life and onward. Except the congenital example mentioned below, the
earliest age at which the disease has occurred, so far as I am able to
ascertain, is four years--a case reported by Wettergreen[51] of
hypertrophic sclerosis, in which neither a syphilitic nor paludal cause
could be ascertained. Cayley[52] reports a case in a child of six;
Murchison,[53] Frerichs,[54] Griffith,[55] one each at ten. After this
period the increase relatively to age is rapid. The majority of cases
occur between thirty {991} and fifty years. Yet Virchow[56] has given
the details of a congenital example. According to Förster, of 31 cases
of cirrhosis, 16 were between forty and sixty years. The preponderance
of cases in the male sex is very decided. Of Bamberger's 51 cases, 39
were men, 12 were women; of Frerichs' 36 cases, 20 occurred in men and
16 in women--a larger proportion of women than any other author
records; of 12 cases observed by myself, only 1 was a woman.
Nationality does not affect the production of cirrhosis, except as
regards the personal habits of the people. This disease is
comparatively uncommon in wine- and beer-drinking countries, and
frequent amongst a spirit-drinking people.[57] The great etiological
factor is the abuse, the habitual use, of spirits, and hence the number
of cases observed in North Germany, England, Scotland, and the United
States. Murchison affirms that he has never seen a case produced in any
other way. Even in children of tender years the abuse of spirits can
usually be traced. Nevertheless, there are instances of the disease the
origin of which cannot be referred to alcoholic excess. The congenital
cases, as that narrated by Virchow, and the instances occurring in
children and adults not given to spirits in any form, indicate that
there are other pathogenetic influences which may bring about a
sclerosis of the liver. Virchow[58] was one of the first to illuminate
the subject of visceral syphilis and to demonstrate the occurrence of
sclerosis of the liver from syphilitic infection. Very often the
syphilitic cachexia coincides with alcoholic excess. There can be no
doubt that chronic malarial poisoning causes, or powerfully predisposes
to, cirrhosis. I have submitted elsewhere pathological evidence on this
point,[59] and the Italian physicians, who have the opportunity to
obtain accurate data, maintain that malarial toxæmia does bring about
this state. It is probable that the overgrowth of connective tissue is
induced by the repeated congestions of the malarial attacks, and by the
obstruction due to catarrh of the bile-ducts which so often occurs in
the febrile paroxysms.
[Footnote 51: _Hygeia_, 1880, quoted by _London Medical Record_, March
15, 1881.]
[Footnote 52: _Transactions of the Path. Society of London_, vol.
xxvii., 1876, pp. 186, 194.]
[Footnote 53: _Clinical Lectures_, _loc. cit._]
[Footnote 54: _Clinical Treatise, etc._, Syd. Soc. ed., by Murchison.]
[Footnote 55: _Clinical Lectures_, _loc. cit._]
[Footnote 56: _Archiv f. path. Anat._, Band xxii. p. 426.]
[Footnote 57: Baer, _Der Alcoholismus_, Berlin, 1878, p. 62 _et seq._]
[Footnote 58: _Virchow's Archiv_, vol. xv. p. 281; also, Lancereaux, _A
Treatise on Syphilis_, Syd. Soc. ed.]
[Footnote 59: _Memoirs of the Sanitary Commission_, medical volume.]
J. Wickham Legg[60] and Charcot[61] nearly simultaneously discovered
that obstruction of the bile-ducts, if continued a sufficient length of
time, sets up a hyperplasia of the connective tissue of the liver. The
evidence is pathological and experimental. Thus, Legg has seen a liver
markedly cirrhotic in a case where a small cancer of the duodenum
completely obstructed the flow of bile into the intestine.[62] By tying
the common duct in dogs it was found that a hyperplasia of the
connective tissue very soon occurred, and this was followed, of course,
by contraction of the new tissue and atrophy of the hepatic cells.
Closure of the hepatic vein has the same effect, and also, as
Solowieff[63] has asserted, closure of the portal vein; on the other
hand, by Frerichs and others the closure of the portal is attributed to
the sclerosis.
[Footnote 60: _On the Bile, Jaundice, etc._, _loc. cit._, p. 351 _et
seq._]
[Footnote 61: _Leçons sur les Maladies du Foie, etc._, p. 231 _et
seq._]
[Footnote 62: _On the Bile, Jaundice, etc._, _loc. cit._, p. 355.]
