form and a more or less well-defined crystalline structure. The forms
taken are various. The most usual form is octagonal or hexagonal or
polyangular, with smooth facets, corresponding to points of contact of
other calculi. Instead of smooth facets and sharp angles, the
concretion may be studded with irregularly-shaped masses. When there
are numerous {1059} calculi present, they have smooth surfaces and
rather sharp angles, made, not by attrition, as has been supposed, but
by deposition of the new material under pressure. When they have this
form there are many present, but the number of facets does not indicate
the number of calculi, and the absence of facets is not proof of the
absence of other calculi. The smooth opposing surfaces are not always
plane, but may be convex or concave to fit the shape of the adjacent
bodies.
Calculi may be globular, ovoid, cylindrical, and truncated cones. The
largest in my collection is egg-shaped, and nearly filled the
gall-bladder which contained it, a little mucus free from bile-elements
only being present. If a concretion forms in a duct or a single one is
present in the gall-bladder, the shape is determined by the pressure of
the walls of the duct or of the gall-bladder, respectively. As found in
the stools, and still somewhat soft, the shape will represent the form
of the common duct through which it has been pressed. Such a soft,
recently-formed gall-stone will have the crystalline structure and
chemical constitution of these bodies, and will therefore differ from,
apparently, similar masses of inspissated bile. Although a round,
ovoid, or cylindrical calculus indicates the absence of others because
there are no evidences of mutual pressure and adaptation, a positive
conclusion cannot be reached in that way, for the gall-bladder may
contain numerous calculi of long-standing, and a recent concretion
formed in a duct be discharged with the usual symptoms.
The number of calculi which may be present at any time or be produced
in the course of years ranges from one to several thousand. The number
is in inverse ratio to the size. One case[154] is reported in which
7802 calculi were found in the gall-bladder, but they must have been
very minute in size. Of the specimens now in my collection, there are
230 obtained from one gall-bladder, which they entirely filled; they
are nearly uniform in size, have an average weight of two grains, and
contain four, five, and six smooth facets. Another collection of
calculi removed from a closed gall-bladder contains 45, of large size,
distending the organ and forming a tumor which projected beyond the
margin of the liver. Hepatic calculi are rarely solitary; hence if one
attack of hepatic colic occur, others may be expected.
[Footnote 154: Frerichs, _op. cit._, vol. ii. p. 499.]
In color gall-stones vary from a clear white to a dark-brown, almost
black, tint. The most usual tint of the mature calculi in the
gall-bladder is that of the ripe chestnut. Long stay in the intestines
increases the depth of the color, until it becomes almost black; on the
other hand, detention in the gall-bladder has a slightly bleaching
action; but the real cause of difference of color is the presence or
absence of pigment. If composed of pure cholesterin, the color will be
whitish, opaque, or glistening and almost translucent.
In size gall-stones vary from the smallest pea up to a hen's egg. When
several hundreds are contained in the gall-bladder, they will usually
be of the dimension of a medium-sized pea. Two large solitary
concretions in my possession are respectively 2 inches and 1½ inches in
long diameter, and 1 inch and ¾ of an inch transversely. Very much
larger calculi have, however, been recorded; thus, one mentioned by
Frerichs is 5 inches in length and 4 inches in circumference. The most
frequently {1060} encountered calculus, at least in this country, is
polyangular in shape and of the size of a large pea. Globular or ovoid
seems to be the prevailing form, and the dimensions that of a small
pea, in Germany, according to Frerichs and Von Schüppel, but this
statement must refer to the initial shape of these bodies.
Not all hepatic calculi have defined mathematical forms, but may
consist of branching cylinders composed of irregular nodular masses,
not unlike the concretions of inspissated bile. As a rule, in each case
where the calculi are multiple there is uniformity of color, shape, and
composition. This feature is well exhibited in my collection. The
calculi obtained from each subject are in one case white, polyangular,
rather unctuous, and nearly equal in size; in another, chestnut-brown
in color, polyangular in shape, and varying slightly in size, but
uniformly characteristic in shape; and in a third, singular in number,
ovoid in shape, dark-brown in color.
