1 1 76 BIBLIOGRAPHY
1899, 74, 225. MEYER, Hofmeister's Beit., 1906, 7, 393- REID (W.),
J. Phys., 1897, 21, 85; MINES, ib., 1911, 42, p. xxviii (method). VOIGT-
LANDER, Z. f. Physikal. Ch., 1889, 3, 316.
Imbibition. — FISCHER and MOORE, Am. J. Phys., 1907, 20, 330. HENDERSON,
PALMER and BECHT, J. Pharm. Exp. Ther., 1914, 5, 449 (H-ion concen-
tration). OSTWALD (W.), Pfliigcr's Arch., 1905, 108, 563; 109, 277; ib.,
1906, 111, 581.
Surface Tension. — BEARD and CRAMER, Proc. Roy. Soc., 1915, B 88, 575 (and
ferment action). CRAMER, ib., 688,584 (and cell metabolism). MACALLUM
(A. B.), Efgeb. d. Physiol., 1911, 11, 598; Proa Roy. Soc., 1913, B 86, 527.
TRAUBE, Pfliiger's Arch., 1904, 105, 559 (surface tension and vital pheno-
mena) .
Mechanism of Absorption. — MUNK, Ergeb. d. Phys. (Bioch.), 1902, 296.
OVERTON, Nagel's Handb. d. Physiol., Bd. ii., 2, 744. SCOTT and DENIS,
Am. J. Phys., 1913, 32, i (dog-fish). HAMBURGER, Arch. f. Phys., 1896,
302, 428 (intra-intestinal and infra-abdominal pressure and absorption).
Absorption from Intestine. — BRODIE and VOGT, J. Phys., 1910, 40, 135 (gaseoui
exchange of intestine and absorption). BRODIE, CULLIS and HALLIBURTON,
ib., 1910, 40, 173. COHNHEIM, Z. f. Biol., 1896, 33, 9; ib., 37, 443; 38, 419;
39, 167. DAKIN, J. Biol. Ch., 1908, 4, 437 (isomeric substances) . HANZLIK
and COLLINS, J. Pharm. Exp. Ther., 1913, 5, 185 (alcohol). LONDON ET
AL., Z. f. Physiol. Ch., 1906, 49, 324, 328. WALLACE and CUSHNY, Am.
J. Phys., 1898, 1, 411. REACH, Pfliiger's Arch., 1901, 86, 247 (compara-
tive absorption in large and small intestine). REID, J. Phys., 1898, 22,
p. Ivi.; ib., 1900-1, 26, 436 (nerves and absorption); ib., 1896,20, 298.
HEIDENHAIN, Pfliiger's Arch., 1894, 56, 579 (serum). RAVENEL and
HAMMER, J. Med. Res., 1911, 24, 513 (bacteria). COLEMAN and GEPHART,
Arch. Int. Med., 1915, 15, 882 (in fever).
Absorption from Peritoneum. — ADLER and MELTZER, J. Exp. Med., 1896, 1,
482. BUXTON, J. Med. Res., 1907, 16, 17. FLEISHER and LOEB,
J. Exp. Med., 1910, 12, 288, 487, 510. MELTZER, J. Phys., 1898, 22, 196.
SHIPLEY and CUNNINGHAM, Am. J. Phys., 1916, 40, 75. STARLING, J. Phys.,
1898, 22, p. xxiv. WELLS and MENDEL, Am. J. Phys., 1907, 18, 156.
Absorption from Connective Tissue. — HAMBURGER, Bioch. Z., 1907, 3, 359-
MELTZER and AUER, J. Exp. Med., 1905, 7, 59', 1911, 13, 328 (intramuscular
tissue). STARLING, J. Phys., 1895-6, 19, 312.
Absorption by Skin (Frog). — MAXWELL, Am. J. Phys., 1913, 32, 286.
Absorption of Fat. — BLOOR, J. Biol. Ch., 1912, 11, 429; 1913, 15, 105; 1913,
16, 517; 1915, 23, 317. HARLEY, J. Phys., 1895, 18, i (effect of pancrea-
tectomy). GREENE and SKAER, Am. J. Phys., 1913, 32, 358. GREENE,
ib., 1912, 30, 278 (salmon). MENDEL and BAUMANN, J. Biol. Ch., 1915,
22, 165 (from stomach). McCLURE, VINCENT and PRATT, Am. J. Phys.,
1917, 42, 596 (pancreatectomy); J. Exp. Med., 1917, 25, 381. MOORE and
ROCKWOOD, J. Phys., 1897, ,21, 58. MUNK, Zentr. f. Phys., 13, 657; 14,
121, 153, 409; 15, 297. PLANT, Am. J. Phys., 1908-9, 23, 65. PFLUGER
(E.), Pfliiger's Arch., 1900, 82, 303; 1902, 88, 299, 431. MENDEL, Am. J.
Phys., 1909, 24, 493 (stained fat) ; J. Biol. Ch., 1912, 13, 71. WHITEHEAD,
Am. J. Phys., 1909, 24, 294; ib., 1910, 25, p. xxviii (stained fat).
Absorption of Cholesterol.— CORPER, J. Exp. Med., 1915, 21, 179. FRASER
and GARDNER, Proc. Roy. Soc., 1909, B 81, 230. LEHMAN, J. Biol. Ch.,
1913, 16, 495. MUELLER, J. Biol. Ch., 1916, 27, 463.
Absorption of Proteins. — CATHCART and LEATHES, J. Phys., 1905-6, 33, 462.
COHNHEIM, Z. f. Physiol. Ch., 1902, 35, 396, 416 (octopods)', ib., 1906,
49, 64. FOLIN and DENIS, J. Biol. Ch., 1913, 14, 453; ib., 1912, 12, 253
(large intestine). MENDEL, Am. J. Phys., 1899, 2, 137 (paths). MUNK,
Zentralb. f. Phys., 1907, 11, 585 (paths). REID, J. Phys., 1895-6, 19, 240
(peptones). NOLF, J. Phys. Path. Gen., 1907, 9, 925, 957. SALASKIX,
Z. f. Physiol. Ch., 1907, 51, 167 (stomach). FOLIN and LYMAN, J. Biol.
Ch., 1912, 13, 389 (stomach); ib., 1912, 12, 259. LONDON, Z. f. Physiol.
Ch., 1909, 62, 448.
FORMATION OF LYMPH 117?
Albumoses in Tissues and Blood. — ABEL, PINCOFFS and ROUILLER, Am. J.
Phys., 1917, 44, 320. EMBDEN and KNOOP, Hofmeister's Beit., 1903, 3,
120. LANGSTEIN, ib., 3, 373. SCHUMM, ib., 1904, 4, 453.
Absorption of Sugars. — HE DON, Arch, de Pharmacod., 1900, 7, 163. MUNK,
Arch. f. Phys., 1890, 376 (paths for sugar, protein, fat). REACH, Arch.
Exp. Path. Pharm., 47, 231 (by rectum). REID, J. Phys., 1901, 26, 427;
1902, 28, 241. ROHMANN and NAGANO, Pfliiger's Arch., 1903, 95, 533.
Absorption of Iron. — ABDERHALDEN, Z. f. Bioi., 1900, 39, 113, 193. BUNGE,
Z. f. Physiol. Ch., 1898, 25, 36. HALL (W. S.), Arch. f. Phys., 1896,
49; ib., 1894, 455. MEYER, Ergeb. d. Phys., 1906, 698. SATTLER, Arch.
Exp. Path. Pharm., 1905, 52, 326.
CHAPTER VIII.
FORMATION OF LYMPH.
Lymphatic System. — JOB, Anat. Record, 1915, 9. MACCALLUM (W. G.), Arch,
f. Anat. (u. Physiol.), 1902, 273 (relation of lymphatics to connective tissue).
SABIN (F. R.), Ergeb. d. Anat. u. Entwick., 1913; Am. J. Anat., 1904,
3, 183 (origin of lymphatic system).
Lymph Formation. — ASHER and BARBERA, Z. f. Biol., 1898, 36, 154. ASHER
and BUSCH, Z. f. Biol., 1900, 40, 333. ASHER, Z. f. Biol., 1899, 37, 261.
ASHER and GIES, Z. f. Biol., 1900, 40, 180. BAINBRIDGE, J. Phys., 1906,
34, 275 (post-mortem); J. Phys., 1900-1, 26, 79 (submaxillary gland);
ib., 28, 204 (liver); ib., 32, i (pancreas). BRANDE and CARLSON, Am. J.
Phys., 19, 221 (lymphagogues and agglutinins in serum and lymph).
CUTTAT-GALIZKA, Z. f. Biol., 1911, 56, 309 (post-mortem). COHNSTEIN,
Pfluger's Arch., 1895, 59, 350, 508; ib., 1895, 62, 58; Arch. f. Phys., 1896,
379. CARLSON, GREER and BECHT, Am. J. Phys., 1907, 19, 360 (salivary
glands); ib., 22, 104 (lymphagogue action of lymph). DIXON (R. L.), J.
Exp. Med., 1912, 16, 139. ELLINGER, Ergeb. d. Phys. (Bioch.), 1902,
355. HAMBURGER (H. J.), Arch. f. Phys., 1895, 364 (resuir.e of H eiden-
hain'sview);ib., 1897, 132. JAPELLI, Z.f. Biol., 1910, 53, 319. LAZARUS-
BARLOW, J. Phys., 1895-6, 19, 418 (osmosis and filtration). LEATHES,
J. Phys., 19, i. MENDEL and HOOKER, Am. J. Phys., 1902, 7, 380
(strawberry extract). MENDEL, J. Phys., 19, 227. MTJLLER, Pfluger's
Arch., 1908, 122, 455 (Tannenberg bodies). OPIE, J. Exp. Med., 1912,
16, 831 (lymph formation and oedema of liver). PUGLIESI, Arch. Ital.
Biol., 1902, 38, 422. SCOTT (F. H.), J. Phys., 1915-16, 50, 159; SCOTT,
HERMAN and SNELL, Am. J. Phys., 1917, 44, 313; SCOTT, Am. J. Phys.,
1917, 44, 298. SIHLER, J. Exp. Med., 1900, 5, 493. STARLING, J. Phys.,
1894-5, 17, 30; WERTHEIMER, J. Phys. Path. Gen., 1906, 8, 806 (work of
glands and lymph formation). YANAGAMA, J. Pharm. Exp. Ther., 1916
9,75-
(Edema.- — BOLTON, Proc. Roy. Soc., 1907, B 79, 267 (by obstruction of vence
caves and portal). FISCHER (M.), (Edema, 1910. FLEISHER, HOYT and
LOEB (L.), J. Exp. Med., 1909, 11, 291. LAZARUS-BARLOW, Phil. Trans.
Roy. Soc., 1894, 185, 779 (accompanying passive congestion). MELTZER,
Amer. Medicine, 1904, 8. MILLER (J. L.) and MATTHEWS (S. A.), Arch!
Int. Med., 1909, 4, 356 (pulmonary). MOORE (A. R.), Pfluger's Arch.,
1912, 147, 28; Am. J. Phys., 1915, 37, 220. PEARCE (R. M.), Arch.
Int. Med., 1909, 3, 422. WOOLLEY, J. Lab. Clin. Med., 1956, 1, 267
(nervous influences and).
CHAPTER IX
EXCRETION.
COMPOSITION OP URINE.
BOUCHEZ, J. Phys. Path. Gen., 1912, 14, 46, 74. CAMERER, Z. f. Biol.,
1904, 45, i; FOLIN, Am. J. Phys., 1905, 13, 45, 66 (normal urines).
CATHCART, Bioch. Z., 1907, 6, 109 (in starvation).
1178 BIBLIOGRAPHY
Total Nitrogen Excretion in Normal Persons. — BARRINGER (T. B. and B. S.),
Am. J. Phys., 1910, 27, 119-
Urea in Urine. — MARSHALL, J. Biol. Ch., 1913, 14, 283 ; ib., 15, 495 ; VAN SLYKE
and CULLEN, ib., 1914, 19, 211. VAN SLYKE, ib., 1916, 24, 117 (deter-
mination by urease method).
Ammonia in Urine. — FOLIN and BELL, J. Biol. Ch., 1917, 29, 329 (colorimetric
determination). FOLIN and MACALLUM, ib., 1912, 11, 523 (determination).
Acidity of Urine. — HENDERSON (L. J.) and PALMER, J. Biol. Ch., 1912, 13,
393; ib., 14, 81. HENDERSON and SPIRO, Bioch. Z., 1908, 15, 105.
Phenols.— DUBIN, J. Biol. Ch., 1916, 26, 69 (physiology of). FOLIN and DENIS,
ib., 507 (relative excretion of, by kidneys and intestine).
Uric Acid Excretion. — BENEDICT and HITCHCOCK, J. Biol. Ch., 1915, 20, 619;
FOLIN and DENIS, ib., 1912, 13, 363, 469 (colorimetric estimation of uric
acid in urine). HANZLIK and HAWK, ib., 1908, 5, 355 (normal men).
LEATHES, J. Phys., 1906, 35, 125 (diurnal and nocturnal variations).
MENDEL and BROWN, J. Am. Med. Ass., 1907, 49, 896 (rate in man).
MENDEL and STEHLE, J. Biol. Ch., 1915, 22, 215 (rdle of digestive glands in
excretion of endogenous). ROCKWOOD, Am. J. Phys., 1904, 12, 38
(endogenous). WELLS (H. G.), J. Biol. Ch., 1916, 26, 319 (accumulation
in tissues in suppression of urine) .
Alkaptonuria. — DAKIN, J. Biol. Ch., 1911, 9, 151. GARROD and HARTLEY,
J. Phys., 1907, 36, 136. GARROD and HELE.I&., 1905-6, 33, 198. GARROD
and CLARKE, Bioch. J., 1907, 2, 217. RA WOLD and WARREN, J. Biol.
Ch., 1909, 7, 465. SCHULZ, Ergeb. d. Physiol. (Bioch.), 1903, 180.
Bile-Salts in Urine. — ALLEN, J. Biol. Ch., 1915, 22, 505 (Hay's surface tension
method). GR^NBAUM, J. Phys., 1904, 30, p. xxvi.
Bile-Pigments in Urine. — HAMMARSTEN, Skand. Arch. Phys., 9, 313. JOLLES
(A.), ib., 10, 338; Pfliiger's Arch., 1899, 75, 446. MUNK, Arch. f. Phys.,
1898, 361. SCHULZ, Ergeb. d. Physiol. (Bioch.), 1903, 174.
Proteinuria. — CAMERON and WELLS, Arch. Int. Med., 1915, 15, i^', CLOETTA,
Arch. Exp. Path. Pharm., 1899, 42, 453 (origin of the proteins). FOLIN
and DENIS, J. Biol. Ch., 1914, 18, 273; MARSHALL, BANKS and GRAVES,
Arch. Int. Med., 1916, 18, 250 (estimation of the proteins) . SIKES, J. Phys.,
1905-6, 33, 101 (the globulin of" albuminous " urine).
Ammo-Acids in Urine. — BENEDICT and MURLIN, J. Biol. Ch., 1913, 16, 365
(determination of amino-acid nitrogen). FORSSNER, Z. f. Physiol. Ch.,
1906, 47, 15- HALL (I. W.), Bioch. J., 1906, 1, 241. LEVENE and VAN
SLYKE, J. Biol. Ch., 1912, 12, 301 ; VAN SLYKE, ib., 1913, 16, 125 (estima-
tion). MUTCH, J. Phys., 1914, 49, p. ii.
Pentosuria. — LEVENE and LA FORGE, J. Biol. Ch., 1913, 15, 481 ; ib., 1915, 18,
319 (note on a case). NEUBERG, Ergeb. d. Physiol. (Bioch.), 1904, 373
(physiology of pentoses and glycuronic acid).
Heematoporphyrin in Urine. — GARROD, J. Phys., 1892, 13, 598; ib., 1894, 15,
108; ib., 1894-5, 17, 349. SCHULZ, Ergeb. d. Physiol., 1903, 162.
SECRETION OF URINE.
CUSHNY, The Secretion of Urine, Londpn, 1917; J. Phys., 1901-2, 27, 429;
J. Phys., 1917, 51, 36 (excretion of urea and sugar). BAINBRIDGE and
BEDDARD, Bioch. J., 1906, 1, 255 (secretion by renal tubules in frog).
BAINBRIDGE, MENZIES and COLLINS, J. Phys., 1914, 48, 233 (urine forma-
tion in frog). BARCROFT and STRAUB, ib., 1910, 41, 145. BARCROFT and
PIPER, ib., 1915, 49, p. xiii (in decerebrate animals). BEDDARD, ib., 1902,
28, 20 (ligation of renal arteries in frog). BOYD, ib., 1902, 28, 76 (extirpa-
tion of renal medulla). BRODIE and CULLIS, ib., 1906, 34, 224. BRODIE
and MACKENZIE (J. J.), Proc. Roy. Soc., 1914, B 87, 594 (changes in
glomeruli and tubules accompanying activity). BRODIE, ib., 87, 571
(glomerular function) . Cow (D.), J. Phys., 1914, 48, i. CULLIS (C.),
J. Phys., 1906, 34, 250; ib., 1908, 87, p. x\~i*(frog). FOLIN and DENIS,
EXCRETION 1179
J. Biol. Ch., 1915, 22, 321 (selective activity of human kidney). HASKINS,
Am. J. Phys., 1904, 10, 362; HATCHER and SOLLMANN, ib., 1903, 8, 139
(in salt-hunger). VON FURTH, Ergeb. d. Physiol. (Bioch.), 1902, 395
(urine secretion of lower animals). KNOWLTON (F. P.), J. Phys., 1911,
43, 219 (influence of colloids). ISAACS (R.), Am. J. Phys., 1917, 45, 71
(reaction of kidney colloids and renal function) . LINDEMANN, Z. f. Biol.,
1901, 42, 161 (elimination of glomeruli). GESELL, Am. J. Phys., 1913,
32, 70. HOOKER, ib., 1910, 27, 24 (relation of pulse pressure to renal
secretion). MACALLUM and BENSON, J. Biol. Ch., 1909, 6, 87 (composition
of dilute renal excretions) . MAGNUS, Arch. Exp. Path. Pharm., 1901, 45,
201 (in plethora). QUINBY, Am. J. Phys., 1917, 42, 593; J. Exp. Med.,
1916, 23, 535 (denervated kidney). RICHARDS and PLANT, Am. J. Phys.,
1917, 42, 592 (blood-pressure and urine formation). SOLLMANN, Am. J.
Phys., 1902, 8, 155. SOLLMANN and BROWN, J. Exp. Med., 6, 207
(injection of egg-albumin, etc.). SOLLMANN, Am. J. Phys., 1905, 9, 425
(chlorides of urine). DE SotrzA, J. Phys., 1900, 26, 139 (effects of venous
obstruction). SPIRO and VOGT, Ergeb. d. Physiol. (Bioch.), 1902, 414.
SPIRO, Arch. Exp. Path. Pharm., 1898, 41, 148 (action of artificial concen-
tration of the blood). SHARPE, Am. J. Phys., 1912, 31, 75 (in birds).
STARLING, J. Phys., 1899, 24, 317 (glomerular function) . UNDERBILL,
WELLS and GOLDSCHMIDT, J. Exp. Med., 1913, 18, 347 (renal secretion
during tartrate nephritis) .
Perfusion of Eicised Kidneys. — RICHARDS and PLANT, J. Pharm. Exp. Ther.,
1915, 7, 485. SOLLMANN (T.), Am. J. Phys., 1905, 13, 241; ib., 1907,
19, 233; ib., 1908, 21, 37. WILLIAMS, ib., 1907, 19, 252.
Excretion of Pigment by the Kidney. — CARTER (W. S.), J. Am. Med. Ass.,
Nov. 21, 1903, p. 1248. GURWITSCH, Pfliiger's Arch., 1902, 91, 71. H6BER
and KEMPNER, Bioch. Z., 1908, 11, 105. HOBER and KONIGSBERG,
Pfliiger's Arch., 1905, 108, 323. SHAFFER (G. D.), Am. J. Phys., 1908,
22, 335- SOBIERANSKI, Pfliiger's Arch., 1903, 98, 135.
Acid Secretion of Kidney. — CUSHNY, J. Phys., 1904, 31, 188. DRESER,
Hofmeister's Beit., 1905, 6, 178. HENDERSON and PALMER, J. Biol. Ch.,
1914,17,305. HENDERSON (L. J.), ib., 1911, 9, 403. TREVAN, J. Phys.,
1916, 50, 265.
Reabsorption from Kidney. — ADDIS and SHEVKY, Am. J. Phys., 1917, 43,
363 (return of urea from kidney to blood). HENDERSON (V. E.), J. Phys.,
1905-6, 33, 175-
Saline, Diuresis. — CUSHNY, J. Phys., 1902, 28, 431. SOLLMANN, Am. J. Phys.,
1903, 9, 454. THOMPSON (W. H.), J. Phys., 1899-1900, 25, 487. WIN-
FIELD, ib., 1912, 45, 182 (osmotic pressure of blood and urine during diuresis
by Ringer' s fluid) . YAGI and KURODA, ib., 1915, 49, 162.
Tests of Renal Function. — MOSENTHAL, J. Am. Med. Ass., 1916, 67, 933;
Arch. Int. Med., 1915, 16, 733. PEPPER and AUSTIN, Am. J. Med. Sci.,
1913, 145, 254. ROWNTREE and GERAGHTY, J. Pharm. Exp. Ther., 1910,
1, 579J Arch. Int. Med., 1912, 9, 284 (phenolsulphonephthalein test).
Urea Excretion. — AMBARD, J. Phys. Path. Gen., 1910, 12, 209; AMBARD and
WEILL, ib., 1912, 14, 753 ; MCLEAN, J. Exp. Med., 1915, 22, 212 (numerical
laws of renal secretion of urea and NaCl). ADDIS and WATANABE, J. Biol.
Ch., 1916, 24, 203 ;i&., 27, 249 ;i&., 1917, 29, 381, 399 (rate of urea excretion) .
MENDEL and LEWIS, J. Biol. Ch., 1913, 16, 19, 37, 55 (rate of nitrogen
excretion as influenced by diet factors) .
Nephrectomy, etc. — HERTER and WAKEMAN, J. Exp. Med., 1899, 4, 177.
JACKSON and SAIKI, Arch. Int. Med., 1912, 9, 79. MACNIDER, J. Med.
Res., I9ii,24, 425 (ligationof one branch of renal artery). PILCHER (J. D.),
J. Biol. Ch., 1913, 14, 389 (N -excretion after ligation of branches of renal
arteries) .
Innervation of Kidney. — ASHER and PEARCE, Z. f. Biol., 1913, 63, 83 ; Zentralb.
f. Physiol., 1913, 27, 584 (secretory fibres). BURTON-OPITZ, Am. J. Phys.,
1916, 40, 437; J. Exp. Med., 1911, 13, 308. BURTON-OPITZ and LUCAS,
n8o BIBLIOGRAPHY
Pfliiger's Arch., 1909, 127, 143, 148. BRADFORD (J. R.), J. Phys., 1889.
10, 358 (vasomotors). JOST (W.), Z. f. Biol., 1914, 64, 441. DE SOUZA.
J. Phys., 1900, 26, 139-
lanervation of Bladder. — BARRINGTOX, Q. J. Exp. Phys., 1915, 9, 26.
ELLIOTT, J. Phys., 1905-6, 33, p. xxix. KNOWLTON, ib., 1911, 43, 91.
FAGGE, ib., 1902, 28, 304. LANGLEY, ib., 1901-2, 27, 252; ib., 1910, 40,
p. Ixii; ib., 1911, 43, 125. OTT, Zentralb. f. Physiol., 1895, 335 (centre).
STEWART (C. C.), Am. J. Phys., 1899, 2, 182; ib., 1900, 3, i. WADDELL,
J. Pharm. Exp. Ther., 1917, 10, 243 (drugs).
Excretion by Skin.— BENEDICT (F. G.), J. Biol. Ch., 1905, 1, 263 (nitrogenous
matter). SCHWENKENBECHER and SPITTA, Arch. Exp. Path. Pharm.,
1907, 56, 284 (NaCl and A"). TAYLOR (A. E.), J. Biol. Ch., 1911, 9, 21
(nitrogen, sulphur, phosphorus).
Sweat. — BIGGS, J. Med. Res., 1911, 24, 285; CAMERER, Z. f. Biol., 1901, 41,
271 (chemistry of sweat). O'CONNOR (J. M.), J. Phys., 1915, 49, 113 (in-
fluence of temperature on sweat secretion). WENDE and BUSCH, J. Am.
Med. Ass., 1909, 53, 207 (localized facial sweating following olfactory
stimuli) .
CHAPTER X.
METABOLISM, NUTRITION AND DIETETICS.
LUSK The Science of Nutrition. SCHRYVER, Bioch. J., 1906, 1, 123 (chemical
dynamics of animal nutrition) .
CARBOHYDRATE METABOLISM.
DAKIN and DUDLEY, J. Biol. Ch., 1913, 14, 555. JOHANNSON, Skand. Arch.
Phys., 1908, 21, i. WOODY ATT, Harvey Lecture, New York, 1915-16
(intermediate carbohydrate metabolism).
Dextrose. — DAVIS, Am. J. Phys., 1917, 43, 514 (intravenous injection).
MACLEOD, J. Lab. Clin. Med., 1917, 2, 112 (utilization). KLEINER, J. Exp.
Med., 1911, 14, 274 (excretion in stomach and intestine). JANNEY and
CSONKA, J. Biol. Ch., 1915, 22, 203 (glucose formation from body proteins).
MATHEWS (A. P.), J. Biol. Ch., 1909, 6, 3 (spontaneous oxidation of sugars).
LUSK, Am. J. Phys., 1908, 22, 174. RINGER, J. Biol. Ch., 1912, 12, 511;
STILES and LUSK, Am. J. Phys., 1903, 9, 380 (formation from amino-acids) .
MACLEOD and FULK, Am. J. Phys., 1917, 42, 193 (retention of dextrose by
liver and muscles) .
Glycogen. — BOTAZZI and D'ERRICO, Pfliiger's Arch., 1906, 115, 159 (physico-
chemical experiments). CREMER, Ergeb. d. Phys. (Bioch.), 1902, 803
(physiology of glycogen). HUBER and MACLEOD, Am. J. Phys., 1917, 42,
619; MACLEOD, Soc. Exp. Biol. Med., 1917, 14, 124; KAUFMANN, Compt.
Rend. Soc. Biol., 1895, 317 (glycogen in bloodvessels of liver). LANGSTEIN,
Ergeb. d. Phys. (Bioch. )( 1904, 453 (formation of carbohydrate from protein).
LUSK, Am. J. Phys., 1911, 27, 427 (cold baths and glycogen content).
MACLEOD and PEARCE, Am. J. Phys., 1911, 27, 341; ib., 1915, 38, 425
(sugar-retaining power and glycogen content of liver). PFLUGER (E.),
Pfliiger's Arch., 1902, 91, 119; ib., 1903, 98, i (monograph on glycogen);
ib., 1903, 93, 165 (directions for estimation) ; ib., 1904, 103, 169 (abbreviated
method). RUSK, Soc. Exp. Biol. Med., 1912, 12, 21 (comparison of
chemical and microchemical methods).
Glycogenesis. — EPSTEIN and BAEHR, J. Biol. Chem., 1916, 24, 17 (influence
of phlorhizin) . HATCHER and WOLF, ib., 1907, 3, 25 (formation of glycogen
in muscle). MACLEOD, Soc. Exp. Biol. Med., 1916, 13, 169 (influence of
alkali). McGuiGAN, J. Pharm. Exp. Ther., 1916, 8, 407 (influence of
atropin and pilocarpin). MCDANELL and UNDERBILL, J. Biol. Ch.,
1917, 29, 255 (relation of diet to glycogen content of liver). PFLtJGER (E.),
Pfliiger's Arch., 1907, 120, 253 (in starvation)
METABOLISM, NUTRITION AND DIETETICS ust
Glycogeiiolysis. — BANG, Bioch. Z., 1913, 49, 40, 81 ; MACLEOD and Run, Am. J.
Phys., 1908, 22, 397 (splanchnic stimulation). MACLEOD, ib., 22, 373
(glycogenolytic fibres in splanchnic?). MACLEOD and PEARCE, ib., 1911, 28,
403 (glycogenase). NEILSON and TERRY, ib., 1905, 14, 105. PAVY, J.
Phys., 1898, 22, 391. PATON (D. N.), J. Phys., 1899, 24, 36 (sugar
formation in liver). TAYLOR, J. Biol. Ch., 1908, 5, 315.
Blood-Sugar Content Methods. — FITZ (R.), Arch. Int. Med., 1914, 14, 133
(Bang and Bertrand methods compared). LEWIS and BENEDICT (S. R.),
J. Biol. Chem., 1915, 20, 61. MACLEOD, J. Lab. Clin. Med., 1916, 1, 445
(ffsttm/). McGuiGAN and Ross, J. Biol. Ch., 1917, 31, 533 (Benedict
and Bertrand methods compared). MORRIS, J. Lab. Clin. Med., 1916, 1,
208, 252. MYERS and BAILEY, J. Biol. Ch., 1916, 24, 147. PEARCE, ib.,
1915, 22, 525. SCOTT (E. L.), Am. J. Phys., 1914, 34, 271. SHAFFER,
J. Biol. Ch., 1914, 19, 285, 297.
Blood-Sugar Content. — EPSTEIN and ASCHNER, J. Biol. Ch., 1916, 25, 151.
