It contains:
(1.) Mucus, which gives bile its sticky character, and not unfre-
quently makes it alkaline, is the product of the mucous glands and the
goblet-cells of the mucous membrane of the larger bile-ducts. When
bile is exposed to the air, the mucus causes it to putrefy rapidly. It is
precipitated by acetic acid, or alcohol. [Bile from the gall-bladder,
when poured from one vessel into another, shows the presence of mucin
in the form of thin threads connecting the fluids in the two vessels.
When such bile is treated with alcohol, it no longer exhibits this
property, but flows like a non-viscid watery fluid. The bile formed in
the ultimate bile-ducts does not seem to contain mucin or mucus, but
bile from the gall-bladder always does.]
(2.) The Bile Acids. Glycocholic and taurocholic acids, so-called
conjugate acids, are united with soda (in traces with potash) to form
glycocholate and taurocholate of soda, which have a bitter taste. In
human bile (as well as in that of birds, many mammals, and amphibians),
taurocholic acid is most abundant; in other animals (pig, ox) glyco-
cholic acid is most abundant. These acids rotate the plane of polarised
light to the right.
(a.) Glycocholic acid, C^H^NOg (first discovered and described as
cholic acid by Gmelin, and called, by Lehmann, glycocholic acid).
When boiled with caustic potash, or baryta water, or with dilute
mineral acids, it takes up H 2 O (Strecker, 1848), and splits into
Glycin ( = Glycocoll = Gelatin Sugar =Amidoacetic acid) =C 2 H 5 N0 2 .
+ Cholalic acid (also called Cholic acid) . . .
= Glycocholic acid + Water ". '. = C 26 H43N0 6 + H 2 O.
(b.) Taurocholic acid, C 26 H 45 NS0 7 , when similarly treated, takes
up water and splits into
Taurin (= Amidosethyl-sulphuric acid)=C 2 H 7 NSO 3 .
+ Cholalic acid ....
= Taurocholic acid + Water . . = C 26 H45NS0 7 + H 2 (Strecker).
Preparation Of the Bile acids. Bile is evaporated to of its volume, rubbed
up into a paste with excess of animal charcoal, and dried at 100C. The black
mass is extracted with absolute alcohol, which is filtered until it is clear. After a
part of the alcohol has been removed by distillation, the bile salts are precipitated
in a resinous form, and on the addition of excess of ether, there is formed immedi-
ately a crystalline mass of glancing needles (Planner's "crystallised bile"). The
alkaline salts of the bile acids are freely soluble in water or alcohol, and insoluble in
ether. Neutral lead acetate precipitates the glycocholic acid as lead glycocholate
from the solution of both salts ; the precipitate is collected on a filter, dissolved
in hot alcohol, and the lead is precipitated as lead sulphide by H 2 S ; after removal
of the lead sulphide, the addition of water precipitates the isolated glycocholic
acid. If, after precipitating the lead glycocholate, the filtrate be treated with
356, THE BILE ACIDS.
basic lead acetate, a precipitate of lead taurocholate is formed, from which the
acid may be obtained in the same way as described above (Strecker).
When human bile is similarly treated, instead of the "crystallised bile," a
resinous non -crystalline precipitate is obtained. Boiling with baryta water isolates
the cholalic acid from it, which is obtained from its barium salt by adding hydro-
chloric acid. When dissolved in ether, it occurs in the form of prismatic crystals
if petroleum-ether is added. The anthropocholic acid (C 18 H 28 4 H. Bayer), so
obtained is not soluble in water, but readily so in alcohol, and rotates the ray of
polarised light to the left.
With regard to the decomposition products of the bile acids,
as such, does not occur in the body, but only in the bile in combination
with cholalic acid, in urine in combination with benzoic acid, as
hippuric acid, and lastly, in gelatin in complex combination.