[Footnote 63: _Arch. f. path. Anat., etc._, Band lxii. p. 195.]
Certain poisons, as antimony, arsenic, notably phosphorus, have the
power to set up an irritative hyperplasia of the connective tissue of
the {992} liver. These metals accumulate in the liver in preparation
for excretion. Wegner,[64] in the study of the action of phosphorus on
dogs, rabbits, and other animals, has induced a marked degree of
sclerosis, but such results have not been observed in cases of
poisoning by phosphorus in man, except in an instance reported by
Küssner.
[Footnote 64: _Virchow's Archiv_, Band lv. p. 18.]
Finally, a condition of the liver corresponding in all respects to
cirrhosis has been induced by perihepatitis, by the organization of the
exudation and its subsequent contraction, and by the extension of the
morbid process from the capsule to the interlobular connective tissue
(Poulin[65]).
[Footnote 65: _Étude sur les Atrophies viscérales consécutives aux
Inflammations chroniques du Sereuses, etc._, Thèse de Paris, 1880.]
PATHOLOGICAL ANATOMY.--Several forms of cirrhosis are recognized by the
modern French school of pathologists. According to Sabourin,[66] there
is an annular, a monolobular, and a multilobular form. These differ
merely in regard to the arrangement of the new connective tissue. At
the outset of the disease the liver is increased in size and hyperæmic.
Its consistence is also greater than normal. The outer surface is at
this period smooth, but on section the islets of the parenchymatous
tissue, yellowish in color, are distinctly visible between the grayish
or pale-rose tint of the intervening or proliferating tissue. This
reddish-gray material consists of fine connective-tissue elements
containing spindle-shaped cells.[67] The development of this material
is such as to even exceed in quantity the proper glandular structure.
The bands of newly-formed connective tissue extend between individual
lobules (monolobular cirrhosis) or between groups of lobules
(multilobular cirrhosis). A portion of the spindle-shaped cells form
new vessels communicating with the branches of the hepatic artery.[68]
Coincidently with the formation of the new connective tissue ensues its
contraction. The enlarged organ diminishes in size from a slight degree
to one-half its original volume; especially in the left lobe is the
diminution of size most marked. On the surface it exhibits a knobbed or
nodular aspect (hobnail liver), and these knobs present through the
capsule a yellow appearance. The granulations, so called, consist of
small prominences corresponding to lobules or groups of lobules, and
hence vary in size from that of a pinhead to that of a pea.[69] Between
these are the sharply-defined masses of connective tissue. On section
the organ is found to be of firm almost cartilaginous hardness, and
between the interlacing bundles of connective tissue are the small
islands of parenchymatous tissue projecting above the cut surface and
having a yellowish or brownish-yellow color. As the terminal branches
of the portal are compressed in the process of shrinking undergone by
the new connective tissue, they are destroyed. The result of this
obliteration of the portal radicles is the impaired nutrition of the
lobules and atrophy of the cells. Formerly it was held that the atrophy
of the hepatic cells was due to the compression exercised by the
contracting connective tissue, and Beale[70] even maintained that the
change began in {993} the cells, the connective tissue contracting as
the cells receded before them. This view has been reaffirmed by
Ackermann in a paper read last year before the Congress of German
Naturalists and Physicians, but without any acknowledgment, so far as I
can ascertain, of Beale's long-before expressed opinions. In the
discussion which followed the reading of Ackermann's paper the position
of its author was supported by Aufrecht, Küssner, and others, but
controverted by Rindfleisch. It has been demonstrated by Cohnheim and
Litten[71] that the lobule is nourished not only by the portal
radicles, but by the branches of the hepatic artery, which enter, by
the interlobular vein, the capillaries of the lobule, and hence the
nutrition of the cells suffers in consequence of the lessened
blood-supply; but it is probable also that more or less compression is
exercised. When the cells are destroyed, their remains may be discerned
in the mass of connective tissue as fine fat-granules or masses of
pigment yellowish or brownish in color. The peculiar appearance to
which the name cirrhosis is applied is due to the lobules or groups of
lobules which project on section above the divided surface, and are
colored yellowish by the bile-pigment, which here exists in an
exaggerated quantity. The cells themselves are not normal: they are
enlarged by compensatory hypertrophy, and they contain much
bile-pigment and a considerable quantity of fat. The compression of the
capillaries, especially their obliteration, leads to stasis of the
blood and its consequences in the whole chylopoietic system.
