E. A. (Edward Albert) Sharpey-Schäfer.

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hydriodic acids. These experiments were performed on dogs operated
on by Pawlow's method,^ and the animals were fed with food in which
sodium chloride was as far as possible absent. Some had added to their
food sodium bromide, others sodium iodide. The administration of
sodium bromide resulted in the animals becoming so ill after a week or
so that the experiments had to cease. The gastric juice was secreted as
before, but the hydrochloric acid was largely replaced by hydrobromic
acid. In the case of those dogs to which sodium iodide was administered,
though less general disturbance resulted from the administration than
was the case with sodium bromide, yet the amount of hydriodic acid
replacing hydrochloric acid was very small.

Becvprocity hehveen the secretion of liyclrochloric acid and the reaction
of the urine. — That the hydrochloric acid of the gastric juice is formed
from the chlorides of the blood plasma, is likewise shown by Maly's *
observation that at the same period after a meal at which the secretion
of gastric juice is at a maximum, the acidity of the urine is at a minimum,
and may be replaced by an alkaline reaction. One function of the kidneys
is to preserve unaltered in degree the alkalinity of the blood. If now
neutral salts, such as sodium chloride, be removed from the blood, split
up in some manner by the agency of the gastric gland cell into hydro-
chloric acid and sodic hydrate, of which the hydrochloric acid is sent
towards the stomach cavity, while the alkali is expedited in the opposite
direction back to the blood stream, it follows that the alkalinity of the
blood will be increased. Hence, to preserve equilibrium, the kidneys
must excrete a less proportion of acid salts, or, if the rate of increasing
alkalinity of the blood demands it, must separate an alkaline fluid from
the blood. This is experimentally found to be the case. Under ordinary
circumstances, the kidneys preserve the constant value of the alkalinity
of the blood, by excreting phosphates of the alkalies so proportioned that
the reaction is acid, but during active digestion, 2 to 4 hours after a full
meal such as dinner, the relative amounts of bases and phosphoric acid
are so altered that the reaction becomes neutral or faintly alkaline, or, as
it is often commonly but not very exactly expressed, in the first case
monosodic phosphate (NaH.,PO^) is secreted with acid reaction ; in the
second, disodic phosphate jSra2HP04 with alkaline reaction.^

Theories as to the mode of origin of the hydrochloric acid. — Many
ingenious theories have been proposed to account for the specific function
of the gland cells of the stomach, of splitting up such a stable substance

1 See p. 352.

" Arch. f. exper. Path. u. Pharmakol., Leipzig, 1894, Bd. xxxiv. S. 313.

^ See article on "Meclianism of Gastric Secretion."

'^ Aom. d. Chem., Leipzig, 1874, Bd. clxxiii. S. 232. See also Quincke, Jahrcsh. u. d.
Fortschr. d. Thier-Chem., Wiesbaden, 1874, Bd. iv. S. 241 ; Stein, ibid., 1876, Bd. vi.
S. 161.

^ The reaction will really vary according to the relative amounts of base and acid
present. Monosodic phosphate alone dissolved in water has an acid reaction, disodic
phosphate similarly has an alkaline reaction, and mixtures in varying proportions can
have acid, neutral, or alkaline reaction. Li a complex mixture such as urine, no one can
say to what the reaction is due, but only that there is an excess of alkali or acid.


as sodium chloride, of forming such a strong acid as hydrochloric acid is
in the face of the alkalinitj of the blood, and of determining an alkahne
stream towards the blood and an acid stream towards the lumen of the

The oldest theory was, that the process was an electrolytic one.
Blondlot^ supposed that by electric agency sodium chloride in the
stomach wall was broken up into sodic hydrate and hydrochloric acid
(in the language of to-day, hydrolysed, lSraCl + H20=NaH0 + HCl).
The free acid then, for the most part, acted on the calcium phosphate
of the blood, forming acid phosphate and a trace of phosphoric acid,
while a trace of hydrochloric acid also remained free. To such a mixture
of acid substances (mainly acid calcium phosphate) he ascribed the
acidity of gastric juice. He electrolysed tricalcic phosphate, suspended
in a solution of sodium chloride, and claimed to have obtained such
products as his theory demands. Briicke ^ considered that the energy
required came from transformation of nervous energy, modified to this
purpose, and, admitting that the details are not explicable, compared the
effect to others called forth by nerve impulses, such as the electric effects
in the electric end-organ of some fishes. He also considered the secretion
of acid more analogous to electrolysis than to any other known process.
Lussana ^ supposed that in the glands of the stomach a decomposition of
the salts of the plasma took place, and that the preponderating part of
the free acid of the gastric juice was hydrochloric, simply because by far
the greater part of the salts of the plasma are chlorides. He tried to
test his theory by intravenous injection of salts not present in quantity
in blood plasma, such as sulphates and phosphates. He did not,
however, obtain the corresponding acids in the gastric juice, except
in the case of borax and tartar emetic, after injection of which traces
of boric and tartaric acids respectively were found in the gastric juice.