Cholalic acid rotates the ray of polarised light to the right, and its
chemical composition is unknown (perhaps it is to be regarded as
benzoic acid, in which a complex of atoms similar to oleic acid is intro-
duced Hoppe-Seyler). It occurs free only in the intestine, where it is
derived from the splitting up of taurocholic acid, and it passes in part
into the faeces. It is insoluble in water, soluble in alcohol, but soluble
with difficulty in ether, from which it separates in prisms. Its
crystalline alkaline salts are readily soluble in water.
Cholalic acid is replaced in the bile of many animals by a nearly related acid,
e.g., in pig's bile, by hyo-cholalic acid (Strecker, Gundlach); in the bile of the
goose, cheno-cholalic acid is present (Marsson, Otto).
When cholalic acid is boiled with concentrated HC1, or dried at
200C, it becomes an anhydride, thus:
Cholalic acid . = C 2 4H 40 5 , produces
Choloidinic acid = C 2 4H 38 04 + H 2 0, and this again yields
Dyslysin . . = C 2 4H 36 3 = H 2 0.
(Choloidinic acid is, however, not improbably a mixture of cholalic acid and
dyslysin ; dyslysin, when fused with caustic potash, is changed into cholalate
of potash Hoppe-Seyler). If anthropocholic acid be heated to 185C, it gives up
1 molecule of water, and yields anthropochol-dyslysin (Bayer).
By oxidation cholalic acid yields a tribasic acid, as yet uninvestigated, and a
fair amount of oxalic acid, but no fatty acids (Cleve).
Pettenkofer's Test. The bile acids, cholalic acids, and their anhy-
drides, when dissolved in water, yield on the addition of f concentrated
sulphuric acid (added in drops so as not to heat the fluid above 70C),
and several drops of a 10 p. c. solution of cane-sugar, a reddish purple
transparent fluid, which shows two absorption-bands at E & F (Schenk).
[A very good method is to mix a few drops of the cane-sugar solu-
tion with the bile, and to shake the mixture until a copious froth is
obtained. Pour the sulphuric acid down the side of the test-tube, and
then the characteristic colour is seen in the froth.]
According to Drechsel, it is better to add phosphoric acid, instead of sulphuric
THE BILE PIGMENTS. 357
acid, until the fluid is syrupy, then add the cane-sugar, and afterwards place the
whole in boiling water. When investigating the amount of bile acids in a liquid,
the albumin must be removed beforehand, as it gives a reaction similar to the
bile acids, but in that case the red fluid has only one absorption-band. If only
small quantities of bile acids are present, the fluid must in the first place be
concentrated by evaporation.
The origin of the bile acids takes place within the liver. After its
extirpation, there is no accumulation of biliary matters in the blood
(Joh. Miiller, Kunde, Moleschott).
How the formation of the nitrogenous bile acids is effected is quite unknown.
They must be obtained from the decomposition of albuminous materials, and it is
important to note that the amount of bile acids is increased by albuminous food.
Taurin contains the sulphur of albumin ; bile salts contains 4- 4 '6 p.c. of sulphur
(Voit), which may perhaps be derived from the stroma of the dissolved red blood -
corpuscles.
(3.) The Bile Pigments. The freshly secreted bile of man and many
animals has a yellowish-brown colour, due to the presence of bilirubin
(Stadler). When it remains for a considerable time in the gall-bladder,
or when alkaline bile is exposed to the air, the bilirubin absorbs and
becomes changed into a green pigment, biliverdin. This substance is
present naturally, and is the chief pigment in the bile of herbivora
and cold-blooded animals.
(a.) Bilirubin (C 32 H 36 N 4 6 ) is, according to Stadler and Maly,
perhaps united with an alkali; it crystallises in transparent fox-red
clinorhombic prisms. It is insoluble in water, soluble in chloroform, by
which substance it may be separated from biliverdin, which is in-
soluble in chloroform. It unites as a monobasic acid with alkalies, and
as such is soluble. It is identical with Virchow's haematoidin
(p. 35).
Preparation. It is most easily prepared from the red (bilirubin-chalk) gall-
stones of man or the ox. The stones are pounded, and their chalk dissolved
by hydrochloric acid ; the pigment is then extracted with chloroform.
