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cells of the gastric glands.^

Many have attempted to obtain indications of the nature of the
impulses passing along these nerves by artificial stimulation.

Eutherford*^ cut the vagi during digestion, and found that the mucous
membrane became paler. If the peripheral ends were stimulated, no
regular effect resulted ; if the central ends were stimulated, the mucous
membrane became redder. After division of both vagi, apparently
normal gastric juice was still secreted. Eutherford also found that
normal secretion occurred after division of the splanchnics. The effect
on the blood supply of stimulation of the central end of the vagus was,
presumably, brought about by impulses passing to the medulla oblongata,
inhibiting the action of the vasomotor centre there, and resulting in

^ The following is a list of the principal observations on gastric fistul?e in man : —
Helm, " Zwei Krankengeschichten," Wien, 1803; Brilcke's " Vorlesiuigen," Bd. i. S.
300; Beaumont (18'25-33), "Experiments and Observations on the Gastric Juice and the
Physiology of Digestion," reprinted from the Plattsburgh edition, Avith notes by Andrew
Combe, M.D., Edinburgh, 1838 ; W. Eobertson, 1851 ; C. Schmidt, Diss., Dorpat, 1851 ;
Ann. cl. Gheni., 1854, Bd. xcii. ; Kretschy, Jahresb. il. d. Fo7-tschr. d. Thier-Chem.,
Wiesbaden, 1876, Bd. vi. S. 173 ; Uffelmann, ibid., 1877, Bd. vii. S. 273 ; Richet, " Le sue
gastrique," Paris, 1878.

" The following is a list of the more important observations on gastric fistula? in
animals: — Bassow, Biill. Soc. imj}. d. nat. de Moscou, 1842, tome xvi. ; Blondlot, "Traits
analytique de la digestion," Nancy et Paris, 1843; Bardeleben, Arch. f. physiol. Heilk.,
Stuttgart, 1849, Bd. viii. ; Bidder u. Schmidt, "Die Verdauungssafte," Leipzig, 1852;
Holmgren, Jahresb. il. d. Leistnng. . . . d. ges. Med., Berlin, 1860, Bd. i. ; Schiff, " Lecons
sur la physiologic de la digestion," Paris and Berlin 1867, Bd. i. S. 15 ; Klemensiewicz,
Sitzungsb. d. k. Akad. d. JVissenach. , Wien, 1875, Bd. Ixxi.; Panum, Jahresb. it. d.
Fortschr. d. Thier-Chem., Wiesbaden, 1878, Bd. viii. S. 193; Heidenhain, A7-ch. f. d. qes.
Physiol., Bonn, 1878, Bd. xviii. S. 169; 1878, Bd. xix. S. 148; Hermann's "Handbuch."
Leipzig, 1881, Bd. v, S. 107.

* " Anlegung von Magenfisteln," Hermann's "Handbuch," Leipzig, 1881, Bd. v. Th. 1.

■* The details of this method are described by Chischin, Inaug. Diss., St. Petersburg, 1894.

^ Kytinanov, Internat. Monafschr. f. Anat. v. Physiol., Leipzig, 1896, vol. xiii. p. 402.

^ Trans. Boy. Soc. Edin., 1870, vol. xxvi.



538 MECHANISM OF SECRETION OF GASTRIC JUICE.

efferent impulses, dilator in character, passing along the sympathetic to
bhe mucous membrane.

That impulses passing along the vagi influence the movement of the
stomach, and possibly by that means to some extent the secretion, has
been shown by several observers.

Goltz ^ exposed the stomach and oesophagus of two curarised frogs,
and, after suspending them, dropped into their mouths salt solution. One,
however, had had the brain and spinal cord destroyed. After a time it
was found that in the complete animal the stomach and oesophagus were
widely distended, whilst in the pithed frog they were empty. The latter
result occurred equally well if the vagi only were cut. Stimulation of
the vagi peripherally caused only slight contractions. The explanation
given by Goltz of this result is that the stomach walls presumably
contain a local mechanism which, under the conditions in which the
animals were, would have undergone stimulation. The result of this
would havQ been peristaltic contraction, causing the fluid to be passed on
into the intestine. But ordinarily this is controlled by efferent impulses
passing from higher centres along the vagi. If the controlling influence
is destroyed, there results an exaggerated action of these centres. Goltz
was disposed to regard this local mechanism as of a ganglionic nature.

