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

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^ See Corvisart, "Collection de m<^moires sur iiiie function peu connue du pancreas, la
digestion des aliments azotes," Paris, 1857-8, p. 41 ; Meissner, Ztschr. f. rat. Med., 1859,
3 Reihe, Bd. vii. S. 17 ; Klthne, VerJiandl. d. naturh.-med. Vcr. zu Ecidelherg, N. F.,
Bd. i. S. 190 ; Danilewski, VircJiow's Archiv, 1862, Bd. xxv. S. 291 ; May, Untcrsuch. a. d.
physiol. Inst. d. Univ. Heidelberg, 1880, Bd. iii. S. 378 ; Lindberger, Jalircsb. u. d. Fortschr.
d. TUer-Ohem., Wiesbaden, 1883, Bd. xiii. S. 280; Ewald, Ztsclir. f. Jclin. Med., Berlin,
1880, Bd. i. S. 615 ; Langley, Journ. Physiol., Cambridge and London, 1880-2, vol. iii.
p. 262.

2 Weiss, Firchmv's Archiv, 1876, Bd. Ixviii. S. 413 ; Meker, Inaug. Diss., Erlangen,
1894. According to the latter author, a digestion which is complete in two and a half
hours with 1 per cent. ]Sra.,C03 is incomplete in twenty-four hours with either 3 per cent.
Na^Co., or O-QIO per cent'of HCh

^ Chittenden and Cummins, Stud. Lab. Physiol. Chem., New Haven, 1885, vol. i. p. 100.

■» Hermann's "Handbuch," Bd. v. (1), S. 187.

* Podolinski, " Beitr. z. Kenntnlss des pankreatische Eiweissfermentes, " Breslau, 1876,
S. 43. See also Chittenden and Cummins, loc. cit., who found that borax and potassium
cyanide augment, while salts of mercury and iron decrease, the activity.

"Lindberger, Jahrcsb. ii. d. Fortschr. d. Thier-Chem., Wiesbaden, 1883, Bd. xiii.
S. 280; Schafcru. Bohm, ibid., 1872, Bd. ii. S. 363; Ivllhnc, Verhandl. d. naturh.-med.
Ver. ::u Heidelberg, IST. F., Bd. i. S. 190.


states that pancreatic diastase is capable of converting 40,000 times
its weight of starch into maltose and dextrin ; Kroger, that 1 grm. of
pancreatic juice, containing 0'021 grm. of dry solid, of which in turn
only a small fraction could be amylopsin, digested in half an hour 4"67
grms. of starch.

Influence of temperature. — The rate of conversion increases with
rising temperature from 0° C. to 30° C; from 30° C. to 45° C. the rate
is at a maximum and practically constant. Above 45° 0. the action
becomes slower with rising temperature, and ceases between 60° C. and
70° C, the ferment being here destroyed.^

Influence of reaction. — Pancreatic diastase closely resembles salivary
diastase in its behaviour to change in reaction of the medium in which
it is dissolved. It seems to act best when neutralised or in presence
of minute traces of. acid ; but a limit of acidity is soon reached beyond
which the rapidity of action rapidly diminishes, and the enzyme itself
is quickly destroyed.^ The optimum activity, according to Melzer's
measurements, coincides with the presence of O'Ol per cent, of hydro-
chloric acid.

Pialyn.— Very little is known of the fat-splitting enzyme, pialyn, of
the pancreatic juice. That the action is due to an enzyme is shown
by the following experimental observations : — (a) The action is de-
stroyed when the pancreatic juice or active pancreatic extracts are
boiled ; (&) it takes place in presence of antiseptics, and hence cannot
be due to bacteria.^

The enzyme is much less stable than either of the other two
associated with it in pancreatic juice. It is especially susceptible to
the action of acids, being quickly destroyed by all except the higher
fatty acids, so that great care to avoid acidity of solution must be
exercised in the preparation of it from the pancreas. Paschutin*
recommends for its extraction a dilute solution of sodium carbonate
and bicarbonate in water, and Griitzner ^ that it should be extracted
from the perfectly fresh pancreas with a solution containing 90 c.c. of
glycerin to 10 c.c. of 1 per cent, sodium carbonate, ten times the weight
of gland to be extracted being taken of this fluid. However extracted,
it must he taken from afresh gland and not from one which has stood over
a day, as in the case of the other two enzymes, for thereby an acid reaction
would be developed, and as a consequence the fat-splitting enzyme would
be destroyed.

