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Thougli tliere is diffirndty in admitting tlie existence of a controlling

^ Fran5ois-Franck.


centre for the pancreatic secretion in the semilunar ganglion, there is
even greater difficulty in associating such a centre with any other
neighbouring structure, or in admitting that, as Popielski considers, it
may be placed in the walls of the pylorus.

The conditions under which local stimulation provokes the
flow of pancreatic juice. — As stated in the last section, a secretion
of the pancreatic juice, dependent upon integrity of the nerve connec-
tions, can be brought about by the action of certain substances upon the
mucous membrane of the stomach or duodenum. Thus it was long ago
noticed that injection of ether into the stomach will cause a flow of
pancreatic juice, the juice having characters corresponding to the par-
ticular stage of digestion in which the flow is brought about.^ More
recently, other substances have been found to similarly affect the secre-
tion. If mineral acid, or even organic acids such as acetic and lactic,
be brought into contact with the duodenal mucous membrane, a secre-
tion will result. Since alkaline substances have not the same effect,
Dolinski^ considers that the acid products of gastric digestion bring
about their own neutralisation by inducing a flow of alkaline pancreatic
juice when they enter the small intestine. Dolinski also found that
fat excited reflexly a pancreatic secretion, and that alcohol was also
effective in this direction, but only to a moderate degree. Gottlieb^
agrees that reflexly induced secretion starts generally by stimulation of
the duodenal mucous membrane. Becker * studied the effect upon the
secretion of the introduction into the stomach of distilled water and
of various salts. The salts employed were various alkaline salts,
Carlsbad salts, sodium chloride, and " Essentouck " mineral water.
Becker found that distilled water exalted the secretion, whilst salts,
especially alkaline salts, diminished it, both in amount and in proteo-
lytic power. Sodium chloride in smaller doses was indifferent, in
larger doses it behaved as the alkaline salts. The better the
absorption the more marked the secretion. Water containing car-
bonic acid is more easily absorbed than simple distilled water, and,
correspondingly, the former excites a more plentiful secretion than the

We see, then, that the ordinary progress of the food can account for
the secretion normally appearing ; further, that the acid contents of the
stomach, when passed into the duodenum, may cause a powerful secretion,
and that alkaline salts in the stomach diminish the secretion.

The ferments of the pancreatic juice and their antecedents. —
Extracts made from the pancreas of many animals, and the pancreatic
juice obtained by the establishment of fistulee, possess the powder of
changing different foodstuffs. Heidenhain^ showed in 1875 that there
could be obtained from the pancreas a substance from which the proteo-
lytic ferment could be derived, but which did not actually possess
proteolytic activity. This substance he called " zymogen," but since we
are acquainted with substances having similar relations to other enzymes,
it is better to retain the name zymogen for the whole class, and to refer
each individual precursor by a name associated with the particular
ferment. We thus speak of the particular zymogen of the proteolytic
enzyme of the pancreas as trypsinogen.

1 Kiihne, " Lehrbucli der physiol. Cliera." " Op. cit. ^ Op. cit.

* Arch, cle sc. hiol., St. P^tersbourg, 1893, vol. ii.
^ Arch. f. d. (jcs. Physiol., Bonn, 1875, Bd. x.


Heiclenhain established definite characters distinguisliing tryxDsinogen
from the actual enzyme, and showed that in some resx^ects their behaviour
was similar. The chief relations of the zymogen to the ferment are as
follows : —

1. Trypsinogen is soluble in glycerin. Some glycerin extracts of
pancreas have no ferment activity, since the ferment is in the condition
of zymogen, but if such glycerin extracts, dissolved in 1 per cent,
sodium hydrate, be diluted with distilled but not boiled water (this
being largely devoid of dissolved air), especially if digested for a time
at 40° C, it will become active.

2. If an inactive glycerin extract of fresh pancreas be dissolved in
sodium carbonate, 1 to 2 per cent., the passing through it of oxygen
will cause the same to become active.

3. Platinmn black will, according to Podolinski,^ also render the
mert extract proteolytic.

4. The converse of the change brought about by the influence of
oxygen may also occur, for, through the deprivation of oxygen, acti^uty
becomes lost.

5. If fresh pancreas be mixed with the same weight of 1 per cent,
acetic acid for ten minutes, and then jDlaced in glycerin, a very active
extract will be obtained. The acetic acid converts the trypsinogen into
trypsin. According to Kuhne,^ trypsin is also formed from the zymogen
by warming with alcohol.