Buchheim* suggested that the chlorides of the plasma combined
with the proteid, so that the metal combined with one proteid molecule
and the acid radicle with another ; the latter combination being absorbed
by the acid-secreting cells and broken up there into proteid and acid.

These older theories can at best be only regarded as mere specu-
lations ; there is absolutely no experimental proof of them. Nor can
we lay claim at the present day to a complete knowledge of the
process of secretion of hydrochloric acid. Only thus far the progress
of physical chemistry, and a more exact knowledge of the laws of
solutions, has brought us, that we no longer need look upon the
production of hydrochloric acid by the animal organism as a chemical
wonder. The secretion of hydrochloric acid is still a mystery as great
as the secretion of pepsin or any other product of cell activity, but
no greater.

To the chemist, before the thermochemical work of Thomsen, and
the diffusion experiments of Maly already described,^ and when he was
acquainted with no other means of setting free hydrochloric acid from
its salts than the electric current or displacement by a stronger acid
such as sulphuric acid, the occurrence of hydrochloric acid in the gastric

1 " Traite analytique de la digestion," Nancy et Paris, 1843 ; Jaliresh. ii. d. Fortschr.
d. ges. Med., Erlangen, 1851, Bd. i. S. 97; 1858, Bd. i. S. 37. See also Ralfe, Lancet,
London, 1874, vol. ii. p. 29.

2 "Vorlesungen," Wien, 1885, Aiifl. A, Tli. 1, S. 307.

^ Jahrcsb. ii. d. Fortschr. d. ges. Med., Erlangen, 18G2, Bd. i. S. 110.

^ Arch.f. d. ges. Physiol., Bonn, 1876, Bd. xii. S. 332. « ggg p_ 357.


juice was an unsolvajjle riddle. But when Thonisen had sliown that
the weakest acid is in some measure capaljle of displacing the strongest
from its salts, and Maly that by a simple process of diffusion this strong
acid may be afterwards separated, the subject assumed a difi'erent aspect.
It was no longer necessary for the cell to be endowed with some force
of sufficient intensity, to directly break up such stable substances as the
alkaline chlorides. All that was necessary was that the cell should be
able from the organic material at its disposal to form an organic acid,
and afterwards to rapidly excrete the small fraction of hydrochloric
acid formed by the interaction between this organic acid and the neutral
chlorides, so that a fresh quantity of hydrochloric acid may be formed
by the mass action of the remainder of the organic acid on the remainder
of the chlorides. The organic salts so formed can then decompose by
cell activity into organic acid and base again, and the base be returned to
the blood stream. Since gastric juice is not accompanied by an organic
acid, this must be retained in the cell and induce a continuous cyclic
change. It is thus possible, with the aid of the new facts of physical
chemistry, to see that the process of secretion of hydrochloric acid can
be reduced to the same level as that of the secretion of any organic

This, however, is but a small portion of the entire problem. As Bunge
says : " In the appearance of the free hydrochloric acid Ues nothing puzzling.
Puzzling only is the power of the epithelial cell to send the hydrochloric acid
freed from the sodium chloride streaming always in one direction towards the
lumen of the gland, and the sodium carbonate ^ simultaneously formed always
back in the opposite direction towards the lymph and blood channels. But
such a puzzle we meet everywhere in the living tissue. Every cell possesses
the power to dispose of material in a suitable manner, attracting or repelling
it and sending it streaming in different directions." -

Maly 8 theory. — Maly has attempted to build on a purely physical
basis a theory of the formation of hydrochloric acid from the chlorides of
tlie blood, of which the following are the outlines : ^ —

1. There are no theoretically alkaline salts in the blood. Blood
plasma owes its alkalinity to two theoretically acid salts, di-sodic
phosphate (Na2lIP04), and sodium bicarbonate (]SI'aIIC03) ; besides
these two acid salts plasma contains excess of carbonic acid.

2. Disodic phosphate in presence of calcium chloride forms some
free hydrochloric acid, thus: — 3CaCl2+2]Sra2HP04=Ca3(P04)2+4NaCl+

Chiefly from the facts above stated, Maly supposes that by the
interaction of these theoretically acid salts of the plasma, on the chlorides
present with them in solution, traces of hydrochloric acid are formed ;
these traces of hydrochloric acid are rapidly removed, on account of the
high diff'usibility of hydrochloric acid,^ by the gland-cells which act as a

^ Bunge is considering the hydrochloric acid as set free by the action of carbonic acid.