(psychic and sensory stimuli). GRAHAM, J. Phys., 1916, 50, 285.
KRAMER and COFFIN, J. Biol. Ch., 1916, 25, 423 (psychic and sensory
stimuli). MACLEOD and WEDD, ib., 1914, 18, 447 (in hepatic vein).
McGuiGAN, Am. J. Phys., 1916, 39, 480. LEE and SCOTT, ib., 1917, 40,
486. MACLEOD, ib., 1909, 23, 278 (asphyxia). MACLEOD and PEARCE,
ib., 1915, 38, 415. MCDANELL and UNDERBILL, J. Biol. Ch., 1917, 29,
227, 233, 265 (alkali). RONA and MICHAELIS, Bioch. Z., 1908, 14, 476;
ib., 1909, 16, 60 (partition between corpuscles and plasma) Ross and
McGuiGAN, J. Biol. Ch., 1915, 22, 407 (ether anesthesia).
Glycolysis.— COHNHEIM, Z. Physiol. Ch., 1903, 39, 336; ib., 1904, 42, 401; ib.,
1905, 43, 547; ib., 1906, 47, 253; TUCKETT, J. Phys., 1910, 41, 89; CLAUS
and EMBDEN, Hofmeister's Beit., 1905, 5, 214; ib., 1906, 6, 343; LEVENE
and MEYER, J. Biol. Ch., 1911, 9, 97; ib., 1912, 11, 347; McGuiGAN, Am.
J. Phys., 1908, 21, 351 (muscle and pancreas). LEVENE and MEYER, J.
Biol. Ch., 1912, 11, 353 (action of tissues on glucose); ib., 1912, 11, 361
(leucocytes) .
Blood Glycolysis. — ARTHUS, Arch, de Phys., 1891, 425. LUPINE, J. Biol. Ch.,
1913, 16, 559. MACLEOD, J. Biol. Ch., 1913, 15, 497. MACLEOD and
PEARCE, Am. J. Phys., 1914, 33, 378. PAVY and SIAU, J. Phys., 1901-2,
27, 451. MACKENZIE (G. M.j, J. Exp. Med., 1915, 22, 757.
HYPERGLYC2EMIAS AND GLYCOSURIAS.
BROWN (O: H.), Am. J. Phys., 1904, 10, 378 (effect of Ca on glycosuria).
EDIE, Bioch. J., 1906, 1, 455 (excess of COZ in air). HENDERSON and
UNDERBILL, Am. J. Phys., 1911, 28, 275 (acapnia and glycosuria).
MACLEOD, Harvey Lecture, New York, February 14, 1914. McGuiGAN
and BROOKS, Am. J. Phys., 1907, 18, 256. PAVY and GODDEN, J. Phys.,
1911, 43, 199.
Salt Glycosuria. — BURNETT, J. Biol. Ch., 1908, 5, 351. FISCHER (M.),
Pflfiger's Arch., 1905, 106, So; 109, i; Univ. of Calif. Pub., Dec. 24,
1903 ; ib., Feb. 15, 1904. MCDANELL and UNDERBILL, J. Biol. Ch., 1917*
29, 273. UNDERBILL and KLEINER, ib., 1908, 4, 395.
Adrenalin Glycosuria.— BLUM, Pfliiger's Arch., 1902, 90, 617. HERTER and
WAKEMAN, Virchow's Arch., 169, 479. MCDANELL and UNDERBILL,
J. Biol. Ch., 1917, 29, 245. MACLEOD and PEARCE, Am. J. Phys. ,1912,
29, 419 (adrenals and sugar production by liver). PETERS and GEYELIN,
J. Biol. Ch., 1917, 31, 471. PATON (D. N.), J. Phys., 1903, 29, 286; ib.,
1905, 32, 59. POLLAK, Arch. Exp. Path. Pharm., 1909, 61, 149. UNDER-
BILL and CLOSSON, Am. J. Phys., 1906, 17, 42.. VOSBURGH and RICHARDS,
Am. J. Phys., 1903, 9, 35-
Relation of Adrenals to Experimental Hyperglycsemias. — KAHX. Pfliiger's
Arch., 1911, 140, 209; ib., 191^, 144, 251, 396; ib., 1912, 146, 576;
SCHWARZ, Pfliiger's Arch., 1910, 134, 259; WERTHEIMER and BATTEZ,
BIBLIOGRAPHY
Arch. Internal, de Phys., 1910, 9, 140, 363; NiSHl, Arch. Exp. Path.
Pharm., 1909, 61, 186 (puncture hyperglyctemia). STEWART and ROGOFF,
Am. J. Phys., 1917, 44, 543 (asphyxia and anesthesia).
Puncture G ycosuria. — BERNARD, Le9ons sur le systeme nerveux, t. 1, 440.
ECKHARD, Z. f. Biol., 1903, 44, 407.
Alimentary Hyperglyccemia and Glycosuria. — BAILEY, Soc. Exp. Biol. Med.,
1916, 13, 153. HOFMEISTER, Arch. Exp. Path. Pharm., 1889, 25, 240
(assimilation limits for sugars). MIURA, Z. f. Biol., 1898, 34, 281. TAYLOR
(A. E.) and HULTO'N, J. Biol. Ch., 1916, 25, 173; WILDER and SANSUM,
Arch. Int. Med., 1917, 19, 311 (sugar tolerance) .
Emotional Hyperglycsemia and Glycosuria. — CANNON, SHOHL and WRIGHT,
Am. J. Phys., 1911, 29, 280. FOLIN, DENIS and SMILLIE, J. Biol. Chem.,
1914, 17, 519. UNDERBILL, ib., 1917, 29, 279.
Ether Glycosuria. — KING, MOYLE and HAUPT, J. Exp. Med., 1912, 16, 178.
GRUBE, Pfluger's Arch., 1911, 138, 601. Ross and HAWK, Arch. Int.
Med., 1914, 14, 779. SEELIG, Arch. Exp. Path. Pharm., 1905, 52, 481.
Phlorhizin Diabetes. — CATHCART and TAYLOR, J. Phys., 1910, 41, 276.
LEVENE, ib., 1894, 17, 259. PAVY, BRODIE and SIAU, ib., 1903, 29, 467.
UNDERBILL, J. Biol. Ch., 1912, 13, 15 (mechanism of). DAKIN and
DUDLEY, J. Biol. Ch., 1914, 17, 451 (fate of alanin). LUSK, Am.
J. Med. Sci., 1917, 153, 40 (intermediary metabolism)', Am. J. Phys.,
1908, 22, 174 (sugar production from glutamic acid). MANDEL and LUSK,
Am. J. Phys., 1903, 10, 47 (respiration experiments). MCDERMOTT and
LUSK, ib., 1900, 3, 139 (phosphorus poisoning and phlorhizin). REILLY,
NOLAN and LUSK, ib., 1898, 1, 395. STILES and LUSK, ib., 1903, 10, 67
(action of phlorhizin). RINGER, J. Biol. Ch., 1914, 17, 107 (theory of
diabetes, acidosis). WOODYATT and SANSUM, J. Biol. Ch., 1915, 21, i
(narcotics in); ib., 1916, 24, 23 (determination of utilizable carbohydrates in
foods) .
Pancreatic Diabetes. — CARLSON and DRENNAN, Am. J. Phys., 1911, 28, 391;
CARLSON and GINSBURG, ib., 1915, 38, 217; CARLSON, ORR and JONES,
J. Biol. Ch., 1914, 17, 19 (influence of pregnancy). AUER and KLEINER,
Soc. Exp. Biol. Med., 1917, 14, 151 (coagulation of pancreas in situ).
EPSTEIN, J. Biol. Chem., 1916, 24, ROMANS, J. Med. Res., 1915, 33, i;
THIRD LOIX, Arch, de Phys., 1892, 24, 716 (diabetes after partial pancrea-
tectomy). EVANS (C. L.), J. Phys., 1912, 44, 461 (fate of secretin in).
HiDON, Arch. Internat. de Phys., 1911, 11, 195; ib., 1913, 13, 4; J. de
Phys. Path. Gen., 1912, 14, 907. MINKOWSKI, Pfluger's Arch., 1906,
111, 13; Arch. Exp. Path. Pharm., 1905, 53, 331. MURLIN and KRAMER,
J. Biol. Ch., 1916, 27, 517 (influence of alkali). MURLIN and SWEET,
ib., 1916, 28, 261 (influence of gastrectomy). UNDERBILL and FINE, ib.,
1911, 10, 271 (inhibition of pancreatic diabetes). SCOTT (E. L.), Am. J.
Phys., 1912, 29, 306 (influence of pancreatic extract). TUCKETT, J. Phys.,
1910, 41, 88. WOODYATT, J. Biol. .Chem., 1915, 20, 129.
Sugar Consumption in Diabetic Tissues.— CLARK (A. H.), J. Exp'. Med., 1917,
26, 721 (surviving heart and pancreas in sugar metabolism). CRUICKSBANK,
J. Phys., 1913, 47, i (glycogen in normal and diabetic animals). CRUICK-
SBANK and PATTERSON, ib., 1914, 47, 381; MACLEAN and SMEDLEY, ib.,
1912, 45, 470; PATTERSON and STARLING, ib., 1913, 47, 137; KNOWLTON
and STARLING, ib., 1912, 45, 146 (sugar consumption in diabetic heart).
HOAGLAND and MANSFIELD, J. Biol. Ch., 191 7. 31, 501 (muscle). MURLIN,
J. Biol. Ch., 1913, 15, 365 (respiratory exchange in depancreatized animal).
MACLEOD and PEARCE, Am. J. Phys., 1913, 32, 184 (normal and depan-
created eviscerated dogs). MILNE and PETERS, j. Med. Res., 1912, 26, 415
(glycolytic power of blood and tissues in diabetic organism). MYERS and
KILLIAN, Am. J. Phys., 1917, 42, 582 (diastatic activity ofbloodin diabetes).
STARLING, EVANS and LOVATT, J. Phys., 1914, 49, 67 (respiratory exchange
in diabetic heart). STEWART (H. A.), J. Exp. Med., 1910, 12, 59 (perfused
human heart). •
METABOLISM, NUTRITION AND DIETETICS 1183
Diabetes Mellitus. — ALLEN, Studies concerning Glycosuria and Diabetes,
Boston, 1913; Bost. Med. Surg. J., 1915, 173, 743; Am. J. Med. Sci., 1915,
150, 480; J. Am. Med. Ass., 1916, 66, 1525. CAMMIDGE, Lancet (London),
Oct. 6, 1917, 522. DAKIN and RANSOM, J. Biol. Ch., 1906, 2, 305;
FOSTER (N. B.), J. Biol. Ch., 1906, 2, 297; BAINBRIDGE and BEDDARD,
Bioch. J., 1906, 1, 429 (treatment with secretin). GREENWALD, J. Biol. Ch.,
1914, 18, 115 (glucose from citric acid}; ib., 1913, 16, 375 (glucose from
propionic acid}. BAER and BLUM, Arch. Exp. Path. Pharm., 1906, 55,
87; ib., 1907, 56, 92; ib., 1910, 62, 129 (decomposition of fatty acids in).
BENEDICT (F. G.) and JOSLIN, Carnegie Instit., Pub. 136, 1910
(metabolism in diabetes mellitus). BAINBRIDGE and BEDDARD, Bioch.
J., 1907, 2, 89 (diastatic ferments in). GEPHART, AUB, Du Bois and
LUSK, Arch. Int. Med., 1917, 19, 908 (metabolism). JANNEY, Arch. Int.
Med., 1916, 18, 584 (sugar from protein). JOSLIN, Arch. Int. Med., 1915,
16, 693 (carbohydrate utilization). MACLEOD (J. J. R.), Diabetes: Its
Pathological Physiology, London, 1913; J. Am. Med. Ass., 1910, 55, 2133
(experimental diabetes and diabetes mellitus). LUSK, Arch. Int. Med.,
i9°9, 3, i (metabolism in). MOORHOUSE, PATTERSON and STEPHENSON,
Bioch. J., 1915, 9, 171 (metabolism in experimental diabetes). Mossi:
J. de Phys. Path. Gen., 1901, 3, 792; 4, 128 (potatoes in). MURLIN and
GRAVER, J. Biol. Ch., 1916, 28, 289 (sodium carbonate action). VON
NOORDEN, Diabetes Mellitus, its Pathological Chemistry and Treatment.
WOODYATT, J. Am. Med. Ass., 1916, 66, 1910 (acidosis). MAGNUS-LEVY,
Arch. Exp. Path. Pharm., 1901, 45, 389 (acidosis). OPIE, J. Exp. Med.,
1900, 5, 527 (islets). CECIL, J. Exp. Med., 1909, 11, 266; RENNIE and
FRASER, Bioch. J., 1906, 2, 7 (islets). PAVY, Physiology of the Carbo-
hydrates; Lancet (London), Nov. 21, 28 and Dec. 12, 1908. MOORE,
EDIE and ABRAM, Bioch. J., 1906, 1, 446. RINGER, FRANKEL and JONES,
J. Biol. Ch., 1913, 14, 525; ib., 14, 539; 1914, 18, 81 (sugar formation in
diabetic organism) .
Diabetes Insipidus. — CHRISTIE and STEWART, Arch. Int. Med., 1917, 20, 10.
FITZ, ib., 1914, 14, 706. HERRICK (J. B.), ib., 1912, 10, i. MATTHEWS
(S. A.), ib., 1915, 15, 451.
Diabetic Coma. — BEDDARD, PEMBREY and SPRIGGS, J. Phys., 1904. 31,
p. xliv. ; ib., 1908, 37, p. xxxix. MAGNUS-LEVY, Arch. Exp. Path. Pharm.,
1899, 42, 149- POULTON, J. Phys., 1915, 50, i.
Acidosis.— FITZ and VAN SLYKE, J. Biol. Ch., 1917, 30, 389. VAN SLYKE,
ib., 1917, 30, 289. STLLLMAN and VAN SLYKE, J. Biol. Ch., 1917, 30, 457
(diabetes). WOOLLEY, J. Lab. Clin. Med., 1916, 1, 712 (r&sume). PALMER
and VAN SLYKE, J. Biol. Ch., 1917, 32, 499 (alkali retention and alhali
reserve) .
Acidosis and Respiration. — MACLEOD, J. Lab. Clin. Med., 1915, 1, 197 (methods).
KENNAWAY, PEMBREY and POULTON, J. Phys., 1913-14, 47, p. x.
PEABODY, Arch. Int. Med., 1914, 14, 236; ib., 1915, 16, 955. PETERS, Am.
J. Phys., 1917, 43, 113.
Acidosis, Experimental. — FITZ, ALSBERG and HENDERSON, Am. J. Phys.,
1907, 18, 113. HIRSCHFELDER, J. Am. Med. Ass., 1916, 67, 1891.
Acidosis in Nephritis. — BOSTOCK, Z. Physiol. Ch., 1913, 84, 468. GOTO, J.
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METABOLISM, NUTRITION AND DIETETICS 1185
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METABOLISM, NUTRITION AND DIETETICS 1187
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n88 BIBLIOGRAPHY
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METABOLISM, NUTRITION AND DIETETICS 1189
Phosphorus. — HART, McCoLLUM and FULLER, Am. J. Phys., 1909, 23, 246
(r$le of inorganic P in nutrition}. LUSK, Am. J. Phys., 1907, 19, 461
(influence on metabolism}. NASMITH and FIDLER, J. Phys., 1908, 37, 278.
PATON, DUNLOP, CRAWFORD and AITCHISON, J. Phys., 1899, 25, 212
(P metabolism}. SCOTT (F. H.), ib., 1906-7, 35, 119 (histo-chemical
methods for detection}. WEBER, Ergeb. d. Phys. (Bioch.), 1904, 284
(influence on metabolism}.
Iron. — ABDERHALDEN, Z. f. Biol., 1900, 39, 487; KUNKEL, Pfliiger's Arch.,
1895, 61, 595 (blood- formation} . DUBIN and PEARCE, J. Exp. Med.,
1917, 25, 675 (distribution in ancemia). MACALLUM (A. B.), J. Phys.,
1897, 22» 92 (micro-chemical reaction). STOCKMAN, J. Phys., 1895, 18,
484 (in food). STOCKMAN and GREIG, ib., 1897, 21, 55.
Metabolism, Quantitative Data. — BENEDICT and ROTH, J. Biol. Ch., 1915.,
20, 231 (vegetarians). BENEDICT and SMITH, ib., 1915, 20, 243 (athletes).
DUNLOP, J. Phys., 1896, 20, 82 (action of acids). GOODBODY, BARDSWELL
and CHAPMAN, J. Phys., 1902, 28, 257 (ordinary and forced diets). KRUM-
MACHER, Ergeb. d. Phys., 1906, 746. PFLUGER (E.), Pfliiger's Arch., 1899,
77, 425 (influence of quantity and kind of food) . RUBNER, Gesetze des
Energieverbrauchs. SPECK, Ergeb. d. Phys. (Bioch.), 1903, i. WEBER,
ib.-, 1904, 233 (influence of various substances on metabolism). ZUNTZ,
Pfliiger's Arch., 1903, 95, 192; Arch. f. Phys., 1895, 378 (work and
metabolism) .
Basal Metabolism. — AUB and Du Bois, Arch. Int. Med., 1917, 19, 840 (dwarfs
and legless men) ; ib., 1917, 19, 823 (old men). BENEDICT, EMMES, ROTH
and SMITH, J. Biol. Ch., 1914, 18, 139. BENEDICT and EMMES, ib., 1915,
20, 253 (men and women). GEPHART and Du Bois, Arch. Int. Med.,
1915, 15, 836 (effects of food). MEANS, J. Med. Res., 1915, 32, 121; Arch'.
Int. Med., 1916, 17, 704 (obesity).
DIETETICS.
BENEDICT (F. G.), Am. J. Phys., 1906, 16, 409. McCAY, The Protein Element
in Nutrition. CHITTENDEN, The Nutrition of Man, N. Y., 1907; Physio-
logical Economy in Nutrition, 1905. MACLEOD, J. Lab. Clin. Med.,
1917, 2, 743 (resume, economic readjustment of dietaries). MENDEL,
Changes in Food Supply and their Relation to Nutrition, Yale Univ.
Press, 1916. KNIGT, PRATT and LANGWORTHY, U.S. Dept. Agric.
Bull., 223, 1910 (dietary studies in public institutions). PEMBREY and
PARKER, J. Phys., 1907-8, 36, p. xlix (food of the soldier). Von (C.),
Physiologie des Stoffwechsels, 1881 . WILSON and RATHBUN, J . Am. Med.
Ass., 1916, 66, 1760 (dietary at N. Y. Municipal Sanitarium). SIVEN, Skand.
Arch. Phys., 1901, 11, 308; CASPARI, Arch. f. Phys., 1901, 323 (minimum
protein requirement). TAYLOR (A. E.), Univ. of Calif. Pub., July 30,
1904 (ash-free diet): RUBNER, Z. f. Biol., 1901, 42, 261 (energy value of
food of human beings). LITTLE and HARRIS, Bioch. J., 1907, 2, 230
(vegetarians) .
Inanition. — BENEDICT, N. Y. Med. J., Sept. n, 1907; Proc. Nat. Acad. Sci.,
1915, 1, 228. CATHCART and FAWCETT, J. Phys., 1907, 36, 27. GIVENS,
Soc. Exp. Biol. Med., 1917, 14, 149 (Ca and Mg metabolism}. GREENE,
Am. J. Phys., 1917, 42, 609 (changes in composition of muscle). HOOVER
and SOLLMANN, J. Exp. Med., 1897, 2, 405 (hypnosis). HOWE, MATTILL
and HAWK, J. Biol. Ch., 1912, 11, 103. KAUFMANN, Z. f. Biol., 1901,
41, 75. LEWIS (H. B.), J. Biol. Ch., 1916, 26, 61 (S and N elimination).
MEYERS, J. Med. Res., 1917, 36, 51 (morphological changes) . SnERWiNand
HAWK, J. Biol. Ch., 1912, 11, 169 (putrefaction in intestine). VOIT, Z. f.
Biol., 1901, 41, 167, 502; ib., 1905, 46, 167 (diminution in weight of organs).
WEBER, Ergeb. d. Phys. (Bioch.), 1902, 702. WOELFEL, J. Biol. Ch.,
1909, 6, 189 (transfer of protein).
Milk and the Suckling. — ABDERHALDEN, Z. Physiol. Ch., 1898-9, 26, 498
(ash of suckling znd ash of milk). CAMERER, Z. f. Biol., igoo, 39, 37
(physiology of suckling). LANGSTEIN, Ergeb. d. Phys., 1905, 851 (energy
U9o BIBLIOGRAPHY
balance of suckling). OPPENHEIMER, Z. f. Biol., 1901, 42, 147 (food
requirement and body surface of suckling). RUBNER and HEUBNER,
Z. f. Biol., 1898, 36, i (feeding of suckling). SIKES (A. W.), J. Phys.,
1906, 34, 464 (Ca and P of human milk).
Influence of Diet on Growth and Nutrition.— GARDNER and LAUDER, Proc.
Roy. Soc., 1914, B 87, 229; MUELLER, J. Biol. Ch., 1915. 21, 23 (cholesterol
and growth). MENDEL, Ergeb. d. Physiol., 1916, 102; Harvey Lecture,
New York, 1914-15. McCoLLUM, SIMMONDS and FITZ, J. Biol. Ch.,
1916, 27, 33 (fat-soluble A and water-soluble B and the growth-promoting
properties of milk). MENDEL and OSBORNE, J. Lab. Clin. Med., 1916,
1, 211 (resume). McCoLLUM and DAVIS, J. Biol. Ch., 1915, 23, 231
(essential factors in diet during growth). OSBORNE and MENDEL, J. Biol.
Ch., 1912, 12, 81 (growth on fat-free food) ; ib., 12, 473 (gliadin in nutrition) ;
ib., 13, 233 (maintenance experiments with isolated proteins); ib., 1914,
18, 95 (suspension of growth); ib., 1915, 20, 351 (comparative value of
certain proteins in growth, and the problem of the protein minimum) ; ib.,
1915, 23, 439 (resumption of growth) ; ib., 1916, 25, i (amino-acid minimum
for maintenance and growth). ROBERTSON (T. B.), J. Biol. Ch., 1916, 25,
635 (cholesterol and growth); ib.. 25, 647 (lecithin). WATSON (C.), Lancet
(Lond.). July 21, 1906, 145; Dec. 8, 1585 (excessive meat); Proc. Roy.
Soc. (Edin.), 1905-6, 26, 87 (varying diets). WATSON and HUNTER,
J. Phys., 1906,34, in.
Vitamines, Accessory Factors in Dietaries. — D^UMMOND and HALLIBURTON,
J. Phys., 1917, 51, 235 (nutritive value of margarine and butter substitutes).
FUNK (C.), Ergeb. d. Phys., 1913, 124; J. Biol. Ch., 1916, 25, 409 (exclusive
diet of oats) ; J. Phys., 1913, 46, 173 (chemistry of vitamine from yeast and
rice polishings); FUNK and MACALLUM, J. Biol. Ch., 1916, 27, 51 (lard
and butter-fat in growth); ib., 1915, 23, 413 (nature of growth-promoting
substances). HOPKINS (F. G.), J. Phys., 1912, 44, 425. MCCOLLUM,
SIMMONDS and FITZ, Am. J. Phys., 1916, 41, 361 (fat-soluble A). OSBORNE
and MENDEL, J. Biol. Ch., 1916, 24, 37 (butter-fat).
Polyneuritis, Beriberi. — FUNK and DOUGLAS, J. Phys., 1914, 47, 475 (relation
of beriberi to endocrine glands). McCoLLUM and KENNEDY, J. Biol. Ch.,
1916, 24, 491 ;ib., 1912, 45, 75. STEENBOCK, Am. J. Phys., 1917, 42, 610
(antineuritic substances from egg-yolk).
Pellagra. — CHITTENDEN and UNDERBILL, Am. J. Phys., 1917, 44, 13. McCoL-
LUM and SIMMONDS, J. Biol. Ch., 1917, 32, 181. VEDDER, Arch. Int.
Med., 1916, 18, 137-
Experimental Scurvy. — JACKSON (L.) and MOORE (J. J.), J. Infect. Dis., 1916,
19, 478. — MCCOLLUM and FITZ, J. Biol. Ch., 1917, 31, 229.
CHAPTER XI.
INTERNAL SECRETION.
BIEDL, Innere Sekretion. SCHJLFER, The Endocrine Organs, 1916. VINCENT
(S.), Internal secretion of the ductless glands, Ergeb. d. Phys., 1910,
451; ib., 1911, 218. KojiMA.(M.), Q. J. Exp. Phys., 1917, 11, 255
(relations between endocrine glands). MANN (F. C.), Am. J. Phys., 1916,
41, 1 73 (ductless glands and hibernation) .
PANCREAS.
Islets. — BENSLEY, Am. J. Anat., 1911-12, 12, 297. CECIL, J. Exp. Med., 1912,
16, i. HOMANS, Proc. Roy. Soc., 1913, B 86, 73; J. Med. Res., 1914.
30, 49. MILNE and PETERS, J. Med. Res., 1912, 26, 405 (atrophv of
pancreas after occlusion of duct). MACCALLUM (W. G.), Johns Hopkins
Hosp. Bull., Sep. 19, 1909. PRATT and MURPHY, J. Exp. Med., 1913, 17,
252 (transplantation of pancreas in spleen). VINCENT and THOMPSON,
J. Phys., 1906, 34, p. xxvii. D^WITT, J. Exp. Med., 1906. 8, 193.
INTERNAL SECRETION llgl
Internal Secretion of Pancreas. — DRENNAN, Am. J. Phys., 1911, 28, 396
(presence of, in blood). HEDON, Arch. Internat. de Phys., 1913, 13, 255
(pancreatic diabetes). (For additional references see Chapter X.)
SEXUAL ORGANS.
BAYLISS and STARLING, Ergeb. d. Phys., 1906, 684 (chemical correlations of
sexual organs). CARMICHAEL and MARSHALL, J. Phys., 1908, 36, 431
(compensatory hypertrophy of ovary). DIXON (W. E.), J. Phys., 1900-1,
26, 244 (action of orchitic extracts); ib., 1900, 25, 356; ROSENHEIM, ib.,
1917, 51, p- vi (spermine). HANES, J. Exp. Med., 1911, 13, 338; STEINACH,
Pfliiger's Arch., 1912, 144, 71 (interstitial cells of Leydig and internal
secretion of testicle). LIPSCHTJTZ, J. Phys., 1917, 51, 283. LOEWY.
Ergeb. d. Phys. (Bioch.), 1903, 130. MARSHALL and JOLLY, Q. J. Exp.
Phys., 1908, 1, 115 (heteroplastic transplantation of ovaries). OLIVER
(J.), J. Phys., 1912, 44, 355 (internal secretion of ovary). WHEELON and
SHIPLEY, Am. J. Phys., 1916, 39, 394 (effects of testicular transplants on
vasomotor irritability) .
Castration. — HENDERSON (J.), J. Phys., 1904, 31, 222 (castration and the
thymus). LIVINGSTON, Am. J. Phys., 1916, 40, 153 (effect on pituitary).
MARSHALL and HAMMOND, J. Phys., 1914, 48, 171 -(effect on horn growth) .
MCCRUDDEN, J. Biol. Ch., 1909, 7, 185 (effect on metabolism). MORGAN,
Soc. Exp. Biol. Med., 1915, 13, 31 (effect on feathers). SIMPSON and
MARSHALL, Q. J. Exp. Phys., 1908, 1, 257 (stimulation of nervi erigentes
after castration).
THYMUS.
GOODALL, J. Phys., 1905, 32, 191 (effect of castration) . HEWER, J. Phys., 1914,
47, 479 (effect of thymus feeding on reproductive organs). MARINE and
MANLEY, J. Lab. Clin. Med., 1917, 3, 48 (grafting ; relation of thymus to
sexual maturity). PATON, J. Phys., 1905, 32, 28 (thymectomy and growth
of sexual organs); ib., 1911, 42, 267 (relation of thymus and sexual organs
to growth). PATON and GOODALL, ib., 1904, 31, 49. PAPPENHEIMER,
J.Exp. Med., 1914, 19, 319;^-, 1914- 20, 477; PARK (E. A.), ib., 1917, 25,
129; VINCENT (S.), J. Phys., 1904, 30, p. xvi. (results of extirpation).
SEEMANN, Ergeb. d. Phys. (Bioch.), 1904, 45. VINCENT (S.), ib., 1911,
3°3-
PARATHYROID.
ARTHUS and SCHAFERMANN, J. Phys. Path. Gen., 1910, 177 (parathyroidectomy
and Ca salts in rabbit). CAMIS, J. Phys., 1909, 39, 73 ; MEIGHAM, J. Phys.,
1917, 51 (action of guanidin on muscle). COOKE (J. V.), J. Exp. Med.,
1910, 12, 45 (Ca and Mg excretion) ; ib., 1911, 13, 439 (N metabolism after
parathyroidectomy). HALSTED, Am. J. Med. Sci., 1907, 134, i; J. Exp.
Med., 1909, 11, 175; ib., 1912, 15, 205 (grafts). HOSKINS and WHEELON,
Am. J. Phys., 1914, 34, 263 (vasomotor irritability after parathyroidectomy).