Ill connection with this question, it may be stated that OpencliOAvski ^ has
described the existence of special nerve-plexuses with ganglionic cells, both at
the cardia and at the pylorus. He considers that the opening and closing of
these passages are to be referred to the direct influence of these ganglia, though
these again are under the control of the central nervous system. Openchowski
describes a centre for the contraction of the cardia situated in the posterior
corpora quadrigemina, and connected with the stomach mainly by the vagi. A
centre for the opening of the cardiac orifice lies in the basal ganglia, and
communicates with the stomach by means of the vagus. There are also
subsidiary centres in the spinal cord influencing dilatation of the cardiac
orifice. In the same regions are centres influencing movements of the pylorus
and the intermediate walls of the stomach. Openchowski emphasises the
antagonism between the movements of the cardia and the pylorus ; such nervous
impulses as proceed down the vagus and dilate the cardiac orifice simultaneously
close the pylorus.

As regards the more direct influence of impulses proceeding along
the vPvgi upon secretion in the stomach, for a long time the greatest
uncertainty prevailed, and it was held that in general such impulses did
not directly affect secretion, but merely indirectly, through promoting
movements of the stomach walls. Heidenhain ^ has sug-gested that, as
mechanical irritation produced secretion from the digestive glands in the
plant Drosera, so the direct irritation of food in the stomach might
stimulate the gastric epithelium. There has existed for a long time,
however, indirect evidence of a flow of gastric juice resulting from
psychical conditions. Bidder and Schmidt '^ noticed, as early as 1852, that
the sight of food in a gastrostomised dog resulted in an abnormal flow of
gastric juice. To obviate any possibility of swallowed saliva causing
this result, which saliva it was known could be secreted as the con-

^ " Studien uber die Bewegnng von Speiserohre nnd Magen d. Frosche," Arch. f. d.
ges. Physiol., Bonn, 1872, Bd. vi.

- " Ueber die nervtisen Vorriclitungen des Magens," CcntralU. f. Physiol., Leipzig u.
W^ien, 1889, Bd. iii.

" Hermann's " Handbucli," Leipzig, 1881, Bd. v. Th. 1.

"* " Die Verdauungssafte nnd der Stotfweclisel," Leipzig, 1852.



I NFL UENCE OF NER VO US S YSTEM. 5 3 9

sequence of psychical conditions, oBSOphageal fistulpe were made, and the
saliva was prevented from passing into the stomach.

In Eichet's ^ observations on a human subject, who, by swallowing a
caustic alkali, had rendered the esophagus impassable, and in whom con-
sequently it had become necessary to make an opening into the stomach,
it was observed that chewing savoury food, none of which passed into
the stomach, produced a copious flow of gastric juice. It was not
possible in these cases to absolutely assert that this resulted from
nervous influence acting directly on the secreting epithelium, for move-
ments of the stomach may have brought about the flow, ]jut the quan-
tity secreted suggested a direct nervous influence. That there is such
a direct nervous influence has been conclusively proved by Pawlow,-
in conjunction with Schoumow-Simanowsky. Their experiments were
made on dogs which had had a portion of the stomach isolated in the
manner already described, care being taken that the nervous connections
were intact. In addition, the oesophagus was separated, the cut ends
being attached to openings in the neck, so that swallowed food passed
out at one opening, and, through the other, food which it was desired
should enter the stomach could be passed in. It was possible, therefore,
to bring the animal under the influence of food in three ways. In the
first place, it might be shown food, but the food would not be actually
introduced into the stomach. This constituted the so-called " psychical
feeding." ^ Secondly, the animal might be fed by the mouth, but none
of the food allowed to enter the stomach, since it would make its exit
at the oesophageal opening. This was described as " pseudo-feeding "
(Scheinftitterung). Thirdly, liy the introduction of food into the lower
division of the cesopliagus, true feeding was carried on. The results
varied according to the method adopted. The latent period, or period
elapsing after administration before secretion commences, is in the dog
about seven minutes. This does not vary much whether it be a case of
psychical, pseudo-, or true feeding. The latter course of secretion shows,
however, considerable variations. This was the first point established
by Pawdow.

He next attempted to discover the paths of the nervous impulses
bringing about these changes. Section of the splanchnics did not
affect the results, but after severing both vagi the reflex secretion
was absent. With one vagus cut (the right), the animal was found to
respond in the usual way. Later the left vagus was divided without
ansesthesia. The animals live for a few days in this condition, but
during this time no reflex secretion occurs. From this it was concluded
that the impulses constituting the efferent portion of the reflex act pass
along the vagi. But more positive results in this connection were
obtained by Pawlow by stimulating the peripheral ends of the cut vagi.
If, some twenty-four hours after the second section, the cut end be stimu-
lated, — and it is better to do this by applying induction shocks at the
rate of one per second, rather than by using the rapidly interrupted

1 " Le sue gastrique cliez riiomnie et les animaux," Paris, 1878.