-Somewhat freely translated from Bunge, " Lehrbuch der physiol. Chemie," Leipzig,
1894, Aufl. 3, S. 148.

3 Abstracted from Maly, Hermann's "Handbuch," Bd. v. (2), S. 66.

■* R. Pribram, Jahresb. il. d. Fortschr. d. Thier-Chem., Wiesbaden, 1871, Bd. i. S. 107 ;
Gerlach, ibid., 1873, Bd. iii. S. 109.

^ Graham has shown that the free acids diffuse more rapidly than their salts ; HCl
diffusing thirty-four times as rapidly as NaCl. Graham was also the first to show that, by
diffusion of acid potassium sulphate, sulphuric acid Avas obtained in tlie dialysate, while
normal sulphate remained behind.


perfect diffusion ^ apparatus ; on the removal of the hydrochloric acid,
fresh acid is formed by further mass action on the chlorides. The
kidneys or sweat glands probably do not so secrete hydrochloric acid,
because they are not such perfect diffusion arrangements as the gastric
glands, and cannot bring about such a molecular separation as the latter.

Ohjedions to Malys theory. — 1. Modern work has shown that the
alkahne reaction of theoretically acid salts is probably due to a hydro-
lysis taking place on solution. Thus on dissolving sodium bicarbonate
there are formed sodic hydrate and carbonic acid (NaHCOg + H20=:NaOH
+ H2CO3) ; and the sodic hydrate being a powerful base, and the car-
bonic acid a weak acid, one equivalent of the base more than balances
two of the acid, and the reaction is alkaline. On the other hand, when
acid potassium sulphate is dissolved, there is one equivalent in solution
of a strong base, and two equivalents of a strong acid, and the reaction
is acid. Such an hydrolysis of phosphates of the alkalies also takes
place. Trisodic phosphate yields an equivalent of base to one of acid,
and the reaction is intensely alkaline ; disodic phosphate yields only two
equivalents of base to three of acid, but the reaction is still alkaline ;
while monosodic phosphate yields but one equivalent of base to three of
acid, and at last the reaction is acid. A mixture of mono- and disodic
phosphates in proper proj)ortion would be neutral. In fact, after these
salts are dissolved, they no longer exist as such, but there are present in
solution bases and acids in certain concentrations, and the reaction of the
solution will depend on which of these acts most strongly on the in-
dicator. Now the hydrolysing effect on the neutral salts, chlorides, etc.
(if such are also present in solution), of these so-called acid salts must
closely resemble their effect on the indicator.

Whether there will be a tendency to formation of hydrochloric acid
or not from sodium chloride, will be determined by whether the attraction
of the acids (phosphoric and carbonic) for the base is greater or less
than the attraction of the bases for the hydrochloric acid. The reaction
of the solution of phosphates and carbonates in the plasma is alkaline,
which shows that the latter is the case, and that, therefore, there will be
no hydrochloric acid formed.

2. The continuous formation of hydrochloric acid by a reaction
between disodic phosphate and calcium chloride is impossible, because it
necessitates the formation of insoluble tricalcic phosphate, and as the
supply of calcium chloride is small, must soon stop.

3. Even if it be admitted that there are traces of hydrochloric acid
in the blood, there is no reason, if the process be purely one of diffusion,
why it should not go on continuously. This it does not do, but ceases
when digestion is not going on, and when digestion begins is secreted in
such amount that no mere physical diffusion could bring it through the
epithelial cells fast enough ; not to speak of separating it from a fluid
in which it is supposed to be present in traces only.^

^ By a perfect diffusion apparatus {voUkommener Diffttsions-ajpparat) Maly seems to
mean here semipermeable membrane ; that is, an arrangement permeable to the hydrochloric
acid and not to the other dissolved substances.

^ Gastric juice contains at least 2 parts per 1000 of hydrochloric acid ; the amount of
hydrochloric acid formed by mass action in a solution of 6 parts per 1000 of sodium
chloride, and a stillsmaller quantity of monosodiiim phosphates, no one has ever attempted
to measure, but it must be many thousand times less than this ; so that not only must the
hydrochloric acid ditfuse with a tremendous velocity, but it nuist get infinitely more con-
centrated in the process of diffusion, which, under j^urely physical conditions, so far as
we know them, is an utter impossibility.