JOSEPH and MELTZER, J. Pharm. Exp. Ther., 1911, 2, 361 (action of NaCl
after parathyroidectomy). KOCH (W. F.), J. Biol. Ch., 1912, 12, 313
(methyl guanidin in urine); ib., 1913, 15, 43 (toxic bases in urine after
parathyroidectomy); J. Lab. Clin. Med., 1916, 1, 299 (physiology of para-
thyroid). MARINE (D.), Soc. Exp. Biol. Med., 1914, 11, 117 (hyperplasia
in fowls). PATON ET AL., Q. J. Exp. Phys., 1917, 10. THOMPSON (F. D.).
Phil. Trans. Roy. Soc. (Lond.), 1910, B 201, 91 (thyroid and parathyroid
in vertebrates). WILSON, STEARNS, THORNTON and JANNEY, J. Biol. Ch.,
1915, 23, 123 (excretion of acids and ammonia after parathyroidectomy).
Parathyroid Tetany. — CARLSON, Am. J. Phys., 1912, 30, 309 (digestive tract in).
CARLSON and JACKSON, ib., 1911, 28, 133 (nature of tetany). GREENWALD,
J. Biol. Ch., 1916, 25, 223. HASKINS and GERSTENBERGER, J. Exp. Med.,
1911, 13, 314 (Ca metabolism in infantile tetany). KEETON, Am. J. Phys.,
1914, 33, 25 (secretion of gastric juice during the tetany). MACCALLUM
(W. G.), Med. News, Oct. 31, 1903 ; ib., 1905, 86, 625 (gastric and duodenal
dilatation in); Soc. Exp. Biol. Med., 1912, 9, 23 (seat of action in teiany).
II92 BIBLIOGRAPHY
MACCALLUM and VOEGTLIN, J. Exp. Med., 1909, 11, 118 (Ca in); J.
Pharm. Exp. Ther., 1911, 2, 421 (influence of various salts in). MAC-
CALLUM and VOGEL, J. Exp. Med., 1913, 18, 618. MACCALLVM. LAMBERT
and VOGEL, J. Exp. Med., 1914, 20, 149 (removal of Ca from the blood by
dialysis). MARINE (D.), ib., 1914, 19, 89. STOLAND, Am. J. Phys., 1914,
33, 283 (influence of the tetany on liver and pancreas). UNDERBILL and
BLATHERWICK, J. Biol. Ch., 1914, 19, 119 (influence of dextrose and Ca
lactate on blood-sugar and tetany).
THYROID.
ASHER, Pfluger's Arch., 1911, 139, 562 (history and methods). BAYLISS and
STARLING, Ergeb. d. Phys., 1906, 683 (chemical correlations of thyroid).
v. FURTH, ib., 1909, 9, 524; OSWALD, Pfluger's Arch., 1916, 164, 506
(thyroid and the circulation). VINCENT (S.), Ergeb. d. Phys., 1911, 233;
VINCENT and JOLLY, J. Phys., 1906, 34, 295 (functions of thyroid and
parathyroid).
Results of Thyroidectomy. — GLEY, Arch, de Phys., 1893, 467 (rabbit); ib.,
766 (dog). HALPENNY andGuNN, Q. J. Exp. Phys., 1911, 4, 237 (monkey).
HOSKINS and MORRIS, Soc. Exp. Biol., Med., 1917, 14, 74 (amphibia).
PALMER, Am. J. Phys., 1917, 42, 572 (pig). SIMPSON, Q. J. Exp. Phys.,
1913, 6, 119 (sheep). SMITH (J. L.), J. Phys., 1894, 16, 378 (heat regula-
tion). TATUM (A. L.), J. Exp. Med., 1913, 17, 636 (experimental cretinism).
Morphological Changes in Thyroid.— HALSTED (W. S.), Trans. Ass. Amer.
Physicians, 1913; Johns Hopkins Hosp. Rep., 1896, 1 (compensatory
hypertrophy). MARINE (D.), J. Exp. Med., 1914, 19, 376 (involution of
active hvperplasia in brook trout). MARINE and LENHART, Arch. Int.
Med., 1909, 4, 253, 440; MARINE and WILLIAMS, ib., 1908, 1, 349 (relation
iodine to thyroid structure). WATSON (C.), J. Phys., 1905, 32, p. xvi;
1906, 34, p. xxix; ib., 1907, 36, p. i (changes in, on meat diet).
Influence oi Thyroid on Metabolism. — CARLSON and JACOBSON, Am. J. Phys.,
1910, 25, 403; JACOBSON (C.), J. Biol. Ch., 1914, 17, 133 (blood- ammonia
after thyroidectomy). CRAMER and KRAUSE, Proc. Roy. Soc., 1913, B 86,
550 (carbohydrate metabolism and the thyroid). HUNTER (A.), Q. J. Exp.
Phys.. 1914, 8, 23 (thyro-parathyroidectomy and N metabolism in sheep).
KING (J. H.), J. Exp. Med., 1909, 11, 665; UNDERBILL and HILDITCH, Am.
J. Phys., 1909, 25, 66; KURIYAMA, Am. J. Phys., 1917, 43, 481 (carbo-
hydrate metabolism after thyroidectomy). McCuRDY (J.), J. Exp. Med.,
1909, 11, 798 (thyroidectomy and alimentary glycosuria).
Thyroid Feeding. — CARLSON, ROOKS and McKiE, Am. J. Phys., 1912. 30, 129
(attempts to produce hyperthyroidism). CRAMER and McCALL, Q. J. Exp.
Phys., 1917, 11, 59 (effect on gaseous metabolism). CUNNINGHAM (R. H.),
J. Exp. Med., 1898, 3, 147 (experimental thyroidism). GUDERNATSCH,
Am. J. Phys., 1915. 36, 370 (in rats). HEWITT (J. A.), Q. J. Exp. Phys.,
1914, 8, 113, 297 (influence of small amounts of thyroid and anterior lobe of
pituitary on metabolism). KURIYAMA, J. Biol. Ch., 1917, 33, 193 (storage
and mobilization of liver glycogen in).
Active Constituents of Thyroid. — BAUMANN, Z. f. Physiol. Ch., 1895-6, 21,
319 (thyroidin). CALDWELL, Am. J. Phys., 1912, 30, 42 (intravenous
injection of thyroid pressure liquid). CARLSON and WOELFEL, ib., 1910,
26, 32 (internal secretion of thyroid). FAWCETT, ROGERS. RAHE and BEEBE,
ib., 1914, 36, 113; FENCER, J. Biol. Ch., 1912, 11, 489; ib., 12, 55 (active
principle in thyroid and suprarenal before and after birth). GRAHAM (A.),
J. Exp. Med., 1916, 24, 345; LENHART, ib., 1915, 22, 739; ROGOFF and
MARINE, J. Pharm. Exp. Ther., 1916, 9, 57 (relation of effect on tadpoles
to amount of iodine). GUDERNATSCH, Arch. Entwick. Mech. d. Org.,
1912-13, 35, 457; Am. J. Anat., 1913, 15, 431 (effect on tadpoles). HUNT
and SEIDELL. J. Pharm. Exp. Ther., 1910, 2, 15 (thyreotropic iodine
compounds). HUNT (R.), J. Biol. Ch., 1905, 1, 33; LUSSKY (H. O.),
Am. J. Phys., 1912, 30, 63 (aceto-nitrile test). KENDALL, J. Biol. Ch.,
of i
ib.,
INTERNAL SECRETION
1915, 20, 501 (product of alkaline hydrolysis of thyroid). KOCH (F. C.),
J. Biol. Ch., 1914, 101 (nature of the iodine-containing complex in thyreo-
globulin). MARINE, ib., 1915, 22, 547 (in vivo absorption of KI by thyroid}.
MARINE and FEISS, J. Pharm. Exp. Ther., 1915, 7, 557 (absorption of KI
by perfused thyroid}. MARINE and ROGOFF, ib., 1916, 9, i (time required
for elaboration of the iodine-containing substance}. MORSE (M.), J. Biol.
Ch., 1914, 19, 421 (the principle accelerating involution in tadpoles).
OSWALD, Arch. Exp. Path. Pharm., 1909, 60, 115 (iodothyrin). PICK
and J?INELES, Z. Exp. Path. Ther., 1909, 7, 518. ROGOFF (J. M.), J.
Pharm. Exp. Ther., 1917, 10, 199 (tadpole method for standardization
of thyroid preparations.
Iodine Content of Thyroid. — ALDRICH, Am. J. Phys., 1912, 31, 125. FENCER,
J. Biol. Ch., 1913, 14, 397 (/ and P in feet al thyroids). HUNTER (A.),
ib., 1910, 7, 321 (estimation). HUNTER and SIMPSON, ib., 1915, 20, 119
(influence of diet of marine algce}. WATTS, Am. J. Phys., 1915, 38, 35^
(iodine content and bloodflow through thyroid).
Innervation of Thyroid.- — Secretory Nerves ? — ASHER and FLACK, Z. f. Biol.,
1911, 55, 83. BURGET, Am. J. Phys., 1917, 44, 492. CANNON, BINGER
and FITZ, ib., 1914, 36, 363. LEVY, ib., 1916, 41, 492. MANLEY and
MARINE, Soc. Exp. Biol. Med., 1915, 12, 202. MARINE, ROGOFF and
STEWART, Am. J. Phys., 1918, 45, 268. RAHE, ROGERS, FA WCETT and
BEEBE, ib., 1916, 34, 72.
Vasomotors of Thyroid. — FRANCOIS-FRANCK and HALLION, J. de Phys.
Path. Gen., 1908, 10, 442. STEWART (G N.), J. Phys., 1893, 15, 79-
Thyroid Grafts. — HESSELBERG (C.), J. Exp. Med., 1915, 21, 164 (auto- and
homaeo-grafts in guinea pig}. MANLEY and MARINE, J. Am. Med. Ass.,
1916, 67, 260.
ADRENALS.
Epinephrin (Adrenalin, Suprarenin).— ABEL (J. J.), Am. J. Phys., 1901, 5,
p. v; ib., 1903, 8, p. xxix; ALDRICH, ib., 1901, 5, 457; ib., 7, 359) v. FftRTH,
Hofmeister's Beit., 1902, 1, 243; TAKAMINE, J. Phys., 1901-2, 27, p. xxix
(isolation). ABEL and MACHT, J. Pharm. Exp. Ther., 1912, 3, 327, 334
(in toad's venom). EMBDEN and v. FURTH, Hofmeister's Beit., 1904, 4,
421. WEISS and HARRIS, Pfliiger's Arch., 1904, 103, 510 (destruction
in the body}. EWINS and LAIDLAW, J. Phys., 1910, 40, 275 (formation).
FUNK, J. Phys., 1911, 43, p. iv; GREER and WELLS, Arch. Int. Med.,
1909, 4, 291 (absent in hypernephroma) .
Action of Suprarenal Estract and Adrenalin. — AUER and GATES, J. Exp.
Med., 1917, 26, 201; JACKSON, J. Pharm. Exp. Ther., 1912, 4, 59 (on
lungs). BAINBRIDGE and TREVAN, J. Phys., 1917, 51, 460 (on liver).
BARBOUR and KLEINER, J. Pharm. Exp. Ther., 1915, 7, 541 (on vagus).
BARCROFT and PIPER, J. Phys., 1912, 44, 359 (on gaseous metabolism of
submaxillary} . BOTAZZI, D'ENRico and JAPELLI, Bioch. Z., 1908, 7, 431
(tin saliva and urine secretion). BROWN (E. D.), J. Pharm. Exp. Ther.,
1916, 8, 195. BURKET, Am. J. Phys., 1912, 30, 382 (on blood-pressure).
CANNON and GRAY, Am. J. Phys., 1914, 34, 232; GRABFIELD, Am. J.
Phys., 1916, 42, 46 (on coagulation). CANNON and NICE, ib., 1913, 32, 44;
GRUBER, ib., 1914, 33, 335; ib., 1917, 43, 530 (on muscular fatigue).
CANNON and LYMAN, ib., 1913, 17, 376; HOSKINS and MCCLURE, ib., 1912,
30, 192; MOORE and PURINTON, Pfliiger's Arch., 1900, 81, 483; Am. J.
Phys., 1900, 3, p. xv (depressor action of minimal doses). CUSHNY, J.
Phys., 1908, 37, 130; ib., 1909, 38, 259 (adrenalin isomers). EVANS and
OGAWA, ib., 1914, 47, 446 (on gaseous metabolism of heart}. EDMUNDS,
Am. J. Phys., 18, 129 (on blood-velocity}. ELLIOTT, J. Phys., 1905,
32, 401. FLEISHER and LOEB, J. Exp. Med., 1910, 12, 288 (on absorption).
GITHENS, J. Exp. Med., 1917, 25, 323. GOLLA and SYMES, J. Pharm.
Exp. Ther., 1913, 5, 87 (on bronchioles). GUNN, Cj. J. Exp. Phys., 1913,
7, 75 (on heart). GUNN and CHAVASSE, Proc. Roy. Soc., 1913, (on veins).
HAROLD, NIERENSTEIN and ROAF, J. Phys., 1910, 41, 308. HARTMANN
i iy4 BIBLIOGRAPHY
and FRASER, Am. J. Phys., 1917, 44, 353 (vasodilatation). HOSKINS,
GUNNING and BERRY, Am. J. Phys., 1916, 41, 513 (on circulation in limb).
HOSKINS and McCLURE, Arch. Int. Med., 1912, 10, 343 (blood-pressure).
HOSKINS, Am. J. Phys., 1915, 36, 423 (adrenals and sympathetic irrita-
bility). LAMSON, J. Pharm. Exp. Ther., 1916, 8, 167; LAMSON and
KEITH, ib., 247 (polycythcBmia). LANGLEY, J. Phys., 1901, 27f 237.
LEWANDOWSKY, Arch. f. Phys., 1899, 97 (smooth muscle, especially eye).
McGuiGAN and MOSTROM, J. Pharm. Exp. Ther., 1913, 4, 277; MAGNUS,
Pfluger's Arch., 1905, 108,48 (on intestine strips) . MANN and MCLACHLIN,
J. Pharm. Exp. Ther., 1917, 10, 251 (on pancreatic secretion). MEEK and
EYSTER, Am. J. Phys., 1915, 38, 62 (heart rate). MELTZER (S. J. and C.),
Am. J. Phys., 1903, 9, 252 (subcutaneous injection). MELTZER and AUER,
ib:, 1904, 11, 28, 40 (paradoxical pupil dilatation); ib., 11, 449 (frog's
pupil). NICE, ROCK and COURTRIGHT, ib., 1914, 34, 326 (on respiration).
OLIVER and SCHAFER, J. Phys., 1895, 18, 230. PARK, J. Exp. Med.,
1912, 16, 558 (bronchi). PILCHER and SOLLMANN, J. Pharm. Exp. Ther.,
1915. 6, 339 (on vasomotor centre). TAKAYASU, Q. J. Exp. Phys., 1916,
9, 347 (on skeletal muscle). VINCENT (S.), J. Phys., 1898, 22, in.
Determination of Epinephrin. — FOLIN, CANNON and DENIS, J. Biol. Ch.,
1912, 13, 477; SEIDELL, ib., 1913, 15, 197 (colorimetric) . ELLIOTT,
J. Phys., 1912, 44, 374 (pithed cat) ; ib., 1913, 46, p. xv.
Epinephrin Content of Adrenals. — ELLIOTT, J. Phys., 1912, 44, 374. McCoRD,
J. Biol. Ch., 1915, 23, 435 (foetus). RITCHIE and BRUCE, Q. J. Exp. Phys.,
1911, 4, 127 (effect of diphtheria toxine). SEIDELL and F.ENGER, U. S.
Hyg. Lab. Bull., 100, 1914, p. 57. STEWART and ROGOFF, J. Exp. Med.,
1916, 24, 709.
Epinephrin in Blood (and Tests for). — BARBOUR and PRINCE, J. Exp. Med.,
1915, 21, 330; BARBOUR, ib., 1912, 15, 403; JANEWAY and PARK, ib.,
1912, 16, 541; PARK, ib., 1912, 16, 532 (coronary artery test). DALE and
LAIDLAW, J. Phys., 1912, 45, I ; J. Pharm. Exp. Ther., 1912, 4, 75 (guinea
pig uterus test). JACKSON (D. E.), Am. J. Phys., 1909, 23, 226 (disappear-
ance after injection). Li WEN, Arch. Exp. Path. Pharm., 1904, 51, 415
(frog perfusion test). MEYER, Z. f. Biol., 1906, 48, 352; PARK and JANE-
WAY, Soc. Exp. Biol. Med., 1912, 9, 51 (artery ring test) . SCHULTZ (W. H.),
J. Pharm. Exp. Ther., 1909, 1, 291 (critique of tests). STEWART (G. N.),
J. Exp. Med., 1911, 14, 377 (biological tests — rabbit intestine and uterus
segments); ib., 1912, 15, 547 (absence of detectable epinephrin in venous
blood); ib., 1912, 16, 502 (comparison of plasma and serum on intestine
segments). STEWART and ROGOFF, J. Pharm. Exp. Ther., 1917, 9, 393
(partition between corpuscles and plasma). STEWART and ZUCKER, J.
Exp. Med., 1913, 17, 152, 174 (artery ring, frog perfusion, rabbit intestine
and uterus compared). TRENDELENBURG, Arch. Exp. Path. Pharm.,
1915.79, 154-
Epinephrin Secretion and Adrenal Innervation. — ASHER, Z. f. Biol., 1912, 58,
274; Pfluger's Arch., 1917, 166, 372. CANNON, AUB and BINGER, J.
Pharm. Exp. Ther., 1912, 3, 379 (nicotine). DREYER, Am. J. Phys., 1899,
3, 203. ELLIOTT, J. Phys., 1912, 44, 374; ib., 1913, 46, 285 (innervation) ;
ib., 1914, 49, 38 (some results of excision of adrenals). HOSKINS and
McPEEK, J. Am. Med. Ass., 1913, 60, 1777 (massage of adrenals). JOSEPH
and MELTZER, Am. J. Phys., 1912, 29, p. xxxiv (splanchnic stimulation).
O'CONNOR, Arch. Exp. Path. Pharm., 1912, 67, 195; ib., 68, 383.
STEWART, ROGOFF and GIBSON, J. Pharm. Exp. Ther., 1916, 8, -05
(splanchnic stimulation). STEWART and ROGOFF, ib.. 1916, 8, 479
(spontaneous liberation); ib., 1917, 10, 49 (asphyxia); J. Exp. Med., 1917,
26> 637 (effect of sensory stimulation); ib., 1917, 26, 613 (spinal centre for
epinephrin secretion); J. Pharm. Exp. Ther., 1917, 10, i (indispensa-
bility of epinephrin ?); Am. J. Phys., 1917, 44, 149 (relation of liberation
of epinephrin and adrenal blood-flow).
Adrenals and Metabolism.-^-EDMUNDs, J. Pharm. Exp. Ther., 1911, 2, 559;
MANN, Arch. Int. Med., 1915, 16, 781; PEMBERTON and SWEET, ib., 1912,
INTERNAL SECRETION 1195
10, 169 (relation to pancreas). LUSK and RICHE, ib., 1914, 13, 673;
RINGER, J. Exp. Med., 1910, 12, 105 (diabetes).
Disseminated Chromaffin Tissue. — BIEDL and WIESEL, Pfliiger's Arch., 1902,
91, 434. FULK and MACLEOD, Am. J. Phys., 1916, 40, 21. GASKELL
(J. F.), J. Phys., 1912, 44, 59 (distribution of medullary tissue in petro-
myzori) .
PITUITARY.
BLAIR BELL, Q. J. Exp. Phys., 1917, 11, 77 (experimental operations). GUSHING
(H.), The pituitary body and its disorders, Philadelphia, 1912; Johns
Hopkins Hosp. Bull., 1910, 21, 127 (experimental hypophysectomy) .
v. CYON, Pfliiger's Arch., 1900, 81, 267; J. Phys. Path. Gen., 1909, 11,
259. GOETSCH (E.), Q. J. Med., 1914, 7, 173 (review). HERRING (P. T.),
Q. J. Exp. Phys., 1908, 1, 121 (histology); ib., 1913, 6, 73 (comparative
anatomy and physiology) ; ib., 1914, 8, 267 (activity of pars intermedia and
pars nervosa)', ib., 1914, 8, 245 (origin of active material of posterior lobe).
PAULESCO, J. Phys. Path. Gen., 1907, 9, 441. SCHAFER, Proc. Roy.
Soc., 1909, B81, 442 (functions). SIMPSON and HUNTER, Q. J. Exp. Phys.,
1910, 8, 121 (relation between thyroid and pituitary). VINCENT (S.),
Ergeb. d. Phys., 1911, 309; Practitioner, Jan., 1915 (general review).
Influence on Growth and Metabolism. — ALDRICH, Am. J. Phys., 1912, 81,
94 (feeding to rats). BENEDICT and HOMANS, J. Med. Res., 1912, 25, 409
(metabolism after hypophysectomy). GUSHING and GOETSCH, J. Exp.
Med., 1915, 22, 25 (hibernation and the pituitary). MALCOLM (J.), J.
Phys., 1903, 30, 270. MAXWELL, Univ. of Calif. Pub., 1916, 5, 5; PEARL
(R.), J. Biol. Ch., 1916, 24, 123 (feeding -pituitary to fowl). MILLER and
LEWIS, Arch. Int. Med., 1912, 9, 601 (glycosuria after injection of extracts).
ROBERTSON (T. B.), J. Biol. Ch., 1916, 24, 397, 409; ROBERTSON and
DELPRAT, ib., 1917, 31, 567; SCHMIDT, J. Lab. Clin. Med., 1917, 2, 719
(tethelin). SCHAFER (E. A.), Q. J. Exp. Phys., 1912, 5, 203 (effect of
ovarian, pituitary, and thyroid tissue on growth of rats). WULZEN (R.),
Am. J. Phys., 1914, 34, 127 (growth in birds).
Action of Extracts. — ADDIS and BARNETT, Soc. Exp. Biol. Med., 1916, 14, 49
(on urea secretion by kidney). AUER and MELTZER, J. Pharm. Exp. Ther.,
1913, 4, 359 (pituitrin on depressor action of vagus). DALE, Bioch. J.,
1909, 4, 427. HAMBURGER (W. W.), Am. J. Phys., 1904, 11, 282; ib.,
1910, 26, 178 (anterior lobe). HOWELL, J. Exp. Med., 1898, 3, 245 (posterior
lobe). HOSKINS and MEANS, J. Pharm. Exp. Ther., 1913, 4,435 (pituitrin
diuresis). KING and STOLAND, Am. J. Phys., 1913, 32, 405 (action on
renal activity). NICE, ROCK and COURTRIGHT, Am. J. Phys., 1914, 35,
194 (on respiration). PATON and WATSON, J. Phys., 1912, 44, 413 (on
circulation of bird). PILCHER and SOLLMANN, J. Pharm. Exp. Ther.,
1915. 6, 405 (on vasomotor centre). SCHAFER and HERRING, Phil. Trans.
Roy. Soc. (Lond.), 1906, B 199, i (on kidney). WADDELL, Am. J. Phys.,
1916, 41, 529 (on frog's oesophagus).
Formation and Secretion (?) of Active Substance. — CARLSON and MARTIN,
Am. J. Phys., 1911, 29, 64 (question of infundibular secretion in cerebro-
spinal fluid). Cow (D.), J. Phys., 1915, 49, 367. FENGER, J. Biol. Ch.,
1915, 21, 283; ib., 1916, 25, 417 (composition and activity of- pituitary) .
KEETON and BECHT, Am. J. Phys., 1915, 29, 109 (stimulation of pituitary) .
McCoRD, J. Biol. Ch., 1915, 23, 435 (active substance in foetus). RABENS
and LIFSCHITZ, Am. J. Phys., 1914, 36, 47 (innervation) . WEED and
GUSHING, ib., 1915. 36, 77 (effect of pituitary extract on its secretion).
(For action of pituitary extract on milk secretion, see Chapter XIX.)
SPLEEN.
Splenectomy. — GOLDSCHMIDT and MARGOT, J. Exp. Med., 1915. 22, 319;
MENDEL and GIBSON, Am. J. Phys., 1907, 18, 201 (N metabolism in man).
RICHET, J. Phys. Path. Gen., 19x2, 14, 689; ib., 1913, 15, 579 (effects on
nutrition) .
II96 BIBLIOGRAPHY
Blood Changes after Splenectomy. — KARSNER and PEARCE, J. Exp. Med.,
1912, 16, 769. PEARCE, AUSTIN and MUSSER, ib., 1912, 16, 758 (h J93 (progression). BROOKS, Am. J. Phys., 1910, 27, 212 (effect of
lesions of dor sal roots). FORBES and GREGG, Am. J. Phys., 191 5, 39, 172
(strength of stimulus and reflex response) ', ib., 1915, 37, n8 (flexion reflex).
LANGLEY, J. Phys., 1900, 25, 364 (axon reflexes). MAYHEW, J. Exp. Med.,
1897, 2, 35 (time of reflex winking). MOORE and OERTEL, Am. J. Phys.,
1900, 3, 45 (reflexes after high section of cord). PAWLOW, Ergeb. d. Phys.,
1911, 345 (conditioned reflexes). PORTER (E. L.), Am. J. Phys., 1913,
31, 223 (reflex arc in asphyxia) ; ib., 1917, 43, 497 (variations in irritability
of reflex arc). SHERRINGTON and LASLETT, J. Phys., 1903, 29, 58 (inter-
connection of spinal segments). SHERRINGTON, Ergeb. d. Phys., 1905.
797 (co-ordination of reflexes, common path); J. Phys., 1904, 30, 37 (spinal
reflex and quality of cutaneous stimulus) ; ib., 1910, 40, 28 (flexion reflex,
crossed extension reflex); ib., 1906, 34, i; Q. J. Exp. Phys., 1910, 3, 213
(scratch reflex); Proc. Roy. Soc., 1907, B 79, 337; 1908, 80, 53; 1909,
81, 249; 1913, 86, 219 (reciprocal innervation of antagonistic muscles).
SIMPSON and HERRING, J. Phys., 1905, 32, 305 (cold narcosis and reflexes).
Knee-Jerk. — BOWDITCH and WARREN, J. Phys., 1890, 11, 25. FRANZ, Am.
J. Insanity, 1909, 65, 471. JOLLY, Q. J. Exp. Phys., 1911, 4, 67.
LOMBARD, J. Phys., 1889, 10, 122. SHERRINGTON, J. Phys., 1892, 13,
669 (posterior roots concerned). SNYDER, Am. J. Phys., 1910, 26, 474.
STEWART (P.), J. Phys., 1898, 22, 61. WALLER, ib., 1890, 11, 384.
Reversal of Reflexes. — BROWN (T. G.), Ergeb. d. Phys., 1913, 430. KNOWL-
TON and MOORE, Am. J. Phys., 1917, 44, 490 (reversal of reciprocal inhibi-
tion in earth-worm). SHERRINGTON and SOWTON, J. Phys., 1911, 42,
383 (chloroform and reversal); Proc. Roy. Soc., 1911, B 83, 435.
Inhibition in Nervous Reactions. — BROWN-S^QUARD, Arch, de Phys., 1889,
21, 751. HERING, Ergeb. d. Phys. (Bioph.), 1902, 503. FORBES (A.),
Q. J. Exp. Phys., 1912, 5, 149 (reflex inhibition). McDouGALL, Brain,
1903, 102 (2), p. 153. PAWLOW, Richet's Livre Jubilaire, 1912, 325.
YERKES, J. Comp. Neurol., 1904, 14, 124 (frog). SHERRINGTON, J. Phys.,
1907, 36, 185 (effect of strychnin); ib., 1913, 47, 196; Q. J. Exp. Phys.,
1908, 1, 67 (combination of excitation with inhibition).
Spinal Shock.— PIKE (F. H.), 1912, Am. J. Phys., 1912, 30, 436; Q. J. Exp.
Phys., 1913, 7, i. PORTER and MUHLBERG, Am. J. Phys., 1900, 4, 334
(inhibition after injury of cord?).
THE CENTRAL NERVOUS SYSTEM 1207
CEREBELLUM.
HERRICK (C. J.), J. Comp. Neurol., 1895, 5, 66 (histogenesis) ; ib., 1914, 24,
i (Necturus). LUCIANI, Ergeb. d. Phys. (Bioph.), 1904, 259. WILSON
and PIKE, Am. J. Phys., 1916, 41, 571 (lesions).
Localization. — BARONY, Wien. Klin. Woch., 1912, No. 52. BLACK, J. Lab.
Clin. Med., 1916, 1, 467 (resume). BRADLEY, J. Anat. and Phys., 1903,
37, 221 (fissures). LEWANDOWSKY, Arch. f. Phys., 1903, 129. MEYERS,
J. Am. Med. Ass., 1916, 67, 1745- MILLS and WEISENBURG, ib., 1914,
Nov. 21, 1813. VAN RYNBERK, Ergeb. d. Phys., 1908, 653.
Labyrinth and Equilibration. — ALEXANDER and KREIDL, Pfliiger's Arch.,
1902, 89, 475 (galvanic reaction in deaf mutes). BERITOFF, Q. J. Exp.
Phys., 1916, 9, 199 (labyrinthine reflexes in decerebrate preparation). BAR-
ANY, Z. f. Sinnesphysiol., 1906, 41 (2), 37. CYON, Pfliiger's Arch., 1900,
79, 211 ; Arch. f. Phys., 1897, 29 (vestibule and space perception) . EWALD
(J. R.), Pfluger's Arch., 1896, 521 (labyrinth and rigor). FISHER and
MULLER, Am. J. Phys., 1916, 41, 267 (cats). GOLLA, Proc. Roy. Soc.