The amount of trypsin that can be obtained from an extract varies
with the histological condition of the gland. When the luminal zone
is of considerable width, a greater amount of proteolytic activity is
shown than when it is much reduced. We are justified in associating
the ferment with the granules seen in the cells.

Sodium carbonate may be regarded as an adjuvant to the action of
trypsin. Klihne ^ showed that it worked best in solutions of the strength
of 1 per cent. Edkins* proved that sodium chloride has a beneficial
influence on the digestion of fibrin by pancreatic extracts, and it may be
noted that a large amomit of the sodium carbonate associated with the
pancreatic secretion must be converted into sodium chloride in the
duodenum. Ewald^ states that digestion of fibrin at the instance of
trypsin can proceed in the presence of 0-3 per cent, of hydrochloric acid,
but, on the other hand, the prolonged action of dilute acids has been
shown by Langley ^ to be destructive of trypsin. If a glycerin extract
of pancreas be warmed for two and a half hours in 0-05 per cent, hydro-
chloric acid, its proteolytic powers are appreciably curtailed. The
diastatic ferment has not had the same study bestowed upon it as the
proteolytic. It contrasts with this latter in that there is no further
enhancement of its activity by treatment with such reagents as convert
trypsinogen into trypsin. Liversedge'^ made observations in 1874,
which suggested the existence of a diastatic zymogen, but the possi-
bility of micro-organic change influencing his experiments w-as, as
pointed out by Gamgee,^ not eliminated. According to his observations,

1 Breslau, 1876.

- Verhandl. d. naturh.-med. Ver. zu Heidelberg, 1876, N. F., Bd. i.

^ Ibid., Bd. i. * Journ. Physiol., Cambridge and London, 1891 Bd. xii.

^ Ztschr. f. klin. Med., Berlin, Bd. i.

^ Journ. Fluysifd., Cambridge and London, vol. iii.

"^ Journ. of Anat. and Pliysiol., London, 1874, vol. viii.

^ "Physiological Chemistry," vol. ii. p. 207.




























■— .

6 7 8 9 /O ri /2 /3 /4- 15 /6 // /<3 /f

Fig. 46. — Chart of the course of secretion of pancreatic juice.
The abscissfe correspond to hours ; the ordinates corre-
spond to c.c. of juice. — After Heidenhain.

the zymogen is not soluble in water, thus contrasting markedly with
other zymogens. We must regard the existence of a precursor in
this case as doubtful, though it is undeniably possiljle that in the
living cell an ante-
cedent state of the
ferment exists, adapted
to storage of the fer-
ment ; in that case the
mere destruction of the
cell might involve the
breaking dow^i of this
hypothetical zymogen,
on account of the pre-
cursor of the diastatic
ferment being less
stable than that of the

There is also no
evidence of any zymo-
gen of the fat-decom-
posing ferment, pialyn.
Finally, it has been
found that extracts of pancreas and the pancreatic juice itself^ have
the power of inducing a clot in milk, probably by the agency of some
specific enzyme in the juice.

The variations in the composition and. amount of pancreatic
juice during digestion. — From the earlier experiments of Bern-
stein,^ and those of
Heidenhain,^ it ap-
pears that the flow
of pancreatic juice
has somewhat the
following course : —
Before a meal
is over there com-
mences a secretion,
w4iich reaches a
maximum not later
than the third hour.
Then the secretion
sinks to about the
sixth or seventh
hour, and vet again
increases to the
ninth or eleventh ;
thence it sinks gra-
dually to about the








/ 2 J -f s e re 9 fo n tR. i^ 14 15 le n lefi

Fig. 47. — Chart of the percentage composition of the flow of
pancreatic juice. The abscissae correspond to hours ; the
ordinates to percentage of solids. — After Heidenhain.

eighteenth and twentieth. The quality of the juice varies inversely as
the quantity. When one rises the other falls. The accompanying
diagrams (Figs. 46 and 47) illustrate these variations.

^ Halliburton and Brodie, Jo%irn. Physiol., Cambridge and London, 1896, vol. xx.

^ Op. cit.

^ Hermann's " Handbuch," Bd. v.