The rapidity of action of the enzyme is at first increased by rising
temperature. It acts almost twice as fast at 38° C. as at 18° C, but it
is destroyed by boiling ; the temperature of destruction is not accurately

It acts more slowly in the presence of 0*2 5 per cent, of sodium
carbonate than in neutral solution.

Its activity is greatly increased by the presence of bile, still more
by a mixture of bile and hydrochloric acid ; this increase in activity is
due to the bile salts or bile acids, which have a similar effect. The
rapidity of action of the enzyme is usually much underrated, and it

^ Roberts, " Digestion and Diet," London, 1891, p. 74 ; Proc. Roy. Soc. London, 1881,
vol. xxxii. p. 145.

^ Melzer, Inaug. Diss., Erlangen, 1894.

^ Nencki, Arch. f. exper. Path. u. Pharmakol., Leipzig, 1886, Bd. xx. S. 367.

■* Arch.f. Anat. it. Physiol., Leipzig, 1873, S. 386.

s Arch.f. d. gcs. Physiol., Bonn, 1876, Bd. xii. S. 302. .


is probable that it is capable of splitting up all the fat of a full meal
in the ordinary time of digestion within the body.^

Pialyn acts on other esters than the neutral fats causing a similar

Separation of the pancreatic enzymes. — There has, strictly speak-
ing, been no complete isolation of the pancreatic enzymes obtained by
the various workers on the subject. Partial success has been so far
obtained, in that methods have been invented which yield solutions
much richer in one of the two principal enzymes than in the other.

Danilewski ^ was the first to tackle this difficult task, under the direction
of Kiihne. He found that, after shaking up a watery infusion of the
pancreas of the dog Avith excess of magnesia, and filtering, there remained an
infusion which possessed only a proteolytic and diastatic action.

This sokition was mixed up with one quarter of its volume of thick collodion
solution (in alcohol and ether), and thoroughly shaken. The collodion is
thrown out of solution, as a pasty mass, which mechanically carries with it
the proteolytic ferment, while the diastatic ferment remains in solution.
The collodion is removed, washed, and dissolved in a mixture of alcohol and
ether. This solution is allowed to stand for some days, when the proteolytic
ferment with a little proteid falls to the bottom as a yellow sediment. This
, sediment, when dissolved again in water, digests fibrin in alkaline or neutral,
not in acid solution. The filtrate from the collodion, which contains the
diastatic enzyme, is evaporated down in vacuo, and filtered from anything
which precipitates out. The filtrate is precipitated by excess of absolute
alcohol, extracted by a mixture of 2 parts water to 1 part alcohol, and
dried in vacuo. The solution so obtained rapidly converted starch into
sugar, and only possessed a very feeble action on fibrin. Lossnitzer ^ has
repeated these experiments, and only partially confirms them. ^Neither of
the two products obtained by Danilewski gave the xanthoproteic, or Millon's

Cohnheim ^ obtained the diastatic enzyme from an infusion of pancreas, by
a method identical with that by which he obtained ptyalin.^ This substance
possessed no proteolytic action, did not give the proteid reactions, but acted
very energetically on starch.

V. Wittich '^ made use of the insolubility of trypsin in dry glycerin to
obtain an extract rich in diastatic ferment and free from proteolytic action.
The pancreas is dehydrated in strong alcohol, and further allowed to stand
under absolute alcohol for some time ; the tissue is then dried and extracted
with dry glycerin ; the extract after filtration is precipitated by excess of
alcohol, and the precipitate is again extracted with dry glycerin. In this
manner v. Wittich obtained an extract which did not act on fibrin and had
an intense action on starch. Hiifner got an extract, on repeating the process,
which also contained trypsin ; but as Kiilme states that trypsin is not soluble
in glycerin, Hiifner's results may be due to water in the glycerin em-

Paschutin^ attempted to separate the pancreatic enzymes by using as

^ All these ob.servations on the rapidity of action of this enzyme, and its variations,
have been made by Rachford, Journ. Physiol., Cambridge and London, 1891, vol. xii.
p. 72.