"-' "Die Innervation der Magendrlisen beim Hunde," Arcli. f. Physiol., Leipzig, 1895.

^ Though the exhibition of food to the dog, Avhicb bad been operated on in the manner
described above, evoked a flow of gastric juice, if, from previous experience, the dog was led
to understand that the food would not actually be given, the secretion very soon stopped.
It may be mentioned that Heidenliain did not regularly obtain a flow as tlie result of
showing the animal food, and this suggests that his method involved interference with the
nervous tracts.



540 MECHANISM OF SECRETION OF GASTRIC JUICE.

current, — there results a flow of gastric juice. A certain interval occurs
before the secretion is manifest, which is to be referred to changes
actually taking place in the epithelium of the stomach. The character
of the secretion varies according to the stage of the digestive act and the
nature of the food. This will l^e again referred to in a later section.

It must be mentioned that some observers have not had the same success
in showing the secretory importance of the vagus nerve. That certain differ-
ences are perceptible in consequence of its excitation, they admit, but they
refer the variations rather to the altered power of muscular contraction
possessed by the stomach. Thus Leubuscher and Schaf er ^ experimented
both upon rabbits and dogs, performing the operations according to Pawlow's
method. They frequently used a control animal for precision in estimating
the change. As far as variations in the amount of hydrochloric acid were
concerned, they came to the conclusion that there was no constant difference.
The stomach they found invariably relaxed, and the food introduced within
was, after a prolonged interval, found to be arranged in two zones, one against
the walls of the stomach, which was well digested and contained hydrochloric
acid in normal amount, that occupying the centre of the viscus being poor in
acid and rapidly becoming decomposed. As far as stimulation of the peripheral
stump of the vagus was concerned, they did not obtain constant results, but
they appear to have adopted the rapidly interrupted current rather than the
induction shocks at prolonged intervals used by Pawlow. That the food was
not perfectly mixed, is obvious from their experiments. This will probably
explain the decomposition occurring ; this change was noticed also by Pawlow to
come on a few days after section of both vagi. It is, however, to be noted that
they were unable to confirm the passage of secretory impulses along the vagus.

There exists one observation upon the human being from which it seems
that stimulation of the vagus may cause a flow of gastric juice. Pegnard and
Loye - stimulated the vagus in a decapitated criminal some forty-five minutes
after death. Numerous drops of gastric juice appeared over the surface of the
stomach. This may also, however, have been the result of movements of the
stomach, which they observed at the same time to occur.

The conditions under ■which local stimulation provokes secre-
tion. — As already stated, it has been held by many that simple
mechanical irritation of the mucous membrane will directly produce a
flow of gastric juice. Beaumont ^ showed that mechanical irritation of
the mucous membrane caused increased vascularity and the appearance
of small drops of gastric juice, and he further pointed out that the effect
is confined to the irritated locality, and that the amount of juice secreted
is small in quantity. Tiedemann and Gmelin,* Heidenhain,'^ and
others also state that the secretion is limited. Pawlow*^ states that
the amount secreted is practically nothing, when indigestible substances
such as pebbles are placed in the stomach. It may therefore be
regarded as probably true that any secretion produced by simple
mechanical irritation is extremely small, and the existence of this sKght
secretion in no way suggests that the normal secretion can be looked
upon as the result, to any great extent, of such stimulation. On the
other hand, stimulation by food, even if solid, is much more effectual.

^ "Ueber die Bezieliungen des Nevvus Vagns zur Salzsaure-secretion des Magenschleim-
haut," Centralbl. f. mncre Med., Leipzig, 1894, Bd. xv.

" "Reeherches faites a Amiens sur les restes d'un supplicie," Compt. rend. Soc. de Mol..
Paris, 1887.

^ Op. cit. ■* Op. cit. " Arch. f. d. r/ps. Physiol., Bonn, 1879, Bd. xix,

^ Address at St. Petersburg. Reported in jiriL Med. Journ., London, 189.').



I NFL UENCE OF LO CAL STIMULA TION. 5 4 1

Heidenhain found that following a latent period of some fifteen minutes
after placing food in the organ, the stomach commenced to secrete gastric
juice. This delay beyond the interval observed in Pawlow's experiments
was presumably due to a certain amount of injury to the nervous
connections. If indigestible substances were swallowed, the secretion
was much longer delayed. The conclusion which Heideidiain arrived
at was that certain products of digestion when absorbed stimulate the
flow of gastric juice. The question then arises. What are these products
of digestion, and by what paths are they absorbed ? Are the completely
digested foodstuffs (that is to say, completely digested as far as gastric
digestion is concerned) passed on to the intestine and there al^sorbed,
or are they dkectly absorbed in the stomach ?