These facts indicate that the formation of hydrochloric acid is a
process going on in the cell, that the acid is a cell secretion, and not a
diffusate from the blood plasma.

Ganigees modification of Malys theory. — Gamgee,^ while retaining
the supposition that the hydrochloric acid is formed by the action of
the alkaline phosphates on the chlorides, removes the seat of action from
the blood to the parietal cells. He supposes that these cells possess a
peculiar selective absorption for the phosphates of sodium, both alkaline
and acid, and for chlorides, and that within the cell there occur the
same reactions between these substances as occur in vitro when they
coexist in solution. One of the products of the reaction will then be
hydrochloric acid, which, in virtue of its high power of diffusion, will
pass, as soon as formed, into the secretion of the gland. This supposition
is certainly a step in the right direction, in so far as it brings the seat
of action to the cell— a much more probable place than the blood — but,
on the other hand, it assumes a good deal, without overcoming many of
the objections to Maly's theory. Thus, selective absorption, of both
alkaline and acid phosphates (probably di- and mono-sodium phosphates)
is assumed. Unless these are also assumed to be absorbed in such pro-
portions that the reaction of the cell contents becomes acid, no formation
of hydrochloric acid will take place, for, under merely physical conditions,
no such formation can be demonstrated in vitro.

Unless, again, the substances selectively absorbed are kept out of
action in some equally obscure manner by cell activity, there is no
reason why the secretion of acid should not be continuous ; and if absorp-
tion of phosphates and chlorides only begins at the commencement of
digestion, it is not easy to see how the traces of hydrochloric acid,
formed by such interactions, can keep pace with the demand then made
for hydrochloric acid.

Lastly, there is no experimental evidence that there is any such
selective absorption of phosphates and chlorides by the parietal cells.
And if a purely physical theory is to be abandoned, and a specific functional
activity of the cell invoked, there remains no reason for adhering to
theories which have been evolved on a purely physical basis.

It is easier, and more in accordance with our notions regarding the
secretion of other substances, to suppose that the hydrochloric acid
is formed by cell activity in some metabolic process, from the chlorides
and organic matters at its disposal. There are an infinite variety of
such processes capable of taking place, under the varying conditions of
cell life. It is true we do not know the details of these, nor why such
processes take place under certain given conditions ; nevertheless we
see the end-results, and there is no reason why hydrochloric acid should
not also be the end-product of such a cell metabolism rather than the
product of a kind of specialised diffusion.^

^ " Physiological Cliemistiy, " 1893, vol. ii. p. 113.

" Hammarsten, " Lehrbuch der physiol. Chem.," Wiesbaden, 1895, Aufl. 3, S. 242.
See also Heideiihaiii, Hermann's Handbnch,"Bd. v. (1), S. 151. One such possible process
is the formation in the cell of an organic acid which does not diffuse away, but is retained
in the cell and exercises a continuous action on the chlorides, forming hydrochloric acid
which the cell actively excretes. Another possibility would be the formation during
rest of an organic chlorine-containing substance, while the base combined with carbonic
acid passed into the blood, and the subsequent breaking up during activity of this
chlorine-compound yielding hydrochloric acid. There are indeed many courses which such
a cell-metabolism might take yielding hydrochloric acid as an end-result. See also Bunge,
" Lehrbuch der physiol. Chemie," Leipzig, 1894, Aufl. 3, S. 149.


Function of the liyclrochlorie acid. — One obvious purpose of the
hydrochloric acid of the gastric juice is to confer activity on the pepsin
accompanying it, which is only active in an acid medium. But, as
Bunge ^ pomts out, the estabhshment of an acid reaction is not necessary
for proteid digestion. In the pancreatic juice another proteolytic
ferment, trypsin, is found, which acts most powerfully on proteids in an
alkaline medium. A much more important function of the hydrochloric
acid lies, according to Bunge, in its powerful action as a disinfectant
and germicide, in destroying bacteria introduced with the food. In this
manner the formation of decomposition products, and the disturbance
tliereby produced in the normal course of digestion, is prevented, and
also in many cases the animal is preserved from the attacks of patho-
genic bacteria by the destruction of these or their spores.

Modern research has, in fact, led to the remarkable result, that the
average amount of hydrochloric acid found in the gastric juice just about
coincides with that which is found experimentally to be required to stop
the growth of most fermentative organisms and many pathogenic

Spallanzani ^ first called attention to the powerful preservative action
of gastric juice, and not only showed that gastric juice prevented
putrefaction, but that it stopped putrefaction which had already com-
menced. This he showed by feeding dogs on pieces of flesh which had
commenced to putrefy. After a short interval of gastric digestion the
flesh lost all putrefactive odour.