2 Berthelot, Ann. d. chim., Paris, 1854, tome xli. p. 272 ; Nencki, Arch. f. exper. Path,
u. Pharmakol., Leipzig, 1886, Bd. xx. S. 367 ; Baas, Ztsch7\ f. physiol. Chem., Strassbnrg,
1890, Bd. xiv. S. 416.

3 Firchow's ArcMv, 1862, Bd. xxv. S. 279.

•^ Arch. d. Heilh., Leipzig, 1864, Bd. v. S. 556.

s Virchow's Archiv, 1863, Bd. xxviii. S. 241. " See p. 328.

"^Arch.f. d. ges. Physiol., Bonn, 1869, Bd. ii. S. 198.

^ Arch. f. Anat. u. Physiol,, Leipzig, 1873, S. 382.


extractives concentrated solutions of different salts. He fonnd that some salt
solutions extracted all three ferments, while others especially extracted one
ferment accompanied by traces of the others. Thus sodium chloride, sodium
sulphate, and potassium chlorate extracted all three ferments indifferently ;
sodium bicarbonate, with a little of the normal carbonate added, extracted best
the fat-splitting ferment ; the proteolytic ferment was taken up best by
potassium iodide, arsenite, or sulphite ; and the diastatic ferment by
potassium arsenate alone or with the addition of ammonia.

Dastre ^ has recently described methods for approximately separating the
proteolytic and diastatic enzymes of the pancreas.

1. If the pancreas of an animal killed during digestion be cut into large
pieces, and these then digested for 15-20 minutes at 40° C, in normal saline
(•7 per cent.), the filtrate is found to possess a strong diastatic action, but
scarcely any proteolytic action. If, after this first extraction, the pieces are
finely minced and extracted anew with normal saline (1 per cent, of sodium
fluoride being added to prevent putrefaction), an extract is obtained rich
in proteolytic ferment, but containing scarcely any diastase.

2. On extracting a fresh gland with alcohol of increasing strength, after-
wards with ether, and drying over sulphuric acid, a powder is obtained
which yields, on extraction with saline, a fluid Avhich is almost inert towards
starch, but is actively proteolytic.

3. An extract made from the pancreas of an animal which has not been fed
for some days, contains proteolytic ferment but has scarcely any diastatic action.

The Intestinal Enzymes.

Practically nothing is known of the enzymes of the small intestine
save their action on foodstuffs ; none of them have been obtained in
even approximately pure condition, and the fact that there are enzymes
rests on the observations — (1) that the action is destroyed by boiling,
and (2) that it takes place under antiseptic conditions. Until the
importance of this latter condition was demonstrated by the work of
Kiihne on pancreatic digestion, there was much difference of opinion
as to whether the succus entericus contained a proteolytic enzyme
or not ; some observers had observed digestion of proteids by this
fluid, and others had been unable to do so. At length it was shown
by Masloff^ and by Wenz ^ that when precautions are taken to
prevent bacterial growth, the succus entericus or extracts of the
intestinal mucous membranes have no action on proteids or on

With regard to the action of succus entericus on carbohydrates, the
more recent work on the subject all goes to show that starch is con-
verted into maltose, maltose into dextrose, and cane-sugar into dextrose
and Ipevulose, both by the succus entericus and by extracts of the
intestinal mucous membrane.

The succus entericus contains no enzyme which acts on neutral fats.
The power of emulsifying fats, which was occasionally observed by the
earlier workers on the subject, was doubtless due to the alkalinity of the

^ Co'ni'pt. rend. Soc. de hiol., Paris, 1893, tome xlv. p. 648 ; Arch, defliysiol. norm, etpath.,
Paris, 1893, tome xxv. p. 774.

^ Untcrsnch. a. d. physiol. List. d. Univ. Heidelberg, 1882, Bd. ii. S. 920. Masloff
found very slight action of the juice when acidified, probably due to infiltrated pepsin.

