Lebert's collection of 72 cases there were 44 men and 28 women, but it
is now known that he did not properly discriminate in his selection of
supposed examples of the disease. The statistics of all other observers
are opposed to those of Lebert. Thus, in Frerichs' collection of 31
cases, carefully sifted to eliminate error, there were 22 women and 9
men. Legg has also collected 100 cases of acute yellow atrophy, and of
these 69 were women or girls. The most active period of life--from
twenty to thirty years of age--is the usual period for the appearance
of this disease. More than one-half of Lebert's cases occurred between
fifteen and twenty-five; and of Frerichs', two-thirds happened between
twenty and thirty years of age. In Legg's collection of 100 cases, 76
were between fifteen and thirty-five years of age. What is the
condition of women at this period in life which renders them so
susceptible to this malady? There can be no doubt that pregnancy is the
great factor. Of 69 cases especially interrogated on this point,
examined into by Legg, in 25 pregnancy was ascertained to exist. In
Frerichs' collection one-half were women in the condition of pregnancy.
The period of pregnancy at which the disease appears varies from the
fourth to the ninth month, the greatest number occurring at the sixth
month. So long ago as 1848, Virchow drew attention to the remarkable
changes in the liver due to pregnancy. Sinety[126] has studied the
effect of lactation on the liver, and has ascertained the existence of
fatty degeneration. There is a form of jaundice which accompanies
menstruation, as shown by Senator,[127] Hirschberg, and others. These
facts indicate a certain relationship between the sexual system of the
female and the liver, but they do not indicate the nature of the
connection, if any exist, between this condition and acute yellow
atrophy.
[Footnote 126: _De l'État du Foie chez les Femelles en Lactation_,
Paris, 1873 (pamphlet).]
[Footnote 127: _Berliner klinische Wochenschrift_, 1872, p. 615, "Ueber
Menstruelle Gelbsucht."]
The influence of depressing emotions has been supposed to be effective
{1025} in producing this disease, but it is more than doubtful if such
a relationship exists. Lebert, however, refers 13 of his cases to this
cause, but Legg, who bases his statements on the study of 100
carefully-recorded cases, is sceptical regarding the effect of such
influences. Syphilis has in some instances appeared to be the
principal, if not the only, pathogenetic factor, and Legg[128] compares
the action of the virus of syphilis to the effect of phosphorus,
mercury, etc.
[Footnote 128: _On the Bile, Jaundice, and Bilious Diseases_, _loc.
cit._]
PATHOLOGICAL ANATOMY.--The anatomical changes occurring in this disease
indicate the existence of a systemic condition: the lesions are not
limited to the liver, but involve various other organs. The changes in
the liver should be first described, since the name of the disease is
derived from the alterations in this organ. As the name indicates, the
lesions are atrophic, but not all examples show this. In some cases
there is little change in the size of the organ; in others the wasting
is extreme; certainly in all typical examples the liver is reduced in
size. The variations in size observed are probably due to the stage at
which the inspection is made: if early, the organ may not be reduced in
size, may be even somewhat enlarged by the deposition of new material;
if later, the atrophic changes will be more or less pronounced. When
the atrophy has taken place, the size of the liver is reduced to
one-half, even to one-third, of its original dimensions; it is then
soft, almost like pulp, and cannot maintain its shape, but flattens out
on the table. The capsule is much wrinkled and the color of the organ
is yellowish, variegated by islets of reddish or brownish-red color,
these spots being somewhat depressed below the general surface and
having a firm texture. On section the boundaries of the lobules are
either lost or have become very indistinct, the line of section being
bloodless. The knife with which the sections are made becomes greasy.
