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WORKS OF DR. M. H. FISCHER

PUBLISHED BY

JOHN WILEY & SONS.

The Physiology of Alimentation.

Large i2mo, viii + 348 pages, 30 figures, cloth,
$2 00 net.

TRANSLATION.

Physical Chemistry in the Service of Medicine.

Seven Addresses by Dr. Wolfgang Pauli, Privat-
docent in Internal Medicine at the University of
Vienna. Authorized Translation by Dr. Martin
H. Fischer, iamo, ix+156 pages, cloth, $1 25 net

THE

Physiology of Alimentation

DR. MARTIN IT. FISCHER

Profasor of Pathology in the Oakland College of Medicine

FIRST EDITION
FIRST THOUSAND

NEW YORK

JOnN WILEY & SONS

London: CHAPMAN & HALL, Limited

1907

Copyright, 1907

BY

MARTIN H. FISCHER

ROBERT DRUMMOND, PRINTER, NEW YORK.

TO

C. R. F.

PREFACE.

The following pages are intended primarily for those whose
interests lie in physiology as a science contributory to medi-
cine. In no sense do they constitute a complete review of
the physiology of the alimentary tract, but only such an out-
line of the subject as I have been in the habit of presenting to
my students. This volume is intended to be the first of a
series of monographs dealing with various phases of physi-
ology. Some effort has been made to embody a few of the
ideas that modern physiological investigations have brought
with them, but how long even these recent conceptions will
stand cannot be foreseen. My anticipations will be fulfilled
if the volume serves as a weather-vane which indicates for
the time being the direction in which the wind is blowing.

I am indebted to a number of my friends for suggestions.
To two of these I would express my especial appreciation —
to Dr. Charles S. Arnold of the Oakland College of Medi-
cine, and to Miss Marian O. Hooker of the University of
California.

Martin H. Fischer.

Oakland College of Medicine,
January, 1907.

TABLE OF CONTENTS.

CHAPTER I.

The Mechanical Phenonema of Alimentation. Page

1. The General Functions of the Alimentary Tract 1

2. Mastication 2

3. Deglutition 3

4. The Movements of the Stomach 6

5. The Passage of Different Foodstuffs from the Stomach —

The Opening and Closing of the Pyloric Sphincter. . 16

CHAPTER II.

The Mechanical Phenomena of Alimentation — (Continued).

6. The Movements of the Small Intestine 22

7. The Movements of the Large Intestine 29

8. Defalcation 35

9. The Movement of Food through the Alimentary Tract as

a Whole 36

10. The Nervous Control of the Movements of the Alimentary

Tract 41

11. On the Action of Saline Cathartics 46

12. The Fate of Nutrient Enemas 52

CHAPTER III.

The Juices Poured out upon the Food and Their Chemical Con-
stituents.

1. The Saliva 62

2. The Gastric Juice 66

3. The Pancreatic Juice 68

4. The Bile 70

5. The Intestinal Juice 73

v

Vl TABLE OF CONTENTS.

CHAPTER IV.

Ferments and Fermentation. page

1. Organic Ferments . 79

2. Inorganic Ferments. 93

CHAPTER V.

The Action op the Enzymes Found in the Human Alimentary
Tract.

1 . Amylase 99

2. Maltase 104

3. Caseinase 110

CHAPTER VI.

The Action op the Enzymes Found in the Human Alimentary
Tract — (Continued).

4. Acid-proteinase 114

5. Alkali-proteinase 122

CHAPTER VII.

The Action of the Enzymes Found in the Human Alimentary
T ract — (Continued ) .

6. Quantitative Estimation of the Proteinases 129

7. Antiproteinase 133

8. Why the Alimentary Tract Does not Digest Itself 135

9. The Reversible Action of the Proteinases 140

CHAPTER VIII.

The Action op the Enzymes Found in the Human Alimentary
Tract — (Concluded).

10. Protease 146

11. Lipase 149

12. Sucrase 153

13. Lactase 157

14. Arginase 158

CHAPTER IX.

The Bacteria of the Alimentary Tract 160

TABLE OF COX TENTS. vii

CHAPTER X.

The Regulation of Salivary Secretion.. paob

1. Salivary Fist viler . 177

2. The Relation of the Nerves to Salivary Secretion 178

3. The Reflex Secretion of Saliva 182

4. On the Nature of Salivary Secretion- 186

CHAPTER XI.

The Regulation op Gastric Secretion.

1. Gastric Fistulsc 188

2. Effect of Diet on Gastric Secretion 192

3. Relation of the Nervous System to Gastric Secretion . . . 200

4. The Appetite as an Excitant of Gastric Secretion 203

5. Physiological Importance of the Appetite Juice 205

6. Other Excitants of Gastric Secretion 208

7. Gastric Secretin 211

CHAPTER XII.

The Regulation of Pancreatic Secretion.

1. Pancreatic Fistulse 215

2. Effect of Diet on Pancreatic Secretion 216

3. Relation of the Nervous System to Pancreatic Secretion. 222

4. The Normal Excitants of the Pancreas 224

5. Pancreatic Secretin 227

6. Significance of the Physiology of the Gastric and Pan-

creatic Secretions 230

7. On the Adaptation of the Digestive Glands to the Char-

acter of the Food 234

CHAPTER XIII.

The Regulation of the Biliary and the Intestinal Secretions.
The Functions of the Bile.

1. Secretion of the Bile 237

2. Physiological Importance of the Bile 23S

3. Regulation of the Intestinal Secretion 243

4. Enterokinase 246

viii TABLE OF CONTENTS.

CHAPTER XIV.

The Alimentary Tract as an Absorptive System. page

1. The Problem of Absorption 249

2. The Physical Character of the Foodstuffs 251

3. Membranes 254

4. The Forces Active in Absorption 257

CHAPTER XV.

The Alimentary Tract as an Absorptive System — (Continued).

5. The Absorption of Water 262

6. Lipoidal Absorption . 268

7. The Absorption of Salts 274

CHAPTER XVI.

The Alimentary Tract as an Absorptive System — (Continued).

8. The Absorption of Carbohydrates 282

9. The Absorption of Fats 287

CHAPTER XVEI.

The Alimentary Tract as an Absorptive System — (Concluded).
10. The Absorption of Proteins 299

CHAPTER XVIII.

The Alimentary Tract as an Excretory System.

1. General Considerations, Clinical and Experimental 311

2. The Character of the Alimentary Contents: The Fa3ces.. . 317

PHYSIOLOGY OF ALIMENTATION.

CHAPTER I.
THE MECHANICAL PHENOMENA OF ALIMENTATION.

i. The General Functions of the Alimentary Tract. —
Under the functions of the alimentary tract are included all the
functions of the hollow tube which begins with the mouth
and ends with the anus, together with certain of those of
the glands which pour their secretions into this tube. The
changes which the food undergoes in its passage through
this tube are in part purely mechanical — such for example
as are the consequence of mastication or the movements
of the stomach — in larger part, however, chemical. As an
example of the latter may be mentioned the conversion in
the stomach of albuminous bodies such as egg white into
the chemically less complex peptones. Yet these chemical
changes are frequently associated with physical or physico-
chemical ones which from a physiological standpoint may
at times be quite as important as the chemical changes
themselves.

We can classify the various substances which serve as
food under the general headings of proteins, carbohydrates,
fats, and inorganic substances. Under the first heading
fall, for example, the lean meats, the white of egg, etc.,
while the chief representatives of the carbohydrates are
the starches and sugars which we consume. The fats are

2 PHYSIOLCGY OF ALIMENTATION.

in pari, of animal, in part of vegetable origin. Among the
vegetable fats are the cottonseed and olive oils, while familiar
examples of animal fats are found in butter, cream, and
the fats of fat meat. Water makes up the bulk of the
inorganic material which we consume. Among the other
inorganic constituents of our food are the all-important
salts, which come to us in part as natural components of
our diet, in part as condiments, or as constituents of the
so-called mineral waters.

Representatives of all these classes are found in the or-
dinary mixed diet, and no diet is sufficient for man for any
length of time unless it contains representatives of all these
classes. This mixed diet enters the alimentary tract, some-
times finely divided, sometimes in a state of coarse division.
Some of the constituents of the food may be in suspension
or in solution in water. At times the food is cooked, at
other times uncooked, and in this state is started on its
way through the alimentary tract. The alimentary tract
takes up or absorbs from this heterogeneous mass which
enters the mouth certain constituents of the food either
in the condition in which they are consumed by the indi-
vidual or after they have been acted upon by the secre-
, tions of the alimentary tract. Besides altering the physical
and chemical constitution of the food the alimentary
tract therefore acts as an absorptive system. Interestingly
enough, however, it also acts as an excretory system. All
these various functions, not only the elaboration of the
food by physical and chemical means, but also those of
absorption and excretion, are included under the general
caption, alimentation.

We shall now take up these functions separately, direct-
ing our attention first to the mechanical phenomena which
are associated with the journey of the food through the
alimentary tract.

2. Mastication. — The articulation of the inferior maxillary-
bone with the skull allows of a variety of movements all

MECHANICAL PHENOMENA. 3

of which arc under the control of the will. The lower max-
illary bone may he dropped and raised, may be thrown
forward and drawn backward, and may be moved from
side to side. Ordinary mastication in the human being is
a combination of all these movements. The lower jaw
is lowered and raised in the ordinary biting movements, and
moved from side to side when the food is being chewed.
Combined with both of these may be more or less well-marked
forward and backward movements of the jaw. The food
is kept between the teeth and the act of mastication made
more effective by the simultaneous action of the muscles
of the tongue, cheeks, and lips. The cheeks, and more
especially the tongue, aid also in gathering together the
food in the mouth and forming it into a bolus preparatory
to the act of swallowing.

The muscles concerned in the movements of the lower
jaw are the following. The masseter, temporal, and internal
pterygoid raise the jaw. The digastric is the chief depressor
of the lower maxilla, aided at times by the mylo-hyoid and
genio-hyoid muscles. The jaw is thrown forward by the
simultaneous contraction of the external pterygoids. When
these muscles move singly, side-to-side movements are pro-
duced. The jaw is retracted by contraction of the tem-
poral muscle. The muscles of mastication receive their
nerve supply from the inferior maxillary division of the
fifth cranial nerve with the exception of the genio-hyoid,
which is supplied by the hypoglossal nerve.

3. Deglutition. — It seems to be essential for the proper
performance of the act of deglutition that the mass to be
swallowed be moist. Dry material can either not be swallowed
at all or at best with difficult}'. While certain substances
may therefore be swallowed immediately, it is necessary for
others that they remain in the oral cavity until they have
been thoroughly mixed with saliva, or, in people of improper
dietary habits, until they have been moistened by admixture
with a mouthful of water, tea, or other liquid.

4 PHYSIOLOGY OF ALIMENTATION.

The act of swallowing is usually divided into three parts
corresponding to the anatomical regions through which the
food has to pass, namely, the mouth, the pharynx, and the
oesophagus. But this division, it will be seen, is a purely
arbitrary one and therefore had best not be made. In its
passage through the mouth and the upper portion of the
pharynx the food may be kept under the control of the will.
After the food has come into the grasp of the involuntary
muscle fibres of the oesophagus its movement can no longer
be controlled voluntarily. Under ordinary circumstances,
however, with the exception of the voluntary formation of
the bolus, the entire act is involuntary, and is essentially
reflex in character.

The best experimental observations that we have on the act
of deglutition are those of Kronecker and Meltzer,1 and
those of Cannon and Moser.2 Although the experimental
methods adopted by these investigators are radically different,
their results agree in the main very well.

Preparatory to the act of deglutition the material to be
swallowed is collected into a bolus through the combined
movements of the cheeks, teeth, and tongue. The bolus
rests for a moment on the dorsum of the tongue. According
to Kronecker and Meltzer the chief factor concerned in
forcing food through the pharynx and oesophagus is the quick
and powerful contraction of the mylo-hyoid muscles, aided
by the simultaneous contraction of the hyoglossi muscles.
The contraction of these sets of muscles puts the bolus of
food as it rests on the dorsum of the tongue under high
pressure and shoots it in the direction of the least resistance
through the pharynx and oesophagus. By the contraction
of these muscles the epiglottis is also closed over the tracheal

1 Kronecker and Meltzer: Archiv fur Physiologie, 1880, p. 446;
ibid., 1883, Suppl. BJ., p. 337, 351. Meltzer: Journal of Experi-
mental Medicine, 1897, II, p. 457.

2 Cannon and Moser: American Journal of Fhysiology, 1898, I, p.

435.

MECHANICAL PHENOMENA.

opening. Kronf.ckkr and Meltzkr believe that the food
passes in a spurt from the beginning of the pharynx clear
through the oesophagus to the cardiac orifice of the stomach.
The contraction of the constrictors of the pharynx und the
peristaltic movements of the oesophagus, they believe, follow
this act and serve to remove any fragments which may have
adhered to the oesophagus. This description we shall see
holds only for liquids, and not for more solid foods. They
also believe that, in most individuals at least, the food
does not immediately enter the stomach but is stopped at
the lower end of the oesophagus by a contraction of the
circular muscle fibres of the cardia, and is only slowly forced
into the stomach by the aftercoming peristaltic wave. The
experiments of Cannon and Moser do not support this view.

Cannon and Moser studied the act of deglutition in various
animals, including man, by following the passage of liquids,
solids, and semi-solids mixed with bismuth subnitrate from
the mouth to the stomach by means of the a;-ra3Ts. The
bismuth subnitrate renders the swallowed mass opaque to the
x-rays, and as this method necessitates neither anaesthetics,
operative procedures, nor recording instruments it is freer
from objection than some of the older means employed in the
study of deglutition. According to these authors the move-
ment of food through the oesophagus differs markedly not
only in different animals but also in the same animal with
food of different consistencies. In fowls, for example, the
rate of movement through the oesophagus is always slow, and
no matter what the consistency, it is carried from the pharynx
into the stomach by peristaltic waves. A squirt-like move-
ment when liquids are swallowed is impossible in these ani-
mals, as the parts forming the mouth are too rigid. In order
to get the swallowed mass within the grasp of the oesophageal
musculature the head is raised to aid the weak propulsive
powers of the mouth as largely as possible by gravity.

In the cat also the food is moved through the oesophagus
by peristalsis, but somewhat more rapidly than in the case

6 PHYSIOLOGY OF ALIMENTATION.

of fowls. It requires nine to twelve seconds for a bolus of
solid food to reach the stomach, and a somewhat shorter time
for liquids to make the same journey. The reason for this
difference lies in the fact that liquids move somewhat more
rapidly in the upper portion of the oesophagus than do semi-
solids. In the lower portion of the oesophagus the rate for
both kinds of food is approximately the same. For all kinds
of food the rate of movement in the upper half of the oesoph-
agus is somewhat greater than in the lower half.

In the dog swallowing approximates the same act in the
human being. The total time for the descent of a bolus of
food in this animal is from four to five seconds. In the upper
portion of the oesophagus the movement is always more rapid
than in the lower, and when the swallowed mass is liquid
this rapid movement continues deeper into the oesophagus
than when it is solid or semi-solid. No distinct pause occurs
when the bolus changes from its rapid rate to the slower one.

In man liquids are propelled deep into the oesophagus at a
rate of several feet a second by the sudden and sharp con-
traction of the mylo-hyoid muscles. This confirms the obser-
vations of Kronecker and Meltzer. According to Cannon
and Moser, however, solids and semi-solids are not swallowed
in the same way. From studies on a seven-year-old girl
who was given gelatine capsules filled with bismuth sub-
nitrate, or bread-and-milk mush mixed with the same salt,
they conclude that the movement of food of these con-
sistencies through the oesophagus is always accomplished by.
peristalsis. Nor does the food in its passage through the
oesophagus stop before it enters the stomach, which Kro-
necker and Meltzer believed to be the case. Only the rate
of progressive movement changes from a more rapid one in
the upper oesophagus to a slower one lower down.

4. The Movements of the Stomach. — The movements of
the various portions of the alimentary tract from the oesoph-
agus to the rectum have been the object of research of
many investigators for many years. The pages of this

MECHANICAL PHENOMENA. 7

volume do not allow even an outline <>f the various views
which have been held from time to time. Many of these
we now know to he entirely false, others in part, often in
large part, correct.

Within recent years a number of papers have appeared
on the movements of the gastro-intestinal tract which have
given us a clearer insight into this problem. Foremost
among these newer researches stand the observations of
Cannon in this country and Houx and Bathazard in
Trance. The observations of these men are free from many
of the objections which may be lodged against the older
studies of the subject.

Experiments in mammalian physiology must of necessity
be so often carried on under anaesthetics or the disturbing
influence of operative procedures that when these factors
affect the physiological process which is being investigated
results are obtained which if not wrong are at least con-
fusing. It is to the disturbing influences of the methods
used in the investigation of the movements of the gastro-
intestinal tract by the older observers that some of their
confusing results are to be attributed, and it is but natural
that the introduction of experiments in which all operative
interference, anaesthetics, etc., are shut out should yield
more trustworthy results than our older ones; while they
indicate to us at the same time what is right and what is
wrong in our older conceptions.

Cannon and Roux and Bathazard used the x-ray in
their study of the movements of the alimentary tract. This
does away with the necessity of surgical operations in order
to obtain a view of the intestines, and at the same time
prevents the exposure of the abdominal contents to the cold
of the air, to evaporation, etc., all of them important factors
in modifying the normal activity of the hollow viscera.
In order to render the food visible within the alimentary
tract, bismuth subnitrate was mixed with it. Since this
substance is opaque to the x-rays, the food may readily be

8 PHYSIOLOGY OF ALIMENTATION.

followed in its passage through the alimentary tract by plac-
ing a fluoroscopic screen over the animal.

The only possible sources of error which might have crept
into these observations of Cannon and Roux and Batha-
zard are therefore those connected with tvinp- thp animal dowji

while making nbsprva.t.irm.si fl.nrl t,hp fpprjinp; OT" bismuth ^gub-

nitrate with the food. That the first plays no role in care-
fully conducted experiments is indicated by the fact that
observations carried out on sleeping animals agree per-
fectly with those carried out on waking ones. So far as the
bismuth subnitrate is concerned the objection will be made
that it inhibits the intestinal movements, as it is used for
this purpose in the treatment of diarrhoeas. But care must
be taken in applying what holds for an inflamed gastro-
intestinal tract to a healthy one, in which the action of the
bismuth subnitrate is at its worst but slight.

We shall follow first of all Cannon's 1 description of the
movements of the stomach in the cat.

The form of the active stomach a few minutes after a
meal of 15 grams of milk and bread mixed with 3 to 5 grams
of bismuth subnitrate is shown in Fig. 1. For convenience
in description the stomach may be divided into two parts.
The larger cardiac part lies to the animal's left of the line
through vox. The smaller pyloric part lies to the right of
this line and consists of two subdivisions, the antrum to
the animal's right of a line passing through yz, and a pre-
antral part to the left of this line and extending to the line

Gannon: American Journal of Physiology, 1898, 1, p. 359. See also
Roux and Bathazard: Comptes rendus de la soc. de biologie, 1897,
IV, p. 785; Archives de Physiologie, 1898, X, p. 85. A review of the
older literature on the movements of the stomach may be found in
Cannon's paper. See also Beaumont: Physiology of Digestion, Bur-
lington, 1847, p. 104; Hofmeister and Echtjtz: Archiv f. exper. Patho-
logie und Pharmakologie , 1885, XX, p. 1; Rossbach: Deutsches
Archiv f. klin. Medizin, 1890, XL VI, p. 296; Hirsch: Centralblatt f.
klin. Medizin, 1892, XIII, p. 994.

MECHANICAL PHENOMENA. 9

through vox. The antrum is closed by the pyloric sphincter
at p.

The wall of the stomach consists of three layers of smooth
muscle fibres, an outer longitudinal, a middle circular, and
an inner oblique coat. Smooth muscle is characterized
physiologically by its power of slow rhythmic contraction
and relaxation and its power of prolonged contraction (tonic-
ity). The role that these characteristics play in determining
the normal movements of the stomach can be best appre-

Rife'lu

(Copied from Cannon: American Journal of Physiology, 1898,1, p. 360.)

ciated by a study of the accompanying figures, which indi-
cate the changes that occur in the shape of the stomach
after an ordinary meal (Fig. 2).

Within five minutes after a meal of bread a slight annular
constriction appears near the duodenal end of the antrum
and moves peristaltically towards the pylorus. This is
followed by several other waves of similar character. Two
or three minutes after the first movement is seen, very slight
constrictions appear near the middle of the stomach (the
preantral part) and becoming deeper move slowly toward
the pylorus. As digestion goes on the antrum becomes
somewhat elongated and the constrictions somewhat deeper,
but never until the stomach is nearly empty do they divide
the cavity entirely. The waves recur at intervals of almost
exactly ten seconds and take about thirty-six seconds to
pass from the middle of the stomach to the pylorus. When
one wave is just beginning several others are therefore already

10 PHYSIOLOGY OF ALIMENTATION.

Fig. 2.
(Copied from Cannon: American Journal of Physiology, 1898, 1, p. 370.)

MECHANICAL PHENOMENA.

11

Or ?

Fig. 2 — Continued.

12 PHYSIOLOGY OF ALIMENTATION.

running before it as indicated in Fig. 2 (11.30-1.30). Between
the rings of constriction the stomach is bulged out. Cannon
has calculated the number of waves which pass over the_
ptnmach d.11r^nff «■ sinfrlp digestive period lasting apprpxi-

rnat.ply aftvftn hours an 2fiOD.

The food slowly passes out of the stomach into the duode-
num. The exact manner in which this happens has, however,
been variously described by different authors. Those who
with Hirsch saw the food pass from the stomach into the
duodenum at intervals are probably correct. In cats, Cannon
found that no food appeared in the duodenum until the con-
strictions had been passing over the antrum for ten or fifteen
minutes. When the food did appear it was squirted through
the pylorus for some distance along the intestine. Every
constriction wave does not force food through the pylorus.
Several waves usually pass over the antrum before one is ef-
fective in this particular. At times two or three succeeding
waves may each force food through the pylorus, but usually
it remains closed for some time after it has allowed one con-
striction wave to pass food into the duodenum. The cause
of this opening and closing of the pylorus will be discussed
further on.

When a hard bit of food reaches the pylorus the sphincter
closes tightly and remains closed longer than when the food
is soft. This can be shown experimentally by feeding along
with an ordinary meal pellets of bismuth subnitrate made up
with starch paste. These can be readily recognized as
darker spots in the general shadow cast by the gastric contents
upon the fluoroscopic screen. When such pellets are given
with the regular meal the stomach is emptied more slowly
than when the food has a uniform consistency.

We have thus far spoken only of the movements of the
pyloric half of the stomach. How does the cardiac half
behave? For many years this has been looked upon as a
sort of reservoir for the swallowed food, but it has always
been considered purely passive, Cannon's experiments

MECHANICAL PHENOMENA. 13

show that it is indeed a reservoir, but a most active one.

The changes which (he cardiac half of the stomach suffers
during an ordinary digestive period is shown in the drawings,
which were made by tracing the outlines of the stomach on
tissue-paper laid over the abdomen of the cat at various
times after feeding.

By comparing .the figures it can be seen that as digestion
goes on the antrum seems to elongate and acquire a greater
capacity, and that the constrictions make deeper indenta-
tions into it (Fig. 2, 11.00-1.30). When the fundus has lost
most of its contents the longitudinal and circular fibres of
the antrum contract and make it shorter and of less capacity
once more. As compared with the changes in the form of
the rest of the stomach those in the antrum are slight.

The first region to decrease markedly in size is the pre-
antral part, at the beginning of which the peristaltic waves
commence. These gradually force some of the stomach
contents in this region into the antrum, so that the pre-
antral part little by little begins to assume a tubular form
in consequence of the sustained (tonic) contraction of the
muscle fibres of this region (Fig. 2, 1.30-2.30). At one
end of this tube we have the rounded fundus, at the other
the actively contracting antrum. Shallow constrictions may
pass along the tubular portion.

The muscle fibres (longitudinal, circular, and oblique) found
in the fundus gradually contract upon the spherical mass of
food found here and slowly force it into the tubular portion.
The size of the fundus thus gradually diminishes, until the
shadow cast by this portion of the stomach entirely dis-
appears (Fig. 2, 5.00-5.30). The tubular portion of the
stomach forces the food on into the antrum, until finally,
when the fundus is empty, the last remnants of food are
squeezed out of the tubular portion into the antrum.

We see from the above that the time which the food spends
in the stomach is considerably longer than is commonly
supposed. In the illustrations it can be seen that all the

14 PHYSIOLOGY OF ALIMENTATION.

food had not passed out of the stomach seven hours after
feeding. The same holds true for the human being, though
absolute quantity of food and its chemical and physical
character have much to do with its passage into the
duodenum. A large meal would, other things being equal,
take longer to leave the stomach than a smaller one. It
was pointed out above that coarse particles of food delay
the opening of the pylorus, and so keep a meal in the stomach
a correspondingly longer time. One of the pernicious results
of incomplete mastication of the food may well be traced
to this fact. We shall see below how the opening and closing
of the pyloric sphincter is affected still more powerfully by
the chemical constitution of the food.

We can readily appreciate the value of an organ which,
as the stomach, retains the swallowed food and only little
by little passes it on into the intestinal canal beyond. In
this way the food does not become heaped up in any sec-
tion of the small or large bowel until the rectum is reached,
and greater chance for the chemical elaboration of the vari-
ous foodstuffs and for their absorption is obtained in con-
sequence.

Having considered the movements of the stomach-wall,
we must discuss briefly the movements of the food within
the stomach. The older observations regarding this point
are very contradictory.

As was shown above, waves pass rhythmically over the
antrum. The food squeezed forward by an undulation
may have one of two things happen to it. If the pylorus
is open the wave serves to push the food on into the duo-
denum. We saw above, however, that by no means every
wave is effective in this direction. For the majority of
waves it might almost be said the pylorus remains closed.
Under these circumstances the food is forced into the blind,
pouch-like extremity of the antrum. When this occurs a
part at least of the food which is being pressed upon is forced
backward through the constriction towards the cardiac end

MECHAMCAL PHENOM EN A. 15

of the stomach. Cannon was able to show that the food
actually moves in this way by mixing with it starch-paste

pellets of bismuth subnitrate, the excursions of which could
readily be followed among the other food. When the pylorus
is closed the food is squirted back through the oncoming
constriction with considerable force. A subsequent wave
then carries the food toward the pylorus once more. In this
way the food is brought in contact with the mucous mem-
brane of the stomach over and over again, and thus besides
undergoing a certain degree of mechanical division becomes
thoroughly mixed with the gastric juice. Interestingly
enough, it is from this more active pyloric half of the stomach
that the largest secretion of gastric juice occurs.

While digestion is going on and all the time that the
antrum is most busily engaged in kneading and rekneading
the food in this portion of the stomach the food in the car-
diac half shows no sign of movement. Bismuth-subnitrate
balls contained in the food which lies in the fundus keep
their relative positions until the fundus begins to contract
and then move slowly forward toward the antrum. This
observation should settle for all time the question of salivary
digestion in the stomach. As is well known l the amylase
and maltase of the saliva do not act upon starch or maltose
respectively wThen even a small percent of any acid is pres-
ent. Careful examination of the fundus contents after a
starchy meal by Cannon and Day2 have shown that no_
inconsiderable amount of salivary digestion occurs in the
stomach. Herein we find another fact indicative of the
importance of thorough mastication and insalivation of the
food before it is swallowed. Food thus prepared can undergo
salivary digestion in the cardiac half of the stomach, perhaps
even for hours before it is brought to a standstill by becom-
ing mixed with the hydrochloric acid of the gastric secre-
tion.

' Seep. 103.

2 Cannon and Day: American Journal of Physiology

16 PHYSIOLOGY OF ALIMENTATION.

5. The Passage of Different Foodstuffs from the Stomach.
The Opening and Closing of the Pyloric Sphincter. — It

is the function of the pylorus, through the contraction
of the muscular fibres contained in it, to keep the gas-
tric contents from being forced out of the stomach whi'/e
subjected to the churning movements of this organ. At
certain times, however, the pylorus relaxes and allows a
part of the gastric contents to pass through. Some of the
older observers believed that the pylorus was contracted
during the entire digestive period and that only when the
food had been thoroughly mixed with the gastric juice did
it relax and allow the stomach to empty itself entirely and
at once. We know now, from the findings of Ewald, Boas,1
and Penzoldt2 with the stomach- tube, and the more per-
fect experiments of Cannon 3 with the x-rays, that the
stomach empties itself little by little through periodic open-
ings and closings of the pylorus. As has been shown above,
the peristaltic waves of the stomach pass continuously
under normal conditions from the middle of the stomach
to the pylorus. As long as the pylorus is closed these waves
serve only to churn the food and mix it thoroughly with
the gastric secretion. When the pylorus relaxes, how-
ever, these same waves serve to push the gastric contents
into the duodenum. What now determines this periodic
opening and closing of the sphincter?

Hirsch 4 observed in 1893 that when an acid is intro-
duced into the duodenum through a duodenal fistula the
escape of the gastric contents from the stomach is delayed
for some time. Serdjukow 5 confirmed this finding in 1S99.
About the time of Hirsch's observations, Penzoldt found

1 Ewald and Boas: Virchow's Archiv, 1885, CI, p. 364.

2 Penzoldt. Deut. Arch. f. klin. Med., 1893, LI, p. 545.

3 Cannon: Am. Jour, of Physiol., 1898, 1, p. 368.

4 Hirsch: Centralblatt fur klin. Medizin, 1893, XIV, p. 73.

5 Serdjukow: Russian dissertation reviewed in Hermann's Jahres-
bericht ub. d. Fortschritte d. Physiologic, 1899, VIII, p. 214.

MECHANICAL PHENOMENA. 17

that those foods which delay the appearance of free hydro-
chloric acid in the stomach remain longest in this organ.
More recently Cannon x has reinvestigated (his subject,
confirmed the findings of Penzoldt, and outlined a theorj
of the action of the pylorus which agrees with experimental
and clinical facts as we know them to-day.

Cannon investigated the rate at which different food-
stuffs leave the stomach to enter the small intestine. As
examples of a nearly pure protein diet, boiled beef free from
fat, boiled whitefish or the white meat of fowls was used.
Beef-suet, mutton-fat, or pork-fat served as nearly pure
fats, while starch paste, rice, and potatoes were taken as
examples of a carbohydrate diet. Definite amounts of the
various foods mixed with bismuth subnitrate were fed
to full-grown cats which had been without food for twenty-
four hours previously, and by means of the .r-ray the
rapidity was noted with which the various foodstuffs escape
into the intestine. The time at which the food begins to
move into the duodenum can be accurately determined in
this way, and by measuring the aggregate length of the
shadows in the small intestine at half-hour or hourly in-
tervals the relative amounts of food in the intestine from
time to time can be fairly well gauged.

In the following curves (Fig. 3) constructed from Can-
non's figures are indicated the different velocities with
which protein, fat, and carbohydrate leave the stomach.
It will be seen that the fats and carbohydrates begin to
move out of the stomach soon after ingestion, the carbo-
hydrates leaving very rapidly, while the fats leave only
slowly. The curve representing the carbohydrates (curve C)
rises rapidly to a maximum which is reached at the end
of the second hour, to fall more slowly after this point is
passed. The curve for fats (curve .1) both rises and falls
slowly, does not reach its maximum until the third hour,

1 Cannon: Journal <»t the \m. Med. Assoc, L905, XI. IV. p. 15.

18

PHYSIOLOGY OF ALIMENTATION.

and at no time even approaches the maximum points reached
by the carbohydrates or proteins. The protein curve
(curve B) possesses the greatest interest. Not only do
the proteins begin to pass out of the stomach much later
than either fats or carbohydrates (often none of the gas-

2 3 4

Hours after Feeding

Fig. 3.

A = fat; J3=protein; B' = acidulated protein; C = carbohydrate;
C" = alkalinized carbohydrate.

trie contents leave the stomach before the end of the first
hour after a protein meal), but their maximum velocity is
not attained until the end of the fourth hour. It will be
noticed that these findings harmonize with those of Penzoldt.
What now determines that carbohydrates upon which

Mechanical phenomena. 10

the gastric juice has iki effect should leave the stomach
quickly while proteins which are digested in the stomach
should remain here a long time? The observation of Pen-
zoldt that those foods which combine with the hydrochloric

acid of the stomach are t he last, to leave this viscus lias
been pointed out above. It is the presence of free hydro-
chloric acid in the stomach and near the pylorus thai deter-
mines the relaxation of the sphincter and explains why
different foodstuffs enter the small intestine at different rates.
As will be shown later 1 an abundance of gastric juice is
poured out on both a protein and a carbohydrate diet. A
diet consisting chiefly of fat causes the secretion of much
less juice. Now since carbohydrates cause a great secretion
of gastric juice but do not unite chemically with the acid,
free hydrochloric acid accumulates almost at once in the
stomach. Proteins, on the other hand, unite with the acid
of the gastric juice and hence prevent the accumulation of
free acid for a considerable length of time. Finally, fat
calls forth only a slight secretion of gastric juice, but that
which is produced soon accumulates in the stomach, as it
does not unite with the fat. These facts explain the dif-
ferent rates at which the various foods pass out of the
stomach.

The idea that it is the presence of free hydrochloric acid
in the stomach which determines the relaxation of the
sphincter can be still further tested. If a carbohydrate
meal is mixed with an alkaline fluid it delays the appear-
ance of free hydrochloric acid in the stomach. Such a meal
we find also leaves the stomach much later than the pure
carbohydrate. This is indicated in curve C" in Fig. 3. It
will be seen that the curve for alkalinized carbohydrate
tends to approximate that for ordinary protein.

It is possible to try the converse of this experiment by
feeding acidulated protein from which any excess of acid

1 See ( li;ipt r XT, Part 2.

20 PHYSIOLOGY OF ALIMENTATION.

has been removed and noting the rate at which this food is
discharged from the stomach. When acidulated protein is
fed, the hydrochloric acid of the gastric juice is allowed to
accumulate from the beginning. As is indicated in curve
B' in Fig. 3, corresponding to this fact, we find that acidu-
lated protein leaves the stomach as rapidly as pure carbo-
hydrate,— in fact, the two curves almost coincide.

It might be thought at first that the addition of an acid
to a pure carbohydrate meal would hasten its discharge
from the stomach. Experiment shows that this is not the
case, for a curve showing the velocity with which a meal of
crackers mixed with 0.4 percent hydrochloric acid leaves
the stomach practically coincides with that furnished
by an equally large meal consisting of crackers and water
only. How is this fact to be explained? We find an answer
in the observations of Hirsch and Serdjukow quoted above,
who found that the presence of an acid in the duodenum
causes the discharge of food from the stomach to be delayed.
Whether this was due to a contraction of the pyloric sphincter
or to a cessation of the movements of the stomach could,
however, not be determined in their experiments. We
know now from Cannon's researches that the peristaltic
movements of the stomach are continuous, so that Hirsch's
and Serdjukow's findings must be explained through a
contraction of the pyloric sphincter.

We see therefore that two factors are concerned in the
opening and closing of thepylorus. The pylorus opens when-
ever free hydrochloric acid of sufficient concentration is
present in the stomach. The opening of the pylorus allows
the escape of a part of the acid stomach contents into the
duodenum. As soon as the acid comes in contact with this
portion of the intestinal tract, however, the pylorus is made
to close and remains closed until the acid in the duodenum
is neutralized through the flow of the pancreatic juice and bile
into this portion of the gut. As will be shown later, the pres-
ence of acid in the duodenum is a determining condition

MECHANICAL PHENOMENA. 21

for the flow of juice from the pancreas.1 As the acid in the
duodenum becomes neutralized the stimulus to the closure
of the pylorus is weakened until the acid in the stomach
once more opens the sphincter. Another portion of food
in consequence escape? from the stomach, the pylorus closes
once more, and the cycle is repeated.

Automatically, therefore, carbohydrates which are not
acted upon by the gas!ric juice leave the stomach soon after
ingestion and quickly, while proteins which are digested
in this viscus are retailed and discharged only slowly. The
intestine is spared in ;his way large doses of acid stomach
contents which unless neutralized interfere so markedly
with the digestive functions of the intestine.

The behavior of fat differs a little from that of the carbo-
hydrates and proteins. The immediate but slower discharge
from the stomach is explained in part by the small amount
of gastric juice which is poured out upon fat. The gastric
peristalsis after a meal consisting mainly of fat is also not
as vigorous as that found after a meal of protein or carbo-
hydrate. Moreover, as soon as fats enter the duodenum the}7
cause the same closure of the pylorus which is caused by
acids.2 In this way the fats are kept for a long time in the
stomach.

1 See Chapter XII, Partt 2, 4 and 5.

2 Lintwarew; Biochemisches Centralblatt, 1903, I, p. 96, quoted
by Cannon.

CHAPTER II.

THE MECHANICAL PHENOMENA OF ALIMENTATION

(Continued).

6. The Movements of the Small Intestine. — A review of
the literature on the movements of the intestine, both large
and small, may be found in the articles of Grutzner x and
Cannon 2 and in the section on the intestine by Starling 3 in
Schaefer's Text-book of Physiology. The following para-
graphs sum up Cannon's conclusions on the movements of
the intestine as studied by the already outlined method of
rr-ray examination of the alimentary tract after a meal mixed
with bismuth subnitrate. Cats fed on canned salmon or
bread-and-milk mush were used for experimental study.

It is best to begin a description of the normal movements
of the small intestine by referring to Fig. 4, in which is shown
the appearance of the food in the intestine of a cat five and
three-quarter hours after a meal of canned salmon. The
animal is lying upon her back. In the middle of the plate
in dim outline is seen the spinal cord with the pelvis below.
On the right side above is the pyloric extremity of the stom-
ach, and below it in dark shadow several intestinal loops
lying over each other. In lighter outline and occupying the
entire abdominal cavity are other loops also filled with food.
The small dark shadow on the left is the caecum.

1 Grutzner: Pfliiger's Archiv, 1898, LXXI, p. 515.
? Cannon: American Journal of Physiology, 1902, VI, p. 251.
3 Stabling: Schaefer's Text-book of Physiology, Edinburgh and
London, 1900, II, p. 330.

22

]■"!.

(From an .r-ray photograph kindly sent me |>y 1 )r. C.vxxox.)

23

MECHANICAL PHENOMENA. 2">

When sufficient time has elapsed so that the food has been
distributed through the intestine as indicated in Fig. 4, and
the animal is exposed to the x-rays, it is found that mosl
of the loops are in a state of perfect rest. This is due only
to the excited state of the animal. After a time, if the
cat is allowed to remain quiet, the intestinal movements
begin. Two chief kinds of intestinal movement may then
be recognized: first, movements of rhythmic segmentation,
and secondly, peristaltic movements. By far the more com-
mon of these two movements is the first named. Sway-
ing movements, such as have been described by the older
observers, are also seen at times.

The character of the rhythmic segmentation can be best un-
derstood by reference to Fig. 5. The movements consist
essentially in the sudden division of one of the long narrow
strings of food lying in one of the loops shown in Fig. 4
into a large number of segments of nearly equal size. These
segments are then suddenly divided and neighboring halves
unite to form new segments, after which the process is re-
peated. This division and redivision of the food follow each
other many times in succession. In line 1 of Fig. 5 is shown
the food as it lies in a loop of intestine in the quiescent state.
Suddenly as the movements of rhythmic segmentation evidence
themselves, this string of food is divided into a large number
of nearly equal segments as indicated in line 2. A moment
later each of these segments is divided in two pieces, and
the neighboring pieces unite to form a new segment. Thus
a and b of line 2 unite to form the segment c of line 3. When
this division occurs the end segments A and B remain small.
But the next segmentation which divides the segments of
line 3 restores the old order of things, for the end pieces re-
unite with the halves of their adjoining segments to form
the new segments indicated in line 4. This series of seg-
ments it will be seen corresponds to the series shown in
line 2. The process of division and redivision of the food
continues under ordinary circumstances uninterruptedly for

26 PHYSIOLOGY OF ALIMENTATION.

more than half an hour, during all of which time the form
scarcely changes its position in the abdomen. In one
instance the segmentation was seen to continue with only
three short periods of inactivity for two hours and twenty
minutes.

The above description holds for the usual movements of
the small intestine, and when the food is not too thickly
crowded in that region of the gut. When too large an
amount of food is present in any given portion of the in-

i OCDOCDOcS A

600000^

Fig. 5.

(Copied from Cannon: American Journal of Physiology, 1902,

VI, p. 256.)

testine the constrictions may not completely divide the
string of food, but only in part. This condition of affairs
is illustrated in line 1 of Fig. 6.

Furthermore, the constrictions do not always take place
in the middle of a segment, but more toward one side of it,
as indicated by the dotted divisions in line 1 of Fig. 6. In
this way one-third of each segment may be pinched off at
each division, and only every third segmentation restores
the original order of the series. Thus, in Fig. 6, the first
division occurs along the dotted line a in each segment.
This brings about the state of affairs shown in line 2. In
this series the fragment of food at the extreme right of the
string consists of one-third of an original segment, while that
at the extreme left consists of about two-thirds of a segment.
The next division which takes place along the dotted
line b brings about the condition of affairs indicated in line

MECHANIC A L PHENOMENA.

27

3, in which two-thirds of an original segment is present on
the right-hand end of the string of food and one-third on
the left hand. Not until the third division occurs along the
dotted line c is the original arrangement of the segments
restored.

The rapidity with which the segmenting movements occur
is exceedingly interesting. If each segmentation, that is to
say, if every change from one line to another in the diagrams,
is counted, it is found that from twenty-eight to thirty occur
each minute. If the string of food is thin, only rarely does
the rate fall as low as twenty-three in the same unit of time.
When much food is present in a given segment of intestine,

J- * * w wc w

Fig. 6.

(Copied from Cannon: American Journal of Physiology, 1902,

VI, p. 258.)

as indicated in Fig. 6, the number may fall as low as eighteen
to twenty-one per minute.

Cannon has calculated that a slender string of food may
commonly undergo division into small segments more than
a thousand times without changing its position in the intes-
tine. The admirable purpose which this serves in thoroughly
mixing the food with the digestive juices and bringing it in
contact with the absorbing mucous lining of the intestine
will at once become apparent. Moreover, as Mall l has
pointed out these repeated rhythmical contractions greatly

1 Mall: Johns Hopkins Hospital Reports, I, p. 37.

28 PHYSIOLOGY OF ALIMENTATION.

aid in the propulsion of the blood into the portal circulation
and the movement of the lymph through the lacteals. As
absorption and secretion by the intestinal mucosa are both
markedly influenced by the character of the blood which
flows through this tissue, it can at once be seen how impor-
tant these rhythmical contractions are.

We turn now to a consideration of the peristaltic move-
ments in the small intestine. Peristalsis shows itself in two
forms, first as a slow advancement of the food for a short
distance in a coil, and secondly, as a rapid movement which
sweeps the food through several loops of the gut. The latter
is frequently seen under normal conditions when the food is
carried forward from the duodenum. It is produced arti-
ficially by injecting soap-suds into the rectum.

When a mass of food has been subjected to the already
described segmenting movements for a time, the latter may
suddenly cease and the separate segments begin to move slowly
forward, each segment following closely upon its predecessor.
After moving forward in this way for a few centimeters the
anterior segment comes to a stop, and the
succeeding ones are swept into it, until
a 6 the food lies stretched along the intestine

(3XZ) ^ as a solid, resting string of food.

Sometimes a single large mass of food,

^^2> cQ 3 sucn as *s indicated in Fig. 7, is pushed

forward. A long string of food is first

—*(^ > ^ crowded together into a more rounded mass,

such as is shown in line 1. Suddenly this

,n ■ lG.' ' ^ mass is indented in the middle and assumes
(Copied irom Can- .

non: American in consequence the shape shown in line

Journal of Phy- 2. A second division now occurs in the

siology, 1902, VI posterior portion a which may cause the

p. 260.) severed part to fly backward for some

distance in the intestine, when a succeeding contraction

again unites all the pieces into a rounded mass and pushes the

whole slightly forward. This is shown in line 4 of Fig. 7.

MECHANICAL PHENOMENA. 29

7. The Movements of the Large Intestine. — As will be
described in greater detail later the food passes from the
small intestine through the ileocecal valve into the ascend-
ing colon, and under normal circumstances this valve is
competent to the food which has passed through it. From
differences in physiological function we must distinguish
between the first portion of the large gut which is com-
posed of the ascending and transverse colon, and the second
portion which is made up of the descending colon. Not
only do the intestinal movements differ in these two por-
tions of the large bowel, but also their contents. For while
palpation shows that the food in the caecum, ascending and
transverse colons is soft, so that the walls of the gut can
readily be approximated, it is found that the contents of
the descending colon, sigmoid flexure, and rectum are made
up of hard, incompressible lumps.

By far the commonest normal movement of the ascending
and transverse portions of the large bowel is that of anti-
peristalsis, that is to say, the peristaltic waves visible in
this portion of the intestinal tract occur in a direction toward
the stomach and away from the rectum. The first food
which enters the colon from the small intestine is carried
by these anti-peristaltic waves into the caecum. The con-
tents of the colon are not, therefore, as is generally believed,
carried forward toward the rectum by a slow peristalsis,
but are instead pushed backward a large number of times
by these anti-peristaltic waves. These anti-peristaltic waves
begin at the most advanced portion of the food, or, if con-
siderable is present, at the splenic flexure, from which they
sweep backward toward the caecum. The average dura-
tion of a period of anti-peristalsis is four to five minutes,
and the periods recur every ten to twenty minutes. Between
the periods the colon is quiet.

As the ileocaecal valve is competent under normal circum-
stances, the anti-peristaltic waves do not force the food
out of the large intestine back into the small intestine.

30 PHYSIOLOGY OF ALIMENTATION.

The constrictions as they pass over the colon therefore
force the food into a blind pouch. As the food does not
burst through the caecum while subjected to the ever-in-
creasing pressure of the contractile ring it can only escape
through the advancing ring. We have already become
familiar with this phenomenon in the stomach when the
peristaltic waves pass over it against a closed pylorus.
In the colon, therefore, we have the food again subjected
to a thorough mixing, and another opportunity is pre-
sented for absorption.

The movements characteristic of the descending colon are
a series of tonic constrictions which pass downwards toward
the rectum. As the food accumulates in the ascending
colon it is at first confined to the region of anti-peristalsis.
As more food enters the ascending colon the contents of
the large bowel are forced over more and more into the
transverse and descending portions. After a time, as the
food approximates the splenic flexure a deep constriction
appears which pinches off a globular mass from the main
body of the food as indicated in A, Fig. 8. This constric-
tion persists, in other words, is
a tonic one. The globular mass
now moves slowly forward toward
the rectum, and as it passes
onward down the descending
FlG g# colon new constrictions appear

(Copied from Cannon: Amer- which again pinch off globular
ican Journal of Physiology, masses from the advancing food
1902, VI, p. 268.) column in the transverse colon.

This is shown in Fig. 9. These rings slowly move down
the descending colon, pushing the rounded masses of food
before them until they reach the sigmoid flexure and rectum.
Even during the short passage from the splenic flexure into
the rectum some absorption occurs, for the food masses
which are pinched off in the transverse colon are much
softer than the dry faeces which collect in the rectum.

(From an x-ray photograph kindly senl me by Dr. Cannon.)

31

Fig. 10.
(From an x-ray photograph kindly sent me by Dr. Cannon.)

33

MECHANICAL PHENOMENA. 35

8. Defaecation. — The act of defalcation is in pari an invol-
untary, and in part a voluntary, process. The first part of
the act is involuntary and may be described as follows- In
the cat the entire large bowel seems to swing around so thai
the ascending colon is raised to occupy in part the posit inn
formerly held by the transverse, and this
the position originally occupied by the
descending colon. This is apparent when
Fig. 11, which shows the beginning of the
act of defalcation, is compared with Fig. 10,
which shows the position of the large in-
testine under ordinary circumstances. The
tonic constrictions pictured in Fig. 10 dis-
appear at the same time, and their place is
taken by a single broad contraction of the
circular muscle which tapers off the in-
testinal contents on both sides of it. In
this way a faecal mass lying low in the
descending colon is pinched off from the F|G ^

intestinal contents higher up. The broad (Copied from Can-
contraction now passes slowly downward non. American
and, aided by the voluntary contraction of Journal oi Phy

the abdominal muscles and the voluntary ^ogy,vn. •

VI p. 2/0.)
relaxation of the anal sphincter, which con-
stitute the second part of the act of defaecation, pushes
the faecal mass out of the canal.

When the external act of defaecation has been thus accom-
plished, the colon with its remaining contents returns to
nearly its former position (Fig. 12). From the time that the
colon begins to change its position until it returns to it once
more takes about 20 minutes. When the original position
has been reassumed the slowly moving contractions begin
again, and the contents of the large intestine which were not
lost in the act of defaecation are slowly spread into the
emptied portion of the descending colon.

Just how the intestinal contents got from the region of the

36 PHYSIOLOGY OF ALIMENTATION.

anti-peristaltic waves in the colon to the region of the slowly
advancing rings is not yet entirely understood. In part the
later portions of the food push that which has gone before
ahead of it. But the ascending and transverse portions of the
colon can get rid of most of their contents even in starvation,
though they are, perhaps, never entirely emptied even under
these conditions. Apparently strong tonic peristaltic waves
at times pass over the ascending and transverse colon and
force the contents of these portions of the large bowel into the
region of the descending colon, where peristaltic waves are the
rule.

9. The Movement of Food through the Alimentary Tract
as a Whole. — The process of mastication takes a varying
length of time, depending upon the nature of the food and to
a large extent upon the individual. Dry food takes longest
to become mixed with saliva sufficiently to allow of its being
swallowed, while liquids are at once passed backward toward
the oesophagus. The entire length of time required for the
food to fall into the stomach after mastication is completed
varies with different animals, the extremes being represented
by four and twelve seconds. In man from four to seven
seconds are required from the initiation of the act of deglu-
tition to the time the food falls into the stomach.

The food remains in the stomach a variable number of
hours, depending upon the quantity and the quality of the
food ingested. Other things being equal, a small amount of
food will escape into the small intestine in shorter time than
a larger amount. The time that food remains in the stomach
is probably greater than is generally believed to be the case.
An average meal does not ordinarily leave the stomach en-
tirely in less than six hours. The quality of the food plays
an important role by determining the frequency with which
the pyloric sphincter relaxes and allows the food to be forced
onward into the duodenum by the contractile waves which
pass over the antrum. As was shown above, not every wave
forces food out of the stomach.

Fig. l

(From an x-ray photograph kindly sent me by Dr. Cannon.)

MECHANICAL PHENOMENA. 39

When the pylorus relaxes the food is squirted for a con-
siderable distance along the duodenum (Fig. 13), where it lies
quietly until added to by further contributions from the
stomach. In this way a long thin string of food is formed.
During all this time the pancreatic and bile ducts pour the
secretions from their respective organs into the food. All at
once the string of food breaks up into several segments, and
the process of rhythmic segmenta-
tion already described above is 0
started. After this has continued for o

some minutes the segments unite

o
into a single large mass, or into 0 Fig. 13.

groups, and slowly pass along the (Copied from Cannon:

gut. Near the pylorus the peristalsis Ame"can Jo"rnal of

■w,i , • +u Physiology, 1902, VI,

is more rapid than lower down in the lco .

1 p. 2b2.)

small intestine. "The masses once

started go flying along, turning curves, whisking hither and
thither in the loops, moving swiftly and continuously for-
ward." L After passing forward in this way for some dis-
tance the food is collected again into thick and long strings
and the process of segmentation repeated. The strings
of food may remain lying quietly in a loop of intestine
for an hour or more. During the first stages of digestion the
food lies chiefly on the right side of the abdomen, during the
later stages chiefly on the left. By these combined move-
ments of segmentation and peristaltic advance, both of which
are repeated from time to time, the food is finally brought to
the ileocecal valve.

The time elapsing before the food enters the duodenum
from the stomach varies, as already pointed out, with
the nature of the food. In general it may be said that no
food enters the small intestine until one or one and a half
hours after eating. Five to six hours elapse after eating
before food begins to appear in the large intestine, so that it

1 Cannon: American Journal of Physiology, PKI'i, VI, p. 2t>.'J.

40 PHYSIOLOGY OF ALIMENTATION.

is evident that approximately five hours are required by the
food to traverse the small intestine.

The food about to pass into the large intestine is directed
toward the latter from some distance back in the small gut (see
Fig. 8, B). From here it moves slowly along the ileum and is
pushed through the valve into the colon to fall into the
caecum. This passage of food through the ileocecal valve
seems to act as a stimulus which excites the colon to activity.
As the food approaches the ileocaecal valve the large intestine
is quiet and relaxed. As soon, however, as the food has
entered it a strong contraction takes place along the ceecum
and lower portion of the ascending colon, which is followed
immediately by the anti-peristaltic waves which have already
been described and which continue running for two or three
minutes.

Under ordinary circumstances the succeeding masses of
food force the older portions onward through the large
bowel, but even in starvation most of the contents of the
large bowel are gotten rid of. But a complete emptying
of the large intestine seems never to occur. The time
which the food spends in the large intestine varies of course
with the intervals elapsing between succeeding defsecations.
The time which the intestinal contents spend in the ascend-
ing and transverse portions of the large bowel is certainly to
be measured in hours. During all this time absorption is
actively going on. As the food passes into the descending
colon, sigmoid flexure, and rectum this absorption is probably
considerably diminished.

The voluntary part of the act of defalcation is preceded
by an involuntary act of preparation which takes an hour
or more. This is the time required for the intestinal con-
tents to pass from above into that portion of the lower
bowel which has been emptied by the last act of defsecation.
The voluntary part of the act of defsecation takes only a
few seconds, depending upon the amount and consistency
of the defalcated mass.

MECHANICAL PHENOMENA. 41

10. The Nervous Control of the Alimentary Tract. — We
are still far from a correct understanding of the relation of
the nervous system to the movements of the various parts
of the alimentary tract. The experimental results obtained
by the score of investigators who have busied themselves
with this problem do anything but harmonize, a fact not
strange when the difficulties standing in the way of the
solution of the problem are considered. Narcotics, operative
procedures, etc., all so markedly influence the movements
of the alimentary tract that when these constitute the neces-
sary means which must be utilized in a study of the problem
uniform results can scarcely be expected. The following
paragraphs follow in the main Starling's1 recent review of
the subject.

The act of deglutition is only in part voluntary, and may
as a whole be considered as an essentially reflex act. The
reflex is initiated whenever the palatine branches of the tri-
facial, the glosso-pharyngeal, and superior laryngeal nerves
are stimulated either through the presence of food or saliva
in the mouth or by artificial means as when an electrical
stimulus is applied to the central end of the divided superior
laryngeal nerve. The afferent nerves pass into the medulla,
in the upper portion of which is situated a "centre" whose
destruction is associated with impairment or total loss of the
power to swallow. The impulses which go to bring about a
movement of the muscles concerned in the act of swallowing
leave the medulla chiefly by way of the trifacial, facial,
and glosso-pharyngeal. The oesophagus is supplied almost
solely by the vagus.

The oesophagus has the power of spontaneous peristaltic
contractions ; within the body, however, the waves which
pass over the oesophagus in the ordinary act of swallowing
seem to be intimately connected with an uninjured nervous
system. Division of the nerves supplying the <vsophagus

r

1 Starling: Ergebnlsse der Physiologic, L902, 1, 2te Abth., p. 446.

42 PHYSIOLOGY OF ALIMENTATION.

causes a stoppage of the oesophageal movements. Simple
ligature of the oesophagus without injury to the nerves does
not, however, keep the oesophageal movements from passing
over the entire length of the oesophagus. A piece can even
be cut out of the oesophagus and if the nervous connections
between the upper and lower ends have not been injured the
swallowing movements inaugurated in the upper end pass
(by way of the nerves) over the lower end also. It seems
therefore as though the ordered act of deglutition which is
started through stimulation of certain afferent nerves is
dependent in the last analysis upon impulses which pass
from an excited "centre" by way of certain efferent nerves
to the oesophagus, one segment after another of which is
thereby made to contract.

The stomach is supplied with cranial nerves by way of the
two vagi, and with sympathetic nerve fibres by way of the
splanchnics and the solar plexus. The vagi contain fibres
which not only bring about movements in the stomach
but also such as inhibit movement. Under ordinary circum-
stances, more especially when the stomach contains food,
stimulation of the vagi brings about a contraction of the
cardiac end of the stomach; or one or a series of contractions
arise in the preantral portion of the stomach; or, finally,
the musculature of the whole stomach may go into a state
of tonic contraction which gradually increases and then
after a longer or shorter period of sustained contraction as
gradually relaxes. Under certain circumstances stimulation
of the vagi may have an opposite effect. Especially after
the administration of pilocarpin may stimulation be followed
by muscular relaxation. The sympathetic nerves supplying
the stomach in a certain sense antagonize the action of the
vagi. If the splanchnic nerves are stimulated a decrease in
the tonus of the gastric musculature as well as a decrease
in the rhythmical contractions of the stomach are usually
observed.

In addition to the nerves which run into the wall of the

MECHANICAL PHENOMENA. 43

stomach, there exist in this viscus isolated ganglion cells
and nerve fibres from the plexus of AuERBACH and Meissner.
These local nervous elements have been looked upon as
causing the rhythmical contractions of the stomach, but
it is questionable whether the unstriped muscle fibres are
not themselves responsible for this. It approximates cor-
rectness most nearly, no doubt, when we say that the un-
striped muscle fibres of the stomach are capable of the
rhythmical and the sustained contractions which we observe
in this organ, but that these contractions can be markedly
influenced through the nervous system.

In addition to the local nerve-cells and plexuses, and the
vagus and sympathetic fibres which go to the stomach,
there exist in the spinal cord and the ganglia at the base
of the brain so-called "centres" which on stimulation lead
to muscular contractions or relaxations in the stomach, but
we do not understand how these different elements cooperate
to bring about the ordered movements observed in this viscus
after an ordinary meal, or the disturbances noted in certain
pathological states.

The small intestine is supplied by branches from the vagus
nerves and from the sympathetic system. The sympathetic
fibres come to the intestine in part from the solar and lum-
bar plexuses, in part by way of the splanchnics. Stimu-
lation of the vagus brings about in the small intestine as
in the stomach motor effects which may evidence them-
selves in rhythmical contractions, or in sustained tonic con-
tractions. The chief effect of stimulation of the sympa-
thetic fibres seems to be that of inhibition. As was first
shown by Pfluger, stimulation of the splanchnics leads to
cessation of movement in the small intestine. From Mall's l
careful studies it is known that an anaemia of the intestines
causes a cessation of movement in them, and it was once
thought that the inhibition of movement when the splanch-

1 Mall: Johns Hopkins Hospital Reports, 1SD6, I, p. 37

44 PHYSIOLOGY OF ALIMENTATION.

nics are stimulated was secondary to the anaemia brought
about by this means. But, as Bayliss and Starling have
shown, such inhibition of intestinal movement still follows
stimulation of the splanchnics in freshly killed animals,
in other words, when no circulation is present. Nothing
definite seems to be known regarding the role of the plexuses
of Auerbach and Meissner in the small intestine. Whether
they are, in the last analysis, responsible for the rhythmical
contractions of the jejunum and ileum seems questionable.
This power probably resides in the musculature itself.

Stimulation of certain regions in the ganglia at the base
of the brain and certain portions of the spinal cord leads
to muscular contractions or relaxations in the small in-
testine by way of the vagus and sympathetic nerves supply-
ing the gut. Some connection must also exist between the
cerebrum and the small intestine, for, as the next para-
graphs show, mental states may cause a stoppage of all
movement.

It has long been a recognized clinical fact that emo-
tional states such as fear, anxiety, sorrow, etc., bring
in their train a long series of digestive disturbances.
The physiological pathology of these disturbances has re-
cently been put on a more scientific basis by a series of
experimental observations. We shall later become ac-
quainted with facts which indicate how largely certain secre-
tory phenomena of the alimentary tract are influenced by
psychic states. Here mention must be made of the important
relation which exists between mental states and the move-
ments of the stomach and intestine.1

Cannon observed in his studies of gastro-intestinal move-
ments that female cats were much more suitable for
experimental purposes than males. Even though treated
exactly alike the movements which appeared almost with-

1 Cannon: American Journal of Physiology, 1898, I, p. 380; ibid.,
1902, VI, p. 260.

MECHANICAL I'll MOM EN A. 45

out exception in female cats were almost as constantly
wanting in male cats. Accompanying this was always a
difference in the behavior of the cats when bound into
the holder for observation. While the females would lie
quietly and purr, the males would fly into a rage and
struggle to get free. The following observation showed
the direct connection between the mental state and the
movements of the gastrointestinal tract. A male cat
which had been fed an hour and a half previously was tied
into the holder. The waves were passing regularly over
the stomach at the rate of six a minute. This had not
lasted long when the cat fell into a rage and all movement
in the stomach ceased at once.

A similar relation exists between the mental state and
the movements of the intestine. This is not surprising
when it is remembered that the nerves which are distributed
to these two portions of the alimentary tract are the same.
Whenever a cat becomes enraged and for some time after
it is again pacified the movements of the small and large
intestine cease entirely. Even when an animal is only
slightly restless in the holder no intestinal movement may
be apparent. In a continuously
fretful cat this may continue for
an hour. Between the periods of
excitement the intestinal move-
ments go on in a normal manner.
When the segmenting movements
in the small intestine cease, the
segments of food coalesce to form
a single long string. In Fig. 14, pIG< ^4

A, is shown the appearance of the (Copied from Cannon: Ameri-
Iarge intestine when the anti-per- can Journal of Physiology,
istaltic waves are running nor- 1902, VI, p. 275.)
mally, and in Fig. 14, B, how the same region of the intestine
looks when the anti-peristaltic waves are inhibited through
excitement. Interesting is the fact that the tonic contrac-

46 PHYSIOLOGY OF ALIMENTATION.

tions of the descending colon are apparently not affected by
emotional states, for they do not relax in the excitement
which causes the other movements to cease.

Inhibition of intestinal movement is not the only conse-
quence of excited mental states Cannon quotes the ex-
periments of Esselmont and Fubini to show this. Essel-
mont found that in the dog signs of emotion always markedly
increase the motor activities of the intestine, though only for
a few moments. Fubini noted that fear brings about an
increased peristalsis.

Finally, the fact must be mentioned that all movements of
the intestines go on during sleep in the same way as in the
waking hours.

ii. On the Action of Saline Cathartics. — According to the
generally accepted view those salts which are classed under
the head of the saline cathartics in the works on pharmacology
are believed to exert their action by preventing the absorption
of water from the intestinal contents as the latter pass through
the alimentary tract. In this way it is believed that the
ordinary inspissation into the compact faeces which collect in
the lower bowel is prevented, and the intestinal tract is rid
of its contents in the form of very soft or even liquid stools.

It seems from experiments recently carried out by J. B. Mac-
Callum 1 that this conception can no longer be looked upon as
the correct one. MacCalltjm's experiments were performed
chiefly on rabbits, but dogs and cats were also employed.
The salts used were sodium citrate, sulphate, tartrate, oxalate,
phosphate, and fluoride, barium chloride, and magnesium sul-
phate. These experiments have shown that the saline purga-
tives act not only when introduced into the intestine, but also
when injected subcutaneously or intravenously. They act
most powerfully, however, when applied directly to the peri-
toneal coat of the intestine. When 5 to 10 c.c. of a one-

1 MacCallum, J. B.: American Journal of Physiology, 1903, X, p.
101; Pfliiger's Archiv, 1904, CIV, p. 421.

MECHANICAL PHENOMEN I. 47

eighth molecular1 sodium citrate solution are injected into
the lumen of the intestine of a rabbit, increased peristaltic
movements manifest themselves in 10 to 15 minutes. About
the same length of time is required when the same amount of
this salt solution is injected subcutaneously. When, how-
ever, only 1 to 2 c.c. of this sodium citrate solution are
injected intravenously, a striking increase in intestinal move-
ments is visible in one to two minutes. It almost seems from
these experiments that the saline cathartics must be ab-
sorbed from the intestinal tract before they can produce their
specific effects. A reaction in the form of a local constriction
of the musculature of the gut is obtained almost immediately
after painting one of the saline cathartics on the peritoneal
coat of the intestine.

When equimolecular 2 solutions are compared, it is found
that by far the most powerful of the cathartics listed above
is barium chloride, after which come the citrate, fluoride,
sulphate, tartrate, oxalate, and phosphate of sodium, the
intensity of the action of which decreases approximately in
the order named. The intravenous injection of a solution con-
taining a few milligrams of the dry salt is sufficient to bring
about powerful contractions of the intestine. The power of
the various salts to produce their cathartic action was deter-
mined by discovering the lowest concentration in which they

1 That is, a solution of sodium citrate made by dissolving one grain-
molecule of the dry salt in enough water to make eight litres. A gram-
molecule of a substance is the molecular weight of that substance (plus
the molecular weight of its water of crystallization, if it has any) ex-
pressed in grams.

2 That is, solutions containing the same number of gram-molecules of
the various salts dissolved in the unit volume of the solvent (water in
this case). The comparison of equal percentage solutions, that is
solutions containing the same weight of the salts in the unit volume of
Bolvent, as was generally done by the older observers, leads to entirely
erroneous conceptions of the relative activity of the dissolved salts.
It would be well if all workers in experimental medicine would employ
only chemically equivalent solutions.

48 PHYSIOLOGY OF ALIMENTATION.

were effective. Magnesium sulphate is about as active a
cathartic as sodium sulphate, but it is by no means as harm-
less as the latter. MacCallum found that magnesium sul-
phate was often fatal in doses in which sodium sulphate is
entirely harmless. This statement is confirmed by some of
my own experiments on glycosuria, in which it was found that
the action of the sulphate of sodium is less harmful than that
of magnesium. The poisonous action is apparently deter-
mined by the magnesium constituent in the latter salt, which
has a powerful effect upon the heart. A practical conclusion
to be drawn from this is that it is better to give the sodium
salt to patients than the magnesium salt. The intensely
poisonous action of the barium chloride should also put a ban
upon the use of this drug in medicine. The fluoride and
oxalate also have specific poisonous properties which speak
against their use in medicine, especially when apparently
harmless salts may be employed with just as good results if
only care be taken to use the right amounts.

The purgative action of the saline cathartics depends upon
yet another factor than the mere increase in the peristaltic
movements of the intestine, namely, an increased secretion
of fluid into the intestine. This fact was observed by Gumi-
lewski * and Rohmann,2 and is confirmed by MacCalltjm's
observations. If a loop of intestine is tied off and a saline
cathartic is injected subcutaneously or intravenously, or is
simply painted on its surface, a secretion of fluid into the
loop of intestine is observed in addition to the increased
peristalsis.

MacCallum has been able to show that the effect of the
saline cathartics enumerated above, both in bringing about
an increased peristalsis and an increased secretion of fluid
into the intestine, can be counteracted by calcium chloride,
and to a less extent by strontium and magnesium chloride.
This antagonism between sodium and calcium salts seems to

1 Gumilewski: Pfliiger's Archiv, 1886, XXXIX, p. 556,

2 Rqhmann: Pfliiger's Archiv, 1887, XLI, p. 411,

MECHAXICAL PHENOMENA. I!)

exist in a variety of physiological reactions. Ringer '
called attention to it in his experiments on heart muscle. He
found that the contractions of ships of this tissue, which are
beating rhythmically in sodium chloride solutions, can be
inhibited through the addition of a calcium salt to the sodium
chloride solution. The experiments of Loeb, who has elab-
orated those of Ringer, show that the same antagonism exists
in the case of voluntary muscles and in nerves. Experiments
of other investigators are at hand which show that the antag-
onism between calcium and sodium salts exists in the involun-
tary muscles also, but these experiments are not entirely free
from criticism, for no special means were taken to exclude the
effects of nerve fibres or nerve-cells present in the preparations.
Whether the increased peristalsis is brought about directly
through the action of the saline cathartics upon the muscle-
cells themselves or only indirectly through an action of the
salts upon the nerve plexuses of Auerbach and Meissner has
not as yet been definitely settled. It is certain that we do
not need to go beyond the wall of the intestine for an ex-
planation of the action of these drugs. This is proven by the
fact that pieces of gut ligatured and cut out of the body will
show their characteristic movements when immersed in solu-
tions of the various salines. A secretion of fluid will even occur
into such pieces of intestine. This indicates that the ex-
planation of this phenomenon too does not lie beyond the
walls of the alimentary tract. From the fact that very
dilute solutions of the cathartics produce very violent and
yet entirely local contractions in the intestine when painted
upon its peritoneal surface it seems highly probable that the
increased peristalsis is brought about through a direct action
upon the muscular coat. If a stimulation of nerves lay at
the foundation of the increased intestinal movements we
would expect a more general effect from the local applica-
tions of the cathartic salts.

1 Ringeu: Journal of Physiology, 18S4, V, p. 247.

50 PHYSIOLOGY OF ALIMENTATION.

iSo far as the quantitative relation is concerned which
exists between the dose of a saline purgative sufficient to
affect the intestine and that of calcium chloride sufficient
to suppress the increased peristalsis and intestinal secretion
brought about by the former, it may be said that a chemically
equivalent amount of the one just counteracts the other.
If, for example, a certain number of cubic centimeters of a
1/8 molecular sodium citrate solution are injected into a
rabbit it requires an equal volume of a 1/8 molecular calcium
chloride solution to counteract the effect of the former. This
counteraction takes place almost immediately if the calcium
chloride is applied to the peritoneal coat of the intestine.
If the calcium chloride is injected intravenously it shows
its specific effect in one to two minutes, but it takes ten to
twenty minutes if it is injected subcutaneously or into the
lumen of the intestine.

MacCallum is inclined to explain the action of the saline
purgatives through their power of diminishing the concen-
tration of the free calcium ions in the tissues upon which
these cathartics act. This is the same explanation that Loeb
gives of the twitchings observed by him when voluntary
muscles are immersed in these same salt solutions. The
addition of a calcium salt therefore counteracts the effect of
the saline cathartics by restoring the concentration of the
calcium ions and so bringing the intestine back to its original
state. It must be remembered, however, that barium
chloride is the most powerful of all the salts studied, and
yet it is difficult to see how the administration of such traces
of this substance as are necessary to bring about a violent
catharsis is to be explained by its effects in reducing the
concentration of the free calcium ions. Hofmeister's belief
that Gatharsis is brought about through the coagulation of
certain colloids by the cathartic salts seems less open to
objection.

The movements of the intestine, as a whole, under the
influence of saline cathartics have not yet been studied.

MECTIA NIC. 1 /. PHENOM EN A . 51

Whether they are merely exaggerated forms of the normal
movements or differ materially from the latter cannol there-
fore be said with definiteness. That food takes a very much
shorter time to pass the length of the alimentary tract under
the influence of saline cathartics is a well-known clinical
fact, and has often enough been proven experimentally by
feeding inert substances and determining the time required
before they appear in the freces. The greater fluidity of the
stools we must, in the face of these recent experiments,
attribute to the increased secretion of fluid into the intestine
and not to a decreased absorption. That less of the food
is absorbed when saline cathartics are administered shortly
after a meal is in part dependent, no doubt, upon the in-
creased velocity with which the food traverses the bowel.
Less time is allowed in consequence for the products of
digestion to diffuse through the intestinal mucosa.

The cause of the pain (colic) which follows the ingestion
of the saline (and other) cathartics is also not entirely under-
stood. S. J. Meltzer has made an interesting study of the
subject. This author holds the increased force of the con-
tractions and their irregularity responsible for the pain
in all forms of intestinal colic.

Further work with the rc-rays would teach us much regard-
ing the movements of the intestines as a whole under ab-
normal conditions. That after the administration of the
saline cathartics it is probably a rapid sweeping peristalsis
which advances the food through several coils of intestine,
instead of the normal slow peristalsis which moves the food
onward only a short distance, seems very probable from a
statement made by Cannon,1 who observed this form of
movement in the small intestine as a regular consequence of
the injection of soap-suds. Many of the soaps resemble in
their action the saline cathartics.

12. The Fate of Nutrient Enemas. — While certain clinical

1 Cannon: American Journal of Physiology, 190'-', VI, p. 200.

52 PHYSIOLOGY OF ALIMENTATION.

observers have been unanimous in claiming that nutrient
enemas introduced into the rectum are absorbed and utilized
by the patient, others have been equally certain that they
are of little or no value. The burden of evidence is, how-
ever, in favor of the good results which are obtained by
this method of artificial feeding. Lack of success is no
doubt in large measure due to mistakes made in the com-
position of the enemas used, for the absorption of many
foods can occur from the intestinal tract only after they
have been acted upon by the digestive juices.

Leaving aside for the moment the chemical aspects
of the problem, two great objections have been brought
against the efficacy of rectal feeding. The first of these
is that the rectum has no powers of absorption, the second
that the food does not pass from the rectum to a portion
of the bowel, where it can be absorbed. It must be con-
fessed that experimental evidence has until recently been
largely in favor of these views. With scarcely an exception,
investigators have come to the conclusion that food intro-
duced into the rectum does not move far away from it.
Against this idea has stood Grutzner,1 who found that when
certain easily recognizable substances, such as starch grains,
hair, or charcoal, suspended in normal salt solution are
injected into the rectum they are carried upward through
the bowel into the small intestine, even as far as the stomach.
More recently Cannon 2 has brought direct proof of the move-
ment of nutrient enemas from the rectum, not only through
the large intestine but even into the small intestine. If we
admit, therefore; that the rectum has but feeble or no powers
of absorption, we can no longer maintain that the enemas
are not moved to a place in the intestine in which ab-
sorption is possible. The following may help to elucidate
what has been said:

1 Grutzner: Deutsche med. Wochenschrift, 1894, XX, p. 897.

2 Cannon: American Journal of Physiology, 1902, VI, p. 272.

MECHANICAL PHENOMENA. 53

In order to ascertain the fate of enemas, Cannon intro-
duced various amounts of thick and thin food mixtures,
holding bismuth subnitrate powder in suspension, into the
previously cleaned rectum of various animals and observed
what happened by means of the x-rays. The enemas had
the following composition:

100 c.c. milk,
2 grams starch,

1 egg»
15 grams bismuth subnitrate.