As regards the change undergone by different proteids when subject
to gastric digestion, there is reason to believe that the stage reached
in the stomach is not a final one, some further change taking place
in the duodenum, and that the amount of peptone formed in the
stomach may not be large, the proteose stage being, to a great
extent, the final stage of gastric digestion. If this is so, and if
the secretion from the gastric mucous membrane is influenced by
absorbed peptones, it must be influenced by peptones absorbed in
the small intestine. On the other hand, we are unable to state
definitely to what extent the intermediate results of the digestion
of proteids are alDsorbed in the stomach. As regards the carbohydrate
foodstuff's, V. Mering^ has shown that sugars are absorbed by the
stomach. If it is absorbed digestive products that provoke the
secretion, is it a specific product or products that cause this to occur, or
is it a common characteristic of all ? Chischin ^ has attempted to
answer this question. He finds that feeding a dog (which has had
a portion of its stomach isolated after the manner of Pawlow) with
different varieties of food, results in very different characters being
shown by the secreted juice during the course of digestion, and he
hence infers that there must be some specific stimulus or stimuH
influencing the secretion. The different substances were administered
in such a manner as to avoid the " psychical " influence on the secretion.
The administration of distilled water, gastric juice, or simple hydro-
chloric acid, caused but little change. Egg-albumin, sugar and starch
solution, were tested with the same negative results. The administra-
tion of peptone, however, resulted in a pronounced secretion. Chischin
considers that peptone was not only able to cause the gastric mucous
membrane to become active, but also to sustain it in activity. If egg-
albumin be administered so as to evoke the psychical influence, a well-
marked and sustained secretion resulted. Chischin accordingly explains
the usual process of secretion as occurring in the following manner : — At
the time of taking food the first flow of gastric juice is determined by
the reflex psychical influences involved in taking food. The digested
proteids are able later to evoke a secretion, at a time presumably
when the psychical influence begins to wane.

According to these experiments, then, we may assume that small
quantities of peptone may be normally formed in the stomach, and,

^ "Ueber die Function des Magens," Verhandl. d. Cong. f. innerc Med., Wiesbaden,
1893.

^ Inaug. Diss., St. Petersburg, 1894. Eeported in Jahresh. il. d. Fortschr. d. Tliier-
C'hem., Wiesbaden, Bd. xxv.



542 ME CHANISM OF SE CRE TION OF GASTRIC JUICE.

becoming absorbed there, in some way influence the epithehum so that
secretion results. The exact course of this absorption is a matter of
some difficulty as far as the secretory epithelium is concerned, but it is
yet more difficult to comprehend how peptone absorbed and changed in
the intestinal wall should influence secretion in the stomach. If, as
Schiff ^ long ago suggested, the absorption of these products should assist
in building up the precursor of pepsin, we could more easily see the
importance of these products passing to the secreting cells. Schiff,
however, emphasised dextrin as being pre-eminently a " peptogenous "
substance. Chischiu finds that it does not evoke secretion.

The conditions of formation of the ferments of the gastric juice.
— («■) Tlu conditions of the formation of 'pepsin. — As previously men-
tioned, Brucke ^ had noticed that the pepsin present in the gastric
mucous membrane was not yielded entirely to one extraction, and
Ebstein and Griitzner ^ pointed out that the peptic activity depended
considerably upon the manner in which an extract was prepared. An
extract made by treating the gastric mucous membrane with hydro-
chloric acid was much more powerful than one obtained by subjecting
the mucous membrane to the action of glycerin. That which was not
extracted by glycerin, Ebstein and Griitzner regarded as a compound
of pepsin with the proteid matter of the cells, this compound yielding
pepsin on subjection to the influence of acid, or to the action of sodium
chloride. Schiff* had also remarked, that if a dilute acid be added to
the stomach and left for some weeks, the extract becomes gradually
richer in pej)tic activity. Schiff accounted for this by assuming the
existence of a precursor of pepsin in the cells of the mucous membrane,
which gradually became converted into pepsin by the acid. This he
called ■propepsin. In both cases the observers were dealuig undoubtedly
with some substance which yielded pepsin, and to this substance the
name p)epsinogen has since been apphed. Ebstein's and Griitzner's
test for the existence of this substance was the fact that it was not
dissolved by glycerin as was pepsin, and yet would yield pepsin on
treatment with acid. But it was soon found that there were difficulties
in differentiating pepsin from its precursor in this manner. Von Wittich ^
pointed out that when fibrin is placed in a glycerin extract of pepsin,
the fibrin absorbs the pepsin, and will only yield it again to fresh treat-
ment with acid. Ebstein and Griitzner*' further showed that even
coagulated egg-albumin wTjuld do this. Thence it followed that the
proteids of the gastric mucous membrane might fix the pepsin, and that
a glycerin extract of the mucous membrane might be an extract of such
pepsin as was not fixed by the proteids. It was necessary, therefore, to
find some more definite test of the presence of pepsinogen. This was
supplied by Langley,'^ who found that sodium carbonate had a power-
fully destructive eft'ect on pepsin, but a much less marked action on
certain extracts of the mucous membrane from which pepsin could be
derived. These extracts, therefore, were held to contain the zymogen.
He also inferred that the gastric glands contained the ferment in the
zymogen state, as they did not contain any appreciable amount of

