completely obliterated, and the duct itself immensely distended with
dark thick tarry bile, which on microscopic examination, was found
loaded with beautiful crystals of cholesterine. (Fig. 7.)
[Illustration: FIG. 7.]
The gall-bladder was enlarged to the size of a swan's egg, and
contained thick tarry fluid; but no gall-stones, or masses of
inspissated bile. The hepatic duct was greatly enlarged, easily
admitting {83} the point of the finger. The cystic duct was also
dilated, though in a much less degree. (Vide Plate I., _c_. _d_. _e_.)
Thirdly,--The gall-bladder, duodenum, abdominal parietes, and in fact
all the abdominal viscera, were intensely stained, almost blackened, by
the osmosed bile.
Fourthly,--The bile, on analysis, was found to contain in one thousand
parts:--
Water . . . . 694·45
Solids . . . 305·55
------
1000·00
=======
Pigment . . . . |
Bile-acids . . | Organic matter . 288·99
Cholesterine . |
Soda . . . . . |
Potash . . . . | Inorganic salts . 16·56
Iron . . . . . |
Whereas a specimen of normal bile taken from the gall-bladder of a
woman aged sixty-one, was of a specific gravity of 1020, and contained
in 1000 parts:--
Water . . . . 933·27
Solids . . . 66·73
------
1000·00
=======
{84}
Pigment . . . . |
Bile acids . . | Organic matter . 56·73
Cholesterine . |
Sugar . . . . . |
Soda . . . . . |
Potash . . . . | Inorganic salts . 10·00
Iron . . . . . |
The difference in composition of these two biles is very striking. The
one contains more than four times as much solid matter as the other;
and if the relative amount of organic, and inorganic substances be
compared, the curious fact is observed, that the difference in the
amount of solids in the two cases, is almost entirely due to the change
in quantity of organic matter. The inorganic salts have not even so
much as doubled themselves in the abnormal bile. Whence is this? Soda
is the chief inorganic substance found in bile, and we have seen that
it occurs in the form of glycocholate, and taurocholate of soda,
substances which, as before remarked, are re-absorbed from the
distended ducts, and gall-bladder into the circulation, from whence
they are constantly being eliminated with the urine; and this, no
doubt, is one of the causes why the inorganic salts are proportionally
in such small quantity in the abnormal bile of jaundice from
obstruction.
{85} Fifthly,--In the abdomen was a considerable quantity of dark
straw-coloured serum, which on the addition of strong sulphuric acid
became of a fine emerald-green colour, in consequence of the presence
of bile. Traces of sugar were also present in the effused liquid. The
serum had only collected in the latter weeks of the patient's life, and
after the shrinking of the liver was observed to have begun.
Sixthly,--The liver was small in size, excessively dense, and very
heavy. Externally, it had a dark olive hue, and on section presented a
most curious appearance. The section was of an almost uniform
yellowish-green colour, and studded over with excavations (Plate I.,
_b_), from which thick bile streamed in all directions. The apparent
excavations were nothing more or less than immensely distended ducts.
On looking into the ducts, it was observed that they presented the
appearance of possessing valves. On microscopical examination, the
hepatic cells were found smaller than normal, as if partially
atrophied. The nuclei were unusually well marked, in consequence of the
fat granules being almost entirely absent. (Fig. 8, _b_.) In the field
of the microscope were a number of caudate or spindle-shaped cells
(Fig. 8, _c_.), from the epithelial lining of the ducts. In the hepatic
tissue were found some beautiful {86} stellate crystals, as well as a
number of separate needles of tyrosine. A few small crystals of cystine
were also found. (Fig. 8, _a_.)
[Illustration: FIG. 8.]
Seventhly,--The kidneys were enlarged, pale, and fatty-looking; and all
over the surface of the section, as well as immediately under the
capsules, which were very loosely attached, were small abscesses. The
surface was also studded with numerous minute dark bile-pigment points,
and it is possible that the abscesses were the result of the blocking
up of the capillary vessels by the pigment deposit, as previously
alluded to, page 57.