In composition gall-stones vary somewhat. When fresh they contain
considerable water, and at all times are hygroscopic. Dried in the air,
they are composed of--
Water 4
Solids 96
---
100
The solids consist of--
Cholesterin 98
Pigment 1
Inorganic or mineral matter 1
---
100
Such are the constituents, according to Harley, of the usual
concretion, the cholesterin calculus. But as other varieties are
encountered occasionally, it may be well to give the composition of
these. The following table by Ritter, to be found in _Robin's Journal_
for 1872 (p. 60), is a correct representation of the contents of
different specimens:
---------------+------+------+------+------+------+------+------+-----
Composition | | | | | | | |
of Different | | | | | | | |
Kinds. | 1st. | 2d. | 3d. | 4th. | 5th. | 6th. | 7th. | 8th.
---------------+------+------+------+------+------+------+------+-----
Cholesterin | 98.1 | 97.4 | 70.6 | 64.2 | 81.4 | 84.3 |trace.| 0
Organic | | | | | | | |
matter | 1.5 | 2.1 | 22.9 | 27.4 | 15.4 | 12.4 | 75.2 | 18.1
Inorganic | | | | | | | |
matter | 0.4 | 0.5 | 6.5 | 8.4 | 3.2 | 3.3 | 24.8 | 91.9
Number of | | | | | | | |
specimens | 28 | 16 | 580 | 94 | 220 | 16 | 3 | 1
---------------+------+------+------+------+------+------+------+-----
The above may be regarded as the average composition, expressed in
round numbers. The variations from these figures will be comprehended
in two parts.
A calculus consists of three several parts: the nucleus, the body, the
rind. A calculus of small or medium size may be a nucleus for the
formation of a large one. Usually the nucleus consists of a bit of
mucus, casts of the biliary ducts (Thudicum), inspissated bile, a
blood-clot, a liver-fluke or other parasite, as a desiccated
round-worm, or some foreign body, as a seed, or, as in one reported
example, a globule of mercury.[155] {1061} The central mass of mucus
may contain a large proportion of pigment or crystals of cholesterin or
lime-salts, giving it special characteristics.[156] There may be
several nuclei. Fauconneau-Dufresne reports an instance in which a
pyramidal concretion contained four, and Guilbert a globular stone with
five, distinct nuclei. Such examples of calculi having multiple nuclei
are produced by the adhesion whilst in a soft state of two or more, and
the subsequent addition of material to the conjoint mass, welding it
into a single stone. A few calculi are homogeneous throughout, composed
of nearly pure cholesterin, mixed intimately with a little coloring
matter and lime salts. The cholesterin calculus will have a somewhat
translucent appearance, will be a dead white or a yellowish-white, or
present a greenish- or brownish-yellow tint through the white. Even the
white calculus, apparently composed of nearly pure cholesterin, will be
found on section to contain traces of a nucleus. By long detention in a
gall-bladder whose duct is permanently occluded, and is therefore free
of fluid, the mucus nucleus may so shrivel as to leave a cavity which
is merely stained. One of my specimens--a solitary calculus of large
size--exhibits this peculiarity.
[Footnote 155: Thudicum, J. L., _On Gall-stones_, London, 1863; also
Frerichs, _op. cit._, vol. ii. p. 503.]
[Footnote 156: Cyr, Jules, _Traité de l'Affection calculeuse du Foie_,
Paris, 1884, p. 11 _et seq._]
The body consists of cholesterin, nacreous or darkened by pigment,
deposited in radiating lines or in concentric layers, or in both
together. Pigment may be intimately incorporated with the cholesterin
or deposited between the layers of this substance, pure or nearly pure,
forming an alternating arrangement.
The crust or rind usually is smooth, unctuous to the touch, firm, but
when broken with the finger-nail readily crumbles. When composed of
lime salts, or when the cholesterin is mixed with varying proportions
of these salts and of pigment, the surface is still smooth, but
thicker, firmer, and darker in color. The rind may not be smooth, but
studded with wart-like projections, or it may consist of several layers
of earthy matter separated by pigment. These layers may be very
friable, and readily crumble and fall off. In some instances the crust,
several lines in thickness, is the body of the calculus, and the cavity
contains only a light honeycomb of mucus and pigment.
