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distillation method, and in its ingenious confirmation by analytical results, as described in
the text.

" Co7npt. rend. Acad. d. sc, Paris, 1844-.5 ; "Lemons de physiol. exper. applique a la
m(^d.," 1856, tome ii. p. 397.

'^ Jjer. d. Sachs. Gesellsch. d. Wissensch., Leipzig, 1847.

■^ Pelouse, Compt. rend. Acad. d. sc, Paris, tome xix. p. 1227 ; Thomson, L(md.
Edin. and JJitb. Phil. Mag., London, 1845.

8 "Traite analytique de la digestion," 1843; Jahresh. it. d. Fortschr. d. ges. Med.,
Erlangen, 1851, Bd. i. S. 97 ; 1858, Bd. 1. S. 37.

9 See p. 361.

1° "Die Verdauungssafte und der Stoffwechsel," Mitau u. Leipzig, 1852, S. 44.



THE ACID OF THE GASTRIC JUICE. 353

the result of eighteen concordant analyses, Schmidt found that gastric
juice always contained more hydrochloric acid than was sufficient to
neutralise all the bases present, and that the excess of hydrochloric acid
was alone sufficient to account for the entire acidity of the gastric juice.
Schmidt's course of procedure was as follows : —

The total chlorides in a weighed quantity (100 grms.) of gastric juice
were precipitated and weighed as silver chloride in the usual fashion, hy
adding a drop or two of nitric acid followed by slight excess of silver nitrate
solution. From the filtrate the excess of silver nitrate was removed by addi-
tion of pure hydrochloric acid, as silver chloride ; and the filtrate, containing
all the bases of the gastric juice, was evaporated to dryness, ignited, and the
amount of each separate base in the ash determined by appropriate methods.
In many cases the percentage of ammonia present was also determined in a
different portion as ammonio-platinic chloride.

The amount of hydrochloric acid present, combined and uncombined, was
found from the weight of the first silver chloride precipitate ; the weight of
chlorine necessary to combine with the weight of each base present was next
calculated, on the assumption that all of each base was actually present as
chloride ; and by adding all these weights of chlorine the amount of chlorine
(and hence hydrochloric acid) necessary to satisfy all the bases was determined.
This was found to be considerably less than the total chlorine present ; in fact,
the difference in the two amounts represented very accurately the total acidity
reckoned as hydrochloric acid.

The argument underlying Schmidt's experiments cannot be gainsaid,
and as the experimental part of his work was confirmed by other
observers,! there remained no choice but to accept the presence of
hydrochloric acid in the stomach as proven. This view accordingly
gained ground after the publication of his results, and is now universally
accepted.

Although Schmidt's experiments demonstrate that there is an excess
of hydrochloric acid in gastric juice, uncomhined ivith inorganic bases, they
do not show that this excess of acid is entirely uncombined. It is
certain that if the excess of acid is in chemical combination with any-
thing, the compound so formed is a very unstable one ; this is shown by
the ease with which the acid combines with fixed alkalies, and by the
persistence of the acid reaction in spite of the combination. Still there
are clear grounds for believing that the hydrochloric acid is in most
cases combined loosely with some other body, most probably albumose
or peptone, which are always present in traces in gastric juice. These
reasons are as follows : —

1. Organic acids do not dissolve calcium oxalate, but a solution of
hydrochloric acid in water, containing one part of acid in a thousand
parts of Avater, does dissolve this compound. ISTow gastric juice does not
dissolve calcium oxalate, from which Bernard and Barreswil ^ argued that the
acidity of gastric juice is not due to hydrochloric acid. This difference in
action on calcium oxalate of (a) a solution of hydrochloric acid in water, and
{h) gastric juice, is, however, probably due to the presence of albumoses and
peptones, which form a loose combination with the acid, of sufficient stability
to prevent it from acting on calcium oxalate.