To make the enemas thick all these were stirred together
and boiled to a soft mush. To have them thin the egg
was omitted until after boiling, when it was added to the
cooled mass. The amounts injected varied from 25 c.c.
to 90 c.c, which was about sufficient to fill the large bowel
of the animals experimented upon.

Besides depending upon mere observation, radiographs
were taken at various intervals, in order to show the dis-
tribution of the injected enemas. After a control radio-
graph had shown the absence of any bismuth-containing
food in the intestine of the animal to be experimented upon,
the food was introduced into the rectum. It was found
in these experiments that when only small amounts are
injected they lie at first in the descending colon. In every
case, however, anti-peristaltic waves commence and the
food is carried through the transverse and ascending colon
into the caecum. Small injections of nutrient material
never pass this point. The larger injections, however, do
not stop when they reach the ileocaecal valve, but pass through
it high up into the small intestine. Strange as it may seem,
this valve, which is competent to the food passing through
it in the normal progress of the food from the stomach to
the rectum, allows the nutrient material from large rectal
enemas to pass through into the small intestine. The anti-
peristaltic waves of the ascending colon seem to be the
effective agents in forcing the enema backward through

54 PHYSIOLOGY OF ALIMENTATION.

the ileocecal valve and along the ileum, for when the valve
first allows the food to pass through, it pours into the
small intestine and appears as a mass which suddenly fills
several loops of the gut. Anti-peristalsis does not appear
in the small intestine though it continues in the large. After
the food has been in the small intestine for some time, the
typical segmenting movements appear, which divide and
redivide the food in the manner already described above.

Figs. 15, 16, and 17 are radiographs which indicate how
the food is forced after a large enema more and more from
the large intestine into the small. An enema of 90 c.c.
was given at 1.40 p.m. The first radiograph shows how
at 1.50 p.m. the food is evenly distributed through the large
intestine and through several loops of small intestine. In
the second and third radiographs, taken at 2.15 and 3.00 p.m.
respectively, the food is seen to have left the large intestine to
a great extent, and to be occupying an increasingly greater
number of loops of small intestine. Observations made at
3.00 p.m. showed segmentation to be going on in many
of the loops.

The importance of the ascending and transverse portions
of the large intestine as an absorptive organ has already
been pointed out, and it is not surprising, therefore, to find
evidences of this same absorption when food is introduced
into the intestinal tract by way of the rectum. In the
region of the anti-peristaltic waves in the large intestine the
shadows become progressively lighter, until in the end the
bismuth seems to be covering only the walls of the gut.
In the descending colon the shadows retain their original
opacity. When the rectal injections are large, the small
intestine also comes into play as an absorptive organ, and
this in the same way apparently as when the food is intro-
duced through the mouth.

It must be pointed out, finally, that if any digestive juices
are present in the large and small intestines, these are of
course mixed with the nutrient enemas and so are given an

I'm. 1.

(From an x-ray photograph kindly senl me by Dr. Cannon.

.-,:,

Fig. Hi. 2.15 p.m.
(From an rc-ray photograph kindly sent me by Dr. Cannon.

Fig. 17. 3.00 p.m
< From an x-ray photograph kindly Bent me by Dr. t'w

MECHANICAL PIIEXOMENA. 61

opportunity of exerting their specific effects. How much of
such a secretion occurs, and its quality, can, however, only
be surmised. If no food has been introduced through the
mouth, and no "psychic" or other secretion from the stomach
lias in consequence been called forth, little or no pancreatic
or intestinal juice of any kind may be present in the intes-
tine. This urges upon us the necessity of introducing into
the rectum only those foods which can be taken up directly by
the lower portions of the alimentary tract. Certain foods
are already in this condition, while others must first be
digested outside of the body, or have introduced along with
them those ferments which are found in the body and are
capable of so acting upon the various constituents of the
nutrient enemas that they are converted into readil}7 absorb-
able substances. Unless this chemical side of rectal feeding
is considered, we must fail in the objects which we wish to
attain by these artificial means.

CHAPTER III.

THE JUICES POURED OUT UPON THE FOOD AND THEIR
CHEMICAL CONSTITUENTS.

I. The Saliva. — This is the name applied to the mixed
secretions from the salivary glands and the mucous glands
of the mouth. The salivary glands are three in number,
the parotid, submaxillary, and sublingual, and as their secre-
tions differ somewhat they are best considered separately.

Human parotid saliva can be obtained by introducing a
fine cannula into Stenson's duct. In this way a clear, watery
liquid mixed with some epithelial cells and occasionally a
few leucocytes is obtained. The reaction is usually given
as faintly alkaline, but this seems to be incorrect. It is
probably neutral, perhaps even slightly acid.

The amount secreted in twenty-four hours varies within
wide limits physiologically. Ohl gives 80 to 100 c.c. The
specific gravity varies under physiological conditions and is
stated to be between 1.006 and 1.012. The parotid secretion
contains mucin and only traces of proteins. It contains the
starch-splitting ferment amylase and the maltose-splitting
ferment maltase. It also contains sulphocyanic acid in com-
bination with the metals found universally in the tissue
fluids. The exact amount of each of these substances varies
under physiological conditions, so that it is not surprising
that the figures given by different investigators do not agree
very well. Mitscherlich found 14 to 16 parts, Hoppe-
Seyler about 7 parts of solids in 1000 of parotid saliva.
About half of this amount is organic, the rest inorganic.

62

Tin: JUICES POURED OUT UPUS THE food. 63

Potassium sulphocyanate is present to (lie extent of about
3 parts in I0.000.1

Human submaxillary saliva may bo obtained in :i way
similar to that described above for obtaining parotid saliva,
namely, insertion of a fine cannula into Wharton's duct.
When the sublingual gland does not open into the mouth by
a separate duct, but discharges its secretion into Wharton's
duct, the two secretions can be separated by pushing the
cannula far enough along the common duct to pass beyond
the opening from the sublingual gland.2 The secretion ob-
tained in this way is clear and watery and of a specific
gravity somewhat lower than that of the parotid. It is
variously stated to be from 1.0026 to 1.0250, and is subject to
considerable variation under physiological conditions. The
amount of solids contained in the submaxillary saliva is
between 4 and 5 parts in 1000, against 6 to 15 parts found
in parotid saliva. The character of the solid constituents
is much the same as in the parotid saliva, except sulpho-
cya nate, the presence of which is questioned by some authors.
Sulphocyanate is certainly present in less amount in the
submaxillary secretion than in the parotid. This amount as
well as the quantity of submaxillary saliva secreted in any
unit of time varies greatly under physiological conditions.
Roughly speaking, the total amount secreted in twenty-
four hours is three times as great as that secreted by
the parotid (Ohl).3 The reaction is generally stated to
be alkaline, more probably, however, it is neutral. The
starch-splitting activity of the submaxillary saliva is very
great.

Ohl seems to be the only investigator who ever obtained
human sublingual saliva in sufficient amount to determine
thai it contains amylase, sulphocyanate, and mucin.

lVlBRORDT. lal'illcn, .leiKi, 1X88, p. 30.

2 See Moore: Text-book of Physiology, edited by Schaefer, Edin-
burgh, 1898, 1, p. 312.

3 Vierordt: Tabellen, Jena, 1888, p. 130.

64 PHYSIOLOGY OF ALIMENTATION.

The mucous glands of the mouth secrete a small amount of
an exceedingly tenacious material containing much mucin.
This secretion has never been obtained pure in the human
being, but experimentally it has been gotten from dogs after
ligature of the ducts or extirpation of the entire set of salivary
glands. The secretion is mixed with many epithelial cells
from the mouth.

The mixed saliva is that usually employed for experimental
purposes. The amount of this secretion in twenty-four hours
is stated by Bidder and Schmidt 1 to be 300 to 1500 c.c. The
quantity secreted in the unit of time is largest during meals
and falls to a minimum between meals. These variations will
be discussed in greater detail later. The mixed saliva froths
easily and is somewhat turbid, from admixture with epithelial
cells and some leucocytes, together with the mucin obtained
chiefly from the mucous glands of the mouth. The saliva
contains vast numbers of bacteria.2 The average specific
gravity is 1.003 to 1.004. The reaction is ordinarily stated
to be alkaline, but recent observations seem to indicate
that it is neutral, perhaps even acid, in reaction. That saliva
is able to neutralize strong acids does not indicate that this
secretion is alkaline in reaction, but simply that it contains
salts of strong bases combined with weak acids, such as car-
bonates and bicarbonates.

Toward litmus, lacmoid, and rosolic acid saliva reacts as
though it were alkaline. When phenolphthalein is used, how-
ever, the solution remains colorless. Ten cubic centimeters of
mixed saliva require 0.2 c.c. of a 1/10 normal alkali solution
before the phenolphthalein will just turn' pink, indicating an
alkaline reaction. Saliva is therefore to be considered as at
least neutral, if anything else, slightly acid, for phenolphthalein
is in this case to be looked upon as a more reliable indicator
than any of the others mentioned above. What holds for the

1 Vierordt*. Tabellen, Jena, 1888, p. 128.

2 See p. 160.

THE JUICES POURED OUT UPON THE FOOD. 65

ordinary mixed human saliva is true also of the saliva ob-
tained from the dog after stimulation of the chorda tympani
nerve or after poisoning with curare.1

Among the inorganic constituents of the saliva are the
chlorides, carbonates, bicarbonates, phosphates, and sul-
phates of sodium, potassium, magnesium, and calcium. The
escape of carbon dioxide from the saliva on standing allows
the precipitation of the bicarbonate of calcium as the car-
bonate. This substance is the chief constituent of salivary
calculi and "tartar."

Much importance was at one time attached to the quanti-
tative determination of the sulphocyanate in the saliva as
an indicator of the rate of protein metabolism, for it is gener-
ally believed that this substance is a product of protein me-
tabolism. Moore, however, believes that its estimation is of
little value.

The gases of the saliva are oxygen, nitrogen, and carbon
dioxide. The latter predominates, and is found chiefly in
chemical combination.

Among the organic constituents of the saliva the ferments
amylase and maltase are of the greatest importance. The
former of these two is characterized by its action upon starches
which are under its influence converted into maltose. Mal-
tase is especially effective in causing a still further cleavage
of this sugar into dextrose. While food is being chewed,
therefore, and for some time after it reaches the stomach, the
starches contained in it are undergoing a change which con-
verts them into substances readily absorbed by the alimentary
tract. The mucin contained in the saliva is probably of
little more than mechanical use in supplying food with a
coating which allows the more ready passage into and
through the oesophagus.

The oesophagus itself is studded with small mucous glands
which secrete a small amount of a ropy fluid rich in mucin.

1 See Munk: Centralblatt, fur Physiologie, 1902, XVI, p. 33.

66 PHYSIOLOGY OF ALIMENTATION.

The function of this secretion is, so far as known, purely
mechanical, in that it serves to lubricate the bolus of food as
it passes through this tube.

2. The Gastric Juice is the term applied to the secretion
of the mucosa of the stomach. Absolutely pure gastric juice
can be obtained from human beings only in small quan-
tities, impure juice in somewhat larger quantities. Pure
juice has been obtained in cases of gastric fistula. Most ob-
servations are based upon a study of the impure juice ob-
tained by feeding meals of known composition and then
evacuating the contents through a stomach-tube or a fistula
if such exists.

Pure gastric juice is best obtained from the dog by the
method of "sham feeding " of Pawlow and Schumow-Siman-
owsky.1 This consists in feeding a dog in which the oesoph-
agus has been separated in such a way from the stomach
that the food never really enters the stomach. When such
sham feeding is carried out, a reflex secretion of pure gastric
juice occurs. Such a sham feeding may be kept up without
injury to the dog for an hour daily, in the course of which
time 200 to 300 c.c. of juice may be collected. The quantity
secreted in twenty-four hours is subject to great variations,
but amounts to about 1/15 to 1/10 the body weight in dogs.
If we assume that the same proportion exists between the
amount of the gastric juice and the body weight in the case
of the human being, a man weighing 70 kilos would secrete
4 to 7 liters daily.

Konowaloff 2 describes the gastric juice obtained from the
dog by sham feeding as a clear, colorless, odorless liquid of a
specific gravity averaging 1.00478. The acidity given by
Konowaloff is higher than that of any other author, 0.544
percent of hydrochloric acid. A figure approximating this

1 See Chapter XI, Part 1. Pawlow and Schumow-Simanowsky:
Centralbl. f. Physiol., 1889, III, p. 113. Pawlow: Work of the
Digestive Glands. Trans, by Thompson, London, 1903, p. 12,

2 Pawlow: 1. c.

THE JUICES POURED OUT UPON THE FOOD. 07

value was obtained long ago by Hkideniiain. In spite of the
majority of observations to the contrary, this high acidity
probably represents the true value under physiological con-
ditions. Because of this acidity, bacteria do not develop
well in gastric juice, and it may in consequence be kept for
a long time without undergoing decomposition. The acidity
of the normal gastric juice is due to hydrochloric acid. This
was first proved by Prout and independently of him, but
later, by Tikdemann and Gmelin. The objections which
were raised against this idea by Claude Bernard and Ber-
reswil have been set aside by the researches of Schmidt.1
Traces of organic acids are at times found in the normal
gastric secretion.

Human gastric juice does not differ in its physical or
chemical properties from canine juice. The concentration
of the acid and the pepsin is perhaps somewhat lower in
man.

No complete analysis of gastric juice seems to be at hand.
Besides hydrochloric acid, gastric juice contains the fer-
ment acid- proteinase (pepsin), which has the power of acting
on proteins and splitting them into a number of simpler
bodies. Caseinase (rennin) is also found in the gastric
juice of the human being as well as that of other animals.
This ferment has the power of curdling milk. The hydro-
chloric acid present in the stomach is of itself able to
bring about this change, but the presence of the ferment
can be demonstrated by neutralizing the gastric juice
with an alkali, when it is found that the milk-curdling
power still persists. It is lost, however, when the neutral
gastric juice is heated to 70° C. for a short time. The
secretion of the stomach also contains a fat-splitting fer-
ment, lipase (steapsin), but its physiological importance
is probably small, as the ferment acts little or not at all

1 For an interesting account of the subject, see Mooke: Text-book of
Physiology, edited by Sciiai :i i.i; Kdinburgh, 1S(JS, 1, p. 351.

68 PHYSIOLOGY OF ALIMENTATION.

in an acid medium of the concentration found in the stomach.
A substance which is obtained as a coagulum from gastric
juice on boiling probably represents the combined ferments,
together with mucin and traces of organic material derived
from particles of digested food or the dead cells of the
stomach-wall itself.

The wall of the stomach contains the antiproteinase (anti-
pepsin) discovered by Weinland. As its name indicates,
this substance, when present, prevents the proteolytic fer-
ments from acting. As it is probably due to the presence
of this substance in the wall of the stomach, and in the in-
testines, that the alimentary tract does not digest itself, it
will be discussed in some detail later.1

The inorganic constituents of the gastric juice exclusive of
the hydrochloric acid consist of the chlorides and traces
of the phosphates of sodium, potassium, magnesium, cal-
cium, -iron, and ammonium. The only figures indicative
of the quantities in which these exist in the gastric juice
are based upon analyses of the impure secretion or such
as was obtained under other than physiological conditions.
As these are practically valueless, they will not be given
here.

The action of the ferments of the gastric juice, and the
variations in its composition and quantity, will be discussed
further on.

3. The Pancreatic Juice. — The quantity of juice which
flows from the pancreas varies greatly in different animals
and in the same animal under different physiological con-
ditions. The observations of the older investigators are
probably very incorrect. Pawlow and his coworkers state
that the amount of normal juice which can be obtained
from a dog possessing a permanent fistula2 is 21.8 c.c. per
kilo in twenty-four hours. The pancreatic juice from a
dog is a clear, colorless, odorless liquid, somewhat variable

1 See p. 133. 2 See Chapter XII, Part 1.

THE JUICES POURED OUT UPON THE FOOD. 60

in composition and often containing enough protein to
coagulate into a solid when heated.

The purest and apparently normal human pancreatic juice
has been obtained by Glaessner * from a forty-six year old
woman possessing a fistula of the pancreatic duct. Glaessner
describes it as a water-like liquid which froths easily and
on standing shows a very slight sediment. The juice has a
decided alkaline reaction even toward phenolphthalein, so
that it may really be regarded as alkaline in reaction.
Analysis of two specimens showed respectively 1.2708 and
1.2404 parts of dry substance in 100 of the juice. Analysis
of the dry substance showed, besides the ordinary inorganic
salts, albumin, albumose, and peptone. Glaessner gives as
the specific gravity of the juice 1.00748.

The quantity of juice secreted by Glaessner 's patient in
twenty-four hours varied from day to day, the extremes
being 420 and 848 c.c. The quantity as well as the quality
varied with the character of the food ingested. During
starvation the quantity was very low, as was also the
digestive power for proteins, fats, and starch. Under
these conditions the alkalinity was also lower than after
feeding.2

The pancreatic juice contains several ferments — alkali-
proteinase (trypsin), lipase (steapsin), amylase (amylopsin),
caseinase (rennin), and at certain times lactase. The alkali-
proteinase is able to act upon proteins and to split them
into a series of simpler substances in a manner similar to
but more powerful than acid-proteinase. Lipase acts upon
fats, breaking these up into fatty acid and alcohol. The
amylase of the pancreas is similar to that of the saliva, and
through its action on starch brings about the formation

1 Glaessnek. Zeitschrift fur physiologische Chemie, 1904, XL, p. 465.
For a review of the older literature on human pancreatic juice, see
Schumm: Zeitschrift fur physiologische Chemie, 1901.', XXXYl , p, 292,

70 PHYSIOLOGY OF ALIMENTATION.

of maltose and dextrin. Caseinase is the name given to
the milk-curdling ferment of the pancreas. It is similar
to the milk-curdling ferment of the stomach. Lactase is
present in the pancreas only at certain periods in the life
of an animal and under certain conditions. It is found
normally in the pancreatic secretions of the puppy during
the period of lactation. In adult dogs it is absent, but it
can be made to appear again if the dog is kept for some
time on a milk diet or any diet containing milk-sugar. This
ferment has the power of acting upon milk-sugar (lactose)
and converting it into dextrose and galactose. A detailed
discussion of these ferments is given further on.1

It is as yet not entirely settled whether the ferments are
secreted as such from the pancreas or as proferments. Ac-
cording to Delezenne, Frouin, and Popielski,2 the juice as
collected directly from the pancreatic duct never contains
alkali-pro teinase (trypsin), but only its proferment (tryp-
sinogen). This yields alkali-pro teinase, however, as soon as
it flows over the mucous membrane of the duodenum, where
it encounters enterokinase.3 Whether similar conditions hold
for the other ferments is a matter of dispute.

In human pancreatic juice Glaessner could find no alkali-
proteinase (trypsin), but only the proferment, which could,
however, be converted into alkali-proteinase by adding to
it an extract (enterokinase) of the mucous membrane of the
small intestine obtained from human corpses. Both lipase
and amylase were also found, but no maltase, sucrase, or
lactase, a fact which agrees well with experimental findings
in animals.

4. The Bile is the name given to the secretion from the
liver which is poured into the duodenum through the com-

1 See Chapters IV, V, VI, VII, and VIII.

2 Delezenne and Frouin. Comptes rendus de l'acad., CXXXIV, p.
1526; Comptes rendus de Soc. biol., LlV, p. 691; Popielski. Central-
blatt fur Physiologie, XVII, p. 65.

3 See Chapter XIII, Part 4.

THE JUICER POURED OUT UPON THE FOOD 71

mon duct. The quantity of bile secreted in twenty-four
hours varies not only in different animals but in the same
animal under different circumstances. Contrary to the
generally accepted view, the secretion of bile is nol con-
tinuous and of varying intensity, that is to say, remittent,
but intermittent. During certain periods no bile whatsoever
escapes into the intestine. According to von Wittich and
Westphalen, the total amount of bile secreted by a human
being in twenty-four hours is about 500 c.c.1 These obser-
vations were made on two men having biliary fistula). The
specific gravity of the bile is, according to Westphalen,
1.0104. In 100 parts of liquid bile are contained 2.253
parts of solids.

All these figures must be looked upon as only approxi-
mately correct. Later,2 when the quantitative and quali-
tative variations in the secretion of the bile are discussed,
the reason for this will be more apparent. This explains
also why the figures of scarcely any two of the score of
observers who have worked on the biliary secretion
agree.

The bile consists of the secretions of the liver-cells them-
selves, mixed with the mucus which is secreted by the bile-
channels and the gall-bladder. As the bile passes from the
liver-cells toward the intestine it undergoes a change, the
bile from the gall-bladder and lower bile-passages being
somewhat more viscid, because of loss of water and ad-
mixture with mucus, and cloudier, because of the presence
of cells and cellular debris, than that collected from the bile-
passages higher up. The color of the bile is different in
different animals, and in the same animal, depending upon
the conditions under which it has been obtained. Human
bile obtained immediately alter death has a golden-yellow,
brownish-yellow, or at times slightly greenish color. That

* Viekoudt: Tabellcn, Jena, 188S, p. 135.
*See Chapter XIII, I 'art 1.

72 PHYSIOLOGY OF ALIMENTATION.

obtained at an ordinary post-mortem is yellowish brown,
brown, or green. The reaction of the bile is ordinarily
stated to be alkaline. It is probable, however, that it is
neutral.

The most important constituents of the bile besides water
are the bile acids in combination with the alkali metals, and
the bile pigments. Among the other important constituents
are the inorganic salts which are universally present in the
body and fats, lecithin, cholesterin, urea, and soaps.

The bile acids are several in number and are usually divided
into the glycocholic and taurocholic groups, each of which has
several members. The bile pigments are also several in num-
ber. The reddish-yellow bilirubin and the green biliverdm
are always present in bile under physiological conditions.
Hydrobilirubin perhaps also belongs to this group. Under
pathological conditions, as in gall-stones, a number of other
pigments besides those already mentioned may be found,
of which choletelin, bilifuscin, biliprosin, bilihumin, and
bilicyanin are the most important. Bilirubin and hydro-
bilirubin are of great physiological interest because of the
identity or at least close chemical relation of the former to
a derivative of haemoglobin, hsematoidin, and of the latter to
urobilin, one of the urinary pigments.

The inorganic constituents of the bile comprise the chlo-
rides, phosphates, and sulphates of sodium, potassium, cal-
cium, magnesium, iron, and copper. Urea is found only in
traces. The following three analyses of human bile by
Hammarsten,1 which probably are as trustworthy as any at
our disposal, will give an idea of the relative proportions in
which the various constituents exist in this secretion. The
figures indicate parts per 1000.

Water 974.800 964.740 974.600

Solids 25.200 35.260 25.400

i Hammarsten: Text-book of Physiological Chemistry. Translated
by Mandel, New York, 1904, p. 276.

THE JUICES POURED OUT UPON THE FOOD 73

The latter consist of:

Mucin and pigments 5.290 4.290 5.150

Taurodiolate salts 3.034 2.079 2.180

Glycocholatc salts 6.276 10.161 6.S60

Fatty acids from soaps. ... 1 . 230 1 . 300 1.010

Cholestcrin 0.630 1.600 1.500

Lecit hin \ / 0 17". 0 . 650

Fat J 10.956 0 610

Soluble mineral salts 8.070 6.760 7.250

Insoluble mineral salts 0 . 250 0 . 490 0 210

The functions of the bile and the regulation of the biliary
flow can be better discussed elsewhere.1

5. The Intestinal Juice. — Under this heading are grouped
all the secretions of the intestine proper from the pylorus
of the stomach to the anus. The intestinal juice has been
obtained in man from cases of intestinal fistula; from animals
it is obtained experimentally and unmixed with other diges-
tive secretions or food by the production of either a Thiry
or a Vella fistula in any desired portion of the small or large
intestine.2

The pure juice obtained from different portions of the
intestinal canal below the stomach varies not only in amount
but also in composition. We shall first consider the secre-
tion of the small intestine (succus entericus). Rohmann3
describes the juice 0} the small intestine of the dog as scant}'
in amount, viscid, and somewhat gelatinous in the upper
portions, and as larger in amount and more fluid in the lower
portions. Thiry 4 obtained a maximum secretion of 4 c.c-
per hour from a loop of small intestine having a total sur-
face of 30 sq. cm. The specific gravity is given by the
same author as 1.0115, and the juice is described as clear,
light yellow, somewhat opalescent, and of a decided alka-
line reaction. The juice from the small intestine contains

1 See Chapter XIII, Parts I and 2.

1 See Chapter XIII, Pari 3.

8 Rohmann. Pfluger's Archiv, 1887, XL1, p. 424.

4 Thiry. Vieroult's TaKcllen, Jena, 1S88, p. 140.

74 PHYSIOLOGY OF ALIMENTATION.

protein, mucin, urea, and the ordinary salts found every-
where in the secretions and tissues of the body. The amount
of carbonate is particularly high, to which fact the alkaline
reaction of the juice is attributed.

The descriptions given of the secretion of the small in-
testine in the human being are practically the same as those
given above for the juice obtained from dogs. The best
observations on human intestinal juice are those of Tubby
and Manning,1 Hamburger and Hekma,2 and Nagano.3 In
Tubby and Manning's case pure intestinal juice was obtained
from a piece of intestine 3 J inches long situated some 8 inches
above the ileocsecal valve. Their description of the juice
is similar to that of other observers and may be taken as a
type. The daily yield of juice from this piece of intestine
varied from 19 to 35 c.c; the specific gravity from 1.0016
to 1.0162, on the average 1.0069. The fluid was opalescent,
and on standing a sediment consisting of leucocytes and
desquamated intestinal epithelium formed. The juice gave
a strong alkaline reaction, and contained protein, mucin,
and the ordinary salts, of which the carbonates and chlo-
rides of sodium and potassium were the more conspicuous.

Within the last few years our conceptions of the nature
of the chemical substances contained in the secretions of
the intestine and in the walls of this portion of the alimentary
tract have undergone great revision, and from having looked
upon this chapter of alimentation as comparatively unim-
portant we now rank it with chapters on the pancreas and
stomach. This is due to the discovery in the intestinal
juice and in the walls of the intestine of a number of new
chemical substances, an understanding of the functions of
which, together with a proper appreciation of the physio-

' Tubby and Manning: Guy's Hospital Reports, London, 1891,
XLVIII P- 277.

- Hamburger and Hekma- Journal de Physiol., IV. p 805.

'Nagano: Mittheilungen aus den Grenzgebieten der Medicin und
Chirurgie. IX, p. 393.

THE JUICES POURED 01 T UPON THE FOOD 75

logical importance of (hose already well known, has given us
a new insight into the importance of the small intestine in
the great problem of alimentation. The following is a list
of these chemical substances, together with a brief indication
of their physiological functions, which are discussed in grea ter
detail later.

Proteinase. This ferment is found in the secretion and
mucous membrane of the duodenum and originates from
the glands of Brunner, found in this section of the intestine.
It seems to be identical with the acid-proteinase of the
stomach, as it acts best in an acid medium. It is evident
that some opportunity is given this ferment to aid in the
digestion of proteins. But as compared with the activity of
the stomach, or pancreas, that of the duodenum is probably
only small.

Protease (erepsin) is one of the most important ferments
found in the intestinal juice. This ferment, discovered by
Cohxiieim, has no action upon "native" proteins except
casein, but has the power of splitting proteoses and pep-
tones into a number of simpler substances (mono- and
diamino acids, ammonia, etc.) which are similar to those
formed through the action of either acid- or alkali-pro-
teinase on proteins. Protease must therefore not be con-
founded with the proteolytic ferments of either the stomach
or pancreas. The presence of this ferment, in human in-
testinal juice has been proved by Hamburger and Hekma.

Lipase (steapsin). It is ordinarily stated that lipase does
not occur in the intestinal juice or in the mucosa. The
experiments of Kastle and Loevenhart indicate, however,
that it is found in all portions of the mucosa of the small
intestine in sufficient amounts to be of the greatest impor-
tance in the absorption of fats. The lipase of the intestine
is identical with that of the pancreas and pancreatic juice,
and, like the latter, splits fats into fatty acid and alcohol.

Ami/last is t'.umd in the small intestine and is secreted
in sufficient amounts to play an important role in the absorp-

76 PHYSIOLOGY OF ALIMENTATION.

tion of starches. The ferment splits starches into malt-
ose and dextrin. Its presence in human intestinal juice
has been proved by Nagano, Hamburger and Hekma.

Maltase. The occurrence of this enzyme in the small
intestine is still questioned. Evidence is slowly accumu-
lating, however, to show that it is to the presence of this
enzyme in the intestinal juice and the intestinal mucosa
that we owe the splitting of the maltose formed from starch
into the dextrose found in the intestine after the ingestion
of starch or malt-sugar. The presence of a maltose-splitting
ferment in human intestinal juice is indicated by the re-
searches of Nagano, Hamburger and Hekma.

Sucrase (invertase, invertin) is one of the most important
enzymes found in the secretion of the small intestine. Cane-
sugar, which serves as such a common article of diet, would
without the presence of this enzyme be scarcely absorbed by
the intestine. The sucrase splits the cane-sugar into the
readily absorbable dextrose and lssvulose.

Lactase is found in the intestinal tract of infants and those
adults who consume milk-sugar either as a separate article
of diet or as one of the constituents of milk. Lactase acts
upon milk-sugar (lactose) and splits this into dextrose and
galactose.

Arginase is a ferment which has recently been discovered
by Kossel and Dakin. It has the interesting property of
splitting arginin into the two chemically much simpler sub-
stances ornithin and urea. It is a ferment which occurs not
only in the mucous membrane of the intestine, but also in a
number of the parenchymatous organs.

Antiproteinase (antipepsin and antitrypsin). This sub-
stance is found in the mucosa of the intestine, but not in the
secretions of the intestine. Like the antiproteinase of the
stomach, it has the power of preventing the proteinases from
acting upon proteins and splitting them into their well-known
decomposition-products.

Enterokinase. The ferment character of this substance

THE JUICES POURED OUT UPON THE FOOD. 77

has not as yet been entirely established. It is the name
given by Pawlow to a substance, discovered by Chepo-
WALNIKOW in the mucous membrane and secretions of the
small intestine, which has the power of converting the
inactive proferment of the pancreas into the active alkali-
proteinase (trypsin). Hamburger and Hekma have found
this substance in human intestinal juice.

Pancreatic Secretin is in no sense a ferment. It is a term
applied by Bayliss and Starling to a substance formed in the
upper portion of the intestine during digestion, which is
absorbed into the blood and, reaching the pancreas, increases
the secretion from this gland.1

The secretion of the large intestine has been studied in the
human being in cases of fistula opening into the ascending,
transverse, or descending portions of this part of the intestinal
tract, and in animals in which artificial fistulae have been
created. The observations of all who have worked on the
secretion of the large intestine agree in stating that it is small
in amount and mainly composed of mucus. The juice is
alkaline in reaction and seems to contain no enzymes of
digestive importance. It is probable, however, that the food
which escapes through the ileocecal valve, mixed with the
enzymes poured out upon it higher up in the alimentary canal,
continues to undergo digestive change in the large bowel. Of
greatest importance is the absorption which occurs in the
various portions of the colon. While the food is soft in con-
sistency in the ascending portion of the large intestine, it
becomes less liquid and finally firm as the transverse and
descending portions are reached, until in the rectum the solid
faces are formed.

While no enzymes derived from the large intestine itself act
upon the food in the colon, enzymes derived from the bacteria
present here bring about most profound changes in the food.

1 The ferments are considered in greater detail in the succeeding
chapters. Enterokinase is discussed in Chapter XHI, Pari 1. pan-
creatic secretin in Chapter XII, I'art ■'<.

78 PHYSIOLOGY OP ALIMENTATION.

These are chiefly of a putrefactive character, and affect in the
main the protein constituents of the food. Certain of the
bacterial enzymes belong to the proteinase group, and these
split the undigested protein remnants into leucin, tyrosin, and
the other products of proteinase digestion. Indol, skatol,
and various phenols are produced also, as well as fatty acids
(lactic, butyric, caproic, etc.) and gases (hydrogen, hydrogen
sulphide, and methane).

CHAPTER IV.
FERMENTS AND FERMENTATION.

I. Organic Ferments. — Since ferments, the activities of
which we recognize in so many physiological processes, play a
great role in that special chapter of physiology with which
these pages deal, namely, alimentation, it may not be amiss
to discuss here their general properties.

Ferments represent only a special class of the so-called
catalytic agents, and are in consequence distinguished by the
same characteristics as catalyzers in general. A catalyzer is
any substance which, without appearing in the end-products of a
chemical reaction, alters by its mere presence the rate of this
chemical reaction. The catalytic agent is therefore not to be
looked upon as the cause of the chemical reaction, for this
occurs even in the absence of the catalyzer, only then at a dif-
ferent rate.1 When a catalytic agent increases the velocity of
a chemical reaction it is said to be a positive catalyzer; on the
other hand, when it decreases the rate of a chemical reaction
it is known as a negative catalyzer. Examples of positive cata-
lyzers will occur to everyone. Common ones from inorganic
chemistry are manganese dioxide, which hastens the de-
composition of potassium chlorate into potassium chloride
and oxygen when heated; and nitrogen tetroxide, which
accelerates the oxidation of sulphurous acid into sulphuric in
the manufacture of the latter substance. In both instances

'Ostwald: liber Kataly.se, Leipzig, 1902, p. 12. Cohen: Physical
Chemistry for Physicians. Translated by Martin H. Fischer, New
York, 1903, p. 35.

79

80 PHYSIOLOGY OF ALIMENTATION.

the catalyzers do not appear in the end-products, and may,
when the reaction has been brought to a standstill, be recov-
ered in an unaltered state. As is well known, the decompo-
sition of potassium chlorate and the oxidation of sulphurous
acid occur even when the catalytic agents are not present,
but much more slowly.

Any of the ferments may be cited as examples of organic
catalyzers. We may mention here lipase, which hastens the
chemical decomposition of fat into fatty acid and alcohol,
and proteinase, which accelerates the rate of decomposition
of proteins into simpler substances. Here also we deal with
chemical reactions which take place even when no ferments
are present. Under such circumstances the decompositions
occur very slowly, however, requiring weeks, months, or
years to attain the degree of decomposition which in the
presence of the respective ferments may be reached in a
few hours. As was found to be the case with inorganic
catalyzers, so here also we find that the ferments do not
appear in the end-products of the reactions which they
catalyze.

Examples of negative catalyzers are much more difficult
to discover. Only isolated ones have been described, and
since nearly all of them seem now to be regarded as inhibitors
of positive catalyzers, they will not be discussed here. Nega-
tive organic catalyzers are entirely unknown, unless we look
upon the antiferments as belonging to this group. Whether
they do or not must be left undecided until the mode of action
of the antiferments has been discovered. These substances
decrease markedly the velocity of certain chemical reactions
occurring in the presence of a ferment. Until we know whether
the antiferment produces its effects by combining with the
ferment (either chemically or mechanically) or by decreasing
directly the velocity of the chemical reaction, the classifica-
tion cannot be made. Only in case the latter of these two
possibilities were proved to be the correct one could we
look upon the antiferments as negative catalyzers.

FERMENTS AND FERMENTATION. 81

The catalytic agents produced in living cells or tissues are
called ferments. They are usually divided into two groups,
the so-called organized and u?iorga?iizcd ferments. The first
term is applied to those ferments which are connected in some
way with the life of the cells in which they are produced,
and which cannot be extracted from these cells. The un-
organized ferments can, on the other hand, be extracted
from the cells in which they are formed, and are able to
produce their characteristic actions outside of the cells as
well. The unorganized ferments are also known as enzymes
(Kuhne). To the latter class belong all the digestive ferments,
amylase, maltase, acid- and alkali-proteinase, etc., which
it has been possible to extract from the tissues or secretions
of the alimentary tract, and which produce their characteristic
reactions in a test-tube as well as in the living intestinal
tract. To the class of organized ferments belong all those
whose presence we recognize only by their chemical be-
havior and whose activities continue only as long as the
cell in which they were produced is intact. Many of the
"vital" activities of tissues have to be attributed to such
organized ferments. It is useless to enumerate the organized
ferments, because the list of unorganized ferments (enzymes)
is constantly growing at the expense of the organized, and we
may hope in time to speak of enzymes alone. To illustrate,
we need only cite Buchner's successful extraction of zymase
from the yeast-cell, which is able to bring about the decom-
position of glucose into alcohol and carbon dioxide quite as
readily as the yeast-cell itself. The discovery of Buchner is
mentioned in this connection because it takes away one of
the pillars which for decades have been utilized to support
the idea of the essential difference between organized and un-
organized ferments. In the pages which follow the terms
ferment and enzyme are used synonymously.

The number of known ferments is already very large, and
is being added to daily. It is unfortunate that a uniform
system of nomenclature has not yet been adopted by all the

82 PHYSIOLOGY OF ALIMENTATION.

workers in this field. Persistence in the use of old methods
of naming even newly discovered enzymes, and the existence
of the same ferment under different names, are extremely
confusing. The best method of naming ferments to-day
is to add the ending ase to the root of the Latin or Greek name
of the substance upon which the ferment acts. Thus maltase
acts on maltose, sucrase on sucrose, tyrosinase on tyrosin,
amylase on starch, etc. Since the action of many, probably
all, ferments is reversible (as will be explained later), and as
in this way several names might be given to one and the
same ferment, it should be the rule to add the ending ase
to the root of the chemically more complex substance upon
which the ferment acts. The ferment which accelerates the
decomposition of sucrose into " invert-sugar " is therefore
better named sucrase than invertase, for sucrose is chem-
ically more complex than the dextrose or the lsevulose which
constitute the invert-sugar. It is sometimes convenient to
add the ending ase to the Latin or Greek root of a word express-
ive of some striking characteristic of a group of ferments.
Under the oxidases, for instance, are classed a large number
of individual enzymes, all of which have the power of catalyz-
ing the oxidation of various chemical substances. But there
are many specific oxidases, and these are regrouped under
the general heading, according to the substance or sub-
stances with the oxidation of which they are particularly
concerned, as tyrosinase, laccase, olease, etc.

Sometimes ferments having the same specific activity
show differences in their behavior toward altered external
conditions. For example, the lipase (steapsin) obtained
from the pancreas does not behave in exactly the same way
toward changes in temperature and concentration, toward
acids, alkalies, etc., as the lipase obtained from certain vege-
table cells. This has aroused the suspicion that they may not
all be identical. For this reason ferments are often spoken
of in the plural, as lipases, meaning thereby fat-splitting
enzymes derived from any source.

FERMENTS AND FERMENTATION. W

We arc only jusi beginning to gel some idea of I be chemical
composition of a few of the simpler ferments. For this
reason the recognition of the existence of a ferment within
a cell or out of it is Still dependent, not upon the recognition
of the chemical substance itself, but rather upon the dis-
covery of certain properties common to all ferments and
specific ones characteristic of separate enzymes. The fol-
lowing are usually looked upon as properties common to all
ferments, and the first four are utilized in proving the existence
of a ferment in cells or tissues, or in extracts made of these.

(a) A ferment does not initiate a chemical reaction but only
alters its velocity. The ferment acts essentially through con-
tact, in that its mere presence is responsible for the altered
velocity of the catalyzed reaction. At the end of the reaction
the ferment is (under ordinary circumstances) found in an
unaltered state in the reaction mixture. The ferment does
not, therefore, enter into the end-products of the reaction.
When hydrochloric acid is poured upon sodium carbonate in
order to decompose it, we have at the end of the reaction the
chlorine of the hydrochloric acid appearing in the sodium
chloride, and the hydrogen in the carbonic acid. Not so, how-
ever, in the case of a ferment. When sucrase (invertase,
invertin) acts upon cane-sugar, dextrose and laevulose are
formed, but neither of these products contains in chemical
combination any part or all of the sucrase molecule, — the
sucrase is found in an unaltered condition at the end of the
reaction.

It is possible that the molecules of the ferment enter tem-
porarily into chemical combination with the substance acted
upon or with its products. This assumption is made on the
ground that in' some simple catalytic processes the catalyzer
does temporarily combine with the reacting substances. This
is t he case, for example, in the manufacture of sulphuric acid,
in which steam, sulphur dioxide, oxygen, and nitrogen dioxide
are introduced simultaneously into a large chamber. In
brief, it is believed that the sulphur dioxide and steam com-

84 PHYSIOLOGY OF ALIMENTATION.

bine to form sulphurous acid, which is oxidized to sulphuric
by the nitrogen tetroxide formed through the union of the
nitrogen dioxide with oxygen. The nitrogen dioxide, which
plays the role of a catalyzer in this reaction, unites first of all
with oxygen to form nitrogen tetroxide, but the nitrogen
dioxide is restored immediately in that the sulphurous acid
takes away the oxygen from the nitrogen tetroxide. The
nitrogen dioxide acts, therefore, only through its mere pres-
ence, appearing in an unaltered state at the end of the reac-
tion. Nor does it initiate a chemical reaction, for the oxida-
tion to sulphuric acid occurs whenever sulphurous acid is
exposed to oxygen. But the reaction, which under these
circumstances occurs only very slowly, occurs very rapidly
when nitrogen dioxide is present.

There are other facts, into a discussion of which we cannot
go here, that speak against this conception of the action of a
ferment, and seem to indicate that certain physical charac-
teristics of the ferment (or, in general, any catalytic agent),
such as its surface, electrical condition, etc., constitute the
real cause of its peculiar action. However this problem may
ultimately be settled, the fact seems fairly well established
that, except for a simple decomposition which is to be dis-
cussed later, the ferment appears in an unaltered state at the
end of the reaction.

(6) In infinite time the amount of chemical change brought
about by a ferment is independent of the concentration of the
ferment. This means that a small amount of a ferment will
bring about as much chemical change as a larger one, pro-
vided unlimited time is given. In this regard, therefore, a
ferment differs from the ordinary constituent of a reaction
mixture. We know from the law of chemical mass-action of
Guldberg and Waage that in any ordinary chemical reaction
the amount of the chemical change is proportional to the
concentration of the reacting substances. This does not hold
in the case of ferments, where the amount of ferment is in
nearly all cases exceedingly small when compared with the

FERMENTS AND FERMENTATION. 85

amount of substance acted upon. This fact alone speaks
against any idea that fermentation is dependent upon a
quantitative chemical decomposition between catalyzer and
catalyzed substance — that, in other words, we are dealing
with a stoichiometrical reaction.

It is well to note that what has been said holds true only
when infinite time is allowed. For shorter periods — which
vary with the nature of the catalyzer and the nature of the
substance or substances catalyzed — the degree of fermentation
is clearly and often definitely a function of the concentration of
the ferment. We cannot here enter into a discussion of the
influence of the concentration of a ferment upon the velocity
of the fermentation. In general it can be said that only
within exceedingly narrow limits of time and concentration,
both of the substances undergoing catalysis and the catalyzer,
is the rate of fermentation approximately directly propor-
tional to the concentration of the ferment. In the majority
of instances the variation is very great, and an increase in the
concentration of the ferment is not followed by a correspond-
ing increase in the rate of the fermentation. Thus doubling
the concentration of a ferment in a certain reaction mixture
does not multiply the rate of the catalysis by two, but by less
than two.

The reason why the rate of catalysis is not proportional
to the amount of ferment added is not yet entirely clear.
It seems to be dependent, in part at least, upon a decom-
position which the ferment itself suffers, in consequence of
which its concentration is steadily decreased. More potent
than thia seems to be the accumulation of the products of
the fermentation. The opinion has been expressed that
the accumulation of the products of the catalyzed reaction
injures the ferment, but this view can no longer be held,
since we have learned that the activity of many enzymes
is reversible. For example, in the action of maltase on
maltose and the production of dextrose we might assume

86 PHYSIOLOGY OF ALIMENTATION.

that the ever-increasing amount of glucose in the reaction
mixture interferes with the further action of the maltase.
The argument falls to the ground, however, when we deal
with the action of maltase on glucose and the production
of maltose. If glucose interfered with the action of the
enzyme, the velocity of this reaction ought to be lowest
at first and increase as more and more maltose is produced.
As an actual matter of fact, the opposite occurs, and the
velocity of the reaction becomes progressively less as the
maltose accumulates. In either case, therefore, the accu-
mulation of the fermentation-products seems to interfere
with the chemical reaction itself.

(c) Ferments are usually characterized by a great sensi-
tiveness to comparatively low temperatures. In fact, it is one
of the commonest means employed in proving that a cer-
tain chemical reaction is dependent upon the presence of a
ferment, to heat the reaction mixture to boiling and find
that after this treatment the reaction no longer takes place.
(In most instances the reaction does in reality still occur,
only so infinitely slowly, as a general thing, that it is unrecog-
nizable by the analytical methods at our disposal.) This
means that a temperature of 100° C. destroys the activity
of the ferment. Some few ferments are able to endure
this temperature or even a higher one for a short time, but
the vast majority cannot stand heating to even 60° C. for
any length of time. The cause of this inactivation of the
ferment is to be sought in a decomposition which it under-
goes. The nature of this decomposition is not as yet under-
stood. Ferments are not nearly so sensitive to tempera-
ture in the dry state as in the moist. Many ferments which
are readily destroyed by heating to 60° C. for some minutes
in the presence of water withstand a temperature of 120° C.
for much longer periods if the ferments are thoroughly
dry. An every-day illustration of this is found in the well*
known fact that in surgical sterilization the death of all
bacteria and spores is obtained much more easily by the

FERMENTS AND FERMENTATION. $t

use of moist heat than dry heat. These facts seem to indi-
cate that the decomposition of the ferment is accompli
through the taking up of water— in other words, that we
are dealing with a hydrolysis of the ferment. The pos-
sibility of a mere change in the physical stale ol the fer-
ment as the cause of its inactivation through heat must,
however, also be considered, for there are many reasons at
hand for believing that ferments owe their specific virtues
quite as much to their physical state of aggregation as to
their chemical make-up.

The fact that ferments suffer a decomposition when
exposed to higher temperatures explains the peculiar be-
havior of chemical reactions which are being catalyzed
by ferments when the reaction mixtures are exposed to
various temperatures. As is well known, the velocity of
ordinary chemical reactions varies greatly with different
temperatures. An every-day illustration of this fact is
found in the use of heat to hasten chemical decomposi-
tion in our ordinary analytical reactions, and the resort to
refrigeration in the effort to delay decomposition in animal
and vegetable matter. For ordinary chemical reactions it
has been found that the reaction velocity is, roughly speak-
ing, doubled or trebled for every increase of 10° C. in tem-
perature.1 When we are dealing with chemical reactions
which are taking place under the influence of a ferment,
things are entirely different. Within certain limits we
have here also an increase in reaction velocity with an in-
crease in temperature, but when a certain point is reached —
which varies with different ferments, and with the same
ferment acting in different media — the reaction velocity
no longer increases but decreases with a further elevation
of the temperature. Finally a point is reached at which
the reaction ceases entirely (apparently). It is for this

1 Cohen: Physical Chemistry for Physicians. Translated by Mai-hx
11. Fischer, New York, 1903, p. 53.

88 PHYSIOLOGY OF ALIMENTATION.

reason that an optimum temperature exists in the case of
all ferments. By this is meant the temperature at which
the particular ferment under the given conditions brings
about its characteristic effects most rapidly — that is to say,
its reaction velocity is greatest. This optimum tempera-
ture lies, for most ferments, close to 40° C.

The reason for the existence of such a maximal reaction
velocity can be readily understood from what has been
said before. If the ferment remained unchanged upon
heating a reaction mixture, the velocity of the chemical
reaction would increase progressively with an increase in
temperature, just as in any ordinary reaction mixture. When,
however, we are dealing with reactions in which ferments
are concerned, the ferment is all the time undergoing a
decomposition itself, and the rate of this decomposition is
also a function of the temperature. It is known, in general,
that the length of time required to destroy a ferment at a
comparatively low temperature is greatly reduced by an
elevation of only a few degrees centigrade. Tammann, who
has worked out the velocity of the decomposition of the
ferment synaptase (emulsin) above 60° C, finds that an
increase in temperature of 10° C. multiplies the decom-
position velocity of the ferment by more than seven. In a
reaction mixture in which a ferment is concerned we have
therefore at least two reactions going on side by side, and
it is the product of these two simultaneously occurring
reactions which is represented by a curve that attains a
maximum at one point. Since the two reactions which yield
this curve have their individual characteristics, it can be
readily understood why the curves not only of different
enzymes, but even of the same enzyme acting under different
external conditions, must vary. In Fig. 18 are shown the
curves representing graphically the changing reaction veloc-
ities of various ferments with variations in the temperature.
Curves 1, 2, 3, and 4 illustrate the behavior of indigo enzyme
obtained from various sources; carve 5 that of synaptase

FERMENTS AND I- Eli MENTATION.

v..

(emulsin) obtained from sweet almonds. The curves show
very well a region in which an increase in temperature is
followed by an increase in the rate of chemical reaction, the
attainment of an optimum, and the rapid fall to the base-
line, with only a slight further increase in the temperature
beyond the optimum. In general, it may be said that all
ferments behave in a similar manner.1

V/

7

3^-

\

^^

5

\

>-^~

II

10

80

90

20 30 -JO 50 60 70

TEMPERATURE IN DEGREES CENTIGRADE

Fig. IS.

(Copied from Cohen: Physical Chemistry for Physicians. Trans, by

Fischer, New York, 1903, p. 56.)

(d) The reactions which are catalyzed by a ferrm nt are
rarely, if ever, complete unless the products of the reaction arc
removed as soon as formed. By this is meant that if a certain
substance and a ferment capable of acting upon this sub-
stance are mixed together, say in a test-tube, not all of the
substance will bo acted upon by the ferment, but when the

1 Cohen: Physical Chemistry for Physicians. Translated by Martin
H. Fischer, New York, L903, p. 55.

90 PHYSIOLOGY OF ALIMENTATION.

reaction has come to a standstill a certain amount of the
substance will be found unchanged in the reaction mixture.
If, for example, a certain amount of fat and lipase (steapsin)
are mixed together and the whole is allowed to stand until
the reaction has come to a standstill, it is found that some
of the fat has been left in an undigested state. What has
been said of fat holds true also for a large number of other
ferments — in fact, all that have thus far been investigated.

It is only recently that an explanation of this interesting
and fundamental fact has been given, and, as will become
apparent later, a large number of physiological processes
rendered more intelligible in consequence. It used to be
said that the products of the fermentation interfered with
its further progress. We know now, however, that the reason
for the incompleteness of the chemical reaction lies in the
fact that the ferment is continually re-forming from the
products of the reaction the substance or substances with which
the ferment was mixed originally. Thus, in the case of fat,
which is split into fatty acid and alcohol by lipase, we
have two reactions going on side by side: first, the long-
recognized analytical one, by which fatty acid and alcohol
are formed from the fat; and, second, a synthetical one, by
which fat is formed from the fatty acid and alcohol. Both
reactions are catalyzed by the same ferment, the action of
which we say is reversible. This reversibility of the action of
a ferment is another of its fundamental characteristics. Whether
in any given case a ferment acts synthetically or analytically,
it will be shown later, is determined solely by the ordinary
laws of chemical equilibrium.

If the products of a chemical reaction which is being catalyzed
by a ferment are removed as soon as formed, the reaction
will be completed. If, in the illustration cited above, the
fat and lipase are put, not into a test-tube, but into a parch-
ment bag suspended in a current of water, all the fat will
be split into fatty acid and alcohol. Under these circum-
stances the fatty acid and alcohol diffuse through the parch-

FERMENTS AND FERMENTATION. 91

merit wall as soon as formed and are carried off by the
stream of water. The products cannot therefore accumulate

and be synthesized into fat. In this way all the fat is
ultimately split into fatty acid and alcohol.

(r) For reasons which arc at present not well under-
stood, the fermentative activity of extracts of organs or the isolated
ferments of the alimentary secretions is disappointingly low
irli en compared tvith the activity of the uninjured organ or the
freshly oldained secretion. The fact that all the ferments
1 1 his far studied are apparently colloidal in character, and
consequently exceedingly sensitive to changes in their sur-
roundings, is perhaps responsible for this, at least in part.
Some very active preparations of ferments have, however,
been described. The most active are, no doubt, the prepara-
tions of amylase prepared by Weinland.1 The following two
experiments, taken from his note-books, may serve as illus-
trations.

(a) Forty-one grams of the mixed pancreas from three pigs
are ground up for ten minutes in a mortar with 41 grams of
quartz sand. To the mixture are added 21 grams of infusorial
earth, and the whole is ground for another ten minutes. A
paste results. This paste is placed in a cloth and subjected to
the pressure of a Btjchxer press. Only 7 c.c. of juice (1) are
obtained. On the following day the paste is mixed with
30 c.c. of 0.9 percent NaCl solution and 10 c.c. of disodium
phosphate solution. This gives a somewhat thin mixture.
This is again put under the press and 29 c.c. of juice are ob-
tained, to which are added the 7 c.c. (1) obtained before. A
third pressing raises the entire amount of extract to 43 c.c.
(in other words, about the volume of the original amount of
pancreas). The extract is filtered, when a clear, yellowish
solution results, and this is covered with toluol to prevent
the development of bacteria. Five days later 5 c.c. iA' a two-
percent glycogen solution (upon which amylase acts :is readily
as upon starch) are mixed at room temperature with a little

KI-I solution, when the whole assumes a dark-red color.

indicating the presence of the glycogen. To this mixture there
1 Wkixi wi>: Personally communicated.

92 PHYSIOLOGY OF ALIMENTATION.

is added 0.1 c.c. of the extract prepared above. In one
minute the glycogen solution has lost its color, and the Trommer
test results positively. The paste from which the extract has
been obtained fails to remove the color from a similarly pre-
pared mixture of glycogen and iodine, even when several
minutes are allowed.

(/?) By methods similar to those described above, 60 c.c.
of juice are obtained from 59.4 grams of dogs' pancreas. The
extract has been kept for five days under toluol. When 2 c.c.
of this extract are mixed at room temperature with 1 c.c. of
a two-percent glycogen solution, and to this is added as
quickly as possible a KI-I solution, no change in color is ob-
tained, indicating that the glycogen has been changed into
sugar even in these few seconds. Even when 3 c.c. of the
glycogen solution are added to the extract, the decomposition
of the glycogen occurs so quickly that a reaction with iodine
cannot be obtained. Not until 3 c.c. of the extract are mixed
with 25 c.c. of the glycogen solution (J gram dry glycogen) is
this possible. After this mixture has been kept in the incu-
bator at 37° C. for one-half hour, it, too, no longer gives a
positive iodine reaction. On the following day 0.5 c.c. of the
extract is mixed with 5 c.c. of the glycogen solution. After
standing for eight minutes at room temperature the mixture
has lost its color. The Trommer test is positive. Examina-
tion of the paste from which the extract has been obtained
shows it to be unable to act upon the glycogen.

(/) It seems to be true of a number of the ferments found
in cells and in their secretions that these ferments do not
exist as such in them, but in an inactive form known as
proferments or zymogens. The most striking example of such
a zymogen is probably the entirely inactive proferment of
trypsin (trypsinogen, as it is sometimes called), found in the
pancreatic juice. This proferment (as present in the pan-
creatic juice obtained directly from the pancreatic duct) is
not able to act upon proteins until it has been converted
into trypsin (alkali-proteinase) by coming in contact with a
substance contained in the secretions of the small intestine
(enterokinase). The proferment of alkali-proteinase is found
also in the body of the pancreas, and this fact has been con-

FERMENTS AND FERMENTATION. 93

Bidered in trying to explain why the pancreas is not digested

by its own trypsin, or in general why any organ is not digest ed
by the ferments contained in it. This explanation of the
immunity of tissues against their own ferments can hold in
only a few cases, however. For other enzymes the existence
of proferments has not been so definitely established.

There seems to be little doubt but that proferments exist
for rennin (caseinase), steapsin (lipase), and pepsin (acid-
proteinase). The existence of a proferment ofacid-proteinase
in the gastric mucosa is demonstrated by the following facts:
If the minced mucous membrane of the stomach of an animal
is extracted with a dilute alkaline solution and the whole is fil-
tered, a clear solution is obtained which does notact on proteins.
If this solution is acidulated with hydrochloric acid it digests
proteins rapidly. But if this acid solution is rendered alka-
line once more, and is then again acidulated with hydro-
chloric acid, the digestive properties of the solution for pro-
teins will have been lost. These experimental facts are
explained on the assumption that pepsin is readily destroyed
in an alkaline medium, while its zymogen is not, and that the
conversion of the zymogen into the ferment is accomplished
through the acid.

The relation that ferments bear to their proferments is
not understood. The conversion of the proferment into
the ferment may at times be accomplished through the
action of a specific substance, such as enterokinase. But
the character of this substance, which by some is regarded
as itself a ferment (whence the name), by others as a sub-
stance differing markedly from this group of compounds,
is also not understood. In the majority of instances dilute
acids are able to bring about a conversion of the proferment
into the ferment. Whether this represents more than a
simple change in the physical state of a colloid is still un-
known.

2. Inorganic Ferments. — Beyond what has already been
said we cannot here enter into a discussion of the various

94 PHYSIOLOGY OF ALIMENTATION.

theories of fermentation which have been proposed from
time to time. Within the last few years, however, the work
which has been done on the so-called inorganic ferments
has so altered our older conceptions of the essential nature
of fermentation that a discussion of some of the analogies
between the organic and inorganic ferments may not be
amiss, even though the facts as they stand now have a
greater bearing on the theoretical than on the practical
side of the medical problems of fermentation.

As early as 1863 Schonbein pointed out the analogy which
exists between the influence of finely divided metals (such
as platinum, iridium, silver) and that of a number of ferments
on the velocity of certain chemical reactions. The decom-
position of hydrogen peroxide, for instance, is accelerated
not only by the addition of aqueous extracts of various
animal and vegetable cells which contain ferments, but
also through the addition of the finely divided noble metals
mentioned above. The decomposition of hydrogen peroxide
occurs also in the absence of these substances, only then
much more slowly, so that the finely divided metals possess
the characteristic property of a ferment, namely, that of
altering the velocity of a reaction which occurs in its absence
also.

Through the more recent work of Bredig and with him
von Berneck, Reinders, Ikeda, and the efforts of McIntosh,
Billitzer, Neilson, and others, our knowledge of the inor-
ganic ferments has been greatly increased. For a fuller
account than can be given here and for references to the
literature the reader is referred to the monograph of Bredig.1

In place of the coarsely powdered metals employed by
the older observers, Bredig used so-called colloidal or pseudo-
solutions of these metals. The solutions are prepared by
sending an electric current through electrodes of the noble

1 Bredig: Anorganische Fermente, Leipzig. 1901; Ergebnisse d.
Physiologie, 1902, 1, lte Abth., p. 134.

FERMENTS AND FERMENTATION. 95

metals while these are held in a large dish of absolutely
pure water, The metal emanates in a cloud from one of
the electrodes and remains suspended in the liquid. The
colloidal solution is therefore not a true solution, but rather
a suspension of very fine particles. The coarser particles
are filtered off, and the sol (a term applied to a colloid in
the liquid state) which remains behind shows properties
exceedingly like those of the ordinary ferments. For this
reason these sols have been called inorganic ferments by
Bredig. Depending upon the metal from which the sol
is prepared, we speak of platinumsol, goldsol, etc.

A large number of ferments from different sources have the
power of catalyzing the decomposition of hydrogen peroxide
into water and oxygen. Colloidal solutions of platinum
have the same power. Interestingly enough, as is the case
with the true ferments, this inorganic ferment also is active
in exceedingly small quantities. Thus one gram-atom of
platinum (194.8 grams) diluted with seventy million liters
of water is still able to accelerate the decomposition of
more than a million times its amount of hydrogen peroxide.
One cubic centimeter of the solution which still shows
"fermentative" properties therefore contains only 1/300000
milligram of platinum. It would be difficult to rival this
with figures taken from any of the organic ferments.

The rapidity of the decomposition of hydrogen peroxide
by platinumsol is dependent upon the concentration of the
platinum, just as in the case of a true ferment. If infinite
time is allowed, a small amount of platinumsol will bring about
as much decomposition as a larger amount. In shorter periods
the velocity of the catalysis is definitely dependent upon
the concentration of the colloidal platinum, very much
as in the case of the ordinary ferments which have the
power of catalyzing the decomposition of hydrogen peroxide.

Even though not sensitive to the same degree as organic fer-
ments, the inorganic ferments are exceedingly sensitive to heat.
In the preparation of the sols great care has to be exercised to

96 PHYSIOLOGY OF ALIMENTATION.

prevent overheating of the water, as this causes the platinum,
gold, silver, or whatever metal is being employed, to be
precipitated. In other words, the inorganic ferment is
destroyed. For this reason, therefore, the dish of water
in which the colloidal solution is being prepared is kept
cooled with ice, and overheating by allowing the electric
current to pass through the water for too long a time is
carefully avoided. It was pointed out above that the de-
composition of the true ferments by heat might represent
nothing but a physical change. For, as far as we know now,
the organic ferments are all colloidal solutions, and in con-
sequence exceedingly liable to precipitation (and inactiva-
tion) through heat. The greater sensitiveness to heat in the
case of the true ferments is readily explained on the ground
that these are always impure — mixed with salts, etc., from
which it is impossible to free them — and consequently more
readily precipitated. As will be shown in greater detail
further on, the presence of certain impurities, such as gases
and salts, in the colloidal solutions of platinum greatly
decreases their stability also. Colloidal solutions of platinum,
gold, etc., are the more readily precipitated (destroyed) by
heat the greater the amount of these impurities. It may
be for this reason that the purest ferments which have thus
far been obtained are least sensitive to temperature. Whether
inorganic ferments have an optimal temperature as do the
true ferments is not yet worked out sufficiently. The recent
work of Ernst x shows that such a temperature exists in
the case of the decomposition of oxyhydrogen gas in aqueous
solution in the presence of colloidal platinum.

It was held for a long time that the inorganic ferments
differed from the organic in one essential detail. While the
action of the ordinary ferment comes to a standstill after a
certain time, a reaction catalyzed by an inorganic ferment
seemed always to be complete. It was shown above that

1 Ernst: Zeitschr. f. physik. Chera., 1901, XXXVII, p. 448.

FERMENTS AND FEh'M E.\ TATION. 97

the explanation of this partial decomposition by organic
ferments lay in the fad that their action was reversible,

that they synthesized from the products of the decompo-
sition the substance which was being analyzed. Now it
has been shown by Neilson ' that finely divided platinum
is able not only to hasten the splitting of ethyl butyrate into
ethyl alcohol and butyric acid, but is also able to synthesize
ethyl butyrate from ethyl alcohol and butyric acid. Reversi-
bility is therefore a characteristic of these inorganic ferments
also.2 The failure of the older observers to discover that the
reactions catalyzed by the metallic colloids are incomplete
is to be explained by the character of the reactions which
they studied. In the catalysis of hydrogen peroxide, for
example, by platinumsol, one of the products of the decom-
position— the oxygen — is allowed to escape as soon as liberated,
so that even if water could be oxidized to hydrogen peroxide
it would not occur under the conditions of the experiment.
For, in order that reversion may occur, all the products
of the decomposition must be allowed to accumulate. If
the products of a chemical reaction catalyzed by any fer-
ment are removed as fast as formed, that reaction is com-
plete and shows no "limit."

A great analogy exists also between the sensitiveness of
the true ferments to certain poisons and the sensitiveness
of the colloidal solutions of the noble metals to these same
poisons. Acids, bases, and salts affect different organic
ferments in different ways. The effect of these same sub-
stances upon the inorganic ferments is equally marked.
The addition of a mere trace of disodium phosphate to a
liter of colloidal platinum solution caused an immediate
fall in the "velocity constant" of the decomposition of
hydrogen peroxide from 0.023 to 0.015. After waiting several

'Neilson: Science, 1902, XV, p. 715.

2 The spongy platinum used by Neilson is no! a colloid, bul the nature
of its action is no doubt the same as that of platinumsol.

98 PHYSIOLOGY OF ALIMENTATION.

days the velocity constant had fallen lower still — to 0.01 1.
We are familiar with this same inactivation in the case of
the true ferments, and it is not impossible that that which
causes the platinumsol to become inactive, namely, a pre-
cipitation of the colloidal par icles, lies at the basis of the
inactivation of the true ferments also.

Poisons, the action of which upon organic ferments is more
or less characteristic and striking, show this same action
when brought in contact with inorganic ferments. The
physiological action of hydrocyanic acid finds its explana-
tion in its power to interfere with the oxidizing ferments
of the cell. When added in even exceedingly minute traces
to oxidizing (and other) ferments it reduces their action to a
point where it can scarcely be recognized. The addition of
hydrocyanic acid to platinumsol reduces its action upon hydro-
gen peroxide in the same striking way, for the presence of
0.0014 milligram hydrocyanic acid in a liter of the colloidal
platinum solution reduces its action one-half. Hydrogen
sulphide, which also has a powerful action in inhibiting the
activity of organic ferments, shows the same behavior when
added to the colloidal solutions of the noble metals. The order
in which the poisons, ferments, and hydrogen peroxide are
put together is not without influence upon the extent of the
inhibition produced. The fact is therefore of interest that
the order which is most effective in reducing the action of
an organic ferment is also the most effective when an in-
organic ferment is dealt with.

CHAPTER V.

THE ACTION OF THE ENZYMES FOUND IN THE HUMAN
ALIMENTARY TRACT.

i. Amylase (ptyalin, amylopsin, diastase) is the term
applied to the enzyme found in the salivary and pancreatic
secretions, which has the power of acting upon starch and
producing from it maltose and dextrin. The ferment is
found in other tissues of the body also, as well as in germinat-
ing cereals of all kinds (rice, corn, oats, etc.). The alimentary
secretions of all animals do not contain amylase. The saliva
of the dog, for instance, contains no starch-splitting ferment,
and the same seems to be true of all carnivora. The amylase
of the parotid seems to be present in the human being im-
mediately after birth, but the starch-splitting ferment of the
pancreas does not appear until a month or more later.

We recognize the presence of amylase by its power of acting
upon starch and its ready destruction by heat rather than by
any analytical means at our disposal. As with practically all
enzymes, amylase has not yet been obtained in a pure state.
Cohnheim 1 has succeeded in obtaining the amylase of the
saliva as a gray powder of fairly constant composition by
acidifying the collected saliva with phosphoric acid and
neutralizing subsequently with dilute calcium hydroxide.
The amylase is carried down mechanically with the precipi-
tate of calcium phosphate, and after filtering is redissolved by
the addition of water. From this aqueous solution the amylase
can be ropreci pita ted by alcohol in order to further purify it.

' Cohnheim: Virchow's Archiv, 1863, XXVIII, p. 241.

99

100 PHYSIOLOGY OF ALIMENTATION.

The amylase of the pancreas is obtained in a very active
state by Robert's method of precipitation with alcohol and
re-solution in water. The method of Cohnheim for obtaining
the starch-splitting ferment of the saliva has also been applied
to the pancreas, though Robert's method seems to give a
more active preparation.

The most frequently utilized source of amylase to-day is
probably germinating malt, which contains this enzyme in
enormous quantities. Effront's a method of obtaining the
ferment from this source consists in the extraction of finely
ground malt with water for some time, filtration, and alco-
holic fermentation of the nitrate through the addition of
yeast. After a second filtration the amylase is precipitated
from the filtrate through the addition of alcohol. Effront
obtained in this way from every 100 grams of malt 3 to 3J
grams of a white substance which, when redissolved in water,
was as active as 80 grams of the original malt.

Much discussion has arisen as to the identity or non-identity
of the amylase obtained from various sources. So far as the
qualitative character of the action of the amylase on starch is
concerned, there seems to be no difference, whatever be the
origin of the ferment. Quantitatively the pancreatic amylase
acts more powerfully than the salivary, but this is explicable
on the basis of mere differences in the concentration of the
enzyme in the two secretions.

Other characteristics, such as differences in sensitiveness
to heat, alkalies, acids, salts, etc., have also been brought
forward in support of the independent nature of the starch-
splitting ferments from different sources, but great care must
be exercised in accepting these arguments. As already stated,
amylase has not yet been obtained in a pure state. The
impurities which accompany any preparation of amylase are
different, depending upon the source of the ferment. Even

1 Effkont: Die Diastasen. Translated into German by Bucheler,
Leipzig u. Wien. 1900, 1, p. 113.

ACTION OF THE ENZYMES 101

the same source docs not always yield the same impurities.
It is therefore entirely probable that the differences which
have been assumed to exist in the amylase obtained from dif-
ferent sources are only apparent, and depend upon the fad
that the impurities accompanying the ferment are different.
In this way the same ferment is simply compelled to work
under different external conditions, and, as will be shown
immediately, the medium in which amylase acts has an im-
portant influence upon its action. What has been said here
of amylase holds also for the other ferments.

Amylase brings about two changes when allowed to act
upon starch — it liquefies the starch and converts it into sugar.
The sugar which is formed by amylase when unmixed with
other enzymes is the disaccharide, maltose. When amylase is
allowed to act upon raw starch granules, the latter are seen
to be gradually eroded, and sugar is formed. Upon boiled
starch amylase acts far more energetically, the conversion
into sugar being accomplished in much shorter time. Accord-
ing to Kuhne, the amylase of the .saliva does not act upon un-
boiled starches at all, while that of the pancreas does. It is
entirely probable, however, that this difference is only appar-
ent and dependent upon the fact that the concentration of
the amylase in the saliva is less than that in the pancreatic
juice. The chemical change which starch suffers under the
influence of amylase is indicated in the following formula:

CioH2o01o H-HoC^C^H-a^Oii-

Starch Water Maltose

This formula shows that starch undergoes a hydration
when acted upon by amylase, but it tells us nothing of the
mechanism of this change. That maltose is the ultimate
product of the catalytic change is almost universally accepted
but opinions differ widely as to the intermediate changes
which occur in the starch before the final stage of maltose is
reached. All observers are agreed, however, that dextrin is
formed in the process of saccharification. Whether the dex-

102 PHYSIOLOGY OF ALIMENTATION.

trin is formed from the starch and is subsequently changed
into sugar, or whether dextrin and sugar are formed simul-
taneously, is not yet settled. If the former is ths correct
view, it would be expressed by the formula

Ci2H2o010 =C12H2oOio. (1)

Starch Dextrin

Ci2H2o01q4-H20 = Ci2H22011. (2)

Dextrin Water Maltose

If the second theory, that of Museums, is the correct one,
the following equation would hold:

2 Ci2ff2oO!o+H20= Ci2H2201i +Ci2H2oOio.

Starch Water Maltose Dextrin

The majority of authors also believe that the dextrin formed
is not all of the same kind, that, in other words, several dex-
trins are formed, which have been distinguished by different
names. The basis for this belief lies in the fact that the
dextrins obtained at different stages in the saccharification
of starch are not converted into maltose with the same rapidity
when acted upon by amylase under normal circumstances
or in the presence of acids, salts, various organic substances,
etc. It seems probable, however, that these differences rest
more upon physical than upon chemical characteristics of
the dextrin. Dextrin belongs to the group of substances
known as colloids,1 and the properties which have been
considered characteristic of different dextrins might readily
characterize one and the same chemical substance in differ-
ent physical states. A dextrin solution in which the particles
are finely divided would, for example, be more rapidly con-
verted into sugar than one in which the suspended particles
are coarser.

Amylase may be used as a type to illustrate some of the
characteristics of a ferment. Amylase accelerates a chemical

1 See Chapter XIV, Part 2.

ACTION OF THE ENZYMES. 103

reaction which occurs also in its absence, only then exceed-
ingly slowly. Starch paste by itsolf kepi a! a suitable tem-
perature is very slowly converted into maltose. Amylase
is therefore a positive catalyzer. The influence of tem-
perature upon the activity of this ferment has been
worked out by Kjeldahl. At 0° C. amylase acts exceedingly
slowly, but its activity increases rapidly with an increase
in temperature until 35° C. is reached. From 35° to a
little above 60° C. a further but less marked increase is
observed. Beyond this point the activity of the ferment
falls off rapidly until at 70° C. it acts no more energetically
than at about 15°. A curve similar to those shown on p. 89
would therefore represent graphically the influence of tem-
perature upon amylase.1

The reaction which amylase catalyzes is incomplete when
allowed to take place in glass, the saccharification coming to
a standstill when less than half of the total starch present has
been converted into maltose. The exact point varies with ex-
ternal conditions of temperature, concentration, etc. We shall
see later that this fact indicates that the action of amylase is
reversible. Evidence of the truth of this statement has recently
been brought by Criomer,2 who has shown that a ferment
(perhaps identical with amylase) which has the power of
splitting glycogen (an isomer of starch, and often called
animal starch) into glucose is also able to synthesize glycogen
from glucose.

If sufficient time is given, the amount of change brought
about in a starch paste is the same, no matter what the
concentration of the amylase.

The activity of amylase is markedly influenced by the
presence of different chemical substances in the reaction
mixture. Amylase seems to act best in a neutral medium.

1 See Effront: Die Diastasen. Translated into German by Buche-
lbr, Leipzig, 1900, I, p. 119.

2 Cremer: Ergebnissed. Physiol., 1902, L, He Abth. p N0.'>.

104 PHYSIOLOGY OF ALIMENTATION.

Both acids and alkalies soon bring its activity to a stand-
still, even in very moderate concentrations. The influence
of acids upon amylolytic activity is of physiological impor-
tance, because the chewed food mixed with saliva passes
into the stomach. The concentration of the acid in the
stomach is sufficient to stop the activity of the amylase;
but, as will be remembered from what has been said before,
the amylase continues its action for some time, especially
in the cardiac end of the stomach, as the food which passes
into this viscus is not at once rendered acid by its secre-
tions.