Med., 1912, 5, 123. HENSEN, Pfliiger's Arch., 1899, 74, 22 (statocysts) .
KREIDL, Ergeb. d. Phys., 1906, 572 (vestibular apparatus). LEE (F. S.),
Am. J. Phys., 1898, 1, 128 (ear and lateral line in fishes). LYON (E. P.),
ib., 1900, 3, 86; 4, 77 (compensatory movements in fishes). MAXWELL,
(S. S.), ib., 1912, 29, 367. MILLS and JONES, J. Am. Med. Ass., 1916,
67, 1296. PARKER, Bull. U.S. Bur. Fisheries, 1909, 29, 45 (influence
of eyes, ears, etc., on movements o/ dog fish). PRINCE, Am. J. Phys., 1917,
42, 308 (kittens). WILSON and PIKE, Phil. Trans. Roy. Soc. (Lond.),
1912, B 203, 127; Arch. Int. Med., 1914, 14>-9ii. YERKES, Am. J. Phys.,
1907, 10, p. xviii. ZOTH, Pfluger's Arch., 1901, 86, 147 (ear of dancing
mouse) .
Postural Reflexes, Decerebrate Rigidity. — BROWN (T. G.), J. Phys., 1915, 49,
180 (plastic flexor tonus in monkey). COBB, BAILEY, and HOLTZ, Am. J.
Phys., 1917, 44, 239 (extensor rigidity). FROHLICH and SHERRINGTON,
J. Phys., 1903, 28, 14 (path of inhibitory impulses). MAGNUS and DE
KLEIJN, Pfliiger's Arch., 1913, 154, 163, 178; ib., 1915, 160,429 (postural
reflexes) ; ib., 1914,159, 218 (frog). MILLS (C. K.), J. Am. Med. Ass., 1916,
67, 1485 (problems of cerebral tone). ROAF, Q. J. Exp. Phys., 1913, 5, 31
(COZ output in decerebrate rigidity) . SHERRINGTON, Brain, 1915, 38, 191
(postural activity of muscle and nerve); Q. J. Exp. Phys., 1909, 2, 109.
J. Phys., 1898, 22, 319 (decerebrate rigidity and reflex co-ordination of
movements). VAN RIJNBERK, Arch. Neerland. de Phys., 1917, 1, 762
(muscular tonus and decerebrate rigidity). WEED, J. Phys., 1914, 48, 205.
Muscular Tonus. — BURNETT (T. C.), Soc. Exp. Biol. Med., 1915, 12, 177
(skeletal muscle). HOOKER, Am. J. Phys., 1912, 31, 47 (influence of
COZ and Oz on tone in bloodvessels and alimentary canal). LINGLE (D. J.),
Am. J. Phys., 1910, 26, 361 (plain muscle). MOTT and SHERRINGTON,
Proc. Roy. Soc., 1895, 57, 481 (influence of sensory nerves on movements
and nutrition of limbs). SHERRINGTON, J. Phys., 1894-5, 17, 211 (nerves
of muscles) .
Co-ordination of Movements. — BEEVOR, Ergeb. d. Phys., 1909, 326. Du Bois-
REYMOND (R.), Arch. f. Phys., Supp. Bd., 1900, 327; ib., 1902, Supp. Bd.,
27. HERING and SHERRINGTON, Pfluger's Arch., 1897, 68, 222 (inhibition
of voluntary muscles from cortex). MAGNUS, ib., 1909, 130, 219, 253 ;«!>.,
1910, 134, 545; SHERRINGTON, Proc. Roy. Soc., 1905, B 76, 160, 269
(reciprocal innervation) .
Basal Ganglia and Mid-Brain. — BROWN (T. G.), J. Phys., 1915, 49, 195, 208
(is progression learnt?). HERRICK (C. J.), J. Comp. Neurol., 1917, 28,
215 (mid-brain and thalamus of Necturus).
CEREBRUM.
BAGLIONI, Zentralb. f. Phys., 1901, 14, 97; MAXWELL (S.S.), J. Biol. Ch., 1907,
2, 183 (chemical stimulation). VON BECHTEREW, Arch. f. Phys., 1902,
264 (cortical secretory centres); ib,, 1905, 297 (urine and sweat centres);
1308 BIBLIOGRAPHY
ib., 1905, 525 (influence of cortex on sexual glands). BROWN (T. G.), Q. J.
Exp. Phys., 1910, 3, 139 (removal of cortex of one hemisphere); J. Phys.,
1914, 48, pp. xxx, xxxiii (post-central gyrus). CAMPBELL, Brit. Med. J.,
Feb. 6, 1904 (histological differentiation, summary). FLECHSIG, Lancet,
Oct. 19, 1901, 1027; Vogt., J. Phys. Path. Gen., 1900, 525 (myelination) .
FRANCOIS-FRANCK and PITRES, Arch, de Phys., 1885, 7, 149 (excitability).
FRANZ (S. I.), Psychol. Bull., 1911, 8, in ; ib., 1914, 11, 131 ; ib., 1916, 13,
149 (review and summary); J. Am. Med. Ass., 1906, 47, M64 (association
areas in monkeys). GOLTZ, Pfliiger's Arch., 1892, 51, 570; ib., 1899, 76,
411 (brain extirpations, monkey). HERRICK (C. J.), J. Animal Behav.,
1913, 3, 222 (origin of cerebral cortex). HOLMES (G.), J. Phys., 1901, 27,
i (histology of Goltz's ' brainless dog '). KARPLUS and KREIDL, Arch. f.
Phys., 1914, 155 (extirpation of hemispheres in monkeys). VON MONAKOW,
Ergeb. d. Phys. (Bioph.), 1902, 534; ib., 1904, 100 (localization). MOTT,
SCHUSTER and HALLIBURTON, Proc. Roy. Soc., 1910, B 82, 124 (cortical
lamination). ROLLETT, PflQger's Arch., 1900, 79, 303; 80, 638 (historical,
especially cm Gall's doctrines) .
Frontal Lobes. — BOLTON, Brain, 26, 215. FRANZ, Am. J. Phys., 1902, 8, i
(frontal lobes and sensori-motor habits); Arch, of Psychol., Mar., 1907,
No. 2 (functions) . HERRICK (C. J.), Science, 1910, 31, 7 (intelligence andits
organs). McDouGALL, Brain, 1901, 24, 577 (seat of psycho-physical
processes) .
Motor Areas. — VON BECHTEREW, Arch. f. Phys., 1899, Supp. Bd., 543 (man) ;
ib., 1900, 22 (sensory functions of motor area). BROWN and SHERRINGTON,
J. Phys., 1911, 48, 209 (baboon); ib., 1913, 46, p. xxii (recovery after
lesions). BROWN (T. G.), Q. J. Exp. Phys., 1915, 9, 82, 101, 117, 131
('facilitation ' in motor cortex in monkey). CUNNINGHAM, J. Phys., 1898,
22, 264 (opossum). FRANZ (S. I.), Psychol. Monographs, April, 1915.
GRUNBAUM and SHERRINGTON, Proc. Roy. Soc., 1901, B 69, 206; ib., 72,
152 (higher apes). HITZIG, Brit. Med. J., Dec. i, 1900. LEYTON and
SHERRINGTON, Q. J. Exp. Phys., 1917, 11, 135 (excitable cortex of chim-
panzee, orang-utan and gorilla). RUSSELL (J. R.), J. Phys., 1894-5, 17,
378 (eye-movements). SIMPSON and KING, Q. J. Exp. Phys., 1911, 4,
53 (sheep). SCHAFER, J. Phys., 1898-9, 23, 310 (sensory function).
ZIEHEN, Arch. f. Phys., 1899, 158 (relation between position and function
in motor region).
Sensory Localization in Cerebral Cortex. — DUSSER DE BARENNE (J. G.),
Q. J. Exp. Phys., 1916, 9, 355; Arch. Neerland. de Phys., 1916, 1, 15.
VON BECHTEREW, Arch. f. Phys., 1905, 53; 1912, 33; BLACK, J. Comp.
Neurol., 1913, 23, 193; HITZIG, Arch. f. Psychiat., 35, 385; SHARKEY,
Lancet, May 22, 1897, I399! VITZOU, Arch, de Phys., 1893, 678 (visual
centres). FRANZ, Am. J. Phys., 1911, 28, 308 (occipital lobes) . LARIONOW,
Pfliiger's Arch., 1899, 76, 608 (auditory centre, music). MUNK, Zentralb.
f. Phys., 9, 770 (tactile sensibility).
Fatigue of Nerve Cells (Centres). — CARLSON, Am. J. Phys., 1903, 2, 341
(retina). DOLLEY, ib., 1909, 25, 151 ; J. Med. Res., 1909, 21,95; *'&-. I9IIt
25, 285 (Purkinje cells); ib., 1913, 29, 65. EVE, J. Phys., 1896, 20, 334.
HODGE, J. Phys., 1894-5, 17, 129. KOCHER, J. Am. Med. Ass., 1916,
67, 278. LEGENDRE and PiisRON, J. Phys. Path. Gen., 1911, 13, 519.
LEVY, J. Phys., 1900-1, 26, 210; ib., 1903, 28, i. PUGNET, J. Phys. Path.
Gen., 1901, 3, 183.
Sleep. — BRUSH and FAYERWEATHER, Am. J. Phys., 1901, 5, 199 (changes in
blood- pressure). BRODMANN, J. Psych. Neurol., 1, 10; Zentralb. f.
Physiol., 16, 310. GODDARD, J. Comp. Neurol., 1898, 8, 245 (movements
of nerve cells). HOWELL, J. Exp. Med., 1897, 2, 3^13 (plethysmograms in).
WALDEN, Am. J. Phys., 1900, 4, 124 (hypnotic slafp).
Cerebral Circulation.- — BROWN (E. D.), J. Pharm. Exg. Ther.VgiG, 8, 185.
CANNON (W. B.), Am. J. Phys., 1902, 6, 91 (cerebral j)ressuieg afar trauma),
GRtiNBAUM and SHERRINGTON, Brain, 25, 270 (apes). H?LL fL.), Phil.
Trans. Roy. Soc., 1900, B 193, 69 (ligation of cer&ral arteries). MOTT
THE CENTRAL NERVOUS SYSTEM 1209
and HILL, J. Phys., 1898-9, 23, p. xix; ib., 1906, 34, p. iv (histological
changes after cerebral anemia). HOWELL, Am. J. Phys., 1898, 1, 57
(effect of high arterial pressure). KRAMER, J. Exp. Med., 1912, 15, 348
(function of circle of Willis). JENSEN, Pfliiger's Arch., 1905, 107, 81.
Resuscitation of Central Nervous System. — PIKE, GUTHRIE and STEWART,
J. Exp. Med., 1908, 10, 490; Am. J. Phys., 1908, 21, 359 (reflex excita-
bility after cerebral anamia). STEWART, GUTHRIE, BURNS and PIKE,
J. Exp. Med., 1906, 8, 289.
Chemistry of Central Nervous System. — GIES, J. Biol. Ch., 1907, 2, 159
(cerebron). HATAI, Am. J. Phys., 1904, 12, 116 (effect of partial starvation).
KOCH (W.), Z.f. Physiol. Ch., 1902, 36, 134 (lecithin, kephalinandcerebrin).
KOCH (W. and M. L.), J. Biol. Ch., 1913, 15, 423 (rat); ib., 1917, 31, 395-
KOCH and MANN, J. Phys., 1908, 36, p. xxxvi (human brains). LEVENE,
J. Biol. Ch., 1912, 13, 463 (sulphatide) . LEVENE and WEST, J. Biol.
Ch., 1917, 31, 635, 649; LEVENE, ib., 1913, 15, 359 (cerebrosides) ; ib., 1916,
24, 41 (kephalin). ROSENHEIM, Bioch. J., 1913, 7, 604; ib., 1914, 8, no
(galactosides). TEBB, J. Phys., 1906, 34, 106 (cholesterol).
Cerebrospinal Fluid. — BLUMENTHAL, Ergeb. d. Phys. (Bioch.), 1902, 285.
CARTER (W. S.), Arch. Int. Med., 1912, 10, 425 (intraspinal injection of
Ringer's solution). DIXON and HALLIBURTON, J. Phys., 1913, 47, 215
(secretion) ; ib., 1914, 48, 128, 317 (pressure) ; ib., 1916, 50, TQ8 (circulation).
FRAziERand PEET, Am. J.Phys., 1914, 35, 268 (formation and circulation) ;
ib., 1915, 36, 464. KRAMER (S. P.), New York Med. J., Mar. 16, 1912
(circulation). SPINA, Pfliiger's Arch., 1899, 76, 204; ib., 1900, 80, 370;
ib., 1901, 83, 120, 415. THOMSON, HALL and HALLIBURTON, Proc. Roy.
Soc., B 64, 343 (man). WEED and GUSHING, Am. J. Phys., 1915, 36, 77.
Chemistry of Cerebrospinal Fluid. — CARLSON and MARTIN, Am. J. Phys., 1911,
29, 64 (pituitary secretion in?). FELTON, HUSSEY and BAYNE-JONES,
Arch. Int. Med., 1917, 19, 1085. FINE and MYERS, Soc. Exp. Biol. Med.,
1916, 13, 126 (non-protein N"). HALVERSON and BERGEIM, J. Biol. Ch.,
1917, 29, 337 (calcium). HURWITZ and TRANTER, Arch. Int. Med.,
1916, 17, 828. KAHN and NEAL, Soc. Exp. Biol. Med., 1916, 14, 26.
KRAMER (S. P.), Brain, 1911, 34, 39. KRAUSE and CORNEILLE, J. Lab.
Clin. Med., 1916, 1, 685; NAWRATSKI, Arch. f. Phys., 1897, T56 (sugar in).
MYERS, J. Biol. Ch., 1909, 6, 115; ROSENBLOOM, Arch. Int. Med., 1914,
14, 536 (potassium). WESTON, J. Med. Res., 1917, 35, 367 (reaction).
WOODS, Arch. Int. Med., 1915, 16, 577 (nitrogen).
CHAPTER XVII.
THE AUTONOMIC NERVOUS SYSTEM.
Autonomic System.— ANDERSON (H. K.), J. Phys., 1902, 28, 499 (regeneration
of sympathetic). BROWN and SHERRINGTON, Q. J. Exp. Phys., 1911, 4,
193 (pilomotor system). BURTON-OPITZ (R.), Am. J. Phys., 1916, 41,
103 ; ib., 1917, 42, 498 (depressor function of thoracic sympathetic). DASTRE
and MORAT, Arch.de Phys. ,1882, 33j(vasodilatator sin cervical sympathetic).
EDWARDS (D. J.), Am. J .Phys., 1914, 33, 220 (sympathetic nervous
system in the turtle). GASKELL, J. Phys., 1886, 7, i. HERRING (P. T.),
J. Phys., 1903, 29, 282 (spinal origin of cervical sympathetic). LANGLEY,
Ergeb. d. Phys. (Bioph.), 1903, 818 (autonomic system of vertebrates).
LANGLEY, J. Phys., 1894-5, 17, 296 (secretory and vasomotor fibres of cat's
foot) ; ib., 1896, 20, 55 (medullated fibres of the sympathetic system}. LANG-
LEY, J. Phjps., 1899-1900, 25, 468; ib., 1904, 31, 244 (commissural fibres in
-. LANGLEY and ANDERSON, J. Phys., 1895-6, 19, 71,
ation of pelvic and adjoining viscera); ib., 17, 177 (hypogastric
and ORBELI, J. Phys., 1910, 41, 450; ib., 1911, 42,
ttic-and sacral autonomic system of amphibia). MELTZER
. J. Phys., 1903, 9, 57 (vasomotor nerves of rabbit's ear).
12 io BIBLIOGRAPHY
CHAPTER XVIII.
THE SENSES.
HELMHOLTZ, Physiologische Optik. HELMHOLTZ, Tonempfindungen (trans-
lated by Ellis). MULLER, Ergeb. d. Phys. (Bioch.), 1903, 267 (psycho-
physical methods) .
VISION.
Eye Liquids. — HENDERSON (E. E.) and STARLING, J. Phys., 1904, 31, 305;
Proc. Roy. Soc., 1906, B 77, 294 (intraocular pressure and secretion).
HILL and FLACK, ib., 1912, B 85, 439 (secretion of aqueous). WESSELY,
Ergeb. d. Phys., 1905, 565.
Accommodation. — BARRETT, J. Phys., 1885, 6, 46. BEER, Pfliiger's Arch.,
1894, 58, 523; ib., 1897, 67, 541; 69, 507; Science, Nov. 18, 1904. EIN-
THOVEN, Ergeb. d. Phys. (Bioph.),. 1902, 680. HESS, Arch. f. Ophthal.,
42, 288 (velocity of accommodation). SCHOEN, Pfliiger's Arch., 1895, 59,
427. SNELLEN, Ergeb. d. Phys. (Bioph.), 1904, 339 (skiascopy). STUART
(T. P. ANDERSON), J. Phys., 1904, 31, 38. TSCHERNING, Arch, de Phys.,
1892, 138; ib., 1894, 4°; ^95- I58, 181; J. Phys. Path. Gen., 1899, 312.
Iris. — ANDERSON (H. K ), J. Phys., 1906, 33, 156, 414; ib., 1904, 30, 15, 290;
MELTZER and AUER, Am. J. Phys., 1904, 11, 28 (paradoxical dilatation
of pupil). COBB (P.), Am. J. Phys., 1914, 36, 335 (pupil diameter and
visual acuity). GUTHRIE and RYAN, Science, 1910, 31, 395 (effect of
asphyxia on pupil). GRUNERT, ZenLralb. f. Phys., 1899, 12, 406.
ScftiFER, Cj. J. Exp. Phys., 1908, 2, 287 (dilator pupillee in man).
Eye Movements and Innervation. — DODGE, Am. J. Phys., 1903, 8, 307.
HOFMANN, Ergeb. d. Phys. (Bioph.), 1903, 799; 1906, 599. SHERRINGTON,
J. Phys., 1896, 17, 27; ib., 1916, 50, p. xlvi (apparatus to illustrate
Listing-Danders law). ZOTH, Nagel's Handbuch der Physiologic.
Retina. — DITTLER, Pfluger's Arch., 1907, 117, 295 (contraction of cones).
FERREE nd RAND, Am. J. Phys., 1912, 29, 398; HANSELL, Philadelphia
Med. J., Oct., 1899; HAYCRAFT (J. B.), J. Phys., 1910, 40, 492 (blind spot).
LAURENS and WILLIAMS, Soc. Exp. Biol. Med., 1916, 13, 183 (movements
of retinal elements). TRENDELENBURG, Ergeb. d. Phys., 1911, i.
TSCHERMAK, Ergeb. d. Phys. (Bioph.), 1902, 695 (functions of rods and
cones) .
Colour Vision. — CALKINS, Arch. f. Phys., 1902, Supp. Bd., 244. EDRIDGE-
GREEN, J. Phys., 1915, 49, 265. EXNER, Zentralb. f. Phys., 1903, 17,
24 (Young-Helmholtz system). FRANKLIN (Mrs. C. L.), Z. f. Psych, u.
Phys. d. Sinn., 1892, 4; Psychol. Review, 1894, 1896, 1899. HARTRIDGE,
J. Phys., 1912, 45, p. xxix (yellow sensation). HERING (E.), Pfluger's
Arch., 1888, 42, 33°-
Contrast — After-images. — EDRIDGE-GREEN, J. Phys., 1912, 43, p. xxviii;
45, p. xix (simultaneous colour contrast); ib., 1913, 46, 180; 47, p. vi
(after-images). HARTRIDGE, J. Phys., 1915, 50, 47 (contrast). TSCHER-
MAK, Ergeb. d. Phys. (Bioph.), 1903, 726 (contrast and irradiation).
Colour-Blindness. — COLLIN and NAGEL, Z. f. Sinnesphysiol., 1906, 41, 74
(violet blindness). EDRIDGE-GREEN, Nature, Feb. io, 1910, p. 429 (tests) ;
J. Phys., 1912/43, P- xxxiv; Colour Blindness and Colour Perception,
London. GRUNERT, Graefe's Arch. f. Ophthal., 56, 132. HESS and
HERING, Pfluger's Arch., 1898, 71, 105. HESS, Z. f. Psych, u. Physiol.
d. Sinn., 29, 99. VON KRIES, ib., 32, 113. PEDDIE, Trans. Roy. Soc.
(Edin.), 1896, 501. POLE (W.), Contemporary Review, May, 1882.
SCHENCK, Pfluger's Arch., 1907, 118, 129.
Intermittent Stimulation of Retina. — CHARPENTIER, Arch, de Phys., 1896,
677 (retinal oscillations). SCHENCK (F.), Pfluger's Arch., 1906, 112, 292.
SHERRINGTON, J. Phys., 1897, 21, 33 (reciprocal action in retina).
STEWART (G. N.), Trans. Roy. Soc. (Edin.), July 16, 1888, 445 (colour
THE SENSES 12 1 1
phenomena afterwards described for Benham's top). BIDWELL, Proc. Roy.
Soc. (Lond.), June 7, 1894; Nature, Sept. 6, 1894, 466; PERCIVAL, Trans.
Ophthal. Soc., 1909, 29, 119.
Talbot's Law.— BURCH, J. Phys., 1898-9, 23, p. vii (and flicker). GR^NBAUM
(O. F. F.), J. Phys., 1898, 22, 433. MARBE, Pfliiger's Arch., 1903, 97,
335. PARKER and PATTEN, Am. J. Phys., 1912, 31, 22. STEWART (G. N.),
Trans. Roy. Soc. (Edin.), July 16, 1888, 441 (for very short stimuli).
Heliotropism (Phototropism).— DAVENPORT and CANNON, J. Phys., 1897,21,
22. HOLT and LEE, Am. J. Phys., 1900, 4, 460. LOEB and WASTENEYS,
J.Exp. Zool., 1915, 19, 23; 20, 217 ;ib., 1917, 22, 187.
HEARING, SMELL, TASTE.
Hearing. — BERNOUILLI, Pfluger's Arch., 1910, 134, 633. EWALD (J. R.), ib.,
1895, 59, 258; ib., 1903, 93, 485; WUNDT, ib., 1895, 61, 339 (labyrinth and
hearing). EWALD, ib., 1899, 76, 147 (sound picture theory). HENSEN,
Ergeb. d. Phys. (Bioph.), 1902,847. KOLMAR, 26. ,1911, 372 (endapparatus
of eighth nerve and its significance). E. TER KUILE, Pfluger's Arch., 1900,
79, 146, 484; MEYER (M.), ib., 1900, 81, 61 (theory of hearing). McKEN-
DRICK, Nature, June 15, 1899, 163 (perception of musical tone) . PARKER
(G. H.), U. S. Fish Commission Bull., 1903, 45; Am. Naturalist, 37, 185
(hearing in fi shes) . WITTEMAACK, Pfluger's Arch., 1907, 120, 249 (support
of Helmholtz's resonance theory). ZWAARDEMAKER, Arch. f. Phys., 1905,
Supp. Bd., 124 (sound-pressure in Corti's organ as the stimulus).
Smell and Taste. — GUSHING (H.), Am. J. Phys., 1903, 8, p. xxvii; GOWERS,
T. Phys., 1903, 28, 300; HARRIS (W.), J_. Am. Med. Ass., 1914, 63, 1725
(course of taste fibres). PARKER and STABLER, Am. J. Phys., 1913, 32,
230 (distinctions between smell and taste). ZWAARDEMAKER, Ergeb. d.
Phys. (Bioph.), 1902, 896 (smell); ib., 1903, 699 (taste) ; Arch. f. Phys.,
1907, Suppl. Bd., 59; ib., 1908, 51.
COMMON SENSIBILITY.
Cutaneous Sensations. — BARKER (L. F.), J. Exp. Med., 1896, 1, i (localized
sensory paralysis). BORING, Q. J. Exp. Phys., 1916, 10, i ; HEAD, RIVERS
and SHERREN, Brain, 110, 100; HEAD and SHERREN, Brain, 110, 116;
TROTTER and DAVIES, J. Phys., 1909, 38, 134; (Brodmann's) J. f. Psych.
Neurol., 1913, 20, 102 (section of cutaneous nerves in man). Buck (M.),
Arch. f. Phys., 1901, i. LOMBARD (W. P.), Am. J. Phys., 1913, 31, p. xv;
STANLEY HALL and ALBIN, Am. J. Phys., 1897, 9, 10 (tickle-sense).
CARR, Psychol. Review, 1916, 23, 252 (Head's theory). ELO and NICOLAI,
Skand. Arch. Phys., 1910, 24, 226 (warmth sense). FRANZ and RUEDIGER,
Am. J. Phys., 1910, 27, 45 (effect of local anesthetics) . FRANZ, J. Comp.
Neurol. Psychol., 1909, 19, 107 (pressure sense). VON FREY, Z. f. Biol.,
1913-14, 63, 207, 335; J. Am. Med. Ass., 1906, 47, 645; Ergeb. d. Phys.,
1913. 96; MAY (P.), ib., ' 1909, 657 (cutaneous sensations). NAGEL,
Handbuch d. Physiol., 3, 703 (tickling and itching). YERKES (R. M.),
Pfluger's Arch., 1905, 107, 207 (facilitation and inhibition of tactile
stimuli in the frog) .
Sensibility of Internal Organs. — HERTZ, The Sensibility of the Alimentary
Canal, 1911. KAST and MELTZER, Med. Rec., Dec. 29, 1906.
Muscular Sense. — VON Frey, Z. f. Biol., 1914, 63, 129; 64, 203. LASHLEY,
Am. J. Phys., 1917, 43, 169 (accuracy of movement in absence of excita-
tion from moving organ).
Localization of Sensations. — BROWN (T. G.) and STEWART (R. M.), Brain,
1916, 39, 348. LANGSTROTH, Arch. Int. Med., 1915, 16, 149 (referred pain,
Head's zones of hyper algesia) .
Hunger and Appetite.- — CANNON and WASHBURN, Am. J. Phys., 1911, 29,
441; CARLSON (A. J.), Am. J. Phys., 1912-13, 31, 151, 175, 212; ib., 1913,
32, 369; ib., 1914, 33, 95; 34, 155 (nervous control of hunger contractions).
CARLSON, Control of Hunger in Health and Disease, Chicago, 1916.
12 12 BIBL1CGRAPHY
CARLSON and LEWIS, Am. J. Phys., 1914, 34, 149 (influence of smoking}.
CARLSON, ORR and MCGRATH, ib., 33, U9- GINSBURG, TUMPOWSKI and
CARLSON, J. Am. Med. Ass., 1915, 64, 1822 (hunger in infants after feeding) .
LUCKHARDT, Am. J. Fhys., 1915, 39, 335 (dreaming). LUCKHARDT and
CARLSON, ib., 1914, 36, 37 (chemical control). MEYER and CARLSON, ib.,
1917, 44, 222 (in fever). PATTERSON, ib., 1915, 37, 316; 1916, 42, 56.
ROGERS and HARDT, ib., 1914, 38, 274.
CHAPTER XIX.
REPRODUCTION.
BURIAN, Ergeb. d. Phys. (Bioch.), 1904, 84; ib., 1906, 768 (chemistry of sperma-
tozoa). MARSHALL (F. H. A.), Physiology of Reproduction, London, 1910.
Ovary.— CARMICHAEL and MARSHALL, Proc. Roy. Soc., 1907, B 79, 387
(correlation of ovary and uterus). GUTHRIE (C. C.), J. Exp. Zool., 1908,
5. 563 (transplantation of ovaries in chickens) ; Science, Nov., 1909 (guinea-
pig graft hybrids); ib., 1911, 33, 816 (influence on offspring of engrafted
ovarian tissue). LOEB (L.), Soc. Exp. Biol. Med., 1916, 13, 162 (cyclic
changes); J. Am. Med. Ass., 1917, 69, 236 (relation of ovary to uterus and
mammary gland). ROSENBLOOM, J. Biol. Ch., 1912, 13, 511 (lipins of
ovary and corpus luteum) .
Corpus Luteum. — ANCEL, J. de Phys. Path. Gen., 1911, 13, 31. BOUIN and
ANCEL, ib., 1910, 12, 16. ITAGAKI, Q. J. Exp. Phys., 1917, 11, i (influence
of extracts on plain muscle). LOEB (L.), J. Am. Med. Ass., 1906, Feb. 10,
1906; Anat. Record, 1908, 2, 240. MARSHALL, Q. J. Exp. Micros. Sc.,
1905, 49, 189 (development, review). NOVAK, J. Am. Med. Ass., 1916,
67, 1285. OTT and SCOTT, Soc. Biol. Exp. Med., 1912, 9, 64 (extracts) ; ib.,
1914, 12, 47 (action on mammary glands). PEARL and SURFACE. J. Biol.
Ch., 1914, 19, 263 (effect on ovulation).
Uterus. — BARRY (D. T.), J. Phys., 1915, 50, 259 (uterus contractions and
ovarian extract). CUSHNY, J. Phys., 1906, 35, i (movements). BARBOUR
and COPENHAVER, Soc. Exp. Biol. Med., 1916, 13, 159 (cerebral control
of uterus ?). KURDINOWSKI, Arch. Internat. de Phys., 1904, 1, 359; Arch,
f. Phys., 1904, Supp. Bd., 323 (isolated -uterus movements). LOEB (L.),
J. Am. Med. Ass., 1908, 50, 1897; Arch. f. Entwick. d. Org., 1909, 27,
89 (production of deciduomata). OTT and SCOTT, J. Exp. Med., 1909, 11,
326 (action of glandular extracts on uterus contractions).