In some instances ecchymoses are discovered under the capsule, and
rarely hemorrhagic extravasations in the substance of the liver. The
bile-ducts are found intact, as a rule. The greatest change in the size
of the liver is observed in the left lobe. The duration of the disease,
as has been indicated above, has a marked influence over the size and
condition of the liver. The atrophic shrinking of the liver occurs more
decidedly after the ninth day. In general, the tissue of the liver is
soft and pulpy in consistence. On microscopic examination the most
important alterations are seen to have occurred in the hepatic cells;
ultimately, these cells disappear, being replaced by fatty and
connective-tissue detritus; but before this stage is reached important
alterations have taken place in the form and structure of these bodies:
the cells become granular and fatty, and lose their sharpness and
regularity of contour, especially at the periphery of the lobule, but
ultimately all the cells within the lobule undergo atrophic
degeneration. In this atrophic degeneration of the hepatic cells, in
their fatty degeneration, and ultimately entire disappearance, consist
the real proofs of the disease. The red islets of tissue already
alluded to consist of the fatty detritus mixed with crystals of
hæmatoidin.
More or less increase of the connective tissue is noted in many of the
cases--increase of connective tissue with numerous young cells formed
around the vessels and the bile-ducts (Waldeyer[129]). The changes in
the {1026} liver would surely be incomplete without some references to
the minute organisms which play so important a part in modern
pathology. Waldeyer was the first to demonstrate the presence of
bacteria in the pigment-remains of the hepatic cells. Other observers
have been unable to detect them, so that at present the parasitic
origin of this affection remains sub judice.
[Footnote 129: _Arch. für path. Anat._, 1868, p. 536, Band xliii.]
Important changes also take place in the spleen, but the opinions on
this point are somewhat contradictory. Frerichs found the spleen
enlarged in most of his cases; Liebermeister, on the other hand, and
Legg,[130] find that the spleen is enlarged in about one-third of the
cases. When the atrophic changes occur in the liver, more or less
swelling of the splenic veins must occur in consequence of portal
obstruction. The peritoneum, especially the omental part, is the seat
of multiple ecchymoses, and the endothelium is fatty. The mesenteric
glands are usually swollen. More or less blackish or brownish fluid,
consisting of altered blood, is usually found in the stomach, and the
same, assuming a tar-like consistence, in the large intestine.
Ecchymoses of rather small size are distributed over the stomach and
intestines. The epithelium of the stomach-glands is found granular and
disintegrating, and a catarrhal state of the gastro-intestinal mucous
membrane exists throughout. The secretions are never normal, and the
stools are wanting in bile or present a tarry appearance, due to the
presence of blood.
[Footnote 130: _On the Bile, Jaundice, and Bilious Diseases_, _supra_.]
Important changes take place in the kidneys. They consist essentially
in a granular and fatty degeneration of the tubular epithelium, whence
the altered appearance of the cortex. Multitudes of bacteria crowd the
pyramids. Ecchymoses also are found in the mucous membrane of the
pelvis of the kidney, in the bladder, and indeed all along the
genito-urinary tract.
The muscular tissue of the heart is in a state of acute fatty
degeneration, beginning with a granular change which may at the outset
be of very limited extent and involve but few fibres. The endo- and
pericardium are studded with ecchymoses or marked by hemorrhagic
extravasations, and the pleura presents similar appearances, but not to
the same extent.
The brain does not always show evidences of change, but in many
instances there are ecchymoses of the meninges; the walls of the
vessels are affected by fatty degeneration.
The tissues of the body are more or less deeply stained with bile. The
pathological change on which the jaundice depends has been variously
stated, but the most probable explanation is that which refers it to
mechanical obstruction of the bile-ducts, either by catarrhal swelling
or fatty degeneration of the epithelium. Notwithstanding the prominence
of the hepatic symptoms, acute atrophy of the liver is probably only
one element in a constitutional morbid complexus.
SYMPTOMS.--Acute yellow atrophy begins in two modes--the grave symptoms
preceded by mild prodromes, or the most serious symptoms appear at the
onset. The former mode is the more common. The usual prodromes are
referable to the gastro-intestinal canal, and consist of loss of
appetite, nausea, vomiting, a bitter taste in the mouth, headache, and
general malaise. Indeed, the opening attack may be much like an {1027}
ordinary bilious seizure or acute gastro-duodenal catarrh or a sick
headache. In some cases the initial symptoms--nausea and
diarrhoea--appear to be induced by an indigestible article of food.