It has been shown by the work of Cannon that the saliva
does not act best in the concentration in which it is poured
out upon the food, but when diluted with about three times
its bulk of water. The explanation of this fact lies no
doubt in the dilution of the products of amylolytic activity,
for in a concentrated solution the point at which the reac-
tion comes to a standstill is reached sooner than in a more
dilute one. In fact, most fermentation mixtures which
have come to a standstill will go on further if only water
is added. The use of water with meals, after thorough
mastication of the food, is therefore not only not harmful,
but useful. Dilution of the stomach contents hastens the
activities of the enzymes here also. The presence of water
in the stomach, moreover, increases the secretion of gastric
juice and hastens absorption. The evil consequences of the
consumption of water with meals lie in its use before masti-
cation of the food, thus preventing thorough insalivation and
the good effects of this process upon the food; and in the use
of too cold water, whereby the reaction velocity of all fer-
mentative changes is markedly decreased.

2. Maltase (glucase) is an enzyme the characteristic activ-
ity of which lies in its power of splitting maltose into two
molecules of dextrose. It is able to act also upon starches
and dextrins, but only exceedingly weakly when compared
with amylase, the ultimate product from these substances

ACTION OF THE ENZYMES. 105

also being dextrose. Maltose is formed as an intermediate
product, so that what was defined as the characteristic ac-
tivity of maltase appears here also. It is evident from this
that care must be exercised in deciding whether a ferment
present in animal or vegetable tissues and capable of pro-
ducing a sugar from starch is amylase or maltase, or whether
both are present. The recognition of the first is dependent
upon the identification of maltose as the end-product of the
reaction, that of the latter upon the recognition of dextrose.
The existence of maltase in the presence of amylase can be
proved by isolating a ferment which splits pure maltose into
dextrose. The recognition of amylase in the presence of
maltase is more difficult, and differences in resistance to
heat, chemical reagents, etc., must be utilized to bring about
their separation.

Maltase seems to have been first discovered by Bechamp
in the urine, and somewhat later by Brown and Heron in the
pancreatic juice and in the small intestine. It is found also in
the saliva. The commonest source of maltase to-day for the
study of its activities is corn, from which it can be obtained
in a very active state, by precipitation of a dilute acid-
alcohol extract of this cereal with strong alcohol.1 The
ferment when obtained in this way is not pure.

Qualitatively the maltase obtained from different sources
shows the same action upon maltose. Considerable differ-
ences exist, however, in the resistance of this enzyme to
external conditions when obtained from different animal
tissues or cereals. This has been taken to argue in favor
of the existence of different maltases. Since maltase has
not yet been obtained in a pure state, however, we can-
not be sure whether the differences found in the various
maltase preparations are due to specific differences in the
ferments themselves or to differences in the impurities with
which the preparations are contaminated.

1 Beueiunck: Centralbl f. Bakteriologie, 1898, xxiii, 2te Abth.

106 PHYSIOLOGY OF ALIMENTATION.

Lintner and Kroeber * give as the optimal temperature for
the action of yeast maltase upon maltose 40° C. Below and
above this point the formation of dextrose proceeds much
more slowly. At 50° C. this maltase is almost entirely
destroyed. Cusenier gives 56° to 60° C. as the optimal
temperature for the maltase obtained from corn.2

Maltase is of special biological interest, as it was in a
study of this ferment that the fundamental fact of the
reversible action of enzymes was first experimentally proved by
the interesting work of A. Croft Hill.3 For a better under-
standing of this property of enzymes a few introductory
words are necessary to illustrate the general conceptions of
chemical equilibrium and reversion.

If a number of substances capable of reacting chemically
with each other are brought together, a reaction ensues,
which after a time comes to a standstill (practically speak-
ing). We. say then that the system is in chemical equilib-
rium. If, for example, at a definite temperature chemically
equivalent amounts of acetic acid and ethyl alcohol are
mixed together, a reaction ensues according to the following
equation:

CH^COOH +C2H5OH =CH3COOC2H5 + H20.

Acetic acid Ethyl Ethyl acetate Water

alcohol

The reaction takes place in the direction from left to right.
If chemically equivalent amounts of ethyl acetate and water
are mixed together, ethyl alcohol and acetic acid are formed.
In other words, the above reaction takes place from right
to left. Neither in the first nor second instance does the
reaction become complete. Before the given amounts of

1 Lintner and Kroeber: Berichte d. deutschen chem. Gesellsch.,
1895, p. 1050.

2 Quoted from Effront: Die Diastasen. Translated into German
by Bucheler, Leipzig u. Wien, 1900, I, p. 225.

3 Hill: Jour, of the Chem. Society, 1898, LXXLTI, p. 634; Berichte
d. deutschen chem. Gesellsch., 1901. XXIV. p. 1380.

ACTION OF THE ENZYMES. 107

acetic acid and ethyl alcohol, or ethyl acetate and water,
have undergone complete decomposition the reaction comes

to a standstill.

A reaction such as wc have just spoken of, which can lake
place from right to left as well as from lefl to right, is called
a reversible reaction. We indicate such a reversible reaction
as follows:

CH3COOH +C2H5OH <=> CH,COOC2H5 +H20.

Acetic acid Ethyl Ethyl acetate Water

alcohol

It can readily be seen that when equilibrium is estab-
lished in a reversible reaction the four substances reacting
with each other are present in the reaction mixture. The
characteristic feature of such a condition of equilibrium is
found in the fact that under the same external conditions
it is always the same no matter from which side it is reached.
In other words, it is immaterial whether chemically equivalent
amounts of acetic acid and ethyl alcohol or chemically
equivalent amounts of ethyl acetate and water are mixed
together. The condition of equilibrium reached in either
case is the same.1

Although we say ordinarily that when chemical equilibrium
has been established the reaction has come to a standstill,
this is in reality incorrect. When chemical equilibrium is
established between the two members of a chemical equation
it really means that the chemical changes are still going on,
only the amount of change in the one direction is exactly
counterbalanced by the reverse change in the opposite
direction. The reaction is therefore stationary.

As has long been known, maltase acting upon maltose is
unable to bring about its complete analysis into dextrose.
The reaction comes to a stands! ill when some 85 percent of
the original maltose is split. Hill now tried the interesting

1 Pen Cohen Physical Chemistry lor Physicians. Translated by
Martin M. Fischer, New York, 1903, p. 68.

108

PHYSIOLOGY OF ALIMENTATION.

\

experiment of allowing yeast maltase to act at 30° C. upon a
40-percent solution of dextrose for a number of months, and
found that this same ferment, which is able to bring about the
analysis of the maltose, is also able to bring about its syn-
thesis from the products of the analysis. Hill determined
the appearance of maltose and its gradual increase in the dex-
trose solution by means of the polariscope and copper reduc-
tion tests. Since maltose is able to rotate the plane of polar-
ized light more to the right than dextrose, and since dextrose
has a greater reducing power than maltose, it is possible
through analysis to determine whether in a mixture of the
two sugars one is increasing at the expense of the other.
Column A in the following table shows how, under the influ-
ence of yeast maltase, the rotating power of a pure dextrose
solution gradually increases, while column B shows how its
reducing power gradually decreases. Columns C and D indi-
cate the percent of maltose contained in the originally pure
dextrose solution, as calculated from the figures obtained in
the first two columns. The values obtained by the two
methods of analysis agree very well.

Duration
of experiment

0 days
5 "
14 "
28 "
42 "
70 "

A.

Rotation.

52.5°
55.0°
58.3°
60.3°
62.7°
63.6°

B.

Reduction.

100.5
97.7
95.8
94.0
92.5
90.6

C.

Maltose in %.

0.0
3.0

7.4
10.0
13.0
14.0

D.

Maltose in %.

0.0

3.5

6.8

10.0

12.0

15.0

Maltase seems, therefore, to have a reversible action and
is able not only to split maltose into dextrose, hut, also to svn-
fflgp the rHgflPfVifirirle from the monosaccharide. The
I chemical reaction expressing this may be written as follows:

C12H220ii +H20 +± C6Hi203+C6H1206.

Maltose Water Dextrose Dextrose

ACTION OF THE ENZYMES. 109

This equation is entirely analogous to (lie one given on page
107. As in the case of ethyl acetate and water, we have here
also a reaction which can take place in either direction. No
matter from which side we begin, the final result is always I he
same — the presence in the reaction mixture of maltose an
water side by side with two molecules of dextrose. The onl
difference between the reaction discussed on page L07 c\n<\ this
one is that the analysis or synthesis of maltose occurs under
the influence of a catalyzer. But, as has been pointed out, a
catalyzer only alters the rate of a chemical reaction and does
not enter into the reaction itself (unless it does so tempora-
rily). The analysis or synthesis of maltose would occur in the
same way, and the state of equilibrium finally attained be the
same, even if no maltase were present, only under such cir-
cumstances the velocity of the reaction would be very low.
The system

Maltose + Water <=± Dextrose -f Dextrose

is in equilibrium under the conditions existing in Hill's experi-
ments when some 85 percent of dextrose exists beside about 15
percent of maltose. It is clear that such a mixture of the two
sugars in water will undergo no apparent change whether mal-
tase be present or not. As shown above, however, the reaction
has not ceased, only the chemical change in the one direction
just counterbalances that in the opposite, so that outwardly
everything remains the same. But what must occur if into
the above reaction mixture some maltose or some dextrose is
introduced, or either of these substances is removed? It is
clear that this must disturb the chemical equilibrium existing
between the maltose on the one hand and thedextrose on the
other. Whenever this occurs the activity of maltase as an
agent hastening the establishment of a state of equilibrium
between these two substances must come into play, and must
either analyze or synthesize maltose until such a state of
equilibrium is again established. The introductioo of dex-

110 PHYSIOLOGY OF ALIMENTATION.

trose or the removal of maltose from a reaction mixture con-
taining the two sugars in chemical equilibrium would there-
fore be followed by a synthesis of maltose, while the introduc-
tion of maltose or the removal of dextrose would be followed
by an analysis of the disaccharide if other external conditions
remained the same.

3. Caseinase (rennin, rennet) is the name given to a ferment
found in many animal and vegetable cells and their secretions,
which has the power of changing caseinogen into casein —
that is, the power of curdling milk. In the human being the
ferment is found in the secretions of the stomach from birth.
Milk-curdling ferment is found also in the pancreatic juice,
and though it differs somewhat from the caseinase found in
the stomach in its resistance to heat and chemical agents, it
is probably the same substance and may well be called by the
same name.

A number of authors have pointed out the fact that case-
inase always coexists with a proteolytic ferment. In the case
of the human being (and certain other animals) caseinase
accompanies the acid-proteinase (pepsin) of the stomach and
the alkali-proteinase (trypsin) of the pancreas. Caseinase,
moreover, is found in largest amount in those portions of the
stomach where the most acid-proteinase is found, namely, the
fundus. The constant association of the two enzymes has
given rise to the idea that they probably represent a giant
molecule, the different portions of which have different fer-
mentative functions and are differently affected by external
conditions. It has been shown by Herzog, for example, that
antiproteinase (antipepsin) added to the combined ferments
inhibits only the proteolytic action, while the milk-curdling
action goes on undisturbedly. Digestion with weak acids will
at proper temperature quickly destroy the caseinase con-
stituent of the entire molecule, and by mechanical precipita-
tion Hammarsten has succeeded in obtaining a caseinase solu-
tion free from any proteolytic activity.

Preparations of caseinase are obtained by extracting, with

ACTION OF THE ENZYMES. Ill

solvents of various kinds, the stomach of (lie calf, which con-
tains the enzyme in enormous quantities. Among these
sodium chloride and hydrochloric acid solutions may be men-
tioned. Glycerine is also used extensively. When purer
preparations are required, precipitation with alcohol, filtra-
tion, and re-solution in water are necessary.

Caseinase behaves like other ferments in that it is readily
destroyed at a rather low temperature. A few minutes',
exposure in a neutral solution at 70° C, or in an acid solu-
tion at 63° C, suffices to do away with all milk-curdling
properties. In an alkaline medium the ferment is affected
rapidly even at a very low (room) temperature. Though
active in a faintly acid or alkaline medium, caseinase acts
best in a neutral medium and at a temperature of about
40°. Below and above this point the rapidity with which
milk is made to coagulate falls off rapidly.

The mechanism of the coagulation of milk has been studied
by a number of authors. Briefly summarized it may be
stated as follows: Milk contains a protein substance to
which the name caseinogen has been given (casein of Ham-
marsten), the change of which into casein (paracasein of
Hammarsten) is the essential change in the curdling of
milk. Casein is formed from caseinogen under a number
of circumstances. This occurs when acid is added to the
milk, or when any acid-producing change occurs in the
milk such as "souring " under the influence of bacteria,
or when an electric current is passed through the milk.
But milk is caused to coagulate most rapidly in ordinary
alimentation through the addition of caseinase. In the gastro-
intestinal tract two agencies are active in bringing about the
coagulation of ingested milk: first, the hydrochloric acid of
the gastric juice, and secondly, the presence of caseinase in
the gastric and pancreatic secretions. Another source of
caseinase in the alimentary trad is found at times in cer-
tain bacteria which may be present.

When caseinase is added to milk the latter soon sets into

112 PHYSIOLOGY OF ALIMENTATION.

a solid mass which contracts after a time and squeezes out
a yellowish fluid — the whey. The clot consists of casein
in the meshes of which there is found the fat of the milk.
The whey contains lactalbumin and lactglobulin, two pro-
tein bodies which have nothing to do with the curdling of
the milk, together with the sugar of the milk and most
of its salts.

In the coagulation of milk during ordinary digestion three
substances are involved — caseinogen, caseinase, and certain
salts. It was first shown by Hammarsten that calcium
salts play an important role in the curdling of milk. As
will be shown immediately, however, calcium 'represents
only one of a large number of salts which can influence
the coagulation of milk. Various theories have been pro-
posed from time to time to explain fehe interaction of the
three substances. These have in the main been of a chem-
ical nature, and have assumed the production of true chem-
ical combinations between caseinogen and calcium, etc.
The recent work of Conradi and of Loevenhart speak
against this idea and indicate that in the curdling of milk we
are dealing with a physical process in which the colloid casein-
ogen which exists in ordinary milk in a liquid or sol state is
converted into the solid or gel state which we term casein.
Caseinogen and casein (casein and paracasein of Hammar-
sten) are therefore the same chemically, but. different physi-
cally in that the former consists of small particles suspended
in the liquid portion of the milk, while the latter represents
these same particles clumped. The passage from the sol to
the gel state is influenced by the ferment caseinase and cer-
tain salts.

Casein can be precipitated by all methods used for this
purpose much more easily than can caseinogen. But if
the proper concentration is employed the latter is brought
down also. It is concluded from this that casein exists in
a coarser state of aggregation than caseinogen. Nor can
the differences which have been said to exist between case-

ACTION OF THE ENZYMES. 113

inogen and casein be taken to indicate that they are nol the
same chemically, for all the stated differences can easily be

explained on the assumption that the two represent physical
modifications of one and the same substance.

As stated above, calcium sails are not the only ones
to bring about a precipitation of casein. At the proper
concentration a large number of salts cause the precipitation
not only of casein but of caseinogen as well. Arranged in
the order of their effectiveness the salts of the different
metals read as follows:

(1) Metals which precipitate neither casein nor caseinogen:
Sodium, potassium, ammonium, rubidium (?), caesium (?).

(2) Metals which at room temperature quickly precipi-
tate casein, but caseinogen only after remaining at 40° C.
for some time or on heating to a still higher temperature:
Lithium, beryllium, magnesium, calcium, strontium, barium,
manganese (ous), iron (ous), cobalt (ous), nickel (ous).

(3) Metals which precipitate both casein and caseinogen
at room temperature: The remaining heavy metals, includ-
ing iron (ic).

As we pass from the first group through the second to
the third, the precipitating power of the metals for both
casein and caseinogen increases progressively.1

1 See Osborne: Journal of Physiology, 1901, XXVII, p. 398; Con-
radi: Mi'inchener medizinalische Wochenschr. XL VIII, 1901, (l),p. 17");
Loevenhart: Zeitschrift fur physiologist-he Cheinie, 1904, XLI, p. 177.

CHAPTER VI.

THE ACTION OF THE ENZYMES FOUND IN THE HUMAN
ALIMENTARY TRACT (Continued).

4. Acid-proteinase (pepsin). — By this term is understood
a proteolytic ferment which acts only in the presence of
an acid. Acid-proteinase is found widely distributed in
nature in both animal and vegetable cells. It is found in
many regions in the human body, more especially in the
muscles, and, what interests us most in this connection, in
the mucous lining and secretion of the stomach. Acid-
proteinase has the power of acting upon proteins in the
presence of certain acids and splitting these proteins into
a series of simpler substances. What these simpler sub-
stances are will be discussed further on.

Acid-proteinase is present in the stomach of the human
being from the time of birth. Neither at this time nor later
in life, however, do all parts of the stomach contain it in
the same amount. The cardiac end of the human stomach
contains much more than the pyloric end.

Pure preparations of acid-proteinase are exceedingly dim-
cult to obtain. Extraction of the mucosa of the pig's stomach
with a 0.2 percent hydrochloric acid solution or with glycerine
yields very active preparations. These are, however, very
lmpure. Brucke's method of extraction of the mucous
membrane with dilute phosphoric acid and subsequent
neutralization with calcium hydroxide seems to yield very
pure acid-proteinase. The enzyme is carried down mechan-
ically with the precipitate of calcium phosphate, and can be

114

ACTIOS OF THE ENZYMES. 115

subsequently rcdissolved in water. PEKELHARING ' claims to
have prepared the purest acid-proteinase thus far obtained
and classes the enzyme union- the proteins. His prepara-
tion gives the well-known reactions for proteins, and on
quantitative analysis shows the presence of carbon, nitrogen,
hydrogen, and sulphur in the proportions in which they
exist in these bodies. As the preparation contains no phos-
phorus it is not considered a nucleo-proteid. In harmony
with the findings of Nencki and Sieber, Pekelharing looks
upon chlorine as a constant constituent of acid-proteinase.
Should it be shown ultimately that Pekelharing's enzyme is
not a pure substance it will still have to be looked upon as
the most active preparation of this ferment obtained thus far.
0.001 milligram in 6 c.c. of a 0.2 percent hydrochloric acid
solution dissolved a flake of fibrin in a few hours.

The acid-proteinase of Pekelharing is able not only to act
on proteins but also curdles milk. This means that acid-
proteinase and caseinase are probably parts of the same
molecule. As stated above, gastric juice contains a fat-split-
ting ferment — lipase — but the pepsin preparation of Pekel-
haring shows no fat-splitting activity. This author's work,
therefore, supports a view which has been suggested by
Nencki and Sieber before him, that acid-proteinase and
caseinase represent different parts of a giant molecule.

Brunton,2 and Friedenthal and Miyamota3 have ex-
pressed themselves as opposed to the conception of the protein
character of pure acid-proteinase and bring forward as proof
that they have succeeded in obtaining active acid-proteinase
preparations which do not give any of the reactions for pro-
teins. It is also pointed out by these authors that acid-pro-
teinase is not digested by alkali-pro teinase (trypsin), which as

1 Pekelharing: Zeitschrift fur physiologische Chemie, 1902 XXXV
p. 8.

2 Brunton. Centralblatt fur Physiologie, 1902. XVI, p. 201.

3 Friedenthal and Miyamota: Centralblatt fur Physiologie 1901,
XV, p. 7s<i; ibid., 1902, XVI, p. 1,

116

PHYSIOLOGY OF ALIMENTATION.

is well known acts upon all proteins thus far studied. Against
Friedenthal and Miyamota can be brought the argument
that their preparations were not very active and so may
have contained too little of the pure enzyme to give the
protein reactions. Further study of the subject is, however,
necessary before the question can be looked upon as settled.
Acid-proteinase acts only in an acid medium, but the kind
of acid is not immaterial. Hydrochloric acid furnishes by
far the most favorable medium, but nitric, sulphuric, phos-
phoric, lactic, acetic, tartaric, etc., are also active. Pflei-
derer,1 who has investigated the question physico-chemically,
comes to the conclusion that, broadly speaking, different
acids favor the action of acid-proteinase on fibrin, according
to their "avidity," those with the greater "avidity" acting
more powerfully than those with a lesser one. Since we now
know that the "avidity" or "strength" of an acid is an
expression of the number of free hydrogen ions it yields
upon solution, the above statement may be said to mean
that those acids which yield the largest number of hydrogen
ions when dissolved in water are most powerful in furthering
the activity of acid-proteinase. The following table may
serve to illustrate what has been said as well as serve as a
text for that which is to follow. The degree of fibrin diges-
tion as measured by Grutzner's method2 is expressed in

Degree of color after

Name of acid,
all 3^ normal.

5
min.

10
min.

20

min.

30
min.

1
hr.

1*

hrs.

2

hrs.

5

hrs.

10

hrs.

24
hrs.

Nitric

1
0
0
0
0
0

5
0-1
0
0
0
0

5-6

1
0-1

0

0

0

6
2
1
0
0
0

6
3-4
3-4
0-1

0

0

6
5
5-6
1
0
0

6
5
6
2-3
0
0

6
5-6
6
4
0
0

6
6
6
5-6
0
0

6
6

Lactic

6

6

0

0

1 Pfleiderer: Pfluger's Arch., 1897, LXVI, p. 605.

2 See p. 130.

ACTION OF THE ENZYMES. 117

figures from 1 to 6, according to the amount of color pro-
duced. In each digestion -tube were present the same amounts
of fibrin and pepsin and chemically equivalent amounts
of the various acids.

At a somewhat higher concentration (for example, 1/20
normal) both the acetic and sulphuric, acid tubes would
have shown some degree of fibrin digestion, but the order
of the table would not have been much different. With-
out further comment, therefore, it is clear that while the
effect of any acid upon the proteolytic activity of acid-
proteinase is chiefly a function of the number of hydrogen
ions which the acid yields on solution in water, the indi-
vidual acids vary enough from each other even when the
number of hydrogen ions in the unit volume of the digestion
mixture is the same to make us inquire after the cause of
this difference. Sulphuric acid, for example, which in
dilute solution is dissociated to about the same degree as
hydrochloric, stands far below this in its power of bringing
about a demolition of the protein molecule. Now since
sulphates in general (sodium sulphate, magnesium sul-
phate, etc.) markedly retard the activity of acid-protcinase
even when this is acting in the presence of hydrochloric
acid, it lies near at hand to consider the S04 constituent
of the sulphuric acid and of these salts as chiefly respon-
sible. Other salts, such as the chlorides and iodides of
sodium, potassium, and ammonium, also inhibit the diges-
tion of a protein under the influence of acid proteinase and
hydrochloric acid, but not so markedly as the sulphates.

The reason for the individual differences between the
acids and the effect of various salts upon the velocity of
digestion is not yet entirely clear. It is evident that the
nature of their action might be various. In looking over
Pfleiderbr's tables, however, one is struck with the parallel-
ism which exists everywhere between the effect of the different
acids and the various salts upon the rate of digestion and
the degree of swelling which these substances bring about

118 PHYSIOLOGY OF ALIMENTATION.

in fibrin alone. As is well known, fibrin swells in different
acids, but not to the same degree in each. If now the
acids are arranged according to the degree in which they
make fibrin take up water (swell), this order is the same
as that given above for the effect of these same acids on
digestion under the influence of acid-pro teinase. Sulphuric
acid, for example, which stands very low in the list of acids
as favoring acid-pro teinase digestion, occupies a similar
position when the acids are arranged in the order in which
they cause fibrin to swell. What has been said of the acids
holds also for the salts. The more a salt inhibits the absorp-
tion of water by fibrin (for example, a sulphate) the more
does this salt retard the digestion of a protein.

The effect of various external conditions upon the proteo-
lytic activity of acid-proteinase has usually been attributed
to the effect of these conditions upon the acid-proteinase
itself. Unquestionably external conditions can most markedly
influence the state of the ferment itself — it is no doubt a
colloid and influenced, as are all colloids, by external con-
ditions— but in the experiments which have been cited, the
chief effect of the external conditions seems to have been
on the protein undergoing digestion. Bruckb many years
ago pointed out that the more fibrin has swelled the more
rapidly it is digested. The different acids and salts in-
fluence this swelling in different degrees, in consequence of
which the protein is attacked by the acid-proteinase with
greater or less ease. It seems to me that this difference
between the physical change which a protein suffers when
it swells during the process of peptic digestion, and the
chemical change which probably constitutes the real activity
of the proteolytic ferment when the simpler digestion-
products are formed, has never been sufficiently well drawn.
The two are different, and differently influenced by external
conditions.

The optimum concentration of hydrochloric acid for the
activity of acid-proteinase varies with the protein which

A CTION OF Til E i:.\ ZYM ES. 119

is being acted upon. Hammarsten gives 0.08 to 0.1 per-
cenl for fibrin; 0.1 percenl for myosin, casein, and vegetable

proteins; 0.25 percent for coagulated white of egg.

Alkalies and alkaline salts when present in a digestion
mixture are uniformly injurious in I heir action. If pro-
teins are present at the same time with the acid-proteinase,
alkalies act less destructively, no doubt because the alka-
lies combine with the protein. This is indicated by the
Eacl that the same concentration of alkali acts the less
deleteriously upon the acid-proteinase the greater the amount
of protein present.1 Of other substances which, when
present, influence the activity of acid-proteinase and which
are of medical interest, the following may be mentioned:
Alcohol and tannic acid interfere with the action of the
ferment, as do most alkaloids and carbohydrates. Bile
also belongs in this group, for one part of this substance is
able to do away entirely with the proteolytic activity of
five hundred parts of gastric juice. Caffein and theobromin
further the action of the enzyme.2

Within certain limits the rapidity with which acid-pro-
teinase splits a protein increases with an increase in the
quantity of the ferment present in the reaction mixture.
But in no case is the digestion of the protein complete unless
the products of the reaction are removed. An accumulation
of the products of digestion retards markedly the further
analysis of the protein. It will be shown further on that
this is probably dependent upon the fact that the action of
acid-proteinase is reversible, and that the ferment synl he-
sizes from the products of the digestion the protein itself,

' See Langley. Journal of Physiology, 18S2, 111, pp. L'53 mid 283;
Langley and Edkins: ibid., 1886, VII, p. 371.

Wroblewski. Zeitschrift fur physiologischc Cliemie, 1S95, XXI,
p. 1; also Buchner. Berichte der deutschen chem. Gesellschaft, 1897,
XXX1I1, p. 1110; Laborde: Comptes rendus Soc. biol., 1S09, LI, p.
821; Xirenstein and Schipf. Archiv KirVerdauungskrankheiten, 1902,
VIII,p.559. Bruno. Pawlow's Workoi the Digestive Glands. Trans-
lated by Thompson London, 1902, p. 15S.

120 PHYSIOLOGY OF ALIMENTATION.

in a way analogous to that described for the action of mal-
tase on maltose.

Acid-proteinase is, like other ferments, very sensitive to
temperature. At 0° C. it is scarcely active. From this point
to 35° C. the velocity of its action increases progressively,
attaining an optimum between 35° and 50° C. Beyond this
point its activity diminishes.1 In a neutral solution the fer-
ment is in a, few minutes destroyed at 55° C. The presence
of hydrochloric acid protects the ferment against destruction
by heat, so that when present in the concentration in which
the acid is found in the stomach, the ferment is destroyed only
slowly until 65° C. is reached. Peptones and certain salts also
have a protecting influence.2 As with other ferments, the
concentration of the acid-proteinase itself in a pure solution
influences the temperature at which it is most rapidly
destroyed.

When natural or artificial gastric juice (a solution of acid-
proteinase in dilute hydrochloric acid) is allowed to act upon
a protein, such as fibrin, the following changes are observed.
The fibrin begins to swell and its superficial portions become
translucent, until, under favorable conditions of temperature,
the insoluble protein is rendered soluble. If given time
enough, the acid alone will bring about a solution of the fibrin;
but if acid-proteinase is present this change occurs much more
rapidly. If the enzyme is employed in a neutral solution the
protein is not dissolved. Acid and ferment together are
therefore necessary to bring about the rapid change from the
protein to the soluble product. The soluble product consists,
as will be seen presently, of a mixture of a number of chemical
substances, which are distinguished from the original protein
upon which the acid-proteinase acted by their ready solubility
in water and their ready diffusibility through animal and
vegetable membranes. These properties, it will be noticed,

iv. Wittich: Pfluger's Arch., 1869, II, p. 193; ibid., 1870, III,
p. 339.

2 Biernacki. Zeitschr. fur Biol., 1892, XXVIII, p. 453.

ACTIOS OF THE ENZYMES. 121

stand in marked contrasl to those of the original protein sub-
stance— for instance, fibrin — which is insoluble and readily
held back by a filter or animal membrane. It is those prop-
erties of the products of gastric digestion which give them the
] tower of being easily taken up by the mucous membrane of
the alimentary tract.

Our conceptions of the nature of the products formed when
proteins are digested in the presence of acid-proteinase have,
within the last few years, been markedly altered, more espe-
cially through the investigations of Zunz,1 Pfaundler,2 Law-
row,3 Malfatti,4 Salaskin,5 Langstein,6 Emil Fischer 7
and Abderhalden.7 The work of all these authors indicates
that acid-proteinase working in the presence of an acid causes
a cleavage of the protein molecule into substances of a much
simpler chemical composition than we formerly supposed.
Where we once believed that proteoses and "peptones," in
the sense in which Kuhne used this term, constituted the
final products of gastric digestion, we now know that a large
number of substances, which were formerly looked upon as
produced only in pancreatic digestion, are also formed. In
experiments in which acid and acid-proteinase have been
allowed to act long enough, there have been found, besides the
more complex proteoses and "peptones," the following simple
compounds: leucin, tyrosin, alanin, phenylalanin, amino-

1 Zunz: Zeitschrift fur physiologische Chemie, 1899, XXVIII, p. 132.

2 Pfaundler. Zeitschrift fur physio logische Chemie, 1900, XXX,
p. 90.

3 Lawrow: Zeitschrift fur physiologische Chemie, 1899, XXVI, p.
513; ibid., 1901, XXXIIl,p. 312.

1 Malfatti: Zeitschrift fur physiologische Chemie, 1900, XXXI, p.
43.

6 Salaskin: Zeitschrift fur physiologische Chemie, 1901, XXXII, p.
592.

"Langstein: Hofmeister's Beitrage zur chemischen Physiologic,
1901, I. !«. .107.

' Kmil Fisoheh and A i-.ki i,ii \ i.mkn . Zeitschrift fur physiologische
Chemie, 1903, XXXIX, p. 81.

122 PHYSIOLOGY OF ALIMENTATION.

valerianic acid, aspartic acid, glutamic acid, and lysin. It
will be seen later that these compounds are the same as
those formed in the action of alkali-proteinase (trypsin) on
protein, and we must in consequence ascribe to the gastric
juice much greater digestive importance so far as the proteins
are concerned than heretofore.

An essential difference exists, however, in the velocity
with which the two enzymes bring about the decomposition
of protein into these simpler substances, alkali-proteinase
acting much more rapidly than acid-proteinase. The degree
of the splitting is also different in the two, trypsin causing
the total cleavage of much more of the original protein
than pepsin. Trypsin must, therefore, generally speaking,
be considered the more powerful of the two ferments.

5. Alkali-proteinase (trypsin) is the term applied to the
proteolytic enzyme found in the pancreatic juice and in a
large number of tissues, not only of the human being, but
other animals as well. The ferment was discovered by
Claude Bernard in the middle of the last century, and has
since then served as an object of study to scores of investiga-
tors. The ferment is present in the pancreatic juice of the
human foetus from before birth. Absolutely pure alkali-pro-
teinase has never been prepared, and even relatively pure
preparations are not easy to obtain. Simple extraction of
the fresh, finely minced gland with a saturated sodium chlo-
ride solution gives a very active preparation. Extraction of
the gland with chloroform water for several days has been
recommended by Salkowski. Very active and stabile alco-
holic and glycerine extracts of the proteolytic enzyme can
also be prepared. Mays l has studied the problem very
carefully, and has perhaps gotten the purest trypsin thus far
obtained. For the details of his method the original must
be consulted. While pancreatic juice obtained from a pan-
creatic fistula contains other ferments besides alkali-pro-

1 Mays: Zeitschr. fur physiologische Chemie. 1903, XXXVIII, p. 428.

ACTION OF Till: ENZYMES. 123

teinase, it contains none of the ordinary intracellular ferments
present in simple extracts of the gland itself. Pancreatic
juice obtained by Pawlovv's or some similar method repre-
sents, therefore, an excellent solution with which to study
the activities of the alkali-proteinase.

Alkali-proteinase will act in an alkaline, neutral, or even
faintly acid medium. The medium acting most favorably has
an alkaline reaction. Kanitz,1 who has recently investigated
this problem, states that the action of the enzyme is largely
independent of the nature of the alkali or alkaline salt used to
obtain the alkaline reaction, and is determined solely by the
number of hydroxy 1 ions present in the solution. A 1/200
to 1/70 normal solution of the alkali in regard to the hydroxyl
ions is the optimum one. An alkalinity greater than this
acts deleteriously upon the enzyme. The ferment acts very
well in a neutral medium, but is rapidly destroyed in the
presence of an acid, even of the concentration of the hydro-
chloric acid of the gastric juice.

The nature of the protein upon which alkali-proteinase
acts is not without influence upon the rapidity of the splitting
process. ' Unboiled fibrin cannot well be used in making
comparative tests with trypsin, as it is too rapidty digested.
Boiled fibrin is digested more slowly, and this substance,
or boiled white of egg, is ordinarily used in work on tins
ferment. Even the last-named is rapidly digested by alkali-
proteinase. The protein acted upon does not first swell,
as is the case with acid-proteinase, but breaks up at once
into small particles which rapidly go into solution.

Alkali-proteinase is very sensitive to temperature. It acts
best at about 40° C, being rapidly destroyed above this
point. Below 40° C. the activity of the enzyme falls off
gradually, but it is still recognizable even :ii 0° C. 70° C.
is ordinarily given as the highest temperature at which
alkali-proteinase will exhibit any proteolytic activity.

1 Kanitz. Zeitschr. i'. physiol. Chem., L902, XXXVII, i>. 7."..

124 PHYSIOLOGY OF ALIMENTATION.

Alkali-proteinase shows, in common with other ferments,
an increase in the velocity of reaction with an increase in the
concentration of the enzyme. This holds true, however,
only within certain limits of time, concentration of both
enzyme and protein, etc. In infinite time a small amount
of the ferment will bring about as much protein digestion
as a larger one. In no case is all the protein split into the
digestion products to be discussed below. Unless the
products of digestion are removed as soon as formed the
proteolysis is incomplete, or, as it is ordinarily put, an
accumulation of the products of digestion interferes with the
further action of the enzyme. This is probably due to the
fact that the activity of the enzyme is reversible. When the
products of the protein digestion are removed by dialysis as
soon as formed, a small amount of the enzyme will split an
indefinite amount of the protein.

When alkali-proteinase is allowed to act upon proteins,
the protein molecule is broken up into a number of simpler
substances. According to the generally accepted view, the
decomposition of the protein is brought about by a series of
successive cleavages. Shortly after the ferment has begun
its work, there can be recognized the proteoses, and later
the peptones, in the sense in which Kuhne used these terms.
Before the ultimate products of tryptic digestion are reached,
substances which in their chemical complexity stand between
them and the peptones, the peptides of Emil Fischer and
Abderhalden,1 are formed. These peptides represent com-
binations of amino-acids, and depending upon whether two,
three, four, or many molecules of the same or different
amino-acids enter into the composition of the peptide, we
distinguish between di-, tri-, tetra-, and polypeptide bodies.
The ultimate products of tryptic digestion are mono- and

1 Emil Fischer and Abderhalden: Zeitschrift fur physiologische
Chemie, 1903, XXXIX, p. 81; Abderhalden: Lehrbuch d. physiol.
Chemie, Berlin, 1906, Eiweissstoffe.

ACTION OF THE ENZYMES. 125

diamino-acids, many in number and differing markedly from
the protein itself or any of the intermediate products. In
*,he passage from the proteins to the ultimate digestion
products we find that the substances become progressively
more simple. Physically we pass from those which are
typical colloids, that is to say, amorphous substances with
high molecular weights, practically no diffusibility, and no
osmotic pressure, to crystalline bodies of a low molecular
weight and of a ready diffusibility. Whereas the original
substances are insoluble or only slightly soluble, the ultimate
products are, generally speaking, freely soluble. Qualita-
tively, the digestion under the influence of alkali-proteinase
does not differ materially from that under acid-proteinase;
quantitatively, alkali-proteinase is the more powerful enzyme,
producing the substances to be enumerated below much more
rapidly and in greater quantities than when acid-proteinase
is used.

In order to obtain the end products of alkali-proteinase
digestion for study, it is best to allow pure pancreatic juice
obtained from a Pawlow pancreatic fistula to act upon a
protein, such as fibrin. The mixture is covered with toluol
or some other antiseptic which prevents the development
of bacteria but does not interfere with the activity of the
alkali-proteinase, and the whole is kept at a suitable tem-
perature for varying periods of time. Many of the products
of alkali-proteinase digestion can be found shortly after the
ferment has been allowed to act upon the protein, but cer-
tain of the rare products cannot be found insufficient quan-
tities until the reaction mixture has been allowed to stand
even for months. In order to get a conception of the quan-
titative relations between the various digestion products .it
any desired time, the action of the ferment can be stopped
by boiling the reaction mixture. Frequently the autodiges-
tion of the pancreas and other organs has been used for the
study of the products of alkali-proteinase digestion, hut in
these cases it cannot be said with certainty that some of

126 PHYSIOLOGY OF ALIMENTATION.

he products formed are due to the action of alkali-proteinase
alone and not to the action of intracellular enzymes exist-
ing beside the alkali-proteinase.

The following is a list of the amino-acids that have been
isolated from various proteins. In spite of the great physi-
cal differences between the proteins obtained from different
sources, they are very similar in chemical constitution. When
any protein is split hydrolytically, be this under the influence
of alkali-proteinase or acid-proteinase, or as it is often accom-
plished in the laboratory, through the action of strong acids
or alkalies, the same series of simple substances is always ob-
tained which consists almost entirely of amino-acids. All
proteins, moreover, yield the same amino-acids, only the pro-
portion which these bear to each other in the different pro-
teins is different, and sometimes one or the other of the
acids may be entirely absent. In order to render what is to
follow more intelligible, the next paragraph contains a list
of the amino-acids which have been obtained not only through
the action of alkali-proteinase, but also by other methods of
hydrolysis. Most of these acids have, however, been isolated
from at least certain proteins through the action of alkali-
proteinase alone. It will be noticed that certain of those
enumerated have already been mentioned as products of
peptic digestion.

Glycocoll, alanin, aminoisovalerianic acid, leucin, isoleucin,
serin, aspartic acid, glutamic acid, lysin, arginin, histidin,
cystin, phenylalanin, tyrosin, prolin, oxyprolin, tryptophan.1

The diamino-acids in the above series, such as lysin, arginin,
and histidin, are often spoken of as the hexone bases, and con-
stitute with ammonia the basic products of the hydrolysis of
proteins.

The following diagram, as arranged by Abderhalden, may
serve to indicate the scheme according to which the proteins
are under the influence of a ferment (or other hydrolytic

1 Abderhalden. Lehrbuch d. physio). Chemie. Berhn, 1906, p. 160.

ACTIOX OF THE ENZYMES

127

- -z rt

Qr

r-

GO C • - -

i\-d 1

o

< 'Z a

1

o
.5

— c c

_ — c

128 PHYSIOLOGY OF ALIMENTATION.

agent) broken into successively simpler compounds until the
amino-acids are finally reached. From the albumins, for
example, are derived first of all the album oses, which may well
be looked upon as being made up of long chains of amino-
acids. These now break up into shorter chains constituting
the peptones. In the analysis of albumin we are able to
recognize this stage in digestion by the appearance of certain
color reactions (biuret test), which it will be seen later l are
given by certain polypeptides which have been produced syn-
thetically. The peptones may therefore be looked upon as a
mixture of polypeptides. These polypeptides now break up
into still simpler chains of amino-acids passing more or less
directly through the stages of hexa-, penta-, tetra-, etc., pep-
tides until the simple mono- and diamino-acids are reached.
The peptides giving a biuret test pass over without a break
into those which do not give this reaction. It is clear, there-
fore, that little by little the name "peptone" must disappear
to give way to well-defined chemical compounds. Transitional
forms of all degrees of chemical complexity exist between the
peptones on the one hand and the simple amino-acids on the
other. The diagram does not show, of course, the way in
which any protein is hydrolyzed, but rather one or two
schemes according to which this may occur.2

1 See p. 142.

2 Abderhalden: Lehrbuch d. physiol. Chemie, Berlin, 1906, p. 206.

CHAPTER VII.

THE ACTION OF THE ENZYMES FOUND IN THE HUMAN
ALIMENTARY TRACT (Continued).

6. The Recognition and Quantitative Estimation of the
Proteinases. — The methods which have been devised for the
qualitative recognition of the proteolytic ferments consist for
the most part in an exposure of a readily obtainable protein,
such as fibrin from blood or white of egg to an extract of the
animal or vegetable organ which is being tested, and "finding
that this is dissolved. Care must be taken in each case, of
course, to provide, through the addition of an acid or an alkali
to the mixture, an acid, neutral or alkaline reaction depending
upon whether acid-, ampho-, or alkali-proteinase (pepsin,
papain, or trypsin) is being tested for. Instead of utilizing
the disappearance of the protein as evidence of the presence
of a proteolytic ferment, the appearance in the reaction mix-
ture of certain well-established products of proteolytic activity
may also be used. Since acids, for example, can by them-
selves bring about the destruction of a protein (but only after
a long time at ordinary temperatures), the time element also
plays a role in these qualitative tests, in that the destruction
of the protein and the appearance of digestion products must
occur within a relatively short time. The actual time con-
sumed in bringing about the total solution of a given amount
of protein may therefore be used as an index to the amount
of ferment present, a larger amount of ferment, under other-
wise similar conditions, bringing about a total digestion more
rapidly than a smaller one.

129

130 PHYSIOLOGY OF ALIMENTATION.

The methods which have been devised for the quantitative
estimation of proteolytic ferments are various and still
exceedingly unsatisfactory. For the most part, no absolute
but only comparative estimations of the ferment content of
any organ or secretion can be made. As with the other fer-
ments, it is not possible to obtain the proteolytic ferments in
anything even approximating a pure state without tremendous
and incalculable loss, so that direct estimations are out of the
question. We have to content ourselves therefore with com-
parative studies, in which we can say a definite mixture
digests a chosen quantity of a protein more or less rapidly
than an arbitrarily established standard. From the degree
of difference we can get some idea of the relative amounts of
proteolytic ferment present in the different reaction tubes, but
this only within certain well-defined limits of time and limits
of concentration of ferment and protein. Of the various
methods and their modifications which have been devised
from time to time for the quantitative estimation of pro-
teolytic ferments, only those are mentioned of which an under-
standing is necessary for what is to follow in this volume.

(a) Griltzner's 1 Method. — This is a colorimetric method in
which fibrin from ox-blood is used. The fibrin obtained by
whipping fresh blood is finely chopped and washed in water,
after which it is stained in a carmine solution. After another
thorough washing in water this carmine-stained fibrin is pre-
served in glycerine. When a test is to be made the colored
fibrin is thoroughly washed in water and a weighed amount
introduced into each of the digestion mixtures to be' tested.
As the fibrin is digested the reaction mixture is colored red,
from the depth of which, when compared with an arbitrarily
established scale, deductions can be made regarding the rela-
tive digestive power of the different mixtures.

(b) Mett's Method consists in a determination of the amount
of coagulated egg albumin digested out of capillary tubes.

1 Grutzner: Pfluger's Archiv, 1874, VIII, p. 452.

ACTION OF THE ENZYMES. 131

Glass tubes 1 to 2 mm. in diameter arc drawn full of fresh
white of egg and dipped for exactly a minute into water
having a temperature of 95° C, in which the albumin coagu-
lates. After the tube has been allowed to cool slowly it is
cut into short pieces and these are dropped into the digestion
mixtures to be studied. The number of millimeters of em-
ulate digested out of the tube is determined by the help
of a low-power microscope and scale from which the digestive
power of one mixture as compared with that of another may
be determined. According to a principle first declared by
Schutz the amount of proteolytic ferment present in the
various reaction mixtures is proportional not to the number
of millimeters of albumin digested out of the tubes but to
their square. A digestion mixture which dissolves 2 mm. of
albumin out of a tube is supposed to contain not twice as much
proteolytic ferment as one which digests only 1 mm. out of
a tube, but four times as much.

Mett's method, though exceedingly simple, is by no means
free from error.

(c) Spriggs' Method. — Spriggs 1 has devised a method for
determining quantitatively the rate at which a coagulable
protein is digested under the influence of different proteolytic
ferments which for simplicity and accuracy is far superior
to the ordinary methods employed for this purpose. Spriggs'
method takes advantage of a physical change — a decrease in
viscosity which occurs in a protein solution when this is acted
upon by a proteolytic ferment. In order to measure this
change in viscosity use is made of the viscosimeter of Ostwald,
illustrated in Fig. 19a, which allows an experimenter to deter-
mine accurately the time required for a measure* 1 amount
of liquid contained in A to flow through the capillary tube
B into C. The greater the viscosity, the greater, of course,
will be the time required for a liquid to flow Through the
capillary tube.

'Spriggs: Zeitschr. f. physiol. Chem., L902, XXXV, p. 165.

132

PHYSIOLOGY OF ALIMENTATION.

With the use of such an instrument Spriggs found that
during digestion the viscosity of a solution of a coagulable
protein gradually decreases. This decrease in viscosity
corresponds with a chemical change in the protein undergoing
digestion from the state in which it is coagulable by heat

V

^^B

2
Hour

(b)

Fig. 19.

into that in which it is not coagulable by this means, — in
other words (to speak not very accurately), from the albu-
mins into the peptones.

If the change in the viscosity of the protein undergoing
digestion is expressed in the form of a curve, one similar to
that shown in Fig. 19 (6) is obtained. As can readily be seen,
the viscosity of the protein solution decreases at first very
rapidly, later more slowly, until finally it runs almost parallel
with the base-line. When this line of unchanging viscosity
is reached, the larger part of the coagulable protein has
been converted into the uncoagulable.

ACTION OF THE ENZYMES. 133

The curve representing the decrease in the viscosity of a

protein solution can be expressed mathematically when it
becomes possible to calculate the relations which exist be-
tween the velocity of digestion and the amount of pro-
teolytic ferment present.

7. Antiproteinase (antipepsin and antitrypsin). — Under the
heading antiproteinase we understand a substance discovered
by Weinland,1 which has the power of markedly inhibiting
by its presence the action of the proteolytic enzymes. Anti-
proteinase is therefore one of the so-called antiferments.
Antiproteinase can be obtained from a number of sources —
the mucous membrane of the stomach and intestines, but,
best of all, from various intestinal worms, especially ascaris.
A description of the method by which antiproteinase can be
obtained from ascaris will suffice to indicate the method by
which, in general, this substance can be obtained from any of
the tissues or fluids in which it is present (see below).

A very active though impure preparation of antiproteinase
can be obtained by simply grinding up a number of the intes-
tinal worms with quartz sand. The addition of this ground-up
mass to an acid-proteinase or alkali-proteinase solution
markedly inhibits the activity of these ferments. A better
preparation of the antiproteinase can be obtained by sub-
jecting the ascaris paste to great pressure and collecting
and filtering the fluid which is squeezed out. The anti-
ferment contained in this very active juice can be further
purified by adding alcohol to it, whereby the antiproteinase is
precipitated as soon as the concentration of the alcohol in the
mixture exceeds 85 percent. The substances (impurities)
which are precipitated before the concentration of the alcohol
reaches 60 percent may be filtered off without danger of
losing the antiproteinase. The precipitate of antiproteinase
brought down by the So percent alcohol settles to the bottom

'Weinland: Zeitschr. f. Biologie, L902, XLIV, p. 1; ibid., 1902,
XLIV, p. 45.

134 PHYSIOLOGY OF ALIMENTATION,

and may at the end of twenty-four hours be filtered off.
After washing in 96 percent, then 100 percent alcohol, and
finally with ether, the precipitate is dried over sulphuric acid.

The antiproteinase obtained in this way is a somewhat
sticky powder which is readily soluble in water, and which is
still contaminated with some impurities. The isolation of the
antiferment is accompanied by a falling off in its activity.
The activity of the alcohol-precipitated antiproteinase when
redissolved in water is less than half that of the original juice
obtained from extraction of the ground-up worms.

The following experiments carried out with fibrin obtained
from pig's blood, which is exceedingly sensitive toward pro-
teolytic ferments, may serve to show how markedly anti-
proteinase inhibits the action of alkali- and acid-proteinase.

Exp. A. Two tubes each containing 8 c.c. water, 0.04 gm. sodium
carbonate, 0.015 gm. alkali proteinase, and several pieces of fibrin, but
the one in addition 7 c.c. of ascaris extract, the other an equal amount
of water, are both put into the incubator at 37° C. At the end of two
hours the fibrin in the tube containing no ascaris extract (antiprotein-
ase) has entirely disappeared. The fibrin in the tube containing the
antiproteinase is still entirely unchanged after six days, and even on
the eleventh day of the experiment one-third of the fibrin is still un-
digested.

Exp. B. Two tubes each containing 7 c.c. water, 0.23 gm. hydro-
chloric acid, 0.015 gm. acid-proteinase, and several pieces of fibrin, but
the one 8 c.c. of ascaris extract, the other an equal amount of water,
are put into the incubator at 37° C. The fibrin in the tube contain-
ing no antiproteinase is dissolved at the end of one hour. The fibrin
in the tube containing the ascaris extract is unchanged on the fourth
day, and on the ninth day only a trace of the fibrin seems to have been
dissolved.

Antiproteinase is comparatively sensitive toward heat.
Boiling for one and a half minutes suffices to entirety do away
with the protective properties of an ascaris extract. Heating
for ten minutes to 60° C. does not injure the antiproteinase,
but heating for the same length of time to 80° C. reduces its

ACTION OF THE ENZYMES. 135

activity markedly. If the ascaris extract is kepi at {.)5° C.
for ten minutes, it has lost its protective power altogether.

At ordinary room temperature ascaris extract keeps very
well when 1 to 2 percent of sodium fluoride have been added
to it to prevent the development of bacteria. Under these
conditions Weinland has kept an extract for eight months
without apparent loss in the power of the juice to inhibit the
action of proteolytic enzymes.

We have in the foregoing paragraphs spoken of antipro-
teinase as though it were a single substance. It is possible
that there exist several antiproteinases, though this question
is still unsettled. It may be that there exists an antialkali-
proteinase (antitrypsin) and an antiacid-proteinase (anti-
pepsin), but further experiments must be made to settle this
point definitely.

8. Why the Alimentary Tract Does Not Digest Itself. —
Weinland 's discovery of antiproteinase (antipepsin and anti-
trypsin) is of fundamental physiological importance, giving
us, as it does, a partial explanation of the immunity which
"living " tissues possess towards the proteolytic enzymes. It
is a well-known fact, for example, that the intestinal worms —
nematodes, trematodes, cestodes, etc. — are not acted upon
by the secretions of the stomach, pancreas, and small intes-
tine, which so readily and rapidly bring about the digestion
of the ordinary proteins that enter the alimentary tract as
food. In the same way we know that cysticerci, the larvae
of tapeworms, must pass through the stomach in order to
get into the intestine, where they develop into the adult
animals. In this passage through the stomach they are sub-
jected to the action of the gastric juice; this digests the sac
in which the larva is contained, as well as the body of the
larva, the head and neck only being able to pass on undigested
into the intestine. From these fragments the adult develops,
and this in spite of the fact that the growing animal is daily
bathed in streams of intestinal contents which are charged
with most active proteolytic enzymes. We know that a

136 PHYSIOLOGY OF ALIMENTATION.

tapeworm may exist for months, even years, in the intestine
of a man or other animal.

Similarly mysterious has appeared to us the immunity
which both the stomach and small intestine possess against
their own secretions. The stomach is not digested by the
gastric juice, nor the duodenum when the pylorus opens.
Neither is any portion of the small or large intestine, under
normal circumstances, acted upon by the pancreatic juice
which passes through it.

The hypotheses which have been proposed from time to time
to explain this immunity of intestinal parasites and alimen-
tary tract have been many and, for the most part, of a vital-
istic nature. Claude Bernard believed that the epithelial
covering of the intestinal tract protected the underlying tissues
from digestion, but this idea, besides explaining nothing ;
stands in contradiction to the facts of pathology, which show
that the absence of epithelial covering (for instance, in ulcers
of the gastro-intestinal tract from any cause whatsoever) is
by no means always, in fact only at times, accompanied by a
loss of the underlying muscular or other tissues. These sub-
epithelial structures are therefore just as immune against
digestion as the epithelium itself.

Nor can Pavy's theory, which assumes that the stomach is
not digested because it is protected through the alkalinity
of the blood, be looked upon as any more serviceable. The
blood is, first of all, not alkaline, but neutral in reaction, and,
secondly, Pavy's explanation is of no value when we deal
with the intestine, the contents of which at no time possess
the decided acid properties of those of the stomach and are
at times perhaps even alkaline. The remaining theories
which have been proposed from time to time need not be dis-
cussed, for they have almost without exception covered up
the problem at hand by attributing to the intact mucosa
"living" properties which we could never hope to find in
"dead" matter. As is well known, the "dead" mucosa
of the stomach undergoes partial digestion^ as seen in

ACTION OF Till: ENZYMES. 137

the post-mortem excoriations of the gastric mucous mem-
brane.

Weinland's experiments give us a ready explanation of the
long-well-established facts which have been outlined. The
mucous membrane of the stomach and intestine contains

antiproteinase; so also do the adult intestinal worms. In
the case of the cysticerci only the head and neck of the
larvae contain antiproteinase, in consequence of which the
remaining portions of the young parasites are digested. In
the same way we may assume that the greater ease with
which cooked meats are digested than raw, is due, in part at
least, to the fact that in them the antiproteinase is destroyed
by the heat used in preparing the meat.

Many facts indicate that antiproteinase is widely dis-
tributed throughout the body, being present in probably
all tissues with the exception of the purely fatty ones. It
is entirely probable that antiproteinase exists also in the
insectivorous plants, which through their proteolytic secre-
tions are able to digest the animals they have caught without
being acted upon by these secretions themselves. That
"living" organs, such as the spleen, when introduced into the
stomach are able to withstand the action of the gastric juice
is dependent upon the presence of antiproteinase in these
organs. In the same way, extracts of liver and muscle are
able to decrease markedly the digestive activity of acid-
proteinase, which indicates that antiproteinase is present
in them. The same is true of blood-serum and red blood-
corpuscles. The discovery that antiproteinase exists in the
liquid portion of the blood seems to indicate that this ferment
must exist in every part of the body.

Without discussing the subject more fully, which would
take us too far afield, it may not be amiss to point out what
an important physiological nMc this universal distribution
of the antiproteinase must play, and what pathological con-
sequences may accompany its hick or overproduction when
it is remembered that proteolytic ferments (acid- and alkali-

133 PHYSIOLOGY OF ALIMENTATION.

proteinase) are found in practically every tissue of the body
A change in the proper balance between ferments and anti-
ferments can easily be imagined to be accompanied by pro-
found changes in the activities of any organ.

The probable role which a lack of antiferment can play
in the production of gastric and intestinal ulcers deserves
special mention. It is readily apparent from what has gone
before that if the stomach, for example, does not digest
itself because the mucosa contains antiacid-proteinase, a
lack of this protective principle would allow the gastric
secretion to take effect upon the mucosa as well as upon any
food which passes through the stomach. What holds for the
stomach is true of the intestinal tract in general. In the
absence of experiments regarding this point, it is useless to
discuss the causes which might lead to such a lack of anti-
ferment in different portions of the alimentary tract. A
large number of toxic causes can be imagined as capable of
so interfering with the normal activity of the alimentary
mucous membrane as to lead to an inadequate production
of antiproteinase, or none at all. That bacterial toxins
and various mineral poisons are capable of producing ulcera-
tions of the gastro-intestinal tract is a well-known fact.
Whether all or some of them act as indicated could readily
be determined by experiment.

Special mention must be made of the round ulcers of the
stomach. In these cases the general pathological blood
condition so often found in these cases might be the pre-
disposing condition which favors the inadequate production
of antiproteinase in certain regions of the stomach. Some
authors have expressed the view that an occlusion of the blood-
supply of circumscribed areas of mucous membrane in the
stomach lies at the basis of round ulcers in this viscus. It
is certainly true that an experimental occlusion of the artery
supplying the mucous membrane of the stomach or intestine
is almost constantly followed by an ulcer. The lack of
blood-supply would in this case have to be looked upon as the

ACTION OF THE ENZYMES. 139

cause which led to the injury of the cells of the mucous
membrane, which, with their consequent inadequate supply
of antiproteinase, were digested by the proteolytic ferments
present in the alimentary tract.

In cases of round ulcer of the stomach yet another factor
besides lack of antiproteinase plays a rule in the production
of the lesion, namely, a hyperacidity of the gastric juice.
While this hyperacidity has by several authors been looked
upon as being involved in the etiology of round ulcer, just
how it was involved could not be said. The experiments of
Weinland give us a clue. While antiproteinase is able to
protect fibrin against digestion by a pepsin-hydrochloric
acid mixture, it is able to do so only within certain limits
of concentration of the hydrochloric acid. When the con-
centration of the hydrochloric acid exceeds a certain point
the antiproteinase is only partially able to inhibit the action
of the acid-proteinase, so that the fibrin slowly goes into
solution. We can imagine the hyperacidity of patients
affected with round ulcer to play a similar role, in that the
excessive acid present prevents the antiproteinase from
adequately protecting the stomach-wall. But the hyper-
acidity can by no means be considered even the chief etio-
logical factor, for if it were, gastric ulcers should be diffuse
affairs, while they are instead more or less localized and
often intimately connected with local vascular disturbances.
The resistance which the submucous tissues of the alimen-
tary tract (such as the musculature) usually offer to the
digestive fluids that bathe them must also be attributed to
the presence of antiproteinase in them. In harmony with
this idea we must also assume that when the ulceration of
the alimentary tract extends beyond the mucosa the involved
tissues have first been rendered susceptible by causes which
lead to the presence of an inadequate supply of the anti-
ferment.

The parallelism which exists between the proteinases and
antiproteinases on the one hand, and the toxins and antitoxins

140 PHYSIOLOGY OF ALIMENTATION.

on the other, will occur to every one. The mucous mem-
brane of the* alimentary tract is, by virtue of its contained
antiproteinase, "immune" against the "toxic" proteinases
which daily pass over it.

A second reason why the tissues of the alimentary tract
as well as the tissues of the body in general, are not acted
upon by the ferments present in them may reside in the
chemical constitution of the substances making up the cells
themselves. As Abderhalden1 has pointed out, the different
proteins contained in an organ are by no means acted upon
by the proteinases with the same ease. The substances mak-
ing up the connective tissues, such as elastin and spongin for
example, are acted upon scarcely at all by a pepsin-hydro-
chloric acid mixture or trypsin. This property is connected
with the chemical constitution of the substances concerned,
which contain those amino-acids in largest amounts whose
presence offers the greatest resistance to hydrolysis of the
protein molecule. It might well be possible, therefore, that
living cells are endowed with properties which enable them to
so modify the proteins absorbed by them as to render them in-
capable of being acted upon by the ferments contained in the
cells. Only a very slight change in the chemical constitution
of a compound will make it impossible for a ferment to attack
it, for, as is well known, the ferments are dependent in a
most limited way upon the stereochemical construction of
the molecules upon which they are capable of acting.

9. On the Reversible Action of the Proteinases. — The
question of the means by which the simple digestion-prod-
ucts of the proteins are again built up into the complicated
albumins, globulins, etc., which we find in the organism has
within the last few years been much debated. Of first in-
terest in this connection are the researches of Emil Fischer,2-

' Abderhalden: Lehrbuch d. physiol. Chemie, Berlin, 1906, p. 510.

2 Emil Fischer: Berichte d. d. chem. Gesellsch., 1906, XXIX, p. 530,
where references to the individual papers of the author will be
found.

ACTION OF THE ENZYMES. 141

and with him of Emil Abderhalden1 and their pupils, on the

chemical synthesis of proteins. Even though no more than
perhaps a few of the methods employed by these workers
to bring about these syntheses arc of a character which we
c:ut imagine as possible within living cells, this work must
for all time furnish the foundation upon which further ad-
vances in the chemistry and physiology of the proteins must
build.

Proceeding on the hypothesis that the protein molecule rep-
resents a long series of amino-acids chemically joined to each
other in various combinations, Emil Eischer showed that it is
possible to link two or more amino-acids together and obtain
a series of chemically more complex compounds known as
'peptides. If, for example, one molecule of glycocoll is com-
bined with a second molecule of the same substance the
dipeptide glycyl-glycin is obtained. In a similar way leucyl-
leucin can be obtained through the union of two molecules
of leucin, and alanyl-alanin from the union of two of alanin.
All these are dipeptides. It is possible, however, to make
three, four, five, six, etc., amino-acid molecules enter into
chemical combination with each other and so obtain tri-,
tetra-, penta-, hexa-, or polypeptides. A large number of
such peptides have been prepared, as examples of which the
following may be cited: 2

Dipeptides: Glycyl-alanin, alanyl-glycin, alanyl-leucin,
leucyl-glycin, glycyl-tyrosin, leucyl-prolin, etc.

Tripeptides : Leucyl-glycyl-glycin, leucyl-alanyl-alanin.

Tetrapeptides: Tetraglycin, dileucyl-glycyl-glycin, dialanyl-
cystin.

Pentapeptides : Pentaglycin, leucyl-tetraglycin.

The means by which such syntheses are accomplished are
various, and the number of combinations possible very great.
Let us ask now whether they are of more than chemical in-

1 See Abdekhalden's excellent Lehrbuch d. physiol. Chenrie, Berlin,
190<), Eiweissstoffe.

2 Abdeuhalden: 1. c., p. 19G.

142 PHYSIOLOGY OF ALIMENTATION.

terest, and whether they actually represent combinations of
amino-acids such as are produced in the action of ferments
or acids on proteins of various kinds.

That such is the case can be shown first of all by certain
chemical tests. In the analysis of proteins we encounter a
group of substances ordinarily called peptones, which are
characterized by their power of giving certain reactions such
as the biuret test. It is of great interest, therefore, that
many of the peptides which have been produced synthetically
also give the biuret test. While the dipeptide glycyl-glycin
and the tripeptide triglycin give no biuret reaction, this is
positive with the tetrapeptide tetraglycin. Dialanylcystin
gives a biuret reaction, while the higher peptides containing
seven and more amino-acids in the molecule, such as leucyl-
pentaglycin, give a red biuret test which seems identical
with that given by the peptones derived from silk. Phos-
photungstic acid, which is abundantly used as a precipitant
for the simple digestion-products of proteins, will also precipi-
tate many of the synthetic peptides. Certain of the amino-
acids which are only difficultly soluble in water yield peptides
which are readily soluble. The reverse is often observed in
the analysis of proteins. When, moreover, amino-acids hav-
ing a sweet taste are joined together chemically they yield
substances having a bitter taste. It is a well-known fact
that the ordinary peptones have a bitter taste.

Certain of the peptides which have been artificially produced
can be split into amino-acids by pancreatic juice in the same
way as the peptides formed in an ordinary digestion mixture.1

With these remarks on the synthesis from amino-acids of
substances which seem to agree in their chemical and biologi-
cal character with the peptones we will try to see if there is
any experimental evidence at hand to indicate that from
substances standing close to the class of peptones others
giving the reactions of the albumins may be obtained. It

1 Abderhalden: 1. c, p. 201.

ACTIOS OF THE ESZYMES. 143

looks as though this further synthesis of albuminous sub-
stances has been accomplished and by means which we can
well imagine active in the living organism.

Of first interest in this direction is the work of Okouneff,
who, in 1S95, showed that through the action of trypsin on a
concentrated solution of proteoses the latter suffers a physi-
cal change in that flakes appear in it, or in that the whole
assumes a jelly-like consistency. This change in consist-
ency (increase in viscosity) has been shown to occur not only
under the influence of alkali-proteinase (trypsin), but also
acid -proteinase (pepsin) and ampho-proteinase (papain).
It is a change, therefore, which is brought about in a solu-
tion of proteoses by any of the ordinary so-called proteo-
lytic ferments.

What is the character of this change in viscosity? This
question has been investigated by a number of observers
from both a chemical and a physical standpoint, and the
results obtained by each indicate very strongly that the proc-
ess of the formation of "plastein," as the above is called,
represents a reversion, under the influence of the proteolytic
ferments, of proteoses into more complicated proteins. From
a chemical standpoint, proof in this direction has been brought
especially by Sawjalow,1 who has succeeded in obtaining
from a proteose solution upon which a proteolytic ferment
had been acting for some time, and which originally had been
free from this reaction, a coagulum on boiling after the addi-
tion of acetic acid. This is a reaction which, it is well known,
is considered characteristic of the albumins.

The change which occurs when "plastein" is formed has
been investigated from a physical standpoint by Herzog,2
and to him belongs the credit of recognizing in it the reversible
activity of a proteolytic ferment.

'Sawjalow: Pfliiger's Archiv, 1901, LXXXV, p. 171; Centralblatf
fur Physiologie, L903, XVI, p. 625.

■ IIeuzog. Zeitschrift fur physiologische Chemie, 1903, XXXIX, p.
305.

144 PHYSIOLOGY OF ALIMENTATION.

As proof that the formation of "plastein " indicates that a
proteolytic ferment has synthesized from the proteose solu-
tion a substance or substances which lie nearer the original
protein than the proteoses, the following may be said:

We became familiar on p. 131 with Spriggs' observation
that a protein solution undergoing digestion under the in-
fluence of acid-proteinase (pepsin) and hydrochloric acid
suffers a decrease in viscosity, and that this decrease occurs
rapidly at first and then more slowly. When a solution of
proteoses and peptones (ordinary commercial "peptone ")
has added to it an artificial gastric juice the mixture is found
to increase in viscosity, at first only slowly and then very
rapidly. We have, in other words, exactly the reverse of what
occurred before. This seems to justify the conclusion that
acid-proteinase (pepsin) is able not only to catalyze the
analysis of a protein but also to catalyze its synthesis from
the products of digestion. What has been said holds not
only for acid-proteinase (pepsin) but also for alkali- and
ampho-proteinase (trypsin and papain).

If the above is true and the formation of "plastein " is
really to be looked upon as representing a synthesis of
protein which occurs under the influence of a proteolytic
ferment, then we should expect that the same external con-
ditions which favor or hinder the activity of a proteolytic
ferment in hastening the analysis of a protein should favor
or hinder in the same way the activity of this ferment when
it is hastening the synthesis of a protein. Thanks to the
researches of Weiniand,1 we are familiar with a substance,
antiproteinase (antitrypsin, antipepsin) , which retards (prac-
tically prevents) most markedly the activities of the pro-
teolytic ferments. The addition of a small amount of
anti-proteinase, obtained, for example, from the body of the
intestinal worm ascaris, to a digestion mixture of protein and
proteolytic ferment practically prevents the latter from act-

1 See p. 133.

ACTION OF THE ENZYMES. 145

ing upon the protein. In the same way ascaris extract pre-
vents the synthesis of protein (formation of "plasiein") when
it is added in a corresponding amount to a reaction mixture
consisting of proteoses and a proteolytic ferment.

The constant association of a milk-curdling ferment with a
proteolytic ferment — the association of caseinase with acid-,
alkali-, and ampho-proteinase wherever these ferments have
been isolated — has given rise to the idea to which attention
has already been called elsewhere, that these two ferments are
united in a giant molecule, but that different portions of this
molecule have different activities. It is of interest, therefore,
to add in this connection that antiproteinase, which reduces
so markedly the proteolytic activity of the giant molecule,
does not affect its milk-curdling power.

CHAPTER VIII.

THE ACTION OF THE ENZYMES FOUND IN THE HUMAN
ALIMENTARY TRACT (Concluded).

io. Protease (erepsin). — The observation of Salvioli, Hof-
meister, Neumeister, and others that peptone solutions when
brought in contact with pieces of still living intestinal mucous
membrane no longer give a biuret reaction after the lapse of
some time, that is, disappear, has usually been interpreted
as evidence indicating that the small intestine has the power
of synthesizing protein from the products of protein digestion.
It has, in other words, been generally believed that the
peptones which are formed in the course of ordinary
digestion are built up again into more complex bodies — those
giving no biuret reaction — in their passage through the
intestinal wall. Within recent years Cohnheim 1 has re-
peated some of these older experiments, but in attempting
to find corroborative evidence for the ordinary explanation
by the discovery of a larger amount of coagulable protein
in the intestinal wall or its surrounding liquids after the biuret
reaction had disappeared from the peptone solution than
before, his endeavors proved unsuccessful. He found instead
that in place of an increase in the amount of coagulable
protein he really got an increase in the amount of crystalline
digestion-products as the biuret reaction disappeared. The
peptones which are formed in the course of ordinary diges-
tion when in contact with the living intestinal mucosa there-

1 Cohnheim: Zeitschr. f. physiol. Chemie, 1901, XXXIII, p. 451;
1902, XXXV, p. 134.

146

ACTION OF THE ENZYMES. I 17

fore disappear, not because they are synthesized into more
complex compounds, but because they are broken up into
simpler ones. A recognition of this fact led to the discov-
ery of protease (erepsin), to a discussion of the identifica-
tion and properties of which we shall now turn.

The proof that the change from peptone to the simple
crystalline compounds mentioned above occurs under the
influence of a ferment contained in the wall of the small
intestine can be shown very well by introducing into each of
two tubes a solution of peptones and several pieces of well-
washed intestinal mucous membrane from a freshly killed dog
or cat. One of the two tubes is then boiled, after which both
are set aside in an incubator at 39° C. for a number of hours.
While in the boiled tube the biuret reaction persists even if we
wait for days or weeks, it is found to become fainter and
fainter in the unboiled tube, until in the course of perhaps an
hour or two — depending upon the amount of peptone and in-
testinal mucous membrane originally present — the biuret
reaction disappears entirely. Hand in hand with this dis-
appearance of the biuret reaction goes an increase in the
amount of crystalline precipitate which may be obtained
upon the addition of suitable reagents, and to a discussion of
which we shall return immediately.

It is only necessary to add that this ferment, which the
above simple experiment has indicated exists in the mucous
membrane of the intestine, can be extracted from it. Simple
extraction with an alkaline physiological salt solution of the
intestinal mucous membrane, after it has been scraped from
the submucosa and thoroughly triturated in a mortar with
sand, suffices to yield a very active solution of the enzyme,
though, of course, not a very pure one. The same difficulties
which were found to exist in the preparation of the other
ferments in a pure state exist here also. By fractional
precipitation with ammonium sulphate much purer specimens
of the ferment may be obtained, but for the details of this
process the reader must consult the original.

148 PHYSIOLOGY OF ALIMENTATION.

We have now to discuss the character of the crystalline
products into which protease splits peptones. If a protease
solution obtained from dog's intestine, for example,, is added
to a solution of peptones (in Kuhne's sense), and the whole
is kept in an incubator at body temperature, it is found that
only a slight biuret reaction is obtained on the third or
fourth day from the reaction mixture which on the first day
gave an intense reaction. If, now, the digestion experiment
is continued a few days longer, the biuret reaction disappears
entirely, indicating that the peptones have been changed
into something else. This "something else" has been shown
to consist of leucin, tyrosin, lysin, histidin, arginin, and
ammonia, all of them substances therefore identical, quali-
tatively at least, with those obtained when alkali-proteinase
(trypsin) is allowed to act on a protein. The question may
therefore very justly be raised, Are we not perhaps really
dealing with the action of alkali-proteinase in an extract of
the small intestine? This question is to be answered in the
negative, and for the following reasons. Alkali-proteinase,
it is well known, acts upon a large number of the so-called
"native" proteins— for example, fibrin, white of egg, serum
albumin, etc. If proper precautions are taken to obtain a
protease solution free from alkali-proteinase this property
of acting on native proteins is lacking. Fibrin, for example,
which is acted upon so rapidly by alkali-proteinase that it
can scarcely be used in quantitative studies with this fer-
ment, may remain in a protease solution for days, even if the
fibrin has not been boiled, without showing any evidences
of having been attacked.

One of the ordinary "native" proteins is, however, acted
upon by protease, and that is the casein of milk. This
fact is of physiological importance, as the presence of protease
in the intestine renders one of the foods of infants capable
of digestion even when the ordinary proteolytic ferments
(acid- and alkali-proteinase) are lacking. Protease will act
also upon certain of the proteoses, but its activity manifests

ACTION OF THE ENZYMES. 1 10

itself par excellence upon the peptones. As the proteoses

constitute, with the exception already given, I lie chemically
most complex substances upon which Coiinheim's ferment
acts, it has been called protease.

Through the investigations of a number of authors, more
especially Vernon,1 we have become acquainted with the
presence of protease in other tissues besides the small intes-
tine. It is very probable that this fact will necessitate a
revision in our knowledge of the ultimate digestion-products
of alkali-proteinase, for the two ferments are frequently
present in the same tissues, and no doubt some of the sub-
stances which are to-day believed to have been produced
through the activity of the alkali-proteinase are really pro-
duced through the protease which is present simultaneously
and which has not been considered in the analyses at present
at hand. Of interest also in this connection is the fact that
the " Bence-Jones protein," which appears in the urine in
certain pathological states, is not acted upon by protease.
This seems to indicate that it does not belong to the pro-
teoses (albumoses), under which heading it is usually classi-
fied.