Menstruation — (Estrus. — HAMMOND and MARSHALL, Proc. Roy. Soc., 1914,
B 87, 422 (correlation between ovaries, uterus, and mammary glands).
HEAPE, Brit. Med. J., Dec. 24, 1898 (monkeys). KING (J.), Am. J. Phys.,
1914, 34, 203 (cardio-vascular and temperature variations in women).
LOEB (L.), Biol. Bull., 1914, 27, i (correlation between cyclic changes in
uterus and ovaries). MARSHALL and RUNCIMAN, J. Phys., 1914, 49, 17
(ovary and oestrus). MARSHALL and JOLLY, Phil. Trans. Roy. Soc., 1905,
198, 99 (dog) .
Fertilization. — FISCHER and OSTWALD, Pfliiger's Arch., 1905, 106, 229
(physico-chemical theory). GORHAM and TOWER, Am. J. Phys., 1903,
8, 175. LOEB (J.), Pfluger's Arch., 1904, 103, 257; ib., 104, 325; LTniv.
of Calif . Pub., 1903-7; Harvey Lecture, New York, 1911 ; Am. Naturalist,
1915, 49, 257 (conditions determining entrance of spermatozoon) ; Arch. f.
Entw. d. Org., 1914, 11, 301; Science, Nov. 6, 1914 (ultraviolet light).
LYON (E. P.), Am. J. Phys., 1909, 25, 199 (catalase). MORGAN (T. H.),
Science, Feb. 18, 1898. NEMEC, Fertilization Processes, Berlin, 1910.
MATHEWS (A. P.), Am. J. Phys., 1902, 6, 216; ib., 1907, 18, 89. ROBERT-
SON (T. B.), Soc. Exp. Biol. Med., 1912, 9, 90 (docytase); J. Biol. Ch.,
1912, 11, 339; ib., 12, i, 163. SCHUCKING, PflQger's Arch., 1903, 97, 58.
Artificial Parthenogenesis. — FISCHER (M. H.), Am. J. Phys., 1902, 7, 301;
1903, 9, 100. GREELEY, ib., 1902, 6, 296 (produced by loivering of tem-
perature). HARVEY (E. N.), Biol. Bull., 1910, 18, 269 (methods). LILLIE
REPRODUCTION 1213
(R. S.), Am. J. Phys., 1907, 18, p. xvi (by raising temperature). LOEB
(J.), Am. J. Phys., 1900, 4, 178, 423; Die Chemische Entwickelungserre-
gung des Tierischen Eies, Berlin, 1909; Arch. f. Entwick. d. Org., 1902,
13, 481 (methods); Pfluger's Arch., 1907, 118, 181 (osmotic excitation
of development in sea-urchin eggs); .Proc. Nat. Acad. Sci., 1916, 2, 313
(sex of parthenogenetic frogs) . MATHEWS (A. P.), Am. J. Phys., 1900, 4,
343; ib., 1902, 6, 142 (by mechanical excitation). MCCLENDON, Am. J.
Phys., 1912, 29, 298 (in vertebrates). MORGAN (T. H.), J. Exp. Zool.,
1904, 1, 135 (self-fertilization induced by artificial means).
Sex. — DONCASTER, Determination of Sex, Cambridge, 1914. RIDDLE, Science,
1917, 46, 19. WILSON (E. B.), Soc. Exp. Biol. Med., 1905-6, 3, 19.
Pregnancy. — HASSELBALCH, Skand. Arch. Phys., 1912, 27, i (respiratory
exchange). MURLIN, Am. J. Phys., 1910, 26, 134 (energy metabolism of
pregnant dog) ; ib., 1910, 27, 177 (nitrogen balance). MURLIN and BAILEY,
Arch. Int. Med., 1913, 12, 288 (protein metabolism).
Abderhalden Reaction. — BOLDYREFF, J. Phys., 1917, 51, p. xxii. BRONFEN-
BRENNER, J. Lab. Clin. Med., 1915, 1, 79. WELLS (H. G.), ib., 1, 175.
WILLIAMS and PEARCE, Soc. Exp. Biol. Med., 1913, 10, 73. VAN SLYKE
ET AL., J. Biol. Ch., 1915, 23, 377-
Development of Egg. — ABDERHALDEN, Pfluger's Arch., 1915, 147, 99 (com-
pounds which influence development). BABAK, Pfluger's Arch., 1905, 109,
78 (central nervous system and metamorphosis of frog). BROWN (O. H.),
Am. J. Phys., 1905, 14, 354 (permeability of egg). EAVES, J. Phys., 1910,
40, 451 (fat transformations in eggs in- development) . HARVEY, J. Exp.
Zool., 1910, 8, 355 (membrane formation) . HULTON, J. Biol. Ch., 1916,
25, 227 (ferment production in response to introduction of placenta). HYDE
(1. H.), Am. J. Phys., 1904, 12, 241 (differences of potential in developing
eggs). KROGH, Z. f. Allg. Phys., 1914, 16, 163 (temperature and rate of
embryonic development). LOEB (J.), Biol. Bull., 1915, 29, 103 (membrane
formation). LOEB and WASTENEYS, Bioch. Z., 1911, 37, 401 ; J. Biol. Ch.,
1913, 14, 355, 459; ib., 1915, 21, 153 (influence of bases on development
and oxidations in sea-urchin eggs). LILLIE (R. S.), Am. J. Phys., 1916,
40, 249; ib., 1917, 43, 43 (permeability). LYON, Am. J. Phys., 1904, 11,
52 (rhythms in cleavage). LYON and SHACKELL, J. Biol. Ch., 1909, 7, 371-
(autolysis of fertilized and unfertilized eggs). MATHEWS (A. P.), J. Biol.
Ch., 1913, 14, 465 (chemical difference between sea-urchin and starfish eggs),
MCCLENDON, Am. J. Phys., 1912, 31, 131 (effect of alkaloids) ; ib., 1915,
38, 163 (development and permeability). MELTZER, Am. J. Phys., 1903,
9, 246 (effect of agitation). MOORE (A. R.), J. Biol. Ch., 1917, 30, 5
(cytolysis in echinoderm eggs). MALCOLM (J.), J. Phys., 1901, 27, 356
(composition of egg-yolk). MENDEL and LEAVENWORTH, Am. J. Phys.,
1908, 21, 77 (changes in purin, cholesterol, etc., content in development).
RIDDLE (O.), Am. J. Phys., 1916, 41, 409 (metabolism of egg-yolk in
incubation). RIDDLE and BASSETT, ib., 41, 425 (effect of alcohol on size
of egg-yolk). ROBERTSON, Soc. Exp. Biol. Med., 1912, 9, 61 (sea-urchin
eggs). SHACKELL, Science, 1911, 34, 573 (phosphorus metabolism in
echinoderm eggs) .
Metabolism of Embryo. — JONES and AUSTRIAN, J. Biol. Ch., 1907, 3, 227
(nuclein ferments) . LOGHEAD and CRAMER, Proc. Roy. Soc., 1908, B 80,
263 (glycogenic changes in placenta and foetus). MENDEL and LEAVEN-
WORTH, Am. J. Phys., 1907, 20, 117 (glycogen in embryo). MENDEL and
MITCHELL, ib., 20, 81 (inverting enzymes of alimentary tract in embryo);
ib., 20, 97 (enzymes in purin metabolism). WELLS and CORPER, J. Biol.
Ch., 1909, 6, 469 (purin metabolism of foetus and placenta). ZUNTZ and
HASSELBALCH. Skand. Arch. Phys., 1900, 10, 149 (COZ production in
embryo) .
Placenta. — CHARRIN, Arch, de Phys., 1898, 703 (transmission of toxins from
foetus to mother). FAMULENER, J. Infect. Dis., 1912, 10, 332 (transmission
of immunity from mother to offspring). FENCER, J. Biol. Ch., 1917, 29,
I2i4 BIBLIOGRAPHY
19 (composition). LEDERER and PRIBRAM, Pfliiger's Arch., 1910, 134,
531 (relation of placenta and mammary gland) . LOB and HIGUCHI, Bioch.
Z., 1909, 22, 316 (enzymes). LOEB (L.), J. Am. Med. Ass., 1909, 53, 1471
(maternal placenta and function of corpus luteum). ROSENHEIM, J. Phys.,
1909, 38, 337 (pressor principles from placenta) . WERTHEIMER andl MEYER,
Arch, de Phys., 1890, 193 ; 1891, 204 (exchanges between mother and
foetus) .
Parturition. — HEALY and KASTLE, Soc. Exp. Biol. Med., 1912, 9, 48 (internal
secretion of mammary gland as a factor) .
Chemistry of Milk. — MILROY, Bioch. J., 1915, 9, 217 (reaction). OLSON, J.
Biol. Ch., 1908, 5, 261 (proteins). OSBORNE and WAKEMAN, ib., 1915, 21,
539; ib., 1916, 28, i (phosphatids) . RAUDNITZ, Ergeb. d. Phys. (Bioch.),
1903, 193- VAN SLYKE and BOSWORTH, J. Biol. Ch., 1914, 19, 73 (casein) ;
ib., 1915, 20, 135; ib., 1916, 24, 173 (goat's milk).
Human Milk. — BOSWORTH, J. Biol. Ch., 1915, 20, 707; BOSWORTH and VAN
SLYKE, ib., 1916, 24, 187. HAMMETT, ib., 1917, 29, 381 (after parturition) .
HOLT, COURTNEY and FALES, Am. J. Dis. Child., 1915, 10, 229 (salts).
MEIGS and MARSH, J. Biol. Ch., 1913, 16, 147 (human and cow's). SIKES,
J. Phys., 1906, 34, 464 (P and Ca).
Colostrum. — ST. ENGEL, Ergeb. d. Phys., 1911, 41. KASTLE and HEALY, Soc.
Exp. Biol. Med., 1912, 9, 44; WOODWARD, J. Exp. Med., 1897, 2, 217
(chemistry) .
Secretion of Milk. — BASCH, Ergeb. d. Phys. (Bioch.), 1903, 326. — CASPARI,
Arch, f . Phys., 1899, Supp. Bd., 267 (source of milk fat). BOWEN, J. Biol.
Ch., 1915, 12, ii (passage of food and fatty acids into mammary glands).
CAMPBELL (J. A.), Q. J. Exp. Phys., 1913, 7, 35 (chemistry of mammary
gland). GAINES, Am. J. Phys., 1915, 38, 285 (lactation). HAMMOND (J.),
Q. J. Exp. Phys., 1913, 6, 311 ; HILL and SIMPSON, ib., 1914-15, 8, 103, 377
(pituitary extract). HAMMETT and McNEiLE, J. Biol. Ch., 1917, 30, 145
(effect of placenta). HILL and SIMPSON, Am. J. Phys., 1914, 35, 361 ; ib.,
1915, 36, 347 (effect of pituitary extract). MARSHALL and KIRKNESS,
Bioch. J., 1906, 2, i; PATON and CATHCART, J. Phys., 1911, 42, 179;
PORCHER, Arch. Internal. Phys., 1909, 8, 356 (lactose formation). MAC-
KENZIE (K.), Q. J. Exp. Phys., 1911, 4, 305; SCHAFER and MACKENZIE,
Proc. Roy. Soc., 1911, B 84, 16 (action of animal extracts). MOORE and
PARKER, Am. J. Phys., 1900, 4, 239 (lactose formation) . OTT and SCOTT,
Soc. Exp. Biol. Med., 1912, 9, 63 ; SCHAFER, Q. J. Exp. Phys., 1913, 6, 17
(affect of pituitary and corpus luteum) ; ib., 1915, 8, 379 (pituitary extract).
Correlation of Mammary Gland with Other Sexual Organs. — BIEDL and
KONIGSTEIN, Z. Exp. Path. Ther., 1910, 8, 358 (hormone which excites
mammary gland in pregnancy). HEAPE, J. Phys., 1906, 34, p. i. LANE-
CLAYPON and STARLING, Proc. Roy. Soc., 1906, B 77, 5°5- LOEB (L.)
and HESSELBERG, J. Exp. Med., 1917, 25, 285, 305 (correlation in cycle of
uterus, ovaries, and mammary gland). O'DONOGHUE, J.Phys., 1911, 43,
p. xvi (corpus luteum and mammary gland).
fltrowth. — CRAMER, J. Phys., 1916, 50, 322 (the biochemical mechanism erf
growth). HATAI, Am. J. Phys., 1907, 18, 309 (rat). LOEB (J.), Science,
1915, 41, 169 (simplest constituents required for growth in an insect).
ROBERTSON (T. B.), Am. J. Phys., 1915, 37, i, 74 (pve- and post-natal
growth of man). OSBORNE and MENDEL, see Chapt. X.
Anastomosis of Bloodvessels. — CARREL (A.) and GUTHRIE (C. C.), J. Am. Med.
Ass., 1906, Nov. 17, p. 1648 (kidney transplantation); Surg. Gyn. Obst.,
1906, 2, 266 (veins). CARREL, J. Exp. Med., 1910, 12, 139; ib., 1912, 15,
388; ib., 16, 17 (aorta). GUTHRIE, Heart, 1910, 2, 115 (survival of engrafted
organs). CARREL, J. Exp. Med., 1907, 9, 226; GUTHRIE, Am. J. Phys.,
1907, 19, 482 (hetero-transplantation of bloodvessels). GUTHRIE, Blood-
vessel Surgery, London, 1912. CARREL, Johns Hopk. Bull., 1906, 17,
236 (surgery of bloodvessels) . GUTHRIE, J. Am. Med. Ass., 1908, 50, 1035.
REPRODUCTION 1215
Transplantation of Organs. — QARREL, J. Exp. Med., 1910, 12, 146 (remote
results of replantation of kidney and spleen). GUTHRIE, ib., 12, 269 (sur-
vival of engrafted ovaries and testicles). GUTHRIE and LEE, J. Am. Med.
Ass., 1915, 64, 1823 (ovarian transplantation). GUTHRIE, Arch. Int.
Med. ,1910, 5, 232 (kidney, perfused or not). MURPHY (J. B.), J. Exp. Med.,
1913, 17, 482 (transplantability of tissues to the embryo of foreign species) ;
ib., 1914, 19, 513 ; ib., 19, 181 (ultimate fate of mammalian tissue implanted
in chick embryo) . LOEB and ADDISON, Arch, f . Entwick. d. Org. , 1909, 27,
73 (hetero-plastic skin transplantation). LOEB (L.), J. Am. Med. Ass.,
1915, 64, 725 (changes in chemical environment and growth of tissues);
J. Med. Res., 1917, 37, 229 (kidney tissue). (See also Chapter XI.)
Tissue Cultures. — BAITSELL, J. Exp. Med., 1915, 21, 455 (origin of a fibrous
tissue in cultures of adult frog tissues). CARREL and BURROWS, J. Exp.
Med., 1911, 13, 387; LAMBERT, ib., 1916, 24, 367 (technique); ib., 13, 416
(thyroid). CARREL, J. Exp. Med., 1913, 18, 287 (connective tissue) ; ib., 17,
14 (activation of growth of connective tissue) ; ib., 1912, 15, 516; EBELING,
ib., 1913, 17, 273 (permanent life of tissues outside of the organism).
INGEBRIGTSEN (R.), J. Exp. Med., 1913, 18, 412 (regeneration of axis
cylinders in vitro) ; ib., 1916, 23, 251 (life of peripheral nerves in plasma).
LOEB (L.), Untersuch. iiber Umwandlungen u. Thatigkeiten in d. Geweben,
Chicago, 1897. LOSEE and EBELING, J. Exp. Med., 1914, 19, 593 (human
tissue). LAUBT (R. A.), J. Exp. Med., 1913, 18, 406 (influence of tempera-
ture and medium on survival of embryonic tissue in vitro). LEWIS (M. R.
and W. H.), Am. J. Phys., 1917, 44, 57 (contraction of smooth muscle cells
in tissue cultures). NEWMANN and BURROWS, Am. J. Phys., 1917, 42,
597 (effect of amino-acids and peptones on growth of cells in vitro) . WALTON,
J. Exp. Med., 1915, 22, 194 (production of substances inhibiting cell-growth) ;
ib., 1914, 20, 554 (effect of tissue extracts on growth in vitro). WEIL, J. Med.
Res., 1912, 26, 159 (tissue cultures in vitro). UHLENHUTH, J. Exp. Med.,
1915, 22, 76 (skin); ib., 1914, 20, 614.
Parabiosis. — Rous, Soc. Exp. Biol. Med., 1909, 7, 8 (test for circulating anti-
bodies in cancer).
INDEX
References to the Practical Exercises are in black figures.
ABDOMINAL breathing, 230
muscles in expiration, 229
Abducens, or sixth nerve, 926
Aberration, chromatic, 1027, 1063, 1106
spherical, 1027, 1063, 1106
Absorption, 426
and lipoid solubility, 437
coefficient of gases, 247
comparative physiology of, 431
factors concerned in, 435
from the peritoneal cavity, 439
from the stomach, 433
gas exchange in intestine, 436
in large intestine, 451
intra- and inter -epithelial, 446
of bile-constituents in jaundice, 384
of cane-sugar, 436, 464
of carbo-hydrates, 445
of fat, path of, 443, 463
of gases in blood, 250
of iron, 447
of light, 1012
of proteins, 447
of the food, 431
physical introduction to, 426
theories of, 433-436
of water and salts, 422, 446
osmosis and diffusion in, 435
parenteral, 446
Acapnia and blood -pressure, 184
and mountain sickness, 298
and shock, 192
Acceleration of heart by sipping water,
171,210
Accelerator nerves of heart, 157, 162,
166, 197, 199
Accessory auditory nucleus, 928
dietetic factors, 617
vagus nucleus, 929
Accommodation, 1020
mechanism of, 1022
pupil in, 1023
Acerebral tonus, 942, 955
Acetaldehyde, 544, 562
Acetone, 562
and katabolism of fatty acids, 567
Acetone in diabetes, 529, 555
in urine, 529
Aceto-acetic acid, 562, 567
in diabetes, 555
A.C.E. mixture, 63
Acetic acid, 556
Acid albumin, 352, 458
Acidity of gastric juice, 350, 417
Acidosis, 24, 282, 555
Acrolein, 12
Action currents, 823, 824, 830, 842
and functional activity, 825
diphasic. 825
double conduction of, 792
electromotive force of, 827
in polarized nerves, 831
in voluntary contraction, 762
monophasic, 825
of central nervous system, 838
of eye, 839
of glands, 838
of heart, 88, 833-838, 844
of muscle, 823, 843
of phrenic nerves, 827
of skin, 838
of spinal cord, 838, 849, 895
of vagus, 828
of veratrinized muscles, 829
propagation of, 824
rate of propagation of varia-
tion, 827
reflex, 913
theories of, 828
Adamkiewicz's reaction of protein, 8
Adaptation of digestive juices to food,
371, 398, 405, 409- 4i4
of retina, 1047, 1058
Addison's disease and adrenals, 655
Adenin, 481, 592, 593
Adequate stimuli, 901, 1007
Adipocere, 564
Adiposophilia, 569
Adrenal bodies, 655
epinephrin content of, 664
relation of, to coagulation, 45
secretory nerves of, 661
1216
INDEX
1217
Adrenal cortex, function of, 665
Adrenalin, action of, on artery rings, 66,
216
on coagulation time, 45, 656
on heart, 655
on nerve-endings, 182, 655
on pupil, 656,
on sympathetic, 655, 1005
on vaso-motors, 173, 179. 655
on veins, 181
action of small doses of, 660
arterio-sclerosis, 660
artificial, 665
assay of, 453, 656
biological tests for, 46, 656
chemistry of, 664
formation of, 665
function of, 657
glycosuria, 550
secretory influence of nerves on,
661
Adsorption, 430
Aerotonometer, 258
/Esthesiometer, compasses, 1115
Prey's hair, 1080, 1114
Afferent impulses, decussation of, 894
paths, 892
scheme of, 880
After -brain (myelencephalon), 850.
After-images, 1055, nil
Agglutination, 30,71
by foreign serum, 71
Agglutininogens, 31
Agraphia, 970
Alanin, 2, 360, 574. 59»
formation of dextrose from, 538
Alanyl-glycyl-tyrosin, 449
Albinos, intravascular clotting in, 43
Albuminates or derived albumins, 9
Albuminoids, 2
Albumins, 2, 9
heat -coagulation of, 9
in urine, 488, 497, 499, 524, 525
Albumoses, 3
action of, on blood -pressure, 173,215
on coagulation, 37, 45
in peptic digestion, 352
tests for, in urine, 525
Albumosuria, 489, 525
Alcohol, 630
action of, on respiratory centre, 191,
631
on gjastric secretion, 630
in diet, 630
poisoning, blood -pressure curve in,
191
precipitation of proteins by, 8
Alcohols, relation of, to carbohydrates, 3
Aldehydase, 272
Aldehydes, relation of, to carbo-hydrates,
3, 543. 544- 545. 5^1
Aldohexoses, 543
Aldol, 562
Algometer.ioSg
Alimentary canal, anatomy of. 319
length of, 320
time of passage through, 334
glycosuria, 540, 717
Alkali-albumin, 10, 461
Alkalinity of blood, etc., titratable. 25
Alkaptonuria, 483, 581
Allantoin, excretion of, 596
Allantois, 1128
4 All-or-nothing ' law, 154
Alloxuric bodies, 481
Alveolar air, partial pressure of gases in,
241, 263
Amblyopia after occipital lesion, 966
Amboceptors, 28,73
Amide-nitrogen in proteolysis, 360
Amino-acetic acid, 2
Amino-acids, i, 360, 352, 417, 562
absorption of, 449, 450
changes in liver, 584
chemical nomenclature of, 360
conversion of, into glycogen and
dextrose, 536, 538, 590
formation of, from tissue-proteins,
578
of urea from, 582, 584, 586, 588,
624
in blood, 574
in liver diseases, 586
in phosphorus poisoning, 563
in urine, 481,488
metabolism of, 582
synthesis of, by bacteria. 618
Amino-bodies, deaminization of, 588
Amino-succinic acid, 360
Amino-valerianic acid, 360
Ammonia, action of, on muscle, 759
impermeability of lungs for, 240
in proteolysis, 360
in the blood, source of, 585, 588
after Eck's ftstula, 585
in urine, 480, 521
reflex in hibition of heart by, 170.
210
Ammonium salts, formation of urea
from, 584, 588
sulphate, precipitation of proteins
by, 8, 525
Amnesia, 970
Amnion, 1128
Amniotic fluid, 1128, 1134
Amoeba, 6, 16, 732
Amoeboid movements, 732
Ampire, 725
Amylase, 345, 346
pancreatic, 358, 362,461
salivary, 346, 417,455
Amyi nitrite, action on pulse, 106
formation of methgemoglobi.i
by, 53
77
1218
INDEX
Amylolytic stage of gastric digestion.
348,356,417
Amylopsin, 358, 362, 461
influence of bile on, 370
Anabolic changes in living matter, 6
Anacrotic pulse, 106
Anaesthesia by A.C.E. mixture, 63
by chloral, 217
by chloroform (Gr6hant's method).