Jaundice never fails to be present at some period, but is usually one
of the prodromic symptoms. It has no special characteristics by which
the gravity of the approaching seizure may be measured. It is usually
rather deep, and all parts are deeply stained, but the coloration may
be limited to the body and upper extremities. No change in pulse or
temperature, except the usual depression of both functions, is to be
observed; the urine is deeply stained with pigment, and the feces are
grayish, colorless, or parti-colored.
The period of time elapsing before the serious symptoms come on is not
constant; from one week to several months have been the variations
observed. In a minority of the cases no prodromes have occurred, but
the grave symptoms have declared themselves at once. From the
appearance of the jaundice up to the onset of severe symptoms the time
has varied from two weeks to several months, but has rarely exceeded
three months. During this time there may be nothing to indicate the
gravity of the approaching symptoms; in fact, the case then, as at the
onset, seems to be one of simple gastro-duodenal catarrh associated
with catarrhal jaundice. The onset of serious symptoms is most usually
announced by dilatation of the pupil. If, therefore, in a case of
apparently simple catarrhal jaundice, especially in a pregnant female,
there should occur without apparent reason a marked and persistent
dilatation of the pupil, the possibility of the case being one of acute
atrophy should be apprehended. This symptom is not, alone, of
sufficient value to decide the character of the case, but then an
obstinate insomnia comes on, violent headache is experienced, there is
more or less confusion of mind, and jactitations or an extreme
restlessness occurs. When such pronounced nervous symptoms appear the
character of the attack is explained.
Various divisions have been proposed to mark the type of the symptoms:
thus, the icteric period embraces the prodromal symptoms with jaundice;
the toxæmic period is that stage characterized by profound nervous
disturbances. Ozonam has divided the symptoms into those of the
prodromal period and those of the serious stage, the latter being
subdivided into the symptoms of excitation and those of collapse. There
may be no prodromal period, however; without any preliminary symptoms
the patient is suddenly seized with delirium and passes into a
condition of coma and insensibility, or the first evidence of serious
illness may be convulsions. It is probable, however, that in even the
most sudden cases mild prodromal symptoms had occurred, but were
overlooked. There is much variability in the symptoms of the toxæmic
period. There are three symptoms: excitement with delirium, sometimes
delirium ferox; coma, less or more profound; and convulsions. Legg has
numerically expressed the relative frequency of these symptoms thus: Of
100 cases of unquestionable acute atrophy, 76 had become comatose, 59
were delirious, and 32 had suffered convulsions.[131] According to the
same authority, delirium and coma were associated together in about
one-half of the cases, but in pregnant women coma often occurs alone
(Legg). Usually, when convulsions happen there has been either coma or
delirium. With these cerebral symptoms there are often present various
{1028} disturbances of motility and sensibility, such as local
convulsions, jactitations, hiccough, extreme restlessness, paralysis of
the sphincters, and incontinence of urine and feces or retention,
grinding of the teeth, exalted sensibility of the skin, or it may be
complete anæsthesia, severe itching of the surface, etc.
[Footnote 131: _On the Bile, Jaundice, and Bilious Diseases_, _loc.
cit._]
During the toxæmic period, and directly dependent on the retention of
excrementitious matters in the blood, hemorrhages occur from the mucous
surfaces, from wounds, and into the various serous membranes. A changed
state of the blood being present in all cases of this disease, the
proportion in which extravasations take place is high--in about 71.3
per cent. according to Liebermeister, and 80 per cent. according to
Legg. The latter author regards these estimates as rather low. When
hemorrhage occurs in the stomach in small amount, it presents itself as
coffee-grounds or as black vomit, and in the intestine in the form of
black, tarry stools or melæna. Hemorrhage may also occur from the
surface of an ulcer, from a fresh wound, a leech-bite, etc.; but the
most usual form of extravasation of blood after the gastro-intestinal
is epistaxis or bleeding from the nose. Women who abort, as they are
very apt to do when this disease comes on, may suffer from frightful
hemorrhage, and deaths have been thus caused. Various opinions have
been expressed as to the cause of the hemorrhagic condition--by some
attributed to the changes in the composition of the blood; by others to
the alterations of the vessel walls; both factors are doubtless
concerned.