[Footnote 66: Ch. Sabourin, "Du Rôle que joue le Système veineux
sus-hépatique dans la topog. de la cirrhose du foie," _Revue de
Médecine_, June, 1882.]
[Footnote 67: Förster, _Lehrbuch der pathologischen Anatomie_, Jena,
1873, p. 264.]
[Footnote 68: Cornil, "Note sur l'État anatomique des Canaux biliaires
et des Vaisseaux sanguins dans la cirrhose du foie," _Gaz. méd. de
Paris_, 1883.]
[Footnote 69: Charcot, _Leçons sur les Maladies du Foie, etc._, p.
226.]
[Footnote 70: _Archives of Medicine_, vol. ii. p. 82.]
[Footnote 71: _Archiv für path. Anat._ (Virchow), Band lxvii. p. 153
_et seq._]
SYMPTOMS.--The development of sclerosis is usually very insidious.
After some years' indulgence in spirit-drinking or affected for a
length of time with the other causes of the malady, a gradual decline
of vigor occurs. The complexion takes on a fawn color, stigmata slowly
form on the face, there is more or less yellowness of the conjunctiva,
and attacks of headache, giddiness, and even severe vertigo, are
experienced. An increasing indisposition to mental effort, some
hebetude of mind, and a gradually deepening despondency are felt. The
appetite gradually fails, becomes capricious, and only highly-seasoned,
rather odd, or unusual articles of food can be taken. Such subjects
acquire a taste for condiments, for such uncooked vegetables as onions,
celery, raw cabbage, etc., for fruits, and get a distaste for
plainly-cooked meats and vegetables, for sweets, etc. The digestion is
as capricious as the appetite: at first there are times of appetite,
again of indifference, then of disgust; some heaviness is felt after
meals; gaseous eructations, acidity, pyrosis, nausea, occur day after
day as the case advances; and ultimately morning vomiting is regularly
experienced. Nausea is felt on rising; then with much straining and
distress a little glairy mucus and a teaspoonful of bile are brought
up; after which, it may be, a little food can be taken. It is only
after the case is fully declared that these troubles of stomach
digestion become constant; previously they occur now and then in a
paroxysmal way, whilst between there is only labored digestion.
As the compression of the portal radicles maintains, by reason of the
obstruction, a constant hyperæmia of the intestinal mucous membrane, a
catarrhal state, with fermentation of the fatty, starchy, and
saccharine constituents of the food, and hence complicated products of
an irritating kind, must result therefrom. Hemorrhoids, varying in size
according to {994} the degree of obstruction, form, sometimes bleeding
more or less profusely, again being merely troublesome or painful.
Fissures of the anus and fistula in ano not unfrequently complicate the
case. The bowels are necessarily rather relaxed than confined, but at
the onset of the malady they may be confined, afterward assuming more
or less of the characteristics of diarrhoea. The stools may be
offensive with the products of decomposition, rather clay-colored or
golden, or brownish and almost black from the presence of blood. In
some cases the stools are parti-colored--clay-colored in part, brownish
in part--and in exceptional examples continue normal or nearly so until
near the end. As the transudations from the portal vessels increase,
the mucous membrane of the intestinal canal becomes oedematous, and,
the normal secretions being arrested, the discharges finally consist of
a watery fluid, whitish or grayish, dark-brown or blackish, and very
offensive. The decomposition of foods instead of their proper digestion
and solution, and especially the fermentation of the starchy and
saccharine constituents of the aliment taken, produce a great quantity
of gas; hence meteorism comes to be an ordinary symptom. The
accumulation of gas is greatly promoted by the paretic state of the
muscular layer and by the relaxation of the abdominal walls consequent
on the oedema of the muscular tissue. A high degree of distress is
sometimes caused by the great accumulation of flatus; the abdomen is
greatly distended and the diaphragm is pushed up against the heart and
lungs, compelling the patient at length to sit up to breathe with ease.
Of course the accumulation of fluid may be greater, and the gas only
add to the discomfort.