Protease, like other ferments, is markedly affected by the
character of the medium in which it is active. It acts best
in an alkaline medium, although it is still able to bring about
its characteristic effects in one having an acid reaction.

ii. Lipase. — Under the term lipase (steapsin) or the
lipases we understand those ferments that have the power
of acting upon neutral fats of various kinds and splitting
these into their constituent fatty acids and alcohols. The
earlier investigators believed that the formation of an emul-
sion from the fat represented one of the characteristic prop-
erties of lipase. This is not true, however. The distinguish-
ing property of lipase resides in its power of bringing about
not a physical but a chemical change1 in the fat. While we

1 Vernon: Journal of Physiology, 1904, XXXI 1 , p. 33.

150 PHYSIOLOGY OF ALIMENTATION.

are to-day acquainted with the presence of lipase in a large
variety of plant-cells, it is interesting that the discovery of
lipase was originally made in experiments on the physiology
of the pancreas. This organ contains large quantities of the
ferment, but it is well to remember that lipase is one of the
most widely distributed enzymes in the animal organism, oc-
curring in practically every organ of the mammal. The liver,
the stomach, the small intestine, the kidneys, the subcuta-
neous tissues, the mammary glands, the blood, and the lymph,
all contain lipase.

The fats of greatest physiological importance are all of
them esters of the triatomic alcohol glycerine with palmitic,
stearic, or oleic acids. These fats (known as palmitin, stearin,
and olein) take up water under the influence of lipase and
split into glycerine and fatty acid. A quantitative deter-
mination of the activity of a lipase may therefore be made
by ascertaining the amount of acid that is formed. Quali-
tatively the formation of the acid can be readily demon-
strated by the addition of an indicator to a mixture of fat and
lipase.

In laboratory studies with lipase, palmitin, stearin, and
olein are comparatively little used. Other esters are acted
upon more rapidly by the ferment, so that this property, in
addition to their ready solubility in water, renders them more
suitable for study. In this way monobutyrin, ethyl butyrate,
etc., have come to be extensively used.

Pure preparations of lipase have never been obtained.
The best rapidly lose in strength in the course of a few days,
even when most carefully protected. Ordinarily, simple
aqueous or NaCl-solution extracts are made of entirely fresh
organs which are minced and ground up in a mortar with
quartz sand. These extracts are then used for experimental
purposes. Glycerine extracts have also been prepared.

Lipase is, in the presence of water, exceedingly sensitive
to comparatively low temperatures. When dry, the lipase
from the castor-oil bean will stand a temperature above 100° C,

' ACTIOS OF THE ENZYMES. L53

for some time without injury, according to Taylor's obser-
vations. The presence of even a small amount of water
soon makes the highest temperature that this lipase can
withstand fall far below the boiling-point.

Quantitative studies show7 that the activity of lipase is as
dependent upon external conditions as is the activity of other
enzymes. An increase in the concentration of the lipase in
a reaction mixture is followed by an increase in the velocity
of the cleavage of the fat, but by no means in proportion to
the amount of lipase added.

The amount of fat split in a reaction mixture under the
influence of lipase increases with the' time, but becomes less
in each succeeding unit of time. All the fat is never split,
even when infinite time is allowed, owing to the fact that
the activity of this ferment is reversible.

Lipase is exceedingly sensitive toward acids, losing its
activity, for example, in a very few minutes in a hydrochloric-
acid solution having the concentration of the acid in the
stomach. At the height of digestion the lipase found in the
stomach can therefore have but little or no effect upon the
fats of the food. Lipase acts best in a neutral or slightly
alkaline medium. Its activity is markedly reduced or done
away with entirely through the presence of various neutral
salts.

That the activity of lipase is reversible was demonstrated
in this country by Kastle and Loevenhart,1 and independ-
ently of them by Hanriot2 in France. Kastle and Loeven-
hart were able to show that if lipase is added to ethyl butyrate
this is split into ethyl alcohol and butyric acid. The re-
action is, however, incomplete. If, on the other hand, lipase
is added to a mixture of ethyl alcohol and butyric acid, ethyl
butyrate is synthesized.

This may be illustrated by the following experiment:

'Kastle and Loevenhart: American Chem. Jour., 1900, XXIV,
p. 191.

2 Hanriot: Compt. rend. Soc. biol., 1901, LIU, p. 70.

152 PHYSIOLOGY OF ALIMENTATION.

1000 c.c. of an extract of ground pancreas were mixed with
1900 c.c. of a 1/10 normal butyric-acid solution and 100 c.c.
of 95 percent alcohol. To the mixture was added some
thymol to prevent the development of bacteria, and the
whole was kept for 40 hours at a temperature of 23° to 27° C.
A similar mixture was prepared as a control, only the pan-
creatic extract was boiled before being mixed with the
butyric acid and alcohol. At the conclusion of the experi-
ment 25 c.c. were distilled over from each of the flasks.
Had any ethyl butyrate been synthesized from the butyric
acid and alcohol this distillate ought to contain it. It was
found that the distillate from the first flask, containing the
unboiled pancreatic extract, smelled strongly of ethyl butyrate,
and after being further purified rendered water milky when
poured into it, owing to the formation of the only partially
soluble ethyl butyrate droplets; it formed a soap (sodium
butyrate) upon the addition of NaOH, and yielded butyric
acid when digested with lipase. The distillate from the flask
containing the boiled pancreatic extract smelled of butyric
acid, gave no turbidity when poured into water, and was un-
changed through the addition of lipase. A synthesis of
ethyl butyrate from butyric acid and alcohol under the in-
fluence of a substance contained in the pancreas and de-
stroyed by heating— in other words, the synthesis of an
ester under the influence of lipase — seems proved by this
experiment.

Just as in the analysis of an ester (or fat) the reaction is
incomplete, so, too, is the synthesis. Before all the butyric
acid and alcohol have been built up into ethyl butyrate, the
reaction comes to a standstill (practically speaking). We
are in this case also dealing with a reversible reaction cata-
lyzed by a ferment. The lipase acts just as the maltase did
in the case of maltose and glucose — it only hastens the estab-
lishment of an equilibrium between the fat (ethyl butyrate
in this case), on the one hand, and fatty acid and alcohol, on
the other. Whether lipase will have an analytic or a syn-

ACTION OF THE ENZYMES. 153

thetie action upon any mixture of fat, fatty acid, and alcohol
is dependent solely upon the relative amounts of these sub-
stances present. Speaking broadly, the lipase will analyze
fat whenever this substance is present in excess, while it will
synthesize it if the fatty acid and alcohol are in excess, and
it will do one or the other of these until equilibrium has been
established.

Hanriot worked not with ethyl buytrate but with mono-
butyrin, which under the influence of lipase is split into
glycerine and butyric acid. When, under proper external
conditions, lipase is added to a mixture of glycerine and
butyric acid, monobutyrin is produced, as Hanriot was
able to show by isolation of that compound.

The synthesis of chemically much more complicated esters
than ethyl butyrate can, however, be brought about through
lipase. With the lipase obtained from the castor-bean
Taylor * succeeded in synthesizing triolein from a mixture of .
oleic acid and glycerine. Since this same ferment is un-
able to split triolein and other fats completely, the reaction
coming to a standstill when some 75 to 90 percent of the
original fat has been broken up into glycerine and oleic acid,
the conclusion seems to be justified that the lipase obtained
from this source is also able to catalyze both the analysis and
the synthesis of fats in a way similar to that described in
Kastle and Loevenhart's experiments.

12. Sucrase (invertase, invertin) is a ferment which is I
characterized by its power of splitting the disaccharide, cane=
an p. r fsijernsM into a mivfip-n of two monosaccharides^ The
monosaccharides produced are known as "iuxGLt=£li£^r,"
and consist of a mixture of equal parts of dextrose and hriVU-
lose. The change which cane-sugar undergoes under the
influence of sucrase is expressed by the following formula:

C12H22O11 +HoO = CfiHi206 +CI1il>( V,

Sucrose Water Dextrose Ltevulose

'Taylor: University of California Publications, Pathology, 1904,
I, p. 33.

154 PHYSIOLOGY OF ALIMENTATION.

Sucrase is found widely distributed throughout the vege-
table kingdom. In animal physiology it finds its importance
as a constituent of the intestinal juice. Its presence has also
been claimed in the secretions of the mouth and stomach.
In the former of these sucrase is probably not present as a
constituent of the saliva itself, but is to be looked upon rather
as a contamination due to the excretion of this ferment by
some of the bacteria which are constantly present in the
t buccal cavity. The view that bacteria are the source of the
' sucrase of the stomach is probably also correct. Some of the
authors who have concluded that sucrase is present in the
pure secretion of the stomach, simply because the gastric
juice has the power of inverting cane-sugar, have overlooked

Ithe fact that the hydrochloric acid has this power by itself.
In foot most of the invert-sugar which is found in the stomach
after a meal of cane-sugar is attributable to the action of,
the hydrochloric acidj. Most of the cane-sugar which enters
the alimentary tract seems to remain unaltered, however,
until it comes in contact with the juices of the small intestine.
^ For study sucrase is usually obtained from ypa.st^ a. pnlt^rp
of asper^illns. or sorrm nthw vpo^to^jp r>Qj] The method
of Duclaux, which probably yields the most active prepara-
tions of the enzyme, consists in growing aspergillus upon a
nutrient fluid for several days, and later substituting a solu-
tion of cane-sugar for the nutrient fluid. After growing upon
this for about three more days, the mould gives off its sucrase
to the solution. The whole is then filtered, and the filtrate
vhich represents a solution of sucrase is used for the purposes
iesired. It is also possible to obtain sucrase in a dry but less
active state by the method of Denathe. Yeast, after being
kept under absolute alcohol for a time, is dried, pulverized,
and extracted with water. After filtering, ether is added
to the filtrate and the whole shaken. A gummy mass sepa-
rates, which is dissolved in distilled water, and this solution is
added drop by drop to absolute alcohol. The powdered pre-
cipitate obtained in this way is separated by filtration and

ACTION OF THE ENZYMES. 155

dried. The resulting while powder keeps for a long time,
and when dissolved in water shows great diastatic ac-
tivity.1

The inversion of cane-sugar as catalyzed by sucrase is
markedly influenced by time, concentration of the ferment,
temperature, and other external conditions. In infinite time
a small amount of the ferment brings about as much change
as a larger amount. If the products of the reaction (dextrose
and lsevulose) are not removed, the reaction is incomplete,
and when the catalysis has come to a standstill all three sub-
stances are present in the reaction mixture. It is ordinarily
said that the products of the reaction interfere with the action
of the enzyme — a fact which we have learned before in the
consideration of most of the other ferments. The catalysis
of the cane-sugar under the influence of sucrase, and the
catalysis of the same substance under the influence of acids —
which bring about the same chemical change in the sucrose —
differ in this regard, for no limit is reached when acids are
employed, the inversion being in this case complete.

Only when the concentration of the ferment is high, the
temperature low, and the experiment continued for but a
short time does an almost constant relation exist between
the concentration of the ferment and the amount of invert-
sugar formed. This explains, for example, the results of
O'SuLLivANandToMPSON, who believed that the catalysis of
cane-sugar under the influence of sucrase was governed by
the same laws as the catalysis under the influence of acids.
In every experiment which is continued a sufficient length
of time, the amount of invert-sugar formed in the unit of
time from the sucrose in the presence of sucrase gradually
diminishes. The point at which the reaction comes to a
standstill varies with external conditions of temperature,
concentration of the reaction mixture, etc. But only when

1 See Effront: Die Diastasen. Translated into German l>y BttCH-

eler, Leipzig, l'JUO, I, p. 5U.

156 PHYSIOLOGY OF ALIMENTATION.

the products of the inversion are removed does the catalysis
go to an end.

The optimal temperature for sucrase is given by Kjeldahl
as 52° C. for a preparation obtained from yeast. Effront
states that at 0° C. the activity of sucrase is practically nil,
rises slowly up to 30° C. to increase more rapidly up to 50° C,
after which it falls again. At a temperature of 65° C. the
ferment is rapidly destroyed. External conditions modify
very markedly the points at which the optimal temperature
and the maximal temperature are attained.1 While a dilute
solution of sucrase may be kept at 52° C. for an hour without
losing its fermentative activity, more concentrated solutions
suffer considerably if kept at the same temperature for even
shorter periods of time. At 65° C. a concentrated solution
of sucrase is entirely destroyed within an hour, while a more
dilute solution bears this treatment with only a partial loss
of its activity. Besides these variations in optimal and maxi-
mal temperatures in the same preparation of sucrase under
different external conditions, marked differences are also
found between sucrase preparations obtained from different
sources. The various sucrase preparations differ, for example,
in their optimal and maximal temperatures, in their resistance
to chemical and physical agents, etc. On this ground certain
investigators have tried to establish the existence of varieties
of sucrase. The same can be said of this ferment, however,
which has been said of others, that when obtained from dif-
ferent sources the impurities accompanying the preparations
are not the same. Preparations of sucrase differ, therefore,
not because of specific differences in the sucrase itself, but
because of specific differences in the impurities accompanying
the sucrase. Certain of these act more deleteriously upon the
enzyme than others, and we get in consequence the long line
of differences which authors have claimed exist in the sucrases
themselves.

1 By maximal temperature is meant the temperature at which the
fermentative reaction no longer takes place.

ACTIOS OF THE ENZYMES. 107

It has been shown by Kjeldahl that sucrase acts best in a
slightly acid medium. A greater concentration of the acid,
be it inorganic or organic, acts deleteriously, ns does also an
alkali in any concentration. In fact the activity of sucrase
is markedly influenced by a concentration of alkali, the pres-
ence of which cannot even be recognized by our ordinary
indicators. As the intestinal juice is neutral or if anything
slightly acid, we see that sucrase acts, so far as reaction is
concerned, under favorable conditions in the body.

13. Lactase is a ferment which has the power of acting
upon the disaccharide lactose (milk-sugar) and converting it
into the monosaccharides d-glucose (dextrose) and d-galac-
tose.

C12H22O11 +H2O =CeHi206 +C6H12O6.

Lactose Water Dextrose Galactose

Various yeasts usually serve as a source of the ferment which
has been studied more particularly by Beyerinck,1 Emil
Fischer,2 Armstrong,3 and Weinland.4 Emil Fischer ob-
tained the ferment most readily by making an aqueous ex-
tract of Saccharomyces Kefir and precipitating the ferment
with alcohol. The reversible activity of this enzyme has
been demonstrated by Emil Fischer and Armstrong, who
found that milk-sugar (or at least a disaccharide closely re-
lated to it) appears in a concentrated mixture of d-glucose
and d-galactose under the influence of lactase, when the
whole is kept in a thermostat at 35° C.

The fact that milk-sugar is one of the commonest constitu-
' nts of our food, especially in suckling animals, gives the
occurrence of lactase in certain organs its physiological im-
portance. The exceedingly contradictory statements of dif-

1 Beyerinck: Contrail)!, f. Bacterid., 1889, VI, p. II.

2 Emil Fischer: Berichte d. deut. chem. Gesellsch., L894, XXVII,
3481.

3 Emil, Fischer and Armstrong: Berichte d. deut. chem. Gesellsch.
1902, XXXV, |>. 3144.

4 Weinland: Zeitschr. f. Biol., 1899, XXXVIII, p. 606.

158 PHYSIOLOGY OF ALIMENTATION.

ferent investigators regarding the presence or absence of
lactase in different organs and secretions of the alimentary
tract have been harmonized by the careful experiments of
Weinland. There seems to be no question but that lactase
is present in the secretions and mucous membrane of the small
intestine of all suckling animals and in certain adult animals,
provided they are fed milk-sugar or a food containing it.
The same holds true of the pancreas. Sucklings secrete
lactase in their pancreatic juice, and the gland contains
the enzyme. Adult animals come to have lactase present in
their pancreas if they are fed milk-sugar.1

14. Arginase. — Under this heading Kossel and Dakin2
have described a ferment which has the interesting property
of acting upon arginin and splitting this into the chemically
much simpler ornithin and urea. The ferment is widely
distributed throughout the body, though it is present in
different amounts in the various organs. The liver probably
contains the largest amount, while next in order come the
kidneys, spleen, and intestinal mucous membrane.

Arginase can be readily obtained by extracting any of the
organs named with water and dilute acetic acid, but, as with
other ferments, only a small portion of the ferment actually
present within the tissues can be gotten out. Absolutely
pure arginase has not as yet been prepared, but advantage
can be taken of the fact that it is readily precipitated by
ammonium sulphate, and alcohol and ether to free it from
many of the impurities which accompany the ordinary acetic-
acid extract.

Some idea of the readiness with which arginase acts upon
arginin can be obtained from the following experiments , in
which are indicated the amounts of this substance which
may be split in ten minutes by an extract made from 25
gms. of liver substance. In one experiment 2.7 gms. of the

1 See Chapter XII.. Part 7.

2 Kossel and Dakin: Zeitschrift fur physiol. Chemie, 1904, XLI, p.
341, and XLII, p. 183.

ACTION OF THE ENZYMES. I 5'.)

original 3.2 gms. of arginin that were Added to such an
extract, were split, 2.0 gins, of ornithin and 1.1 gms. of urea
being recovered from the reaction mixture. In another
experiment 3.3 gms. of arginin of the original 3.6 gms.
added were split, 2.7 gms. ornithin and 1.2 gms. urea being
recovered.

These experiments furnish an interesting example of the
apparent ease with which chemical changes are brought
about in a living organism, which in vitro cannot often be
accomplished without resort to what may be termed coarse
chemical procedures. The ease with which arginase splits
arginin into ornithin and urea stands in sharp contrast to
the difficulty with which this same chemical change is brought
about under the influence of boiling mineral acids.

The experiments of Kossel and Dakin give us an insight
into the means by which urea is produced in the liver and
various other organs of the body. Whether the urea which
was found by Claude Bernard and others in the secretions
of the intestine is dependent upon the presence of this en-
zyme in the wall of the gut, or whether we have in addition
a true excretion of this substance by the intestinal canal,
cannot be settled until further experiments have been made.1

See Chapter XVIII. Part 1.

CHAPTER IX.

THE BACTERIA OF THE ALIMENTARY TRACT.

A discussion of the bacteria of the alimentary tract fol-
lows very naturally upon a discussion of the enzymes elab-
orated here, for the various bacteria contain enzymes in
their bodies and secrete them. Some of these bacterial en-
zymes are not unlike those which are secreted by the glands
of the alimentary tract. By virtue of these, the bacteria may
therefore augment, in a limited way, the activities of the
alimentary secretions. In large part, however, the bac-
terial ferments are able to bring about changes in the ali-
mentary contents which differ totally from those brought
about by the secretions of the alimentary tract proper. The
substances formed in this way are usually harmless in char-
acter, though at times, through excessive production or
through the formation of specific poisonous substances, they
assume even a pathological importance.

The subject of the bacteria of the alimentary tract, to-
gether with a discussion of their physiological and patho-
logical role, has given rise to a literature which is simply
enormous. Nor do the conclusions reached by the various
authors at all harmonize — a fact not strange when the com-
plexity of the problem is recognized. For under normal
and abnormal conditions practically every form of bacterium
enters the intestinal tract, and when it is remembered that
usually more than one kind of micro-organism is present at
the same time, that the medium upon which they grow (food,
etc.) is subject to the greatest variation, and that the agencies

160

THE BACTERIA OF THE ALIMENTARY TRACT. 101

active in inhibiting their growth and reproduction arc prac-
tically not at all understood, it is not strange that opinions
differ.

1. That bacteria exist throughout the alimentary tract is
no longer doubted by any one. At what time do these bac-
teria appear? The majority of investigators are agreed that
under normal circumstances the alimentary traot of new-born
animals is sterile. This condition of affairs does not last
long, however, for, as shown by the observations of Popoff,
Schild, and Escherich, the faeces of young children may con-
tain several kinds of bacteria as early as ten hours after birth,
and only rarely are they absent at the end of twenty-four.
Bordano found even the colon bacillus thirteen hours after
birth. These bacteria enter the intestinal tract through
air, food, and bath-water by way of the mouth and rectum.1

2. In order to show the enormous number of bacteria
which inhabit the intestinal tract, the figures of Sucksdorff2
may be cited, who found in one milligram of normal human
faecal matter an average of 381,000 micro-organisms. Yet
the figures vary considerably, even within twenty-four hours,
between the extremes of 2,300,000 and 25,000 per milligram.
The variation in the number is, according to Sucksdorff, de-
termined chiefly by the kind of food, and but little by the total
amount of fseces or the amount of water contained in them.
When only sterile food is consumed, the average number of
bacteria per milligram is markedly reduced. Brotzu3 has
observed that this is true for the dog also when fed onty
sterile food. From the total amount of faeces cast off and the
number of micro-organisms contained in each milligram, the

1 See, for example, J. H. F. Kohlbuugge: Centralbl. f. Bakt., 1001,
XXX, lte Abth., p. 17; Gerhardt: Ergebnisse der Physiologic, L904,

111 lte Abth., p. 107, where extensive references to the literature may
be found.

2 Sucksdorff: Arch. f. Ilyg., 1886.

3 Quoted from Kohlbuuggi:: Centralbl. f. Bakt., 1901, XXX, lte
Abth., p. 13.

162 PHYSIOLOGY OF ALIMENTATION.

total number of bacteria voided in twenty-four hours can be
calculated. For this figure Gilbert and Dominici give as an
average 12,000 to 15,000 millions; Sucksdorff 55,000 millions;
Klein,1 who probably used the best technique of the three,
8,800,000 millions.

3. The weight of the bacteria excreted in twenty-four hours
has been calculated by Kleyn,2 who estimates that 1.13 per-
cent of the dry faeces is made up of micro-organisms and that
about 293 milligrams are cast off in twenty-four hours.

4. As to the kinds of bacteria inhabiting the alimentary
tract, the following may be said. We must distinguish first
of all between those bacteria which are almost constantly
present in the digestive tube and those which are present
only under certain circumstances. Under the latter head-
ing we can say that practically every known form of micro-
organism has been found in some portion of the intestinal
tract at some time. A large number of saprophytic bacteria
are always found in the mouth. After inhaling the air of
rooms in which infectious diseases have been housed, the
bacteria characteristic of that disease have been recovered
from the mucous membranes of the mouth, throat, and nose
of those who have lived in these rooms. But even from
the noses and mouths of persons following the ordinary rou-
tine of life have virulent pathogenic bacteria been culti-
vated. This has been done repeatedly for the ordinary pus
organisms, and Noble W. Jones has shown that virulent
tubercle bacilli are not uncommon inhabitants of these regions.
For the most part these, even pathogenic, bacteria are of
little or no importance. When, however, the health of the
individual as a whole, or the resistance, as we are pleased
to call it, of the tissues inhabited by these micro-organisms
is reduced through any cause whatsoever, they are able to
produce their characteristic pathological effects.

The oesophagus harbors practically the same bacteria that

1 Klein: Centralbl. f. Bakt., 1899, XXV, p. 278.

2 Kleyn: Cited from Kohlbrtjgge, 1. c.

'nil- IIACTKUIA OF Till: M./MK.XTARY TRACT. 163

are Found in the mouth, as the inhabitants of this region are
simply carried through this tube by the swallowed saliva and
food. In the stomach (lie number of bacteria is greatly re-
duced, :i large number of them, as will be shown later, being
destroyed by (he gastric juice. Yet by no means all of them
arc destroyed, the spore-bearing varieties being especially
successful in withstanding (he action of (he gastric juice.
Yet the oilier varieties — such as the ordinary pus bacteria —
can also traverse the stomach without losing their pathogenic
properties. It is certain that some at least of the majority
of 1 he bacteria found in the mouth can pass the stomach and
be carried through the entire intestine uninjured, for Miller1
was able to isolate from the stools 12 of 25 different varieties
which he had recognized in the mouth.

Only few varieties of bacteria are found throughout the
small intestine. As the caecum is approached, however,
their number increases somewhat, to approach a maximum
in the ascending colon. From here to the rectum the sep-
arate varieties change but little.

Though the last experiments have not yet been made in
this field it seems fairly certain that most of the strict anae-
robes are never found anywhere in the alimentary tract after
the stomach is passed. Of the varieties of bacteria which are
found we will not mention those which are recognized as the
cause of certain primary diseases, nor those which may be
found, but only those which, generally speaking, arc almost
always present. Of these the following are the most im-
portant.

As a constant inhabitant of (he upper portions of the small
intestine of sucklings Escherich has found the Bacterium
lactis acrogenes, which is able to exist here because of its power
of splitting up the milk-sugar of the food, from which it obtains
its necessary supply of oxygen. Corresponding with the
ever-diminishing amount of milk-sugar in (he intestine from

1 Miller: Deutsche med. VVochenschr., L885, p. 843,

164 PHYSIOLOGY OF ALIMENTATION.

above downwards it is found that the number of bacteria
of this variety also decreases. As another constant inhabi-
tant of the alimentary tract beyond the stomach we have the
Bacillus coli communis, which according to Escherich first
appears in small numbers high up in the small intestine.
From here the number of bacteria of this variety increases
progressively from above downwards. Kohlbrugge ques-
tions the presence of the Bacillus coli communis in any por-
tion of the small intestine except the region near the ileocsecal
valve. The csecum is considered by the last-named author
as the distributing depot of the colon bacillus, from which it
is supposed to be carried outward toward the rectum. By
the term colon bacillus are here understood all the different
varieties of this micro-organism which have been described.

The two above-mentioned bacteria were for a long time
held to be the only constant inhabitants of the intestinal canal.
Since Escherich's early work we have become acquainted,
however, with a number of others which seem to be constant
inhabitants of the large bowel, and the cause here of certain
of the putrefactive changes which occur in this region of the
intestinal tract and not above it. Under this heading belong
the Bacillus putrificus, certain members of the Proteus group,
and bacteria very similar to the Bacillus subtilis. The first
of these is an anaerobe and the cause of the bacterial decom-
position of the proteins of the food. The products of this
decomposition give the faeces their odor. The absence, as
a rule, of the Bacillus putrificus from the intestine above the
ileocsecal valve in the adult explains why the contents of
the small intestine are without odor. The faeces of children
are also free from odor because their intestinal tracts nowhere
harbor this bacillus. Mention must also be made of the Ba-
cillus acidophilus, an acid-producing organism which, like the
colon bacillus, may at times be pathogenic, at times harmless.1

1 Escherich, Kohlbrugge, etc.: Centralbl. f. Bakt., etc., 1901,
XXX, lteAbth.,p,73.

THE BACTERIA OE THE ALIMENTARY TRACT. L65

As more or less constant inhabitants of various portions of
the intestinal tract have also been described certain spirilli
and blastomyces (yeasts) as also moulds and streptobacilli.
The majority of these are harmless saprophytes. It must
also be mentioned in this connection that it is probable that
the faeces contain bacteria which it has not as yet been pos-
sible to cultivate on artificial media.

5. The following may be said regarding the distribution
of the bacteria in the alimentary tract. The mouth has an
exceedingly plentiful bacterial flora which through the
agency of the food and swallowed saliva is carried down
the oesophagus. In the stomach the bacteria become greatly
reduced in number. This is dependent upon the fact that
the secretions of the gastric mucosa destroy or at least
inhibit the growth of micro-organisms in this organ. Which
constituent of the gastric juice it is that brings about this
sterilization in the stomach is not entirely decided, but it
seems to be the hydrochloric acid. The pepsin by itself
has no apparent action upon the bacteria and simple hydro-
chloric-acid solutions of the concentration found in the
stomach are sufficient to bring about the same degree of
bacterial destruction as is brought about by the gastric juice.

The bactericidal effect of the gastric juice is of no mean
( linical importance, for, as has been shown by Oppler, Sei-
fkrt, M ester, and others, gastric and intestinal fermentation
is much greater in cases of anacidity of the stomach than
under normal circumstances. Oppler believes that many
chronic diarrhoeas are primarily dependent upon a lack of
acid in the stomach, and Mester has found that while in-
testinal putrefaction is not increased when putrid meat
is fed to healthy dogs, this is the case when anacidity is
present. To the decreased amount or total lack of hydro-
chloric acid is also attributable the presence of butyric and
other fatty acids in the stomach contents of patients suffer-
ing from gastric carcinoma and other diseases of t lie stomach.
These acids are produced in part through the deeomposi-

166 PHYSIOLOGY OF ALIMENTATION.

tion of the fatty constituents of the food by certain bacteria
which are killed when the secretions from the gastric mucous
membrane are normal, in part through the action of the
lipase normally present in the gastric secretion, which in
the absence of hydrochloric acid can exhibit its character-
istic activity.

Throughout the duodenum, jejunum, and ileum bacteria
are exceedingly scarce, dependent also it seems upon a
deleterious action of the secretions of these portions of the
alimentary tract upon the bacteria. It is entirely probable
that the scant bacterial development found in these locali-
ties is determined chiefly by the fact that the alimentary
contents are neutral or faintly acid in reaction. The pres-
ence of even traces of free acids inhibits the growth of most
bacteria very markedly. It must be remembered also that
the food passes through the small intestine fairly rapidly,
so that little time is allowed for bacterial growth.

The pancreatic juice does not seem to have any bac-
tericidal action. Duclaux found bacteria as constant inhab-
itants of the pancreatic duct, where they are bathed in the
secretions from the gland. They also develop readily on
macerated pancreas. It is of interest after what has been
said above that the pancreatic juice is alkaline in reaction.

Nor has the bile any great antiseptic, action, for accord-
ing to Talma even but slightly virulent colon bacilli can
produce a severe inflammation of the liver when injected
into the gall-bladder. Whether the pancreatic and biliary
secretions together, or these in conjunction with the intestinal
juice, have a bactericidal action is not yet determined.

In the large intestine, beginning with the caecum, the
number of bacteria increases enormously to reach, by the
time the rectum is reached, the gigantic proportions which
have been discussed above. The cause of the prolific develop-
ment of micro-organisms in the large intestine is by no means
clear. The fact that the intestinal contents assume an
alkaline reaction after the ileocecal valve is passed no

THE BACTERIA OF THE ALIMENTARY TRACT. 167

doubt plays an important rule Again, the time which the

food spends in this part of (lie intestinal canal is far greater
than that in any <>f the preceding portions, so that the
time allowed for the multiplication of the bacteria is cor-
respondingly greater. We must, moreover, remember the
antiperistaltic movements of the transverse and ascending
colon as a potent factor in carrying the bacteria from the
descending arm of the large bowel into the transverse and
ascending portions of the colon. Bacteria are constantly
entering the alimentary tract by way of the rectum. Until,
however, we are better acquainted with the physiology of
the development and growth of bacteria, we can expect
to make but little progress in this as well as in other branches
of bacteriology. Systematic studies of the influence of
external conditions upon bacteria, such, for example, as
William B. Wherry1 has recently begun on cholera and
which promise so much in the advance of our knowledge of
mycotic diseases, are still very rare.

The question naturally suggests itself as to how the bac-
teria get from the mouth into the large bowel if the stomach
through which all the food passes has such well-marked
bactericidal action. We answer this question at present
by saying that the bacteria are either not all killed, that
they pass through in the form of spores, or finally, that
they are not affected by the gastric juice because they are
enclosed in particles of food. But even the practically
empty intestinal tract of starvation is not entirely free
from bacteria, from which the conclusion has been drawn
that the intestine has a flora of its own. Great care must,
however, be exercised in accepting this view, as it has not
yet been proved that the various bacteria found in star-
vation are not such as are capable of living on the secre-
tions of the intestinal mucosa alone. As these secretions
are different in different portions of the intestine it is not

'Wherry: Journal ol Infectious Diseases, 1905, II, p. .'>U'.>.

168 PHYSIOLOGY OF ALIMENTATION.

strange that larger numbers of micro-organisms should also
live in some portions of the gut than in others. The exist-
ence of a greater variety of bacteria in certain portions of
the alimentary tract would also increase the chances for a
symbiotic development here. At any rate in the absence
of systematic observations on the effect of external con-
ditions upon bacteria we must be exceedingly careful in
accepting any explanation of their distribution throughout
the alimentary tract which is based upon purely vitalistic
conceptions.

6. Much has been and more will be written concerning
the influence of the ordinary bacterial inhabitants upon the
general health of the host. The majority of investigators
seem agreed that under ordinary circumstances the bac-
teria of the alimentary tract (even the pathogenic which
are found here) do not penetrate the intestinal mucosa.
Under various as yet entirely unknown conditions, however,
these micro-organisms may pass readily through the wall
of the gut. This is very generally the case shortly after
death, and during life is perhaps the cause of certain local
or general infections which start from the intestinal tract.
Why the intestine should under certain circumstances lose
its power of holding back these micro-organisms is not yet
explained. It is not improbable, however, that the taking
up of bacteria by the cells of the intestinal wall is deter-
mined at least in part by the same circumstances which
determine the taking up of bacteria by the leucocytes,
namely, alterations in surface tension. It would not be
strange to find that all those conditions which determine
the entrance of bacteria into the intestinal mucosa are such
as alter the surface tension of the cells composing it.

Even if under ordinary circumstances bacteria do not pass
through the walls of the alimentary tract the same cannot
be said of their products. Many of these are readily diffusible
and so are absorbed. These products of bacterial activity
are at times harmless, at other times intensely poisonous.

THE BACTERIA OF THE ALIMENTARY TRACT. 1G9

A discussion of the prod mix of bacterial activity in the
alimentary tract is therefore next in order. Without enter-
ing too deeply into the chemical changes which the indi-
vidual varieties of bacteria are capable of producing in the
intestinal contents, the alimentary flora as a whole may
be looked upon as able to bring about the following well-
established decompositions. The amount of such decom-
positions is, of course, again dependent upon a large num-
ber of external conditions, of which we need mention by
way of illustration only the character and amount of food
consumed, the length of time that such food remains in
the intestinal tract, the reaction of the intestinal contents
as determined by physiological or pathological variations
in the secretions poured out upon the food, etc.

The bacteria of the alimentary tract contain in their
bodies or secrete, first of all, a number of enzymes which
are not unlike those which are normally poured out upon
the food in its passage from mouth to anus. We need
mention here only amylase, sucrase, and lactase, which
like the ferments normally poured out upon the food con-
vert starch into maltose, cane-sugar into dextrose and
laevulose, and milk-sugar into dextrose and galactose. Pro-
teolytic enzymes probably identical with acid- and alkali-
proteinase (pepsin and trypsin) are also found in the ali-
mentary bacteria. By virtue of these they not only split
proteins into albumoses and peptones but even into the
ultimate digestion products (mono- and diamino-acids)
with which we have already become acquainted in the dis-
cussion of the proteolytic enzymes found in the alimentary
secretions proper. Lipase is also found in certain of the
intestinal bacteria, so that the presence of fatty acid in
the intestinal contents must be attributed at least in part
to the activities of these micro-organisms. Atone time the
presence of fatty acids in the stomach in cases of carci-
noma and other diseases which may be associated with a
decreased amount or entire lack of hydrochloric acid was

170 PHYSIOLOGY OF ALIMENTATION.

attributed solely to the activities of lipase-containing bac-
teria found here. Since we have become acquainted with
the presence of lipase in the normal secretions of this viscus,
this idea must be modified, and the two sources of li-
pase be taken into consideration. Mention must finally
be made of the cytase which certain of the intestinal bac-
teria contain. This ferment has the power of acting upon
cellulose and converting it into dextrin and glucose.

From what has been said, therefore, it can readily be
seen that certain of the bacteria of the intestinal tract may
even be of service to the animal which harbors them, for
they produce changes in the alimentary contents not unlike
those brought about by the normal secretions, and in the
last example cited above, they may even render an other-
wise useless constituent of our food (the cellulose of the
vegetable cells) useful to the animal organism by convert-
ing it into substances which can be taken up by the body.
While these cytase-containing bacteria probably play only
an insignificant role in the digestive processes of the car-
nivora, the herbivora no doubt are dependent upon these
bacteria in no mean way, for even if the amounts of dex-
trin and glucose formed in the hours during which the bac-
teria are active are not very large, the dissolution of the
cellulose walls of the vegetable cells liberates their more
readily digestible contents and so puts these into a posi-
tion to be absorbed.

So far as the amount of the just-described forms of diges-
tion of which the various bacteria are capable is concerned,
it is no doubt correct to say that as compared with the
activities of the normal secretions of the alimentary tract
this is, under ordinary circumstances, comparatively little.

We come now to the bacterial decompositions in the ali-
mentary tract which are apparently of no service to the host
and which are at times of a distinctly injurious character.
It is these that have excited the greatest amount of medical
discussion and have led to the volumes of literature on in-

THE HACTERJA OF THE ALIMENTARY TRACT 171

testinal putrefaction, its qualitative and quantitative det< r-
mination, its physiological and pathological importance, and
the means of combating it. Of the nature of these decompo-
sitions we know as yet but. little. That they are enzymatic
in character is proven by numerous experiments and is gen-
erally conceded, but of the nature of the individual enzymes
which are active we are almost entirely ignorant, as also of
the finer chemistry of the changes which occur in the alimen-
tary contents in their transformation into the substances
which we recognize as the products of bacterial activity.

When the alimentary contents are analyzed chemically it
is found that a fairly distinct division can be made between
the nature of the substances found above, and those dis-
covered below the ileocsecal valve. The bacterial decom-
position products found in the stomach may be dismissed
with the statement that under normal conditions none
are found. This is dependent upon a number of facts:
first of all the high acidity of the gastric juice which lies
far above the limits inside of which most fermentative
changes can take place, and secondly, the short time (at
most a few hours) that the food remains in this viscus. What-
ever bacterial decompositions are possible in the stomach
can, therefore, never reach a high grade in the limited time
allowed for such changes under normal circumstances. The
physiological importance of these two circumstances mani-
fests itself most clearly when through experiment or disease
they are missing. Every day clinical observation suffices to
show how the stomach contents of a patient whose gastric
juice contains too little acid, or whose stomach does not
empty itself except after long intervals, are teeming with
bacteria and the products of I heir enzymatic activities.
These products differ and fall into the group of those derived
from the fats, carbohydrates, or proteins of the ingested food
according to the conditions found in the stomach as deter-
mined by the changes in the viscus itself, the food, and the
character of the bacteri; i n sent.

172 PHYSIOLOGY OF ALIMENTATION.

Our knowledge of the bacterial products present in the
small intestine of the human being has been derived from
analyses of intestinal contents obtained from patients suf-
fering from intestinal fistulse. The observers who have
worked in this field all agree that the contents of the small
intestine are acid in reaction, determined, however, not by
free hydrochloric acid, but by fatty acids resulting in the
main from the activity of the lipase produced by the pancreas
and the intestinal wall upon the fats of the food, but also in
part due to the action of lipase-containing bacteria. No in-
considerable amount of acid seems to be derived from the
carbohydrates through the action upon them of the bacteria
found in the small intestine. Among the acids formed in
this way in small amounts under normal conditions, and in
often enormous amounts in pathological states may be men-
tioned acetic, different kinds of lactic, succinic, butyric, and
formic acids. The excessive formation of these acids is at
once brought about when from any cause — such as insuf-
ficiency of the secretions of the alimentary tract, or insuf-
ficiency of the proper ferments in these secretions, or enjoyment
of excessive amounts of carbohydrates — these are not digested
and absorbed in the proper way and so become the prey of
the bacteria always present here. The formation of small
amounts of these organic acids need not be followed by se-
rious consequences. Small amounts may be absorbed, oxi-
dized in the tissues, and no evil consequences result. Others
undergo further change in the alimentary tract and are con-
verted into water, carbon dioxide, marsh-gas, and hydrogen.
The organic acids produced bring about, even in small amounts,
an increased peristalsis and an increased secretion of water
into the intestine, so that if the condition is at all marked,
frequent liquid stools, acid in reaction and ill-smelling, result.
The presence -of gases in the intestines also induces peristalsis.
It is clear that a slight alimentary fermentation need not
be an evil thing. Unquestionably the beneficent effects of
the addition of vegetables to an ordinary mixed diet in bring-

THE BACTERIA OP THE ALIMENTARY TRACT. 173

ing about a more regular discharge of the faeces is due quite
as much to the fact that the celluloses, starches, and sugars
contained in the vegetables are not readily attacked (because
of their structure) by the alimentary enzymes and so furnish
a culture medium for the intestinal flora with the product inn
of the above-mentioned acids and gases as to any "mechani-
cal " stimulation which a coarse food is supposed to exert.

It will not seem surprising that acute alimentary fer-
mentations (with diarrhoea and the general symptoms of
intoxication) are much more common after the enjoyment
of excessive amounts of disaccharides (candy, milk-sugar)
than after the use of equally large amounts of starch. Not
only does the absorption of the sugar formed from starch
ordinarily keep pace with its production, but the starches
themselves do not furnish as favorable a culture medium
for the bacteria as do cane-sugar and milk-sugar for example.
These two are not only absorbed comparatively slowly, but
they are readily attacked by bacteria.

Products of protein decomposition such as are generally
looked upon as characteristic of the fermentative activities
of bacteria are found in the small intestine either not at all
or only in small quantities.

With the passage of the alimentary contents through the
ileocecal valve a complete change occurs in the type of
bacterial decomposition found. Instead of the products
of the decomposition of carbohydrates we find now the
products of protein decomposition. This change is deter-
mined by a number of conditions; which is primary and
which is secondary cannot be easily discovered. As the
alimentary contents pass along the small intestine they
become progressively poorer in carbohydrates, so lh.it by
the time the ileocecal valve is reached little or none arc
left to be absorbed. The reaction of the alimentary con-
tents also changes. While above the ileoca?cal valve the
intestinal contents are acid, they are alkaline below it.
The character of the bacterial (i< ra as already outlined above

174 PHYSIOLOGY OF ALIMENTATION.

also changes as we pass through the ileocaecal valve, but
here again it is difficult to decide whether the intestinal
contents determine the character of the flora or vice versa.
The fact remains, however, that while in the small intestine
we deal chiefly with the products of carbohydrate decom-
position we have to do in the large bowel chiefly with the
products of protein decomposition. By virtue of the or-
dinary proteolytic enzymes contained in the bacteria the
undigested proteins suffer a successive cleavage into pro-
teoses, peptones, and finally amino-acids. The decompo-
sition does not cease here but continues in two directions.
First of all the amino group may be split off so that simple
organic acids are left behind. Acetic acid is in consequence
formed from glycocoll, propionic acid from alanin and
valerianic acid from amino-valerianic acid. Succinic acid,
phenylpropionic acid, oxyphenylpropionic acid, and skatol-
acetic acid may also be found. Secondly, carbon dioxide
may be split off from the amino-acids with the formation of
such substances as cadaverin and putrescin. Through fur-
ther oxidation we obtain phenol, indol, and skatol.1 These
in combination with sulphuric acid are excreted in the urine.
Their quantitative estimation in the urine has in conse-
quence been utilized as a test of the amount of putrefac-
tion going on in the alimentary tract.

To the volatile fatty acids and aromatic compounds and to
certain of the gases formed in the action of the bacteria upon
the alimentary contents is due the odor of the faeces and
flatus.

From what has been said in the preceding paragraphs it
might be concluded that the bacteria of the alimentary canal
are either always harmful or at the best of no use to the
host. This is, however, not the case. It has been shown
through the experiments of Nuttall and Thierfeldbr2 that

1 Abderhalden • Physiol. Chemie, Berlin, 1906, p. 1S4.

2 Nuttall andTHiERFELDER: Zeitschr. f. Physiol. Chemie, 1895, XXI
p. 109; ibid., 1896, XXII, p. 62.

THE BACTERIA OF THE ALIMENTARY TRACT. 175

they may even serve a good purpose, for young guinea-
pigs removed from the uterus by Cacsarean section and
kept in sterile vessels, given sterile air to breathe and sterile
food to eat do not thrive as do animals from the same
litter, born under the same circumstances but raised in
ordinary air and on non-sterilized food. It was found that
the latter were uniformly better nourished, heavier, and
lived longer than the former. Schottelius1 has made simi-
lar experiments on chicks and has found that when kept
under absolutely sterile conditions these fowls in twelve
days increase only 25 percent in weight instead of 140 per-
cent, as do the control animals.

1 Cited from Kohlbrugge: Centralbl. f. Bakt., 1901, XXX, lte
Abth., p. 26.

CHAPTER X.
THE REGULATION OF SALIVARY SECRETION.

i. Salivary Fistulae. — The salivary glands have since the
earliest days of experimental physiology served as objects
of investigation, partly through the fact that changes in
the character of their secretions from time to time are readily
apparent and partly because their superficial situation ren-
ders them easily accessible to study.

In order to determine the quantitative or qualitative
changes in the saliva as it is poured out by the three pairs
of parotid, submaxillary, and sublingual glands it is necessary
to collect the saliva as it issues from the ducts. It is pos-
sible to accomplish this in man and various animals by
inserting fine catheters into the ducts of these glands and
allowing the saliva to drip into small glass tubes. Some-
times nature creates salivary fistulae which open externally,
as when salivary calculi ulcerate through the cheek or injuries
of various kinds to a salivary gland or its excretory duct
cause the saliva to flow out upon the skin. The study of
such cases has yielded many valuable physiological data.

The older investigators, in their animal experiments, used
to lay bare the different salivary glands, catheterize the ducts
and collect the saliva which poured out of them. Today, how-
ever, when we have learned how much narcotics and various
operative procedures interfere with the normal function of an
organ we try to employ experimental procedures which do
away with such disturbing influences. In a large number of
experiments it is possible therefore to work on animals in

176

THE REGULATION OF SALIVARY SECRETION. 177

which through previous operation the salivary ducts have
been turned outward in such a way that they pour their
secretions upon the skin where they may be collected and
studied. Not only do such measures bring with them a
great saving of animals, but they constitute the only means
by which we can obtain a true conception of the normal
activity of the gland. How revolutionary are the results
obtained by such experimental means which to all intents
and purposes leave the laboratory animals uninjured, not
only in the case of the salivary glands but all the digestive
glands, will be readily apparent from the pages that follow.
We will describe first of all Glinnski and Pawlow's1
method of making a permanent salivary fistula. A dog is ordi-
narily used. If the parotid saliva is to be collected a small
sound is intioduced into Stenson's duct and under chloroform
anaesthesia a circular incision is made through the mucous
membrane around the orifice of the duct. The duct is care-
fully dissected free from its surrounding tissues and a hole is
punched through the cheek by means of a sharp knife. The
duct is drawn through this hole and the collar of mucous
membrane is sewed into the edges of the hole. After healing
is complete the parotid discharges its secretion upon the
cheek. For a study of the secretions of the submaxillary and
sublingual glands a similar procedure is followed, but since
it is not an easy matter to separate the ducts of 'Wharton
and of Bartholin the two are usually together sewed into the
edges of the external wound. After everything is healed the
secretions from the two glands can be separated by a sec-
ondary operation in which the ducts are ligatured and opened
on the side nearest the gland. In order to collect the saliva
which flows from the glands small flanged glass funnels are
pasted over the openings by means of a laboratory paste, and
from the points of these funnels small graduated tubes are
suspended. A dog which has had one or two glands operated

'Glinnski and Pawlow: Ergebnisse Ucr Physiologie, 1902, 1, lte
Abth., p. 252.

178 PHYSIOLOGY OF ALIMENTATION.

upon in the way indicated suffers absolutely no inconve-
nience, if only care be taken to have the food fed the animal,
when not being used for experimental purposes, sufficiently
moist.

2. The Relation of the Nerves to the Salivary Secretions.
— Each of the three sets of salivary glands is supplied by two
sets of nerves, the one being of cranial origin, the other of
sympathetic. The submaxillary and sublingual glands are
supplied by a branch of the facial nerve — the chorda tympani.
The parotid is supplied by the auriculo -temporal branch of the
trifacial nerve. The sympathetic fibres are derived in the
main from the second, third, and fourth thoracic nerves,
which, after passing into the sympathetic chain, ascend to
the superior cervical ganglion, from which nerve fibres, chiefly
of the non-medullated variety, are given off that, after follow-
ing the external carotid artery, are finally distributed to the
various salivary glands. Let us see now what the effect of
division and electrical stimulation of these various nerves is.
In spite of the many contradictory statements found in the
original papers of different investigators, these all seem to
agree on the following points.

If a glass catheter is introduced into the duct of a salivary
gland, no or only very little secretion flows from it under
ordinary circumstances. If now the cranial nerve supplying
the gland is laid bare (for example, the chorda tympani nerve
to the submaxillary gland of a dog) and divided with a snip
of the scissors, no change occurs. Let, however, the peripheral
end of the divided nerve be stimulated electrically, mechani-
cally, or chemically, and the saliva is seen to move along the
catheter with increased rapidity. Soon a drop falls from its
end, and this is followed by another and another in rapid
succession. By far the most effective form of stimulation is
that with repeated induction shocks. A very weak current
will bring about such an increased flow of saliva, but within
certain limits the stronger the current the greater the flow
of saliva. Since the stronger currents injure the nerve, the

THE REGULATION OF SALIVARY SECRETION. 179

length of time during which the ll<>\v of saliva can be kept
up under these circumstances is appreciably less than when a
weaker current is used. In a properly arranged experiment
with a moderate currenl a flow of saliva may be maintained
an hour or more.

The submaxillary of the dog may secrete in five minutes
an amount of saliva equal to its own weight, and by alter-
nately .stimulating and resting the gland 250 c.c. may be
obtained in 1() to 12 hours. Toward the end of this time
the rate of flow is less than at the beginning of the experi-
ment.1

Some difference exists in the amount and in the character
of the saliva as obtained from the different glands in different
animals. In the dog stimulation of the auriculo-temporal
nerve supplying the parotid by methods similar to those just
described yields from one-half to two-thirds the amount of
saliva obtained from the submaxillary gland. This agrees
with Claude Bernard's finding that when saliva is obtained
refiexly from the dog the submaxillary gland furnishes twice
as much as the parotid and ten times as much as the sub-
lingual gland.

While the composition of the saliva as obtained from the
different glands when their cranial nerves are stimulated is
not the same (the submaxillary saliva, for example, always
contains more organic matter than either the sublingual or
parotid, and the sublingual more salts than either of the other
two), still it is in all cases clear, thin, and watery, and contains
only from 1 to 2 percent of solid matter.

Exposure, section, and stimulation of the sympathetic
fibres going to one of the salivary glands is followed by quite
a different effect. In this case also a flow of saliva is ob-
tained, only much less than when the corresponding cranial
nerve is stimulated, and the; saliva has entirely different
characteristics. While histological study may show that a

1 Langley: Schaefcr's Text-book of Physiology, 1900, Vol. I, p. 493.

180 PHYSIOLOGY OF ALIMENTATION.

secretion of saliva has occurred in a gland shortly after stimu-
lation, as evidenced by the presence of saliva in the smaller
ducts of the gland, external evidence, that is a movement of
saliva in the glass catheter inserted into the duct of Wharton,
Stenson, or Bartholin, is not so readily obtained. Such a
movement is discoverable only after stimulation has been
continued for some time and not witkin a few seconds, as
when the cranial nerves are stimulated. Langley has calcu-
lated that at the best only 1/30 to 1/60 of the quantity of
saliva which would be obtained from the submaxillary gland
were the chorda tympani stimulated is obtained when the
sympathetic fibres of the same gland are stimulated.

In contrast to the clear watery saliva obtained through
stimulation of the cranial fibres, that obtained when the
sympathetic fibres of one of the salivary glands is stimu-
lated is turbid, thick, and ropy. While in such sympa-
thetic saliva great variations in chemical composition are
also found in different animals, it can be said in general
that it is much richer in organic and inorganic material
than is cranial saliva, containing as it does on an average
of from 3 to 4 percent solids.

Various attempts have been made to explain these differ-
ences in the chemical composition of the various salivas
and in the quantities secreted. The nerves have been
charged with a multiplicity of functions, but none of these
explanations can as yet be regarded as satisfactory.

Stimulation of the nerves supplying a salivary gland is
accompanied by a series of accessory phenomena which
deserve notice. When induction shocks are applied to the
chorda tympani nerve, for example, not only does the rate
of salivary secretion increase, but the gland swells, becomes
redder in color, and the efferent veins pulsate with arterial
blood. The chorda tympani, in other words, carries vaso-
motor nerves to the gland. It was once thought that the
increased secretion of saliva was due to this increased flow
of blood through the gland, but this can no longer be held.

THE REGULATION OF SALIVARY SECRETION. 181

It has been found that for a short time at least, a secretion
of saliva can be obtained even from the head of a decapi-
tated animal, in other words, in the entire absence of a
circulation. That such a secretion continues no longer
than it docs is not strange, for in the end all the constituents
of a secretion, not the least important of which is the water
itself, must be obtained from the blood. The increased blood-
pressure, which has so often and so long been considered the
determining factor in increasing the amount of the salivary as
well as the amount of other secretions, can by itself be of
little moment, as is shown by Ludwig's classical observa-
tion. When the outflow of saliva from the salivary duct
is prevented, the pressure in this duct may, when the chorda
tympani is stimulated, rise far above that found in even
the larger arteries, such as the carotid. Finally, it is pos-
sible to bring about a vascular dilation in a salivary gland and
yet get no secretion. This happens when, after a dose of
atropin, the chorda tympani or the auriculo-temporal nerve
is stimulated. The converse of this experiment can be
performed with pilocarpin. When this alkaloid is injected,
a free flow of saliva is brought about, even when no change
has occurred in the calibre of the blood-vessels.

Besides the change which occurs in the calibre of the
blood-vessels supplying a salivary gland, there is also a
change in temperature. The active gland becomes warmer.
The amount of thermal change is not determined simply
by the arterial blood coursing through the gland. As
Ludwig and Spiess have shown, when one thermometer is
inserted into the secretory duct of the submaxillary of a
dog, a second into the efferent vein, and a third into the
carotid artery, then, when the gland is excited to secretion
by stimulation of the chorda tympani, the thermometers
in the duct and in the vein register a higher temperature
than the thermometer in the carotid. This observation is
of fundamental importance, as it gives us some clue to the
character of the changes which occur in salivary and

182 PHYSIOLOGY OF ALIMENTATION.

other glands during activity. Such a rise in temperature
means that exothermic reactions are taking place within
the gland. These exothermic reactions may be chemical,
and we find support for this idea in the well-known fact
that an active salivary gland consumes more oxygen and
gives off more carbon dioxide than a resting one. We are
dealing therefore with oxidations in the gland. But from
Mathews' experiments we know that lack of oxygen increases,
at least within certain limits, the secretions of the salivary
glands. Under such circumstances the heat would have to
come from intramolecular oxidations, in other words, from
the analysis of complex compounds into simpler ones. We
meet with less difficulty if we seek the source of at least
part of the heat that is set free in certain physical changes.
Of primary importance in this connection is the well-known
fact, which Pauli has studied with particular care, that col-
loids in absorbing water set heat free. The swelling of
mucin and other colloids found in saliva might well there-
fore be considered as sources of heat. Mathews' observa-
tions would also find an explanation, for an accumulation
of carbon dioxide or the various poisonous substances formed
in living tissues in the absence of oxygen all increase the
affinity of tissues for water.

We have yet to mention the paralytic secretion of Claude
Bernard. When both the cranial and sympathetic nerve
fibres passing to a gland are cut, all secretion ceases. After a
few hours the secretion begins once more and continues for
days. Then the secretion falls off again and finally ceases.
Whether the secretion is due to degeneration (and supposedly
stimulation) of the nerve and ceases when this is complete,
as is generally believed, or whether the atrophy which the
gland gradually undergoes is the real cause of the cessation,
is not yet settled.

3. The Reflex Secretion of Saliva. — Having determined
the nervous paths over which impulses may reach the salivary
glands and excite them to activity, we have to discover the

THE REGULATION 01 SAL/1 IRY SECRETION. 183

means by which such impulses are made to traverse these
nerves. Jt has been a long-recognized fact that the flow of
saliva, which, under ordinary circumstances is not more than

sufficient to keep the mouth comfortably moist, is enormously
increased as soon as sweet, bitter, or dry substances are taken
into the mouth, a piece of rubber is chewed, or the mind
dwells for a few seconds upon the enjoyment of some food.
That so many and such diverse stimuli are capable of bring-
ing about an increased flow of saliva has naturally led to the
conclusion that any stimulus is effective in this direction.
This is, however, not the case, as can be shown very well on
dogs having permanent salivary fistulae, operated on as de-
scribed in the first section of this chapter.

A mechanical stimulus is either unable to bring about a
flow of saliva, or at the best the secretion of only a few drops.

If some pebbles are thrown to a dog from some distance,
so that the mechanical stimulus is fairly strong, he catches
them, may move them about in his mouth, even swallow a
few of them, and yet no saliva flows. Or if ice-water is poured
into the mouth, or some snow is thrown in, no saliva flows.
But let some sand be thrown into the mouth and the saliva
flows in quantities. The same is true of all substances which
the dog rejects — acids, alkalies, salts, or bitters. There
seems, therefore, to be a purposeful element in the secretion
of the saliva, for it does not flow when substances which do
not need it, such as water, are taken into the mouth, but it
does as soon as substances which are to be rejected, or which
need to be neutralized, diluted, or washed out of the mouth
are taken. The degree of dryness of the food determines
the amount of saliva poured out upon it — the drier the food
the larger the amount of saliva that is secreted. This pur-
poseful element seems still more striking when it is found,
as experiment shows, that a thin and watery saliva is always
poured out upon substances which are to be rejected, while
upon edible substances a saliva rich in mucin, one, therefore,
which lubricates the bolus to be swallowed and facilitates

184 PHYSIOLOGY OF ALIMENTATION.

its descent through the oesophagus, is s< ireted. Still,
great care must be exercised in looking upon every re-
action of an organism, or one of its organs as eminently pur-
poseful (as does Pawlow1), and therefore for the ultimate
good of the organism. We are familiar with too many illus-
trations of the fact that living matter may possess character-
istics that are eminently dangerous to its life and well-being.

Of much interest is the connection between the physi-
ology and what may be called the psychology of the salivary
glands. We see in the facts about to be discussed a strik-
ing illustration of how the organic functions of an organ may
be markedly influenced through the state of the mind — an
illustration not without interest to the clinicist. The same
series of reactions can be obtained as have been described
above, when the animal's attention is simply directed to the
substances in question. When the experimenter simply pre-
tends to throw pebbles or snow into the mouth of the dog no
secretion follows, but the saliva flows copiously if sand takes
the place of the pebbles. If various kinds of food are offered
the animal, saliva flows or not, just as though the animal had
been really feed them. Moreover, the same qualitative varia-
tions are noted in the saliva. If the proffered food is dry,
much watery saliva is secreted, while a slimy saliva less in
amount is poured out when meat is offered.

Brief mention must now be made of the paths over which
impulses travel to the cranial and sympathetic nerve fibres
which supply the salivary glands and influence their secre-
tions. Both these sets of nerve fibres originate from the
medulla or in the pons and spinal cord just above and below
this. Claude Bernard's experiments are therefore of great
interest, which show that injury to certain portions of the
medulla causes a copious flow of saliva. Whatever means
be employed in bringing about a reflex secretion of saliva,
this can only be possible through impulses passing from

' See Pawlow: Work of the Digestive Glands. Translated by
Thompson, London, 1902, pp. 151 and 152,

THE REGULATION OF SALIVARY SECRETION. 185

the periphery into the medulla, and from here over the various
nerves to the salivary glands. Most of the peripheral stimuli
which call forth a secretion of saliva originate, no doubt,
in the mouth. When food is taken into the mouth, it acts
upon the gustatory nerve and the glosso-pharyngeal, and
these constitute the afferent nerves over which impulses
reach the medulla. But many other afferent nerves exist
which can bring about a flow of saliva. When the sight of
food is effective in this direction, the impulses travel over
the optic nerves into the large nuclei at the base of the brain,
from where, apparently, connection is made with the medulla.
When smell causes a reflex secretion of saliva, the impulses
must reach the uncinate gyrus and from here connect with
the medulla. Of interest is the great flow of saliva which
accompanies feelings of nausea. In certain cases we deal
apparently with a stimulation of the endings of the vagus
nerve over which impulses travel into the medulla. In
others the agencies effective in bringing about the feeling
of nausea (as in sea-sickness) may influence the medulla,
in part at least, directly. The medulla from which the nerve
fibres supplying the salivary glands arise is intimately con-
nected with the cerebral cortex. For this reason the mere
thought of pleasant or unpleasant things may cause a flow
of saliva. As experimental evidence of such a connection we
have the well-known fact that stimulation of certain portions
of the cerebral cortex causes a free flow of saliva.

We have thus far limited ourselves to a discussion of the
three great pairs of salivary glands. The many small glands
scattered throughout the mucous membrane lining the oral
cavity give off no inconsiderable secretion as their contri-
bution to the ordinary mixed saliva found in the mouth
and poured out upon the food. We have little accurate
knowledge, however, regarding the means by which the
secretion from these small glands is ordinarily controlled.
Apparently they arc more or less independent of the ('(Mi-
tral nervous system, for when the ducts of all the large

186 PHYSIOLOGY OF ALIMENTATION.

salivary glands are turned outward, sufficient saliva is still
secreted to keep the mouth moist, and according to Colin
this may amount, even while no food is being chewed, to
from 100 to 150 c.c. an hour in the horse.

4. On the Nature of Salivary Secretion. — The impression
might readily be obtained from the preceding paragraphs
that the secretion of saliva is primarily a nervous act. This
is, of course, not the case, and in the last analysis the secre-
tion of saliva must be regarded as a function of the cells
themselves constituting the salivary glands, only their
activity is markedly influenced through impulses which
pass to them over the nerves connected with them. We
have already mentioned the fact that the salivary glands
will secrete (paralytic secretion) when all the nerves sup-
plying them have been cut. It is much more reasonable
to suppose that this secretion is an expression of activity
on the part of the glands themselves than one induced
through stimuli passing into them from the cut nerves.
In a similar way modern experiments with atropin, pilo-
carpi, and other poisons seem to indicate that their action
is at least not limited to their effect upon the nerves, if per-
haps they do not act solely upon the secreting epithelium itself.

We know as yet nothing definite regarding the nature
of the process of salivary secretion, any more than we know
regarding the forces at work in any process of secretion.
It was once believed that the saliva represented nothing
but a filtrate from the blood which was squeezed through
the gland-cells under the influence of the blood-pressure.
This idea must be given up entirely, for the chemical com-
position of the saliva differs from that of blood-plasma
or lymph, not only quantitatively but also qualitatively.
Certain salts are present in greater, others in less amount
than in the blood, and while some chemical constituents
found in the blood do not appear at all in the saliva, the
reverse is also true. We must therefore conclude that the
gland cells themselves have the power of forming new chem-

Till-: REGULATION OP SALIVARY SECRETION. 187

ical compounds from those brought them in bhe blood, and
secondly a power of selection in that they lake out of the
blood and secrete into the salivary duels only certain of
the constituents of the blood-plasma. How little the blood-
pressure hi/ itself is of any importance in these processes of
secretion is indicated not only by the facts already cited,
tliat an increase in blood-pressure need n<>( be followed by
an increased secretion and vice versa, but also by Ludwig's
classical observation. If one mercury manometer is tied
into Wharton's duct, while another is connected with the
carotid artery, and the chorda tympani nerve is stimulated
electrically in order to bring about a secretion of saliva,
the pressure registered in the salivary duct may be 100 to
200 mm. higher than that in the arter}^. It is possible that
osmotic forces brought into play through a breaking down
of complex molecules into simpler ones may explain a part
of the phenomena observed, but it seems much more prob-
able that the great pressures produced through the swelling
of colloids (such as mucin) in water are chiefly responsible.
Not only are colloids having a great affinity for water pro-
duced in the salivary glands, but histological evidence is
at hand to indicate that during secretion those portions of
the gland-cells lying farthest - from the nucleus suffer the
greatest changes in size. Since the nucleus is intimately
connected with processes of intracellular oxidation, it is
conceivable that in those portions of the cell lying nearest
the lumen substances are formed which particularly favor
the imbibition of water by the colloids formed in the cells.
In this way the cells at first increase in size, and pres-
sures are produced which serve to squeeze certain por-
tions of the cell contents (the saliva) into the glandular
ducts. Finally, it is nol impossible thai substances capable
of swelling may be secreted into the smaller salivary duots
and that the pressures registered in the manometer con-
nected with the main salivary duct may be due, in pari at
least, to the subsequenl swelling cf these substances.

CHAPTER XI.
THE REGULATION OF GASTRIC SECRETION.

I. Gastric Fistulae. — For our earliest knowledge of the
secretion of gastric juice by the stomach, and its qualitative
and quantitative variations under different physiological
conditions, we are indebted to the American physician Beau-
mont. Beaumont made his observations upon the hunter
Alexis St. Martin, who retained, in consequence of a gun-
shot wound, a permanent opening in the abdominal wall
which led directly into the stomach.

An attempt to reproduce the same condition of affairs
in animals led to the experiments of more modern observers,
who created gastric fistulse artificially in animals of various
kinds. The results obtained, however, were by no means
harmonious or satisfactory. The animals sickened and died,
or at the best secreted a juice" which was evidently subnor-
mal, both in quantity and quality. In order to obtain a
flow of gastric juice, Beaumont introduced into the stomach
of his patient various kinds of food. The students of gas-
tric physiology who immediately followed him used the same
methods, and we still use them today in the clinical exam-
ination of the gastric juice. A patient is fed a specified
diet and the gastric contents, which are subsequently re-
moved through introduction of a stomach-tube, are sub-
jected to chemical analysis. This procedure does not, how-
ever, yield a pure juice, but one mixed with food particles,
saliva, etc.

The first to try to obtain pure gastric juice was Klemen-

188

THE REGULATION OF GASTRIC SECRETION. 189

si i:\vicz,1 who in 1875 followed the principle adopted byTinuv
for the intestine, and attempted the isolation of a part of
the stomach into a closed pouch which opened externally.
His dog lived, however, only three days. IIkimaii aix 2 soon
after repeated the operation and succeeded in keeping his
animal alive. Pure gastric juice can be obtained from a
dog operated upon in this way. It is only necessary to
introduce food into the large stomach, when a flow of per-
fectly pure gastric juice will take place from the isolated
cul-de-sac.

The operation of Heidenhain possesses the important
defect of interfering with the nerve-supply of the stomach.
To overcome this objection Pawlow and Chigin 3 have
devised an operative procedure which will be described
in some detail, as its use has done much to give us a clearer
insight into the physiology of the stomach. An incision is
made into the stomach, which begins in the fundus a little
below the pylorus and runs longitudinally toward the car-
dia. This incision divides both anterior and posterior
walls (AB, Fig. 20, I). The triangular flap thus formed
is made into a cylinder, the orifice of which is sewed into
the abdominal wall, while its base is still connected with
the main cavity of the stomach. The cavity of the stomach
and that of the pouch do not, however, communicate with
each other, but are separated by a septum of mucous mem-
brane, as indicated in Fig. 20, II. The opening in the main
stomach cavity is closed by a line of sutures.

In order to obtain gastric juice from the miniature stomach
(S, Fig. 20, II) a small India rubber or glass tube, freely
perforated at its lower end, is introduced through the opening
in the abdominal wall (AA) into the pouch. The tube remains

1 Klemensiewicz: Sitzungsberichte d. Wiener Akad., 1N75, Bd.
LXXI.

2 Heidenhain: Pniiger's Archiv. 1878, XVIII, p. 169.

3 Pawlow and Chigin: Pawlow's Work of (he Digestive Glands.
Translated by Thompson, London, 1902, p. 11.

190

PHYSIOLOGY OF ALIMENTATION.
I

Oesophagus

Fig. 20.

(Copied from PaWlow: Work of the Digestive Glands. Trans, bj

^Thompson, London, 1902, p. 12.)

THE REGULATION OF GASTRIC SECRETION. 191

in the pouch of its own accord, or may be fastened there by
an clastic band encircling the body of the animal. Juice is
collected while the animal is lying down or is supported in
an erect position in a suitable frame.

It is only necessary to add that the miniature stomach
gives a true picture of the secretory activity of the large one
(V), even though food does not at all enter the small cavity.
This has been proved by a long series of carefully conducted
experiments, in which the quantity and quality of the juice
poured out in the large cavity has been compared with
that poured out in the isolated cul-de-sac.

We have yet to describe an operative procedure which
is made use of in sham feeding, and upon which several
physiological facts concerning the stomach and its activity
are based. In 1889 Pawlow and Schumow-Simanowski
performed the operation of oesophagotomy on a dog already
possessing a simple gastric fistula. The oesophagus is
divided in the neck, and the divided ends are made to
heal separately into the angles of the skin incision. This
separates the stomach and mouth entirely. Dogs operated
upon in this way recover and continue in excellent health
for years afterward. To keep such animals alive, food must,
of course, be introduced directly into the stomach.

The following experiment shows how pure gastric juice
can be obtained from such an animal. If the dog be
given meat to eat, the food drops out again from the
lower extremity of the upper segment of the divided oesoph-
agus. But the perfectly empty stomach begins to secrete
gastric juice and this continues as long as the sham feeding
is kept up. As will be shown in detail later, this is a psychic
secretion of gastric juice. Suffice it for the time being to
state that several hundred cubic centimeters of pure, gastric
juice may be obtained daily in this way without injury to
the dog.

CEsophagotomy may be combined with the already de-
scribed operation of Pawlow and Chigin fur the separation

192 PHYSIOLOGY OF ALIMENTATION.

of a miniature stomach from the large. This and other
operative variations in the experiments and the deductions
which may be drawn from them are given below.

2. The Effect of Diet on Gastric Secretion. — The experi-
mental methods of Pawlow, Schumow-Simanowski, and
Chigin described above have answered for us a number of
questions connected with the secretion of the gastric juice
which the older methods could only hint at. Thanks to the
ingenious combination of an cesophagotomy with a simple gas-
tric fistula, and the clever surgical procedure which allows the
separation of a miniature stomach opening externally from
the main stomach, the secretory activity of this organ may
be followed in great detail.

The stomach of the fasting animal is entirely empty. The
secretion of gastric juice is dependent upon the taking of
food. This can be shown very nicely in a dog possessing an
isolated miniature stomach. While fasting, this is entirely
empty, but within a few minutes after food is given to the
animal it begins to secrete. The quantity of juice secreted is
almost exactly proportional to the amount of food ingested.
Chigin gives the following values to corroborate this state-
ment:

100 gms. meat 26.0 c.c. gastric juice

200 " " 40.0 c.c. " "

400 " " 106.0 c.c. "

When, instead of the above, various amounts of a mixed diet
made up of meat 50 gms., bread 50 gms., milk 300 c.c. are
given, the same fact is brought out.

The above mixture yielded 42.0 c.c. juice.

Twice the above mixture yielded 83.2 c.c. juice.

The gastric secretion is not all poured out at once upon the
food, but continues as long as food remains in the stomach.
The rate of the secretion varies, however, from hour to hour.
The secretion reaches its maximum within the first hour,

THE REGULATION OF GASTRIC SECRETION. 193

after which it decreases steadily in amount until at the
end of a number of hours ii has fallen to the zero-mark once
more. The cause of this decrease is perhaps explained by
the gradual den-cast" in the amounl of food undergoing diges-
tion in the stomach. The following experiments of Chigin
illustrate the above:

Rate of Gastric Secretion after Feeding 100 Cms. Meat.

Hour after feeding. Quantity of juice in c. c.

Exp. a. Exp. 6.

1 11.2 12.6

2
3
4
5

These values are represented graphically in the following
curves (Fig. 21).

8.2

8.0

4.0

2.2

1.9

1.1

0.1

a drop

Total. . .

. . 25.4

23.9

HOUFu

1

2

3

4

."

1

o

d

4

5

12

10

d

d 8

z

•" c

O ()

3
—>

4

k

n

/

Fig. 21. — Curve of secretion of gastric juice after a meal of meat.

Two experiments.

(Copied from I 'aw low: Work of t lie nicest ive ('.lands. Trans, by

Thompson, London, L902, p. 23.)

Pawlow and Chigin's miniature stomach allows also a
study of the qualitative variations in the gastric juice under

194 PHYSIOLOGY OF ALIMENTATION.

different conditions of diet, etc. To do this the animal is
fed in the ordinary way, and the secretion which pours out of
the miniature stomach is collected, measured, and used for
analysis. It was pointed out above that the secretions of
this small stomach are identical with those of the large.

The following table indicates how the digestive power of
the gastric juice varies during the period of digestion, after a
single feeding of 400 gms. of meat.1 The cause of these
variations is not entirely clear, in fact their very existence
is questioned by some observers. The digestive power is
expressed in terms of millimeters of coagulated egg-albumin
digested out of capillary tubes in the unit of time. (Mett's
method of determining proteolysis quantitatively.)2

Hour after feeding. Mm. of egg-albumin digested.

1

2
3
4
5
6
7
8

These figures are plotted in the form of curves in the follow-
ing illustration (Fig. 22).

The digestive power of the gastric juice, which Pawlow and
his pupils look upon as an expression solely of the amount of
ferment (this is certainly erroneous) contained in the juice,
does not vary with the amount of juice secreted in the unit
of time. A strong digestive power may be found, not only
when the secretion is scanty but also when it is copious.

So far as the inorganic constituents of the gastric juice are
concerned, Pawlow believes that the concentration of hydro-

1 Lobassoff: Pawlow' s Work of the Digestive Glands. Translated
by Thompson, London, 1902, p. 29,

2 See p. 130.

Exp. a

Exp. b.

6.0

5.8

4.3

4.1

3.4

3.4

3.5

3.0

3.8

3.8

3.0

3.1

3.6

3.5

3.9

4.5

THE REGULATION OF GASTRIC SECRETION.