That bilirubin is derived from haemoglobin is very probable, considering its
identity with hsematoidin. Very probably red blood-corpuscles are dissolved in
the liver, and their haemoglobin changed into bilirubin.
(6.) Biliverdin (Heintz), C 32 H 36 N 4 8 , is simply an oxidised derivative
of the former, from which it can be obtained by various oxidation
processes. It is readily soluble in alcohol, very slightly so in ether,
and not at all soluble in chloroform. It occurs in considerable
amount in the placenta of the bitch. As yet it has not been retrans-
formed by reducing agents into bilirubin.
Tests for Bile Pigments. Bilirubin and biliverdin may occur in
other fluids e.g., the urine, and are detected by the Gmelin-Heintz'
reaction. When nitric acid containing some nitrous acid is added to the
liquid containing these pigments, a play of colours is obtained, begin-
ning with green (biliverdin), blue, violet, red, ending with yellow.
358
CHOLESTERIN.
[This reaction is best done by placing a drop of the liquid on a white
porcelain plate, and adding a drop of the impure nitric acid.]
(c.) If when the blue colour is reached, the oxidation process is arrested, bili-
Cyanin (Heynsius, Campbell), in acid solution blue, (in alkaline violet) is obtained,
which shows two ill-defined absorption-bands near D (Jaffd). Capranica advises
that the acid fluids be shaken with a mixture of chloroform and alcohol (1:1).
This mixture absorbs the pigment ; pour off the fluid and add bromine in alcohol
(| p.c.), and the play of colour is obtained.
(d.) BiliftlSCin occurs in small amount in decomposing bile and in gall-stones
=bilirubin+H 2 O.
(e.) Biliprasin (Stadler) also occurs = bilirubin + H 2 O + O.
(/.) The yellow pigment, which results from the prolonged action
of the oxidising reagent, is the choletelin (C 16 H 18 N 2 O 6 ) of Maly ; it is
amorphous, and soluble in water, alcohol, acids, and alkalies.
(g.) Hydro-bilirubin. Bilirubin absorbs H + H 2 (by putrefaction,
or by the treatment of alkaline watery solutions with the powerfully
reducing sodium amalgam), and becomes converted into Maly's hydro-
bilirubin (C 32 H 14 N 4 O r ), which is slightly soluble in water, and more
easily soluble in solutions of salts, or alkalies, alcohol, ether, chloroform,
and shows an absorption-band at &, F. This substance, which, accord-
ing to Hammarsten, occurs in normal bile, is a constant colouring-
matter of faeces, and was called stercobilin by Vaulair and Masius, but
is identical with hydro-bilirubin (Maly). It is, however, probably
identical with the urinary pigment urobilin of Jaffe" (Stokvis, p. 35).
(4.) Cholesterin, C^H^O (H 2 0) is an alcohol which rotates the
ray of polarised light to the
left, and whose constitution is
unknown; it occurs also in
blood, yelk, nervous matter, and
[gall-stones]. It forms trans-
parent rhombic plates, which
usually have a small oblong
piece cut out of one corner
(Fig. 145, a). It is insoluble in
water, soluble in hot alcohol, in
ether, and chloroform. It is
kept in solution in the bile by
the bile salts.
Preparation. It is most easily
prepared from so-called white gall-
stones, which not unfrequently con-
sist almost entirely of cholesterin, by
extracting them with hot alcohol after
they are pulverised. Crystals are
excreted after evaporation of the
alcohol, and they give a red colour
Fig. 145.
Crystals of Cholesterin a, regularly
laminated; b, irregularly laminated,
partially injured forms; x 300 (Aitken
after Wedl).
THE SECRETION OF BILE. 359
with sulphuric acid (5 vol. to 1 vol. H 2 Moleschott), while they give a blue
as cellulose does with sulphuric acid and iodine. When dissolved in chloro-
form, 1 drop of concentrated sulphuric acid causes a deep red colour (H. Schiff).
