Albert P. Mathews.

Physiological chemistry: a text-book and manual for students online

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is generally — 0.571°, the juice is generally hypertonic, not hypotonic,
to the blood. The secretion of the gastric juice raises the concentration
of the blood when the juice is discharged to the exterior through a fistula.

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Thus in an experiment of Bosemann the freezing point of the blood
before secretion was — 0.589° and after — 0.600°. The dry residue is
0.26-0.653 per cent. The ash was 0.133 per cent. (0.105-0.204 per cent.).
The organic matter varied from 0.176-0.434. The ash contained iron,
calcium and phosphoric acid, and the usual salts of blood serum. The
organic substance gives both the Millon and biuret test, although Madame
Schumova-Simonowski stated that it did not give the biuret test when
it was perfectly fresh, but only after standing. Ammonium chloride is
present only in small amounts. There was no lactic acid. The acidity
computed as hydrochloric acid was from 0.46-0.58 per cent. The juice
contained, as a mean, 0.6137 per cent, of chlorine. Of this 0.5322 per
cent, was present in hydrochloric acid ; 0.0653 per cent, was in the ash
as chlorides ; and the remainder was 0.0162 organically combined. Since
the per cent, of chlorine in dog's blood is 0.295-0.275 per cent., the
gastric juice is twice as concentrated in chlorine as the blood. During
secretion, therefore, on one side of the mucous membrane the concen-
tration of the chlorine is 0.54-0.64 per cent ; on the other, 0.41 per cent,
in the plasma; and in the membrane itself 0.09 per cent.

The hydrogen ion concentration of pure human gastric juice from a
case of stomach fistula was found by Dr. Menten in the author's labo-
ratory, using the gas-chain method, to be about equivalent to that of
N/10 HC1, or even a little more acid than this. In the stomach, how-
ever, the juice is generally mixed with food substances so that its acidity
is lower than this. See page 368.

Composition of Gastric Juice.

Dog (Bosemann) Human (Bidder and Schmidt)

Water 99.74 - 99.36 Water 99.44

Dry residue 0.26 - 0.64 Organic 32

Organic 0.17- 0.43 HC1 0.20

Inorganic 0.10 - 0.21 CaCl 2 0.0061

Hydrochloric acid 0.46 - 0.58 NaCl 0.146

Chlorine 0.61 KC1 0.055

Chlorine in HC1 0.53 NH CI

Chlorine in chlorides . . 0.077 Ca (PO )

Chlorine in organic 0.016 Mg (PO ) I 0.0125

Ash 0.127 PeW 4

Water sol. ash 0.120 Human Appetite Jnlce (Carlson)

Na 0.025 Sp. gravity 1007

K 0.030 Total acidity ... 0.45 -0.50

CI " . '. 0.067 Freezing point . . 0.580 - 0.530

S0 8 0.0012 Total solids .... 0.48 - 0.61%

Insol. ash 0.0023 Organic 0.34 - 0.47

Ca 0.00022 Inorganic 0.11 -0.14

Mg 0.00022 Free acidity .... 0.35 - 0.45

P 2 B 0.0006 Total chlorine... 0.49 -0.56%

*e Trace NH 3 0.051 - 0.074%

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Amount of gastric juice secreted. — The amount of juice secreted
is subject to great variations, depending on the amount of food eaten,
the state of health and so on. By means of the small stomach pouch just
described Pawlow found that the amount secreted by the small stomach
was directly proportional to the amount of food eaten. If he doubled
the size of a meal, the amount of juice was doubled. This proportion-
ality is of course true only within limits. It was estimated by Bidder
and Schmidt that in human beings 2-3 liters of gastric juice were secreted
per day, and this is probably not far from the truth. In an experiment
by Rosemann the stomach of a large dog weighing 24,100 grams secreted
during a sham feeding in the first two hours at the rate of 200-300 c.c.
per hour; it then fell to 100 c.c. per hour. It was found by Pawlow
that when food entered the stomach the secretion was larger than when
there was only a sham feeding. We may, perhaps, estimate that in this
dog at least 500 c.c. of juice would be secreted for the digestion of each
meal. If a man's stomach secretes at the same rate, this would give
about 1,500 c.c. for the digestion of a meal.