105

chloric acid never varies. This applies, however, only to the
gastric juice as it is poured out by the glands. Once the juice
has left the crypts of the gastric mucosa, its acidity may be
reduced through various agencies, and it is to these that the
fluctuations in the acidity of the gastric juice under various
physiological and pathological conditions must be attributed.
The mucus secreted by the stomach-wall has the power of
neutralizing the acid of the gastric juice. For this reason

RS

0.0
5.0

} :? 4

'> 0

8

12 3 4

I

> G

B

i

L0

8.0

2.0

1.0

il

Fig. 22. — Digestive power of hourly portions of gastric juice after a

meal of 400 gms. of meat.
(Copied from Pawlow: Work of the Digestive Glands. Trans, by
Thompson, London, 1902, p. 28.)

the first juice collected from the stomach of a fasting dog
always has a lower acidity than later specimens, for the
empty stomach is covered with a layer of mucus. Also, the
more rapidly gastric juice is secreted the higher is its acidity,
for in this way less time is allowed for the neutralization of
the hydrochloric acid through the gastric mucus. Finally,
the power of the saliva which enters the stomach to neu-
tralize the acid secreted there must also be borne in mind.

The gastric juice poured out upon different kinds of food
varies not only in quantity but also in quality. The ex-
periments of some of the older observers lend support to
this idea, but their results cannot be looked upon as en-
tirely free from criticism. The results of Pawlow and his

JUICE IN c.c.

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THE REGULATION OF GASTRIC SECRETION. 1^7

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198 PHYSIOLOGY OF ALIMENTATION.

pupils are perhaps more trustworthy. The average variation
in the ferment content (better digestive power) of the juices
poured out when equal weights of bread, meat, or milk are
fed, expressed in terms of millimeters of coagulated egg-
albumin digested out of capillary tubes in the unit of time,
is shown in the following table:

Bread 6 . 64 mm.
Meat 3.99mm.
Milk 3.26 mm.

Since the amount of proteolytic ferment contained in
the compared juices is proportional to the square of the
rapidity of digestion, we find upon calculation that the juice
poured out upon bread contains four times as much acid-
proteinase as that poured out upon milk and about three
times as much as that poured out upon meat, for the squares
of the figures given in the above table stand as 44:16:11.

The quantitative variation in the secretion of the gastric
juice (expressed in cubic centimeters) when different foods
are given is indicated in the following experiment of Chigin;
the digestive power of the juices (expressed in millimeters
of digested egg-albumin) is given in the parentheses follow-
ing these values.

Quantity and Quality of Gastric Juice Seceeted upon Feeding.

Hour. 200 gms. meat. 200 gms. bread. 600 c.c. milk.

1

11.2(4.94)

10.6(6.10)

4.0(4.21)

2

11.3(3.03)

5.4(7.97)

8.6(2.35)

3

7.6(3.01)

4.0(7.51)

9.2(2.35)

4

5.1 (2.87)

3.4(6.19)

7.7(2.65)

5

2.8(3.20)

3.3(5.29)

4.0(4.63)

6

2.2(3.58)

2.2(5.72)

0.5(6.12)

7

1.2(2.25)

2.6(5.48)

...(.. .)

8

0.6(3.87)

2.6(5.50)

...(....)

9

...(....)

0.9(5.75)

...(....)

10

...(....)

0.4(....)

...(....)

The values are represented graphically in Figs. 23 and 24.
Each kind of food seems to bring about a definite hourly

THE REGULATION OF GASTRIC SECRETION. 199

rate of secretion and a characteristic alteration in the prop-
erties of the juice. With a meat diet the maximum rate
of secretion occurs during the first or second hour, during
which periods the quantity of juice secreted is approxi-
mately the same. With bread the maximum secretion
occurs during the first hour, while with milk it occurs dur-
ing the second or third hour. The juice has the greatest
digestive power during the first hour when meat is fed,
during the second and third when bread is given, and during
the last hour when milk is the food furnished the dog.

As the gastric juice acts chiefly upon the protein con-
stituent of the food, Pawlow has made an interesting cal-
culation of the comparative work done by the stomach in
digesting the three articles of food mentioned above, taking
into consideration the nitrogen content of the foods and the
quality and quantity of gastric juice poured out upon them.
He finds that the number of ferment units (obtained by
multiplying the squares of the numbers representing the
digestive strengths by the number of c.c. poured out upon
the food) required for the digestion of corresponding nitro-
gen equivalents in the different kinds of food is as follows:

Bread 1600 units
Meat 430 "
Milk 340 "

This means that protein in the form of bread requires
five times more acid-proteinase for its digestion than is
poured out upon the same amount of protein in milk, and
that the protein of meat requires a fourth more than its
equivalent contained in milk. Now it is known that vege-
table proteins are much less easily digested than those of
meat, and these less than those of milk. The different
kinds of proteins seem, therefore, to call forth the secretion
of quantities of ferment which correspond with the differ-
ences in their digestibility.

The concentration of the hi/drochloric acid in the gastric
juice also varies with the different kinds of food. It is

200 PHYSIOLOGY OF ALIMENTATION.

greatest when meat is fed (0.56 percent HC1) and lowest
when bread is given (0.46 percent HC1). A milk diet gives
an intermediate figure.

3. The Relation of the Nervous System to Gastric Secre-
tion.— The relation of the nervous system to the secretion
of the gastric juice by the stomach has for many years been
the subject of debate. Against the well-known clinical
fact that emotional states, injuries of various kinds, etc.,
profoundly alter the activity of the stomach stood the
observations of a score of experimenters who were able to
prove no direct connection between the central nervous
system and the digestive organ. In 1852 Bidder and
Schmidt published the fact that the mere sight of food
will call forth a secretion of gastric juice in the dog, and
in 1878 Richet demonstrated on a patient gastrotomized
for an incurable stricture of the oesophagus that a secre-
tion of gastric juice occurred whenever the patient took
certain articles of food into the mouth. The efforts, how-
ever, to show the paths of nervous connection in these cases
were singularly unsuccessful. In recent years, however,
Pawlow and his coworkers Schumow-Simanowski, Jur-
gens, and Ssanozki, in a series of beautiful experiments,
have been more fortunate, and, thanks to their researches,
we are now familiar with the cause of failure in the older
experiments, and may look upon the connection between
central nervous system and stomach as experimentally
proved and the nervous paths constituting this connection
as fundamentally established.

The following experiment shows that the effect of feeding
is transmitted to the gastric glands through nervous channels
and that one of these channels is the vagus nerve.1 A dog,
possessing an ordinary gastric fistula and cesophagotomized
as described above,2 so that the mouth is entirely cut off

'Pawlow: Work of the Digestive Glands. Translated by Thomp-
son, London, 1902, p. 50.
2 See p. 191.

THE REGULATION OF (iASTUIC SECRETION. 201

from communication with the stomach, is used. In addi-
tion the right vagus nerve is divided below the recurrent
laryngeal and cardiac branches, at Hie lime that the
gastric fistula is made. No juice (lows from the gastric
fistula in such a dog. If now sham feeding is indulged
in, that is to say if the dog is fed food which it swallows
but which never reaches the stomach, because the swallowed
masses drop out of the oesophageal opening in the neck,
a stream of gastric juice, which steadily increases in volume,
appears at the gastric opening within five minutes after
the dog is given its first food. As long as the dog is fed,
which may be two or more hours, often even five or six,
the gastric juice continues to pour out of the fistula. In
this way several hundred cubic centimeters of juice may
be collected.

How is this effect of feeding carried from the mouth to the
stomach? If the food is taken away from the dog in the
experiment just described, the secretion of gastric juice con-
tinues for several hours, gradually becoming less in quantity.
The right vagotomy threw out of function only the pulmon-
ary and abdominal branches on the side operated upon while
the laryngeal and cardiac fibres were left intact. If now the
left vagus nerve, wdiich has been laid free in the neck by
operation some three hours before the sham feeding is to be
indulged in, be carefully drawn out of the wound and divided
with a snip of the scissors, the pulmonary and abdominal
branches of both vagi are paralyzed. The preservation of
the laryngeal and cardiac fibres on the right side, however,
prevents the symptoms of cardiac and laryngeal distress
which follow division higher in the neck. If food be now
given this dog a second time, it eats greedily as before, but, in
sharp contrast to the preceding sham feeding, not a single
drop of gastric juice Hows from the stomach. Indeed, never
again in such a double vagotomized dog, even if it lives for
months afterwardj as some of (hem do, docs a sham feeding
call forth a secretion of gastric juice.

202 PHYSIOLOGY *OF ALIMENTATION.

When sham feeding no longer produces a secretion of gastric
juice after double vagotomy, it does not mean, however, that
the gastric glands have lost the power of secretion. As will
be shown later, highly active juice can, under appropriate
circumstances, still be obtained from this digestive organ.
The above experiment only shows that certain exciting in-
fluences which normally, in the ordinary process of eating,
reach the gastric mucosa by way of the vagi have been
removed. As has been shown by Ketscher, the mode of
feeding and the character of the food presented to the dog
during sham feeding alters markedly the character of the
gastric juice obtained. If the dog is given pieces of meat at
long intervals, less gastric juice and one lower in digestive
power is obtained than when the dog is fed more rapidly.
In a similar manner, a diet of meat, which the dog relishes
highly, produces more juice and one having a higher digestive
power than a meal of bread, which the dog relishes less.

The existence of nerve fibres in the vagus which influence
the secretion of gastric juice was proven above by showing
that after division of both vagi stimulation of the buccal
cavity with food no longer excited the gastric mucosa to
activity as before. It can, however, be shown by direct
stimulation of the vagus in a properly performed experiment,
that this nerve contains fibres which influence the activity
of the stomach. This has been accomplished by Pawlow and
Schumow-Simanowski. A gastrotomized and cesophagot-
omized dog, in which the right vagus nerve has been cut below
the origin of the inferior laryngeal and cardiac fibres, is used
for the experiment. Three or four days before stimulation
of the vagus is to be carried out, the left vagus is carefully
dissected out in the neck, a ligature passed around it but not
tied, and the whole carefully preserved under the skin. On
the day the vagus stimulation is to be carried out, the wound
is painlessly opened and the nerve laid bare. By attending
to these details, whereby appreciable pain to the animal is
avoided, excitation of the vagus by induction shocks at in-

THE REGULATION OF GASTRIC SECRETION 203

tervals of one or two seconds invariably yields a secretion of
gastric juice from the stomach. The negative or at best
uncertain results of the older observers upon stimulation
of the vagus are probably all to be explained by the fact thai
their animals were under the influence of anaesthetics or in
pain, and, as will become apparent when the pancreatic
secretion is described, peripheral stimuli of various kinds
inhibit markedly the activity of the digestive glands. When
all peripheral stimuli are prevented from inhibiting reflexly
the activity of the stomach (this can be done by dividing the
spinal cord just below the medulla oblongata), the vagus
nerves ma)' be laid bare in the neck and stimulated at once,
when a secretion of gastric juice will be observed. In this
way Uschakoff has succeeded in demonstrating, in an experi-
ment performed at one sitting, the relation of the vagus nerve
to the stomach.

Both forms of experiment, the "chronic " as well as the
"acute," show, therefore, that the vagus nerve contains fibres
which influence the secretion of the gastric glands. As will
be shown later, however, a secretion of gastric juice occurs
also when the vagi are cut; this indicates that the integrity
of the vagus is not the only requisite for the secretory activity
of the stomach. Under normal circumstances, however, these
nerves play the already described exceedingly important role
in the initiation of the gastric flow.

4. The Appetite as an Excitant of Gastric Secretion. —
It was shown in the preceding paragraphs that the vagus
nerve has a marked influence upon the secretion of juice by
the stomach. We have now to answer the question, How
is the vagus nerve normally excited? An explanation which
first suggests itself is that we are dealing with a reflex excita-
tion of the gastric mucosa, brought about through a stimula-
tion of nerve endings in the mouth and carried from here to
the vagus centre in the medulla, and from there down-
ward to the stomach. This idea has been carefully tested
experimentally by PAWLOwand found to be incorrect, as shown

204 PHYSIOLOGY OF ALIMENTATION.

by the following facts. The food upon entering the mouth is
able to stimulate the buccal mucous membrane, either chem-
ically, mechanically, or in both of these ways. Application
of such substances as acids, salts, bitters, pepper, mustard,
etc., to the mucous membrane of an cesophagotomized dog
never calls forth a secretion of gastric juice, however. Not
even does a meat decoction in most instances prove effective
in this regard. Nor does a combination of mechanical stimu-
lation with the chemical, such as wiping out the mouth with
an acid-soaked sponge, or giving the dog stones to swallow,
work any more successfully in exciting the gastric mucous
membrane. The stones drop out of the oesophagus, and,
even if this play is kept up for hours, not a drop of gastric
juice flows from the gastric fistula. As soon, however, as
the old experiment of sham feeding is tried, and meat or bread
is given the dog instead of stones, a free flow of gastric juice
begins in five minutes and steadily increases in amount as
described above. These facts prove clearly that the nerves
of the stomach are not excited reflexly through chemical or
mechanical stimulation of the buccal mucous membrane.
Wherein then does the sham feeding with food differ from
that with stones? In the former case the dog eagerly de-
sires its meal, something which is lacking in the latter. This
eager desire for food, the appetite in other words, is the excitant
of the gastric flow, and we must conclude in consequence that
a psychic state rather than a reflex from the mouth acts as
the normal excitant of the vagus nerve and the gastric mucosa
at the beginning of a meal.

Bidder and Schmidt observed years ago that merely offer-
ing a hungry dog food excited a flow of gastric juice. Paw-
low has confirmed and elaborated this experimental finding.
Actual sham feeding with food does not need to be indulged
in in order to obtain a flow of gastric juice. If only a tempting
meal be prepared before a hungry dog, a flow of gastric juice,
such as has been described when sham feeding is practised,
begins within five minutes after the teasing is begun. In

THE REGULATION OF GASTRIC SECRETION. 205

fact it has been shown experimentally by Ssanozki that
merely tempting a dog with food often leads to a greater secre-
tion of gastric juice in the unit of time than the actual sham
feeding.

The "appetite juice" varies both in quantity and quality.
The more eagerly a dog eats the greater the amount of juice
and the higher the digestive power. A good appetite at the
beginning of a meal is, therefore, equal to a copious secre-
tion of strong gastric juice.

5. The Physiological Importance of the Appetite Juice. —
It was shown above that the secretion of gastric juice during
the first hour is practically the same for meat or bread, and
that only subsequently the amount and quality of the gastric
secretion varies with the nature of the ingested food. When
only sham feeding with these same foods is indulged in, we find
that the secretion of juice for the first hour is the same as
though the dog had been actually fed. All this indicates
that the first outpouring of juice into the stomach at the
beginning of a meal is the consequence of the psychic excita-
tion. The truth of this statement is still further borne out
by the fact that when a food is given the dog which does not
interest him to the same degree as meat or bread, — for example,
milk, — this initial rise in the quantity and quality of the gas-
tric juice does not appear. While 12.4 c.c. of gastric juice,
having a digestive power of 5.43 mm., are poured out upon
meat, and 13.4 c.c, having a digestive power of 5.37 mm.,
are poured out upon bread during the first hour after feeding,
only 4.2 c.c. of a digestive power of 3.57 mm. are poured out
upon milk (Chigin). That the mere act of taking food in-
creases both the quantity and quality of the gastric juice
is still further supported by the observation of Kotljar and
Lobassoff, who found that when an ordinary meal is divided
into several portions, and these are fed at intervals of three
hours, an increase in the quantity and quality of the juice
immediately follows each installment.

The role of the appetite juice can be still more clearly

206

PHYSIOLOGY OF ALIMENTATION

Hours after feeding
2 3

12

10

6 8

2 6

11|

ti

A B

Fig. 25.

A = ordinary curve of gastric secretion.

B= curve from direct introduction of food into stomach.

demonstrated by comparing gastric digestion in which it is
allowed to play a part, with gastric digestion in which the
psychic element is shut out. This can be readily done in an
cesophagotomized dog which possesses a fistula leading into
the main stomach in addition to having a gastric cul-de-sae.
If food is introduced into such a dog's main stomach
without attracting its attention, it is found that digestion
goes on at an entirely different rate than when the psy-
chic element is allowed to play a part. Under these cir-
cumstances, bread and coagulated white of egg do not yield

THE REGULATION OF GASTRIC SECRETION. 207
12 3 1 2 :; 4

Fig. 25.

C= curve from sham feeding.
D= summation of B and C .
(Copied from Pawlow: Work of the Digestive Glands.
Thompson, London, 1902, p. 82.)

Trans, by

a single drop of juice for an hour or more afterward and the
introduction of meat yields a gastric secretion only after a
considerable period of delay. It begins in the latter case in
15 to 45 minutes after feeding, instead of 6 to 10 minutes as
normally, and when it does flow is poorer, both in quantity
and quality, than under normal circumstances. In the accom-
panying figure (Fig. 25), curve .1 shows the ordinary course
of gastric secretion following a meal of 200 gms. of meat;

208 PHYSIOLOGY OF ALIMENTATION.

curve B that obtained when the same amount of food is
introduced into the stomach directly, and curve C the result
when sham feeding with the same is indulged in. D is a
synthetic curve produced by adding B and C and approxi-
mates closely curve A. As can readily be seen, the introduc-
tion of food into the stomach directly does not lead to as rapid
or as great a secretion of gastric juice as does the normal
process of feeding. But if the quantities obtained by intro-
ducing the meat into the stomach be added to those ob-
tained by sham feeding a curve almost identical with the
normal results.

The importance of the psychic element in gastric digestion
can be demonstrated still more strikingly by the following ex-
periment of Lobassoff on two cesophagotomized dogs pos-
sessing ordinary gastric fistulse. If a definite number of
pieces of meat threaded on strings be introduced directly into
the stomach of one dog while its attention is being distracted
by patting and talking kindly to it, and an equal number of
pieces are introduced into the stomach of another dog, but
during the process a vigorous sham feeding is kept up, the
following differences are noted. Two hours after 25 pieces
weighing 100 gms. in all had been fed to each of the dogs,
the dog without sham feeding had digested 6.5 percent,
the one with sham feeding for eight minutes, 31.6 percent,
as shown by subsequent weighing of the undigested food ex-
tracted from the stomach. In another experiment, in which
the meat had remained for five hours in the stomachs, 58
percent had been digested without sham feeding, while. 85
percent had been digested with sham feeding. These figures
leave no room for doubt of the great importance to be attached
to the eager desire for food, in other words to the appetite.

6. Other Excitants of Gastric Secretion. — It must not
be believed from the foregoing that the appetite is the only
excitant of gastric secretion. This is shown not only by
the observation that a secretion of gastric juice occurs when
the psj^chic element is allowed to play no part at all, as

THE REGVLAT10S OF GASTRIC SECRETION. 2()9

when the food is introduced into the stomach directly, but
also by the fact that the effect of sham feeding does not last
as long as an ordinary digestive period nor yield in the later
hours, of this period as active a juice as is obtained after a
true meal. What, then, are the other excitants of the gastric
How besides the appetite which we have seen above plays so
important a role in digestion? We think naturally of the
mechanical stimulation and secondly of the chemical stimu-
lation which might be brought about by the presence of the
food in the stomach. Let us first see if mechanical stimu-
lation is effective in bringing about a secretion of gastric
juice from the stomach.

Almost without exception the older observers believed that
mechanical stimulation of the gastric mucosa by a feather
or a glass rod would yield at least some secretion of gastric
juice. Within recent years, however, this question has been
investigated by Pawlow and his coworkers, who have pointed
out the sources of error in the older experiments, and today
we say that mechanical stimulation is ineffective in bringing
about a secretion of gastric juice. This is shown by the follow-
ing experiment.1

In an oesophagotomized dog possessing a gastric fistula
the stomach is first thoroughly washed out with water. If
the mucous membrane is now mechanically stimulated by
moving a feather or a glass rod over it continuously for a
half hour or more, or if a stream of fine sand is blown against
it, or finally, if the stomach is distended to the size of a child's
head by inserting within it a rubber ball, not a single drop of
gastric juice is discharged. Only a little mucus which turns
red litmus paper blue may be expelled. But let sham feed-
ing with bread or meat be carried out upon the same dog, and
an acid juice appears within five or ten minutes after the
beginning of the feeding. The older observers never obtained

1 Pawlow: Work of the Digestive Glands. Translated by Thomp-
son, London, 1902, p. 86.

210 PHYSIOLOGY OF ALIMENTATION.

through mechanical stimulation a gastric juice which even
approximated the acidity obtained by sham feeding. That
they obtained any acid secretion at all is due to errors in
experiment, such as not washing out the stomach properly,
not waiting until the stimulation to gastric secretion from the
previous meal had entirely worn off, or causing a psychic
secretion of the gastric juice by exciting the dog through the
smell of food on the hands, the appearance of the attendant
who usually fed the dog, etc.

Having settled now that the mechanical properties of the
food are in themselves unable to call forth a secretion of gas-
tric juice we turn to its chemical properties. What chemical
constituents of the food bring about a secretion of juice from
the stomach? In order to investigate this problem a dog
with a miniature stomach, and possessing in addition a fistula
passing into the main cavity, can best be used. The food
undergoing study is introduced into the main cavity, and the
amount and quality of the juice which flows from the isolated
cul-de-sac examined. In order not to bring about a psychic
secretion of the gastric juice, it is best to introduce the food
while the dog is asleep, or while the dog's attention is dis-
tracted from what is going on if the animal is awake.

Water, first of all, has an exciting effect upon the gastric
glands. It has been found by Chigin that when 400 to 500
c.c. of water are introduced into the large stomach of a dog,
a small but constant secretion of juice occurs from the lesser
one. This fact had been previously found by Heidenhain.
Smaller quantities of water are not so effective, and if only
100 to 150 c.c. are injected into the large stomach, usually
no secretion of juice at all occurs. The results are the same
when before the introduction of the water the vagi nerves
are divided below the diaphragm or in the neck.

Neither solutions of sodium chloride, sodium bicarbonate, or
hydrochloric acid excite a flow of gastric juice. According to
Chigin 0.05 to 1 percent sodium bicarbonate solutions, when
introduced in the same amounts as proved effective when

THE REGULATION OF GASTRIC SECRETION. 211

water alone was injected, bring about not even a slight secre-
tion of gastric juice. This salt is, therefore, to be looked
upon as inhibiting the gastric flow, for its presence prevents
the usual exciting effects of the water alone. Oils also have
a distinct inhibitory effect, according to Lobassoff.

Uncoagulated white of egg, whether diluted with water or
not, never brings about a greater secretion of gastric juice
than the same volume of pure water. This is an altogether
unexpected fact, and points to the importance of the appetite
juice in normal digestion. Neither does starch, boiled or un-
boiled and variously diluted, nor grape-sugar, nor cane-sugar,
excite the stomach to secrete juice. Even bread and boiled
white of egg remain for hours in the stomach and excite no
gastric secretion if the psychic element is shut out.

Certain commercial peptones will excite the gastric mucous
membrane directly, but by no means all of them. Pure
peptones do not, however, have this effect. We are in
consequence driven to the conclusion that the commercial
peptones contain as yet unknown chemical substances
which are the real excitants of the gastric flow. Meat broth,
meat juice, and solutions of meat extract act as constant and
active excitants of the gastric secretion. Meat also belongs
in this group, but all these substances bring on a flow of gas-
tric juice much later than when sham feeding is practised.
Whereas the latter method shows a beginning of secretion
after 5 minutes, the former is without effect for 15 to 45
minutes afterward. The majority of foodstuffs does not,
therefore, affect the secretion of gastric juice. To the
minority which is active in this direction, water and cer-
tain as yet unknown constituents of meat belong. The
manner in which these are effective is now to be discussed.

7. Gastric Secretin. — When we study the quantitative
variations in the secretion of gastric juice, we note that
the curve of secretion shows two maximal points. The first
of these is observed immediately after the ingestion of food,
the second two or three hours later. The rapid secretion

212 PHYSIOLOGY OF ALIMENTATION.

which occurs at first is found even when the food never
really enters the stomach, as in sham feeding. Since this
secretion is associated with the passionate desire for food,
or with the mental impressions produced by the sight,
smell, taste, etc., of the food, it is termed the "psychic"
element in gastric secretion. The channel over which the
mental stimulation reaches the stomach and excites the lat-
ter to secretory activity is represented by the vagus nerves.
When these are cut the initial rise in gastric secretion does not
occur. The second great rise in the curve of gastric secretion
following an ordinary meal nevertheless occurs. In what
way is this second rise brought about?

The observations of Edkins 1 give us an answer to this
question. Familiar with the experiments of Bayliss and
Starling on pancreatic secretin,2 Edkins cast about to find
a gastric secretin. His experiments show that under the in-
fluence of certain digestion products the mucosa of the pyloric
end of the stomach produces, during the period of digestion, a sub-
stance—gastric secretin — which is absorbed into the blood and
which excites the gastric glands to increased secretion. To
prove this Edkins prepared extracts of the mucous membrane
of the pyloric end of the stomach by rubbing this up in a
mortar with 5 percent dextrin solutions, or solutions of
various sugars and peptones. If repeated small doses of
this extract are injected into the circulation of a dog which
has had its stomach filled with a physiological salt solution,
it is found at the end of an hour that the salt solution con-
tains both hydrochloric acid and acid proteinase. A secretion
of gastric juice is therefore excited by these extracts. It
can be shown in control experiments in which dextrin, pep-
tone, etc., are injected in pure solution into the circulation
that no hydrochloric acid or acid-proteinase can be found
in the physiological salt solution recovered from the stomach.

1 Edkins: Journal of Physiology, 1906, XXXIV, p. 133; Starling:
Lancet, 1905, CLXIX, p. 501.

2 See p. 227.

THE REGULATION OF GASTRIC SECRETION. 213

We may conclude, therefore, thai l he increased .secretion of
gastric juice, brought about through the injection of extracts
of the mucosa of the pyloric end of the stomach, is due to the
injection of some substance which is produced in this region
of the stomach under the influence of certain of the products
of gastric digestion. This substance is called gastric secre-
tin. The mucous membrane of the fundus of the stomach
does not contain this substance. As to the nature of gastric
secretin but little can be said. It does not seem to belong to
the class of ferments, for it is not destroyed by boiling. In
this regard it is similar to pancreatic secretin.

If now, in the light of the experimental facts which have been
cited above, we try to explain the progress of normal gastric
digestion the following may be said : The initial secretory
period, which is noted after an ordinary meal eaten in the
ordinary way and with desire, is explained by the psychic
effect of eating. This psychic effect lasts for three or four
hours. The digestion periods following this are independent
of the central nervous system and are governed by chemical
agents. In the case of meat we find a reason for the continued
secretion of gastric juice after the initial psychic period in the
chemical constitution of the food itself. It contains sub-
stances which, acting on the mucosa of the pylorus, cause
the elaboration of gastric secretin. The same holds true for
predigested foods — that is, foods containing digestion products
which act in a similar way upon the pyloric mucosa. In the
case of the remaining substances, such as bread .white of egg,
etc., we can say that under normal circumstances the psychic
juice starts their digestion, and in this process chemical
substances are formed which bring about an elaboration of
secretin, and this keeps up the gastric flow after the psychic
element has come to rest. This idea is supported by the fact
that the products of digestion formed in the stomach of one
dog act as excitants of gastric secretion when introduced
into the stomach of another. The clinical application which
may be made of these experimental facts is too evident to

214 * PHYSIOLOGY OF ALIMENTATION.

need much comment. The experiments indicate very clearly
that lack of appetite means lack of gastric juice, which, in
turn, is synonymous with faulty gastric digestion. We see
also the usefulness of predigested foods in certain pathologi-
cal conditions of the stomach and the rational basis for the
use of soups, meat extracts, etc., which, though they have
no food value in themselves, are useful remedial agents, since
they cause a secretion of gastric juice which may be utilized
in digesting otherwise indigestible constituents of a mixed
meal.

CHAPTER XII.
THE REGULATION OF THE PANCREATIC SECRETION.

i. Pancreatic Fistulas.— For the study of the quantitative
and qualitative variations in the secretion of the pancreas
under different physiological conditions various experimental
procedures have been adopted from time to time. The earlier
observers contented themselves with isolating and dissecting
out the pancreatic duct, inserting a cannula into it, and col-
lecting the juice which flowed from it. It was soon found,
however, that the aneesthetic, surgical shock, etc., so affected
the activity of the gland as to stop its secretion altogether,
or at the best allow the flow of only a small amount, and that
not very active pancreatic juice.

In endeavoring to overcome the objections against such a
"temporary" fistula of the pancreas, Claude Bernard and
Ludwig attempted to produce a "permanent" one which
should be free from the immediate effects of an operation.
The former observer tied a glass cannula into the secretory
duct of the pancreas and brought it out through the abdom-
inal wall; the latter used a lead wire to keep the duct patent.
The improved technique did, in fact, yield better results than
the older methods, but in the course of five to ten days the
cannula or wire sloughed out, and further experimentation
was interfered with through infection of the operation wound
and pancreas.

In 1879 Pawlow1 and a year later Heidexhain2 described

1 Pawlow: The Work of (he Digestive Glands. Translated by
Thompson, London, L902, p. 5.

2 IIeidknhain: Hermann's Ilandbuch der Physiologie, Bd. V, p. 177.

215

216 PHYSIOLOGY OF ALIMENTATION.

a surgical procedure for the production of a "permanent"
pancreatic fistula which has stood the test of time, and upon
which our modern knowledge of the activity of the pancreas
is largely based. Pawlow's method is as follows: An oval
piece containing the orifice of the pancreatic duct is cut out of
the duodenum, and the opening in the intestine is closed by a
row of sutures. The isolated piece of intestine is then carried
up into the wound in the abdominal wall and sutured there
with the mucous membrane directed outward. At the end
of two weeks the animals may be used for study. When the
wound has healed, it shows a roundish elevation of the mucous
membrane, in the centre of which the cleft-like orifice of the
pancreatic duct is clearly visible. By supporting the animal
in a suitable frame the pancreatic juice may now be collected
directly into a graduated cylinder as it drops from the duct,
or if the juice tends to spread over the abdominal wall a funnel
may be strapped over the opening of the duct. If only care
be taken to keep the fistulous opening clean, to avoid macera-
tion of the skin by allowing the animal to lie in sand or saw-
dust which absorbs the pancreatic juice, and to supply the
animal with proper food, the dog operated upon in the way
indicated may be kept for months and even years in a healthy
condition.

More recently the operation of Pawlow and Heidenhain
has been much improved by Fodera * who succeeded in caus-
ing a T-shaped metallic cannula to heal into the pancreatic duct.
In this way the pancreatic juice may be collected either ex-
ternally or, by closing the outer opening, be diverted into
the lumen of the intestine. Thus the deleterious effects of
the constant loss of pancreatic juice, necessary in Pawlow
and Heidenhain's operation, is prevented during those periods
when the animal is not being used for experimental purposes.

2. The Effect of Diet on Pancreatic Secretion. — In a dog
in which a pancreatic fistula has been created by either the

1 Fodera: Moleschott's Untersuchungen zur Naturlehre d. Menschen
und d. Tiere, 1896, XVI.

HEGULATIO.X OF Till. PANCREATIC SECRETION. 217

method of I' .\\\ low or lo »i> ki< a, as described above, the quanti-
tative and qualitative variations in the pancreatic juice under
various conditions of diet, etc., can be followed with great
exactness. As was found to be true in the caseof the stomach,
the secretion of pancreatic juice is intimately connected with
the taking of food. The pancreatic secretion, which, during
fasting, amounts to only two or three cubic centimeters in
twenty-four hours, is increased to many times that amount
as soon as food is taken. The secretion from the pancreas is
poured out gradually, though different amounts cuter the in-
testine in each unit of time. The following experiment of
Walther l illustrates this point.

Rate of Pancreatic Secretion after Feeding 600 c.c. Milk.

Hour after feeding. Quantity of juice in c.c.

1

2
3
4
5

These values are expressed graphically in Fig. 26.

Not only does the quantity of pancreatic juice secreted
from hour to hour vary but also the quality. In the follow-
ing table are indicated the hourly variations in the digestive
1 lower of pancreatic juice after a meal of 600 c.c. milk. The
digestive power of the fat-splitting ferment is expressed in
terms of cubic centimeters of a standard barium hydrate
solution, required to neutralize, the acid formed in a given
length of time, when the specimen of pancreatic juice is al-
lowed to act on a fat. The activity of t he proteolyl ic ferment
is determined by Mett's method. That of the amylolytic
ferment is determined by an analogous method, in which
colored starch paste is digested out of capillary tubes.
In the case of the proteolytic and amylolytic ferments, the

1 Walther: Pawlow's Work ol the Digestive Glands, translated
by Thompson, London, 1902, p. 22.

Exp. o.

Exp. 6.

8.75

8 . 25

7.5

6.0

22.5

23.0

9.0

6.25

2.0

1.5

218

PHYSIOLOGY OF ALIMENTATION.

activity is expressed in number of centimeters of egg-albumin
or starch digested out of the tubes in the unit of time. As
has already been pointed out, this method is not free from

HOURS

24

1

2

3

4

5

1

2

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I

22

,

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20

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4

j

1

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/

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1

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8

/

\

\

/

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0

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1

Fig. 26. Curve of secretion of pancreatic juice after feeding 600 c.c.

milk. Two experiments.

(Copied from Pawlow: Work of the Digestive Glands. Trans, by

Thompson, London, 1902, p. 24.)

objection. The values obtained in different experiments
agree so well with each other; however, that the results must
be looked upon as correct, at least in the main.

Hourly Variation op Digestive Power of Pancreatic Juice
after a Meal of 600 c.c. Milk.

[our.

Lipolytic ferment.

Amylolytic

ferment.

Proteolyti

3 ferment.

Exp. a. Exp. 6.

Exp. a.

Exp. b.

Exp. a.

Exp. 6.

1

14.0 14.0

5.1

5.0

5.8

5.5

2

20.0 13.0

5.0

4.7

5.9

5.5

3

7.0 5.2

2.4

2.4

4.3

4.1

4

6.0 7.0

3.3

3.4

4.5

4.4

These values are expressed in curves in Fig. 27.

REGULATION OF THE PANCREATIC SECRETION. 219

The cause of these variations in the digestive power of the
pancreatic juice is not yet explained. A strong digestive

Hours

1

1

4

>

t (i (1

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o|4.0

£ 2.0

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Fig. 27. — Fermentative activity of hourly portions of pancreatic juice

after a meal ot 600 c.c. milk.

(Copied from Pawlow: Work of the Digestive Glands. Trans, by

Thompson London, 1902, p. 30.)

power may be found when much juice is being secreted by
the gland as well as when the flow is scanty. The variations

220

PHYSIOLOGY OF ALIMENTATION.

are probably associated with the progressive changes which
the food undergoes during digestion, but just how they are
connected is not yet known.

The variation, both in quality and quantity, which the pan-
creatic juice suffers when different diets are fed is indicated in
the following table. By strength of juice is meant the square
of the number of millimeters of egg-albumin or starch dis-
solved out of the capillary tubes, or the square of the num-
ber of cubic centimeters of standard barium-hydrate solution
used to neutralize the acid formed from the digested fat.
By the total quantity of ferment units is meant the product of
the strength of the juice multiplied by the quantity of the
juice in cubic centimeters. The amounts of food chosen
represent equivalents of nitrogen (Walther) .

Quan-
tity of
juice
in c.c.

Proteolytic
ferment.

Amylolytie
ferment.

Lipolytic
ferment.

Diet.

Strength

of

juice.

Total
quan-
tity ot
fer-
ment
units.

Strength

of

juice.

Total
quan-
tity
of fer-
ment
units.

Strength

of

juice.

Total
quan-
tity ot
fer-
ment
units.

Milk, 600 c.c. . .
Bread, 250 gms.
Meat, 100 gms..

48
151
144

22.6
13.1
10.6

1085
1978
1502

9
10.6
4.5

432
1601

648

90.3

5.3

25.0

4334

800

3600

In discussing the gastric secretion and its variations under
the influence of different diets, it was pointed out that not
only the quantity but also the digestive power of the juice
differs with different kinds of food. The above table shows
that for the pancreatic juice it is still more strikingly true
that each kind of food has its own particular kind of juice.
Each sort of food determines the secretion of a definite amount
of pancreatic juice. But still more remarkable is the variation
in the amount of the different ferments poured out upon the
foods. The juice poured out upon bread is exceedingly poor
in lipolytic ferment, while that poured out upon milk is very

REGULATION OF THE PAXCREAT1C SECRETION. 221

rich. The juice poured out upon meat occupies ;ui inter-
mediate position in this regard. The largest amylolytic
activity is found in the juice poured out on bread, less in the
juice poured out on milk, and still less in that poured out
upon meat. It is self-evident that so far as the fat- and starch-
splitting ferments are concerned the properties of the pan-
creatic juice correspond to the requirements of the food. A
diet rich in starch receives a juice rich in amylolytic fer-
ment, one rich in fat a juice containing much lipolytic fer-
ment. This is shown, as indicated in the above table, not
only by the strength of juice poured out upon these different
foods but also by the absolute quantities secreted by the
gland.

The behavior of the proteolytic ferment seems at first to
differ from that of the amylolytic and lipolytic. In dis-
cussing gastric secretion it was shown that the weakest juice
was poured out on milk. In the case of the pancreas, how-
ever, the strongest proteolytic juice is poured out upon this
food, while a weaker one is poured out upon bread and a still
weaker one upon meat. When, however, the quantity of
juice poured out upon these different foods is taken into con-
sideration we arrive at conclusions similar to those found to
hold for gastric secretion. As indicated in the above table,
when equivalent quantities of protein are fed in the form of
bread, meat, and milk, the total quantity of ferment units
poured out upon these foods stands as 1978:1502:1085. In
other words, vegetable protein demands from the pancreas,
as well as from the stomach, the largest number of ferment
units, while milk demands the least. The difference between
the secretion of the stomach and the pancreas is, therefore,
limited to the fact that the former pours out its ferment in a
very concentrated form upon bread, while the latter pours
it out in a more dilute solution.1

1 SccPawlow: Work of the Digestive Glands. Translated by Thomp-
son , London, 1902, p. 39.

222 PHYSIOLOGY OF ALIMENTATION.

3. The Relation of the Nervous System to Pancreatic
Secretion. — The secretion of juice by the pancreas is in-
fluenced by the vagus nerve in much the same way as the
secretion from the stomach. In this chapter of physiology
also, Pawlow and his coworkers have done most within recent
years to advance the state of our knowledge. The following
experiment shows unequivocally that the vagus nerve con-
tains fibres which influence the secretion of the pancreatic
juice. A dog in which a permanent pancreatic fistula has
been made after the fashion described above is employed. The
vagus nerve is divided in the neck on one side, the peripheral
end is laid bare, and after having a ligature passed around
it, is preserved under the skin. On the fourth day after
division the severed nerve is carefully pulled out of the
wound without hurting the dog in any way. No juice flows
from the pancreatic fistula. But one or two minutes after
the peripheral end of the vagus is stimulated by an induc-
tion current a drop of juice appears at the orifice of the
pancreatic duct, which is soon followed by another and
another in rapid succession. If the induction current is
interrupted the pancreatic juice continues to flow for four
or five minutes and then ceases. If now the stimulation be
renewed juice appears a second time, and so on.

The reason why the older observers never obtained a flow
of pancreatic juice when they stimulated the vagus is due to
the fact that in their experiments performed at one sitting
peripheral stimuli iuitiated by anaesthetic, pain due to opera-
tion, etc., acted upon the pancreas and produced a reflex
inhibition. That such sensory stimuli exert an inhibitory ef-
fect upon the pancreatic gland has been shown by Bernstein,
Pawlow, and others. Circulatory disturbances also inter-
fere with pancreatic activity. In the experiment described
above such peripheral stimuli are carefully avoided, first
by utilizing an animal which has recovered from the effects
of anaesthetic and operation, and secondly by stimulating
the vagus at a time when its cardiac fibres have degenerated

REGULATION OF THE PANCREATIC SECRETION. 22.1

to such an extent that stimulation no longer affects the
heart. At this time the fibres influencing the pancreatic
secretion are, however, still active.

But the influence of (lie vagus nerve can also be demon-
strated in an experiment performed at a single sitting. Special
precautions must be taken, however, to prevent the inhibition
of the gland either through nervous reflexes or through the
circulation. To do this a dog has his spinal cord divided
just below the medulla in order to shut out all peripheral
stimuli which might inhibit the activity of the pancreas.
After this has been done and artificial respiration started,
the thorax is opened and the vagus divided below the heart.
If now a cannula is inserted into the pancreatic duct a secre-
tion of pancreatic juice is noticed whenever the peripheral
end of the cut vagus is stimulated. By thus exciting the
vagus in the thorax its influence on the heart is avoided.

The experiments of Popielski x indicate that the vagus
nerve contains fibres which not only augment the secretion
of the pancreas but also such as inhibit it. If during the
acute experiment described above a solution of hydrochloric
acid is poured into the duodenum a vigorous secretion of
pancreatic juice is called forth which continues for a long
time. If now the vagus nerve be stimulated the secretion is
markedly diminished in amount, often stopped entirely.

The pancreas is influenced also by the sympathetic nerve,
as shown by the experiments of Kudrewetzky.2 This nerve
apparently carries two kinds of fibres to the gland — first,
vaso-constrictor, and secondly, such as influence the secretory
activity of this organ. If the sympathetic is stimulated in
the ordinary way by electric induction shocks a slighl in-
crease in secretion is observed, which lasts, however, only a
few seconds; then it ceases entirely even if the electrical
Stimulation is continued. This is due to the fact that the

1 Popiei.ski- c.ni rail. 1. f. Physiol., 1896, X, p. 105.

■ Kudrewetzky; Archiv t. (Anat. u.) Physiol., 1894, p. s::.

224 PHYSIOLOGY OF ALIMENTATION.

vasoconstrictor effects completely mask the secretory.
The two can be separated by mechanical stimulation of the
sympathetic. When this is done stimulation always leads
to an increased secretion from the gland, for, as is well known,
vaso-constrictor nerve fibres are not readily excited by
mechanical means. The two can also be separated by stim-
ulating the sympathetic several days after it has been divided.
The vaso-constrictor fibres are the first to degenerate, so that
only those influencing the secretory activity of the gland are
left to exhibit their characteristic effects.

4. The Normal Excitants of the Pancreas. — It has been
shown above that during a period of digestive inactivity the
pancreas secretes no juice; that after feeding, a large amount
of pancreatic juice is secreted. What determines this secre-
tion? The relation of the various inorganic constituents
of the food to the pancreatic flow has been studied by
Becker 1 and Dolinski.2

Acids of all kinds act as powerful excitants of the pan-
creatic secretion. If 250 c.c. of a 0.5 percent hydrochloric acid
solution, for example, are introduced by means of a catheter
into the stomach of a dog possessing a permanent pancreatic
fistula, the inactive pancreas begins to secrete within two or
three minutes. Within ten minutes the pancreatic flow
reaches its maximum and within the first hour some 80 c.c.
of juice may be collected. The rate of secretion steadily
falls, so that towards the end of the second hour only about
15 c.c. can be collected before the outflow ceases entirely.
If, instead of the hydrochloric acid solution, an equal amount
of water is injected into the stomach little or no pancreatic
juice is obtained, which shows that it is the acid which is
active. That at the end of such an experimental period the
pancreas is not exhausted can be readily proved by injecting

1 Becker: Archives des Sciences Biologiques, II, p. 433. Pawlow's
Work of the Digestive Glands. Translated by Thompson, London,
1902, p. 113.

2 Dolinski: Arch, des Sci. Biolog., Ill, p. 399.

REGULATION OF THE PANCREATIC SECRETION. 225

the hydrochloric acid a second time, when figures practically
the same as those given above can again be obtained. Phos-
phoric, citric, lactic, and acetic ackl behave in a way similar
to hydrochloric. Carbonic ackl also belongs in this group.

Sodium chloride in solution seems to be without effect
upon the pancreas, and alkaline solutions, such as calcium
hydroxide, sodium bicarbonate, and alkaline mineral waters,
have a distinctly inhibitory effect upon its secretion.

After what has been said it is not strange that gastric juice
acts as a chemical excitant of the pancreas, and to the same
degree as a hydrochloric acid solution of the same concentra-
tion. When the gastric juice of the acid food passing out
of the stomach is neutralized the effect of the latter in calling
forth a pancreatic secretion disappears. In what way the
acid is effective in acting upon the pancreas will be discussed
later when we speak of secretin.

In spite of the fact that starch is one of the constituents of
the food upon which the pancreatic juice acts, this carbohy-
drate, whether boiled or unboiled, and at any concentration,
affects the quantity of juice poured out by the pancreas no
more than an equal amount of water. A qualitative change
in its composition is, however, rendered probable by the ex-
periments of Walther, who found that a dog when fed on
bread secretes a pancreatic juice richer in amylolytic ferment
than when fed with meat.

Fat seems to be an excitant of the pancreas. Dolinski
and Damaskin l found that after introducing oil into the
stomachs of dogs a flow of pancreatic juice always ensued.

Do we have a psychic secretion of pancreatic juice similar
to the psychic secretion of gastric juice? This question can-
not yet be looked upon as definitely settled. Kuwschinski 2
showed in 1888 that tempting a hungry dog with Food led

1 Pawlow: Work of the Digestive Glands. Translated by Thompson,
London, 1902, p. 121.

; Kuwschinski: Paw 'low's Work of the Digestive Glands, Trans-
lated by Thompson, London, 1902, p. 121.

226 PHYSIOLOGY OF ALIMENTATION.

to a free secretion of pancreatic juice. This does not prove,
however, that the pancreas can be directly excited by this
means, for to tempt a hungry dog is to excite a gastric secre-
tion, and the acid flow produced in this way might readily be
the real excitant of the pancreatic flow. Two facts, however,
point strongly in favor of the existence of a psychic secretion
of pancreatic juice. First, tempting a dog with food or
sham feeding will cause a quiescent pancreas to become
active even when a gastric fistula allows the escape of the
gastric juice from the stomach as soon as formed ; secondly,
the latent period marking the beginning of secretion from the
stomach and the pancreas is different in the two cases. An
acid flow begins from the stomach five to ten minutes after
the beginning of sham feeding. The pancreas begins to
secrete after two to three minutes. If the acid and not a
true psychic element were responsible for the secretion of
pancreatic juice the pancreas should not become active until
after the gastric flow has commenced.

Water also acts as an excitant of the pancreas. When
150 c.c. of water are introduced unnoticed into the stomach
of a dog the pancreas begins to secrete, or augments its flow
two or three minutes after the water has entered the stomach.
If the experiment is properly performed this amount of water
does not excite a flow of gastric juice, so that a secretion of
pancreatic juice secondary to a secretion of gastric juice is
out of the question here.

Meat extracts, which were found above to be such good ex-
citants of the gastric glands, are no more effective in the case
of the pancreas than an equal amount of water.

What has been said in this section regarding the influence
of acids, food, etc., on the qualitative and quantitative com-
position of the pancreatic juice in the dog seems to hold
without modification for the human being. As evidence in
this direction we may cite the experiments of Glaessner1 on

1 Glaessner; Zeitschrift fur physiologische Chemie, 1904, XL, p. 46f

REGULATION OF THE PANCREATIC SECRETION. 227

his patient with a fistula of the pancreatic duel . ( Ilaessnek
fmmd thai the amount of juice secreted in the unit of time
was greatly increased soon after his patient took food.
Whereas under ordinary circumstances 10 to 15 c.c. (lowed
from the fistula per hour, 38 c.c. were obtained in the first
hour alter a meal, 34 c.c. in the second, and 46 c.c. in the
fourth. From this hour on the flow steadily decreased
until at the end of the eighth it had fallen to its original level.
It is evident, therefore, that the curve representing the rate
of secretion in the human being is similar to that which has
been described for dogs.

The amount of lipolytic, amylolytic, and proteolytic fer-
ment in the unit volume of pancreatic, juice Glaessner also
found to vary with the taking of food. Between meals this
was least, while the slow rise which began during the first
or second hour after eating was found to attain its maximum
about the fourth, when it fell once more in the following four
1 lours to its original level. The alkalinity of the juice was
also found to increase after the taking of food. While with
phenolphthalein as indicator 1 c.c. of decinormal acid was re-
quired to neutralize 10 c.c. of pancreatic juice between meals,
it required 5 c.c. of the acid to neutralize the same amount of
juice obtained during the fourth hour after a meal.

The presence of an acid in the duodenum seems to increase
the pancreatic flow in a human being just as in a dog.
Glaessner found that the introduction of several hundred
cubic centimeters of a weak hydrochloric acid into the
stomach of his patient was followed almost immediately by an
increased pancreatic flow which attained its maximum by the
end of the first hour, and fell to the original level once more
by the end of the second, as in the case of the dog.

5. Pancreatic Secretin. — In discussing the effect of acids
upon the pancreal ic flow, do mention was made of the mechan-
ism by which this most powerful excitant of the gland accom-
plishes its results. Pawlow believed that the gland was
excited through a nervous reflex, initiated by the effect of

228 PHYSIOLOGY OF ALIMENTATION.

the acid upon the mucous membrane of the duodenum.
That this explanation is incorrect is indicated by the experi-
ments of Popielski, Wertheimer, and Lepage, who found
that the introduction of acid solutions into the stomach or duo-
denum still excited the gland to secretion, when all the nerves
supplying the pancreas and duodenum had been cut. These
authors, nevertheless, clung to the idea of a nervous excita-
tion of the gland, at least in part. What had been rendered
probable through the experiments of Popielski, Wertheimer,
and Lepage was made still more evident by the researches
of Bayliss and Starling, who found that it is possible to
isolate the pancreas from the duodenum, to divide all the
nerves going to a loop of the small intestine, and nevertheless
get a copious pancreatic secretion soon after an acid is injected
into this loop.

How, then, does the acid act? The experiments of Bay-
liss and Starling * have shown that the connection between
intestine and pancreas is really only a chemical one. The
introduction of an acid into the duodenum or upper part
of the small intestine brings about the production of a chemi-
cal substance in the mucous membrane which is called secretin.
Since there are other secretins, it is well to call the one under
consideration here pancreatic secretin. As the pancreatic
secretin is formed it is rapidly absorbed into the blood, with
which it travels to the pancreas, and excites this organ to
secretory activity.

Pancreatic secretin may be obtained from the upper part
of the intestine of any of the vertebrates. It is best pre-
pared by scraping off the mucous membrane of the upper
two feet of the small intestine, treating this in a mortar with
sand and 0.4 percent hydrochloric acid, and then boiling the
mixture. After neutralization with caustic soda the whole
is filtered. The clear liquid which passes through the filter
contains the secretin. In order to obtain the secretin in a

1 Bayliss and Starling: Proceedings of the Royal Society, 1904,
LXXIV,p.310; Starling: Lancet, 1905, CLX1X, pp. 339, 423, 501,

REGULATION OF THE PANCREATIC SECRET ION 229

still purer state, the filtrate may be treated with absolute
alcohol and ether, which precipitates certain impurities but
allows the secretin to remain in solution. Secretin is there-
fore a substance which is unaltered by boiling and is soluble
in alcohol. It can moreover be shown that it is diffusible.
It is not necessary that the mucous membra.ne from which
the pancreatic secretin is to be obtained should be living.
It can be obtained just as well from an intestine which has
been killed by boiling. Pancreatic secretin has, therefore,
none of the ordinary characteristics of a ferment, and recent
experiments seem to indicate that it belongs to the class of
the peptones. It is possible, therefore, that secretin repre-
sents nothing but a product of proteolytic activity.

A few cubic centimeters of the secretin-containing filtrate
obtained as described above when injected into the veins of
an animal call forth a plentiful secretion of clear pancreatic
juice, which may be collected by means of a cannula placed
in the pancreatic duct. The pancreatic secretin obtained
from one animal is not specific for that class alone, but will
when injected into the veins of any other vertebrate call
forth a copious pancreatic flow. It is wrell to add that the
pancreatic juice obtained after the injection of secretin is to
all appearances identical with that obtained after an ordinary
meal.

Bayliss and Starling's findings alter somewhat our con-
ception of the events which follow each other in the intestinal
canal. A consideration of the facts which have been out-
lined above makes us imagine the changes which occur here
to be somewhat as follows: The acid gastric contents enter
the duodenum and bring about the formation of pancreatic
secretin. This is absorbed into the circulation and, passing
with the blood-current through the pancreas, causes a secre-
tion of pancreatic juice. Since the pancreatic juice is able to
neutralize free acids, it will decrease little by little the acidity
of the gastric contents which have come into the duodenum.
Little by little also will the rate of production of secretin be

230 PHYSIOLOGY OF ALIMENTATION.

decreased. But not until all the acid in the duodenum has
been neutralized will the production of pancreatic secretin,
and, in consequence, the pancreatic flow, cease entirely.

This chemical interaction between the stomach, duodenum,
and pancreas is further aided by the rhythmic opening and
closing of the pyloric sphincter, which has already been de-
scribed.1 The presence of free hydrochloric acid in the
stomach causes the pyloric sphincter to relax and some of
the gastric contents to pass into the duodenum. As soon
as the acid reaches this part of the intestinal canal, however,
the sphincter is closed reflexly, and remains closed until the
duodenal contents have become neutralized by being mixed
with pancreatic juice. As soon as this neutralization has
been accomplished, the pylorus relaxes a second time and a
fresh portion of the gastric contents enters the duodenum.
This in its turn calls forth a production of pancreatic secretin,
a secretion of pancreatic juice, and the cycle is repeated.

6. Significance of the Physiology of the Gastric and Pan-
creatic Secretions. — The advances made in our knowledge of
gastric and pancreatic activity have done much to give us an
experimental basis for what has hitherto been empirical in
medical practice and have at the same time pointed out the
direction which medicine must take in combating certain
affections of the alimentary tract. The experimental results
detailed above show most clearly the physiological impor-
tance of the appetite. Appetite is synonymous with a copious
secretion of gastric juice, and the necessity of this secretion
for a proper and rapid digestion of proteins and the evil
effect of its absence are manifest nowhere more clearly than
in those disorders which are associated with a deficient secre-
tion from the stomach. We recognize, in consequence, the
importance of catering to the appetite in health, in order to
maintain gastric digestion at its best, and the urgency of
restoring this physiological sense in those diseases in which

1 See p. 16.

REGULATIOX OF THE PANCREATIC SECRETION. 231

it is absent. As the pancreatic secretion is probably in-
fluenced by appetite in the same way as the- stomachy v. •
an additional reason for recognizing its medical importance.
The influence of the appetite upon the secretion of the gastric
juice contributes also to our understanding of the beneficent
effects which follow the feeding of a patient with a "weak"
stomach at frequent intervals and only small amounts at a
time. Under these circumstances the appetite juice, rich in
ferments, recurs several times and digestion is furthered in
consequence.

We are also in a position to understand now the good effects
of condiments and bitters. Pharmacologists have looked in
vain for a direct secretory effect of these substances upon
the stomach and pancreas, Every-day observation, however,
seems to support indisputably the fact that these substances
increase the appetite. If this be true, we have arrived at an
explanation of the good effects following their moderate use,
for to increase appetite is to increase gastric and pancreatic
secretion.1 We can recognize also the relation which appetite
and gastric secretion bear to each other. Quite contrary
to the generally accepted idea that the presence of gastric
juice in the stomach is the cause of appetite, we must say that
gastric secretion is its consequence.

It is necessary to revise our ideas of the usefulness of meat
soups, meat extracts, meat juices, etc. Few medical men to-
day are not acquainted with the valuelessness of the first two
from a nutritive standpoint. But since they excite a secre-
tion of gastric juice, even in the absence of appetite, they are
eminently useful, for they can in this way be employed to
bring about the digestion of food which is introduced into
the stomach subsequently. Because of this fact soups ful-
fil a good function when employed at an ordinary meal, for
they help to maintain a secretion of digestive juice which has
been inaugurated by the appetite.

1 SeePAWLOw: Work of the Digestive Glands. Translate! 1 by Thomp-
son, London, 1902, p. 13S et scq.

232 PHYSIOLOGY OF ALIMENTATION.

Milk and water are also independent excitants of the gastric
secretion,. We find in this another reason for the use of water
with meals. Milk has from the earliest times been considered
an easily digested food for children and invalids. Not only
does this fluid cause a secretion of gastric juice, but, as has
been shown above, a weaker gastric juice and a smaller
quantity of pancreatic juice are poured out on milk than on
an equivalent amount of nitrogen contained in any other
food. The work performed by these digestive glands is
therefore less, and the saving of energy, in consequence, is
greater than when meat or bread, for example, is fed. The
amount of work which the organism does in order to assimi-
late a certain amount of nutriment must always be sub-
tracted from the energy value of the food itself. This is not
ordinarily considered in determining the value of various
foods. We have seen above, however, that equivalent
weights of nitrogen in the proteins of meat, bread, and
milk cost the organism different amounts of glandulai
energy.

Fat inhibits the secretion of gastric juice. We find in this
the explanation of the fact that its presence in a mixed meal
impedes the rate of digestion, and hence is contraindicated in
cases of feeble digestion, while it works excellently in cases
of hyperacidity and hypersecretion. The alkalies and alka-
line salts belong in this group of substances which inhibit the
secretions of the gastric mucosa and the pancreas.

We have learned from experiments detailed above the
uselessness of mechanical stimulation of the gastric mucosa
in bringing about a secretion of gastric juice. Neither
mechanical stimulation through coarse food or by means
of special apparatus, such as an inflatable balloon, can there-
fore be looked upon as rational treatment for those gastric
disorders which are characterized by deficient secretion of
juice. Care must be taken not to confound this statement
with the relation between mechanical stimulation and the
motor functions of the stomach.

REGULATION OF THE PAXCREATIC SECRETION. 233

A defective secretion of gastric juice, be its cause what it
may, is of medical importance from other points of view
than that it interferes with the proper digestion of proteins.
A lack of hydrochloric acid in the stomach allows the develop-
ment here of a large number and variety of bacteria which
in its presence is impossible. The development of these
bacteria is associated with fermentative changes in the
stomach contents, which assume clinical importance in pro-
portion to their character and amount. Lack of free hydro-
chloric acid in the stomach delays the opening of the pyloric
sphincter, which leads to retention of the food in the stomach
for longer periods of time than normally. In this way also
bacterial fermentation is allowed to become more effective.

When ultimately the stomach contents pass into the small
intestine, they flood this portion of the alimentary tract with
bacteria and, as already pointed out, the bactericidal activity
of the small intestine is by no means limitless. The fermenta-
tive changes in the food initiated in the stomach may in con-
sequence continue in the intestine, with effects upon the
organism as a whole (due in part to absorption of the bacterial
products formed, in part to a lack of properly digested foods)
which are sometimes unimportant, sometimes serious.

A deficient amount of gastric juice leads to yet other dis-
turbances in the organism. We are slowly beginning to
recognize the intimate connection which exists between
different organs in the body and how the proper behavior
of one is dependent upon that of another. This relation
between organs exists also between different portions of the
alimentary tract. It might be thought at first that from
the standpoint of digestion alone a deficient amount of gastric
juice is without consequence, for the pancreas contains a
proteolytic ferment which is able to split proteins even more
readily than the acid-protoinase of the stomach. Matters
are not so simple, however. It was seen above that the
presence of acids in the duodenum brings about a secretion
of pancreatic juice. If now the gastric secretion is de-

234 PHYSIOLOGY OF ALIMENTATION.

ficient, it means a lack of acid in the duodenum, and this
in turn means a deficient secretion of pancreatic juice.

7. On the " Adaptation " of the Digestive Glands to the
Character of the Food. — The opinion that the secretions
of the various digestive glands "adapt" themselves to the
character of the food consumed by the individual, that, in
other words, each diet calls forth a particular kind of diges-
tive secretion, has been expressed from time to time by various
authors. With all of them, however, this opinion has rested
more upon philosophical speculations than upon experimental
facts.

The first to attempt to give experimental foundation to such
an idea was Pawlow, and with him Chigin and Walther.
But the experiments which these investigators have detailed
in support of their belief, and which have been touched upon
in the preceding pages, have been so energetically attacked
by others that, at the best, they can be looked upon as by
no means convincing.

With all the more pleasure, therefore, can we proceed to a
discussion of the experiments of Weinland,1 which indicate
without question that one digestive gland at least, the pan-
creas, can and does "adapt" itself to a particular diet.
Weinland 's experiments show that the pancreas and pre-
sumably, therefore, the pancreatic juice of the adult dog,
which normally contain little or no lactase, come to con-
tain this enzyme in large amounts if the dog is fed milk-
sugar, or a diet containing milk-sugar, such as milk. This
means that the pancreas and pancreatic juice, which in the
adult dog normally contain little or no ferment which can act
upon lactose and split this into .galactose and dextrose, de-
velop this sugar-splitting ferment in response to certain diets.

What has been said can be best illustrated by introducing
one of Weinland 's experiments. An adult dog was kept on
an abundant diet, but free from milk-sugar, for five days;

1 Weinland: Zeitschr. f. Biol., 1899, XXXVIII, p. 16; ibid., 1899,
XXXVIII, p. 607; ibid., 1900, XL, p„ 386.

REGULATION OF THE PANCREATIC SECRETION. 235

he was killed and the pancreas removed immediately, an
extract made of it and its power of acting upon milk-sugar
(lactase content) determined. The extracl was found to
have practically no effect upon milk-sugar, indicating, there-
fore, (hal it contained little or no ferment capable oi acting
on lactose. A second, also advli dog received for 15 days a
diet similar to that given the first dog, only :!() gms. of milk-
sugar were added to the daily food ration. When at the
end of this time the dog was killed, the pancreas removed
and treated as that of the first dog, it was found that the
'pancreatic extract split milk-sugar most energetically into galac-
tose and dextrose, 43 percent of the added lactose being
split within twenty-four hours. It is self-evident, therefore,
that under the influence of milk-sugar feeding the pancreas
can develop a ferment (lactase) which has the power of split-
ting milk-sugar and which is entirely absent (or present in
only very small amounts) in the pancreas of an adult dog
not so fed.

The percent of sugar split as given above is by no means
the highest that Weinland ever attained. In three other
experiments in which the dogs were fed ordinary milk instead
of pure milk-sugar, the pancreatic extracts were able to split
respectively 54 percent, 73 percent, and 75 percent of the
lactose added to them. When it is pointed out that the
pancreas obtained from dogs of a corresponding age, but not
fed on milk-sugar, possess practically no milk-sugar-splitting
activity it is self -apparent how striking is this "adaptation''
of the pancreas to the character of the diel .

It is of physiological interest that the quantitative variation
in the amount of lactase found not only in the pancreas but
also in the small intestine is intimately connected with the
age of the individual, or, as we can say now, with those
periods of life in which milk-sugar furnishes a pari of the
food consumed by the animal. Apparently all sucklings
(including Hie new-born child) have lactase present in the
pancreatic juice and the intestinal juice. This has been

236 PHYSIOLOGY OF ALIMENTATION.

proven true for all mammals examined. In adult life,
however, the lactase of the pancreas disappears very largely,
at times entirely, and the lactase of the intestinal mucosa and
its secretion decreases much in amount (and in some animals
disappears entirely) unless milk-sugar continues to serve as
an article of food for the adult animal.

We have yet to discuss the mechanism of this adaptation.
A direct effect of the milk-sugar upon the pancreas from the
lumen of the intestine is practically impossible, for the pan-
creas is connected with the gut by only a slender excretory
duct, through which, moreover, during the periods of diges-
tion an uninterrupted stream of juice pours. It might be
thought that when an excessive amount of milk-sugar is fed,
some passes over into the circulation, for we can discover
milk-sugar in the urine; and this absorbed sugar might be
thought to act directly upon the pancreas. That this idea
is not correct follows from the fact that the intravenous
or subcutaneous injection of milk-sugar is not followed by
the appearance in the pancreas of an increased amount of
lactase. Neither does a subcutaneous or intravenous injec-
tion of one of the products of milk-sugar digestion, such as
galactose, accomplish this result. In order that this may
occur the milk-sugar must come in contact with the mucosa of
the intestine.

We are indebted to Vernon 1 for a further analysis of the
problem. This author, who entirely confirms the experimental
findings of Weinland, has shown that through contact of the
milk-sugar with the intestinal mucosa a substance is produced
which is absorbed into the blood and which when it is carried
to the pancreas brings about in this organ an increased pro-
duction of lactase. This phenomenon belongs, therefore, in
the same group with those which we discussed under the
heading of the secretins.2 We have here another example of
the chemical connection which exists between different organs.

1 Vernon: Journal of Physiology, 1905. 2 See pp. 211 and 227.

CHAPTER XIII.

THE REGULATION OF THE BILIARY AND INTESTINAL
SECRETIONS— THE FUNCTIONS OF THE BILE.

i. The Secretion of Bile. — In discussing the question of
the secretion of bile we must distinguish between the forma-
tion of the bile in the liver, together with its collection in
the gall-bladder, and the flow of the bile into the intestinal
canal. The two processes go on independently of each other,
and the older experiments made by producing a fistula of the
gall-bladder give us an insight only into the first of these
questions. What determines the flow of bile into the intestinal
canal?

This question has recently been investigated by Bruno and
Kladnizki,1 who have .succeeded in turning the orifice of the
gall-duct outwards in such a way that the bile flows out
upon the skin. This they accomplish by cutting out of the
intestine the orifice of the duct with its surrounding mucous
membrane and suturing the latter to the serous coat of the
duodenum. The entire loop of intestine is then sewed into
the abdominal wound.

Contrary to the older observations made on gall-bladder
fistula? it has been found that the bile does not flow into the
intestine all the time. The secretion of bile is intimately
connected with taking food and does not begin until a definite
time has elapsed after partaking of a meal. The length
of this latent period differs with the different kinds of food.
The secretion continues as long as the period of digestion,

1 Buuno and Kladnizki: Pawlow's Work of (he Digestive Cdands.
Translated by Thompson. London, 1902, p. 155. Bruno: Review
in Jahresber. d. Thierchemic XXVII, p. 111.

237

238 PHYSIOLOGY OF ALIMENTATION.

but not at an even rate, fluctuating in quantity with varia-
tions in the nature of the food.

When different food substances are fed separately to a dog
operated upon as indicated above, it is found that neither
water, acids, raw white of egg, nor boiled starch as a thick or
a thin paste causes a flow of bile. Fat, however, and to a
less extent extractives of meat, and the digestion products
of white of egg set up a free discharge of the secretion. The
bile, therefore, is not unlike the gastric or pancreatic juice,
which has each its specific excitants.

How now do the various substances which bring about a
secretion of bile into the intestine do this? The explana-
tion which has been and is given ordinarily is that the bile
flows in consequence of a nervous reflex which is initiated
through the action of certain constituents of the intestinal
contents upon the mucous membrane of the duodenum. It
is much more probable, however, that the connection between
duodenum and liver is of a chemical character. This is shown
by the experiments of Bayliss and Starling, who find that
pancreatic secretin not only augments the flow of pancreatic
juice but also the discharge of bile into the intestine. It is
an interesting fact that the pancreas and liver should have
such a common excitant, for as will be shown immediately
the bile augments in a most marked way the digestive prop-
erties of the pancreatic juice.

2. The physiological importance of the bile is shown very
clearly in the classical observation of Claude Bernard and
the more modern one of Dastre.1 Claude Bernard noticed
that in rabbits, in which the opening of the pancreatic duct
into the intestine lies some 30 cm. below that of the bile-
duct, the absorption of fat after a fatty meal does not begin
until the food has passed the pancreatic duct, for while the
lymph leaving the intestine below this point is milky in ap-
pearance that above it is clear. This shows that the bile

1 Dastre: Arch, de pliys. norm, et path., 1890, XXII, p. 315.

BILIARY AND INTESTINAL SECRETIONS. 239

alone is unable to bring about an absorption of fat. Dastre's

experiments consisted in producing artificially in dogs the
reverse of the above conditions. After ligating the bile-dud
he established a fistulous opening between the gall-bladder
and the middle of the small intestine. In spite of the fact
that the pancreatic juice entered the duodenum as usual,
no fat was absorbed from the entire upper half of the small
intestine. Not until the biliary fistula was passed did the
lacteals show a milky appearance to indicate fat absorption.
This shows how important is the function of the bile for the
rapid and proper absorption of fats, and indicates clearly
that physiological ends are best served when pancreatic juice
and bile act together upon fat.

The important role of the bile in the digestion of fats can
also be shown very clearry in experiments carried out in glass.
Heidenhain, Williams, and Martin have all shown that the
presence of bile in a reaction mixture of fat and pancreatic
lipase markedly increases the velocity of the formation of
fatty acid and alcohol. Especially commendable are the
recent experiments of Rachford, Bruno, and Glaessner,
carried out with purified ferments instead of ordinary extracts
of the pancreas, or the pure pancreatic and biliary secretions
themselves. Glaessner's * results are given in the following
table and deal with human pancreatic juice. It is interesting
to note that what Schepowalnikow observed in dogs is true
here also, namely, the simultaneous presence of both bile
and intestinal juice favors the lipolytic activity of the pan-
creatic juice more than that of either one by itself. The
last column indicates the percent of fatty acid formed in
twenty-four hours.

Fatty
acid.

100 c.c. olive-oil + 20 c.c. pancreatic juice =_'_",

100 c.c. olive-oil + 20 c.c. pancreatic juice + 10 c.c. bile =30%

100 c.c. olive-oil + 20 c.c. pancreatic juice+ 10 c.c. intestinal juice 35' ,
100 c.c. olive-oil + 20 c.c. pancreal ic juice+ L0 c.c. bile : 10 c.c. in-
testinal juice = in1,

1 Glaessner: Zeitschr. I. physiol. Chem., XL, p. 170.

240 PHYSIOLOGY OF ALIMENTATION.

A long-accepted explanation of the role of bile in hastening
fat digestion has been sought in its power of favoring the
emulsification of fats. Through emulsification of the fat the
amount of surface exposed to the action of lipase is greatly
increased. Experiments carried out by Hewlett x indicate
that bile acts in yet another and even more direct way than
this in favoring the activity of the ferment. These experi-
ments show at the same time which constituent of the bile
it is that favors the fat-splitting activity of the pancreatic
juice, for bile is a mixture of a number of chemical entities.

If, instead of the ordinary very sparingly soluble fats, the
soluble triacetin is used, so that the question of emulsification
plays no part whatsoever, it is found that bile still markedly
hastens the action of pancreatic juice upon this substance.
In one experiment, for example, pure pancreatic juice ob-
tained from a dog by secretin and atropin injections pro-
duced in one hour at 20° C. enough acid to require 0.5 c.c.
1/20 normal alkali solution to neutralize it, and in twenty-
four hours 12.6 c.c. In another tube which contained the
same amount of pancreatic juice and triacetin, but in addi-
tion a small amount of bile, the acidity produced in one hour
amounted to 13.0 c.c, in twenty-four hours to 18.6 c.c. of
a 1/20 normal alkali solution. That the acceleration of the
decomposition in the later hours of the experiment should
be less than in the earlier is readily explained by the fact
that the reaction is approaching an equilibrium.

If now an attempt is made to discover which constituent
of the bile it is that favors in this way the decomposition of
triacetin under the influence of pancreatic juice, it is found,
first of all, that boiling the bile does not destroy this property.
It is therefore probable that we are not dealing with the
action of any enzyme contained in the bile. Hewlett has
further shown that this property resides neither in the choles-
terin nor in the bile pigments, nor in variations in the reac-

1 Hewlett: Johns Hopkins Hospital Bulletin, 1905, XVI, p. 20.

BILIARY AND INTESTINAL SECRETIONS. 241

tion or in the amount of calcium salts present. All the
accelerating effects of bile upon the lipolytic activity of
pancreatic juice can be equally well produced by (lie ad-
dition of lecithin. This is shown very well in the follow-
ing table, in which is indicated the number of cubic cen-
timeters of a 1/20 normal alkali solution which were required
to neutralize the acid formed in twenty-four hours in three
tubes containing the same amounts of pancreatic juice and
triacetin.

Pancreatic juice + triacetin = 4.3 c.c.

Pancreatic juice + triacetin + 2 c.c. bile =19.5 c.c.

Pancreatic juice + triacetin + 2 drops alcoholic solution of

lecithin = 19 . 9 c.c.

Commercial bile salts also accelerate the action of pan-
creatic juice on triacetin, but when these salts are purified
they lose this power, which seems to indicate that the action
of the crude preparation is determined solely by its con-
tamination with lecithin.

As to the manner in which the bile assists the lipolytic
action of the pancreatic juice, we have as yet no satisfactory
explanation.

Bile also favors the action of some of the other ferments
contained in the pancreatic juice. But while bile may even
treble the velocity with which fats are digested, it only doubles
the velocity with which amylase will act on starch, or alkali-
proteinase (trypsin) on proteins.

Aside from its action as an aid to the pancreatic ferments,
bile has yet other, though perhaps scarcely as important,
functions. While a large number of the fatty acids are freely
soluble in water, this is not true of the fatty acids derived
from most of the fats (stearin, palmitin, olein) which consti-
tute our food. Moore, Rockwood, and Pfluger's 1 studies

1 Moore and Rockwood: Journal of Physiology, 1897, XXI, p. 58.
Tfluueh's numerous papers on fat are contained in Pfluger's Archiv,
Vols. LXXX to LXXXVI (1900 to 1901).

242 PHYSIOLOGY OF ALIMENTATION.

are therefore of great importance, which show that a mix-
ture of bile and sodium carbonate is able to dissolve large
amounts of stearic and palmitic acids. Bile is able to keep
even the insoluble calcium and magnesium soaps in solution.

