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1 Spectrum oP Ardand-lamp with PraunhoPErs lines in position. 

2 Spectrum oP Dxyhsmodlobin in diluted blood. 
.'3 Spectrum aP Reduced nsmoQlobin. 

4 Spectrum aP Carbonic oxide Hsmp^iobio. 
o Spectrum oP AcidHsmatm in ethErial solution. 

6 Spectrum oP Alkaline HaEmatin. 

7 Spectrum Dp Chloroform extract oT acidulated Qx-Bile. 

8 Spectrum nP MethffimaQlabin. 

9 Spectrum oP HasmachromDi^Gn. 
10 Spectrum op Hsmetopnrphyrin. 

Mosfofth? above SjM>ctnr have keen (frown fmrn observations by MTWblpraik F.C.S. 




Revised and Rewritten by 



ftentb American IRcvtston 



: 2Z 






In this the tenth American edition of the Handbook of Physiology 
revisions and amplifications have been made throughout the entire text. 
New subject matter, new illustrations, and the more recent refinements of 
methods have been freely incorporated. This has unavoidably increased 
the size of the volume. The chapters on Circulation, Respiration, Internal 
Secretion, Metabolism and the Autonomic division of the Nervous System 
in particular have been entirely rewritten and reillustrated. 

The chapter on the Circulation has been made to include the newer 
researches on the development of cardiac physiology as regards rhythm 
production, the control and finer adjustments of rate, and the conduction 
phenomena that determine sequence. These factors, represented in the 
highly differentiated bundle branch system, are given new emphasis and 
new illustration. Physiological interest in Respiration has been inten- 
sified by the practical problems of air navigation and by the newer inves- 
tigations in the field of oxygen supply and oxygen control in relation to the 
daily physiological round in both health and disease. The result has 
been a new impetus to respiratory physiology contributed to by numerous 
writers of the last decade. The works of Barcroft, Henderson, Schneider, 
Greene and Gilbert and numerous others have been drawn on from this 

The science of nutrition has made rapid advances. That subject has 
been revised to call attention to the very fundamental work of Osborne 
and Mendel on food factors necessary for growth; of Funk, Voegtlin and 
others on the vitamines and nutritional diseases; of Lusk and DuBois in 
the field of basal metabolism; of Van Slyke, Stadie, Harrop, and others 
on blood gases, and of Banting, Best and Macleod on glycemia and the 
hormone of the pancreas controlling sugar metabolism. 

The giant strides of the science of physiology make it difficult for a 
textbook to keep pace with the literature, but it is hoped that the newest 
facts and principles have been incorporated in so far as the limitations 
of the available space permit. Many of the illustrative laboratory experi- 
ments have been again rewritten," and improvements simplifying the 
experimental technique have been incorporated. It is felt that the student 
in Physiology gains the greatest strength in laboratory experience when 
the tests he executes are chosen from the standpoint of the efficiency of the 
entire work. In this field, under the present day conditions, the deter- 


mining pedagogical horizon includes not only the subject matter of 
Physiology, but of Physics and Chemistry on which Physiology rests, as 
well as Clinical Medicine and Surgery for which Physiology furnishes the 

For valuable aids and criticisms in this and recent editions I again 
acknowledge grateful indebtedness to Professor Robert Banks Gibson, 
University of Iowa, Dr. Carl Hartley Greene, Mayo Foundation, to my 
colleague, Professor Addison Gulick, and to my students and assistants 
of former years, Professor Theodore K. Kruse of the University of 
Pittsburgh, and Professor Erwin Ellis Nelson of the University of 

Sept. i, 1922. 



CHAPTER I THE PHENOMENA or LIFE; Properties of Protoplasm, 

Structure of Protoplasm i 

ELEMENTARY TISSUES; The Structure of the Cell, The Structure 
of the Elementary Tissues. The Epithelial Tissues. The 
Connective Tissues. Muscular Tissue. Nervous Tissue. 17 

Nitrogenous Substances, The Proteins, Classification of the Pro- 
teins, Characteristics of the Proteins, The Fats, The Carbo- 
hydrates; Inorganic Substances of the Body, Laboratory Experi- 
ments 79 

CHAPTER IV THE BLOOD; Quantity of the Blood, Coagulation of 
the Blood, Morphology of the Blood, Chemical Composition of 
the Blood, Globulocidal and Other Properties of Serum, The 
Character and Composition of Lymph, Laboratory Experiments 117 

siderations, The Action of the Heart, The Regulative Influence of 
the Central Nervous System, The Circulation through the Blood- 
vessels, The Pulse, The Peripheral Regulation of the Flow of 
Blood, Vaso-constrictor and Vaso-dilator Nerves for Individual 
Organs, Laboratory Experiments 166 

CHAPTER VI RESPIRATION; The Respiratory Apparatus, The 
Movements of the Respiratory Mechanism, Respiratory Changes 
in the Air Breathed, The Respiratory Changes in the Blood, The 
Nervous Regulation of the Respiratory Apparatus, The Effect of 
Respiration on the Circulation, Laboratory Experiments in 
Respiration 278 

Secretion, Secreting Glands, The Process of Secretion, Influence 
of the Nervous System on Secretion 335 




The Process of Digestion, Digestion in the Mouth, Deglutition, 
Nervous Mechanism of Deglutition, Digestion in the Stomach, 
Movements of the Stomach, Digestion in the Intestines, Move- 
ments of the Intestines, Laboratory Experiments in Digestion, 
Saliva and Salivary Digestion, Gastric Juice and Gastric Diges- 
tion, Pancreatic Juice and Pancreatic Digestion 341 

CHAPTER IX ABSORPTION; Absorption in the Stomach, Absorp- 
tion in the Intestines, Absorption from the Skin , the Lungs, etc. . 41 1 

CHAPTER X EXCRETION; Structure and Function of the Kidneys, 
General Structure, The Urine, The Method of Excretion of Urine, 
The Discharge of the Urine, The Structure and Excretory Func- 
tions of the Skin, Laboratory Experiments in Excretion . . . .421 

Proteids, The Metabolism of Fats, the Metabolism of Carbohy- 
drates, Influence of Minerals, Fasting, Requisites of a Normal 
Diet, The Vitamines, The Influence of the Ductless Glands on 
Metabolism 454 

CHAPTER XII ANIMAL HEAT; Heat-producing Organs, Variation 
in the Loss of Heat, Variation in the Production of Heat, Influ- 
ence of the Nervous System on Heat Production 501 

tion of Muscle, The Properties of Living Muscle, Single Muscle 
Contractions, Conditions which Affect the Irritability of the 
Muscle and the Character of the Contraction, Tetanic and Volun- 
tary Muscular Contractions, The Type of Contraction in Invol- 
untary Muscle and in Cilia, The Function of Nerve Fiber, Some 
Special Coordinated Motor Activities, Locomotion, The Produc- 
tion of the Voice, Laboratory Experiments on Muscle and Nerves. 5 10 

CHAPTER XIV THE NERVOUS SYSTEM; Function of the Nerve Cell; 
Specific Energy of the Nerve Impulse, Structure and the Function 
of the Spinal Cord, Tracts of the Cord, The Functions of the Cord. 
The Brain, The Medulla Oblongata and Pons, Structure, Func- 
tions of the Medulla, The Cerebellum, The Midbrain, The 
Peduncles of the Cerebrum, Corpora Quadrigeminaj Corpora 
Genic.ulata, Corpora Striata, The Cerebrum, Structure of the 
Cortex, General Function of the Cerebrum, Localization of the 



Motor Function, Localization of Sensory Function, Association 
Centers, The Cranial Nerves, The Sympathetic or Autonomic 
System, The Physiology of Sleep, Laboratory Experiments on 
the Nervous System 572 

CHAPTER XV THE SENSES; I. The Senses of Touch, Pain, Tem- 
perature, and the Muscle Sense. II. Taste and Smell, The Sense 
of Taste, The Sense of Smell. III. Hearing and Equilibration, 
The Anatomy of the Ear, The Physiology of Hearing, The Sense 
of Equilibrium. IV. The Sense of Sight, The Eye, The Optical 
Apparatus, Accommodation, Defects in the Optical Apparatus, 
Visual Sensations from Excitation of the Retina, Color Sensations, 
Binocular Vision, Visual Judgments, Laboratory Directions for 
Experiments on the Sense Organs 679 

Organs of the Male, The Reproductive Organs of the Female, 
Ovulation and Menstruation, Menstrual Life 768 

CHAPTER XVII DEVELOPMENT; Changes which Occur in the 
Ovum Prior to Impregnation, Changes Following Impregnation, 
Circulation of Blood in the Fetus, Parturition, Lactation . . . 781 

INDEX 797 



PHYSIOLOGY is the science which treats of the various processes or changes 
which take place in the organs and tissues of the body during life. These 
processes, however, must not be considered as by any means peculiar to the 
human organism, since, putting aside the properties which serve to distin- 
guish man from other animals, the changes which go on in the tissues of man 
go on in much the same way in the tissues of all other animals as long as they 
live. Furthermore, it is found that similar changes proceed in all living 
vegetable tissues; they indeed constitute what are called vital phenomena, 
and are those properties which mark out living from non-living material. 

The lowest types of life, whether animal or vegetable, are found to con- 
sist of minute masses of a substance generally known under the name of 
protoplasm. Each such living mass is called a cell, so that these minute 
elementary organisms are designated unicellular. 

The phenomena of life are exhibited by protoplasm, whether that exists 
in the simple form typified by a microscopic one-celled animal, or in a more 
complex mass represented by the organs and tissues of animals and plants. 
In the lowest type of life the morphological unit of structural organization is 
represented by the single cell. In the more complex organisms of both ani- 
mals and plants the total mass represents a great aggregation of more or less 
distinct cells. A degree of differentiation takes place whereby the tissues 
and organs of the body of plants and animals present great aggregates of 
differentiating cells. It must be at once evident that the great mass of knowl- 
edge dealing with the nature and activities of protoplasm constitutes the 
science of physiology. The cell, therefore, is the working unit in physiology 
no less than in morphology. 

The prime importance of the cell as an element of structure was first 
established by the researches of the botanist Schleiden, and his conclusions, 
drawn from the study of vegetable histology, were at once extended by Theo- 
dor Schwann to the animal kingdom. The earlier observers defined a cell 
as a more or less spherical body limited by a membrane, and containing a 
smaller body termed a nucleus, which in its turn incloses one or more still 



Space contain- 
ing liquid. 



Cell wall. 

FIG. i. Vegetable Cells. 

smaller bodies or nucleoli. Such a definition applied admirably to most vege- 
table cells, but the more extended investigation of animal tissues soon 
showed that in many cases no limiting membrane or cell wall could be 

The presence or absence of a cell wall, 
therefore, was then regarded as quite a 
secondary matter, while at the same time the 
cell substance came gradually to be recog- 
nized as of primary importance. Many of 
the lower forms of animal life, the Rhizopoda, 
were found to consist almost entirely of 
matter very similar in appearance and chem- 
ical composition to the cell substance of 
higher forms; and this from its chemical 
resemblance to flesh was termed Sarcode 
by Dujardin. When recognized in vege- 
table cells it was called Protoplasm by 
Mulder, while Remak applied the same name 
to the substance of animal cells. As the 
presumed formative matter in animal tissues 

it was termed Blastema, and in the belief that, wherever found, it alone of 
all substances has to do with generation and nutrition, Beale has named 
it Germinal matter or Bioplasm. Of these terms the one most in use 
at the present day as we have already said, is protoplasm, and inasmuch as 
all life, both in the animal and vegetable kingdoms, is associated with 
protoplasm, we are justified 
in describing it, with Huxley, 

i <k i -11 P IT )> /^i^S^SwSSBSSS^ilK Nucleus or ger- 

as the "physical basis of life," .K^BV-- minai vesicle. 


or simply "living matter." 

General Physical a n d 
Chemical Properties of Pro- 
toplasm. Protoplasm is a 
semifluid substance, which ab- 
sorbs, but does not mix with 
water. It is transparent and 

generally colorless, with refrac- FlG - 2. Semidiagrammatic Representation of 

, a Human Ovum, showing the parts of an animal 
tive index higher than that of ce \\ m (Cadia.) 

water, but lower than that of oil. 

It is neutral or weakly alkaline in reaction, but may under special cir- 
cumstances be acid, as, for example, after activity. It undergoes heat 
coagulation at a temperature of about 54.5 C. (130 F.), and hence no 
organism can live when its own temperature is raised above that point. 
It is also coagulated and therefore killed by alcohol, by solutions of 

minal spot. 
----Space left by re- 
traction of yolk. 

Vitellus of yolk. 

Vitelline mem- 


many of the metallic salts, by strong acids and alkalies, and by many 
other chemical substances. 

Under the microscope it is seen almost universally to be granular, the 
granules consisting of different substances, albuminous, fatty, or carbo- 
hydrate matter. The granules are not equally distributed throughout the 
whole cell mass, as they are sometimes absent from the outer part or layer 
and very numerous in the interior. In addition to granules, protoplasm 
generally exhibits spaces or vacuoles, usually globular in shape, except- 
ing during movement, when they may be irregular, and filled with a watery 
fluid. These vacuoles are more numerous and pronounced in vegetable 
than in animal cells. Gas bubbles also sometimes exist in cells. 

It is impossible to make any definite statement as to the exact chemical 
composition of living protoplasm, since the methods of chemical analysis 

FIG. 3. Phases of Ameboid Movement. 

necessarily imply the death of the cell; it is stated, however, that protoplasm 
contains 75 to 85 per cent, of water, and of the 15 to 25 per cent, of solids the 
most important part belongs to the class of substances called proteins or al- 
bumins. Proteins contain the chemical elements carbon, hydrogen, nitrogen, 
oxygen, sulphur, and phosphorus, the last two in very small quantities only. 
A protein-like substance, nudein, found in the nuclei of cells, contains phos- 
phorus in greater abundance. In the cell nucleus a compound of nuclein 
with protein, called nucleoprotein, forms the most abundant protein sub- 
stance. Other bodies are frequently found associated with the proteins, such 
as glycogen, starch, cellulose, which contain the elements carbon, hydrogen, 
and oxygen, the last two in the proportion to form water, and hence are 
termed carbohydrates; fatty bodies, containing carbon, hydrogen, and oxygen, 
but not in proportion to form water; lecithin, a complicated fatty body con- 
taining phosphorus; cholesterin, a monatomic alcohol; chlorophyll, the color- 
ing matter of plants; hemoglobin, the complex animal pigment; inorganic 
salts, particularly the chlorides and phosphates of calcium, sodium, and potas- 
sium ; ferments, and many special substances. 

The General Physiological Characteristics of Protoplasm. The 
properties of protoplasm may be well studied in the microscopic animal called 
the ameba, a unicellular organism found chiefly in fresh water. These 
properties may be conveniently studied under the following heads: 

The Power of Spontaneous Movement. When an ameba is observed 
with a high power of the microscope, it is found to consist of an irregular mass 


of protoplasm containing one or more nuclei, the protoplasm itself being 
more or less granular and vacuolated. If watched for a minute or two, an 
irregular projection is seen to be gradually thrust out from the main body; 
other masses are then protruded until gradually the whole protoplasmic sub- 



FIG. 4. Changes of Form of a White Corpuscle, Sketched at Brief Intervals. The figures 
show also the ingestion of two small granules. (Schafer.) 

stance is, as it were, drawn over to a new position, and when this is repeated 
several times we have locomotion in a definite direction, together with a con- 
tinual change of form. These movements, figures 3 and 4, are observed in 
such cells as the colorless blood corpuscles of higher animals, in the branched 
corneal cells of the frog and elsewhere, and are termed ameboid. 

FIG. 5. Cell of Tradescantia Drawn at Successive Intervals of Two Minutes. The 
cell contents consist of a central mass connected by many irregular processes to a peripheral 
film, the whole forming a vacuolated mass of protoplasm, which is continually changing 
its shape. (Schofield.) 

The remarkable movement of pigment granules observed in the branched 
pigment cells of the frog's skin by Lister are also probably due to ameboid 
movement. These granules are seen at one time distributed uniformly 
through the body and branched processes of the cell, while at another time 
they collect in the central mass leaving the branches quite colorless. 

This movement within the pigment cells might also be considered an ex- 
ample of the so-called streaming movement not infrequently seen in certain 
of the protozoa, in which the mass of protoplasm extends long and fine proc- 


esses, themselves very little movable, but upon the surface of which freely 
moving or streaming granules are seen. A gliding movement has also been 
noticed in certain animal cells; the motile part of the cell being composed of 
protoplasm bounding a central and more compact mass. By means of the 
free movement of this layer, the cell may be observed to move along. 

In vegetable cells the protoplasmic movement can be well seen in the 
hairs of the stinging-nettle and Tradescantia and in the cells of Vallisneria. 
It is marked by the movement of the granules nearly always embedded in it. 
For example, if part of a hair of Tradescantia, figures 5 and 6, be viewed 
under a high magnifying power, streams of protoplasm containing crowds 
of granules hurrying along, like the foot passengers in a busy street, are 
seen flowing steadily in definite directions, some coursing round the film 
which lines the interior of the cell wall, and others flowing toward or away 
from the irregular mass in the center of the cell cavity. Many of these streams 
of protoplasm run together into larger ones and are lost in the central mass, 
and thus ceaseless variations of form are produced. The movement of 
the protoplasmic granules to or from the periphery is sometimes called 
vegetable circulation, whereas the movement of the protoplasm round the 
interior of the cell is called rotation. 

The first account of the movement of protoplasm was given by Rosel in 
1755, as occurring in a small Proteus, probably a large fresh- water ameba. 
His description was followed twenty years later by Corti's demonstration of 
the rotation of the cell sap in characeae, and in the earlier part of the last 
century by Meyer in Vallisneria, 1827; Robert Brown, 1831, in "Staminal 
Hairs of Tradescantia." Then came Dujardin's description of the granular 
streaming in the pseudopodia of Rhizopods and movements in other cells of 
animal protoplasm (Planarian eggs, von Siebold, 1841; colorless blood 
corpuscles, Wharton Jones, 1846). 

The Power of Response to Stimuli, or Irritability. Although the move- 
ments of the ameba have been described above as spontaneous, yet they 
may be increased under the action of external agencies which excite them 
and are therefore called stimuli. If the movement has ceased for the time, 
as is the case if the temperature is lowered beyond a certain point, move- 
ment may be set up again by raising the temperature. Contact with foreign 
bodies, gentle pressure, certain salts, and electricity produce or increase the 
movement in the ameba. The protoplasm is, therefore, sensitive or irritable 
to stimuli, and shows its irritability by movement or contraction of its 

The effects of some of these stimuli may be thus further detailed: 

a. Changes of Temperature. Moderate heat acts as a stimulant; the 
movement stops below o C. (32 F.), and above 40 C. (104 F.); between 
these two points the movements increase in activity; the optimum tempera- 


ture is about 37 to 38 C. Exposure to a temperature even below o C. 
stops the movement of protoplasm, but does not prevent its reappearance if 
the temperature is raised; on the other hand, prolonged exposure to a tem- 
perature of a little over 40 C. kills the protoplasm and causes it to enter 
into a condition of coagulation or heat rigor. 

b. Mechanical Stimuli. When gently squeezed between a cover and 
object-glass under proper conditions, a colorless blood corpuscle contracts 
and ceases its ameboid movement. 

c. Nerve Influence. By stimulation of the nerves of the frog's cornea, 
contraction of certain of its branched cells has been produced. 

d. Chemical Stimuli. Water generally stops ameboid movement, and by 
imbibition causes great swelling and finally bursting of the cells. In some 
cases, however (myxomycetes), protoplasm can be almost entirely dried up, 
but remains capable of renewing its movements when again moistened. 
Dilute salt solution and many dilute acids and alkalies stimulate the move- 
ments temporarily. Strong acids or alkalies permanently stop the move- 
ments; ether, chloroform, veratrum, and quinine also stop it for a time. 

Movement is suspended in an atmosphere of hydrogen or carbonic acid 
and resumed on the admission of air or oxygen, but complete withdrawal of 
oxygen will after a time kill the protoplasm. 

e. Electrical. Weak currents stimulate protoplasmic movement, while 

strong currents cause the cells to assume a 
spherical form and to become motionless. 

The Power of Digestion, Respiration, and 
Nutrition. This consists in the power which 
is possessed by the ameba and similar animal 
cells of taking in food, modifying it, building 
up tissue by assimilating it, and rejecting what 
is not assimilated. These various processes 
are effected in some one-celled animals by the 
protoplasm simply flowing around and en- 
closing within itself minute organisms such as 
diatoms and the like. From these it extracts 
what it requires, and then rejects or excretes the 
remainder, which has never formed part of the 
body. This latter proceeding is done by the 
cell withdrawing itself from the material to be 
excreted. The assimilation constantly taking 
place in the body of the ameba is for the 
purpose of replacing waste of its tissue conse- 
quent upon manifestation of energy. The 
respiratory process of absorbing oxygen goes 
on at the same time. 

FIG. 6. Cells from the Stam- 
inal Hairs of Tradescantia. A, 
Fresh in water; J5, the same cell 
after slight electrical stimula- 
tion; a, b, region stimulation; 
c, d, clumps and knobs of con- 
tracted protoplasm. (Kuhne.) 


The processes which take place in cells, both animal and vegetable, are 
summed up under the term metabolism (from /xera/itoA.^, change). The 
changes which go on are of two kinds, viz., assimilation, or building up, and 
disassimilation, or breaking down; they may be also called, using the nomen- 
clature of Gaskell, anabolism or constructive metabolism, and catabolism or 
destructive metabolism. In the direction of anabolism two processes occur, 
viz., the building up of special though non-living substances from materials 
which it takes in, and secondly, the building up of its own living substance 
from those or other materials. As we shall see in a subsequent paragraph, 
the process of 'anabolism differs to some extent in vegetable and animal 
cells. The catabolism of the cell consists in the disintegrative chemical 
changes which occur in the cell substance itself or in substances in contact 
with it. 

The destructive metabolism of a cell is increased by its activity, but goes 
on also during quiescence. It is probably of the nature of oxidation, and re- 
sults in the evolution of carbon dioxide and water on the one hand, and in the 
formation of various more complex chemical substances on the other, some of 
which may be stored up in the cell for future use, and are called secretions, 
and others, like carbon dioxide, for example, and bodies containing nitrogen, 
are eliminated as excretions. 

The Power of Growth. In protoplasm it is seen that the two processes of 
waste and repair go on side by side, and so long as they are equal the size 
of the animal remains stationary. If, however, the building up exceed the 

FIG. 7. Diagram of an Ovum (a) Undergoing Segmentation. In (b) it has divided 
into two, in (c) into four; and in (d) the process has ended in the production of the so-called 
"mulberry mass." (Frey.) 

waste, then the animal grows; if the waste exceeds the repair, the animal 
wastes; and if decay goes on beyond a certain point, life becomes impossible 
and the animal dies. 

The power of increasing in size, although essential to our idea of life, is 
not, it must be recollected, confined to living beings. A crystal of common 
salt, for example, if placed under appropriate conditions for obtaining fresh 
material, will increase in size in a fashion as definitely characteristic and as 
easily to be foretold as that of a living creature; but the growth of a crystal 
takes place merely by additions to its outside; the new matter is laid on par- 
ticle by particle, and layer by layer, and, when once laid on, it remains un- 
changed. In a living structure, where growth occurs, it is by addition of 
new matter, not to the surface only, but throughout every part of the mass, 
and this matter becomes an intimate part of the living substance. 



The Power of Reproduction. The ameba, to return to our former illus- 
tration, when the growth of its protoplasm has reached a certain point, mani- 
fests the power of reproduction, by splitting up into (or in some other way 
producing) two or more parts, each of which is capable of independent 
existence. The new amebae manifest the same properties as the parent, 
perform the same functions, grow and reproduce in their turn. This cycle 
of life is being continually passed through. 

In more complicated structures than the ameba, the life of individual 
protoplasmic cells is probably very short in comparison with that of the organ- 
ism they compose; and their constant decay and death necessitate constant 
reproduction. The manner in which this takes place has long been the sub- 
ject of investigation. 

The exact manner of reproduction and growth of protoplasm is a matter 
of great complexity. Those who have already learned the embryological 
story have the foundations laid for the physiological uses made of this mate- 

Cell membrane. 

Cell reticulum. - ^ 

Membrane of nucleus. 

Achromatic substance of 

Chromatic substance of 


FIG. 8. Cell with its Reticulum Disposed Radially; from the intestinal epithelium of a 

worm. (Carnoy.) 

rial. Certain of the essential facts are set forth in Chapter II a little later, in 
so far as the reproduction of the cellular unit is concerned. The reproduction 
of the animal organism as a whole is a still more complicated story and is 
presented in the last chapter of this volume. 


The Morphological Unit. Protoplasm was formerly thought to be homo- 
geneous. It is found, however, that every mass of living protoplasm has one 
or more special structures imbedded in the mass, the nuclei. In most tissues 
of the mammalian body each mass of protoplasm is more or less distinctly 
subdivided into elemental divisions, corresponding to the number of nuclei, 
the cells. The cells present in the mass, therefore, represent the morphologi- 
cal units. The arrangements of these units as to size and space relations 
constitute the form and mass characteristics of the tissues on the one hand, 
and of the organs on the other. Where there is no distinct marking off of 


the mass of protoplasm into individual cellular units, there is formed what 
is known as a syncytium. All syncytial structures are multi-nuclear, other- 
wise their protoplasm is not unlike that of the cell as a unit. 

The fuller detail of cellular types and cell structure is given a little later 
in Chapter II. However, for the purpose of reference to this point, one may 
here call attention to the fact that the principal differentiations of the proto- 
plasm of the cell are the nuclei and the cytoplasm. The cytoplasm is differ- 
entiated further into two substances, spongioplasm and hyaloplasm. The 
spongioplasm or reticulum forms a fine network, increases in relative amount 
as the cell grows older, and has an affinity for staining reagents. The 
hyaloplasm is less refractile, elastic, or extensile, and has little or no affinity 
for stains; it predominates in young cells, is thought to be fluid, and fills the 
interspaces of the reticulum. The nodal points of the reticulum, with the 
granular microsomes, found in the protoplasm, cause the granular appear- 
ance. The arrangement of the reticulum varies considerably in different 
cells, and even in different parts of the same cell. 

In some cells, particularly in plants, but also in some animal cells, there 
is a tendency toward the formation of a firmer external envelope, constituting 
in vegetable cells a membrane distinct from the more central and more fluid 
part of the protoplasm. In such cases the reticulum at the periphery of 
the cell is made up of very fine meshes. The membrane when formed is 
usually pierced with pores by which fluid may pass in, or through which 
protrusion of the protoplasmic filaments forming the cell's connection with 
other cells surrounding it may take place. 

FIG. 9. A: The Colorless Blood Corpuscle, Showing the Intracellular Network, and 
two nuclei with intranuclear network. B: Colored blood corpuscle of newt showing the 
intracellular network of fibrils. Also oval nucleus composed of limiting membrane and 
fine intranuclear network of fibrils. X 800. (Klein and Noble Smith.) 

All protoplasm at some period of its existence possesses one or more neclei. 
The origin of a nucleus in a cell is the first sign of the differentiation of proto- 
plasm. The existence of nuclei was first pointed out in the year 1833 by 
Robert Brown, who observed them in vegetable cells. They are either small 
transparent vesicular bodies containing one or more smaller particles called 
nucleoli, and always when in the resting condition bounded by a well-defined 


envelope. In their relation to the life of the cell they are certainly hardly 
second in importance to the cytoplasm itself, and thus Beale is fully justified 
in comprising both under the term "germinal matter." The nuclei control 
the nutrition of the cell, and probably initiate the process of subdivision. If 
a cell be mechanically divided so that a portion of it possesses the nucleus 
while other portions have no nucleus, that portion containing the nucleus will 
live and develop while the parts without nucleus soon die. Concerning this 
interesting question of the relation of the nuclei and cytoplasm in the cells, 
Schafer summarizes as follows: "There are cells and unicellular organisms 
both animal and vegetable, in which no reticular structure can be made out, 
and these may be formed of hyaloplasm alone. In that case, this must be 
looked upon as the essential part of protoplasm. So far as ameboid phenom- 
ena are concerned it is certainly so; but whether the chemical changes which 
occur in many cells are effected by this or by spongioplasm is another matter." 

Protoplasmic nuclei are highly differentiated chemically as well as func- 
tionally. They contain special structures which react in a characteristic 
chemical way to staining solutions, and to other chemical treatment. This 
differential structure is emphasized in Chapter II. There the morphological 
changes through which the nuclei pass in cell multiplication are given in 
greater detail. It is the study of these changes that supplies the basis of fact 
for many of our present conceptions of the physiological importance of 

Differentiation and Growth of Organized Protoplasm. The detail of cellu- 
lar division of protoplasm is more fully given in Chapter II. The morphologi- 
cal fact to which attention is called here is that as we proceed upward in the 
scale of life from the unicellular organisms, another phenomenon is exhibited 
in the life history of the higher forms, namely, that of development. The 
one-celled ameba comes into being derived from a previous ameba; it mani- 
fests the properties and performs the functions of its life which have been 
already enumerated. In the higher organisms it is different. Each, indeed, 
begins as a single cell, but the cells which result from division and subdivision 
do not form so many independent organisms but adhere in one differentiated 
community which ultimately forms the complex but co-ordinated whole, in 
man the human body. 

Thus from the ovum or germ cell which forms the starting-point of an 
individual animal during development, there is rapidly formed a number of 
tissues each characterized by its own type of structure, the whole laid down in 
an orderly manner to form the complicated individual. In the unfolding 
of this individual growth process, the developing ovum soon forms a complete 
membrane of cells called the blastoderm, and this speedily differentiates into 
two and then into three layers, chiefly from the rapid proliferation of the cells 
of the first single layer. These layers, figure 10, are called the Epiblast, the 
Mesoblast, and the Hypoblast. In the further development of the animal 



it is found that from each of these layers is produced a very definite part 'of 
the completed body. For example, from the cells of the epiblast are derived, 
among other structures, the skin and the central nervous system; from the 
mesoblast the muscles and connective tissue of the body, and from the 
hypoblast the epithelium of the alimentary canal, some of the chief glands, 
and so on. 

The result of this developmental process therefore is the formation of the 
adult tissues highly differentiated and specialized in form. 

From the physiologist's point of view this anatomical differentiation 
accomplishes a highly specialized structure which, machine-like, is capable of 
doing some part of the total work of the body in an especially effective manner. 
In a word, the differentiated tissues do not altogether lose the general proper- 
ties which characterize protoplasm, but each tissue develops a structure capa- 
ble of doing some special part of this activity better than the undifferentiated 
protoplasm can do it. As an illustration, the muscles, derived chiefly from 

FIG. 10. Transverse Section through Embryo Chick (26 hours), a, Epiblast; b, 
mesoblast; c, hypoblast; d, central portion of mesoblast, which is here fused with epiblast; 
e, primitive groove; /, dorsal ridge. (Klein.) 

either epithelial cells or mesoblast, are highly contractile, and especially 
responsive to stimuli. They have not developed in the same degree the power 
to produce chemical substances which characterizes the salivary glands. The 
cells of the liver, on the other hand, in the adult stage have practically lost the 
property of contractility, but have developed in a high degree the functional 
properties of nutrition and secretion. 

Hand in hand with the anatomical differentiation has gone physiological 
division of labor. In the adult animal body each type of activity is no longer 
accomplished by the whole organism as in the case of the ameba, but now 
some specializing part of the body assumes each chief activity. In other 
words the muscles contract, the nervous tissue conducts changes from one part 
of the body to the other, glands secrete, special sense organs respond to the 
stimuli of the environment, and the reproductive gonads have assumed the 
chief responsibility in the reproductive process. It is through the high 
degree of physiological division of labor that the great versatility of the body 
activity is accomplished by the human organism. It is a matter of great 
economy and effectiveness in this biological machine, the body. 



Differences between Animals and Plants. Having considered the 
vital properties of protoplasm, as shown in cells of animal as well as of vege- 
table organisms, we are now in a position to discuss the question of the differ- 
ences between plants and animals. It might at the outset of our inquiry have 
seemed an unnecessary thing to recount the distinctions which exist between 
an animal and a vegetable organism as they are in many cases so obvious, but, 
however great the differences may be between the higher animals and plants, 
in the lowest of them the distinctions are much less plain. 

In the first place, it is important to lay stress upon the differences between 
vegetable and animal cells, first as regards their structures and next as re- 
gards their functions. 

It has been already mentioned that in animal cells an envelope or cell wall 
is by no means always present. In adult vegetable cells, on the other hand, 
a well-defined wall is highly characteristic; this is composed of cellulose, 
is non-nitrogenous, and thus differs chemically as well as structurally from 
the contained protoplasmic mass. Moreover, in vegetable cells, figure n, 
B, the protoplasmic contents of the cell fall into two subdivisions: i, a con- 
tinuous film which lines the interior of the cellulose wall; and, 2, a reticulate 

FIG. ii. A. Young Vegetable Cells, Showing Cell Cavity Entirely Filled with Gran- 
ular Protoplasm Enclosing a Large Oval Nucleus, with one or more Nucleoli. B. Older 
cells from same plant, showing distinct cellulose wall and vacuolation of protoplasm. 

mass containing the nucleus and occupying the cell cavity. The inter- 
stices are filled with fluid. In young vegetable cells such a distinction does 
not exist; a finely granular protoplasm occupies the whole cell cavity, figure 
n, A. As regards the respective functions of animal and vegetable cells, 
one of the most important differences consists in the power which vegetable 
cells possess of being able to build up new complicated nitrogenous and 
non-nitrogenous bodies out of very simple chemical substances obtained 
from the air and from the soil. They obtain from the air oxygen, carbon 
dioxide, and water, as well as traces of ammonia gas; and from the soil they 
obtain water, ammonium salts, nitrates, sulphates, and phosphates in com- 
bination with such bases as potassium, calcium, magnesium, sodium, iron, 
and others. The majority of plants are able to work up these elementary 
compounds into other and more complicated bodies. This they are able 


to do in consequence of their containing a certain coloring matter called 
chlorophyll, the presence of which is the cause of the green hue of plants. 
In all plants which contain chlorophyll two processes are constantly going 
on when they are exposed to light: one, which is called true respiration and 
is a process common to animal and vegetable cells alike, consists in the 
taking of the oxygen from the atmosphere and the giving out of carbon 
dioxide; the other, which is peculiar apparently to bodies containing chloro- 
phyll, consists in the taking in of carbon dioxide and the giving out of oxygen. 
It seems that the chlorophyll is capable of decomposing the carbon dioxide 
gas and of fixing the carbon in the structures in the form of new compounds, 
one of the most rapidly formed of which is starch. 

Vegetable protoplasm by the aid of its chlorophyll is able to build up a 
large number of bodies besides starch, the most interesting and important 
being protein or albumin. It appears to be a fact that the power which 
plants possess of elaborate chemical synthesis is to a large extent dependent 
upon the chlorophyll they contain. Thus the power is present to a marked 
extent only in the plants in which chlorophyll is found, and is absent in 
those saphrophytic plants which do not possess chlorophyll. 

It must be recollected, however, that chlorophyll without the aid of the 
light of the sun can do nothing in the way of building up substances, and a 
plant containing chlorophyll when placed in the dark, while it continues to 
live, though not as a rule long, acts as though it did not contain any of that 
substance. It is an interesting fact that certain of the bacteria have the 
chlorophyll replaced by a similar pigment which is able to decompose carbon 
dioxide gas. 

Animal cells do not possess the power of building up or synthesizing from 
simple materials, though higher organic synthesis can no longer be ques- 
tioned. Their activity is chiefly exercised in the opposite direction, viz., the 
oxidations of the complicated compounds produced by the vegetable kingdom 
which they have brought to them as foods. With these foods animals are able 
to perform their complex functions, setting free energy in the direction of 
heat, motion, and electricity, and at the same time eliminating such bodies as 
carbon dioxide and water, and producing other bodies, many of which contain 
nitrogen but are derived from decomposition. 

With reference to the substance chlorophyll it has been noted that 'the 
synthetical operations of vegetable cells are peculiarly associated with the 
possession of chlorophyll and that these operations are dependent upon the 
light of the sun. It has been further shown that a solution of chlorophyll 
when examined with the spectroscope reveals a definite absorption spectrum, 
and that it is particularly those parts of the solar spectrum corresponding 
to these absorption bands which are chiefly active in the decomposition of 
carbon dioxide. In the synthetical processes of the plant, then, by aid of its 
chlorophyll, the radiant energy of the sun's rays becomes stored up or ren- 


dered potential in the chemical products formed. The potential energy is 
set free, or is again made kinetic, when these products by simple combustion 
produce heat, or when they are taken into the animal organism and used as 
food and there later produce heat and motion. 

The influence of light is not absolutely essential to animal life; indeed, 
it is said not to increase the metabolism of animal tissue to any great extent, 
and the animal cell does not receive its energy directly from the sun's light 
nor yet to any extent from the sun's heat, but from the potential energy of the 
food stuffs. But it must be always kept in mind that anabolism is not pecu- 
liar to vegetable, or katabolism to animal cells; both processes go on in each. 
Some of the lowest forms of vegetable life, e.g., the bacteria, will live only in a 
highly albuminous medium, and in fact seem to require for their growth 
elements of food stuffs which are essential to animal life. In their metabo- 
lism, too, they very closely approximate animal cells, not only requiring an 
atmosphere of oxygen, but giving out carbon dioxide freely, and secreting 
and excreting many very complicated nitrogenous bodies, as well as forming 
protein, carbohydrates, and fat, requiring heat but not light for the due per- 
formance of their functions. However, certain bacteria grow only in the 
absence of oxygen. 

There is, commonly, a difference in general chemical composition be- 
tween vegetables and animals, even in their lowest forms; for associated 
with the protoplasm of the former is a considerable amount of cellulose, a 
substance closely allied to starch and containing carbon, hydrogen, and 
oxygen only. The presence of starch in vegetable cells is very character- 
istic, though, as we have seen above, it is not distinctive, and a substance, 
glycogen, similar in composition to starch, is very common in the organs and 
tissues of animals. 

Inherent power of movement is a quality which we so commonly consider 
an essential indication of animal nature that it is difficult at first to conceive 
of its existence in any other. The capability of simple motion is now known, 
however, to exist in so many vegetable forms that it can no longer be held 
as an essential distinction between them and animals, and ceases to be a mark 
by which one can be distinguished from the other. Thus the zoospores of 
many of the Cryptogams exhibit ciliary or ameboid movements of a like 
kind to those seen in amebae; and even among the higher orders of plants, 
many, e.g.,Dioncca muscipula (Venus's fly-trap), and Mimosa sensitiva (Sensi- 
tive plant) exhibit such motion, either at regular times or on the applica- 
tion of external irritation. Were this fact taken by itself, it might lead one to 
regard them as sensitive organisms. Inherent power of movement, then, 
although especially characteristic of animal nature, is, when taken by itself, 
no proof of it. 

Sources and Utilization of Physiological Material. In studying the 
functions of the human body it is necessary first of all to know of what it is 


composed, of what tissues and organs it is made up; this can of course be 
ascertained only by the dissection of the dead body, and thus it comes that 
Anatomy, the science which treats of the structure of organized bodies, is 
closely associated with physiology, which treats of the functions of these 
structures. So close, indeed, is the association that Histology, which is 
especially concerned with the minute or microscopic structure of the tissues 
and organs of the body and which is, strictly speaking, a department of 
anatomy, is often included in works on physiology. There is much to be 
said in favor of such an arrangement, since it is impossible to consider the 
changes which take place in any tissue during life, apart from the knowledge 
of the structure of the tissues themselves. There is indeed an almost insep- 
arable relation between the structure and the function of the differentiated 
animal body in which the one is made the means to a knowledge of the other 
as an end, and vice versa, according to the aims and purposes of the student. 

An equally important essential to the right comprehension of the changes 
which take place in the living organism is a knowledge of the chemical com- 
position of the body. Here, however, we can deal directly only with the 
composition of the dead body, and it is well at once to admit that there may 
be many chemical differences between living and non-living tissues; but as it 
is impossible to ascertain the exact chemical composition of the living tissues, 
the next best thing which can be done is to find out as much as possible about 
the composition of the same tissues after they are dead. This is the assist- 
ance which the science of Chemistry can afford to the physiologist. 

Having considered the structure and composition of the body, we' are 
brought face to face with physiology proper, and have to investigate the vital 
changes which go on in the tissues, the various actions taking place as long 
as the organism is at work. The subject includes not only the observation 
of the manifest processes which are continually taking place in the healthy 
body, but the conditions under which these are brought about, the laws 
which govern them and their effects. 

It may be well to mention as a preliminary that the physiological informa- 
tion which we have at our disposal has been derived from many sources, the 
chief of which are as follows: i, From actual observation of the various 
phenomena occurring in the human body from day to day, and from hour to 
hour, as, for example, the estimation of the amount and composition of the 
ingesta and egesta, the respiration, the beat of the heart, and the like; 2, from 
observations upon other animals, the bodies of which we are taught by com- 
parative anatomy approximate the human body in structure, and may be 
supposed to be similar in function; 3, from observations of the changes 
produced by experiment upon the various processes in such animals, or in the 
organs and tissues of animals; 4, from observations of the changes in the 
working of the human body produced by diseases; and 5, from observations 
upon the gradual changes which take place in the functions of organs when 


watched in the embryo from their earliest beginnings to their completed 

The physiologist, in order to utilize the sources of material, must be 
familiar with the gross structure of the animals or parts of animals which he 
proposes to use in experimental procedure. So simple a matter as the deter- 
mination of arterial blood pressure involves familiarity with extensive ana- 
tomical structure. Experimental procedure must also draw on the field of 
microscopic structure or histology, and many of the most instructive bodies of 
physiological knowledge have come directly from the utilization of the facts 
of comparative anatomy and of biology. The problems in animal nutrition 
which are under such extensive investigation at the present time require for 
their solution not only the use of the most complex methods of chemistry, 
both analytic and synthetic, but also the principles and methods of physics. 
Indeed, since the work of Helmholz, the interpretation of physiological phe- 
nomena by means of physical methods and laws has contributed more than 
any other means toward the prominent scientific position of physiology at the 
present time. In a word, physiology must utilize the facts of anatomy, his- 
tology, biology, physics, and chemistry to interpret the phenomena of life. 



In the preceding discussion a general view of the type of cell activity and 
the structural basis therefor has been briefly presented. Emphasis has been 
laid on the fact that the complicated phenomena of life are manifested through 
the agency of the tissues and cells. The histological cells, alone or in com- 
bination, are capable of all the activities manifested by the living body. 
Throughout the different phases of the physiological discussions which follow 
it will be assumed that the reader has some knowledge of this structural basis. 
However, for the purpose of reference there is presented in this chapter a 
brief but elementary review of the characteristic cytological structure of the 
tissues and cells of the animal body. 


The typical cell is a spherical or ovoid mass of protoplasm. It is of 
microscopic size and varies from 6 or 7 micra in diameter for the lymphocytes 
and erythrocytes to 150 to 200 micra for the diameters of the larger cell 
bodies of the neurones. Its structure is quite complex, but the most general 
differentiation is into the cell-mass or cytoplasm, and its contained nucleus. 
The cytoplasm is sometimes bounded by a definite cell membrane, but in 
differentiated animal tissues this membrane is usually not present. 

The Cell Body. The cell body or ctyoplasm is a complex semi-fluid mass, 
the determination of the detailed relations of which has presented many 
difficulties. The cell cytoplasm is usually described as having a framework 
of spongioplasm supporting a homogeneous hyaloplasm. In some cells there 
are formed materials resulting from the cellular activity called metaplasm, 
figure 12. 

Cell protoplasm includes several kinds of stainable granules and fibrils, 
some are essential constituents while others are formed by the reactions of the 
protoplasm and are in a sense extraneous material. These structural 
features are made more evident by their selective affinity for certain staining 

The exact form of the spongioplasm or reticulum varies greatly in different 
types of cells, and even in different parts of the same cell. Its affinity for 
stains discloses a fine network, the reticulum, which increases in amount 
and also in constancy in the type of arrangement in the older cells. 




The hyaloplasm is more fluid, less refractile, and stains with great diffi- 
culty. It fills the interspaces of the spongioplasm. In this material may 
be embedded such substances as the metaplasts mentioned above. 

The hyaloplasm contains in solution the various nutritive constituents 
brought to the cell as well as the soluble end products of its chemical activity. 
Here, too, are found the various hormones, oxidases and enzymes which 
play so important a part in the cellular reactions in the different types of cells. 

Structure of the Nucleus. The nucleus when in a condition of rest 
is bounded by a distinct membrane, the nuclear membrane, possibly derived 
from the spongioplasm of the cell, which encloses the nuclear contents, nucleo- 
plasm or karyoplasm. The membrane consists of an inner, or chromatic, 
and of an outer, or achromatic layer, so called from their reaction to stains. 
The nucleoplasm is made up of a reticular network, or chromoplasm, whose 
interspaces are filled by the karyolymph, or nuclear matrix, a homogeneous 
substance which is rich in proteins, has but slight affinity for stains, and is 
supposed to be fluid in consistency. 

Cell membrane. 

Metaplasmic gran- < --'* 

Karyosome or net- '--'< 




Linin network. 

. Attraction sphere. 


., Plastids. 

'-.C\ - - \--^,-~- V- .- ----- Chromatin . 

--:--r--.?V --"->-> Nuclear membrane. 

- Nucleolus. 
\----s-~~jf--. __ Vacuole. 

FIG. 12. Diagram of a Typical Cell. (Bailey.) 

The network is composed of linin or achromatin, a transparent unstain- 
able framework, and of chromatin, which stains deeply. It is supported by 
the linin, and occurs sometimes in the form of granules, but usually as irreg- 
ular anastomosing threads, both thicker primary fibers and thinner connect- 
ing branches. The threads often form thickened nodes, karyosomes or 
false nucleoli, at their points of intersection. It is now quite generally be- 
lieved that the chromatin occurs as short, rod-like, and highly refractive 
masses, which are embedded in the linin in a regular series. 

The nucleoli, or plasmosomes, are spherical bodies which stain deeply, and 
may either lie free in the nuclear matrix or be attached to the threads of 
the network. 


The Centrosome and Attraction Sphere. In addition to the nucleus, 
a minute spherical body called the centrosome is believed to be constantly 
present in animal cells, though sometimes too small to be demonstrated. 
The centrosome is smaller than the nucleus, close to which it lies, and exerts a 
peculiar attraction for the protoplasmic filaments and granules in its vicinity, 
so that it is surrounded by a zone of fine radiating fibrils, forming the attrac- 
tion sphere or archoplasm. Some authorities assert that the centrosome 
lies within the nucleus in the resting state, and passes into the cell proper only 
in the earlier stages of cell division. The attraction sphere is most distinctly 
seen in cells about to divide. It plays an important role in nuclear division, 
but it is doubted if it gives the initial impulse to the process. 

Cell Multiplication. Cells increase in number by a process known 
as cell division, of which the first act is nuclear division. In fact the nucleus 
is the center of control of the cell mass in the process of division. Cell multi- 
plication takes place by two recognized methods, direct or amitosis, in which 
there is little disturbance of the nuclear network, and indirect or mitosis, in 
which there is a complex series of nuclear network changes. 


FIG. 13. Akinesis, Amitosis, or Direct Cell Division. A, Constriction of nucleus; B, 
division of nucleus and constriction of cell body; C, daughter nuclei still connected by a 
thread, division being delayed; D, division of cell body nearly complete. (After Arnold.) 

Direct Cell Division or Amitosis. The division of a cell is preceded 
by division of its nucleus. Direct or simple division, amitosis or akinesis, see 
figure 13, occurs without any change in the arrangement of the intranuclear 
network. A constriction develops at the center of the nucleus, possibly pre- 
ceded by division of the nucleoli, and gradually divides it into two equal 
daughter nuclei. A similar constriction of the protoplasm of the cell occurs 
between the daughter nuclei and divides it into two parts. 

Indirect Cell Division or Mitosis. Indirect division, mitosis, orkaryo- 
kinesis is the usual method of cell division, and consists of a series of changes 
in the arrangement of the intranuclear network, resulting in the exact division 



of the chromatic fibers into two parts, which form the chromoplasm of the 
daughter nuclei. The changes follow a closely similar course in both plant 
and animal cells. 

The process may be divided into the following 

Prophase. The resting nucleus becomes somewhat 
enlarged, and the centrosome (according to those who 
regard it as lying normally within the nucleus) migrates 
into the cell protoplasm. The centrosome then divides 
into two daughter centrosomes which lie near the nucleus 
but are separated by a considerable interval. Each is 
surrounded by the radiating fibrils of the attraction 
sphere, and some of these fibrils pass continuously from 
one centrosome to the other, forming the achromatic 
spindle. At the same time the intranuclear network be- 
comes converted into a fine convoluted coil, the spirem or 
skein, which may be either continuous or else broken up 
into several threads. The thread or threads then 
shorten and become thicker, while the convolutions, 
which have become less numerous, arrange themselves in a series of 
connecting loops, forming the wreath. The nuclear membrane and the 
nucleolus disappear, the latter passing at times into the cell protoplasm and 
disintegrating. The wreath then breaks up into V-shaped segments, the 
chromosomes, of which each species of animal has a constant and character- 
istic number. This varies in the different animals, but is sixteen in man. 

The two centrosomes migrate to the poles of the nucleus, while the achro- 
matic spindle which connects them occupies the long axis of the nucleus 

FIG. 14. Leuco- 
cyte of Salamander 
Larva, Showing At- 
traction Sphere. 
(After Flemming.) 

FIG. 15. Early Stages of Karyokinesis. A. The thicker primary fibers remain and 
the achromatic spindle appears. B. The thick fibers split into two and the achromatic 
spindle becomes longitudinal. (Waldeyer.) 

The chromosomes, becoming much shorter and thicker, gather around the 
spindle in its equatorial plane, with their angles directed toward the center, 
forming the aster or monaster. 

Metaphase. The actual division of the nucleus is begun at this time by the 
splitting of each chromosome longitudinally into halves which lie at first close 
together so that each seems doubled. Soon afterward the fibrils of the 



achromatic spindle begin to contract, and thus separate the halves of the 
chromosomes in such a way that one-half of each is turned toward one pole, 
and the other half toward the other. As this continues, the two groups, 
which are equal in size, draw away from each other and from the equator, 
each group being formed of daughter chromosomes. 

FIG. 1 6. Monaster Stage of Karyokinesis. (Rabl.) 

Anaphase. The two groups (daughter chromosomes) now gradually ap- 
proach their respective poles, or centrosomes, and the equator becomes free. 
On reaching the pole, each group gathers in a form which is similar in arrange- 
ment to the monaster and is known as the diaster. During this time the cell 
body becomes slightly constricted by a circular groove at its equatorial plane. 

Telophase. Soon afterward the fibrils of the chromatic spindle which 
connect the two groups begin to grow dim and finally disappear. The daugh- 

FIG. 17. Stages of Karyokinesis. A. Commencing separation of the split chromo- 
somes. B. The separation further advanced. C. The separated chromosomes passing 
along the fibers of the achromatic spindle. (Rabl.) 

ter chromosomes assume the form of threads twisted in a coil and develop 
each a nuclear membrane and a nucleolus, forming a daughter nucleus. 
The nuclei enlarge and the nuclear threads assume the appearance of the 
resting state of the nucleus. Meanwhile, the constriction about the body 
of the cell cytoplasm has become deeper and deeper until the protoplasm is 
divided into two equal parts, or daughter cells, each with its daughter nucleus, 
and the process of karyokinesis is completed. 



The Cell Types. All of the elementary tissues consist of cells and of 
their altered equivalents. It will be as well therefore to indicate some of the 
differences between the cells of the body. They are named in various ways, 
according to their shape, origin, and functions. 

Line of division "^| 

of cells. 

Antipole of daughter ' 

Remains of spindle. 

"'--> Lighter substance 
--'~"" of nucleus. 

Cell protoplasm. 

FIG. 1 8. Final Stages of Karyokinesis. In the lower figure the changes are still more 
advanced than in the upper. (Waldeyer.) 

From their shape, cells are described as spherical or spheroidal, which is 
the typical shape of the free cell; this may be altered to polyhedral when the 
pressure on a mass of cells in all directions is nearly the same; of this the 
primitive segmentation cells afford an example. The discoid form is seen 

FIG. 19. Karyokinesis, Mitosis, or Indirect Cell Division (diagrammatic). A, Cell 
with resting nucleus; B, wreath, daughter centrosomes and early stage of achromatic 
spindle; C, chromosomes; D, monaster stage, achromatic spindle in long axis of nucleus, 
chromosomes dividing; E, chromosomes moving toward centrosomes; F, diaster stage, 
chromosomes at poles of nucleus, commencing constriction of cell body; C, daughter nuclei 
beginning return to resting state; H, daughter nuclei showing monaster and wreath; 7, 
complete division of cell body into daughter cells whose nuclei have returned to the resting 
state. (After Bohm and von Davidoff.) 

in blood corpuscles, and the scale-like form in superficial epithelial cells. 
Some cells have a jagged outline and are then called prickle cells. Cells of 
cylindrical, conical, or prismatic form occur in various places in the body. 
Such cells may taper at one or both ends into fine processes, in the former case 


being caudate, in the latter fusiform, or they may be greatly elongated so as to 
become fibers. Cells with hair-like processes, or cilia, projecting from their 
free surfaces, are a special variety. The cilia vary greatly in size, and may 
even exceed in length the cell itself. Finally, cells may be branched or stellate 
with long outstanding processes. 

From theirfunction cells are called secreting, protective, sensitive, contractile, 
and the like. 

From their origin cells are called epiblastic and mesoblastic and hypoblastic, 
ectodermic, mesodermic, and endodermic. 

Modes of Cell Connection. Cells are connected together to form tissues 
in various ways. They are connected by means of a cementing intercellular 
substance. This is probably always present as a transparent, colorless, viscid, 
albuminous substance, even between the closely apposed cells of epithelium; 
while in the case of cartilage it forms the main bulk of the tissue, and the cells 
only appear as embedded in, not as cemented together by, the intercellular 
substance. This intercellular substance may be either homogeneous or 
fibrillated. In many cases, e.g., the cornea, it can be shown to contain a 
number of irregular branched cavities, which communicate with each other, 
and in which branched cells lie. Nutritive fluids can find their way through 
these branching spaces into the very remotest parts of a non-vascular tissue. 
The basement membrane, membrana propria must be mentioned as a special 
variety of intercellular substance which is found at the base of the epithelial 
cells in most mucous membranes, and especially as an investing tunic of 
gland follicles which determines their shape. 

Cells are connected by anastomoses of their processes. This is the usual 
way in which stellate cells, e.g., of the cornea, are united. The individuality 
of each cell is thus to a great extent lost by its connection with its neighbors 
to form a reticulum. As an example of a network so produced we may cite 
the anastomosing cells of the reticular tissue of lymphatic glands. 

The intercellular substance sometimes forms so great a part of the tissue 
as to overshadow the cells proper. Examples of this type of structure are 
found in the matrix of cartilage, the fibers of connective tissue, bone, etc. 

Decay and Death of Cells. There are two chief ways in which the 
comparatively brief existence of cells is brought to an end, i.e., by mechanical 
abrasion and by chemical transformation. 

The various epithelia furnish abundant examples of mechanical abrasion. 
As it approaches the free surface, the epidermal cell becomes more and more 
flattened and scaly in form and more horny in consistency, till at length it is 
simply rubbed off. Hence we find free epithelial cells in the mucus of the 
mouth, in the intestine, and in the genito-urinary tract, as well as on the sur- 
face of the outer skin. 

In the case of chemical transformation the cell contents undergo a 
degeneration which, though it may sometimes be pathological, is very often 


a normal process. Thus we have cells by fatty metamorphosis producing 
oil globules in the secretion of milk, fatty degeneration of the muscular fibers 
of the uterus after the birth of the fetus. Calcareous degeneration is common 
in the cells of many cartilages. 

As the cells approach decay and death their normal physiological processes 
diminish in intensity and finally cease. This occurs early in the transforma- 
tion and function is lost before the cell form is destroyed beyond recognition. 


In the differentiation of the protoplasm of the body, great masses of 
cells are formed of the same elemental structure and typical functional prop- 
erties. These are the elementary tissues. The tissues alone or in combina- 
tion in varying proportions constitute the organs of the body. These ele- 
mentary tissues are: The Epithelial, The Connective, The Muscular, and The 
Nervous Tissues. To these four some would add a fifth, looking upon the 
Blood and Lymph, containing, as they do, formed elements in a fluid men- 
struum, as a distinct tissue. 


Epithelium is a tissue composed almost wholly of cells, with a very 
small amount of intercellular substance which glues the cells together. 
In general it includes all those cellular membranes which cover either an 
external or an internal free surface, together with the cellular portions of the 
glands which are connected with, or developed from, these free surfaces. 

Epithelium clothes (i) the whole exterior surface of the body, forming 
the epidermis with its appendages; becoming continuous at the chief orifices 
of the body nose, mouth, anus, and urethra with (2) the epithelium which 
lines the whole length of the respiratory, alimentary, and genito-urinary 
tracts, together with the ducts and secretory cells of their various glands. 
Epithelium also lines the cavities of (3) the brain and the central canal of the 
spinal cord, (4) the serous and synovial membranes, and (5) the interior of 
blood vessels and lymphatics. 

Epithelial cells vary in size and shape, pressure being the main factor in 
this variation. The protoplasm may be granular, reticular, or fibrillar in 
appearance. The nucleus is spherical or oval, usually there is only one, but 
there may be two or more present. 

Epithelial tissues are non-vascular, that is to say, do not contain blood 
vessels, but in some varieties minute channels exist between the cells of 
certain layers. Nerve fibers are supplied to the cells of many epithelia. 

As to form and arrangement of cells. 

I. Epithelia in the form of membranes (covering surfaces), 
i. Simple epithelium. Cells only one layer in thickness. 


(1) Squamous or pavement. Cells flattened. 

(a) Non-ciliated. Alveoli of lungs, also includes endothelium, 
lining the blood vessels, and mesothelium, lining the large 
serous spaces. 

(b) Ciliated. The peritoneum of some forms at breeding season. 

(2) Cubical epithelia. Cells with the three dimensions approxi- 

mately equal, mainly glandular. 

(a) Non-ciliated. The usual type. It is found lining both 
ducts and secretory portions of most glands, the pigmented 
layer of the retina, etc. 

(b) Ciliated. Not common. Lining of some of the smaller 
bronchial tubes. 

(3) Columnar. Cells may be cylindrical, conical, or goblet-shaped. 

(a) Non-ciliated. Intestinal. 

(b) Ciliated. Fallopian tube and uterus. 

(c) Pseudo-stratified. Smaller bronchi, nasal duct, etc. 
2. Stratified epithelia. Cells more than one layer in thickness. 

(1) Squamous. Surface cells flattened. 

(a) Non-ciliated. Skin, mouth, vagina, etc. 

(b) Ciliated. Pharynx of embryo. 

(2) Columnar. Surface cells columnar. 

(a) Non-ciliated. Portions of male urethra. 

(b) Ciliated. Trachea, bronchi, etc. 

II. Epithelia not in the form of membranes, but in solid masses or cords, 
usually glandular. 

(1) Cells spheroidal. Ova. 

(2) Cells polyhedral. Liver, suprarenal, etc. 
Epithelia, classified mainly as to function. 

I. Protective. Skin, mouth, alimentary canal. 

1. Cornified. Skin, nails, hair. 

2. Cuticular border. Columnar cells of intestine. 
II. Glandular. 

1. Secretory. Cells of salivary glands, pancreas, etc. 

2. Excretory. Cells of kidney. 

3. Absorptive. Cells of alimentary canal. 

III. Sensory Epithelium. Cells of olfactory membrane, organ of Corti, 

taste buds, etc. 

IV. Reproductive. Sex cells. 

V. Pigmented. Pigmented layer of retina. 
VI. Ciliated. Trachea, uterus, Fallopian tube, etc. 
Only a few of the more important of the above-mentioned types of epithe- 
lium will be described here. 

Simple Epithelium. Simple Squamous. This form of epithelium 


is found arranged in a single layer of flattened cells, for example, the lining of 
the alveoli of the lungs and of the descending arm of Henle's loop of the 
kidney tubule. Aside from endothelium as mesothelium it has very limited 
distribution in man. Endothelium and mesothelium are typical simple 
.squamous epithelia. They consist of much flattened cells with clear or 
.slightly granular protoplasm and oval bulging nuclei, the edges of the cells 
.are peculiarly wavy or serrated. 

FIG. 20. The Endothelium of a Small Blood Vessel. Silver-nitrate stain. X 350. 

The presence of endothelium in any locality may be demonstrated by 
staining with silver nitrate, which brings into view the intercellular cement 
substance. When a small portion of a perfectly fresh serous membrane, 
for example, figure 20, is immersed for a few minutes in a solution of silver 
nitrate, and exposed to the action of light, the silver is precipitated in the in- 
tercellular cement substance, and the endothelial cells are thus mapped out 
by fine, dark, and generally sinuous lines of extreme delicacy. 

FIG. 21. Abdominal Surface of Central Tendon of the Diaphragm of Rabbit, showing the 
general polygonal shape of the endothelial cells; each cell is nucleated. (Klein.) X 300. 

Endothelial cells in certain situations may be ciliated, e.g., those of the 
mesentery of the frog, especially during the breeding season. 

On those portions of the peritoneum and other serous membranes in 
which lymphatics abound, apertures, figure 22, are found surrounded by 
small, more or less cubical, cells. These apertures are called stomata. They 
are particularly well seen in the anterior wall of the great lymph sac of the 
frog, figure 22, and in the omentum of the rabbit. These are really the open 
mouths of lymphatic vessels or spaces, and through them lymph corpuscles 
and the serous fluid from the serous cavity pass into the lymphatic system. 


Simple Non-ciliated Columnar Epithelium, figure 23, lines, a, the mucous 
membrane of the stomach and intestines as a single layer, from the cardiac 
orifice of the stomach to the anus, and b, wholly or in part all the ducts of the 
glands opening on its free surface, and c, many gland ducts in other regions 
of the body, e.g., mammary, salivary, etc. The intracellular and intra- 

FiG. 22. Peritoneal Surface of a Portion of the Septum of the great Lymph Sac of Frog. 
The stomata, some of which are open, some collapsed, are surrounded by endothelial cells 
Klein.) X 160. 

nuclear networks are well developed, and in some cases the spongioplasm is 
arranged in rods or longitudinal striae at one part of the cell, as in the cells of 
the ducts of salivary glands. The protoplasm of columnar cells may be 
vacuolated and may also contain fat or other substances seen in the form of 
granules. Certain columnar cells transform a large part of their protoplasm 

FIG. 23. Simple Columnar Epithelial Cells from the Human Intestinal Mucous 
Membrane, a, Mucous (goblet) cell; b, basement membrane; c, cuticle; d, leucocyte 
nucleus; e, germinating cell. (Bailey.) 

into mucin, goblet cells, figure 24, which is discharged by the open mouth 
of the goblet, leaving only a nucleus surrounded by the remains of the proto- 
plasm in its narrow stem. This transformation is a normal process which 
is continually going on during life, the cells themselves being supposed to 
regenerate into their original shape. 

Stratified Epithelium. The term stratified epithelium is employed 



to describe the type found in the skin or its derivatives in which the cells 
forming the epithelium are arranged in a considerable number of superim- 
posed layers. The shape and size of the cells of the different layers, as well 
as the number of layers, vary in different situations. Thus the superficial 
cells may be either squamous or columnar in shape and the deeper cells 
range from polygonal to columnar in form. 

FIG. 24. FIG. 25. 

FIG. 24. Goblet Cells. (Klein.) 

FIG. 25. Cross-section of a Villus of the Intestine, e, Columnar epithelium with 
striated border; g, goblet cell, with its mucus partly extruded; /, lymph corpuscles between 
the epithelial cells; &, basement membrane; c, sections of blood capillaries; m, section of 
plain muscle fibers; c I, central lacteal. (Schafer.) 

Stratified Squamous. The intermediate cells are polygonal in shape and 
approach more to the flat variety the nearer they are to the surface, and to the 
columnar as they approach the lowest layer. In many of the deeper layers 
of epithelium in the mouth and skin, the outline of the cells is very irregular, 
in consequence of processes passing from cell to cell across these intervals. 
Such cells, figure 28, are termed "prickle" cells. These "prickles" are the 

FlG. 26. Squamous Epithelium Scales from the Inside of the Mouth. X 260. (Henle.) 

intercellular bridges which run across from cell to cell, the interstices being 
filled by the transparent intercellular lymph. When this increases in quan- 
tity in inflammation the cells are pushed further apart, and the connecting 
fibrils or "prickles" are elongated and more clearly visible. 

The columnar cells of the deepest layer are distinctly nucleated; they 
multiply rapidly by division; and as new cells are formed beneath, they press 
the older cells forward, to be in turn pressed forward themselves toward the 


2 9 

surface, gradually altering in shape and chemical composition until they 
die and are cast off from the surface. 

Stratified squamous epithelium is found in the following situations: i. 
Forming the epidermis, covering the whole of the external surface of the body; 
2. Covering the mucous membrane of the nose, tongue, mouth, pharynx, and 
esophagus; 3. As the conjunctival epithelium, covering the cornea; 4. 
Lining the vagina and the vaginal part of the cervix uteri. 

FIG. 27. Vertical Section of the Stratified Epithelium Covering the Front of the 
Cornea. Highly magnified. (Schafer.) c, Lowermost columnar cells; p, polygonal cells 
above these ; fl, flattened cells near the surface. The intercellular channels, bridged by 
minute cell processes, are well seen. 

Stratified Columnar Epithelium. In this type of epithelium, the surface 
cells alone are columnar, the deeper cells being irregular in shape. From 
the surface cells long processes extend down among the underlying cells. 
This type of epithelium is usually ciliated, as in the trachea, bronchi, etc., 
but may be non-ciliated, as in portions of the human male urethra. 


FIG. 28. Epithelial Cells from the Stratum Spinosum of the Human Epidermis, Showing 
"Intercellular Bridges." X 700. (Szymonowicz.) 

Transitional Epithelium. This is a stratified epithelium consisting of 
only three or four layers of cells. The superficial cells are large and flat, 
often containing two nuclei. The under surfaces of these cells are hollowed 
out, and into these depressions fit the large ends of the pyriform cells which 
form the next layer. Beneath the layer of pyriform cells are from one to 


four layers of polyhedral cells. This type of epithelium occurs in the bladder, 
ureter, and pelvis of the kidney. 

Specialized Epithelium. Glandular epithelium forms the active secreting 
agent in the glands; the cells are usually spheroidal, but may be polyhedral 
from mutual pressure, or even columnar; their protoplasm is generally oc- 
cupied by the materials which the gland secretes. Examples, of glandular 

FIG. 29. Stratified Columnar Ciliated Epithelium from the Human Trachea. 

(goblet) cell also is present. 

A mucous 

epithelium are to be found in the liver, figure 31, in the secreting tubes of 
the kidney, and in the salivary, figure 32, and gastric glands. 

Ciliated epithelium consists of cells which are generally cylindrical in form, 
figures 29, 30, but may be spheroidal or even squamous. 

This form of epithelium lines: a. The mucous membrane of the respira- 
tory tract beginning just beyond the nasal aperture, and completely covers 
the nasal passages, except the upper part to which the olfactory nerve is 



FIG. 30. Transitional Epithelium from the Human Bladder. (Bailey.) 

distributed, and also the sinuses and ducts in connection with it and the 
lachrymal sac, the upper surface of the soft palate and the naso-pharynx, 
the Eustachian tube and tympanum, the larynx, except over the vocal cords, 
to the finest subdivisions of the bronchi. In part of this tract, however, 
the epithelium is in several layers, of which only the most superficial is ciliated, 


so that it should more accurately be termed transitional, page 24, or stratified. 
b. Some portions of the generative apparatus in the male, viz., lining the 
vasa efferentia of the testicle, and their prolongations as far as the lower 

FIG. 31. 

FIG. 32. 

FIG. 31. A Small Piece of the Liver of the Horse. (Cadiat.) 

FIG. 32. Glandular Epithelium. Small lobule of a mucous gland of the tongue, 
showing nucleated glandular cells. X 200. (V. D. Harris.) 

end of the epididymis, and much of the vas deferens; in the female, c, com- 
mencing about the middle of the neck of the uterus, and extending throughout 
the uterus and Fallopian tubes to their fimbriated extremities, and even for 

FIG. 33. Specialized Pigmented Epithelial Cells of Retina. 

a short distance on the peritoneal surface of the latter, d. The ventricles of 
the brain and the central canal of the spinal cord are clothed with ciliated 
epithelium in the child, but in the adult this epithelium is limited to the cen- 
tral canal of the cord. 

The cilia themselves are fine rounded or flattened homogeneous processes. 

3 2 


According to some observers, these processes are connected with longitudinal 
fibers which pass to the other end of the cell, but which are not connected 
with the nucleus. 

FIG. 34. FIG. 35. 

FIG. 34. Spheroidal Ciliated Cells from the Mouth of the Frog. X 300 diameters. 

FIG. 35. Ciliated Epithelium from the Human Trachea, a, Large, fully formed cell; 
ft, shorter cell; c, developing cells with more than one nucleus. (Cadiat.) 

Functions of Epithelium. According to function, 
epithelial cells may be classified as: i, protective, e.g., in 
the skin, mouth, blood vessels, etc.; 2, protective and motive, 
ciliated epithelium; 3, secreting, glandular epithelium; 4, 
germinal, as epithelium of testicle producing spermatozoa; 
5, absorbing and secreting, e.g., epithelium of intestine; 6, 
sensory, e.g., olfactory cells, organ of Corti. 

Epithelium forms a continuous smooth investment 
over the whole body, being thickened into a hard, horny 
tissue at the points most exposed to pressure, and develop- 
ing various appendages, such as hairs and nails. Epithe- 
lium lines also the sensorial surfaces of the eye, ear, nose, 
and mouth, and thus serves as the medium through which 
all impressions from the external world touch, smell, 
taste, sight, hearing reach the delicate nerve endings, 
whence they are conveyed to the brain. 

The ciliated epithelium which lines the air passages 
serves to promote currents of the air in the bronchial tubes 
and to propel fluids and minute particles of solid matter 
out of the body. In the case of the Fallopian tube, the 
cilia assist the progress of the ovum toward the cavity of 
the uterus. 

The epithelium of the various glands, and of the 
(En- whole intestinal tract, has the power of secretion, i.e., of 

FIG. 36. Cili- 
ated Cell of the 
Intestine of a 


producing certain 

ism in its protoplasm. 

materials by processes of metabol- 


Epithelium is likewise concerned in the processes of transudation, 
diffusion, and absorption. 


This group of tissues forms the skeleton with its various connections 
bones, cartilages, and ligaments and also affords a supporting framework 
and investment to the various organs composed of nervous, muscular, and 
glandular tissue. Its chief function is the mechanical one of support, and 
for this purpose it is so intimately interwoven with nearly all the textures of 
the body that if all other tissues could be removed, and the connective tissues 
left, we should have a wonderfully exact model of almost every organ and 
tissue in the body. 

General Structure of Connective Tissue. The connective tissue is 
made up of two chief elements, namely, cells and intercellular or formed 

FIG. 37. Horizontal Preparation of the Cornea of Frog, Stained in Gold Chloride; 
showing the network of branched corneal corpuscles. The ground substance is completely 
colorless. X 400. (Klein.) 

Cells. The cells are usually of an oval shape, often with branched 
processes, which are united to form a network. They are most readily 
observed in the cornea, in which they are arranged, layer above layer, parallel 
to the free surface. They lie in spaces in the intercellular or ground sub- 
stance, which form by anastomosis a system of branching canals freely 
communicating, figure 37. 

The flattened tendon corpuscles which are arranged in long lines or rows 
parallel to the fibers belong to this class of cells, figure 39. 

These branched cells often contain pigment granules, giving them a dark 
appearance; they form one variety of pigment cell. Pigment cells of this 
kind are found in the outer layers of the choroid. In many of the lower ani- 



mals, such as the frog, they are found widely distributed not only in the skin, 
but also in internal parts, the mesentery, sheaths of blood vessels, etc. Under 
the action of light, electricity, and other stimuli, the pigment granules become 
massed in the body of the cell, leaving the processes quite hyaline; if the 
stimulus be removed, they will gradually be distributed again throughout 
the processes. Thus the skin in the frog is sometimes uniformly dusky and 
sometimes quite light colored, with isolated dark spots. 

Intercellular Substance. This isjibrillar, as in the fibrous tissues and in 
certain varieties of cartilage; or homogeneous, as in typical mucoid tissue. 

The fibers composing the former are of two kinds, white fibrous and 
yellow elastic tissue. 

FIG. 38. 

FIG. 38. Mature White Fibrous Tissue of Tendon, Consisting Mainly of Fibers with a 
Few Scattered Fusiform Cells. (Strieker.) 

FIG. 39. Caudal Tendon of Young Rat, Showing the Arrangement, Form, and 
Structure of the Tendon Cells. X 300. (Klein.) 

The chief varieties of connective tissues may be thus classified: 

White fibrous. 




Adenoid or retiform. 




1. Hyaline. 

2. White fibrous. 

3. Elastic. 
Bone and dentine. 

The White Fibrous Tissue. It is found typically in tendon; also in 
ligaments, in the periosteum and perichondrium, the dura mater, the peri- 



cardium, the sclerotic coat of the eye, the fibrous sheath of the testicle, in the 
fasciae and aponeuroses of muscles, and in the sheaths of lymphatic glands. 

Structure. To the naked eye, tendons and many of the fibrous mem- 
branes, when in a fresh state, present an appearance as of watered silk. 
This is due to the arrangement of the fibers in wavy parallel bundles. Under 
the microscope the tissue appears to consist of long, often parallel, bundles 
of fibers of different sizes. The cells in tendons, figure 39, are arranged 
in long chains in the ground substance separating the bundles of fibers, and 
are more or less regularly quadrilateral with large round nuclei containing 
nucleoli, generally placed so as to be contiguous in two cells. Each of 
these cells consists of a thick body from which processes pass in various 
directions into, and partially fill up the spaces between, the bundles of 
fibers. The rows of cells are separated from one another by lines of cement 

Yellow Elastic Tissue. Yellow elastic tissue is found chiefly in the 
ligamentum nuchae of the ox, horse, and other animals; the ligamenta sub- 
flava of man; the arteries, constituting the fenestrated coat of Henle; the 
veins in the lungs and trachea; the stylo-hyoid, thyro-hyoid, and crico- 
thyroid ligaments; in the true vocal cords; and in areolar tissue. 

Structure. Elastic tissue occurs in various forms, from a structureless, 
elastic membrane to a tissue whose chief constituents are bundles of fibers 
crossing each other at different angles; when seen in bundles elastic fibers are 
yellowish in color, but individual fibers are not 
so distinctly colored. The varieties of the tissue 
may be classified as follows: 

a. Fine elastic fibrils, which branch and anas- 
tomose to form a network. This variety of elastic 
tissue occurs chiefly in the skin and mucous 
membranes, in subcutaneous and submucous 
tissue, in the lungs and true vocal cords. 

b. Thick fibers, sometimes cylindrical, some- 
times flattened, which branch, anastomose and 
form a network : these are seen most typically in 
the ligamenta subflava and also in the ligamentum 
nuchae of such animals as the ox and horse, in 
which that ligament is largely developed, figure 40. 

A certain number of connective-tissue cells 
are found in the ground substance between 
the elastic fibers which make up this variety of 
connective tissue, page 33. 

Areolar Tissue. This variety of fibrous tissue has a very wide dis- 
tribution and constitutes the subcutaneous, subserous, and submucous tis- 
sue. It is found in the mucous membranes, in the true skin, and in the outer 

FIG. 40. Elastic Fibers 
from the Ligamenta Sub- 
X 200. (Sharpey.) 


sheaths of the blood vessels. It forms sheaths for muscles, nerves, glands, 
and the internal organs, and, penetrating into their interior, supports and con- 
nects the finest parts. 

Structure. To the naked eye it appears, when stretched out, as a fleecy, 
white, and soft meshwork of fine fibrils, with here and there wider films join- 
ing in it, the whole tissue being evidently elastic. The openness of the mesh- 
work varies with the locality from which the specimen is taken. Under the 
microscope it is found to be made up of fine white fibers, which interlace in a 
most irregular manner, together with a variable number of elastic fibers. 
On the addition of acetic acid, the white fibers swell up, and become gelatin- 
ous in appearance; but as the elastic fibers resist the action of the acid, they 
may still be seen arranged in various directions, sometimes appearing to pass 
in a more or less circular or spiral manner round a small gelatinous mass of 
changed white fiber. The cells of areolar tissues are connective-tissue 



FIG. 41. FIG. 42. 

FIG. 41. Mucous Connective Tissue from the Umbilical Cord, a, Cells; b, fibrils. 

FIG. 42. Part of a Section of a Lymphatic Gland, from which the corpuscles have 
been for the most part removed, showing the Adenoid Reticulum. (Klein and Noble 

Gelatinous Tissue. Gelatinous connective tissue forms the chief 
part of the bodies of such marine animals as the jelly-fish. It is found in 
many parts of the human embryo. It may be best seen in the " Whartonian 
jelly" of the umbilical cord and in the enamel organs of developing teeth. 

Structure. It consists of cells, which in the jelly of the enamel organ 
are stellate, embedded in a soft jelly-like intercellular substance which forms 
the bulk of the tissue. 

Adenoid or Lymphoid Tissue. Distribution. This variety of tissue 
makes up the stroma of the spleen and lymphatic glands, and is found also 


in the thymus, in the tonsils, and in the follicular glands of the tongue; in 
Peyer's patches, in the solitary glands of the intestines, and in the mucous 
membranes generally. 

Structure. Adenoid or retiform tissue consists of a very delicate network 
of minute fibrils, figure 42. The network of fibrils is concealed by being 
covered with flattened connective-tissue corpuscles, which may be readily 
dissolved in caustic potash, leaving the network bare. The network con- 
sists of white fibers, the interstices of which are filled with lymph corpuscles. 
The cement substance of adenoid tissue is very fluid. 

Neuroglia. This form of connective tissue found in the nervous system 
is described on page 78. 

Development of Fibrous Tissues. In the embryo the place of the fibrous 
tissues is at first occupied by a mass of roundish cells, derived 'chiefly from 

FIG. 43. Portion of Submucous Tissue of Gravid Uterus of Sow. a, Branched cells, 
more or less spindle-shaped; b, bundles of connective tissue. (Klein.) 

the mesoderm, but also from ectoderm and from entoderm. These develop 
either into a network of branched cells or into groups of fusiform cells, 
figure 43. 

The cells are embedded in a semifluid albuminous substance derived 
probably from the cells themselves. Later this formed material is converted 
into fibrils under the influence of the cells. The process gives rise to fibers 
arranged in the one case in interlacing networks, areolar tissue, in the other 
in parallel bundles, white fibrous tissue. In the mature forms of purely 
fibrous tissue not only the remnants of the cell substance, but even the nuclei, 
may disappear. The embryonic tissue, from which elastic fibers are devel- 
oped, is composed of fusiform cells and a structureless intercellular sub- 
stance. The fusiform cells dwindle in size and eventually disappear so 
completely that in mature elastic tissue hardly a trace of them is to be found; 
meanwhile the elastic fibers steadily increase in size. 

Adipose Tissue. In almost all regions of the human body a larger 
or smaller quantity of adipose or fatty tissue is present. Adipose tissue is 
almost always found seated in areolar tissue, and forms in its meshes little 
masses of unequal size and irregular shape, to which the term lobules is com- 
monly applied. 


Structure. Adipose tissue consists essentially of cells which present 
dark, sharply denned edges when viewed with transmitted light; each con- 
sisting of a structureless and colorless membrane or bag formed of the re- 
mains of the original protoplasm of the cell, filled with fat. A nucleus 
is always present in some part or other of the cell protoplasm, but in the 
ordinary condition of the loaded cell it is not easily or always visible. This 
membrane and the nucleus can generally be brought into view by extracting 
the fat with ether and by staining the tissue. 

FIG. 44. Blood Vessels of Adipose Tissue. A, Minute flattened fat lobule, in which 
the vessels only are represented, a, The terminal artery; v, the primitive vein; b, the fat 
vesicles of one border of the lobule separately represented. X 100. B, Plan of the 
arrangement of the capillaries, c, On the exterior of the vesicles; more high y magnified. 
(Todd and Bowman.) 

The ultimate cells are held together by capillary blood vessels, figure 44; 
while the little clusters thus formed are grouped into small masses, and 
held so, in most cases, by areolar tissue. The oily matter contained in the 
cells is composed chiefly of the compounds of fatty acids with gylcerin, olein, 
stearin, and palmitin. 

Development of Adipose Tissue. Fat cells are developed from connective- 
tissue corpuscles. In the infra-orbital connective tissue there are cells ex- 
hibiting every intermediate gradation between an ordinary branched connect- 
ive-tissue corpuscle and mature fat cells. Their developmental appearance 
is as follows: a few small drops of oil make their appearance in the proto- 
plasm, and by their confluence a larger drop is produced, figure 45. This 
gradually increases in size at the expense of the original protoplasm of the 
cell, which becomes correspondingly diminished in quantity till in the mature 
cell it forms only a thin crescentic film with a nucleus closely pressed against 
the cell wall. Under certain circumstances this process may be reversed. 

A large number of blood vessels are developed in adipose tissue, which 



subdivide until each lobule of fat contains a fine meshwork of capillaries 
ensheathing each individual fat globule, figure 44. 

Adipose tissue serves as a storehouse of combustible matter which may 
be reabsorbed into the blood when occasion requires, and, being used up 
in the metabolism of the tissues, may help to preserve the heat of the body. 

FIG. 45. A Lobule of Developing 
Adipose Tissue from an Eight-months 
Fetus, a, Spherical or, from pressure, 
polyhedral cells with large central nu- 
cleus, surrounded by a finely reticulated 
substance staining uniformly with hema- 
toxylin. b, Similar cells with spaces 
from which the fat has been removed 
by oil of cloves, c, Similar cells showing 
how the nucleus with enclosing proto- 
plasm is being pressed toward periphery. 
d, Nucleus of endothelium of investing 
capillaries. (McCarthy.) 

FIG. 46. Branched Connective- 
tissue Corpuscles, Developing 
into Fat Cells. (Klein.) 

That part of the fat which is situated beneath the skin must, by its want of 
conducting power, assist in preventing undue waste of the heat of the body 
by escape from the surface. 


All kinds of cartilage are composed of cells embedded in a substance 
called the matrix. The apparent differences of structure met with in the 
various kinds of cartilage are more due to differences in the character of 
the matrix than of the cells. With the exception of the articular variety, 
cartilage is invested by a thin but tough firm fibrous membrane called the 

Cartilage exists in three different forms in the human body, viz., hyaline 
cartilage, yellow elastic cartilage, and white fibro- cartilage. 

Hyaline Cartilage. This variety of cartilage is met with largely in 
the human body where it invests the articular ends of bones, and forms the 


costal cartilages, the nasal cartilages, and those of the larynx with the ex- 
ception of the epiglottis and cornicula laryngis, the cartilages of the trachea 
and bronchi. 

FIG. 47. FIG. 48. 

FIG. 47. Hyaline Articular Cartilage (Human). The cell bodies entirely fill the spaces 
in the matrix. X 340 diams. (Schafer.) 

FIG. 48. Fresh Cartilage from the Triton. (A. Rollett.) 

Structure. Like other cartilages, it is composed of cells embedded in a 
matrix. The cells are irregular in shape, generally grouped together in 
patches, figure 47. The patches are of various shapes and sizes and placed 

FIG. 49. Costal Cartilage from an Adult Dog, showing the Fat Globules in the Cartilage 

Cells. (Cadiat.) 

at unequal distances apart. They generally appear flattened near the free 
surface of the mass of cartilage, and more or less perpendicular to the surface 
in the more deeply seated portions. 


The intercellular substance of hyaline cartilage, when viewed fresh or 
after ordinary fixation, appears homogeneous. However, when subjected 
to special methods, the seemingly homogeneous intercellular substance can 
be shown to be made up of fibers, comparable with those found in white 
fibrous tissue, embedded in the homogeneous matrix. 

In the hyaline cartilage of the ribs the cells are mostly larger than in 
the articular variety, and there is a tendency to the development of fibers 

ttliiil. 1 ' 1 

FIG. 50. Yellow Elastic Cartilage of the 
Ear. Highly magnified. (Hertwig.) 

FIG. 51. White Fibro-cartilage. 

in the matrix, figure 49. The costal cartilages also frequently become 
calcified in old age, as also do some of those of the larynx. 

In the fetus cartilage is the material of which the bones are first con- 
structed; the "model" of each bone being laid down, so to speak, in this 
substance. In such cases the cartilage is termed temporary. It closely 
resembles the ordinary hyaline cartilage, but the cells are more uniformly 
distributed throughout the matrix. 

Elastic and White Fibro-cartilage. The first variety is found in 
the cartilage of the external ear; the latter in portions of the joints, the inter- 
vertebral cartilages, etc. 

Structure. Elastic and white nbro-cartilage are composed of cells and a 
matrix; the latter being made up almost entirely of fibers closely resembling 
those of fibrous connective tissue. 

Development of Cartilage. Cartilage is developed out of mesoblast cells 
with a very small quantity of intercellular substance. The cells multiply by 
fission within the cell capsules. 



The characteristic of bone is that the matrix is solidified by a deposit of 
earthy salts, chiefly calcium phosphate, but some magnesium phosphate and 
calcium carbonate. 

To the naked eye there appear two plans of structure in different bones, 
and in different parts of the same bone, namely, the dense or compact, and 
the spongy or cancellous tissue. In a longitudinal section of a long bone, 
as the humerus, the articular extremities are found capped on their surface 
by a thin shell of compact bone, while their interior is made up of the spongy 
or cancellous tissue. The shaft is formed almost entirely of a thick layer 
of the compact bone which surrounds a central canal, the medullary cavity, 
so called from its containing the medulla, or marrow. In the flat bones, the 
parietal bone or the scapula, a layer of cancellous structure lies between 
two layers of the compact tissue. In the short and irregular bones, as those 
of the carpus and tarsus, the cancellous tissue alone fills the interior, while 
a thin shell of compact bone forms the outside. 

FIG. 52. Cells of the Red Marrow of the Guinea-pig, highly magnified, a, A large 
cell, the nucleus of which appears to be partly divided into three by constrictions; b, a cell, 
the nucleus of which shows an appearance of being constricted into a number of smaller 
nuclei; c, a so-called giant cell, or myeloplaxe, with many nuclei; d, a smaller myeloplaxe, 
with three nuclei; e-i, proper cells of the marrow. (Schafer.) 

The Marrow. There are two distinct varieties of marrow the red and 
the yellow. 

Red marrow is that variety which occupies the spaces in the cancellous 
tissue; it is highly vascular, and thus maintains the nutrition of the spongy 
bone, the interstices of which it fills. It contains a few fat cells and a large 
number of marrow cells, many of which are undistinguishable from 
lymphoid corpuscles, and has for a basis a small amount of fibrous tissue. 
Among the cells are some nucleated cells containing hemoglobin like the 
blood corpuscles. There are also a few large cells with many nuclei, termed 
giant cells or myeloplaxes, which are probably derived from the ordinary 
marrow cells, figure 52. 



Yellow marrow fills the medullary cavity of long bones, and consists 
chiefly of fat cells with numerous blood vessels. Many of its cells are in 
every respect similar to lymphoid corpuscles. 

From these marrow cells, especially those of the red marrow, the red 
blood corpuscles are derived. 

The Periosteum and Nutrient Blood Vessels. The surfaces of 
bones, except the part covered with articular cartilage, are clothed by a 

FIG. 53. Transverse Section of Compact Bone (of humerus). Three of the Haver- 
sian canals are seen, with their concentric rings; also the lacunae, with the canaliculi extending 
from them across the direction of the lamella. The Haversian apertures were filled with 
debris in grinding down the section, and therefore appear black in the figure, which 
represents the object as viewed with transmitted light. The Haversian systems are so 
closely packed in this section, that scarcely any -interstitial lamellce are visible. X 150. 

tough, fibrous membrane, the periosteum, which is closely attached to the 
surface of the bone. Blood vessels are distributed in this membrane, and 
minute branches from these periosteal vessels enter the Haversian canals 
to supply blood to the solid part of the bone. The long bones are supplied 
also by a proper nutrient artery which, entering at some part of the shaft 
so as to reach the medullary canal, breaks up into branches for the supply 
of the marrow, from which again small vessels are distributed to the interior 
of the bone. Other small nutrient vessels pierce the articular extremities 
for the supply of the cancellous tissue. 


Microscopic Structure of Bone. Notwithstanding the differences 
of arrangement just mentioned, the structure of all compact bone substance 
is found under the microscope to be essentially the same. 

Examined with a rather high power its substance is found to contain a 
multitude of small irregular spaces, approximately fusiform in shape, called 
lacuna, with very minute canals or canaliculi, as they are termed, leading 

FIG. 54. Longitudinal Section from the Human Ulna, Showing Haversian Canals, 
Lacunae, and Canaliculi. (Rollett.) 

from them, and anastomosing with similar prolongations from other lacunae, 
figure 53. In very thin layers of bone, no other canals than these may be vis- 
ible; but on making a transverse section of the compact tissue of a long bone, 
as the humerus or ulna, the arrangement shown in figure 53 can be seen. 
The bone seems mapped out into small circular districts, at or about the 
center of each of which is a hole, around which are concentric layers, the 
lamella, the lacuna and canaliculi following the same concentric distribution 
around the center, with which indeed they communicate. 

On making a longitudinal section, the central holes are shown to be 
simply the cut extremities of small canals which run lengthwise through 
the bone, anastomosing with each other by lateral branches, figure 54, and 
are called Haversian Canals, after the name of the physician, Clopton Havers, 
who first accurately described them. 

The Haversian Canals. The average diameter of the Haversian canals 
is 50^. They contain blood vessels, and by means of them blood is con- 
veyed to even the densest parts of the bone; the minute canaliculi and lacunae 


absorbing nutrient matter from the Haversian blood vessels and conveying 
it still more intimately to the very substance of the bone which they traverse. 
The blood vessels enter the Haversian canals both from without from the 
periosteum, and from within from the medullary cavity or from the can- 
cellous tissue. The arteries and veins usually occupy separate canals. 

The lacuncc are occupied by branched cells, the bone cells or bone corpus- 
cles, figure 55, which very closely resemble the ordinary branched connective- 
tissue corpuscles. The processes of the bone cells extend into the canaliculi. 
Each cell controls the nutrition of the bone immediately surrounding it. 
Each lacunar corpuscle communicates with the others in its surrounding 

FIG. 55. Bone Corpuscles with their Processes as seen in a Thin Section of Human Bone. 


district, and with the blood vessels of the Haversian canals by means of the 
ramifications just described. 

It will be seen from the above description that bone bears a very close 
structural resemblance to what may be termed typical connective tissue. 
The bone corpuscles with their processes occupying the lacunae and canalic- 
uli correspond exactly to the cornea corpuscles lying in the branched spaces. 

The Lamella of Compact Bone. In the shaft of a long bone three distinct 
sets of lamellae can be clearly recognized: General or fundamental lamellae, 
which are just beneath the periosteum and parallel with it, and around the 
medullary cavity; Special or Haversian lamellae, which are concentrically 
arranged around the Haversian canals to the number of six to eighteen 
around each; Interstitial lamellae, which connect the systems of Haversian 
lamellae, filling the spaces between them, and consequently attaining their 
greatest development where the Haversian systems are few. 

The ultimate structure of the lamellae appears to be fibrous. A thin 
film peeled off the surface of a bone, from which the earthy matter has been 
removed by acid, is composed of a finely reticular structure, formed ap- 


parently of very slender fibers decussating obliquely, but coalescing at the 
points of intersection, as if here the fibers were fused rather than woven 
together. The reticular lamellae are perforated by the perforating fibers of 
Sharpey, which bolt the neighboring lamellae together, and may be drawn 
out when the latter are torn asunder, figure 56. These perforating fibers 
originate from ingrowing processes of the periosteum, and in the adult still 
retain their connection with it. 

FIG. 56. Lamellae Torn off from a Decalcified Human Parietal Bone at some Depth 
from the Surface, a, a, Lamellae, showing reticular fibers; b, b, darker part, where several 
lamellae are superposed; c, perforating fibers. Apertures through which perforating fibers 
had passed, are seen especially in the lower part, a, a. of the figure. (Allen Thomson.) 

Development of Bone. From the point of view of their development 
all bones may be subdivided into two classes: 

Those which are ossified directly in membrane or fibrous tissue, e.g., the 
bones forming the vault of the skull, parietal, frontal, and a certain portion 
of the occipital bones. 

Those whose form, previous to ossification, is laid down in hyaline carti- 
lage, e.g., humerus, femur, etc. 

The process of development, pure and simple, may be best studied in 
bones which are not preceded by cartilage, i.e., membrane-formed. Without 
a knowledge of ossification in membrane it is difficult to understand the much 
more complex series of changes through which such a structure as the carti- 
laginous femur of the fetus passes in its transformation into the bony femur 
of the adult (ossification in cartilage}. 

Ossification in Membrane. The membrane, afterward forming the 
periosteum, from which such a bone as the parietal is developed, consists 
of two layers, an external fibrous and an internal cellular or osteogenetic. 


The external layer consists of ordinary connective tissue, with branched 
corpuscles here and there between the bundles of fibers. The internal layer 
consists of a network of fine fibrils with nucleated cells and ground or cement 
substance between the fibrous bundles. It is more richly supplied with 
capillaries than the outer layer. The relatively large number of its cellular 
elements, together with the abundance of blood vessels, clearly mark it as 
the portion of the periosteum which is immediately concerned in the for- 
mation of bone. 

In such a bone as the parietal there is first an increase in vascularity, 
followed by the deposition of bony matter in radiating spicula, starting 
from a center of ossification. These primary bony spicula are osteo genetic 
fibers, composed of osteogen, in which calcareous granules are deposited. 
Calcareous granules are deposited also in the interfibrillar matrix. By 
the junction of the osteogenetic fibers and their resulting bony spicula a 
meshwork of bone is formed. The osteoblasts, being in part retained within 
the bone trabeciilae thus produced, form bone corpuscles. Lime salts are 
deposited in the circumferential part of each osteoblast, and thus a ring 
of osteoblasts gives rise to a ring of bone with the remaining uncalcified 
portions of the osteoblasts embedded in it as bone corpuscles. At the same 
time the plate increases at the periphery by the extension of the bony spicula 
and by deposits taking place from the osteogenetic layer of the periosteum. 
The bulk of the primitive spongy bone is gradually converted into compact 
bony tissue of the Haversian systems. 

Ossification in Cartilage. Under this heading, taking the femur as 
a typical example, we may consider the process by which the solid cartilag- 
inous rod which represents the bone in the fetus is converted into the hollow 
cylinder of compact bone with expanded ends formed of cancellous tissue 
in the adult long bone. 

The fetal cartilage is sheathed in a membrane termed the perichondrium, 
which resembles the periosteum described above. Thus, the differences 
between the fetal perichondrium and the periosteum of the adult are such 
as usually exists between the embryonic and mature forms of connective 

There are several steps in the transformation of the fetal cartilage to the 
adult bone, due to the fact that there is first an impregnation of the cartilage 
with lime salts, followed later by the resorption of this entire material with 
formation of the embryonic spongy bone, which is still later replaced by the 
permanent bone. The complicated phenomenon takes place in steps or 
sagest as follows: 

Stage of Proliferation and Calcification. The cartilage cells in and near 
the center of ossification become enlarged, proliferate, and arrange them- 
selves in rows in the long axis of the fetal cartilage, figure 57. Lime salts are 
next deposited in fine granules in the hyaline matrix of the cartilage, and this 

4 8 


gradually becomes transformed into calcified trabeculse, figure 57. The en- 
larging cartilage cells become more transparent, and finally disintegrate, the 
spaces occupied by them forming the primordial marrow cavities. During 
this stage the perichondrium has become the periosteum, and is beginning 
to deposit bone on the outside of the cartilage. 

FIG. 57. Developing Bone of Femur of the Rabbit. X 350. a, Cartilage cells; 
b, cartilage cells enlarged in the region of calcifying matrix; c, d, trabecuhc of calcifying 
cartilage covered with e, osteoblasts; /, osteocla'sts eroding the trabecuke; g, h, disap- 
pearing cartilage cells. The osteoblasts are seen to be depositing layers of bony sub- 
stance. Loops of blood vessels extend to the limit of the region in which the bone is 
forming. (Schafer, from Klein.) 

Stage of Vascular ization of the Cartilage. Processes from the osteo- 
genetic layer of the periosteum containing blood vessels break through the 
bone into the primordial marrow cavities and form the primary marrow, 
beginning at the centers of ossification, and spreading chiefly up and down 
the shaft. 

Stage of Substitution of Embryonic Spongy Bone for Calcified Cartilage. 
The cells of the primary marrow arrange themselves as a continuous epi- 



thelium-like layer on the calcined trabeculae and deposit a layer of bone, 
and ensheath them. The encased trabeculae are gradually absorbed by 
the osteodasts of Kolliker. 

These stages are precisely similar to what goes on in the growing shaft 
of a bone which is increasing in length by the advance of the process of ossifi- 

FiG. 58. Transverse Section through the Tibia of a Fetal Kitten, semidiagrammatic. 
X 60. P, Periosteum. O, Osteogenetic layer of the periosteum, showing the osteoblasts 
arranged side by side, represented as pear-s'haped black dots on the surface of the newly 
formed bone. B, The periosteal bone deposited in successive layers beneath the peri- 
osteum and ensheathing E, the spongy endochondral bone; represented as more deeply 
shaded. Within the trabeculae of endochondral spongy bone are seen the remains of the 
calcined cartilage trabeculae represented as dark wavy lines. C, The medulla, with V, V, 
veins. In the lower half of the figure the endochondral spongy bone has been completely 
absorbed. (Klein and Noble Smith.) 

cation into the intermediary cartilage between the diaphysis and epiphysis. 
In this case the cartilage cells become flattened and, multiplying by division, 
are grouped into regular columns at right angles to the plane of calcification 
while the process of calcification extends into the hyaline matrix between 




The embryonic spongy bone, formed as above described, is simply a tem- 
porary tissue occupying the place of the fetal rod of cartilage; the preceding 
stages show the successive changes at the center of the shaft. Periosteal 
bone is at the same time deposited in successive layers beneath the perios- 
teum at the circumference of the shaft, exactly as described in the section 
on ossification in membrane, and thus a casing of periosteal bone is formed 
around the embryonic endochondral spongy bone. The embryonic spongy 
bone is absorbed, through the agency of the osteoclasts, until the trabeculas 
are replaced by one great cavity, the medullary cavity of the shaft. 

FIG. 59. Transverse Section of Femur of a Human Embryo about Eleven Weeks Old. 
a, Rudimentary Haversian canal in cross-section; 6, in. longitudinal section; c, osteoblasts; 
d, newly formed osseous substance of a lighter color; e, that of greater age;/, lacunae with 
their cells; g, a cell still united to an osteoblast. (Frey.) 

Stage of Formation of Compact Bone. The transformation of spongy 
periosteal bone into compact bone is effected in a manner exactly similar 
to that which has been described in connection with ossification in mem- 
brane, page 46. The irregularities in the walls of the spongy periosteal 
bone are absorbed by the osteoclasts, while the osteoblasts which line them 
are developed in concentric layers, each layer in turn becoming ossified 
till the comparatively large space in the center is reduced to a well-formed 
Haversian canal, figure 59. When once formed, bony tissue grows to some 
extent inter stitially, as is evidenced by the fact that the lacunas are rather 
further apart in full-formed than in young bone. 


It will be seen that the common terms ossification in cartilage and ossifi- 
cation in membrane are apt to mislead, since they seem to imply two processes 
radically distinct. The process of ossification, however, is in all cases one 
and the same, all true bony tissue being formed from membrane, perichon- 
drium or periosteum; but in the development of such a bone as the femur, 
lime salts are first of all deposited in the cartilage; this calcified cartilage, 
however, is gradually and entirely reabsorbed, replaced by bone formed 
from the periosteum. Thus calcification of the cartilaginous matrix pre- 
cedes the real formation of bone. We must, therefore, clearly distinguish 
between calcification and ossification. The former is simply the infiltration 
of an animal tissue with lime salts, while ossification is the formation of 
true bone. 

Growth of Bone. Bones increase in length by the advance of the 
process of ossification into the cartilage intermediate between the diaphysis 
and epiphysis. The increase in length indeed is due entirely to growth 
at the two ends of the shaft. Increase in thickness in the shaft of a long 
bone occurs by the deposition of successive layers beneath the periosteum. 
If a thin metal plate be inserted beneath the periosteum of a growing bone 
it will soon be covered by osseous deposit, but if it be put between the fibrous 
and osteogenetic layers it will never become enveloped in bone, for all the 
bone is formed beneath the latter. 


During the course of his life, man, in common with most other mammals, 
is provided with two sets of teeth; the first set, called the temporary or milk- 
teeth of infancy, are shed and replaced by the second or permanent set. 

Temporary Teeth. 


Molars. Canine. Incisors. 


Incisors. Canine. Molars. 

212 =IO 
212 =10 

The figures indicate in months the age at which each tooth appears: 

Lower central 

Upper incisors 

First molar and 
lower lateral 


Second molar 

6 to 9 

8 to 12 

I 2 to I 5 

1 8 to 24 

24 to 30 



Permanent Teeth. 


Incisor, Canine. P^rT' 

The age at which each permanent tooth is cut is indicated in this table in years 

First molars 


Bicuspids or 



molars or 










12 to 14 

I 2 to I 5 

17 to 2 5 

Structure. A tooth is generally described as possessing a crown, neck, 
and root or roots. The crown is the portion which projects beyond the 
level of the gum. The neck is that constricted portion just below the crown 
which is embraced by the free edges of the gum, and the root includes all 
below this. 

On making longitudinal and transverse sections through its center, figure 
6 1, A, B, a tooth is found to be principally composed of a hard superficial 

FIG. 60. Normal Well-formed Jaws, from which the Alveolar Plate has been in great 
part removed, so as to expose the Developing Permanent Teeth in their Crypts in the Jaws. 

material, dentine or ivory, which is hollowed out into a central cavity which 
resembles in general shape the outline of the tooth, and is called the pulp 

The tooth pulp is composed of fibrous connective tissue, blood vessels, 
nerves, and large numbers of cells of varying shapes. On the surface in 



close connection with the dentine there is a specialized layer of cells called 
odontoblasts, which are elongated columnar cells with a large nucleus at the 
tapering ends farthest from the dentine. The cells are all embedded in a 
mucoid gelatinous matrix. 

The blood vessels and nerves enter the pulp through a small opening 
at the apical extremity of each root. 

A layer of very hard calcareous matter, the enamel, caps the dentine of 
the crown; beneath the level of the gum is a layer of true bone, called the 
cement or crusta petrosa. The enamel and cement are very thin at the neck 
of the tooth where they come in contact, the cement overlapping the enamel. 
The enamel becomes thicker toward the crown, and the cement toward 
the lower end or apex of the root. 

FIG. 61. A. A Longitudinal Section of a Human Molar Tooth, c, Cement; d, 
dentine; e, enamel; v, pulp cavity. B. Transverse section. The letters indicate the 
same as in A (Owen). 

Dentine or Ivory. Dentine closely resembles bone in chemical com- 
position. It contains, however, rather less animal matter. 

Structure. Dentine is finely channelled by a multitude of delicate tubes, 
which by their inner ends communicate with the pulp cavity, and by their 
outer extremities come into contact with the under part of the enamel and 
cement, and sometimes even penetrate them for a greater or less distance, 
figures 63, 64. The matrix in which these tubes lie is composed of "a retic- 
ulum of fine fibers of connective tissue modified by calcification, and, 
where that process is complete, entirely hidden by the densely deposited 
lime salts" (Mummery). 

The tubules of the dentine contain fine prolongations from the tooth 
pulp, which gives the dentine a certain faint sensitiveness under ordinary 
circumstances and, without doubt, have to do also with its nutrition. They 
are probably processes of the dentine cells or odontoblasts lining the pulp 



cavity. The relation of these processes to the tubules in which they lie is 
precisely similar to that of the processes of the bone corpuscles to the canalic- 




Periosteum of 

Cement. J 

Lower jaw bone. 

FIG. 62. Premolar Tooth and Surrounding Bone of Cat. 

ali of bone. The outer portion of the dentine, underlying the cement and 
the enamel, figure 63, 6, c, contains cells like bone corpuscles. 

FIG. 63. Section of a Portion of the Dentine and Cement from the Middle of the Root 
of an Incisor Tooth, a, Dental tubuli ramifying and terminating, some of them in the 
interglobular spaces b and c, which somewhat resemble bone lacunse; d, inner layer of the 
cement with numerous closely set canaliculi; e, outer layer of cement;/, lacunae; g, canalic- 
uli. X 350. (Kolliker.) 