^ Ch. Richet, "Le sue gastiique cliez I'liomme et les animaux," Paris, 1878, p. 32;
Maly, Ann. d. Chem., Leipzig, 1874, Bd. clxxiii. S. 227.

' CI. Bernard, "Lecons de pliysiol. exper.," 1856, tome ii. p. 395.
VOL. I. 2Z



354 CHEiMlSTR Y OF THE DIGESTIVE PROCESSES.

2. Laborde ^ compared the inverting power of gastric juice on cane-sugar
with that of a solution of pure hydrochloric acid in water, of equal acidity to
the gastric juice, and under similar conditions. He found that the hydro-
chloric acid inverted much more rapidly than the gastric juice, Avhich
possessed much the same inverting power as a solution of lactic acid of equal
concentration. He also found that gastric juice converted starch into grape-
sugar and dextrin much more slowly than a solution of hydrochloric acid
under similar conditions. On the other hand, Szabo - found that peptones do
indeed interfere with the action of dilute hydrochloric acid on starch ; but,
contrary to Laborde, found that the action of gastric juice on starch lies in
intensity much closer to that of hydrochloric than to that of lactic acid.

3. In treating of the digestive enzymes, it has been seen that these are
much less injured by hydrochloric acid, in presence of albumoses and peptones,
than by free hydrochloric acid alone, which shows that hydrochloric acid in
presence of albumoses and peptones behaves as if it entered into combina-
tion with them.

4. Berthelot and Jungfleisch ^ showed that, when a substance which is
soluble in each of two solvents, which are not completely soluble in each
other, is shaken up with a quantity of both solvents, it divides itself between
the two solvents so that the ratio of its concentrations in each is constant, and
does not vary with the proportion of the two solvents used, nor the amount of
soluble material used. This constant ratio they called the coefficient de
partage, which may be rendered in English "coefficient of distribution."*
For example, if succinic acid be well shaken up with water and ether, the
concentration of succinic acid in the watery layer will always be about six
times as great as in the ethereal layer, no matter, within wide limits,^ what
have been the quantities of ether, water, and succinic acid used ; the co-
efficient of distribution is here six. Mineral acids are much more soluble in
water compared with ether than are organic acids ; accordingly the co-
efficients of distribution of the mineral acids for these two solvents are
much larger than those of the organic acids.

Richet'^ made use of this property to test whether pure gastric juice con-
tains only hydrochloric acid, or hydrochloric acid plus organic acids. He
found that the coefficient of distribution was 137'1. To a portion of the
same gastric juice he next added barium lactate, and found that the co-
efficient Avas reduced to 9 "9, that of lactic acid is 8 "8 to 11 "0. This experiment
shows that the acid first present was a mineral acid, which afterwards dis-
placed nearly all the lactic acid from combination, so that in the second case
the acidity was mainly due to lactic acid. Eichet further added sodium
acetate (a) to a solution of hydrochloric acid in water ; (&) to gastric juice of
equal acidity, and found that in the first case the coefficient was reduced to
1'7 (practically that of acetic acid, 1"4), while in the second case the co-
efficient was only reduced to 5 to 5 "8. Kichet supposes that this difference is
due to the hydrochloric acid in the gastric juice being combined feebly with
some other substance. When sodium acetate is added to hydrochloric acid
alone, the base Avill be shared between the two acids in proportion to their
mutual avidities for it, which are in the ratio of 1 to '03. That is to say, about

1 Gaz. viM. dc Paris, 1874, Nos. 32-34, pp. 399, 411, 422.

- Ztsclir. f. pliysiol. Chtm., Strassburg, 1877, Bd. i. S. 140.

•* Anii. de chiin., Paris, 1872, Ser. 4, tome xxvi. p. 396. For a complete account of
this subject, see Ostvvald, " Lehrbuch der allgemeinen Chem.," Leij^zig, 1891, AuH. 2,
Bd. i. S. 809.

'' This term has been proposed by Gamgee, "Physiological Chemistry,'' vob ii. p. 97,
as well as "coefficient of repartition."