The presence of bile in a reaction mixture of protein and
gastric juice retards the action of the ferment greatly. It
seems plausible, therefore, that the bile is of physiological
importance by interfering with the activity of the gastric
juice after this escapes into the duodenum from the
stomach.

To the bile has also been attributed an antiseptic action,
and it has been believed that through its presence the de-
velopment of bacteria throughout the alimentary tract is
markedly inhibited. Careful study seems to indicate, how-
ever, that this antiseptic action is only very weak, if it is pres-
ent at all. Bacteria develop freely in bile itself and culture
media containing bile. The increased putrefaction of the
alimentary contents, which is observed in at least some cases
of icterus, must therefore be attributed to other causes.
Foremost among these must stand the less perfect absorption
of the foodstuffs whose presence in the alimentary tract
furnishes a ready culture ground for the various bacteria
found here.

The bile is believed to aid intestinal peristalsis. This
idea seems borne out by clinical observation, though labora-
tory experiments in this direction have brought no unequivo-
cal results. If it is true that a lack of bile leads to a de-
creased peristalsis, we could readily find in the retention of
alimentary contents from this cause an additional reason for
the increased intestinal putrefaction found in these cases.

We must,' in conclusion, call attention to a function of the
bile which is still questioned by some authors. According
to some recent experiments, it is claimed that lipase is secreted
in the pancreatic juice only in an inactive form, that is, as a
proferment or zymogen, and that this inactive form is acti-
vated through the bile. The bile would therefore serve the

BILIARY AND INTESTINAL SECRETIONS. 243

same importanl function in fat digestion thai the intestinal
juice serves through the enterokinase it contains in protein
digesl ion.

3. Regulation of the Intestinal Secretion. — In order to
obtain a collection of pure intestinal juice use is made of
Thiry's classical fistula., or Thiry's fistula as modified by
Vella. An opening is made in the abdominal wall of an
animal, and a suitable loop of intestine is pulled out. Two
transverse cuts separate any desired length of the intestine
from the main portion of the tube, the continuity of which is
restored by an end-to-end anastomosis. The separated
loop of intestine is then closed at one end by a purse-string
suture, while the opposite end is sewed into the edges of the
wound. In this way a test-tube shaped piece of the bowel
is separated from the main body of the gut (Thiry fistula),
or both ends may be sewed into the abdominal wound when
we have the so-called Thiry-Vella fistula. The artificial
production of all the most successful fistula? along the gastro-
intestinal tract is modelled after the original Thiry operation
on the small intestine.

In the quiescent state of the animal practically no secre-
tion can be obtained from such an isolated loop of intestine.
As soon as food, such as starch paste, sugar, or peptone, is
introduced into the loop an increased secretion takes place.
Apparently, therefore, intestinal juice is secreted under
ordinary circumstances only by those portions of the gut
with which food is in contact, and not throughout its entire
length. The presence of food may cause a secretion either
through ils mechanical or chemical properties. That mere
mechanical stimulation may be effective in causing a secre-
tion of intestinal juice is proved by the fact that the irritation
of a cannula in an intestinal fistula, a rubber ball, etc., all
lead to a secretion of juice. According to Pawlow and his
coworkers the intestinal juice obtained in consequence of
mechanical stimulation alone differs from that obtained by
chemical means. The former kind consists chiefly of water

244 PHYSIOLOGY OF ALIMENTATION.

and salts with but very little or no enter okinase.1 When the
secretion is poured out upon food the intestinal juice is rich
in enterokinase. Apparently much more powerful than the
food itself in bringing about an intestinal secretion are the
pancreatic ferments which, under ordinary circumstances,
accompany the food along the intestine. An isolated loop
which is secreting little or no juice will become active very
soon after a few cubic centimeters of pancreatic juice are
put into it. If the pancreatic juice is previously boiled, this
property is lost. Which of the pancreatic ferments is active
in this direction is not yet known.

Observers agree that the normal enteric juice is a thin,
slightly yellowish liquid, ordinarily said to be alkaline in
reaction. The fluid which collects in the course of a few
weeks in loops of intestine which are ligatured off from the
main tube probably does not represent a normal secretion.
Usually this is more or less gelatinous and represents no
doubt the inspissated intestinal juice plus the mucin and
other abnormal substances poured out by the loop in conse-
quence of the "catarrh" which arises in it.

The nervous system no doubt influences the secretion
from the small intestine, but in just what way is not known.
The statements made by different observers contradict each
other in many points. A secretion of fluid occurs into the
intestine when all the nerves passing to the loop have been
severed. This so-called "paralytic secretion" contains, ac-
cording to Mendel's observations, all the ferments present in
the normal juice. A secretion of fluid into isolated loops of
intestine when entirely removed from the body also occurs.
All the structures necessary for secretion must therefore be
contained in the wall of the gut, and it would no doubt be
straining a point should we attribute this secretion to the
nervous plexuses found in the wall of the intestine, and not
solely to the mucous membrane. The fluid secreted into
loops entirely removed from the body is not to be regarded

1 See p. 240.

BILIARY A.XD INTESTINAL SECRETIONS. 245

as normal intestinal juice. For this we need the cooperation
of the circulating blood, from which are taken the substances
which cither directly or after they have been changed into
new chemical compounds through the activities of the mucous
membrane go to make up the intestinal juice.

Stimulation of the vagus nerve in the neck or below the
diaphragm seems not to affect the secretion of enteric
juice. Removal of the cceliac or mesenteric plexuses seems
to bring about an increased secretion similar, perhaps, to
the ordinary paralytic secretion but not so great in amount.
If certain of the ganglia are left behind, the secretion may
not take place.

Attention has already been called to the fact that the
intestinal juice has not the same chemical composition through-
out its entire length. Special mention must be made of the
secretion of the duodenum. In addition to the glands of
Lieberkuhn found throughout the whole of the small intes-
tine the duodenum contains the glands of Brunner. His-
tologically these resemble the glands of the stomach. The
debate which has long been carried on as to whether the
proteolytic ferment found in the duodenal juice is acid- or
alkali-proteinase, or amphoproteinase can be looked upon as
decided through Abderhalden's work. While it is impossible
under certain circumstances to say whether we are dealing
with pepsin or trypsin when a fluid containing one or both
of them is allowed to act on fibrin or any other complex pro-
tein, it is possible to do this when polypeptides are used. Al-
kali-proteinase will split certain polypeptides not affected by
acid-proteinase and vice versa. In this way it has been possi-
ble to prove that the proteolytic powers of the duodenal juice
are due to acid-proteinase (pepsin) secreted by the glands of
Brunner. As is universally the case, the proteolytic fer-
ment of the duodenal juice is also accompanied by a milk-
curdling ferment. As a whole, therefore, the duodenal juice
is very like gastric juice, yet the physiological importance
cf (he latter when compared with the former is not great.

246 PHYSIOLOGY OF ALIMENTATION.

The secretion of the large intestine is small in amount and
rich in mucin. It is stated to be alkaline in reaction, and to
contain no ferments in sufficient amount to be of physiologi-
cal importance. The large intestine acts chiefly as an organ
of absorption.

4. Enterokinase. — This is the term given by Pawlow to a
substance discovered by Schepowalnikow in the mucous
membrane of the small intestine which has the interesting
property of inaugurating or at least of increasing enormously
the proteolytic power of the pancreatic juice as it flows from
the gland.

We are probably correct in believing that neither the pan-
creas nor the pancreatic juice obtained directly from the
pancreatic duct contains any alkali-pro teinase (trypsin), but
only a substance (the so-called proferment or zymogen) which
can be converted into this ferment through contact with
enterokinase. Under physiological conditions this contact
with enterokinase is established as soon as the pancreatic
juice flows over the mucous membrane of the small intestine,
the walls and secretions of which contain this activating sub-
stance. The amount of mucous membrane necessary to
bring about at least some activation of the otherwise inactive
pancreatic juice is very small according to Delezenne and
Frouin's 1 experiments. In the ordinary method of making
a pancreatic fistula according to the method of Heidenhain
and Pawlow,2 by cutting out a small portion of the mucous
membrane surrounding the pancreatic duct and sewing this
into the edge of the abdominal wound, the escape of the pan-
creatic secretion over this bit of mucous membrane is sufficient
to give it well-marked digestive properties for proteins. If
the escape of the juice across the transplanted mucous mem-
brane is avoided by inserting a cannula into the duct above

1 Delezenne and Frotjin: Compt. rend, de Soc. biol., 1902
CXXXIV, p. 1524.

2 See p. 215.

BILIARY AND INTESTINAL SECRETIONS. 247

it , juice cut irely incapable of digesting egg albumin is obtained.

This juice readily becomes active in this direction if a .small
amount (a drop or two) of intestinal juice obtained from
an intestinal fistula in another animal is added to it.

As to the nature of enterokinase but little is known at
present, for the substance cannot be obtained in even an
approximately pure state. Since it is readily destroyed at
comparatively low temperatures Pawlow has looked upon it
as a ferment. This conception of enterokinase scarcely har-
monizes with the observations that have been made, which
indicate that a definite amount of enterokinase-containing
fluid can activate only a limited amount of pancreatic juice.
True ferments, it is well-known, act upon an infinite amount
of substance if only sufficient time is given.

The secretion of enterokinase is not to be looked upon as
a function performed by the small intestine at all times.
Enterokinase appears and disappears from the juice poured
out by the upper portions of the small intestine in the same
way as the amount of bile poured into the duodenum is con-
trolled by such circumstances at the taking of food. In fact,
the secretion of enterokinase is connected with physiological
processes going on in the intestine in the same way as the
secretion of bile. When the small intestine is stimulated
mechanically it secretes a juice, but it is thin and watery and
contains practically no enterokinase. As soon, however, as
a few cubic centimeters of pancreatic juice are introduced
into the lumen of the intestine, the juice secreted becomes
rich in enterokinase. Boiled pancreatic juice does not have
this power. The secretion of the watery constituents and
of the enterokinase of the intestinal juice represent, there-
fore, different physiological processes.

The idea that pancreatic juice obtained directly from the
pancreatic duct has no power to digest proteins contradicts
the views of a number of observers who have claimed that
the spleen furnishes at the height of digestion a substance
which is absorbed into the blood and through its action on

248 PHYSIOLOGY OF ALIMENTATION.

the pancreas changes the proferment found here into alkali-
proteinase. This function of the spleen we may no doubt
now say does not exist, and may safely attribute the results
obtained by the workers on the spleen to accidental bacterial
contamination of the extracts with which they worked. We
know now that bacteria can also activate the proferment
of alkali-proteinase, and presume that they are able to do this
because of a "kinase" which they also contain.

Attention has several times been called to the physiological
connection which exists between different portions of the
alimentary tract. It may not be amiss to do it once more
at this place. The bile and the intestinal juice, which so
markedly increase the activities of the ferments found in the
pancreatic secretion are poured into the intestine in an ap-
parently entirely purposeful manner. Bayliss and Starling
have found that pancreatic secretin, which so markedly in-
creases the discharge of pancreatic juice, increases also the
flow of bile. If a cannula is tied into the bile-duct after
previous ligature of the gall-bladder, the intravenous injec-
tion of secretin brings about not only a flow of pancreatic
juice but also an augmented flow of bile. According to De-
lezenne pancreatic secretin increases also a discharge of
intestinal juice containing enterokinase from the upper por-
tions of the small intestine. Through such means the com-
bined action of pancreatic juice, intestinal juice, and bile
upon the food as it escapes from the stomach is secured;
in other words, the conditions are established which experi-
ment has shown to be the most favorable for the rapid
digestion (and absorption) of the various foodstuffs.

CHAPTER XIV.

THE ALIMENTARY TRACT AS AN ABSORPTIVE SYSTEM.

i. The Problem of Absorption. — The problem of the ab-
sorption of foodstuffs from the alimentary tract is the same
as the problem of absorption in general. It is self-evident
that absorption and secretion are really only different phases
of the same thing, for in the one case we are asked to explain
why a tissue takes up a certain chemical substance, while
in the other we are called upon to tell how a tissue rids itself
of this same chemical substance. In the last anlaysis we
have to answer these questions for every individual cell, for
each absorbs certain substances and secretes others. Very
often one and the same cell absorbs and secretes the same
substance. As will become apparent later the intestinal
epithelium, for instance, absorbs fat from the lumen of the
gut and secretes it into the lymph stream. The lymph may
therefore be looked upon as an absorptive (fluid) tissue which
in turn becomes a secretory tissue when the body cells begin
to take the fat away from it.

Put briefly, therefore, we can say that in considering the
problem of absorption we have to answer the question, How
do the various chemical substances pass from one cell into
another, or from one cell into a liquid (such as the lymph or
blood), or finally from such a liquid into a cell? Under the
last heading comes, for example, the passage of the chemical
substances contained in the lumen of the alimentary tract
into the cells lining this tract, while the passage of these same

249

250 PHYSIOLOGY OF ALIMENTATION.

substances into the lymph or blood stream illustrates the
second of the above headings.

The natures of the chemical substances which pass in this
way from one cell to another or from one tissue into another
of necessity differ greatly from each other. Limiting our-
selves for the moment simply to the food ingested at an
ordinary mixed meal we can readily recognize the very large
number of different chemical compounds with which we have
to deal. It is possible to group all of them chemically under
a few headings, — the proteins, the carbohydrates, the fats,
the salts, and water. As the problem of absorption is a
physico-chemical one we will regroup them in a somewhat
different way as the colloids, the crystalloids, and water.

Still more difficult is it to say what forces are active in
bringing about the movement of these various chemical
substances. One of the most readily intelligible of these is,
perhaps, diffusion, which is nothing but an expression of
differences in osmotic pressure. Capillary forces must also
be considered in. a discussion of the means by which chemical
substances move from place to place. Finally we can mention
the variable mechanical affinity (Ostwald) of colloids for water
and substances dissolved in the water. The forces active
here are not as yet clearly understood. They may be capil-
lary in character or connected with the enormous surface
presented by colloids. At any rate, modern investigations
support strongly the idea that an understanding of the laws
underlying the absorption of water by colloids will do more
to give us an insight into the phenomena of absorption and
secretion than the laws of osmotic pressure and diffusion
have ever done.

But the problem of absorption is not stated when we say
that we have to explain the movement of a large number of
different chemical substances under the influence of different
forces. The activity of these forces is largely altered by the
fact that the passage of the different chemical substances
from cell to cell, or from liquid to cell, or from cell back to

ALIMENTARY TRACT AS AN ABSORPTIVE SYSTEM. 251

liquid, is modified by the existence of differences in the perme-
ability of protoplasm, more particularly by the existence of
cell membranes which arc sometimes permeable, sometimes
impermeable, or again partially permeable to a diffusing

substance. Not only do different colls differ in their perme-
ability to certain chemical substances, but the same cell may
under different conditions be at times permeable, at others
impermeable, to the same substance.

When we consider that under ordinary circumstances the
different chemical substances, the different forces, and the
different permeabilities of protoplasm are all working to-
gether in making up a picture of absorption as we witness it
in a physiological experiment some idea may be obtained
of the difficulties which face the investigator who attempts
the solution of the problem. Nevertheless great strides have
been made within recent years in substituting known laws of
physics and chemistry for the vitalistic explanations of the
older observers. In the following paragraphs are discussed
in brief the physical chemistry of the substances which serve
as food, the forces active in bringing about their absorption,
and the membranes which alter so markedly the independent
activities of the other two. It is beyond the scope of this
volume to enter more deeply than this into the subject.

2. The Physical Character of the Foodstuffs. Colloids
and Crystalloids. — From the standpoint of absorption the
chemical constitution of the foods which we consume plays
less of a role than their physical character. It is for this
reason that a regrouping of these substances into colloids^,
crystalloids, and water has been suggested, for, as we shall
see, the readiness with which they diffuse, for example, is
of greater import than (lie arrangemenl of (Ik- atoms which
constitute their molecules.

As many as lifty years ago Graham recognized that dif-
ferent chemical substances differ greatly in the rate with
which they diffuse through solvents of various kinds. Th<>se
which diffuse very slowly are h r the most part amorphous,

252 PHYSIOLOGY OF ALIMENTATION.

and since ordinary glue is an example of such he called the
substances belonging to this class colloids. On the other
hand, those which diffuse rapidly he called crystalloids, for the
bodies belonging in this class are mostly crystalline, as sugar
and salt. From the physiological standpoint of absorption
this difference in the rates of diffusion still stands as one of
the most important differences between these two classes of
compounds, for, as we shall see, our food is made up to a
large extent of typical representatives of these classes.

Modern advances in physical chemistry have given us
other criteria besides differences in the rates of diffusion and
in their amorphous or crystalline constitution by which we
can distinguish between colloids and crystalloids. When
dissolved in water or other solvents the colloids do not form
true solutions, but remain suspended in the liquid. Colloidal
solutions are, therefore, heterogeneous. More correctly put,
a colloidal solution represents a mixture of two substances
which are only partially soluble in each other. We formerly
looked upon crystalloidal solutions as homogeneous. Re-
cent experiments indicate, however, that these too are hetero-
geneous, only much less markedly so than the colloidal solu-
tions.

Solutions of crystalloids show an osmotic pressure which
is proportional to the number of particles of dissolved sub-
stance contained in the unit volume of the solvent. As
will be seen later it is upon this fact as well as upon the minute-
ness of the dissolved particles that the great diffusibility of
the crystalloids depends. In contrast herewith the so-called
" typical " colloids show no osmotic pressure and in conse-
quence do not diffuse at all. But only very few "typical"
colloids exist; the vast majority show some osmotic pres-
sure and some diffusibility, even though it be but
slight.

These enormous differences in osmotic pressure between
crystalloids and colloids correspond to similar differences in
the molecular weight of the substances composing the two

ALIMENTARY TRACT AS AN ABSORPTIVE SYSTEM. 2.*»3

classes. While the molecular weighl of mosl crystalloids

is relatively low, that of the colloids is very high. The mo-
lecular weight of glue is, for example, about G000, that of
colloidal tungstic acid 1700.

The following (able1 shows most clearly how* a high molec-
ular weight and osmotic activity are antagonistic values.
The figures refer to 10 percent solutions of the various sub-
stances.

Substance

Mol. Wt.

Osmotic Pres-
sure in Atmos-
pheres.

Depression of
Freezing-point.

Methyl alcohol. .

32

60

ISO

342

2400

13000

70.00

37 . 34

12.43

6.54

0.93

0.17

5.781

Urea . .

3.084

Glucose

1.027

0540

Albumose

0.078

Albumin

0.015

Crystalloids can, moreover, diffuse uninterruptedly through
colloidal membranes, such as animal bladders, intestines,
sheets of agar-agar, or gelatine, etc. Colloids are for the
most part unable to do this. Upon this fact is based the
principle of dialysis, in which crystalloids are separated from
colloids by placing the mixture in a tube of parchment or
an animal bladder, and hanging the whole in water or some
other solvent. The crystalloids diffuse out, leaving the
colloids behind.

It must be pointed out at once, however, that no sharp
line exists between the colloids, on the one hand, and the
crystalloids, on the other. Between the two extremes rep-
resenting the typical members of these groups there are
found an infinite number of substances, which lean more or
less strongly toward one side or the other. To illustrate
this fact we need only mention thai nol every crystalloid
diffuses through animal membranes, and not every colloid

1 Hober: Zelle und Gewebe. Leipzig, 1902, p. 19.

+-

254 PHYSIOLOGY OF ALIMENTATION.

is incapable of doing so. Moreover, certain colloids may be
obtained artificially, not only in an amorphous state but
also in a most beautifully crystalline form (Hofmeister).

So far as absorption is concerned, we can say that nearly
every food which enters the alimentary tract belongs in one
or the other of these two groups, or does so after it is acted
upon by the digestive juices. As examples of the colloids
we may mention all the different albumins, glohnlins jaUflfc
minakLs, and starch paste: under the crystalloids, the vari-
ous sugars, salts, acids, and alkalies. We begin to see now
the importance of the various digestive processes which go
on in the intestine. While it will be shown later that albu-
mins, for instance, may perhaps be absorbed as such, possibly
are even absorbed in part in an unaltered state, it is self
evident that as these colloids become more like crystalloids
their diffusibility, and in consequence their absorption, will
be greatly facilitated. In the process of digestion this trans-
ference from the side of the non-diffusible colloids to that of
the diffusible crystalloids does in fact occur. The peptones are
much less colloidal in character than the albumins from which
*hey come, and the ultimate products of digestion formed
under the influence of the proteinases or protease are prac-
tically all typical crystalloids. Starch paste also leaves the
side of the colloids when acted upon by amylase and as mal-
tose becomes grouped with the crystalloids. The fats which
as such are incapable of diffusion diffuse readily after having
been acted upon by lipase and changed into fatty acid and
glycerine.

3. Membranes. — We shall consider next not the forces that
bring about absorption, which would seem most logical, but
rather the obstacles which modify absorption — namely, mem-
branes of all kinds. This will make what is to follow more
intelligible.

As we are interested in membranes chiefly from the stand-
point of whether they allow substances to diffuse through
them or not and to what extent they permit this, the classifi-

ALIMENTARY TRACT AS AN ABSORPTIVE SYSTEM. 255

cation into s< u/ i permeable and permeable membranes is prob-
ably best suited for our purposes.

A true semipermeable membrane is one which allows only
the solvent and none of the substances dissolved in the solvent
to pass through. True semipermeable membranes are really
very rare. The existence of such membranes was discovered
by Traube, but we are indebted to Pfeffer for the idea of
supporting these in unglazed vessels of earthenware, so that
accurate studies of them could be made. The nature of true
semipermeable membranes may be made somewhat clearer
if the method of making a so-called precipitation membrane
is described.

An ordinary Pasteur-Chamberland filter is sawed in half
transversely (see Fig. 28, p. 263). The resulting small clay
cylinder after proper washing is filled with a solution of
copper sulphate, and the whole is then dipped into a second
vessel containing a potassium ferrocyanide solution. The two
solutions penetrate the unglazed clay wall from opposite
sides, meeting in the middle, where a precipitate of copper
ferrocyanide is produced.

This precipitate of copper ferrocyanide constitutes a semi-
permeable membrane, that is, one which is permeable to
water but not to substances dissolved in the water. We
must point out at once, however, that this statement is not
strictly true. It is true for the salts which have been used to
produce the precipitation membrane, but a certain amount
of nearly all other sub-stances can pass through such a mem-
brane. Strictly speaking, therefore, even the semiperme-
able membranes are permeable to some extent, though, as
we shall see, not at all to the same degree as the truly perme-
able membranes. Other precipitates have also been used as
semipermeable membranes, such as zinc ferrocyanide and
calcium phosphate, but copper ferrocyanide is perhaps the
best.

Almost any one of the animal membranes, such as the
bladder of various animals, portions of intestine, or ordinary

256 PHYSIOLOGY OF ALIMENTATION.

parchment paper, may be taken as a type of a permeable
membrane. By this is meant that these allow most crystal-
loids which are held back by semipermeable membranes to
pass through them with ease. But substances having a high
molecular weight (as the various colloids) pass through these
membranes not at all or only to a slight extent.

Do true semipermeable membranes exist in the animal
organism? So far as we know they do not. Many cells
are impermeable to a large number of substances, but all are
permeable to some dissolved substances. The red blood-
corpuscles, for example, are impermeable to many different
salts, but they readily allow ammonium compounds, urea,
etc., to pass into them. The majority of cells are even more
permeable than the red blood-corpuscles, and this even to
very large molecules. The fact that colloids can to some
extent diffuse into other colloids already points in this direc-
tion, and later we shall become acquainted with experiments
in which colloidal sodium silicate was found to be absorbed
from the intestinal tract and excreted in the urine. The
intestinal epithelium must therefore be looked upon as made
up of cells which are permeable to at least certain very large
molecular aggregates, if only sufficient time be allowed for
their absorption. But the intestinal epithelium is not equally
permeable to all substances, even when they possess approx-
imately the same molecular weight, and show in pure sol-
vents approximately the same rates of diffusion. What is
true for the intestinal epithelium holds still more when we
deal with different tissues. Each tissue varies in the ease
with which it will absorb different chemical compounds. This
selective permeability is probably more confusing in endeav-
oring to unravel the problem of absorption than any one
other factor, though, as will be seen shortly, great strides
have been made in the solution of this problem within the
last decade.

We have not as yet said where these different membranes
exist in tissues. Every cell is surrounded by a membrane,

ALIMENTARY TRACT AS AN ABSORPTIVE SYSTEM. 257

but the 'physiological membrane with which we arc dealing
here need not, and in fact usually does not, coincide with the
morphological cell-wall. This is shown particularly well in
vegetable cells in which the physiological membrane lies
entirely within the morphological membrane. Certain cells
do not have any morphological membrane at all, yet a physio-
logical membrane permeable to certain substances and im-
permeable to others no doubt exists in these cases. This is
so, for example, in the red blood-corpuscles, in amoebae, and
in the intestinal epithelium. Finally, when we deal with
tissues, whole cells arranged in layers may constitute a mem-
brane through which diffusion occurs from one medium into
another. Under these circumstances the protoplasm of the
cell, as a whole, constitutes the membrane.

What has been said of the cells themselves holds true also
for groupings of these cells as they exist in the various mem-
branes of the body — such as the absorptive mucous mem-
branes of the alimentary and urinary tracts, the synovial
membranes, etc. As the individual cells differ from each
other in permeability, so do also the various tissues built up
of these cells. In dealing with tissues we have yet to take
into consideration the permeability of the intercellular sub-
stance. This may be entirely different from the permeability
of the cells themselves.

4. The Forces Active in Absorption. — If an odorous gas
is liberated in one corner of a room, it soon spreads through-
out the whole room, so that it may be detected anywhere in
it. We say that the gas diffuses through the room, and,
according to the kinetic theory, this diffusion takes place
because the molecules <^ the gas are in constant motion and
move in all directions. The odorous gas continues to diffuse,
if nothing prevents it . until the concent rat ion of this substance
IS the same in all portions of the room.

If a substance (such a copper sulphate) is put into a

vessel and a solvent (such as distilled water) is carefully
poured upon it, we find thai after a while the soluble sub-

258 PHYSIOLOGY OF ALIMENTATION.

stance has distributed itself uniformly throughout the solu-
tion. We say that the soluble substance has diffused through
the solvent. This process of diffusion is analogous to the
diffusion of gases described in the preceding paragraph.
When a crystal of copper sulphate is covered with pure water,
the diffusion of the copper salt shows itself as a blue zone
about the crystal, which gradually spreads until all the water
is tinged uniformly blue and the crystal (provided it has not
been too large) has entirely disappeared. It is not necessary
to start with a crystal of the copper sulphate, — a solution of
this salt may be used instead and it be carefully covered
with distilled water. Diffusion occurs in the same way and
continues until the entire volume of water is tinged uni-
formly blue. What has been said holds for any solvent and
any soluble substance, be the latter a solid, a liquid, or a gas.

What is the cause of this movement of particles of dis-
solved substance from places of higher concentration to places
of lower concentration, in other words, this diffusion?

In the case of the odorous gas liberated in a room, we
attribute the spread of the odorous substance throughout the
room to the fact that its partial pressure is greater at the
point of liberation than anywhere else in the room. In other
words, the gas pressure is highest where the odorous sub-
stance is liberated, and in consequence the odorous particles
of gas are driven through the room until the pressure is every-
where the same. Entirely analogous to the movement of
the particles of a gas through a vacuum or another gas is the
movement of the particles of a dissolved substance through
a solvent, only, while we call the force which causes the move-
ments of a gas, gas pressure, we call the force which causes
the movement of a dissolved substance osmotic pressure.
Just as a gas exerts a certain (gas) pressure upon the walls
of its container, so a dissolved substance exerts a certain
(osmotic) pressure upon the walls of its container. This
pressure, indicative of the movement of the dissolved sub-
stance, we can render apparent by separating the region of

ALIMENTARY TRACT AS AX ABSORPTIVE SYSTEM. 259

higher concentration from that of lower concentration by a

semipermeable membrane. As was pointed OUl before, this
means a membrane which will not give passage to a dis-
solved substance but only to its solvent. The dissolved
substance in its movement through (he solvent is I hen slopped
by this wall, in consequence of which it exerts a pressure
(osmotic pressure) upon it which evidences itself, if the
membrane is not so supported as to prevent it, by a bulging
of the membrane toward the region of lower osmotic pres-
sure.

Just as gas pressure varies with different external con-
ditions, so does osmotic pressure (van't Hoff). Of great
physiological importance is the fact that at constant tem-
perature the osmotic pressure of dilute solutions is proportional
to the concentration of the dissolved substance. By the con-
centration of the dissolved substance is meant the number
of particles of this substance contained in the unit volume.
This, the first law of van't Hoff, means that if a solution of
a certain concentration has a certain osmotic pressure, the
osmotic pressure will be doubled if in the same volume of
solvent twice the amount of soluble substance be dissolved,
or trebled if three times the original amount goes into solu-
tion in it (see below),

Van't Hoff 's second law is also of physiological importance.
The osmotic pressure of a dilute solution is proportional to the
absolute temperature, in other words, increases as the tem-
pera! ure is increased, even when all other external conditions,
are left unchanged. The third law of van't Hoff, (hat at
the same temperature eejnol ml nines of all dilute solutions which
have the same osmotic pressure contain the same number of
molecules does not interest us in a discussion of the immediate
problem.

We have purposely spoken above of the osmotic pressure
of dissolved particles. We can say now thai wherever this
term has been used above we may substitute the word
molecules, but this only when the substance under con-

260 PHYSIOLOGY OF ALIMENTATION.

sideration is a so-called non-electrolyte, that is, a substance
which in solution in water does not conduct the electric cur-
rent. Into this group cf non-electrolytes belong, for ex-
ample, the various sugars, glycerine, and urea. Under the
electrolytes are classed all those substances which when dis-
solved in water conduct the electric current. This group is
composed of the acids, bases, and salts, the more typical
examples being the strong acids, bases, and salts, such as the
mineral acids, the caustic alkalies, and the salts formed by
the chemical union of these two.

Van't Hoff's laws do not hold in this unmodified way for
the electrolytes. Solutions of electrolytes all behave as
though they contained a larger number of molecules than is
indicated by the weight of the substance dissolved in the
water. This apparent exception to the laws of van't Hoff
has been explained by Arrhenius, who has shown that when
electrolytes are dissolved in water the molecules break up
into smaller electrically charged atoms or groups of atoms
called ions. This theory of ions is also known as the theory
of electrolytic dissociation. The degree of dissociation or
ionization which the molecules of an electrolyte undergo
varies not only with the nature of the electrolyte itself, but
also with a number of external conditions such as tempera-
ture, concentration, etc. But the amount of this dissocia-
tion can be determined experimentally, and when it is taken
into consideration the laws of van't Hoff are valid for solu-
tions of electrolytes also. Modified in this way the first law of
van't Hoff reads: The osmotic pressure of a solution is pro-
portional to the number of molecules plus ions present in the
unit volume of solvent. The word particles was used above
to cover this conception of molecules plus ions.

What has been said will serve to indicate the important
role which diffusion must play in determining the migration
of dissolved substances from regions of higher concentration
to those of lower. Because of diffusion the sugars, the salts,
and the digestion products of the proteins and fats enter the

ALIMENTARY Tit ACT As AN ABSORPTIVE SYSTEM. 261

intestinal mucosa and pass into the blood and lymph Streams.
The process of diffusion within the animal organism does not
go on as simply and as uninterruptedly, however, as in a
vessel containing a solvent and a soluble substance. The
rate of entrance of even the simplest chemical substances
into the epithelial cells of the intestinal mucosa is far dif-
ferent from the rates of diffusion of these same substances
outside of the body. As will become apparent later an
important reason for this is to be found in the constitution of
protoplasm itself, and of the membranes surrounding this
protoplasm.

CHAPTER XV.

THE ALIMENTARY TRACT AS AN ABSORPTIVE SYSTEM

(Continued).

5. The Absorption of Water. — What has gone before in-
dicates how osmotic pressure is one of the forces which deter-
mines the movement of dissolved substances. It will be
shown now that under proper conditions it becomes a force
which determines the movement of water, and that it is in
part responsible for the absorption of this substance in the
living organism. The amount of water that can be absorbed
from the alimentary tract is enormous. It is ordinarily-
stated that 4 or 5 liters of pure water may be absorbed in the
course of a day. This does not, however, indicate all that
can be absorbed. Friedrich Muller once showed in his clinic
in Munich a man who not infrequently consumed between 20
and 30 liters of beer in twenty-four hours without having a
diarrhcea. Beer does not, of course, represent pure water,
and the limits for this substance may be lower.

Osmotic pressure becomes effective in determining the
absorption of water when the diffusion of the dissolved parti-
cles to regions of a lower concentration is prevented by a
semi-permeable membrane. This may be illustrated by the
accompanying diagram (Fig. 28). A represents in cross-
section a Pasteur-Chamberland filter, in the wall of which
is deposited a semipermeable precipitation membrane M , such
as copper ferrocyanide, made as described above (page 255).
The osmotic cell, as such an apparatus is called, is closed with a
rubber stopper, C, through which passes the glass manometer

262

ALIMENTARY TRACT AS AN ABSORPTIVE SYSTEM 263

tube T. If this cell is filled with a sugar solution, and the
whole is dipped into a second vessel, H, filled with water, the
sugar endeavors to pass out into the wider (diffusion). This
movement is prevented, however, by the semipermeable

... , .,

Sugar
Solution

Water

Fig. 28.

membrane and water is in consequence drawn into the
osmotic cell, which evidences itself by a rise of the meniscus
in the tube T. The water continues to enter the cell until
the hydrostatic pressure in the lube is equal to the osmotic
pressure in the cell.

The reason why the water enters the cell, or, in general,

264

PHYSIOLOGY OF ALIMENTATION.

why water moves from a region of lower concentration to
one of higher, is not yet entirely understood. The old idea
was that the dissolved particles "attracted" the water. A
more correct explanation of the phenomenon based upon
differences in surface tension seems to be the following.
Liquids (water in this case) are surrounded by a contractile
surface film, in consequence of which they always tend to
occupy as small a space as possible (that is, tend to become
spherical). These surface films, therefore, exert a pressure
in a direction toward the centre of the liquid, as shown in
Fig. 29, a. The pressure exerted by the diffusion of dissolved
particles is evidently opposite in nature to that exerted by

Fig. 29.

such surface films, for the particles of a dissolved substance
move from the centre toward the surface of a liquid and
press upon it. This is indicated in Fig. 29, b. In the vessel
B in Fig. 28, which contains only pure water, we are dealing
with surface tension only, which we will represent by P.
In the osmotic cell we have this same surface tension, but it
is counteracted by the osmotic pressure p. Evidently, there-
fore, PyP—f. Or, to put the same in words, the surface
tension of the water outside of the cell is greater than the
surface tension inside of the cell minus the osmotic pressure.
Water passes from the outer vessel into the cell, therefore,
because it is squeezed in and not because it is pulled in.

It is clear that what has been said regarding pure water

ALIMENTARY TRACT AS AN ABSORPTIVE SYSTEM. 265

and a sugar solution holds for any pure solvent and any solu-
tion. Furthermore, it holds for any two solutions which
have not the same osmotic pressure (that is to say, have no!
the same number of particles dissolved in the unit volume
of solvent). The solvent moves always from the region of
lower concentration to that of higher concentration (thai is,
from the region of lower osmotic pressure to the region of
higher) when the two are separated by a semipermeable
membrane, and this movement continues until the osmotic
pressure on both sides is the same. It is clear, therefore,
that if the osmotic cell is filled with water instead of with a
sugar solution and the surrounding vessel contains a sugar
solution, or, to put it more generally, if the osmotic cell con-
tains a solution of a lower concentration than the surrounding
vessel, the water will move out of the cell into the solution in
the outer vessel until the osmotic pressure on both sides of
the membrane is again the same.

Do similar conditions exist in the case of the body cells?
To a certain extent they do. It was pointed out above that
many cells which have been studied seem to be surrounded
by membranes which have to be considered as approxi-

mating true semipermeable ones more or less perfectly.
Certain cells even seem to possess membranes which arc truly
semipermeable for a large Dumber of substances. Fig. 30
illustrates the behavior of any cell possessing a truly semi-
permeable membrane towards solutions *>( various kinds.
If we consider b the cell under normal physiological con-

266 PHYSIOLOGY OF ALIMENTATION.

ditions, that is, as in osmotic equilibrium with the liquids
with which it is bathed, then a and c represent respectively
the effect upon this cell of immersion in a solution more
dilute or more concentrated than that in which it is immersed
normally. If the cell is placed in a solution which has a
lower osmotic pressure than the cell contents, then water
will pass into the cell until the osmotic pressure on both sides
of the (physiologically) semipermeable membrane is the same.
The cell will in consequence increase in size (if some external
obstacle does not prevent it) and may swell so much that
the cell-wall is ruptured and the cell contents are allowed
to escape. The reverse must occur when the cell is immersed
in a fluid having a higher osmotic pressure than the cell
contents. Under these circumstances water passes through
the semipermeable membrane surrounding the cell in the
direction from within outwards until osmotic equilibrium
is once more restored. As the water passes out of the cell,
this shrinks, and the amount of the shrinkage is determined
by the amount of water given off by the cell. This in turn
is determined by the amount of the difference between the
osmotic pressure of the cell contents and that of the sur-
rounding liquid.

True semipermeable membranes are rarely found sur-
rounding any cells that have been accurately studied, and
so it will not seem strange that physiological experiment
has shown that the epithelial cells of the alimentary tract
obey the ordinary laws governing the osmotic absorption
of water only when exposed to great and sudden changes
by being flooded with solutions of very high or very low
osmotic pressures. The reason for this is readily intelligible
when it is remembered how very permeable the alimentary
mucosa must be to allow the passage of the host of soluble
substances which daily pass through it into the blood or
lymph or from these circulating fluids out into the lumen
of the digestive tube. Whenever a membrane allows the
passage of a substance dissolved in a liquid found on either

ALIMENTARY TRACT AS I.V ABSORPTIVE SYSTEM. 2G7

side of it, Him differences in osmotic pressure are quickly
equalized through diffusion of the dissolved particles, and a
movement of water can in consequence show itself only
imperfectly.

But the cells of the alimentary mucosa are by no means
equally permeable to nil dissolved substances. For this rea-
son the cells of the alimentary tract (as well as other body
cells) obey the laws of osmotic pressure more perfectly when
certain substances are dissolved in the fluids present in the
alimentary tract than when others are concerned. A partial
explanation at least of this selective permeability of cells will
be given when we discuss Overton and Meyer's work on the
lipoids.

We have yet another way of influencing the absorption of
wrater besides through differences in osmotic pressures, and
that is by changes in the affinity of the colloids for water. As
is well known protoplasm is composed of a mixture of col-
loids^ and experiment has shown that the amount of water
absorbed by colloids can be enormously influenced by a num-
ber of external conditions. As shown by such experiments
as those of Hofmeister,1 gelatine plates absorb water from
the chlorides of the alkali metals. They absorb much more
from isotonic solutions of the bromides and nitrates of these
same metals. The citrates, sulphates, and tartrates of these
metals, on the other hand, cause such swollen plates to give up
their water.2 It almost seems as though in an understanding
of the laws governing the absorption of liquids by colloids, and
of the secretion of these same liquids when external con-
ditions are slightly altered, lies the explanation of much that
is obscure in the phenomena of absorption and secretion as
they are found in the animal and vegetable organism.
Chanu'es in osmotic pressure are certainly by themselves in-

1 Hofmeistkr: Aicliiv f. oxp. Patli, XXVIII, p. 210.
'This almost seems analogous t<> 1 1 1<> secretion <>i water into the
alimentary tract under the influence of cathartic salts.

268 PHYSIOLOGY OF ALIMENTATION.

adequate to explain more than a few of the facts observed
experimentally in these fields. Perhaps pathology may also
find help here.1

6. Lipoidal Absorption. — If a cell (such as a red blood-
corpuscle) possessing a semipermeable membrane is put into
a series of differently concentrated solutions of a certain
substance it will show no change in volume (will not shrink
or swell) in that solution which has the same osmotic
pressure as the cell contents. Such a solution is said to be
isosmotic or isotonic with the cell contents. If, now, solutions
of different substances are prepared a certain concentration
can be found for each of these in which the cell used for study

1 On the hypothesis that cedema represents an increased affinity of
the colloids of the tissues for water brought about through the presence
in them of abnormal substances capable of increasing this affinity I
have made a series of experiments which seem to support this idea.
Not only does calculation show that the maximum amount of water
ever held by a tissue in cedema at no time exceeds the amount easily
absorbed by a gelatine plate, but acids and certain salts which increase
the affinity of gelatine plates for water increase in a similar way the
affinity of frog's muscles, connective tissue, etc., for water. In cedema-
tous tissues we have not only the presence of an increased amount of
C02, but also organic acids of various kinds, and these present in con-
centrations which readily increase the affinity of ordinary gelatine plates
for water some 30 or 40 percent. Many poisonous substances — such
as the irritant oils — which by themselves do not increase the affinity
of a gelatine plate for water, nevertheless bring about an cedematous
swelling when applied to living tissues, apparently because they lead
to an altered metabolism of the cells concerned which brings with it
the production of substances which do increase the affinity of colloids
for water. An attempt to show that such substances are present in
cedematous tissues lead to the experiment of introducing frog's gas-
trocnemii into the peritoneal cavities of normal rabbits and rabbits with
an ascites due to the injection of uranium salts. In spite of the isoton-
icity of the normal and abnormal peritoneal fluids the frog's muscles
contained in the ascitic rabbits weighed 20 to 30 percent more at the
end of several days than those in the healthy rabbits. The blood-serum
of an ascitic rabbit will, moreover, upon injection, bring about an
cedema in a healthy one.

ALIMENTARY TRACT AS AN ABSORPTIVE SYSTEM. 209

shows no change in volume. Since ;ill of these solutions
must then be isosmotic with the cell contents they must also
be isosmotic with each other. The red blood-corpuscles (and
other cells) have been employed in this way for the determi-
nation of osmotic pressure. But this is true only when
the cell has a true semipermeable membrane, and such
exist practically nowhere in living organisms. As the num-
ber of substances studied with reference to their power of
changing the volume of red blood-corpuscles (or causing them
to give up their red coloring-matter or "plasmolyzing"
various plant-cells, etc.) increased it was soon found that
there exist a large number of substances which affect
the cells either at no concentration at all or only when
present in amounts greatly exceeding the ordinary limits
at which a change in volume might be expected. Atten-
tion was called to this fact when it was pointed out that the
cells of the alimentary mucosa swell or shrink only when
exposed to great and sudden changes in osmotic pressure
through the fluids surrounding them. These substances
which in solution failed to bring about changes in the volumes
of cells in proportion to their osmotic pressure existed for a
long time as unexplained exceptions until Overton and
Meyer made a systematic study of them and so advanced
most markedly our knowledge of the fundamental character
of absorption and secretion.1

The power of a solution to abstract water from a cell (that
is, to shrink or "plasmolyze" it) is dependent upon the semi-
permeability of the membrane surrounding the cell to the
substance dissolved in the solution. If the substance is

1 Overton: Vierteljahresschrift d. naturforsch. Gesellsch. in Zurich,
1895, XL, p. 1, and 1S99, XLIV, p. SS; Zeits.hr. l". physik. Chemie,
1S97, XXII, p. 1S9. Meyer: Arch, t exp. Path. u. Phann., l.v.t't.
XIII, p. 109, and 1901, XLVI, p. 338. This accounl is largely taken
from Hober's excellent Physikalische I Ihemie der Zelle und An- Gewebe,
Leipzig, 1902, p. 101. See also Spiro: Physikalische und physiolo-

gische Selection. St r:i>sl>urg, IS'.iT.

270 PHYSIOLOGY OF ALIMENTATION. <

able to pass through the cell membrane plasmolysis must
in consequence be impossible, for under these circumstances
the diffusion of the dissolved substance into the cell equalizes
the pressure on both sides of the membrane, and the difference
between the osmotic pressure inside and outside of the cell
which is essential for plasmolysis does not come to pass. A
movement of water does not occur in the direction toward
the region of higher osmotic pressure as when a semipermeable
membrane is present, but a movement of dissolved particles
takes place from the region of higher osmotic pressure to that
of lower osmotic pressure. Only in case the cell membrane
possesses but a limited permeability do both water and dis-
solved substance move, for in this case a cell will give up
some of its water to the more concentrated solution surround-
ing it before the substance dissolved in this solution has had
time to diffuse into the cell. Under such circumstances a
temporary change in the volume of the cell concerned is pos-
sible. Herein lies the explanation of the behavior of the
cells of the alimentary mucosa in responding only temporarily
to great and sudden changes in the osmotic pressure of liquids
surrounding them.

But the intensity with which a solution can bring about
the plasmolysis of a cell is a function not only of the degree
of difference between the osmotic pressure without and
within the cell, but also of the velocity with which the sub-
stance can penetrate the cell membrane. It is evident that
with the same degree of osmotic difference a substance capa-
ble of diffusing rapidly into a cell will be less likely to plas-
molyze the cell than one which diffuses in more slowly, for
under the latter circumstances a movement of water is more
likely to occur than under the former.

It becomes possible to differentiate in consequence be-
tween substances which enter cells slowly and those which
enter rapidly. Glycerine belongs to the class of substances
which diffuse slowly into a cell and as slowly leave it. If
algse are in consequence placed in a dilute glycerine solution

ALIMENTARY TRACT AS AN ABSORPTIVE SYSTEM. 271

and the concentration of this is allowed to increase slowly
through evaporation the algse suffer no change, for each in-
crease in the concentration of the glycerine solution has time
to be equalized by an increase in the concentration of the
glycerine within the cell. But if the algse be removed from
the now concentrated solution of glycerine and dropped into
clear water they burst at once, for in so short a time the
glycerine has not had time to diffuse out of the cells.

Methyl alcohol belongs, on the other hand, to the sub-
stances which can rapidly pass through cell membranes.
The root hairs of Ht/jrocharis plasmolyze in a cane-sugar
solution having a concentration between 7 and 1\ percent.
Plasmolysis occurs in the 1\ percent solution in 10 seconds.
If 3 percent of methyl alcohol are added to the 7 percent
cane-sugar solution its osmotic pressure is made to equal a
35 percent cane-sugar solution. Yet in this mixture of
sugar and methyl alcohol no plasmolysis occurs, for the
methyl alcohol diffuses almost instantaneously through these
cells so that the great difference between the osmotic pres-
sure within and without the cells cannot become effective.
(Overton.) 1

To the compounds which diffuse rapidly into protoplasm
belong the monatomic alcohols, aldehydes, and ketones, the
hydrocarbons with one, two, and three chlorine atoms, the
nitroalkyls, the alkylcyanides, the neutral esters of inorganic
and many organic acids, anilin, etc. The diatomic alcohols
and the amides of monatomic acids pass into cells more
slowly, and still more slowly glycerine, urea, and erythrite.
The hexatomic alcohols, the sugars with six carbon atoms
(hcxoses), the amino-acids, and the neutral salts of the organic
acids diffuse into cells only very slowly. The entrance of
these various substances into the cells is rendered apparent
by yet other signs than a failure of plasmolysis, such as evi-
dence of narcosis or other intoxication, the formation of pre-

1 Cited from Bober: 1. c, p. 105.

272 PHYSIOLOGY OF ALIMENTATION.

cipitates, etc., but the details of these experimental findings
must be sought in the original publications.

A simple glance at the table given in the last paragraph
shows that we have to deal with all manner of chemical sub-
stances, from those relatively simple in composition to those
very complex, some of physiological importance and found
as normal constituents of the living cell, others entirely
foreign to the living organism. What physico-chemical
character have all these substances in common which
allows them to penetrate living cells more or less readily
and so modify the otherwise simple osmotic behavior of
cells in general?

An explanation frequently given and long believed to be
the correct one is that the size of the molecules is the con-
dition which determines the entrance of the dissolved particles.
According to this conception the cell membranes may be
regarded as sieves which allow all molecules that do not
exceed a certain size to pass into the cell, while those larger
than this are held back. The deficiencies of such an explana-
tion are at once apparent when it is remembered that mem-
branes which readily give passage to such large atomic aggre-
gates as the alkaloids or sodium salicylate hold back the
much simpler amino acids and potassium sulphate.

According to Overton all the substances enumerated above
enter cells because the membranes surrounding them behave
like films composed of a substance which in its properties as a
solvent is not unlike ether or the fatty oils. For this reason all
those substances which are more soluble in such ethereal or
oil-like substances than in water enter the cell and this the
more rapidly the greater the solubility of the substance in
the ethereal or oil-like substances as compared with water;
in other words, the greater the distribution coefficient between
the film surrounding the cell and water. This distribution
coefficient is, at the same temperature, independent of the
concentration of the substance. This means that if a sub-
stance soluble in any two solvents is offered these simulta-

ALIMENTARY TRACT AS AN ABSORPTIVE SYSTEM. 273

oeously (for example, .succinic acid to a mixture of equal parts
of water ami ether) the proportion of this substance found
in solul ion in each of the solvents will always be the same no
mat ler how much of the substance is offered the two solvents.
This means that if of six grams of succinic acid offered a
certain volume of ether and water, five grams are found to
1 issolve in the ether and one in the water, then if twelve grams
I) - offered the two solvents, ten will dissolve in the ether and
t wo in the water. The proportion of 5 : 1 is therefore main-
tained.1

With these ideas in mind it is only necessary to reexamine
the list of substances which experiment has shown enter
cells more or less rapidly and see if they are not all of
a character which are more soluble in ethereal or oily sub-
stances than in water, and that those which stand first in the
list and consequently enter cells most rapidly are not such
as have the highest distribution coefficients. An illustration
may make this clearer. The repeated substitution of an
at "in or a group of atoms for some other atom or group of
at "ms in a chemical compound is often accompanied by
marked changes in the solubility of this compound and its
derivatives. Glycerine enters a cell only very slowly. When
an atom of chlorine is introduced into this compound it
enters protoplasm more rapidly, and when two are introduced
still more rapidly, for these derivatives are more readily
soluble in fats than the original glycerine. The same holds
true of urea and its methylated derivatives. While urea
diffuses but slowly into cells, the introduction of one, two,
or three methyl radicles into this compound increases pro-
gressively its solubility in fats and hence the rate of diffusion
into living cells.

Having shown that the entrance of many different sub-
stances into cells is dependent upon their solubility in fat-
like bodies we may ask more specifically, What are these

1 See Hober: 1. c, p. 111.

274 PHYSIOLOGY OF ALIMENTATION.

substances in the cell? By making use of the so-called
"vital" staining methods, that is through use of stains which
will color living protoplasm, Overton has been able to show
that these fat-like bodies — or as they are collectively called,
the lipoids — are cholesterin, lecithin, protagon, and cerebrin.
These substances are not, of course, true fats, but they re-
semble these in their property of dissolving more or less
readily the compounds which were found above to enter
living cells. The conception that living cells are surrounded
by lipoidal membranes seems, therefore, not to lack experi-
mental support, and osmotic pressure as a force determining
the movement of dissolved particles and of water becomes
a more clearly defined force in phenomena of absorption and
secretion when this selective power of solution of the surface
films of cells is taken into consideration.

It must not be thought, of course, that these conceptions
of cell membranes and the movement of water and dissolved
substances through them, as outlined for cells in general and
applicable to the alimentary mucosa in particular, explain
more than a part of the phenomena of absorption and secre-
tion as illustrated by the gastro-intestinal tract. Even in
this statement we are not considering the absorption or
secretion of substances which before or during their passage
through the alimentary mucosa suffer a change, such as the
fats, proteins, and carbohydrates. All this will become more
apparent in the discussion of the absorption of the specific
elements of our food, when a mass of isolated facts will be
found that still lack a unifying explanation.

7. The Absorption of Salts.— Recognized physical laws suf-
fice at present to explain only a part of the phenomena ob-
served in the absorption from the gastro-intestinal tract of
even such simple substances as the salts. From some points
of view the absorptive mucous membrane behaves like a dead
diffusion membrane on one side of which there is found the
blood, the composition of which may be looked upon as fairly
constant, on the other the salt solution undergoing absorption.

ALIMENTARY TRACT AS AN ABSORPTIVE SYSTEM. 275

A salt solution will, in the course of time, \>r absorbed by the
alimentary tract no matter whether it be isotonic, hypertonic,
or hypotonic with the blood, but the rule differs with the
different kinds of salts. Different observers agree that
when a hypertonic solution is introduced into the intestine
its volume increases at first through a diffusion of water
into it, while its concentration diminishes. At the same
time certain constituents of the blood diffuse into it.
After this the volume of solution in the intestine gradually
diminishes. These phenomena are usually explained on the
basis that the salt diffuses into the blood because its concen-
tration in the lumen of the alimentary tract is higher than the
concentration of this same salt in the blood, while various
constituents of the blood diffuse out into the intestine for
the same reason. The initial increase in the volume of the
solution is explained in those cases in which it occurs on the
basis that the salt under consideration does not diffuse rapidly
enough not to allow osmotic differences to make themselves
felt through a migration of water. For this reason, too, it
is found that the originally hypertonic solution gradually
approaches isotonicity with the blood.

When we deal with the diffusion of a hypotonic solution
water diffuses into the blood because of osmotic differences,
and the salt solution under these circumstances also ap-
proaches isotonicity with the blood. When this occurs the
concentration of the salt in the solution undergoing absorp-
tion is increased and so is placed in a position to diffuse into
the blood, but this lowers the osmotic pressure of the solu-
tion in the lumen of the intestine once more, in consequence
of which water is again absorbed from it by the blood; and
so these processes repeat themselves until all the salt solution
is absorbed.

Solutions isotonic with the blood arc absorbed quite as
easily as hypertonic or hypotonic ones. It is somewhat dif-
ficult to see what forces are active in bringing about the
transport of the solution into the blood. The explanation

276 PHYSIOLOGY OF ALIMENTATION.

ordinarily given is as follows: While the inorganic constitu-
ents of the blood may diffuse out into the lumen of the intes-
tine, the organic constituents (the albumin, globulin, etc.),
because of their colloidal nature, are practically unable to
do this. While colloids exert no great osmotic pressure they
nevertheless exert some, and so, even after all other osmotic
differences on both sides of the diffusing membrane have been
equalized, an excess of osmotic pressure must remain on the
side of the blood. This would then lead to the abstraction of
a small amount of water from the solution in the intestine
which would in consequence be rendered hypertonic. Salts
would then diffuse into the blood, then more water, until,
little by little, the whole would be absorbed.1

For a large number of salts the rate of absorption is propor-
tional to the velocity of their diffusion (Hober2). In the
following table are arranged a number of salts in the order of
their diffusion velocities. When arranged in the order of the
velocity with which these salts are absorbed from isotonic
solutions when equal amounts are introduced into closed
loops of intestine the grouping remains the same.

Sodium chloride

Sodium nitrate
Sodium lactate

Sodium sulphate

Sodium malonate

Sodium succinate

Sodium tartrate

Sodium malate

Magnesium chloride
Calcium chloride

1 More detailed discussion of these still unsatisfactory theories of
absorption cannot be entered into here. See Hober: Physikalische
Chemie d. Zelle u. d. Gewebe, Leipzig, 1902, p. 184; Pfluger's Archiv,
1898, LXX, p. 624. Starling: Journal of Physiology, 1896, XIX, p.
313. Kovesi: Centralbl. f. Physiol., 1897, XI, p. 553.

2 Hober: Pfluger's Archiv, 1899, LXXIV, p. 246. Zelle una
Gewebe, Leipzig, 1902, p. 190.

ALIMENTARY TRACT AS AN ABSORPTIVE SYSTEM. 277

Sodium chloride has, of all these salts, the greatest diffusion
velocity, and also the greatest absorption velocity. From
here downwards the velocities of diffusion and of absorption
diminish progressively. In the same unit of time a larger
amount of the solution of a salt in the first group will dis-
appear from a loop of intestine than of an isotonic solution
of a salt contained in the second group, and this will dis-
appear sooner than an equal amount of an isotonic solution
of a salt found in the third or fourth group. For all salts this
does not hold, however. Of the halogen salts of sodium, for
example, which have all the same diffusion velocity, the
chloride is absorbed most rapidly, then the bromide, and
finally the iodide. All fluorides are absorbed exceedingly
slowly, as also the carbonates, due no doubt to secondary
changes produced in the cells, for the fluorides are proto-
plasmic poisons, and the carbonates suffer a hydrolytic disso-
ciation with the formation of free OH ions, which are toxic
in even very low concentrations.

Hober has made interesting observations on the paths of
absorption of the salts. From studies with dyes which are in
part soluble in the lipoids of the cells, in part insoluble, he
has been able to show that salts are for the most part absorbed
only intercellularly; that is to say, they pass into the blood
not through the epithelial cells of the absorbing mucosa,
but through the intercellular spaces. If solutions of the salts
of various dyes soluble in the lipoids of the cell — such as
methylene blue, toluidin blue, or neutral red — are introduced
into the intestinal tract of frogs, microscopic examination
shows that the dyes affect slightly all portions of the ab-
sorbing mucosa. But while protoplasm, nucleus, and intercel-
lular substance are scarcely colored, granules contained within
the protoplasm take up the dyes most intensely. The granu-
lar material seems to be, therefore, an excellent solvent for
these dves and probably consists of those substances which
are collected under the heading lipoids. Whim solutions of
dyes insoluble in the lipoids— such as water-soluble aniline

278 PHYSIOLOGY OF ALIMENTATION.

blue, water-soluble nigrosin; or benzoazurin — are introduced
into the intestine the urine becomes colored, yet no deeply
stained granules are found in the protoplasm.

These observations only show that the intestinal epithelium
is permeable to salts soluble in the lipoids; it does not as yet
prove that those insoluble in the lipoids are absorbed only
interepithelially. But this is rendered probable as soon as
fixing agents, such as ammonium molybdate, osmic acid,
corrosive sublimate, picric acid, ammonium picrate, tannic
acid, or gold chloride, are used to fix the pictures obtained
after simple introduction of a dye into the intestinal tract.
Under these circumstances it is found that if the fixing agent
is one soluble in the lipoids of the cell (such as osmic acid),
the granular pigmentation of the cell found after the use of
such a dye as methylene blue remains unchanged. If, how-
ever, a fixing agent insoluble in the cell lipoids (such as am-
monium molybdate, which is able to plasmolyze cells) is used,
the blue granules in the cell are seen to dissolve, to move
toward the periphery of the cell and to be precipitated here.
This is because the ammonium molybdate remains in the
intercellular spaces and precipitates the dye present here.
In this way the equilibrium between the dye without and
within the cells is destroyed. The stain in consequence begins
to move out of the cell toward its periphery, where it meets the
ammonium molybdate. What has been said of this fixing
agent holds for every one of the fixing agents capable of re-
acting with the stains employed and not soluble in the lipoids.
With this is proven quite conclusively that salts insoluble
in the lipoids make their way from the intestine into the blood
only through the interepithelial spaces.1

This is, perhaps, the best place to touch briefly upon the
absorption of such compounds as alcohol, urea, and certain

1 It might seem from this that the ordinary salts are entirely in-
capable of entering the epithelial cells of the intestine or any other
cell containing lipoids. This is not true, but the means by which
they may or do enter cannot be dealt with here.

ALIMENTARY TRACT AS A A' AliSolil'TlVL SYSTEM. 279

oilier substances which are absorbed from the alimentary
trad much more rapidly than the inorganic salts. While
the absorption of salts from the stomach is still questioned,
the rapidity with which alcohol disappears from the gastric
contents is truly phenomenal. Urea also is much more
rapidly absorbed than salts of a simpler composition. The
reason for this is at once apparent when we assume that
while the inorganic salts can pass into the blood only through
the intercellular spaces, alcohol, urea, etc., are soluble in the
lipoids, and so can pass directly through the epithelial cells
as wrell.

From what has been said it seems, therefore, as though the
behavior of the epithelial cells of the gastro-intestinal tract
toward certain soluble substances is not unlike the behavior
of cells in general, and is dependent upon the same powers of
selective solution by their surface membranes.

We come now, however, to a series of facts for which an
adequate physical explanation is entirely lacking. These
facts are connected with the predominant 'permeability of the
gastro-intestinal tract in one direction. While, as already s ta ted,
some of the constituents of the blood may diffuse into a solu-
tion contained in the lumen of the intestine, only very little
passes out in this way. Salts found in the blood pass only
in exceedingly small amounts, if at all, into the intestine,
while these same salts in various concentrations pass easily
from the alimentary lumen into the blood. It is evident that
every constituent of the blood, which, like the albumin and
the globulin, is unable to pass into the intestine can in this
way become effective in absorbing water, and in consequence
lead to a passage of salt from the fluid in the alimentary tract
into the blood. This semi-permeability of the absorbing
mucosa in one direction only would therefore greatly
favor the absorption of substances from the lumen (Conx-
beim).

All our attempted physical explanations of absorption by
the alimentary mucosa fail when v.e approach the observa-

280 PHYSIOLOGY OF ALIMENTATION.

tions of Heidenhain,1 Reid,2 and Cohnheim. Heidenhain
found that when a dog's own blood-serum is introduced into
its intestinal tract it is absorbed. Reid removed the intestine
from rabbits at the height of digestion and found when this
is cut open and stretched between two isotonic sodium chlo-
ride solutions that the salt solution is pumped from the side
of the mucosa toward the serosa. Cohnheim found that when
the alimentary tract is removed from certain marine animals
(Holothuria tubulosa), and this is filled with 10 to 30 c.c. of
sea-water, and the whole is then suspended in sea-water,
that this moves from the alimentary tract out into the sur-
rounding water. In all these experiments we have no dif-
ferences in osmotic pressure, and at present we cannot say
what makes the liquids move. The death of the cells, or
certain poisons such as sodium fluoride, arsenic, or chloro-
form, do away with this transport of serum, sodium chloride
solution, or sea-water from the side of the mucous mem-
brane toward the serosa, and make the alimentary wall act
like an ordinary dead diffusion membrane. But it explains
nothing, of course, when we say that such a transport is
dependent upon the living activity of the cells.

The predominant permeability of the intestinal tract in
one direction can be markedly influenced experimentally.
When a dextrose solution is introduced into a loop of small
intestine, it is absorbed. According to experiments carried
out by Gertrude Moore and myself this same glucose solu-
tion when injected into the blood is not excreted into the
lumen of the intestine. This happens, however, as soon as
certain salts (such as sodium chloride) are injected along
with the sugar solution, presumably because these salts
modify this predominant permeability in one direction. The
intestine in consequence now excretes a substance which it

1 Heidenhain: Pfluger's Archiv, 1894, LVI, p. 579.
?Reid: Phil. Trans. Royal Soc, 1900, CXCII, p. 231. Journal of
Physiol., 1601, XXVI, p. 436.

ALIMENTARY TRACT AS AN ABSORPTIVE SYSTEM. 2S1

absorbed formerly. What has been said of dextrose holds
also for a number of other substances.

The different portions of the alimentary tract absorb salts
in very different amounts. Under ordinary circumstances
the amount of salt absorbed in the mouth or oesophagus is
to be looked upon as practically nothing. While certain au-
thors believe that considerable amounts of salt are absorbed
in the stomach, others question it entirely. The small in-
testine absorbs salts freely throughout its entire length,
though the jejunun seems to be somewhat more active in this
regard than the ileum. The large intestine also takes up salts,
but not to the same extent as the small bowel.

Under certain circumstances one region of the alimentary
tract may absorb a salt while another is excreting this same
salt. One and the same portion of the intestine may even
absorb a salt which under somewhat different conditions it
excretes. The character of the changes which take place
in the absorbing structure of the alimentary tract to render
such phenomena possible are not as yet understood, and the
visible alterations (swelling, contraction, coagulation) often
observed in the absorbing surfaces still lack a unifying
physical explanation.

CHAPTER XVI.

THE ALIMENTARY TRACT AS AN ABSORPTIVE SYSTEM

{Continued).

8. The Absorption of Carbohydrates. — The carbohydrates
which are of chief importance in the physiology of alimenta-
tion in so far as they are found in any ordinary mixed meal,
"4r are the polysaccharides starch, glycogen, and cellulose, the
it disaccharides- cane-sugar, malt-sugar, and milk-sugar, and
f | fjie monosaccharides dextrose. IsRvulose. and galactose. Of
the polysaccharides the starches make up not only the bulk
of this class of food, but of all the carbohydrates that are
enjoyed in an ordinary diet. The consumption by an ordi-
nary individual of several hundred grams of starch a day in
the form of bread, potatoes, beans, etc., is not uncommon.
A few grams of glycogen enter into the ordinary daily diet as
constituents of lean meat, liver, etc. Cellulose is obtained
through the vegetable constituents of the diet, more particu-
larly celery, string beans, turnips, carrots, beets, etc.

Sucrose (cane- or beet-sugar) as the ordinary sugar of com-
merce and the recognized sweetening agent of our food makes
up the bulk of the disaccharides which we consume, though
the exact amount consumed in a day is subject to the widest
individual variations. Malt-sugar is obtained in small
amounts through beverages and "breakfast foods," into the
composition of which sprouted grains enter. Milk-sugar
comes to us through milk and certain of its derivatives; only
rarely as a distinct addition to an ordinary mixed diet.
Dextrose and laevulose are found in certain fresh and dried

282

ALIMENTARY TRACT AS AN ABSORPTIVE SYSTEM. 283

fruits, and in the commercial "glucoses" (corn-sugar, molas-
ses, etc.)- The dextrose ;hm1 la-vnlose found in the alimentary
fr-wi ja derived with the exceptions indic-i led, from the de-
ipositioTi of the polysaccharides :ind disaccharides of the

udiet. Galactose enters as such into the diet practically nol al

all. 11 is pfodjififid in the alimentary tract thron.fh Hie actio^

,of lada.se upon it | j 1 1- -.-<n<--.-i t Either directly or indirect ly.d^x^
Jaxise_Jpecomes the predominating sugar of the alimentary
tract. Not only does it constitute the bulk of the com-
mercial "glucose," but it appears as the ultimate product of
the decomposition of every polysaccharide and disaccharide.
Glycogen is split directly into dextrose through amylase. The
same ferment converts starch into maltose, which through
maltase is converted into dextrose. Dextrose appears as one-
half of the product of the action of sucrase on sucrose, and
lactase on lactose. Cellulose, though acted upon only by the
bacterial enzymes of the alimentary tract, yields dextrose
when this occurs.

We have to ask now in what form the carbohydrates of
the diet are absorbed. There seems to be little doubt that
the monosaccharidesjiro absorbed as such. With the disac-
charides matters are somewhat different. If sucrose, maltose,
or lactose are fed slowly, they are all converted into mono-
saccharides before they are absorbed. When, however, those
disaccharides are, fed rabidly,, then they are not all split
before they are aosorbed, ana sucrose, maltose, and lactose
may be recovered as such from the blood and from the urine,
for these disaccharides when present in the circulating blood
in a concentration exceeding a very small fraction of a per-
cent are eliminated through the kidneys. Ordinarily it is
said that the disaccharides appear in the blood and the urine
if they are fed in too large amounts. This is nol the essential
factor, however, but the time taken in feeding the amount,
for if the sugar solution is not absorbed too rapidly it does
not pass over into t he blood in an unchanged state.

Starch, glycogen, and cellulose all being colloidal bodies arc

284 PHYSIOLOGY OF ALIMENTATION.

unable as such to pass through the walls of the alimentary
tract. They must be acted upon by the enzymes found
here before they can be absorbed. The starch may be ab-
sorbed as soon as it has been broken down to the maltose
stage, but most of it seems to be absorbed in the form of
dextrose. The glycogen is readily converted into dextrose
and is as rapidly absorbed. The cellulose of the food is
ordinarily classed as a substance which is of no use from a
nutritional standpoint, for it cannot be absorbed as such
and no enzymes are secreted by the alimentary tract which
can act upon it. Only the cellulose-splitting ferment (cytase)
contained in certain of the bacteria found in the alimentary
tract is able to convert cellulose into sugar, and experiment
shows that the amount produced in this way is exceedingly
small.

Of great interest from a medical standpoint are the ex-
periments of Hofmeister,1 who has determined the "assimila-.
t[nn limijallof various carbohydrates. By the assimilation
limit (which is not a well-chosen term) Hofmeister under-
stands the amount of a sugar that may be administered to an
animal without the appearance of sugar in any form in the
urine. It is clear that a large number of factors play a role
in this complicated picture, and it is not strange that the
figures obtained should vary widely from each other. Never-
theless the general conclusions which may be drawn are
clear enough and are valuable in any dietary scheme in which
the quality and quantity of carbohydrates administered plays
f a role. It has been found that the assimilation limit of any
sugar is different not only in different animals, but varies in
one and the same animal under different physiological con-
ditions, such as the rapidity with which absorption takes
^ place, the amount of sugar already present in the blood, and
the nutritional state of the animal as a whole. A dog that has
been starved for a number of days will excrete sugar in the

1 Hofmeister: Arch. f. exp. Path. u. Pharm., 1889, XXV, p. 240,
and 1890, XXVI, p. 350.

ALIMENTARY TRACT AS AN ABSORPTIVE SYSTEM. 285

urine after being fed 10 to l."> grams of starch paste, while a
healthy dog will stand several times this amount at a single
feeding and not excrete sugar.1 Most striking is the assimi-
lation limit of one and the same animal for different kinds of
carbohydrates. -jOnlmary starch Uadi '-11 the lll1"1!^ in t|ic
amount that may he consumed in twenty-four hours (mori-
than 500 grains) without the appearance of sugar in the
urine. Next in order stand dextrose, lsevulose, sucrose, mal-
tose, and lactose in the order named. The reason why the
disaccharides stand lowest is no doubt to be sought in the
fact that when these are fed rapidly and in large amounts,
they pass without change into the blood, ^a^^s^r^eJiGj^yr
and muscles retain the disaccharides but imperfectly, their
concentration in the blood soon exceeds the limits at which
the sugar passes over into the urine.

The rapidity with which the different sugars are absorbed
seems not qt, all dependent rp"^ tbfiM nTP<a of diffusion or
differences in osmotic pressure The subject has been investi-
gated by Albertoni,2 Rohmaxn and Nagano.3 Sugars are
absorbed not only from solutions which are hypertonic or iso-
tonic with the blood but also such as are hypotonic. When
isosmotic solutions of sugars are compared it is found that dex-
trose is a_hsorberj most rapidly, sucrose next, and much more .
slowly lactose. But the amount absorbed in any unit of time
varies, much more of any given sugar being absorbed in the
first hour after feeding than in subsequent hours. Starch,
as already pointed out, cannot be absorbed as such. Its
absorption is dependent upon the velocity with which it is
split into absorbable sugars. These sugars .amder normal
circumstances are absorbed as rapidly as formed. Since the
amount of amylolytic change is greatest not immediately
after eating but in the second or third hour of the digestive

1 My own attempts to repeal this experiment succeeded only once
on one out of four dogs.

2 Albbhtoni: Centralbl. f. Physiol., 1901, XV, p. 157.

3 Rohmanx and Nagano: Centralbl. f. Phywol., 1901, XV, p. 494.

i

286 PHYSIOLOGY OF ALIMENTATION.

period, ^ j« fomj that siaseh i-q n1gn mast rapidly, absorbed

during this ppriogV

After what has been said it becomes somewhat difficult
to explain the fate of starches which under experimental
conditions may be fed an animal in which the salivary and
pancreatic secretions are lacking, or patients in whom these
are insufficient in amount or poor in the proper enzymes.
It has been found that in dogs in which the pancreatic ducts
rhave beep ligaiad thai upwards of 50 pprppnt, of thp starches
fed cannot be recovered from the faeces. By what agencies
these starches are rendered absorbable is not known, for the
action of the gastric acid, the bacteria of the alimentary tract,
and the slight amylolytic activity attributed by some to the
intestinal juice seem insufficient.1

The question of the channels through which the carbo-
hydrates are distributed to the body after passing through
the epithelium of the alimentary tract seems to be settled
beyond question, v. Mering showed in 1877 that the absorbed
carbohydrates pass through the portal vpin, *r> fhp r"rej for
while under normal conditions the blood of this vessel con-
tains no more than about 0.2 percent dextrose, it may
contain twice this amount after^r carbohydrate meal. De-
t terminations of the sugar content of the lymph obtained from
I the thoracic duct showed that this fluid contained, both before
\ and after a meal of carbohydrates, a fa.irTvp.onsta.nt, pprppnt.
* (less than 0.2 percent) of sugar. T>"« shows that nn,oW
ordinary circumstances all the ca,rbohvdra.tps of thp food ,
leave the alimentary tract by wav of thp blood. When,
however, excessive amounts of carbohydrates are fed a
small portion of them may ■ pass over into the lymph-chan-
nels, as_ shown by Ginsberg's observations on rabbits and
dogs. Munk and Rosenstein's studies on a case of lymphatic
fistula in a human being fully confirm these observations.
It was found in this case, in which practically all the lymph

1 See Munk: Ergebnisse d. PhysioT., 1902, 1, lte Abth., p. 308.

ALIMENTARY TRACT AS AN ABSORPTIVE SYSTEM. 287

coming from the intestines was secreted externally, that
less than V-' gram of sugar was excreted through this channel
after a feeding <>[ ]()() grams Ol BJflJCfih ■'"1'1 M'";-'r in Other
words, not even 1 percent of the absorbed carbohydrates.1

9. The Absorption of Fat.— The means by which the
often enormous quantities of fat — 100 to 200 grams daily —
which the human being consumes are absorbed has for more
than half a century been the subject of most active research
and discussion. It is clear that in the fat of our food we ha vo
a substance which is, practically speaking, insoluble in \v:iter
and but little more soluble in protoplasm. In discussing
the problem of fat absorption we must, therefore, ask first
of all, Can fat be absorbed as such or is it first changed into a
soluble form?