During the prodromic period the temperature of the body, as in the case
of ordinary uncomplicated jaundice, is rather depressed below normal,
sometimes as much as two degrees; but when the toxæmic stage comes on
the body-heat rises to a variable extent, but usually over 100° F. In
some cases no febrile movement can be detected; in others a very
considerable elevation of temperature occurs, but very rarely attains
to 105° or 106° F. The pulse becomes very rapid, in some instances
rising to 140; but without any apparent cause it may fall suddenly to
70 or 80, and these fluctuations may take place several times a day.
The rise of temperature and a very rapid pulse may come on in the final
coma only; and immediately after death, as Legg points out, the
body-heat may attain the maximum elevation.
As the toxæmic period develops the tongue becomes dry, glazed,
fissured, sordes form on the teeth and lips, the breath becomes fetid,
and the breathing may assume the Cheyne-Stokes type. The nausea and
vomiting of the prodromal period persist, and the ominous
coffee-grounds appear in the rejected matters, or grumous masses--clots
acted on by the gastric juice--are brought up. Black, pitch-like, or
tarry stools, the result of hemorrhage, are passed toward the
end--involuntarily when liquid. When no blood is present the stools are
grayish and without bile. Constipation may be the condition instead of
diarrhoea in about one-third of the cases.
Various eruptions have been observed on the skin, such as petechiæ,
roseola, eczema, etc., but their very variety, as their occasional
appearance, indicates their accidental relationship to the disease.
The urine is much altered in character, but it is usually acid in
reaction, although it has been observed neutral or alkaline. The
specific gravity is at or nearly normal, and it has a deep-brownish or
bilious hue {1029} due to the presence of bile-pigment. The most
important change in the composition of the urine is the diminished
quantity of urea or its entire disappearance; the phosphates, and
especially the chlorides, are also usually diminished in amount; and
albumen and leucin and tyrosin appear to a lesser or greater extent,
together with hyaline, fatty, and granular casts.
Although the observations are somewhat contradictory, it seems pretty
definitely established that the blood is more or less altered in
composition, morphological and chemical. The red corpuscles are
diminished in amount, and often deformed; the white corpuscles are
increased; and excrementitious products--urea, leucin, tyrosin, and
cholesterin--are found in greater or less quantity.
COURSE, DURATION, AND TERMINATION.--Although, as a rule, the course of
acute atrophy is rapid, it is not invariably so. In some instances the
prodromic symptoms have continued through several months, but,
according to Thierfelder, one-half of the cases terminate in from three
to five weeks, and in only 10 per cent. is the duration continued into
eight weeks. The course of the disease is extremely rapid in pregnant
females, rarely extending beyond the second week. An extended course of
the disease is due to delay in the prodromic stage, the toxæmic period
being always absolutely and relatively shorter. In the condition of
pregnancy the danger is increased by the hemorrhages, and the early
termination is due chiefly to this factor. When the duration of the
disease is protracted and its evolution normal, the accumulation of
hepatic excrementitious matters sets up cerebral disturbance, which
becomes a pronounced feature of the case.
The termination cannot probably be otherwise than fatal. As in the
course of the disease the hepatic cells undergo solution and
disintegration, their restoration can hardly be regarded as possible,
certainly not probable. Any curative result must, then, be wrought in
the prodromic period, when the diagnosis must be viewed with some
mistrust.