(5.) Amongst the other organic constituents of bile are: Lecithin
(p. 36), or its decomposition product, neurin (cholin), and glycero-
phosphoric acid (into which lecithin may be artificially transformed by
boiling with baryta); Palmitin, Stearin, Olein, as well as their soda
soaps Diastatic Ferment (Jacobson, v. Wittich) ; traces of Urea
(Picard) ; (in ox bile, acetic acid and propionic acid, united with
glycerine and metals, Dogiel).
[The proportion of diastatic ferment is not greater than in the tissues of the
body generally (M. Hay).]
(6.) Inorganic constituents of bile (0'6 to 1 p.c.):
They are sodium chloride, potassium chloride, calcic and magnesic phosphate,
and much iron, which in fresh bile gives the ordinary reactions for iron, so that
iron must occur in one of its oxidised compounds in bile (Kunkel); manganese and
silica. Freshly secreted bile contains in the dog more than 50 vol., and in the
rabbit 109 vol. per cent. C0 2 (Pfltiger, Boguljubow, Charles), partly united to
alkalies, partly absorbed, the latter, however, being almost completely absorbed
within the gall-bladder.
Thejnean composition of human bile is :
0-5 p.c.
. , 1-3
0-61 .
Farther, unchanged fat probably always passes into the bile, but is
again absorbed therefrom (Virchow). The amount of S in dry dog's
bile = 2'8-3'l p.c., the N = 7-10 p.c. (Spiro); the sulphur of the bile is
not oxidised into sulphuric acid, but it appears as a sulphur-compound
in the urine (Kunkel, v. Voit).
178. Secretion of Bile.
The secretion of bile is not a mere filtration of substances already
existing in the blood of the liver, but it is a chemical production of the
characteristic biliary constituents, accompanied by oxidation, within the
hepatic cells, to which the blood of the gland only supplies the raw
material. The liver-cells themselves undergo histological changes
during the process of digestion (Heidenhain, Kayser). It is secreted
continually; it is partly stored up in the gall-bladder, and is poured
out copiously during digestion.
The higher temperature of the blood of the hepatic vein, as well
as the large amount of C0 2 in the bile (Pfliiger), indicate that
oxidations occur within the liver. The water of the bile is not merely
Water, .
82-90 p.c.
Lecithin,
Bile Salts, .
6-11
Mucin,
Fats and Soaps,
9
* ?>
Ash,
Cholesterin, .
0-4
360 CONDITIONS INFLUENCING THE SECRETION OF BILE.
filtered through the blood-capillaries, as the pressure within the bile-
ducts may exceed that in the portal vein.
(2.) The quantity of bile was estimated by v. Wittich from a biliary
fistula, at 533 cubic centimetres in 24 hours (some bile passed into the
intestine); by Westphalen, at 453-566 grms.; [by Murchison, at 40
oz.]; Joh. Eanke, on a biliary-pulmonary fistula, at 652 cubic centi-
metres. The last observation gives 14 grms. (with 0'44 grms. solids)
per kilo, of man in 24 hours.
Analogous values for animals are 1 kilo, dog, 32 grm. (1'2 solids) Kolliker,
H. Muller; 1 kilo, rabbit, 137 grm. (2'5 solids) Bidder and Schmidt; 1 kilo,
guinea-pig, 176 grms. (5 '2 solids) Bidder and Schmidt.
(3.) The excretion of bile into the intestine shows two maxima
during one period of digestion; the first, from 3 to 5 hours, and the
second, from 13 to 15 hours after food. The cause is due to simul-
taneous reflex excitement of the hepatic blood-vessels, which become
greatly dilated.
(4.) The influence of food is very marked. The largest amount is
secreted after a flesh diet, with some fat added ; less after vegetable
food; a very small amount with a pure fat diet; it stops during
hunger. Draughts of water increase the amount, with a correspond-
ing relative diminution of the solid constituents.
(5.) The influence of blood supply is variable :
(or.) Secretion is greatly favoured by a copious and rapid blood supply. The
blood-pressure is not the prime factor, as ligature of the cava above the diaphragm,
whereby the greatest blood-pressure occurs in the liver, arrests the secretion
(Heidenhain).