In these fistula dogs the amount of chlorine and water secreted in
the juice may form a very considerable proportion of that contained
in the whole body. Thus in the dog experiment just quoted the total
amount of juice secreted in the sham feeding in 2% hours amounted to
one-half the total volume of the blood in the body. The secretion of this
amount of liquid caused great thirst. In various researches Rosemann
found the total chlorine secreted in. 3^4 hours to be from 4.4-5.5 grams.
In a dog weighing 26 kilos there are in the blood about 5.4 grams of
chlorine, so that as much chlorine was secreted in the gastric juice as
the total amount present in the blood. Such a loss of chlorine would
almost certainly affect the activities of all the cells of the body. The
total chlorine in the body of a dog of this weight was estimated as 20.8
grams, so that approximately one-fourth of it was eliminated by the
gastric juice in three hours.

The gastric juice of human beings contains on the average about 0.3
per cent, of hydrochloric acid; that of dogs about 0.53 per cent. If a
liter or 1,500 c.c. of such juice is secreted in each person for the diges-
tion of a meal, this would mean the secretion of from three to five grams
of hydrochloric acid each meal time. Since this acid is poured out
before the secretion of the alkaline bile and pancreatic juice, it causes
a reduction in the acidity of the other juices of the body and an increase
in their alkalinity. It produces, in other words, an alkaline tide
in the body Thus the urine is always reduced in its acidity during
the digestion of a meal and may even become alkaline. It is not
impossible that this alkaline tide may be part of the cause of the sen-
sation of well-being which accompanies the eating of a meal. A

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slight change of alkalinity of the cells very materially affects their

Variation of the character of the juice with the diet. — Among the
interesting facts found by Pawlow and his pupils by the use of the small
stomach was that the character of the juice varied with the character of
the diet. The juice was most powerfully proteolytic when the dog had
bread to eat and weakest when fed milk. The figures on page 380 illus-
trate the variation of the juice. It was also found that a sudden increase
in the rate of secretion not only increased the rate but also the concen-
tration of the juice, confirming a fact observed by Heidenhain. The
explanation of the difference in the activity of the juice on these different
diets has not been given. The juice which is secreted at the beginning
of an experiment is usually more active than that after the secretion has
gone on for a time, presumably owing to the fact that during secretion
some of the stored pepsinogen has been exhausted. Some of the varia-
tions noted may be due to the fact that not all the glands of the stomach
secrete at the same time. It is probable that the number entering into
activity may vary with the size of the meal ; some may be at rest while
others are secreting. If now by giving meat one arouses those which
have been resting, it is possible that their secretion would be more con-
centrated and more active than the secretion which has been derived
from the glands which had hitherto been in activity and which had been
partially exhausted.

How is the secretion of the juice produced and controlled?' Gas-
tric hormones. — There is no doubt that the secretion of the gastric juice
is under the control of nerves, the vagi and the splanchnics. The stimu-
lation of these nerves under proper conditions causes secretion of the
juice. Secretion is greatly reduced in the dog after section of the
nerves. If we ask the further question of how the nerves cause secre-
tion, we ask a question not yet answered. There seems to be evidence
that either owing to the stimulation of the mucosa by the nerves or other
, agencies, i.e., the food, there is produced in the stomach cells a substance
which when injected into the blood of another animal or intramuscularly
causes the secretion in that animal of gastric juice. Such a substance
as this is called a hormone, meaning " I rouse to activity " (Gr. hormon,
I rouse, or set in motion). As we shall see in other cases, there is some
reason for thinking that such substances are normally produced perhaps
in all cells under the influence of nerves and it is these substances which
directly stimulate the cell to activity. The work on the gastric hormones
is yet incomplete, but the observations of Edkins that such gastric hor-
mones exist have been confirmed in the author's laboratory (Keeton and
Koch). These hormone substances in the gastric gland are extracted
from the mucosa by hot acid and are hence probably substances of a

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basic nature. They are heat stable. The gastric hormone does not cause
secretion in the salivary glands, but only in the stomach. The question
of the relation of gastrin to secretin, the active secretory hormone of
the intestine, is still uncertain. They appear to have many properties
in common. Gastrin injected subcutaneously into dogs having Pawlow
pouches causes a copious secretion of typical gastric juice in the pouch
(Keeton and Koch). (See also Emsmann, Tomazewski and Ehrmann,
who have studied gastrin.)