2O2
by morphia, 63, 201
by pressure on brain, 985
by urethane, 217
for animals, 63
Anaphylaxis, 32
Anastomosis of nerves, 975
of bloodvessels, 1 145
Anelectrotonus, 786, 844, 845,
Angular gyrus and vision, 966
Animal board, 201, 214
Animal heat, 674
Animals, localization in different, 980
Anions, 429
Ankle-clonus, 915
Annulus of Vieussens, 157, 162, 179
Anode, 429, 724
Anterior commissure, 922, 893
horn, cells of, 858, 864, 876
connections of, 876
roots, 797, 876
Antero-lateral ascending tract, 866, 873,
886
connections of, 873
descending tract, 867
connections of, 884
ground bundle, 867
Antibodies, 31, 648
Antidiabetic diet, 554, 556
' Antidromic ' nerve impulses, 181, 792,
807
Antiferments, 339, 390, 343
in intestinal parasites, 390
Antigens, 31
Antikinase, 44, 391
Antilytic secretion, 398
Antimony and protein metabolism, 563
Antiperistalsis, 330, 332, 421
Antipyretics, 704
Antithrombin, 38, 39, 42, 44
Antitrypsin, 343. 390
Antrum pylori, 326, 327
Aorta, effect of compression of, 204
Aortic insufficiency, effect of, on pulse,
106
notch, 96
stenosis, effect of, on pulse, 107
valves, 87, 96, 206
and dicrotic wave, 104
Apex-beat, 90,201, 207
Apex preparation of heart, 143, 194
Aphasia. 968
Aphasia, Broca's, 970
Aphasia, motor, 970
sensory, 970, 972
subcortical, 972
temporary, 972
Wernicke's', 971
Aphemia, 971
Apncea, 283, 300
vagi, 284
vera, 283
Apocodeine, action of, on vaso-motors,
173
Appetite, 1099
juice, 1099
Aqueduct of Sylvius, 874
Aqueous humour, 58
composition of, 466
secretion of, 1016
Arachnoid, 86 1
Arachnolysin, action of, on erythrocytes,
28
Arcuate fibres, internal, 873
Arginase, 587
Arginin, 360, 587
Argyll-Robertson pupil, 1025
Arhythmia, respiratory, 287
Aromatic sulphates in urine, 484, 517
Arsenic and protein metabolism, 563
Arterial blood -pressure, amount of, 112
Arteries, blood-pressure pulse in, 109
structure of, 82
to insert cannulae into, 63
tone of, 185, 918
Artery rings, action of adrenalin on, 216
action of serum on, 46
Arterioles, resistance in, 129
Arteriosclerosis, velocity of pulse in, 109
Artificial respiration, 2O2, 230
with oxygen, 204
Ascending degeneration, 866
Aspartic acid, 360
Asphyxia, 178, 283, 187
condition of haemoglobin in, 51
effect of, on circulation, 172, 187,
213
glycosuria caused by, 548
in the foetus, 1137
influence of, on blood -pressure, 213
Assimilation limits for carbohydrate, 540,
551.637
Association areas, 973
centres, 962, 973
fibres, 883, 885
Asthma, spasmodic, and bronchial mus-
cles, 287
Astigmatism, irregular, 1028
regular, 1031, 1062, 1105
Astrospheres, 1122
Atrio-ventricular bundle. See Auriculo-
ventricular bundle
Atropine, action of. on heart, 166, 199
on nerve-cells, 182
on pupil, 1026
INDEX
1219
Atropine, action of, on salivary secre-
tion, 392, 396, 457
Attraction sphere, 5, 851, 1079
in nerv«-celts, 851
Auditory centre, 928, 966
nerve, 927, 1069
cochlear division of, 928
vestibular branch of, 928
ossicles, 1066, 1069
path, scheme of, 927
Auerbach's plexus, 319, 330
Augmentation of heart-beat, 157, 172,
199
nature of, 167
primary, 159
secondary, 159
Augmentor nerves, effect of, on quiescent
heart, 168
Aura, 973
Auricular canal, 81
fibrillation, 151
nutter, 151
pressure curve, 98
Auriculo-ventricular bundle, 81, 135,
- 138- 147
pulse-tracings in disease of, 149
junction, stimulation of, 198
node, 81, 147
valves, 89,206
moment of opening of, 96
Auscultation of breath-sounds, 231, 304
of heart-sounds, 207
of lungs, 304
Auto-digestion of stomach, 389, 465
Autogenetic theory of nerve regenera-
tion, 80 1
Autolysis, 578
Automatic actions of spinal cord, 916
Autonomic nervous system, 892, 1003
functions of, 1005
Avalanche theory, 785
Aviator's sickness, 299
Axial strand fibrils, 80 1
Axis-cylinder or axon, 781, 852, 855
bifurcation of, 802
fibrils in, 851
growth of, in cultures, 803 857,
Axon-reflexes, 400, 792, 913
Babinski's sign, 915
Bacteria and digestion, 422, 423
in faeces, 424
in intestine, 343, 423, 618
synthesis of amino-acids by, 618
Bactericidal action of gastric juice, 356
Balloon ascents, deaths in, 298
Baryta, absorption of carbon dioxide by,
240
Basal ganglia. 932
metabolism, 686
Basilar membrane, 1067, 1070
Bat's wing, contractile vessels of, 81, 180
Batteries, 197, 724
Beats (hearing), 1113
Beaumont on digestion, 349
Bcchterew's nucleus, 928
Btfckmann's apparatus, 427, 529
Bellows recorder, 302 i
Bell's experiments on nerve-roots, 891
Belt recorder for respiration, 233
Benedict estimation of blood sugar, 717
Benzoic acid, 481, 580
Beri-beri caused by polished rice, 632
thymus in, 633
Bert on double conduction in nerves, 792
on effects of oxygen at high pres-
sure, 297
Betz cells, 848, 875, 959
Bichromate cell, 197
Bidder's ganglia, 141
Bile, 363-370
absorption of, 384, 412
acids, 365, 462
circulation of, 412
formation of, 384
Hay's test for, 462
Pettenkofer's reaction, 366, 462
adaptation of, to food, 413
and absorption of fat, i6g
and pancreatic juice, adjuvant
action of, 367
and surface tension, 369, 462
as an excretion, 424
composition of, 363
curve of secretion of, 413
digestive functions of, 367
formation of, 384, 385
freezing-point of, 387
gases of, 267, 366
in emulsification of fats, 367
influence of nerves on secretion of,
411
inhibition of heart by, 172
mucin, 364
pigments, 364, 385, 462
circulation of, 412
Gmelin's test for, 365, 462
production of, in liver, 385
relation of, to spleen, 672
precipitation of gastric digest by,
370
quantity of, 367
rate of secretion of, 413, 419
reactions of, 462
reinforcing action of, 368
salts, 365
action of, on blood, 28, 70
decomposition of, 365
in urine, Hay's test, 528
'influence of, on secretion of
bile, 413
secretion of, influence of nerves on,
411
influence of secretin on, 408, 412
INDEX
Bile, secretory pressure of, 414
spectrum of, 365
Biliary fistula, 369, 412
Bilirubin, 364
Biliverdin, 364
Bioplasm. See Protoplasm, and Living
matter
Bipolar ganglion cells, 856
Bird's blood, coagulation of, 36, 43
Biuret reaction, 8, 459
Bladder, 510
pressure in, in micturition, 510
Blastoderm, 1125
Blind spot, 1044, 1064, 1107
mapping the, 1064
Blood, bird's, 36
carbon dioxide content of, 26, 255
chemical composition of, 47
circulation of, 80
coagulation of, 33, 62
composition of, 49
-corpuscles, coloured, composition
of, 50
osmotic resistance of, 73
crenation of, 16
destruction of, 21
dextrose in, 50, 540, 717
• enumeration of, 18, 67
formation of, in embryo, 20
gaseous metabolism of, 252
life-history of, 20
in pernicious anaemia, 21
red, 15
destruction of, 2 1
origin of, 20
rouleaux formation of, 16
shadows or ghosts of, 70
size of, 15
structure of, 15
white. See Leucocytes
distribution of, 56, 189
electrical conductivity of, 26. 68
flow, calorimetric method of mea-
suring, 122
in different organs, 127
in feet, 127
in hands, 126
measurement of, 219
functions of, 59
gases of, 245-266
estimation by ferricyanide, 250
quantity of, 250
tension of, 258
results, 261
guaiacum test for, 76
kinetic and potential energy of cir-
culating, 119
laking of, 70
measurement of velocity of, 120-124
morphology of, 14
opacity of, 70
pigment, microscopic test for. 78
Blood pigment, preparation of, 73
plasma, proteins of, 47, 572
relative volume of, 27, 68
plates, 18
platelets and coagulation, 39, 40
anticoagulants and preserva-
tion of, 40
disintegration of, 40
functions of, 62
precipitin test for, 31
quantity of, 55
in lungs, 224
which may be lost, 191
reaction of, 24, 62
regeneration of, 22
relative volumes of corpuscles and
plasma, 27, 68
serum, electrical- conductivity of,
26, 27, 68, 386
freezing-point of, 386
specific gravity of, 26, 62
sugar in, 47, 499, 502, 533, 540, 547
549, 55i, 552, 636, 657, 717
temperature of, 680, 711
testing for adrenalin in, 656, 657, 662
tests for, 45-47
titratable alkalinity, 25
vaso-constrictor property of shed, 45
velocity of , 117-127
in arteries, 119, 125
in capillaries, 120, 130
in veins, 120, 134
measurement of, 120, 122, 219
vessels, suturing, 1144
viscosity of, 23, 502
volume of corpuscles and plasma
27,68
why it does not clot in the vessels,
45
Blood-pressure, arterial, measurement of,
107
and acapnia, 184
curves with elastic manometers, 93,
in
with mercurial manometers,
no, 112, 210
effect of changes of posture on, 190,
213
of extracts of bone-marrow on,
671, 673
of freezing the cord on, 184
of hemorrhage and transfusion
on, 191, 214
of kidney on, 671
of muscular exercise on, 115,213
of nervous tissue on, 673
of peptone on, 173, 215
of pituitary on, 668
of proteoses on, 173, 215
of suprarenal on, 171, 216, 655
of testicle on, 642
of thymus on, 645
INDEX
1221
Blood- pressure, estimation of the arterial,
210, 213
*—*f actors which maintain, 116
fall of, in sleep, 986
hydrostatic and hydrodynamic ele-
ments, 190
in capillaries, 130, 131
influence of respiration on, 289
in man, influence of exercise on, 115,
measurement of, by stetho-
scope, 113, 213
in pulmonary artery, 116
in right and left ventricles, 116, 138
mean arterial, 109, 112
measurement of, 109, 211
permanent element in, in
systolic and diastolic, 113
tracings, 165, 184, 186, 187, 188, 191,
210, 213, 216, 237, 279, 280
Blood-pump, 249
Blood-serum, freezing-point of, 386
Blood-supply, regulation of, 189
Bloodvessels, anastomosis of, 1144
rhythmically contractile, 8 1, 175, 180
structure of, 82
tone of, 184, 996
Body, composition of, 601
Bohr, on blood-gases, 254, 261, 264
Bolometer, 675, 783
Bone-marrow and blood-formation, 20,
'22
action of extracts of, 671, 673
Bones, composition of, 601, 621
influence of pituitary on, 670
of testicles on, 642
• Boot ' electrodes, 842
Brain, anemia of, 986
chemistry of, 991
circulation in, 989
condition of, isolated, 975
in sleep, 913
development of, 849
functions of, 931
heat-production in, 689
influence of, on spinal reflexes, 910,
IOOI
respiratory changes in volume of,
295
resuscitation of, 990
size of, at different ages, 988
and intelligence, 988
temperature of, 712
volume, respiratory variations in,
295
Bread, 720
Breast-feeding, superiority of, 1140
Breath, holding, 234
Broca's area, 971, 974
aphasia, 970
Bronchi, 223
movements of, in respiration, 231
nerves of, 287
Bronchial breathing, 231
muscles, innervation of, 287
Bronchoscope, 231
Brownian motion, 454
Brown-Sequard's syndrome, 894
Brunner's glands, 380, 383
' Buffy ' coat, 39
Burdach's tract, 866
connections of, 870
Burdon-Sanderson on negative variation,
825, 826
Burns, superficial, death from, 299
Buttermilk diet, 422
Butyric acid, 562
fermentation, 423
Cachexia strumipriva, 648
Cajcum, nerves of, 332
Caffeine, 481, 583, 594, 632
as diuretic, 509
Caisson disease, 297
Calcium and bone formation, 621
deficiency of, 621
relation of, to heart-beat, 152, 20O
Calorimeter, air, 679
differential micro-, 680
respiration, 240, 676, 678, 721
Atwater's, 676
water equivalent of, 721
Calorimetric method for blood- flow in
hands, 219
for vaso-motor reflexes, 188, 221
Calorimetry, 675,721
Campbell, visuo-psychic area of, 966
Cancer, gastric juice in, 350
Cane-sugar, absorption of, 435, 445, 464
inversion of, 10, 339
by gastric juice, 356
tests for, n
Cannula, three-way, 212
gastric, 459
to put into an artery, 63
trachea, 202
vein, 215
Capillaries, blood- pressure in, 131
changes of calibre of, 173
circulation in, 120, 129, 193
pulse in, 131
resistance in, 120, 130
total cross-section of, 130
velocity of blood in, 130
Capillary electrometer, 728, 729, 842
Caproic acid, 566
Capsule, internal. See Internal capsule
Carbo-hydrates, absorption of, 445
amount of, in standard diet, 623, 625
assimilation limits, 540, 551, 637
composition of, i, 3
constitution of, 3
intermediary, metabolism of, 542
in diabetes, 553
metabolism of, 533
INDEX
Carbo-hydrates.Molisch's test for, II
necessity of, in nutrition, 607
passage of, through placenta, 1131
protein-sparing action of, 606
reactions of, IO
tests for, 10
tolerance after pancreatectomy, 637
Carbon balance-sheet, 618
equilibrium, 618
dioxide, action of, on respiratory
centre, 281
and blood- flow in heart, 178
distribution in blood, 255
estimation of, 240, 305
excretion, influence of forced
respiration on, 245
mechanism of, 264
in alveolar air, 241
in blood, condition of, 257
in foetal blood, 1129
influence on hemoglobin, 255
in serum, 255, 256
in venous blood, tension of, 261
partial pressure of, in alveoli,
261, 264
in blood, 259, 261
in tissues and liquids,
272, 273
production, Haldane's appara-
tus for measuring, 304, 305
production of, in different
animals, 244
in muscular work, 242
in relation to body-weight,
244
in rigor, 270, 777
tension of, in tissues, 272
washing out of, 245, 283
monoxide method for quantity of
blood, 56
necessary quantity in diet, 625
Carbonic acid and urea formation, 589
oxide haemoglobin, 53, 74
Cardiac cycle, 85
death, 171
impulse, 90, 208
nerves, 157, 162, 196, 198, 203
sound, 96
sphincter, 320
Cardio-augmentor centre, 169
Cardiogram, 91 , 207
inversion of, 91
Cardiograph, 90, 208
Cardio-inhibitory and augmentor centres,
169
tone of, 169
Cardiometer, 139
Cardiophonogram, 88
Cardiopneumatic movements, 128, 303
Carnosin in muscle, 767
Casein, 354
as adequate protein, 613
Caseinogen, 354, 719
Castration, effects of, 640, 642
on thymus, 644
Catalase, 76, 271
Catalysers, 339
Catheterism, 716
Catheter, pulmonary, 259
Cells, structure of, 4
Cellulose, digestion of, 423
Central canal of cord, 849, 861
grey axis, 861
nervous system, action currents of,
838
arrangement of white and
grey matter in, 86 1
development of, 849
functions of, 887
'general arrangement of,
861
histological elements of,
850-861
localization of function in,
975
methods of study of, 848
structure of, 847
Centre for smell, 967
for taste, 968
of gravity of body, 946
thumb, 973
Centres, cardio-inhibitory and augmen-
tor, 169
heat, 701
' motor,' of cortex, 1001
musical, 967
of cord and bulb, 919
sensory, of cortex, 965-968
vaso-motor, 182-185
Centrifuge, 64
Centrosome, 5, 851
in the ovum, 1122
Cerebellar ataxia, 935
Cerebellum, anatomical division of, 942
connections of, 885, 935
functions of, 933 •
inferior peduncle of, 885
localization of function in, 942-944
middle peduncle of, 886
peduncles of, 885
structure of, 934
superior peduncle of, 886
worm of, 874, 885, 942
Cerebral anaemia, 190, 986, 989, 990
stimulation of vagus after, 187
circulation, 989
cortex, and respiration, 276
clinical and pathological obser-
vations on, 962
development of, 862
functions of, 947
histological differentiation of,
958
inhibition from, 954
INDEX
1223
Cerebral cortex, layers of, 958
localization of function in, 951
' motor ' areas of, 95 1
sensory areas of,. 965
stability of reactions of, 953
hemispheres, excision of, 947-949
frog, 947, 1000
pigeon, 948, IOOI
localization, Flechsig's areas, 961
peduncle, 882
vesicles, 849
Cerebrins, 794, 991
Cerebro-spinal fluid, 58, 466, 992
displacement of, 295
secretion of, 993
Cerebrum, effects of removal of, 947-949
Cervical sympathetic. See Sympathetic
Chalk-stones, 487, 590
Cheese, 626, 719
Chemical regulation of respiration, 281
' Chemical tone,' 695
Chemiotaxis, 61
in nerve regeneration, 800
Cheyne-Stokes respiration, 287, 300
Chiasma, optic, 923
Child, food requirement of, 628
basal metabolism of, 628, 686
gaseous exchange in, 243
Chloral, anaesthesia by, 190, 213
Chlorides, estimation of, 515
Chloroform anaesthesia, inhibition in, 170
passage of, through placenta, 1 1 30
Cholesterol or cholesterin, 4, 47, 570, 794,
991
circulation of, 571
in bile, 366, 41*
reactions of, 463
Cholic acid, 365, 366
Cholin, 4, 421, 571
Cholohaematin, 365
Chorda tympani, 179, 391-393, 456
stimulation, of, 456
Chordo-lingual triangle, 391
Chorion, 1128
Choroidal epithelium, 1016, 1048
Choroid plexus, 992
Chromaffin cells, 665
Chromatin, 5
changes in, in nerve-cells, 983, 984
extranuclear, 984
Chromogen, 482
Chromophanes, 1049
Chromosomes) 6, 1122
Chrysotoxin, action of, on blood-pres-
sure, 173
Chyle, 14, 58, 443
composition of fistula, 58
Chyme, 326
passage of, through pylorus, 327,
408
to obtain normal, 459
Chymosin (vide Rennin), 353
Cilia, 733
movements of, 8il
work done by, 734
Ciliary ganglion, 924
muscle, 924, 1022
nerves, 1033
processes, 1014
and secretion of aqueous hu-
mour, 1016
Cinematograph, 945, 1042
Circulating blood, microscopic examina-
tion of, 193
liquids, 14
Circulation, changes in, at birth, 1138
comparative, 80
cross, through brain, 284
general view of, 81
in brain, 989
in capillaries, 129, 131
in the embryo, 1138
in the frog's web, 15, 193
in the lungs, 137, 223
in the tadpole, 193
influence of posture on, 190, 213
of lymph, 192
time, 135-138
electrical method, 135-137
Hering's method, 135
methylene blue method, 137,
217
pulmonary, 137, 698
Circus movements, 945
Citrates and coagulation, 37
Clarke's column, 864
connections of, 872
Coagulated proteins, reactions of, 9
Coagulation of blood, 42, 62
action of fluorides on, 37
of citrates on, 37
birds, 36
calcium in, 36
factors in, 42
hirudin and, 37
influence of platelets in, 37
of proteoses on, 37
of tissue extracts on, 36
influences restraining, 42
intravascular, 42
leech extract and, 38
manganese and, 37
of crayfish, 40
of Limulus, 40
peptones and, 37
relation of adrenals to, 45
liver to, 44
studied with ultramicroscope,
39
of lymph, 57
temperatufe, to determine, 9
Coagulins, 41
Coal-gas poisoning, 53, 74
Cobra-venom and coagulation, 43
122 4
INDEX
Cbcaine, action of, on nerves, 791
on pupil, 1026
fever, 704
Cochlea, 927, 1067, 1068, 1069
Cochlear root of eighth nerve, 874, 928
Cocoa, 594, 630, 631
Co-enzymes or co-ferments, 343, 368, 548
Coffee, 594, 631, 632
Cola-nut, 632
Cold sensations, 1041, 1082, 1084, 1115
after section of cutaneous
nerves, 1088, 1091
paths for, 896
Collaterals, 781, 852
of posterior root fibres, 871
Colon, movements of, 330, 333
innervation of, 332
Colostrum, 1139
Colour, body and surface, 1012
blindness, 1059, 1112
temporary, 1061
mixing, 1052, III!
triangle, 1054
. vision, 1051
Hering's theory of, 1057
Young-Helmholtz theory of,
1053
Coloured shadows, 1056
Colours, complementary, 1052, 1 068, nil
primary, 1053
Coma, congestion of brain in, 985
diabetic, 555
Comma tract, 867, 871
Commissural fibres, 863, 893
Common path, principle of the, 899
Commutator, Pohl's, 732
Compensator, 727
Compensatory pulse of heart, 155, 156
Complement, 28, 72
Complemental air, 235, 303
Complementary colours, 1052, nil
Condensed air, effects of breathing, 295
Conditioned reflexes, 975
Conduction, double, in nerve, 791
irreciprocal, 792
isolated, law of, 793
loss of heat by, 68 1
Conductivity, molecular, 429
of nerve, 786, 790
anaesthetics and, 790, 814
effect of temperature on, 791
electrical currents on, 786,
787, 844
specific, of electrolytes, 429
Congo-red as test for acids, 351
Conjugate deviation, 965
Conjugated proteins, 2
Conservation of energy, law of, in body,
679, 683
Consonants, 313
Contraction, formula of, 788, 845
for nerves in situ, 789
Contraction, law of, for human nerves, 846
paradoxical, 832, 844
secondary, 832, 842
Contractions, superposition .of , 756, 816
Contrast (vision), 1056
Co-ordination of movements, 945, 981
of reflexes, 908
Core models, and electrotonic currents,
831
Cornea, radius of curvature of, 1017
Corneal reflex, 914
Corona radiata, 862, 875, 883
path from cortex in, 877
Corpora Arantii, 87
quadrigemina, 874, 881, 932
and respiration, 276
anterior, 923, 932
posterior, 928, 932
striata, 850, 862, 870
and temperature regulation, 701
Corpuscles and plasma, relative volume,
27, 68. See Blood
Corpus callosum, 863, 883
dentatum, 863
luteum, 643, 1 1 20, 1 12 1
and menstruation, 1121
haematoidin in, 385
internal secretion of, 643, 1078,
II2I
origin of, 1121
striatum, 850, 862, 870
Cortex of brain, functions of, 947
' motor ' areas of, 95 1
sensory areas of, 965
Cprti, ganglion of, 927
organ of, 927, 1067, 1069, 1074
Cortical epilepsy, 972
grey matter, 86 1
Costal breathing, 229
Cotton seed, 361
Coughing, 288
Cranial conduction of sound, 1071, 1113
nerves, 920
bifurcation of afferent fibres,
924, 925, 926, 928
homologies of, 92 1
nuclei of, 920
Crayfish blood, clotting of, 40
Cream, 718
Creatin, 481, 703
Creatin and creatinin in protein meta-
bolism, 597
in muscle, 768
Creatinin, 481, 523
excretion and muscular work, 6n
in fever, 703
source of urinary, 598
Crenation, 16
Crista acustica, 936
Cross circulation through brain, 284
Crossed pyramidal tract, 866, 875, 879
connections of, 875
INDEX
Crowbar case, American, 974 .
Crura cerebri, 870, 874
Crusta, 870
Cultivation of tissues outside the body,
1142
Cuneate funiculus, 869
nucleus, 869
relation of, to fillet, 874
Cuneus and vision, 966
Cuorin, 571
Curara, 182
action of, on gaseous exchange, 244,
54i
on heat production, 694, 702
on nerve-endings, 182
on skeletal muscle, 738, 811
on vomiting, 336
Curdling of milk by rennin, 353, 354, 459,
7*9
Current intensity and stimulation, 741,
784
of action. See Action current
of rest. See Demarcation current
Cushny's views on urine secretion, 502
Cutaneous burns, death from, 299
excretion, 511
nerves, section of, 1085
respiration, 299
sensations, 1078
Boring's experiments, 1091
cortical centres for, 969
localization of, 1093
Trotter and Davies' experi-
ments, 1085
Cybulski's arrangement (velocity of
blood), 123
Cyclic compounds, 615, 616, 618
Cyclopoiesis, 615, 616, 618
Cystein, 360, 365, 581, 583
Cysteinic acid, 366
Cystinuria, 366, 488, 579
Cytolysins, 31
Cytoplasm, 5
Cytosin, 593
Dancing mice, labyrinth in, 945
Daniell cell, 197, 724
Daphnia, Metchnikoff's researches on, 60
Dark-adapted eye, 1047, 1049, 1058
Daturine, action of, on pupil, 1026
' Dead space,' respiratory, 236
Deaf-mutes, atrophy of temporal con-
volutions in, 967
equilibration in, 940
Decerebrate rigidity, 917, 942, 955,
IOOO
preparation, 998
Decerebrator, 999
Decidua, 1076, 1083
absorption of, by leucocytes, 60
artificial production of, 1078
Decinormal solutions, 479, 522
Decussation of afferent impulses, 894
of efferent impulses, 893
of fillet, 870
of optic nerve, 923, 966
of pyramids, 869, 875, 878
of sensory paths, 894
Defecation, 332
Deficiency diseases, 617, 632
phenomena after nervous lesions, 888
Degeneration of muscle, 804
of nerves, 795, 797
chemistry of, 798
of spinal roots, 797
reaction of, 804
Deglutition, 322
centre, 325
nerves of, 325
reflex, IOOO
sounds, 324
Deiters' nucleus, 884, 886, 893, 928
Delirium cordis, 151, 205
Demarcation current, 823, 842
electromotive force of, 826
theories of, 828
Dendrites, 852
amoeboid movements of, 852
and sleep, 986
Dentate nucleus, 863, 869, 886
of olive, 869
Depressor nerves, 170, 173, 185, 186
pressor action of, 188
reflex, reversal of, 904
in cerebral anaemia, 188
Descending degeneration, 866, 875
Deutero-proteose, 3, 10
Development of embryo, 1124
of ovum, 1 122
Dextrins, 3, n, 347, 455, 715
formed in salivary digestion, 347,455
tests for, 11,715
Dextrose, 3, 47, 338, 347, 455, 525. 534
537
estimation of, in urine, 525
in blood, 47, 50, 446, 499, 500, 540,
552
estimation of, 717
in lymph, 446
ratio to nitrogen in urine in diabetes,
55i
tests for, 10, 488
Trommer's test for, 10
Diabetes, 546, 55-2
dextrose-nitrogen ratio in, 55 1
diet in, 554, 556
mellitus, 552
oxygen consumption in, 242
pancreatic, 546, 554, 636
phlorhizin, 551, 717
reaction of blood in, 24
respiratory quotient in, 242
sugar-destroying power of blood in,
554
1226
INDEX
Diabetic coma, 555
Diapedesis, 61, 194
Diaphragm in respiration, 226, 228, 275
recording movements of, 233
Diastases, 87, 344, 370, 384, 534
Diastase, salivary, 344
Diastole of heart, 87
Dichromatic vision, 1060, 1112
Dicrotic wave of pulse, 104, 1 1 1
Dietaries, standard, 623, 625, 627
Dietetics, 622
Diet in diabetes, 554, 556
Diffusion, 426
circles, 1021, 1062
of gases, 246
through lungs, 264
Digestion as a whole, 416
and absorption, time required for,
464
bacteria and, 422, 423
changes in acidity of gastric contents
in, 418
chemical phenomena of, 336-374
comparative, 318
gaseous exchange during, 243
heat-production in, 713
in intestines, 418
in stomach, 416
mechanical phenomena of, 321
of carbo-hydrates, 356, 362, 416
of fats, 355, 363, 367, 461, 463, 464
of proteins, 351, 358, 417, 458, 460
significance of, 321
time required for, 418, 464
Digestive glands, microscopical changes,
374
juices, adaptation of, to food, 369,
398, 404, 410, 415
process of formation of, 383
protectipn of mucous mem-
brane from, 389
summary, 415, 416
organs in different animals, 318
Digitalis, diuretic action of, 509
Dilator of pupil, 1025
Diopter, 1021
Diphasic variations, 825
Diphtheria toxin, action of enzymes on,
372
Diplopia, 924, 1037
Direct cerebellar tract, 866, 872, 892
connections of, 872
' pyramidal tract, 866, 875, 878
Disaccharides, 3, 371
absorption of, 445
Discharge of ventricle, period of, 87, 97
Dispersion in eye, 1028
Dissociation of oxyhaemoglobin, 253, 273
Diuresis by salts, 509
Diuretics, 509
Double conduction in nerve, 792
Dromograph, 122
Dulcite, 3
Duodenum, digestion in, 417
glycosuria after removal of, 640
reaction of contents of, 419
Dura mater, 861
Dyspnoea, 283
heat, 283, 302
respiratory quotient in, 241
Ear, anatomy of, 1065
ossicles of, 1065, 1066
functions of, 1069
resonance tone of, 89, 760
Echidnase, 53
Eck's fistula, 385, 585
Ectoderm, 6, 1124
Ectoplasm, 4
Edestin, 607
tryptic digestion of, 361
Effector organs, 898
Efferent impulses, decussation of, 869,
875, 878, 893
paths of, 893
scheme of, 890
Egg-albumin, absorption of, 447
amino-acids in, i
excretion of, 448, 500, 716
reactions of, 9
Eggs, iron in, 622
Ehrlich's triacid stain, 1 7
Eighth nerve. See Auditory nerve
Elasticity of muscle, 735
Electric fishes, 840
signal, 732
Electrical conductivity of blood, 26, 68
of gastric juice, 387
of milk, 1139
of serum, 69, 386
organ, 841
response. See Action current
Electro-cardiogram, human, 835-838
Electrodes, to make, 808
unpolarizable, 731, 842
Electrolytes, 428
Electrometer, 727
capillary, 728, 729, 826, 842
Electromotive force, 725, 827
Electrons, 429
Electrotonic alterations of excitability
and conductivity, 786, 844
currents, 830, 844
Electrotonus, 785, 844
Eleventh nerve, 931
Emboli, artificial, 848
Embryo and uterus, connections be-
tween, 1126
asphyxia in, 1137
circulation in, 1126, 1138
development of, 1122, 1126
formation of the, 1124
gases of blood in, 1129
glycogen in, 538, 1131, 1133
INDEX
1227
Embryo, heat-production in, 1135
inverting enzymes in, 371
liver in, 1132
metabolism of, 1133
physiology of, 1128, 1129
Emetics, 336, 459, 464
Emmetropic eye, 1029
Emotions, genesis of, 974
Emulsincation, 12, 367
Emulsin, 338, 340
Endocardiac pressure, 92, 94
amount of, in ventricle, 92, 94
curves of, 93, 96, 97
measurement of, 93
negative, 101
Endocrine glands, 635
Endoderm, 6, 1125
Endo-enzymes, 337
Endogenous fibres of cord, 863, 867, 897
metabolism of proteins, 573
Endoplasm, 4
Endothermic reactions, 689
Enemata, 331, 451
Energy of food, influence of hydrolysis
on, 683
law of conservation of, in body, 679,
683
Engrafting, 641, 1142
Enterokinase, 372, 415
nature of, 373
Enzymes. See Ferments
Ependyma, 86 1
Epiblast. See Ectoderm
Epicritic sensibility, 1091
Epiglottis, 323
Epilepsy, cortical, 972
Jacksonian, 972
produced by absinthe, 964
Epinephrin, 66, 173, 655. See Adrenalin
function of, 657
indispensability of, 657
partition of, in blood, 659, 1149
secretion of, 66 1
testing for, 656
Equilibration and afferent impressions
from muscles, 941
from skin, 941
and orientation, afferent impulses
concerned in, 935, 936
cerebellum and, 934
Deiters' nucleus and, 929
in dog, 937
in dogfish, 938
in pigeon, 937
muscular nerves and, 941
postural reflexes and, 938
semicircular canals and, 928, 929,
936-941
skin and, 941
Erection centre, 183
Erepsin, 371
Ergograph, 642, 750, 752, 813
Ergot and blood-pressure, 173
Erucic acid, 556, 558
Erythroblasts, 21
Erythrocytes, 15. See Blood-corpuscles,
red
enumeration of, 19, 67
gases of, 250-257
life-history of, 20
Erythrodextrin, n, 347, 455, 715
Esbach's method of estimating albumin,
, S25
Eserihe, action of, on accommodation,
1022
on pupil, 1026
Ether, action of, on blood-corpuscles, 28,
29,70
Ethyl butyrate, synthesis of, by lipase,
338, 444
Eudiometer, 249
Euglobulin, 48
Eustachian tube, 297, 1065
valve, 1132
Evaporation, loss of heat by, 682
Excitability, a property of living matter, 7
and conductivity, voltaic current
and, 787, 844
-direct, of muscle, 738, 8ll
of nerve, effect of temperature on,
784, 790
electrical currents on, 758,
785,844
Excitable tissues, the, 724
Excretion, 475
Exogenous metabolism of proteins, 573
Exothermic reactions, 689
Expectoration, 475
Expiration, 226, 229
duration of, 234
forced, 230
Expired air, composition of, 239-241, 305
Extensibility of muscle, 736
Extension reflex, crossed, 902, 997, 998
Extensor thrust reflex, the, 901
Extero-ceptive reflexes, 914
Extra contraction of heart, 155
systoles, in man, 155, 156
Exudation, inflammatory, 61
Eye, action currents of, 839
artificial, Klihne's, 1104
chemistry of refractive media, 1016
compound of insects, 1013
defects of, 1027
development of, 850
dissection of, lioi
extrinsic muscles of, 1063
liquids, 1016
secretion of, 1016
movements of, 1062
nerves of, 1023, 1024
optical constants, 1017
pupillo-constrictor fibres, 1023,
dilator fibres, 1023, mo
1228
INDEX
Eye, reduced, 1019
refraction in, 1017
retinal fatigue, 1055, 1 1 12
structure of, 1014, IIOI
visual acuity, I III
Facial nerve, 926
union of, with accessory, 976
palsy, 926
Facilitation of reflexes, 909
in motor cortex, 954
Faeces, action of extracts of, 424
bacteria in, 424
composition of, 423
microscopical examination of, 463
odour of, 424
Fasting men, metabolism in, 604
hunger sensations in, 1096
Fat, absorption of, 441, 463
influenced by bile, 369
amount of, in standard diet, 623, 625,
627
chemistry of, 556
composition of, i
excretion of, into intestine, 443
formation of, from carbo-hydrates,
560
protein, 561
intermediary metabolism of, 565
melting-point of, 12
metabolism of, 556
liver and, 567
migration of, 557, 563, 568
in phosphorus poisoning, 563
mobilization of, 565
non-nutritive function of, 568
passage out of, intestinal epithelium,
442
storing of, 558
synthesis of, in intestinal mucosa?,
443i 444
Fatigue, changes in nerve cells, 859,
983
influence of, on muscular contrac-
tions, 749, 813
on muscle-curve, 813
muscular, cause of, 751
of muscle-nerve preparation, seat of
exhaustion in, 752, 813
seats of, in voluntary contraction,
753
Fats, constitution of, 3, 556
tests for, II
Fatty acids, absorption of, 443
and glycogen formation, 538
decomposition of, in body, 566
formation of, from carbo-hy-
drate, 561
synthesis of, to fat, 444
tests for, 12
Fechner's law, noo
Fehling's solution, 526
Fehling's solution, Benedict's modifica-
tion of, 527
test for sugar, 525
Ferment action, quantitative estimation
of, 342, 453
cellulose-dissolving, 423
mode of action of, 339, 341
reversible action of, 339
Fermentation, butyric acid, 423
lactic acid, 423
Ferments, 336
autolytic, 599
in the liver, %>o
intracellular, 337
list of, 345
specificity of, 340
Fever, aseptic, 707
caused by cocain, 704
by xanthin, 707
changes in urine in, 703
derangement of heat regulation in,
705
metabolism in, 706
nervous, 708
production of heat in, 704
' puncture," 701
' retention theory,' 706
significance of, 708
vaso-motors in, 706
Fibrillary contraction, 151, 205
Fibrin-ferment, 34. See Throinbin
formation of, 35
preparation of, 65
Fibrinogen, 34
production of, in liver, 35
Fibrino-globulin, 47
Pick's theory of fusion of visual stimuli,
1050
Fillet, 874, 881 '
Flavour, 1078
Flechsig's developmental cortical zones,
961
Flexion reflex, 903, 997
Flour, 719
Flow of liquids, with intermittent pres-
sure, 85
Fluoride plasma, clotting of, 38 .