(&.) Simultaneous ligature of the hepatic artery (diameter 54 mm.) and the
portal vein (diameter 6 mm.) abolishes the secretion (Rohrig). These two vessels
supply the raw material for the secretion of bile.
(c.) If the hepatic artery be ligatured, the portal vein alone supports the
secretion (Simon, Schiff, Schmulewitsch, Asp). According to Kotfcmeier, Betz,
Cohnheim and Litten, ligature of the artery or one of its branches ultimately
causes necrosis of the parts supplied by that branch, and eventually of the entire
liver, as this artery is the nutrient vessel of the liver.
(d.) If the branch of the portal vein to one lobe be ligatured, there is only a
slight secretion in that lobe, so that the bile must be formed from the arterial
blood (Schmulewitsch and Asp). Complete ligature of the portal vein rapidly
causes death. [The blood-pressure falls rapidly and the blood accumulates in the
blood-vessels of the abdomen. In fact, the accumulation of the blood within the
abdomen takes place to so great an extent, that practically the animal is bled
into its own abdomen (p. 176).]
Neither the ligature of the hepatic artery by itself (Schiff, Betz), nor the
gradual obliteration of the portal vein by itself, causes the cessation of the
secretion, but it is diminished. That sudden ligature of the portal vein causes
cessation is explained by the fact, that in addition to diminution of the secretion,
the enormous stagnation of blood in the rootlets of the portal vein in the abdominal
organs makes the liver very anaemic, and thus prevents it from secreting.
(e.) If the blood of the hepatic artery is allowed to pass into the portal vein
(which has, been ligatured on the peripheral side), secretion continues (Schiff).
BILIARY FISTULA. 361
(/.) Profuse loss of blood arrests the secretion of bile, before the muscular and
nervous apparatus become paralysed. A more copious supply of blood to other
organs e.g. , to the muscles of the trunk during vigorous exercise, diminishes the
secretion, while the transfusion of large quantities of blood increases it (Landois);
but if too high a pressure is caused in the portal vein, by introducing blood from
the carotid of another animal, it is diminished (Heidenhain).
({/.) The influence Of nerves. All conditions which cause contraction of the
abdominal blood-vessels e.g., stimulation of the ansa Vieussenii, of the inferior
cervical ganglion, of the hepatic nerves (Afanassiew) of the splanchnics, of the
spinal cord (either directly by strychnia, or reflexly through stimulation of sensory
nerves) affect the secretion; and so do all conditions which cause stagnation or
congestion of the blood in the hepatic vessels (section of the splanchnic nerves,
diabetic puncture, 175), section of the cervical spinal cord (Heidenhain). Par-
alysis (ligature) of the hepatic nerves causes at first an increase of the biliary
secretion (Afanassieff).
(h.) With regard to the raw material supplied to the liver by its blood-vessels,
it is important to note the difference in the composition of the blood of the hepatic
and portal veins. The blood of the hepatic vein contains more sugar (?), lecithin,
cholesterin (Drosdoff), and blood-corpuscles, but less albumin, fibrin, haemoglobin,
fat, water, and salts.
(6.) The formation of bile is largely dependent upon the decomposi-
tion of coloured blood-corpuscles, as they supply the material necessary
for the formation of some of its constituents.
Hence, all conditions which cause solution of the coloured blood- corpuscles are
accompanied by an increased formation of bile ( 180).
(7.) Of course a normal condition of the hepatic cells is required for
a normal secretion of bile.
Biliary Fistulae. The mechanism of the biliary secretion is studied in animals
by means of biliary fistulee. Schwann opened the belly by a vertical incision a.
little to the right of the ensiform process, cut into the fundus of the gall-bladder,
and sewed its margins to the edges of the wound in the abdomen, and afterwards
introduced a cannula into the wound. As a rule all the bile is discharged externally;
but to be quite certain that this is so, the common bile-duct ought to be tied between
two ligatures, and divided. After a fistula is freshly made the secretion falls.