Enamel. The enamel, which is by far the hardest portion of a tooth, 
is composed chemically of the same elements that enter into the composition 



of dentine and bone, but the animal matter amounts only to about 2 or 3 
per cent. It contains a larger proportion of inorganic matter and is harder 
than any other tissue in the body. 

Structure. Enamel is composed of fine hexagonal fibers, figures 64, 65. 

FIG. 64. 

FIG. 64. Thin Section of the Enamel and a Part of the Dentine, a, Cuticular pellicle 
of the enamel (Nasmyth's membrane); b, enamel fibers, or columns with fissures between 
them and cross striae; c, larger cavities in the enamel, communicating with the extremities 
of some of the dentinal tubuli (d). X 350. (Kolliker.) 

FIG. 65. Section of the Upper Jaw of a Fetal Sheep. A. i, Common enamel germ 
dipping down into the mucous membrane; 2, palatine process of jaw; 3, rete Malpighi. 
(Waldeyer.) B. Section similar to A, but passing through one of the special enamel germs 
here becoming flask-shaped; c, c, epithelium of mouth;/, neck;/', body of special enamel 
germ. (Rose.) C. A later stage; c, outline of epithelium of gum; /, neck of enamel 
germ; /', enamel organ; p. papilla; s, dental sac forming;//?, the enamel, germ of perma- 
nent tooth; m, bone of jaw; v, vessels cut across. (Kolliker.) Copied from Quain's 

These are set on end vertical to the surface of the dentine, and fit into cor- 
responding depressions in the same. 

Like the dentine tubules, they are disposed in wavy and parallel curves. 


The fibers are thus marked by transverse lines. They are mostly solid, 
but some of them may contain a very minute canal. 

The enamel prisms are connected together by a trace of hyaline cement 

Development. The first step in the development of the teeth consists 
in a downward growth, figure 65, A, i, from the deeper layer of stratified 
epithelium of the mouth, which first becomes thickened in the neighborhood 
of the maxillae or jaws, now also in the course of formation. This epidermal 
papilla grows downward into a recess of the imperfectly developed tissue of 
the embryonic jaw. It forms the primary enamel organ or enamel germ, and 
its position is indicated by a slight groove in the mucous membrane of the 
jaw. The next step consists in the elongation and the inclination outward 

FIG. 66. Part of Section of Developing Tooth of a Young Rat, showing the Mode 
of Deposition of the Dentine. Highly magnified, a, Outer layer of fully formed dentine; 

b, uncalcified matrix with one or two nodules of calcareous matter near the calcined parts; 

c, odontoblasts sending processes into the dentine; d, pulp; e, fusiform or wedge-shape cells 
found between odontoblasts; /, stellate cells of pulp in fibrous connective tissue. The 
section is stained in carmine, which colors the uncalcified matrix but not the calcified part. 
(E. A. Schafer.) 

of the deeper part, figure 65, B, /', of the enamel germ, followed by an in- 
creased development at certain points corresponding to the situations of the 
future milk-teeth. The enamel germ becomes divided at its deeper portion, 
or extended by further growth, into a number of special enamel germs corre- 
sponding to each of the milk-teeth, and connected to the common germ by a 
narrow neck. Each tooth is thus placed in its own special recess in the 
embryonic jaw, figure 65, c, /'. 

As these changes proceed, tnere grows up from the underlying tissue 
into each enamel germ, figure 65, c, p, a distinct vascular papilla, dental 
papilla, and upon it the enamel germ becomes molded, and presents the 
appearance of a cap of two layers of epithelium separated by an interval, 
figure 65, c, /'. While part of the subepithelial tissue is elevated to form 
the dental papillae, the part which bounds the embryonic teeth forms the 
dental sacs, figure 65, c, s; and the rudiment of the jaw sends up processes 
forming partitions between the teeth. The papilla, which is really part of 
the dental sac, is composed of nucleated cells arranged in a meshwork. in 



the outer layer of which are the columnar cells called odontoblasts. The 
odontoblasts form the dentine, while the remainder of the papilla forms the 
pulp. The method of the formation of the dentine from the odontoblasts 
is said to be as follows: The cells form elongated processes at their outer 
surfaces which are directly converted into the tubules of dentine, figure 66, c, 
and into the contained fibrils. 

Each papilla early takes the shape of the crown of the tooth to which 
it corresponds, but as the dentine increases in thickness and papilla dimin- 
ishes until when the tooth is cut only a small amount remains as the pulp. It 
is supplied by vessels and nerves which enter at the end of the root. The 
roots are not completely formed at the time of the eruption of the teeth. 

FIG. 67. Vertical Transverse Section of the Dental Sac, Pulp, etc., of a Kitten, a, 
Dental papilla or pulp; b, the cap of dentine formed upon the summit; c, its covering of 
enamel; d, inner layer of epithelium of the enamel organ; e, gelatinous tissue;/, outer 
epithelial layer of the enamel organ; g, inner layer, and h, outer layer of dental sac. X 14. 

The enamel cap is formed by the enamel cells, by the deposit of a keratin- 
like substance, which subsequently undergoes calcification. Other layers 
are formed in the same manner meanwhile. 

The temporary or milk-teeth are speedily replaced by the growth of the 
permanent teeth. 

The development of the temporary teeth commences about the sixth 
week of intra-uterine life, after the laying down of the bony structure of 
the jaws. Their permanent successors begin to form about the sixteenth 
week of intra-uterine life. 



There are two chief kinds of muscular tissue, differing both in minute 
structure as well as in mode of action, viz., (i) the smooth or non- striated, and 
(2) the striated. 


Non-striated muscle forms the proper muscular coats of the digestive 
canal from the middle of the esophagus to the internal sphincter ani; of 
the uterus and urinary bladder; of the trachea and bronchi; of the ducts 

FIG. 68. Isolated Smooth Muscle Cells from Human Small Intestine. X 400. Rod- 
shaped nucleus surrounded by area of finely granular protoplasm; longitudinal striations 
of cytoplasm. 

of glands; of the gall-bladder; of the vesiculae seminales; of the uterus and 
Fallopian tubes; of the blood vessels and lymphatics; and of the iris and 
some other parts of the eye. This form of tissue also enters largely into the 
composition of the tunica dartos of the scrotum. Unstriped muscular tissue 

FIG. 69. Smooth Muscle from Intestine of Pig, Showing Syncytial Structure, a, 
Protoplasmic process connecting two muscle fibers; b, end-to-end union of two muscle 
fibers, showing the continuity of protoplasm and myofibrils; c, nucleus of muscle fiber; 
d, granular protoplasm at the end of muscle nucleus; e, coarse myofibril;/, fine myofibril; 
g, connective-tissue cell with connective-tissue fibrils surrounding it; h, elastic fiber. (New 
figure by Caroline McGill.) 

occurs largely also in the true skin generally, being especially abundant in the 
interspaces between the bases of the papillae, and, when it contracts, the 
papillae are made unusually prominent, giving rise to the peculiar roughness 
of the skin termed cutis anserina, or goose flesh. It also occurs in all parts 



where hairs occur, in the form of flattened roundish bundles which lie along- 
side the hair follicles and sebaceous glands. 

Structure. Unstriated muscle fibers are elongated, spindle-shaped 

FIG. 70. Transverse Section through Muscular Fibers of Human Tongue. The 
deeply stained nuclei are situated at the inside of the sarcolemma. Each muscle fiber 
shows "Cohnheim's fields," that is, the sarcous elements in transverse section separated 
by clear (apparently linear) interstitial substance. X 450. (Klein and Noble Smith.) 

mononucleated cells, 7 to S/j. in diameter by 40 to 2Oo/z in length, figures 
68 and 69. The protoplasm of each cell, the contractile substance, is 
marked by longitudinal striations representing fibrils which have been 
described as contractile. The nucleus is an oblong mass placed near the 

FIG. 71. FIG. 72. 

FIG. 71. Muscle Fiber Torn Across; the sarcolemma still connects the two parts of the 
fiber. (Todd and Bowman.) 

FIG. 72. Part of a Striped Muscle Fiber of a Water Beetle prepared with Absolute 
Alcohol. A t Sarcolemma; B, Krause's membrane. The sarcolemma shows regular 
bulgings. Above and below Krause's membrane are seen the transparent "lateral discs." 
The chief mass of a muscular compartment is occupied by the contractile disc composed 
of sarcous elements. The substance of the individual sarcous elements has collected more 
at the extremity than in the center hence this latter is more transparent. The optical 
effect is that the contractile disc appears to possess a "median disc" (Disc of Hensen). 
Several nuclei, C and D, are shown, and in them a minute network. X 300. (Klein and 
Noble Smith.) 

center of the cell. It is covered by a nuclear membrane which encloses a 
network of anastomosing fibrils. 

Development. In the pig the smooth muscle of the alimentary canal 
originates in the syncytium of the mesodermal cells which surround the 


entoderm. The cells soon begin to grow into the adult spindle-shaped form 
and the fibrils make their appearance. Even in the adult muscle the syn- 
cytial connections are retained, according to Dr. McGill. 


Striated or striped muscle constitutes the whole of the muscular apparatus 
of the skeleton, of the walls of the abdomen, the limbs, etc. the whole 
of those muscles which are under the control of the will and hence termed 
voluntary; also the muscle of the heart. 

For the sake of description, striated muscular tissue may be divided 
into two classes, (a) skeletal, which comprises the whole of the striated mus- 
cles of the body except (b) the heart. 

FIG. 73. A, Portion of a Medium-sized Human Muscle Fiber. B, Separated bundles 
of fibrillae equally magnified; a, a, larger, and b, b, smaller collections; c, still smaller; d, d, 
the smallest which could be detached, possibly representing a single series of sarcous 
elements. X 800. (Sharpey.) 

Skeletal Muscle. The muscle fibers of the skeletal muscles are usually 
grouped in small parallel bundles, fasciculi. The fasciculi extend through 
the muscle, converging to their tendinous insertions. Connective-tissue 
sheaths, endomysium, surround the fasciculi and support the blood vessels, 
while a stronger sheath, the perimysium, encases the entire muscle. 

The unit of muscular structure is the fiber. Each muscle fiber is a long 
cylinder with fusiform ends. The fibers vary in diameter from 10 to ioo/z, 
while the length may reach as much as 40 mm. Each fiber is enclosed in 



a distinct sheath, the sarcolemma. The sarcolemma is a transparent structure- 
less sheath of great resistance which surrounds each fiber, figure 71. 

The substance of the fiber enclosed 
by the sarcolemma, the contractile 
substance, contains a number of oval 
nuclei distributed along the length of 
the fiber and lying just under the 
sarcolemma or through the sarco- 
plasm. Each nucleus is accompanied 
by a small mass of granular proto- 
plasm at its poles. The main mass of 
the fiber is characterized by transverse 
light and dark bands, figure 73, from 
which the name striated muscle arises. 

Longitudinal striation is also ap- 
parent under certain modes of treat- 
ment, figure 81. The muscle fibers 
can be split longitudinally into fibrils, 
called sarcostyles, figures 73 and 74, 
each of which exhibits the character- 
istic striation of the whole fiber. 
Under certain treatment the sarco- 
styles break transversely into smaller discs by cleavage at the line of 
Krause's membrane. 

The sarcostyle is, therefore, composed of a number of smaller elements 


FIG. 74. Diagram of Segment of Muscle 
Fiber, showing Sarcostyle A, Sarcous 
element ZJ, Krause's line C, Hensen's 
line D. 


FIG. 75. 

FIG. 75. Sarcostyles from the Wing Muscles of a Wasp. A, A', Sarcostyles showing 
degrees of retraction; B, a sarcostyle extended with the sarcous elements separated into two 
parts; C, sarcostyles moderately extended (semidiagrammatic). (E. A. Schafer.) 

FIG. 76. Diagram of a Sarcomere in a Moderately Extended Condition, B. K, K, 
Krause's membranes; H, plane of Henson; S, E, poriferous sarcous element. (E. A. 

joined end to end. These are the sarcous elements of Bowman. The sar- 
cous element has a highly refractive denser middle piece surrounded by a 



less refractive more fluid material. The polarizing microscope reveals the 
fact that the middle piece which corresponds in position to the dark 
transverse band is doubly refractive, anisotropic, while the surrounding 
material, the light band, is singly refractive, isotropic. 

In transverse sectioti, figure 70, the area of the muscle substance is 
mapped out into small polygonal areas by a network of clear lines called Cohn- 
heim's areas. The lines represent the substance between the sarcostyles. 
This substance probably represents the less differentiated contractile sub- 

stance, called sarcoplasm. In figure 81 

the interfibrillar sarcoplasm is indicated 

by the longitudinal and transverse lines. 

Heart Muscle. The muscle sub- 
stance of the heart is composed of 

FIG. 77. FIG. 78. 

FIG. 77. A Section of Cardiac Muscle, Diagrammatic. (From E. A. Schafer, after 

FIG. 78. Intercellular Continuity of Muscle Fibrils in Cardiac Muscle. (From E. A. 
Schafer after Przewosky.) 

mononucleated masses of protoplasm, cardiac muscle cells, in which the 
substance of the cell presents the transversely striated appearance char- 
acteristic of the voluntary muscle just described. But the heart muscle is 
physiologically much more like an involuntary muscle. The cells are rather 
small, two to four times as long as thick, and the nucleus is usually situated 
near the middle of the cell, figure 79. There is no sarcolemma; on the other 
hand, the cells present branched and irregular outlines, but adjacent cells 
interlock in close-fitting contact. 

Certain observers have described fibrils as extending across the so-called 
cell boundary and noted that not all such boundaries enclose nuclei. These 


observations suggest that cardiac muscle belongs to the group of tissues 
possessing a syncytium. However, the section of cardiac tissue may very 
possibly cut many cells without enclosing a nucleus. The continuity of 
fibrils is an important observation from the physiological point of view; see 
Circulation chapter. 

In certain parts of the heart, the cardiac tissue is not completely differ- 
entiated and retains in the adult somewhat embryonic characters; for ex- 
ample, the bundle of His running in the septum from the auricles to the 
ventricles and the cells containing Purkinje's fibers lying immediately under 
the endocardium. 

FIG. 79. 

FIG. 80. 

FIG. 79. Muscular Fiber Cells from the Heart. (E. A. Schafer.) 

FIG. 80. From a Preparation of the Nerve Termination in the Muscular Fibers of a 

Snake, a, End-plate seen only broad-surfaced; 6, end-plate seen as narrow surface. 

(Lingard and Klein.) 

Blood and Nerve Supply. The muscles are freely supplied with blood 
vessels; the capillaries form a network with oblong meshes around the fibers. 
Nerves also are supplied freely to muscles; the striated voluntary muscles 
receiving them from the cerebro- spinal nerves, and the cardiac muscle from 
both the cerebro-spinal and the sympathetic nerves. 

In striped muscle the nerves end in motor end-plates. The nerve fibers 
are medullated; and when a branch passes to a muscle fiber, its primitive 
sheath becomes continuous with the sarcolemma, and the axis-cylinder 
forms a network of its fibrils on the surface of the muscle fiber. This net- 
work lies embedded in a flattened granular mass containing nuclei of several 
kinds; this is the motor end-plate, figures 80 and 81. There is considerable 
variation in the exact form of the nerve end-plate in the muscle. In batrachia 
the nerve fiber ends in a brush of branching nerve fibrils which are accom- 
panied here and there by attached oval nuclei. 


Development. The striated muscle of the voluntary variety is usually 
developed from the mesoderm. The embryonic cells increase enormously 
in size, the nuclei multiply by fission and distribute themselves beneath the 

FIG. 81. 

FIG. 82. 

FIG. 81. Two Striped Muscle Fibers of the Hyoglossus of Frog, a, Nerve end-plate; 
by nerve fibers leaving the end-plate; c, nerve-fibers terminating after dividing into branches; 
d, a nucleus in which two nerve fibers anastomose. X 600. (Arndt.) 

FIG. 82. Developing Striated Muscular Fibers, Showing Different Stages of Develop- 
ment and Different Positions of the Unstriated Protoplasm. A. Elongated cell with 
two nuclei; the longitudinal striation is beginning to show on the right side. From a fetal 
sheep. (Wilson Fox.) B. Developing muscular fiber, showing both longitudinal 
and transverse striations at the periphery, and a central unstriated cylinder of protoplasm 
containing several nuclei. From a human fetus near the third month. (Ranvier.) n, 
Nucleus (there is usually a mass of glycogen near each nucleus); p, central unstriated 
protoplasm; s, peripheral striated substance. C. Developing muscular fiber, showing a 
lateral position of the unstriated protoplasm. From a three months' human fetus. 
(Ranvier.) n, Nucleus; g, unstriated protoplasm at one side of the fiber; s, striated sarcous 
substance with longitudinal and transverse striations. 

sarcolemma. There is a differentiation of the cell protoplasm which takes 
place by the formation of sarcostyles. This begins nearest the surface of 
the cells and proceeds toward the center of the mass. 


The sarcolemma is apparently produced from embryonic connective 

The cardiac muscle cells are at first spindle-shaped embryonic cells 
which elongate more and more. In further differentiation their protoplasm 
exhibits faint striations which pervade the cell as it grows in the great increase 
in size. The rhythmic contractions begin long before the striations appear. 


Nervous tissue has usually been described as being composed of two 
distinct substances, nerve fibers and nerve cells. The modern view of the 
nature of nerve tissue is, however, that the nerve cell and the nerve fibers 
are to be considered together as one unit, called the neurone. The neurone 


FIG. 83. Diagram Showing the Arrangement of the Neurones or Nerve Units in the 
Architecture of the Nervous System. (Raymon y Cajal.) A, Pyramidal neurone of 
cerebral cortex; B, anterior horn motor cell of spinal cord; D, collateral branches of A; E, 
medullary neurone with ascending axone; F, spinal-ganglion neurones; G, sensory axones 
of F; 7, collaterals of F in the cord. 

is embedded in, and supported by, a substance called neuroglia. This neurone 
consists of a cell body, a number of branching processes termed dendrites, 
and a long process running out from it, the neuraxone, or axone, which be- 
comes eventually a nerve fiber. The nerve cell and the nerve fiber are parts 
of the same anatomical unit, and the nervous centers are made up of those 
units, arranged in different ways throughout the nervous system, figure 83. 





While the nerve fiber is really to be considered 
as a process of the nerve cell, it is convenient to de- 
scribe it separately. Nerve fibers are of two kinds, 
medullated or white fibers, and non-medullated or 
gray fibers. 

Medullated Fibers. Each medullated nerve 
fiber is made up of the following parts: An ex- 
ternal sheath, called the primitive sheath, neuri- 
lemma, or nucleated sheath of Schwann; an inter- 
mediate, known as the medullary or myelin sheath, 
or white substance of Schwann; and a central 
thread, the axis- cylinder, or axial fiber. 

The Primitive Sheath. This is a pellucid mem- 
brane forming the outer investment of the nerve 
fiber. The sheath is constricted at intervals of a 
millimeter or less, the nodes of Ranvier. Each in- 
ternodal segment bears a single nucleus surrounded by a variable amount 
of protoplasm. This membrane is described as having its origin in the 

FIG. 84. Two Nerve 
Fibers of the Sciatic 
Nerve. A, Node of Ran- 
vier; B, axis-cylinder; 
C, sheath of Schwann 
with nuclei. X 300. 
(Klein and Noble 

FIG. 85. A Node of Ranvier in a Medullated Nerve Fiber, viewed from above. The 
medullary sheath is interrupted and the primitive sheath thickened. Copied from Axel 
Key and Retzius. X 750. (Klein and Noble Smith.) 

FIG. 86. Gray, Pale, or Gelatinous Nerve Fibers. A, From a branch of the olfactory 
nerve of the sheep; two dark-bordered or white fibers from the fifth pair are associated 
with the pale olfactory fibers, B, from the sympathetic nerve. X 450. (Max Schultze.) 

mesoblastic cells, and the nuclei are the indications of the cellular nature 
of each nodal segment. 

The Medullary or Myelin Sheath. This is the part to which the peculiar 


opaque white aspect of medullated nerves is due. The thickness of this 
layer of nerve fiber varies considerably. It is a semifluid, fatty substance 
of high refractive power. It possesses a fine reticulum (Stilling, Klein), in 
the meshes of which is embedded the fatty material. It stains well with 
osmic acid. 

The Axis-cylinder. The central thread of a medullated nerve fiber is 
the axis-cylinder. It is the prolongation of a nerve cell and extends un- 
interrupted for the full length of the fiber. It consists of a large number of 
primitive fibrillcz, as shown in the cornea, where the axis-cylinders of nerves 
break up into minute fibrils which form terminal networks. From various 
considerations, such as its invariable presence and unbroken continuity in 
all nerves, there can be no doubt that the axis-cylinder is the essential con- 

FIG. 87. Transverse Section of a Portion of the Sciatic Nerve of the Rabbit, Hardened 
in Chromic Acid and Stained with Picro-carmine, to show medullated fibers in end view. 
X 275. a, Perifascicular connective tissue; b, lamellar sheath; e, axis-cylinder. 

ducting part of the fiber, the other parts having the subsidiary function of 
support and possibly of insulation. 

The size of the nerve fibers varies, figure 87. The largest fibers are 
found within the trunks and branches of the spinal nerves, in which the 
majority measure from 14/4 to igp in diameter. In the so-called visceral 
or autonomic nerves of the brain and spinal cord medullated nerves are 
found, the diameter of which varies from i . S/i to 3 . 6/1. In the hypoglossal 
nerve they are intermediate in size, and generally measure 7 . 2fj. to 10. 8//. 

Non-medullated Fibers. The fibers of the second kind, figure 86, 
which are also called fibers of Remak, constitute the principal part of the 
trunk and branches of the sympathetic nerves, the whole of the olfactory 



nerve, and are mingled in various proportions in the cerebro-spinal nerves. 
They differ from the preceding chiefly in not possessing the outer layer of 
medullary substance; their contents being composed exclusively of the axis- 

FIG. 88. Transverse Section of the Sciatic Nerve of a Cat, about X 100. It consists 
of bundles (funiculi) of nerve fibers ensheathed in a fibrous supporting capsule, epineurium, 
A; each bundle has a special sheath (not sufficiently marked out from the epineurium in 
the figure) or perineurium, B, the nerve fibers, Nf; L, lymph spaces; Ar, artery; V, vein; 
F, fat. Somewhat diagrammatic. (V. D. Harris.) 

The non-medullated nerves are only about one-third to one-half as 
large as the medullated nerves, they do not exhibit the double contour, and 

FIG. 89. Small Branch of a Motor Nerve of the Frog, near its Termination, Showing 
Divisions of the Fibers: a, into two; b, into three. X 350. (Kolliker.) 


they are grayer than the medullated nerves. The non-medullated fibers 
frequently branch. 

It is worthy of note that in the fetus, at an early period of development, 
all nerve fibers are non-medullated. 

Nerve Trunks. Each nerve trunk is composed of a variable number 
of different-sized bundles, funiculi, of nerve fibers which have a special 
sheath, perineurium. The funiculi are enclosed in a firm fibrous sheath, 
epineurium; this sheath also sends in processes of connective tissue which 
connect the bundles together. In the funiculi between the fibers is a delicate 
supporting tissue, the endoneurium. There are numerous lymph spaces 
both beneath the connective tissue investing individual nerve fibers and 
also beneath that which surrounds the funiculi. 

FIG. 90. Terminal Ramifications of a Collateral Branch Belonging to a Fiber of the 
Posterior Column in the Lumbar Cord of an Embryo Calf. 

Bundles of fibers run together in the nerve trunk, but they merely lie 
in approximation to each other, they do not unite. Even when nerves anas- 
tomose, there is no union of fibers, but only an interchange of fibers between 
the anastomosing bundles. Although each nerve fiber is thus single through 
most of its course, yet, as it approaches the region in which it terminates, it 
may break up into several subdivisions before its final ending. 

Nerve Collaterals. It has been discovered through the researches of 
Golgi, and confirmed by the further studies of Cajal and other anatomists, 


that each individual nerve fiber in the central nervous system gives off in its 
course branches which pass out from it at right angles for a short distance, 
and then may run in various directions. These branches are called collaterals. 
They end in fine, brush-like terminations known as end-brushes, or in little 

FIG. 91. 

FIG. 92. 

FIG. 91. Nerve Cell with Short Axis-cylinder from the Posterior Horn of the Lumbar 
Cord of a o . 55 cm. Embryo Calf. (After Van Gehuchten.) 

FIG. 92. Scheme of Lower Motor Neurone. The cell body, protoplasmic processes, 
axone, collaterals, and terminal arborizations in muscle are all seen to be parts of a single 
cell and together constitute the neurone, c, Cytoplasm of cell body containing chromo- 
philic bodies, neurofibrils, and perinbrillar substance; ', nucleus; n, nucleolus; d, dendrites; 
ah, axone hill free from chromophilic bodies; ax, axone; sf, side fibril (collateral); m, medul- 
lary sheath; nR, node of Ranvier where side branch is given off; si, neurilemmaand incisures 
of Schmidt; m, striated muscle fiber; tel, motor end-plate. (Barker.) 

bulbous swellings which come in close contact with other nerve cells, 
figures 83 and 90. 

In the nerve centers, that is, in the brain and spinal cord, the different 
nerve fibers end just as the collaterals do, by splitting up into fine branches 
which form the end-brushes. Collaterals of the nerve fibers and end-brushes 


are chiefly found in the nervous centers. The nerve fibers of the peripheral 
nerves end in the muscles, glands, or special sensory organs, such as the 
eye and ear, each by its own special type of ending. Here, however, some 

FIG. 93. Large Nerve Cells with Processes, from the Ventral Cornua of the Cord of 
Man. X 350. On the cell at the right two short processes of the cell body are present, 
one or the other of which may have been an axis-cylinder process (Deiters). A similar 
process appears also on the cell at the left. 

FIG. 94. Multipolar Nerve Cell of the Cord of an Embryo Calf. 

analogy to the end-brush can also be discovered. As the peripheral nerve 
fibers approach their terminations, they lose their medullary sheath, and 
consist then merely of an axis-cylinder and primitive sheath. They may 
even lose the latter, and only the axis-cylinder be left. Finally, the axis- 


cylinder breaks up into its elementary fibrillae, to end in various ways to 
be described later. 


The nerve-cell body is the nodal and important part of the neurone, and 
from it are given off the dendrites and axis-cylinder process or axone. It 
consists of a mass of protoplasm, of varying shape and size, containing within 
it a nucleus and nucleolus. All nerve cells give off one or more processes 
which branch out in various directions, dividing and subdividing like the 
branches of a tree, but never anastomosing with each other or with other cells. 

FIG. 95. Ganglion Cells, Showing Neurofibrils. A, Anterior-horn cells of human; B, cell 
from the facial nucleus of rabbit; C, dendrite of anterior horn cell of human. (Bethe.) 

These branches are what have already been referred to as the dendrites of 
the cell. They were formerly called the protoplasmic processes, figures 91, 
93. It is thus seen that the neurone or nerve unit consists of a number of 
subdivisions, namely, the cell body, with its nucleus and nucleolus, the 
dendrites or protoplasm processes, and the axone or axis-cylinder process. 

The protoplasm of the cells is shown by various dyes to consist of neuro- 
fibrils, periftbrillar substance, and in most cells chromophilic bodies. Apathy 
and others have demonstrated that a network of interlacing and anasto- 
mosing fibrils traverses both the cell body and its branches, figure 95. 

The perifibrillar substance is a fluid or semifluid substance in which the 
fibrils are embedded. By treating nerve cells with special stains granular 
bodies varying in size are found embedded in the cytoplasm. These bodies 
are the chromophilic bodies, figure 96. 



Ganglion cells are generally enclosed in a transparent membranous 
capsule similar in appearance to the external nucleated sheath of nerve 
fibers; within this capsule is a layer of small flattened cells. 

FIG. 96. Cell of the Anterior Horn of the Human Spinal Cord, Stained by NissPs Method, 
showing chromophiles in blue, and pigment in black. (After Edinger.) 


FIG. 97. An Isolated Sympathetic Ganglion Cell of Man, Showing Sheath with 
Nucleated Cell Lining, B. A, Ganglion cell, with nucleus and nucleolus; C, branched 
process or dendrite; D, unbranched process or axone. (Key and Retzius.) X 750. 


Nerve Terminations. 

Nerve fibers terminate peripherally in four different ways: i, by the ter- 
minal subdivisions which pass in between epithelial cells, and are known as 
interepithelial arborizations; 2, by motor-plates which lie in the muscles; 
3, by special end-organs, connected with the sense of sight, hearing, smell, 
and taste; and 4, by various forms of tactile corpuscles. 

P'iG. 98. Sensory Nerve Terminations in Stratified Pavement Epithelium. Golgi's rapid 
method. (After G. Retzius.) 

The Interepithelial Arborizations. This forms a most common 
mode of termination of the sensory nerves of the body. The nerve fibers 
to the surface of the skin or mucous membrane lose their neurilemmse and 
myelin sheaths, the bare axis-cylinder divides and subdivides into minute 
ramifications among the epithelial cells of the skin and mucous membrane. 
In the various glands of the body this form of termination also prevails. 
The hair bulbs, the teeth, and the tendons of the body are supplied by this 
same process of terminal arborization, figures 98, 99. 

FIG. 99. Sensory Nerve Termination in the Epithelium of the Mucosa of the Inferior 
Vocal Cord and in the Ciliated Epithelium of the Subglottic Region of the Larynx of a 
Cat Four Weeks Old. Golgi's rapid method, n, Nerve fibers rising from the connective- 
tissue layer into the epithelial layer, where they terminate in ramified and free arborizations. 
(After G. Retzius.) 

The motor nerves to the muscles end in what are known as muscle plates, 
the details of whose structure have been already described. 

The special sensory end-organs will be described later in the chapter 
on the Special Senses. 

A fourth form of termination consists of corpuscles that are more or less 
encapsulated, and these are known as the corpuscles of Pacini, the tactile 



corpuscles cf Meissner, the tactile corpuscles of Krause, the tactile menisques, 
and the corpuscles of Golgi. 

The Pacinian Corpuscles. These nerve endings, named after their 
discoverer Pacini, are elongated oval bodies situated on some of the cerebro- 
spinal and sympathetic nerves. They occur on the cutaneous nerves 
of the hands and feet, the branches of the large sympathetic plexus about 
the abdominal aorta, the nerves of the mesentery, and have been observed 
also in the pancreas, lymphatic glands, and thyroid glands, figure 100. 
Each corpuscle is attached by a narrow pedicle to the nerve on which it is 


FIG. ioi. 

FIG. 100. Pacinian Corpuscle of the Cat's Mesentery. The stalk consists of a nerve 
fiber, n, with its thick outer sheath. The peripheral capsules of the Pacinian corpuscle are 
continuous with the outer sheath of the stalk. The intermediary part becomes much 
narrower near the entrance of the axis-cylinder into the clear central mass. A hook- 
shaped termination with the end-bulb, a, is seen in the upper part. (Ranvier.) 

FIG. ioi. Summit of a Pacinian Corpuscle of the Human Finger, showing the 
Endothelial Membranes Lining the Capsules. X 220. (Klein and Noble Smith.) 

situated, and is formed of several concentric layers of fine membrane, each 
layer being lined by endothelium, figure ioi. A single nerve fiber passes 
through its pedicle, traverses the several concentric layers, enters a central 
cavity, and terminates in a knob-like enlargement or in a bifurcation. 

The physiological import of these bodies is still obscure. 

The Tactile Corpuscles of Meissner. They are found in the papillae 
of the skin of the fingers and toes or among its epithelium. When simple 
they are small, slightly flattened transparent bodies composed of nucleated 
cells enclosed in a capsule. When compound, the capsule contains several 

7 6 


small cells. The nerve fiber penetrates the corpuscles, loses its myelin 
sheath, and divides and subdivides to form a series of arborizations. The 
terminal arborizations occupy the central part of the corpuscle, and are 

FIG. 102. Tactile Corpuscle of Meissner, Tactile Cell, and Free Nerve Ending, 
a, Corpuscle proper, outside of which is seen the connective-tissue capsule; b, fiber 
ending on tactile cell; c, fiber ending freely among the epithelial cells. (Merkel-Henle.) 

surrounded by a great number of marginal cells. The tactile corpuscles 
of Meissner serve for the special purpose of touch. 

The Corpuscles of Krause or End-bulbs. These exist in great 

FIG. 103. FIG. 104. 

FIG. 103. End-bulb of Krause. a, Medullated nerve fiber; b, capsule of corpuscle. 
FIG. 104. A Termination of a Medullated Nerve Fiber in Tendon, lower half with 
Convoluted Medullated Nerve Fiber. (Golgi.) 

numbers in the conjunctiva, the glans penis, clitoris, lips, skin, and in tendon 
of man. They resemble the corpuscles of Pacini, but have much fewer 
concentric layers to the corpuscle, and contain a relatively voluminous central 



mass composed of polyhedral cells. In man these corpuscles are spherical 
in shape, and receive many nerve fibers which wind through the corpuscles 
and end in the free extremities, figure 103. 

Tactile Menisques. In different regions of the skin of man, one meets, 
in the superficial layers and in the Malpighian layers, nerves which, after 
having lost their myelin sheath, divide and subdivide to form extremely 
beautiful arborizations. The branches of these arborizations are the tactile 
menisques. These menisques, which simulate the form of a leaf, represent a 
mode of terminal nervous arborization (Ranvier). 

The Corpuscles of Golgi. These are small terminal plaques placed 
at the union of tendons and muscles, but belonging more properly to the 

FIG. 105. Neuroglia Cells in the Cord of an Adult Frog. A, Ependyma cells 
with their peripheral extremities atrophied and ramified; B, C, D, neuroglia cells in different 
degrees of emigration and separation from the ependymal canal; their central extremity 
is atrophied and much contracted; their peripheral extremity, on the other hand, is 
greatly extended; the ramifications of the latter, terminating in conical buttons, 7, end 
under the pia mater. (After Cl. Sala.) 

tendon. They are fusiform in shape and are flattened upon the surface of 
the tendon close to its insertion into the muscular fibers. They are composed 
of a granular substance, enveloped in several concentric hyaline membranes 
which contain some nuclei. The nerve fiber passes into this little corpuscle, 
splitting itself up into fine terminals. The corpuscles of Golgi are believed 
to be related to the muscular sense, figure 104. 


The Muscle Spindles. Voluntary muscles are supplied with nerve 
terminations of a sensory nature ending in Pacinian corpuscles, in end bulbs, 
and in special structures known as neuromuscular bundles or muscle spindles. 
A muscle spindle consists of one or more muscle fibers somewhat smaller than 
the typical fibers of that particular muscle, and containing a relatively great 
amount of sarcoplasm, and many nuclei. These fibers are intimately bound 
with nerve terminations as shown in the figure 106. Certain of the vol- 
untary muscles, particularly those of the arms and legs, contain large num- 


FIG. 106. A section of a muscle spindle from a. voluntary muscle of the cat. 
A, Annular terminations; S, spiral terminations; F, arborescent terminations. (From 
Barker, after Ruffini.) 

bers of muscle spindles. In the tendons of these muscles also are numerous 
muscle-tendon organs of the Golgi type. Sherrington conclusively demon- 
strated the sensory nature of these fibers and terminations by showing that 
they did not undergo Wallerian degeneration when the corresponding anterior 
spinal nerve roots were cut and allowed to degenerate. 


The neuroglia, while not a nervous tissue, is closely mingled with it and 
forms an important constituent of the nervous system. It consists of cells 
giving off a fine network of richly branching fibers. Neuroglia is a form 
of connective tissue, and it is in its functions strictly comparable to the con- 
nective tissue which supports the special structures of other organs, like the 
lungs and kidneys. In the adult animal the neuroglia tissue is composed of 
cells from which are given off immense numbers of fine processes. These 
extend out in every direction, and intertwine among the nerve fibers and nerve 
cells, figure 105. The neuroglia cell differs in size and shape very much in 
different parts of the nervous system in accordance with the arrangement of 
the nervous structures about it. The cell is composed of granular proto- 
plasm, and lying in it is a large nucleus, within which is a nucleolus. The 
body of the cell is small in proportion to the nucleus. 


OF the eighty chemical elements which have been isolated, no less than 
seventeen combine in varying quantities to form the chemical basis of the 
animal body. The substances which contribute the largest share are the 
non- metallic elements, Nitrogen, Oxygen, Carbon, and Hydrogen oxygen 
and carbon making up altogether about 85 per cent, of the whole. The 
most abundant of the metallic elements are Calcium, Sodium, and Potassium.* 

These elements do not exist in the animal body in the free state, but are 
combined into complex chemical compounds. 

The first step in the act of separating the composition products of proto- 
plasm produces changes which destroy the chemical and physical relations 
of these products which maintain the state of life. Dead protoplasm, how- 
ever, yields a number of substances which must be very directly derived 
from the living protoplasm. On the other hand, certain products can be 
isolated from the animal body w r hich are evidently not a part of the proto- 
plasm itself, but products of protoplasmic activity. Some of these, like fat, 
glycogen, etc., are constructive products, others are disintegration products 
of protoplasmic activity. 


The nitrogenous substances in the body consist chiefly of the proteins 
or of substances which are derived from the proteins. Nitrogenous sub- 
stances occur in the solid tissues of the body and are found also to a con- 
siderable extent in the circulating fluids (the blood and lymph) and in the 
secretions and excretions. 

* The following table represents the relative proportion of the various elements in 
the body. (Marshall.) 

Oxygen 72.0 

Carbon 13 . 5 

Hydrogen 9.1 

Nitrogen 2.5 

Calcium 1.3 

Phosphorus * J 5 

Sulphur o. 1476 

Sodium o.i 

Chlorine 0.085 


Fluorine o. 08 

Potassium o . 026 

Iron o.oi 

Magnesium 0.012 

Silicon o. 0002 

(Traces of copper, lead, and alu- 




These nitrogenous substances constitute the most important and com- 
plex compounds in the body. They are essentially the organic basis of all 
living substance. At the same time they are the most important of our 
organic food stuffs. The proteins are necessary as food material for the 
continuance of life and cannot be replaced in the diet by any other organic 
or inorganic substances. Without them all life, whether animal or vegetable, 
is impossible. 

The proteins are substances containing carbon, hydrogen, and oxygen 
(which are present in fats and carbohydrates). The proteins also contain 
nitrogen and sulphur. Phosphorus and certain metallic elements are present 
as constituents of some proteins. The elementary composition of most 
protein substances falls within the following percentages: 

Carbon from 50 to 55.0 per cent. 

Hydrogen from 6 to 7 .3 per cent. 

Oxygen from 19 to 24.0 per cent. 

Nitrogen from 15 to 19.0 per cent. 

Sulphur from 0.3 to 2.5 per cent. 

Phosphorus, when present from 0.4 to 0.8 per cent. 

The individual protein substances are chemical entities. As individuals 
of a group they differ in elementary composition and in the derivatives 
which they yield on cleavage of the protein molecule. 

Chemical Structure of Proteins. Proteins are combinations of 
a-amino acids, the simplest example of which is glycocoll or a-amino acetic 
acid. Acetic acid has the formula CH 3 COOH; if the NH 2 group is sub- 
stituted for one of the H's in the CH 3 radical it is an amino acid. The 
introduction of the amino group in this way yields bodies which combine 
both with acids and with bases. It is also possible for the amino acids to 
combine with one another, with the elimination of water. The reaction, 
however, can only be brought about under certain conditions. For instance, 
glycocoll can be combined with itself as a dipeptid or combined with any 
other amino acid. The combination may be indicated by the following: 

CH 2 - NH 2 - CO I OH +H ! HN - CH 2 - COOH- 

glycocoll plus glycocoll 

CH 2 - NH 2 - CO - NH - CH 2 - COOH + H 2 O 

glycyl-glycine plus water 

A glance at the chemical formulae of the resulting dipeptid indicates 
that in this new substance there is still an amino group (NH 2 ) and a carboxyl 
group (COOH) which are not combined. Another amino acid may be 
joined on to the carboxyl root, and yet a fourth on to the remaining amino 



group, so that the still more complex peptids can be formed. When this is 
done there is yet a carboxyl and an amino group to which other amino acids 
can similarly be joined. The structure of the protein molecule accordingly 
may be represented as follows: 




- OC - C - NH - OC - C - NH - OC - C - NH - 




In which R indicates here the rest of the formula for any of the a-amino 
acids entering into the constitution of protein. 

At least eighteen amino acids have been found to enter into the composi- 
tion of the proteins. The list includes glycocoll, alanine, serine, phenyl- 
alanine, tyrosine, tryptophane, cystine, leucine, isoleucine, amino-butyric 
acid, aspartic acid, glutaminic acid, proline, oxyproline, histidine, arge- 
nine, lysine, and diaminotrihydroxydodecanoic acid. Associated with 
the amino acids there is usually a detectable amount of amino-carbohydrate. 
The chemical formulae for the more important of these are given below: 

NH 2 



H NH 2 

I I 

H H 


H NH 2 

I I 

/S I i 


I I 



(amino acetic acid.) (a-amino proprionic acid.) (Phenyl a-amino proprionic acid.) 

H NH, 

H H 


H H 


(a-amino /3-hydroxy 
proprionic acid.) 

I I 




(p-oxyphenyl a-amino 
proprionic acid.) 

| I 

H-C-NH 2 H-C-NH 2 

I I 








H NH 2 

I I 



(Indol amino proprionic acid.) 

CH 3 H NH 2 

I I I 

I I I 
CH 3 H H 

(a-amino isobutylacetic acid.) 

H NH 2 

I I 

I I I I 

CH 3 NH 2 


I I 
CH 3 H 

(a-amino isovalerianic acid.) 


NH 2 







H | 



tartic acid,. 

Glutaminic acid. 


(amino succinic acid.) (a-amino normal glutaric 


H H H NH 2 

I I I 

H -N -C -C -C -C - COOH 




(a-amino /?-imidazol proprionic acid.) 

NH 2 H H H NH 2 

(guanidine a-amino valerianic acid.) 


H H H H H 

(a-e-diamino caproic acid.) 

The amino acids belong either to what is known in organic chemistry as 
the aliphatic, carbocyclic, or heterocyclic series; that is, they are derivations 
either of the hydrocarbons, of benzene or of closed-ring compounds not 
composed wholly of carbon atoms, but in which one or more of the links 
in the closed chain are supplied by other polyvalent elements (in the proteins 
by nitrogen). Thus tyrosine and phenylalanine are carbocyclic compounds; 
histidine, proline, and tryptophane are heterocyclic compounds, and the 
remaining members of the list are aliphatic derivatives. 

Of the elements of the protein molecule, nitrogen is by far the most 


characteristic and important. The animal organism is unable to construct 
the amino acid molecules and hence cannot build up protein material from 
nitrogen of the atmosphere or from combinations, such as ammonia, nitrates, 
and nitrites. Plants, however, have the property of synthesizing proteins 
from inorganic nitrogen. The nitrogen of amino acids and protein is directly 
utilizable by the body, so that the animals are ultimately dependent upon 
plants for their protein-supply. 

Nitrogen in the protein molecule occurs in four different forms: 

1. The monamino acid nitrogen, or the nitrogen that is in the NH 2 (amino) 
group of the a position. 

2. The diamino acid nitrogen, or the basic nitrogen, as shown in the 
amino group in lysine. 

3. Amide nitrogen; the OH of the second COOH group in the dibasic 
glutaminic and aspartic acids in protein may be replaced by the amino group. 
On cleavage, the NH 2 is split off from the acid amide as ammonia. 

4. The guanidine residue as in arginine. 

The distribution of nitrogen in the protein accordingly depends on the 
amino acids entering into its composition. 

Sulphur of the protein is present in the amino acids, cystine and cystein. 

It has been stated that the amino acids are combined together in a pro- 
tein molecule, carboxyl with amino radical. On boiling the proteins with 
mineral acids, the reaction is reversed and the protein substances are split, 
with the combining of water, into the individual amino acid components. 
This change is termed a "hydroly tic cleavage." The qualitative and quan- 
titative determination of the products thus obtained have shown us that the 
proteins differ chemically both as to the individual amino acids which enter 
into the complex protein molecule and the amount of each acid present. 
Proteins, then, which may give exactly the same percentage composition and 
elementary analysis and which show practically the same physical prop- 
erties are found to be actually different individuals of the protein group 
when the products of their hydrolytic cleavage are investigated. For exam- 
ple, the following tables give the elementary composition and the amino 
acids obtained from three proteins which are present in wheat flour. 









Hydrogen . . . 




Nitrogen . . 

17 66 

I 7.4.0 



i 03 

I 08 



2 I. 7"? 



100. OO 





Percent of 





o oo 

o 89 

O Q4 


2 OO 

4 6<C 

44 ^ 

Amino valerianic acid 

O 2 I 

O 24. 

o 18 


s 61 

5O ^ 

I I 3.4 




7, l8 


2 ~l ? 

I Q7 

7 ST. 

Aspartic acid 



7.7, C 

Glutaminic acid 

2 7.7 7 


6 77. 

Serine . 

O I 7, 

O 74 



I. 2O 

4.2 < 

7,. 74 



O O2 




I O2 

2 7 e 






7. 16 

4 72 



51 j 







It has been indicated that the synthesis in very simple proteins can be 
attained by combining amino acids. A synthesis, however, can be brought 
about by the reversible action of the digestive enzymes. Recently Taylor 
has been able to synthesize a simple protein, a protamine, by the reversible 
action of a trypsin on amino acids which were previously obtained by the 
digestion of the protamine. Cleavage by enzymes is a hydrolysis of the 
same type as that mentioned above by the use of the mineral acids. In 
the concentration of the products of a digestion the enzymes act in the 
reverse manner and resynthesize these substances on which they have pre- 
viously acted. Robertson has demonstrated a similar reversible action of 
pepsin on paranuclein derived from a digestion of casein. The reversible 
action may be indicated by the equation: 


These experiments lend a new stimulus to the efforts to build up proteins 
in the chemical laboratory along the lines of catalytic action of enzymes. 
The proteins of the various tissues of the body are quite different in character 
and chemical constitution and are different from the protein of the diet. 
In digestion there is a breaking down of the protein in the food into simple 
combinations of amino acids or the acids themselves, and subsequently 
there is a selection of certain amino acids and resynthesis of characteristic 
proteins by the cells of the tissues. 


It is customary to assign to a compound having an unknown molecular 
mass, i.e., relative weight in units of the weight of an atom of hydrogen, a 
formula representing the least mass which the substance could have and 
preserve its characteristic properties. The simplest formula for oxyhemoglo- 
bin, the compound protein of the red blood cells, is C 658 H 1181 N 207 S 2 FeO 210 . 
This formula is based on the relative proportion that the C, H, N, S, 
and O bear to the Fe as determined by analysis. This protein contains 
iron, and the least Fe that one molecule can contain is one atom. By addi- 
tion of the atomic masses of the total number of atoms of each element, the 
least possible molecular mass for oxyhemoglobin is about 15,000. It might 
just as well be 30,000 with two atoms of iron in the compound. The follow- 
ing formulae have been proposed for ovalbumin and seralbumin: 

Ovalbumin, C 2 3 9 H 386 N 58 S 2 O 78 
Seralbumin, C 450 H 720 N 116 S 6 O 140 

the molecular masses being in the neighborhood of 5000 and 6000, re- 

Besides the amino acids other radicals are present in some proteins. A 
carbohydrate moiety is evidently present in certain proteins and phosphoric 
acid in others (as in the milk protein casein). Such proteins are to be dis- 
tinguished from those which exist as combinations with definite chemical 
entities, as hematin, nucleic acid, amino sugars, lecithins, etc. 

Properties of Protein. Many proteins have been prepared in crys- 
talline form, especially the reserve proteins from various seeds. Very few 
animal proteins have ever as yet been crystallized seralbumin, lactal- 
bumin, ovalbumin and hemoglobin are examples. 

The majority of the proteins are soluble in water or in dilute solutions 
of neutral salts of strong bases with alkalies. The proteins do not form 
solutions as do, for instance, the inorganic salts, but are to be regarded as a 
suspension of the molecules or molecular aggregates. Such a solution is 
known as a colloidal solution, and the proteins are frequently spoken of as 
colloids. Colloidal solutions of the heavy metals can be formed by the 
interrupted contact of metal electrodes under water. The metallic colloidal 
solutions and the protein solutions have many properties in common. 

When a true solution of a chemical substance of relatively small molecular 
weight is placed within a parchment or animal membrane, and the whole 
immersed in water, the substance in solution will diffuse through the pores 
of the membrane into the water external to it; similarly, water will pass 
through the membrane to the interior. After some time the system will 
come into equilibrium. The force which drives the dissolved substance from 
the more concentrated to the less concentrated solution is known as osmotic 
pressure. The large protein molecules and molecular aggregates cannot 
pass through the pores of the membrane, or, in other words, they are not 


diffusible. Their osmotic pressure is very slight. Some of the simpler 
derived proteins, however, are diffusible. 

Proteins in aqueous solution rotate polarized light to the left. The 
specific rotation of the individual proteins varies. The compound proteins, 
hemoglobin and nucleoproteins are dextrorotatory. 

Proteins chemically are rather unstable bodies and are easily hydrolyzed, 
through heating and standing in alcohol, into modifications which differ only 
slightly from the original substances. This change is ordinarily termed 

Proteins may be precipitated from their solutions by the addition of the 
neutral inorganic salts in high concentration or to saturation. This pre- 
cipitation is essentially a physical one, the protein remaining unchanged. 
Salting out is, then, a most valuable method for the separation and purifica- 
tion of the protein substances. The proteins form insoluble combinations 
with the so-called alkaloidal reagents; phosphotungstic acid, phospho- 
molybdic acid, picric acid, trichloracetic acid, potassium mercuric iodide, 
and tannic acid. The protein also forms insoluble albuminates with the 
salts of the heavy metals. 

The color reactions for the proteins, which are given in the laboratory 
experiments at the end of this chapter are due to a reaction between some 
one or more of the constituent radicals of the complex protein molecule and 
the chemical reagent or reagents used. Thus certain color tests are due 
to the presence of individual amino acids in the protein molecule, and the 
intensity of the reaction obtained will vary with the amount of the amino 
acids present. The negative results for a certain test will indicate the ab- 
sence of the particular amino acid in the molecular complex. The color 
tests, then, are important because they throw light on the chemical consti- 
tution of the protein under observation. 


The following classification is that adopted by the American Physio- 
logical Society and the American Society of Biological Chemists: 

I. Simple Proteins. Protein substances which yield only a-amino acids 
or other derivatives on hydrolysis. 

a. Albumins. Soluble in pure water; e.g., ovalbumin, seralbumin, and 
the vegetable albumins. 

b. Globulins. Insoluble in pure water, but soluble in neutral solutions 
of strong bases with strong acids; e.g., ovoglobulin, edestin, and other vege- 
table globulins. 

c. Glutelins. Simple proteins insoluble in neutral solvents, but readily 
soluble in very dilute acids and alkalies. These substances occur abundantly 
in the seeds of cereals. 


All of the above are coagulable by heat. 

d. Prolamins or Alcohol- soluble Proteins. Soluble in 70 to 80 per cent, 
alcohol; insoluble in water, absolute alcohol, and other neutral solvents; e.g., 
zein from corn, gliadin from wheat, and hordein from barley. 

e. Albuminoids. Simple proteins characterized by a pronounced in- 
solubility in all neutral solvents. These form the principal organic con- 
stituents of the connective tissues of animals including their external covering 
and its appendages. Examples: elastin, collagen, and keratin. 

The above sub-classes are characterized by physical rather than by 
chemical differences. When the protein, for instance, is termed a globulin 
it means that it is a typical simple protein with certain characteristic solu- 
bilities. Proteins intermediate in character between albumins and globulins 
are met with, and the use of these terms as a hard-and-fast classification 
has led to considerable confusion. 

/. Histones. On hydrolysis these yield a large number of amino acids, 
among which the basic ones predominate. The histones stand chemically 
between the typical simple proteins and the following group of protamins. 
Examples are: globin, thymus histone, scombrone. 

g. Protamines. Simpler polypeptids than the proteins included in the 
preceding groups. They yield comparatively few amino acids, among which 
the basic ones predominate. They are the simplest natural proteins. 
Examples are: salmin, sturine, clupeine, and scombrine. 

II. Conjugated Proteins. Substances which contain the protein mole- 
cule united to some other molecule or molecules otherwise than as a salt. 

a. Nucleoproteins. Compounds of one or more protein molecules with 
nucleic acid; e.g., nucleohistone. 

b. Glycoproteins. Compounds of the protein molecule with a substance 
or substances containing a carbohydrate group other than a nucleic acid; 
e.g., mucins and mucoids. 

c. Phosphoproteins. Compounds of the protein molecule with phos- 
phorous containing substances other than a nucleic acid or lecithin; e.g., 
casein, ovovitellin. 

d. Hemoglobins. Compounds of a protein molecule with hematin or 
some similar substance. These include the respiratory pigments; e.g., 
hemoglobin and hemocyanin. 

e. Lecithoproteins. Compounds of the protein molecule with the lipoid 
lecithin; e.g., lecithans, phosphatides. 

III. Derived Proteins. Class i. Primary Protein Derivatives. 
Derivatives of the protein molecule apparently formed by hydrolytic changes 
which involve only slight alteration of the protein molecule. 

/. Proteans. Insoluble products which apparently result from the in- 
cipient action of water, from dilute acids or enzymes; e.g., myosan, edestan. 
g. Metaproteins. Products of the further action of acids and alkalies 


whereby the molecule is so far altered as to form products soluble in very 
weak acids and alkalies, or insoluble in neutral solutions; e.g., acid meta- 
protein, acid albuminate, alkali metaprotein or alkali albuminate. 

h. Coagulation Proteins. Insoluble products resulting from i, the action 
of heat on protein in solution or, 2, the action of alcohol on the protein. 

Class 2. Secondary Protein Derivatives. Products of more extensive 
hydrolytic cleavage of the protein molecule than that in the preceding class. 

i. Proteoses. Soluble in water, non-coagulable by heat, and precipitated 
by saturating their solutions with ammonium or zinc sulphate. 

;. Peptones. Soluble in water, non-coagulable by heat, and not pre- 
cipitated by saturating their solutions with ammonium sulphate. 

k. Peptides. Definitely characterized combinations of two or more 
amino acids, the carboxyl group of one being united with the amino group 
of the other with the elimination of a molecule of water. 


Albumins. Albumins constitute the first class of simple proteins. 
They may be defined as simple proteins which are coagulable by heat and 
are soluble in pure (salt-free) water. As a rule, they are not precipitated on 
saturating their solutions with sodium chloride or magnesium sulphate, 
unless the solution be then acidified with dilute acid. They do not coagu- 
late out on heating their solution unless a trace of a salt is present. Some 
albumins have been prepared in crystalline form; e.g. ovalbumin, serum- 
albumin, and lactalbumin. Crystallization is obtained on adding ammonium 
sulphate to the protein solution until slight turbidity results, then clearing 
the solution by adding a little water and acidifying slightly with acetic acid. 
The albumins, as a rule, are precipitated on saturating with neutral ammo- 
nium sulphate. Zinc sulphate may be employed when it is desired not to 
introduce ammonium salts into the precipitation. The proteins are pre- 
cipitated and subsequently coagulated by the addition of an excess of alco- 
hol. They remain in solution on removal of inorganic salts by dialysis. 

On heating a solution of an albumin (or a globulin) the turbidity and 
flocking out of the coagulum occur at a temperature which is more or less 
characteristic for the individual protein. However, the coagulation tem- 
perature can be varied according to the concentration of the protein solu- 
tion, the presence of inorganic salts, and by the reaction of the solution. The 
coagulation temperatures, then, cannot be given as definite characters for 
individual proteins unless the conditions under which the figures were ob- 
tained are comparable. 

The albumins differ among themselves in the cleavage products they 
yield on hydrolysis, in their elementary composition, and in the specific 
rotation and coagulation temperatures. The serum albumin and lact- 


albumin are quite closely related chemically, though differing in their specific 
rotation of polarized light. The albumins contain, as a rule, more sulphur 
than do the other classes of proteins. 

Globulins. The globulins are simple proteins which are insoluble in 
pure (salt-free) water, but which are soluble in neutral solutions of salts of 
strong bases with strong acids. Most globulins are precipitated from 
their solutions on slight acidification and on saturation with sodium chloride 
and magnesium sulphate. They are precipitated also from other solutions 
on adding equal volume of saturated ammonium sulphate solution; this 
precipitation is commonly termed " precipitation at half saturation ammon- 
ium sulphate." Since they are insoluble in pure water, dilution of the 
weak salt solution containing protein causes precipitation. The globulins 
are especially predominant in the vegetable kingdom. They occur in rela- 
tively large amounts as the reserve protein in seeds of various sorts. There 
are, however, no essential differences as a class between the globulins of 
animal and of vegetable origin. 

The globulins are precipitated from weak salt solutions on dialysis in 
pure water. The inorganic salts diffuse through parchment, and with the 
reduction in salt content the globulins are precipitated. Many of the 
vegetable globulins can be obtained in crystalline form by precipitating 
them in this way. 

As a class the globulins are relatively less stable than the albumins. 
They are converted over into proteans on successive reprecipitation or 
simply by standing under water. 

Albuminoids. The albuminoids yield similar amino acids on hydrol- 
ysis to those obtained from the simple proteins. They possess essentially 
the same general chemical structure. They differ from all other proteins in 
that they are insoluble in neutral solvents. The classification, then, is based 
purely on this property, though they are characterized by their occurrence as 
the principal organic constituents in the structure of the supporting tissues 
of the body and of the skin and its appendages. The individual albumin- 
oids differ from each other fundamentally in certain chemical character- 
istics. The albuminoids also are differentiated along with the morphologi- 
cal variations of the connected tissues in which they occur. For example, 
the keratins occur in the skin and its appendages. Collagen is the principal 
albuminoid of white fibrous tissue, though found also in cartilage and bone. 
Elastin characterizes the yellow elastin tissue, as, for instance, the nuchal 
tendon, the elastic tendon so well developed in the neck of the ox. 

Keratins. The epidermis of the skin, the nails, hair and horn, feathers, 
tortoise shell, silk, and the supporting neuroglia of nervous tissue may be 
considered to be keratins in relatively pure form. The keratins take the 
form of the tissue from which they are prepared. On heating they are 
decomposed with the odor of burnt horn. They are insoluble in water, 


alcohol, and ether, and in the ordinary protein solvents. They are not 
acted upon by gastric or pancreatic juices. On heating to 150 to 200 C. 
in water the protein is hydrolyzed and dissolves. The keratins are also 
soluble in the caustic alkalies, especially on heating. Keratins from any 
source may be prepared in pure form by treating with artificial gastric juice, 
artificial pancreatic juice, boiling alcohol, and boiling ether, from twenty- 
four to forty-eight hours being devoted to each process. Several keratins, 
so far as their chemical structure is concerned, exist. 

Collagen. Collagen can be most satisfactorily prepared from the tendo 
achillis of the ox. It forms the principal organic constituent of this and 
other white fibrous tissues, as shown by the analysis given in the following 



Water 62 . 87 per cent. 

Solids 37 . 13 per cent. 

Inorganic matter 0.47 

Organic matter 36 . 66 

Fatty substance (ether-solu- 
ble) i . 04 

Coagulable protein 0.22 

Mucoid 1.28 

Elastin 1.63 

Collagen 31 . 59 

Extractives, etc 0.90 

The collagen from various sources in common with the keratin is not 
identical in composition. It differs from the keratin in containing less 
sulphur. It does not give the reaction for tryptophane and contains but 
little tyrosin. It is dissolved by pepsin and hydrochloric acid, but not by 
pancreatic juice. 

The general characteristic of collagen is that it is hydrolyzed into gelatin 
by boiling with water or dilute acid. Gies has shown that ammonia is 
liberated by this procedure. Gelatin is soluble in hot water, but its solutions 
form a jell when cooled. Inasmuch as tyrosin and tryptophane are not 
present in the gelatin molecule, this albuminoid is not a satisfactory substi- 
tute for the protein constituents in the normal diet. 

Elastin. Elastin is the principal solid constituent of yellow elastic 
tissue; e.g., the ligamentum nucha. It gives the ordinary protein color re- 
actions. It contains, however, a relatively small amount of sulphur. Elas- 
tin is dissolved by pepsin hydrochloric acid and by pancreatic juice, and 
unlike collagen it is not converted into gelatin on prolonged boiling with 
water or dilute acids. 




Water 57-57 P er cent. 

Solids 42.43 per cent. 

Inorganic matter 0.47 

Organic matter 41.96 

Fatty substance (ether-solu- 
ble) 1. 12 

Coagulable protein 0.62 

Mucoid 0.53 

Elastin 31.67 

Collagen 7 . 23 

Extractives, etc 0.80 

Histones. The histones are proteins which stand in their chemical 
structure between the true proteins and the protamines. On hydrolysis 
they yield a large number of amino acids, among which the basic ones pre- 
dominate. The basicity, however, is only slight. They are precipitated 
by dilute ammonia and this precipitate is soluble in an excess of ammonia 
in the absence of ammonium salts. They are precipitated by nitric acid, 
the precipitate dissolving on heating and again appearing on cooling. They 
give precipitates with solutions of other proteins. On heating, the histones 
yield a coagulum which is easily soluble in very dilute acids 

The histones are found in the nuclei of the red blood cells of birds, the 
unripe testis in salmon and mackerel and in the ripe spermatozoon of the 
sea-urchin. The thymus contains histone. The liver, kidneys, ox pan- 
creas, and testis of mammals contain no histone-like substances. The 
globin of the compound protein hemoglobin is to be regarded as a histone. 

Protamines. The protamines are basic proteins which are combined 
with nucleic acid and form the chief constituent of the spermatozoa of the 
salmon and other fish. They are relatively simple proteins yielding com- 
paratively few amino acids on hydrolysis, among which the basic ones 
predominate. From elementary analyses the following formula has been 
suggested for the platinum salt of salmine. C 30 H 57 N 17 O 6 .4HC1.2PtCl 4 . 
As seen from the formula, the protamines are extremely rich in nitrogen 
which comprises from 25 to 32 per cent, of their weight. The protamines 
dissolve in water and give a faintly alkaline reaction. They are precipitated 
in acid solution by platinic chloride. The protamines, after the addition of 
ammonia, precipitate true proteins, proteoses, and nucleic acid. On hy- 
drolysis all protamines yield relatively large amounts of argenine and varying 
amounts of histone, lysin, proline, alanine, valine, leucin, tyrosin, and ap- 
parently also tryptophane. Protamines also do not contain sulphur or a 
carbohydrate moiety. They are not changed by digestion with pepsin 
hydrochloric acid. 


Conjugated proteins consist of a protein molecule united with some 
other molecule or molecules otherwise than as a salt. There are nucleo- 
proteins, glycoproteins, phosphoproteins, hemoglobins or chromoproteins and 
lecithoproteins five classes of conjugated proteins. 

Nucleoproteins. Nucleoproteins contain phosphorus and in most 
instances iron. They are combinations of simple proteins with a substance 
known as nucleic acid. On boiling with strong acids they undergo hydroly- 
tic cleavage, yielding the ordinary protein cleavage products from the pro- 
tein in the combination, and purine and pyrimidine bases, carbohydrates 
and phosphoric acid from the nucleic acid moiety. Nucleoproteins are 
differentiated from the phosphoproteins in that the latter do not yield purine 
and pyrimidine bases on hydrolytic cleavage. Nucleoproteins are the es- 
sential organic constituents of cell nuclei. They go into solution when the 
tissues are extracted with cold water or dilute salt solution. They are pre- 
cipitated from these extracts by careful acidification and dissolved if an 
excess of acid is added. The solutions of nucleoproteins coagulate on 
heating. They give the color reactions of proteins. 

By boiling nucleoproteins with water or very dilute acetic acid, some 
of the protein is split off. There result substances which are precipitated 
by very dilute acids. These bodies are known as /^-nucleoproteins and 
have a smaller carbon and higher phosphorus content than the original nu- 
cleoprotein. On digestion of the original nucleoprotein or of the /?-nucleo- 
protein with pepsin hydrochloric acid, a precipitate of nuclein is obtained. 
On further digestion with pepsin hydrochloric acid, or with trypsin, or on 
cleavage with acids and alkalies, there is a complete splitting away of the 
protein, and substances are formed known as nucleic acids. The structure 
and cleavage of the nucleoprotein is indicated in the following diagram. 


on boiling with water or on digestion 
with pepsin hydrochloric acid yields 

Nuclein Protein 

On long boiling with water, i 
per cent, hydrochloric acid, or 
dilute alkalies gives 

Nucleic acid Protein 

Nucleic acids are not merely known as cleavage products of nucleopro- 
tein, but occur preformed in the cell nuclei. A special group of nucleic 
acids are bound with protamines to form the principal constituent of the 


Nucleic acids are white, amorphous substances containing 9 to 10 per cent, of 
phosphorus. According to Levine the composition corresponds to C43H 6 7Ni 6 P 4 Ojo. 
Nucleic acids give none of the protein reactions. In the sperm they are united with the 
strongly basic protamines and so are acid in character. They may be precipitated, 
however, by tannic acid, picric acid, or phosphotungstic acid as are other organic bases. 
Nucleic acid has been isolated from many different tissues and apparently is a 
uniform constituent of the nuclei of all cells. The nucleic acids from different animal 
tissues are apparently identical and similarly the nucleic acids of vegetable origin are 
identical, though there are marked chemical differences between these two types. 

The structure of plant nucleic acid is the better known of the two. Thanks to the 
extensive investigations of Levine, and Jones, and their co-workers, plant nucleic acid 
has been shown to be composed of four different nucleotides. These nucleotides are 
composed of a purine or pyrimidine base linked to phosphoric acid by carbohydrate 
groups. In the case of yeast or plant nucleic acid, the carbohydrate is a pentose 
(d. Ribose). The first of the nucleotides studied was guanylic acid which contains the 
purine base quanine or 2 ammo- 6 oxypurine. 

O = C NH 
O H H H H H || 

MM! /NH-C C = NH 

\N C NH 

Guanylic acid. 

The other three nucleotides contain adenine and the pyramidine bases uracil and 
cytosine respectively. The tentative structure of yeast nucleic acid is probably that of 
a tetra nucleotide, though the mode of linkage of the different groups is still in doubt. 

HO/ guanine. 


HO/ cytosine. 


O = PO.C5H 8 O3.C4H 3 N a O 2 
HO/ uracil. 


0=PO.C6H 8 O 3 C 6 H 4 N 6 
HO/ adenine. 

The structure of animal nucleic acid is less well known. It contains a hexose instead 
of a pentose group and thymine in place of uracil. 

Purines. To the purines belong a number of extremely important animal 

and plant substances, including adenine, guanine, hypoxanthine, xanthine, 

and uric acid, and the methyl purines caffeine, theobromine, and theophylline. 

The mother substance of the purines is known as purine, which has the 

following structure: 

iN-C 6 N = CH 

a C C 5 -N\ HC 6-NH 

1 / 8 \CH 

6- N 9 / / un 

N_ C -N 
Purine ring. Purine. 



Adenine and guanine may be converted into hypoxanthine and xanthine, 
respectively, when added to extracts of tissues, such as the liver and the thymus, 
spleen and pancreatic glands. The "deamidization" is brought about by 
specific enzymes or non-living ferments which have been termed adenase and 
guanase. On slight oxidation, hypoxanthine is converted into xanthine, and 
the latter into uric acid. This change can also be brought about in the body 
by oxidizing enzymes. The relation of the purine bases to uric acid is indicated 
in the following scheme: 


(6-amino purine.) 
N = C-NH 2 

+ H 2 


-NH 3 







on oxi- 




H 2 N-C C- 

+ H 2 


I I > 

-NH 3 

= C 

(2-amino 6-oxypurine.) 

on oxidation 
:-NH O 


( 2-6di-oxypurine.) 


>C = 

Uric acid. 
( 2-6-8-trioxy purine.) 

Glycoproteins. The glycoproteins are to be considered as compounds 
of protein and considerable quantities of a carbohydrate complex. The car- 
bohydrate group can be split from the protein by boiling with mineral acids or 
by the action of alkalies. The group of glycoproteins includes a number of 
proteins, of which the mucines and mucoids are the most important. 

Mucines are very widely distributed. They give the mucilaginous 
character to many secretions and are formed and discharged through the 
respiratory, digestive, and other tracts, partly by mucous cells and in part by 
the mucous glands, especially by the submaxillary and sublingual sali- 
vary glands, and in the bile passages. On hydrolysis the mucines are split, 
the carbohydrate moiety yielding glucose amine or galactose amine. 

Mucoids occur in the connecting tissues along with the albuminoids. 
They are found especially in the tendon, bone, and cartilage. They are 
combinations of protein and a carbohydrate containing ethereal sulphuric 
acid known as chondroitin sulphuric acid. On cleavage, besides the products 
formed from the protein, they yield sulphates and a reducing substance. 

Phosphoproteins. The phosphoproteins, sometimes called nucleo- 
albumins, are compounds of the protein molecule with some as yet unde- 
fined phosphorus-containing substance other than a nucleic acid or lecithin. 
While the phosphorus content of these substances is quite similar to that 


of the nucleoproteins, they do not yield any purine or pyrimidine bases on 
hydrolytic cleavage. Two of the best known phosphoproteins are the 
casein of milk, and vitellin of the egg yolk. The phosphorus is apparently 
present as a phosphoric acid ester. 

Hemoglobins. These are compounds of the simple protein histone, 
with an iron-, or in some lower animals, copper-, or manganese-containing 
pigment substance. The hemoglobins are more fully discussed in the chapter 
on the Blood. 

Lecithoproteins. These are combinations of proteins and a fat-like 
substance, lecithin. Lecithin is a compound of fatty acids, glycerin, phos- 
phoric acid, and an ammonium-like organic base, choline. The combination 
of lecithin and protein is apparently a loose one: the lecithin ordinarily can 
be split off by boiling alcohol. The lecithoproteins include substances 
commonly termed lecithans and phosphatids. 

The derived proteins are formed as intermediate products in the hydro- 
lytic cleavage of the original protein molecule. The primary protein de- 
rivatives are "apparently formed through hydrolytic changes which involve 
only slight alteration of the protein molecule." 

Metaproteins. These are formed from the simple proteins by the 
action of weak acids and alkalies. This class comprises what have com- 
monly been termed acid and alkali albuminates. The metaproteins are 
soluble in acid or alkaline solution, but are insoluble in neutral solutions. In 
the formation of alkali metaproteins, the sulphur in organic combination 
is split off. Thus the alkali metaprotein differs from the acid metaprotein 
in that the former contains little or no sulphur. It is impossible, then, to 
transform an alkali metaprotein into an acid metaprotein, though the acid 
metaprotein can be changed into the other modification. Acid metaproteins 
are the first products formed in the pepsin hydrochloric acid digestion of 

Coagulated Proteins. Unaltered typical simple proteins in solution are 
altered when heated or by long standing under alcohol. They are transformed 
into a coagulated modification no longer soluble in water or dilute salt solu- 
tions. A similar change occurs when solutions of the proteins are con- 
tinuously shaken or by the action of enzymes, as in the formation of fibrin 
from fibrinogen in the clotting of the blood. On treating coagulated proteins 
with acids or alkalies they are converted into the respective metaproteins. 

Secondary Protein Derivatives. Secondary protein derivatives are 
intermediary cleavage products which result from a more profound change 
than occurs in the formation of the primary derived protein. 

Proteases or albumoses are intermediate products in the digestion of 
proteins by proteolytic enzymes or in the cleavage with acids. Peptones 
are yet more simple products than the proteoses and are to be regarded 
as relatively simple polypeptides which still retain some of the protein 


characteristics. A number of proteoses and peptones have been described. 
However, there is no sharp dividing line between the more simple proteoses 
and more complex peptones, or between the simple peptones and the peptides. 
(The term peptide as at present understood designates only those combina- 
tions of amino acids possessing a known definite structure.) The peptones 
differ from the proteoses in being more diffusible, being non-precipitable 
on saturation with ammonium sulphate, and by their failure to give certain 
protein reactions. As a class, proteoses and peptones are relatively very 
soluble and are non-coagulable by heat. 

Melanins are the pigmentary substances found in the hair, feathers, skin, 
the choroid coat of the eye, and in some tumors. Products similar to the 
naturally occurring melanins are obtained on hydrolizing nearly all proteins 
with acids. The melanins are sulphur- containing acid-like substances, and 
seem to be combinations of amino-sugars (glucosamine) with certain amino- 
acids, especially tyrosine, tryptophane, and lysine. Iron is found in some of 
the melanins. 


Fats occur very widely distributed in the plant and animal kingdom, and 
constitute one of the four classes of food stuffs. Fats are esters or ethereal 
salts consisting of an organic radical (glycerol) united with the residue of an 
organic acid. Ethyl alcohol may be combined as an ester with acetic acid. 

CH 3 COOH + C 2 H 5 OH = CH 3 COOC 2 H 5 + H 2 O 

Acetic acid Alcohol Etyhl acetate 

Similarly the triatomic alcohol glycerol may be combined with the 
higher fatty acids to form the true fats. 

CH 2 OH CH 2 -OOCC 15 H 31 

CHOH + 3 C 15 H 31 COOH = CH- OOCC 15 H 31 + 3 H 2 O 

CH 2 OH CH 2 -OOCCi 5 H 31 

Glycerol Palmitic acid Tri-palmitin 

The animal fats are for the most part mixtures of tri-palmitin, tri- stearin, 
and tri-olein, the last two being esters of glycerol with stearic acid, C 17 H 35 
COOH, and, with the unsaturated oelic acid, C 17 H 33 COOH. Human fat 
consists of a mixture of which tri-palmitin and tri-stearin comprise three- 
fourths of the whole. The fat in milk and butter is in part tri-butyrin, the 
ester of glycerol with butyric acid, C 2 H 5 COOH. The percentage of any 
individual fat in animal tissue depends on, and is characteristic of, the particu- 
lar species of animal from which the fat was obtained. Ordinary mutton fat 
contains more tri-stearin and less tri-olein than pork fat, and the mutton 
fat is stiffer because the melting-point of the tri-stearin is the highest of 
the fats. 

The pure fats are odorless, tasteless, and generally colorless. They 


are insoluble in water and cold alcohol, but are dissolved by acetone, hot 
alcohol, benzol, chloroform, and ether. When shaken with water, protein 
solutions, soap, or gum arabic, the fats assume a finely divided condition 
known as an emulsion. The suspension in water is only temporary, while 
the emulsions are permanent. 

The fats are hydrolyzed or saponified by superheated steam into glycerol 
and the fatty acids, the reaction being the reverse of that indicated in the 
equation above. On boiling with caustic alkalies, they are similarly saponi- 
fied; the fatty acids are then combined with the bases to form salts or soaps. 

Lecithins are tri-glycerides in which the H atom of two instead of three 
groups of the glycerol is replaced by a fatty acid radical; for the H of the 
third hydroxyl (OH) group there is substituted an ester-like combination 
of phosphoric acid with a nitrogen-containing organic base, choline. 

CH 2 OOCC 17 H 


CHOOCC 17 H 35 C 2 H 4 OH 

CH 2 O - O P - O C 2 H 4 N=(CH 3 ) 3 

\ \ 

(CH 3 ) 3 =N OH 


Lecithin Choline 

On saponification the di-stearyl lecithin molecule above combines with 
three molecules of water and is split into two molecules of stearic acid, one 
of glycero-phosphoric acid and one of choline. 

The lecithins are soluble in alcohol, benzene, chloroform, and ether. 
They are precipitated from chloroform or alcohol-ether solution by 

The lecithins are found in nearly all animal and vegetable tissues, espe- 
cially in nervous tissues. They are essential constituents of the cell. 
Kephalin is of more than passing interest in that its presence hastens 
blood clotting. It accomplishes this result by removing the restraints 
of antithrombin on fibrin formation. 

Cholesterol is a complex alcohol with the elementary formula C 27 H 45 OH, 
and related to the vegetable terpenes, being grouped with the fats solely 
because of its physical properties. Accordingly, it cannot be saponified. It 
crystallizes in the form of thin, colorless, transparent plates usually notched 
in one corner. It exists in the tissues in part in the form of esters with the 
complex fatty acids. Cholesterol is an essential cell constituent; it is present 
in relatively large amounts in nervous tissue. It occurs also in wool fat, eggs, 
milk, and blood plasma. 

Cholesterol and the lecithins are often termed lipoids or fat-like 



The typical carbohydrates contain carbon combined with hydrogen and 
oxygen in the proportion to form water. Other substances, such as acetic 
acid, CH 3 COOH, lactic acid, CH 3 CHOHCOOH, and inosit, (CHOH) 6 , 
which contain hydrogen and oxygen in the proportion to form water, are not 
carbohydrates. Certain true carbohydrates also do not fulfill this condition. 
Chemically, the carbohydrates are aldehyde or ketone derivatives of complex 
alcohols; i.e., they have the structure 

R - CHOH - CHO or R - CO - CH 2 OH 

Aldose Ketose 

Accordingly, the carbohydrates are termed aldoses or ketoses. They 
are commonly classified by the number of carbon atoms in the molecule; 
e.g., pentoses are those containing five carbon atoms, and hexoses have six 
carbons. Each member of the carbohydrate class, with the exception of 
the pentoses, may be regarded as containing the saccharide group, C 6 H 10 O 5 . 
The monosaccharides are then C 6 H 10 O 5 + H 2 O; the di-saccharides contain 
two saccharide groups with water, (C 6 H 10 O 5 ) 2 +H 2 O, while the poly- 
saccharides contain this group taken a large number of times, (C 6 H 10 O 5 ) n . 
In general, the solubility of the saccharides varies inversely with the 
number of saccharide groups present: the mono-saccharides, as a class, 
being the most soluble and the poly-saccharides being the least so. On 
boiling in the autoclave or with mineral acids, and by the action of amylo- 
lytic and inverting enzymes, the poly-saccharides are, as a rule, hy- 
drolyzed into the simple carbohydrates. The reaction may be indicated 

(C 6 H 10 5 ) n + nH 2 = nC 6 H 12 6 

Poly-saccharide Water Mono-saccharide 

Simple poly-saccharides, and di-saccharides are formed as intermediate 
products in the cleavage and in turn these are further hydrolyzed. 

C 12 H 22 U + H 2 , , 2C 6 H 12 O e 

Di-saccharide Water Mono-saccharide 

The color reactions with iodine, fermentation with yeast and bacteria, 
the formation of characteristic crystalline osazones with phenylhydrazine 
and the reducing of alkaline solutions of the oxides of metals like copper, 
bismuth, mercury, and ammoniacal silver solutions, are the most widely 
used reactions for testing and differentiating the carbohydrates. The 
reduction of alkaline solutions of the metallic oxides is due to the easily 
oxidized aldehyde and ketone structure of the sugar. 


The more common carbohydrates may be listed as follows: 

1. Mono-saccharides. 

Hexoses, C 6 H 12 O 6 dextrose, levulose, galactose. 

Pentoses, C 5 H 10 O 5 arabinose, xylose, rhamnose (methylpentose, 

C 6 H 12 5 ). 

2. Di-saccharides, C 12 H 22 O n , 

Maltose, saccharose (cane-sugar), lactose. 

3. Poly-saccharides, (C 6 H 10 O 5 ) n . 

Dextrin group dextrins. 

Starch group starch, inulin, lichenin, glycogen. 

Cellulose group cellulose. 

Dextrose (glucose, grape-sugar) is an aldose found in honey and 
in many fruit juices where it is usually associated with levulose. It is 
present in the blood in small amounts, o.i to 0.15 per cent., in normal 
urine in minute traces, and in diabetic urine. It is not as sweet as cane- 
sugar. Glucose is produced on boiling starch with dilute acids. It is very 
soluble in water and is slightly soluble in alcohol. It crystallizes from 
water in leaves or plates and from alcohol in anhydrous needles. Dextrose 
rotates the plane of polarized light to the right its specific rotation is given 
by the expression [a] d = +52.5. It forms a characteristic glucosazone 
when boiled with phenylhydrazine in the presence of acetic acid; the osazone 
crystallizes from the hot solution. Glucose reduces metallic oxides in 
alkaline solution. It undergoes alcoholic fermentation with yeast and acid 
fermentation with certain bacteria. 

CH 2 OH CH 2 OH 






Dextrose. Levulose. 

Levulose (fructose) is a ketose and is found associated with dextrose 
in many fruits, the mixture probably being produced by the hydrolysis of, or 
preceding the synthesis of, cane-sugar. It may be prepared by the hydrolysis 
of inulin and, along with dextrose, by the inversion of cane-sugar on boiling 
with dilute mineral acids or through the action of specific enzymes. It is 


levorotatory, [a] d = 92. Levulose may be crystallized with difficulty in 
needles. It has a sweet taste. It reduces alkaline solutions of the 
metallic oxides, but not so much as dextrose, and yields an osazone identical 
with glucosazone. It undergoes fermentation, but less readily than dextrose. 

Galactose is obtained with dextrose from milk-sugar or lactose on 
boiling with dilute mineral acids. It is less soluble in water than levulose 
or glucose. It reduces metallic oxide in alkaline solution, forms a charac- 
teristic osazone which melts at 193-4 C. and it undergoes slow fermentation 
by yeast. It is dextrorotatory. 

It is also obtained on hydrolysis of cerebrin, a glucoside occurring in 
nervous tissue. 

Maltose (malt -sugar) is produced by the action of amylolytic enzymes 
on starch and glycogen. It crystallizes in small needles, is strongly dextro- 
rotatory, [a] d = +140.6, reduces alkaline copper solutions much feebler 
than dextrose, and does not reduce bismuth oxide. It forms a characteris- 
tically crystalline osazone, melting at 206 C. It is readily soluble in water 
and only slightly soluble in alcohol. Maltose is not so sweet as cane-sugar. 
It does not undergo alcoholic fermentation with yeast unless first split into 
dextrose. On boiling with dilute mineral acids or through the action of 
inverting enzymes, it is hydrolyzed into dextrose. 

Saccharose (cane-sugar) is obtained from many plants, such as the 
sugar beet and sugar cane, and from the sap of certain trees, as the sugar 
maple. It crystallizes in prisms, is soluble in water, and only very slightly 
soluble in alcohol. Cane-sugar is not directly fermentable by yeast. It is 
dextrorotary. Saccharose has no reducing action on alkaline copper solution 
the dextrose and levulose yielded on inversion probably being united 
together by the aldehyde and ketone radicals, respectively. Similarly, it does 
not form an osazone. In strong solutions, saccharose acts as a food pre- 
servative against bacterial or other decomposition through organic agencies. 
On boiling with dilute mineral acids or through the action of inverting en- 
zymes, one molecule of saccharose yields one molecule of dextrose and one 
molecule of levulose. 

Lactose (milk-sugar) is present as the chief carbohydrate of milk. It 
may be separated from the whey the product remaining after skimming 
milk and precipitating the proteins therein. It can be prepared in large 
hard crystals. It is much less soluble in water than cane-sugar, and has but 
a slightly sweet taste. Lactose is strongly dextrorotatory, [a] d = +52.5. 
It reduces alkaline copper solution and forms a characteristic osazone. It 
is not fermented by ordinary yeast; certain bacteria easily convert it into 
lactic and other simple organic acids. The inverted milk-sugar undergoes 
alcoholic fermentation readily, and kumiss and kephir, made from mare's 
and cow's milk, respectively, are prepared in this way. On hydrolyzing by 
boiling with mineral acids or through the action of inverting enzymes, the 
lactose is split into dextrose and galactose. 



Dextrins are a series of intermediate poly-saccharides between the di- 
saccharides and the starches. They are non-crystalline, are soluble in 
water, and are precipitated on the addition of alcohol in excess. They are 
dextrorotatory and are not fermented by yeast. Their power to reduce 
alkaline copper solution has been questioned, but they yield osazones which 
are relatively soluble. They have a slightly sweet taste. The more com- 
plex dextrins give a red reaction with iodine. 

Starch is found in various parts of plants, especially in the tubers and 
seeds. It is a form of storage carbohydrate, and serves as a source of ma- 
terial for the development of the young plant. Starch is obtained commer- 
cially from potatoes, rice, corn, wheat, sago, and the like. It constitutes the 
greater proportion of our food. 

Starch as obtained is a soft white powder which on microscopic examina- 
tion is found to consist of small granules. These are often characteristic in 
shape and size according to the origin of the material. The granules appear 
to be built up of concentric layers of two varieties of starch. The more sol- 
uble form, known as amylose, is ensheathed by the less soluble variety of 
starch, the amylopectin. This sheath is ruptured by boiling the aqueous sus- 
pension of starch granules and an opalescent solution or starch paste is 
obtained. On standing in dilute solution, the opalescent material settles to 
the bottom, but the clear fluid above still gives the blue reaction with iodine. 
This color is characteristic for starch; it disappears on heating, but returns 
when the liquid cools. Starch will not diffuse through a semi-permeable 
membrane. On boiling with dilute mineral acids starch is hydrolyzed to dex- 
trose. The dextrins and maltose are formed as intermediate products. 
With amylolytic enzymes, the change practically only goes as far as the 
maltose stage. 

Glycogen (animal starch) is the reserve form of carbohydrates in 
animals. It is synthesized from dextrose and can again be hydrolyzed to 
dextrose for transportation or for oxidation to yield energy to the tissues. 
The following table shows the per cent, and distribution of glycogen in the 
various tissues of the dog (Schondorff) : 


Per cent, glycogen 

Per cent, of total 


o . 004 i 

o . 01 <c 

Liver . . 




O 7 ^OO 

A A , 2 "? 



o . 2024 


Skin . . 

o . 08 so 

4. 40 


O 2T.1 

O 17 


o 1 084. 



It occurs in relatively large amounts in some invertebrates, especially 
in moluscs and in intestinal worms. The muscles and reproductive organs of 
oysters, clams, and scallops are very rich in this substance. 

Glycogen resembles starch in forming opalescent solutions. It may be 
prepared from the liver or muscle of a freshly killed animal by boiling the 
tissue to coagulate the proteins, grinding with sand, boiling with water 
slightly acidified with acetic acid and precipitating the nitrate with an excess 
of alcohol; dilute or concentrated solutions of caustic alkalies may be used 
to extract all the glycogen. Glycogen is a white, tasteless, and amorphous 
powder. It gives a maroon color with iodine, and does not reduce alkaline 
copper sulphate solution. It is completely precipitated by saturating its 
solution with solid ammonium sulphate, by tannic acid, or by ammoniacal 
basic lead acetate. On hydrolysis with mineral acids or on digestion with 
amylolytic enzymes it yields the same series of products as ordinary starch. 

Inulin is the reserve carbohydrate of the Composites, occurring in the 
tubers of the artichoke and dahlia and in the roots of the dandelion and bur- 
dock. On hydrolysis with acids or the enzyme inulase, it yields levulose. 
Inulin is slightly soluble in cold and easily soluble in hot water. It is precipi- 
tated from its solution by an excess of alcohol. The digestive enzymes of the 
body do not act on inulin. 

Lichinin is obtained from the Cetraria Islandica (Iceland moss). It forms 
a difficultly soluble jelly in cold water and an opalescent solution in hot water. 
On hydrolysis with dilute acids, it yields dextrines and dextrose. The 
ordinary digestive enzymes have no action on lichinin. 

Cellulose forms a large portion of the cell wall or the woody structure 
of plants. It is extremely insoluble. Chemically, it is more complex than 
the common starch molecule. The hydrochloric and hydrofluoric acid 
extracted (ash-free) filter-papers and absorbent cotton are examples of prac- 
tically pure cellulose. 


Salt. The inorganic principles of the human body are numerous. 
They are derived, for the most part, directly from food and drink and pass 
through the system unaltered. Some radicals are newly formed by oxi- 
dation within the body, as, for example, a part of the sulphates and car- 
bonates from the sulphur of the proteins and the carbon of protein, fat, and 

Much of the inorganic saline matter found in the body is a necessary 
constituent of its structure, as necessary in its way as protein or any other 
organic principle. Another part is important in regulating or modifying 
various physical processes, as absorption, solution, and the like. A part 
must be reckoned only as matter which is, so to speak, accidentally present, 
whether derived from the food or the tissues, and which will, at the first 


opportunity, be excreted from the body. The principal salts present in 
the body are: 

Sodium and Potassium Chlorides. These salts are present in nearly all 
parts of the body. The former seems to be especially necessary, judging 
from the instinctive craving for it on the part of animals in whose food it 
is deficient, and from the condition which is consequent on its withdrawal. 
The quantity of sodium chloride in the blood is greater than that of all its 
other saline ingredients taken together, but it is present chiefly in the fluids 
of the body. In the tissues, the muscles for example, the quantity of sodium 
chloride is less than that of the chloride of potassium, which forms a constant 
ingredient of protoplasm. 

Calcium Fluoride. It is present in minute amount in the bones and 
teeth, and traces have been found in the blood and some other fluids. 

Calcium, Potassium, Sodium, and Magnesium Phosphates. These phos- 
phates are found in nearly every tissue and fluid. In some tissues the bones 
and teeth tricalcium phosphate exists in very large amount. The phos- 
phate of calcium is intimately incorporated with the organic basis or matrix, 
but it can be removed by acids without destroying the general shape of the 
bone. After the removal of its inorganic salts, a bone is left soft, tough, 
and flexible. 

Potassium and sodium phosphates, with the carbonates, maintain the 
alkalinity of the blood. 

Calcium Carbonate. It occurs in bones and teeth, but in much smaller 
quantity than the phosphate. It is found also in some other parts. The 
small concretions of the internal ear of some fishes (otoliths) are composed 
of crystalline calcium carbonate, and form the only example of inorganic 
crystalline matter existing as such in the body. 

Potassium and Sodium Carbonates and Sulphates. These are found in 
the blood and most of the secretions and tissues. 

Silicon. A very minute quantity of silica exists in the urine and in 
the blood. Traces of it have been found also in bones, hair, and some 
other parts. 

Iron. The especial place of iron is in hemoglobin, the coloring- matter 
of the blood, of which a full account will be given with the chemistry of the 
blood. Iron is found, in very small quantities, in the ashes of bones, mus- 
cles, and many tissues, and in lymph and chyle, albumin of serum, fibrin, 
bile, milk, and other fluids. 

Iodine occurs as an iodized protein in the thyroid gland. Biologically, 
it is found as a tri-iodotyrosin in sponges and the Gorgonian corals. 

Water. Water forms a large proportion, more than two-thirds, of 
the weight of the whole body. Its relative amount in some of the principal 
solids and fluids of the body is shown in the following table (from Robin 
and Verdeil) : 


Quantity of Water in Per Cent. 

Teeth 10.0 Bile 88.0 

Bones 13.0 Milk 88.7 

Cartilage 55 -o Pancreatic juice. ... 90.0 

Muscles 75- Urine 93-6 

Ligament 76.8 Lymph 96.0 

Brain 78.9 Gastric juice 97-5 

Blood 79 . 5 Perspiration 98.6 

Synovia 80 . 5 Saliva 99-5 

In all the fluids and tissues of the body blood, lymph, muscle, gland, 
etc. water acts the part of a general solvent, and by its means alone circula- 
tion of nutrient matter is possible. It is the medium also in which all fluid 
and solid aliments are dissolved before absorption, as well as the means by 
which all, except gaseous, excretory products are removed. All the various 
processes of secretion, transudation, and nutrition depend of necessity on 
its presence for their performance. 

The greater part, by far, of the water present in the body is taken into 
it as such from without, in the food and drink. A small amount, however, 
is the result of the chemical union of hydrogen with oxygen in the oxidations 
of the body. 

The loss of water from the body is intimately connected with excretion 
from the lungs, skin, and kidneys, and, to a less extent, from the alimentary 
canal. The loss from these various organs may be thus apportioned (quoted 
by Dalton from various observers): 

From the alimentary canal (feces) 4 per cent. 

From the lungs 20 per cent. 

From the skin (perspiration) 30 per cent. 

From the kidneys (urine) 46 per cent. 


Under some conditions the loss of water from the alimentary canal may 
be enormously increased, as in acute diarrheas. In young children and 
babies in particular this fact is often not realized and not enough water is 
given by the mouth to supply the loss. The result is a considerable 
concentration of the blood and tissues, a relative dessication that may 
prove very injurious. 




This list will serve as basal for the guidance of students and teachers. 
The experiments listed are to be supplemented by technical laboratory 
guides and references to fuller discussion in the literature. 


i. Preparation of Proteins. The most convenient source of proteins 
for laboratory work are blood serum, egg white, or commercial preparations 
of the milk protein casein. Protein may also be prepared from various 
plant seeds, especially cereals. Hempseed contains a globulin, edestin, 
which is very easily isolated in the laboratory. 

a. Preparation of Edestin. Grind up some hemp-seed in an ordinary 
meat chopper and extract the resulting meal with 5 per cent, salt solution, 
warming to 60. The solution should not be heated above 65 because 
the protein will be coagulated. Filter while hot. On cooling slowly the 
edestin will crystallize out. Examine some of the precipitate with a micro- 
scope and sketch the crystals. The edestin is soluble in 10 per cent, salt 
solution without warming, and solutions for laboratory use can be prepared 
in this way. 

b. Preparation of Egg Albumin. The yolk should be separated from 
the white of fresh eggs and the reticulum in the egg white broken up with 
a wire egg-beater. Egg white can then be diluted as desired and the pre- 
cipitate globulin filtered off. Crystals of ovalbumin can be prepared as 

The egg white, beaten as directed, is strained through gauze and an 
equal volume of saturated ammonium sulphate solution is added. After 
twenty-four hours the globulin precipitate is filtered off and concentrated 
ammonium sulphate solution added until the mixture becomes turbid. 
Then distilled water is added very carefully until turbidity has disappeared. 
The solution is then acidified with acetic acid, which has been saturated 
with ammonium sulphate, until a precipitate is obtained." The precipitate 
is at first amorphous, and on standing becomes crystalline. Examine the 
crystals under the microscope and sketch them. 

c. Other Protein Crystals. Crystals of hemoglobin may be demon- 
strated by adding a drop of ether to diluted dog blood on the microscope 
slide and allowing the mixture to dry around the edge. Hemoglobin crys- 
tals may be observed under the microscope to have formed where the solu- 
tion has concentrated and dried. 

Crystals of seralbumin and of lactalbumin can be obtained in essen- 
tially the same manner already described for ovalbumin. 



2. Elementary Composition of the Proteins. a. Nitrogen. Make 
an intimate mixture of some dry protein, preferably a casein preparation, 
with sodalime and place it in a dry test-tube. Warm gently over a Bunsen 
flame. Hold a piece of moistened red litmus-paper over the mouth of 
the test-tube. The ammonia split off from the protein will color the 
litmus blue. 

Warm together carefully in a dry test-tube a few particles of dry protein 
and a small cube of metallic sodium. (Do not place the tube in the flame.) 
When the fusion is complete and the tube is cooled somewhat, plunge the 
end into a small amount of water in a casserole. The glass of the test-tube 
will probably break. When the fused mass has dissolved, filter, and to the 
filtrate add a few drops of ferric chloride and ferrous sulphate solution. 
On acidifying with hydrochloric acid a precipitate of Prussian blue is ob- 
tained. Sodium ferricyanide is formed in the reaction and in consequence 
gives a Prussian blue with the excess of iron present. 

b. Carbon. Place some desiccated casein in the end of a piece of glass 
tubing, tap it down gently so that the lumen of the tube will not be obstructed. 
Heat the casein gently over a small Bunsen flame, inclining the tube so that 
there will be a slight current of air passing upward through it. The casein 
will char, indicating the presence of carbon. 

c. Hydrogen. Note the clear fluid that has condensed in the upper 
portion of the tubing from the preceding experiment. If a little anhydrous 
copper sulphate is introduced into the tube, the fluid of condensation coming 
in contact with it will become blue, indicating that water has been formed 
in the charring of the casein. Hydrogen in protein has been oxidized to form 

d. Sulphur. Boil some casein or some egg-white solution with sodium 
hydroxide after adding a few drops of lead acetate solution. The presence 
of sulphur is shown by the formation of a black-lead sulphide. On adding 
hydrochloric acid the lead sulphide formed will be decomposed and the odor 
of hydrogen sulphide will be noted. 

e. Phosphorus. Heat some casein, preferably in a nickel crucible, with 
a fusion mixture composed of three or four parts of caustic soda and one part 
of potassium nitrate, warming cautiously until the mass becomes colorless. 
Dissolve the residue when cool in a small volume of water, neutralize and 
acidify with nitric acid slightly, and add about 5 c.c. of ammonium molyb- 
date solution. Warm for some minutes at 80. A yellow precipitate of 
ammonium phosphomolybdate is obtained. 

3. Color Reactions of the Proteins. a. Millon's Reaction. To about 
5 c.c. of a dilute solution of egg albumin in a test-tube add a few drops of 
Millon's reagent. A white precipitate forms which turns red when heated. 
This test can be used with advantage on solid proteins. In this case the 


reagent is added to suspensions of the solid substance. Such proteins as are 
not precipitated by the mineral acids yield a red solution instead of a red 
precipitate. Millon's reagent consists of one part mercury dissolved in two 
parts by weight of concentrated nitric acid; the resulting solution is diluted 
with two volumes of water. 

This reaction is due to the presence of the hydroxyphenyl group or 
C 6 H 5 OH in the protein molecule. Accordingly, certain non-protein sub- 
stances give this reaction; i.e., tyrosine, phenol (carbolic acid), thymol, etc. 
The reaction given by the protein is due to the presence of the amino acid 
tyrosine, and it is evident that the test is really an indication of the presence 
of the tyrosine complex in the protein molecule. 

b. Xanthoproteic Reaction. To 2-3 c.c. of egg-albumin solution or of 
some dry casein in the test-tube, add concentrated nitric acid and heat until 
the protein dissolves, forming a yellow solution. Cool the solution and care- 
fully add ammonium hydroxide in excess. The yellow color changes to an 
orange. This reaction is due to the presence in the protein molecule of the 
phenyl group in phenyalanine, tyrosine, or tryptophane; with the phenyl 
group nitric acid forms certain nitro-derivatives of benzene. 

c. Adamkiewicz or Hopkins-Cole Reaction. Mix a couple of c.c. of con- 
centrated sulphuric acid with 4 or 5 c.c. of glacial acetic acid in a test-tube. 
Add a few drops of egg-albumin solution and warm gently. A reddish- 
violet color is produced. This reaction is due to the presence of trypto- 
phane in the protein and the test depends on the presence of glyoxylic acid 
(CHOH 2 COOH) in the acetic acid. The Hopkins-Cole reagent, a glyoxylic 
acid solution, may be used instead of the glacial acetic acid. The reagent 
is prepared by adding sodium amalgam to a saturated solution of oxalic 
acid and allowing the mixture to stand until the evolution of gas ceases. 
In making the test the protein solution and Hopkins-Cole reagent are mixed 
thoroughly in a test-tube, and concentrated sulphuric acid poured gently 
into the tube which has been inclined somewhat so that it forms a layer in 
the bottom of the test-tube. The acid and protein solutions will be strati- 
fied and a reddish-violet ring is developed where the two fluids come in 

This reaction is due to the presence of tryptophane in the protein mole- 
cule. Gelatin does not respond to this test, for it does not yield this sub- 
stance as a cleavage product. 

d. Liebermann's Reaction. Add a few drops of egg-white solution or a 
little dry casein to about 5 c.c. of concentrated hydrochloric acid in a test- 
tube and boil the mixture until a pinkish-violet color results. It was for- 
merly thought that this reaction indicated the presence of a carbohydrate 
group in the protein molecule, but this is now considered uncertain. 

e. Biuret Reaction. To 2 or 3 c.c. of egg-white solution in a test-tube an 


equal volume of concentrated potassium hydroxide solution is added and 
mixed thoroughly. Very dilute (2 per cent.) copper sulphate solution is 
added until a purplish-violet or pinkish-violet color is produced. This 
reaction is given by substances containing twoamino groups in the molecule, 
these groups being joined directly together or through a single atom of 
nitrogen or carbon. Non-protein substances that contain the necessary 
groups will of course respond to this test, which derives its name from the 
fact that it is given by biuret, a substance formed on heating urea to 180. 

NH 2 

NH 2 CO 

2 C=0 = NH + NH S 
\ \ 

NH 2 CO 

NH 2 

Urea. Biuret. Ammonia 

Proteins give this reaction since there are more than one CONH 2 group 
fn the protein molecule. Proteoses and peptones give a pink biuret re- 
action, gelatin a rather blue reaction, and the ordinary proteins a purple. 

/. Molisch Reaction. This reaction is really a carbohydrate test, but is 
given by some proteins and interpreted as indicating that such proteins 
contain a carbohydrate moiety. The test is made as follows : 

Place about 5 c.c. of the solution to be tested in a test-tube, and add a 
couple of drops of a 15 percent, alcoholic solution of a-naphthol. Incline 
the tube and pour very carefully down the side about 5 c.c. of concentrated 
sulphuric acid so that the two solutions are stratified. A blue or violet-red 
ring is obtained in the area of contact of the solutions. 

4. Precipitation Reactions of the Proteins. a. Precipitation with 
Concentrated Mineral Acids. Prepare four test-tubes which contain about 
5 c.c. of egg-white solution. To these respectively add drop by drop con- 
centrated sulphuric acid, hydrochloric acid, nitric acid, and acetic acid. 
Note that the mineral acids precipitate the protein. The precipitation with 
nitric acid is a frequently used protein reaction, and when carried out as 
follows is known as Heller's ring test. The solution to be tested is placed 
in a test-tube, the tube is inclined and about 5 c.c. of concentrated nitric 
acid is poured carefully down the side of the tube so that the solution and 
acid stratify. A white zone of precipitated protein is obtained between the 
strata. An instrument known as the albumiscope has been devised to 
facilitate the making of the ring tests. Heller's ring test is most commonly 
used to determine the presence of protein in urine. 


b. Precipitation with Heavy Metals. Proteins form insoluble compounds 
with the metals when mercuric chloride, lead acetate, copper sulphate, 
silver nitrate, etc., are added to protein solutions. 

c. Acetic Acid and Potassium Ferrocyanide Test. To about 5 c.c. of egg- 
white solution in a test-tube add five to ten drops of acetic acid and then 
potassium ferrocyanide drop by drop until a precipitate forms. This 
test is very delicate. 

d. Precipitation with the Alkaloidal Reagents. Prepare six tubes contain- 
ing about 3 c.c. egg-white solution. To the first add picric acid drop by 
drop until excess of the reagent has been added, noting the changes with 
care. Repeat the experiment with trichloracetic acid and tannic acid. 
Acidify the remaining tubes with hydrochloric acid, and repeat the experi- 
ment with phosphotungstic acid, phosphomolybdic acid, and potassium 
mercuric iodide. 

e. Heat Coagulation. Take about 10 c.c. of egg-white solution in a test- 
tube and heat to boiling. Then add a few drops of dilute acetic acid. The 
protein will be coagulated. The acetic acid should be added after heating, 
since otherwise acid metaprotein might be formed. The presence of 
some neutral inorganic salts tends to give a sharper test. The addition of 
the acid also will dissolve the earthy phosphates which are often precipi- 
tated from the urine on heating. Proteoses, peptones, the casein of milk, 
and a few other proteins are not coagulated by heat. 

/. Precipitation by Alcohol. Add some 95 per cent, alcohol to a test-tube 
containing about 3 c.c. of egg-white solution. The protein is precipitated, 
and on standing it is coagulated so that it can no longer be dissolved in 
neutral solvent. 

g. Salting-out Experiments. Add to some diluted blood-serum in a small 
beaker, crystals of magnesium sulphate until no more of the salt will go 
into solution. After standing for a few minutes, filter and test the filtrate 
and residue for protein by some of the precipitation or color reactions given 
above. It is found that the filtrate still contains some protein. Further, 
that this protein can be precipitated on adding a few drops of dilute acetic 
acid. When the blood serum is similarly saturated with ammonium 
sulphate, there will be no protein found in the filtrate. If to the blood 
serum an equal volume of saturated ammonium sulphate solution is 
added, the result will be the same as that already obtained with mag- 
nesium sulphate. Some proteins then are precipitated on saturating 
their solutions with magnesium sulphate or by adding an equal volume 
of saturated ammonium sulphate solution; albumins, globulins, and 
proteoses, however, are all precipitated by saturation with the more 
soluble ammonium sulphate. 




5. Properties of Albumins and Globulins. Try out the solubility 
and the precipitation tests indicated in the following table for a solution of 
ovalbumin, and on edestin furnished by the instructor. 

Soluble in 












Very dilute acid 


On saturation 
with NaCl* 

On saturation 
with MgSO 4 * 

On half-saturatif 
with (NH 4)2804" 

On saturation 
with (NH 4 ) 2 SO 

Alcohol in exces 


Alcohol J 






6. Keratin. Horn shavings are most conveniently used for the experi- 
ments with keratin. 

a. Try the solubility of keratin in water, 10 per cent, salt solution, dilute 
hydrochloric acid, and dilute potassium or sodium hydroxide. 

b. Make a test for loosely combined sulphur as in experiment 2, d, 
page 1 06. 

c. Try Millon's reaction and the biuret reaction, putting the undissolved 
shavings directly into the reagent. 

d. Try the solubility of keratin in the artificial gastric and pancreatic 
juice furnished by the instructor. 