Digestive actions of gastric juice. — 1. Action on proteins. It was
found by Spallanzani that gastric juice exerted a solvent action on
meats. Pieces of meat immersed in the juice gradually dissolve until
only a few fragments of fibers remain undigested. The cause qf this
solvent action was early studied. It was at first supposed that it was due
to the hydrochloric acid which had been discovered in the juice by Prout
in 1823, but experiment showed that pieces of meat immersed in solu-
tions of hydrochloric acid as strong as that of the gastric juice did not
dissolve at all, or at most they dissolved at a rate so slow as not to be
comparable to the action of the juice. There must be something else in
the juice to bring about this digestion. It was discovered by Schwann,
one of the founders of the cell theory, that if the juice was boiled first
it lost its digestive action, although its acidity remained. The active
principle, therefore, is destroyed by heat. Since the juice contains a
good deal of organic matter and this is coagulated by heat, it was sup-
posed that the active principle was organic in nature and Schwann pro-
posed that it be called pepsin (Greek, pepd&j^ digestion). Pepsin is,
hence, tne acititfc principle in the juice which digests meat, or, more gen-
erally, proteins, in an acid medium.

2. The clotting of milk. — Another property of the gastric juice
which was very early discovered is that it causes milk to coagulate, or
clot, so that it becomes jelly-like. Since acid by itself produces a simi-
lar physical change in «nilk, as is shown in the souring of milk, it
might be supposed that thisj3QjF£E_Qf-the gastric jukfiis due to the acid
^tjynt niT lfi ; fry tJfe j&i&jQQt the case. Carefully neutralized gastric juice,
particularly that of young animals, will still produce clotting if added
to neutral milk. The milk does not change its reaction in the process.
Even an aqueous extract, neutral in reaction, of the calf's stomach will
clot milk, although the action is faster in a faintly acid medium. If the
gastric juice or these extracts are boiled, they lose their power of coagu-
lation. Like pepsin, the active principle is found stored in the mucous
™ ATn |)r^fii Xfejg p AWpr of the juice is accordingly due to an active prin-
ciplej HLfi nzyme, and this enzyme is called rennet, or renniy,, or chymosin.
The mechanism of this clotting and the question of the identity or dif-
ference of pepsin and rennin will be discussed presently. Since this



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power of clotting milk is most pronounced in the stomachs of very young
animals, it is evidently in the nature of an adaptation to milk as an article
of diet, and the advantages possibly secured by it are discussed
farther on.

3. Action on carbohydrates. — Toward carbohydrates gastric juice
has a very unimportant action. Starch and dextrins it does not act
upon, b ut saccharose or cane sugar, which is the easiest of the disac-
charides to invert, is very slowly split in to le vnlftgfi and glu cose by the
hydrogen ions, or the acid of the stomach. There is, however, under
normal circumstances when no regurgitation has taken place from the
intestine, no enzyme in the gastric juice capable of digesting carbo-
hydrates. Lusk found that the inversion of cane sugar was no more
rapid than could be ascribed to the acid of the juice. Since lactose and
maltose are inverted or digested by acid much more slowly than cane
sugar, the action on these sugars is even less important than that on
cane sugar. All three are digested by enzymes found in the intestine.
To what extent cane sugar is inverted in the stomach will depend on
the length of time it remains there after free acid appears. This time
is normally so short that probably little inversion occurs. The concen-
tration of free hydrogen ions at the best is not more than .08 N, and in
a mixed meal is less than this. Such weak acid inverts slowly.

4. Action on fats. — Gastric juice has quite marked powers of
digesting fats which are already emulsified, such as the fats of milk
and of yolk of egg, but it has almost no power on non-emulsified fats such
as those in meat or butter. The power of the juice to digest emulsified
fats was described long ago by Ogata and confirmed by many observers,
but it was for some reason long omitted from the text-books. It has
recently been confirmed by the work of Volhard and his pupils. Thus
the fats of milk and yolk of eggs are split or digested into fatty acid
and glycerine to about 50-80 per cent, in the stomach, whereas non-
emulsified fat is split only to the extent of .5-iper cent, in the stomach.
The greater action on the fats of milk and yolk of eggs is probably due
to the fact that the area of contact between fat and water is much
greater owing to their emulsion. This power of the gastric juice to split
fats is still under investigation. There is no doubt that the action is
due to a fat-splitting enzyme in the gastric juice, or lipase as it is
called. For some time it was doubtful whether this lipase was secreted
by the stomach, or whether it had regurgitated into the stomach from
the intestine, the juices in the intestine containing much lipase, but
experiment has shown that lipase pre-exists in the stomach mucosa, and
also that the stomach lipase differs in the optimum acidity of its digestive
action from that of the intestine (Davidson).