The specific gravity of gall-stones composed of crystallized
cholesterin is nearly that of water. Air-dried calculi will float on
water, but the recent ones, full of moisture, sink. The relation of the
weight of the calculus to that of the bile is more important. As the
specific gravity of bile ranges from 1020 to 1026, it is obvious that
on this fluid air-dried calculi will float, but, holding in the recent
state much water, ordinary gall-stones will sink. Those containing much
mineral matter will have a correspondingly high specific gravity--much
higher than bile.
ORIGIN AND FORMATION OF HEPATIC CALCULI.--Certain conditions are
necessary to the formation of these bodies on the part of the bile and
on the part of the gall-bladder and ducts. Constituted for the most
part of cholesterin, which exists in such small quantity in normal
bile, there must be some change in the composition of this fluid to
increase the quantity or to diminish the solubility of that
constituent. It will conduce to a better understanding of the subject
to premise the composition of the bile: {1062}
Bile contains, in 1000 parts,
Water 860
Solids 140
The solids of bile are,
Glycocholate and Taurocholate of soda 90.8
Fat 9.2
Cholesterin 2.6
Mucus 1.4
Pigment and extractive 28.
Salts 8.
-----
140.
Normal bile is neutral or slightly alkaline in reaction. If the
reaction become acid from any cause, the constituent cholesterin is
precipitated; and this occurs the more readily the larger the
proportion of this substance held in solution. Cholesterin is an
excrementitious material found in the blood and excreted by the liver.
It represents in part, probably, the waste of nervous matter, but more
certainly of the fatty tissues in general. Conditions of the system in
which the metamorphosis of the fatty elements occurs more freely--as
obesity, advancing life, etc.--are accompanied by an increased
production and excretion of cholesterin.
So long as the neutral state or the alkalinity of the bile is
maintained, the cholesterin will be kept in solution, although its
relative proportion may be in excess of the normal. A lack of the soda
constituent of the system is one factor, but the most important is a
catarrhal state of the mucous membrane of the bile-ducts and
gall-bladder. The mucus formed plays a double rôle: it furnishes a
nucleus about which cholesterin crystallizes; it acts as a ferment and
inaugurates a process of acid fermentation which results in the
precipitation of cholesterin. When all the conditions favorable to the
separation and crystallization of cholesterin are present, any foreign
body may serve the purpose of a nucleus. The articles which have thus
served have been enumerated.
A by no means infrequent combination is that of bilirubin with calcium;
and this may constitute the nucleus or form a part of the body or the
crust of a calculus. The mechanism of its formation is not unlike that
of the cholesterin concretion. Bilirubin is soluble in alkalies, and is
precipitated from its solution by acids. It follows that when acid
fermentation takes places under the influence of mucus, bilirubin may
be precipitated in combination with calcium. The salts of sodium and
potassium are much more abundant in bile than those of lime, but the
latter much more often enter into the formation of calculi because of
their slighter solubility. Other combinations of bile-pigments, mucus,
and the salts of the bile take place, but they are relatively less
frequent. The principal lime salt is the carbonate, and this combines
in varying proportions with the bile acids, the fat acids, and
bile-pigment.
Certain physical conditions are not less important than the chemical in
the production of hepatic calculi. Accumulation of bile in the
gall-bladder, stasis, and concentration are essential conditions. If
bile remains long in the gall-bladder, it becomes darker in color and
more viscid, its specific gravity rises, and the relative proportion of
solids increases, doubtless because of the absorption of a part of the
water. The reaction--which, as has been stated, is in the fresh state
neutral or {1063} alkaline--becomes acid in consequence of a
fermentative change (Von Gorup-Besanez) set up by the mucus. If a
catarrhal state of the mucous membrane exist, the mucus, epithelium,
and lymphoid cells cast off play the part of a ferment. The lime which
is so important a constituent of biliary concretions is not present
even in concentrated bile in sufficient amount to account for its
agency in the formation of these bodies, is furnished by the diseased
mucous membrane (Frerichs). Indeed, numerous crystals of carbonate of
lime have been seen in situ in contact with the mucous membrane in
cases of chronic catarrh. It follows, then, that catarrh of the biliary
passages has an important causative relation to that pathological
condition of the bile which precedes the formation of calculi. In this
connection we must not lose sight of the researches made by Ord[157] on
the action exerted by colloids on the formation of concretions. The
mucus is the colloid; cholesterin, lime, and soda salts are the
crystalloids. These latter diffusing through the colloid medium, the
resulting combinations assume spheroidal forms. The union of bilirubin
and lime salts illustrates the same principle.