7. Collagen. The tendo achillis of the ox may be used for the prepara- 
tion of collagen. 

a. Clean the tendon and cut it into small pieces. Wash the pieces in 
dilute salt solution in order to remove the soluble protein, and then wash 
with distilled water. Transfer the pieces of washed tendon to a flask and 
add 100 c.c. of saturated lime-water and same amount of distilled water. 
The flask should be shaken at intervals for twenty-four hours. The lime- 
water dissolves the mucoid in the tendon. Filter off the pieces of tendon 
and save the filtrate for a later experiment. The residue of the tendon con- 
sists of the albuminoid collagen and a little elastin. We may consider the 
tests to follow as being made upon collagen. 

b. Cut the collagen into very fine pieces and try the solubility as in 6 a 

* If not precipitated, acidify and note result. 

t See page 89. 

J On standing under alcohol. 


c. Test for loosely combined sulphur in collagen. Heat with the alkali 
until the large piece of collagen used is partly decomposed, then add one or 
two drops of lead acetate and again heat to boiling. 

d. Try Millon's reaction, the biuret test, the xanthoproteic reaction, and 
the Hopkins-Cole reaction. 

e. Formation of gelatin from collagen. Transfer the remainder of the 
collagen to a casserole, fill about two-thirds with water, and boil for several 
hours, replacing enough of the water that is lost by evaporation to keep the 
pieces well covered. Filter and cool. Collagen is transformed into gelatin 
and the characteristic gel is obtained. Try this experiment also with some 
cartilage from the trachea and with some 0.2 per cent. HC1 extracted bone. 

/. The properties of gelatin. Try the solubility as in a above on some 
gelatin furnished by the instructor. Try the solubility also in hot water. 

g. Try the tests for loosely combined sulphur. Try Millon's Hopkins- 
Cole, and the biuret reactions. Try the solubility in artificial gastric and 
pancreatic juices. 

8. Elastin. a. Preparation of Elastin. Cut the ligamentum nuchce of, 
the ox into strips and run it through a meat chopper. Wash the finely 
divided material with salt solution and in running water for some hours. 
Transfer it to a flask and add about 200 c.c. of half-saturated lime-water and 
extract for forty-eight hours. Filter off the lime-water which has dissolved 
the mucoid present, saving the filtrate, and wash the residue and tendon with 
water. Boil the material in dilute acetic acid for some hours to convert the 
collagen present into gelatin. Wash the residue thoroughly with water. It 
may be dried by washing it with boiling alcohol, pressing it out between 
filters, and manipulating it in the air. 

b. Try the solubility of elastin as in a. Test for loosely combined 
sulphur. Try Millon's, biuret, and the Hopkins-Cole reactions. Try the 
solubility in artificial gastric and pancreatic juices. 

c. Make a table comparing the properties of keratin, collagen, and elastin. 


9. Mucoid. a. Unite the lime-water of filtrates obtained in the extraction 
of the tendons in the preceding experiment and acidify them with dilute 
acetic acid until precipitation occurs. The mucoid is precipitated. Avoid 
adding excessive acid or the mucoid will again go into solution. Allow the 
mucoid precipitate to settle and decant the supernatant fluid and filter off 
the precipitate. 

b. Try the biuret test on a portion of the mucoid. 

c. Place the remainder of the mucoid in a beaker, add about 25 c.c. of 
water and 2 c.c. of dilute hydrochloric acid; boil until the solution becomes 
dark. To a portion of the mixture add a few drops of barium chloride. A 


white precipitate shows the presence of sulphate. Neutralize to litmus-paper 
with solid potassium or sodium hydroxide and test for sugar with Fehling's 
solution (see Experiment 12, d). The mucoid has been split by boiling with 
acid into protein, protein cleavage products, and carbohydrate or a reducing 
substance. The presence of oxidized sulphur in the molecule has also 
been shown. 


10. Metaproteins. a. Acid Metaproteins or Acid Albuminate. Acid 
metaprotein or acid albumin may be prepared as follows: 

Dilute solution of white of egg with several volumes of .4 per cent, hydro- 
chloric acid. Allow it to stand for some time at 40 Centigrade. Filter and 
neutralize the filtrate. A precipitate of acid metaprotein is obtained. The 
acid albuminate then is insoluble in neutral dilute salt solutions, but it dis- 
solves in acidified solutions. Filter off some of the precipitated acid albumin- 
ate and test it for loosely combined sulphur. 

b. Alkali metaprotein is formed on treating proteins with alkali. To 
some undiluted egg white in an evaporating dish add sodium hydroxide solu- 
tion slowly with constant stirring. The mixture forms a stiff gel known as 
Lieberkuhn's jelly. Wash the gel, which has been broken into small pieces, 
with running water until the excess of alkali is removed. Warm it in a small 
amount of water and dissolve by heating gently. Neutralize the solution 
carefully with acid, noting the odor of the hydrogen sulphide that is given off. 
The precipitate which appears when the neutral point is reached is alkali 
metaprotein or alkali albuminate. Filter off the precipitate, wash it in 
water, and try the test for loosely combined sulphur. A weak reaction or 
negative result shows that the loosely combined sulphur has been split off by 
treating the protein with the alkali, a change which has not occurred in the 
formation of the acid albuminate above. 


11. Proteose and Peptone. Commercial proteose- peptone prepara- 
tions, such as Witte peptone or Armour's peptone, may be employed for 
the separation of proteoses and peptones. 

a. Take about 5 grams of the proteose-peptone mixture and dissolve it in 
100 c.c. of water. 

Try the biuret reaction, Millon's reaction, and Heller's ring test. Do 
the proteoses and peptones coagulate on heating ? 

b. Place the remainder of the solution in the beaker and add dry ammonium 
sulphate in excess. Note that before the solution is completely saturated with 
the salt, the precipitation of the primary proteoses (proto proteose and hetero 
proteose). Completely saturate the solution with the ammonium sulphate, 
warming it gently to facilitate the separation. At full saturation the second- 


ary proteoses (deutero-proteoses) are precipitated. The peptones remain 
in solution. Try the biuret test on the precipitate and on the filtrate con- 
taining the peptone, in the latter instance making the solution strongly alka- 
line with solid sodium or potassium hydroxide. 

d. From what you have learned of the properties of the derived proteins 
in the text and in the laboratory, prepare a chart (Exp. 5) in which the 
properties of these substances are indicated. Compare the results in this 
chart and the results in this table with the similar one that you made for 
the albumins and globulins 


12. Starch. a. Examine under the microscope and sketch the starch 
granules obtained by grinding some potato scrapings in a mortar with a 
little water; examine and sketch also the granules of corn, wheat (flour), 
and arrowroot starch. 

b. Starch Paste. Make a suspension of i gram of arrowroot starch in a 
little distilled water by grinding in a mortar, and pour slowly into some 
boiling water. Heat for a few minutes longer, cool and make up to 
100 c.c. 

c. Iodine Test. Shake up three or four drops of dilute iodine solution 
with 2 c.c. starch. A deep blue color appears. The color is discharged in 
dilute alkali and reappears on acidifying again. Heat also discharges 
the color. 

d. Fehling's Test. Fill a test-tube about a fourth full of Fehling's 
solution and heat to boiling for a minute or two. Add a few drops of starch 
paste. The red precipitate of copper (cuprous) oxide should not be obtained, 
for pure starch does not reduce Fehling's solution. 

e. Hydrolysis of Starch. Boil starch solution with 5 per cent, sulphuric 
acid for fifteen minutes. Test with Fehling's solution, first neutralising the 
excess of acid. A copious precipitate of cuprous oxide shows that the starch 
has been converted to reducing sugar. 

13. Dextrins. Make a 5 per cent, solution of dextrin in distilled water 
and try: 

a. Iodine Test. This gives a red which is characteristic. 

b. Fehling's Test. 

14. Dextrose. Test a 5 per cent, solution of dextrose: 

a. Iodine Test. No reaction. 

b. Fehling's Test. 

15. Glycogen. Use i per cent, solution of glycogen. Note the char- 
acteristic opalescence of the solution. 

a. Iodine Test. A wine-red, somewhat like that given by dextrin. 

b. Fehling's Test. Glycogen does not reduce the copper solution. 

c. Hydrolysis. Test as in e. The glycogen is hydrolyzed to dextrose. 



16. Neutral Fat. a. Melting-point. Compare neutral olive oil, some 
fresh rendered lard, and some tallow. The former is fluid at ordinary 
room temperature. Determine the melting-points of the lard and of the 
tallow by the method of Wiley. Fill a test-tube one-half full of water and 
add a two-inch top layer of alcohol. Prepare a thin flake of fat and suspend 
it in the test-tube at the dividing line of the water and alcohol. Insert the 
bulb of a thermometer at the same level. Mount the test-tube with the 
thermometer in a beaker on a ring stand, fill the beaker with water above the 
level of the content of the test-tube, and gradually heat with stirring of the 
water in the beaker. At the melting temperature the flake of fat will run 
into a round drop. 

b. Solubility. Fat is insoluble in water, but soluble in acetone, ether, 
chloroform, benzol, and in alcohol. 

c. Saponification. Heat some fat in an evaporating-dish, add sodium 
hydrate, and boil. Saponification takes place. The soap is soluble in water. 
Add 25 per cent, sulphuric acid to some of the soap, the fatty acid is liberated 
and collects on the surface of the solution. 

17. Fatty Acids. Collect some of the fatty acids, wash to remove 
excess of sulphuric acid, and dissolve in ether. 

a. Acid Reaction. Add an ether solution of the fatty acid to neutral 
litmus, or to faintly alkaline phenolphthalein. The former turns red, and 
the red of the alkaline solution of the latter is discharged. 

b. Acrolein Test. Evaporate the ether from 2 c.c. of the solution, add 
potassium bisulphate crystals to the acid in a test-tube, and raise to a high 
heat over a Bunsen. No acrolein is given off. Repeat on neutral fat and 
on glycerin. Both liberate the irritating fumes of acrolein. 

18. Emulsification. a. Shake up neutral olive oil and water, no 
emulsion is formed and the oil quickly separates. 

b. Add a couple of drops of fatty acid, a very good but temporary emul- 
sion is now formed. 

c. Use rancid fat, a temporary emulsion is formed. 

d. Add a little soap to each of the above. A good permanent emulsion 
is now formed, but best in c. 

19. Lipoids. a. Grind some pig's or calf's brain with ether in a 
mortar, place in a flask with sufficient ether to make a thin suspension of 
the material and set aside until the undissolved material has sedimented 
completely to the bottom. Decant the clear ether and add acetone until 
the lecithins have been precipitated. Cholesterol will crystallize from the 
filtrate on spontaneous evaporation of the latter. Sketch the cholesterol 

b. Show the presence of nitrogen in lecithin (see Exp. 2 a). 

FATS 115 

;. Try the acrolein test as in Exp. 17 b. 

d. Fuse some lecithin in a metal crucible with a fusion mixture of 3 
parts of caustic potash and i part of potassium nitrate. Dissolve in a 
small volume of water, acidify slightly with nitric acid, add a few drops of 
ammonium molybdate solution, and warm to 75 C. for a few minutes. A 
yellow precipitate of ammonium phosphomolybdate indicates the presence 
of phosphorus in the lecithin. 

e. Try to saponify some cholesterol as in Exp. 16 c. As cholesterol is 
not a fat, saponification does not take place. 

20. The Salts. Coagulate the protein in 10 grams of chopped meat or 
25 c.c. of blood by boiling for a few minutes with 25 c.c. of water to which a 
few drops of acetic acid have been added. Filter off the coagulated protein, 
wash the precipitate on the paper with a very little hot water, and add the 
washings to the original filtrate. The coagulum should filter off quickly 
and the filtrate should be perfectly clear; otherwise repeat the experiment. 
Make the following tests: 

a. Chlorides. Acidify a small portion of the filtrate with nitric acid 
and add a few drops of silver nitrate solution. A white precipitate, which 
dissolves on adding ammonia and reappears on acidification with nitric 
acid, shows the presence of chlorides. 

b. Sulphates. Acidify a portion of the filtrate with hydrochloric acid 
and add a few drops of barium chloride solution. A white precipitate of 
barium sulphate indicates that sulphates are present. A much stronger 
reaction can be obtained when the ash or alkali fusion of a tissue is tested, 
the sulphur in the protein then having been oxidized to a sulphate. 

c. Phosphates. Acidify with nitric acid and then add a few drops of 
ammonium molybdate solution. Warm in the water-bath at 75 C. for a 
few minutes. A yellow precipitate of ammonium phosphomolybdate indi- 
cates the presence of phosphate. 

d. Calcium. Add a few drops of ammonium oxalate solution to a por- 
tion of the filtrate. A white precipitate of calcium oxalate forms. On 
microscopic examination this is found to consist of characteristic minute 

e. Iron. Acidify with hydrochloric acid and add a few drops of potas- 
sium ferrocyanide. A Prussian blue color indicated the presence of iron. 
Try the reaction on some blood which has been ashed in a crucible and 
dissolved out in a little dilute hydrochloric acid. The iron is present in the 
compound protein, hemoglobin, of the red corpuscles. 

/. Magnesium. Tease out some fibers of frog muscle in a few drops of 
water on a microscope slide and invert a beaker containing a piece of filter- 
paper moistened with ammonia over it. After a few minutes, examine 
under the microscope. Characteristic star-shaped or fern-like crystals of 
ammonium magnesium phosphate will be seen. 



Plate II is reproduced by the kind permission of Dr. Cabot. It illustrates certain 
typical varieties of leucocytes. All are stained with the Ehrlich triacid stain, and drawn 
with camera lucida. Oil immersion objective ^ and ocular No. iii of Leitz. (Cabot.) 

1. Small Lymphocytes. In the cell at the left note the transparent protoplasm; 
in the cell next to it note the very pale pink of protoplasm around the nucleus which 
is deeply stained, especially at the periphery. The next cell has an indented nucleus; 
its protoplasm relatively distinct. The cell on the extreme right shows no protoplasm 
and is probably necrotic. In all note absence of granules with this stain. With basic 
stains a blue network appears in the protoplasm. 

2. Large Lymphocytes. Note the pale stain of nuclei and protoplasm, regularity 
of outline; indented nucleus in one. Every intermediate stage between these and the 
"small" lymphocytes occurs, and the distinction between them is arbitrary. 

3. Polymorphonuclear Neutrophiles. Note the varieties in size and shape of granules, 
the regular staining of the nuclei, the light space around them, their relatively central 
position in the cell. 

. 4. Myelocytes. Note the identity of granules with those just described; the even, 
pale stain of nuclei, their position near the surface (edge) of the cell. The two cells 
figured indicate the usual variations in size of the whole cell. 

5. Eosinophile. Note regular shape, loose connection of granules, their copper 
color, their uniform and relatively large size, and spherical shape. 

6. Eosinophilic Myelocyte. Note similarity to the ordinary myelocytes b, except 
as regards granules. Colors of granules may be, as in e, ordinary eosinophile. 





neutrophiles t _ __^H 


dBHI Small Lymphocytes 

Large Lymphocytes 


^^HL Eosinophilic 
Y"* Myelocyte 

Varieties of Leucocytes 

R. C. Cabot fee. 



THE blood is the fluid medium from which all the tissues of the body are 
nourished. By means of the blood, materials absorbed from the alimentary 
canal as well as oxygen taken from the air in the lungs are carried to the 
tissues, while substances which result from the metabolism of the tissues are 
carried to the excretory organs to be removed from the body. The blood 
acts as a medium of exchange between the various tissues themselves. A 
good example is the activity of the blood in regulating the reaction of 
the body in balanced neutrality. The blood is also an important factor 
in the regulation of the body temperature. 

The blood is a somewhat viscid fluid, and in man and in all other 
vertebrate animals, with the exception of the two lowest, is red in color. 
The exact color of blood is variable; that taken from the systemic arteries, 
from the left side of the heart and from the pulmonary veins is of a bright 
scarlet hue; that obtained from the systemic veins, from the right side of 
the heart, and from the pulmonary artery is of a much darker color, which 
varies from bluish-red to reddish-black. At first sight the red color appears 
to belong to the whole mass of blood, but on further examination this is 
found not to be the case. In reality blood consists of an almost colorless 
fluid, called plasma or liquor sanguinis, in which are suspended numerous 
minute masses of protoplasm, called blood corpuscles. The corpuscles are 
of the two varieties, the white ameboid corpuscles, or leucocytes, and the 
red corpuscles, erythrocytes. The latter compose by far the larger mass of 
blood-cells. They contain the red pigment, hemoglobin, to which the color 
of the blood is due. 

The plasma or fluid part of the blood is a remarkably complex chemical 
mixture. It is kept in constant rapid circulation through the blood vessels 
of the body and is, therefore, thoroughly mixed and homogeneous in 

Quantity of the Blood. The quantity of blood in any animal under 
normal conditions bears a fairly constant relation to the body weight. 
The amount of blood in man averages -^ to - of the body weight. In 
other mammals the proportion of blood is also fairly constant, varying 
from ~ to -^5- of the body weight. In many of the lower vertebrates, the 
fishes for example, the relative quantity of blood is very much less. 

It is difficult to make an exact estimate of the quantity of blood in 
animals or in man though the blood volume in man is of great importance 
from the standpoint of disease. Measurements are constantly given 



for the number and distribution of the corpuscles and of the blood volume 
index. This data, to be of value, must be compared with the total pro- 
portionate amount of blood. A comparatively recent determination of 
this question was made by methods that are modern by Keith, Rowntree, 
and Geraghty. They injected a known quantity of a dye that is absorbed 
with difficulty, vital red. As soon as the dye was distributed, three 
minutes, they withdrew blood into powdered oxylate from the correspond- 
ing vein of the other arm, centrifuged quickly and compared the stained 
plasma obtained from the arm with a standard dilution of the dye, using 
the colorimetric method. Computation yielded the following facts. 
The total blood averaged 8.8 per cent., ~^ of the body weight. This is 
about 85 cubic centimeters per kilo. The plasma averaged about 50 
cubic centimeters per kilo. 

This quantity of blood is distributed in the different parts of the body, 
chiefly in the muscles, the liver, the heart, and larger blood vessels, as 
shown by the following figures determined on the rabbit by Ranke (from 
Vierordt) : 

Per cent. 

Spleen o . 23 

Brain and cord 1.24 

Kidney 1.63 

Skin 2.10 

Abdominal viscera 6.30 

Cartilage 8 . 24 

Heart, lungs, and large blood vessels 22.76 

Resting muscle 29 . 20 

Liver 29.30 

The normal blood volume varies somewhat with relation to the intake 
of food and drink. Relative body dessication would appear in extreme 
thirst or under conditions of unusual loss of water without increasing the 
intake, as in extreme perspiration, diarrheas, etc. 


The most characteristic property which the blood possesses is that of 
clotting or coagulating. This phenomenon may be observed under the most 
favorable conditions in blood which has been drawn into an open vessel. In 
about two or three minutes, at the ordinary temperature of the air, the surface 
of the fluid is seen to become semisolid or jelly-like, and this change takes 
place, in a minute or two afterward, at the sides of the vessel in which it is 
contained and then quickly extends throughout the entire mass. The time 
which is occupied in these changes is about eight or nine minutes. The 
solid mass is of exactly the same volume as the previously liquid blood, and 
adheres so closely to the sides of the containing vessel that if the latter be 
inverted none of its contents escape. The solid mass is the crassamentum 
or clot. If the clot be watched for a few minutes, drops of a light, straw- 
colored fluid, the serum, may be seen to make its appearance on the surface, 


and, as it becomes greater and greater in amount, to form a complete super- 
ficial stratum above the solid clot. At the same time the serum begins to 
transude at the ddes and at the under surface of the clot, which in the course 
of an hour or two floats in the liquid. The appearance of the serum is due 
to the fact that the clot contracts, thus squeezing the fluid out of its mass. 
The first drops of serum appear on the surface about eleven or twelve min- 
utes after the blood has been drawn; and the fluid continues to transude for 
from thirty-six to forty-eight hours. 

The clotting of blood is due to the development in the plasma of an in- 
soluble substance called fibrin. This fibrin forms threads or strands through 
the mass in every direction. The strands adhere to each other wherever 
they come in contact, thus forming a very dense tangle and meshwork which 
incloses within itself the blood-corpuscles. The clot when first formed, 
therefore, includes the whole of the blood in an apparently solid mass, but 
soon the fibrinous meshwork begins to contract and the serum is squeezed 
out. When a large part of the serum has been squeezed out the clot is found 
to be smaller, but firmer and harder, as it is now made up more largely of 
fibrin and blood corpuscles. Thus in coagulation there is a rearrangement 
of the constituents of the blood; liquid blood consisting of plasma and 
blood corpuscles, and clotted blood of serum and clot. These relations are 
roughly shown in the following diagram: 

Liquid blood. 

Plasma. Corpuscles. 

Serum. Fibrin. 


Clotted blood. 

The rapidity with which coagulation takes place varies greatly in different 
animals and at different times in the same animal. Where coagulation is 
very slow the red corpuscles, which are somewhat heavier than plasma, 
often have time to settle considerably before the fibrin is formed. If the 
blood is rapidly cooled to a temperature approaching o C. then the clot is 
very greatly delayed. Horse's blood is particularly favorable for demon- 
strating this point. In it clotting occurs so slowly that very often the red 
corpuscles will completely settle out, and when the* blood is again warmed 
and the clotting takes place there is a superficial stratum differing in appear- 
ance from the rest of the clot, having a grayish-yellow color. This is known 



as the bufy coat or crusta phlogistica. The buffy coat, produced in the man- 
ner just described, commonly contracts more than the rest of the clot, on 
account of the absence of colored corpuscles from its meshes. When the 
clot is allowed to stand, the white corpuscles which have escaped the clot 
by ameboid movement settle on its surface often in such numbers that they 
form a distinct superficial layer, grayish-white in appearance. 

That the clotting of blood is due to the gradual appearance in it of fibrin 
may be easily demonstrated, For example, if recently drawn blood be 
whipped with a bundle of twigs or wires, the fibrin may be withdrawn from 
the blood before it can entangle the blood corpuscles within its meshes. 
It adheres to the twigs in stringy threads relatively free from corpuscles. 
The blood from which the fibrin has been withdrawn no longer exhibits the 
power of spontaneous coagulability and it is now called defibrinated blood. 
Although these facts have long been known, the closely associated problem 
as to the exact manner in which fibrin is formed is by no means so simple. 

FlG. 107. Reticulum of Fibrin, from a Drop of Human Blood, after Treatment with 

Rosanilin. (Ranvier.) 

Fibrin is derived from the plasma. Pure plasma may be procured by 
delaying coagulation in blood by keeping it at a temperature slightly above 
freezing-point, until the colored corpuscles have subsided to the bottom of 
the containing vessel. The blood of the horse is specially suited for the 
purposes of this experiment. A portion of the colorless supernatant plasma, 
if decanted into another vessel and exposed to the ordinary temperature of 
the air, will coagulate, producing a clot similar in all respects to blood clot, 
except that it is colorless from the absence of red corpuscles. If some of 
the plasma be diluted with twice or three times its bulk of normal saline 
solution (0.9 per cent.), coagulation is delayed, and the stages of the gradual 
formation of fibrin in it may be conveniently watched. The viscidity which 
precedes the complete coagulation may be actually seen to be due to the 
formation of fibrils of fibrin first of all at the edge of the fluid-containing 



vessel, and then gradually extending throughout the mass. If a portion of 
plasma, diluted or not, be whipped with a bundle of twigs or wire during the 
process of clotting, the fibrin will be obtained as a stringy, insoluble mass, just 
in the same way as from the entire blood. The resulting fluid no longer 
retains its powei of spontaneous coagulability and is in fact now a typical 

Theories of Coagulation. It is evident that the blood plasma contains 
some substance or substances which take part in the formation of fibrin. 
By numerous investigations it has been found that the direct antecedent of 
the fibrin is the protein substance, fibrinogen. This fibrinogen exists in the 
blood plasma at all times, but is somewhat increased under certain condi- 
tions. The fibrinogen is reacted on by another substance known as thrombin. 
We shall not present the numerous theories which have been held concerning 
blood coagulation, many of which have been more or less disproven, but shall 
try to present the condensed statement of the present explanations of this 

Blood Tissue Cell 

Neutral Salts Fibrinogen Calcium Salts 

(for dissolving 


Thrombok ina se 

Morawitz' Schema of Coagulation. 

intricate phenomenon. One may start from the statement that the fibrinogen 
of the plasma when acted upon by the thrombin, also of the plasma, produces an 
insoluble substance, fibrin. The chief interest centers around the origin and 
character of ihefirbinogen, the origin and nature of the thrombin, and the con- 
ditions which influence its activity. 

The fibrinogen is present in blood plasma of the circulating blood of the 
body at all times. It can be separated from plasma by various chemical 
means, and when purified can be made to form fibrin under proper conditions. 
All observers are agreed that this protein is the immediate precursor of the 
insoluble fibrin. Its origin in the blood has been traced by Matthews to the 
disintegration of the white blood corpuscles. 

The thrombin is the substance which reacts on the fibrinogen in the 


processes of fibrin formation. It does not exist in the living blood 
vessels, or at least is present only in minute quantities, but makes its 
appearance immediately the blood is drawn. 

The sources of these substances and the part taken by each in the 
process of coagulation are given by Morawitz. If blood be drawn, centri- 
fugalized, and the leucocytes and blood plates separated from the plasma 
and suspended in water, their solution will cause the formation of fibrin 
from fibrinogen in the presence of calcium. The leucocytes and platelets 
are, therefore, the source of thrombin. The thrombin can be isolated in a 
stable condition, and when its solutions are added to fibrinogen solutions 
fibrin is formed. By Morawitz' view the appearance of thrombin in the 
blood is due to the interaction of at least three antecedent substances. 
These are, i, prothrombin (thrombogen), 2, calcium, and 3, thrombo- 
kinase (cytozym). If the blood is drawn from vessels with due pre- 
cautions, i.e., not to allow it to come in contact with the cut vessel or other 
tissue, clotting is very much delayed. The plasma if separated by the 
centrifuge will remain unclotted for a long time as shown by Howell for 
the terrapin's plasma. This plasma will quickly clot at any time if a few 
drops of tissue extract in salt solution be added. When blood is drawn over 
the lacerated tissue of a wound it clots more quickly. These observations 
have led to the assumption of an activating substance or kinase to which 
the name thrombokinase has been given by Morawitz. It is assumed to 
have its origin in tissue cells and in the cells of the blood, especially the 

If precautions are taken to draw the blood in such a manner as to re- 
move the calcium from the plasma, no clot is formed. The calcium which 
exists in solution in the plasma to the extent of 0.026 per cent, (measured 
as calcium chloride) can be removed by precipitation with oxalate solution 
or by the action of fluorides or citrates which bind the calcium so that it is 
no longer available to the prothrombin. Such plasma contains fibrinogen, 
prothrombin, and thrombokinase, and whenever calcium chloride is added 
to excess, coagulation takes place. 

L. J. Rettger has recently made a re-examination of the conditions for the 
clotting of blood. He questions the interpretation of the facts on the basis of 
which the assumption of a kinase is made. He says: 

"Terrapin's blood taken carefully through an oiled cannula and put into 
a perfectly clean beaker will remain fluid for days. The blood may be cen- 
trifuged, and the clear supernatant plasma is then equally or more resistant 
to spontaneous clotting. If, however, tissue extracts or pieces of tissue be 
added, the coagulation is pronounced and immediate. The most apparent 
explanation is that a thrombin or coagulin or kinase is present in the extract. 
But this blood or plasma can be made to clot equally well and equally rapidly 
in ways which preclude the presence of such a definite agent. If, for instance, 


dust particles, loose sweepings, or linty shreds be added, the coagulation is 
equally prompt and in a number of experiments was more rapid than with tis- 
sue extract." "The bird's blood or plasma clots with practically the same 
rapidity and firmness if dust particles are generously added. Bits of down 
or feathers introduced bring about a speedy clotting. Surely there can be 
no question of a 'kinase' in these instances." "The existence of 'kinase' 
or 'coagulins' in the various tissues is improbable. Using carefully pre- 
pared fibrinogen solutions, extracts of tissues, irrigated to remove every 
trace of thrombin-containing blood, cause no clotting. When the addition 
of such extracts produces coagulation in bloods of bird or reptile, similar 
results can be secured by the addition of substances, such as dust, lint, 
shreds, etc., which preclude the presence of definite coagulating agents. 
These results render very probable the assumption that in such plasmas all 
the factors of coagulation are in reality present, and the addition of tissue 
extract or other foreign substance brings into the mixture nothing that can 
be regarded as a coagulin or as a kinase." 

Howell has been studying the phenomena of coagulation for- a number of 
years. On the basis of his work he makes a somewhat different interpreta- 
tion of the facts on which the theory of Morawitz is founded. By Howell's 
view, "Circulating blood contains normally all the necessary fibrin factors, 
namely, fibrinogen, prothrombin, and calcium. These substances are pre- 
vented from reacting, and the normal fluidity of the blood is maintained, by 
the fact that antithrombin is also present, and this substance prevents the 
calcium from activating the prothrombin to thrombin. In shed blood the 
restraining effect of the antithrombin is neutralized by the action of a sub- 
stance (thromboplastin) , furnished by the tissue elements. In the mammalia 
the thromboplastin is derived, in the first place, from the elements of the 
blood itself (blood platelets). In the lower vertebrates the supply of this 
material, in normal clotting, comes from the external tissues." Howell's 
thromboplastin and Morawitz' thrombokinase are probably one and the 
same substance, it being an enzyme by Morawitz' view, a property denied 
by Howell and by Rettger. 

Quite recently Howell has thrown light on the nature of his thromboplastic 
substance. He finds that the lipoid, kephalin, present in many tissues of the 
body possesses the power of neutralizing antithrombin and is comparable, in 
relation to blood clotting, to the action of thromboplastin. Lecithin does not 
possess this property. 

One may restate Morawitz' view in a word as follows: The coagulation of 
the blood takes place because of the formation of fibrin from fibrinogen by 
the action of thrombin. The fibrinogen is constantly present in the plasma. 
The thrombin is formed by the interaction of three substances, prothrombin, 
calcium, and thrombokinase. The prothrombin arises chiefly from the dis- 
integration of the blood platelets and leucocytes when the blood leaves the 


blood vessels. The calcium is present in the blood plasma at all times. 
The thrombokinase originates in tissue cells of the blood and of the organs of 
the body in general. 

Rettger's view is best given in his own words: " On the basis of the work 
here presented it is not necessary to assume the existence of a kinase in explain- 
ing the clotting of shed blood. The prothrombin formed from the platelets 
and leucocytes by secretion or by processes of disintegration is activated to 
thrombin by the calcium salts present, and the thrombin so formed combines 
in quantitative fashion with the fibrinogen to form fibrin." 

Howell's demonstration of antithrombin offers a new factor in the 
problem of blood clotting. For example, the hastening influence of keph- 
alin on blood clotting is probably due to its action on antithrombin, 
rather than on either of the other clotting complexes. 

The Coagulation Time of Blood. The rapidity with which blood co- 
agulates varies greatly in different animals. In the majority of mammals 
the coagulation time varies from 2.5 to 5 minutes. In man this time is 
about 3 to 3:5 minutes in normal blood. In recent experiments by Cannon 
and Mendenhall, on the coagulation time of the blood from the dog and 
cat, determined by a new and mechanically accurate method, the normal 
coagulation time is given as from 3 . 5 to 4. 5 minutes. This coagulation time 
however varies under different conditions of the animal, especially under 
conditions which affect the activities of the glands, in particular the epine- 
phros. Stimulation of this gland either directly by stimulation of the 
splanchnic nerves, or indirectly through conditions that arouse fear, etc., 
leads to a sharp diminution in the coagulation time of the blood. This 
decrease in some instances is well within i minute, less than ^ minute in 
their experiment 3, which was an experiment after emotional excitement. 
The coagulation time is retarded by the elimination of the circulation of 
the intestine and of the liver, also by nephrectomy. 

Conditions Affecting Coagulation. From the preceding discussion 
it is evident that the rapidity of the coagulation of the blood will be 
influenced by anything that will influence the formation of the fibrin 
factors or their interaction. The most important influences are the 

Condition of the Blood. The blood varies greatly through a wide range 
in its ability to form fibrin. This depends upon the interaction of those 
tissues that produce the fibrin factors. An efficient circulation through the 
abdominal viscera is necessary to maintain the clotting properties of the 
blood. The rapidity of clotting is increased following the process of 
digestion. It is also increased (Cannon) by the injection of epinephrin or 
by the stimulation of the splanchnic nerves which increase the output of 
epinephrin by the suprarenal bodies. (See Influence of the Ductless 
Glands, page 482). If those glands be removed, the time of blood clotting 



increases. The exclusion of the abdominal circulation tends to increase 
the time of blood clotting, and if the liver circulation be eliminated, the 
influence of epinephrin is lost. 

Hemorrhage increases the rapidity of coagulation, apparently by stimu- 
lating the production of the fibrin factors. 

FIG. 1 08. Diagram of the Graphic Coagulometer. C, 
In a cannula of convenient working size, 2 mm. internal 
diameter, and 2 cm. long, which when filled with a sample 
of fresh circulating blood is quickly plugged with wax and 
connected by a short rubber tube with a longer glass tube 
held in the support U. The whole is then immersed in 
a beaker of water at constant temperature (not shown in 
the figure). D, A copper wire of standard weight hanging 
over the lever, the looped end is immersed in the sample of 
blood, C. W, Counterpoising weight for the lever which 
rotates on the axis A. S, Lever support. R X -R 2 , Short L-shaped arm which when 
moved from P 1 to P 2 releases the lever at R 1 . To use the instrument, draw the 
sample of blood at a signal, insert it in the apparatus, and at regular intervals release 
the lever by moving the arm R 2 . If the blood is fluid, the counterpoising lever will 
make a vertical stroke through its free range. If threads of fibrin have formed, these 
counteract the movement of the lever. E, Time signal. From Cannon. 

Condition of the Blood-vessel Walls. Intravascular clotting often takes 
place upon injury of the endothelial lining of the blood vessels, either from 
the liberation of thrombokinase in quantity too great for elimination by the 
healthy portion of the wall (Morawitz), or by the disturbance of the equi- 
librium of the forces which prevent the interaction of the fibrin factors 
present in the blood (Rettger). The healthy endothelium no doubt is an im- 
portant factor in controlling the relative amounts of the fibrin factors that 
must be constantly forming. The open wounds and lacerations of tissue 
that accompany the loss of blood by accident are the very conditions most 
favorable to clotting, since large amounts of tissue extract are set free under 
these conditions. 

Temperature. Cold retards coagulation. Gentle warmth, 40 C., has- 
tens, but a temperature above 56 C. destroys clotting, since that temperature 
heat-coagulates the fibrinogen. 

Contact "with Foreign Bodies. Such contact hastens clotting. This is 
due to the influence of such bodies in hastening the formation of fibrin 
factors, especially the substances that arise from the disintegration of 

Neutral Salts. The additon of neutral salts in the proportion of 2 or 3 
per cent, and upward delays coagulation. When added in large propor- 
tions, most of these saline substances prevent coagulation altogether. 
Coagulation, however, ensues on dilution with water. The time during 
which salted blood can be thus preserved in a liquid state, and coagulated 


by the addition of water, is quite indefinite, if measures be taken to pre- 
vent putrefaction. 

Oxalates and Fluorides. Oxalates to the extent of o.i per cent, con- 
centration prevent clotting by the removal of calcium, one of the factors 
in the formation of thrombin. Once thrombin is formed, clotting will 
take place in the absence of soluble calcium. This is proven by the fact 
that solutions of pure fibrinogen and thrombin form fibrin clots. 

Flourides, on the other hand, not only precipitate soluble calcium but 
fix the blood platelets from which the prothrombin is formed. 

Peptone. The injection of commercial peptone (a mixture of proteoses 
and peptones) in the blood vessels of an animal to the extent of o . 5 gram 
of peptone per kilo weight of the body of the animal will deprive the blood 
of the power of coagulation. If a smaller quantity be injected the coagula- 
tion of the blood will be delayed. If peptone blood is drawn and centri- 
fuged, the plasma obtained is called peptone plasma. Howell has shown that 
peptone contains antithrombin in a relatively large quantity. The increase 
of antithrombin acts to restrain the reaction of prothrombin in the formation 
of thrombin. Peptone plasma in the blood vessels of the animal gradually 
regains the power to coagulate. When blood is drawn into a physiological 
salt solution of proteose-peptone clotting occurs. 


The corpuscles floating in the fluid plasma of the blood, when separated 
by a centrifugal machine are found to make up 45 to 50 per cent, of the total 
mass of the blood. These corpuscles, or formed elements, are of three 
varieties, the red corpuscles or erythrocytes, the white corpuscles leucocytes, 
and the blood platelets which have been called thrombocytes. 

Red Corpuscles or Erythrocytes. Human red blood corpuscles are 
circular, biconcave discs with rounded edges, from j/j. to 8/* in diameter, 
and about 2/z in thickness. When viewed singly they appear of a pale 
yellowish tinge; the deep red color which they give to the blood being ob- 
servable in them only when they are seen en masse. They are composed 
of a colorless, structureless, and transparent filmy framework or stroma, 
infiltrated in all parts by the red coloring matter, the hemoglobin. The 
stroma is tough and elastic, so that as the corpuscles circulate they admit 
of elongation and other changes of form in adaption to the vessels, yet 
recover their natural shape as soon as they escape from compression. 

Number and Character of the Red Corpuscles. The normal number of 
red blood-cells in a cubic millimeter of human blood was estimated by 
Welcker, in 1854, to be 5,000,000 in men and 4,500,000 in women. Num- 
erous recent observations, however, have shown that these estimates are a 
little low, especially in men, and the average number has been placed by 
different authorities at various points between 5,000,000 and 5,500,000. 
Still the original numbers as given by Welcker are accepted at the present 



day as being sufficiently accurate for ordinary purposes. It has been also 
shown that there are many distinct physiological variations in the number, 
depending on the time of day, digestion, sex, etc. The number of red cells 
usually diminishes in the course of each day, while the leucocytes increase 
in number. It has been suggested that this is due to the influence of 
digestion and of exercise. 

It has generally been found that within half an hour or an hour after a 
full meal the number of red cells begins to diminish, and that this keeps up 
for from two to four hours, when it is followed by a gradual rise to the normal. 
The usual fall is 250,000 to 750,000 per cubic millimeter. These results 
are most marked after a largely fluid meal, and are probably due to dilution 
of the blood as a result of the absorption of fluids. In animals the number 
of red cells is increased by fasting, but in man the results are variable, some 

FIG. 109. 

FIG. no. 
The rounded or uncolored corpuscles are 

FIG. 109. Red Corpuscles in Rouleaux, 

FIG. no. Corpuscles of the Frog. The central mass consists of nucleated colored 
corpuscles. The other corpuscles are two varieties of the colorless form. 

authorities claiming an increase and others a decrease. In childhood there 
is no difference between the sexes in the number of red cells per cubic milli- 
meter, but after menstruation is established a relative anemia develops in 
women. Welcker's original estimate placed the difference at 500,000 per 
cubic millimeter, and these figures have been generally accepted, though 
Leichtenstein asserts that the difference is 1,000,000. 

Menstruation in healthy subjects has practically no effect, as not more 
than 100-200 cubic centimeters of blood are lost normally in the course of 
several days. Under such circumstances the normal diminution of red cells 
per cubic millimeter is probably less than 150,000, though Sfameni has placed 
the loss at about 225,000. The leucocytes are slightly increased during 
menstruation. It is now the general opinion that pregnancy has little or no 
effect on the number of red cells, and that any anemia must be due to abnormal 
conditions. Post-partum anemia should not last longer than two weeks. 



The red corpuscles are not all alike. In almost every specimen of blood a 
certain number of corpuscles smaller than the rest may be observed. They 
are termed microcytes, or hematoblasts, and are probably immature corpuscles. 

A peculiar property of the red corpuscles, which is exaggerated in in- 
flammatory blood, may be here again noticed, i. e,, their great tendency to 

FIG. in. Illustration exhibiting the typical characters of the red blood-cells in the 
main Divisions of the Vertebrata. The fractions are those of an inch, and represent the 
average diameter. In the case of the oval cells, only the long diameter is here given. It is 
remarkable, that although the size of the red blood-cells varies so much in the different 
classes of the vertebrate kingdom, that of the white corpuscles remains comparatively 
uniform, and thus they are, in some animals, much greater, in others much less, than the 
red corpuscles existing side by side with them. Modified from Gulliver. 

adhere together in rolls or columns (rouleaux), like piles of coins. These 
rolls quickly fasten together by their ends, and cluster; so that, when the 
blood is spread out thinly on a glass, they form a kind of irregular network, 
with crowds of corpuscles at the several points corresponding with the knots 
of the net, figure 109. Hence the clot formed in such a thin layer of blood 
looks mottled with blotches of pink upon a white ground. 



The red corpuscles are constantly undergoing disintegration in different 
parts of the circulatory system, particularly in the spleen. The liberated 
hemoglobin contributes to the formation of the bile pigments in the liver. 

Development of the Red Blood Corpuscles. The first formed 
blood corpuscles of the human embryo differ much in their general characters 
from those which belong to the later periods of intra-uterine, and to all 
periods of extra-uterine life. Their manner of origin is at first very simple. 

Surrounding the early embryo is a circular area, called the vascular area 
in which the first rudiments of the blood vessels and blood corpuscles are 
developed. Here the nucleated embryonal cells of the mesoblast, from 
which the blood vessels and corpuscles are to be formed, send out processes 
in various directions, 
and these, joining to- 
gether, form an irregu- 
lar mesh-work. The 
nuclei increase in num- 
ber, and collect chiefly 
in the larger masses of 
protoplasm, but partly 
also in the processes. 
It appears that hemo- 
globin then makes its 
appearance in certain 
of these nucleated em- FIG. 112. Part of the Network of Developing Blood 

brvonal cells which Vessels in the Vascular Area of a Guinea-pig. Showing blood 
corpuscles becoming free in an enlarged and hollowed-out 

thus become the earliest part of the network and processes of protoplasm. (E. A. 
red blood corpuscles. Schafer.) 

The protoplasm of the cells and their branched network in which these, 
corpuscles lie then become hollowed out into a system of canals enclosing 
fluid in which the red nucleated corpuscles float. The corpuscles at first 
are from about IOJJL to i6/< in diameter, mostly spherical, and with granular 
contents, and a well-marked nucleus. Their nuclei, which are about 5^ 
in diameter, are central, circular, very little prominent on the surfaces of 
the corpuscles, and apparently slightly granular. 

The corpuscles then strongly resemble the colorless corpuscles of the 
fully developed blood but for their color. They are capable of ameboid 
movement and multiply by division. 

When, in the progress of embryonic development, the liver is formed, 
the multiplication of blood-cells in the whole mass of blood ceases, and new 
blood-cells are produced by this organ, and also by the spleen. These are 
at first colorless and nucleated, but afterward acquire the ordinary blood 
tinge, and resemble very much those of the first set. They also multiply by 
division. The bone marrow also begins to form red corpuscles, though at 


first in small amounts only. This function develops rapidly, however, so 
that at birth the marrow represents the chief seat of production of the red 
cells. Nevertheless, nucleated red cells are usually found at birth, sometimes 
in considerable quantities in the liver and in the spleen. Non-nucleated 
red cells begin to appear soon after the first month of fetal life, and gradually 
increase so that at the fourth month they form one-fourth of the whole amount 
of colored corpuscles. At the end of fetal life they almost completely re- 
place the nucleated cells. In late fetal life the red cells are formed in almost 
the same way as in extra-uterine life. 

FIG. 113. FIG. 114. 

FIG. 113. Multiplication of the Nucleated Red Corpuscles. Marrow of young 
kitten after bleeding, showing above karyokinetic division of erythroblast, and below the 
formation of mature from immature erythrocytes. (Howell.) 

FIG. 114. Shows the Way in which the Nucleus Escapes from the Nucleated Red 
Corpuscles, i, 2, 3, 4, represent different stages of the extrusion noticed upon the living 
corpuscles, a, Specimen from the circulating blood of an adult cat, bled four times; b, 
specimen from the circulating blood of a kitten forty days old, bled twice; c, specimens 
from the blood of a fetal cat, 9 cm. long. Others from the marrow of an adult cat, two of 
the figures showing the granules present in the corpuscles, which have been interpreted 
erroneously as a sign of the disintegration of the nucleus. (Howell.) 

Various theories have prevailed as to the mode of origin of the non- 
nucleated colored corpuscles. For a time it was thought that they were of 
endoglobular origin, and merely fragments of some original cell, being pro- 
duced by subdivision of the cell body itself. This theory easily accounted 
for the absence of the nuclei, but it has not been supported by recent investi- 
gations. At present it is the general belief that the non-nucleated cells, or 
erythrocytes, are derived from nucleated cells by a process of mitotic division, 
and further that their nuclei gradually shrink or fade and are then extruded. 
The use of some of the more recent stains seems to prove that there are traces 
of nuclear material in the non-nucleated corpuscles. 

After infancy and early childhood the origin of erythrocytes is practically 
limited to the red marrow of the bones. The mother cells, or erythroblasts, 
are constantly forming and setting free erythrocytes, the rate varying greatly 
at different periods. 


The Colorless Corpuscles or Leucocytes. In human blood the white 
corpuscles, leucocytes, are nearly spherical masses of granular protoplasm 
without cell wall. In all cases one or more nuclei exist in each corpuscle. 
The corpuscles vary considerably in size, but average IO/JL in diameter. 

The number of leucocytes in a cubic millimeter of blood is estimated 
at 7,500 to 8,000. The proportion of white corpuscles to red, therefore, is 
about one of the former to 700 of the latter. This proportion is not very 
constant in health and great variations occur under the influence of disease 

FIG. 115. Colored Nucleated Corpuscles, from the Red Marrow of the Guinea-pig. 

(E. A. Schafer.) 

especially in certain infectious diseases in which the number of white cor- 
puscles is markedly increased. 

After a full meal the white cells in a healthy adult are increased in number 
about one-third, the increase beginning within an hour, attaining a maxi- 
mum in three or four hours, and then gradually falling to normal. This 
process is frequently modified by the character of the food, the greatest 
increase occurring with an exclusively meat diet, while a purely vegetarian 
diet has usually no effect. The increase is also more marked in children, 
and especially in infants. The essential factor is probably the absorption 
of albuminous matter in considerable quantities. This causes proliferation 
of leucocytes in the lymphoid tissue of the gastro-intestinal tract. 

In pregnancy there is often a moderate increase in the number of white 
cells during the later months. This does not begin until after the third 
month, and is most marked and constant in primiparae. After parturition 
the leucocytes gradually diminish under normal conditions, and usually 
reach the normal within a fortnight. The essential factor is probably the 
general stimulation in the maternal organism. It is well established that the 
white cells are very numerous in the new-born, though different observers 
have made very conflicting estimates. Still all agree that there is a very 
rapid decrease in their numbers during the first few days, and that this is 
followed by a less marked increase, which continues for many months. 
According to Rieder there are at birth from 14,200 to 27,400 per cubic milli- 
meter, and after the fourth day from 12,400 to 14,800. 

The colorless corpuscles present a great diversity of form. There are 
certain constant types found in fairly definite proportions in normal 
blood, but in pathological bloods a long series of variants have been 
described and figured by such authors as Wood, Webster, and Simon. In 
histological and clinical examination the white corpuscles are classified 


according to their size, structure, and staining reaction. Some of these 
cells are mononuclear, others polynuclear and many charged with special 
types of granules that take now basic, now acid dyes, presumably accord- 
ing to their clinical composition. The following varieties may be listed 
for normal adult blood. 

1. Small mononuclear leucocytes, 22-25. 

2. Large mononuclear leucocytes, 1-2. 

3. Polynuclear neutrophilic leucocytes, 65-75. 

4. Polynuclear eosinophilic leucocytes, 1-4. 

5. Polynuclear basophilic leucocytes, mast cells, 0.2 to 0.5. 

The small mononuclear leucocytes, or lymphocytes, are about the size 
of or smaller than the red corpuscles, a single nucleus with very little 
nongranular protoplasm, staining deeply with methyline blue with a 
lighter staining nucleus, 22 to 25 per cent. 

The large mononuclear leucocytes are double the size of the small leuco- 
cytes or even larger. They have a single nucleus about the size of the 
preceding type but a much larger relative development of protoplasm. 
Their cytoplasm is not granular and they are weakly basophilic. These 
cells like the small leucocytes arise in the lymphoid tissue. 

The polynuclear neutrophilic leucocytes are about the size of a red blood 
corpuscle and are granular in appearance. The nuclei take basic dyes. 
The cytoplasm is slightly acidic but the granules imbedded in it are baso- 
philic. These leucocytes constitute from 65 to 75 per cent, of the total 
number of white corpuscles. This class is most actively phagocytic and 
is increased in number in response to most infections. 

The polynuclear eosinophilic leucocytes. The cells of this type are the 
largest cells of the white corpuscle group. Their cytoplasm is crowded with 
granules which stain deeply with eosin and other acid dyes. From this 
characteristic they get their name. The eosinophiles constitute i to 4 
per cent, of the total. They are extremely motile and phagocytic and are 
very greatly increased in number in certain diseases. 

The mast cells are much fewer in number except in certain particular 
diseases. They have a polymorphic nucleus characteristic in appearance. 
They take basic dyes with difficulty. These cells are also granular. The 
granules do not take eosin but are basic in type. They vary in size, being 
rather larger than eosinophilic granules. In normal blood one mast cell 
occurs in from 200 to 250 leucocytes. 

The relative number of leucocytes varies in children as compared with 
normal adults. The small mononuclear lymphocytes are practically 
double the adult number and the polymorphonuclears about half the 
number in the adult. The eosinophiles are also more frequent though 
still relatively rare. 



FIG. 116 (a) Red blood corpuscle for comparison; (b) Small lymphocyte; (c) 
Large lymphocyte (myelocyte); (d) Fine and (e) coarse eosinophiles; (/) Basophile. 
(F. C. Busch.) 

Ameboid Movement and Phagocytic Action of Leucocytes. The remark- 
able property of the colorless corpuscles of spontaneously changing their 
shape was first demonstrated by 
Wharton Jones in the blood of the skate. 
If a drop of blood be examined with 
a high power of the microscope, under 
conditions by which loss of moisture is 
prevented, and at the same time the 
temperature is maintained at about that 
of the body, 37 C., the colorless corpus- 
cles will be observed slowly to alter 
their shapes, and to send out processes 
at various parts of their circumference. 
The ameboid movement which can be 

demonstrated in human colorless blood FlG Il8 ._ Blood Plates> showing 
Corpuscles can be most conveniently chromatic centers regarded by some as 
studied in the newt's blood. Processes 
are sent out from the corpuscle. These 
may be withdrawn, but more often the protoplasm of the whole corpuscle 
flows gradually forward to the position occupied by the process, thus the 
corpuscle changes its position. The change of position of the corpuscle 
can also take place by a flowing movement of the whole mass, and in 
this case the locomotion is comparatively rapid. The activity both in 
the processes of change of shape and also of change in position is much 
more marked in some corpuscles than in others. Klein states that in the 



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newt's blood the changes are especially noticeable in a variety of 
colorless corpuscle, which consists of a mass of finely granular protoplasm 
with jagged outline and contains three or four nuclei, or in large irregular 
masses of protoplasm containing from five to twenty nuclei. 

The blood leucocytes are the phagocytes of the body. By means 
of their ameboid movements they surround or engulf foreign bodies 
including bacteria. These they digest, therefore destroy. It is through 
the activity of the leucocytes that the body gains its relative immunity, 
since these cells are able to overcome to a certain extent bacterial invasion. 
The blood largely depends on the polymorphonuclear leucocytes for 
phagocytosis, hence these cells are found to be increased in number under 
the stimulus of infectious processes. The relative numbers of leucocytes 
in clinical blood counts have their value in part in this fact. However, in 
clinical bloods many pathological types appear which are of special 

The Blood Platelets or Thrombocytes. A third variety of corpuscle 
found in the blood is known as the blood platelets. They are circular or 
elliptical in shape, of nearly homogeneous structure, and vary in size from 
0.5 to 5/-1/A. Hence they are smaller than the red corpuscles. They vary 
in number from 5,000 to 45,000 per cubic millimeter and are preserved 
by drawing fresh blood directly into Hayem's or other preserving fluid. 
When fresh blood is drawn the blood platelets, coming in contact with 
foreign bodies, rapidly disintegrate and give rise to one of the antecedents 
of blood plasma concerned in clotting, prothrombin, p. 121. 


The chemical composition of the blood as a whole may be presented 
by consideration of the constituents of the plasma and of the corpuscles. 
The available blood analyses have dealt with whole blood, with either 
plasma or serum and with whole corpuscles, although separate analyses 
of red and white corpuscles have been made. 

The classical analyses in the literature that have become the reliance 
for teaching purposes are those of Schmidt for the blood of man and of 
Abderhalden for dog's and horse's blood. These analyses are quoted in 
tabular form below. 


One Thousand Grammes of Blood. 

Blood- Corpuscles 513 . 02 

Water 349 -69 

Substances not vaporizing at 1 20 163 . 33 

Hematin 7 -7 (including 0.512 iron) 

Blood casein, etc 151 .89 

Inorganic constituents 3-74 (excluding iron) 



Chlorine 0.898 

Sulphuric acid 0.031 

Phosphoric acid o . 695 

Potassium i . 586 

Sodium 0.241 

Phosphate of lime o . 048 

Phosphate of magnesium 0-031 

Oxygen 0.206 

Blood Plasma 486 . 89 

Water 439 . 02 

Substances not vaporizing at 1 20 47 . 96 


Protein, etc 

Inorganic constituents 



Phosphoric acid 



Phosphate of lime 

Phosphate of magnesium .... 

Specific Gravity = 1.0599. 

Chloride of potassium . . . 
Sulphate of potassium . . . 
Phosphate of potassium. . 
Phosphate of sodium .... 


Phosphate of lime 

Phosphate of magnesium. 

Total. . 


1 . 202 

o . 03 1 





Sulphate of potassium 
Chloride of potassium 
Chloride of sodium 
Phosphate of sodium 

. . . . 0.137 
. . . . 0.175 

.... 2. 701 


o 14? 

Phosphate of lime 

.... o. 145 

o. 106 

O. 221 

Phosphate of magnesium 

.... o . i 06 



The Composition of Plasma. The plasma is the liquid part of the 
blood in which the corpuscles float. It differs from the serum only in that 
the fibrin factors have been removed during the process of clotting. To 
all intents and purposes the chemistry of the plasma and serum are iden- 
tical. Plasma may be freed from the corpuscles by the centrifugal 
machine in the interval before clotting forms. However, it is customary 
to delay clotting by means enumerated below. 

Cooled Plasma. If blood is drawn directly into a chilled vessel and 
kept at a temperature of about o C., or only two or three degrees higher, the 
corpuscles will settle out, leaving a clear supernatant plasma. This plasma 
will clot promptly on raising the temperature. This method yields a 
pure plasma for isolation of fibrinogen and for quantitative analysis. 

Salted Plasma. Blood will not clot if it is mixed with sodium sulphate 
or magnesium sulphate in adequate proportion, one part to twelve parts 
of blood of the former, and one part to six parts of blood of the latter. 
Salted plasma obtained by this method will coagulate on dilution. 

Oxalated Plasma. In experimental work it is customary to prevent 
blood clotting by receiving it into an oxalate solution or over a powder of 
an oxalate salt. It is necessary that the blood contain at least one tenth 
per cent, of oxalate. The oxalate removes the soluble calcium salts before 
the prothrombin is converted into thrombin. Oxalated plasma will not 


clot until a calcium salt is added. The oxalate does not interfere with gas 
absorption and gas determination tests. 

Hirudin Plasma. Leach extract contains an anticoagulant which 
prevents clotting of blood. Such blood clots readily on adding serum or 
other solution containing thrombokinase which neutralizes the hirudin 
effect as it does the antithrombin when blood is drawn. 

Peptone Plasma. Peptone solution injected directly into the blood 
stream renders the blood non-coaguable when it is afterward drawn. 
Peptone does not prevent blood from clotting when mixed in vitro. How- 
ever, when blood serum or a pure solution of fibrin ferment is added, both of 
which neutralize the antithrombin, then peptone plasma will form a clot. 

Water of Blood Plasma. The water of the plasma varies in amount 
through a wide range. During absorption of food and drink the water 
increases temporarily in the blood, though at this time it is flowing into 
the tissues and being more rapidly excreted by the kidneys. In a few 
minutes, say 15 or 20, after a glass of water the blood constituents will be 
diluted and the red corpuscles demonstrably swollen. This condition 
is quickly equalized. On the other hand the rapid loss of water in evapor- 
ation of sweat following vigorous exercise quickly leads to loss of water 
from and concentration of the plasma. These variations occur around an 
average content of 90 per cent, of plasma water. 

Proteins. The chief proteins of plasma are serum albumin, serum 
globulin, and fibrinogen, a total of from 6 to 8 per cent, of the plasma. 
Fibrinogen is the part of plasma that is converted into fibrin when blood 
clots. It is a globulin. Fibrinogen is precipitated from plasma by half 
saturation with sodium chloride and along with globulin by full saturation 
with sodium chloride or magnesium sulphate. It is soluble in dilute salt 
solutions but not soluble in water. 

Serum globulin or paraglobulin is completely precipitated by saturation 
by magnesium sulphate, incompletely by sodium chloride, and coagulates 
at a temperature of 75 C. It is likewise soluble in dilute salt solutions, 
but insoluble in water. It is present in plasma in from 3.5 to 4 per cent., 
but varies greatly. 

Serum albumin is the protein which predominates in human plasma. 
It is readily obtained in crystalline form ; is soluble in saturated magnesium 
sulphate and sodium chloride solutions, but insoluble in saturated ammon- 
ium sulphate solutions. It coagulates in neutral or acid solutions at from 

73 to 75 C. 

Extractives. The extractives are the nitrogen-containing substances, 
such as urea, uric acid, creatin, creatinin, etc., and the non-nitrogenous 
glycogen, dextrose, cholesterin, etc., a total of 0.5 to 0.6 per cent. The 
dextrose content amounts to from o.i to 0.15 per cent. 

Among the extractives must be classed the various hydrolytic ferments 
such as the diastatic ferments that react with the carbohydrates of the 


blood, liver, etc.; the lipolytic or fat-splitting ferments, and the proteolytic 
ferments. From their property of producing not only hydrolytic cleavage 
but the reverse reactions of synthesis these ferments hold one of the most 
significant positions among the plasma constituents. 

Inorganic Substances. The total inorganic salts of human plasma 
amount to from 0.80 to 0.89 per cent. By the recent titration method of 
Cramer, the sodium ran 323 to 344 milligrams per 100 cubic centimeters 
of serum. The chief salt is sodium chloride which constitutes over half 
the total and contributes largely to the osmotic pressure of the blood. 
Curiously enough only a minimal quantity of potassium salt is present in 
the plasma, from 18 to 21 milligrams in a hundred grams. The potassium 
exists as sulphate and basic phosphate. The calcium is very constant in 
normal serum, from 9.3 to 9.9 milligrams in a hundred cubic centimeters 
of serum. It is probably in the blood as a phosphate. The calcium con- 
tent varies greatly in disease, is depressed in parathyroid tetany. 

The Serum. The serum is the liquid part of the blood or of the plasma 
which remains after the fibrin has been formed and removed. It is a 
transparent yellowish fluid with a specific gravity of 1025 to 1032. Serum 
is ordinarily obtained free from blood corpuscles by whipping the blood, 
that is removing the fibrin as fast as it forms and then sedimenting the 
corpuscles in the centrifugal machine. It may be obtained by allowing 
blood to clot in a test tube or beaker and then stand in the cold. The 
clot contracts, squeezing out the clear yellowish straw-colored serum. In 
quantitative chemical analysis the serum is essentially of the same compo- 
sition as plasma, in fact serum is usually taken for such quantitative work. 
It differs from plasma only in the loss of the fibrin or the fibrin factors 
which go to form fibrin. It is usually rich in thrombokinase or fibrin 
ferments. The percentages given above for the salts of plasma were 
actually determined on serum. 

The Composition of the White Corpuscles. The white corpuscles 
are comparatively undifferentiated cellular elements, hence possess the 
chemical composition of protoplasm. Lillienfeld has made an analysis 
of the leucocytes of thymus gland from the calf, which contain 11.49 P er 
cent, of solids, as follows: 

In 100 Parts of Dry Substance of White Corpuscles of Calf. 

Per cent. 

Protein 1.76 

Leuconuclein 68 . 78 

Histon 8 . 76 

Lecithin 7.51 

Fat 4.02 

Cholesterin 4 .40 

Glycogen o . 80 




Most noteworthy substances in this table are the nuclein and histon, 
first isolated by Kossel and Lillienfeld as nucleohiston. Besides the 
substances in the table, the white corpuscles contain salts of potassium, 
sodium, calcium, and magnesium, with potassium phosphate present in 
greatest amount. 

The Composition of the Red Corpuscles. Analysis of moist blood 
corpuscles shows the following results: 

Water 68.8 per cent. 

Organic 30-388 

Mineral.. 0.812 f 3I ' 2 

Of the solids the most important is the respiratory pigment, hemoglobin, 
the substance to which the blood owes its color. It constitutes, as will be 
seen from the appended table, more than 90 per cent, of the organic matter 
of the corpuscles. Besides hemoglobin the corpuscles contain protein and 
fatty matters, the former chiefly consisting of globulins, and the latter of 
cholesterol and lecithin. 

In 100 parts of organic matter are found: 

Hemoglobin 90 . 54 per cent. 

Proteins 8.67 per cent. 

Fats o . 79 per cent. 


The inorganic salts of the red corpuscles differ from the salts of serum 
in that the ash of corpuscles contains a high content of those salts that 
tend to form fixed organic compounds. For example, iron is present as a 
part of the hemoglobin molecule. There is an excess of potassium in 
corpuscles, present in fixed organic compounds. Only a small amount 
of sodium is present, and of calcium only a trace. 

Hemoglobin. Of the substances in the erythrocytes, by far the most 
important from every point of view is the pigment, hemoglobin. It composes 
about 90 per cent, of the total solids of the corpuscles; therefore, between 
14 and 15 per cent, of the blood itself. Hemoglobin is the most complex 
compound in the body, having a molecule of the enormous molecular weight 
of 16,669. Hemoglobin is intimately distributed throughout the stroma of 
the corpuscle, and when dissolved out it can be crystallized. 

Its percentage composition is C, 53.85; H, 7.32; N, 16.17; O, 21.84; 8,0.63 
Fe, 0.42. Jacquet gives the empirical formula for the hemoglobin of the dog, 
C7S8H 12 o5N 195 S 3 FeO 218 . The most interesting of the properties of hemo- 
globin are its powers of crystallizing and its attraction for oxygen and other 
gases under certain pressure relations. 

Hemoglobin Crystals. The hemoglobin (oxy hemoglobin) of the blood of 
various animals possesses the power of crystallizing to very different ex- 



tents. In some the formation of crystals is almost spontaneous, whereas 
in others it takes place either with great difficulty or not at all. Among 
the animals whose blood coloring-matter crystallizes most readily are the 
guinea-pig, rat, squirrel, and dog; and in these cases to obtain crystals it 
is generally sufficient to dilute a drop of recently drawn blood with water 
and to expose it for a few minutes to the air. In many instances other means 
must be adopted; e.g., the addition of alcohol, ether, or chloroform, rapid 
freezing and then thawing, the application of an electric current, a tempera- 


FIG. 119. Crystals of Oxyhemoglobin 
Prismatic, from Human Blood. 

FIG. 1 20. Oxyhemoglobin Crystals 
Tetrahedral, from Blood of the Guinea-pig. 

ture of 60 C., the addition of sodium sulphate, or the addition of decom- 
posing serum of another animal. 

The hemoglobin of human blood crystallizes with difficulty, as does also 
that of the ox, the pig, the sheep, and the rabbit. 

The forms of hemoglobin crystals, as will be seen from figures 119 and 
1 20, differ greatly. Hemoglobin crystals are soluble in water. Both the 
crystals themselves and also their solutions have the characteristic color of 
arterial blood. 

A dilute solution of Oxyhemoglobin gives a characteristic appearance 
with the spectroscope. Two absorption bands are seen between the solar 
lines D, which is the sodium band in the yellow, and E, see the frontispiece,, 
one in the yellow, with its middle line some little way to the right of D. This 
band is very intense, but narrower than the other, which lies in the green 
near to the left of E. Each band is darkest in the middle and fades away 
at the sides. As the strength of the solution increases, the bands become 
broader and deeper. Both the red and the blue ends of the spectrum become 
encroached upon until the bands coalesce to form one very broad band when 
only a slight amount of the green and part of the red remain unabsorbed. 
Any further increase of strength leads to complete absorption of the spectrum. 

If crystals of hemoglobin are exposed to an atmosphere of oxygen they 
take up oxgyen and form Oxyhemoglobin, each gram of the pigment fixing 


a definite amount oxygen, see chapter on Respiration. When subjected 
to a mercurial air-pump the oxygen is given off, and the crystals become 
of a purple color. A solution of the oxyhemoglobin in the blood corpuscles 
may be made to give up oxygen, and to change color in a similar manner. 
One gram of oxyhemoglobin liberates i . 59 c.c. oxygen, or, according to Hiif- 
ner's later determinations, i .34 c.c., see page 292. 

This change may be also effected by passing through the solution of 
blood or of oxyhemoglobin, hydrogen or nitrogen gas, or by the action of 

FIG. 121. Hexagonal Oxyhemoglobin Crystals, from Blood of Squirrel. On these 
hexagonal plates prismatic crystals, grouped in a stellate manner, not unfrequently occur 
(alter Funke). 

reducing agents, of Stokes's fluid* or ammonium sulphide are the most 

With the spectroscope, a solution of deoxidized or reduced hemoglobin 
is found to give an entirely different appearance from that of oxidized hemo- 
globin. Instead of the two bands at D and E, we find a single broader but 
fainter band occupying a position midway between the two, and at the same 
time less of the blue end of the spectrum is absorbed. Even in strong solu- 
tions this latter appearance is found, thereby differing from the strong solu- 
tion of oxidized hemoglobin which lets through only the red and orange 
rays; accordingly, to the naked eye the one (reduced-hemoglobin solution) 
appears purple, the other (oxyhemoglobin solution) red. The deoxidized 
crystals or their solutions quickly absorb oxygen on exposure to the air, 
becoming scarlet. If solutions of blood be taken instead of solutions of 
hemoglobin, results similar to the whole of the foregoing can be obtained. 

Venous blood never, except in the last stages of asphyxia, fails to show 
the oxyhemoglobin bands, inasmuch as the greater part of the hemoglobin 
even in venous blood exists in the more highly oxidized condition. 

*Stokes's fluid consists of a solution of ferrous sulphate, to which ammonia has been 
added and sufficient tartaric acid to prevent precipitation. Another reducing agent is a 
solution of stannous chloride, treated in a way similar to the ferrous sulphate, and a third 
reagent of like nature is an aqueous solution of yellow ammonium sulphide, - 


Action of Gases on Hemoglobin. Carbon monoxide gas passed through 
a solution of hemoglobin causes it to assume a cherry-red color and to 
present a slightly altered spectrum; two bands are still visible but are 
slightly nearer the blue end than those of oxyhemoglobin, see Plate I. 
The amount of carbon monoxide taken up is equal to the amount of the 
oxygen displaced. Carbon monoxide gas readily displaces oxygen under 
the ordinary respiratory conditions. It is less readily displaced by excess 
of oxygen and by carbon dioxide, hence the poisonous effects of coal gas 
which contains much carbon monoxide. Carbon monoxide hemoglobin 
is not an oxygen carrier, and death may result from suffocation due to the 
want of oxygen, notwithstanding the free entry of pure air into the lungs. 
Crystals of carbon monoxide hemoglobin closely resemble in form those 
of oxyhemoglobin. 

Nitric oxide produces a similar compound to the carbon monoxide 
hemoglobin, which is even less easily reduced. 

Sulphuretted hydrogen, if passed through a solution of oxyhemoglobin, 
reduces it and an additional band appears in the red. If the solution be 
then shaken with air, the two bands of oxyhemoglobin replace that of 
reduced hemoglobin, but the band in the red persists. 

Methemoglobin. If an aqueous solution of oxyhemoglobin is exposed 
to the air for some time, its spectrum undergoes a change; the two d and 
e bands become faint and a new line in the red at C is developed. The 
solution, too, becomes brown and acid in reaction, and is precipitable by 
basic lead acetate. This change is due to the decomposition of oxyhemo- 
globin, and to the production of methemoglobin. On adding ammonium 
sulphide, reduced hemoglobin is produced, and on shaking this up with air, 
oxyhemoglobin is again produced. Methemoglobin is probably a stage in 
the deoxidation of oxyhemoglobin. It appears to contain less oxygen than 
oxyhemoglobin, but more than reduced hemoglobin. Its oxygen is in more 
stable combination, however, than is the case with the former compound. 

Estimation of Hemoglobin. The most exact method is by the esti- 
mation of the amount of iron (dry hemoglobin containing 0.42 per cent, 
of iron) in a given specimen of blood, but as this is a somewhat complicated 
process, various methods have been proposed which, though not so exact, 
have the advantage of simplicity. Of the several varieties of hemo- 
globinometer, one of the oldest adapted to its purpose is that invented by 
professor Fleischl, of Vienna. In this instrument the amount of hemo- 
globin in a solution of blood is estimated by comparing a stratum of 
diluted blood with a standard solid substance of uniform tint similar 
spectroscopically to diluted blood. The instrument has been modified 
and made more accurate by Miescher. The Fleischl-Miescher apparatus 
consists of a stand with a metal plate having a circular opening and a 



plaster mirror below, 5, figure 122, which casts light through the opening. 
Beneath the plate is a metal framework containing a colored glass wedge, 
and along the side of the same is a scale graduated so as to indicate the 
percentage of hemoglobin corresponding to the shades of the different parts 
of the wedge. This frame- ^ a r 

work can be moved by the 
wheel T which fits into a rack 
on its lower surface. The 
scale can be read through a 
small opening M in the plate. 
Into the large circular open- 
ing of the plate fits a cylin- 
drical metal cell G with a glass 
bottom and divided by a metal 
partition into two equal parts. 
One of these halves lies over 
the wedge and is filled with 
distilled water. The other 
contains the solution of blood 

in which the hemoglobin is 

j ,-,, FIG. 122. Fleischl's Hemoglobinometer. 

to be estimated. The appar- 
atus is usually supplied with three cells. Of these, the first two are 
used in estimating the hemoglobin according to Miescher. This is the 
method now generally used. These cells are furnished with a glass cover 
having a groove whicn fits upon the partition of the cell. Over this cover 
is placed a diaphragm with a longitudinal slit, which only permits of 
the central part of each side of the cell being seen. 

The patient's ear or finger is pricked, and the blood from the wound 
sucked up into the graduated pipet until it reaches the mark J, , or -f, a 
i per cent, solution of sodium carbonate is then sucked in until the upper 
mark is reached. The pipet is then well shaken in order to mix the blood 
thoroughly. One-half of each of the two cells, which are, respectively, 12 
and 15 millimeters high, is then filled with the mixture, the other half 
being filled with water. An important point is that the liquids should com- 
pletely fill the cells. The cover-glasses and diaphragms are then applied 
, and the cells are ready for examination. This must be done by artificial 
light. Moreover, in order to have accurate results, light of the same inten- 
sity should be always used. One of the cells is placed on the plate and the 
wheel T turned until the colors of the two halves exactly correspond. When 
this point is reached, the result is read off on the scale through the opening 
M. This should be repeated several times with each of the cells, and the 
average of the readings taken. The result obtained with the 1 2-millimeter 


cell should be multiplied by f to bring it up to that of the larger. For example, 
suppose the result of several readings to be: 

With the large cell (15 mm.) 54 . oo 

With the small cell (12 mm.) 42 .00 

If the readings obtained with the large cell are exactly correct, then the read- 
ings with the smaller one should be 43.2, since 54 X =43.2. Or, if the 
readings with the smaller cells are exact, the readings with the larger should 
be 52. 5, since 42 Xf =52.5. Hence the mean of 54 and 52.5, namely 53.25, 
should be taken as the correct figure. On looking at the corrected table of 
hemoglobin values supplied with each instrument, we would find that this 
number on the scale corresponds to a solution containing 400 milligrams 
of hemoglobin per 1000 cubic centimeters of solution. But our original dilu- 
tion was either i : 200, i : 300, or i : 400, according as our pipet had been 
filled with blood up to the mark -}-, , or J; so that in order to obtain the actual 
percentage of hemoglobin in the blood under examination we should be 
obliged to multiply our results by 200, 300, or 400. In the example we have 
taken, the amount of hemoglobin would be, if our dilution was i : 200, 400 X 
200=80,000 milligrams = 80 grams in 1,000 cubic centimeters = 8 grams 
in 100 cubic centimeters, or 8 per cent. 

The Dare's hemoglobinometer avoids the error of diluting blood by 
comparing undiluted blood under artificial light with a colored scale which 
is graduated after standardization against a hemoglobin content of normal 
blood, i.e., 13.77 grams of hemoglobin per 100 cubic centimeters. The 
instrument, see figure 1220, consists of a blood pipette, a case inclosing the 
color comparison disc, and is provided with a small telescope for reading 
the color contrasts against an artificial candle light. A drop of blood is 
drawn with a lancet from a finger tip or the lobe of the ear, is allowed to 
run directly between the plates of the pipette where it spreads by capil- 
larity. The gradations on the comparison scale are read under candle 
light and the computations for the percentage of hemoglobin in the sample 
made against the normal. Its ease of manipulation and comparative 
accuracy gives to this method the status of a clinical favorite. Another 
clinical method somewhat less readily manipulated is that of Sahli. 

The Talquist method enables one to make a quick approximation of 
the hemoglobin content. It is valuable as a preliminary test to the Dare 
and is sufficiently accurate for many clinical determinations. 

This consists of a series of shades of color corresponding to undiluted 
blood of various hemoglobin values, ranging from 10 to 100 per cent, of an 
arbitrary scale. This scale is included in a book, the remaining pages of 
which consist of filter-paper, which is used for absorbing the specimen of 
blood whose hemoglobin percentage is to be estimated. The blood- 
stained filter-paper is compared with the hemoglobin scale by direct day- 


light until a shade is found with which it corresponds. For approxi- 
mate results this method has proved very satisfactory. 


FIG. 1220. Dare Hemoglobinometer. Instrument ready for use, illustration one- 
half actual size. R, Milled wheel by which the color prism is rotated by friction exerted 
upon its edge. S, Case enclosing color prism, showing stage upon which the blood 
pipet slides. T, Movable wing pivoted to case. When drawn outward screens the 
eyes of observer from the light. When not in use lies superimposed upon the circular 
prism case, occupying no extra space. U, Telescoping camera tube in position for 
examination. V, Opening in prism case, admitting light for illumination of color prism. 
The white glass disc of prism is seen inside. W, White glass of blood pipet. X, Pipet 
clamp held in position on the stage by grooves and guides. F, Detachable candle- 
holder. Z, Rectangular opening in edge of case for reading hemoglobin percentage 
indicated by beveled blade. L, Light (candle or electric.) Color prism. E, Prism of 
colored glass. F, Semi-circle of white glass, the edge carrying the index of hemoglobin 
percentage in black; this edge also serves as a friction surface for the rubber-covered roller 
by which the prism is rotated. G, Hole in which hub is fixed. H, Index of hemoglobin 
percentage etched in black. 7, Disc of white glass which serves to break the glare of 
direct light and furnishes a white background to view the shades of color. 

Derivatives of Hemoglobin. Hematin. By the action of heat or 
of acids or alkalies in the presence of oxygen, hemoglobin can be split up 
into a substance called hematin, which contains all the iron of the hemo- 
globin from which it was derived, and a protein residue, a histone, globin. 
If there be no oxygen present, instead of hematin a body called hemochro- 
mogen is produced, which, however, will speedily undergo oxidation into 

Hematin is a dark brownish or black non-crystallizable substance of 
metallic luster. Its percentage composition is C, 64.30; H, 5.50; N, 9.06; 
Fe, 8.82; O, 12.32; which gives the formula C 68 H 70 N 8 Fe 2 O 10 (Hoppe- 
Seyler). It is insoluble in water, alcohol, and ether; soluble in the caustic 
alkalies; soluble with difficulty in hot alcohol to which is added sulphuric 
acid. The iron may be removed from hematin by heating it with fuming 


hydrochloric acid to 160 C., and a new body, hematoporphyrin, the so-called 
iron-free hematin, is produced. Hematoporphyrin (C 88 H 74 N 8 O 12 , Hoppe- 
Seyler) may also be obtained by adding blood to strong sulphuric acid, and 
if necessary filtering the fluid through asbestos. It forms a fine crimson 
solution, which has a distinct spectrum, viz., a dark band just beyond D, 
and a second all but midway between D and E. It may be precipitated from 

FIG. 123. Hematoidin Crystals. (Frey.) FlG. I23a. Hemin Crystals. (Frey.) 

its acid solution by adding water or by neutralization, and when redissolved 
in alkalies presents four bands, a pale band between C and D, a second 
between D and E, nearer D, another nearer E, and a fourth occupying the 
chief part of the space between b and F. 

Hematin in Acid Solution. If an excess of acetic acid is added to blood, 
and the solution boiled, the color alters to brown from decomposition of 
hemoglobin and the setting free of hematin; by shaking this solution with 
ether, a solution of hematin in acid solution is obtained. The spectrum of 
the ethereal solution shows no less than four absorption bands, viz., one in 
the red between C and D, one faint and narrow close to D, and then two 
broader bands, one between D and E, and another nearly midway between 
b and F. The first band is by far the most distinct, and the acid aqueous 
solution of hematin shows it plainly. 

Hematin in Alkaline Solution. If a caustic alkali is added to blood and 
the solution is boiled, alkaline hematin is produced, and the solution becomes 
olive-green in color. The absorption band of the new compound is in the 
red, near to D, and the blue end of the spectrum is absorbed to a considerable 
extent. If a reducing agent be added, two bands resembling those of oxy- 
hemoglobin, but nearer to the blue, appear; this is the spectrum of reduced 
hematin, or hemochromogen. On violently shaking the reduced hematin 
with air or oxygen the two bands are replaced by the single band of alkaline 

Hematoidin. This substance is found in the form of yellowish crystals, 
figure 123, in old blood extravasations and is derived from the hemoglobin. 
Their crystalline form and the reaction they give with fuming nitric acid 
seem to show them to be closely allied to bilirubin, the chief coloring matter 
of the bile, and in composition they are probably either identical or isomeric 
with it. 

Hemin. One of the most important derivatives of hematin is hemin. 
It is usually called hydrochloride of hematin, but its exact chemical com- 


position is uncertain. Its formula is said to be C 32 H 30 N 4 FeO 3 HCl, and it 
contains 5.18 per cent, of chlorine, but by some it is looked upon as simply 
crystallized hematin. Although difficult to obtain in bulk, a specimen may 
be easily made for the microscope in the following way: A small drop of 
dried blood is finely powdered with a few crystals of common salt on a glass 

Hemoglobin + Oxygen z Oxyhemoglobin -*. Methemoglobin 

on heating with XV on heating with on treating with 

acidulated alcohol / \ acidulated alcohol potassium ferri- 

cyanide, etc. 


Hemochromogen Hematin Globin 

with strong / \ heat with 
sulphuric and / \ glacial acetic 
hydrobromic acids / \ acid and sodium 

/ \chloride 

/ * 

Hematoporphyrin Hemin 

(Iron-free hematin. (Hematin hydrochloride) 

isomeric or identical 
with bilirubin.) 

on reduction, with Stoke's reagent, etc. 

Scheme to Show the Relations of Hemoglobin and its Derivatives. 

slide and spread out; a cover-glass is then placed upon it, and glacial acetic 
acid added by means of a capillary pipet. The blood at once turns a brown- 
ish color. The slide is then heated, and the acid mixture evaporated to 
dryness at a high temperature. The excess of salt is washed away with 
water from the dried residue, and the specimen may then be dried and 
mounted. A large number of small, dark, reddish-black crystals of a rhom- 
bic shape, sometimes arranged in bundles, will be seen if the slide be sub- 
jected to microscopic examination, figure 123%. 

The formation of these hemin crystals is of great interest and importance 
from a medico-legal point of view, as it constitutes the most certain and 
delicate test we have for the presence of blood (not of necessity the blood 
of man) in a stain on clothes, etc. It exceeds in delicacy even the spectro- 
scopic test. Compounds similar in composition to hemin, but containing 
hydrobromic or hydriodic acid, instead of hydrochloric, may be also readily 

Variations in the Composition of Healthy Blood. The conditions 
which appear most to influence the composition of the blood in health are 
these: Diet, Exercise, Sex, Pregnancy, and Age. 

Sex. The blood of men differs from that of women, chiefly in being of 
somewhat higher specific gravity, from its containing a relatively larger 
quantity of red corpuscles. 

Pregnancy. The blood of pregnant women has rather lower than the 
average specific gravity. The quantity of the colorless corpuscles is in- 
creased in the later months, especially in primiparae; it is also claimed that 
the fibrin is increased in amount. 


Age. The blood of the fetus is very rich in solid matter, and especially 
in colored corpuscles; and this condition, gradually diminishing, continues 
for some weeks after birth. The quantity of solid matter then falls during 
childhood below the average, rises during adult life, and in old age falls again. 

Diet. Such differences in the composition of the blood as are due to the 
temporary presence of various matters absorbed with the food and drink, 
as well as the more lasting changes which must result from generous or poor 
diet, respectively, need be here only referred to. 

Effects of Bleeding. The result of bleeding is to diminish the specific 
gravity of the blood, and so quickly that in a single venesection the portion 
of blood last drawn has often a less specific gravity than that of the blood that 
flowed first. This is, of course, due to absorption of fluid from the tissues 
of the body. The physiological import of this fact, namely, the instant 
absorption of liquid from the tissues, is the same as that of the intense thirst 
which is so common after either loss of blood or the abstraction from it of 
watery fluid, as in cholera, diabetes, and the like. 

For some little time after bleeding, the want of colored corpuscles is well 
marked, but with this exception no considerable alteration seems to be 
produced in the composition of the blood for more than a very short time; 
the loss of the other constituents, including the colorless corpuscles, being 
very quickly repaired. 

Variations in Different Parts of the Body. The composition of the blood, 
as might be expected, is found to vary in different parts of the body. Thus 
arterial blood differs from venous; and although its composition and general 
characters are uniform throughout the whole course of the systemic arteries, 
they are not so throughout the venous system, the blood contained in some 
veins differing markedly from that in others. 

Differences between Arterial and Venous Blood. The differences between 
arterial and venous blood are these: 

Arterial blood is bright red, from the fact that almost all its hemoglobin 
is combined with oxygen, oxyhemoglobin, while the dark red tint of venous 
blood is due to the deoxidation of a certain quantity of its oxyhemoglobin, 
and its consequent reduction to the hemoglobin. 

Arterial blood coagulates somewhat more quickly. 

Arterial blood contains more oxygen than venous and less carbon 
dioxide gas. 

Some of the veins contain blood which differs from the ordinary standard 
considerably. These are the portal, the hepatic, and the splenic veins. 

Portal Blood. The blood which the portal vein conveys to the liver is 
supplied from two chief sources; namely, from the gastric and mesenteric 
veins, which contain the soluble elements of food absorbed from the stomach 
and intestines during digestion, and from the splenic vein. It must, there- 
fore, combine the qualities of the blood from each of these sources. 


The blood in the gastric and mesenteric veins will vary much according 
to the stage of digestion and the nature of the food taken, and can therefore 
be seldom exactly the same. Speaking generally and without considering 
the sugar and other soluble matters which may have been absorbed from 
the alimentary canal, this blood appears to be deficient in solid matters, 
especially in colored corpuscles, owing to dilution by the quantity of water 
absorbed, to contain an excess of protein matter, and to yield a less tenacious 
kind of fibrin than that of blood generally. 

The blood of the portal vein, combining the peculiarities of its two factors 
the splenic and mesenteric venous blood, is usually of lower specific gravity 
than blood generally, is more watery, contains fewer colored corpuscles, 
more proteins, and yields a less firm clot than that yielded by other blood, 
owing to the deficient tenacity of its fibrin. 

Guarding (by ligature of the portal vein) against the possibility of an 
error in the analysis from regurgitation of hepatic blood into the portal vein, 
recent observers have determined that hepatic venous blood contains less 
water, proteins, and salts than the blood of the portal veins; but that it 
yields a much larger amount of extractive matter, in which is one constant 
element, namely, glucose, which is found whether carbohydrates have 
been present in the food or not. 


Cytolysis. It has been known for some time that the sera of certain 
animals when injected into the circulation of animals of another species will 
cause destructive changes in the blood corpuscles, accompanied by 
symptoms of poisoning, which may even end fatally. These results served 
to bring into disrepute the use of foreign blood in transfusion, which has 
consequently been practically abandoned. The discharge of the hemo- 
globin of the red blood corpuscles and their solution in the plasma (laking) 
is now included in the general term Cytolysis, and more specifically known 
as Hemolysis. Agents which produce such an effect are known as hemolytic 
or hemotoxic agents. 

Transfusion of the blood of one animal into the vessels of another is 
often quickly fatal because of the hemolytic reactions of the two bloods. 
Transfusions between different species or distantly related animals are as a 
rule not possible. But the blood of different individuals of the same 
species are usually not lytic. This subject possesses great importance 
to man because of the growing practice of blood transfusions in man. 
However not all human bloods can be blended without great danger though 
as a rule members of the same family are miscible. Human bloods must 
first be tested or typed, as it is called, to determine whether or not lysis 


would occur on transfusion. Four human types have been described by 
serologists. No transfusion is now ever performed without this pre- 
liminary test which is absolutely necessary lest immediate solution of the 
red corpuscles be produced and the death of the recipient follow. 

The serum of one animal may be made to acquire lytic properties for 
the blood of another. This adaptation is brought about in the following 
way: For instance, the blood of the guinea-pig, which is not normally 
lytic for the red cells of the rabbit, may be adapted to the latter by pre- 
viously, at several successive intervals (three to seven days) injecting into 
the abdominal cavity or subcutaneous tissues of the guinea-pig small 
quantities of rabbit's blood. If now a small quantity of serum be obtained 
from the guinea-pig by the usual methods and mixed in a test-tube with 
some of the rabbit's blood diluted with physiological salt solution, hemoly- 
sis occurs; that is, the coloring matter of the rabbit's red blood-cells goes 
into solution and the cells appear under the microscope as shadow cor- 
puscles or ghosts, devoid of hemoglobin. Such an artificially produced 
hemolytic serum is only lytic for the blood of the animal species for which 
it has been adapted. It is true that it may also show slightly lytic 
properties for closely allied species. It has therefore been suggested as a 
possible valuable aid in determining relationships of various animal 

Concerning the nature of the lytic substance, it has been found that it 
probably consists of two bodies acting conjointly, for if the serum be heated 
to 56 C. for a short time, its lytic powers are lost, but may be restored by 
adding a little serum of another animal of the same species which has not 
been adapted, and whose serum is consequently not in itself lytic. Of these 
two bodies, therefore, one is stable and is formed only in the adapted serum, 
while the other is more unstable or labile, destroyed at 56 C., and exists 
normally in the blood plasma. The former is known as the immune body, 
the amboceptor, and the latter as the alexin, or complement. Lysis occurs 
only when both are present at the same time, and not through the agency of 
one or the other singly. 

This cytolytic adaptation has been extended to include other cells besides 
the red blood corpuscles. Thus in a similar manner leucolytic, hepatolytic, 
nephrolytic, and a number of other lytic sera have been developed. 

It is further possible, under certain circumstances, that substances may 
be developed in the tissues which are lytic for other tissue cells of the same 
animal, autolytic substances. This may be a physiologically important process 
in the elimination of worn-out tissue cells, cellular elements in injury, in- 
flammation, etc. 

Agglutinative Substances. A further property of adapted sera is 
that of agglutination. The adaptation is secured in the same way as in 


the production of cytolysins. In fact, both cytolysis and agglutination may 
occur at the same time. The normal blood serum of some animals may 
be agglutinative for the blood-cells of some other species. In normal serum, 
agglutinative and cytolytic properties may be present together or one only 
may be normally present. 

The activity of agglutinative substances is not destroyed at a tempera- 
ture of 56 C. They do become inert, however, at 70 C., and, furthermore, 
they cannot be restored by adding normal serum, as is the case with cytolysins. 

Hemagglutinative substances are found in certain plant seeds; e.g., in 
castor oil beans (Ricinus communis) , in cotton seed, and in the legumes. 

Precipitins. Other forms of adaptive substances which may be found 
in animal serum are those which, when mixed with the substances by means 
of which adaptation has been secured, form a precipitate. By this means 
blood of different species of animals may be detected even when in a dried 
state. It has been suggested as a possible valuable aid in medico-legal 
cases, since human blood in a dilution of i to 50,000 has been recognized 
by this means. 

Opsonins. Wright and Douglass have shown that there are certain 
substances in the serum that affect bacteria in such a way that they are more 
easily taken up and destroyed by leucocytes. The phagocytic power of the 
leucocytes in destroying toxic bacteria is not made to increase by stimulative 
substances, as Metchnikoff believed, but rather by those materials in the 
serum diminishing the resisting power of the bacteria. These substances 
are called by their discoverers opsonins. They found opsonin present in 
normal serum, but also found that its quantity varies under certain conditions. 
They suggested that the opsonins could be measured by determining the 
phagocytic power. The ratio of the average number of bacteria taken up by 
leucocytes in normal serum to the number taken up in the immune serum, 
they called the opsonic index. 

Antitoxins. Certain kinds of bacteria, notably the diphtheria and 
tetanus organisms, elaborate poisonous substances known as toxins. The 
pathological conditions resulting from such infections are produced by the 
poisons so formed. Behring first showed that immunity to diphtheria was 
due to the presence in the blood plasma and blood serum of substances which 
apparently combine with and so prevent the toxic action of the bacterial 
products. This antitoxic power of the blood can be artificially developed by 
injecting small doses of the toxins into an animal, usually a horse, at inter- 
vals of some days. The protective power of the blood against the toxins can 
thus be developed to a relatively enormous degree. The serum of an arti- 
ficially immunized animal can be injected into other individuals of the same 
or other species and an immunity will be conferred on the person or animal 
so treated. Similarly, the antitoxic sera have a curative effect in infected 
individuals if the disease is not too far advanced. Antitoxic sera are specific 


for the particular toxin used for the immunization. Antitoxins can be 
similarly prepared for the naturally occurring vegetable toxins, ricin and 
abrin, for snake venoms, etc. 

Anaphylaxis. It has been found that if an animal, especially the 
guinea pig, be injected with even the minutest quantity of protein material, 
that after ten to fourteen days, the animal becomes susceptible to a sec- 
ond injection of the same material if made intravascularly. Thus a guinea 
pig may be sensitized with o.oooooi of a c.c. of blood serum; after two 
weeks have elapsed, the introduction of a half c.c. of the same serum into 
the circulation will in a few minutes lead to respiratory failure and death. 
This phenomenon is relatively specific for foreign protein substances. 
Guinea-pigs which have recovered from the second injection acquire a 
temporary immunity against a third injection of the same protein. It has 
been found that this peculiar susceptibility is transferred from the mother 
guinea-pig to successive litters. 

Nature of the Antisubstances in Blood. The lecithins and fatty acids, 
especially oleic acid, will in a measure replace a hemolytic complement. 
The antitoxins and agglutinins in the blood seem either to be associated 
with, or actually are a portion of, the para- or pseudoglobulin. During im- 
munization, the pseudoglobulin of the blood may be twice the normal con- 
tent; coincidently the per cent, of the serumalbumin will diminish. The 
protein changes in the blood of horses and the antitoxic variations, how- 
ever, are not parallel, and no quantitative relationship has been established. 


Diffusion, Osmosis, Dialysis. The term diffusion has long been ap- 
plied to the regular mixing of the molecules of two gases when brought 
into contact in a confined space, this interpenetration being due to the 
to-and-fro movements of their molecules. More recently it has been 
applied to the mixing of the molecules of two solutions when brought into 
contact, as it has been found that they act in the same way and obey the 
same laws as gases. If, however, the two solutions are separated by a 
membrane, permeable to the solutions, diffusion will still occur. To this 
form of diffusion the term osmosis has been applied in the case of water, 
and dialysis in the case of diffusible substances. All bodies can be 
divided into two groups, crystalloids and colloids. To the former group 
belong bodies having a crystalline form, which readily go into solution 
in water. All such bodies are diffusible (dialyzable), their power of 
dialysis, however, varying considerably. To the second group belong 
such bodies as have no crystalline form (amorphous). These are generally 
bodies with a large molecule, which form colloidal suspensions in water and 
are only slightly or not at all diffusible. An exception to the first group 
is hemoglobin, which has a very large molecule, and is crystalline but is 


not diffusible. The following may serve as simple illustrations: 

Take a jar and divide it in two equal parts by an animal membrane, M, 
figure 124, and place an equal amount of distilled water in the two sides, A 
and B. Now, since the molecules of water act like those of a gas and are 
continually moving to and fro, bombarding all the surfaces of their retainer, 
the molecules of water in A and B will be continually striking all the surfaces 
of A and B; but since the membrane is permeable to 
the water molecules, there will be a continual inter- 
change of molecules between A and B. If now, in one 
side A we place a solution of sodium chloride, still 
keeping water in B, the membrane being permeable to 
the sodium chloride, the first thing we should notice 
would be an increase in the amount of water in A. For- 




FIG. 124. FIG. 125. 

merly it would have been said that " the salt had attracted the water." Now 
we should say that the salt had a certain osmotic pressure. The salt, how- 
ever, being able to pass (dialyse) through the membrane, will do so, and this 
will continue until the strength of the two salt solutions, and therefore the 
osmotic pressure on both sides, is equal. 

Osmotic Pressure. If now in A we place a solution of some soluble 
colloidal substance to which the membrane is impermeable, or else replace 
the membrane, M, we used in our former experiment by one which is not 
permeable to the sodium chloride, and arrange our jar as in figure 125, so 
as to be able to read off any increase of water which may pass into A, we 
will notice that the amount of liquid in A will continue to increase up to a 
certain point. Once that point is reached, there will be no further change, 
since the substance in solution, in A , cannot pass through the membrane as 
in the previous example. This pressure can be measured and expressed in 
millimeters of mercury. It is constant for all solutions of this substance 
that are of the same concentration when measured under like conditions of 
temperature and pressure, and is called the osmotic pressure of this solution. 

Of the numerous explanations regarding the nature of osmotic pressure 
which has been more or less satisfactory, a simple one, and one that can 


be easily understood, is as follows: In figure 125 one surface of the mem- 
brane is being bombarded by the molecules of a non-diffusible substance 
mixed with those of a diffusible one (water) ; while the other surface is being 
bombarded entirely by water molecules. The former condition permits 
only a fraction of the molecules to diffuse out, since fewer water molecules 
get to the surface of the membrane; while the latter permits all of the 
molecules which reach it to pass through. 

Osmotic pressure can be estimated in several different ways in addition 
to the above, viz., the determination of the freezing-point of the solution, 
determination of the boiling-point, determination of the electrical conduc- 
tivity. The results obtained with the various methods agree very closely. 
The following solutions have the same osmotic pressure: Sodium chloride, 
i . 64 per cent. ; potassium nitrate, i . 09 per cent. ; sugar 5 . 5 per cent. 

Isotonic Solutions. Solutions that have the same osmotic pressure 
are called isotonic. The term isotonic is a relative one, implying a compari- 
son with some other solution taken as a standard. In physiology it has been 
customary to take blood plasma as a standard. A solution of o . 64 per cent, 
sodium chloride is isotonic for the blood plasma of the frog, and a o . 9 per 
cent, solution for that of man. Further, any solution which is of a lower 
osmotic pressure than the standard solution is said to be hypoisotonic (hypo- 
tonic) in relation to that solution. A solution of a higher osmotic pressure 
is said to be hyperisotonic (hypertonic}. 

Water passes in the Direction of the Arrows. 
Hypertonic saline solution (2 per cent.) 




Isotonic saline solution (o . 64 per cent.) 


Hypotonic saline solution (o-3 per cent.) 

If a hypotonic solution be mixed with blood, water from the hypotonic 
solution passes through the cell membrane of the red corpuscles into the 
stroma and causes it to swell. The hemoglobin at the same time passes 
out and goes into solution in the diluted plasma. On the other hand, the 
addition of a hypertonic solution to the plasma causes the red corpuscles 
to lose their water and become crenated. The principles of osmosis have 
been derived from the action of substances separated by dead animal or 
plant membranes. It must be, however, remembered that in the applica- 
tion of these principles to processes occurring in the living organism, the 
cells, forming the various membanes, are an important modifying factor. 
It is probable that physico-chemical processes, occurring in the protoplasm 
of the cell, may change its permeability to the same substance at different 


The lymph is the fluid which immediately surrounds the tissue cells of 


the living body. It fills up the spaces between the cells themselves and 
between the cells and the blood vessels which ramify among the cell masses. 
The lymph, therefore, is an intermediate fluid between blood plasma on the 
one hand and the tissue cells on the other, receiving its ingredients by the 
passage of fluid from the plasma through the walls of the finer blood vessels 
in the one direction and by the discharge of the substances from the cells 
themselves in the other. 

The Chemical Composition of the Lymph. Since the chief source 
of the lymph is the blood plasma, one would naturally expect that its chemi- 
cal composition would be very similar to that of plasma, which is in fact the 
case. The variations that are noted in lymph taken from definite sources no 
doubt have their origin in the fact that the lymph passes through these 
organs slowly, and that ingredients peculiar to the necessities of the func- 
tion and growth of the differentiated tissue of the organ are taken from the 
lymph in special organs. Lymph obtained from a human lymphatic fistula 
has been analyzed; the figures from Hammarsten are as follows, though 
considerable variations appear in the analyses from other authorities: 


Per cent. 

Water 94-5 to 96 . 5 

Solids 3.5 to 5.5 

Proteins 3.4 to 4.1 

Ethereal extract o . 06 to 0.13 

Sugar o.i 

Salts 0.8 to 0.9 

Sodium chloride -55 to 0.58 

Sodium carbonate 0.24 

Disodic phosphate 0.028 

The most notable fact to be derived from this composition table is the 
low percentage of proteins present in the lymph. 

The Formation of Lymph. The manner in which the substances in 
the lymph pass through the walls of the capillaries from the plasma is a 
question which has been surrounded with considerable difficulty. It was 
thought by Ludwig and many of his followers that the process involved 
is merely one of filtration. Certainly the blood-pressure in the capillaries 
is in the main greater than that of the pressure of the lymph in the surround- 
ing tissues, and this positive pressure will contribute so much to the direct 
ingredients of the blood plasma through the capillary walls. It is true, as a 
matter of experiment, that anything which contributes to an increase in 
the capillary pressure is very apt to produce an edema of the corresponding 
tissues. Since the colloidal materials represented by the protein are non- 
diffusible, one would by this theory expect to find a diminished percentage 
in the lymph, which is true, though not to the extent which the theory 


Heidenhain was the first to question the adequacy of the blood-pres- 
sure and filtration hypothesis. He showed that many of the conditions 
under which lymph formation takes place are not sufficient to produce filtra- 
tions of the material found. He advanced the hypothesis that the living 
endothelial lining of the blood vessels exerted a secretory activity in lymph 
production. He discovered that various substances known as lymphagogues 
when introduced into the circulatory system produce a remarkable increase 
in the flow of lymph from the thoracic duct. Further, he noticed that the 
concentration of the lymph was changed; i.e., increased. Heidenhain 
thought that the lymphagogues acted directly on the capillary and endothelial 
lining stimulating these cells to produce a greater quantity of lymph. He 
divided such substances into two classes. The best known representatives 
of the " first class" are such as proteoses and peptones, leech extract, ex- 
tract of crustacean tissue, etc. The lymphagogues of the second class are 
the neutral inorganic salts, sugars, and other crystalline substances. These 
all cause a marked flow of lymph. The lymphagogues as a class cause fall 
of blood-pressure; for example, proteose-peptone injections. This fact 
argues against their purely physical action. Many drugs act to increase 
the flow of lymph in a way which cannot be presumed to be other than nor- 
mal; i.e., they stimulate the physiological processes going on in the endo- 
thelial cells. Such observations contribute strongly to the view advanced 
by Heidenhain. Many investigations have been brought to the support of 
the hypothesis that lymph formation is largely a process of secretion, yet 
it seems at the present time that we cannot wholly deny that filtration and 
osmosis play a part in the processes. 

In following the action of peptones and proteoses, Pick and Spiro came 
to the conclusion that it was not peptone, but some contaminating substance 
which produced the characteristic action. This hypothetical substance 
they called peptozyme. Underhill re-examined the influence of peptones, 
using preparations made from plant proteins by hydration with enzymes, 
heat, and acid, carrying the hydrolysis to a greater extent than did Pick and 
Spiro. Underhill still obtained the great increase in the flow of lymph 
together with the usual fall of blood-pressure. Mendel published the 
result of a demonstration of post-mortem lymph flow in which he showed 
that ' ' the lymph continued to flow for four hours without any extraordinary 
mechanical assistance" after the death of the animal. This observation 
would seem to give complete refutation of the filtration hypothesis. A 
similar post-mortem salivary secretion has been observed, and in each case 
the processes involved must be assumed to be physiological rather than 
purely physical phenomena. Certainly the permeability or activity of the 
endothelial lining of the blood vessels varies greatly at different times in 
the life of an individual, and this variation in function is associated with the 
marked change in the character and quantity of lymph produced. 




1. Microscopical Examination of the Blood. Mount a drop of frog's 
blood in o . 7 per cent, sodium chloride and examine with the high power of a 
compound microscope. The red corpuscles will appear as oval nucleated 
discs with a faint yellowish color, figure no. Here and there white granular 
cells of irregular outline will be noted, the white corpuscles. Examine the 
drop of blood with a high magnifying power (oil-immersion lens) and 
sketch the outline of the blood-cells. Select the white corpuscle which is 
most irregular in outline and make a series of outline drawings once every 
minute to show its ameboid movements, figure 117. 

Draw a drop of your own blood by puncturing the tip of the finger, under 
sterile conditions, and mount in a drop of o . 9 per cent, physiological saline. 
Examine with a high power, note the small biconcave red corpuscles which 
appear faintly yellow in color and even adhere in rouleaux, figure 109. The 
white corpuscles will appear as somewhat larger granular discs differing in 
form and size. By mounting a drop of blood on a warm stage the ameboid 
movements of the white corpuscles can be observed with comparative ease. 

2. Action of Fluids on the Red Corpuscles. Water. When water is 
added gradually to frog's blood, the oval disc-shaped corpuscles become 
spherical and gradually discharge their hemoglobin, a pale, transparent 
stroma being left behind. Human red blood-cells change from a discoidal 

FIG. 126. FIG. 127. FIG. 128. FIG. 129. 

FIG. 126. Effect of Hypertonic Salt Solution on the Red Blood Corpuscles of Man. 
PIG. 127. Effect of Acetic Acid. FIG. 128. Effect of Tannin. FIG. 129. Effect 
of Boric Acid. 

to a spheroidal form and discharge their cell contents, becoming quite trans- 
parent and all but invisible (ghost corpuscles). 

Hypertonic Salt Solutions. Mount a drop of human blood in 2 per cent, 
sodium- chloride solution. The red blood-cells lose their disc shape and be- 
come spherical with spinous projections or crenations, figure 126. 

The original form of the red blood-cells can be restored by transferring 
them to isotonic salt solution. 

Dilute Acetic Acid. This reagent causes the nucleus of the red blood- 
cells in the frog to become more clearly defined; if the action is prolonged, 
the nucleus becomes strongly granulated, and all the coloring matter seems 
to be concentrated in it, the surrounding cell substance and outline of the cell 
becoming almost invisible; after a time the cells lose their color altogether. 


The cells in figure 127 represent the successive stages of the change. A 
similar loss of color occurs in the red cells of human blood, which, from the 
absence of nuclei, seem to disappear entirely. 

Alkalies. Alkalies cause the red blood corpuscles to absorb water and 
finally to disintegrate. 

Chloroform and Ether. These reagents when added to the red blood- 
cells of the frog cause them to part with their hemoglobin; the stroma of the 
cells becomes gradually broken up. A similar effect is produced on the 
human red blood-cell. 

Tannin and Boric Acid. When a 2 per cent, fresh solution of tannic acid 
is applied to frog's blood it causes the appearance of a sharply defined little 
knob, projecting from the free surface (Roberts' macula}. The coloring 
matter becomes at the same time concentrated in the nucleus, which grows 
more distinct, figure 128. A somewhat similar effect is produced on the 
human red blood corpuscle. 

A 2 per cent, solution of boric acid applied to nucleated red blood-cells of 
the frog will cause the concentration of all the coloring matter in the nucleus; 
the colored body thus formed gradually quits its central position, and comes 
to be partly, sometimes entirely, protruded from the surface of the now 
colorless cell, figure 129. The result of this experiment led Briicke to dis- 
tinguish the colored contents of the cell (zoo'id) from its colorless stroma 
(ecoid). When applied to the non- nucleated mammalian corpuscle its effect 
merely resembles that of other dilute acids. 