Those authors who have held to the idea that fat is ab-
sorbed as fat have called attention to the fact that even
though it is insoluble, fat can be very finely divided and kept
suspended in water in a so-called emulsion. Not only do
many fats enter the alimentary tract in the form of such an
emulsion — for example, milk and raw yolk of eggs — but a
number of agents exist in the body which have the power of
emulsifying fats to a very high degree. As of first impor-
tance in this direction we must mention the bile, under the
influence of which any of the ordinary fats of the diet, such as
butter, the fat of meat, and olive-oil, may be speedily emulsi-
fied.

While these agents exist which can alter so markedly the
physkal state of the fats, there are others which are equally
potent in bringing about a chemical change in them. Of
first importance in this direction is lipase, a widely distributed
ferment which has the power of splitting fats into fatty acid
and alcohol. This chemical change which fats may suffer
in the body affects markedly the question of fal absorption,
for these products of fa I digestion are many of them soluble

1 See Mink: Ergebniss - d. Physiol., 1902, 1. Lte Abth., p. 309, where

references to the literature will U- found.

288 PHYSIOLOGY OF ALIMENTATION.

in water. Others are soluble in water if bile is present, and
some are soluble in protoplasm. If, therefore, it could be
shown that under the conditions which exist in the body it
is possible for all the fat of a fatty meal to be converted into
digestion products soluble in the body fluids, and this within
the time allowed for the absorption of such a meal under
physiological conditions, one of the great difficulties in the
way of believing that all fat is absorbed only in the form of
its soluble digestion products would be overcome. The ex-
tent to which the fat of a fatty meal is split into fatty acid and
alcohol during an ordinary period of digestion has been greatly
underrated by the majority of investigators. We know now
from the observations of Rachford x that in the hours making
up the ordinary period of pancreatic activity consequent
upon a meal ample time is allowed for the splitting of at
least the larger portion, and probably all of the fat consumed
in that meal.

Before entering further into the discussion of this question
let us ask first of all whether fat can be absorbed in the form
of an emulsion. If this question is answered in the affirma-
tive, then we have to ask, Is all the fat absorbed in this form,
or only a part of it, and how much? The mere question as
to whether fat can be absorbed in the form of an emulsion
must, perhaps, be answered in the affirmative. From a
physical standpoint the question is one which asks whether
substances having a high molecular weight can diffuse through
animal membranes. The physical experiment to settle this
question has been made by Eijkmann,2 who found that a
solution of glue poured upon an agar-agar plate will, if a
proper temperature be maintained, soon diffuse into the
agar-agar. In this case we have one colloid diffusing into
another. The physiological experiment to answer this ques-
tion has been made by Friedenthal,3 who fed colloidal so-

1 Rachford: Journal of Physiology, 1891, XII, p. 72.

2 Eijkmann: Centralbl. f. Bacterid., 1901, XXIX, p. 841.

3 Friedenthal: Archiv fur (Anat. und) Physiologie, 1902, p. 149.

ALIMENTARY TRACT AS AN ABSORPTIVE SYSTEM. 2R9

dium silicate to rabbits and young dogs and was able to re-
cover the salt from the urine1 in exceedingly small but never-
theless distinct amounts. This means, of course, that the
colloidal sodium silicate diffused through the gastro-intestinal
wall.

There is a difference, however, between asking whether fat
can pass as such through the intestinal mucous membrane
and whether under ordinary circumstances this is the way
in which it is absorbed. There seems to be little doubt that
even if fat can be absorbed as such, most of it passes through
the intestinal wall (and from tissue to tissue) in the form of
its soluble digestion products. As evidence of this we may
quote the experiments of Connstein.1 If the essential change
necessary for the absorption of fats lay in their conversion
into an emulsion in the animal body, then it would be reason-
able to expect that a fine emulsion of one fat should be
absorbed as rapidly as an emulsion of any other fat provided
it were equally finely divided. An emulsion of lanolin ought,
therefore, to be absorbed as readily as an emulsion of butter-
fat. As an actual matter of fact, Connstein found that when
he fed a dog with a lanolin emulsion in water 97 \ percent of
the entire amount fed could be recovered from the faeces.
The formation of an emulsion from the fat is, therefore, only
of secondary importance in the absorption of this foodstuff.
The real reason why lanolin is not absorbed in the above ex-
periment lies in the fact that it is acted upon only exceedingly
slowly by the fat-splitting enzymes of the digestive tract,
and hence is not converted into the absorbable products of
fat digestion.

The recognition by Kastle and Loevexiiart, and inde-
pendently of them by Hanriot, that the action of lipase is re-
versible, has altered entirely our conception of the mechanism
by which fat is absorbed from the intestinal tract.'-' Tin1 belief

'Connstein: Arcliiv fur (Anaf. u.) Physiol., ISO1.), p. 'M).
2 See p. 151, and Loevenhaht: American Journal of Physiology, 1902,
VI, p. 332,

290 PHYSIOLOGY OF ALIMENTATION.

of the older observers that fat is absorbed chiefly in the form
of an emulsion was based upon physiological experiments
and histological studies which showed that in ordinary diges-
tion the fat of the food is emulsified in. the lumen of the gut,
appears as droplets in the cells lining the gut, and in the same
form in the chyle, the fat-laden lymph which leaves the in-
testinal tract after a fatty meal. This conception was further
strengthened by the analytical results of physiological chem-
ists, who found but little fatty acid and alcohol (glycerine) in
any of these localities. The idea, therefore, that fat was ab-
sorbed in any other form than fat received little support, and
the formation of fatty acid and alcohol during digestion was
looked upon as of little importance.

As the following will show, fat is in all probability absorbed
only after it has first been split into fatty acid and alcohol
and never in the form of the original foodstuff. The observa-
tions of Rachford and the recognition of the reversible
action of lipase suffice entirely to explain the facts cited
above which have so long been quoted in support of the older
ideas of fat absorption.

Under normal circumstances fat is absorbed with great
rapidity from the intestinal lumen. From a physico-chemical
standpoint alone, therefore, it appears very unlikely that fat
enters the cells of the intestinal mucosa as such, for fat has
only slight powers of diffusion, especially into solvents made
up chiefly of water, such as protoplasm. To overcome this
argument the intestinal epithelium has been endowed with
powers of amoeboid motion and (hypothetical) tubules sur-
rounded by contractile protoplasm. Even were its entrance
into the intestinal mucosa explained in this way, its exit into
the lacteals and from here into the various tissues of the body
would yet have to be accounted for. The same explanation
could evidently not hold in all these cases of absorption. The
belief, on the other hand, that fat enters and leaves the intesti-
nal mucosa only in the form of its cleavage products — in fact,
enters and leaves all tissues in this form — meets with no such

ALIMENTARY TRACT AS AN ABSORPTH E SYSTEM. 291

objections. The cleavage products of Eat are readily soluble
in the fluids and tissues of the body and diffuse with great
rapidity.

The exact form in which the cleavage products are absorbed
cannot as yet be looked upon as settled definitely. For the
sake of simplicity we will adopt Munk and Loevenhaht's
opinion that fat is absorbed as fatty acid and alcohol. This
is probably correct, though it is at variance with the belief
of certain other investigators that the fatty acid unites with
the alkalies of the body and forms soaps. Whichever may
ultimately have to be adopted will not alter the fundamental
principles of the mechanism of fat absorption. Since certain
of the fatty acids are practically insoluble in water, and
since solubility is so important a factor in absorption, it is
well to bear in mind Moore and Rockwood's experiments,
which show that the insoluble fatty acids become freely soluble
in the presence of bile.

It is well to impress anew upon the reader that lipase,
which we ordinarily think of as a constituent of the pan-
creas and the pancreatic juice only, is really very widely
distributed throughout the body, where it occurs in different
amounts in practically every tissue and fluid. Of immediate
interest to us is the fact that lipase occurs in the mucosa of
the intestine as also in the lymphatic glands, lymph, and the
blood.

Bearing in mind the facts stated above regarding lipase,
its action and its distribution, let us trace the chemical changes
which follow the ingestion of a fat. This substance is not
acted upon in the mouth or oesophagus. As lipase is found
in the gastric juice and gastric mucosa it is possible that
some digestion may occur in this viscus. This will occur
especially if the meal has been one which calls forth a secre-
tion of but little hydrochloric acid or if the digestion occurs
in a stomach which through pathological change is secreting
a deficient amount of this acid. The activity of the lipase
under these circumstances is not interfered with. It is

292 PHYSIOLOGY OF ALIMENTATION

entirely possible that the appearance of butyric and other
fatty acids in diseases of the stomach is attributable in part
at least to the activity of the lipase normally present here.

But even if under normal circumstances little or no diges-
tion of fats occurs in the stomach, active digestion of this
food begins as soon as the gastric contents are neutralized
in the duodenum and have poured out upon them the pan-
creatic juice and the bile. The function of the latter we will
ignore for the present. Let us ask first of all how much of
the fat will be split under the influence of the pancreatic juice
as the mixture of the two moves down the intestine. It is
clear that if the intestine were replaced by a glass tube, by
no means all of the fat would be split, but only a portion of
it, or to put it more technically, fat would undergo cleavage
until an equilibrium had been established between this sub-
stance on the one hand and fatty acid and alcohol on the
other. In other words, we recognize here again an equa-
tion similar to the one given on page 107:

Fat ±± Fatty acid + Alcohol.

In the animal body conditions are somewhat different than
in a glass tube. While in a glass tube the products of the
cleavage accumulate, this does not occur in the intestine, for
here the fatty acid and alcohol diffuse into the intestinal
mucosa as soon as formed. Evidently, therefore, the state
of equilibrium outlined above never comes to pass in the in-
testine, and the cleavage of the fat continues until all has
been split, in other words, all has been absorbed. This really
occurs, for under normal circumstances no fat, or practically
none, is found in the faeces.

Let us see now what becomes of the fatty acid and alcohol
which have diffused into the lining cells of the intestine. At
the beginning of a meal these cells contain no fat, but they
do contain lipase. As the fatty acid and alcohol diffuse
into them evidently the reverse of what occurred in the lumen

ALIMENTARY TRACT A3 AN ABSORPTIVE SYSTEM. 293

of the gut must happen here, for since the action of lipase
is reversible it must synthesize fat from the products of the
fat digestion which is going on in the lumen of the intestine.
In other words,

Fatty acid + Alcohol <=± Fat.

It is this synthesis of fat in the epithelium of the gut which
gives rise to the appearance of fat droplets in this locality,
and which the older observers looked upon as evidence sup-
porting the idea that fat is absorbed as an emulsion.

We have yet to explain the transport of the fat into the
lymph-channels. The fatty acid and alcohol which diffuse
into the cells lining the intestine do not stop here but pass
on into the lymph current beyond. At the beginning of a
digestion period this is also free from fat, but it contains lipase.
Evidently the same play must occur in this liquid tissue which
we saw take place in the cells lining the intestine. Under
the influence of the lipase the fatty acid and alcohol are syn-
thesized into fat, and it is this fat which evidences itself in
the droplets found in the lymph returning from the intestine.
That we are dealing with a chemical equilibrium in this case
also is shown by the fact that the lymph always shows the
presence of free fatty acid accompanying the fat.

In order to get a conception of the process of fat absorp-
tion as a whole, we need only to imagine these different proc-
esses of analysis, diffusion, and synthesis going on simul-
taneously and side by side. We are in a position now to rec-
ognize the unimportant role played by the fat droplets which
appear in the epithelial cells of the intestine. They are
evidently transitory creations, which exist only as long as
fatty acid and alcohol are diffusing through these cells. When
the last remnants of fatty acid and alcohol diffuse out of the
cells into the lymph stream (ho fat in the cells can no longer
maintain itself, and the lipase which before hastened its
synthesis now hastens its analysis until i! too has disappeared
as fatty acid and alcohol into the lymph stream. This leaves

294 PHYSIOLOGY OF ALIMENTATION.

the cells once more in the empty condition in which they
were found at the beginning of the digestion period.

Under the influence of the lipase they contain, the tissues
of the body also store fat when it is plentiful in the food and
give it up during starvation in the same manner as the epithe-
lial cells of the intestinal mucosa ; but a discussion of this
problem is beyond the limits of our subject. One more fact
is of interest in support of the ideas of fat absorption ad-
vanced above. We would expect from chemical considera-
tions alone that if a certain fat is digested by lipase, the
products of its digestion should, when synthesized under the
influence of the same ferment, yield the original fat, and
that this ought to hold when different kinds of fat are con-
sumed by animals. Not only were Munk and Rosenstein
able to isolate from the lymph obtained from their patient
with a lymphatic fistula an oily fat when olive-oil was fed,
and a tallow-like fat when mutton-tallow was administered,
but Rosenfeld x has been able to show niore recently that if
one dog is fed cocoa-butter and another mutton-tallow the
fats deposited in each case correspond to those ingested.
Goldfish and carp, moreover, deposit mutton-tallow when
this is fed to them.

Unlike the absorption of the carbohydrates and the pro-
teins, which leave the alimentary tract with the blood stream,
the fats leave the absorptive mucous membrane almost en-
tirely by way of the lymph. Very shortly after a fatty meal
the lymph leaving the intestine assumes a milky appearance,
owing to the exceedingly fine droplets of fat contained in it,
and at the height of absorption may contain from 3 to 8 per-
cent of fat. The lymph returning from the intestine and
thus laden with fat is known as chyle. Munk and Rosen-
stein found that more than 60 percent of the fat consumed
by their patient with a lymphatic fistula could be recovered
from the lymph within the first twelve hours after feeding.

1 Rosenfeld: Verhandlungen d. XVII. Congress f. innere Medicin,
1899, p. 503.

ALIMENTARY TRACT AS AN ABSORPTIVE SYSTEM. 295

Some fat seems, however, to be carried from the intestine
by way of the blood-vessels, and when the thoracic duel has
been ligated the amount carried in this way is much increased.
Munk and Friedenthal found that the fat in the blood
may under circumstances rise to six times the normal amount
when the thoracic duct is occluded. A thick layer of fat
forms upon the blood collected from a vein even though
the entire amount of fat absorbed from the intestine may
be less than half that absorbed when the thoracic duct is
open.

The total amount of fat absorbed is dependent upon the
kind of fat fed an animal. We know from Munk and
Muller's observations that fats having a low melting-point
are more perfectly absorbed than those having a higher one.
97.7 percent of the olive-oil fed an animal is absorbed.
97.5 percent of fats melting between 25° and 34° C. (goose-
and pork-fat), 90 to 92.5 percent of fats melting between 49°
and 51° C. (mutton- tallow) , and only 89.4 percent of a mix-
ture of stearin and almond-oil melting at 55° C. are absorbed.
Of pure stearin, which does not melt until 60° C. is reached,
only 9 to 14 percent is absorbed.1 When a mixture of fats
having different melting-points is fed, those having the lower
melting-points are absorbed more completely than those
having the higher. Fat is also more perfectly absorbed
when it is free in the form of butter or lard than when it is
enclosed in cells, as in fat meat or bacon. Under these cir-
cumstances the digestive juices must first dissolve the walls
of the cells.

The velocity with which different fats are absorbed is also
determined in large part by their melting-points. .Mink
and Rosenstein found that the lymph obtained from their
patient with a lymphatic fistula became milky in appear-
ance two hours after feeding a mixture of olive-oil containing
6 percent oleic acid, and in the fifth hour after feeding con-

1 Munk: Ergebnisse d. Physiol., 1902, I, Lie Al.th., p. 323.

296 PHYSIOLOGY OF ALIMENTATION.

tained a maximum of 4^ percent fat. When mutton-tallow
was fed a maximum of 3.8 percent fat in the lymph was not
reached until the seventh or eighth hour. The consump-
tion of a fat melting at 53° C. did not lead to more than a
milkiness of the lymph in the fifth to the sixth hour (only
0.7 percent fat), which continued with a progressive fall in
the percentage of "fat until the thirteenth hour.

This is, perhaps, the best place at which to discuss the
importance of the bile and the pancreas in the absorption
of fats. This question is of clinical moment, for a de-
ficient secretion or total lack of bile or pancreatic juice is
encountered in a number of pathological conditions. All
authors are agreed that when experimentally or through
pathological states the bile is prevented from entering the
duodenum the fats are much less perfectly absorbed than
under normal circumstances. This fact was recognized half a
century ago by Bidder and Schmidt, and has since then been
corroborated and amplified by a score of investigators. The
exact amount of fat absorbed by men or animals when no
bile enters the intestine is subject to great variation, so that
it is not surprising that the figures of different students of
the question vary greatly. It is ordinarily stated that less
than half of the fat which under normal circumstances
readily disappears from the alimentary tract is absorbed
when no bile is present. The highest figures ever attained
are the disappearance of 70 percent of the fat against 95
percent in normal animals as determined by analysis of the
faeces. The character of the consumed fat plays an im-
portant role. A fat with a low melting-point is more readily
absorbed than one with a higher one, just as under normal
circumstances.1 Munk found that the absorption of mutton-
tallow, for example, was interfered with twice as much as
the absorption of pork-fat. A further interesting fact which
at present still lacks an explanation is that the proportion

1 Munk: Ergebnisse d. Physiol., 1902, 1, lte Abth., p. 324.

ALIMENTARY TRACT AS AN ABSORPTIVE SYSTEM. 297

of fatty acids to fat in the faeces is much lusher when no bile
is present than when it is. Normally, two-thirds to seven-
tenths of the fatty substances present in the fasces are fatty
acids, while in the absence of bile eight-tenths to nine-tenths
are fatty acids, the rest neutral fat. It was formerly believed
that this could be explained through Moore and Rock-
wood's observation that the fatty acids are more soluble in
the presence of bile and hence are more readily absorbed
when this secretion is present, but Munk has shown that
the reverse is true by finding that fatty acids are more readily
absorbed than neutral fats in the absence of bile.

The many observations at hand on the effect of removal
of the pancreas or ligation of its duct all agree that the absorp-
tion of fat is much hampered by such procedures. Vastly
different figures are, however, found in the literature to
illustrate the extent to which the absorption of fats is de-
creased. When not in the form of an emulsion fats are
absorbed in very slight measure when the pancreatic secretion
is entirely lacking. Hedon and Ville state that 10 percent
of an olive-oil feeding may be absorbed and 22 percent of the
fat of milk. Minkowski and Abelmann give even higher
figures for the absorption of oil in the form of an emulsion,
28 to 53 percent of milk-fat.1 That any fat at all should be
absorbed in the absence of a pancreatic secretion was long
regarded as a remarkable fact. This can no longer be con-
sidered a mystery since we have become acquainted with
the almost universal distribution of lipase in the tissues and
fluids of the body. The mucous membrane of the small
intestine contains this ferment, and no doubt some is found
in the secretions of this viscus. To the ferment present from
these sources must be attributed whatever digestion and
absorption of fat we may encounter in an animal deprived
of its pancreatic secretion. With the limited amount of
lipase present under these circumstances it cannot seem

1 Quoted from Munk, 1. c, p. 325.

298 PHYSIOLOGY OF ALIMENTATION.

strange that an emulsion of a fat with its larger surface should
be better absorbed than the same fat when not previously
emulsified. It is self-evident that with a deficient amount
of lipase the conditions normally provided for the rapid
production of an emulsion from the fat of the food are much
impaired.

The destruction of lipase through the gastric secretions
has already been pointed out. When fed in the form of raw
chopped pancreas some seems, however, to reach the small
intestine in an uninjured state. It is a fact of clinical im-
portance, therefore, that Sandmeyer has found that the ab-
sorption of fats in dogs deprived of their pancreas is much
increased through the feeding of raw minced pancreas.

CHAPTER XVII.

THE ALIMENTARY TRACT AS AN ABSORPTIVE SYSTEM.

{Concluded).

io. The Absorption of Proteins. — Since the proteins, un-
like the salts and water, and like the fats and certain carbo-
hydrates, suffer profound changes in their passage through
the alimentary tract, the question arises first, of all, Are the
proteins absorbed entirely or in part as such, or do they first
suffer a decomposition into simpler substances before they
pass through the absorbing wall of the intestinal tract?

Physico-chemical reasons indicate that the proteins are not
absorbed as such, or only in very small amounts, for belong-
ing as they do to the general class of the colloids they are not
able, practically speaking, to diffuse through a colloidal mem-
brane such as the alimentary tract presents. Experimental
facts agree entirely with this reasoning. As Friedlander's l
experiments have shown, acid-albumin does not disappear
when introduced into a well-washed loop of intestine. In
opposition to this are the experimental results of most other
observers. Brucke, Y<>it, Bauer, Czerny, Latschenberger,
Neumeister, and Mink all believe that no inconsiderable
amounts of such substances as egg-albumin, myosin, blood-
serum, and acid-albumin can be absorbed as such from care-
fully cleaned loops of intestine in I he course of one to four
hours. The disappearance of even 10 or 20 percenl of the
protein introduced in this way does not prove necessarily
thai it was absorbed in the " native " state. The fact that the

1 Fkikim.animj;, Zeitschr. f. Biol., 1896 XXXIII, ]>. 274.

299

300 PHYSIOLOGY OF ALIMENTATION.

amount of peptones in the blood leaving the intestines is not
increased is an inconclusive argument, for they are not in-
creased to any marked degree even under conditions when
we know that the protein is being absorbed in the form of
the soluble digestion products. From our knowledge of the
almost universal distribution of proteolytic enzymes through-
out the tissues and fluids of the animal body and their great
activity in the living organism, it does not seem too hazardous
to believe that even that portion of a protein solution which
is believed to be absorbed in the ' 'native " state is in reality
absorbed in the form of peptones, or still more probably in
the form of the simple crystalline products of proteolytic
activity.

But even if we allow that proteins may be absorbed as
such the amount that passes through the wall of the alimen-
tary tract in this form must be small. Just how small cannot,
of course, be said, but the knowledge that adequate means
exist in the body to split all the protein of an ordinary meal
in the course of a few hours, and that the diffusion velocity
of even such complex substances as the peptones is several
times that of the proteins from which they are derived, in-
dicates that under ordinary circumstances only a small
fraction, if any at all, of the protein of an ordinary meal is
absorbed in an unchanged state.

If protein is not absorbed as such, then in which of the
various forms into which it is changed under the influence
of the proteolytic ferments is it absorbed? This is a ques-
tion which it is exceedingly difficult to answer, for the multi-
tude of experiments that have been performed by many
different investigators have not in any sense yielded results
which are either entirely satisfactory or capable of only one
interpretation. The burden of experimental evidence seems
to indicate, however, that most, if not all, protein is absorbed
in the form of the very simple crystalline products of pro-
teolysis with which we became acquainted in the discussion
of acid- and alkali-pro teinase (pepsin and trypsin), and pro-

alimentary tract as an absorptive system. 301

tease (erepsin). The arguments which point in this direction
are the following: The proteoses still stand close to the -so-
called "typical" colloids, and their absorption as such is
open to the same objections from a physico-chemical stand-
point which were raised against the albumins from which
they are derived. The same holds true of many of the
peptones (in Kuhne's sense), though some of them approxi-
mate the crystalloids in their physical behavior. In any
case, both classes of substances are readily decomposed under
the conditions existing in the body. As agencies bringing
about such a decomposition we have the already-mentioned
proteolytic ferments. Recent work indicates that acid-pro-
tcinase approximates at least qualitatively the proteolytic
activity of alkali-proteinase, and in protease we have a newly
discovered ferment which seems to be most energetic in break-
ing down proteoses and peptones into the simple crystalline
products which have long been considered characteristic of
the activity of alkali-proteinase (trypsin). Finally, if the
proteins are really broken up into simple crystalline sub-
stances before being absorbed it ought to be possible to find
them in the alimentary contents. This has been done by
Kutscher and Seemann, who succeeded in obtaining leucin,
tyrosin, and lysin from the intestinal contents of the dog.
The amount which they obtained was not large, and this is
often taken as an argument to show that not all or even a
large part of the protein of a meal is split as far as the mono-
and diamino-acids. The objection is perhaps scarcely a
valid one, for not only are these substances readily diffusible
so that a collection of a considerable amount is rendered
well-nigh impossible, but all the proteolytic change does not
occur in the lumen of the gut; part takes place in the wall
of the intestine, where protease (erepsin) is present in large
amounts and into which :i1 least some of the peptones diffuse
easily. All these facts seem to indicate, therefore, thai the
proteins are absorbed, nl leasl in the main, in (he form of
the simplest digestion products.

302 PHYSIOLOGY OF ALIMENTATION.

Through what channel or channels are the proteins carried
away from the alimentary tract? It has been found that
the same holds true here as in the case of the carbohydrates.
Under ordinary circumstances practically all the protein of
a meal passes from the alimentary tract through the blood-
vessels and only when excessive amounts are fed does a small
percent pass over into the lymphatic circulation. Schmidt-
Mulheim showed this to be true when he found that the ab-
sorption of the proteins from the alimentary tract is not
impeded when the main lymphatic channels coming from
the alimentary tract are tied off. Munk and Rosenstein's l
studies on a patient with a lymphatic fistula through which
most of the visceral lymph was poured out externally show
this in a still better way. When 80 to 103 grams of lean meat
were fed this patient at a single meal (which more than
covers the entire amount of protein consumed by the ordi-
nary individual in a day) it was found that neither the total
amount of lymph nor the percent of nitrogen in the lymph
was markedly increased during the twelve hours following
the meal. L. B. Mendel 2 has come to similar conclusions
from his experiments on dogs. Even when excessive amounts
of protein are fed scarcely more than one-fifteenth of the
whole amount that is absorbed passes from the alimentary
tract through the lymphatics.

The relative importance of the stomach and of the intestine
with its attached pancreas as organs concerned in the diges-
tion and absorption of the proteins is somewhat difficult to
determine, and the data we have at our disposal vary greatly.
Since Czerny, in 1878, removed the entire stomach of a dog
and kept him in good health for six years afterward (when he
was killed for study) no one has seriously questioned the
statement that the stomach is not essential to good health,
provided only a proper diet be observed. Ludwig and Ogata

'Munk and Rosenstein: Ergebnisse d. Physiologie, 1902, 1, lte
Abth... p. 312.

2 L. B. Mendel: American Jour, of Physiol., 1899, II, p. 137.

ALIMENTARY TRACT AS AN ABSORPTIVE SYSTEM. 303

were able to show that the nitrogenous excretion of dogs
could be covered entirely through the nitrogen obtained
from finely minced meat, eggs, h<\. introduced directly into
the duodenum through a fistula, and more recently a number
of operations carried out on human beings in which all or
nearly all the stomach lias been removed have shown that
absence of this organ does not jeopardize life. • The pan-
creas with the small intestine is able to take care of all the
protein necessary for the life of the individual. For reasons
which have already been pointed out, such patients do best
on sterile food, for the gastric juice is no longer present to
reduce the number of bacteria consumed with the ordinary
food; and since an organ is no longer present which acts as a
reservoir for the food and gives small amounts periodically
to the intestine, repeated feedings only can be well tolerated.
Since the acid of the gastric juice is best able of all the ali-
mentary secretions to act upon the connective tissues, these
appear in the fseces after the stomach is gone.

The experiments which have been made to determine the
importance of the stomach as an absorptive organ for the
proteins are not free from criticism. They seem to indicate,
however, that a small percent, perhaps, of the total amount
of the protein in an ordinary meal may be absorbed by the
gastric mucous membrane. As the chief absorptive organ
of the proteins we must regard the small intestine, more
especially the upper half. This absorptive power decreases
apparently from above downwards, reaching a very low
grade in the large intestine.

According to most observers the pancreas plays a much
heavier role than the stomach in the digestion of the
proteins. To till extirpation of the pancreas is fatal, for this
is followed by a diabetes which ends the life of its vic-
tim in a few days. For this reason it, becomes necessary in
experiments on the digestive functions of the pancreas to
limit oneself to occlusion of the pancreatic duct or duct-- by
means of ligatures, or to only partial excision of the pancr

304 PHYSIOLOGY OF ALIMENTATION.

or total excision with transplantation of a portion of the
organ to some other part of the body. These various pro-
cedures have been adopted by different investigators. The
results obtained vary greatly. All seem to agree, however,
fhat the digestion and absorption of proteins are interfered
with markedly when the pancreatic juice no longer pours
into the duodenum. This is not surprising when it is remem-
bered how well protein digestion may go on after removal
of the stomach. Generally speaking, less than half the pro-
tein of an ordinary meal is digested when the pancreas is
gone. Harley found only 18 percent digested after removal
of the pancreas, though Deucher found 80 percent utilized
after complete occlusion of the pancreatic duct.1 The pro-
teolytic activity must evidently be sought in these cases in
the secretion of the stomach, augmented by those found in
the secretions and mucous membrane of the small intestine.

What, now, is the fate of the protein which disappears
from the lumen of the alimentary tract? Of fundamental
importance is the fact that even after a meal rich in proteins
neither peptones nor proteoses appear in either the blood or
the lymph. This has been shown to be true in various ways :
Direct analysis of the blood leaving the intestine points in
this direction. Furthermore, peptones injected directly into
the blood are excreted through the kidneys, and normally
no peptones can be found in the urine, even after a very
heavy protein meal. The peptones lower the blood pressure
when injected into the general circulation, yet a lowered
blood pressure is never observed after the consumption of
large amounts of protein, or even after the introduction of
large amounts of peptone into the alimentary tract. All this
indicates clearly that peptones do not get into the blood or
lymph (at least in sufficient amounts to be recognized by
the analytical means ordinarily employed). Nor do peptones
and proteoses in the blood issuing immediately from the in-

'SeeMraK: I.e., p. 316.

ALIMENTARY TRACT AS AN ABSORPTIVE SYSTEM. 305

testinc appear to be caught and held by some organ, such as
the liver or spleen, before passing over into the general cir-
culation. This has been shown by comparative analyses of
the blood obtained from the portal vein, for example, and
(hat obtained from a large artery, as well as by the experi-
ments already cited.

What, then, does become of the proteins which enter the
alimentary tract? It is clear that if they disappear from the
lumen of the intestine and cannot be discovered in the blood
leaving the alimentary tract as proteoses and peptones they
must exist here in some other form. In what form cannot
be easily said, though there are two possibilities, either or
both of which may be correct, and both of which have ex-
perimental foundation.

The first of these is that the proteins, be these absorbed in
whatever way we may consider the correct one, are recon-
structed in their passage through the epithelium of the
stomach or intestine into complex albumins and globu-
lins which we are unable to distinguish from those found
normally in the blood. This means that if we believe all
the protein of a meal to be absorbed in the form of Kuhne's
peptones, or perhaps in the form of mono- and diamino-
acids, that these are reconverted into complex albumins in
passing through the alimentary wall.

The experiments of Abderhalden and Samuely l are of
great interest in this connection. These show that the com-
position of the blood, so far as its protein constituents are
concerned, is apparently entirely independent of the char-
acter of the proteins consumed by the individual. Analysis
of six litres of blood removed from the veins of a horse showed
that it contained protein bodies which yielded after hydrol-
ysis:

Tyrosin 2 . 43 percent

Glutamic acid 8.85 "

1 Audekhaldkn and SaM^ELY: Zdtsvhr. 1". physiol, (.'hem., 10"),
XL VI, p. 193.

306 PHYSIOLOGY OF ALIMENTATION.

After starvation for a week, in order to free the alimentary
tract from food, analysis of another six litres of blood yielded
practically the same results :

Tyrosin 2 . 60 percent

Glutamic acid 8.20 "

The horse was now fed a protein (gliadin) which is much
richer in glutamic acid than blood serum and contains about
the same percent of tyrosin. Even when 1500 to 2500 grams
of the protein were fed analysis of the blood showed prac-
tically no variation in its composition. The following table
gives the results of three experiments:

1500 gms. 1500 gms. 2500 gms.
Percent. Percent. Percent.

Tyrosin ...2.24 2.52 2.48

Glutamic acid 7.88 8.25 8.00

It seems, therefore, as though an actual synthesis of pro-
tein occurs in the wall of the intestine itself. From the
most varied kinds of protein consumed by an animal are con-
structed first of all the serum albumin and serum globulin found
in the blood-serum of that animal, and from this serum, so
constant in its composition, the different cells of the body each
take the substances necessary for their purposes. Indirectly
we find in these considerations support for the idea that the
proteins are absorbed from the alimentary tract only in the
form of the simple digestion products, for these can most
readily be joined chemically to produce the protein bodies
characteristic of the animal under consideration.

As Abderhalden x has well pointed out, these conceptions
place the functions of the alimentary tract and its enzymes in
an entirely new light. They together guarantee a proper met-
abolism of the body as a whole. The ferments through their
action on the various foodstuffs break these up into their
elements, which are the same even when derived from the

1 Abderhalden: Lehrbuch d. physiol. Chem., Berlin, 1906, p. 232.

ALIMENTARY TRACT AS AN ABSORPTH E SYSTEM. 307

most varied parent bodies. The alimentary trail then
synthesizes from these elements the complex substances
found in the blood. In disturbances in general metabolism
involving the alimentary tract it is not so much the impaired
absorption that is so important as the impaired assimila-
tion. That this synthesis of protein plays an important role
in the metabolism of the animal has been shown very strik-
ingly by Abderhalden and Roxa.1 These authors were able
to keep animals in nitrogenous equilibrium by feeding them,
in addition to an ordinary mixture of fats and carbohydrates,
casein which had been previously digested through alkali-
proteinase, so that 80 to 85 percent of it consisted of amino-
acids mixed with simple polypeptides, the remaining 15 to 20
percent of more complex polypeptides, but not sufficiently
so to give a biuret reaction.

As agencies capable of such a reconstruction of the albu-
min molecule have been mentioned the chemical forces of
the epithelial cells themselves and the activities of Julia
Biuxck's micrococcus restituens. That a microorganism living
upon the surface of the alimentary mucous membrane should
be of any importance to its host by being able to reconstruct
from the products of proteolysis the protein itself (which
would again have to be broken up before it could pass through
the epithelial cells in any amount) is, no doubt, too improb-
able to need serious consideration. There is much more likeli-
hood that the chemical forces residing in the epithelial cells
are capable of reconstructing albumins from the products
of proteolysis. Elsewhere2 experiments have been dis-
cussed which seem to indicate that the activity of the pro-
teolytic ferments is reversible. Were this true, then the
synthesis of albumins within the epithelial cells lining the
alimentary tract, in a way entirely analogous to the syn-
thesis of fat in this locality under the influence of lipase,

1 Abdi rhai m« and Rona: Zeitschr. f. physiol. Chem., 1004, XL1I,
p. 528; ibid., 1005, XLIV, p. 10S.

2 See p. 140.

308 PHYSIOLOGY OF ALIMENTATION.

might readily be explained. The presence of such ferments
as alkali-proteinase (trypsin) has been demonstrated not
only in these cells but in practically every cell and fluid of
the body.

A second reason why the products of proteolysis — prote-
oses, peptones, or amino-acids — do not appear in the blood
leaving the intestine may reside in the fact that they are in
their passage through the intestinal wall broken into yet
simpler substances. The proteinase and protease present
in the cells of the mucosa may well continue their work until
none of the higher polypeptides are left. But, even if all the
protein is first split into the simple mono- and diamino-acids
before passing into the blood, as seems to be the case, all these
acids need not necessarily go to build up albumins and glob-
ulins once more. They may be broken into yet simpler
substances. There exist in the mucous membrane of the
alimentary tract and in various organs in the body ferments
which are capable of bringing about such a destruction of
mono- and diamino-acids. With one such ferment we are
acquainted, through Kossel and Dakin's work on arginase,
which is a ferment capable of acting upon arginin and split-
ting this into urea and ornithin. The discovery of this fer-
ment, as also the well-known fact that the excretion of urea
in the urine reaches its maximum shortly after the consump-
tion of a protein meal, seems to indicate that a portion, at
least, of the albuminous bodies which constitute our food are
rapidly broken up into the ultimate products of protein met-
abolism. Apparently, therefore, a part of the protein we ab-
sorb goes to maintain the proportion of albumin and globulin
found in the blood, and so is distributed to the cells and tissues
of the body, while another serves as a source of energy and
leaves the body in the form of urea.

This is perhaps the best place in which to discuss the
physiological importance of protease (erepsin) as a digestive
enzyme, and of importance, in consequence, in the absorption
of the proteins, It is evident that from the nature of its action

ALIMENTARY TRACT AS AN M'.SORPTIVE SYSTEM. 309

alone it might well play a rule not inferior to thai of acid-or
alkali-proteinase (pepsin or trypsin). Not only does protease
act on casein directly, but it is able to bring about the split-
ting of proteoses and peptones as energetically and as rapidly
as either acid- or alkali-proteinase. In fact, it need not
surprise us if in the near future we discover that some of the
cleavages of protein which we have thus far attributed to
alkali-proteinase are in reality brought about through the
protease existing beside the proteinase as an impurity.

Protease is found not only in the secretions of the small
intestine but also in the cells of the intestinal mucosa. Since
much more is found in the latter location than in the former,
it may well be concluded that the protease within the cells
is of greater physiological importance than that contained
in the secretions. Self-apparent also is the fact that the
power of diffusion possessed by the proteoses in part, by the
peptones (in Kuhne's sense) in much larger part, plays an
important role in rendering the protease found in the cells
an active agent in the demolition of the protein molecule.

The following experiment 1 illustrates the rapidity with
which a peptone solution disappears from the intestine.
A loop of intestine 50 cm. long is carefully taken out of the
abdominal cavity of a dog and after being ligatured at both
ends is opened and well washed. 39 c.c. of a peptone solution
containing 0.49 gm. nitrogen are introduced into the intestine
and the loop replaced in the abdominal cavity. At the end
of an hour the loop is again taken out and the amount of
unabsorbed peptone solution determined. It is found that
0.29G gm. nitrogen has been absorbed, in other words, over
60 percent.

When the 95 cm. of intestine which were not used in this
experiment are taken into consideration, simple calculation
shows that this dog would have boon able to absorb from its
entire small intestine more than 0.8 gm. nitrogen per hour.

'Coii.nheim: Zcitsclir. f. physiol. Chemie, L902, XXXVI, p. 13,

310 PHYSIOLOGY OF ALIMENTATION.

This figure, which is by no means the highest that might be
given for experiments of this sort, indicates how rapidly
peptones disappear from the small intestine, especially when
it is added that at this rate a dog could absorb in one hour
nearly enough nitrogenous material to suffice for its daily
existence.

It remains for us to show that this rapid absorption of
peptones is determined by the action of protease upon them,
whereby they are dissociated into the very diffusible crystal-
line digestion-products which have been enumerated above;
and that this dissociation is not brought about by such a
ferment as alkali-pro teinase (trypsin). While under ordi-
nary circumstances both alkali- and acicl-proteinase are
active in bringing about the dissociation of the protein which
we take in with our food, under the experimental condi-
tions outlined above this is not the case, for a well-washed
loop of intestine contains no alkali-pro teinase (trypsin), or
at best only very little. This has been repeatedly shown
by experiments in which proteins, such as fibrin, are intro-
duced directly into the small intestine, when it has been
found that they disappear very slowly (in days or even
weeks).

CHAPTER XVIII.
THE ALIMENTARY TRACT AS AN EXCRETORY SYSTEM.

i. General Clinical and Experimental Considerations. —

Practical medicine has for a long time recognized empirically
the function of the alimentary tract as an organ of excretion.
As an example we need only cite the practice of purgation
in cases of renal disease, in which the effort is made to carry
off the poisonous metabolic products of the body through
the intestinal tract. The beneficial effects following this
therapeutic procedure are illustrated in the clinical experi-
ences of every day.

The scientific basis of this practice has not as yet been
definitely established through experiment. It is true that
there exist a large number of isolated facts, which show that
various poisons, no matter how introduced into the living
organism, are eliminated through the alimentary tract. Every
physician is acquainted with the elimination of the iodides
through the salivary glands after introduction of these salts
into the stomach; l with the elimination of arsenic and mor-
phin2 through the stomach, even when these substances
do not enter the organism through the intestinal tract,
and with the excretion of iron compounds through the small
intestine. Mendel and Thacher3 have recently collected a

1 Penzoldt and Faber: Berliner klin. Wochenschr., 1SS2, XIX,
p. 363.

2 Kunkel: Handbuch d. Toxicologic, 1901, p. 54.

3 Mendel and Thacher: American Journal of Physiology, 1904,
XI, p. 5.

311

312 PHYSIOLOGY OF ALIMENTATION.

large number of instances illustrating the fact that various
organic and inorganic substances are eliminated through the
alimentary tract. For the most part, however, quantitative
determinations, showing the amounts of the various sub-
stances eliminated in this way and the amounts cast off
through the other emunctories of the body, for instance, the
kidneys and skin, have not been made in these earlier experi-
mental studies.

With the especial purpose of determining the relative im-
portance of the kidneys and alimentary tract as organs of
excretion for certain of the inorganic compounds, Mendel and
his pupils, Hanford and Thacher, have taken up this
problem.1

Mendel and Thacher used strontium (in the form of stron-
tium acetate) in their experimental studies, as this is an ele-
ment which does not occur normally in the ordinary labora-
tory animals, and hence can be readily recognized in the
different tissues spectroscopically. As the experiments were
designed to determine the function of the alimentary tract
as an excretory organ the salt could not be given by mouth.
A four percent solution of strontium acetate was in conse-
quence injected subcutaneously with all aseptic precautions, or
at times intraperitoneally or intravenously. The animals were
kept in metallic cages and the urine and faeces collected
separately. A series of experiments performed on dogs, cats,
and rabbits yielded the following interesting results.

Strontium is eliminated only to a small extent through the
kidneys, even when this element is introduced in the form of
a salt directly into the circulation. The excretion in the
urine begins shortly after the injection and usually ceases
within twenty-four hours. By far the larger portion of the
strontium is excreted through the fseces, and it is immaterial
how the element has been given. The place of excretion is

1 Hanford: American Journal of Physiology, 1903, IX, p. 235;
Mendel and Thacher: ibid., 1904, XI, p. 7,

ALIMENTARY TRACT AS AN EXCRETORY SYSTEM. 313

apparently limited to the region of the alimentary tract be-
yond the stomach.

The following experiments will serve to illustrate the fore-
going. As strontium tends to be stored in certain tissues of
the body and is only eliminated slowly, the dejecta of the
animals experimented upon have to be studied for several
days. A dog weighing 6 kilos received a number of subcu-
taneous strontium acetate injections, the total amount of
strontium injected being 0.543 gm. The urine and faeces
were collected separately for 21 days. The total urine con-
tained an unweighable trace of strontium. The total fseces
contained 0.0998 gm. of this element.

At times, however, a much larger percentage of the injected
strontium can be recovered. A dog weighing 14 kilos was
given 0.28 gm. strontium (in the form of the acetate) sub-
cutaneously. At no time for 17 days subsequently could
strontium be detected in the urine. From the faeces 0.237
gm. were recovered during this period.1

In a series of experiments which Professor Mendel 2 has
communicated to me by letter, he has been able to show that
barium behaves not unlike strontium. If barium chloride is
introduced into the body even in other ways than through
the mouth, it is eliminated almost exclusively by the intes-
tinal tract. After the first twenty-four or forty-eight hours
the urine shows no signs of containing the element barium,
even though the faeces contain the substance for days after-
ward. Barium tends to be stored in the body even more
readily than strontium and so is eliminated more slowly.

Rubidium belongs in the class with sodium, and like this
leaves the body chiefly through the kidneys. To a certain
extent, however, rubidium also is eliminated through the
intestinal tract.

1 Mendel and Thachek: American Journal of Physiology L904, XI
p 14.

2 Personal letter dated New Baven, Connectieut, July 123, 1905.

314 PHYSIOLOGY OF ALIMENTATION.

The question of the excretory function of the alimentary-
tract has also been studied by J. B. MacCallum.1 This ob-
server has confirmed the experiments of some of the older
students of oedema that sodium-chloride solutions of the
osmotic concentration of the blood, or somewhat higher, -
when injected into the circulation of rabbits, cause a greatly
increased secretion of fluid into the intestinal tract. The
amount of fluid eliminated in this way varies both with the
rate and the quantity of the salt solution that is injected.
In one experiment in which 500 c.c. of salt solution were
injected intravenously, 14.46 percent were eliminated through
the intestinal tract. In another experiment 9 percent of
the total quantity of fluid injected was eliminated in this
way, and in a third, 10.25 percent. When the kidneys are
removed the amount excreted through the intestine is some-
what higher — 16.6 percent in one experiment. The intes-
tinal tract behaves therefore not unlike the kidneys under
similar circumstances. We are well acquainted with the
effect of intravenous injections of salt solutions in increasing
the output of urine. The increased secretion from the intes-
tinal tract is therefore not unlike the polyuria brought
about by similar means.

Interestingly enough, the other salts which bring about
an increased secretion of urine also bring about in a similar
way an increased secretion from the intestine. Experiment
has shown that the diuretic salts and the saline cathartics
are the same. So far as the excretion of water from the body
is concerned, therefore, we may well look upon the intestinal
tract as supplementary to the kidneys.

MacCallum made no determinations of the relative amounts
of the various salts which are eliminated through the kidneys
and intestine. It is clear from Mendel's experiments, how-
ever, that these must differ with the different elements. The

1 MacCallum: University of California Publications, Physiology,
1904, 1, p. 125.

ALIMENT l/.T TRACT AS AN EXCRETORY SYSTEM. 315

former has, however, found in his own experiments and had
collected facts from the litera fcure which sh >w tha I lubstances
which are ordinarily believed to be excreted chiefly or ex-
clusively through the kidneys are eliminated also by the
intestine. Claude Bernard found as far back as L859 that
urea occurs in the saliva and the gastric juice, and tli.it in
nephritis and after removal of the kidneys this substance is
excreted to a large extent by the intestine. From this fact
Claude Bernard concludes that the intestine may supple-
ment the kidneys in eliminating the various constituents of
the urine. The presence of urea in the intestinal juice of
sheep has been demonstrated by Pregl, and MacCallum
found this substance normally present in the same secretion
of the rabbit.

Of great interest is the fact discovered by MacCallum that
in a certain form of experimental diabetes the sugar is elimi-
nated, not only by the kidneys but also through the intestinal
tract. As first shown by Bock and Hoffmann and con-
firmed by KtJLz's and my own experiments, the intravenous
injection of rabbits with a sodium chloride solution of a some-
what higher concentration than the sodium chloride in the
blood brings about a transient excretion of glucose in the
urine.1 The observations of MacCallum show that under
these conditions sugar is eliminated also by the stomach and
intestine and apparently in about the same concentration as
in the urine. The excretion of the carbohydrate through
the intestinal trad can he made more apparent by removing
the kidneys, but even when they are left intact, sugar is
nevertheless excreted to some extent through the alimentary
tract. How great a role this route of excretion plays in the
ordinary cases of human diabetes is an interesting question
which has not as yet been investigated.2

'Martin II. Fischer: University of California Publications, Physi-
ology, 1903, I . pp. 77 : x 1 1 < 1 s7; l'i i Bgj r's AjTchiv., 1904, CVJ . p. 80; ibid.,
1905, CI X, p. 1.

2 My analysis of the fircos in two cat of human diabetes failed

316 PHYSIOLOGY OF ALIMENTATION.

The above facts, to which many more could be added
from medical literature, begin to give us an experimental
foundation for the long-established empirical practice of
utilizing the intestinal tract as an organ of excretion in those
diseases in which the function of the kidneys is impaired.
Not only has it been shown that for many substances the in-
testinal tract is the chief excretory organ, but also that the
intestine behaves in many respects not unlike the kidneys.
The same salts which act as diuretics act as cathartics, and
sugar and urea, which by many have been looked upon as
substances excreted only by the kidneys, may be lost from
the body through the intestinal tract also.

The problems which suggest themselves in this domain of
the excretory function of the alimentary tract, so often touched
upon but so little studied, are many. In how far can we sub-
stitute the activity of the intestinal tract as an excretory
organ for that of the kidneys in ridding the organism of the
various substances found in the urine both in health and
disease? Each of the substances found in this excretion,
from the ordinary salts to the most complex organic poisons,
such as the toxins, will have to be investigated with this
problem in mind, and the results obtained may well be ex-

to show sugar in sufficient amounts to be recognized by ordinary
laboratory methods even when 600 to 700 grams of sugar were being
excreted in the urine. According to experiments carried on with
Gertrude Moore, practically no sugar escapes through the gastro-
intestinal tract in rabbits rendered diabetic through puncture of the
medulla. But this happens in such rabbits as soon as a sodium
chloride solution is injected intravenously. A sodium chloride solu-
tion too dilute to bring about a glycosuria by itself is able to do this.
The sodium chloride therefore renders the gastro-intestinal mucosa
permeable in one direction to a substance to which it was formerly
impermeable. An analysis of MacCallum's experiments shows that
he never injected sodium chloride in sufficient amounts to bring about
a glycosuria. He rendered his rabbits diabetic through the use of
morphin, and obtained sugar in the gastro-intestinal secretions through
subsequent intravenous injections of sodium chloride solutions.

ALIMENTARY TRACT AS AN EXCRETORY SYSTEM. 317

peeted to be of the utmost practical value in medicine. It
was shown above to how great an extent certain inorganic-
substances are eliminated by the alimentary tract. Flexner
has found that the toxin of the Shiga bacillus, no matter
how introduced into the body, is eliminated through the
intestinal tract, and in this elimination gives rise to the
ulcers found in the dysentery produced by this organism.
The recognition of the fact that morphin is secreted into
the stomach, even when subcutaneously introduced, has led
to the practice of gastric lavage for morphin poisoning; and the
knowledge that arsenic appears in the gastro-intestinal tract,
no matter how it is given, has led to scientific methods of
recognizing cases of poisoning by this element, not only for
diagnostic but also for medico-legal purposes.

2. The Character of the Alimentary Contents. The Faeces.
— The alimentary contents differ markedly in general appear-
ance and chemical composition in the various portions of the
alimentary tract. The reasons for this are readily ap-
parent. Not only does the food of different animals differ,
but it is not always the same in the same animal. In its
passage from the mouth to the anus it is acted upon by the
various portions of the canal through which it passes, and
changes are wrought in it of a mechanical and chemical char-
acter. Not only is its physical state of aggregation pro-
gressively altered in this way, but it has poured out upon it,
one after the other, a number of secretions, each of which, by
virtue of the substances contained in it; alters the chemical
composition of the alimentary contents. The metabolic
products excreted by the bacteria accomplish a similar end.
To the changes brought about in this way must be added
those induced through the absorption from the alimentary
contents of certain of the substances contained in them.
All these are together responsible for the progressive change
which the food suffers in its passage from the mouth to the
anus.

The food enters the mouth in a state of coarse division,

318 PHYSIOLOGY OF ALIMENTATION.

and through the action of the teeth is more finely divided.
With most individuals the food as it slips into the stomach
still contains large masses of undivided food, made up more
particularly of pieces of meat and smaller but still coarse
pieces of boiled potato, bread, etc. The mechanical action
of the stomach, together with the action of the large quanti-
ties of gastric juice poured out under physiological condi-
tions upon the food in this locality, serves to change even
the external appearance of the mixed food. Not only are
the larger pieces of starchy food broken into smaller ones
through the muscular contractions passing over the stomach,
but pieces of swallowed meat suffer similar changes in their
state of aggregation. The connective tissue found in them
is acted upon by the gastric juice and the cellular elements
in consequence are allowed to fall apart. Fatty tissues suffer
a similar change, and the fat contained within the cells
becomes free. If any fats have been consumed which at
ordinary temperatures are solid, but melt at body temper-
atures, these melt. The formation of peptones from the
protein of the meal imparts to the gastric contents a bitter
taste.

The acid, liquid, partially digested gastric contents pass
over in small amounts into the duodenum. Here they have
poured out upon them, as soon as they pass the pancreatic
duct, the bile and pancreatic juice. The color of the bile im-
parts itself to the alimentary contents, and the alkaline reac-
tion of the pancreatic juice reduces the acidity of the food as
it has escaped from the stomach. Throughout the small in-
testine the food exists only as a sticky, mucinous, brownish-
yellow mass which adheres more or less closely to the mucous
membrane of the alimentary tract. The viscosity of this
mass increases gradually from above downward, and no-
where throughout the small or large intestine do the alimen-
tary contents show to the naked eye any of the character-
istics of the food originally consumed by the individual.
These are quite effectually lost even in the stomach after

ALIMENTARY TRACT AS AN EXCRETORY SYSTEM. 319

digestion has gone on for two or three hours. The yellowish-
brown contents of the small intestine assume a somewhat
darker color when the ileocecal valve is passed, and from
here down to the anus the alimentary contents lose water,
and in consequence increase in consistency very rapidly.
Semisolid scybala begin to appear in the transverse and
descending portions of the large intestine, and in the lower-
most portions of the large bowel the faeces proper are formed.
Throughout the small intestine the alimentary contents have
no faecal odor under ordinary circumstances. This is de-
veloped after the ileoccccal valve is passed.

The question of the reaction of the gastro-intestinal contents
has within the last few years come up again for discussion.
In consequence of more careful analyses, made possible through
advances in our knowledge of indicators, some of our older
ideas regarding the reaction of the intestinal contents will
have to be set aside and newer ones adopted. The reaction
of the gastric contents after these have remained in the stomach
for some time is, under normal circumstances, acid, and this
fact has never been disputed since the middle of the last cen-
tury. Broadly speaking, the contents of the small intestine
have always been considered alkaline. Except for the first
few inches of duodenum in which the fresh acid gastric con-
tents may be found, the contents of the remaining portion of
the alimentary tract were considered alkaline in reaction,
because they had poured out upon them the "pronouncedly
alkaline" secretions of the pancreas, liver, and intestine
itself. Neglecting for the time being the reaction of these
juices, let us ask what means were employed to ascertain the
reaction of the gastro-intestinal contents? For the most
part only one indicator was used to determine their acidity
or alkalinity, litmus, and this in its poorest form, as litmus
paper. Litmus in any form, however, is an exceedingly
fallacious indicator, at times even useless, in solutions in
which carbonates are present, for litmus is not sufficiently
sensitive toward carlonates. For this reason litmus may

320 PHYSIOLOGY OF ALIMENTATION.

even show an alkaline reaction in solutions which are really
neutral or even acid.

A number of authors have in recent years employed in-
dicators other than litmus (such as lacmoid, phenolphthalein,
methyl orange, alkanna, rosolic acid, alizarin, curcuma and
trapsBolin) to ascertain the reaction of the intestinal con-
tents. Munk,1 who experimented in this way on dogs and
hogs fed on various diets after a period of fasting — diets
predominantly protein, or protein and fatty, or mixed in
character — comes to the following conclusions: The con-
tents of the duodenum, jejunum, or ileum, in carnivorous as
well as in omnivorous animals, no matter how fed, at no time
show an alkaline reaction, if only indicators sufficiently sensi-
tive to indicate the presence of carbonates and fatty acids be
employed. On a pure meat diet the duodenal and upper
jejunal contents are distinctly even though only faintly
acid. Beyond this point and to the ileocsecal valve the
intestinal contents are neither definitely acid nor alkaline,
and may, in consequence, be considered neutral. As soon as
fat is added to the diet, that is, protein and fat are fed to-
gether, the contents of the entire small intestine show an
acid reaction, attributable, no doubt, in the main to the
presence of free fatty acids formed through the action of
lipase upon the neutral fats. In fact, under no circum-
stances, even when large amounts of carbohydrates are given
together with protein, do the contents of the jejunum or ileum
ever show an alkaline reaction.

The experimental observations of Munk are corroborated by
clinical findings on human beings. Macfadyen, Nencki, and
Sieber,2 who observed two cases of fistula of the ileum just
above the ileocsecal valve, found that the contents of the
alimentary tract when they passed this point were always
acid in reaction when the patients were given a mixed diet.

1 Munk: Centralblatt fur Physiologie, 1902, XVI, p. 33.

2 Macfadyen, Nencki, and Sieber: Archiv fur experimentelle
Pathologie und Pharmakologie, 1891, XXVIII, p. 311.

ALIMENTARY TRACT AS AN EXCRETORY SYSTEM. 321

The acidity was due to organic acids. These acids no doubt
inhibit the development of those bacteria which are capable
of producing putrefaction of the protein substances present
in the small intestine. For this reason no protein putrefac-
tion occurs here under normal circumstances, or only rarely.

If what has been said above concerning the reaction of
the intestinal contents is true, then how are we to reconcile
it with the observations that have been made on various fer-
ments and their behavior toward acids and alkalies? Alkali-
proteinase, for example, is generally stated to act best in an
alkaline medium. In the body of various animals, including
man, this ferment must however work for the most part in
an acid, at the best in a neutral medium. Evidently, there-
fore, alkali-proteinase does not work under the most favorable
conditions, so far as reaction of surrounding medium is con-
cerned, in the body; or else the statements of the various
students of the effect of acids and alkalies on alkali-proteinase
must be revised. So far as the former of thtse possibilities is
concerned, we know that alkali-proteinase will act in neutral
or acid media, even very powerfully in neutral media. So far
as the latter possibility is concerned, it is entirely probable
that the use of indicators better adapted to the investigation
of the problem will show that the alkalinity in which al-
kali-proteinase acts best is lower than we formerly supposed,
and that some of the solutions in which alkali-proteinase is
known to act very well and which are ordinarily stated to
be alkaline are really neutral or even acid in reaction. Under
normal circumstances, therefore, alkali-proteinase may still
be considered as acting in the intestine under only slightly
unfavorable circumstances.

What has been said of alkali-proteinase holds also for the
other enzymes. Unquestionably the acid reaction of the
intestinal contents may be of service t'> certain of the fer-
ments, such, for example, as the acid-proteinase of the
stomach and duodenum. Finally, even if the acid reaction
of the contents of the small intestine reduces the activity

322 PHYSIOLOGY OF ALIMENTATION

of the digestive ferments found here, it reduces still more
markedly that of the ferments found in the bacteria, for the
growth of these is decidedly kept in check throughout this
hollow viscus, and their putrefactive action upon the food
(which, under pathological conditions, may become of a
serious character) prevented to a large extent.

The amount of faeces cast off by an animal is depend-
ent upon the amount and character of the food consumed.
Other things being equal, a large amount of food will yield a
greater amount of excremehtitious material than a smaller one.
The extent to which a food can be absorbed is however of
great importance. Fine white-flour breads are, for example,
absorbed more perfectly than rye or whole-wheat breads,
because they represent more nearly pure starch in a form that
can be acted upon by the digestive ferments. Mashed potatoes
yield less faecal matter than boiled potatoes, for in the former
the cellulose membranes surrounding the cells are more per-
fectly broken than in the latter, and the starch absorption is
in consequence more perfect. Because of the large amount
of cellulose they contain, the vegetable diets in general yield
a larger amount of faecal matter than meat diets. The faeces
do not, however, represent only remnants of food that can-
not be digested, but also a certain amount that can be, but,
for various reasons, has not been digested. In addition it
must not be forgotten that the secretions of the gastro-
intestinal tract itself and of the glands connected with it
contribute largely toward making up the body of the faeces.

The color of the faeces is variable. A meat diet yields
dark, one of bread, lighter faeces. The color is determined in
large part by the bile, being gray in its absence, yellowish or
yellowish brown in its presence. For the most part, it is not
the bile pigments themselves that give this color, but certain
of their derivatives formed after the bile has escaped into the
intestine.

INDEX OF AUTHORS.

Wherever subjects are presented at greater length it is indicated by bold-
faced type.

Abderhalden, on acid-proteinase, 121; on peptides-, 124; on
proteolysis, 126; on failure of tissues to digest themselves,
140; on protein synthesis, 141; on intestinal fermentation,
174; on duodenal juice, 245; on protein absorption, 305,
306, 307

Abelmann, on fat absorption, 297

Albertoni, on absorption of sugars, 285

Armstrong, on lactase, 157

Arrhenius, on electrolytic dissociation, 260

Bathazard, on movements of stomach, 7, 8

Bauer, on protein absorption, 299

Bayliss, on intestinal movements, 44; on secretin, 77, 212, 22S
229, 248 ; on secretin and biliary secretion, 238

Beaumont, 8; on the stomach, 188

Beciiamp, on maltase, 105

Beokek, on pancreatic secretion, 224

Beijerinck, on maltase, 105

Bence-Jones, 149

Bernard, Claude, on gastric juice, 67; on alkali-proteinase,
122; on intestinal tract, 136; on urea, 159; on saliva,
179; on paralytic salivary secretion, L82; on medulla and
salivary secretion, 184; on pancreatic fistula.', 215; on bile,
238; on urea in alimentary tract, 315

v. Berneck, on inorganic ferments, 94

Bernstein, on inhibition of pancreas, 222

323

324 INDEX OF AUTHORS.

Berreswil, on gastric juice, 67

Beyerinck, on lactase, 157

Bidder, on saliva, 64; on gastric secretion, 200, 204

Billitzer, on inorganic ferments, 94

Boas, on emptying of stomach, 16

Bock, on diabetes, 315

Bredig, on inorganic ferments, 94, 95

Brinck, on Micrococcus restituens, 307

Brotzu, on alimentary bacteria, 161

Brown, on maltase, 105

Brucke, on acid-pro teinase, 114; on swelling of fibrin, 118; on

protein absorption, 299
Bruno, 119; on bile, 237, 239
Brunton, on acid-proteinase, 115
Bucheler, 103, 106, 155
Buchner, on zymase, 81; on acid-proteinase, 119

Cannon, on deglutition, 4, 5, 6 ; on salivary digestion in stom-
ach, 15, 104; on pylorus, 16, 17, 20; on gastro-intestinal
movements, 7, 8, 12, 15, 22, 43, 44, 46

Chigin, on gastric fistulse, 189; on gastric secretion, 192, 193,
198, 205, 210; on adaptation of digestive glands, 234

Cohen, 79, 87, 89, 107

Cohnheim, on protease, 75, 146; on amylase, 99; on absorp-
tion, 279, 280

Colin, on saliva, 186

Connstein, on fat absorption, 289

Conradi, on curdling of milk, 112

Cremer, on glycogen, 103

Czerny, on protein absorption, 299 ; on removal of stomach, 302

Dakin, on arginase, 76, 158, 308

Dastre, on bile, 238, 239

Day, on salivary digestion in stomach, 15

Delezenne, on pancreatic proferments, 70; on enterokinase,

246; on pancreatic secretin, 248
Denathe, on sucrase, 154
Deucher, on protein absorption, 304
Dolinski, on pancreatic secretion, 224, 225

INDEX OF AUTHORS. 325

Dominici, on alimentary bacteria, 162

Duclai \, on sucrase, 154; on alimentary bacteria, 166

Edkins, on acid-proteinase, 109; on gastric secretion, 212
EPPRONT, 103, 106, 1")"); on sucrase, L56
ElJKMANN, on diffusion of colloids, L'SS

Ernst, on colloidal platinum, 96

Eschbrich, on alimentary bacteria, 161, 164; on B. lastis

aerogenes, 163
Esselmont, on intestinal movements, 46
Ewald, on emptying of stomach, 1G

Faber, on gastric elimination, 312

Fischer, Emil, on acid-proteinase, 121; on peptides, 124; on
protein synthesis, 140; on lactase, 157

Fischer, Martin H., 79, 87, 89, 107 ; on diabetes, 315

Flexner, on toxin excretion, 317

Fodera, on pancreatic fistula?, 216

Friedenthal, on acid-proteinase, 115; on absorption of col-
loids, 288

Friedlander, on absorption of acid-albumin, 299

Frouin, on pancreatic proferments, 70; on enterokinase, 246

Fubini, on intestinal movement, 46

C.erhardt, on aliment ary bacteria, 161
Gilbert, on alimentary bacteria, 162
Ginsberg, on carbohydrate absorption, 280
Glaessner, on pancreatic juice, 69; on human pancreatic secre-
tion, 226, 227, •_,.!,.>; on bile, 239
(Ii.iwsm, on salivary fistula?, 177
Gmelin, on gastric juice, 07
( iB \n \M. on colloid-, '_'.")!

Grutzner, on movements of intestine, 22; on estimation of
proteolysis, 130

Gl MILEWSKI, on saline cathartics, IS

IlxMi.i RQER, on human intestinal juice, 71. 75, 76, 77

Hammarsten, on bile, 72 ; on caseinase, 110; on casein, Hi; on
calcium and milk, 112; on acid-proteinase, 118

326 INDEX OF AUTHORS.

Hanford, on alimentary elimination, 312

Hanriot, on reversible action of lipase, 151, 153; on mechan-
ism of fat absorption, 289

Harley, on pancreas, 304

Hedon, on fat absorption, 297

Heidenhain, on gastric juice, 67; on gastric fistulse, 189, 215,
246; on gastric secretion, 210; on bile, 239; on absorption,
280

Hekma, on human intestinal juice, 74, 75, 76, 77

Heron, on maltase, 105

Herzog, on caseinase, 110; on protein synthesis, 143

Hewlett, on action of bile, 240

Hill, on reversible action of maltase, 106

Hirsch, 8; on the pylorus, 12, 16, 20

Hober, on molecular weight and osmotic pressure, 253; on
absorption of salts, 276

Hoffmann, on diabetes, 315

Hofmeister, 8; on catharsis, 50; on peptones, 146; on gela-
tine plates, 267; on assimilation of carbohydrates, 284

Hoppe-Seyler, on saliva, 62

Ikeda, on inorganic ferments, 94

Jones, on tubercle bacilli, 162
Jurgens, on gastric secretion, 200

Kanitz, on alkali-proteinase, 123

Kastle, on lipase, 75; on reversible action of lipase, 151; on

mechanism of fat absorption, 289
Ketscher, on gastric secretion, 202
Kjeldahl, on amylase, 103; on sucrase, 156
Kladnizki, on bile, 237
Klein, on alimentary bacteria, 162
Klemensiewicz, on gastric juice, 189
Kleyn, on alimentary bacteria, 162
Kohlbrtjgge, on alimentary bacteria, 161, 164
Konowaloff, on gastric juice, 66
Kossel, on arginase, 76, 158, 308
Kotljar, on appetite juice, 205

INDEX OF AUTHORS. 327

Kovesi, on absorption of salts, 276

Kroeber, on maltose, 100

Kronecker, on deglutition, !, 5, 0

KuDREWETZKY, oil nerve supply of pancreas, 223

Kuhne, on enzymes, SI ; on peptones, 121, 124, 148

Kulz, on diabetes, 315

Kunkel, on gastric elimination, 311

Kutscher, on protein absorption, 301

Kuwsciiinski, on pancreatic secretion, 225

Labord, on acid-proteinase, 119

Langley, on acid-proteinase, 119; on salivary secretion, 179,

180
Langstein, on acid-proteinase, 121
Latschenberger, on protein absorption, 299
Lawrow, on acid-proteinase, 121
Lepage, on nervous control of pancreas, 228
Lintner, on maltase, 106
Lintwarew, on closure of pylorus, 21
Lobassoff, on appetite juice, 205, 208; on oils, 211
Loeb, on muscle and nerves, 49
Loevenhart, on lipase, 75, 151; on curdling of milk, 112; on

mechanism of fat absorption, 2S9, 291
Ludwig, on salivary secretion, 181, 187; on pancreatic fistula?,

215; on protein absorption, 302

MacCallum, on saline cathartics, 46; on alimentary excretion,

314, 315, 316
Macfadyen, on alimentary contents, 320
Malfetti, on acid-proteinase, 121
Mall, on intestinal movement, 27, 43
Manning, on human intestinal juice, 74
Martin, on bile, 239
Mathews, on salivary secretion, 1S2
Mays, on preparation of alkali-proteinase, 122
McIntosh, on inorganic ferments, 94
Meltzer, on deglutition, 4, 5, 6
Mendel, on paralytic secretion of intestine, 244; on protein

absorption, 302; on alimentary excretion. :;i l, 312, 313

328 INDEX OF AUTHORS.

v. Mering, on carbohydrate absorption, 286

Mester, on intestinal fermentation, 165

Mett, on estimation of proteolysis, 130

Meyer, on lipoids, 267, 269

Miller, on alimentary bacteria, 163

Minkowski, on fat absorption, 297

Mitscherlich, on saliva, 62

Miyamota, on acid-proteinase, 115

Moore, on saliva, 63; on sulphocyanate, 65; on gastric juice*

67; on fatty acids, 241; on solubility of fatty acids, 291,

297
Moore, Gertrude, on alterable permeability of intestine, 280}

on alimentary excretion of sugar, 316
Moser, on deglutition, 4, 5, 6
MtJLLER, Friedrich, 262 ; on fat absorption, 295
Munk, on reaction of saliva, 64; on carbohydrate absorption,

286; on fat absorption, 291, 294, 295, 296, 297; on protein

absorption, 299, 302; on reaction of alimentary contents,

320
Musculus, on starch digestion, 102

Nagano, on human intestinal juice, 74, 76; on absorption of

sugars, 285
Nencki, on acid-proteinase, 115; on intestinal contents, 320
Neumeister, on peptones, 146; on protein absorption, 299
Nielson, on inorganic ferments, 94, 97
Nirenstein, 119
Nuttall, on intestinal flora, 174

Ogata, on protein absorption, 302

Ohl, on saliva, 62, 63

Okotjneff, on protein synthesis, 143

Oppler, on intestinal fermentation, 165

Osborne, 113

Ostwald, 79; viscosimeter, 131; on mechanical affinity, 250

O 'Sullivan, on catalysis, 155

Overton, on lipoids, 267, 269, 271, 272

Pauli, on colloids, 182

Pavy, on non-digestion of stomach, 136

INDEX OF AUTHORS. 329

Pawi.ow, on gastric juice, 66, 1 L9; on salivary fistula, 177; on
saliva, 184; on gastric fistulae, 189; on cesophagotomy, 191;
on gastric secretion, 192, L93, 194, L95, 199, 200, 202; on
appetite, 203, 207, 209; on pancreatic fistula, 215; on
pancreatic juice, 221, 222; on bitters, 231; on adaptation
of digestive glands, 234; on intestinal secretion, 243; on
enterokinasc, 246, 247

Pbkelhaking, on acid-proteinase, 115

Penzoldt, on emptying of stomach, 16, 17, 18, 19; on ali-
mentary elimination, 311

Pfaundler, on acid-proteinase, 121

Pfleiderer, on acids and acid-proteinase, 116

Pfluger, on intestinal movements, 43 ; on fatty acids, 241

Popielski, on pancreatic proferments, 70; on nervous control
of pancreas, 228; on nerve supply of pancreas, 223

Popoff, on alimentary bacteria, 161

Pregl, on urea, 315

Prout, on gastric juice, 67; on pancreatic juice, 68

Rachford, on bile, 239; on digestion of fat, 288, 290

Reid, on absorption, 280

Reinders, on inorganic ferments, 94

Riciiet, on gastric secretion, 200

Ringer, on antagonism between sodium and calcium, 48

Rockwood, on fatty acids, 241; on solubility of fatty acids,
291, 297

Rohmann, on saline cathartics, 48; on intestinal juice, 73; on
absorption of sugars, 285

Rona, on feeding of amino-acids, 307

Rosenfeld, on fat deposition, 294

Rosenstein, on carbohydrate absorption, 286; on fat absorp-
tion, 294, 295; on protein absorption, 302

ROSSBACH, 8

Roux, on movements of stomach, 7, 8

Salaskin, on acid-proteinase, 121
Salkowski, on alkali-proteinase, 122
S.\i.\ kh.1, mi peptones, l 16
Samuely, on protein absorption, 305, 306

330 INDEX OF AUTHORS.

Sandmeyer, on fat absorption, 298

Schepowalniko w, on fat digestion, 239 ; on enterokinase, 246

Schiff, 119

Schild, on alimentary bacteria, 161

Schmidt, on saliva, 64; on gastric juice, 67, 200, 204

Schmidt-Mulheim, on protein absorption, 302

Schonbein, on inorganic ferments, 94

Schottelius, on alimentary flora, 175

Schumow-Simanowski, on gastric juice, 66; on cesophagotomy,
191; on gastric secretion, 192; on nervous control of gas-
tric secretion, 200, 202

Schtjtz, 8; on ferments, 131

Seemann, on protein absorption, 301

Seifert, on intestinal fermentation, 165

Serdjukow, on pylorus, 16, 20

Shiga, bacillus of, 317

Sieber, on acid-proteinase, 115; on intestinal contents, 320

Spiess, on salivary secretion, 181

Spiro, on colloids, 269

Spriggs, on estimation of proteolysis, 131, 144

Ssanozki, on gastric secretion, 200, 205

Starling, on movements of intestine, 22 ; on nervous control of
alimentary tract, 41 ; on pancreatic secretin, 77, 248 ; on
secretin, 212, 228, 229; on secretin and biliary secretion,
238; on absorption, 276

St. Martin, Alexis, 188

Sucksdorff, on alimentary bacteria, 161, 162

Talma, on antiseptic action of bile, 166

Tammann, 88

Taylor, on lipase, 151, 153

Thacher, on alimentary elimination, 311, 312, 313

Thierfelder, on intestinal flora, 174

Thiry, on intestinal juice, 73 ; on intestinal fistulse, 243

Thompson, 119, 189, 200, 209, 215, 217, 221, 224, 225, 231, 237

Tiedemann, on gastric juice, 67

Tompson, on catalysis, 155

Tubby, on human intestinal juice, 74

Uschakoff, on gastric secretion, 203

INDEX OF AUTHORS. 331

van't Hoff, laws of, 259, 260

Vella, on intestinal juice, 73; on intestinal fistula, 243

Vernon, on protease, 149; on lactase, 236

Ville, on fat absorption, 297

Voit, on protein absorption, 299

von Bekneck, on inorganic ferments, 94

von Merino, on carbohydrate absorption, 286

Walther, on pancreatic secretion, 217, 225; on pancreatic
juice, 220; on adaptation of digestive glands, 234

Weinland, on pancreatic amylase, 91; on antiproteinase, 65,
133, 144; on failure of autodigestion of alimentary tract,
135; on intestinal ulcers, 139; on lactase, 157; on adapta-
tion of glands to food, 234, 236

Wertheimer, on nervous control of pancreas, 22S

\\ kstphalen, on bile, 71

Wherry, on cholera, 167

Williams, on bile, 239

Wroblewski, on acid-proteinase, 119

Zunz, on acid-proteinase, 121

INDEX OF SUBJECTS.