[Footnote 157: _On the Influence of Colloids upon Crystalline Forms and
Cohesion, with Observations on the Structure and Mode of Formation of
Urinary and other Calculi_, by W. Miller Ord, M.D., F.R.C.P. Lond.,
etc., London, 1879.]
CAUSES.--We have here to consider the external conditions and the
general somatic influences which lead to the formation of biliary
concretions. Age has an important causative action. Besides other
agencies due to advancing life, the increase of cholesterin is an
influential factor. The less active state of the functions in general,
diminished oxidation, loss of water, and concentration of the bile are
influential factors in determining the formation of hepatic calculi in
advancing life, as the opposite conditions oppose their production in
early life. Although not unknown in infancy, at this period in life and
until twenty years of age they occur but rarely.
Fauconneau-Dufresne,[158] of 91 cases, had 4 in infants; Wolff[159] had
1 in a collection of 45 cases; and Cyr,[160] 2 cases under ten in a
group of 558 cases. The following table illustrates the influence of
age on the productivity of gall-stones:
AUTHORS.
HEIN.
Whole No. 395
From infancy to 30 18
From 30-70 377
FAUCONNEAU-DUFRESNE.
Whole No. 91
Before 20 10
From 20-40 13
From 40-90 68
WOLFF.
Whole No. 45
Before 20 3
From 30-60 42
DURAND-FARDEL.
Whole No. 230
Before 20 2
From 20-30 28
From 30-60 162
From 60-90 38
CYR.
Whole No. 558
Before 20 20
From 21-30 208
From 31-40 185
From 41-50 91
From 51-60 48
Above 60 6
[Footnote 158: _Traité de l'Affection calculeuse du Foie_, Paris,
1851.]
[Footnote 159: _Virchow's Archiv f. path. Anat., etc._, Band xx., 1861,
p. 1.]
[Footnote 160: _Traité de l'Affection calculeuse du Foie_, Paris, 1884,
p. 53.]
Although there is a general correspondence in the results of the
observations on the age most liable, there are differences. Thus, Cyr,
whose figures represent the experiences at Vichy, makes the age of
maximum liability from twenty to forty years--distinctly earlier than
any other observer; and hence it is necessary to bear in mind the
extreme latitude of his diagnosis. Of my own collection, 30 in number,
all doubtful cases {1064} excluded, there were 20 between thirty and
fifty years, and 10 between fifty and seventy. Of these, 22 occurred in
subjects between forty and sixty. The period of maximum liability is
about fifty years of age. Cyr refers the difference of his statistics
from those of other observers to the character of the patients. The
preponderance in the number of cases of hepatic calculi at or about the
fiftieth year is referable to the lessened activity of the nutritive
functions at this period, and to the increase in the relative
proportion of cholesterin in the blood in advanced life (Luton[161]).
Charcot[162] maintains that after sixty biliary calculi are more
frequent, but owing to the physiological conditions then existing the
migration of these bodies is effected without notable inconvenience.
[Footnote 161: Jaccoud's _Dictionnaire encyclopéd._, art. "Voies
Biliaires;" _idem._, _Bull. gén. de Thérap._, March 15, 1866.]
[Footnote 162: _Leçons sur les Maladies du Foie, etc._, p. 145.]
According to most authorities, females are more liable to the formation
of gall-stones than are men. Thudicum, after an analysis of the
statistics given by the most experienced and celebrated authorities,
places the proportion at 3 to 2. Von Schüppel gives the same figures.
Cyr, whilst recognizing this estimate as true of the great mass of
observations on this point, finds that in his own cases the
preponderance of females over males was even greater, being 4 to
1--inversely to the liability of the sexes to gout; but this excess is
to be explained by the character of the subjects falling under his
observation. Women are subjected to influences which favor the
formation of these concretions, such as pregnancy, sedentary habits,
diet of a restricted character, the use of corsets, and the somatic
changes at the climacteric period.