5. Antiseptic action of the juice. — In practically all of the verte-

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brates the secretion in the stomach is strongly acid with hydrochloric
acid. The end secured in having an acid rather than an alkaline reac-
tion in this reservoir is presumably to check fermentation. Hydrochloric
acid kills all forms of living things' except spores. Many animals swallow
their food alive. Frogs eat each other, or snakes and other living ani-
mals. The tissues of these animals live well enough in an alkaline or
neutral digestive medium, but in the strong acid of the stomach they
are attacked, killed and digested. But probably of even greater impor-
tance is the additional protection secured against parasites of all kinds.
Animals are constantly eating with their food bacteria, moulds, protozoa
or other parasites which are killed by the gastric juice. Of the vast
numbers of bacteria we swallow the great majority are killed in the
stomach, and people having a copious and active gastric juice are less
liable to infection by typhoid and cholera than those with less acid juice.
The digested strongly acid material called chyme as it escapes from the
stomach is almost sterile and contains few living bacteria. Any reduc-
tion of the acidity is apt to be followed by a bacterial or yeast fermen-
tation in the stomach which may produce irritating organic acids and
gas. As long as hydrochloric acid remains in normal amount in the
stomach,. one never finds more than traces of lactic, butyric or other
acids which are produced by fermentation, but in the absence of hydro-
chloric acid these generally appear.

Action of the juice on proteins. — 1. Pepsin. Its origin. Pepsinogen.
We may now proceed to consider more in detail the nature and source
of the active principles of peptic digestion, namely the pepsin and the
hydrochloric acid, and the character and conditions of their action on

Pepsin is stored in the mucous membrane of the stomach. It was
found by Schwann that if the mucous membrane of the pig's or dog's
stomach, which is alkaline or neutral in reaction, is extracted with dilute
(0.4 per cent.) HC1 or extracted by water and then the water extract
mixed with acid to make about 0:3 per cent., the extract has digestive
powers similar to that of gastric juice.

This experiment showed that pepsin, or^a substance which gave rise
to it, wasstored^jn^ the muc osa of the stomach , but since the aqueous
extract of the membrane was neutral, it was clear that the hydrochloric
acid was not stored in the mucosa. The pepsin was probably made in
the mucosa between meals, but the hydrochloric acid must be made only
at the moment of secretion. Further facts about this pepsin were dis-
covered by Langley. He found that it was extremely sensitive to alka-
lies. If, for example, the juice be neutralized by sodium hydrate or
carbonate and then made acid again, it will be found to have lost much
of its activity. If it be made plainly alkaline, it is entirely inactive

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when reacidified, although the reacidification is made at once. The
p epsin has been destroyed or rendered inactive by the alkali. It is
necessary, if one wishes to neutralize the juice without destroying the
activity of most of the pepsin, to add CaCO a to it and then a very weak
alkali, such as sodium acetate or milk of lime, very cautiously. Langley
found that if an aqueous extract be made of the mucosa of the stomach,
this extract might be made slightly alkaline for a short time, but would
still be active if made acid again; but if an acid extract be made of
the stomach, this could not be made weakly alkaline without perma-
nently destroying its activity. It appeared, then, that the extract made
with water was more resistant to the action of alkali than the extract
";» thade with acid. Langley interpreted this to mean that the pepsin did
not exist as such in the muc ous membrane, but that there was an antece-
dent and more stable substancelrom which the active pepsin wa^IonSfid
by the action of acids. This more resistant antecedent substance_he
called _* [ pepsinogen/ 9 since it formed pepsin when acted on by acids.
Another evidence tiiat the substance in the mucous membrane differs
from pepsin is the fact that if carbonic anhydride gas be passed through
a neutral, aqueous extract of the frog's oesophagus, which contains pep-
sinogen, most of the pepsinogen is destroyed, but if the extract is first
acidified and then neutralized and carbonic anhydride passed through
it, it is not destroyed. PepsinogeiLis, then, more sensitive to carbon
dioxide and less sensitive to alkalies than pepsin. It has since been
shown that the loss of activity of the pepsin is~not permanent, as Lang-
ley thought, when the juice is carefully neutralized and then made alka-
line. The activity of the pepsin of such juice may be reobtained if acid
is very carefully added nearly to the neutral point and then after
standing twenty hours the reaction made acid. But there is no doubt
of the difference in resistance of pepsin to C0 2 and alkalies after and
before it has been treated with acid. If his explanation is correct, we
may then assume that pepsin exists in an inactive state in the mucosa as
pepsinogen and is set free by the acid. Since it is quite a common thing
for the enzymes to be in union in the cells with some colloidal matter,
the union being far more stable than the free enzyme, it is probable that
the explanation of Langley is the true one. The bald statement is often
made in the literature that pepsinogen and not pepsin exists in the
mucosa, but it is well to remember that this is as yet an inference and,
while quite probable, should not be stated as a fact.