3. Phagocytosis in White Corpuscles. Mix some very fine pigment 
granules, bacterial emulsion, or charcoal with a few drops of frog's blood, 
let stand for 10 or 20 minutes, then mount a drop on the glass slide or 
make a smear and stain and examine under a high- magnifying microscope. 
Or inject a few drops of one of these pigments suspended in physiological 
saline and after a few minutes examine drops of the blood as above. In a 
favorable field here and there will be found some white corpuscles which 
have taken up the pigment. Colored corpuscles have been observed with 
fragments of pigment embedded in their substance. White corpuscles 
have also been seen in diseased states of the body to contain micro-organisms, 
for example bacilli, and have the power of destroying these organisms, which 
gives them the name phagocytes. 

4. Enumeration of the Blood Corpuscles. Several methods are 
employed for counting the blood corpuscles, most of them depending upon 
the same principle; i.e., the dilution of a minute volume of blood with a 
given volume of a colorless solution similar in specific gravity to blood plasma, 
so that the size and shape of the corpuscles are altered as little as possible. 
A minute quantity of the well-mixed solution is then taken, examined 
under the microscope, either in a flattened capillary tube (Malassez) or in 
a cell (Hayem and Nache, Cowers) of known capacity, and the number of 



corpuscles in a measured length of the tube or in a given area of the cell 
is counted. The length of the tube and the area of the cell are ascertained 
by means of a micrometer scale in the microscope ocular; or, in the case of 





FIG. 130. Section of the new Bausch and Lomb form of the Thoma-Zeiss Hemacy- 
tometer. This form has the advantage of having the two standard graduated scales 
reproduced in the next figure ground in the glass slide itself. 

Gowers's modification, by the division of the cell area into squares of known 
size. Haying ascertained the number of corpuscles in the diluted blood, it 
is easy to find out the number in a given volume of normal blood. 

The hemacytometer, which is most used at the present time, is known 
as the Thoma-Zeiss hemacytometer. It consists of a 
carefully graduated pipet, in which the dilution of the 
blood is done; this is so formed that the capillary stem 
has a capacity equaling one-hundredth of the bulb above 
it. If the blood is drawn up in the capillary tube to 
the line marked i, figure 131, the saline solution may 
afterward be drawn up the stem to the line 101 ; in 
this way we have 101 parts of which the blood forms i. 
As the content of the stem can be displaced unmixed we 
shall have in the mixture the proper dilution. The 
blood and the saline solution are well mixed by shak- 

Neubauer Ruling Fuchs-Rosenthal Ruling 

FIG. 1300. Standard hemacytometer rulings, 1/400 square 

FIG. 131. Thoma- 
Zeiss Hemacytome- 
ter, pipet. 

ing the pipet, in the bulb of which is contained a small glass bead for the 
purpose of aiding the mixing. The counting instrument consists of a glass 
slide, figure 130, provided with a depressed area the surface of which is 


accurately ruled so as to present one square millimeter divided into 400 
squares of one-twentieth of a millimeter each. In the older instruments 
the rulings are on the cover disc. The micrometer surface is ground 
below the general surface exactly one-tenth millimeter. If a drop of the 
diluted blood be placed upon the ruled surface, and covered with a per- 
fectly flat cover-glass, the volume of the diluted blood above each of 
the squares of the micrometer, i.e., above each 3^oo square millimeter area 
will be J^ooo f a cubic millimeter. An average of ten or more squares is 
then counted, and this number multiplied by 4000 X 100 gives the number 
of corpuscles in a cubic millimeter of undiluted blood. A separate pipet 
is used for making dilutions for counts of leucocytes. In this, the dilution 
is made of one part of blood and ten parts of diluting fluid. Acetic acid, 
0.2 of one per cent., is usually employed for this purpose. 

5. The Percentage of Corpuscles and Plasma in Human Blood. 
Fill the two graduated capillary tubes of a hematocrite with blood drawn 
from the tip of your own finger, insert into the instrument, and centrifuge 
as rapidly as possible. The experiment must be performed within the time 
limit of clotting in order to be successful. The corpuscles will be thrown 
down and the percentage of plasma and corpuscles can be read off directly. 
Should one fail to fill the tube exactly full, then the percentage of plasma 
and corpuscles can be calculated from the proportion which each bears to 
the quantity in the tube. 

6. Estimation of the Percentage of Hemoglobin. The percentage 
of hemoglobin in a sample of blood can best be obtained by either the Dare 
or the Sahli hemoglobinometer. The principle of the Dare is given in the 
text. It rests on a comparison of the color of a drop of undiluted blood 
with a standard color scale when illuminated by candle light. Sterilize 
a lobe of the ear or finger tip, draw a drop of blood, bring the edge of the 
Ware blood pipette carefully against the blood drop, allowing it to flow 
between the plates. Place this in the instrument and examine either in a 
dark room or with the instrument turned toward a dark wall or paper. 

A sample of blood may be taken by a Miescher pipette diluted in the 
Miescher hemoglobinometer, and its percentage of hemoglobin computed. 
See text, page 140, for diagram of instrument and description of the 

Perhaps a more convenient and certainly a quicker method for deter- 
mining the percentage of hemoglobin is Talquist's hemoglobinometer. By 
this method a drop of blood is drawn directly on to absorbent-paper furnished 
with the instrument, and the resulting stain is compared directly with a paper 
color scale which is graduated in percentage. In this method the comparison 
is made in ordinary daylight, and because of its rapidity it is very convenient 
for clinical examinations, though it is less accurate. 



7. Reaction of Blood Plasma. Wet a piece of red litmus-paper in 
saturated magnesium sulphate solution, then touch one end of the strip with 
a drop of blood drawn from your finger under sterile conditions. After a 
few moments wash off the excess of corpuscles in neutral distilled water. 
The blue at the point of contact with the blood indicates alkalinity. 

8. The Specific Gravity of Blood. From standard mixtures of 
chloroform and benzol with specific gravity of i . 050, i . 060, and i . 070 make 
up a set of specific-gravity solutions of 1.050, 1.052, 1.054, etc., to 1.070. 
These standards may be kept in stoppered 4-dram vials, or in test-tubes. 
The specific gravity of blood is determined by inserting with a pipet a 
drop of freshly drawn blood into the middle of one of the solutions, say 
i .056. Since the blood does not mix with the chloroform and benzol, the 
drop will rise or sink according to its relative specific gravity. By a few 
trials one may quickly find a specific gravity in which the drop of blood 
floats without rising or sinking. This represents the specific gravity of the 
drop of blood. 

This method permits rapid clinical application and has proven of con- 
siderable interest in the hands of clinicians. 

9. The Isotonicity of Blood. The absorption or loss of water by the 
corpuscles of blood in solutions of other concentrations than that of 
blood plasma can be used as a 

means of determining the isoton- 
icity of blood. Make up a series 
of solutions of sodium chloride, 
varying by tenths, from 0.5 to 1.2 
per cent. Prepare a series of 
slides with vaselin rings and 
mount drops of human blood in 
drops of saline of 0.4, 0.6, 0.8, i, 
1.2 and 1.4 per cent., examine 
immediately then every ten min- 
utes under a high-power micro- 
scope. The corpuscles of some 
of the slides will swell up and 
may disintegrate, others will 
show crenation as in figure 126. 
In the isotonic solutions the cor- 
puscles will appear of their nor- 
mal size and condition. 

10. Coagulation of Blood. a. formal Clot. Anesthetize a dog, insert 
a cannula into the carotid or femoral artery, and draw samples of blood 
into two or three clean, dry test tubes. Draw one sample into a test- 
tube that has had its sides oiled. Note the exact time at which the blood 

FIG. 132. Microscopic View of Clot Showing 
Fibrin Network. 


was drawn into the test-tubes and set the test-tubes in a test-tube rack. 
Examine at intervals of 30 seconds by gently inclining the test tubes. 
Presently it will be noted that the blood becomes more viscous and does 
not flow freely up the sides of the test-tubes. Later the whole mass will 
become jelly-like and will retain the form of the test-tube. Note the time 
of the first slight change, and also when the clot becomes more perfect. 
The sample in the oiled test-tube will be found to clot more slowly. 

If the test-tubes of clotted blood are left standing for a day, the coagu- 
lum will become smaller in size and a transparent yellowish blood will make 
its appearance on the surface or between the sides of the clot and the test- 
tube wall. This fluid is the serum and it is squeezed out by the shrinking 
of the fibrin which holds the corpuscles in its meshes. 

b. The Time of Blood Clotting. The speed of clotting is measured more 
accurately by Cannon's coagulometer, see figure 108. A sample of blood is 
carefully drawn from an artery under conditions which insure fresh circulat- 
ing blood (Cannon and Mendenhall, American Journal of Physiology, Vol. 34, 
p. 225, for fuller details). This sample is inserted in the coagulometer and 
successive tests for coagulation made every 30 seconds. Even a thread or two 
of fibrin is indicated by the apparatus if the lever is accurately counterpoised. 

FIG. 1320. Successive tests of the coagulation of blood drawn from the femoral 
artery of an animal in uniform condition. The mark below the time record signi- 
fies when the sample was drawn. Time in 30 second intervals. (From Cannon and 

c. Microscopic Examination of the Process of Clotting. Take a drop of 
fresh blood from the tip of your finger under sterile conditions and mount 
on a microscopic slide in a few drops of salt solution, and examine immediately 
under the high power. Small threads of fibrin will presently be seen to form 
across the field, usually being most clearly obvious where fragments of 
white corpuscles are noted, see figures 107 and 132. The threads of fibrin 
become more apparent when stained with rosanilin. 

d. Whipped Blood. Draw a sample of blood into a glass tumbler, 
enough to fill it one-half or two-thirds full. Immediately begin vigorously 
stirring the blood with a bunch of stiff wires or a pencil, and keep it up until 
the time of clotting has passed, 5 or 10 minutes. In this instance the wires 
will break up and collect the fibrin as fast as it forms, and no firm mass will 
be produced. The remaining fluid is called whipped blood. The fibrin can 
be removed from the wires and washed in tap water until all the adherent 
red corpuscles are removed. This mass of fibrin is white, elastic, and com- 
posed of a network of thread-like fibers. It is these fibers extending 


through and through the mass of blood which makes it retain the form of 
the vessel when undisturbed clotting occurs. 

e. The Influence of Salt Solution on Blood Clotting. Add 2 cc.of saturated 
magnesium sulphate, i per cent, sodium oxalate, and 0.9 per cent, sodium 
chloride to each of three test-tubes. Draw into each test-tube 5 to 6 cc. of 
blood and immediately mix thoroughly and let stand. The magnesium 
and oxalate test-tubes will not coagulate even though -they stand for days, 
but the sodium-chloride blood will clot in a few minutes. 

The magnesium-sulphate blood will coagulate if diluted with a sufficient 
amount of distilled water or physiological saline solution. Make a series 
of dilutions and note when coagulation takes place. The sodium-oxalate 
blood will coagulate when a sufficient excess (of i per cent, solution) of 
calcium chloride is carefully added to neutralize the excess of sodium 
oxalate. Demonstrate these on a series of samples. 

If a quantity of magnesium or oxalate blood is secured and separated by 
a centrifuge or by letting stand for a sufficient time, a sample of uncoagulated 
plasma will be obtained. This sample will coagulate when it is treated as 
just described above for blood, showing that the antecedents of fibrin are 
found in the plasma. 

/. Action of Tissue Extracts on Coagulation. Wash out the blood of 
a small animal by circulating 0.9 per cent, saline through the arteries until 
the outflowing fluid from the veins is clear. Take an organ, the liver for 
example, grind it up in a sausage mill by running it through the mill two 
or three times, then extract with 0.9 per cent, physiological saline. The 
macerating mass should be shaken up at intervals, and may be kept from 
spoiling by adding an excess of chloroform or by keeping on ice. A few 
cubic centimeters of this fluid extract added to a sample of freshly drawn 
blood will very greatly hasten the rapidity of coagulation. This tissue ex- 
tract contains the thrombqplastin of Howell (Thrombokinase of Morawitz), 
and hastens the formation of thrombin from thrombogen. 

ii. The Chemistry of Blood Plasma (or Serum). The blood plasma 
contains all the chemical substances which are utilized by the tissues in 
their nutrition or which are thrown off by the tissues as a result of their 
activity. It is therefore a very complex mixture. The serum contains the 
same substances in the same proportion, with the exception of the antece- 
dents of fibrin. It may, therefore, be used as a substitute for plasma in 
most cases. 

a. Proteins of Plasma. There are three principal proteins in blood 
plasma: serum-albumin, serum-globulin, and fibrinogen. These may be 
isolated as follows: To a sample of blood plasma add an equal quantity of 
sodium-chloride solution that has been saturated at 40 C. A white floccu- 
lent precipitate of fibrinogen comes down. Filter off, and add to the filtrate 


an equal volume of saturated ammonium sulphate. A second heavier pre- 
cipitate of serum- globulin separates out. When this is separated, and crys- 
tals of ammonium sulphate are added to the filtrate to complete saturation 
at 40 C., a third precipitate of serum-albumin separates. 

Each of these precipitates may be redissolved and purified by reprecipi- 
tation and can be tested by the characteristic protein reactions, see page 
107, which they all give. 

b. Sugars of Blood Plasma or Serum. If a quantity of blood serum is 
diluted with about 5 to 10 times its volume of water, and the proteins are 
removed by slight acidulation with acetic acid and boiling and filtering, the 
filtrate will contain reducing sugar and the various salts of blood plasma. 
To a concentrated sample of the filtrate add Fehling's solution and boil. 
A reddish precipitate indicates the presence of reducing sugar. If this ex- 
periment is done quantitatively, about from o.i to 0.2 percent, of sugar will 
be found. The sugar may be separated from the serum by dialysis through 
collodian membranes. 

c. The Salts of Blood Plasma. The salts of blood plasma are tested 
best by evaporating some of the blood serum to dryness, and burning the 
residue to oxidize the organic matter and dissolving the ash in water. Test 
as follows: To a sample add i per cent, of silver nitrate; a white precipitate 
soluble in an excess of ammonia, but not soluble in nitric acid, indicates 

To a second sample add i per cent, barium chloride. If sulphates are 
present there will be a white precipitate which settles out quickly. 

Acidify a third sample with nitric acid and add ammonium molybdate 
and heat. A yellow precipitate indicates the presence of phosphates. 

To the fourth sample add an excess of strong ammonia and i per 
cent, ammonium oxalate, heat. A white precipitate indicates the presence 
of calcium. 

12. Blood Corpuscles. The characteristic substance in the composi- 
tion of the blood corpuscles is the pigment known as hemoglobin, and this is 
the only chemical factor that will be considered in these experiments. 

a. Hemoglobin Crystals. Take a sample of dog's blood, or if a centri- 
fuge is available separate and wash a sample of blood corpuscles, and 
mix with about three volumes of saturated ether water, or if blood is used 
dilute with two or three volumes of water and add about 10 per cent, by 
volume of pure ether and shake thoroughly. Crystals of oxyhemoglobin 
will be formed, and these can be mounted and examined with a microscope. 

b. Spectrum of Hemoglobin and its Compounds. 

i. Oxyhemoglobin. Dilute a sample of defibrinated blood with about 
ten volumes of distilled water. From this stock solution make five solutions 
all differing by 33^ per cent. Examine these with a direct-vision spectro- 
scope. Make a drawing showing the absorption spectrum of each sample 


as compared with the solar spectrum. Compared with the spectrum 
shown in the frontispiece. 

2. Hemoglobin. The oxygen can be driven out from the oxyhemoglobin 
by adding to the above samples a few drops of ammonium sulphide and 
gently warming. Re-examine with the direct- vision spectroscope and map 
as before. 

3. Carbon-monoxide Hemoglobin. Pass a stream of ordinary illumi- 
nating gas through the dilutions of hemoglobin. The carbon monoxide 
of the gas will form a compound with the hemoglobin, which now turns a 
bright scarlet color. When examined with the spectroscope, the absorp- 
tion bands are found to be very similar to those of oxyhemoglobin. How- 
ever, map the spectrum to the scale as usual. Add the reducing agent, 
warm, and shake vigorously and re-examine. It is very difficult to break up 
the combination of hemoglobin with carbon monoxide, hence the poisonous 
action of this gas. 


THE blood is contained in a system of closed vessels through which it is 
kept in circulation during the life of the individual. The energy to keep up 
this motion is supplied by the heart, which is a large muscular organ con- 
sisting of four great divisions, the right and left auricles and right and left 
ventricles. The right ventricle discharges its blood into the pulmonary 

FIG. 133. Diagram of the Circulation in an Animal with a Completely Separated 
Right and Left Ventricle and a Double Circulation. Ad, Right auricle receiving the 
superior and inferior venae cavae, Vcs and Vci; Dth, thoracic duct, the main trunk of the 
lymphatic system; Ad, right auricle; Vd, right ventricle; Ap, pulmonary artery; P, lung; 
Vp, pulmonary vein; As, left auricle; Vs, left ventricle; Ao, aorta; D, intestine; L, liver; 
Vp, portal vein;Z,-y, hepatic vein. (After Huxley.) 

artery, through which it passes to the lungs, returning through the pulmonary 
veins to the left auricle, and into the ventricle. From the left ventricle 
the blood is pumped into the great aorta, and through its branches distrib- 
uted to the entire body. The terminal arteries are continuous with the 
IT 166 


general capillaries of the body, and these in turn with the veins, which con- 
duct the blood back to the right side of the heart again. It will be seen, 
therefore, that the circulatory apparatus consists of two great divisions, the 
pulmonary and the systemic circulation. This arrangement is illustrated 
by the accompanying figure. A study of this figure will show that in certain 
regions of the systemic circulation there are two capillary beds between the 
main arteries and the main veins. This subordinate stream through the 
liver is called the portal circulation, and the similar arrangement existing 
in the kidney is called the renal circulation. This, in general, is the outline 
of the course of the blood in its circulation. 

To make a study of the various phenomena manifested in the physiology 
of the circulatory apparatus, it is obvious that we have to do with certain 
fundamental activities; first, the physiology of the pumping organ, the heart; 
second, the movement of the blood in the arteries, capillaries, and veins; 
third, the co-ordination of these various divisions of the apparatus through 
the nervous system. To understand this it will be necessary to have in 
mind in detail the anatomical structure of the apparatus itself. 


The Heart. The heart is contained in the chest or thorax, and lies 
between the right and left lungs, figure 134, enclosed in a membranous sac, 
the pericardium. The pericardium is made up of two distinct parts, an 
external fibrous membrane and an internal serous layer which not only 
lines the fibrous sac, but also is reflected on to the heart, which it completely 
invests. These form a closed sac, the cavity of which contains just enough 
pericardial fluid to lubricate the two surfaces, and thus to enable them to glide 
smoothly over e'ach other during the movements of the heart. The vessels 
passing in and out of the heart receive investments from this sac to a greater 
or less degree. 

The heart is situated in the chest behind the sternum and costal carti- 
lages, being placed obliquely from right to left. It is of pyramidal shape, 
with the apex pointing downward, outward, and toward the left, and the 
base backward, inward, and toward the right. The heart is suspended in 
the chest by the large vessels which proceed from its base, but, excepting 
at the base, the organ itself hangs free within the sac of the pericardium. 
The part which rests upon the diaphragm is flattened, and is known as the 
diaphragmatic surface, while the free upper part is called the sternocostal 

On examination of the external surface the division of the heart into parts 
which correspond to the chambers inside of it may be traced. A deep trans- 
verse groove, called the coronary sulcus, divides the auricles from the ventri- 
cles; and the anterior longitudinal sulcus runs between the ventricles, both in 

1 68 


front and in the back, separating the one from the other. The anterior groove 
is nearer the left margin, and the posterior nearer the right, as the front 
surface of the heart is made up chiefly of the right ventricle and the posterior 
surface of the left ventricle. The coronary vessels which supply the tissue 
of the heart with blood run in the furrows or sulci; also the nerves and lymph- 
atics, which are embedded in more or less fatty material, are found in this 

The Chambers of the Heart. The interior of the heart is divided by a 
longitudinal partition in such a manner as to form two chief chambers or 
cavities, the right and the left. Each of these chambers is again subdivided 
transversely into an upper and a lower portion, called, respectively, the auricle 

FIG. 134. Outline of Heart, Lungs, and Liver to Show their Relations to each other and to 
the Chest Wall. (Heusman and Fisher's "Anatomical Outlines.") 

and the ventricle, which freely communicate. The aperture of communica- 
tion, however, is guarded by valves so disposed as to allow blood to pass 
freely from the auricle into the ventricle, but not in the opposite direction. 
There are thus four cavities in the heart, the auricle and ventricle of one side 
being quite separate from those on the other, figure 135. 

The right auricle, the right part of the base of the heart as viewed from 
the front, is a thin-walled cavity of more or less quadrilateral shape, pro- 
longed at one corner into a tongue-shaped portion, the right auricular appen- 
dix, which slightly overlaps the exit of the aorta from the left ventricle. 

The interior of the auricle is smooth, being lined with the general lining 
membrane of the heart, the endocardium. The superior and inferior vena 
cavce open into the auricle. The opening of the inferior cava is protected 


1 69 

and partly covered by a membrane called the Eustachian valve. In the 
posterior wall of the auricle is a slight depression called the fossa ovalis, 
which corresponds to an opening between the right and left auricles, exist- 
ing in fetal life the foramen ovale. The foramen fails to close in many 
individuals. Statistics from observations of hearts from the dissecting 
rooms show as many as forty out of a hundred hearts with more or less 
open interauricular foramina. In the appendix are closely set elevations 
of the muscular tissue covered with endocardium, and on the anterior 

FIG. 135. The Right Auricle and Ventricle Opened and a Part of their Right and 
Anterior Walls Removed so as to Show their Interior, i, Superior vena cava; 2, inferior 
vena cava; 2', hepatic veins cut short; 3, right auricle; 3', placed in the fossa ovalis, below 
which is the Eustachian valve; 3", is placed close to the aperture of the coronary vein; 
f, t> placed in the auriculo-ventricular groove, where a narrow portion of the adjacent 
walls of the auricle and ventricle has been preserved; 4, 4, cavity of the right ventricle, 
the upper figure is immediately below the semilunar valves; 4', large columna carnea or 
musculus papillaris; 5, 5', 5", tricuspid valve; 6, placed in the interior of the pulmonary 
artery, a part of the anterior wall of that vessel having been removed and a narrow portion 
of it preserved at its commencement where the semilunar valves are attached; 7, concavity 
of the aortic arch, close to the cord of the ductus arteriosus; 8, ascending part or sinus of 
the arch covered at its commencement by the auricular appendix and pulmonary artery; 9, 
placed between the innominate and left carotid arteries; 10, appendix of the left auricle; 
n, II, outside of the left ventricle the lower figure near the apex. (Allen Thomson.) 

wall of the auricle are similar elevations arranged parallel to one another, 
called musculi pectinati. 


The right ventricle forms the right margin of the heart. It takes no 
part in the formation of the apex. On section its cavity is semilunar or 
crescentic, figure 135. Into it are two openings, the venous orifice at the 
base, and the arterial orifice of the pulmonary artery, also at the base but 
more to the left. The part of the ventricle leading to the pulmonary artery 
is called the conus arteriosus. Both orifices are guarded by valves, the 
former called the tricuspid and the latter the semilunar. In this ventricle 
are also the projections of the muscular tissue called the trabecula carnece. 

The left auricle is situated at the left and posterior part of the base of 
the heart. The left auricle is only slightly thicker than the right and its 
form and structure are the same as in the right. The left venous orifices 
are oval and a little smaller than those on the right side of the heart. There 
is a slight vestige of the foramen on the septum between the auricles. 

FIG. 136. Cross-section of a Completely Contracted Human Heart, at the Level of the 
Lower and Middle Thirds. (According to Krehl.) 

The left ventricle occupies the posterior and apical portion of the heart, 
and is connected directly with the great aorta. It is separated from the 
auricle by the bicuspid or mitral valve, and the opening into the great aorta 
is guarded by the semilunar valves. The walls of the left ventricle are two 
or three times as heavy as those of the right, and may be as much as half an 
inch in total thickness. 

The left ventricle is capable of containing 90 to 120 c.c. of blood. The 
capacity of the auricles is considerably less after death owing to their con- 
tracted condition. The whole heart is about 12 cm. long by 8 cm. at its 
greatest width, and 6 cm. in thickness. The average weight in the adult is 
about 300 grams. 

The walls of the heart are constructed almost entirely of layers of muscu- 
lar fibers; but a ring of connective tissue, to which some of the muscular 



fibers are attached, is inserted between each auricle and ventricle and forms 
the boundary of the venous opening. Fibrous tissue also exists at the 
origins of the pulmonary artery and aorta. The muscular fibers of each 
auricle are in part continuous with those of the others and in part separate; 
and the same holds true for the ventricles. The fibers of the auricles are, 

FIG. 137. FIG. 138. 

FIG. 137. Cardiac Muscle Cells, Showing their Form, Branches, Nuclei, and Striae. 
From the heart of a young rabbit. Magnified 425 diameters, a, Line of junction between 
the cells (intercellular cement) ; b, c, branches of the cells. (Schafer.) 

FIG. 138. Cardiac Muscle Cells of the Left Ventricle of a Child at Birth (full term), to 
show the form of the cells, their structural details, their relations to one another, and their 
general agreement with those of cold-blooded vertebrates. /4, Large cell with two nuclei; 
this cell has nearly the proportions of those of the adult; B, group of cells in their natural 
relation. At the right of the middle cell are two spaces or fissures, n, Nucleus. The 
transverse striations cross the nuclei in all the cells, and each nucleus possesses several 
nucleoli. (Gage.) 

however, quite separate from those of the ventricles. The bond of con- 
nection between the auricles and the ventricles is made by the Purkinje 
fibers, an embryonic muscular type of tissue composing the auriculo- 
ventricular strand in the septum called the bundle of His. 

The development of the heart shows that it is derived from an embry- 
onic tube, which in its growth becomes twisted upon itself and divided into 
the two main divisions that we know in the adult. Anatomical dissections 
have shown that the muscles of the ventricles form spiral sheaths extending 
from the base of the two ventricles in spiral bands toward the apex. These 
bands of muscle are wound about the surface of the ventricles in the right- 



to-left direction. At the apex they extend up into the deeper tissue. If 
the superficial muscles are dissected off, there is left a great central core of 
muscle, which is described by MacCallum as running more transversely 


FIG. 139. 

FIG. 140. 

FIG. 139. Diagram of the Course of the Superficial Muscle Layers Originating in the 
Right and Left Coronary Sulci and in the Posterior Half of the Tendon of the Conus. 
C, Anterior papillary muscle. (After MacCallum.) 

FIG. 140. Diagram of the Course of the Superficial Muscle Layers Originating in the 
Anterior Half of the Tendon of the Conus. A, Posterior papillary muscle; B, papillary 
muscle of the septum. (After MacCallum.) 

FIG. 141. 

FIG. 142. 

FIG. 141. Diagram of the Course of the Layer Superficial to the Deepest Layer of the 
Muscle of the Left Ventricle, which is shown in outline. The deepest layer is also shown. 
A, Posterior papillary muscle; B, papillary muscle of the septum. (After MacCallum.) 

FIG. 142. Diagram of a Layer still more Superficial to that Shown in Fig. 141, and 
Ending in the Anterior Papillary Muscle. The deeper layers are represented in dotted 
lines. A, Posterior papillary muscle; B, papillary muscle of septum; C, anterior papillary 
muscle. (After MacCallum.) 

around the wall of one ventricle, then through the septum and around the 
other in a reverse scroll, figure 141. 

The Valves of the Heart. The valves of the heart are arranged so 
that the blood can pass only in one direction. These are the tricuspid 


valve, between the right auricle and right ventricle, figure 135, and the semi- 
lunar valve of the pulmonary artery, the mitral valve between the left auricle 
and ventricle, and semilunar valve of the aorta. The bases of the tricuspid, 
figure 152, and mitral valves are attached to the walls of the venous orifices 
respectively. Their ventricular surfaces and borders are fastened by slender 
tendinous fibers, the chorda tendinece, to the internal surface of the walls 
of the ventricles at points which project into the ventricular cavity in the form 
of bundles or columns, the musculi papillares. 

The semilunar valves guard the orifices of the pulmonary artery and of 
the aorta. They are nearly alike on both sides of the heart, but the aortic 
valve is altogether thicker. Each valve consists of three parts which are 
of similunar shape, the convex margin of each being attached to a fibrous 
ring at the place of junction of the artery to the ventricle, and the concave 
or nearly straight border being free, so as to form a little pouch like a pocket, 
figure 151. In the center of each free edge of the valves which contains 
a fine cord of fibrous tissue is a small fibrous nodule, the corpus Arantii of 
the valves. 

The Arteries. The arterial system begins at the left ventricle in a 
single large trunk, the aorta, which, almost immediately after its origin, 
gives off in the thorax three large branches for the supply of the head, neck, 
and upper extremities; it then traverses the thorax and abdomen, giving 
off branches, some large and some small, for the supply of the various organs 
and tissues it passes on its way. In the abdomen it divides into two chief 
branches. The arterial branches, wherever given off, divide and subdivide 
until the caliber of each subdivision becomes very minute. These smallest 
arteries are called arterioles. These arterioles are continuous into the capil- 
laries. Arteries frequently communicate or anastomose with other arteries. 
The arterial branches are usually given off at an acute angle, and the areas 
of the branches of an artery generally exceed that of the parent trunk, and, 
as the distance from the origin is increased, the area of the combined 
branches is increased also. As regards the arterial system of the lungs, the 
pulmonary artery and its subdivisions, they are branched in much the same 
manner as the arteries belonging to the general systemic circulation. 

The walls of the arteries are composed of three principal coats, the ex- 
ternal, or tunica adventitia, the middle, or tunica media, and the internal, or 
tunica intima. The external coat, figures 143 and 144, a, the strongest and 
toughest part of the wall of the artery, is formed of areolar tissue, with which 
is mingled throughout a network of elastic fibers. The middle coat, figure 
144, m, is composed of both muscular and elastic fibers with a certain pro- 
portion or areolar tissue. In the larger arteries, its thickness is compara- 
tively as well as absolutely much greater than in the small arteries, consti- 
tuting, as it does, the greater part of the arterial wall. The muscular 
fibers are unstriped, figure 145, and are arranged, for the most part, trans- 


versely to the long axis of the artery, figure 143, w, while the elastic element, 
taking also a transverse direction, is disposed in the form of closely inter- 
woven and branching fibers intersecting in all parts the layers of muscular 
fiber. In arteries of various size there is a difference in the proportion of 
the muscular and elastic element, elastic tissue preponderating in the largest 
arteries and unstriped muscle in those of medium and small size. The 
arteries are quite elastic in both large and small vessels. The internal coat 
is formed by a layer of elastic tissue, called thefenestrated membrane of Henle. 
It is peculiar in its tendency to curl up when peeled off from the artery, and 

FIG. 143. 

FIG. 144. 

FIG. 145. 

FIG. 143. Minute Artery Viewed in Longitudinal Section, e, Nucleated endothelial 
membrane, with faint nuclei in lumen, looked at from above; i, thin elastic tunica intima; 
m, muscular coat or tunica media; a, tunica adventitia. (Klein and Noble Smith.) 

FIG. 144. Transverse Section through a Large Branch of the Inferior Mesenteric 
Artery of a Pig. e, Endothelial membrane; i, tunica elastica interna, no subendothelial 
layer is seen; m, muscular tunica media, containing only a few wavy elastic fibers; e, c, 
tunica elastica externa, dividing the media from the connective-tissue adventitia, a. Mag- 
nification, 350 diameters. (Klein and Noble Smith.) 

FIG. 145. Muscular Fiber Cells from Human Arteries. Magnified 350 diameters, 
a, Nucleus; B, a fiber cell treated with acetic acid. (Kolliker.) 

in the perforated and streaked appearance which it presents under the micro- 
scope. The inner surface of the artery is lined with a delicate layer of elon- 
gated endothelial cells which make it smooth and polished and furnish a 
nearly impermeable surface along which the blood may flow with the 
smallest possible amount of resistance from friction. 

Many of the arteries are accompanied by a plexus of vaso-motor nerves. 
In the smaller arteries these nerves consist of few fibers that form a delicate 
network over the walls of the vessels. Many fibers appear to end in the 
muscle cells of the arterioles in the proximity of the nuclei. 

The Capillaries. In all vascular textures, except some parts of the 
corpora cavernosa of the penis, of the uterine placenta, and of the spleen, 


the transmission of the blood from the minute branches of the arteries to the 
minute veins is effected through a network of capillaries. They may be 
seen in all minutely injected preparations. 

The point at which the arteries terminate and the capillaries commence 
cannot be exactly defined, for the transition is gradual. The capillaries 
maintain essentially the same diameter throughout. The meshes of the 

FIG. 146. Vein and Capillaries. Silver-nitrate and hematoxylin stain, to show outlines 
of endothelial cells and their nuclei. (Bailey.) 

network that they compose are more uniform in shape and size than those 
formed by the anastomoses of the minute arteries and veins. 

The walls of the capillaries are composed of a single layer of elongated 
or radiate, flattened and nucleated endothelial cells, so joined and dove- 
tailed together as to form a continuous transparent membrane, figure 146. 

FIG. 147. Network of Capillary Vessels of the Air Cells of the Horse's Lung 
Magnified, a, a, Capillaries proceeding from b, b, terminal branches of the pulmonary 
artery. (Frey.) 

Outside these cells in the larger capillaries there is a structureless supporting 
membrane on the inner surface of which they form a lining. 

The diameter of the capillary vessels varies somewhat in the different 
textures of the body, the most common size being about 12 micro millimeters, 
of an inch. Among the smallest may be mentioned those of the 

1 7 6 


brain and of the follicles of the mucous membrane of the intestines; among 
the largest, those of the skin and especially those of the medulla of the bones. 

The form of the capillary network differs in the different organs of the 
body, but is usually adjusted to the structural arrangement of the cells of 
any given organ. 

The capillary network is closest in the lungs and in the choroid coat of 
the eye. In the human liver the interspaces are of the same size, or even 

PIG. 148. Capillaries of Striated Muscular Tissue. From a cat. Magnified 300 diam- 
eters. A, Artery; V, vein. (Heitzmann.) 

smaller than the capillary vessels themselves. In the human lung the spaces 
are smaller than the vessels; in the human kidney and in the kidney of the 
dog the diameter of the injected capillaries, compared with that of the inter- 
spaces, is in the proportion of one to four, or one to three. The brain 
receives a very large quantity of blood; but its capillaries are very minute 
and are less numerous than in some other parts. In the mucous mem- 



branes, for example in the conjunctiva and in the cutis vera, the capillary 
vessels are much larger than in the brain and the interspaces narrower, 
namely, not more than three or four times wider than the vessels. In the 
periosteum and in the external coat of arteries the meshes are much larger, 
their width being about ten times that of the vessels. It may be held as a 
general rule that the more active the functions of an organ are, the more 
vascular it is. 

The Veins. The venous system begins in small vessels which are 
slightly larger than the capillaries from which they spring. These vessels 

FIG. 149. Transverse Section through a Small Artery and Vein of the Mucous Mem- 
brane of a Child's Epiglottis; the artery is thick-walled and the vein thin-walled. A, 
Artery; the letter is placed in the lumen of the vessel, e, Endothelial cells with nuclei 
clearly visible; these cells appear very thick from the contracted state of the vessel. Outside 
it a double wavy line marks the elastic tunica intima. m, Tunica media consisting of 
unstriped muscular fibers circularly arranged; their nuclei are well seen, a, Part of the 
tunica advent'tia, showing bundles of connective-tissue fiber in section, with the circular 
nuclei of the connective-tissue corpuscles. This coat gradually merges into the surrounding 
connective tissue. V, The lumen of the vein. The other letters indicate the same as in 
the artery. The muscular coat of the vein, m, is seen to be much thinner than that of the 
artery, "x 350. (Klein and Noble Smith.) 

are gathered up into larger and larger trunks until they terminate in the two 
venae cavse and the coronary vein which enter the right auricle, and in four 
pulmonary veins which enter the left auricle. The total capacity of the 
veins diminishes as they approach the heart; but their capacity exceeds by 
two or three times that of their corresponding arteries. The pulmonary 
veins, however, are an exception to this rule. The veins are found after 


death more or less collapsed and often contain blood. They are usually 
distributed in a superficial and a deep set which anastomose frequently 
in their course. 

The coats of veins bear a general resemblance to those of arteries, figure 
149. Thus, they possess outer, middle, and inner coats. The outer coat is 
of areolar tissue like that of the arteries, but is relatively thicker. In some 
veins it contains a few musclar longitudinal cells. The middle coat 
is considerably thinner than that of the arteries; it contains circular un- 
striped muscular fibers mingled with a large proportion of yellow elastic and 
white fibrous connective tissue. In the large veins near the heart the 
middle coat is replaced for some distance from the heart by circularly 
arranged striped muscular fibers continuous with those of the auricles. 
The internal coat of veins consists of a fenestrated membrane lined by 
endothelium. The fenestrated membrane may be absent in the smaller 

FIG. 150. A, Vein with valves open. B, vein with valves closed; stream of blood passing 
off by lateral channel. (Dalton.) 

The veins are supplied with valves in certain regions of the body, espe- 
cially in the arms and legs. The general construction of these valves is 
similar to that of the semilunar valves of the aorta and pulmonary artery 
already described. Their free margins are turned in the direction toward 
the heart, so as to prevent any movement of blood backward. They are 
commonly placed in pairs, at various distances in different veins. In the 
smaller veins single valves are often met with, and three or four are some- 
times placed together or near one another in the larger veins, such as in the 
subclavians at their junction with the jugular veins. During the period 
of their inaction, when the venous blood is flowing in its proper direction, 


they lie by the sides of the walls of the veins; but when in action they come 
together like valves of the arteries, figure 150. Their situation in the 
superficial veins of the forearm is readily discovered by pressing along its 
surface, in a direction opposite to the venous current, i.e., from the elbow 
toward the wrist, when little swellings, figure 150, B, will appear in the 
position of each pair of valves. 

Lymphatic spaces are present in the coats of both arteries and veins; 
but in the tunica adventitia or external coat of the large vessels they form 
a distinct plexus of more or less tubular vessels. In smaller vessels they 
appear as sinuses lined by endothelium. Sometimes, as in the arteries 
of the omentum, mesentery, and membranes of the brain, the pulmonary, 
hepatic, and splenic arteries, the spaces are continuous with vessels which 
distinctly ensheath them, perivascular lymphatic sheaths. Lymph channels 
are said to be present also in the tunica media. 


The heart's action in propelling the blood consists in the successive 
alternate contraction, systole, and relaxation, diastole, of the muscular walls 
of the auricles and the ventricles. This activity furnishes the power which 
keeps the blood moving through the arteries, capillaries, and veins. The 
heart in its activity is like a great force pump in that it injects a certain 
quantity of blood at each contraction into the great arteries. Owing to 
the interaction between this heart-beat and the peripheral resistance to the 
flow of blood, together with the elasticity of the vessels themselves, a high 
pressure in the arteries is maintained all the time. The heart's contrac- 
tions pumping against this high arterial tension, are sufficient to maintain 
a constant flow of blood through the capillaries, and therefore through the 
active tissues. 

The heart beats at an average rate of about 72 times per minute during 
life. Each successive contraction really begins in the great veins, the 
superior vena cava and extends over the auricles and ventricles in regular 
sequence. The contraction of each successive part is called its systole 
and the relaxation its diastole. The diastole covers the period of active 
relaxation of the muscle and the pause before beginning its next con- 
traction. Each muscular chamber of the heart may, therefore, be said 
to have its own systole and diastole. The whole series of events from the 
beginning of one contraction until the corresponding event in the next 
contraction is described as the cardiac cycle. 

Action of the Auricles. The description of the action of the heart 
may be commenced at that period in each cycle in which the whole heart is 
at rest. The heart is then in a passive state. The auricles are gradually 


filled with the blood flowing into them from the veins, and a portion of this 
blood passes at once through the auricles into the ventricles, the opening 
between the cavity of each auricle and that of its corresponding ventricle 
being free during the pause of the entire heart. The auricles, however, 
receive more blood than at once passes through them to the ventricles. 
Near the end of the pause they become passively distended. At this 
moment a contraction wave begins at the bases of the venae cavae and, run- 
ning down over the walls about the mouths of the veins, passes to the 
muscular walls. The contraction of the auricles, the right and left 
contracting at the same time, forces the blood into the ventricles. 

The contraction of the muscular walls at the mouths of the great veins 
and of the sinus region maintains a condition of constriction during the 
time of the auricular contraction. This hinders the reflux of blood from 
the auricles into the veins during the auricular systole. Any slight re- 
gurgitation from the right auricle is limited by the valves at the junction of 
the subclavian and internal jugular veins beyond which the blood cannot 
move backward, and by the coronary vein which is supplied with valve-like 
fold at its mouth. The force of the blood propelled by the auricle into the 
ventricle at each auricular systole is transmitted in all directions, but, 
being insufficient to open the semilunar valves, it is expended in distend- 
ing the walls of the ventricle. 

Action of the Ventricles. The dilatation of the ventricles which 
occurs during the latter part of the diastole of the auricles, is completed by 
the forcible injection of the contents of the latter. The ventricles, now 
distended with blood, immediately begin to contract. The tricuspid and 
mitral valves are closed by the initial reflux of blood, or possibly by the 
currents of blood formed by the sudden injection of the ventricles by the 
auricular contractions. The ventricular systole follows the auricular 
systole so closely that it seems continuous with it. As a result of the ventri- 
cular systole, sufficient pressure is produced on its contents to overcome the 
pressure against the semilunar valves of the aorta and the pulmonary 
artery, and the ventricles are then emptied completely. After the whole 
of the blood has been expelled from the ventricles, the walls remain con- 
tracted for a brief period. 

The form and position of the fleshy columns on the internal walls of the 
ventricles no doubt help to produce the obliteration of the ventricular 
cavities during contraction. The completeness of the closure may often 
be observed on making a transverse section of a heart shortly after death 
in any case in which rigor mortis is very marked, figure 136. In such a case 
only a central fissure may be discernible to the eye in the place of the 
cavity of each ventricle. The arrangement of the muscles of the heart, 
as described on page 171, is such as to expend the whole force of the 
contraction in diminishing the cavity of the ventricle, or, in other words, 
in expelling the contents of blood. 


On the conclusion of the systole the ventricular diastole begins. The 
muscular walls relax and, by virtue of their elasticity, a slight negative 
pressure may be set up. This negative or suctional pressure on the left 
side of the heart may be of importance in helping the pulmonary circula- 
tion. It is somewhat inconstant in appearance, but has been found to be 
equal to as much as 20 mm. of mercury, and is said to be quite independent 
of the aspiratory power of the thorax itself, which will be described in a 
later chapter. The ventricles now remain in a state of relaxation or rest 
until the next systole begins. 

The duration of the ventricular systole and the diastole has been variously 
estimated. A computation of the time of these two phases, for man, in 
figure 153, reproduced from Hiirthle, gives for the systole 0.38 of a second 
and for the diastole 0.4 of a second, with a total of o. 78 of a second. This 
is equivalent to a rate of 77 per minute. Variation in the time of the systole 
and the diastole of the ventricle falls chiefly on the pause of the diastole. 

The ventricles undergo little or no change of shape in the unopened chest. 
At the moment in the systole when the ventricles begin to discharge their 

Conus arteriosus 

Left posterior cusp of 
pulmonary valve 

Left posterior cusp of 
aortic valve 

Right coronary 

Anterior cusp of 
aortic valve 

Right posterior cusp 

Right (marginal) 

Posterior (septal) 

Posterior cusp of v -\,v ^ ^ \ M^M CUS P ^ tricuspid 

mitral valve ? : ' ValvC 

Left ventricle 

Right ventncle 

FIG. 151. The Bases of the Ventricles of the Heart, showing the auriculo-ventricular, 
aortic, and pulmonary orifices and their valves. (Cunningham.) 

contents into the aorta and pulmonary arteries, respectively, there is a sharp 
decrease in size of the ventricles. This decrease takes place in all 

Action of the Valves. The Tricuspid Valve. During the diastole 
of both auricles and ventricles blood flows directly through the auricles into 
the ventricles, the auricles during this period acting as continuations of the 
large veins which empty into them. At the end of the period the ventricle 


on each side has already been filled and distended by the pressure of blood 
from the veins. The systole of the auricle completes this filling and slightly 
overdistends the ventricle. When the force of the auricular contraction is 
spent, the ventricular walls rebound slightly toward their former position 
and in so doing exert some pressure upon the ventricular side of the tricuspid 
valve which floats the cusps upward toward the auricle. In this connection 
another force comes into play, viz., vortex or back currents resulting from 
the flow of the blood into the ventricle under the pressure of the auricular 
systole. These currents aid in floating the valve cusps into apposition. 
Thus the venous orifices of the ventricles are closed at the end of the auricular 
systole; i.e., the end of the ventricular diastole. The ventricular systole 
which follows simply serves to place the valves under greater tension thus 
closing them still more firmly. It should be recollected that the diminution 
in the breadth of the base of the heart in its transverse diameters during 

FIG. 152. The Tricuspid Valves of the Ox, Closed. Vertical section. (Krehl.) 

the ventricular systole is especially marked in the neighborhood of the 
venous orifices, and this aids in rendering the tricuspid valve competent to 
close the openings by greatly diminishing the diameter. The cusps of the 
valve meet not by their edges only, but by the opposed surfaces of their thin 
outer borders. The margins of the valve are still more secured in apposition 
with one another by the simultaneous contraction of the papillary muscles, 
whose tendinous chords have a special mode of attachment for this very 
object. They compensate for the shortening of the ventricular walls and 
thus prevent the valve cusps from being everted into the auricles, an event 
that does occur in certain valvular lesions. 


The actions of the tricuspid and mitral valves on the right and left sides 
of the heart are essentially the same. 

The Semilunar Valves. The commencement of the ventricular systole 
precedes the opening of the semilunar valve by a fraction of a second. The 
intraventricular pressure increases with the progress of the systole until 
there is a distinct increase over the arterial pressure, then the opening of 
the valves takes place at once. The valves remain open as long as this 
difference continues. When the diastole of the ventricles begins and the 
arterial blood pressure exceeds the intraventricular pressure, there is an 
initial reflux of blood toward the heart which closes the semilunar valve. 

The dilatation of the arteries is peculiarly adapted to bring this about. 
The lower borders of the semilunar valves are attached to the inner surface 
of the tendinous ring which bounds the orifice of the artery. The tissue of 
this ring is tough and inelastic and the valves are equally inextensible, 
being formed mainly of tough fibrous tissue with strong interwoven cords, 
the effect, therefore, of each propulsion of blood from the ventricle into the 
artery is to dilate the wall of the first portion of the artery and the three 
pouches behind the valve cusps while the free margins of the cusps are 
drawn inward toward the center. This position of the valves and arterial 
walls is maintained while the ventricle continues in contraction; but as it 
relaxes, and the dilated arterial walls recoil by their elasticity, the blood is 
forced backward toward the ventricles and onward in the course of the 
circulation. Part of the blood thus forced back lies in the pouches (sinuses 
of Valsalva) between the valve cusps and the arterial walls; and the cusps 
are pressed together till their thin lunated margins meet in three lines 
radiating from the center to the circumference of the artery, figure 151. 
The corpora Arantii at the middle of the free margins insure a more effec- 
tive closure. 

The Sounds of the Heart. When the ear is placed on the chest over 
the heart, two sounds may be heard at every beat. They follow in quick 
succession and are succeeded by a pause or period of silence. The first 
sound is dull and prolonged; its commencement coincides with the impulse 
of the heart against the chest wall, and just precedes the pulse at the wrist. 
The second sound is shorter and sharper, with a somewhat flapping char- 
acter. The periods of time occupied, respectively, by the two sounds 
taken together and by the pause between the second and the first are 
unequal. According to Foster, the interval of time between the beginning 
of the first sound and the second sound is 0.3 of a second, while between 
the second and the succeeding first it is nearly 0.5 of a second, see figures 
153, 154, and 167. The relative length of time occupied by each sound, as 
compared with the other, may be best appreciated by considering the 
different forces concerned in the production of the two sounds. In one 
case there is a strong, comparatively slow contraction of a large mass of 

1 84 


muscular fibers, urging forward a certain quantity of fluid against con- 
siderable resistance; while in the other it is a strong but shorter and sharper 
recoil of the elastic coat of the large arteries shorter because there is no 
resistance to the flapping back of the semilunar cusps as there was to their 
opening. The sounds may be expressed by the words lubb dub. The 
beginning of the first sound corresponds in time with the three coincident 
events, namely, the beginning of the contraction of the ventricles, the 
closure of the tricuspid and mitral valves, and the first part of the dilatation 
of the auricles. The sound continues through a somewhat longer interval 
than the second sound. The second sound, in point of time, immediately 

FIG. 153. Simultaneous Tracings of the Cardiac Impact, or Cardiogram (lower), and 
the Heart Tones (upper), of Man. The cross strokes at the beginning of the cardiac sound 
tracing and on the cardiogram mark the synchronous events. (Hiirthle.) 

follows the cessation of the ventricular contraction, and corresponds with 
the commencing dilatation of the ventricles and the opening of the semi- 
lunar and mitral valves, figure 154. 

The exact cause of the first sound of the heart is not absolutely known. 
Two factors probably enter into it. First, the vibration of the semilunar and 
mitral valves and of the chordae tendineae. Second, the vibration of the 

FIG. 154. Simultaneous Tracings of the Heart Tone and Pulse of the Carotid in the 
Dog. Ai and A 2, First and second sounds; P, pulse; S, time in tenths and fiftieths of a 
second. (Einthoven and Geluk.) 

muscular mass of the ventricles themselves. The same mechanical condi- 
tions produce equal tension on the ventricular muscle itself and, according 


to the second view this is sufficient to account for the first sound. Looking 
upon the contraction of the heart as a simple contraction and not as a series 
of contractions, or tetanus, it is at first sight difficult to see why there 
should be any muscular sound when the heart contracts. 

The cause of the second sound is more simple and definite than that of 
the first. It is entirely due to the vibration consequent on the sudden closure 
of the semilunar valves when they are pressed down across the orifices of 
the aorta and pulmonary artery. The influence of these valves in producing 
the sound was first demonstrated by Hope who experimented with the hearts 
of calves. In these experiments two delicate curved needles were inserted, 
one into the aorta and another into the pulmonary artery below the line of 
attachment of the semilunar valves. After being carried upward about 
half an inch the needles were brought out again through the coats of the 
respective vessels, so that in each vessel one valve was held back against 
the arterial walls. Upon applying the stethoscope to the vessels it was 
found that after such an operation the second sound had ceased to be audible. 

Tube to communicate 
with the tambour 


Ivory Tape to attach 

knob instrument to the chest 

FIG. 155. Cardiograph. (Sanderson's.) 

Disease of these valves, when sufficient to interfere with their efficient action, 
also demonstrates the same fact by modifying the second sound or destroying 
its distinctness. 

The Cardiac Impulse. The heart may be felt to beat with a slight 
shock or impulse against the walls of the chest at the level of the fifth inter- 
costal space on the left side. Its extent and character vary in different 
individuals, a factor of considerable clinical significance, and therefore es- 
pecially discussed in works on clinical diagnosis. The cause of the cardiac 
impulse has been variously described. It will be remembered that during 
the period which precedes the ventricular systole the relaxed heart rests 
quietly in the pericardial cavity and with its apex exerting no pressure 

1 86 


against the wall of the chest. When the ventricles contract, their walls 
suddenly become firm and tense. Being firmly attached to the base the 
effect of the movement is to press the hardened ventricle against the 

Screw to adjust the lever 

Writing lever Tambour Tube to the cardiograph 

FIG. 156. Marey's Tambour, to which the Movement of the Column of Air in the 
Cardiograph is Conducted by a Tube, and from which it is Communicated by the Lever 
to a Revolving Cylinder so that the tracing of the movement of the cardiac impulse is 

chest wall. The discharge of the contents of the ventricle into the curved 
aorta intensifies this pressure by its mechanical effect in tending to 
straighten the curve of that vessel and thus holds the ventricle in firm 
contact with the chest. It is this sudden pressure of the contracting 
heart against the chest wall that is felt on the outside. The impact or 

FIG. 157. Typical Cardiogram (upper trace) from the Dog. Taken simultaneously 
with the aortic pressure (middle) and intraventricular pressure (lower) tracings. Time 
in o.oi of a second. (Hiirthle.) 

shock is possibly more distinct because of the partial rotation of the 
whole heart toward the right and front along its long axis. The move- 
ment of the chest wall produced by the ventricular contraction against 
it may be registered by means of an instrument called the cardiograph; 


I8 7 

and the record or tracing, called a cardiogram, corresponds almost ex- 
actly with a tracing obtained by an instrument applied over the con- 
tracting ventricle itself. 

The cardiograph, figure 155, consists of a cup-shaped metal box over 
the open front of which is stretched an elastic india-rubber membrane upon 
which is fixed a small knob of hard wood or ivory. This knob, however, 
may be attached, as in the figure, to the side of the box by means of a 
spring, and may be made to act upon a metal disc attached to the elastic 

The knob is for application to the chest wall over the place of the 
greatest impulse of the heart. The box or tambour communicates by 
means of an air-tight tube with the 
interior of a second or recording tam- 
bour supplied with- a long and light 
writing lever figure 156. The shock 
of the heart's impulse being communi- 
cated to the ivory knob, and through 
it to the first tambour, the effect is, 
of course, at once transmitted by the 
column of air in the elastic tube to 
the interior of the second recording 
tambour, also closed, and through 
the elastic and movable disc of the 
latter to the writing lever which is 
adjusted to a registering apparatus. 
This latter generally consists of a 
cylinder or drum covered with smoked 
paper and revolves by clock-work 
with a definite velocity. The point 
of the lever writing upon the paper 
produces a tracing of the heart's im- 
pulse, a cardiogram. 

Endocardiac Pressure. The effect 
of the muscular contractions and 
relaxations of the walls of the heart 
during its systole and diastole is to 
produce changes of pressure on its 
content of blood. When this pressure 
is measured by the proper instrument 
it is found that the pressure in the 
left ventricle varies between wide ranges. With the beginning of the 
muscular contraction, the pressure rises till it slightly exceeds that of the 
pressure of the aorta, remains high for a brief interval of time, then slowly 

FlG. 158. Double Cardiac Sound 
for Simultaneous Registration of the 
Blood Pressure in the Right Auricle 
and Ventricle, or in the Aorta and 
Left Ventricle. (Hurthle.) 



and quietly decreases to less than that of atmospheric pressure. It 
remains low until the beginning of the next systole. For the right ven- 
tricle the events and variations are relatively the same. 

FIG. 159. Simultaneous Registration of Curves of the Left Intra ventricular Pressure 
(lower), the Aortic Pressure (middle), and the Cardiac Impact (upper). Time, o.oi of a 
second. (Hiirthle.) 








as $eb 



FIG. 1 60. Schematic Cardiogram I, and Intraventricular Pressure Curves II, from the 
Dog. The ventricular pressure curve of the descending type is represented by the dotted 
line. Pressure in millimeters of mercury, time in tenths of a second. (Hiirthle.) 

In order to determine the endocardiac pressure communication must 
be established with the cavities of the heart. This is accomplished by a 
tube known as a sound, which is introduced into the left ventricle by 
passing it down the common carotid artery, or into the right auricle and 


ventricle through the jugular vein. When a cardiac sound is introduced 
and connected with some form of pressure-recording apparatus, accurate 
tracings of the variations in pressure during the heart-beat are obtained. 
Chauveau and Marey recorded and measured with accuracy the 
variations of the endocardiac pressure and the comparative duration of 

FIG. 161. Apparatus of MM. Chauveau and Marey for Estimating the Variations of Endo- 
cardiac Pressure, and Production of the Impulse of the Heart. 

the contractions of the auricles and ventricles. They placed three small 
india-rubber air-bags or sounds in the interior, respectively, of the right 
auricle, the right ventricle, and in an intercostal space in front of the heart 
of living animals the horse. These bags were connected by means of 

FIG. 162. Tracings of i, Intra-auricular; 2, Intraventricular Pressures; and 3, of 
the Cardiac Impulse of the Heart. To be read from left to right. Obtained by Chauveau 
and Marey. 

long narrow tubes with three levers arranged one over the other in con- 
nection with a registering apparatus, figure 161. The synchronism of the 
impulse with the contraction of the ventricles is also well shown by 
means of the same apparatus, and the causes of the several vibrations of 
which it is really composed have been demonstrated. 


In the tracing, figure 162, the intervals between the vertical lines rep- 
resent periods of a tenth of a second. The parts on which any given vertical 
line falls represent simultaneous events. It will be seen that the contraction 
of the auricle, indicated by the marked curve at A in the first tracing, causes 
a slight increase of pressure in the ventricle which is shown at A ' in the second 
tracing, and produces also a slight impulse, which is indicated by A" in the 
third tracing. The closure of the semilunar valves causes a momentarily 
increased pressure in the ventricle at D', affects the pressure in the auricle D, 
and is also shown in the tracing of the cardiac impulse D". 

The large curve of the ventricular and the cardiac impulse tracings, 
between A' and D', and A" and D", are caused by the ventricular contrac- 
tion, while the smaller undulations, between B and C, B f and C', B" and C", 
are caused by the vibrations consequent on the tightening and closure of 
the tricuspid and mitral valves. 

FlG. 163. Apparatus for Recording the Endocardiac Pressure. (Rolleston.) 

It seems by no means certain that Marey's curves properly represent 
the variations in intraventricular pressure. Objection has been taken to 
his method of investigation : First, because his tambour arrangement does 
not admit of both positive and negative pressure being simultaneously re- 
corded; second, because the method is applicable only to large animals, 
such as a horse; third, because the intraventricular changes of pressure 



are communicated to the recording tambour by a long elastic column of air; 
and fourth, because the tambour arrangement has a tendency to record 
inertia vibrations. H. D. Rolleston, who has pointed out the above in> 
perfections of Marey's method, has reinvestigated the subject with a more 
suitable apparatus. 

The method adopted by Rolleston is as follows: 

A window is made in the chest of an anesthetized and curarized animal, and 
an appropriately curved glass cannula introduced through an opening in the 
auricular appendix. The cannula is then passed through the auriculo-ventric- 

FIG. 164. Endocardiac Pressure Curve from the Left Ventricle of the Dog The 
thorax was opened and a cannula introduced through the apex of the ventricle; the abscissa 
is the line of atmospheric pressure. G to D represents the ventricular contraction- from 
D to the next rise at G represents the ventricular diastole. The notch, at the top of 'which 
is F, is a post-ventricular rise in pressure from below that of the atmosphere and not a 
presystohc or auricular rise in pressure. 

ular orifice without causing any appreciable regurgitation into the auricle, 
or it may be introduced into the cavity of the right or left ventricle by an opening 
made in the apex of the heart. In some experiments the trocar is pushed through 
the chest wall into the ventricular cavity. His apparatus is filled with a solution 
of leech extract in 0.75 per cent, saline solution, or with a solution of sodium 
bicarbonate of specific gravity 1.083. 

FIG. 165. Curve with a Dicrotic Summit from the Left Ventricle; the Abscissa Shows the 

Atmospheric Pressure. 

The animals employed were chiefly dogs. The movement of the column of 
blood is communicated to the writing lever by means of a vulcanite piston which 
moves with little friction in a brass tube connected with a glass cannula by means 
of a short connecting tube. 

When the lower part of the tube, A, is placed in communication with one 



of the cavities of the heart, the movements of the piston are recorded by means 
of the lever, C. Attached to the lever is a section of a pulley, H, the axis of which 
coincides with that of the steel ribbon, ; while, firmly fixed to the piston, is 
the curved steel piston rod, /, from the top of which a strong silk thread, J, 
passes downward into the groove on the pulley. 

This thread, /, after being twisted several times around a small pin at the 
side of the lever, enters the groove in the pulley from above downward, and 
then passes to be fixed to the lower part of the curve on the piston rod as shown in 
the smaller figure. 

The movement of the lever, C, is controlled by the resistance to torsion of 
the steel ribbon, E, to the middle of which one end of the lever is securely fixed 
by a light screw clamp, F. At some distance from this clamp, the distance 
varying with the degree of resistance which it is desired to give to the move- 
ments of the lever, are two holders, G t G r , which securely clamp the steel 

As the torsion of a steel wire or strip follows Hooke's law, the torsion being 
proportional to the twisting force, the movements of the lever point are pro- 
portional to the force employed to twist the steel strip of ribbon in other 
words, to the pressures which act on the piston, B. To make it possible to 
record satisfactorily the very varying ventricular and auricular pressures, the 
resistance to torsion of a steel ribbon adapts itself very conveniently. 

This resistance can be varied in two ways, ist, by using one or more pieces 
of steel ribbon or by using strips of different thicknesses; or ad, by varying 
the distance between the holders, G, G', and the central part of the steel 
ribbon to which the lever is attached. 

FIG. 166. Hiirthle's Spring Manometer. A , Viewed from the side; B, viewed from the top. 

Rolleston's conclusions are: That there is no distinct and separate 
auricular contraction marked in the pressure curves obtained from the right 
or the left ventricle, the auricular and ventricular rises of pressure being 
merged into one continuous rise. He concludes that the tricuspid and 
mitral valves are closed before there is any great rise of pressure within the ven- 
tricle above that which results from the auricular systole, a, figure 165. The 



closure of the valve occurs probably in the lower third of the rise AB, figure 
165, and does not produce any notch or wave. It is shown that the semilunar 
valve opens at the point in the ventricular systole, situated at c, about or a 
little above the junction of the middle and upper thirds of the ascending line 
AB, and the closure about or a little before the shoulder, D, The figures 
show, finally, that the minimum pressure in the ventricle may fall below 
that of the atmosphere, but that the amount varies considerably. 

On the whole, the most satisfactory recording instrument for the measure- 
ment of endocardiac pressures is the membrane manometer devised by 
Hurthle. This instrument avoids mechanical errors in a most satisfactory 
manner. By simultaneous tracings of the pressure in the ventricle and in 
the aorta by Hiirthle's differential manometer, the exact moment of the 






FIG. 167. Diagrammatic Representation of the Events of the Cardiac Cycle. For 
events which occur in sequence, read in the direction of the curved arrow; for synchronous 
events, read from the center to the periphery in any direction. (Coleman.) 

opening and closing of the semilunar valve has been determined. By 
similar methods we have been able to fix synchronism between other events 
occurring during the beat. These we will summarize in the following section. 


Cardiac Cycle. The entire series of occurrences in a single heart- beat 
is called the cardiac cycle. If the condition of the heart is considered at that 
moment when its muscular walls are at rest it will be found that the tricuspid 
and mitral valves are open, that the blood is flowing from the great veins 
into the auricle and the ventricle, which form a continuous cavity, and 
that the pressure is about that of the atmosphere, but slowly rising. Now 
a wave of contraction begins at the sinus node and extends over the auri- 
cles, which immediately contract and discharge their blood into the ventri- 
cles, somewhat distending their walls. At this moment the ventricular 
systole begins, the tricuspid and mitral valves are closed, the flow of blood 
into the ventricles is checked, and the first heart sound is heard. The con- 
traction of the ventricles produces a rapidly rising pressure on the enclosed 
contents until the pressure exceeds that in the pulmonary artery (and 
aorta), the semilunar valves open, and the blood is discharged into the 
arteries. The ventricles ordinarily remain contracted for a brief moment 
after their contents are emptied. 

The ventricular diastole begins next. With the initial relaxation and 
the first slight fall of the intraventricular pressure below that of the aorta, 
the semilunar valves close and the second sound is heard. The relaxation 
rapidly proceeds and the intraventricular pressure drops to below atmos- 
pheric pressure, the auriculo- ventricular valves fall open, the blood that 
has been accumulating in the auricles flows into the ventricles and the 
whole heart is in the state of pause described as the point of beginning of 
the cycle. 

The duration of the cardiac cycle varies with the heart rate. With a 
rate of 75 per minute, the cardiac cycle will take o . 8 of a second. In round 
numbers the systole of the auricle takes o . i of a second with a diastole of 
0.7 of a second, o . 6 of which is in the pause or rest period. The ventricle 
requires about 0.3 of a second for the systole, 0.5 of a second for the dias- 
tole, with o . 2 to o . 3 of this for the pause. It is evident that the whole heart 
is at rest at the same instant for from o . i to o . 2 of a second. 

The relations of the cardiac sounds to the systole and the diastole have 
been graphically recorded by Hiirthle, figure 153, and by Einthoven and 
Geluk, figure 154. The former found that in a heart-beat lasting o. 76 of a 
second the interval of time between the beginning of the first and second 
sounds was 0.25 of a second, and that the sounds occur just at the begin- 
ning of the ventricular systole and diastole, respectively. 

During the cardiac cycle the ventricles are completely closed from the 
moment of the beginning of the ventricular systole until the pressure amounts 
to a little greater than the pressure in the corresponding arteries, which 
takes about 0.2 of a second. From the opening of the semilunar valves 
until the closure of those valves, about o . 15 of a second, the ventricular cavity 
is in open communication with the arteries. There is, during the diastole, 



a second moment of complete closure of the ventricles, from the time of the 
closing of the semilunar valves until the ventricular pressure falls below the 
auricular pressure which permits the tricuspid and mitral valves to open. 

The Force of the Cardiac Action. In estimating the amount of 
work done by a machine it is usual to express it in terms of work units. A 
convenient work unit for this purpose is the amount of energy required to 
lift a unit of weight, i.e., i gram or i kilogram, through a unit of height; i.e., 
i centimeter or i meter, the work required being i gramcentimeter for 
small units, and i kilogrammeter for large units, respectively. The 
average work done by the heart at each contraction can be readily com- 
puted by multiplying the weight of blood expelled by the ventricles by the 
height through which it would have to be lifted to overcome the resistance 
to its discharge from the cavities into the arteries. 

The quantity of blood expelled and the pressure of the arteries can only 
be estimated for man. But the computations from indirect observations 
on other mammals indicate that the quantity of blood discharged from 
each ventricle at a single contraction is from 80 to 100 c.c. The pressure 
of the aorta, see page 221, is an average of, say, 120 mm. of mercury, or 
126 cm. of blood. The pressure in the pulmonary artery is much less, say, 
30 mm. (20 to 40), of mercury or 40 cm. of blood. Collecting these facts, 
we have the following computation: 


column of 

Work in 

The left ventricle 

no C.C. 

156 cm. 


The right ventricle 

oo c.c. 

40 cm. 


Total . . 

00 C.C. 

240 cm. 


This computation shows that each heart-beat expends 17,640 gramcenti- 
meters (17.64 grammeters) of work. The amount of energy developed in 
the contractions of the auricles may be ignored in this calculation, which is 
at best only of relative value. Calculations based on the determinations of 
Vierordt, also other earlier determinations, give much higher figures than 
are presented here. 

The Properties of the Heart Muscle. It is evident that if we are 
to arrive at any adequate explanation of the action of the heart, one of the 
first questions that must be considered is, what are the fundamental 
properties of heart muscle as such? 


It has already been shown, page 62, that the muscular fibers of the 
heart differ in structure from skeletal muscle fibers on the one hand, and 
from unstriped muscle on the other, occupying an intermediate position 


FlG - '68. FlG> I69 . 

FIG. 168. The Heart of a Frog (Rana esculenta), from the Front. V, Ventricle; Ad 
?E k *? ' auricle; B, bulbus arteriosus, dividing into right and left aorte 

FIG. 169. The Heart of a Frog (Rana esculenta), from the Back. s. v., Sinus venosus 
opened; c. s. s., left vena cava superior; c. s. d., right vena cava superior; c. i., vena cava 
mfenor; y. p., vena pulmonales; A. d,, right auricle; A. s. left auricle; A. p., opening of 
communication between the right auricle and the sinus venosus. X 2^-3. (Ecker.) 

between the two varieties. The heart muscle, however, possesses a prop- 
erty which is not possessed by skeletal muscle, or by unstriped muscle 
to such a degree, namely, the property of contracting rhythmically. 

Rhythmicity. The property of rhythmic contraction is shown by the 
action of the heart within the body; its systole is followed by its diastole in 

FIG. 170. Automatic Contractions of Sinus Muscle from the Terrapin's Heart in 0.7 
per cent. Sodium Chloride. Time in minutes. (New figure by L. Frazier.) 

regular sequence throughout the life of the individual. The force and fre- 
quency of the systole may vary from time to time as occasion requires, but 
there is no interruption to the action of the normal heart or any interfer- 


ence with its rhythmical contractions. Further, in an animal rapidly bled 
to death, the heart continues to beat for a time, varying in duration with 
the kind of animal experimentally dealt with 


and depending on whether or not there is entire 

absence of blood within the heart chambers. 

Furthermore, if the heart of an animal be removed , .S 

from the body, it still continue its alternate sys- 

tolic and diastolic movements for a varying time. 

Thus we see the power of rhythmic contraction 

depends neither upon connection with the central 

nervous system nor yet upon the stimulation 

produced by the presence of blood within its 

chambers. Whether or not rhythmicity is a prop- 

erty of heart muscle, as such, was conclusively 

settled by Gaskell and by numerous later investi- ~ 

gators by a very simple experimental procedure. 

Gaskell cut thin strips of the apex of the ventricle ^^^^HH| 
of the terrapin, which is free from the nerve cells, 
at least nerve ganglia, and found that they con- ^1 
tracted rhythmically for hours. This experiment 

has become a classic one for the study of the .2 

cardiac muscular tissue. Strips of cardiac mus- 
cle cut from the auricle and from the contractile H 
walls of the venae cavae, or sinus venosus, of the ' 
terrapin also contract rhythmically. If the strips 
of muscle are kept moist with the same blood ^^^^_ , 
or serum, then the rhythm of the sinus is greater j~ if I 
than that of the auricle, and that of the auricle g ;| ' 
greater than that of the ventricle, a difference , .S 
that is based on a physiological differentiation 
of the tissue. The sinus muscle is also more _^_^^^^^^_ 
delicately responsive to stimuli than is the ven- M *o - 
tricular muscle; i.e., it is more irritable. - 

Porter first performed the more difficult ex- ^^^^^^^mm #-& 
periment of isolating a small disc of muscle from 

the ventricle of the dog, leaving only the delicate - . , J "Sis 

nutrient artery through which the muscle was 
fed with defibrinated blood. This isolated small \ j| ,\ 

piece of ventricle contracted vigorously for many t 

minutes. Moorhouse has recently shown that 

various portions of the auricle, the sinus, and .; .r S ^ 

the veins contract in good rhythm. They also ,,;--; 

respond to various drugs in a characteristic HHHEBHU 


fashion. We may safely conclude, therefore, that the mammalian heart 
muscle is also automatically rhythmic. 

Tonicity. Cardiac muscle is characterized by its maintaining a con- 
stant degree of partial contraction described as muscle tone, or tonicity. 

FIG. 172. Automatic Contractions of a Strip of Ventricular Muscle from the Apex 
of the Terrapin's Heart contracting in 0.7 per cent. Sodium Chloride; from + to + 0.03 
per cent. Potassium Chloride is added to the Sodium Chloride. The thythm is recovered 
very slowly when the muscle is returned to 0.7 per cent, sodium chloride. Time in 
minutes (upper) and seconds (lower stroke). (Watkins and Elliott.) 

This property is possessed by all parts of the heart. In the auricle, how- 
ever, and especially in the muscular walls of the sinus and veins, there is 
considerable variation in tonicity. Botazzi showed that in the auricle of 

FIG. 173. Automatic Contractions of a Strip of Ventricular Muscle from the Apex 
of the Terrapin's Heart, a, Contracting in 0.7 per cent, sodium chloride; b, when 0.03 
per cent, calcium chloride solution is added. Time in minutes. (Frazier.) 

the toad the variations of tone were wave-like and periodic, even though 
the auricle were contracting with its ordinary fundamental rhythm. 
Howell has published numerous experiments showing tone waves in auri- 
cular and sinus muscle of the terrapin, in which muscle there may or may 


not be occurring at the same time the ordinary fundamental rhythmic 
contractions, figure 170. 

Irritability of Heart Muscle. Mention was made above of the difference 
in irritability of heart muscle chosen from different parts of the heart. 
The irritability of the muscle of each part also varies during the different 
stages of the contraction. Experiment shows that the muscle is not irri- 
table to a stimulus applied at any time from the beginning of the contrac- 
tion until the summit of the contraction is reached. This is called the 
refractory period. From the summit, through the relaxation and succeed- 
ing pause, the irritability rapidly increases until the beginning of the 
next contraction. . Considering the automatically contracting muscle, the 
point in which the automatic contraction is released, i.e., begins, is the 
point of maximal irritability. It is the moment when the irritability is 
so great that the muscular equilibrium is no longer stable, and the physio- 
logical contraction results. 

The irritability of heart muscle is very sharply influenced by its condition 
of nutrition, especially by the inorganic salts present in the blood and lymph, 
see page 207. The salt content of the blood comprises about 0.7 per cent, 
sodium chloride, 0.03 per cent, potassium chloride, and 0.025 to 0.03 per 
cent, calcium (phosphate probably), as well as traces of other metal bases. 

FIG. 174. Refractory Period in the Ventricular Strip of the Terrapin. 

The heart muscle has been shown by numerous investigators to be delicately 
responsive to the proportions of these salts in the blood, or in any artificial 
solution which may be substituted for blood. If the rhythm is to be taken 
as an index of the irritability, then an increase of sodium and calcium salts 
increases the irritability (rhythm), while the influence of an increase in potas- 
sium is to depress the irritability. 

Cardiac Contractions Always Maximal. The heart muscle exhibits 
another property which distinguishes it from ordinary skeletal muscle, viz., 
the way in which it reacts to stimuli. The latter, Chapter XIII, reacts 
slightly to a stimulus little above the minimal, and with an increase of the 


strength of the stimulus will give contractions of increasing amplitude until 
the maximum contraction is reached. In the case of the heart-beats this is 
not so, since the minimal stimulus which has any effect is followed by the maxi- 
mum contraction; in other words, the weakest effectual stimulus brings out as 
great a contraction as the strongest. If a contraction is induced earlier than 
it would automatically occur, then the succeeding pause is longer; i.e., there 
is a compensatory pause. Also the contraction induced is smaller and the 
one following the compensatory pause is proportionately larger. This 
observation can easily be demonstrated on the heart strip, see figure 174, 
or on the whole ventricle of the frog, which was originally used by 

Nerve influence, nutrition, temperature, etc., will of course affect the 
extent of the contractions, but under a given set of conditions it is held that 
the contractions which occur are maximal for the particular set of nutri- 
tive and other conditions. This is more readily understood when taken in 
connection with the fact that when a contraction originates in a cardiac 
cell it is conducted throughout the continuity of all the cells of the mass. 

Theories of the Heart-beat. The cause of the rhythmic power of 
the heart as a whole has been the subject of much discussion and experi- 
mental observation. Two leading hypotheses have given inspiration to 
investigators, and now one, now the other theory has attracted followers 
as new facts have been discovered. These are known as the neurogenic 
theory and the myogenic theory, respectively, though neither is proven 

The heart has long been known to have the power of rhythmic contrac- 
tions after removal from the body and after all connection with the central 
nervous system has been destroyed. 

The heart can be taken entirely away from the body of an animal 
and kept beating rhythmically with ease. This is true for many inverte- 
brates and for all vertebrates examined including fishes, frogs, turtles, 
snakes, birds, and numerous mammals including man himself. It is 
only necessary to supply the heart through its local circulatory vessels 
with the proper nutritive fluid well aerated with oxygen and at the 
normal temperature of the animal from which the heart is taken. The 
question long debated is this. What initiates . these wonderfully persis- 
tent and regularly repeated contractions? 

If the frog's or terrapin's heart is removed from the body entire, it will 
continue to contract for many hours and even days, and the contractions 
have no apparent difference from the contractions of the heart before 
removal. The contractions will take place, as we have mentioned, without 
the presence of blood or other fluid within its chambers. Not only is this 
the case, but the auricles and ventricle may be cut off from the sinus, 
and all parts continue to pulsate. Further, the auricles may be divided 



from the ventricle with the same result. If the heart be divided lengthwise, 
its parts will continue to pulsate rhythmically. The ventricle remains 
comparatively quiet, contractions occurring at longer intervals, if at all. 
However, the isolated ventricle remains irritable so long as bathed in 
blood or in a balanced Ringer solution, and will contract upon receiving 
a slight stimulus. In fact, a single stimulus will often call forth a series of 
contractions of the ventricle. The frog's ventricle, when its muscular 

FIG. 175. Isolated Nerve Cells from the Frog's Heart. 7, Usual form; II, twin cell; C t 
capsule; A 7 ", nucleus; P, process. (From Ecker.) 

and nervous connections with the auricle are physiologically severed, as 
by crushing, will remain quiet when fed by its own blood, though it will 
contract rhythmically when fed with physiological salt solution. 

It is thus seen that the rhythmical movements of these parts of the 
heart appear to be more marked in the parts at the venous end of the 
organ, i.e., the sinus and auricle, and less marked in the ventricular end. 
Ventricular pieces contract when still connected with the auricles but do 
not readily contract in the ordinary condition even when irrigated with 
blood. These are regarded as facts peculiarly in favor of the view that 
the rhythm is inherent in the special nervous elements of the heart. 

This view which has long been known as the neurogenic theory, attri- 
butes the remarkable power of the heart to continue contractions after 
removal from the body, and presumably while in the body, to the presence 
of the collections of nerve cells within the walls of the heart itself. The 
local nervous mechanism in the frog consists of three chief groups of cells 
or ganglia. The first group is situated in the wall of the sinus venosus at 
the junction of the sinus with the right auricle, Remak's ganglion. The 
second group is placed near the junction between the auricles and ven- 
tricles, Bidder's ganglion. The third is in the septum between the auricles, 
wn Bezold's ganglion. Small ganglia have been described for the base of 
the ventricle, but no ganglia are present in the apical part of the ventricles, 
though isolated neurones have been found. The nerve cells of which 
these ganglia are composed are generally unipolar, seldom bipolar. Some- 


times two cells are said to exist in the same envelope, constituting the twin 
cells of Dogiel. The cells are large, and have very large round nuclei and 
nucleoli, figure 175. The neurogenic theory assumes that the periodic 
discharge of motor nerve impulses takes place from these neurones thus 
stimulating the musculature of the heart to rhythmic contractions. The 
stimuli start at the region of the sinus and are conducted over the heart 
in orderly sequence, but their origin in nerves is questioned. 

In the myogenic theory ,the heart's rhythmical contractions are 
explained as due to the inherent property of the cardiac muscle itself. 
Most convincing facts in support of this theory have been arrived at by a 
study of cardiac muscle, as such, and by studies on the whole heart, 
particularly by Gaskell's method of blocking. The term blocking is 
explained as follows: It will be remembered that under normal con- 
ditions the wave of the contractions in the heart starts at the sinus and 
travels down over the auricles to the ventricles. The irritability of the 
muscle and its power of rhythmic contractions is greatest in the sinus, less 
in the auricles, and least in the ventricles. By an arrangement of liga- 
tures or by a system of clamping, one part of the heart may be more or less 
isolated from any other portion. With such a clamp the contraction 
waves can be more or less completely interrupted in their passage from the 
sinus end of the heart past the clamp toward the ventricular end. If the 
clamp is complete, so as to interrupt the physiological continuity between 
the parts, then any contractions in the apical portion will be entirely 
independent of those in the sino-auricular portion. If the blocking is 
partial only, then the ventricular end of the heart ordinarily contracts 
in unison with the sino-auricular, although its rate may be as i to 2, 
i to 3, etc. In other words, only every second or every third sino-auricu- 
lar contraction will be able to pass the block to the ventricle. 

The effects of blocking are due to the interruption of muscle continuity 
rather than to nerve continuity. This is beautifully demonstrated by an 
experiment of zigzag cutting of the ventricle in the terrapin, since it cannot 
be supposed that any nerves would pass through the ventricular mass by 
such a zigzag course. In this experiment the contraction wave passes 
down over the muscle and around the end of the cuts until it reaches the 
apex. The apex muscle contracts in sequence with the auricle and 
successive pieces of the ventricle. If the zigzag cuts are made almost 
complete so as to reduce to a minimum the muscular tissue which bridges 
from one cut to the next, then it happens that occasional contractions will 
be unable to pass and the apex contracts after its preceding piece in the 
ratio of i to 2, or i to 3, etc., as described above Thus, division of 
the muscle has the same effect as partial clamping in the same position. 
These facts all point to a greater power of rhythmicity in the cardiac 
tissue nearer the venous end of the heart. This difference of rhythmicity 


is not due to the nerves of the heart, say the myogenists, but to the 
inherent property of the muscle itself. 

It was thought for a long time that in the mammal there was no mus- 
cular continuity between the auricles and ventricles to conduct the con- 
traction wave and that this was an insurmountable difficulty in the way of 
accepting the myogenic theory of the heart beat. In 1893 Kent described 
a bundle of muscle fibers arising in the wall of the right auricle and near the 
septum and running down into and forming a muscular connection with the 
ventricles. This bundle was also independently described by His, Jr., 
and generally bears his name. This band is called the auriculo- ventricu- 
lar bundle. 

It is now generally recognized that the early embryonic cardiac tissue 
undergoes differentiation in two directions. Out of one of these types 
of tissue there is produced the wellknown cardiac muscular tissue which 
makes up the mass of the auricles and the ventricles. Out of the other 
differentiation is produced the type of tissue which constitutes the auri- 
culo-ventricular conducting or bundle system. This conducting type 
of tissue is striated like the ordinary cardiac tissue but in general appear- 
ance is more embryonic in type. Its cells constitute what is known as the 
Purkinje fibers. The main bundle described by His, Jr., runs in the inter- 
ventricular septum somewhat lightly buried in the tissue beginning at the 
base of the auricle on the right side and running down through the inter- 
auricular tissue to the septum of the ventricles where it divides into a 
right and left branch. Strands of this tissue extend somewhat up into 
the auricles but are elaborately developed into a net work lying just under- 
neath the endothelium of the right and left ventricles. The branch- 
ing net work of these cells shades into and is continuous with cells of the 
ordinary cardiac type. Miss De Witt (1909) made an excellent model 
of this system which has become classic in the literature and is reproduced 
in figure 106. The bundle system contains two regions known as nodes, 
the sino-auricular node imbedded in the wall of the right auricle just in 
the angle where it is joined by the superior vena cava; and the auriculo- 
ventricular node, described first by Tawara, which lies in the upper end of 
the His bundle. The physiological differentiation of this tissue is in the 
direction of rhythm production and facilitated conduction. 

The demonstration of the auriculoventricular bundle has proven to be 
of the strongest support to the myogenic theory. Erlanger has shown, 
by an ingenious device for partially clamping this muscular band, that 
even the mammalian ventricle exhibits the phenomenon of heart block. 
The sequence of auricle and ventricle can be perfectly controlled by the 
degree of compression exerted by the clamp. In his experiments the 
ventricle contracts in unison with every auricular contraction, or only 
every second or every third, according to the degree of blocking. 



It was shown along ago (by Merunowicz in 1875) that the isolated apex 
of the ventricle of the frog remains quiet when filled with blood, but readily 
gives good rhythmic contractions in physiological saline and other artificial 
solutions. The inactivity in blood is not necessarily, therefore, due to 
nervous isolation from the ganglionated parts of the heart nor to the 
bundle system alone. Contractions occur in the small bits of ventricular 
muscle as isolated by Gaskell, and these may continue for hours. It is. 
well known also that the embryonic heart contracts rhythmically before 
nerve cells have reached the organ or even before any blood is formed, as 
shown in the embryos of certain fishes. 

FIG. 176. Stereoscopic photograph of a model of the atrioventricular nodal system, 
in the calf's heart. Viewed from behind. The auricular network is not shown. Should 
be examined through a stereoscope. (Lydia M. DeWitt.) 

The phenomena of heart block, the contractions of the ventricular apex 
when physiologically isolated from the parts of the heart which contain the 
ganglia, the behavior of isolated strips of the heart, especially of the ven- 
tricle and the rhythm of the embryonic heart are all held to be in favor of 
the myogenic theory. However, in light of recent developments we must 
find our explanation of the block phenomena as well as of other facts used 
in argument for the myogenic theory in the physiology of this 
differentiation from the embryonic muscle, namely, the bundle system. 


Whatever view one adopts of the heart's beat he has to explain not only 
the periodic origin of the rhythm but also to explain the orderly sequence 
of auricles and ventricles. Keith and Flack (1906) have ascribed the 
initial rhythm to a center or node, the sino-auricular node as given above. 
In the mammalian heart the normal beat under normal conditions is 



generated at this point and conduction proceeds in an orderly manner in all 
directions not only toward the ventricle but out over the atria and on to the 
veins themselves. These last points have been most carefully studied and 

FIG. 1760. Normal electrocardiogram of man, lead II. 

established by Lewis and a number of his associates. Tawara, Eyster and 

Meek, Wilson, Greene and Gilbert, and others have explained that under 

certain conditions rhythm may arise lower down in the conducting tissue, 

namely, at the auriculo-ventricular node or center or even as low as the 

bundle branch (Greene and Gilbert). In this case the conduction is from 

the point of rhythm production not 

only toward the ventricles which 

contract together in response to the 

stimulus reaching them from the 

auriculo-ventricular node, but con- 

duction is reversed toward the auri- 

cle leading to delay in the auricular 

contraction in comparsion with the 


It is obvious that the tissue of 
the bundle system is differentiated 
highly in the direction of rhythm 
production and of conductivity. 
When once the rhythm arises in the 
sino-auricular node the stimulus is 
conducted five to ten times more 
rapidly over the bundle system to 

FIG. 1766. The figure gives the times 
the nroner auricular tissue and to of be g mnin g contraction of the respective 

the larger ventricular mass than 

points measured in fractions of a second 
after the beginning of the R in lead II. The 


would be possible through the slower 

conducting cardiac muscle. This area and occurs latest near the base of the 
insures the contraction of the entire aorta - ( Lewis -) 

ventricular walls at more nearly the same instant than would otherwise 
be the case. In fact, the arrangement of muscle bands of the ventricle 



does not materially influence the spread of the conduction wave over 
the ventricular walls (Lewis) as was once supposed. The Purkinje system 
furnishes the shorter pathway. These facts have been demonstrated 






FIG. 176^. Transection of the dog's heart to show the spread of the conduction 
stimulus from the bundle to the different parts of the ventricular walls, and the delay 
in conduction through the walls by muscle paths. (Lewis.) 

by recording the time of arrival of the stimulus at different points 
on the ventricular wall, figure 176^. The companion figure, 176^, gives 
a schematic transection of the dog's heart to indicate the direction 

FIG. 177. The rate of different isolated strips of mammalian ventricle under 

the influence of changes of temperature. nodal strip, 

coronary strip, J^ temperature variation, time in minutes. Tempera- 

ture in degrees centigrade, rate in beats per ten seconds. (Moorehouse.) 

of spread of the stimulus from the inner surface into and through the 
muscle walls of the two ventricles. The delay in sequence between the 
auricles and ventricles is represented by this rate of conduction through 


the bundle system. It is approximately 0.16 seconds. The time at 
which the contraction stimulus arrives at different points on the ventri- 
cles, measured from the moment of the beginning; of the R wave is illus- 
trated in Figure 176^. 

This newer conception of the heart's differ- 

entiations gives to the true cardiac muscle a HHE! *i ~' 

position in energy production under the direct | : |* 

control of the conducting system for its coor- ^M 1 

dination. To the conducting system is rele- 
gated the function of stimulus production and 

a rapid distribution of the stimulus that still 1?: 

~ ~ 
preserves a mechanically efficient sequence. 

The function of the nerve elements by 

this view is neither to initiate rhythm pro- ; .- ; , -^ 

duction nor control the orderly sequence of ? 

the beats but to regulate the whole organ as 
regards its four main functions, namely, rhythm, 
conduction, energy production, and irritability. 
The details of this regulation are discussed 
later. ^llW^^^^^f^ Hv 

Relation of Rhythm to Nutrition. The 
whole heart, like the muscular parts of which 
it is composed, responds delicately to its con- 
dition of nutrition. In the frog and the turtle 

hearts the muscular fibers are brought in inti- ^ 

mate contact with the blood contained within r ? 

the cavities. In the mammalian heart, on the 


other hand, a distinct system of vessels, the r ^OT$^i? 

coronary vessels and the vessels of Thebesius, ;3S^^ ^P^ : ^ 

supply blood to the walls. If the heart is sup- ^Jjjt'V ^ 

plied with nutrient fluid similar to its normal >igjf ;. 

blood, and with proper aeration to insure plenty 

of oxygen, it contracts with a strong rhythm for 

many hours. This rhythm, however, responds 

quickly to changes in the composition of the '" ;; "c^ : fg "..- 

nutrient fluid. An abundant supply of oxygen :L " 

is absolutely necessary to the maintenance of 

rhythm in the mammalian heart, though the !p F : ?"-- .^B "c 

heart, especially a cold-blooded heart, will con- v j. ^x-. - : '.?,.* <i- 

tract for a time in an atmosphere of hydrogen. ^^^.^ ; ^ ^ K"" 1 

No doubt the organic constituents of blood are '^^fe^' %> 

very essential to the prolonged maintenance 

of rhythm in the heart, but the heart is not 

dependent on these ingredients for its stimulus 



production. The inorganic salts seem to be peculiarly closely related 
to the development and character of the cardiac rhythm, figures 171, 172, 
and 173. Both the cold-blooded heart and the mammalian heart respond 
very quickly to the influence of these salts. The details of this influence 
have been discussed on page 199. It is somewhat surprising, however, 
that the highly organized mammalian heart will contract rhythmically 
for hours on purely inorganic nutrient fluid, provided only that the oxygen 
be supplied in sufficient quantity and under high enough tension. The 
isolated mammalian heart also responds sharply to a change in the salt 
content of the perfusing solution. For example, addition of potassium 
chloride to a Locke solution slows or even suppresses the rate, as is shown 
in figure 178. 

Irregularities of Cardiac Rhythm. There are a number of cardiac 
irregularities in rhythm that are due to variations in irritability, con- 
ductivity, or other of the normal properties of the differentiated tissue of 
the heart itself. The phenomena of this type of most common occurrence 
are heart block, extra ventricular systoles, and auricular fibrillation. 

Heart Block. It occasionally happens that the heart rate becomes 
very slow, 30 or 40 a minute, and the rate does not vary much from this 

FIG. 178(1. An electrocardiogram, lead II, and auricular and ventricular muscle 
tracings, A and V taken simultaneously from the dog's heart. Two extra ventricular 
contractions are artificially produced by stimulation of the right ventricle. They 
show the characteristic right ventricular dominance. The first is taller because the P 
of the natural stimulus and the R of the artificial coincide. Time, fifths and twenty- 
fifths of a second. (Lewis.) 

low level. On careful examination it is found that the rate is ventricular 
only and that the auricle is contracting much faster. The latter may con- 
tract in multiples of the ventricular rate, 2-1, 3-1, or 4-1 rhythm in 
which case there is said to be partial block. Only every second, third, 
etc., contraction reaches the ventricle. Or the two rates may be wholly 
independent as in total block. 



The conducting bundle or path between the sino-auricular node where 
the normal beat arises and the auriculo-ventricular node is usually at 
fault in partial block. In complete block the independent ventricular 
beats start from a rhythmic center in the auriculo-ventricular node as a 
rule. But the. block may be in the His bundle itself in which case the 
rhythm production is low in the conducting system or even in the ven- 
tricular muscle. 

Extra Ventricular Systoles. When for any reason some portion of the 
ventricular complex becomes excessively irritable its rhythmicity may 
be so much increased that it starts an independent contraction before the 
normal ventricular stimulus reaches the muscle. This leads to a con- 
traction with the shortened period between beats and is called an extra- 
ventricular systole. As a rule there is a longer or compensatory pause 
following an extra systole after which the regular rhythm again becomes 
dominant. Most people of middle or old age experience occasional extra- 
systoles. In disease they may become frequent and troublesome but 
they are of no particular importance. 

Auricular Flutter and Fibrillation. A type of irregularity that is more 
common is that of an auricular rate far above the normal, i.e., 150 or even 
more a minute. These are due to hyperirritability of the auricle often 

FIG. i j8b. Electrocardiogram of auricular fibrillation. 

with an ectopic center of rhythm production. When such hearts are 
examined with the electrocardiograph or with the polygraph it becomes 
evident that, the auricle is contracting at a very much higher rate than the 
ventricle. The ventricle does not respond to every auricular contraction, 
i.e., in this kind of block the stimulus falls within the refractory period of 
the ventricles. Each auricular contraction is complete and the series is 
regular but the rate is above that which can be conducted to the ventricle. 
Auricular flutter is the term that describes this phenomenon. 

The auricular contractions are not always coordinated and com- 
plete. They sometimes begin in apparently many foci at once so that 
no rhythmic center controls the entire auricular muscle. Such contrac- 
tions are called fibrillation. In auricular fibrillation individual muscle 


cells may contract and relax at as high as 400 a minute. These con- 
tractions spread to the conducting bundle system at irregular intervals 
and the ventricle contracts at unevenly spaced intervals. The arterial 
pulse beats are also irregularly spaced, figure 1 786. When ventricular fibril- 
lation occurs it quickly produces death, but auricular fibrillation only 
reduces the efficiency of filling the ventricle. The physician controls 
auricular fibrillation by reducing the irritability of the auricle and the 
conductivity of the bundle system. 


The.heart is capable of automatic rhythmic movement, yet while in the 
body its beats are under the constant control of the central nervous system. 
The influence which is exerted by the central nervous system is of two 
kinds: first, in the direction of slowing or inhibiting the beats, and second, 

FIG. 1 79. Effect on the Heart Rate and on the Arterial Blood Pressure of Stimu- 
lating the Right Vagus of the Dog. Stimulus applied at the mark "on" and removed 
at "off." Pressure in millimeters of mercury shown by the scale to the left. Time in 
seconds. (Hill and Chilton.) 

in the direction of accelerating or augmenting the beats. The influence 
of the first kind is brought to bear upon the heart through the fibers of the 
pneumogastric or vagus nerves, and that of the second kind through the 
sympathetic nerves. 

The Inhibitory Nerves. It has long been known, indeed since the 
experiments of the Weber brothers in 1845, that stimulation of one or 


both vagi produces slowing of the rhythm of the heart. It has since been 
shown, in all of the higher vertebrate animals experimented with, that 
this is the normal reaction to vagus stimulation. Moreover, a section 
of one vagus, or at any rate of both vagi, produces acceleration of the 

FIG. 1 80. Tracing Showing Action of the Vagus on the Heart of the Terrapin. A ur, 
Auricular; vent, ventricular tracing. The part between words "on" and "off" indicates 
a period of vagus stimulation. The part of tracing to the left shows the regular contrac- 
tions before stimulation. During stimulation, and for some time after, the beats of the 
auricle and ventricle are arrested. After they commence again the auricle contracts 
weakly at first, but soon acquires a much greater amplitude. The ventricular contrac- 
tions that follow the first weak auricular contractions are maximal in the terrapin, but 
not so in the frog. See next figure. Time in seconds. (Carr.) 

pulse by breaking the pathway from the vagus center to the heart; 
stimulation of the distal or peripheral end of the divided nerve normally 
produces slowing or stopping of the heart beats, showing that the fibers 
are efferent and thus carry the nerve impulses toward the heart. 

FIG. 181 Tracing Showing Diminished Amplitude and Slowing of the Pulsations of 
the Auricle and Ventricle of the frog without Complete Stoppage during Stimulation of 
the Vagus. (Gaskell.) 

It appears that any kind of stimulus, either chemical, mechanical, elec- 
trical, or thermal, produces the same effect, but that of these the most 
potent is a rapidly interrupted induction current. A certain amount of 
confusion has arisen as to the effects of vagus stimulation in consequence 
of the fact that fibers of the sympathetic nerve run within the trunk of the 


vagus nerves of some animals, for example, the frog. Speaking generally, 
however, excitation of any part of the trunk of the vagus produces inhibi- 
tion, the stimulus being particularly potent if applied to the points where 
the nerves enter the substance of the heart at the situation of the sinus 
ganglia. The stimulus may be applied to either vagus with like effect. 
There are quantitative differences, however, between the right and left 
vagi. The right vagus usually has the greater effect on rhythm. 

The effect of the stimulation of the vagus is threefold to slow the rate, 
or even to bring the heart to a complete standstill, to produce a decrease 
in the amplitude, and to delay conduction through the bundle system. 
The slowing does not take place until after the lapse of a short latent 
period during which one or more contractions may occur. The stoppage 
may be due either to prolongation of the diastole or to diminution of the 
systole. Vagus stimulation inhibits the spontaneous beats of the heart 
only, it does not entirely suppress the irritability of the heart muscle, 
since mechanical stimulation may bring out a beat during the pause 
caused by vagus stimulation. The inhibition of the beats varies in 
duration according to the strength of the stimulus and the animal stimu- 
lated. The heart of the terrapin can be completely inhibited for hours 
with a strong stimulus. This phenomenon is shown in figure 180, which 
illustrates the action of the vagus on the terrapin's heart. 

The heart of a dog escapes from complete inhibition in a few seconds. 
When the beats reappear, the first few are usually feeble, after a time the 
contractions become more and more strong, and may soon exceed both in 
amplitude and frequency those which occurred before the application of 
the stimulus. If the stimulation is prolonged, the inhibition escapes 
to a slow rate, much under the normal rate. It is held there with some 
variations until the stimulus ceases. This is due to the fact that, in the 
dog at least, the stimulation reacts more strongly on rhythm production 
at the sino-auricular nodal center, holding it in check with a strength that 
does not inhibit the auriculo-ventricular nodal rhythm. The funda- 
mental rhythm of the latter center is at a slower rate. The escape is to the 
auriculo-ventricular nodal rhythm. 

The inhibitory fibers have their origin in nerve cells in the nucleus of 
the vagus, and of the glosso-pharyngeal, located in the floor of the fourth 
ventricle. These cells have not been exactly identified, but the center is 
called the cardio-inhibitory center. The center is a bilateral one and the 
fibers from it pass into the great vagus trunk to be distributed to the heart 
through superior and inferior cardiac branches which help to form the 
cardiac plexus. Within the heart the inhibitory fibers form synapses with 
cells whose axones reach the cardiac muscle cells. The cardiac-inhibitory 
center is in more or less constant tonic activity, and the tonic influence is 
eliminated when both nerves are cut, figure 182. 



Inhibitory Reflexes. The inhibitory center is influenced by afferent 
nerve impulses which may reach it from the heart itself by the depressor 
nerve, or from other parts of the body. These reflex stimulations of 
the vagus center are constantly occurring during our daily life and are 
the most potent factors in co-ordinations going on between the heart and 
the rest of the body. 

FIG. 182. Arterial Blood Pressure of the Dog, Showing the Effect on the Heart Rate 
of Cutting both Vagus Nerves as marked. The scale to the left shows the pressure in 
millimeters of mercury. Time in seconds. The momentary inhibition just before the 
nerves were cut is probably due to mechanical stimulation of the nerves. (Hill and 

The vagus trunk itself contains afferent fibers, the depressor nerves, 
that arise from sensory endothelia in the heart itself and in the aortic 
arch. These endings are stimulated by excessive mechanical pressure. - 
Their nerve impulses react on the vagal motor cells to produce reflex 
inhibition, hence the cardiac slowing that relieves the pressure that pro- 
duced the reflex. This reflex apparatus is one of the most interesting 
self protecting mechanisms in the mammalian body. 

Rhythmical alterations of the heart rate occur in association with the 
effects of the mechanical variations of pressure of the thorax on the heart 
and blood vessels. Apparently the cardio-inhibitory center is stimulated 
during the rise of blood pressure. The activity of the center produces a 
slower rate of the heart during expiration, shown in figure 243. This 
variation in heart rate disappears when the vagi are cut off from the 
center. The variations from this cause are called sinus arrhythmia in 
clinical literature. Such variations are purely physiological and normal 
in character. 

The Accelerator Nerves. The influence of the accelerator nerves 
distributed to the heart through the thoracic sympathetic, is the reverse 
of that of the vagus. Stimulation of the sympathetic, even of one side, 
produces acceleration of the rate of the heart-beats, augmentation of the 
amplitude, or force, and better or at least faster conduction through the 
nodal system according to certain observers. Section of the nerveproduces 



slowing. The action of the nerve is more properly termed augmentor. 
The sympathetic or augmentor differs from the vagus in several particulars. 
First, the stimulus required to produce any effect must be more powerful 
than is the case with vagus stimulation. Second, a longer time elapses 
before the effect is manifest. Third, the augmentation is followed by 
exhaustion, the beats becoming after a time feeble and less frequent. 

FIG. 183. Diagrammatic Representation of the Origin and Course of the Cardiac 
Nerves in the Dog, showing the Constituent Neurones. D 1-5, First to fifth dorsal spinal 
nerves. Inhibitory fibers in blue, accelerators in red. (Modified from Moret.) 

The fibers of the sympathetic system, which influence the heart-beat in 
the frog, leave the spinal cord by the anterior root of the third spinal 
nerve. They pass by the ramus communicans to the third sympathetic 
ganglion, thence to the second ganglion, the annulus or ansa (around the 
subclavian artery), through the first ganglion, and along the main trunk 
to the exit of the vagus from the cranium. There the two nerves join 


and run down to the heart within a common sheath, forming the vago- 
sympathetic trunk. Stimulation of the accelerators of the frog must be 
applied to the pathway before the fibers join the common trunk if uncom- 
plicated augmentation is to be secured. On stimulation of the mixed 
vago-sympathetic trunk inhibition ordinarily occurs at once. Augmentor 
effects come on only after the inhibition has disappeared, usually fifteen 
or twenty seconds later. If the vagal influence is first removed by a 
specific poison, atropine, then on stimulation pure augmentation results 
at once. This method applied to the frog is one of the most satisfactory 
methods of illustrating the different elements in cardiac augmentation. 

In the dog the augmentor fibers leave the cord by the anterior roots of 
the second and third dorsal nerves, and possibly also by the first, fourth, 
and fifth dorsal nerves. They pass by the rami communicantes to the gang- 
lion stellatum, or first thoracic ganglion, and around the ansa to the inferior 
cervical ganglion of the sympathetic. Fibers from the ansa or from the 
inferior cervical ganglion proceed to the heart, figure 183. The course of 
the augmentor fibers in the spinal cord is not so well known except that 
they originate in an augmentor center in the medulla. The circulation 
of venous blood appears to stimulate the augmentor center, and of highly 
oxygenated blood the inhibitory center. 

The accelerator center, like the inhibitory, is in constant tonic activity; 
and the cardiac acceleration on cutting the vagi, shown in figure 182, is in 
part to be ascribed to this tone. When both nerves are stimulated 
together, the resulting rate is the algebraic sum of the opposed influences, 
according to Hunt. The accelerator center is influenced by afferent 
impulses arising throughout the body, and these reflexes contribute to the 
general co-ordination of the chest with the activities of the body. 

In addition to direct and reflex stimulation, impulses passing down from 
the cerebrum may have a similar effect, psychic stimulation. 

Other Influences which Affect the Heart. A great variety of special 
conditions influence the heart's action in the normal body, conditions that 
are not discussed directly under any of the categories treated above. Of 
these may be mentioned the coronary circulation, temperature, mechanical 
tension, age. 

The Coronary Circulation. The contractions of the heart cannot long 
be maintained without a due supply of blood or other nutrient fluid. The 
nutrient fluid for the heart of man and the mammals is supplied from the 
coronary arteries and the vessels of Thebesius. The coronary arteries arise 
from the base of the aorta, where they receive the benefit of the highest 
arterial pressure. The coronary arteries are terminal arteries; that is, 
they do not permit the establishment of a collateral circulation when one 
of their branches is blocked. If the block be complete, that portion of the 
heart wall supplied by the branch dies. The immediate effect of the 


closure of a large coronary branch, in the dog, may be occasional and 
transient irregularity or arrest of the ventricular contractions preceded 
by irregularities in the force of the contractions and a diminution in the 
amount of work performed. The force, rather than the rate, of the ven- 
tricular contractions is closely dependent upon the blood supply to the 
coronary arteries. Porter and others have shown that the pressure in the 
coronary vessels follows closely the pressure in the aorta and that there is 
not, as formerly claimed, a closure of these vessels by the pressure of the 
systole of the ventricle. 

The vessels of Thebesius, which have been demonstrated to open both 
into the auricular and ventricular cavities, must now be looked upon, ac- 
cording to the investigations of Pratt, as an important source of cardiac 
nutrition. Blood may pass through them by way of connecting branches 
to the coronary arteries and veins. Pratt succeeded in maintaining cardiac 
contractions for several hours when the only source of nutrition was from 
these vessels. This source of nutrition may account for the survival of 
hearts for years where pronounced arterio- sclerosis of the coronary arteries 

Alteration of Temperature. The effect of cold is to slow the rate of the 
heart-beat. If the heart of a frog be cooled down to o C. it will stop 
beating, but when the temperature of the surrounding lymph or blood is 
again raised, it will renew its spontaneous beats. The effect of heat is to 
quicken and shorten the heart-beats, but at a moderate temperature, 20 
C., the contractions are increased in force, figure 177. 