The action of the gastric juice on the bacilli of tubercle and splenic fever
has been investigated by Falk,* and by Frank. ^ Falk found that the bacillus
of splenic fever [B. anihracis) is easily destroyed by gastric juice, but that
its spores escape destruction, and that the tubercle bacillus is unaffected by
gastric juice. Frank completely confirms these results, and both observers
are agreed that the gastric juice is incapable of making any very effectual
resistance to infection of the organism by these pathogenic bacteria. The
comma bacillus of cholera, however, is readily destroyed by gastric juice or
dilute hydrochloric acid.*^ Cholera cannot be communicated by the mouth in
healthy animals ; but, after washing out the stomach with alkaline solutions,
symptoms resembling those of cholera follow introduction of a pure culture of
the cholera bacillus, as is also the case when this is introduced into the

The acetic and lactic fermentations are stopped by mere traces of free
hydrochloric acid, while acid combined with proteid is ineffectual. According
to Cohn, this action is due to the free acid decomposing the alkaline phosphates,
which are necessary for the growth of the bacteria."

Qualitative tests for free liydrocMoric acid in gastric juice. — The
many colour tests for detecting the presence of free hydrochloric acid
in gastric juice, in contradistinction to organic acids, are all more or

1 " Lehrbucli der physiol. Chemie," 1894, Aufl. 3, S. 141-145.

^ Si(.'ber, Journ. f. irrald. Chem., Leipzig, 1880, Bd. xix. S. 433 ; Miqnel, Ccntrcdhl. f.
(dig. (hiidhts'pjUj., Bonn, 1884, Bd. ii. S. 403. See also Zienike, Inaug. Diss., Halle, 1893 ;
Mester, Ztschr.j. Idin. Med., Berlin, 1894, Bd. xxiv. S. 441 ; Schmitz, Ztsckr. f. fl)tisiol.
Chem,., Strassljuig, 1894, Bd. xix. S. 401.

^ " Experiences sur la digestion," Traduit par Senebier, Geneva, 1784.

^ Virdbows Archiv, 1883, Bd. xciii. S. 177.

^ Deutsche med. Wclmschr., Leipzig, 1884, JSTo. 20, S. 309.

" Nicati and Lietsch, liev. sclent., V&xis, 1884, p. 6.58 ; Covvpt. rend. Acad. d. sc, Paris,
1884, tome xcix. S. 928; Kocli, JJeulsche med. Wchnschr., Leipzig, 1884, No. 45, S. 725.

"^ Ztschr. f. physiol. Chem., Strassburg, 1890, Hd. xiv. S. 75.


less intlueiiced by the presence of proteicl or peptone, and cannot be
much depended on for proving the entire absence of hydrochloric acid.
The quantity of organic acid required to give the reaction in each case is
much in excess of that present in the stomach, so that if the test gives a
positive result this may usually be relied upon.

The best of these reagents are the following : — (a) Gunzherg's reagent,^
which consists of 2 parts of phloroghicinol, 1 part of" vanilHn, and 30 parts of
absolute alcohol. A few drops of this reagent and a few drops of filtered
gastric juice are evaporated to dryness together, when, if free hydrochloric
acid be present, a carmine-red mirror or carmine-red crystals are obtained.
The test is unaffected by organic acids, but does not succeed in the presence of
proteids or leucine ; it is said to detect 1 part of free acid in 20,000. (h) The
trojxeoUn ted. — Drops of a saturated solution of tropaeolin in methylated spirit
are allowed to evaporate on porcelain ; to the stain so left a drop of the solu-
tion to be tested is applied, and the drop is evaporated at 40° C. In the
presence of hydrochloric acid the result is a violet stain. The test has about
the same delicacy as Gunzherg's, and is subject to the same objections,
(c) Reoch's test ^ consists of a mixture of citrate of iron and quinine, and of
potassium sulphocyanide. This is coloured red by a trace of a mineral acid,
but not by dilute solutions of organic acid. Szabo '■^ has modified this test into
a quick, colorimetric quantitative method. He finds the Reoch test a satis-
factory one, unaffected by chlorides, peptones, or the usual amount of lactic
acid present in gastric juice. (d) Congo-red is strongly recommended by
Gamgee,^ either in aqueous solution, or as test paper made by saturating filter
paper with it, and then drying. Traces of hydrochloric acid turn it an intense
hlue, while organic acids give a violet tint.

Online LibraryE. A. (Edward Albert) Sharpey-SchäferText-book of physiology; (Volume v.1) → online text (page 51 of 147)