Fluorides, action of, on coagulation,
37,64
Foetal heart, 1135
Folin's method of estimating ammonia.
521
creatinin, 524
indican, 518
uric acid, 523
Food substances, 320
Foods, isodynamic relations of, 773
specific dynamic action of, 686
Foramen of Monro, 850
Forced movements, 944
Fore brain, 850
Formaldehvde reaction for proteins, 8
INDEX
1229
Formatio reticularis, 870
Formic acid, 556
Formula of contraction. See Law of
contraction, 845
Freezing-point, determination of, 529
Frey's aesthesiometer, 1080
Frog, heart of, anatomy, 194
to pith a, 193
vagus, dissection of, 196
stimulation of, 198
web of, circulation in, 193
Function, localization of, in cortex, 975
Fundus of stomach, 326
Funiculus cuneatus, 869
gracilis, 869
Gall-bladder, 411, 419
reflex contraction of, 412
Gall-stone, pain caused by, 901
Galvani's experiment, 822, 842
Galvanometers, 726
string, 727, 836
Ganglia habenulae, 933
of posterior roots, development of,
850
Ganglion cells, sympathetic, 856
spirale, 927
vestibulare, 927
Gaskell's method (heart), 195
Gas-pump, 249
Gaseous exchange in lungs, mechanism
of, 263
Gases, absorption coefficient of, 247
diffusion of, 246
of blood, 245
extraction of, 249
quantity of, 250
tension of, 258
of muscle, 268, 269
partial pressure of, 247
tension of, 248
in tissues, 267
Gasserian ganglion, development of, 854
Gastric digestion, role of HC1 in, 353
testing for products of, 458
glands, influence of nerves on, 401
secretory changes in, 378-381
juice, 349
acidity of, 350
antiseptic function of, 356
artificial, 458
Beaumont's work on, 349
chemistry of, 350
digestion of proteins by, 351,
458
electrical conductivity of, 387
freezing-point of, 387
hydrochloric acid of, 350
in cancer, 350
influence of substances on se-
cretion of, 403, 405
lactic acid in, 351
Gastric juice, milk-curdling action of,
353
psychical secretion of, 404
to obtain pure, 459
secretion, 401
Gelatin as a food, 614
from nerves, 795
tests for, 9
Geminal fibres, 879
Gemmules, 852
Geniculate bodies, 923
Giant pyramids of Betz, 959
Gianuzzi, crescents of, 375
Gibbs, thennodynamic law, 431
Glands, action currents of, 838
heat-production in, 689
Gliadin, feeding with, 617
Globin, 54
Globulins, tests for, 9
Glomerulus, function of, 492, 493, 495,
497, 505
Glosso-pharyngeal nerve, 929
and taste, 925
Glottis, in voice production, 308, 312
Gluco-proteins, 2
Glucose, 10. See Dextrose
Glufamic or glutaminic acid, 360, 575
Glycerine, i, 363, 366, 536, 556
formation of, from carbo-hydrates,
56i
of glycogen from, 536
tests for, 12
Glycerose, 537
Glyceryl-phosphoric acid, 366, 421, 571
Glycin or glycocoll, i, 360, 576, 580, 581
Glycocholic acid, 365
Glycogen, 3, 523
and lactic acid, production in mus-
cle, 771
as reserve material, 539
extra hepatic, 538
formation of, from protein, 535, 538
formers, 536
function and fate of, 539
in liver, 534
in liver capillaries, 535
in muscle, 767, 768
preparation of, 715
Glycogenase, 600
Glycogenolytic nerve fibres, 549
Glycolysis, 540
pancreas and, 545
Gly conic acid, 543
Glycosuria, after injection of sugar into
the blood, 716
adrenalin, 550
alimentary, 540, 717
caused by drugs, 552
phlorhizin, 551, 717
produced by asphyxia, 548
puncture, 547
relation of adrenals to, 548
1230
INDEX
Glycuronic acid, 47, 482, 526, 543
Glyoxal (methyl-), conversion into lactic
acid, 545
Goitre, exophthalmic, 650
of brook trout, 649
Golgi's method, 851
Goll, column of, 865, 866
connections of, 870
Gout, 487, 590
Gowers, tract of, 866
Graafian follicles in ovarian grafts, 641
Gracile funiculus, 869
Gracilis experiment of Kiihne, 913
Grafting tissues, 641, 1142
Gramme-molecular weight, 426
' Granule-cell,' 856
Ground bundles of cord, 867
Growth, foods adequate for, 614-618
Guaiconic acid and oxydases, 272
Guaiacum test for blood, 76, 272
Guanidin and parathyroid, 647
Guanin, 592, 593
Gudernatsch on influence of thyroid on
tadpoles, 653
Giinzburg's reagent for hydrochloric acid,
460
Gymnotus, 841
Gyrus postcentralis, stimulation of, 963
precentralis, 963
Hasmatachometer, 121
Haematin, 54
acid, 54, 75
alkaline, 54, 75
Haematocrite, 27, 68
Haematoidin, 385
Haematopoiesis, 20
Hasmatoporphyrin, 55, 76
in urine, 483
Haemin, 55,79
Haemochromogen, 54, 76
Haemoglobin, composition of, 50
crystallization of, 52
crystals, preparation of, 73
curves of dissociation, 253-255
influence of carbon dioxide on, 255
intracorpuscular crystallization of,
52
quantitative estimation of, 76
spectroscope examination of, 74
spectrum of, 51, 53
Haemoglobinometer, 76
Ha'inoglobinuria, paroxysmal, 483
Haemolysis, 28, 71
by foreign serum, 71
mechanism of, 29
Haemometer, 77
Haemophilia, coagulation in, 45
Haemorrhage and transfusion, influence
of, on blood-pressure, 191 , 214
quantity of blood which may be
lost in, 191
Hair-cells of internal ear, 937
Haldane's apparatus for CO;, 304
for H2O and CO2, 305
Harmonics, 310
Hay's test for bile-salts, 528
Head, transplanting of, 975
Hearing, 1064
analysis of complex sounds, 1072
beats, 1113
cranial conduction of sound, 1071,
IH3
monochord, 1113
perception of pitch, 1073
range of, 1075
sympathetic vibration, 313, 1113
theories of, 1074
Heart, action current of, 833, 844
' all or nothing ' law of, 154
apex, preparation of, 194
arrangement of fibres in, 78
augmentor nerves of, 157, 162, 165,
168, 198
auricular flutter, 151
automatism of, 142
beat, 85, 194, 201
cause of, 141
chemical conditions of, 152
neurogenic and myogenic hypo-
thesis of, 142
standstill, action of augmentor
nerves in, 168
conduction and co-ordination in,
146
conductivity of, 142
excitability of, 142
extra systoles of, 155
extrinsic nerves of, 156
' fractionate ' contraction of, 163
ganglion cells of, 141, 165
impulse of, 90
inhibitory nerves of, 157, 162, 164,
198, 203, 212
inhibition of, 156, 167
intrinsic nerves of, 141, 157
muscle, action of inorganic salts on,
198
of Limulus, 143
output of, 139
pacemaker of, 143
pause of, 97
perfusion of, 153, 205
pressure in, variations of, 97
refractory period ano*e~xtra contrac-
tion of, 155 «^
resuscitation of, 153
rhythmicity of, 142
sounds of, 88, 207, 837
source of energy of contraction of,
772
suction action of, 101
temperature in, 710
tonicitv of, 142
INDEX
1231
Heart tracings, 164, 171, 194, 203, 837
simultaneous, from auricle and
ventricle, 160, 161, 196
valves of, 86, 204, 206
work done by, 138
Heat centres, 701
coagulation, 9, 819
distribution of, 709
equivalents of food substances,
684
given off in respiration, measure-
ment of, 682, 721
liberated in cleavage of food sub-
stances, 683
loss, 681
regulation of, involuntary, 690
voluntary, 692
production, amount of, 683
and work, 684
effect of curara on, 694
in brain, 689
in digestion, 686, 713
in fever, 704
in glands, 689
in heart, 688
in muscles, 687
in rigor, 778
of different classes of workers,
685, 687
relation of, to muscular work,
764, 765
regulation of, involuntary, 693
voluntary, 692
seats of, 686
surface and blood- flow relations,
696
rigor. See Rigor, heat, 777, 820
sources of, in body, 683
standstill of heart, 159, 194
Heller's test for albumin, 524
Helmholtz's theory (vision), 1053
(vowel sounds), 314
(pitch perception), 1073
Hemeralopia, 1060
Hemianaesthesia, capsular, 88 1
Hemianopia, 923, 965
Hemibilirubin, 365
Hemiplegia, reflexes in, 911
Bering's theory of colour vision, 1057
Herpes zoster and trophic nerves, 806
Hexoses, 3, 537
Hibernating animals, temperature regu-
lation in, 703
respiratory quotient in, 241
Hiccup, 288
Hippuric acid, 524, 580, 614
formation, 580
Hirudin and coagulation, 37 '
Histidin, 54, 360
Histones, 2
Holmgren's wools, 1112
Homogentisinic acid, 483, 525
Homoiothermal animals, production of
carbon dioxide in, 244
thermotaxis in, 690
Homo-lateral fibres, 879
Homologous stimuli, 1007
Hormones, 404
Humidity of air and heat regulation, 691
Hunger sensation, 930, 1096
Hydraemic plethora, 462, 500
Hydrocele fluid, 39
coagulation of, 35
Hydrochloric acid in gastric juice, 350
formation of, 379, 380
Hydrogen, income and expenditure of,
6rg
Hydrogen ion concentration of blood,
24
and respiratory centre, 282
of duodenal contents, 419
of gastric contents, 420
of milk, 1139
Hydrolysis, 2
Hydros tomia, 401
Hyoscyamine, action of, on pupil, 1026
Hyperglycaemia, 500, 540
adrenalin, 550
alimentary, 540
asphyxia, 548
in diabetes, 552
pancreatic, 546, 636
puncture, 547
relation of adrenal to 548
Hyperisotonic solutions, 428
Hypermetropia, 1030
Hyperpncea, 283
Hypoglossal nerve, 931
Hypoisotonic solutions, 428
Hypophysin, 668
Hypophysis. See Pituitary body
Hypoxanthin, 589, 592, 593
Identical points, theory of, 1037
Idio-muscular contraction, 759
Ileo-caecal valve, 331
colic sphincter, 331
Illusions, optical, 1041
Imbibition, 426
Indican, 484, 517
estimation of, 518
Indol, formation of, in intestine, 422
Indophenyloxydase, 272
Induction machine, arranged for tetanus,
2OO
arranged for single shocks, 808
Inductorium, 730
Infundibulum, infundibular body, 666,
933
Inhibition from the cortex, 954
in reflex action, 903
nature of, 167
of heart, 156
Inorganic salts. See Salts
1232
INDEX
Inosinic acid, 767
Inosit, 767
Inspiration, 226
forced, 230
muscles of, 226, 227
Intellectual processes, seat of, 973
Intelligence, size of brain and, 988
Intermedio-lateral tract, 864, 865
Internal capsule, 88 1
frontal fibres in, 882
occipito-temporal fibres in, 882
respiration, 265
secretion of adrenal, 655
of kidney, 671
of ovaries, 641
of pancreas, 636
of parathyroid, 646
of pituitary body, 666
of pineal gland, 671
of spleen, 672
of testicles, 640
of thymus, 643
of thyroid, 645, 6^7
Intestinal epithelium, permeability of,
437
juice, adaptation of, to food, 415
collection of, 370
composition of, 371
influence of nerves on, 414
segments, effect of blood-serum on
contractions of, 453
action of epinephrin on, 453, 657
658
Intestine, large, absorption in, 422, 451
movements of, 330
Intestines, absorption of water in, 421
contraction of isolated, 452, 330
digestion in, 418
movements of, 328
nerves of, 331, 332
reaction of contents of, 419, 420
resection of, 451
Intraocular tension, 1017
Intrathoracic pressure, 236, 237
Invertase, 338, 339
in intestinal juice, 371
Inversion of carbo-hydrates, 356
Iodine, influence of, on thyroid, 650-654
Ions, 429
Iris, effect of stimulation of sympathetic
on, 1023, mo
functions of, 1026
in accommodation, 1023
local mechanism of, 1025
nerves of, 1023
Iron, absorption of, 447
in eggs, 622
jn liver cells, 463
in milk, 622
Irradiation, 1061
Island of Reil, 973
Islets of Langerhans, 638
Isodynamic relation of food substances
773
Isomaltose, 338
Isotonic and isometric contraction, 747
solutions, 428
Itching, sensation of, 1085
Jacksonian epilepsy, 972
Japanese dancing mice, labyrinth of, 945
Jaundice, 384, 414
colour of stools in, 369
haematogenic, 385
Jaw-jerk, 915
Karyokinesis, 5
Karyosome. See Nucleolus
Katabolism. See Metabolism
Kephalin, 42, 571, 794, 991-
Ketohexoses, 537
Ketones, 537
Kidney, bloodvessels and tubules of,
489
excretion of pigments by, 495
formation of hippuric acid in, 580
gas exchange of, 266, 504
internal secretion of, 671
nerves of, 504
tubules of, 490, 492
Kinaesthetic area, 963
Knee-jerk, 904, 915
reinforcement of, 911
Kreatin and kreatinin. See Creatin and
Creatinin
Kiihne's artificial eye, 1104
Labyrinth, 927, 1067
and equilibration, 936, 938
and postural reflexes, 918
Laccase, 272, 337
Lachrymal glands, 475
Lactalbumin, 719
Lactase, 338, 340, 371, 410
Lacteals, 463
absorption of fat by, 443
Lactic acid and heat-production in
muscle, 767
as stage in decomposition of,
dextrose, 543
fermentation, 423
formation of, in muscle, 769
Hopkins's reaction for, 821
in metabolism, 544, 545
in nervous tissue, 795
in stomach, 350
precursor of, in muscle, 770
Uffelmann's test for, 460
Laking, of blood, 28. See Haemolysis
Landergren's hypothesis, 551
Langerhans, islets of, 638
Lanolin, and fat absorption, 442
Larynx, action of muscles of, 308
and voice production, 307
1*33
Latent period of muscular contraction,
745,815
L teral ground-bundle, 867
nucleus of bulb, 873
Law of contraction, 788, 845
Lecithin, i, 47, 366, 571, 794, 991
digestion of, 421
Leclanche battery, 198
Leech extract and coagulation, 38
Left-handed people, aphasia in, 971
Legal's test for acetone, 529
Leucin, 360, 461, 488
Leucocytes, chemistry of, 55
eosinophile, 17
number of, 19
origin of, 22
polymorphonuclear, 17
transitional, 17
varieties of, 17
Leucocytosis, 19
Leukaemia, 19
Levatores costarum, action of, in respira-
tion, 227
Levulose, 356, 538
formation of glycogen from, 537
Lieben's test for acetone, 529
Lieberkiihn's crypts, 370, 374, 375
functions of, 45 1
Lime salts, deficiency of, changes caused
by, 621
Limulus heart, 143
Linolic acid, 556
Lipase, 48, 338
gastric, 355
pancreatic, 363
reversible action of, 338, 444
Lipoids, i, 3
Lipoid-solubility of absorbed substances,
437
Liquids, flow of, 83
Lissauer, tract of, 866
Listing's law, 1063
Liver and amino-acids, 584
and coagulation, 44
and deamidization, 588
and glycogen formation, 533, 535
and metabolism of fat, 567
and urea formation, 584 •
cells, iron in, 385, 463
temperature, 689, 712
Living matter, chemical composition
"of, i
functions of , 6 '
structure of, 4
Living test-tube experiment, 34
Localization in different animals, 980
of function jn cortex, 97$
Locomotion, 946
Locomotor- ataxia, disappearance of
knee-jerk in, 915
Lungs, area of, 224
auscultation of, 231, 304
Lung ;, blood-supply of, 223
circulation time of, 224
mechanism of gas exchange in, 263
quantity of blood in, 224
Lymph, composition of, 57
different kinds of, 466
flow, factors in, 192
formation, and activity of organs,
472
factors concerned in, 467
influence of nerves on, 473
freezing-point of, 473
hearts, 192, 193
post-mortem flow of, 474
pressure of, 192
rate of flow of, 192 :
Lymphagogues, 468
Lymphatic circulation, 192
glands, 192
Lymphatics, valves of, 192
Lymphoblasts, 22
Lymphocytes, 17
Lysin, 360
synthesis of, in body, 614
Macula hitea, 975, 1107
Magendie-Bell law, 891
Make and break shocks, 807
Malapterurus electricus, 840
nerve of electrical organ, 850 '
Maltase, 340, 345
in intestinal juice, 371
Maltose, absorption of, 445
Mammary glands, fat formation in, 565,
1141
line, 90
Manganese salts and coagulation, 37
Mannite, 3
Manometer, 92
differential, 96
Hiirthle's elastic, 93
maximum and minimum, 92
optical, 93
with side-tube, 212
Marchi' staining reaction, 797
Marginal veil, 850, 858
Marie, tract of, 867
Mariotte's experiment, 1044, 1107
Mast cells, 18
Mastication, 321
Mate, 632
Maxwell's spot (vision), 1107
Meconium, 424
Mediastinum, 225 ' . ,\<
Medulla oblongata,- structure of, 869
' Medullary ' groove, 849
sheath, development 'of, 959
Megakaryocytes, 18 .-,.-.'
Megaloblasts, 21
Meissner's plexus, 320 . •
Menitre's disease, 940
Menstruation, 1120
78
I2J4
INDEX
Mcrcapturic acid, 581
Mcscnccphalon, 850
Metabolism, 6
basal, 686
in fever, 706
in starvation, 602
intermediary, of carbo-hydrates, 542
of fat, 565
of amino-acids, 582
of nucleic acids and puriu bases, 592
of phosphatides, 571
of proteins, 572
and muscular work, 610
in starvation, 603
of sterins, 570
relation of, to surface, 695, 696
Meta-proteins, 3
Metencephalon, 850
Methaemoglobin, 53, 75
Methylene blue, behaviour of, in tissues,
137,218,956
Methylglyoxal, 545
Methyl orange as indicator, $22
Metronome, 195
Mett's tubes, 343, 454
Microblasts, 21
Microtonometer, 259
Micturition, 5*0
centre, 511, 9*5, 920
Milk, 1135
as a food, 62 1
chemistry of, 629, 718, 1139
clotting of, 353,719
. digestion of, 353, 417
hydrogen ion concentration of, 1139
secretion of, 1140
Millqn's reagent, 8
Mitosis, 5
Mitral valve, 86, 96
Moist chamber, 809, 843
Molecular concentration, 426
Molisch's test for carbo-hydrates, n
Monakow's tract, 867
Monochord, 1113
Monosaccharides, absorption of, 445
formation of glycogen from, 537
Monro, foramen of, 850
Morphine, quantity of, for dogs, 63
Morphology of the blood, 14
Motor aphasia, 9/0
' Motor ' areas, 951
Mountain sickness, 298
Movements, forced, 944
Mucin in bile, 364, 462
. in saliva, 344, 454
Mucous glands, secretory changes in, 381
Miiller's experiment, 296
Muscarine, action of, on heart, 164, 199
Muscle, action of curara on, 738, 8ll
action of nicotine on, 739
anaerobic contraction of, 269, 306,
770
Muscle, arrangement for tracings 812
chemistry of, 767, 819
composition of, 767
contraction of, 743
theories of, 744
influence of load on, 747, 813
of temperature on, 749, 813
degeneration of, 804
diffraction spectrum, 745
direct excitability of, 738, 8n
direct stimulation of, 740
efficiency of, 765
elasticity of, 736
extensibility of, 736
fatigue of, 749, 813
cause of, 751
seats of, 752, 753' 813
formation of lactic acid in, 751, 769
820
gases of, 270
general physiology of, 723
heat-production in, 686, 762, 764
' idio-muscular ' contraction of,
759
nerve preparation, 808
fatigue of, 752, 813
of eyes, extrinsic, 1063
oxygen consumption of, 269
permeability of, 773
physical properties of, 735
reaction of, 769, 820
receptive substances of, 739
respiration of, 269
smooth, contraction of, 745, 747, 817
wave of contraction in, 759
spindles, 804
stimulation, 737
structure of, 742
trough, 809
Muscular contraction and lactic acid, 767,
770
changes during, 744
chemical phenomena of, 767
CO2 production in, 270, 768
duration of, 745
graphic record of, 8ll
heat-production in, 762, 763
in absence of oxygen, 269, 306,
770
influence of fatigue, 749, 812
of load on, 747, 813
of mental fatigue on, 754
of previous stimulation < n,
749, 813
of temperature on, 749,
813
of veratrine, on 754, 814
isotonic and isometric, 747
latent period of, 7^, 815
mechanical phe/t«mena of, 745
optical phenomena of, 742
oxygen consumption in', 768
INDEX
1235
Muscular contraction, physico-chemical
conditions of, 773
rate of wave of, 759
relation between mechanical
energy and heat-production,
765
relation of glycogeu to, 771
substances metabolized in, 771
superposition of, 756, 816
theories of, 744
time relations of, 747
voluntary, 760
work done in, 747
sensations, 1094
tissue, action of extracts of, 673
tone, 917, 938, 1000
work and nitrogenous metabolism,
610
source of energy of, 611, 767,
771
Musical centres, 967
Myelencephalon, 850
Myelin sheath, fragmentation of, 796
Myelination of tracts at different times,
961
Myeloblasts, 22
Myocardiograph, 162, 203
Myograph, 195, 745, 812
spring, 746, 815
Myohaematin, 767
Myosin, 820
Myosinogen, 820
Myxoedema, 648
Negative variation. See Action current
Nerve, carbon dioxide production in,
782
chemical changes in, 782
chemistry of, 794
conductivity of, 790
anaesthetics and, 814
degeneration of, 795
phosphorus in, 797
endings, action of drugs on, 182
excitability of, 784
and conductivity of, 786
fibres, medullated, 781, 860
structure of, 781, 851
heat-production in, 782
impulse, nature of, 781
velocity of, 793, 818
temperature coefficient of,
782
muscle preparation, 808
pattern of, 799
polarization of, 829
propagated disturbance of, 781
regeneration of, 798
autogenetic, 802
chemiotaxis in, 800
stimulation of, 783
trunks, cooling of, 979
Nerves, anastomosis of, 798, 976
classification of, 807
posterior roots, section of, 797, 964
preganglionic, 185, 865
specific energy of, 979
trophic, 805
Nerve-cells, growth in vitro, 802, 803, 856,
857
effect of anaemia on, 859
anaesthetics on, 859
division of axons on, 795, 859
fatigue on, 859, 983, 984
of Golgi's second type, 856
Nervi erigentes, 180, 332, 334
Nervous activity, chemistry of, 782, 795,
991
Nervous system, autonomic, 1003
development of, in different
animals, 898
tissue, action of extracts of, 673
Neural canal, 849
groove, 849
Neuroblasts, 849, 858
Neuroglia, 86 1
Neurokeratin, 795
Neurons, 851
growth of, 857
nutrition of, 858
scheme of lower motor, 855
varieties of, 855, 856
Nicotine, action of, on ganglion cells of
heart, 166
on skeletal muscle, 740
on sympathetic, 182, 1005
effect of, on nerve-cells, 182, 913
Night-blindness, 1060
Nissl substance, 851, 984
Nitrogen balance-sheet, 602
necessary quantity of, in diet, 623,
624, 625
total, estimation of, 521
variation of, with protein in
food, 720
Nitrogenous equilibrium, 602
protein necessary for, 605
metabolism and muscular work,
610
Norleucin, 360
Normal solution, 479
Normoblasts, 21
Nuclease, 594
Nucleic acids, chemistry of, 593
metabolism of, 592
Nucleo-proteins, i, 2, 47
digestion of, 417, 592
Nucleosides, synthesis of, 597
Nucleotidase, 594
Nucleotids, 593
Nucleus, 5
globosus, 885
importance of, for cell, 795
tecti, 885, 928
1236
INDEX
Oatmeal as a food, 626
in diabetes, 555
Obesity, 568
Banting cure for, 606
treatment of, 570
Occipital lesions, 966
Oculo-motor nerve, 924, 982, 1023
Odours, classification of, 1076
(Esophagus, contractions of, 323, 817
pulse, 99
Ohm's law, 725
Oleic acid, 556
Olein, 4
Olfactometer, 1076
Olfactory bulb, 922
nerve, 921
Olivo-spinal tract, 867, 885
Oncometer, 507
Oophorin, 642
Ophthalmometer, 1021, 1 105
Ophthalmoscope, 1031, II08
Geneva, 1 1 10
Opsonins, 61
Optical illusions, 1041
Optic lobes, 932
and inhibition of reflexes, 910,
996
nerve, 922
radiation, 883, 923
thalamus, 883, 932
Orcin reaction for pentoses, 528
Orientation, mechanism of, 936
Ornithin, 587, 613
Osmosis, 426
and diffusion, in lymph formation,
47i
Osmotic pressure, 426
resistance of coloured corpuscles, 73
Ossicles, auditory, 1066, 1069
Otoliths, 937
Output of heart, 139
Ovaries, internal secretion of, 641
Ovary, influence on metabolism, 642
Overtones, 310, 313
Ovum, development of the, 1122
Oxalates, action of, on coagulation, 37, 64
in urinary sediments, 478, 532
Oxalic acid, 481
Oxidation, seats of, 265
Oxidative process, nature of, 271
Oxidizing ferments or oxydases, 271, 272,
306
Oxybutyric acid, 555, 562, 567
Oxydases, 48, 76, 271, 306
Oxygen absorption, mechanism of, 263
capacity of blood, 251
coefficient of utilization of, 697
consumption of, 242, 243
in different animals, 245
of different tissues, 268, 271
deficit, 620
distribution of, in blood, 252
Oxygen, income and expenditure of, 619
partial pressure of, in alveoli, 241
261, 263
passage from blood into tissues, 266
tension in blood, 258, 261, 262
Oxyntic cells, 375, 378, 380
Oxyprolin, 360
Pain, in internal organs, 901, 1093
referred, 891
sensations, 1085, 1089, 1116
paths for, 896
Pancreas and glycolysis, 546
and spleen, mutual relations of, 411
influence of nerves on, 405, 407
internal secretion, 636
islet tissue of, 638
removal of, in pregnancy, 638
secretory changes in, 376
Pancreatic diabetes, 546, 636
juice, adaptation of, to lactose, 410
and bile, adjuvant action of,
367, 368
artificial, 460
composition of, 358
ferments of, 358-363, 460
freezing-point of, 386
rate of secretion of, 410
secretion, influence of food on,
409
Panniculus adiposus, 568
Parabiosis, 638, 1146
Paradoxical contraction, 832, 844
Paraglobulin, 48
' Paralytic ' secretion of intestinal juice,
414
of saliva, 397
Paraphasia, 972
Parasternal line, 90
Parathyroid, effects of removal of, 646
location of, 645
Parenteral absorption of proteins, 33
Parotid, secretory changes in, 375, 376
Paroxysmal tachycardia, electro-cardio-
gram, 836
Parthenogenesis, 1123
Partial pressure of gases, 248
Parturition, 1137
Peduncle, inferior, of cerebellum, 885
Pellagra and vitamines, 632
Pelvic nerves, 179, 332
Pendulum movements of intestines, 328
Pengavar Djambi as styptic, 1001
Pentoses, 528, 593
Pentosuria, 487
Peptases, 361
Peptides, 2
Peptones and coagulation, 37
tests for, 10
Percussion, 232
Perfusion of heart, 205
Perikaryon, 850
INDEX
1237
Perimetry, 1048
Periodic breathing, production of, 287,
300
Peripheral reflex centres, 912
Peristalsis, 324, 326, 329, 330
Peritoneal cavity, absorption from, 439
Peroxydase, 76
Persistence theory (vision) 1050
Perspiration, visible and invisible, 512
Pettenkofer's test for bile acids, 366, 462
Phagocytosis, 59
Phakoscope, Helmholtz's, 1021, 1103
Phenol, excretion in starvation, 604
Phenyl-alanin, 2, 352, 360
Phenyl-hydrazine test for sugar, 525
Phlebogram, 101
Phlorhizin glycosuria, 551, 717
Phloroglucin reaction for pentoses, 528
Phosphocarnic acid, 767
Phosphates, estimation of, 516
Phosphate triple, sediments, 479, 531
Phosphatides, 571, 794
digestion of, 421
metabolism of, 571
synthesis of, 597, 607
Phospho-proteins, 2
Phosphorus in degenerated nerve, 797,
798
in milk, 621
poisoning and fat migration, 563
Photo-electric reaction of eye, 839
Phrenic nerves and respiration, 275
afferent fibres in, 284
anastomosis of, with sympa-
thetic, 801
Phytosterins, 366, 570
Pia mater, 861
Pilocarpine, action of, on nerve-endings,
182
effect of, on heart, 166, 199
on salivary secretion, 457
on pupil, 1026
Pilo-motor nerves, 180, 913, 1004
Pineal gland, 671, 933
Piotrowski's test, 8