It has been pointed out by Mette that during normal digestion there is a
certain indejDendence between tlie secretion of ferment and the secretion of water.
Observations have also been made by Wassilieff ^ on the influence of food in
causing changes in the activity of the juice. He found that the maximum of
secretion was in the first two hours, with meat diet in the first hour, and
milk diet in the second hour. By changing the diet from meat to bread and
milk, the proteolytic action of the juice diminished, whilst the diastatic action
remained unaltered. On the other hand, when changing from bread and
milk to meat, these were reversed. It is therefore to be noted that the
relative quantity of both ferments is variable and dependent upon the food.
The effects produced by other substances upon the flow of pancreatic juice
have already been mentioned (p. 551).

The Mechanism of Seceetion of Succus Entefjcus.

The histological evidence of secretion in the intestine. — The

evidence of secretion from the histological standpoint is, in the case of
the mucous membrane of the intestine, very incomplete. Paneth^ pointed
out that the cells at tlie base of the crypts of Lieberkiihn frequently
contain definite granules. These cells were also studied by Nicolas,^
who noticed different phases in the condition of the cells ; thus, after
secretory activity, he found them either free from or containing but
few granules.

Hardy and Wesbrook * found that in fasting animals the granules
were large and numerous, in well-fed animals comparatively few, and
smaller than in the fasting state.

Bizzozero ^ regards the granules as mucigen granules. Schaffer ^
has also called attention to the fact that the cells containino; them
are goblet - shaped. From the manner in which they stain, their
shape, and the fact that they are scattered in the crypt of Lieberkiihn,
it seems probable that they are to be looked upon as mucus-secreting

The cells covering the villi have been described by Nicolas ^ as con-
taining granules which do not stain, or at the best very slightly, with
safranin (unlike those just referred to). He states, however, that these
granules give rise to some secretion. Examined in the fresh state,
the cells do not show the existence of typical secretory granules.

Brunner's glands, from their structure, suggest the formation of
a mucous secretion,^ but it has been stated by Krolow ^ that an extract
of the glands will digest fibrin in acid solution, and they bear
considerable resemblance, histologically, to the pyloric glands of the

The experimental evidence of secretion of succus entericus.—
Two methods have been adopted for obtaining evidence as to the
nature of succus entericus. The first consists in isolating, by operation,
a piece of the intestine, and observing the nature of the liquid which

1 Arch, de sc. biol., St. Petersbourg, 1893, vol. ii.

"Arch./, mikr. Anat., Bonn, 1888, Bd. xxxi.

" Internat. Monatschr. f. Anat. u. Physiol., Leipzig, 1891, Bd. viii.

■^ Journ. Physiol., Cambridge and London, 1895, vol. xviii.

'^ Anat. Anz., Jena, 1888, Bd. iii. ; Atti d. r. Acad. d. sc. di Torino, 1888-9.

" Sitzungsh. cl. k. Akad. d. Wissensch., Wien, 1891, Abth. 3, Bd. c.

"^ Op. cit.

** Kuezynski, Internat. Monatschr. f. Anat. u. PJn/siol., Leipzig, 1890, Bd. vii.

•' Berl. klin. JVchnschr., 1870, No. 1.


collects in the interior ; the second, in making extracts of the intestinal
mucous membrane and investigating the digestive properties of such an

A method of permanently isolating a portion of the intestine was
first devised by Thiry.^ The abdomen of an animal having been opened,
a piece of intestine was cut away from its continuity with the main gut
without dividing the mesentery. The two ends of the main gut were
then brought together and ligatured, so that union of the cut surfaces was
brought about, the continuity of the intestine being thus re-established.
The isolated portion of the gut was then closed by a ligature at its lower
end, while the upper end was sewn into the incision in the abdominal
wall, a blind sac being thus formed. Vella ^ modified this procedure by
inserting the lower end of the isolated gut also into the abdominal wall ;
thus affording two openings for the separated intestine. This operation,
performed with due antiseptic precautions, is of constant service at the
present day, and is generally described as the establishment of a
" Thiry- Vella " fistula.

Older observers, such as Bidder and Schmidt,^ had ligatured off from
the general tract short lengths of the intestine, and, after replacing them
in the abdominal cavity for some hours, had examined the accumulated

The chief facts that have been brought to light by these methods
are as follows : — In the absence of any stimulus, little or no secretion
has been obtained, as a rule. Thiry,* with mechanical or electrical
stimulation, obtained a thin yellowish alkaline secretion, albuminous in
character. After food had been taken, although no previous secretion
was manifest, some fluid began to form. According to Eohmann,^ the
introduction of starch, sugar, or peptone provokes intestinal secretion.
The administration of pilocarpine results, according to Masloff,*^ in
secretion. Gamgee,'^ however, found that it was possible to produce
considerable increase of other secretions by the administration of
pilocarpine without affecting the succus entericus to any extent. This
result he attributed to the fact that probably different regions of the
intestine reacted with different vigour to pilocarpine, the lower portion
of the intestine secreting a greater quantity than the upper.^