Eighthly,--The head of the pancreas was considerably enlarged, and on
cutting into it, a quantity of pus oozed out from an abscess in its
interior. The abscess was found to communicate with a large ulcerated
spot in the duodenum. (Plate I., _f_.) On microscopical examination,
the {87} tumour of the pancreas was found to consist of an hypertrophy
of the normal gland tissue, being, in fact, a chronic inflammatory
tumour of the gland substance.
In no portion of the body was a trace of cancer detected, nor any
enlargement of the mesenteric or other glands, to justify even a
suspicion of malignant disease. So the opinion arrived at regarding the
pathology of this case is, that the disease originated in an
inflammatory affection of the pancreas, during the progress of which,
the openings of the bile, and pancreatic ducts became blocked up; the
interruption to the excretion of the bile giving rise to the jaundice,
and at the same time inducing engorgement, and enlargement of the
liver. The inflammatory affection of the pancreas had probably ended in
the formation of an abscess, which, pushing the enlarged liver
forwards, admitted of the distended gall-bladder being seen, and felt
through the abdominal parietes. At length the abscess burst, and
suddenly emptied itself into the duodenum; the yellow fluid discharged
from the intestines being not bile, as the patient had supposed, but
pus. No sooner had the abscess emptied itself, than the liver returned
to its natural position, and thus accounted for the distended
gall-bladder so suddenly ceasing to be seen or felt. The ulcer in the
duodenum appears {88} to be the mouth of the abscess, which has
probably been prevented closing, partly on account of the occasional
draining away of pus, which, being in small quantity, and mixed with
the stools, escaped detection; and partly to the constant irritation of
the passage of the food, there being no bile or pancreatic fluid to
neutralize the acidity of the chyme. This might even be sufficient of
itself to delay the healing process. The ultimate gradual atrophy of
the liver would arise from the continued pressure of the distended
bile-ducts interrupting the hepatic circulation, as formerly pointed
out at page 48. Lastly, there being no bile or pancreatic juice
admitted into the intestines, the greater part of the food taken passed
out of the body unabsorbed, and the patient, though possessing an
excellent appetite, and taking plenty of food, actually died of slow
starvation.
My object in giving such prominence to this interesting case, is to
show how valuable an adjunct physiological chemistry is to the other
methods of diagnosis in obscure diseases of the abdominal organs, and
to encourage others to follow in the same path; for it must be
remembered that the foregoing was no dead-house diagnosis, but that
every fact here stated was discovered and recorded before death.
{89} Having now explained the mechanism of the two forms of
jaundice--that arising from suppression, and that induced by
obstruction--it only remains for me to remind my readers, that there is
frequently a combination of the two conditions. Jaundice from
obstruction, for example, cannot long exist without becoming
complicated with jaundice from suppression. The continued backward
pressure exerted on the hepatic parenchyma by the over-distended
bile-tubes, sooner or later impedes the circulation in the organ to an
extent sufficient to induce an impairment, if not an almost total
arrest of the biliary secretion. Hence it is, that in the last stage of
jaundice from obstruction, the biliary acids gradually diminish, and at
last finally disappear from the urine. We have it, nevertheless, in our
power to distinguish between the two forms of disease--for whereas, in
jaundice arising from simple suppression, there is only an absence of
the bile-acids; in jaundice from obstruction, complicated with
suppression, the absence of the bile-acids is usually associated with
the presence of tyrosine, and leucine. For before complete suppression
occurs as a result of obstruction, the hepatic tissue has already had
its nutrition so impaired, as to admit of the formation of these
foreign substances. Lastly, the history of the case will of itself be
an important guide.
{90} EPIDEMIC JAUNDICE.
It is seldom that jaundice attacks persons in an epidemic form; as it
does so occasionally, however, and that too in almost all countries, it
is necessary that I should say a few words on its pathology. In a
quotation, in the "Medical Times and Gazette," from the "Recueil de
Mémoires de Médecine Militaire," vol. iii. p. 374, it is stated that,
"M. Martin gave an account of an epidemic of jaundice which he had the
opportunity of observing among the artillery and engineers of the
French army stationed at Pavia during the Italian war. It commenced
during the great heats of August, and terminated by the end of October.