The isolated mammalian heart is influenced by temperature variations 
in much the same way as that of the frog. It will contract slowly in a low 
temperature and rapidly in a temperature higher than that normal to the 
body. The very rapid heart in some high fevers is in part due to the increase 
in temperatures which affects the heart directly. 

Mechanical Tension. The mechanical factors produced by the heart- 
beat are so prominent that it would be surprising indeed if there were no 
reaction of these mechanical conditions on the heart itself. The isolated 
cardiac muscle responds very quickly to variations in tension. Beginning 
with a low tension the activity of heart muscle is increased up to a certain 
optimum tension, after which further increase is unfavorable to the develop- 
ment of automatic rhythm. A quite strong stretching will paralyze the 

Tension on the whole heart influences its activity, not only through the 
effects on the muscle, but indirectly through the nervous mechanism. High 
tension, such as contracting against a high aortic pressure, stimulates sensory 
nerves of the heart which, acting through the depressor nerve on the inhibi- 
tory center, produce reflex slowing of the heart. It also produces reflex 
vaso-dilatation. Both reflexes relieve the high tension on the heart. This 


nerve reaction takes place with a tension which still mechanically stimulates 
the cardiac-muscle substance, and the inhibitory effects must therefore over- 
come the direct stimulating effect of the tension on the muscle fibers. 

Age, Sex, etc. The average heart rate for the normal adult man is 72 
times a minute, but this rate will vary much in different individuals accord- 
ing to the age, sex, size, and personal equation. The frequency of the heart's 
action gradually diminishes from the commencement to near the end of life, 
but is said to increase again somewhat in extreme old age, thus: 

Before birth the average number of pulsations 

per minute is 1 50 

Just after birth 130 to 140 

During the first year 1 1 5 to 130 

During the second year 100 to 1 1 5 

During the third year 90 to 100 

About the seventh year 85 to 90 

About the fourteenth year 80 to 85 

In adult age. . 70 to 80 

In old age 60 to 70 

In decrepitude 65 to 75 

The heart rate is greater in woman than in man. It is also greater in 
small than in large individuals. The rate varies from the type in certain 
individuals where no cause can be assigned other than personal equation. 

Poisons and Other Chemical Substances. A large number of chemical 
substances have a distinct effect upon the cardiac contractions. Of these 
the most important are atropine, muscarine, digitalis, barium, nicotine, 
caffeine, etc. 

Atropine produces considerable augmentation of the heart-rate, and 
when acting upon the heart prevents inhibition by vagus stimulation. Its 
effects are produced by poisoning the nerve endings of the vagus within 
the heart. When these endings are poisoned stimuli arising in the inhibi- 
tory center of the medulla (tonic activity), or artificially applied to the 
vagus, cannot reach the heart muscle, and inhibition is impossible. 

Muscarine, which is obtained from various species of poisonous fungi, 
produces marked slowing of the heart-beats, and, in larger doses, stoppage 
of the heart. It produces an effect similar to that of prolonged vagus stimu- 
lation. The effect can be removed by the action of atropine, hence is 
supposed to stimulate the nerve endings of the vagus. 

Digitalis slows the heart by stimulating the vagi at their origin in the 
inhibitory center in the medulla. The heart muscle itself is also rendered 
more excitable. 

Veratrine and aconitine have a somewhat similar effect. 

Nicotine and caffeine are both very powerful cardiac stimulants. The 
great injurious effects of nicotine on the heart are due to two causes, first, 


to paralysis of the nervous mechanism and relative loss of control, 
second, to the great direct stimulation of the cardiac muscle. The 
constant overuse of tobacco, therefore, very sharply weakens the effi- 
ciency of the heart. Caffeine does not lead to so great disturbance of 

the heart's nutrition as does nicotine. 



Blood-Pressure. The subject of blood-pressure has been already 
incidentally mentioned more than once in the preceding pages; the time has 
now arrived for it to receive more detailed consideration. 

That the blood exercises pressure upon the walls of the vessels containing 
it is due to the following facts: 

The heart at each contraction forcibly injects a considerable amount of 
blood, 80 to 100 c.c., suddenly and quickly into the arteries. 

The arteries are highly distensible and stretch to accommodate the extra 
amount of blood forced into them. The arteries are already full of blood 
at the commencement of the ventricular systole, since there is not sufficient 
time between the heart-beats for the blood to pass into the veins. 

There is a distinct resistance interposed to the passage of the blood from 
the arteries into the veins by the enormous number of minute vessels, small 
arteries (arterioles) and capillaries, into which the main artery has been 
ultimately broken up. The sectional area of the capillaries is several hun- 
dred times that of the aorta, and the friction generated by the passage of 
the blood through these minute channels opposes a considerable hindrance 
or resistance in its course. The resistance thus set up is called peripheral 
resistance. The friction is greater in the arterioles, where the current is 
comparatively rapid, than in the capillaries, where it is slow. 

The interaction of these factors heart-beat, elastic vessels, and periph- 
eral resistance is sufficient to maintain a flow of blood through the entire 
circulatory system. It is the interrelation of these factors which main- 
tains an even and steady flow through the capillaries and past the tissues, 
where it is desirable that the conditions of blood flow should be most con- 
stant if the purposes of nutrition are to be best accomplished. In fact, 
we shall even find that it is the interaction of these same factors, together 
with the possibility of variations through regulation by their nerve-motor 
mechanisms, that we have the great variations and adjustments of blood- 
pressure, speed of flow, volume of flow, and the regulation of volume in 
particular parts of the body or local control. 

Arterial Blood -Pressure. That the blood exerts considerable pres- 
sure upon the arterial walls in keeping them in a stretched or distended 
condition may be readily shown by puncturing any artery. The blood is 
instantly projected with great force through the opening, and the jet rises 
to a considerable height, the exact level of which varies with the size of the 


artery experimented upon. If a large artery be punctured the blood may 
be projected upward for several feet, whereas if it is a small artery the jet 
does not rise so high. Another characteristic of the jet of blood from a cut 
artery, particularly well marked if the vessel be a large one and near the 
heart, is the intermittent character of the outflow. If the artery be cut 
across, the jet issues with force, chiefly from the central end. If there is 
considerable anastomosis of vessels in the neighborhood the jet from the 
peripheral end may be almost as forcible and as intermittent as that from 
the central end. The intermittent flow in the arteries due to the action 
of the heart, and which represents the systolic and diastolic alterations of 
blood-pressure, may be felt if the finger be placed upon a sufficiently 
superficial artery. The finger is apparently raised and lowered by the 
intermittent distention of the vessel occurring at each heart-beat. This 
intermittent distention of the artery is what is known as the pulse, to the 
further consideration of which we shall presently return, but we may say 
here that in the normal condition the pulse is a characteristic of the arterial, 
and is absent from the venous, flow. 

At the same time it must be recollected that in the veins also the blood 
exercises a pressure on the containing vessels, though it is small when 
compared with the arterial pressure. As might be expected, therefore, 
the blood is not expelled with so much force if a vein be punctured or cut. 
The flow from the cut vein is continuous and not intermittent, and the 
greater amount of blood comes from the peripheral and not from the 
central end, as is the case when an artery is severed. 

Methods of Measuring Arterial Blood -Pressure. The pressure in 
an artery may be measured by cutting the vessel and introducing into it a 
cannula and connecting the cannula with a tall vertical glass tube. When the 
blood in the vessel is released to the cannula, a column of blood will rise in the 
tube at once to the height that can be supported by thfe pressure in that par- 
ticular vessel. If the vessel be an artery, the blood will rise several feet, 
according to the distance of the vessel from the heart, and when the pressure 
has reached its highest point it will be seen to oscillate with the heart-beats. 
This experiment shows that the pressure which the blood exerts upon the 
walls of the containing artery equals the pressure of a column of blood of a 
certain height. In the case of the rabbit's carotid it is equal to 90 to 120 cm. 
of blood, or rather more than the same height of water. In the case of the 
vein, if a similar experiment be performed, blood will rise in the tube only 
for 8 or 10 cm. or less. 

The usual method of estimating the amount of blood-pressure differs 
somewhat from the foregoing simple experiment. Instead of a simple 
straight tube or glass manometer for measuring the pressure, a U-shaped tube 
containing mercury, the mercury manometer, is employed. The artery is 
connected with the manometer by means of the cannula inserted into the 
vessel as before, an arrangement being made whereby the cannula, tubes, etc., 


are first filled with a half -saturated solution of magnesium sulphate or other 
saline to prevent the clotting of blood when it is allowed to pass from the 
artery into the apparatus. The loss of blood is prevented during the 
preparation of the details of the experiment by a clamp or bull-dog for- 
ceps. The free end of the U-tube of mercury contains a very fine glass 
or metal rod with a bulb which floats upon the surface of the mercury 
and oscillates with the oscillations of the mercury. As soon as there is 
free communication between the artery and the tube of mercury, the blood 
rushes out and pushes before it the column of mercury. The mercury will 
therefore rise in the free limb of the tube, and will continue to do so until a 
point is reached which corresponds to the mean pressure of the blood-vessel 
used. The blood-pressure is thus communicated to the near limb of the 
column of mercury; and the depth to which the latter sinks, added to the 
height to which it rises in the other limb, the weight of the saline solution 
being subtracted, will give the height of the column of mercury which the 
blood-pressure balances. For the estimation of the amount of blood-pressure 
one can make direct readings at any given moment and no further apparatus 

FIG. 184. FIG. 185. 

FIG. 184. Arterial Cannula. T-form for convenience in washing out clots. 
FIG. 185. Ludwig's Mercury Manometer. The mercury which partially fills the 
tube supports a float in the form of a piston, nearly filling the tube; a wire is fixed to the 
float, and the writing style or pen is guided by passing through the brass cap of the 
manometer tube; the pressure is communicated to the mercury by means of a flexible 
metal tube filled with fluid. 

than this is necessary. But in the more accurate study of the variations 
of pressure in the arterial system, as well as its absolute amount, the instru- 
ment is usually combined with a recording apparatus, called a kymograph. 
Numerous forms of recording kymographs are to be had in the market. 
These instruments, while all constructed on the same principle, vary chiefly 
in the accuracy of their construction and convenience of their adjustments. 


The essential part of a recording kymograph consists of a uniformly 
revolving cylinder accurately centered and carrying a paper on which a record 
is made of the physiological change which is being studied. This cylinder 
or drum may be driven by a weight, clock spring, electric motor, or other 
mechanical device that insures uniformity of speed and which is capable of 
speed regulation. The cylinder is covered with glazed paper, blackened in 
the flame of a lamp, and the mercury manometer is so supported that its 
float, provided with a style, writes on the cylinder as it revolves. In some 
of the instruments, especially Ludwig's continuous paper kymograph, a 
long paper band is made to pass over the recording surface and the record 
itself is written by various devices carrying ink. 

There are also many ways in which the mercury manometer may be 
varied; in figure 185 is seen a form which is known as Ludwig's. In order 
to obviate the necessity of a large quantity of blood entering the tube of the 
apparatus and being lost to the animal, it is usual to have some arrangement 
by means of which the mercury may, previous to the experiment, be forced 


FIG. 186. Tracing of Normal Arterial Pressure in the Dog, Obtained with the 
Mercurial Manometer. The smaller undulations correspond with the heart-beats; the 
larger curves with the respiratory movements. Pressure is in millimeters of mercury as 
shown by the scale to the left. Time in seconds. 

up in the tube of the manometer to the pressure level corresponding to 
approximately the mean pressure of the artery experimented with, so that the 
writing style simply records the variations of the blood-pressure above and 
below the mean pressure. This is done by causing the anti-coagulant 
solution, generally a saturated solution of sodium carbonate or of 10 per 


cent, magnesium sulphate, to fill the apparatus from a bottle suspended at 
a height about that of the pressure to be measured, and capable of being 
raised or lowered as required for the purpose. 

The cannula inserted and tied into the artery may be of several different 
kinds. A glass T-tube with the end drawn out and cut so that it is oblique, 
and provided with a slightly constricted neck to prevent its coming out of 
the artery easily, is a very convenient form, figure 184. Of the two free 
ends of the T-cannula one is connected with the manometer, the other with 
the pressure bottle. The peripheral end of the cut artery is tied to obviate 
the escape of blood. By this means, the presssure communicated to the 
column of mercury is the forward, and not the lateral, pressure of blood, 
but there is very little if any difference. 

As soon as the experiment is begun, the writing float is seen to oscillate 
in a regular manner, and a curve of blood pressure is traced upon the smoked 
paper by the style (or, if a continuous roll of unsmoked paper be used, the 
trace is made by an inked pen) when a figure similar to figure 186 will be 
obtained. This indicates two main variations of the blood pressure. The 
smaller excursions of the lever correspond with the systole and diastole of the 
heart, and the larger curves correspond with the respirations, being called 
the respiratory undulations of blood-pressure, to which attention will be directed 

FIG. 187. Tracing of Normal Arterial Pressure Taken from the Rabbit with a Hurthle 
Manometer. The horizontal lines show zero pressure. Time in seconds. (Dreyer.) 

in the next chapter. Of course, the undulations spoken of are seen only in 
records of arterial blood-pressure. They are more clearly marked in the ar- 
teries nearer the heart than in those more remote. The amount of the 
pressure in the smaller arteries as well as the indication of the systolic rise 
of pressure is, comparatively speaking, small. 

In order to record the details of the undulations of arterial pressure, it is 
better for some purposes to use the Hurthle membrane manometer than the 
mercurial manometer. Two views of this instrument are shown in figure 166. 


The instrument consists of a hollow tube and cup covered with rubber sheet 
against which a disc supported by a metal spring is adjusted. The appara- 
tus is filled with fluid, the interior of which is connected with the artery by 
means of a metal tube and cannula. The pressure transmitted to the appa- 
ratus tends to stretch the rubber and bend the spring, and the movement thus 
produced is communicated by means of a lever to a writing style and so to 
a recording apparatus. This instrument obviates the errors which might 
be caused by the inertia of the mercury in the mercurial manometer; it alsa 
shows in more detail the variations of the blood pressure in the vessel during, 
and after each individual beat of the heart. 

As regards the actual amount of blood-pressure, from observations which 
have been made by means of the mercurial manometer, it has been found 
that the pressure of blood in the carotid of a rabbit is capable of supporting 
a column of 90 to 1 20 mm. of mercury ; in the dog i oo to 1 7 5 mm. ; in the horse 
152 to 200 mm.; and in man the pressure is estimated to be about the same 
as in the dog. To measure the absolute amount of this pressure in any 
artery multiply the area of its transverse section by the height of the column 
of mercury which is already known to be supported by the blood pressure 
in any part of the arterial system. The weight of a column of mercury thus 
found will represent the absolute pressure of the blood. Calculated in this 
way, the blood pressure in the human aorta is equal to i . 93 kilogrammeters; 
that in the aorta of the horse being 5 . 2 kilogrammeters; and that in the radial 
artery at the human wrist only o . 08 kilogrammeter. Supposing the muscu- 
lar power of the right ventricle to be one-fourth that of the left, absolute 
pressure in the pulmonary artery will be only 0.5 kilogrammeter. The 
amounts above stated represent the arterial tension at the time of the 
ventricular contraction. 

The arterial pressure is greatest at the beginning of the aorta, and de- 
creases toward the capillaries. It is greatest in the arteries at the period of 
the ventricular systole and least during the diastole. The blood-pressure 
gradually lessens as we proceed from the arteries near the heart to those 
more remote, and again from these to the capillaries, as it does also from 
the capillaries along the veins to the right auricle. 

Arterial Blood -Pressure Measurements in Man. A number of 
instruments have been devised for estimating blood-pressure in man for 
clinical purposes. Some of these, though excellent in principle, are too 
complicated for general use. The first simple and approximately accurate 
form of apparatus was that devised by Riva-Rocci in 1896. This has been 
modified and improved in minor points since, but the principles of the 
original instrument remain practically the same. 

In brief, the apparatus, figure 188, consists of an elastic tube ending in a 
rubber bag which can be adjusted about the arm, and a mercury man- 
ometer connected with this tube and also with some form of air pump 



used for inflating the tube about the arm and thus exerting pressure upon 
its blood-vessels. The elastic tube is covered by some inelastic tissue, usu- 
ally a leather cuff, in order that the inflation of the bag may cause the full 
increase of pressure to be exerted upon the encased arm. By inflating the 
bag until the pulse at the wrist just disappears, and reading the height of 
the column of mercury in the manometer, the maximum or systolic 
pressure is obtained in millimeters of mercury. If now the pressure on 
the arm is reduced until the widest oscillations of the mercury column 
are obtained, the lowest position of the mercury meniscus represents the 
diastolic pressure. 

The apparatus depends on the principle that an external pressure just 
equal to the maximal pressure within an artery will hold the vessel in the 
collapsed condition, a fact that has been proven for vessels that are exposed. 
An external pressure that will just equal the minimal or diastolic pressure 
will cause a complete collapse of a vessel during diastole and will allow a 
complete expansion of an artery to its maximal limits during the systolic 
period of pressure. In other words, the mercury of the manometer will 
oscillate to its maximal. If the pressure is reduced to a still lower point, it 

FIG. 188. Riva-Rocci Apparatus (schematic) for Determining Blood Pressure in Man. 

will not be sufficient to compress the artery completely, and the mercury 
oscillations will again become smaller. In applying the instrument to the 
brachial artery, one must, of course, deal with a vessel deeply buried in mus- 
cular and other tissues. These latter tissues probably consume a certain 



small percentage of the pressure, an error which may be ignored for all 
comparative purposes. 

Erlanger has perfected a form of sphygmomanometer which contains a 
very ingenious and compactly arranged recording device, figure 189. This 
instrument has a mercury manometer from which the pressures are read off 
directly. On a side limb of the manometer there is a rubber bag enclosed 
in a glass bell. The cavity of the bell outside of the rubber bag is connected 

FIG. 189. Erlanger's Sphygmomanometer, Shown with the Rubber Bag Attached to 
the Arm. The picture is taken at the end of an experiment after the pressure in the instru- 
ment is run up again to above the systolic pressure. The upper part of the cylinder shows 
a sphygmogram taken with the instrument. (Experiment and photo by Hill and Watkins.) 

with a recording tambour, the entire apparatus being fully supplied 
with the necessary valves and adjusting devices which make it 
mechanically very perfect. The instrument is mounted on a stand with a 
small clock and recording cylinder adapting it to convenient clinical use. 
The brachial arterial pressure of man when taken by this form of 
apparatus has been found to vary greatly, but Erlanger gives no mm. of 
mercury as the average of observations on young adults in the determi- 


nation of the systolic pressure; i.e., the maximal arterial pressure. He 
gives for the diastolic pressure 40 to 45 mm. of mercury below the systolic 
pressure. Other observers using the same method find a somewhat higher 
average pressure, see figure 190, which represents a fair type of observation. 
The form of sphygmomanometer in almost universal clinical and 
laboratory use for determining the arterial blood-pressure of man is the 
aneroid type of Dr. Rogers. This instrument or its various modifications 
measures the pressure by means of the expansion of an aneroid coupled 
with a mechanical lever and gage device. The most widely distributed 
forms of instruments of this type are known as the Tyco and Faught. 
These instruments use an arm belt and bag of the Riva-Rocci type. The 
rubber bag is inclosed in a cloth belt which is conveniently wrapped 
around the arm above the elbow. The bag contains two connections 

FIG. 190. Tracing taken with Erlanger's Sphygmomanometer. The figures indicate 
pressure in millimeters of mercury. Systolic pressure 160; diastolic pressure, 120. (New 
figure by Hill.) 

one of which is attached to the pressure gage, the other connected with 
a convenient pump made of either metal of rubber. The pressure meas- 
urement can be made directly from the oscillations of the dial as described 
for the Erlanger or Riva-Rocci apparatus. Readings may also be ob- 
tained by the palpation of the artery at the wrist as the pulse breaks 
through during gradual reduction of the pressure in the arm bag. How- 
ever, the most accurate determinations are made by the auscultatory 
method (Goodman and Howell). A Bowles sphygmometroscope, which is 
a stethoscope modified by a button attached to the center of the disc, is 
attached to the arm just below the arm band at the inner angle of the 
elbow with the button of the diaphragm directly over the brachial artery 
near its division into the ulnar and radial. 

In operation the arm band is pumped to a pressure above that of 
the underlying artery and then the pressure very gradually released. 
When the external pressure just equals to or is slightly less than the 
maximum pressure in the artery, some fluid will escape into the occluded 


limb of the artery below the band. The flow of this fluid produces a very 
definite first sound which is used to determine the moment of systolic 
pressure. The sounds in the brachial artery, known as Karatkoff sounds, 
have been described as going through five phases before the circulation is 
fully established in the cut off artery. The first phase is the initial 
development of a clear cut and sharp sound. It is the index of the 
systolic pressure. The first sound is followed by a series of murmurs 
called the second sound, and that by a more definite tone, the third phase. 
The third phase will vary in character with certain abnormalities in the 
vessel wall thickening, sclerosis, etc. 

The fourth phase is the appearance of a duller tone of diminishing 
intensity which rapidly fades into no sound, the so-called fifth phase. 
The fourth phase is taken as the index of minimal or diastolic arterial 

If the ascultatory reading and the palpation reading are made at the 
same time the latter usually gives a slightly lower systolic pressure than 
the former. In other words, the stethoscopic reading by the sound is the 
more accurate. The diastolic reading is far more accurately determined 
by the ascultatory method. Woley gives the average systolic pressure as 
127 mm. for all ages. But it is well known that the pressure increases 
with age from 75 at one year, to 105 in youth and 140 mm. or more at the 
age of fifty. 





Systolic Blood Pressure: 


120 to 135 

no to 133 

129 to 160 


105 to 127 

105 to 125 

118 to 150 

Diastolic Blood Pressure: 


68 to 90 

65 to 85 

70 to i 20 


65 to 75 

60 to 80 

70 to 98 

The Venous Blood-Pressure and Capillary Pressure. The blood- 
pressure in the veins is nowhere very great, but is greatest in the small veins, 
while in the large veins near the heart the pressure may become negative. 
In other words, when a vein is put in connection with a mercurial manom- 
eter the mercury may fall in the arm farthest away from the vein and will 
rise in the arm nearest the vein, the action being that of suction rather than 
pressure. In the large veins of the neck the tendency to suck in air is espe- 
cially marked, and is the cause of death in some accidents or operations 
in that region. The amount of pressure in the brachial vein is said to 



support 9 mm. of mercury, whereas the pressure in the veins of the neck 
may fall to a negative pressure of from 3 to 8 mm. 

The variations of venous pressure during systole and diastole of the 
heart are very slight, and a distinct pulse is never seen in veins except under 
extraordinary circumstances. In certain forms of cardiac valvular insuffi- 
ciency there may be considerable regurgitation of the blood with a strong 
venous pulse. 

Careful observations upon the web of the frog's foot, the tongue and 
mesentery of the frog, the tails of newts and small fishes, and upon the 
skin of the finger behind the nail (Hooker) ; as well as estimations of the 
amount of pressure required to empty the vessels of blood under various 
conditions, all indicate that the capillary blood- pressure is subject to very 
great variations. Apparently the variations follow the variations of 
pressure in the arteries, though the measurements of the capillary pressure 
of the skin in man indicate that it is occasionally markedly influenced by 
the venous pressure variations (Hough). In the skin in man it is from 30 
to 50 mm. mercury. 

The pulse in the arterioles, capillaries, and venules becomes more and 
more evident as the extravascular pressure is increased. The pressure in 
the web of the frog's foot has been found to be equal to about 14 to 20 mm. 
of mercury; in other capillary regions the pressure is found to be equal to 
from one-fifth to one-half of the ordinary arterial pressure. 

FIG. 191. Schema Showing the Relation between Blood Pressure, Velocity of Flow, 
and Vascular Area, in the Arteries, Capillaries, and Veins. Ordinates represent height 
of pressure and speed of flow. The abscissa, b-c, represents zero pressure and speed. 
Space between lines a-b and d-e represents arterial system; between d-e and/-g, capillary 
system, and between f-g and h-i, the venous system. Line A-B equals pressure; line C-D, 
speed of flow; and line E-F, vascular area. (Modified from Gad.) 

General Variations in Blood-Pressure. The arterial blood-pressure 
may be made to vary by alterations in either of the chief factors upon which 


the pressure in the vessels depends, but primarily by the cardiac contrac- 
tions and the peripheral resistance. Thus, increase of blood-pressure may 
be brought about by either, i, a more frequent or more forcible action of 
the heart, or 2, by an increase of the peripheral resistance. On the other 
hand, diminution of the blood-pressure may be produced, either by, a, a 
diminished force or frequency of the contractions of the heart, or by b, a 
diminished peripheral resistance. These different factors, however, al- 
though varying constantly, are so combined that the general arterial pressure 
remains fairly constant. For example, the heart may, by increased force or 
frequency of its contractions, distinctly increase the blood pressure, but this 
increased action is almost certainly followed by diminished peripheral re- 
sistance, and thus the two altered conditions may balance, with the result 
of bringing back the blood-pressure to what it was before the heart began 
to beat more rapidly or more forcibly. 

It will be clearly seen that the circulation of the blood within the blood- 
vessels must depend upon the diminution of the pressure from the heart 
to the capillaries, and from the capillaries to the veins, the blood flowing in 
the direction of least resistance. We shall presently see further that the 
local flow also depends upon the relations between the heart's action and 
the peripheral resistance both general and local. 

The Arterial Flow. The character of the flow of blood through the 
arterial system depends to a very considerable extent upon the structure 
of the arterial walls, and particularly upon the elastic tissue which is so highly 
developed in them. 

The elastic tissue of the arteries, first of all, guards them from the sud- 
denly exerted pressure to which they are subjected at each contraction of the 
ventricles. In every such contraction, as is above seen, the contents of the 
ventricles are forced into the arteries more quickly than they are discharged 
through the capillaries. The blood, therefore, being for an instant resisted 
in its onward course, a part of the force with which it is impelled is directed 
against the sides of the arteries; under this force their elastic walls dilate, 
stretching enough to receive the blood, and becoming more tense and more 
resisting as they stretch. Thus by yielding they break the shock of the 
force impelling the blood. On the subsidence of the pressure, should the 
ventricles cease contracting, the arteries are able by the same elasticity to 
resume their former caliber. 

The elastic tissue in the same way equalizes the current of blood by main- 
taining pressure on it in the arteries during the period at which the ventri- 
cles are at rest or are dilating. If the arteries were rigid tubes, the blood, 
instead of flowing as it does in a constant stream, would be propelled through 
the arterial system in a series of spurts corresponding in time to the ventric- 
ular contractions and with intervals of almost complete rest during the in- 
action of the ventricles. But in the actual condition of the vessels, the force 
of the successive contractions of the ventricles is expended partly in the 


direct propulsion of the blood and partly in the dilatation of the elastic ar- 
teries; and in the intervals between the contractions of the ventricles, the 
force of the recoil is employed in continuing the flow onward. Of course 
the pressure exercised is equally diffused in every direction, and the blood 
tends to move backward as well as onward. All movement backward, 
however, is prevented by the closure of the semilunar valves, which takes 
place at the very commencement of the recoil of the arterial walls. 

The Arterial Flow is Rhythmic. By the exercise of the elasticity 
of the arteries, all the force of the ventricles is expended upon the circulation. 
That part of the force which is used up or rendered potential in dilating the 
arteries is restored or made active or kinetic when they recoil. There is no 
loss of force, neither is there any gain; for the elastic walls of the artery can- 
not originate any force for the propulsion of the blood; they only restore 
that which they receive from the ventricles. 

Since the ventricular discharge is intermittent, there will be intermittent 
accessions of pressure, and therefore the flow of blood in the arteries will be 
periodically accelerated. The volume of blood discharged from a cut artery 
increases and decreases with the systole and diastole of the ventricles, or with 
the systolic and diastolic pressures of the arteries themselves, the maximal 
speed being at the moment of maximal systolic pressure, see page 228. 

The equalizing influence of the resistance of the successive arterial 
branches reacts so that at length the intermittent accelerations produced in 
the arterial flow by the discharge of the heart cease to be observable, and 
the jetting stream is converted into the continuous and even movement of 
the blood which characterizes the flow in the capillaries and veins. 
The resistance which is offered to the flow of the blood stream in these 
vessels is a necessary agent in the production of a continuous stream of 
blood in the smaller arteries and capillaries. Were there no greater ob- 
stacle to the escape of blood from the larger arteries than exists to its en- 
trance into them from the heart, the stream would be intermittent, 
notwithstanding the elasticity of the walls of the arteries. 

The muscular element of the middle coat co-operates with the elastic 
element in adapting the caliber of the vessels to the quantity of blood which 
they contain; for the amount of fluid in the blood-vessels varies quite con- 
siderably even from hour to hour, and can never be quite constant. Were 
the elastic tissue only present, the pressure exercised by the walls of the 
containing vessels on the contained blood would be sometimes very small and 
sometimes inordinately great. The presence of a muscular element, how- 
ever, provides for a certain uniformity in the amount of pressure exercised: 
the muscles are in constant action or tone, and it is by this adaptive, uniform, 
gentle muscular contraction that the normal tone of the blood-vessels is 
maintained. Deficiency of this tone is the cause of the soft and yielding 
arterial pulse, and the sluggish blood flow through the arterioles. 


2 3 I 

Incidentally it may be mentioned that the elastic and muscular contrac- 
tion of an artery may also be regarded as fulfilling a natural purpose when, 
the artery being cut, the sudden contraction at first limits, and then, in con- 
junction with the coagulating blood, completely arrests, the flow of blood. 
It is only in consequence of such contraction and coagulation that we are 
free from danger through even very slight wounds; for it is only when the 
artery is closed that the processes for the more permanent and secure pre- 
vention of bleeding are established. 

The Velocity of the Arterial Blood Flow. The velocity of the blood 
current at any given point in the various divisions of the circulatory system 
is inversely proportional to the united sectional area at that point. If the 
united sectional area of all the branches of a vessel were always the same 
as the area of the vessel from which they arise, and if the aggregate sectional 
area of the capillary vessels were equal to that of the aorta, the mean rapidity 
of the blood's motion in the small arteries and in the capillaries would be the 
same as in the aorta. If a similar correspondence of capacity existed in the 
veins there would be an equal correspondence in the rapidity of the circula- 
tion in them. But the volume of the arterial and venous systems may be 
represented by two truncated cones with their apices directed toward the 
heart; the area of their united bases, the sectional area of the capillaries, 
being about eight hundred times as great as that of the truncated apex rep- 
resenting the aorta. Thus the velocity of blood in the smallest arterioles 
and the capillaries is about one-eight-hundredth of that in the aorta. 

The velocity of the stream of blood is greatest in the neighborhood of 
the heart. The rate of movement is greatest during the ventricular systole 
and diminishes during the diastole. The rate of flow also decreases along 
the arterial system, becoming least in the parts of the system most distant 
from the heart. Chauveau has estimated the rapidity of the blood stream 
in the carotid of the horse at over 20 inches per second during the heart's 
systole, and nearly 6 inches during the diastole (520-150 mm.) see figure 191. 

The Capillary Flow. It is in the capillaries that the chief resistance 
is offered to the progress of the blood; for in them the friction of the blood 
is greatly increased by the enormous multiplication of the surface with which 
it is brought in contact. 

When the capillary circulation is examined in any transparent part of a 
full-grown living animal by means of the microscope, figures 193, 194, the 
blood is seen to flow with a constant equable motion ; the red blood corpus- 
cles moving along, mostly in single file, and bending in various ways to ac- 
commodate themselves to the tortuous course of the capillary, but 
instantly recovering their normal outline on reaching a wider vessel. 

At the circumference of the stream and adhering to the walls of the 
larger capillaries, but especially well marked in the small arteries and veins, 
there is a layer of plasma which appears to be motionless. The existence 


of this still layer, as it is termed, is inferred both from the general fact that 
such a one exists in all fine tubes traversed by fluid, and from what can be 
seen in watching the movements of the blood corpuscles. The red cor- 
puscles occupy the middle of the stream and move with comparative 
rapidity; the colorless corpuscles run much more slowly by the walls of the 
vessels; while next to the wall there is a transparent space in which the 
fluid appears to be at rest ; for if any of the corpuscles happen to be forced 
within it, they move more slowly than before, rolling lazily along the side 
of the vessel and often adhering to its wall, figure 194. Part of this slow 
movement of the colorless corpuscles and their occasional stoppage may be 


FIG. 193. Capillary Network from Human Pia Mater, Showing also an Arteriole in 
Optical Section"; and a Small Vein. X 350. A, Vein; B, arteriole; C, large capillary 
D, small capillaries. (Bailey.) 

due to their having a tendency to adhere to the walls of the vessels. Some- 
times, indeed, when the motion of the blood is not strong, many of the 
white corpuscles collect in a capillary vessel, and for a time entirely 
prevent the passage of the red corpuscles. 

When the peripheral resistance is greatly diminished by the dilatation 
of the small arteries and capillaries, so much blood passes on from the 
arteries into the capillaries at each stroke of the heart that there is not 
sufficient remaining in the arteries to distend them. Thus, the intermit- 
tent current of the ventricular systole is not always converted into a con- 
tinuous stream by the elasticity of the arteries before the capillaries are 
reached. The intermittency of the flow occurs both in capillaries and 
veins and a venous pulse is produced. The same phenomenon may occur 
when the arteries become rigid from disease, and when the beat of the 



heart is so slow or so feeble that the blood at each cardiac systole has time 
to pass on to the capillaries before the next stroke occurs. The amount of 
blood sent at each stroke is not sufficient properly to distend the elastic 

It was formerly supposed that the occurrence of any transudation 
from the interior of the capillaries into the midst of the surrounding tissues 
was confined, in the absence of injury, strictly to 
the fluid part of the blood; in other words, that 
the corpuscles could not escape from the circulating 
stream, unless the wall of the containing blood ves- 
sel was ruptured. It is true that the English 
physiologist Augustus Waller affirmed in 1846 that 
he had seen blood corpuscles, both red and white, 
pass bodily through the wall of the capillary vessel 
in which they were contained (thus confirming what 
had been stated a short time previously by Addi- 
son). He said that no opening could be seen 
before their escape and that none could be observed 
afterward, so rapidly was the part healed. But 
these observations did not attract much notice 
until the phenomenon of escape of the blood cor- 
puscles from the capillaries and minute veins, apart 
from mechanical injury, was rediscovered by Cohn- 
heim in 1867. 

Cohnheim's experiment demonstrating the pas- 
sage of the corpuscles through the wall of the blood 
vessel is performed in the following manner: A 
frog is curarized; that is to say, paralysis is pro- 
duced by injecting under the skin a minute quantity of the poison called 
curare. The abdomen is then opened, a portion of the small intestine is 
drawn out, and its transparent mesentery spread out under a microscope. 
After a variable time, occupied by dilatation following contraction of the 
minute vessels and the accompanying quickening of the blood stream, 
there ensues a retardation of the current and the red and white blood 
corpuscles begin to make their way through the capillaries and small veins. 

The white corpuscles pass through the capillary wall chiefly by the 
ameboid movement with which they are endowed. This migration 
occurs to a limited extent in health, but in inflammatory conditions is 
much increased. 

The process of diapedesis of the red corpuscles, which occurs under cir- 
cumstances of impeded venous circulation, and consequently increased 
blood pressure, resembles closely the migration of the leucocytes, with the 
exception that they are squeezed through the wall of the vessel, and do not, 
like the leucocytes, work their way through by ameboid movement. 

FIG. 194. A Large 
Capillaryfrom the Frog's 
Mesentery Eight Hours 
after Irritation had been 
set up, Showing Emi- 
gration of Leucocytes. 
a, Cells in the act of 
traversing the capillary 
wall; b, some already 
escaped. (Frey.) 


Various explanations of these remarkable phenomena have been 
suggested. It is no longer believed that pseudo-stomata between contigu- 
ous endothelial cells provide the means of escape for the blood corpuscles. 
The chief share in the process is probably due to mobility and con- 
traction of the parts concerned, both of the corpuscles and of the capillary 
wall itself. 

The Speed of the Blood in the Capillaries. The velocity of the blood 
through the capillaries must, of necessity, be largely influenced by that 
which occurs in the vessels on both sides of them, in the arteries and 
the veins. Their intermediate position causes them to respond at once to 
any alteration in the size or rate of the arterial or venous blood stream. 
Thus, the apparent contraction of the capillaries, on the application of 
certain irritating substances or during certain mental states, and their 
dilatation in blushing may be referred primarily to the corresponding 
action of the small arteries. 

The Measurement of Velocity in the Capillaries. The observation of 
Hales, E. H. Weber, and Valentin agree very closely as to the rate of the 
blood current in the capillaries of the frog. The mean of their estimates 
gives the velocity of the systemic capillary circulation at about 0.5 mm. per 
second. The velocity in the capillaries of warm-blooded animals is 
greater, in the dog 0.5 to 0.75 mm. per second. This may seem incon- 
sistent with the facts, which show that the whole circulation is accom- 
plished in about half a minute. But the whole length of capillary vessels, 
through which any given portion of blood has to pass, probably does not 
exceed 0.5 mm. Therefore the time required for each quantity of blood to 
traverse its own appointed portion of the general capillary system will 
scarcely amount to more than a second. This comparatively slow 
velocity is evidently favorable to the nutritive interchanges that go on 
through these thin-walled vessels between the blood within the capillaries 
and the outside active tissues. 

The Venous Flow. The blood current in the veins is maintained, 
a, primarily by the contractions of the left ventricle; but very effectual 
assistance to the flow is afforded, &, by the action of the muscles capable of 
pressing on the veins with valves, and c, by the aspiration of the thorax 
and possibly, d, by the aspiration of the heart itself. 

The effect of muscular pressure upon the circulation may be thus ex- 
plained: When pressure is applied to any part of a vein, and the current of 
blood in it is obstructed, the portion behind the seat of pressure becomes 
swollen and distended as far back as the next pair of valves, which are in 
consequence closed. Thus, whatever force is exercised by the external 
pressure of the muscles on the veins, is distributed partly in pressing the 
blood onward in the proper course of the circulation, and partly in pressing 
it backward and closing the valves behind. 


The circulation might lose as much as it gains by such an action if it 
were not for the numerous communications, or venous anastomoses. 
Owing to these anastomoses the closing up of the venous channel by the 
backward pressure is prevented from being any serious hindrance to the 
circulation, since the blood which is arrested in its onward course by the 
closed valves can at once pass through some anastomosing channel and 
proceed on its way by another vein. Thus the effect of muscular pressure 
upon veins which have valves is turned almost entirely to the advantage 
of the circulation. The pressure of the blood onward is all advantageous, 
and the pressure of the blood backward is prevented from being a hin- 
drance by the closure of the valves and by the anastomoses of the veins. 

The venous flow is also assisted by the aspiration of the thorax and to 
some extent by that of the heart, since at some time during every cardiac 
cycle the intra-auricular and intra-ventricular pressure falls below that of 
the atmosphere. This activity will be considered more fully in the chapter 
on Respiration. In this connection it may be said, however, that the pres- 
sure in the great veins falls during inspiration and rises during expiration. 

The Velocity in the Veins. The velocity of the blood is greater in the 
veins than in the capillaries, but less than in the arteries; this fact depend- 
ing upon the relative capacities of the arterial and venous systems. If 
an accurate estimate of the proportionate areas of arteries and the veins 
corresponding to them could be made, we might, from the velocity of the 
arterial current, calculate that of the venous. The usual estimation is that 
the capacity of the veins is about two or three times as great as that of the 
arteries, and that the velocity of the blood's motion is, therefore, about 
one-half or one-third as great in the veins as in the arteries, i.e., 200 mm. 
a second. The rate at which the blood moves in the smallest venules is 
only slightly greater than that in the capillaries, but the speed of flow 
gradually increases the nearer the vessel approaches to the heart. The 
total sectional area of the venous trunks, compared with that of the 
branches opening into them, becomes gradually smaller as the trunks 
advance toward the heart, figure 191. 

The Velocity of the Circulation as a Whole. It would appear that 
a portion of blood can traverse the entire course of the circulation, in the 
horse, in half a minute. Of course it would require longer to traverse 
the vessels of the most distant part of the extremities than to go through 
those of the neck, but taking an average length of the vessels to be 
traversed it may be concluded that half a minute represents the average 
rate. Stewart estimated that the circulation time in man is probably not 
less than twelve nor more than fifteen seconds. 

Satisfactory data for these estimates are afforded by the results of. expe- 
riments to ascertain the rapidity with which chemicals introduced into the 
blood are transmitted from one part of the vascular system to another. The 


time required for the passage of solutions of potassium ferrocyanide, mixed 
with the blood, from one jugular vein, through the right side of the heart, the 
pulmonary vessels, the left cavities of the heart, and the general circulation, 
to the jugular vein of the opposite side, varies from twenty to thirty seconds 
in the dog. The same substance is transmitted from the jugular vein to the 
great saphenous vein in twenty seconds; from the jugular vein to the mes- 
enteric artery in between fifteen and thirty seconds; to the facial artery, 
in one experiment, in between ten and fifteen seconds; in another experi- 
ment, in between twenty and twenty- five seconds; in its transit from the 
jugular vein to the metatarsal artery, it occupies between twenty and 
thirty seconds. The result is said to be nearly the same whatever the 
rate of the heart's action. In more recent methods some innocuous dye 
like methylene blue is used, since it permits the determination without 
the loss of blood, the change in color being visible through the walls of the 
blood vessels. 

Stewart has made most accurate measurements of the circulation time 
by the electrical- resistance method. Strong salt solutions injected into the 
jugular vein on one side when they reach the other jugular (or any other 
vessel) are instantly detected by a decrease in the electrical resistance through 
the vessel when it is laid between the poles of the proper conductivity 

In all these experiments it is assumed that the substance injected moves 
with the blood and at the same rate, and does not move from one part of 
the organs of circulation to another by diffusing itself through the blood or 
tissues more quickly than the blood moves. The assumption may be ac- 
cepted that the times above mentioned as occupied in the passage of the in- 
jected substances are the times in which the portion of blood itself is carried 
from one part to another of the vascular system. 

Another mode of estimating the general velocity of the circulating blood 
is by calculating it from the quantity of blood supposed to be contained in 
the body and from the quantity which can pass through the heart in each 
of its contractions. But the conclusions arrived at by this method are less 
satisfactory. For the total quantity of blood and the capacity of the cavities 
of the heart have as yet been only approximately ascertained. Still the most 
careful of the estimates thus made accord very nearly with those already 
mentioned; and it may be assumed that the blood may all pass through 
the heart in man in about thirty seconds or even less. 


The most characteristic feature of the arterial pressure and blood 
flow is its intermittency, and this intermittent flow is seen or felt as 
waves of change in diameter of the arteries, known as the Pulse. 



The pulse is generally described as a wave-like expansion of the artery 
produced by the injection of blood at each ventricular systole into the already 
full aorta. The force of the left ventricle is expended in pressing the blood 
forward and in dilating the aorta. With the injection of each new quantity 
of blood into the aorta there is a wave of dilatation which passes on, expand- 
ing the arteries as it goes, running as, it were, over the more slowly traveling 
blood contained in them, and producing the pulse as it proceeds. A sharp 
distinction must be made between the passage of the pulse wave along an 
artery and the rate of flow of the blood in the vessel. The pulse produced by 
any given beat of the heart is not felt at the same moment in all parts of the 
body. Thus, it can be felt in the carotid a short time before it is perceptible 
in the radial artery, and in this vessel before it occurs in the dorsal artery of 
the foot. Careful measurements of the intervals between the time of the 
pulse at the carotid and at the wrist shows that the delay in the beat is in 
proportion to the distance of the artery from the heart. The difference in 
time between the pulse of any two arteries probably never exceeds one-sixth to 
one-eighth of a second. The rate at which the pulse travels in the arteries 
is from five to ten meters per second. 

The distention of each artery increases both its length and its diameter. 
In their elongation the arteries change their form, the straight ones becoming 
slightly curved, and those already curved becoming more so; but they re- 
cover their previous form as well as their diameter when the ventricular 
contraction ceases, and their elastic walls recoil. The increase of their 
curves which accompanies the distention of arteries, and the succeeding 
recoil, may be well seen in the prominent temporal artery of an old person. 
In feeling the pulse, the finger cannot distinguish the sensation produced 
by the dilatation from that produced by the elongation and curving. That 
which it perceives most plainly, however, is the dilatation and return more 
or less to the cylindrical form, of the artery which has been partially flattened 
by the finger. 

The Sphygmograph. Much light has been thrown on what may 
be called the form of the pulse wave by an instrument called the sphygmo- 
graph, figures 195 and 196. The principle on which it acts will be seen 
on reference to the figures. 

A small button replaces the finger in the act of taking the pulse. This 
button is made to rest lightly on the artery the pulsations of which it is de- 
sired to investigate. The up-and-down movement of the button is com- 
municated to the lever, to the hinder end of which is attached a light spring. 
The spring is adjusted to the proper tension to follow the movements of the 
artery wall during the pulse wave. The sphygmograph is bound on the 
wrist while taking a record. 

It is evident that the beating of the pulse will cause an up-and-down 
movement of the lever, the pen of which will write the effect on a smoked 

2 3 8 


card moved by the clock-work of the instrument. 

Thus a tracing of the pulse is obtained, and in this way much more deli- 
cate changes can be seen than can be felt by the mere application of the finger. 

FIG. 195. Diagram of the Lever of the Sphygmograph. 

The principle of the sphygmometer of Roy and Adami is shown in the diagram, figure 

The apparatus consists of a box, a, which is moulded to fit over the end of the radius 
so as to bridge over the radial artery. Within this is a flexible bag, q, filled with water, 

FIG. 196. Dudgeon's Sphygmograph. 

and connected by a T-tube with a rubber bag, h, and mercurial manometer. The fluid 
in the box may be raised to any desired pressure, and may then be shut off by tap, c. 
At the upper part of the box is a circular opening, and resting upon b is a flat button, d, 
which by means of a short light rod, e, communicates the movement of b to the lever,/. 
At the axis of rotation of this lever is a spiral watch-spring, g, which can be tightened 
at will, so that the lever can be made to take a vertical position at any desired hydro- 
static pressure within the box. The movements of the lever are recorded upon a piece 
of blackened glazed paper made to move in a vertical direction past it. When in use, 
the box is fixed upon the wrist by an appropriate holder, and the pressure is raised to 


2 39 

any desired height to which the lever is adapted by tightening or slackening the spring ; 
the tap, c, is then closed. The pressure within the box acts in all directions, and is 
correctly indicated by the manometer. 

To manometer. 

FIG. 197. Diagrammatic Sectional Representation of the Sphygmometer. a, Box 
by which the portion of the artery is covered; &, thin- walled india-rubber bag filled with 
water, and communicating through tap, c, with the manometer and thick- walled rubber bag, 
h; d, piston connected by rod, e, with recording lever,/; g, spiral spring, attached to axis of 
lever, and by which the pressure in b, against the piston, d, is counterbalanced; k, skin and 
subcutaneous tissue; m, end of radius seen in section; n, radial artery seen in section. 
(Roy and Adami.) 

Sphygrnogram. The tracing of the pulse obtained by the use of the 
sphygmograph, called a sphymogram, differs somewhat according to the artery 
from which it is taken, but its general characters are much the same in all 
cases. It consists of a sudden upstroke, or anacrotic limb, figure 198, A, 
which is somewhat higher and more abrupt in the pulse of the carotid and of 
other arteries near the heart than in the radial and other arteries more re- 
mote; and a gradual decline or catacrotic limb, P, less abrupt, and taking a 
longer time than A. It is seldom, however, that the decline is an uninter- 
rupted fall; it is usually marked about half-way by a distinct notch, C-D 
the dicrotic notch, followed immediately by a second more or less marked 
ascent of the lever called the dicrotic wave, D. Not infrequently there is 
also at the beginning of the descent a slight wave previous to the dicrotic 
notch; this is called the pre-dicrotic wave, and in addition there may be one 
or more slight waves after the dicrotic, called post-dicrotic, E. The inter- 
ruptions in the downstroke are called the catacrotic waves to distinguish 
them from an interruption in the upstroke, called the anacrotic wave, which 
is sometimes met with. 


The explanation of these tracings present some difficulties, not, how- 
ever, as regards the two primary factors, viz., the upstroke and downstroke, 

FIG. 198. Diagram of Pulse Tracing. A, upstroke or anacrotic limb; P, downstroke or 
katacrotic limb; C, pre-dicrotic wave; D, dicrotic; E, post-dicrotic wave. 

because they are universally taken to mean the sudden injection of blood 
into the already distended arteries, and the gradual recovery of the arteries 
by their recoil. These points may be demonstrated on a system of elastic 
tubes, with a pump to inject water at regular intervals, just as well as on the 
radial artery, or on the arterial schema, a more complicated system of tubes 
in which the heart, the arteries, the capillaries, and veins are represented. 
If we place two or more sphygmographs upon such a system of tubes at in- 
creasing distances from the pump, we may demonstrate, first, that the rise 

FIG. 199. Sphygmogram from the Radial Artery Taken with Marey's Sphygmograph. 


of the lever commences earliest in that nearest the pump, and, second, that 
it is higher and more sudden. So in the arteries of the body the wave gradu- 
ally gets less and less as we approach the periphery of the arterial system, 
and it is lost in the capillaries. 

The origin of the secondary waves is to some extent a matter of uncer- 
tainty. The anacrotic wave occurs when the peripheral resistance is high; 
that is, when, for some time during the systole, the flow from the aorta toward 
the periphery is slower than the flow from the ventricle into the aorta. Thus 
it is seen in some cases of nephritis where the arteries are rigid and the periph- 
eral resistance is high. 

The dicrotic wave is the most important of the secondary waves, and 
has been the subject of much discussion. It is constantly present in pulse 
tracings, but varies in height. In point of time the dicrotic wave occurs 
immediately after the closure of the aortic semilunar valves. In certain 


2 4 I 

conditions, generally of disease, it becomes so marked as to be quite plain 
to the unaided finger. Such a pulse is called dicrotic. The generally ac- 
cepted explanation of the cause of the dicrotic wave is that it represents a 


FIG. 200. A , Normal Pulse Tracing from Radial of Healthy Adult Obtained by the 
Sphygmometer; B, from same artery, with the same extra-arterial pressure, taken during 
acute nasal catarrh. 1-2 Anacrotic limb; 2-8 Catacrotic limb; 3 Predicrotic notch; 
5 Dicrotic crest; 6 Postdicrotic notch; 7 Postcrotic crest; 4 Dicrotic notch. 

rebound of the overdistended artery at the time of the closure of the aortic 
valves. During systole, as the blood is forcibly injected into the aorta, 
there is an overdistention of the artery. The systole suddenly ends, the 
aorta by reason of its elasticity tends to recover itself, the blood is driven 
back against the semilunar valves, closing them and at the same time giv- 
ing rise to a wave, the dicrotic wave, which begins at the heart and travels 
onward toward the periphery like the primary wave. According to Foster, 
the conditions favoring the development of dicrotism are: i, a highly ex- 
tensible and elastic arterial wall; 2, a comparatively low mean blood-press- 
ure, leaving the extensible reaction free scope to act; 3, a vigorous and rapid 
stroke of the ventricle discharging into the aorta a considerable quantity 
of blood. The other secondary waves are probably due to the oscillations 
in the elastic recoil of the arteries, though some of them at least may be 
due to the inertia of the instruments used. 

In the use of the sphygmograph care must be taken in the regulation of 
the pressure of the spring. If the pressure be too great, the characters of 
the pulse may be almost entirely obscured or the artery may be completely 
obstructed and no tracing is obtained. On the other hand, if the pres- 


sure is too slight, a very small part of the characters may be represented on 
the tracing. 


The flow of blood through the circulatory system depends on the inter- 
action of several factors which have already been mentioned in another con- 
nection: The rate and volume of the heart-beat, the elasticity of the blood 
vessels, the resistance of the microscopic peripheral vessels, and the volume 
of blood in the body. We have already learned, page 205, that both the 
rate and volume of the contractions of the heart are under very minute 
and intimate regulation and control through the cardiac nervous mechanism. 
Also we have found that there is intimate co-ordination between the activity 
of the heart and the activity of all other parts of the body, a co-ordination 
secured through the nervous system. All regulation which affects the 
heart must of necessity affect the general blood-pressure and, therefore, 
not directly any particular part. 

The general elasticity of the blood vessels, and of the arteries in par- 
ticular, which makes the general arterial pressure possible, is dependent 
primarily on the presence of a large amount of elastic connective tissue in 
the walls of the vessels. The elasticity of this tissue is a purely passive 
property which can be utilized only by some positive source of energy, in 
this instance the heart. 

The Variations in Peripheral Resistance. Certain arteries and 
veins, especially the smallest ones, the arterioles and venules, are supplied 
with muscular tissue in their walls. The activity of these muscles in the 
vascular complex makes the peripheral regulation of the flow of blood 
possible. This muscular tissue not only exhibits a passive elasticity 
comparable to that of the yellow elastic connective tissue, but upon the 
proper stimulation it actively contracts or relaxes, thus securing to the per- 
ipheral resistance of the vessels an active adjustment to the ever- varying 
dynamic conditions of the vascular apparatus. 

The muscular tissue in the vessels increases relatively in amount as 
the vessels become smaller. In the arterioles it is developed out of all 
proportion to the other elements. In fact, in passing from the arterioles 
to the capillary vessels, made up as we have seen of endothelial cells with a 
supporting ground substance only, the last change on the side of the arteries, 
which occurs as the vessels become smaller, is the disappearance of 
muscular fibers. 

The office of the muscular coat is to adjust the size of the arterioles and, 
therefore, the flow of the blood. It is to regulate the quantity of blood to be 
received by each part or organ, and to adjust this quantity to the requirements 
of each, according to various circumstances, but chiefly according to the de- 


gree of activity which each organ at different times exhibits. The amount of 
work done by each organ of the body constantly varies, and the variations 
often quickly succeed each other, so that, as in the muscles for example, 
within the same hour a part may be now very active and now quite inactive. 
In all its active exercise of function, such an organ requires a larger supply of 
blood than is sufficient for it during the times when it is comparatively 

It is evident that the heart cannot regulate the blood-supply to each 
part of the body at different periods independently of the other parts. 
Neither could this be regulated by any general and uniform contraction of 
the arteries. But it may be regulated by the power which the arteries of 
each part have, through their muscular tissue, of contracting or relaxing 
so as to diminish or increase their size. Since the general blood pressure 
is fairly constant the size of the local vessels controls the supply of blood to 
the particular part of the body to which the vessels are distributed. Thus, 
while the ventricles of the heart determine the total quantity of blood to be 
sent onward to each contraction and the force of its propulsion, and while 
the large and merely elastic arteries distribute the blood and equalize its 
stream, the smaller arteries regulate and determine the .proportion of the 
whole quantity of blood which shall be distributed to each particular 

The variation of the size of arterioles and, therefore, of the resistance 
to the flow of the blood in them is secured by the contractions of the mus- 
cular tissue, but the muscles are regulated in their contractions by the 
nervous system. The muscular tissue in the blood vessels of the organs 
of the different parts of the body is also co-ordinated by the same regu- 
lative and controlling influence of the nervous system. 

The Discovery of the Vaso-motor Nerves. More than half a cen- 
tury ago (1851) it was shown by Claude Bernard that if the cervical sym- 
pathetic nerve is divided, the blood vessels of the corresponding side of the 
head and neck become dilated. This effect is best observed in the ear, 
which if held up to the light is seen to become redder and the arteries to 
become larger. The whole ear is distinctly warmer than the opposite one. 
This effect is produced by removing the arteries from the tonic influence of 
the central nervous system, which influence normally passes along the course 
of the divided nerve. 

If the peripheral end of the divided nerve be stimulated in its course 
toward the organ, i.e., that farthest from the brain, the arteries which were 
before dilated return to their natural size, and the parts regain their former 
condition. And, besides, if the stimulus is very strong or very long-continued, 
the amount of normal constriction is passed and the vessels become much 
more contracted than before. The natural condition, which is midway 
between extreme contraction and extreme dilatation, is called the natural 



tone of an artery. If this is not maintained, the vessel is said to have lost 
tone, or, if it is exaggerated, the tone is said to be too great. The effects 
described as having been produced by section of the cervical sympathetic 
and by subsequent stimulation are not peculiar to that nerve and the vessels 
to which it is distributed. 

A B 

FIG. 201. Small Artery and Vein of the Frog's Web. A, Under normal conditions; 
B, upon stimulation of the sciatic nerve; Ar, artery; V, vein. In this experiment the vein 
also showed well-marked vaso-constriction. (Greene.) 

It has been found that for every part of the body there exists a nerve the 
division of which produces the same effects, viz., dilatation of the vessels. 
Such may be cited as the case with the sciatic, the splanchnic nerves, and 
the nerves of the brachial plexus; when these are divided, dilatation of the 
blood vessels in the parts supplied by them takes place. It appears, 
therefore, that nerves exist which have a distinct control over the vascular 
supply of every part of the body. These are called vase-motor or vaso- 
constrictor nerves. But the arterioles are also under the influence of a 
second set of nerves, also discovered by Claude Bernard, which produce 
exactly the opposite influence, i.e., dilatation. These nerves are called vaso- 
dilator nerves. 

Mall has also shown that veins, at least the postal vein, possess a vaso- 
motor nerve supply as well as arteries. 

Vaso-constrictor Nerves. The presence of vaso-constrictor nerves 
can be shown in several different ways, of which the most convincing is that 
of direct inspection. If a vascular membrane, like the web of the frog's 



foot or the bat's wing, be adjusted on the stage of a microscope for direct 
inspection, and the smaller arterioles are under observation, then upon the 
stimulation of the general nerve supplying the part these arterioles will 
sharply decrease in size. In fact, the vaso-constriction is often so great as com- 
pletely to occlude the vessel. Very soon after the stimulation the vessel 
again dilates to its normal size. 

The presence and course of the vaso-constrictor nerve supply to the 
organs of the body have been demonstrated not by direct inspection, but 
by the use of various forms of the plethysmograph. A plethysmograph is an 

FIG. 202. Arm Plethysmograph. Apparatus for measuring the change in volume in 
the arm due to variation in the blood supply. The arm is enclosed in a glass cylinder 
which is completely filled with fluid, the opening through which the arm is inserted being 
closed by a rubber sleeve, A. The cavity of the glass cylinder communicates through the 
tube, F, G, with the test-tube, M, which is supported in the jar, P. Any variation in 
volume in the arm will cause water to flow out or into the test-tube, M, which is lowered 
as the tube fills, and raised as it empties. The rise and fall of the test tube, M, is com- 
municated over the pulley, L, to the writing pen, N, which records the movements on the 
smoked cylinder. Kymograph not shown. (Mosso.) 

instrument designed to measure the variations in the volume of an organ. 
If the finger, the whole hand, the spleen, or the kidney be placed in such an 
instrument and the proper steps be taken to record the volume changes, it 
will be found that the volume of the enclosed organ is constantly changing 
with every variation of the blood-pressure. If the nerves to the organ are 


stimulated by the usual rapidly interrupted induction current, for example 
the splanchnics to the kidney, then there is a decrease in the volume of the 
organ. This decrease takes place even when there is a simultaneous in- 
crease of the arterial blood-pressure, a result that can be explained only on 
the assumption of vascular decrease in the organ. The decrease in the flow 
of blood to the specific organ can be induced only by a great decrease in the 
size of the arterioles produced by contractions of the circular muscles of 
their walls. 

a b 

FIG. 203. Plethysmograms of the Hind Leg of the Cat, showing a, vaso-contriction 
on stimulating the sciatic at the rate of 15 stimuli per second for twenty seconds. In b, 
the dilation of the blood vessels of the opposite leg of the same animal is shown on 
stimulating the sciatic which had been cut four days previously. The vaso-con- 
strictor nerves were degenerated and the vaso-dilators still active. (Bowditch and 

Vaso-motor Tone. Vaso-constrictor changes are constantly occur- 
ring in the blood vessels of the organs of the body, a fact that has been 
abundantly demonstrated by the plethysmographic experiments just men- 
tioned. Direct inspection of the ear of an albino rabbit will show that the 
arteries, and veins as well, are now full and large and red, and the inter- 
spaces filled with blood, and now pale and constricted, and the interspaces 
relatively bloodless. If the cervical sympathetic is cut as in Bernard's 
experiment, then the ear vessels remain dilated, that is they lose their 
tone. This shows that the condition is dependent primarily on the con- 
stant discharges of nerve impulses from the nervous system. It is said 
that the vessels regain their tone after a time when the nerves are cut. 
The regained power may be ascribed to the muscle fibers themselves. 

Vaso-constrictor Center. When the tonic influence exerted by the 
nerve fibers on the arterioles is traced back into the central nervous system, 
it is found to be associated with the activity of certain groups of nerve cells, 
or centers, which are called the vaso-constrictor centers. This determi- 
nation is made in part by the method of sectioning. A lesion of the 
cerebro-spinal axis below the corpora quadrigemina is followed by partial 
or complete general dilatation of the blood vessels and a great fall of blood- 
pressure. This is due to the isolation of the vaso-constrictor center, which 
lies in the floor of the fourth ventricle, a few millimeters caudal to the 
corpora quadrigemina, and extends longitudinally over an area of about 
three millimeters. Owsjannikow has shown that the center is composed of 





two halves, each half lying in the lateral column to the side of the median 
line. This center is in constant action during life, and its discharges are 
responsible for the vascular tone described in the previous paragraph. 
The vaso-constrictor center varies in its activity, sometimes producing 
wave-like contractions with relaxations of the arterial walls, producing 
variations in the blood-pressure known as Traube- 
Hering waves. These waves are more of ten observed 
in mammalian blood-pressure experiments after pro- 
longed operations, when the center may be supposed 
to be itself in a weakened condition. 

Secondary vaso-motor centers are present in the 
spinal cord as proven by Goltz. Under normal con- 
ditions they do not act independently of the medul- 
lary center; but when the function of the latter has 
been interrupted by section of the cord, then after 
a few days the spinal cells below the section take 
on central functions and bring about a re-establish- 
ment of the lost vascular tone. If these centers be 
destroyed by the destruction of the cord, then the 
tone of the vessels immediately disappears, but is 
regained after the lapse of a much longer time. This 
can be ascribed to the presence of possible sympa- 
thetic constrictor centers or more probably to a 
fundamental property of the muscles themselves. 
This experiment was carried out by Goltz and 
Oswald, who found that after destruction of the 
lower part of the spinal cord, the tone of the vessels along the Cervical Sym- 
of the hind limbs, lost as a result of the operation, 5 SpUnchnic. 
was later re-established. Aur. Artery of ear; G. 

Vaso-constrictor Reflexes. Under normal con- gangiion^^w. F, au- 
ditions the medullary center responds to afferent nulus of Vieussens; G. 
stimuli by vaso-motor reflexes. The secondary vaso- j ' ^jf pV thoracic 
motor centers in the spinal cord, when removed from spinal nerves; Abd. Spl, 
the influence of the bulbar center, can and do ^he^rows indicate the 
respond to afferent impulses by similar vaso-motor direction of vaso-con- 
strictor impulse, 

The afferent impulses which excite reflex vaso-motor action may pro- 
ceed from the terminations of sensory nerves in general, or possibly from 
the blood vessels themselves, and the constriction which follows generally 
occurs in the area whence the impulses arise. Yet the reflex may appear 
elsewhere. Impulses proceeding to the vaso-motor center from the cere- 
brum may cause vaso-dilatation, as in blushing, or vaso-constriction, as in 
the pallor of fear or of anger. 

FIG. 204. Diagram 



Afferent influence upon the vaso-motor centers is well shown by the 
action of the depressor nerve, the existence of which was demonstrated by 
Cyon and Ludwig. The depressor is a small afferent nerve which passes 
up to the medulla from the heart, in which it takes its origin. It runs up- 
ward in the sheath of the vagus or in the superior laryngeal branch of the 
vagus or as an independent branch, as in the rabbit, communicating by 
filaments with the inferior cervical ganglion as it proceeds from the heart. 
If, in a rabbit, this nerve be divided and the central end stimulated during 
a blood-pressure observation, a remarkable fall of blood-pressure takes 
place, figure 205. 

FIG. 205. Blood-pressure Record (lower) and Respiratory Record (upper) Obtained 
from a Dog upon Stimulating the Central End of the Divided Vagus, Both Vagi being Cut. 
The marked fall in blood -pressure is due to the effect of stimulating the depressor fibers 
contained in the vagus trunk of the dog. (New figure by Dooley and Dandy.) 

The cause of the fall of blood pressure is found to proceed primarily 
from the dilatation of the vascular district within the abdomen supplied by 
the splanchnic nerves, in consequence of which the vessels hold a much 
larger quantity of blood than usual. The engorgement of the splanchnic 
area very greatly diminishes the amount of blood in the vessels elsewhere, 
and so materially diminishes the blood-pressure. The function of the de- 
pressor nerve is that of conveying to the vaso-motor center afferent nerve 
impulses from the heart, which produce an inhibition of the tonic activity 
of the vaso-motor center and, therefore, a diminution of the tension in the 
blood vessels. This diminishes the overstrain on the heart in propelling 
blood into the already too full or too tense arteries. It has been shown by 
Porter and Beyer that the fall in blood-pressure, following stimulation of the 
depressor nerve, will still occur, even when the abdominal vaso- constriction 
is kept constant by a simultaneous stimulation of the splanchnics. It is 
therefore evident that the inhibitory effect of depressor- nerve stimulation is 
a general one and not confined to the splanchnic area alone. 


The action of the depressor nerve in causing an inhibition of the vaso- 
motor center illustrates the more unusual effect of afferent impulses; that is, 
inhibition of the vaso-constrictor tone. As a rule, the stimulation of the 
central end of an afferent nerve, such as the sciatic or the internal saphenous, 
produces the reverse, i.e., a pressor effect, and increases the tonic influence 
of the center which by causing constriction of the arterioles raises the blood 
pressure. Thus the reflex effects of stimulating an afferent nerve may be 
either to constrict or to dilate the arteries. These reflexes may be general 
enough to influence the general blood-pressure or they may be limited to 
definite local areas, but the local effects are the all-important ones, since 
by these the local regulation of the blood flow is accomplished. 

Traube-Hering Curves. The vaso-motor center sends out rhythmical 
impulses by which undulations of blood-pressure of a large and sweeping 
character are produced, quite independent of the so-called respiratory un- 
dulations. The action of this center in producing such undulations is dem- 
onstrated in the following observations. In an animal under the influence 
of curare and with both vagi cut, and a record of whose blood-pressure is 
being taken, if artificial respiration be stopped, the blood-pressure rises 
sharply at first. After a time the rhythmical undulations shown in figure 206 
occur. These variations are called Traube's or Traube-Hering curves. 
There may be upward of ten of the respiratory undulations in one Traube- 
Hering curve. They continue until the vaso-motor center is asphyxiated 
and the heart exhausted, when the pressure falls. The undulations cannot 
be caused by anything but the vaso-motor center, as the mechanical effects 
of respiration have been eliminated by the curare and by the cessation of 
artificial respiration, and the effect of the cardio-inhibitory center has been 
removed by the division of the vagi. The rhythmic rise of blood-pressure 
is most likely due to a rhythmic constriction of the arterioles followed by a 
corresponding relaxation and fall of pressure, both being due to the action 
of the vaso-motor center. The vaso-motor center, therefore, is capable of 
producing rhythmical discharges of vaso-constrictor nerve impulses that 
result in the undulations of blood-pressure. 

Vaso-dilator Nerves. Claude Bernard discovered (1856) that the 
blood flow was increased through the salivary glands by stimulation of the 
nerves (the chorda tympani for the submaxillary, and the tympanic branch 
of the glossopharyngeal for the parotid), thus proving that the arteries have 
not only vaso-constrictors, but also vaso-dilator nerves. Vaso-dilator nerves 
have been described for most parts of the body. In general they are dis- 
tributed in the same nerve trunks which bear the vaso-constrictors. 

It is not supposed that the vaso-dilators produce widening of the 
arterioles by stimulation to active muscular contraction; in fact, the circular 
arrangement of the muscle fibers would seem to exclude such a deduction. 
It is probable that there is local inhibition of the tonic contraction of the 


muscles, thus allowing the mechanical factor of the general blood-pressure 
to dilate the vessels. The vaso-dilator nerves are characterized by their re- 
sponse to slowly developed stimuli, shown by Bowditch and Warren, 
and by the retention of irritability after degeneration of the constrictors 
has taken place, see figure 203. 

FIG. 206. Traube-Hering's Curves. (To be read .from left to right.) The curves 
i, 2, 3, 4, and 5 are portions selected from one continuous tracing forming the record of a 
prolonged observation, so that the several curves represent successive stages of the same 
experiment. Each curve is placed in its proper position relative to the base line, which is 
omitted; the blood-pressure rises in stages from i to 2, 3, and 4, but falls again in stage 5. 
Curve i is taken from a period when artificial respiration was being kept up, but, the vagi 
having been divided, the pulsations on the ascent and descent of the undulations do not 
differ; when artificial respiration ceased, these undulations for a while disappeared, and the 
blood-pressure rose steadily while the heart-beats became slower. Soon, as at 2, new 
undulations appeared; a little later, the blood-pressure was still rising, the heart- beats still 
slower, but the undulations still more obvious 3; still later 4, the pressure was still 
higher, but the heart-beats were quicker, and the undulations flatter; the pressure then 
began to fall rapidly 5, and continued to fall until some time after artificial respiration was 
resumed. (M. Foster.) 

Vaso-dilator Centers. No distinct medullary center has yet been shown 
to regulate the vaso-dilator nerve activity. Such centers, if they exist, 
should be influenced by isolating them from their efferent paths, on the one 
hand, or by stimulation by afferent channels, on the other. The former 
method of study has revealed nothing that can be compared to the tonic ac- 



tivity of the constrictor center. Efferent dilator-nerve impulses can be re- 
flexly produced by sensory stimulation. The isolated lumbar cord of a dog 
is capable of reflex vaso-dilator activity, since stimulation of the skin of 
the penis leads to reflex vaso-dilatation, indicating the presence of local 
vaso-dilator reflex mechanisms or paths through the lumbo-sacral portion 
of the spinal cord. 


Weak Ind. 10-19 

Medium Ind. = 100-250 

Strong Ind. = 300-800 


rate per 

No. of 




No. of 



No. of 







I . 2 



i .9 

































n. 4 





2. I 





14.6 1.4 


Vaso-dilator Reflexes. Perhaps the only unquestioned case of reflex 
vaso-dilatation is that of the lumbar cord just mentioned. It is true that 
many apparent reflexes can be noted, for example the increased flow of 
blood in the salivary glands under gustatory reflexes, the blushing of the 
skin on exposure to sudden warmth, or even the blushing of emotional 
origin. These on first thought would be regarded as vaso-dilator reflexes. 
In all these cases there is a widening of the peripheral arterioles with a 
great increase in the volume of blood flowing through the local vascular 
bed. But each instance can be just as readily explained as inhibition 
of the vaso-constrictor tonic activity. This double explanation can, as a 
matter of fact, be applied to the action of the depressor nerve described 
above, page 248. However, the confusion is in part due to the diffi- 
culty of analyzing the two classes of nerves in the same nerve trunk. 
All the thoracic spinal nerves and the upper lumbar trunks contain both 
vaso-constrictor and vaso-dilator nerves. The usual methods of physio- 
logical stimulation with rapidly interrupted currents we now know are 
normal stimuli for the constrictors only. Stimulations at the rate of one 
or two per second call forth responses in the dilator fibers. Also, the vaso- 
dilator fibers degenerate more slowly and retain their irritability longer 
than the constrictor fibers when both are isolated from their cell bodies 
by sectioning. The method of slow stimulation and the method of differ- 
ential degeneration were given us by Bowditch and Warren. 


The Relation of Vaso-constrictor and Vaso-dilator Activity. The 
distribution of two sets of regulative fibers for the muscular walls of the 
blood vessels, when considered in connection with the other factors of the 
vascular apparatus, gives a wonderfully complete mechanism for the co- 
ordination of the vascular supply with the activity of the different organs. 
General and broadly distributed activity of the constrictors produces 
increase of general blood pressure and of the dilators decrease of pressure, 
but local activity of either set will produce a great reduction or increase of 
blood in the local organ with little or no effect on the general pressure. 
When a vaso-dilatation is produced locally in one organ and there is an 
accompanying vaso-constriction in other regions, as usually happens, it is 
evident that the result may be a flooding of the local region. This is 
exactly the thing that is accomplished in the muscles in violent exercise, 
in the glands during secretion, in the stomach during digestion. It is 
this mechanism that is utilized to throw a large volume of blood to the 
skin when the temperature of the body is above the average, or to blanch 
the skin when the temperature is low. 

Normally certain regions of the body are associated in that when vaso- 
dilatation occurs n one region, vaso-constriction occurs in the other. This is 
particularly true with the skin or surface of the body and the viscera or deeper 
organs. The same relation is said to exist between some of the visceral 

General Course of the Vaso-constrictor and Vaso-dilator Nerves. 
The cell bodies forming the medullary vaso-motor center give off axones, 
axis- cylinder processes, some of which go to the nuclei of origin of certain 
cranial nerves, while others pass down the cord to end at different levels 
in contact with certain cells, probably small cells in the anterior horn and 
lateral part of the gray matter. These cord cells constitute the spinal centers. 
The neuraxones of the spinal cells leave the cord in certain spinal nerves in 
the anterior roots, pass by the white rami to the sympathetic ganglionic 
chain, where they end in physiological connection with the ganglionic cell. 
Axones from these latter cells pass by an uninterrupted course to their termina- 
tions on the blood vessel walls. The vaso-constrictor fibers leave the central 
nervous axis by the ventral roots of all the dorsal nerves and the first two 
lumbar roots, a comparatively restricted region. The vaso-dilators have 
the same origin with two exceptions, viz., the vaso-dilators of the salivary 
glands found in the seventh and ninth cranial nerves, and the nervi erigentes, 
which arise in the roots of the second and third sacrals. 

The nerves to the viscera pass direct to their blood vessels, but the vas- 
cular nerves for the skin, muscles, limbs, etc., rejoin the main divisions of the 
spinal nerves through the gray rami, see figures 417 and 418, and pass to the 
blood vessels along with the general nerves of the organ or organs. 



The particular paths for the vaso-motor nerves has been pretty definitely 
established by numerous researches, especially by those of Langley and his 

The course of the vaso-constrictor and the vaso-dilator nerve fibers has 
been followed satisfactorily in many of the important parts of the body, 
though the supply for some regions is yet obscure. This is particularly 
true for the brain, where such supply is apparently absent. The two groups 
of fibers run the same course, except in the cephalic and sacral regions already 
mentioned They may, therefore, be described together. 

The Vascular Nerve Supply for the Head. The vascular nerves 
for the head, face, and mouth have their origin in the cord from the first to 
the fifth dorsal spinal nerves. They pass through the white rami to sym- 
pathetic ganglia, through the stellate ganglion, and up the cervical sympa- 
thetic nerve to the superior cervical ganglion. From this ganglion they run 
to their distribution, either along with the arteries, as with the salivary sup- 
ply, or with the sensory nerves, as in the nerves to the mucous membrane 
of the mouth, etc. The vascular nerves supplied to the base of the ear follow 
the above course, but the nerves for the tip leave the stellate ganglion in the 
ramus vertebralis, run to the third cervical nerve, and pass with its auricular 
branch to the ear, a circuitous route determined by Fletcher. 

The great exception to the above origin is with the vaso-dilator group. 
Dilator fibers leave the base of the brain in the direct path of the seventh 
cranial nerve to supply the submaxillary and sublingual glands, in the ninth 
cranial nerve to the parotid gland, and in both these to the tongue. 

The Vascular Regulation in the Brain. The brain requires a large 
and uniform supply of blood for the due performance of its functions. This 
object is effected through the number and size of its arteries, the two internal 
carotids and the two vertebrals. It is also desirable that the force with 
which this blood is sent to the brain should be subject to less variation from 
external circumstances than it is in other parts, an effect that is accomplished 
by the free anastomoses of the large arteries in the circle of Willis. This 
arrangement insures that the supply of blood will be uniform in both hemi- 
spheres even though it may^be limited through operation or accident to one 
or more of the four principal arteries. Uniformity of supply is further 
insured by the arrangement of the vessels in the pia mater. Previous to 
their distribution to the substance of the brain the large arteries break up 
and divide into innumerable minute branches. These arterioles after 
frequent communication with one another enter the brain in a very uniform 
and equable distribution. The arrangement of the veins within the cranium 
is also peculiar. The large venous trunks or sinuses are formed so as to be 
scarcely capable of change of size; and composed, as they are, of the tough 
tissue of the dura mater, and in someinstancesbounded by the bony cranium, 


they are not compressible by any force which the fullness of the arteries 
might exercise through the substance of the brain. Nor do they admit of 
distention when the flow of venous blood from the brain is obstructed. 

The mechanical conditions in the brain and skull formerly appeared 
enough to justify the opinion that the quantity of blood in the brain must 

FIG. 208. Showing the Origin and Course of the Vaso -constrictor Nerves for the 
Head. M, medulla; C 8 , eighth cervical spinal nerve; V, vagus, S.c.g., superior cervical 
ganglion. Modified from Moret. 

be at all times the same. But it was found that in animals bled to death 
without any aperture being made in the cranium, the brain became pale and 
anemic like other parts. And in death from strangling or drowning, there 
was congestion of the cerebral vessels; while in death by prussic acid, the 
quantity of blood in the cavity of the cranium was determined by the position 
in which the animal was placed after death, the cerebral vessels being con- 
gested when the animal was suspended with its head downward, and com- 
paratively empty when the animal was kept suspended by the ears. Thus, 
although the total volume of the contents of the cranium is probably nearly 
always the same, yet the quantity of blood in it is liable to variation, its in- 
crease or diminution being accompained by a simultaneous diminution or 
increase in the quantity of the cerebro-spinal fluid. The cerebro-spinal 
fluid being readily removed from one part of the brain and spinal cord to 


another, and capable of being rapidly absorbed and as readily effused, would 
serve as a kind of supplemental fluid to the other contents of the cranium 
to keep it uniformly filled. Although the arrangement of the blood vessels 
insures to the brain an amount of blood which is tolerably uniform, yet with 
every beat of the heart, and every act of respiration, and under many other 
circumstances, the quantity of blood in the cavity of the cranium is con- 
stantly varying. Roy and Sherrington are responsible for the view now 
generally current that the brain, therefore, is largely if not entirely dependent 
upon the general blood-pressure for variations in the quantity of blood which 
it receives. During a high blood-pressure the amount of blood that flows 
in a given unit of time is greater, and during low blood-pressure less. Howell 
has shown that in the decapitated dog's brain the flow of blood is directly 
proportional to the difference in pressure. 

Numerous attempts have been made to show vaso-motor mechanisms 
for the cerebral arteries, but with generally unconvincing success. Huber 
and others have shown nerve endings in such arteries by histological 
methods. Bayless, Hill, and Gulland make the statement that "no- 
evidence has been found of the existence of cerebral vaso-motor nerves, 
either by means of stimulation of the vaso-motor center or central end of 
the spinal cord, after division of the cord in the upper dorsal region, or 

FIG. 209. Vaso-dilatation in the Brain from Stimulation of the Cerebral Cortex 
in the Presence of Complete Destruction of the Medulla in the Cat. The upper trace 
is of the carotid pressure; the lower trace is of the brain oncometer. (Weber.) 

by stimulation of the stellate ganglion, and that is to say the whole 
sympathetic supply to the carotid and vertebral arteries." However, 
Ernest Weber (1908) reinvestigated the control of the blood flow in the 
brain. He admits that the blood flow in the brain is sharply dependent 
on the general blood-pressure, but he presents plausible evidence that 
both vaso-constrictors and vaso-dilators exist for the brain vessels. The 
most striking facts are obtained upon stimulating general sensory nerves, 
the central end of the sectioned cord, the cerebral cortex, and the cervical 
sympathetic. The stimulation of the cerebral cortex calls forth vaso- 
dilatation in the brain even when the medulla is completely destroyed. 
Weber, therefore, concludes that these stimuli act reflexly through a 
cerebral vascular center located at some as yet undetermined point in 
the brain stem above the general medullary center. An active cerebral 
vaso-dilatation may be accomplished through this center even in the 


presence of an accompanying fall in general blood-pressure. More often 
the type of vascular reflex is that of dilatation followed by constriction 
of the brain vessels. If there is an accompanying sharp rise in general 
blood-pressure, then the reflex cerebral vascular dilatation is followed by 

nee. ur VES. 

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irl'&iig'^ i 

vaso-constriction which takes place while the general blood-pressure is yet 
high. Weber suggests that this local vaso-constrictor mechanism provides 
an apparatus for the regulation and control of the cerebral congestion 
that results from the rise of general blood-pressure due to the operation of 
the general medullary vaso-motor center. 


The question may be summarized by the statement that the regulation 
of the flow of blood through the brain is accomplished by the interaction of 
two factors: First, the indirect regulation of blood-pressure through the 
variations in the heart's activity, and through the general action of the 
medullary vaso- motor apparatus producing vaso-constrictions or dilatations 
in areas other than the brain. Second, the local and direct regulation of 
the brain vessels through reflex action on a special local vascular center. 

The Vascular Nerves for the Thoracic Viscera. Numerous efforts 
have been made to determine the vaso- motor nerve supply for the thoracic 
organs, the heart and lungs. In the heart the observation is rendered com- 
plex by the fact of the rhythmic contractions which produce mechanical 
pressure on the coronary arteries. Martin, by direct observation through a 
lens, and Porter, by measuring the outflow of the coronaries upon vagus 
stimulation, came to exactly opposite views: the former that the vagus con- 
tained vaso-dilators, the latter that it contained vaso-constrictors. Still 
other experiments have been made to prove either constrictor or dilator 
nerves for the coronary arteries, but the fact is still undetermined. 

The lesser circulation through the lungs has also proven a difficult situa- 
tion to interpret as regards any nervous regulation of the pulmonary arteri- 
oles. The evidence, while not conclusive, is that the vaso-constrictor supply 
to the lungs is from the third to the fifth thoracic nerves, but that the vaso- 
constriction produced is slight in comparison with regions of the systemic 

The Vascular Nerves for the Abdominal Viscera. The vaso-con- 
strictors and the vaso-dilators for the organs of the abdominal cavity have 
a broad origin in the cord, from the first dorsal to the fourth lumbar in 
the dog and cat. The nerves pass to the organs by the splanchnic nerves, 
and by the solar, celiac, and mesenteric ganglia. The vascular nerves for 
the different organs may be given in tabulated form: 

Vascular Nerves for the Abdominal Viscera. 

Organ. Spinal origin of the vascu- Course to the organ. 

lar nerves. 

Stomach and in- \ 5, 6, 7, 8, 9, 10, n, 12, 13 D, / Splanchnic nerves and 

testine. ( i L | solar and celiac ganglia. 

o i ee I 3, 4, 5, 6, 7, 8, 9, 10, n, 12, J Splanchnic nerves and 

/ 13 D, i L | solar and celiac ganglia. 

T -r^ f Splanchnic nerves and 

Liver 3, 4, St 6. 7. 8, 9, 10, nD. . < 

solar and celiac ganglia. 

Kidnev 4> 5> 6 ' 7 ' 8 ' 9> I0 ' "' I2 ' I3 Splanchnic and celiac 

/ D, i, 2, 3, 4 L. \ ganglia. 

Inferior splanchnic and 

Pelvic viscera i, 2, 3, 4!, -J inferior mesenteric 



The Vascular Nerves for the External Genital Organs. The vaso- 
dilators for these organs arise from the second and third sacral nerves and 
pass to the organs by the nervi erigentes and the pelvic plexus. They form 
the second great exception to the region of general outflow of vascular nerves. 
The constrictors, on the other hand, arise in the spinal nerves from the last 
dorsal and first four lumbar. They run the same course as given in the table 
for the pelvic viscera. 

The greatest variations in the quantity of blood contained at different 
times in the external genital organs are found in certain structures which 
contain what is known as erectile tissue. These organs, under ordinary cir- 
cumstances, are soft and flaccid, but at certain times they receive an un- 
usually large quantity of blood, become distended and swollen by it, and 
pass into the state termed erection. Such structures are the corpora cavernosa 
and corpus spongiosum of the penis of the male, and the clitoris in the female. 
The nipple of the mammary gland in both sexes, and, according to some 
authors, certain nasal membranes contain erectile tissue. 

The corpus cavernosum of the penis, which is the best example of an 
erectile structure, has an external fibrous membrane or sheath. From the 
inner surface of the sheath numerous fine lamellae project into the cavity, 
dividing it into small compartments, like cells when they are inflated. Within 
these cells there is a plexus of veins upon which the erectile property of the 
organ mainly depends. The plexus consists of short veins with very close 
interlacings and anastomoses with very elastic walls admitting of great varia- 
tions in size. They collapse in the passive state of the organ, but are capable 
of an amount of dilatation which exceeds beyond comparison that of the 
arteries and veins which convey the blood to and from them. The strong 
fibrous tissue lying in the intervals of the venous plexuses, and the external 
fibrous membrane or sheath with which it is connected, limit the distention 
of the vessels and give to the organ its condition of tension and firmness. 
The same general condition of vessels exists in the corpus spongiosum 
urethrae, but the fibrous tissue around the urethra is much weaker than 
around the body of the penis, while around the glans there is none. The 
venous blood is returned from the plexuses by comparatively small veins; 
all of which are liable to the pressure of muscles where they leave the penis. 
The muscles chiefly concerned in this action are the erector penis and 
accelerator urinae. Erection results from the distention of the venous 
plexuses by a sudden influx of blood resulting from the action of the nervous 
vascular reflexes. It is facilitated by the special muscular mechanism 
which prevents the outflow of blood. 

The Vascular Nerves for the Trunk and Limbs. The skin and 
muscles of the trunk receive their cutaneous and motor nerves by a seg- 
mental arrangement in which the innervation is by bands corresponding 
with the segments of the cord and the spinal nerves. It is much the same 



with the vascular nerves; they are distributed to the skin and walls of the 
trunk in the same segment in which they arise. Langley says that the suc- 
cessive bands overlap somewhat. 

In the fore legs or arms the vascular nerves arise from the first to the 
sixth dorsal spinal nerves, run to the stellate ganglia, then by the gray rami 
back through the ramus vertebralis to join those cervical nerves that enter 
into the brachial plexus, figure 211. 

FIG. 211. Plan of Distribution of Vaso-constrictor Nerves for the Fore Limbs. 
(Modified from Moret.) 

The nerves for the blood vessels of the lower limbs arise from the tenth 
dorsal to the second lumbar nerves. These pass to the ganglionic chain, and 
gray rami are given off which join the lumbo-sacral plexus and run with the 
divisions of that nerve complex to their distribution in the skin and muscles. 
Vaso-constrictors and vaso-dilators have a common course to the lower limbs. 

The Vaso-constrictor Nerves for the Veins. Mall has proven that 
vaso- constrictors are present for the portal vein. These fibers are present 
in the splanchnic nerves. Other evidences have been observed which 
render the view probable that vaso-motors for the veins in general exist. 
Hough, for example, in an extended study of the capillary pressure found 
many variations which were readily explained only on the assumption of 
veno- motor activity, see figure 201. 



1. The Rate of the Human Heart-beat. Determine the rate of the 
heart-beat per minute by counting the radial pulse, using a watch for the 
time. Make the determination after sitting quietly for five minutes. 
Take the average of at least ten determinations for your own case. Deter- 
mine the heart-rate under the same conditions for as many different per- 
sons as you can. Tabulate these rates to show age, sex, weight, and 
height of the different classes of individuals, and compute general averages 
for your sets. Count the rate in children and in aged. 

Note the effect on the averages obtained above after lying down for 
five minutes, after standing quietly for the same time, and after five 
minutes' brisk walk. Tabulate as directed. 

Count the heart-rate by successive 15 second periods immediately 
upon standing from the reclining position and until the quarter minute 
rates are constant; repeat immediately after two minutes of fast running. 
Tabulate these results and compare the graphs obtained from several 
different individuals. This method measures the character of the vascular 
control in certain clinical states. 

Count your own heart-rate at one-hour intervals during one entire 
day, giving special attention to the rate just before and just after meals, 
but in every case make the count on the fifth minute while sitting quietly. 
A marked diurnal variation will usually appear. Determine these rates 
on several individuals, and tabulate as before. 

2. Human Cardiogram. Apply a Burdon-Sanderson cardiograph 
to the thorax over the point between the fifth and sixth ribs of the left 
side, where the cardiac impulse is felt most distinctly. Connect the 
cardiograph with a recording tambour, Marey's form, adjust the tension 
of the cardiograph and the pressure of the air within the system, and take 
a tracing of the movements of the lever of the recording tambour. The 
recording cylinder should travel at the rate of about two centimeters per 
second. Take the time of the movements of the kymograph by an elec- 
tric seconds magnet. The proper description should be written on the 
smoked paper, the paper removed carefully and the whole record fixed in 

Count the rate of the heart-beat from the record. Compute the time 
of the cardiac systole and diastole, and of the pause at the end of the diastole 
in seconds to three decimals. Records secured under different condi- 
tions of exercise, etc., brought together in a table will usually show that the 
higher heart-rates decrease the time of the cardiac cycle at the expense of 
the diastole. In other words, the time of the systole remains fairly 
constant, while the time of the diastole increases or decreases inversely 
with the rate, a fact to which Hiirthle has drawn attention, figure 157. 



3. The Rate and Sequence of the Contractions of the Frog's Heart. 
Destroy the brain of the frog and open the thorax, but do not destroy 
the pericardium. Count the rate of the heart per minute, then remove the 
pericardium and make a second determination after the heart is exposed 
to the air. The different parts of the heart are easily identified and 
the contractions in definite sequence can be determined without difficulty. 
Make this determination for the ventricle, auricle, and sinus venosus by 
direct observation. 

Prepare a cardiac lever as shown in figure 212 or 216, taking special 
care to arrange the foot so that it will not bind when in motion. Adjust 
the foot of the lever on the exposed ventricle and bring its point to write 

FIG. 212. Heart Lever for Frog or Turtle Hearts. This lever rests directly on 
the surface of the heart, the foot consisting of a tiny piece of dry cork bark. The 
lever can also be used as in figure 216, in this case by attaching the tip of the apex 
of the ventricle by a tiny hook and thread to the short axis of the lever. Either de- 
vice can be used for taking records of cardiac sequence. 

lightly on the smoked paper of a recording cylinder. This cylinder should 
travel at the rate of about 2 cm. per second and its speed be marked by the 
writing point of an electric magnet. Take care to adjust the time magnet 
in a vertical line with the writing point of the heart lever, placing the 
heart lever about i cm. above. The tracing of the ventricle, the cardio- 
gram, will show rhythmic contraction, relaxation, and pause of the ven- 
tricle. It will also enable one to measure the exact proportion of the total 
time of the cardiac cycle consumed by the systole and diastole, and also 
that portion of the diastole in which the ventricle is wholly at rest. A 
drum rate of 2 mm. per second gives a more satisfactory record of varia- 
tions when amplitude and rate alone are studied. 



After one has obtained ventricular tracings and has learned the diffi- 
culties of adjusting the apparatus, a second heart lever should be adjusted 
to the auricle, and the auricular movements recorded at the same time as 
those of the ventricle. If some care is taken to adjust these two writing 
points in a vertical line a splendid tracing showing synchronism between 

FIG. 213. Cardiogram Showing Contractions of the Auricle, a, and Ventricle, v 
of a Frog. Time in seconds. The record shows the sequence of the auricle and ventricle, 
(New figure by Dooley.) 

auricle and ventricle is obtained. Measure the rate and the time of the 
different phases of the contractions of the auricle and ventricle and 
tabulate them in the following form, always expressing fractions in the 
decimal system: 

Rate per 

Time of systole 
in seconds 

Time of diastole 
in seconds 

Time of pause 
in seconds 



4. Sequence, Conduction and Heart Block, Turtle Heart. Prepare a 
turtle, expose the heart and determine the rate and sequence of the 
parts. Observe that the veins are contractile. 

a. Make simultaneous records of the right auricle and the ventricle, 
use speeds of 2 mm. and 2 cm. per second. 

b. Attach a GaskelPs clamp close against the ventricle in the a-v 
groove. While taking records slowly compress the clamps by steps until 
the ventricular rhythm begins to slow down. Produce partial block 
through 2 auricles to i ventricle, 3 to i, 4 to i, etc., rhythms, until com- 
plete block is obtained. Note recovery on removing the clamp. 

c. While recording the contractions of the right and left auricles by 
separate levers split the heart into right and left halves. The right half 
will continue the usual rhythm, the left will be slower but show more 
tone. These halves will respond to nerve control and to block tests. 



5. The Contractions of the Excised Heart of the Frog Pith a frog 
and expose the heart, as described in the preceding experiment. Re- 
move it completely from the body by first cutting the arteries at their 
branching in front of the bulbus arteriosus, then carefully lifting up the 
parts of the heart and cutting away the great veins where they enter the 
sinus. This will remove the entire heart, including all its contractile 
parts. The frog's heart, when thus removed and still wet with its own 
blood, will continue contracting rhythmically and in its natural sequence 
for some hours. Place such an isolated heart in a watch-glass and take a 
record of its contractions by the apparatus described in the preceding 
experiment. (The same phenomena may be studied on a heart isolated 
and mounted in a Williams' apparatus.) 

Set this watch-glass on the metal warming-box supplied, and arrange 
for the circulation of water of different temperatures through the box. 
Vary the temperature of the box, and therefore of the heart placed upon it, 
by allowing water of o C., 10 C., 20 C., 30 C., 40 C., to flow through 
it. Or place the heart in a watch-glass over a drinking glass of water of the 
proper temperature. Record the contractions of the heart at each of 
these temperatures. The exposed heart will not take the same absolute 
temperature as the box, but the relative temperature will be decreased or 
increased. Tabulate the rates at these different temperatures by the 
plan previously described. 

6. The Perfused Heart, Influence of Different Nutrient Fluids. Expose 
a frog's heart, as previously described, and insert a 4-way cannula into 
the ascending vena cava where it 

enters the sinus. Connect the 
limbs of the venous cannula with 
Mariotte's bottles. Fill one with 
Ringer's solution, the other with 
comparison fluids. Adjust the con- 
stant level tube for a pressure of 
4 cm. of fluid and allow it to flow 
through the heart. The heart will 
continue its contraction's in good 
sequence and with a uniform rate. 
Record the contractions by the 
Engelmann lever method on 
smoked paper, together with a 
time tracing in seconds. Set the 
drum at the rate of about 2 mm. 

per second. After each compari- 

- . . . .. FIG. 214. Roy's Tonometer, 

son is made Ringer s fluid should 

be perfused to secure a return of the normal contractions. 


Use the tracing obtained under the influence of Ringer's solution as a 
normal and compare it with the rate and amplitude of the contractions 
when the heart is perfused with: 

a. Physiological saline solution, then return to Ringer's solution; 

b. With saline and potassium chloride in the proportions found in 
Ringer's solution (.7 per cent sodium chloride + .03 per cent potassium 
chloride) ; 

c. With saline and calcium chloride in the proportions found in Ringer's 
solution (.7 per cent sodium chloride + .026 per cent calcium chloride);, 

d. With Locke's solution; 

e. With milk diluted 4 volumes with physiological saline; 
/. With normal serum, or blood; 

g. With blood, or serum, diluted four times with saline. 
Tabulate the rates and amplitudes of the heart under these different 
influences by the method previously followed. 

7. The Heart Volume. Isolate a frog's heart by the method de- 
scribed for perfusing it with fluid in the preceding experiment. Connect 
it in a Roy's tonometer, see figure 214, adjust the lever of the tonometer 
for a tracing on smoked paper. This instrument records the change in 
volume with each heart contraction. The influence of pressure, varied 
between 2 and 10 cm., and of nutrient fluids on the heart volume may be 

An instructive demonstration can be had by placing the heart of the 
cat or dog in a Henderson plethysmograph and recording the volume 
changes by the tambour method. 

8. The Isolated Heart of the Terrapin. The heart of the terrapin, 
being somewhat larger and somewhat more responsive than the heart of the 
frog, may be substituted in the two immediately preceding experiments. 
The facts obtained from it will be essentially the same as those obtained 
from the frog's heart. 

9. The Isolated Mammalian Heart. The mammalian heart may be 
isolated from the body and kept alive and contracting for many hours, 
as has been demonstrated by numerous observers. It is only necessary 
to keep the temperature approximately that of the normal body and to- 
perfuse the heart through the coronary circulation with aerated blood, 
or diluted blood, containing sufficient, aerated hemoglobin to supply the 
heart with the requisite amount of oxygen. Or the heart may be kept 
alive on the inorganic salt solutions, provided these are supplied with 
oxygen under considerable tension (Porter, Howell). Even the human 
heart has been isolated and kept contracting for some hours in the above 
manner (Kuliabko). The method used is to insert a cannula into the 
aorta and perfuse the heart through the coronary circulation under ade- 
quate pressure, as described by Martin. Many interesting experiments 


and demonstrations can be made on the mammalian heart, but, as this, 
experiment is usually a demonstration experiment, the detail of procedure 
is left to be supplied by the demonstrator. 

10. Automatic Contractions of Cardiac Muscle. Isolated portions of 
the dog's ventricle have been kept in rhythmic contraction by Porter. 
But the best laboratory material is supplied by the heart of the terrapin. 
Cut a strip from the ventricle of the terrapin extending around its curved 
apex, as shown by the dotted line in the accompanying figure, 215. Split 
this strip longitudinally into two parts, each of which will then be about 
3 to 4 mm. in diameter by 3 cm. long. Use care to cut smooth strips. 
Tie a silk thread around the extreme tips of each end of the strip, tying a 
loop of about i cm. long at one end, and about 10 cm. long at the other. 
Suspend the strip over a glass hook, figure 216, by the short loop, and con- 
nect it with a heart lever by the long loop, as shown in the same figure. 
Use a tension of i gram. Contractions of this strip as arranged will be 
recorded with a magnification of about five and with the upstroke of the 
lever, which is convenient for reading and interpretation. Keep the strip 
moist with physiological saline in a specimen tube i by 3 inches in size. 
The arrangement of apparatus figured makes it possible easily and 
quickly to change this solution for any other that may be desired. 

PIG. 215. Heart of the Terrapin to Show the Method of Cutting the Apex Strip. V f 
Ventricle; Au, auricles; Vc, venae cavae; Ao, aorta. 

Contractions of the ventricular strip in saline begin in from 10 to 
40 minutes after the preparation is made, and go through a regular sequence 
of slight increase in rate and amplitude for from 10 to 20 minutes, followed 
by a very constant rate, but gradually decreasing amplitude for a period of 
from 2 to 3 hours, figure 171. Saline is used for the ventricular muscle 
because it increases the rhythmicity to a degree convenient for study. 


In pure serum or blood the rhythmicity is entirely absent though it is 
significant that the few sporadic contractions that do occur are large. 

This preparation makes possible many instructive experiments tending 
to show fundamental properties of cardiac muscle. The preparation 
contains no nervous mechanism except terminal fibers, and its behavior 
may be safely attributed to the muscle substance itself. 

Try the following experiments: i. Submit the strip to saline solutions 
of different temperatures, varying through steps of 10 degrees from o C. 
to 30 C. 2. Try the effect of the different ingredients in Ringer's solution 
using physiological saline as the standard normal for the ventricle, see Exp. 
6, b, c, etc. 

a. Combine potassium chloride with saline, figure 172; 

b. Calcium chloride with saline, figure 173; 

c. Potassium and calcium chloride and saline; 

d. Locke's solution; 

e. Solution of blood diluted with saline; 

/. Solution of milk with saline in the proportion of one part milk to 
four of saline. 

Cut and mount strips from the auricle and from the sinus, letting the 
latter extend out on to the vena cava. In these last preparations care 
must be taken to balance the lever, as a slight overtension paralyzes the 

Immerse these strips in pure serum, or Ringer but not physiological 
saline, and compare their behavior with that of the ventricle in pure serum. 
The sinus and usually the auricle will be found rhythmic in serum, while 
the ventricle, if it contracts at all, will contract at irregular periods. 
Often there is a distinct progressive decrease in the rhythm, the sinus 
having the same rhythm as the whole heart, the auricle a considerably 
slower rhythm, and the ventricle slow and aperiodic. The sinus prepa- 
ration will show beside the fundamental rhythm a characteristic slow 
contraction and relaxation, which has been described as tone, figure 170. 
Repeat Exp. 6, a, b } c, etc., on the auricle and sinus. 

ii. Influence of the Cardiac Nerves on the Frog's Heart. Care- 
fully pith a frog with the minimal loss of the blood of the animal. Expose 
the heart as previously described, make a cut through the manubrium, 
continue it through the skin and muscles at the angle of the jaw, thus 
exposing the vagus nerve. The vagus runs along the edge of a delicate 
muscle diagonally downward and backward toward the heart. The 
glosso-pharyngeal is just in front of the vagus and the hypoglossal just 
behind it. The latter runs parallel with the vagus near its origin, but 
lower down turns across the vagus and runs to its distribution in the 
tongue muscles. These two nerves serve to aid the student in the identi- 
fication of the vagus, see figure 217. It is usually better to cut the 


hypoglossal away, and also to cut the brachial and the laryngeal nerves 
to prevent the stimulation of undesired structures. 

FIG. 216. Arrangement of Apparatus for Studying the Contractions of the Strip of the 

Apex of the Ventricle. 

Prepare an induction coil, see laboratory experiments on muscle. Use 
platinum electrodes of the Harvard pattern, set the coil for a mild stimulus 
tested by the lips or the tongue, 
lift up the vagus gently and lay 
it on the platinum tips of the 
electrodes. Take care that the 
electrodes do not come in contact 
with the adjacent tissue. Arrange 
a signal magnet as shown in the 
diagram, so that the magnet and 
the stimulating key of the induc- 
tion coil may be closed and opened 
at the same instant. When all is 
ready (a) secure a normal record, 
then (b) stimulate the vagus for 
five to ten seconds, recording the 
time with the signal magnet and 
allowing the record to continue 

until the heart has returned to its 

i T. j FIG. 217. Diagram Showing the Rela- 

normal rate and amplitude, -I.e., tions of the f vago-sympathetic Nerve to the 

Hy, Hypoglossal; Gl, 
V, vago- 

usually one circuit of the drum. Heart, in the Frog. 
Most students fail in this experi- 
ment by 'not allowing sufficient 
time in the record for a normal before stimulation, and by not allowing 


sufficient time after stimulation for a return to the normal. It will be 
better to take one good tracing, showing all the facts of the experiment, 
than several partial tracings, none of which are complete. 

With these suggestions in mind, (c) repeat the above experiment, 
using stimulating currents of increasing intensity until complete cardiac 
inhibition is produced, (d) Perform experiments showing the influence 
of the duration of the stimulation on the inhibition; i.e., stimuli of i 
second, 2 seconds, 10 seconds, and 30 seconds. 

In the frog the vagus, or inhibitory, and sympathetic, or accelerator, 
fibers, are found in one trunk, the vago -sympathetic, but stimuli will usually 
produce inhibitions and not acceleration. Occasionally with very weak 
preparations direct acceleration may be produced. To get the pure 
inhibitory or pure accelerator effects one must dissect back to and (e) 
stimulate the trunk of the vagus before it is joined by the sympathetic 
fibers; or to the sympathetic trunk and (/), stimulate between the third 
spinal nerve and the point where it joins the vagus trunk. Pure accelera- 
tor effects may be demonstrated by (g), stimulating the vago-sympathetic 
after applying i c.c. of o.i per cent, atropine to the heart to poison the 
vagus endings, (ti) perfusion of i c.c. of o.oi per cent, epinephrin will 
chemically stimulate the accelerator endings in the presence of normal 
vagus endings. 

In the study of the above experiments one should note the rates per 
minute and the amplitude of the normal period just before stimulation r 
the rate and amplitude during the period of stimulation, and the same 
at different times after the stimulation until constant results are obtained. 
A tabulation of these results will usually enable one to judge the influence 
of each of the various factors recommended in the experiment. 

12. Influence of the Cardiac Nerves on the Terrapin's Heart. 
Instead of the frog one may use the terrapin in the above experiment. 
In this animal the vagus and sympathetic in the neck- can very readily be 
isolated. It is usually quite impossible to demonstrate any cardiac accel- 
eration. But the vagus produces inhibitions which differ from the effects 
in the frog in that during the recovery from complete inhibitions the 
ventricular contractions are apparently at once maximal, see figures 180 
and 181. In the frog the ventricular contractions when they reappear 
are at first slight, but gradually increase in amplitude until they have 
their former value. The student should explain the significance of these 

13. Arterial Blood-pressure in Man. The arterial blood-pressure in 
man can be measured indirectly by measuring the pressure which it 
takes around the arm completely to close the artery. Some form of the 
Riva-Rocci type of apparatus, preferably the Tyco or Faught, should be 
used. Two points fundamental to physiology and to clinical diagnosis can 
be determined, the systolic or maximum pressure in the artery, and the 
diastolic or minimum pressure. 


a. Bare the left arm, and wrap the rubber sleeve band snugly just 
above the elbow and turn the free end under at the top. Connect the 
Tyco or Faught manometer with one entrance tube and the bulb pump 
with the other. 