With respect to the existence of nervous influences on the secretion,
Thiry found no result to come about from stimulation of the vagi.
Budge ^ and Lamansky ^° obtained increase of secretion after extirpation
of the cosliac and mesenteric plexuses, but Adrian ^^ did not succeed in
obtaining this increase. Brunton and Pye-Smith ^^ found, in confirmation
of an oliservation of Moreau,^^ that if all nervous connections l^e severed

^ " Eine nene Methods den Dunndarm zu isolieren," Sitzungsb. cl. k. Akad. d. Wissensch.,
Wien, 1864, Bd. i.

- Untersuch. z. Natxtrl. d. Mensch. u. d. Thieve, 1881, Bd. xiii.

^ "Die Verdauungssafte und der Stoffweclisel, " Leipzig, 1852. ^ Op. tit.

° Arch. f. d. ges. Physiol., Bonn, 1887, Bd. ii.

^ Untersuch. a. d. iihysiol. Inst. d. Univ. Heidelberg, 1882, Bd. ii.

■^ "Physiological Chemistry," London, 1893, vol. ii.

^ That pilocarpine provokes an intense secretory charge in the crypts of Lieberkiihn of the
large intestine, is manifest from the experiments of Heidenhain (Hermann's "Handbnch,"
Bd. v.).

'^ Verhandl. d. k. k. Leopold-Carol. Acad. d. Naturforscher., 1860, Bd. xix.
10 Ztschr.f. rat. Med., 1866.

^1 Beitr. z. Anat. v.. Physiol. {Eckhard), Giessen, 1863, Bd. iii.
^- Rep. Brit. Ass. Adv. Sc., London, 1874, 1875, 1876.
^■^ Compt. rend. Acad. d. so., Paris, 1863, Bd. Ixvi,


between higher centres and the mucous meml^rane liy dividing the
intestinal nerves, an accumulation of fluid takes place. Brunton and
Pye-Smith also foimd that if the inferior ganglia of the solar plexus and
their continuation along the superior mesenteric artery are left in con-
nection with the gut, this accumulation does not take place.

L. Hermann ^ initiated a somewhat different method of investigating
the secretion. A loop of intestine was separated from the main gut, and
its ends joined so as to form a confluent ring. This was replaced in the
intestine, and its contents examined after some weeks. These contents
were found to consist of solid material, and it was presumed that this
represented the inspissated juice. Blitstein and Ehrenthal ^ continued
these experiments, and came to the conclusion that the solid mass found
had its origin in two sources ; the first being the intestinal fluid, and the
second detached intestinal epithelial cells. They noticed micro-organisms
also to be j)resent. Fr. Voit,^ who simply sewed up the ends of an iso-
lated loop, found, after the lapse of three weeks, a yellowish-grey mass, in
which he recognised no epithelium, and which he regarded as simply
inspissated juice. The natm-e of the fluid excreted in the Thiry-Vella
loop has been frequently examined. It is of a yellowish colour, and
contains albumin, and also a rather large amount of sodium carbonate.
It possesses certain ferment-powers, though with regard to these there
is considerable divergence of statement. Thiry* found it to dissolve
fibrin, but not to affect other proteids. Masloff ^ found it to act feebly
on starch, but not on proteids.

Funke*^ stated that starch injected into isolated loops is not con-
verted into sugar. Later observers,'' experimenting by the above
methods, agree that starch is converted into sugar, and Piohman's
experiments suggest a greater diastatic activity in the upper part of the
intestine than the low^er. This observer also finds, as Paschutin^ had
previously pointed out from experiments with extracts, that the
intestinal juice has the power of inverting cane-sugar. It is to be noted
that this is, even markedly, the case, as Gamgee ^ points out, in animals
which would have no opportunity, from the nature of their food, of
utilising the enzyme causing such a change. Observations made recently
by Pregl ^^ on a Thiry-Vella fistula established in a lamb, have somewhat
completed the knowledge that has accrued from this method of research.
He found that the secretion was continuous, but it increased the first hour
after food, and this went on to about the third hour. From a length of
intestine of 72 cm. he obtained about 5 grms. of intestinal juice per hour;
this rate of secretion diminished to the fifth hour, when it reached 3 grms.
per hour, and remained at this rate for many hours after. He refers to
the prolapse which occurs at first, and with which other observers have
found difficulty, and points out that this is evidence of a catarrhal condi-
tion, which itself would accomit for a certain amount of flow, although he
failed to notice any difference between the juice reinforced by catarrhal

1 Arch.f. d. ges. Physiol., Bonn, 1889, Bd. xlvi.

- Ibid., 1891, Bd. xiviii. ■■ Ztschr. f. Biol., Miluehen, 189-3, Bd, xxix.