' "Leconssur la physiologic de la digestion," 1867, tome ii.
- " A'oiiesungen," 1874.

'■^Arch.f. d. (jcs. Physiol., Bonn, 1874, Bd. viii. '^ Ibid., 1877.

Ibid., 1872. Bd. v.; 1873, Bd. vii. « Op. cit.

'' "The Histology of the IMamnialian Gastric Glands, and the Relation of the Pep.sin
to the Granules of the Chief Cells," Journ. Physiol., Cambridge and London, 1882, vol. iii.



FORMA TION OF FERMFNTS OF GA STRIC JUICE. 543

pepsin, but would yield the same under appropriate treatment. The
differentiation of the one from the other was fiu'ther advanced Ijy
Langley and Edkins.^ They confirmed the o1)servation, that alkahes
and alkaline salts rapidly destroy pepsin. The conditions influencing
the rate of destruction by sodium carbonate were found to be the
strength of the solution of the alkaline salt, the time during which it is
allowed to act, the temperature of the mixture, and finally the amount
of proteids present. By mere neutralisation of an acid solution of
pepsin, a considerable amount might be destroyed. If equal volumes of
an extract of pepsin and of a 1 per cent, solution of sodium carbonate
were mixed, in fifteen seconds as much as 97 per cent, of the pepsin
might be destroyed. The greater the amount of proteid present, the
greater the amount of sodium carl3onate necessary to cause destruction.
The difference between pepsin and pepsinogen in their behaviour with
different reagents is merely one of degree. Pepsinogen is destroyed
also by alkalies, but the destruction is so slow as compared with that of
pepsin, that this reaction furnishes a useful method of distinguishing
the one from the other. Since the aqueous extract of the gastric
mucous membrane of a fasting animal loses but very little peptic
power on brief treatment with 1 per cent, sodium carbonate, it follows
that pepsinogen, but little or no pepsin, is present in the gastric glands
in hunger. Schiff stated that " propepsin " was slowly converted into
true pepsin. Langley and Edkins found that the conversion of
pepsinogen into pepsin is one of great rapidity. All the pepsinogen
present in an aqueous extract of a cat's gastric mucous membrane
may be converted into pepsin by treatment with 1 per cent, hydro-
chloric acid in sixty seconds. With reference to the point as to
whether pepsin is present in the gland cells during digestion, no definite
result was arrived at. Pepsin can be obtained from the gastric
mucous membrane of an animal in digestion, but not invariably, and
such as is found may have been produced by the acid in the lumen of
the tubes affecting the pepsinogen in the contiguous chief cells. In the
oesophagus of the frog, where no acid is secreted, but only ferment,
injection of commercial peptone causes no accumulation of pepsin in
the gland cells. Carbonic acid destroys pepsinogen more rapidly than
pepsin ; but if only a small quantity of peptone is present, there is
practically no destruction. Finally, it is observed that both pepsin and
pepsinogen are rapidly destroyed on heating to a temperature of 55°-
57° C.

(&) The conditions of formation ofremiin (^rennet-ferment). — An enzyme
which has the property of causing milk or the separated caseinogen
to undergo coagulation, is found in the stomachs of almost all animals.
As regards the secretion of rennin, there is an important resemblance
to that of pepsin, inasmuch as, in the case of the former, there is a
precursor of the actual ferment existent in the glands of the stomach
which has the power, under the influence of acid, of producing the
active enzyme. It was in the case of the rennin that it first was



Online LibraryE. A. (Edward Albert) Sharpey-SchäferText-book of physiology; (Volume v.1) → online text (page 77 of 147)