Lightly bind the bell of a stethoscope over the brachial artery on the 
inner surface of the forearm just under the border of the arm band. 

b. Quickly fill the band to a pressure of 150 mm., i.e., completely com- 
press the brachial artery. Slowly allow the air to escape, listening care- 
fully with the stethoscope for the first appearance of a pulse murmur in 
the artery. At the same time watch for the appearance of oscillations 
in the dial of the manometer. At a certain pressure the hand of the dial 
will suddenly begin to oscillate and a distinct intermittent sound clear 
and sharp in tone will be heard. This is the moment when the first escape 
of blood through the compressed artery takes place. It measures the 
systolic pressure, c. Continue to reduce the pressure. The oscillations 
of the dial will increase up to a certain point. An intermittent pulse will 
be heard passing into a loud and sharp snappy sound. At a certain 
point the sound suddenly becomes dull and low and disappears. The 
point of maximum oscillation and of disappearance of the intermittent 
sound marks the diastolic pressure. 

Measure the pressures in the standing position, in sitting position, 
and after a short run. Tabulate the results and draw averages. Repeat 
the measurements on children and elderly people, using care not to pro- 
long the total compression of the artery. 

14. The Arterial Blood-Pressure in a Mammal. The arterial blood- 
pressure may be measured on the anesthetized cat, dog, or rabbit. Simple 
blood-pressure was originally measured by Hale's method of connecting 
the artery with a vertical tube and allowing the blood to flow freely into 
the tube until a column was raised to the height which balanced the pres- 
sure in the vessel. This simple method is decidedly the best for the 
beginner, since it does not necessitate the use of very complicated appara- 
tus. At the same time it gives practice in anesthesia and in operations 
under anesthetics, and therefore serves as a good preparation for the more 
complicated experiments which follow. 

The necessary apparatus should first be prepared as follows : A vertical 
tube supported on a stand with a scale graduated in the metric system, 
assorted cannulae of approximately the size of the carotid artery of the ani- 
mal to be operated on, linen-thread ligatures, dissecting set in good condition, 
an animal-holder with strings or straps firmly to fasten the anesthetized 
animal, a chloroform-ether mixture for dogs (or other anesthetic according 
to the animal to be used). Four men should be assigned to perform this 
experiment. While two are chloretonizing, anesthetizing and preparing 
the animal, two should arrange the apparatus as nearly ready for con- 


necting with the artery as possible. When all the apparatus is arranged 
and the animal anesthetized, it should be tied firmly to the animal-holder. 
Let one experimenter attend strictly and at all times to anesthetizing the animal; 
recovery to light anesthesia must not occur. Let the operator quickly expose 
about 3 cm. of the carotid artery (or the femoral artery if circulation time 
is also to be tested on this animal), by making an incision through the skin 
of the neck 5 cm. long, and dissecting down between the muscles. Sepa- 
rate the carotid from the adherent vagus nerve by tearing the connective 
tissue with the scalpel handle, freeing the vessel for about 2 to 3 cm. of its 
length. Lay two loose ligatures of linen thread around the vessel, place 
a small bulldog forceps on the exposed artery nearest the heart, and ligate 
the end nearest the head with one of the ligatures. Lift up the inter- 
vening artery with strong forceps and make a V-shaped cut near the liga- 
ture pointing the cut toward the heart, let it extend about half-way across 
the artery. Introduce a cannula toward the heart, and tie it firmly with 
the second ligature. Connect the cannula with the rubber tubing to 
the vertical glass tube. 

When all is ready remove the bulldog forceps from the artery. The 
blood will flow freely from the artery into the tube, rising by rapid spurts 
until the pressure from the column of liquid is just equal to that inside 
the artery itself. If an anticoagulant-like powdered potassium oxalate 
is first introduced into the vertical tube, probably clotting at the cannula 
will be delayed for some minutes. The mounting of the blood into the 
empty tube makes, indeed, a most striking demonstration. 

An accurate measure of the height of the top of the column above the 
level of the cannula at the artery represents the arterial blood-pressure in 
terms of blood. The specific gravity of blood is 1.056; of mercury, 13.6. 
Record the pressure you obtain in terms of blood and of mercury. Note 
also the variations in pressure and account for the rhythm of each. 
There will be a general variation of pressure, depending upon the degree 
of anesthesia. If anesthesia is light and muscular movements happen, 
there will be an increase in the blood-pressure. If the anesthesia is 
heavy, then the blood-pressure falls. These points of variation should 
be marked and recorded at once in note-books. Make full notes of all 
accessory facts which would aid in explaining the variations in blood- 
pressure, such as size of the animal, rate of respiration, rate of heart-beat, 
the variations in anesthesia, the presence of the reflexes, etc., etc. 

Chloroform the animal to kill it, and note the change in blood-pressure 
during the process, but first do experiment 15. 

15. The Circulation Time. The circulation time is most satisfactorily 
determined in the laboratory by introducing a saline solution of methylene 
blue into the jugular vein on one side. Note the exact time with a stop- 
watch until the color appears in the carotid artery, and in the jugular 
vein of the opposite side. 


Anesthetize a cat or dog with a chloroform-ether mixture, tie it on the 
animal-holder and, when the eye reflexes are lost, expose the jugular vein 
on the right side, the carotid artery and the jugular vein on the left. Fill a 
2-cm. hypodermic syringe with i per cent, methylene blue in physiological 
saline, insert the needle into the right jugular vein, pointing it toward the 
heart. Lift the left carotid artery and place under it a strip of moist white 
paper 2 cm. wide; prepare the left jugular vein in the same way. Place the 
animal so that these vessels are lighted to the best advantage. At a given 
moment inject the contents of the hypodermic syringe, noting the time 
with a stop-watch. Observe the color of the left carotid and the left 
jugular, respectively, very carefully, and take the time of the first appear- 
ance of the methylene blue. The color will appear first in the artery, 
second in the vein. The difference in time between the moment of injec- 
tion and the moment of color in the artery represents, with a slight cor- 
rection, the circulation time of the pulmonary or lesser circulation. The 
time from the injection until the color in the other jugular vein represents 
the total time of circulation. 

Stewart has made these determinations even more correctly by the elec- 
trical-resistance method. He injected 10 per cent, salt solution and deter- 
mined the variation in resistance by a galvanometer. If the galvanometer 
is available, then check the above determinations by the electrical method, 
arranging the apparatus under the direction of an instructor. 

1 6. The Blood -pressure Model. An artificial model of the circulatory 
apparatus, which illustrates all mechanical parts involved, has been 
arranged by Porter, or can be easily constructed. The model should 
have the following possibilities: A pump, which permits of rhythmic 
action at a varying rate and varying force; a resistance to the outflow 
liquid which can be increased or decreased; and an elastic set of vessels 
into which the pump discharges. 

If Porter's schema is used, determine the following points, (a) The 
pressure in terms of mercury in the arterial and venous limbs of the 
apparatus when the pump makes a rate of 72 per minute; (b) the influence 
on these two pressures when the rate is increased, when it is decreased, 
(c) the effect on these pressures when the peripheral resistance is great, 
when it is low. With a sphygmograph, (d) take a tracing of the pulse in 
the elastic tube representing the arterial side of the schema. 

If an ordinary bulb syringe and simple apparatus is used, then deter- 
mine the following: (e) The character and rate of the outflow when water 
is pumped into the rigid glass tube with no resistance to the outflow; (f) 
when a glass tube of smaller caliber is connected with the end of the larger 
glass tube so as to produce a high resistance to the outflow, (g) Pump the 
water into a rubber tube of smaller size and compare with the proceeding 
when there is no resistance to the outflow; also (/?) when a glass tube of 


small caliber is introduced into the end in order to produce high resistance 
to the outflow. Determine the amount of resistance necessary to produce 
a constant outflow when the pump has a rate of 72 beats per minute. 

In this experiment what effect is produced on the outflow if the rate 
of the pump is varied? if the force of the stroke is varied? if the elasticity 
of the rubber tube representing the artery is varied? If the resistance 
represented by the size of the glass tube at the outflow is varied? 

17. The Arterial Pulse. The form of the arterial pulse maybe taken 
by one of the various sphygmographs applied to the radial artery at the 
wrist or the common carotid in the neck. If the tambour method is used, 
apply a sphygmographic tambour on the wrist adjusting the central 
pressure over the radial artery. Fasten it in place by the proper bands, 
adjusting the tension by flexing the wrist. Connect the receiving tambour 
with a delicately balanced, small-sized recording tambour, which should 
write its movements on a cylinder revolving at the rate of i to 2 cm. per 

A convenient clinical instrument is the Dudgeon or the Jacquet 
sphygmograph. These are to be applied at the wrist and give tracings 
showing delicate variations in the form of the pulse wave with great 
magnification and a considerable degree of accuracy. Make a comparison 
of the form of the pulse wave from tracings taken from at least six different 

The sphygmogram from the carotid artery may best be taken by 
applying an air sphygmograph to the neck over the carotid and fastening 
it in position by a spring. Record by the tambour method. 

1 8. The Rate of Propagation of the Pulse Wave. Apply tambour 
sphygmographs to the carotid in the neck and to the radial at the wrist, and 
make simultaneous records on a drum, adjusting the writing levers 
of the two recording tambours in an exact vertical line. Let the recording 
drum travel at the speed of 2 cm. or more per second, and record the speed 
by a 50 double-vibration tuning-fork. The carotid pulse will be found to 
precede the radial pulse by the fraction of a second. This short interval, 
which can be determined in thousandths of a second by comparison with 
the time tracing below, represents the time required for the pulse wave to 
traverse the distance from the carotid to the radial. Measure the distance 
used in the experiment and calculate the rate of propagation in centi- 
meters per second. 

If the writing points of the recording levers in this experiment are made 
of very delicate strips of note paper or of thin photographic film celluloid, 
so as to offer little resistance to the surface of the drum, the detail of the 
pulse wave at the two points will be accurately transcribed and may be 

19. The Capillary Circulation. The capillary circulation is best 


demonstrated in the laboratory by direct observation on the web of the 
frog's foot by the use of the compound microscope. Give a 4o-gm. frog a 
hypodermic injection of 0.3 c.c. of ether under the skin of the back. Wet 
a piece of cheesecloth the size of a handkerchief with tap water and wrap 
the etherized frog so as to cover the entire body with the exception of the 
foot. When the anesthesia has progressed so as to destroy voluntary 
movements, bind the foot on an ordinary frog board and spread the web 
over the window in the board. Choose an area of the skin which shows 
small arteries, capillaries, and veins, and in which the blood is flowing 
freely and rapidly. Examine with the low-power of a compound micro- 
scope. In a favorable field small arteries, capillaries, and veins with 
blood flowing rapidly through them will be easily found. Choose one 
such field, cover with a piece of thin cover-glass, moisten with a drop 
of water if necessary, and examine with a high power. Note in the small 
artery the pulsating current; the border of clear fluid along the side of the 
main stream of blood; the white corpuscles along the clear borders of the 
current. In the small veins there are usually no pulsations and the speed 
of the current is somewhat less. Careful examination of the capillaries 
will reveal a delicate wall, the individual corpuscles, and the fact that the 
red corpuscles are actually larger than the diameter of the capillary at 
some points and must be bent to pass through. Note that the capillaries 
form an intricate and anastomosing network; that the current may occa- 
sionally be reversed in some of the anastomoses. 

The anesthetizing effect of the ether recommended will usually con- 
tinue about 10 to 20 minutes. If the observation is more prolonged, a 
second dose of ether should be given. The capillaries in the tails of small 
fish are often very readily observed, and these may be substituted for the 
frog's web. 

20. Capillary Blood-Pressure of Man. Measure the capillary blood- 
pressure in your own finger by von Krie's method. This apparatus con- 
sists of a small piece of glass an inch square, or less, which is placed across 
the knuckle of the finger just back of the nail. A small weight pan is 
suspended by a loop of thread over this glass plate so that weights put in 
the pan will bring varying pressure on the plate above. Add weights to the 
pan until an area of the skin, about 5 mm. in diameter, is blanched by the 
pressure. Mark the outline of this bloodless area on the glass, take 
off the apparatus and measure the exact area of the glass so marked, weigh 
the entire apparatus and compute the pressure in grams per square centi- 
meter for the area. This pressure in terms of mercury represents the 
capillary blood-pressure in the vessels of the skin of the finger at that 
level. Measure the pressure when the finger is held at the level of the top 
of the head; with the finger held as low as possible; held at the level of the 
heart. Tabulate the measurements. The capillary blood-pressure at the 
level of the heart is usually from 40 to 50 mm. of mercury. 


Lombard determines the end point in this experiment more accurately 
by the aid of a low power binocular microscope after rubbing vaseline into 
the skin to increase its transparency. Hooker's method of compressing 
the capillaries by an air system controlled and measured by a manometer 
allows measurement both during compression and in decompression. This 
method has been adapted to the mammalian mesentery by Ellis. 

21. The Arterial Blood -Pressure in a Mammal and Its Nervous 
Regulation. After the student has measured the arterial blood-pres- 
sure by Hale's method, described above, he is in a position to study the 
variations and co-ordinations in the blood circulatory apparatus. The re- 
cording apparatus consists of writing pens, seconds time marker, signal 
marker, blood-pressure manometer preferably Ludwig's mercury manom- 
eter, and a continuous paper kymograph preferably Ludwig's weight- 
driven form or the Harvard belt kymograph for a continuous record of the 
arterial blood-pressure. Connect the cannula with the mercury man- 
ometer which is provided with a pressure bottle. Use a cannula of the 
form shown in figure 185, connecting the side limb of the cannula with the 
mercury manometer, and the end limb with the pressure bottle. When 
the apparatus is ready chloretonize and anesthetize a mammal (dog, cat, or 
rabbit), and bind it to the animal-holder. Let one operator attend strictly 
and at all times to the anesthetic, for the animal must not under any condition 
recover consciousness during the experiment. 

Expose the carotid artery in the neck, as described in Experiment 13 
above, arrange it with ligatures for inserting the cannula, expose the 
vagus nerve with the same care, and throw ligatures around it for con- 
venience in lifting it out of its bed. Make a V-shaped cut in the carotid 
directed toward the heart, insert and ligate the cannula as previously 
described. Before beginning the experiment one should see that all the 
tubes are filled with the anticoagulating liquid and that the manometer is 
under pressure from 130 to 140 mm. mercury. When all is ready start the 
kymograph, see that the recording pens are properly adjusted, remove the 
bulldog forceps from the artery, and the pressure record will begin. 

a. Take a tracing of the normal arterial pressure and heart rhythm with 
the recording paper moving at the rate of 0.5 cm. per second. 

b. Stimulate the right vagus nerve with a mild induction current for 
10 seconds. If this stimulus is strong enough to produce change in blood- 
pressure or inhibitions of the heart-rate, then allow sufficient time follow- 
ing the stimulus for the blood-pressure to return to the previous normal. 
Observing these rules, vary the intensity of the stimulus from that which 
produces no apparent effect to that which produces complete inhibition of 
the heart. Vary the time of the stimulus through i, 5, io,and 20 seconds, 
using different strengths. Do not allow the nerve to cool, become dry, 
or to be unduly stretched. 


c. Test the sensitiveness of the left vagus. 

d. Allow the vagus to fall back in its warm bed and stimulate the skin 
of the animal at some sensory surface, say the lips, the ear, or the foot. 
By varying the intensity of the stimulus, a strength will be found which 
will produce no reflexes of the voluntary muscles, but will produce marked 
effects on the heart rate and on the blood-pressure. 

Expose the sciatic nerve, or any other nerve trunk containing afferent 
or sensory fibers, cut it, and stimulate the central end for five seconds. 
With a proper strength of stimulus a greater effect is produced on the 
heart and on the blood-pressure than by stimulating a small spot of skin. 
This stimulus will also reflexly accelerate respiration. 

e. Cut the right vagus nerve and mark the exact time on the tracing by 
the signal marker. Do not disturb the animal of the record until stable 
equilibrium is again reached. 

/. Now lift up the distal end of the divided right vagus, and stimulate 
it with the strength which previously just produced inhibition. Repeat 
the experiment on the proximal end of the divided vagus. The reflex 
effects are still threefold, cardiac, vasomotor and respiratory. The stimu- 
lation of the proximal end of the vagus produces effects on the heart rate 
when one vagus is still intact. See Experiment / below. 

g. After 10 to 15 seconds cut the left vagus, marking the time of cutting 
on the tracing with the same care as before. As soon as the vagus nerves 
are cut, the heart-rate will be observed to increase sharply and the blood- 
pressure to rise. The respirations also change in rate and depth, a fact 
which can be noted directly and by its influence on the blood-pressure 

h. Lift up the distal end of the left vagus, and stimulate it with an 
electric current of the strength which previously just produced inhibition. 
Stimulate the proximal end of the divided vagus. The stimulation 
produces no direct inhibitory effect on the heart rate when both vagi are 
cut, but does produce profound changes in the blood-pressure owing to 
vaso-motor reflexes. 

Occasionally an animal will be found in which one or both vagi are 
comparatively inactive. 

k. If the rabbit is used, stimulate the depressor nerve, which produces 
a marked fall in blood-pressure from reflex effects, explain. 

/. Repeat the stimulation of the central end of the sciatic as described 
in /, now that the vagus nerves are cut. The stimulation of this nerve 
no longer produces decrease in the heart-rate, but occasionally an accelera- 
tion. The blood-pressure is influenced as before, showing that the vaso- 
motor centers are reflexly stimulated. 

m. When you have finished the outline of experiments, give an excess 
of ether to kill the animal and continue the record until it is dead. The 


blood-pressure will fall rapidly, the heart-rate will become slower but 
does not cease for a long time after respirations stop. 

Should a clot form in the cannula, put a bulldog forceps on the artery, 
disconnect the manometer tube, and wash the clot out by a stream of 
liquid from the pressure bottle. Use care not to allow this fluid to enter 
the exposed wound. 

Represent the results of each individual experiment in the above series 
in tabulated form which shall show: i, the blood-pressure and heart-rate 
just before each experiment; 2, during the experiment; and 3, at different 
times after the experiment until the normal is reached. After the data 
are taken from the tracings and arranged in tabular form, make a study 
of these facts and draw all the conclusions you can concerning the nervous 
regulations of the heart and of the blood-pressure. Make a written report. 

2 2 . The Vaso-motor Changes in the Finger, the Plethysmogram. Insert 
the ringer in the Porter ringer plethysmograph, fill the tube with warmed 
water, and connect it with a small-sized air tambour. The variations in 
volume of the finger are slight, so that one must use a most delicate 
recorder. Take a tracing at a slow speed, i mm. per second. The finger 
and its plethysmograph should be suspended so that no mechanical 
movements will destroy the accuracy of the record. Observations through 
several minutes will usually show variations in volume of the finger, 
which will be recorded by the tambour. The reagent must be warm 
and relaxed. 

Try a short mental problem. Cold air or cold water in the face will 
usually be marked by a decrease in volume indicating vaso-constriction. 
Warmth will lead to increase in volume indicating vaso-dilatation. In 
sleep there is the greatest relaxation and a large volume pulse will be 

23. The Vaso-motors of the Frog's Web. Prepare a frog for observa- 
tion of the circulation of the web under the microscope, as described above, 
giving it 3 drops of ether, or just enough i per cent, curare to destroy 
voluntary movements. Quickly dissect the sciatic nerve in the thigh, 
using extreme care not to interfere with the circulation. Mount the 
preparation, pick out an active field of capillaries, small arteries, and 
veins under the low power of the microscope, then adjust the high power 
to a field which shows one or more small arteries. Make a drawing to 
record the diameter of these arteries, using pigment cells for land-marks, 
or measure with an ocular micrometer. Now quickly stimulate the 
exposed sciatic nerve while keeping the selected artery under constant 
observation. After stimulation for 10 seconds the diameter of the vessels 
will be seen to decrease considerably, sometimes to the point of complete 
occlusion. When the stimulation ceases, the vessel will remain contracted 
for a few seconds, then will slowly regain its usual caliber, figure 201. 


This is an exceptionally good method for direct observation of the vaso- 
motor changes. 

24. The Plethysmogram of the Kidney. Anesthetize a dog or cat, 
see Experiments 12 and 19 above, and take continuous blood-pressure 
tracings. Now open the abdominal wall by an incision along the median 
line, expose the left kidney and carefully dissect off its capsule, taking 
care not to injure its artery and vein. Enclose the kidney in the renal 
onkometer and carefully seal with vaseline and cover with omentum. 
Connect it with a delicate volume recording apparatus. Brodie's bellows 
recorder or a large air tambour is the best for this purpose. Adjust the 
recording apparatus in the vertical line with the manometer and signal 

Stimulation of the nerves which affect general blood-pressure through 
the medium of the heart will produce changes in the volume of the kidney 
in the same direction as the blood-pressure. Stimuli which give varia- 
tions of the blood-pressure without direct change in the heart itself affect 
the volume of the kidney independent of the blood-pressure : 

a. Dissect out and stimulate the splanchnic nerves just where they 
pass through the pillars of the diaphragm. They cause vaso-constriction 
in the kidney without sharply affecting the blood-pressure. 

b. Stimulate the depressor nerve, or the central end of the divided 
vagus. The volume of the kidney will increase though the general blood- 
pressure decreases, showing that the fall of blood-pressure is due to 
peripheral vascular dilatation. 

c. Stimulate the peripheral end of the divided vagus so as to slow or 
even completely to stop the heart. The sharp fall in blood-pressure is now 
accompanied by decrease in the volume of the kidney, showing that the 
kidney volume is merely passively following the blood-pressure. 


THE maintenance of animal life necessitates the continual absorption of 
oxygen and the excretion of carbon dioxide by the living tissues. The blood 
is the medium in all animals which possess a well-developed blood-vascular 
system by which these gases are carried. Oxygen is absorbed by the blood 
from without and conveyed to all parts of the organism; and carbon dioxide 
which comes from the cells within is carried by the blood to the surfaces 
from which it may escape from the body. The two processes absorption 
of oxygen and excretion of carbon dioxide are complementary, and their 
sum is termed the process of Respiration. 

In all Vertebrata and in a large number of Invertebrata certain parts, 
either lungs or gills t are especially constructed for bringing the blood into 
proximity with the aerating medium (atmospheric air, or water containing 
air in solution). In some of the lower Vertebrata (frogs and other naked 
Amphibia) the skin is important as a respiratory organ, and is capable of 
supplementing to some extent the functions' of the proper breathing 

A lung or a gill is constructed essentially of a fine transparent membrane, 
one surface of which is exposed to the air or water, as the case may be, while 
on the other surface is a network of blood vessels. The only separation be- 
tween the blood and aerating medium is the thin wall of the blood vessels 
and the thin membrane on which the vessels are distributed. The difference 
between the simplest and the most complicated respiratory membrane is 
one of degree only. 

In the mammals and the higher vertebrates the respiratory membrane 
is included within a respiratory cavity, the chest or thorax, which carries on 
regular movements, the respiratory movements, to bring changes of air into 
close contact with the respiratory surface. 

The complexity of the respiratory membrane, the kind of aerating me- 
dium, and the respiratory movements are not, however, the only conditions 
which cause a difference in the respiratory capacity of different animals. 
The quantity and composition of the blood, especially as regards the number 
and size of the red corpuscles, and the vigor and efficiency of the circulatory 
apparatus in driving the blood to and fro between the lungs and the active 
tissues, these are conditions of equal, if not greater, importance. 

It may be as well to state here that the lungs are only the medium for the 
exchange, on the part of the blood, of carbon dioxide for oxygen. The 




living tissues are the seat of those combustion processes which consume 
oxygen and produce carbon dioxide. These processes occur in all parts of 
the body in the substance of the living active tissues, and are the true respira- 
tory processes, sometimes called internal or tissue respiration. 


The object of the respiratory movements being the interchange of gases 
in the lungs, it is necessary that the atmospheric air shall pass into them 
and that the changed air shall be ex- 
pelled from them. The lungs are 
contained in the chest or thorax, which 
is a closed cavity having no communi- 
cation with the outside except by 
means of the respiratory passages. 
The air enters these passages through 
the nostrils or through the mouth, 
thence it passes through the larynx 
into the trachea or windpipe, which 
about the middle of the chest divides 
into two tubes, the bronchi, one to 
each lung. 

The Larynx. The upper part of 
the passage which leads exclusively 
to the lung is formed by the thyroid, 
cricoid, and arytenoid cartilages, 
figure 218, and contains the vocal cords, 
by the vibration of which the voice is 
chiefly produced. These vocal cords 
are ligamentous bands covered with 
mucous membrane and attached to 
certain cartilages which are capable of 
movement by muscles. By their ap- 
proximation the cords can entirely 
close the entrance into the larynx; but 
under ordinary conditions the entrance 
of the larynx is formed by a more or 
less triangular opening between them, 
called the rima glottidis. Projecting 
at an acute angle between the base of 
the tongue and the larynx to which it 

is attached, is a leaf- shaped cartilage the trachea, showing sixteen cartilaginous 
. - ^. . rings; b, the right, and b', the left bronchus. 

FIG. 218. Outline Showing the General 
Form of the Larynx, Trachea, and Bronchi, 
as seen from Before, h, The great cornu 
of the hyoid bone; e, epiglottis; /, superior, 
and t r , inferior cornu of the thyroid carti- 
lage; c, middle of the cricoid cartilage; tr, 

.,,._,, . - ^. . 

with its larger extremity free. This 

(Allen Thomson.) 



is called the epiglottis. The whole of the larynx is lined by mucous mem- 
brane, which, however, is extremely thin over the vocal cords. At its lower 
extremity the larynx joins the trachea. 

Taste buds have been found in the epithelium of the posterior surface of 

the epiglottis, and in several other 
situations in the laryngeal mucous 

The Trachea and Bronchi. 
The trachea extends from the 
cricoid cartilage, which is on a 
level with the fifth cervical vertebra, 
to a point opposite the third dorsal 
vertebra, where it divides into the 
two bronchi, one for each lung, 
figure 218. The trachea measures, 
on an average, four or four and a 
half inches, 12 to 14 cm., in length, 
and from three-quarters of an inch 
to an inch, 2 to 2.5 cm., in diameter, 
and is essentially a tube of fibro- 
elastic membrane within the layers 
of which are enclosed a series of 
cartilaginous rings, from sixteen to 
twenty in number. These rings 
extend only around the front and 
sides of the trachea, about two- 
thirds of its circumference, and 
are deficient behind; the interval 
between their posterior extremities 
being bridged over by a continua- 
tion of the fibrous membrane in 
which they are enclosed, figure 
219, h. 

Immediately within this tube and 

FIG. 219. Section of the Trachea, a, 
Columnar ciliated epithelium; 6, and c, 
proper structure of the mucous membrane, 
containing elastic fibers cut across trans- 
versely; d, submucous tissue containing 
mucous glands, e, separated from the hya- 
line cartilage, g, by a fine fibrous tissue,/, h, 
external investment of fine fibrous tissue. 
(S. K. Alcock.) 

at the back is a layer of unstriped 
muscular fibers. This muscular layer extends transversely between the 
ends of the cartilaginous rings to which it is attached, and also opposite the 
intervals between them; its evident function being to diminish the caliber 
of the trachea by approximating the ends of the cartilages. Outside there 
are a few longitudinal bundles of muscular tissue, which, like the preceding, 
are attached both to the fibrous and to the cartilaginous framework. 

The mucous membrane, figures 219 and 220, consists largely of adenoid 
tissue, separated from the stratified columnar epithelium , which lines it, by a 



homogeneous basement membrane. This is penetrated here and there by- 
channels which connect the adenoid tissue of the mucosa with the inter- 
cellular substance of the epithelium. The stratified columnar epithelium 
is formed of several layers, of which the most superficial layer is ciliated and 

FIG. 220. Ciliary Epithelium of the Human Trachea, a, Layer of longitudinally 
arranged elastic fibers; &, basement membrane; c, deepest cells, circular in form; d, inter- 
mediate elongated cells; e, outermost layer of cells fully developed and bearing cilia. X 
350. (Kolliker.) 

the cells often branched downward. Many of the superficial cells are of the 
goblet variety. In the deeper part of the mucosa are many elastic fibers 
between which lie connective-tissue corpuscles and capillary blood vessels. 

Numerous mucous glands are situated on the exterior and in the substance 
of the fibrous framework of the trachea, their ducts perforating the various 

FIG. 221. Transverse Section of a Bronchus, about $ inch in Diameter, e, Epithelium 
(ciliated); immediately beneath it is the mucous membrane or internal fibrous layer, of 
varying thickness; m, muscular layer; s, m, submucous tissue;/, fibrous tissue; c, cartilage 
enclosed within the layers of fibrous tissue; g, mucous gland. (F. E. Schulze.) 

structures which form the wall of the trachea, and opening through the 
mucous membrane into the cavity of the trachea. 

The two bronchi into which the trachea divides resemble the trachea 
in structure, with the difference that in them there is a distinct layer of un- 
striped muscle arranged circularly beneath the mucous membrane, forming 


the muscularis mucosa. On entering the substance of the lungs the carti- 
laginous rings, although they still form only larger or smaller segments of 
a circle, are no longer confined to the front and sides of the tubes, but are 
distributed impartially to all parts of their circumference. 

The bronchi divide and subdivide in the substance of the lungs into 
smaller and smaller branches, which penetrate into every part of the organ 
until at length they end in the smaller subdivisions of the lungs called 

All the larger branches have walls formed of tough membrane, contain- 
ing portions of cartilaginous rings, by which they are held open, and un- 
striped muscular fibers, as well as longitudinal bundles of elastic tissue. 
They are lined by mucous membrane, the surface of which, like that of the 
larynx and trachea, is covered with ciliated epithelium; but the several 
layers become less and less distinct until the lining consists of a single layer 
of more or less cubical cells covered with cilia, figure 221. The mucous 
membrane is abundantly provided with mucous glands. 

As the bronchi become smaller and smaller and their walls thinner, the 
cartilaginous rings become fewer and more irregular, until in the smaller 
bronchial tubes they are represented only by minute and scattered cartilag- 
inous flakes. And when the bronchi by successive branches are reduced 
to about -fa of an inch, 0.6 mm., in diameter, they lose their cartilaginous ele- 
ment altogether and their walls are formed only of a tough, fibrous, elastic 
membrane with circular muscular fibers. They are still lined, however, 
by a thin mucous membrane with ciliated epithelium, the length of the 
cells bearing the cilia having become so far diminished that the cells are 
almost cubical. In the smaller bronchi the circular muscular fibers are 
relatively more abundant than in the larger bronchi and form a distinct 
circular coat. 

The Lungs and Pleurae. The lungs occupy the greater portion of 
the thorax. They are of a spongy elastic texture, and on section appear 
to the naked eye as if they were in great part solid organs, except where 
branches of the open bronchi or air-tubes may have been cut across and show 
on the surface of the section. In fact, however, the lungs are hollow organs 
composed of a mass of air cavities all of which communicate finally with 
the common air-tube, the trachea. 

Each lung is enveloped by a serous membrane, the pleura, which ad- 
heres closely to its surface and provides it with its smooth and slippery 
covering. This same membrane lines the inner surface of the chest wall. 
The continuity of this membrane, which forms a closed sac as in the case 
of other serous membranes, will be best understood by reference to figure 222. 
The appearance of a space, however, between the pleura which covers the 
lung, visceral layer, and that which lines the inner surface of the chest, parietal 
layer, is inserted in the drawing only for the sake of distinctness. These 


layers are, in health, everywhere in contact, one with the other; and between 
them is only just as much fluid as will insure frictionless movement in their 
expansion and contraction. 

When considering the subject of normal respiration, one may discard 
altogether the notion of the existence of any space or cavity between the 
lungs and the wall of the chest. If, however, an opening be made so as to 
permit air or fluid to enter the pleural sac, the lung in virtue of its elasticity 
recoils, and a considerable space is left between it and the chest wall. In 
other words, the natural elasticity of the lungs would cause them at all times 
to contract away from the ribs were it not that the contraction is resisted by 
atmospheric pressure which bears only on the inner surface of the air-tubes 
and air-cells. 

The pulmonary pleura consists of an outer or denser layer and an inner 
looser tissue in which there is a lymph-canalicular system. Numerous 

FIG. 222. Transverse Section of the Chest. 

lymphatics are to be met with, which form a dense plexus of vessels, many 
of which contain valves. They are simple endothelial tubes, and take origin 
in the lymph-canalicular system of the pleura proper. Scattered bundles 
of unstriped muscular fiber occur in the pulmonary pleura. They are es- 
pecially strongly developed on the anterior and internal surfaces of the lungs, 
the parts which move most freely in respiration. Their function is doubt- 
less to aid in expiration. 

The Finer Structure of the Lung. Each lung is partially subdi- 
vided into separate portions called lobes: the right lung into three lobes 
and the left into two. Each of these lobes, again, is composed of a large num- 
ber of minute parts, called lobules. Each pulmonary lobule may be con- 
sidered to be a lung in miniature, consisting, as it does, of a branch of the 
bronchial tube, of air-cells, blood vessels, nerves, and lymphatics, with a 
small amount of areolar tissue. 


On entering a lobule, the small bronchial tube, the structure of which 
has just been described, a, figure 223, divides and subdivides; its walls at 
the same time becoming thinner and thinner, until at length they are formed 
only of a thin membrane of areolar and elastic tissue, lined by a layer of 
squamous epithelium, no longer provided with cilia. At the same time they 
are altered in shape; each of the minute terminal branches widening out 
funnel-wise, and its walls being pouched out irregularly into small saccular 
dilatations, called air-cells, figure 223, b. Such a funnel-shaped terminal 
branch of the bronchial tube, with its group of pouches or air-cells, has been 
called an infundibulum, figures 223 and 224, and the irregular oblong space 
in its center, with which the air-cells communicate, an intercellular passage. 

FIG. 223. FIG. 224. 

FIG. 223. Terminal Branch of a Bronchial Tube, with its Infundibula and Air-cells, 
from the Margin of the Lung Injected with Quicksilver; Monkey, a, Terminal bronchial 
twig; 6, 6, infundibula and air-cells. X 10. (F. E. Schulze.) 

FIG. 224. Two Small Infundibula, a, a, with air-cells, b, b, and the ultimate bronchial 
tubes, c, c, with which the air-cells communicate. From a new-born child. (Kolliker.) 

An inflated and dried turtle's lung illustrates the homologue of a lobule. 
Such a preparation can be cut across to illustrate the intercellular passage, 
the infundibulum, and the air-cells. 

The air-cells, or air-vessels, are sometimes placed singly, like recesses 
from the intercellular passage, but more often they are arranged in groups 
or even rows, like minute sacculated tubes, so that a short series of vesicles 
all communicating with one another open by a common orifice into the tube. 
The vesicles are of various forms according to the mutual pressure to which 
they are subject. Their walls are nearly in contact, and they vary from o . 3 
to 0.5 mm. in diameter. Their walls are formed of fine membrane similar 
to that of the intercellular passages and continuous with it. The membrane 
is folded on itself so as to form a sharp-edged border at each circular orifice 



of communication between contiguous air-vesicles, or between the vesicles 
and the bronchial passages. Numerous fibers of elastic tissue are spread 
out in the walls between contiguous air-cells, and many of these are attached 
to the outer surface of the wall of which each cell is composed, imparting to 
it additional strength and the power of recoil after distention. 

The air-cells are lined by a layer of epithelium, figure 225, the cells of 
which are very thin and plate-like. The thin epithelial membrane is free on 
one side, where it comes in contact with the air of the lungs, but on the other 

FIG. 225. From a Section of the Lung of a Cat, Stained with Silver Nitrate. A. D, 
Alveolar duct or intercellular passage; S, alveolar septa, N, alveoli or air-cells, lined with 
large, flat, nucleated cells, with some smaller polyhedral nucleated cells; M, unstriped 
muscular fibers. Circular muscular fibers are seen surrounding the interior of the alveolar 
duct, and at one part is seen a group of small polyhedral cells continued from the bronchus. 
(Klein and Noble Smith.) 

side a network of pulmonary capillaries is spread out so densely, figure 226 
that the interspaces or meshes are even narrower than the vessels. These 
are on an average 3^Vo f an inch, or 8 micromillimeters, in diameter. Be- 
tween the atmospheric air-cells and the blood in these vessels, nothing in- 
tervenes but the thin walls of the cells and capillaries. The exposure of the 
blood to the air is the more complete because the wall between contiguous 
air-cells, and often the spaces between the walls of the same, contain only 
a single layer of capillaries both sides of which are at once exposed to the air. 

The air-vesicles situated nearest to the center of the lung are smaller 
and their networks of capillaries are closer than those nearer to the circum- 


ference. The vesicles of adjacent lobules do not communicate. Those of 
the same lobule or proceeding from the same intercellular passage com- 
municate, as a general rule, only near angles of bifurcation, so that when any 
bronchial tube is closed or obstructed the supply of air is lost for all the blood 
vessels of that lobule and its branches. 

Blood Supply. The lungs receive blood from two sources: a, the 
pulmonary artery; b, the bronchial arteries. The former conveys venous 
blood to the lungs for its oxidation, and this blood takes no share in the 

FIG. 226. Section of Injected Lung, Including Several Contiguous Alveoli. (F. E. 
Schulze.) Highly magnified, a, a, Free edges of alveoli; c, c, partitions between neighbor- 
ing alveoli, seen in section; &, small arterial branch giving off capillaries to the alveoli. 
The looping of the vessels to either side of the partitions is well exhibited. Between the 
capillaries is seen the homogeneous alveolar wall with nuclei of connective-tissue corpuscles 
and elastic fibers. 

nutrition of the deeper pulmonary tissues through which it passes. The 
branches of the bronchial arteries are nutrient arteries which ramify in the 
walls of the bronchi, in the walls of the larger pulmonary vessels, and in the 
interlobular connective tissue, etc. The blood of the bronchial vessels is re- 
turned chiefly through the bronchial, but partly through the pulmonary, veins. 
Lymphatics. The lymphatics are arranged in three sets: i. Ir- 
regular lacunae in the walls of the alveoli or air-cells. The lymphatic vessels 
which lead from these accompany the pulmonary vessels toward the root 
of the lung. 2, Irregular anastomosing spaces in the walls of the bronchi. 
3, Lymph spaces in the pulmonary pleura. The lymphatic vessels from all 


these irregular sinuses pass in toward the root of the lung to reach the bron- 
chial glands. 

Nerves. The nerves of the lung are to be traced from the anterior 
and posterior pulmonary plexuses, which are formed by branches of the 
vagus and sympathetic. The nerves follow the course of the blood vessels 
and bronchi, and many small ganglia are situated in the walls of the latter. 

FIG. 227. Capillary Network of the Pulmonary Blood Vessels in the Human Lung. X 60. 



Respiratory movement consists of the alternate expansion and contrac- 
tion of the thorax, by means of which air is drawn into, or expelled from, 
the lungs. 

A movement of the side walls or floor of the chest to increase its diameter 
or length will enlarge the capacity of the interior. By such an increase of 
capacity there will be of course a diminution of the pressure of the air in the 
lungs, and a fresh quantity of air will enter through the larynx and trachea 
to equalize the pressure on the inside and outside of the chest. This move- 
ment is called inspiration. 

The movement which diminishes the capacity of the chest and increases 
the pressure in the interior expels air until the pressure within and that with- 
out the chest are again equal. This movement is called expiration. In both 
cases the air passes through the trachea and larynx, whether in entering or 
leaving the lungs, there being no other communication with the exterior of 
the body. And the lung, for the same reason, remains closely in contact 
with the walls and floor of the chest under all the circumstances described. 
To speak of expansion of the chest is to speak also of expansion of the lung, 
and vice versa. 



Inspiration. The enlargement of the chest during inspiration is due to 
muscular action, which brings about an increase in the size of the chest cavity 
through the contraction of the inspiratory muscles, the role played by the 
lungs being a passive one. The chest cavity is increased in its three axes, 
the vertical, lateral, and antero-posterior diameters. The muscles engaged 
in ordinary inspiration are: the diaphragma, the intercostales externi, and 
the scaleni and levatores costarum. During forced inspiration every 
muscle is brought into play which by its contraction tends to elevate the ribs 

and sternum or which will fix points against 
which these muscles can act. This includes 
almost every muscle of the trunk and neck. 
Changes in the vertical diameter are due, 
first, to the contraction of the diaphragm. 
This muscle has the shape of a flattened 
dome, its highest point being the central 
tendon. While passive its lower portions 
are in apposition with the chest walls, figure 
228, 7. On contraction, the dome is pulled 
downward and the lower portion is pulled 
away from the chest walls, the downward 
displacement varying from 6 to 12 mm. in 
normal respiration, and in forced respira- 
tion may amount to as much as 45 mm. 
The tendency of the diaphragm to pull the 
lower ribs and lower part of the sternum 

inward is counteracted by the outward pressure of the abdominal viscera, 
and by the action of the quadrati lumbori, which by their attachment to 
the last ribs fix these and, in case of deep inspiration, may even pull them 
downward. The serrati postici inferiores also aid, being attached to the 
four lower ribs. 

Changes in the lateral and antero-posterior diameters are effected by the 
raising of the ribs, which are attached very obliquely to the spine and sternum. 
The elevation of the ribs takes place both in front and at the sides the 
hinder ends being prevented from performing any upward movement by 
their pivot attachment to the spine. The movement of the front extremities 
of the ribs is of necessity limited by an upward and forward movement of the 
sternum to which they are attached, the movement being greater at the lower 
end than at the upper end of the sternum. 

The axes of rotation in these movements are two: one corresponding 
with a line drawn through the two articulations which the rib forms with 
the spine, o, b, figure 230, and the other with a line drawn from one of these 
(head of rib) to the sternum, A B, figure 230; the motion of the rib around 
the latter axis being somewhat after the fashion of raising the handle of a 

FIG. 228. Schematic Repre- 
sentation of Diaphragm. In ex- 
piration (7), quiet inspiration 
(77), and deep inspiration (///). 
(After Schaffer.) 



bucket. The elevation of the ribs is accompanied by a slight opening out of 
the angle which the bony part forms with its cartilage, and thus an additional 
means is provided for increasing the antero-posterior diameter of the chest. 
The movements of all the ribs except the twelfth consist of a rotation up- 

L*fl subcUvten artery 
Left common carotid artery 

Left superior intercostal vein 
Left innominate vei 

(cut edge) 



FIG. 229. Thorax from the Left, Showing Left Pleural Sac, and the Diaphragm. The 
lung is removed. (Cunningham.) 

ward, forward, and outward. The twelfth presents only rotation down- 
ward and backward. 

The muscles involved in these movements of the ribs are the external 
intercostals and the part of the internal intercostals situated between the 
costal cartilages. Their action is to widen the intercostal spaces. The 
scaleni fix the first and second ribs, thereby making a fixed point of action 


for the other muscles involved. The serrati postici superiores assist the above 
and also raise the third, fourth, and fifth ribs. The levatores costarum longi 
and brevi elevate and evert all the ribs from the first to the tenth. 

In extraordinary or forced inspiration, which may be due either to violent 
exercise or to interference with the due entrance of air into the lungs, all the 
above muscles act more strongly. The diaphragm descends lower, the 
scaleni raise the first and second ribs instead of merely fixing them, as in 
ordinary respiration, as do also the sterno-cleido-mastoids. These, together 
with the sacro-spinales which straighten the spine, increase the vertical 
diameter. The trapezii and the rhomboidii assist in increasing the antero- 

FiG. 230. Diagram of Axes of Movement of Ribs. 

posterior and lateral diameters by fixing the shoulders and thus giving a 
fixed point for the action of the pectorales and latissimi dorsi. 

The enlargement of the chest during inspiration presents peculiarities 
in different persons. In children of both sexes the principal muscle in- 
volved seems to be the diaphragm, and this type of breathing is known as 
abdominal breathing. In men, the chest and sternum, together with the 
front wall of the abdomen, are subject to a wide movement; this type of 
breathing is called the inferior costal. In women, the movement appears 
less extensive in the lower and more extensive in the upper part of the chest, 
which is called the superior costal type. This has been shown to be due 
rather to mode of dress than to a real difference in the sexes (Mosher). 

Expiration. Quiet expiration is a passive act due to the return of 
the thorax and its contained lungs to their normal position when the mus- 
cles involved in inspiration relax. This elastic recoil is sufficient in ordinary 
quiet breathing to expel air from the lungs. In forced expiration, however, 


which may occur to a slight degree in speaking, singing, etc., as well as in 
the case of many involuntary and reflex acts, such as coughing, sneezing, 
etc., other muscles are involved. Of these the principal are the abdominal 
muscles, obliquus externus and internus, rectus abdominis, transversus ab- 
dominis and pyramidalis . These act, first, by pressing the abdominal 
viscera against the diaphragm and thereby forcing it up, their descent into 
the pelvic cavity being prevented; second, by their attachments to the lower 
ribs and cartilages, the muscles draw these downward and inward, thereby 
lessening the size of the thoracic cavity; lastly, by their contraction, they 
form a fixed point for the action of that part of the internal intercostals, 
not involved in inspiration, to approximate the ribs. 

When by the efforts of the expiratory muscles the chest has been squeezed 
to less than its average diameters, it again, on relaxation of the muscles, 
returns to the normal dimensions by virtue of its elasticity. The construc- 
tion of the chest walls, therefore, admirably adapts them for recoiling against 
and resisting as well undue contraction as undue dilatation. 

Respiratory Movements of the Nostrils and of the Glottis. During 
the action of the inspiratory muscles which directly draw air into the chest, 
those which guard the opening through which the air enters are also active. 
In hurried breathing the dilatation of the nostrils is well seen, although 
under ordinary conditions it may not be noticeable. The opening at the 
upper part of the larynx, however, the rima glottidis, is dilated at each in- 
spiration for the more ready passage of air, and becomes smaller at each 
expiration; its condition, therefore, corresponds during respiration with 
that of the walls of the chest. There is a further likeness between the two 
acts in that, under ordinary circumstances, the dilatation of the rima glot- 
tidis is a muscular act and its contraction chiefly an elastic recoil; although, 
under various special conditions to be hereafter mentioned, there may be 
considerable muscular contraction exercised. 

Methods of Recording Respiratory Movements. The movements of respira- 
tion may be recorded graphically in several ways. The ordinary method is to 
introduce a tube into the trachea of an animal, and to connect this tube by 
some gutta-percha tubing with a T-piece, the side branch of which is connected 
with a Marey's tambour, which may be made to write on a recording surface, 
figure 156. If the tube attached to the free limb of the T-piece be partially 
closed with a screw compress, the movements of inspiration and expiration are 
larger than if it were open. The alteration of the pressure within the lungs on 
inspiration and expiration is shown by the movement of the column of air in 
the trachea and in its extension to the T-piece. By these means a record of the 
respiratory movements may be obtained in experimental animals. 

Various instruments have been devised for recording the movements of 
the chest by application of apparatus to the exterior. Such is the stethometer 
of Burdon-Sanderson, figure 233. This consists of a frame formed of two 
parallel steel bars joined by a third at one end. At the free end of the bars 
is attached a leather strap, by means of which the apparatus may be suspended 



from the neck. Attached to the inner end of one bar is a tambour and ivory 
button, to the end of the other an ivory button. The apparatus is suspended 
with the transverse bar. posteriorly, the button of the tambour is placed on the 
part of the chest the movement of which it is desired to record, and the other but- 
ton is made to press upon the corresponding side of the chest, so that the chest 

FIG. 231. Stethograph or Pneumograph. h, Tambour fixed at right angles to plate 
of steel, /; c and d, arms by which instrument is attached to chest by belt, e. When the 
chest expands, the arms are pulled asunder, which bends the steel plate, and the tambour is 
affected by the pressure of b, which is attached to it on the one hand, and to the upright in 
connection with horizontal screw, g. (Modified from Marey's instrument.) 

is held as between a pair of calipers. The receiving tambour is connected 
through a T-piece with a recording tambour of Marey's and with a bulb by 
means of which air can be squeezed into the cavity of the typanum. When 
adjusted the tube connected with the air ball is shut off by means of a screw 
clamp. The movement of the chest is thus communicated to the recording 

FIG. 232. Tracing of Thoracic Respiratory Movements obtained by means of 
Marey's Pneumograph. A whole respiratory phase is comprised between a and a; 
inspiration during which the lever descends, extending from a to b, and expiration from b 
to a. The undulations at c are caused by the heart's beat. (Foster.) 

A simpler form of this apparatus, called a pneumograph or stethograph, 
consists of a thick india-rubber bag of elliptical shape about three inches long, 
to one end of which a rigid gutta-percha tube is attached. This bag may be 
fixed at any required place on the chest by means of a strap and buckle. By 
means of the gutta-percha tube the variations of the pressure of air in the bag, 



produced by the movements of the chest, are communicated to a recording 
tambour. This principle is applied in a modified form in Marey's pneumo- 
graph, figure 231. 

The variations of intrapleural pressure may be recorded by introducing a 
cannula into the pleural or pericardial cavity. The cannula should be pre- 
viously connected with a mercury or other form of manometer by tubing 
filled with physiological saline. 

Ivory button. 

Tube to commu- 
nicate with re- 
cording tam- 

Ball to fill appa- _. 
ratua with air. 

FIG. 233. Stethometer. (Burdon-Sanderson.) 

Finally, it has been found possible in various ways to record the diaphrag- 
matic movements. This can be done by inserting a receiving tambour into 
the abdomen below the diaphragm, by the insertion of needles into different 
parts of the diaphragm and recording the movement of the free ends of needles 
about the fulcrum formed where the chest wall is pierced, or by recording the 
contraction of isolated strips of the diaphragm directly. These records all 
give an accurate picture of the movements of the diaphragm. 

The Relative Time of Inspiration and Expiration and the Respira- 
tory Movement. The acts of inspiration and expiration take up, under 
ordinary circumstances, a nearly equal time. The time of inspiration, 
however, especially in women and children, is a little shorter than that of 
expiration, and there is commonly a very slight pause between the end of 
expiration and the beginning of the next inspiration, see figure 232. The 
ratio of the respiratory rhythm may be thus expressed: 

Inspiration 6 

Expiration 7 to 8 

Pause Very slight 



If the ear be placed in contact with the wall of the chest or be separated 
from it only by a good conductor of sound or a stethoscope, a faint respiratory 
murmur is heard during inspiration. This sound varies somewhat in dif- 
ferent parts, being loudest or coarsest in the neighborhood of the trachea and 
large bronchi (tracheal and bronchial breathing), and fading off into a faint 
sighing as the ear is placed at a distance from these (vesicular breathing). 
It is heard best in children. In them a faint murmur is heard in expiration 
also. The cause of the vesicular murmur has received various explanations. 
Most observers hold that the sound is produced in the glottis and larger 

FIG. 234. Tracing of the Normal Diaphragm Respirations of the Rabbit, a, With 
quick movement of drum; b, with slow movement; /, inspiration; E, expiration. To be 
read from left to right. (Marckwald.) 

bronchial tubes, but that it is modified in its passage to the pulmonary 
alveoli. In disease of the lungs the vesicular murmur undergoes various 
modifications, for a description of which One must consult text-books on 
physical diagnosis. 

The Quantity of Air Breathed. Tidal air is the quantity of air 
which is habitually and almost uniformly changed in each act of breathing. 
In a healthy adult man it is about 30 cubic inches, or about 500 cc. or half 
a liter. In college students the tidal air is somewhat less, varying from 300 
to 400 cc. while at rest. 

The complemental air is the quantity of air which can be drawn into the 
lungs by the deepest inspiration over and above that which is in the lungs 
at the end of an ordinary inspiration. Its amount varies, but may be reck- 
oned as 100 cubic inches, or about 1,600 cc. 



The reserve air is that which may be expelled by a forcible and deeper 
expiration, after an ordinary expiration, such as that which expels the 
tidal air. The reserve air amounts to from 1,200 to 1,500 cc. This is also 
termed the supplemental air. 

FIG. 235. Photograph of the Sanborn Company form of spirometer. The grad- 
uated disc records the volume of air exhaled. In using the spirometer the reservoir is 
first filled with water to form a water seal for the air chamber. To perform a respi- 
ratory volume test the instrument is set automatically at zero, though it is well to 
begin with the air chamber empty. Place the previously sterilized mouth piece between 
the lips and if necessary, close the nostrils with pinch cock or with the hand. The 
receiving chamber is delicately balanced and as the breath is forced through the tube into 
this bell it rises, recording the movement on the circular index, from the scale of which 
the volume is read off directly. For very accurate comparative determinations the 
expired air should be allowed to stand long enough to come to constant temperature, 
and corrections for variations from the standard temperature and pressure should be 
made. This is not necessary in the routine laboratory and gymnasium measurements. 

The residual air is the quantity which still remains in the lungs after 
the most violent expiratory effort. Its amount depends in great measure 
on the absolute size of the chest, but may be estimated at about i ,000 cc. 

tO 1,200 CC. 

The quantity of air breathed per minute, called the minute volume, 
varies in the adult at rest according to size. But the average may be set 
down as between 5 and 8 liters. In 24 hours this would amount to from 


7,200 to 11,500 liters. However, many factors lead to great variations in 
this volume. Vigorous exercise will increase the minute volume to 12 to 
15 or more liters per minute. Breathing a rarefied air will produce the 
same result, as in mountain climbing or aviation. The lack of oxygen or 
anoxemia augments the minute volume both by accelerating the respira- 
tory rate and increasing the depth. Excess of carbon dioxide, or 
after moderate carbon monoxide poisoning, similar response is given, 
though the rate is more vigorously affected on breathing air rich in carbon 

The Respiratory Capacity. The greatest respiratory capacity or vital 
capacity of the chest is indicated by the quantity of air which a person can 
expel from his lungs by a forcible expiration after the deepest possible in- 
spiration. The vital capacity is the sum of the reserve, tidal, and comple- 
mental airs. It expresses the power which a person has of breathing in the 
emergencies of active exercise, violence, and disease. The average 
capacity of an adult, at 15.4 C. (60 F.), is about 225 to 250 cc., or 
3,500 to 4,000 cc. In healthy men, the respiratory capacity varies chiefly 
with the stature, weight, and age. 

Circumstances Affecting the Amount of Respiratory Capacity. John 
Hutchinson states that for every centimeter of height above the standard 
the respiratory capacity is increased, on an average, by 50 cc. 

The influence of weight on the capacity of respiration is less manifest, 
and considerably less than that of height. It is difficult to arrive at any 
definite conclusions on this point, because the natural average weight of a 
healthy man in relation to stature has not yet been determined. 

The capacity appears to be increased by age from about the fifteenth 
to the thirty-fifth year, at the rate of 80 cc. per year; from thirty- 
five to sixty-five it diminishes at the rate of about 25 cc. per year; so 
that the capacity of respiration of a man sixty years old would be about 
480 cc. less than that of a man forty years old, of the same height and 

The number of respirations in a healthy adult person usually ranges 
from 14 to 1 8 per minute. It is greater in infancy and childhood. It 
varies also much according to different circumstances, such as exercise or 
rest, health or disease, etc. Variations in the number of respirations corre- 
spond ordinarily with similar variations in the pulsations of the heart. In 
health the proportion is about i to 4, or i to 5 ; and when the rapidity of 
the heart's action is increased, that of the chest movement is commonly 
increased also, but not in every case in equal proportion. It happens 
occasionally in disease, especially of the lungs or air-passages, that 
the number of respiratory acts increases in quicker proportion than the 
beats of the pulse; and, in other affections, much more commonly, 


that the number of the pulses is greater in proportion than that of the 

The Force of Inspiratory and Expiratory Muscles. The force which 
the inspiratory muscles are capable of exerting on the chest is greatest 
in muscular individuals of the mean height of about five feet seven or 
eight inches and is equal to a column of two and a half to three inches of 
mercury. The force manifested in the strongest expiratory acts is, on the 
average, one-third greater than that exercised in inspiration. But this 
difference is in a great measure due to the power exerted by the elastic 
reaction of the walls of the chest; and it is also much influenced by the 
disproportionate strength which the expiratory muscles attain from their 
being called into use for other purposes than that of simple expiration. 

Within the limits of ordinary tranquil respiration the elastic resilience 
of the walls of the chest favors inspiration. It is only in deep inspiration 
that the ribs and rib cartilages offer an opposing force to dilatation. In 
other words, the elastic resilience of the lungs, at the end of an act of 
ordinary exhalation has drawn the chest walls within the limits of their 
normal degree of expansion. Under all circumstances, of course, the 
elastic tissue of the lungs opposes inspiration and favors expiration. 

It is possible that the contractile power which the bronchial tubes and 
air- vesicles possess, by means of their muscular fibers may assist in expiration. 
But it is more likely that its chief purpose is to regulate and adapt, in some 
measure, the quantity of air admitted to the lungs, and to each part of them, 
according to the supply of blood. The muscular tissue contracts upon and 
gradually expels collections of mucus, which may have accumulated within 
the tubes, and which cannot be ejected by forced expiratory efforts, owing 
to collapse or other morbid condition of the portion of lung connected with 
the obstructed tubes (Gardner). Apart from any of the before- mentioned 
functions, the presence of muscular fiber in the walls of a hollow viscus, such 
as a lung, is only what might be expected from analogy with other organs. 
Subject as the lungs are to such great variation in size, it might be antici- 
pated that the elastic tissue, which enters so largely into their composition, 
would be supplemented by the presence of much muscular fiber. 


Composition of the Atmosphere. The atmosphere we breathe has, 
in every situation in which it has been examined in its natural state, a nearly 
uniform composition. It is a mixture of oxygen, nitrogen, carbon dioxide, 
and watery vapor, with, commonly, traces of other gases, as argon, ammo- 
nia, sulphureted hydrogen, etc. Of every 100 volumes of pure atmospheric 
air, 79 volumes, on an average, consist of nitrogen and argon, the remaining 


21 of oxygen. The proportion of carbon dioxide is extremely small; 10,000 
volumes of atmospheric air contain only about 4 of that gas. 

The quantity of watery vapor varies greatly according to the tempera- 
ture and other circumstances, but the atmosphere is never without some. 
In this country the average quantity of watery vapor in the atmosphere 
varies greatly according to the region. In some of our Western arid plains 
in the dry season the air is almost free of moisture. 

Character and Composition of Air which has been Breathed. 
The changes effected by respiration in the atmospheric air are: i, an increase 
of temperature; 2, a diminution in the quantity of oxygen; 3, an increase in 
the quantity of carbon dioxide; 4, a diminution of volume; 5, an increase in 
the amount of watery vapor; 6, the addition of a minute amount of organic 
matter and of free ammonia. 

Temperature of the Expired Air. Expired air, after its contact with the 
Interior of the lungs, is hotter (at least in most climates) than the inspired air. 
its temperature varies between 36 and 37.5 C. (97 and 99.5 F.), the 
lower temperature being observed when the air has remained but a short 
time in the lungs. Whatever may be the temperature of the air when in- 
haled, it acquires nearly that of the blood before it is expelled from the chest. 

The Oxygen of Expired Air. Pettenkofer and Voit have found that the 
mean consumption of oxygen during 24 hours by a man weighing 70 kilos 
is about 700 grams or 490 liters. The quantity of oxygen absorbed increases 
with muscular exercise, and falls during rest. In general terms the quantity 
absorbed varies with the activity of the metabolic processes, following very 
closely the variation of carbon dioxide under the conditions outlined below. 

The Carbon Dioxide of Expired Air. The percentage of carbon dioxide 
is increased in expired air, but the total quantity of carbon dioxide exhaled 
in a given time is subject to change from various circumstances. From 
every volume of air inspired 4 to 5 per cent, of oxygen is abstracted; while 
a rather smaller quantity, 4.38 per cent., of carbon dioxide is added in its 
place. The expired air will contain, therefore, 438 volumes of carbon di- 
oxide in 10,000. The total quantity of carbon dioxide exhaled into the air 
breathed by a healthy adult, calculating that 15.4 cc. of the 350 cc. of the 
average air exhaled at each expiration consists of carbon dioxide, and that 
the rate of respiration per minute is on an average 16, would be about 400 
liters in twenty-four hours. From actual experiment this amount seems 
to be a trifle too great, since from the average of many investigations the 
total amount of carbon dioxide excreted per day by the entire body has been 
found to be about 400 liters, weighing 800 grams, and consisting of 218 
grams of carbon, and 582 grams of oxygen. From the 218 grams of carbon 
must be deducted about 10 grams excreted in other ways than by the lungs, 
which leaves about 215 grams as the amount of carbon excreted by the aver- 
age healthy man by respiration each day and night. These quantities 



must be considered approximate only, inasmuch as various circumstances, 
even in health, influence the amount of carbon dioxide excreted, and, cor- 
relatively, the amount of oxygen absorbed. 

The total amount of carbon dioxide excreted is influenced sharply by a 
number of factors: First, the depth and volume of respiratory movements. The 
greater the volume of air breathed, the greater the total output of carbon 
dioxide, though the percentage per unit of 
expired air is decreased. This influence de- 
pends upon the more efficient oxidative 
processes in the presence of more thorough 
ventilation of the lungs and blood. Second, 
the carbon dioxide output varies with age. 
It is greater with children and youth than 
with the old. In extreme old age the total 
output may not exceed that of the ten-year- 
old child. Third, there is a diurnal variation 
in carbon dioxide output. The respiratory 
quotient, i.e., the ratio between carbon 
dioxide eliminated and oxygen absorbed, is 
greater during the day than during the 
night. In the day, therefore, the carbon 
dioxide exhaled in relation to the oxygen 
absorbed is increased, and it is diminished 
during the night. This is probably due to 
the increased production of carbon dioxide 
as a result of increased tissue activity during 
the day, and, consequently, the breaking 
down or katabolism of more substances. 
Fourth, the character and quantity of the 
food greatly influence the proportion of 
carbon dioxide as indicated by the respira- 
tory quotient. It is greater with carbohy- 
drate foods. During fasting there is for the 
first two or three days an increased carbon 
dioxide output, but later this is decreased. 
Fifth, the bodily exercise, in moderation, 
increases the quantity of carbon dioxide ex- 
pired by at least one-third more than it is 

during rest. For about an hour after exercise the volume of the air expired 
in the minute is increased nearly 2,000 cc., or 118 cubic inches; and the 
quantity of carbon dioxide about 125 cc., or 7.8 cubic inches per minute. 
Violent exercise, such as full labor or athletic competition, still further in- 
creases the amount of the carbon dioxide exhaled. Sixth, the observations 
made by Vierordt at various temperatures between 3.4-23.8 C. (38 F. 
and 75 F.) show, for warm-blooded animals, that within this range every 
rise equal to 5.5 C. (10 F.) causes a diminution of about 33 cc. (2 cubic 
inches) in the quantity of carbon dioxide exhaled per minute. 

The Volume of the Respired Air is Diminished. When allowance has 
been made for the expansion in heating, the volume of expired air is decreased, 

FIG. 236. Apparatus for Esti- 
:> 2 and CO 2 in Expired 


the loss being due to the fact that a portion of the oxygen absorbed is not 
returned in the form of carbon dioxide. Since the oxygen of a given volume 
of carbon dioxide would have the same volume as the carbon dioxide itself 
at a given temperature and pressure, a portion of the oxygen absorbed 
must be used for other purposes than the formation of carbon dioxide. 
In fact, some of it is used in the formation of urea, some in the formation 
of water, etc. The volume of the carbon dioxide exhaled, divided by the 
volume of the oxygen absorbed, gives what is known as the respiratory quo- 
tient; thus 

CO 2 exhaled 

O 2 absorbed 

Normally in man on a mixed diet the respiratory quotient averages 0.82 

4.0 to 4.5 

= o. 8 to 0.9. 

But it is subject to variation through several causes; for example, through 
variation in the composition of the diet. On a pure carbohydrate diet the 
respiratory quotient will rise above 0.9, i.e., to i.o, since carbohydrates 
contain enough oxygen to oxidize the hydrogen in the molecule. On a diet 
containing much fat the quotient is lowest, since relatively more oxygen is 
needed completely to oxidize fat. The theoretical respiratory quotient for 
fats is 0.7. The same is true, but to a less degree, in the case of proteins 
which also require much oxygen for their complete oxidation. Muscular 
exertion raises the respiratory quotient, because in its performance carbo- 
hydrates are used up in relatively greater quantity. 

The Watery Vapor in Respired Air. The quantity of water vapor emitted 
is, as a general rule, sufficient to saturate the expired air, or very nearly so. 
Its absolute amount is, therefore, influenced by the following circumstances: 
i. By the quantity of air respired; for the greater the volume of air, the 
greater also will be the quantity of moisture exhaled; 2. by the quantity of 
water vapor contained in the air previous to its being inspired; because the 
greater the moisture inhaled, the less will be the amount to complete the 
saturation of the air; 3. by the temperature of the expired air; for the higher 
the temperature the greater will be the quantity of water vapor required to 
saturate the air; 4. by the length of time which each volume of inspired air 
is allowed to remain in the lungs; for although, during ordinary respiration, 
the expired air is always saturated with water vapor, yet, when respiration is 
performed very rapidly, the air has scarcely time to be raised to the highest 
temperature or be fully charged with moisture ere it is expelled. 

The quantity of water exhaled from the lungs in 24 hours ranges (accord- 
ing to the various modifying circumstances already mentioned) from about 
200 to 800 cc., the ordinary quantity being about 400 to 500 cc. Some of 
this is probably formed by the chemical combination of oxygen with hydro- 


gen in the system; but the far larger proportion of it is water which has been 
absorbed, as such, into the blood from the alimentary canal, and which is 
exhaled from the surface of the air-passages and cells, as it is from the free 
surfaces of all moist animal membranes, particularly at the high tempera- 
ture of warm-blooded animals. 

A small quantity of ammonia is added to the ordinary constituents of 
expired air. It seems probable, however, both from the fact that this sub- 
stance cannot be always detected and from its minute amount when present, 
that the whole of it may be derived from decomposing particles of food left 
in the mouth or the teeth, and that it is, therefore, only an accidental con- 
stituent of expired air. 

The Organic Matter in Expired Air. It was formerly supposed that this 
organic matter was injurious and gave rise to the unpleasant symptoms 
which are experienced in badly ventilated rooms. But this has been strongly 
questioned so that the matter cannot be considered settled at the present 


Pressure and Diffusion of the Air. It must be remembered that 
the tidal air in the lungs amounts only to from 300 to 500 cc. at each in- 
spiration. This amount at once mixes with the reserve and the residual 
air already in the lungs. The mixture is facilitated by the air currents set 
up in the deeper parts of the lungs by the sudden entrance of the tidal air; 
but, after all is considered, it will be found that diffusion is the greatest factor 
in producing a uniform mixture of the gases in the alveoli and in the air-cells 
of the lungs. Just as a fresh supply of oxygen introduced within the door 
of a closed room will quickly diffuse throughout the space of the entire room 
so will the fresh tidal air diffuse into the space of the lungs. When the 
tidal air is expired its average composition has been changed so it has only 
about 16 per cent, of oxygen instead of the usual 20. 96 per cent, of oxygen in 
air. The oxygen content of the air still left in the lungs is probably some- 
what less than the percentage in this expired air for the reason that, the air 
of the respiratory tree, the trachea, bronchi, and bronchioles, is never fully 
mixed with the alveolar air. 

The partial pressure of the oxygen of the air measured under standard 
conditions is 159 mm. of mercury; that is, 20. 96 per cent, of 760 mm. of mer- 
cury, the standard pressure of one atmosphere. The partial oxygen pressure 
in expired air with 16 per cent, of oxygen is only 122 mm. of mercury. These 
figures show a diffusion pressure of at least 37 mm. of mercury to carry 
oxygen into the deeper recesses of the lungs. The constant loss of oxygen 
to the blood probably keeps the mean difference greater. 

The Gases of the Blood. Turning now to the consideration of the 
gases of the blood in the lungs, a somewhat different picture presents itself. 

3 02 


The blood consists of a fluid plasma with a mass of corpuscles floating in 
it. The gas analysis of the blood shows that it contains oxygen, carbon 
dioxide, nitrogen, and traces of other inert gases. The blood gases are 
measured by the method of extracting them, measuring the volume and 
computing the volume to standard temperature and pressure. 

Numerous analyses of the blood from the arteries and veins of normal 
men have recently been obtained by Stadie, Harrop, and others, made 
possible by the development of the micro-analytical methods and appara- 
tus introduced by Van Slyke, Fig. 237. Arterial blood obtained by 
puncture from the radial artery with a slender hypodermic needle and 
syringe have yielded on analysis the following average volumes per cent, 
of oxygen. 

Arterial and Venous Oxygen, Total Oxygen Capacity, and Arterial and Venous Oxygen Unsaturation 
in Five normal Individuals (Stadie) 

Oxygen content 


Individual number 






per 100 cc. 

per 100 cc. 

per 100 cc. 

of blood 

of blood 

of blood 

Per 100 cc. 


Per 100 cc. 


of blood 


of blood 






I .2 





21 .0 










23 3 

I . 2 




















2O. 2 


21 . 2 

I .0 




The amount of oxygen per unit quantity of blood varies with the con- 
centration of hemoglobin. In blood from the radial artery the sample is 
under normal respiratory conditions about 93 to 97 per cent saturated, 
See Harrop, Table I. 

The amount of carbon dioxide in the total blood averages about 40 
volumes per cent, in arterial blood and 46 to 58 volumes per cent, in venous 
blood. Venous blood may contain as much as 65 volumes per cent, of car- 
bon dioxide. The carbon dioxide-carrying bases are largely in the plasma 
and increase or decrease with variations of acid or alkali production, 
thereby maintaining equilibrium. The amount of nitrogen in solution in 
the blood follows closely its ratio of physical absorption by fluids. Saturated 
arterial blood contains 1.52 volumes per cent, of nitrogen. Venous blood 
contains somewhat less, about 1.36 volumes per cent. (Van Slyke and 




For extracting the gases from the blood the older methods using the mercurial air 
pumps of Ludwig, Geissler, or Sprengel have given place to much simpler and more 
convenient microapparatus of Van Slyke, Fig. 237. The Van Slyke apparatus can be 
used for the analysis of oxygen, or of carbon dioxide, and of the inert residue of nitrogen 
by difference. 

The Van Slyke Blood Gas Apparatus. -The Van Slyke apparatus consists of a 50 cc. 
pipette with three-way stop cocks, e and /, at the top and bottom. The top of the pip- 
ette is graduated in i cc. and .02 cc. divisions. A . 
reservoir of 80 cc. capacity is connected with the 
bottom of the apparatus by a heavy black rubber 
tubing of small bore and the whole apparatus filled 
with mercury. The sample of blood to be analyzed 
is introduced through the cup b into the pipette and 
the gases evacuated and measured according to the 
following technique. 

The solutions required are ammonia solution to 
which is added the soluble saponine from 5 grams of 
commercial soap bark and 4 cc. concentrated am- 
monia per liter; redistilled caprillic alcohol to prevent & \mabort 
foaming; and 10 per cent, potassium ferricyanide 

Volume of Gas Measured. 

Column of Water Solution 

Level of Mercury Surface 
in Levelling Bulb. 
vLevel of Mercury 
Menijcuj m Pipette. 

FIG. 2370. 

FIG. 237. 

in normal potassium hydrate. A determination is made by the following steps. Intro- 
duce 3 drops of caprillic alcohol and 6 cc. ammonia into the pipette, evacuate and wash 
out the dissolved air, run 2 cc. of air-free ammonia back up in the cup as a seal. A 2 cc. 
sample of fresh arterial blood drawn under oil is run from a 2 cc. graduated pipette into 
the cup under the ammonia solution and drawn down into the pipette. Mix the solu- 
tions until the blood is completely laked, which occurs in a few seconds. Next intro- 
duce 0.4 cc. of 10 per cent, ferricyanide to set the oxygen free from the hemoglobin. 
This dissociation is facilitated by lowering the mercury to about the 50 cc. mark on the 
pipette thus producing a Toricellian vacuum in which the blood and reagent mixture is 


shaken vigorously for about one minute. Make a preliminary reading of the liberated 
gas and repeat the evacuation until the readings check. For final reading draw the 
fluids into the chamberd below the lower stopcock, using care not to trap any gas, and 
run the mercury around the side tube c, level the mercury bulb against the mercury 
meniscus in the graduated limb as in Fig. 2376 and read. The gas of the 2 c.c. sample 
of blood consists of the oxygen bound by the hemoglobin and of the air in solution at the 
temperature and barometer of the analysis. The corrections for dissolved air including 
nitrogen are readily made from tables of solubility. (See Van Slyke in Journal of Bio- 
logical Chemistry, Vol. 33, p. 126; also Vol. 49, p. i.) 

The large quantity of oxygen found in arterial and in venous blood is 
the more striking when the facts of absorption of gases by liquids are 
reviewed. A liquid such as water will, when exposed to a gas, take up the 
gas by absorption according to definite physical laws. Under constant 
temperature the amount of gas absorbed, oxygen for example, varies 
directly as the pressure of the gas, or partial pressure if the gas is in a mix- 
ture. The oxygen absorbed by water from pure air is in direct pro- 
portion to the partial pressure of oxygen in the air, which is 159 mm. 

The amount of gas absorbed by i c.c. of water under standard pressure 
(one atmosphere at o c C.) is termed the absorption coefficient. The 
absorption of oxygen by water for one atmosphere of oxygen is .048 c.c. 
For blood plasma the coefficient is a little less than for water. The 
amount of oxygen in simple solution in 100 c.c. of blood at the partial 
pressure of oxygen in alveolar air is therefore only about 0.32 c.c. The 
actual amount of oxygen in solution in any particular specimen of plasma 
is rather less and is determined by the oxygen tension. 

The saturation of oxygen in arterial whole blood is measured by the 
method of subjecting the blood to an atmosphere in which the oxygen 
tension is accurately known. The instrument is called a tonometer. 
The procedure depends upon the fact that a thin film of blood exposed to 
mixtures of gases in air gives up gases to or absorbs them from the air 
until an equilibrium is established. When a sample of whole blood is 
exposed to atmospheric air in a tonometer the blood becomes fully satur- 
ated with oxygen and the volume it contains is spoken of as the capacity. 
When such blood has its gases extracted by the Van Slyke apparatus and 
the results computed to standard, the volumes per cent, contained are 
such as indicated in the table, page 302. When alveolar airs are used 
the degree of saturation is of course proportionately less than the satu- 
ration against pure air because of the diminished per cent, of alveolar 
oxygen. The volumes per cent, of oxygen absorbed is found to vary also 
according to the per cent, of oxygen in the sample of air and the content 
of hemoglobin in the blood. 

By means of the tonometer observers have measured the tension of 



blood gases. The oxygen tension has been found to be from 4 (S trass- 
burg) to 10 (Herter) per cent, of an atmosphere. Many determinations 
have been given of both lower and higher percentages, but, accepting the 
above limits for a working average, the oxygen tension in arterial blood 
would be from 30.4 to 76 mm. of mercury or more. 

Blood plasma exposed to an air with a partial pressure of 30 to 76 mm. 
of mercury would absorb only from to 0.32 (0.26 c.c. Pfluger) c.c. 
of oxygen for 100 c.c. of blood. As a matter of fact 100 c.c. of whole 



10 20 30 40 50 60 70 80 90 100 

FIG. 238. Dissociation curves of oxyhemoglobin. The figures along the ordinates 
represent percentages of saturation of hemoglobin by oxygen. The figures along the 
abscissae represent mm. of oxygen pressure in mercury. 

I. Bohr's dissociation curve of oxyhemoglobin dissolved in water. 

II. Dissociation curve of oxyhemoglobin dissolved in Ringer's Solution. (After 
Barcroft and Camis.) 

blood has a capacity of an average of from 18.5 c.c. (the Haldane stand- 
ard) to 22.6 c.c. or more of oxygen. It is evident that blood carries far 
more oxygen than can be held in simple solution. The red blood corpus- 
cles carry their enormous excess of oxygen by virtue of the special respira- 
tory pigment, hemoglobin. 

3 o6 


Combining Power of Hemoglobin with Oxygen. One hundred 
cubic centimeters of blood contain about 14 grams of hemoglobin, page 
137. Each gram of hemoglobin, when fully saturated with oxygen, accord- 
ing to Hiifner's earlier determination, combines with 1.56 cc. of oxygen. 
By later work he gets the determination of 1.34 cc. for hemoglobin of ox 
blood. This last figure indicates that the combining power of the hemo- 
globin is dependent upon the iron in the molecule, in which one atom of iron 
combines with one atom of oxygen. A number of investigators have 



















FIG. 239. Dissociation curves of oxy hemoglobin in: I, 0.7 per cent, sodium chlor- 
ide; II, in sodium bicarbonate, and III, in disodium phosphate. The figures along the 
ordinates represent percentages of saturation of hemoglobin by oxygen. The figures 
along the abscissae represent mm. of oxygen pressure in mercury. (Barcroft and Camis.) 

examined the conditions under which hemoglobin combines with oxygen 
Hiifner, Bohr, Lowy, and Barcroft and Camis. Hiifner, working with 
purified hemoglobin in watery solution, found that when the oxygen ten- 
sion in the air in contact with the hemoglobin was increased above zero by 
graded stages, the amount of oxygen that was combined was very great per 
unit of increased pressure at the low pressures, but relatively less at the 



higher pressures. Or, which amounts to the same, if hemoglobin saturated 
with oxygen be subjected to decreasing oxygen pressure, it sets free the 
combined oxygen, at first slowly, then more rapidly. By consulting the 
typical curve showing this relation, it will be evident that the critical 
partial oxygen pressures influencing this combination fall at about 30 to 
35 mm. mercury of oxygen tension and below. See figure 238. 

A number of factors influence the dissociation of oxygen from hemo- 
globin at a given oxygen tension. Of prime importance is the influence of 
the presence of carbon dioxide gas as shown by Bohr and confirmed by 
Barcroft and Camis. With an increase in the tension of carbon dioxide 
there is a decrease in the fixation of oxygen. 


Tensions of oxygen in mm. mercury and the per cent, of saturation 

Tension of car- 

of the hemaglobin at each pressure 

bon dioxide 














5 mm. COz 














10 mm. COz 














20 mm; CO2 




S3- 8 









40 mm. COz 


1 1 








88. 5 



80 mm. COz 













The salts of the blood also influence the oxygen fixation by hemo- 
globin under a given tension as indicated in the following table: 





1. Hemoglobin in water dissociation . : 62 per cent. 

2. Hemoglobin in o . 7 per cent. NaCl dissociation .... 75 per cent. 

3. Hemoglobin in Ringer's solution dissociation 85 per cent. 

4. Hemoglobin in NaHCO 3 solution dissociation 89 per cent. 

5. Hemoglobin in 0.9 per cent. KC1 dissociation 91 per cent. 

6. Hemoglobin in Na 2 HPO 4 solution dissociation. ... 93 per cent. 

Barcroft and Camis find that the dissociation curve also varies in the 
blood of different animals. Strassburg gives the oxygen tension of arterial 
blood as 29.64 mm. of mercury, and for venous blood 22.04 mm. of mer- 
cury. That is to say, during the brief interval in which the blood is in 
the pulmonary capillaries the oxygen tension has increased by 7.6 mm. 
of mercury, an increase of tension which would produce very little increase 
in simple absorption of oxygen. Yet it is sufficient to cause fixation of 
from four to five volumes per cent, of oxygen by the hemoglobin. 

It is evident that there will be diffusion of oxygen from the high tension 


toward the lower and in the direction indicated by the arrows in the table 
below. As fast as the oxygen diffuses into the venous blood, thus tending to 
raise the pressure of the gas in solution, it is taken up and fixed by the hemo- 
globin. This process proceeds far enough during the interval the blood is 
in the pulmonary capillaries to raise the oxygen tension from 22.04 mm. 
of mercury to 29 . 64 mm. of mercury, and also far enough to permit of the 
fixation of from four to five volumes per cent, of oxygen. The oxygen 
diffusion pressures are indicated as follows: 

Oxygen pressure in the atmosphere 2 1 per cent, or 1 59 mm. of mercury 


Oxygen pressure in the alveolar air 16 per cent, or 122 mm. of mercury 


Oxygen pressure in the venous blood 3 per cent, or 22 .04 mm. of mercury 

Liberation of Oxygen in the Tissue Capillaries. When the arterial 
blood reaches the capillaries of the tissues, then the situation which we have 
just found holding good in the lungs is reversed. As rapidly as the oxygen 
reaches the living protoplasm of the tissues it enters into fixed combination, 
thus rendering it inert. The oxygen tension in the tissue cells will, there- 
fore, be zero. Under these conditions the difference in pressure level be- 
tween the oxygen tension in the blood and that in the tissues is sufficient to 
cause a rapid diffusion of oxygen through the capillary walls with correspond- 
ing liberation of the oxygen from the hemoglobin according to the laws of 
combination given in the curves above. The total effect of this process is to 
maintain a relatively high and constant diffusion pressure of the oxygen in 
the blood. During the time the blood remains in the capillaries the total 
oxygen tension will have been lowered from 29 .64 to 22 .04 mm. of mercury, 
yet this slight lowering of tension is sufficient to liberate from four to five 
volumes per cent of oxygen. This figure, of course, is comparative. In 
many of the very active tissues, such as in muscle, a much larger per cent, 
of oxygen will have been dissociated and the oxygen tension correspondingly 
lowered so that the venous blood returning through such an active organ 
may not have more than half the average amount of oxygen found in venous 

Considering the pressure relations of oxygen from the time of its intro- 
duction into the body with the fresh air to its fixation in the tissues we have 
the following schema: 

Oxygen pressure in the atmosphere 1 59 mm. 


Oxygen pressure in the alveolar air 122 mm. 


Oxygen pressure in the venous blood 22 .04 mm. 

Tension of oxygen in the arterial blood 29 . 64 mm. 


Tension of oxygen in the tissues o . oo mm. 


Elimination of Carbon Dioxide by the Blood and the Respiratory 
Apparatus. The principles of absorption of gas by liquids discussed 
in the preceding pages apply equally well for carbon dioxide with the excep- 
tion that carbon dioxide is about three times as soluble in blood as is oxygen. 
The carbon dioxide results from the oxidative processes going on in the tis- 
sues, and this gas is present in large quantities in the tissues and their im- 
mediately surrounding lymph. An analysis of the carbon- dioxide content 
of venous blood reveals the presence of about 45 cc. of the gas in 100 cc. of 
blood. This gas, like oxygen, is held in such large quantity by virtue of the 
fact that it forms loose chemical combinations in the blood. Of the total 
quantity not more than 5 per cent, is held in simple solution. From 10 to 
15 per cent, of the total volume is found in firm combination in such forms 
as carbonates, bicarbonates, etc. The remaining 85 and more volumes 
per cent, is held in loose chemical combination, a combination which is broken 
up under the same conditions of variation in carbon-dioxide tension as 
were found to exist for oxygen in combination with hemoglobin. In the case 
of carbon dioxide an analysis of plasma reveals the fact that the gas is in com- 
bination with some compound of the plasma, probably a protein. In fact, 
there is some evidence to show that carbon dioxide combines with the globu- 
lin group. Carbon dioxide also forms loose chemical compounds with the 
constituents of the red corpuscles, probably with the protein portion of the 
hemoglobin molecule. The pressure relations of this gas as regards its 
diffusion in the process of elimination are shown in the following table: 

Carbon-dioxide tension in the tissues 58 mm. of mercury 


Carbon-dioxide tension in the venous blood 45 mm. of mercury 


Carbon-dioxide tension in the alveolar air . . 23 to 38 mm. of mercury 


Carbon-dioxide tension in the expired air ... 5.8 mm. of mercury 

Theories of Interchange of Gases in the Lungs and in the Tissues. 
The above discussion is on the basis of the mechanical interpretation of the 
transfer of gases in the lungs and in the tissues. By this theory it is assumed 
that the oxygen passes from the air in the lungs through the moist pulmonary 
membrane of the alveoli through the capillary walls and into the blood 
plasma, obeying the physical laws of gas diffusion. Likewise in the tissues 
this theory presupposes that the difference in the mechanical tension in the 
capillary blood plasma, the lymph, and the living tissue will lead to diffusion 
of the oxygen in the direction of lowest pressure, i.e., toward the tissues. 

Some facts have indicated that we cannot account for the transference 
of oxygen by the purely mechanical theory. The idea has been advanced 
that the living epithelial wall of the lung, as well as that of the capillaries, 
exerts a distinct influence on the passage of oxygen of such nature that it 


might be regarded as a secretion of this gas. This theory finds some 
support in that a distinct secretion of oxygen in the air bladders of certain 
fishes has been proven by Bohr. The theory apparently does not apply 
to mammals. 


Respiratory movement is essentially an involuntary act. Unless this 
were the case, life would be in constant danger, and would cease on the 
loss of conciousness for a few moments, as in sleep. It is, however, of ad- 
vantage to the body that co-ordination of respiratory movements should 
be to some extent under the control of the will. For, were it not so, it 
would be impossible to perform those voluntary respiratory acts, such 
as speaking, singing, and the like. 

The Respiratory Nerve Center. It has been known for centuries 
that there exists a region of the central nervous system on the destruction of 
which both respiration and life cease. Flourens, 1842, after many series 
of experiments as to the exact position of what he called the "knot of life" 
(n&ud -vital) , placed it in the floor of the fourth ventricle, at the point of the V 
in the gray matter at the lower end of the calamus scriptorius; a district of 
considerable size, some 5 mm. in extent on each side of the middle line. 
Observers subsequent to Flourens have attempted to show that the chief 
respiratory center, on the one hand, is situated higher up in the nervous 
system, in the floor of the third ventricle (Christiani), or in the corpora quad- 
rigemina (Martin and Booker, Christiani, and Stanier), or lower down in 
the spinal cord. The balance of experimental evidence, however, is to prove 
that the sole centers for respiration are in a limited district in the medulla 
oblongata in close connection with the vagus nucleus on each side. They 
are approximately identical in location. The destruction of this region stops 
respiration. If the center be left in connection with the muscles of respira- 
tion by their nerves, although the remainder of the central nervous system be 
separated from it, respiration continues. It may be considered almost cer- 
tain that the medullary center is the only true respiratory center. Langen- 
dorff states that in newly born animals in which the medulla has been im- 
mediately cut across at a level a few millimeters below the point of the 
calamus scriptorius, respiration continues for some time, but this is ques- 
tionable. Normal respiration does not occur after separation of the bulb 
from the cord, and the so-called respiratory movements noticed by Langen- 
dorff are merely tetanic contractions of the respiratory muscles in which often 
enough other muscles take part. 

The action of the medullary center is to send out impulses during in- 
spiration, which cause contractions of the inspiratory muscles a, of the 
nostrils and jaws, through the facial and inferior division of the fifth nerves; 
b, of the glottis, chiefly through the inferior laryngeal branches of the vagi; c 


of the intercostal and other muscles which produce raising of the ribs, chiefly 
through the intercostal nerves, and d, of the diaphragm, through the phrenic 
nerves. If any one of these sets of nerves be divided, respiratory movements 
of the corresponding muscles cease. Similarly it may be supposed that 
the center sends out impulses to certain other muscles during expiration. 

It has been suggested, however, that the center is double, that it is made 
up of inspiratory cells which are constantly in action, and of an expiratory 
group of cells which act less generally, inasmuch as ordinary tranquil ex- 
piration is seldom more than an elastic recoil, and not a muscular act to 
any marked degree. 

The respiratory center is also bilateral, as has been proven by the method 
of antero-posterior section of the medulla. The tracts from each half of the 
center are separate and distinct. If the cervical cord be split into a right 
and left half, and one side sectioned at the level of the second cervical ver- 
tebra, then the respiratory movements of that side of the diaphragm cease 
while on the opposide side they continue their rhythm. 

Assuming this view of the quadruple nature of the respiratory centers 
to be correct, there is some difference of opinion as to the exact working 
of the mechanism in its reactions. It is thought that the center may act 
automatically, but normally its automatic discharges of nerve impulses are 


If? R. 96 per 




R. 120 

FIG. 240. The Effect on the Respiratory Rate of Cutting Both Vagi in the Dog. 
The rate of 60 respirations per minute before the section of the nerves drops to 8 per 
minute afterward. The arterial blood-pressure is also shown, the pressure in mm. mer- 
cury is shown in the scale to the left. Compare with figure 182. 

influenced by afferent impulses from the periphery, as well as by impulses 
passing down from the cerebrum. The center is, in other words, both 
automatic and reflex. It will be simplest to discuss its reflex function first. 
Action of Afferent Stimuli on the Respiratory Rhythm. Action 
of the vagi. If both vagi be divided in the neck, the respirations become 
much slower and deeper, figure 240. This may be the case, but to a less 
marked degree, if one of the nerves is divided instead of both. If the cen- 
tral, end of the divided nerve be stimulated with a weak but properly adjusted 


strength of interrupted current, the effect is to quicken the respirations. 
And if the stimuli are properly regulated the normal rhythm of respira- 
tion may be approached. If the stimuli be repeated with stronger currents, 
the breathing is brought to a standstill, sometimes at the height of inspira- 
tion, by tetanus of the diaphragm. Usually, however, stimulation of the 
central end of the divided vagus produces still greater slowing than that 
which follows the division, so that the respirations cease with the diaphragm 
in a condition of complete relaxation, figures 205 and 241. 

The sensory action of the vagus may therefore be to call forth either 
inspiration or expiration the impulses passing up the vagi being factors 
for the production and regulation of the normal variations in respiratory 
rhythm. The fibers of the vagus are stimulated under the following cir- 
cumstances: one set of fibers, those which tend to inhibit expiration and 
to stimulate inspiration, are stimulated at their origin in the lung when the 
lung tissue is under least tension, i.e., in a condition of expiration. The 
fibers which tend to inhibit inspiration and to promote expiration are stim- 
ulated when the lung is fully expanded. The afferent impulses by this view 
are the results of mechanical stimulation, and do not depend upon the 
chemical nature of the gases within the pulmonary alveoli. 

FIG. 241. The Effect of Stimulating the Vagus on Respiratory Rate. The stimulus 
was applied between the points "on" and "off." The inhibition lasts some seconds after 
the stimulus is removed. Time in seconds. The intra-tracheal pressure is recorded 

The Respiratory Action of the Superior Laryngeal Nerves. If the 
superior laryngeal branch of the vagus be divided, which usually produces 
no apparent effect, and the central end be stimulated, the reaction is very 
constant, respirations are slowed, and there is a distinct tendency toward 
expiration, as shown by the contractions of the abdominal muscles. Thus 
the superior laryngeal fibers inhibit inspiration and stimulate expiration, 
while the deep branch of the vagus contains fibers which stimulate inspiration 
and inhibit expiration. 

The superior laryngeal nerves are true expiratory nerves, and are nor- 
mally set in action when the mucous membrane of the larynx is irritated. 
They are not in constant action like the vagi. 

Action of the Glosso-pharyngeal Nerves. It has been ascertained, 
by the researches of Marckwald, that while division of the glosso-pharyngeal 
nerves produces no effect upon respiration, stimulation causes inhibition of 
inspiration for a short period. This action accounts for the very necessary 


cessation of breathing during swallowing. The effect of the stimulation is 
only temporary, and is followed by normal breathing movements. 

Action of Other Sensory Nerves. The respiratory center is in- 
fluenced strongly by afferent nerve impulses having their origin in general 
sensory nerves, particularly the nerves of the skin. Cold water suddenly 
dashed on the skin is followed by a deep inspiration. Stimulation of the 
splanchnics or of the abdominal branches of the vagi produces expiration. 
Stimulation of the isolated sciatic nerve of the dog or of the rabbit causes a 
marked acceleration both of the rate and of the amplitude of the respiratory 
movements, see figure 246 b. This acceleration is due to afferent impulses 
which reach the respiratory center in the medulla over sensory paths, paths 
which are not necessarily special respiratory afferent paths, but rather are 
general afferent paths which affect the respiratory center through their 
numerous collaterals in the brain stem. 

It must be remembered that, although many sensory nerves may on 
stimulation be made to produce an effect upon the respiratory center, yet 
there is no evidence to show that any one of them, except the vagus, is con- 
stantly in action. The vagi indeed are, as far as we know, the normal 
regulators of respiratory movements, yet it is possible reflexly to influence 
the respiratory rate and depth through impulses that may have their origin 
in any sensory part of the body. 

The respiratory center is also influenced by nerve activity of the cerebral 
cortex, psychic activity. This is illustrated by the limited voluntary control 
of the respiratory movements. 

Automatic Action of the Respiratory Centers. Although it has 
been very definitely proved that the respiratory centers may be affected by 
afferent stimuli, and particularly by those reaching them through the vagi, 
there is reason for believing that the center is capable of sending out 
efferent nerve impulses to the respiratory muscles without the action of any 
afferent stimuli. Thus, if the brain be removed above the bulb, respiration 
continues. If the spinal cord be divided immediately below the bulb, the 
facial and laryngeal respiratory movements continue, although no afferent 
impulses can reach the center except through the cranial sensory nerves, and 
these indeed may be divided without producing any effect, when the bulb and 
cord are intact. As has been shown, too, respiration continues when the vagi 
are divided. Isolation of the respiratory center from its sensory relations 
does not destroy respiratory movements so long as the motor paths through 
the phrenic nerves are intact. All of these experiments render it highly 
probable that afferent impulses are not required in order that the respiratory 
centers should send out efferent impulses to the respiratory muscles. The 
center, then, is automatic. 

Method of Automatic Stimulation of the Respiratory Center. The 
respiratory center is capable of working automatically apart from afferent 


impulses, and this fact has been explained by the supposition that it is 
.stimulated to action by the condition of the blood circulating through it. 
When the blood becomes more and more venous the action of the center 
becomes more and more energetic, and if the air is prevented from entering 
the chest, the respiration in a short time becomes very labored. If the 
aeration of the blood is much interfered with, not only are the ordinary 
respiratory muscles employed, but also those muscles of extraordinary in- 
spiration and expiration which have been previously enumerated. Thus, 
as the blood becomes more and more venous, and by venous we mean that 
the blood contains a relatively large amount of carbon dioxide and a dimin- 
ished amount of oxygen, the action of the medullary center becomes more 
and more profound. The question has been much debated as to what 
quality of the venous blood it is which causes this increased activity; whether 
it is its deficiency of oxygen or its excess of carbon dioxide. It has been 
answered to some extent by experiments which offer no obstruction to the exit 
of carbon dioxide, as when an animal is placed in an atmosphere of nitrogen. 
Under these conditions dyspnea occurs, showing that blood which contains 
a diminished amount of oxygen stimulates the cells of the respiratory center. 
On the other hand, if the normal amount of oxygen is supplied while the 
carbon dioxide of the blood is prevented from escaping and thus allowed to 
accumulate in the blood, there is also a great increase in the respiratory 
activity of the center; an excess of carbon dioxide in the blood, flowing 
through the respiratory center, stimulates the cells to greater activity. It 
is highly probable, therefore, that the respiratory centers may be stimulated 
to action both by the absence of sufficient oxygen in the blood circulating 
in it, and by the presence of an excess of carbon dioxide. 

These facts are particularly well supported by the experiments of Zuntz 
who varied the oxygen and the carbon-dioxide content of the air breathed, 
and measured the volume breathed per minute. When the oxygen of the 
air breathed was reduced by 10 to 50 per cent., the air breathed was increased 
only slightly, 5 to 10 per cent. When the oxygen of the air was reduced 
by 60 per cent., the volume of air breathed was increased 30 to 40 per cent., 
and even more. Other observations show us that the oxygen in the blood 
in these experiments will fall in much less per cent, than the reduction in 
the oxygen of the air would lead us to suspect. 

When Zuntz kept the oxygen content of the air about constant, but in- 
creased the carbon-dioxide content, then the amount of air breathed was 
greatly increased. Air containing 18.4 per cent, of oxygen and 11.5 per cent, 
of carbon dioxide caused an increase in the amount breathed per minute 
from 7.5 liters to 32.5 liters. These experiments indicate that within the 
limits of its normal variations in blood the carbon dioxide has a much greater 
influence than oxygen on the irritability of the cells of the respiratory center. 

But this is not all, since it has been observed by Marckwald that the 


medullary center is capable of acting for some time in the absence of any 
circulation and after excessive bleeding. The view taken by this author 
with regard to the action of the center is as follows: The respiratory center 
is set to act by the condition of its metabolism, much in the same way as 
the heart is set to beat rhythmically. When anabolism is completed, katab- 
olism or discharge occurs, and this alternate but crude and spasmodic 
action will occur without a definite blood supply so long as the centers are 
properly nourished and stimulated by their own intercellular fluid. 

It is also apparent that the respiratory center is dependent on the 
character of the blood supply, both as regards quantity and quality of the 
blood. It has been shown that the presence in the blood of the products 
of vigorous muscular metabolism will greatly increase the irritability of the 
respiratory center, even if the blood itself be not particularly venous in 
character as regards its gaseous content. 

The Establishment of Respiratory Movements at Birth. From 
the preceding paragraph it appears that the regulation of the respiratory 
movements is normally due to the automaticity of the respiratory center as 
influenced, first, by the blood flowing through it and, second, by the afferent 
nerve impulses which reach the center. The fetus in the womb is supplied 
by arterial blood from the blood vessels of the mother. The fetus does not 
ordinarily give respiratory movements before birth, but it may be made to 
do so by experimental procedure. At birth the placental circulation is sud- 
denly interrupted, and the blood rapidly increases in venosity until the skin, 
lips, and mucous membranes are very cyanotic in appearance. It is at this 
time that the respiratory center begins its rhythmic discharges, being aroused 
by the direct stimulating effects of the great excess of carbon dioxide in the 
strongly venous blood. The irritability of the respiratory center is also 
increased by the stimulation of the skin by the air, the contact with clothing, 
and by the hands of the nurse. We have already seen that cutaneous 
stimulation leads to an increase in both respiratory rate and amplitude even 
in the adult, a reaction that is more pronounced in the child. The primary 
stimulus for the establishment of the respiratory rhythm at first, then, is the 
venosity of the blood, but this cause is supported by the afferent cutaneous 
impulses producing reflexes through the respiratory center. 

Certain Special Types of Respiration. Whatever the exact quality 
of the venous blood which excites the respiratory center to produce normal 
respirations, there can be no doubt that, as the blood becomes more and 
more venous from obstruction to the entrance of air into the lungs or from 
the blood not taking up from the air its usual supply of oxygen, the respi- 
ratory center becomes either less or more active and excitable. Conditions 
ensue which have received the names Apnea, diminished breathing; Hyper- 
pnea, excessive breathing; Dyspnea, difficult breathing; and Asphyxia, 


Apnea. This is a condition of diminished respiratory movement. When 
we take several deep inspirations in rapid succession by voluntary effort, 
we find that we can do without breathing for a much longer time than usual; 
in other words, several rapid respirations seem to inhibit for a time normal 
respiratory movements. The reason for this partial cessation of respira- 
tion, or apnea, is not that we overcharge our blood with oxygen, as was once 
thought, for Hering has shown that animals in a condition of apnea may 
have less oxygen in their blood than in a normal state, although the carbon 
dioxide is less. It is probable that the cause of apnea is that by rapid in- 
flations of the lungs impulses pass up by the vagi by means of which in- 
spiration is after a while inhibited; or that by the repeated stimulation of 
the center by vagus impulses which result in rapid respiratory movements, 
anabolism is at last arrested. Apnea is with difficulty produced, if at all, 
when the vagi are divided. 

Asphyxia. The condition of stress in the respiratory apparatus brought 
about by insufficient respiratory activity leads to a condition of asphyxia. 
Progressive asphyxiation may be brought on by anything which interferes 
with the normal interchange of the respiratory gases of the blood. 

Asphyxia may be produced by the prevention of the due entry of oxygen 
into the blood, either by direct obstruction of the trachea or other part of the 
respiratory passages, or by introducing instead of ordinary air a gas devoid 
of oxygen, or by interference with the due interchange of gases between 
the air and the blood. 

The respiratory symptoms of progressive asphyxiation may be divided 
into three groups, which correspond with the stages of the condition most 
readily recognized; these are: i, the stage of exaggerated breathing, hyperpnea; 
2, the stage of convulsions, dyspnea; 3, the stage of exhaustion, asphyxiation. 

In the first stage the breathing becomes more rapid and at the same time 
deeper than usual, the inspirations at first being especially exaggerated and 
prolonged. This is soon followed by a similar increase in the expiratory 
efforts being aided by the muscles of extraordinary expiration. This stage is 
usually called hyperpnea. Hyperpnea soon passes into a condition of labored 
breathing in which there is marked increase of the force of the expiratory 
as well as of the inspiratory act, a condition described as dyspnea. All the 
muscles capable of aiding either directly or indirectly in respiration 
are ultimately brought into action. These respiratory convulsions are 
followed by rather sudden onset of paralysis of the respiratory center and 
ultimate death. 

The conditions of the vascular system in asphyxia are: i, more or less 
interference with the passage of the blood through the systemic and the pul- 
monary blood vessels; 2, accumulation of blood in the right side of the heart 
and in the systemic veins; 3, circulation of impure (non-aerated) blood in 
all parts of the body, especially through the respiratory center; 4, great 


slowing of the heart by stimulation of the vagus center from lack of 

It must be kept clearly in mind that the respiratory changes just 
described as characteristic of asphyxiation are the secondary results of the 
primary general tissue asphyxiation. If an animal is deprived of its income 
of oxygen, and its ability to eliminate the product of oxidation, carbon 
dioxide, the nutritive balance around the peripheral tissues is immediately 
disturbed. The result is that tissue metabolism such as occurs is deranged. 
If oxidations are incomplete, intermediary products accumulate and on 
the whole the physiological life of the tissue is rapidly blocked. The 
average organ of the human body can endure only a certain degree of as- 
phyxiation before changes occur which destroy, in whole or in part, the 
protoplasmic organization. Of all the tissues the nervous tissues are most 
susceptible to asphyxiation. The generalized tissues, the epidermis, con- 
nective tissue, etc., are most resistant. Life is jeopardized by injury to the 
weakest point, hence the body as a whole will not recover from complete 
asphyxiation which endures for a time greater than that which the nervous 
tissues will withstand. Stewart, Guthrie, Burns and Pike have set the 
limits very low for this tissue, from 7 to 16.5 minutes. However, incomplete 
asphyxiation is a condition difficult to determine, and the less complete the 
asphyxiation, the greater the probability of recovering the normal tissue 
activity. In all those conditions of life in which accidental asphyxiation 
occurs, it must be assumed that we are dealing with one of partial asphyxia- 
tion, especially in all efforts at resuscitation. 

Cheyne-Stokes' breathing is a rhythmical irregularity in respirations which 
has been observed in various diseases. Respirations occur in groups. At 
the beginning of each group the inspirations are very shallow, but each 
successive breath is deeper than the preceding, until a climax is reached. 
The inspirations then become less and less deep, until they cease altogether 
for a time, after which the cycle is repeated. This phenomenon appears to be 
due to the want of action of some of the usual cerebral influences which pass 
to, and regulate the discharges of, the respiratory center. 

Effects of Vitiated Air. Ventilation. As the air expired from the 
lungs contains a large proportion of carbon dioxide and a minute amount 
of organic matter, it is obvious that if the same air be breathed again and 
again, the proportion of carbon dioxide and organic matter in it will con- 
stantly increase till it becomes unfit to breathe; long before this point is 
reached, however, sensations of uneasiness occur, such as headache, languor, 
and a sense of oppression. It is a remarkable fact, however, that the organ- 
ism after a time adapts itself to a very vitiated atmosphere, and that a person 
soon comes to breathe, without sensible inconvenience, an atmosphere which, 
when he first enters it, feels intolerable. Such an adaptation, however, can 
take place only at the expense of a depression of all the vital functions, which 


must be injurious if long-continued or often repeated. This power of adapta- 
tion is well illustrated by an experiment of Claude Bernard. If a sparrow 
is placed under a bell-glass of such size that it will live for three hours, be 
taken out at the end of the second hour (when it could have survived another 
hour), and a fresh healthy sparrow introduced, the latter will die at once. 