^ The quantities of solvent must be so chosen, compared with the quantity of soluble
substance, that the sohitions are not too concentrated.

^ "Le sue gastrique cliez I'honime et Ics anijnaux, ses proprietes chemiques et physio-
logiques," Paris, 1878, p. 37.



THE ACID OF THE GASTRIC JUICE. 355

97 per cent, of the base will be combined witli the hydrochloric acid, and
3 per cent, with the acetic acid ; or, otherwise, 3 per cent, of the hydrochloric
acid will be free and 97 per cent, of the acetic acid, supposing that equivalent
quantities of the two acids are present.^ Such a mixture would possess only
a slightly higher coefficient of distribution than acetic acid, Eut if the
sodium acetate be added to hydrochloric acid, already feebly combined with
something else, the power of the acid to combine with the sodium will be
diminished, on account of the tendency to remain combined with this sub-
stance, and the amount of hydrochloric acid uncombined with sodium will be
increased ; this will remain to a greater extent in the watery layer, and on
shaking with ether the coefficient of distrihutio7i will be much greater than
that of acetic acid.

Ricliet found traces of leucine in the gastric mucous membrane, and be-
lieves, mainly on this ground, that the hydrochloric acid of the gastric juice
is in combination with leucine. But there is no good reason for going so far
afield to seek a partner for the hydrochloric acid; any substance in combination
with the acid would produce such an effect as Richet obtained, and it is far
more probable that the hydrochloric acid is in combination with the albumoses
of the gastric juice than with leucine, especially as leucine has not been found
in gastric juice, and hydrochlorate of leucine does not act as an acid to pepsin,
as shown by the inability of a mixture of the two to digest proteids.^

This account of Richet's work has been placed here on account of the bear-
ing of the latter part of it on the question of the combination of the hydro-
chloric acid, but the first part of it is also of great value in showing that pure
gastric juice is practically free from organic acid.

Organic acids present during carholiydjrate digestion. — Although organic
acids are entirely absent in pure gastric juice, or at most are only present
in traces, this is by no means the case during digestion, especially of food
rich in carbohydrates.

The food passing into the stomach during a meal is alkaline in
reaction, by reason of the saliva with which it is abundantly mixed ; and
in addition, during and after a meal a considerable quantity of saliva is
swallowed by itself. As Beaumont ^ and others have shown, there is no
secretion of acid gastric juice when the stomach is empty, and although
active secretion begins with the arrival of the first portions of food in
the stomach, some time must elapse before the alkaline reaction of the
masses of food and saliva is neutralised by the acid of the gastric juice,
and a reaction due to free hydrochloric acid established, after saturation
of the soluble proteid of the food. This interval is exceedingly difficult
to estimate, the delicate colour reactions for free hydrochloric acid being so
deceptive in a heterogeneous fluid like the contents of a stomach ;
van de Velden * states that it varies from half an hour to two hours,
and is on an average three-quarters of an hour. During this time con-
version of starch by ptyalin goes on,^ and in addition bacterial action
begins with the production, from the carbohydrate part of the food, of
lactic acid,® accompanied by traces of butyric and acetic acids.

^ J. Thomsen, " Thermocliemische Untersucliungen," Ami. d. Phys. u. Oliem., Leipzig,
1869-1871, Bde. cxxxviii.-cxliii.

^ See Gamgee, "Physiological Chemistry," voL ii. pp. 97-99.

' See article on "Mechanism of Gastric Secretion."

'^ Ztschr.f. pliysiol. Chem., Strassburg, 1878, Bd. ii. S. 205.

° See under " Ptyalin," p. 329.

•^ According to Maly, the greater part of the lactic acid is the ordinary lactic acid of
fermentation, but this is accompanied by a smaller quantity of sarcolactic acid, which may
occasionally be much increased in amount, £er. d. deutsch. chem. Gcsellsch., IBerlin, 1874,
S. 156 ; Ann. d. Chem., Leipzig, 1874, Bd. clxxiii. S. 227.