The fact that pepsinogen is so very sensitive to carbonic acid gas,
whereas pepsin is not at all sensitive to it, is very interesting and may
throw light on the nature of the change which occurs when pepsinogen
is converted into pepsin. The reaction may be the carbamino reaction
of Siegfried (see page 121). If it is the carbamino reaction, then the

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change produced by acid in pepsinogen by which it is converted into
pepsin might be similar to the conversion of creatine to creatinine by
the action of acids. The pepsinogen might be represented thus:


CH 2 — COOH CH 2 — C =

Pepsinogen. Pepsin.

No importance is to be attached to the relative positions of the carboxyl
and amino groups in the above formula, but only that under the action
of the acid an anhydride may be formed like creatinine. The carbonic
acid in the presence of a calcium salt would combine as follows with the
pepsinogen, but not with the pepsin : x


<SH f CO—

Carbarn ino pepsinogen.

2. J Tyftqf cells jrfJlje miiAcmsmcmbrm^Jorm the pepswj The ques-
tion which followed immediately on the discovery of the fact that pepsin
or its antecedent, pepsinogen, existed in the mucous membrane in note-
worthy quantities was that of the location of this substance. A histo-
logical examination of the mucosa of the stomach showed it to contain
a large number of simple tubular glands. There are in these
glands in the fundus end of the stomach in mammals three kinds of cells :
namely, mucous cells near the neck of the gland, chief or adelomorphic
cells, and parietal or delomorphic cells. The latter are also called oxyntic
cells. Oxyntic means acid, and adelomorphic means " of uncertain
shape " (Gr. adelos, uncertain; morphe, shape). In the pyloric end of
the stomach the glands have no parietal cells and they differ in some
other particulars from those of the fundus end. The mucous cells secrete
mucin ; both the parietal and chief cells contain granules presumably of
a protein nature, but the granules are larger in the chief cells than in
the parietal, and these two kinds of cells differ in their affinities for
certain dyes. The granules are more abundant at certain times than at
others and it is believed, though it has not been demonstratively proved,
from analogy with other glands which can be observed in the living state,
that these granules, elaborated by the cell, are secreted or dissolved and
pass out from the cell when the latter secretes. They are probably pro-
tein in .nature, judging from their solubilities and relation to reagents,

"The reaction would probably occur in the absence of calcium, giving simply
the free carbamic acid compound. If ammonia is present a uramido compound might
be formed.

r__ CH— NH— COOH R— CH— NH— CO— NH 2

CH —COOH , or CH a — COOH.

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and it is natural to suppose that they constitute a portion at least of the
organic matter found in the gastric juice. Many have gone farther
than this and called them plainly zymogen granules and assumed that
they represent so much pepsinogen. They are in fact ordinarily called
ferment granules, but it must be remembered that this is an inference,
and whether the pepsin is represented by the granules or by some sub-
stances in solution in the protoplasm it is quite impossible to say at the
present time, although it is possible that some of the granules may con-
tain, or be, pepsin or pepsinogen itself. There is no question from the
work of Harvey and Bensley that the secretion of the parietal* cells
is alkaline and protein in character. These observers discovered an
intravital stain, cyanamine, which is blue when acid and red when
alkaline and which is taken up with avidity by the secretion in the
fine canaliculi of the parietal cells. The duct contents stain a clear
red by this stain and the blue is found only close to the neck of

Online LibraryAlbert P. MathewsPhysiological chemistry: a text-book and manual for students → online text (page 39 of 119)