It must be evident that provision for a constant and plentiful supply of 
fresh air, and the removal of that which is vitiated, are of greater importance 
than the actual cubic space per person of occupants. Not less than 2,000 
cubic feet per individual should be allowed in sleeping apartments (bar- 
racks, hospitals, etc.), and with this allowance the air can be maintained at 
the proper standard of purity only by such a system of ventilation as pro- 
vides for the supply of 1,500 to 2,000 cubic feet of fresh air per person per 

Efects of Breathing Gases Other than the Atmosphere. Asphyxiation is 
produced by the direct poisonous action of such gases as carbon monoxide, 
which is contained to a considerable amount in common coal gas. The 
fatal effects often produced by this gas (as accidents from burning charcoal 
stoves in small, close rooms) are due to its entering into combinations with 
the hemoglobin of the blood corpuscles and thus preventing the formation 
of oxyhemoglobin because of the more stable carbon- monoxide hemoglobin. 
The partial pressure of oxygen in the atmosphere may be considerably in- 
creased without much effect in displacing the carbon monoxide, hence this 
is rapidly fatal when breathed. Hydrogen may take the place of nitrogen 
with no marked ill effect, if the oxygen is in the usual proportions. Sul- 
phureted hydrogen destroys the hemoglobin of blood and thus produces oxygen 
starvation. Nitrous oxide acts directly on the nervous system as a narcotic, 
and may also form a compound with hemoglobin. Certain gases, such as 
carbon dioxide in more than a certain proportion, sulphurous acid gases, am- 
monia, and chlorine, produce spasmodic closure of the glottis and prevent 

Alteration in the Atmospheric Pressure. Lower barometric pres- 
sures than the normal occur in high altitudes, for example in mountain 
climbing or in aerial navigation. The susceptibility to decrease in baro- 
metric pressure varies in different individuals. At an altitude of about 
10,000 feet many persons begin to experience mountain sickness, though 
most individuals are not so affected until they ascend to 15,000 feet or 
more. The symptoms that develop are nausea, dizziness, palpitation of 
the heart, headache, and muscular weakness. The oxygen partial pres- 
sure of the atmosphere is reduced to half at about 15,000 feet elevation. 
At this pressure the body begins to show some stress from inability to 
get an adequate quantity of oxygen. The tension of the oxygen in the 
alveolar air is not great enough, see figure 238 showing the relation of the 
partial pressure of oxygen and the percentage of hemoglobin saturation, 


to allow the blood of the pulmonary capillaries to combine with its usual 
quantity of oxygen. There is enough oxygen absorbed, however, to 
satisfy the amount used by the tissues under ordinary circumstances. 
It is only when an extra amount of activity is called for that stress is 
observed at this level. At still greater altitudes the oxygen of the arterial 
blood is further reduced until a level is reached at which the total amount 
of oxygen absorbed by the pulmonary blood is less than that normally 
lost in the tissues. This produces a real tissue oxygen want. The con- 
condition receives the technical name anoxemia. 

Progressive anoxemia sets into activity a number of physiological 
mechanisms which aid the body to absorb its maximum of oxygen from the 
alveolar air. These reactions are called compensatory. They have been 
described by a number of workers in the Medical Division of the United 
States Army who developed a technique for testing the ability of the 

FIG. 2410. The progressive increase of the amount of hemoglobin in the blood 
during a journey from England to the high Andes (Richards). 

human body to withstand low atmospheric pressures in aviation. The 
compensatory factors lead to great increase in respiratory rate, an increase 
in the tidal air, therefore, a great increase in the respiratory minute 
volume of air breathed. The heart rate is also greatly increased thus 
maintaining a higher systolic blood pressure notwithstanding the fact 
that there is vascular dilation, therefore, increased volume of blood flow. 
Also, the percentage of hemoglobin in the blood is increased if the low 
oxygen pressure acts through sufficient time, as in mountain residence, figure 
2410. When the limit of compensation is reached, then the body quickly 
succumbs through the following symptoms. Respiration decreases in rate 
and in amplitude and stops. The blood pressure at first becomes high, 
then falls slowly at first, but more rapidly later to a final low level. The 
heart rate, which is greatly accelerated in the early stage of anoxemia, is 
enormously slowed in the late stages and especially at the time of and 
following the stopping of respiration. It would seem that the lack of 
oxygen at first strongly stimulates the medullary centers of respiration, of 
cardiac acceleration, and of vaso constriction. But in extreme anoxemia 

3 20 


the respiratory center is no longer supported in activity, and the cardiac 
inhibitory center is stimulated to inhibitory spasm. This is shown in 
figure 2416. This figure represents only the terminal effect of anoxemia 
in the dog under chloretone anesthesia. The stopping of respiration is 
shown in the top trace. The blood pressure tracing shows an enormous 
slowing of the heart rate by anoxemial stimulation of the vagus medullary 
center. The proof is found in the rapid heart rate after the vagus nerves 
are both cut. 


FIG. 2416. The effects of extreme anoxemia in the dog. 

The compensatory increase in respiratory rate and volume during 
oxygen want disturbs the factor of carbon dioxide balance in the blood. 
The carbon dioxide is lost more rapidly than usual, hence its concentration 
in the blood is diminished, often from twenty to fifty per cent. That 
carbon dioxide is the chemical stimulator of the respiratory center has 
long been known, but Henderson has more recently given evidence of the 
stimulating effect of carbon dioxide on certain other functions of the 
nervous and muscular mechanisms. He has called the condition of reduced 
carbon dioxide acapnia, and offers the suggestion that lack of sufficient 
carbon dioxide may contribute to the complex of symptoms associated 
with coincident lack of oxygen. 

Men are often subjected to higher than normal barometric pressures in 
caisson work, diving, etc. Paul Bert has found in experimenting with 
animals that the oxygen pressures may be gradually increased to a con- 
siderable extent without marked effect, even to the extent of 8 or 10 atmos- 
pheres, but when the oxygen pressure is increased up to 20 atmospheres the 
oxygen becomes poisonous and the animals experimented upon died with 


severe tetanic convulsions. However, caisson workers often experience 
very severe symptoms, such as bleeding from the nose, dyspnea, vascular 
inco-ordination, etc. These symptoms are due not so much to the great 
increase in pressure as to the release from the pressure. When the 
pressure is released too rapidly, the excess of gases in the tissues and in the 
blood are set free more rapidly than they can be thrown off by excretion 
processes. Gases, as such, gather in the blood vessels and form embolisms 
which occlude the finer vessels. This, of course, produces serious dis- 
turbances in the nutrition of the parts involved. If these parts happen to 
be vital, death may result. 

Resuscitation from Electric Shock and Drowning. Of the numerous 
conditions which lead to accidental asphyxiation, electric shock on the one 
hand, and drowning on the other are of great scientific and practical importance 
in the present day. These special conditions of asphyxiation necessarily in- 
volve problems of general tissue asphyxiation and resuscitation. Under the 
influence of electric shock of sufficient intensity, an immediate result is 
paralysis of the nervous respiratory control, with whatever else may be 
directly or indirectly involved. This condition quickly brings on asphyxia- 
tion with all of its train of perverted functional activity. So also in drowning, 
suspension under water blocks respiratory activity and induces asphyxia- 
tion. Within the last few years careful investigation of this condition has 
been made by Stewart, Guthrie and Pike, by Crile and Dolley, and by 
numerous others. The work has tended to set the time limits of tissue 
asphyxiation after which recovery is impossible or at most incomplete. The 
nerve tissues are most susceptible to injury here, see page 303. Within 
the nervous tissues, the different functional centers manifest different degrees 
of susceptibility. Those immediately involved in the injuries are the re- 
spiratory, vaso-motor, and cardiac regulative centers. If all the activities 
of these nervous mechanisms can be re-established, control of general vis- 
ceral reactions will be insured. The delicate functional activity of the 
higher or cortical regions of the brain are even more susceptible to asphyxia- 
tion, and recover more slowly if at all. 

In the condition of drowning there are no highly important special 
injuries. In electric shock on the other hand, there may be a series of 
local injuries from electric burns, etc. These may injure only the point of 
contact between the surface of the body and the electric conductor, but it 
is perfectly possible that the injury may be intense on some deep-seated 
vital structure. In such cases, recovery of the respiration or of the circula- 
tion will not necessarily insure ultimate success in the efforts to revive the 

Considering the fact that the nervous tissue cannot be safely recovered 
beyond the limit of 15 minutes (this is a fair maximum average from our 
most reliable authorities) it follows that immediate and careful steps must 


be taken to eliminate the conditions producing tissue asphyxiation, i.e., 
to re-establish both respiration and circulation. Artificial respiration in one 
form or another is the first aid to be given in drowning, and in other types of 
asphyxiation, since the technique is equally effective after the lungs are 
emptied of fluid. The method at present most relied upon is that of Schafer 
which includes both the artificial respiration and indirect heart massage. 
The procedure to be followed in Schafer' s method in condensed statement 
is given as follows by Dolley: 

" The patient is rolled upon his belly, the face turned to one side, and the 
arms are extended as straight forward as possible. The extension of the 
arms is a very important improvement, introduced by the Commission, on 
the original Schafer method. The operator kneels straddling the patient's 
thighs and facing his head; he places his palms on the muscles of the small 
of the back with the fingers spread over the lowest ribs. Then holding his 
arms straight, he swings forward so that his weight is gradually brought to 
bear upon the subject. This should take from two to three seconds, and must 
not be violent. It compresses both the chest and the abdomen. The result 
is that not only is the chest compressed from front to back, but the pressure 
on the abdominal viscera tends to force the diaphragm upward. The air is 
forced out of the lungs, expiration. The operator then immediately swings 
back to his starting position. Through their elasticity the chest walls ex- 
pand and air is inspired. A two-second interval should follow the forced 
expiration so that the rate is from twelve to fifteen a minute. The method 
not only accomplishes safely and easily ventilation of the lungs, but it must 
affect a fair amount of compression and relaxation of the heart, especially 
in young or thin individuals. This so-called indirect heart massage, which 
will be more emphasized later, is a valuable stimulant to a failing heart." 
Artificial respiration should be kept up for from two to four hours. A 
slight but temporary circulation of the blood may produce a partial oxidation 
which only very slowly recovers sufficient vital activity to bring the nerve 
centers up to the automatic and reflex level of activity required. 

Some cases of so-called drowning are in reality death from cardiac failure. 
Any hope of resuscitation in this type depends upon vigorous indirect 
cardiac massage. This is accomplished more effectively in the above method 
of artificial respiration by allowing the palms of the hands to slide around 
to the sides of the body, presssing near the ends of the free ribs. In this 
position it is easy to give pressure with the finger tips under the ribs and 
against the heart. In extreme, and perhaps in surgical cases, direct massage 
may be given. 1 

1 Fuller discussion of the conditions involving drowning and the procedure look- 
ing toward recovery are available in the following references: C. C. Guthrie, Blood- 
vessel Surgery, chapter on Resuscitation, page 300. Report of the Commission on 
Resuscitation from Electric Shock, W. B. Cannon, Chairman. Medical Handbook 
for the Use of Lighthouse Vessels, etc., published by the U. S. Public Health and 
Marine-Hospital Service. D. H. Dolley, On Resuscitation, Bulletin of the University 
of Missouri, Medical Series, No. 4. 



Apparent recuperation with the re-establishment of both normal and 
respiratory activity may occur, yet later stoppage will come about. Prolonged 
asphyxiation leaves the body and tissues so clogged with carbon dioxide 
and other waste products, that the renewal of the vital activity of the nervous 
centers is under a weakened condition. In such cases it is highly necessary 
to prolong artificial respiration. Even after asphyxiation of short duration 
it may be some hours or even days before the body is brought back to its 
normal level of functional efficiency. 


As the heart, the aorta, and pulmonary vessels are situated in the air- 
tight thorax, they are exposed to a certain alteration of pressure when the 
capacity of the latter is varied during respiration. The disturbance of pres- 
sure which occurs during inspiration causes, first, a .decrease in the intra- 

FIG. 242. Diagram of an Apparatus Illustrating the Effect of Inspiration upon the 
Heart and Great Vessels within the Thorax. I, The thorax at rest; II, during inspiration; 
D represents the diaphragm when relaxed; D', when contracted (it must be remembered 
that this position is a mere diagram), i. e., when the capacity of the thorax is enlarged; H, 
the heart; V, the veins entering it, and A, the aorta; Rl,Ll, the right and left lung; T, the 
trachea; M, mercurial manometer in connection with pleura. The increase in the capacity 
of the box representing the thorax is seen to dilate the heart as well as the lungs, and so to 
pump in blood through V, whereas the valve prevents reflux through A. The position of 
the mercury in M shows also the suction which is taking place. (Landois.) 

thoracic pressure, a decrease which affects all the organs of the thorax the 
lungs, the great blood-vessels, the heart. The expansion of the elastic lungs 
counterbalances this change in pressure in part, but it never does so entirely, 
since part of the pressure within the lungs is expended in overcoming their 
elasticity. The amount thus used up increases as the lungs become more 
and more stretched, so that the intrathoracic pressure during inspiration, as 


far as the heart and great vessels are concerned, never quite equals the intra- 
pulmonary pressure, and at the conclusion of inspiration is considerably 
less than the atmospheric pressure. It has been ascertained that the amount 
of the pressure used up in the way above described varies from 5 to 7 mm. of 
mercury in ordinary inspiration, to 30 mm. of mercury at the end of a deep 
inspiration. So it will be understood that the pressure to which the heart 
and great vessels are subjected diminishes as inspiration progresses, and at 
its summit is less by from 7 to 30 mm. than the normal atmospheric pres- 
sure, 760 mm. of mercury. It will be understood from the accompanying 
diagram how an increase in the volume of the thorax will have the effect of 
pumping blood into the heart from the veins. During inspiration the pres- 
sure outside the heart and great vessels is diminished, and they, by virtue of 
their elasticity, have therefore a tendency to expand and to diminish the intra- 
vascular pressure. The diminution of pressure within the veins passing 
to the right auricle and within the right auricle itself, will draw the blood 
into the thorax, and so assist the circulation. This suction action of the 
thorax is the cause of the slight negative pressure of the ventricles previously 
described. The effect of more blood in the right auricle will, cateris paribus, 
increase the amount passing through the right ventricle, and through the 
lungs into the left auricle and ventricle, and thus into the aorta. This all 
tends to increase the blood-pressure. The effect of the diminished pressure 
upon the pulmonary vessels will also help toward the same end, an increased 
flow through the lungs, so that, as far as the mechanical effects on the heart 
and its veins are concerned, inspiration increases the blood-pressure in the 
arteries. The effect of inspiration upon the aorta and its branches within 
the thorax would be, however, contrary; for as the external pressure is dimin- 
ished, the vessels would tend to expand, and thus to diminish the tension of 
the blood within them, but, inasmuch as the relative variation in pressure 
on the large arteries is slight, the diminution of arterial tension caused by 
this means will be insufficient to counteract the increase of blood-pressure 
produced by the effect of inspiration upon the volume of discharge of the 
veins of the chest, and the balance of the whole action would be in favor of 
an increase of blood-pressure during the inspiratory period. When a blood- 
pressure tracing is taken at the same time that the respiratory movements 
are being recorded, it will be found that, although, speaking generally, the 
arterial tension is increased during inspiration, the maximum of arterial 
tension does not correspond with the acme of inspiration, figure 243. In 
fact, at the beginning of inspiration the pressure continues to fall for a brief 
moment, then gradually rises until the end of inspiration, and continues to 
do so for a moment after expiration has commenced. For explanation of 
the influence of heart rate in this variation of blood-pressure, associated 
with the respiratory movement, see page 212. 

In ordinary expiration all this would be reversed, but if the abdominal 


muscles are violently contracted, as in extraordinary expiration, the same 
relative effect would be produced as by inspiration. The immediate effect 
during inspiration of the diminished intra-thoracic pressure upon the pul- 
monary vessels is to produce an initial dilatation of both artery and veins, 
and this delays for a moment the passage of blood toward the left side of 
the heart, resulting in an initial fall in the arterial pressure, but the fall of 
blood-pressure is immediately followed by a steady rise, since the flow is 
increased by the initial dilatation of the vessels. The converse is the case 
with expiration. As, however, the pulmonary veins are more easily di- 
latable than the pulmonary artery, their greater distensibility increases the 

FIG. 243. Comparison of Blood-pressure Curve with Curve of Intra-thoracic Pressure. 
(To be read from left to right.) a is the curve of blood-pressure with its respiratory 
undulations, the slower beats on the descent being very marked; b is the curve of intra- 
thoracic pressure obtained by connecting one limb of a manometer with the pleural cavity. 
Inspiration begins at i and expiration at e. The intra-thoracic pressure rises very rapidly 
after the cessation of the inspiratory effort, and then slowly falls as the air issues from 
the chest; at the beginning of the inspiratory effort the fall becomes more rapid. (M. 

flow of blood as inspiration proceeds, while during expiration, except at its 
beginning, this property of theirs acts in the opposite direction, and diminishes 
the flow. Thus, at the beginning of inspiration the diminution of blood 
pressure, which commenced during expiration, is continued, but after a time 
the diminution is succeeded by a steady rise. The reverse is the case with 
expiration, i.e., there is at first a rise and then a fall of blood pressure. 

As regards the effect of expiration, the capacity of the chest is diminished 
and the intra-thoracic pressure returns to the normal, which is still slightly 
below the atmospheric pressure. The effect of this on the veins is to in- 
crease their extravascular and so their intravascular pressure, and to di- 
minish the flow of blood into the left side of the heart. This will, of course, 
react to decrease the general blood-pressure. Ordinary expiration does not 
produce a distinct obstruction to the circulation, as even when the expiration 
is at an end the intra-thoracic pressure is less than the atmospheric pressure. 
The effect of violent expiratory efforts, however, does have a distinct action 


in obstructing the current of blood through the lungs, as seen in the con- 
gestion in the exaggerated condition of straining, this condition being pro- 
duced by pressure on the entire group of pulmonary vessels. 

There are other mechanical factors, such, for example, as the effect of 
the abdominal movements, both in inspiration and in expiration, upon the 
arteries and veins within the abdomen and of the lower extremities. Also 
the influence of the varying intrathoracic pressure upon the pulmonary 
vessels, which ought to be taken into consideration. The effect of the 
abdominal movements during inspiration is twofold. On the one hand, 
blood is sent upward into the chest by compression of the vena cava inferior; 
on the other hand, the passage of blood downward from the chest through 
the abdominal aorta, and upward in the veins of the lower extremity, is to 
a certain extent obstructed. 

3 2 7 


1. Respiratory Rate in Man. Count your respirations for from 2 
to 4 minutes while sitting quietly, and determine the average number per 
minute. Repeat the counting after standing for 5 minutes, and after 
brisk exercise. These determinations involve the element of conscious- 
ness, under which condition it is difficult for a person to breathe with his 
normal rate and depth. 

Make a series of determinations of respiratory 
rates of persons who are sitting quietly but uncon- 
scious of your determinations. Count the rates in 
a number of persons of different ages; where possible, 
take into consideration height, weight, etc. Tabu- 
late the results for a comparison and for future 

2. The Character of Respiratory Movements 
in Man. A number of instruments have been 
devised for measuring human respiratory move- 
ment, many of which measure the change in 
diameter of the chest in respiratory movement. 
Adjust one of these, for example Burdon-Sander- 
son's stethograph, to the thorax, and record the 
movement of the receiving tambour on a smoked- 

paper kymograph which travels at the rate of i 

, m, . , j FIG. 244. Change in 

cm. per second. Inis record, called a stethogram, Diameter of the Body in 

will exhibit the respiratory rate, the relative time of Respiration, Costal Type. 
^, >. , , , ^, a. Outline of the body in 

the linspiratory and expiratory phases, and the forced expiration. In the 

character of each. heavy continuous line, b, 

3. The Actual Change of Diameter in the Chest 
in Respiration. Use a caliper provided for the pur- ordinary inspiration and 

, i , ,. f , the inner margin that of 

pose and measure the dorso- ventral diameter of the ordinary expiration. c t 

chest at a series of points along the sternum, taking Contour of forced inspira- 
j. J _ 1 , . , ^ ,. Al . , tion. (After Hutchinson.) 

the reading at the height of the inspiratory phase 

and of the expiratory phase in ordinary respiration. Repeat the measure- 
ment in forced respiration. Map the results on millimeter paper, as 
indicated in figure 244. 

Repeat these measurements in the transverse diameter at the first, 
fifth, and tenth ribs. 

Using the thoracograph, figure 245, record the outline of the cross 
section of the chest at the level of the mammae, tenth rib, and the umbili- 
cus, showing the volume changes in the following four positions: (i) 
Ordinary expiration, (2) ordinary inspiration, (3) forced expiration, (4) 
forced inspiration, see figure 246. 


4. The Volume of Air Breathed by Man. Determine the average vol- 
ume of air breathed per respiration, using Hutchinson's spirometer, figure 
235, set the instrument at the zero point, exhale into the instrument 

through the tube, using all possible care 
Ml to breathe with your normal rate and 


; ' ~ ; depth. Better results will be obtained 

dgfe|&j by taking the average from sets of ten 

j ? consecutive expirations into the instru- 

^^ ment. From the average of the volume 

per respiration, and the average number 
of respirations per minute, determined 
in Experiment i, calculate the amount 
of air breathed per hour and per day. 
5 . Vital Capacities. Using the spiro- 
meter as in the preceding experiment, 
set the instrument at zero and exhale 
into it: 

a. Begin with the fullest possible 
inspiration and exhale the greatest pos- 
sible amount of air from the lungs. This 
is known as the vital capacity. 

b. Beginning at the end of an ordi- 
FIG. 245. Thoracograph of Deufestcl. nai T expiration exhale into the instru- 
ment the greatest possible amount. 

This is called the reserve air. 

c. Following ordinary inspiration exhale into the instrument until you 
reach the ordinary state of expiration. This involves the conscious fixing 
of two points in the respiratory act, namely, the summit of inspiration and 
of expiration, which are ordinarily automatically adjusted by the body. 
The error of the determination is therefore great. It is better to make this 
measurement in sets of ten, as in the preceding experiment, and take the 
average. This reduces the error. This quantity of air is known as the 
tidal air. One can measure the tidal air and the reserve air together, check 
them against the sum of the two, as in a and b. 

d. The sum of the tidal and reserve air taken from the vital air will 
leave the amount which one may inspire over and above that in the chest 
at the end of ordinary inspiration. This is called complemental. The 
complemental can be measured by inspiring the air from the spirometer, 
but this is not good hygienic practice where large numbers are using the 
same instrument, unless the instrument be thoroughly cleaned before the 
inspiration is taken. 

6. The Respiratory Pressure in Man. Measure there spiratory 
pressure, the variation in pressure of the air in the air-passages, by means 



of the mercury manometer or by a graduated Marey's tambour. Connect 
a piece of gas tubing with the proximal limb of the mercury manometer and 
provide it with a glass mouthpiece. Insert this mouthpiece well back into 
the cavity of the mouth, closing the lips firmly about it, keeping the 
pharynx relaxed. Note the variations in pressure at the height of ordinary 
inspiration and expiration through the nasal passages. Repeat with 
forced inspiration and expiration, close the nasal passages, and make the 

FIG. 246. Chart showing transverse section of the chest at the level of the 
mamma of a distance runner, age twenty-one, height, 5 feet, n inches, net weight, 140 
T^nnrie ]? x i ? ordinary expiration; Ex*, forced expiration; In 1 , ordinary inspiration; 


In 2 , forced inspiration. 

Scale J. 

maximal expiratory and inspiratory effort. The manometer may be ad- 
justed to write on the smoked paper or read directly. 

7. Demonstration of Carbon Dioxide in Expired Air. Arrange 
two flasks, as in figure 246, filling each one-third full of baryta-water, or 
lime-water. Close the lips around the mouthpiece of the apparatus and 
inhale and exhale the air through it. The inspired air will come through 
a, the expired air out through b. The baryta water in b will quickly 
become clouded with a white precipitate of barium carbonate while that 
in a will remain clear or only very slightly clouded, showing the excess of 
carbon dioxide in expired air. 

8. Quantitative Determination of Carbon Dioxide and Oxygen in 
Inspired Air and in Expired Air. Inspired Air. Fill a gas-analysis 
apparatus, the Guthrie or any modern modification of the Haldane or the 
Orsat analyzer, with air from outside the laboratory. Read the volume 



at room temperature and pressure. Wash the sample back and forth 
through the potash bulb as directed ten times and read for absorption of 
the carbon dioxide. Next wash in ten per cent, pyrogallic acid in potas- 
sium hydroxide until constant readings show that all oxygen is absorbed. 

FIG. 246a. Apparatus for Demonstrating Excess of CO 2 in Expired Air. Flasks filled 

with lime-water. 

The nitrogen residue is calculated by difference. Compute the per- 
centages of carbon dioxide, oxygen and nitrogen. 

Expired Air. Exhale ten expirations controlled by one-way valves 
into an ordinary respirometer or a Tissot apparatus. Now fill the Guthrie 
apparatus with a sample of this expired air and analyze as before, first for 

FIG. 2466. Change in Respiration on Stimulating the Central End of the Sciatic 
Nerve. The rate is sharply increased and the amplitude more than doubled. The 
stimulation is between the points marked on and off, time in seconds. The inspiratory 
movement following the stimulation was greater than the limit of the recording tambour. 

carbon dioxide, then for oxygen; compute the percentage of each gas, 
including nitrogen. The expired air will usually be found to have lost 
from 4 to 5 per cent, of oxygen and have gained a little more than that 
quantity of carbon dioxide. 


From the percentages obtained in these experiments, and the volume 
of air breathed per unit of time, computed in Experiment 4 above, deter- 
mine the amount of carbon dioxide exhaled per hour per kilogram of 
weight for your own body. Compute also the amount of oxygen con- 
sumed per kilo per hour; per square meter of surface per hour. 

9. The Rate and Character of the Respiratory Movements in the 
Mammal. a, The rate of respiration can be best determined by direct 
count per minute, an effort being made to maintain as nearly normal 


c d 

FIG. 24.6c. Oxygen and carbon dioxide analyzer, Guthrie form. 
FIG. 246^. Receiver for air sample, Guthrie form. 

conditions as possible. Make the determinations on a cat, a dog, and 
a guinea-pig, b, The character of the respiratory movements can be 
recorded by one of the various forms of stethograph adapted to the size of 
the animal, or by the arrangement shown in figure 233. It is necessary to 
make the determination with an animal under the influence of an anes- 

10. The Nervous Mechanism of Respiratory Movements. a. The 
Ejffett of Stimulating Cutaneous Nerves. Use a small dog or a cat for 
this experiment; anesthetize and introduce a tracheal tube with a side 


branch adapted for measuring the variations of pressure during respira- 
tion. Connect the free limb of the tracheal tube with an ether apparatus 
and adjust to secure constant anesthesia. Connect the side branch of the 
tracheal tube with a Marey's recording tambour of medium size and sup- 
plied with a comparatively delicate membrane. The amplitude of the 
movements of the tambour may be regulated by a screw compress on a 
connecting tube. Arrange an induction coil with platinum electrodes in 
the usual manner for stimulating by means of the interrupted current. 
Record the results of the experiment along with the variations of blood- 
pressure on a continuous-paper kymograph; the instrument should be 
supplied with a time signal, a stimulating signal, etc. 

Now stimulate the skin of the abdominal region, the groin, with a com- 
paratively strong medium induction current, figure 2466. Dissect out the 
sciatic nerve, cut it, stimulate the central end with a mild to medium 
strength of current. The stimulus should be graduated carefully, for 
there is often such a great increase in respiratory rate and volume that the 
animal may become overanesthetized. 

b. The Effect of Stimulating the Vagus Nerve. Isolate and stimulate 
the vagus nerve with a medium strength of stimulus. The effect is usually 
complete inhibition of respiratory movements. By means of graduated 
stimuli one may demonstrate the accelerator effects from the stimulation 
of the vagus. Stimulate also the superior laryngeal, and compare with the 
effects of stimulating the whole vagus. 

c. The Effect of Cutting the Vagus Nerves. Isolate both vagus nerves 
and section them as nearly at the same moment as possible. Be sure to 
mark on the tracing the exact moment at which the nerves are cut. This 
experiment should be performed with every accessory condition as con- 
stant as possible, and the animal should not be disturbed for one or two 
minutes so that the effects of the section will be recorded, figure 240. The 
result is always a marked deepening and slowing of the respiratory 

d. The Effect of Stimulating the Central End of the Vagus. Upon stimu- 
lating the central end of the vagus after section, the respiration rate will be 
inhibited as in b, showing that the vagus nerves carry afferent respiratory 
fibers, figure 241. 

e. The Effect of Stimulation of the Phrenic Nerves. Isolate the right 
phrenic nerve at its origin from the brachial plexus and stimulate it with a 
medium strength of stimulus. Upon stimulating the nerve the diaphragm 
will remain in contraction and the record will show that the thorax is in the 
inspiratory phase. The phrenic is therefore a simple motor nerve. 

Section this nerve and note the change in the character of respiratory 
movements; make direct observations on the diaphragm, examining from 
the abdominal side. 


ii. Demonstration of Apnea, Dyspnea, and Asphyxia. Produce 
deep anesthesia, then disconnect the ether bottle and connect the tracheal 
tube with a hand bellows. Produce deep and forced artificial respiration 
for ten to twenty seconds. Stop artificial respiration; the animal will 
remain quiet and without any effort at breathing. This is the condition 
of apnea. Allow the animal to recover its normal respiratory rate and 
again produce deep anesthesia. Now clamp off the tracheal tube so that 
the animal can no longer receive air and leave it so until death. As the 
blood becomes more and more venous there will first be a marked increase 
in the respiration rate and depth. This is known as hyperpnea. This 
stage is followed by one of increasing respiratory amplitude in which the 
accessory respiratory muscles not previously active are brought into 
forcible contractions, both inspiratory and expiratory phases are now 
forced, dyspnea. The movements continue to increase, and the muscles 
of the neck, larynx, mouth, and nostrils now take part. There is a 
rather sudden decrease in the respiratory movements, an extension of the 
limbs, and gasping movements, after which the animal remains quiet, 
death being produced by asphyxia. 

12. Respiratory Exchange and Calorimetry. Indirect calorimetry is 
made the basis for determining the metabolic rate in man and mammals. 
Measurement of the oxygen intake and of the carbondioxide output under 
standard conditions suffices for the computation from the data of the 
metabolic rate of heat production per kilo or per square meter of surface 
per hour. This principle is used in the rapid methods of human clinical 

Generally a man is made to exhale into a large collecting chamber 
(Tissot apparatus), or breathe through a closed chamber (rebreather) 
provided with absorbers and either one-way valves or a pump to circulate 
the air of the chamber. 

In man the test is made with the body at maximum rest. Test (i) 
after a 12 hour fast; (2) measure the height in centimeters and weight 
in kilos; (3) provide 20 to 30 minutes complete relaxation lying at rest; 
(4) measure systolic and diastolic blood pressures and mouth tempera- 
ture after the rest period; (5) Adjust the face mask and run the test of 
oxygen consumption. Use a modified Henderson rebreather or a Bene- 
dict filled with excess of pure oxygen, or a Tissot apparatus. Continue 
the test for ten minutes or more. In the dog use a rebreather type of 
apparatus of adapted size. Attach a face mask to a ten kilo dog trained 
to the experiment. Record all rebreather movements. 

From the data for man, compute the metabolic rate per square meter 
per hour for man by DuBois' formula. 

In man the surface area in sq. cm. = The Weight in kilos - 425 X the 
Height in cm. - 725 X a constant 71.84. 


Compute the rate per kilo per hour for the dog. Compare with the 
rate per kilo on man and explain the difference observed. 

13. Gases of Arterial and Venous Blood. Tissue respiration is inti- 
mately dependent on the capacity of the blood to carry oxygen and carbon 
dioxide by chemical fixation, chiefly by the respiratory pigment hemo- 
globin. Measure the gaseous content of arterial and venous blood 
simultaneously drawn from a dog under local analgesia. Draw the 
samples under petrolatum and analyze promptly for the three gases, 
carbon doxide, oxygen and nitrogen, in a Van Slyke apparatus, page 303. 
Also consult the Journal of Biological Chemistry, vol. 30, page 347, and 
vol. 33, page 127. 


ALL tissues of the body produce certain chemical changes as a result of 
their protoplasmic activity. But in certain cells chemical elaborations have 
come to be the chief function, the cells have been differentiated in that direc- 
tion, and the name secreting tissue or gland tissue is applied. The end result 
of metabolism in gland tissue is the extrusion on the free borders of the cells 
of the products of their metabolism. The products are known as secretions 
and the process itself is the act of secretion. Certain secretions which are 
in the nature of waste products to the body as a whole, such as urine in the 
kidney, are often called excretions, but the use of the term should not be allowed 
to confuse the general similarity of this to other secretions as regards the 
physiological changes involved in its production. 

Most secretions accomplish some definite office in the economy of the 
body. Those that are discharged on some free mucous surface, as the saliva, 
gastric juice, tears, etc., are called external, or true secretions, or merely secre- 
tions. Substances that are discharged back into the blood stream later to 
influence the metabolism of tissues other than the ones which produced them 
are called internal secretions. 

Gland cells, like other tissues, draw their nourishment from the blood 
and lymph. The product or secretion of gland cells may, in fact usually 
does, contain some of the substances found in the blood, but there are also 
present new materials elaborated by the cells, and even where the same sub- 
stance exists both in the secretion and in the blood and lymph it can make 
its appearance in the secretion only under the control of the protoplasm of 
the gland cells. The saliva secreted by the salivary cells, for example, con- 
sists of about 98 to 99 per cent, water containing in solution small quantities 
of certain salts, also found in the lymph, and a small percentage of the en- 
zyme, ptyalin. This enzyme is peculiar to the salivary secretion and is manu- 
factured by the salivary-cell protoplasm. As is well known, it acts vigorously 
in extreme dilution, hence the high per cent, of water in the secretion. The 
passage of water from a solution as concentrated as blood plasma to a solu- 
tion as dilute as saliva requires a high amount of osmotic energy, an amount 
that can be supplied only from the chemical energy liberated by the cell in 
its protoplasmic activity. After the removal of the special organ by which 
each secretion is manufactured, the secretion is no longer formed. Cases 
sometimes occur in which the secretion continues to be formed by the natural 



organ, but, not being able to escape toward the exterior, on account of some 
obstruction, is reabsorbed and accumulates in the blood. It may be dis- 
charged from the body in other ways; but these are not instances of true 
vicarious secretions, and must not be so regarded. 

Organs and Tissues of Secretion. The principal secreting organs 
are the following: i. The serous and synovial membranes; 2. the mucous 
membranes with their special glands, e.g., the buccal, gastric, and intestinal 
glands; 3. the salivary glands and pancreas; 4. the liver; 5. the mam- 
mary glands; 6. the lachrymal glands; 7. the kidney and skin; 8. the 
testes and ovaries, and 9. thyroid, supra-renal, etc. 

The special structure and functions of the secreting organs will be given 
in greater detail in the chapters which immediately follow. The general 
types of structure and general conditions that influence the functions are 
introduced at this point. 

Structural Types of Secreting Organs. Serous and Synovial Type. 
The serous membranes form closed sacs lining visceral cavities like the 
abdominal, pericardial, or pleural cavities. The organs are, as it were, 
pushed into this sac and carry before them an investment of membrane. The 
serous membranes consist of a single layer of flattened polygonal cells 
resting on a supporting membrane of connective tissue, supporting a rami- 
fication of blood vessels, lymphatics, and nerves. 

In some instances, i.e., synovial membranes, the secreting layer is in- 
creased by finger-like elevations. This type of secreting organ produces 
ordinarily only enough secretion to keep the surface moist. 

The Mucous Type. The mucous tracts, and different portions of each 
of them, present certain structural peculiarities adapted to the functions 
which each part has to discharge; yet in some essential characters the mucous 
membrane is the same, from whatever part it is obtained. In all the princi- 
pal and larger parts of the several tracts it presents an external layer of epithe- 
lium, situated upon a basement membrane, and beneath this a stratum of 
vascular tissue of variable thickness, containing lymphatic vessels and nerves. 
The vascular stratum, together with the basement membrane and epithelium, 
in certain cases is elevated into minute papillae and villi, in others depressed 
into involutions in the form of glands. But in the invaginations of the secret- 
ing membrane of gland cells, the supporting basement membrane and the net- 
work of capillaries are still retained in their relative position. With increas- 
ing complexity of involution the simple mucous membrane becomes packed 
away in an apparently solid mass. The equivalent of a large amount of 
secreting surface is thus condensed into a small space. In the process of in- 
vagination some differentiation occurs in that certain of the gland cells be- 
come conducting and have their secretory activity somewhat reduced. 

Secreting Glands. The secreting glands present, amid manifold 
diversities of form and composition, a general plan of structure; but all are 



constructed with particular regard to the arrangement of the cells which has 
just been described. 

Secreting glands are classified according to certain structural types, as: 
i. The simple tubular gland, A, figure 247, examples of which are furnished 
by the follicles of Lieberkuhn, and the tubular peptic glands of the stomach. 
They are simple tubes of mucous membrane, the walls of which are lined with 

FIG. 247. Plans of Extension of Secreting Membrane by Inversion or Recession in the 
Forms of Cavities. A, Simple glands, viz., g, straight tube; h t sac; i, coiled tube. B, 
Multilocular crypts; k, of tubular form; /, saccular. C, Racemose or saccular compound 
gland; m, entire gland, showing branched duct and lobular structure; , a lobule, detached 
with o, branch of duct proceeding from it. D, Compound tubular gland. (Sharpey.) 

secreting cells arranged as an epithelium. To the same class may be re- 
ferred the elongated and tortuous sudoriferous glands. 

2. The compound tubular glands, D, figure 247, form another division. 
These consist of main gland tubes, which divide and subdivide. Each gland 
may be made up of the subdivisions of one or more main tubes. The ulti- 
mate subdivisions of the tubes are sometimes highly convoluted. They are 


formed of epithelium of various forms, supported by a basement membrane. 
The larger tubes may have an outside coating of fibrous areolar or muscular 
tissue. The salivary glands, pancreas, Brunner's glands, kidney, testes, with 
the lachrymal and mammary glands, are examples of this type, but present 
more or less marked variations among themselves. 

3. The racemose glands, in which a number of vesicles or acini are arranged 
in groups of lobules, C, figure 247. The Meibomian follicles are examples 
of this kind of gland. There seem to be glands of mixed character, com- 
bining some of the characters of the tubular with others of the racemose type; 
these are called tubulo-racemose or tubulo-acinous glands. The acini are 
formed by a kind of fusion of the walls of several vesicles, which thus combine 
to form one large cavity with recesses lined or filled with secreting cells. The 
smallest branches of the gland-ducts sometimes open into the centers of these 
cavities; sometimes the acini are clustered round the extremities or by the 
sides of the ducts; but, whatever secondary arrangement there may be, all 
have the same essential character of rounded groups of vesicles containing 
gland cells, and opening by a common central cavity into minute ducts, 
which in the large glands converge and unite to form larger and larger 
branches, and at length one common trunk which opens on a free surface. 

The Process of Secretion. The process of secretion is dependent 
upon the activity of the secreting cells. In the case of the water and salts the 
physical processes of filtration and diffusion may play a part. 

The chemical processes constitute the process of secretion properly so 
called, as distinguished from mere transudation spoken of above. In the 
process of secretion various materials which do not exist as such in the blood 
are manufactured by the agency of the gland cells, using as a nutrient fluid 
the blood or, to speak more accurately, the lymph which fills the interstices 
of the gland textures. 

Evidences in favor of this view are: i. That gland cells are constituents 
of all glands, however diverse their outer forms and other characters, and 
they are placed in all glands on the surfaces or in the cavity whence the secre- 
tion is poured. 2. That certain materials of secretions are visible with the 
microscope in the gland cells before they are discharged. Thus, granules 
probably representing the precursors of the ferments of the pancreas may 
be discerned in the cells of that gland. Granules of uric acid are found in 
the cells of the kidneys of birds and fish, and fatty particles, like those of milk, 
in the cells of the mammary gland. 

Certain secreting cells, like the cells of the sebaceous glands, appear to 
develop, grow, and attain their individual perfection by appropriating nutri- 
ment from the fluid exuded by adjacent blood vessels and building it up so 
that it shall form part of their own substance. In this perfected state the cells 
subsist for some brief time and then appear to dissolve, wholly or in part, and 
yield their contents to the peculiar material of the secretion. The changes 


which have been noticed from actual experiment in the cells of the salivary 
glands, pancreas, and peptic glands will be described more fully in the 
chapter on Digestion. 

Discharge of secretions from the glands may either take place as soon as 
formed, or the secretion may be long retained within the gland or its ducts. 
The former is the case with the sweat glands. But the secretions of those 
glands whose activity of function is periodical are usually retained in the cells 
in an undeveloped form during the period of the gland's inaction. 

When discharged into the ducts, the further course of secretions is affected: 

(1) partly by the pressure from behind; the fresh quantities of secretion pro- 
pelling those that were formed before. In the larger ducts, its propulsion is 

(2) assisted by the contraction of the walls. All the larger ducts, such as 
the ureter and common bile duct, possess in their coats plain muscular fibers; 
they contract when irritated, and sometimes manifest peristaltic movements. 
Rhythmic contractions in the pancreatic and bile ducts have been observed, 
and also in the ureters and vasa deferentia. It is probable that the contrac- 
tile power extends along the ducts to a considerable distance within the sub- 
stance of the glands whose secretions can be rapidly expelled. Saliva and 
milk, for instance, are sometimes ejected with much force. 

Circumstances Influencing Secretion. The principal conditions 
which influence secretion are variations in the quantity of blood and varia- 
tions in nerve impulses passing to the gland cells over secretory nerve fibers. 

An increase in the quantity of blood traversing a gland, as in nearly all 
the instances before quoted, coincides generally with an augmentation of its 
secretion. Thus the mucous membrane of the stomach becomes florid when, 
on the introduction of food, its glands begin to secrete. The mammary 
gland becomes much more vascular during lactation. All circumstances 
which give rise to an increase in the quantity of material secreted by an organ 
produce, coincidently, an increased supply of blood. But we shall see that a 
discharge of saliva may occur under extraordinary circumstances without in- 
crease of blood supply, and so it may be inferred that this condition of in- 
creased blood supply is not absolutely essential to the immediate formation 
of secretion, but that it favors the prolonged activity of glands. 

Influence of the Nervous System on Secretion. The process of 
secretion is largely regulated through the nervous system. The exact mode 
in which the influence is exhibited must still be regarded as somewhat obscure. 
In part it exerts its influence by increasing or diminishing the quantity of 
blood supplied to the secreting gland, in virtue of the power which it exercises 
over the contractility of the smaller blood vessels. It also has a more direct 
influence, as is described at length in the case of the submaxillary gland, upon 
the secreting cells themselves. This may be called trophic influence. Its 
influence over secretion, as well as over other functions of the body, may be 
excited by causes acting directly upon the nervous centers, upon the nerves 


going to the Secreting organ, or upon the nerves of other parts. In the latter 
case a reflex action is produced. Thus the impression produced upon the 
sensory nerves by the contact of food in the mouth leads to afferent 
nerve impulses to the secretory center in the central nervous system, im- 
pulses which are reflected by the nerves supplying the salivary glands, 
and produce, through these, a more abundant secretion of the saliva. 

Through the nerves, various conditions of the brain also influence the 
secretions. Thus, the thought of food may be sufficient to excite an abun- 
dant flow of saliva. And, probably, it is the mental state which excites the 
abundant secretion of urine in hysterical paroxysms, as well as the perspira- 
tions, and occasionally diarrheas, which ensue under the influence of terror, 
and the tears excited by sorrow or excess of joy. The quality of a secretion 
may also be affected by mental conditions, as in the cases in which, through 
grief or passion, the secretion of milk is altered, and is sometimes so changed 
as to produce irritation in the alimentary canal of the child. 


THE term digestion includes those changes taking place in the body which 
bring the materials of the food into such condition that they may be taken up 
by the blood and lymphatic vessels and thus rendered available for the metab- 
olism of the tissues. In the process the foods are rendered more soluble 
and more diffusible. Certain bodies which are already soluble and diffusible 
are converted into forms which are more available for the tissues; as an ex- 
ample, cane-sugar, although both soluble and diffusible, cannot be readily 
used by the body until it is converted from a disaccharide to a monosaccha- 
ride. In fact, few of the food materials are fit for immediate use when taken 
into the body and are therefore practically useless until digested. 


We have been accustomed to classify foods into certain main groups, 
chiefly according to their chemical character, as follows: 

Proteins. Such as albumin, myosin, gluten, casein, etc.; gluco-protein, 
nucleoprotein, etc.; gelatin, elastin, etc. These furnish nitrogen in avail- 
able form. 

Carbohydrates. Such aG starch, dextrose, cane-sugar, etc. 

Fats. Such as tristearin, tripalmitin, triolein. 

Minerals. The various salines found in animal and vegetable food. 


The classes of foods just enumerated usually exist in mixtures rather than 
in simple forms, as, for example, a beef roast contains a representative of each 
of the five classes enumerated, though it is composed chiefly of water, pro- 
teins, and fats. The human body is capable of using materials of a great 
variety of forms, but most of these have the foods mixed in such a way as to give 
representatives of each of the classes above in certain general proportions. 

Nitrogenous Foods. The Flesh of Animals, e.g., beef, veal, mutton, 
pork, bacon, ham, chicken, eggs, milk, etc., are typical nitrogenous foods. 

Of these, beef and eggs are richest in nitrogenous matters, containing 
about 20 per cent. Mutton contains about 18 per cent., veal 16 . 5, and pork 
10. Beef is firmer, more satisfying, and is supposed to be more strengthen- 
ing than mutton, whereas the latter is more digestible. The flesh of young 
animals, such as lamb and veal, is less digestible and less nutritious. Pork 
contains a large amount of fat and is, therefore, comparatively indigestible. 












Meat (beef round) 

71 6 

22 6 

2 8 

i 3 


Meat (pork loin) 

52 .0 


30 . i 

i .0 


i, 580 

Fish (king salmon) 




i, 080 

Eggs. . . . 



IO . S 

I . O 


Milk (cow's) 

87 .0 

7 . 7 

4 . O 

5. o 

O . 7 

72 ; 

Milk (human) 

80 7 

2 O 


6 o 

O 2 

Cheese (American) 



7C . Q 

o . ? 

7 .4. 

2.0 <; ^ 



I . O 

8 1; o 

7 .O 

2 60 <c 

Bread (white) 

33 2 

IO . O 

I . 7 


I . O 

.2 < < 

Bread (corn) 

7.8 . 


4 . 7 

46 . 3 

2 . 2 

20 e; 


12 7. 


O 3 

7O O 

O 4 

6 10 

Oatmeal . 

7 . 1 


7 2 

67. < 

I . O 


Beans (dry) 


22 . <; 


CQ . 6 

7 . e 

60 (? 

Potatoes (white) 

78 1 

2 2 

O I 

18 4 

I O 


Potatoes (sweet) . . . 

60 . o 


o . 7 

27 .4. 

I . 2 


Fruit (strawberries) 

GO .4 

I . O 





Watermelon (edible portion) 



. 2 

6. 7 



Meat contains: (i) Muscle proteins, chiefly myosin, blood proteins, colla- 
gen (from the interstitial fibrous connective tissue), elastin (from the elastic 
tissue), as well as traces of hemoglobin. (2) Fats, including the lipoids 
lecithin and cholesterol. (3) Extractives, some of which are agreeable to 
the palate and others weakly stimulating. These are divided into the 
non-nitrogenous: glycogen, dextrose, lactic acid, inosit, etc., and into the 
nitrogenous: consisting chiefly of creatin, and the purine bases. (4) Salts, 
chiefly chlorides and phosphates of potassium, calcium, and magnesium. 
(5) Water, the amount of which varies from 15 per cent, in dried bacon to 
39 in pork, 51 to 53 in fat beef and mutton, and 72 per cent, in lean beef and 






Beef lean ... . . . ... 


IQ . 1, 


C. I 

Beef fat 




4 .4 

Mutton lean 





Mutton -fat .... 


12 .4 


7 . C 





4 7 

Pork fat . 













2 T . O 


I . 2 

White fish . . 



2 . 

I . O 


16. i 

5. c 

I 4 

Eels (very rich in fat) 
Oysters. . 




II .72 

2 .42 



The flesh of nearly all animals has been occasionally eaten, and we may 
presume that except for difference of flavor, etc., the average composition, 
aside from the fat, is nearly the same in most cases. 

Milk. Milk is the entire food of young animals, and contains all the 
elements of a typical diet. Albuminous substances are represented in the 
form of ca.seinogen, and serum or lactalbumin; fats in thecream; carbohydrates 
in the form of lactose or milk-sugar; salts, chiefly as calcium phosphate; and 
water. From milk we obtain a number of food preparations, such as cheese 
rich in protein and fat, butter and cream, buttermilk rich in proteins and 
peculiarly well adapted for invalid diet, and whey which contains all the sugar, 
salts and the albumin. 







Milk (cow} . . 

4 * 

7 . Q 

C . 2 




4 . I 

O . 7 





4 I 

26 7 




Cheese ski m 

44 8 

6 ^ 



Cheese cheddar 


3 1 i 

4 . ^ 


Eggs. The yolk and albumin of eggs of oviparous animals bear the 
same relation as food for the embryos that milk bears to the young of mam- 
malia, and affords another example of the natural admixture of the various 
alimentary principles. The proteins of eggs are ovalbumin and ovoglobulin 
and phosphoprotein, the mtellin of the yolk. In addition to the three com- 
mon fats there is a yellow fatty pigment, lutein (lipochrome), lecithin, and 
cholesterol, a small quantity of dextrose, and inorganic salts, chiefly calcium, 
potassium, sodium, chlorides, and phosphates. 








2O 4. 

i 6 




2Q 7 

i 3 

r 2 

Legumes are used by vegetarians as the principal source of the nitrogen of 
the food. Those chiefly used are peas, beans, lentils, etc.; they contain a 
nitrogenous substance called legumin, allied to albumin. Legumes contain 
about 25.30 per cent, of this nitrogenous body and twice as much nitrogen 
as wheat. Nuts also form a very nutritious article of diet. 

Carbohydrate Foods. Bread, made from ground grain obtained from the 
various so-called cereals, viz., wheat, rye, maize, barley, rice, oats, etc., is 
the direct form in which the carbohydrate is supplied in an ordinary diet. 
It contains starch, dextrin, and a little sugar. It also contains gluten, com- 
posed of vegetable proteins, and a small amount of fat. 









r i 

i .6 

2 . "? 

3 7 

Flour. . . . 

10 8 

70 8 ? 

2 O 

I 7 

I r 

Various articles besides bread are made from flour, e. g., spaghetti, maca- 
roni, etc. Dextrin and a small amount of dextrose are present in bread, 
particularly in the crust. 

Vegetables, especially potatoes. They contain starch and sugar. In 
cabbage, turnips, etc., the salts of potassium are abundant. 

Fruits contain sugar and organic acids, tartaric, malic, citric, and others. 

Sugar, chiefly saccharose, used pure or in various sweetmeats. 

Oils and Fats. The substances supplying the oils and fats of the food 
are chiefly butter, bacon and lard, suet (beef and mutton fat), and vegetable 
oils. These contain the fats olein, stearin, and palmitin. Butter contains 
some tributyrin, while vegetable oils, as a rule, contain no stearin. 

Mineral or Inorganic Foods. The salts of the food. Nearly all the 
substances in the preceding classes contain a greater or less amount of the 
salts required in food. Green vegetables and fruit contain certain salts, 
chiefly potassium. Sodium chloride is an essential food; it is contained in 


nearly all solid foods, but so much is required that it has also to be taken as a 
condiment. Potassium salts are found in muscle, nerve, and in meats 
generally, and in potatoes and other vegetables. Calcium salts are contained 
in eggs, blood of meat, wheat, and vegetables. Iron is contained in hemo- 
globin, in milk, eggs, and vegetables. 

Liquid Foods. Water is essential to life, and from two to two and a 
half pints a day must be consumed in addition to that taken mixed with solid 
food. Of the non-alcoholic substances which may be adored to it for flavoring 
purposes, such as tea, coffee, cocoa, etc., the last can alone be considered to 
have a certain food value, as it contains fats, albuminous material, and starch, 
the other constituents of such substances being a volatile oil, an alkaloid 
caffeine, and tannic acid. The food value of alcoholic beverages, which has 
long been a subject of controversy, as now generally agreed is but slight. 
Beer, wines, and spirits contain ethyl alcohol, the amount varying from i . 5 
to 4 . 5 per cent, in beer to 40 to 80 per cent, in spirits. 

The Effect of Cooking on Foods. In general terms cooking may 
be said to render food more easily digestible, both directly and indirectly, 
through increased palatability. Subjecting food to high degrees of heat also 
serves to kill parasites, such as trichinae and the various tapeworms, which 
may be present and alive in raw meats. In the case of meats various methods 
of cooking are employed. In roasting, the meat in bulk is subjected to a 
high temperature in an oven for a short time, 250 C. for 15 minutes, followed 
by a somewhat lower temperature, 175 C., until the cooking is completed. 
This causes a coagulation of the outer layers of albumin so that the juices 
of the meat are retained until the center of the mass is cooked to the stage 
desired, i. e- raised to a temperature of 63 to 65 C- when medium done. 
In boiling, the meat is first immersed in boiling water for a time and then 
the cooking continues at a lower temperature. In a broth, the extractives 
may be obtained by heating the meat in water for a long period. Such a 
broth contains the flavoring and the stimulating extracts of the meat, but 
is of only slight nutritive value. A temperature below the coagulation point, 
at 60 C., will extract more nutritive protein substance. For small pieces 
of meat, broiling practically serves the same purpose as does roasting for 
larger pieces. Frying, as usually employed, is the least serviceable method 
of preparation, since the fat or other oily material used so permeates the 
food as to render it difficult of penetration by the digestive juices. 

Cooking produces upon vegetables the necessary effect of rendering them 
softer, so that they can be more readily broken up in the mouth. It also 
causes the starch grains to swell and burst, and so aids the digestive fluids 
in penetrating into their substance. The albuminous matters are coagulated, 
and the gummy, saccharine, and saline matters are removed. The con- 
version of flour into dough is effected by mixing it with water, and adding a 
little salt and a certain amount of yeast. Yeast consists of the cells of an 


organized ferment (Torula cerevisice)\ this plant in its growth changes by 
ferment action the sugar produced from the starch of the flour, and a quantity 
of carbon dioxide and some alcohol is formed. The gas together with the 
action of heat during baking causes the dough to rise, and the gluten being 
coagulated, the bread sets as a permanently vesiculated mass. 


The Enzymes. The digestive process involves both mechanical and 
chemical changes. The former are secured by the crushing and grinding 
in the mouth, together with the mixing and kneading that come from the 
peristalses of the stomach and intestine. The chemical changes are the 
most important factors of the digestive process. The various secretions that 
are poured into the mouth, stomach, and intestines all contain substances 
which react on the foods to render the latter more soluble. The special 
agency in each secretion is the presence of representatives of the chemical 
groups known as enzymes. These enzymes, or unorganized ferments, are 
the essential factors in the secretions which produce the chemical changes 
in the foods. Their predominant action is one of hydrolytic cleavage; that 
is, the substance acted upon takes up water and then splits into two different 
substances, usually of the same class. The chemical nature of the en- 
zymes is as yet undetermined because of the difficulty of getting absolutely 
pure specimens. Their mode of action is at present regarded in the nature 
of catalysis. That is to say, the enzymes by their presence facilitate reactions 
that would otherwise take place but very slowly. Practically all are formed 
in the glands as zymogens, which bear the same relation to enzymes as 
fibrinogen does to fibrin; they are transformed to enzymes by the proper 
stimulus, but never exist as such in the glands. 

Each enzyme has a special point of temperature at which it acts best, and 
any change in the temperature retards its action; the action is suspended at 
a definite point of low temperature, but the enzyme is not destroyed by cold. 
The action is suspended at a somewhat higher temperature, and at a still 
higher point the enzyme is destroyed. Some enzymes act only in an alka- 
line medium, being destroyed in an acid medium, and vice versa. Others 
act in either alkaline, or neutral, or acid media. Enzymes are hindered in 
their action by the accumulation of the products of their activity. Most of 
them cease acting altogether when these products reach a certain concen- 
tration, but will begin acting again on the removal of these products or if 
the mixture be simply diluted. 

The quantity of the enzyme determines the rapidity of the action, but not 
the amount; a small quantity will digest as much as a large quantity, but will 
take longer. The enzymes are not used up in the course of their activity, 
as far as can be seen, and do not seem to undergo any change in their 


Enzymes are more or less specific in their action. That is, each enzyme 
is supposed to produce its change in only one particular substance, as in 
starch, maltose, protein, fat, etc. An enzyme that can cause cleavage of the 
starch molecule will not act on fat or protein or even on other members of 
the starch group. This specific action is doubtless expressive of a definite 
relation between the structure of the enzyme and the substance acted on. 

An interesting fact as to enzyme action is its reversibility a phenomenon 
now well known and well established for carbohydrates and fats. Kastle 
and Lowenhart have shown that lipase, which acts to split neutral fats into 
fatty acid and glycerin, will also produce a synthesis, at least of butyric 
acid and alcohol into ethylbutyrate. Taylor and Robertson in independent 
papers have recently made the far-reaching discovery that the protein 
molecule can be synthesized by the agency (apparent reversible action) of 

Enzymes are classified either according to the chemical nature of their 
action or according to the class of substances on which they act; the former 
classification is more logical, but the latter is more convenient and more 
generally used. 



Ptyalin of saliva, and amylopsin of pancreatic juice, change starch to mal- 
tose. Maltase in the saliva, and pancreatic juice in the small intestine, 
change maltose to dextrose. Lactase splits lactose to galactose and dextrose, 
and invertase splits cane-sugar to levulose and dextrose in the small intestine. 
Li poly tic. 

Steapsin or lipase, found in the pancreatic juice, splits neutral fats into 
glycerin and fatty acid. 

Pepsin of the gastric secretion, and trypsin of the pancreatic secretion, 
change proteins to proteoses and peptones, trypsin breaking the protein down 
to simpler nitrogenous products. Erepsin of the intestine splits peptones to 
simpler products. 

Rennin of the gastric juice coagulates milk. 

Enterokinase of the intestinal juice converts trypsinogen to trypsin. 
(Thrombokinase of the blood is of this class.) 


The food is received into the mouth and is subjected to the action of the 
teeth and tongue, being at the same time mixed with the first of the digestive 
juices, the saliva. It is then swallowed, and, passing through the pharynx 
and esophagus into the stomach, is subjected to the action of the gastric 
juice, the second digestive juice. Thence it passes into the small intestines, 
where it meets with the bile, the pancreatic juice, and the intestinal juices, all 


of which exercise a digestive influence upon the portion of the food not already 
digested and absorbed. In the large intestine some further digestion and 
absorption take place, and the residue of undigested matter leaves the body 
in the form of feces. 

Mastication. The act of mastication is performed by the biting and 
grinding movement of the lower range of teeth against the upper. The 
simultaneous movements of the tongue and cheeks assist by crushing the 
softer portions of the food against the hard palate and gums, thus supple- 
menting the action of the teeth, and by returning the morsels of food to the 
action of the teeth as they are squeezed out from between them until they 
have been sufficiently chewed. 

The simple up-and-down or biting movements of the lower jaw are per- 
formed by the temporal, masseter, and internal pterygoid muscles, the action 
of which in closing the jaws alternates with that of the digastric and other 
muscles passing from the os hyoides to the lower jaw, which open the jaws. 
The grinding or side movements of the lower jaw are performed mainly by 
the external pterygoid muscles, the muscle of one side acting alternately with 
the other. When both external pterygoids act together, the lower jaw is 
pulled directly forward, so that the lower incisor teeth are brought in front 
of the level of the upper. 

The act of mastication is voluntary. It will suffice here to state that the 
afferent nerves chiefly concerned are the sensory branches of the fifth, ninth, 
and tenth, and the efferent are the motor branches of the fifth and the twelfth 
cerebral nerves. 

The act of mastication is much assisted by the saliva, which is secreted by 
the salivary glands in largely increased amount during the process. The 
intimate incorporation of the saliva with the food is termed insalivation. 

The Salivary Glands. The glands which secrete the saliva in the 
human subject are the salivary glands proper, the parotid, the submaxil- 
lary, and the sublingual, and numerous smaller bodies of similar structure 
and with separate ducts, which are scattered thickly beneath the mucous 
membrane of the lips, cheeks, soft palate, and root of the tongue. 

Histological Structure. The salivary glands are compound tubular 
or tubulo-racemose glands. They are made up of lobules. Each lobule con- 
sists of the branchings of a division of the main duct of the gland, which 
are generally more or less convoluted toward the extremities, that form the 
alveoli, or proper secreting parts of the gland. The salivary secreting cells 
are of cubical or columnar form and are arranged around a central canal. 
The granular appearance frequently seen in the salivary cells is due to the 
numerous zymogen granules which they contain. 

During the rest period the cells are larger, highly granular, with obscured 
nuclei and smaller lumen. During activity the cells become smaller and 
their contents more opaque. 



When the mucous type of gland is secreting, or on stimulation of the nerve, 
mucinogen is converted into mucin, the cells swell up, appear more transparent 
and stain deeply in logwood, figure 249. After stimulation, the cells become 
smaller, more granular, and more easily stained from having discharged their 
contents, and the nuclei appear more distinct. 

Nerves of large size are found in the salivary glands. They are princi- 
pally contained in the connective tissue of the alveoli, and certain glands, 
especially in the dog, are provided with ganglia. Some nerves have special 

FIG. 248. 

FIG. 249. 

FIG. 248. Section of the Submaxillary Gland of a Dog, Resting Stage. Most of the 
alveolar cells are large and clear, being filled with the material for secretion (in this case, 
mucigen), which obscures their protoplasm; some of the cells, however, are small and 
protoplasmic, forming the crescents seen in most of the alveoli. (Ranvier.) 

FIG. 249. Section of a Similar Gland after a Period of Activity. The mucigen has 
been discharged from the mucin-secreting cells, which consequently appear shrunken and 
less clear. Both the cells and the alveoli are much smaller, and the protoplasm of the cells 
is more apparent. The crescents of Gianuzzi are enlarged, c, Crescent cells; g, mucus- 
secreting cells; /, lumen of alveolus. (Ranvier.) 

endings in Pacinian corpuscles, some supply the blood vessels, and others 
penetrate the basement membrane of the alveoli and end upon, but not in, 
the salivary cells. 

The blood vessels form a dense capillary network around the ducts of the 
alveoli, being carried in by the fibrous trabeculae between the alveoli, in which 
also the lymphatics begin by lacunar spaces. 

The Nervous Mechanism of the Secretion of Saliva. The secretion 
of saliva is under the control of the nervous system. Under ordinary con- 
ditions it is excited by the stimulation of the peripheral branches of two 
nerves, the gustatory or lingual branch of the inferior maxillary division 
of the fifth nerve, and of the glosso-pharyngeal, which are distributed to the 
mucous membrane of the tongue and pharynx conjointly. The stimulation 
occurs on the introduction of sapid substances into the mouth, and the 
secretion is brought about in the following way: From the terminations of 
the above-mentioned sensory nerves distributed in the mucous membrane 


an impression is conveyed upward (afferent) to the special nerve center 
situated in the medulla oblongata which controls the process, and by it is 
reflected to certain nerves supplied to the salivary glands, which will be pres- 
ently indicated. In other words, the center, when stimulated to action by 
the sensory impressions carried to it, sends out impulses along efferent or 
secretory nerves supplied to the salivary glands. These cause the saliva to be 
secreted by, and discharged from, the gland cells. Other stimuli, however, 
besides that of the food, and other sensory nerves than those mentioned 
may reflexly produce the same effects. For example, saliva may be caused 
to flow by irritation of the mucous membrane of the mouth with mechanical, 
chemical, electrical, or thermal stimuli, also by the irritation of the mucous 
membrane of the stomach in some way, as in nausea which precedes vomit- 
ing when some of the peripheral fibers of the vagi are irritated. Stimulation 
of the olfactory nerves by smell of food, of the optic nerves by the sight of it, 
and of the auditory nerves by the sounds which are known by experience to 
accompany the preparation of a meal may also stimulate the nerve center to 
action. In addition to these, as a secretion of saliva follows the movement 
of the muscles of mastication, it may be assumed that this movement stimu- 
lates the secreting nerve fibers of the gland, direct or reflexly. From the fact 
that the flow of saliva may be increased or diminished by mental states, it 
is evident that impressions from the cerebrum also are capable of stimulating 
the center to action or of inhibiting its action. 

Influence of Nerves on the Submaxillary Gland. The submaxillary 
gland has been the gland chiefly employed for the purpose of experimentally 
demonstrating the influence of the nervous system upon the secretion of 
saliva, because of the comparative facility with which the gland, with its blood 
vessels and nerves, can be exposed to view in the dog, rabbit, and other 

The chief nerves supplied to the gland are: (i) the chorda tympani, a 
branch given off from the facial in the canal through which it passes in the 
temporal bone; and (2) branches of the sympathetic nerve from the plexus 
around the facial artery and its branches to the gland. The chorda, figure 
250, passes downward and forward, under cover of the external ptery- 
goid muscle, and joins the lingual or gustatory nerve, proceeds with it for a 
short distance, and then passes along the sub maxillary- gland duct, 
giving branches to the submaxillary ganglion, and sending others to 
terminate in the superficial muscles of the tongue. It consists of fine medul- 
lated fibers which lose their medullae in the gland. If this nerve be exposed 
and divided anywhere in its course from its exit from the skull to the gland no 
immediate result will follow, nor will stimulation either of the lingual or of 
the glosso-pharyngeal produce a flow of saliva. But if the peripheral end 
of the divided nerve be stimulated, an abundant secretion of saliva ensues, 
and the blood supply is enormously increased by dilatation of the arteries. 


The veins may even pulsate, and the blood contained within them is more 
arterial than venous in character. 

When, on the other hand, the stimulus is applied to the sympathetic fila- 
ments (mere division producing no apparent effect), the arteries contract, 
and the blood stream is in consequence much diminished; and only a sluggish 
stream of dark blood escapes from the veins. The saliva, instead of being 
abundant and watery, becomes scanty and tenacious. If both chorda tym- 
pani and sympathetic branches be divided, the gland, released from nervous 
control, may secrete continuously and abundantly (paralytic secretion). 

FIG. 250. Diagram showing the distribution of the cranial and sympathetic secretory 
and vase-motor nerves for the parotid and submaxillary glands. The post-ganglionic 
neurones are in black; the pre-ganglionic neurones including the central neurone of the 
sympathetic path are in red. (Diagram based on figures by Sheldon, Brubaker, and 

The abundant secretion of saliva which follows stimulation of the chorda 
tympani is not merely the result of a nitration of fluid from the blood vessels, 
in consequence of the largely increased circulation through them. This is 
proved by the fact that, when the main duct is obstructed, the pressure within 
may considerably exceed the blood-pressure in the arteries ; and also that, when 
some atropine has been previously injected into the veins of the animal ex- 
perimented upon stimulation of the peripheral end of the divided chorda pro- 
duces all the vascular effects as before, without any secretion of saliva accom- 
panying them. Again, if an animal's head be cut off, and the chorda be 
rapidly exposed and stimulated with an interrupted current, a secretion of 


saliva ensues for a short time, although the blood supply is necessarily absent. 
These experiments serve to prove that the chorda contains two sets of nerve 
fibers: one set, V as o- dilator , which, when stimulated, act upon a local vaso- 
motor center for regulating the blood supply, inhibiting its action, and 
causing the vessels to dilate, and so producing an increased supply of blood 
to the gland; while another set, which are paralyzed by injection of atropine, 
directly stimulate the cells themselves to activity, whereby the cells secrete 
and discharge the constituents of the saliva which they produce, the secretory 
nerves. These latter fibers very possibly terminate on the salivary cells 
themselves. If, on the other hand, the sympathetic fibers be divided, stimu- 
lation of the tongue by sapid substances, or electrical stimulation of the trunk 
of the lingual or of the glosso-pharyngeal, continues to produce a flow of 
saliva. From these experiments it is evident that the chorda^ tympani nerve 
is the principal nerve through which efferent impulses proceed from the center 
to excite the secretion of this gland. 

The sympathetic nerve also contains two sets of fibers, v as o- constrictor 
and secretory. But the flow of saliva upon stimulating the sympathetic is 
scanty, and the saliva itself viscid. At the same time the vessels of the gland 
are constricted. The secretory fibers may be paralyzed by the administra- 
tion of atropine. 

Nerves of the Parotid Gland. The nerves which influence secretion 
in the parotid gland are branches of the facial (lesser superficial petrosal) 
and of the sympathetic. The former nerve, after passing through the otic 
ganglion, joins the auriculo- temporal branch of the fifth cerebral nerve, and, 
with it, is distributed to the gland. The nerves by which the stimulus ordi- 
narily exciting secretion is conveyed to the medulla oblongata are, as in the 
case of the submaxillary gland, the fifth and the glosso-pharyngeal. The 
pneumogastric nerves convey a further stimulus to the secretion of saliva 
when food has entered the stomach; the nerve center is the same as in the case 
of the submaxillary gland. 

Changes in the Gland Cells. The method by which the salivary 
cells produce the secretion of saliva appears to be divided into two stages, 
which differ somewhat according to the class to which the gland belongs, viz., 
whether to (i) the true salivary or to (2) the mucous type. In the former 
case it has been noticed, as already described, that during the rest which 
follows an active secretion the lumen of the alveolus becomes smaller, the 
gland cells larger and very granular. During secretion the alveoli and their 
cells become smaller, and the granular appearance in the latter to a consider- 
able extent disappears, and at the end of secretion the granules are confined 
to the inner part of the cell nearest to the lumen, which is now quite distinct, 
figure 251. 

It is supposed from these appearances that the first stage in the act of 
secretion consists in the protoplasm of the salivary cell taking up from the 


lymph certain materials from which it manufactures the elements of its own 
secretion, and which are stored up in the form of granules in the cell during 
rest; the second stage consists of the actual discharge of these granules, with 
or without previous change. The granules are zymogen granules, and repre- 
sent the chief substance of the salivary secretion, ptyalin. In the case of the 
submaxillary gland of the dog, at any rate, the sympathetic nerve fibers ap- 
pear to have to do with the first stage of the process, and when stimulated 
the protoplasm is extremely active in manufacturing the granules, whereas 
the chorda tympani is concerned in the production of the second act, the 
actual discharge from the cells of the materials of secretion, together with a 

FIG. 251. Alveoli of True Salivary Gland. A, At rest; B, in the first stage of secretion; 
C, after prolonged secretion. (Langley.) 

considerable amount of fluid. The latter is an actual secretion by the 
protoplasm, as it ceases to occur when atropine has been subcutaneously 

In the mucus-secreting gland, the changes in the cells during secretion 
have been already spoken of. They consist in the gradual production by the 
protoplasm of the cell of a substance called mucigen, which is converted into 
mucin, and discharged on secretion into the canal of the alveoli. The muci- 
gen is, for the most part, collected into the inner part of the cells during rest, 
pressing the nucleus and the small portion of the protoplasm which remains 
against the limiting membrane of the alveoli. 

The process of secretion in the salivary glands is identical with that of 
glands in general. The cells which line the ultimate branches of the ducts 
are the agents by which the special constituents of the saliva are formed. The 
material which they have incorporated within themselves, which is doubtless 
a product of the metabolism of the protoplasm of the cells, is given up again 
almost at once in the form of a fluid, secretion, which escapes from the ducts 
of the gland. The cells themselves undergo diminution in the mass of their 
protoplasm, which is again renewed in the intervals of the active exercise of 
the functions. The source whence the cells obtain the materials for the con- 
struction of secretion is the blood plasma, which is filtered off from the circu- 
lating blood into the interstices of the glands, as in all living tissues. 


Saliva. Saliva, as it commonly flows from the mouth, is the mixed 
secretion of the salivary glands proper and of the glands of the buccal mucous 
membrane and tongue. When obtained from parotid ducts, and free from 
mucus, saliva is a transparent watery fluid, the specific gravity of which 
varies from i . 004 to i . 008 and in which, when examined with the micro- 
scope, are found floating a number of minute particles, derived from the 
secreting ducts and vesicles of the glands. In the impure or mixed saliva 
are found, besides these particles, numerous epithelial scales separated from 
the surface of the mucous membrane of the mouth and tongue, and the so- 
called salivary corpuscles, discharged probably from the mucous glands of the 
mouth and the tonsils. These subside when the saliva is collected in a deep 
vessel and left at rest. They form a white opaque sediment leaving the 
supernatant fluid transparent and colorless, or with a pale bluish-gray tint. 
Saliva also contains various kinds of micro-organisms (bacteria). The 
saliva, when first secreted, appears to be always alkaline in reaction; the 
alkalinity is about equal to o . 08 per cent, of sodium carbonate, and is due 
to the presence of disodium phosphate, Na 2 HPO 4 . 

The presence of potassium sulpho cyanide, KCNS, in saliva may be shown 
by the blood-red coloration which the fluid gives with a solution of ferric 
chloride, Fe 2 Cl 6 , and which is bleached on the addition of a solution of 
mercuric chloride, HgCl 2 , but not by hydrochloric acid. 


In 1,000 Parts. 

Water 994 . 2 

Solids 5.8 

Mucus and epithelium 2.2 

Soluble organic matter (ptyalin) 1.4 

Potassium sulphocyanide o . 04 

Salts . 2.20 

Saliva from the parotid is less viscid; less alkaline, the first few drops 
discharged in secretion being even acid in reaction; clearer, although it may 
become cloudy on standing from the precipitation of calcium carbonate by 
the escape of carbon dioxide; and more watery than that from the submaxil- 
lary. It has, moreover, a less powerful action on starch. Sublingual saliva 
is the most viscid, and contains more solids than either of the other two, but 
has little diastasic action. 

Rate of Secretion and Quantity of Saliva. The rate at which saliva 
is secreted is subject to considerable variation. When the tongue and muscles 
concerned in mastication are at rest, and the nerves of the mouth are subject 
to no unusual stimulus, the quantity secreted is not more than sufficient with 
the mucus to keep the mouth moist. During actual secretion the flow is 
much accelerated. 



The quantity secreted in twenty-four hours varies greatly, but is at least 
i liter. 

Function of Saliva. The purposes served by saliva are mechanical 
and chemical. 

Mechanical. (i) It keeps the mouth in a due condition of moisture, 
facilitating the movements of the tongue in speaking and in the mastication 
of food. (2) It serves also in dissolving sapid substances, and renders them 
capable of exciting the nerves of taste. (3) But the principal mechanical 
purpose of the saliva is that, by mixing with the food during mastication, it 

FIG. 252. Showing the variation of the rate of secretion of saliva, second line from 
the top, and variation of blood pressure, top line. At a, an injection of o . 2 mgr. pilocar- 
pine. At &, 50 c.c. oxygenated blood was injected into the jugular vein. (Jonescu.) 

makes a soft pulpy or creamy mass such as may be easily swallowed. To 
this purpose the saliva is adapted both by quantity and quality. For, speak- 
ing generally, the quantity secreted during feeding is in direct proportion 
to the dryness and hardness of the food. 

Chemical. The chemical action which the saliva exerts upon the food in 
the mouth is to convert the starchy materials which it contains into soluble 
starch and then into sugar. This power the saliva owes to the enzyme 
ptyalin. Certain investigators have of late asserted that saliva contains 
another enzyme, known as maltase, which has the power of splitting the di- 
saccharides into monosaccharides, or maltose into dextrose. The action of 
this ferment is certainly very limited. The conversion of the starch under 
the influence of the ferment into sugar takes place in several stages, and in 
order to understand it a knowledge of the structure and composition of 
starch granules is necessary. A starch granule consists of two parts : an en- 


velope of cellulose, which does not give a blue color with iodine except on 
addition of sulphuric acid, and of granulose, which is contained within, and 
which gives a blue color with iodine alone. Briicke states that a third body 
is contained in the granule, which gives a red color with iodine, viz., erythro- 
granulose. The granulose swells up on boiling, bursts the envelope, and the 
whole granule is more or less completely converted into a paste or gruel 
which is called gelatinous starch. 

When ptyalin acts upon boiled starch, it first changes the latter, by hydrol- 
ysis, into soluble starch, or amidulin; this is more limpid and more like a true 
solution, though it still gives the blue coloration on the addition of iodine. 
This stage is very brief, only thirty seconds being sometimes required in labo- 
ratory experiments to render a stiff starch paste completely fluid when a few 
drops of saliva are added at body temperature. This rapidity of action is of 
great importance, as under proper conditions of mastication practically all 
the boiled starch of the food ought to enter the stomach as soluble starch. 
When the starch has not been previously boiled, the envelope of cellulose 
retards the action of the ptyalin to a very marked degree. 

Soluble starch. 

Erythro-dextrin. Maltose and iso-maltose. 

Achroo-dextrins. Maltose and iso-maltose. 

The further stages of hydrolytic cleavage result in the formation of a 
variable mixture of maltose and iso-maltose with a series of dextrins, but ap- 
parently never result (in laboratory experiments) in the complete conversion 
of the dextrins into sugars. Gradually, as the starch is converted, the blue 
coloration with iodine is replaced by a purplish-red and finally by a red 
color: the latter color is produced by ery thro- dextrin (so called from the 
color). In the later stages no coloration is obtained with iodine, and for this 
reason the dextrins formed are known as achroo- dextrins', there are probably 
several of these, but they have not yet been sufficiently isolated. As sugar 
appears very early in the process, even at the stage of erythro-dextrin, and 
gradually increases in amount, it is generally concluded that maltose is 
formed early in the decomposition of the starch molecule. The process is 
usually represented schematically as above. 

The sugars formed are maltose (C 12 H 22 O n ) and a closely allied sugar 
known as iso-maltose. A small percentage of dextrose has been found by 
some observers, and this is due to the action of maltase. Maltose is allied 


to saccharose or cane-sugar more nearly than to glucose; it is crystalline; its 
solution has the property of polarizing light to the right to a greater degree 
than solutions of glucose (3 to i); it is not so sweet, and reduces copper sul- 
phate less easily. It can be converted into glucose by boiling with dilute 
acids and by the action of the enzyme maltase present in saliva. 

According to Brown and Heron, the reactions may be represented thus : 
One molecule of gelatinous starch is converted by the action of an amylolytic 

ferment into n molecules of soluble starch. 

One molecule of soluble starch = (C 12 H 20 O 10 ) 10 +8H 2 O, which is further con- 
verted by the ferment into 

i. Erythro-dextrin, (C 12 H 20 O 10 ) 9 (giving red with iodine) + 

Maltose (C 12 H 22 O n ). 
then into 2. Erythro-dextrin (C 12 H 20 O 10 ) 8 (giving yellow with iodine) 

+ Maltose 2(C 12 H 22 O U ). 

next into 3. Achroo-dextrin (C 12 H 20 O 10 ) 7 + Maltose 3 (C 12 H 22 O n ). 
And so on; the resultant being: 

Soluble starch (C 12 H 20 O 10 ) 10 + Water 8H 2 O = Maltose 8(C 12 H 22 O n ) + 
Achroo-dextrin (C 12 H 20 O 10 ) 2 . 

Many observers, however, believe that the maltose simultaneously pres- 
ent with erythro-dextrin is not actually split off from the starch molecule in 
the formation of erythro-dextrin, but that it is the product of more advanced 
hydrolysis in other starch molecules. They point out that in such a chemical 
reaction of considerable time duration, it is improbable that all the starch 
molecules are attacked at the same rate or are, at any given moment, equally 
advanced in cleavage. Their theory is that there is a series of more and more 
simple dextrins formed giving rise finally to the disaccharides. 

The presence of sugar in such an experiment is at once discovered by the 
application of Trommer's test, which consists in the addition of a drop or 
two of a solution of copper sulphate, followed by a larger quantity of caustic 
potash. When the liquid is boiled, an orange-red precipitate of copper sub- 
oxide indicates the presence of sugar. 

Influences which Affect the Action of Saliva on Starch. Moderate 
heat, about 37 .8 to 40 C., is most favorable to the rapid cleavage of starch 
by the ptyalin. Cold retards and o C. suspends the action but does not de- 
stroy the ferment. A temperature of 60 C. destroys the ptyalin. 

Removal of the products of salivary digestion as they are formed facili- 
tates the action of the enzyme, as an exeess of these products is detrimental 
to further action. 

The reaction between starch and saliva takes place best in a neutral or 
very faintly alkaline medium and is inhibited by strong alkalies and espe- 
cially by acids even as weak as the acidity of the gastric juice. This last is 
of particular importance since it raises the question as to how long the 
ptyalin may act. 


The action of saliva on starch is not limited to the brief interval during 
which food remains in the mouth, as is now well known, but may continue 
for a time in the stomach. 

Ptyalin is strictly an amylolytic ferment. 

Starch appears to be the only principle of food with the exception of the 
dextrins and glycogen, upon which the saliva acts chemically. The secretion 
has no apparent influence on gum, cellulose, or on fat, and is equally destitute 
of power over albuminous and gelatinous substances. 

The salivary glands of children do not produce functionally active saliva 
till the age of 4 to 6 months, and hence the bad effects of feeding them before 
this age on starchy food, corn-flour, etc., which they are unable to render 
soluble and capable of absorption. 

Salivary Digestion in the Stomach. Laboratory experiments have 
demonstrated that while the addition of even o . 05 per cent, of hydrochloric 
acid will inhibit the action of ptyalin on a solution of starch, if any proteins 
be present in the solution much more acid must be added before the action 
of the ptyalin is stopped. The explanation of the latter fact is that the acid 
unites with the proteins in some chemical combination forming "combined 
acid," which has little effect, comparatively, on ptyalin. This "combined 
acid" gives a red color with litmus, but is distinguished from free acid by 
giving a brownish instead of a bluish color with Congo red. When food enters 
an empty stomach, as happens at the beginning of a meal the acid first com- 
bines with the protein food stuffs and so does not at once affect the ptyalin. 

A still more important fact in its bearing on this subject was recently 
discovered by Cannon, who showed experimentally that starchy foods mixed 
with weak alkali remain alkaline in the stomach for as much as an hour and 
a half. Such foods when swallowed into the stomach are packed away in 
that organ in a mass. The secretion of the acid gastric juice comes in con- 
tact only with the outer surface of the mass, which is not materially disturbed 
by the stomach peristalses. The center of the mass may, therefore, remain 
alkaline until the outer layers are completely eroded away, and the ptyalin 
may continue to act on starch during the whole time. 


When properly masticated, the food is transmitted in successive portions 
to the stomach by the act of deglutition or swallowing. The following account 
of deglutition is based upon the researches of Kronecker and Meltzer, whose 
experiments seem to modify in some details the earlier theory of Magendie: 

The mouth is closed, and the food after thorough mixing with the saliva 
is rolled into a bolus on the dorsum of the tongue. The tip of the tongue is 
pressed upward and forward against the hard palate, thus shutting off the 
anterior part of the mouth cavity. The mylo-hyoid muscles then suddenly 


contract, the bolus of food is put under great pressure and shot backward and 
downward through the pharynx and into the esophagus and, if the food be 
fluid enough, even to the cardiac orifice of the stomach. Coincidently with 
the contraction of the mylo-hyoid muscles, the hyoglossi are thrown into 
action, drawing the tongue backward and downward, not only increasing 
the pressure upon the food, but forcing the epiglottis over the glottis, closing 
the larynx. 

It has been shown by the Roentgen-ray method that the character of the 
food determines somewhat its passage through the esophagus. The dry 
and semisolid foods are seized by the musculation of the esophagus and 
passed down that organ by a peristaltic wave. The longitudinal muscles 
contract, tending to enlarge the diameter of the esophagus in advance of the 
food, while contractions of the circular muscles produce pressure on the 
bolus just behind, thus forcing it along to the cardia. This wave reaching 
the cardiac orifice about six seconds after the commencement of the act of 
deglutition, forces the food into the stomach, the sphincter having previously 
relaxed. The interval of time between the commencement of the act of 
deglutition and the arrival of the more fluid food at the cardiac orifice of the 
stomach may not be more than one-tenth second, though it remains at the 
cardiac orifice without entering the stomach until the first parts of the act of 
swallowing is reinforced by the subsequent contraction of the constrictors of 
the pharynx and the passage of a peristaltic wave down the esophagus. In 
some cases, however, the liquid food is not stopped at the cardiac orifice, 
but is sent through the relaxed sphincter by the original force of the mylo- 
hyoid contraction. 

In man the esophagus was said to contract in three separate segments, 
the first segment lying in the neck and being about six centimeters long, the 
second being the next ten centimeters of the tube, and the third the re- 
maining portion to the stomach. But the later Roentgen-ray observations 
show no break in the continuous passage of the food, though the movement 
of the food is slower in the lower segment of the esophagus. 

The act of swallowing consists, then, of the contraction in sequence of 
the mylo-hyoids, the constrictors of the pharynx, and of the esophagus. The 
computed time of contraction is as follows: 

Contraction of mylo-hyoids and constrictors of the pharynx ... 0.3 

Contraction of the first part of the esophagus 0.9 

Contraction of the second part of the esophagus 1.8 

Contraction of the third part of the esophagus 3.0 


If a second attempt at swallowing be made before the first has been com- 
pleted (that is, before six seconds have elapsed), the remaining portion of the 


first act is inhibited, and the contraction wave reaches the stomach six 
seconds after the commencement of the second act. 

During the act of deglutition the posterior nares are closed through the 
action of the levator palati and tensor palati muscles, which raise the velum; 
the palato-pharyngei, drawing the posterior pillars of the fauces together; 
and the azygos uvulae, which raises the uvula thus forming a complete cur- 
tain. Otherwise the food would pass into the nose, as happens in the case 
of cleft palate. At the same time the larynx is closed by the adductor 
muscles of the vocal cords and the descent of the epiglottis, the larynx being 
drawn upward as a whole through the action of the mylo-hyoid, genio-hyoid, 
thyro-hyoid, and digastric muscles. The presence of the epiglottis is not 
necessary for the completion of the act of deglutition. 

Nervous Mechanism of Deglutition. The sensory nerves engaged 
in the reflex act of deglutition are branches of the fifth cerebral, supplying the 
soft palate; the glosso-pharyngeal, supplying the tongue and pharynx; the 
superior laryngeal branch of the vagus, supplying the epiglottis and the glottis. 
The motor fibers concerned are branches of the fifth, supplying part of the 
digastric and mylo-hyoid muscles and the muscles of mastication; the facial, 
supplying the levator palati; the glosso-pharyngeal, supplying the muscles 
of the pharynx; the vagus, supplying the muscles of the larynx through the 
inferior laryngeal branch; and the hypoglossal, the muscles of the tongue. 
The nerve center by which the muscles are harmonized in their action is 
situated in the medulla oblongata. It cannot be definitely circumscribed, 
but is in the general level of the vagus origin. The movements of the esoph- 
agus are co-ordinated by the complex of sensory and motor fibers of the 
fifth and the ninth to twelfth cranial nerves, which all take some part in this 
complicated reflex. 

Cannon has demonstrated that the smooth muscle of the lower end of 
the esophagus and around the cardiac orifice is maintained in contraction 
by a local reflex mechanism. This prevents regurgitation of the foods. 
The local apparatus is brought into action by the stimulation of sensory cells 
in the mucous membrane of this region of the stomach by the acid of the 
gastric secretion. The reflex is assumed to be a local one taking place through 
the intrinsic nervous mechanism. This acid closure of the cardiac sphincter 
is to be compared with the similar mechanism for the pylorus, see page 356. 


The stomach of man and the carnivora is the dilated portion of the ali- 
mentary canal following the esophagus. The esophagus enters the stomach 
at the cardiac end and the pyloric end of the stomach is continuous with the 
duodenal part of the intestine. It varies in shape and size according to its 
state of distention. It is supplied with nerves from the vagus and from the 
sympathetic and receives a special artery, the gastric artery. 



Structure of the Stomach. The stomach is composed of four coats, 
called, respectively, the external or peritoneal, the muscular, the submucous> 

FIG. 253. The Human Stomach and the Vagus Distribution. R. L., Recurrent 
laryngeal; Ca2, inferior cervical cardiac branch; 0,3, 0,4, cardiac branches of vagus; 
A. P. PI., P. P. PI., anterior and posterior pulmonary plexuses; Oes. PL, esophageal plexus; 
Cast. R. and!,., gastric branches of vagus, right and left; Coe, PL, coeliac plexus; Hep. pi., 
hepatic plexus. 

and the mucous coat. Blood vessels, lymphatics, and nerves are distributed 
in and between them. 



The muscular coat consists of three separate layers of fibers which, accord- 
ing to their several directions, are named the longitudinal, circular, and 
oblique. The longitudinal set are the most superficial and are continuous 
with the longitudinal fibers of the esophagus and spread out in a diverging 

manner over the cardiac end and sides of 
the stomach to the pylorus. The circular 
or transverse coat more or less completely 
encircles all parts of the stomach; this 
coat is thickest at the middle and in the 
pyloric portion of the organ, and forms 
the chief part of the thick ring of the 
pylorus. The next and consequently 
deepest coat, the oblique, is continuous 
with the circular muscular fibers of the 

FIG. 254. 

FIG. 255. 

FIG. 254. From a Vertical Section through the Mucous Membrane of the Cardiac End 
of Stomach. Two peptic glands are shown with a duct common to both, one gland only in 
part, a, Duct with columnar epithelium becoming shorter as the cells are traced down- 
ward; n, neck of gland tubes, with central and parietal or so-called peptic cells; h, fundus 
with curved cecal extremity the parietal cells are not so numerous here. X 400. (Klein 
and Noble Smith.) 

FIG. 255. Cross- sections at Various Levels of Peptic Glands of Stomach. X 400. 
M, Section through gastric pit near surface; M' , section through gastric pit near bottom; 
h, mouth of gland; k, neck; g, body near fundus; the chief cells are shaded lightly; b, parietal 
cells. (Kolliker.) 

esophagus at the cardiac orifice of the stomach. This coat is quite inter- 
rupted and more or less incomplete. The muscular fibers of the stomach 
and intestinal canal are unstriated. 



The mucous membrane of the stomach, which rests upon a layer of loose 
cellular membrane, or submucous tissue, is smooth, soft and velvety. It is 
of a pale pink color during life, and in the contracted state is thrown into 
numerous longitudinal folds or rugae, which disappear when the organ is 
distended. It is composed of a mass of short tubular secreting glands. 

The Gastric Glands. The glands of the mucous membrane of the 
stomach are of two varieties, Cardiac and Pyloric. 

FIG. 256. 

FIG. 257. 

FIG. 256. Longitudinal Section of Fundus of Gland from Dog's Stomach, a, 
Lumen of gland; b, intracellular canals in parietal cells; c, cut-off portion of parietal cell; 
d, chief cells; e, intercellular canals leading from lumen of gland to canals in parietal cells. 

FIG. 257. Tubule of Pyloric Gland of Man. Note the thin basal layer of cytoplasm; 
the reticular cell body containing secretion; the subdivision of the latter in some cells into 
proximal and distal masses. Highly magnified. (Bailey.) 

Cardiac glands are found throughout the whole of the cardiac end of the 
stomach. They are arranged in groups of four or five, which are separated 
by a fine connective tissue. Two or three tubes often open into one duct, 
figure 254, which forms about a third of the whole length of the tube and 
opens on the surface. The ducts and the free surface are lined with colum- 
nar epithelium. The body of the gland is composed of granular secreting 
cells, called chief cells or peptic cells. Between these cells and the membrana 
propria of the tubes are large oval or spherical cells, granular in appearance 
with clear oval nuclei; these cells are called parietal cells. They do not 
form a continuous layer, figure 254. Intercellular tubules extending from 



the duct of the gland between the chief cells and connecting with intracellular 
secretory tubules in the parietal cells have been shown by the Golgi silver 
method, by napthol blue, etc., figure 256. 

As the pylorus is approached the gland ducts become longer and the 
tube proper becomes shorter, and occasionally branched at the fundus. 

The Pyloric Glands. These glands have much longer ducts and larger 
mouths than the peptic glands. 

The parietal cells are absent in the pyloric glands. The pyloric glands 
become larger as they approach the duodenum, also more convoluted and 
more deeply situated. They are directly continuous with Brunner's glands 
in the duodenum (Watney). 

FIG. 258. Scheme of Blood Vessels and Lymphatics of Stomach. X 70. a, Mucous 
membrane; &, muscularis mucosae; c, submucosa; d, inner circular muscle layer; e, outer 
longitudinal muscle layer; A, blood vessels; B, structure of coats; C, lymphatics. (Szymo- 
nowicz, after Mall.) 

Blood vessels and Lymphatics. The blood vessels of the stomach first 
break up in the submucous tissue and send branches upward between the 
closely packed glandular tubes, which anastomose around them by a fine 
capillary network with oblong meshes. Contiguous with this deeper plexus, 
or prolonged upward from it, so to speak, is a more superficial network of 
larger capillaries, which branch densely around the orifices of the tubes and 
form the framework on which are molded the small elevated ridges of mucous 


membrane. From this superficial network the veins chiefly take their origin, 
pass down between the tubes, with no very free connection with the deeper 
intertubular capillary plexus, and open finally into the venous network in 
the submucous tissue. 

The lymphatic vessels surround the gland tubes with a network. 
Toward the fundus of the peptic glands are masses of lymphoid tissue 
which may appear as distinct follicles, somewhat like the solitary glands 
of the small intestine. 

Microscopic Changes in the Gastric Glands During Secretion. 
Langley has made a study of the histological changes in the glandular tissues 
in the fresh state. He finds that during fasting or when the glands are at rest 
the chief cells are granular throughout, being crowded with large highly re- 
fractive granules. During activity these granules gradually disappear pro- 
gressively from the base toward the border of the cell on the lumen of the tube. 
They no doubt represent the zymogen substances from which the first dis- 
charge of enzyme is derived during the activity of secretion. The parietal 
cells are finely granular throughout, though they decrease in size during 
activity, as in fact do the chief cells. Macallum by the use of microchemical 
tests has shown the presence of excess of chlorides in the ducts and in- 
tracellular canals, and in the parietal cells. The pyloric cells do not undergo 
such marked changes, and the mucous cells of the more superficial layers 
of the mucosa cannot be said to show any special changes at the time of 
digestional activity of the other layers. During periods of rest the gastric 
cells increase in size and again become charged with granules as before. 

The Act of Secretion of Gastric Juice. The gastric glands un- 
dergo periods of rest and activity. The active secretion of normal gastric 
juice takes place when food is introduced into the mouth, or in fact the 
mere sight of appetizing food is followed by an abundant secretion of gastric 
juice, as shown by Bidder and Schmidt on the dog with a gastric fistula. Such 
observations strongly indicate that the act is a nervous phenomenon, at least 
under nervous control. 

Quite recently Pavlov has proved that secretory fibers are carried to 
the gastric glands in the vagus trunk. His experiment consisted in estab- 
lishing a gastric fistula, and some days later in dividing the esophagus 
in the neck in such a manner that any food swallowed would be diverted 
to the exterior through the cut end. A " fictitious meal" could then be given 
to the animal, and the effect upon the stomach noted. As long as the vagi 
were intact, certain foods (meats) caused a flow of gastric juice, though 
none of the food reached the stomach. The secretion of gastric juice con- 
tinued for hours with the production of a large quantity of secretion. When 
the vagi had been cut, no secretion occurred. Moreover, he found that direct 
stimulation of the vagus produced a flow of gastric juice. 

Khigine placed foods in an isolated gastric pouch prepared with care to 

3 66 


maintain the nervous relations intact, and it led to secretion of gastric juice 
in the main part of the stomach. This is undoubtedly a nervous reflex effect. 
Recently observations on a case of stricture of the human esophagus 
which prevented food from reaching the stomach have shown that an 
abundant flow of gastric juice takes place when food is taken into the mouth. 


FIG. 259. Very Diagrammatic Representation of the Nerves of the Alimentary 
Canal. Oe to Ret, the various parts of the alimentary canal from esophagus to rectum; 
L. V, left vagus, ending on front of stomach; rl, recurrent laryngeal nerve, supplying upper 
part of esophagus; R. V, right vagus, joining left vagus in esophageal plexus; as. pi., 
supplying the posterior part of stomach, and continues as R' V to join the solar plexus, here 
represented by a single ganglion, and connected with the inferior mesenteric ganglion, m. 
gl.; a, branches from the solar plexus to stomach and small intestine, and from the mesen- 
teric ganglia to the large intestine; Spl. maj., large splanchnic nerve, arising from the 
thoracic ganglia and rami communicantes; r. c., belonging to dorsal nerves from the 6th 
to the Qth (or loth); Spl. min., small splanchnic nerve similarly from the loth and nth 
dorsal nerves. These both join the solar plexus, and thence make their way to the ali- 
mentary canal; c. r., nerves from the ganglia, etc., belonging to nth and i2th dorsal and 
ist and 2d lumbar nerves, proceeding to the inferior mesenteric ganglia (or plexus), m. gl., 
and thence by the hypogastric nerve, n. hyp., and the hypogastric nerve, n. hyp., and the 
hypogastric plexus, pi. hyp., to the circular muscles of the rectum; /. r., nerves from the 2d 
and 3d sacral nerves, S. 2, S. 3 (nervi erigentes) proceeding by the hypogastric plexus to the 
longitudinal muscles of the rectum. (M. Foster.) 

It seems conclusively established at the present time that the secretion of 
gastric juice is a reflex act controlled by a definite nervous mechanism. This 
reflex can be aroused by the sensory stimuli of taste, smell, and even sight. 
It can also be initiated by stimuli arising in the stomach itself by the effects 
of ingredients of the food or by the products of digestion. Indeed, it has 
been shown that peptone is a very efficient stimulus for this stomach reflex. 

Edkins, however, has recently shown that the contact of certain food 
products with the pyloric end of the stomach, where they are slightly ab- 
sorbed, gives rise to some chemical substance a gastric hormone or secre- 



tagogue which acts as a powerful stimulus to gastric secretion when it is 
introduced into the circulation. Such food substances are dextrins, maltose 
and dextrose, proteoses, and above all meat extract. 

The influence of the higher nerve centers on gastric digestion, as in the 
case of emotions, is too well known to need more than a reference. 




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FIG. 260. Table to show the Secretion of Gastric Juice by the Dog. (Lliffine.) 

Immediately on the introduction of food or other stimulating substance, 
the mucous membrane, which was previously quite pale, becomes slightly 
turgid and reddened with the influx of a larger quantity of blood, and the gas- 
tric glands commence actively to secrete. An acid fluid is poured out in 
minute drops and the secretion may continue for hours. 


The Gastric Juice. The first analysis of gastric juice was made by 
Prout on a small and impure specimen. Beaumont made an elaborate and 
classic series of observations on the gastric secretion of Alexis St. Martin, 
in whom there existed, as the result of a gunshot wound, an opening leading 
directly into the stomach near the upper extremity of the great curvature 
and three inches from the cardiac orifice. The introduction of any mechan- 
ical irritant, such as the bulb of a thermometer, into the stomach through 
this artificial opening excited the secretion of gastric fluid. This was drawn 
off, and was often obtained to the extent of nearly an ounce. 

The chemical composition of human gastric juice has been also investi- 
gated by Schmidt. The fluid in this case also was obtained by means of an 
accidental gastric fistula. The mucous membrane was excited to action by 
the introduction of some hard matter, such as dry peas, and the secretion was 
removed by means of an elastic tube. The fluid obtained was found to be 
acid, limpid, odorless, with a specific gravity of i . 002 to i . oio. It contained 
a few cells and some fine granular matter. The analysis of the fluid obtained 
in this way is given below. Essentially it is a weakly acid fluid containing 
hydrochloric acid and enzymes, of which pepsin and rennin are the chief, 
though lipase and maltase are both present. The gastric juice obtained 
from gastric fistulas of dogs and other animals shows some difference in 


Dogs. Human. 

Water 97 1 - 1 ? 994-4 

Solids 28.82 5.60 

Ferment pepsin * 7 5 3 J 9 

Hydrochloric acid (free) 2.7 0.2 

Calcium, sodium, and potassium chlorides; and 

calcium, magnesium, and iron phosphates 8.57 2.19 

The quantity of gastric juice secreted daily has been variously estimated; 
but the average for a healthy adult may be assumed to range from 2,000 to 
3,000 cubic centimeters in the twenty-four hours. 

The Nature and Origin of the Acid of Gastric Juice. The acidity 
of the fluid is due to free hydrochloric acid, although other acids, e.g., lactic, 
acetic, butyric, are not infrequently to be found therein as products of gastric 
digestion or abnormal fermentation. In healthy gastric juice the amount of 
free hydrochloric acid is usually about 0.2 per cent., but may be as much as 
0.3 per cent. In pathological conditions it may be entirely absent, or may 
amount to 0.5 per cent., or even more. 

Hydrochloric acid is the proper acid of healthy gastric juice, and various 
tests have been used to prove this. The tests depend upon changes produced 


in aniline colors by the action of hydrochloric acid even in minute traces, 
whereas lactic and other organic acids have no such action. An aqueous 
solution of oo-tropeolin, a bright yellow dye, is turned red on the addition of 
a minute trace of hydrochloric acid, and aqueous solutions of methyl violet 
and gentian violet are turned blue under the same circumstances. 

The protein matter in the food combines to some extent with the hydro- 
chloric acid, which then is known as combined acid and does not redden litmus- 
paper. As this combination is immediate, it follows that no free acid is found 
in the gastric contents until the amount secreted is more than enough to satu- 
rate the various albuminous affinities. It is partly for this reason that, as al- 
ready mentioned, salivary digestion may continue in the stomach for some 
time after the commencement of gastric digestion. According to Ehrlich, the 
amount necessary to saturate the affinities of 100 grams of various articles 
of diet is as follows: 

Beef (boiled) 2.0 grams of pure HC1. 

Mutton (boiled) 1.9 grams of pure HC1. 

Veal (boiled) 2.2 grains of pure HC1. 

Pork (boiled) 1.6 grams of pure HC1. 

Ham (boiled) 1.8 grams of pure HC1. 

Sweetbread (boiled) 0.9 gram of pure HC1. 

Wheat bread 0.3 gram of pure HC1. 

Rye bread 0.5 gram of pure HC1. 

Swiss cheese 2.6 grams of pure HC1. 

Milk (100 c.c.) o .32-0 .42 gram of pure HC1. 

The acid of the gastric juice is not found until after the secretion is poured 
out on the surface of the mucous membrane of the stomach. Thus Claude 
Bernard after microscopic examination said that there was no acid in the 
gastric glands, that "the acid of the gastric juice is formed only after the 
secretion of the juice, the glands secreting a liquid which breaks up into an 
acid fluid and another product as yet not definitely determined." Harvey 
and Bensley, from whom the translation just given is quoted, confirm Ber- 
nard's views completely. They find by an exhaustive study and by ingenious 
staining methods for identifying alkalinity and acidity, that the acid of gastric 
juice does not make its appearance until the secretion reaches the open 
mouths of the glands and the surface of the mucosa. They observe that 
in the gland ducts the secretion is viscid, adherent, stainable, and "breaks up 
into round droplets which maintain their individuality for several minutes," 
noting "the red reaction also at the same time slowly changing to the blue 
acid reaction, if the secretion has been stained with cyanamin." "From these 
observations we are obliged to conclude that the secretion formed in the gland 
possesses a relatively high content of solids, and that the bulk of the water 
found in the gastric secretion is added at the level of the glandular foveolae." 
The parietal cells are alkaline in reaction and not acid, as are in fact all the 
tissues of the gland. However, the observation is well established that the 



parietal cells are peculiarly rich in chlorides, and these chlorides enter into 
the composition of the secretion and apparently are the final source of the 
hydrochloric acid formed in the secretion. 

Malay holds that the acid probably results from a combination of common 
salt with monosodic phosphate, NaH 2 PO 4 + NaCl = Na 2 HPO 4 + HC1; 
the disodic phosphate is then reconverted by the action of carbonic acid 
and water, Na 2 HPO 4 + CO 2 + H 2 O = NaH 2 PO 4 + NaHCO 3 . All these 
salts are found in the gastric secretion. However, Harvey and Bensley 
believe that the hydrochloric acid is derived from an organic combination of 
the chlorides in the secretion, the nature of which is not determined. 

The Pepsin. The pepsin of the gastric juice is derived from the ac- 
tivity of the chief cells of the fundic glands. The zymogen, pepsinogen, 
which is its immediate precursor, is in all probability represented by the gran- 
ules of the resting cells. The ferment pepsin does not exist as such in the 
cells, for an extract of peptic glands in o . 2 per cent, soda solution kept at 
40 C. retains for hours its power to digest protein when added to o . 2 per 
cent, hydrochloric acid. If the extract be first treated with acid till it is 
active, then neutralized and kept, it quickly loses its power to digest. The 
enzyme is destroyed by the treatment, but the pro-enzyme is not so injured. 

Digestive Action of Pepsin and Hydrochloric Acid. The chief func- 
tion of gastric juice is to alter the protein food stuffs so that they may be 
readily absorbed. Less important functions are the antiseptic action of 
the hydrochloric acid and the coagulation of milk. The chief digestive 
power of the gastric juice depends on the pepsin and acid contained in it, 
both of which are necessary for the process in the stomach. 

This action on proteins may be shown by adding a little gastric juice 
(natural or artificial) to some flakes of fibrin or to diluted egg albumin, and 
keeping the mixture at a temperature of about 37 . 8 C. (100 F.). It is soon 
found that the fibrin goes into solution and that the albumin cannot be pre- 
cipitated on boiling. If the solution be neutralized with an alkali, a precipi- 
tate of acid metaprotein is thrown down. After a while the acid metaprotein 
disappears, so that no precipitate results on neutralization, and proper 
analysis will show that all the fibrin or albumin has been converted into other 
protein ubstances, viz., proteases and peptones. The process, as in the case 
of salivary digestion, is never complete and the final result is always a mixture 
of peptones with proteoses which cannot be further peptonized. The re- 
lative proportions, of course, depend on the duration of the process. A side 
product is found (as an insoluble residue) in artificial gastric digestion which 
gives practically all the protein reactions and is soluble in dilute alkali, 
though insoluble in water, sodium chloride, or dilute acid. This is known 
as anti-albumid and may be changed into peptone by prolonged digestion; it 
does not occur in physiological gastric digestion. The commonest proteose 
is the one formed from albumin and is known as albumose, or by the more 


general name protease; this name is used in the subsequent descriptions of 
the digestive processes. 