356 CHEMISTR Y OF THE DIGESTIVE PROCESSES.

It was long believed that this action was due to the growth of the
Bacillus acicli lactici on sugar only, either that of the food or that produced
by the action of ptyahn on the starch of the food. Brllcke ^ has shown,
however, that starch can he also changed into lactic acid without con-
version by ptyalin, by demonstrating that soluble starch, erythrodextrin
and lactic acid, are found in the stomach of the dog after a meal contain-
ing boiled starch. oSTow the saliva of the dog contains no ptyalin, so that
these products must be formed directly from starch. Traces of sugar
are also foimd, and Briicke supposes that sugar is first formed by the
action of the haderium but immediately becomes converted into lactic acid
by its further action. A similar change in starch paste takes place on
standing in the air.

Goldschmidt ^ divides gastric digestion in the horse into four stages,
which are, however, not sharply marked off, but merge into one another.
(1) No proteolysis, acid reaction due to lactic acid. (2) Proteolysis
and amylolysis proceed together, both lactic and hydrochloric acids
present. (3) Stoppage of amylolysis in the middle part of the stomach,
in this portion only hydrochloric acid, elsewhere lactic acid. (4) Stop-
page of amylolysis everywhere ; hydrochloric acid only present in all
parts of the stomach. Ewald and Boas^ describe a similar state of
affairs in the healthy human stomach under normal conditions after
a carbohydrate meal. In the first stage (from ten to thirty minutes after
the meal) lactic acid alone is present ; in the second, lactic and hydro-
chloric acids are present together, but the former rapidly disappears so
soon as any free hydrochloric acid is present ; and in the third stage,
hydrochloric acid alone is present. This disappearance of the lactic acid
is very interesting, as showing that it is rapidly absorbed in the
stomach.

Other inorganic acids free in imrc gastric juice hcsicles hydrochloric
acid. — It must not be assumed, from the usual mode of stating the
results of quantitative analysis of gastric juice,^ that hydrochloric acid is
the only inorganic acid present in the gastric juice. AH the phosphoric
acid is not united, in the gastric juice, to calcium, magnesium, and iron
to complete saturation, as usually set forth in such analytical results ;
nor are all the bases saturated by the hydrochloric acid, and only that
amount of hydrochloric acid free, which is left over after so saturating
them.^ Suppose a solution in water of neutral chlorides is taken, say
such a solution as the gastric juice would be, minus its free hydrochloric
acid and its j)hosphates, and to this phosphoric acid is added. As soon

1 Briicke, Sitzung.^h. d. k. Akad. d. JFissensch., Wien, 1872, Bd. Ixv. Abtli. 3, S. 126 ;
" Vorlesungen," Wicn, 1885, Aufl. 4, Bd. i. S. 321. See also W. de Bary, Aoxh. f. exper.
Path. u. Pilar malcol., Leipzig, 1886, Bd. xx. S. 243.

- Zischr. f.pliysiol. Chem., Strassburg, 1886, Bd. x. S. 361. See also Ellenberger and
Hofmeister, Jahresb. u. d.-Fortschr. d. Thier-Chcm., Wiesbaden, 1885, Bd. xv. S. 284, 301 ;
1886, Bd. xvi. S. 260, 261.

3 Virchow's Archiv, 1885, Bd. ci. S. 325 ; 1886, Bd. civ. S. 271 ; Ewald, " Kliuik der
Verdanungskrankheiten," 1890, Bd. i. S. 83.

•* See i>. 350.

^ This was merely an assumption made Ijy Schmidt, in order to conclusively show that
gastric juice contained an excess of hydrochloric acid al)ove even iJiis quantity. Fortunately,
the excess of hj^lrochloric acid was sufficient to allow Schmidt to give this form of proof;
but if the quantity of j)hosphates had been greater, or the excess of hydrochloric acid less,
Schmidt's process might easily have yielded a negative result, and yet the gastric juice
have contained free hydrochloric acid ; indeed, the massed equivalent in chlorine of the total
bases might have been greater than the total quantity of chlorine present, and still there
might have been free hj'drochloric acid present.