^ Ztsehr. f. Biol., Mlinchen, 1886, Bd. xxii. S. 1. This result is coniirraed by the
observations of Tubby and Manning on human succus entericus, Guy's Hosp. Rep., London,
1891, vol. xlviii. p. 277.


fluid, aided by the presence of free fatty acid in the fat used for the

Paschutin ^ attempted by two different methods to separate the
diastatic and inverting ferments : —

1. An infusion of tlie intestinal mucous membrane was made by rubbing
it lip with water and powdered glass, and filtering. When this infusion was
mixed with a solution of collodion, the precipitated collodion brought down
most of the inverting enzyme, and most of the diastatic enzyme was left in
solution, but only a partial separation could be effected in this manner.

2. The mucous coat of a piece of intestine Avas freed from the other coats,
and then water was filtered through this, under pressure. The fluid which
filtered through acted energetically on starch, but had no action or only a
very feeble one on cane-sugar.




The saliva is a mixture in varying proportions of the secretions
of the different salivary glands. As these secretions differ from
one another considerably in chemical composition, it will be well
to consider first the physical and chemical nature of each of them
in turn, and afterwards that of the fluid which results from their

Submasillary saliva.— Submaxillary saliva may be obtained by in-
serting a fine cannula into the opening of Wharton's duct. In some
individuals Wharton's duct carries to the mouth the secretion of the
submaxillary gland only, in others the duct of Bartholin leads into
Wharton's duct, when the latter conducts the mixed secretion of the
submaxillary and sublingual glands to the mouth. The tongue should
be raised, but not too high, the cannula carefully inserted and gently
pushed into the duct for about an inch. By this procedure the end of
the camiula is thrust past the opening of the duct of the sid3lingual
gland, in case both glands share a common duct, and so the obtaining of
submaxillary saliva only is ensured.^

Human submaxillary saliva is a clear, watery, mobile fluid, which
becomes viscid on standing in contact with air, and deposits flocculi.
It is always alkaline in reaction. On boiling, it becomes cloudy, and
the cloudiness is increased by the addition of acid. Its specific gravity
varies between 1-0026 and 1-0033, and is lessened by hunger. The
amount of total solids lies between 0-36 and 0"46 per cent., and is not
much influenced l^y food. According to Eckhard, it contains no
sulphocyanates, while Oehl and Sertoli* state that it contains them,
but in less amount than the secretion of the parotid. Colorimetric

^ See, however, SchifF, Arch, dc ])}iysiol. norm. ctjiaiU., Paris, 1892, tome xxiv. p. 679.
Schiff liere repeats his earlier statements, that succus entericus acts both on proteids and
neutral fats. Prege {Arch. f. d. ges. Physiol., Bonn, 1896, Bd. Ixi. S. 3.59) has recently
obtained succus entericus from a Vella fistula in the sheep, and determined that it has no
action on proteids or neutral fats.

^Arch.f. Anat. u. Physiol., Leipzig, 1871, S. 305.

2 Eckhard, Jahresb. u. d. Fortschr. d. gcs. Med., Erlangen, 1862, Bd. i. S. 126; cited
from Maly, Hermann's "Handbuch," Bd. v. (2), S. 17.

* Oehl, Jahresh. il. d. Fortschr. d. ges. Med., Erlangen, 1865, Bd. i. S. 120 ; Sertoli,
ibid., 124.


measurements gave for the submaxillary saliva 0'004 per cent., for
the parotid 0'03 per cent., of this substance, reckoned as potassium
sulphocyanate. It contains ptyalin, as shown by its powerful diastatic
action on starch.

The submaxillary saliva in the dog contains much more mucin than in
man, and is in consequence much more viscid. It is alkaline in reaction, 100
grms. requiring for neutralisation 0'135 to 0"144 grms. of sulphuric acid,
reckoned as SO3. On standing in contact with air, calcium carbonate is
thrown down as a flocculent precipitate, which was previously held in solution
by the dissolved carbon-dioxide as bicarbonate. The same result is brought
about more rapidly by heating. It contains, at most, only traces of proteid
or of sulphocyanate. Its specific gravity is 1'0026 to 1"004.