All classes of proteins are digested by gastric juice, leading to the produc- 
tion of proteoses and peptones. The change is indicated best by the charac- 
ters of the new protein formed. Peptones have certain characteristics which 
distinguish them from other proteins. They are diffusible; i.e., they possess 
the property of passing through animal membranes. In their diffusibility 
peptones differ remarkably from egg albumin, and on this diffusibility depends 
one of their chief uses. Egg albumin as such, even in a state of solution, 
would be of little service as food, inasmuch as its diffusibility renders difficult 
its absorption or in the case of insoluble proteins effectually prevents absorp- 
tion into the blood vessels of the digestive canal. When completely changed 
by the action of the gastric juice into peptones, albuminous matters diffuse 
readily, and can be then absorbed. Peptones, however, are not found in 
the blood, even of the vessels immediately concerned in absorption from 
the stomach and intestines. As will be shown, the proteins are broken 
down into their simpler cleavage products ^in the intestine. 

Products at Different Stages of Gastric Digestion. The protein 
is first changed into syntonin, or acid metaprotein, by the combined action 
of the pepsin and acid. Though the acid alone is capable of accomplishing 
this step, the fact that it does not do so physiologically is proven by the 
great length of time required in laboratory experiments for the change. 
The acid is absolutely essential to the action of pepsin. 

The next change is the conversion of the syntonin into proteoses which, 
according to Neumeister, occurs in two successive stages. The first of these 
stages is the conversion of syntonin into the primary proteoses; i. e., proto- 
proteose and hetero-proteose. The second is the conversion of both proto- 
proteose and hetero-proteose into the secondary proteoses; i.e., deutero- 
proteose. The last change is the conversion of the deutero-proteose into the 
end product peptone. This last change does not occur to any great extent 
and the proteoses always predominate in the digesting mass. The action 
of pepsin is one of hydrolysis and the products are hydrated forms of protein. 
Schematically the changes in the proteins may be represented as follows: 

Acid meta-protein. 

Proto-proteose. Hetero-protecse. 

Deutero-proteose. Deutero-proteose. 

Peptone. Peptone. 


Circumstances Influencing Gastric Digestion. A temperature of 
about 40 C. is most favorable to gastric digestion. The pepsin is destroyed 
by a temperature of 55 (neutral) to 65 C. (acid solution) and its action is 
retarded and suspended by low temperatures. It is inactive in neutral 
or alkaline solution, for an acid medium is necessary. Hydrochloric is the 
best acid for the purpose, but other mineral acids or the organic acids may 
be substituted for the hydrochloric. Excess of peptone delays the action, and 
the removal of the products of digestion facilitates the process. 

Action of Rennin. Milk is curdled by the action of gastric juice, the 
casein being first precipitated, and then dissolved. The curdling is due to a 
special ferment of the gastric juice, rennin, and is not due to the action of the 
free acid alone. The effect of rennin, which is obtained commercially 
from the fourth stomach of the calf, has long been known, as it is used ex- 
tensively to cause precipitation of casein in cheese manufacture. The fer- 
ment rennin is active in a neutral solution as well as in acid. 

The Action of Gastric Lipase. For many years it has been known 
that fats were digested in the stomach, but it has been a more difficult matter 
to definitely prove the source of the lipase, most physiologists holding that 
the lipase is regurgitated from the intestine. In 1880 Cash proved that 
extracts of the gastric mucosa contained an active lipase which experimentally 
caused the dissociation of neutral fats as tested by the increased amount 
of fatty acid. He removed the pancreas and showed that fats were still 
digested. Ogata made the tests in the living stomach of the dog, closing off 
the opening into the intestine. The stomach thus isolated and washed out 
with physiological saline repeatedly caused the appearance of fatty acid 
when olein was introduced and brought into contact with the living gastric 
mucosa. It is evident that the secretion of the gastric glands contains an 
active lipase. 

The well known observation of Pawlow showing that the secretion of 
pepsin is inhibited by an excess of fat in the stomach, when taken in con- 
nection with other facts showing the specific nature of the digestive 
secretions, see figure 268, suggests that lipase secretion may be thus 

Pancreatic Digestion in the Stomach. Boldyroff has recently shown 
that after the ingestion of fats or fatty foods in sufficient amounts, that the 
secretion of gastric juice is inhibited and that the presence of the pancreatic 
and intestinal secretions can be demonstrated in the stomach contents. 

The accuracy of this observation as suggested from the preceding para- 
graph may be held in question to some extent, since the fat enzymes are 
present in the gastric juice itself. But that there may be regurgitation of 
the intestinal juices into the stomach is further supported by numerous 
clinical observations. This regurgitation may, often does, take place in 
great amount in the later stages of gastric digestion, at the time when the 


pyloric valve is least vigorously active. The presence of bile under these 
conditions is usually taken as indicative of this regurgitation. Under 
these conditions, the pancreatic juice is present in amounts sufficient to 
have a considerable proteolytic and fat-splitting action. 

Time Occupied in Gastric Digestion. Under ordinary conditions, 
from three to four hours may be taken as the average time occupied by the 
digestion of a meal in the stomach. But many circumstances will modify 
the rate of gastric digestion. The chief are: The nature of the food taken 
and its quantity (the stomach should be fairly filled, not distended) ; the time 
that has elapsed since the last meal, which should be at least enough for the 
stomach to be quite clear of food; the amount of exercise previous and 
subsequent to a meal (gentle exercise being favorable, overexertion injurious, 
to digestion); the state of 'mind; and the bodily health. 

Summary of Changes in the Food in Gastric Digestion. Briefly 
summarizing the action of gastric juice, the facts appear as follows: i 
Gastric juice has a specific digestive action on protein foods of all kinds, 
converting them into the more soluble proteases and peptones. The action 
is due to an enzyme, pepsin, acting in and with an acid, hydrochloric acid. 
2. The lipase in gastric juice produces a small amount of fat cleavage, tend- 
ing to convert the fats into fatty acids and glycerin in which condition they 
are absorbed. The presence of fat tends to inhibit the gastric digestion of 
proteins. 3. Milk is first coagulated by a special enzyme, rennin, and then 
digested as any other protein. 4. Gastric juice dissolves soluble substances 
like salts, saccharides, etc. 

5. The enzyme, ptyalin, continues the digestion of the carbohydrates in 
the stomach so long as the food remains neutral or alkaline, but they are 
not digested under the influence of any gastric enzymes. However, maltase 
is present in the gastric juice and aids in the last step in carbohydrate hydroly- 
sis. It is significant that outside the body digestion takes place best at the 
temperature of the body, is destroyed by high heat and suspended by cold, 
o C. Putrefaction is prevented by the acid of natural gastric juice. 


Attention has been called to the fact that the stomach is a muscular sac 
capable of holding quite a large mass of food. During a full meal as much 
as one to two liters or more of semi-solid food is packed away in the organ in 
a comparatively short space of time. The gastric juice is secreted by the 
mucous membrane which surrounds the surface of the food mass. The result 
is that the secretion begins to soften and digest the food over its surface, thus 
tending to liquefy and erode away layer after layer of the food mass. The 
picture is made clearer if one remembers that the food mass is retained al- 
most wholly in the fundus of the stomach. The pyloric portion of the stom- 


ach is quite strongly muscular and quite definitely marked off by the strong 
transverse band at its union with the fundus. 

Acid Closure of the Cardiac and Pyloric Orifices. The gastric 
juice is assisted in accomplishing digestion by the movements of the stomach 
itself. When digestion is not going on, the stomach is uniformly contracted, 
its orifices not more firmly than the rest of its walls; but, if examined shortly 
after the introduction of food, it is found closely encircling its contents, and 
its orifices are firmly closed like sphincters. The cardiac orifice, every time 
food is swallowed, opens to admit its passage to the stomach, and immedi- 
ately closes again. This closure of the cardiac orifice is accomplished by a 
local reflex. The stimulus is the acid secretion covering the mucous mem- 
brane in the immediate neighborhood. 

At the taking of food or immediately thereafter the content of the stomach 
begins to pass through the pyloric orifice into the intestine. But the pylorus 
is quickly closed so completely that Little of the contents escape at this 
time. The pylorus is automatically regulated as demonstrated by Cannon. 
The acid gastric content in the duodenum sets up a local reflex that closes 
the pylorus until the bile and pancreatic juice have neutralized the acid. 
When an alkaline reaction is produced the pylorus relaxes and at the next 
peristaltic wave of contraction is opened again. Indeed it is claimed that in 
the human the pylorus takes more or less part in each peristaltic wave passing 
from the stomach on over the duodenum. 

The Peristalsis of the Stomach. The char- 
acter of stomach movements has been admirably 
determined by recent observers using the X-ray 
method. Thus Cannon, working with cats, has 
shown that in from five to ten minutes after a meal 
slight rings or constrictions occur in the pyloric 
antrum and travel slowly toward the pyloric sphinc- 
ter in the form of a peristaltic wave. Successive 
waves begin a little further back toward the fundus 
each time and follow over the pyloric antrum with 

clock-like regularity, in the cat one wave in ten 
FIG. 261. Diagram to . . 

show the movement of food seconds, which requires in each case about twenty 

in the pylorus at times when seconds for its completion. In man they are 
doubtless slower. These peristalses continue dur- 
ing the whole period of digestion for as much as seven or even more hours. 

These peristaltic contractions aid the gastric juice in carrying away the 
softened layers of food by propelling it into the pylorus. There it is thoroughly 
mixed with the gastric juice, forming the chyme. Figure 261 gives an idea of 
the movement of the food in the antrum. The peristaltic contractions carry 
it forward, but if the valve does not open to permit passage to the duodenum, 
then the pressure will force the chyme back through the center toward the 


fundus. After several minutes, i.e., when the secretion of alkaline bile and 
pancreatic juice into the duodenum is well established, the pyloric sphincter 
will relax more often to allow fluid food to pass to the duodenum, but when 
the more solid particles come up against the sphincter it promptly 
contracts and remains so for some time. Toward the completion of digestion 
even solid undigested particles are carried on into the intestine. 

Hunger Contraction. Our 
present knowledge of the charac- 
ter and nervous regulation of the 

peristaltic contractions of the f ]^^ J ''A.M. 

stomach has been recently immeas- 
urably advanced by the work of 
Carlson. His studies have been on 
man, with and without gastric 
fistula, and on dogs. As a result 
there can no longer be doubt that 

the sensation of hunger is attended ( ^ / ] 12 M . 

with characteristic contractions of 
the empty stomach. Carlson's 
studies of the contractions of the 
empty stomach has established a 
number of points in the nervous 

control. For example, the vagus 

, . . a 

nerves have a tonic influence over 

the organ, and their section " leaves 

the empty stomach on the whole 

permanently hypotonic." This 

control does not readily yield to 

the usual reflexes. The splanchnic 

nerves are, on the other hand, in- ( ) ^/ 5P.M. 

hibitory for the stomach. It is 

through this channel that the 

psychic and other reflexes act to FlG> 262. Outlines of the Roentgen-ray 

control the organ. Carlson studied Shadows of the Stomach Content as Digestion 

. , , Progresses. (Cannon.) 
the phenomena in dogs which had 

both the vagi and the splanchnics sectioned. The stomach thus isolated 
manifests the usual hunger peristalses and often "the hunger contractions 
are identical in rate and character with those of the intact stomach in normal 
(strong) tonus." This indicates that "the primary stimulus to these con- 
tractions is not to be sought in the extrinsic nerves." It follows therefore 
that the extrinsic nerves are merely regulative and modifying for the con- 
tractions of the otherwise automatic organ. Of the two mechanisms, the 
vagus is the more vital and least readily disturbed in its control. 



FIG. 263. Horizontal Section of a 
Small Fragment of the Mucous Mem- 
brane, including one entire crypt of 
Lieberkuhn and parts of several others. 

Vomiting. The expulsion of the contents of the stomach in vomiting 
is preceded by a deep inspiration with closure of the glottis, followed im- 
mediately afterward by strong contractions of the muscles of the abdomen, 
diaphragm, and stomach. The diaphragm forms an unyielding surface 
against which the stomach can be pressed. In this way as well as by 

its own contraction the diaphragm is 
fixed, to use a technical phrase. At the 
same time the cardiac sphincter muscle is 
relaxed, and the orifice which it naturally 
guards is actively dilated. The pylorus 
is closed and, the stomach itself also con- 
tracting, the action of the abdominal 
muscles produces strong compression 
which expels the contents of the organ 
through the esophagus, pharynx, and 
mouth. Reversed peristaltic action of the 
esophagus probably increases the effect. 
It has been frequently stated that the 
stomach itself is quite passive during 
vomiting, and that the expulsion of its 

contents is effected solely by the pressure exerted upon it when the capacity 
of the abdomen is diminished by the contraction of the diaphragm. It is 
true that facts are wanting to demonstrate with certainty the contraction 
of the stomach in vomiting; but cases of fistulous opening into the organ 
appear to support the belief that it does take place; and the analogy of the 
case of the stomach with that of the other hollow viscera, as the rectum 
and bladder, may also be cited in confirmation. 

Vomiting is a reflex act. It can be excited by irritation of the lining of 
the stomach, which is perhaps the normal stimulus. It is excited by stimula- 
tion or irritation of other parts of the alimentary tube; i.e., the pharynx, the 
uvula, the intestine, etc. Vomiting may occur from stimulation of sensory 
nerves from many organs, e.g., kidney, testicle, etc., or by impulses arising 
in the organs of special sense, the eye, olfactory membrane, etc. The sensory 
impulses are co-ordinated by a nerve center located in the medulla. The 
center may also be stimulated by impressions from the cerebrum and cere- 
bellum or by changes arising in the center itself, the so-called central vomiting 
occurring in disease of those parts. The efferent impulses are carried by the 
phrenics and other spinal nerves and by the vagus. 


The food that enters the small intestine has already been subjected to two 
digestive enzymes. The ptyalin of the saliva and the pepsin of the gastric 
juice together with the mechanical processes involved have reduced the food 



to a pulpy mass, the chyme. This peptonized/00d contains most of the total 
quantity of food eaten, little having been absorbed, as we shall see later, but 

FIG. 264. FIG. 265. 

FIG. 264. Piece of Small Intestine (previously distended and hardened by alcohol), 
Laid open to Show the Normal Position of the Valvulae Conniventes. 

FIG. 265. Section of the Pancreas of a Dog During Digestion, a, Alveoli lined with 
cells, the outer zone of which is well stained with hematoxylin; d, intermediary duct lined 
with squamous epithelium. X 350. (Klein and Noble Smith.) 

much of the starch has been changed to soluble maltose and dextrose and 
the protein to albumoses and peptones. The discharge from the stomach 
through the pyloric valve to the duo- 
denum has been going on through 
three or four hours on an average for 
each full meal. This stream of food 
passing down the small intestine, 
slowly because of the valvulse con- 
niventes, meets a number of secretions 
which contain enzymes which act on 
each of the three great food principles, 
proteins, fats, and carbohydrates. 
These secretions are the pancreatic 
fluid, the succus entericus, and the 

The Pancreas. The pancreas 
is situated within the curve formed 
by the duodenum, and its main duct 
opens into that part of the small intes- 
tine through a duct common to it and 

to the liver and about two and a half , 

FIG. 266. Section of the Pancreas of 

inches from the pylorus. Armadillo, Showing the Two Kinds of 

The pancreas bears some resem- Gland-structure. (V. D. Harris.) 



blance in structure to the salivary glands. Its capsule and septa, as well as 
the blood vessels and lymphatics, are similarly distributed. It is, however, 
looser, the lobes and lobules being less compactly arranged. 

Heidenhain has observed that the alveolar cells in the pancreas of a fast- 
ing dog consist of two zones, an inner or central zone which is finely granular, 
.and which stains feebly, and a smaller parietal zone of finely striated proto- 

FIG. 267. Duct with Laterals to the Alveoli. Silver method of Golgi (E. Muller). A 
Duct with branches; m, between the cells. B, Laterals more strongly magnified. 

plasm which stains easily. The nucleus is partly in one, partly in the other 
zone. During secretion it is found that the outer zone increases in size, and 
the central granular zone diminishes, as in the case of the salivary glands. 
The pancreatic cell itself becomes smaller from the discharge of the secretion. 
During a period of rest the granular zone again increases in size and the 
outlines of the cells become full and indistinct. The granules, as in the sali- 
vary cells, are the material from which, under certain conditions, the fer- 
ments of the gland are developed, and which are therefore a zymogen. In 
addition to the ordinary alveoli of the pancreas there are distributed irregu- 



larly in the gland other collections of cells of a different character, the islands 
of Langerhans. These cells are considerably smaller, their protoplasm is 
more granular and less easily stained with hematoxylin, and their nuclei are 
small and stain deeply. The collections of cells vary in size and shape. 
The islands of Langerhans' cells are not concerned with the production of 
the pancreatic juice. The special form of nerve terminations, called 
Pacinian corpuscles, are often found in the pancreas. 

The secretion of the pancreas has been obtained for purposes of experi- 
ment from the lower animals and from man in at least one case. A 
pancreatic fistula is established in the dog by opening the abdomen and 
exposing the duct of the gland which is then made to communicate with 
the exterior. In Pawlow's method a circular bit of the intestinal mucous 
membrane around the mouth of the duct in the intestine is brought to 
the surface and stitched into the wound. The secretion is then easily col- 
lected into a vessel suspended under the opening. 

The Pancreatic Juice. Pancreatic juice is colorless, transparent, 
slightly viscid, and alkaline in reaction. It varies in specific gravity from 
i . oio to i . 030, according as it is obtained from a permanent fistula, when it is 
more watery, or from a newly opened duct. The solids vary in a temporary 
fistula from 80 to 100 parts per thousand, and in a permanent one from 16 to 
50 per thousand. It is characterized by having three distinct and important 
enzymes known as trypsin, amylopsin, and steapsin, whose actions are, respect- 
ively, proteolytic, amylolytic, and lipolytic (fat-splitting). Maltase, which 
inverts the disaccharides, is also present, and a rennin is found in the pan- 
creatic juice. 


From a dog. 




ooo . 76 

080 .4 <; 


OQ . 24 

IQ . c c 

Organic substances . . 

QO .44 





Sodium carbonate 

o. t:8 

7 71 

Sodium chloride . 

7 . s e 

2 . <O 

Calcium, magnesium, and sodium phosphates .... 



An extract of pancreas made from the gland which has been removed 
from an animal killed during digestion possesses the active properties of 
pancreatic secretion. It is made by first dehydrating in absolute alcohol 
the gland which has been cut up into small pieces. After the entire removal 


of the alcohol the gland is pulverized and extracted in strong glycerin. 
The amount of the ferment greatly increases if the gland be exposed to the 
air for three or four hours before placing in alcohol; indeed, a glycerin 
extract made from the gland immediately upon the removal from the body 
often appears to contain none of the ferments. The conversion of zymogen 
in the gland into the ferment takes place only after the gland stands a while. 














- (Stead 

FIG. 268. Three Curves Showing the Secretion of Pancreatic Juice upon a Diet (i) 
of 600 cc. of milk; (2) of 250 gm. of bread; (3) of 100 gm. of meat. The divisions along 
the abscissae represent hours after the beginning of the meal; the figures along the ordinates 
represent the quantity of the secretion in cubic centimeters. (Walter.) 

Dilute acid assists or accelerates the conversion, and if a recent pancreas be 
rubbed up with dilute acid before dehydration, a glycerin extract made 
afterward, even though the gland may have been only recently removed from 
the body, is very active. 

Nervous Regulation of the Secretion of the Pancreas. Fibers from 
the vagus and from the splanchnics are distributed to the pancreas. In 
Pawlow's laboratory it has been found that stimulation of these nerves leads 
to the increased secretion of the pancreas. Popielski, in studying the effects 


of dilute hydrochloric acid solution in the duodenum, which resulted in a 
marked increase of pancreatic secretion, explained the phenomenon as a 
local nerve reflex. 

Doubt has been cast on the whole question of nervous control by the 
recent discovery of the fact that acid (o . 4 per cent, hydrochloric acid) in the 
duodenum results in the production of a chemical substance, by the duodenal 
mucous membrane. This substance secretin, is absorbed into the circulation 
and acts specifically on the pancreas to produce increased activity of the pan- 
creatic cells. Acid extracts of the duodenal mucous membrane produce the 
same effects on the pancreas, in fact this is the current method of experiment- 
ally stimulating the flow of pancreatic juice at the present time, the secretion 
being collected from a tube introduced into the duct. 

Under the normal stimulus of food, the flow of pancreatic juice is greatly 
increased. The increase continues to a maximum in from two to three hours, 
after which it gradually decreases through the period of digestion. Pawlow 
has found a certain amount of adaptation, not only of the quantity but of 
the enzyme composition of the pancreatic secretion, to the kind and character 
of the food (in dogs). 

Action of the Enzymes of Pancreatic Juice. The secretion of the 
pancreas accomplishes its digestive action by means of the enzymes given 
above, viz., trypsin, amylopsin, steapsin, and maltase. 

Trypsin. Trypsin is a proteolytic enzyme. Strange to say, it does not 
exist in the fresh pancreatic juice as such, but makes its appearance only 
when there is an admixture with the succus entericus, the secretion of the 
mucous membrane of the intestine. The succus entericus contains an ac- 
tivating enzyme, enterokinase, which converts the inactive and stable trypsin- 
ogen of the pancreatic juice into the active but less stable trypsin. This fact 
is another of the wonderful series of contributions to the exact knowledge 
of the subject of digestion made from Pawlow's laboratories. 

Trypsin, like pepsin-hydrochloric acid, converts proteins into proteoses 
and peptones. The change, however, does not stop here; the hydrolysis 
with trypsin goes much further. While simple amino-acids, with the excep- 
tion of traces of tyrosine, are not found in gastric digestions, these are rapidly 
split off in the tryptic cleavage. Thus in tryptic digestion are formed: tyro- 
sine, leucine, cystine, amino-valerianic acid, asparaginic acid, glutaminic 
acid, histidine, lysine, and arginine. A portion of the protein, however, 
is not completely broken down, the residue consisting of polypeptids 
containing proline and phenyl-alanine combined with small amounts of 
alanine, leucine, aspartic acid, and glutaminic acid. Glycocoll, when pres- 
ent in the protein digested, is also combined in the resistant polypeptids. 
Crystals of leucine and of tyrosine, especially, can be found in tryptic diges- 
tion mixtures. The products formed from protein in tryptic digestion may 
be given in the following graphic scheme: 



Polypeptids Amino-acids 

Combinations of proline, phenyl- Tyrosine, tryptophane, cystine, 

alanine and glycocoll, with rela- alanine, amino-valerianic acid, 

tively small amounts of alanine, leucine, aspartic acid, glutam- 

leucine, asparaginic acid, and inic acid, histidine, lysine, argi- 

glutaminic acid. nine. 

The ferment trypsin acts best in an akaline medium, but will act also 
in a neutral medium, or in the presence of a very small amount of combined 
acid; it will not work in the presence of free acid. It therefore differs from 
pepsin in being able to act without the aid of any other substance than water. 
In the process of tryptic digestion, protein matter does not swell up at first,, 
but seems to be corroded at once. 

Amylopsin. Starch is converted by amylopsin into maltose by hydro- 
lytic action similar to that of ptyalin, ery thro- dextrin and one or more 
achroo-dextrins being the intermediate products. The amylolytic enzyme 
of the pancreatic juice, which cannot be distinguished from ptyalin, is called 
amylopsin. The maltose thus formed is converted to dextrose by the maltase, 
in which form it is ultimately absorbed. 

Pancreatic juice, according to certain observers, possesses the property 
of curdling milk. It contains a special ferment, rennin, for that purpose. 
The ferment is distinct from trypsin, and will act in the presence of an acid 
(W. Roberts). The milk-curdling ferment of the pancreas is, in some pan- 
creatic extracts, said to be quite powerful, insomuch that i cc. of a brine ex- 
tract will coagulate 50 cc. of milk in a minute or two. 

Steapsin orLipase. Oils and fats are emulsified and saponified by the pan- 
creatic secretion. The terms emulsification and saponification may need a 
little explanation. The term emulsification is used to signify an important 
mechanical change in oils or fats, whereby they are made into an emulsion 
or, in other words, are minutely subdivided into small microscopic particles. 
If a drop of an emulsion be looked at under the microscope, an immense 
number of minute rounded particles of oil or fat of varying sizes will be 
seen. The more complete the emulsion the smaller are these particles. In 
milk, which is a splendid example of an emulsion, the fat droplets vary in 
diameter between i and 5^. An emulsion is formed at once if oil, which 
when old is slightly acid from the presence of free fatty acid, is mixed 
with an alkaline solution. 

Saponification signifies a distinct chemical change in the composition 
of oils and fats. An oil or fat being made up chemically of glycerin, a 


triatomic alcohol, and three fatty-acid radicles which may or may not be 
identical, when an alkali (potassium hydrate) is added to it two changes 
take place; first, the oil or fat is split up into glycerin and its fatty acid; second, 
the fatty acids combine with the alkali to form soaps which are chemically 
known as stearate, oleate, or palmitate of potassium according to the particular 
fatty acid or acids involved. Saponification thus means a chemical splitting 
up of oils or fats into new compounds, and emulsification means merely a 
mechanical splitting up into minute particles. The pancreatic juice has 
been for many years credited with the possession of a special ferment, 
which was called by Claude Bernard steapsin, and which is a lipase or 
fat-splitting ferment. This ferment has not been isolated, but its pres- 
ence may be demonstrated by adding portions of the fresh pancreas 
to butter or other fat and maintaining the proper temperature. Its 
action is made manifest by the liberation of butyric acid, which imparts the 
typical odor to rancid butter. 

The older theory was that only a small portion of the fat eaten was thus 
changed into soap, and that the function of the saponified fat was to assist 
in the emulsification of the remaining major part, a process favorably 
influenced by the bile. Although the proper emulsification of fat is indeed 
a preliminary step favoring more effective contact of the fat splitting enzyme, 
lipase, we now know that all the fat is dissociated into fatty acid and glycerin 
before abosrption can occur. When in disease the entrance of the pancreatic 
juice and the bile into the intestine is interfered with, the feces contain an 
excess of fat. 

All recent experiments, however, tend to support the view of Pflliger 
that the entire fat of the food is changed into fatty acids and glycerin; that 
the fatty acids are entirely, or in part, changed to soaps; and that these soaps, 
or mixture of soaps and free fatty acids, are absorbed in solution. The 
chief facts favoring this view are that: (i) The reaction of lipase is sufficiently 
rapid to allow the saponification of a full fatty meal within the ordinary 
period of digestion; (2) histological examination has never shown that fat 
particles can pass into a columnar cell, and droplets have not been found in the 
broad striated border of the cell; (3) the fat globules found in columnar cells 
after a fatty meal grow steadily larger as the period of absorption progresses, 
indicating that they are deposited from solution; (4) the fatty acids are easily 
soluble in bile solutions, and the solubility of the soaps is greatly increased 
by the presence of bile. The fat constituents, according to this theory, are 
recombined in the columnar cells to form neutral fats where their presence 
can be easily demonstrated by methods of staining. 

Conditions which Influence the Action of the Pancreatic Enzymes. 
The various pancreatic enzymes are influenced by heat, by the presence of 
an excess of digestion products, etc., in the same way as ptyalin and pepsin. 
Pancreatic enzymes act in a neutral, but best in an alkaline solution. The 



trypsin, strange to say, is quickly destroyed by the alkaline solution (Bayliss 
and Starling). The pancreatic juice offers the special case of a secretion of 

FIG. 269. FIG. 270. 

FIG. 269. The Liver from Below and Behind. L. S., Spigelian lobe; L. C., caudate 
lobe;!,. Q., quadrate lobe; R.L., right lobe;Z.L., left lobe; g. bl., gall-bladder; v.c.i., inferior 
vena cava; u.f., umbilical fissure; /. d. v., fissure of the ductus venosus; p, portal fissure with 
portal vein, hepatic artery, and bile-duct. (Wesley, from a His model.) 

FiG. 270. Portion of a Lobule of Liver, a, Bile capillaries between liver cells, the 
network in which is well seen; b, blood capillaries. X 350. (Klein and Noble Smith.) 

proenzyme which is stable in alkaline solution until acted on by enterokinase. 
The amount of kinase present will, therefore, markedly influence the 
amount of digestion of protein per unit of time. 

FIG. 271. Hepatic Cells and Bile Capillaries, from the Liver of a Child Three Months 
Old. Both figures represent fragments of a section carried through the periphery of a 
lobule. The red corpuscles of the blood are recognized by their circular contour; vp 
corresponds to an interlobular vein in immediate proximity with which are the epithelial 
cells of the biliary ducts. (E. Hering.) 

The Secretions of the Liver. The liver, the largest gland in the body, 
situated in the abdomen on the right side chiefly, is an extremely vascular 
organ, and receives its supply of blood from two distant sources, viz., from 
the portal vein and from the hepatic artery, while the blood is returned from 
it into the vena cava inferior by the hepatic veins. Its secretion, the bile, 



is conveyed from it by the hepatic duct, either directly into the intestine or 
when digestion is not going on, into the cystic duct, and thence into the gall- 
bladder, where it accumulates until required. The portal vein, hepatic 
artery, and hepatic duct branch together throughout the liver, while the 
hepatic veins and their tributaries run by themselves. The interstices of the 
vessels are filled by the liver cells. 

Structure of the Liver. The liver is made up of small roundish or 
oval portions called lobules, each of which is about ^ of an inch (about 

P x 

FIG. 272. Section of Liver. X 80. P, Portal vein; H, hepatic artery; B, bile-duct. 


i mm.) in diameter, and includes the minute hepatic artery and hepatic 
duct. The hepatic cells, which form the glandular or secreting part of the 
liver, are of spheroidal form, somewhat polygonal from mutual pressure, 
about 25 to 3o// in diameter, and possess one, sometimes two nuclei. The 
cell substance contains a variable amount of glycogen and often some fatty 
globules and possibly some granules of bile pigment. 

The bile capillaries commence between the hepatic cells, and are bounded 
by a delicate membranous wall of their own. They appear to be always 
bounded by hepatic cells on all sides, and are thus separated from the nearest 
blood capillary by at least the breadth of one cell, figures 271 and 272. 


The gall-bladder, g. bl, figure 269, is a pyriform sac attached to the under 
surface of the liver, and supported also by the peritoneum. The larger end, 
or fundus, projects beyond the front margin of the liver, while the smaller 
end contracts into the cystic duct. It is a muscular walled reservoir covered 
with a serous epithelium and lined by mucous membrane. The function 
of the gall-bladder is to retain the bile during the interval of digestion. 

The Bile. The bile is a somewhat viscid fluid, of a yellow, reddish- 
yellow, or green color, a strongly bitter taste, and, when fresh, with a scarcely 
perceptible odor; it has a neutral or slightly alkaline reaction, and its specific 
gravity is about 1.020. Its color and consistency vary much, quite inde- 
pendent of disease; but, as a rule, bile becomes gradually more deeply colored 
and thicker as it advances along its ducts, or when it remains long in the gall- 
bladder where it becomes more viscid and ropy, darker, and more bitter. 
This is on account of its greater degree of concentration, from resorption of 
its water, and also from being mixed with mucus, lipoids, and phosphatid 
proteins secreted by the lining membrane of the gall-bladder. 


Water 859.2 

Solids Bile salts 91.5 

Fat 9.2 

Cholesterol 2.6 

Proteins and coloring matters 29.8 

Salts 7.7 

140. 8 


Bile salts can be obtained as colorless, exceedingly deliquescent crystals, 
soluble in water, alcohol, and alkaline solutions, giving to the watery solution 
the taste and general characters of bile. They consist of sodium salts of gly- 
cocholic and taurocholic acids; the formula of the former being C 26 H 42 NaNO 6 , 
and of the latter C 26 H 44 NaNSO 7 . 

The bile acids are easily decomposed by the action of dilute acids or alkalies 

C 26 H 43 N0 6 + H 2 = C 24 H 40 6 + CH 2 .NH 2 .COOH. 
Glycocholic Acid Cholic Acid Glycocoll 

C 26 H 46 NSO 7 + H 2 O = C 24 H 40 O 5 + CH 2 .NH 2 .CH 2 SO 3 H. 
Taurocholic Acid Cholic Acid Taurine 

Glycocoll is amido-acetic acid, i.e., acetic acid, CH 3 COOH with one of the atoms of H 
replaced by the radical amidogen CH 2 .NH 2 .COOH. Taurine likewise is amino-ethyl- 
sulphonic acid. Accordingly, it has the formula CH 2 NH 2 CH 2 SO 3 H. The proportion of 
these two salts in the bile of different animals varies, e.g., in the ox bile the glycocholate is in 
great excess, whereas the bile of the dog, cat, bear, and other carnivora contains taurocho- 
late alone. In human bile the glycocholate is in excess (4.8 to 1.5). 

The yellow coloring matter of the bile of man and the carnivora is termed 



bilirubin, C 16 H 18 N 2 O 3 , is crystallizable and insoluble in water, and soluble in 
chloroform or carbon disulphide. A green coloring matter, biliverdin, 
C 16 H 18 N 2 O 4 , which always exists in large amount in the bile of herbivora, is 
formed from bilirubin on exposure to the air or by subjecting the bile to any 
other oxidizing agency, as by adding nitric acid. Biliverdin is soluble in 
alcohol, glacial acetic acid, and strong sulphuric acid, but insoluble in water, 
in chloroform, and ether. It is usually amorphous, but may sometimes 
crystallize in green rhombic plates. 

There is a close relationship between the coloring matters of the blood 
and of the bile and, it may be added, between these and that of the urine, 
urobilin, and of the feces, stercobilin. It is probable they are, all of them, 
varieties of the same pigment, or derived from 
the same source. Cholesterol C 27 H 45 OH, 
and lecithin, C 43 H 84 NPO 8 are constant con- 
stituents of bile. Iron is found among the 
salts of the ash. 

The Role of Bile in Intestinal Digestion. 
Though it is not a true digestive fluid, in 
that it has no ferment and digests nothing 
itself, yet it must be regarded as an important 
aid to digestion for the following reasons: (a) 
Bile assists in emulsifying the fats of the food, 
and dissolves the fatty acids thus rendering 
them more capable of absorption. For it has 
appeared in some experiments in which the common bile-duct was tied that, 
although the process of digestion in the stomach was unaffected, chyle 
was no longer well formed. The contents of the lacteals consisted of clear, 
colorless fluid, instead of being opaque and white, as they ordinarily are 
after feeding. It is, however, the combined action of the bile with the 
pancreatic juice to which the emulsification is due rather than to that of the 
bile alone. The bile itself has a very feeble emulsifying power. If the 
theory be accepted that fats are absorbed as fatty acids and soaps, in 
solution, the action of the bile becomes very important because solutions of 
bile salts have the power of dissolving the fatty acids. The moistening of 
the mucous membrane of the intestines with bile, for this very reason, 
facilitates absorption of fatty matters through it. 

(6) The bile, like the gastric fluid, has a certain but not very considerable 
antiseptic power, and may serve to prevent the decomposition of food during 
the time of its sojourn in the intestines. Experiments show that the contents 
of the intestines are much more fetid after the common bile-duct has been 
tied than at other times. Moreover, it is found that the mixture of bile with 
a fermenting fluid stops the process of fermentation. Contact with bile 
also destroys the digestive action of pepsin on protein. 

FIG. 273. Crystalline Scales of 


Bile is also an excretive fluid carrying waste products thrown off by the 
liver. The liver during fetal life is proportionately larger than it is after 
birth, and the secretion of bile is active, although there is no food in the in- 
testinal canal upon which it can exercise any digestive property. At birth, 
the intestinal canal contains concentrated bile, mixed with intestinal secretion 
and this constitutes the mecanium, or feces of the fetus. In the fetus, there- 
fore, the main purpose of the secretion of bile must be directly excretive. 
Probably all the residue of the bile secreted in fetal life is incorporated in 
the meconium, and with it discharged. 

Mode of Secretion and Discharge of Bile. In considering the flow 
of bile into the intestine, two factors are involved. These are the emptying 
of the gall-bladder and an increased secretion by the hepatic cells. 

The secretion oj bile can be studied by tying the common bile-duct of 
a dog and then making a fistulous opening between the skin and the gall- 
bladder; all the bile secreted is then discharged at the surface. In such 
animals it has been found that the secretion of bile is continuous. With 

FIG. 274. Transverse Section through Four Crypts of Lieberkiihn, from the Large 
Intestine of the Pig. They are lined by columnar epithelial cells, the nuclei being placed 
in the outer part of the cells. The divisions between the cells are seen as lines radiating 
from L, the lumen of the crypt; G, epithelial cells, which have become transformed into 
goblet cells. X 350. (Klein and Noble Smith.) 

the great discharge of bile into the intestine that occurs during the third 
hour after a meal, there is an increased secretion of this fluid. This in- 
creased secretion of bile can also be evoked by the introduction of o . 4 per 
cent, hydrochloric acid into the duodenum, and occurs even after the di- 
vision of all connections between the liver and the central nervous system. 
There is evidence that the increased secretion of bile is brought about 
through a mechanism identical with that for the secretion of pancreatic 
juice, and that in each case one and the same substance secretin is formed 
by the action of the cells of the mucous membrane and absorbed into the 
blood stream and excites both the liver and pancreas to increased activity. 
The emptying of the gall-bladder has been investigated on dogs with a 
Pavlov fistula. In this operation, the orifice of the duct, with the mucous 
membrane around it, is cut out of the wall of the intestine and the latter 



again closed. The excised portion with the opening of the bile duct is 
stitched into the abdominal wound. The natural orifice of the duct is thus 
made to open externally. The discharge of bile is found to begin almost im- 
mediately after taking food; it attains its maximum during tbe third hour, 
coincident with the pancreatic flow, and then rapidly diminishes. Dale has 
shown that the muscular fibers of the wall of the gall-bladder are supplied 
by nerves from both the vagus and the sympathetic. The former are motor, 
while the latter convey inhibitory impulses. The contractions of the gall- 
bladder are provoked reflexly on the passage of the acid chyme into the 
intestine. The gall-bladder acts as a reservoir for the bile during the intervals 
when digestion is not in progress. The 
mechanism by which the bile passes into 
the gall-bladder is simple. The orifice 
through which the common bile-duct com- 
municates with the duodenum is narrower 
than the duct, and appears to be closed, 
except when there is sufficient pressure 
behind to force the bile through it. The 
pressure exercised upon the bile secreted 
during the intervals between periods of 
digestion appears insufficient to overcome 
the force of the sphincter by which the orifice 
of the duct is closed; and the bile in the 
common duct traverses the cystic duct and 
so passes into the gall-bladder. It is proba- 
bly aided in this retrograde course by the 
peristaltic action of the ducts. 

The bile is discharged from the gall- 
bladder and enters the duodenum on the 

introduction of food into the small intestine. F ! G - ^.-Longitudinal. Sec- 

lion of Fundus of Crypt of Lieber- 
It is pressed on by the contraction of the kiihn. b, Goblet cell showing 

coats of the gall-bladder and of the com- mitosis; ^epithelial cell; k .cell of 

Paneth; /, leukocyte in epithelium; 
mon bile-duct. m , mitosis in epithelial cell. Sur- 

When the discharge of the bile into the rounding the crypt is seen the 

stroma of the mucous membrane, 
intestine is prevented by an obstruction of x 530. (Kolliker.) 

some kind, as by a gall-stone blocking the 

hepatic duct, it is reabsorbed in great excess into the blood, and, circu- 
lating with it, gives rise to the well-known phenomena of jaundice. This 
is explained by the fact that the pressure of secretion in the ducts, 
although normally very low, not exceeding 15 millimeters of mercury 
in the dog, is still higher than that of the portal veins. If the pressure 
exceeds 15 mm. the secretion continues to be formed, but passes into the 
blood vessels through the lymphatics. 


The Intestinal Secretion, or Succus Entericus. It is impossible to 
isolate the secretion of the glands of Brunner or of the glands of Lieberkiihn, 
but the total secretion of the intestinal mucosa can be secured by isolating a 
loop of intestine by the operation known as the Thiry fistula. A few drops 
of secretion, the succus entericus, can be obtained by this means. Intestinal 
juice is a yellowish alkaline fluid with a specific gravity of i .on and contains 
about 2 . 5 per cent, of solid matters. 

Intestinal juice has only slight digestive action. It contains a weak pro- 
teolytic enzyme and a weak amylolytic enzyme. Maltase is also present. 
But the chief and most profound importance is given to the intestinal juice 
by the discovery of the activating enzyme, enterokinase. This specific 
activating enzyme for the trypsinogen of the pancreatic juice places the in- 
testinal secretion in the rank of necessary secretion for efficient digestion. 
Enterokinase can be prepared by extracting the superficial scrapings of 
the intestinal mucous coat. The duodenal region is richest in enterokinase, 
but the secretion of the lower intestinal lengths also contains the enzyme. 

Extracts of the mucosa of the intestine have been found to contain an- 
other substance which has the specific action of splitting peptones into 
simpler polypeptids and amino-acids. This substance has been called 

There are, therefore, three important new substances in the succus en- 
tericus (or in the extract of the glands), secretin (page 360), erepsin, and 
enterokinase, in addition to the proteolytic and diastatic enzymes. 

Summary of the Digestive Changes in the Small Intestine. The 
thin chyme, which, during the whole period of gastric digestion, is being con- 
stantly squeezed or strained through the pyloric orifice into the duodenum, 
consists of albuminous matter that is breaking down, dissolving and half 
dissolved; of fatty matter that is mechanically separated and melted, but 
not dissolved at all; of starch in various stages of the process of con- 
version into sugar, and as it becomes sugar dissolving in the fluids 
with which it is mixed; and with these are mingled gastric juice and 
fluid that has been swallowed, together with such portions of the food as 
are not digestible. 

The chyme in the duodenum is subjected to the influence of the bile and 
pancreatic juice and also to that of the succus entericus. All these secretions 
have a more or less alkaline reaction, and at once neutralize the acid of the 
gastric chyme. 

The special digestive changes in the small intestine are: (i) The fats are 
changed by the bile and pancreatic juice in two ways: (a) They are 
chemically decomposed by the alkaline secretions, and a soap and glycerin 
are the result. (6) They are emulsified; i.e., their particles are minutely 
subdivided and diffused, so that the mixture assumes the condition of a 
milky fluid or emulsion. (2) The albuminous substances which have been 


partly dissolved in the stomach are subjected chiefly to the action of the 
pancreatic juice. The pepsin is rendered inert by the bile. The pancreatic 
trypsin proceeds with the further conversion of the proteoses into peptones, 
and, with the erepsin, of the peptones into leucin, tyrosin, and the other 
amino-acids. (3) The starchy portions of the food are now acted on briskly 
by the pancreatic juice and the succus entericus, and are changed to maltose 
and dextrose. (4) Salines are usually in a state of solution before they 
reach the intestine. 

Digestive Changes in the Large Intestine. The changes which take 
place in the chyme in the large intestine are probably only the continuation 
of the same changes that occur in the course of the food's passage through 
the upper part of the intestinal canal. No special enzymes have been clearly 
shown for the mucous membrane of the large intestine. The enzymes of the 
small intestine may continue their action here, being hindered only by the 
acid developed from fermentation processes. 

Action of Micro-organisms in the Intestines. Certain changes take 
place in the intestinal contents independent of, or at any rate supplemental 
to, the action of the digestive ferments. These changes are brought about 


" O 




FIG. 276. Types of Micro-organisms, a, Micrococci arranged singly; in twos, 
diplococci if all the micrococci at a were grouped together, they would be called staphylo- 
cocci and in fours, sarcinae; b, micrococci in chains, streptococci; c, and d, bacilli of 
various kinds, one is represented with flagellum; e, various forms of spirilla;/, spores, either 
free or in bacilli. 

by the action of micro-organisms or bacteria. We have indicated elsewhere 
that the digestive ferments are examples of unorganized ferments, so bacteria 
are examples of organized ferments. Organized ferments, of which the yeast 
plant may be taken as a typical example, consist of unicellular vegetable organ- 
isms, which when introduced into a suitable medium grow with remarkable 
rapidity. By their growth they produce new substances from those supplied to 
them as food. Thus, for example, when the yeast cell is introduced intou solu- 
tion of grape-sugar, it grows, and alcohol and carbon dioxide are produced. 
The alcohol and carbon dioxide arise from the formation by the cell of some 
chemical substances which are allied to the unorganized ferments and which 
greatly increase in amount with the multiplication of the original cell. In 


all such fermentative processes organisms analogous to the yeast cell are 
present, and it is not strange that if the ferment cell is introduced into a 
suitable medium it may by its rapid growth convert an unlimited amount of 
one substance into another. Speaking generally, a special variety of cell 
is concerned with each ferment action, thus one variety has to do with 
alcoholic, another with lactic, and another with acetous fermentation. 

A considerable number of species of bacteria exist in the body during life 
chiefly in connection with the mucous membranes, particularly of the digest- 
ive tract. Many forms of bacteria have been isolated from the mouth, a few 
varieties from the stomach, and a very large number from the intestines. It 
is only in the last-named locality that their multiplication has much effect 
from a physiological point of view. The normal (hydrochloric acid) acidity 
of the stomach usually destroys all the micro-organisms taken in with the 
food, but when the amount of this acid is deficient (and sometimes even 
when it is normal) some of the spores may escape. On reaching the small 
intestine these spores begin to develop in its alkaline medium, and may in- 
crease to such an extent as to stop all intestinal digestion; the point where 
this occurs varies from day to day. The large intestine always swarms 
with micro-organisms, though they do not readily pass the ileocecal valve 
into the small intestine. Some species of bacteria found in the intestine are 
anaerobic; i.e., they do not develop in the presence of free oxygen. 

The changes induced in the intestine by the activity of micro-organisms 
are of two kinds, fermentation and putrefaction; the former of these results 
in the breaking-down of carbohydrate matter, and the latter in the disintegra- 
tion of protein matter. The process of fermentation is the less complex 
and probably occurs normally in the small intestine. The lactic acid fermen- 
tation is the most important, though the butyric acid fermentation is next; 
under the influence of these bacteria the carbohydrates are buty rates 
broken down into lactic and butyric acids, and perhaps into acetic acid 
also. Carbonic acid gas may be formed at the same time and cause flatu- 
lence. Cellulose and other insoluble carbohydrates are decomposed, with 
the formation of marsh gas and hydrogen, which escape by the rectum. 

In putrefaction the process is somewhat similar to that in tryptic diges- 
tion, the proteins being broken down into peptones, leucin, tyrosin, and a 
long row of similar substances, including ammonia in relatively large 
amount from the large intestine. Folin and Denis discovered over four 
times as much ammonia nitrogen in the mesenteric vein as in the carotid, 
0.38 to 0.44 milligrams in 100 centimeters of the blood of the vein and 
from 0.03 to 0.08 milligrams in the same amount of arterial blood from the 
carotid. It also results in the production of various gases, such as carbon 
dioxide, sulphureted hydrogen, ammonia, hydrogen, and methane (marsh 
gas), and of a high percentage of the volatile fatty acids, valerianic and 
butyric. Of the aromatic substances the most important are some phenol 
derivatives and indol and skatol, though their toxicity has been greatly 



overestimated. Indol and skatol undergo oxidation in the liver after ab- 
sorption, forming indoxyl and skatoxyl. They are in part carried off in the 
feces, but when the bowel is obstructed they are absorbed and eventually 
appear in the urine, indoxyl and skatoxyl forming, respectively, indoxyl- 
and skatoxyl-sulphuric acids and their salts. Tyrosin is broken down into 
para-oxy-phenol-propionic acid, paracresol, and phenol; para-oxy-phenol- 
acetic acid is also formed. The phenols, after absorption, are in part con- 
jugated with glycuronic acid which is formed by the incomplete oxidation 
of dextrose and are eliminated into the urine. Experiments have been per- 
formed to determine whether or not the intestinal bacteria are necessary to 
normal digestion. The weight of evidence is in favor of the view that they 
are not. 

The Feces. The contents of the large intestine, as they proceed toward 
the rectum, become more and more solid, lose more liquid and nutrient 
parts, and gradually acquire the odor and consistency characteristic of 
feces. After a sojourn of uncertain duration in the sigmoid flexure of the 
colon, or in the rectum, they are finally expelled by the act of opening the 
bowels, or defecation. The average quantity of matter evacuated by the 
human adult in twenty-four hours is about 200 to 250 grams, but the amount 
and character vary exceedingly according to the food eaten. Vegetable foods 
contain much indigestible matter, while meats and meat diets leave very 
little unabsorbed material to be expelled in the feces. 


The amount of water varies considerably, from 68 to 82 per cent, and 
upward. The following table gives about an average composition: 

Water 733 

Solids, comprising: 

a. Insoluble residues of the food, uncooked starch, cellulose, 

woody fibers, cartilage, horny matter, mucin, seldom 
muscular fibers and other proteins, fat, and cholesterin . 

b. Certain substances resulting from decomposition of foods, 

such as indol, skatol, fatty and other acids ; calcium and 
magnesium soaps 

c. Special excretion, excretin, excretoleic acid (Marcet), 

and stercorin (Austin Flint) 

d. Salts chiefly phosphate of magnesium and phosphate [-267 

of calcium, with small quantities of iron, soda, lime, and 

e. Insoluble substances accidentally introduced with the 


f. Mucus, epithelium, altered coloring matter of bile, fatty 

acids, etc 

g. Varying quantities of other constituents of bile and the 





Intestinal Gases. Under ordinary circumstances, the alimentary 
canal contains a considerable quantity of gases. The presence of gas in the 
intestines is so constant and the amount in health so uniform that there can 
be no doubt that its existence is a normal condition. 

The gas contained in the stomach and bowels is from air swallowed with 
either food or saliva, gases developed by the decomposition of foods, or of the 
secretions and excretions thrown into the intestines. The decomposition of 
foods is the chief source. The following table, compiled by Brinton, is a col- 
lection of analyses that have been made and is chiefly valuable as showing the 
kinds of gases present, although the amounts of the gases vary with 
the diet. 


Whence obtained 

Composition by volume 









3 2 




5 1 



Small intestines . . 


Cecum . . 

I 3 



Expelled per anum 


An analysis of the intestinal gases by Ruge in man is as follows: 


Milk diet 

Meat diet 

Vegetable diet 

Carbon dioxide 

o to 1 6 

8 to n 

2 I to 7 A. 

Hydrogen . . 

A-t + O tJJ. 

o i to i 

Carbureted hydrogen 

*to ** DT- 
o . o 

u . y vu ^ 

2 6 to 3 7 

j. . 5 MJ 4 

Ad. to ? < 


26 to 38 

A f to 6j. 

IO to IQ 


The muscular activity of the intestines accomplishes two important func- 
tions; i.e., it thoroughly mixes the digesting food and secretions and it carries 
the content along the tract. Intestinal peristalses have been described for a 
long time. These peristalses begin as contractions of the circular muscles, 
producing ring-like constrictions that are propagated as waves over the intes- 
tine from above downward. Such constrictions carry the intestinal contents 
forward. The longitudinal muscles by their contraction produce pendular 
motion of the intestine. 

A most instructive contribution to the knowledge of intestinal movements 


has been made by Cannon. He fed cats food mixed with 10 to 33 per cent, of 
subnitrate of bismuth, and observed the shadows of the food when subjected 
to the X-rays. A length of food in the intestine was seen to be constricted 
into a series of oval masses, figure 277. Each of these oval masses is quickly 
constricted in the middle, and neighboring halves of adjacent masses flow 
together. After this process is repeated a number of times a peristaltic wave 
of the type previously described sweeps the whole content of the loop down 
the intestinal tract. The segmentations of the intestine are facilitated by 
pressure from within, perhaps stimulated by the direct pressure of the food. 
In general, hollow organs receive their most effective motor stimulus in this 
manner, i.e., by distention. This rule applies in the lengths of the small 

FIG. 277. Diagram Illustrating the Segmentation of the Food in the Small Intestine. 


Peristaltic contractions of the same general type as in the small intestine 
also occur in the large intestine. Cannon has noted a variation here also. 
The ascending and the transverse loops of the colon sometimes exhibit 
rhythmic antiperistalses which keep the content moving against the ilio- 
cecal sphincter for several minutes at a time. In the meantime digesting 
material is being received into the ascending colon through the ilio-cecal 
sphincter, being slowly forced on by the peristalses of the lower loops of the 
small intestine. From time to time strong general peristalses in the colon 
slowly force the food onward. Under ordinary circumstances remnants 
of unabsorbed material in the colon do not pass beyond the pelvic colon, be- 
ing held at this point until the greater portion of the entire colon is moderately 
filled. When sufficient material has accumulated here, it is evacuated by 
strong peristalses combined with compression by the contracting abdominal 

Reverse peristalsis, antiperistalsis, does not commonly occur in the small 
intestine, but large nutrient enemata introduced into the rectum and colon 
may be forced by antiperistaltic waves in the large intestine against the 
ilio-cecal sphincter at a time when it is atonic and relaxed thus allowing 
materials to pass through the ilio-cecal valve into the small intestine. In 
normal healthy individuals this sphincter reacts, according to Hertz, like 
the sphincter of the pylorus effectively closing the tube. 


Influence of the Nervous System on Intestinal Peristalsis. As in 

the case of the esophagus and stomach, the peristaltic movements of the in- 
testines may be directly set up in the muscular fibers by the presence of food 
acting as the stimulus. Few or no movements occur when the intestines are 
empty, vigorous contractions when filled. The intestines are connected 
with the central nervous system both by the vagi and by the splanchnic nerves, 
as well as by other branches of the sympathetic which come to them from the 
celiac and other abdominal plexuses. The relations of these nerves re- 
spectively to the movements of the intestine and the secretions are probably 
the same as in the case of the stomach already considered. 

The vagus carries the motor fibers for the intestine, while the sympathetics 
are inhibitory. Various states of the central nervous system, such as fear, 
anger, etc., inhibit the intestinal movements. The intestine, and stomach, 
too, carries out peristalses when isolated from the central nervous sys- 
tem and indeed from the body, so that the central connections do not originate 
the rhythmic stimulus but are only regulative. The intestinal movements 
are essentially automatic. It has long been known that isolated portions 
of the intestine contract rhythmically and automatically. This has been 
proven for both the longitudinal and circular muscles, and in the absence 
of the mucous membrane. According to Magnus, rhythmic contractions 
do not occur in the muscle if the plexus of Auerbach be removed. He con- 
cludes that the automatic rhythm is inherent in the local nerve ganglia, 
that it is not a reflex since it occurs in the absence of the mucosa, and that 
the contractions of the smooth muscles are directly dependent upon the local 
nerve distribution. Others contend that the contractions are independent, 
depending on the rhythmic property of the muscle itself, but co-ordinated 
by the complex local nervous mechanism. By either conception the nerve 
connections with the central nervous system are regulative and co-ordinative. 

The innervation of the large intestine is also double in character and 
the relations are doubtless the same as in the small intestine. 

Defecation. The emptying of the bowels is essentially an involuntary 
act which has acquired a certain amount of voluntary regulation. The 
act is accomplished wholly reflexly in dogs with isolated lumbar cord, in 
fact has been observed when the lumbar spinal cord was removed. In 
the latter case defecation occurs by automatic peristalsis of the rectum, and 
colon, while in the former reflexes through the lumbar cord carry out the 
act. When the material that has accumulated in the colon descends into 
the rectum, which is normally empty, it initiates the reflex stimulus which 
culminates in opening the bowel, or defecation. Hertz and others have 
taken X-ray photographs of the human immediately before and after open- 
ing the bowels, with a view to a better understanding of what structures 
take part in the process. It is found that the entire colon as far back as the 
ilio-cecal sphincter may be emptied during the act, see figure 2760. 




Normally in man the rectal stimulus gives rise to the consciousness of 
the desire to defecate and to the initiation of efferent nerve impulses that may 
increase the contraction of the external sphincter and inhibit the act tempo- 
rarily. During opening of the bowels however, the voluntary effort leads to 
relaxation of the external sphincter, and the normal peristalsis of the rectum 
is suppported by contractions of the abdominal musculature so as greatly 
to increase the abominal pressure, thus aiding the involuntary reflex which 
controls the relaxation of 

the internal sphincter and EXAMPLE i 

the contractions of the 
colon, and rectum. 

The Time of Passage 
of Food Through the 
Alimentary Canal. It 
is important to under- 
stand the rapidity with 
which food passes along 
the different divisions of 
the alimentary tube. 

The effectiveness of 
digestion, the dangers 
from fermentation and 
putrefaction, and the ills 
that follow the absorption 
of toxic by-products are 
largely dependent upon 
the time element. 

At the beginning of a 
meal the activity of the 
entire alimentary canal is 

low, and one may assume that the various muscular mechanisms are re- 
latively relaxed. When food is swallowed, immediately small portions 
begin to pass through the stomach and pyloric sphincter. However, the 
main portion of the food passes out of the stomach as it undergoes digestion 
and solution during the succeeding 4 or 5 hours. Hertz, who has given us 
the most accurate picture of the elements in this process allows 4^ hours 
for the passage of food along the 22 feet of the small intestine to the iliac 
sphincter. This he has determined by X-ray photographs after a bismuth 
meal. This is a comparatively rapid passage averaging about 2\ cm. per 
minute. The rate is much slower in the large intestine. He allows an 
average speed of 2 hours each for the ascending, transverse, and descending 
colon. In the short lengths of the iliac and pelvic colons an equal or even 
greater time is consumed. Thus he would allow an average of eighteen 

Immediately after 

FIG. 2j6a. The upper pair of figures show the 
bismuth shadows for normal defecation, the lower 
after the use of magnesium sulphate. (From Hertz, 
Cook, and Schlesinger.) 


hours for the first appearance of the food remnants at the end of the pelvic 
colon where it is retained until the bowels are opened. Of course, assuming 
an empty canal ahead of the moving material, the undigested and waste 
products of the food require on an average from eighteen to twenty-two 
hours for the passage of the entire alimentary tract. The earliest possible 
moment at which food remnants can appear in the feces will be when de- 
fecation occurs just after those remnants which passed immediately through 
the stomach have reached the ascending colon, say five hours. On the other 
hand, assuming that a meal is taken on an entirely empty canal, the food 
remnants will not produce the reflex for opening the bowels until they reach 
the pelvic colon. Hence if the bowels are open only once in twenty-four 
hours, it is obvious that the remnants of a meal may not be passed before 
thirty-six to thirty-eight hours. 




1. Reflex Salivary Secretion. Saliva, which is the mixed secretion 
of the salivary and buccal glands, is produced more or less intermittently. 
Examine, taste, or smell appetizing food, for example, an apple, the salivary 
glands begin to discharge secretion which is poured into the mouth more 
rapidly than under ordinary conditions. This increased activity is a reflex 
secretion. It is brought about by the stimulation of sensory structures which 
lead to afferent nerve impulses reacting on nerve centers in the medulla to 
cause secretory nerve impulses to the glands. The stimulating effect of food 
in the mouth causes the most rapid reflex secretion, which may last through 
several minutes or even hours. Especially stimulating substances are, 
beside food, such substances as tartaric acidj lemon juice, ether, alcohol, etc., 
in fact, anything that produces strong local irritation will lead to reflex 

2. The Secretory Nerves of the Salivary Glands of the Dog. The 
nervous mechanism for the salivary glands is well known, and the anato- 
mical relations are such as to make these glands favorable for studying the 
nervous mechanism of glands in general. 

Anesthetize a dog and bind it to a suitable holder. Expose the nerves to 
the submaxillary gland as follows: cut through the skin of the lower jaw 
along the inner border for about 3 inches. Isolate and double ligate the 
jugular vein and any other veins in the field except the ones coming from the 
submaxillary gland. Isolate and cut the digastric muscle, also the mylo- 
hyoid, using pains not to injure the duct of the gland or its arteries. When 
the muscles are laid back', the artery and accompanying sympathetic nerve 
branches, the hypoglossal and the lingual nerves, the submaxillary duct and 
the submaxillary gland, will all be exposed. Isolate and introduce a very 
fine glass cannula into the submaxillary duct tying it firmly in place. A small 
nerve filament branches from the lingual nerve and runs to the hilus of the 
gland, the chorda tympani. Carefully expose the chorda, place a silk liga- 
ture under it for convenience in handling. Also expose the sympathetic 
filaments with the artery. 

Stimulate the chorda tympani with a mild induction current for a few 
1 minutes at a time at intervals, and note that the secretion which is absent or 
forming slowly before stimulation now gathers quickly and leaves the end 
of the cannula in a series of drops. Collect the saliva in a small beaker. One 
can measure the rate of flow by collecting the saliva in a small graduated 
cylinder or, by changing the beaker every ten minutes, making a record of 
the quantity of secretion formed. Stimulate the sympathetic fibers, cutting 
the hypoglossal nerve if necessary, and note that the secretion is very slightly 


increased, but the increase lasts for only a few minutes. If the sympathetic 
fibers are stimulated before the chorda, then the sympathetic secretion is 
relatively less than if the order of stimulation is reversed. 

Connect the duct with a mercury manometer and record the secretion 
pressure, compare with arterial blood pressure. It is often greater. Explain. 

During stimulation of the nerves, note the relative flow of blood through 
the organ. During chorda stimulation the flow is increased; during sympa- 
thetic stimulation it is decreased, as these nerves contain vaso-dilator and 
vaso-constrictor fibers, respectively. 

Inject 5 milligrams of pilocarpine. This drug stimulates the secre- 
tory nerve endings and thus causes a copious flow of saliva. 

3. Microscopic Changes in the Gland Cells. Make a histological 
preparation (by any standard method of fixing and staining) of the submaxil- 
lary gland of the cat, a, taken after a period of several hours' fasting when 
the gland cells may be assumed to be at rest; and b, immediately after a period 
of activity (from eating, or activity secured by the stimulation of the chorda 
tympani) and note : a, The cells from the resting gland are relatively larger, 
the nuclei are pushed back against the basement membrane, they have 
sparsely sustaining protoplasm, and the cells are crowded with large gran- 
ules, which in a fortunate preparation fill the entire cell. The outlines of the 
cells are relatively indistinct and the lumen of the gland is small, b, The 
cells of the active gland are relatively small, the nuclei are centrally placed, 
the protoplasm stains more definitely, the granules are usually present but 
limited to the side of the cell next to the lumen, the outlines of the cells are 
distinct, and the lumen is often quite large. 

4. The Chemical Composition of Saliva. Collect several cubic cen- 
timeters of saliva as follows: Wash the mouth thoroughly with water, then 
induce secretion of saliva by chewing a bit of paraffin or a piece of thoroughly 
washed rubber. The inhalation of ether vapor will often facilitate the reflex 
secretion. One should avoid strong acids to induce secretion unless their 
presence is to be taken into consideration afterward. Make the following 

Reaction. A slip of neutral litmus-paper when introduced into freshly 
collected saliva, or for convenience simply held in the mouth during sali- 
vary secretion, shows an alkaline reaction. 

Mucin. To 3 or 4 cc. of saliva add 2 per cent, acetic acid drop by drop 
until distinct acidity is obtained. On stirring the saliva with a glass rod a 
sticky mucin makes its appearance. 

Potassium Sulphocyanide. To 2 cc. of saliva in a test-tube add 2 or 3 
drops of ferric chloride solution, slightly acidulated with hydrochloric acid, 
a reddish-brown coloration indicates the presence of potassium sulpho- 
cyanide. One should run a blank test on distilled water for comparison. 


Chlorides. Add silver nitrate to 2 cc. of saliva after first removing 
the proteins. A white, cloudy precipitate, which disappears on adding 
ammonia and reappears on adding nitric acid, indicates the presence of 

Proteins. Remove the mucin from a sample of saliva, as above, and test 
by the characteristic protein reactions. A faint trace of protein can usually 
be demonstrated. 

5. Digestive Action of Saliva on Starch. Review the tests for starch, 
dextrin, and dextrose, as preparation for an identification of these products 
of salivary digestion. To 10 cc. of i per cent, starch paste in the water-bath 
at 40 C., add 2 cc. of saliva, and mix thoroughly with a glass rod. Immedi- 
ately begin two series of tests: a, for the presence of starch; b, for the presence 
of reducing sugar. The tests for starch can be made by adding to 3 drops 
of solution, on a porcelain plate, an equal quantity of dilute iodine in potas- 
sium iodide solution. Use a glass rod. Make the tests every 2 minutes 
for 20 minutes. The tests for reducing sugar are best made by placing 2 cc. 
of Fehling's solution in each of a series of test-tubes and adding to suc- 
cessive tubes, at intervals of 5 minutes, i cc. portions of the digest from a 
dropping pipet and boiling. If the tests are set away as fast as they are pre- 
pared, a reddish-yellow cuprous oxide will settle out, and the series will give 
a rough comparison as to the quantity of reducing sugar present. 

In the first series the deep blue of the starch reaction quickly changes 
to a reddish-blue, a red, a reddish-brown, until finally no change in color 
other than that produced by the mixture of the iodine occurs, showing that 
the starch has passed the second stage of erythro-dextrin in its disappearance. 
The indication of reducing sugar in the second series shows that this erythro- 
dextrin has been transformed into reducing sugar, and also that the amount 
of sugar is greatly increased during the progress of the test. 

6. The Influence of Temperature on Salivary Digestion. Prepare 
three test-tubes, a, 6, c, containing i cc. each of saliva. Boil a, place b in a 
water-bath at 40 C., and place c in ice water. After c has been cooled down 
to the temperature of the ice-bath, add to each 2 cc. of i per cent, starch solu- 
tion and mix. At intervals of 5 minutes test these three samples for the 
disappearance of starch and appearance of reducing sugar, as in Experi- 
ment 5. No change will take place in a; b will be quickly digested, and the 
digestion in c will be slight or suspended. Upon placing c in a warm bath 
digestion will quickly occur. 

7. Influence of Acids and Alkalies on Salivary Digestion. To 
each of 5 test-tubes, a, b, c, d, e, add 2 cc. saliva and water, or the solutions 
given in the table, so that the saliva will be uniformly diluted. Then add 
quickly i cc. of i per cent, starch paste to each. Run parallel tests for the 

appearance of reducing sugar and disappearance of starch. 




The results obtained in Experiments 5, 6, and 7 show that starch is 
converted into reducing sugar, and furthermore, that the conditions for its 
conversion indicate that the change is accomplished by an amylolytic enzyme 
which in this case is called ptyalin. 


A B 




i. Prepare and 
set in water- 
bath at 40 C. 

2 cc. saliva 
2 cc. water 

2 cc. saliva 
2 cc. 0.5 per 
cent, sodium 

2 cc. saliva 

2 CC. 


2 cc. saliva 
2 cc. 0.4 per 
cent, hydro- 
chloric acid 

2 cc. saliva 
2 cc. strong hy- 
drochloric acid 

2. Then add 

i cc. starch 

i cc. starch 

i cc. starch 

i cc. starch 

i cc. starch 

3. Test for 
starch and 

4. After 10 

5. After 20 

6. After 40 

8. The Action of Ptyalin is Favored by the Removal of the End 
Products. Place 50 cc. of 2 per cent, starch paste in a dialyzing tube or 
paper, suspend in a beaker of running water. Take 50 cc. of the same 
solution in a beaker, to each add 2 cc. of saliva and mix thoroughly. Test 
for the disappearance of starch at intervals of 20 minutes. The starch in 
the dialyzing tube will disappear first because the reducing sugar passes out 
through the dialyzer, while in the beaker it is retained and hinders the further 
action of ptyalin. 


9. The Secretion of Gastric Juice. The conditions which influence 
gastric secretion can be readily observed on the dog with a gastric fistula. 
Take a dog which has had a gastric fistula prepared some weeks before and 
which is in a condition of hunger, place him in a holder with a cup suspended 
to collect the gastric juice, and exhibit before the dog some fresh meat or 
other food which he enjoys, but do not allow him to eat it. After teasing the 



FIG. 278. Operation on the Stomach to Form 
an Isolated Pouch with Nerves Intact. S, 
Isolated sac; V, cavity of stomach; A, A, open- 
ing at the abdominal wall. 

animal for 5 to 10 minutes, an abundant flow of gastric juice will begin. 
Pawlow calls this the psychic secretion. 

If an esophageal fistula has also been performed the dog may be allowed 
to eat the meat, of course swal- 
lowing it out of the esophageal 
fistula back into the plate. In 
this experiment an abundant 
flow of gastric secretion takes 
place and may continue for an 
hour or more. 

If a gastric pouch has been 
performed by Pavlov's method, 
the animal may be allowed to 
eat the food, swallowing it into 
the stomach. In this case the 
reflex secretion just described 
takes place as usual, but is fol- 
lowed after an hour or an hour 
and a half by a second increase 
in the quantity of secretion. 
This second increase has been 
ascribed to the reflexes origi- 
nating in the stomach, possibly from the reflex stimulating action of the 
digestive products themselves. 

10. Composition of Gastric Juice. Test a sample of gastric juice 
obtained from a gastric fistula, as follows: 

Reaction. Gastric juice is strongly acid. Test for free hydrochloric acid 
as follows: Gastric juice turns congo-red to a blue color. Gastric juice plus 
0.5 per cent, alcoholic solution of dimethyl-amido-azobenzol develops a 
cherry-red color, a reaction that is given by free hydrochloric acid. Com- 
bined hydrochloric acids and organic acids do not give the color. Giinz- 
burg's reagent, consisting of 2 per cent, phloroglucin and i per cent, vanillin 
in 80 per cent, alcohol, produces a rose-colored mirror on porcelain in the 
presence of free hydrochloric acid. The test is very delicate. 

The lactic acid sometimes present in the contents of the stomach is 
derived partly from the sarcolactic acid of muscle and partly from lactic-acid 
fermentation of carbohydrates. Lactic acid (C 3 H S O 3 ), if present, gives the 
following test: A solution of 10 cubic centimeters of a 4 per cent, aqueous 
solution of carbolic acid, 20 cubic centimeters of water, and one drop of ferric 
chloride is made; forming a blue-colored mixture. A mere trace of free lactic 
acid added to such a solution causes it to become yellow. Inasmuch as 
mineral acids also discharge the color, the lactic acid should first be removed 
from the gastric contents by shaking with ether and the test tried out with a 
solution of the residue after evaporation of the ether. 


Proteins. The usual protein tests (page 107) can be applied to gastric 
juice and show that it contains small quantities. 

11. Artificial Gastric Juice. The active principle, pepsin, of gastric 
juice can be obtained by extracting the gastric mucous membrane of the 
dog, pig, etc. Scrape off the mucous membrane, grind it to a fine pulp by 
repeatedly running it through a sausage machine or by pounding in a mortar 
with clean sand. The mucous membrane should be allowed to stand for 
three or four hours before extraction, otherwise the zymogen, and not the 
enzyme, will be obtained. Extract a portion of this gastric pulp in water and 
filter. Or extract with glycerin for several weeks and filter. Either of these 
extracts contains the enzyme. A solution of the glycerin extract in o . 2 per 
cent, hydrochloric acid contains all the properties of gastric juice. This 
solution is known as artificial gastric juice. 

Commercial pepsin already prepared can be obtained on the market. 
Artificial gastric juice is made from commercial pepsin by adding 0.5 
grams scale pepsin per hundred cc. of 0.2 per cent, hydrochloric acid, which 
gives a very active preparation. 

12. Digestive Action of Gastric Juice, or Artificial Gastric Juice 
on Proteins. The chief digestive action of gastric juice is on proteins. 
Shreds of fibrin which permit the gastric juice to come in intimate contact 
with all parts of the material form the best protein for testing the action of 
this enzyme. Prepare a series of test-tubes, a, b, c, d, each containing 5 cc. 
of artificial gastric juice. Add to a some shreds of fibrin; to b some boiled 
white of egg; to c some fibers of boiled meat; to d some fibers of raw 
meat; place in a warm bath at 40 C. and examine at intervals of 20 
minutes. Tabulate the results by the plan indicated in Experiment 13, 
noting particularly the rapidity with which the different proteins go into 

13. Condition Affecting the Enzyme Action of Gastric Juice. Pre- 
pare a series of test-tubes containing 5 cc. each of gastric juice, according 
to the table on the next page. Add fibrin threads to each and note the 
changes at intervals of 10 minutes. 

14. The Effect of Bile on Peptic Digestion. The influence of bile 
on the activity of pepsin-hydrochloric acid is demonstrated in the following 
steps: i. Place in a series of test tubes, A, B, C, D, 2 cc. each of 0.5 per 
cent, pepsin hydrochloric acid solution. 2. Add to A 2 cc. of water; B 2 
cc. water, o.i cc. bile solution (5 per cent, dried bile); C 1.5 cc. water, 0.5 
cc. bile solution; D 2 cc. bile solution. 3. Add to each test tube 2 cc. of 
0.4 per cent, hydrochloric acid and shake thoroughly. Drop in each test 
tube 4 fibrin threads, and set in water bath at 40 C. Tabulate the results 
at intervals of 10 minutes. 

15. Cleavage Products of Gastric Digestion. Add 5 to 10 grams 
of fibrin to 500 cc. of artificial gastric juice in a flask and place in a water- 
bath at 40 C. After one hour filter off 100 cc. Exactly neutralize this 



filtrate with i per cent, potassium hydrate. A precipitate makes its appear- 
ance, and can be collected on the filter-paper, washed with distilled water, 
and dissolved in i per cent, hydrochloric acid, acid metaprotein. Test 
for the protein reactions. 







2 cc. pepsin 

2cc. hydro- 

2cc. pepsin 

2cc. pepsin 

2cc. pepsin 

2cc. pepsin- 

solution .5 

chloric acid 




alkali solu- 


per cent, in 

0.4 per cent. 




tion. (0.5 per 


acid solu- 

acid solu- 

acid solu- 



tion, (arti- 

tion in ice 


NaHC0 3 ) 

ficial gas- 



tric juice) 

Then add 

4 fibrin 

4 fibrin 

4 fibrin 

4 fibrin 

4 fibrin 

4 fibrin 








after 10 


after 20 


after 40 


after 60 


After twelve hours or more filter the remaining 400 cc., exactly neutralize 
to remove any traces of acid albumin, and filter. The filtrate contains pro- 
teoses and peptones. Concentrate the filtrate over a water-bath to one- 
fourth its volume, add an equal quantity of saturated ammonium sulphate 
solution, a sticky precipitate of primary proteases separates out. Collect on 
a filter-paper or in a centrifuge, wash with half-saturated ammonium 
sulphate, redissolved in very dilute salt solution, and test for protein 
reactions. The primary proteoses are precipitated by nitric acid. 

To the filtrate from the half-saturated ammonium sulphate add crystals 
of ammonium sulphate until complete saturation with the salt. Deutero- 
albumoses separate out. Collect on a filter-paper, wash, dissolve, and test 
for proteins. The secondary proteoses are not precipitated by nitric acid. 

Finally the filtrate contains peptone. It can be isolated and tested by 
concentrating over the water-bath, adding barium hydrate to slight excess 


to remove the sulphate, filtering, and precipitating the excess of barium by 
exact neutralization with i per cent, sulphuric acid. Test for protein reac- 
tions. Peptone gives a rose color in the biuret reaction. The xanthoproteic 
reaction gives the color change, but not the usual precipitate. Peptone is re- 
dissolved from its alcoholic precipitate without change. It is dialyzable. 

1 6. Action of Rennin. Add a solution of commercial rennin (jun- 
ket powder), or of the extract of gastric mucous membrane of the fourth 
stomach of the calf, to 5 cc. of milk and let stand for a few minutes. Repeat 
the test with artificial gastric juice. Also with neutral gastric juice. In each 
case tne milk will form a jelly-like clot, which is firmer in the test-tube con- 
taining commercial rennin. In the test-tube containing artificial gastric 
juice the milk is first coagulated, then slowly dissolved or digested. This 
clotting is due to the special coagulating enzyme, rennin. 


17. The Secretion of Pancreatic Juice. If a dog containing a pan- 
creatic fistula made by Pavlov's method is available, then try the experi- 
ment of feeding the animal and noting the rate of secretion of pancreatic 
juice through a period of two hours. When the gastric digestion has pro- 
ceeded to the point where the acid chyme may be supposed to have entered 
the duodenum, then a sharp increase in the flow of pancreatic juice takes 
place. This increased activity will last through a period of two or three 
hours or more. It is produced either by nerve reflexes (Pavlov) or by the 
influence of the secretin produced by the intestinal mucous membrane when 
stimulated by acid. 

18. Influence of Secretin on the Rate of Secretion. Make an 
extract of the intestinal mucous membrane from the duodenum, by scrap- 
ing off the membrane, grinding it to a pulp, and extracting it over a water- 
bath in 0,2 per cent, hydrochloric acid, and filtering. 

Anesthetize a large dog, open the abdomen, isolate the pancreatic duct, 
introduce a cannula, and arrange for the collection of pancreatic juice. Intro- 
duce a cannula into the saphenous vein and connect it with a buret containing 
the extract of secretin already prepared. Inject 5-cc. quantities of the 
secretin solution into the vein at intervals of ten minutes. Measure the rate 
of secretion of pancreatic juice by counting the drops per minute or, if the 
secretion is rapid enough, by collecting it at intervals of five or ten minutes 
and measuring it in a graduated pipet. 

This method will often yield enough pancreatic juice in the course of a 
couple of hours to make the pancreatic experiments which follow. Bayless 
and Starling call it secretin juice. 

19. Chemical Characters of Pancreatic Juice. Test the reaction, 
protein, salt, etc., content of the sample of pancreatic juice collected in the 
last experiment. 


20. Artificial Pancreatic Juice. Artificial pancreatic juice can be 
prepared from the pancreas by grinding and macerating and extracting a 
pancreas with water or glycerin, as described for the gastric glands in Experi- 
ment ii above. Commerical preparations of pancreatic enzyme can be 
obtained on the market. A solution of a glycerin extract of pancreatic gland 
or of commercial pancreatin in o . 2 per cent, sodium carbonate is known as 
artificial pancreatic juice. 

21. The Enzymes of Pancreatic Juice. The pancreatic juice con- 
tains enzymes which exert a digestive action on starches, fats, and proteins. 
This fact can be tested as follows: a, to 5 cc. of artificial pancreatic juice 
add 2 cc. of i per cent, starch paste, mix and set in the water-bath at 40 C.; 

b, to i cc. of pancreatic juice (artificial juice is not active), collected in Ex- 
periment 17, add 0.5 cc. of neutral olive oil, and place over a water-bath; 

c, to 5 cc. of artficial pancreatic juice add a few flocks of fibrin. Test the 
digestive action on starch by the iodine test for the disappearance of starch, 
or by the copper-reduction test for the presence of reducing sugar. Test the 
fat by its reaction, noting that the neutral or slightly alkaline solution has 
become acid, also by the fact that an emulsion has been formed. Note that 
the protein has gone into solution. 

The digestive action on starch is due to the enzyme amylopsin, or pan- 
creatic diastase, as it is sometimes called. The fat-splitting effect is due to the 
enzyme lipase, and the solution of the fibrin is accomplished by the proteolytic 
enzyme, trypsin. 

22. Conditions which Influence the Action of the Enzymes of 
Pancreatic Juice. Prepare each of 5 test-tubes, a, b, c, d, e, as shown in 
the table on the next page. Place a, b, c, d in the water-bath at 40 C. , and 
e into an ice-bath. Add to each tube 2 cc. of i per cent, starch paste. Follow 
the digestive changes by the tests previously outlined and tabulate the results. 

Repeat this experiment with a second set of test-tubes containing 4 
threads of fibrin in each. Lipase is not very active in artificial pancreatic 
juice and may be omitted, but if pancreatic juice is available make a third 
set containing fat. 

23. Cleavage Products of Pancreatic Digestion. To 400 cc. of arti- 
ficial pancreatic juice add 25 grams of moist fibrin and place in a water-bath 
at 40 C., add 2 cc. of chloroform or of thymolin alcoholic solution to 
prevent putrefactive changes. After three or four hours filter off 100 cc. 
and place the remainder on the water-bath for one or two days. Test the 
filtrate for alkali ablumin, albumoses, and peptones by the method outlined 
in Experiment 14 above. 

Filter the second portion and concentrate to a syrupy mass on the water- 
bath. Crystals make their appearance. Pour off the fluid, wash the crystals 
with cold water, and examine under the microscope for sheaves of tyrosin. 
The filtrate contains leucin. 



If the digestion had been allowed to proceed without the antiseptic, 
bacteria would have appeared in the solution, and protein cleavage products, 
due to their action, would be found, notably indol, phenols, and volatile 
fatty acids. 







2 cc. neutral 
2 cc. 0.5 per 
cent. Na 2 CO 3 

2 cc. neutral 
2 cc. water 

2 cc. neutral 
2 cc. 0.4 per 
cent. HC1 

2 cc. neutral 
2 cc. water. 

2 cc. neutral 
2 cc. Na 2 CO 3 . 
Keep at o C. 

Then add 

2 cc. of starch 

2 cc. of starch 

2 cc. of starch 

2 cc. of starch 

2 cc. of starch 

Note after 
20 min- 

After 40 

After 60 


24. Bile. Secure bile from the gall-bladder of a pig or dog, or, if 
it is possible, a sample of human bile. Test the reaction which, in fresh 
bile, is neutral. Test for mucin, albumin, and for iron; hydrochloric acid 
and ferrocyanide of potassium give a blue color when iron is present. 

BileSalts. Evaporate 10 c.c. of bile to complete dryness, mix with animal 
charcoal, add 50 c.c. of absolute alcohol, filter; add an excess of ether to the 
nitrate, which gives a white precipitate of bile salts. Crystals will form on 
standing in a well -stoppered flask for a day or two. 

Bile Acids. A drop of syrup of cane-sugar in a test-tube of bile forms a 
deep red-purple color at the line of separation from concentrated sulphuric 
acid. Furfur aldehyde with cholalic acid gives the color. 

Bile Pigments. With i c.c. of bile in a test-tube strong nitroso-nitric 
acid produces a play of colors beginning with green, blue, red, and yellow 
Gmelin's test. 

Bile does not contain digestive enzymes, but the bile wets the mucous 
surface of the intestine and facilitates the solution and absorption of fat and 
fatty acids. 

25. Intestinal Juice. The secretion of the mucous membrane of the 
small intestine has been proven to have a weak digestive action on pro- 
teins and perhaps on starches. It can be obtained from an intestinal fistula. 


Its chief digestive importance consists in the presence of the activating 
enzyme, enterokinase. Enterokinase can be prepared by extracting the 
mucous membrane of the small intestine by the method outlined for making a 
pancreatic extract. 

To two test-tubes containing 2 cc. of artificial pancreatic juice, or pref- 
erably containing secretin pancreatic juice, add 2 threads of fibrin. Keep one 
for the control, to the other add 2 cc. of enterokinase solution. The test- 
tube containing enterokinase will digest more rapidly and more effectively 
than the other. 


26. Normal Peristalsis and the Vagus Control of the Frog Stomach 
and Intestine. Pin a pithed frog supine on a frog board. Expose the 
stomach and isolate the vagus. Attach a lever to the outer curvature of 
the stomach by S-shaped hook and thread, so that the contractions register 
as usual. Anchor the gastric mesentery by pin but avoid blood vessels. 

a. Make a continuous record on a slow drum of the normal peristalsis 
of the stomach for 30 minutes. 

b. Stimulate the vagus nerve for 5 to 10 seconds with weak induction 
shocks, as tested by your tongue. Mark the time of stimulation by a 
signal magnet. Allow a long recovery period after each stimulation. 
Repeat with stronger stimuli. 

c. Compare by direct inspection the general characteristics of gastric 
peristalsis both before and following vagus stimulation. Does stimulation 
induce a single contraction or a rhythm? 

d. Transfer the lever to the duodenum and record its normal con- 
tractions. Then stimulate the vagus to test extrinsic motor nerve 

e. Expose the small intestine of the frog just used and make obser- 
vations by inspection without registration. Lightly pinch the pyloric 
stomach or duodenum with a forceps. Note the time with watch and 
determine the rate of peristalsis. Observe the final swinging movements 
of the cloaca or rectum. Remove the intestine and measure its total 
length. Calculate the rate of propagation per centimeter per second and 
the total time for the wave to pass the length of the intestine. 

27. Gastro-intestinal Movements of the Cat. Use a two kilo cat 
which has been fed ground meat four hours before. Give 10 cc. of a 10 per 
cent, chloral hydrate solution per rectum, or 4 grams of urethane, twenty 
minutes before the experiment. Very little ether is then required for 
narcosis. Open the abdomen along the midline to expose the stomach and 
intestine. Protect the visceral organs by covering with very thin wax paper. 


a. Observe two kinds of intestinal movements, segmenting movements 
of the intestine, and peristaltic movements, i.e., rings of contractions 
moving downward. Compare these movements carefully, noting the 
rate of propagation, the sequence, etc. 

b. Note especially the movements of the stomach. Compare the 
pylorus with the fundus. Where does peristalsis commence in the cat 

c. Insert a stomach tube and fill with warm water until distended, 
record any reactions. 

d. Stimulate the vagus in the neck with interrupted induction shocks 
of moderate intensity. 

e. Cut the splanchnics, then stimulate the vagus again. Explain the 

/. Inject i cc. of a o.i per cent, nicotine solution intravenously, 

g. Inject i cc. of o.i per cent, epinephrin. 

28. Pancreatic and Bile Secretion. Anesthetize and tracheotomize 
a dog and connect with the ether apparatus. Expose the jugular for 
venous injections. Ligate the vagus on the same side and section. 
Open the abdomen along the upper half of the linea alba, 6 or 8 inches. 
Expose the duodenum and insert a cannula into the common bile duct 
at the point where it joins the intestine. The greater pancreatic duct 
along the posterior border of the pancreas enters the intestine below the 
bile duct. Carefully dissect and insert a cannula. Provide all the can- 
nulae with small rubber tubes long enough to extend to the surface through 
the wound. Carefully adjust the parts and close the wound by stitches. 

a. Record the rate of pancreatic and bile secretions by signal key. 

b. Stimulate the peripheral end of the vagus in the neck. Give time 
for recovery from the vascular effects and for the secretion to develop. 

c. Inject 20 to 30 cc. of 0.4 per cent, hydrochloric acid by hypodermic 
needle into the duodenum. The reaction is slow. Allow 15 minutes or 
more and repeat. 

d. Inject 40 cc. of "secretin" solution prepared by extracting the 
macerated mucosa of the duodenum with 0.4 per cent. HC1 and 
neutralizing carefully and filtering. Secretin is in solution in the 
filtrate. Repeat in 20 to 30 minutes (Journal of Physiology, Vol. 28, 
P- 2 35> 1920). Read the topic of chemical control and hormones. 


THE term absorption in its restricted physiological use means the 
process by which the digested foods pass through the walls of the alimentary 
canal and into the circulation. In a more general sense absorption is the 
process by which substances pass from one part of the body to another by 
means other than the blood and lymph vessels. Usually absorption takes 
place from a free surface, such as the mucosa of the alimentary canal, the 
surface of the skin, and from the lungs. 

The alimentary canal is lined throughout with a continuous layer of epi- 
thelial tissue. This layer is only a single cell thick in most of its extent, 
but nevertheless it effectively separates the food inside the canal from the 
lymph in the tissue interspaces on the outside of the mucous membrane. 
These spaces are separated from the blood in the adjacent blood vessels by a 
second continuous layer, the endothelial walls of the capillaries. The food, 
therefore, during its absorption from the alimentary canal must pass through 
two layers of tissue to reach the blood stream. But the submucous lym- 
phatic spaces and vessels furnish channels which may carry substances into 
the blood by way of the thoracic duct. The mucous membrane is, therefore, 
the one strict barrier through which the food must pass in the act of absorption. 

The exact methods by which absorption takes place have long been a 
subject of controversy and of research. But this problem is of such diffi- 
culty that it is yet, in the main, unsolved. Known physical and chemical 
laws are thought to explain the facts of absorption. Some of the phys- 
ical factors concerned in absorption and elimination have already been 
considered in a former chapter, osmosis and diffusion, Chapter IV. A third 
factor, filtration, consists in the passage of a fluid under pressure through a 
membrane. These factors undoubtedly play an important role in the pas- 
sage of solutions through the alimentary mucous membrane and the walls of 
the blood vessels. The part which the physical factors play is probably more 
pronounced in the absorption of water and crystalloids. The nature of the 
fluid within the digestive tract, and the movements of the walls of the stomach 
and intestines by means of which the material to be absorbed is brought 
into intimate contact with the absorbing membrane, are additional factors 
which influence absorption. 

But the mechanical and physical factors do not fully explain the observed 
facts of absorption. It becomes more and more evident that there is an 
unexplained factor bound up in the characteristics of the living protoplasm 
of the epithelial cells themselves. When isotonic blood serum is introduced 



into the intestine the salts and water are at once absorbed, also the albumins, 
but more slowly. In this experiment the osmotic conditions are in balance 
and the pressure is greater on the side of the blood vessels, so that absorption 
takes place with the actual expenditure of energy. The important fact 
here is that the absorption through a living membrane is influenced by the 
membrane in ways that we cannot yet explain. It is this factor which de- 
termines the different rate of absorption and the so-called selective absorp- 
tion in different regions of the alimentary canal. 

As a rule, the current of absorption is from the stomach or intestine into 
the blood; but the reversed action may occur, as, for example, when sulphate 
of magnesium is taken into the alimentary canal. In this case there is a 
rapid discharge of water from the blood vessels into the canal. The rapidity 
with which matters may be absorbed and diffused through the textures of 
the body has been found by experiment. It appears that lithium chloride 
may be diffused into all the vascular textures of the body, and into some 
of the non-vascular, as the cartilage of the hip-joint, as well as into the aque- 
ous humor of the eye, in a quarter of an hour after being given by way of the 
mouth and on an empty stomach. Lithium carbonate, when taken in five- 
or ten-grain doses on an empty stomach, may be detected in the urine in 
five or ten minutes; or, if the stomach be full at the time of taking the dose, 
in twenty minutes. 

Absorption in the Mouth. The epithelial lining of the mouth is 
of the thicker stratified type and the conditions are otherwise unfavorable 
for absorption. Little, if any, absorption normally takes place in the mouth, 
and the same is true for the esophagus. 

Absorption in the Stomach. The mucous and submucous coats of 
the stomach, see figure 258, are well supplied with blood vessels and lym- 
phatics. The mucous membrane is, however, so crowded with the peptic 
glands that the relative amount of absorbing surface is small. It is limited 
to the mucous membrane around the mouths of the glands. 

Recent experiments have shown that though absorption does take place 
in the stomach, it is not as active as was formerly supposed, even in the case 
of water. Von Mering has found that water begins to pass from the stomach 
into the intestine almost as soon as it is swallowed, and that very little of it 
is absorbed from the stomach. Of 500 cc. given by the mouth to a large 
dog with a duodenal fistula, only 5 cc. were absorbed in 25 minutes, the 
rest having passed into the intestine. Peptones, sugars, and salts are ab- 
sorbed in the stomach, but only to a limited extent. Peptones are not ab- 
sorbed in appreciable amount unless present to as much as 5 per cent, or 
more. Examination of the mucous membrane during the stage of active 
digestion has revealed the presence of albumoses. Sugars, like peptones, are 
absorbed by the stomach only to a slight extent in the weaker solutions, 
but are readily absorbed when the more concentrated solutions are intro- 



duced into the stomach, 5 per cent, and over (von Mehring). That fats are 
absorbed in the stomach was clearly indicated by von Kolliker as far back as 
1857, although the fact seems to have been more or less ignored all these 
years. He observed an increase in the amount of fat in the gastric mucosa 
of both young and old animals after feeding. This observation has been 
confirmed under carefully guarded experimental conditions, not only for 
the different experimental laboratory animals, but for snakes and a number of 
fishes. The relative amount of fat absorbed through the gastric mucosa is 
small, however, compared with that absorbed by the intestinal villi. Even 


FIG. 279. Scheme of Blood Vessels and Lymphatics of Human Small Intestine, a, 
Central lacteal of villus; b, lacteal; c, stroma; d, muscularis mucosa^; e, submucosa;/, plexus 
of lymph vessels; g, circular muscle layer; h, plexus of lymph vessels; i, longitudinal 
muscle layer; j, serous coat; k, vein; /, artery; m, base of villus; n, crypt; o, artery of villus; 
p, vein of villus; q, epithelium. (Mall.) 

salts in the stomach are not readily absorbed until the concentration is from 
three to four times that of the blood. This fact is in direct opposition to the 
popular views on the subject. 

While some absorption does take place in the stomach it is evidently not 
of any great importance under normal conditions. The presence of alcohol 
has been shown to increase the amount of absorption, and pepper, mustard, 
and such drugs as produce mild local irritation accomplish the same result. 


Absorption in the Intestines. The products of digestion are all readily 
absorbed in the small intestine, as is abundantly shown by experiments. 
Absorption from the small intestine has been studied in the human subject 
in the case of a patient who had a fistulous opening in the lower part of the 
ileum. For example, 85 per cent, of the protein of a test meal was absorbed 
before the food reached the fistula. The food passes slowly down the length 
of the small intestine, and the digestive changes produce a series of cleavages 

Lymphatics of head and I ~"' : - "'ffittHlBi^fe^:;^ '- *V^afcSl Lymphatics of head and 
neck, right ' HlttyS&OT ' && - xfKS^ neck, left 

' 'nl'QBBtHf^ScfuiK^ 

Right internal jugular vein j S^UHHflK^^S Thoracic duct 

Right subclavian vein .___ ___ ... ,____. 

^m.* ^K** -BKB^I^^BHU* Left subclavian vein 
Lymphatics of right arm 

Thoracic duct 

Receptaculum chyli 


Lymphatics of lower ex- SVV^UHi^BYT^^] I Lymphatics of lower ex- 

tremities EnJKIvVHBHHlf'nU^avHP tremities 

FIG. 280. Diagram of the Principal Groups of Lymphatic Vessels. (From Quain.) 

which have known osmotic and diffusion properties. The question has been 
to determine which of the cleavage products are most favorable for absorp- 
tion and the details of the mechanism. 

The mucous membrane of the small intestine possesses special structures 
for absorption, the villi. Each villus projects as a finger-like process into 
the lumen of the intestine. Its single-layered covering of epithelial cells 
supported by a connective-tissue framework brings a relatively large extent 
of surface into contact with the digesting food, which is thus separated from 
a loop of capillaries and lymphatic radicals. 



The capillaries of the villus are connected with the veins which contribute 
to the portal vein, hence carry blood to the liver. The lacteals of the villus 
contribute to the mesenteric lacteal system, hence the chyle and lymph pass 
through the mesenteric glands and the thoracic duct to the subclavian vein 

FIG. 281. 

FIG. 282. 

FIG. 281. Superficial Lymphatics of the Forearm and Palm of the Hand, ^. 5, Two 
small glands at the bend of the arm; 6, radial lymphatic vessels; 7, ulnar lymphatk vessels; 
8, 8, palmar arch of lymphatics; 9, 9', outer and inner sets of vessels; &, cephalic vein; d, 
radial vein; e, median vein;/, ulnar vein. The lymphatics are represented as lying on the 
deep fascia. (Mascagni.) 

FIG. 282. Lymphatic Vessels of the Head and Neck and the Upper Part of the Trunk. 
(Mascagni.) . The chest and pericardium have been opened on the left side, and the 
left mamma detached and thrown outward over the left arm, so as to expose a great part 
of its deep surface. The principal lymphatic vessels and glands are shown on the side 
of the head and face, and in the neck, axilla, and mediastinum. Between the left internal 
jugular vein and the common carotid artery, the upper ascending part of the thoracic duct 
marked i, and above this, and descending to 2, the arch and last part of the duct. The 
termination of the upper lymphatics of the diaphragm in the mediastinal glands, as well as 
the cardiac and the deep mammary lymphatics, is also shown. 



in the neck. There are thus two routes by which absorbed foods may reach 
the general circulation. These paths can be independently isolated; and a 
study of the composition of their discharge during active absorption con- 
tributes to our knowledge of the course taken by the different absorption 

Absorption of Proteins from the Intestines. Protein is absorbed 
chiefly in the small intestine, though just exactly how cannot at present be 
affirmed. In the preceding chapter the cleavage products of protein diges- 
tion have been discussed. It was shown there that proteoses, peptones, 

FIG. 283. A Small Portion of Medullary Substance from a Mesenteric Gland of the 
Ox. d, d, Trabeculae; a, part of a cord of glandular substances from which all but a few of 
the lymph corpuscles have been washed out to show its supporting meshwork of retiform 
tissue and its capillary blood vessels (which have been injected and are dark in the figure); 
b, b, lymph sinus, of which the retiform tissue is represented only at c, c. X 300. (Kolliker.) 

peptids, and the amino-acids are derived from the proteins as digestion 
products. It has, in the past, been assumed that peptone represents the 
form most freely absorbed. No peptone has, however, been isolated from 
the blood or lymph on the vascular side of the epithelial membrane. The 
present supposition is that the protein cleavage products are taken up by 
the epithelium and synthesized into other and more complex forms before 
being discharged into the blood; or that they are resynthetized into the charac 
teristic tissue proteins after absorption. The digestion cleavages not so 
utilized are desamidized by the liver, and the ammonia so formed subse- 
quently converted into and eliminated as urea. 

In animal foods, such as eggs, meat, etc., it is estimated that about 98 
per cent, of the protein is absorbed; whereas in vegetable foods, where the pro- 


tein is often protected from the action of the digestive enzymes, there may 
be 10 to 15 per cent. loss. Analysis of the total lymph discharged by the 
thoracic duct fails to show any increase of proteins during active digestion, 
from which it is inferred that proteins pass by way of the liver. 

The non-nitrogenous residue is oxidized or temporarily stored as glycogen. 

From 12 to 15 per cent, of the protein remains in the food as it passes the 
ileocecal valve. This amount, less the loss in the feces, is absorbed in the 
large intestine. 

Absorption of Carbohydrates by the Intestines. Carbohydrates 
are broken down to dextrose, levulose, etc., and are absorbed as such. Even 

FIG. 284. Section of the Villus of a Rat Killed during Fat Absorption, ep, Epithelium; 
sir, striated border; c, lymph cells; c', lymph cells in the epithelium; /, central lacteal con- 
taining disintegrating lymph corpuscles. (E. A. Schafer.) 

the soluble cane-sugar is split by the invertase of the intestine into the mono- 
saccharides, dextrose and levulose. Starch is the source of most of the 500 
grams of dextrose absorbed in an average diet per day. During the absorp- 
tion of a carbohydrate meal the percentage of dextrose in the blood of the 
portal vein is increased over the normal, which is o . i to 1.5 per cent. This 
excess of dextrose passes through the liver and is temporarily stored in the 
liver cells as glycogen. In the case of a fistula in the receptaculum chyli. 
the chyle contained less than a half per cent, of the total dextrose absorbed. 

Experiments on the rate of absorption of the different sugars seem to 
indicate that their absorption does not follow known physical laws and that 
we must assume an unknown chemical factor in the living protoplasm. 

Dextroses are absorbed readily by the large intestine. 



FIG. 285. Mucous Membrane 
of Frog's Intestine during Fat Ab- 
sorption, ep, Epithelium; str, 
striated border; C, lymph corpus- 
cles; /, lacteal. (E. A. Schafer.) 

Fermentation processes from bacterial growth produce certain acids from 
the carbohydrates, chiefly in the large intestine. These are readily absorbed. 
Absorption of Fats by the Intestines. Fats reach the absorbing 
epithelium in two forms, as soluble glycerol and soaps and as finely emulsi- 
fied fats. The first two are taken up by the epithelium readily enough, 
but the proof of absorption of emulsified fats is not so clear. It is compara- 
tively easy to demonstrate the presence of microscopic globules of fat in the 
intestinal mucosa both in the epithelial cells themselves and to a less degree 

in the intercellular substance. But it has 
been constantly noticed that there is a clear 
zone along the inner or free borders of the 
cells. Fat drops exist in the adjacent 
digesting mass, and in the deeper parts of 
the cells, but not in this border zone. The 
demonstration of the reversible action of 
lipase, has strengthened Pfliiger's fat dis- 
sociation theory which holds that before 
absorption the emulsified fats too must be 
decomposed. They can then pass through 
the cell border and are resynthesized in 
the cell protoplasm. This is of course 
against the strictly mechanical view, which 

must be abandoned in the presence of the evidence supporting the newer 
conception. The decrease in efficiency of fats as foods when the bile, which 
wets the mucous surface and dissolves the fatty acids, is withheld from the in- 
testine, supports this view. As absorption progresses the size of the fat 
drops in the epithelial cells increases, a fact that is readily explained by sup- 
posing a continued synthesis and accumulation of fat. Pfliiger's view 
of absorption has recently received strong support in the observations of 
Bloor that isomannid esters of fatty acids when fed to animals were 
digested but could not be recovered after absorption. Supposing that 
lipolytic cleavage occurred in this fat during digestion, it would of course 
not be rebuilt in the cells of the epithelium after absorption. On the 
theory that the absorption of fats takes place in the emulsified form, this 
compound should have reappeared in the chyle, but it did not. 

The fat is ultimately discharged into the connective-tissue spaces, passes 
through the lymph channels, the thoracic duct, and into the blood of the sub- 
clavian vein. This is the course taken by the larger percentage of the fat. 
However, during absorption some of the fat enters the capillaries of the villi 
and passes through the liver. The presence of fat drops in the liver cells 
at certain times can be ascribed to storage of this absorbed fat, the liver 
exhibiting not only a glycogenic but a lipogenic function. 

It is said that the more readily emulsified fats, those that melt readily at 


the body temperature, are the more completely absorbed. The efficiency 
of such absorption is as high as 96 to 98 per cent, for the oils, and decreases 
sharply for such fats as the tallows. 

The large intestine is capable of absorbing fats, though not so readily as 
the small intestine. 

Absorption of Minerals and Water in the Intestines. The salts 
common in the foods are most of them readily soluble, dissociate quite com- 
pletely in the dilute solutions, and diffuse and dialyze readily. Of the salts 
of the foods, the sodium and potassium cations and chlorine anion are the 
most readily dissociated and are most diffusible, while the calcium and 
magnesium cations and the sulphate anion are least diffusible. The sub- 
stances pass through the intestinal epithelial cells and the intercellular sub- 
stance; at least salts easily recognized by microchemical means have been 
found in both localities during absorption. It seems probable that the forces 
concerned are largely osmosis and diffusion. 

Yet observers have not been able to show that the rate and character of 
the absorption of even the salines obey the known physical laws. In fact, 
there is evidence that some of the salts, iron for example, are taken up as 
organic compounds (hematogens of Bunge). The activity of the epithelial 
cells is to be taken into account, even in the absorption of salts. 

Water, which we have seen is not absorbed in the stomach, is readily 
absorbed in the small intestine. Perhaps the bulk of water taken into 
the system is absorbed in the upper part of the small intestine. In the large 
intestine, too, it is absorbed with facility and in considerable quantities. 
The content of the bowel is still quite fluid when it enters the ascending colon, 
but the feces are quite firm on discharge from the rectum. There are many 
analogies by which we may suppose a controlling influence of the epithelium 
over the process of water absorption. Among the fishes there are species, 
the salmon for example, in which the blood maintains a relatively constant 
osmotic pressure, and therefore salt content. In the salmon this is about 
the same as that of human blood. The blood is separated in the gills by 
an extremely thin epithelium from the water in which the animals live, yet 
these fishes go with impunity from sea- water, with two and a half times more 
salt than the blood, to fresh water with practically no salt at all. The epi- 
thelium of the gills permits the passage of oxygen, but it does not permit 
the diffusion or dialysis of the salts or the water in either direction. It is 
possible that there is a certain amount of resistance to the passage of water 
through the walls of the stomach, while the intestinal epithelium permits 
water to pass readily. 

The factors active in absorption are under searching investigation at the 
present time, so that it is reasonable to hope that the near future will give 
a more exact understanding of this intricate subject. 



The dry corneous stratified epithelium covering the human body pos- 
sesses great resistance to the absorption of most substances. The sebaceous 
secretion keeps the surface slightly oily. Watery solutions do not readily 
wet the surface and therefore do not penetrate. There is some absorption 
of water on prolonged contact with the skin, but the amount is insignificant. 
Medicated baths, especially hot baths, may be accompanied by some slight 
absorption of the substances dissolved in the waters, though it must be con- 
fessed that the primary good effects of such treatment come from other 

On the other hand, oily substances come in more intimate contact with 
the skin and penetrate deeper and more readily. Therefore, lotions con- 
taining medicines are occasionally applied to the skin, and slow but gradual 
absorption occurs. The volatile oils penetrate the skin readily. 

The epithelial lining of the lungs seems peculiarly adapted to the quick 
absorption of gases and volatile substances. This is illustrated by the 
rapidity of adjustment of the body to variations in pressure in the inert 
nitrogen of the air in caisson work and in aviation. The volatile anes- 
thetics, ether and chloroform, penetrate the pulmonary epithelium with 
greatest facility. The same is true for other volatile substances. There is 
increasing evidence that most substances soluble in water