DIAGNOSIS.--George Harley[132] maintains the singular doctrine that
acute yellow atrophy is only the "sporadic form of the contagious
jaundice of the tropics," or yellow fever. He bases his opinion on the
identity of their symptoms, pathological anatomy, mortality, and
contagious character; for he affirms that acute yellow atrophy may
exhibit contagious power in temperate climates.
[Footnote 132: _Diseases of the Liver_, Amer. ed., 1882, p. 255.]
As acute yellow atrophy comes on as an ordinary catarrhal jaundice, it
is impossible to distinguish it from the latter affection during the
prodromal period. When cerebral symptoms, black vomit, and tarry stools
appear, the area of hepatic dulness very decidedly diminishes, and
leucin and tyrosin replace urea in the urine, acute atrophy may be
suspected.
Acute phosphorus-poisoning, as regards its symptomatology and morbid
anatomy, does not differ from acute yellow atrophy, and many cases of
the latter have been mistaken, it is supposed, for the former. To
distinguish between them the history of the case must be carefully
ascertained.
When, after the prodromal symptoms, which may not be accurately
diagnosticated, there occurs a rapid decline in the area of hepatic
dulness, hemorrhages take place from the mucous surfaces, stupor and
delirium {1030} supervene, and urea disappears from the urine, being
replaced by leucin and tyrosin, there can be no difficulty in coming to
a conclusion: the case must be one of acute yellow atrophy.
TREATMENT.--It was formerly supposed that a case of acute yellow
atrophy must necessarily prove fatal, but this opinion must now be
modified, since examples of cure of supposed cases have been reported
from Oppolzer's clinic,[133] by Lebert,[134] by Harley,[135] and
others. As at the onset the symptoms cannot be distinguished from a
bilious attack or from catarrhal jaundice, the treatment must be
appropriate to these states. When the serious symptoms begin, a large
dose (scruple j) of quinine should be at once administered, and half
the quantity at regular intervals to keep up the cinchonism. Phosphate
of soda, with some arseniate and such mild hepatic stimulants as
euonymin, iridin, etc., should be given to maintain a gentle aperient
action. Experience has proved that active or drastic cathartics do harm
rather than good; on the other hand, mild laxatives, especially those
having cholagogue action, seem to do good.
[Footnote 133: Thierfelder, _op. cit._]
[Footnote 134: _Ibid._]
[Footnote 135: _Diseases of the Liver_, Amer. ed., _supra_.]
Important symptoms arising during the toxæmic period require remedies
to combat them. Nausea and vomiting, and also diarrhoea, are best
relieved by carbolic acid and bismuth in combination. Hemorrhage
requires, when intestinal, the chloride and perchloride of iron; when
from other mucous surfaces, ergotin, gallic acid, and other
hæmostatics. The depression of the vital forces should be treated by
small and frequently-repeated doses of alcohol, by quinine, by iron,
and, under some conditions, by digitalis. After the disintegration of
the hepatic cells has been produced no remedies can be of any service.
Until this occurs, however, it seems to the author well worth while to
attempt to stay the destruction by the administration of those remedies
which, by their accumulation in that organ, indicate a special affinity
for its tissue. These drugs are phosphorus, antimony, gold, silver, and
mercuric chloride. By the timely administration of one or more of these
would it not be possible to stay the progress of the atrophic
degeneration?
The Liver in Phosphorus-Poisoning.
DEFINITION.--Poisoning by phosphorus may seem to be a toxicological
question rather than a merely hepatic disease, but as the morbid
complexus thus induced is so similar to acute yellow atrophy that the
conditions are regarded as identical by many of our German colleagues,
it is necessary to enter into some details regarding it.
PATHOGENY.--Phosphorus-poisoning occurs at any period from youth to old
age, but is most common from twenty to thirty years of age. Women seem
more inclined to effect self-destruction in this way than are men,
probably because phosphorus matches are so readily obtained. Children
may munch match-heads in a spirit of mischief. That form of chronic
poisoning seen in workmen in match-factories, and consisting in
necrosis of bone, etc., does not come within the scope of the present
inquiry.