'' Op. cit. ■' Op. cit. « "Lehrbuch."

^ Gumilewski, Arch.f. d. ges. Physiol., Bonn, 1886, Bd. xxxix. ; Rohmann, o/j. cit. ;
Dobroslawin, " Beitr. z. Physiol, d. Darmsaftes," Untersivch. a. d. Inst. f. Physiol, it.
Histol. in Graz, Leipzig, 1870 ; Lannois et Lepine, Arch, de physiol. norm, et path.,
Paris, 188.3.

^ Arch. f. Anat. u. Physiol., Leipzig, 1871. " Op. cit.

i» Arch.f. d. ges. Physiol., Bonn, 1896, Bd. Ixi.


exudation and the simple juice. Pilocarpine, he found, did not cause
increased secretion, nor did electrical stimulation. He describes the
juice as consisting of a yellow fluid, in which are suspended flocculi,
staining deeply with eosin, and mainly mucous in nature. The alkalinity
is marked. Albumin and globulin are present, and what he regarded as
probably albumose. He also found a small amount of urea. The secre-
tion had no action upon proteids. From starch paste was formed after
twenty-four hours a fermentable sugar. This action was shown more
powerfully in the earlier than the later months after the operation.
Eaw starch was not affected. He found that dextrose (not maltose) was
formed both from starch and glycogen. No fat-splitting action was
manifest, but the juice easily emulsified fat. The loop experimented
upon was found to be situated about three times as far from the stomach
as from the large intestine. Pregi calculates that the whole intestine
would secrete nearly 3 litres in twenty-four hours.

It is difficult to say to what extent we are justified, from experiments
performed on isolated loops, in forming conclusions regarding the nature of
normal succus entericus. The first question that suggests itself is, How far
is the fluid secreted a catarrhal production % As above stated, Pregl has
pointed out that the mere prolapse of the gut causes a catarrhal increase above
what he regards as the ordinary flow. The facility with which micro-organisms
could enter would tend to increase any pathological condition. The presence
of albumose in a fluid which does not digest proteid, and also of urea, suggests
a pathological condition. Many of the ferment powers attributed to the
juice might be due simply to desquamated epithelium from the Avails of
the loop.

Klecki 1 has criticised in the same Avay the experiments of L. Hermann,
Blitstein and Ehrenthal, and Voit, dwelling on the abnormal conditions of the
loop, and the small number of experiments upon which their conclusions are
based. He himself finds that Avlien few micro-organisms are allowed to remain
in the gut, much less solid substance is finally found, and states that a large
amount of contents is found in Hermann's rings only when the intestinal wall
shows pathological changes, or if complete disinfection of the loop has not
been carried out.

It would seem, therefore, that we must hesitate before accepting all the
conclusions that have been drawn from the employment of the methods of
isolated loops and Thiry-Vella fistulee, bearing in mind that the juice so
obtained is probably seldom entirely uninfluenced by the abnormal condition
induced by the operation. Many, however, regard it as probable that the
crypts of Lieberktdm, through their lining epithelium, yield a secretion
which is of assistance in dissolving the products of digestion by other juices,
even if it has no very well-marked digestive properties itself.

We may finally proceed to consider how far extracts made from
the intestinal wall are characterised by the possession of specific

In the first place, we must bear in mind that the intestinal mucous
membrane has primarily, without doubt, an cibsorhing function. We
have also reason to believe that the digested food in its passage through
the epithelial cells may undergo considerable changes. Consequently, on
making extracts of these epithelial cells, we may be separating substances
which are never secreted into the lumen of the intestine, but which
merely exercise influence on the absorbed food as it passes through the
^ Wien. Mill. WcJmschr., 1894, Bd. vii.


cells. It is, therefore, not justifiable to assume that the secreted
juice has the same action as an extract of the intestinal mucous

Online LibraryE. A. (Edward Albert) Sharpey-SchäferText-book of physiology; (Volume v.1) → online text (page 79 of 147)