A very common symptom is hemorrhage. Sometimes it happens, indeed, that
this is the only evidence of the portal obstruction at first observed.
Hæmatemesis is more common than intestinal hemorrhage. Now the blood
may be large in quantity, appear little changed from its usual
coagulated state, and be brought up promptly with slight effort of
vomiting; now it is passed by stool, is in coffee-colored, granular
masses or in a tar-like, semifluid state; and again it appears in
coffee-grounds mixed with the contents of the stomach. These variations
are due to the character, seat, and extent of the hemorrhage and to the
condition of the mucous membrane. Merely-distended capillaries,
yielding, may furnish a little blood, which, acted on by the gastric
juice, forms coffee-grounds, or, if not acted on in consequence of the
failure of the gastric glands to functionate, appears as bloody streaks
mixed with mucus. Enlarged veins, giving way, may furnish a large
quantity of partly-coagulated venous blood, charred or not as the state
of the juices will determine. In some cases hemorrhages into the
submucous tissue or thromboses of the submucous veins lead to solution
of the membrane thus deprived of its nutritional supply, and ulcers
form. Two admirable examples of this kind have been seen by the writer
in which large hæmatemesis occurred from ulcers near the pylorus. They
were round, smooth ulcers, containing coagula, and the eroded vessels
(veins) were readily seen opening into the cavity of each.
The obstruction to the portal circulation results also in an
enlargement of the spleen. There may be a simple enlargement due to the
hyperæmia merely; there may be an enlargement due to the hyperæmia and
to a resulting hyperplasia of the connective tissue; there may be also,
in {995} addition to the second form of enlargement, amyloid
degeneration, syphilitic hyperplasia, etc. The increased dimensions of
the spleen are by no means always made out, and authorities differ
greatly as to the proportion of cases in which the enlargement can be
detected. The organ may indeed be considerably enlarged whilst pushed
upward into the left hypochondrium by the effusion, and yet the attempt
to measure and define its dimensions may be fruitless. From a slight
increase due to the hyperæmia up to the enormous dimensions acquired by
the added amyloid material there are all possible variations in size.
Partly in consequence of the increased blood-pressure in the vessels of
the peritoneum, and partly in consequence of the watery condition of
the blood itself, effusion takes place into the sac of the peritoneum.
Such an accumulation is known as ascites, or dropsy of the abdomen. The
time at which the effusion begins, the amount of it, and the degree of
contraction of the liver necessary to produce it, vary in each case.
Ascites may be the first symptom to announce the onset of cirrhosis; it
is more frequently amongst the later symptoms, and is the evidence of
much interference in the portal circulation. However, it is not due
wholly to hepatic disease. The blood in cirrhosis is much reduced and
watery, hence slight causes suffice to induce an outward diffusion.
Given a certain obstacle to the passage of the blood through the liver,
transudation will be the more prompt to appear the greater the anæmia.
In some cases an enormous quantity of fluid collects: from ten to
thirty pounds may be regarded as usual, and forty to sixty pounds as
exceptional, although the highest amount just given is not rare. The
fluid of ascites nearly represents the serum of the blood. It has a
straw color and is clear, but it may have a reddish tint from the
presence of blood, a greenish-yellow or brown from bile-pigment. The
solids of the serum are in the proportion of from 1 to 3 per cent., and
consist of albumen chiefly and salts, of which sodium chloride is the
principal. Hoppe's[72] analysis gives this result: 1.55 to 1.75 solids,
of which 0.62 to 0.77 is albumen. According to Frerichs, the amounts of
solids ranges from 2.04 to 2.48, and of these albumen constitutes 1.01
to 1.34.
[Footnote 72: _Virchow's Archiv für path. Anat., etc._, Band ix.]
Oedema of the inferior extremities comes on after, usually--rarely
with--the ascites. If the mechanism of this oedematous swelling be as
supposed, the effusion into the areolar tissue necessarily succeeds to
the abdominal effusion. The pressure of the fluid in the cavity on the
ascending vena cava and iliac veins seems to be the principal factor;
but to this must also be added the intestinal gas, which in some
instances exerts a powerful force. The ankles have in rather rare cases
appeared swollen before the abdomen, but the detection of fluid in the
peritoneal cavity when in small quantity is not always easy. Obese
women, with much accumulation of fat in the omentum and flatus in the
intestines, have swollen feet and legs if erect for some time, the
effusion being due to pressure on the vena cava. The legs may become
enormously distended. The scrotum and penis in the male, the vulva in
the female, the buttocks and the abdominal wall, also become
oedematous, sometimes immensely. Walking grows increasingly difficult.