THE ACID OF THE GASTRIC JUICE. 357

as the phosphoric acid passes into solution, it no longer remains present
as free phosphoric acid, to the amount to which it has been added, but
reacts with the other salts present in solution, displacing a definite
amount of each metal from combination with chlorine, thus setting free
hydrochloric acid and forming phosphates, so that there comes to 1je in
solution free hydrochloric acid and free phosphoric acid, comljined
phosphoric acid, and combined hydrochloric acid (that is, chlorides and
phosphates). When a polybasic acid, such as phosphoric acid, is present
in solution, the matter is somewhat further complicated by there being
certain steps between free acid and combined acid, namely, acid salts ;
these also are represented in the distribution of bases among the acids,
so that there are in solution free acids, acid salts, and neutral salts. In
pure gastric juice, then, the acidity is in chief due to hydrochloric acid,
but also in part to acid phosphates and phosphoric acid, and the amount
of each of these free is perfectly determinate, and depends upon the
amount of each base and each acid present. For one fixed distribution
only can there be chemical equilibrium in the solution ; the introduction
of any salt, acid, or base into the solution will alter this equilibrium, and
a new distribution to suit the new conditions will occur, giving rise
again to equilibrium.

The facts stated above follow directly from Thomsen's^ "avidity
law." Thomsen arrived at this law by comparing the amount of heat
set free when an equivalent weight of a base unites with a mixture of
equivalent weights of two different acids, with the amount set free when
it combines with each acid separately.^ The law is that no acid in solu-
tion is combined with the bases present, to the complete exclusion of
other acids, however weak (as it is popularly expressed), which may be
simultaneously present in the solution ; but the acids share the bases,
according to their different avidities. Thomsen w^orked out a number of
avidity coefficients. Those of the organic acids are much smaller than
those of the inorganic acids. Thus, taking the avidity coefficient of
hydrochloric acid as unity, that of oxalic acid is '25, tartaric acid '05,
acetic acid 'OS. These coefficients mean, for example, that if one
equivalent each of sodic hydrate, of hydrochloric acid, and of oxalic acid,
be mixed in solution together, four-fifths of the base is combined with
the hydrochloric acid and one-fifth with the oxalic acid, and con-
sequently one-fifth of the hydrochloric acid is free and four-fifths of the
oxalic acid.

Maly ^ has also shown qualitatively, by a method of diffusion, that
this displacement of a strong acid {i.e. acid with a large avidity co-
efficient) by a weak acid (acid with a small acidity coefficient) takes

^ " Thermochemische Untersuclmngen," Ann. d. Phys. u. Chem., Leipzig, 1869-71,
Bde. cxxxviii.-cxliii.

^ Let « be the amount of heat in heat units developed when, say, one equivalent of
NaOH in grammes combines with one equivalent of HCl, and b that when it combines
with an equivalent of HNO3, c that when it partially combines with a mixture of one
equivalent of HCl and one equivalent of HNO3, also let x be the fraction which combines
with HCl. Then, since a is the amount of beat set free when a whole equivalent of
NaOH unites with HCl, a x will be that set free when the fraction x combines ; similarly
b {1-x) will be the amount set free by the combination of the fraction (1 -x) with HNO3;
the sum of these two must equal c, the amount of heat actually observed ; therefore a x +
b (1 -x) = c, from which x and 1-x can be determined. Their ratio is the measure of the
avidity of the two acids for combining with the base.

^ Ann. d. Gliem., Leipzig, 1874, Bd. clxxiii. S. 250; Sitzungsb. d. Ic. Al:ad. d.
TVissensch., Wien, 1874, Bd. Ixix. Abth. 3, S. 251 ; Ztschr. f. j^liynol. Chem., Strassburg,
1877, Bd. i. S. 174.