The social state, by reason of the conditions associated with a good
position in life, has an influence in the production of calculi.
Luxurious habits and indulgence in the pleasures of the table are
important factors, and hence this malady is encountered amongst the
better class of patients in private practice rather than amongst
laboring people in the hospitals.
As the somatic conditions which exert a predisposing action, and the
social circumstances also favoring the formation of hepatic calculi,
are transmitted, heredity is by some classed among the etiological
factors, but it can only be regarded as indirect.
Malarial influences unquestionably exert a very powerful influence as
this malady occurs in this country. Paroxysms of intermittent either
induce or accompany the seizures of hepatic colic, and chronic malarial
poisoning exerts a direct causative influence through the hepatic
disturbances and the gastro-duodenal catarrh which are associated with
it. Attacks of hepatic colic are extremely frequent in the malarial
regions of the West and South. It may be, however, that this malady is
frequent rather in consequence of the diet of pork than of climatic
causes, for it is probable that indulgence in such food plays an
important part in the formation of biliary concretions (Harley). Due
allowance made for diet, climate is yet, no doubt, an influential
factor. In warm, especially in malarial, regions the functions of the
liver are taxed to compensate for the increased action of the skin and
lungs; but this organ is, besides, affected by the poison of malaria,
and to the congestion caused by it is superadded a catarrhal state of
the bile-ducts and of the duodenum. A {1065} pathological condition of
the bile itself is first induced; then the fermentative changes set up
by the mucus cause the separation and crystallization of pigment and
cholesterin.
Certain seasons favor the formation of biliary concretions, because
then the special influences which operate at all times are more active
and persistent. These seasons are fall, winter, and early spring, and
gall-stones are more numerous then in consequence of the activity of
the malarial poison, the character of the diet then employed, and the
lessened oxidation due to the more sedentary life. Climate is a factor
of some consequence, but not in the direction that might have been
supposed. Gall-stones are more common in temperate than in tropical
climates--a statement confirmed by the observation of the physicians of
India. They are, according to Harley, quite common in Russia, where
also they attain to extraordinary dimensions; but these circumstances
are not due to the climatic peculiarities of that country, so much as
to the diet habitually consumed, consisting so largely of fatty
substances.
Of all the conditions which favor the production of gall-stones, none
are so influential as the bodily state and the associated dietetic
peculiarities. Those troubled with these concretions, as they have
occurred under my observation, have been either obese or have had a
manifest tendency in that direction. They have had a strong inclination
for the fat-forming foods, also for starchy, saccharine, and fatty
articles, such as bread and butter, potatoes, beans and peas, pork,
bacon, and fat poultry, etc. Harley thinks indulgence in bacon (p. 367)
is a prime factor. Thudicum rejects this notion on chemical grounds,
for obesity and the free consumption of fat cannot be concerned in the
production of these bodies, because cholesterin is an alcohol.[163] The
agency of a fatty diet has been so strongly indicated in clinical
observations, and the relation of cholesterin to the fats so obvious,
that it can hardly be doubted the free consumption of fat in food
contributes directly to the formation of calculi. An indirect relation
may also be traced. A catarrhal state of the duodenal mucous membrane
existing, and the bile excluded by swelling and obstruction of the
bile-ducts, fats are decomposed, and the fat acids, absorbed into the
portal blood, contribute to those chemical changes in the bile which
result in the precipitation of cholesterin. Beneke[164] traces a
connection between atheromatous degeneration of the vessels and the
formation of biliary concretions. A general increase in the amount of
fat in the body is usually coincident with the atheromatous change, and
at the same time the relative proportion of cholesterin in the bile
becomes greater.
[Footnote 163: _A Treatise on Gall-stones_, p. 214.]
[Footnote 164: _Deut. Archiv für klin. Med._, Band xviii.]
Indulgence in the starchy and saccharine foods plays a part in the
formation of gall-stones not less, if not more, important than the
consumption of fats. A diet of such materials is highly fattening, and
if the necessary local conditions exist they readily undergo
fermentation, and thus cause or keep up a catarrh of the mucous
membrane.