Wherever subjects are presented at greater length it is indicated by bold-
faced type.

Absorption, 249; problem of, 249; nature of substances con-
cerned in, 250; forces active in, 250, 2.">7; role of osmotic
pressure in, 262, 263, 264, 265; role of colloids in, 267; of
salts, 274 (see also Salts); of water, 2(52 269; of carbo-
hydrates, 2S2 (see also Carbohydrates); of fats, 287 (see
also Fats); of proteins, 299 (see also Proteins); of lipoid-
soluble substances, 268, 278, 279; effect of chemicals on,
280

Absorptive system, alimentary tract as, 249

Acetic acid, 106

Acid-proteinase, 114; distribution of, 114; in stomach, 67, 114;
preparation of, 114; chemical character of, 115; effect of
acids on, 116; effect of chemical substances on, 118; effect
of temperature on, 120; action of, on fibrin, 120; products
of digestion by, 121 ; compared with alkali-proteinase, 122;
role of, in protein absorption, 300, 301

Acids, as electrolytes, 260; organic, of alimentary contents, 321

Adaptation of digestive glands to food, 234; mechanism of, 236

Affinity, mechanical, 250

Alcohol, ethj I. L06

Alcohols, diffusion of, into protoplasm, 271 ; absorption of, by
alimentary tract , 27S, L'79

ALDEHYDES, diffusion of, int.. protoplasm, 271

Alc-e, behavior of, in various solutions, 270, 271

333

334 INDEX OF SUBJECTS.

Alimentary contents, character of, 317; progressive changes
in, 317; reaction of, 319, 320; effect of, on alimentary fer-
ments, 321, 322

Alimentary tract, general functions of, 1 ; movements of food
through, 36; nervous control of, 41; effect of emotion on
movements of, 44, 45, 46; failure to digest itself, 135, 140;
bacteria of (see Bacteria) ; physiological connection between
different portions of, 248; as absorptive system, 249; as
excretory system, 311; predominant permeability of, in
one direction, 279, 280

Alkali-proteinase, of pancreas, 69; preparation of, 122;
effect of medium on, 123; effect of temperature on, 123;
effect of concentration of ferment on, 124 ; cleavage of pro-
teins by, 124; end products of digestion by, 125; and bile,
241 ; role of, in protein absorption, 300, 301

Alkalies and gastric secretion, 232

Amino-acids, 121, 124, 126; in intestinal contents, 301

Amphoproteinase, 129

Amylase, 99; of saliva, 62, 65; of pancreas, 69; of intestine,
75 ; sources of, 99 ; salivary and pancreatic compared, 100 ;
effect of external conditions on, 100; action of, on starch,
101; effect of temperature on, 103; possible reversible
action of, 103; and glycogen. 103; separation from mal-
tase, 105 ; and bile, 241

Amylopsin (see Amylase)

Anacidity, consequences of, in stomach, 165 -^,,

Animal membranes (see Membranes)

Antiferment, 80, 133 (see also Antiproteinase)

Antipepsin (see Antiproteinase)

Antiproteinase, of stomach, 68; of intestine, 96, 133; prep-
aration of, 133; action of, 134; effect of heat on, 134;
general distribution of, 137 ; consequences of lack of, 137 i

Antitoxins, 139

Antitrypsin (see Antiproteinase)

Appetite, 203; as gastric excitant, 203; physiological impor-
tance of, 230

Appetite juice, 204, 205; physiological importance of, 205

Arginase, of intestine, 76; and arginin, 158, 308

Arginin, digestion of, 76; and arginase, 158

i\i>i:x OP subjects. 335

Absbnic, elimination of, through s\ ach, 311

Asi'vms, 133 (see also A.ntipmh inase)
Ask, in naming ferments, 82

Assimii. \ riox limits of carbohydrates, I'M, l_',S.~>

Bacillus, coli communis, 164; putrificus, 164; subtilis, 164;
acidophilus, 164

Bactkkia of VLIMENTARY TRACT, 160; existence of, 161 j num-
ber of, Kii ; weight of, 162; kinds of , 162; distribution of,
165; destruction of, in stomach, 165; destruction of, in
intestine, 166; products of, 168

Bacterium, lactis aerogenes, 163

BARIUM, alimentary excretion of, 313

Bases, as electrolytes, 260

Bence-Jones PROTEIN, 1 111

Bile, 70; amount of, 71; physical character oF, 71; chemical
composition of, 72; secretion of (see Biliary secretion);
functions and physiological importance of, 237, 23S; and
digestion of fats, 238, 239, 240, 241 ; as adjuvant to pan-
creatic ferments, 241; as solvent for fatty acids, 241; as
inhibitor of gastric digestion, 242; antiseptic action of, 242;
as aid to peristalsis, 242; as activator of proferments, 242;
role of, in fat absorption, 296, 297, 298

Bile acids. 72

Bile pigments, 72

BlLIARY secretion, 237; into intestine, 237; in relation to
feeding, 237; effect of foods on, 238; mechanism of, 238;
and pancreatic secretin, 238

Bismuth subnitrate, and study of gastro-intestinal move-
ments, 7

Bitters, 231

Br ret test, and peptides, 128, 1 12

Blood, pressure of, and salivary secretion, 187; red corpuscles
of, 256; constancy of protein composition of, 305, 306

Bread, and gastric secretion, 198; and pancreatic secretion, 220

Bin wkk's islands, secretion of, 245

Calch m, antagonistic action of, toward sodium, is
CalCI i.i, salivary, 65

336 INDEX OF SUBJECTS.

Cane-sugar (see Sucrose)

Capillary forces, 250

Carbohydrates, rate of leaving stomach, 17; absorption of,
282, 286 (see also Absorption); found in the food, 282;
form of absorption of, 283 ; action of enzymes on, 283, 284 ;
assimilation limits of, 284, 285

Casein, 111

Caseinase, of stomach, 67; of pancreas, 69; properties of, 110;
coexistence with proteolytic ferments, 110; preparation of,
110; effect of external conditions on, 111; and antipro-
teinase, 145

Catalysis, 79; rate of, 85; effect of external conditions on, 85;
effect of temperature on, 87; effect of products on, 89 (see
also Catalyzers)

Catalytic agents (see Catalyzers)

Catalyzers, 79; positive, 79; negative, 79; inorganic, 79;
organic, 80

Cathartics, action of saline, 46; increased peristalsis through,
47; increased secretion produced by, 48; antagonistic ac-
tion of calcium on, 48 ; and secretion of water, 267

Cell-wall, morphological, 257

Centre, for oesophageal movements, 42 ; for gastric movements,
43

Cerebrin as a lipoid, 274

Chemical equilibrium, 106

Cholesterin as a lipoid, 274

Chorda tympani, and salivary glands, 178

Chyle, 294

Cocoa butter, deposition of, after feeding, 294

Coefficient of distribution, 272

Colloidal solutions of noble metals, 94; methods of pre-
paring, 94; effect of temperature on, 95 ; incompleteness of
reactions catalyzed by, 97; reversibility of action of, 97
(see also Colloids)

Colloids, 251; affinity of, for water, 250, 251; amorphous
character of, 251; solutions of, 252; osmotic pressure of,
252 ; typical, 252 ; molecular weight of, 252, 253 ; diffusion
of, 253; and absorption, 254; examples of, 254; absorption
of, 288; diffusion of colloids into, 288, 289

INDEX OF SUBJECTS. 387

Condiments, 231

Crystalloids, 251; crystalline character of, 251; solutions of,
'_'.">_'; osmotic pressure of, 252; molecular weight of, 252,
253; diffusion of, 253; and absorption, 254; examples of,
25 I

Cul-de-sac, gastric, 189

I Systicerci, l ■">•")

Cytasi:, 170; ami cell nlose, 284

Dead matter, L35, 136

Defecation, acl of, 35; lime of, 40

Deglutition, voluntary control of, 4; involuntary character of,
4; experimental observations on, 4; muscles concerned in,
4; of liquids, 5, 6; of solids, 5,6; in cats, 5; in fowls, 5;
in dogs, 6; in man, 6; time required for, 6; nervous con-
trol of, 41; cent re for, 41

Dextrin, 99, 102; and maltose, 104

Dextrose, and maltase, 104; as chief sugar of the body, 282,
283

Diabetes, starvation, 2S4, 285; from sodium chloride injec-
tions, 315

Diastase (see Anu/lnsr)

Diet and gastric secretion, 1!»2; and pancreatic secretion, 216

Diffusion, 250, 257, 25S; of colloids and crystalloids, 252, 253,
254, 2."i7, 258; of gases, 257; of chemicals into protoplasm,
271, 272

Diffusion velocity, of salts, 276, 277

Digestive glands, adaptation of, to food, 234

Dissociation, electrolytic, 260

Distribution coefficient, 272

Duodeni m. passage of t 1 into, 14; effect of acid in, 20;

secretion of, 245; ferments found in, 245

1 >i 9ENTER1 , Shig \ bacillus of, 317

Electrolyte, 260

Electrolytic dissociation, 260

Emotion, effect of, on alimentary movements, 44

Emi lsifk \ 1 1"\ of fats, 240

Emulsin, 88

338 INDEX OF SUBJECTS.

Enemas, fate of nutrient, 52

Enteric juice (see Intestinal juice)

Enterokinase, 70, 76, 92, 244, 246; as activator of ferments,

246 ; nature of, 247 ; secretion of, 247
Enzymes, 81 (see also Ferments and Catalyzers)
Epithelium of intestine, selective permeability of, 256
Equilibrium, chemical, 106
Erepsin (see Protease)

Erythrite, diffusion of, into protoplasm, 271
Esters, diffusion of, into protoplasm, 271
Ethyl acetate, 106
Ethyl alcohol, 106
Ethyl butyrate, analysis and synthesis of, by platinum, 97;

analysis and synthesis of, by lipase, 151
Excretion, as function of alimentary tract, 311; urinary and

alimentary, compared, 312, 314

Faeces, 317; amount of, 322; effect of food on, 322; color of,
322

Fat, rate of leaving the stomach, 17, 21 ; digestion of, 75 ; and
lipase, 149, 287; and gastric secretion, 239; emulsification
of, 240, 287, 288 ; chemical changes in, after ingestion, 287,
291; analysis of, in intestine, 291, 292; synthesis of, in
intestine, 293; absorption of (see Fat absorption)

Fat absorption, 287; amount of, 287; form in which it occurs*
and solubility of absorption products, 288 ; theories of, 289,
290, 291, 292, 293, 294; paths of, 294, 295; after occlusion
of thoracic duct, 295; velocity of, 295; amount of, 295;
role of bile in, 296, 297, 298; role of pancreas in, 296, 297,
298 (see also Fat digestion)

Fat digestion, as influenced by bile, 238, 239; as influenced by
intestinal and pancreatic juices, 239

Fatty acids, solubility of, 241, 242

Fermentation, 79; theories of, 83; velocity of, 85; effect of
hydrocyanic acid and hydrogen sulphide on, 98 ; in gastro-
intestinal tract, 165

Ferments, inorganic, 79; organic, 80; organized, 81; un-
organized, 81 ; nomenclature of, 81 ; general properties of,
83, 84; effect of temperature on, 86; decomposition of, 86;

TXDEX OF SUBJECTS. 339

reversibility of action of, 90; synthetic action of, 90; ana-
lytic action of , !)<); extraction of, 91 ; relation of, to pro-
ferments, 93; analogy between organic and inorganic, 97;

effect of poisons on, 97; action of human, 99

Ferment units, 220

Fistulas, gastric, 188; pancreatic, 215; biliary, 237; intestinal,
243; lymphatic, 286, 294, :;(>■-•

Food, and gastric secretion, 192; and pancreatic secretion, 216;
adaptation of digestive glands to, 234; physico-chemical
classification of, 250 ; chemical classification of, 250 ; phys-
ical character of, 251

Gall-bladder, fistula? of, 237

Gall-duct, fistula of, 237

Gas, diffusion of, 257, 258 ; pressure, 258

Gastric contents, 318

Gastric fistul.e, 188

Gastric juice, 60, 188; amount of, in twenty-four hours, 66;
acidity of, 66; ferments of, 67; hydrochloric acid of, 67;
quantitative variations in, 192; qualitative variations in,
193; acid of, 195 (see also Gastric secretion)

Gastric secretin, 211 (see also Secretin and Pancreatic se-
cretin)

Gastric secretion, regulation of, 188; effect of diet on, 192,
195; quantitative variations in, 192; qualitative variation
in, 193; effect of different foods on, 195; and meat, 198-
and bread, 198; and milk, 198; relation of nervous system
to, 200; excited by appetite, 203; chemical excitation of,
208; psychic excitation of, 203; and mechanical stimula-
tion, 209, 232; inhibition of, by sodium carbonate, 210;
inhibition of, by oils, 211; significance of physiology of,
230; effect of, on pancreas, 232; relation of, to other
organs, 233 (see also Gastric juice)

Giant molecule of caseinasc and proteinase, 110

Glands of Brunner, secretion of, 245

Glucase (sec Maltase)

Glycogen, 91 ; effect of amylase on, 103

Gram-molecule, definition of, 47

Hexone bases. 126

340 INDEX OF SUBJECTS.

Holothuria tubulosa, absorption in, 280
Hydrocarbons, diffusion of, into protoplasm, 271
Hydrocharis, plasmolysis of, 271
Hydrochloric acid, 195, 199
Hydrocyanic acid and fermentation, 98
Hydrogen peroxide, decomposition of, 94
Hydrogen sulphide and fermentation, 98

Icterus, 242

Ileocecal valve, 29

Immunity, 140; of tissues to ferments, 135

Indicators, 320

Indigo enzyme, 88

Intestinal contents, character of, 317

Intestinal fistula, 243

Intestinal juice, 73; physical character of, 73, 244; human,
74 ; ferments of, 75 ; antiproteinase of, 76 ; enterokinase of,
76; pancreatic secretin of, 79

Intestinal secretion, 237; regulation of, 243 (see also Intes-
tine)

Intestine, ulcers of, 139; contents of large and small, com-
pared, 318, 319; importance of, in protein digestion, 302;
and synthesis of protein, 306 ; permeability of epithelium of,
256, 267

Intestine, large, movements of, 29; antiperistalsis in, 29;
tonic constrictions in, 30 ; peristaltic waves in, 36 ; passage
of food into, 40; time food spends in, 40; effect of emo-
tional states on movements of, 45; absorption in, 30, 77;
secretion of, 77 ; enzymes in, 77 ; putrefaction in, 78

Intestine, small, movements of, 22; segmenting movements
in, 25, 26, 27; peristaltic movements in, 28; passage of
food into, 39; nervous supply of, 43, 44; effect of emo-
tional states on movements of , 45 ; secretion from, 243, 244 ;
relation of nervous system to secretion from, 244, 245;
paralytic secretion of, 244 ; secretion into isolated loops of,
244; absorption of peptones from, 309, 310

Invertase (see Sucrase)

Invertin (see Sucrase)

INVERT-SUGAR, 153

INDEX OF SUBJECTS. 341

Iodides, elimination of, 311

Ionization, 260

Ions, 260

isosmotic solutions, 268

Isotonic solutions, 268

Ketones, diffusion of, into protoplasm, 271
Kidneys and alimentary tract in excretion, 312
Kinase, 248

Lactase, of pancreas, 69; of intestine, 76, 157; "reversible ac-
tion of, 157; appearance of, in pancreas, 235; appearance
of, in small intestine, 235

Lactose, digestion of, 76; and lactase, 157; adaptation of
pancreas to, 234, 235

Lanolin, failure of absorption of, 289

Large intestine (see Intestine, large)

Lecithin, in digestion of triacetin, 241 ; as a lipoid, 274

Lipase, 149; of stomach, 67, 291 ; of pancreas, 69; of intestine,
75; distribution of, 150, 291 ; preparation of , 150 ; effect of
external conditions on, 150; reversible action of, 151; and
bile, 238, 239, 240, 241 ; destruction of, in stomach, 298

Lipoidal absorption, 268; development of conception of, 268,
269, 270

Lipoids, 274; role of, in absorption, 279

Living matter, 135, 136

Lymphatic fistula, Munk and Rosenstein's case of, 286, 294,
302

Maltase, 104; of saliva, 62, 65; of intestine, 76; separation

from amylase, 105; sources of, 105
Maltose, 99; digestion of, 76; and maltase 104; analysis of,

105; synthesis of, 108
Malt-sugar (see Maltose)

Mammals, appearance of lactase in, 234, 235, 236
M \\<;anese dioxide, 79
Mass-action, law of, 84
Mastication, 2; muscles concerned in, 3; nerves concerned in,

3; results of incomplete, 14

342 INDEX OF SUBJECTS.

Maxilla, movements of lower, 3

Meat, and gastric secretion, 198, 211; and pancreatic secretion,
220

Meat broth and gastric secretion, 211

Meat extract and gastric secretion, 211, 231

Meat juice, 231 ; and gastric secretion, 211

Mechanical affinity, 250; of colloids, 250

Mechanical stimulation and gastric secretion, 232

Membranes, 254; permeability of, 251; classification of, 254;
semipermeable, 255; permeable, 255; precipitation, 255;
of copper ferrocyanide, 255; of zinc ferrocyanide, 255;
animal, 255; behavior of crystalloids and colloids toward,
256; existence of, in organism, 256, 266; physiological, 257;
cells and tissues as, 257

Micrococcus restituens, 307

Milk, curdling of, 67, 111; mechanism of coagulation of, 111;
souring of, 111; effect of acids on, 111; and caseinase, 111;
theories of coagulation of, 112 ; relation of metals to curdling
of, 113; and gastric secretion, 198; and pancreatic secre-
tion, 217; as a food, 232

Milk-curdling ferment (see Caseinase)

Milk-sugar (see Lactose)

Mind, effect of, on organs, 184

Miniature stomach, 189

Molecular solutions, 47 (see also Solutions)

Monobutyrin, analysis and synthesis of, by lipase, 153

Morphin, elimination of, through stomach,, 311

Mouth, mucous glands of, 185

Movements, of mastication, 2 ; of deglutition, 3 ; of oesophagus,
5 ; of stomach, 6 ; of small intestine, 22 ;' of large intestine,
29; of food through alimentary tract, 36

Mucous glands, of mouth, 64 ; of oesophagus, 65

Mutton tallow, deposition of, after feeding, 294

Nervous control of alimentary tract, 41
Nitrogen tetroxide, 79
Non-electrolytEj 260

CEdema, theory of, 268

INDEX OF SUBJECTS. 343

(EsOPIIAGOTOMV, I'M

(Esophagi's, mucous glands of, 65

Olive-oil, digestion of, 239

Optimum temperature, 88

Ornithin, from arginin, 158

( )smoTIC cell, 202

Osmotic pressure, 258; of non-electrolytes, 259; of electrolytes

260; and semipermeable membranes, 259; laws of, 259, 200;

and migration of water, 204; behavior of cells toward

changes in, 205, 206
Oxidases, 82

Pancreas, amjdase of, 91; regulation of secretion of, 215-
fistuke of, 215, 210; normal excitants of, 224; adaptation
of food to, 234; role of, in fat absorption, 290, 297, 298 ;
importance of, in protein absorption, 302, 303, 304; re-
moval of, 303

Pancreatic duct, occlusion of, 303

Pancreatic juice, 08 ; physical properties of, 09 ; ferments of,
69; human, 69, 70; adaptation of, to food, 234 (see also
Pancreas and Pancreatic secretion)

Pancreatic secretin, 227

Pancreatic secretion, effect of diet on, 210; quantitative
variations in, 217; qualitative variations in, 217; and milk,
217; and bread, 220; and meat, 220; effect of vagus on,
222; effect of sympathetic on, 223; inhibition of, 222; psy-
chic excitation of, 225; normal excitants of, 224; effects of
acids on, 224; effects of salts on, 225; effect of fat on, 225;
effect of water on, 220; significance of physiology of, 230

Paralytic secretion, of saliva, 182; of small intestine, 244

Parotid gland, 170, 177; amount of secretion from, 179

Pepsin (see Acid-proteinasc)

Peptides, 124; synthesis of, 141; chemical reactions of, 142;
digestion of, by pancreatic juice, 142

Peptones, 124;, analysis of, 128, 147; and intestinal mucosa,
147; and gastric secretion, 211; effect of, on blood pres-
sure, 304

Permeability of gastro-intestinal tract in one direction, 279,
280

344 INDEX OF SUBJECTS.

Permeable membranes (see Membranes)

Plasmolysis, 269

Plastein, 143

Platinum, colloidal, 95

Polariscope, 108

Polypeptides, 125

Polyuria, 314

Precipitation membranes (see Membranes)

Proferments, 92; of alkali-proteinase, 92; of caseinase, 93;
of lipase, 93; of acid-proteinase, 93

Protagon, as a lipoid, 274

Protease, in intestinal juice, 75, 146; isolation of, 147; diges-
tion products of, 148; and alkali-proteinase, 148; and
casein, 148 ; substances attacked by, 148 ; effect of medium
on, 149 ; and proteolysis, 301 ; physiological importance of,
308, 309, 310

Protein digestion (see Proteolysis)

Proteinases, 75 (see also Acid-, Alkali-, and Ampho-proteinase) ;
recognition of, 129; quantitative estimation of, 129; rever-
sible action of, 140, 307, 308

Proteins, rate of leaving stomach, 17; digestion of, 75, 300,
301; synthesis of, 141, 146; absorption of, 299, 300; chan-
nels of absorption of, 302 ; role of stomach in absorption of,
302, 303, 304; role of pancreas in absorption of, 302, 303,
304; role of intestine in absorption of, 303; fate of after
digestion, 304, 305 ; synthesis of, in intestinal wall, 306, 307

Proteolysis, products of, 121, 125; mechanism of, 124; dia-
gram of, 127; cleavage theory of, 128

Proteolytic ferments (see Proteinases)

Proteoses, 124

Pseudo-solutions (see Colloids and Colloidal solutions)

Psychic secretion, 61; of gastric juice, 203; of pancreatic
juice, 225

Ptyalin (see Amylase)

Putrefaction of alimentary contents, 242

Pylorus, behavior of, during digestion, 12 ; opening and closing
of, 12, 14, 16; rhythmic opening of, 230

Radiographs, 7

INDEX OF SUBJECTS. 345

Reaction, reversible, 107; stationary, 107
Reaction velocity, effect of temperature on, 87

RECTAIi FEEMNG, 52

Rennet (see Caseinase)
Rennin (see Caseinase)
Reversible reaction, 107
Reversion, 106
Rubidium, excretion of, 313

Saccharomyces, 157
Saline cathartics (see Cathartics)

Saliva, 62, 176; submaxillary, 63; sublingual, 63; mixed, 64;
reaction of, 64 ; inorganic constituents of, 65 ; organic con-
stituents of, 65; ferments of, 65; chemical composition of,
179; secretion of, 176, 182; changes in, with different foods,
183 ; reflex secretion of, 185 (see also Salivary glands and
Salivary secretion)
Salivary calculi, 65
Salivary digestion, in stomach, 15
Salivary fistul/E, temporary, 176; permanent, 177
Salivary glands, 62 ; parotid, 62 ; exothermic reactions in, 182 ;

psychology of, 184; elimination of iodides through, 311
Salivary secretion, regulation of, 176, 177; relation of nerves
to, 178; accessory phenomena of, 180, 181 ; pressure changes
during, 181; reflex, 182, 185; and mechanical stimulation,
183; effect of alkaloids on, 181; effect of water on, 183;
effect of sand on, 183; effect of chemicals on, 1S3; effect
of foods on, 183; and blood pressure, 187
Salts, as electrolytes, 260; absorption of, 274, 275, 276, 277,
278, 279, 2S0, 281 ; behavior of red blood-corpuscles toward,
256; alimentary excretion of, 312, 313
Sea-sickness, 185
Secretin, pancreatic, 77, 227, 228; gastric, 211; as excitant of

biliary secretion, 238
Secretion, of bile (see Biliary secretion); of intestine (see In-
testinal secretion); pancreatic (see Pancreatic secretion)]
salivary (see Salivary secretion)
Segmentation, movements of, in intestine, 25, 26, 27 (see also
Intestine)

346 INDEX OF SUBJECTS.

Semipermeable membranes, 255 (see also Membranes)

Sham feeding, 66, 191

Sleep, effect of, on gastro-intestinal movements, 46

Small intestine (see Intestine, small)

Soaps, solubility of, 242

Sodium bicarbonate, and gastric secretion, 210

Sodium excretion, 313; urinary and alimentary, 314

Sodium silicate, absorption of, from intestinal tract, 256; ab-
sorption of colloidal, 288, 289

Sol, 95

Solutions, molecular, 47; equimolecular, 47; isotonic, 268;
isosmotic, 268 ; colloidal or pseudo (see Colloids and Col-
loidal solutions); crystalloidal, 251, 252, 253, 254

Soup, 231

Splanchnic nerve, effect of, on gastric movements, 42

Spleen, function of, during digestion, 247

Spores, 86

Starch, digestion of, 76 ; fermentation of, 99 ; effect of amylase
on, 101; effect of maltase on, 104; absorption of, 285, 286

Starvation diabetes, 284, 285

Stationary reaction, 107

Steapsin (see Lipase)

Stomach, movements of, 6; changes in shape of, during diges-
tion, 8, 9; antrum of, 8; pylorus of, 8; preantral part of, 8
muscle layers of, 9; as a reservoir, 12; emptying of, 12
time food spends in, 13, 17; movements of food within, 14
salivary digestion in, 15; passage of food out of, 16, 17
effect of vagus nerve on movements of, 42; effect of sym-
pathetic nerve on movements of, 42 ; effect of Auerbach
and Meissner's plexus on movements of, 43; effect of emo-
tional states on movements of, 45; post-mortem diges-
tion of, 136; why not self -digested, 137; ulcers of, 138;
bactericidal action of, 163; anacidity of, 165; bacterial
fermentation in, 165; importance of, in protein absorption
302, 303; removal of, 302; as excretory organ, 311; char-
acter of contents of, 318; fistulae of, 188; miniature, 189

Strontium, alimentary excretion of, 312

Sublingual gland, 176, 177

Submaxillary gland, 176, 177; amount of secretion from, 179

INDEX OF SUBJECTS. 347

SuCCUS ENTERICUS (sec Intestinal juice ;nul Intestinal Secretion)

Sucklings, lactase in, 235

Sucrase, of intestine, 70, L53; distribution of, 154; isolation

of, 154; effecl of external conditions on, 155
Sucrose, digestion of, 76, 153; inversion of, by sucrase, 155;

inversion of, by acids, 155;
Sugars, absorption of, 2S5; excretion of, into intestine, 315, 31G
Sulphocyanate, of saliva, 63
Sulphuric acid, manufacture of, 79, 83
Swallowing (see Deglutition)
Sympathetic nerve, effect of, in gastric movements, 42; effect

of, on pancreas, 223; and salivary secretion, 178
Synaptase, velocity of decomposition of, 88

Tartar, 65

Toxins, 139

Triacetin, pancreatic digestion of, 240, 241

Trifacial nerve, and salivary glands, 178

Triolein, analysis and synthesis of, 153

Trypsin (see Alkali-proteinase)

Typical colloids, 252 (see also Colloids)

Ulcers of alimentary tract, 138

Units, ferment, 220

Urea, from arginin, 158; in alimentary secretions, 315

Vagotomy, 201

Vagus, effect of, on gastric movements, 42; effect of, on intes-
tinal movements, 43; and gastric secretion, 222; and
pancreatic secretion, 222

VlSCOSIMETER, 131

Viscosity, determination of, 131; of proteins, 131, 144
Vital properties, SI

Water, with meals, 104; as excitant of gastric secretion, 226,
232; as excitant of pancreatic secretion, 22(1; absorption of,
262, 269 ; absorption of, by colloids, 250; osmotic absorption
of, 264 (see also Ahsur/ilion)

348 INDEX OF SUBJECTS.

Whey, 112

Worms, why intestinal, are not digested, 135

X-ray in study of intestinal movements, 7

Zymogens, 92, 93

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Van Deventer's Physical Chemistry for Beginners. (Boltwood.) i2mo, i 50

* Walke's Lectures on Explosives 8vo, 4 00

Ware's Beet-sugar Manufacture and Refining Small 8vo, cloth, 4 00

Washington's Manual of the Chemical Analysis of Rocks 8vo, 2 00

Weaver's Military Explosives 8vo, 3 00

Wehrenfennig's Analysis and Softening of Boiler Feed- Water 8vo, a 00

Wells's Laboratory Guide in Qualitative Chemical Analysis 8vo, 1 50

Short Course in Inorganic Qualitative Chemical Analysis for Engineering

Students i2mo, 1 50

Text-book of Chemical Arithmetic nmo, 1 25

Whipple's Microscopy of Drinking-water 8vo, 3 50

Wilson's Cyanide Processes nmo, 1 50

Chlorination Process iamo, 1 50

Winton's Microscopy of Vegetable Foods 8vo, 7 50

Wulling's Elementary Course in Inor^auic, Pharmaceutical, and Medical

Chemistry i2mo, 2 00

CIVIL ENGINEERING.

BRIDGES AND ROOFS. HYDRAULICS. MATERIALS OF ENGINEERING.
RAILWAY ENGINEERING.

Baker's Engineers' Surveying Instruments i2mo, 3 00

Bixby's Graphical Computing Table Paper 19^X24^ inches. 25

Breed and Hosmer's Principles and Practice of Surveying 8vo, 3 00

* Burr's Ancient and Modern Engineering and the Isthmian Canal . 8vo, 3 50

Comstock's Field Astronomy for Engineers 8vo, 2 50

Crandall's Text-book on Geodesy and Least Squares 8vo, 3 00

Davis's Elevation and Stadia Tables 8vo, 1 00

Elliott's Engineering for Land Drainage nmo, 1 50

Practical Farm Drainage i2mo, 1 00

*Fiebeger's Treatise on Civil Engineering 8vo, 5 00

Flemer's Phototopographic Methods and Instruments • 8vo, 5 00

Folwell's Sewerage. (Designing and Maintenance.) 8vo, 3 00

Freitag's Architectural Engineering. 2d Edition, Rewritten 8vo, 3 50

French and Ives's Stereotomy 8vo, 2 50

Goodhue's Municipal Improvements i2mo, 1 75

Gore's Elements of Geodesy 8vo, 2 50

Hayford's Text-book of Geodetic Astronomy 8vo, 3 00

Hering's Ready Reference Tables (Conversion Factors') i6mo, morocco, 2 50

Howe's Retaining Walls for Earth nmo, 1 25

* Ives's Adjustments of the Engineer's Transit and Level i6mo, Bds. 25

Ives and Hilts's Problems in Surveying i6mo, morocco, 1 50

Johnson's (J. B.) Theory and Practice of Surveying Small 8vo, 4 00

Johnson's (L. J.) Statics by Algebraic and Graphic Methods 8vo, 2 00

Laplace's Philosophical Essay on Probabilities. (Truscott and Emory.) . nmo, 2 00

Mahan's Treatise on Civil Engineering. (1873.) (Wood.) 8vo, 5 00

* Descriptive Geometry 8vo,

Merriman's Elements of Precise Surveying and Geodesy 8vo,

Merriman and Brooks's Handbook for Surveyors i6mo, morocco,

Nugent's Plane Surveying 8vo,

Ogden's Sewer Design i2mo,

Parsons's Disposal of Municipal Refuse 8vo,

Patton's Treatise on Civil Engineering 8vo half leather,

Reed's Topographical Drawing and Sketching 4to,

Rideal's Sewage and the Bacterial Purification of Sewage 8vo,

Siebert and Biggin's Modern Stone-cutting and Masonry 8vo,

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Smith'.; Manual ui Topographical Drawing. (McMillan.; 8vo, 2 50

Sondericker's Graphic Statics, with Applications to 1 russes. Beams, and Arches.

8vo, 2 00

Taylor and Thompson's Treatise on Concrete, Plain and Reinfoiced 8vo, 5 00

* Trautwir.e's Civil Engineer's Pocket-book i6mo, morocco, 5 00

Venable's Garbage Crematories in America 8vo, 2 00

Wait's Engineering and Architectural Jurisprudence 8vo 6 00

Sheep, 6 50
Law of Operations Preliminary to Construction in Engineering and Archi-
tecture 8vo, s 00

Sheep, 5 50

Law of Contracts 8vo, 3 00

Warren's Stereotomy — Problems in Stone-cutting 8vo, 2 50

Webb's Problems in the Use and Adjustment of Engineering Instruments.

i6mo, morocco, 1 25

Wilson's Topographic Surveying 8vo, 3 50

BRIDGES AND ROOFS.

Boiler's Practical Treatise on the Construction of Iron Highway Bridges. . 8vo, 2 00

* Thames River Bridge 4to, paper, 5 00

Burr's Course on the Stresses in Bridges and Roof Trusses, Arched Rihs, and

Suspension Bridges 8vo, 3 50

Burr and Falk's Influence Lines for Bridge and Roof Computations 8vo, 3 00

Design and Construction of Metallic Bridges 8vo 5 00

Du Bois's Mechanics of Engineering. Vol. II Small 4to, 10 co

Foster's Treatise on Wooden Trestle Bridges 4to, 5 00

Fowler's Ordinary Foundations 8vo, 3 50

Greene's Roof Trusses 8vo, 1 25

Bridge Trusses 8vo, 2 50

Arches in Wood, Iron, and Stone 8vo 2 50

Howe's Treatise on Arches 8vo, 4 00

Design of Simple Roof-trusses in Wood and Steel » 8vo, 2 00

Symmetrical Masonry Arches 8vo, 2 50

Johnson, Bryan, and Turneaure's Theory and Practice in the Designing of

Modern Framed Structures Small 4to, 10 00

Merriman and Jacoby's Text-book on Roofs and Bridges:

Part I. Stresses in Simple Trusses 8vo, 2 50

Part II. Graphic Statics 8vo, 2 50

Part III. Bridge Design 8vo, 2 50

Part IV. Higher Structures 8vo, 2 50

Morison's Memphis Bridge 4to, 10 00

Waddell's De Pontibus, a Pocket-book for Bridge Engineers. . i6mo, morocco, 2 00

* Specifications for Steel Bridges nmo, 50

Wright's Designing of Draw-spans. Two parts in one volume 8vo, 3 50

HYDRAULICS.

Barnes's Ice Formation 8vo, 3 00

Bazin's Experiments upon the Contraction of the Liquid Vein Issuing from

an Orifice. (Trautwine.) 8vo, 2 00

Bovey's Treatise on Hydraulics 8vof 5 00

Church's Mechanics of Engineering 8vo, 6 00

Diagrams of Mean Velocity of Water in Open Channels paper, 1 50

Hydraulic Motors 8vo, 2 00

Coffin's Graphical Solution of Hydrr.ulic Problems i6mo, morocco, 2 50

Flather's Dynamometers, and the Measurement of Power i2mo, 3 00

7

Folwell's Water-supply Engineering 8vo, 4 00

Frizell's Water-power 8vo, 5 00

Fuertes's Water and Public Health nmo, 1 50

Water-filtration Works i2mo, 2 50

Ganguillet and Kutter's General Formula for the Uniform Flow of Water in

Rivers and Other Channels. (Hering and Trautwine.) 8vo, 4 00

Hazen's Filtration of Public Water-supply 8vo, 3 00

Hazlehurst's Towers and Tanks for Water- works 8vo, 2 50

Herschel's 115 Experiments on the Carrying Capacity of Large, Riveted, Metal

Conduits 8vo, 2 00

Mason's Water-supply. (Considered Principally from a Sanitary Standpoint.)

8vo, 4 00

Merriman's Treatise on Hydraulics 8vo, 5 00

* Michie's Elements of Analytical Mechanics 8vo, 4 00

Schuyler's Reservoirs for Irrigation, Water-power, and Domestic Water-
supply Large 8vo, 5 00

* Thomas and Watt's Improvement of Rivers 4to, 6 00

Turneaure and Russell's Public Water-supplies 8vo, 5 00

Wegmann's Design and Construction of Dams 4to, 5 00

Water-supply of the City of New York from 1658 to 1895 4to, 10 00

Whipple's Value of Pure Water Large nmo, 1 00

Williams and Hazen's Hydraulic Tables 8vo, 1 50

Wilson's Irrigation Engineering Small 8vo, 4 00

Wolff's Windmill as a Prime Mover 8vo, 3 00

Wood's Turbines 8vo, 2 50

Elements of Analytical Mechanics 8vo, 3 00

MATERIALS OF ENGINEERING.

Baker's Treatise on Masonry Construction 8vo,

Roads and Pavements 8vo,

Black's United States Public Works Oblong 4to,

* Bovey's Strength of Materials and Theory of Structures 8vo,

Burr's Elasticity and Resistance of the Materials of Engineering 8vo,

Byrne's Highway Construction 8vo,

Inspection of the Materials and Workmanship Employed in Construction.

i6mo,

Church's Mechanics of Engineering 8vo,

Du Bois's Mechanics-of Engineering. Vol. I. Small 4to,

*Eckel's Cements, Limes, and Plasters 8vo,

Johnson's Materials of Construction Large 8vo,

Fowler's Ordinary Foundations 8vo,

Graves's Forest Mensuration 8vo,

* Greene's Structural Mechanics 8vo,

Keep's Cast Iron 8vo,

Lanza's Applied Mechanics 8vo,

Marten's Handbook on Testing Materials. (Henning.) 2 vols 8vo,

Maurer's Technical Mechanics 8vo,

Merrill's Stones for Building and Decoration 8vo,

Merriman's Mechanics of Materials 8vo,

* Strength of Materials i2mo,

Metcalf's Steel. A Manual for Steel-users i2mo,

Patton's Practical Treatise on Foundations 8vo,

Richardson's Modern Asphalt Pavements 8vo,

Richey's Handbook for Superintendents of Construction i6mo, mor., 4 00

* Ries's Clays: Their Occurrence, Properties, and Uses 8vo, 5 00

Rockwell's Roads and Pavements in France i2mo, 1 25

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Sabin's Industrial and Artistic Technology of Paints ard Varnish 8vo, 3 00

Smith's Materials of Machines. i2mo, 1 00

Snow's Principal Species of Wood 8vo, 3 50

Spalding's Hydraulic Cement nnw, 2 00

Text-book on Roads and Pavements i2mo, 2 00

Taylor and Thompson's Treatise on Concrete, Plain and Reinforced 8vo, 5 00

Thurston's Materials of Engineering. 3 Parts 8vo, 8 00

Part I. Non-metallic Materials of Engineering and Metallurgy 8vo, 2 00

Part II. Iron and Steel 8vo, 3 50

Part III. A Treatise on Brasses, Bronzes, and Other Alloys and their

Constituents 8vo, 2 50

Tillson's Street Pavements and Paving Materials 8vo, 4 00

Waddell's De Pontibus. (A Pocket-book for Bridge Engineers.) .. i6mo, mor., 2 00

* Specifications for Steel Bridges i2mo, 50

Wood's (De V.) Treatise on the Resistance of Materials, and an Appendix on

the Preservation of Timber 8vo, 2 00

Wood's (De V.) Elements of Analytical Mechanics 8vo, 3 00

Wood's (M. P.) Rustless Coatings: Corrosion and Electrolysis of Iron and

Steel 8vo, 4 00

RAILWAY ENGINEERING.

Andrew's Handbook for Street Railway Engineers 3x5 inches, morocco, 1 25

Berg's Buildings and Structures of American Railroads 4to, 5 00

Brook's Handbook of Street Railroad Location i6mo, morocco,

Butt's Civil Engineer's Field-book i6mo, morocco,

Crandall's Transition Curve i6mo, morocco,

Railway and Other Earthwork Tables 8vo,

Dawson's "Engineering" and Electric Traction Pocket-book. . i6mo, morocco,

Dredge's History of the Pennsylvania Railroad: (1879) Paper,

Fisher's Table of Cubic Yards Cardboard,

Godwin's Railroad Engineers' Field-book and Explorers' Guide. . . i6mo, mor.,
Hudson's Tables for Calculating the Cubic Contents of Excavations and Em-
bankments 8vo, 1 00

Molitor and Beard's Manual for Resident Engineers i6mo, 1 00

Nagle's Field Manual for Railroad Engineers i6mo, morocco, 3 00

Philbrick's Field Manual for Engineers i6mo, morocco, 3 00

Searles's Field Engineering i6mo, morocco, 3 00

Railroad Spiral i6mo, morocco, 1 50

Taylor's Prismoidal Formulae and Earthwork 8vo, 1 50

* Trautwine's Method of Calculating the Cube Contents of Excavations and

Embankments by the Aid of Diagrams 8vo, 2 00

The Field Practice of Laying Out Circular Curves for Railroads.

i2mo, morocco, 2 50

Cross-section Sheet Paper, 25

Webb's Railroad Construction i6mo, morocco, 5 00

Economics of Railroad Construction Large i2mo, 2 50

Wellington's Economic Theory of the Location of Railways Small 8vo, 5 00

DRAWING.

Barr's Kinematics of Machinery 8vo, 2 50

* Bartlett's Mechanical Drawing 8vo, 3 00

* " " " Abridged Ed 8vo, 1 5°

Coolidge's Manual of Drawing 8vo, paper, 1 00

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Coolidge and Freeman's Elements of General Drafting for Mechanical Engi-
neers Oblong 4to,

Durley's Kinematics of Machines 8vo,

Emch's Introduction to Projective Geometry and its Applications 8vo,

Hill's Text-book on Shades and Shadows, and Perspective. 8vo,

Jamison's Elements of Mechanical Drawing 8vo,

Advanced Mechanical Drawing 8vo,

Jones's Machine Design:

Part I. Kinematics of Machinery 8vo,

Part II. Form, Strength, and Proportions of Parts 8vo,

MacCord's Elements of Descriptive Geometry 8vo,

Kinematics ; or, Practical Mechanism 8vo,

Mechanical Drawing 4to,

Velocity Diagrams 8vo,

MacLeod's Descriptive Geometry Small 8vo,

* Mahan's Descriptive Geometry and Stone-cutting 8vo,

Industrial Drawing. (Thompson.) 8vo,

Moyer's Descriptive Geometry 8vo, 2 00

Reed's Topographical Drawing and Sketching 4to, 5 00

Reid's Course in Mechanical Drawing 8vo, 2 00

Text-book of Mechanical Drawing and Elementary Machine Design. 8vo, 3 00

Robinson's Principles of Mechanism ; . . . 8vo, 3 00

Schwamb and Merrill's Elements of Mechanism 8vo, 3 00

Smith's (R. S.) Manual of Topographical Drawing. (McMillan.) 8vo, 2 50

Smith (A. W.) and Marx's Machine Design 8vo, 3 00

* Titsworth's Elements of Mechanical Drawing Oblong 8vo, 1 25

Warren's Elements of Plane and Solid Free-hand Geometrical Drawing. i2mo, 1 00

Drafting Instruments and Operations i2mo, 1 25

Manual of Elementary Projection Drawing i2mo, 1 50

Manual of Elementary Problems in the Linear Perspective of Form and

Shadow i2mo, 1 00

Plane Problems in Elementary Geometry i2mo, 1 25

Primary Geometry. i2mo, 75

Elements of Descriptive Geometry, Shadows, and Perspective 8vo, 3 50

General Problems of Shades and Shadows 8vo, 3 00

Elements of Machine Construction and Drawing 8vo, 7 50

Problems, Theorems, and Examples in Descriptive Geometry 8vo, 2 50

Weisbach's Kinematics and Power of Transmission. (Hermann and

Klein.) 8vo, 5 00

Whelpley's Practical Instruction in the Art of Letter Engraving nmo, 2 00

Wilson's (H. M.) Topographic Surveying 8vo, 3 50

Wilson's (V. T.) Free-hand Perspective 8vo. 2 50

Wilson's (V. T.) Free-hand Lettering 8vo, 1 00

Woolf's Elementary Course in Descriptive Geometry Large 8vo, 3 00

ELECTRICITY AND PHYSICS.

* Abegg's Theory of Electrolytic Dissociation. (Von Ende.) i2mo, 1 25

Anthony and Brackett's Text-book of Physics. (Magie.) Small 8vo 3 00

Anthony's Lecture-notes on the Theory of Electrical Measurements. . . . i2mo, 1 00

Benjamin's History of Electricity 8vo, 3 00

Voltaic Cell 8vo, 3 00

Classen's Quantitative Chemical Analysis by Electrolysis. (Boltwood.).8vo, 3 00

* Collins's Manual of Wireless Telegraphy i2mo, 1 50

Morocco, 2 00

Crehore and Squier's Polarizing Photo-chronograph 8vo, 3 00

* Danneel's Electrochemistry. (Merriam.) i2mo, 1 25

Dawson's "Engineering" and Electric Traction Pocket-book. i6mo, morocco, 5 00

10

Dolezalek's Theory of the Lead Accumulator ( Storage Battery). 'Von

Ende.) i2mo, 2 50

Duhem's Thermodynamics and Chemistry. (Burgess.) 8vo, 4 00

Flather's Dynamometers, and the Measurement of Power i2mo, 3 00

Gilbert's De Magnete. (Mottelay. ) 8vo, 2 50

Hanchett's Alternating Currents Explained i2mo, 1 00

Hering's Ready Reference Tables (Conversion Factors) i6mo morocco, 2 50

Holman's Precision of Measurements 8vo, 2 00

Telescopic Mirror-scale Method, Adjustments^ and Tests. .. .Large 8vo, 75

Kinzbrunner's Testing of Continuous-current Machines 8vo, 2 00

Landauer's Spectrum Analysis. (Tingle.) 8vo, 3 00

Le Chatelier s High-temperature Measurements. (Boudouard — Burgess.) i2mo, 3 00

Lc'ib's Electrochemistry of Organic Compounds. (Lorenz. ) 8vo, 3 00

* Lyons'? Treatise on Electromagnetic Phenomena. Vols. I. and II. 8vo, each, 6 00

* Michie's Elements of Wave Motion Relating to Sound and Light 8vo, 4 00

Niaudet's Elementary Treatise on Electric Batteries. (Fishback.) i2mo, 2 50

* Parshall and Hobart's Electric Machine Design 4to, half morocco, 12 50

Reagan's Locomotives: Simple, Compound, and Electric. New Edition.

Large nmo, 3 50

* Rosenberg's Electrical Engineering. (Haldane Gee — Kinzbrunner.). . .8vo, 2 00

Ryan, Norris, and Hoxie's Electrical Machinery. Vol. 1 8vo, 2 50

Thurston's Stationary Steam-engines 8vo, 2 5«

* Tillman's Elementary Lessons in Heat 8vo, 1 50

Tory and Pitcher's Manual of Laboratory Physics Small 8vo, 2 00

Ulke's Modern Electrolytic Copper Refining 8vo, 3 00

LAW.

* Davis's Elements of Law 8vo,

* Treatise on the Military Law of United States 8vo,

* Sheep,

* Dudley's Military Law and the Procedure of Courts-martial . . .Large nmo,

Manual for Courts-martial. i6mo, morocco,

Wait's Engineering and Architectural Jurisprudence 8vo,

Sheep,
Law of Operations Preliminary to Construction in Engineering and Archi-
tecture 8vo

Sheep,

Law of Contracts 8vo,

Winthrop's Abridgment of Military Law i2mo,

MANUFACTURES.

Bernadou'S Smokeless Powder — Nitro-cellulose and Theory of tte Cellulose

Molecule i2mo,

Bolland's Iron Founder nmo,

The Iron Founder," Supplement 1 2mo,

Encyclopedia of Founding and Dictionary of Foundry Terms Used in the
Practice of Moulding i2mo,

* Claassen's Beet-sugar Manufacture. (Hall and Rolfe.) 8vo,

* Eckel's Cements, Limes, and Plasters , 8vo,

Eissler's Modern High Explosives 8vo,

Effront's Enzymes and their Applications. (Prescott.) 8vo,

Fitzgerald's Boston Machinist i2mo,

Ford's Boiler Making for Boiler Makers i8mo,

Hopkin's Oil-chemists' Handbook 8vo,

Keep's Cast Iron 8vo,

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Leach's The Inspection and Analysis of Food with Special Reference to State

Control. Large 8vo, 7 50

* McKay and Larsen's Principles and Practice of Butter-making 8vo, 1 50

Matthews's The Textile Fibres 8vo, 3 50

Metcalf's Steel. A Manual for Steel-users: nmo, 2 00

Metcalfe'f Cost of Manufactures — And the Administration of Workshops. 8vo, 5 00

Meyer's Modern Locomotive Construction 4to, 10 00

Morse's Calculations used in Cane-sugar Factories i6mo, morocco, 1 50

* Reisig's Guide to Piece-dyeing 8vo, 25 00

Rice's Concrete-block Manufacture 8vo, 2 00

Sabin's Industrial and Artistic Technology of Paints and Varnish 8vo,

Smith's Press-working of Metals 8vo,

Spalding's Hydraulic Cement i2mo,

Spencer's Handbook for Chemists of Beet-sugar Houses. .... i6mo morocco,

Handbook for Cane Sugar Manufacturers i6mo morocco,

Taylor and Thompson's Treatise on Concrete, Plain and Reinforced 8vo,

Thurston's Manual of Steam-boilers, their Designs, Construction and Opera-
tion 8vo,

* Walke's Lectures on Explosives 8vo,

Ware's Beet-sugar Manufacture and Refining Small 8vo,

Weaver's Military Explosives 8vo,

West's American Foundry Practice i2mo,

Moulder's Text-book i2mo,

Wolff's Windmill as a Prime Mover 8vo,

Wood's Rustless Coatings: Corrosion and Electrolysis of Iron and Steel. .8vo,

MATHEMATICS.

Baker's Elliptic Functions. t. 8vo, 1 50

* Bass's Elements of Differential Calculus. i2mo, 4 00

Briggs's Elements of Plane Analytic Geometry i2mo, 1 00

Compton's Manual of Logarithmic Computations i2mo 1 50

Davis's Introduction to the Logic of Algebra 8vo, 1 50

* Dickson's College Algebra Large i2mo, 1 50

* Introduction to the Theory of Algebraic Equations. Large i2mo, 1 25

Emch's Introduction to Projective Geometry and its Applications 8vo 2 50

Halsted's Elements of Geometry 8vo, 1 75

Elementary Synthetic Geometry. 8vo, 1 50

Rational Geometry i2mo, 1 75

* Johnson's (J. B.) Three-place Logarithmic Tables: Vest-pocket size. paper, 15

100 copies for 5 00

* Mounted on heavy cardboard, 8X 10 inches, 25

10 copies for 2 00

Johnson's (W. W.) Elementary Treatise on Differential Calculus . . Small 8vo, 3 00

Elementary Treatise on the Integral Calculus SmalI*8vo, 1 50

Johnson's (W. W.) Curve Tracing in Cartesian Co-ordinates. i2mo, 1 00

Johnson's (W. W.) Treatise on Ordinary and Partiar Differential Equations.

Small 8vo, 3 50

Johnson's (W, W.) Theory of Errors and the Method of Least Squares, nmo, 1 50

* Johnson's (W W.) Theoretical Mechanics i2mo, 3 00

Laplace's Philosophical Essay on Probabilities. (Truscott and Emory.). i2mo, 2 00

* Ludlow and Bass. Elements of Trigonometry and Logarithmic and Other

Tables 8vo, 3 00

Trigonometry and Tables published separately Each, 2 oc

* Ludlow's Logarithmic and Trigonometric Tables. 8vo 1 00

Manning's Irrational Numbers and their Representation by Sequences and Series

i2mo, 1 25

12

Mathematical Monographs. Edited by Mansfield Merriman and Robert

S. Woodward. Octavo, each I oo

No. i. History of Modern Mathematics, by David Eugene Smith.
No. 2. Synthetic Projective Geometry, by George Bruce Halsted.
No. 3. Determinants, by Laenas Gifford Weld. No. 4. Hyper-
bolic Functions, by James McMahon. No. 5. Harmonic Func-
tions, by William E. Byerly. No. 6. Grassmann's Space Analysis,
by Edward W. Hyde. No. 7. Probability and Theory of Errors,
by Robert S. Woodward. No. 8. Vector Analysis and Quaternions,
by Alexander Macfarlane. No. q. Differential Equations, by
William Woolsey Johnson. No. 10. The Solution of Equations,
by Mansfield Merriman. No. n. Functions of a Complex Variable,
by Thomas S. Fiske.

Maurer's Technical Mechanics 8vo, 4 00

Merriman's Method of Least Squares 8vo, 2 00

Rice and Johnson's Elementary Treatise on the Differential Calculus. . Sm. 8vo, 3 00

Differential and Integral Calculus. 2 vols, in one Small 8vo, 2 50

* Veblen and Lennes's Introduction to the Real Infinitesimal Analysis of One

Variable 8vo, 2 00

Wood's Elements of Co-ordinate Geometry 8vo, 2 00

Trigonometry: Analytical, Plane, and Spherical i2mo, 1 00

MECHANICAL ENGINEERING.

MATERIALS OF ENGINEERING, STEAM-ENGINES AND BOILERS.

Bacon's Forge Practice i2mo, 1 50

Baldwin's Steam Heating for Buildings i2mo, 2 50

Barr's Kinematics of Machinery 8vo, 2 50

* Bartlett's Mechanical Drawing 8vo, 3 00

* " " Abridged Ed 8vo, 1 50

Benjamin's Wrinkles and Recipes nmo, 2 00

Carpenter's Experimental Engineering 8vo,

Heating and Ventilating Buildings 8vo,

Clerk's Gas and Oil Engine Small 8vo,

Coolidge's Manual of Drawing 8vo, paper,

Coolidge and Freeman's Elements of General Drafting for Mechanical En-
gineers Oblong 4to,

Cromwell's Treatise on Toothed Gearing i2mo,

Treatise on Belts and Pulleys i2mo,

Durley's kinematics of Machines 8vo,

Flather's Dynamometers and the Measurement of Power 1 21110,

Rope Driving nmo,

Gill's Gas and Fuel Analysis for Engineers nmo,

Hall's Car Lubrication i2mo,

Herintr's Ready Reference Tables (Conversion Factors') i6mo, morocco,

Hutton's The Gas Engine 8vo,

Jamison's Mechanical Drawing 8vo,

Jones's Machine Design:

Part I. Kinematics of Machinery 8vo,

Part II. Form, Strength, and Proportions of Parts 8vo,

Kent's Mechanical Engineers' Pocket-book i6mo, morocco,

Kerr's Power and Power Transmission 8vo,

Leonard's Machine Shop, Tools, and Methods 8vo,

* Lorenz's Modern Refrigerating Machinery. ( Pope, Haven, and Dean.) . . 8vo,
MacCord's Kinematics; cr. Practical Mechanism 8vo,

Mechanical Drawing 4to,

Velocity Diagrams 8vo,

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MacFarland's Standard Reduction Factors for Gases 8vo, i 50

Hahan's Industrial Drawing. (Thompson.) 8vo 3 50

Pooies Calorific Power of Fuels 8vo, 3 00

Reid's Course in Mechanical Drawing 8vo, 2 00

Text-book of Mechanical Drawing and Elementary Machine Design. 8vo, 3 00

Richard's Compressed Air i2mo, 1 50

Robinson's Principles of Mechanism 8vo, 3 00

Scb.war.ib and Merrill's Elements of Mechanism 8vo, 3 00

Smith's (O.) Press-working of Metals 8vo 3 co

Smith (A. W.) and Marx's Machine Design 8vo, 3 00

Thurston's Treatise on Friction and Lost Work in Machinery and Mill

Work 8vo» 3 00

Animal as a Machine and Prime Motor, and the Laws of Energetics. i2mo, 1 00

Tillson's Complete Automobile Instructor i6mo, 1 50

Morocco, 2 00

Warren's Elements of Machine Construction and Drawing 8vo, 7 50

Weisbacb's Kinematics and the Power of Transmission. (Herrmann —

Klein.) 8vo, 5 00

Machinery of Transmission and Governors. (Herrmann — Klein.). .8vo, 5 00

Wolff's Windmill as a Prime Mover 8vo, 3 00

Wood's Turbines 8vo, 2 50

MATERIALS OF ENGINEERING.

* Bovey's Strength of Materials and Theory of Structures 8vo,

Burr's Elasticity and Resistance of the Materials of Engineering. 6th Edition.

Reset 8vo,

Church's Mechanics of Engineering 8vo,

* Greene's Structural Mechanics <?vo,

Johnson's Materials of Construction 8vo,

Keep's Cast Iron 8vo,

Lanza's Applied Mechanics 8vo,

Martens's Handbook on Testing Materials. (Henning.) 8vo,

Maurer's Technical Mechanics 8vo,

Merriman's Mechanics of Materials 8vo,

* Strength of Materials i2mo,

Metcalf 's Steel. A Manual for Steel-users i2mo,

Sabin's Industrial and Artistic Technology of Paints and Varnish 8vo,

Smith's Materials of Machines i2mo,

Thurston's Materials of Engineering 3 vols., 8vo,

Part II. Iron and Steel 8vo,

Part III. A Treatise on Brasses, Bronzes, and Other Alloys and their

Constituents 8vo, 2 50

Wood's (De V.) Treatise on the Resistance of Materials and an Appendix on

the Preservation of Timber 8vo, 2 00

Elements of Analytical Mechanics 8vo, 3 00

Wood's (M. P.) Rustless Coatings: Corrosion and Electrolysis of Iron and

Steel 8vo, 4 00

STEAM-ENGINES AND BOILERS.

Berry's Temperature-entropy Diagram i2mo, 1 25

Carnot's Reflections on the Motive Power of Heat. (Thurston.) i2mo, 1 50

Dawson's " Engineering " and Electric Traction Pocket-book. . . . i6mo, mor., 5 00

Ford's Boiler Making for Boiler Makers i8mo, 1 00

Goss's Locomotive Sparks 8vo, 2 00

Locomotive Performance 8vo, 5 00

Hemenway's Indicator Practice and Steam-engine Economy 121110, 2 00

14

7

50

6

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6

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2

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7

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7

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4

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1

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2

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1

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8

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3

50

Hutton's Mechanical Engineering of Power Plants 8vo, 5 00

Heat and Heat-engines 8vo 5 00

Kent's Steam boiler Economy 8vo, 4 00

Kneass's Practice and Theory of the Injector 8vo, 1 50

MacCord's Slide-valves 8vo, 2 00

Meyer's Modern Locomotive Construction 4to, 10 00

Peabody's Manual of the Steam-engine Indicator i2mo, 1 50

Tables of the Properties of Saturated Steam and Other Vapors 8vo, 1 00

Thermodynamic of the Steam-engine and Other Heat-engines 8vo, 5 00

Valve-gears for Steam-engines 8vo, 2 50

Peabody and Miller's Steam-boilers 8vo, 4 00

Pray's Twenty Years with the Indicator Large 8vo, 2 5c

Pupin's Thermodynamics of Reversible Cycles in Gases and Saturated Vapors.

(Osterberg.) i2mo, 1 25

Reagan's Locomotives: Simple, Compound, and Electric. New Edition.

Large i2mo, 3 -o

Rontgen's Principles of Thermodynamics. (Du Bois.) 8vo, 5 o«

Sinclair's Locomotive Engine Running and Management i2mo, 2 00

Smart's Handbook of Engineering Laboratory Practice nmo, 2 50

Snow's Steam-boiler Practice 8vo, 3 00

Spangler's Valve-gears 8vo, 2 50

Notes on Thermodynamics 1 2mo, 1 00

Spangler, Greene, and Marshall's Elements of Steam-engineering 8vo, 3 00

Thomas's Steam-turbines 8vo, 3 50

Thurston's Handy Tables 8vo, 1 50

Manual of the Steam-engine 2 vols., 8vo, 10 00

Part I. History, Structure, and Theory 8vo, 6 00

Part II. Desisn, Construction, and Operation 8vo, 6 00

Handbook of Engine and Boiler Trials, and the Use of the Indicator and

the Prony Brake 8vo, 5 00

Stationary Steam-engines 8vo, 2 50

Steam-boiler Explosions in Theory and in Practice nmo, 1 50

Manual of Steam-boilers, their Designs, Construction, and Operation. 8vo, 5 00

Wehrenfenning's Analysis and Softening of Boiler Feed-water (Patterson) 8vo, 4 00

Weisbach's Heat, Steam, and Steam-engines. (Du Bois.) 8vo, 5 00

Whitham's Steam-engine Design 8vo, 5 00

Wood's Thermodynamics, Heat Motors, and Refrigerating Machines. ..8vo, 4 00

MECHANICS AND MACHINERY.

Barr's Kinematics of Machinery 8vo, 2 50

* Bovey's Strength of Materials and Theory of Structures 8vo, 7 50

Chase's The Art of Pattern-making l2mo, 2 50

Church's Mechanics of Engineering 8vo, 6 00

Notes and Examples in Mechanics 8vo, 2 00

Compton's First Lessons in Metal-working i2mo, 1 50

Compton and De Groodt's The Speed Lathe i2mo, 1 50

Cromwell's Treatise on Toothed Gearing nmo, 1 50

Treatise on Belts and Pulleys i2mo, 1 50

Dana's Text-book of Elementary Mechanics for Colleges and Schools. ,i2mo, 1 50

Dingey's Machinery Pattern Making i2mo, 2 00

Dredge's Record of the Transportation Exhibits Building of the World's

Columbian Exposition of 1893 4to half morocco, 5 00

Du Bois's Elementary Principles of Mechanics:

Vol. I. Kinematics 8vo, 3 50

Vol. II. Statics 8vo. 4 00

Mechanics of Engineering. Vol. I Small 4to, 7 50

Vol. II Small 4to, 10 00

Durley's Kinematics of Machines 8vo, 4 00

15

Fitzgerald's Boston Machinist i6mo, i oo

Flather's Dynamometers, and the Measurement of Power i2mo, 3 00

Rope Driving i2mo, 2 00

Goss's Locomotive Sparks 8vo, 2 00

Locomotive Performance 8vo, 5 00

* Greene's Structural Mechanics 8vo, 2 50

Hall's Car Lubrication i2mo, 1 00

Holly's Art of Saw Filing i8mo, 75

James's Kinematics of a Point and the Rational Mechanics of a Particle.

Small 8vo, 2 00

* Johnson's (W. W.) Theoretical Mechanics i2mo, 3 00

Johnson's (L. J.) Statics by Graphic and Algebraic Methods 8vo, 2 00

Jones's Machine Design:

Part I. Kinematics of Machinery 8vo, 1 50

Part II. Form, Strength, and Proportions of Parts 8vo, 3 00

Kerr's Power and Power Transmission 8vo, 2 00

Lanza's Applied Mechanics 8vo, 7 50

Leonard's Machine Shop, Tools, and Methods 8vo, 4 00

* Lorenz's Modern Refrigerating Machinery. (Pope, Haven, and Dean.). 8vo, 4 00
MacCord's Kinematics; or, Practical Mechanism 8vo, 5 00

Velocity Diagrams 8vo, 1 50

* Martin's Text Book on Mechanics, Vol. I, Statics i2mo, 1 25

Maurer's Technical Mechanics 8vo, 4 00

Merriman's Mechanics of Materials 8vo, 5 00

* Elements of Mechanics i2mo, 1 00

* Michie's Elements of Analytical Mechanics 8vo, 4 00

* Parshall and Hobart's Electric Machine Design 4T0, half morocco, 12 50

Reagan's Locomotives : Simple, Compound, and Electric. New Edition.

Large i2mo, 3 00

Reid's Course in Mechanical Drawing 8vo, 2 00

Text-book of Mechanical Drawing and Elementary Machine Design. 8vo, 3 00

Richards's Compressed Air i2mo, 1 50

Robinson's Principles of Mechanism 8vo, 3 00

Ryan, Norris, and Hoxie's Electrical Machinery. Vol. 1 8vo, 2 50

Sanborn's Mechanics: Problems Large i2mo, 1 50

Schwamb and Merrill's Elements of Mechanism 8vo, 3 00

Sinclair's Locomotive-engine Running and Management i2mo, 2 00

Smith's (O.) Press-working of Metals 8vo, 3 00

Smith's (A. W.) Materials of Machines nmo, 1 00

Smith (A. W.) and Marx's Machine Design 8vo, 3 00

Spangler, Greene, and Marshall's Elements of Steam-engineering.: 8vo, 3 00

Thurston's Treatise on Friction and Lost Work in Machinery and Mill

Work 8vo, 3 00

Animal as a Machine and Prime Motor, and the Laws of Energetics. 1 2mo , 1 00

Tillson's Complete Automobile Instructor i6mo, 1 50

Morocco, 2 00

Warren's Elements of Machine Construction and Drawing 8vo, 7 50

Weisbach's Kinematics and Power of Transmission. (Herrmann — Klein. ) . 8vo, 5 00

Machinery of Transmission and Governors. (Herrmann — Klein. ).8vo, 5 00

Wood's Elements of Analytical Mechanics 8vo, 3 00

Principles of Elementary Mechanics i2mo, 1 25

Turbines 8vo, 2 50

The World's Columbian Exposition of 1893 4to, 1 00

MEDICAL.

De Fursac's Manual of Psychiatry. (Rosanoff and Collins.) Large i2mo, 2 50

Ehrlich's Collected Studies on Immunity. (Bolduan.) 8vo, 6 00

Hammarsten's Text-book on Physiological Chemistry. (Mandel.) 8vo, 4 00

16

Lassar-Cohn's Practical Urinary Analysis. CLorenz.) i2n-.o, i oo

* Pauli's Physical Chemistry in the Service of Medicine. (Fischer, i i2mo, i 35

* Pozzi-Escot's The Toxins and Venoms and their Antibodies. (Cohn. 1. i2mo, 1

Rostoski's Serum Diagnosis. (Bolduan.) i2mo, 1 00

Salkowski's Physiological and Pathological Chemistry. (Orndorff.). . 8*vo, 2 50

* Satterlee's Oatlines of Human Embryology i2mo, 1 25

Steel's Treatise on the Diseases of the Dog 8vo, 3 50

Von Behring's Suppression of Tuberculosis. (Bolduan.) i2mo, 1 00

Wassermann's Immune Sera1 Haemolysis, Cytotoxins, and Precipitins. ( Bol-
duan.1 i2mo,cloth, 1 00

Woodhull's Notes on Military Hygiene i6mo, 1 50

* Personal Hygiene i2mo, 1 00

Wulling's An Elementary Course in Inorganic Pharmaceutical and Medical

Chemfstry nmo, 2 00

METALLURGY.

Egleston's Metallurgy of Silver, Gold, and Mercury:

Vol. I. Silver 8vo, 7 50

Vol. II. Gold and Mercury 8vo, 7 50

Goesel's Minerals and Metals: A Reference Book i6mo, mor. 3 00

* Iles's Lead-smelting i2mo, 2 50

Keep's Cast Iron 8vo, 2 50

Kunhardt's Practice of Ore Dressing in Europe 8vo, 1 50

Le Chatelier's High-temperature Measurements. (Boudouard — Burgess.") 12 mo, 3 00

Metcalf's SteeL A Manual for Steel-users i2mo, 2 00

Miller's Cyanide Process i2mo, 1 00

Minet's Production of Aluminum and its Industrial Use. (Waldo.). ... i2mo, 2 50

Robine and Lenglen's Cyanide Industry. (Le Clerc.) 8vo, 4 00

Smith's Materials of Machines i2mo, 1 00

Thurston's Materials of Engineering. In Three Parts 8vo, 8 00

Part II. Iron and Steel 8vo, 3 50

Part III. A Treatise on Brasses, Bronzes, and Other Alloys and their

Constituents 8vo, 2 50

Ulke's Modern Electrolytic Copper Refining 8vo, 3 00

MINERALOGY.

Barringer's Description of Minerals of Commercial Value. Oblong, morocco, 2 50

Boyd's Resources of Southwest Virginia 8vo, 3 00

Map of Southwest Virignia. Pocket-book form. 2 00

Brush's Manual of Determinative Mineralogy. (Penfield.) 8vo, 4 00

Chester's Catalogue of Minerals 8vo, paper, 1 00

Cloth, i 25

Dictionary of the Names of Minerals 8vo, 3 50

Dana's System of Mineralogy Large 8vo, half leather, 12 50

First Appendix to Dana's New " System of Mineralogy." Large 8vo, 1 00

Text-book of Mineralogy 8vo, 4 00

Minerals and How to Study Them i2mo. 1 50

Catalogue of American Localities of Minerals Large 8vo, 1 00

Manual of Mineralogy and Petrography i2mo 2 00

Douglas's Untechnical Addresses on Technical Subjects i2mo, 1 00

Eakle's Mineral Tables 8vo, 1 25

Egleston's Catalogue of Minerals and Synonyms 8vo, 2 50

Goesel's Minerals and Metals : A Reference Book 1 Ohio, mor. 3 00

Groth's Introduction to Chemical Crystallography (Marshall) i2mo, 1 25

17

Iddings's Rock Minerals 8vo, 5 00

Merrill's Non-metallic Minerals: Their Occurrence and Uses 8vo, 4 00

* Penfield's Notes on Determinative Mineralogy and Record of Mineral Tests.

8vo, paper, 50

* Richards's Synopsis of Mineral Characters i2mo, morocco, 1 25

* Ries's Clays: Their Occurrence, Properties, and Uses 8vo, 5 00

Rosenbusch's Microscopical Physiography of the Rock-making Minerals.

(Iddings.) 8vo, 5 00

* Tillman's Text-book of Important Minerals and Rocks 8vo, 2 00

MINING.

Boyd's Resources of Southwest Virginia 8vo, 3 00

Map of Southwest Virginia Pocket-book form 2 00

Douglas's Untechnical Addresses on Technical Subjects i2mo, I 00

Eissler's Modern High Explosives. ... R~~> 4 ">i

Goesel's Minerals and Metals : A Reference Book i6mo,mor. 300

Goodyear's Coal-mines of the Western Coast of the United States i2mo, 2 50

Ihlseng's Manual of Mining 8vo, 5 00

* Iles's Lead-smelting nmo, 2 50

Kunhardt's Practice of Ore Dressing in Europe 8vo, 1 50

Miller's Cyanide Process i2mo, 1 00

O'Driscoll's Notes on the Treatment of Gold Ores 8vo, 2 00

Robine and Lenglen's Cyanide Industry. (Le Clerc.) 8vo, 4 00

* Walke's Lectures on Explosives 8vo, 4 00

Weaver's Military Explosives 8vo, 3 00

Wilson's Cyanide Processes i2mo, 1 50

Chlorination Process i2mo, 1 50

Hydraulic and Placer Mining nmo, 2 00

Treatise on Practical and Theoretical Mine Ventilation i2mo, 1 25

SANITARY SCIENCE.

Bashore's Sanitation of a Country House nmo, 1 00

* Outlines of Practical Sanitation nmo, 1 25

Folwell's Sewerage. (Designing, Construction, and Maintenance.) 8vo, 3 00

Water-supply Engineering. 8vo, 4 00

Fowler's Sewage Works Analyses nmo, 2 00

Fuertes's Water and Public Health nmo, 1 50

Water-filtration Works nmo, 2 50

Gerhard's Guide to Sanitary House-inspection i6mo, 1 00

Hazen's Filtration of Public Water-supplies 8vo, 3 00

Leach's The Inspection and Analysis of Food with Special Reference to State

Control 8vo,

Mason's Water-supply. ( Considered principally from a Sanitary Standpoint) 8vo,

Examination of Water. (Chemical and Bacteriological.) nmo,

* Merriman's Elements of Sanitary Engineering 8vo,

Ogden's Sewer Design nmo,

Prescott and Winslow's Elements of Water Bacteriology, with Special Refer-
ence to Sanitary Water Analysis nmo,

* Price's Handbook on Sanitation nmo,

Richards's Cost of Food. A Study in Dietaries nmo,

Cost of Living as Modified by Sanitary Science nmo,

Cost of Shelter nmo,

18

7

50

4

00

1

25

2

00

2

00

1

25

1

5<*

Richards and Woodman's Air. Water, and Food from a Sanitary Stand-
point 8vo, 2 oo

* Richards and Williams's The Dietary Computer 8vo. i 50

Rideal's Sewage and Bacterial Purification of Sewage 8vo, 4 00

Turneaure and Russell's Public Water-supplies 8vo, 5 00

Von Behring's Suppression of Tuberculosis. (Bolduan.) i2mo, 1 00

Whipple's Microscopy of Drinking-water 8vo, 3 50

Winton's Microscopy of Vegetable Foods 8vo, 7 50

Woodhull's Notes on Military Hygiene i6mo, 1 50

* Personal Hygiene i2mo, 1 00

MISCELLANEOUS.

Emmons's Geological Guide-book of the Rocky Mountain Excursion of the

International Congress of Geologists Large 8vo, 1 50

Ferrel's Popular Treatise en the Winds 8vo, 4 00

Gannett's Statistical Abstract of the World 24010, 75

Haines's American Railway Management i2mo, 2 50

Ricketts's Eistory of Rensselaer Polytechnic Institute, 1 824-1 894. .Small 8 vo, 3 00

Rotherham's Emphasized New Testament Large 8vo . 2 00

The World's Columbian Exposition of 1893 4to, 1 00

Winslow's Elements of Applied Microscopy nmo, 1 50

HEBREW AND CHALDEE TEXT-BOOKS.

Green's Elementary Hebrew Grammar nmo, 1 25

Hebrew Chrestomathy 8vo, 2 00

Gesenius's Hebrew and Chaldee Lexicon to the Old Testament Scriptures.

(Tregelles.) Small 4to, half morocco, 5 00

Letteris's Hebrew Bible 8vo, 2 25

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