358 CHEMISTR Y OF THE DIGESTIVE PROCESSES.

place in solution. He dissolved sodium chloride and lactic acid together
in water, placed the solution in the bottom of a cyhndrical vessel, and
then carefully poured a layer of distilled water on the top. After some
days, part of the upper layer was removed and analysed ; it was found to
contain more than sufficient chlorine to balance all the sodium present ;
that is to say, it contained free hydrochloric acid. Similar results were
obtained with a mixture of monosodium phosphate, and other acid salts,
in common solution with sodium chloride.

These results of Thomson and Maly will be again referred to in
discussing the mode of origin of hydrochloric acid. They are introduced
here to show that any weaker acids in gastric juice along with the
hydrochloric acid must in part be uncombined. Any organic acids
present during digestion will also be in part free and in part combined,
and as these have very small avidities compared with hydrochloric acid,
they will be almost completely free. This has a bearing of some import-
ance. Any organic acids formed in the stomach by bacterial action on
carbohydrates will be found as free acids, and will not reduce the amount
of free hydrochloric acid,^ but salts of organic acids entering the stomach
with the food will reduce the amount of acidity due to free hydrochloric,
because, from the organic salts, free acids will be formed, by hydrochloric
acid combining with their bases.

Source of tlie hydrochloric acid. — The only possible source of chlorine
lies in the chlorides of the food, and from this either directly, or indirectly
through the blood, the hydrochloric acid must necessarily have its origin.
That the chlorides present in the blood plasma are the source of the acid,
has been experimentally proved by Voit ^ and Cahn.^

Following a method first used by Yoit, Cahn fed dogs exclusively
on meat which had previously had all its salts extracted by boiling it
repeatedly with distilled water. An animal fed in this manner continues
to excrete a diminishing quantity of chlorides in the urine for a period
varying from two to five days. After this only traces of chlorides are
found in the urine, but the tissues and blood still cling on to their
necessary minimum quantity of chlorides, digestion goes on, and the
animal lives. At this period, if the contents of the stomach are washed
out with distilled water, the secretion is found to contain free acid and
to possess digestive power. If now the ammal's reserve stock of chlorine
be still further reduced by administering diuretics, such as potassium
nitrate, which cause some additional chlorides to be excreted ; or if free
hydrochloric acid be repeatedly removed by pumpmg out the contents of
the stomach with the aid of distilled water, a condition is finally reached
in which the stomach se.cretes a completely neutral fluid, which is
altogether inactive so long as it is neutral, but quickly digests fibrin if
1 part per 1000 of hydrochloric acid be added to it. When this
stage is reached the animal rapidly fails ; but if a small quantity of
sodium chloride be now given to it, it rapidly recovers, and soon becomes
in every respect normal.

This experiment also shows that the secretion of pepsin is independ-
ent of that of acid, and that in the absence of hydrochloric acid no

1 In fact will slightly increase it Ijy combining to a certain extent with the bases of the
chlorides.

^ Sitzimgsb. d. Jc.-bayer. Akacl. d. Wissensch. zu Milnchcn, 1869, Bd. ii. S. 483. See
also M. Gruber, Beitr. z. Physiol. C. Ludwig z. s. Gehurtst., Leipzig, 1887.

'^ Zlschr. f. physiol. Chem., Strassbnrg, 1886, Bd. x. S. 522.



THE ACID OF THE GASTRIC JUICE. 359

lactic acid or other organic acid is formed, which disproves the theory
that lactic acid is first formed and then decomposes sodium chloride, so
forming free hydrochloric aeid.^

It may here be pointed out that experiments have been made by
Nencki and Schoumova-Simanowsky ^ to ascertain the possibility of
replacing the chlorine by other halogens, so as to form hydrobromic or



Online LibraryE. A. (Edward Albert) Sharpey-SchäferText-book of physiology; (Volume v.1) → online text (page 50 of 147)