There occurred 71 cases in an effective of 1022 men. The causes he
considers to have been the unusual heat, which gave rise to great
congestion of the liver, the fatigue of long marches (the mounted men
suffering oftener in proportion than the unmounted), indulgence in
alcoholic drinks, and marsh miasmata. Great increase in the size of the
liver in most of the cases, and of the spleen in many, was observed,
and all complained of pain in the epigastrium and in the hypochondria.
In fact, this last was the first symptom of the approaching jaundice.
None of the cases proved fatal. Professor San-Galli {91} informed M.
Martin that a similar epidemic prevailed in the town of Pavia at the
same time."
That jaundice may also occur in an epidemic form among pregnant women,
has been shown by Dr. Saint-Vel, who relates that, "In 1858 the island
of Martinique was, without appreciable cause, visited by an epidemic of
jaundice, remarkable for its severity in pregnant women. It broke out
at St. Pierre towards the middle of April, attained its maximum height
in June and July, and terminated towards the end of the year. All races
were attacked; the patients were mostly adults; no liver-complication
could be detected; nor could any resemblance be traced between the
disease and yellow fever. It was fatal to females only, especially
during pregnancy. Of thirty pregnant women who were attacked at St.
Pierre, ten only arrived at the full period of pregnancy without
presenting any other symptoms than those of ordinary jaundice. The
other twenty all had abortion or premature labour a fortnight or three
weeks after the commencement of the attack, and died in a state of
coma, which appeared a few hours before or after the expulsion of the
foetus. The females who died were from the fourth to the eighth month
advanced in pregnancy. In some cases, slight delirium preceded the
coma, which was never interrupted, but became more and more {92}
profound up to the time of death. Its longest duration, in two cases,
was twenty-four and thirty-six hours. It was not preceded by any
notable modification of the general sensibility, nor of the respiration
or circulation. Hæmorrhage was absent, except in one case, where a
female had it before delivery. When death was delayed till three or
four days after delivery, the lochia were healthy. Almost all the
children were still-born; some lived a few hours; one alone survived.
None of the infants had the icteric colour; nor was there any sign of
jaundice in the ten children born at the full term."
The foregoing translation from the "Gazette des Hôpitaux," 20th
November 1862, appeared in the "British Medical Journal" of the 7th of
February, 1863, p. 141.
We have it further stated in the "Lancet" of the 21st February 1863,
under the head of the "Health of Rotherham," that, "scarcely had the
late fatal epidemic of fever subsided ere another, less fatal, but as
widely spread, took its place. In last November several persons were
attacked with jaundice, and now not less than 150 persons are suffering
from it. None of those who were attacked by the late fever are
suffering from the present epidemic."
When we reflect on the facts here related, we {93} can have little
difficulty in forming an opinion of the pathology of jaundice occurring
in an epidemic form. Its mechanism seems to be precisely similar to
that of the isolated cases of the disease which are every now and then
met with as the result of blood-poisoning. I have recently seen a case
of well-marked jaundice supervene on an attack of scarlet fever, and as
it affords a tolerably good illustration of the pathology of such
cases, it may, perhaps, be briefly given with advantage.
A London cabman, aged 23, was admitted under my care into University
College Hospital, on the 2nd March of the present year. He stated that
he had always enjoyed good health, but that lately he had been much out
of spirits, in consequence of the death of one of his relatives. On the
25th February, after three days' illness, a scarlatinal rash appeared
all over his chest, and extremities, and four days later (the day
before his admission), he became jaundiced. March 3rd. His skin is now
of a bright yellow colour, and when the finger is rapidly drawn across
it, a pink line immediately takes the place of the yellowness, showing
that there is still great subcutaneous vascularity. The throat is sore,
and there is considerable difficulty in swallowing. The conjunctivæ are
intensely yellow--proportionally more so than the skin, in consequence
of the scarlatinal hue being still {94} blended with the tint of the
latter. The urine is high coloured, has a slight deposit of urates;
contains a large amount of bile pigment, but no bile-acids. The stools
have not been observed to be clay-coloured. The liver is enlarged
(dulness extends 5½ inches in a perpendicular direction), and tender on
pressure. He complains of pain in the hepatic region on taking a deep
inspiration, and of a general uneasiness at other times. Has no
sickness or vomiting. The mucous membrane of the tongue is red and
raw-looking; flakes of epithelial fur are readily detached from it.