The quantitative composition of the saliva obtained on stimulation of
the submaxillary gland varies according to the nerve stimulated. The
saliva obtained on stimulation of the sympathetic (sympathetic saliva)
is scanty in quantity, and contains much mucin, which gives it a viscid
consistency. Chorda saliva, on the other hand, is plentiful in quantity,
contains less mucin, and is hence a thin watery fluid. The chorda saliva
has a specific gravity of 1-0049 to 1-0056, and contains 1-2 to 1-4 per
cent, of total solids; sympathetic saliva has a specific gravity of 1-0075
to 1-018, and contains 1-6 to 2-8 per cent, of total solids.^

Parotid saliva. — Human parotid saliva may be obtained by intro-
ducing a fine cannula into Stenson's duct.^

It is a thin, mobile fluid, usually clear, sometimes somewhat turbid,
and contains no formed element save epithelial cells. It is alkaline in
reaction, but the first few drops secreted may be neutral or acid,
especially in a state of hunger ; in all cases the alkalinity is less than
that of submaxillary saliva.^ Its specific gravity seems to be very
variable (Mitscherlich, 1-006 to 1-008; Oehl, 1-010 to 1-012 with scanty
secretion, 1-0035 to 1-0039 with plentiful secretion; Hoppe-Seyler,
1-0061 to 1-0088); the amount of total solids lies between 5 and 16
parts per thousand. It contains traces of proteids, but is free from
mucin ; it also contains ptyalin and sulphocyanate.

The parotid saliva of some animals, such as the dog and horse, is very
rich in calcium bicarbonate, and often deposits crystals of calcium
carbonate on standing.^ Stimulation of Jacobson's nerve in the dog
produces a flow of saliva from the parotid, poor in organic constituents.
If, before this is done, the cervical sympathetic be stimulated, which
alone produces no effect, on now stimulating the nerve of Jacobson
a flow of saliva is obtained which is much richer in organic con-

Sublingual saliva.— Oehl attempted to obtain human sublingual
saliva by a similar method to that described in the case of the other two
glands ; he was only able to obtain a very small quantity, insufficient for

^ Eckhard, BeAtr. z. Anat. u. Physiol. (Eckliard), Giessen, 1860, Bd. ii. For further
details regarding the influence of nerves on the composition of saliva, see article on
'' Mechanism of Salivary Secretion."

- Eckhard, loc. cit. ; Oehl, Jahresh. il. d. Fortschr. d. ge-i. Med., Erlangen, 1865, Bd. i.
S. 120. See also Brunton in Sanderson's "Handbook of the Physiol. Laboratory," p. 467.

^ See Astaschewsky, Jahresh. ii. d. Fortschr. d. Thier-Chem., Wiesbaden, 1878, Bd. viii.
S. 234; Fubini, ibid., S. 235.

"* Lehmann, "Physiol. Chem.," Bd. ii. S. 13.

^ Heidenhain, Arch. f. d. ges. Physiol., Bonn, 1878, Bd. xvii. S. 28 ; also in Hermann's
"Handbuch," Bd. v. (1), S. 55.


quantitative analysis, but made out that it was a clear slimy fluid of
stronger alkaline reaction than submaxillary saliva, and containing
mucin, diastatic ferment, and sulphocyanide.

The subungual saliva of the dog is a viscous, scarcely fluid mass ; it contains
salivary corpuscles, but is otherwise quite clear and transparent, is alkaline in
reaction, and contains 2"75 per cent, of total solids.^ Werther- has analysed
the sublingual saliva of the dog, and finds that its great viscidity is not due
to any excess of organic constituents ; he attributes it to the reaction which he
found to be neutral or barely alkaline. The proportion of inorganic salts is
much larger than in parotid or submaxillary saliva.