Warmth and moisture and the friction of the sensitive surfaces excite
vesicular and pustular eruptions where the {996} scrotum and labiæ come
in contact with the thighs. Urination may be impeded by the oedema of
the prepuce.
An attempt at compensation for these evils growing out of the
obstruction in the portal system is made by the natural powers.
Anastomoses of veins through minute branches are made use of to convey
the blood of the obstructed portal circulation into the general venous
system, and to this end become greatly enlarged. The interlobular veins
being obliterated by the contracting connective tissue, the pressure in
the branches and trunk of the portal vein is much increased. Hence an
outlet is sought for in the veins which communicate between the portal
and the ascending vena cava. One of the most important of these is a
vein in the round ligament, at one time supposed to be the closed
umbilical vein, but proved by Sappey to be an accessory portal vein.
Bamberger,[73] however, has found the umbilical vein pervious, and
since, Hoffmann[74] has demonstrated the same fact. It is probable,
indeed, that Sappey's observation is correct for some cases. In either
event, the veins of the abdominal wall about the umbilicus
communicating with the epigastric become enormously distended, and in
some advanced cases of cirrhosis form a circle known as the caput
Medusæ. Further communication between the portal and the veins of the
diaphragm takes place by means of the veins in the coronary and
suspensory ligaments. In some instances a new route is established
between the veins of the diaphragm and the portal by means of new
vessels formed in the organized connective tissue resulting from
perihepatitis. Still another channel of communication exists between
the inferior oesophageal veins, the azygos, and the coronary, and
finally between the inferior hemorrhoidal and the hypogastric. The more
completely can communication be established between these anastomosing
veins the less severe the results of portal obstruction.
[Footnote 73: _Krankheiten des Chylopoiet. Syst._, _loc. cit._]
[Footnote 74: Quoted by Thierfelder, _op. cit._]
Besides these indirect evidences of portal obstruction and a
contracting organ, there are direct means of ascertaining the condition
of the liver. By the methods of physical diagnosis we may acquire much
information. On auscultation, as our Jackson[75] was the first to show,
a grating or creaking like leather, or friction sound, is audible over
the right hypochondrium synchronously with the respiratory movements or
when produced by moving with the fingers the abdominal wall on the
liver. This sound is caused by the bands of false membrane which extend
between the two surfaces, and hence indicates a secondary
perihepatitis.
[Footnote 75: _The American Journal of the Medical Sciences_, July,
1850.]
To ascertain the dimensions of the liver--to mark out the area of
hepatic dulness--with accuracy is a most necessary procedure. The
period of the disease is an important element in the problem. When the
new material is deposited and the congestion of the portal system first
occurs, an increase in the dimensions of the organ is observed. This
enlargement, of brief duration, must not be confounded with the
hypertrophic sclerosis, another form of the malady. So considerable is
the increase in the size of the liver that there is an evident
enlargement of the right hypochondrium, and the whole abdomen seems
fuller. The organ may be felt, on palpation, projecting one, two, or
even three fingers' breadths below the margin of the ribs, and the left
lobe extends well across the epigastrium, increasing the sense of
resistance and the area {997} of dulness in this direction. The
enlarged liver, as felt below the ribs, appears firmer than is natural,
is yet smooth, and the margin is sharply defined. The duration of this
period of enlargement is indefinite, but it is rather brief, and is
followed by the contracting and atrophic stage. It is not often,
indeed, that the patient presents himself during the period of
enlargement. Sometimes a perihepatitis or an unwonted tenderness in the
right side compels attention during this stage, but more frequently it
escapes notice. If perihepatitis occur, there will be fever, pain, and
tenderness, a slight icterode hue of the skin, and possibly
Jackson's[76] friction sound. These symptoms, taken in conjunction with
the history of the case and the obvious enlargement of the organ, will
indicate the existence of the first stage of sclerosis.
[Footnote 76: _The American Journal of the Medical Sciences_, July,
1850, _supra_.]