The case was at once diagnosed as one of jaundice from suppression. Its
mechanism being supposed to be identical to that of the cases discussed
at pages 25-9 under the head of jaundice arising from active congestion
of the liver induced by blood-poisoning, a dose of calomel and jalap
was accordingly administered, with the view of removing the portal
congestion, and with the most satisfactory result; for, notwithstanding
the jaundice being complicated with scarlatina, a very decided
improvement in the colour of the skin took place within twenty-four
hours, the other symptoms remaining as before. March 10th. The calomel
and jalap was repeated on the 4th, and since then the skin has
gradually become paler. It is now scarcely tinged.
{95} To return to the cases of epidemic jaundice; they, as I have just
hinted, are due to a precisely similar cause--blood-poisoning--either
the direct result of miasmata, or of contagion.
A further explanation of the reason why jaundice occurs in an epidemic
form, may be found in the circumstance that in all febrile states of
the general system some one or other of the internal organs is liable
to become congested. For example, typhus is, as a rule, complicated
with cerebral congestion, typhoid with mesenteric, ague with splenic,
scarlatina with renal, and so on. It is not, however, necessary that
the organs should be affected in the same relation to the disease as is
here given. On the contrary, in one epidemic of typhus, the brain may
be congested, in another the lungs, and in a third the liver; and so
also with other fevers. Hence we can have little difficulty in
understanding why epidemics of jaundice every now and then occur,
seeing that they are but the secondary results of other epidemic
affections, although, as occasionally happens, the jaundice is the
chief, if not the only well-marked symptom.
ARTIFICIAL JAUNDICE.
What is the source of the tyrosine, and leucine found in the urine, in
cases like those previously described? Being well aware that the
physiologist {96} has it in his power to produce almost any
pathological state or artificial disease at pleasure, I set about
imitating on an animal the effects produced in the human subject by
obstruction of the bile-ducts. Hitherto, artificial jaundice has been
usually induced either by ligaturing the gall-ducts or injecting bile
into the circulation; but as both of these methods were in the present
instance objectionable--the first on account of the constitutional
disturbance liable to be induced by the severity of the operation; the
second from the bile being all at once thrown into the circulation, and
thereby producing toxic effects, besides the danger of its too rapid
elimination by the urine--I adopted another plan, which came much
nearer to the state induced by disease in man--I took the bile of three
healthy dogs, and injected it under the skin of a fourth. In this case
the effects of the operation were almost _nil_, and the bile was at the
same time placed in a position favourable for its slow absorption, just
as in the human subject. During the first two days the animal remained
comparatively well, the urine was normal in appearance, and contained
neither bile-pigment, nor bile-acids. But on the third day the animal
became ill, and on the fourth jaundice set in. He died on the fifth.
After death the urine was found to contain not only {97} bile-pigment,
and bile-acids, but also the diseased products, leucine, and tyrosine;
and what was more interesting still, the urine was loaded with sugar,
just as occurred in the case imitated.
It will be remembered that in speaking of the bile-acids, I mentioned
that while glycocholic acid is a crystalline, taurocholic is a
non-crystalline substance. Tyrosine, and leucine stand in a similar
relation to each other; tyrosine being crystallizable, leucine
non-crystallizable. Now, taking this fact into account, together with
the fact, that when the bile-acids are allowed slowly to enter the
circulation, they reappear in the urine, accompanied with tyrosine, and
leucine; and also with the third fact of these latter substances being
found in the liver when the biliary function is interfered with, I am
inclined to look upon tyrosine, and leucine as the products either of
the arrested, or of the retrograde metamorphosis of glycocholic, and
taurocholic acids. Moreover, I have found in one case, after injecting
bile in the way before mentioned, into the cellular tissue, crystals of
tyrosine spontaneously form in the bile taken from the animal's
gall-bladder after death, and merely allowed slowly to evaporate. This
result strengthens the foregoing opinion.