Piston recorder, 233
Pitch, 310
Pithing a frog, 193
Pitot's tubes, 121
Pituitary body, 666, 933
action of extracts of, 668
functions of, 6/0
removal of, 667
Pituitrin, testing for, 670
Placenta, exchange of materials in, 1129
Plantar reflex, 915
Plasma, proteins of, 49
Plasmine of Denis, 34
Plasmolysis, 428
Platelets and coagulation, 37
Plethysmograph, 128
Plethysmographic tracings, 129, 210
Pleural cannula, 234
Poikilothermal animals, production of
carbon dioxide in, 244
heat in, 693
Poiseuille's laws of flow, 85
space, 15, 193
Polar stimulation, law of, 741
Polarimeter, 528
Polarization of muscle and nerve, 829
Polygraph, 103
tracings, 209
Polymorphonuclear leucocytes, 17
Polypeptides, 2, 352, 361, 578
Polysaccharides, 3, 347, 348, 535, 537
Pons, 932
connections of, 883
grey matter of, 883
Post-central gyrus, 963
Posterior longitudinal bundle, 885
Posterior root ganglia, development of,
850
Post-sphygmic interval of heart, 97
Postural reflexes, 917, 1000
Potassium in muscle, 767
salts, influence of, on heart-beat, 153,
200
Potential, electrical, 735
Precentral gyrus, 963
Precipitins, 31
Prepyramidal tract, 867
Presphygmic interval of heart, 97
Pressor nerves, 173
bases, 672
Pressure sensations, 1041, 1081, 1114
blood-, measurement of arterial, 109-
112, 2IO
in man, 113-116, 213
influence of exercise, 115
Primary colours, 1053
Prisms, 1010
Proferment, 343, 351, 358, 376, 382
Prolamins, 615
Prolin, 352, 360
Propionic acid, 556
transformation into dextrosej
538
Proprio-ceptive fields, 914
spinal fibres, 868
Pro-secretin, 408
Protamins, 2
and coagulation, 44
Proteins, i
absorption of, 447
' building stones ' of, 576
cleavage of, and absorption, 448
products of, 360
colour reactions of, 8
complete and incomplete, 613
consumption determined by supply,
607
digestion of, 351, 359, 361, 370, 417
formaldehyde reaction, 8
123*
INDEX
Proteins, formation of glycogen from, 536
of sugar from, 538
general reactions of, 7
Heller's test for, 524
in nutrition, relative value of dif-
ferent, 612
living and dead, 576
metabolism of, 572
necessary amount of, 623, 624
of tissues, specificity of, 321, 575
parenteral absorption of, 33
precipitation reactions of, 8
specific dynamic action of, 686
synthesis of, 573, 612
temperature of coagulation, 9
Protein-sparing action of fat, 606
of carbo-hydrates, 606
Proteoses, 3
action of, on coagulation, 37, 63
on clotting, 44
(and peptones), influence on blood-
pressure, 173, 215
formed in gastric digestion, 352, 458
action of erepsin on, 371
of trypsin on, 362
in blood and tissues, 574
in urine, 489, 525
secondary', 13
tests for, 10
Prothrombin, 36
Protoplasm, structure of, 4
Prozymogen, 343, 351, 358, 382
granules, 376
Pseudo-globulin, 49
-podia, 17
reflexes, 904
Psychical secretion, 399, 404, 1099
Ptyalin, 346, 416, 455
' Puberty gland,' 642
Pulmonary catheter, 259
circulation, 223
ventilation, 235
regulation of, 281
Pulse, anacrotic, 106
arterial, 101
curve, variation in form of, ijofr
effect of amyl-nitrite, 208
exercise on, 208
frequency of, 107, 210
tracings, 103, 209
venous, 99, 100, 101, 131, 209
wave, rate of propagation of, 108
Pulsus altemans, 155
bigeminus, 155
Pulvinar, 923, 933
' Puncture ' fever, 701
glycosuria, 547
Pupillo-dilator fibres, 1023, 1025, I no
Purin bases in urine, 481
metabolism of, 592
bodies, chemistry of, 593
excretion of, 594
Purkinje fibres of heart, 147
Purkinje's figures, 1042, 1113
Putrefaction in intestine, 422, 588
of proteins, action of products of,
672
Pyloric sphincter, relaxation of, 327, 418
Pyramidal cells, 853, 875, 958, 959
development of, 854
path in internal capsule, 878, 882
tracts, 866
connections of, 875
in different animals, 877
Pyramids, decussation of, 869, 875, 878
Pyrimidin bases, 593, 595, 597
Pyruvic acid, 544, 545, 546
Quadratus lumborum, action of, in
respiration, 227
Radiation from the skin, 68 1, 683
Radiometer, 681
Raffinose, 340
Rarefied air, effects of breathing, 295, 298
Rations, soldiers', 623, 627
Reaction of blood, 24
of degeneration, 804
of gastric juice, 420
of intestinal contents, 419
of milk, 1139
of urine, 479
' Receptive ' substances, 182, 739
Receptor in reflex action, role of, 900
Receptors, 898
Reciprocal relation of vasomotors, 186
Recurrent sensibility, 892
Referred pain, 891
Reflex action, anatomical basis of, 898
extensor thrust, 904
flexioTr, 903, 904, 997
inhibition in, 903
irradiation of, 905
of spinal cord, 897
scratch, 901, 902, 997
arc, fatigue~of, 902
isolated conduction of impulses
\ in, 899
peculiarities of conduction in,
902
properties of, 902
refractory state in, 9.03
cardiac death, 171
centres in cord, 915
peripheral, 912
inhibition of heart, 170, 210
time, 914
Reflexes, axon, 803, 913
common path of, 899
co-ordination of, 908
effect of strychnine on, 899
tetanus toxin on, 899
facilitation of, 909
in disease, 914
INDEX
1239
Reflexes, influence of brain on spinal, 910,
996
in hemiplegia, 911
inhibition of antagonistic, 910
long spinal, 907
postural, 917, 1000
reinforcement of, 911, 998
reversal of, 1^8, 903, 904
role of the receptor in, 900
short spinal, 906
simultaneous, combination of, 908
successive combinations of, 908, 909
superficial, 914
vado-motor, 185, 212
Refractory period of heart, 155
Regeneration, of nerves, 798
autogenetic theory, 801
bifurcation of axons in, 802
of tissues, 1117
Reil, island of, 973
Renal calculus, pain caused by, .901
Rennin, 353, 459, 719
function of, 354
Reproduction, 1117
in higher animals, 1118
Reserve air, 236, 303
Resistance, electrical, 724
measurement of, 725
of blood, 26,68
Resonance, 232, 310, 314
Respiration, accessory phenomena of, 231
afferent nerves of, 276, 300
and blood-pressure, in, 289
and nervous system, 274
artificial, 202, 230
by insufflation of oxygen, 204,
236
influence of, on blood-pressure,
292
breaking-point in, 234
calorimeter, 240, 676
chemical regulation of, 281
chemistry of, 239
comparative, 222
cutaneous, 299
efferent nerves of, 274
external, 225
forced, influence on carbon dioxide
excretion, 234, 245, 282, 283, 300
frequency of, 234
heat given off in, 681, 682, 683, 721
in condensed and rarefied air, 295
influence of cutaneous nerves on, 280
of muscular exercise on, 280
of superior laryngeal nerve on,
278,301
of vagi on, 276, 300
internal, 222, 265
mechanical phenomena of, 225
methods in chemistry of, 239, 305,
306
of muscle, 269
Respiration, regulation of, 276, 281
types of, 229
Respiratory apparatus, physiological
anatomy of, 223
capacity, 236, 303
centre, 274
action of carbon dioxide on, 281,
282
of deficiency of oxygen
on, 281
automaticity of, 284
spinal, 285
' dead space,' 236
exchange, 239, 242, 243, 305
gravimetric method, 240, 306
Zuntz's method, 239
movements, tracings of, 233, 278,
279, 280, 289, 301, 362
in man, 233, 289, 301
recording of, 233, 301
pressure, 238, 304
quotient, 241
sounds, 231
tracings, 233, 278, 279, 280, 289, 301,
302
Restifonu body, 885, 892
Resuscitation of heart, 153
of central nervous system, 990
scratch reflex in, 908
Reticular formation, 865, 870
Retina, development of, 850
epithelium, pigmented, 1048
fatigue of, 1049, 1055, 1056, mi
formation of image on, 1017, 1102
intermittent stimulation of, 1050,
sensibility of different parts, 1058
time needed for excitation, 1049
Retinoscope, Geneva, 1 1 10
Retinoscopy, 1034, 1109
Reverser, current, 732
Rheocord, 727, 810
Rhinencephalon, 922, 968
Rhodopsin, 1046
Ribose, 593
Right-handed people, aphasia in, 971
Rigor, heat-, production of carbon
dioxide in, 270, 777
mortis, 774
and muscular contraction, 776
production of carbon dioxide
in, 270, 777
of lactic acid in, 776,
208
removability of, 779
time of onset of, 776, 778
production of heat in, 778
Ringer's solution, 66
Ritter's tetanus, 831, 846
Ritter-Valli law, 785
Riva-Rocci apparatus for blood-pressure,
"3,213
1240
IXDEX
Rolandic area of cortex, 951
sensory function of, 963
fissure, 875
Thane's rule, for position of,
956, 963
Rontgen rays for study of gastro-intes-
tinal movements, 327, 328
Rouleaux formation, 16
Rubro-spinal tract, 867
connections of, 884
Saliva, action of, in stomach, 348, 417
amylolytic action of, 346, 454
antilytic secretion of, 398
chemistry of, 344, 454
effect of drugs on secretion of, 392,
394,457
freezing-point of, 387
functions of, 346
paralytic secretion of, 397
psychical secretion of, 399
reflex secretion of, 398
Salivary centre, 400
glands, cranial nerves of, 391, 394,
396,456
extirpation of, 673
oxygen consumption in, 266,
268
secretory changes in, 375, 382
secretory pressure in, 393
sympathetic nerves of, 391, 394,
397, 457
trophic-secretory fibres of, 395
Salt hunger, 381, 621
solution, physiological, 194
Salts, absorption of, 446
in diet, 620, 625, 629
in food, r61e of, in nutrition, 625
Saponification, II, 367, 421
Saponin, laking of blood by, 70
Sarkin, 589
Scalene muscles in respiration, 227
Schemer's experiment (vision), 1031, 1103
Schiitz's law of ferment action, 342
Sclero-proteins, 2
Scratch reflex, 901
in resuscitation, 908
Scurvy and deficiency in diet, 632
Sealing of wounded vessels, 46
Sebaceous glands, fat formation in, 565
Sebum, 512
Secondary contraction, 203, 833, 842
Secretin, 407
Secretion, internal, 635
Segmentation of food in intestine, 329
Semicircular canals and equilibration,
936
Semilunar valves, 89
and dicrotic wave, 105
moment of closure of, 96
Semisection of cord, effects of, 894
Sensation, relation of stimulus to, iioo
Sensations, cold, 1082
cutaneous, 1078
heat, 1 08 1
hunger, 1096
muscular, 1094
ordinary, cerebral localization of, 968
pain, 1083
tactile, cerebral localization of, 968,
969
thirst, 1096
touch, 1078, 1080
Sensibility, recurrent, 797, 892
Sensori-motor area, 963
Sensory aphasia, 972
areas, visual centres, 923, 965
functions of Rolandic area, 963
paths, decussation of, 894
in internal capsule, 881
scheme of, 880
Septo-marginal bundle, 868
Serin, 360
Serratus posticus, action of, in respira-
tion, 227
Serum, action of, on artery rings, 46, 66
albumin, 47, 65, 575, 819
coagulation of, 47
composition of, 47, 65
globulin, 34, 47, 65, 575
immune, 31
inorganic salts of, 49
proteins, 49, 65, 572
Sexual organs, internal secretion of, 640
Sham feeding, 402
Shock, anaphylactic or protein 32
spinal, 888, 912
surgical or vascular, 192
Sighing, 288
Sino-auricular node, 81
Sinus venosus, 80, 81, 141, 194
stimulation of, 198
Skate, electrical organ, 841
Skatol, 424
formation of, in intestine, 422
Skatoxyl in urine, 484, 518
Skiascopy, 1034, 1109
Skin, action currents of, 838
effects of varnishing, 299, 699
excretion by, 511
respiration by, 299
sensations, 1078
Smell, 1075, 1114
centre for, 922, 967
Smooth muscle, composition of, 768
Snake-venom, effect of, on coagulation
43
Sneezing, 288
Solutions, scheme for testing, 13
Sorbite, 3
Specific energy of nerves, o/O
dynamic action of foods, 686
Speech, 312
nervous mechanism of, 315
INDEX
1241
Spermin, 642
Sphincter ani, 320, 333
cardiac, 320, 324, 331, 335, 336
ileo-colic, 331, 335, 421
pylori, 320, 326, 327, 331, 335,
418
vesicae, 510
Sphygmograph, Marey's, 103
Dudgeon's, 208
Sphygmographic tracings, 103, 104, 209
Sphygmomanometer of Erlanger, 114
of Hill and Barnard, 115
Spinal accessory nerve, 931
united with facial, 976
cord and bulb, centres of, 919
automatism of, 916
conduction of nervous im-
pulses by, 890
consciousness in, 889
effects of transection of, 888
grey matter of, 863
reflex action of, 897
scheme of cross-section of, 867
section of, to show tracts, 865
semisection of, effects of, 894
ganglia and reflexes, 912
cells of, 854
development of, 850
fatigue of, 913
roots, degeneration of, 797
function of, 891
shock, 888, 912
Spinotectal fibres, 874
Spino-thalamic fibres, 874
Spirograph of Fitz, 233, 300
Spirometer, 235, 303
Splanchnic nerves and adrenals, 661
and hyperglycaemia, 547, 550
and intestines, 332
and kidneys, 506
vasomotors in, 177
Spleen and hcematopoiesis, 21
and pancreas, mutual relations of,
411
functions of, 672
grafting of, 672
proteolytic enzyme of, 411
Spongioblasts, 849
Staircase phenomenon, 156, 749
Standing, 945
Stannius' experiment, 144, 194, 199
Starch, tests for, II
Starvation, excretion of urea in, 604
loss of weight of organs in, 603
metabolism in, 604
protein metabolism in, 602
Stasis, 61, 103
Steapsin, 358, 363, 461
Stearic acid, 556, 558
Stercobilin, 424
Stereognosis, 963
Stereoscopic vision, 1039
Sterins, or sterols, 366
digestion of, 421
metabolism of, 570
Stilling, cervical and sacral nuclei of, 864
Stimulants in diet, 630
Stimulation by voltaic current, 741, 784,
810, 845
chemical, 73^783
law of polar, 741, 810, 845
recording beginning and end of, 201
Stimuli, adequate, 901, 979, 1007
different kinds of, 737
summation of, 756, 816
Stimulus, relation of, to sensation, noo
Weber's law, noo
Stokes- Adams disease, 150
Stomach, absorption of proteins by, 418
auto-digestion of, 388, 465
digestion of fat in, 355, 421
excision of, 357
movements of, 326
nerves of, 331, 401
pouch, 403
protection from gastric juice, 388
Striae acustica?, 928
Striped muscle, structure of, 742
Stromuhr, 120
Strychnine and reversal of reflexes, 904
effect of, on reflexes, 899
in localization of sensory cortical
zones, 968
Substantia nigra, 870
Substrate, 338
Succus entericus, 370. See Intestinal
juice
Suckling, food requirement of, 628
Sugar and muscular work, 541, 772
constitution of, 537
consumption of, in diabetes, 554
destruction of, 541
formation of, from amino- acids, 538,
545, 590
from fatty acids, 538, 545, 566
in blood, 47, 50, 446, 499, 500, 540,
552, 717
intermediary metabolism of, 542
in urine, tests for, 488, 525
regulating centre, 548
mechanism, 547
tolerance, 540, 551, 637
Sulphates in urine, 484
estimation of, 517
Sulphocyanide in saliva, 346, 454
Summation of stimuli, 756, 816
Superposition of contractions, 756, 816
Supplemental air, 236, 303
Suprarenal capsules and coagulation, 45
extract, effect of, on blood-pressure,
173, 177, 216, 655
Suprarenals, 655. See Adrenals
Suprarenin. See Adrenalin and Kpi-
nephrin
1242
INDEX
Surface and mass of body, relation be-
tween, 695
heat-production and blood-flow, re-
lations of, 696
phenomena and absorption, 431
tension, 429
and musculaj^pontraction, 744
Surgical shock, 192 ^P
Suturing bloodvessels, 1145
Sweat-centre, 513
composition of, 511
function of, 514
quantity of, 512
secretion of, influence of nerves on,
513
Swim-bladder, secretion of gases in, 265
Sympathetic cardiac fibres of, in frog,
157, 196, 199
cervical, vaso-motor fibres in, 175
ganglion cells, action of nicotine on,
182
nervous system, 1003
vibration, 314, 760, 1073, 1113
Synapse, 852
resistance of, 899
Syntheses in the body, 542, 570, 571, 573,
578, 579, 58o, 591, 597
Systoles, extra, 155
Tachycardia, 930
Tactile sensations, 1079
cortical centres for, 968
paths for, 896
Tadpole test for thyroid active substance,
653
Talbot's law, 1040, 1113
Tambour, 91
for respiratory movements, 233
Marey's, 208
Taste, 1077, 1113
centre for, 968
nerves of, 925
Taurin, 365, 579
Taurocholic acid, 365, 462
Tea, 594, 630
Tears, 475
Teeth, 320
Tegmentum, 870, 874
Telencephalon, 850
Telodendrion, 852
Temperature, 674
daily curve of, 712
discrimination, 1116
in cavities of heart, 710
in mouth, 712
in rectum, 712
normal variations in, 713
of blood, 711
of body, 680
measurement of, 675
of brain, 689, 712
of coagulation, 9
Temperature of different parts, 711, 712
of skin, 6/6, 712
post-mortem rise of, 714
regulation, 690
influence of curara on, 693
in hibernating animals, 703
sensations, 1082, 1088, 1092, 1115
paths for, 896
topography, 709
Tension of carbon dioxide in blood, 261,
264
of gases, 247
in alveoli, 241, 263
of oxygen in blood, 253, 261
measurement of, 258
surface. See Surface tension
Testes, interstitial cells of, 641
Testicle, action of extracts of, 642
Testicles, internal secretion of, 640
Tetanizing current, arrangement for,
2OO
Tetanus (electrical), composition of, 756,
816
Hitter's, 831,846
secondary, 203, 833, 842
toxin effect of, on reflexes, 899
Tetany, after parathyroidectomy, 646
Tethelin, 670
Thalamico-spinal tract, 867, 885
Thane's method for position of fissure of
Rolando, 956, 963
. Theine, 481, 583, 594, 632
Theobromine, 481, 583, 594, 631
Theophyllin, 481, 594
Theory, Hering's, of colour vision, 1057
of identical points, 1037
Young-Helmholtz, 1053
Thermo-electric junction, 675, 680, 763
Thermogenic nerves, 780
Thermometer, electrical resistance, 676,
677, 783
maximum, 675
Thermometry, 674
Thermopile, 763
Thermotaxis, 690
Thirst, sensation of, 930, 1099
Thiry's fistula, 370
Thrombin, 35
formation of, 36
'nature of action on fibrinogen, 41
preparation of, 41
specificity of, 40
Thrombocytes. See Blood plates
Thrombogen, 36
sources of, 38
specificity of, 40
Thrombokinase, 36
preparation of, 65
sources of, 38, 40
specificity of, 40
Thromboplastic substances, 41
Thrombo-regulative mechanism, 43
INDEX
Thrombosis, 45
Thrombotaxis, 42
Thumb centre, 973
Thymin, 593
Thymus, involution of, 644
grafting of, 645
lymphocytes of, 643
relation of, to sexual glands, 644
removal of, 645
Thyroid and heat-production, 650, 699
changes with meat diet, 650
grafting of, 648
hyperplasia of, 649
influence of iodine on, 650
of nutritive conditions on, 649
iodine in, 652
influence on tadpoles, 653
nerves of, 653
Thyroidin, 649
Thyroids, effects of excision of, 647,
648
Tickling, sensation of, 1078, 1080
Tidal air, 235
measurement of, 303
Timbre of sounds, 310
of vowels, 313
Time-markers, 195, 732
Tissue extracts and coagulation, 36
respiration, 265, 269
Tissues, cultivation of, outside the body,
1142
gas tensions in, 267
transplantation of, 641, 1142
Tone of muscles, 917
vase-motor, 184
Tonsils, 320
Topognosis, 963
Torpedo, 840
Torricelli's theorem, 83
Touch, 1079, 1080, 1114
spots, 1080
Trachea, to put a cannula in, 202
Tracheal cannula, 201
Tracts in spinal cord, 865
myelination of, 961
Transfusion, influence on blood- pressure,
191, 214
Transplantation of tissues, 641, 1142
Traube-Hering curves, 294
Tricuspid valve, 86, 96
Trigeminus nerve, 924
Tripalmitin, 556
Tristearin, i, 556
Trochlear nerve, 924
Trommer's test, for sugar, 10, 525
Trophic nerves, 805
tone, 919
Trypsin, 345, 358, 359, 411, 418, 420,
460
Trypsinogen, 358, 372, 377, 389, 39*
Tryptophane, 2, 360, 487, 615
' Twitch,' 745, 8 II
Tympanum, 1065
Tyrosin, 2, 360, 462, 488, 575, 576
Morner's test for, 462
Tyrosinase, 272
Uffelmann's test for lactic acid, 460
Ultra-microscope, coagulation studied
by, 39
Uncinate gyms, 968
Uracil, 593
Urea, in blood, 47, 499
estimation of, 518, 520
excretion of, by kidney, 492, 496, 497,
498, 502
in fever, 706, 707
in starvation, 604
premortal rise in starvation,
603
formation of, 583
processes of formation of, 588
Urease, 478
method of estimating urea, 518
Uric acid, 481,523
destruction of, 595
exogenous and endogenous, 595
formation of, 585, 590
in gout, 487, 590
sources of, 591
Uricolysis, 595, 596
Uricoxydase, 596
Urine, acidity of, 478, 479, 515
albumose in, 509, 525, 572
alkaptori in, 483, 581
amino- acids in, 481, 488, 579
ammonia in, 480, 519, 521
bile-pigments in, 483, 531
bile-salts in, 489, 528, 531
carbo-hydrates in, 482
chlorides in, 477, 483, 515
composition of, 476
creatinin in, 481, 523
cystin in, 488, 532, 579
ethereal sulphates in, 484, 517
expulsion of 510
ferments in, 483
freezing-point of, 485, 529
, haematoporphyrin in, 483
hippuric acid in, 481, 524
in disease, 485, 524
in fever, 703
incontinence of, 511
indican, indoxyl in, 484, 487, 517
oxalic acid in, 478, 481, 532
phenol in, 484, 604
phosphates in, 483, 516
physico-chemical analysis of, 485,
529
pigments of, 482
proteins in, 482, 488, 524
purin bases in, 481
reabsorption of, from the tubules,
494, 502
1244
INDEX
Urine, secretion of, 489
Heidenhain's experiments on,
495
influence of circulation on, 506
of nerves on, 508
Nussbaum's experiments on,
498
pigments, by the kidney, 495
theories of, 491, 502
work done by kidney in, 504
secretory pressure of, 506
sediments of, 478, 479, 488, 531
skatoxyl in, 484, 518
specific gravity of, 476, 515
sugar in, 487, 488, 526
sulphates in, 484, 517
systematic examination of, 531
temperature of, 712
total nitrogen in, 477, 521
urea in, 480, 487, 518
uric acid in, 480, 487, 523, 531
Urobilin, 365, 424, 482
Urobilinogen, 365
Urochrome, 482
Uroerythrin, 482
' Urohypertensine,' 672
Urorosein, 482
Uterus rings and segments, isolated, 1147
Utricle, 936, 1067
Vago-sympathetic nerve, in frog, 141,
196, 198, 199
Vagotomy, death after double, 286
Vagus, stimulation during resuscitation
after cerebral anaemia, 187
in mammals, 162, 164, 203, 212
inspiratory and expiratory fibres in,
276-279
negative variation of, 277, 828
nerve, functions of, 929
of frog, dissection of, 196
relation of, to respiration, 276
stimulation of, in dog, 203, 212
in frog, 198
Valin, 360
Valsalva's experiment, 296
Valves of veins, 82
semilunar, moment of closure, 96
Varnishing the skin, 299, 514, 699
Vaso-constrictor and vaso-dilator nerves,
173
differences in excitability of, 175
property of shed blood, 45
Vaso-dilator fibres, 179
in cervical sympathetic, 176
Vaso-dilators of chorda tympani, 179,
392
of nervi erigentes, 179, 180
Vaso-motor centres, 182
anatomical relations of, 185
nature of tone of, 184
spinal, 183
Vaso-motor nerves, 173, 175, 176
course of, 181
in cervical sympathetic, 175
in splanchnic, 177
in trigeminus, 176
of brain, 176
of extremities, 177
of heart, 178
of lungs, 179'
of muscle, 178
of veins, 180
reciprocal relations of, 186
reflexes, 185, 212
studied by calorimetric method.
188, 221
tone, 184
Vaso-motors, methods of investigating,
174
Veins, action of adrenalin on, 181,
circulation in, 132
factors concerned in flow in, 133
pressure in, 132
measurement of, in man, 133
pulse in, 100, 131
vaso- motor nerves of, 180
velocity of blood in, 134
Vella's fistula, 370
Velocity of blood, 117, 127
in capillaries, 130
in veins, 134
measurement of, 120
Vena portae, vaso-motor nerves of, 180
Venous blood, tension of carbon idoxide
in, 261
pressure-curve, 98, 100
pulse, 99, 100, 131, 134
tracing, 100, 209
Ventilation, 242
pulmonary, 235, 281
Ventricle, suction action of, 101
Ventricular pressure-curve, 94
Veratrine, action of, on muscle, 754, 814
Vesicular murmur, 231
Vestibule, paths from, 928
Vestibulo-spinal tract, 867
connections of, 884
Visceral pain, 891, 901
Visuo-psychic area of Campbell, 966
Vision, after-images, 1055
apparent size of objects, 1042
astigmatism, 1031, 1105
blind spot, 1044, 1107
colour, 1051
Hering's theory, 1057
mixing, 1053, mi
triangle, 1054
Young-Helmholtz theory, 1053
colour-blindness, 1059, 1112
comparative anatomy, 1013
contrast, 1056
duration of stimuli, 1049
Fick's persistence theory, 1050
INDEX
1245
Vision, Holmgren's wools, 1112
irradiation, 1061
Listing's law, 1063
Maxwell's spot, 1107
measurement of field of, 1058, 1106
ophthalmometer, 1021, 1105
ophthalmoscope, 1031, 1108
perimetry, 1058, 1106
Purkinje's figures, 1042, 1113
relation of rods and cones to, 1045
skiascopy, 1034, 1109
stereoscopic, 1039
Talbot's law, 1050, 1113
theory of identical points, 1037
Visual acuity, mi
centres, 965
path, 883, 923, 966
purple, 840, 1047
Vital capacity, 236, 303
Vitamines, 617, 632
Vitreous humour, 466, 1016
Vivi-diffusion apparatus, 48
Vocal cords, 307
in voice production, 308
movements of, in respiration,
3"
paralysis of, 316
Voice, 307
air-pressure necessary for, 309
falsetto, 312
in children, 310
nervous mechanism of, 315
Voltaic current, alterations in excita-
bility and conductivity by,
785-788, 844-846
stimulation by, 741, 784, 810
Volume pulse, 127
Voluntary contraction, 760
electrical changes in, 762
fatigue in, 753
movements, acquisition of, 981
Vomiting, 335
centre, 336
Vomiting, induced by apomorphine, 336,
459, 464
Vowel cavities, 314
formation, theories of, 314
Vowels, timbre of, 313
Warmth, sensations of, 1081
Water, absorption of, 446
in diet, 629
production of, in the body, 620
Weber's law (stimuli), noo
Wernicke, aphasia of, 971
zone of, 971
Wharton's duct, 391
insertion of cannula in, 456
Wheatstone's bridge, 726
Whey protein, 354, 719
Word-blindness, 972
-deafness, 967, 972
Wounded vessels, sealing of, 46
Xanthin, 481, 589, 592, 593
fever, 707
Xantho-proteic reaction, 8
Xerostomia, 400
Yawning, 288
Yeast and vitamines, 633
test for sugar, 488, 526
Yellow atrophy, acute, and excretion of
amino-acids, 586
spot, 975, 1107
Yohimbine, action on refractory period
in nerve, 783
vaso-dilator action on submaxillary,
392
Youug-Helmholtz theory of colour vision,
1053
Zein, as a food, 615
Zoosterins, 366, 570
Zymase, 337
Zymogen, 351, 356, 382, 383, 389
granules, 376
BAILLIERE, TINDALL AND COX, 8 HENRIETTA STREET, COVKNT GARDEN, LONDON
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