This depends upon the removal of the bile from the body. If bile be supplied the
secretion is increased. Regeneration of the divided bile-duct may occur in dogs.
v. Wittieh observed a biliary fistula in man. [A temporary biliary fistula may also
be made. The abdomen is opened in the same way as described above. A long
bent glass cannula is introduced and tied into the common bile-duct, and the cystic
duct is ligatured or clamped. The tube is brought out through the wound in the
abdomen. Necessarily all the bile must be discharged by the tube].
179. Excretion of Bile,
[In connection with the excretion of bile, we must keep in view two
distinct mechanisms. (1) The bile-secreting mechanism dependent upon
the liver-cells, which are always in a greater or less degree of activity;
(2) the bile-expelling mechanism, which is specially active at certain
periods of digestion (p. 360).]
362 EXCRETION OF BILE.
This occurs (1.) Owing to the continual pressure of the newly-
formed bile within the interlobular bile-ducts forcing onward the bile
in the excretory ducts.
(2.) Owing to the interrupted periodic compression of the liver from
above, by the diaphragm, at every inspiration. Farther, every inspira-
tion assists the flow of blood in the hepatic veins, and every respiratory
increase of pressure within the abdomen favours the current in the
portal vein.
It is probable that the diminution of the secretion of bile, which occurs after
bilateral division of the vagi, is to be explained in this way; stilt it is to be
remembered, that the vagus sends branches to the hepatic plexus. It is not decided
whether the biliary excretion is diminished after section of the phrenic nerves and
paralysis of the abdominal muscles.
(3.) Owing to the contraction of the smooth muscles of the larger bile-
ducts and the gall-bladder. Stimulation of the spinal cord, from which
the motor nerves for these structures pass, causes acceleration of the
outflow, which is afterwards followed by a diminished outflow (Heiden-
hain, J. Munk). Under normal conditions, this stimulation seems to
occur reflexly, and is caused by the passage of the ingesta into the
duodenum, which, at the same time, excites movement of this part of
the intestine.
(4.) Direct stimulation of the liver (Pfliiger), and reflex stimulation
of the spinal cord (Rohrig), diminish the excretion ; while extirpation
of the hepatic plexus (Pfliiger), and injury to the floor of the fourth
ventricle (Heidenhain) do not exert any disturbing influence.
(5.) A relatively small amount of resistance causes bile to stagnate
in the bile-ducts.
A manometer, tied into the gall-bladder of a guinea-pig, supports a column of
200 millimetres of water; and secretion can take place under this pressure
(Heidenhain, Friedlander, Barisch). If this pressure be increased, or too long
sustained, the watery bile passes from the liver into the blood, even to the amount
of four times the weight of the liver, thus causing solution of the red blood-
corpuscles by the absorbed bile ; and very soon thereafter, haemoglobin appears in
the urine.
180. Reabsorption of Bile.
Phenomena of Jaundice (Icterus; Cholaemia).
Absorption Jaundice. When an impediment or resistance is offered to the
outflow of bile into the intestine e.g., by a plug of mucus, or a gall-stone
which occludes the bile-duct, or where a tumour or pressure from without, makes it
impervious the bile-ducts become filled with bile and cause an enlargement of the
liver. The pressure within the bile-ducts is increased. As soon as the pressure
has reached a certain amount, which it soon does when the bile-duct is occluded
(in the dog 275 mm. of a column of bile Afanassiew) reabsorption of bile from
the distended larger bile-ducts takes place into the lymphatics (not the blood-
PHENOMENA OF JAUNDICE. 363
vessels) of the liver (Saunders, 1795); the bile acids pass into the lymphatics of the
liver. [The lymphatics can be seen at the portal fissure filled with a deep yellow-
coloured lymph]. The lymph passes into the thoracic duct, and so into the blood
(Fleischl, Kunkel, Kufferath). Even when the pressure is very low within the
portal vein, bile may pass into the blood, without any obstruction to the bile-duct
being present. This is the case in Icterus neonatorum, as after ligature of the
umbilical cord, no more blood passes through the umbilical vein; farther, in the