Frerichs states that he has never detected the biliary acids in the
blood, even after bile had {98} been injected into the circulation. In
a remarkable case where 1 oz. of ox-bile killed a dog in less than five
minutes from the time it began to be slowly injected into the jugular
vein, I detected the bile-acids in a clear extract of the blood, with
facility. This leads me to mention that, contrary to the statement of
Frerichs, and in accordance with that of Kühne, the injection of the
pure bile-acids into the blood is very dangerous, and that even the
injection of pure bile into the cellular tissue, often proves fatal in
the course of twenty-four hours, thereby showing that the constituents
of the bile are highly poisonous.
In illustration of these facts I may cite the following experiments:--
Into the cellular tissue of the back of a full-grown, and
healthy-looking terrier dog, I injected the bile taken from the
gall-bladders of three healthy dogs, two of which had just been killed,
the other had been dead a few hours. The bile was in the first two
cases neutral, in the third faintly alkaline. All the biles seemed
perfectly normal. They contained no crystals of any kind. Eighteen
hours after the operation the animal appeared quite well, and took his
food heartily. Four hours later a remarkable change took place. The dog
looked dull and drowsy, and could not sustain himself on his legs; when
left to himself, he {99} lay on his side, and made not the slightest
movement. He was not only paralyzed, but even the nerves of sensation
had ceased to act, for when his tail, and feet were pinched, he was
quite insensible to pain. The pupils were dilated, and the body felt
cold. Death occurred twenty-three hours after the operation. Urine, and
fæces were passed in small quantity immediately before death. The urine
was strongly alkaline, and effervesced on the addition of sulphuric
acid, thereby showing that it contained alkaline carbonates. Prismatic
phosphatic crystals were present in the still fresh urine.
When tested for bile-acids, only the faintest trace was obtained, after
the urine had been cleared with the acetate of lead and sulphuretted
hydrogen.
The tissues of the abdomen and thorax were oedematous, but, within an
hour after death, had not the disagreeable odour found in animals
killed by injecting pure bile-acid. (_See_ foot-note at p. 39.)
This experiment was again repeated with alkaline bile. Two ounces of
ox-bile of a specific gravity of 1025 were injected under the skin of a
large pointer dog. In twenty-four hours the animal was dead; the
sub-cutaneous tissue all round the seat of the injection, red,
inflamed, and infiltrated with {100} blood. The urinary bladder was
empty. The gall-bladder contained 1½ ounces of dark bile of a specific
gravity of 1040. When examined with the microscope, the blood was found
to contain a large excess of white corpuscles.[26]
[Footnote 26: It has just been said that the blood contained a large
amount of white blood corpuscles. This reminds me of a fact that I have
omitted to mention--namely, that in a case of severe jaundice from
suppression, in consequence of cirrhosis of the liver, I found that the
blood possessed a very treacle-like aspect. The serum was of a dingy
yellow hue, and felt somewhat sticky to the fingers. Under the
microscope the blood corpuscles were found to be large, and flabby, had
a great tendency to adhere together by the edges, and become flattened
on the sides whenever they came in contact. Moreover, the corpuscles
looked as if they had no distinct cell-wall; some, and that too, in the
freshly drawn blood, gave off buds, others split into two, each half
when separate looking like a distinct blood corpuscle. In fact, the
blood looked more as if it had been acted upon by some powerful
chemical agent than anything else. I again examined it after the death
of the patient, and found it presented all the above characters in a
still more marked degree. To the naked eye it had a viscid, tarry
appearance.]
These results rather militate against the theory of the bile being
re-absorbed, in an unchanged state, into the circulation, after the
completion of the digestive process.
{101} TREATMENT OF JAUNDICE.
After what has been said regarding the pathology of jaundice, I need
scarcely remark that the treatment must vary according to the kind of
disorder we have to deal with. A line of treatment found to be
beneficial in one case of jaundice, might prove very hurtful in
another. For, as has been shown in the foregoing pages, jaundice from
suppression, and jaundice from obstruction, are, it might be said, two
entirely different diseases, with only the symptoms of yellow skin,
high-coloured urine, and pipe-clay stools in common. The success of our
treatment will therefore depend on our powers of diagnosis.
The general principles upon which the treatment of jaundice must be
founded are as follows:--