Secretion of the mucous glands of the mouth. — This has not
been obtained in man. In the dog it has been obtained by ligaturing
the ducts of all the salivary glands, or by extirpating the salivary
glands. The amount secreted is exceedingly small ; it is a thick ropy
mucus of alkaline reaction, full of fragments of epithelial and mucous
cells, and containing about 1 per cent, of total solids.^

The mixed sahva.— Mixed saliva may easily be obtained from the
mouth by depressing the head and everting the lower lip; or by
depressing the head, keeping the mouth widely open, and avoiding
all attempts to swallow. It is a clear, viscid, and very slightly
opalescent fluid, which froths easily. It is normally alkaline in
reaction; when it is acid this reaction is commonly due to fer-
mentation of particles of food in the mouth. The alkalinity is least
when fasting, as in the morning before breakfast, and reaches its
maximum with the height of secretion during, or immediately after
eating. According to Chittenden and Ely,^ the alkalinity is equiva-
lent to that of a solution containing 0'08 per cent, of sodium carbonate

The quantitative composition of mixed saliva is very variable, as
might be expected from the difference in composition of the secretions
which form it, and the varying proportion in which these must be pre-
sent in different samples. The amount of total solids in human saliva
varies normally between 5 and 10 parts per 1000 ; the specific gravity
between 1-002 and 1-008.

Organic constituents. — The organic matter is partially in suspension,
and partially in solution. The suspended matter consists of squamous
cells detached from the epithelium of the mouth, and of the sali-
vary corjniscles, which are leucocytes altered by the action of the
saliva, and containing granules which exhibit in fresh saliva active
Brownian movements. The dissolved organic matter consists of
mucin, ptyalin, and traces of proteids ; the amount of the latter is
so small that it cannot be quantitatively estimated. Saliva is also
said to contain normally minute traces of urea; but the amount
is so small that such a statement cannot be made with certainty.
In pathological conditions the amount of urea present may, however,
become very appreciable. Leucine and lactic acid are found under

^ Heideiihain, SfAicl. d. 'physiol. Inst, zu Breslau, Leipzig, Heft 4.

^ Arch. f. d. ges. Physiol., Bonn, 1886, Bd. xxxviii. S. 293. See also Langley and
Fletcher, Phil. Trans., London, 1887, vol. clxxx. p. 109.

^ Bidder and Schmidt, "Die Yerdauungssiifte," Mitau nnd Leipzig, 1852, S. 5.

^ Am. Chem. Journ., Baltimore, 1883, p. 329. See also Werther, Aj-ch. f. d. ges. Physiol.,
Bonn, 1886, Bd. xxxviii. S. 293.


pathological conditions, l)ut are not normal constituents. Grape-sugar
and bile pigments are never found even in the severest cases of diabetes
or icterus.^

Inorganic constituents. — These consist of salts of the alkalies (chiefly
sodium) and alkaline earths ; principally as chlorides, but also as
phosphates and carbonates.^ Calcium carbonate often separates from
saliva, as a thin surface film, or as a cloudiness in the fluid on standing ;
this is due to the escape of carbon-dioxide by which the calcium was
held in solution as bicarbonate. A precipitation of the calcium of the
saliva, partially as carbonate and partially as phosphate, in the ducts of
the salivary glands, often gives rise to salivary concretions ; and a similar
deposit, mixed with phosphate and traces of silica, forms the tartar
of teeth.

SuliJhocyanate of saliva. — Treviranus,^ as early as 1814, observed
that when a dilute solution of ferric chloride is added to saliva a reddish
coloration is obtained. This was even before sulphocyanic acid was
known chemically, and Tiedemann and GmeKn ^ afterwards proved that
the effect was due to the presence of a sulphocyanate.

The amount of sulphocyanate is not large. Oehl states it as equivalent to
0-00016-0"0084 per cent., estimated as potassium sulphocyanate, and Munk
as equivalent to O'Ol per cent, sulphocyanic acid, or 0'014 per cent, of
sodium sulphocyanate.'^ The presence of a sulphocyanate in saliva may be
demonstrated qualitatively in several ways — (1) A very greatly diluted and
slightly acidulated solution of ferric chloride is added drop by drop to saliva,
when a reddish coloration is obtained, if sulphocyanate is present in normal

Online LibraryE. A. (Edward Albert) Sharpey-SchäferText-book of physiology; (Volume v.1) → online text (page 48 of 147)